{"id":"0","document_id":"227508","passages":[{"id":"1","type":"title","text":["Naloxone reverses the antihypertensive effect of clonidine."],"offsets":[[0,59]]},{"id":"2","type":"abstract","text":["In unanesthetized, spontaneously hypertensive rats the decrease in blood pressure and heart rate produced by intravenous clonidine, 5 to 20 micrograms\/kg, was inhibited or reversed by nalozone, 0.2 to 2 mg\/kg. The hypotensive effect of 100 mg\/kg alpha-methyldopa was also partially reversed by naloxone. Naloxone alone did not affect either blood pressure or heart rate. In brain membranes from spontaneously hypertensive rats clonidine, 10(-8) to 10(-5) M, did not influence stereoselective binding of [3H]-naloxone (8 nM), and naloxone, 10(-8) to 10(-4) M, did not influence clonidine-suppressible binding of [3H]-dihydroergocryptine (1 nM). These findings indicate that in spontaneously hypertensive rats the effects of central alpha-adrenoceptor stimulation involve activation of opiate receptors. As naloxone and clonidine do not appear to interact with the same receptor site, the observed functional antagonism suggests the release of an endogenous opiate by clonidine or alpha-methyldopa and the possible role of the opiate in the central control of sympathetic tone."],"offsets":[[60,1135]]}],"entities":[{"id":"3","type":"Chemical","text":["Naloxone"],"offsets":[[0,8]],"normalized":[{"db_name":"MESH","db_id":"D009270"}]},{"id":"4","type":"Chemical","text":["clonidine"],"offsets":[[49,58]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]},{"id":"5","type":"Disease","text":["hypertensive"],"offsets":[[93,105]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"6","type":"Chemical","text":["clonidine"],"offsets":[[181,190]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]},{"id":"7","type":"Chemical","text":["nalozone"],"offsets":[[244,252]],"normalized":[]},{"id":"8","type":"Disease","text":["hypotensive"],"offsets":[[274,285]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"9","type":"Chemical","text":["alpha-methyldopa"],"offsets":[[306,322]],"normalized":[{"db_name":"MESH","db_id":"D008750"}]},{"id":"10","type":"Chemical","text":["naloxone"],"offsets":[[354,362]],"normalized":[{"db_name":"MESH","db_id":"D009270"}]},{"id":"11","type":"Chemical","text":["Naloxone"],"offsets":[[364,372]],"normalized":[{"db_name":"MESH","db_id":"D009270"}]},{"id":"12","type":"Disease","text":["hypertensive"],"offsets":[[469,481]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"13","type":"Chemical","text":["clonidine"],"offsets":[[487,496]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]},{"id":"14","type":"Chemical","text":["[3H]-naloxone"],"offsets":[[563,576]],"normalized":[]},{"id":"15","type":"Chemical","text":["naloxone"],"offsets":[[589,597]],"normalized":[{"db_name":"MESH","db_id":"D009270"}]},{"id":"16","type":"Chemical","text":["clonidine"],"offsets":[[637,646]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]},{"id":"17","type":"Chemical","text":["[3H]-dihydroergocryptine"],"offsets":[[671,695]],"normalized":[]},{"id":"18","type":"Disease","text":["hypertensive"],"offsets":[[750,762]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"19","type":"Chemical","text":["naloxone"],"offsets":[[865,873]],"normalized":[{"db_name":"MESH","db_id":"D009270"}]},{"id":"20","type":"Chemical","text":["clonidine"],"offsets":[[878,887]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]},{"id":"21","type":"Chemical","text":["clonidine"],"offsets":[[1026,1035]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]},{"id":"22","type":"Chemical","text":["alpha-methyldopa"],"offsets":[[1039,1055]],"normalized":[{"db_name":"MESH","db_id":"D008750"}]}],"events":[],"coreferences":[],"relations":[{"id":"23","type":"CID","arg1_id":"9","arg2_id":"8","normalized":[]},{"id":"24","type":"CID","arg1_id":"22","arg2_id":"8","normalized":[]}]}
{"id":"25","document_id":"354896","passages":[{"id":"26","type":"title","text":["Lidocaine-induced cardiac asystole."],"offsets":[[0,35]]},{"id":"27","type":"abstract","text":["Intravenous administration of a single 50-mg bolus of lidocaine in a 67-year-old man resulted in profound depression of the activity of the sinoatrial and atrioventricular nodal pacemakers. The patient had no apparent associated conditions which might have predisposed him to the development of bradyarrhythmias; and, thus, this probably represented a true idiosyncrasy to lidocaine."],"offsets":[[36,419]]}],"entities":[{"id":"28","type":"Chemical","text":["Lidocaine"],"offsets":[[0,9]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"29","type":"Disease","text":["cardiac asystole"],"offsets":[[18,34]],"normalized":[{"db_name":"MESH","db_id":"D006323"}]},{"id":"30","type":"Chemical","text":["lidocaine"],"offsets":[[90,99]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"31","type":"Disease","text":["depression"],"offsets":[[142,152]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"32","type":"Disease","text":["bradyarrhythmias"],"offsets":[[331,347]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"33","type":"Chemical","text":["lidocaine"],"offsets":[[409,418]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]}],"events":[],"coreferences":[],"relations":[{"id":"34","type":"CID","arg1_id":"28","arg2_id":"29","normalized":[]},{"id":"35","type":"CID","arg1_id":"30","arg2_id":"29","normalized":[]},{"id":"36","type":"CID","arg1_id":"33","arg2_id":"29","normalized":[]}]}
{"id":"37","document_id":"435349","passages":[{"id":"38","type":"title","text":["Suxamethonium infusion rate and observed fasciculations. A dose-response study."],"offsets":[[0,79]]},{"id":"39","type":"abstract","text":["Suxamethonium chloride (Sch) was administered i.v. to 36 adult males at six rates: 0.25 mg s-1 to 20 mg s-1. The infusion was discontinued either when there was no muscular response to tetanic stimulation of the ulnar nerve or when Sch 120 mg was exceeded. Six additional patients received a 30-mg i.v. bolus dose. Fasciculations in six areas of the body were scored from 0 to 3 and summated as a total fasciculation score. The times to first fasciculation, twitch suppression and tetanus suppression were inversely related to the infusion rates. Fasciculations in the six areas and the total fasciculation score were related directly to the rate of infusion. Total fasciculation scores in the 30-mg bolus group and the 5-mg s-1 and 20-mg s-1 infusion groups were not significantly different."],"offsets":[[80,872]]}],"entities":[{"id":"40","type":"Chemical","text":["Suxamethonium"],"offsets":[[0,13]],"normalized":[{"db_name":"MESH","db_id":"D013390"}]},{"id":"41","type":"Disease","text":["fasciculations"],"offsets":[[41,55]],"normalized":[{"db_name":"MESH","db_id":"D005207"}]},{"id":"42","type":"Chemical","text":["Suxamethonium chloride"],"offsets":[[80,102]],"normalized":[{"db_name":"MESH","db_id":"D013390"}]},{"id":"43","type":"Chemical","text":["Sch"],"offsets":[[104,107]],"normalized":[{"db_name":"MESH","db_id":"D013390"}]},{"id":"44","type":"Disease","text":["tetanic"],"offsets":[[265,272]],"normalized":[{"db_name":"MESH","db_id":"D013746"}]},{"id":"45","type":"Chemical","text":["Sch"],"offsets":[[312,315]],"normalized":[{"db_name":"MESH","db_id":"D013390"}]},{"id":"46","type":"Disease","text":["Fasciculations"],"offsets":[[395,409]],"normalized":[{"db_name":"MESH","db_id":"D005207"}]},{"id":"47","type":"Disease","text":["fasciculation"],"offsets":[[483,496]],"normalized":[{"db_name":"MESH","db_id":"D005207"}]},{"id":"48","type":"Disease","text":["fasciculation"],"offsets":[[523,536]],"normalized":[{"db_name":"MESH","db_id":"D005207"}]},{"id":"49","type":"Disease","text":["twitch"],"offsets":[[538,544]],"normalized":[{"db_name":"MESH","db_id":"D013746"}]},{"id":"50","type":"Disease","text":["tetanus"],"offsets":[[561,568]],"normalized":[{"db_name":"MESH","db_id":"D013746"}]},{"id":"51","type":"Disease","text":["Fasciculations"],"offsets":[[627,641]],"normalized":[{"db_name":"MESH","db_id":"D005207"}]},{"id":"52","type":"Disease","text":["fasciculation"],"offsets":[[673,686]],"normalized":[{"db_name":"MESH","db_id":"D005207"}]},{"id":"53","type":"Disease","text":["fasciculation"],"offsets":[[746,759]],"normalized":[{"db_name":"MESH","db_id":"D005207"}]}],"events":[],"coreferences":[],"relations":[{"id":"54","type":"CID","arg1_id":"40","arg2_id":"41","normalized":[]},{"id":"55","type":"CID","arg1_id":"40","arg2_id":"46","normalized":[]},{"id":"56","type":"CID","arg1_id":"40","arg2_id":"47","normalized":[]},{"id":"57","type":"CID","arg1_id":"40","arg2_id":"48","normalized":[]},{"id":"58","type":"CID","arg1_id":"40","arg2_id":"51","normalized":[]},{"id":"59","type":"CID","arg1_id":"40","arg2_id":"52","normalized":[]},{"id":"60","type":"CID","arg1_id":"40","arg2_id":"53","normalized":[]},{"id":"61","type":"CID","arg1_id":"42","arg2_id":"41","normalized":[]},{"id":"62","type":"CID","arg1_id":"42","arg2_id":"46","normalized":[]},{"id":"63","type":"CID","arg1_id":"42","arg2_id":"47","normalized":[]},{"id":"64","type":"CID","arg1_id":"42","arg2_id":"48","normalized":[]},{"id":"65","type":"CID","arg1_id":"42","arg2_id":"51","normalized":[]},{"id":"66","type":"CID","arg1_id":"42","arg2_id":"52","normalized":[]},{"id":"67","type":"CID","arg1_id":"42","arg2_id":"53","normalized":[]},{"id":"68","type":"CID","arg1_id":"43","arg2_id":"41","normalized":[]},{"id":"69","type":"CID","arg1_id":"43","arg2_id":"46","normalized":[]},{"id":"70","type":"CID","arg1_id":"43","arg2_id":"47","normalized":[]},{"id":"71","type":"CID","arg1_id":"43","arg2_id":"48","normalized":[]},{"id":"72","type":"CID","arg1_id":"43","arg2_id":"51","normalized":[]},{"id":"73","type":"CID","arg1_id":"43","arg2_id":"52","normalized":[]},{"id":"74","type":"CID","arg1_id":"43","arg2_id":"53","normalized":[]},{"id":"75","type":"CID","arg1_id":"45","arg2_id":"41","normalized":[]},{"id":"76","type":"CID","arg1_id":"45","arg2_id":"46","normalized":[]},{"id":"77","type":"CID","arg1_id":"45","arg2_id":"47","normalized":[]},{"id":"78","type":"CID","arg1_id":"45","arg2_id":"48","normalized":[]},{"id":"79","type":"CID","arg1_id":"45","arg2_id":"51","normalized":[]},{"id":"80","type":"CID","arg1_id":"45","arg2_id":"52","normalized":[]},{"id":"81","type":"CID","arg1_id":"45","arg2_id":"53","normalized":[]}]}
{"id":"82","document_id":"603022","passages":[{"id":"83","type":"title","text":["Galanthamine hydrobromide, a longer acting anticholinesterase drug, in the treatment of the central effects of scopolamine (Hyoscine)."],"offsets":[[0,134]]},{"id":"84","type":"abstract","text":["Galanthamine hydrobromide, an anticholinesterase drug capable of penetrating the blood-brain barrier, was used in a patient demonstrating central effects of scopolamine (hyoscine) overdosage. It is longer acting than physostigmine and is used in anaesthesia to reverse the non-depolarizing neuromuscular block. However, studies into the dose necessary to combating scopolamine intoxication are indicated."],"offsets":[[135,539]]}],"entities":[{"id":"85","type":"Chemical","text":["Galanthamine hydrobromide"],"offsets":[[0,25]],"normalized":[{"db_name":"MESH","db_id":"D005702"}]},{"id":"86","type":"Chemical","text":["scopolamine"],"offsets":[[111,122]],"normalized":[{"db_name":"MESH","db_id":"D012601"}]},{"id":"87","type":"Chemical","text":["Hyoscine"],"offsets":[[124,132]],"normalized":[{"db_name":"MESH","db_id":"D012601"}]},{"id":"88","type":"Chemical","text":["Galanthamine hydrobromide"],"offsets":[[135,160]],"normalized":[{"db_name":"MESH","db_id":"D005702"}]},{"id":"89","type":"Chemical","text":["scopolamine"],"offsets":[[292,303]],"normalized":[{"db_name":"MESH","db_id":"D012601"}]},{"id":"90","type":"Chemical","text":["hyoscine"],"offsets":[[305,313]],"normalized":[{"db_name":"MESH","db_id":"D012601"}]},{"id":"91","type":"Disease","text":["overdosage"],"offsets":[[315,325]],"normalized":[{"db_name":"MESH","db_id":"D062787"}]},{"id":"92","type":"Chemical","text":["physostigmine"],"offsets":[[352,365]],"normalized":[{"db_name":"MESH","db_id":"D010830"}]},{"id":"93","type":"Chemical","text":["scopolamine"],"offsets":[[500,511]],"normalized":[{"db_name":"MESH","db_id":"D012601"}]}],"events":[],"coreferences":[],"relations":[{"id":"94","type":"CID","arg1_id":"86","arg2_id":"91","normalized":[]},{"id":"95","type":"CID","arg1_id":"87","arg2_id":"91","normalized":[]},{"id":"96","type":"CID","arg1_id":"89","arg2_id":"91","normalized":[]},{"id":"97","type":"CID","arg1_id":"90","arg2_id":"91","normalized":[]},{"id":"98","type":"CID","arg1_id":"93","arg2_id":"91","normalized":[]}]}
{"id":"99","document_id":"1378968","passages":[{"id":"100","type":"title","text":["Effects of uninephrectomy and high protein feeding on lithium-induced chronic renal failure in rats."],"offsets":[[0,100]]},{"id":"101","type":"abstract","text":["Rats with lithium-induced nephropathy were subjected to high protein (HP) feeding, uninephrectomy (NX) or a combination of these, in an attempt to induce glomerular hyperfiltration and further progression of renal failure. Newborn female Wistar rats were fed a lithium-containing diet (50 mmol\/kg) for 8 weeks and then randomized to normal diet, HP diet (40 vs. 19%), NX or HP+NX for another 8 weeks. Corresponding non-lithium pretreated groups were generated. When comparing all lithium treated versus non-lithium-treated groups, lithium caused a reduction in glomerular filtration rate (GFR) without significant changes in effective renal plasma flow (as determined by a marker secreted into the proximal tubules) or lithium clearance. Consequently, lithium pretreatment caused a fall in filtration fraction and an increase in fractional Li excretion. Lithium also caused proteinuria and systolic hypertension in absence of glomerulosclerosis. HP failed to accentuante progression of renal failure and in fact tended to increase GFR and decrease plasma creatinine levels in lithium pretreated rats. NX caused an additive deterioration in GFR which, however, was ameliorated by HP. NX+HP caused a further rise in blood pressure in Li-pretreated rats. The results indicate that Li-induced nephropathy, even when the GFR is only modestly reduced, is associated with proteinuria and arterial systolic hypertension. In this model of chronic renal failure the decline in GFR is not accompanied by a corresponding fall in effective renal plasma flow, which may be the functional expression of the formation of nonfiltrating atubular glomeruli. The fractional reabsorption of tubular fluid by the proximal tubules is reduced, leaving the distal delivery unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)"],"offsets":[[101,1892]]}],"entities":[{"id":"102","type":"Chemical","text":["lithium"],"offsets":[[54,61]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"103","type":"Disease","text":["chronic renal failure"],"offsets":[[70,91]],"normalized":[{"db_name":"MESH","db_id":"D007676"}]},{"id":"104","type":"Chemical","text":["lithium"],"offsets":[[111,118]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"105","type":"Disease","text":["nephropathy"],"offsets":[[127,138]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"106","type":"Disease","text":["renal 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{"id":"212","document_id":"1420741","passages":[{"id":"213","type":"title","text":["Treatment of Crohn's disease with fusidic acid: an antibiotic with immunosuppressive properties similar to cyclosporin."],"offsets":[[0,119]]},{"id":"214","type":"abstract","text":["Fusidic acid is an antibiotic with T-cell specific immunosuppressive effects similar to those of cyclosporin. Because of the need for the development of new treatments for Crohn's disease, a pilot study was undertaken to estimate the pharmacodynamics and tolerability of fusidic acid treatment in chronic active, therapy-resistant patients. Eight Crohn's disease patients were included. Fusidic acid was administered orally in a dose of 500 mg t.d.s. and the treatment was planned to last 8 weeks. The disease activity was primarily measured by a modified individual grading score. Five of 8 patients (63%) improved during fusidic acid treatment: 3 at two weeks and 2 after four weeks. There were no serious clinical side effects, but dose reduction was required in two patients because of nausea. Biochemically, an increase in alkaline phosphatases was noted in 5 of 8 cases (63%), and the greatest increases were seen in those who had elevated levels prior to treatment. All reversed to pre-treatment levels after cessation of treatment. The results of this pilot study suggest that fusidic acid may be of benefit in selected chronic active Crohn's disease patients in whom conventional treatment is ineffective. Because there seems to exist a scientific rationale for the use of fusidic acid at the cytokine level in inflammatory bowel disease, we suggest that the role of this treatment should be further investigated."],"offsets":[[120,1542]]}],"entities":[{"id":"215","type":"Disease","text":["Crohn's disease"],"offsets":[[13,28]],"normalized":[{"db_name":"MESH","db_id":"D003424"}]},{"id":"216","type":"Chemical","text":["fusidic acid"],"offsets":[[34,46]],"normalized":[{"db_name":"MESH","db_id":"D005672"}]},{"id":"217","type":"Chemical","text":["cyclosporin"],"offsets":[[107,118]],"normalized":[{"db_name":"MESH","db_id":"D016572"}]},{"id":"218","type":"Chemical","text":["cyclosporin"],"offsets":[[217,228]],"normalized":[{"db_name":"MESH","db_id":"D016572"}]},{"id":"219","type":"Disease","text":["Crohn's disease"],"offsets":[[292,307]],"normalized":[{"db_name":"MESH","db_id":"D003424"}]},{"id":"220","type":"Chemical","text":["fusidic acid"],"offsets":[[391,403]],"normalized":[{"db_name":"MESH","db_id":"D005672"}]},{"id":"221","type":"Disease","text":["Crohn's disease"],"offsets":[[467,482]],"normalized":[{"db_name":"MESH","db_id":"D003424"}]},{"id":"222","type":"Chemical","text":["Fusidic acid"],"offsets":[[507,519]],"normalized":[{"db_name":"MESH","db_id":"D005672"}]},{"id":"223","type":"Chemical","text":["fusidic acid"],"offsets":[[743,755]],"normalized":[{"db_name":"MESH","db_id":"D005672"}]},{"id":"224","type":"Disease","text":["nausea"],"offsets":[[910,916]],"normalized":[{"db_name":"MESH","db_id":"D009325"}]},{"id":"225","type":"Chemical","text":["fusidic acid"],"offsets":[[1205,1217]],"normalized":[{"db_name":"MESH","db_id":"D005672"}]},{"id":"226","type":"Disease","text":["Crohn's disease"],"offsets":[[1263,1278]],"normalized":[{"db_name":"MESH","db_id":"D003424"}]},{"id":"227","type":"Chemical","text":["fusidic acid"],"offsets":[[1402,1414]],"normalized":[{"db_name":"MESH","db_id":"D005672"}]},{"id":"228","type":"Disease","text":["inflammatory bowel disease"],"offsets":[[1440,1466]],"normalized":[{"db_name":"MESH","db_id":"D015212"}]}],"events":[],"coreferences":[],"relations":[{"id":"229","type":"CID","arg1_id":"216","arg2_id":"224","normalized":[]},{"id":"230","type":"CID","arg1_id":"220","arg2_id":"224","normalized":[]},{"id":"231","type":"CID","arg1_id":"222","arg2_id":"224","normalized":[]},{"id":"232","type":"CID","arg1_id":"223","arg2_id":"224","normalized":[]},{"id":"233","type":"CID","arg1_id":"225","arg2_id":"224","normalized":[]},{"id":"234","type":"CID","arg1_id":"227","arg2_id":"224","normalized":[]}]}
{"id":"235","document_id":"1601297","passages":[{"id":"236","type":"title","text":["Electrocardiographic evidence of myocardial injury in psychiatrically hospitalized cocaine abusers."],"offsets":[[0,99]]},{"id":"237","type":"abstract","text":["The electrocardiograms (ECG) of 99 cocaine-abusing patients were compared with the ECGs of 50 schizophrenic controls. Eleven of the cocaine abusers and none of the controls had ECG evidence of significant myocardial injury defined as myocardial infarction, ischemia, and bundle branch block."],"offsets":[[100,391]]}],"entities":[{"id":"238","type":"Disease","text":["myocardial injury"],"offsets":[[33,50]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"239","type":"Chemical","text":["cocaine"],"offsets":[[83,90]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"240","type":"Chemical","text":["cocaine"],"offsets":[[135,142]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"241","type":"Disease","text":["schizophrenic"],"offsets":[[194,207]],"normalized":[{"db_name":"MESH","db_id":"D012559"}]},{"id":"242","type":"Chemical","text":["cocaine"],"offsets":[[232,239]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"243","type":"Disease","text":["myocardial injury"],"offsets":[[305,322]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"244","type":"Disease","text":["myocardial infarction"],"offsets":[[334,355]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"245","type":"Disease","text":["ischemia"],"offsets":[[357,365]],"normalized":[{"db_name":"MESH","db_id":"D007511"}]},{"id":"246","type":"Disease","text":["bundle branch block"],"offsets":[[371,390]],"normalized":[{"db_name":"MESH","db_id":"D002037"}]}],"events":[],"coreferences":[],"relations":[{"id":"247","type":"CID","arg1_id":"239","arg2_id":"244","normalized":[]},{"id":"248","type":"CID","arg1_id":"240","arg2_id":"244","normalized":[]},{"id":"249","type":"CID","arg1_id":"242","arg2_id":"244","normalized":[]},{"id":"250","type":"CID","arg1_id":"239","arg2_id":"246","normalized":[]},{"id":"251","type":"CID","arg1_id":"240","arg2_id":"246","normalized":[]},{"id":"252","type":"CID","arg1_id":"242","arg2_id":"246","normalized":[]}]}
{"id":"253","document_id":"1967484","passages":[{"id":"254","type":"title","text":["Sulpiride-induced tardive dystonia."],"offsets":[[0,35]]},{"id":"255","type":"abstract","text":["Sulpiride is a selective D2-receptor antagonist with antipsychotic and antidepressant properties. Although initially thought to be free of extrapyramidal side effects, sulpiride-induced tardive dyskinesia and parkinsonism have been reported occasionally. We studied a 37-year-old man who developed persistent segmental dystonia within 2 months after starting sulpiride therapy. We could not find any previous reports of sulpiride-induced tardive dystonia."],"offsets":[[36,491]]}],"entities":[{"id":"256","type":"Chemical","text":["Sulpiride"],"offsets":[[0,9]],"normalized":[{"db_name":"MESH","db_id":"D013469"}]},{"id":"257","type":"Disease","text":["tardive dystonia"],"offsets":[[18,34]],"normalized":[{"db_name":"MESH","db_id":"D004421"}]},{"id":"258","type":"Chemical","text":["Sulpiride"],"offsets":[[36,45]],"normalized":[{"db_name":"MESH","db_id":"D013469"}]},{"id":"259","type":"Chemical","text":["antidepressant"],"offsets":[[107,121]],"normalized":[{"db_name":"MESH","db_id":"D000928"}]},{"id":"260","type":"Chemical","text":["sulpiride"],"offsets":[[204,213]],"normalized":[{"db_name":"MESH","db_id":"D013469"}]},{"id":"261","type":"Disease","text":["tardive dyskinesia"],"offsets":[[222,240]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"262","type":"Disease","text":["parkinsonism"],"offsets":[[245,257]],"normalized":[{"db_name":"MESH","db_id":"D010302"}]},{"id":"263","type":"Disease","text":["dystonia"],"offsets":[[355,363]],"normalized":[{"db_name":"MESH","db_id":"D004421"}]},{"id":"264","type":"Chemical","text":["sulpiride"],"offsets":[[395,404]],"normalized":[{"db_name":"MESH","db_id":"D013469"}]},{"id":"265","type":"Chemical","text":["sulpiride"],"offsets":[[456,465]],"normalized":[{"db_name":"MESH","db_id":"D013469"}]},{"id":"266","type":"Disease","text":["tardive dystonia"],"offsets":[[474,490]],"normalized":[{"db_name":"MESH","db_id":"D004421"}]}],"events":[],"coreferences":[],"relations":[{"id":"267","type":"CID","arg1_id":"256","arg2_id":"257","normalized":[]},{"id":"268","type":"CID","arg1_id":"256","arg2_id":"263","normalized":[]},{"id":"269","type":"CID","arg1_id":"256","arg2_id":"266","normalized":[]},{"id":"270","type":"CID","arg1_id":"258","arg2_id":"257","normalized":[]},{"id":"271","type":"CID","arg1_id":"258","arg2_id":"263","normalized":[]},{"id":"272","type":"CID","arg1_id":"258","arg2_id":"266","normalized":[]},{"id":"273","type":"CID","arg1_id":"260","arg2_id":"257","normalized":[]},{"id":"274","type":"CID","arg1_id":"260","arg2_id":"263","normalized":[]},{"id":"275","type":"CID","arg1_id":"260","arg2_id":"266","normalized":[]},{"id":"276","type":"CID","arg1_id":"264","arg2_id":"257","normalized":[]},{"id":"277","type":"CID","arg1_id":"264","arg2_id":"263","normalized":[]},{"id":"278","type":"CID","arg1_id":"264","arg2_id":"266","normalized":[]},{"id":"279","type":"CID","arg1_id":"265","arg2_id":"257","normalized":[]},{"id":"280","type":"CID","arg1_id":"265","arg2_id":"263","normalized":[]},{"id":"281","type":"CID","arg1_id":"265","arg2_id":"266","normalized":[]}]}
{"id":"282","document_id":"2234245","passages":[{"id":"283","type":"title","text":["Ocular and auditory toxicity in hemodialyzed patients receiving desferrioxamine."],"offsets":[[0,80]]},{"id":"284","type":"abstract","text":["During an 18-month period of study 41 hemodialyzed patients receiving desferrioxamine (10-40 mg\/kg BW\/3 times weekly) for the first time were monitored for detection of audiovisual toxicity. 6 patients presented clinical symptoms of visual or auditory toxicity. Moreover, detailed ophthalmologic and audiologic studies disclosed abnormalities in 7 more asymptomatic patients. Visual toxicity was of retinal origin and was characterized by a tritan-type dyschromatopsy, sometimes associated with a loss of visual acuity and pigmentary retinal deposits. Auditory toxicity was characterized by a mid- to high-frequency neurosensorial hearing loss and the lesion was of the cochlear type. Desferrioxamine withdrawal resulted in a complete recovery of visual function in 1 patient and partial recovery in 3, and a complete reversal of hearing loss in 3 patients and partial recovery in 3. This toxicity appeared in patients receiving the higher doses of desferrioxamine or coincided with the normalization of ferritin or aluminium serum levels. The data indicate that audiovisual toxicity is not an infrequent complication in hemodialyzed patients receiving desferrioxamine. Periodical audiovisual monitoring should be performed on hemodialyzed patients receiving the drug in order to detect adverse effects as early as possible."],"offsets":[[81,1405]]}],"entities":[{"id":"285","type":"Disease","text":["Ocular and auditory toxicity"],"offsets":[[0,28]],"normalized":[{"db_name":"MESH","db_id":"D014786"},{"db_name":"MESH","db_id":"D006311"}]},{"id":"286","type":"Disease","text":["Ocular","toxicity"],"offsets":[[0,6],[20,28]],"normalized":[{"db_name":"MESH","db_id":"D014786"}]},{"id":"287","type":"Disease","text":["auditory toxicity"],"offsets":[[11,28]],"normalized":[{"db_name":"MESH","db_id":"D006311"}]},{"id":"288","type":"Chemical","text":["desferrioxamine"],"offsets":[[64,79]],"normalized":[{"db_name":"MESH","db_id":"D003676"}]},{"id":"289","type":"Chemical","text":["desferrioxamine"],"offsets":[[151,166]],"normalized":[{"db_name":"MESH","db_id":"D003676"}]},{"id":"290","type":"Disease","text":["audiovisual 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{"id":"357","document_id":"2385256","passages":[{"id":"358","type":"title","text":["Myasthenia gravis presenting as weakness after magnesium administration."],"offsets":[[0,72]]},{"id":"359","type":"abstract","text":["We studied a patient with no prior history of neuromuscular disease who became virtually quadriplegic after parenteral magnesium administration for preeclampsia. The serum magnesium concentration was 3.0 mEq\/L, which is usually well tolerated. The magnesium was stopped and she recovered over a few days. While she was weak, 2-Hz repetitive stimulation revealed a decrement without significant facilitation at rapid rates or after exercise, suggesting postsynaptic neuromuscular blockade. After her strength returned, repetitive stimulation was normal, but single fiber EMG revealed increased jitter and blocking. Her acetylcholine receptor antibody level was markedly elevated. Although paralysis after magnesium administration has been described in patients with known myasthenia gravis, it has not previously been reported to be the initial or only manifestation of the disease. Patients who are unusually sensitive to the neuromuscular effects of magnesium should be suspected of having an underlying disorder of neuromuscular transmission."],"offsets":[[73,1117]]}],"entities":[{"id":"360","type":"Disease","text":["Myasthenia gravis"],"offsets":[[0,17]],"normalized":[{"db_name":"MESH","db_id":"D009157"}]},{"id":"361","type":"Chemical","text":["magnesium"],"offsets":[[47,56]],"normalized":[{"db_name":"MESH","db_id":"D008274"}]},{"id":"362","type":"Disease","text":["neuromuscular disease"],"offsets":[[119,140]],"normalized":[{"db_name":"MESH","db_id":"D009468"}]},{"id":"363","type":"Disease","text":["quadriplegic"],"offsets":[[162,174]],"normalized":[{"db_name":"MESH","db_id":"D011782"}]},{"id":"364","type":"Chemical","text":["magnesium"],"offsets":[[192,201]],"normalized":[{"db_name":"MESH","db_id":"D008274"}]},{"id":"365","type":"Disease","text":["preeclampsia"],"offsets":[[221,233]],"normalized":[{"db_name":"MESH","db_id":"D011225"}]},{"id":"366","type":"Chemical","text":["magnesium"],"offsets":[[245,254]],"normalized":[{"db_name":"MESH","db_id":"D008274"}]},{"id":"367","type":"Chemical","text":["magnesium"],"offsets":[[321,330]],"normalized":[{"db_name":"MESH","db_id":"D008274"}]},{"id":"368","type":"Disease","text":["postsynaptic neuromuscular blockade"],"offsets":[[525,560]],"normalized":[{"db_name":"MESH","db_id":"D009468"}]},{"id":"369","type":"Chemical","text":["acetylcholine"],"offsets":[[691,704]],"normalized":[{"db_name":"MESH","db_id":"D000109"}]},{"id":"370","type":"Disease","text":["paralysis"],"offsets":[[761,770]],"normalized":[{"db_name":"MESH","db_id":"D010243"}]},{"id":"371","type":"Chemical","text":["magnesium"],"offsets":[[777,786]],"normalized":[{"db_name":"MESH","db_id":"D008274"}]},{"id":"372","type":"Disease","text":["myasthenia gravis"],"offsets":[[844,861]],"normalized":[{"db_name":"MESH","db_id":"D009157"}]},{"id":"373","type":"Chemical","text":["magnesium"],"offsets":[[1024,1033]],"normalized":[{"db_name":"MESH","db_id":"D008274"}]},{"id":"374","type":"Disease","text":["disorder of neuromuscular transmission"],"offsets":[[1078,1116]],"normalized":[{"db_name":"MESH","db_id":"D020511"}]}],"events":[],"coreferences":[],"relations":[{"id":"375","type":"CID","arg1_id":"361","arg2_id":"360","normalized":[]},{"id":"376","type":"CID","arg1_id":"361","arg2_id":"372","normalized":[]},{"id":"377","type":"CID","arg1_id":"364","arg2_id":"360","normalized":[]},{"id":"378","type":"CID","arg1_id":"364","arg2_id":"372","normalized":[]},{"id":"379","type":"CID","arg1_id":"366","arg2_id":"360","normalized":[]},{"id":"380","type":"CID","arg1_id":"366","arg2_id":"372","normalized":[]},{"id":"381","type":"CID","arg1_id":"367","arg2_id":"360","normalized":[]},{"id":"382","type":"CID","arg1_id":"367","arg2_id":"372","normalized":[]},{"id":"383","type":"CID","arg1_id":"371","arg2_id":"360","normalized":[]},{"id":"384","type":"CID","arg1_id":"371","arg2_id":"372","normalized":[]},{"id":"385","type":"CID","arg1_id":"373","arg2_id":"360","normalized":[]},{"id":"386","type":"CID","arg1_id":"373","arg2_id":"372","normalized":[]}]}
{"id":"387","document_id":"2505783","passages":[{"id":"388","type":"title","text":["Chloroacetaldehyde and its contribution to urotoxicity during treatment with cyclophosphamide or ifosfamide. An experimental study\/short communication."],"offsets":[[0,151]]},{"id":"389","type":"abstract","text":["Based on clinical data, indicating that chloroacetaldehyde (CAA) is an important metabolite of oxazaphosphorine cytostatics, an experimental study was carried out in order to elucidate the role of CAA in the development of hemorrhagic cystitis. The data demonstrate that CAA after i.v. administration does not contribute to bladder damage. When instilled directly into the bladder, CAA exerts urotoxic effects, it is, however, susceptible to detoxification with mesna."],"offsets":[[152,620]]}],"entities":[{"id":"390","type":"Chemical","text":["Chloroacetaldehyde"],"offsets":[[0,18]],"normalized":[{"db_name":"MESH","db_id":"C004656"}]},{"id":"391","type":"Chemical","text":["cyclophosphamide"],"offsets":[[77,93]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"392","type":"Chemical","text":["ifosfamide"],"offsets":[[97,107]],"normalized":[{"db_name":"MESH","db_id":"D007069"}]},{"id":"393","type":"Chemical","text":["chloroacetaldehyde"],"offsets":[[192,210]],"normalized":[{"db_name":"MESH","db_id":"C004656"}]},{"id":"394","type":"Chemical","text":["CAA"],"offsets":[[212,215]],"normalized":[{"db_name":"MESH","db_id":"C004656"}]},{"id":"395","type":"Chemical","text":["CAA"],"offsets":[[349,352]],"normalized":[{"db_name":"MESH","db_id":"C004656"}]},{"id":"396","type":"Disease","text":["hemorrhagic cystitis"],"offsets":[[375,395]],"normalized":[{"db_name":"MESH","db_id":"D006470"},{"db_name":"MESH","db_id":"D003556"}]},{"id":"397","type":"Disease","text":["hemorrhagic"],"offsets":[[375,386]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"398","type":"Disease","text":["cystitis"],"offsets":[[387,395]],"normalized":[{"db_name":"MESH","db_id":"D003556"}]},{"id":"399","type":"Chemical","text":["CAA"],"offsets":[[423,426]],"normalized":[{"db_name":"MESH","db_id":"C004656"}]},{"id":"400","type":"Disease","text":["bladder damage"],"offsets":[[476,490]],"normalized":[{"db_name":"MESH","db_id":"D001745"}]},{"id":"401","type":"Chemical","text":["CAA"],"offsets":[[534,537]],"normalized":[{"db_name":"MESH","db_id":"C004656"}]},{"id":"402","type":"Chemical","text":["mesna"],"offsets":[[614,619]],"normalized":[{"db_name":"MESH","db_id":"D015080"}]}],"events":[],"coreferences":[],"relations":[{"id":"403","type":"CID","arg1_id":"390","arg2_id":"396","normalized":[]},{"id":"404","type":"CID","arg1_id":"390","arg2_id":"398","normalized":[]},{"id":"405","type":"CID","arg1_id":"393","arg2_id":"396","normalized":[]},{"id":"406","type":"CID","arg1_id":"393","arg2_id":"398","normalized":[]},{"id":"407","type":"CID","arg1_id":"394","arg2_id":"396","normalized":[]},{"id":"408","type":"CID","arg1_id":"394","arg2_id":"398","normalized":[]},{"id":"409","type":"CID","arg1_id":"395","arg2_id":"396","normalized":[]},{"id":"410","type":"CID","arg1_id":"395","arg2_id":"398","normalized":[]},{"id":"411","type":"CID","arg1_id":"399","arg2_id":"396","normalized":[]},{"id":"412","type":"CID","arg1_id":"399","arg2_id":"398","normalized":[]},{"id":"413","type":"CID","arg1_id":"401","arg2_id":"396","normalized":[]},{"id":"414","type":"CID","arg1_id":"401","arg2_id":"398","normalized":[]},{"id":"415","type":"CID","arg1_id":"390","arg2_id":"396","normalized":[]},{"id":"416","type":"CID","arg1_id":"390","arg2_id":"397","normalized":[]},{"id":"417","type":"CID","arg1_id":"393","arg2_id":"396","normalized":[]},{"id":"418","type":"CID","arg1_id":"393","arg2_id":"397","normalized":[]},{"id":"419","type":"CID","arg1_id":"394","arg2_id":"396","normalized":[]},{"id":"420","type":"CID","arg1_id":"394","arg2_id":"397","normalized":[]},{"id":"421","type":"CID","arg1_id":"395","arg2_id":"396","normalized":[]},{"id":"422","type":"CID","arg1_id":"395","arg2_id":"397","normalized":[]},{"id":"423","type":"CID","arg1_id":"399","arg2_id":"396","normalized":[]},{"id":"424","type":"CID","arg1_id":"399","arg2_id":"397","normalized":[]},{"id":"425","type":"CID","arg1_id":"401","arg2_id":"396","normalized":[]},{"id":"426","type":"CID","arg1_id":"401","arg2_id":"397","normalized":[]}]}
{"id":"427","document_id":"2515254","passages":[{"id":"428","type":"title","text":["Source of pain and primitive dysfunction in migraine: an identical site?"],"offsets":[[0,72]]},{"id":"429","type":"abstract","text":["Twenty common migraine patients received a one sided frontotemporal application of nitroglycerin (10 patients) or placebo ointment (10 patients) in a double blind study. Early onset migraine attacks were induced by nitroglycerin in seven out of 10 patients versus no patient in the placebo group. Subsequently 20 migraine patients, who developed an early onset attack with frontotemporal nitroglycerin, received the drug in a second induction test at other body areas. No early onset migraine was observed. Thus the migraine-inducing effect of nitroglycerin seems to depend on direct stimulation of the habitual site of pain, suggesting that the frontotemporal region is of crucial importance in the development of a migraine crisis. This is not consistent with a CNS origin of migraine attack."],"offsets":[[73,867]]}],"entities":[{"id":"430","type":"Disease","text":["pain"],"offsets":[[10,14]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"431","type":"Disease","text":["migraine"],"offsets":[[44,52]],"normalized":[{"db_name":"MESH","db_id":"D008881"}]},{"id":"432","type":"Disease","text":["migraine"],"offsets":[[87,95]],"normalized":[{"db_name":"MESH","db_id":"D008881"}]},{"id":"433","type":"Chemical","text":["nitroglycerin"],"offsets":[[156,169]],"normalized":[{"db_name":"MESH","db_id":"D005996"}]},{"id":"434","type":"Disease","text":["migraine"],"offsets":[[255,263]],"normalized":[{"db_name":"MESH","db_id":"D008881"}]},{"id":"435","type":"Chemical","text":["nitroglycerin"],"offsets":[[288,301]],"normalized":[{"db_name":"MESH","db_id":"D005996"}]},{"id":"436","type":"Disease","text":["migraine"],"offsets":[[386,394]],"normalized":[{"db_name":"MESH","db_id":"D008881"}]},{"id":"437","type":"Chemical","text":["nitroglycerin"],"offsets":[[461,474]],"normalized":[{"db_name":"MESH","db_id":"D005996"}]},{"id":"438","type":"Disease","text":["migraine"],"offsets":[[557,565]],"normalized":[{"db_name":"MESH","db_id":"D008881"}]},{"id":"439","type":"Disease","text":["migraine"],"offsets":[[589,597]],"normalized":[{"db_name":"MESH","db_id":"D008881"}]},{"id":"440","type":"Chemical","text":["nitroglycerin"],"offsets":[[617,630]],"normalized":[{"db_name":"MESH","db_id":"D005996"}]},{"id":"441","type":"Disease","text":["pain"],"offsets":[[693,697]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"442","type":"Disease","text":["migraine"],"offsets":[[790,798]],"normalized":[{"db_name":"MESH","db_id":"D008881"}]},{"id":"443","type":"Disease","text":["migraine"],"offsets":[[851,859]],"normalized":[{"db_name":"MESH","db_id":"D008881"}]}],"events":[],"coreferences":[],"relations":[{"id":"444","type":"CID","arg1_id":"433","arg2_id":"431","normalized":[]},{"id":"445","type":"CID","arg1_id":"433","arg2_id":"432","normalized":[]},{"id":"446","type":"CID","arg1_id":"433","arg2_id":"434","normalized":[]},{"id":"447","type":"CID","arg1_id":"433","arg2_id":"436","normalized":[]},{"id":"448","type":"CID","arg1_id":"433","arg2_id":"438","normalized":[]},{"id":"449","type":"CID","arg1_id":"433","arg2_id":"439","normalized":[]},{"id":"450","type":"CID","arg1_id":"433","arg2_id":"442","normalized":[]},{"id":"451","type":"CID","arg1_id":"433","arg2_id":"443","normalized":[]},{"id":"452","type":"CID","arg1_id":"435","arg2_id":"431","normalized":[]},{"id":"453","type":"CID","arg1_id":"435","arg2_id":"432","normalized":[]},{"id":"454","type":"CID","arg1_id":"435","arg2_id":"434","normalized":[]},{"id":"455","type":"CID","arg1_id":"435","arg2_id":"436","normalized":[]},{"id":"456","type":"CID","arg1_id":"435","arg2_id":"438","normalized":[]},{"id":"457","type":"CID","arg1_id":"435","arg2_id":"439","normalized":[]},{"id":"458","type":"CID","arg1_id":"435","arg2_id":"442","normalized":[]},{"id":"459","type":"CID","arg1_id":"435","arg2_id":"443","normalized":[]},{"id":"460","type":"CID","arg1_id":"437","arg2_id":"431","normalized":[]},{"id":"461","type":"CID","arg1_id":"437","arg2_id":"432","normalized":[]},{"id":"462","type":"CID","arg1_id":"437","arg2_id":"434","normalized":[]},{"id":"463","type":"CID","arg1_id":"437","arg2_id":"436","normalized":[]},{"id":"464","type":"CID","arg1_id":"437","arg2_id":"438","normalized":[]},{"id":"465","type":"CID","arg1_id":"437","arg2_id":"439","normalized":[]},{"id":"466","type":"CID","arg1_id":"437","arg2_id":"442","normalized":[]},{"id":"467","type":"CID","arg1_id":"437","arg2_id":"443","normalized":[]},{"id":"468","type":"CID","arg1_id":"440","arg2_id":"431","normalized":[]},{"id":"469","type":"CID","arg1_id":"440","arg2_id":"432","normalized":[]},{"id":"470","type":"CID","arg1_id":"440","arg2_id":"434","normalized":[]},{"id":"471","type":"CID","arg1_id":"440","arg2_id":"436","normalized":[]},{"id":"472","type":"CID","arg1_id":"440","arg2_id":"438","normalized":[]},{"id":"473","type":"CID","arg1_id":"440","arg2_id":"439","normalized":[]},{"id":"474","type":"CID","arg1_id":"440","arg2_id":"442","normalized":[]},{"id":"475","type":"CID","arg1_id":"440","arg2_id":"443","normalized":[]}]}
{"id":"476","document_id":"2572625","passages":[{"id":"477","type":"title","text":["Clotiazepam-induced acute hepatitis."],"offsets":[[0,36]]},{"id":"478","type":"abstract","text":["We report the case of a patient who developed acute hepatitis with extensive hepatocellular necrosis, 7 months after the onset of administration of clotiazepam, a thienodiazepine derivative. Clotiazepam withdrawal was followed by prompt recovery. The administration of several benzodiazepines, chemically related to clotiazepam, did not interfere with recovery and did not induce any relapse of hepatitis. This observation shows that clotiazepam can induce acute hepatitis and suggests that there is no cross hepatotoxicity between clotiazepam and several benzodiazepines."],"offsets":[[37,609]]}],"entities":[{"id":"479","type":"Chemical","text":["Clotiazepam"],"offsets":[[0,11]],"normalized":[{"db_name":"MESH","db_id":"C084599"}]},{"id":"480","type":"Disease","text":["hepatitis"],"offsets":[[26,35]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"481","type":"Disease","text":["hepatitis"],"offsets":[[89,98]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"482","type":"Disease","text":["extensive hepatocellular necrosis"],"offsets":[[104,137]],"normalized":[{"db_name":"MESH","db_id":"D047508"}]},{"id":"483","type":"Chemical","text":["clotiazepam"],"offsets":[[185,196]],"normalized":[{"db_name":"MESH","db_id":"C084599"}]},{"id":"484","type":"Chemical","text":["thienodiazepine"],"offsets":[[200,215]],"normalized":[{"db_name":"MESH","db_id":"C013295"}]},{"id":"485","type":"Chemical","text":["Clotiazepam"],"offsets":[[228,239]],"normalized":[{"db_name":"MESH","db_id":"C084599"}]},{"id":"486","type":"Chemical","text":["benzodiazepines"],"offsets":[[314,329]],"normalized":[{"db_name":"MESH","db_id":"D001569"}]},{"id":"487","type":"Chemical","text":["clotiazepam"],"offsets":[[353,364]],"normalized":[{"db_name":"MESH","db_id":"C084599"}]},{"id":"488","type":"Disease","text":["hepatitis"],"offsets":[[432,441]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"489","type":"Chemical","text":["clotiazepam"],"offsets":[[471,482]],"normalized":[{"db_name":"MESH","db_id":"C084599"}]},{"id":"490","type":"Disease","text":["hepatitis"],"offsets":[[500,509]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"491","type":"Disease","text":["hepatotoxicity"],"offsets":[[546,560]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"492","type":"Chemical","text":["clotiazepam"],"offsets":[[569,580]],"normalized":[{"db_name":"MESH","db_id":"C084599"}]},{"id":"493","type":"Chemical","text":["benzodiazepines"],"offsets":[[593,608]],"normalized":[{"db_name":"MESH","db_id":"D001569"}]}],"events":[],"coreferences":[],"relations":[{"id":"494","type":"CID","arg1_id":"479","arg2_id":"480","normalized":[]},{"id":"495","type":"CID","arg1_id":"479","arg2_id":"481","normalized":[]},{"id":"496","type":"CID","arg1_id":"479","arg2_id":"488","normalized":[]},{"id":"497","type":"CID","arg1_id":"479","arg2_id":"490","normalized":[]},{"id":"498","type":"CID","arg1_id":"479","arg2_id":"491","normalized":[]},{"id":"499","type":"CID","arg1_id":"483","arg2_id":"480","normalized":[]},{"id":"500","type":"CID","arg1_id":"483","arg2_id":"481","normalized":[]},{"id":"501","type":"CID","arg1_id":"483","arg2_id":"488","normalized":[]},{"id":"502","type":"CID","arg1_id":"483","arg2_id":"490","normalized":[]},{"id":"503","type":"CID","arg1_id":"483","arg2_id":"491","normalized":[]},{"id":"504","type":"CID","arg1_id":"485","arg2_id":"480","normalized":[]},{"id":"505","type":"CID","arg1_id":"485","arg2_id":"481","normalized":[]},{"id":"506","type":"CID","arg1_id":"485","arg2_id":"488","normalized":[]},{"id":"507","type":"CID","arg1_id":"485","arg2_id":"490","normalized":[]},{"id":"508","type":"CID","arg1_id":"485","arg2_id":"491","normalized":[]},{"id":"509","type":"CID","arg1_id":"487","arg2_id":"480","normalized":[]},{"id":"510","type":"CID","arg1_id":"487","arg2_id":"481","normalized":[]},{"id":"511","type":"CID","arg1_id":"487","arg2_id":"488","normalized":[]},{"id":"512","type":"CID","arg1_id":"487","arg2_id":"490","normalized":[]},{"id":"513","type":"CID","arg1_id":"487","arg2_id":"491","normalized":[]},{"id":"514","type":"CID","arg1_id":"489","arg2_id":"480","normalized":[]},{"id":"515","type":"CID","arg1_id":"489","arg2_id":"481","normalized":[]},{"id":"516","type":"CID","arg1_id":"489","arg2_id":"488","normalized":[]},{"id":"517","type":"CID","arg1_id":"489","arg2_id":"490","normalized":[]},{"id":"518","type":"CID","arg1_id":"489","arg2_id":"491","normalized":[]},{"id":"519","type":"CID","arg1_id":"492","arg2_id":"480","normalized":[]},{"id":"520","type":"CID","arg1_id":"492","arg2_id":"481","normalized":[]},{"id":"521","type":"CID","arg1_id":"492","arg2_id":"488","normalized":[]},{"id":"522","type":"CID","arg1_id":"492","arg2_id":"490","normalized":[]},{"id":"523","type":"CID","arg1_id":"492","arg2_id":"491","normalized":[]}]}
{"id":"524","document_id":"2632720","passages":[{"id":"525","type":"title","text":["Arterial hypertension as a complication of prolonged ketoconazole treatment."],"offsets":[[0,76]]},{"id":"526","type":"abstract","text":["Two of 14 patients with Cushing's syndrome treated on a long-term basis with ketoconazole developed sustained hypertension. In both cases normal plasma and urinary free cortisol levels had been achieved following ketoconazole therapy, yet continuous blood pressure monitoring demonstrated hypertension 31 (patient 1) and 52 weeks (patient 2) after treatment. In patient 1, plasma levels of deoxycorticosterone and 11-deoxycortisol were elevated. In patient 2, in addition to an increase in both deoxycorticosterone and 11-deoxycortisol levels, plasma aldosterone values were raised, with a concomitant suppression of renin levels. Our findings show that long-term treatment with high doses of ketoconazole may induce enzyme blockade leading to mineralocorticoid-related hypertension."],"offsets":[[77,860]]}],"entities":[{"id":"527","type":"Disease","text":["hypertension"],"offsets":[[9,21]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"528","type":"Chemical","text":["ketoconazole"],"offsets":[[53,65]],"normalized":[{"db_name":"MESH","db_id":"D007654"}]},{"id":"529","type":"Disease","text":["Cushing's syndrome"],"offsets":[[101,119]],"normalized":[{"db_name":"MESH","db_id":"D003480"}]},{"id":"530","type":"Chemical","text":["ketoconazole"],"offsets":[[154,166]],"normalized":[{"db_name":"MESH","db_id":"D007654"}]},{"id":"531","type":"Disease","text":["hypertension"],"offsets":[[187,199]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"532","type":"Chemical","text":["cortisol"],"offsets":[[246,254]],"normalized":[{"db_name":"MESH","db_id":"D006854"}]},{"id":"533","type":"Chemical","text":["ketoconazole"],"offsets":[[290,302]],"normalized":[{"db_name":"MESH","db_id":"D007654"}]},{"id":"534","type":"Disease","text":["hypertension"],"offsets":[[366,378]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"535","type":"Chemical","text":["deoxycorticosterone"],"offsets":[[467,486]],"normalized":[{"db_name":"MESH","db_id":"D003900"}]},{"id":"536","type":"Chemical","text":["11-deoxycortisol"],"offsets":[[491,507]],"normalized":[{"db_name":"MESH","db_id":"D003350"}]},{"id":"537","type":"Chemical","text":["deoxycorticosterone"],"offsets":[[572,591]],"normalized":[{"db_name":"MESH","db_id":"D003900"}]},{"id":"538","type":"Chemical","text":["11-deoxycortisol"],"offsets":[[596,612]],"normalized":[{"db_name":"MESH","db_id":"D003350"}]},{"id":"539","type":"Chemical","text":["aldosterone"],"offsets":[[628,639]],"normalized":[{"db_name":"MESH","db_id":"D000450"}]},{"id":"540","type":"Chemical","text":["ketoconazole"],"offsets":[[770,782]],"normalized":[{"db_name":"MESH","db_id":"D007654"}]},{"id":"541","type":"Disease","text":["hypertension"],"offsets":[[847,859]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]}],"events":[],"coreferences":[],"relations":[{"id":"542","type":"CID","arg1_id":"528","arg2_id":"527","normalized":[]},{"id":"543","type":"CID","arg1_id":"528","arg2_id":"531","normalized":[]},{"id":"544","type":"CID","arg1_id":"528","arg2_id":"534","normalized":[]},{"id":"545","type":"CID","arg1_id":"528","arg2_id":"541","normalized":[]},{"id":"546","type":"CID","arg1_id":"530","arg2_id":"527","normalized":[]},{"id":"547","type":"CID","arg1_id":"530","arg2_id":"531","normalized":[]},{"id":"548","type":"CID","arg1_id":"530","arg2_id":"534","normalized":[]},{"id":"549","type":"CID","arg1_id":"530","arg2_id":"541","normalized":[]},{"id":"550","type":"CID","arg1_id":"533","arg2_id":"527","normalized":[]},{"id":"551","type":"CID","arg1_id":"533","arg2_id":"531","normalized":[]},{"id":"552","type":"CID","arg1_id":"533","arg2_id":"534","normalized":[]},{"id":"553","type":"CID","arg1_id":"533","arg2_id":"541","normalized":[]},{"id":"554","type":"CID","arg1_id":"540","arg2_id":"527","normalized":[]},{"id":"555","type":"CID","arg1_id":"540","arg2_id":"531","normalized":[]},{"id":"556","type":"CID","arg1_id":"540","arg2_id":"534","normalized":[]},{"id":"557","type":"CID","arg1_id":"540","arg2_id":"541","normalized":[]}]}
{"id":"558","document_id":"2670794","passages":[{"id":"559","type":"title","text":["Effects of an inhibitor of angiotensin converting enzyme (Captopril) on pulmonary and renal insufficiency due to intravascular coagulation in the rat."],"offsets":[[0,150]]},{"id":"560","type":"abstract","text":["Induction of intravascular coagulation and inhibition of fibrinolysis by injection of thrombin and tranexamic acid (AMCA) in the rat gives rise to pulmonary and renal insufficiency resembling that occurring after trauma or sepsis in man. Injection of Captopril (1 mg\/kg), an inhibitor of angiotensin converting enzyme (ACE), reduced both pulmonary and renal insufficiency in this rat model. The lung weights were lower and PaO2 was improved in rats given this enzyme-blocking agent. The contents of albumin in the lungs were not changed, indicating that Captopril did not influence the extravasation of protein. Renal damage as reflected by an increase in serum urea and in kidney weight was prevented by Captopril. The amount of fibrin in the kidneys was also considerably lower than in animals which received thrombin and AMCA alone. It is suggested that the effects of Captopril on the lungs may be attributable to a vasodilatory effect due to a reduction in the circulating level of Angiotension II and an increase in prostacyclin (secondary to an increase in bradykinin). Captopril may, by the same mechanism, reduce the increase in glomerular filtration that is known to occur after an injection of thrombin, thereby diminishing the aggregation of fibrin monomers in the glomeruli, with the result that less fibrin will be deposited and thus less kidney damage will be produced."],"offsets":[[151,1535]]}],"entities":[{"id":"561","type":"Chemical","text":["angiotensin"],"offsets":[[27,38]],"normalized":[{"db_name":"MESH","db_id":"D000809"}]},{"id":"562","type":"Chemical","text":["Captopril"],"offsets":[[58,67]],"normalized":[{"db_name":"MESH","db_id":"D002216"}]},{"id":"563","type":"Disease","text":["pulmonary and renal insufficiency"],"offsets":[[72,105]],"normalized":[{"db_name":"MESH","db_id":"D011665"},{"db_name":"MESH","db_id":"D051437"}]},{"id":"564","type":"Disease","text":["pulmonary","insufficiency"],"offsets":[[72,81],[92,105]],"normalized":[{"db_name":"MESH","db_id":"D011665"}]},{"id":"565","type":"Disease","text":["renal insufficiency"],"offsets":[[86,105]],"normalized":[{"db_name":"MESH","db_id":"D051437"}]},{"id":"566","type":"Disease","text":["intravascular coagulation"],"offsets":[[113,138]],"normalized":[{"db_name":"MESH","db_id":"D004211"}]},{"id":"567","type":"Disease","text":["intravascular coagulation"],"offsets":[[164,189]],"normalized":[{"db_name":"MESH","db_id":"D004211"}]},{"id":"568","type":"Chemical","text":["tranexamic acid"],"offsets":[[250,265]],"normalized":[{"db_name":"MESH","db_id":"D014148"}]},{"id":"569","type":"Chemical","text":["AMCA"],"offsets":[[267,271]],"normalized":[{"db_name":"MESH","db_id":"D014148"}]},{"id":"570","type":"Disease","text":["pulmonary and renal insufficiency"],"offsets":[[298,331]],"normalized":[{"db_name":"MESH","db_id":"D011665"},{"db_name":"MESH","db_id":"D051437"}]},{"id":"571","type":"Disease","text":["pulmonary","insufficiency"],"offsets":[[298,307],[318,331]],"normalized":[{"db_name":"MESH","db_id":"D011665"}]},{"id":"572","type":"Disease","text":["renal insufficiency"],"offsets":[[312,331]],"normalized":[{"db_name":"MESH","db_id":"D051437"}]},{"id":"573","type":"Disease","text":["trauma"],"offsets":[[364,370]],"normalized":[{"db_name":"MESH","db_id":"D014947"}]},{"id":"574","type":"Disease","text":["sepsis"],"offsets":[[374,380]],"normalized":[{"db_name":"MESH","db_id":"D018805"}]},{"id":"575","type":"Chemical","text":["Captopril"],"offsets":[[402,411]],"normalized":[{"db_name":"MESH","db_id":"D002216"}]},{"id":"576","type":"Chemical","text":["angiotensin"],"offsets":[[439,450]],"normalized":[{"db_name":"MESH","db_id":"D000809"}]},{"id":"577","type":"Disease","text":["pulmonary and renal insufficiency"],"offsets":[[489,522]],"normalized":[{"db_name":"MESH","db_id":"D011665"},{"db_name":"MESH","db_id":"D051437"}]},{"id":"578","type":"Disease","text":["pulmonary","insufficiency"],"offsets":[[489,498],[509,522]],"normalized":[{"db_name":"MESH","db_id":"D011665"}]},{"id":"579","type":"Disease","text":["renal insufficiency"],"offsets":[[503,522]],"normalized":[{"db_name":"MESH","db_id":"D051437"}]},{"id":"580","type":"Chemical","text":["Captopril"],"offsets":[[705,714]],"normalized":[{"db_name":"MESH","db_id":"D002216"}]},{"id":"581","type":"Disease","text":["Renal damage"],"offsets":[[763,775]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"582","type":"Chemical","text":["urea"],"offsets":[[813,817]],"normalized":[{"db_name":"MESH","db_id":"D014508"}]},{"id":"583","type":"Chemical","text":["Captopril"],"offsets":[[856,865]],"normalized":[{"db_name":"MESH","db_id":"D002216"}]},{"id":"584","type":"Chemical","text":["AMCA"],"offsets":[[975,979]],"normalized":[{"db_name":"MESH","db_id":"D014148"}]},{"id":"585","type":"Chemical","text":["Captopril"],"offsets":[[1023,1032]],"normalized":[{"db_name":"MESH","db_id":"D002216"}]},{"id":"586","type":"Chemical","text":["Angiotension II"],"offsets":[[1138,1153]],"normalized":[{"db_name":"MESH","db_id":"D000804"}]},{"id":"587","type":"Chemical","text":["prostacyclin"],"offsets":[[1173,1185]],"normalized":[{"db_name":"MESH","db_id":"D011464"}]},{"id":"588","type":"Chemical","text":["bradykinin"],"offsets":[[1215,1225]],"normalized":[{"db_name":"MESH","db_id":"D001920"}]},{"id":"589","type":"Chemical","text":["Captopril"],"offsets":[[1228,1237]],"normalized":[{"db_name":"MESH","db_id":"D002216"}]},{"id":"590","type":"Disease","text":["kidney damage"],"offsets":[[1504,1517]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]}],"events":[],"coreferences":[],"relations":[{"id":"591","type":"CID","arg1_id":"568","arg2_id":"566","normalized":[]},{"id":"592","type":"CID","arg1_id":"568","arg2_id":"567","normalized":[]},{"id":"593","type":"CID","arg1_id":"569","arg2_id":"566","normalized":[]},{"id":"594","type":"CID","arg1_id":"569","arg2_id":"567","normalized":[]},{"id":"595","type":"CID","arg1_id":"584","arg2_id":"566","normalized":[]},{"id":"596","type":"CID","arg1_id":"584","arg2_id":"567","normalized":[]}]}
{"id":"597","document_id":"2696505","passages":[{"id":"598","type":"title","text":["A randomized comparison of labetalol and nitroprusside for induced hypotension."],"offsets":[[0,79]]},{"id":"599","type":"abstract","text":["In a randomized study, labetalol-induced hypotension and nitroprusside-induced hypotension were compared in 20 patients (10 in each group) scheduled for major orthopedic procedures. Each patient was subjected to an identical anesthetic protocol and similar drug-induced reductions in mean arterial blood pressure (BP) (50 to 55 mmHg). Nitroprusside infusion was associated with a significant (p less than 0.05) increase in heart rate and cardiac output; rebound hypertension was observed in three patients after discontinuation of nitroprusside. Labetalol administration was not associated with any of these findings. Arterial PO2 decreased in both groups. It was concluded that labetalol offers advantages over nitroprusside."],"offsets":[[80,806]]}],"entities":[{"id":"600","type":"Chemical","text":["labetalol"],"offsets":[[27,36]],"normalized":[{"db_name":"MESH","db_id":"D007741"}]},{"id":"601","type":"Chemical","text":["nitroprusside"],"offsets":[[41,54]],"normalized":[{"db_name":"MESH","db_id":"D009599"}]},{"id":"602","type":"Disease","text":["hypotension"],"offsets":[[67,78]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"603","type":"Chemical","text":["labetalol"],"offsets":[[103,112]],"normalized":[{"db_name":"MESH","db_id":"D007741"}]},{"id":"604","type":"Disease","text":["hypotension"],"offsets":[[121,132]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"605","type":"Chemical","text":["nitroprusside"],"offsets":[[137,150]],"normalized":[{"db_name":"MESH","db_id":"D009599"}]},{"id":"606","type":"Disease","text":["hypotension"],"offsets":[[159,170]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"607","type":"Disease","text":["reductions in mean arterial blood pressure"],"offsets":[[350,392]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"608","type":"Disease","text":["increase in heart rate and cardiac output"],"offsets":[[491,532]],"normalized":[{"db_name":"MESH","db_id":"D016534"}]},{"id":"609","type":"Disease","text":["hypertension"],"offsets":[[542,554]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"610","type":"Chemical","text":["nitroprusside"],"offsets":[[611,624]],"normalized":[{"db_name":"MESH","db_id":"D009599"}]},{"id":"611","type":"Chemical","text":["Labetalol"],"offsets":[[626,635]],"normalized":[{"db_name":"MESH","db_id":"D007741"}]},{"id":"612","type":"Chemical","text":["PO2"],"offsets":[[707,710]],"normalized":[{"db_name":"MESH","db_id":"C093415"}]},{"id":"613","type":"Chemical","text":["labetalol"],"offsets":[[759,768]],"normalized":[{"db_name":"MESH","db_id":"D007741"}]},{"id":"614","type":"Chemical","text":["nitroprusside"],"offsets":[[792,805]],"normalized":[{"db_name":"MESH","db_id":"D009599"}]}],"events":[],"coreferences":[],"relations":[{"id":"615","type":"CID","arg1_id":"601","arg2_id":"602","normalized":[]},{"id":"616","type":"CID","arg1_id":"601","arg2_id":"604","normalized":[]},{"id":"617","type":"CID","arg1_id":"601","arg2_id":"606","normalized":[]},{"id":"618","type":"CID","arg1_id":"601","arg2_id":"607","normalized":[]},{"id":"619","type":"CID","arg1_id":"605","arg2_id":"602","normalized":[]},{"id":"620","type":"CID","arg1_id":"605","arg2_id":"604","normalized":[]},{"id":"621","type":"CID","arg1_id":"605","arg2_id":"606","normalized":[]},{"id":"622","type":"CID","arg1_id":"605","arg2_id":"607","normalized":[]},{"id":"623","type":"CID","arg1_id":"610","arg2_id":"602","normalized":[]},{"id":"624","type":"CID","arg1_id":"610","arg2_id":"604","normalized":[]},{"id":"625","type":"CID","arg1_id":"610","arg2_id":"606","normalized":[]},{"id":"626","type":"CID","arg1_id":"610","arg2_id":"607","normalized":[]},{"id":"627","type":"CID","arg1_id":"614","arg2_id":"602","normalized":[]},{"id":"628","type":"CID","arg1_id":"614","arg2_id":"604","normalized":[]},{"id":"629","type":"CID","arg1_id":"614","arg2_id":"606","normalized":[]},{"id":"630","type":"CID","arg1_id":"614","arg2_id":"607","normalized":[]},{"id":"631","type":"CID","arg1_id":"601","arg2_id":"608","normalized":[]},{"id":"632","type":"CID","arg1_id":"605","arg2_id":"608","normalized":[]},{"id":"633","type":"CID","arg1_id":"610","arg2_id":"608","normalized":[]},{"id":"634","type":"CID","arg1_id":"614","arg2_id":"608","normalized":[]},{"id":"635","type":"CID","arg1_id":"600","arg2_id":"602","normalized":[]},{"id":"636","type":"CID","arg1_id":"600","arg2_id":"604","normalized":[]},{"id":"637","type":"CID","arg1_id":"600","arg2_id":"606","normalized":[]},{"id":"638","type":"CID","arg1_id":"600","arg2_id":"607","normalized":[]},{"id":"639","type":"CID","arg1_id":"603","arg2_id":"602","normalized":[]},{"id":"640","type":"CID","arg1_id":"603","arg2_id":"604","normalized":[]},{"id":"641","type":"CID","arg1_id":"603","arg2_id":"606","normalized":[]},{"id":"642","type":"CID","arg1_id":"603","arg2_id":"607","normalized":[]},{"id":"643","type":"CID","arg1_id":"611","arg2_id":"602","normalized":[]},{"id":"644","type":"CID","arg1_id":"611","arg2_id":"604","normalized":[]},{"id":"645","type":"CID","arg1_id":"611","arg2_id":"606","normalized":[]},{"id":"646","type":"CID","arg1_id":"611","arg2_id":"607","normalized":[]},{"id":"647","type":"CID","arg1_id":"613","arg2_id":"602","normalized":[]},{"id":"648","type":"CID","arg1_id":"613","arg2_id":"604","normalized":[]},{"id":"649","type":"CID","arg1_id":"613","arg2_id":"606","normalized":[]},{"id":"650","type":"CID","arg1_id":"613","arg2_id":"607","normalized":[]}]}
{"id":"651","document_id":"2924746","passages":[{"id":"652","type":"title","text":["Chronic carbamazepine treatment in the rat: efficacy, toxicity, and effect on plasma and tissue folate concentrations."],"offsets":[[0,118]]},{"id":"653","type":"abstract","text":["Folate depletion has often been a problem in chronic antiepileptic drug (AED) therapy. Carbamazepine (CBZ), a commonly used AED, has been implicated in some clinical studies. A rat model was developed to examine the effects of chronic CBZ treatment on folate concentrations in the rat. In the course of developing this model, a common vehicle, propylene glycol, by itself in high doses, was found to exhibit protective properties against induced seizures and inhibited weight gain. Seizures induced by hexafluorodiethyl ether (HFDE) were also found to be a more sensitive measure of protection by CBZ than seizures induced by maximal electroshock (MES). Oral administration of CBZ as an aqueous suspension every 8 h at a dose of 250 mg\/kg was continuously protective against HFDE-induced seizures and was minimally toxic as measured by weight gain over 8 weeks of treatment. The CBZ levels measured in plasma and brain of these animals, however, were below those normally considered protective. This treatment with CBZ had no apparent adverse effect on folate concentrations in the rat, and, indeed, the folate concentration increased in liver after 6 weeks of treatment and in plasma at 8 weeks of treatment."],"offsets":[[119,1328]]}],"entities":[{"id":"654","type":"Chemical","text":["carbamazepine"],"offsets":[[8,21]],"normalized":[{"db_name":"MESH","db_id":"D002220"}]},{"id":"655","type":"Disease","text":["toxicity"],"offsets":[[54,62]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"656","type":"Chemical","text":["folate"],"offsets":[[96,102]],"normalized":[{"db_name":"MESH","db_id":"D005492"}]},{"id":"657","type":"Chemical","text":["Folate"],"offsets":[[119,125]],"normalized":[{"db_name":"MESH","db_id":"D005492"}]},{"id":"658","type":"Chemical","text":["Carbamazepine"],"offsets":[[206,219]],"normalized":[{"db_name":"MESH","db_id":"D002220"}]},{"id":"659","type":"Chemical","text":["CBZ"],"offsets":[[221,224]],"normalized":[{"db_name":"MESH","db_id":"D002220"}]},{"id":"660","type":"Chemical","text":["CBZ"],"offsets":[[354,357]],"normalized":[{"db_name":"MESH","db_id":"D002220"}]},{"id":"661","type":"Chemical","text":["folate"],"offsets":[[371,377]],"normalized":[{"db_name":"MESH","db_id":"D005492"}]},{"id":"662","type":"Chemical","text":["propylene glycol"],"offsets":[[463,479]],"normalized":[{"db_name":"MESH","db_id":"D019946"}]},{"id":"663","type":"Disease","text":["seizures"],"offsets":[[565,573]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"664","type":"Disease","text":["weight gain"],"offsets":[[588,599]],"normalized":[{"db_name":"MESH","db_id":"D015430"}]},{"id":"665","type":"Disease","text":["Seizures"],"offsets":[[601,609]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"666","type":"Chemical","text":["hexafluorodiethyl ether"],"offsets":[[621,644]],"normalized":[{"db_name":"MESH","db_id":"D005481"}]},{"id":"667","type":"Chemical","text":["HFDE"],"offsets":[[646,650]],"normalized":[{"db_name":"MESH","db_id":"D005481"}]},{"id":"668","type":"Chemical","text":["CBZ"],"offsets":[[716,719]],"normalized":[{"db_name":"MESH","db_id":"D002220"}]},{"id":"669","type":"Disease","text":["seizures"],"offsets":[[725,733]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"670","type":"Chemical","text":["CBZ"],"offsets":[[796,799]],"normalized":[{"db_name":"MESH","db_id":"D002220"}]},{"id":"671","type":"Chemical","text":["HFDE"],"offsets":[[894,898]],"normalized":[{"db_name":"MESH","db_id":"D005481"}]},{"id":"672","type":"Disease","text":["seizures"],"offsets":[[907,915]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"673","type":"Disease","text":["weight gain"],"offsets":[[955,966]],"normalized":[{"db_name":"MESH","db_id":"D015430"}]},{"id":"674","type":"Chemical","text":["CBZ"],"offsets":[[998,1001]],"normalized":[{"db_name":"MESH","db_id":"D002220"}]},{"id":"675","type":"Chemical","text":["CBZ"],"offsets":[[1134,1137]],"normalized":[{"db_name":"MESH","db_id":"D002220"}]},{"id":"676","type":"Chemical","text":["folate"],"offsets":[[1172,1178]],"normalized":[{"db_name":"MESH","db_id":"D005492"}]},{"id":"677","type":"Chemical","text":["folate"],"offsets":[[1223,1229]],"normalized":[{"db_name":"MESH","db_id":"D005492"}]}],"events":[],"coreferences":[],"relations":[{"id":"678","type":"CID","arg1_id":"666","arg2_id":"663","normalized":[]},{"id":"679","type":"CID","arg1_id":"666","arg2_id":"665","normalized":[]},{"id":"680","type":"CID","arg1_id":"666","arg2_id":"669","normalized":[]},{"id":"681","type":"CID","arg1_id":"666","arg2_id":"672","normalized":[]},{"id":"682","type":"CID","arg1_id":"667","arg2_id":"663","normalized":[]},{"id":"683","type":"CID","arg1_id":"667","arg2_id":"665","normalized":[]},{"id":"684","type":"CID","arg1_id":"667","arg2_id":"669","normalized":[]},{"id":"685","type":"CID","arg1_id":"667","arg2_id":"672","normalized":[]},{"id":"686","type":"CID","arg1_id":"671","arg2_id":"663","normalized":[]},{"id":"687","type":"CID","arg1_id":"671","arg2_id":"665","normalized":[]},{"id":"688","type":"CID","arg1_id":"671","arg2_id":"669","normalized":[]},{"id":"689","type":"CID","arg1_id":"671","arg2_id":"672","normalized":[]}]}
{"id":"690","document_id":"2951327","passages":[{"id":"691","type":"title","text":["Inhibition of sympathoadrenal activity by atrial natriuretic factor in dogs."],"offsets":[[0,76]]},{"id":"692","type":"abstract","text":["In six conscious, trained dogs, maintained on a normal sodium intake of 2 to 4 mEq\/kg\/day, sympathetic activity was assessed as the release rate of norepinephrine and epinephrine during 15-minute i.v. infusions of human alpha-atrial natriuretic factor. Mean arterial pressure (as a percentage of control +\/- SEM) during randomized infusions of 0.03, 0.1, 0.3, or 1.0 microgram\/kg\/min was 99 +\/- 1, 95 +\/- 1 (p less than 0.05), 93 +\/- 1 (p less than 0.01), or 79 +\/- 6% (p less than 0.001), respectively, but no tachycardia and no augmentation of the norepinephrine release rate (up to 0.3 microgram\/kg\/min) were observed, which is in contrast to comparable hypotension induced by hydralazine or nitroglycerin. The release rate of epinephrine (control, 6.7 +\/- 0.6 ng\/kg\/min) declined immediately during infusions of atrial natriuretic factor to a minimum of 49 +\/- 5% of control (p less than 0.001) during 0.1 microgram\/kg\/min and to 63 +\/- 5% (0.1 greater than p greater than 0.05) or 95 +\/- 13% (not significant) during 0.3 or 1.0 microgram\/kg\/min. Steady state arterial plasma concentrations of atrial natriuretic factor were 39 +\/- 10 pg\/ml (n = 6) during infusions of saline and 284 +\/- 24 pg\/ml (n = 6) and 1520 +\/- 300 pg\/ml (n = 9) during 0.03 and 0.1 microgram\/kg\/min infusions of the factor.(ABSTRACT TRUNCATED AT 250 WORDS)"],"offsets":[[77,1411]]}],"entities":[{"id":"693","type":"Chemical","text":["sodium"],"offsets":[[132,138]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"694","type":"Chemical","text":["norepinephrine"],"offsets":[[225,239]],"normalized":[{"db_name":"MESH","db_id":"D009638"}]},{"id":"695","type":"Chemical","text":["epinephrine"],"offsets":[[244,255]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"696","type":"Disease","text":["tachycardia"],"offsets":[[588,599]],"normalized":[{"db_name":"MESH","db_id":"D013610"}]},{"id":"697","type":"Chemical","text":["norepinephrine"],"offsets":[[627,641]],"normalized":[{"db_name":"MESH","db_id":"D009638"}]},{"id":"698","type":"Disease","text":["hypotension"],"offsets":[[734,745]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"699","type":"Chemical","text":["hydralazine"],"offsets":[[757,768]],"normalized":[{"db_name":"MESH","db_id":"D006830"}]},{"id":"700","type":"Chemical","text":["nitroglycerin"],"offsets":[[772,785]],"normalized":[{"db_name":"MESH","db_id":"D005996"}]},{"id":"701","type":"Chemical","text":["epinephrine"],"offsets":[[807,818]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]}],"events":[],"coreferences":[],"relations":[{"id":"702","type":"CID","arg1_id":"700","arg2_id":"698","normalized":[]},{"id":"703","type":"CID","arg1_id":"699","arg2_id":"698","normalized":[]}]}
{"id":"704","document_id":"3192036","passages":[{"id":"705","type":"title","text":["Death from chemotherapy in gestational trophoblastic disease."],"offsets":[[0,61]]},{"id":"706","type":"abstract","text":["Multiple cytotoxic drug administration is the generally accepted treatment of patients with a high-risk stage of choriocarcinoma. Based on this principle a 27-year old woman, classified as being in the high-risk group (Goldstein and Berkowitz score: 11), was treated with multiple cytotoxic drugs. The multiple drug schema consisted of: Etoposide 16.213, Methotrexate, Cyclophosphamide, Actomycin-D, and Cisplatin. On the first day of the schedule, moderate high doses of Methotrexate, Etoposide and Cyclophosphamide were administered. Within 8 hours after initiation of therapy the patient died with a clinical picture resembling massive pulmonary obstruction due to choriocarcinomic tissue plugs, probably originating from the uterus. Formation of these plugs was probably due to extensive tumor necrosis at the level of the walls of the major uterine veins, which resulted in an open exchange of tumor plugs to the vascular spaces; decrease in tumor tissue coherence secondary to chemotherapy may have further contributed to the formation of tumor emboli. In view of the close time association between the start of chemotherapy and the acute onset of massive embolism other explanations, such as spontaneous necrosis, must be considered less likely. Patients with large pelvic tumor loads are, according to existing classifications, at high risk to die and to develop drug resistance. Notwithstanding these facts our findings suggest that these patients might benefit from relatively mild initial treatment, especially true for patients not previously exposed to this drug. Close observation of the response status both clinically and with beta-hCG values may indicate whether and when more agressive combination chemotherapy should be started.(ABSTRACT TRUNCATED AT 250 WORDS)"],"offsets":[[62,1842]]}],"entities":[{"id":"707","type":"Disease","text":["Death"],"offsets":[[0,5]],"normalized":[{"db_name":"MESH","db_id":"D003643"}]},{"id":"708","type":"Disease","text":["gestational trophoblastic disease"],"offsets":[[27,60]],"normalized":[{"db_name":"MESH","db_id":"D031901"}]},{"id":"709","type":"Disease","text":["choriocarcinoma"],"offsets":[[175,190]],"normalized":[{"db_name":"MESH","db_id":"D002822"}]},{"id":"710","type":"Chemical","text":["Etoposide"],"offsets":[[399,408]],"normalized":[{"db_name":"MESH","db_id":"D005047"}]},{"id":"711","type":"Chemical","text":["Methotrexate"],"offsets":[[417,429]],"normalized":[{"db_name":"MESH","db_id":"D008727"}]},{"id":"712","type":"Chemical","text":["Cyclophosphamide"],"offsets":[[431,447]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"713","type":"Chemical","text":["Actomycin-D"],"offsets":[[449,460]],"normalized":[{"db_name":"MESH","db_id":"D003609"}]},{"id":"714","type":"Chemical","text":["Cisplatin"],"offsets":[[466,475]],"normalized":[{"db_name":"MESH","db_id":"D002945"}]},{"id":"715","type":"Chemical","text":["Methotrexate"],"offsets":[[534,546]],"normalized":[{"db_name":"MESH","db_id":"D008727"}]},{"id":"716","type":"Chemical","text":["Etoposide"],"offsets":[[548,557]],"normalized":[{"db_name":"MESH","db_id":"D005047"}]},{"id":"717","type":"Chemical","text":["Cyclophosphamide"],"offsets":[[562,578]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"718","type":"Disease","text":["pulmonary obstruction"],"offsets":[[701,722]],"normalized":[{"db_name":"MESH","db_id":"D011655"}]},{"id":"719","type":"Disease","text":["tumor"],"offsets":[[854,859]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"720","type":"Disease","text":["necrosis"],"offsets":[[860,868]],"normalized":[{"db_name":"MESH","db_id":"D009336"}]},{"id":"721","type":"Disease","text":["tumor"],"offsets":[[961,966]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"722","type":"Disease","text":["tumor"],"offsets":[[1009,1014]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"723","type":"Disease","text":["tumor"],"offsets":[[1107,1112]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"724","type":"Disease","text":["embolism"],"offsets":[[1224,1232]],"normalized":[{"db_name":"MESH","db_id":"D004617"}]},{"id":"725","type":"Disease","text":["necrosis"],"offsets":[[1273,1281]],"normalized":[{"db_name":"MESH","db_id":"D009336"}]},{"id":"726","type":"Disease","text":["pelvic tumor"],"offsets":[[1335,1347]],"normalized":[{"db_name":"MESH","db_id":"D010386"}]}],"events":[],"coreferences":[],"relations":[{"id":"727","type":"CID","arg1_id":"710","arg2_id":"718","normalized":[]},{"id":"728","type":"CID","arg1_id":"716","arg2_id":"718","normalized":[]},{"id":"729","type":"CID","arg1_id":"711","arg2_id":"718","normalized":[]},{"id":"730","type":"CID","arg1_id":"715","arg2_id":"718","normalized":[]},{"id":"731","type":"CID","arg1_id":"712","arg2_id":"718","normalized":[]},{"id":"732","type":"CID","arg1_id":"717","arg2_id":"718","normalized":[]}]}
{"id":"733","document_id":"3409645","passages":[{"id":"734","type":"title","text":["Sexual dysfunction among patients with arthritis."],"offsets":[[0,49]]},{"id":"735","type":"abstract","text":["The relationship of arthritis and sexual dysfunction was investigated among 169 patients with rheumatoid arthritis, osteoarthritis and spondyloarthropathy, 130 of whom were pair-matched to controls. Assessments of marital happiness and depressed mood were also made using the CES-D and the Azrin Marital Happiness Scale (AMHS). Sexual dysfunctions were found to be common among patients and controls, the majority in both groups reporting one or more dysfunctions. Impotence was more common among male patients than controls and was found to be associated with co-morbidity and the taking of methotrexate. Depressed mood was more common among patients and was associated with certain sexual difficulties, but not with impotence. Marital unhappiness, as indicated by AMHS scores, was not associated with arthritis but was associated with sexual dysfunction, sexual dissatisfaction and being female."],"offsets":[[50,947]]}],"entities":[{"id":"736","type":"Disease","text":["Sexual dysfunction"],"offsets":[[0,18]],"normalized":[{"db_name":"MESH","db_id":"D012735"}]},{"id":"737","type":"Disease","text":["arthritis"],"offsets":[[39,48]],"normalized":[{"db_name":"MESH","db_id":"D001168"}]},{"id":"738","type":"Disease","text":["arthritis"],"offsets":[[70,79]],"normalized":[{"db_name":"MESH","db_id":"D001168"}]},{"id":"739","type":"Disease","text":["sexual dysfunction"],"offsets":[[84,102]],"normalized":[{"db_name":"MESH","db_id":"D012735"}]},{"id":"740","type":"Disease","text":["rheumatoid arthritis"],"offsets":[[144,164]],"normalized":[{"db_name":"MESH","db_id":"D001172"}]},{"id":"741","type":"Disease","text":["osteoarthritis"],"offsets":[[166,180]],"normalized":[{"db_name":"MESH","db_id":"D010003"}]},{"id":"742","type":"Disease","text":["spondyloarthropathy"],"offsets":[[185,204]],"normalized":[{"db_name":"MESH","db_id":"D025242"}]},{"id":"743","type":"Disease","text":["depressed mood"],"offsets":[[286,300]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"744","type":"Disease","text":["Sexual dysfunctions"],"offsets":[[378,397]],"normalized":[{"db_name":"MESH","db_id":"D012735"}]},{"id":"745","type":"Disease","text":["Impotence"],"offsets":[[515,524]],"normalized":[{"db_name":"MESH","db_id":"D007172"}]},{"id":"746","type":"Chemical","text":["methotrexate"],"offsets":[[642,654]],"normalized":[{"db_name":"MESH","db_id":"D008727"}]},{"id":"747","type":"Disease","text":["Depressed mood"],"offsets":[[656,670]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"748","type":"Disease","text":["impotence"],"offsets":[[768,777]],"normalized":[{"db_name":"MESH","db_id":"D007172"}]},{"id":"749","type":"Disease","text":["arthritis"],"offsets":[[853,862]],"normalized":[{"db_name":"MESH","db_id":"D001168"}]},{"id":"750","type":"Disease","text":["sexual dysfunction"],"offsets":[[887,905]],"normalized":[{"db_name":"MESH","db_id":"D012735"}]}],"events":[],"coreferences":[],"relations":[{"id":"751","type":"CID","arg1_id":"746","arg2_id":"745","normalized":[]},{"id":"752","type":"CID","arg1_id":"746","arg2_id":"748","normalized":[]}]}
{"id":"753","document_id":"3412544","passages":[{"id":"754","type":"title","text":["Does paracetamol cause urothelial cancer or renal papillary necrosis?"],"offsets":[[0,69]]},{"id":"755","type":"abstract","text":["The risk of developing renal papillary necrosis or cancer of the renal pelvis, ureter or bladder associated with consumption of either phenacetin or paracetamol was calculated from data acquired by questionnaire from 381 cases and 808 controls. The risk of renal papillary necrosis was increased nearly 20-fold by consumption of phenacetin, which also increased the risk for cancer of the renal pelvis and bladder but not for ureteric cancer. By contrast, we were unable to substantiate an increased risk from paracetamol consumption for renal papillary necrosis or any of these cancers although there was a suggestion of an association with cancer of the ureter."],"offsets":[[70,733]]}],"entities":[{"id":"756","type":"Chemical","text":["paracetamol"],"offsets":[[5,16]],"normalized":[{"db_name":"MESH","db_id":"D000082"}]},{"id":"757","type":"Disease","text":["urothelial cancer"],"offsets":[[23,40]],"normalized":[{"db_name":"MESH","db_id":"D014523"}]},{"id":"758","type":"Disease","text":["renal papillary necrosis"],"offsets":[[44,68]],"normalized":[{"db_name":"MESH","db_id":"D007681"}]},{"id":"759","type":"Disease","text":["renal papillary necrosis"],"offsets":[[93,117]],"normalized":[{"db_name":"MESH","db_id":"D007681"}]},{"id":"760","type":"Disease","text":["cancer of the renal pelvis, ureter or bladder"],"offsets":[[121,166]],"normalized":[{"db_name":"MESH","db_id":"D007680"},{"db_name":"MESH","db_id":"D014516"},{"db_name":"MESH","db_id":"D001749"}]},{"id":"761","type":"Disease","text":["cancer of the renal pelvis"],"offsets":[[121,147]],"normalized":[{"db_name":"MESH","db_id":"D007680"}]},{"id":"762","type":"Disease","text":["cancer of the","ureter"],"offsets":[[121,134],[149,155]],"normalized":[{"db_name":"MESH","db_id":"D014516"}]},{"id":"763","type":"Disease","text":["cancer of the","bladder"],"offsets":[[121,134],[159,166]],"normalized":[{"db_name":"MESH","db_id":"D001749"}]},{"id":"764","type":"Chemical","text":["phenacetin"],"offsets":[[205,215]],"normalized":[{"db_name":"MESH","db_id":"D010615"}]},{"id":"765","type":"Chemical","text":["paracetamol"],"offsets":[[219,230]],"normalized":[{"db_name":"MESH","db_id":"D000082"}]},{"id":"766","type":"Disease","text":["renal papillary necrosis"],"offsets":[[327,351]],"normalized":[{"db_name":"MESH","db_id":"D007681"}]},{"id":"767","type":"Chemical","text":["phenacetin"],"offsets":[[399,409]],"normalized":[{"db_name":"MESH","db_id":"D010615"}]},{"id":"768","type":"Disease","text":["cancer of the renal pelvis and bladder"],"offsets":[[445,483]],"normalized":[{"db_name":"MESH","db_id":"D007680"},{"db_name":"MESH","db_id":"D001749"}]},{"id":"769","type":"Disease","text":["cancer of the renal pelvis"],"offsets":[[445,471]],"normalized":[{"db_name":"MESH","db_id":"D007680"}]},{"id":"770","type":"Disease","text":["cancer of the","bladder"],"offsets":[[445,458],[476,483]],"normalized":[{"db_name":"MESH","db_id":"D001749"}]},{"id":"771","type":"Disease","text":["ureteric cancer"],"offsets":[[496,511]],"normalized":[{"db_name":"MESH","db_id":"D014516"}]},{"id":"772","type":"Chemical","text":["paracetamol"],"offsets":[[580,591]],"normalized":[{"db_name":"MESH","db_id":"D000082"}]},{"id":"773","type":"Disease","text":["renal papillary necrosis"],"offsets":[[608,632]],"normalized":[{"db_name":"MESH","db_id":"D007681"}]},{"id":"774","type":"Disease","text":["cancers"],"offsets":[[649,656]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"775","type":"Disease","text":["cancer of the ureter"],"offsets":[[712,732]],"normalized":[{"db_name":"MESH","db_id":"D014516"}]}],"events":[],"coreferences":[],"relations":[{"id":"776","type":"CID","arg1_id":"764","arg2_id":"758","normalized":[]},{"id":"777","type":"CID","arg1_id":"764","arg2_id":"759","normalized":[]},{"id":"778","type":"CID","arg1_id":"764","arg2_id":"766","normalized":[]},{"id":"779","type":"CID","arg1_id":"764","arg2_id":"773","normalized":[]},{"id":"780","type":"CID","arg1_id":"767","arg2_id":"758","normalized":[]},{"id":"781","type":"CID","arg1_id":"767","arg2_id":"759","normalized":[]},{"id":"782","type":"CID","arg1_id":"767","arg2_id":"766","normalized":[]},{"id":"783","type":"CID","arg1_id":"767","arg2_id":"773","normalized":[]},{"id":"784","type":"CID","arg1_id":"764","arg2_id":"760","normalized":[]},{"id":"785","type":"CID","arg1_id":"764","arg2_id":"763","normalized":[]},{"id":"786","type":"CID","arg1_id":"764","arg2_id":"768","normalized":[]},{"id":"787","type":"CID","arg1_id":"764","arg2_id":"770","normalized":[]},{"id":"788","type":"CID","arg1_id":"767","arg2_id":"760","normalized":[]},{"id":"789","type":"CID","arg1_id":"767","arg2_id":"763","normalized":[]},{"id":"790","type":"CID","arg1_id":"767","arg2_id":"768","normalized":[]},{"id":"791","type":"CID","arg1_id":"767","arg2_id":"770","normalized":[]},{"id":"792","type":"CID","arg1_id":"764","arg2_id":"760","normalized":[]},{"id":"793","type":"CID","arg1_id":"764","arg2_id":"761","normalized":[]},{"id":"794","type":"CID","arg1_id":"764","arg2_id":"768","normalized":[]},{"id":"795","type":"CID","arg1_id":"764","arg2_id":"769","normalized":[]},{"id":"796","type":"CID","arg1_id":"767","arg2_id":"760","normalized":[]},{"id":"797","type":"CID","arg1_id":"767","arg2_id":"761","normalized":[]},{"id":"798","type":"CID","arg1_id":"767","arg2_id":"768","normalized":[]},{"id":"799","type":"CID","arg1_id":"767","arg2_id":"769","normalized":[]}]}
{"id":"800","document_id":"3425586","passages":[{"id":"801","type":"title","text":["Dapsone-associated Heinz body hemolytic anemia in a Cambodian woman with hemoglobin E trait."],"offsets":[[0,92]]},{"id":"802","type":"abstract","text":["A Cambodian woman with hemoglobin E trait (AE) and leprosy developed a Heinz body hemolytic anemia while taking a dose of dapsone (50 mg\/day) not usually associated with clinical hemolysis. Her red blood cells (RBCs) had increased incubated Heinz body formation, decreased reduced glutathione (GSH), and decreased GSH stability. The pentose phosphate shunt activity of the dapsone-exposed AE RBCs was increased compared to normal RBCs. Although the AE RBCs from an individual not taking dapsone had increased incubated Heinz body formation, the GSH content and GSH stability were normal. The pentose phosphate shunt activity of the non-dapsone-exposed AE RBCs was decreased compared to normal RBCs. Thus, AE RBCs appear to have an increased sensitivity to oxidant stress both in vitro and in vivo, since dapsone does not cause hemolytic anemia at this dose in hematologically normal individuals. Given the influx of Southeast Asians into the United States, oxidant medications should be used with caution, especially if an infection is present, in individuals of ethnic backgrounds that have an increased prevalence of hemoglobin E."],"offsets":[[93,1225]]}],"entities":[{"id":"803","type":"Chemical","text":["Dapsone"],"offsets":[[0,7]],"normalized":[{"db_name":"MESH","db_id":"D003622"}]},{"id":"804","type":"Disease","text":["hemolytic anemia"],"offsets":[[30,46]],"normalized":[{"db_name":"MESH","db_id":"D000743"}]},{"id":"805","type":"Disease","text":["leprosy"],"offsets":[[144,151]],"normalized":[{"db_name":"MESH","db_id":"D007918"}]},{"id":"806","type":"Disease","text":["hemolytic anemia"],"offsets":[[175,191]],"normalized":[{"db_name":"MESH","db_id":"D000743"}]},{"id":"807","type":"Chemical","text":["dapsone"],"offsets":[[215,222]],"normalized":[{"db_name":"MESH","db_id":"D003622"}]},{"id":"808","type":"Disease","text":["hemolysis"],"offsets":[[272,281]],"normalized":[{"db_name":"MESH","db_id":"D006461"}]},{"id":"809","type":"Chemical","text":["glutathione"],"offsets":[[374,385]],"normalized":[{"db_name":"MESH","db_id":"D005978"}]},{"id":"810","type":"Chemical","text":["GSH"],"offsets":[[387,390]],"normalized":[{"db_name":"MESH","db_id":"D005978"}]},{"id":"811","type":"Chemical","text":["GSH"],"offsets":[[407,410]],"normalized":[{"db_name":"MESH","db_id":"D005978"}]},{"id":"812","type":"Chemical","text":["pentose phosphate"],"offsets":[[426,443]],"normalized":[{"db_name":"MESH","db_id":"D010428"}]},{"id":"813","type":"Chemical","text":["dapsone"],"offsets":[[466,473]],"normalized":[{"db_name":"MESH","db_id":"D003622"}]},{"id":"814","type":"Chemical","text":["dapsone"],"offsets":[[580,587]],"normalized":[{"db_name":"MESH","db_id":"D003622"}]},{"id":"815","type":"Chemical","text":["GSH"],"offsets":[[638,641]],"normalized":[{"db_name":"MESH","db_id":"D005978"}]},{"id":"816","type":"Chemical","text":["GSH"],"offsets":[[654,657]],"normalized":[{"db_name":"MESH","db_id":"D005978"}]},{"id":"817","type":"Chemical","text":["pentose phosphate"],"offsets":[[685,702]],"normalized":[{"db_name":"MESH","db_id":"D010428"}]},{"id":"818","type":"Chemical","text":["dapsone"],"offsets":[[729,736]],"normalized":[{"db_name":"MESH","db_id":"D003622"}]},{"id":"819","type":"Chemical","text":["dapsone"],"offsets":[[897,904]],"normalized":[{"db_name":"MESH","db_id":"D003622"}]},{"id":"820","type":"Disease","text":["hemolytic anemia"],"offsets":[[920,936]],"normalized":[{"db_name":"MESH","db_id":"D000743"}]},{"id":"821","type":"Disease","text":["infection"],"offsets":[[1116,1125]],"normalized":[{"db_name":"MESH","db_id":"D007239"}]}],"events":[],"coreferences":[],"relations":[{"id":"822","type":"CID","arg1_id":"803","arg2_id":"804","normalized":[]},{"id":"823","type":"CID","arg1_id":"803","arg2_id":"806","normalized":[]},{"id":"824","type":"CID","arg1_id":"803","arg2_id":"820","normalized":[]},{"id":"825","type":"CID","arg1_id":"807","arg2_id":"804","normalized":[]},{"id":"826","type":"CID","arg1_id":"807","arg2_id":"806","normalized":[]},{"id":"827","type":"CID","arg1_id":"807","arg2_id":"820","normalized":[]},{"id":"828","type":"CID","arg1_id":"813","arg2_id":"804","normalized":[]},{"id":"829","type":"CID","arg1_id":"813","arg2_id":"806","normalized":[]},{"id":"830","type":"CID","arg1_id":"813","arg2_id":"820","normalized":[]},{"id":"831","type":"CID","arg1_id":"814","arg2_id":"804","normalized":[]},{"id":"832","type":"CID","arg1_id":"814","arg2_id":"806","normalized":[]},{"id":"833","type":"CID","arg1_id":"814","arg2_id":"820","normalized":[]},{"id":"834","type":"CID","arg1_id":"818","arg2_id":"804","normalized":[]},{"id":"835","type":"CID","arg1_id":"818","arg2_id":"806","normalized":[]},{"id":"836","type":"CID","arg1_id":"818","arg2_id":"820","normalized":[]},{"id":"837","type":"CID","arg1_id":"819","arg2_id":"804","normalized":[]},{"id":"838","type":"CID","arg1_id":"819","arg2_id":"806","normalized":[]},{"id":"839","type":"CID","arg1_id":"819","arg2_id":"820","normalized":[]}]}
{"id":"840","document_id":"3437726","passages":[{"id":"841","type":"title","text":["Severe complications of antianginal drug therapy in a patient identified as a poor metabolizer of metoprolol, propafenone, diltiazem, and sparteine."],"offsets":[[0,148]]},{"id":"842","type":"abstract","text":["A 47-year-old patient suffering from coronary artery disease was admitted to the CCU in shock with III. AV block, severe hypotension, and impairment of ventricular function. One week prior to admission a therapy with standard doses of metoprolol (100 mg t.i.d. and then 100 mg b.i.d.) had been initiated. Two days before admission diltiazem (60 mg b.i.d.) was prescribed in addition. Analyses of a blood sample revealed unusually high plasma concentrations of metoprolol (greater than 3000 ng\/ml) and diltiazem (526 ng\/ml). The patient recovered within 1 week following discontinuation of antianginal therapy. Three months later the patient was exposed to a single dose of metoprolol, diltiazem, propafenone (since he had received this drug in the past), and sparteine (as a probe for the debrisoquine\/sparteine type polymorphism of oxidative drug metabolism). It was found that he was a poor metabolizer of all four drugs, indicating that their metabolism is under the same genetic control. Therefore, patients belonging to the poor-metabolizer phenotype of sparteine\/debrisoquine polymorphism in drug metabolism, which constitutes 6.4% of the German population, may experience adverse drug reactions when treated with standard doses of one of these drugs alone. Moreover, the coadministration of these frequently used drugs is expected to be especially harmful in this subgroup of patients."],"offsets":[[149,1541]]}],"entities":[{"id":"843","type":"Chemical","text":["metoprolol"],"offsets":[[98,108]],"normalized":[{"db_name":"MESH","db_id":"D008790"}]},{"id":"844","type":"Chemical","text":["propafenone"],"offsets":[[110,121]],"normalized":[{"db_name":"MESH","db_id":"D011405"}]},{"id":"845","type":"Chemical","text":["diltiazem"],"offsets":[[123,132]],"normalized":[{"db_name":"MESH","db_id":"D004110"}]},{"id":"846","type":"Chemical","text":["sparteine"],"offsets":[[138,147]],"normalized":[{"db_name":"MESH","db_id":"D013034"}]},{"id":"847","type":"Disease","text":["coronary artery disease"],"offsets":[[186,209]],"normalized":[{"db_name":"MESH","db_id":"D003324"}]},{"id":"848","type":"Disease","text":["shock"],"offsets":[[237,242]],"normalized":[{"db_name":"MESH","db_id":"D012769"}]},{"id":"849","type":"Disease","text":["AV block"],"offsets":[[253,261]],"normalized":[{"db_name":"MESH","db_id":"D054537"}]},{"id":"850","type":"Disease","text":["hypotension"],"offsets":[[270,281]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"851","type":"Disease","text":["impairment of ventricular function"],"offsets":[[287,321]],"normalized":[{"db_name":"MESH","db_id":"D018754"}]},{"id":"852","type":"Chemical","text":["metoprolol"],"offsets":[[384,394]],"normalized":[{"db_name":"MESH","db_id":"D008790"}]},{"id":"853","type":"Chemical","text":["diltiazem"],"offsets":[[480,489]],"normalized":[{"db_name":"MESH","db_id":"D004110"}]},{"id":"854","type":"Chemical","text":["metoprolol"],"offsets":[[609,619]],"normalized":[{"db_name":"MESH","db_id":"D008790"}]},{"id":"855","type":"Chemical","text":["diltiazem"],"offsets":[[650,659]],"normalized":[{"db_name":"MESH","db_id":"D004110"}]},{"id":"856","type":"Chemical","text":["metoprolol"],"offsets":[[822,832]],"normalized":[{"db_name":"MESH","db_id":"D008790"}]},{"id":"857","type":"Chemical","text":["diltiazem"],"offsets":[[834,843]],"normalized":[{"db_name":"MESH","db_id":"D004110"}]},{"id":"858","type":"Chemical","text":["propafenone"],"offsets":[[845,856]],"normalized":[{"db_name":"MESH","db_id":"D011405"}]},{"id":"859","type":"Chemical","text":["sparteine"],"offsets":[[908,917]],"normalized":[{"db_name":"MESH","db_id":"D013034"}]},{"id":"860","type":"Chemical","text":["debrisoquine"],"offsets":[[938,950]],"normalized":[{"db_name":"MESH","db_id":"D003647"}]},{"id":"861","type":"Chemical","text":["sparteine"],"offsets":[[951,960]],"normalized":[{"db_name":"MESH","db_id":"D013034"}]},{"id":"862","type":"Chemical","text":["sparteine"],"offsets":[[1208,1217]],"normalized":[{"db_name":"MESH","db_id":"D013034"}]},{"id":"863","type":"Chemical","text":["debrisoquine"],"offsets":[[1218,1230]],"normalized":[{"db_name":"MESH","db_id":"D003647"}]},{"id":"864","type":"Disease","text":["adverse drug reactions"],"offsets":[[1328,1350]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]}],"events":[],"coreferences":[],"relations":[{"id":"865","type":"CID","arg1_id":"845","arg2_id":"850","normalized":[]},{"id":"866","type":"CID","arg1_id":"853","arg2_id":"850","normalized":[]},{"id":"867","type":"CID","arg1_id":"855","arg2_id":"850","normalized":[]},{"id":"868","type":"CID","arg1_id":"857","arg2_id":"850","normalized":[]},{"id":"869","type":"CID","arg1_id":"845","arg2_id":"851","normalized":[]},{"id":"870","type":"CID","arg1_id":"853","arg2_id":"851","normalized":[]},{"id":"871","type":"CID","arg1_id":"855","arg2_id":"851","normalized":[]},{"id":"872","type":"CID","arg1_id":"857","arg2_id":"851","normalized":[]},{"id":"873","type":"CID","arg1_id":"843","arg2_id":"851","normalized":[]},{"id":"874","type":"CID","arg1_id":"852","arg2_id":"851","normalized":[]},{"id":"875","type":"CID","arg1_id":"854","arg2_id":"851","normalized":[]},{"id":"876","type":"CID","arg1_id":"856","arg2_id":"851","normalized":[]},{"id":"877","type":"CID","arg1_id":"843","arg2_id":"850","normalized":[]},{"id":"878","type":"CID","arg1_id":"852","arg2_id":"850","normalized":[]},{"id":"879","type":"CID","arg1_id":"854","arg2_id":"850","normalized":[]},{"id":"880","type":"CID","arg1_id":"856","arg2_id":"850","normalized":[]},{"id":"881","type":"CID","arg1_id":"845","arg2_id":"849","normalized":[]},{"id":"882","type":"CID","arg1_id":"853","arg2_id":"849","normalized":[]},{"id":"883","type":"CID","arg1_id":"855","arg2_id":"849","normalized":[]},{"id":"884","type":"CID","arg1_id":"857","arg2_id":"849","normalized":[]},{"id":"885","type":"CID","arg1_id":"843","arg2_id":"849","normalized":[]},{"id":"886","type":"CID","arg1_id":"852","arg2_id":"849","normalized":[]},{"id":"887","type":"CID","arg1_id":"854","arg2_id":"849","normalized":[]},{"id":"888","type":"CID","arg1_id":"856","arg2_id":"849","normalized":[]}]}
{"id":"889","document_id":"3693336","passages":[{"id":"890","type":"title","text":["Triazolam-induced brief episodes of secondary mania in a depressed patient."],"offsets":[[0,75]]},{"id":"891","type":"abstract","text":["Large doses of triazolam repeatedly induced brief episodes of mania in a depressed elderly woman. Features of organic mental disorder (delirium) were not present. Manic excitement was coincident with the duration of action of triazolam. The possible contribution of the triazolo group to changes in affective status is discussed."],"offsets":[[76,405]]}],"entities":[{"id":"892","type":"Chemical","text":["Triazolam"],"offsets":[[0,9]],"normalized":[{"db_name":"MESH","db_id":"D014229"}]},{"id":"893","type":"Disease","text":["mania"],"offsets":[[46,51]],"normalized":[{"db_name":"MESH","db_id":"D001714"}]},{"id":"894","type":"Disease","text":["depressed"],"offsets":[[57,66]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"895","type":"Chemical","text":["triazolam"],"offsets":[[91,100]],"normalized":[{"db_name":"MESH","db_id":"D014229"}]},{"id":"896","type":"Disease","text":["mania"],"offsets":[[138,143]],"normalized":[{"db_name":"MESH","db_id":"D001714"}]},{"id":"897","type":"Disease","text":["depressed"],"offsets":[[149,158]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"898","type":"Disease","text":["organic mental disorder"],"offsets":[[186,209]],"normalized":[{"db_name":"MESH","db_id":"D019965"}]},{"id":"899","type":"Disease","text":["delirium"],"offsets":[[211,219]],"normalized":[{"db_name":"MESH","db_id":"D003693"}]},{"id":"900","type":"Disease","text":["Manic"],"offsets":[[239,244]],"normalized":[{"db_name":"MESH","db_id":"D001714"}]},{"id":"901","type":"Chemical","text":["triazolam"],"offsets":[[302,311]],"normalized":[{"db_name":"MESH","db_id":"D014229"}]},{"id":"902","type":"Chemical","text":["triazolo"],"offsets":[[346,354]],"normalized":[{"db_name":"MESH","db_id":"D014229"}]}],"events":[],"coreferences":[],"relations":[{"id":"903","type":"CID","arg1_id":"892","arg2_id":"893","normalized":[]},{"id":"904","type":"CID","arg1_id":"892","arg2_id":"896","normalized":[]},{"id":"905","type":"CID","arg1_id":"892","arg2_id":"900","normalized":[]},{"id":"906","type":"CID","arg1_id":"895","arg2_id":"893","normalized":[]},{"id":"907","type":"CID","arg1_id":"895","arg2_id":"896","normalized":[]},{"id":"908","type":"CID","arg1_id":"895","arg2_id":"900","normalized":[]},{"id":"909","type":"CID","arg1_id":"901","arg2_id":"893","normalized":[]},{"id":"910","type":"CID","arg1_id":"901","arg2_id":"896","normalized":[]},{"id":"911","type":"CID","arg1_id":"901","arg2_id":"900","normalized":[]},{"id":"912","type":"CID","arg1_id":"902","arg2_id":"893","normalized":[]},{"id":"913","type":"CID","arg1_id":"902","arg2_id":"896","normalized":[]},{"id":"914","type":"CID","arg1_id":"902","arg2_id":"900","normalized":[]}]}
{"id":"915","document_id":"3780846","passages":[{"id":"916","type":"title","text":["On the mechanisms of the development of tolerance to the muscular rigidity produced by morphine in rats."],"offsets":[[0,104]]},{"id":"917","type":"abstract","text":["The development of tolerance to the muscular rigidity produced by morphine was studied in rats. Saline-pretreated controls given a test dose of morphine (20 mg\/kg i.p.) showed a pronounced rigidity recorded as tonic activity in the electromyogram. Rats treated for 11 days with morphine and withdrawn for 36-40 h showed differences in the development of tolerance: about half of the animals showed a rigidity after the test dose of morphine that was not significantly less than in the controls and were akinetic (A group). The other rats showed a strong decrease in the rigidity and the occurrence of stereotyped (S) licking and\/or gnawing in presence of akinetic or hyperkinetic (K) behaviour (AS\/KS group), suggesting signs of dopaminergic activation. The rigidity was considerably decreased in both groups after 20 days' treatment. In a further series of experiments, haloperidol (0.2 mg\/kg i.p.) was used in order to block the dopaminergic activation and to estimate the real degree of the tolerance to the rigidity without any dopaminergic interference. Haloperidol enhanced the rigidity in the A group. However, the level in the AS\/KS group remained considerably lower than in the A group. The results suggest that rigidity, which is assumed to be due to an action of morphine in the striatum, can be antagonized by another process leading to dopaminergic activation in the striatum. Nevertheless, there occurs some real tolerance to this effect. The rapid alternations of rigidity and the signs of dopaminergic activation observed in the animals of the AS\/KS group might be due to rapid shifts in the predominance of various DA-innervated structures."],"offsets":[[105,1762]]}],"entities":[{"id":"918","type":"Disease","text":["muscular rigidity"],"offsets":[[57,74]],"normalized":[{"db_name":"MESH","db_id":"D009127"}]},{"id":"919","type":"Chemical","text":["morphine"],"offsets":[[87,95]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"920","type":"Disease","text":["muscular 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{"id":"1037","document_id":"3800626","passages":[{"id":"1038","type":"title","text":["Compression neuropathy of the radial nerve due to pentazocine-induced fibrous myopathy."],"offsets":[[0,87]]},{"id":"1039","type":"abstract","text":["Fibrous myopathy is a common, well-known side effect of repeated pentazocine injection. However, compression neuropathy due to fibrotic muscle affected by pentazocine-induced myopathy has not previously been reported. In a 37-year-old woman with documented pentazocine-induced fibrous myopathy of triceps and deltoid muscles bilaterally and a three-week history of right wrist drop, electrodiagnostic examination showed a severe but partial lesion of the right radial nerve distal to the branches to the triceps, in addition to the fibrous myopathy. Surgery revealed the right radial nerve to be severely compressed by the densely fibrotic lateral head of the triceps. Decompression and neurolysis were performed with good subsequent recovery of function."],"offsets":[[88,843]]}],"entities":[{"id":"1040","type":"Disease","text":["Compression neuropathy of the radial nerve"],"offsets":[[0,42]],"normalized":[{"db_name":"MESH","db_id":"D009408"},{"db_name":"MESH","db_id":"D020425"}]},{"id":"1041","type":"Disease","text":["Compression neuropathy"],"offsets":[[0,22]],"normalized":[{"db_name":"MESH","db_id":"D009408"}]},{"id":"1042","type":"Disease","text":["neuropathy of the radial nerve"],"offsets":[[12,42]],"normalized":[{"db_name":"MESH","db_id":"D020425"}]},{"id":"1043","type":"Chemical","text":["pentazocine"],"offsets":[[50,61]],"normalized":[{"db_name":"MESH","db_id":"D010423"}]},{"id":"1044","type":"Disease","text":["fibrous myopathy"],"offsets":[[70,86]],"normalized":[{"db_name":"MESH","db_id":"D005355"},{"db_name":"MESH","db_id":"D009135"}]},{"id":"1045","type":"Disease","text":["Fibrous 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{"id":"1109","document_id":"3827439","passages":[{"id":"1110","type":"title","text":["Recurrent reversible acute renal failure from amphotericin."],"offsets":[[0,59]]},{"id":"1111","type":"abstract","text":["A patient with cryptogenic cirrhosis and disseminated sporotrichosis developed acute renal failure immediately following the administration of amphotericin B on four separate occasions. The abruptness of the renal failure and its reversibility within days suggests that there was a functional component to the renal dysfunction. We propose that amphotericin, in the setting of reduced effective arterial volume, may activate tubuloglomerular feedback, thereby contributing to acute renal failure."],"offsets":[[60,556]]}],"entities":[{"id":"1112","type":"Disease","text":["acute renal failure"],"offsets":[[21,40]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"1113","type":"Chemical","text":["amphotericin"],"offsets":[[46,58]],"normalized":[{"db_name":"MESH","db_id":"D000666"}]},{"id":"1114","type":"Disease","text":["cirrhosis"],"offsets":[[87,96]],"normalized":[{"db_name":"MESH","db_id":"D005355"}]},{"id":"1115","type":"Disease","text":["sporotrichosis"],"offsets":[[114,128]],"normalized":[{"db_name":"MESH","db_id":"D013174"}]},{"id":"1116","type":"Disease","text":["acute renal failure"],"offsets":[[139,158]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"1117","type":"Chemical","text":["amphotericin B"],"offsets":[[203,217]],"normalized":[{"db_name":"MESH","db_id":"D000666"}]},{"id":"1118","type":"Disease","text":["renal failure"],"offsets":[[268,281]],"normalized":[{"db_name":"MESH","db_id":"D051437"}]},{"id":"1119","type":"Disease","text":["renal dysfunction"],"offsets":[[370,387]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"1120","type":"Chemical","text":["amphotericin"],"offsets":[[405,417]],"normalized":[{"db_name":"MESH","db_id":"D000666"}]},{"id":"1121","type":"Disease","text":["acute renal failure"],"offsets":[[536,555]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]}],"events":[],"coreferences":[],"relations":[{"id":"1122","type":"CID","arg1_id":"1113","arg2_id":"1112","normalized":[]},{"id":"1123","type":"CID","arg1_id":"1113","arg2_id":"1116","normalized":[]},{"id":"1124","type":"CID","arg1_id":"1113","arg2_id":"1121","normalized":[]},{"id":"1125","type":"CID","arg1_id":"1117","arg2_id":"1112","normalized":[]},{"id":"1126","type":"CID","arg1_id":"1117","arg2_id":"1116","normalized":[]},{"id":"1127","type":"CID","arg1_id":"1117","arg2_id":"1121","normalized":[]},{"id":"1128","type":"CID","arg1_id":"1120","arg2_id":"1112","normalized":[]},{"id":"1129","type":"CID","arg1_id":"1120","arg2_id":"1116","normalized":[]},{"id":"1130","type":"CID","arg1_id":"1120","arg2_id":"1121","normalized":[]}]}
{"id":"1131","document_id":"3997294","passages":[{"id":"1132","type":"title","text":["Pneumonitis with pleural and pericardial effusion and neuropathy during amiodarone therapy."],"offsets":[[0,91]]},{"id":"1133","type":"abstract","text":["A patient with sinuatrial disease and implanted pacemaker was treated with amiodarone (maximum dose 1000 mg, maintenance dose 800 mg daily) for 10 months, for control of supraventricular tachyarrhythmias. He developed pneumonitis, pleural and pericardial effusions, and a predominantly proximal motor neuropathy. Immediate but gradual improvement followed withdrawal of amiodarone and treatment with prednisolone. Review of this and previously reported cases indicates the need for early diagnosis of amiodarone pneumonitis, immediate withdrawal of amiodarone, and prompt but continued steroid therapy to ensure full recovery."],"offsets":[[92,718]]}],"entities":[{"id":"1134","type":"Disease","text":["pleural and pericardial effusion"],"offsets":[[17,49]],"normalized":[{"db_name":"MESH","db_id":"D010996"},{"db_name":"MESH","db_id":"D010490"}]},{"id":"1135","type":"Disease","text":["pleural","effusion"],"offsets":[[17,24],[41,49]],"normalized":[{"db_name":"MESH","db_id":"D010996"}]},{"id":"1136","type":"Disease","text":["pericardial 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{"id":"1208","document_id":"4071154","passages":[{"id":"1209","type":"title","text":["Indomethacin-induced renal insufficiency: recurrence on rechallenge."],"offsets":[[0,68]]},{"id":"1210","type":"abstract","text":["We have reported a case of acute oliguric renal failure with hyperkalemia in a patient with cirrhosis, ascites, and cor pulmonale after indomethacin therapy. Prompt restoration of renal function followed drug withdrawal, while re-exposure to a single dose of indomethacin caused recurrence of acute reversible oliguria. Our case supports the hypothesis that endogenous renal prostaglandins play a role in the maintenance of renal blood flow when circulating plasma volume is diminished. Since nonsteroidal anti-inflammatory agents interfere with this compensatory mechanism and may cause acute renal failure, they should be used with caution in such patients."],"offsets":[[69,728]]}],"entities":[{"id":"1211","type":"Chemical","text":["Indomethacin"],"offsets":[[0,12]],"normalized":[{"db_name":"MESH","db_id":"D007213"}]},{"id":"1212","type":"Disease","text":["renal insufficiency"],"offsets":[[21,40]],"normalized":[{"db_name":"MESH","db_id":"D051437"}]},{"id":"1213","type":"Disease","text":["renal failure"],"offsets":[[111,124]],"normalized":[{"db_name":"MESH","db_id":"D051437"}]},{"id":"1214","type":"Disease","text":["hyperkalemia"],"offsets":[[130,142]],"normalized":[{"db_name":"MESH","db_id":"D006947"}]},{"id":"1215","type":"Disease","text":["cirrhosis"],"offsets":[[161,170]],"normalized":[{"db_name":"MESH","db_id":"D005355"}]},{"id":"1216","type":"Disease","text":["ascites"],"offsets":[[172,179]],"normalized":[{"db_name":"MESH","db_id":"D001201"}]},{"id":"1217","type":"Disease","text":["cor pulmonale"],"offsets":[[185,198]],"normalized":[{"db_name":"MESH","db_id":"D011660"}]},{"id":"1218","type":"Chemical","text":["indomethacin"],"offsets":[[205,217]],"normalized":[{"db_name":"MESH","db_id":"D007213"}]},{"id":"1219","type":"Chemical","text":["indomethacin"],"offsets":[[328,340]],"normalized":[{"db_name":"MESH","db_id":"D007213"}]},{"id":"1220","type":"Disease","text":["oliguria"],"offsets":[[379,387]],"normalized":[{"db_name":"MESH","db_id":"D009846"}]},{"id":"1221","type":"Chemical","text":["prostaglandins"],"offsets":[[444,458]],"normalized":[{"db_name":"MESH","db_id":"D011453"}]},{"id":"1222","type":"Disease","text":["acute renal failure"],"offsets":[[657,676]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]}],"events":[],"coreferences":[],"relations":[{"id":"1223","type":"CID","arg1_id":"1211","arg2_id":"1214","normalized":[]},{"id":"1224","type":"CID","arg1_id":"1218","arg2_id":"1214","normalized":[]},{"id":"1225","type":"CID","arg1_id":"1219","arg2_id":"1214","normalized":[]},{"id":"1226","type":"CID","arg1_id":"1211","arg2_id":"1220","normalized":[]},{"id":"1227","type":"CID","arg1_id":"1218","arg2_id":"1220","normalized":[]},{"id":"1228","type":"CID","arg1_id":"1219","arg2_id":"1220","normalized":[]},{"id":"1229","type":"CID","arg1_id":"1211","arg2_id":"1222","normalized":[]},{"id":"1230","type":"CID","arg1_id":"1218","arg2_id":"1222","normalized":[]},{"id":"1231","type":"CID","arg1_id":"1219","arg2_id":"1222","normalized":[]},{"id":"1232","type":"CID","arg1_id":"1211","arg2_id":"1215","normalized":[]},{"id":"1233","type":"CID","arg1_id":"1218","arg2_id":"1215","normalized":[]},{"id":"1234","type":"CID","arg1_id":"1219","arg2_id":"1215","normalized":[]},{"id":"1235","type":"CID","arg1_id":"1211","arg2_id":"1216","normalized":[]},{"id":"1236","type":"CID","arg1_id":"1218","arg2_id":"1216","normalized":[]},{"id":"1237","type":"CID","arg1_id":"1219","arg2_id":"1216","normalized":[]},{"id":"1238","type":"CID","arg1_id":"1211","arg2_id":"1217","normalized":[]},{"id":"1239","type":"CID","arg1_id":"1218","arg2_id":"1217","normalized":[]},{"id":"1240","type":"CID","arg1_id":"1219","arg2_id":"1217","normalized":[]}]}
{"id":"1241","document_id":"6103707","passages":[{"id":"1242","type":"title","text":["Comparison of the subjective effects and plasma concentrations following oral and i.m. administration of flunitrazepam in volunteers."],"offsets":[[0,133]]},{"id":"1243","type":"abstract","text":["Flunitrazepam 0.5, 1.0 or 2.0 mg was given by the oral or i.m. routes to groups of volunteers and its effects compared. Plasma concentrations of the drug were estimated by gas-liquid chromatography, in a smaller number of the subjects. The most striking effect was sedation which increased with the dose, 2 mg producing deep sleep although the subjects could still be aroused. The effects of i.m. administration were apparent earlier and sometimes lasted longer than those following oral administration. Dizziness was less marked than sedation, but increased with the dose. There was pain on i.m. injection of flunitrazepam significantly more often than with isotonic saline. Plasma concentrations varied with dose and route and corresponded qualitatively with the subjective effects. The drug was still present in measurable quantities after 24 h even with the smallest dose."],"offsets":[[134,1010]]}],"entities":[{"id":"1244","type":"Chemical","text":["flunitrazepam"],"offsets":[[105,118]],"normalized":[{"db_name":"MESH","db_id":"D005445"}]},{"id":"1245","type":"Chemical","text":["Flunitrazepam"],"offsets":[[134,147]],"normalized":[{"db_name":"MESH","db_id":"D005445"}]},{"id":"1246","type":"Disease","text":["Dizziness"],"offsets":[[638,647]],"normalized":[{"db_name":"MESH","db_id":"D004244"}]},{"id":"1247","type":"Disease","text":["pain"],"offsets":[[718,722]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"1248","type":"Chemical","text":["flunitrazepam"],"offsets":[[744,757]],"normalized":[{"db_name":"MESH","db_id":"D005445"}]}],"events":[],"coreferences":[],"relations":[{"id":"1249","type":"CID","arg1_id":"1244","arg2_id":"1246","normalized":[]},{"id":"1250","type":"CID","arg1_id":"1245","arg2_id":"1246","normalized":[]},{"id":"1251","type":"CID","arg1_id":"1248","arg2_id":"1246","normalized":[]},{"id":"1252","type":"CID","arg1_id":"1244","arg2_id":"1247","normalized":[]},{"id":"1253","type":"CID","arg1_id":"1245","arg2_id":"1247","normalized":[]},{"id":"1254","type":"CID","arg1_id":"1248","arg2_id":"1247","normalized":[]}]}
{"id":"1255","document_id":"6229975","passages":[{"id":"1256","type":"title","text":["Changes in heart size during long-term timolol treatment after myocardial infarction."],"offsets":[[0,85]]},{"id":"1257","type":"abstract","text":["The effect of long-term timolol treatment on heart size after myocardial infarction was evaluated by X-ray in a double-blind study including 241 patients (placebo 126, timolol 115). The follow-up period was 12 months. The timolol-treated patients showed a small but significant increase in heart size from baseline in contrast to a decrease in the placebo group. These differences may be caused by timolol-induced bradycardia and a compensatory increase in end-diastolic volume. The timolol-related increase in heart size was observed only in patients with normal and borderline heart size. In patients with cardiomegaly, the increase in heart size was similar in both groups. After re-infarction, heart size increased in the placebo group and remained unchanged in the timolol group."],"offsets":[[86,870]]}],"entities":[{"id":"1258","type":"Chemical","text":["timolol"],"offsets":[[39,46]],"normalized":[{"db_name":"MESH","db_id":"D013999"}]},{"id":"1259","type":"Disease","text":["myocardial infarction"],"offsets":[[63,84]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"1260","type":"Chemical","text":["timolol"],"offsets":[[110,117]],"normalized":[{"db_name":"MESH","db_id":"D013999"}]},{"id":"1261","type":"Disease","text":["myocardial infarction"],"offsets":[[148,169]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"1262","type":"Chemical","text":["timolol"],"offsets":[[254,261]],"normalized":[{"db_name":"MESH","db_id":"D013999"}]},{"id":"1263","type":"Chemical","text":["timolol"],"offsets":[[308,315]],"normalized":[{"db_name":"MESH","db_id":"D013999"}]},{"id":"1264","type":"Chemical","text":["timolol"],"offsets":[[484,491]],"normalized":[{"db_name":"MESH","db_id":"D013999"}]},{"id":"1265","type":"Disease","text":["bradycardia"],"offsets":[[500,511]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"1266","type":"Chemical","text":["timolol"],"offsets":[[569,576]],"normalized":[{"db_name":"MESH","db_id":"D013999"}]},{"id":"1267","type":"Disease","text":["cardiomegaly"],"offsets":[[694,706]],"normalized":[{"db_name":"MESH","db_id":"D006332"}]},{"id":"1268","type":"Disease","text":["infarction"],"offsets":[[772,782]],"normalized":[{"db_name":"MESH","db_id":"D007238"}]},{"id":"1269","type":"Chemical","text":["timolol"],"offsets":[[856,863]],"normalized":[{"db_name":"MESH","db_id":"D013999"}]}],"events":[],"coreferences":[],"relations":[{"id":"1270","type":"CID","arg1_id":"1258","arg2_id":"1267","normalized":[]},{"id":"1271","type":"CID","arg1_id":"1260","arg2_id":"1267","normalized":[]},{"id":"1272","type":"CID","arg1_id":"1262","arg2_id":"1267","normalized":[]},{"id":"1273","type":"CID","arg1_id":"1263","arg2_id":"1267","normalized":[]},{"id":"1274","type":"CID","arg1_id":"1264","arg2_id":"1267","normalized":[]},{"id":"1275","type":"CID","arg1_id":"1266","arg2_id":"1267","normalized":[]},{"id":"1276","type":"CID","arg1_id":"1269","arg2_id":"1267","normalized":[]}]}
{"id":"1277","document_id":"6286738","passages":[{"id":"1278","type":"title","text":["Vitamin D3 toxicity in dairy cows."],"offsets":[[0,34]]},{"id":"1279","type":"abstract","text":["Large parenteral doses of vitamin D3 (15 to 17.5 x 10(6) IU vitamin D3) were associated with prolonged hypercalcemia, hyperphosphatemia, and large increases of vitamin D3 and its metabolites in the blood plasma of nonlactating nonpregnant and pregnant Jersey cows. Calcium concentrations 1 day postpartum were higher in cows treated with vitamin D3 about 32 days prepartum (8.8 mg\/100 ml) than in control cows (5.5 mg\/100 ml). None of the cows treated with vitamin D3 showed signs of milk fever during the peripartal period; however, 22% of the control cows developed clinical signs of milk fever during this period. Signs of vitamin D3 toxicity were not observed in nonlactating nonpregnant cows; however, pregnant cows commonly developed severe signs of vitamin D3 toxicity and 10 of 17 cows died. There was widespread metastatic calcification in the cows that died. Because of the extreme toxicity of vitamin D3 in pregnant Jersey cows and the low margin of safety between doses of vitamin D3 that prevent milk fever and doses that induce milk fever, we concluded that vitamin D3 cannot be used practically to prevent milk fever when injected several weeks prepartum."],"offsets":[[35,1205]]}],"entities":[{"id":"1280","type":"Chemical","text":["Vitamin D3"],"offsets":[[0,10]],"normalized":[{"db_name":"MESH","db_id":"D002762"}]},{"id":"1281","type":"Disease","text":["toxicity"],"offsets":[[11,19]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"1282","type":"Chemical","text":["vitamin D3"],"offsets":[[61,71]],"normalized":[{"db_name":"MESH","db_id":"D002762"}]},{"id":"1283","type":"Chemical","text":["vitamin 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{"id":"1325","document_id":"6287825","passages":[{"id":"1326","type":"title","text":["Diseases of peripheral nerves as seen in the Nigerian African."],"offsets":[[0,62]]},{"id":"1327","type":"abstract","text":["The anatomical and aetiological diagnoses of peripheral nerve disease excluding its primary benign and malignant disorders, as seen in 358 Nigerians are presented. There is a male preponderance and the peak incidence is in the fourth decade. Sensori-motor neuropathy was the commonest presentation (50%). Guillain-Barr   syndrome was the commonest identifiable cause (15.6%), accounting for half of the cases with motor neuropathy. Peripheral neuropathy due to nutritional deficiency of thiamine and riboflavin was common (10.1%) and presented mainly as sensory and sensori-motor neuropathy. Diabetes mellitus was the major cause of autonomic neuropathy. Isoniazid was the most frequent agent in drug-induced neuropathy. Migraine (20%) was not an uncommon cause of cranial neuropathy although malignancies arising from the reticuloendothelial system or related structures of the head and neck were more frequent (26%). In 26.5% of all the cases, the aetiology of the neuropathy was undetermined. Heredofamilial and connective tissue disorders were rare. Some of the factors related to the clinical presentation and pathogenesis of the neuropathies are briefly discussed."],"offsets":[[63,1233]]}],"entities":[{"id":"1328","type":"Disease","text":["Diseases of peripheral nerves"],"offsets":[[0,29]],"normalized":[{"db_name":"MESH","db_id":"D010523"}]},{"id":"1329","type":"Disease","text":["peripheral nerve disease"],"offsets":[[108,132]],"normalized":[{"db_name":"MESH","db_id":"D010523"}]},{"id":"1330","type":"Disease","text":["Sensori-motor neuropathy"],"offsets":[[305,329]],"normalized":[{"db_name":"MESH","db_id":"D010523"}]},{"id":"1331","type":"Disease","text":["Guillain-Barr   syndrome"],"offsets":[[368,392]],"normalized":[{"db_name":"MESH","db_id":"D020275"}]},{"id":"1332","type":"Disease","text":["motor neuropathy"],"offsets":[[477,493]],"normalized":[{"db_name":"MESH","db_id":"D010523"}]},{"id":"1333","type":"Disease","text":["Peripheral neuropathy"],"offsets":[[495,516]],"normalized":[{"db_name":"MESH","db_id":"D010523"}]},{"id":"1334","type":"Disease","text":["nutritional deficiency"],"offsets":[[524,546]],"normalized":[{"db_name":"MESH","db_id":"D044342"}]},{"id":"1335","type":"Chemical","text":["thiamine"],"offsets":[[550,558]],"normalized":[{"db_name":"MESH","db_id":"D013831"}]},{"id":"1336","type":"Chemical","text":["riboflavin"],"offsets":[[563,573]],"normalized":[{"db_name":"MESH","db_id":"D012256"}]},{"id":"1337","type":"Disease","text":["sensori-motor neuropathy"],"offsets":[[629,653]],"normalized":[{"db_name":"MESH","db_id":"D010523"}]},{"id":"1338","type":"Disease","text":["Diabetes mellitus"],"offsets":[[655,672]],"normalized":[{"db_name":"MESH","db_id":"D003920"}]},{"id":"1339","type":"Disease","text":["autonomic neuropathy"],"offsets":[[696,716]],"normalized":[{"db_name":"MESH","db_id":"D009422"}]},{"id":"1340","type":"Chemical","text":["Isoniazid"],"offsets":[[718,727]],"normalized":[{"db_name":"MESH","db_id":"D007538"}]},{"id":"1341","type":"Disease","text":["neuropathy"],"offsets":[[772,782]],"normalized":[{"db_name":"MESH","db_id":"D009422"}]},{"id":"1342","type":"Disease","text":["Migraine"],"offsets":[[784,792]],"normalized":[{"db_name":"MESH","db_id":"D008881"}]},{"id":"1343","type":"Disease","text":["cranial neuropathy"],"offsets":[[828,846]],"normalized":[{"db_name":"MESH","db_id":"D003389"}]},{"id":"1344","type":"Disease","text":["malignancies"],"offsets":[[856,868]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"1345","type":"Disease","text":["neuropathy"],"offsets":[[1030,1040]],"normalized":[{"db_name":"MESH","db_id":"D009422"}]},{"id":"1346","type":"Disease","text":["connective tissue disorders"],"offsets":[[1078,1105]],"normalized":[{"db_name":"MESH","db_id":"D003240"}]},{"id":"1347","type":"Disease","text":["neuropathies"],"offsets":[[1198,1210]],"normalized":[{"db_name":"MESH","db_id":"D009422"}]}],"events":[],"coreferences":[],"relations":[{"id":"1348","type":"CID","arg1_id":"1336","arg2_id":"1328","normalized":[]},{"id":"1349","type":"CID","arg1_id":"1336","arg2_id":"1329","normalized":[]},{"id":"1350","type":"CID","arg1_id":"1336","arg2_id":"1330","normalized":[]},{"id":"1351","type":"CID","arg1_id":"1336","arg2_id":"1332","normalized":[]},{"id":"1352","type":"CID","arg1_id":"1336","arg2_id":"1333","normalized":[]},{"id":"1353","type":"CID","arg1_id":"1336","arg2_id":"1337","normalized":[]},{"id":"1354","type":"CID","arg1_id":"1335","arg2_id":"1328","normalized":[]},{"id":"1355","type":"CID","arg1_id":"1335","arg2_id":"1329","normalized":[]},{"id":"1356","type":"CID","arg1_id":"1335","arg2_id":"1330","normalized":[]},{"id":"1357","type":"CID","arg1_id":"1335","arg2_id":"1332","normalized":[]},{"id":"1358","type":"CID","arg1_id":"1335","arg2_id":"1333","normalized":[]},{"id":"1359","type":"CID","arg1_id":"1335","arg2_id":"1337","normalized":[]},{"id":"1360","type":"CID","arg1_id":"1340","arg2_id":"1328","normalized":[]},{"id":"1361","type":"CID","arg1_id":"1340","arg2_id":"1329","normalized":[]},{"id":"1362","type":"CID","arg1_id":"1340","arg2_id":"1330","normalized":[]},{"id":"1363","type":"CID","arg1_id":"1340","arg2_id":"1332","normalized":[]},{"id":"1364","type":"CID","arg1_id":"1340","arg2_id":"1333","normalized":[]},{"id":"1365","type":"CID","arg1_id":"1340","arg2_id":"1337","normalized":[]}]}
{"id":"1366","document_id":"6386793","passages":[{"id":"1367","type":"title","text":["A double-blind study of the efficacy and safety of dothiepin hydrochloride in the treatment of major depressive disorder."],"offsets":[[0,121]]},{"id":"1368","type":"abstract","text":["In a 6-week double-blind parallel treatment study, dothiepin and amitriptyline were compared to placebo in the treatment of 33 depressed outpatients. Dothiepin and amitriptyline were equally effective in alleviating the symptoms of depressive illness, and both were significantly superior to placebo. The overall incidence of side effects and the frequency and severity of blurred vision, dry mouth, and drowsiness were significantly less with dothiepin than with amitriptyline. Dothiepin also produced fewer CNS and cardiovascular effects. There were no clinically important changes in laboratory parameters. Dothiepin thus was found to be an effective antidepressant drug associated with fewer side effects than amitriptyline in the treatment of depressed outpatients."],"offsets":[[122,892]]}],"entities":[{"id":"1369","type":"Chemical","text":["dothiepin hydrochloride"],"offsets":[[51,74]],"normalized":[{"db_name":"MESH","db_id":"D004308"}]},{"id":"1370","type":"Disease","text":["depressive disorder"],"offsets":[[101,120]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"1371","type":"Chemical","text":["dothiepin"],"offsets":[[173,182]],"normalized":[{"db_name":"MESH","db_id":"D004308"}]},{"id":"1372","type":"Chemical","text":["amitriptyline"],"offsets":[[187,200]],"normalized":[{"db_name":"MESH","db_id":"D000639"}]},{"id":"1373","type":"Disease","text":["depressed"],"offsets":[[249,258]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"1374","type":"Chemical","text":["Dothiepin"],"offsets":[[272,281]],"normalized":[{"db_name":"MESH","db_id":"D004308"}]},{"id":"1375","type":"Chemical","text":["amitriptyline"],"offsets":[[286,299]],"normalized":[{"db_name":"MESH","db_id":"D000639"}]},{"id":"1376","type":"Disease","text":["depressive illness"],"offsets":[[354,372]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"1377","type":"Disease","text":["blurred vision"],"offsets":[[495,509]],"normalized":[{"db_name":"MESH","db_id":"D014786"}]},{"id":"1378","type":"Disease","text":["dry mouth"],"offsets":[[511,520]],"normalized":[{"db_name":"MESH","db_id":"D014987"}]},{"id":"1379","type":"Chemical","text":["dothiepin"],"offsets":[[566,575]],"normalized":[{"db_name":"MESH","db_id":"D004308"}]},{"id":"1380","type":"Chemical","text":["amitriptyline"],"offsets":[[586,599]],"normalized":[{"db_name":"MESH","db_id":"D000639"}]},{"id":"1381","type":"Chemical","text":["Dothiepin"],"offsets":[[601,610]],"normalized":[{"db_name":"MESH","db_id":"D004308"}]},{"id":"1382","type":"Chemical","text":["Dothiepin"],"offsets":[[732,741]],"normalized":[{"db_name":"MESH","db_id":"D004308"}]},{"id":"1383","type":"Chemical","text":["antidepressant"],"offsets":[[776,790]],"normalized":[{"db_name":"MESH","db_id":"D000928"}]},{"id":"1384","type":"Chemical","text":["amitriptyline"],"offsets":[[836,849]],"normalized":[{"db_name":"MESH","db_id":"D000639"}]},{"id":"1385","type":"Disease","text":["depressed"],"offsets":[[870,879]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]}],"events":[],"coreferences":[],"relations":[{"id":"1386","type":"CID","arg1_id":"1372","arg2_id":"1377","normalized":[]},{"id":"1387","type":"CID","arg1_id":"1375","arg2_id":"1377","normalized":[]},{"id":"1388","type":"CID","arg1_id":"1380","arg2_id":"1377","normalized":[]},{"id":"1389","type":"CID","arg1_id":"1384","arg2_id":"1377","normalized":[]},{"id":"1390","type":"CID","arg1_id":"1372","arg2_id":"1378","normalized":[]},{"id":"1391","type":"CID","arg1_id":"1375","arg2_id":"1378","normalized":[]},{"id":"1392","type":"CID","arg1_id":"1380","arg2_id":"1378","normalized":[]},{"id":"1393","type":"CID","arg1_id":"1384","arg2_id":"1378","normalized":[]}]}
{"id":"1394","document_id":"6387529","passages":[{"id":"1395","type":"title","text":["Behavioral effects of diazepam and propranolol in patients with panic disorder and agoraphobia."],"offsets":[[0,95]]},{"id":"1396","type":"abstract","text":["The effects of oral doses of diazepam (single dose of 10 mg and a median dose of 30 mg\/day for 2 weeks) and propranolol (single dose of 80 mg and a median dose of 240 mg\/day for 2 weeks) on psychological performance of patients with panic disorders and agoraphobia were investigated in a double-blind, randomized and crossover design. Both drugs impaired immediate free recall but the decrease was greater for diazepam than propranolol. Delayed free recall was also impaired but the two drugs did not differ. Patients tapped faster after propranolol than diazepam and they were more sedated after diazepam than propranolol. After 2 weeks of treatment, patients tested 5-8 h after the last dose of medication did not show any decrement of performance. These results are similar to those previously found in healthy subjects. Accumulation of drugs was not reflected in prolonged behavioral impairment."],"offsets":[[96,995]]}],"entities":[{"id":"1397","type":"Chemical","text":["diazepam"],"offsets":[[22,30]],"normalized":[{"db_name":"MESH","db_id":"D003975"}]},{"id":"1398","type":"Chemical","text":["propranolol"],"offsets":[[35,46]],"normalized":[{"db_name":"MESH","db_id":"D011433"}]},{"id":"1399","type":"Disease","text":["panic disorder"],"offsets":[[64,78]],"normalized":[{"db_name":"MESH","db_id":"D016584"}]},{"id":"1400","type":"Disease","text":["agoraphobia"],"offsets":[[83,94]],"normalized":[{"db_name":"MESH","db_id":"D000379"}]},{"id":"1401","type":"Chemical","text":["diazepam"],"offsets":[[125,133]],"normalized":[{"db_name":"MESH","db_id":"D003975"}]},{"id":"1402","type":"Chemical","text":["propranolol"],"offsets":[[204,215]],"normalized":[{"db_name":"MESH","db_id":"D011433"}]},{"id":"1403","type":"Disease","text":["panic disorders"],"offsets":[[329,344]],"normalized":[{"db_name":"MESH","db_id":"D016584"}]},{"id":"1404","type":"Disease","text":["agoraphobia"],"offsets":[[349,360]],"normalized":[{"db_name":"MESH","db_id":"D000379"}]},{"id":"1405","type":"Disease","text":["impaired immediate free recall"],"offsets":[[442,472]],"normalized":[{"db_name":"MESH","db_id":"D008569"}]},{"id":"1406","type":"Chemical","text":["diazepam"],"offsets":[[506,514]],"normalized":[{"db_name":"MESH","db_id":"D003975"}]},{"id":"1407","type":"Chemical","text":["propranolol"],"offsets":[[520,531]],"normalized":[{"db_name":"MESH","db_id":"D011433"}]},{"id":"1408","type":"Disease","text":["Delayed free recall was also impaired"],"offsets":[[533,570]],"normalized":[{"db_name":"MESH","db_id":"D008569"}]},{"id":"1409","type":"Chemical","text":["propranolol"],"offsets":[[634,645]],"normalized":[{"db_name":"MESH","db_id":"D011433"}]},{"id":"1410","type":"Chemical","text":["diazepam"],"offsets":[[651,659]],"normalized":[{"db_name":"MESH","db_id":"D003975"}]},{"id":"1411","type":"Chemical","text":["diazepam"],"offsets":[[693,701]],"normalized":[{"db_name":"MESH","db_id":"D003975"}]},{"id":"1412","type":"Chemical","text":["propranolol"],"offsets":[[707,718]],"normalized":[{"db_name":"MESH","db_id":"D011433"}]},{"id":"1413","type":"Disease","text":["behavioral impairment"],"offsets":[[973,994]],"normalized":[{"db_name":"MESH","db_id":"D001523"}]}],"events":[],"coreferences":[],"relations":[{"id":"1414","type":"CID","arg1_id":"1398","arg2_id":"1405","normalized":[]},{"id":"1415","type":"CID","arg1_id":"1398","arg2_id":"1408","normalized":[]},{"id":"1416","type":"CID","arg1_id":"1402","arg2_id":"1405","normalized":[]},{"id":"1417","type":"CID","arg1_id":"1402","arg2_id":"1408","normalized":[]},{"id":"1418","type":"CID","arg1_id":"1407","arg2_id":"1405","normalized":[]},{"id":"1419","type":"CID","arg1_id":"1407","arg2_id":"1408","normalized":[]},{"id":"1420","type":"CID","arg1_id":"1409","arg2_id":"1405","normalized":[]},{"id":"1421","type":"CID","arg1_id":"1409","arg2_id":"1408","normalized":[]},{"id":"1422","type":"CID","arg1_id":"1412","arg2_id":"1405","normalized":[]},{"id":"1423","type":"CID","arg1_id":"1412","arg2_id":"1408","normalized":[]},{"id":"1424","type":"CID","arg1_id":"1397","arg2_id":"1405","normalized":[]},{"id":"1425","type":"CID","arg1_id":"1397","arg2_id":"1408","normalized":[]},{"id":"1426","type":"CID","arg1_id":"1401","arg2_id":"1405","normalized":[]},{"id":"1427","type":"CID","arg1_id":"1401","arg2_id":"1408","normalized":[]},{"id":"1428","type":"CID","arg1_id":"1406","arg2_id":"1405","normalized":[]},{"id":"1429","type":"CID","arg1_id":"1406","arg2_id":"1408","normalized":[]},{"id":"1430","type":"CID","arg1_id":"1410","arg2_id":"1405","normalized":[]},{"id":"1431","type":"CID","arg1_id":"1410","arg2_id":"1408","normalized":[]},{"id":"1432","type":"CID","arg1_id":"1411","arg2_id":"1405","normalized":[]},{"id":"1433","type":"CID","arg1_id":"1411","arg2_id":"1408","normalized":[]}]}
{"id":"1434","document_id":"6692345","passages":[{"id":"1435","type":"title","text":["Effect of aspirin on N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide-induced epithelial proliferation in the urinary bladder and forestomach of the rat."],"offsets":[[0,150]]},{"id":"1436","type":"abstract","text":["The co-administration of aspirin with N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide (FANFT) to rats resulted in a reduced incidence of FANFT-induced bladder carcinomas but a concomitant induction of forestomach tumors. An autoradiographic study was performed on male F-344 rats fed diet containing FANFT at a level of 0.2% and\/or aspirin at a level of 0.5% to evaluate the effect of aspirin on the increased cell proliferation induced by FANFT in the forestomach and bladder. FANFT-induced cell proliferation in the bladder was significantly suppressed by aspirin co-administration after 4 weeks but not after 12 weeks. In the forestomach, and also in the liver, aspirin did not affect the FANFT-induced increase in labeling index. The present results are consistent with the carcinogenicity experiment suggesting that different mechanisms are involved in FANFT carcinogenesis in the bladder and forestomach, and that aspirin's effect on FANFT in the forestomach is not due to an irritant effect associated with increased cell proliferation. Also, there appears to be an adaptation by the rats to the chronic ingestion of aspirin."],"offsets":[[151,1281]]}],"entities":[{"id":"1437","type":"Chemical","text":["aspirin"],"offsets":[[10,17]],"normalized":[{"db_name":"MESH","db_id":"D001241"}]},{"id":"1438","type":"Chemical","text":["N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide"],"offsets":[[21,66]],"normalized":[{"db_name":"MESH","db_id":"D005200"}]},{"id":"1439","type":"Chemical","text":["aspirin"],"offsets":[[176,183]],"normalized":[{"db_name":"MESH","db_id":"D001241"}]},{"id":"1440","type":"Chemical","text":["N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide"],"offsets":[[189,234]],"normalized":[{"db_name":"MESH","db_id":"D005200"}]},{"id":"1441","type":"Chemical","text":["FANFT"],"offsets":[[236,241]],"normalized":[{"db_name":"MESH","db_id":"D005200"}]},{"id":"1442","type":"Chemical","text":["FANFT"],"offsets":[[286,291]],"normalized":[{"db_name":"MESH","db_id":"D005200"}]},{"id":"1443","type":"Disease","text":["bladder carcinomas"],"offsets":[[300,318]],"normalized":[{"db_name":"MESH","db_id":"D001749"}]},{"id":"1444","type":"Disease","text":["forestomach tumors"],"offsets":[[350,368]],"normalized":[{"db_name":"MESH","db_id":"D013274"}]},{"id":"1445","type":"Chemical","text":["FANFT"],"offsets":[[449,454]],"normalized":[{"db_name":"MESH","db_id":"D005200"}]},{"id":"1446","type":"Chemical","text":["aspirin"],"offsets":[[481,488]],"normalized":[{"db_name":"MESH","db_id":"D001241"}]},{"id":"1447","type":"Chemical","text":["aspirin"],"offsets":[[534,541]],"normalized":[{"db_name":"MESH","db_id":"D001241"}]},{"id":"1448","type":"Chemical","text":["FANFT"],"offsets":[[589,594]],"normalized":[{"db_name":"MESH","db_id":"D005200"}]},{"id":"1449","type":"Chemical","text":["FANFT"],"offsets":[[627,632]],"normalized":[{"db_name":"MESH","db_id":"D005200"}]},{"id":"1450","type":"Chemical","text":["aspirin"],"offsets":[[707,714]],"normalized":[{"db_name":"MESH","db_id":"D001241"}]},{"id":"1451","type":"Chemical","text":["aspirin"],"offsets":[[814,821]],"normalized":[{"db_name":"MESH","db_id":"D001241"}]},{"id":"1452","type":"Chemical","text":["FANFT"],"offsets":[[841,846]],"normalized":[{"db_name":"MESH","db_id":"D005200"}]},{"id":"1453","type":"Chemical","text":["FANFT"],"offsets":[[1007,1012]],"normalized":[{"db_name":"MESH","db_id":"D005200"}]},{"id":"1454","type":"Disease","text":["carcinogenesis"],"offsets":[[1013,1027]],"normalized":[{"db_name":"MESH","db_id":"D063646"}]},{"id":"1455","type":"Chemical","text":["aspirin"],"offsets":[[1069,1076]],"normalized":[{"db_name":"MESH","db_id":"D001241"}]},{"id":"1456","type":"Chemical","text":["FANFT"],"offsets":[[1089,1094]],"normalized":[{"db_name":"MESH","db_id":"D005200"}]},{"id":"1457","type":"Chemical","text":["aspirin"],"offsets":[[1273,1280]],"normalized":[{"db_name":"MESH","db_id":"D001241"}]}],"events":[],"coreferences":[],"relations":[{"id":"1458","type":"CID","arg1_id":"1438","arg2_id":"1443","normalized":[]},{"id":"1459","type":"CID","arg1_id":"1440","arg2_id":"1443","normalized":[]},{"id":"1460","type":"CID","arg1_id":"1441","arg2_id":"1443","normalized":[]},{"id":"1461","type":"CID","arg1_id":"1442","arg2_id":"1443","normalized":[]},{"id":"1462","type":"CID","arg1_id":"1445","arg2_id":"1443","normalized":[]},{"id":"1463","type":"CID","arg1_id":"1448","arg2_id":"1443","normalized":[]},{"id":"1464","type":"CID","arg1_id":"1449","arg2_id":"1443","normalized":[]},{"id":"1465","type":"CID","arg1_id":"1452","arg2_id":"1443","normalized":[]},{"id":"1466","type":"CID","arg1_id":"1453","arg2_id":"1443","normalized":[]},{"id":"1467","type":"CID","arg1_id":"1456","arg2_id":"1443","normalized":[]},{"id":"1468","type":"CID","arg1_id":"1438","arg2_id":"1444","normalized":[]},{"id":"1469","type":"CID","arg1_id":"1440","arg2_id":"1444","normalized":[]},{"id":"1470","type":"CID","arg1_id":"1441","arg2_id":"1444","normalized":[]},{"id":"1471","type":"CID","arg1_id":"1442","arg2_id":"1444","normalized":[]},{"id":"1472","type":"CID","arg1_id":"1445","arg2_id":"1444","normalized":[]},{"id":"1473","type":"CID","arg1_id":"1448","arg2_id":"1444","normalized":[]},{"id":"1474","type":"CID","arg1_id":"1449","arg2_id":"1444","normalized":[]},{"id":"1475","type":"CID","arg1_id":"1452","arg2_id":"1444","normalized":[]},{"id":"1476","type":"CID","arg1_id":"1453","arg2_id":"1444","normalized":[]},{"id":"1477","type":"CID","arg1_id":"1456","arg2_id":"1444","normalized":[]}]}
{"id":"1478","document_id":"6773726","passages":[{"id":"1479","type":"title","text":["Provocation of postural hypotension by nitroglycerin in diabetic autonomic neuropathy?"],"offsets":[[0,86]]},{"id":"1480","type":"abstract","text":["The effect of nitroglycerin on heart rate and systolic blood pressure was compared in 5 normal subjects, 12 diabetic subjects without autonomic neuropathy, and 5 diabetic subjects with autonomic neuropathy. The magnitude and time course of the increase in heart rate and the decrease in systolic blood pressure after nitroglycerin were similar in the normal and diabetic subjects without autonomic neuropathy, whereas a lesser increase in heart rate and a greater decrease in systolic blood pressure occurred in the diabetic subjects with autonomic neuropathy. It is therefore suggested that caution should be exercised when prescribing vasodilator drugs in diabetic patients, particularly those with autonomic neuropathy."],"offsets":[[87,809]]}],"entities":[{"id":"1481","type":"Disease","text":["hypotension"],"offsets":[[24,35]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"1482","type":"Chemical","text":["nitroglycerin"],"offsets":[[39,52]],"normalized":[{"db_name":"MESH","db_id":"D005996"}]},{"id":"1483","type":"Disease","text":["diabetic autonomic neuropathy"],"offsets":[[56,85]],"normalized":[{"db_name":"MESH","db_id":"D003929"}]},{"id":"1484","type":"Chemical","text":["nitroglycerin"],"offsets":[[101,114]],"normalized":[{"db_name":"MESH","db_id":"D005996"}]},{"id":"1485","type":"Disease","text":["diabetic"],"offsets":[[195,203]],"normalized":[{"db_name":"MESH","db_id":"D003920"}]},{"id":"1486","type":"Disease","text":["autonomic neuropathy"],"offsets":[[221,241]],"normalized":[{"db_name":"MESH","db_id":"D009422"}]},{"id":"1487","type":"Disease","text":["diabetic"],"offsets":[[249,257]],"normalized":[{"db_name":"MESH","db_id":"D003920"}]},{"id":"1488","type":"Disease","text":["autonomic neuropathy"],"offsets":[[272,292]],"normalized":[{"db_name":"MESH","db_id":"D009422"}]},{"id":"1489","type":"Chemical","text":["nitroglycerin"],"offsets":[[404,417]],"normalized":[{"db_name":"MESH","db_id":"D005996"}]},{"id":"1490","type":"Disease","text":["diabetic"],"offsets":[[449,457]],"normalized":[{"db_name":"MESH","db_id":"D003920"}]},{"id":"1491","type":"Disease","text":["autonomic neuropathy"],"offsets":[[475,495]],"normalized":[{"db_name":"MESH","db_id":"D009422"}]},{"id":"1492","type":"Disease","text":["diabetic"],"offsets":[[603,611]],"normalized":[{"db_name":"MESH","db_id":"D003920"}]},{"id":"1493","type":"Disease","text":["autonomic neuropathy"],"offsets":[[626,646]],"normalized":[{"db_name":"MESH","db_id":"D009422"}]},{"id":"1494","type":"Disease","text":["diabetic"],"offsets":[[745,753]],"normalized":[{"db_name":"MESH","db_id":"D003920"}]},{"id":"1495","type":"Disease","text":["autonomic neuropathy"],"offsets":[[788,808]],"normalized":[{"db_name":"MESH","db_id":"D009422"}]}],"events":[],"coreferences":[],"relations":[{"id":"1496","type":"CID","arg1_id":"1482","arg2_id":"1481","normalized":[]},{"id":"1497","type":"CID","arg1_id":"1484","arg2_id":"1481","normalized":[]},{"id":"1498","type":"CID","arg1_id":"1489","arg2_id":"1481","normalized":[]}]}
{"id":"1499","document_id":"6888657","passages":[{"id":"1500","type":"title","text":["Characterization of estrogen-induced adenohypophyseal tumors in the Fischer 344 rat."],"offsets":[[0,84]]},{"id":"1501","type":"abstract","text":["Pituitary tumors were induced in F344 female rats by chronic treatment with diethylstilbestrol (DES, 8-10 mg) implanted subcutaneously in silastic capsules. Over a range of 1-150 days of DES treatment, pairs of control and DES-treated rats were sacrificed, and their pituitaries dissociated enzymatically into single-cell preparations. The cell populations were examined regarding total cell recovery correlated with gland weight, intracellular prolactin (PRL) content and subsequent release in primary culture, immunocytochemical PRL staining, density and\/or size alterations via separation on Ficoll-Hypaque and by unit gravity sedimentation, and cell cycle analysis, after acriflavine DNA staining, by laser flow cytometry. Total cell yields from DES-treated pituitaries increased from 1.3 times control yields at 8 days of treatment to 58.9 times control values by day 150. Intracellular PRL content ranged from 1.9 to 9.4 times control levels, and PRL release in vitro was significantly and consistently higher than controls, after at least 8 days of DES exposure. Beyond 8 days of DES exposure, the immunochemically PRL-positive proportion of cells increased to over 50% of the total population. Increased density and\/or size and PRL content were indicated for the majority of the PRL cell population in both types of separation protocols. All these effects of DES were more pronounced among previously ovariectomized animals. The data extend the findings of other investigators, further establishing the DES-induced tumor as a model for study of PRL cellular control mechanisms."],"offsets":[[85,1670]]}],"entities":[{"id":"1502","type":"Chemical","text":["estrogen"],"offsets":[[20,28]],"normalized":[{"db_name":"MESH","db_id":"D004967"}]},{"id":"1503","type":"Disease","text":["adenohypophyseal tumors"],"offsets":[[37,60]],"normalized":[{"db_name":"MESH","db_id":"D010911"}]},{"id":"1504","type":"Disease","text":["Pituitary tumors"],"offsets":[[85,101]],"normalized":[{"db_name":"MESH","db_id":"D010911"}]},{"id":"1505","type":"Chemical","text":["diethylstilbestrol"],"offsets":[[161,179]],"normalized":[{"db_name":"MESH","db_id":"D004054"}]},{"id":"1506","type":"Chemical","text":["DES"],"offsets":[[181,184]],"normalized":[{"db_name":"MESH","db_id":"D004054"}]},{"id":"1507","type":"Chemical","text":["DES"],"offsets":[[272,275]],"normalized":[{"db_name":"MESH","db_id":"D004054"}]},{"id":"1508","type":"Chemical","text":["DES"],"offsets":[[308,311]],"normalized":[{"db_name":"MESH","db_id":"D004054"}]},{"id":"1509","type":"Chemical","text":["acriflavine"],"offsets":[[761,772]],"normalized":[{"db_name":"MESH","db_id":"D000167"}]},{"id":"1510","type":"Chemical","text":["DES"],"offsets":[[835,838]],"normalized":[{"db_name":"MESH","db_id":"D004054"}]},{"id":"1511","type":"Chemical","text":["DES"],"offsets":[[1141,1144]],"normalized":[{"db_name":"MESH","db_id":"D004054"}]},{"id":"1512","type":"Chemical","text":["DES"],"offsets":[[1172,1175]],"normalized":[{"db_name":"MESH","db_id":"D004054"}]},{"id":"1513","type":"Chemical","text":["DES"],"offsets":[[1452,1455]],"normalized":[{"db_name":"MESH","db_id":"D004054"}]},{"id":"1514","type":"Chemical","text":["DES"],"offsets":[[1596,1599]],"normalized":[{"db_name":"MESH","db_id":"D004054"}]},{"id":"1515","type":"Disease","text":["tumor"],"offsets":[[1608,1613]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]}],"events":[],"coreferences":[],"relations":[{"id":"1516","type":"CID","arg1_id":"1505","arg2_id":"1503","normalized":[]},{"id":"1517","type":"CID","arg1_id":"1505","arg2_id":"1504","normalized":[]},{"id":"1518","type":"CID","arg1_id":"1506","arg2_id":"1503","normalized":[]},{"id":"1519","type":"CID","arg1_id":"1506","arg2_id":"1504","normalized":[]},{"id":"1520","type":"CID","arg1_id":"1507","arg2_id":"1503","normalized":[]},{"id":"1521","type":"CID","arg1_id":"1507","arg2_id":"1504","normalized":[]},{"id":"1522","type":"CID","arg1_id":"1508","arg2_id":"1503","normalized":[]},{"id":"1523","type":"CID","arg1_id":"1508","arg2_id":"1504","normalized":[]},{"id":"1524","type":"CID","arg1_id":"1510","arg2_id":"1503","normalized":[]},{"id":"1525","type":"CID","arg1_id":"1510","arg2_id":"1504","normalized":[]},{"id":"1526","type":"CID","arg1_id":"1511","arg2_id":"1503","normalized":[]},{"id":"1527","type":"CID","arg1_id":"1511","arg2_id":"1504","normalized":[]},{"id":"1528","type":"CID","arg1_id":"1512","arg2_id":"1503","normalized":[]},{"id":"1529","type":"CID","arg1_id":"1512","arg2_id":"1504","normalized":[]},{"id":"1530","type":"CID","arg1_id":"1513","arg2_id":"1503","normalized":[]},{"id":"1531","type":"CID","arg1_id":"1513","arg2_id":"1504","normalized":[]},{"id":"1532","type":"CID","arg1_id":"1514","arg2_id":"1503","normalized":[]},{"id":"1533","type":"CID","arg1_id":"1514","arg2_id":"1504","normalized":[]}]}
{"id":"1534","document_id":"7265370","passages":[{"id":"1535","type":"title","text":["Triamterene nephrolithiasis complicating dyazide therapy."],"offsets":[[0,57]]},{"id":"1536","type":"abstract","text":["A case of triamterene nephrolithiasis is reported in a man after 4 years of hydrochlorothiazide-triamterene therapy for hypertension. The stone passed spontaneously and was found to contain a triamterene metabolite admixed with uric acid salts. Factors affecting triamterene nephrolithiasis are discussed and 2 previously reported cases are reviewed."],"offsets":[[58,408]]}],"entities":[{"id":"1537","type":"Chemical","text":["Triamterene"],"offsets":[[0,11]],"normalized":[{"db_name":"MESH","db_id":"D014223"}]},{"id":"1538","type":"Disease","text":["nephrolithiasis"],"offsets":[[12,27]],"normalized":[{"db_name":"MESH","db_id":"D053040"}]},{"id":"1539","type":"Chemical","text":["dyazide"],"offsets":[[41,48]],"normalized":[{"db_name":"MESH","db_id":"C020743"}]},{"id":"1540","type":"Chemical","text":["triamterene"],"offsets":[[68,79]],"normalized":[{"db_name":"MESH","db_id":"D014223"}]},{"id":"1541","type":"Disease","text":["nephrolithiasis"],"offsets":[[80,95]],"normalized":[{"db_name":"MESH","db_id":"D053040"}]},{"id":"1542","type":"Chemical","text":["hydrochlorothiazide-triamterene"],"offsets":[[134,165]],"normalized":[{"db_name":"MESH","db_id":"C020743"}]},{"id":"1543","type":"Disease","text":["hypertension"],"offsets":[[178,190]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"1544","type":"Chemical","text":["triamterene"],"offsets":[[250,261]],"normalized":[{"db_name":"MESH","db_id":"D014223"}]},{"id":"1545","type":"Chemical","text":["uric acid salts"],"offsets":[[286,301]],"normalized":[{"db_name":"MESH","db_id":"D014527"},{"db_name":"MESH","db_id":"D012492"}]},{"id":"1546","type":"Chemical","text":["triamterene"],"offsets":[[321,332]],"normalized":[{"db_name":"MESH","db_id":"D014223"}]},{"id":"1547","type":"Disease","text":["nephrolithiasis"],"offsets":[[333,348]],"normalized":[{"db_name":"MESH","db_id":"D053040"}]}],"events":[],"coreferences":[],"relations":[{"id":"1548","type":"CID","arg1_id":"1537","arg2_id":"1538","normalized":[]},{"id":"1549","type":"CID","arg1_id":"1537","arg2_id":"1541","normalized":[]},{"id":"1550","type":"CID","arg1_id":"1537","arg2_id":"1547","normalized":[]},{"id":"1551","type":"CID","arg1_id":"1540","arg2_id":"1538","normalized":[]},{"id":"1552","type":"CID","arg1_id":"1540","arg2_id":"1541","normalized":[]},{"id":"1553","type":"CID","arg1_id":"1540","arg2_id":"1547","normalized":[]},{"id":"1554","type":"CID","arg1_id":"1544","arg2_id":"1538","normalized":[]},{"id":"1555","type":"CID","arg1_id":"1544","arg2_id":"1541","normalized":[]},{"id":"1556","type":"CID","arg1_id":"1544","arg2_id":"1547","normalized":[]},{"id":"1557","type":"CID","arg1_id":"1546","arg2_id":"1538","normalized":[]},{"id":"1558","type":"CID","arg1_id":"1546","arg2_id":"1541","normalized":[]},{"id":"1559","type":"CID","arg1_id":"1546","arg2_id":"1547","normalized":[]}]}
{"id":"1560","document_id":"7423039","passages":[{"id":"1561","type":"title","text":["Metabolic involvement in adriamycin cardiotoxicity."],"offsets":[[0,51]]},{"id":"1562","type":"abstract","text":["The cardiotoxic effects of adriamycin were studied in mammalian myocardial cells in culture as a model system. Adriamycin inhibited cell growth and the rhythmic contractions characteristic of myocardial cells in culture. A possible involvement of energy metabolism was suggested previously, and in this study the adenylate energy charge and phosphorylcreatine mole fraction were determined in the adriamycin-treated cells. The adenylate energy charge was found to be significantly decreased, while the phophorylcreatine mole fraction was unchanged. Such disparity suggests an inhibition of creatine phosphokinase. The addition of 1 mM adenosine to the myocardial cell cultures markedly increases the ATP concentration through a pathway reportedly leading to a compartmentalized ATP pool. In the adriamycin-treated cells, the addition of adenosine increased the adenylate charge and, concomitant with this inrcease, the cells' functional integrity, in terms of percentage of beating cells and rate of contractions, was maintained."],"offsets":[[52,1081]]}],"entities":[{"id":"1563","type":"Chemical","text":["adriamycin"],"offsets":[[25,35]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"1564","type":"Disease","text":["cardiotoxicity"],"offsets":[[36,50]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"1565","type":"Disease","text":["cardiotoxic"],"offsets":[[56,67]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"1566","type":"Chemical","text":["adriamycin"],"offsets":[[79,89]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"1567","type":"Chemical","text":["Adriamycin"],"offsets":[[163,173]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"1568","type":"Chemical","text":["phosphorylcreatine"],"offsets":[[393,411]],"normalized":[{"db_name":"MESH","db_id":"D010725"}]},{"id":"1569","type":"Chemical","text":["adriamycin"],"offsets":[[449,459]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"1570","type":"Chemical","text":["phophorylcreatine"],"offsets":[[554,571]],"normalized":[{"db_name":"MESH","db_id":"D010725"}]},{"id":"1571","type":"Chemical","text":["creatine"],"offsets":[[642,650]],"normalized":[{"db_name":"MESH","db_id":"D003401"}]},{"id":"1572","type":"Chemical","text":["adenosine"],"offsets":[[687,696]],"normalized":[{"db_name":"MESH","db_id":"D000241"}]},{"id":"1573","type":"Chemical","text":["ATP"],"offsets":[[752,755]],"normalized":[{"db_name":"MESH","db_id":"D000255"}]},{"id":"1574","type":"Chemical","text":["ATP"],"offsets":[[830,833]],"normalized":[{"db_name":"MESH","db_id":"D000255"}]},{"id":"1575","type":"Chemical","text":["adriamycin"],"offsets":[[847,857]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"1576","type":"Chemical","text":["adenosine"],"offsets":[[889,898]],"normalized":[{"db_name":"MESH","db_id":"D000241"}]}],"events":[],"coreferences":[],"relations":[{"id":"1577","type":"CID","arg1_id":"1563","arg2_id":"1564","normalized":[]},{"id":"1578","type":"CID","arg1_id":"1563","arg2_id":"1565","normalized":[]},{"id":"1579","type":"CID","arg1_id":"1566","arg2_id":"1564","normalized":[]},{"id":"1580","type":"CID","arg1_id":"1566","arg2_id":"1565","normalized":[]},{"id":"1581","type":"CID","arg1_id":"1567","arg2_id":"1564","normalized":[]},{"id":"1582","type":"CID","arg1_id":"1567","arg2_id":"1565","normalized":[]},{"id":"1583","type":"CID","arg1_id":"1569","arg2_id":"1564","normalized":[]},{"id":"1584","type":"CID","arg1_id":"1569","arg2_id":"1565","normalized":[]},{"id":"1585","type":"CID","arg1_id":"1575","arg2_id":"1564","normalized":[]},{"id":"1586","type":"CID","arg1_id":"1575","arg2_id":"1565","normalized":[]}]}
{"id":"1587","document_id":"7444978","passages":[{"id":"1588","type":"title","text":["Age-dependent sensitivity of the rat to neurotoxic effects of streptomycin."],"offsets":[[0,75]]},{"id":"1589","type":"abstract","text":["Streptomycin sulfate (300 mg\/kg s.c.) was injected for various periods into preweanling rats and for 3 weeks into weanling rats. Beginning at 8 days of age, body movement and hearing were examined for 6 and up to 17 weeks, respectively. Abnormal movements and deafness occurred only in rats treated during the preweaning period; within this period the greatest sensitivities for these abnormalities occurred from 2 to 11-17 and 5 to 11 days of age, respectively, indicating that the cochlea is more sensitive to streptomycin than the site (vestibular or central) responsible for the dyskinesias."],"offsets":[[76,671]]}],"entities":[{"id":"1590","type":"Disease","text":["neurotoxic"],"offsets":[[40,50]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"1591","type":"Chemical","text":["streptomycin"],"offsets":[[62,74]],"normalized":[{"db_name":"MESH","db_id":"D013307"}]},{"id":"1592","type":"Chemical","text":["Streptomycin"],"offsets":[[76,88]],"normalized":[{"db_name":"MESH","db_id":"D013307"}]},{"id":"1593","type":"Disease","text":["Abnormal movements"],"offsets":[[313,331]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"1594","type":"Disease","text":["deafness"],"offsets":[[336,344]],"normalized":[{"db_name":"MESH","db_id":"D003638"}]},{"id":"1595","type":"Chemical","text":["streptomycin"],"offsets":[[588,600]],"normalized":[{"db_name":"MESH","db_id":"D013307"}]},{"id":"1596","type":"Disease","text":["dyskinesias"],"offsets":[[659,670]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]}],"events":[],"coreferences":[],"relations":[{"id":"1597","type":"CID","arg1_id":"1591","arg2_id":"1593","normalized":[]},{"id":"1598","type":"CID","arg1_id":"1591","arg2_id":"1596","normalized":[]},{"id":"1599","type":"CID","arg1_id":"1592","arg2_id":"1593","normalized":[]},{"id":"1600","type":"CID","arg1_id":"1592","arg2_id":"1596","normalized":[]},{"id":"1601","type":"CID","arg1_id":"1595","arg2_id":"1593","normalized":[]},{"id":"1602","type":"CID","arg1_id":"1595","arg2_id":"1596","normalized":[]},{"id":"1603","type":"CID","arg1_id":"1591","arg2_id":"1594","normalized":[]},{"id":"1604","type":"CID","arg1_id":"1592","arg2_id":"1594","normalized":[]},{"id":"1605","type":"CID","arg1_id":"1595","arg2_id":"1594","normalized":[]}]}
{"id":"1606","document_id":"7834920","passages":[{"id":"1607","type":"title","text":["Crescentic fibrillary glomerulonephritis associated with intermittent rifampin therapy for pulmonary tuberculosis."],"offsets":[[0,114]]},{"id":"1608","type":"abstract","text":["This case study reveals an unusual finding of rapidly proliferative crescentic glomerulonephritis in a patient treated with rifampin who had no other identifiable causes for developing this disease. This patient underwent a 10-month regimen of rifampin and isoniazid for pulmonary tuberculosis and was discovered to have developed signs of severe renal failure five weeks after completion of therapy. Renal biopsy revealed severe glomerulonephritis with crescents, electron dense fibrillar deposits and moderate lymphocytic interstitial infiltrate. Other possible causes of rapidly progressive glomerulonephritis were investigated and ruled out. This report documents the unusual occurrence of rapidly progressive glomerulonephritis with crescents and fibrillar glomerulonephritis in a patient treated with rifampin."],"offsets":[[115,931]]}],"entities":[{"id":"1609","type":"Disease","text":["glomerulonephritis"],"offsets":[[22,40]],"normalized":[{"db_name":"MESH","db_id":"D005921"}]},{"id":"1610","type":"Chemical","text":["rifampin"],"offsets":[[70,78]],"normalized":[{"db_name":"MESH","db_id":"D012293"}]},{"id":"1611","type":"Disease","text":["pulmonary tuberculosis"],"offsets":[[91,113]],"normalized":[{"db_name":"MESH","db_id":"D014397"}]},{"id":"1612","type":"Disease","text":["glomerulonephritis"],"offsets":[[194,212]],"normalized":[{"db_name":"MESH","db_id":"D005921"}]},{"id":"1613","type":"Chemical","text":["rifampin"],"offsets":[[239,247]],"normalized":[{"db_name":"MESH","db_id":"D012293"}]},{"id":"1614","type":"Chemical","text":["rifampin"],"offsets":[[359,367]],"normalized":[{"db_name":"MESH","db_id":"D012293"}]},{"id":"1615","type":"Chemical","text":["isoniazid"],"offsets":[[372,381]],"normalized":[{"db_name":"MESH","db_id":"D007538"}]},{"id":"1616","type":"Disease","text":["pulmonary tuberculosis"],"offsets":[[386,408]],"normalized":[{"db_name":"MESH","db_id":"D014397"}]},{"id":"1617","type":"Disease","text":["renal failure"],"offsets":[[462,475]],"normalized":[{"db_name":"MESH","db_id":"D051437"}]},{"id":"1618","type":"Disease","text":["glomerulonephritis"],"offsets":[[545,563]],"normalized":[{"db_name":"MESH","db_id":"D005921"}]},{"id":"1619","type":"Disease","text":["glomerulonephritis"],"offsets":[[709,727]],"normalized":[{"db_name":"MESH","db_id":"D005921"}]},{"id":"1620","type":"Disease","text":["glomerulonephritis"],"offsets":[[829,847]],"normalized":[{"db_name":"MESH","db_id":"D005921"}]},{"id":"1621","type":"Disease","text":["glomerulonephritis"],"offsets":[[877,895]],"normalized":[{"db_name":"MESH","db_id":"D005921"}]},{"id":"1622","type":"Chemical","text":["rifampin"],"offsets":[[922,930]],"normalized":[{"db_name":"MESH","db_id":"D012293"}]}],"events":[],"coreferences":[],"relations":[{"id":"1623","type":"CID","arg1_id":"1610","arg2_id":"1609","normalized":[]},{"id":"1624","type":"CID","arg1_id":"1610","arg2_id":"1612","normalized":[]},{"id":"1625","type":"CID","arg1_id":"1610","arg2_id":"1618","normalized":[]},{"id":"1626","type":"CID","arg1_id":"1610","arg2_id":"1619","normalized":[]},{"id":"1627","type":"CID","arg1_id":"1610","arg2_id":"1620","normalized":[]},{"id":"1628","type":"CID","arg1_id":"1610","arg2_id":"1621","normalized":[]},{"id":"1629","type":"CID","arg1_id":"1613","arg2_id":"1609","normalized":[]},{"id":"1630","type":"CID","arg1_id":"1613","arg2_id":"1612","normalized":[]},{"id":"1631","type":"CID","arg1_id":"1613","arg2_id":"1618","normalized":[]},{"id":"1632","type":"CID","arg1_id":"1613","arg2_id":"1619","normalized":[]},{"id":"1633","type":"CID","arg1_id":"1613","arg2_id":"1620","normalized":[]},{"id":"1634","type":"CID","arg1_id":"1613","arg2_id":"1621","normalized":[]},{"id":"1635","type":"CID","arg1_id":"1614","arg2_id":"1609","normalized":[]},{"id":"1636","type":"CID","arg1_id":"1614","arg2_id":"1612","normalized":[]},{"id":"1637","type":"CID","arg1_id":"1614","arg2_id":"1618","normalized":[]},{"id":"1638","type":"CID","arg1_id":"1614","arg2_id":"1619","normalized":[]},{"id":"1639","type":"CID","arg1_id":"1614","arg2_id":"1620","normalized":[]},{"id":"1640","type":"CID","arg1_id":"1614","arg2_id":"1621","normalized":[]},{"id":"1641","type":"CID","arg1_id":"1622","arg2_id":"1609","normalized":[]},{"id":"1642","type":"CID","arg1_id":"1622","arg2_id":"1612","normalized":[]},{"id":"1643","type":"CID","arg1_id":"1622","arg2_id":"1618","normalized":[]},{"id":"1644","type":"CID","arg1_id":"1622","arg2_id":"1619","normalized":[]},{"id":"1645","type":"CID","arg1_id":"1622","arg2_id":"1620","normalized":[]},{"id":"1646","type":"CID","arg1_id":"1622","arg2_id":"1621","normalized":[]},{"id":"1647","type":"CID","arg1_id":"1610","arg2_id":"1617","normalized":[]},{"id":"1648","type":"CID","arg1_id":"1613","arg2_id":"1617","normalized":[]},{"id":"1649","type":"CID","arg1_id":"1614","arg2_id":"1617","normalized":[]},{"id":"1650","type":"CID","arg1_id":"1622","arg2_id":"1617","normalized":[]}]}
{"id":"1651","document_id":"7881871","passages":[{"id":"1652","type":"title","text":["Time course of lipid peroxidation in puromycin aminonucleoside-induced nephropathy."],"offsets":[[0,83]]},{"id":"1653","type":"abstract","text":["Reactive oxygen species have been implicated in the pathogenesis of acute puromycin aminonucleoside (PAN)-induced nephropathy, with antioxidants significantly reducing the proteinuria. The temporal relationship between lipid peroxidation in the kidney and proteinuria was examined in this study. Rats were treated with a single IV injection of puromycin aminonucleoside, (PAN, 7.5 mg\/kg) and 24 hour urine samples were obtained prior to sacrifice on days 3,5,7,10,17,27,41 (N = 5-10 per group). The kidneys were removed, flushed with ice cold TRIS buffer. Kidney cortices from each animal were used to prepare homogenates. Tissue lipid peroxidation was measured in whole homogenates as well as in lipid extracts from homogenates as thiobarbituric acid reactive substances. Proteinuria was evident at day 5, peaked at day 7 and persisted to day 27. Lipid peroxidation in homogenates was maximal at day 3 and declined rapidly to control levels by day 17. This study supports the role of lipid peroxidation in mediating the proteinuric injury in PAN nephropathy."],"offsets":[[84,1143]]}],"entities":[{"id":"1654","type":"Chemical","text":["puromycin aminonucleoside"],"offsets":[[37,62]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"1655","type":"Disease","text":["nephropathy"],"offsets":[[71,82]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"1656","type":"Chemical","text":["oxygen"],"offsets":[[93,99]],"normalized":[{"db_name":"MESH","db_id":"D010100"}]},{"id":"1657","type":"Chemical","text":["puromycin aminonucleoside"],"offsets":[[158,183]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"1658","type":"Chemical","text":["PAN"],"offsets":[[185,188]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"1659","type":"Disease","text":["nephropathy"],"offsets":[[198,209]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"1660","type":"Disease","text":["proteinuria"],"offsets":[[256,267]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]},{"id":"1661","type":"Disease","text":["proteinuria"],"offsets":[[340,351]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]},{"id":"1662","type":"Chemical","text":["puromycin aminonucleoside"],"offsets":[[428,453]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"1663","type":"Chemical","text":["PAN"],"offsets":[[456,459]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"1664","type":"Chemical","text":["thiobarbituric acid"],"offsets":[[816,835]],"normalized":[{"db_name":"MESH","db_id":"C029684"}]},{"id":"1665","type":"Disease","text":["Proteinuria"],"offsets":[[857,868]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]},{"id":"1666","type":"Disease","text":["proteinuric injury"],"offsets":[[1105,1123]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]},{"id":"1667","type":"Chemical","text":["PAN"],"offsets":[[1127,1130]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"1668","type":"Disease","text":["nephropathy"],"offsets":[[1131,1142]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]}],"events":[],"coreferences":[],"relations":[{"id":"1669","type":"CID","arg1_id":"1654","arg2_id":"1655","normalized":[]},{"id":"1670","type":"CID","arg1_id":"1654","arg2_id":"1659","normalized":[]},{"id":"1671","type":"CID","arg1_id":"1654","arg2_id":"1668","normalized":[]},{"id":"1672","type":"CID","arg1_id":"1657","arg2_id":"1655","normalized":[]},{"id":"1673","type":"CID","arg1_id":"1657","arg2_id":"1659","normalized":[]},{"id":"1674","type":"CID","arg1_id":"1657","arg2_id":"1668","normalized":[]},{"id":"1675","type":"CID","arg1_id":"1658","arg2_id":"1655","normalized":[]},{"id":"1676","type":"CID","arg1_id":"1658","arg2_id":"1659","normalized":[]},{"id":"1677","type":"CID","arg1_id":"1658","arg2_id":"1668","normalized":[]},{"id":"1678","type":"CID","arg1_id":"1662","arg2_id":"1655","normalized":[]},{"id":"1679","type":"CID","arg1_id":"1662","arg2_id":"1659","normalized":[]},{"id":"1680","type":"CID","arg1_id":"1662","arg2_id":"1668","normalized":[]},{"id":"1681","type":"CID","arg1_id":"1663","arg2_id":"1655","normalized":[]},{"id":"1682","type":"CID","arg1_id":"1663","arg2_id":"1659","normalized":[]},{"id":"1683","type":"CID","arg1_id":"1663","arg2_id":"1668","normalized":[]},{"id":"1684","type":"CID","arg1_id":"1667","arg2_id":"1655","normalized":[]},{"id":"1685","type":"CID","arg1_id":"1667","arg2_id":"1659","normalized":[]},{"id":"1686","type":"CID","arg1_id":"1667","arg2_id":"1668","normalized":[]},{"id":"1687","type":"CID","arg1_id":"1654","arg2_id":"1660","normalized":[]},{"id":"1688","type":"CID","arg1_id":"1654","arg2_id":"1661","normalized":[]},{"id":"1689","type":"CID","arg1_id":"1654","arg2_id":"1665","normalized":[]},{"id":"1690","type":"CID","arg1_id":"1654","arg2_id":"1666","normalized":[]},{"id":"1691","type":"CID","arg1_id":"1657","arg2_id":"1660","normalized":[]},{"id":"1692","type":"CID","arg1_id":"1657","arg2_id":"1661","normalized":[]},{"id":"1693","type":"CID","arg1_id":"1657","arg2_id":"1665","normalized":[]},{"id":"1694","type":"CID","arg1_id":"1657","arg2_id":"1666","normalized":[]},{"id":"1695","type":"CID","arg1_id":"1658","arg2_id":"1660","normalized":[]},{"id":"1696","type":"CID","arg1_id":"1658","arg2_id":"1661","normalized":[]},{"id":"1697","type":"CID","arg1_id":"1658","arg2_id":"1665","normalized":[]},{"id":"1698","type":"CID","arg1_id":"1658","arg2_id":"1666","normalized":[]},{"id":"1699","type":"CID","arg1_id":"1662","arg2_id":"1660","normalized":[]},{"id":"1700","type":"CID","arg1_id":"1662","arg2_id":"1661","normalized":[]},{"id":"1701","type":"CID","arg1_id":"1662","arg2_id":"1665","normalized":[]},{"id":"1702","type":"CID","arg1_id":"1662","arg2_id":"1666","normalized":[]},{"id":"1703","type":"CID","arg1_id":"1663","arg2_id":"1660","normalized":[]},{"id":"1704","type":"CID","arg1_id":"1663","arg2_id":"1661","normalized":[]},{"id":"1705","type":"CID","arg1_id":"1663","arg2_id":"1665","normalized":[]},{"id":"1706","type":"CID","arg1_id":"1663","arg2_id":"1666","normalized":[]},{"id":"1707","type":"CID","arg1_id":"1667","arg2_id":"1660","normalized":[]},{"id":"1708","type":"CID","arg1_id":"1667","arg2_id":"1661","normalized":[]},{"id":"1709","type":"CID","arg1_id":"1667","arg2_id":"1665","normalized":[]},{"id":"1710","type":"CID","arg1_id":"1667","arg2_id":"1666","normalized":[]}]}
{"id":"1711","document_id":"7930386","passages":[{"id":"1712","type":"title","text":["Clomipramine-induced sleep disturbance does not impair its prolactin-releasing action."],"offsets":[[0,86]]},{"id":"1713","type":"abstract","text":["The present study was undertaken to examine the role of sleep disturbance, induced by clomipramine administration, on the secretory rate of prolactin (PRL) in addition to the direct drug effect. Two groups of supine subjects were studied under placebo-controlled conditions, one during the night, when sleeping (n = 7) and the other at daytime, when awake (n = 6). Each subject received a single 50 mg dose of clomipramine given orally 2 hours before blood collection. Plasma PRL concentrations were analysed at 10 min intervals and underlying secretory rates calculated by a deconvolution procedure. For both experiments the drug intake led to significant increases in PRL secretion, acting preferentially on tonic secretion as pulse amplitude and frequency did not differ significantly from corresponding control values. During the night clomipramine ingestion altered the complete sleep architecture in that it suppressed REM sleep and the sleep cycles and induced increased wakefulness. As the relative increase in PRL secretion expressed as a percentage of the mean did not significantly differ between the night and day time studies (46 +\/- 19% vs 34 +\/- 10%), it can be concluded that the observed sleep disturbance did not interfere with the drug action per se. The presence of REM sleep was shown not to be a determining factor either for secretory pulse amplitude and frequency, as, for both, mean nocturnal values were similar with and without prior clomipramine ingestion."],"offsets":[[87,1571]]}],"entities":[{"id":"1714","type":"Chemical","text":["Clomipramine"],"offsets":[[0,12]],"normalized":[{"db_name":"MESH","db_id":"D002997"}]},{"id":"1715","type":"Disease","text":["sleep disturbance"],"offsets":[[21,38]],"normalized":[{"db_name":"MESH","db_id":"D012893"}]},{"id":"1716","type":"Disease","text":["sleep disturbance"],"offsets":[[143,160]],"normalized":[{"db_name":"MESH","db_id":"D012893"}]},{"id":"1717","type":"Chemical","text":["clomipramine"],"offsets":[[173,185]],"normalized":[{"db_name":"MESH","db_id":"D002997"}]},{"id":"1718","type":"Chemical","text":["clomipramine"],"offsets":[[497,509]],"normalized":[{"db_name":"MESH","db_id":"D002997"}]},{"id":"1719","type":"Chemical","text":["clomipramine"],"offsets":[[927,939]],"normalized":[{"db_name":"MESH","db_id":"D002997"}]},{"id":"1720","type":"Disease","text":["sleep disturbance"],"offsets":[[1292,1309]],"normalized":[{"db_name":"MESH","db_id":"D012893"}]},{"id":"1721","type":"Chemical","text":["clomipramine"],"offsets":[[1548,1560]],"normalized":[{"db_name":"MESH","db_id":"D002997"}]}],"events":[],"coreferences":[],"relations":[{"id":"1722","type":"CID","arg1_id":"1714","arg2_id":"1715","normalized":[]},{"id":"1723","type":"CID","arg1_id":"1714","arg2_id":"1716","normalized":[]},{"id":"1724","type":"CID","arg1_id":"1714","arg2_id":"1720","normalized":[]},{"id":"1725","type":"CID","arg1_id":"1717","arg2_id":"1715","normalized":[]},{"id":"1726","type":"CID","arg1_id":"1717","arg2_id":"1716","normalized":[]},{"id":"1727","type":"CID","arg1_id":"1717","arg2_id":"1720","normalized":[]},{"id":"1728","type":"CID","arg1_id":"1718","arg2_id":"1715","normalized":[]},{"id":"1729","type":"CID","arg1_id":"1718","arg2_id":"1716","normalized":[]},{"id":"1730","type":"CID","arg1_id":"1718","arg2_id":"1720","normalized":[]},{"id":"1731","type":"CID","arg1_id":"1719","arg2_id":"1715","normalized":[]},{"id":"1732","type":"CID","arg1_id":"1719","arg2_id":"1716","normalized":[]},{"id":"1733","type":"CID","arg1_id":"1719","arg2_id":"1720","normalized":[]},{"id":"1734","type":"CID","arg1_id":"1721","arg2_id":"1715","normalized":[]},{"id":"1735","type":"CID","arg1_id":"1721","arg2_id":"1716","normalized":[]},{"id":"1736","type":"CID","arg1_id":"1721","arg2_id":"1720","normalized":[]}]}
{"id":"1737","document_id":"7988234","passages":[{"id":"1738","type":"title","text":["Angioedema following the intravenous administration of metoprolol."],"offsets":[[0,66]]},{"id":"1739","type":"abstract","text":["A 72-year-old woman was admitted to the hospital with \"flash\" pulmonary edema, preceded by chest pain, requiring intubation. Her medical history included coronary artery disease with previous myocardial infarctions, hypertension, and diabetes mellitus. A history of angioedema secondary to lisinopril therapy was elicited. Current medications did not include angiotensin-converting enzyme inhibitors or beta-blockers. She had no previous beta-blocking drug exposure. During the first day of hospitalization (while intubated), intravenous metoprolol was given, resulting in severe angioedema. The angioedema resolved after therapy with intravenous steroids and diphenhydramine hydrochloride."],"offsets":[[67,757]]}],"entities":[{"id":"1740","type":"Disease","text":["Angioedema"],"offsets":[[0,10]],"normalized":[{"db_name":"MESH","db_id":"D000799"}]},{"id":"1741","type":"Chemical","text":["metoprolol"],"offsets":[[55,65]],"normalized":[{"db_name":"MESH","db_id":"D008790"}]},{"id":"1742","type":"Disease","text":["pulmonary edema"],"offsets":[[129,144]],"normalized":[{"db_name":"MESH","db_id":"D011654"}]},{"id":"1743","type":"Disease","text":["chest pain"],"offsets":[[158,168]],"normalized":[{"db_name":"MESH","db_id":"D002637"}]},{"id":"1744","type":"Disease","text":["coronary artery disease"],"offsets":[[221,244]],"normalized":[{"db_name":"MESH","db_id":"D003324"}]},{"id":"1745","type":"Disease","text":["myocardial infarctions"],"offsets":[[259,281]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"1746","type":"Disease","text":["hypertension"],"offsets":[[283,295]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"1747","type":"Disease","text":["diabetes mellitus"],"offsets":[[301,318]],"normalized":[{"db_name":"MESH","db_id":"D003920"}]},{"id":"1748","type":"Disease","text":["angioedema"],"offsets":[[333,343]],"normalized":[{"db_name":"MESH","db_id":"D000799"}]},{"id":"1749","type":"Chemical","text":["lisinopril"],"offsets":[[357,367]],"normalized":[{"db_name":"MESH","db_id":"D017706"}]},{"id":"1750","type":"Chemical","text":["angiotensin"],"offsets":[[426,437]],"normalized":[{"db_name":"MESH","db_id":"D000809"}]},{"id":"1751","type":"Chemical","text":["metoprolol"],"offsets":[[605,615]],"normalized":[{"db_name":"MESH","db_id":"D008790"}]},{"id":"1752","type":"Disease","text":["angioedema"],"offsets":[[647,657]],"normalized":[{"db_name":"MESH","db_id":"D000799"}]},{"id":"1753","type":"Disease","text":["angioedema"],"offsets":[[663,673]],"normalized":[{"db_name":"MESH","db_id":"D000799"}]},{"id":"1754","type":"Chemical","text":["steroids"],"offsets":[[714,722]],"normalized":[{"db_name":"MESH","db_id":"D013256"}]},{"id":"1755","type":"Chemical","text":["diphenhydramine"],"offsets":[[727,742]],"normalized":[{"db_name":"MESH","db_id":"D004155"}]}],"events":[],"coreferences":[],"relations":[{"id":"1756","type":"CID","arg1_id":"1741","arg2_id":"1740","normalized":[]},{"id":"1757","type":"CID","arg1_id":"1741","arg2_id":"1748","normalized":[]},{"id":"1758","type":"CID","arg1_id":"1741","arg2_id":"1752","normalized":[]},{"id":"1759","type":"CID","arg1_id":"1741","arg2_id":"1753","normalized":[]},{"id":"1760","type":"CID","arg1_id":"1751","arg2_id":"1740","normalized":[]},{"id":"1761","type":"CID","arg1_id":"1751","arg2_id":"1748","normalized":[]},{"id":"1762","type":"CID","arg1_id":"1751","arg2_id":"1752","normalized":[]},{"id":"1763","type":"CID","arg1_id":"1751","arg2_id":"1753","normalized":[]},{"id":"1764","type":"CID","arg1_id":"1749","arg2_id":"1740","normalized":[]},{"id":"1765","type":"CID","arg1_id":"1749","arg2_id":"1748","normalized":[]},{"id":"1766","type":"CID","arg1_id":"1749","arg2_id":"1752","normalized":[]},{"id":"1767","type":"CID","arg1_id":"1749","arg2_id":"1753","normalized":[]}]}
{"id":"1768","document_id":"8073369","passages":[{"id":"1769","type":"title","text":["Effect of coniine on the developing chick embryo."],"offsets":[[0,49]]},{"id":"1770","type":"abstract","text":["Coniine, an alkaloid from Conium maculatum (poison hemlock), has been shown to be teratogenic in livestock. The major teratogenic outcome is arthrogryposis, presumably due to nicotinic receptor blockade. However, coniine has failed to produce arthrogryposis in rats or mice and is only weakly teratogenic in rabbits. The purpose of this study was to evaluate and compare the effects of coniine and nicotine in the developing chick. Concentrations of coniine and nicotine sulfate were 0.015%, 0.03%, 0.075%, 0.15%, 0.75%, 1.5%, 3%, and 6% and 1%, 5%, and 10%, respectively. Both compounds caused deformations and lethality in a dose-dependent manner. All concentrations of nicotine sulfate caused some lethality but a no effect level for coniine lethality was 0.75%. The deformations caused by both coniine and nicotine sulfate were excessive flexion or extension of one or more toes. No histopathological alterations or differences in bone formation were seen in the limbs or toes of any chicks from any group; however, extensive cranial hemorrhage occurred in all nicotine sulfate-treated chicks. There was a statistically significant (P < or = 0.01) decrease in movement in coniine and nicotine sulfate treated chicks as determined by ultrasound. Control chicks were in motion an average of 33.67% of the time, while coniine-treated chicks were only moving 8.95% of a 5-min interval, and no movement was observed for nicotine sulfate treated chicks. In summary, the chick embryo provides a reliable and simple experimental animal model of coniine-induced arthrogryposis. Data from this model support a mechanism involving nicotinic receptor blockade with subsequent decreased fetal movement."],"offsets":[[50,1743]]}],"entities":[{"id":"1771","type":"Chemical","text":["coniine"],"offsets":[[10,17]],"normalized":[{"db_name":"MESH","db_id":"C007112"}]},{"id":"1772","type":"Chemical","text":["Coniine"],"offsets":[[50,57]],"normalized":[{"db_name":"MESH","db_id":"C007112"}]},{"id":"1773","type":"Disease","text":["arthrogryposis"],"offsets":[[191,205]],"normalized":[{"db_name":"MESH","db_id":"D001176"}]},{"id":"1774","type":"Chemical","text":["coniine"],"offsets":[[263,270]],"normalized":[{"db_name":"MESH","db_id":"C007112"}]},{"id":"1775","type":"Disease","text":["arthrogryposis"],"offsets":[[293,307]],"normalized":[{"db_name":"MESH","db_id":"D001176"}]},{"id":"1776","type":"Chemical","text":["coniine"],"offsets":[[436,443]],"normalized":[{"db_name":"MESH","db_id":"C007112"}]},{"id":"1777","type":"Chemical","text":["nicotine"],"offsets":[[448,456]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"1778","type":"Chemical","text":["coniine"],"offsets":[[500,507]],"normalized":[{"db_name":"MESH","db_id":"C007112"}]},{"id":"1779","type":"Chemical","text":["nicotine"],"offsets":[[512,520]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"1780","type":"Disease","text":["deformations"],"offsets":[[645,657]],"normalized":[{"db_name":"MESH","db_id":"D009140"}]},{"id":"1781","type":"Chemical","text":["nicotine"],"offsets":[[722,730]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"1782","type":"Chemical","text":["coniine"],"offsets":[[787,794]],"normalized":[{"db_name":"MESH","db_id":"C007112"}]},{"id":"1783","type":"Disease","text":["deformations"],"offsets":[[820,832]],"normalized":[{"db_name":"MESH","db_id":"D009140"}]},{"id":"1784","type":"Chemical","text":["coniine"],"offsets":[[848,855]],"normalized":[{"db_name":"MESH","db_id":"C007112"}]},{"id":"1785","type":"Chemical","text":["nicotine"],"offsets":[[860,868]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"1786","type":"Disease","text":["excessive flexion or extension of one or more toes"],"offsets":[[882,932]],"normalized":[{"db_name":"MESH","db_id":"D009140"}]},{"id":"1787","type":"Disease","text":["cranial hemorrhage"],"offsets":[[1080,1098]],"normalized":[{"db_name":"MESH","db_id":"D002543"}]},{"id":"1788","type":"Chemical","text":["nicotine"],"offsets":[[1115,1123]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"1789","type":"Chemical","text":["coniine"],"offsets":[[1226,1233]],"normalized":[{"db_name":"MESH","db_id":"C007112"}]},{"id":"1790","type":"Chemical","text":["nicotine"],"offsets":[[1238,1246]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"1791","type":"Chemical","text":["coniine"],"offsets":[[1369,1376]],"normalized":[{"db_name":"MESH","db_id":"C007112"}]},{"id":"1792","type":"Chemical","text":["nicotine"],"offsets":[[1469,1477]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"1793","type":"Chemical","text":["coniine"],"offsets":[[1591,1598]],"normalized":[{"db_name":"MESH","db_id":"C007112"}]},{"id":"1794","type":"Disease","text":["arthrogryposis"],"offsets":[[1607,1621]],"normalized":[{"db_name":"MESH","db_id":"D001176"}]}],"events":[],"coreferences":[],"relations":[{"id":"1795","type":"CID","arg1_id":"1777","arg2_id":"1773","normalized":[]},{"id":"1796","type":"CID","arg1_id":"1777","arg2_id":"1775","normalized":[]},{"id":"1797","type":"CID","arg1_id":"1777","arg2_id":"1794","normalized":[]},{"id":"1798","type":"CID","arg1_id":"1779","arg2_id":"1773","normalized":[]},{"id":"1799","type":"CID","arg1_id":"1779","arg2_id":"1775","normalized":[]},{"id":"1800","type":"CID","arg1_id":"1779","arg2_id":"1794","normalized":[]},{"id":"1801","type":"CID","arg1_id":"1781","arg2_id":"1773","normalized":[]},{"id":"1802","type":"CID","arg1_id":"1781","arg2_id":"1775","normalized":[]},{"id":"1803","type":"CID","arg1_id":"1781","arg2_id":"1794","normalized":[]},{"id":"1804","type":"CID","arg1_id":"1785","arg2_id":"1773","normalized":[]},{"id":"1805","type":"CID","arg1_id":"1785","arg2_id":"1775","normalized":[]},{"id":"1806","type":"CID","arg1_id":"1785","arg2_id":"1794","normalized":[]},{"id":"1807","type":"CID","arg1_id":"1788","arg2_id":"1773","normalized":[]},{"id":"1808","type":"CID","arg1_id":"1788","arg2_id":"1775","normalized":[]},{"id":"1809","type":"CID","arg1_id":"1788","arg2_id":"1794","normalized":[]},{"id":"1810","type":"CID","arg1_id":"1790","arg2_id":"1773","normalized":[]},{"id":"1811","type":"CID","arg1_id":"1790","arg2_id":"1775","normalized":[]},{"id":"1812","type":"CID","arg1_id":"1790","arg2_id":"1794","normalized":[]},{"id":"1813","type":"CID","arg1_id":"1792","arg2_id":"1773","normalized":[]},{"id":"1814","type":"CID","arg1_id":"1792","arg2_id":"1775","normalized":[]},{"id":"1815","type":"CID","arg1_id":"1792","arg2_id":"1794","normalized":[]},{"id":"1816","type":"CID","arg1_id":"1771","arg2_id":"1773","normalized":[]},{"id":"1817","type":"CID","arg1_id":"1771","arg2_id":"1775","normalized":[]},{"id":"1818","type":"CID","arg1_id":"1771","arg2_id":"1794","normalized":[]},{"id":"1819","type":"CID","arg1_id":"1772","arg2_id":"1773","normalized":[]},{"id":"1820","type":"CID","arg1_id":"1772","arg2_id":"1775","normalized":[]},{"id":"1821","type":"CID","arg1_id":"1772","arg2_id":"1794","normalized":[]},{"id":"1822","type":"CID","arg1_id":"1774","arg2_id":"1773","normalized":[]},{"id":"1823","type":"CID","arg1_id":"1774","arg2_id":"1775","normalized":[]},{"id":"1824","type":"CID","arg1_id":"1774","arg2_id":"1794","normalized":[]},{"id":"1825","type":"CID","arg1_id":"1776","arg2_id":"1773","normalized":[]},{"id":"1826","type":"CID","arg1_id":"1776","arg2_id":"1775","normalized":[]},{"id":"1827","type":"CID","arg1_id":"1776","arg2_id":"1794","normalized":[]},{"id":"1828","type":"CID","arg1_id":"1778","arg2_id":"1773","normalized":[]},{"id":"1829","type":"CID","arg1_id":"1778","arg2_id":"1775","normalized":[]},{"id":"1830","type":"CID","arg1_id":"1778","arg2_id":"1794","normalized":[]},{"id":"1831","type":"CID","arg1_id":"1782","arg2_id":"1773","normalized":[]},{"id":"1832","type":"CID","arg1_id":"1782","arg2_id":"1775","normalized":[]},{"id":"1833","type":"CID","arg1_id":"1782","arg2_id":"1794","normalized":[]},{"id":"1834","type":"CID","arg1_id":"1784","arg2_id":"1773","normalized":[]},{"id":"1835","type":"CID","arg1_id":"1784","arg2_id":"1775","normalized":[]},{"id":"1836","type":"CID","arg1_id":"1784","arg2_id":"1794","normalized":[]},{"id":"1837","type":"CID","arg1_id":"1789","arg2_id":"1773","normalized":[]},{"id":"1838","type":"CID","arg1_id":"1789","arg2_id":"1775","normalized":[]},{"id":"1839","type":"CID","arg1_id":"1789","arg2_id":"1794","normalized":[]},{"id":"1840","type":"CID","arg1_id":"1791","arg2_id":"1773","normalized":[]},{"id":"1841","type":"CID","arg1_id":"1791","arg2_id":"1775","normalized":[]},{"id":"1842","type":"CID","arg1_id":"1791","arg2_id":"1794","normalized":[]},{"id":"1843","type":"CID","arg1_id":"1793","arg2_id":"1773","normalized":[]},{"id":"1844","type":"CID","arg1_id":"1793","arg2_id":"1775","normalized":[]},{"id":"1845","type":"CID","arg1_id":"1793","arg2_id":"1794","normalized":[]},{"id":"1846","type":"CID","arg1_id":"1777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{"id":"1853","document_id":"8302922","passages":[{"id":"1854","type":"title","text":["Epidural blood flow during prostaglandin E1 or trimethaphan induced hypotension."],"offsets":[[0,80]]},{"id":"1855","type":"abstract","text":["To evaluate the effect of prostaglandin E1 (PGE1) or trimethaphan (TMP) induced hypotension on epidural blood flow (EBF) during spinal surgery, EBF was measured using the heat clearance method in 30 patients who underwent postero-lateral interbody fusion under isoflurane anaesthesia. An initial dose of 0.1 microgram.kg-1.min-1 of PGE1 (15 patients), or 10 micrograms.kg-1.min-1 of TMP (15 patients) was administered intravenously after the dural opening and the dose was adjusted to maintain the mean arterial blood pressure (MAP) at about 60 mmHg. The hypotensive drug was discontinued at the completion of the operative procedure. After starting PGE1 or TMP, MAP and rate pressure product (RPP) decreased significantly compared with preinfusion values (P < 0.01), and the degree of hypotension due to PGE1 remained constant until 60 min after its discontinuation. Heart rate (HR) did not change in either group. EBFF did not change during PGE1 infusion whereas in the TMP group, EBF decreased significantly at 30 and 60 min after the start of TMP (preinfusion: 45.9 +\/- 13.9 ml\/100g\/min. 30 min: 32.3 +\/- 9.9 ml\/100 g\/min (P < 0.05). 60 min: 30 +\/- 7.5 ml\/100 g\/min (P < 0.05)). These results suggest that PGE1 may be preferable to TMP for hypotensive anaesthesia in spinal surgery because TMP decreased EBF."],"offsets":[[81,1393]]}],"entities":[{"id":"1856","type":"Chemical","text":["prostaglandin E1"],"offsets":[[27,43]],"normalized":[{"db_name":"MESH","db_id":"D000527"}]},{"id":"1857","type":"Chemical","text":["trimethaphan"],"offsets":[[47,59]],"normalized":[{"db_name":"MESH","db_id":"D014294"}]},{"id":"1858","type":"Disease","text":["hypotension"],"offsets":[[68,79]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"1859","type":"Chemical","text":["prostaglandin 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{"id":"1964","document_id":"8410052","passages":[{"id":"1965","type":"title","text":["Immunohistochemical studies with antibodies to neurofilament proteins on axonal damage in experimental focal lesions in rat."],"offsets":[[0,124]]},{"id":"1966","type":"abstract","text":["Immunohistochemistry with monoclonal antibodies against neurofilament (NF) proteins of middle and high molecular weight class, NF-M and NF-H, was used to study axonal injury in the borderzone of focal lesions in rats. Focal injury in the cortex was produced by infusion of lactate at acid pH or by stab caused by needle insertion. Infarcts in substantia nigra pars reticulata were evoked by prolonged pilocarpine-induced status epilepticus. Immunohistochemical staining for NFs showed characteristic terminal clubs of axons in the borderzone of lesions. Differences in the labelling pattern occurred with different antibodies which apparently depended on molecular weight class of NFs and phosphorylation state. These immunohistochemical changes of NFs can serve as a marker for axonal damage in various experimental traumatic or ischemic lesions."],"offsets":[[125,972]]}],"entities":[{"id":"1967","type":"Disease","text":["axonal damage"],"offsets":[[73,86]],"normalized":[{"db_name":"MESH","db_id":"D001480"}]},{"id":"1968","type":"Disease","text":["axonal injury"],"offsets":[[285,298]],"normalized":[{"db_name":"MESH","db_id":"D001480"}]},{"id":"1969","type":"Disease","text":["injury in the cortex"],"offsets":[[349,369]],"normalized":[{"db_name":"MESH","db_id":"D001480"}]},{"id":"1970","type":"Chemical","text":["lactate"],"offsets":[[398,405]],"normalized":[{"db_name":"MESH","db_id":"D019344"}]},{"id":"1971","type":"Disease","text":["Infarcts in substantia nigra pars reticulata"],"offsets":[[456,500]],"normalized":[{"db_name":"MESH","db_id":"D002544"}]},{"id":"1972","type":"Chemical","text":["pilocarpine"],"offsets":[[526,537]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"1973","type":"Disease","text":["status epilepticus"],"offsets":[[546,564]],"normalized":[{"db_name":"MESH","db_id":"D013226"}]},{"id":"1974","type":"Disease","text":["axonal damage"],"offsets":[[904,917]],"normalized":[{"db_name":"MESH","db_id":"D001480"}]},{"id":"1975","type":"Disease","text":["traumatic"],"offsets":[[942,951]],"normalized":[{"db_name":"MESH","db_id":"D014947"}]}],"events":[],"coreferences":[],"relations":[{"id":"1976","type":"CID","arg1_id":"1972","arg2_id":"1973","normalized":[]},{"id":"1977","type":"CID","arg1_id":"1972","arg2_id":"1971","normalized":[]},{"id":"1978","type":"CID","arg1_id":"1972","arg2_id":"1967","normalized":[]},{"id":"1979","type":"CID","arg1_id":"1972","arg2_id":"1968","normalized":[]},{"id":"1980","type":"CID","arg1_id":"1972","arg2_id":"1969","normalized":[]},{"id":"1981","type":"CID","arg1_id":"1972","arg2_id":"1974","normalized":[]}]}
{"id":"1982","document_id":"8423889","passages":[{"id":"1983","type":"title","text":["Increase of Parkinson disability after fluoxetine medication."],"offsets":[[0,61]]},{"id":"1984","type":"abstract","text":["Depression is a major clinical feature of Parkinson's disease. We report the increased amount of motor disability in four patients with idiopathic Parkinson's disease after exposure to the antidepressant fluoxetine. The possibility of a clinically relevant dopamine-antagonistic capacity of fluoxetine in Parkinson's disease patients must be considered."],"offsets":[[62,415]]}],"entities":[{"id":"1985","type":"Disease","text":["Parkinson disability"],"offsets":[[12,32]],"normalized":[{"db_name":"MESH","db_id":"D009069"}]},{"id":"1986","type":"Chemical","text":["fluoxetine"],"offsets":[[39,49]],"normalized":[{"db_name":"MESH","db_id":"D005473"}]},{"id":"1987","type":"Disease","text":["Depression"],"offsets":[[62,72]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"1988","type":"Disease","text":["Parkinson's disease"],"offsets":[[104,123]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"1989","type":"Disease","text":["motor disability"],"offsets":[[159,175]],"normalized":[{"db_name":"MESH","db_id":"D009069"}]},{"id":"1990","type":"Disease","text":["idiopathic Parkinson's disease"],"offsets":[[198,228]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"1991","type":"Chemical","text":["antidepressant"],"offsets":[[251,265]],"normalized":[{"db_name":"MESH","db_id":"D000928"}]},{"id":"1992","type":"Chemical","text":["fluoxetine"],"offsets":[[266,276]],"normalized":[{"db_name":"MESH","db_id":"D005473"}]},{"id":"1993","type":"Chemical","text":["dopamine"],"offsets":[[319,327]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"1994","type":"Chemical","text":["fluoxetine"],"offsets":[[353,363]],"normalized":[{"db_name":"MESH","db_id":"D005473"}]},{"id":"1995","type":"Disease","text":["Parkinson's disease"],"offsets":[[367,386]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]}],"events":[],"coreferences":[],"relations":[{"id":"1996","type":"CID","arg1_id":"1986","arg2_id":"1985","normalized":[]},{"id":"1997","type":"CID","arg1_id":"1986","arg2_id":"1989","normalized":[]},{"id":"1998","type":"CID","arg1_id":"1992","arg2_id":"1985","normalized":[]},{"id":"1999","type":"CID","arg1_id":"1992","arg2_id":"1989","normalized":[]},{"id":"2000","type":"CID","arg1_id":"1994","arg2_id":"1985","normalized":[]},{"id":"2001","type":"CID","arg1_id":"1994","arg2_id":"1989","normalized":[]}]}
{"id":"2002","document_id":"8682684","passages":[{"id":"2003","type":"title","text":["Acetaminophen-induced hypotension."],"offsets":[[0,34]]},{"id":"2004","type":"abstract","text":["Through 30 years of widespread use, acetaminophen has been shown to be a remarkably safe medication in therapeutic dosages. The potential for acetaminophen to produce cardiovascular toxicities is very low. However, acetaminophen has been demonstrated to produce symptoms of anaphylaxis, including hypotension, in sensitive individuals. This article describes two critically ill patients in whom transient episodes of hypotension reproducibly developed after administration of acetaminophen. Other symptoms of allergic reactions were not clinically detectable. The hypotensive episodes were severe enough to require vasopressor administration. The reports illustrate the need for clinicians to consider acetaminophen in patients with hypotension of unknown origin."],"offsets":[[35,798]]}],"entities":[{"id":"2005","type":"Chemical","text":["Acetaminophen"],"offsets":[[0,13]],"normalized":[{"db_name":"MESH","db_id":"D000082"}]},{"id":"2006","type":"Disease","text":["hypotension"],"offsets":[[22,33]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"2007","type":"Chemical","text":["acetaminophen"],"offsets":[[71,84]],"normalized":[{"db_name":"MESH","db_id":"D000082"}]},{"id":"2008","type":"Chemical","text":["acetaminophen"],"offsets":[[177,190]],"normalized":[{"db_name":"MESH","db_id":"D000082"}]},{"id":"2009","type":"Disease","text":["cardiovascular toxicities"],"offsets":[[202,227]],"normalized":[{"db_name":"MESH","db_id":"D002318"}]},{"id":"2010","type":"Chemical","text":["acetaminophen"],"offsets":[[250,263]],"normalized":[{"db_name":"MESH","db_id":"D000082"}]},{"id":"2011","type":"Disease","text":["anaphylaxis"],"offsets":[[309,320]],"normalized":[{"db_name":"MESH","db_id":"D000707"}]},{"id":"2012","type":"Disease","text":["hypotension"],"offsets":[[332,343]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"2013","type":"Disease","text":["critically ill"],"offsets":[[398,412]],"normalized":[{"db_name":"MESH","db_id":"D016638"}]},{"id":"2014","type":"Disease","text":["hypotension"],"offsets":[[452,463]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"2015","type":"Chemical","text":["acetaminophen"],"offsets":[[511,524]],"normalized":[{"db_name":"MESH","db_id":"D000082"}]},{"id":"2016","type":"Disease","text":["allergic reactions"],"offsets":[[544,562]],"normalized":[{"db_name":"MESH","db_id":"D004342"}]},{"id":"2017","type":"Disease","text":["hypotensive"],"offsets":[[599,610]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"2018","type":"Chemical","text":["acetaminophen"],"offsets":[[737,750]],"normalized":[{"db_name":"MESH","db_id":"D000082"}]},{"id":"2019","type":"Disease","text":["hypotension"],"offsets":[[768,779]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]}],"events":[],"coreferences":[],"relations":[{"id":"2020","type":"CID","arg1_id":"2005","arg2_id":"2006","normalized":[]},{"id":"2021","type":"CID","arg1_id":"2005","arg2_id":"2012","normalized":[]},{"id":"2022","type":"CID","arg1_id":"2005","arg2_id":"2014","normalized":[]},{"id":"2023","type":"CID","arg1_id":"2005","arg2_id":"2017","normalized":[]},{"id":"2024","type":"CID","arg1_id":"2005","arg2_id":"2019","normalized":[]},{"id":"2025","type":"CID","arg1_id":"2007","arg2_id":"2006","normalized":[]},{"id":"2026","type":"CID","arg1_id":"2007","arg2_id":"2012","normalized":[]},{"id":"2027","type":"CID","arg1_id":"2007","arg2_id":"2014","normalized":[]},{"id":"2028","type":"CID","arg1_id":"2007","arg2_id":"2017","normalized":[]},{"id":"2029","type":"CID","arg1_id":"2007","arg2_id":"2019","normalized":[]},{"id":"2030","type":"CID","arg1_id":"2008","arg2_id":"2006","normalized":[]},{"id":"2031","type":"CID","arg1_id":"2008","arg2_id":"2012","normalized":[]},{"id":"2032","type":"CID","arg1_id":"2008","arg2_id":"2014","normalized":[]},{"id":"2033","type":"CID","arg1_id":"2008","arg2_id":"2017","normalized":[]},{"id":"2034","type":"CID","arg1_id":"2008","arg2_id":"2019","normalized":[]},{"id":"2035","type":"CID","arg1_id":"2010","arg2_id":"2006","normalized":[]},{"id":"2036","type":"CID","arg1_id":"2010","arg2_id":"2012","normalized":[]},{"id":"2037","type":"CID","arg1_id":"2010","arg2_id":"2014","normalized":[]},{"id":"2038","type":"CID","arg1_id":"2010","arg2_id":"2017","normalized":[]},{"id":"2039","type":"CID","arg1_id":"2010","arg2_id":"2019","normalized":[]},{"id":"2040","type":"CID","arg1_id":"2015","arg2_id":"2006","normalized":[]},{"id":"2041","type":"CID","arg1_id":"2015","arg2_id":"2012","normalized":[]},{"id":"2042","type":"CID","arg1_id":"2015","arg2_id":"2014","normalized":[]},{"id":"2043","type":"CID","arg1_id":"2015","arg2_id":"2017","normalized":[]},{"id":"2044","type":"CID","arg1_id":"2015","arg2_id":"2019","normalized":[]},{"id":"2045","type":"CID","arg1_id":"2018","arg2_id":"2006","normalized":[]},{"id":"2046","type":"CID","arg1_id":"2018","arg2_id":"2012","normalized":[]},{"id":"2047","type":"CID","arg1_id":"2018","arg2_id":"2014","normalized":[]},{"id":"2048","type":"CID","arg1_id":"2018","arg2_id":"2017","normalized":[]},{"id":"2049","type":"CID","arg1_id":"2018","arg2_id":"2019","normalized":[]}]}
{"id":"2050","document_id":"9625142","passages":[{"id":"2051","type":"title","text":["Acute hepatitis, autoimmune hemolytic anemia, and erythroblastocytopenia induced by ceftriaxone."],"offsets":[[0,96]]},{"id":"2052","type":"abstract","text":["An 80-yr-old man developed acute hepatitis shortly after ingesting oral ceftriaxone. Although the transaminases gradually returned to baseline after withholding the beta lactam antibiotic, there was a gradual increase in serum bilirubin and a decrease in hemoglobin concentration caused by an autoimmune hemolytic anemia and erythroblastocytopenia. These responded to systemic steroids and immunoglobulins. Despite the widespread use of these agents this triad of side effects has not previously been reported in connection with beta lactam antibiotics."],"offsets":[[97,650]]}],"entities":[{"id":"2053","type":"Disease","text":["hepatitis"],"offsets":[[6,15]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"2054","type":"Disease","text":["autoimmune hemolytic anemia"],"offsets":[[17,44]],"normalized":[{"db_name":"MESH","db_id":"D000744"}]},{"id":"2055","type":"Disease","text":["erythroblastocytopenia"],"offsets":[[50,72]],"normalized":[]},{"id":"2056","type":"Chemical","text":["ceftriaxone"],"offsets":[[84,95]],"normalized":[{"db_name":"MESH","db_id":"D002443"}]},{"id":"2057","type":"Disease","text":["hepatitis"],"offsets":[[130,139]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"2058","type":"Chemical","text":["ceftriaxone"],"offsets":[[169,180]],"normalized":[{"db_name":"MESH","db_id":"D002443"}]},{"id":"2059","type":"Chemical","text":["beta lactam"],"offsets":[[262,273]],"normalized":[{"db_name":"MESH","db_id":"D047090"}]},{"id":"2060","type":"Chemical","text":["bilirubin"],"offsets":[[324,333]],"normalized":[{"db_name":"MESH","db_id":"D001663"}]},{"id":"2061","type":"Disease","text":["autoimmune hemolytic anemia"],"offsets":[[390,417]],"normalized":[{"db_name":"MESH","db_id":"D000744"}]},{"id":"2062","type":"Disease","text":["erythroblastocytopenia"],"offsets":[[422,444]],"normalized":[]},{"id":"2063","type":"Chemical","text":["steroids"],"offsets":[[474,482]],"normalized":[{"db_name":"MESH","db_id":"D013256"}]},{"id":"2064","type":"Chemical","text":["beta lactam"],"offsets":[[626,637]],"normalized":[{"db_name":"MESH","db_id":"D047090"}]}],"events":[],"coreferences":[],"relations":[{"id":"2065","type":"CID","arg1_id":"2056","arg2_id":"2054","normalized":[]},{"id":"2066","type":"CID","arg1_id":"2056","arg2_id":"2061","normalized":[]},{"id":"2067","type":"CID","arg1_id":"2058","arg2_id":"2054","normalized":[]},{"id":"2068","type":"CID","arg1_id":"2058","arg2_id":"2061","normalized":[]},{"id":"2069","type":"CID","arg1_id":"2056","arg2_id":"2053","normalized":[]},{"id":"2070","type":"CID","arg1_id":"2056","arg2_id":"2057","normalized":[]},{"id":"2071","type":"CID","arg1_id":"2058","arg2_id":"2053","normalized":[]},{"id":"2072","type":"CID","arg1_id":"2058","arg2_id":"2057","normalized":[]}]}
{"id":"2073","document_id":"9766615","passages":[{"id":"2074","type":"title","text":["Adverse effects of the atypical antipsychotics. Collaborative Working Group on Clinical Trial Evaluations."],"offsets":[[0,106]]},{"id":"2075","type":"abstract","text":["Adverse effects of antipsychotics often lead to noncompliance. Thus, clinicians should address patients' concerns about adverse effects and attempt to choose medications that will improve their patients' quality of life as well as overall health. The side effect profiles of the atypical antipsychotics are more advantageous than those of the conventional neuroleptics. Conventional agents are associated with unwanted central nervous system effects, including extrapyramidal symptoms (EPS), tardive dyskinesia, sedation, and possible impairment of some cognitive measures, as well as cardiac effects, orthostatic hypotension, hepatic changes, anticholinergic side effects, sexual dysfunction, and weight gain. The newer atypical agents have a lower risk of EPS, but are associated in varying degrees with sedation, cardiovascular effects, anticholinergic effects, weight gain, sexual dysfunction, hepatic effects, lowered seizure threshold (primarily clozapine), and agranulocytosis (clozapine only). Since the incidence and severity of specific adverse effects differ among the various atypicals, the clinician should carefully consider which side effects are most likely to lead to the individual's dissatisfaction and noncompliance before choosing an antipsychotic for a particular patient."],"offsets":[[107,1401]]}],"entities":[{"id":"2076","type":"Disease","text":["extrapyramidal symptoms"],"offsets":[[568,591]],"normalized":[{"db_name":"MESH","db_id":"D001480"}]},{"id":"2077","type":"Disease","text":["EPS"],"offsets":[[593,596]],"normalized":[{"db_name":"MESH","db_id":"D001480"}]},{"id":"2078","type":"Disease","text":["tardive dyskinesia"],"offsets":[[599,617]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"2079","type":"Disease","text":["orthostatic hypotension"],"offsets":[[709,732]],"normalized":[{"db_name":"MESH","db_id":"D007024"}]},{"id":"2080","type":"Disease","text":["sexual dysfunction"],"offsets":[[781,799]],"normalized":[{"db_name":"MESH","db_id":"D012735"}]},{"id":"2081","type":"Disease","text":["weight gain"],"offsets":[[805,816]],"normalized":[{"db_name":"MESH","db_id":"D015430"}]},{"id":"2082","type":"Disease","text":["EPS"],"offsets":[[865,868]],"normalized":[{"db_name":"MESH","db_id":"D001480"}]},{"id":"2083","type":"Disease","text":["weight gain"],"offsets":[[972,983]],"normalized":[{"db_name":"MESH","db_id":"D015430"}]},{"id":"2084","type":"Disease","text":["sexual dysfunction"],"offsets":[[985,1003]],"normalized":[{"db_name":"MESH","db_id":"D012735"}]},{"id":"2085","type":"Disease","text":["seizure"],"offsets":[[1030,1037]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"2086","type":"Chemical","text":["clozapine"],"offsets":[[1059,1068]],"normalized":[{"db_name":"MESH","db_id":"D003024"}]},{"id":"2087","type":"Disease","text":["agranulocytosis"],"offsets":[[1075,1090]],"normalized":[{"db_name":"MESH","db_id":"D000380"}]},{"id":"2088","type":"Chemical","text":["clozapine"],"offsets":[[1092,1101]],"normalized":[{"db_name":"MESH","db_id":"D003024"}]}],"events":[],"coreferences":[],"relations":[{"id":"2089","type":"CID","arg1_id":"2086","arg2_id":"2087","normalized":[]},{"id":"2090","type":"CID","arg1_id":"2088","arg2_id":"2087","normalized":[]}]}
{"id":"2091","document_id":"10193204","passages":[{"id":"2092","type":"title","text":["Effects of tetrandrine and fangchinoline on experimental thrombosis in mice and human platelet aggregation."],"offsets":[[0,107]]},{"id":"2093","type":"abstract","text":["Tetrandrine (TET) and fangchinoline (FAN) are two naturally occurring analogues with a bisbenzylisoquinoline structure. The present study was undertaken to investigate the effects of TET and FAN on the experimental thrombosis induced by collagen plus epinephrine (EP) in mice, and platelet aggregation and blood coagulation in vitro. In the in vivo study, the administration (50 mg\/kg, i.p.) of TET and FAN in mice showed the inhibition of thrombosis by 55% and 35%, respectively, while acetylsalicylic acid (ASA, 50 mg\/kg, i.p.), a positive control, showed only 30% inhibition. In the vitro human platelet aggregations induced by the agonists used in tests, TET and FAN showed the inhibitions dose dependently. In addition, neither TET nor FAN showed any anticoagulation activities in the measurement of the activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT) using human-citrated plasma. These results suggest that antithrombosis of TET and FAN in mice may be mainly related to the antiplatelet aggregation activities."],"offsets":[[108,1167]]}],"entities":[{"id":"2094","type":"Chemical","text":["tetrandrine"],"offsets":[[11,22]],"normalized":[{"db_name":"MESH","db_id":"C009438"}]},{"id":"2095","type":"Chemical","text":["fangchinoline"],"offsets":[[27,40]],"normalized":[{"db_name":"MESH","db_id":"C060802"}]},{"id":"2096","type":"Disease","text":["thrombosis"],"offsets":[[57,67]],"normalized":[{"db_name":"MESH","db_id":"D013927"}]},{"id":"2097","type":"Disease","text":["platelet aggregation"],"offsets":[[86,106]],"normalized":[{"db_name":"MESH","db_id":"D001791"}]},{"id":"2098","type":"Chemical","text":["Tetrandrine"],"offsets":[[108,119]],"normalized":[{"db_name":"MESH","db_id":"C009438"}]},{"id":"2099","type":"Chemical","text":["TET"],"offsets":[[121,124]],"normalized":[{"db_name":"MESH","db_id":"C009438"}]},{"id":"2100","type":"Chemical","text":["fangchinoline"],"offsets":[[130,143]],"normalized":[{"db_name":"MESH","db_id":"C060802"}]},{"id":"2101","type":"Chemical","text":["FAN"],"offsets":[[145,148]],"normalized":[{"db_name":"MESH","db_id":"C060802"}]},{"id":"2102","type":"Chemical","text":["bisbenzylisoquinoline"],"offsets":[[195,216]],"normalized":[{"db_name":"MESH","db_id":"D044182"}]},{"id":"2103","type":"Chemical","text":["TET"],"offsets":[[291,294]],"normalized":[{"db_name":"MESH","db_id":"C009438"}]},{"id":"2104","type":"Chemical","text":["FAN"],"offsets":[[299,302]],"normalized":[{"db_name":"MESH","db_id":"C060802"}]},{"id":"2105","type":"Disease","text":["thrombosis"],"offsets":[[323,333]],"normalized":[{"db_name":"MESH","db_id":"D013927"}]},{"id":"2106","type":"Chemical","text":["epinephrine"],"offsets":[[359,370]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"2107","type":"Chemical","text":["EP"],"offsets":[[372,374]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"2108","type":"Disease","text":["platelet aggregation"],"offsets":[[389,409]],"normalized":[{"db_name":"MESH","db_id":"D001791"}]},{"id":"2109","type":"Disease","text":["blood coagulation"],"offsets":[[414,431]],"normalized":[{"db_name":"MESH","db_id":"D001778"}]},{"id":"2110","type":"Chemical","text":["TET"],"offsets":[[503,506]],"normalized":[{"db_name":"MESH","db_id":"C009438"}]},{"id":"2111","type":"Chemical","text":["FAN"],"offsets":[[511,514]],"normalized":[{"db_name":"MESH","db_id":"C060802"}]},{"id":"2112","type":"Disease","text":["thrombosis"],"offsets":[[548,558]],"normalized":[{"db_name":"MESH","db_id":"D013927"}]},{"id":"2113","type":"Chemical","text":["acetylsalicylic acid"],"offsets":[[595,615]],"normalized":[{"db_name":"MESH","db_id":"D001241"}]},{"id":"2114","type":"Chemical","text":["ASA"],"offsets":[[617,620]],"normalized":[{"db_name":"MESH","db_id":"D001241"}]},{"id":"2115","type":"Disease","text":["platelet aggregations"],"offsets":[[706,727]],"normalized":[{"db_name":"MESH","db_id":"D001791"}]},{"id":"2116","type":"Chemical","text":["TET"],"offsets":[[767,770]],"normalized":[{"db_name":"MESH","db_id":"C009438"}]},{"id":"2117","type":"Chemical","text":["FAN"],"offsets":[[775,778]],"normalized":[{"db_name":"MESH","db_id":"C060802"}]},{"id":"2118","type":"Chemical","text":["TET"],"offsets":[[841,844]],"normalized":[{"db_name":"MESH","db_id":"C009438"}]},{"id":"2119","type":"Chemical","text":["FAN"],"offsets":[[849,852]],"normalized":[{"db_name":"MESH","db_id":"C060802"}]},{"id":"2120","type":"Chemical","text":["TET"],"offsets":[[1082,1085]],"normalized":[{"db_name":"MESH","db_id":"C009438"}]},{"id":"2121","type":"Chemical","text":["FAN"],"offsets":[[1090,1093]],"normalized":[{"db_name":"MESH","db_id":"C060802"}]}],"events":[],"coreferences":[],"relations":[{"id":"2122","type":"CID","arg1_id":"2106","arg2_id":"2096","normalized":[]},{"id":"2123","type":"CID","arg1_id":"2106","arg2_id":"2105","normalized":[]},{"id":"2124","type":"CID","arg1_id":"2106","arg2_id":"2112","normalized":[]},{"id":"2125","type":"CID","arg1_id":"2107","arg2_id":"2096","normalized":[]},{"id":"2126","type":"CID","arg1_id":"2107","arg2_id":"2105","normalized":[]},{"id":"2127","type":"CID","arg1_id":"2107","arg2_id":"2112","normalized":[]}]}
{"id":"2128","document_id":"10526274","passages":[{"id":"2129","type":"title","text":["Gemcitabine plus vinorelbine in nonsmall cell lung carcinoma patients age 70 years or older or patients who cannot receive cisplatin. Oncopaz Cooperative Group."],"offsets":[[0,160]]},{"id":"2130","type":"abstract","text":["BACKGROUND: Although the prevalence of nonsmall cell lung carcinoma (NSCLC) is high among elderly patients, few data are available regarding the efficacy and toxicity of chemotherapy in this group of patients. Recent reports indicate that single agent therapy with vinorelbine (VNB) or gemcitabine (GEM) may obtain a response rate of 20-30% in elderly patients, with acceptable toxicity and improvement in symptoms and quality of life. In the current study the efficacy and toxicity of the combination of GEM and VNB in elderly patients with advanced NSCLC or those with some contraindication to receiving cisplatin were assessed. METHODS: Forty-nine patients with advanced NSCLC were included, 38 of whom were age >\/= 70 years and 11 were age < 70 years but who had some contraindication to receiving cisplatin. All patients were evaluable for response and toxicity. Treatment was comprised of VNB, 25 mg\/m(2), plus GEM, 1000 mg\/m(2), both on Days 1, 8, and 15 every 28 days. Patients received a minimum of three courses unless progressive disease was detected. RESULTS: One hundred sixty-five courses were administered, with a median of 3. 6 courses per patient. The overall response rate was 26% (95% confidence interval, 15-41%). Two patients attained a complete response (4%) and 11 patients (22%) achieved a partial response. Eastern Cooperative Oncology Group performance status improved in 35% of those patients with an initial value > 0, whereas relief of at least 1 symptom without worsening of other symptoms was noted in 27 patients (55%). The median time to progression was 16 weeks and the 1-year survival rate was 33%. Toxicity was mild. Six patients (12%) had World Health Organization Grade 3-4 neutropenia, 2 patients (4%) had Grade 3-4 thrombocytopenia, and 2 patients (4%) had Grade 3 neurotoxicity. Three patients with severe neutropenia (6%) died of sepsis. The median age of those patients developing Grade 3-4 neutropenia was significantly higher than that of the remaining patients (75 years vs. 72 years; P = 0.047). CONCLUSIONS: The combination of GEM and VNB is moderately active and well tolerated except in patients age >\/= 75 years. This age group had an increased risk of myelosuppression. Therefore the prophylactic use of granulocyte-colony stimulating factor should be considered with this treatment. New chemotherapy combinations with higher activity and lower toxicity are needed for elderly patients with advanced NSCLC."],"offsets":[[161,2619]]}],"entities":[{"id":"2131","type":"Chemical","text":["Gemcitabine"],"offsets":[[0,11]],"normalized":[{"db_name":"MESH","db_id":"C056507"}]},{"id":"2132","type":"Chemical","text":["vinorelbine"],"offsets":[[17,28]],"normalized":[{"db_name":"MESH","db_id":"C030852"}]},{"id":"2133","type":"Disease","text":["nonsmall cell lung carcinoma"],"offsets":[[32,60]],"normalized":[{"db_name":"MESH","db_id":"D002289"}]},{"id":"2134","type":"Chemical","text":["cisplatin"],"offsets":[[123,132]],"normalized":[{"db_name":"MESH","db_id":"D002945"}]},{"id":"2135","type":"Disease","text":["nonsmall cell lung 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{"id":"2225","document_id":"10669626","passages":[{"id":"2226","type":"title","text":["Warfarin-induced artery calcification is accelerated by growth and vitamin D."],"offsets":[[0,77]]},{"id":"2227","type":"abstract","text":["The present studies demonstrate that growth and vitamin D treatment enhance the extent of artery calcification in rats given sufficient doses of Warfarin to inhibit gamma-carboxylation of matrix Gla protein, a calcification inhibitor known to be expressed by smooth muscle cells and macrophages in the artery wall. The first series of experiments examined the influence of age and growth status on artery calcification in Warfarin-treated rats. Treatment for 2 weeks with Warfarin caused massive focal calcification of the artery media in 20-day-old rats and less extensive focal calcification in 42-day-old rats. In contrast, no artery calcification could be detected in 10-month-old adult rats even after 4 weeks of Warfarin treatment. To directly examine the importance of growth to Warfarin-induced artery calcification in animals of the same age, 20-day-old rats were fed for 2 weeks either an ad libitum diet or a 6-g\/d restricted diet that maintains weight but prevents growth. Concurrent treatment of both dietary groups with Warfarin produced massive focal calcification of the artery media in the ad libitum-fed rats but no detectable artery calcification in the restricted-diet, growth-inhibited group. Although the explanation for the association between artery calcification and growth status cannot be determined from the present study, there was a relationship between higher serum phosphate and susceptibility to artery calcification, with 30% higher levels of serum phosphate in young, ad libitum-fed rats compared with either of the groups that was resistant to Warfarin-induced artery calcification, ie, the 10-month-old rats and the restricted-diet, growth-inhibited young rats. This observation suggests that increased susceptibility to Warfarin-induced artery calcification could be related to higher serum phosphate levels. The second set of experiments examined the possible synergy between vitamin D and Warfarin in artery calcification. High doses of vitamin D are known to cause calcification of the artery media in as little as 3 to 4 days. High doses of the vitamin K antagonist Warfarin are also known to cause calcification of the artery media, but at treatment times of 2 weeks or longer yet not at 1 week. In the current study, we investigated the synergy between these 2 treatments and found that concurrent Warfarin administration dramatically increased the extent of calcification in the media of vitamin D-treated rats at 3 and 4 days. There was a close parallel between the effect of vitamin D dose on artery calcification and the effect of vitamin D dose on the elevation of serum calcium, which suggests that vitamin D may induce artery calcification through its effect on serum calcium. Because Warfarin treatment had no effect on the elevation in serum calcium produced by vitamin D, the synergy between Warfarin and vitamin D is probably best explained by the hypothesis that Warfarin inhibits the activity of matrix Gla protein as a calcification inhibitor. High levels of matrix Gla protein are found at sites of artery calcification in rats treated with vitamin D plus Warfarin, and chemical analysis showed that the protein that accumulated was indeed not gamma-carboxylated. These observations indicate that although the gamma-carboxyglutamate residues of matrix Gla protein are apparently required for its function as a calcification inhibitor, they are not required for its accumulation at calcification sites."],"offsets":[[78,3538]]}],"entities":[{"id":"2228","type":"Chemical","text":["Warfarin"],"offsets":[[0,8]],"normalized":[{"db_name":"MESH","db_id":"D014859"}]},{"id":"2229","type":"Disease","text":["artery calcification"],"offsets":[[17,37]],"normalized":[{"db_name":"MESH","db_id":"D061205"}]},{"id":"2230","type":"Chemical","text":["vitamin D"],"offsets":[[67,76]],"normalized":[{"db_name":"MESH","db_id":"D014807"}]},{"id":"2231","type":"Chemical","text":["vitamin D"],"offsets":[[126,135]],"normalized":[{"db_name":"MESH","db_id":"D014807"}]},{"id":"2232","type":"Disease","text":["artery 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{"id":"2576","document_id":"11379838","passages":[{"id":"2577","type":"title","text":["Antidepressant-induced mania in bipolar patients: identification of risk factors."],"offsets":[[0,81]]},{"id":"2578","type":"abstract","text":["BACKGROUND: Concerns about possible risks of switching to mania associated with antidepressants continue to interfere with the establishment of an optimal treatment paradigm for bipolar depression. METHOD: The response of 44 patients meeting DSM-IV criteria for bipolar disorder to naturalistic treatment was assessed for at least 6 weeks using the Montgomery-Asberg Depression Rating Scale and the Bech-Rafaelson Mania Rating Scale. Patients who experienced a manic or hypomanic switch were compared with those who did not on several variables including age, sex, diagnosis (DSM-IV bipolar I vs. bipolar II), number of previous manic episodes, type of antidepressant therapy used (electroconvulsive therapy vs. antidepressant drugs and, more particularly, selective serotonin reuptake inhibitors [SSRIs]), use and type of mood stabilizers (lithium vs. anticonvulsants), and temperament of the patient, assessed during a normothymic period using the hyperthymia component of the Semi-structured Affective Temperament Interview. RESULTS: Switches to hypomania or mania occurred in 27% of all patients (N = 12) (and in 24% of the subgroup of patients treated with SSRIs [8\/33]); 16% (N = 7) experienced manic episodes, and 11% (N = 5) experienced hypomanic episodes. Sex, age, diagnosis (bipolar I vs. bipolar II), and additional treatment did not affect the risk of switching. The incidence of mood switches seemed not to differ between patients receiving an anticonvulsant and those receiving no mood stabilizer. In contrast, mood switches were less frequent in patients receiving lithium (15%, 4\/26) than in patients not treated with lithium (44%, 8\/18; p = .04). The number of previous manic episodes did not affect the probability of switching, whereas a high score on the hyperthymia component of the Semistructured Affective Temperament Interview was associated with a greater risk of switching (p = .008). CONCLUSION: The frequency of mood switching associated with acute antidepressant therapy may be reduced by lithium treatment. Particular attention should be paid to patients with a hyperthymic temperament, who have a greater risk of mood switches."],"offsets":[[82,2241]]}],"entities":[{"id":"2579","type":"Chemical","text":["Antidepressant"],"offsets":[[0,14]],"normalized":[{"db_name":"MESH","db_id":"D000928"}]},{"id":"2580","type":"Disease","text":["mania"],"offsets":[[23,28]],"normalized":[{"db_name":"MESH","db_id":"D001714"}]},{"id":"2581","type":"Disease","text":["bipolar"],"offsets":[[32,39]],"normalized":[{"db_name":"MESH","db_id":"D001714"}]},{"id":"2582","type":"Disease","text":["mania"],"offsets":[[140,145]],"normalized":[{"db_name":"MESH","db_id":"D001714"}]},{"id":"2583","type":"Chemical","text":["antidepressants"],"offsets":[[162,177]],"normalized":[{"db_name":"MESH","db_id":"D000928"}]},{"id":"2584","type":"Disease","text":["bipolar depression"],"offsets":[[260,278]],"normalized":[{"db_name":"MESH","db_id":"D001714"}]},{"id":"2585","type":"Disease","text":["bipolar 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{"id":"2744","document_id":"11419773","passages":[{"id":"2745","type":"title","text":["Caffeine-induced cardiac arrhythmia: an unrecognised danger of healthfood products."],"offsets":[[0,83]]},{"id":"2746","type":"abstract","text":["We describe a 25-year-old woman with pre-existing mitral valve prolapse who developed intractable ventricular fibrillation after consuming a \"natural energy\" guarana health drink containing a high concentration of caffeine. This case highlights the need for adequate labelling and regulation of such products."],"offsets":[[84,393]]}],"entities":[{"id":"2747","type":"Chemical","text":["Caffeine"],"offsets":[[0,8]],"normalized":[{"db_name":"MESH","db_id":"D002110"}]},{"id":"2748","type":"Disease","text":["cardiac arrhythmia"],"offsets":[[17,35]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"2749","type":"Disease","text":["mitral valve prolapse"],"offsets":[[134,155]],"normalized":[{"db_name":"MESH","db_id":"D008945"}]},{"id":"2750","type":"Disease","text":["ventricular fibrillation"],"offsets":[[182,206]],"normalized":[{"db_name":"MESH","db_id":"D014693"}]},{"id":"2751","type":"Chemical","text":["caffeine"],"offsets":[[298,306]],"normalized":[{"db_name":"MESH","db_id":"D002110"}]}],"events":[],"coreferences":[],"relations":[{"id":"2752","type":"CID","arg1_id":"2747","arg2_id":"2750","normalized":[]},{"id":"2753","type":"CID","arg1_id":"2751","arg2_id":"2750","normalized":[]}]}
{"id":"2754","document_id":"11581460","passages":[{"id":"2755","type":"title","text":["Bladder retention of urine as a result of continuous intravenous infusion of fentanyl: 2 case reports."],"offsets":[[0,102]]},{"id":"2756","type":"abstract","text":["Sedation has been commonly used in the neonate to decrease the stress and pain from the noxious stimuli and invasive procedures in the neonatal intensive care unit, as well as to facilitate synchrony between ventilator and spontaneous breaths. Fentanyl, an opioid analgesic, is frequently used in the neonatal intensive care unit setting for these very purposes. Various reported side effects of fentanyl administration include chest wall rigidity, hypotension, respiratory depression, and bradycardia. Here, 2 cases of urinary bladder retention leading to renal pelvocalyceal dilatation mimicking hydronephrosis as a result of continuous infusion of fentanyl are reported."],"offsets":[[103,776]]}],"entities":[{"id":"2757","type":"Disease","text":["retention of urine"],"offsets":[[8,26]],"normalized":[{"db_name":"MESH","db_id":"D016055"}]},{"id":"2758","type":"Chemical","text":["fentanyl"],"offsets":[[77,85]],"normalized":[{"db_name":"MESH","db_id":"D005283"}]},{"id":"2759","type":"Disease","text":["pain"],"offsets":[[177,181]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"2760","type":"Chemical","text":["Fentanyl"],"offsets":[[347,355]],"normalized":[{"db_name":"MESH","db_id":"D005283"}]},{"id":"2761","type":"Chemical","text":["fentanyl"],"offsets":[[499,507]],"normalized":[{"db_name":"MESH","db_id":"D005283"}]},{"id":"2762","type":"Disease","text":["chest wall rigidity"],"offsets":[[531,550]],"normalized":[{"db_name":"MESH","db_id":"D009127"}]},{"id":"2763","type":"Disease","text":["hypotension"],"offsets":[[552,563]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"2764","type":"Disease","text":["respiratory depression"],"offsets":[[565,587]],"normalized":[{"db_name":"MESH","db_id":"D012131"}]},{"id":"2765","type":"Disease","text":["bradycardia"],"offsets":[[593,604]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"2766","type":"Disease","text":["urinary bladder retention"],"offsets":[[623,648]],"normalized":[{"db_name":"MESH","db_id":"D001745"}]},{"id":"2767","type":"Disease","text":["hydronephrosis"],"offsets":[[701,715]],"normalized":[{"db_name":"MESH","db_id":"D006869"}]},{"id":"2768","type":"Chemical","text":["fentanyl"],"offsets":[[754,762]],"normalized":[{"db_name":"MESH","db_id":"D005283"}]}],"events":[],"coreferences":[],"relations":[{"id":"2769","type":"CID","arg1_id":"2758","arg2_id":"2764","normalized":[]},{"id":"2770","type":"CID","arg1_id":"2760","arg2_id":"2764","normalized":[]},{"id":"2771","type":"CID","arg1_id":"2761","arg2_id":"2764","normalized":[]},{"id":"2772","type":"CID","arg1_id":"2768","arg2_id":"2764","normalized":[]},{"id":"2773","type":"CID","arg1_id":"2758","arg2_id":"2763","normalized":[]},{"id":"2774","type":"CID","arg1_id":"2760","arg2_id":"2763","normalized":[]},{"id":"2775","type":"CID","arg1_id":"2761","arg2_id":"2763","normalized":[]},{"id":"2776","type":"CID","arg1_id":"2768","arg2_id":"2763","normalized":[]},{"id":"2777","type":"CID","arg1_id":"2758","arg2_id":"2766","normalized":[]},{"id":"2778","type":"CID","arg1_id":"2760","arg2_id":"2766","normalized":[]},{"id":"2779","type":"CID","arg1_id":"2761","arg2_id":"2766","normalized":[]},{"id":"2780","type":"CID","arg1_id":"2768","arg2_id":"2766","normalized":[]},{"id":"2781","type":"CID","arg1_id":"2758","arg2_id":"2765","normalized":[]},{"id":"2782","type":"CID","arg1_id":"2760","arg2_id":"2765","normalized":[]},{"id":"2783","type":"CID","arg1_id":"2761","arg2_id":"2765","normalized":[]},{"id":"2784","type":"CID","arg1_id":"2768","arg2_id":"2765","normalized":[]},{"id":"2785","type":"CID","arg1_id":"2758","arg2_id":"2757","normalized":[]},{"id":"2786","type":"CID","arg1_id":"2760","arg2_id":"2757","normalized":[]},{"id":"2787","type":"CID","arg1_id":"2761","arg2_id":"2757","normalized":[]},{"id":"2788","type":"CID","arg1_id":"2768","arg2_id":"2757","normalized":[]}]}
{"id":"2789","document_id":"11706060","passages":[{"id":"2790","type":"title","text":["Combined antiretroviral therapy causes cardiomyopathy and elevates plasma lactate in transgenic AIDS mice."],"offsets":[[0,106]]},{"id":"2791","type":"abstract","text":["Highly active antiretroviral therapy (HAART) is implicated in cardiomyopathy (CM) and in elevated plasma lactate (LA) in AIDS through mechanisms of mitochondrial dysfunction. To determine mitochondrial events from HAART in vivo, 8-week-old hemizygous transgenic AIDS mice (NL4-3Delta gag\/pol; TG) and wild-type FVB\/n littermates were treated with the HAART combination of zidovudine, lamivudine, and indinavir or vehicle control for 10 days or 35 days. At termination of the experiments, mice underwent echocardiography, quantitation of abundance of molecular markers of CM (ventricular mRNA encoding atrial natriuretic factor [ANF] and sarcoplasmic calcium ATPase [SERCA2]), and determination of plasma LA. Myocardial histologic features were analyzed semiquantitatively and results were confirmed by transmission electron microscopy. After 35 days in the TG + HAART cohort, left ventricular mass increased 160% by echocardiography. Molecularly, ANF mRNA increased 250% and SERCA2 mRNA decreased 57%. Biochemically, LA was elevated (8.5 +\/- 2.0 mM). Pathologically, granular cytoplasmic changes were found in cardiac myocytes, indicating enlarged, damaged mitochondria. Findings were confirmed ultrastructurally. No changes were found in other cohorts. After 10 days, only ANF was elevated, and only in the TG + HAART cohort. Results show that cumulative HAART caused mitochondrial CM with elevated LA in AIDS transgenic mice."],"offsets":[[107,1534]]}],"entities":[{"id":"2792","type":"Disease","text":["cardiomyopathy"],"offsets":[[39,53]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"2793","type":"Chemical","text":["lactate"],"offsets":[[74,81]],"normalized":[{"db_name":"MESH","db_id":"D019344"}]},{"id":"2794","type":"Disease","text":["AIDS"],"offsets":[[96,100]],"normalized":[{"db_name":"MESH","db_id":"D000163"}]},{"id":"2795","type":"Disease","text":["cardiomyopathy"],"offsets":[[169,183]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"2796","type":"Disease","text":["CM"],"offsets":[[185,187]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"2797","type":"Chemical","text":["lactate"],"offsets":[[212,219]],"normalized":[{"db_name":"MESH","db_id":"D019344"}]},{"id":"2798","type":"Chemical","text":["LA"],"offsets":[[221,223]],"normalized":[{"db_name":"MESH","db_id":"D019344"}]},{"id":"2799","type":"Disease","text":["AIDS"],"offsets":[[228,232]],"normalized":[{"db_name":"MESH","db_id":"D000163"}]},{"id":"2800","type":"Disease","text":["mitochondrial dysfunction"],"offsets":[[255,280]],"normalized":[{"db_name":"MESH","db_id":"D028361"}]},{"id":"2801","type":"Disease","text":["AIDS"],"offsets":[[369,373]],"normalized":[{"db_name":"MESH","db_id":"D000163"}]},{"id":"2802","type":"Chemical","text":["zidovudine"],"offsets":[[479,489]],"normalized":[{"db_name":"MESH","db_id":"D015215"}]},{"id":"2803","type":"Chemical","text":["lamivudine"],"offsets":[[491,501]],"normalized":[{"db_name":"MESH","db_id":"D019259"}]},{"id":"2804","type":"Chemical","text":["indinavir"],"offsets":[[507,516]],"normalized":[{"db_name":"MESH","db_id":"D019469"}]},{"id":"2805","type":"Disease","text":["CM"],"offsets":[[678,680]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"2806","type":"Chemical","text":["calcium"],"offsets":[[757,764]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"2807","type":"Chemical","text":["LA"],"offsets":[[811,813]],"normalized":[{"db_name":"MESH","db_id":"D019344"}]},{"id":"2808","type":"Chemical","text":["LA"],"offsets":[[1124,1126]],"normalized":[{"db_name":"MESH","db_id":"D019344"}]},{"id":"2809","type":"Disease","text":["CM"],"offsets":[[1490,1492]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"2810","type":"Chemical","text":["LA"],"offsets":[[1507,1509]],"normalized":[{"db_name":"MESH","db_id":"D019344"}]},{"id":"2811","type":"Disease","text":["AIDS"],"offsets":[[1513,1517]],"normalized":[{"db_name":"MESH","db_id":"D000163"}]}],"events":[],"coreferences":[],"relations":[{"id":"2812","type":"CID","arg1_id":"2804","arg2_id":"2792","normalized":[]},{"id":"2813","type":"CID","arg1_id":"2804","arg2_id":"2795","normalized":[]},{"id":"2814","type":"CID","arg1_id":"2804","arg2_id":"2796","normalized":[]},{"id":"2815","type":"CID","arg1_id":"2804","arg2_id":"2805","normalized":[]},{"id":"2816","type":"CID","arg1_id":"2804","arg2_id":"2809","normalized":[]},{"id":"2817","type":"CID","arg1_id":"2803","arg2_id":"2792","normalized":[]},{"id":"2818","type":"CID","arg1_id":"2803","arg2_id":"2795","normalized":[]},{"id":"2819","type":"CID","arg1_id":"2803","arg2_id":"2796","normalized":[]},{"id":"2820","type":"CID","arg1_id":"2803","arg2_id":"2805","normalized":[]},{"id":"2821","type":"CID","arg1_id":"2803","arg2_id":"2809","normalized":[]},{"id":"2822","type":"CID","arg1_id":"2802","arg2_id":"2792","normalized":[]},{"id":"2823","type":"CID","arg1_id":"2802","arg2_id":"2795","normalized":[]},{"id":"2824","type":"CID","arg1_id":"2802","arg2_id":"2796","normalized":[]},{"id":"2825","type":"CID","arg1_id":"2802","arg2_id":"2805","normalized":[]},{"id":"2826","type":"CID","arg1_id":"2802","arg2_id":"2809","normalized":[]}]}
{"id":"2827","document_id":"11752354","passages":[{"id":"2828","type":"title","text":["Oral contraceptives and the risk of myocardial infarction."],"offsets":[[0,58]]},{"id":"2829","type":"abstract","text":["BACKGROUND: An association between the use of oral contraceptives and the risk of myocardial infarction has been found in some, but not all, studies. We investigated this association, according to the type of progestagen included in third-generation (i.e., desogestrel or gestodene) and second-generation (i.e., levonorgestrel) oral contraceptives, the dose of estrogen, and the presence or absence of prothrombotic mutations METHODS: In a nationwide, population-based, case-control study, we identified and enrolled 248 women 18 through 49 years of age who had had a first myocardial infarction between 1990 and 1995 and 925 control women who had not had a myocardial infarction and who were matched for age, calendar year of the index event, and area of residence. Subjects supplied information on oral-contraceptive use and major cardiovascular risk factors. An analysis for factor V Leiden and the G20210A mutation in the prothrombin gene was conducted in 217 patients and 763 controls RESULTS: The odds ratio for myocardial infarction among women who used any type of combined oral contraceptive, as compared with nonusers, was 2.0 (95 percent confidence interval, 1.5 to 2.8). The adjusted odds ratio was 2.5 (95 percent confidence interval, 1.5 to 4.1) among women who used second-generation oral contraceptives and 1.3 (95 percent confidence interval, 0.7 to 2.5) among those who used third-generation oral contraceptives. Among women who used oral contraceptives, the odds ratio was 2.1 (95 percent confidence interval, 1.5 to 3.0) for those without a prothrombotic mutation and 1.9 (95 percent confidence interval, 0.6 to 5.5) for those with a mutation CONCLUSIONS: The risk of myocardial infarction was increased among women who used second-generation oral contraceptives. The results with respect to the use of third-generation oral contraceptives were inconclusive but suggested that the risk was lower than the risk associated with second-generation oral contraceptives. The risk of myocardial infarction was similar among women who used oral contraceptives whether or not they had a prothrombotic mutation."],"offsets":[[59,2180]]}],"entities":[{"id":"2830","type":"Chemical","text":["Oral contraceptives"],"offsets":[[0,19]],"normalized":[{"db_name":"MESH","db_id":"D003276"}]},{"id":"2831","type":"Disease","text":["myocardial infarction"],"offsets":[[36,57]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"2832","type":"Chemical","text":["oral contraceptives"],"offsets":[[105,124]],"normalized":[{"db_name":"MESH","db_id":"D003276"}]},{"id":"2833","type":"Disease","text":["myocardial infarction"],"offsets":[[141,162]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"2834","type":"Chemical","text":["progestagen"],"offsets":[[268,279]],"normalized":[{"db_name":"MESH","db_id":"D011372"}]},{"id":"2835","type":"Chemical","text":["desogestrel"],"offsets":[[316,327]],"normalized":[{"db_name":"MESH","db_id":"D017135"}]},{"id":"2836","type":"Chemical","text":["gestodene"],"offsets":[[331,340]],"normalized":[{"db_name":"MESH","db_id":"C033273"}]},{"id":"2837","type":"Chemical","text":["levonorgestrel"],"offsets":[[371,385]],"normalized":[{"db_name":"MESH","db_id":"D016912"}]},{"id":"2838","type":"Chemical","text":["oral contraceptives"],"offsets":[[387,406]],"normalized":[{"db_name":"MESH","db_id":"D003276"}]},{"id":"2839","type":"Chemical","text":["estrogen"],"offsets":[[420,428]],"normalized":[{"db_name":"MESH","db_id":"D004967"}]},{"id":"2840","type":"Disease","text":["myocardial infarction"],"offsets":[[633,654]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"2841","type":"Disease","text":["myocardial infarction"],"offsets":[[717,738]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"2842","type":"Chemical","text":["oral-contraceptive"],"offsets":[[859,877]],"normalized":[{"db_name":"MESH","db_id":"D003276"}]},{"id":"2843","type":"Disease","text":["myocardial infarction"],"offsets":[[1077,1098]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"2844","type":"Chemical","text":["oral contraceptive"],"offsets":[[1141,1159]],"normalized":[{"db_name":"MESH","db_id":"D003276"}]},{"id":"2845","type":"Chemical","text":["oral contraceptives"],"offsets":[[1358,1377]],"normalized":[{"db_name":"MESH","db_id":"D003276"}]},{"id":"2846","type":"Chemical","text":["oral contraceptives"],"offsets":[[1469,1488]],"normalized":[{"db_name":"MESH","db_id":"D003276"}]},{"id":"2847","type":"Chemical","text":["oral 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{"id":"2938","document_id":"12369736","passages":[{"id":"2939","type":"title","text":["Effects of 5-HT1B receptor ligands microinjected into the accumbal shell or core on the cocaine-induced locomotor hyperactivity in rats."],"offsets":[[0,136]]},{"id":"2940","type":"abstract","text":["The present study was designed to examine the effect of 5-HT1B receptor ligands microinjected into the subregions of the nucleus accumbens (the shell and the core) on the locomotor hyperactivity induced by cocaine in rats. Male Wistar rats were implanted bilaterally with cannulae into the accumbens shell or core, and then were locally injected with GR 55562 (an antagonist of 5-HT1B receptors) or CP 93129 (an agonist of 5-HT1B receptors). Given alone to any accumbal subregion, GR 55562 (0.1-10 microg\/side) or CP 93129 (0.1-10 microg\/side) did not change basal locomotor activity. Systemic cocaine (10 mg\/kg) significantly increased the locomotor activity of rats. GR 55562 (0.1-10 microg\/side), administered intra-accumbens shell prior to cocaine, dose-dependently attenuated the psychostimulant-induced locomotor hyperactivity. Such attenuation was not found in animals which had been injected with GR 55562 into the accumbens core. When injected into the accumbens shell (but not the core) before cocaine, CP 93129 (0.1-10 microg\/side) enhanced the locomotor response to cocaine; the maximum effect being observed after 10 microg\/side of the agonist. The later enhancement was attenuated after intra-accumbens shell treatment with GR 55562 (1 microg\/side). Our findings indicate that cocaine induced hyperlocomotion is modified by 5-HT1B receptor ligands microinjected into the accumbens shell, but not core, this modification consisting in inhibitory and facilitatory effects of the 5-HT1B receptor antagonist (GR 55562) and agonist (CP 93129), respectively. In other words, the present results suggest that the accumbal shell 5-HT1B receptors play a permissive role in the behavioural response to the psychostimulant."],"offsets":[[137,1863]]}],"entities":[{"id":"2941","type":"Chemical","text":["cocaine"],"offsets":[[88,95]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"2942","type":"Disease","text":["locomotor hyperactivity"],"offsets":[[104,127]],"normalized":[{"db_name":"MESH","db_id":"D009069"}]},{"id":"2943","type":"Disease","text":["locomotor hyperactivity"],"offsets":[[308,331]],"normalized":[{"db_name":"MESH","db_id":"D009069"}]},{"id":"2944","type":"Chemical","text":["cocaine"],"offsets":[[343,350]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"2945","type":"Chemical","text":["GR 55562"],"offsets":[[488,496]],"normalized":[{"db_name":"MESH","db_id":"C103477"}]},{"id":"2946","type":"Chemical","text":["CP 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{"id":"3006","document_id":"12639165","passages":[{"id":"3007","type":"title","text":["Ticlopidine-induced cholestatic hepatitis."],"offsets":[[0,42]]},{"id":"3008","type":"abstract","text":["OBJECTIVE: To report 2 cases of ticlopidine-induced cholestatic hepatitis, investigate its mechanism, and compare the observed main characteristics with those of the published cases. CASE SUMMARIES: Two patients developed prolonged cholestatic hepatitis after receiving ticlopidine following percutaneous coronary angioplasty, with complete remission during the follow-up period. T-cell stimulation by therapeutic concentration of ticlopidine was demonstrated in vitro in the patients, but not in healthy controls. DISCUSSION: Cholestatic hepatitis is a rare complication of the antiplatelet agent ticlopidine; several cases have been reported but few in the English literature. Our patients developed jaundice following treatment with ticlopidine and showed the clinical and laboratory characteristics of cholestatic hepatitis, which resolved after discontinuation of the drug. Hepatitis may develop weeks after discontinuation of the drug and may run a prolonged course, but complete remission was observed in all reported cases. An objective causality assessment revealed that the adverse drug event was probably related to the use of ticlopidine. The mechanisms of this ticlopidine-induced cholestasis are unclear. Immune mechanisms may be involved in the drug's hepatotoxicity, as suggested by the T-cell stimulation study reported here. CONCLUSIONS: Cholestatic hepatitis is a rare adverse effect of ticlopidine that may be immune mediated. Patients receiving the drug should be monitored with liver function tests along with complete blood cell counts. This complication will be observed even less often in the future as ticlopidine is being replaced by the newer antiplatelet agent clopidogrel."],"offsets":[[43,1745]]}],"entities":[{"id":"3009","type":"Chemical","text":["Ticlopidine"],"offsets":[[0,11]],"normalized":[{"db_name":"MESH","db_id":"D013988"}]},{"id":"3010","type":"Disease","text":["cholestatic hepatitis"],"offsets":[[20,41]],"normalized":[{"db_name":"MESH","db_id":"D002779"},{"db_name":"MESH","db_id":"D056486"}]},{"id":"3011","type":"Disease","text":["cholestatic"],"offsets":[[20,31]],"normalized":[{"db_name":"MESH","db_id":"D002779"}]},{"id":"3012","type":"Disease","text":["hepatitis"],"offsets":[[32,41]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"3013","type":"Chemical","text":["ticlopidine"],"offsets":[[75,86]],"normalized":[{"db_name":"MESH","db_id":"D013988"}]},{"id":"3014","type":"Disease","text":["cholestatic 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{"id":"3322","document_id":"12653683","passages":[{"id":"3323","type":"title","text":["Epithelial sodium channel (ENaC) subunit mRNA and protein expression in rats with puromycin aminonucleoside-induced nephrotic syndrome."],"offsets":[[0,135]]},{"id":"3324","type":"abstract","text":["In experimental nephrotic syndrome, urinary sodium excretion is decreased during the early phase of the disease. The molecular mechanism(s) leading to salt retention has not been completely elucidated. The rate-limiting constituent of collecting duct sodium transport is the epithelial sodium channel (ENaC). We examined the abundance of ENaC subunit mRNAs and proteins in puromycin aminonucleoside (PAN)-induced nephrotic syndrome. The time courses of urinary sodium excretion, plasma aldosterone concentration and proteinuria were studied in male Sprague-Dawley rats treated with a single dose of either PAN or vehicle. The relative amounts of alphaENaC, betaENaC and gammaENaC mRNAs were determined in kidneys from these rats by real-time quantitative TaqMan PCR, and the amounts of proteins by Western blot. The kinetics of urinary sodium excretion and the appearance of proteinuria were comparable with those reported previously. Sodium retention occurred on days 2, 3 and 6 after PAN injection. A significant up-regulation of alphaENaC and betaENaC mRNA abundance on days 1 and 2 preceded sodium retention on days 2 and 3. Conversely, down-regulation of alphaENaC, betaENaC and gammaENaC mRNA expression on day 3 occurred in the presence of high aldosterone concentrations, and was followed by a return of sodium excretion to control values. The amounts of alphaENaC, betaENaC and gammaENaC proteins were not increased during PAN-induced sodium retention. In conclusion, ENaC mRNA expression, especially alphaENaC, is increased in the very early phase of the experimental model of PAN-induced nephrotic syndrome in rats, but appears to escape from the regulation by aldosterone after day 3."],"offsets":[[136,1832]]}],"entities":[{"id":"3325","type":"Chemical","text":["sodium"],"offsets":[[11,17]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"3326","type":"Chemical","text":["puromycin aminonucleoside"],"offsets":[[82,107]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"3327","type":"Disease","text":["nephrotic syndrome"],"offsets":[[116,134]],"normalized":[{"db_name":"MESH","db_id":"D009404"}]},{"id":"3328","type":"Disease","text":["nephrotic 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{"id":"3393","document_id":"14659530","passages":[{"id":"3394","type":"title","text":["NO-induced migraine attack: strong increase in plasma calcitonin gene-related peptide (CGRP) concentration and negative correlation with platelet serotonin release."],"offsets":[[0,164]]},{"id":"3395","type":"abstract","text":["The aim of the present study was to investigate changes in the plasma calcitonin gene-related peptide (CGRP) concentration and platelet serotonin (5-hydroxytriptamine, 5-HT) content during the immediate headache and the delayed genuine migraine attack provoked by nitroglycerin. Fifteen female migraineurs (without aura) and eight controls participated in the study. Sublingual nitroglycerin (0.5 mg) was administered. Blood was collected from the antecubital vein four times: 60 min before and after the nitroglycerin application, and 60 and 120 min after the beginning of the migraine attack (mean 344 and 404 min; 12 subjects). In those subjects who had no migraine attack (11 subjects) a similar time schedule was used. Plasma CGRP concentration increased significantly (P<0.01) during the migraine attack and returned to baseline after the cessation of the migraine. In addition, both change and peak, showed significant positive correlations with migraine headache intensity (P<0.001). However, plasma CGRP concentrations failed to change during immediate headache and in the subjects with no migraine attack. Basal CGRP concentration was significantly higher and platelet 5-HT content tended to be lower in subjects who experienced a migraine attack. Platelet serotonin content decreased significantly (P<0.01) after nitroglycerin in subjects with no migraine attack but no consistent change was observed in patients with migraine attack. In conclusion, the fact that plasma CGRP concentration correlates with the timing and severity of a migraine headache suggests a direct relationship between CGRP and migraine. In contrast, serotonin release from platelets does not provoke migraine, it may even counteract the headache and the concomitant CGRP release in this model."],"offsets":[[165,1943]]}],"entities":[{"id":"3396","type":"Chemical","text":["NO"],"offsets":[[0,2]],"normalized":[{"db_name":"MESH","db_id":"D009569"}]},{"id":"3397","type":"Disease","text":["migraine"],"offsets":[[11,19]],"normalized":[{"db_name":"MESH","db_id":"D008881"}]},{"id":"3398","type":"Chemical","text":["calcitonin gene-related peptide"],"offsets":[[54,85]],"normalized":[{"db_name":"MESH","db_id":"D015740"}]},{"id":"3399","type":"Chemical","text":["CGRP"],"offsets":[[87,91]],"normalized":[{"db_name":"MESH","db_id":"D015740"}]},{"id":"3400","type":"Chemical","text":["serotonin"],"offsets":[[146,155]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"3401","type":"Chemical","text":["calcitonin gene-related peptide"],"offsets":[[235,266]],"normalized":[{"db_name":"MESH","db_id":"D015740"}]},{"id":"3402","type":"Chemical","text":["CGRP"],"offsets":[[268,272]],"normalized":[{"db_name":"MESH","db_id":"D015740"}]},{"id":"3403","type":"Chemical","text":["serotonin"],"offsets":[[301,310]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"3404","type":"Chemical","text":["5-hydroxytriptamine"],"offsets":[[312,331]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"3405","type":"Chemical","text":["5-HT"],"offsets":[[333,337]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"3406","type":"Disease","text":["headache"],"offsets":[[368,376]],"normalized":[{"db_name":"MESH","db_id":"D006261"}]},{"id":"3407","type":"Disease","text":["migraine"],"offsets":[[401,409]],"normalized":[{"db_name":"MESH","db_id":"D008881"}]},{"id":"3408","type":"Chemical","text":["nitroglycerin"],"offsets":[[429,442]],"normalized":[{"db_name":"MESH","db_id":"D005996"}]},{"id":"3409","type":"Disease","text":["migraineurs (without aura)"],"offsets":[[459,485]],"normalized":[{"db_name":"MESH","db_id":"D020326"}]},{"id":"3410","type":"Chemical","text":["nitroglycerin"],"offsets":[[543,556]],"normalized":[{"db_name":"MESH","db_id":"D005996"}]},{"id":"3411","type":"Chemical","text":["nitroglycerin"],"offsets":[[670,683]],"normalized":[{"db_name":"MESH","db_id":"D005996"}]},{"id":"3412","type":"Disease","text":["migraine"],"offsets":[[743,751]],"normalized":[{"db_name":"MESH","db_id":"D008881"}]},{"id":"3413","type":"Disease","text":["migraine"],"offsets":[[825,833]],"normalized":[{"db_name":"MESH","db_id":"D008881"}]},{"id":"3414","type":"Chemical","text":["CGRP"],"offsets":[[896,900]],"normalized":[{"db_name":"MESH","db_id":"D015740"}]},{"id":"3415","type":"Disease","text":["migraine"],"offsets":[[959,967]],"normalized":[{"db_name":"MESH","db_id":"D008881"}]},{"id":"3416","type":"Disease","text":["migraine"],"offsets":[[1027,1035]],"normalized":[{"db_name":"MESH","db_id":"D008881"}]},{"id":"3417","type":"Disease","text":["migraine"],"offsets":[[1118,1126]],"normalized":[{"db_name":"MESH","db_id":"D008881"}]},{"id":"3418","type":"Disease","text":["headache"],"offsets":[[1127,1135]],"normalized":[{"db_name":"MESH","db_id":"D006261"}]},{"id":"3419","type":"Chemical","text":["CGRP"],"offsets":[[1173,1177]],"normalized":[{"db_name":"MESH","db_id":"D015740"}]},{"id":"3420","type":"Disease","text":["headache"],"offsets":[[1227,1235]],"normalized":[{"db_name":"MESH","db_id":"D006261"}]},{"id":"3421","type":"Disease","text":["migraine"],"offsets":[[1264,1272]],"normalized":[{"db_name":"MESH","db_id":"D008881"}]},{"id":"3422","type":"Chemical","text":["CGRP"],"offsets":[[1287,1291]],"normalized":[{"db_name":"MESH","db_id":"D015740"}]},{"id":"3423","type":"Chemical","text":["5-HT"],"offsets":[[1344,1348]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"3424","type":"Disease","text":["migraine"],"offsets":[[1406,1414]],"normalized":[{"db_name":"MESH","db_id":"D008881"}]},{"id":"3425","type":"Chemical","text":["serotonin"],"offsets":[[1432,1441]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"3426","type":"Chemical","text":["nitroglycerin"],"offsets":[[1489,1502]],"normalized":[{"db_name":"MESH","db_id":"D005996"}]},{"id":"3427","type":"Disease","text":["migraine"],"offsets":[[1523,1531]],"normalized":[{"db_name":"MESH","db_id":"D008881"}]},{"id":"3428","type":"Disease","text":["migraine"],"offsets":[[1594,1602]],"normalized":[{"db_name":"MESH","db_id":"D008881"}]},{"id":"3429","type":"Chemical","text":["CGRP"],"offsets":[[1647,1651]],"normalized":[{"db_name":"MESH","db_id":"D015740"}]},{"id":"3430","type":"Disease","text":["migraine"],"offsets":[[1711,1719]],"normalized":[{"db_name":"MESH","db_id":"D008881"}]},{"id":"3431","type":"Disease","text":["headache"],"offsets":[[1720,1728]],"normalized":[{"db_name":"MESH","db_id":"D006261"}]},{"id":"3432","type":"Chemical","text":["CGRP"],"offsets":[[1768,1772]],"normalized":[{"db_name":"MESH","db_id":"D015740"}]},{"id":"3433","type":"Disease","text":["migraine"],"offsets":[[1777,1785]],"normalized":[{"db_name":"MESH","db_id":"D008881"}]},{"id":"3434","type":"Chemical","text":["serotonin"],"offsets":[[1800,1809]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"3435","type":"Disease","text":["migraine"],"offsets":[[1850,1858]],"normalized":[{"db_name":"MESH","db_id":"D008881"}]},{"id":"3436","type":"Disease","text":["headache"],"offsets":[[1887,1895]],"normalized":[{"db_name":"MESH","db_id":"D006261"}]},{"id":"3437","type":"Chemical","text":["CGRP"],"offsets":[[1916,1920]],"normalized":[{"db_name":"MESH","db_id":"D015740"}]}],"events":[],"coreferences":[],"relations":[{"id":"3438","type":"CID","arg1_id":"3408","arg2_id":"3409","normalized":[]},{"id":"3439","type":"CID","arg1_id":"3410","arg2_id":"3409","normalized":[]},{"id":"3440","type":"CID","arg1_id":"3411","arg2_id":"3409","normalized":[]},{"id":"3441","type":"CID","arg1_id":"3426","arg2_id":"3409","normalized":[]},{"id":"3442","type":"CID","arg1_id":"3396","arg2_id":"3409","normalized":[]}]}
{"id":"3443","document_id":"15804801","passages":[{"id":"3444","type":"title","text":["Coronary aneurysm after implantation of a paclitaxel-eluting stent."],"offsets":[[0,67]]},{"id":"3445","type":"abstract","text":["Formation of coronary aneurysm is a rare complication of stenting with bare metal stents, but based on experimental studies drug-eluting stents may induce toxic effects on the vessel wall with incomplete stent apposition, aneurysm formation and with the potential of stent thrombosis or vessel rupture. We present a 43-year-old man who developed a coronary aneurysm in the right coronary artery 6 months after receiving a paclitaxel-eluting stent. The patient was asymptomatic and the aneurysm was detected in a routine control. Angiography and intracoronary ultrasound demonstrated lack of contact between stent and vessel wall in a 15-mm long segment with maximal aneurysm diameter of 6.0 mm. The patient was successfully treated with a graft stent."],"offsets":[[68,819]]}],"entities":[{"id":"3446","type":"Disease","text":["Coronary aneurysm"],"offsets":[[0,17]],"normalized":[{"db_name":"MESH","db_id":"D003323"}]},{"id":"3447","type":"Chemical","text":["paclitaxel"],"offsets":[[42,52]],"normalized":[{"db_name":"MESH","db_id":"D017239"}]},{"id":"3448","type":"Disease","text":["coronary aneurysm"],"offsets":[[81,98]],"normalized":[{"db_name":"MESH","db_id":"D003323"}]},{"id":"3449","type":"Disease","text":["aneurysm"],"offsets":[[290,298]],"normalized":[{"db_name":"MESH","db_id":"D000783"}]},{"id":"3450","type":"Disease","text":["thrombosis"],"offsets":[[341,351]],"normalized":[{"db_name":"MESH","db_id":"D013927"}]},{"id":"3451","type":"Disease","text":["vessel rupture"],"offsets":[[355,369]],"normalized":[]},{"id":"3452","type":"Disease","text":["coronary aneurysm"],"offsets":[[416,433]],"normalized":[{"db_name":"MESH","db_id":"D003323"}]},{"id":"3453","type":"Chemical","text":["paclitaxel"],"offsets":[[490,500]],"normalized":[{"db_name":"MESH","db_id":"D017239"}]},{"id":"3454","type":"Disease","text":["aneurysm"],"offsets":[[553,561]],"normalized":[{"db_name":"MESH","db_id":"D000783"}]},{"id":"3455","type":"Disease","text":["aneurysm"],"offsets":[[734,742]],"normalized":[{"db_name":"MESH","db_id":"D000783"}]}],"events":[],"coreferences":[],"relations":[{"id":"3456","type":"CID","arg1_id":"3447","arg2_id":"3446","normalized":[]},{"id":"3457","type":"CID","arg1_id":"3447","arg2_id":"3448","normalized":[]},{"id":"3458","type":"CID","arg1_id":"3447","arg2_id":"3452","normalized":[]},{"id":"3459","type":"CID","arg1_id":"3453","arg2_id":"3446","normalized":[]},{"id":"3460","type":"CID","arg1_id":"3453","arg2_id":"3448","normalized":[]},{"id":"3461","type":"CID","arg1_id":"3453","arg2_id":"3452","normalized":[]}]}
{"id":"3462","document_id":"16160878","passages":[{"id":"3463","type":"title","text":["Behavioral effects of urotensin-II centrally administered in mice."],"offsets":[[0,66]]},{"id":"3464","type":"abstract","text":["Urotensin-II (U-II) receptors are widely distributed in the central nervous system. Intracerebroventricular (i.c.v.) injection of U-II causes hypertension and bradycardia and stimulates prolactin and thyrotropin secretion. However, the behavioral effects of centrally administered U-II have received little attention. In the present study, we tested the effects of i.c.v. injections of U-II on behavioral, metabolic, and endocrine responses in mice. Administration of graded doses of U-II (1-10,000 ng\/mouse) provoked: (1) a dose-dependent reduction in the number of head dips in the hole-board test; (2) a dose-dependent reduction in the number of entries in the white chamber in the black-and-white compartment test, and in the number of entries in the central platform and open arms in the plus-maze test; and (3) a dose-dependent increase in the duration of immobility in the forced-swimming test and tail suspension test. Intracerebroventricular injection of U-II also caused an increase in: food intake at doses of 100 and 1,000 ng\/mouse, water intake at doses of 100-10,000 ng\/mouse, and horizontal locomotion activity at a dose of 10,000 ng\/mouse. Whatever was the dose, the central administration of U-II had no effect on body temperature, nociception, apomorphine-induced penile erection and climbing behavior, and stress-induced plasma corticosterone level. Taken together, the present study demonstrates that the central injection of U-II at doses of 1-10,000 ng\/mouse induces anxiogenic- and depressant-like effects in mouse. These data suggest that U-II may be involved in some aspects of psychiatric disorders."],"offsets":[[67,1692]]}],"entities":[{"id":"3465","type":"Chemical","text":["urotensin-II"],"offsets":[[22,34]],"normalized":[{"db_name":"MESH","db_id":"D014579"}]},{"id":"3466","type":"Chemical","text":["Urotensin-II"],"offsets":[[67,79]],"normalized":[{"db_name":"MESH","db_id":"D014579"}]},{"id":"3467","type":"Chemical","text":["U-II"],"offsets":[[81,85]],"normalized":[{"db_name":"MESH","db_id":"D014579"}]},{"id":"3468","type":"Chemical","text":["U-II"],"offsets":[[197,201]],"normalized":[{"db_name":"MESH","db_id":"D014579"}]},{"id":"3469","type":"Disease","text":["hypertension"],"offsets":[[209,221]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"3470","type":"Disease","text":["bradycardia"],"offsets":[[226,237]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"3471","type":"Chemical","text":["U-II"],"offsets":[[348,352]],"normalized":[{"db_name":"MESH","db_id":"D014579"}]},{"id":"3472","type":"Chemical","text":["U-II"],"offsets":[[453,457]],"normalized":[{"db_name":"MESH","db_id":"D014579"}]},{"id":"3473","type":"Chemical","text":["U-II"],"offsets":[[551,555]],"normalized":[{"db_name":"MESH","db_id":"D014579"}]},{"id":"3474","type":"Chemical","text":["U-II"],"offsets":[[1031,1035]],"normalized":[{"db_name":"MESH","db_id":"D014579"}]},{"id":"3475","type":"Chemical","text":["U-II"],"offsets":[[1276,1280]],"normalized":[{"db_name":"MESH","db_id":"D014579"}]},{"id":"3476","type":"Chemical","text":["apomorphine"],"offsets":[[1329,1340]],"normalized":[{"db_name":"MESH","db_id":"D001058"}]},{"id":"3477","type":"Disease","text":["penile erection"],"offsets":[[1349,1364]],"normalized":[{"db_name":"MESH","db_id":"D010409"}]},{"id":"3478","type":"Chemical","text":["corticosterone"],"offsets":[[1414,1428]],"normalized":[{"db_name":"MESH","db_id":"D003345"}]},{"id":"3479","type":"Chemical","text":["U-II"],"offsets":[[1513,1517]],"normalized":[{"db_name":"MESH","db_id":"D014579"}]},{"id":"3480","type":"Chemical","text":["U-II"],"offsets":[[1630,1634]],"normalized":[{"db_name":"MESH","db_id":"D014579"}]},{"id":"3481","type":"Disease","text":["psychiatric disorders"],"offsets":[[1670,1691]],"normalized":[{"db_name":"MESH","db_id":"D001523"}]}],"events":[],"coreferences":[],"relations":[{"id":"3482","type":"CID","arg1_id":"3476","arg2_id":"3477","normalized":[]}]}
{"id":"3483","document_id":"16274958","passages":[{"id":"3484","type":"title","text":["Recurrent dysphonia and acitretin."],"offsets":[[0,34]]},{"id":"3485","type":"abstract","text":["We report the case of a woman complaining of dysphonia while she was treated by acitretin. Her symptoms totally regressed after drug withdrawal and reappeared when acitretin was reintroduced. To our knowledge, this is the first case of acitretin-induced dysphonia. This effect may be related to the pharmacological effect of this drug on mucous membranes."],"offsets":[[35,390]]}],"entities":[{"id":"3486","type":"Disease","text":["dysphonia"],"offsets":[[10,19]],"normalized":[{"db_name":"MESH","db_id":"D055154"}]},{"id":"3487","type":"Chemical","text":["acitretin"],"offsets":[[24,33]],"normalized":[{"db_name":"MESH","db_id":"D017255"}]},{"id":"3488","type":"Disease","text":["dysphonia"],"offsets":[[80,89]],"normalized":[{"db_name":"MESH","db_id":"D055154"}]},{"id":"3489","type":"Chemical","text":["acitretin"],"offsets":[[115,124]],"normalized":[{"db_name":"MESH","db_id":"D017255"}]},{"id":"3490","type":"Chemical","text":["acitretin"],"offsets":[[199,208]],"normalized":[{"db_name":"MESH","db_id":"D017255"}]},{"id":"3491","type":"Chemical","text":["acitretin"],"offsets":[[271,280]],"normalized":[{"db_name":"MESH","db_id":"D017255"}]},{"id":"3492","type":"Disease","text":["dysphonia"],"offsets":[[289,298]],"normalized":[{"db_name":"MESH","db_id":"D055154"}]}],"events":[],"coreferences":[],"relations":[{"id":"3493","type":"CID","arg1_id":"3487","arg2_id":"3486","normalized":[]},{"id":"3494","type":"CID","arg1_id":"3487","arg2_id":"3488","normalized":[]},{"id":"3495","type":"CID","arg1_id":"3487","arg2_id":"3492","normalized":[]},{"id":"3496","type":"CID","arg1_id":"3489","arg2_id":"3486","normalized":[]},{"id":"3497","type":"CID","arg1_id":"3489","arg2_id":"3488","normalized":[]},{"id":"3498","type":"CID","arg1_id":"3489","arg2_id":"3492","normalized":[]},{"id":"3499","type":"CID","arg1_id":"3490","arg2_id":"3486","normalized":[]},{"id":"3500","type":"CID","arg1_id":"3490","arg2_id":"3488","normalized":[]},{"id":"3501","type":"CID","arg1_id":"3490","arg2_id":"3492","normalized":[]},{"id":"3502","type":"CID","arg1_id":"3491","arg2_id":"3486","normalized":[]},{"id":"3503","type":"CID","arg1_id":"3491","arg2_id":"3488","normalized":[]},{"id":"3504","type":"CID","arg1_id":"3491","arg2_id":"3492","normalized":[]}]}
{"id":"3505","document_id":"16330766","passages":[{"id":"3506","type":"title","text":["Pharmacological modulation of pain-related brain activity during normal and central sensitization states in humans."],"offsets":[[0,115]]},{"id":"3507","type":"abstract","text":["Abnormal processing of somatosensory inputs in the central nervous system (central sensitization) is the mechanism accounting for the enhanced pain sensitivity in the skin surrounding tissue injury (secondary hyperalgesia). Secondary hyperalgesia shares clinical characteristics with neurogenic hyperalgesia in patients with neuropathic pain. Abnormal brain responses to somatosensory stimuli have been found in patients with hyperalgesia as well as in normal subjects during experimental central sensitization. The aim of this study was to assess the effects of gabapentin, a drug effective in neuropathic pain patients, on brain processing of nociceptive information in normal and central sensitization states. Using functional magnetic resonance imaging (fMRI) in normal volunteers, we studied the gabapentin-induced modulation of brain activity in response to nociceptive mechanical stimulation of normal skin and capsaicin-induced secondary hyperalgesia. The dose of gabapentin was 1,800 mg per os, in a single administration. We found that (i) gabapentin reduced the activations in the bilateral operculoinsular cortex, independently of the presence of central sensitization; (ii) gabapentin reduced the activation in the brainstem, only during central sensitization; (iii) gabapentin suppressed stimulus-induced deactivations, only during central sensitization; this effect was more robust than the effect on brain activation. The observed drug-induced effects were not due to changes in the baseline fMRI signal. These findings indicate that gabapentin has a measurable antinociceptive effect and a stronger antihyperalgesic effect most evident in the brain areas undergoing deactivation, thus supporting the concept that gabapentin is more effective in modulating nociceptive transmission when central sensitization is present."],"offsets":[[116,1952]]}],"entities":[{"id":"3508","type":"Disease","text":["pain"],"offsets":[[30,34]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"3509","type":"Disease","text":["pain"],"offsets":[[259,263]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"3510","type":"Disease","text":["tissue injury"],"offsets":[[300,313]],"normalized":[{"db_name":"MESH","db_id":"D017695"}]},{"id":"3511","type":"Disease","text":["secondary hyperalgesia"],"offsets":[[315,337]],"normalized":[{"db_name":"MESH","db_id":"D006930"}]},{"id":"3512","type":"Disease","text":["Secondary hyperalgesia"],"offsets":[[340,362]],"normalized":[{"db_name":"MESH","db_id":"D006930"}]},{"id":"3513","type":"Disease","text":["neurogenic hyperalgesia"],"offsets":[[400,423]],"normalized":[{"db_name":"MESH","db_id":"D006930"}]},{"id":"3514","type":"Disease","text":["neuropathic pain"],"offsets":[[441,457]],"normalized":[{"db_name":"MESH","db_id":"D009437"}]},{"id":"3515","type":"Disease","text":["hyperalgesia"],"offsets":[[542,554]],"normalized":[{"db_name":"MESH","db_id":"D006930"}]},{"id":"3516","type":"Chemical","text":["gabapentin"],"offsets":[[679,689]],"normalized":[{"db_name":"MESH","db_id":"C040029"}]},{"id":"3517","type":"Disease","text":["neuropathic pain"],"offsets":[[711,727]],"normalized":[{"db_name":"MESH","db_id":"D009437"}]},{"id":"3518","type":"Chemical","text":["gabapentin"],"offsets":[[917,927]],"normalized":[{"db_name":"MESH","db_id":"C040029"}]},{"id":"3519","type":"Chemical","text":["capsaicin"],"offsets":[[1034,1043]],"normalized":[{"db_name":"MESH","db_id":"D002211"}]},{"id":"3520","type":"Disease","text":["secondary hyperalgesia"],"offsets":[[1052,1074]],"normalized":[{"db_name":"MESH","db_id":"D006930"}]},{"id":"3521","type":"Chemical","text":["gabapentin"],"offsets":[[1088,1098]],"normalized":[{"db_name":"MESH","db_id":"C040029"}]},{"id":"3522","type":"Chemical","text":["gabapentin"],"offsets":[[1166,1176]],"normalized":[{"db_name":"MESH","db_id":"C040029"}]},{"id":"3523","type":"Chemical","text":["gabapentin"],"offsets":[[1303,1313]],"normalized":[{"db_name":"MESH","db_id":"C040029"}]},{"id":"3524","type":"Chemical","text":["gabapentin"],"offsets":[[1396,1406]],"normalized":[{"db_name":"MESH","db_id":"C040029"}]},{"id":"3525","type":"Chemical","text":["gabapentin"],"offsets":[[1666,1676]],"normalized":[{"db_name":"MESH","db_id":"C040029"}]},{"id":"3526","type":"Chemical","text":["gabapentin"],"offsets":[[1846,1856]],"normalized":[{"db_name":"MESH","db_id":"C040029"}]}],"events":[],"coreferences":[],"relations":[{"id":"3527","type":"CID","arg1_id":"3519","arg2_id":"3511","normalized":[]},{"id":"3528","type":"CID","arg1_id":"3519","arg2_id":"3512","normalized":[]},{"id":"3529","type":"CID","arg1_id":"3519","arg2_id":"3513","normalized":[]},{"id":"3530","type":"CID","arg1_id":"3519","arg2_id":"3515","normalized":[]},{"id":"3531","type":"CID","arg1_id":"3519","arg2_id":"3520","normalized":[]}]}
{"id":"3532","document_id":"16574712","passages":[{"id":"3533","type":"title","text":["MDMA polydrug users show process-specific central executive impairments coupled with impaired social and emotional judgement processes."],"offsets":[[0,135]]},{"id":"3534","type":"abstract","text":["In recent years working memory deficits have been reported in users of MDMA (3,4-methylenedioxymethamphetamine, ecstasy). The current study aimed to assess the impact of MDMA use on three separate central executive processes (set shifting, inhibition and memory updating) and also on \"prefrontal\" mediated social and emotional judgement processes. Fifteen polydrug ecstasy users and 15 polydrug non-ecstasy user controls completed a general drug use questionnaire, the Brixton Spatial Anticipation task (set shifting), Backward Digit Span procedure (memory updating), Inhibition of Return (inhibition), an emotional intelligence scale, the Tromso Social Intelligence Scale and the Dysexecutive Questionnaire (DEX). Compared with MDMA-free polydrug controls, MDMA polydrug users showed impairments in set shifting and memory updating, and also in social and emotional judgement processes. The latter two deficits remained significant after controlling for other drug use. These data lend further support to the proposal that cognitive processes mediated by the prefrontal cortex may be impaired by recreational ecstasy use."],"offsets":[[136,1258]]}],"entities":[{"id":"3535","type":"Chemical","text":["MDMA"],"offsets":[[0,4]],"normalized":[{"db_name":"MESH","db_id":"D018817"}]},{"id":"3536","type":"Disease","text":["impaired social and emotional judgement processes"],"offsets":[[85,134]],"normalized":[{"db_name":"MESH","db_id":"D003072"}]},{"id":"3537","type":"Disease","text":["memory deficits"],"offsets":[[160,175]],"normalized":[{"db_name":"MESH","db_id":"D008569"}]},{"id":"3538","type":"Chemical","text":["MDMA"],"offsets":[[207,211]],"normalized":[{"db_name":"MESH","db_id":"D018817"}]},{"id":"3539","type":"Chemical","text":["3,4-methylenedioxymethamphetamine"],"offsets":[[213,246]],"normalized":[{"db_name":"MESH","db_id":"D018817"}]},{"id":"3540","type":"Chemical","text":["ecstasy"],"offsets":[[248,255]],"normalized":[{"db_name":"MESH","db_id":"D018817"}]},{"id":"3541","type":"Chemical","text":["MDMA"],"offsets":[[306,310]],"normalized":[{"db_name":"MESH","db_id":"D018817"}]},{"id":"3542","type":"Chemical","text":["ecstasy"],"offsets":[[501,508]],"normalized":[{"db_name":"MESH","db_id":"D018817"}]},{"id":"3543","type":"Chemical","text":["ecstasy"],"offsets":[[535,542]],"normalized":[{"db_name":"MESH","db_id":"D018817"}]},{"id":"3544","type":"Chemical","text":["MDMA"],"offsets":[[865,869]],"normalized":[{"db_name":"MESH","db_id":"D018817"}]},{"id":"3545","type":"Chemical","text":["MDMA"],"offsets":[[894,898]],"normalized":[{"db_name":"MESH","db_id":"D018817"}]},{"id":"3546","type":"Chemical","text":["ecstasy"],"offsets":[[1246,1253]],"normalized":[{"db_name":"MESH","db_id":"D018817"}]}],"events":[],"coreferences":[],"relations":[{"id":"3547","type":"CID","arg1_id":"3535","arg2_id":"3536","normalized":[]},{"id":"3548","type":"CID","arg1_id":"3538","arg2_id":"3536","normalized":[]},{"id":"3549","type":"CID","arg1_id":"3539","arg2_id":"3536","normalized":[]},{"id":"3550","type":"CID","arg1_id":"3540","arg2_id":"3536","normalized":[]},{"id":"3551","type":"CID","arg1_id":"3541","arg2_id":"3536","normalized":[]},{"id":"3552","type":"CID","arg1_id":"3542","arg2_id":"3536","normalized":[]},{"id":"3553","type":"CID","arg1_id":"3543","arg2_id":"3536","normalized":[]},{"id":"3554","type":"CID","arg1_id":"3544","arg2_id":"3536","normalized":[]},{"id":"3555","type":"CID","arg1_id":"3545","arg2_id":"3536","normalized":[]},{"id":"3556","type":"CID","arg1_id":"3546","arg2_id":"3536","normalized":[]}]}
{"id":"3557","document_id":"17111419","passages":[{"id":"3558","type":"title","text":["Severe citrate toxicity complicating volunteer apheresis platelet donation."],"offsets":[[0,75]]},{"id":"3559","type":"abstract","text":["We report a case of severe citrate toxicity during volunteer donor apheresis platelet collection. The donor was a 40-year-old female, first-time apheresis platelet donor. Past medical history was remarkable for hypertension, hyperlipidemia, and depression. Reported medications included bumetanide, pravastatin, and paroxetine. Thirty minutes from the start of the procedure, the donor noted tingling around the mouth, hands, and feet. She then very rapidly developed acute onset of severe facial and extremity tetany. Empirical treatment with intravenous calcium gluconate was initiated, and muscle contractions slowly subsided over approximately 10 to 15 minutes. The events are consistent with a severe reaction to calcium chelation by sodium citrate anticoagulant resulting in symptomatic systemic hypocalcemia. Upon additional retrospective analysis, it was noted that bumetanide is a loop diuretic that may cause significant hypocalcemia. We conclude that careful screening for medications and underlying conditions predisposing to hypocalcemia is recommended to help prevent severe reactions due to citrate toxicity. Laboratory measurement of pre-procedure serum calcium levels in selected donors may identify cases requiring heightened vigilance. The case also illustrates the importance of maintaining preparedness for managing rare but serious reactions in volunteer apheresis blood donors."],"offsets":[[76,1476]]}],"entities":[{"id":"3560","type":"Chemical","text":["citrate"],"offsets":[[7,14]],"normalized":[{"db_name":"MESH","db_id":"C102006"}]},{"id":"3561","type":"Disease","text":["toxicity"],"offsets":[[15,23]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"3562","type":"Chemical","text":["citrate"],"offsets":[[103,110]],"normalized":[{"db_name":"MESH","db_id":"C102006"}]},{"id":"3563","type":"Disease","text":["toxicity"],"offsets":[[111,119]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"3564","type":"Disease","text":["hypertension"],"offsets":[[287,299]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"3565","type":"Disease","text":["hyperlipidemia"],"offsets":[[301,315]],"normalized":[{"db_name":"MESH","db_id":"D006949"}]},{"id":"3566","type":"Disease","text":["depression"],"offsets":[[321,331]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"3567","type":"Chemical","text":["bumetanide"],"offsets":[[363,373]],"normalized":[{"db_name":"MESH","db_id":"D002034"}]},{"id":"3568","type":"Chemical","text":["pravastatin"],"offsets":[[375,386]],"normalized":[{"db_name":"MESH","db_id":"D017035"}]},{"id":"3569","type":"Chemical","text":["paroxetine"],"offsets":[[392,402]],"normalized":[{"db_name":"MESH","db_id":"D017374"}]},{"id":"3570","type":"Disease","text":["tetany"],"offsets":[[587,593]],"normalized":[{"db_name":"MESH","db_id":"D013746"}]},{"id":"3571","type":"Chemical","text":["calcium gluconate"],"offsets":[[632,649]],"normalized":[{"db_name":"MESH","db_id":"D002125"}]},{"id":"3572","type":"Disease","text":["muscle contractions"],"offsets":[[669,688]],"normalized":[{"db_name":"MESH","db_id":"C536214"}]},{"id":"3573","type":"Chemical","text":["calcium"],"offsets":[[794,801]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"3574","type":"Chemical","text":["sodium citrate"],"offsets":[[815,829]],"normalized":[{"db_name":"MESH","db_id":"C102006"}]},{"id":"3575","type":"Disease","text":["hypocalcemia"],"offsets":[[878,890]],"normalized":[{"db_name":"MESH","db_id":"D006996"}]},{"id":"3576","type":"Chemical","text":["bumetanide"],"offsets":[[950,960]],"normalized":[{"db_name":"MESH","db_id":"D002034"}]},{"id":"3577","type":"Chemical","text":["loop diuretic"],"offsets":[[966,979]],"normalized":[{"db_name":"MESH","db_id":"D049994"}]},{"id":"3578","type":"Disease","text":["hypocalcemia"],"offsets":[[1007,1019]],"normalized":[{"db_name":"MESH","db_id":"D006996"}]},{"id":"3579","type":"Disease","text":["hypocalcemia"],"offsets":[[1114,1126]],"normalized":[{"db_name":"MESH","db_id":"D006996"}]},{"id":"3580","type":"Chemical","text":["citrate"],"offsets":[[1182,1189]],"normalized":[{"db_name":"MESH","db_id":"C102006"}]},{"id":"3581","type":"Disease","text":["toxicity"],"offsets":[[1190,1198]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"3582","type":"Chemical","text":["calcium"],"offsets":[[1246,1253]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]}],"events":[],"coreferences":[],"relations":[{"id":"3583","type":"CID","arg1_id":"3560","arg2_id":"3575","normalized":[]},{"id":"3584","type":"CID","arg1_id":"3560","arg2_id":"3578","normalized":[]},{"id":"3585","type":"CID","arg1_id":"3560","arg2_id":"3579","normalized":[]},{"id":"3586","type":"CID","arg1_id":"3562","arg2_id":"3575","normalized":[]},{"id":"3587","type":"CID","arg1_id":"3562","arg2_id":"3578","normalized":[]},{"id":"3588","type":"CID","arg1_id":"3562","arg2_id":"3579","normalized":[]},{"id":"3589","type":"CID","arg1_id":"3574","arg2_id":"3575","normalized":[]},{"id":"3590","type":"CID","arg1_id":"3574","arg2_id":"3578","normalized":[]},{"id":"3591","type":"CID","arg1_id":"3574","arg2_id":"3579","normalized":[]},{"id":"3592","type":"CID","arg1_id":"3580","arg2_id":"3575","normalized":[]},{"id":"3593","type":"CID","arg1_id":"3580","arg2_id":"3578","normalized":[]},{"id":"3594","type":"CID","arg1_id":"3580","arg2_id":"3579","normalized":[]}]}
{"id":"3595","document_id":"17175308","passages":[{"id":"3596","type":"title","text":["Proteinuria after conversion to sirolimus in renal transplant recipients."],"offsets":[[0,73]]},{"id":"3597","type":"abstract","text":["Sirolimus (SRL) is a new, potent immunosuppressive agent. More recently, proteinuria has been reported as a consequence of sirolimus therapy, although the mechanism has remained unclear. We retrospectively examined the records of 25 renal transplant patients, who developed or displayed increased proteinuria after SRL conversion. The patient cohort (14 men, 11 women) was treated with SRL as conversion therapy, due to chronic allograft nephropathy (CAN) (n = 15) neoplasia (n = 8); Kaposi's sarcoma, Four skin cancers, One intestinal tumors, One renal cell carsinom) or BK virus nephropathy (n = 2). SRL was started at a mean of 78 +\/- 42 (15 to 163) months after transplantation. Mean follow-up on SRL therapy was 20 +\/- 12 (6 to 43) months. Proteinuria increased from 0.445 (0 to 1.5) g\/d before conversion to 3.2 g\/dL (0.2 to 12) after conversion (P = 0.001). Before conversion 8 (32%) patients had no proteinuria, whereas afterwards all patients had proteinuria. In 28% of patients proteinuria remained unchanged, whereas it increased in 68% of patients. In 40% it increased by more than 100%. Twenty-eight percent of patients showed increased proteinuria to the nephrotic range. Biopsies performed in five patients revealed new pathological changes: One membranoproliferative glomerulopathy and interstitial nephritis. These patients showed persistently good graft function. Serum creatinine values did not change significantly: 1.98 +\/- 0.8 mg\/dL before SRL therapy and 2.53 +\/- 1.9 mg\/dL at last follow-up (P = .14). Five grafts were lost and the patients returned to dialysis. Five patients displayed CAN and Kaposi's sarcoma. Mean urinary protein of patients who returned to dialysis was 1.26 (0.5 to 3.5) g\/d before and 4.7 (3 to 12) g\/d after conversion (P = .01). Mean serum creatinine level before conversion was 2.21 mg\/dL and thereafter, 4.93 mg\/dL (P = .02). Heavy proteinuria was common after the use of SRL as rescue therapy for renal transplantation. Therefore, conversion should be considered for patients who have not developed advanced CAN and proteinuria. The possibility of de novo glomerular pathology under SRL treatment requires further investigation by renal biopsy."],"offsets":[[74,2270]]}],"entities":[{"id":"3598","type":"Disease","text":["Proteinuria"],"offsets":[[0,11]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]},{"id":"3599","type":"Chemical","text":["sirolimus"],"offsets":[[32,41]],"normalized":[{"db_name":"MESH","db_id":"D020123"}]},{"id":"3600","type":"Chemical","text":["Sirolimus"],"offsets":[[74,83]],"normalized":[{"db_name":"MESH","db_id":"D020123"}]},{"id":"3601","type":"Chemical","text":["SRL"],"offsets":[[85,88]],"normalized":[{"db_name":"MESH","db_id":"D020123"}]},{"id":"3602","type":"Disease","text":["proteinuria"],"offsets":[[147,158]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]},{"id":"3603","type":"Chemical","text":["sirolimus"],"offsets":[[197,206]],"normalized":[{"db_name":"MESH","db_id":"D020123"}]},{"id":"3604","type":"Disease","text":["proteinuria"],"offsets":[[371,382]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]},{"id":"3605","type":"Chemical","text":["SRL"],"offsets":[[389,392]],"normalized":[{"db_name":"MESH","db_id":"D020123"}]},{"id":"3606","type":"Chemical","text":["SRL"],"offsets":[[460,463]],"normalized":[{"db_name":"MESH","db_id":"D020123"}]},{"id":"3607","type":"Disease","text":["chronic allograft nephropathy"],"offsets":[[494,523]],"normalized":[{"db_name":"MESH","db_id":"D051436"}]},{"id":"3608","type":"Disease","text":["CAN"],"offsets":[[525,528]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"3609","type":"Disease","text":["neoplasia"],"offsets":[[539,548]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"3610","type":"Disease","text":["Kaposi's sarcoma"],"offsets":[[558,574]],"normalized":[{"db_name":"MESH","db_id":"D012514"}]},{"id":"3611","type":"Disease","text":["skin cancers"],"offsets":[[581,593]],"normalized":[{"db_name":"MESH","db_id":"D012878"}]},{"id":"3612","type":"Disease","text":["intestinal tumors"],"offsets":[[599,616]],"normalized":[{"db_name":"MESH","db_id":"D007414"}]},{"id":"3613","type":"Disease","text":["renal cell carsinom"],"offsets":[[622,641]],"normalized":[{"db_name":"MESH","db_id":"D002292"}]},{"id":"3614","type":"Disease","text":["nephropathy"],"offsets":[[655,666]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"3615","type":"Chemical","text":["SRL"],"offsets":[[676,679]],"normalized":[{"db_name":"MESH","db_id":"D020123"}]},{"id":"3616","type":"Chemical","text":["SRL"],"offsets":[[775,778]],"normalized":[{"db_name":"MESH","db_id":"D020123"}]},{"id":"3617","type":"Disease","text":["Proteinuria"],"offsets":[[819,830]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]},{"id":"3618","type":"Disease","text":["proteinuria"],"offsets":[[981,992]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]},{"id":"3619","type":"Disease","text":["proteinuria"],"offsets":[[1030,1041]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]},{"id":"3620","type":"Disease","text":["proteinuria"],"offsets":[[1062,1073]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]},{"id":"3621","type":"Disease","text":["proteinuria"],"offsets":[[1224,1235]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]},{"id":"3622","type":"Disease","text":["nephrotic"],"offsets":[[1243,1252]],"normalized":[{"db_name":"MESH","db_id":"D009404"}]},{"id":"3623","type":"Disease","text":["membranoproliferative glomerulopathy"],"offsets":[[1335,1371]],"normalized":[{"db_name":"MESH","db_id":"D015433"}]},{"id":"3624","type":"Disease","text":["interstitial nephritis"],"offsets":[[1376,1398]],"normalized":[{"db_name":"MESH","db_id":"D009395"}]},{"id":"3625","type":"Chemical","text":["creatinine"],"offsets":[[1462,1472]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"3626","type":"Chemical","text":["SRL"],"offsets":[[1536,1539]],"normalized":[{"db_name":"MESH","db_id":"D020123"}]},{"id":"3627","type":"Disease","text":["CAN"],"offsets":[[1685,1688]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"3628","type":"Disease","text":["Kaposi's sarcoma"],"offsets":[[1693,1709]],"normalized":[{"db_name":"MESH","db_id":"D012514"}]},{"id":"3629","type":"Chemical","text":["creatinine"],"offsets":[[1863,1873]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"3630","type":"Disease","text":["proteinuria"],"offsets":[[1957,1968]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]},{"id":"3631","type":"Chemical","text":["SRL"],"offsets":[[1997,2000]],"normalized":[{"db_name":"MESH","db_id":"D020123"}]},{"id":"3632","type":"Disease","text":["CAN"],"offsets":[[2134,2137]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"3633","type":"Disease","text":["proteinuria"],"offsets":[[2142,2153]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]},{"id":"3634","type":"Chemical","text":["SRL"],"offsets":[[2209,2212]],"normalized":[{"db_name":"MESH","db_id":"D020123"}]}],"events":[],"coreferences":[],"relations":[{"id":"3635","type":"CID","arg1_id":"3599","arg2_id":"3598","normalized":[]},{"id":"3636","type":"CID","arg1_id":"3599","arg2_id":"3602","normalized":[]},{"id":"3637","type":"CID","arg1_id":"3599","arg2_id":"3604","normalized":[]},{"id":"3638","type":"CID","arg1_id":"3599","arg2_id":"3617","normalized":[]},{"id":"3639","type":"CID","arg1_id":"3599","arg2_id":"3618","normalized":[]},{"id":"3640","type":"CID","arg1_id":"3599","arg2_id":"3619","normalized":[]},{"id":"3641","type":"CID","arg1_id":"3599","arg2_id":"3620","normalized":[]},{"id":"3642","type":"CID","arg1_id":"3599","arg2_id":"3621","normalized":[]},{"id":"3643","type":"CID","arg1_id":"3599","arg2_id":"3630","normalized":[]},{"id":"3644","type":"CID","arg1_id":"3599","arg2_id":"3633","normalized":[]},{"id":"3645","type":"CID","arg1_id":"3600","arg2_id":"3598","normalized":[]},{"id":"3646","type":"CID","arg1_id":"3600","arg2_id":"3602","normalized":[]},{"id":"3647","type":"CID","arg1_id":"3600","arg2_id":"3604","normalized":[]},{"id":"3648","type":"CID","arg1_id":"3600","arg2_id":"3617","normalized":[]},{"id":"3649","type":"CID","arg1_id":"3600","arg2_id":"3618","normalized":[]},{"id":"3650","type":"CID","arg1_id":"3600","arg2_id":"3619","normalized":[]},{"id":"3651","type":"CID","arg1_id":"3600","arg2_id":"3620","normalized":[]},{"id":"3652","type":"CID","arg1_id":"3600","arg2_id":"3621","normalized":[]},{"id":"3653","type":"CID","arg1_id":"3600","arg2_id":"3630","normalized":[]},{"id":"3654","type":"CID","arg1_id":"3600","arg2_id":"3633","normalized":[]},{"id":"3655","type":"CID","arg1_id":"3601","arg2_id":"3598","normalized":[]},{"id":"3656","type":"CID","arg1_id":"3601","arg2_id":"3602","normalized":[]},{"id":"3657","type":"CID","arg1_id":"3601","arg2_id":"3604","normalized":[]},{"id":"3658","type":"CID","arg1_id":"3601","arg2_id":"3617","normalized":[]},{"id":"3659","type":"CID","arg1_id":"3601","arg2_id":"3618","normalized":[]},{"id":"3660","type":"CID","arg1_id":"3601","arg2_id":"3619","normalized":[]},{"id":"3661","type":"CID","arg1_id":"3601","arg2_id":"3620","normalized":[]},{"id":"3662","type":"CID","arg1_id":"3601","arg2_id":"3621","normalized":[]},{"id":"3663","type":"CID","arg1_id":"3601","arg2_id":"3630","normalized":[]},{"id":"3664","type":"CID","arg1_id":"3601","arg2_id":"3633","normalized":[]},{"id":"3665","type":"CID","arg1_id":"3603","arg2_id":"3598","normalized":[]},{"id":"3666","type":"CID","arg1_id":"3603","arg2_id":"3602","normalized":[]},{"id":"3667","type":"CID","arg1_id":"3603","arg2_id":"3604","normalized":[]},{"id":"3668","type":"CID","arg1_id":"3603","arg2_id":"3617","normalized":[]},{"id":"3669","type":"CID","arg1_id":"3603","arg2_id":"3618","normalized":[]},{"id":"3670","type":"CID","arg1_id":"3603","arg2_id":"3619","normalized":[]},{"id":"3671","type":"CID","arg1_id":"3603","arg2_id":"3620","normalized":[]},{"id":"3672","type":"CID","arg1_id":"3603","arg2_id":"3621","normalized":[]},{"id":"3673","type":"CID","arg1_id":"3603","arg2_id":"3630","normalized":[]},{"id":"3674","type":"CID","arg1_id":"3603","arg2_id":"3633","normalized":[]},{"id":"3675","type":"CID","arg1_id":"3605","arg2_id":"3598","normalized":[]},{"id":"3676","type":"CID","arg1_id":"3605","arg2_id":"3602","normalized":[]},{"id":"3677","type":"CID","arg1_id":"3605","arg2_id":"3604","normalized":[]},{"id":"3678","type":"CID","arg1_id":"3605","arg2_id":"3617","normalized":[]},{"id":"3679","type":"CID","arg1_id":"3605","arg2_id":"3618","normalized":[]},{"id":"3680","type":"CID","arg1_id":"3605","arg2_id":"3619","normalized":[]},{"id":"3681","type":"CID","arg1_id":"3605","arg2_id":"3620","normalized":[]},{"id":"3682","type":"CID","arg1_id":"3605","arg2_id":"3621","normalized":[]},{"id":"3683","type":"CID","arg1_id":"3605","arg2_id":"3630","normalized":[]},{"id":"3684","type":"CID","arg1_id":"3605","arg2_id":"3633","normalized":[]},{"id":"3685","type":"CID","arg1_id":"3606","arg2_id":"3598","normalized":[]},{"id":"3686","type":"CID","arg1_id":"3606","arg2_id":"3602","normalized":[]},{"id":"3687","type":"CID","arg1_id":"3606","arg2_id":"3604","normalized":[]},{"id":"3688","type":"CID","arg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{"id":"3745","document_id":"17244258","passages":[{"id":"3746","type":"title","text":["In vitro characterization of parasympathetic and sympathetic responses in cyclophosphamide-induced cystitis in the rat."],"offsets":[[0,119]]},{"id":"3747","type":"abstract","text":["In cyclophosphamide-induced cystitis in the rat, detrusor function is impaired and the expression and effects of muscarinic receptors altered. Whether or not the neuronal transmission may be affected by cystitis was presently investigated. Responses of urinary strip preparations from control and cyclophosphamide-pretreated rats to electrical field stimulation and to agonists were assessed in the absence and presence of muscarinic, adrenergic and purinergic receptor antagonists. Generally, atropine reduced contractions, but in contrast to controls, it also reduced responses to low electrical field stimulation intensity (1-5 Hz) in inflamed preparations. In both types, purinoceptor desensitization with alpha,beta-methylene adenosine-5'-triphosphate (alpha,beta-meATP) caused further reductions at low frequencies (<10 Hz). The muscarinic receptor antagonists atropine, 4-diphenylacetoxy-N-methylpiperidine (4-DAMP) ('M(1)\/M(3)\/M(5)-selective'), methoctramine ('M(2)-selective') and pirenzepine ('M(1)-selective') antagonized the tonic component of the electrical field stimulation-evoked contractile response more potently than the phasic component. 4-DAMP inhibited the tonic contractions in controls more potently than methoctramine and pirenzepine. In inflamed preparations, the muscarinic receptor antagonism on the phasic component of the electrical field stimulation-evoked contraction was decreased and the pirenzepine and 4-DAMP antagonism on the tonic component was much less efficient than in controls. In contrast to controls, methoctramine increased -- instead of decreased -- the tonic responses at high frequencies. While contractions to carbachol and ATP were the same in inflamed and in control strips when related to a reference potassium response, isoprenaline-induced relaxations were smaller in inflamed strips. Thus, in cystitis substantial changes of the efferent functional responses occur. While postjunctional beta-adrenoceptor-mediated relaxations are reduced, effects by prejunctional inhibitory muscarinic receptors may be increased."],"offsets":[[120,2189]]}],"entities":[{"id":"3748","type":"Chemical","text":["cyclophosphamide"],"offsets":[[74,90]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"3749","type":"Disease","text":["cystitis"],"offsets":[[99,107]],"normalized":[{"db_name":"MESH","db_id":"D003556"}]},{"id":"3750","type":"Chemical","text":["cyclophosphamide"],"offsets":[[123,139]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"3751","type":"Disease","text":["cystitis"],"offsets":[[148,156]],"normalized":[{"db_name":"MESH","db_id":"D003556"}]},{"id":"3752","type":"Disease","text":["cystitis"],"offsets":[[323,331]],"normalized":[{"db_name":"MESH","db_id":"D003556"}]},{"id":"3753","type":"Chemical","text":["cyclophosphamide"],"offsets":[[417,433]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"3754","type":"Chemical","text":["atropine"],"offsets":[[614,622]],"normalized":[{"db_name":"MESH","db_id":"D001285"}]},{"id":"3755","type":"Chemical","text":["alpha,beta-methylene adenosine-5'-triphosphate"],"offsets":[[830,876]],"normalized":[{"db_name":"MESH","db_id":"C002630"}]},{"id":"3756","type":"Chemical","text":["alpha,beta-meATP"],"offsets":[[878,894]],"normalized":[{"db_name":"MESH","db_id":"C002630"}]},{"id":"3757","type":"Chemical","text":["atropine"],"offsets":[[987,995]],"normalized":[{"db_name":"MESH","db_id":"D001285"}]},{"id":"3758","type":"Chemical","text":["4-diphenylacetoxy-N-methylpiperidine"],"offsets":[[997,1033]],"normalized":[{"db_name":"MESH","db_id":"C042375"}]},{"id":"3759","type":"Chemical","text":["4-DAMP"],"offsets":[[1035,1041]],"normalized":[{"db_name":"MESH","db_id":"C042375"}]},{"id":"3760","type":"Chemical","text":["methoctramine"],"offsets":[[1073,1086]],"normalized":[{"db_name":"MESH","db_id":"C054938"}]},{"id":"3761","type":"Chemical","text":["pirenzepine"],"offsets":[[1110,1121]],"normalized":[{"db_name":"MESH","db_id":"D010890"}]},{"id":"3762","type":"Chemical","text":["4-DAMP"],"offsets":[[1278,1284]],"normalized":[{"db_name":"MESH","db_id":"C042375"}]},{"id":"3763","type":"Chemical","text":["methoctramine"],"offsets":[[1349,1362]],"normalized":[{"db_name":"MESH","db_id":"C054938"}]},{"id":"3764","type":"Chemical","text":["pirenzepine"],"offsets":[[1367,1378]],"normalized":[{"db_name":"MESH","db_id":"D010890"}]},{"id":"3765","type":"Chemical","text":["pirenzepine"],"offsets":[[1542,1553]],"normalized":[{"db_name":"MESH","db_id":"D010890"}]},{"id":"3766","type":"Chemical","text":["4-DAMP"],"offsets":[[1558,1564]],"normalized":[{"db_name":"MESH","db_id":"C042375"}]},{"id":"3767","type":"Chemical","text":["methoctramine"],"offsets":[[1666,1679]],"normalized":[{"db_name":"MESH","db_id":"C054938"}]},{"id":"3768","type":"Chemical","text":["carbachol"],"offsets":[[1780,1789]],"normalized":[{"db_name":"MESH","db_id":"D002217"}]},{"id":"3769","type":"Chemical","text":["ATP"],"offsets":[[1794,1797]],"normalized":[{"db_name":"MESH","db_id":"D000255"}]},{"id":"3770","type":"Chemical","text":["potassium"],"offsets":[[1874,1883]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"3771","type":"Chemical","text":["isoprenaline"],"offsets":[[1894,1906]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"3772","type":"Disease","text":["cystitis"],"offsets":[[1969,1977]],"normalized":[{"db_name":"MESH","db_id":"D003556"}]}],"events":[],"coreferences":[],"relations":[{"id":"3773","type":"CID","arg1_id":"3748","arg2_id":"3749","normalized":[]},{"id":"3774","type":"CID","arg1_id":"3748","arg2_id":"3751","normalized":[]},{"id":"3775","type":"CID","arg1_id":"3748","arg2_id":"3752","normalized":[]},{"id":"3776","type":"CID","arg1_id":"3748","arg2_id":"3772","normalized":[]},{"id":"3777","type":"CID","arg1_id":"3750","arg2_id":"3749","normalized":[]},{"id":"3778","type":"CID","arg1_id":"3750","arg2_id":"3751","normalized":[]},{"id":"3779","type":"CID","arg1_id":"3750","arg2_id":"3752","normalized":[]},{"id":"3780","type":"CID","arg1_id":"3750","arg2_id":"3772","normalized":[]},{"id":"3781","type":"CID","arg1_id":"3753","arg2_id":"3749","normalized":[]},{"id":"3782","type":"CID","arg1_id":"3753","arg2_id":"3751","normalized":[]},{"id":"3783","type":"CID","arg1_id":"3753","arg2_id":"3752","normalized":[]},{"id":"3784","type":"CID","arg1_id":"3753","arg2_id":"3772","normalized":[]}]}
{"id":"3785","document_id":"18020536","passages":[{"id":"3786","type":"title","text":["Associations between use of benzodiazepines or related drugs and health, physical abilities and cognitive function: a non-randomised clinical study in the elderly."],"offsets":[[0,163]]},{"id":"3787","type":"abstract","text":["OBJECTIVE: To describe associations between the use of benzodiazepines or related drugs (BZDs\/RDs) and health, functional abilities and cognitive function in the elderly. METHODS: A non-randomised clinical study of patients aged > or =65 years admitted to acute hospital wards during 1 month. 164 patients (mean age +\/- standard deviation [SD] 81.6 +\/- 6.8 years) were admitted. Of these, nearly half (n = 78) had used BZDs\/RDs before admission, and the remainder (n = 86) were non-users. Cognitive ability was assessed by the Mini-Mental State Examination (MMSE). Patients scoring > or =20 MMSE sum points were interviewed (n = 79) and questioned regarding symptoms and functional abilities during the week prior to admission. Data on use of BZDs\/RDs before admission, current medications and discharge diagnoses were collected from medical records. Health, physical abilities and cognitive function were compared between BZD\/RD users and non-users, and adjustments were made for confounding variables. The residual serum concentrations of oxazepam, temazepam and zopiclone were analysed. RESULTS: The mean +\/- SD duration of BZD\/RD use was 7 +\/- 7 years (range 1-31). Two or three BZDs\/RDs were concomitantly taken by 26% of users (n = 20). Long-term use of these drugs was associated with female sex and use of a higher number of drugs with effects on the CNS, which tended to be related to diagnosed dementia. After adjustment for these variables as confounders, use of BZDs\/RDs was not associated with cognitive function as measured by the MMSE. However, use of BZDs\/RDs was associated with dizziness, inability to sleep after awaking at night and tiredness in the mornings during the week prior to admission and with stronger depressive symptoms measured at the beginning of the hospital stay. Use of BZDs\/RDs tended to be associated with a reduced ability to walk and shorter night-time sleep during the week prior to admission. A higher residual serum concentration of temazepam correlated with a lower MMSE sum score after adjustment for confounding variables. CONCLUSIONS: Long-term use and concomitant use of more than one BZD\/RD were common in elderly patients hospitalised because of acute illnesses. Long-term use was associated with daytime and night-time symptoms indicative of poorer health and potentially caused by the adverse effects of these drugs."],"offsets":[[164,2533]]}],"entities":[{"id":"3788","type":"Chemical","text":["benzodiazepines"],"offsets":[[28,43]],"normalized":[{"db_name":"MESH","db_id":"D001569"}]},{"id":"3789","type":"Chemical","text":["benzodiazepines"],"offsets":[[219,234]],"normalized":[{"db_name":"MESH","db_id":"D001569"}]},{"id":"3790","type":"Chemical","text":["BZDs"],"offsets":[[253,257]],"normalized":[{"db_name":"MESH","db_id":"D001569"}]},{"id":"3791","type":"Chemical","text":["BZDs"],"offsets":[[583,587]],"normalized":[{"db_name":"MESH","db_id":"D001569"}]},{"id":"3792","type":"Chemical","text":["BZDs"],"offsets":[[907,911]],"normalized":[{"db_name":"MESH","db_id":"D001569"}]},{"id":"3793","type":"Chemical","text":["oxazepam"],"offsets":[[1205,1213]],"normalized":[{"db_name":"MESH","db_id":"D010076"}]},{"id":"3794","type":"Chemical","text":["temazepam"],"offsets":[[1215,1224]],"normalized":[{"db_name":"MESH","db_id":"D013693"}]},{"id":"3795","type":"Chemical","text":["zopiclone"],"offsets":[[1229,1238]],"normalized":[{"db_name":"MESH","db_id":"C515050"}]},{"id":"3796","type":"Chemical","text":["BZDs"],"offsets":[[1347,1351]],"normalized":[{"db_name":"MESH","db_id":"D001569"}]},{"id":"3797","type":"Disease","text":["dementia"],"offsets":[[1568,1576]],"normalized":[{"db_name":"MESH","db_id":"D003704"}]},{"id":"3798","type":"Chemical","text":["BZDs"],"offsets":[[1638,1642]],"normalized":[{"db_name":"MESH","db_id":"D001569"}]},{"id":"3799","type":"Chemical","text":["BZDs"],"offsets":[[1731,1735]],"normalized":[{"db_name":"MESH","db_id":"D001569"}]},{"id":"3800","type":"Disease","text":["dizziness"],"offsets":[[1760,1769]],"normalized":[{"db_name":"MESH","db_id":"D004244"}]},{"id":"3801","type":"Disease","text":["inability to sleep"],"offsets":[[1771,1789]],"normalized":[{"db_name":"MESH","db_id":"D007319"}]},{"id":"3802","type":"Disease","text":["tiredness"],"offsets":[[1817,1826]],"normalized":[{"db_name":"MESH","db_id":"D005221"}]},{"id":"3803","type":"Disease","text":["depressive symptoms"],"offsets":[[1896,1915]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"3804","type":"Chemical","text":["BZDs"],"offsets":[[1971,1975]],"normalized":[{"db_name":"MESH","db_id":"D001569"}]},{"id":"3805","type":"Chemical","text":["temazepam"],"offsets":[[2141,2150]],"normalized":[{"db_name":"MESH","db_id":"D013693"}]}],"events":[],"coreferences":[],"relations":[{"id":"3806","type":"CID","arg1_id":"3788","arg2_id":"3802","normalized":[]},{"id":"3807","type":"CID","arg1_id":"3789","arg2_id":"3802","normalized":[]},{"id":"3808","type":"CID","arg1_id":"3790","arg2_id":"3802","normalized":[]},{"id":"3809","type":"CID","arg1_id":"3791","arg2_id":"3802","normalized":[]},{"id":"3810","type":"CID","arg1_id":"3792","arg2_id":"3802","normalized":[]},{"id":"3811","type":"CID","arg1_id":"3796","arg2_id":"3802","normalized":[]},{"id":"3812","type":"CID","arg1_id":"3798","arg2_id":"3802","normalized":[]},{"id":"3813","type":"CID","arg1_id":"3799","arg2_id":"3802","normalized":[]},{"id":"3814","type":"CID","arg1_id":"3804","arg2_id":"3802","normalized":[]},{"id":"3815","type":"CID","arg1_id":"3788","arg2_id":"3803","normalized":[]},{"id":"3816","type":"CID","arg1_id":"3789","arg2_id":"3803","normalized":[]},{"id":"3817","type":"CID","arg1_id":"3790","arg2_id":"3803","normalized":[]},{"id":"3818","type":"CID","arg1_id":"3791","arg2_id":"3803","normalized":[]},{"id":"3819","type":"CID","arg1_id":"3792","arg2_id":"3803","normalized":[]},{"id":"3820","type":"CID","arg1_id":"3796","arg2_id":"3803","normalized":[]},{"id":"3821","type":"CID","arg1_id":"3798","arg2_id":"3803","normalized":[]},{"id":"3822","type":"CID","arg1_id":"3799","arg2_id":"3803","normalized":[]},{"id":"3823","type":"CID","arg1_id":"3804","arg2_id":"3803","normalized":[]},{"id":"3824","type":"CID","arg1_id":"3788","arg2_id":"3801","normalized":[]},{"id":"3825","type":"CID","arg1_id":"3789","arg2_id":"3801","normalized":[]},{"id":"3826","type":"CID","arg1_id":"3790","arg2_id":"3801","normalized":[]},{"id":"3827","type":"CID","arg1_id":"3791","arg2_id":"3801","normalized":[]},{"id":"3828","type":"CID","arg1_id":"3792","arg2_id":"3801","normalized":[]},{"id":"3829","type":"CID","arg1_id":"3796","arg2_id":"3801","normalized":[]},{"id":"3830","type":"CID","arg1_id":"3798","arg2_id":"3801","normalized":[]},{"id":"3831","type":"CID","arg1_id":"3799","arg2_id":"3801","normalized":[]},{"id":"3832","type":"CID","arg1_id":"3804","arg2_id":"3801","normalized":[]},{"id":"3833","type":"CID","arg1_id":"3788","arg2_id":"3800","normalized":[]},{"id":"3834","type":"CID","arg1_id":"3789","arg2_id":"3800","normalized":[]},{"id":"3835","type":"CID","arg1_id":"3790","arg2_id":"3800","normalized":[]},{"id":"3836","type":"CID","arg1_id":"3791","arg2_id":"3800","normalized":[]},{"id":"3837","type":"CID","arg1_id":"3792","arg2_id":"3800","normalized":[]},{"id":"3838","type":"CID","arg1_id":"3796","arg2_id":"3800","normalized":[]},{"id":"3839","type":"CID","arg1_id":"3798","arg2_id":"3800","normalized":[]},{"id":"3840","type":"CID","arg1_id":"3799","arg2_id":"3800","normalized":[]},{"id":"3841","type":"CID","arg1_id":"3804","arg2_id":"3800","normalized":[]}]}
{"id":"3842","document_id":"18023325","passages":[{"id":"3843","type":"title","text":["Acute vocal fold palsy after acute disulfiram intoxication."],"offsets":[[0,59]]},{"id":"3844","type":"abstract","text":["Acute peripheral neuropathy caused by a disulfiram overdose is very rare and there is no report of it leading to vocal fold palsy. A 49-year-old woman was transferred to our department because of quadriparesis, lancinating pain, sensory loss, and paresthesia of the distal limbs. One month previously, she had taken a single high dose of disulfiram (130 tablets of ALCOHOL STOP TAB, Shin-Poong Pharm. Co., Ansan, Korea) in a suicide attempt. She was not an alcoholic. For the first few days after ingestion, she was in a confused state and had mild to moderate ataxia and giddiness. She noticed hoarseness and distally accentuated motor and sensory dysfunction after she had recovered from this state. A nerve conduction study was consistent with severe sensorimotor axonal polyneuropathy. Laryngeal electromyography (thyroarytenoid muscle) showed ample denervation potentials. Laryngoscopy revealed asymmetric vocal fold movements during phonation. Her vocal change and weakness began to improve spontaneously about 3 weeks after transfer. This was a case of acute palsy of the recurrent laryngeal nerve and superimposed severe acute sensorimotor axonal polyneuropathy caused by high-dose disulfiram intoxication."],"offsets":[[60,1274]]}],"entities":[{"id":"3845","type":"Disease","text":["vocal fold palsy"],"offsets":[[6,22]],"normalized":[{"db_name":"MESH","db_id":"D014826"}]},{"id":"3846","type":"Chemical","text":["disulfiram"],"offsets":[[35,45]],"normalized":[{"db_name":"MESH","db_id":"D004221"}]},{"id":"3847","type":"Disease","text":["peripheral neuropathy"],"offsets":[[66,87]],"normalized":[{"db_name":"MESH","db_id":"D010523"}]},{"id":"3848","type":"Chemical","text":["disulfiram"],"offsets":[[100,110]],"normalized":[{"db_name":"MESH","db_id":"D004221"}]},{"id":"3849","type":"Disease","text":["overdose"],"offsets":[[111,119]],"normalized":[{"db_name":"MESH","db_id":"D062787"}]},{"id":"3850","type":"Disease","text":["vocal fold palsy"],"offsets":[[173,189]],"normalized":[{"db_name":"MESH","db_id":"D014826"}]},{"id":"3851","type":"Disease","text":["quadriparesis"],"offsets":[[256,269]],"normalized":[{"db_name":"MESH","db_id":"D011782"}]},{"id":"3852","type":"Disease","text":["pain"],"offsets":[[283,287]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"3853","type":"Disease","text":["sensory loss"],"offsets":[[289,301]],"normalized":[{"db_name":"MESH","db_id":"C580162"}]},{"id":"3854","type":"Disease","text":["paresthesia"],"offsets":[[307,318]],"normalized":[{"db_name":"MESH","db_id":"D010292"}]},{"id":"3855","type":"Chemical","text":["disulfiram"],"offsets":[[398,408]],"normalized":[{"db_name":"MESH","db_id":"D004221"}]},{"id":"3856","type":"Chemical","text":["ALCOHOL"],"offsets":[[425,432]],"normalized":[{"db_name":"MESH","db_id":"D000431"}]},{"id":"3857","type":"Disease","text":["ataxia"],"offsets":[[621,627]],"normalized":[{"db_name":"MESH","db_id":"D001259"}]},{"id":"3858","type":"Disease","text":["giddiness"],"offsets":[[632,641]],"normalized":[{"db_name":"MESH","db_id":"D004244"}]},{"id":"3859","type":"Disease","text":["hoarseness"],"offsets":[[655,665]],"normalized":[{"db_name":"MESH","db_id":"D006685"}]},{"id":"3860","type":"Disease","text":["polyneuropathy"],"offsets":[[834,848]],"normalized":[{"db_name":"MESH","db_id":"D011115"}]},{"id":"3861","type":"Disease","text":["palsy"],"offsets":[[1126,1131]],"normalized":[{"db_name":"MESH","db_id":"D010243"}]},{"id":"3862","type":"Disease","text":["polyneuropathy"],"offsets":[[1215,1229]],"normalized":[{"db_name":"MESH","db_id":"D011115"}]},{"id":"3863","type":"Chemical","text":["disulfiram"],"offsets":[[1250,1260]],"normalized":[{"db_name":"MESH","db_id":"D004221"}]}],"events":[],"coreferences":[],"relations":[{"id":"3864","type":"CID","arg1_id":"3846","arg2_id":"3854","normalized":[]},{"id":"3865","type":"CID","arg1_id":"3848","arg2_id":"3854","normalized":[]},{"id":"3866","type":"CID","arg1_id":"3855","arg2_id":"3854","normalized":[]},{"id":"3867","type":"CID","arg1_id":"3863","arg2_id":"3854","normalized":[]},{"id":"3868","type":"CID","arg1_id":"3846","arg2_id":"3851","normalized":[]},{"id":"3869","type":"CID","arg1_id":"3848","arg2_id":"3851","normalized":[]},{"id":"3870","type":"CID","arg1_id":"3855","arg2_id":"3851","normalized":[]},{"id":"3871","type":"CID","arg1_id":"3863","arg2_id":"3851","normalized":[]},{"id":"3872","type":"CID","arg1_id":"3846","arg2_id":"3852","normalized":[]},{"id":"3873","type":"CID","arg1_id":"3848","arg2_id":"3852","normalized":[]},{"id":"3874","type":"CID","arg1_id":"3855","arg2_id":"3852","normalized":[]},{"id":"3875","type":"CID","arg1_id":"3863","arg2_id":"3852","normalized":[]},{"id":"3876","type":"CID","arg1_id":"3846","arg2_id":"3847","normalized":[]},{"id":"3877","type":"CID","arg1_id":"3848","arg2_id":"3847","normalized":[]},{"id":"3878","type":"CID","arg1_id":"3855","arg2_id":"3847","normalized":[]},{"id":"3879","type":"CID","arg1_id":"3863","arg2_id":"3847","normalized":[]},{"id":"3880","type":"CID","arg1_id":"3846","arg2_id":"3857","normalized":[]},{"id":"3881","type":"CID","arg1_id":"3848","arg2_id":"3857","normalized":[]},{"id":"3882","type":"CID","arg1_id":"3855","arg2_id":"3857","normalized":[]},{"id":"3883","type":"CID","arg1_id":"3863","arg2_id":"3857","normalized":[]},{"id":"3884","type":"CID","arg1_id":"3846","arg2_id":"3845","normalized":[]},{"id":"3885","type":"CID","arg1_id":"3846","arg2_id":"3850","normalized":[]},{"id":"3886","type":"CID","arg1_id":"3848","arg2_id":"3845","normalized":[]},{"id":"3887","type":"CID","arg1_id":"3848","arg2_id":"3850","normalized":[]},{"id":"3888","type":"CID","arg1_id":"3855","arg2_id":"3845","normalized":[]},{"id":"3889","type":"CID","arg1_id":"3855","arg2_id":"3850","normalized":[]},{"id":"3890","type":"CID","arg1_id":"3863","arg2_id":"3845","normalized":[]},{"id":"3891","type":"CID","arg1_id":"3863","arg2_id":"3850","normalized":[]}]}
{"id":"3892","document_id":"18208574","passages":[{"id":"3893","type":"title","text":["Higher optical density of an antigen assay predicts thrombosis in patients with heparin-induced thrombocytopenia."],"offsets":[[0,113]]},{"id":"3894","type":"abstract","text":["OBJECTIVES: To correlate optical density and percent inhibition of a two-step heparin-induced thrombocytopenia (HIT) antigen assay with thrombosis; the assay utilizes reaction inhibition characteristics of a high heparin concentration. PATIENTS AND METHODS: Patients with more than 50% decrease in platelet count or thrombocytopenia (<150 x 10(9)\/L) after exposure to heparin, who had a positive two-step antigen assay [optical density (OD) >0.4 and >50 inhibition with high concentration of heparin] were included in the study. RESULTS: Forty of 94 HIT patients had thrombosis at diagnosis; 54\/94 had isolated-HIT without thrombosis. Eight of the isolated-HIT patients developed thrombosis within the next 30 d; thus, a total of 48 patients had thrombosis at day 30. At diagnosis there was no significant difference in OD between HIT patients with thrombosis and those with isolated-HIT. However, OD was significantly higher in all patients with thrombosis (n = 48, 1.34 +\/- 0.89), including isolated-HIT patients who later developed thrombosis within 30 d (n = 8, 1.84 +\/- 0.64) as compared to isolated-HIT patients who did not develop thrombosis (0.96 +\/- 0.75; P = 0.011 and P = 0.008). The Receiver Operative Characteristic Curve showed that OD >1.27 in the isolated-HIT group had a significantly higher chance of developing thrombosis by day 30. None of these groups showed significant difference in percent inhibition. Multivariate analysis showed a 2.8-fold increased risk of thrombosis in females. Similarly, thrombotic risk increased with age and OD values. CONCLUSION: Higher OD is associated with significant risk of subsequent thrombosis in patients with isolated-HIT; percent inhibition, however, was not 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{"id":"4062","document_id":"18343374","passages":[{"id":"4063","type":"title","text":["Central retinal vein occlusion associated with clomiphene-induced ovulation."],"offsets":[[0,76]]},{"id":"4064","type":"abstract","text":["OBJECTIVE: To report a case of central retinal vein occlusion associated with clomiphene citrate (CC). DESIGN: Case study. SETTING: Ophthalmology clinic of an academic hospital. PATIENT(S): A 36-year-old woman referred from the infertility clinic for blurred vision. INTERVENTION(S): Ophthalmic examination after CC therapy. MAIN OUTCOME MEASURE(S): Central retinal vein occlusion after ovulation induction with CC. RESULT(S): A 36-year-old Chinese woman developed central retinal vein occlusion after eight courses of CC. A search of the literature on the thromboembolic complications of CC does not include this severe ophthalmic complication, although mild visual disturbance after CC intake is not uncommon. CONCLUSION(S): This is the first reported case of central retinal vein occlusion after treatment with CC. Extra caution is warranted in treating infertility patients with CC, and patients should be well informed of this side effect before commencement of therapy."],"offsets":[[77,1052]]}],"entities":[{"id":"4065","type":"Disease","text":["retinal vein occlusion"],"offsets":[[8,30]],"normalized":[{"db_name":"MESH","db_id":"D012170"}]},{"id":"4066","type":"Chemical","text":["clomiphene"],"offsets":[[47,57]],"normalized":[{"db_name":"MESH","db_id":"D002996"}]},{"id":"4067","type":"Disease","text":["retinal vein occlusion"],"offsets":[[116,138]],"normalized":[{"db_name":"MESH","db_id":"D012170"}]},{"id":"4068","type":"Chemical","text":["clomiphene 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{"id":"4155","document_id":"18417364","passages":[{"id":"4156","type":"title","text":["Nicotine-induced nystagmus correlates with midpontine activation."],"offsets":[[0,65]]},{"id":"4157","type":"abstract","text":["The pathomechanism of nicotine-induced nystagmus (NIN) is unknown. The aim of this study was to delineate brain structures that are involved in NIN generation. Eight healthy volunteers inhaled nicotine in darkness during a functional magnetic resonance imaging (fMRI) experiment; eye movements were registered using video-oculography. NIN correlated with blood oxygen level-dependent (BOLD) activity levels in a midpontine site in the posterior basis pontis. NIN-induced midpontine activation may correspond to activation of the dorsomedial pontine nuclei and the nucleus reticularis tegmenti pontis, structures known to participate in the generation of multidirectional saccades and smooth pursuit eye movements."],"offsets":[[66,779]]}],"entities":[{"id":"4158","type":"Chemical","text":["Nicotine"],"offsets":[[0,8]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"4159","type":"Disease","text":["nystagmus"],"offsets":[[17,26]],"normalized":[{"db_name":"MESH","db_id":"D009759"}]},{"id":"4160","type":"Chemical","text":["nicotine"],"offsets":[[88,96]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"4161","type":"Disease","text":["nystagmus"],"offsets":[[105,114]],"normalized":[{"db_name":"MESH","db_id":"D009759"}]},{"id":"4162","type":"Disease","text":["NIN"],"offsets":[[116,119]],"normalized":[{"db_name":"MESH","db_id":"D009759"}]},{"id":"4163","type":"Disease","text":["NIN"],"offsets":[[210,213]],"normalized":[{"db_name":"MESH","db_id":"D009759"}]},{"id":"4164","type":"Chemical","text":["nicotine"],"offsets":[[259,267]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"4165","type":"Disease","text":["NIN"],"offsets":[[401,404]],"normalized":[{"db_name":"MESH","db_id":"D009759"}]},{"id":"4166","type":"Chemical","text":["oxygen"],"offsets":[[427,433]],"normalized":[{"db_name":"MESH","db_id":"D010100"}]},{"id":"4167","type":"Disease","text":["NIN"],"offsets":[[525,528]],"normalized":[{"db_name":"MESH","db_id":"D009759"}]}],"events":[],"coreferences":[],"relations":[{"id":"4168","type":"CID","arg1_id":"4158","arg2_id":"4159","normalized":[]},{"id":"4169","type":"CID","arg1_id":"4158","arg2_id":"4161","normalized":[]},{"id":"4170","type":"CID","arg1_id":"4158","arg2_id":"4162","normalized":[]},{"id":"4171","type":"CID","arg1_id":"4158","arg2_id":"4163","normalized":[]},{"id":"4172","type":"CID","arg1_id":"4158","arg2_id":"4165","normalized":[]},{"id":"4173","type":"CID","arg1_id":"4158","arg2_id":"4167","normalized":[]},{"id":"4174","type":"CID","arg1_id":"4160","arg2_id":"4159","normalized":[]},{"id":"4175","type":"CID","arg1_id":"4160","arg2_id":"4161","normalized":[]},{"id":"4176","type":"CID","arg1_id":"4160","arg2_id":"4162","normalized":[]},{"id":"4177","type":"CID","arg1_id":"4160","arg2_id":"4163","normalized":[]},{"id":"4178","type":"CID","arg1_id":"4160","arg2_id":"4165","normalized":[]},{"id":"4179","type":"CID","arg1_id":"4160","arg2_id":"4167","normalized":[]},{"id":"4180","type":"CID","arg1_id":"4164","arg2_id":"4159","normalized":[]},{"id":"4181","type":"CID","arg1_id":"4164","arg2_id":"4161","normalized":[]},{"id":"4182","type":"CID","arg1_id":"4164","arg2_id":"4162","normalized":[]},{"id":"4183","type":"CID","arg1_id":"4164","arg2_id":"4163","normalized":[]},{"id":"4184","type":"CID","arg1_id":"4164","arg2_id":"4165","normalized":[]},{"id":"4185","type":"CID","arg1_id":"4164","arg2_id":"4167","normalized":[]}]}
{"id":"4186","document_id":"18442015","passages":[{"id":"4187","type":"title","text":["Protective effect of verapamil on gastric hemorrhagic ulcers in severe atherosclerotic rats."],"offsets":[[0,92]]},{"id":"4188","type":"abstract","text":["Studies concerning with pathogenesis of gastric hemorrhage and mucosal ulceration produced in atherosclerotic rats are lacking. The aim of this study is to examine the role of gastric acid back-diffusion, mast cell histamine release, lipid peroxide (LPO) generation and mucosal microvascular permeability in modulating gastric hemorrhage and ulcer in rats with atherosclerosis induced by coadministration of vitamin D2 and cholesterol. Additionally, the protective effect of verapamil on this ulcer model was evaluated. Male Wistar rats were challenged intragastrically once daily for 9 days with 1.0 ml\/kg of corn oil containing vitamin D2 and cholesterol to induce atherosclerosis. Control rats received corn oil only. After gastric surgery, rat stomachs were irrigated for 3 h with either simulated gastric juice or normal saline. Gastric acid back-diffusion, mucosal LPO generation, histamine concentration, microvascular permeability, luminal hemoglobin content and ulcer areas were determined. Elevated atherosclerotic parameters, such as serum calcium, total cholesterol and low-density lipoprotein concentration were obtained in atherosclerotic rats. Severe gastric ulcers accompanied with increased ulcerogenic factors, including gastric acid back-diffusion, histamine release, LPO generation and luminal hemoglobin content were also observed in these rats. Moreover, a positive correlation of histamine to gastric hemorrhage and to ulcer was found in those atherosclerotic rats. This hemorrhagic ulcer and various ulcerogenic parameters were dose-dependently ameliorated by daily intragastric verapamil. Atherosclerosis could produce gastric hemorrhagic ulcer via aggravation of gastric acid back-diffusion, LPO generation, histamine release and microvascular permeability that could be ameliorated by verapamil in rats."],"offsets":[[93,1923]]}],"entities":[{"id":"4189","type":"Chemical","text":["verapamil"],"offsets":[[21,30]],"normalized":[{"db_name":"MESH","db_id":"D014700"}]},{"id":"4190","type":"Disease","text":["gastric hemorrhagic"],"offsets":[[34,53]],"normalized":[{"db_name":"MESH","db_id":"D006471"}]},{"id":"4191","type":"Disease","text":["ulcers"],"offsets":[[54,60]],"normalized":[{"db_name":"MESH","db_id":"D014456"}]},{"id":"4192","type":"Disease","text":["atherosclerotic"],"offsets":[[71,86]],"normalized":[{"db_name":"MESH","db_id":"D050197"}]},{"id":"4193","type":"Disease","text":["gastric 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{"id":"4338","document_id":"18619688","passages":[{"id":"4339","type":"title","text":["Adriamycin-induced autophagic cardiomyocyte death plays a pathogenic role in a rat model of heart failure."],"offsets":[[0,106]]},{"id":"4340","type":"abstract","text":["BACKGROUND: The mechanisms underlying heart failure induced by adriamycin are very complicated and still unclear. The aim of this study was to investigate whether autophagy was involved in the progression of heart failure induced by adriamycin, so that we can develop a novel treatment strategy for heart failure. METHODS: 3-methyladenine (3MA), a specific inhibitor on autophagy was used in a heart failure model of rats induced by adriamycin. Neonatal cardiomyocytes were isolated from Sprague-Dawley rat hearts and randomly divided into controls, an adriamycin-treated group, and a 3MA plus adriamycin-treated group. We then examined the morphology, expression of beclin 1 gene, mitochondrial permeability transition (MPT), and Na+-K+ ATPase activity in vivo. We also assessed cell viability, mitochondrial membrane potential changes and counted autophagic vacuoles in cultured cardiomyocytes. In addition, we analyzed the expression of autophagy associated gene, beclin 1 using RT-PCR and Western blotting in an animal model. RESULTS: 3MA significantly improved cardiac function and reduced mitochondrial injury. Furthermore, adriamycin induced the formation of autophagic vacuoles, and 3MA strongly downregulated the expression of beclin 1 in adriamycin-induced failing heart and inhibited the formation of autophagic vacuoles. CONCLUSION: Autophagic cardiomyocyte death plays an important role in the pathogenesis of heart failure in rats induced by adriamycin. Mitochondrial injury may be involved in the progression of heart failure caused by adriamycin via the autophagy pathway."],"offsets":[[107,1695]]}],"entities":[{"id":"4341","type":"Chemical","text":["Adriamycin"],"offsets":[[0,10]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"4342","type":"Disease","text":["death"],"offsets":[[44,49]],"normalized":[{"db_name":"MESH","db_id":"D003643"}]},{"id":"4343","type":"Disease","text":["heart failure"],"offsets":[[92,105]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]},{"id":"4344","type":"Disease","text":["heart failure"],"offsets":[[145,158]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]},{"id":"4345","type":"Chemical","text":["adriamycin"],"offsets":[[170,180]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"4346","type":"Disease","text":["heart 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{"id":"4436","document_id":"19308880","passages":[{"id":"4437","type":"title","text":["Confusion, a rather serious adverse drug reaction with valproic acid: a review of the French Pharmacovigilance database."],"offsets":[[0,120]]},{"id":"4438","type":"abstract","text":["INTRODUCTION: Confusion is an adverse drug reaction frequently observed with valproic acid. Some case reports are published in the literature but no systematic study from a sample of patients has been published. We performed this study in order to describe the main characteristics of this adverse drug reaction. METHODS: Using the French Pharmacovigilance database, we selected the cases of confusion reported since 1985 with valproic acid. RESULTS: 272 cases of confusion were reported with valproic acid: 153 women and 119 men. Confusion mostly occurred during the two first weeks following valproic acid exposure (39.7%). It was \"serious\" for almost 2\/3 of the patients (62.5%) and its outcome favourable in most of the cases (82%). The occurrence of this ADR was more frequent in patients aged between 61 and 80 years. CONCLUSION: This work shows that confusion with valproic acid is a serious, rather frequent but reversible adverse drug reaction. It occurs especially in older patients and during the first two weeks of treatment."],"offsets":[[121,1158]]}],"entities":[{"id":"4439","type":"Disease","text":["Confusion"],"offsets":[[0,9]],"normalized":[{"db_name":"MESH","db_id":"D003221"}]},{"id":"4440","type":"Chemical","text":["valproic acid"],"offsets":[[55,68]],"normalized":[{"db_name":"MESH","db_id":"D014635"}]},{"id":"4441","type":"Disease","text":["Confusion"],"offsets":[[135,144]],"normalized":[{"db_name":"MESH","db_id":"D003221"}]},{"id":"4442","type":"Chemical","text":["valproic acid"],"offsets":[[198,211]],"normalized":[{"db_name":"MESH","db_id":"D014635"}]},{"id":"4443","type":"Disease","text":["confusion"],"offsets":[[513,522]],"normalized":[{"db_name":"MESH","db_id":"D003221"}]},{"id":"4444","type":"Chemical","text":["valproic acid"],"offsets":[[548,561]],"normalized":[{"db_name":"MESH","db_id":"D014635"}]},{"id":"4445","type":"Disease","text":["confusion"],"offsets":[[585,594]],"normalized":[{"db_name":"MESH","db_id":"D003221"}]},{"id":"4446","type":"Chemical","text":["valproic acid"],"offsets":[[614,627]],"normalized":[{"db_name":"MESH","db_id":"D014635"}]},{"id":"4447","type":"Disease","text":["Confusion"],"offsets":[[652,661]],"normalized":[{"db_name":"MESH","db_id":"D003221"}]},{"id":"4448","type":"Chemical","text":["valproic acid"],"offsets":[[715,728]],"normalized":[{"db_name":"MESH","db_id":"D014635"}]},{"id":"4449","type":"Disease","text":["confusion"],"offsets":[[978,987]],"normalized":[{"db_name":"MESH","db_id":"D003221"}]},{"id":"4450","type":"Chemical","text":["valproic acid"],"offsets":[[993,1006]],"normalized":[{"db_name":"MESH","db_id":"D014635"}]}],"events":[],"coreferences":[],"relations":[{"id":"4451","type":"CID","arg1_id":"4440","arg2_id":"4439","normalized":[]},{"id":"4452","type":"CID","arg1_id":"4440","arg2_id":"4441","normalized":[]},{"id":"4453","type":"CID","arg1_id":"4440","arg2_id":"4443","normalized":[]},{"id":"4454","type":"CID","arg1_id":"4440","arg2_id":"4445","normalized":[]},{"id":"4455","type":"CID","arg1_id":"4440","arg2_id":"4447","normalized":[]},{"id":"4456","type":"CID","arg1_id":"4440","arg2_id":"4449","normalized":[]},{"id":"4457","type":"CID","arg1_id":"4442","arg2_id":"4439","normalized":[]},{"id":"4458","type":"CID","arg1_id":"4442","arg2_id":"4441","normalized":[]},{"id":"4459","type":"CID","arg1_id":"4442","arg2_id":"4443","normalized":[]},{"id":"4460","type":"CID","arg1_id":"4442","arg2_id":"4445","normalized":[]},{"id":"4461","type":"CID","arg1_id":"4442","arg2_id":"4447","normalized":[]},{"id":"4462","type":"CID","arg1_id":"4442","arg2_id":"4449","normalized":[]},{"id":"4463","type":"CID","arg1_id":"4444","arg2_id":"4439","normalized":[]},{"id":"4464","type":"CID","arg1_id":"4444","arg2_id":"4441","normalized":[]},{"id":"4465","type":"CID","arg1_id":"4444","arg2_id":"4443","normalized":[]},{"id":"4466","type":"CID","arg1_id":"4444","arg2_id":"4445","normalized":[]},{"id":"4467","type":"CID","arg1_id":"4444","arg2_id":"4447","normalized":[]},{"id":"4468","type":"CID","arg1_id":"4444","arg2_id":"4449","normalized":[]},{"id":"4469","type":"CID","arg1_id":"4446","arg2_id":"4439","normalized":[]},{"id":"4470","type":"CID","arg1_id":"4446","arg2_id":"4441","normalized":[]},{"id":"4471","type":"CID","arg1_id":"4446","arg2_id":"4443","normalized":[]},{"id":"4472","type":"CID","arg1_id":"4446","arg2_id":"4445","normalized":[]},{"id":"4473","type":"CID","arg1_id":"4446","arg2_id":"4447","normalized":[]},{"id":"4474","type":"CID","arg1_id":"4446","arg2_id":"4449","normalized":[]},{"id":"4475","type":"CID","arg1_id":"4448","arg2_id":"4439","normalized":[]},{"id":"4476","type":"CID","arg1_id":"4448","arg2_id":"4441","normalized":[]},{"id":"4477","type":"CID","arg1_id":"4448","arg2_id":"4443","normalized":[]},{"id":"4478","type":"CID","arg1_id":"4448","arg2_id":"4445","normalized":[]},{"id":"4479","type":"CID","arg1_id":"4448","arg2_id":"4447","normalized":[]},{"id":"4480","type":"CID","arg1_id":"4448","arg2_id":"4449","normalized":[]},{"id":"4481","type":"CID","arg1_id":"4450","arg2_id":"4439","normalized":[]},{"id":"4482","type":"CID","arg1_id":"4450","arg2_id":"4441","normalized":[]},{"id":"4483","type":"CID","arg1_id":"4450","arg2_id":"4443","normalized":[]},{"id":"4484","type":"CID","arg1_id":"4450","arg2_id":"4445","normalized":[]},{"id":"4485","type":"CID","arg1_id":"4450","arg2_id":"4447","normalized":[]},{"id":"4486","type":"CID","arg1_id":"4450","arg2_id":"4449","normalized":[]}]}
{"id":"4487","document_id":"19631624","passages":[{"id":"4488","type":"title","text":["Learning and memory deficits in ecstasy users and their neural correlates during a face-learning task."],"offsets":[[0,102]]},{"id":"4489","type":"abstract","text":["It has been consistently shown that ecstasy users display impairments in learning and memory performance. In addition, working memory processing in ecstasy users has been shown to be associated with neural alterations in hippocampal and\/or cortical regions as measured by functional magnetic resonance imaging (fMRI). Using functional imaging and a face-learning task, we investigated neural correlates of encoding and recalling face-name associations in 20 recreational drug users whose predominant drug use was ecstasy and 20 controls. To address the potential confounding effects of the cannabis use of the ecstasy using group, a second analysis included 14 previously tested cannabis users (Nestor, L., Roberts, G., Garavan, H., Hester, R., 2008. Deficits in learning and memory: parahippocampal hyperactivity and frontocortical hypoactivity in cannabis users. Neuroimage 40, 1328-1339). Ecstasy users performed significantly worse in learning and memory compared to controls and cannabis users. A conjunction analysis of the encode and recall phases of the task revealed ecstasy-specific hyperactivity in bilateral frontal regions, left temporal, right parietal, bilateral temporal, and bilateral occipital brain regions. Ecstasy-specific hypoactivity was evident in the right dorsal anterior cingulated cortex (ACC) and left posterior cingulated cortex. In both ecstasy and cannabis groups brain activation was decreased in the right medial frontal gyrus, left parahippocampal gyrus, left dorsal cingulate gyrus, and left caudate. These results elucidated ecstasy-related deficits, only some of which might be attributed to cannabis use. These ecstasy-specific effects may be related to the vulnerability of isocortical and allocortical regions to the neurotoxic effects of ecstasy."],"offsets":[[103,1891]]}],"entities":[{"id":"4490","type":"Disease","text":["Learning and memory deficits"],"offsets":[[0,28]],"normalized":[{"db_name":"MESH","db_id":"D007859"},{"db_name":"MESH","db_id":"D008569"}]},{"id":"4491","type":"Disease","text":["Learning","deficits"],"offsets":[[0,8],[20,28]],"normalized":[{"db_name":"MESH","db_id":"D007859"}]},{"id":"4492","type":"Disease","text":["memory deficits"],"offsets":[[13,28]],"normalized":[{"db_name":"MESH","db_id":"D008569"}]},{"id":"4493","type":"Chemical","text":["ecstasy"],"offsets":[[32,39]],"normalized":[{"db_name":"MESH","db_id":"D018817"}]},{"id":"4494","type":"Chemical","text":["ecstasy"],"offsets":[[139,146]],"normalized":[{"db_name":"MESH","db_id":"D018817"}]},{"id":"4495","type":"Disease","text":["impairments in learning and memory"],"offsets":[[161,195]],"normalized":[{"db_name":"MESH","db_id":"D007859"},{"db_name":"MESH","db_id":"D008569"}]},{"id":"4496","type":"Disease","text":["impairments in learning"],"offsets":[[161,184]],"normalized":[{"db_name":"MESH","db_id":"D007859"}]},{"id":"4497","type":"Disease","text":["impairments 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{"id":"4664","document_id":"20003049","passages":[{"id":"4665","type":"title","text":["Prolonged elevation of plasma argatroban in a cardiac transplant patient with a suspected history of heparin-induced thrombocytopenia with thrombosis."],"offsets":[[0,150]]},{"id":"4666","type":"abstract","text":["BACKGROUND: Direct thrombin inhibitors (DTIs) provide an alternative method of anticoagulation for patients with a history of heparin-induced thrombocytopenia (HIT) or HIT with thrombosis (HITT) undergoing cardiopulmonary bypass (CPB). In the following report, a 65-year-old critically ill patient with a suspected history of HITT was administered argatroban for anticoagulation on bypass during heart transplantation. The patient required massive transfusion support (55 units of red blood cells, 42 units of fresh-frozen plasma, 40 units of cryoprecipitate, 40 units of platelets, and three doses of recombinant Factor VIIa) for severe intraoperative and postoperative bleeding. STUDY DESIGN AND METHODS: Plasma samples from before and after CPB were analyzed postoperatively for argatroban concentration using a modified ecarin clotting time (ECT) assay. RESULTS: Unexpectedly high concentrations of argatroban were measured in these samples (range, 0-32 microg\/mL), and a prolonged plasma argatroban half life (t(1\/2)) of 514 minutes was observed (published elimination t(1\/2) is 39-51 minutes [< or = 181 minutes with hepatic impairment]). CONCLUSIONS: Correlation of plasma argatroban concentration versus the patient's coagulation variables and clinical course suggest that prolonged elevated levels of plasma argatroban may have contributed to the patient's extended coagulopathy. Because DTIs do not have reversal agents, surgical teams and transfusion services should remain aware of the possibility of massive transfusion events during anticoagulation with these agents. This is the first report to measure plasma argatroban concentration in the context of CPB and extended 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impairment"],"offsets":[[1274,1292]],"normalized":[{"db_name":"MESH","db_id":"D008107"}]},{"id":"4687","type":"Chemical","text":["argatroban"],"offsets":[[1331,1341]],"normalized":[{"db_name":"MESH","db_id":"C031942"}]},{"id":"4688","type":"Chemical","text":["argatroban"],"offsets":[[1468,1478]],"normalized":[{"db_name":"MESH","db_id":"C031942"}]},{"id":"4689","type":"Disease","text":["coagulopathy"],"offsets":[[1526,1538]],"normalized":[{"db_name":"MESH","db_id":"D001778"}]},{"id":"4690","type":"Chemical","text":["argatroban"],"offsets":[[1776,1786]],"normalized":[{"db_name":"MESH","db_id":"C031942"}]},{"id":"4691","type":"Disease","text":["coagulopathy"],"offsets":[[1836,1848]],"normalized":[{"db_name":"MESH","db_id":"D001778"}]}],"events":[],"coreferences":[],"relations":[{"id":"4692","type":"CID","arg1_id":"4667","arg2_id":"4680","normalized":[]},{"id":"4693","type":"CID","arg1_id":"4667","arg2_id":"4681","normalized":[]},{"id":"4694","type":"CID","arg1_id":"4679","arg2_id":"4680","normalized":[]},{"id":"4695","type":"CID","arg1_id":"4679","arg2_id":"4681","normalized":[]},{"id":"4696","type":"CID","arg1_id":"4683","arg2_id":"4680","normalized":[]},{"id":"4697","type":"CID","arg1_id":"4683","arg2_id":"4681","normalized":[]},{"id":"4698","type":"CID","arg1_id":"4684","arg2_id":"4680","normalized":[]},{"id":"4699","type":"CID","arg1_id":"4684","arg2_id":"4681","normalized":[]},{"id":"4700","type":"CID","arg1_id":"4685","arg2_id":"4680","normalized":[]},{"id":"4701","type":"CID","arg1_id":"4685","arg2_id":"4681","normalized":[]},{"id":"4702","type":"CID","arg1_id":"4687","arg2_id":"4680","normalized":[]},{"id":"4703","type":"CID","arg1_id":"4687","arg2_id":"4681","normalized":[]},{"id":"4704","type":"CID","arg1_id":"4688","arg2_id":"4680","normalized":[]},{"id":"4705","type":"CID","arg1_id":"4688","arg2_id":"4681","normalized":[]},{"id":"4706","type":"CID","arg1_id":"4690","arg2_id":"4680","normalized":[]},{"id":"4707","type":"CID","arg1_id":"4690","arg2_id":"4681","normalized":[]},{"id":"4708","type":"CID","arg1_id":"4667","arg2_id":"4680","normalized":[]},{"id":"4709","type":"CID","arg1_id":"4667","arg2_id":"4682","normalized":[]},{"id":"4710","type":"CID","arg1_id":"4679","arg2_id":"4680","normalized":[]},{"id":"4711","type":"CID","arg1_id":"4679","arg2_id":"4682","normalized":[]},{"id":"4712","type":"CID","arg1_id":"4683","arg2_id":"4680","normalized":[]},{"id":"4713","type":"CID","arg1_id":"4683","arg2_id":"4682","normalized":[]},{"id":"4714","type":"CID","arg1_id":"4684","arg2_id":"4680","normalized":[]},{"id":"4715","type":"CID","arg1_id":"4684","arg2_id":"4682","normalized":[]},{"id":"4716","type":"CID","arg1_id":"4685","arg2_id":"4680","normalized":[]},{"id":"4717","type":"CID","arg1_id":"4685","arg2_id":"4682","normalized":[]},{"id":"4718","type":"CID","arg1_id":"4687","arg2_id":"4680","normalized":[]},{"id":"4719","type":"CID","arg1_id":"4687","arg2_id":"4682","normalized":[]},{"id":"4720","type":"CID","arg1_id":"4688","arg2_id":"4680","normalized":[]},{"id":"4721","type":"CID","arg1_id":"4688","arg2_id":"4682","normalized":[]},{"id":"4722","type":"CID","arg1_id":"4690","arg2_id":"4680","normalized":[]},{"id":"4723","type":"CID","arg1_id":"4690","arg2_id":"4682","normalized":[]}]}
{"id":"4724","document_id":"20196116","passages":[{"id":"4725","type":"title","text":["Antituberculosis therapy-induced acute liver failure: magnitude, profile, prognosis, and predictors of outcome."],"offsets":[[0,111]]},{"id":"4726","type":"abstract","text":["Antituberculosis therapy (ATT)-associated acute liver failure (ATT-ALF) is the commonest drug-induced ALF in South Asia. Prospective studies on ATT-ALF are lacking. The current study prospectively evaluated the magnitude, clinical course, outcome, and prognostic factors in ATT-ALF. From January 1986 to January 2009, 1223 consecutive ALF patients were evaluated: ATT alone was the cause in 70 (5.7%) patients. Another 15 (1.2%) had ATT and simultaneous hepatitis virus infection. In 44 (62.8%) patients, ATT was prescribed empirically without definitive evidence of tuberculosis. ATT-ALF patients were younger (32.87 [+\/-15.8] years), and 49 (70%) of them were women. Most had hyperacute presentation; the median icterus encephalopathy interval was 4.5 (0-30) days. The median duration of ATT before ALF was 30 (7-350) days. At presentation, advanced encephalopathy and cerebral edema were present in 51 (76%) and 29 (41.4%) patients, respectively. Gastrointestinal bleed, seizures, infection, and acute renal failure were documented in seven (10%), five (7.1%), 26 (37.1%), and seven (10%) patients, respectively. Compared with hepatitis E virus (HEV) and non-A non-E-induced ALF, ATT-ALF patients had nearly similar presentations except for older age and less elevation of liver enzymes. The mortality rate among patients with ATT-ALF was high (67.1%, n = 47), and only 23 (32.9%) patients recovered with medical treatment. In multivariate analysis, three factors independently predicted mortality: serum bilirubin (>or=10.8 mg\/dL), prothrombin time (PT) prolongation (>or=26 seconds), and grade III\/IV encephalopathy at presentation. CONCLUSION: ATT-ALF constituted 5.7% of ALF at our center and had a high mortality rate. Because the mortality rate is so high, determining which factors are predictors is less important. A high proportion of patients had consumed ATT empirically, which could have been prevented."],"offsets":[[112,2030]]}],"entities":[{"id":"4727","type":"Chemical","text":["Antituberculosis"],"offsets":[[0,16]],"normalized":[{"db_name":"MESH","db_id":"D000995"}]},{"id":"4728","type":"Disease","text":["acute liver failure"],"offsets":[[33,52]],"normalized":[{"db_name":"MESH","db_id":"D017114"}]},{"id":"4729","type":"Chemical","text":["Antituberculosis"],"offsets":[[112,128]],"normalized":[{"db_name":"MESH","db_id":"D000995"}]},{"id":"4730","type":"Disease","text":["acute liver 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edema"],"offsets":[[983,997]],"normalized":[{"db_name":"MESH","db_id":"D001929"}]},{"id":"4744","type":"Disease","text":["Gastrointestinal bleed"],"offsets":[[1062,1084]],"normalized":[{"db_name":"MESH","db_id":"D006471"}]},{"id":"4745","type":"Disease","text":["seizures"],"offsets":[[1086,1094]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"4746","type":"Disease","text":["infection"],"offsets":[[1096,1105]],"normalized":[{"db_name":"MESH","db_id":"D007239"}]},{"id":"4747","type":"Disease","text":["acute renal failure"],"offsets":[[1111,1130]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"4748","type":"Disease","text":["hepatitis 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{"id":"4784","document_id":"20470218","passages":[{"id":"4785","type":"title","text":["Central nervous system complications during treatment of acute lymphoblastic leukemia in a single pediatric institution."],"offsets":[[0,120]]},{"id":"4786","type":"abstract","text":["Central nervous system (CNS) complications during treatment of childhood acute lymphoblastic leukemia (ALL) remain a challenging clinical problem. Outcome improvement with more intensive chemotherapy has significantly increased the incidence and severity of adverse events. This study analyzed the incidence of neurological complications during ALL treatment in a single pediatric institution, focusing on clinical, radiological, and electrophysiological findings. Exclusion criteria included CNS leukemic infiltration at diagnosis, therapy-related peripheral neuropathy, late-onset encephalopathy, or long-term neurocognitive defects. During a 9-year period, we retrospectively collected 27 neurological events (11%) in as many patients, from 253 children enrolled in the ALL front-line protocol. CNS complications included posterior reversible leukoencephalopathy syndrome (n = 10), stroke (n = 5), temporal lobe epilepsy (n = 2), high-dose methotrexate toxicity (n = 2), syndrome of inappropriate antidiuretic hormone secretion (n = 1), and other unclassified events (n = 7). In conclusion, CNS complications are frequent events during ALL therapy, and require rapid detection and prompt treatment to limit permanent damage."],"offsets":[[121,1348]]}],"entities":[{"id":"4787","type":"Disease","text":["Central nervous system complications"],"offsets":[[0,36]],"normalized":[{"db_name":"MESH","db_id":"D002493"}]},{"id":"4788","type":"Disease","text":["acute lymphoblastic leukemia"],"offsets":[[57,85]],"normalized":[{"db_name":"MESH","db_id":"D054198"}]},{"id":"4789","type":"Disease","text":["Central nervous system (CNS) complications"],"offsets":[[121,163]],"normalized":[{"db_name":"MESH","db_id":"D002493"}]},{"id":"4790","type":"Disease","text":["acute lymphoblastic leukemia"],"offsets":[[194,222]],"normalized":[{"db_name":"MESH","db_id":"D054198"}]},{"id":"4791","type":"Disease","text":["ALL"],"offsets":[[224,227]],"normalized":[{"db_name":"MESH","db_id":"D054198"}]},{"id":"4792","type":"Disease","text":["neurological complications"],"offsets":[[432,458]],"normalized":[{"db_name":"MESH","db_id":"D002493"}]},{"id":"4793","type":"Disease","text":["ALL"],"offsets":[[466,469]],"normalized":[{"db_name":"MESH","db_id":"D054198"}]},{"id":"4794","type":"Disease","text":["leukemic infiltration"],"offsets":[[618,639]],"normalized":[{"db_name":"MESH","db_id":"D017254"}]},{"id":"4795","type":"Disease","text":["peripheral neuropathy"],"offsets":[[670,691]],"normalized":[{"db_name":"MESH","db_id":"D010523"}]},{"id":"4796","type":"Disease","text":["encephalopathy"],"offsets":[[704,718]],"normalized":[{"db_name":"MESH","db_id":"D001927"}]},{"id":"4797","type":"Disease","text":["neurocognitive defects"],"offsets":[[733,755]],"normalized":[{"db_name":"MESH","db_id":"D002493"}]},{"id":"4798","type":"Disease","text":["ALL"],"offsets":[[894,897]],"normalized":[{"db_name":"MESH","db_id":"D054198"}]},{"id":"4799","type":"Disease","text":["leukoencephalopathy"],"offsets":[[967,986]],"normalized":[{"db_name":"MESH","db_id":"D056784"}]},{"id":"4800","type":"Disease","text":["stroke"],"offsets":[[1006,1012]],"normalized":[{"db_name":"MESH","db_id":"D020521"}]},{"id":"4801","type":"Disease","text":["temporal lobe epilepsy"],"offsets":[[1022,1044]],"normalized":[{"db_name":"MESH","db_id":"D004833"}]},{"id":"4802","type":"Chemical","text":["methotrexate"],"offsets":[[1064,1076]],"normalized":[{"db_name":"MESH","db_id":"D008727"}]},{"id":"4803","type":"Disease","text":["toxicity"],"offsets":[[1077,1085]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"4804","type":"Disease","text":["inappropriate antidiuretic hormone secretion"],"offsets":[[1107,1151]],"normalized":[{"db_name":"MESH","db_id":"D007177"}]},{"id":"4805","type":"Disease","text":["ALL"],"offsets":[[1260,1263]],"normalized":[{"db_name":"MESH","db_id":"D054198"}]}],"events":[],"coreferences":[],"relations":[{"id":"4806","type":"CID","arg1_id":"4802","arg2_id":"4787","normalized":[]},{"id":"4807","type":"CID","arg1_id":"4802","arg2_id":"4789","normalized":[]},{"id":"4808","type":"CID","arg1_id":"4802","arg2_id":"4792","normalized":[]},{"id":"4809","type":"CID","arg1_id":"4802","arg2_id":"4797","normalized":[]}]}
{"id":"4810","document_id":"20722491","passages":[{"id":"4811","type":"title","text":["Safety of capecitabine: a review."],"offsets":[[0,33]]},{"id":"4812","type":"abstract","text":["IMPORTANCE OF THE FIELD: Fluoropyrimidines, in particular 5-fluorouracil (5-FU), have been the mainstay of treatment for several solid tumors, including colorectal, breast and head and neck cancers, for > 40 years. AREAS COVERED IN THIS REVIEW: This article reviews the pharmacology and efficacy of capecitabine with a special emphasis on its safety. WHAT THE READER WILL GAIN: The reader will gain better insight into the safety of capecitabine in special populations such as patients with advanced age, renal and kidney disease. We also explore different dosing and schedules of capecitabine administration. TAKE HOME MESSAGE: Capecitabine is an oral prodrug of 5-FU and was developed to fulfill the need for a more convenient therapy and provide an improved safety\/efficacy profile. It has shown promising results alone or in combination with other chemotherapeutic agents in colorectal, breast, pancreaticobiliary, gastric, renal cell and head and neck cancers. The most commonly reported toxic effects of capecitabine are diarrhea, nausea, vomiting, stomatitis and hand-foot syndrome. Capecitabine has a well-established safety profile and can be given safely to patients with advanced age, hepatic and renal dysfunctions."],"offsets":[[34,1261]]}],"entities":[{"id":"4813","type":"Chemical","text":["capecitabine"],"offsets":[[10,22]],"normalized":[{"db_name":"MESH","db_id":"C110904"}]},{"id":"4814","type":"Chemical","text":["Fluoropyrimidines"],"offsets":[[59,76]],"normalized":[]},{"id":"4815","type":"Chemical","text":["5-fluorouracil"],"offsets":[[92,106]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"4816","type":"Chemical","text":["5-FU"],"offsets":[[108,112]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"4817","type":"Disease","text":["tumors"],"offsets":[[169,175]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"4818","type":"Disease","text":["colorectal, breast and head and neck 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disease"],"offsets":[[539,563]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"4825","type":"Chemical","text":["capecitabine"],"offsets":[[615,627]],"normalized":[{"db_name":"MESH","db_id":"C110904"}]},{"id":"4826","type":"Chemical","text":["Capecitabine"],"offsets":[[663,675]],"normalized":[{"db_name":"MESH","db_id":"C110904"}]},{"id":"4827","type":"Chemical","text":["5-FU"],"offsets":[[698,702]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"4828","type":"Disease","text":["colorectal, breast, pancreaticobiliary, gastric, renal cell and head and neck 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syndrome"],"offsets":[[1104,1122]],"normalized":[{"db_name":"MESH","db_id":"D060831"}]},{"id":"4841","type":"Chemical","text":["Capecitabine"],"offsets":[[1124,1136]],"normalized":[{"db_name":"MESH","db_id":"C110904"}]},{"id":"4842","type":"Disease","text":["hepatic and renal dysfunctions"],"offsets":[[1230,1260]],"normalized":[{"db_name":"MESH","db_id":"D008107"},{"db_name":"MESH","db_id":"D007674"}]},{"id":"4843","type":"Disease","text":["hepatic","dysfunctions"],"offsets":[[1230,1237],[1248,1260]],"normalized":[{"db_name":"MESH","db_id":"D008107"}]},{"id":"4844","type":"Disease","text":["renal dysfunctions"],"offsets":[[1242,1260]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]}],"events":[],"coreferences":[],"relations":[{"id":"4845","type":"CID","arg1_id":"4813","arg2_id":"4840","normalized":[]},{"id":"4846","type":"CID","arg1_id":"4822","arg2_id":"4840","normalized":[]},{"id":"4847","type":"CID","arg1_id":"4823","arg2_id":"4840","normalized":[]},{"id":"4848","type":"CID","arg1_id":"4825","arg2_id":"4840","normalized":[]},{"id":"4849","type":"CID","arg1_id":"4826","arg2_id":"4840","normalized":[]},{"id":"4850","type":"CID","arg1_id":"4835","arg2_id":"4840","normalized":[]},{"id":"4851","type":"CID","arg1_id":"4841","arg2_id":"4840","normalized":[]},{"id":"4852","type":"CID","arg1_id":"4813","arg2_id":"4839","normalized":[]},{"id":"4853","type":"CID","arg1_id":"4822","arg2_id":"4839","normalized":[]},{"id":"4854","type":"CID","arg1_id":"4823","arg2_id":"4839","normalized":[]},{"id":"4855","type":"CID","arg1_id":"4825","arg2_id":"4839","normalized":[]},{"id":"4856","type":"CID","arg1_id":"4826","arg2_id":"4839","normalized":[]},{"id":"4857","type":"CID","arg1_id":"4835","arg2_id":"4839","normalized":[]},{"id":"4858","type":"CID","arg1_id":"4841","arg2_id":"4839","normalized":[]},{"id":"4859","type":"CID","arg1_id":"4813","arg2_id":"4838","normalized":[]},{"id":"4860","type":"CID","arg1_id":"4822","arg2_id":"4838","normalized":[]},{"id":"4861","type":"CID","arg1_id":"4823","arg2_id":"4838","normalized":[]},{"id":"4862","type":"CID","arg1_id":"4825","arg2_id":"4838","normalized":[]},{"id":"4863","type":"CID","arg1_id":"4826","arg2_id":"4838","normalized":[]},{"id":"4864","type":"CID","arg1_id":"4835","arg2_id":"4838","normalized":[]},{"id":"4865","type":"CID","arg1_id":"4841","arg2_id":"4838","normalized":[]},{"id":"4866","type":"CID","arg1_id":"4813","arg2_id":"4836","normalized":[]},{"id":"4867","type":"CID","arg1_id":"4822","arg2_id":"4836","normalized":[]},{"id":"4868","type":"CID","arg1_id":"4823","arg2_id":"4836","normalized":[]},{"id":"4869","type":"CID","arg1_id":"4825","arg2_id":"4836","normalized":[]},{"id":"4870","type":"CID","arg1_id":"4826","arg2_id":"4836","normalized":[]},{"id":"4871","type":"CID","arg1_id":"4835","arg2_id":"4836","normalized":[]},{"id":"4872","type":"CID","arg1_id":"4841","arg2_id":"4836","normalized":[]},{"id":"4873","type":"CID","arg1_id":"4813","arg2_id":"4837","normalized":[]},{"id":"4874","type":"CID","arg1_id":"4822","arg2_id":"4837","normalized":[]},{"id":"4875","type":"CID","arg1_id":"4823","arg2_id":"4837","normalized":[]},{"id":"4876","type":"CID","arg1_id":"4825","arg2_id":"4837","normalized":[]},{"id":"4877","type":"CID","arg1_id":"4826","arg2_id":"4837","normalized":[]},{"id":"4878","type":"CID","arg1_id":"4835","arg2_id":"4837","normalized":[]},{"id":"4879","type":"CID","arg1_id":"4841","arg2_id":"4837","normalized":[]}]}
{"id":"4880","document_id":"20882060","passages":[{"id":"4881","type":"title","text":["Effects of pallidal neurotensin on haloperidol-induced parkinsonian catalepsy: behavioral and electrophysiological studies."],"offsets":[[0,123]]},{"id":"4882","type":"abstract","text":["OBJECTIVE: The globus pallidus plays a critical role in movement regulation. Previous studies have indicated that the globus pallidus receives neurotensinergic innervation from the striatum, and systemic administration of a neurotensin analog could produce antiparkinsonian effects. The present study aimed to investigate the effects of pallidal neurotensin on haloperidol-induced parkinsonian symptoms. METHODS: Behavioral experiments and electrophysiological recordings were performed in the present study. RESULTS: Bilateral infusions of neurotensin into the globus pallidus reversed haloperidol-induced parkinsonian catalepsy in rats. Electrophysiological recordings showed that microinjection of neurotensin induced excitation of pallidal neurons in the presence of systemic haloperidol administration. The neurotensin type-1 receptor antagonist SR48692 blocked both the behavioral and the electrophysiological effects induced by neurotensin. CONCLUSION: Activation of pallidal neurotensin receptors may be involved in neurotensin-induced antiparkinsonian effects."],"offsets":[[124,1193]]}],"entities":[{"id":"4883","type":"Chemical","text":["neurotensin"],"offsets":[[20,31]],"normalized":[{"db_name":"MESH","db_id":"D009496"}]},{"id":"4884","type":"Chemical","text":["haloperidol"],"offsets":[[35,46]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"4885","type":"Disease","text":["parkinsonian catalepsy"],"offsets":[[55,77]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"4886","type":"Chemical","text":["neurotensin"],"offsets":[[348,359]],"normalized":[{"db_name":"MESH","db_id":"D009496"}]},{"id":"4887","type":"Chemical","text":["neurotensin"],"offsets":[[470,481]],"normalized":[{"db_name":"MESH","db_id":"D009496"}]},{"id":"4888","type":"Chemical","text":["haloperidol"],"offsets":[[485,496]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"4889","type":"Disease","text":["parkinsonian symptoms"],"offsets":[[505,526]],"normalized":[{"db_name":"MESH","db_id":"D010302"}]},{"id":"4890","type":"Chemical","text":["neurotensin"],"offsets":[[665,676]],"normalized":[{"db_name":"MESH","db_id":"D009496"}]},{"id":"4891","type":"Chemical","text":["haloperidol"],"offsets":[[711,722]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"4892","type":"Disease","text":["parkinsonian catalepsy"],"offsets":[[731,753]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"4893","type":"Chemical","text":["neurotensin"],"offsets":[[825,836]],"normalized":[{"db_name":"MESH","db_id":"D009496"}]},{"id":"4894","type":"Chemical","text":["haloperidol"],"offsets":[[904,915]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"4895","type":"Chemical","text":["neurotensin type-1 receptor antagonist"],"offsets":[[936,974]],"normalized":[{"db_name":"MESH","db_id":"C079087"}]},{"id":"4896","type":"Chemical","text":["SR48692"],"offsets":[[975,982]],"normalized":[{"db_name":"MESH","db_id":"C079087"}]},{"id":"4897","type":"Chemical","text":["neurotensin"],"offsets":[[1059,1070]],"normalized":[{"db_name":"MESH","db_id":"D009496"}]},{"id":"4898","type":"Chemical","text":["neurotensin"],"offsets":[[1107,1118]],"normalized":[{"db_name":"MESH","db_id":"D009496"}]},{"id":"4899","type":"Chemical","text":["neurotensin"],"offsets":[[1148,1159]],"normalized":[{"db_name":"MESH","db_id":"D009496"}]}],"events":[],"coreferences":[],"relations":[{"id":"4900","type":"CID","arg1_id":"4884","arg2_id":"4885","normalized":[]},{"id":"4901","type":"CID","arg1_id":"4884","arg2_id":"4892","normalized":[]},{"id":"4902","type":"CID","arg1_id":"4888","arg2_id":"4885","normalized":[]},{"id":"4903","type":"CID","arg1_id":"4888","arg2_id":"4892","normalized":[]},{"id":"4904","type":"CID","arg1_id":"4891","arg2_id":"4885","normalized":[]},{"id":"4905","type":"CID","arg1_id":"4891","arg2_id":"4892","normalized":[]},{"id":"4906","type":"CID","arg1_id":"4894","arg2_id":"4885","normalized":[]},{"id":"4907","type":"CID","arg1_id":"4894","arg2_id":"4892","normalized":[]}]}
{"id":"4908","document_id":"26094","passages":[{"id":"4909","type":"title","text":["Antihypertensive drugs and depression: a reappraisal."],"offsets":[[0,53]]},{"id":"4910","type":"abstract","text":["Eighty-nine new referral hypertensive out-patients and 46 new referral non-hypertensive chronically physically ill out-patients completed a mood rating scale at regular intervals for one year. The results showed a high prevalence of depression in both groups of patients, with no preponderance in the hypertensive group. Hypertensive patients with psychiatric histories had a higher prevalence of depression than the comparison patients. This was accounted for by a significant number of depressions occurring in methyl dopa treated patients with psychiatric histories."],"offsets":[[54,623]]}],"entities":[{"id":"4911","type":"Disease","text":["depression"],"offsets":[[27,37]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"4912","type":"Disease","text":["hypertensive"],"offsets":[[79,91]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"4913","type":"Disease","text":["hypertensive"],"offsets":[[129,141]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"4914","type":"Disease","text":["depression"],"offsets":[[287,297]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"4915","type":"Disease","text":["hypertensive"],"offsets":[[355,367]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"4916","type":"Disease","text":["Hypertensive"],"offsets":[[375,387]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"4917","type":"Disease","text":["psychiatric"],"offsets":[[402,413]],"normalized":[{"db_name":"MESH","db_id":"D001523"}]},{"id":"4918","type":"Disease","text":["depression"],"offsets":[[451,461]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"4919","type":"Disease","text":["depressions"],"offsets":[[542,553]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"4920","type":"Chemical","text":["methyl dopa"],"offsets":[[567,578]],"normalized":[{"db_name":"MESH","db_id":"D008750"}]},{"id":"4921","type":"Disease","text":["psychiatric"],"offsets":[[601,612]],"normalized":[{"db_name":"MESH","db_id":"D001523"}]}],"events":[],"coreferences":[],"relations":[{"id":"4922","type":"CID","arg1_id":"4920","arg2_id":"4911","normalized":[]},{"id":"4923","type":"CID","arg1_id":"4920","arg2_id":"4914","normalized":[]},{"id":"4924","type":"CID","arg1_id":"4920","arg2_id":"4918","normalized":[]},{"id":"4925","type":"CID","arg1_id":"4920","arg2_id":"4919","normalized":[]}]}
{"id":"4926","document_id":"322550","passages":[{"id":"4927","type":"title","text":["Pulmonary shunt and cardiovascular responses to CPAP during nitroprusside-induced hypotension."],"offsets":[[0,94]]},{"id":"4928","type":"abstract","text":["The effects of continuous positive airway pressure (CPAP) on cardiovascular dynamics and pulmonary shunt (QS\/QT) were investigated in 12 dogs before and during sodium nitroprusside infusion that decreased mean arterial blood pressure 40-50 per cent. Before nitroprusside infusion, 5 cm H2O CPAP significantly, P less than .05, decreased arterial blood pressure, but did not significantly alter heart rate, cardiac output, systemic vascular resistance, or QS\/QT. Ten cm H2O CPAP before nitroprusside infusion produced a further decrease in arterial blood pressure and significantly increased heart rate and decreased cardiac output and QS\/QT. Nitroprusside caused significant decreases in arterial blood pressure and systemic vascular resistance and increases in heart rate, but did not change cardiac output or QS\/QT. Five cm H2O CPAP during nitroprusside did not further alter any of the above-mentioned variables. However, 10 cm H2O CPAP decreased arterial blood pressure, cardiac output, and QS\/QT. These data indicate that nitroprusside infusion rates that decrease mean arterial blood pressure by 40-50 per cent do not change cardiac output or QS\/QT. During nitroprusside infusion low levels of CPAP do not markedly alter cardiovascular dynamics, but high levels of CPAP (10 cm H2O), while decreasing QS\/QT, produce marked decreases in arterial blood pressure and cardiac output."],"offsets":[[95,1479]]}],"entities":[{"id":"4929","type":"Chemical","text":["nitroprusside"],"offsets":[[60,73]],"normalized":[{"db_name":"MESH","db_id":"D009599"}]},{"id":"4930","type":"Disease","text":["hypotension"],"offsets":[[82,93]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"4931","type":"Chemical","text":["sodium 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output"],"offsets":[[701,725]],"normalized":[{"db_name":"MESH","db_id":"D002303"}]},{"id":"4938","type":"Chemical","text":["Nitroprusside"],"offsets":[[737,750]],"normalized":[{"db_name":"MESH","db_id":"D009599"}]},{"id":"4939","type":"Disease","text":["decreases in arterial blood pressure"],"offsets":[[770,806]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"4940","type":"Chemical","text":["H2O"],"offsets":[[921,924]],"normalized":[{"db_name":"MESH","db_id":"D014867"}]},{"id":"4941","type":"Chemical","text":["nitroprusside"],"offsets":[[937,950]],"normalized":[{"db_name":"MESH","db_id":"D009599"}]},{"id":"4942","type":"Chemical","text":["H2O"],"offsets":[[1026,1029]],"normalized":[{"db_name":"MESH","db_id":"D014867"}]},{"id":"4943","type":"Chemical","text":["nitroprusside"],"offsets":[[1122,1135]],"normalized":[{"db_name":"MESH","db_id":"D009599"}]},{"id":"4944","type":"Chemical","text":["nitroprusside"],"offsets":[[1258,1271]],"normalized":[{"db_name":"MESH","db_id":"D009599"}]},{"id":"4945","type":"Chemical","text":["H2O"],"offsets":[[1378,1381]],"normalized":[{"db_name":"MESH","db_id":"D014867"}]},{"id":"4946","type":"Disease","text":["decreases in arterial blood pressure and cardiac output"],"offsets":[[1423,1478]],"normalized":[{"db_name":"MESH","db_id":"D007022"},{"db_name":"MESH","db_id":"D002303"}]},{"id":"4947","type":"Disease","text":["decreases in arterial blood pressure"],"offsets":[[1423,1459]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"4948","type":"Disease","text":["decreases in","cardiac 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{"id":"4989","document_id":"869641","passages":[{"id":"4990","type":"title","text":["Mediation of enhanced reflex vagal bradycardia by L-dopa via central dopamine formation in dogs."],"offsets":[[0,96]]},{"id":"4991","type":"abstract","text":["L-Dopa (5 mg\/kg i.v.) decreased blood pressure and heart rate after extracerebral decarboxylase inhibition with MK-486 (25 mg\/kg i.v.) in anesthetize MAO-inhibited dogs. In addition, reflex bradycardia caused by injected norepinephrine was significantly enhanced by L-dopa, DL-Threo-dihydroxyphenylserine had no effect on blood pressure, heart rate or reflex responses to norepinephrine. FLA-63, a dopamine-beta-oxidase inhibitor, did not have any effect on the hypotension, bradycardia or reflex-enhancing effect of L-dopa. Pimozide did not affect the actions of L-dopa on blood pressure and heart rate but completely blocked the enhancement of reflexes. Removal of the carotid sinuses caused an elevation blood pressure and heart rate and abolished the negative chronotropic effect of norepinephrine. However, L-dopa restored the bradycardia caused by norepinephrine in addition to decreasing blood pressure and heart rate. 5-HTP (5 mg\/kg i.v.) decreased blood pressure and heart rate and decreased the reflex bradycardia to norepinephrine. It is concluded that L-dopa enhances reflex bradycardia through central alpha-receptor stimulation. Furthermore, the effects are mediated through dopamine rather than norepinephrine and do not require the carotid sinus baroreceptors."],"offsets":[[97,1373]]}],"entities":[{"id":"4992","type":"Disease","text":["bradycardia"],"offsets":[[35,46]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"4993","type":"Chemical","text":["L-dopa"],"offsets":[[50,56]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"4994","type":"Chemical","text":["dopamine"],"offsets":[[69,77]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"4995","type":"Chemical","text":["L-Dopa"],"offsets":[[97,103]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"4996","type":"Chemical","text":["MK-486"],"offsets":[[209,215]],"normalized":[{"db_name":"MESH","db_id":"D002230"}]},{"id":"4997","type":"Chemical","text":["MAO"],"offsets":[[247,250]],"normalized":[{"db_name":"MESH","db_id":"D008995"}]},{"id":"4998","type":"Disease","text":["bradycardia"],"offsets":[[287,298]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"4999","type":"Chemical","text":["norepinephrine"],"offsets":[[318,332]],"normalized":[{"db_name":"MESH","db_id":"D009638"}]},{"id":"5000","type":"Chemical","text":["L-dopa"],"offsets":[[363,369]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"5001","type":"Chemical","text":["DL-Threo-dihydroxyphenylserine"],"offsets":[[371,401]],"normalized":[{"db_name":"MESH","db_id":"D015103"}]},{"id":"5002","type":"Chemical","text":["norepinephrine"],"offsets":[[469,483]],"normalized":[{"db_name":"MESH","db_id":"D009638"}]},{"id":"5003","type":"Chemical","text":["FLA-63"],"offsets":[[485,491]],"normalized":[{"db_name":"MESH","db_id":"D005406"}]},{"id":"5004","type":"Chemical","text":["dopamine"],"offsets":[[495,503]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"5005","type":"Disease","text":["hypotension"],"offsets":[[559,570]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"5006","type":"Disease","text":["bradycardia"],"offsets":[[572,583]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"5007","type":"Chemical","text":["L-dopa"],"offsets":[[614,620]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"5008","type":"Chemical","text":["Pimozide"],"offsets":[[622,630]],"normalized":[{"db_name":"MESH","db_id":"D010868"}]},{"id":"5009","type":"Chemical","text":["L-dopa"],"offsets":[[661,667]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"5010","type":"Chemical","text":["norepinephrine"],"offsets":[[884,898]],"normalized":[{"db_name":"MESH","db_id":"D009638"}]},{"id":"5011","type":"Chemical","text":["L-dopa"],"offsets":[[909,915]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"5012","type":"Disease","text":["bradycardia"],"offsets":[[929,940]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"5013","type":"Chemical","text":["norepinephrine"],"offsets":[[951,965]],"normalized":[{"db_name":"MESH","db_id":"D009638"}]},{"id":"5014","type":"Chemical","text":["5-HTP"],"offsets":[[1023,1028]],"normalized":[{"db_name":"MESH","db_id":"D006916"}]},{"id":"5015","type":"Disease","text":["bradycardia"],"offsets":[[1109,1120]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"5016","type":"Chemical","text":["norepinephrine"],"offsets":[[1124,1138]],"normalized":[{"db_name":"MESH","db_id":"D009638"}]},{"id":"5017","type":"Chemical","text":["L-dopa"],"offsets":[[1161,1167]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"5018","type":"Disease","text":["bradycardia"],"offsets":[[1184,1195]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"5019","type":"Chemical","text":["dopamine"],"offsets":[[1286,1294]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"5020","type":"Chemical","text":["norepinephrine"],"offsets":[[1307,1321]],"normalized":[{"db_name":"MESH","db_id":"D009638"}]}],"events":[],"coreferences":[],"relations":[{"id":"5021","type":"CID","arg1_id":"4999","arg2_id":"4992","normalized":[]},{"id":"5022","type":"CID","arg1_id":"4999","arg2_id":"4998","normalized":[]},{"id":"5023","type":"CID","arg1_id":"4999","arg2_id":"5006","normalized":[]},{"id":"5024","type":"CID","arg1_id":"4999","arg2_id":"5012","normalized":[]},{"id":"5025","type":"CID","arg1_id":"4999","arg2_id":"5015","normalized":[]},{"id":"5026","type":"CID","arg1_id":"4999","arg2_id":"5018","normalized":[]},{"id":"5027","type":"CID","arg1_id":"5002","arg2_id":"4992","normalized":[]},{"id":"5028","type":"CID","arg1_id":"5002","arg2_id":"4998","normalized":[]},{"id":"5029","type":"CID","arg1_id":"5002","arg2_id":"5006","normalized":[]},{"id":"5030","type":"CID","arg1_id":"5002","arg2_id":"5012","normalized":[]},{"id":"5031","type":"CID","arg1_id":"5002","arg2_id":"5015","normalized":[]},{"id":"5032","type":"CID","arg1_id":"5002","arg2_id":"5018","normalized":[]},{"id":"5033","type":"CID","arg1_id":"5010","arg2_id":"4992","normalized":[]},{"id":"5034","type":"CID","arg1_id":"5010","arg2_id":"4998","normalized":[]},{"id":"5035","type":"CID","arg1_id":"5010","arg2_id":"5006","normalized":[]},{"id":"5036","type":"CID","arg1_id":"5010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{"id":"5057","document_id":"1749407","passages":[{"id":"5058","type":"title","text":["Cocaine-induced myocardial infarction: clinical observations and pathogenetic considerations."],"offsets":[[0,93]]},{"id":"5059","type":"abstract","text":["Clinical and experimental data published to date suggest several possible mechanisms by which cocaine may result in acute myocardial infarction. In individuals with preexisting, high-grade coronary arterial narrowing, acute myocardial infarction may result from an increase in myocardial oxygen demand associated with cocaine-induced increase in rate-pressure product. In other individuals with no underlying atherosclerotic obstruction, coronary occlusion may be due to spasm, thrombus, or both. With regard to spasm, the clinical findings are largely circumstantial, and the locus of cocaine-induced vasoconstriction remains speculative. Although certain clinical and experimental findings support the hypothesis that spasm involves the epicardial, medium-size vessels, other data suggest intramural vasoconstriction. Diffuse intramural vasoconstriction is not consistent with reports of segmental, discrete infarction. Whereas certain in vivo data suggest that these effects are alpha-mediated, other in vitro data suggest the opposite. The finding of cocaine-induced vasoconstriction in segments of (noninnervated) human umbilical artery suggests that the presence or absence of intact innervation is not sufficient to explain the discrepant data involving the possibility of alpha-mediated effects. Finally, the contribution of a primary, thrombotic effect of cocaine has not been excluded."],"offsets":[[94,1489]]}],"entities":[{"id":"5060","type":"Chemical","text":["Cocaine"],"offsets":[[0,7]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"5061","type":"Disease","text":["myocardial infarction"],"offsets":[[16,37]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"5062","type":"Chemical","text":["cocaine"],"offsets":[[188,195]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"5063","type":"Disease","text":["acute myocardial infarction"],"offsets":[[210,237]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"5064","type":"Disease","text":["acute myocardial infarction"],"offsets":[[312,339]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"5065","type":"Chemical","text":["oxygen"],"offsets":[[382,388]],"normalized":[{"db_name":"MESH","db_id":"D010100"}]},{"id":"5066","type":"Chemical","text":["cocaine"],"offsets":[[412,419]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"5067","type":"Disease","text":["atherosclerotic obstruction"],"offsets":[[503,530]],"normalized":[{"db_name":"MESH","db_id":"D050197"}]},{"id":"5068","type":"Disease","text":["coronary occlusion"],"offsets":[[532,550]],"normalized":[{"db_name":"MESH","db_id":"D054059"}]},{"id":"5069","type":"Disease","text":["spasm"],"offsets":[[565,570]],"normalized":[{"db_name":"MESH","db_id":"D013035"}]},{"id":"5070","type":"Disease","text":["thrombus"],"offsets":[[572,580]],"normalized":[{"db_name":"MESH","db_id":"D013927"}]},{"id":"5071","type":"Disease","text":["spasm"],"offsets":[[606,611]],"normalized":[{"db_name":"MESH","db_id":"D013035"}]},{"id":"5072","type":"Chemical","text":["cocaine"],"offsets":[[680,687]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"5073","type":"Disease","text":["spasm"],"offsets":[[814,819]],"normalized":[{"db_name":"MESH","db_id":"D013035"}]},{"id":"5074","type":"Disease","text":["infarction"],"offsets":[[1004,1014]],"normalized":[{"db_name":"MESH","db_id":"D007238"}]},{"id":"5075","type":"Chemical","text":["cocaine"],"offsets":[[1149,1156]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"5076","type":"Disease","text":["thrombotic"],"offsets":[[1438,1448]],"normalized":[{"db_name":"MESH","db_id":"D013927"}]},{"id":"5077","type":"Chemical","text":["cocaine"],"offsets":[[1459,1466]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]}],"events":[],"coreferences":[],"relations":[{"id":"5078","type":"CID","arg1_id":"5060","arg2_id":"5061","normalized":[]},{"id":"5079","type":"CID","arg1_id":"5060","arg2_id":"5063","normalized":[]},{"id":"5080","type":"CID","arg1_id":"5060","arg2_id":"5064","normalized":[]},{"id":"5081","type":"CID","arg1_id":"5062","arg2_id":"5061","normalized":[]},{"id":"5082","type":"CID","arg1_id":"5062","arg2_id":"5063","normalized":[]},{"id":"5083","type":"CID","arg1_id":"5062","arg2_id":"5064","normalized":[]},{"id":"5084","type":"CID","arg1_id":"5066","arg2_id":"5061","normalized":[]},{"id":"5085","type":"CID","arg1_id":"5066","arg2_id":"5063","normalized":[]},{"id":"5086","type":"CID","arg1_id":"5066","arg2_id":"5064","normalized":[]},{"id":"5087","type":"CID","arg1_id":"5072","arg2_id":"5061","normalized":[]},{"id":"5088","type":"CID","arg1_id":"5072","arg2_id":"5063","normalized":[]},{"id":"5089","type":"CID","arg1_id":"5072","arg2_id":"5064","normalized":[]},{"id":"5090","type":"CID","arg1_id":"5075","arg2_id":"5061","normalized":[]},{"id":"5091","type":"CID","arg1_id":"5075","arg2_id":"5063","normalized":[]},{"id":"5092","type":"CID","arg1_id":"5075","arg2_id":"5064","normalized":[]},{"id":"5093","type":"CID","arg1_id":"5077","arg2_id":"5061","normalized":[]},{"id":"5094","type":"CID","arg1_id":"5077","arg2_id":"5063","normalized":[]},{"id":"5095","type":"CID","arg1_id":"5077","arg2_id":"5064","normalized":[]}]}
{"id":"5096","document_id":"1786266","passages":[{"id":"5097","type":"title","text":["Rabbit syndrome, antidepressant use, and cerebral perfusion SPECT scan findings."],"offsets":[[0,80]]},{"id":"5098","type":"abstract","text":["The rabbit syndrome is an extrapyramidal side effect associated with chronic neuroleptic therapy. Its occurrence in a patient being treated with imipramine is described, representing the first reported case of this syndrome in conjunction with antidepressants. Repeated cerebral perfusion SPECT scans revealed decreased basal ganglia perfusion while the movement disorder was present, and a return to normal perfusion when the rabbit syndrome resolved."],"offsets":[[81,533]]}],"entities":[{"id":"5099","type":"Disease","text":["Rabbit syndrome"],"offsets":[[0,15]],"normalized":[{"db_name":"MESH","db_id":"D001480"}]},{"id":"5100","type":"Chemical","text":["antidepressant"],"offsets":[[17,31]],"normalized":[{"db_name":"MESH","db_id":"D000928"}]},{"id":"5101","type":"Disease","text":["rabbit syndrome"],"offsets":[[85,100]],"normalized":[{"db_name":"MESH","db_id":"D001480"}]},{"id":"5102","type":"Chemical","text":["imipramine"],"offsets":[[226,236]],"normalized":[{"db_name":"MESH","db_id":"D007099"}]},{"id":"5103","type":"Chemical","text":["antidepressants"],"offsets":[[325,340]],"normalized":[{"db_name":"MESH","db_id":"D000928"}]},{"id":"5104","type":"Disease","text":["decreased basal ganglia perfusion"],"offsets":[[391,424]],"normalized":[{"db_name":"MESH","db_id":"D001480"}]},{"id":"5105","type":"Disease","text":["movement disorder"],"offsets":[[435,452]],"normalized":[{"db_name":"MESH","db_id":"D009069"}]},{"id":"5106","type":"Disease","text":["rabbit syndrome"],"offsets":[[508,523]],"normalized":[{"db_name":"MESH","db_id":"D001480"}]}],"events":[],"coreferences":[],"relations":[{"id":"5107","type":"CID","arg1_id":"5102","arg2_id":"5099","normalized":[]},{"id":"5108","type":"CID","arg1_id":"5102","arg2_id":"5101","normalized":[]},{"id":"5109","type":"CID","arg1_id":"5102","arg2_id":"5104","normalized":[]},{"id":"5110","type":"CID","arg1_id":"5102","arg2_id":"5106","normalized":[]}]}
{"id":"5111","document_id":"1835291","passages":[{"id":"5112","type":"title","text":["Acute bronchodilating effects of ipratropium bromide and theophylline in chronic obstructive pulmonary disease."],"offsets":[[0,111]]},{"id":"5113","type":"abstract","text":["The bronchodilator effects of a single dose of ipratropium bromide aerosol (36 micrograms) and short-acting theophylline tablets (dose titrated to produce serum levels of 10-20 micrograms\/mL) were compared in a double-blind, placebo-controlled crossover study in 21 patients with stable, chronic obstructive pulmonary disease. Mean peak forced expiratory volume in 1 second (FEV1) increases over baseline and the proportion of patients attaining at least a 15% increase in the FEV1 (responders) were 31% and 90%, respectively, for ipratropium and 17% and 50%, respectively, for theophylline. The average FEV1 increases during the 6-hour observation period were 18% for ipratropium and 8% for theophylline. The mean duration of action was 3.8 hours with ipratropium and 2.4 hours with theophylline. While side effects were rare, those experienced after theophylline use did involve the cardiovascular and gastrointestinal systems. These results show that ipratropium is a more potent bronchodilator than oral theophylline in patients with chronic airflow obstruction."],"offsets":[[112,1178]]}],"entities":[{"id":"5114","type":"Chemical","text":["ipratropium bromide"],"offsets":[[33,52]],"normalized":[{"db_name":"MESH","db_id":"D009241"}]},{"id":"5115","type":"Chemical","text":["theophylline"],"offsets":[[57,69]],"normalized":[{"db_name":"MESH","db_id":"D013806"}]},{"id":"5116","type":"Disease","text":["chronic obstructive pulmonary disease"],"offsets":[[73,110]],"normalized":[{"db_name":"MESH","db_id":"D029424"}]},{"id":"5117","type":"Chemical","text":["ipratropium bromide"],"offsets":[[159,178]],"normalized":[{"db_name":"MESH","db_id":"D009241"}]},{"id":"5118","type":"Chemical","text":["theophylline"],"offsets":[[220,232]],"normalized":[{"db_name":"MESH","db_id":"D013806"}]},{"id":"5119","type":"Disease","text":["chronic obstructive pulmonary 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and gastrointestinal systems"],"offsets":[[997,1040]],"normalized":[{"db_name":"MESH","db_id":"D002318"},{"db_name":"MESH","db_id":"D005767"}]},{"id":"5128","type":"Disease","text":["cardiovascular","systems"],"offsets":[[997,1011],[1033,1040]],"normalized":[{"db_name":"MESH","db_id":"D002318"}]},{"id":"5129","type":"Disease","text":["gastrointestinal systems"],"offsets":[[1016,1040]],"normalized":[{"db_name":"MESH","db_id":"D005767"}]},{"id":"5130","type":"Chemical","text":["ipratropium"],"offsets":[[1066,1077]],"normalized":[{"db_name":"MESH","db_id":"D009241"}]},{"id":"5131","type":"Chemical","text":["theophylline"],"offsets":[[1120,1132]],"normalized":[{"db_name":"MESH","db_id":"D013806"}]},{"id":"5132","type":"Disease","text":["chronic airflow obstruction"],"offsets":[[1150,1177]],"normalized":[{"db_name":"MESH","db_id":"D029424"}]}],"events":[],"coreferences":[],"relations":[{"id":"5133","type":"CID","arg1_id":"5115","arg2_id":"5127","normalized":[]},{"id":"5134","type":"CID","arg1_id":"5115","arg2_id":"5128","normalized":[]},{"id":"5135","type":"CID","arg1_id":"5118","arg2_id":"5127","normalized":[]},{"id":"5136","type":"CID","arg1_id":"5118","arg2_id":"5128","normalized":[]},{"id":"5137","type":"CID","arg1_id":"5121","arg2_id":"5127","normalized":[]},{"id":"5138","type":"CID","arg1_id":"5121","arg2_id":"5128","normalized":[]},{"id":"5139","type":"CID","arg1_id":"5123","arg2_id":"5127","normalized":[]},{"id":"5140","type":"CID","arg1_id":"5123","arg2_id":"5128","normalized":[]},{"id":"5141","type":"CID","arg1_id":"5125","arg2_id":"5127","normalized":[]},{"id":"5142","type":"CID","arg1_id":"5125","arg2_id":"5128","normalized":[]},{"id":"5143","type":"CID","arg1_id":"5126","arg2_id":"5127","normalized":[]},{"id":"5144","type":"CID","arg1_id":"5126","arg2_id":"5128","normalized":[]},{"id":"5145","type":"CID","arg1_id":"5131","arg2_id":"5127","normalized":[]},{"id":"5146","type":"CID","arg1_id":"5131","arg2_id":"5128","normalized":[]},{"id":"5147","type":"CID","arg1_id":"5115","arg2_id":"5127","normalized":[]},{"id":"5148","type":"CID","arg1_id":"5115","arg2_id":"5129","normalized":[]},{"id":"5149","type":"CID","arg1_id":"5118","arg2_id":"5127","normalized":[]},{"id":"5150","type":"CID","arg1_id":"5118","arg2_id":"5129","normalized":[]},{"id":"5151","type":"CID","arg1_id":"5121","arg2_id":"5127","normalized":[]},{"id":"5152","type":"CID","arg1_id":"5121","arg2_id":"5129","normalized":[]},{"id":"5153","type":"CID","arg1_id":"5123","arg2_id":"5127","normalized":[]},{"id":"5154","type":"CID","arg1_id":"5123","arg2_id":"5129","normalized":[]},{"id":"5155","type":"CID","arg1_id":"5125","arg2_id":"5127","normalized":[]},{"id":"5156","type":"CID","arg1_id":"5125","arg2_id":"5129","normalized":[]},{"id":"5157","type":"CID","arg1_id":"5126","arg2_id":"5127","normalized":[]},{"id":"5158","type":"CID","arg1_id":"5126","arg2_id":"5129","normalized":[]},{"id":"5159","type":"CID","arg1_id":"5131","arg2_id":"5127","normalized":[]},{"id":"5160","type":"CID","arg1_id":"5131","arg2_id":"5129","normalized":[]}]}
{"id":"5161","document_id":"1919871","passages":[{"id":"5162","type":"title","text":["Irreversible damage to the medullary interstitium in experimental analgesic nephropathy in F344 rats."],"offsets":[[0,101]]},{"id":"5163","type":"abstract","text":["Renal papillary necrosis (RPN) and a decreased urinary concentrating ability developed during continuous long-term treatment with aspirin and paracetamol in female Fischer 344 rats. Renal structure and concentrating ability were examined after a recovery period of up to 18 weeks, when no analgesics were given, to investigate whether the analgesic-induced changes were reversible. There was no evidence of repair to the damaged medullary interstitial matrix, or proliferation of remaining undamaged type 1 medullary interstitial cells after the recovery period following analgesic treatment. The recovery of urinary concentrating ability was related to the length of analgesic treatment and the extent of the resulting inner medullary structural damage. During the early stages of analgesic treatment, the changes in urinary concentrating ability were reversible, but after prolonged analgesic treatment, maximum urinary concentrating ability failed to recover. This study shows that prolonged analgesic treatment in Fischer 344 rats causes progressive and irreversible damage to the interstitial matrix and type 1 interstitial cells leading to RPN. The associated urinary concentrating defect is reversible only during the early stages of structural damage to the inner medulla."],"offsets":[[102,1382]]}],"entities":[{"id":"5164","type":"Disease","text":["nephropathy"],"offsets":[[76,87]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"5165","type":"Disease","text":["Renal papillary necrosis"],"offsets":[[102,126]],"normalized":[{"db_name":"MESH","db_id":"D007681"}]},{"id":"5166","type":"Disease","text":["RPN"],"offsets":[[128,131]],"normalized":[{"db_name":"MESH","db_id":"D007681"}]},{"id":"5167","type":"Chemical","text":["aspirin"],"offsets":[[232,239]],"normalized":[{"db_name":"MESH","db_id":"D001241"}]},{"id":"5168","type":"Chemical","text":["paracetamol"],"offsets":[[244,255]],"normalized":[{"db_name":"MESH","db_id":"D000082"}]},{"id":"5169","type":"Disease","text":["RPN"],"offsets":[[1248,1251]],"normalized":[{"db_name":"MESH","db_id":"D007681"}]}],"events":[],"coreferences":[],"relations":[{"id":"5170","type":"CID","arg1_id":"5168","arg2_id":"5165","normalized":[]},{"id":"5171","type":"CID","arg1_id":"5168","arg2_id":"5166","normalized":[]},{"id":"5172","type":"CID","arg1_id":"5168","arg2_id":"5169","normalized":[]},{"id":"5173","type":"CID","arg1_id":"5167","arg2_id":"5165","normalized":[]},{"id":"5174","type":"CID","arg1_id":"5167","arg2_id":"5166","normalized":[]},{"id":"5175","type":"CID","arg1_id":"5167","arg2_id":"5169","normalized":[]}]}
{"id":"5176","document_id":"1987816","passages":[{"id":"5177","type":"title","text":["Less frequent lithium administration and lower urine volume."],"offsets":[[0,60]]},{"id":"5178","type":"abstract","text":["OBJECTIVE: This study was designed to determine whether patients maintained on a regimen of lithium on a once-per-day schedule have lower urine volumes than do patients receiving multiple doses per day. METHOD: This was a cross-sectional study of 85 patients from a lithium clinic who received different dose schedules. Patients were admitted to the hospital for measurement of lithium level, creatinine clearance, urine volume, and maximum osmolality. RESULTS: Multiple daily doses of lithium were associated with higher urine volumes. The dosing schedule, duration of lithium treatment, and daily dose of lithium did not affect maximum osmolality or creatinine clearance. CONCLUSIONS: Urine volume can be reduced by giving lithium once daily and\/or by lowering the total daily dose. Lithium-induced polyuria seems to be related to extrarenal as well as to renal effects."],"offsets":[[61,933]]}],"entities":[{"id":"5179","type":"Chemical","text":["lithium"],"offsets":[[14,21]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"5180","type":"Chemical","text":["lithium"],"offsets":[[153,160]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"5181","type":"Chemical","text":["lithium"],"offsets":[[327,334]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"5182","type":"Chemical","text":["lithium"],"offsets":[[439,446]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"5183","type":"Chemical","text":["creatinine"],"offsets":[[454,464]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"5184","type":"Chemical","text":["lithium"],"offsets":[[547,554]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"5185","type":"Chemical","text":["lithium"],"offsets":[[631,638]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"5186","type":"Chemical","text":["lithium"],"offsets":[[668,675]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"5187","type":"Chemical","text":["creatinine"],"offsets":[[713,723]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"5188","type":"Chemical","text":["lithium"],"offsets":[[786,793]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"5189","type":"Chemical","text":["Lithium"],"offsets":[[846,853]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"5190","type":"Disease","text":["polyuria"],"offsets":[[862,870]],"normalized":[{"db_name":"MESH","db_id":"D011141"}]}],"events":[],"coreferences":[],"relations":[{"id":"5191","type":"CID","arg1_id":"5179","arg2_id":"5190","normalized":[]},{"id":"5192","type":"CID","arg1_id":"5180","arg2_id":"5190","normalized":[]},{"id":"5193","type":"CID","arg1_id":"5181","arg2_id":"5190","normalized":[]},{"id":"5194","type":"CID","arg1_id":"5182","arg2_id":"5190","normalized":[]},{"id":"5195","type":"CID","arg1_id":"5184","arg2_id":"5190","normalized":[]},{"id":"5196","type":"CID","arg1_id":"5185","arg2_id":"5190","normalized":[]},{"id":"5197","type":"CID","arg1_id":"5186","arg2_id":"5190","normalized":[]},{"id":"5198","type":"CID","arg1_id":"5188","arg2_id":"5190","normalized":[]},{"id":"5199","type":"CID","arg1_id":"5189","arg2_id":"5190","normalized":[]}]}
{"id":"5200","document_id":"2054792","passages":[{"id":"5201","type":"title","text":["Effect of adriamycin combined with whole body hyperthermia on tumor and normal tissues."],"offsets":[[0,87]]},{"id":"5202","type":"abstract","text":["Thermal enhancement of Adriamycin-mediated antitumor activity and normal tissue toxicities by whole body hyperthermia were compared using a F344 rat model. Antitumor activity was studied using a tumor growth delay assay. Acute normal tissue toxicities (i.e., leukopenia and thrombocytopenia) and late normal tissue toxicities (i.e., myocardial and kidney injury) were evaluated by functional\/physiological assays and by morphological techniques. Whole body hyperthermia (120 min at 41.5 degrees C) enhanced both Adriamycin-mediated antitumor activity and toxic side effects. The thermal enhancement ratio calculated for antitumor activity was 1.6. Thermal enhancement ratios estimated for \"acute\" hematological changes were 1.3, whereas those estimated for \"late\" damage (based on morphological cardiac and renal lesions) varied between 2.4 and 4.3. Thus, while whole body hyperthermia enhances Adriamycin-mediated antitumor effect, normal tissue toxicity is also increased, and the potential therapeutic gain of the combined modality treatment is eroded."],"offsets":[[88,1143]]}],"entities":[{"id":"5203","type":"Chemical","text":["adriamycin"],"offsets":[[10,20]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"5204","type":"Disease","text":["hyperthermia"],"offsets":[[46,58]],"normalized":[{"db_name":"MESH","db_id":"D005334"}]},{"id":"5205","type":"Disease","text":["tumor"],"offsets":[[62,67]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"5206","type":"Chemical","text":["Adriamycin"],"offsets":[[111,121]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"5207","type":"Disease","text":["toxicities"],"offsets":[[168,178]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"5208","type":"Disease","text":["hyperthermia"],"offsets":[[193,205]],"normalized":[{"db_name":"MESH","db_id":"D005334"}]},{"id":"5209","type":"Disease","text":["tumor"],"offsets":[[283,288]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"5210","type":"Disease","text":["toxicities"],"offsets":[[329,339]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"5211","type":"Disease","text":["leukopenia"],"offsets":[[347,357]],"normalized":[{"db_name":"MESH","db_id":"D007970"}]},{"id":"5212","type":"Disease","text":["thrombocytopenia"],"offsets":[[362,378]],"normalized":[{"db_name":"MESH","db_id":"D013921"}]},{"id":"5213","type":"Disease","text":["toxicities"],"offsets":[[403,413]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"5214","type":"Disease","text":["myocardial and kidney injury"],"offsets":[[421,449]],"normalized":[{"db_name":"MESH","db_id":"D006331"},{"db_name":"MESH","db_id":"D007674"}]},{"id":"5215","type":"Disease","text":["myocardial","injury"],"offsets":[[421,431],[443,449]],"normalized":[{"db_name":"MESH","db_id":"D006331"}]},{"id":"5216","type":"Disease","text":["kidney injury"],"offsets":[[436,449]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"5217","type":"Disease","text":["hyperthermia"],"offsets":[[545,557]],"normalized":[{"db_name":"MESH","db_id":"D005334"}]},{"id":"5218","type":"Chemical","text":["Adriamycin"],"offsets":[[600,610]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"5219","type":"Disease","text":["cardiac and renal lesions"],"offsets":[[883,908]],"normalized":[{"db_name":"MESH","db_id":"D006331"},{"db_name":"MESH","db_id":"D007674"}]},{"id":"5220","type":"Disease","text":["cardiac","lesions"],"offsets":[[883,890],[901,908]],"normalized":[{"db_name":"MESH","db_id":"D006331"}]},{"id":"5221","type":"Disease","text":["renal lesions"],"offsets":[[895,908]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"5222","type":"Disease","text":["hyperthermia"],"offsets":[[961,973]],"normalized":[{"db_name":"MESH","db_id":"D005334"}]},{"id":"5223","type":"Chemical","text":["Adriamycin"],"offsets":[[983,993]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"5224","type":"Disease","text":["toxicity"],"offsets":[[1035,1043]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]}],"events":[],"coreferences":[],"relations":[{"id":"5225","type":"CID","arg1_id":"5203","arg2_id":"5214","normalized":[]},{"id":"5226","type":"CID","arg1_id":"5203","arg2_id":"5215","normalized":[]},{"id":"5227","type":"CID","arg1_id":"5203","arg2_id":"5219","normalized":[]},{"id":"5228","type":"CID","arg1_id":"5203","arg2_id":"5220","normalized":[]},{"id":"5229","type":"CID","arg1_id":"5206","arg2_id":"5214","normalized":[]},{"id":"5230","type":"CID","arg1_id":"5206","arg2_id":"5215","normalized":[]},{"id":"5231","type":"CID","arg1_id":"5206","arg2_id":"5219","normalized":[]},{"id":"5232","type":"CID","arg1_id":"5206","arg2_id":"5220","normalized":[]},{"id":"5233","type":"CID","arg1_id":"5218","arg2_id":"5214","normalized":[]},{"id":"5234","type":"CID","arg1_id":"5218","arg2_id":"5215","normalized":[]},{"id":"5235","type":"CID","arg1_id":"5218","arg2_id":"5219","normalized":[]},{"id":"5236","type":"CID","arg1_id":"5218","arg2_id":"5220","normalized":[]},{"id":"5237","type":"CID","arg1_id":"5223","arg2_id":"5214","normalized":[]},{"id":"5238","type":"CID","arg1_id":"5223","arg2_id":"5215","normalized":[]},{"id":"5239","type":"CID","arg1_id":"5223","arg2_id":"5219","normalized":[]},{"id":"5240","type":"CID","arg1_id":"5223","arg2_id":"5220","normalized":[]}]}
{"id":"5241","document_id":"2304736","passages":[{"id":"5242","type":"title","text":["Prazosin-induced stress incontinence."],"offsets":[[0,37]]},{"id":"5243","type":"abstract","text":["A case of genuine stress incontinence due to prazosin, a common antihypertensive drug, is presented. Prazosin exerts its antihypertensive effects through vasodilatation caused by selective blockade of postsynaptic alpha-1 adrenergic receptors. As an alpha-blocker, it also exerts a significant relaxant effect on the bladder neck and urethra. The patient's clinical course is described and correlated with initial urodynamic studies while on prazosin and subsequent studies while taking verapamil. Her incontinence resolved with the change of medication. The restoration of continence was accompanied by a substantial rise in maximum urethral pressure, maximum urethral closure pressure, and functional urethral length. Patients who present with stress incontinence while taking prazosin should change their antihypertensive medication before considering surgery, because their incontinence may resolve spontaneously with a change in drug therapy."],"offsets":[[38,985]]}],"entities":[{"id":"5244","type":"Chemical","text":["Prazosin"],"offsets":[[0,8]],"normalized":[{"db_name":"MESH","db_id":"D011224"}]},{"id":"5245","type":"Disease","text":["stress incontinence"],"offsets":[[17,36]],"normalized":[{"db_name":"MESH","db_id":"D014550"}]},{"id":"5246","type":"Disease","text":["stress incontinence"],"offsets":[[56,75]],"normalized":[{"db_name":"MESH","db_id":"D014550"}]},{"id":"5247","type":"Chemical","text":["prazosin"],"offsets":[[83,91]],"normalized":[{"db_name":"MESH","db_id":"D011224"}]},{"id":"5248","type":"Chemical","text":["Prazosin"],"offsets":[[139,147]],"normalized":[{"db_name":"MESH","db_id":"D011224"}]},{"id":"5249","type":"Chemical","text":["prazosin"],"offsets":[[480,488]],"normalized":[{"db_name":"MESH","db_id":"D011224"}]},{"id":"5250","type":"Chemical","text":["verapamil"],"offsets":[[525,534]],"normalized":[{"db_name":"MESH","db_id":"D014700"}]},{"id":"5251","type":"Disease","text":["incontinence"],"offsets":[[540,552]],"normalized":[{"db_name":"MESH","db_id":"D014549"}]},{"id":"5252","type":"Disease","text":["stress incontinence"],"offsets":[[784,803]],"normalized":[{"db_name":"MESH","db_id":"D014550"}]},{"id":"5253","type":"Chemical","text":["prazosin"],"offsets":[[817,825]],"normalized":[{"db_name":"MESH","db_id":"D011224"}]},{"id":"5254","type":"Disease","text":["incontinence"],"offsets":[[916,928]],"normalized":[{"db_name":"MESH","db_id":"D014549"}]}],"events":[],"coreferences":[],"relations":[{"id":"5255","type":"CID","arg1_id":"5244","arg2_id":"5245","normalized":[]},{"id":"5256","type":"CID","arg1_id":"5244","arg2_id":"5246","normalized":[]},{"id":"5257","type":"CID","arg1_id":"5244","arg2_id":"5252","normalized":[]},{"id":"5258","type":"CID","arg1_id":"5247","arg2_id":"5245","normalized":[]},{"id":"5259","type":"CID","arg1_id":"5247","arg2_id":"5246","normalized":[]},{"id":"5260","type":"CID","arg1_id":"5247","arg2_id":"5252","normalized":[]},{"id":"5261","type":"CID","arg1_id":"5248","arg2_id":"5245","normalized":[]},{"id":"5262","type":"CID","arg1_id":"5248","arg2_id":"5246","normalized":[]},{"id":"5263","type":"CID","arg1_id":"5248","arg2_id":"5252","normalized":[]},{"id":"5264","type":"CID","arg1_id":"5249","arg2_id":"5245","normalized":[]},{"id":"5265","type":"CID","arg1_id":"5249","arg2_id":"5246","normalized":[]},{"id":"5266","type":"CID","arg1_id":"5249","arg2_id":"5252","normalized":[]},{"id":"5267","type":"CID","arg1_id":"5253","arg2_id":"5245","normalized":[]},{"id":"5268","type":"CID","arg1_id":"5253","arg2_id":"5246","normalized":[]},{"id":"5269","type":"CID","arg1_id":"5253","arg2_id":"5252","normalized":[]}]}
{"id":"5270","document_id":"2312209","passages":[{"id":"5271","type":"title","text":["Myocardial infarction following sublingual administration of isosorbide dinitrate."],"offsets":[[0,82]]},{"id":"5272","type":"abstract","text":["A 78-year-old with healed septal necrosis suffered a recurrent myocardial infarction of the anterior wall following the administration of isosorbide dinitrate 5 mg sublingually. After detailing the course of events, we discuss the role of paradoxical coronary spasm and hypotension-mediated myocardial ischemia occurring downstream to significant coronary arterial stenosis in the pathophysiology of acute coronary insufficiency."],"offsets":[[83,512]]}],"entities":[{"id":"5273","type":"Disease","text":["Myocardial infarction"],"offsets":[[0,21]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"5274","type":"Chemical","text":["isosorbide dinitrate"],"offsets":[[61,81]],"normalized":[{"db_name":"MESH","db_id":"D007548"}]},{"id":"5275","type":"Disease","text":["necrosis"],"offsets":[[116,124]],"normalized":[{"db_name":"MESH","db_id":"D009336"}]},{"id":"5276","type":"Disease","text":["myocardial infarction"],"offsets":[[146,167]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"5277","type":"Chemical","text":["isosorbide dinitrate"],"offsets":[[221,241]],"normalized":[{"db_name":"MESH","db_id":"D007548"}]},{"id":"5278","type":"Disease","text":["spasm"],"offsets":[[343,348]],"normalized":[{"db_name":"MESH","db_id":"D013035"}]},{"id":"5279","type":"Disease","text":["hypotension"],"offsets":[[353,364]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"5280","type":"Disease","text":["myocardial ischemia"],"offsets":[[374,393]],"normalized":[{"db_name":"MESH","db_id":"D017202"}]},{"id":"5281","type":"Disease","text":["coronary arterial stenosis"],"offsets":[[430,456]],"normalized":[{"db_name":"MESH","db_id":"D023921"}]},{"id":"5282","type":"Disease","text":["acute coronary insufficiency"],"offsets":[[483,511]],"normalized":[{"db_name":"MESH","db_id":"D054058"}]}],"events":[],"coreferences":[],"relations":[{"id":"5283","type":"CID","arg1_id":"5274","arg2_id":"5273","normalized":[]},{"id":"5284","type":"CID","arg1_id":"5274","arg2_id":"5276","normalized":[]},{"id":"5285","type":"CID","arg1_id":"5277","arg2_id":"5273","normalized":[]},{"id":"5286","type":"CID","arg1_id":"5277","arg2_id":"5276","normalized":[]}]}
{"id":"5287","document_id":"2549018","passages":[{"id":"5288","type":"title","text":["Fluoxetine-induced akathisia: clinical and theoretical implications."],"offsets":[[0,68]]},{"id":"5289","type":"abstract","text":["Five patients receiving fluoxetine for the treatment of obsessive compulsive disorder or major depression developed akathisia. The typical fluoxetine-induced symptoms of restlessness, constant pacing, purposeless movements of the feet and legs, and marked anxiety were indistinguishable from those of neuroleptic-induced akathisia. Three patients who had experienced neuroleptic-induced akathisia in the past reported that the symptoms of fluoxetine-induced akathisia were identical, although somewhat milder. Akathisia appeared to be a common side effect of fluoxetine and generally responded well to treatment with the beta-adrenergic antagonist propranolol, dose reduction, or both. The authors suggest that fluoxetine-induced akathisia may be caused by serotonergically mediated inhibition of dopaminergic neurotransmission and that the pathophysiology of fluoxetine-induced akathisia and tricyclic antidepressant-induced \"jitteriness\" may be identical."],"offsets":[[69,1026]]}],"entities":[{"id":"5290","type":"Chemical","text":["Fluoxetine"],"offsets":[[0,10]],"normalized":[{"db_name":"MESH","db_id":"D005473"}]},{"id":"5291","type":"Disease","text":["akathisia"],"offsets":[[19,28]],"normalized":[{"db_name":"MESH","db_id":"D017109"}]},{"id":"5292","type":"Chemical","text":["fluoxetine"],"offsets":[[93,103]],"normalized":[{"db_name":"MESH","db_id":"D005473"}]},{"id":"5293","type":"Disease","text":["obsessive compulsive disorder"],"offsets":[[125,154]],"normalized":[{"db_name":"MESH","db_id":"D009771"}]},{"id":"5294","type":"Disease","text":["major 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{"id":"5366","document_id":"2611118","passages":[{"id":"5367","type":"title","text":["Chronic active hepatitis associated with diclofenac sodium therapy."],"offsets":[[0,67]]},{"id":"5368","type":"abstract","text":["Diclofenac sodium (Voltarol, Geigy Pharmaceuticals) is a non-steroidal anti-inflammatory derivative of phenylacetic acid. Although generally well-tolerated, asymptomatic abnormalities of liver function have been recorded and, less commonly, severe hepatitis induced by diclofenac. The patient described developed chronic active hepatitis after six months therapy with diclofenac sodium which progressed despite the withdrawal of the drug, a finding not previously reported."],"offsets":[[68,541]]}],"entities":[{"id":"5369","type":"Disease","text":["Chronic active hepatitis"],"offsets":[[0,24]],"normalized":[{"db_name":"MESH","db_id":"D006521"}]},{"id":"5370","type":"Chemical","text":["diclofenac sodium"],"offsets":[[41,58]],"normalized":[{"db_name":"MESH","db_id":"D004008"}]},{"id":"5371","type":"Chemical","text":["Diclofenac sodium"],"offsets":[[68,85]],"normalized":[{"db_name":"MESH","db_id":"D004008"}]},{"id":"5372","type":"Chemical","text":["Voltarol"],"offsets":[[87,95]],"normalized":[{"db_name":"MESH","db_id":"D004008"}]},{"id":"5373","type":"Chemical","text":["phenylacetic acid"],"offsets":[[171,188]],"normalized":[{"db_name":"MESH","db_id":"C025136"}]},{"id":"5374","type":"Disease","text":["abnormalities of liver function"],"offsets":[[238,269]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"5375","type":"Disease","text":["hepatitis"],"offsets":[[316,325]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"5376","type":"Chemical","text":["diclofenac"],"offsets":[[337,347]],"normalized":[{"db_name":"MESH","db_id":"D004008"}]},{"id":"5377","type":"Disease","text":["chronic active hepatitis"],"offsets":[[381,405]],"normalized":[{"db_name":"MESH","db_id":"D006521"}]},{"id":"5378","type":"Chemical","text":["diclofenac sodium"],"offsets":[[436,453]],"normalized":[{"db_name":"MESH","db_id":"D004008"}]}],"events":[],"coreferences":[],"relations":[{"id":"5379","type":"CID","arg1_id":"5370","arg2_id":"5374","normalized":[]},{"id":"5380","type":"CID","arg1_id":"5370","arg2_id":"5375","normalized":[]},{"id":"5381","type":"CID","arg1_id":"5371","arg2_id":"5374","normalized":[]},{"id":"5382","type":"CID","arg1_id":"5371","arg2_id":"5375","normalized":[]},{"id":"5383","type":"CID","arg1_id":"5372","arg2_id":"5374","normalized":[]},{"id":"5384","type":"CID","arg1_id":"5372","arg2_id":"5375","normalized":[]},{"id":"5385","type":"CID","arg1_id":"5376","arg2_id":"5374","normalized":[]},{"id":"5386","type":"CID","arg1_id":"5376","arg2_id":"5375","normalized":[]},{"id":"5387","type":"CID","arg1_id":"5378","arg2_id":"5374","normalized":[]},{"id":"5388","type":"CID","arg1_id":"5378","arg2_id":"5375","normalized":[]}]}
{"id":"5389","document_id":"2673163","passages":[{"id":"5390","type":"title","text":["Stroke associated with cocaine use."],"offsets":[[0,35]]},{"id":"5391","type":"abstract","text":["We describe eight patients in whom cocaine use was related to stroke and review 39 cases from the literature. Among these 47 patients the mean (+\/- SD) age was 32.5 +\/- 12.1 years; 76% (34\/45) were men. Stroke followed cocaine use by inhalation, intranasal, intravenous, and intramuscular routes. Intracranial aneurysms or arteriovenous malformations were present in 17 of 32 patients studied angiographically or at autopsy; cerebral vasculitis was present in two patients. Cerebral infarction occurred in 10 patients (22%), intracerebral hemorrhage in 22 (49%), and subarachnoid hemorrhage in 13 (29%). These data indicate that (1) the apparent incidence of stroke related to cocaine use is increasing; (2) cocaine-associated stroke occurs primarily in young adults; (3) stroke may follow any route of cocaine administration; (4) stroke after cocaine use is frequently associated with intracranial aneurysms and arteriovenous malformations; and (5) in cocaine-associated stroke, the frequency of intracranial hemorrhage exceeds that of cerebral infarction."],"offsets":[[36,1093]]}],"entities":[{"id":"5392","type":"Disease","text":["Stroke"],"offsets":[[0,6]],"normalized":[{"db_name":"MESH","db_id":"D020521"}]},{"id":"5393","type":"Chemical","text":["cocaine"],"offsets":[[23,30]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"5394","type":"Chemical","text":["cocaine"],"offsets":[[71,78]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"5395","type":"Disease","text":["stroke"],"offsets":[[98,104]],"normalized":[{"db_name":"MESH","db_id":"D020521"}]},{"id":"5396","type":"Disease","text":["Stroke"],"offsets":[[239,245]],"normalized":[{"db_name":"MESH","db_id":"D020521"}]},{"id":"5397","type":"Chemical","text":["cocaine"],"offsets":[[255,262]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"5398","type":"Disease","text":["Intracranial aneurysms"],"offsets":[[333,355]],"normalized":[{"db_name":"MESH","db_id":"D002532"}]},{"id":"5399","type":"Disease","text":["arteriovenous 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{"id":"5450","document_id":"3107448","passages":[{"id":"5451","type":"title","text":["Glyburide-induced hepatitis."],"offsets":[[0,28]]},{"id":"5452","type":"abstract","text":["Drug-induced hepatotoxicity, although common, has been reported only infrequently with sulfonylureas. For glyburide, a second-generation sulfonylurea, only two brief reports of hepatotoxicity exist. Two patients with type II diabetes mellitus developed an acute hepatitis-like syndrome soon after initiation of glyburide therapy. There was no serologic evidence of viral infection, and a liver biopsy sample showed a histologic pattern consistent with drug-induced hepatitis. Both patients recovered quickly after stopping glyburide therapy and have remained well for a follow-up period of 1 year. Glyburide can produce an acute hepatitis-like illness in some persons."],"offsets":[[29,697]]}],"entities":[{"id":"5453","type":"Chemical","text":["Glyburide"],"offsets":[[0,9]],"normalized":[{"db_name":"MESH","db_id":"D005905"}]},{"id":"5454","type":"Disease","text":["hepatitis"],"offsets":[[18,27]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"5455","type":"Disease","text":["hepatotoxicity"],"offsets":[[42,56]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"5456","type":"Chemical","text":["sulfonylureas"],"offsets":[[116,129]],"normalized":[{"db_name":"MESH","db_id":"D013453"}]},{"id":"5457","type":"Chemical","text":["glyburide"],"offsets":[[135,144]],"normalized":[{"db_name":"MESH","db_id":"D005905"}]},{"id":"5458","type":"Chemical","text":["sulfonylurea"],"offsets":[[166,178]],"normalized":[{"db_name":"MESH","db_id":"D013453"}]},{"id":"5459","type":"Disease","text":["hepatotoxicity"],"offsets":[[206,220]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"5460","type":"Disease","text":["type II diabetes mellitus"],"offsets":[[246,271]],"normalized":[{"db_name":"MESH","db_id":"D003924"}]},{"id":"5461","type":"Disease","text":["acute hepatitis-like syndrome"],"offsets":[[285,314]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"5462","type":"Chemical","text":["glyburide"],"offsets":[[340,349]],"normalized":[{"db_name":"MESH","db_id":"D005905"}]},{"id":"5463","type":"Disease","text":["viral infection"],"offsets":[[394,409]],"normalized":[{"db_name":"MESH","db_id":"D014777"}]},{"id":"5464","type":"Disease","text":["drug-induced hepatitis"],"offsets":[[481,503]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"5465","type":"Chemical","text":["glyburide"],"offsets":[[552,561]],"normalized":[{"db_name":"MESH","db_id":"D005905"}]},{"id":"5466","type":"Chemical","text":["Glyburide"],"offsets":[[627,636]],"normalized":[{"db_name":"MESH","db_id":"D005905"}]},{"id":"5467","type":"Disease","text":["acute hepatitis-like illness"],"offsets":[[652,680]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]}],"events":[],"coreferences":[],"relations":[{"id":"5468","type":"CID","arg1_id":"5453","arg2_id":"5454","normalized":[]},{"id":"5469","type":"CID","arg1_id":"5453","arg2_id":"5455","normalized":[]},{"id":"5470","type":"CID","arg1_id":"5453","arg2_id":"5459","normalized":[]},{"id":"5471","type":"CID","arg1_id":"5453","arg2_id":"5461","normalized":[]},{"id":"5472","type":"CID","arg1_id":"5453","arg2_id":"5464","normalized":[]},{"id":"5473","type":"CID","arg1_id":"5453","arg2_id":"5467","normalized":[]},{"id":"5474","type":"CID","arg1_id":"5457","arg2_id":"5454","normalized":[]},{"id":"5475","type":"CID","arg1_id":"5457","arg2_id":"5455","normalized":[]},{"id":"5476","type":"CID","arg1_id":"5457","arg2_id":"5459","normalized":[]},{"id":"5477","type":"CID","arg1_id":"5457","arg2_id":"5461","normalized":[]},{"id":"5478","type":"CID","arg1_id":"5457","arg2_id":"5464","normalized":[]},{"id":"5479","type":"CID","arg1_id":"5457","arg2_id":"5467","normalized":[]},{"id":"5480","type":"CID","arg1_id":"5462","arg2_id":"5454","normalized":[]},{"id":"5481","type":"CID","arg1_id":"5462","arg2_id":"5455","normalized":[]},{"id":"5482","type":"CID","arg1_id":"5462","arg2_id":"5459","normalized":[]},{"id":"5483","type":"CID","arg1_id":"5462","arg2_id":"5461","normalized":[]},{"id":"5484","type":"CID","arg1_id":"5462","arg2_id":"5464","normalized":[]},{"id":"5485","type":"CID","arg1_id":"5462","arg2_id":"5467","normalized":[]},{"id":"5486","type":"CID","arg1_id":"5465","arg2_id":"5454","normalized":[]},{"id":"5487","type":"CID","arg1_id":"5465","arg2_id":"5455","normalized":[]},{"id":"5488","type":"CID","arg1_id":"5465","arg2_id":"5459","normalized":[]},{"id":"5489","type":"CID","arg1_id":"5465","arg2_id":"5461","normalized":[]},{"id":"5490","type":"CID","arg1_id":"5465","arg2_id":"5464","normalized":[]},{"id":"5491","type":"CID","arg1_id":"5465","arg2_id":"5467","normalized":[]},{"id":"5492","type":"CID","arg1_id":"5466","arg2_id":"5454","normalized":[]},{"id":"5493","type":"CID","arg1_id":"5466","arg2_id":"5455","normalized":[]},{"id":"5494","type":"CID","arg1_id":"5466","arg2_id":"5459","normalized":[]},{"id":"5495","type":"CID","arg1_id":"5466","arg2_id":"5461","normalized":[]},{"id":"5496","type":"CID","arg1_id":"5466","arg2_id":"5464","normalized":[]},{"id":"5497","type":"CID","arg1_id":"5466","arg2_id":"5467","normalized":[]}]}
{"id":"5498","document_id":"3341566","passages":[{"id":"5499","type":"title","text":["Systolic pressure variation is greater during hemorrhage than during sodium nitroprusside-induced hypotension in ventilated dogs."],"offsets":[[0,129]]},{"id":"5500","type":"abstract","text":["The systolic pressure variation (SPV), which is the difference between the maximal and minimal values of the systolic blood pressure (SBP) after one positive-pressure breath, was studied in ventilated dogs subjected to hypotension. Mean arterial pressure was decreased to 50 mm Hg for 30 minutes either by hemorrhage (HEM, n = 7) or by continuous infusion of sodium nitroprusside (SNP, n = 7). During HEM-induced hypotension the cardiac output was significantly lower and systemic vascular resistance higher compared with that in the SNP group. The systemic, central venous, pulmonary capillary wedge pressures, and heart rates, were similar in the two groups. Analysis of the respiratory changes in the arterial pressure waveform enabled differentiation between the two groups. The SPV during hypotension was 15.7 +\/- 6.7 mm Hg in the HEM group, compared with 9.1 +\/- 2.0 mm Hg in the SNP group (P less than 0.02). The delta down, which is the measure of decrease of SBP after a mechanical breath, was 20.3 +\/- 8.4 and 10.1 +\/- 3.8 mm Hg in the HEM and SNP groups, respectively, during hypotension (P less than 0.02). It is concluded that increases in the SPV and the delta down are characteristic of a hypotensive state due to a predominant decrease in preload. They are thus more important during absolute hypovolemia than during deliberate hypotension."],"offsets":[[130,1486]]}],"entities":[{"id":"5501","type":"Disease","text":["hemorrhage"],"offsets":[[46,56]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"5502","type":"Chemical","text":["sodium nitroprusside"],"offsets":[[69,89]],"normalized":[{"db_name":"MESH","db_id":"D009599"}]},{"id":"5503","type":"Disease","text":["hypotension"],"offsets":[[98,109]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"5504","type":"Disease","text":["hypotension"],"offsets":[[349,360]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"5505","type":"Disease","text":["hemorrhage"],"offsets":[[436,446]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"5506","type":"Disease","text":["HEM"],"offsets":[[448,451]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"5507","type":"Chemical","text":["sodium nitroprusside"],"offsets":[[489,509]],"normalized":[{"db_name":"MESH","db_id":"D009599"}]},{"id":"5508","type":"Chemical","text":["SNP"],"offsets":[[511,514]],"normalized":[{"db_name":"MESH","db_id":"D009599"}]},{"id":"5509","type":"Disease","text":["HEM"],"offsets":[[531,534]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"5510","type":"Disease","text":["hypotension"],"offsets":[[543,554]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"5511","type":"Chemical","text":["SNP"],"offsets":[[664,667]],"normalized":[{"db_name":"MESH","db_id":"D009599"}]},{"id":"5512","type":"Disease","text":["hypotension"],"offsets":[[924,935]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"5513","type":"Disease","text":["HEM"],"offsets":[[966,969]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"5514","type":"Chemical","text":["SNP"],"offsets":[[1016,1019]],"normalized":[{"db_name":"MESH","db_id":"D009599"}]},{"id":"5515","type":"Disease","text":["HEM"],"offsets":[[1176,1179]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"5516","type":"Chemical","text":["SNP"],"offsets":[[1184,1187]],"normalized":[{"db_name":"MESH","db_id":"D009599"}]},{"id":"5517","type":"Disease","text":["hypotension"],"offsets":[[1217,1228]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"5518","type":"Disease","text":["hypotensive"],"offsets":[[1334,1345]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"5519","type":"Disease","text":["hypovolemia"],"offsets":[[1439,1450]],"normalized":[{"db_name":"MESH","db_id":"D020896"}]},{"id":"5520","type":"Disease","text":["hypotension"],"offsets":[[1474,1485]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]}],"events":[],"coreferences":[],"relations":[{"id":"5521","type":"CID","arg1_id":"5502","arg2_id":"5503","normalized":[]},{"id":"5522","type":"CID","arg1_id":"5502","arg2_id":"5504","normalized":[]},{"id":"5523","type":"CID","arg1_id":"5502","arg2_id":"5510","normalized":[]},{"id":"5524","type":"CID","arg1_id":"5502","arg2_id":"5512","normalized":[]},{"id":"5525","type":"CID","arg1_id":"5502","arg2_id":"5517","normalized":[]},{"id":"5526","type":"CID","arg1_id":"5502","arg2_id":"5518","normalized":[]},{"id":"5527","type":"CID","arg1_id":"5502","arg2_id":"5520","normalized":[]},{"id":"5528","type":"CID","arg1_id":"5507","arg2_id":"5503","normalized":[]},{"id":"5529","type":"CID","arg1_id":"5507","arg2_id":"5504","normalized":[]},{"id":"5530","type":"CID","arg1_id":"5507","arg2_id":"5510","normalized":[]},{"id":"5531","type":"CID","arg1_id":"5507","arg2_id":"5512","normalized":[]},{"id":"5532","type":"CID","arg1_id":"5507","arg2_id":"5517","normalized":[]},{"id":"5533","type":"CID","arg1_id":"5507","arg2_id":"5518","normalized":[]},{"id":"5534","type":"CID","arg1_id":"5507","arg2_id":"5520","normalized":[]},{"id":"5535","type":"CID","arg1_id":"5508","arg2_id":"5503","normalized":[]},{"id":"5536","type":"CID","arg1_id":"5508","arg2_id":"5504","normalized":[]},{"id":"5537","type":"CID","arg1_id":"5508","arg2_id":"5510","normalized":[]},{"id":"5538","type":"CID","arg1_id":"5508","arg2_id":"5512","normalized":[]},{"id":"5539","type":"CID","arg1_id":"5508","arg2_id":"5517","normalized":[]},{"id":"5540","type":"CID","arg1_id":"5508","arg2_id":"5518","normalized":[]},{"id":"5541","type":"CID","arg1_id":"5508","arg2_id":"5520","normalized":[]},{"id":"5542","type":"CID","arg1_id":"5511","arg2_id":"5503","normalized":[]},{"id":"5543","type":"CID","arg1_id":"5511","arg2_id":"5504","normalized":[]},{"id":"5544","type":"CID","arg1_id":"5511","arg2_id":"5510","normalized":[]},{"id":"5545","type":"CID","arg1_id":"5511","arg2_id":"5512","normalized":[]},{"id":"5546","type":"CID","arg1_id":"5511","arg2_id":"5517","normalized":[]},{"id":"5547","type":"CID","arg1_id":"5511","arg2_id":"5518","normalized":[]},{"id":"5548","type":"CID","arg1_id":"5511","arg2_id":"5520","normalized":[]},{"id":"5549","type":"CID","arg1_id":"5514","arg2_id":"5503","normalized":[]},{"id":"5550","type":"CID","arg1_id":"5514","arg2_id":"5504","normalized":[]},{"id":"5551","type":"CID","arg1_id":"5514","arg2_id":"5510","normalized":[]},{"id":"5552","type":"CID","arg1_id":"5514","arg2_id":"5512","normalized":[]},{"id":"5553","type":"CID","arg1_id":"5514","arg2_id":"5517","normalized":[]},{"id":"5554","type":"CID","arg1_id":"5514","arg2_id":"5518","normalized":[]},{"id":"5555","type":"CID","arg1_id":"5514","arg2_id":"5520","normalized":[]},{"id":"5556","type":"CID","arg1_id":"5516","arg2_id":"5503","normalized":[]},{"id":"5557","type":"CID","arg1_id":"5516","arg2_id":"5504","normalized":[]},{"id":"5558","type":"CID","arg1_id":"5516","arg2_id":"5510","normalized":[]},{"id":"5559","type":"CID","arg1_id":"5516","arg2_id":"5512","normalized":[]},{"id":"5560","type":"CID","arg1_id":"5516","arg2_id":"5517","normalized":[]},{"id":"5561","type":"CID","arg1_id":"5516","arg2_id":"5518","normalized":[]},{"id":"5562","type":"CID","arg1_id":"5516","arg2_id":"5520","normalized":[]}]}
{"id":"5563","document_id":"3564823","passages":[{"id":"5564","type":"title","text":["Drug-induced arterial spasm relieved by lidocaine. Case report."],"offsets":[[0,63]]},{"id":"5565","type":"abstract","text":["Following major intracranial surgery in a 35-year-old man, sodium pentothal was intravenously infused to minimize cerebral ischaemia. Intense vasospasm with threatened gangrene arose in the arm used for the infusion. Since the cranial condition precluded use of more usual methods, lidocaine was given intra-arterially, with careful cardiovascular monitoring, to counteract the vasospasm. The treatment was rapidly successful."],"offsets":[[64,490]]}],"entities":[{"id":"5566","type":"Disease","text":["spasm"],"offsets":[[22,27]],"normalized":[{"db_name":"MESH","db_id":"D013035"}]},{"id":"5567","type":"Chemical","text":["lidocaine"],"offsets":[[40,49]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"5568","type":"Chemical","text":["sodium pentothal"],"offsets":[[123,139]],"normalized":[{"db_name":"MESH","db_id":"D013874"}]},{"id":"5569","type":"Disease","text":["cerebral ischaemia"],"offsets":[[178,196]],"normalized":[{"db_name":"MESH","db_id":"D002545"}]},{"id":"5570","type":"Disease","text":["vasospasm"],"offsets":[[206,215]],"normalized":[{"db_name":"MESH","db_id":"D020301"}]},{"id":"5571","type":"Disease","text":["gangrene"],"offsets":[[232,240]],"normalized":[{"db_name":"MESH","db_id":"D005734"}]},{"id":"5572","type":"Chemical","text":["lidocaine"],"offsets":[[346,355]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"5573","type":"Disease","text":["vasospasm"],"offsets":[[442,451]],"normalized":[{"db_name":"MESH","db_id":"D020301"}]}],"events":[],"coreferences":[],"relations":[{"id":"5574","type":"CID","arg1_id":"5568","arg2_id":"5566","normalized":[]}]}
{"id":"5575","document_id":"3676049","passages":[{"id":"5576","type":"title","text":["Cerebral blood flow and metabolism during isoflurane-induced hypotension in patients subjected to surgery for cerebral aneurysms."],"offsets":[[0,129]]},{"id":"5577","type":"abstract","text":["Cerebral blood flow and cerebral metabolic rate for oxygen were measured during isoflurane-induced hypotension in 10 patients subjected to craniotomy for clipping of a cerebral aneurysm. Flow and metabolism were measured 5-13 days after the subarachnoid haemorrhage by a modification of the classical Kety-Schmidt technique using xenon-133 i.v. Anaesthesia was maintained with an inspired isoflurane concentration of 0.75% (plus 67% nitrous oxide in oxygen), during which CBF and CMRO2 were 34.3 +\/- 2.1 ml\/100 g min-1 and 2.32 +\/- 0.16 ml\/100 g min-1 at PaCO2 4.1 +\/- 0.1 kPa (mean +\/- SEM). Controlled hypotension to an average MAP of 50-55 mm Hg was induced by increasing the dose of isoflurane, and maintained at an inspired concentration of 2.2 +\/- 0.2%. This resulted in a significant decrease in CMRO2 (to 1.73 +\/- 0.16 ml\/100 g min-1), while CBF was unchanged. After the clipping of the aneurysm the isoflurane concentration was reduced to 0.75%. There was a significant increase in CBF, although CMRO2 was unchanged, compared with pre-hypotensive values. These changes might offer protection to brain tissue during periods of induced hypotension."],"offsets":[[130,1285]]}],"entities":[{"id":"5578","type":"Chemical","text":["isoflurane"],"offsets":[[42,52]],"normalized":[{"db_name":"MESH","db_id":"D007530"}]},{"id":"5579","type":"Disease","text":["hypotension"],"offsets":[[61,72]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"5580","type":"Disease","text":["cerebral aneurysms"],"offsets":[[110,128]],"normalized":[{"db_name":"MESH","db_id":"D002532"}]},{"id":"5581","type":"Chemical","text":["oxygen"],"offsets":[[182,188]],"normalized":[{"db_name":"MESH","db_id":"D010100"}]},{"id":"5582","type":"Chemical","text":["isoflurane"],"offsets":[[210,220]],"normalized":[{"db_name":"MESH","db_id":"D007530"}]},{"id":"5583","type":"Disease","text":["hypotension"],"offsets":[[229,240]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"5584","type":"Disease","text":["cerebral aneurysm"],"offsets":[[298,315]],"normalized":[{"db_name":"MESH","db_id":"D002532"}]},{"id":"5585","type":"Disease","text":["subarachnoid haemorrhage"],"offsets":[[371,395]],"normalized":[{"db_name":"MESH","db_id":"D013345"}]},{"id":"5586","type":"Chemical","text":["xenon"],"offsets":[[460,465]],"normalized":[{"db_name":"MESH","db_id":"D014978"}]},{"id":"5587","type":"Chemical","text":["isoflurane"],"offsets":[[519,529]],"normalized":[{"db_name":"MESH","db_id":"D007530"}]},{"id":"5588","type":"Chemical","text":["nitrous oxide"],"offsets":[[563,576]],"normalized":[{"db_name":"MESH","db_id":"D009609"}]},{"id":"5589","type":"Chemical","text":["oxygen"],"offsets":[[580,586]],"normalized":[{"db_name":"MESH","db_id":"D010100"}]},{"id":"5590","type":"Disease","text":["hypotension"],"offsets":[[734,745]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"5591","type":"Chemical","text":["Hg"],"offsets":[[776,778]],"normalized":[{"db_name":"MESH","db_id":"D008628"}]},{"id":"5592","type":"Chemical","text":["isoflurane"],"offsets":[[817,827]],"normalized":[{"db_name":"MESH","db_id":"D007530"}]},{"id":"5593","type":"Disease","text":["aneurysm"],"offsets":[[1025,1033]],"normalized":[{"db_name":"MESH","db_id":"D000783"}]},{"id":"5594","type":"Chemical","text":["isoflurane"],"offsets":[[1038,1048]],"normalized":[{"db_name":"MESH","db_id":"D007530"}]},{"id":"5595","type":"Disease","text":["hypotensive"],"offsets":[[1174,1185]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"5596","type":"Disease","text":["hypotension"],"offsets":[[1273,1284]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]}],"events":[],"coreferences":[],"relations":[{"id":"5597","type":"CID","arg1_id":"5578","arg2_id":"5579","normalized":[]},{"id":"5598","type":"CID","arg1_id":"5578","arg2_id":"5583","normalized":[]},{"id":"5599","type":"CID","arg1_id":"5578","arg2_id":"5590","normalized":[]},{"id":"5600","type":"CID","arg1_id":"5578","arg2_id":"5595","normalized":[]},{"id":"5601","type":"CID","arg1_id":"5578","arg2_id":"5596","normalized":[]},{"id":"5602","type":"CID","arg1_id":"5582","arg2_id":"5579","normalized":[]},{"id":"5603","type":"CID","arg1_id":"5582","arg2_id":"5583","normalized":[]},{"id":"5604","type":"CID","arg1_id":"5582","arg2_id":"5590","normalized":[]},{"id":"5605","type":"CID","arg1_id":"5582","arg2_id":"5595","normalized":[]},{"id":"5606","type":"CID","arg1_id":"5582","arg2_id":"5596","normalized":[]},{"id":"5607","type":"CID","arg1_id":"5587","arg2_id":"5579","normalized":[]},{"id":"5608","type":"CID","arg1_id":"5587","arg2_id":"5583","normalized":[]},{"id":"5609","type":"CID","arg1_id":"5587","arg2_id":"5590","normalized":[]},{"id":"5610","type":"CID","arg1_id":"5587","arg2_id":"5595","normalized":[]},{"id":"5611","type":"CID","arg1_id":"5587","arg2_id":"5596","normalized":[]},{"id":"5612","type":"CID","arg1_id":"5592","arg2_id":"5579","normalized":[]},{"id":"5613","type":"CID","arg1_id":"5592","arg2_id":"5583","normalized":[]},{"id":"5614","type":"CID","arg1_id":"5592","arg2_id":"5590","normalized":[]},{"id":"5615","type":"CID","arg1_id":"5592","arg2_id":"5595","normalized":[]},{"id":"5616","type":"CID","arg1_id":"5592","arg2_id":"5596","normalized":[]},{"id":"5617","type":"CID","arg1_id":"5594","arg2_id":"5579","normalized":[]},{"id":"5618","type":"CID","arg1_id":"5594","arg2_id":"5583","normalized":[]},{"id":"5619","type":"CID","arg1_id":"5594","arg2_id":"5590","normalized":[]},{"id":"5620","type":"CID","arg1_id":"5594","arg2_id":"5595","normalized":[]},{"id":"5621","type":"CID","arg1_id":"5594","arg2_id":"5596","normalized":[]}]}
{"id":"5622","document_id":"3719553","passages":[{"id":"5623","type":"title","text":["Allergic reaction to 5-fluorouracil infusion."],"offsets":[[0,45]]},{"id":"5624","type":"abstract","text":["An allergic reaction consisting of angioneurotic edema secondary to continuous infusion 5-fluorouracil occurred in a patient with recurrent carcinoma of the oral cavity, cirrhosis, and cisplatin-induced impaired renal function. This reaction occurred during the sixth and seventh courses of infusional chemotherapy. Oral diphenhydramine and prednisone were ineffective in preventing the recurrence of the allergic reaction. Discontinuance of effective chemotherapy in this patient during partial remission resulted in fatal disease progression."],"offsets":[[46,590]]}],"entities":[{"id":"5625","type":"Disease","text":["Allergic reaction"],"offsets":[[0,17]],"normalized":[{"db_name":"MESH","db_id":"D004342"}]},{"id":"5626","type":"Chemical","text":["5-fluorouracil"],"offsets":[[21,35]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"5627","type":"Disease","text":["allergic reaction"],"offsets":[[49,66]],"normalized":[{"db_name":"MESH","db_id":"D004342"}]},{"id":"5628","type":"Disease","text":["angioneurotic edema"],"offsets":[[81,100]],"normalized":[{"db_name":"MESH","db_id":"D000799"}]},{"id":"5629","type":"Chemical","text":["5-fluorouracil"],"offsets":[[134,148]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"5630","type":"Disease","text":["carcinoma of the oral cavity"],"offsets":[[186,214]],"normalized":[{"db_name":"MESH","db_id":"D009062"}]},{"id":"5631","type":"Disease","text":["cirrhosis"],"offsets":[[216,225]],"normalized":[{"db_name":"MESH","db_id":"D005355"}]},{"id":"5632","type":"Chemical","text":["cisplatin"],"offsets":[[231,240]],"normalized":[{"db_name":"MESH","db_id":"D002945"}]},{"id":"5633","type":"Disease","text":["impaired renal function"],"offsets":[[249,272]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"5634","type":"Chemical","text":["diphenhydramine"],"offsets":[[367,382]],"normalized":[{"db_name":"MESH","db_id":"D004155"}]},{"id":"5635","type":"Chemical","text":["prednisone"],"offsets":[[387,397]],"normalized":[{"db_name":"MESH","db_id":"D011241"}]},{"id":"5636","type":"Disease","text":["allergic reaction"],"offsets":[[451,468]],"normalized":[{"db_name":"MESH","db_id":"D004342"}]}],"events":[],"coreferences":[],"relations":[{"id":"5637","type":"CID","arg1_id":"5626","arg2_id":"5628","normalized":[]},{"id":"5638","type":"CID","arg1_id":"5629","arg2_id":"5628","normalized":[]}]}
{"id":"5639","document_id":"4008111","passages":[{"id":"5640","type":"title","text":["Amiodarone-induced sinoatrial block."],"offsets":[[0,36]]},{"id":"5641","type":"abstract","text":["We observed sinoatrial block due to chronic amiodarone administration in a 5-year-old boy with primary cardiomyopathy, Wolff-Parkinson-White syndrome and supraventricular tachycardia. Reduction in the dosage of amiodarone resulted in the disappearance of the sinoatrial block and the persistence of asymptomatic sinus bradycardia."],"offsets":[[37,367]]}],"entities":[{"id":"5642","type":"Chemical","text":["Amiodarone"],"offsets":[[0,10]],"normalized":[{"db_name":"MESH","db_id":"D000638"}]},{"id":"5643","type":"Disease","text":["sinoatrial block"],"offsets":[[19,35]],"normalized":[{"db_name":"MESH","db_id":"D012848"}]},{"id":"5644","type":"Disease","text":["sinoatrial block"],"offsets":[[49,65]],"normalized":[{"db_name":"MESH","db_id":"D012848"}]},{"id":"5645","type":"Chemical","text":["amiodarone"],"offsets":[[81,91]],"normalized":[{"db_name":"MESH","db_id":"D000638"}]},{"id":"5646","type":"Disease","text":["primary cardiomyopathy"],"offsets":[[132,154]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"5647","type":"Disease","text":["Wolff-Parkinson-White syndrome"],"offsets":[[156,186]],"normalized":[{"db_name":"MESH","db_id":"D014927"}]},{"id":"5648","type":"Disease","text":["supraventricular tachycardia"],"offsets":[[191,219]],"normalized":[{"db_name":"MESH","db_id":"D013617"}]},{"id":"5649","type":"Chemical","text":["amiodarone"],"offsets":[[248,258]],"normalized":[{"db_name":"MESH","db_id":"D000638"}]},{"id":"5650","type":"Disease","text":["sinoatrial block"],"offsets":[[296,312]],"normalized":[{"db_name":"MESH","db_id":"D012848"}]},{"id":"5651","type":"Disease","text":["sinus bradycardia"],"offsets":[[349,366]],"normalized":[{"db_name":"MESH","db_id":"D012804"}]}],"events":[],"coreferences":[],"relations":[{"id":"5652","type":"CID","arg1_id":"5642","arg2_id":"5643","normalized":[]},{"id":"5653","type":"CID","arg1_id":"5642","arg2_id":"5644","normalized":[]},{"id":"5654","type":"CID","arg1_id":"5642","arg2_id":"5650","normalized":[]},{"id":"5655","type":"CID","arg1_id":"5645","arg2_id":"5643","normalized":[]},{"id":"5656","type":"CID","arg1_id":"5645","arg2_id":"5644","normalized":[]},{"id":"5657","type":"CID","arg1_id":"5645","arg2_id":"5650","normalized":[]},{"id":"5658","type":"CID","arg1_id":"5649","arg2_id":"5643","normalized":[]},{"id":"5659","type":"CID","arg1_id":"5649","arg2_id":"5644","normalized":[]},{"id":"5660","type":"CID","arg1_id":"5649","arg2_id":"5650","normalized":[]}]}
{"id":"5661","document_id":"6133211","passages":[{"id":"5662","type":"title","text":["Possible teratogenicity of sulphasalazine."],"offsets":[[0,42]]},{"id":"5663","type":"abstract","text":["Three infants, born of two mothers with inflammatory bowel disease who received treatment with sulphasalazine throughout pregnancy, were found to have major congenital anomalies. In the singleton pregnancy, the mother had ulcerative colitis, and the infant, a male, had coarctation of the aorta and a ventricular septal defect. In the twin pregnancy, the mother had Crohn's disease. The first twin, a female, had a left Potter-type IIa polycystic kidney and a rudimentary left uterine cornu. The second twin, a male, had some features of Potter's facies, hypoplastic lungs, absent kidneys and ureters, and talipes equinovarus. Despite reports to the contrary, it is suggested that sulphasalazine may be teratogenic."],"offsets":[[43,758]]}],"entities":[{"id":"5664","type":"Chemical","text":["sulphasalazine"],"offsets":[[27,41]],"normalized":[{"db_name":"MESH","db_id":"D012460"}]},{"id":"5665","type":"Disease","text":["inflammatory bowel disease"],"offsets":[[83,109]],"normalized":[{"db_name":"MESH","db_id":"D015212"}]},{"id":"5666","type":"Chemical","text":["sulphasalazine"],"offsets":[[138,152]],"normalized":[{"db_name":"MESH","db_id":"D012460"}]},{"id":"5667","type":"Disease","text":["congenital anomalies"],"offsets":[[200,220]],"normalized":[{"db_name":"MESH","db_id":"D000013"}]},{"id":"5668","type":"Disease","text":["ulcerative colitis"],"offsets":[[265,283]],"normalized":[{"db_name":"MESH","db_id":"D003093"}]},{"id":"5669","type":"Disease","text":["coarctation of the aorta"],"offsets":[[313,337]],"normalized":[{"db_name":"MESH","db_id":"D001017"}]},{"id":"5670","type":"Disease","text":["ventricular septal defect"],"offsets":[[344,369]],"normalized":[{"db_name":"MESH","db_id":"D006345"}]},{"id":"5671","type":"Disease","text":["Crohn's disease"],"offsets":[[409,424]],"normalized":[{"db_name":"MESH","db_id":"D003424"}]},{"id":"5672","type":"Disease","text":["Potter-type IIa polycystic kidney"],"offsets":[[463,496]],"normalized":[{"db_name":"MESH","db_id":"D007690"}]},{"id":"5673","type":"Disease","text":["rudimentary left uterine cornu"],"offsets":[[503,533]],"normalized":[]},{"id":"5674","type":"Disease","text":["Potter's facies"],"offsets":[[581,596]],"normalized":[]},{"id":"5675","type":"Disease","text":["hypoplastic lungs"],"offsets":[[598,615]],"normalized":[]},{"id":"5676","type":"Disease","text":["absent kidneys and ureters"],"offsets":[[617,643]],"normalized":[]},{"id":"5677","type":"Disease","text":["talipes equinovarus"],"offsets":[[649,668]],"normalized":[{"db_name":"MESH","db_id":"D003025"}]},{"id":"5678","type":"Chemical","text":["sulphasalazine"],"offsets":[[724,738]],"normalized":[{"db_name":"MESH","db_id":"D012460"}]}],"events":[],"coreferences":[],"relations":[{"id":"5679","type":"CID","arg1_id":"5664","arg2_id":"5677","normalized":[]},{"id":"5680","type":"CID","arg1_id":"5666","arg2_id":"5677","normalized":[]},{"id":"5681","type":"CID","arg1_id":"5678","arg2_id":"5677","normalized":[]},{"id":"5682","type":"CID","arg1_id":"5664","arg2_id":"5669","normalized":[]},{"id":"5683","type":"CID","arg1_id":"5666","arg2_id":"5669","normalized":[]},{"id":"5684","type":"CID","arg1_id":"5678","arg2_id":"5669","normalized":[]},{"id":"5685","type":"CID","arg1_id":"5664","arg2_id":"5670","normalized":[]},{"id":"5686","type":"CID","arg1_id":"5666","arg2_id":"5670","normalized":[]},{"id":"5687","type":"CID","arg1_id":"5678","arg2_id":"5670","normalized":[]},{"id":"5688","type":"CID","arg1_id":"5664","arg2_id":"5672","normalized":[]},{"id":"5689","type":"CID","arg1_id":"5666","arg2_id":"5672","normalized":[]},{"id":"5690","type":"CID","arg1_id":"5678","arg2_id":"5672","normalized":[]}]}
{"id":"5691","document_id":"6503301","passages":[{"id":"5692","type":"title","text":["Veno-occlusive liver disease after dacarbazine therapy (DTIC) for melanoma."],"offsets":[[0,75]]},{"id":"5693","type":"abstract","text":["A case of veno-occlusive disease of the liver with fatal outcome after dacarbazine (DTIC) therapy for melanoma is reported. There was a fulminant clinical course from start of symptoms until death. At autopsy the liver was enlarged and firm with signs of venous congestion. Small- and medium-sized hepatic veins were blocked by thrombosis. Eosinophilic infiltrations were found around the vessels. Published cases from the literature are reviewed and pertinent features discussed."],"offsets":[[76,556]]}],"entities":[{"id":"5694","type":"Disease","text":["Veno-occlusive liver disease"],"offsets":[[0,28]],"normalized":[{"db_name":"MESH","db_id":"D006504"}]},{"id":"5695","type":"Chemical","text":["dacarbazine"],"offsets":[[35,46]],"normalized":[{"db_name":"MESH","db_id":"D003606"}]},{"id":"5696","type":"Chemical","text":["DTIC"],"offsets":[[56,60]],"normalized":[{"db_name":"MESH","db_id":"D003606"}]},{"id":"5697","type":"Disease","text":["melanoma"],"offsets":[[66,74]],"normalized":[{"db_name":"MESH","db_id":"D008545"}]},{"id":"5698","type":"Disease","text":["veno-occlusive disease of the liver"],"offsets":[[86,121]],"normalized":[{"db_name":"MESH","db_id":"D006504"}]},{"id":"5699","type":"Chemical","text":["dacarbazine"],"offsets":[[147,158]],"normalized":[{"db_name":"MESH","db_id":"D003606"}]},{"id":"5700","type":"Chemical","text":["DTIC"],"offsets":[[160,164]],"normalized":[{"db_name":"MESH","db_id":"D003606"}]},{"id":"5701","type":"Disease","text":["melanoma"],"offsets":[[178,186]],"normalized":[{"db_name":"MESH","db_id":"D008545"}]},{"id":"5702","type":"Disease","text":["death"],"offsets":[[267,272]],"normalized":[{"db_name":"MESH","db_id":"D003643"}]},{"id":"5703","type":"Disease","text":["venous congestion"],"offsets":[[331,348]],"normalized":[{"db_name":"MESH","db_id":"D006940"}]},{"id":"5704","type":"Disease","text":["thrombosis"],"offsets":[[404,414]],"normalized":[{"db_name":"MESH","db_id":"D013927"}]}],"events":[],"coreferences":[],"relations":[{"id":"5705","type":"CID","arg1_id":"5695","arg2_id":"5694","normalized":[]},{"id":"5706","type":"CID","arg1_id":"5695","arg2_id":"5698","normalized":[]},{"id":"5707","type":"CID","arg1_id":"5696","arg2_id":"5694","normalized":[]},{"id":"5708","type":"CID","arg1_id":"5696","arg2_id":"5698","normalized":[]},{"id":"5709","type":"CID","arg1_id":"5699","arg2_id":"5694","normalized":[]},{"id":"5710","type":"CID","arg1_id":"5699","arg2_id":"5698","normalized":[]},{"id":"5711","type":"CID","arg1_id":"5700","arg2_id":"5694","normalized":[]},{"id":"5712","type":"CID","arg1_id":"5700","arg2_id":"5698","normalized":[]}]}
{"id":"5713","document_id":"6727060","passages":[{"id":"5714","type":"title","text":["A case of tardive dyskinesia caused by metoclopramide."],"offsets":[[0,54]]},{"id":"5715","type":"abstract","text":["Abnormal involuntary movements appeared in the mouth, tongue, neck and abdomen of a 64-year-old male patient after he took metoclopramide for gastrointestinal disorder in a regimen of 30 mg per day for a total of about 260 days. The symptoms exacerbated to a maximum in a month. When the metoclopramide administration was discontinued, the abnormal movements gradually improved to a considerable extent. Attention to the possible induction of specific tardive dyskinesia is called for in the use of this drug."],"offsets":[[55,564]]}],"entities":[{"id":"5716","type":"Disease","text":["tardive dyskinesia"],"offsets":[[10,28]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"5717","type":"Chemical","text":["metoclopramide"],"offsets":[[39,53]],"normalized":[{"db_name":"MESH","db_id":"D008787"}]},{"id":"5718","type":"Disease","text":["Abnormal involuntary movements"],"offsets":[[55,85]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"5719","type":"Chemical","text":["metoclopramide"],"offsets":[[178,192]],"normalized":[{"db_name":"MESH","db_id":"D008787"}]},{"id":"5720","type":"Disease","text":["gastrointestinal disorder"],"offsets":[[197,222]],"normalized":[{"db_name":"MESH","db_id":"D005767"}]},{"id":"5721","type":"Chemical","text":["metoclopramide"],"offsets":[[343,357]],"normalized":[{"db_name":"MESH","db_id":"D008787"}]},{"id":"5722","type":"Disease","text":["abnormal movements"],"offsets":[[395,413]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"5723","type":"Disease","text":["tardive dyskinesia"],"offsets":[[507,525]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]}],"events":[],"coreferences":[],"relations":[{"id":"5724","type":"CID","arg1_id":"5717","arg2_id":"5716","normalized":[]},{"id":"5725","type":"CID","arg1_id":"5717","arg2_id":"5718","normalized":[]},{"id":"5726","type":"CID","arg1_id":"5717","arg2_id":"5722","normalized":[]},{"id":"5727","type":"CID","arg1_id":"5717","arg2_id":"5723","normalized":[]},{"id":"5728","type":"CID","arg1_id":"5719","arg2_id":"5716","normalized":[]},{"id":"5729","type":"CID","arg1_id":"5719","arg2_id":"5718","normalized":[]},{"id":"5730","type":"CID","arg1_id":"5719","arg2_id":"5722","normalized":[]},{"id":"5731","type":"CID","arg1_id":"5719","arg2_id":"5723","normalized":[]},{"id":"5732","type":"CID","arg1_id":"5721","arg2_id":"5716","normalized":[]},{"id":"5733","type":"CID","arg1_id":"5721","arg2_id":"5718","normalized":[]},{"id":"5734","type":"CID","arg1_id":"5721","arg2_id":"5722","normalized":[]},{"id":"5735","type":"CID","arg1_id":"5721","arg2_id":"5723","normalized":[]}]}
{"id":"5736","document_id":"7083920","passages":[{"id":"5737","type":"title","text":["Further observations on the electrophysiologic effects of oral amiodarone therapy."],"offsets":[[0,82]]},{"id":"5738","type":"abstract","text":["A case is presented of a reversible intra-Hisian block occurring under amiodarone treatment for atrial tachycardia in a patient without clear intraventricular conduction abnormalities. His bundle recordings showed an atrial tachycardia with intermittent exit block and greatly prolonged BH and HV intervals (40 and 100 msec, respectively). Thirty days after amiodarone discontinuation, His bundle electrograms showed atrial flutter without intra-Hisian or infra-Hisian delay. Amiodarone should be used with caution during long-term oral therapy in patients with or without clear intraventricular conduction defects."],"offsets":[[83,698]]}],"entities":[{"id":"5739","type":"Chemical","text":["amiodarone"],"offsets":[[63,73]],"normalized":[{"db_name":"MESH","db_id":"D000638"}]},{"id":"5740","type":"Disease","text":["intra-Hisian block"],"offsets":[[119,137]],"normalized":[{"db_name":"MESH","db_id":"D006327"}]},{"id":"5741","type":"Chemical","text":["amiodarone"],"offsets":[[154,164]],"normalized":[{"db_name":"MESH","db_id":"D000638"}]},{"id":"5742","type":"Disease","text":["atrial tachycardia"],"offsets":[[179,197]],"normalized":[{"db_name":"MESH","db_id":"D013617"}]},{"id":"5743","type":"Disease","text":["intraventricular conduction abnormalities"],"offsets":[[225,266]],"normalized":[{"db_name":"MESH","db_id":"D006345"}]},{"id":"5744","type":"Disease","text":["atrial tachycardia"],"offsets":[[300,318]],"normalized":[{"db_name":"MESH","db_id":"D013617"}]},{"id":"5745","type":"Chemical","text":["amiodarone"],"offsets":[[441,451]],"normalized":[{"db_name":"MESH","db_id":"D000638"}]},{"id":"5746","type":"Disease","text":["atrial flutter"],"offsets":[[500,514]],"normalized":[{"db_name":"MESH","db_id":"D001282"}]},{"id":"5747","type":"Chemical","text":["Amiodarone"],"offsets":[[559,569]],"normalized":[{"db_name":"MESH","db_id":"D000638"}]}],"events":[],"coreferences":[],"relations":[{"id":"5748","type":"CID","arg1_id":"5739","arg2_id":"5740","normalized":[]},{"id":"5749","type":"CID","arg1_id":"5741","arg2_id":"5740","normalized":[]},{"id":"5750","type":"CID","arg1_id":"5745","arg2_id":"5740","normalized":[]},{"id":"5751","type":"CID","arg1_id":"5747","arg2_id":"5740","normalized":[]}]}
{"id":"5752","document_id":"7269015","passages":[{"id":"5753","type":"title","text":["Busulfan-induced hemorrhagic cystitis."],"offsets":[[0,38]]},{"id":"5754","type":"abstract","text":["A case of a busulfan-induced hemorrhage cystitis is reported. Spontaneous resolution occurred following cessation of the drug. The similarity between the histologic appearances of busulfan cystitis and both radiation and cyclophosphamide-induced cystitis is discussed and the world literature reviewed. In view of the known tendency of busulfan to induce cellular atypia and carcinoma in other sites, periodic urinary cytology is suggested in patients on long-term therapy."],"offsets":[[39,512]]}],"entities":[{"id":"5755","type":"Chemical","text":["Busulfan"],"offsets":[[0,8]],"normalized":[{"db_name":"MESH","db_id":"D002066"}]},{"id":"5756","type":"Disease","text":["hemorrhagic cystitis"],"offsets":[[17,37]],"normalized":[{"db_name":"MESH","db_id":"D006470"},{"db_name":"MESH","db_id":"D003556"}]},{"id":"5757","type":"Disease","text":["hemorrhagic"],"offsets":[[17,28]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"5758","type":"Disease","text":["cystitis"],"offsets":[[29,37]],"normalized":[{"db_name":"MESH","db_id":"D003556"}]},{"id":"5759","type":"Chemical","text":["busulfan"],"offsets":[[51,59]],"normalized":[{"db_name":"MESH","db_id":"D002066"}]},{"id":"5760","type":"Disease","text":["hemorrhage cystitis"],"offsets":[[68,87]],"normalized":[{"db_name":"MESH","db_id":"D006470"},{"db_name":"MESH","db_id":"D003556"}]},{"id":"5761","type":"Disease","text":["hemorrhage"],"offsets":[[68,78]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"5762","type":"Disease","text":["cystitis"],"offsets":[[79,87]],"normalized":[{"db_name":"MESH","db_id":"D003556"}]},{"id":"5763","type":"Chemical","text":["busulfan"],"offsets":[[219,227]],"normalized":[{"db_name":"MESH","db_id":"D002066"}]},{"id":"5764","type":"Disease","text":["cystitis"],"offsets":[[228,236]],"normalized":[{"db_name":"MESH","db_id":"D003556"}]},{"id":"5765","type":"Chemical","text":["cyclophosphamide"],"offsets":[[260,276]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"5766","type":"Disease","text":["cystitis"],"offsets":[[285,293]],"normalized":[{"db_name":"MESH","db_id":"D003556"}]},{"id":"5767","type":"Chemical","text":["busulfan"],"offsets":[[375,383]],"normalized":[{"db_name":"MESH","db_id":"D002066"}]},{"id":"5768","type":"Disease","text":["carcinoma"],"offsets":[[414,423]],"normalized":[{"db_name":"MESH","db_id":"D002277"}]}],"events":[],"coreferences":[],"relations":[{"id":"5769","type":"CID","arg1_id":"5755","arg2_id":"5756","normalized":[]},{"id":"5770","type":"CID","arg1_id":"5755","arg2_id":"5758","normalized":[]},{"id":"5771","type":"CID","arg1_id":"5755","arg2_id":"5760","normalized":[]},{"id":"5772","type":"CID","arg1_id":"5755","arg2_id":"5762","normalized":[]},{"id":"5773","type":"CID","arg1_id":"5755","arg2_id":"5764","normalized":[]},{"id":"5774","type":"CID","arg1_id":"5755","arg2_id":"5766","normalized":[]},{"id":"5775","type":"CID","arg1_id":"5759","arg2_id":"5756","normalized":[]},{"id":"5776","type":"CID","arg1_id":"5759","arg2_id":"5758","normalized":[]},{"id":"5777","type":"CID","arg1_id":"5759","arg2_id":"5760","normalized":[]},{"id":"5778","type":"CID","arg1_id":"5759","arg2_id":"5762","normalized":[]},{"id":"5779","type":"CID","arg1_id":"5759","arg2_id":"5764","normalized":[]},{"id":"5780","type":"CID","arg1_id":"5759","arg2_id":"5766","normalized":[]},{"id":"5781","type":"CID","arg1_id":"5763","arg2_id":"5756","normalized":[]},{"id":"5782","type":"CID","arg1_id":"5763","arg2_id":"5758","normalized":[]},{"id":"5783","type":"CID","arg1_id":"5763","arg2_id":"5760","normalized":[]},{"id":"5784","type":"CID","arg1_id":"5763","arg2_id":"5762","normalized":[]},{"id":"5785","type":"CID","arg1_id":"5763","arg2_id":"5764","normalized":[]},{"id":"5786","type":"CID","arg1_id":"5763","arg2_id":"5766","normalized":[]},{"id":"5787","type":"CID","arg1_id":"5767","arg2_id":"5756","normalized":[]},{"id":"5788","type":"CID","arg1_id":"5767","arg2_id":"5758","normalized":[]},{"id":"5789","type":"CID","arg1_id":"5767","arg2_id":"5760","normalized":[]},{"id":"5790","type":"CID","arg1_id":"5767","arg2_id":"5762","normalized":[]},{"id":"5791","type":"CID","arg1_id":"5767","arg2_id":"5764","normalized":[]},{"id":"5792","type":"CID","arg1_id":"5767","arg2_id":"5766","normalized":[]},{"id":"5793","type":"CID","arg1_id":"5755","arg2_id":"5756","normalized":[]},{"id":"5794","type":"CID","arg1_id":"5755","arg2_id":"5757","normalized":[]},{"id":"5795","type":"CID","arg1_id":"5755","arg2_id":"5760","normalized":[]},{"id":"5796","type":"CID","arg1_id":"5755","arg2_id":"5761","normalized":[]},{"id":"5797","type":"CID","arg1_id":"5759","arg2_id":"5756","normalized":[]},{"id":"5798","type":"CID","arg1_id":"5759","arg2_id":"5757","normalized":[]},{"id":"5799","type":"CID","arg1_id":"5759","arg2_id":"5760","normalized":[]},{"id":"5800","type":"CID","arg1_id":"5759","arg2_id":"5761","normalized":[]},{"id":"5801","type":"CID","arg1_id":"5763","arg2_id":"5756","normalized":[]},{"id":"5802","type":"CID","arg1_id":"5763","arg2_id":"5757","normalized":[]},{"id":"5803","type":"CID","arg1_id":"5763","arg2_id":"5760","normalized":[]},{"id":"5804","type":"CID","arg1_id":"5763","arg2_id":"5761","normalized":[]},{"id":"5805","type":"CID","arg1_id":"5767","arg2_id":"5756","normalized":[]},{"id":"5806","type":"CID","arg1_id":"5767","arg2_id":"5757","normalized":[]},{"id":"5807","type":"CID","arg1_id":"5767","arg2_id":"5760","normalized":[]},{"id":"5808","type":"CID","arg1_id":"5767","arg2_id":"5761","normalized":[]}]}
{"id":"5809","document_id":"7352670","passages":[{"id":"5810","type":"title","text":["Rebound hypertensive after sodium nitroprusside prevented by saralasin in rats."],"offsets":[[0,79]]},{"id":"5811","type":"abstract","text":["The role of the renin--angiotensin system in the maintenance of blood pressure during halothane anesthesia and sodium nitroprusside (SNP)-induced hypotension was evaluated. Control rats received halothane anesthesia (1 MAC) for one hour, followed by SNP infusion, 40 microgram\/kg\/min, for 30 min, followed by a 30-min recovery period. A second group of rats was treated identically and, in addition, received an infusion of saralasin (a competitive inhibitor of angiotensin II) throughout the experimental period. In each group, SNP infusion resulted in an initial decrease in blood pressure from 86 torr and 83 torr, respectively, to 48 torr. During the SNP infusion the control animals demonstrated a progressive increase in blood pressure to 61 torr, whereas the saralasin-treated animals showed no change. Following discontinuation of SNP, blood pressure in the control animals rebounded to 94 torr, as compared with 78 torr in the saralasin-treated rats. This study indicates that with stable halothane anesthesia, the partial recovery of blood pressure during SNP infusion and the post-SNP rebound of blood pressure can be completely blocked by saralasin. This demonstrates the participation of the renin--angiotensin system in antagonizing the combined hypotensive effects of halothane and SNP."],"offsets":[[80,1381]]}],"entities":[{"id":"5812","type":"Disease","text":["hypertensive"],"offsets":[[8,20]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"5813","type":"Chemical","text":["sodium nitroprusside"],"offsets":[[27,47]],"normalized":[{"db_name":"MESH","db_id":"D009599"}]},{"id":"5814","type":"Chemical","text":["saralasin"],"offsets":[[61,70]],"normalized":[{"db_name":"MESH","db_id":"D012504"}]},{"id":"5815","type":"Chemical","text":["angiotensin"],"offsets":[[103,114]],"normalized":[{"db_name":"MESH","db_id":"D000809"}]},{"id":"5816","type":"Chemical","text":["halothane"],"offsets":[[166,175]],"normalized":[{"db_name":"MESH","db_id":"D006221"}]},{"id":"5817","type":"Chemical","text":["sodium nitroprusside"],"offsets":[[191,211]],"normalized":[{"db_name":"MESH","db_id":"D009599"}]},{"id":"5818","type":"Chemical","text":["SNP"],"offsets":[[213,216]],"normalized":[{"db_name":"MESH","db_id":"D009599"}]},{"id":"5819","type":"Disease","text":["hypotension"],"offsets":[[226,237]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"5820","type":"Chemical","text":["halothane"],"offsets":[[275,284]],"normalized":[{"db_name":"MESH","db_id":"D006221"}]},{"id":"5821","type":"Chemical","text":["SNP"],"offsets":[[330,333]],"normalized":[{"db_name":"MESH","db_id":"D009599"}]},{"id":"5822","type":"Chemical","text":["saralasin"],"offsets":[[504,513]],"normalized":[{"db_name":"MESH","db_id":"D012504"}]},{"id":"5823","type":"Chemical","text":["angiotensin II"],"offsets":[[542,556]],"normalized":[{"db_name":"MESH","db_id":"D000804"}]},{"id":"5824","type":"Chemical","text":["SNP"],"offsets":[[609,612]],"normalized":[{"db_name":"MESH","db_id":"D009599"}]},{"id":"5825","type":"Chemical","text":["SNP"],"offsets":[[735,738]],"normalized":[{"db_name":"MESH","db_id":"D009599"}]},{"id":"5826","type":"Disease","text":["increase in blood pressure"],"offsets":[[795,821]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"5827","type":"Chemical","text":["saralasin"],"offsets":[[846,855]],"normalized":[{"db_name":"MESH","db_id":"D012504"}]},{"id":"5828","type":"Chemical","text":["SNP"],"offsets":[[919,922]],"normalized":[{"db_name":"MESH","db_id":"D009599"}]},{"id":"5829","type":"Chemical","text":["saralasin"],"offsets":[[1016,1025]],"normalized":[{"db_name":"MESH","db_id":"D012504"}]},{"id":"5830","type":"Chemical","text":["halothane"],"offsets":[[1078,1087]],"normalized":[{"db_name":"MESH","db_id":"D006221"}]},{"id":"5831","type":"Chemical","text":["SNP"],"offsets":[[1146,1149]],"normalized":[{"db_name":"MESH","db_id":"D009599"}]},{"id":"5832","type":"Chemical","text":["SNP"],"offsets":[[1172,1175]],"normalized":[{"db_name":"MESH","db_id":"D009599"}]},{"id":"5833","type":"Chemical","text":["saralasin"],"offsets":[[1231,1240]],"normalized":[{"db_name":"MESH","db_id":"D012504"}]},{"id":"5834","type":"Chemical","text":["angiotensin"],"offsets":[[1292,1303]],"normalized":[{"db_name":"MESH","db_id":"D000809"}]},{"id":"5835","type":"Disease","text":["hypotensive"],"offsets":[[1340,1351]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"5836","type":"Chemical","text":["halothane"],"offsets":[[1363,1372]],"normalized":[{"db_name":"MESH","db_id":"D006221"}]},{"id":"5837","type":"Chemical","text":["SNP"],"offsets":[[1377,1380]],"normalized":[{"db_name":"MESH","db_id":"D009599"}]}],"events":[],"coreferences":[],"relations":[{"id":"5838","type":"CID","arg1_id":"5813","arg2_id":"5819","normalized":[]},{"id":"5839","type":"CID","arg1_id":"5813","arg2_id":"5835","normalized":[]},{"id":"5840","type":"CID","arg1_id":"5817","arg2_id":"5819","normalized":[]},{"id":"5841","type":"CID","arg1_id":"5817","arg2_id":"5835","normalized":[]},{"id":"5842","type":"CID","arg1_id":"5818","arg2_id":"5819","normalized":[]},{"id":"5843","type":"CID","arg1_id":"5818","arg2_id":"5835","normalized":[]},{"id":"5844","type":"CID","arg1_id":"5821","arg2_id":"5819","normalized":[]},{"id":"5845","type":"CID","arg1_id":"5821","arg2_id":"5835","normalized":[]},{"id":"5846","type":"CID","arg1_id":"5824","arg2_id":"5819","normalized":[]},{"id":"5847","type":"CID","arg1_id":"5824","arg2_id":"5835","normalized":[]},{"id":"5848","type":"CID","arg1_id":"5825","arg2_id":"5819","normalized":[]},{"id":"5849","type":"CID","arg1_id":"5825","arg2_id":"5835","normalized":[]},{"id":"5850","type":"CID","arg1_id":"5828","arg2_id":"5819","normalized":[]},{"id":"5851","type":"CID","arg1_id":"5828","arg2_id":"5835","normalized":[]},{"id":"5852","type":"CID","arg1_id":"5831","arg2_id":"5819","normalized":[]},{"id":"5853","type":"CID","arg1_id":"5831","arg2_id":"5835","normalized":[]},{"id":"5854","type":"CID","arg1_id":"5832","arg2_id":"5819","normalized":[]},{"id":"5855","type":"CID","arg1_id":"5832","arg2_id":"5835","normalized":[]},{"id":"5856","type":"CID","arg1_id":"5837","arg2_id":"5819","normalized":[]},{"id":"5857","type":"CID","arg1_id":"5837","arg2_id":"5835","normalized":[]},{"id":"5858","type":"CID","arg1_id":"5816","arg2_id":"5819","normalized":[]},{"id":"5859","type":"CID","arg1_id":"5816","arg2_id":"5835","normalized":[]},{"id":"5860","type":"CID","arg1_id":"5820","arg2_id":"5819","normalized":[]},{"id":"5861","type":"CID","arg1_id":"5820","arg2_id":"5835","normalized":[]},{"id":"5862","type":"CID","arg1_id":"5830","arg2_id":"5819","normalized":[]},{"id":"5863","type":"CID","arg1_id":"5830","arg2_id":"5835","normalized":[]},{"id":"5864","type":"CID","arg1_id":"5836","arg2_id":"5819","normalized":[]},{"id":"5865","type":"CID","arg1_id":"5836","arg2_id":"5835","normalized":[]}]}
{"id":"5866","document_id":"7504976","passages":[{"id":"5867","type":"title","text":["Toxic hepatitis induced by antithyroid drugs: four cases including one with cross-reactivity between carbimazole and benzylthiouracil."],"offsets":[[0,134]]},{"id":"5868","type":"abstract","text":["OBJECTIVE: This study was conducted to assess the occurrence of hepatic adverse effects encountered with antithyroid drugs. METHODS: Retrospective review of medical records of 236 patients with hyperthyroidism admitted in our department (in- or out-patients) from 1986 to 1992. RESULTS: Four patients (1.7%) were identified with toxic hepatitis which could reasonably be attributed to the use of antithyroid agent. Two patients had a cholestatic hepatitis induced by carbimazole (N  omercazole). Two others had a mixed (cholestatic and cytolytic) hepatitis following carbimazole. One of the latter two patients further experienced a cytolytic hepatitis which appeared after Benzylthiouracil (Basd  ne) had replaced carbimazole. Biological features of hepatitis disappeared in all cases after cessation of the incriminated drug, while biliary, viral and immunological searches were negative. Only 2 patients of our retrospective study experienced a mild or severe neutropenia. CONCLUSION: Toxic hepatitis is a potential adverse effect of antithyroid drugs which warrants, as for haematological disturbances, a pre-therapeutic determination and a careful follow-up of relevant biological markers. Moreover, hepatotoxicity may not be restricted to one class of antithyroid agents."],"offsets":[[135,1412]]}],"entities":[{"id":"5869","type":"Disease","text":["Toxic hepatitis"],"offsets":[[0,15]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"5870","type":"Chemical","text":["carbimazole"],"offsets":[[101,112]],"normalized":[{"db_name":"MESH","db_id":"D002231"}]},{"id":"5871","type":"Chemical","text":["benzylthiouracil"],"offsets":[[117,133]],"normalized":[{"db_name":"MESH","db_id":"C019269"}]},{"id":"5872","type":"Disease","text":["hepatic adverse effects"],"offsets":[[199,222]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"5873","type":"Disease","text":["hyperthyroidism"],"offsets":[[329,344]],"normalized":[{"db_name":"MESH","db_id":"D006980"}]},{"id":"5874","type":"Disease","text":["toxic hepatitis"],"offsets":[[464,479]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"5875","type":"Disease","text":["cholestatic hepatitis"],"offsets":[[569,590]],"normalized":[{"db_name":"MESH","db_id":"D002779"},{"db_name":"MESH","db_id":"D056486"}]},{"id":"5876","type":"Disease","text":["cholestatic"],"offsets":[[569,580]],"normalized":[{"db_name":"MESH","db_id":"D002779"}]},{"id":"5877","type":"Disease","text":["hepatitis"],"offsets":[[581,590]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"5878","type":"Chemical","text":["carbimazole"],"offsets":[[602,613]],"normalized":[{"db_name":"MESH","db_id":"D002231"}]},{"id":"5879","type":"Chemical","text":["N  omercazole"],"offsets":[[615,628]],"normalized":[{"db_name":"MESH","db_id":"D002231"}]},{"id":"5880","type":"Disease","text":["cholestatic"],"offsets":[[655,666]],"normalized":[{"db_name":"MESH","db_id":"D002779"}]},{"id":"5881","type":"Disease","text":["hepatitis"],"offsets":[[682,691]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"5882","type":"Chemical","text":["carbimazole"],"offsets":[[702,713]],"normalized":[{"db_name":"MESH","db_id":"D002231"}]},{"id":"5883","type":"Disease","text":["hepatitis"],"offsets":[[778,787]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"5884","type":"Chemical","text":["Benzylthiouracil"],"offsets":[[809,825]],"normalized":[{"db_name":"MESH","db_id":"C019269"}]},{"id":"5885","type":"Chemical","text":["Basd  ne"],"offsets":[[827,835]],"normalized":[{"db_name":"MESH","db_id":"C019269"}]},{"id":"5886","type":"Chemical","text":["carbimazole"],"offsets":[[850,861]],"normalized":[{"db_name":"MESH","db_id":"D002231"}]},{"id":"5887","type":"Disease","text":["hepatitis"],"offsets":[[886,895]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"5888","type":"Disease","text":["neutropenia"],"offsets":[[1098,1109]],"normalized":[{"db_name":"MESH","db_id":"D009503"}]},{"id":"5889","type":"Disease","text":["Toxic 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{"id":"5956","document_id":"7628595","passages":[{"id":"5957","type":"title","text":["Study of the role of vitamin B12 and folinic acid supplementation in preventing hematologic toxicity of zidovudine."],"offsets":[[0,115]]},{"id":"5958","type":"abstract","text":["A prospective, randomized study was conducted to evaluate the role of vitamin B12 and folinic acid supplementation in preventing zidovudine (ZDV)-induced bone marrow suppression. Seventy-five human immunodeficiency virus (HIV)-infected patients with CD4+ cell counts < 500\/mm3 were randomized to receive either ZDV (500 mg daily) alone (group I, n = 38) or in combination with folinic acid (15 mg daily) and intramascular vitamin B12 (1000 micrograms monthly) (group II, n = 37). Finally, 15 patients were excluded from the study (noncompliance 14, death 1); thus, 60 patients (31 in group I and 29 in group II) were eligible for analysis. No significant differences between groups were found at enrollment. During the study, vitamin B12 and folate levels were significantly higher in group II patients; however, no differences in hemoglobin, hematocrit, mean corpuscular volume, and white-cell, neutrophil and platelet counts were observed between groups at 3, 6, 9 and 12 months. Severe hematologic toxicity (neutrophil count < 1000\/mm3 and\/or hemoglobin < 8 g\/dl) occurred in 4 patients assigned to group I and 7 assigned to group II. There was no correlation between vitamin B12 or folate levels and development of myelosuppression. Vitamin B12 and folinic acid supplementation of ZDV therapy does not seem useful in preventing or reducing ZDV-induced myelotoxicity in the overall treated population, although a beneficial effect in certain subgroups of patients cannot be excluded."],"offsets":[[116,1602]]}],"entities":[{"id":"5959","type":"Chemical","text":["vitamin B12"],"offsets":[[21,32]],"normalized":[{"db_name":"MESH","db_id":"D014805"}]},{"id":"5960","type":"Chemical","text":["folinic acid"],"offsets":[[37,49]],"normalized":[{"db_name":"MESH","db_id":"D002955"}]},{"id":"5961","type":"Disease","text":["toxicity"],"offsets":[[92,100]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"5962","type":"Chemical","text":["zidovudine"],"offsets":[[104,114]],"normalized":[{"db_name":"MESH","db_id":"D015215"}]},{"id":"5963","type":"Chemical","text":["vitamin B12"],"offsets":[[186,197]],"normalized":[{"db_name":"MESH","db_id":"D014805"}]},{"id":"5964","type":"Chemical","text":["folinic acid"],"offsets":[[202,214]],"normalized":[{"db_name":"MESH","db_id":"D002955"}]},{"id":"5965","type":"Chemical","text":["zidovudine"],"offsets":[[245,255]],"normalized":[{"db_name":"MESH","db_id":"D015215"}]},{"id":"5966","type":"Chemical","text":["ZDV"],"offsets":[[257,260]],"normalized":[{"db_name":"MESH","db_id":"D015215"}]},{"id":"5967","type":"Disease","text":["bone marrow suppression"],"offsets":[[270,293]],"normalized":[{"db_name":"MESH","db_id":"D001855"}]},{"id":"5968","type":"Disease","text":["human immunodeficiency virus (HIV)-infected"],"offsets":[[308,351]],"normalized":[{"db_name":"MESH","db_id":"D015658"}]},{"id":"5969","type":"Chemical","text":["ZDV"],"offsets":[[427,430]],"normalized":[{"db_name":"MESH","db_id":"D015215"}]},{"id":"5970","type":"Chemical","text":["folinic acid"],"offsets":[[493,505]],"normalized":[{"db_name":"MESH","db_id":"D002955"}]},{"id":"5971","type":"Chemical","text":["vitamin B12"],"offsets":[[538,549]],"normalized":[{"db_name":"MESH","db_id":"D014805"}]},{"id":"5972","type":"Disease","text":["death"],"offsets":[[665,670]],"normalized":[{"db_name":"MESH","db_id":"D003643"}]},{"id":"5973","type":"Chemical","text":["vitamin B12"],"offsets":[[842,853]],"normalized":[{"db_name":"MESH","db_id":"D014805"}]},{"id":"5974","type":"Chemical","text":["folate"],"offsets":[[858,864]],"normalized":[{"db_name":"MESH","db_id":"D005492"}]},{"id":"5975","type":"Disease","text":["toxicity"],"offsets":[[1117,1125]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"5976","type":"Chemical","text":["vitamin B12"],"offsets":[[1287,1298]],"normalized":[{"db_name":"MESH","db_id":"D014805"}]},{"id":"5977","type":"Chemical","text":["folate"],"offsets":[[1302,1308]],"normalized":[{"db_name":"MESH","db_id":"D005492"}]},{"id":"5978","type":"Disease","text":["myelosuppression"],"offsets":[[1335,1351]],"normalized":[{"db_name":"MESH","db_id":"D001855"}]},{"id":"5979","type":"Chemical","text":["Vitamin B12"],"offsets":[[1353,1364]],"normalized":[{"db_name":"MESH","db_id":"D014805"}]},{"id":"5980","type":"Chemical","text":["folinic acid"],"offsets":[[1369,1381]],"normalized":[{"db_name":"MESH","db_id":"D002955"}]},{"id":"5981","type":"Chemical","text":["ZDV"],"offsets":[[1401,1404]],"normalized":[{"db_name":"MESH","db_id":"D015215"}]},{"id":"5982","type":"Chemical","text":["ZDV"],"offsets":[[1460,1463]],"normalized":[{"db_name":"MESH","db_id":"D015215"}]},{"id":"5983","type":"Disease","text":["myelotoxicity"],"offsets":[[1472,1485]],"normalized":[{"db_name":"MESH","db_id":"D001855"}]}],"events":[],"coreferences":[],"relations":[{"id":"5984","type":"CID","arg1_id":"5962","arg2_id":"5967","normalized":[]},{"id":"5985","type":"CID","arg1_id":"5962","arg2_id":"5978","normalized":[]},{"id":"5986","type":"CID","arg1_id":"5962","arg2_id":"5983","normalized":[]},{"id":"5987","type":"CID","arg1_id":"5965","arg2_id":"5967","normalized":[]},{"id":"5988","type":"CID","arg1_id":"5965","arg2_id":"5978","normalized":[]},{"id":"5989","type":"CID","arg1_id":"5965","arg2_id":"5983","normalized":[]},{"id":"5990","type":"CID","arg1_id":"5966","arg2_id":"5967","normalized":[]},{"id":"5991","type":"CID","arg1_id":"5966","arg2_id":"5978","normalized":[]},{"id":"5992","type":"CID","arg1_id":"5966","arg2_id":"5983","normalized":[]},{"id":"5993","type":"CID","arg1_id":"5969","arg2_id":"5967","normalized":[]},{"id":"5994","type":"CID","arg1_id":"5969","arg2_id":"5978","normalized":[]},{"id":"5995","type":"CID","arg1_id":"5969","arg2_id":"5983","normalized":[]},{"id":"5996","type":"CID","arg1_id":"5981","arg2_id":"5967","normalized":[]},{"id":"5997","type":"CID","arg1_id":"5981","arg2_id":"5978","normalized":[]},{"id":"5998","type":"CID","arg1_id":"5981","arg2_id":"5983","normalized":[]},{"id":"5999","type":"CID","arg1_id":"5982","arg2_id":"5967","normalized":[]},{"id":"6000","type":"CID","arg1_id":"5982","arg2_id":"5978","normalized":[]},{"id":"6001","type":"CID","arg1_id":"5982","arg2_id":"5983","normalized":[]}]}
{"id":"6002","document_id":"7858459","passages":[{"id":"6003","type":"title","text":["Acute confusion induced by a high-dose infusion of 5-fluorouracil and folinic acid."],"offsets":[[0,83]]},{"id":"6004","type":"abstract","text":["A 61-year-old man was treated with combination chemotherapy incorporating cisplatinum, etoposide, high-dose 5-fluorouracil (2,250 mg\/m2\/24 hours) and folinic acid for an inoperable gastric adenocarcinoma. He developed acute neurologic symptoms of mental confusion, disorientation and irritability, and then lapsed into a deep coma, lasting for approximately 40 hours during the first dose (day 2) of 5-fluorouracil and folinic acid infusion. This complication reappeared on day 25 during the second dose of 5-fluorouracil and folinic acid, which were then the only drugs given. Because folinic acid was unlikely to be associated with this condition, neurotoxicity due to high-dose 5-fluorouracil was highly suspected. The pathogenesis of 5-fluorouracil neurotoxicity may be due to a Krebs cycle blockade by fluoroacetate and fluorocitrate, thiamine deficiency, or dihydrouracil dehydrogenase deficiency. High-dose 5-fluorouracil\/folinic acid infusion therapy has recently become a popular regimen for various cancers. It is necessary that both oncologists and neurologists be fully aware of this unusual complication."],"offsets":[[84,1201]]}],"entities":[{"id":"6005","type":"Disease","text":["confusion"],"offsets":[[6,15]],"normalized":[{"db_name":"MESH","db_id":"D003221"}]},{"id":"6006","type":"Chemical","text":["5-fluorouracil"],"offsets":[[51,65]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"6007","type":"Chemical","text":["folinic acid"],"offsets":[[70,82]],"normalized":[{"db_name":"MESH","db_id":"D002955"}]},{"id":"6008","type":"Chemical","text":["cisplatinum"],"offsets":[[158,169]],"normalized":[{"db_name":"MESH","db_id":"D002945"}]},{"id":"6009","type":"Chemical","text":["etoposide"],"offsets":[[171,180]],"normalized":[{"db_name":"MESH","db_id":"D005047"}]},{"id":"6010","type":"Chemical","text":["5-fluorouracil"],"offsets":[[192,206]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"6011","type":"Chemical","text":["folinic 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{"id":"6085","document_id":"7862923","passages":[{"id":"6086","type":"title","text":["Effect of switching carbamazepine to oxcarbazepine on the plasma levels of neuroleptics. A case report."],"offsets":[[0,103]]},{"id":"6087","type":"abstract","text":["Carbamazepine was switched to its 10-keto analogue oxcarbazepine among six difficult-to-treat schizophrenic or organic psychotic patients using concomitantly haloperidol, chlorpromazine or clozapine. This change resulted within 2-4 weeks in the 50-200% increase in the plasma levels of these neuroleptics and the appearance of extrapyramidal symptoms. None of the patients showed any clinical deteriotation during the following 3-6 months. The results of this case report support the idea that in contrast with carbamazepine oxcarbazepine does not induce the hepatic microsomal enzyme systems regulating the inactivation of antipsychotic drugs."],"offsets":[[104,748]]}],"entities":[{"id":"6088","type":"Chemical","text":["carbamazepine"],"offsets":[[20,33]],"normalized":[{"db_name":"MESH","db_id":"D002220"}]},{"id":"6089","type":"Chemical","text":["oxcarbazepine"],"offsets":[[37,50]],"normalized":[{"db_name":"MESH","db_id":"C036006"}]},{"id":"6090","type":"Chemical","text":["Carbamazepine"],"offsets":[[104,117]],"normalized":[{"db_name":"MESH","db_id":"D002220"}]},{"id":"6091","type":"Chemical","text":["oxcarbazepine"],"offsets":[[155,168]],"normalized":[{"db_name":"MESH","db_id":"C036006"}]},{"id":"6092","type":"Disease","text":["schizophrenic"],"offsets":[[198,211]],"normalized":[{"db_name":"MESH","db_id":"D012559"}]},{"id":"6093","type":"Disease","text":["organic psychotic"],"offsets":[[215,232]],"normalized":[{"db_name":"MESH","db_id":"D019965"}]},{"id":"6094","type":"Chemical","text":["haloperidol"],"offsets":[[262,273]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"6095","type":"Chemical","text":["chlorpromazine"],"offsets":[[275,289]],"normalized":[{"db_name":"MESH","db_id":"D002746"}]},{"id":"6096","type":"Chemical","text":["clozapine"],"offsets":[[293,302]],"normalized":[{"db_name":"MESH","db_id":"D003024"}]},{"id":"6097","type":"Disease","text":["extrapyramidal symptoms"],"offsets":[[431,454]],"normalized":[{"db_name":"MESH","db_id":"D001480"}]},{"id":"6098","type":"Chemical","text":["carbamazepine"],"offsets":[[615,628]],"normalized":[{"db_name":"MESH","db_id":"D002220"}]},{"id":"6099","type":"Chemical","text":["oxcarbazepine"],"offsets":[[629,642]],"normalized":[{"db_name":"MESH","db_id":"C036006"}]}],"events":[],"coreferences":[],"relations":[{"id":"6100","type":"CID","arg1_id":"6094","arg2_id":"6097","normalized":[]},{"id":"6101","type":"CID","arg1_id":"6095","arg2_id":"6097","normalized":[]},{"id":"6102","type":"CID","arg1_id":"6096","arg2_id":"6097","normalized":[]},{"id":"6103","type":"CID","arg1_id":"6089","arg2_id":"6097","normalized":[]},{"id":"6104","type":"CID","arg1_id":"6091","arg2_id":"6097","normalized":[]},{"id":"6105","type":"CID","arg1_id":"6099","arg2_id":"6097","normalized":[]}]}
{"id":"6106","document_id":"7919560","passages":[{"id":"6107","type":"title","text":["Erythema multiforme and hypersensitivity myocarditis caused by ampicillin."],"offsets":[[0,74]]},{"id":"6108","type":"abstract","text":["OBJECTIVE: To report a case of erythema multiforme and hypersensitivity myocarditis caused by ampicillin. CASE SUMMARY: A 13-year-old boy was treated with ampicillin and gentamicin because of suspected septicemia. Medications were discontinued when erythema multiforme and congestive heart failure caused by myocarditis occurred. The patient was treated with methylprednisolone and gradually improved. Macrophage-migration inhibition (MIF) test with ampicillin was positive. DISCUSSION: After most infections causing erythema multiforme and myocarditis were ruled out, a drug-induced allergic reaction was suspected. Positive MIF test for ampicillin showed sensitization of the patient's lymphocytes to ampicillin. CONCLUSIONS: Hypersensitivity myocarditis is a rare and dangerous manifestation of allergy to penicillins."],"offsets":[[75,896]]}],"entities":[{"id":"6109","type":"Disease","text":["Erythema multiforme"],"offsets":[[0,19]],"normalized":[{"db_name":"MESH","db_id":"D004892"}]},{"id":"6110","type":"Disease","text":["hypersensitivity myocarditis"],"offsets":[[24,52]],"normalized":[{"db_name":"MESH","db_id":"D009205"}]},{"id":"6111","type":"Chemical","text":["ampicillin"],"offsets":[[63,73]],"normalized":[{"db_name":"MESH","db_id":"D000667"}]},{"id":"6112","type":"Disease","text":["erythema multiforme"],"offsets":[[106,125]],"normalized":[{"db_name":"MESH","db_id":"D004892"}]},{"id":"6113","type":"Disease","text":["hypersensitivity 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{"id":"6198","document_id":"8092427","passages":[{"id":"6199","type":"title","text":["Immediate allergic reactions to amoxicillin."],"offsets":[[0,44]]},{"id":"6200","type":"abstract","text":["A large group of patients with suspected allergic reactions to beta-lactam antibiotics was evaluated. A detailed clinical history, together with skin tests, RAST (radioallergosorbent test), and controlled challenge tests, was used to establish whether patients allergic to beta-lactam antibiotics had selective immediate allergic responses to amoxicillin (AX) or were cross-reacting with other penicillin derivatives. Skin tests were performed with benzylpenicilloyl-poly-L-lysine (BPO-PLL), benzylpenicilloate, benzylpenicillin (PG), ampicillin (AMP), and AX. RAST for BPO-PLL and AX-PLL was done. When both skin test and RAST for BPO were negative, single-blind, placebo-controlled challenge tests were done to ensure tolerance of PG or sensitivity to AX. A total of 177 patients were diagnosed as allergic to beta-lactam antibiotics. We selected the 54 (30.5%) cases of immediate AX allergy with good tolerance of PG. Anaphylaxis was seen in 37 patients (69%), the other 17 (31%) having urticaria and\/or angioedema. All the patients were skin test negative to BPO; 49 of 51 (96%) were also negative to MDM, and 44 of 46 (96%) to PG. Skin tests with AX were positive in 34 (63%) patients. RAST was positive for AX in 22 patients (41%) and to BPO in just 5 (9%). None of the sera with negative RAST for AX were positive to BPO. Challenge tests with AX were performed in 23 subjects (43%) to establish the diagnosis of immediate allergic reaction to AX, and in 15 cases (28%) both skin test and RAST for AX were negative. PG was well tolerated by all 54 patients. We describe the largest group of AX-allergic patients who have tolerated PG reported so far. Diagnosis of these patients can be achieved only if specific AX-related reagents are employed. Further studies are necessary to determine the exact extent of this problem and to improve the efficacy of diagnostic methods."],"offsets":[[45,1923]]}],"entities":[{"id":"6201","type":"Disease","text":["allergic reactions"],"offsets":[[10,28]],"normalized":[{"db_name":"MESH","db_id":"D004342"}]},{"id":"6202","type":"Chemical","text":["amoxicillin"],"offsets":[[32,43]],"normalized":[{"db_name":"MESH","db_id":"D000658"}]},{"id":"6203","type":"Disease","text":["allergic 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{"id":"6399","document_id":"8638206","passages":[{"id":"6400","type":"title","text":["Persistent paralysis after prolonged use of atracurium in the absence of corticosteroids."],"offsets":[[0,89]]},{"id":"6401","type":"abstract","text":["Neuromuscular blocking agents (NMBAs) are often used for patients requiring prolonged mechanical ventilation. Reports of persistent paralysis after the discontinuance of these drugs have most often involved aminosteroid-based NMBAs such as vecuronium bromide, especially when used in conjunction with corticosteroids. Atracurium besylate, a short-acting benzylisoquinolinium NMBA that is eliminated independently of renal or hepatic function, has also been associated with persistent paralysis, but only when used with corticosteroids. We report a case of atracurium-related paralysis persisting for approximately 50 hours in a patient who was not treated with corticosteroids."],"offsets":[[90,767]]}],"entities":[{"id":"6402","type":"Disease","text":["paralysis"],"offsets":[[11,20]],"normalized":[{"db_name":"MESH","db_id":"D010243"}]},{"id":"6403","type":"Chemical","text":["atracurium"],"offsets":[[44,54]],"normalized":[{"db_name":"MESH","db_id":"D001279"}]},{"id":"6404","type":"Disease","text":["paralysis"],"offsets":[[222,231]],"normalized":[{"db_name":"MESH","db_id":"D010243"}]},{"id":"6405","type":"Chemical","text":["vecuronium bromide"],"offsets":[[330,348]],"normalized":[{"db_name":"MESH","db_id":"D014673"}]},{"id":"6406","type":"Chemical","text":["Atracurium besylate"],"offsets":[[408,427]],"normalized":[{"db_name":"MESH","db_id":"D001279"}]},{"id":"6407","type":"Chemical","text":["benzylisoquinolinium"],"offsets":[[444,464]],"normalized":[]},{"id":"6408","type":"Disease","text":["paralysis"],"offsets":[[574,583]],"normalized":[{"db_name":"MESH","db_id":"D010243"}]},{"id":"6409","type":"Chemical","text":["atracurium"],"offsets":[[646,656]],"normalized":[{"db_name":"MESH","db_id":"D001279"}]},{"id":"6410","type":"Disease","text":["paralysis"],"offsets":[[665,674]],"normalized":[{"db_name":"MESH","db_id":"D010243"}]}],"events":[],"coreferences":[],"relations":[{"id":"6411","type":"CID","arg1_id":"6403","arg2_id":"6402","normalized":[]},{"id":"6412","type":"CID","arg1_id":"6403","arg2_id":"6404","normalized":[]},{"id":"6413","type":"CID","arg1_id":"6403","arg2_id":"6408","normalized":[]},{"id":"6414","type":"CID","arg1_id":"6403","arg2_id":"6410","normalized":[]},{"id":"6415","type":"CID","arg1_id":"6406","arg2_id":"6402","normalized":[]},{"id":"6416","type":"CID","arg1_id":"6406","arg2_id":"6404","normalized":[]},{"id":"6417","type":"CID","arg1_id":"6406","arg2_id":"6408","normalized":[]},{"id":"6418","type":"CID","arg1_id":"6406","arg2_id":"6410","normalized":[]},{"id":"6419","type":"CID","arg1_id":"6409","arg2_id":"6402","normalized":[]},{"id":"6420","type":"CID","arg1_id":"6409","arg2_id":"6404","normalized":[]},{"id":"6421","type":"CID","arg1_id":"6409","arg2_id":"6408","normalized":[]},{"id":"6422","type":"CID","arg1_id":"6409","arg2_id":"6410","normalized":[]},{"id":"6423","type":"CID","arg1_id":"6405","arg2_id":"6402","normalized":[]},{"id":"6424","type":"CID","arg1_id":"6405","arg2_id":"6404","normalized":[]},{"id":"6425","type":"CID","arg1_id":"6405","arg2_id":"6408","normalized":[]},{"id":"6426","type":"CID","arg1_id":"6405","arg2_id":"6410","normalized":[]}]}
{"id":"6427","document_id":"8669433","passages":[{"id":"6428","type":"title","text":["Habitual use of acetaminophen as a risk factor for chronic renal failure: a comparison with phenacetin."],"offsets":[[0,103]]},{"id":"6429","type":"abstract","text":["Six epidemiologic studies in the United States and Europe indicate that habitual use of phenacetin is associated with the development of chronic renal failure and end-stage renal disease (ESRD), with a relative risk in the range of 4 to 19. As a result of these and other studies, phenacetin has now been withdrawn from the market in most countries. However, three case control studies, one each in North Carolina, northern Maryland, and West Berlin, Germany, showed that habitual use of acetaminophen is also associated with chronic renal failure and ESRD, with a relative risk in the range of 2 to 4. These studies suggest that both phenacetin and acetaminophen may contribute to the burden of ESRD, with the risk of the latter being somewhat less than that of the former. This apparent difference in risk may not be due to differences in nephrotoxic potential of the drugs themselves. A lower relative risk would be expected for acetaminophen if the risk of both drugs in combination with other analgesics was higher than the risk of either agent alone. Thus, acetaminophen has been used both as a single agent and in combination with other analgesics, whereas phenacetin was available only in combinations. The possibility that habitual use of acetaminophen alone increases the risk of ESRD has not been clearly demonstrated, but cannot be dismissed."],"offsets":[[104,1458]]}],"entities":[{"id":"6430","type":"Chemical","text":["acetaminophen"],"offsets":[[16,29]],"normalized":[{"db_name":"MESH","db_id":"D000082"}]},{"id":"6431","type":"Disease","text":["chronic renal failure"],"offsets":[[51,72]],"normalized":[{"db_name":"MESH","db_id":"D007676"}]},{"id":"6432","type":"Chemical","text":["phenacetin"],"offsets":[[92,102]],"normalized":[{"db_name":"MESH","db_id":"D010615"}]},{"id":"6433","type":"Chemical","text":["phenacetin"],"offsets":[[192,202]],"normalized":[{"db_name":"MESH","db_id":"D010615"}]},{"id":"6434","type":"Disease","text":["chronic renal failure"],"offsets":[[241,262]],"normalized":[{"db_name":"MESH","db_id":"D007676"}]},{"id":"6435","type":"Disease","text":["end-stage renal 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{"id":"6490","document_id":"8690168","passages":[{"id":"6491","type":"title","text":["Reduction of heparan sulphate-associated anionic sites in the glomerular basement membrane of rats with streptozotocin-induced diabetic nephropathy."],"offsets":[[0,148]]},{"id":"6492","type":"abstract","text":["Heparan sulphate-associated anionic sites in the glomerular basement membrane were studied in rats 8 months after induction of diabetes by streptozotocin and in age- adn sex-matched control rats, employing the cationic dye cuprolinic blue. Morphometric analysis at the ultrastructural level was performed using a computerized image processor. The heparan sulphate specificity of the cuprolinic blue staining was demonstrated by glycosaminoglycan-degrading enzymes, showing that pretreatment of the sections with heparitinase abolished all staining, whereas chondroitinase ABC had no effect. The majority of anionic sites (74% in diabetic and 81% in control rats) were found within the lamina rara externa of the glomerular basement membrane. A minority of anionic sites were scattered throughout the lamina densa and lamina rara interna, and were significantly smaller than those in the lamina rara externa of the glomerular basement membrane (p<0.001 and p<0.01 for diabetic and control rats, respectively). Diabetic rats progressively developed albuminuria reaching 40.3 (32.2-62.0) mg\/24 h after 8 months in contrast to the control animals (0.8 (0.2-0.9) mg\/24 h, p<0.002). At the same time, the number of heparan sulphate anionic sites and the total anionic site surface (number of anionic sites x mean anionic site surface) in the lamina rara externa of the glomerular basement membrane was reduced by 19% (p<0.021) and by 26% (p<0.02), respectively. Number and total anionic site surface in the remaining part of the glomerular basement membrane (lamina densa and lamina rara interna) were not significantly changed. We conclude that in streptozotocin-diabetic rats with an increased urinary albumin excretion, a reduced heparan sulphate charge barrier\/density is found at the lamina rara externa of the glomerular basement membrane."],"offsets":[[149,1988]]}],"entities":[{"id":"6493","type":"Chemical","text":["heparan sulphate"],"offsets":[[13,29]],"normalized":[{"db_name":"MESH","db_id":"D006497"}]},{"id":"6494","type":"Chemical","text":["streptozotocin"],"offsets":[[104,118]],"normalized":[{"db_name":"MESH","db_id":"D013311"}]},{"id":"6495","type":"Disease","text":["diabetic nephropathy"],"offsets":[[127,147]],"normalized":[{"db_name":"MESH","db_id":"D003928"}]},{"id":"6496","type":"Chemical","text":["Heparan sulphate"],"offsets":[[149,165]],"normalized":[{"db_name":"MESH","db_id":"D006497"}]},{"id":"6497","type":"Disease","text":["diabetes"],"offsets":[[276,284]],"normalized":[{"db_name":"MESH","db_id":"D003920"}]},{"id":"6498","type":"Chemical","text":["streptozotocin"],"offsets":[[288,302]],"normalized":[{"db_name":"MESH","db_id":"D013311"}]},{"id":"6499","type":"Chemical","text":["cuprolinic blue"],"offsets":[[372,387]],"normalized":[{"db_name":"MESH","db_id":"C015445"}]},{"id":"6500","type":"Chemical","text":["heparan sulphate"],"offsets":[[496,512]],"normalized":[{"db_name":"MESH","db_id":"D006497"}]},{"id":"6501","type":"Chemical","text":["cuprolinic blue"],"offsets":[[532,547]],"normalized":[{"db_name":"MESH","db_id":"C015445"}]},{"id":"6502","type":"Chemical","text":["glycosaminoglycan"],"offsets":[[577,594]],"normalized":[{"db_name":"MESH","db_id":"D006025"}]},{"id":"6503","type":"Disease","text":["diabetic"],"offsets":[[778,786]],"normalized":[{"db_name":"MESH","db_id":"D003920"}]},{"id":"6504","type":"Disease","text":["diabetic"],"offsets":[[1116,1124]],"normalized":[{"db_name":"MESH","db_id":"D003920"}]},{"id":"6505","type":"Disease","text":["Diabetic"],"offsets":[[1158,1166]],"normalized":[{"db_name":"MESH","db_id":"D003920"}]},{"id":"6506","type":"Disease","text":["albuminuria"],"offsets":[[1196,1207]],"normalized":[{"db_name":"MESH","db_id":"D000419"}]},{"id":"6507","type":"Chemical","text":["heparan sulphate"],"offsets":[[1358,1374]],"normalized":[{"db_name":"MESH","db_id":"D006497"}]},{"id":"6508","type":"Chemical","text":["streptozotocin"],"offsets":[[1792,1806]],"normalized":[{"db_name":"MESH","db_id":"D013311"}]},{"id":"6509","type":"Disease","text":["diabetic"],"offsets":[[1807,1815]],"normalized":[{"db_name":"MESH","db_id":"D003920"}]},{"id":"6510","type":"Chemical","text":["heparan sulphate"],"offsets":[[1876,1892]],"normalized":[{"db_name":"MESH","db_id":"D006497"}]}],"events":[],"coreferences":[],"relations":[{"id":"6511","type":"CID","arg1_id":"6494","arg2_id":"6495","normalized":[]},{"id":"6512","type":"CID","arg1_id":"6498","arg2_id":"6495","normalized":[]},{"id":"6513","type":"CID","arg1_id":"6508","arg2_id":"6495","normalized":[]}]}
{"id":"6514","document_id":"8739323","passages":[{"id":"6515","type":"title","text":["Effect of some anticancer drugs and combined chemotherapy on renal toxicity."],"offsets":[[0,76]]},{"id":"6516","type":"abstract","text":["The nephrotoxic action of anticancer drugs such as nitrogranulogen (NG), methotrexate (MTX), 5-fluorouracil (5-FU) and cyclophosphamide (CY) administered alone or in combination [MTX + 5-FU + CY (CMF)] was evaluated in experiments on Wistar rats. After drug administration, creatinine concentrations in the plasma and in the urine of the rats were determined, as well as creatinine clearance. Histopathologic evaluation of the kidneys was also performed. After MTX administration a significant increase (p = 0.0228) in the plasma creatinine concentration and a significant (p = 0.0001) decrease in creatinine clearance was noted compared to controls. After the administration of NG, 5-FU and CY neither a statistically significant increase in creatinine concentration nor an increase in creatinine clearance was observed compared to the group receiving no cytostatics. Following polytherapy according to the CMF regimen, a statistically significant decrease (p = 0.0343) in creatinine clearance was found, but creatinine concentration did not increase significantly compared to controls. CY caused hemorrhagic cystitis in 40% of rats, but it did not cause this complication when combined with 5-FU and MTX. Histologic changes were found in rat kidneys after administration of MTX, CY and NG, while no such change was observed after 5-FU and joint administration of MTX + 5-FU + CY compared to controls. Our studies indicate that nephrotoxicity of MTX + 5-FU + CY administered jointly is lower than in monotherapy."],"offsets":[[77,1590]]}],"entities":[{"id":"6517","type":"Disease","text":["renal toxicity"],"offsets":[[61,75]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"6518","type":"Disease","text":["nephrotoxic"],"offsets":[[81,92]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"6519","type":"Chemical","text":["nitrogranulogen"],"offsets":[[128,143]],"normalized":[{"db_name":"MESH","db_id":"D008466"}]},{"id":"6520","type":"Chemical","text":["NG"],"offsets":[[145,147]],"normalized":[{"db_name":"MESH","db_id":"D008466"}]},{"id":"6521","type":"Chemical","text":["methotrexate"],"offsets":[[150,162]],"normalized":[{"db_name":"MESH","db_id":"D008727"}]},{"id":"6522","type":"Chemical","text":["MTX"],"offsets":[[164,167]],"normalized":[{"db_name":"MESH","db_id":"D008727"}]},{"id":"6523","type":"Chemical","text":["5-fluorouracil"],"offsets":[[170,184]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"6524","type":"Chemical","text":["5-FU"],"offsets":[[186,190]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"6525","type":"Chemical","text":["cyclophosphamide"],"offsets":[[196,212]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"6526","type":"Chemical","text":["CY"],"offsets":[[214,216]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"6527","type":"Chemical","text":["MTX"],"offsets":[[256,259]],"normalized":[{"db_name":"MESH","db_id":"D008727"}]},{"id":"6528","type":"Chemical","text":["5-FU"],"offsets":[[262,266]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"6529","type":"Chemical","text":["CY"],"offsets":[[269,271]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"6530","type":"Chemical","text":["creatinine"],"offsets":[[351,361]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"6531","type":"Chemical","text":["creatinine"],"offsets":[[448,458]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"6532","type":"Chemical","text":["MTX"],"offsets":[[538,541]],"normalized":[{"db_name":"MESH","db_id":"D008727"}]},{"id":"6533","type":"Chemical","text":["creatinine"],"offsets":[[607,617]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"6534","type":"Chemical","text":["creatinine"],"offsets":[[675,685]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"6535","type":"Chemical","text":["NG"],"offsets":[[756,758]],"normalized":[{"db_name":"MESH","db_id":"D008466"}]},{"id":"6536","type":"Chemical","text":["5-FU"],"offsets":[[760,764]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"6537","type":"Chemical","text":["CY"],"offsets":[[769,771]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"6538","type":"Chemical","text":["creatinine"],"offsets":[[820,830]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"6539","type":"Chemical","text":["creatinine"],"offsets":[[864,874]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"6540","type":"Chemical","text":["creatinine"],"offsets":[[1051,1061]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"6541","type":"Chemical","text":["creatinine"],"offsets":[[1087,1097]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"6542","type":"Chemical","text":["CY"],"offsets":[[1165,1167]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"6543","type":"Disease","text":["hemorrhagic cystitis"],"offsets":[[1175,1195]],"normalized":[{"db_name":"MESH","db_id":"D006470"},{"db_name":"MESH","db_id":"D003556"}]},{"id":"6544","type":"Disease","text":["hemorrhagic"],"offsets":[[1175,1186]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"6545","type":"Disease","text":["cystitis"],"offsets":[[1187,1195]],"normalized":[{"db_name":"MESH","db_id":"D003556"}]},{"id":"6546","type":"Chemical","text":["5-FU"],"offsets":[[1270,1274]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"6547","type":"Chemical","text":["MTX"],"offsets":[[1279,1282]],"normalized":[{"db_name":"MESH","db_id":"D008727"}]},{"id":"6548","type":"Chemical","text":["MTX"],"offsets":[[1353,1356]],"normalized":[{"db_name":"MESH","db_id":"D008727"}]},{"id":"6549","type":"Chemical","text":["CY"],"offsets":[[1358,1360]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"6550","type":"Chemical","text":["NG"],"offsets":[[1365,1367]],"normalized":[{"db_name":"MESH","db_id":"D008466"}]},{"id":"6551","type":"Chemical","text":["5-FU"],"offsets":[[1409,1413]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"6552","type":"Chemical","text":["MTX"],"offsets":[[1442,1445]],"normalized":[{"db_name":"MESH","db_id":"D008727"}]},{"id":"6553","type":"Chemical","text":["5-FU"],"offsets":[[1448,1452]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"6554","type":"Chemical","text":["CY"],"offsets":[[1455,1457]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"6555","type":"Disease","text":["nephrotoxicity"],"offsets":[[1506,1520]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"6556","type":"Chemical","text":["MTX"],"offsets":[[1524,1527]],"normalized":[{"db_name":"MESH","db_id":"D008727"}]},{"id":"6557","type":"Chemical","text":["5-FU"],"offsets":[[1530,1534]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"6558","type":"Chemical","text":["CY"],"offsets":[[1537,1539]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]}],"events":[],"coreferences":[],"relations":[{"id":"6559","type":"CID","arg1_id":"6525","arg2_id":"6543","normalized":[]},{"id":"6560","type":"CID","arg1_id":"6525","arg2_id":"6544","normalized":[]},{"id":"6561","type":"CID","arg1_id":"6526","arg2_id":"6543","normalized":[]},{"id":"6562","type":"CID","arg1_id":"6526","arg2_id":"6544","normalized":[]},{"id":"6563","type":"CID","arg1_id":"6529","arg2_id":"6543","normalized":[]},{"id":"6564","type":"CID","arg1_id":"6529","arg2_id":"6544","normalized":[]},{"id":"6565","type":"CID","arg1_id":"6537","arg2_id":"6543","normalized":[]},{"id":"6566","type":"CID","arg1_id":"6537","arg2_id":"6544","normalized":[]},{"id":"6567","type":"CID","arg1_id":"6542","arg2_id":"6543","normalized":[]},{"id":"6568","type":"CID","arg1_id":"6542","arg2_id":"6544","normalized":[]},{"id":"6569","type":"CID","arg1_id":"6549","arg2_id":"6543","normalized":[]},{"id":"6570","type":"CID","arg1_id":"6549","arg2_id":"6544","normalized":[]},{"id":"6571","type":"CID","arg1_id":"6554","arg2_id":"6543","normalized":[]},{"id":"6572","type":"CID","arg1_id":"6554","arg2_id":"6544","normalized":[]},{"id":"6573","type":"CID","arg1_id":"6558","arg2_id":"6543","normalized":[]},{"id":"6574","type":"CID","arg1_id":"6558","arg2_id":"6544","normalized":[]},{"id":"6575","type":"CID","arg1_id":"6525","arg2_id":"6543","normalized":[]},{"id":"6576","type":"CID","arg1_id":"6525","arg2_id":"6545","normalized":[]},{"id":"6577","type":"CID","arg1_id":"6526","arg2_id":"6543","normalized":[]},{"id":"6578","type":"CID","arg1_id":"6526","arg2_id":"6545","normalized":[]},{"id":"6579","type":"CID","arg1_id":"6529","arg2_id":"6543","normalized":[]},{"id":"6580","type":"CID","arg1_id":"6529","arg2_id":"6545","normalized":[]},{"id":"6581","type":"CID","arg1_id":"6537","arg2_id":"6543","normalized":[]},{"id":"6582","type":"CID","arg1_id":"6537","arg2_id":"6545","normalized":[]},{"id":"6583","type":"CID","arg1_id":"6542","arg2_id":"6543","normalized":[]},{"id":"6584","type":"CID","arg1_id":"6542","arg2_id":"6545","normalized":[]},{"id":"6585","type":"CID","arg1_id":"6549","arg2_id":"6543","normalized":[]},{"id":"6586","type":"CID","arg1_id":"6549","arg2_id":"6545","normalized":[]},{"id":"6587","type":"CID","arg1_id":"6554","arg2_id":"6543","normalized":[]},{"id":"6588","type":"CID","arg1_id":"6554","arg2_id":"6545","normalized":[]},{"id":"6589","type":"CID","arg1_id":"6558","arg2_id":"6543","normalized":[]},{"id":"6590","type":"CID","arg1_id":"6558","arg2_id":"6545","normalized":[]}]}
{"id":"6591","document_id":"8752018","passages":[{"id":"6592","type":"title","text":["Lithium-associated cognitive and functional deficits reduced by a switch to divalproex sodium: a case series."],"offsets":[[0,109]]},{"id":"6593","type":"abstract","text":["BACKGROUND: Lithium remains a first-line treatment for the acute and maintenance treatment of bipolar disorder. Although much has been written about the management of the more common adverse effects of lithium, such as polyuria and tremor, more subtle lithium side effects such as cognitive deficits, loss of creativity, and functional impairments remain understudied. This report summarizes our experience in switching bipolar patients from lithium to divalproex sodium to alleviate such cognitive and functional impairments. METHOD: Open, case series design. RESULTS: We report seven cases where substitution of lithium, either fully or partially, with divalproex sodium was extremely helpful in reducing the cognitive, motivational, or creative deficits attributed to lithium in our bipolar patients. CONCLUSION: In this preliminary report, divalproex sodium was a superior alternative to lithium in bipolar patients experiencing cognitive deficits, loss of creativity, and functional impairments."],"offsets":[[110,1110]]}],"entities":[{"id":"6594","type":"Chemical","text":["Lithium"],"offsets":[[0,7]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"6595","type":"Disease","text":["cognitive and functional deficits"],"offsets":[[19,52]],"normalized":[{"db_name":"MESH","db_id":"D003072"}]},{"id":"6596","type":"Chemical","text":["divalproex sodium"],"offsets":[[76,93]],"normalized":[{"db_name":"MESH","db_id":"D014635"}]},{"id":"6597","type":"Chemical","text":["Lithium"],"offsets":[[122,129]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"6598","type":"Disease","text":["bipolar 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{"id":"6693","document_id":"9390208","passages":[{"id":"6694","type":"title","text":["Treatment of previously treated metastatic breast cancer by mitoxantrone and 48-hour continuous infusion of high-dose 5-FU and leucovorin (MFL): low palliative benefit and high treatment-related toxicity."],"offsets":[[0,204]]},{"id":"6695","type":"abstract","text":["For previously treated advanced breast cancer, there is no standard second-line therapy. Combination chemotherapy with mitoxantrone, high-dose 5-fluorouracil (5-FU) and leucovorin (MFL regimen) had been reported as an effective and well tolerated regimen. From October 1993 to November 1995, we treated 13 patients with previously chemotherapy-treated metastatic breast cancer by mitoxantrone, 12 mg\/m2, on day 1 and continuous infusion of 5-FU, 3000 mg\/m2, together with leucovorin, 300 mg\/m2, for 48 h from day 1 to 2. Each course of chemotherapy was given every 4 weeks. Most of these patients had more than two metastatic sites, with lung metastasis predominant. Seven patients had been treated with anthracycline. Seven patients had previously received radiotherapy and seven had received hormone therapy. Median number of courses of MFL regimen given was six and the median cumulative dose of mitoxantrone was 68.35 mg\/m2. One patient had complete response, seven had stable disease, none had partial response and five had progressive disease. The overall objective response rate was 7.6%. The median follow-up period was 14 months. Median survival was 16 months. Median progression-free survival was 5 months. A complete responder had relapse-free survival up to 17 months. Major toxicities were cardiotoxicity and leukopenia. Eight patients were dead in the last follow-up; two of them died of treatment-related toxicity. The MFL regimen achieves little palliative benefit and induces severe toxicity at a fairly high rate. Administration of this regimen to breast cancer patients who have been treated by chemotherapy and those with impaired heart function requires careful attention."],"offsets":[[205,1898]]}],"entities":[{"id":"6696","type":"Disease","text":["breast cancer"],"offsets":[[43,56]],"normalized":[{"db_name":"MESH","db_id":"D001943"}]},{"id":"6697","type":"Chemical","text":["mitoxantrone"],"offsets":[[60,72]],"normalized":[{"db_name":"MESH","db_id":"D008942"}]},{"id":"6698","type":"Chemical","text":["5-FU"],"offsets":[[118,122]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"6699","type":"Chemical","text":["leucovorin"],"offsets":[[127,137]],"normalized":[{"db_name":"MESH","db_id":"D002955"}]},{"id":"6700","type":"Chemical","text":["MFL"],"offsets":[[139,142]],"normalized":[{"db_name":"MESH","db_id":"C085788"}]},{"id":"6701","type":"Disease","text":["toxicity"],"offsets":[[195,203]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"6702","type":"Disease","text":["breast cancer"],"offsets":[[237,250]],"normalized":[{"db_name":"MESH","db_id":"D001943"}]},{"id":"6703","type":"Chemical","text":["mitoxantrone"],"offsets":[[324,336]],"normalized":[{"db_name":"MESH","db_id":"D008942"}]},{"id":"6704","type":"Chemical","text":["5-fluorouracil"],"offsets":[[348,362]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"6705","type":"Chemical","text":["5-FU"],"offsets":[[364,368]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"6706","type":"Chemical","text":["leucovorin"],"offsets":[[374,384]],"normalized":[{"db_name":"MESH","db_id":"D002955"}]},{"id":"6707","type":"Chemical","text":["MFL regimen"],"offsets":[[386,397]],"normalized":[{"db_name":"MESH","db_id":"C085788"}]},{"id":"6708","type":"Disease","text":["breast cancer"],"offsets":[[568,581]],"normalized":[{"db_name":"MESH","db_id":"D001943"}]},{"id":"6709","type":"Chemical","text":["mitoxantrone"],"offsets":[[585,597]],"normalized":[{"db_name":"MESH","db_id":"D008942"}]},{"id":"6710","type":"Chemical","text":["5-FU"],"offsets":[[645,649]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"6711","type":"Chemical","text":["leucovorin"],"offsets":[[677,687]],"normalized":[{"db_name":"MESH","db_id":"D002955"}]},{"id":"6712","type":"Chemical","text":["anthracycline"],"offsets":[[909,922]],"normalized":[{"db_name":"MESH","db_id":"D018943"}]},{"id":"6713","type":"Chemical","text":["MFL regimen"],"offsets":[[1044,1055]],"normalized":[{"db_name":"MESH","db_id":"C085788"}]},{"id":"6714","type":"Chemical","text":["mitoxantrone"],"offsets":[[1104,1116]],"normalized":[{"db_name":"MESH","db_id":"D008942"}]},{"id":"6715","type":"Disease","text":["toxicities"],"offsets":[[1492,1502]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"6716","type":"Disease","text":["cardiotoxicity"],"offsets":[[1508,1522]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"6717","type":"Disease","text":["leukopenia"],"offsets":[[1527,1537]],"normalized":[{"db_name":"MESH","db_id":"D007970"}]},{"id":"6718","type":"Disease","text":["toxicity"],"offsets":[[1625,1633]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"6719","type":"Chemical","text":["MFL regimen"],"offsets":[[1639,1650]],"normalized":[{"db_name":"MESH","db_id":"C085788"}]},{"id":"6720","type":"Disease","text":["toxicity"],"offsets":[[1705,1713]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"6721","type":"Disease","text":["breast cancer"],"offsets":[[1771,1784]],"normalized":[{"db_name":"MESH","db_id":"D001943"}]},{"id":"6722","type":"Disease","text":["impaired heart function"],"offsets":[[1847,1870]],"normalized":[{"db_name":"MESH","db_id":"D006331"}]}],"events":[],"coreferences":[],"relations":[{"id":"6723","type":"CID","arg1_id":"6700","arg2_id":"6722","normalized":[]},{"id":"6724","type":"CID","arg1_id":"6707","arg2_id":"6722","normalized":[]},{"id":"6725","type":"CID","arg1_id":"6713","arg2_id":"6722","normalized":[]},{"id":"6726","type":"CID","arg1_id":"6719","arg2_id":"6722","normalized":[]},{"id":"6727","type":"CID","arg1_id":"6700","arg2_id":"6717","normalized":[]},{"id":"6728","type":"CID","arg1_id":"6707","arg2_id":"6717","normalized":[]},{"id":"6729","type":"CID","arg1_id":"6713","arg2_id":"6717","normalized":[]},{"id":"6730","type":"CID","arg1_id":"6719","arg2_id":"6717","normalized":[]}]}
{"id":"6731","document_id":"9406968","passages":[{"id":"6732","type":"title","text":["Upregulation of the expression of vasopressin gene in the paraventricular and supraoptic nuclei of the lithium-induced diabetes insipidus rat."],"offsets":[[0,142]]},{"id":"6733","type":"abstract","text":["The expression of arginine vasopressin (AVP) gene in the paraventricular (PVN) and supraoptic nuclei (SON) was investigated in rats with lithium (Li)-induced polyuria, using in situ hybridization histochemistry and radioimmunoassay. The male Wistar rats consuming a diet that contained LiCl (60 mmol\/kg) for 4 weeks developed marked polyuria. The Li-treated rats produced a large volume of hypotonic urine with low ionic concentrations. Plasma sodium concentrations were found to be slightly increased in the Li-treated rats compared with those in controls. Plasma concentration of AVP and transcripts of AVP gene in the PVN and SON were significantly increased in the Li-treated rats compared with controls. These results suggest that dehydration and\/or the activation of visceral afferent inputs may contribute to the elevation of plasma AVP and the upregulation of AVP gene expression in the PVN and the SON of the Li-induced diabetes insipidus rat."],"offsets":[[143,1095]]}],"entities":[{"id":"6734","type":"Chemical","text":["vasopressin"],"offsets":[[34,45]],"normalized":[{"db_name":"MESH","db_id":"D014667"}]},{"id":"6735","type":"Chemical","text":["lithium"],"offsets":[[103,110]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"6736","type":"Disease","text":["diabetes insipidus"],"offsets":[[119,137]],"normalized":[{"db_name":"MESH","db_id":"D003919"}]},{"id":"6737","type":"Chemical","text":["arginine vasopressin"],"offsets":[[161,181]],"normalized":[{"db_name":"MESH","db_id":"D001127"}]},{"id":"6738","type":"Chemical","text":["AVP"],"offsets":[[183,186]],"normalized":[{"db_name":"MESH","db_id":"D001127"}]},{"id":"6739","type":"Chemical","text":["lithium"],"offsets":[[280,287]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"6740","type":"Chemical","text":["Li"],"offsets":[[289,291]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"6741","type":"Disease","text":["polyuria"],"offsets":[[301,309]],"normalized":[{"db_name":"MESH","db_id":"D011141"}]},{"id":"6742","type":"Chemical","text":["LiCl"],"offsets":[[429,433]],"normalized":[{"db_name":"MESH","db_id":"D018021"}]},{"id":"6743","type":"Disease","text":["polyuria"],"offsets":[[476,484]],"normalized":[{"db_name":"MESH","db_id":"D011141"}]},{"id":"6744","type":"Chemical","text":["Li"],"offsets":[[490,492]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"6745","type":"Chemical","text":["sodium"],"offsets":[[587,593]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"6746","type":"Chemical","text":["Li"],"offsets":[[652,654]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"6747","type":"Chemical","text":["AVP"],"offsets":[[725,728]],"normalized":[{"db_name":"MESH","db_id":"D001127"}]},{"id":"6748","type":"Chemical","text":["AVP"],"offsets":[[748,751]],"normalized":[{"db_name":"MESH","db_id":"D001127"}]},{"id":"6749","type":"Chemical","text":["Li"],"offsets":[[812,814]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"6750","type":"Disease","text":["dehydration"],"offsets":[[879,890]],"normalized":[{"db_name":"MESH","db_id":"D003681"}]},{"id":"6751","type":"Chemical","text":["AVP"],"offsets":[[983,986]],"normalized":[{"db_name":"MESH","db_id":"D001127"}]},{"id":"6752","type":"Chemical","text":["AVP"],"offsets":[[1011,1014]],"normalized":[{"db_name":"MESH","db_id":"D001127"}]},{"id":"6753","type":"Chemical","text":["Li"],"offsets":[[1061,1063]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"6754","type":"Disease","text":["diabetes insipidus"],"offsets":[[1072,1090]],"normalized":[{"db_name":"MESH","db_id":"D003919"}]}],"events":[],"coreferences":[],"relations":[{"id":"6755","type":"CID","arg1_id":"6742","arg2_id":"6741","normalized":[]},{"id":"6756","type":"CID","arg1_id":"6742","arg2_id":"6743","normalized":[]}]}
{"id":"6757","document_id":"9587734","passages":[{"id":"6758","type":"title","text":["Suxamethonium-induced cardiac arrest and death following 5 days of immobilization."],"offsets":[[0,82]]},{"id":"6759","type":"abstract","text":["The present report describes a case of cardiac arrest and subsequent death as a result of hyperkalaemia following the use of suxamethonium in a 23-year-old Malawian woman. Five days after the onset of the symptoms of meningitis, the patient aspirated stomach contents and needed endotracheal intubation. Forty seconds after injection of suxamethonium, bradycardia and cardiac arrest occurred. Attempts to resuscitate the patient were not successful. The serum level of potassium was observed to be 8.4 mequiv L-1. Apart from the reduction in the patient's level of consciousness, there were no signs of motor neurone damage or of any of the other known predisposing conditions for hyperkalaemia following the administration of suxamethonium. It is postulated that her death was caused by hypersensitivity to suxamethonium, associated with her 5-day immobilization."],"offsets":[[83,947]]}],"entities":[{"id":"6760","type":"Chemical","text":["Suxamethonium"],"offsets":[[0,13]],"normalized":[{"db_name":"MESH","db_id":"D013390"}]},{"id":"6761","type":"Disease","text":["cardiac arrest"],"offsets":[[22,36]],"normalized":[{"db_name":"MESH","db_id":"D006323"}]},{"id":"6762","type":"Disease","text":["death"],"offsets":[[41,46]],"normalized":[{"db_name":"MESH","db_id":"D003643"}]},{"id":"6763","type":"Disease","text":["cardiac 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arrest"],"offsets":[[451,465]],"normalized":[{"db_name":"MESH","db_id":"D006323"}]},{"id":"6771","type":"Chemical","text":["potassium"],"offsets":[[552,561]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"6772","type":"Disease","text":["hyperkalaemia"],"offsets":[[764,777]],"normalized":[{"db_name":"MESH","db_id":"D006947"}]},{"id":"6773","type":"Chemical","text":["suxamethonium"],"offsets":[[810,823]],"normalized":[{"db_name":"MESH","db_id":"D013390"}]},{"id":"6774","type":"Disease","text":["death"],"offsets":[[851,856]],"normalized":[{"db_name":"MESH","db_id":"D003643"}]},{"id":"6775","type":"Disease","text":["hypersensitivity"],"offsets":[[871,887]],"normalized":[{"db_name":"MESH","db_id":"D004342"}]},{"id":"6776","type":"Chemical","text":["suxamethonium"],"offsets":[[891,904]],"normalized":[{"db_name":"MESH","db_id":"D013390"}]}],"events":[],"coreferences":[],"relations":[{"id":"6777","type":"CID","arg1_id":"6760","arg2_id":"6775","normalized":[]},{"id":"6778","type":"CID","arg1_id":"6766","arg2_id":"6775","normalized":[]},{"id":"6779","type":"CID","arg1_id":"6768","arg2_id":"6775","normalized":[]},{"id":"6780","type":"CID","arg1_id":"6773","arg2_id":"6775","normalized":[]},{"id":"6781","type":"CID","arg1_id":"6776","arg2_id":"6775","normalized":[]},{"id":"6782","type":"CID","arg1_id":"6760","arg2_id":"6761","normalized":[]},{"id":"6783","type":"CID","arg1_id":"6760","arg2_id":"6763","normalized":[]},{"id":"6784","type":"CID","arg1_id":"6760","arg2_id":"6770","normalized":[]},{"id":"6785","type":"CID","arg1_id":"6766","arg2_id":"6761","normalized":[]},{"id":"6786","type":"CID","arg1_id":"6766","arg2_id":"6763","normalized":[]},{"id":"6787","type":"CID","arg1_id":"6766","arg2_id":"6770","normalized":[]},{"id":"6788","type":"CID","arg1_id":"6768","arg2_id":"6761","normalized":[]},{"id":"6789","type":"CID","arg1_id":"6768","arg2_id":"6763","normalized":[]},{"id":"6790","type":"CID","arg1_id":"6768","arg2_id":"6770","normalized":[]},{"id":"6791","type":"CID","arg1_id":"6773","arg2_id":"6761","normalized":[]},{"id":"6792","type":"CID","arg1_id":"6773","arg2_id":"6763","normalized":[]},{"id":"6793","type":"CID","arg1_id":"6773","arg2_id":"6770","normalized":[]},{"id":"6794","type":"CID","arg1_id":"6776","arg2_id":"6761","normalized":[]},{"id":"6795","type":"CID","arg1_id":"6776","arg2_id":"6763","normalized":[]},{"id":"6796","type":"CID","arg1_id":"6776","arg2_id":"6770","normalized":[]},{"id":"6797","type":"CID","arg1_id":"6760","arg2_id":"6765","normalized":[]},{"id":"6798","type":"CID","arg1_id":"6760","arg2_id":"6772","normalized":[]},{"id":"6799","type":"CID","arg1_id":"6766","arg2_id":"6765","normalized":[]},{"id":"6800","type":"CID","arg1_id":"6766","arg2_id":"6772","normalized":[]},{"id":"6801","type":"CID","arg1_id":"6768","arg2_id":"6765","normalized":[]},{"id":"6802","type":"CID","arg1_id":"6768","arg2_id":"6772","normalized":[]},{"id":"6803","type":"CID","arg1_id":"6773","arg2_id":"6765","normalized":[]},{"id":"6804","type":"CID","arg1_id":"6773","arg2_id":"6772","normalized":[]},{"id":"6805","type":"CID","arg1_id":"6776","arg2_id":"6765","normalized":[]},{"id":"6806","type":"CID","arg1_id":"6776","arg2_id":"6772","normalized":[]},{"id":"6807","type":"CID","arg1_id":"6760","arg2_id":"6769","normalized":[]},{"id":"6808","type":"CID","arg1_id":"6766","arg2_id":"6769","normalized":[]},{"id":"6809","type":"CID","arg1_id":"6768","arg2_id":"6769","normalized":[]},{"id":"6810","type":"CID","arg1_id":"6773","arg2_id":"6769","normalized":[]},{"id":"6811","type":"CID","arg1_id":"6776","arg2_id":"6769","normalized":[]}]}
{"id":"6812","document_id":"9698967","passages":[{"id":"6813","type":"title","text":["An unusual toxic reaction to axillary block by mepivacaine with adrenaline."],"offsets":[[0,75]]},{"id":"6814","type":"abstract","text":["An increase in blood pressure, accompanied by atrial fibrillation, agitation, incomprehensible shouts and loss of consciousness, was observed in an elderly, ASA classification group II, cardiovascularly medicated male, 12 min after performance of axillary block with mepivacaine 850 mg containing adrenaline 0.225 mg, for correction of Dupuytren's contracture. After intravenous administration of labetalol, metoprolol and midazolam the patient's condition improved, and 15 min later he woke up. The block was successful and surgery was conducted as scheduled despite persisting atrial fibrillation. Postoperatively, the patient refused DC cardioversion and was treated medically. Both the temporal relationship of events and the response to treatment suggest that a rapid systemic absorption of mepivacaine with adrenaline and\/or interaction of these drugs with the patient's cardiovascular medications were responsible for the perioperative complications."],"offsets":[[76,1033]]}],"entities":[{"id":"6815","type":"Chemical","text":["mepivacaine"],"offsets":[[47,58]],"normalized":[{"db_name":"MESH","db_id":"D008619"}]},{"id":"6816","type":"Chemical","text":["adrenaline"],"offsets":[[64,74]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"6817","type":"Disease","text":["increase in blood pressure"],"offsets":[[79,105]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"6818","type":"Disease","text":["atrial fibrillation"],"offsets":[[122,141]],"normalized":[{"db_name":"MESH","db_id":"D001281"}]},{"id":"6819","type":"Disease","text":["agitation"],"offsets":[[143,152]],"normalized":[{"db_name":"MESH","db_id":"D011595"}]},{"id":"6820","type":"Disease","text":["incomprehensible shouts"],"offsets":[[154,177]],"normalized":[{"db_name":"MESH","db_id":"D019954"}]},{"id":"6821","type":"Disease","text":["loss of consciousness"],"offsets":[[182,203]],"normalized":[{"db_name":"MESH","db_id":"D014474"}]},{"id":"6822","type":"Chemical","text":["mepivacaine"],"offsets":[[343,354]],"normalized":[{"db_name":"MESH","db_id":"D008619"}]},{"id":"6823","type":"Chemical","text":["adrenaline"],"offsets":[[373,383]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"6824","type":"Disease","text":["Dupuytren's contracture"],"offsets":[[412,435]],"normalized":[{"db_name":"MESH","db_id":"D004387"}]},{"id":"6825","type":"Chemical","text":["labetalol"],"offsets":[[473,482]],"normalized":[{"db_name":"MESH","db_id":"D007741"}]},{"id":"6826","type":"Chemical","text":["metoprolol"],"offsets":[[484,494]],"normalized":[{"db_name":"MESH","db_id":"D008790"}]},{"id":"6827","type":"Chemical","text":["midazolam"],"offsets":[[499,508]],"normalized":[{"db_name":"MESH","db_id":"D008874"}]},{"id":"6828","type":"Disease","text":["atrial fibrillation"],"offsets":[[655,674]],"normalized":[{"db_name":"MESH","db_id":"D001281"}]},{"id":"6829","type":"Chemical","text":["mepivacaine"],"offsets":[[872,883]],"normalized":[{"db_name":"MESH","db_id":"D008619"}]},{"id":"6830","type":"Chemical","text":["adrenaline"],"offsets":[[889,899]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]}],"events":[],"coreferences":[],"relations":[{"id":"6831","type":"CID","arg1_id":"6816","arg2_id":"6818","normalized":[]},{"id":"6832","type":"CID","arg1_id":"6816","arg2_id":"6828","normalized":[]},{"id":"6833","type":"CID","arg1_id":"6823","arg2_id":"6818","normalized":[]},{"id":"6834","type":"CID","arg1_id":"6823","arg2_id":"6828","normalized":[]},{"id":"6835","type":"CID","arg1_id":"6830","arg2_id":"6818","normalized":[]},{"id":"6836","type":"CID","arg1_id":"6830","arg2_id":"6828","normalized":[]},{"id":"6837","type":"CID","arg1_id":"6815","arg2_id":"6818","normalized":[]},{"id":"6838","type":"CID","arg1_id":"6815","arg2_id":"6828","normalized":[]},{"id":"6839","type":"CID","arg1_id":"6822","arg2_id":"6818","normalized":[]},{"id":"6840","type":"CID","arg1_id":"6822","arg2_id":"6828","normalized":[]},{"id":"6841","type":"CID","arg1_id":"6829","arg2_id":"6818","normalized":[]},{"id":"6842","type":"CID","arg1_id":"6829","arg2_id":"6828","normalized":[]},{"id":"6843","type":"CID","arg1_id":"6815","arg2_id":"6817","normalized":[]},{"id":"6844","type":"CID","arg1_id":"6822","arg2_id":"6817","normalized":[]},{"id":"6845","type":"CID","arg1_id":"6829","arg2_id":"6817","normalized":[]},{"id":"6846","type":"CID","arg1_id":"6816","arg2_id":"6817","normalized":[]},{"id":"6847","type":"CID","arg1_id":"6823","arg2_id":"6817","normalized":[]},{"id":"6848","type":"CID","arg1_id":"6830","arg2_id":"6817","normalized":[]}]}
{"id":"6849","document_id":"9855119","passages":[{"id":"6850","type":"title","text":["Clinical and histopathologic examination of renal allografts treated with tacrolimus (FK506) for at least one year."],"offsets":[[0,115]]},{"id":"6851","type":"abstract","text":["BACKGROUND: We clinically and pathologically analyzed renal allografts from 1 9 renal transplant patients treated with tacrolimus (FK506) for more than 1 year. METHODS: Twenty-six renal allograft biopsy specimens from 1 9 renal transplant patients who underwent transplantations between 1991 and 1993 were evaluated. Thirteen biopsies were performed from stable functioning renal allografts with informed consent (nonepisode biopsy) and the other 13 were from dysfunctional renal allografts with a clinical indication for biopsy (episode biopsy). RESULTS: The main pathologic diagnoses (some overlap) were acute rejection (AR; n = 4), chronic rejection (CR; n=5), AR+CR (n =4), recurrent IgA nephropathy (n =5), normal findings (n =2), minimal-type chronic FK506 nephropathy (n = 9), and mild-type FK506 nephropathy (n = 11). Of the nonepisode biopsies, 7 and 4 biopsies showed minimal-type and mild-type chronic FK506 nephropathy, respectively. Chronic FK506 nephropathy consisted of rough and foamy tubular vacuolization (5 biopsies), arteriolopathy (angiodegeneration of the arteriolar wall; 20 biopsies), focal segmental glomerulosclerosis (4 biopsies) and the striped form of interstitial fibrosis (11 biopsies). The serum creatinine levels of patients in the mild-type chronic FK506 nephropathy group, which included 7 episode biopsies, were statistically higher than those in the minimum-type chronic FK506-nephropathy group (P< 0.001). CONCLUSIONS: This study demonstrates that chronic FK506 nephropathy consists primarily of arteriolopathy manifesting as insudative hyalinosis of the arteriolar wall, and suggests that mild-type chronic FK506 nephropathy is a condition which may lead to deterioration of renal allograft function."],"offsets":[[116,1855]]}],"entities":[{"id":"6852","type":"Chemical","text":["tacrolimus"],"offsets":[[74,84]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"6853","type":"Chemical","text":["FK506"],"offsets":[[86,91]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"6854","type":"Chemical","text":["tacrolimus"],"offsets":[[235,245]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"6855","type":"Chemical","text":["FK506"],"offsets":[[247,252]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"6856","type":"Disease","text":["IgA nephropathy"],"offsets":[[804,819]],"normalized":[{"db_name":"MESH","db_id":"D005922"}]},{"id":"6857","type":"Chemical","text":["FK506"],"offsets":[[873,878]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"6858","type":"Disease","text":["nephropathy"],"offsets":[[879,890]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"6859","type":"Chemical","text":["FK506"],"offsets":[[914,919]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"6860","type":"Disease","text":["nephropathy"],"offsets":[[920,931]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"6861","type":"Chemical","text":["FK506"],"offsets":[[1029,1034]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"6862","type":"Disease","text":["nephropathy"],"offsets":[[1035,1046]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"6863","type":"Chemical","text":["FK506"],"offsets":[[1070,1075]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"6864","type":"Disease","text":["nephropathy"],"offsets":[[1076,1087]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"6865","type":"Disease","text":["focal segmental glomerulosclerosis"],"offsets":[[1225,1259]],"normalized":[{"db_name":"MESH","db_id":"D005923"}]},{"id":"6866","type":"Disease","text":["interstitial fibrosis"],"offsets":[[1297,1318]],"normalized":[{"db_name":"MESH","db_id":"D005355"}]},{"id":"6867","type":"Chemical","text":["creatinine"],"offsets":[[1344,1354]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"6868","type":"Chemical","text":["FK506"],"offsets":[[1399,1404]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"6869","type":"Disease","text":["nephropathy"],"offsets":[[1405,1416]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"6870","type":"Chemical","text":["FK506"],"offsets":[[1524,1529]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"6871","type":"Disease","text":["nephropathy"],"offsets":[[1530,1541]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"6872","type":"Chemical","text":["FK506"],"offsets":[[1610,1615]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"6873","type":"Disease","text":["nephropathy"],"offsets":[[1616,1627]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"6874","type":"Chemical","text":["FK506"],"offsets":[[1762,1767]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"6875","type":"Disease","text":["nephropathy"],"offsets":[[1768,1779]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]}],"events":[],"coreferences":[],"relations":[{"id":"6876","type":"CID","arg1_id":"6852","arg2_id":"6865","normalized":[]},{"id":"6877","type":"CID","arg1_id":"6853","arg2_id":"6865","normalized":[]},{"id":"6878","type":"CID","arg1_id":"6854","arg2_id":"6865","normalized":[]},{"id":"6879","type":"CID","arg1_id":"6855","arg2_id":"6865","normalized":[]},{"id":"6880","type":"CID","arg1_id":"6857","arg2_id":"6865","normalized":[]},{"id":"6881","type":"CID","arg1_id":"6859","arg2_id":"6865","normalized":[]},{"id":"6882","type":"CID","arg1_id":"6861","arg2_id":"6865","normalized":[]},{"id":"6883","type":"CID","arg1_id":"6863","arg2_id":"6865","normalized":[]},{"id":"6884","type":"CID","arg1_id":"6868","arg2_id":"6865","normalized":[]},{"id":"6885","type":"CID","arg1_id":"6870","arg2_id":"6865","normalized":[]},{"id":"6886","type":"CID","arg1_id":"6872","arg2_id":"6865","normalized":[]},{"id":"6887","type":"CID","arg1_id":"6874","arg2_id":"6865","normalized":[]}]}
{"id":"6888","document_id":"9869257","passages":[{"id":"6889","type":"title","text":["Memory facilitation and stimulation of endogenous nerve growth factor synthesis by the acetylcholine releaser PG-9."],"offsets":[[0,115]]},{"id":"6890","type":"abstract","text":["The effects of PG-9 (3alpha-tropyl 2-(p-bromophenyl)propionate), the acetylcholine releaser, on memory processes and nerve growth factor (NGF) synthesis were evaluated. In the mouse passive-avoidance test, PG-9 (10-30 mg\/kg, i.p.), administered 20 min before the training session, prevented amnesia induced by both the non selective antimuscarinic drug scopolamine and the M1-selective antagonist S-(-)-ET-126. In the same experimental conditions, PG-9 (5-20 microg per mouse, i.c.v.) was also able to prevent antimuscarine-induced amnesia, demonstrating a central localization of the activity. At the highest effective doses, PG-9 did not produce any collateral symptoms as revealed by the Irwin test, and it did not modify spontaneous motility and inspection activity, as revealed by the hole-board test. PG-9 was also able to increase the amount of NGF secreted in vitro by astrocytes in a dose-dependent manner. The maximal NGF contents obtained by PG-9 were 17.6-fold of the control value. During culture, no morphological changes were found at effective concentrations of PG-9. The current work indicates the ability of PG-9 to induce beneficial effects on cognitive processes and stimulate activity of NGF synthesis in astroglial cells. Therefore, PG-9 could represent a potential useful drug able to improve the function of impaired cognitive processes."],"offsets":[[116,1477]]}],"entities":[{"id":"6891","type":"Chemical","text":["acetylcholine"],"offsets":[[87,100]],"normalized":[{"db_name":"MESH","db_id":"D000109"}]},{"id":"6892","type":"Chemical","text":["PG-9"],"offsets":[[110,114]],"normalized":[{"db_name":"MESH","db_id":"C087567"}]},{"id":"6893","type":"Chemical","text":["PG-9"],"offsets":[[131,135]],"normalized":[{"db_name":"MESH","db_id":"C087567"}]},{"id":"6894","type":"Chemical","text":["3alpha-tropyl 2-(p-bromophenyl)propionate"],"offsets":[[137,178]],"normalized":[{"db_name":"MESH","db_id":"C087567"}]},{"id":"6895","type":"Chemical","text":["acetylcholine"],"offsets":[[185,198]],"normalized":[{"db_name":"MESH","db_id":"D000109"}]},{"id":"6896","type":"Chemical","text":["PG-9"],"offsets":[[322,326]],"normalized":[{"db_name":"MESH","db_id":"C087567"}]},{"id":"6897","type":"Disease","text":["amnesia"],"offsets":[[407,414]],"normalized":[{"db_name":"MESH","db_id":"D000647"}]},{"id":"6898","type":"Chemical","text":["scopolamine"],"offsets":[[469,480]],"normalized":[{"db_name":"MESH","db_id":"D012601"}]},{"id":"6899","type":"Chemical","text":["S-(-)-ET-126"],"offsets":[[513,525]],"normalized":[{"db_name":"MESH","db_id":"C098725"}]},{"id":"6900","type":"Chemical","text":["PG-9"],"offsets":[[564,568]],"normalized":[{"db_name":"MESH","db_id":"C087567"}]},{"id":"6901","type":"Disease","text":["amnesia"],"offsets":[[648,655]],"normalized":[{"db_name":"MESH","db_id":"D000647"}]},{"id":"6902","type":"Chemical","text":["PG-9"],"offsets":[[743,747]],"normalized":[{"db_name":"MESH","db_id":"C087567"}]},{"id":"6903","type":"Chemical","text":["PG-9"],"offsets":[[923,927]],"normalized":[{"db_name":"MESH","db_id":"C087567"}]},{"id":"6904","type":"Chemical","text":["PG-9"],"offsets":[[1069,1073]],"normalized":[{"db_name":"MESH","db_id":"C087567"}]},{"id":"6905","type":"Chemical","text":["PG-9"],"offsets":[[1194,1198]],"normalized":[{"db_name":"MESH","db_id":"C087567"}]},{"id":"6906","type":"Chemical","text":["PG-9"],"offsets":[[1242,1246]],"normalized":[{"db_name":"MESH","db_id":"C087567"}]},{"id":"6907","type":"Chemical","text":["PG-9"],"offsets":[[1371,1375]],"normalized":[{"db_name":"MESH","db_id":"C087567"}]}],"events":[],"coreferences":[],"relations":[{"id":"6908","type":"CID","arg1_id":"6899","arg2_id":"6897","normalized":[]},{"id":"6909","type":"CID","arg1_id":"6899","arg2_id":"6901","normalized":[]},{"id":"6910","type":"CID","arg1_id":"6898","arg2_id":"6897","normalized":[]},{"id":"6911","type":"CID","arg1_id":"6898","arg2_id":"6901","normalized":[]}]}
{"id":"6912","document_id":"10342929","passages":[{"id":"6913","type":"title","text":["Angioedema due to ACE inhibitors: common and inadequately diagnosed."],"offsets":[[0,68]]},{"id":"6914","type":"abstract","text":["The estimated incidence of angioedema during angiotensin-converting enzyme (ACE) inhibitor treatment is between 1 and 7 per thousand patients. This potentially serious adverse effect is often preceded by minor manifestations that may serve as a warning."],"offsets":[[69,322]]}],"entities":[{"id":"6915","type":"Disease","text":["Angioedema"],"offsets":[[0,10]],"normalized":[{"db_name":"MESH","db_id":"D000799"}]},{"id":"6916","type":"Chemical","text":["ACE inhibitors"],"offsets":[[18,32]],"normalized":[{"db_name":"MESH","db_id":"D000806"}]},{"id":"6917","type":"Disease","text":["angioedema"],"offsets":[[96,106]],"normalized":[{"db_name":"MESH","db_id":"D000799"}]},{"id":"6918","type":"Chemical","text":["angiotensin-converting enzyme (ACE) inhibitor"],"offsets":[[114,159]],"normalized":[{"db_name":"MESH","db_id":"D000806"}]}],"events":[],"coreferences":[],"relations":[{"id":"6919","type":"CID","arg1_id":"6916","arg2_id":"6915","normalized":[]},{"id":"6920","type":"CID","arg1_id":"6916","arg2_id":"6917","normalized":[]},{"id":"6921","type":"CID","arg1_id":"6918","arg2_id":"6915","normalized":[]},{"id":"6922","type":"CID","arg1_id":"6918","arg2_id":"6917","normalized":[]}]}
{"id":"6923","document_id":"10457883","passages":[{"id":"6924","type":"title","text":["Recurarization in the recovery room."],"offsets":[[0,36]]},{"id":"6925","type":"abstract","text":["A case of recurarization in the recovery room is reported. Accumulation of atracurium in the intravenous line led to recurarization after flushing the line in the recovery room. A respiratory arrest with severe desaturation and bradycardia occurred. Circumstances leading to this event and the mechanisms enabling a neuromuscular blockade to occur, following the administration of a small dose of relaxant, are discussed."],"offsets":[[37,458]]}],"entities":[{"id":"6926","type":"Chemical","text":["atracurium"],"offsets":[[112,122]],"normalized":[{"db_name":"MESH","db_id":"D001279"}]},{"id":"6927","type":"Disease","text":["respiratory arrest"],"offsets":[[217,235]],"normalized":[{"db_name":"MESH","db_id":"D012131"}]},{"id":"6928","type":"Disease","text":["desaturation"],"offsets":[[248,260]],"normalized":[{"db_name":"MESH","db_id":"D001049"}]},{"id":"6929","type":"Disease","text":["bradycardia"],"offsets":[[265,276]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"6930","type":"Disease","text":["neuromuscular blockade"],"offsets":[[353,375]],"normalized":[{"db_name":"MESH","db_id":"D020879"}]}],"events":[],"coreferences":[],"relations":[{"id":"6931","type":"CID","arg1_id":"6926","arg2_id":"6927","normalized":[]},{"id":"6932","type":"CID","arg1_id":"6926","arg2_id":"6929","normalized":[]},{"id":"6933","type":"CID","arg1_id":"6926","arg2_id":"6928","normalized":[]}]}
{"id":"6934","document_id":"10739826","passages":[{"id":"6935","type":"title","text":["Recurrent use of newer oral contraceptives and the risk of venous thromboembolism."],"offsets":[[0,82]]},{"id":"6936","type":"abstract","text":["The epidemiological studies that assessed the risk of venous thromboembolism (VTE) associated with newer oral contraceptives (OC) did not distinguish between patterns of OC use, namely first-time users, repeaters and switchers. Data from a Transnational case-control study were used to assess the risk of VTE for the latter patterns of use, while accounting for duration of use. Over the period 1993-1996, 551 cases of VTE were identified in Germany and the UK along with 2066 controls. Totals of 128 cases and 650 controls were analysed for repeat use and 135 cases and 622 controls for switching patterns. The adjusted rate ratio of VTE for repeat users of third generation OC was 0.6 (95% CI:0.3-1.2) relative to repeat users of second generation pills, whereas it was 1.3 (95% CI:0.7-2.4) for switchers from second to third generation pills relative to switchers from third to second generation pills. We conclude that second and third generation agents are associated with equivalent risks of VTE when the same agent is used repeatedly after interruption periods or when users are switched between the two generations of pills. These analyses suggest that the higher risk observed for the newer OC in other studies may be the result of inadequate comparisons of pill users with different patterns of pill use."],"offsets":[[83,1397]]}],"entities":[{"id":"6937","type":"Chemical","text":["oral contraceptives"],"offsets":[[23,42]],"normalized":[{"db_name":"MESH","db_id":"D003276"}]},{"id":"6938","type":"Disease","text":["venous thromboembolism"],"offsets":[[59,81]],"normalized":[{"db_name":"MESH","db_id":"D054556"}]},{"id":"6939","type":"Disease","text":["venous thromboembolism"],"offsets":[[137,159]],"normalized":[{"db_name":"MESH","db_id":"D054556"}]},{"id":"6940","type":"Disease","text":["VTE"],"offsets":[[161,164]],"normalized":[{"db_name":"MESH","db_id":"D054556"}]},{"id":"6941","type":"Chemical","text":["oral 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{"id":"6992","document_id":"10791295","passages":[{"id":"6993","type":"title","text":["Development of apomorphine-induced aggressive behavior: comparison of adult male and female Wistar rats."],"offsets":[[0,104]]},{"id":"6994","type":"abstract","text":["The development of apomorphine-induced (1.0 mg\/kg s.c. once daily) aggressive behavior of adult male and female Wistar rats obtained from the same breeder was studied in two consecutive sets. In male animals, repeated apomorphine treatment induced a gradual development of aggressive behavior as evidenced by the increased intensity of aggressiveness and shortened latency before the first attack toward the opponent. In female rats, only a weak tendency toward aggressiveness was found. In conclusion, the present study demonstrates gender differences in the development of the apomorphine-induced aggressive behavior and indicates that the female rats do not fill the validation criteria for use in this method."],"offsets":[[105,818]]}],"entities":[{"id":"6995","type":"Chemical","text":["apomorphine"],"offsets":[[15,26]],"normalized":[{"db_name":"MESH","db_id":"D001058"}]},{"id":"6996","type":"Disease","text":["aggressive behavior"],"offsets":[[35,54]],"normalized":[{"db_name":"MESH","db_id":"D010554"}]},{"id":"6997","type":"Chemical","text":["apomorphine"],"offsets":[[124,135]],"normalized":[{"db_name":"MESH","db_id":"D001058"}]},{"id":"6998","type":"Disease","text":["aggressive behavior"],"offsets":[[172,191]],"normalized":[{"db_name":"MESH","db_id":"D010554"}]},{"id":"6999","type":"Chemical","text":["apomorphine"],"offsets":[[323,334]],"normalized":[{"db_name":"MESH","db_id":"D001058"}]},{"id":"7000","type":"Disease","text":["aggressive behavior"],"offsets":[[378,397]],"normalized":[{"db_name":"MESH","db_id":"D010554"}]},{"id":"7001","type":"Disease","text":["aggressiveness"],"offsets":[[441,455]],"normalized":[{"db_name":"MESH","db_id":"D010554"}]},{"id":"7002","type":"Disease","text":["aggressiveness"],"offsets":[[567,581]],"normalized":[{"db_name":"MESH","db_id":"D010554"}]},{"id":"7003","type":"Chemical","text":["apomorphine"],"offsets":[[684,695]],"normalized":[{"db_name":"MESH","db_id":"D001058"}]},{"id":"7004","type":"Disease","text":["aggressive behavior"],"offsets":[[704,723]],"normalized":[{"db_name":"MESH","db_id":"D010554"}]}],"events":[],"coreferences":[],"relations":[{"id":"7005","type":"CID","arg1_id":"6995","arg2_id":"6996","normalized":[]},{"id":"7006","type":"CID","arg1_id":"6995","arg2_id":"6998","normalized":[]},{"id":"7007","type":"CID","arg1_id":"6995","arg2_id":"7000","normalized":[]},{"id":"7008","type":"CID","arg1_id":"6995","arg2_id":"7001","normalized":[]},{"id":"7009","type":"CID","arg1_id":"6995","arg2_id":"7002","normalized":[]},{"id":"7010","type":"CID","arg1_id":"6995","arg2_id":"7004","normalized":[]},{"id":"7011","type":"CID","arg1_id":"6997","arg2_id":"6996","normalized":[]},{"id":"7012","type":"CID","arg1_id":"6997","arg2_id":"6998","normalized":[]},{"id":"7013","type":"CID","arg1_id":"6997","arg2_id":"7000","normalized":[]},{"id":"7014","type":"CID","arg1_id":"6997","arg2_id":"7001","normalized":[]},{"id":"7015","type":"CID","arg1_id":"6997","arg2_id":"7002","normalized":[]},{"id":"7016","type":"CID","arg1_id":"6997","arg2_id":"7004","normalized":[]},{"id":"7017","type":"CID","arg1_id":"6999","arg2_id":"6996","normalized":[]},{"id":"7018","type":"CID","arg1_id":"6999","arg2_id":"6998","normalized":[]},{"id":"7019","type":"CID","arg1_id":"6999","arg2_id":"7000","normalized":[]},{"id":"7020","type":"CID","arg1_id":"6999","arg2_id":"7001","normalized":[]},{"id":"7021","type":"CID","arg1_id":"6999","arg2_id":"7002","normalized":[]},{"id":"7022","type":"CID","arg1_id":"6999","arg2_id":"7004","normalized":[]},{"id":"7023","type":"CID","arg1_id":"7003","arg2_id":"6996","normalized":[]},{"id":"7024","type":"CID","arg1_id":"7003","arg2_id":"6998","normalized":[]},{"id":"7025","type":"CID","arg1_id":"7003","arg2_id":"7000","normalized":[]},{"id":"7026","type":"CID","arg1_id":"7003","arg2_id":"7001","normalized":[]},{"id":"7027","type":"CID","arg1_id":"7003","arg2_id":"7002","normalized":[]},{"id":"7028","type":"CID","arg1_id":"7003","arg2_id":"7004","normalized":[]}]}
{"id":"7029","document_id":"11147747","passages":[{"id":"7030","type":"title","text":["Serotonergic antidepressants and urinary incontinence."],"offsets":[[0,54]]},{"id":"7031","type":"abstract","text":["Many new serotonergic antidepressants have been introduced over the past decade. Although urinary incontinence is listed as one side effect of these drugs in their package inserts there is only one report in the literature. This concerns 2 male patients who experienced incontinence while taking venlafaxine. In the present paper the authors describe 2 female patients who developed incontinence secondary to the selective serotonin reuptake inhibitors paroxetine and sertraline, as well as a third who developed this side effect on venlafaxine. In 2 of the 3 cases the patients were also taking lithium carbonate and beta-blockers, both of which could have contributed to the incontinence. Animal studies suggest that incontinence secondary to serotonergic antidepressants could be mediated by the 5HT4 receptors found on the bladder. Further research is needed to delineate the frequency of this troubling side effect and how best to treat it."],"offsets":[[55,1000]]}],"entities":[{"id":"7032","type":"Chemical","text":["Serotonergic antidepressants"],"offsets":[[0,28]],"normalized":[{"db_name":"MESH","db_id":"D018490"}]},{"id":"7033","type":"Disease","text":["urinary incontinence"],"offsets":[[33,53]],"normalized":[{"db_name":"MESH","db_id":"D014549"}]},{"id":"7034","type":"Chemical","text":["serotonergic antidepressants"],"offsets":[[64,92]],"normalized":[{"db_name":"MESH","db_id":"D018490"}]},{"id":"7035","type":"Disease","text":["urinary 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carbonate"],"offsets":[[651,668]],"normalized":[{"db_name":"MESH","db_id":"D016651"}]},{"id":"7044","type":"Disease","text":["incontinence"],"offsets":[[732,744]],"normalized":[{"db_name":"MESH","db_id":"D014549"}]},{"id":"7045","type":"Disease","text":["incontinence"],"offsets":[[774,786]],"normalized":[{"db_name":"MESH","db_id":"D014549"}]},{"id":"7046","type":"Chemical","text":["serotonergic 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{"id":"7095","document_id":"11198499","passages":[{"id":"7096","type":"title","text":["Hypotension following the initiation of tizanidine in a patient treated with an angiotensin converting enzyme inhibitor for chronic hypertension."],"offsets":[[0,145]]},{"id":"7097","type":"abstract","text":["Centrally acting alpha-2 adrenergic agonists are one of several pharmacologic agents used in the treatment of spasticity related to disorders of the central nervous system. In addition to their effects on spasticity, certain adverse cardiorespiratory effects have been reported. Adults chronically treated with angiotensin converting enzyme inhibitors may have a limited ability to respond to hypotension when the sympathetic response is simultaneously blocked. The authors present a 10-year-old boy chronically treated with lisinopril, an angiotensin converting enzyme inhibitor, to control hypertension who developed hypotension following the addition of tizanidine, an alpha-2 agonist, for the treatment of spasticity. The possible interaction of tizanidine and other antihypertensive agents should be kept in mind when prescribing therapy to treat either hypertension or spasticity in such patients."],"offsets":[[146,1049]]}],"entities":[{"id":"7098","type":"Disease","text":["Hypotension"],"offsets":[[0,11]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"7099","type":"Chemical","text":["tizanidine"],"offsets":[[40,50]],"normalized":[{"db_name":"MESH","db_id":"C023754"}]},{"id":"7100","type":"Chemical","text":["angiotensin"],"offsets":[[80,91]],"normalized":[{"db_name":"MESH","db_id":"D000809"}]},{"id":"7101","type":"Disease","text":["hypertension"],"offsets":[[132,144]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"7102","type":"Disease","text":["spasticity"],"offsets":[[256,266]],"normalized":[{"db_name":"MESH","db_id":"D009128"}]},{"id":"7103","type":"Disease","text":["disorders of the central nervous system"],"offsets":[[278,317]],"normalized":[{"db_name":"MESH","db_id":"D002493"}]},{"id":"7104","type":"Disease","text":["spasticity"],"offsets":[[351,361]],"normalized":[{"db_name":"MESH","db_id":"D009128"}]},{"id":"7105","type":"Chemical","text":["angiotensin"],"offsets":[[457,468]],"normalized":[{"db_name":"MESH","db_id":"D000809"}]},{"id":"7106","type":"Disease","text":["hypotension"],"offsets":[[539,550]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"7107","type":"Chemical","text":["lisinopril"],"offsets":[[671,681]],"normalized":[{"db_name":"MESH","db_id":"D017706"}]},{"id":"7108","type":"Chemical","text":["angiotensin"],"offsets":[[686,697]],"normalized":[{"db_name":"MESH","db_id":"D000809"}]},{"id":"7109","type":"Disease","text":["hypertension"],"offsets":[[738,750]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"7110","type":"Disease","text":["hypotension"],"offsets":[[765,776]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"7111","type":"Chemical","text":["tizanidine"],"offsets":[[803,813]],"normalized":[{"db_name":"MESH","db_id":"C023754"}]},{"id":"7112","type":"Disease","text":["spasticity"],"offsets":[[856,866]],"normalized":[{"db_name":"MESH","db_id":"D009128"}]},{"id":"7113","type":"Chemical","text":["tizanidine"],"offsets":[[896,906]],"normalized":[{"db_name":"MESH","db_id":"C023754"}]},{"id":"7114","type":"Disease","text":["hypertension"],"offsets":[[1005,1017]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"7115","type":"Disease","text":["spasticity"],"offsets":[[1021,1031]],"normalized":[{"db_name":"MESH","db_id":"D009128"}]}],"events":[],"coreferences":[],"relations":[{"id":"7116","type":"CID","arg1_id":"7099","arg2_id":"7098","normalized":[]},{"id":"7117","type":"CID","arg1_id":"7099","arg2_id":"7106","normalized":[]},{"id":"7118","type":"CID","arg1_id":"7099","arg2_id":"7110","normalized":[]},{"id":"7119","type":"CID","arg1_id":"7111","arg2_id":"7098","normalized":[]},{"id":"7120","type":"CID","arg1_id":"7111","arg2_id":"7106","normalized":[]},{"id":"7121","type":"CID","arg1_id":"7111","arg2_id":"7110","normalized":[]},{"id":"7122","type":"CID","arg1_id":"7113","arg2_id":"7098","normalized":[]},{"id":"7123","type":"CID","arg1_id":"7113","arg2_id":"7106","normalized":[]},{"id":"7124","type":"CID","arg1_id":"7113","arg2_id":"7110","normalized":[]},{"id":"7125","type":"CID","arg1_id":"7107","arg2_id":"7098","normalized":[]},{"id":"7126","type":"CID","arg1_id":"7107","arg2_id":"7106","normalized":[]},{"id":"7127","type":"CID","arg1_id":"7107","arg2_id":"7110","normalized":[]}]}
{"id":"7128","document_id":"11391224","passages":[{"id":"7129","type":"title","text":["Peritubular capillary basement membrane reduplication in allografts and native kidney disease: a clinicopathologic study of 278 consecutive renal specimens."],"offsets":[[0,156]]},{"id":"7130","type":"abstract","text":["BACKGROUND: An association has been found between transplant glomerulopathy (TG) and reduplication of peritubular capillary basement membranes (PTCR). Although such an association is of practical and theoretical importance, only one prospective study has tried to confirm it. METHODS: We examined 278 consecutive renal specimens (from 135 transplants and 143 native kidneys) for ultrastructural evidence of PTCR. In addition to renal allografts with TG, we also examined grafts with acute rejection, recurrent glomerulonephritis, chronic allograft nephropathy and stable grafts (\"protocol biopsies\"). Native kidney specimens included a wide range of glomerulopathies as well as cases of thrombotic microangiopathy, malignant hypertension, acute interstitial nephritis, and acute tubular necrosis. RESULTS: We found PTCR in 14 of 15 cases of TG, in 7 transplant biopsy specimens without TG, and in 13 of 143 native kidney biopsy specimens. These 13 included cases of malignant hypertension, thrombotic microangiopathy, lupus nephritis, Henoch-Schonlein nephritis, crescentic glomerulonephritis, and cocaine-related acute renal failure. Mild PTCR in allografts without TG did not predict renal failure or significant proteinuria after follow-up periods of between 3 months and 1 year. CONCLUSIONS: We conclude that in transplants, there is a strong association between well-developed PTCR and TG, while the significance of mild PTCR and its predictive value in the absence of TG is unclear. PTCR also occurs in certain native kidney diseases, though the association is not as strong as that for TG. We suggest that repeated endothelial injury, including immunologic injury, may be the cause of this lesion both in allografts and native kidneys."],"offsets":[[157,1899]]}],"entities":[{"id":"7131","type":"Disease","text":["kidney disease"],"offsets":[[79,93]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"7132","type":"Disease","text":["transplant glomerulopathy"],"offsets":[[207,232]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"7133","type":"Disease","text":["TG"],"offsets":[[234,236]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"7134","type":"Disease","text":["TG"],"offsets":[[607,609]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"7135","type":"Disease","text":["glomerulonephritis"],"offsets":[[667,685]],"normalized":[{"db_name":"MESH","db_id":"D005921"}]},{"id":"7136","type":"Disease","text":["chronic allograft nephropathy"],"offsets":[[687,716]],"normalized":[{"db_name":"MESH","db_id":"D051436"}]},{"id":"7137","type":"Disease","text":["glomerulopathies"],"offsets":[[807,823]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"7138","type":"Disease","text":["thrombotic microangiopathy"],"offsets":[[844,870]],"normalized":[{"db_name":"MESH","db_id":"D057049"}]},{"id":"7139","type":"Disease","text":["malignant hypertension"],"offsets":[[872,894]],"normalized":[{"db_name":"MESH","db_id":"D006974"}]},{"id":"7140","type":"Disease","text":["interstitial nephritis"],"offsets":[[902,924]],"normalized":[{"db_name":"MESH","db_id":"D009395"}]},{"id":"7141","type":"Disease","text":["acute tubular necrosis"],"offsets":[[930,952]],"normalized":[{"db_name":"MESH","db_id":"D007683"}]},{"id":"7142","type":"Disease","text":["TG"],"offsets":[[998,1000]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"7143","type":"Disease","text":["TG"],"offsets":[[1043,1045]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"7144","type":"Disease","text":["malignant hypertension"],"offsets":[[1123,1145]],"normalized":[{"db_name":"MESH","db_id":"D006974"}]},{"id":"7145","type":"Disease","text":["thrombotic microangiopathy"],"offsets":[[1147,1173]],"normalized":[{"db_name":"MESH","db_id":"D057049"}]},{"id":"7146","type":"Disease","text":["lupus nephritis"],"offsets":[[1175,1190]],"normalized":[{"db_name":"MESH","db_id":"D008181"}]},{"id":"7147","type":"Disease","text":["Henoch-Schonlein nephritis"],"offsets":[[1192,1218]],"normalized":[{"db_name":"MESH","db_id":"D011695"}]},{"id":"7148","type":"Disease","text":["glomerulonephritis"],"offsets":[[1231,1249]],"normalized":[{"db_name":"MESH","db_id":"D005921"}]},{"id":"7149","type":"Chemical","text":["cocaine"],"offsets":[[1255,1262]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"7150","type":"Disease","text":["acute renal failure"],"offsets":[[1271,1290]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"7151","type":"Disease","text":["TG"],"offsets":[[1324,1326]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"7152","type":"Disease","text":["renal failure"],"offsets":[[1343,1356]],"normalized":[{"db_name":"MESH","db_id":"D051437"}]},{"id":"7153","type":"Disease","text":["proteinuria"],"offsets":[[1372,1383]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]},{"id":"7154","type":"Disease","text":["TG"],"offsets":[[1548,1550]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"7155","type":"Disease","text":["TG"],"offsets":[[1631,1633]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"7156","type":"Disease","text":["kidney diseases"],"offsets":[[1681,1696]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"7157","type":"Disease","text":["TG"],"offsets":[[1750,1752]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"7158","type":"Disease","text":["endothelial injury"],"offsets":[[1779,1797]],"normalized":[{"db_name":"MESH","db_id":"D014947"}]},{"id":"7159","type":"Disease","text":["immunologic injury"],"offsets":[[1809,1827]],"normalized":[{"db_name":"MESH","db_id":"D007154"}]}],"events":[],"coreferences":[],"relations":[{"id":"7160","type":"CID","arg1_id":"7149","arg2_id":"7150","normalized":[]}]}
{"id":"7161","document_id":"11426838","passages":[{"id":"7162","type":"title","text":["Conformationally restricted analogs of BD1008 and an antisense oligodeoxynucleotide targeting sigma1 receptors produce anti-cocaine effects in mice."],"offsets":[[0,148]]},{"id":"7163","type":"abstract","text":["Cocaine's ability to interact with sigma receptors suggests that these proteins mediate some of its behavioral effects. Therefore, three novel sigma receptor ligands with antagonist activity were evaluated in Swiss Webster mice: BD1018 (3S-1-[2-(3,4-dichlorophenyl)ethyl]-1,4-diazabicyclo[4.3.0]nonane), BD1063 (1-[2-(3,4-dichlorophenyl)ethyl]-4-methylpiperazine), and LR132 (1R,2S-(+)-cis-N-[2-(3,4-dichlorophenyl)ethyl]-2-(1-pyrrolidinyl)cyclohexylamine). Competition binding assays demonstrated that all three compounds have high affinities for sigma1 receptors. The three compounds vary in their affinities for sigma2 receptors and exhibit negligible affinities for dopamine, opioid, GABA(A) and NMDA receptors. In behavioral studies, pre-treatment of mice with BD1018, BD1063, or LR132 significantly attenuated cocaine-induced convulsions and lethality. Moreover, post-treatment with LR132 prevented cocaine-induced lethality in a significant proportion of animals. In contrast to the protection provided by the putative antagonists, the well-characterized sigma receptor agonist di-o-tolylguanidine (DTG) and the novel sigma receptor agonist BD1031 (3R-1-[2-(3,4-dichlorophenyl)ethyl]-1,4-diazabicyclo[4.3.0]nonane) each worsened the behavioral toxicity of cocaine. At doses where alone, they produced no significant effects on locomotion, BD1018, BD1063 and LR132 significantly attenuated the locomotor stimulatory effects of cocaine. To further validate the hypothesis that the anti-cocaine effects of the novel ligands involved antagonism of sigma receptors, an antisense oligodeoxynucleotide against sigma1 receptors was also shown to significantly attenuate the convulsive and locomotor stimulatory effects of cocaine. Together, the data suggests that functional antagonism of sigma receptors is capable of attenuating a number of cocaine-induced behaviors."],"offsets":[[149,2017]]}],"entities":[{"id":"7164","type":"Chemical","text":["BD1008"],"offsets":[[39,45]],"normalized":[{"db_name":"MESH","db_id":"C085527"}]},{"id":"7165","type":"Chemical","text":["oligodeoxynucleotide"],"offsets":[[63,83]],"normalized":[{"db_name":"MESH","db_id":"D009838"}]},{"id":"7166","type":"Chemical","text":["cocaine"],"offsets":[[124,131]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"7167","type":"Chemical","text":["Cocaine"],"offsets":[[149,156]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"7168","type":"Chemical","text":["BD1018"],"offsets":[[378,384]],"normalized":[]},{"id":"7169","type":"Chemical","text":["3S-1-[2-(3,4-dichlorophenyl)ethyl]-1,4-diazabicyclo[4.3.0]nonane"],"offsets":[[386,450]],"normalized":[]},{"id":"7170","type":"Chemical","text":["BD1063"],"offsets":[[453,459]],"normalized":[{"db_name":"MESH","db_id":"C093337"}]},{"id":"7171","type":"Chemical","text":["1-[2-(3,4-dichlorophenyl)ethyl]-4-methylpiperazine"],"offsets":[[461,511]],"normalized":[{"db_name":"MESH","db_id":"C093337"}]},{"id":"7172","type":"Chemical","text":["LR132"],"offsets":[[518,523]],"normalized":[]},{"id":"7173","type":"Chemical","text":["dopamine"],"offsets":[[819,827]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"7174","type":"Chemical","text":["GABA"],"offsets":[[837,841]],"normalized":[{"db_name":"MESH","db_id":"D005680"}]},{"id":"7175","type":"Chemical","text":["NMDA"],"offsets":[[849,853]],"normalized":[{"db_name":"MESH","db_id":"D016202"}]},{"id":"7176","type":"Chemical","text":["BD1018"],"offsets":[[915,921]],"normalized":[]},{"id":"7177","type":"Chemical","text":["BD1063"],"offsets":[[923,929]],"normalized":[{"db_name":"MESH","db_id":"C093337"}]},{"id":"7178","type":"Chemical","text":["LR132"],"offsets":[[934,939]],"normalized":[]},{"id":"7179","type":"Chemical","text":["cocaine"],"offsets":[[965,972]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"7180","type":"Disease","text":["convulsions"],"offsets":[[981,992]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"7181","type":"Chemical","text":["LR132"],"offsets":[[1038,1043]],"normalized":[]},{"id":"7182","type":"Chemical","text":["cocaine"],"offsets":[[1054,1061]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"7183","type":"Chemical","text":["di-o-tolylguanidine"],"offsets":[[1234,1253]],"normalized":[{"db_name":"MESH","db_id":"C050232"}]},{"id":"7184","type":"Chemical","text":["DTG"],"offsets":[[1255,1258]],"normalized":[{"db_name":"MESH","db_id":"C050232"}]},{"id":"7185","type":"Chemical","text":["BD1031"],"offsets":[[1297,1303]],"normalized":[]},{"id":"7186","type":"Chemical","text":["3R-1-[2-(3,4-dichlorophenyl)ethyl]-1,4-diazabicyclo[4.3.0]nonane"],"offsets":[[1305,1369]],"normalized":[]},{"id":"7187","type":"Disease","text":["toxicity"],"offsets":[[1400,1408]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"7188","type":"Chemical","text":["cocaine"],"offsets":[[1412,1419]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"7189","type":"Chemical","text":["BD1018"],"offsets":[[1495,1501]],"normalized":[]},{"id":"7190","type":"Chemical","text":["BD1063"],"offsets":[[1503,1509]],"normalized":[{"db_name":"MESH","db_id":"C093337"}]},{"id":"7191","type":"Chemical","text":["LR132"],"offsets":[[1514,1519]],"normalized":[]},{"id":"7192","type":"Chemical","text":["cocaine"],"offsets":[[1582,1589]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"7193","type":"Chemical","text":["cocaine"],"offsets":[[1640,1647]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"7194","type":"Chemical","text":["oligodeoxynucleotide"],"offsets":[[1730,1750]],"normalized":[{"db_name":"MESH","db_id":"D009838"}]},{"id":"7195","type":"Disease","text":["convulsive"],"offsets":[[1822,1832]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"7196","type":"Chemical","text":["cocaine"],"offsets":[[1870,1877]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"7197","type":"Chemical","text":["cocaine"],"offsets":[[1991,1998]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]}],"events":[],"coreferences":[],"relations":[{"id":"7198","type":"CID","arg1_id":"7166","arg2_id":"7180","normalized":[]},{"id":"7199","type":"CID","arg1_id":"7166","arg2_id":"7195","normalized":[]},{"id":"7200","type":"CID","arg1_id":"7167","arg2_id":"7180","normalized":[]},{"id":"7201","type":"CID","arg1_id":"7167","arg2_id":"7195","normalized":[]},{"id":"7202","type":"CID","arg1_id":"7179","arg2_id":"7180","normalized":[]},{"id":"7203","type":"CID","arg1_id":"7179","arg2_id":"7195","normalized":[]},{"id":"7204","type":"CID","arg1_id":"7182","arg2_id":"7180","normalized":[]},{"id":"7205","type":"CID","arg1_id":"7182","arg2_id":"7195","normalized":[]},{"id":"7206","type":"CID","arg1_id":"7188","arg2_id":"7180","normalized":[]},{"id":"7207","type":"CID","arg1_id":"7188","arg2_id":"7195","normalized":[]},{"id":"7208","type":"CID","arg1_id":"7192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{"id":"7216","document_id":"11569530","passages":[{"id":"7217","type":"title","text":["Pharmacokinetic\/pharmacodynamic assessment of the effects of E4031, cisapride, terfenadine and terodiline on monophasic action potential duration in dog."],"offsets":[[0,153]]},{"id":"7218","type":"abstract","text":["1. Torsades de pointes (TDP) is a potentially fatal ventricular tachycardia associated with increases in QT interval and monophasic action potential duration (MAPD). TDP is a side-effect that has led to withdrawal of several drugs from the market (e.g. terfenadine and terodiline). 2. The potential of compounds to cause TDP was evaluated by monitoring their effects on MAPD in dog. Four compounds known to increase QT interval and cause TDP were investigated: terfenadine, terodiline, cisapride and E4031. On the basis that only free drug in the systemic circulation will elicit a pharmacological response target, free concentrations in plasma were selected to mimic the free drug exposures in man. Infusion regimens were designed that rapidly achieved and maintained target-free concentrations of these drugs in plasma and data on the relationship between free concentration and changes in MAPD were obtained for these compounds. 3. These data indicate that the free ED50 in plasma for terfenadine (1.9 nM), terodiline (76 nM), cisapride (11 nM) and E4031 (1.9 nM) closely correlate with the free concentration in man causing QT effects. For compounds that have shown TDP in the clinic (terfenadine, terodiline, cisapride) there is little differentiation between the dog ED50 and the efficacious free plasma concentrations in man (< 10-fold) reflecting their limited safety margins. These data underline the need to maximize the therapeutic ratio with respect to TDP in potential development candidates and the importance of using free drug concentrations in pharmacokinetic\/pharmacodynamic studies."],"offsets":[[154,1755]]}],"entities":[{"id":"7219","type":"Chemical","text":["E4031"],"offsets":[[61,66]],"normalized":[{"db_name":"MESH","db_id":"C063968"}]},{"id":"7220","type":"Chemical","text":["cisapride"],"offsets":[[68,77]],"normalized":[{"db_name":"MESH","db_id":"D020117"}]},{"id":"7221","type":"Chemical","text":["terfenadine"],"offsets":[[79,90]],"normalized":[{"db_name":"MESH","db_id":"D016593"}]},{"id":"7222","type":"Chemical","text":["terodiline"],"offsets":[[95,105]],"normalized":[{"db_name":"MESH","db_id":"C010637"}]},{"id":"7223","type":"Disease","text":["Torsades de pointes"],"offsets":[[157,176]],"normalized":[{"db_name":"MESH","db_id":"D016171"}]},{"id":"7224","type":"Disease","text":["TDP"],"offsets":[[178,181]],"normalized":[{"db_name":"MESH","db_id":"D016171"}]},{"id":"7225","type":"Disease","text":["ventricular tachycardia"],"offsets":[[206,229]],"normalized":[{"db_name":"MESH","db_id":"D017180"}]},{"id":"7226","type":"Disease","text":["TDP"],"offsets":[[320,323]],"normalized":[{"db_name":"MESH","db_id":"D016171"}]},{"id":"7227","type":"Chemical","text":["terfenadine"],"offsets":[[407,418]],"normalized":[{"db_name":"MESH","db_id":"D016593"}]},{"id":"7228","type":"Chemical","text":["terodiline"],"offsets":[[423,433]],"normalized":[{"db_name":"MESH","db_id":"C010637"}]},{"id":"7229","type":"Disease","text":["TDP"],"offsets":[[475,478]],"normalized":[{"db_name":"MESH","db_id":"D016171"}]},{"id":"7230","type":"Disease","text":["TDP"],"offsets":[[592,595]],"normalized":[{"db_name":"MESH","db_id":"D016171"}]},{"id":"7231","type":"Chemical","text":["terfenadine"],"offsets":[[615,626]],"normalized":[{"db_name":"MESH","db_id":"D016593"}]},{"id":"7232","type":"Chemical","text":["terodiline"],"offsets":[[628,638]],"normalized":[{"db_name":"MESH","db_id":"C010637"}]},{"id":"7233","type":"Chemical","text":["cisapride"],"offsets":[[640,649]],"normalized":[{"db_name":"MESH","db_id":"D020117"}]},{"id":"7234","type":"Chemical","text":["E4031"],"offsets":[[654,659]],"normalized":[{"db_name":"MESH","db_id":"C063968"}]},{"id":"7235","type":"Chemical","text":["terfenadine"],"offsets":[[1142,1153]],"normalized":[{"db_name":"MESH","db_id":"D016593"}]},{"id":"7236","type":"Chemical","text":["terodiline"],"offsets":[[1164,1174]],"normalized":[{"db_name":"MESH","db_id":"C010637"}]},{"id":"7237","type":"Chemical","text":["cisapride"],"offsets":[[1184,1193]],"normalized":[{"db_name":"MESH","db_id":"D020117"}]},{"id":"7238","type":"Chemical","text":["E4031"],"offsets":[[1206,1211]],"normalized":[{"db_name":"MESH","db_id":"C063968"}]},{"id":"7239","type":"Disease","text":["TDP"],"offsets":[[1324,1327]],"normalized":[{"db_name":"MESH","db_id":"D016171"}]},{"id":"7240","type":"Chemical","text":["terfenadine"],"offsets":[[1343,1354]],"normalized":[{"db_name":"MESH","db_id":"D016593"}]},{"id":"7241","type":"Chemical","text":["terodiline"],"offsets":[[1356,1366]],"normalized":[{"db_name":"MESH","db_id":"C010637"}]},{"id":"7242","type":"Chemical","text":["cisapride"],"offsets":[[1368,1377]],"normalized":[{"db_name":"MESH","db_id":"D020117"}]},{"id":"7243","type":"Disease","text":["TDP"],"offsets":[[1619,1622]],"normalized":[{"db_name":"MESH","db_id":"D016171"}]}],"events":[],"coreferences":[],"relations":[{"id":"7244","type":"CID","arg1_id":"7221","arg2_id":"7223","normalized":[]},{"id":"7245","type":"CID","arg1_id":"7221","arg2_id":"7224","normalized":[]},{"id":"7246","type":"CID","arg1_id":"7221","arg2_id":"7226","normalized":[]},{"id":"7247","type":"CID","arg1_id":"7221","arg2_id":"7229","normalized":[]},{"id":"7248","type":"CID","arg1_id":"7221","arg2_id":"7230","normalized":[]},{"id":"7249","type":"CID","arg1_id":"7221","arg2_id":"7239","normalized":[]},{"id":"7250","type":"CID","arg1_id":"7221","arg2_id":"7243","normalized":[]},{"id":"7251","type":"CID","arg1_id":"7227","arg2_id":"7223","normalized":[]},{"id":"7252","type":"CID","arg1_id":"7227","arg2_id":"7224","normalized":[]},{"id":"7253","type":"CID","arg1_id":"7227","arg2_id":"7226","normalized":[]},{"id":"7254","type":"CID","arg1_id":"7227","arg2_id":"7229","normalized":[]},{"id":"7255","type":"CID","arg1_id":"7227","arg2_id":"7230","normalized":[]},{"id":"7256","type":"CID","arg1_id":"7227","arg2_id":"7239","normalized":[]},{"id":"7257","type":"CID","arg1_id":"7227","arg2_id":"7243","normalized":[]},{"id":"7258","type":"CID","arg1_id":"7231","arg2_id":"7223","normalized":[]},{"id":"7259","type":"CID","arg1_id":"7231","arg2_id":"7224","normalized":[]},{"id":"7260","type":"CID","arg1_id":"7231","arg2_id":"7226","normalized":[]},{"id":"7261","type":"CID","arg1_id":"7231","arg2_id":"7229","normalized":[]},{"id":"7262","type":"CID","arg1_id":"7231","arg2_id":"7230","normalized":[]},{"id":"7263","type":"CID","arg1_id":"7231","arg2_id":"7239","normalized":[]},{"id":"7264","type":"CID","arg1_id":"7231","arg2_id":"7243","normalized":[]},{"id":"7265","type":"CID","arg1_id":"7235","arg2_id":"7223","normalized":[]},{"id":"7266","type":"CID","arg1_id":"7235","arg2_id":"7224","normalized":[]},{"id":"7267","type":"CID","arg1_id":"7235","arg2_id":"7226","normalized":[]},{"id":"7268","type":"CID","arg1_id":"7235","arg2_id":"7229","normalized":[]},{"id":"7269","type":"CID","arg1_id":"7235","arg2_id":"7230","normalized":[]},{"id":"7270","type":"CID","arg1_id":"7235","arg2_id":"7239","normalized":[]},{"id":"7271","type":"CID","arg1_id":"7235","arg2_id":"7243","normalized":[]},{"id":"7272","type":"CID","arg1_id":"7240","arg2_id":"7223","normalized":[]},{"id":"7273","type":"CID","arg1_id":"7240","arg2_id":"7224","normalized":[]},{"id":"7274","type":"CID","arg1_id":"7240","arg2_id":"7226","normalized":[]},{"id":"7275","type":"CID","arg1_id":"7240","arg2_id":"7229","normalized":[]},{"id":"7276","type":"CID","arg1_id":"7240","arg2_id":"7230","normalized":[]},{"id":"7277","type":"CID","arg1_id":"7240","arg2_id":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{"id":"7342","document_id":"11587867","passages":[{"id":"7343","type":"title","text":["Fatal myeloencephalopathy due to accidental intrathecal vincristin administration: a report of two cases."],"offsets":[[0,105]]},{"id":"7344","type":"abstract","text":["We report on two fatal cases of accidental intrathecal vincristine instillation in a 5-year old girl with recurrent acute lymphoblastic leucemia and a 57-year old man with lymphoblastic lymphoma. The girl died seven days, the man four weeks after intrathecal injection of vincristine. Clinically, the onset was characterized by the signs of opistothonus, sensory and motor dysfunction and ascending paralysis. Histological and immunohistochemical investigations (HE-LFB, CD-68, Neurofilament) revealed degeneration of myelin and axons as well as pseudocystic transformation in areas exposed to vincristine, accompanied by secondary changes with numerous prominent macrophages. The clinical course and histopathological results of the two cases are presented. A review of all reported cases in the literature is given. A better controlled regimen for administering vincristine and intrathecal chemotherapy is recommended."],"offsets":[[106,1026]]}],"entities":[{"id":"7345","type":"Disease","text":["myeloencephalopathy"],"offsets":[[6,25]],"normalized":[{"db_name":"MESH","db_id":"D001927"}]},{"id":"7346","type":"Chemical","text":["vincristin"],"offsets":[[56,66]],"normalized":[{"db_name":"MESH","db_id":"D014750"}]},{"id":"7347","type":"Chemical","text":["vincristine"],"offsets":[[161,172]],"normalized":[{"db_name":"MESH","db_id":"D014750"}]},{"id":"7348","type":"Disease","text":["acute lymphoblastic leucemia"],"offsets":[[222,250]],"normalized":[{"db_name":"MESH","db_id":"D054198"}]},{"id":"7349","type":"Disease","text":["lymphoblastic lymphoma"],"offsets":[[278,300]],"normalized":[{"db_name":"MESH","db_id":"D054198"}]},{"id":"7350","type":"Chemical","text":["vincristine"],"offsets":[[378,389]],"normalized":[{"db_name":"MESH","db_id":"D014750"}]},{"id":"7351","type":"Disease","text":["opistothonus, sensory and motor dysfunction"],"offsets":[[447,490]],"normalized":[{"db_name":"MESH","db_id":"D020258"},{"db_name":"MESH","db_id":"D020258"},{"db_name":"MESH","db_id":"D020258"}]},{"id":"7352","type":"Disease","text":["opistothonus","dysfunction"],"offsets":[[447,459],[478,489]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"7353","type":"Disease","text":["sensory","dysfunction"],"offsets":[[461,468],[479,490]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"7354","type":"Disease","text":["motor dysfunction"],"offsets":[[473,490]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"7355","type":"Disease","text":["paralysis"],"offsets":[[505,514]],"normalized":[{"db_name":"MESH","db_id":"D010243"}]},{"id":"7356","type":"Disease","text":["degeneration of myelin and axons"],"offsets":[[608,640]],"normalized":[{"db_name":"MESH","db_id":"D003711"},{"db_name":"MESH","db_id":"D009410"}]},{"id":"7357","type":"Disease","text":["degeneration of myelin"],"offsets":[[608,630]],"normalized":[{"db_name":"MESH","db_id":"D003711"}]},{"id":"7358","type":"Disease","text":["degeneration of","axons"],"offsets":[[608,623],[635,640]],"normalized":[{"db_name":"MESH","db_id":"D009410"}]},{"id":"7359","type":"Disease","text":["pseudocystic transformation"],"offsets":[[652,679]],"normalized":[]},{"id":"7360","type":"Chemical","text":["vincristine"],"offsets":[[700,711]],"normalized":[{"db_name":"MESH","db_id":"D014750"}]},{"id":"7361","type":"Chemical","text":["vincristine"],"offsets":[[970,981]],"normalized":[{"db_name":"MESH","db_id":"D014750"}]}],"events":[],"coreferences":[],"relations":[{"id":"7362","type":"CID","arg1_id":"7346","arg2_id":"7351","normalized":[]},{"id":"7363","type":"CID","arg1_id":"7346","arg2_id":"7351","normalized":[]},{"id":"7364","type":"CID","arg1_id":"7346","arg2_id":"7351","normalized":[]},{"id":"7365","type":"CID","arg1_id":"7346","arg2_id":"7352","normalized":[]},{"id":"7366","type":"CID","arg1_id":"7346","arg2_id":"7353","normalized":[]},{"id":"7367","type":"CID","arg1_id":"7346","arg2_id":"7354","normalized":[]},{"id":"7368","type":"CID","arg1_id":"7347","arg2_id":"7351","normalized":[]},{"id":"7369","type":"CID","arg1_id":"7347","arg2_id":"7351","normalized":[]},{"id":"7370","type":"CID","arg1_id":"7347","arg2_id":"7351","normalized":[]},{"id":"7371","type":"CID","arg1_id":"7347","arg2_id":"7352","normalized":[]},{"id":"7372","type":"CID","arg1_id":"7347","arg2_id":"7353","normalized":[]},{"id":"7373","type":"CID","arg1_id":"7347","arg2_id":"7354","normalized":[]},{"id":"7374","type":"CID","arg1_id":"7350","arg2_id":"7351","normalized":[]},{"id":"7375","type":"CID","arg1_id":"7350","arg2_id":"7351","normalized":[]},{"id":"7376","type":"CID","arg1_id":"7350","arg2_id":"7351","normalized":[]},{"id":"7377","type":"CID","arg1_id":"7350","arg2_id":"7352","normalized":[]},{"id":"7378","type":"CID","arg1_id":"7350","arg2_id":"7353","normalized":[]},{"id":"7379","type":"CID","arg1_id":"7350","arg2_id":"7354","normalized":[]},{"id":"7380","type":"CID","arg1_id":"7360","arg2_id":"7351","normalized":[]},{"id":"7381","type":"CID","arg1_id":"7360","arg2_id":"7351","normalized":[]},{"id":"7382","type":"CID","arg1_id":"7360","arg2_id":"7351","normalized":[]},{"id":"7383","type":"CID","arg1_id":"7360","arg2_id":"7352","normalized":[]},{"id":"7384","type":"CID","arg1_id":"7360","arg2_id":"7353","normalized":[]},{"id":"7385","type":"CID","arg1_id":"7360","arg2_id":"7354","normalized":[]},{"id":"7386","type":"CID","arg1_id":"7361","arg2_id":"7351","normalized":[]},{"id":"7387","type":"CID","arg1_id":"7361","arg2_id":"7351","normalized":[]},{"id":"7388","type":"CID","arg1_id":"7361","arg2_id":"7351","normalized":[]},{"id":"7389","type":"CID","arg1_id":"7361","arg2_id":"7352","normalized":[]},{"id":"7390","type":"CID","arg1_id":"7361","arg2_id":"7353","normalized":[]},{"id":"7391","type":"CID","arg1_id":"7361","arg2_id":"7354","normalized":[]},{"id":"7392","type":"CID","arg1_id":"7346","arg2_id":"7356","normalized":[]},{"id":"7393","type":"CID","arg1_id":"7346","arg2_id":"7358","normalized":[]},{"id":"7394","type":"CID","arg1_id":"7347","arg2_id":"7356","normalized":[]},{"id":"7395","type":"CID","arg1_id":"7347","arg2_id":"7358","normalized":[]},{"id":"7396","type":"CID","arg1_id":"7350","arg2_id":"7356","normalized":[]},{"id":"7397","type":"CID","arg1_id":"7350","arg2_id":"7358","normalized":[]},{"id":"7398","type":"CID","arg1_id":"7360","arg2_id":"7356","normalized":[]},{"id":"7399","type":"CID","arg1_id":"7360","arg2_id":"7358","normalized":[]},{"id":"7400","type":"CID","arg1_id":"7361","arg2_id":"7356","normalized":[]},{"id":"7401","type":"CID","arg1_id":"7361","arg2_id":"7358","normalized":[]},{"id":"7402","type":"CID","arg1_id":"7346","arg2_id":"7356","normalized":[]},{"id":"7403","type":"CID","arg1_id":"7346","arg2_id":"7357","normalized":[]},{"id":"7404","type":"CID","arg1_id":"7347","arg2_id":"7356","normalized":[]},{"id":"7405","type":"CID","arg1_id":"7347","arg2_id":"7357","normalized":[]},{"id":"7406","type":"CID","arg1_id":"7350","arg2_id":"7356","normalized":[]},{"id":"7407","type":"CID","arg1_id":"7350","arg2_id":"7357","normalized":[]},{"id":"7408","type":"CID","arg1_id":"7360","arg2_id":"7356","normalized":[]},{"id":"7409","type":"CID","arg1_id":"7360","arg2_id":"7357","normalized":[]},{"id":"7410","type":"CID","arg1_id":"7361","arg2_id":"7356","normalized":[]},{"id":"7411","type":"CID","arg1_id":"7361","arg2_id":"7357","normalized":[]}]}
{"id":"7412","document_id":"11679859","passages":[{"id":"7413","type":"title","text":["Intravenous administration of prochlorperazine by 15-minute infusion versus 2-minute bolus does not affect the incidence of akathisia: a prospective, randomized, controlled trial."],"offsets":[[0,179]]},{"id":"7414","type":"abstract","text":["STUDY OBJECTIVE: We sought to compare the rate of akathisia after administration of intravenous prochlorperazine as a 2-minute bolus or 15-minute infusion. METHODS: We conducted a prospective, randomized, double-blind study in the emergency department of a central-city teaching hospital. Patients aged 18 years or older treated with prochlorperazine for headache, nausea, or vomiting were eligible for inclusion. Study participants were randomized to receive 10 mg of prochlorperazine administered intravenously by means of 2-minute push (bolus group) or 10 mg diluted in 50 mL of normal saline solution administered by means of intravenous infusion during a 15-minute period (infusion group). The main outcome was the number of study participants experiencing akathisia within 60 minutes of administration. Akathisia was defined as either a spontaneous report of restlessness or agitation or a change of 2 or more in the patient-reported akathisia rating scale and a change of at least 1 in the investigator-observed akathisia rating scale. The intensity of headache and nausea was measured with a 100-mm visual analog scale. RESULTS: One hundred patients were enrolled. One study participant was excluded after protocol violation. Seventy-three percent (73\/99) of the study participants were treated for headache and 70% (70\/99) for nausea. In the bolus group, 26.0% (13\/50) had akathisia compared with 32.7% (16\/49) in the infusion group (Delta=-6.7%; 95% confidence interval [CI] -24.6% to 11.2%). The difference between the bolus and infusion groups in the percentage of participants who saw a 50% reduction in their headache intensity within 30 minutes was 11.8% (95% CI -9.6% to 33.3%). The difference in the percentage of patients with a 50% reduction in their nausea was 12.6% (95% CI -4.6% to 29.8%). CONCLUSION: A 50% reduction in the incidence of akathisia when prochlorperazine was administered by means of 15-minute intravenous infusion versus a 2-minute intravenous push was not detected. The efficacy of prochlorperazine in the treatment of headache and nausea likewise did not appear to be affected by the rate of administration, although no formal statistical comparisons were made."],"offsets":[[180,2381]]}],"entities":[{"id":"7415","type":"Chemical","text":["prochlorperazine"],"offsets":[[30,46]],"normalized":[{"db_name":"MESH","db_id":"D011346"}]},{"id":"7416","type":"Disease","text":["akathisia"],"offsets":[[124,133]],"normalized":[{"db_name":"MESH","db_id":"D017109"}]},{"id":"7417","type":"Disease","text":["akathisia"],"offsets":[[230,239]],"normalized":[{"db_name":"MESH","db_id":"D017109"}]},{"id":"7418","type":"Chemical","text":["prochlorperazine"],"offsets":[[276,292]],"normalized":[{"db_name":"MESH","db_id":"D011346"}]},{"id":"7419","type":"Chemical","text":["prochlorperazine"],"offsets":[[514,530]],"normalized":[{"db_name":"MESH","db_id":"D011346"}]},{"id":"7420","type":"Disease","text":["headache"],"offsets":[[535,543]],"normalized":[{"db_name":"MESH","db_id":"D006261"}]},{"id":"7421","type":"Disease","text":["nausea"],"offsets":[[545,551]],"normalized":[{"db_name":"MESH","db_id":"D009325"}]},{"id":"7422","type":"Disease","text":["vomiting"],"offsets":[[556,564]],"normalized":[{"db_name":"MESH","db_id":"D014839"}]},{"id":"7423","type":"Chemical","text":["prochlorperazine"],"offsets":[[649,665]],"normalized":[{"db_name":"MESH","db_id":"D011346"}]},{"id":"7424","type":"Disease","text":["akathisia"],"offsets":[[942,951]],"normalized":[{"db_name":"MESH","db_id":"D017109"}]},{"id":"7425","type":"Disease","text":["agitation"],"offsets":[[1061,1070]],"normalized":[{"db_name":"MESH","db_id":"D011595"}]},{"id":"7426","type":"Disease","text":["akathisia"],"offsets":[[1120,1129]],"normalized":[{"db_name":"MESH","db_id":"D017109"}]},{"id":"7427","type":"Disease","text":["akathisia"],"offsets":[[1199,1208]],"normalized":[{"db_name":"MESH","db_id":"D017109"}]},{"id":"7428","type":"Disease","text":["headache"],"offsets":[[1240,1248]],"normalized":[{"db_name":"MESH","db_id":"D006261"}]},{"id":"7429","type":"Disease","text":["nausea"],"offsets":[[1253,1259]],"normalized":[{"db_name":"MESH","db_id":"D009325"}]},{"id":"7430","type":"Disease","text":["headache"],"offsets":[[1487,1495]],"normalized":[{"db_name":"MESH","db_id":"D006261"}]},{"id":"7431","type":"Disease","text":["nausea"],"offsets":[[1516,1522]],"normalized":[{"db_name":"MESH","db_id":"D009325"}]},{"id":"7432","type":"Disease","text":["akathisia"],"offsets":[[1562,1571]],"normalized":[{"db_name":"MESH","db_id":"D017109"}]},{"id":"7433","type":"Disease","text":["headache"],"offsets":[[1803,1811]],"normalized":[{"db_name":"MESH","db_id":"D006261"}]},{"id":"7434","type":"Disease","text":["nausea"],"offsets":[[1950,1956]],"normalized":[{"db_name":"MESH","db_id":"D009325"}]},{"id":"7435","type":"Disease","text":["akathisia"],"offsets":[[2040,2049]],"normalized":[{"db_name":"MESH","db_id":"D017109"}]},{"id":"7436","type":"Chemical","text":["prochlorperazine"],"offsets":[[2055,2071]],"normalized":[{"db_name":"MESH","db_id":"D011346"}]},{"id":"7437","type":"Chemical","text":["prochlorperazine"],"offsets":[[2201,2217]],"normalized":[{"db_name":"MESH","db_id":"D011346"}]},{"id":"7438","type":"Disease","text":["headache"],"offsets":[[2238,2246]],"normalized":[{"db_name":"MESH","db_id":"D006261"}]},{"id":"7439","type":"Disease","text":["nausea"],"offsets":[[2251,2257]],"normalized":[{"db_name":"MESH","db_id":"D009325"}]}],"events":[],"coreferences":[],"relations":[{"id":"7440","type":"CID","arg1_id":"7415","arg2_id":"7416","normalized":[]},{"id":"7441","type":"CID","arg1_id":"7415","arg2_id":"7417","normalized":[]},{"id":"7442","type":"CID","arg1_id":"7415","arg2_id":"7424","normalized":[]},{"id":"7443","type":"CID","arg1_id":"7415","arg2_id":"7426","normalized":[]},{"id":"7444","type":"CID","arg1_id":"7415","arg2_id":"7427","normalized":[]},{"id":"7445","type":"CID","arg1_id":"7415","arg2_id":"7432","normalized":[]},{"id":"7446","type":"CID","arg1_id":"7415","arg2_id":"7435","normalized":[]},{"id":"7447","type":"CID","arg1_id":"7418","arg2_id":"7416","normalized":[]},{"id":"7448","type":"CID","arg1_id":"7418","arg2_id":"7417","normalized":[]},{"id":"7449","type":"CID","arg1_id":"7418","arg2_id":"7424","normalized":[]},{"id":"7450","type":"CID","arg1_id":"7418","arg2_id":"7426","normalized":[]},{"id":"7451","type":"CID","arg1_id":"7418","arg2_id":"7427","normalized":[]},{"id":"7452","type":"CID","arg1_id":"7418","arg2_id":"7432","normalized":[]},{"id":"7453","type":"CID","arg1_id":"7418","arg2_id":"7435","normalized":[]},{"id":"7454","type":"CID","arg1_id":"7419","arg2_id":"7416","normalized":[]},{"id":"7455","type":"CID","arg1_id":"7419","arg2_id":"7417","normalized":[]},{"id":"7456","type":"CID","arg1_id":"7419","arg2_id":"7424","normalized":[]},{"id":"7457","type":"CID","arg1_id":"7419","arg2_id":"7426","normalized":[]},{"id":"7458","type":"CID","arg1_id":"7419","arg2_id":"7427","normalized":[]},{"id":"7459","type":"CID","arg1_id":"7419","arg2_id":"7432","normalized":[]},{"id":"7460","type":"CID","arg1_id":"7419","arg2_id":"7435","normalized":[]},{"id":"7461","type":"CID","arg1_id":"7423","arg2_id":"7416","normalized":[]},{"id":"7462"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{"id":"7482","document_id":"12041669","passages":[{"id":"7483","type":"title","text":["Antithymocyte globulin in the treatment of D-penicillamine-induced aplastic anemia."],"offsets":[[0,83]]},{"id":"7484","type":"abstract","text":["A patient who received antithymocyte globulin therapy for aplastic anemia due to D-penicillamine therapy is described. Bone marrow recovery and peripheral blood recovery were complete 1 month and 3 months, respectively, after treatment, and blood transfusion or other therapies were not necessary in a follow-up period of more than 2 years. Use of antithymocyte globulin may be the optimal treatment of D-penicillamine-induced aplastic anemia."],"offsets":[[84,527]]}],"entities":[{"id":"7485","type":"Chemical","text":["Antithymocyte globulin"],"offsets":[[0,22]],"normalized":[{"db_name":"MESH","db_id":"D000961"}]},{"id":"7486","type":"Chemical","text":["D-penicillamine"],"offsets":[[43,58]],"normalized":[{"db_name":"MESH","db_id":"D010396"}]},{"id":"7487","type":"Disease","text":["aplastic anemia"],"offsets":[[67,82]],"normalized":[{"db_name":"MESH","db_id":"D000741"}]},{"id":"7488","type":"Chemical","text":["antithymocyte globulin"],"offsets":[[107,129]],"normalized":[{"db_name":"MESH","db_id":"D000961"}]},{"id":"7489","type":"Disease","text":["aplastic anemia"],"offsets":[[142,157]],"normalized":[{"db_name":"MESH","db_id":"D000741"}]},{"id":"7490","type":"Chemical","text":["D-penicillamine"],"offsets":[[165,180]],"normalized":[{"db_name":"MESH","db_id":"D010396"}]},{"id":"7491","type":"Chemical","text":["antithymocyte globulin"],"offsets":[[432,454]],"normalized":[{"db_name":"MESH","db_id":"D000961"}]},{"id":"7492","type":"Chemical","text":["D-penicillamine"],"offsets":[[487,502]],"normalized":[{"db_name":"MESH","db_id":"D010396"}]},{"id":"7493","type":"Disease","text":["aplastic anemia"],"offsets":[[511,526]],"normalized":[{"db_name":"MESH","db_id":"D000741"}]}],"events":[],"coreferences":[],"relations":[{"id":"7494","type":"CID","arg1_id":"7486","arg2_id":"7487","normalized":[]},{"id":"7495","type":"CID","arg1_id":"7486","arg2_id":"7489","normalized":[]},{"id":"7496","type":"CID","arg1_id":"7486","arg2_id":"7493","normalized":[]},{"id":"7497","type":"CID","arg1_id":"7490","arg2_id":"7487","normalized":[]},{"id":"7498","type":"CID","arg1_id":"7490","arg2_id":"7489","normalized":[]},{"id":"7499","type":"CID","arg1_id":"7490","arg2_id":"7493","normalized":[]},{"id":"7500","type":"CID","arg1_id":"7492","arg2_id":"7487","normalized":[]},{"id":"7501","type":"CID","arg1_id":"7492","arg2_id":"7489","normalized":[]},{"id":"7502","type":"CID","arg1_id":"7492","arg2_id":"7493","normalized":[]}]}
{"id":"7503","document_id":"12198388","passages":[{"id":"7504","type":"title","text":["The relationship between hippocampal acetylcholine release and cholinergic convulsant sensitivity in withdrawal seizure-prone and withdrawal seizure-resistant selected mouse lines."],"offsets":[[0,180]]},{"id":"7505","type":"abstract","text":["BACKGROUND: The septo-hippocampal cholinergic pathway has been implicated in epileptogenesis, and genetic factors influence the response to cholinergic agents, but limited data are available on cholinergic involvement in alcohol withdrawal severity. Thus, the relationship between cholinergic activity and responsiveness and alcohol withdrawal was investigated in a genetic animal model of ethanol withdrawal severity. METHODS: Cholinergic convulsant sensitivity was examined in alcohol-na  ve Withdrawal Seizure-Prone (WSP) and-Resistant (WSR) mice. Animals were administered nicotine, carbachol, or neostigmine via timed tail vein infusion, and the latencies to onset of tremor and clonus were recorded and converted to threshold dose. We also used microdialysis to measure basal and potassium-stimulated acetylcholine (ACh) release in the CA1 region of the hippocampus. Potassium was applied by reverse dialysis twice, separated by 75 min. Hippocampal ACh also was measured during testing for handling-induced convulsions. RESULTS: Sensitivity to several convulsion endpoints induced by nicotine, carbachol, and neostigmine were significantly greater in WSR versus WSP mice. In microdialysis experiments, the lines did not differ in basal release of ACh, and 50 mM KCl increased ACh output in both lines of mice. However, the increase in release of ACh produced by the first application of KCl was 2-fold higher in WSP versus WSR mice. When hippocampal ACh was measured during testing for handling-induced convulsions, extracellular ACh was significantly elevated (192%) in WSP mice, but was nonsignificantly elevated (59%) in WSR mice. CONCLUSIONS: These results suggest that differences in cholinergic activity and postsynaptic sensitivity to cholinergic convulsants may be associated with ethanol withdrawal severity and implicate cholinergic mechanisms in alcohol withdrawal. Specifically, WSP mice may have lower sensitivity to cholinergic convulsants compared with WSR because of postsynaptic receptor desensitization brought on by higher activity of cholinergic 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{"id":"7588","document_id":"12574103","passages":[{"id":"7589","type":"title","text":["Prenatal dexamethasone programs hypertension and renal injury in the rat."],"offsets":[[0,73]]},{"id":"7590","type":"abstract","text":["Dexamethasone is frequently administered to the developing fetus to accelerate pulmonary development. The purpose of the present study was to determine if prenatal dexamethasone programmed a progressive increase in blood pressure and renal injury in rats. Pregnant rats were given either vehicle or 2 daily intraperitoneal injections of dexamethasone (0.2 mg\/kg body weight) on gestational days 11 and 12, 13 and 14, 15 and 16, 17 and 18, or 19 and 20. Offspring of rats administered dexamethasone on days 15 and 16 gestation had a 20% reduction in glomerular number compared with control at 6 to 9 months of age (22 527+\/-509 versus 28 050+\/-561, P<0.05), which was comparable to the percent reduction in glomeruli measured at 3 weeks of age. Six- to 9-month old rats receiving prenatal dexamethasone on days 17 and 18 of gestation had a 17% reduction in glomeruli (23 380+\/-587) compared with control rats (P<0.05). Male rats that received prenatal dexamethasone on days 15 and 16, 17 and 18, and 13 and 14 of gestation had elevated blood pressures at 6 months of age; the latter group did not have a reduction in glomerular number. Adult rats given dexamethasone on days 15 and 16 of gestation had more glomeruli with glomerulosclerosis than control rats. This study shows that prenatal dexamethasone in rats results in a reduction in glomerular number, glomerulosclerosis, and hypertension when administered at specific points during gestation. Hypertension was observed in animals that had a reduction in glomeruli as well as in a group that did not have a reduction in glomerular number, suggesting that a reduction in glomerular number is not the sole cause for the development of hypertension."],"offsets":[[74,1775]]}],"entities":[{"id":"7591","type":"Chemical","text":["dexamethasone"],"offsets":[[9,22]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"7592","type":"Disease","text":["hypertension"],"offsets":[[32,44]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"7593","type":"Disease","text":["renal injury"],"offsets":[[49,61]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"7594","type":"Chemical","text":["dexamethasone"],"offsets":[[238,251]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"7595","type":"Disease","text":["increase in blood pressure"],"offsets":[[277,303]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"7596","type":"Disease","text":["renal 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{"id":"7718","document_id":"12615818","passages":[{"id":"7719","type":"title","text":["The risk of venous thromboembolism in women prescribed cyproterone acetate in combination with ethinyl estradiol: a nested cohort analysis and case-control study."],"offsets":[[0,162]]},{"id":"7720","type":"abstract","text":["BACKGROUND: Cyproterone acetate combined with ethinyl estradiol (CPA\/EE) is licensed in the UK for the treatment of women with acne and hirsutism and is also a treatment option for polycystic ovary syndrome (PCOS). Previous studies have demonstrated an increased risk of venous thromboembolism (VTE) associated with CPA\/EE compared with conventional combined oral contraceptives (COCs). We believe the results of those studies may have been affected by residual confounding. METHODS: Using the General Practice Research Database we conducted a cohort analysis and case-control study nested within a population of women aged between 15 and 39 years with acne, hirsutism or PCOS to estimate the risk of VTE associated with CPA\/EE. RESULTS: The age-adjusted incidence rate ratio for CPA\/EE versus conventional COCs was 2.20 [95% confidence interval (CI) 1.35-3.58]. Using as the reference group women who were not using oral contraception, had no recent pregnancy or menopausal symptoms, the case-control analysis gave an adjusted odds ratio (OR(adj)) of 7.44 (95% CI 3.67-15.08) for CPA\/EE use compared with an OR(adj) of 2.58 (95% CI 1.60-4.18) for use of conventional COCs. CONCLUSIONS: We have demonstrated an increased risk of VTE associated with the use of CPA\/EE in women with acne, hirsutism or PCOS although residual confounding by indication cannot be excluded."],"offsets":[[163,1531]]}],"entities":[{"id":"7721","type":"Disease","text":["venous thromboembolism"],"offsets":[[12,34]],"normalized":[{"db_name":"MESH","db_id":"D054556"}]},{"id":"7722","type":"Chemical","text":["cyproterone acetate"],"offsets":[[55,74]],"normalized":[{"db_name":"MESH","db_id":"D017373"}]},{"id":"7723","type":"Chemical","text":["ethinyl estradiol"],"offsets":[[95,112]],"normalized":[{"db_name":"MESH","db_id":"D004997"}]},{"id":"7724","type":"Chemical","text":["Cyproterone acetate"],"offsets":[[175,194]],"normalized":[{"db_name":"MESH","db_id":"D017373"}]},{"id":"7725","type":"Chemical","text":["ethinyl 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{"id":"7833","document_id":"12789195","passages":[{"id":"7834","type":"title","text":["Pseudoacromegaly induced by the long-term use of minoxidil."],"offsets":[[0,59]]},{"id":"7835","type":"abstract","text":["Acromegaly is an endocrine disorder caused by chronic excessive growth hormone secretion from the anterior pituitary gland. Significant disfiguring changes occur as a result of bone, cartilage, and soft tissue hypertrophy, including the thickening of the skin, coarsening of facial features, and cutis verticis gyrata. Pseudoacromegaly, on the other hand, is the presence of similar acromegaloid features in the absence of elevated growth hormone or insulin-like growth factor levels. We present a patient with pseudoacromegaly that resulted from the long-term use of minoxidil at an unusually high dose. This is the first case report of pseudoacromegaly as a side effect of minoxidil use."],"offsets":[[60,749]]}],"entities":[{"id":"7836","type":"Disease","text":["Pseudoacromegaly"],"offsets":[[0,16]],"normalized":[{"db_name":"MESH","db_id":"D004194"}]},{"id":"7837","type":"Chemical","text":["minoxidil"],"offsets":[[49,58]],"normalized":[{"db_name":"MESH","db_id":"D008914"}]},{"id":"7838","type":"Disease","text":["Acromegaly"],"offsets":[[60,70]],"normalized":[{"db_name":"MESH","db_id":"D000172"}]},{"id":"7839","type":"Disease","text":["endocrine disorder"],"offsets":[[77,95]],"normalized":[{"db_name":"MESH","db_id":"D004700"}]},{"id":"7840","type":"Disease","text":["hypertrophy"],"offsets":[[270,281]],"normalized":[{"db_name":"MESH","db_id":"D006984"}]},{"id":"7841","type":"Disease","text":["cutis verticis gyrata"],"offsets":[[356,377]],"normalized":[{"db_name":"MESH","db_id":"C535610"}]},{"id":"7842","type":"Disease","text":["Pseudoacromegaly"],"offsets":[[379,395]],"normalized":[{"db_name":"MESH","db_id":"D004194"}]},{"id":"7843","type":"Disease","text":["pseudoacromegaly"],"offsets":[[571,587]],"normalized":[{"db_name":"MESH","db_id":"D004194"}]},{"id":"7844","type":"Chemical","text":["minoxidil"],"offsets":[[628,637]],"normalized":[{"db_name":"MESH","db_id":"D008914"}]},{"id":"7845","type":"Disease","text":["pseudoacromegaly"],"offsets":[[698,714]],"normalized":[{"db_name":"MESH","db_id":"D004194"}]},{"id":"7846","type":"Chemical","text":["minoxidil"],"offsets":[[735,744]],"normalized":[{"db_name":"MESH","db_id":"D008914"}]}],"events":[],"coreferences":[],"relations":[{"id":"7847","type":"CID","arg1_id":"7837","arg2_id":"7838","normalized":[]},{"id":"7848","type":"CID","arg1_id":"7844","arg2_id":"7838","normalized":[]},{"id":"7849","type":"CID","arg1_id":"7846","arg2_id":"7838","normalized":[]}]}
{"id":"7850","document_id":"12820454","passages":[{"id":"7851","type":"title","text":["Combined androgen blockade-induced anemia in prostate cancer patients without bone involvement."],"offsets":[[0,95]]},{"id":"7852","type":"abstract","text":["BACKGROUND: To determine the onset and extent of combined androgen blockade (CAB)-induced anemia in prostate cancer patients without bone involvement. PATIENTS AND METHODS: Forty-two patients with biopsy-proven prostatic adenocarcinoma [26 with stage C (T3N0M0) and 16 with stage D1 (T3N1M0)] were included in this study. All patients received CAB [leuprolide acetate (LHRH-A) 3.75 mg, intramuscularly, every 28 days plus 250 mg flutamide, tid, per Os] and were evaluated for anemia by physical examination and laboratory tests at baseline and 4 subsequent intervals (1, 2, 3 and 6 months post-CAB). Hb, PSA and Testosterone measurements were recorded. Patients with stage D2-3 disease, abnormal hemoglobin level or renal and liver function tests that were higher than the upper limits were excluded from the study. The duration of the study was six months. RESULTS: The mean hemoglobin (Hb) levels were significantly declined in all patients from baseline of 14.2 g\/dl to 14.0 g\/dl, 13.5 g\/dl, 13.2 g\/dl and 12.7 g\/dl at 1, 2, 3 and 6 months post-CAB, respectively. Severe and clinically evident anemia of Hb < 11 g\/dl with clinical symptoms was detected in 6 patients (14.3%). This CAB-induced anemia was normochromic and normocytic. At six months post-CAB, patients with severe anemia had a Hb mean value of 10.2 +\/- 0.1 g\/dl (X +\/- SE), whereas the other patients had mild anemia with Hb mean value of 13.2 +\/- 0.17 (X +\/- SE). The development of severe anemia at 6 months post-CAB was predictable by the reduction of Hb baseline value of more than 2.5 g\/dl after 3 months of CAB (p = 0.01). The development of severe CAB-induced anemia in prostate cancer patients did not correlate with T baseline values (T < 3 ng\/ml versus T > or = 3 ng\/ml), with age (< 76 yrs versus > or = 76 yrs), and clinical stage (stage C versus stage D1). Severe and clinically evident anemia was easily corrected by subcutaneous injections (3 times\/week for 1 month) of recombinant erythropoietin (rHuEPO-beta). CONCLUSION: Our data suggest that rHuEPO-beta correctable CAB-induced anemia occurs in 14.3% of prostate cancer patients after 6 months of therapy."],"offsets":[[96,2237]]}],"entities":[{"id":"7853","type":"Disease","text":["anemia"],"offsets":[[35,41]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]},{"id":"7854","type":"Disease","text":["prostate cancer"],"offsets":[[45,60]],"normalized":[{"db_name":"MESH","db_id":"D011471"}]},{"id":"7855","type":"Disease","text":["anemia"],"offsets":[[186,192]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]},{"id":"7856","type":"Disease","text":["prostate cancer"],"offsets":[[196,211]],"normalized":[{"db_name":"MESH","db_id":"D011471"}]},{"id":"7857","type":"Disease","text":["prostatic adenocarcinoma"],"offsets":[[307,331]],"normalized":[{"db_name":"MESH","db_id":"D000230"}]},{"id":"7858","type":"Chemical","text":["leuprolide 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{"id":"7906","document_id":"14657095","passages":[{"id":"7907","type":"title","text":["Reversible dilated cardiomyopathy related to amphotericin B therapy."],"offsets":[[0,68]]},{"id":"7908","type":"abstract","text":["We describe a patient who developed dilated cardiomyopathy and clinical congestive heart failure after 2 months of therapy with amphotericin B (AmB) for disseminated coccidioidomycosis. His echocardiographic abnormalities and heart failure resolved after posaconazole was substituted for AmB. It is important to recognize the rare and potentially reversible toxicity of AmB."],"offsets":[[69,443]]}],"entities":[{"id":"7909","type":"Disease","text":["dilated cardiomyopathy"],"offsets":[[11,33]],"normalized":[{"db_name":"MESH","db_id":"D002311"}]},{"id":"7910","type":"Chemical","text":["amphotericin B"],"offsets":[[45,59]],"normalized":[{"db_name":"MESH","db_id":"D000666"}]},{"id":"7911","type":"Disease","text":["dilated cardiomyopathy"],"offsets":[[105,127]],"normalized":[{"db_name":"MESH","db_id":"D002311"}]},{"id":"7912","type":"Disease","text":["heart failure"],"offsets":[[152,165]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]},{"id":"7913","type":"Chemical","text":["amphotericin B"],"offsets":[[197,211]],"normalized":[{"db_name":"MESH","db_id":"D000666"}]},{"id":"7914","type":"Chemical","text":["AmB"],"offsets":[[213,216]],"normalized":[{"db_name":"MESH","db_id":"D000666"}]},{"id":"7915","type":"Disease","text":["coccidioidomycosis"],"offsets":[[235,253]],"normalized":[{"db_name":"MESH","db_id":"D003047"}]},{"id":"7916","type":"Disease","text":["heart failure"],"offsets":[[295,308]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]},{"id":"7917","type":"Chemical","text":["posaconazole"],"offsets":[[324,336]],"normalized":[{"db_name":"MESH","db_id":"C101425"}]},{"id":"7918","type":"Chemical","text":["AmB"],"offsets":[[357,360]],"normalized":[{"db_name":"MESH","db_id":"D000666"}]},{"id":"7919","type":"Disease","text":["toxicity"],"offsets":[[427,435]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"7920","type":"Chemical","text":["AmB"],"offsets":[[439,442]],"normalized":[{"db_name":"MESH","db_id":"D000666"}]}],"events":[],"coreferences":[],"relations":[{"id":"7921","type":"CID","arg1_id":"7910","arg2_id":"7912","normalized":[]},{"id":"7922","type":"CID","arg1_id":"7910","arg2_id":"7916","normalized":[]},{"id":"7923","type":"CID","arg1_id":"7913","arg2_id":"7912","normalized":[]},{"id":"7924","type":"CID","arg1_id":"7913","arg2_id":"7916","normalized":[]},{"id":"7925","type":"CID","arg1_id":"7914","arg2_id":"7912","normalized":[]},{"id":"7926","type":"CID","arg1_id":"7914","arg2_id":"7916","normalized":[]},{"id":"7927","type":"CID","arg1_id":"7918","arg2_id":"7912","normalized":[]},{"id":"7928","type":"CID","arg1_id":"7918","arg2_id":"7916","normalized":[]},{"id":"7929","type":"CID","arg1_id":"7920","arg2_id":"7912","normalized":[]},{"id":"7930","type":"CID","arg1_id":"7920","arg2_id":"7916","normalized":[]},{"id":"7931","type":"CID","arg1_id":"7910","arg2_id":"7909","normalized":[]},{"id":"7932","type":"CID","arg1_id":"7910","arg2_id":"7911","normalized":[]},{"id":"7933","type":"CID","arg1_id":"7913","arg2_id":"7909","normalized":[]},{"id":"7934","type":"CID","arg1_id":"7913","arg2_id":"7911","normalized":[]},{"id":"7935","type":"CID","arg1_id":"7914","arg2_id":"7909","normalized":[]},{"id":"7936","type":"CID","arg1_id":"7914","arg2_id":"7911","normalized":[]},{"id":"7937","type":"CID","arg1_id":"7918","arg2_id":"7909","normalized":[]},{"id":"7938","type":"CID","arg1_id":"7918","arg2_id":"7911","normalized":[]},{"id":"7939","type":"CID","arg1_id":"7920","arg2_id":"7909","normalized":[]},{"id":"7940","type":"CID","arg1_id":"7920","arg2_id":"7911","normalized":[]}]}
{"id":"7941","document_id":"14765563","passages":[{"id":"7942","type":"title","text":["Risks of the consumption of beverages containing quinine."],"offsets":[[0,57]]},{"id":"7943","type":"abstract","text":["Although the United States Food and Drug Administration banned its use for nocturnal leg cramps due to lack of safety and efficacy, quinine is widely available in beverages including tonic water and bitter lemon. Numerous anecdotal reports suggest that products containing quinine may produce neurological complications, including confusion, altered mental status, seizures, and coma, particularly in older women. Psychologists need to inquire about consumption of quinine-containing beverages as part of an evaluation process."],"offsets":[[58,585]]}],"entities":[{"id":"7944","type":"Chemical","text":["quinine"],"offsets":[[49,56]],"normalized":[{"db_name":"MESH","db_id":"D011803"}]},{"id":"7945","type":"Disease","text":["nocturnal leg cramps"],"offsets":[[133,153]],"normalized":[{"db_name":"MESH","db_id":"D020922"}]},{"id":"7946","type":"Chemical","text":["quinine"],"offsets":[[190,197]],"normalized":[{"db_name":"MESH","db_id":"D011803"}]},{"id":"7947","type":"Chemical","text":["quinine"],"offsets":[[331,338]],"normalized":[{"db_name":"MESH","db_id":"D011803"}]},{"id":"7948","type":"Disease","text":["neurological complications"],"offsets":[[351,377]],"normalized":[{"db_name":"MESH","db_id":"D002493"}]},{"id":"7949","type":"Disease","text":["confusion"],"offsets":[[389,398]],"normalized":[{"db_name":"MESH","db_id":"D003221"}]},{"id":"7950","type":"Disease","text":["seizures"],"offsets":[[423,431]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"7951","type":"Disease","text":["coma"],"offsets":[[437,441]],"normalized":[{"db_name":"MESH","db_id":"D003128"}]},{"id":"7952","type":"Chemical","text":["quinine"],"offsets":[[523,530]],"normalized":[{"db_name":"MESH","db_id":"D011803"}]}],"events":[],"coreferences":[],"relations":[{"id":"7953","type":"CID","arg1_id":"7944","arg2_id":"7949","normalized":[]},{"id":"7954","type":"CID","arg1_id":"7946","arg2_id":"7949","normalized":[]},{"id":"7955","type":"CID","arg1_id":"7947","arg2_id":"7949","normalized":[]},{"id":"7956","type":"CID","arg1_id":"7952","arg2_id":"7949","normalized":[]},{"id":"7957","type":"CID","arg1_id":"7944","arg2_id":"7951","normalized":[]},{"id":"7958","type":"CID","arg1_id":"7946","arg2_id":"7951","normalized":[]},{"id":"7959","type":"CID","arg1_id":"7947","arg2_id":"7951","normalized":[]},{"id":"7960","type":"CID","arg1_id":"7952","arg2_id":"7951","normalized":[]},{"id":"7961","type":"CID","arg1_id":"7944","arg2_id":"7950","normalized":[]},{"id":"7962","type":"CID","arg1_id":"7946","arg2_id":"7950","normalized":[]},{"id":"7963","type":"CID","arg1_id":"7947","arg2_id":"7950","normalized":[]},{"id":"7964","type":"CID","arg1_id":"7952","arg2_id":"7950","normalized":[]}]}
{"id":"7965","document_id":"15036754","passages":[{"id":"7966","type":"title","text":["Organophosphate-induced convulsions and prevention of neuropathological damages."],"offsets":[[0,80]]},{"id":"7967","type":"abstract","text":["Such organophosphorus (OP) compounds as diisopropylfluorophosphate (DFP), sarin and soman are potent inhibitors of acetylcholinesterases (AChEs) and butyrylcholinesterases (BChEs). The acute toxicity of OPs is the result of their irreversible binding with AChEs in the central nervous system (CNS), which elevates acetylcholine (ACh) levels. The protective action of subcutaneously (SC) administered antidotes or their combinations in DFP (2.0 mg\/kg BW) intoxication was studied in 9-10-weeks-old Han-Wistar male rats. The rats received AChE reactivator pralidoxime-2-chloride (2PAM) (30.0 mg\/kg BW), anticonvulsant diazepam (2.0 mg\/kg BW), A(1)-adenosine receptor agonist N(6)-cyclopentyl adenosine (CPA) (2.0 mg\/kg BW), NMDA-receptor antagonist dizocilpine maleate (+-MK801 hydrogen maleate) (2.0 mg\/kg BW) or their combinations with cholinolytic drug atropine sulfate (50.0 mg\/kg BW) immediately or 30 min after the single SC injection of DFP. The control rats received atropine sulfate, but also saline and olive oil instead of other antidotes and DFP, respectively. All rats were terminated either 24 h or 3 weeks after the DFP injection. The rats treated with DFP-atropine showed severe typical OP-induced toxicity signs. When CPA, diazepam or 2PAM was given immediately after DFP-atropine, these treatments prevented, delayed or shortened the occurrence of serious signs of poisoning. Atropine-MK801 did not offer any additional protection against DFP toxicity. In conclusion, CPA, diazepam and 2PAM in combination with atropine prevented the occurrence of serious signs of poisoning and thus reduced the toxicity of DFP in rat."],"offsets":[[81,1716]]}],"entities":[{"id":"7968","type":"Chemical","text":["Organophosphate"],"offsets":[[0,15]],"normalized":[{"db_name":"MESH","db_id":"D010755"}]},{"id":"7969","type":"Disease","text":["convulsions"],"offsets":[[24,35]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"7970","type":"Disease","text":["neuropathological damages"],"offsets":[[54,79]],"normalized":[{"db_name":"MESH","db_id":"D004194"}]},{"id":"7971","type":"Chemical","text":["organophosphorus"],"offsets":[[86,102]],"normalized":[{"db_name":"MESH","db_id":"D010755"}]},{"id":"7972","type":"Chemical","text":["OP"],"offsets":[[104,106]],"normalized":[{"db_name":"MESH","db_id":"D010755"}]},{"id":"7973","type":"Chemical","text":["diisopropylfluorophosphate"],"offsets":[[121,147]],"normalized":[{"db_name":"MESH","db_id":"D007531"}]},{"id":"7974","type":"Chemical","text":["DFP"],"offsets":[[149,152]],"normalized":[{"db_name":"MESH","db_id":"D007531"}]},{"id":"7975","type":"Chemical","text":["sarin"],"offsets":[[155,160]],"normalized":[{"db_name":"MESH","db_id":"D012524"}]},{"id":"7976","type":"Chemical","text":["soman"],"offsets":[[165,170]],"normalized":[{"db_name":"MESH","db_id":"D012999"}]},{"id":"7977","type":"Disease","text":["toxicity"],"offsets":[[272,280]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"7978","type":"Chemical","text":["OPs"],"offsets":[[284,287]],"normalized":[{"db_name":"MESH","db_id":"D010755"}]},{"id":"7979","type":"Chemical","text":["acetylcholine"],"offsets":[[395,408]],"normalized":[{"db_name":"MESH","db_id":"D000109"}]},{"id":"7980","type":"Chemical","text":["ACh"],"offsets":[[410,413]],"normalized":[{"db_name":"MESH","db_id":"D000109"}]},{"id":"7981","type":"Chemical","text":["DFP"],"offsets":[[516,519]],"normalized":[{"db_name":"MESH","db_id":"D007531"}]},{"id":"7982","type":"Chemical","text":["pralidoxime-2-chloride"],"offsets":[[635,657]],"normalized":[{"db_name":"MESH","db_id":"D011220"}]},{"id":"7983","type":"Chemical","text":["2PAM"],"offsets":[[659,663]],"normalized":[{"db_name":"MESH","db_id":"D011220"}]},{"id":"7984","type":"Chemical","text":["diazepam"],"offsets":[[697,705]],"normalized":[{"db_name":"MESH","db_id":"D003975"}]},{"id":"7985","type":"Chemical","text":["adenosine"],"offsets":[[727,736]],"normalized":[{"db_name":"MESH","db_id":"D000241"}]},{"id":"7986","type":"Chemical","text":["N(6)-cyclopentyl adenosine"],"offsets":[[754,780]],"normalized":[{"db_name":"MESH","db_id":"C048599"}]},{"id":"7987","type":"Chemical","text":["CPA"],"offsets":[[782,785]],"normalized":[{"db_name":"MESH","db_id":"C048599"}]},{"id":"7988","type":"Chemical","text":["NMDA"],"offsets":[[803,807]],"normalized":[{"db_name":"MESH","db_id":"D016202"}]},{"id":"7989","type":"Chemical","text":["dizocilpine maleate"],"offsets":[[828,847]],"normalized":[{"db_name":"MESH","db_id":"D016291"}]},{"id":"7990","type":"Chemical","text":["atropine sulfate"],"offsets":[[935,951]],"normalized":[{"db_name":"MESH","db_id":"D001285"}]},{"id":"7991","type":"Chemical","text":["DFP"],"offsets":[[1023,1026]],"normalized":[{"db_name":"MESH","db_id":"D007531"}]},{"id":"7992","type":"Chemical","text":["atropine 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{"id":"8026","document_id":"15145918","passages":[{"id":"8027","type":"title","text":["Differential modulation by estrogen of alpha2-adrenergic and I1-imidazoline receptor-mediated hypotension in female rats."],"offsets":[[0,121]]},{"id":"8028","type":"abstract","text":["We have recently shown that estrogen negatively modulates the hypotensive effect of clonidine (mixed alpha2-\/I1-receptor agonist) in female rats and implicates the cardiovascular autonomic control in this interaction. The present study investigated whether this effect of estrogen involves interaction with alpha2- and\/or I1-receptors. Changes evoked by a single intraperitoneal injection of rilmenidine (600 microg\/kg) or alpha-methyldopa (100 mg\/kg), selective I1- and alpha2-receptor agonists, respectively, in blood pressure, hemodynamic variability, and locomotor activity were assessed in radiotelemetered sham-operated and ovariectomized (Ovx) Sprague-Dawley female rats with or without 12-wk estrogen replacement. Three time domain indexes of hemodynamic variability were employed: the standard deviation of mean arterial pressure as a measure of blood pressure variability and the standard deviation of beat-to-beat intervals (SDRR) and the root mean square of successive differences in R-wave-to-R-wave intervals as measures of heart rate variability. In sham-operated rats, rilmenidine or alpha-methyldopa elicited similar hypotension that lasted at least 5 h and was associated with reductions in standard deviation of mean arterial pressure. SDRR was reduced only by alpha-methyldopa. Ovx significantly enhanced the hypotensive response to alpha-methyldopa, in contrast to no effect on rilmenidine hypotension. The enhanced alpha-methyldopa hypotension in Ovx rats was paralleled with further reduction in SDRR and a reduced locomotor activity. Estrogen replacement (17beta-estradiol subcutaneous pellet, 14.2 microg\/day, 12 wk) of Ovx rats restored the hemodynamic and locomotor effects of alpha-methyldopa to sham-operated levels. These findings suggest that estrogen downregulates alpha2- but not I1-receptor-mediated hypotension and highlight a role for the cardiac autonomic control in alpha-methyldopa-estrogen interaction."],"offsets":[[122,2064]]}],"entities":[{"id":"8029","type":"Chemical","text":["estrogen"],"offsets":[[27,35]],"normalized":[{"db_name":"MESH","db_id":"D004967"}]},{"id":"8030","type":"Chemical","text":["imidazoline"],"offsets":[[64,75]],"normalized":[{"db_name":"MESH","db_id":"D048288"}]},{"id":"8031","type":"Disease","text":["hypotension"],"offsets":[[94,105]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"8032","type":"Chemical","text":["estrogen"],"offsets":[[150,158]],"normalized":[{"db_name":"MESH","db_id":"D004967"}]},{"id":"8033","type":"Disease","text":["hypotensive"],"offsets":[[184,195]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"8034","type":"Chemical","text":["clonidine"],"offsets":[[206,215]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]},{"id":"8035","type":"Chemical","text":["estrogen"],"offsets":[[394,402]],"normalized":[{"db_name":"MESH","db_id":"D004967"}]},{"id":"8036","type":"Chemical","text":["rilmenidine"],"offsets":[[514,525]],"normalized":[{"db_name":"MESH","db_id":"C032302"}]},{"id":"8037","type":"Chemical","text":["alpha-methyldopa"],"offsets":[[545,561]],"normalized":[{"db_name":"MESH","db_id":"D008750"}]},{"id":"8038","type":"Chemical","text":["estrogen"],"offsets":[[822,830]],"normalized":[{"db_name":"MESH","db_id":"D004967"}]},{"id":"8039","type":"Chemical","text":["rilmenidine"],"offsets":[[1207,1218]],"normalized":[{"db_name":"MESH","db_id":"C032302"}]},{"id":"8040","type":"Chemical","text":["alpha-methyldopa"],"offsets":[[1222,1238]],"normalized":[{"db_name":"MESH","db_id":"D008750"}]},{"id":"8041","type":"Disease","text":["hypotension"],"offsets":[[1256,1267]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"8042","type":"Chemical","text":["alpha-methyldopa"],"offsets":[[1402,1418]],"normalized":[{"db_name":"MESH","db_id":"D008750"}]},{"id":"8043","type":"Disease","text":["hypotensive"],"offsets":[[1451,1462]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"8044","type":"Chemical","text":["alpha-methyldopa"],"offsets":[[1475,1491]],"normalized":[{"db_name":"MESH","db_id":"D008750"}]},{"id":"8045","type":"Chemical","text":["rilmenidine"],"offsets":[[1521,1532]],"normalized":[{"db_name":"MESH","db_id":"C032302"}]},{"id":"8046","type":"Disease","text":["hypotension"],"offsets":[[1533,1544]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"8047","type":"Chemical","text":["alpha-methyldopa"],"offsets":[[1559,1575]],"normalized":[{"db_name":"MESH","db_id":"D008750"}]},{"id":"8048","type":"Disease","text":["hypotension"],"offsets":[[1576,1587]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"8049","type":"Disease","text":["a 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{"id":"8126","document_id":"15233872","passages":[{"id":"8127","type":"title","text":["Cardioprotective effect of tincture of Crataegus on isoproterenol-induced myocardial infarction in rats."],"offsets":[[0,104]]},{"id":"8128","type":"abstract","text":["Tincture of Crataegus (TCR), an alcoholic extract of the berries of hawthorn (Crataegus oxycantha), is used in herbal and homeopathic medicine. The present study was done to investigate the protective effect of TCR on experimentally induced myocardial infarction in rats. Pretreatment of TCR, at a dose of 0.5 mL\/100 g bodyweight per day, orally for 30 days, prevented the increase in lipid peroxidation and activity of marker enzymes observed in isoproterenol-induced rats (85 mg kg(-1) s. c. for 2 days at an interval of 24 h). TCR prevented the isoproterenol-induced decrease in antioxidant enzymes in the heart and increased the rate of ADP-stimulated oxygen uptake and respiratory coupling ratio. TCR protected against pathological changes induced by isoproterenol in rat heart. The results show that pretreatment with TCR may be useful in preventing the damage induced by isoproterenol in rat heart."],"offsets":[[105,1010]]}],"entities":[{"id":"8129","type":"Chemical","text":["tincture of Crataegus"],"offsets":[[27,48]],"normalized":[{"db_name":"MESH","db_id":"C007145"}]},{"id":"8130","type":"Chemical","text":["isoproterenol"],"offsets":[[52,65]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"8131","type":"Disease","text":["myocardial infarction"],"offsets":[[74,95]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"8132","type":"Chemical","text":["Tincture of Crataegus"],"offsets":[[105,126]],"normalized":[{"db_name":"MESH","db_id":"C007145"}]},{"id":"8133","type":"Chemical","text":["TCR"],"offsets":[[128,131]],"normalized":[{"db_name":"MESH","db_id":"C007145"}]},{"id":"8134","type":"Chemical","text":["alcoholic extract of the berries of hawthorn"],"offsets":[[137,181]],"normalized":[{"db_name":"MESH","db_id":"C007145"}]},{"id":"8135","type":"Chemical","text":["Crataegus oxycantha"],"offsets":[[183,202]],"normalized":[{"db_name":"MESH","db_id":"C007145"}]},{"id":"8136","type":"Chemical","text":["TCR"],"offsets":[[316,319]],"normalized":[{"db_name":"MESH","db_id":"C007145"}]},{"id":"8137","type":"Disease","text":["myocardial infarction"],"offsets":[[346,367]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"8138","type":"Chemical","text":["TCR"],"offsets":[[393,396]],"normalized":[{"db_name":"MESH","db_id":"C007145"}]},{"id":"8139","type":"Chemical","text":["isoproterenol"],"offsets":[[552,565]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"8140","type":"Chemical","text":["TCR"],"offsets":[[635,638]],"normalized":[{"db_name":"MESH","db_id":"C007145"}]},{"id":"8141","type":"Chemical","text":["isoproterenol"],"offsets":[[653,666]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"8142","type":"Chemical","text":["ADP"],"offsets":[[746,749]],"normalized":[{"db_name":"MESH","db_id":"D000244"}]},{"id":"8143","type":"Chemical","text":["oxygen"],"offsets":[[761,767]],"normalized":[{"db_name":"MESH","db_id":"D010100"}]},{"id":"8144","type":"Chemical","text":["TCR"],"offsets":[[807,810]],"normalized":[{"db_name":"MESH","db_id":"C007145"}]},{"id":"8145","type":"Chemical","text":["isoproterenol"],"offsets":[[861,874]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"8146","type":"Chemical","text":["TCR"],"offsets":[[929,932]],"normalized":[{"db_name":"MESH","db_id":"C007145"}]},{"id":"8147","type":"Chemical","text":["isoproterenol"],"offsets":[[983,996]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]}],"events":[],"coreferences":[],"relations":[{"id":"8148","type":"CID","arg1_id":"8130","arg2_id":"8131","normalized":[]},{"id":"8149","type":"CID","arg1_id":"8130","arg2_id":"8137","normalized":[]},{"id":"8150","type":"CID","arg1_id":"8139","arg2_id":"8131","normalized":[]},{"id":"8151","type":"CID","arg1_id":"8139","arg2_id":"8137","normalized":[]},{"id":"8152","type":"CID","arg1_id":"8141","arg2_id":"8131","normalized":[]},{"id":"8153","type":"CID","arg1_id":"8141","arg2_id":"8137","normalized":[]},{"id":"8154","type":"CID","arg1_id":"8145","arg2_id":"8131","normalized":[]},{"id":"8155","type":"CID","arg1_id":"8145","arg2_id":"8137","normalized":[]},{"id":"8156","type":"CID","arg1_id":"8147","arg2_id":"8131","normalized":[]},{"id":"8157","type":"CID","arg1_id":"8147","arg2_id":"8137","normalized":[]}]}
{"id":"8158","document_id":"15458908","passages":[{"id":"8159","type":"title","text":["Safety and adverse effects associated with raloxifene: multiple outcomes of raloxifene evaluation."],"offsets":[[0,98]]},{"id":"8160","type":"abstract","text":["OBJECTIVE: To examine the effect of raloxifene on major adverse events that occur with postmenopausal estrogen therapy or tamoxifen. METHODS: The Multiple Outcomes of Raloxifene Evaluation, a multicenter, randomized, double-blind trial, enrolled 7,705 postmenopausal women with osteoporosis. Women were randomly assigned to raloxifene 60 mg\/d or 120 mg\/d or placebo. Outcomes included venous thromboembolism, cataracts, gallbladder disease, and endometrial hyperplasia or cancer. RESULTS: During a mean follow-up of 3.3 years, raloxifene was associated with an increased risk for venous thromboembolism (relative risk [RR] 2.1; 95% confidence interval [CI] 1.2-3.8). The excess event rate was 1.8 per 1,000 woman-years (95% CI -0.5-4.1), and the number needed to treat to cause 1 event was 170 (95% CI 100-582) over 3.3 years. Risk in the raloxifene group was higher than in the placebo group for the first 2 years, but decreased to about the same rate as in the placebo group thereafter. Raloxifene did not increase risk for cataracts (RR 0.9; 95% CI 0.8-1.1), gallbladder disease (RR 1.0; 95% CI 0.7-1.3), endometrial hyperplasia (RR 1.3; 95% CI 0.4-5.1), or endometrial cancer (RR 0.9; 95% CI 0.3-2.7). CONCLUSION: Raloxifene was associated with an increased risk for venous thromboembolism, but there was no increased risk for cataracts, gallbladder disease, endometrial hyperplasia, or endometrial cancer. LEVEL OF EVIDENCE: I"],"offsets":[[99,1530]]}],"entities":[{"id":"8161","type":"Chemical","text":["raloxifene"],"offsets":[[43,53]],"normalized":[{"db_name":"MESH","db_id":"D020849"}]},{"id":"8162","type":"Chemical","text":["raloxifene"],"offsets":[[76,86]],"normalized":[{"db_name":"MESH","db_id":"D020849"}]},{"id":"8163","type":"Chemical","text":["raloxifene"],"offsets":[[135,145]],"normalized":[{"db_name":"MESH","db_id":"D020849"}]},{"id":"8164","type":"Chemical","text":["estrogen"],"offsets":[[201,209]],"normalized":[{"db_name":"MESH","db_id":"D004967"}]},{"id":"8165","type":"Chemical","text":["tamoxifen"],"offsets":[[221,230]],"normalized":[{"db_name":"MESH","db_id":"D013629"}]},{"id":"8166","type":"Chemical","text":["Raloxifene"],"offsets":[[266,276]],"normalized":[{"db_name":"MESH","db_id":"D020849"}]},{"id":"8167","type":"Disease","text":["osteoporosis"],"offsets":[[377,389]],"normalized":[{"db_name":"MESH","db_id":"D010024"}]},{"id":"8168","type":"Chemical","text":["raloxifene"],"offsets":[[423,433]],"normalized":[{"db_name":"MESH","db_id":"D020849"}]},{"id":"8169","type":"Disease","text":["venous 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cancer"],"offsets":[[1490,1508]],"normalized":[{"db_name":"MESH","db_id":"D016889"}]}],"events":[],"coreferences":[],"relations":[{"id":"8189","type":"CID","arg1_id":"8161","arg2_id":"8169","normalized":[]},{"id":"8190","type":"CID","arg1_id":"8161","arg2_id":"8176","normalized":[]},{"id":"8191","type":"CID","arg1_id":"8161","arg2_id":"8184","normalized":[]},{"id":"8192","type":"CID","arg1_id":"8162","arg2_id":"8169","normalized":[]},{"id":"8193","type":"CID","arg1_id":"8162","arg2_id":"8176","normalized":[]},{"id":"8194","type":"CID","arg1_id":"8162","arg2_id":"8184","normalized":[]},{"id":"8195","type":"CID","arg1_id":"8163","arg2_id":"8169","normalized":[]},{"id":"8196","type":"CID","arg1_id":"8163","arg2_id":"8176","normalized":[]},{"id":"8197","type":"CID","arg1_id":"8163","arg2_id":"8184","normalized":[]},{"id":"8198","type":"CID","arg1_id":"8166","arg2_id":"8169","normalized":[]},{"id":"8199","type":"CID","arg1_id":"8166","arg2_id":"8176","normalized":[]},{"id":"8200","type":"CID","arg1_id":"8166","arg2_id":"8184","normalized":[]},{"id":"8201","type":"CID","arg1_id":"8168","arg2_id":"8169","normalized":[]},{"id":"8202","type":"CID","arg1_id":"8168","arg2_id":"8176","normalized":[]},{"id":"8203","type":"CID","arg1_id":"8168","arg2_id":"8184","normalized":[]},{"id":"8204","type":"CID","arg1_id":"8175","arg2_id":"8169","normalized":[]},{"id":"8205","type":"CID","arg1_id":"8175","arg2_id":"8176","normalized":[]},{"id":"8206","type":"CID","arg1_id":"8175","arg2_id":"8184","normalized":[]},{"id":"8207","type":"CID","arg1_id":"8177","arg2_id":"8169","normalized":[]},{"id":"8208","type":"CID","arg1_id":"8177","arg2_id":"8176","normalized":[]},{"id":"8209","type":"CID","arg1_id":"8177","arg2_id":"8184","normalized":[]},{"id":"8210","type":"CID","arg1_id":"8178","arg2_id":"8169","normalized":[]},{"id":"8211","type":"CID","arg1_id":"8178","arg2_id":"8176","normalized":[]},{"id":"8212","type":"CID","arg1_id":"8178","arg2_id":"8184","normalized":[]},{"id":"8213","type":"CID","arg1_id":"8183","arg2_id":"8169","normalized":[]},{"id":"8214","type":"CID","arg1_id":"8183","arg2_id":"8176","normalized":[]},{"id":"8215","type":"CID","arg1_id":"8183","arg2_id":"8184","normalized":[]}]}
{"id":"8216","document_id":"15737522","passages":[{"id":"8217","type":"title","text":["Ceftriaxone-associated biliary pseudolithiasis in paediatric surgical patients."],"offsets":[[0,79]]},{"id":"8218","type":"abstract","text":["It is well known that ceftriaxone leads to pseudolithiasis in some patients. Clinical and experimental studies also suggest that situations causing gallbladder dysfunction, such as fasting, may have a role for the development of pseudolithiasis. In this study, we prospectively evaluated the incidence and clinical importance of pseudolithiasis in paediatric surgical patients receiving ceftriaxone treatment, who often had to fast in the post-operative period. Fifty children who were given ceftriaxone were evaluated by serial abdominal sonograms. Of those, 13 (26%) developed biliary pathology. Comparison of the patients with or without pseudolithiasis revealed no significant difference with respect to age, sex, duration of the treatment and starvation variables. After cessation of the treatment, pseudolithiasis resolved spontaneously within a short period. The incidence of pseudolithiasis is not affected by fasting."],"offsets":[[80,1006]]}],"entities":[{"id":"8219","type":"Chemical","text":["Ceftriaxone"],"offsets":[[0,11]],"normalized":[{"db_name":"MESH","db_id":"D002443"}]},{"id":"8220","type":"Disease","text":["biliary pseudolithiasis"],"offsets":[[23,46]],"normalized":[{"db_name":"MESH","db_id":"D001660"}]},{"id":"8221","type":"Chemical","text":["ceftriaxone"],"offsets":[[102,113]],"normalized":[{"db_name":"MESH","db_id":"D002443"}]},{"id":"8222","type":"Disease","text":["pseudolithiasis"],"offsets":[[123,138]],"normalized":[{"db_name":"MESH","db_id":"D001660"}]},{"id":"8223","type":"Disease","text":["gallbladder dysfunction"],"offsets":[[228,251]],"normalized":[{"db_name":"MESH","db_id":"D005705"}]},{"id":"8224","type":"Disease","text":["pseudolithiasis"],"offsets":[[309,324]],"normalized":[{"db_name":"MESH","db_id":"D001660"}]},{"id":"8225","type":"Disease","text":["pseudolithiasis"],"offsets":[[409,424]],"normalized":[{"db_name":"MESH","db_id":"D001660"}]},{"id":"8226","type":"Chemical","text":["ceftriaxone"],"offsets":[[467,478]],"normalized":[{"db_name":"MESH","db_id":"D002443"}]},{"id":"8227","type":"Chemical","text":["ceftriaxone"],"offsets":[[572,583]],"normalized":[{"db_name":"MESH","db_id":"D002443"}]},{"id":"8228","type":"Disease","text":["pseudolithiasis"],"offsets":[[721,736]],"normalized":[{"db_name":"MESH","db_id":"D001660"}]},{"id":"8229","type":"Disease","text":["pseudolithiasis"],"offsets":[[884,899]],"normalized":[{"db_name":"MESH","db_id":"D001660"}]},{"id":"8230","type":"Disease","text":["pseudolithiasis"],"offsets":[[963,978]],"normalized":[{"db_name":"MESH","db_id":"D001660"}]}],"events":[],"coreferences":[],"relations":[{"id":"8231","type":"CID","arg1_id":"8219","arg2_id":"8220","normalized":[]},{"id":"8232","type":"CID","arg1_id":"8219","arg2_id":"8222","normalized":[]},{"id":"8233","type":"CID","arg1_id":"8219","arg2_id":"8224","normalized":[]},{"id":"8234","type":"CID","arg1_id":"8219","arg2_id":"8225","normalized":[]},{"id":"8235","type":"CID","arg1_id":"8219","arg2_id":"8228","normalized":[]},{"id":"8236","type":"CID","arg1_id":"8219","arg2_id":"8229","normalized":[]},{"id":"8237","type":"CID","arg1_id":"8219","arg2_id":"8230","normalized":[]},{"id":"8238","type":"CID","arg1_id":"8221","arg2_id":"8220","normalized":[]},{"id":"8239","type":"CID","arg1_id":"8221","arg2_id":"8222","normalized":[]},{"id":"8240","type":"CID","arg1_id":"8221","arg2_id":"8224","normalized":[]},{"id":"8241","type":"CID","arg1_id":"8221","arg2_id":"8225","normalized":[]},{"id":"8242","type":"CID","arg1_id":"8221","arg2_id":"8228","normalized":[]},{"id":"8243","type":"CID","arg1_id":"8221","arg2_id":"8229","normalized":[]},{"id":"8244","type":"CID","arg1_id":"8221","arg2_id":"8230","normalized":[]},{"id":"8245","type":"CID","arg1_id":"8226","arg2_id":"8220","normalized":[]},{"id":"8246","type":"CID","arg1_id":"8226","arg2_id":"8222","normalized":[]},{"id":"8247","type":"CID","arg1_id":"8226","arg2_id":"8224","normalized":[]},{"id":"8248","type":"CID","arg1_id":"8226","arg2_id":"8225","normalized":[]},{"id":"8249","type":"CID","arg1_id":"8226","arg2_id":"8228","normalized":[]},{"id":"8250","type":"CID","arg1_id":"8226","arg2_id":"8229","normalized":[]},{"id":"8251","type":"CID","arg1_id":"8226","arg2_id":"8230","normalized":[]},{"id":"8252","type":"CID","arg1_id":"8227","arg2_id":"8220","normalized":[]},{"id":"8253","type":"CID","arg1_id":"8227","arg2_id":"8222","normalized":[]},{"id":"8254","type":"CID","arg1_id":"8227","arg2_id":"8224","normalized":[]},{"id":"8255","type":"CID","arg1_id":"8227","arg2_id":"8225","normalized":[]},{"id":"8256","type":"CID","arg1_id":"8227","arg2_id":"8228","normalized":[]},{"id":"8257","type":"CID","arg1_id":"8227","arg2_id":"8229","normalized":[]},{"id":"8258","type":"CID","arg1_id":"8227","arg2_id":"8230","normalized":[]}]}
{"id":"8259","document_id":"16005948","passages":[{"id":"8260","type":"title","text":["Evaluation of the anticocaine monoclonal antibody GNC92H2 as an immunotherapy for cocaine overdose."],"offsets":[[0,99]]},{"id":"8261","type":"abstract","text":["The illicit use of cocaine continues in epidemic proportions and treatment for cocaine overdose remains elusive. Current protein-based technology offers a new therapeutic venue by which antibodies bind the drug in the blood stream, inactivating its toxic effects. The therapeutic potential of the anticocaine antibody GNC92H2 was examined using a model of cocaine overdose. Swiss albino mice prepared with intrajugular catheters were tested in photocell cages after administration of 93 mg\/kg (LD50) of cocaine and GNC92H2 infusions ranging from 30 to 190 mg\/kg. GNC92H2 was delivered 30 min before, concomitantly or 3 min after cocaine treatment. Significant blockade of cocaine toxicity was observed with the higher dose of GNC92H2 (190 mg\/kg), where premorbid behaviors were reduced up to 40%, seizures up to 77% and death by 72%. Importantly, GNC92H2 prevented death even post-cocaine injection. The results support the important potential of GNC92H2 as a therapeutic tool against cocaine overdose."],"offsets":[[100,1102]]}],"entities":[{"id":"8262","type":"Chemical","text":["GNC92H2"],"offsets":[[50,57]],"normalized":[]},{"id":"8263","type":"Disease","text":["cocaine overdose"],"offsets":[[82,98]],"normalized":[{"db_name":"MESH","db_id":"D062787"}]},{"id":"8264","type":"Chemical","text":["cocaine"],"offsets":[[119,126]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"8265","type":"Disease","text":["cocaine overdose"],"offsets":[[179,195]],"normalized":[{"db_name":"MESH","db_id":"D062787"}]},{"id":"8266","type":"Chemical","text":["GNC92H2"],"offsets":[[418,425]],"normalized":[]},{"id":"8267","type":"Disease","text":["cocaine overdose"],"offsets":[[456,472]],"normalized":[{"db_name":"MESH","db_id":"D062787"}]},{"id":"8268","type":"Chemical","text":["cocaine"],"offsets":[[603,610]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"8269","type":"Chemical","text":["GNC92H2"],"offsets":[[615,622]],"normalized":[]},{"id":"8270","type":"Chemical","text":["GNC92H2"],"offsets":[[663,670]],"normalized":[]},{"id":"8271","type":"Chemical","text":["cocaine"],"offsets":[[729,736]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"8272","type":"Chemical","text":["cocaine"],"offsets":[[772,779]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"8273","type":"Disease","text":["toxicity"],"offsets":[[780,788]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"8274","type":"Chemical","text":["GNC92H2"],"offsets":[[826,833]],"normalized":[]},{"id":"8275","type":"Disease","text":["seizures"],"offsets":[[897,905]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"8276","type":"Disease","text":["death"],"offsets":[[920,925]],"normalized":[{"db_name":"MESH","db_id":"D003643"}]},{"id":"8277","type":"Chemical","text":["GNC92H2"],"offsets":[[947,954]],"normalized":[]},{"id":"8278","type":"Disease","text":["death"],"offsets":[[965,970]],"normalized":[{"db_name":"MESH","db_id":"D003643"}]},{"id":"8279","type":"Chemical","text":["cocaine"],"offsets":[[981,988]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"8280","type":"Chemical","text":["GNC92H2"],"offsets":[[1047,1054]],"normalized":[]},{"id":"8281","type":"Disease","text":["cocaine overdose"],"offsets":[[1085,1101]],"normalized":[{"db_name":"MESH","db_id":"D062787"}]}],"events":[],"coreferences":[],"relations":[{"id":"8282","type":"CID","arg1_id":"8264","arg2_id":"8275","normalized":[]},{"id":"8283","type":"CID","arg1_id":"8268","arg2_id":"8275","normalized":[]},{"id":"8284","type":"CID","arg1_id":"8271","arg2_id":"8275","normalized":[]},{"id":"8285","type":"CID","arg1_id":"8272","arg2_id":"8275","normalized":[]},{"id":"8286","type":"CID","arg1_id":"8279","arg2_id":"8275","normalized":[]}]}
{"id":"8287","document_id":"16167916","passages":[{"id":"8288","type":"title","text":["The effects of short-term raloxifene therapy on fibrinolysis markers: TAFI, tPA, and PAI-1."],"offsets":[[0,91]]},{"id":"8289","type":"abstract","text":["BACKGROUND: Markers of fibrinolysis, thrombin-activatable fibrinolysis inhibitor (TAFI), tissue-type plasminogen activator (tPA), and plasminogen activator inhibitor-1 (PAI-1) levels were studied for the evaluation of short-term effects of raloxifene administration in postmenopausal women. METHODS: Thirty-nine postmenopausal women with osteopenia or osteoporosis were included in this prospective, controlled clinical study. Twenty-five women were given raloxifene hydrochloride (60 mg\/day) plus calcium (500 mg\/day). Age-matched controls (n = 14) were given only calcium. Plasma TAFI, tPA, and PAI-1 antigen levels were measured at baseline and after 3 months of treatment by commercially available ELISA kits. Variations of individuals were assessed by Wilcoxon's test. Relationship between those markers and demographic characteristics were investigated. RESULTS: Three months of raloxifene treatment was associated with a significant decrease in the plasma TAFI antigen concentrations (16% change, P < 0.01), and a significant increase in tPA antigen concentrations (25% change, P < 0.05). A significant correlation was found between baseline TAFI antigen concentrations and the duration of amenorrhea (P < 0.05; r = 0.33). CONCLUSION: We suggest that the increased risk of venous thromboembolism due to raloxifene treatment may be related to increased tPA levels, but not TAFI levels."],"offsets":[[92,1483]]}],"entities":[{"id":"8290","type":"Chemical","text":["raloxifene"],"offsets":[[26,36]],"normalized":[{"db_name":"MESH","db_id":"D020849"}]},{"id":"8291","type":"Chemical","text":["raloxifene"],"offsets":[[332,342]],"normalized":[{"db_name":"MESH","db_id":"D020849"}]},{"id":"8292","type":"Disease","text":["osteopenia"],"offsets":[[430,440]],"normalized":[{"db_name":"MESH","db_id":"D001851"}]},{"id":"8293","type":"Disease","text":["osteoporosis"],"offsets":[[444,456]],"normalized":[{"db_name":"MESH","db_id":"D010024"}]},{"id":"8294","type":"Chemical","text":["raloxifene hydrochloride"],"offsets":[[548,572]],"normalized":[{"db_name":"MESH","db_id":"D020849"}]},{"id":"8295","type":"Chemical","text":["calcium"],"offsets":[[590,597]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"8296","type":"Chemical","text":["calcium"],"offsets":[[658,665]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"8297","type":"Chemical","text":["raloxifene"],"offsets":[[977,987]],"normalized":[{"db_name":"MESH","db_id":"D020849"}]},{"id":"8298","type":"Disease","text":["amenorrhea"],"offsets":[[1289,1299]],"normalized":[{"db_name":"MESH","db_id":"D000568"}]},{"id":"8299","type":"Disease","text":["venous thromboembolism"],"offsets":[[1372,1394]],"normalized":[{"db_name":"MESH","db_id":"D054556"}]},{"id":"8300","type":"Chemical","text":["raloxifene"],"offsets":[[1402,1412]],"normalized":[{"db_name":"MESH","db_id":"D020849"}]}],"events":[],"coreferences":[],"relations":[{"id":"8301","type":"CID","arg1_id":"8290","arg2_id":"8299","normalized":[]},{"id":"8302","type":"CID","arg1_id":"8291","arg2_id":"8299","normalized":[]},{"id":"8303","type":"CID","arg1_id":"8294","arg2_id":"8299","normalized":[]},{"id":"8304","type":"CID","arg1_id":"8297","arg2_id":"8299","normalized":[]},{"id":"8305","type":"CID","arg1_id":"8300","arg2_id":"8299","normalized":[]}]}
{"id":"8306","document_id":"16403073","passages":[{"id":"8307","type":"title","text":["Ketoconazole induced torsades de pointes without concomitant use of QT interval-prolonging drug."],"offsets":[[0,96]]},{"id":"8308","type":"abstract","text":["Ketoconazole is not known to be proarrhythmic without concomitant use of QT interval-prolonging drugs. We report a woman with coronary artery disease who developed a markedly prolonged QT interval and torsades de pointes (TdP) after taking ketoconazole for treatment of fungal infection. Her QT interval returned to normal upon withdrawal of ketoconazole. Genetic study did not find any mutation in her genes that encode cardiac IKr channel proteins. We postulate that by virtue of its direct blocking action on IKr, ketoconazole alone may prolong QT interval and induce TdP. This calls for attention when ketoconazole is administered to patients with risk factors for acquired long QT syndrome."],"offsets":[[97,792]]}],"entities":[{"id":"8309","type":"Chemical","text":["Ketoconazole"],"offsets":[[0,12]],"normalized":[{"db_name":"MESH","db_id":"D007654"}]},{"id":"8310","type":"Disease","text":["torsades de pointes"],"offsets":[[21,40]],"normalized":[{"db_name":"MESH","db_id":"D016171"}]},{"id":"8311","type":"Chemical","text":["Ketoconazole"],"offsets":[[97,109]],"normalized":[{"db_name":"MESH","db_id":"D007654"}]},{"id":"8312","type":"Disease","text":["coronary artery disease"],"offsets":[[223,246]],"normalized":[{"db_name":"MESH","db_id":"D003324"}]},{"id":"8313","type":"Disease","text":["prolonged QT interval"],"offsets":[[272,293]],"normalized":[{"db_name":"MESH","db_id":"D008133"}]},{"id":"8314","type":"Disease","text":["torsades de pointes"],"offsets":[[298,317]],"normalized":[{"db_name":"MESH","db_id":"D016171"}]},{"id":"8315","type":"Disease","text":["TdP"],"offsets":[[319,322]],"normalized":[{"db_name":"MESH","db_id":"D016171"}]},{"id":"8316","type":"Chemical","text":["ketoconazole"],"offsets":[[337,349]],"normalized":[{"db_name":"MESH","db_id":"D007654"}]},{"id":"8317","type":"Disease","text":["fungal infection"],"offsets":[[367,383]],"normalized":[{"db_name":"MESH","db_id":"D009181"}]},{"id":"8318","type":"Chemical","text":["ketoconazole"],"offsets":[[439,451]],"normalized":[{"db_name":"MESH","db_id":"D007654"}]},{"id":"8319","type":"Chemical","text":["ketoconazole"],"offsets":[[614,626]],"normalized":[{"db_name":"MESH","db_id":"D007654"}]},{"id":"8320","type":"Disease","text":["TdP"],"offsets":[[668,671]],"normalized":[{"db_name":"MESH","db_id":"D016171"}]},{"id":"8321","type":"Chemical","text":["ketoconazole"],"offsets":[[703,715]],"normalized":[{"db_name":"MESH","db_id":"D007654"}]},{"id":"8322","type":"Disease","text":["long QT syndrome"],"offsets":[[775,791]],"normalized":[{"db_name":"MESH","db_id":"D008133"}]}],"events":[],"coreferences":[],"relations":[{"id":"8323","type":"CID","arg1_id":"8309","arg2_id":"8310","normalized":[]},{"id":"8324","type":"CID","arg1_id":"8309","arg2_id":"8314","normalized":[]},{"id":"8325","type":"CID","arg1_id":"8309","arg2_id":"8315","normalized":[]},{"id":"8326","type":"CID","arg1_id":"8309","arg2_id":"8320","normalized":[]},{"id":"8327","type":"CID","arg1_id":"8311","arg2_id":"8310","normalized":[]},{"id":"8328","type":"CID","arg1_id":"8311","arg2_id":"8314","normalized":[]},{"id":"8329","type":"CID","arg1_id":"8311","arg2_id":"8315","normalized":[]},{"id":"8330","type":"CID","arg1_id":"8311","arg2_id":"8320","normalized":[]},{"id":"8331","type":"CID","arg1_id":"8316","arg2_id":"8310","normalized":[]},{"id":"8332","type":"CID","arg1_id":"8316","arg2_id":"8314","normalized":[]},{"id":"8333","type":"CID","arg1_id":"8316","arg2_id":"8315","normalized":[]},{"id":"8334","type":"CID","arg1_id":"8316","arg2_id":"8320","normalized":[]},{"id":"8335","type":"CID","arg1_id":"8318","arg2_id":"8310","normalized":[]},{"id":"8336","type":"CID","arg1_id":"8318","arg2_id":"8314","normalized":[]},{"id":"8337","type":"CID","arg1_id":"8318","arg2_id":"8315","normalized":[]},{"id":"8338","type":"CID","arg1_id":"8318","arg2_id":"8320","normalized":[]},{"id":"8339","type":"CID","arg1_id":"8319","arg2_id":"8310","normalized":[]},{"id":"8340","type":"CID","arg1_id":"8319","arg2_id":"8314","normalized":[]},{"id":"8341","type":"CID","arg1_id":"8319","arg2_id":"8315","normalized":[]},{"id":"8342","type":"CID","arg1_id":"8319","arg2_id":"8320","normalized":[]},{"id":"8343","type":"CID","arg1_id":"8321","arg2_id":"8310","normalized":[]},{"id":"8344","type":"CID","arg1_id":"8321","arg2_id":"8314","normalized":[]},{"id":"8345","type":"CID","arg1_id":"8321","arg2_id":"8315","normalized":[]},{"id":"8346","type":"CID","arg1_id":"8321","arg2_id":"8320","normalized":[]},{"id":"8347","type":"CID","arg1_id":"8309","arg2_id":"8313","normalized":[]},{"id":"8348","type":"CID","arg1_id":"8309","arg2_id":"8322","normalized":[]},{"id":"8349","type":"CID","arg1_id":"8311","arg2_id":"8313","normalized":[]},{"id":"8350","type":"CID","arg1_id":"8311","arg2_id":"8322","normalized":[]},{"id":"8351","type":"CID","arg1_id":"8316","arg2_id":"8313","normalized":[]},{"id":"8352","type":"CID","arg1_id":"8316","arg2_id":"8322","normalized":[]},{"id":"8353","type":"CID","arg1_id":"8318","arg2_id":"8313","normalized":[]},{"id":"8354","type":"CID","arg1_id":"8318","arg2_id":"8322","normalized":[]},{"id":"8355","type":"CID","arg1_id":"8319","arg2_id":"8313","normalized":[]},{"id":"8356","type":"CID","arg1_id":"8319","arg2_id":"8322","normalized":[]},{"id":"8357","type":"CID","arg1_id":"8321","arg2_id":"8313","normalized":[]},{"id":"8358","type":"CID","arg1_id":"8321","arg2_id":"8322","normalized":[]}]}
{"id":"8359","document_id":"16755009","passages":[{"id":"8360","type":"title","text":["Pharmacological evidence for the potential of Daucus carota in the management of cognitive dysfunctions."],"offsets":[[0,104]]},{"id":"8361","type":"abstract","text":["The present study was aimed at investigating the effects of Daucus carota seeds on cognitive functions, total serum cholesterol levels and brain cholinesterase activity in mice. The ethanolic extract of Daucus carota seeds (DCE) was administered orally in three doses (100, 200, 400 mg\/kg) for seven successive days to different groups of young and aged mice. Elevated plus maze and passive avoidance apparatus served as the exteroceptive behavioral models for testing memory. Diazepam-, scopolamine- and ageing-induced amnesia served as the interoceptive behavioral models. DCE (200, 400 mg\/kg, p.o.) showed significant improvement in memory scores of young and aged mice. The extent of memory improvement evoked by DCE was 23% at the dose of 200 mg\/kg and 35% at the dose of 400 mg\/kg in young mice using elevated plus maze. Similarly, significant improvements in memory scores were observed using passive avoidance apparatus and aged mice. Furthermore, DCE reversed the amnesia induced by scopolamine (0.4 mg\/kg, i.p.) and diazepam (1 mg\/kg, i.p.). Daucus carota extract (200, 400 mg\/kg, p.o.) reduced significantly the brain acetylcholinesterase activity and cholesterol levels in young and aged mice. The extent of inhibition of brain cholinesterase activity evoked by DCE at the dose of 400 mg\/kg was 22% in young and 19% in aged mice. There was a remarkable reduction in total cholesterol level as well, to the extent of 23% in young and 21% in aged animals with this dose of DCE. Therefore, DCE may prove to be a useful remedy for the management of cognitive dysfunctions on account of its multifarious beneficial effects such as, memory improving property, cholesterol lowering property and anticholinesterase activity."],"offsets":[[105,1833]]}],"entities":[{"id":"8362","type":"Disease","text":["cognitive dysfunctions"],"offsets":[[81,103]],"normalized":[{"db_name":"MESH","db_id":"D003072"}]},{"id":"8363","type":"Chemical","text":["cholesterol"],"offsets":[[221,232]],"normalized":[{"db_name":"MESH","db_id":"D002784"}]},{"id":"8364","type":"Chemical","text":["extract of Daucus carota seeds"],"offsets":[[297,327]],"normalized":[{"db_name":"MESH","db_id":"D010936"}]},{"id":"8365","type":"Chemical","text":["DCE"],"offsets":[[329,332]],"normalized":[{"db_name":"MESH","db_id":"D010936"}]},{"id":"8366","type":"Chemical","text":["Diazepam"],"offsets":[[582,590]],"normalized":[{"db_name":"MESH","db_id":"D003975"}]},{"id":"8367","type":"Chemical","text":["scopolamine"],"offsets":[[593,604]],"normalized":[{"db_name":"MESH","db_id":"D012601"}]},{"id":"8368","type":"Disease","text":["amnesia"],"offsets":[[625,632]],"normalized":[{"db_name":"MESH","db_id":"D000647"}]},{"id":"8369","type":"Chemical","text":["DCE"],"offsets":[[680,683]],"normalized":[{"db_name":"MESH","db_id":"D010936"}]},{"id":"8370","type":"Chemical","text":["DCE"],"offsets":[[822,825]],"normalized":[{"db_name":"MESH","db_id":"D010936"}]},{"id":"8371","type":"Chemical","text":["DCE"],"offsets":[[1061,1064]],"normalized":[{"db_name":"MESH","db_id":"D010936"}]},{"id":"8372","type":"Disease","text":["amnesia"],"offsets":[[1078,1085]],"normalized":[{"db_name":"MESH","db_id":"D000647"}]},{"id":"8373","type":"Chemical","text":["scopolamine"],"offsets":[[1097,1108]],"normalized":[{"db_name":"MESH","db_id":"D012601"}]},{"id":"8374","type":"Chemical","text":["diazepam"],"offsets":[[1131,1139]],"normalized":[{"db_name":"MESH","db_id":"D003975"}]},{"id":"8375","type":"Chemical","text":["Daucus carota extract"],"offsets":[[1157,1178]],"normalized":[{"db_name":"MESH","db_id":"D010936"}]},{"id":"8376","type":"Chemical","text":["cholesterol"],"offsets":[[1268,1279]],"normalized":[{"db_name":"MESH","db_id":"D002784"}]},{"id":"8377","type":"Chemical","text":["DCE"],"offsets":[[1379,1382]],"normalized":[{"db_name":"MESH","db_id":"D010936"}]},{"id":"8378","type":"Chemical","text":["cholesterol"],"offsets":[[1489,1500]],"normalized":[{"db_name":"MESH","db_id":"D002784"}]},{"id":"8379","type":"Chemical","text":["DCE"],"offsets":[[1588,1591]],"normalized":[{"db_name":"MESH","db_id":"D010936"}]},{"id":"8380","type":"Chemical","text":["DCE"],"offsets":[[1604,1607]],"normalized":[{"db_name":"MESH","db_id":"D010936"}]},{"id":"8381","type":"Disease","text":["cognitive dysfunctions"],"offsets":[[1662,1684]],"normalized":[{"db_name":"MESH","db_id":"D003072"}]},{"id":"8382","type":"Chemical","text":["cholesterol"],"offsets":[[1771,1782]],"normalized":[{"db_name":"MESH","db_id":"D002784"}]}],"events":[],"coreferences":[],"relations":[{"id":"8383","type":"CID","arg1_id":"8366","arg2_id":"8368","normalized":[]},{"id":"8384","type":"CID","arg1_id":"8366","arg2_id":"8372","normalized":[]},{"id":"8385","type":"CID","arg1_id":"8374","arg2_id":"8368","normalized":[]},{"id":"8386","type":"CID","arg1_id":"8374","arg2_id":"8372","normalized":[]},{"id":"8387","type":"CID","arg1_id":"8367","arg2_id":"8368","normalized":[]},{"id":"8388","type":"CID","arg1_id":"8367","arg2_id":"8372","normalized":[]},{"id":"8389","type":"CID","arg1_id":"8373","arg2_id":"8368","normalized":[]},{"id":"8390","type":"CID","arg1_id":"8373","arg2_id":"8372","normalized":[]}]}
{"id":"8391","document_id":"16904497","passages":[{"id":"8392","type":"title","text":["Cauda equina syndrome after epidural steroid injection: a case report."],"offsets":[[0,70]]},{"id":"8393","type":"abstract","text":["OBJECTIVE: Conventional treatment methods of lumbusacral radiculopathy are physical therapy, epidural steroid injections, oral medications, and spinal manipulative therapy. Cauda equina syndrome is a rare complication of epidural anesthesia. The following case is a report of cauda equina syndrome possibly caused by epidural injection of triamcinolone and bupivacaine. CLINICAL FEATURES: A 50-year-old woman with low back and right leg pain was scheduled for epidural steroid injection. INTERVENTION AND OUTCOME: An 18-gauge Touhy needle was inserted until loss of resistance occurred at the L4-5 level. Spread of the contrast medium within the epidural space was determined by radiographic imaging. After verifying the epidural space, bupivacaine and triamcinolone diacetate were injected. After the injection, there was a reduction in radicular symptoms. Three hours later, she complained of perineal numbness and lower extremity weakness. The neurologic evaluation revealed loss of sensation in the saddle area and medial aspect of her right leg. There was a decrease in the perception of pinprick test. Deep-tendon reflexes were decreased especially in the right leg. She was unable to urinate. The patient's symptoms improved slightly over the next few hours. She had a gradual return of motor function and ability of feeling Foley catheter. All of the symptoms were completely resolved over the next 8 hours. CONCLUSION: Complications associated with epidural steroid injections are rare. Clinical examination and continued vigilance for neurologic deterioration after epidural steroid injections is important."],"offsets":[[71,1688]]}],"entities":[{"id":"8394","type":"Disease","text":["Cauda equina syndrome"],"offsets":[[0,21]],"normalized":[{"db_name":"MESH","db_id":"D011128"}]},{"id":"8395","type":"Chemical","text":["steroid"],"offsets":[[37,44]],"normalized":[{"db_name":"MESH","db_id":"D013256"}]},{"id":"8396","type":"Disease","text":["radiculopathy"],"offsets":[[128,141]],"normalized":[{"db_name":"MESH","db_id":"D011843"}]},{"id":"8397","type":"Chemical","text":["steroid"],"offsets":[[173,180]],"normalized":[{"db_name":"MESH","db_id":"D013256"}]},{"id":"8398","type":"Disease","text":["Cauda equina syndrome"],"offsets":[[244,265]],"normalized":[{"db_name":"MESH","db_id":"D011128"}]},{"id":"8399","type":"Disease","text":["cauda equina syndrome"],"offsets":[[347,368]],"normalized":[{"db_name":"MESH","db_id":"D011128"}]},{"id":"8400","type":"Chemical","text":["triamcinolone"],"offsets":[[410,423]],"normalized":[{"db_name":"MESH","db_id":"D014221"}]},{"id":"8401","type":"Chemical","text":["bupivacaine"],"offsets":[[428,439]],"normalized":[{"db_name":"MESH","db_id":"D002045"}]},{"id":"8402","type":"Disease","text":["low back and right leg pain"],"offsets":[[485,512]],"normalized":[{"db_name":"MESH","db_id":"D017116"},{"db_name":"MESH","db_id":"D010146"}]},{"id":"8403","type":"Disease","text":["low back","pain"],"offsets":[[485,493],[508,512]],"normalized":[{"db_name":"MESH","db_id":"D017116"}]},{"id":"8404","type":"Disease","text":["pain"],"offsets":[[508,512]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"8405","type":"Chemical","text":["steroid"],"offsets":[[540,547]],"normalized":[{"db_name":"MESH","db_id":"D013256"}]},{"id":"8406","type":"Chemical","text":["bupivacaine"],"offsets":[[808,819]],"normalized":[{"db_name":"MESH","db_id":"D002045"}]},{"id":"8407","type":"Chemical","text":["triamcinolone diacetate"],"offsets":[[824,847]],"normalized":[{"db_name":"MESH","db_id":"C030262"}]},{"id":"8408","type":"Disease","text":["numbness"],"offsets":[[975,983]],"normalized":[{"db_name":"MESH","db_id":"D006987"}]},{"id":"8409","type":"Disease","text":["lower extremity weakness"],"offsets":[[988,1012]],"normalized":[{"db_name":"MESH","db_id":"D020335"}]},{"id":"8410","type":"Disease","text":["loss of sensation"],"offsets":[[1049,1066]],"normalized":[{"db_name":"MESH","db_id":"D006987"}]},{"id":"8411","type":"Chemical","text":["steroid"],"offsets":[[1538,1545]],"normalized":[{"db_name":"MESH","db_id":"D013256"}]},{"id":"8412","type":"Disease","text":["neurologic deterioration"],"offsets":[[1616,1640]],"normalized":[{"db_name":"MESH","db_id":"D009422"}]},{"id":"8413","type":"Chemical","text":["steroid"],"offsets":[[1656,1663]],"normalized":[{"db_name":"MESH","db_id":"D013256"}]}],"events":[],"coreferences":[],"relations":[{"id":"8414","type":"CID","arg1_id":"8407","arg2_id":"8394","normalized":[]},{"id":"8415","type":"CID","arg1_id":"8407","arg2_id":"8398","normalized":[]},{"id":"8416","type":"CID","arg1_id":"8407","arg2_id":"8399","normalized":[]},{"id":"8417","type":"CID","arg1_id":"8401","arg2_id":"8394","normalized":[]},{"id":"8418","type":"CID","arg1_id":"8401","arg2_id":"8398","normalized":[]},{"id":"8419","type":"CID","arg1_id":"8401","arg2_id":"8399","normalized":[]},{"id":"8420","type":"CID","arg1_id":"8406","arg2_id":"8394","normalized":[]},{"id":"8421","type":"CID","arg1_id":"8406","arg2_id":"8398","normalized":[]},{"id":"8422","type":"CID","arg1_id":"8406","arg2_id":"8399","normalized":[]}]}
{"id":"8423","document_id":"16938416","passages":[{"id":"8424","type":"title","text":["High-dose testosterone is associated with atherosclerosis in postmenopausal women."],"offsets":[[0,82]]},{"id":"8425","type":"abstract","text":["OBJECTIVES: To study the long-term effects of androgen treatment on atherosclerosis in postmenopausal women. METHODS: In a population-based study in 513 naturally postmenopausal women aged 54-67 years, we studied the association between self-reported intramuscularly administered high-dose estrogen-testosterone therapy (estradiol- and testosterone esters) and aortic atherosclerosis. Aortic atherosclerosis was diagnosed by radiographic detection of calcified deposits in the abdominal aorta, which have been shown to reflect intima atherosclerosis. Hormone therapy users were compared with never users. RESULTS: Intramuscular hormone therapy use for 1 year or longer was reported by 25 women. In almost half of these women severe atherosclerosis of the aorta was present (n=11), while in women without hormone use severe atherosclerosis of the aorta was present in less than 20% (OR 3.1; 95% CI, 1.1-8.5, adjusted for age, years since menopause, smoking, and body mass index). The association remained after additional adjustment for diabetes, cholesterol level, systolic blood pressure, or alcohol use. No association was found for hormone use less than 1 year. CONCLUSION: Our results suggest that high-dose testosterone therapy may adversely affect atherosclerosis in postmenopausal women and indicate that androgen replacement in these women may not be harmless."],"offsets":[[83,1451]]}],"entities":[{"id":"8426","type":"Chemical","text":["testosterone"],"offsets":[[10,22]],"normalized":[{"db_name":"MESH","db_id":"D013739"}]},{"id":"8427","type":"Disease","text":["atherosclerosis"],"offsets":[[42,57]],"normalized":[{"db_name":"MESH","db_id":"D050197"}]},{"id":"8428","type":"Disease","text":["atherosclerosis"],"offsets":[[151,166]],"normalized":[{"db_name":"MESH","db_id":"D050197"}]},{"id":"8429","type":"Chemical","text":["estrogen"],"offsets":[[373,381]],"normalized":[{"db_name":"MESH","db_id":"D004967"}]},{"id":"8430","type":"Chemical","text":["testosterone"],"offsets":[[382,394]],"normalized":[{"db_name":"MESH","db_id":"D013739"}]},{"id":"8431","type":"Chemical","text":["estradiol- and testosterone esters"],"offsets":[[404,438]],"normalized":[{"db_name":"MESH","db_id":"C032109"}]},{"id":"8432","type":"Disease","text":["atherosclerosis"],"offsets":[[451,466]],"normalized":[{"db_name":"MESH","db_id":"D050197"}]},{"id":"8433","type":"Disease","text":["atherosclerosis"],"offsets":[[475,490]],"normalized":[{"db_name":"MESH","db_id":"D050197"}]},{"id":"8434","type":"Disease","text":["atherosclerosis"],"offsets":[[617,632]],"normalized":[{"db_name":"MESH","db_id":"D050197"}]},{"id":"8435","type":"Disease","text":["atherosclerosis"],"offsets":[[815,830]],"normalized":[{"db_name":"MESH","db_id":"D050197"}]},{"id":"8436","type":"Disease","text":["atherosclerosis"],"offsets":[[906,921]],"normalized":[{"db_name":"MESH","db_id":"D050197"}]},{"id":"8437","type":"Disease","text":["diabetes"],"offsets":[[1119,1127]],"normalized":[{"db_name":"MESH","db_id":"D003920"}]},{"id":"8438","type":"Chemical","text":["cholesterol"],"offsets":[[1129,1140]],"normalized":[{"db_name":"MESH","db_id":"D002784"}]},{"id":"8439","type":"Chemical","text":["alcohol"],"offsets":[[1176,1183]],"normalized":[{"db_name":"MESH","db_id":"D000431"}]},{"id":"8440","type":"Chemical","text":["testosterone"],"offsets":[[1295,1307]],"normalized":[{"db_name":"MESH","db_id":"D013739"}]},{"id":"8441","type":"Disease","text":["atherosclerosis"],"offsets":[[1337,1352]],"normalized":[{"db_name":"MESH","db_id":"D050197"}]}],"events":[],"coreferences":[],"relations":[{"id":"8442","type":"CID","arg1_id":"8426","arg2_id":"8427","normalized":[]},{"id":"8443","type":"CID","arg1_id":"8426","arg2_id":"8428","normalized":[]},{"id":"8444","type":"CID","arg1_id":"8426","arg2_id":"8432","normalized":[]},{"id":"8445","type":"CID","arg1_id":"8426","arg2_id":"8433","normalized":[]},{"id":"8446","type":"CID","arg1_id":"8426","arg2_id":"8434","normalized":[]},{"id":"8447","type":"CID","arg1_id":"8426","arg2_id":"8435","normalized":[]},{"id":"8448","type":"CID","arg1_id":"8426","arg2_id":"8436","normalized":[]},{"id":"8449","type":"CID","arg1_id":"8426","arg2_id":"8441","normalized":[]},{"id":"8450","type":"CID","arg1_id":"8430","arg2_id":"8427","normalized":[]},{"id":"8451","type":"CID","arg1_id":"8430","arg2_id":"8428","normalized":[]},{"id":"8452","type":"CID","arg1_id":"8430","arg2_id":"8432","normalized":[]},{"id":"8453","type":"CID","arg1_id":"8430","arg2_id":"8433","normalized":[]},{"id":"8454","type":"CID","arg1_id":"8430","arg2_id":"8434","normalized":[]},{"id":"8455","type":"CID","arg1_id":"8430","arg2_id":"8435","normalized":[]},{"id":"8456","type":"CID","arg1_id":"8430","arg2_id":"8436","normalized":[]},{"id":"8457","type":"CID","arg1_id":"8430","arg2_id":"8441","normalized":[]},{"id":"8458","type":"CID","arg1_id":"8440","arg2_id":"8427","normalized":[]},{"id":"8459","type":"CID","arg1_id":"8440","arg2_id":"8428","normalized":[]},{"id":"8460","type":"CID","arg1_id":"8440","arg2_id":"8432","normalized":[]},{"id":"8461","type":"CID","arg1_id":"8440","arg2_id":"8433","normalized":[]},{"id":"8462","type":"CID","arg1_id":"8440","arg2_id":"8434","normalized":[]},{"id":"8463","type":"CID","arg1_id":"8440","arg2_id":"8435","normalized":[]},{"id":"8464","type":"CID","arg1_id":"8440","arg2_id":"8436","normalized":[]},{"id":"8465","type":"CID","arg1_id":"8440","arg2_id":"8441","normalized":[]}]}
{"id":"8466","document_id":"17147461","passages":[{"id":"8467","type":"title","text":["Sirolimus-associated proteinuria and renal dysfunction."],"offsets":[[0,55]]},{"id":"8468","type":"abstract","text":["Sirolimus is a novel immunosuppressant with potent antiproliferative actions through its ability to inhibit the raptor-containing mammalian target of rapamycin protein kinase. Sirolimus represents a major therapeutic advance in the prevention of acute renal allograft rejection and chronic allograft nephropathy. Its role in the therapy of glomerulonephritis, autoimmunity, cystic renal diseases and renal cancer is under investigation. Because sirolimus does not share the vasomotor renal adverse effects exhibited by calcineurin inhibitors, it has been designated a 'non-nephrotoxic drug'. However, clinical reports suggest that, under some circumstances, sirolimus is associated with proteinuria and acute renal dysfunction. A common risk factor appears to be presence of pre-existing chronic renal damage. The mechanisms of sirolimus-associated proteinuria are multifactorial and may be due to an increase in glomerular capillary pressure following calcineurin inhibitor withdrawal. It has also been suggested that sirolimus directly causes increased glomerular permeability\/injury, but evidence for this mechanism is currently inconclusive. The acute renal dysfunction associated with sirolimus (such as in delayed graft function) may be due to suppression of compensatory renal cell proliferation and survival\/repair processes. Although these adverse effects occur in some patients, their occurrence could be minimised by knowledge of the molecular effects of sirolimus on the kidney, the use of sirolimus in appropriate patient populations, close monitoring of proteinuria and renal function, use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers if proteinuria occurs and withdrawal if needed. Further long-term analysis of renal allograft studies using sirolimus as de novo immunosuppression along with clinical and laboratory studies will refine these issues in the future."],"offsets":[[56,1969]]}],"entities":[{"id":"8469","type":"Chemical","text":["Sirolimus"],"offsets":[[0,9]],"normalized":[{"db_name":"MESH","db_id":"D020123"}]},{"id":"8470","type":"Disease","text":["proteinuria"],"offsets":[[21,32]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]},{"id":"8471","type":"Disease","text":["renal dysfunction"],"offsets":[[37,54]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"8472","type":"Chemical","text":["Sirolimus"],"offsets":[[56,65]],"normalized":[{"db_name":"MESH","db_id":"D020123"}]},{"id":"8473","type":"Chemical","text":["rapamycin"],"offsets":[[206,215]],"normalized":[{"db_name":"MESH","db_id":"D020123"}]},{"id":"8474","type":"Chemical","text":["Sirolimus"],"offsets":[[232,241]],"normalized":[{"db_name":"MESH","db_id":"D020123"}]},{"id":"8475","type":"Disease","text":["nephropathy"],"offsets":[[356,367]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"8476","type":"Disease","text":["glomerulonephritis"],"offsets":[[396,414]],"normalized":[{"db_name":"MESH","db_id":"D005921"}]},{"id":"8477","type":"Disease","text":["autoimmunity"],"offsets":[[416,428]],"normalized":[{"db_name":"MESH","db_id":"D001327"}]},{"id":"8478","type":"Disease","text":["cystic renal diseases"],"offsets":[[430,451]],"normalized":[{"db_name":"MESH","db_id":"D052177"}]},{"id":"8479","type":"Disease","text":["renal cancer"],"offsets":[[456,468]],"normalized":[{"db_name":"MESH","db_id":"D007680"}]},{"id":"8480","type":"Chemical","text":["sirolimus"],"offsets":[[501,510]],"normalized":[{"db_name":"MESH","db_id":"D020123"}]},{"id":"8481","type":"Disease","text":["nephrotoxic"],"offsets":[[629,640]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"8482","type":"Chemical","text":["sirolimus"],"offsets":[[714,723]],"normalized":[{"db_name":"MESH","db_id":"D020123"}]},{"id":"8483","type":"Disease","text":["proteinuria"],"offsets":[[743,754]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]},{"id":"8484","type":"Disease","text":["acute renal dysfunction"],"offsets":[[759,782]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"8485","type":"Disease","text":["chronic renal 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{"id":"8594","document_id":"17241784","passages":[{"id":"8595","type":"title","text":["Progressive myopathy with up-regulation of MHC-I associated with statin therapy."],"offsets":[[0,80]]},{"id":"8596","type":"abstract","text":["Statins can cause a necrotizing myopathy and hyperCKaemia which is reversible on cessation of the drug. What is less well known is a phenomenon whereby statins may induce a myopathy, which persists or may progress after stopping the drug. We investigated the muscle pathology in 8 such cases. All had myofibre necrosis but only 3 had an inflammatory infiltrate. In all cases there was diffuse or multifocal up-regulation of MHC-I expression even in non-necrotic fibres. Progressive improvement occurred in 7 cases after commencement of prednisolone and methotrexate, and in one case spontaneously. These observations suggest that statins may initiate an immune-mediated myopathy that persists after withdrawal of the drug and responds to immunosuppressive therapy. The mechanism of this myopathy is uncertain but may involve the induction by statins of an endoplasmic reticulum stress response with associated up-regulation of MHC-I expression and antigen presentation by muscle fibres."],"offsets":[[81,1067]]}],"entities":[{"id":"8597","type":"Disease","text":["myopathy"],"offsets":[[12,20]],"normalized":[{"db_name":"MESH","db_id":"D009135"}]},{"id":"8598","type":"Chemical","text":["statin"],"offsets":[[65,71]],"normalized":[{"db_name":"MESH","db_id":"D019821"}]},{"id":"8599","type":"Chemical","text":["Statins"],"offsets":[[81,88]],"normalized":[{"db_name":"MESH","db_id":"D019821"}]},{"id":"8600","type":"Disease","text":["myopathy"],"offsets":[[113,121]],"normalized":[{"db_name":"MESH","db_id":"D009135"}]},{"id":"8601","type":"Disease","text":["hyperCKaemia"],"offsets":[[126,138]],"normalized":[]},{"id":"8602","type":"Chemical","text":["statins"],"offsets":[[233,240]],"normalized":[{"db_name":"MESH","db_id":"D019821"}]},{"id":"8603","type":"Disease","text":["myopathy"],"offsets":[[254,262]],"normalized":[{"db_name":"MESH","db_id":"D009135"}]},{"id":"8604","type":"Disease","text":["necrosis"],"offsets":[[391,399]],"normalized":[{"db_name":"MESH","db_id":"D009336"}]},{"id":"8605","type":"Disease","text":["necrotic"],"offsets":[[534,542]],"normalized":[{"db_name":"MESH","db_id":"D009336"}]},{"id":"8606","type":"Chemical","text":["prednisolone"],"offsets":[[617,629]],"normalized":[{"db_name":"MESH","db_id":"D011239"}]},{"id":"8607","type":"Chemical","text":["methotrexate"],"offsets":[[634,646]],"normalized":[{"db_name":"MESH","db_id":"D008727"}]},{"id":"8608","type":"Chemical","text":["statins"],"offsets":[[711,718]],"normalized":[{"db_name":"MESH","db_id":"D019821"}]},{"id":"8609","type":"Disease","text":["myopathy"],"offsets":[[751,759]],"normalized":[{"db_name":"MESH","db_id":"D009135"}]},{"id":"8610","type":"Disease","text":["myopathy"],"offsets":[[868,876]],"normalized":[{"db_name":"MESH","db_id":"D009135"}]},{"id":"8611","type":"Chemical","text":["statins"],"offsets":[[923,930]],"normalized":[{"db_name":"MESH","db_id":"D019821"}]}],"events":[],"coreferences":[],"relations":[{"id":"8612","type":"CID","arg1_id":"8598","arg2_id":"8604","normalized":[]},{"id":"8613","type":"CID","arg1_id":"8598","arg2_id":"8605","normalized":[]},{"id":"8614","type":"CID","arg1_id":"8599","arg2_id":"8604","normalized":[]},{"id":"8615","type":"CID","arg1_id":"8599","arg2_id":"8605","normalized":[]},{"id":"8616","type":"CID","arg1_id":"8602","arg2_id":"8604","normalized":[]},{"id":"8617","type":"CID","arg1_id":"8602","arg2_id":"8605","normalized":[]},{"id":"8618","type":"CID","arg1_id":"8608","arg2_id":"8604","normalized":[]},{"id":"8619","type":"CID","arg1_id":"8608","arg2_id":"8605","normalized":[]},{"id":"8620","type":"CID","arg1_id":"8611","arg2_id":"8604","normalized":[]},{"id":"8621","type":"CID","arg1_id":"8611","arg2_id":"8605","normalized":[]},{"id":"8622","type":"CID","arg1_id":"8598","arg2_id":"8597","normalized":[]},{"id":"8623","type":"CID","arg1_id":"8598","arg2_id":"8600","normalized":[]},{"id":"8624","type":"CID","arg1_id":"8598","arg2_id":"8603","normalized":[]},{"id":"8625","type":"CID","arg1_id":"8598","arg2_id":"8609","normalized":[]},{"id":"8626","type":"CID","arg1_id":"8598","arg2_id":"8610","normalized":[]},{"id":"8627","type":"CID","arg1_id":"8599","arg2_id":"8597","normalized":[]},{"id":"8628","type":"CID","arg1_id":"8599","arg2_id":"8600","normalized":[]},{"id":"8629","type":"CID","arg1_id":"8599","arg2_id":"8603","normalized":[]},{"id":"8630","type":"CID","arg1_id":"8599","arg2_id":"8609","normalized":[]},{"id":"8631","type":"CID","arg1_id":"8599","arg2_id":"8610","normalized":[]},{"id":"8632","type":"CID","arg1_id":"8602","arg2_id":"8597","normalized":[]},{"id":"8633","type":"CID","arg1_id":"8602","arg2_id":"8600","normalized":[]},{"id":"8634","type":"CID","arg1_id":"8602","arg2_id":"8603","normalized":[]},{"id":"8635","type":"CID","arg1_id":"8602","arg2_id":"8609","normalized":[]},{"id":"8636","type":"CID","arg1_id":"8602","arg2_id":"8610","normalized":[]},{"id":"8637","type":"CID","arg1_id":"8608","arg2_id":"8597","normalized":[]},{"id":"8638","type":"CID","arg1_id":"8608","arg2_id":"8600","normalized":[]},{"id":"8639","type":"CID","arg1_id":"8608","arg2_id":"8603","normalized":[]},{"id":"8640","type":"CID","arg1_id":"8608","arg2_id":"8609","normalized":[]},{"id":"8641","type":"CID","arg1_id":"8608","arg2_id":"8610","normalized":[]},{"id":"8642","type":"CID","arg1_id":"8611","arg2_id":"8597","normalized":[]},{"id":"8643","type":"CID","arg1_id":"8611","arg2_id":"8600","normalized":[]},{"id":"8644","type":"CID","arg1_id":"8611","arg2_id":"8603","normalized":[]},{"id":"8645","type":"CID","arg1_id":"8611","arg2_id":"8609","normalized":[]},{"id":"8646","type":"CID","arg1_id":"8611","arg2_id":"8610","normalized":[]}]}
{"id":"8647","document_id":"17261653","passages":[{"id":"8648","type":"title","text":["Direct inhibition of cardiac hyperpolarization-activated cyclic nucleotide-gated pacemaker channels by clonidine."],"offsets":[[0,113]]},{"id":"8649","type":"abstract","text":["BACKGROUND: Inhibition of cardiac sympathetic tone represents an important strategy for treatment of cardiovascular disease, including arrhythmia, coronary heart disease, and chronic heart failure. Activation of presynaptic alpha2-adrenoceptors is the most widely accepted mechanism of action of the antisympathetic drug clonidine; however, other target proteins have been postulated to contribute to the in vivo actions of clonidine. METHODS AND RESULTS: To test whether clonidine elicits pharmacological effects independent of alpha2-adrenoceptors, we have generated mice with a targeted deletion of all 3 alpha2-adrenoceptor subtypes (alpha2ABC-\/-). Alpha2ABC-\/- mice were completely unresponsive to the analgesic and hypnotic effects of clonidine; however, clonidine significantly lowered heart rate in alpha2ABC-\/- mice by up to 150 bpm. Clonidine-induced bradycardia in conscious alpha2ABC-\/- mice was 32.3% (10 microg\/kg) and 26.6% (100 microg\/kg) of the effect in wild-type mice. A similar bradycardic effect of clonidine was observed in isolated spontaneously beating right atria from alpha2ABC-knockout and wild-type mice. Clonidine inhibited the native pacemaker current (I(f)) in isolated sinoatrial node pacemaker cells and the I(f)-generating hyperpolarization-activated cyclic nucleotide-gated (HCN) 2 and HCN4 channels in transfected HEK293 cells. As a consequence of blocking I(f), clonidine reduced the slope of the diastolic depolarization and the frequency of pacemaker potentials in sinoatrial node cells from wild-type and alpha2ABC-knockout mice. CONCLUSIONS: Direct inhibition of cardiac HCN pacemaker channels contributes to the bradycardic effects of clonidine gene-targeted mice in vivo, and thus, clonidine-like drugs represent novel structures for future HCN channel inhibitors."],"offsets":[[114,1921]]}],"entities":[{"id":"8650","type":"Chemical","text":["cyclic nucleotide"],"offsets":[[57,74]],"normalized":[{"db_name":"MESH","db_id":"D009712"}]},{"id":"8651","type":"Chemical","text":["clonidine"],"offsets":[[103,112]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]},{"id":"8652","type":"Disease","text":["cardiovascular disease"],"offsets":[[215,237]],"normalized":[{"db_name":"MESH","db_id":"D002318"}]},{"id":"8653","type":"Disease","text":["arrhythmia"],"offsets":[[249,259]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"8654","type":"Disease","text":["coronary heart disease"],"offsets":[[261,283]],"normalized":[{"db_name":"MESH","db_id":"D003327"}]},{"id":"8655","type":"Disease","text":["heart failure"],"offsets":[[297,310]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]},{"id":"8656","type":"Chemical","text":["clonidine"],"offsets":[[435,444]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]},{"id":"8657","type":"Chemical","text":["clonidine"],"offsets":[[538,547]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]},{"id":"8658","type":"Chemical","text":["clonidine"],"offsets":[[586,595]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]},{"id":"8659","type":"Chemical","text":["clonidine"],"offsets":[[855,864]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]},{"id":"8660","type":"Chemical","text":["clonidine"],"offsets":[[875,884]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]},{"id":"8661","type":"Chemical","text":["Clonidine"],"offsets":[[957,966]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]},{"id":"8662","type":"Disease","text":["bradycardia"],"offsets":[[975,986]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"8663","type":"Chemical","text":["clonidine"],"offsets":[[1134,1143]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]},{"id":"8664","type":"Chemical","text":["Clonidine"],"offsets":[[1247,1256]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]},{"id":"8665","type":"Chemical","text":["cyclic nucleotide"],"offsets":[[1399,1416]],"normalized":[{"db_name":"MESH","db_id":"D009712"}]},{"id":"8666","type":"Chemical","text":["clonidine"],"offsets":[[1513,1522]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]},{"id":"8667","type":"Chemical","text":["clonidine"],"offsets":[[1791,1800]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]},{"id":"8668","type":"Chemical","text":["clonidine"],"offsets":[[1839,1848]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]}],"events":[],"coreferences":[],"relations":[{"id":"8669","type":"CID","arg1_id":"8651","arg2_id":"8662","normalized":[]},{"id":"8670","type":"CID","arg1_id":"8656","arg2_id":"8662","normalized":[]},{"id":"8671","type":"CID","arg1_id":"8657","arg2_id":"8662","normalized":[]},{"id":"8672","type":"CID","arg1_id":"8658","arg2_id":"8662","normalized":[]},{"id":"8673","type":"CID","arg1_id":"8659","arg2_id":"8662","normalized":[]},{"id":"8674","type":"CID","arg1_id":"8660","arg2_id":"8662","normalized":[]},{"id":"8675","type":"CID","arg1_id":"8661","arg2_id":"8662","normalized":[]},{"id":"8676","type":"CID","arg1_id":"8663","arg2_id":"8662","normalized":[]},{"id":"8677","type":"CID","arg1_id":"8664","arg2_id":"8662","normalized":[]},{"id":"8678","type":"CID","arg1_id":"8666","arg2_id":"8662","normalized":[]},{"id":"8679","type":"CID","arg1_id":"8667","arg2_id":"8662","normalized":[]},{"id":"8680","type":"CID","arg1_id":"8668","arg2_id":"8662","normalized":[]}]}
{"id":"8681","document_id":"17343925","passages":[{"id":"8682","type":"title","text":["Influence of smoking on developing cochlea. Does smoking during pregnancy affect the amplitudes of transient evoked otoacoustic emissions in newborns?"],"offsets":[[0,150]]},{"id":"8683","type":"abstract","text":["OBJECTIVE: Maternal tobacco smoking has negative effects on fetal growth. The influence of smoking during pregnancy on the developing cochlea has not been estimated, although smoking has been positively associated with hearing loss in adults. The objective of this study was to determine the effects of maternal smoking on transient evoked otoacoustic emissions (TEOAEs) of healthy neonates. METHODS: This study was undertaken as part of neonatal screening for hearing impairment and involved both ears of 200 newborns. Newborns whose mothers reported smoking during pregnancy (n=200 ears) were compared to a control group of newborns (n=200 ears), whose mothers were non-smokers. Exposure to tobacco was characterized as low (<5 cigarettes per day, n=88 ears), moderate (5< or =cigarettes per day<10, n=76) or high (> or =10 cigarettes per day, n=36). RESULTS: In exposed neonates, TEOAEs mean response (across frequency) and mean amplitude at 4000Hz was significantly lower than in non-exposed neonates. Comparisons between exposed newborns' subgroups revealed no significant differences. However, by comparing each subgroup to control group, we found statistically significant decreases of TEOAEs amplitudes at 4000Hz for all three groups. Mean TEOAEs responses of highly exposed newborns were also significantly lower in comparison to our control group. CONCLUSION: In utero, exposure to tobacco smoking seems to have a small impact on outer hair cells. These effects seem to be equally true for all exposed newborns, regardless of the degree of exposure. Further studies are needed in order to establish a potential negative effect of maternal smoking on the neonate's hearing acuity."],"offsets":[[151,1840]]}],"entities":[{"id":"8684","type":"Chemical","text":["smoking"],"offsets":[[13,20]],"normalized":[{"db_name":"MESH","db_id":"D012906"}]},{"id":"8685","type":"Chemical","text":["smoking"],"offsets":[[49,56]],"normalized":[{"db_name":"MESH","db_id":"D012906"}]},{"id":"8686","type":"Chemical","text":["smoking"],"offsets":[[179,186]],"normalized":[{"db_name":"MESH","db_id":"D012906"}]},{"id":"8687","type":"Chemical","text":["smoking"],"offsets":[[242,249]],"normalized":[{"db_name":"MESH","db_id":"D012906"}]},{"id":"8688","type":"Chemical","text":["smoking"],"offsets":[[326,333]],"normalized":[{"db_name":"MESH","db_id":"D012906"}]},{"id":"8689","type":"Disease","text":["hearing loss"],"offsets":[[370,382]],"normalized":[{"db_name":"MESH","db_id":"D034381"}]},{"id":"8690","type":"Chemical","text":["smoking"],"offsets":[[463,470]],"normalized":[{"db_name":"MESH","db_id":"D012906"}]},{"id":"8691","type":"Disease","text":["hearing impairment"],"offsets":[[612,630]],"normalized":[{"db_name":"MESH","db_id":"D034381"}]},{"id":"8692","type":"Chemical","text":["smoking"],"offsets":[[703,710]],"normalized":[{"db_name":"MESH","db_id":"D012906"}]},{"id":"8693","type":"Disease","text":["decreases of TEOAEs amplitudes"],"offsets":[[1331,1361]],"normalized":[]},{"id":"8694","type":"Chemical","text":["smoking"],"offsets":[[1551,1558]],"normalized":[{"db_name":"MESH","db_id":"D012906"}]},{"id":"8695","type":"Chemical","text":["smoking"],"offsets":[[1800,1807]],"normalized":[{"db_name":"MESH","db_id":"D012906"}]}],"events":[],"coreferences":[],"relations":[{"id":"8696","type":"CID","arg1_id":"8684","arg2_id":"8689","normalized":[]},{"id":"8697","type":"CID","arg1_id":"8684","arg2_id":"8691","normalized":[]},{"id":"8698","type":"CID","arg1_id":"8685","arg2_id":"8689","normalized":[]},{"id":"8699","type":"CID","arg1_id":"8685","arg2_id":"8691","normalized":[]},{"id":"8700","type":"CID","arg1_id":"8686","arg2_id":"8689","normalized":[]},{"id":"8701","type":"CID","arg1_id":"8686","arg2_id":"8691","normalized":[]},{"id":"8702","type":"CID","arg1_id":"8687","arg2_id":"8689","normalized":[]},{"id":"8703","type":"CID","arg1_id":"8687","arg2_id":"8691","normalized":[]},{"id":"8704","type":"CID","arg1_id":"8688","arg2_id":"8689","normalized":[]},{"id":"8705","type":"CID","arg1_id":"8688","arg2_id":"8691","normalized":[]},{"id":"8706","type":"CID","arg1_id":"8690","arg2_id":"8689","normalized":[]},{"id":"8707","type":"CID","arg1_id":"8690","arg2_id":"8691","normalized":[]},{"id":"8708","type":"CID","arg1_id":"8692","arg2_id":"8689","normalized":[]},{"id":"8709","type":"CID","arg1_id":"8692","arg2_id":"8691","normalized":[]},{"id":"8710","type":"CID","arg1_id":"8694","arg2_id":"8689","normalized":[]},{"id":"8711","type":"CID","arg1_id":"8694","arg2_id":"8691","normalized":[]},{"id":"8712","type":"CID","arg1_id":"8695","arg2_id":"8689","normalized":[]},{"id":"8713","type":"CID","arg1_id":"8695","arg2_id":"8691","normalized":[]}]}
{"id":"8714","document_id":"17400887","passages":[{"id":"8715","type":"title","text":["Neuroinflammation and behavioral abnormalities after neonatal terbutaline treatment in rats: implications for autism."],"offsets":[[0,117]]},{"id":"8716","type":"abstract","text":["Autism is a neurodevelopmental disorder presenting before 3 years of age with deficits in communication and social skills and repetitive behaviors. In addition to genetic influences, recent studies suggest that prenatal drug or chemical exposures are risk factors for autism. Terbutaline, a beta2-adrenoceptor agonist used to arrest preterm labor, has been associated with increased concordance for autism in dizygotic twins. We studied the effects of terbutaline on microglial activation in different brain regions and behavioral outcomes in developing rats. Newborn rats were given terbutaline (10 mg\/kg) daily on postnatal days (PN) 2 to 5 or PN 11 to 14 and examined 24 h after the last dose and at PN 30. Immunohistochemical studies showed that administration of terbutaline on PN 2 to 5 produced a robust increase in microglial activation on PN 30 in the cerebral cortex, as well as in cerebellar and cerebrocortical white matter. None of these effects occurred in animals given terbutaline on PN 11 to 14. In behavioral tests, animals treated with terbutaline on PN 2 to 5 showed consistent patterns of hyper-reactivity to novelty and aversive stimuli when assessed in a novel open field, as well as in the acoustic startle response test. Our findings indicate that beta2-adrenoceptor overstimulation during an early critical period results in microglial activation associated with innate neuroinflammatory pathways and behavioral abnormalities, similar to those described in autism. This study provides a useful animal model for understanding the neuropathological processes underlying autism spectrum disorders."],"offsets":[[118,1738]]}],"entities":[{"id":"8717","type":"Disease","text":["Neuroinflammation"],"offsets":[[0,17]],"normalized":[{"db_name":"MESH","db_id":"D020078"}]},{"id":"8718","type":"Disease","text":["behavioral abnormalities"],"offsets":[[22,46]],"normalized":[{"db_name":"MESH","db_id":"D001523"}]},{"id":"8719","type":"Chemical","text":["terbutaline"],"offsets":[[62,73]],"normalized":[{"db_name":"MESH","db_id":"D013726"}]},{"id":"8720","type":"Disease","text":["autism"],"offsets":[[110,116]],"normalized":[{"db_name":"MESH","db_id":"D001321"}]},{"id":"8721","type":"Disease","text":["Autism"],"offsets":[[118,124]],"normalized":[{"db_name":"MESH","db_id":"D001321"}]},{"id":"8722","type":"Disease","text":["neurodevelopmental disorder"],"offsets":[[130,157]],"normalized":[{"db_name":"MESH","db_id":"D002658"}]},{"id":"8723","type":"Disease","text":["deficits in communication and social skills"],"offsets":[[196,239]],"normalized":[{"db_name":"MESH","db_id":"D003147"}]},{"id":"8724","type":"Disease","text":["repetitive behaviors"],"offsets":[[244,264]],"normalized":[{"db_name":"MESH","db_id":"D001523"}]},{"id":"8725","type":"Disease","text":["autism"],"offsets":[[386,392]],"normalized":[{"db_name":"MESH","db_id":"D001321"}]},{"id":"8726","type":"Chemical","text":["Terbutaline"],"offsets":[[394,405]],"normalized":[{"db_name":"MESH","db_id":"D013726"}]},{"id":"8727","type":"Disease","text":["preterm labor"],"offsets":[[451,464]],"normalized":[{"db_name":"MESH","db_id":"D007752"}]},{"id":"8728","type":"Disease","text":["autism"],"offsets":[[517,523]],"normalized":[{"db_name":"MESH","db_id":"D001321"}]},{"id":"8729","type":"Chemical","text":["terbutaline"],"offsets":[[570,581]],"normalized":[{"db_name":"MESH","db_id":"D013726"}]},{"id":"8730","type":"Chemical","text":["terbutaline"],"offsets":[[702,713]],"normalized":[{"db_name":"MESH","db_id":"D013726"}]},{"id":"8731","type":"Chemical","text":["terbutaline"],"offsets":[[886,897]],"normalized":[{"db_name":"MESH","db_id":"D013726"}]},{"id":"8732","type":"Chemical","text":["terbutaline"],"offsets":[[1103,1114]],"normalized":[{"db_name":"MESH","db_id":"D013726"}]},{"id":"8733","type":"Chemical","text":["terbutaline"],"offsets":[[1173,1184]],"normalized":[{"db_name":"MESH","db_id":"D013726"}]},{"id":"8734","type":"Disease","text":["behavioral abnormalities"],"offsets":[[1545,1569]],"normalized":[{"db_name":"MESH","db_id":"D001523"}]},{"id":"8735","type":"Disease","text":["autism"],"offsets":[[1601,1607]],"normalized":[{"db_name":"MESH","db_id":"D001321"}]},{"id":"8736","type":"Disease","text":["autism spectrum disorders"],"offsets":[[1712,1737]],"normalized":[{"db_name":"MESH","db_id":"D002659"}]}],"events":[],"coreferences":[],"relations":[{"id":"8737","type":"CID","arg1_id":"8719","arg2_id":"8720","normalized":[]},{"id":"8738","type":"CID","arg1_id":"8719","arg2_id":"8721","normalized":[]},{"id":"8739","type":"CID","arg1_id":"8719","arg2_id":"8725","normalized":[]},{"id":"8740","type":"CID","arg1_id":"8719","arg2_id":"8728","normalized":[]},{"id":"8741","type":"CID","arg1_id":"8719","arg2_id":"8735","normalized":[]},{"id":"8742","type":"CID","arg1_id":"8726","arg2_id":"8720","normalized":[]},{"id":"8743","type":"CID","arg1_id":"8726","arg2_id":"8721","normalized":[]},{"id":"8744","type":"CID","arg1_id":"8726","arg2_id":"8725","normalized":[]},{"id":"8745","type":"CID","arg1_id":"8726","arg2_id":"8728","normalized":[]},{"id":"8746","type":"CID","arg1_id":"8726","arg2_id":"8735","normalized":[]},{"id":"8747","type":"CID","arg1_id":"8729","arg2_id":"8720","normalized":[]},{"id":"8748","type":"CID","arg1_id":"8729","arg2_id":"8721","normalized":[]},{"id":"8749","type":"CID","arg1_id":"8729","arg2_id":"8725","normalized":[]},{"id":"8750","type":"CID","arg1_id":"8729","arg2_id":"8728","normalized":[]},{"id":"8751","type":"CID","arg1_id":"8729","arg2_id":"8735","normalized":[]},{"id":"8752","type":"CID","arg1_id":"8730","arg2_id":"8720","normalized":[]},{"id":"8753","type":"CID","arg1_id":"8730","arg2_id":"8721","normalized":[]},{"id":"8754","type":"CID","arg1_id":"8730","arg2_id":"8725","normalized":[]},{"id":"8755","type":"CID","arg1_id":"8730","arg2_id":"8728","normalized":[]},{"id":"8756","type":"CID","arg1_id":"8730","arg2_id":"8735","normalized":[]},{"id":"8757","type":"CID","arg1_id":"8731","arg2_id":"8720","normalized":[]},{"id":"8758","type":"CID","arg1_id":"8731","arg2_id":"8721","normalized":[]},{"id":"8759","type":"CID","arg1_id":"8731","arg2_id":"8725","normalized":[]},{"id":"8760","type":"CID","arg1_id":"8731","arg2_id":"8728","normalized":[]},{"id":"8761","type":"CID","arg1_id":"8731","arg2_id":"8735","normalized":[]},{"id":"8762","type":"CID","arg1_id":"8732","arg2_id":"8720","normalized":[]},{"id":"8763","type":"CID","arg1_id":"8732","arg2_id":"8721","normalized":[]},{"id":"8764","type":"CID","arg1_id":"8732","arg2_id":"8725","normalized":[]},{"id":"8765","type":"CID","arg1_id":"8732","arg2_id":"8728","normalized":[]},{"id":"8766","type":"CID","arg1_id":"8732","arg2_id":"8735","normalized":[]},{"id":"8767","type":"CID","arg1_id":"8733","arg2_id":"8720","normalized":[]},{"id":"8768","type":"CID","arg1_id":"8733","arg2_id":"8721","normalized":[]},{"id":"8769","type":"CID","arg1_id":"8733","arg2_id":"8725","normalized":[]},{"id":"8770","type":"CID","arg1_id":"8733","arg2_id":"8728","normalized":[]},{"id":"8771","type":"CID","arg1_id":"8733","arg2_id":"8735","normalized":[]}]}
{"id":"8772","document_id":"17612891","passages":[{"id":"8773","type":"title","text":["Acute myocarditis associated with clozapine."],"offsets":[[0,44]]},{"id":"8774","type":"abstract","text":["OBJECTIVE: A case of acute myocarditis associated with the commencement of clozapine is described, highlighting the onset, course and possible contributing factors. There is an urgent need to raise awareness about this potentially fatal complication of clozapine use. RESULTS: A 20-year-old male with schizophrenia developed a sudden onset of myocarditis after commencement of clozapine. The patient recovered with intensive medical support. The symptoms occurred around 2 weeks after starting clozapine in an inpatient setting. Possible contributing factors may have been concomitant antidepressant use and unaccustomed physical activity. CONCLUSIONS: Myocarditis is an increasingly recognized complication associated with the use of clozapine. It can be fatal if not recognized and treated early. Considering that clozapine remains the gold standard in treatment of resistant psychosis, there is an urgent need to raise awareness among medical and paramedical staff involved in the care of these patients. There are also implications for recommendations and regulations regarding the use of clozapine."],"offsets":[[45,1148]]}],"entities":[{"id":"8775","type":"Disease","text":["myocarditis"],"offsets":[[6,17]],"normalized":[{"db_name":"MESH","db_id":"D009205"}]},{"id":"8776","type":"Chemical","text":["clozapine"],"offsets":[[34,43]],"normalized":[{"db_name":"MESH","db_id":"D003024"}]},{"id":"8777","type":"Disease","text":["myocarditis"],"offsets":[[72,83]],"normalized":[{"db_name":"MESH","db_id":"D009205"}]},{"id":"8778","type":"Chemical","text":["clozapine"],"offsets":[[120,129]],"normalized":[{"db_name":"MESH","db_id":"D003024"}]},{"id":"8779","type":"Chemical","text":["clozapine"],"offsets":[[298,307]],"normalized":[{"db_name":"MESH","db_id":"D003024"}]},{"id":"8780","type":"Disease","text":["schizophrenia"],"offsets":[[346,359]],"normalized":[{"db_name":"MESH","db_id":"D012559"}]},{"id":"8781","type":"Disease","text":["myocarditis"],"offsets":[[388,399]],"normalized":[{"db_name":"MESH","db_id":"D009205"}]},{"id":"8782","type":"Chemical","text":["clozapine"],"offsets":[[422,431]],"normalized":[{"db_name":"MESH","db_id":"D003024"}]},{"id":"8783","type":"Chemical","text":["clozapine"],"offsets":[[539,548]],"normalized":[{"db_name":"MESH","db_id":"D003024"}]},{"id":"8784","type":"Chemical","text":["antidepressant"],"offsets":[[630,644]],"normalized":[{"db_name":"MESH","db_id":"D000928"}]},{"id":"8785","type":"Disease","text":["Myocarditis"],"offsets":[[698,709]],"normalized":[{"db_name":"MESH","db_id":"D009205"}]},{"id":"8786","type":"Chemical","text":["clozapine"],"offsets":[[780,789]],"normalized":[{"db_name":"MESH","db_id":"D003024"}]},{"id":"8787","type":"Chemical","text":["clozapine"],"offsets":[[861,870]],"normalized":[{"db_name":"MESH","db_id":"D003024"}]},{"id":"8788","type":"Disease","text":["psychosis"],"offsets":[[923,932]],"normalized":[{"db_name":"MESH","db_id":"D011618"}]},{"id":"8789","type":"Chemical","text":["clozapine"],"offsets":[[1138,1147]],"normalized":[{"db_name":"MESH","db_id":"D003024"}]}],"events":[],"coreferences":[],"relations":[{"id":"8790","type":"CID","arg1_id":"8776","arg2_id":"8775","normalized":[]},{"id":"8791","type":"CID","arg1_id":"8776","arg2_id":"8777","normalized":[]},{"id":"8792","type":"CID","arg1_id":"8776","arg2_id":"8781","normalized":[]},{"id":"8793","type":"CID","arg1_id":"8776","arg2_id":"8785","normalized":[]},{"id":"8794","type":"CID","arg1_id":"8778","arg2_id":"8775","normalized":[]},{"id":"8795","type":"CID","arg1_id":"8778","arg2_id":"8777","normalized":[]},{"id":"8796","type":"CID","arg1_id":"8778","arg2_id":"8781","normalized":[]},{"id":"8797","type":"CID","arg1_id":"8778","arg2_id":"8785","normalized":[]},{"id":"8798","type":"CID","arg1_id":"8779","arg2_id":"8775","normalized":[]},{"id":"8799","type":"CID","arg1_id":"8779","arg2_id":"8777","normalized":[]},{"id":"8800","type":"CID","arg1_id":"8779","arg2_id":"8781","normalized":[]},{"id":"8801","type":"CID","arg1_id":"8779","arg2_id":"8785","normalized":[]},{"id":"8802","type":"CID","arg1_id":"8782","arg2_id":"8775","normalized":[]},{"id":"8803","type":"CID","arg1_id":"8782","arg2_id":"8777","normalized":[]},{"id":"8804","type":"CID","arg1_id":"8782","arg2_id":"8781","normalized":[]},{"id":"8805","type":"CID","arg1_id":"8782","arg2_id":"8785","normalized":[]},{"id":"8806","type":"CID","arg1_id":"8783","arg2_id":"8775","normalized":[]},{"id":"8807","type":"CID","arg1_id":"8783","arg2_id":"8777","normalized":[]},{"id":"8808","type":"CID","arg1_id":"8783","arg2_id":"8781","normalized":[]},{"id":"8809","type":"CID","arg1_id":"8783","arg2_id":"8785","normalized":[]},{"id":"8810","type":"CID","arg1_id":"8786","arg2_id":"8775","normalized":[]},{"id":"8811","type":"CID","arg1_id":"8786","arg2_id":"8777","normalized":[]},{"id":"8812","type":"CID","arg1_id":"8786","arg2_id":"8781","normalized":[]},{"id":"8813","type":"CID","arg1_id":"8786","arg2_id":"8785","normalized":[]},{"id":"8814","type":"CID","arg1_id":"8787","arg2_id":"8775","normalized":[]},{"id":"8815","type":"CID","arg1_id":"8787","arg2_id":"8777","normalized":[]},{"id":"8816","type":"CID","arg1_id":"8787","arg2_id":"8781","normalized":[]},{"id":"8817","type":"CID","arg1_id":"8787","arg2_id":"8785","normalized":[]},{"id":"8818","type":"CID","arg1_id":"8789","arg2_id":"8775","normalized":[]},{"id":"8819","type":"CID","arg1_id":"8789","arg2_id":"8777","normalized":[]},{"id":"8820","type":"CID","arg1_id":"8789","arg2_id":"8781","normalized":[]},{"id":"8821","type":"CID","arg1_id":"8789","arg2_id":"8785","normalized":[]},{"id":"8822","type":"CID","arg1_id":"8784","arg2_id":"8775","normalized":[]},{"id":"8823","type":"CID","arg1_id":"8784","arg2_id":"8777","normalized":[]},{"id":"8824","type":"CID","arg1_id":"8784","arg2_id":"8781","normalized":[]},{"id":"8825","type":"CID","arg1_id":"8784","arg2_id":"8785","normalized":[]}]}
{"id":"8826","document_id":"18081909","passages":[{"id":"8827","type":"title","text":["Encephalopathy induced by levetiracetam added to valproate."],"offsets":[[0,59]]},{"id":"8828","type":"abstract","text":["BACKGROUND: We report on the manifestation of a levetiracetam (LEV)-induced encephalopathy. FINDINGS: A 28-year-old man suffering from idiopathic epilepsy with generalized seizures was treated with LEV (3000 mg) added to valproate (VPA) (2000 mg). Frequency of generalized tonic-clonic seizures increased from one per 6 months to two per month. Neuropsychological testing showed impaired word fluency, psychomotor speed and working memory. The interictal electroencephalogram (EEG) showed a generalized slowing to 5 per second theta rhythms with bilateral generalized high-amplitude discharges. OUTCOME: Following discontinuation of LEV, EEG and neuropsychological findings improved and seizure frequency decreased."],"offsets":[[60,775]]}],"entities":[{"id":"8829","type":"Disease","text":["Encephalopathy"],"offsets":[[0,14]],"normalized":[{"db_name":"MESH","db_id":"D001927"}]},{"id":"8830","type":"Chemical","text":["levetiracetam"],"offsets":[[26,39]],"normalized":[{"db_name":"MESH","db_id":"C026098"}]},{"id":"8831","type":"Chemical","text":["valproate"],"offsets":[[49,58]],"normalized":[{"db_name":"MESH","db_id":"D014635"}]},{"id":"8832","type":"Chemical","text":["levetiracetam"],"offsets":[[108,121]],"normalized":[{"db_name":"MESH","db_id":"C026098"}]},{"id":"8833","type":"Chemical","text":["LEV"],"offsets":[[123,126]],"normalized":[{"db_name":"MESH","db_id":"C026098"}]},{"id":"8834","type":"Disease","text":["encephalopathy"],"offsets":[[136,150]],"normalized":[{"db_name":"MESH","db_id":"D001927"}]},{"id":"8835","type":"Disease","text":["idiopathic epilepsy"],"offsets":[[195,214]],"normalized":[{"db_name":"MESH","db_id":"C562694"}]},{"id":"8836","type":"Disease","text":["seizures"],"offsets":[[232,240]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"8837","type":"Chemical","text":["LEV"],"offsets":[[258,261]],"normalized":[{"db_name":"MESH","db_id":"C026098"}]},{"id":"8838","type":"Chemical","text":["valproate"],"offsets":[[281,290]],"normalized":[{"db_name":"MESH","db_id":"D014635"}]},{"id":"8839","type":"Chemical","text":["VPA"],"offsets":[[292,295]],"normalized":[{"db_name":"MESH","db_id":"D014635"}]},{"id":"8840","type":"Disease","text":["tonic-clonic seizures"],"offsets":[[333,354]],"normalized":[{"db_name":"MESH","db_id":"D004830"}]},{"id":"8841","type":"Disease","text":["impaired word fluency, psychomotor speed and working memory"],"offsets":[[439,498]],"normalized":[{"db_name":"MESH","db_id":"D008569"}]},{"id":"8842","type":"Chemical","text":["LEV"],"offsets":[[693,696]],"normalized":[{"db_name":"MESH","db_id":"C026098"}]},{"id":"8843","type":"Disease","text":["seizure"],"offsets":[[747,754]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]}],"events":[],"coreferences":[],"relations":[{"id":"8844","type":"CID","arg1_id":"8830","arg2_id":"8841","normalized":[]},{"id":"8845","type":"CID","arg1_id":"8832","arg2_id":"8841","normalized":[]},{"id":"8846","type":"CID","arg1_id":"8833","arg2_id":"8841","normalized":[]},{"id":"8847","type":"CID","arg1_id":"8837","arg2_id":"8841","normalized":[]},{"id":"8848","type":"CID","arg1_id":"8842","arg2_id":"8841","normalized":[]},{"id":"8849","type":"CID","arg1_id":"8831","arg2_id":"8841","normalized":[]},{"id":"8850","type":"CID","arg1_id":"8838","arg2_id":"8841","normalized":[]},{"id":"8851","type":"CID","arg1_id":"8839","arg2_id":"8841","normalized":[]},{"id":"8852","type":"CID","arg1_id":"8831","arg2_id":"8829","normalized":[]},{"id":"8853","type":"CID","arg1_id":"8831","arg2_id":"8834","normalized":[]},{"id":"8854","type":"CID","arg1_id":"8838","arg2_id":"8829","normalized":[]},{"id":"8855","type":"CID","arg1_id":"8838","arg2_id":"8834","normalized":[]},{"id":"8856","type":"CID","arg1_id":"8839","arg2_id":"8829","normalized":[]},{"id":"8857","type":"CID","arg1_id":"8839","arg2_id":"8834","normalized":[]},{"id":"8858","type":"CID","arg1_id":"8830","arg2_id":"8829","normalized":[]},{"id":"8859","type":"CID","arg1_id":"8830","arg2_id":"8834","normalized":[]},{"id":"8860","type":"CID","arg1_id":"8832","arg2_id":"8829","normalized":[]},{"id":"8861","type":"CID","arg1_id":"8832","arg2_id":"8834","normalized":[]},{"id":"8862","type":"CID","arg1_id":"8833","arg2_id":"8829","normalized":[]},{"id":"8863","type":"CID","arg1_id":"8833","arg2_id":"8834","normalized":[]},{"id":"8864","type":"CID","arg1_id":"8837","arg2_id":"8829","normalized":[]},{"id":"8865","type":"CID","arg1_id":"8837","arg2_id":"8834","normalized":[]},{"id":"8866","type":"CID","arg1_id":"8842","arg2_id":"8829","normalized":[]},{"id":"8867","type":"CID","arg1_id":"8842","arg2_id":"8834","normalized":[]},{"id":"8868","type":"CID","arg1_id":"8830","arg2_id":"8840","normalized":[]},{"id":"8869","type":"CID","arg1_id":"8832","arg2_id":"8840","normalized":[]},{"id":"8870","type":"CID","arg1_id":"8833","arg2_id":"8840","normalized":[]},{"id":"8871","type":"CID","arg1_id":"8837","arg2_id":"8840","normalized":[]},{"id":"8872","type":"CID","arg1_id":"8842","arg2_id":"8840","normalized":[]},{"id":"8873","type":"CID","arg1_id":"8831","arg2_id":"8840","normalized":[]},{"id":"8874","type":"CID","arg1_id":"8838","arg2_id":"8840","normalized":[]},{"id":"8875","type":"CID","arg1_id":"8839","arg2_id":"8840","normalized":[]}]}
{"id":"8876","document_id":"18083142","passages":[{"id":"8877","type":"title","text":["Norepinephrine signaling through beta-adrenergic receptors is critical for expression of cocaine-induced anxiety."],"offsets":[[0,113]]},{"id":"8878","type":"abstract","text":["BACKGROUND: Cocaine is a widely abused psychostimulant that has both rewarding and aversive properties. While the mechanisms underlying cocaine's rewarding effects have been studied extensively, less attention has been paid to the unpleasant behavioral states induced by cocaine, such as anxiety. METHODS: In this study, we evaluated the performance of dopamine beta-hydroxylase knockout (Dbh -\/-) mice, which lack norepinephrine (NE), in the elevated plus maze (EPM) to examine the contribution of noradrenergic signaling to cocaine-induced anxiety. RESULTS: We found that cocaine dose-dependently increased anxiety-like behavior in control (Dbh +\/-) mice, as measured by a decrease in open arm exploration. The Dbh -\/- mice had normal baseline performance in the EPM but were completely resistant to the anxiogenic effects of cocaine. Cocaine-induced anxiety was also attenuated in Dbh +\/- mice following administration of disulfiram, a dopamine beta-hydroxylase (DBH) inhibitor. In experiments using specific adrenergic antagonists, we found that pretreatment with the beta-adrenergic receptor antagonist propranolol blocked cocaine-induced anxiety-like behavior in Dbh +\/- and wild-type C57BL6\/J mice, while the alpha(1) antagonist prazosin and the alpha(2) antagonist yohimbine had no effect. CONCLUSIONS: These results indicate that noradrenergic signaling via beta-adrenergic receptors is required for cocaine-induced anxiety in mice."],"offsets":[[114,1555]]}],"entities":[{"id":"8879","type":"Chemical","text":["Norepinephrine"],"offsets":[[0,14]],"normalized":[{"db_name":"MESH","db_id":"D009638"}]},{"id":"8880","type":"Chemical","text":["cocaine"],"offsets":[[89,96]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"8881","type":"Disease","text":["anxiety"],"offsets":[[105,112]],"normalized":[{"db_name":"MESH","db_id":"D001008"}]},{"id":"8882","type":"Chemical","text":["Cocaine"],"offsets":[[126,133]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"8883","type":"Chemical","text":["cocaine"],"offsets":[[250,257]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"8884","type":"Chemical","text":["cocaine"],"offsets":[[385,392]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"8885","type":"Disease","text":["anxiety"],"offsets":[[402,409]],"normalized":[{"db_name":"MESH","db_id":"D001008"}]},{"id":"8886","type":"Chemical","text":["dopamine"],"offsets":[[467,475]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"8887","type":"Chemical","text":["norepinephrine"],"offsets":[[529,543]],"normalized":[{"db_name":"MESH","db_id":"D009638"}]},{"id":"8888","type":"Chemical","text":["NE"],"offsets":[[545,547]],"normalized":[{"db_name":"MESH","db_id":"D009638"}]},{"id":"8889","type":"Chemical","text":["cocaine"],"offsets":[[640,647]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"8890","type":"Disease","text":["anxiety"],"offsets":[[656,663]],"normalized":[{"db_name":"MESH","db_id":"D001008"}]},{"id":"8891","type":"Chemical","text":["cocaine"],"offsets":[[688,695]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"8892","type":"Disease","text":["anxiety"],"offsets":[[723,730]],"normalized":[{"db_name":"MESH","db_id":"D001008"}]},{"id":"8893","type":"Chemical","text":["cocaine"],"offsets":[[942,949]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"8894","type":"Chemical","text":["Cocaine"],"offsets":[[951,958]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"8895","type":"Disease","text":["anxiety"],"offsets":[[967,974]],"normalized":[{"db_name":"MESH","db_id":"D001008"}]},{"id":"8896","type":"Chemical","text":["disulfiram"],"offsets":[[1039,1049]],"normalized":[{"db_name":"MESH","db_id":"D004221"}]},{"id":"8897","type":"Chemical","text":["dopamine"],"offsets":[[1053,1061]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"8898","type":"Chemical","text":["propranolol"],"offsets":[[1222,1233]],"normalized":[{"db_name":"MESH","db_id":"D011433"}]},{"id":"8899","type":"Chemical","text":["cocaine"],"offsets":[[1242,1249]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"8900","type":"Disease","text":["anxiety"],"offsets":[[1258,1265]],"normalized":[{"db_name":"MESH","db_id":"D001008"}]},{"id":"8901","type":"Chemical","text":["prazosin"],"offsets":[[1350,1358]],"normalized":[{"db_name":"MESH","db_id":"D011224"}]},{"id":"8902","type":"Chemical","text":["yohimbine"],"offsets":[[1387,1396]],"normalized":[{"db_name":"MESH","db_id":"D015016"}]},{"id":"8903","type":"Chemical","text":["cocaine"],"offsets":[[1523,1530]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"8904","type":"Disease","text":["anxiety"],"offsets":[[1539,1546]],"normalized":[{"db_name":"MESH","db_id":"D001008"}]}],"events":[],"coreferences":[],"relations":[{"id":"8905","type":"CID","arg1_id":"8880","arg2_id":"8881","normalized":[]},{"id":"8906","type":"CID","arg1_id":"8880","arg2_id":"8885","normalized":[]},{"id":"8907","type":"CID","arg1_id":"8880","arg2_id":"8890","normalized":[]},{"id":"8908","type":"CID","arg1_id":"8880","arg2_id":"8892","normalized":[]},{"id":"8909","type":"CID","arg1_id":"8880","arg2_id":"8895","normalized":[]},{"id":"8910","type":"CID","arg1_id":"8880","arg2_id":"8900","normalized":[]},{"id":"8911","type":"CID","arg1_id":"8880","arg2_id":"8904","normalized":[]},{"id":"8912","type":"CID","arg1_id":"8882","arg2_id":"8881","normalized":[]},{"id":"8913","type":"CID","arg1_id":"8882","arg2_id":"8885","normalized":[]},{"id":"8914","type":"CID","arg1_id":"8882","arg2_id":"8890","normalized":[]},{"id":"8915","type":"CID","arg1_id":"8882","arg2_id":"8892","normalized":[]},{"id":"8916","type":"CID","arg1_id":"8882","arg2_id":"8895","normalized":[]},{"id":"8917","type":"CID","arg1_id":"8882","arg2_id":"8900","normalized":[]},{"id":"8918","type":"CID","arg1_id":"8882","arg2_id":"8904","normalized":[]},{"id":"8919","type":"CID","arg1_id":"8883","arg2_id":"8881","normalized":[]},{"id":"8920","type":"CID","arg1_id":"8883","arg2_id":"8885","normalized":[]},{"id":"8921","type":"CID","arg1_id":"8883","arg2_id":"8890","normalized":[]},{"id":"8922","type":"CID","arg1_id":"8883","arg2_id":"8892","normalized":[]},{"id":"8923","type":"CID","arg1_id":"8883","arg2_id":"8895","normalized":[]},{"id":"8924","type":"CID","arg1_id":"8883","arg2_id":"8900","normalized":[]},{"id":"8925","type":"CID","arg1_id":"8883","arg2_id":"8904","normalized":[]},{"id":"8926","typ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{"id":"8975","document_id":"18182964","passages":[{"id":"8976","type":"title","text":["Clonidine for attention-deficit\/hyperactivity disorder: II. ECG changes and adverse events analysis."],"offsets":[[0,100]]},{"id":"8977","type":"abstract","text":["OBJECTIVE: To examine the safety and tolerability of clonidine used alone or with methylphenidate in children with attention-deficit\/hyperactivity disorder (ADHD). METHOD: In a 16-week multicenter, double-blind trial, 122 children with ADHD were randomly assigned to clonidine (n = 31), methylphenidate (n = 29), clonidine and methylphenidate (n = 32), or placebo (n = 30). Doses were flexibly titrated up to 0.6 mg\/day for clonidine and 60 mg\/day for methylphenidate (both with divided dosing). Groups were compared regarding adverse events and changes from baseline to week 16 in electrocardiograms and vital signs. RESULTS: There were more incidents of bradycardia in subjects treated with clonidine compared with those not treated with clonidine (17.5% versus 3.4%; p =.02), but no other significant group differences regarding electrocardiogram and other cardiovascular outcomes. There were no suggestions of interactions between clonidine and methylphenidate regarding cardiovascular outcomes. Moderate or severe adverse events were more common in subjects on clonidine (79.4% versus 49.2%; p =.0006) but not associated with higher rates of early study withdrawal. Drowsiness was common on clonidine, but generally resolved by 6 to 8 weeks. CONCLUSIONS: Clonidine, used alone or with methylphenidate, appears safe and well tolerated in childhood ADHD. Physicians prescribing clonidine should monitor for bradycardia and advise patients about the high likelihood of initial drowsiness."],"offsets":[[101,1591]]}],"entities":[{"id":"8978","type":"Chemical","text":["Clonidine"],"offsets":[[0,9]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]},{"id":"8979","type":"Disease","text":["attention-deficit\/hyperactivity disorder"],"offsets":[[14,54]],"normalized":[{"db_name":"MESH","db_id":"D001289"}]},{"id":"8980","type":"Chemical","text":["clonidine"],"offsets":[[154,163]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]},{"id":"8981","type":"Chemical","text":["methylphenidate"],"offsets":[[183,198]],"normalized":[{"db_name":"MESH","db_id":"D008774"}]},{"id":"8982","type":"Disease","text":["attention-deficit\/hyperactivity disorder"],"offsets":[[216,256]],"normalized":[{"db_name":"MESH","db_id":"D001289"}]},{"id":"8983","type":"Disease","text":["ADHD"],"offsets":[[258,262]],"normalized":[{"db_name":"MESH","db_id":"D001289"}]},{"id":"8984","type":"Disease","text":["ADHD"],"offsets":[[337,341]],"normalized":[{"db_name":"MESH","db_id":"D001289"}]},{"id":"8985","type":"Chemical","text":["clonidine"],"offsets":[[368,377]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]},{"id":"8986","type":"Chemical","text":["methylphenidate"],"offsets":[[388,403]],"normalized":[{"db_name":"MESH","db_id":"D008774"}]},{"id":"8987","type":"Chemical","text":["clonidine"],"offsets":[[414,423]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]},{"id":"8988","type":"Chemical","text":["methylphenidate"],"offsets":[[428,443]],"normalized":[{"db_name":"MESH","db_id":"D008774"}]},{"id":"8989","type":"Chemical","text":["clonidine"],"offsets":[[525,534]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]},{"id":"8990","type":"Chemical","text":["methylphenidate"],"offsets":[[553,568]],"normalized":[{"db_name":"MESH","db_id":"D008774"}]},{"id":"8991","type":"Disease","text":["bradycardia"],"offsets":[[757,768]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"8992","type":"Chemical","text":["clonidine"],"offsets":[[794,803]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]},{"id":"8993","type":"Chemical","text":["clonidine"],"offsets":[[841,850]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]},{"id":"8994","type":"Chemical","text":["clonidine"],"offsets":[[1036,1045]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]},{"id":"8995","type":"Chemical","text":["methylphenidate"],"offsets":[[1050,1065]],"normalized":[{"db_name":"MESH","db_id":"D008774"}]},{"id":"8996","type":"Chemical","text":["clonidine"],"offsets":[[1167,1176]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]},{"id":"8997","type":"Disease","text":["Drowsiness"],"offsets":[[1272,1282]],"normalized":[{"db_name":"MESH","db_id":"D006970"}]},{"id":"8998","type":"Chemical","text":["clonidine"],"offsets":[[1297,1306]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]},{"id":"8999","type":"Chemical","text":["Clonidine"],"offsets":[[1361,1370]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]},{"id":"9000","type":"Chemical","text":["methylphenidate"],"offsets":[[1391,1406]],"normalized":[{"db_name":"MESH","db_id":"D008774"}]},{"id":"9001","type":"Disease","text":["ADHD"],"offsets":[[1453,1457]],"normalized":[{"db_name":"MESH","db_id":"D001289"}]},{"id":"9002","type":"Chemical","text":["clonidine"],"offsets":[[1482,1491]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]},{"id":"9003","type":"Disease","text":["bradycardia"],"offsets":[[1511,1522]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"9004","type":"Disease","text":["drowsiness"],"offsets":[[1580,1590]],"normalized":[{"db_name":"MESH","db_id":"D006970"}]}],"events":[],"coreferences":[],"relations":[{"id":"9005","type":"CID","arg1_id":"8978","arg2_id":"8991","normalized":[]},{"id":"9006","type":"CID","arg1_id":"8978","arg2_id":"9003","normalized":[]},{"id":"9007","type":"CID","arg1_id":"8980","arg2_id":"8991","normalized":[]},{"id":"9008","type":"CID","arg1_id":"8980","arg2_id":"9003","normalized":[]},{"id":"9009","type":"CID","arg1_id":"8985","arg2_id":"8991","normalized":[]},{"id":"9010","type":"CID","arg1_id":"8985","arg2_id":"9003","normalized":[]},{"id":"9011","type":"CID","arg1_id":"8987","arg2_id":"8991","normalized":[]},{"id":"9012","type":"CID","arg1_id":"8987","arg2_id":"9003","normalized":[]},{"id":"9013","type":"CID","arg1_id":"8989","arg2_id":"8991","normalized":[]},{"id":"9014","type":"CID","arg1_id":"8989","arg2_id":"9003","normalized":[]},{"id":"9015","type":"CID","arg1_id":"8992","arg2_id":"8991","normalized":[]},{"id":"9016","type":"CID","arg1_id":"8992","arg2_id":"9003","normalized":[]},{"id":"9017","type":"CID","arg1_id":"8993","arg2_id":"8991","normalized":[]},{"id":"9018","type":"CID","arg1_id":"8993","arg2_id":"9003","normalized":[]},{"id":"9019","type":"CID","arg1_id":"8994","arg2_id":"8991","normalized":[]},{"id":"9020","type":"CID","arg1_id":"8994","arg2_id":"9003","normalized":[]},{"id":"9021","type":"CID","arg1_id":"8996","arg2_id":"8991","normalized":[]},{"id":"9022","type":"CID","arg1_id":"8996","arg2_id":"9003","normalized":[]},{"id":"9023","type":"CID","arg1_id":"8998","arg2_id":"8991","normalized":[]},{"id":"9024","type":"CID","arg1_id":"8998","arg2_id":"9003","normalized":[]},{"id":"9025","type":"CID","arg1_id":"8999","arg2_id":"8991","normalized":[]},{"id":"9026","type":"CID","arg1_id":"8999","arg2_id":"9003","normalized":[]},{"id":"9027","type":"CID","arg1_id":"9002","arg2_id":"8991","normalized":[]},{"id":"9028","type":"CID","arg1_id":"9002","arg2_id":"9003","normalized":[]}]}
{"id":"9029","document_id":"18217897","passages":[{"id":"9030","type":"title","text":["Thalidomide has limited single-agent activity in relapsed or refractory indolent non-Hodgkin lymphomas: a phase II trial of the Cancer and Leukemia Group B."],"offsets":[[0,156]]},{"id":"9031","type":"abstract","text":["Thalidomide is an immunomodulatory agent with demonstrated activity in multiple myeloma, mantle cell lymphoma and lymphoplasmacytic lymphoma. Its activity is believed to be due modulation of the tumour milieu, including downregulation of angiogenesis and inflammatory cytokines. Between July 2001 and April 2004, 24 patients with relapsed\/refractory indolent lymphomas received thalidomide 200 mg daily with escalation by 100 mg daily every 1-2 weeks as tolerated, up to a maximum of 800 mg daily. Patients had received a median of 2 (range, 1-4) prior regimens. Of 24 evaluable patients, two achieved a complete remission and one achieved a partial remission for an overall response rate of 12.5% (95% confidence interval: 2.6-32.4%). Eleven patients progressed during therapy. Grade 3-4 adverse effects included myelosuppression, fatigue, somnolence\/depressed mood, neuropathy and dyspnea. Of concern was the occurrence of four thromboembolic events. Our results failed to demonstrate an important response rate to single agent thalidomide in indolent lymphomas and contrast with the higher activity level reported with the second generation immunomodulatory agent, lenalidomide."],"offsets":[[157,1338]]}],"entities":[{"id":"9032","type":"Chemical","text":["Thalidomide"],"offsets":[[0,11]],"normalized":[{"db_name":"MESH","db_id":"D013792"}]},{"id":"9033","type":"Disease","text":["non-Hodgkin lymphomas"],"offsets":[[81,102]],"normalized":[{"db_name":"MESH","db_id":"D008228"}]},{"id":"9034","type":"Disease","text":["Cancer"],"offsets":[[128,134]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"9035","type":"Disease","text":["Leukemia"],"offsets":[[139,147]],"normalized":[{"db_name":"MESH","db_id":"D007938"}]},{"id":"9036","type":"Chemical","text":["Thalidomide"],"offsets":[[157,168]],"normalized":[{"db_name":"MESH","db_id":"D013792"}]},{"id":"9037","type":"Disease","text":["multiple myeloma"],"offsets":[[228,244]],"normalized":[{"db_name":"MESH","db_id":"D009101"}]},{"id":"9038","type":"Disease","text":["mantle cell lymphoma"],"offsets":[[246,266]],"normalized":[{"db_name":"MESH","db_id":"D020522"}]},{"id":"9039","type":"Disease","text":["lymphoplasmacytic lymphoma"],"offsets":[[271,297]],"normalized":[{"db_name":"MESH","db_id":"D008223"}]},{"id":"9040","type":"Disease","text":["tumour"],"offsets":[[352,358]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"9041","type":"Disease","text":["lymphomas"],"offsets":[[516,525]],"normalized":[{"db_name":"MESH","db_id":"D008223"}]},{"id":"9042","type":"Chemical","text":["thalidomide"],"offsets":[[535,546]],"normalized":[{"db_name":"MESH","db_id":"D013792"}]},{"id":"9043","type":"Disease","text":["myelosuppression"],"offsets":[[971,987]],"normalized":[{"db_name":"MESH","db_id":"D001855"}]},{"id":"9044","type":"Disease","text":["fatigue"],"offsets":[[989,996]],"normalized":[{"db_name":"MESH","db_id":"D005221"}]},{"id":"9045","type":"Disease","text":["somnolence"],"offsets":[[998,1008]],"normalized":[{"db_name":"MESH","db_id":"D006970"}]},{"id":"9046","type":"Disease","text":["depressed mood"],"offsets":[[1009,1023]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"9047","type":"Disease","text":["neuropathy"],"offsets":[[1025,1035]],"normalized":[{"db_name":"MESH","db_id":"D009422"}]},{"id":"9048","type":"Disease","text":["dyspnea"],"offsets":[[1040,1047]],"normalized":[{"db_name":"MESH","db_id":"D004417"}]},{"id":"9049","type":"Disease","text":["thromboembolic"],"offsets":[[1087,1101]],"normalized":[{"db_name":"MESH","db_id":"D013923"}]},{"id":"9050","type":"Chemical","text":["thalidomide"],"offsets":[[1187,1198]],"normalized":[{"db_name":"MESH","db_id":"D013792"}]},{"id":"9051","type":"Disease","text":["lymphomas"],"offsets":[[1211,1220]],"normalized":[{"db_name":"MESH","db_id":"D008223"}]},{"id":"9052","type":"Chemical","text":["lenalidomide"],"offsets":[[1325,1337]],"normalized":[{"db_name":"MESH","db_id":"C467567"}]}],"events":[],"coreferences":[],"relations":[{"id":"9053","type":"CID","arg1_id":"9032","arg2_id":"9049","normalized":[]},{"id":"9054","type":"CID","arg1_id":"9036","arg2_id":"9049","normalized":[]},{"id":"9055","type":"CID","arg1_id":"9042","arg2_id":"9049","normalized":[]},{"id":"9056","type":"CID","arg1_id":"9050","arg2_id":"9049","normalized":[]}]}
{"id":"9057","document_id":"18996674","passages":[{"id":"9058","type":"title","text":["Intracavernous epinephrine: a minimally invasive treatment for priapism in the emergency department."],"offsets":[[0,100]]},{"id":"9059","type":"abstract","text":["Priapism is the prolonged erection of the penis in the absence of sexual arousal. A 45-year-old man, an admitted frequent cocaine user, presented to the Emergency Department (ED) on two separate occasions with a history of priapism after cocaine use. The management options in the ED, as exemplified by four individual case reports, in particular the use of a minimally invasive method of intracorporal epinephrine instillation, are discussed."],"offsets":[[101,544]]}],"entities":[{"id":"9060","type":"Chemical","text":["epinephrine"],"offsets":[[15,26]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"9061","type":"Disease","text":["priapism"],"offsets":[[63,71]],"normalized":[{"db_name":"MESH","db_id":"D011317"}]},{"id":"9062","type":"Disease","text":["Priapism"],"offsets":[[101,109]],"normalized":[{"db_name":"MESH","db_id":"D011317"}]},{"id":"9063","type":"Chemical","text":["cocaine"],"offsets":[[223,230]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"9064","type":"Disease","text":["priapism"],"offsets":[[324,332]],"normalized":[{"db_name":"MESH","db_id":"D011317"}]},{"id":"9065","type":"Chemical","text":["cocaine"],"offsets":[[339,346]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"9066","type":"Chemical","text":["epinephrine"],"offsets":[[504,515]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]}],"events":[],"coreferences":[],"relations":[{"id":"9067","type":"CID","arg1_id":"9063","arg2_id":"9061","normalized":[]},{"id":"9068","type":"CID","arg1_id":"9063","arg2_id":"9062","normalized":[]},{"id":"9069","type":"CID","arg1_id":"9063","arg2_id":"9064","normalized":[]},{"id":"9070","type":"CID","arg1_id":"9065","arg2_id":"9061","normalized":[]},{"id":"9071","type":"CID","arg1_id":"9065","arg2_id":"9062","normalized":[]},{"id":"9072","type":"CID","arg1_id":"9065","arg2_id":"9064","normalized":[]}]}
{"id":"9073","document_id":"19058010","passages":[{"id":"9074","type":"title","text":["Effect of green tea and vitamin E combination in isoproterenol induced myocardial infarction in rats."],"offsets":[[0,101]]},{"id":"9075","type":"abstract","text":["The present study was aimed to investigate the combined effects of green tea and vitamin E on heart weight, body weight, serum marker enzymes, lipid peroxidation, endogenous antioxidants and membrane bound ATPases in isoproterenol (ISO)-induced myocardial infarction in rats. Adult male albino rats, treated with ISO (200 mg\/kg, s.c.) for 2 days at an interval of 24 h caused a significant (P<0.05) elevation of heart weight, serum marker enzymes, lipid peroxidation and Ca+2 ATPase level whereas there was a significant (P<0.05) decrease in body weight, endogenous antioxidants, Na+\/ K+ ATPase and Mg+2 ATPase levels. Administration of green tea (100 mg\/kg\/day, p.o.) and vitamin E (100 mg\/kg\/day, p.o.) together for 30 consecutive days and challenged with ISO on the day 29th and 30th, showed a significant (P<0.05) decrease in heart weight, serum marker enzymes, lipid peroxidation, Ca+2 ATPase and a significant increase in the body weight, endogenous antioxidants, Na+\/K+ ATPase and Mg+2 ATPase when compared with ISO treated group and green tea or vitamin E alone treated groups. These findings indicate the synergistic protective effect of green tea and vitamin E during ISO induced myocardial infarction in rats."],"offsets":[[102,1322]]}],"entities":[{"id":"9076","type":"Chemical","text":["green tea"],"offsets":[[10,19]],"normalized":[{"db_name":"MESH","db_id":"D010936"}]},{"id":"9077","type":"Chemical","text":["vitamin E"],"offsets":[[24,33]],"normalized":[{"db_name":"MESH","db_id":"D014810"}]},{"id":"9078","type":"Chemical","text":["isoproterenol"],"offsets":[[49,62]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"9079","type":"Disease","text":["myocardial infarction"],"offsets":[[71,92]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"9080","type":"Chemical","text":["green tea"],"offsets":[[169,178]],"normalized":[{"db_name":"MESH","db_id":"D010936"}]},{"id":"9081","type":"Chemical","text":["vitamin 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{"id":"9125","document_id":"19581773","passages":[{"id":"9126","type":"title","text":["Development of ocular myasthenia during pegylated interferon and ribavirin treatment for chronic hepatitis C."],"offsets":[[0,109]]},{"id":"9127","type":"abstract","text":["A 63-year-old male experienced sudden diplopia after 9 weeks of administration of pegylated interferon (IFN) alpha-2b and ribavirin for chronic hepatitis C (CHC). Ophthalmologic examinations showed ptosis on the right upper lid and restricted right eye movement without any other neurological signs. A brain imaging study and repetitive nerve stimulation test indicated no abnormality. The acetylcholine receptor antibody titer and response to acetylcholinesterase inhibitors were negative, and the results of thyroid function tests were normal. The patient's ophthalmological symptoms improved rapidly 3 weeks after discontinuation of pegylated IFN alpha-2b and ribavirin. The ocular myasthenia associated with combination therapy of pegylated IFN alpha-2b and ribavirin for CHC is very rarely reported; therefore, we present this case with a review of the various eye complications of IFN therapy."],"offsets":[[110,1009]]}],"entities":[{"id":"9128","type":"Disease","text":["ocular myasthenia"],"offsets":[[15,32]],"normalized":[{"db_name":"MESH","db_id":"D009157"}]},{"id":"9129","type":"Chemical","text":["pegylated interferon"],"offsets":[[40,60]],"normalized":[{"db_name":"MESH","db_id":"C417083"}]},{"id":"9130","type":"Chemical","text":["ribavirin"],"offsets":[[65,74]],"normalized":[{"db_name":"MESH","db_id":"D012254"}]},{"id":"9131","type":"Disease","text":["chronic hepatitis C"],"offsets":[[89,108]],"normalized":[{"db_name":"MESH","db_id":"D019698"}]},{"id":"9132","type":"Disease","text":["diplopia"],"offsets":[[148,156]],"normalized":[{"db_name":"MESH","db_id":"D004172"}]},{"id":"9133","type":"Chemical","text":["pegylated interferon (IFN) alpha-2b"],"offsets":[[192,227]],"normalized":[{"db_name":"MESH","db_id":"C417083"}]},{"id":"9134","type":"Chemical","text":["ribavirin"],"offsets":[[232,241]],"normalized":[{"db_name":"MESH","db_id":"D012254"}]},{"id":"9135","type":"Disease","text":["chronic hepatitis C"],"offsets":[[246,265]],"normalized":[{"db_name":"MESH","db_id":"D019698"}]},{"id":"9136","type":"Disease","text":["CHC"],"offsets":[[267,270]],"normalized":[{"db_name":"MESH","db_id":"D019698"}]},{"id":"9137","type":"Disease","text":["ptosis on the right upper lid"],"offsets":[[308,337]],"normalized":[{"db_name":"MESH","db_id":"D001763"}]},{"id":"9138","type":"Disease","text":["restricted right eye movement"],"offsets":[[342,371]],"normalized":[{"db_name":"MESH","db_id":"D015835"}]},{"id":"9139","type":"Chemical","text":["acetylcholine"],"offsets":[[500,513]],"normalized":[{"db_name":"MESH","db_id":"D000109"}]},{"id":"9140","type":"Chemical","text":["pegylated IFN alpha-2b"],"offsets":[[746,768]],"normalized":[{"db_name":"MESH","db_id":"C417083"}]},{"id":"9141","type":"Chemical","text":["ribavirin"],"offsets":[[773,782]],"normalized":[{"db_name":"MESH","db_id":"D012254"}]},{"id":"9142","type":"Disease","text":["ocular myasthenia"],"offsets":[[788,805]],"normalized":[{"db_name":"MESH","db_id":"D009157"}]},{"id":"9143","type":"Chemical","text":["pegylated IFN alpha-2b"],"offsets":[[845,867]],"normalized":[{"db_name":"MESH","db_id":"C417083"}]},{"id":"9144","type":"Chemical","text":["ribavirin"],"offsets":[[872,881]],"normalized":[{"db_name":"MESH","db_id":"D012254"}]},{"id":"9145","type":"Disease","text":["CHC"],"offsets":[[886,889]],"normalized":[{"db_name":"MESH","db_id":"D019698"}]},{"id":"9146","type":"Chemical","text":["IFN"],"offsets":[[997,1000]],"normalized":[{"db_name":"MESH","db_id":"C417083"}]}],"events":[],"coreferences":[],"relations":[{"id":"9147","type":"CID","arg1_id":"9130","arg2_id":"9128","normalized":[]},{"id":"9148","type":"CID","arg1_id":"9130","arg2_id":"9142","normalized":[]},{"id":"9149","type":"CID","arg1_id":"9134","arg2_id":"9128","normalized":[]},{"id":"9150","type":"CID","arg1_id":"9134","arg2_id":"9142","normalized":[]},{"id":"9151","type":"CID","arg1_id":"9141","arg2_id":"9128","normalized":[]},{"id":"9152","type":"CID","arg1_id":"9141","arg2_id":"9142","normalized":[]},{"id":"9153","type":"CID","arg1_id":"9144","arg2_id":"9128","normalized":[]},{"id":"9154","type":"CID","arg1_id":"9144","arg2_id":"9142","normalized":[]},{"id":"9155","type":"CID","arg1_id":"9129","arg2_id":"9137","normalized":[]},{"id":"9156","type":"CID","arg1_id":"9133","arg2_id":"9137","normalized":[]},{"id":"9157","type":"CID","arg1_id":"9140","arg2_id":"9137","normalized":[]},{"id":"9158","type":"CID","arg1_id":"9143","arg2_id":"9137","normalized":[]},{"id":"9159","type":"CID","arg1_id":"9146","arg2_id":"9137","normalized":[]},{"id":"9160","type":"CID","arg1_id":"9130","arg2_id":"9137","normalized":[]},{"id":"9161","type":"CID","arg1_id":"9134","arg2_id":"9137","normalized":[]},{"id":"9162","type":"CID","arg1_id":"9141","arg2_id":"9137","normalized":[]},{"id":"9163","type":"CID","arg1_id":"9144","arg2_id":"9137","normalized":[]},{"id":"9164","type":"CID","arg1_id":"9129","arg2_id":"9138","normalized":[]},{"id":"9165","type":"CID","arg1_id":"9133","arg2_id":"9138","normalized":[]},{"id":"9166","type":"CID","arg1_id":"9140","arg2_id":"9138","normalized":[]},{"id":"9167","type":"CID","arg1_id":"9143","arg2_id":"9138","normalized":[]},{"id":"9168","type":"CID","arg1_id":"9146","arg2_id":"9138","normalized":[]},{"id":"9169","type":"CID","arg1_id":"9129","arg2_id":"9128","normalized":[]},{"id":"9170","type":"CID","arg1_id":"9129","arg2_id":"9142","normalized":[]},{"id":"9171","type":"CID","arg1_id":"9133","arg2_id":"9128","normalized":[]},{"id":"9172","type":"CID","arg1_id":"9133","arg2_id":"9142","normalized":[]},{"id":"9173","type":"CID","arg1_id":"9140","arg2_id":"9128","normalized":[]},{"id":"9174","type":"CID","arg1_id":"9140","arg2_id":"9142","normalized":[]},{"id":"9175","type":"CID","arg1_id":"9143","arg2_id":"9128","normalized":[]},{"id":"9176","type":"CID","arg1_id":"9143","arg2_id":"9142","normalized":[]},{"id":"9177","type":"CID","arg1_id":"9146","arg2_id":"9128","normalized":[]},{"id":"9178","type":"CID","arg1_id":"9146","arg2_id":"9142","normalized":[]},{"id":"9179","type":"CID","arg1_id":"9130","arg2_id":"9138","normalized":[]},{"id":"9180","type":"CID","arg1_id":"9134","arg2_id":"9138","normalized":[]},{"id":"9181","type":"CID","arg1_id":"9141","arg2_id":"9138","normalized":[]},{"id":"9182","type":"CID","arg1_id":"9144","arg2_id":"9138","normalized":[]}]}
{"id":"9183","document_id":"19759529","passages":[{"id":"9184","type":"title","text":["The glycine transporter-1 inhibitor SSR103800 displays a selective and specific antipsychotic-like profile in normal and transgenic mice."],"offsets":[[0,137]]},{"id":"9185","type":"abstract","text":["Schizophrenia has been initially associated with dysfunction in dopamine neurotransmission. However, the observation that antagonists of the glutamate N-methyl-D-aspartate (NMDA) receptor produce schizophrenic-like symptoms in humans has led to the idea of a dysfunctioning of the glutamatergic system via its NMDA receptor. As a result, there is a growing interest in the development of pharmacological agents with potential antipsychotic properties that enhance the activity of the glutamatergic system via a modulation of the NMDA receptor. Among them are glycine transporter-1 (GlyT1) inhibitors such as SSR103800, which indirectly enhance NMDA receptor function by increasing the glycine (a co-agonist for the NMDA receptor) levels in the synapse. This study aimed at investigating the potential antipsychotic-like properties of SSR103800, with a particular focus on models of hyperactivity, involving either drug challenge (ie, amphetamine and MK-801) or transgenic mice (ie, NMDA Nr1(neo-\/-) and DAT(-\/-)). Results showed that SSR103800 (10-30 mg\/kg p.o.) blocked hyperactivity induced by the non-competitive NMDA receptor antagonist, MK-801 and partially reversed spontaneous hyperactivity of NMDA Nr1(neo-\/-) mice. In contrast, SSR103800 failed to affect hyperactivity induced by amphetamine or naturally observed in dopamine transporter (DAT(-\/-)) knockout mice (10-30 mg\/kg p.o.). Importantly, both classical (haloperidol) and atypical (olanzapine, clozapine and aripiprazole) antipsychotics were effective in all these models of hyperactivity. However, unlike these latter, SSR103800 did not produce catalepsy (retention on the bar test) up to 30 mg\/kg p.o. Together these findings show that the GlyT1 inhibitor, SSR103800, produces antipsychotic-like effects, which differ from those observed with compounds primarily targeting the dopaminergic system, and has a reduced side-effect potential as compared with these latter drugs."],"offsets":[[138,2080]]}],"entities":[{"id":"9186","type":"Chemical","text":["glycine"],"offsets":[[4,11]],"normalized":[{"db_name":"MESH","db_id":"D005998"}]},{"id":"9187","type":"Chemical","text":["SSR103800"],"offsets":[[36,45]],"normalized":[]},{"id":"9188","type":"Disease","text":["Schizophrenia"],"offsets":[[138,151]],"normalized":[{"db_name":"MESH","db_id":"D012559"}]},{"id":"9189","type":"Chemical","text":["dopamine"],"offsets":[[202,210]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"9190","type":"Chemical","text":["glutamate"],"offsets":[[279,288]],"normalized":[{"db_name":"MESH","db_id":"D018698"}]},{"id":"9191","type":"Chemical","text":["N-methyl-D-aspartate"],"offsets":[[289,309]],"normalized":[{"db_name":"MESH","db_id":"D016202"}]},{"id":"9192","type":"Chemical","text":["NMDA"],"offsets":[[311,315]],"normalized":[{"db_name":"MESH","db_id":"D016202"}]},{"id":"9193","type":"Disease","text":["schizophrenic"],"offsets":[[334,347]],"normalized":[{"db_name":"MESH","db_id":"D012559"}]},{"id":"9194","type":"Chemical","text":["NMDA"],"offsets":[[448,452]],"normalized":[{"db_name":"MESH","db_id":"D016202"}]},{"id":"9195","type":"Chemical","text":["NMDA"],"offsets":[[667,671]],"normalized":[{"db_name":"MESH","db_id":"D016202"}]},{"id":"9196","type":"Chemical","text":["glycine"],"offsets":[[697,704]],"normalized":[{"db_name":"MESH","db_id":"D005998"}]},{"id":"9197","type":"Chemical","text":["SSR103800"],"offsets":[[746,755]],"normalized":[]},{"id":"9198","type":"Chemical","text":["NMDA"],"offsets":[[782,786]],"normalized":[{"db_name":"MESH","db_id":"D016202"}]},{"id":"9199","type":"Chemical","text":["glycine"],"offsets":[[823,830]],"normalized":[{"db_name":"MESH","db_id":"D005998"}]},{"id":"9200","type":"Chemical","text":["NMDA"],"offsets":[[853,857]],"normalized":[{"db_name":"MESH","db_id":"D016202"}]},{"id":"9201","type":"Chemical","text":["SSR103800"],"offsets":[[972,981]],"normalized":[]},{"id":"9202","type":"Disease","text":["hyperactivity"],"offsets":[[1020,1033]],"normalized":[{"db_name":"MESH","db_id":"D006948"}]},{"id":"9203","type":"Chemical","text":["amphetamine"],"offsets":[[1072,1083]],"normalized":[{"db_name":"MESH","db_id":"D000661"}]},{"id":"9204","type":"Chemical","text":["MK-801"],"offsets":[[1088,1094]],"normalized":[{"db_name":"MESH","db_id":"D016291"}]},{"id":"9205","type":"Chemical","text":["NMDA"],"offsets":[[1120,1124]],"normalized":[{"db_name":"MESH","db_id":"D016202"}]},{"id":"9206","type":"Chemical","text":["SSR103800"],"offsets":[[1172,1181]],"normalized":[]},{"id":"9207","type":"Disease","text":["hyperactivity"],"offsets":[[1209,1222]],"normalized":[{"db_name":"MESH","db_id":"D006948"}]},{"id":"9208","type":"Chemical","text":["NMDA"],"offsets":[[1254,1258]],"normalized":[{"db_name":"MESH","db_id":"D016202"}]},{"id":"9209","type":"Chemical","text":["MK-801"],"offsets":[[1280,1286]],"normalized":[{"db_name":"MESH","db_id":"D016291"}]},{"id":"9210","type":"Disease","text":["hyperactivity"],"offsets":[[1322,1335]],"normalized":[{"db_name":"MESH","db_id":"D006948"}]},{"id":"9211","type":"Chemical","text":["NMDA"],"offsets":[[1339,1343]],"normalized":[{"db_name":"MESH","db_id":"D016202"}]},{"id":"9212","type":"Chemical","text":["SSR103800"],"offsets":[[1375,1384]],"normalized":[]},{"id":"9213","type":"Disease","text":["hyperactivity"],"offsets":[[1402,1415]],"normalized":[{"db_name":"MESH","db_id":"D006948"}]},{"id":"9214","type":"Chemical","text":["amphetamine"],"offsets":[[1427,1438]],"normalized":[{"db_name":"MESH","db_id":"D000661"}]},{"id":"9215","type":"Chemical","text":["dopamine"],"offsets":[[1464,1472]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"9216","type":"Chemical","text":["haloperidol"],"offsets":[[1559,1570]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"9217","type":"Chemical","text":["olanzapine"],"offsets":[[1586,1596]],"normalized":[{"db_name":"MESH","db_id":"C076029"}]},{"id":"9218","type":"Chemical","text":["clozapine"],"offsets":[[1598,1607]],"normalized":[{"db_name":"MESH","db_id":"D003024"}]},{"id":"9219","type":"Chemical","text":["aripiprazole"],"offsets":[[1612,1624]],"normalized":[{"db_name":"MESH","db_id":"C094645"}]},{"id":"9220","type":"Disease","text":["hyperactivity"],"offsets":[[1679,1692]],"normalized":[{"db_name":"MESH","db_id":"D006948"}]},{"id":"9221","type":"Chemical","text":["SSR103800"],"offsets":[[1724,1733]],"normalized":[]},{"id":"9222","type":"Disease","text":["catalepsy"],"offsets":[[1750,1759]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"9223","type":"Chemical","text":["SSR103800"],"offsets":[[1863,1872]],"normalized":[]}],"events":[],"coreferences":[],"relations":[{"id":"9224","type":"CID","arg1_id":"9219","arg2_id":"9222","normalized":[]},{"id":"9225","type":"CID","arg1_id":"9216","arg2_id":"9222","normalized":[]},{"id":"9226","type":"CID","arg1_id":"9217","arg2_id":"9222","normalized":[]},{"id":"9227","type":"CID","arg1_id":"9204","arg2_id":"9202","normalized":[]},{"id":"9228","type":"CID","arg1_id":"9204","arg2_id":"9207","normalized":[]},{"id":"9229","type":"CID","arg1_id":"9204","arg2_id":"9210","normalized":[]},{"id":"9230","type":"CID","arg1_id":"9204","arg2_id":"9213","normalized":[]},{"id":"9231","type":"CID","arg1_id":"9204","arg2_id":"9220","normalized":[]},{"id":"9232","type":"CID","arg1_id":"9209","arg2_id":"9202","normalized":[]},{"id":"9233","type":"CID","arg1_id":"9209","arg2_id":"9207","normalized":[]},{"id":"9234","type":"CID","arg1_id":"9209","arg2_id":"9210","normalized":[]},{"id":"9235","type":"CID","arg1_id":"9209","arg2_id":"9213","normalized":[]},{"id":"9236","type":"CID","arg1_id":"9209","arg2_id":"9220","normalized":[]},{"id":"9237","type":"CID","arg1_id":"9203","arg2_id":"9202","normalized":[]},{"id":"9238","type":"CID","arg1_id":"9203","arg2_id":"9207","normalized":[]},{"id":"9239","type":"CID","arg1_id":"9203","arg2_id":"9210","normalized":[]},{"id":"9240","type":"CID","arg1_id":"9203","arg2_id":"9213","normalized":[]},{"id":"9241","type":"CID","arg1_id":"9203","arg2_id":"9220","normalized":[]},{"id":"9242","type":"CID","arg1_id":"9214","arg2_id":"9202","normalized":[]},{"id":"9243","type":"CID","arg1_id":"9214","arg2_id":"9207","normalized":[]},{"id":"9244","type":"CID","arg1_id":"9214","arg2_id":"9210","normalized":[]},{"id":"9245","type":"CID","arg1_id":"9214","arg2_id":"9213","normalized":[]},{"id":"9246","type":"CID","arg1_id":"9214","arg2_id":"9220","normalized":[]},{"id":"9247","type":"CID","arg1_id":"9218","arg2_id":"9222","normalized":[]}]}
{"id":"9248","document_id":"19957053","passages":[{"id":"9249","type":"title","text":["Phenylephrine but not ephedrine reduces frontal lobe oxygenation following anesthesia-induced hypotension."],"offsets":[[0,106]]},{"id":"9250","type":"abstract","text":["BACKGROUND: Vasopressor agents are used to correct anesthesia-induced hypotension. We describe the effect of phenylephrine and ephedrine on frontal lobe oxygenation (S(c)O(2)) following anesthesia-induced hypotension. METHODS: Following induction of anesthesia by fentanyl (0.15 mg kg(-1)) and propofol (2.0 mg kg(-1)), 13 patients received phenylephrine (0.1 mg iv) and 12 patients received ephedrine (10 mg iv) to restore mean arterial pressure (MAP). Heart rate (HR), MAP, stroke volume (SV), cardiac output (CO), and frontal lobe oxygenation (S(c)O(2)) were registered. RESULTS: Induction of anesthesia was followed by a decrease in MAP, HR, SV, and CO concomitant with an elevation in S(c)O(2). After administration of phenylephrine, MAP increased (51 +\/- 12 to 81 +\/- 13 mmHg; P < 0.001; mean +\/- SD). However, a 14% (from 70 +\/- 8% to 60 +\/- 7%) reduction in S(c)O(2) (P < 0.05) followed with no change in CO (3.7 +\/- 1.1 to 3.4 +\/- 0.9 l min(-1)). The administration of ephedrine led to a similar increase in MAP (53 +\/- 9 to 79 +\/- 8 mmHg; P < 0.001), restored CO (3.2 +\/- 1.2 to 5.0 +\/- 1.3 l min(-1)), and preserved S(c)O(2). CONCLUSIONS: The utilization of phenylephrine to correct hypotension induced by anesthesia has a negative impact on S(c)O(2) while ephedrine maintains frontal lobe oxygenation potentially related to an increase in CO."],"offsets":[[107,1461]]}],"entities":[{"id":"9251","type":"Chemical","text":["Phenylephrine"],"offsets":[[0,13]],"normalized":[{"db_name":"MESH","db_id":"D010656"}]},{"id":"9252","type":"Chemical","text":["ephedrine"],"offsets":[[22,31]],"normalized":[{"db_name":"MESH","db_id":"D004809"}]},{"id":"9253","type":"Disease","text":["reduces frontal lobe oxygenation"],"offsets":[[32,64]],"normalized":[{"db_name":"MESH","db_id":"D002534"}]},{"id":"9254","type":"Disease","text":["hypotension"],"offsets":[[94,105]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"9255","type":"Disease","text":["hypotension"],"offsets":[[177,188]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"9256","type":"Chemical","text":["phenylephrine"],"offsets":[[216,229]],"normalized":[{"db_name":"MESH","db_id":"D010656"}]},{"id":"9257","type":"Chemical","text":["ephedrine"],"offsets":[[234,243]],"normalized":[{"db_name":"MESH","db_id":"D004809"}]},{"id":"9258","type":"Disease","text":["hypotension"],"offsets":[[312,323]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"9259","type":"Chemical","text":["fentanyl"],"offsets":[[371,379]],"normalized":[{"db_name":"MESH","db_id":"D005283"}]},{"id":"9260","type":"Chemical","text":["propofol"],"offsets":[[401,409]],"normalized":[{"db_name":"MESH","db_id":"D015742"}]},{"id":"9261","type":"Chemical","text":["phenylephrine"],"offsets":[[448,461]],"normalized":[{"db_name":"MESH","db_id":"D010656"}]},{"id":"9262","type":"Chemical","text":["ephedrine"],"offsets":[[499,508]],"normalized":[{"db_name":"MESH","db_id":"D004809"}]},{"id":"9263","type":"Disease","text":["stroke"],"offsets":[[583,589]],"normalized":[{"db_name":"MESH","db_id":"D020521"}]},{"id":"9264","type":"Disease","text":["a decrease in MAP, HR, SV, and CO"],"offsets":[[730,763]],"normalized":[{"db_name":"MESH","db_id":"D007022"},{"db_name":"MESH","db_id":"D002303"}]},{"id":"9265","type":"Disease","text":["a decrease in MAP"],"offsets":[[730,747]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"9266","type":"Disease","text":["a decrease in","CO"],"offsets":[[730,743],[761,763]],"normalized":[{"db_name":"MESH","db_id":"D002303"}]},{"id":"9267","type":"Chemical","text":["phenylephrine"],"offsets":[[831,844]],"normalized":[{"db_name":"MESH","db_id":"D010656"}]},{"id":"9268","type":"Chemical","text":["ephedrine"],"offsets":[[1085,1094]],"normalized":[{"db_name":"MESH","db_id":"D004809"}]},{"id":"9269","type":"Chemical","text":["phenylephrine"],"offsets":[[1276,1289]],"normalized":[{"db_name":"MESH","db_id":"D010656"}]},{"id":"9270","type":"Disease","text":["hypotension"],"offsets":[[1301,1312]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"9271","type":"Chemical","text":["ephedrine"],"offsets":[[1375,1384]],"normalized":[{"db_name":"MESH","db_id":"D004809"}]}],"events":[],"coreferences":[],"relations":[{"id":"9272","type":"CID","arg1_id":"9259","arg2_id":"9254","normalized":[]},{"id":"9273","type":"CID","arg1_id":"9259","arg2_id":"9255","normalized":[]},{"id":"9274","type":"CID","arg1_id":"9259","arg2_id":"9258","normalized":[]},{"id":"9275","type":"CID","arg1_id":"9259","arg2_id":"9264","normalized":[]},{"id":"9276","type":"CID","arg1_id":"9259","arg2_id":"9265","normalized":[]},{"id":"9277","type":"CID","arg1_id":"9259","arg2_id":"9270","normalized":[]},{"id":"9278","type":"CID","arg1_id":"9259","arg2_id":"9264","normalized":[]},{"id":"9279","type":"CID","arg1_id":"9259","arg2_id":"9266","normalized":[]},{"id":"9280","type":"CID","arg1_id":"9260","arg2_id":"9254","normalized":[]},{"id":"9281","type":"CID","arg1_id":"9260","arg2_id":"9255","normalized":[]},{"id":"9282","type":"CID","arg1_id":"9260","arg2_id":"9258","normalized":[]},{"id":"9283","type":"CID","arg1_id":"9260","arg2_id":"9264","normalized":[]},{"id":"9284","type":"CID","arg1_id":"9260","arg2_id":"9265","normalized":[]},{"id":"9285","type":"CID","arg1_id":"9260","arg2_id":"9270","normalized":[]},{"id":"9286","type":"CID","arg1_id":"9260","arg2_id":"9264","normalized":[]},{"id":"9287","type":"CID","arg1_id":"9260","arg2_id":"9266","normalized":[]},{"id":"9288","type":"CID","arg1_id":"9251","arg2_id":"9253","normalized":[]},{"id":"9289","type":"CID","arg1_id":"9256","arg2_id":"9253","normalized":[]},{"id":"9290","type":"CID","arg1_id":"9261","arg2_id":"9253","normalized":[]},{"id":"9291","type":"CID","arg1_id":"9267","arg2_id":"9253","normalized":[]},{"id":"9292","type":"CID","arg1_id":"9269","arg2_id":"9253","normalized":[]}]}
{"id":"9293","document_id":"20619828","passages":[{"id":"9294","type":"title","text":["A novel, multiple symptom model of obsessive-compulsive-like behaviors in animals."],"offsets":[[0,82]]},{"id":"9295","type":"abstract","text":["BACKGROUND: Current animal models of obsessive-compulsive disorder (OCD) typically involve acute, drug-induced symptom provocation or a genetic association with stereotypies or anxiety. None of these current models demonstrate multiple OCD-like behaviors. METHODS: Neonatal rats were treated with the tricyclic antidepressant clomipramine or vehicle between days 9 and 16 twice daily and behaviorally tested in adulthood. RESULTS: Clomipramine exposure in immature rats produced significant behavioral and biochemical changes that include enhanced anxiety (elevated plus maze and marble burying), behavioral inflexibility (perseveration in the spontaneous alternation task and impaired reversal learning), working memory impairment (e.g., win-shift paradigm), hoarding, and corticostriatal dysfunction. Dopamine D2 receptors were elevated in the striatum, whereas serotonin 2C, but not serotonin 1A, receptors were elevated in the orbital frontal cortex. CONCLUSIONS: This is the first demonstration of multiple symptoms consistent with an OCD-like profile in animals. Moreover, these behaviors are accompanied by biochemical changes in brain regions previously identified as relevant to OCD. This novel model of OCD demonstrates that drug exposure during a sensitive period can program disease-like systems permanently, which could have implications for current and future therapeutic strategies for this and other psychiatric disorders."],"offsets":[[83,1521]]}],"entities":[{"id":"9296","type":"Disease","text":["obsessive-compulsive-like behaviors"],"offsets":[[35,70]],"normalized":[{"db_name":"MESH","db_id":"D009771"}]},{"id":"9297","type":"Disease","text":["obsessive-compulsive disorder"],"offsets":[[120,149]],"normalized":[{"db_name":"MESH","db_id":"D009771"}]},{"id":"9298","type":"Disease","text":["OCD"],"offsets":[[151,154]],"normalized":[{"db_name":"MESH","db_id":"D009771"}]},{"id":"9299","type":"Disease","text":["anxiety"],"offsets":[[260,267]],"normalized":[{"db_name":"MESH","db_id":"D001008"}]},{"id":"9300","type":"Disease","text":["OCD"],"offsets":[[319,322]],"normalized":[{"db_name":"MESH","db_id":"D009771"}]},{"id":"9301","type":"Chemical","text":["antidepressant"],"offsets":[[394,408]],"normalized":[{"db_name":"MESH","db_id":"D000928"}]},{"id":"9302","type":"Chemical","text":["clomipramine"],"offsets":[[409,421]],"normalized":[{"db_name":"MESH","db_id":"D002997"}]},{"id":"9303","type":"Chemical","text":["Clomipramine"],"offsets":[[514,526]],"normalized":[{"db_name":"MESH","db_id":"D002997"}]},{"id":"9304","type":"Disease","text":["anxiety"],"offsets":[[631,638]],"normalized":[{"db_name":"MESH","db_id":"D001008"}]},{"id":"9305","type":"Disease","text":["behavioral inflexibility"],"offsets":[[680,704]],"normalized":[]},{"id":"9306","type":"Disease","text":["memory impairment"],"offsets":[[797,814]],"normalized":[{"db_name":"MESH","db_id":"D008569"}]},{"id":"9307","type":"Disease","text":["hoarding"],"offsets":[[843,851]],"normalized":[{"db_name":"MESH","db_id":"D060845"}]},{"id":"9308","type":"Disease","text":["corticostriatal dysfunction"],"offsets":[[857,884]],"normalized":[]},{"id":"9309","type":"Chemical","text":["Dopamine"],"offsets":[[886,894]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"9310","type":"Chemical","text":["serotonin"],"offsets":[[947,956]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"9311","type":"Chemical","text":["serotonin"],"offsets":[[969,978]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"9312","type":"Disease","text":["OCD"],"offsets":[[1123,1126]],"normalized":[{"db_name":"MESH","db_id":"D009771"}]},{"id":"9313","type":"Disease","text":["OCD"],"offsets":[[1271,1274]],"normalized":[{"db_name":"MESH","db_id":"D009771"}]},{"id":"9314","type":"Disease","text":["OCD"],"offsets":[[1296,1299]],"normalized":[{"db_name":"MESH","db_id":"D009771"}]},{"id":"9315","type":"Disease","text":["psychiatric disorders"],"offsets":[[1499,1520]],"normalized":[{"db_name":"MESH","db_id":"D001523"}]}],"events":[],"coreferences":[],"relations":[{"id":"9316","type":"CID","arg1_id":"9302","arg2_id":"9306","normalized":[]},{"id":"9317","type":"CID","arg1_id":"9303","arg2_id":"9306","normalized":[]},{"id":"9318","type":"CID","arg1_id":"9302","arg2_id":"9299","normalized":[]},{"id":"9319","type":"CID","arg1_id":"9302","arg2_id":"9304","normalized":[]},{"id":"9320","type":"CID","arg1_id":"9303","arg2_id":"9299","normalized":[]},{"id":"9321","type":"CID","arg1_id":"9303","arg2_id":"9304","normalized":[]},{"id":"9322","type":"CID","arg1_id":"9302","arg2_id":"9307","normalized":[]},{"id":"9323","type":"CID","arg1_id":"9303","arg2_id":"9307","normalized":[]}]}
{"id":"9324","document_id":"891050","passages":[{"id":"9325","type":"title","text":["Late recovery of renal function in a woman with the hemolytic uremic syndrome."],"offsets":[[0,78]]},{"id":"9326","type":"abstract","text":["A case is reported of the hemolytic uremic syndrome (HUS) in a woman taking oral contraceptives. She was treated with heparin, dipyridamole and hemodialysis; and after more than three months, her urinary output rose above 500 ml; and six months after the onset of anuria, dialysis treatment was stopped. This case emphasizes the possibility that HUS in adults is not invariably irreversible and that, despite prolonged oliguria, recovery of renal function can be obtained. Therefore, in adult patients affected by HUS, dialysis should not be discontinued prematurely; moreover, bilateral nephrectomy, for treatment of severe hypertension and microangiopathic hemolytic anemia, should be performed with caution."],"offsets":[[79,789]]}],"entities":[{"id":"9327","type":"Disease","text":["hemolytic uremic syndrome"],"offsets":[[52,77]],"normalized":[{"db_name":"MESH","db_id":"D006463"}]},{"id":"9328","type":"Disease","text":["hemolytic uremic syndrome"],"offsets":[[105,130]],"normalized":[{"db_name":"MESH","db_id":"D006463"}]},{"id":"9329","type":"Disease","text":["HUS"],"offsets":[[132,135]],"normalized":[{"db_name":"MESH","db_id":"D006463"}]},{"id":"9330","type":"Chemical","text":["oral contraceptives"],"offsets":[[155,174]],"normalized":[{"db_name":"MESH","db_id":"D003276"}]},{"id":"9331","type":"Chemical","text":["heparin"],"offsets":[[197,204]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"9332","type":"Chemical","text":["dipyridamole"],"offsets":[[206,218]],"normalized":[{"db_name":"MESH","db_id":"D004176"}]},{"id":"9333","type":"Disease","text":["anuria"],"offsets":[[343,349]],"normalized":[{"db_name":"MESH","db_id":"D001002"}]},{"id":"9334","type":"Disease","text":["HUS"],"offsets":[[425,428]],"normalized":[{"db_name":"MESH","db_id":"D006463"}]},{"id":"9335","type":"Disease","text":["oliguria"],"offsets":[[498,506]],"normalized":[{"db_name":"MESH","db_id":"D009846"}]},{"id":"9336","type":"Disease","text":["HUS"],"offsets":[[593,596]],"normalized":[{"db_name":"MESH","db_id":"D006463"}]},{"id":"9337","type":"Disease","text":["hypertension"],"offsets":[[704,716]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"9338","type":"Disease","text":["microangiopathic hemolytic anemia"],"offsets":[[721,754]],"normalized":[{"db_name":"MESH","db_id":"D000743"}]}],"events":[],"coreferences":[],"relations":[{"id":"9339","type":"CID","arg1_id":"9330","arg2_id":"9327","normalized":[]},{"id":"9340","type":"CID","arg1_id":"9330","arg2_id":"9328","normalized":[]},{"id":"9341","type":"CID","arg1_id":"9330","arg2_id":"9329","normalized":[]},{"id":"9342","type":"CID","arg1_id":"9330","arg2_id":"9334","normalized":[]},{"id":"9343","type":"CID","arg1_id":"9330","arg2_id":"9336","normalized":[]}]}
{"id":"9344","document_id":"983936","passages":[{"id":"9345","type":"title","text":["Effects of acetylsalicylic acid, dipyridamole, and hydrocortisone on epinephrine-induced myocardial injury in dogs."],"offsets":[[0,115]]},{"id":"9346","type":"abstract","text":["A reproducible model for producing diffuse myocardial injury (epinephrine infusion) has been developed to study the cardioprotective effects of agents or maneuvers which might alter the evolution of acute myocardial infarction. Infusions of epinephrine (4 mug per kilogram per minute for 6 hours) increased radiocalcium uptakes into intact myocardium and each of its subcellular components with the mitochondrial fraction showing the most consistent changes when compared to saline-infused control animals (4,957 vs. 827 counts per minute per gram of dried tissue or fraction). Myocardial concentrations of calcium also increased significantly (12.0 vs. 5.0 mg.per 100 Gm. of fat-free dry weight). Infusions of calcium chloride sufficient to raise serum calcium concentrations 2 mEq. per liter failed to increase calcium influx into the myocardial cell. Mitochondrial radiocalcium uptakes were significantly decreased in animals pretreated with acetylsalicylic acid or dipyridamole or when hydrocortisone was added to the epinephrine infusion (2,682,2,803, and 3,424 counts per minute per gram of dried fraction, respectively). Myocardial calcium concentrations also were decreased (11.2, 8.3, and 8.9 mg. per 100 Gm. of fat-free dry weight, respectively) in the three treatment groups, being significantly decreased only in the last two. Evidence of microscopic damage was graded as less severe in the three treatment groups. Acetylsalicylic acid, dipyridamole, and hydrocortisone all appear to have cardioprotective effects when tested in this model."],"offsets":[[116,1668]]}],"entities":[{"id":"9347","type":"Chemical","text":["acetylsalicylic acid"],"offsets":[[11,31]],"normalized":[{"db_name":"MESH","db_id":"D001241"}]},{"id":"9348","type":"Chemical","text":["dipyridamole"],"offsets":[[33,45]],"normalized":[{"db_name":"MESH","db_id":"D004176"}]},{"id":"9349","type":"Chemical","text":["hydrocortisone"],"offsets":[[51,65]],"normalized":[{"db_name":"MESH","db_id":"D006854"}]},{"id":"9350","type":"Chemical","text":["epinephrine"],"offsets":[[69,80]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"9351","type":"Disease","text":["myocardial injury"],"offsets":[[89,106]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"9352","type":"Disease","text":["myocardial injury"],"offsets":[[159,176]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"9353","type":"Chemical","text":["epinephrine"],"offsets":[[178,189]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"9354","type":"Disease","text":["myocardial infarction"],"offsets":[[321,342]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"9355","type":"Chemical","text":["epinephrine"],"offsets":[[357,368]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"9356","type":"Chemical","text":["radiocalcium"],"offsets":[[423,435]],"normalized":[{"db_name":"MESH","db_id":"D002132"}]},{"id":"9357","type":"Chemical","text":["calcium"],"offsets":[[723,730]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"9358","type":"Chemical","text":["calcium chloride"],"offsets":[[827,843]],"normalized":[{"db_name":"MESH","db_id":"D002122"}]},{"id":"9359","type":"Chemical","text":["calcium"],"offsets":[[870,877]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"9360","type":"Chemical","text":["calcium"],"offsets":[[929,936]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"9361","type":"Chemical","text":["radiocalcium"],"offsets":[[984,996]],"normalized":[{"db_name":"MESH","db_id":"D002132"}]},{"id":"9362","type":"Chemical","text":["acetylsalicylic acid"],"offsets":[[1061,1081]],"normalized":[{"db_name":"MESH","db_id":"D001241"}]},{"id":"9363","type":"Chemical","text":["dipyridamole"],"offsets":[[1085,1097]],"normalized":[{"db_name":"MESH","db_id":"D004176"}]},{"id":"9364","type":"Chemical","text":["hydrocortisone"],"offsets":[[1106,1120]],"normalized":[{"db_name":"MESH","db_id":"D006854"}]},{"id":"9365","type":"Chemical","text":["epinephrine"],"offsets":[[1138,1149]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"9366","type":"Chemical","text":["calcium"],"offsets":[[1255,1262]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"9367","type":"Chemical","text":["Acetylsalicylic acid"],"offsets":[[1543,1563]],"normalized":[{"db_name":"MESH","db_id":"D001241"}]},{"id":"9368","type":"Chemical","text":["dipyridamole"],"offsets":[[1565,1577]],"normalized":[{"db_name":"MESH","db_id":"D004176"}]},{"id":"9369","type":"Chemical","text":["hydrocortisone"],"offsets":[[1583,1597]],"normalized":[{"db_name":"MESH","db_id":"D006854"}]}],"events":[],"coreferences":[],"relations":[{"id":"9370","type":"CID","arg1_id":"9350","arg2_id":"9351","normalized":[]},{"id":"9371","type":"CID","arg1_id":"9350","arg2_id":"9352","normalized":[]},{"id":"9372","type":"CID","arg1_id":"9353","arg2_id":"9351","normalized":[]},{"id":"9373","type":"CID","arg1_id":"9353","arg2_id":"9352","normalized":[]},{"id":"9374","type":"CID","arg1_id":"9355","arg2_id":"9351","normalized":[]},{"id":"9375","type":"CID","arg1_id":"9355","arg2_id":"9352","normalized":[]},{"id":"9376","type":"CID","arg1_id":"9365","arg2_id":"9351","normalized":[]},{"id":"9377","type":"CID","arg1_id":"9365","arg2_id":"9352","normalized":[]}]}
{"id":"9378","document_id":"1428568","passages":[{"id":"9379","type":"title","text":["Changes in depressive status associated with topical beta-blockers."],"offsets":[[0,67]]},{"id":"9380","type":"abstract","text":["Depression and sexual dysfunction have been related to side effects of topical beta-blockers. We performed a preliminary study in order to determine any difference between a non selective beta-blocker (timolol) and a selective beta-blocker (betaxolol) regarding CNS side effects. Eight glaucomatous patients chronically treated with timolol 0.5%\/12h, suffering from depression diagnosed through DMS-III-R criteria, were included in the study. During the six-month follow up, depression was quantified through the Beck and Zung-Conde scales every two months. In a double blind cross-over study with control group, the patients under timolol treatment presented higher depression values measured through the Beck and the Zung-Conde scales (p < 0.001 vs control). These results suggest that betaxolol could be less of a depression-inducer than timolol in predisposed patients."],"offsets":[[68,941]]}],"entities":[{"id":"9381","type":"Disease","text":["depressive"],"offsets":[[11,21]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"9382","type":"Disease","text":["Depression"],"offsets":[[68,78]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"9383","type":"Disease","text":["sexual dysfunction"],"offsets":[[83,101]],"normalized":[{"db_name":"MESH","db_id":"D012735"}]},{"id":"9384","type":"Chemical","text":["timolol"],"offsets":[[270,277]],"normalized":[{"db_name":"MESH","db_id":"D013999"}]},{"id":"9385","type":"Chemical","text":["betaxolol"],"offsets":[[309,318]],"normalized":[{"db_name":"MESH","db_id":"D015784"}]},{"id":"9386","type":"Disease","text":["glaucomatous"],"offsets":[[354,366]],"normalized":[{"db_name":"MESH","db_id":"D005901"}]},{"id":"9387","type":"Chemical","text":["timolol"],"offsets":[[401,408]],"normalized":[{"db_name":"MESH","db_id":"D013999"}]},{"id":"9388","type":"Disease","text":["depression"],"offsets":[[434,444]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"9389","type":"Disease","text":["depression"],"offsets":[[543,553]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"9390","type":"Chemical","text":["timolol"],"offsets":[[700,707]],"normalized":[{"db_name":"MESH","db_id":"D013999"}]},{"id":"9391","type":"Disease","text":["depression"],"offsets":[[735,745]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"9392","type":"Chemical","text":["betaxolol"],"offsets":[[856,865]],"normalized":[{"db_name":"MESH","db_id":"D015784"}]},{"id":"9393","type":"Disease","text":["depression"],"offsets":[[885,895]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"9394","type":"Chemical","text":["timolol"],"offsets":[[909,916]],"normalized":[{"db_name":"MESH","db_id":"D013999"}]}],"events":[],"coreferences":[],"relations":[{"id":"9395","type":"CID","arg1_id":"9384","arg2_id":"9381","normalized":[]},{"id":"9396","type":"CID","arg1_id":"9384","arg2_id":"9382","normalized":[]},{"id":"9397","type":"CID","arg1_id":"9384","arg2_id":"9388","normalized":[]},{"id":"9398","type":"CID","arg1_id":"9384","arg2_id":"9389","normalized":[]},{"id":"9399","type":"CID","arg1_id":"9384","arg2_id":"9391","normalized":[]},{"id":"9400","type":"CID","arg1_id":"9384","arg2_id":"9393","normalized":[]},{"id":"9401","type":"CID","arg1_id":"9387","arg2_id":"9381","normalized":[]},{"id":"9402","type":"CID","arg1_id":"9387","arg2_id":"9382","normalized":[]},{"id":"9403","type":"CID","arg1_id":"9387","arg2_id":"9388","normalized":[]},{"id":"9404","type":"CID","arg1_id":"9387","arg2_id":"9389","normalized":[]},{"id":"9405","type":"CID","arg1_id":"9387","arg2_id":"9391","normalized":[]},{"id":"9406","type":"CID","arg1_id":"9387","arg2_id":"9393","normalized":[]},{"id":"9407","type":"CID","arg1_id":"9390","arg2_id":"9381","normalized":[]},{"id":"9408","type":"CID","arg1_id":"9390","arg2_id":"9382","normalized":[]},{"id":"9409","type":"CID","arg1_id":"9390","arg2_id":"9388","normalized":[]},{"id":"9410","type":"CID","arg1_id":"9390","arg2_id":"9389","normalized":[]},{"id":"9411","type":"CID","arg1_id":"9390","arg2_id":"9391","normalized":[]},{"id":"9412","type":"CID","arg1_id":"9390","arg2_id":"9393","normalized":[]},{"id":"9413","type":"CID","arg1_id":"9394","arg2_id":"9381","normalized":[]},{"id":"9414","type":"CID","arg1_id":"9394","arg2_id":"9382","normalized":[]},{"id":"9415","type":"CID","arg1_id":"9394","arg2_id":"9388","normalized":[]},{"id":"9416","type":"CID","arg1_id":"9394","arg2_id":"9389","normalized":[]},{"id":"9417","type":"CID","arg1_id":"9394","arg2_id":"9391","normalized":[]},{"id":"9418","type":"CID","arg1_id":"9394","arg2_id":"9393","normalized":[]}]}
{"id":"9419","document_id":"1720453","passages":[{"id":"9420","type":"title","text":["Long-term follow-up of ifosfamide renal toxicity in children treated for malignant mesenchymal tumors: an International Society of Pediatric Oncology report."],"offsets":[[0,157]]},{"id":"9421","type":"abstract","text":["The renal function of 74 children with malignant mesenchymal tumors in complete remission and who have received the same ifosfamide chemotherapy protocol (International Society of Pediatric Oncology Malignant Mesenchymal Tumor Study 84 [SIOP MMT 84]) were studied 1 year after the completion of treatment. Total cumulative doses were 36 or 60 g\/m2 of ifosfamide (six or 10 cycles of ifosfamide, vincristine, and dactinomycin [IVA]). None of them had received cisplatin chemotherapy. Ages ranged from 4 months to 17 years; 58 patients were males and 42 females. The most common primary tumor site was the head and neck. Renal function was investigated by measuring plasma and urinary electrolytes, glucosuria, proteinuria, aminoaciduria, urinary pH, osmolarity, creatinine clearance, phosphate tubular reabsorption, beta 2 microglobulinuria, and lysozymuria. Fifty-eight patients (78%) had normal renal tests, whereas 16 patients (22%) had renal abnormalities. Two subsets of patients were identified from this latter group: the first included four patients (5% of the total population) who developed major toxicity resulting in Fanconi's syndrome (TDFS); and the second group included five patients with elevated beta 2 microglobulinuria and low phosphate reabsorption. The remaining seven patients had isolated beta 2 microglobulinuria. Severe toxicity was correlated with the higher cumulative dose of 60 g\/m2 of ifosfamide, a younger age (less than 2 1\/2 years old), and a predominance of vesicoprostatic tumor involvement. This low percentage (5%) of TDFS must be evaluated with respect to the efficacy of ifosfamide in the treatment of mesenchymal tumors in children."],"offsets":[[158,1830]]}],"entities":[{"id":"9422","type":"Chemical","text":["ifosfamide"],"offsets":[[23,33]],"normalized":[{"db_name":"MESH","db_id":"D007069"}]},{"id":"9423","type":"Disease","text":["renal toxicity"],"offsets":[[34,48]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"9424","type":"Disease","text":["malignant mesenchymal tumors"],"offsets":[[73,101]],"normalized":[{"db_name":"MESH","db_id":"C535700"}]},{"id":"9425","type":"Disease","text":["malignant mesenchymal tumors"],"offsets":[[197,225]],"normalized":[{"db_name":"MESH","db_id":"C535700"}]},{"id":"9426","type":"Chemical","text":["ifosfamide"],"offsets":[[279,289]],"normalized":[{"db_name":"MESH","db_id":"D007069"}]},{"id":"9427","type":"Disease","text":["Malignant Mesenchymal Tumor"],"offsets":[[357,384]],"normalized":[{"db_name":"MESH","db_id":"C535700"}]},{"id":"9428","type":"Chemical","text":["ifosfamide"],"offsets":[[509,519]],"normalized":[{"db_name":"MESH","db_id":"D007069"}]},{"id":"9429","type":"Chemical","text":["ifosfamide, vincristine, and dactinomycin"],"offsets":[[541,582]],"normalized":[{"db_name":"MESH","db_id":"C064227"}]},{"id":"9430","type":"Chemical","text":["IVA"],"offsets":[[584,587]],"normalized":[{"db_name":"MESH","db_id":"C064227"}]},{"id":"9431","type":"Chemical","text":["cisplatin"],"offsets":[[617,626]],"normalized":[{"db_name":"MESH","db_id":"D002945"}]},{"id":"9432","type":"Disease","text":["tumor"],"offsets":[[743,748]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"9433","type":"Disease","text":["glucosuria"],"offsets":[[855,865]],"normalized":[{"db_name":"MESH","db_id":"D006030"}]},{"id":"9434","type":"Disease","text":["proteinuria"],"offsets":[[867,878]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]},{"id":"9435","type":"Disease","text":["aminoaciduria"],"offsets":[[880,893]],"normalized":[{"db_name":"MESH","db_id":"D000608"}]},{"id":"9436","type":"Chemical","text":["creatinine"],"offsets":[[919,929]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"9437","type":"Chemical","text":["phosphate"],"offsets":[[941,950]],"normalized":[{"db_name":"MESH","db_id":"D010710"}]},{"id":"9438","type":"Disease","text":["renal abnormalities"],"offsets":[[1097,1116]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"9439","type":"Disease","text":["toxicity"],"offsets":[[1264,1272]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"9440","type":"Disease","text":["Fanconi's syndrome"],"offsets":[[1286,1304]],"normalized":[{"db_name":"MESH","db_id":"D005198"}]},{"id":"9441","type":"Disease","text":["TDFS"],"offsets":[[1306,1310]],"normalized":[{"db_name":"MESH","db_id":"D005198"}]},{"id":"9442","type":"Chemical","text":["phosphate"],"offsets":[[1404,1413]],"normalized":[{"db_name":"MESH","db_id":"D010710"}]},{"id":"9443","type":"Disease","text":["toxicity"],"offsets":[[1503,1511]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"9444","type":"Chemical","text":["ifosfamide"],"offsets":[[1573,1583]],"normalized":[{"db_name":"MESH","db_id":"D007069"}]},{"id":"9445","type":"Disease","text":["tumor"],"offsets":[[1666,1671]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"9446","type":"Chemical","text":["ifosfamide"],"offsets":[[1768,1778]],"normalized":[{"db_name":"MESH","db_id":"D007069"}]},{"id":"9447","type":"Disease","text":["mesenchymal tumors"],"offsets":[[1799,1817]],"normalized":[{"db_name":"MESH","db_id":"C535700"}]}],"events":[],"coreferences":[],"relations":[{"id":"9448","type":"CID","arg1_id":"9422","arg2_id":"9440","normalized":[]},{"id":"9449","type":"CID","arg1_id":"9422","arg2_id":"9441","normalized":[]},{"id":"9450","type":"CID","arg1_id":"9426","arg2_id":"9440","normalized":[]},{"id":"9451","type":"CID","arg1_id":"9426","arg2_id":"9441","normalized":[]},{"id":"9452","type":"CID","arg1_id":"9428","arg2_id":"9440","normalized":[]},{"id":"9453","type":"CID","arg1_id":"9428","arg2_id":"9441","normalized":[]},{"id":"9454","type":"CID","arg1_id":"9444","arg2_id":"9440","normalized":[]},{"id":"9455","type":"CID","arg1_id":"9444","arg2_id":"9441","normalized":[]},{"id":"9456","type":"CID","arg1_id":"9446","arg2_id":"9440","normalized":[]},{"id":"9457","type":"CID","arg1_id":"9446","arg2_id":"9441","normalized":[]},{"id":"9458","type":"CID","arg1_id":"9422","arg2_id":"9423","normalized":[]},{"id":"9459","type":"CID","arg1_id":"9422","arg2_id":"9438","normalized":[]},{"id":"9460","type":"CID","arg1_id":"9426","arg2_id":"9423","normalized":[]},{"id":"9461","type":"CID","arg1_id":"9426","arg2_id":"9438","normalized":[]},{"id":"9462","type":"CID","arg1_id":"9428","arg2_id":"9423","normalized":[]},{"id":"9463","type":"CID","arg1_id":"9428","arg2_id":"9438","normalized":[]},{"id":"9464","type":"CID","arg1_id":"9444","arg2_id":"9423","normalized":[]},{"id":"9465","type":"CID","arg1_id":"9444","arg2_id":"9438","normalized":[]},{"id":"9466","type":"CID","arg1_id":"9446","arg2_id":"9423","normalized":[]},{"id":"9467","type":"CID","arg1_id":"9446","arg2_id":"9438","normalized":[]}]}
{"id":"9468","document_id":"1833784","passages":[{"id":"9469","type":"title","text":["Evidence for an involvement of D1 and D2 dopamine receptors in mediating nicotine-induced hyperactivity in rats."],"offsets":[[0,112]]},{"id":"9470","type":"abstract","text":["Previous studies have suggested that repeated exposure of rats to the drug or to the experimental environment is necessary to observe nicotine-induced locomotor stimulation. In the present study the role of habituation to the experimental environment on the stimulant effect of nicotine in rats was examined. In addition, the role of dopamine receptors in mediating nicotine-induced locomotor stimulation was investigated by examining the effects of selective D1 and D2 dopamine receptor antagonists on activity induced by nicotine. Locomotor activity was assessed in male Sprague-Dawley rats tested in photocell cages. Nicotine (1.0 mg\/kg) caused a significant increase in locomotor activity in rats that were habituated to the test environment, but had only a weak and delayed stimulant action in rats that were unfamiliar with the test environment. The stimulant action of nicotine was blocked by the central nicotinic antagonist mecamylamine but not by the peripheral nicotinic blocker hexamethonium, indicating that the response is probably mediated by central nicotinic receptors. Nicotine-induced hyperactivity was blocked by the selective D1 antagonist SCH 23390, the selective D2 antagonist raclopride and the D1\/D2 antagonist fluphenazine. Pretreatment with the D2 agonist PHNO enhanced nicotine-induced hyperactivity, whereas the D1 agonist SKF 38393 had no effect. The results indicate that acute nicotine injection induces a pronounced hyperactivity in rats habituated to the test environment. The effect appears to be mediated by central nicotine receptors, possibly located on dopaminergic neurons, and also requires the activation of both D1 and D2 dopamine receptors."],"offsets":[[113,1797]]}],"entities":[{"id":"9471","type":"Chemical","text":["dopamine"],"offsets":[[41,49]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"9472","type":"Chemical","text":["nicotine"],"offsets":[[73,81]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"9473","type":"Disease","text":["hyperactivity"],"offsets":[[90,103]],"normalized":[{"db_name":"MESH","db_id":"D006948"}]},{"id":"9474","type":"Chemical","text":["nicotine"],"offsets":[[247,255]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"9475","type":"Chemical","text":["nicotine"],"offsets":[[391,399]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"9476","type":"Chemical","text":["dopamine"],"offsets":[[447,455]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"9477","type":"Chemical","text":["nicotine"],"offsets":[[479,487]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"9478","type":"Chemical","text":["dopamine"],"offsets":[[583,591]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"9479","type":"Chemical","text":["nicotine"],"offsets":[[636,644]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"9480","type":"Chemical","text":["Nicotine"],"offsets":[[733,741]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"9481","type":"Disease","text":["increase in locomotor activity"],"offsets":[[775,805]],"normalized":[{"db_name":"MESH","db_id":"D006948"}]},{"id":"9482","type":"Chemical","text":["nicotine"],"offsets":[[989,997]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"9483","type":"Chemical","text":["mecamylamine"],"offsets":[[1046,1058]],"normalized":[{"db_name":"MESH","db_id":"D008464"}]},{"id":"9484","type":"Chemical","text":["hexamethonium"],"offsets":[[1103,1116]],"normalized":[{"db_name":"MESH","db_id":"D018738"}]},{"id":"9485","type":"Chemical","text":["Nicotine"],"offsets":[[1200,1208]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"9486","type":"Disease","text":["hyperactivity"],"offsets":[[1217,1230]],"normalized":[{"db_name":"MESH","db_id":"D006948"}]},{"id":"9487","type":"Chemical","text":["SCH 23390"],"offsets":[[1274,1283]],"normalized":[{"db_name":"MESH","db_id":"C534628"}]},{"id":"9488","type":"Chemical","text":["raclopride"],"offsets":[[1313,1323]],"normalized":[{"db_name":"MESH","db_id":"D020891"}]},{"id":"9489","type":"Chemical","text":["fluphenazine"],"offsets":[[1349,1361]],"normalized":[{"db_name":"MESH","db_id":"D005476"}]},{"id":"9490","type":"Chemical","text":["PHNO"],"offsets":[[1396,1400]],"normalized":[]},{"id":"9491","type":"Chemical","text":["nicotine"],"offsets":[[1410,1418]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"9492","type":"Disease","text":["hyperactivity"],"offsets":[[1427,1440]],"normalized":[{"db_name":"MESH","db_id":"D006948"}]},{"id":"9493","type":"Chemical","text":["SKF 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{"id":"9553","document_id":"1867351","passages":[{"id":"9554","type":"title","text":["Neuropsychiatric side effects after the use of mefloquine."],"offsets":[[0,58]]},{"id":"9555","type":"abstract","text":["This study describes neuropsychiatric side effects in patients after treatment with mefloquine. Reactions consisted mainly of seizures, acute psychoses, anxiety neurosis, and major disturbances of sleep-wake rhythm. Side effects occurred after both therapeutic and prophylactic intake and were graded from moderate to severe. In a risk analysis of neuropsychiatric side effects in Germany, it is estimated that one of 8,000 mefloquine users suffers from such reactions. The incidence calculation revealed that one of 215 therapeutic users had reactions, compared with one of 13,000 in the prophylaxis group, making the risk of neuropsychiatric reactions after mefloquine treatment 60 times higher than after prophylaxis. Therefore, certain limitations for malaria prophylaxis and treatment with mefloquine are recommended."],"offsets":[[59,881]]}],"entities":[{"id":"9556","type":"Chemical","text":["mefloquine"],"offsets":[[47,57]],"normalized":[{"db_name":"MESH","db_id":"D015767"}]},{"id":"9557","type":"Chemical","text":["mefloquine"],"offsets":[[143,153]],"normalized":[{"db_name":"MESH","db_id":"D015767"}]},{"id":"9558","type":"Disease","text":["seizures"],"offsets":[[185,193]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"9559","type":"Disease","text":["psychoses"],"offsets":[[201,210]],"normalized":[{"db_name":"MESH","db_id":"D011605"}]},{"id":"9560","type":"Disease","text":["anxiety neurosis"],"offsets":[[212,228]],"normalized":[{"db_name":"MESH","db_id":"D001008"}]},{"id":"9561","type":"Disease","text":["disturbances of sleep-wake rhythm"],"offsets":[[240,273]],"normalized":[{"db_name":"MESH","db_id":"D012893"}]},{"id":"9562","type":"Chemical","text":["mefloquine"],"offsets":[[483,493]],"normalized":[{"db_name":"MESH","db_id":"D015767"}]},{"id":"9563","type":"Chemical","text":["mefloquine"],"offsets":[[719,729]],"normalized":[{"db_name":"MESH","db_id":"D015767"}]},{"id":"9564","type":"Disease","text":["malaria"],"offsets":[[815,822]],"normalized":[{"db_name":"MESH","db_id":"D008288"}]},{"id":"9565","type":"Chemical","text":["mefloquine"],"offsets":[[854,864]],"normalized":[{"db_name":"MESH","db_id":"D015767"}]}],"events":[],"coreferences":[],"relations":[{"id":"9566","type":"CID","arg1_id":"9556","arg2_id":"9561","normalized":[]},{"id":"9567","type":"CID","arg1_id":"9557","arg2_id":"9561","normalized":[]},{"id":"9568","type":"CID","arg1_id":"9562","arg2_id":"9561","normalized":[]},{"id":"9569","type":"CID","arg1_id":"9563","arg2_id":"9561","normalized":[]},{"id":"9570","type":"CID","arg1_id":"9565","arg2_id":"9561","normalized":[]},{"id":"9571","type":"CID","arg1_id":"9556","arg2_id":"9559","normalized":[]},{"id":"9572","type":"CID","arg1_id":"9557","arg2_id":"9559","normalized":[]},{"id":"9573","type":"CID","arg1_id":"9562","arg2_id":"9559","normalized":[]},{"id":"9574","type":"CID","arg1_id":"9563","arg2_id":"9559","normalized":[]},{"id":"9575","type":"CID","arg1_id":"9565","arg2_id":"9559","normalized":[]},{"id":"9576","type":"CID","arg1_id":"9556","arg2_id":"9560","normalized":[]},{"id":"9577","type":"CID","arg1_id":"9557","arg2_id":"9560","normalized":[]},{"id":"9578","type":"CID","arg1_id":"9562","arg2_id":"9560","normalized":[]},{"id":"9579","type":"CID","arg1_id":"9563","arg2_id":"9560","normalized":[]},{"id":"9580","type":"CID","arg1_id":"9565","arg2_id":"9560","normalized":[]},{"id":"9581","type":"CID","arg1_id":"9556","arg2_id":"9558","normalized":[]},{"id":"9582","type":"CID","arg1_id":"9557","arg2_id":"9558","normalized":[]},{"id":"9583","type":"CID","arg1_id":"9562","arg2_id":"9558","normalized":[]},{"id":"9584","type":"CID","arg1_id":"9563","arg2_id":"9558","normalized":[]},{"id":"9585","type":"CID","arg1_id":"9565","arg2_id":"9558","normalized":[]}]}
{"id":"9586","document_id":"2070391","passages":[{"id":"9587","type":"title","text":["Reduction in injection pain using buffered lidocaine as a local anesthetic before cardiac catheterization."],"offsets":[[0,106]]},{"id":"9588","type":"abstract","text":["Previous reports have suggested that pain associated with the injection of lidocaine is related to the acidic pH of the solution. To determine if the addition of a buffering solution to adjust the pH of lidocaine into the physiologic range would reduce pain during injection, we performed a blinded randomized study in patients undergoing cardiac catheterization. Twenty patients were asked to quantify the severity of pain after receiving standard lidocaine in one femoral area and buffered lidocaine in the opposite femoral area. The mean pain score for buffered lidocaine was significantly lower than the mean score for standard lidocaine (2.7 +\/- 1.9 vs. 3.8 +\/- 2.2, P = 0.03). The pH adjustment of standard lidocaine can be accomplished easily in the catheterization laboratory before injection and results in a reduction of the pain occurring during the infiltration of tissues."],"offsets":[[107,992]]}],"entities":[{"id":"9589","type":"Disease","text":["pain"],"offsets":[[23,27]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"9590","type":"Chemical","text":["lidocaine"],"offsets":[[43,52]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"9591","type":"Disease","text":["pain"],"offsets":[[144,148]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"9592","type":"Chemical","text":["lidocaine"],"offsets":[[182,191]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"9593","type":"Chemical","text":["lidocaine"],"offsets":[[310,319]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"9594","type":"Disease","text":["pain"],"offsets":[[360,364]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"9595","type":"Disease","text":["pain"],"offsets":[[526,530]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"9596","type":"Chemical","text":["lidocaine"],"offsets":[[556,565]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"9597","type":"Chemical","text":["lidocaine"],"offsets":[[599,608]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"9598","type":"Disease","text":["pain"],"offsets":[[648,652]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"9599","type":"Chemical","text":["lidocaine"],"offsets":[[672,681]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"9600","type":"Chemical","text":["lidocaine"],"offsets":[[739,748]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"9601","type":"Chemical","text":["lidocaine"],"offsets":[[820,829]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"9602","type":"Disease","text":["pain"],"offsets":[[942,946]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]}],"events":[],"coreferences":[],"relations":[{"id":"9603","type":"CID","arg1_id":"9590","arg2_id":"9589","normalized":[]},{"id":"9604","type":"CID","arg1_id":"9590","arg2_id":"9591","normalized":[]},{"id":"9605","type":"CID","arg1_id":"9590","arg2_id":"9594","normalized":[]},{"id":"9606","type":"CID","arg1_id":"9590","arg2_id":"9595","normalized":[]},{"id":"9607","type":"CID","arg1_id":"9590","arg2_id":"9598","normalized":[]},{"id":"9608","type":"CID","arg1_id":"9590","arg2_id":"9602","normalized":[]},{"id":"9609","type":"CID","arg1_id":"9592","arg2_id":"9589","normalized":[]},{"id":"9610","type":"CID","arg1_id":"9592","arg2_id":"9591","normalized":[]},{"id":"9611","type":"CID","arg1_id":"9592","arg2_id":"9594","normalized":[]},{"id":"9612","type":"CID","arg1_id":"9592","arg2_id":"9595","normalized":[]},{"id":"9613","type":"CID","arg1_id":"9592","arg2_id":"9598","normalized":[]},{"id":"9614","type":"CID","arg1_id":"9592","arg2_id":"9602","normalized":[]},{"id":"9615","type":"CID","arg1_id":"9593","arg2_id":"9589","normalized":[]},{"id":"9616","type":"CID","arg1_id":"9593","arg2_id":"9591","normalized":[]},{"id":"9617","type":"CID","arg1_id":"9593","arg2_id":"9594","normalized":[]},{"id":"9618","type":"CID","arg1_id":"9593","arg2_id":"9595","normalized":[]},{"id":"9619","type":"CID","arg1_id":"9593","arg2_id":"9598","normalized":[]},{"id":"9620","type":"CID","arg1_id":"9593","arg2_id":"9602","normalized":[]},{"id":"9621","type":"CID","arg1_id":"9596","arg2_id":"9589","normalized":[]},{"id":"9622","type":"CID","arg1_id":"9596","arg2_id":"9591","normalized":[]},{"id":"9623","type":"CID","arg1_id":"9596","arg2_id":"9594","normalized":[]},{"id":"9624","type":"CID","arg1_id":"9596","arg2_id":"9595","normalized":[]},{"id":"9625","type":"CID","arg1_id":"9596","arg2_id":"9598","normalized":[]},{"id":"9626","type":"CID","arg1_id":"9596","arg2_id":"9602","normalized":[]},{"id":"9627","type":"CID","arg1_id":"9597","arg2_id":"9589","normalized":[]},{"id":"9628","type":"CID","arg1_id":"9597","arg2_id":"9591","normalized":[]},{"id":"9629","type":"CID","arg1_id":"9597","arg2_id":"9594","normalized":[]},{"id":"9630","type":"CID","arg1_id":"9597","arg2_id":"9595","normalized":[]},{"id":"9631","type":"CID","arg1_id":"9597","arg2_id":"9598","normalized":[]},{"id":"9632","type":"CID","arg1_id":"9597","arg2_id":"9602","normalized":[]},{"id":"9633","type":"CID","arg1_id":"9599","arg2_id":"9589","normalized":[]},{"id":"9634","type":"CID","arg1_id":"9599","arg2_id":"9591","normalized":[]},{"id":"9635","type":"CID","arg1_id":"9599","arg2_id":"9594","normalized":[]},{"id":"9636","type":"CID","arg1_id":"9599","arg2_id":"9595","normalized":[]},{"id":"9637","type":"CID","arg1_id":"9599","arg2_id":"9598","normalized":[]},{"id":"9638","type":"CID","arg1_id":"9599","arg2_id":"9602","normalized":[]},{"id":"9639","type":"CID","arg1_id":"9600","arg2_id":"9589","normalized":[]},{"id":"9640","type":"CID","arg1_id":"9600","arg2_id":"9591","normalized":[]},{"id":"9641","type":"CID","arg1_id":"9600","arg2_id":"9594","normalized":[]},{"id":"9642","type":"CID","arg1_id":"9600","arg2_id":"9595","normalized":[]},{"id":"9643","type":"CID","arg1_id":"9600","arg2_id":"9598","normalized":[]},{"id":"9644","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{"id":"9651","document_id":"2266990","passages":[{"id":"9652","type":"title","text":["Randomized, double-blind trial of mazindol in Duchenne dystrophy."],"offsets":[[0,65]]},{"id":"9653","type":"abstract","text":["There is evidence that growth hormone may be related to the progression of weakness in Duchenne dystrophy. We conducted a 12-month controlled trial of mazindol, a putative growth hormone secretion inhibitor, in 83 boys with Duchenne dystrophy. Muscle strength, contractures, functional ability and pulmonary function were tested at baseline, and 6 and 12 months after treatment with mazindol (3 mg\/d) or placebo. The study was designed to have a power of greater than 0.90 to detect a slowing to 25% of the expected rate of progression of weakness at P less than 0.05. Mazindol did not benefit strength at any point in the study. Side effects attributable to mazindol included decreased appetite (36%), dry mouth (10%), behavioral change (22%), and gastrointestinal symptoms (18%); mazindol dosage was reduced in 43% of patients. The effect of mazindol on GH secretion was estimated indirectly by comparing the postabsorptive IGF-I levels obtained following 3, 6, 9, and 12 months in the mazindol treated to those in the placebo groups. Although mazindol-treated patients gained less weight and height than placebo-treated patients, no significant effect on IGF-I levels was observed. Mazindol doses not slow the progression of weakness in Duchenne dystrophy."],"offsets":[[66,1325]]}],"entities":[{"id":"9654","type":"Chemical","text":["mazindol"],"offsets":[[34,42]],"normalized":[{"db_name":"MESH","db_id":"D008454"}]},{"id":"9655","type":"Disease","text":["Duchenne dystrophy"],"offsets":[[46,64]],"normalized":[{"db_name":"MESH","db_id":"D020388"}]},{"id":"9656","type":"Disease","text":["weakness"],"offsets":[[141,149]],"normalized":[{"db_name":"MESH","db_id":"D018908"}]},{"id":"9657","type":"Disease","text":["Duchenne dystrophy"],"offsets":[[153,171]],"normalized":[{"db_name":"MESH","db_id":"D020388"}]},{"id":"9658","type":"Chemical","text":["mazindol"],"offsets":[[217,225]],"normalized":[{"db_name":"MESH","db_id":"D008454"}]},{"id":"9659","type":"Disease","text":["Duchenne 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{"id":"9704","document_id":"2348231","passages":[{"id":"9705","type":"title","text":["Pentoxifylline (Trental) does not inhibit dipyridamole-induced coronary hyperemia: implications for dipyridamole-thallium-201 myocardial imaging."],"offsets":[[0,145]]},{"id":"9706","type":"abstract","text":["Dipyridamole-thallium-201 imaging is often performed in patients unable to exercise because of peripheral vascular disease. Many of these patients are taking pentoxifylline (Trental), a methylxanthine derivative which may improve intermittent claudication. Whether pentoxifylline inhibits dipyridamole-induced coronary hyperemia like other methylxanthines such as theophylline and should be stopped prior to dipyridamole-thallium-201 imaging is unknown. Therefore, we studied the hyperemic response to dipyridamole in seven open-chest anesthetized dogs after pretreatment with either pentoxifylline (0, 7.5, or 15 mg\/kg i.v.) or theophylline (3 mg\/kg i.v.). Baseline circumflex coronary blood flows did not differ significantly among treatment groups. Dipyridamole significantly increased coronary blood flow before and after 7.5 or 15 mm\/kg i.v. pentoxifylline (p less than 0.002). Neither dose of pentoxifylline significantly decreased the dipyridamole-induced hyperemia, while peak coronary blood flow was significantly lower after theophylline (p less than 0.01). We conclude that pentoxyifylline does not inhibit dipyridamole-induced coronary hyperemia even at high doses."],"offsets":[[146,1323]]}],"entities":[{"id":"9707","type":"Chemical","text":["Pentoxifylline"],"offsets":[[0,14]],"normalized":[{"db_name":"MESH","db_id":"D010431"}]},{"id":"9708","type":"Chemical","text":["Trental"],"offsets":[[16,23]],"normalized":[{"db_name":"MESH","db_id":"D010431"}]},{"id":"9709","type":"Chemical","text":["dipyridamole"],"offsets":[[42,54]],"normalized":[{"db_name":"MESH","db_id":"D004176"}]},{"id":"9710","type":"Disease","text":["hyperemia"],"offsets":[[72,81]],"normalized":[{"db_name":"MESH","db_id":"D006940"}]},{"id":"9711","type":"Chemical","text":["dipyridamole"],"offsets":[[100,112]],"normalized":[{"db_name":"MESH","db_id":"D004176"}]},{"id":"9712","type":"Chemical","text":["thallium"],"offsets":[[113,121]],"normalized":[{"db_name":"MESH","db_id":"D013793"}]},{"id":"9713","type":"Chemical","text":["Dipyridamole"],"offsets":[[146,158]],"normalized":[{"db_name":"MESH","db_id":"D004176"}]},{"id":"9714","type":"Chemical","text":["thallium"],"offsets":[[159,167]],"normalized":[{"db_name":"MESH","db_id":"D013793"}]},{"id":"9715","type":"Disease","text":["peripheral 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{"id":"9784","document_id":"2355241","passages":[{"id":"9785","type":"title","text":["Cause of death among patients with Parkinson's disease: a rare mortality due to cerebral haemorrhage."],"offsets":[[0,101]]},{"id":"9786","type":"abstract","text":["Causes of death, with special reference to cerebral haemorrhage, among 240 patients with pathologically verified Parkinson's disease were investigated using the Annuals of the Pathological Autopsy Cases in Japan from 1981 to 1985. The leading causes of death were pneumonia and bronchitis (44.1%), malignant neoplasms (11.6%), heart diseases (4.1%), cerebral infarction (3.7%) and septicaemia (3.3%). Cerebral haemorrhage was the 11th most frequent cause of death, accounting for only 0.8% of deaths among the patients, whereas it was the 5th most common cause of death among the Japanese general population in 1985. The low incidence of cerebral haemorrhage as a cause of death in patients with Parkinson's disease may reflect the hypotensive effect of levodopa and a hypotensive mechanism due to reduced noradrenaline levels in the parkinsonian brain."],"offsets":[[102,955]]}],"entities":[{"id":"9787","type":"Disease","text":["death"],"offsets":[[9,14]],"normalized":[{"db_name":"MESH","db_id":"D003643"}]},{"id":"9788","type":"Disease","text":["Parkinson's disease"],"offsets":[[35,54]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"9789","type":"Disease","text":["cerebral haemorrhage"],"offsets":[[80,100]],"normalized":[{"db_name":"MESH","db_id":"D002543"}]},{"id":"9790","type":"Disease","text":["death"],"offsets":[[112,117]],"normalized":[{"db_name":"MESH","db_id":"D003643"}]},{"id":"9791","type":"Disease","text":["cerebral haemorrhage"],"offsets":[[145,165]],"normalized":[{"db_name":"MESH","db_id":"D002543"}]},{"id":"9792","type":"Disease","text":["Parkinson's disease"],"offsets":[[215,234]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"9793","type":"Disease","text":["death"],"offsets":[[355,360]],"normalized":[{"db_name":"MESH","db_id":"D003643"}]},{"id":"9794","type":"Disease","text":["pneumonia"],"offsets":[[366,375]],"normalized":[{"db_name":"MESH","db_id":"D011014"}]},{"id":"9795","type":"Disease","text":["bronchitis"],"offsets":[[380,390]],"normalized":[{"db_name":"MESH","db_id":"D001991"}]},{"id":"9796","type":"Disease","text":["neoplasms"],"offsets":[[410,419]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"9797","type":"Disease","text":["heart diseases"],"offsets":[[429,443]],"normalized":[{"db_name":"MESH","db_id":"D006331"}]},{"id":"9798","type":"Disease","text":["cerebral infarction"],"offsets":[[452,471]],"normalized":[{"db_name":"MESH","db_id":"D002544"}]},{"id":"9799","type":"Disease","text":["septicaemia"],"offsets":[[483,494]],"normalized":[{"db_name":"MESH","db_id":"D018805"}]},{"id":"9800","type":"Disease","text":["Cerebral haemorrhage"],"offsets":[[503,523]],"normalized":[{"db_name":"MESH","db_id":"D002543"}]},{"id":"9801","type":"Disease","text":["death"],"offsets":[[560,565]],"normalized":[{"db_name":"MESH","db_id":"D003643"}]},{"id":"9802","type":"Disease","text":["deaths"],"offsets":[[595,601]],"normalized":[{"db_name":"MESH","db_id":"D003643"}]},{"id":"9803","type":"Disease","text":["death"],"offsets":[[666,671]],"normalized":[{"db_name":"MESH","db_id":"D003643"}]},{"id":"9804","type":"Disease","text":["cerebral haemorrhage"],"offsets":[[740,760]],"normalized":[{"db_name":"MESH","db_id":"D002543"}]},{"id":"9805","type":"Disease","text":["death"],"offsets":[[775,780]],"normalized":[{"db_name":"MESH","db_id":"D003643"}]},{"id":"9806","type":"Disease","text":["Parkinson's disease"],"offsets":[[798,817]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"9807","type":"Disease","text":["hypotensive"],"offsets":[[834,845]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"9808","type":"Chemical","text":["levodopa"],"offsets":[[856,864]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"9809","type":"Disease","text":["hypotensive"],"offsets":[[871,882]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"9810","type":"Chemical","text":["noradrenaline"],"offsets":[[908,921]],"normalized":[{"db_name":"MESH","db_id":"D009638"}]},{"id":"9811","type":"Disease","text":["parkinsonian"],"offsets":[[936,948]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]}],"events":[],"coreferences":[],"relations":[{"id":"9812","type":"CID","arg1_id":"9808","arg2_id":"9807","normalized":[]},{"id":"9813","type":"CID","arg1_id":"9808","arg2_id":"9809","normalized":[]}]}
{"id":"9814","document_id":"2445283","passages":[{"id":"9815","type":"title","text":["Tolerance and antiviral effect of ribavirin in patients with Argentine hemorrhagic fever."],"offsets":[[0,89]]},{"id":"9816","type":"abstract","text":["Tolerance and antiviral effect of ribavirin was studied in 6 patients with Argentine hemorrhagic fever (AHF) of more than 8 days of evolution. Administration of ribavirin resulted in a neutralization of viremia and a drop of endogenous interferon titers. The average time of death was delayed. A reversible anemia was the only adverse effect observed. From these results, we conclude that ribavirin has an antiviral effect in advanced cases of AHF, and that anemia, the only secondary reaction observed, can be easily managed. The possible beneficial effect of ribavirin during the initial days of AHF is discussed."],"offsets":[[90,705]]}],"entities":[{"id":"9817","type":"Chemical","text":["ribavirin"],"offsets":[[34,43]],"normalized":[{"db_name":"MESH","db_id":"D012254"}]},{"id":"9818","type":"Disease","text":["Argentine hemorrhagic fever"],"offsets":[[61,88]],"normalized":[{"db_name":"MESH","db_id":"D006478"}]},{"id":"9819","type":"Chemical","text":["ribavirin"],"offsets":[[124,133]],"normalized":[{"db_name":"MESH","db_id":"D012254"}]},{"id":"9820","type":"Disease","text":["Argentine hemorrhagic fever"],"offsets":[[165,192]],"normalized":[{"db_name":"MESH","db_id":"D006478"}]},{"id":"9821","type":"Disease","text":["AHF"],"offsets":[[194,197]],"normalized":[{"db_name":"MESH","db_id":"D006478"}]},{"id":"9822","type":"Chemical","text":["ribavirin"],"offsets":[[251,260]],"normalized":[{"db_name":"MESH","db_id":"D012254"}]},{"id":"9823","type":"Disease","text":["viremia"],"offsets":[[293,300]],"normalized":[{"db_name":"MESH","db_id":"D014766"}]},{"id":"9824","type":"Disease","text":["death"],"offsets":[[365,370]],"normalized":[{"db_name":"MESH","db_id":"D003643"}]},{"id":"9825","type":"Disease","text":["anemia"],"offsets":[[397,403]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]},{"id":"9826","type":"Chemical","text":["ribavirin"],"offsets":[[479,488]],"normalized":[{"db_name":"MESH","db_id":"D012254"}]},{"id":"9827","type":"Disease","text":["AHF"],"offsets":[[534,537]],"normalized":[{"db_name":"MESH","db_id":"D006478"}]},{"id":"9828","type":"Disease","text":["anemia"],"offsets":[[548,554]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]},{"id":"9829","type":"Chemical","text":["ribavirin"],"offsets":[[651,660]],"normalized":[{"db_name":"MESH","db_id":"D012254"}]},{"id":"9830","type":"Disease","text":["AHF"],"offsets":[[688,691]],"normalized":[{"db_name":"MESH","db_id":"D006478"}]}],"events":[],"coreferences":[],"relations":[{"id":"9831","type":"CID","arg1_id":"9817","arg2_id":"9825","normalized":[]},{"id":"9832","type":"CID","arg1_id":"9817","arg2_id":"9828","normalized":[]},{"id":"9833","type":"CID","arg1_id":"9819","arg2_id":"9825","normalized":[]},{"id":"9834","type":"CID","arg1_id":"9819","arg2_id":"9828","normalized":[]},{"id":"9835","type":"CID","arg1_id":"9822","arg2_id":"9825","normalized":[]},{"id":"9836","type":"CID","arg1_id":"9822","arg2_id":"9828","normalized":[]},{"id":"9837","type":"CID","arg1_id":"9826","arg2_id":"9825","normalized":[]},{"id":"9838","type":"CID","arg1_id":"9826","arg2_id":"9828","normalized":[]},{"id":"9839","type":"CID","arg1_id":"9829","arg2_id":"9825","normalized":[]},{"id":"9840","type":"CID","arg1_id":"9829","arg2_id":"9828","normalized":[]}]}
{"id":"9841","document_id":"2950248","passages":[{"id":"9842","type":"title","text":["Dipyridamole-induced myocardial ischemia."],"offsets":[[0,41]]},{"id":"9843","type":"abstract","text":["Angina and ischemic electrocardiographic changes occurred after administration of oral dipyridamole in four patients awaiting urgent myocardial revascularization procedures. To our knowledge, this has not previously been reported as a side effect of preoperative dipyridamole therapy, although dipyridamole-induced myocardial ischemia has been demonstrated to occur in animals and humans with coronary artery disease. Epicardial coronary collateral vessels were demonstrated in all four patients; a coronary \"steal\" phenomenon may be the mechanism of the dipyridamole-induced ischemia observed."],"offsets":[[42,636]]}],"entities":[{"id":"9844","type":"Chemical","text":["Dipyridamole"],"offsets":[[0,12]],"normalized":[{"db_name":"MESH","db_id":"D004176"}]},{"id":"9845","type":"Disease","text":["myocardial ischemia"],"offsets":[[21,40]],"normalized":[{"db_name":"MESH","db_id":"D017202"}]},{"id":"9846","type":"Disease","text":["Angina"],"offsets":[[42,48]],"normalized":[{"db_name":"MESH","db_id":"D000787"}]},{"id":"9847","type":"Chemical","text":["dipyridamole"],"offsets":[[129,141]],"normalized":[{"db_name":"MESH","db_id":"D004176"}]},{"id":"9848","type":"Chemical","text":["dipyridamole"],"offsets":[[305,317]],"normalized":[{"db_name":"MESH","db_id":"D004176"}]},{"id":"9849","type":"Chemical","text":["dipyridamole"],"offsets":[[336,348]],"normalized":[{"db_name":"MESH","db_id":"D004176"}]},{"id":"9850","type":"Disease","text":["myocardial ischemia"],"offsets":[[357,376]],"normalized":[{"db_name":"MESH","db_id":"D017202"}]},{"id":"9851","type":"Disease","text":["coronary artery disease"],"offsets":[[435,458]],"normalized":[{"db_name":"MESH","db_id":"D003324"}]},{"id":"9852","type":"Chemical","text":["dipyridamole"],"offsets":[[597,609]],"normalized":[{"db_name":"MESH","db_id":"D004176"}]},{"id":"9853","type":"Disease","text":["ischemia"],"offsets":[[618,626]],"normalized":[{"db_name":"MESH","db_id":"D007511"}]}],"events":[],"coreferences":[],"relations":[{"id":"9854","type":"CID","arg1_id":"9844","arg2_id":"9846","normalized":[]},{"id":"9855","type":"CID","arg1_id":"9847","arg2_id":"9846","normalized":[]},{"id":"9856","type":"CID","arg1_id":"9848","arg2_id":"9846","normalized":[]},{"id":"9857","type":"CID","arg1_id":"9849","arg2_id":"9846","normalized":[]},{"id":"9858","type":"CID","arg1_id":"9852","arg2_id":"9846","normalized":[]}]}
{"id":"9859","document_id":"3015567","passages":[{"id":"9860","type":"title","text":["Inhibition of immunoreactive corticotropin-releasing factor secretion into the hypophysial-portal circulation by delayed glucocorticoid feedback."],"offsets":[[0,145]]},{"id":"9861","type":"abstract","text":["Nitroprusside-induced hypotension evokes ACTH secretion which is primarily mediated by enhanced secretion of immunoreactive corticotropin-releasing factor (irCRF) into the hypophysial-portal circulation. Portal plasma concentrations of neither arginine vasopressin nor oxytocin are significantly altered in this paradigm. Application of a delayed feedback signal, in the form of a 2-h systemic corticosterone infusion in urethane-anesthetized rats with pharmacological blockade of glucocorticoid synthesis, is without effect on the resting secretion of arginine vasopressin and oxytocin at any corticosterone feedback dose tested. Resting irCRF levels are suppressed only at the highest corticosterone infusion rate, which resulted in systemic corticosterone levels of 40 micrograms\/dl. Suppression of irCRF secretion in response to nitroprusside-induced hypotension is observed and occurs at a plasma corticosterone level between 8-12 micrograms\/dl. These studies provide further evidence for a strong central component of the delayed feedback process which is mediated by modulation of irCRF release."],"offsets":[[146,1248]]}],"entities":[{"id":"9862","type":"Chemical","text":["Nitroprusside"],"offsets":[[146,159]],"normalized":[{"db_name":"MESH","db_id":"D009599"}]},{"id":"9863","type":"Disease","text":["hypotension"],"offsets":[[168,179]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"9864","type":"Chemical","text":["arginine vasopressin"],"offsets":[[390,410]],"normalized":[{"db_name":"MESH","db_id":"D001127"}]},{"id":"9865","type":"Chemical","text":["oxytocin"],"offsets":[[415,423]],"normalized":[{"db_name":"MESH","db_id":"D010121"}]},{"id":"9866","type":"Chemical","text":["corticosterone"],"offsets":[[540,554]],"normalized":[{"db_name":"MESH","db_id":"D003345"}]},{"id":"9867","type":"Chemical","text":["urethane"],"offsets":[[567,575]],"normalized":[{"db_name":"MESH","db_id":"D014520"}]},{"id":"9868","type":"Chemical","text":["arginine vasopressin"],"offsets":[[699,719]],"normalized":[{"db_name":"MESH","db_id":"D001127"}]},{"id":"9869","type":"Chemical","text":["oxytocin"],"offsets":[[724,732]],"normalized":[{"db_name":"MESH","db_id":"D010121"}]},{"id":"9870","type":"Chemical","text":["corticosterone"],"offsets":[[740,754]],"normalized":[{"db_name":"MESH","db_id":"D003345"}]},{"id":"9871","type":"Chemical","text":["corticosterone"],"offsets":[[833,847]],"normalized":[{"db_name":"MESH","db_id":"D003345"}]},{"id":"9872","type":"Chemical","text":["corticosterone"],"offsets":[[890,904]],"normalized":[{"db_name":"MESH","db_id":"D003345"}]},{"id":"9873","type":"Chemical","text":["nitroprusside"],"offsets":[[979,992]],"normalized":[{"db_name":"MESH","db_id":"D009599"}]},{"id":"9874","type":"Disease","text":["hypotension"],"offsets":[[1001,1012]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"9875","type":"Chemical","text":["corticosterone"],"offsets":[[1048,1062]],"normalized":[{"db_name":"MESH","db_id":"D003345"}]}],"events":[],"coreferences":[],"relations":[{"id":"9876","type":"CID","arg1_id":"9862","arg2_id":"9863","normalized":[]},{"id":"9877","type":"CID","arg1_id":"9862","arg2_id":"9874","normalized":[]},{"id":"9878","type":"CID","arg1_id":"9873","arg2_id":"9863","normalized":[]},{"id":"9879","type":"CID","arg1_id":"9873","arg2_id":"9874","normalized":[]}]}
{"id":"9880","document_id":"3031535","passages":[{"id":"9881","type":"title","text":["Noradrenergic involvement in catalepsy induced by delta 9-tetrahydrocannabinol."],"offsets":[[0,79]]},{"id":"9882","type":"abstract","text":["In order to elucidate the role of the catecholaminergic system in the cataleptogenic effect of delta 9-tetrahydrocannabinol (THC), the effect of pretreatment with 6-hydroxydopamine (6-OHDA) or with desipramine and 6-OHDA and lesions of the locus coeruleus were investigated in rats. The cataleptogenic effect of THC was significantly reduced in rats treated with 6-OHDA and in rats with lesions of the locus coeruleus but not in rats treated with desipramine and 6-OHDA, as compared with control rats. On the contrary, the cataleptogenic effect of haloperidol was significantly reduced in rats treated with desipramine and 6-OHDA but not in rats treated with 6-OHDA or in rats with lesions of the locus coeruleus. These results indicate that noradrenergic neurons have an important role in the manifestation of catalepsy induced by THC, whereas dopaminergic neurons are important in catalepsy induced by haloperidol."],"offsets":[[80,996]]}],"entities":[{"id":"9883","type":"Disease","text":["catalepsy"],"offsets":[[29,38]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"9884","type":"Chemical","text":["delta 9-tetrahydrocannabinol"],"offsets":[[50,78]],"normalized":[{"db_name":"MESH","db_id":"D013759"}]},{"id":"9885","type":"Chemical","text":["delta 9-tetrahydrocannabinol"],"offsets":[[175,203]],"normalized":[{"db_name":"MESH","db_id":"D013759"}]},{"id":"9886","type":"Chemical","text":["THC"],"offsets":[[205,208]],"normalized":[{"db_name":"MESH","db_id":"D013759"}]},{"id":"9887","type":"Chemical","text":["6-hydroxydopamine"],"offsets":[[243,260]],"normalized":[{"db_name":"MESH","db_id":"D016627"}]},{"id":"9888","type":"Chemical","text":["6-OHDA"],"offsets":[[262,268]],"normalized":[{"db_name":"MESH","db_id":"D016627"}]},{"id":"9889","type":"Chemical","text":["desipramine"],"offsets":[[278,289]],"normalized":[{"db_name":"MESH","db_id":"D003891"}]},{"id":"9890","type":"Chemical","text":["6-OHDA"],"offsets":[[294,300]],"normalized":[{"db_name":"MESH","db_id":"D016627"}]},{"id":"9891","type":"Chemical","text":["THC"],"offsets":[[392,395]],"normalized":[{"db_name":"MESH","db_id":"D013759"}]},{"id":"9892","type":"Chemical","text":["6-OHDA"],"offsets":[[443,449]],"normalized":[{"db_name":"MESH","db_id":"D016627"}]},{"id":"9893","type":"Chemical","text":["desipramine"],"offsets":[[527,538]],"normalized":[{"db_name":"MESH","db_id":"D003891"}]},{"id":"9894","type":"Chemical","text":["6-OHDA"],"offsets":[[543,549]],"normalized":[{"db_name":"MESH","db_id":"D016627"}]},{"id":"9895","type":"Chemical","text":["haloperidol"],"offsets":[[628,639]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"9896","type":"Chemical","text":["desipramine"],"offsets":[[687,698]],"normalized":[{"db_name":"MESH","db_id":"D003891"}]},{"id":"9897","type":"Chemical","text":["6-OHDA"],"offsets":[[703,709]],"normalized":[{"db_name":"MESH","db_id":"D016627"}]},{"id":"9898","type":"Chemical","text":["6-OHDA"],"offsets":[[739,745]],"normalized":[{"db_name":"MESH","db_id":"D016627"}]},{"id":"9899","type":"Disease","text":["catalepsy"],"offsets":[[891,900]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"9900","type":"Chemical","text":["THC"],"offsets":[[912,915]],"normalized":[{"db_name":"MESH","db_id":"D013759"}]},{"id":"9901","type":"Disease","text":["catalepsy"],"offsets":[[963,972]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"9902","type":"Chemical","text":["haloperidol"],"offsets":[[984,995]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]}],"events":[],"coreferences":[],"relations":[{"id":"9903","type":"CID","arg1_id":"9895","arg2_id":"9883","normalized":[]},{"id":"9904","type":"CID","arg1_id":"9895","arg2_id":"9899","normalized":[]},{"id":"9905","type":"CID","arg1_id":"9895","arg2_id":"9901","normalized":[]},{"id":"9906","type":"CID","arg1_id":"9902","arg2_id":"9883","normalized":[]},{"id":"9907","type":"CID","arg1_id":"9902","arg2_id":"9899","normalized":[]},{"id":"9908","type":"CID","arg1_id":"9902","arg2_id":"9901","normalized":[]},{"id":"9909","type":"CID","arg1_id":"9884","arg2_id":"9883","normalized":[]},{"id":"9910","type":"CID","arg1_id":"9884","arg2_id":"9899","normalized":[]},{"id":"9911","type":"CID","arg1_id":"9884","arg2_id":"9901","normalized":[]},{"id":"9912","type":"CID","arg1_id":"9885","arg2_id":"9883","normalized":[]},{"id":"9913","type":"CID","arg1_id":"9885","arg2_id":"9899","normalized":[]},{"id":"9914","type":"CID","arg1_id":"9885","arg2_id":"9901","normalized":[]},{"id":"9915","type":"CID","arg1_id":"9886","arg2_id":"9883","normalized":[]},{"id":"9916","type":"CID","arg1_id":"9886","arg2_id":"9899","normalized":[]},{"id":"9917","type":"CID","arg1_id":"9886","arg2_id":"9901","normalized":[]},{"id":"9918","type":"CID","arg1_id":"9891","arg2_id":"9883","normalized":[]},{"id":"9919","type":"CID","arg1_id":"9891","arg2_id":"9899","normalized":[]},{"id":"9920","type":"CID","arg1_id":"9891","arg2_id":"9901","normalized":[]},{"id":"9921","type":"CID","arg1_id":"9900","arg2_id":"9883","normalized":[]},{"id":"9922","type":"CID","arg1_id":"9900","arg2_id":"9899","normalized":[]},{"id":"9923","type":"CID","arg1_id":"9900","arg2_id":"9901","normalized":[]}]}
{"id":"9924","document_id":"3125768","passages":[{"id":"9925","type":"title","text":["Intracranial pressure increases during alfentanil-induced rigidity."],"offsets":[[0,67]]},{"id":"9926","type":"abstract","text":["Intracranial pressure (ICP) was measured during alfentanil-induced rigidity in rats. Ten rats had arterial, central venous (CVP), and subdural cannulae inserted under halothane anesthesia. The animals were mechanically ventilated to achieve normocarbia (PCO2 = 42 +\/- 1 mmHg, mean +\/- SE). Following instrumentation, halothane was discontinued and alfentanil (125 mu\/kg) administered iv during emergence from halothane anesthesia. In the five rats that developed somatic rigidity, ICP and CVP increased significantly above baseline (delta ICP 7.5 +\/- 1.0 mmHg, delta CVP 5.9 +\/- 1.3 mmHg). These variables returned to baseline when rigidity was abolished with metocurine. In five rats that did not become rigid, ICP and CVP did not change following alfentanil. These observations suggest that rigidity should be prevented when alfentanil, and, presumably, other opiates, are used in the anesthetic management of patients with ICP problems."],"offsets":[[68,1007]]}],"entities":[{"id":"9927","type":"Chemical","text":["alfentanil"],"offsets":[[39,49]],"normalized":[{"db_name":"MESH","db_id":"D015760"}]},{"id":"9928","type":"Disease","text":["rigidity"],"offsets":[[58,66]],"normalized":[{"db_name":"MESH","db_id":"D009127"}]},{"id":"9929","type":"Chemical","text":["alfentanil"],"offsets":[[116,126]],"normalized":[{"db_name":"MESH","db_id":"D015760"}]},{"id":"9930","type":"Disease","text":["rigidity"],"offsets":[[135,143]],"normalized":[{"db_name":"MESH","db_id":"D009127"}]},{"id":"9931","type":"Chemical","text":["halothane"],"offsets":[[235,244]],"normalized":[{"db_name":"MESH","db_id":"D006221"}]},{"id":"9932","type":"Chemical","text":["halothane"],"offsets":[[385,394]],"normalized":[{"db_name":"MESH","db_id":"D006221"}]},{"id":"9933","type":"Chemical","text":["alfentanil"],"offsets":[[416,426]],"normalized":[{"db_name":"MESH","db_id":"D015760"}]},{"id":"9934","type":"Chemical","text":["halothane"],"offsets":[[477,486]],"normalized":[{"db_name":"MESH","db_id":"D006221"}]},{"id":"9935","type":"Disease","text":["somatic rigidity"],"offsets":[[531,547]],"normalized":[{"db_name":"MESH","db_id":"D009127"}]},{"id":"9936","type":"Disease","text":["rigidity"],"offsets":[[700,708]],"normalized":[{"db_name":"MESH","db_id":"D009127"}]},{"id":"9937","type":"Chemical","text":["metocurine"],"offsets":[[728,738]],"normalized":[{"db_name":"MESH","db_id":"C032943"}]},{"id":"9938","type":"Chemical","text":["alfentanil"],"offsets":[[817,827]],"normalized":[{"db_name":"MESH","db_id":"D015760"}]},{"id":"9939","type":"Disease","text":["rigidity"],"offsets":[[861,869]],"normalized":[{"db_name":"MESH","db_id":"D009127"}]},{"id":"9940","type":"Chemical","text":["alfentanil"],"offsets":[[895,905]],"normalized":[{"db_name":"MESH","db_id":"D015760"}]}],"events":[],"coreferences":[],"relations":[{"id":"9941","type":"CID","arg1_id":"9927","arg2_id":"9928","normalized":[]},{"id":"9942","type":"CID","arg1_id":"9927","arg2_id":"9930","normalized":[]},{"id":"9943","type":"CID","arg1_id":"9927","arg2_id":"9935","normalized":[]},{"id":"9944","type":"CID","arg1_id":"9927","arg2_id":"9936","normalized":[]},{"id":"9945","type":"CID","arg1_id":"9927","arg2_id":"9939","normalized":[]},{"id":"9946","type":"CID","arg1_id":"9929","arg2_id":"9928","normalized":[]},{"id":"9947","type":"CID","arg1_id":"9929","arg2_id":"9930","normalized":[]},{"id":"9948","type":"CID","arg1_id":"9929","arg2_id":"9935","normalized":[]},{"id":"9949","type":"CID","arg1_id":"9929","arg2_id":"9936","normalized":[]},{"id":"9950","type":"CID","arg1_id":"9929","arg2_id":"9939","normalized":[]},{"id":"9951","type":"CID","arg1_id":"9933","arg2_id":"9928","normalized":[]},{"id":"9952","type":"CID","arg1_id":"9933","arg2_id":"9930","normalized":[]},{"id":"9953","type":"CID","arg1_id":"9933","arg2_id":"9935","normalized":[]},{"id":"9954","type":"CID","arg1_id":"9933","arg2_id":"9936","normalized":[]},{"id":"9955","type":"CID","arg1_id":"9933","arg2_id":"9939","normalized":[]},{"id":"9956","type":"CID","arg1_id":"9938","arg2_id":"9928","normalized":[]},{"id":"9957","type":"CID","arg1_id":"9938","arg2_id":"9930","normalized":[]},{"id":"9958","type":"CID","arg1_id":"9938","arg2_id":"9935","normalized":[]},{"id":"9959","type":"CID","arg1_id":"9938","arg2_id":"9936","normalized":[]},{"id":"9960","type":"CID","arg1_id":"9938","arg2_id":"9939","normalized":[]},{"id":"9961","type":"CID","arg1_id":"9940","arg2_id":"9928","normalized":[]},{"id":"9962","type":"CID","arg1_id":"9940","arg2_id":"9930","normalized":[]},{"id":"9963","type":"CID","arg1_id":"9940","arg2_id":"9935","normalized":[]},{"id":"9964","type":"CID","arg1_id":"9940","arg2_id":"9936","normalized":[]},{"id":"9965","type":"CID","arg1_id":"9940","arg2_id":"9939","normalized":[]}]}
{"id":"9966","document_id":"3187073","passages":[{"id":"9967","type":"title","text":["Adverse cardiac effects during induction chemotherapy treatment with cis-platin and 5-fluorouracil."],"offsets":[[0,99]]},{"id":"9968","type":"abstract","text":["Survival for patients with advanced head and neck carcinoma and esophageal carcinoma is poor with radiotherapy and\/or surgery. Obviously, there is a need for effective chemotherapy. In the present study, cis-platin (80-120 mg\/m2BSA) and 5-FU (1000 mg\/m2BSA daily as a continuous infusion during 5 days) were given to 76 patients before radiotherapy and surgery. The aim of the study was to clarify the incidence and severity of adverse cardiac effects to this treatment. Before treatment all patients had a cardiac evaluation and during treatment serial ECG recordings were performed. In the pre-treatment evaluation, signs of cardiovascular disease were found in 33 patients (43%). During treatment, adverse cardiac effects were observed in 14 patients (18%). The mean age of these patients was the same as for the entire group, 64 years. The incidence of cardiotoxicity was not higher in patients with signs of cardiovascular disease than in those without in the pre-treatment evaluation. The most common signs of cardiotoxicity were chest pain, ST-T wave changes and atrial fibrillation. This was followed by ventricular fibrillation in one patient and sudden death in another. It is concluded that patients on 5-FU treatment should be under close supervision and that the treatment should be discontinued if chest pain or tachyarrhythmia is observed."],"offsets":[[100,1454]]}],"entities":[{"id":"9969","type":"Chemical","text":["cis-platin"],"offsets":[[69,79]],"normalized":[{"db_name":"MESH","db_id":"D002945"}]},{"id":"9970","type":"Chemical","text":["5-fluorouracil"],"offsets":[[84,98]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"9971","type":"Disease","text":["head and neck carcinoma"],"offsets":[[136,159]],"normalized":[{"db_name":"MESH","db_id":"D006258"}]},{"id":"9972","type":"Disease","text":["esophageal carcinoma"],"offsets":[[164,184]],"normalized":[{"db_name":"MESH","db_id":"D004938"}]},{"id":"9973","type":"Chemical","text":["cis-platin"],"offsets":[[304,314]],"normalized":[{"db_name":"MESH","db_id":"D002945"}]},{"id":"9974","type":"Chemical","text":["5-FU"],"offsets":[[337,341]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"9975","type":"Disease","text":["cardiovascular disease"],"offsets":[[727,749]],"normalized":[{"db_name":"MESH","db_id":"D002318"}]},{"id":"9976","type":"Disease","text":["cardiotoxicity"],"offsets":[[957,971]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"9977","type":"Disease","text":["cardiovascular disease"],"offsets":[[1013,1035]],"normalized":[{"db_name":"MESH","db_id":"D002318"}]},{"id":"9978","type":"Disease","text":["cardiotoxicity"],"offsets":[[1116,1130]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"9979","type":"Disease","text":["chest pain"],"offsets":[[1136,1146]],"normalized":[{"db_name":"MESH","db_id":"D002637"}]},{"id":"9980","type":"Disease","text":["atrial fibrillation"],"offsets":[[1170,1189]],"normalized":[{"db_name":"MESH","db_id":"D001281"}]},{"id":"9981","type":"Disease","text":["ventricular fibrillation"],"offsets":[[1212,1236]],"normalized":[{"db_name":"MESH","db_id":"D014693"}]},{"id":"9982","type":"Disease","text":["sudden death"],"offsets":[[1256,1268]],"normalized":[{"db_name":"MESH","db_id":"D003645"}]},{"id":"9983","type":"Chemical","text":["5-FU"],"offsets":[[1314,1318]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"9984","type":"Disease","text":["chest pain"],"offsets":[[1412,1422]],"normalized":[{"db_name":"MESH","db_id":"D002637"}]},{"id":"9985","type":"Disease","text":["tachyarrhythmia"],"offsets":[[1426,1441]],"normalized":[{"db_name":"MESH","db_id":"D013610"}]}],"events":[],"coreferences":[],"relations":[{"id":"9986","type":"CID","arg1_id":"9969","arg2_id":"9975","normalized":[]},{"id":"9987","type":"CID","arg1_id":"9969","arg2_id":"9977","normalized":[]},{"id":"9988","type":"CID","arg1_id":"9973","arg2_id":"9975","normalized":[]},{"id":"9989","type":"CID","arg1_id":"9973","arg2_id":"9977","normalized":[]},{"id":"9990","type":"CID","arg1_id":"9970","arg2_id":"9981","normalized":[]},{"id":"9991","type":"CID","arg1_id":"9974","arg2_id":"9981","normalized":[]},{"id":"9992","type":"CID","arg1_id":"9983","arg2_id":"9981","normalized":[]},{"id":"9993","type":"CID","arg1_id":"9970","arg2_id":"9979","normalized":[]},{"id":"9994","type":"CID","arg1_id":"9970","arg2_id":"9984","normalized":[]},{"id":"9995","type":"CID","arg1_id":"9974","arg2_id":"9979","normalized":[]},{"id":"9996","type":"CID","arg1_id":"9974","arg2_id":"9984","normalized":[]},{"id":"9997","type":"CID","arg1_id":"9983","arg2_id":"9979","normalized":[]},{"id":"9998","type":"CID","arg1_id":"9983","arg2_id":"9984","normalized":[]},{"id":"9999","type":"CID","arg1_id":"9970","arg2_id":"9980","normalized":[]},{"id":"10000","type":"CID","arg1_id":"9974","arg2_id":"9980","normalized":[]},{"id":"10001","type":"CID","arg1_id":"9983","arg2_id":"9980","normalized":[]},{"id":"10002","type":"CID","arg1_id":"9969","arg2_id":"9980","normalized":[]},{"id":"10003","type":"CID","arg1_id":"9973","arg2_id":"9980","normalized":[]},{"id":"10004","type":"CID","arg1_id":"9970","arg2_id":"9975","normalized":[]},{"id":"10005","type":"CID","arg1_id":"9970","arg2_id":"9977","normalized":[]},{"id":"10006","type":"CID","arg1_id":"9974","arg2_id":"9975","normalized":[]},{"id":"10007","type":"CID","arg1_id":"9974","arg2_id":"9977","normalized":[]},{"id":"10008","type":"CID","arg1_id":"9983","arg2_id":"9975","normalized":[]},{"id":"10009","type":"CID","arg1_id":"9983","arg2_id":"9977","normalized":[]},{"id":"10010","type":"CID","arg1_id":"9969","arg2_id":"9981","normalized":[]},{"id":"10011","type":"CID","arg1_id":"9973","arg2_id":"9981","normalized":[]},{"id":"10012","type":"CID","arg1_id":"9969","arg2_id":"9979","normalized":[]},{"id":"10013","type":"CID","arg1_id":"9969","arg2_id":"9984","normalized":[]},{"id":"10014","type":"CID","arg1_id":"9973","arg2_id":"9979","normalized":[]},{"id":"10015","type":"CID","arg1_id":"9973","arg2_id":"9984","normalized":[]}]}
{"id":"10016","document_id":"3371379","passages":[{"id":"10017","type":"title","text":["Verapamil-induced carbamazepine neurotoxicity. A report of two cases."],"offsets":[[0,69]]},{"id":"10018","type":"abstract","text":["Two patients with signs of carbamazepine neurotoxicity after combined treatment with verapamil showed complete recovery after discontinuation of the calcium entry blocker. Use of verapamil in combination with carbamazepine should either be avoided or prescribed only with appropriate adjustment of the carbamazepine dose (usually reduction of the carbamazepine dose by one half)."],"offsets":[[70,449]]}],"entities":[{"id":"10019","type":"Chemical","text":["Verapamil"],"offsets":[[0,9]],"normalized":[{"db_name":"MESH","db_id":"D014700"}]},{"id":"10020","type":"Chemical","text":["carbamazepine"],"offsets":[[18,31]],"normalized":[{"db_name":"MESH","db_id":"D002220"}]},{"id":"10021","type":"Disease","text":["neurotoxicity"],"offsets":[[32,45]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"10022","type":"Chemical","text":["carbamazepine"],"offsets":[[97,110]],"normalized":[{"db_name":"MESH","db_id":"D002220"}]},{"id":"10023","type":"Disease","text":["neurotoxicity"],"offsets":[[111,124]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"10024","type":"Chemical","text":["verapamil"],"offsets":[[155,164]],"normalized":[{"db_name":"MESH","db_id":"D014700"}]},{"id":"10025","type":"Chemical","text":["calcium"],"offsets":[[219,226]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"10026","type":"Chemical","text":["verapamil"],"offsets":[[249,258]],"normalized":[{"db_name":"MESH","db_id":"D014700"}]},{"id":"10027","type":"Chemical","text":["carbamazepine"],"offsets":[[279,292]],"normalized":[{"db_name":"MESH","db_id":"D002220"}]},{"id":"10028","type":"Chemical","text":["carbamazepine"],"offsets":[[372,385]],"normalized":[{"db_name":"MESH","db_id":"D002220"}]},{"id":"10029","type":"Chemical","text":["carbamazepine"],"offsets":[[417,430]],"normalized":[{"db_name":"MESH","db_id":"D002220"}]}],"events":[],"coreferences":[],"relations":[{"id":"10030","type":"CID","arg1_id":"10019","arg2_id":"10021","normalized":[]},{"id":"10031","type":"CID","arg1_id":"10019","arg2_id":"10023","normalized":[]},{"id":"10032","type":"CID","arg1_id":"10024","arg2_id":"10021","normalized":[]},{"id":"10033","type":"CID","arg1_id":"10024","arg2_id":"10023","normalized":[]},{"id":"10034","type":"CID","arg1_id":"10026","arg2_id":"10021","normalized":[]},{"id":"10035","type":"CID","arg1_id":"10026","arg2_id":"10023","normalized":[]},{"id":"10036","type":"CID","arg1_id":"10020","arg2_id":"10021","normalized":[]},{"id":"10037","type":"CID","arg1_id":"10020","arg2_id":"10023","normalized":[]},{"id":"10038","type":"CID","arg1_id":"10022","arg2_id":"10021","normalized":[]},{"id":"10039","type":"CID","arg1_id":"10022","arg2_id":"10023","normalized":[]},{"id":"10040","type":"CID","arg1_id":"10027","arg2_id":"10021","normalized":[]},{"id":"10041","type":"CID","arg1_id":"10027","arg2_id":"10023","normalized":[]},{"id":"10042","type":"CID","arg1_id":"10028","arg2_id":"10021","normalized":[]},{"id":"10043","type":"CID","arg1_id":"10028","arg2_id":"10023","normalized":[]},{"id":"10044","type":"CID","arg1_id":"10029","arg2_id":"10021","normalized":[]},{"id":"10045","type":"CID","arg1_id":"10029","arg2_id":"10023","normalized":[]}]}
{"id":"10046","document_id":"3503576","passages":[{"id":"10047","type":"title","text":["Serial studies of auditory neurotoxicity in patients receiving deferoxamine therapy."],"offsets":[[0,84]]},{"id":"10048","type":"abstract","text":["Visual and auditory neurotoxicity was previously documented in 42 of 89 patients with transfusion-dependent anemia who were receiving iron chelation therapy with daily subcutaneous deferoxamine. Twenty-two patients in the affected group had abnormal audiograms with deficits mostly in the high frequency range of 4,000 to 8,000 Hz and in the hearing threshold levels of 30 to 100 decibels. When deferoxamine therapy was discontinued and serial studies were performed, audiograms in seven cases reverted to normal or near normal within two to three weeks, and nine of 13 patients with symptoms became asymptomatic. Audiograms from 15 patients remained abnormal and four patients required hearing aids because of permanent disability. Since 18 of the 22 patients were initially receiving deferoxamine doses in excess of the commonly recommended 50 mg\/kg per dose, therapy was restarted with lower doses, usually 50 mg\/kg per dose or less depending on the degree of auditory abnormality, and with the exception of two cases no further toxicity was demonstrated. Auditory deterioration and improvement, demonstrated serially in individual patients receiving and not receiving deferoxamine, respectively, provided convincing evidence for a cause-and-effect relation between deferoxamine administration and ototoxicity. Based on these data, a plan of management was developed that allows effective yet safe administration of deferoxamine. A dose of 50 mg\/kg is recommended in those without audiogram abnormalities. With mild toxicity, a reduction to 30 or 40 mg\/kg per dose should result in a reversal of the abnormal results to normal within four weeks. Moderate abnormalities require a reduction of deferoxamine to 25 mg\/kg per dose with careful monitoring. In those with symptoms of hearing loss, the drug should be stopped for four weeks, and when the audiogram is stable or improved, therapy should be restarted at 10 to 25 mg\/kg per dose. Serial audiograms should be performed every six months in those without problems and more frequently in young patients with normal serum ferritin values and in those with auditory dysfunction."],"offsets":[[85,2216]]}],"entities":[{"id":"10049","type":"Disease","text":["auditory neurotoxicity"],"offsets":[[18,40]],"normalized":[{"db_name":"MESH","db_id":"D006311"}]},{"id":"10050","type":"Chemical","text":["deferoxamine"],"offsets":[[63,75]],"normalized":[{"db_name":"MESH","db_id":"D003676"}]},{"id":"10051","type":"Disease","text":["Visual and auditory neurotoxicity"],"offsets":[[85,118]],"normalized":[{"db_name":"MESH","db_id":"D014786"},{"db_name":"MESH","db_id":"D006311"}]},{"id":"10052","type":"Disease","text":["Visual","neurotoxicity"],"offsets":[[85,91],[105,118]],"normalized":[{"db_name":"MESH","db_id":"D014786"}]},{"id":"10053","type":"Disease","text":["auditory 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{"id":"10095","document_id":"3560095","passages":[{"id":"10096","type":"title","text":["Flurbiprofen in the treatment of juvenile rheumatoid arthritis."],"offsets":[[0,63]]},{"id":"10097","type":"abstract","text":["Thirty-four patients with juvenile rheumatoid arthritis, who were treated with flurbiprofen at a maximum dose of 4 mg\/kg\/day, had statistically significant decreases from baseline in 6 arthritis indices after 12 weeks of treatment. Improvements were seen in the number of tender joints, the severity of swelling and tenderness, the time of walk 50 feet, the duration of morning stiffness and the circumference of the left knee. The most frequently observed side effect was fecal occult blood (25% of patients); however, there was no other evidence of gastrointestinal (GI) bleeding in these patients. One patient was prematurely discontinued from the study for severe headache and abdominal pain. Most side effects were mild and related to the GI tract."],"offsets":[[64,817]]}],"entities":[{"id":"10098","type":"Chemical","text":["Flurbiprofen"],"offsets":[[0,12]],"normalized":[{"db_name":"MESH","db_id":"D005480"}]},{"id":"10099","type":"Disease","text":["juvenile rheumatoid arthritis"],"offsets":[[33,62]],"normalized":[{"db_name":"MESH","db_id":"D001171"}]},{"id":"10100","type":"Disease","text":["juvenile rheumatoid arthritis"],"offsets":[[90,119]],"normalized":[{"db_name":"MESH","db_id":"D001171"}]},{"id":"10101","type":"Chemical","text":["flurbiprofen"],"offsets":[[143,155]],"normalized":[{"db_name":"MESH","db_id":"D005480"}]},{"id":"10102","type":"Disease","text":["arthritis"],"offsets":[[249,258]],"normalized":[{"db_name":"MESH","db_id":"D001168"}]},{"id":"10103","type":"Disease","text":["tender joints"],"offsets":[[336,349]],"normalized":[]},{"id":"10104","type":"Disease","text":["swelling"],"offsets":[[367,375]],"normalized":[{"db_name":"MESH","db_id":"D004487"}]},{"id":"10105","type":"Disease","text":["tenderness"],"offsets":[[380,390]],"normalized":[]},{"id":"10106","type":"Disease","text":["morning stiffness"],"offsets":[[434,451]],"normalized":[]},{"id":"10107","type":"Disease","text":["fecal occult blood"],"offsets":[[537,555]],"normalized":[]},{"id":"10108","type":"Disease","text":["gastrointestinal (GI) bleeding"],"offsets":[[615,645]],"normalized":[{"db_name":"MESH","db_id":"D006471"}]},{"id":"10109","type":"Disease","text":["headache"],"offsets":[[732,740]],"normalized":[{"db_name":"MESH","db_id":"D006261"}]},{"id":"10110","type":"Disease","text":["abdominal pain"],"offsets":[[745,759]],"normalized":[{"db_name":"MESH","db_id":"D015746"}]}],"events":[],"coreferences":[],"relations":[{"id":"10111","type":"CID","arg1_id":"10098","arg2_id":"10109","normalized":[]},{"id":"10112","type":"CID","arg1_id":"10101","arg2_id":"10109","normalized":[]},{"id":"10113","type":"CID","arg1_id":"10098","arg2_id":"10108","normalized":[]},{"id":"10114","type":"CID","arg1_id":"10101","arg2_id":"10108","normalized":[]},{"id":"10115","type":"CID","arg1_id":"10098","arg2_id":"10110","normalized":[]},{"id":"10116","type":"CID","arg1_id":"10101","arg2_id":"10110","normalized":[]}]}
{"id":"10117","document_id":"3714122","passages":[{"id":"10118","type":"title","text":["The correlation between neurotoxic esterase inhibition and mipafox-induced neuropathic damage in rats."],"offsets":[[0,102]]},{"id":"10119","type":"abstract","text":["The correlation between neuropathic damage and inhibition of neurotoxic esterase or neuropathy target enzyme (NTE) was examined in rats acutely exposed to Mipafox (N, N'-diisopropylphosphorodiamidofluoridate), a neurotoxic organophosphate. Brain and spinal cord NTE activities were measured in Long-Evans male rats 1 hr post-exposure to various dosages of Mipafox (ip, 1-15 mg\/kg). These data were correlated with histologically scored cervical cord damage in a separate group of similarly dosed rats sampled 14-21 days post-exposure. Those dosages (greater than or equal to 10 mg\/kg) that inhibited mean NTE activity in the spinal cord greater than or equal to 73% and brain greater than or equal to 67% of control values produced severe (greater than or equal to 3) cervical cord pathology in 85% of the rats. In contrast, dosages of Mipafox (less than or equal to 5 mg\/kg) which inhibited mean NTE activity in spinal cord less than or equal to 61% and brain less than or equal to 60% produced this degree of cord damage in only 9% of the animals. These data indicate that a critical percentage of NTE inhibition in brain and spinal cord sampled shortly after Mipafox exposure can predict neuropathic damage in rats several weeks later."],"offsets":[[103,1341]]}],"entities":[{"id":"10120","type":"Disease","text":["neurotoxic"],"offsets":[[24,34]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"10121","type":"Chemical","text":["mipafox"],"offsets":[[59,66]],"normalized":[{"db_name":"MESH","db_id":"C005238"}]},{"id":"10122","type":"Disease","text":["neuropathic damage"],"offsets":[[75,93]],"normalized":[{"db_name":"MESH","db_id":"D009422"}]},{"id":"10123","type":"Disease","text":["neuropathic damage"],"offsets":[[127,145]],"normalized":[{"db_name":"MESH","db_id":"D009422"}]},{"id":"10124","type":"Disease","text":["neurotoxic"],"offsets":[[164,174]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"10125","type":"Disease","text":["neuropathy"],"offsets":[[187,197]],"normalized":[{"db_name":"MESH","db_id":"D009422"}]},{"id":"10126","type":"Chemical","text":["Mipafox"],"offsets":[[258,265]],"normalized":[{"db_name":"MESH","db_id":"C005238"}]},{"id":"10127","type":"Chemical","text":["N, N'-diisopropylphosphorodiamidofluoridate"],"offsets":[[267,310]],"normalized":[{"db_name":"MESH","db_id":"C005238"}]},{"id":"10128","type":"Disease","text":["neurotoxic"],"offsets":[[315,325]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"10129","type":"Chemical","text":["organophosphate"],"offsets":[[326,341]],"normalized":[{"db_name":"MESH","db_id":"D010755"}]},{"id":"10130","type":"Chemical","text":["Mipafox"],"offsets":[[459,466]],"normalized":[{"db_name":"MESH","db_id":"C005238"}]},{"id":"10131","type":"Disease","text":["cord damage"],"offsets":[[548,559]],"normalized":[{"db_name":"MESH","db_id":"D013118"}]},{"id":"10132","type":"Chemical","text":["Mipafox"],"offsets":[[939,946]],"normalized":[{"db_name":"MESH","db_id":"C005238"}]},{"id":"10133","type":"Disease","text":["cord damage"],"offsets":[[1114,1125]],"normalized":[{"db_name":"MESH","db_id":"D013118"}]},{"id":"10134","type":"Chemical","text":["Mipafox"],"offsets":[[1265,1272]],"normalized":[{"db_name":"MESH","db_id":"C005238"}]},{"id":"10135","type":"Disease","text":["neuropathic damage"],"offsets":[[1294,1312]],"normalized":[{"db_name":"MESH","db_id":"D009422"}]}],"events":[],"coreferences":[],"relations":[{"id":"10136","type":"CID","arg1_id":"10121","arg2_id":"10131","normalized":[]},{"id":"10137","type":"CID","arg1_id":"10121","arg2_id":"10133","normalized":[]},{"id":"10138","type":"CID","arg1_id":"10126","arg2_id":"10131","normalized":[]},{"id":"10139","type":"CID","arg1_id":"10126","arg2_id":"10133","normalized":[]},{"id":"10140","type":"CID","arg1_id":"10127","arg2_id":"10131","normalized":[]},{"id":"10141","type":"CID","arg1_id":"10127","arg2_id":"10133","normalized":[]},{"id":"10142","type":"CID","arg1_id":"10130","arg2_id":"10131","normalized":[]},{"id":"10143","type":"CID","arg1_id":"10130","arg2_id":"10133","normalized":[]},{"id":"10144","type":"CID","arg1_id":"10132","arg2_id":"10131","normalized":[]},{"id":"10145","type":"CID","arg1_id":"10132","arg2_id":"10133","normalized":[]},{"id":"10146","type":"CID","arg1_id":"10134","arg2_id":"10131","normalized":[]},{"id":"10147","type":"CID","arg1_id":"10134","arg2_id":"10133","normalized":[]}]}
{"id":"10148","document_id":"3828020","passages":[{"id":"10149","type":"title","text":["Cerebral infarction with a single oral dose of phenylpropanolamine."],"offsets":[[0,67]]},{"id":"10150","type":"abstract","text":["Phenylpropanolamine (PPA), a synthetic sympathomimetic that is structurally similar to amphetamine, is available over the counter in anorectics, nasal congestants, and cold preparations. Its prolonged use or overuse has been associated with seizures, intracerebral hemorrhage, neuropsychiatric symptoms, and nonhemorrhagic cerebral infarction. We report the case of a young woman who suffered a cerebral infarction after taking a single oral dose of PPA."],"offsets":[[68,522]]}],"entities":[{"id":"10151","type":"Disease","text":["Cerebral infarction"],"offsets":[[0,19]],"normalized":[{"db_name":"MESH","db_id":"D002544"}]},{"id":"10152","type":"Chemical","text":["phenylpropanolamine"],"offsets":[[47,66]],"normalized":[{"db_name":"MESH","db_id":"D010665"}]},{"id":"10153","type":"Chemical","text":["Phenylpropanolamine"],"offsets":[[68,87]],"normalized":[{"db_name":"MESH","db_id":"D010665"}]},{"id":"10154","type":"Chemical","text":["PPA"],"offsets":[[89,92]],"normalized":[{"db_name":"MESH","db_id":"D010665"}]},{"id":"10155","type":"Chemical","text":["amphetamine"],"offsets":[[155,166]],"normalized":[{"db_name":"MESH","db_id":"D000661"}]},{"id":"10156","type":"Disease","text":["seizures"],"offsets":[[309,317]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"10157","type":"Disease","text":["intracerebral hemorrhage"],"offsets":[[319,343]],"normalized":[{"db_name":"MESH","db_id":"D002543"}]},{"id":"10158","type":"Disease","text":["neuropsychiatric symptoms"],"offsets":[[345,370]],"normalized":[{"db_name":"MESH","db_id":"D001523"}]},{"id":"10159","type":"Disease","text":["cerebral infarction"],"offsets":[[391,410]],"normalized":[{"db_name":"MESH","db_id":"D002544"}]},{"id":"10160","type":"Disease","text":["cerebral infarction"],"offsets":[[463,482]],"normalized":[{"db_name":"MESH","db_id":"D002544"}]},{"id":"10161","type":"Chemical","text":["PPA"],"offsets":[[518,521]],"normalized":[{"db_name":"MESH","db_id":"D010665"}]}],"events":[],"coreferences":[],"relations":[{"id":"10162","type":"CID","arg1_id":"10152","arg2_id":"10158","normalized":[]},{"id":"10163","type":"CID","arg1_id":"10153","arg2_id":"10158","normalized":[]},{"id":"10164","type":"CID","arg1_id":"10154","arg2_id":"10158","normalized":[]},{"id":"10165","type":"CID","arg1_id":"10161","arg2_id":"10158","normalized":[]},{"id":"10166","type":"CID","arg1_id":"10152","arg2_id":"10156","normalized":[]},{"id":"10167","type":"CID","arg1_id":"10153","arg2_id":"10156","normalized":[]},{"id":"10168","type":"CID","arg1_id":"10154","arg2_id":"10156","normalized":[]},{"id":"10169","type":"CID","arg1_id":"10161","arg2_id":"10156","normalized":[]},{"id":"10170","type":"CID","arg1_id":"10152","arg2_id":"10151","normalized":[]},{"id":"10171","type":"CID","arg1_id":"10152","arg2_id":"10159","normalized":[]},{"id":"10172","type":"CID","arg1_id":"10152","arg2_id":"10160","normalized":[]},{"id":"10173","type":"CID","arg1_id":"10153","arg2_id":"10151","normalized":[]},{"id":"10174","type":"CID","arg1_id":"10153","arg2_id":"10159","normalized":[]},{"id":"10175","type":"CID","arg1_id":"10153","arg2_id":"10160","normalized":[]},{"id":"10176","type":"CID","arg1_id":"10154","arg2_id":"10151","normalized":[]},{"id":"10177","type":"CID","arg1_id":"10154","arg2_id":"10159","normalized":[]},{"id":"10178","type":"CID","arg1_id":"10154","arg2_id":"10160","normalized":[]},{"id":"10179","type":"CID","arg1_id":"10161","arg2_id":"10151","normalized":[]},{"id":"10180","type":"CID","arg1_id":"10161","arg2_id":"10159","normalized":[]},{"id":"10181","type":"CID","arg1_id":"10161","arg2_id":"10160","normalized":[]},{"id":"10182","type":"CID","arg1_id":"10152","arg2_id":"10157","normalized":[]},{"id":"10183","type":"CID","arg1_id":"10153","arg2_id":"10157","normalized":[]},{"id":"10184","type":"CID","arg1_id":"10154","arg2_id":"10157","normalized":[]},{"id":"10185","type":"CID","arg1_id":"10161","arg2_id":"10157","normalized":[]}]}
{"id":"10186","document_id":"4812392","passages":[{"id":"10187","type":"title","text":["Treatment of psoriasis with azathioprine."],"offsets":[[0,41]]},{"id":"10188","type":"abstract","text":["Azathioprine treatment benefited 19 (66%) out of 29 patients suffering from severe psoriasis. Haematological complications were not troublesome and results of biochemical liver function tests remained normal. Minimal cholestasis was seen in two cases and portal fibrosis of a reversible degree in eight. Liver biopsies should be undertaken at regular intervals if azathioprine therapy is continued so that structural liver damage may be detected at an early and reversible stage."],"offsets":[[42,521]]}],"entities":[{"id":"10189","type":"Disease","text":["psoriasis"],"offsets":[[13,22]],"normalized":[{"db_name":"MESH","db_id":"D011565"}]},{"id":"10190","type":"Chemical","text":["azathioprine"],"offsets":[[28,40]],"normalized":[{"db_name":"MESH","db_id":"D001379"}]},{"id":"10191","type":"Chemical","text":["Azathioprine"],"offsets":[[42,54]],"normalized":[{"db_name":"MESH","db_id":"D001379"}]},{"id":"10192","type":"Disease","text":["psoriasis"],"offsets":[[125,134]],"normalized":[{"db_name":"MESH","db_id":"D011565"}]},{"id":"10193","type":"Disease","text":["cholestasis"],"offsets":[[259,270]],"normalized":[{"db_name":"MESH","db_id":"D002779"}]},{"id":"10194","type":"Disease","text":["fibrosis"],"offsets":[[304,312]],"normalized":[{"db_name":"MESH","db_id":"D005355"}]},{"id":"10195","type":"Chemical","text":["azathioprine"],"offsets":[[406,418]],"normalized":[{"db_name":"MESH","db_id":"D001379"}]},{"id":"10196","type":"Disease","text":["liver damage"],"offsets":[[459,471]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]}],"events":[],"coreferences":[],"relations":[{"id":"10197","type":"CID","arg1_id":"10190","arg2_id":"10194","normalized":[]},{"id":"10198","type":"CID","arg1_id":"10191","arg2_id":"10194","normalized":[]},{"id":"10199","type":"CID","arg1_id":"10195","arg2_id":"10194","normalized":[]},{"id":"10200","type":"CID","arg1_id":"10190","arg2_id":"10193","normalized":[]},{"id":"10201","type":"CID","arg1_id":"10191","arg2_id":"10193","normalized":[]},{"id":"10202","type":"CID","arg1_id":"10195","arg2_id":"10193","normalized":[]}]}
{"id":"10203","document_id":"6518066","passages":[{"id":"10204","type":"title","text":["Maternal lithium and neonatal Ebstein's anomaly: evaluation with cross-sectional echocardiography."],"offsets":[[0,98]]},{"id":"10205","type":"abstract","text":["Cross-sectional echocardiography was used to evaluate two neonates whose mothers ingested lithium during pregnancy. In one infant, Ebstein's anomaly of the tricuspid valve was identified. In the other infant cross-sectional echocardiography provided reassurance that the infant did not have Ebstein's anomaly. Cross-sectional echocardiographic screening of newborns exposed to lithium during gestation can provide highly accurate, noninvasive assessment of the presence or absence of lithium-induced cardiac malformations."],"offsets":[[99,621]]}],"entities":[{"id":"10206","type":"Chemical","text":["lithium"],"offsets":[[9,16]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"10207","type":"Disease","text":["Ebstein's anomaly"],"offsets":[[30,47]],"normalized":[{"db_name":"MESH","db_id":"D004437"}]},{"id":"10208","type":"Chemical","text":["lithium"],"offsets":[[189,196]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"10209","type":"Disease","text":["Ebstein's anomaly"],"offsets":[[230,247]],"normalized":[{"db_name":"MESH","db_id":"D004437"}]},{"id":"10210","type":"Disease","text":["Ebstein's anomaly"],"offsets":[[390,407]],"normalized":[{"db_name":"MESH","db_id":"D004437"}]},{"id":"10211","type":"Chemical","text":["lithium"],"offsets":[[476,483]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"10212","type":"Chemical","text":["lithium"],"offsets":[[583,590]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"10213","type":"Disease","text":["cardiac malformations"],"offsets":[[599,620]],"normalized":[{"db_name":"MESH","db_id":"D006331"}]}],"events":[],"coreferences":[],"relations":[{"id":"10214","type":"CID","arg1_id":"10206","arg2_id":"10207","normalized":[]},{"id":"10215","type":"CID","arg1_id":"10206","arg2_id":"10209","normalized":[]},{"id":"10216","type":"CID","arg1_id":"10206","arg2_id":"10210","normalized":[]},{"id":"10217","type":"CID","arg1_id":"10208","arg2_id":"10207","normalized":[]},{"id":"10218","type":"CID","arg1_id":"10208","arg2_id":"10209","normalized":[]},{"id":"10219","type":"CID","arg1_id":"10208","arg2_id":"10210","normalized":[]},{"id":"10220","type":"CID","arg1_id":"10211","arg2_id":"10207","normalized":[]},{"id":"10221","type":"CID","arg1_id":"10211","arg2_id":"10209","normalized":[]},{"id":"10222","type":"CID","arg1_id":"10211","arg2_id":"10210","normalized":[]},{"id":"10223","type":"CID","arg1_id":"10212","arg2_id":"10207","normalized":[]},{"id":"10224","type":"CID","arg1_id":"10212","arg2_id":"10209","normalized":[]},{"id":"10225","type":"CID","arg1_id":"10212","arg2_id":"10210","normalized":[]}]}
{"id":"10226","document_id":"6534871","passages":[{"id":"10227","type":"title","text":["Effects of training on the extent of experimental myocardial infarction in aging rats."],"offsets":[[0,86]]},{"id":"10228","type":"abstract","text":["The effects of exercise on the severity of isoproterenol-induced myocardial infarction were studied in female albino rats of 20,40,60 and 80 weeks of age. The rats were trained to swim for a specific duration and for a particular period. The occurrence of infarcts were confirmed by histological methods. Elevations in the serum GOT and GPT were maximum in the sedentary-isoproterenols and minimum in the exercise-controls. These changes in the serum transaminases were associated with corresponding depletions in the cardiac GOT and GPT. However, age was seen to interfere with the responses exhibited by the young and old rats. Studies dealing with myocardial infarction are more informative when dealt with age."],"offsets":[[87,801]]}],"entities":[{"id":"10229","type":"Disease","text":["myocardial infarction"],"offsets":[[50,71]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"10230","type":"Chemical","text":["isoproterenol"],"offsets":[[130,143]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"10231","type":"Disease","text":["myocardial infarction"],"offsets":[[152,173]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"10232","type":"Disease","text":["infarcts"],"offsets":[[343,351]],"normalized":[{"db_name":"MESH","db_id":"D007238"}]},{"id":"10233","type":"Chemical","text":["isoproterenols"],"offsets":[[458,472]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"10234","type":"Disease","text":["myocardial infarction"],"offsets":[[738,759]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]}],"events":[],"coreferences":[],"relations":[{"id":"10235","type":"CID","arg1_id":"10230","arg2_id":"10229","normalized":[]},{"id":"10236","type":"CID","arg1_id":"10230","arg2_id":"10231","normalized":[]},{"id":"10237","type":"CID","arg1_id":"10230","arg2_id":"10234","normalized":[]},{"id":"10238","type":"CID","arg1_id":"10233","arg2_id":"10229","normalized":[]},{"id":"10239","type":"CID","arg1_id":"10233","arg2_id":"10231","normalized":[]},{"id":"10240","type":"CID","arg1_id":"10233","arg2_id":"10234","normalized":[]}]}
{"id":"10241","document_id":"6538499","passages":[{"id":"10242","type":"title","text":["Effect of polyethylene glycol 400 on adriamycin toxicity in mice."],"offsets":[[0,65]]},{"id":"10243","type":"abstract","text":["The effect of a widely used organic solvent, polyethylene glycol 400 (PEG 400), on the toxic action of an acute or chronic treatment with adriamycin (ADR) was evaluated in mice. PEG 400 impressively decreased both acute high-dose and chronic low-dose-ADR-associated lethality. Light microscopic analysis showed a significant protection against ADR-induced cardiac morphological alterations. Such treatment did not diminish the ADR antitumor activity in L1210 leukemia and in Ehrlich ascites tumor."],"offsets":[[66,563]]}],"entities":[{"id":"10244","type":"Chemical","text":["polyethylene glycol 400"],"offsets":[[10,33]],"normalized":[{"db_name":"MESH","db_id":"D011092"}]},{"id":"10245","type":"Chemical","text":["adriamycin"],"offsets":[[37,47]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"10246","type":"Disease","text":["toxicity"],"offsets":[[48,56]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"10247","type":"Chemical","text":["polyethylene glycol 400"],"offsets":[[111,134]],"normalized":[{"db_name":"MESH","db_id":"D011092"}]},{"id":"10248","type":"Chemical","text":["PEG 400"],"offsets":[[136,143]],"normalized":[{"db_name":"MESH","db_id":"D011092"}]},{"id":"10249","type":"Chemical","text":["adriamycin"],"offsets":[[204,214]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"10250","type":"Chemical","text":["ADR"],"offsets":[[216,219]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"10251","type":"Chemical","text":["PEG 400"],"offsets":[[244,251]],"normalized":[{"db_name":"MESH","db_id":"D011092"}]},{"id":"10252","type":"Chemical","text":["ADR"],"offsets":[[317,320]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"10253","type":"Chemical","text":["ADR"],"offsets":[[410,413]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"10254","type":"Disease","text":["cardiac morphological alterations"],"offsets":[[422,455]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"10255","type":"Chemical","text":["ADR"],"offsets":[[493,496]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"10256","type":"Disease","text":["L1210 leukemia"],"offsets":[[519,533]],"normalized":[{"db_name":"MESH","db_id":"D007939"}]},{"id":"10257","type":"Disease","text":["Ehrlich ascites tumor"],"offsets":[[541,562]],"normalized":[{"db_name":"MESH","db_id":"D002286"}]}],"events":[],"coreferences":[],"relations":[{"id":"10258","type":"CID","arg1_id":"10245","arg2_id":"10254","normalized":[]},{"id":"10259","type":"CID","arg1_id":"10249","arg2_id":"10254","normalized":[]},{"id":"10260","type":"CID","arg1_id":"10250","arg2_id":"10254","normalized":[]},{"id":"10261","type":"CID","arg1_id":"10252","arg2_id":"10254","normalized":[]},{"id":"10262","type":"CID","arg1_id":"10253","arg2_id":"10254","normalized":[]},{"id":"10263","type":"CID","arg1_id":"10255","arg2_id":"10254","normalized":[]}]}
{"id":"10264","document_id":"6747681","passages":[{"id":"10265","type":"title","text":["Intra-arterial BCNU chemotherapy for treatment of malignant gliomas of the central nervous system."],"offsets":[[0,98]]},{"id":"10266","type":"abstract","text":["Because of the rapid systemic clearance of BCNU (1,3-bis-(2-chloroethyl)-1-nitrosourea), intra-arterial administration should provide a substantial advantage over intravenous administration for the treatment of malignant gliomas. Thirty-six patients were treated with BCNU every 6 to 8 weeks, either by transfemoral catheterization of the internal carotid or vertebral artery or through a fully implantable intracarotid drug delivery system, beginning with a dose of 200 mg\/sq m body surface area. Twelve patients with Grade III or IV astrocytomas were treated after partial resection of the tumor without prior radiation therapy. After two to seven cycles of chemotherapy, nine patients showed a decrease in tumor size and surrounding edema on contrast-enhanced computerized tomography scans. In the nine responders, median duration of chemotherapy response from the time of operation was 25 weeks (range 12 to more than 91 weeks). The median duration of survival in the 12 patients was 54 weeks (range 21 to more than 156 weeks), with an 18-month survival rate of 42%. Twenty-four patients with recurrent Grade I to IV astrocytomas, whose resection and irradiation therapy had failed, received two to eight courses of intra-arterial BCNU therapy. Seventeen of these had a response or were stable for a median of 20 weeks (range 6 to more than 66 weeks). The catheterization procedure is safe, with no immediate complication in 111 infusions of BCNU. A delayed complication in nine patients has been unilateral loss of vision secondary to a retinal vasculitis. The frequency of visual loss decreased after the concentration of the ethanol diluent was lowered."],"offsets":[[99,1759]]}],"entities":[{"id":"10267","type":"Chemical","text":["BCNU"],"offsets":[[15,19]],"normalized":[{"db_name":"MESH","db_id":"D002330"}]},{"id":"10268","type":"Disease","text":["malignant gliomas"],"offsets":[[50,67]],"normalized":[{"db_name":"MESH","db_id":"D005910"}]},{"id":"10269","type":"Chemical","text":["BCNU"],"offsets":[[142,146]],"normalized":[{"db_name":"MESH","db_id":"D002330"}]},{"id":"10270","type":"Chemical","text":["1,3-bis-(2-chloroethyl)-1-nitrosourea"],"offsets":[[148,185]],"normalized":[{"db_name":"MESH","db_id":"D002330"}]},{"id":"10271","type":"Disease","text":["malignant gliomas"],"offsets":[[310,327]],"normalized":[{"db_name":"MESH","db_id":"D005910"}]},{"id":"10272","type":"Chemical","text":["BCNU"],"offsets":[[367,371]],"normalized":[{"db_name":"MESH","db_id":"D002330"}]},{"id":"10273","type":"Disease","text":["astrocytomas"],"offsets":[[634,646]],"normalized":[{"db_name":"MESH","db_id":"D001254"}]},{"id":"10274","type":"Disease","text":["tumor"],"offsets":[[691,696]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"10275","type":"Disease","text":["tumor"],"offsets":[[808,813]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"10276","type":"Disease","text":["edema"],"offsets":[[835,840]],"normalized":[{"db_name":"MESH","db_id":"D004487"}]},{"id":"10277","type":"Disease","text":["astrocytomas"],"offsets":[[1220,1232]],"normalized":[{"db_name":"MESH","db_id":"D001254"}]},{"id":"10278","type":"Chemical","text":["BCNU"],"offsets":[[1334,1338]],"normalized":[{"db_name":"MESH","db_id":"D002330"}]},{"id":"10279","type":"Chemical","text":["BCNU"],"offsets":[[1545,1549]],"normalized":[{"db_name":"MESH","db_id":"D002330"}]},{"id":"10280","type":"Disease","text":["loss of vision"],"offsets":[[1611,1625]],"normalized":[{"db_name":"MESH","db_id":"D014786"}]},{"id":"10281","type":"Disease","text":["retinal vasculitis"],"offsets":[[1641,1659]],"normalized":[{"db_name":"MESH","db_id":"D031300"}]},{"id":"10282","type":"Disease","text":["visual loss"],"offsets":[[1678,1689]],"normalized":[{"db_name":"MESH","db_id":"D014786"}]},{"id":"10283","type":"Chemical","text":["ethanol"],"offsets":[[1731,1738]],"normalized":[{"db_name":"MESH","db_id":"D000431"}]}],"events":[],"coreferences":[],"relations":[{"id":"10284","type":"CID","arg1_id":"10267","arg2_id":"10281","normalized":[]},{"id":"10285","type":"CID","arg1_id":"10269","arg2_id":"10281","normalized":[]},{"id":"10286","type":"CID","arg1_id":"10270","arg2_id":"10281","normalized":[]},{"id":"10287","type":"CID","arg1_id":"10272","arg2_id":"10281","normalized":[]},{"id":"10288","type":"CID","arg1_id":"10278","arg2_id":"10281","normalized":[]},{"id":"10289","type":"CID","arg1_id":"10279","arg2_id":"10281","normalized":[]}]}
{"id":"10290","document_id":"6861444","passages":[{"id":"10291","type":"title","text":["Blood pressure response to chronic low-dose intrarenal noradrenaline infusion in conscious rats."],"offsets":[[0,96]]},{"id":"10292","type":"abstract","text":["Sodium chloride solution (0.9%) or noradrenaline in doses of 4, 12 and 36 micrograms h-1 kg-1 was infused for five consecutive days, either intrarenally (by a new technique) or intravenously into rats with one kidney removed. Intrarenal infusion of noradrenaline caused hypertension at doses which did not do so when infused intravenously. Intrarenal compared with intravenous infusion of noradrenaline caused higher plasma noradrenaline concentrations and a shift of the plasma noradrenaline concentration-blood pressure effect curve towards lower plasma noradrenaline levels. These results suggest that hypertension after chronic intrarenal noradrenaline infusion is produced by relatively higher levels of circulating noradrenaline and by triggering of an additional intrarenal pressor mechanism."],"offsets":[[97,896]]}],"entities":[{"id":"10293","type":"Chemical","text":["noradrenaline"],"offsets":[[55,68]],"normalized":[{"db_name":"MESH","db_id":"D009638"}]},{"id":"10294","type":"Chemical","text":["Sodium chloride"],"offsets":[[97,112]],"normalized":[{"db_name":"MESH","db_id":"D012965"}]},{"id":"10295","type":"Chemical","text":["noradrenaline"],"offsets":[[132,145]],"normalized":[{"db_name":"MESH","db_id":"D009638"}]},{"id":"10296","type":"Chemical","text":["noradrenaline"],"offsets":[[346,359]],"normalized":[{"db_name":"MESH","db_id":"D009638"}]},{"id":"10297","type":"Disease","text":["hypertension"],"offsets":[[367,379]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"10298","type":"Chemical","text":["noradrenaline"],"offsets":[[486,499]],"normalized":[{"db_name":"MESH","db_id":"D009638"}]},{"id":"10299","type":"Chemical","text":["noradrenaline"],"offsets":[[521,534]],"normalized":[{"db_name":"MESH","db_id":"D009638"}]},{"id":"10300","type":"Chemical","text":["noradrenaline"],"offsets":[[576,589]],"normalized":[{"db_name":"MESH","db_id":"D009638"}]},{"id":"10301","type":"Chemical","text":["noradrenaline"],"offsets":[[653,666]],"normalized":[{"db_name":"MESH","db_id":"D009638"}]},{"id":"10302","type":"Disease","text":["hypertension"],"offsets":[[702,714]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"10303","type":"Chemical","text":["noradrenaline"],"offsets":[[740,753]],"normalized":[{"db_name":"MESH","db_id":"D009638"}]},{"id":"10304","type":"Chemical","text":["noradrenaline"],"offsets":[[818,831]],"normalized":[{"db_name":"MESH","db_id":"D009638"}]}],"events":[],"coreferences":[],"relations":[{"id":"10305","type":"CID","arg1_id":"10293","arg2_id":"10297","normalized":[]},{"id":"10306","type":"CID","arg1_id":"10293","arg2_id":"10302","normalized":[]},{"id":"10307","type":"CID","arg1_id":"10295","arg2_id":"10297","normalized":[]},{"id":"10308","type":"CID","arg1_id":"10295","arg2_id":"10302","normalized":[]},{"id":"10309","type":"CID","arg1_id":"10296","arg2_id":"10297","normalized":[]},{"id":"10310","type":"CID","arg1_id":"10296","arg2_id":"10302","normalized":[]},{"id":"10311","type":"CID","arg1_id":"10298","arg2_id":"10297","normalized":[]},{"id":"10312","type":"CID","arg1_id":"10298","arg2_id":"10302","normalized":[]},{"id":"10313","type":"CID","arg1_id":"10299","arg2_id":"10297","normalized":[]},{"id":"10314","type":"CID","arg1_id":"10299","arg2_id":"10302","normalized":[]},{"id":"10315","type":"CID","arg1_id":"10300","arg2_id":"10297","normalized":[]},{"id":"10316","type":"CID","arg1_id":"10300","arg2_id":"10302","normalized":[]},{"id":"10317","type":"CID","arg1_id":"10301","arg2_id":"10297","normalized":[]},{"id":"10318","type":"CID","arg1_id":"10301","arg2_id":"10302","normalized":[]},{"id":"10319","type":"CID","arg1_id":"10303","arg2_id":"10297","normalized":[]},{"id":"10320","type":"CID","arg1_id":"10303","arg2_id":"10302","normalized":[]},{"id":"10321","type":"CID","arg1_id":"10304","arg2_id":"10297","normalized":[]},{"id":"10322","type":"CID","arg1_id":"10304","arg2_id":"10302","normalized":[]}]}
{"id":"10323","document_id":"7053303","passages":[{"id":"10324","type":"title","text":["Age and renal clearance of cimetidine."],"offsets":[[0,38]]},{"id":"10325","type":"abstract","text":["In 35 patients (ages 20 to 86 yr) receiving cimetidine therapeutically two serum samples and all urine formed in the interim were collected for analysis of cimetidine by high-pressure liquid chromatography and for creatinine. Cimetidine clearance decreased with age. The extrapolated 6-hr serum concentration of cimetidine per unit dose, after intravenous cimetidine, increased with age of the patients. The ratio of cimetidine clearance to creatinine clearance (Rc) averaged 4.8 +\/- 2.0, indicating net tubular secretion for cimetidine. Rc seemed to be independent of age and decreased with increasing serum concentration of cimetidine, suggesting that secretion of cimetidine is a saturable process. There was only one case of dementia possibly due to cimetidine (with a drug level of 1.9 microgram\/ml 6 hr after a dose) in a group of 13 patients without liver or kidney disease who had cimetidine levels above 1.25 microgram\/ml. Thus, high cimetidine levels alone do not always induce dementia."],"offsets":[[39,1036]]}],"entities":[{"id":"10326","type":"Chemical","text":["cimetidine"],"offsets":[[27,37]],"normalized":[{"db_name":"MESH","db_id":"D002927"}]},{"id":"10327","type":"Chemical","text":["cimetidine"],"offsets":[[83,93]],"normalized":[{"db_name":"MESH","db_id":"D002927"}]},{"id":"10328","type":"Chemical","text":["cimetidine"],"offsets":[[195,205]],"normalized":[{"db_name":"MESH","db_id":"D002927"}]},{"id":"10329","type":"Chemical","text":["creatinine"],"offsets":[[253,263]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"10330","type":"Chemical","text":["Cimetidine"],"offsets":[[265,275]],"normalized":[{"db_name":"MESH","db_id":"D002927"}]},{"id":"10331","type":"Chemical","text":["cimetidine"],"offsets":[[351,361]],"normalized":[{"db_name":"MESH","db_id":"D002927"}]},{"id":"10332","type":"Chemical","text":["cimetidine"],"offsets":[[395,405]],"normalized":[{"db_name":"MESH","db_id":"D002927"}]},{"id":"10333","type":"Chemical","text":["cimetidine"],"offsets":[[456,466]],"normalized":[{"db_name":"MESH","db_id":"D002927"}]},{"id":"10334","type":"Chemical","text":["creatinine"],"offsets":[[480,490]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"10335","type":"Chemical","text":["cimetidine"],"offsets":[[565,575]],"normalized":[{"db_name":"MESH","db_id":"D002927"}]},{"id":"10336","type":"Chemical","text":["cimetidine"],"offsets":[[665,675]],"normalized":[{"db_name":"MESH","db_id":"D002927"}]},{"id":"10337","type":"Chemical","text":["cimetidine"],"offsets":[[706,716]],"normalized":[{"db_name":"MESH","db_id":"D002927"}]},{"id":"10338","type":"Disease","text":["dementia"],"offsets":[[768,776]],"normalized":[{"db_name":"MESH","db_id":"D003704"}]},{"id":"10339","type":"Chemical","text":["cimetidine"],"offsets":[[793,803]],"normalized":[{"db_name":"MESH","db_id":"D002927"}]},{"id":"10340","type":"Disease","text":["liver or kidney disease"],"offsets":[[896,919]],"normalized":[{"db_name":"MESH","db_id":"D008107"},{"db_name":"MESH","db_id":"D007674"}]},{"id":"10341","type":"Disease","text":["liver","disease"],"offsets":[[896,901],[912,919]],"normalized":[{"db_name":"MESH","db_id":"D008107"}]},{"id":"10342","type":"Disease","text":["kidney disease"],"offsets":[[905,919]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"10343","type":"Chemical","text":["cimetidine"],"offsets":[[928,938]],"normalized":[{"db_name":"MESH","db_id":"D002927"}]},{"id":"10344","type":"Chemical","text":["cimetidine"],"offsets":[[982,992]],"normalized":[{"db_name":"MESH","db_id":"D002927"}]},{"id":"10345","type":"Disease","text":["dementia"],"offsets":[[1027,1035]],"normalized":[{"db_name":"MESH","db_id":"D003704"}]}],"events":[],"coreferences":[],"relations":[{"id":"10346","type":"CID","arg1_id":"10326","arg2_id":"10338","normalized":[]},{"id":"10347","type":"CID","arg1_id":"10326","arg2_id":"10345","normalized":[]},{"id":"10348","type":"CID","arg1_id":"10327","arg2_id":"10338","normalized":[]},{"id":"10349","type":"CID","arg1_id":"10327","arg2_id":"10345","normalized":[]},{"id":"10350","type":"CID","arg1_id":"10328","arg2_id":"10338","normalized":[]},{"id":"10351","type":"CID","arg1_id":"10328","arg2_id":"10345","normalized":[]},{"id":"10352","type":"CID","arg1_id":"10330","arg2_id":"10338","normalized":[]},{"id":"10353","type":"CID","arg1_id":"10330","arg2_id":"10345","normalized":[]},{"id":"10354","type":"CID","arg1_id":"10331","arg2_id":"10338","normalized":[]},{"id":"10355","type":"CID","arg1_id":"10331","arg2_id":"10345","normalized":[]},{"id":"10356","type":"CID","arg1_id":"10332","arg2_id":"10338","normalized":[]},{"id":"10357","type":"CID","arg1_id":"10332","arg2_id":"10345","normalized":[]},{"id":"10358","type":"CID","arg1_id":"10333","arg2_id":"10338","normalized":[]},{"id":"10359","type":"CID","arg1_id":"10333","arg2_id":"10345","normalized":[]},{"id":"10360","type":"CID","arg1_id":"10335","arg2_id":"10338","normalized":[]},{"id":"10361","type":"CID","arg1_id":"10335","arg2_id":"10345","normalized":[]},{"id":"10362","type":"CID","arg1_id":"10336","arg2_id":"10338","normalized":[]},{"id":"10363","type":"CID","arg1_id":"10336","arg2_id":"10345","normalized":[]},{"id":"10364","type":"CID","arg1_id":"10337","arg2_id":"10338","normalized":[]},{"id":"10365","type":"CID","arg1_id":"10337","arg2_id":"10345","normalized":[]},{"id":"10366","type":"CID","arg1_id":"10339","arg2_id":"10338","normalized":[]},{"id":"10367","type":"CID","arg1_id":"10339","arg2_id":"10345","normalized":[]},{"id":"10368","type":"CID","arg1_id":"10343","arg2_id":"10338","normalized":[]},{"id":"10369","type":"CID","arg1_id":"10343","arg2_id":"10345","normalized":[]},{"id":"10370","type":"CID","arg1_id":"10344","arg2_id":"10338","normalized":[]},{"id":"10371","type":"CID","arg1_id":"10344","arg2_id":"10345","normalized":[]}]}
{"id":"10372","document_id":"7088431","passages":[{"id":"10373","type":"title","text":["Development of clear cell adenocarcinoma in DES-exposed offspring under observation."],"offsets":[[0,84]]},{"id":"10374","type":"abstract","text":["Two cases of clear cell adenocarcinoma of the vagina detected at follow-up in young women exposed in utero to diethylstilbestrol are reported. One patient, aged 23, had been followed for 2 years before carcinoma was diagnosed; the second patient, aged 22, had been seen on a regular basis for 5 years, 8 months. In both instances, suspicion of the presence of carcinoma was aroused by the palpation of a small nodule in the vaginal fornix. Hysterosalpingography was performed on both patients and, in 1 instance, an abnormal x-ray film was reflected by the gross appearance of the uterine cavity found in the surgical specimen."],"offsets":[[85,712]]}],"entities":[{"id":"10375","type":"Disease","text":["clear cell adenocarcinoma"],"offsets":[[15,40]],"normalized":[{"db_name":"MESH","db_id":"D018262"}]},{"id":"10376","type":"Chemical","text":["DES"],"offsets":[[44,47]],"normalized":[{"db_name":"MESH","db_id":"D004054"}]},{"id":"10377","type":"Disease","text":["clear cell adenocarcinoma of the vagina"],"offsets":[[98,137]],"normalized":[{"db_name":"MESH","db_id":"D018262"},{"db_name":"MESH","db_id":"D014625"}]},{"id":"10378","type":"Disease","text":["clear cell adenocarcinoma"],"offsets":[[98,123]],"normalized":[{"db_name":"MESH","db_id":"D018262"}]},{"id":"10379","type":"Disease","text":["adenocarcinoma of the vagina"],"offsets":[[109,137]],"normalized":[{"db_name":"MESH","db_id":"D014625"}]},{"id":"10380","type":"Chemical","text":["diethylstilbestrol"],"offsets":[[195,213]],"normalized":[{"db_name":"MESH","db_id":"D004054"}]},{"id":"10381","type":"Disease","text":["carcinoma"],"offsets":[[287,296]],"normalized":[{"db_name":"MESH","db_id":"D002277"}]},{"id":"10382","type":"Disease","text":["carcinoma"],"offsets":[[445,454]],"normalized":[{"db_name":"MESH","db_id":"D002277"}]}],"events":[],"coreferences":[],"relations":[{"id":"10383","type":"CID","arg1_id":"10376","arg2_id":"10377","normalized":[]},{"id":"10384","type":"CID","arg1_id":"10376","arg2_id":"10379","normalized":[]},{"id":"10385","type":"CID","arg1_id":"10380","arg2_id":"10377","normalized":[]},{"id":"10386","type":"CID","arg1_id":"10380","arg2_id":"10379","normalized":[]},{"id":"10387","type":"CID","arg1_id":"10376","arg2_id":"10375","normalized":[]},{"id":"10388","type":"CID","arg1_id":"10376","arg2_id":"10377","normalized":[]},{"id":"10389","type":"CID","arg1_id":"10376","arg2_id":"10378","normalized":[]},{"id":"10390","type":"CID","arg1_id":"10380","arg2_id":"10375","normalized":[]},{"id":"10391","type":"CID","arg1_id":"10380","arg2_id":"10377","normalized":[]},{"id":"10392","type":"CID","arg1_id":"10380","arg2_id":"10378","normalized":[]}]}
{"id":"10393","document_id":"7248170","passages":[{"id":"10394","type":"title","text":["Phenobarbitone-induced enlargement of the liver in the rat: its relationship to carbon tetrachloride-induced cirrhosis."],"offsets":[[0,119]]},{"id":"10395","type":"abstract","text":["The yield of severe cirrhosis of the liver (defined as a shrunken finely nodular liver with micronodular histology, ascites greater than 30 ml, plasma albumin less than 2.2 g\/dl, splenomegaly 2-3 times normal, and testicular atrophy approximately half normal weight) after 12 doses of carbon tetrachloride given intragastrically in the phenobarbitone-primed rat was increased from 25% to 56% by giving the initial \"calibrating\" dose of carbon tetrachloride at the peak of the phenobarbitone-induced enlargement of the liver. At this point it was assumed that the cytochrome P450\/CCl4 toxic state was both maximal and stable. The optimal rat size to begin phenobarbitone was determined as 100 g, and this size as a group had a mean maximum relative liver weight increase 47% greater than normal rats of the same body weight. The optimal time for the initial dose of carbon tetrachloride was after 14 days on phenobarbitone."],"offsets":[[120,1042]]}],"entities":[{"id":"10396","type":"Chemical","text":["Phenobarbitone"],"offsets":[[0,14]],"normalized":[{"db_name":"MESH","db_id":"D010634"}]},{"id":"10397","type":"Disease","text":["enlargement of the liver"],"offsets":[[23,47]],"normalized":[{"db_name":"MESH","db_id":"D006529"}]},{"id":"10398","type":"Chemical","text":["carbon tetrachloride"],"offsets":[[80,100]],"normalized":[{"db_name":"MESH","db_id":"D002251"}]},{"id":"10399","type":"Disease","text":["cirrhosis"],"offsets":[[109,118]],"normalized":[{"db_name":"MESH","db_id":"D005355"}]},{"id":"10400","type":"Disease","text":["cirrhosis of the liver"],"offsets":[[140,162]],"normalized":[{"db_name":"MESH","db_id":"D008103"}]},{"id":"10401","type":"Disease","text":["ascites"],"offsets":[[236,243]],"normalized":[{"db_name":"MESH","db_id":"D001201"}]},{"id":"10402","type":"Disease","text":["splenomegaly"],"offsets":[[299,311]],"normalized":[{"db_name":"MESH","db_id":"D013163"}]},{"id":"10403","type":"Disease","text":["atrophy"],"offsets":[[345,352]],"normalized":[{"db_name":"MESH","db_id":"D001284"}]},{"id":"10404","type":"Chemical","text":["carbon tetrachloride"],"offsets":[[405,425]],"normalized":[{"db_name":"MESH","db_id":"D002251"}]},{"id":"10405","type":"Chemical","text":["phenobarbitone"],"offsets":[[456,470]],"normalized":[{"db_name":"MESH","db_id":"D010634"}]},{"id":"10406","type":"Chemical","text":["carbon tetrachloride"],"offsets":[[556,576]],"normalized":[{"db_name":"MESH","db_id":"D002251"}]},{"id":"10407","type":"Chemical","text":["phenobarbitone"],"offsets":[[596,610]],"normalized":[{"db_name":"MESH","db_id":"D010634"}]},{"id":"10408","type":"Disease","text":["enlargement of the liver"],"offsets":[[619,643]],"normalized":[{"db_name":"MESH","db_id":"D006529"}]},{"id":"10409","type":"Chemical","text":["CCl4"],"offsets":[[699,703]],"normalized":[{"db_name":"MESH","db_id":"D002251"}]},{"id":"10410","type":"Chemical","text":["phenobarbitone"],"offsets":[[775,789]],"normalized":[{"db_name":"MESH","db_id":"D010634"}]},{"id":"10411","type":"Chemical","text":["carbon tetrachloride"],"offsets":[[985,1005]],"normalized":[{"db_name":"MESH","db_id":"D002251"}]},{"id":"10412","type":"Chemical","text":["phenobarbitone"],"offsets":[[1027,1041]],"normalized":[{"db_name":"MESH","db_id":"D010634"}]}],"events":[],"coreferences":[],"relations":[{"id":"10413","type":"CID","arg1_id":"10396","arg2_id":"10400","normalized":[]},{"id":"10414","type":"CID","arg1_id":"10405","arg2_id":"10400","normalized":[]},{"id":"10415","type":"CID","arg1_id":"10407","arg2_id":"10400","normalized":[]},{"id":"10416","type":"CID","arg1_id":"10410","arg2_id":"10400","normalized":[]},{"id":"10417","type":"CID","arg1_id":"10412","arg2_id":"10400","normalized":[]},{"id":"10418","type":"CID","arg1_id":"10398","arg2_id":"10400","normalized":[]},{"id":"10419","type":"CID","arg1_id":"10404","arg2_id":"10400","normalized":[]},{"id":"10420","type":"CID","arg1_id":"10406","arg2_id":"10400","normalized":[]},{"id":"10421","type":"CID","arg1_id":"10409","arg2_id":"10400","normalized":[]},{"id":"10422","type":"CID","arg1_id":"10411","arg2_id":"10400","normalized":[]},{"id":"10423","type":"CID","arg1_id":"10396","arg2_id":"10397","normalized":[]},{"id":"10424","type":"CID","arg1_id":"10396","arg2_id":"10408","normalized":[]},{"id":"10425","type":"CID","arg1_id":"10405","arg2_id":"10397","normalized":[]},{"id":"10426","type":"CID","arg1_id":"10405","arg2_id":"10408","normalized":[]},{"id":"10427","type":"CID","arg1_id":"10407","arg2_id":"10397","normalized":[]},{"id":"10428","type":"CID","arg1_id":"10407","arg2_id":"10408","normalized":[]},{"id":"10429","type":"CID","arg1_id":"10410","arg2_id":"10397","normalized":[]},{"id":"10430","type":"CID","arg1_id":"10410","arg2_id":"10408","normalized":[]},{"id":"10431","type":"CID","arg1_id":"10412","arg2_id":"10397","normalized":[]},{"id":"10432","type":"CID","arg1_id":"10412","arg2_id":"10408","normalized":[]}]}
{"id":"10433","document_id":"7453952","passages":[{"id":"10434","type":"title","text":["Attenuation of the lithium-induced diabetes-insipidus-like syndrome by amiloride in rats."],"offsets":[[0,89]]},{"id":"10435","type":"abstract","text":["The effect of amiloride on lithium-induced polydipsia and polyuria and on the lithium concentration in the plasma, brain, kidney, thyroid and red blood cells was investigated in rats, chronically treated with LiCl. Amiloride reduced the drinking and urine volume of rats in an acute (6 or 12 h) and a subacute (3 days) experiment. 6 h after the administration of amiloride, a reduction was observed in the lithium content of the renal medulla but not in the other organs studied. At 12 h, all the tissues showed a slight increase in lithium levels. After 3 days of combined treatment, a marked elevation in plasma and tissue lithium levels accompanied a reduction in water intake. In all the experiments, the attenuation of the lithium-induced diabetes-insipidus-like syndrome by amiloride was accompanied by a reduction of the ratio between the lithium concentration in the renal medulla and its levels in the blood and an elevation in the plasma potassium level. It is concluded that acute amiloride administration to lithium-treated patients suffering from polydipsia and polyuria might relieve these patients but prolonged amiloride supplementation would result in elevated lithium levels and might be hazardous."],"offsets":[[90,1306]]}],"entities":[{"id":"10436","type":"Chemical","text":["lithium"],"offsets":[[19,26]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"10437","type":"Disease","text":["diabetes-insipidus-like syndrome"],"offsets":[[35,67]],"normalized":[{"db_name":"MESH","db_id":"D003919"}]},{"id":"10438","type":"Chemical","text":["amiloride"],"offsets":[[71,80]],"normalized":[{"db_name":"MESH","db_id":"D000584"}]},{"id":"10439","type":"Chemical","text":["amiloride"],"offsets":[[104,113]],"normalized":[{"db_name":"MESH","db_id":"D000584"}]},{"id":"10440","type":"Chemical","text":["lithium"],"offsets":[[117,124]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"10441","type":"Disease","text":["polydipsia"],"offsets":[[133,143]],"normalized":[{"db_name":"MESH","db_id":"D059606"}]},{"id":"10442","type":"Disease","text":["polyuria"],"offsets":[[148,156]],"normalized":[{"db_name":"MESH","db_id":"D011141"}]},{"id":"10443","type":"Chemical","text":["lithium"],"offsets":[[168,175]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"10444","type":"Chemical","text":["LiCl"],"offsets":[[299,303]],"normalized":[{"db_name":"MESH","db_id":"D018021"}]},{"id":"10445","type":"Chemical","text":["Amiloride"],"offsets":[[305,314]],"normalized":[{"db_name":"MESH","db_id":"D000584"}]},{"id":"10446","type":"Chemical","text":["amiloride"],"offsets":[[453,462]],"normalized":[{"db_name":"MESH","db_id":"D000584"}]},{"id":"10447","type":"Chemical","text":["lithium"],"offsets":[[496,503]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"10448","type":"Chemical","text":["lithium"],"offsets":[[623,630]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"10449","type":"Chemical","text":["lithium"],"offsets":[[715,722]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"10450","type":"Chemical","text":["lithium"],"offsets":[[818,825]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"10451","type":"Disease","text":["diabetes-insipidus-like syndrome"],"offsets":[[834,866]],"normalized":[{"db_name":"MESH","db_id":"D003919"}]},{"id":"10452","type":"Chemical","text":["amiloride"],"offsets":[[870,879]],"normalized":[{"db_name":"MESH","db_id":"D000584"}]},{"id":"10453","type":"Chemical","text":["lithium"],"offsets":[[936,943]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"10454","type":"Chemical","text":["potassium"],"offsets":[[1038,1047]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"10455","type":"Chemical","text":["amiloride"],"offsets":[[1082,1091]],"normalized":[{"db_name":"MESH","db_id":"D000584"}]},{"id":"10456","type":"Chemical","text":["lithium"],"offsets":[[1110,1117]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"10457","type":"Disease","text":["polydipsia"],"offsets":[[1150,1160]],"normalized":[{"db_name":"MESH","db_id":"D059606"}]},{"id":"10458","type":"Disease","text":["polyuria"],"offsets":[[1165,1173]],"normalized":[{"db_name":"MESH","db_id":"D011141"}]},{"id":"10459","type":"Chemical","text":["amiloride"],"offsets":[[1217,1226]],"normalized":[{"db_name":"MESH","db_id":"D000584"}]},{"id":"10460","type":"Chemical","text":["lithium"],"offsets":[[1268,1275]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]}],"events":[],"coreferences":[],"relations":[{"id":"10461","type":"CID","arg1_id":"10436","arg2_id":"10437","normalized":[]},{"id":"10462","type":"CID","arg1_id":"10436","arg2_id":"10451","normalized":[]},{"id":"10463","type":"CID","arg1_id":"10440","arg2_id":"10437","normalized":[]},{"id":"10464","type":"CID","arg1_id":"10440","arg2_id":"10451","normalized":[]},{"id":"10465","type":"CID","arg1_id":"10443","arg2_id":"10437","normalized":[]},{"id":"10466","type":"CID","arg1_id":"10443","arg2_id":"10451","normalized":[]},{"id":"10467","type":"CID","arg1_id":"10447","arg2_id":"10437","normalized":[]},{"id":"10468","type":"CID","arg1_id":"10447","arg2_id":"10451","normalized":[]},{"id":"10469","type":"CID","arg1_id":"10448","arg2_id":"10437","normalized":[]},{"id":"10470","type":"CID","arg1_id":"10448","arg2_id":"10451","normalized":[]},{"id":"10471","type":"CID","arg1_id":"10449","arg2_id":"10437","normalized":[]},{"id":"10472","type":"CID","arg1_id":"10449","arg2_id":"10451","normalized":[]},{"id":"10473","type":"CID","arg1_id":"10450","arg2_id":"10437","normalized":[]},{"id":"10474","type":"CID","arg1_id":"10450","arg2_id":"10451","normalized":[]},{"id":"10475","type":"CID","arg1_id":"10453","arg2_id":"10437","normalized":[]},{"id":"10476","type":"CID","arg1_id":"10453","arg2_id":"10451","normalized":[]},{"id":"10477","type":"CID","arg1_id":"10456","arg2_id":"10437","normalized":[]},{"id":"10478","type":"CID","arg1_id":"10456","arg2_id":"10451","normalized":[]},{"id":"10479","type":"CID","arg1_id":"10460","arg2_id":"10437","normalized":[]},{"id":"10480","type":"CID","arg1_id":"10460","arg2_id":"10451","normalized":[]}]}
{"id":"10481","document_id":"7802851","passages":[{"id":"10482","type":"title","text":["Safety and side-effects of alprazolam. Controlled study in agoraphobia with panic disorder."],"offsets":[[0,91]]},{"id":"10483","type":"abstract","text":["BACKGROUND: The widespread use of benzodiazepines has led to increasing recognition of their unwanted effects. The efficacy of alprazolam and placebo in panic disorder with agoraphobia, and the side-effect and adverse effect profiles of both drug groups were measured. METHOD: In London and Toronto 154 patients who met DSM-III criteria for panic disorder with agoraphobia were randomised to alprazolam or placebo. Subjects in each drug group also received either exposure or relaxation. Treatment was from weeks 0 to 8 and was then tapered from weeks 8 to 16. RESULTS: Mean alprazolam dose was 5 mg daily. Compared with placebo subjects, alprazolam patients developed more adverse reactions (21% v. 0%) of depression, enuresis, disinhibition and aggression; and more side-effects, particularly sedation, irritability, impaired memory, weight loss and ataxia. Side-effects tended to diminish during treatment but remained significant at week 8. Despite this, the drop-out rate was low. CONCLUSIONS: Alprazolam caused side-effects and adverse effects during treatment but many patients were willing to accept these."],"offsets":[[92,1206]]}],"entities":[{"id":"10484","type":"Chemical","text":["alprazolam"],"offsets":[[27,37]],"normalized":[{"db_name":"MESH","db_id":"D000525"}]},{"id":"10485","type":"Disease","text":["agoraphobia"],"offsets":[[59,70]],"normalized":[{"db_name":"MESH","db_id":"D000379"}]},{"id":"10486","type":"Disease","text":["panic disorder"],"offsets":[[76,90]],"normalized":[{"db_name":"MESH","db_id":"D016584"}]},{"id":"10487","type":"Chemical","text":["benzodiazepines"],"offsets":[[126,141]],"normalized":[{"db_name":"MESH","db_id":"D001569"}]},{"id":"10488","type":"Chemical","text":["alprazolam"],"offsets":[[219,229]],"normalized":[{"db_name":"MESH","db_id":"D000525"}]},{"id":"10489","type":"Disease","text":["panic disorder"],"offsets":[[245,259]],"normalized":[{"db_name":"MESH","db_id":"D016584"}]},{"id":"10490","type":"Disease","text":["agoraphobia"],"offsets":[[265,276]],"normalized":[{"db_name":"MESH","db_id":"D000379"}]},{"id":"10491","type":"Disease","text":["panic 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{"id":"10534","document_id":"8319760","passages":[{"id":"10535","type":"title","text":["Dup 753 prevents the development of puromycin aminonucleoside-induced nephrosis."],"offsets":[[0,80]]},{"id":"10536","type":"abstract","text":["The appearance of nephrotic syndromes such as proteinuria, hypoalbuminemia, hypercholesterolemia and increase in blood nitrogen urea, induced in rats by injection of puromycin aminonucleoside was markedly inhibited by oral administration of Dup 753 (losartan), a novel angiotensin II receptor antagonist, at a dose of 1 or 2 mg\/kg per day. The results suggest a possible involvement of the renin-angiotensin system in the development of puromycin aminonucleoside-induced nephrosis."],"offsets":[[81,562]]}],"entities":[{"id":"10537","type":"Chemical","text":["Dup 753"],"offsets":[[0,7]],"normalized":[{"db_name":"MESH","db_id":"D019808"}]},{"id":"10538","type":"Chemical","text":["puromycin aminonucleoside"],"offsets":[[36,61]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"10539","type":"Disease","text":["nephrosis"],"offsets":[[70,79]],"normalized":[{"db_name":"MESH","db_id":"D009401"}]},{"id":"10540","type":"Disease","text":["nephrotic syndromes"],"offsets":[[99,118]],"normalized":[{"db_name":"MESH","db_id":"D009404"}]},{"id":"10541","type":"Disease","text":["proteinuria"],"offsets":[[127,138]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]},{"id":"10542","type":"Disease","text":["hypoalbuminemia"],"offsets":[[140,155]],"normalized":[{"db_name":"MESH","db_id":"D034141"}]},{"id":"10543","type":"Disease","text":["hypercholesterolemia"],"offsets":[[157,177]],"normalized":[{"db_name":"MESH","db_id":"D006937"}]},{"id":"10544","type":"Chemical","text":["blood nitrogen urea"],"offsets":[[194,213]],"normalized":[{"db_name":"MESH","db_id":"D001806"}]},{"id":"10545","type":"Chemical","text":["puromycin aminonucleoside"],"offsets":[[247,272]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"10546","type":"Chemical","text":["Dup 753"],"offsets":[[322,329]],"normalized":[{"db_name":"MESH","db_id":"D019808"}]},{"id":"10547","type":"Chemical","text":["losartan"],"offsets":[[331,339]],"normalized":[{"db_name":"MESH","db_id":"D019808"}]},{"id":"10548","type":"Chemical","text":["angiotensin II"],"offsets":[[350,364]],"normalized":[{"db_name":"MESH","db_id":"D000804"}]},{"id":"10549","type":"Chemical","text":["angiotensin"],"offsets":[[477,488]],"normalized":[{"db_name":"MESH","db_id":"D000809"}]},{"id":"10550","type":"Chemical","text":["puromycin aminonucleoside"],"offsets":[[518,543]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"10551","type":"Disease","text":["nephrosis"],"offsets":[[552,561]],"normalized":[{"db_name":"MESH","db_id":"D009401"}]}],"events":[],"coreferences":[],"relations":[{"id":"10552","type":"CID","arg1_id":"10538","arg2_id":"10543","normalized":[]},{"id":"10553","type":"CID","arg1_id":"10545","arg2_id":"10543","normalized":[]},{"id":"10554","type":"CID","arg1_id":"10550","arg2_id":"10543","normalized":[]},{"id":"10555","type":"CID","arg1_id":"10538","arg2_id":"10541","normalized":[]},{"id":"10556","type":"CID","arg1_id":"10545","arg2_id":"10541","normalized":[]},{"id":"10557","type":"CID","arg1_id":"10550","arg2_id":"10541","normalized":[]},{"id":"10558","type":"CID","arg1_id":"10538","arg2_id":"10540","normalized":[]},{"id":"10559","type":"CID","arg1_id":"10545","arg2_id":"10540","normalized":[]},{"id":"10560","type":"CID","arg1_id":"10550","arg2_id":"10540","normalized":[]},{"id":"10561","type":"CID","arg1_id":"10538","arg2_id":"10542","normalized":[]},{"id":"10562","type":"CID","arg1_id":"10545","arg2_id":"10542","normalized":[]},{"id":"10563","type":"CID","arg1_id":"10550","arg2_id":"10542","normalized":[]}]}
{"id":"10564","document_id":"8386779","passages":[{"id":"10565","type":"title","text":["Sodium bicarbonate alleviates penile pain induced by intracavernous injections for erectile dysfunction."],"offsets":[[0,104]]},{"id":"10566","type":"abstract","text":["In an attempt to determine whether penile pain associated with intracorporeal injections could be due to the acidity of the medication, we performed a randomized study comparing the incidence of penile pain following intracorporeal injections with or without the addition of sodium bicarbonate to the intracorporeal medications. A total of 38 consecutive patients who presented to our clinic with impotence received 0.2 ml. of a combination of 3 drugs: 6 mg. papaverine, 100 micrograms. phentolamine and 10 micrograms. prostaglandin E1 with (pH 7.05) or without (pH 4.17) the addition of sodium bicarbonate (0.03 mEq.). Of the 19 patients without sodium bicarbonate added to the medication 11 (58%) complained of penile pain due to the medication, while only 1 of the 19 men (5%) who received sodium bicarbonate complained of penile pain. From these data we conclude that the penile pain following intracorporeal injections is most likely due to the acidity of the medication, which can be overcome by elevating the pH to a neutral level."],"offsets":[[105,1143]]}],"entities":[{"id":"10567","type":"Chemical","text":["Sodium bicarbonate"],"offsets":[[0,18]],"normalized":[{"db_name":"MESH","db_id":"D017693"}]},{"id":"10568","type":"Disease","text":["penile pain"],"offsets":[[30,41]],"normalized":[{"db_name":"MESH","db_id":"D004414"}]},{"id":"10569","type":"Disease","text":["erectile dysfunction"],"offsets":[[83,103]],"normalized":[{"db_name":"MESH","db_id":"D007172"}]},{"id":"10570","type":"Disease","text":["penile pain"],"offsets":[[140,151]],"normalized":[{"db_name":"MESH","db_id":"D004414"}]},{"id":"10571","type":"Disease","text":["penile pain"],"offsets":[[300,311]],"normalized":[{"db_name":"MESH","db_id":"D004414"}]},{"id":"10572","type":"Chemical","text":["sodium bicarbonate"],"offsets":[[380,398]],"normalized":[{"db_name":"MESH","db_id":"D017693"}]},{"id":"10573","type":"Disease","text":["impotence"],"offsets":[[502,511]],"normalized":[{"db_name":"MESH","db_id":"D007172"}]},{"id":"10574","type":"Chemical","text":["papaverine"],"offsets":[[564,574]],"normalized":[{"db_name":"MESH","db_id":"D010208"}]},{"id":"10575","type":"Chemical","text":["phentolamine"],"offsets":[[592,604]],"normalized":[{"db_name":"MESH","db_id":"D010646"}]},{"id":"10576","type":"Chemical","text":["prostaglandin E1"],"offsets":[[624,640]],"normalized":[{"db_name":"MESH","db_id":"D000527"}]},{"id":"10577","type":"Chemical","text":["sodium bicarbonate"],"offsets":[[693,711]],"normalized":[{"db_name":"MESH","db_id":"D017693"}]},{"id":"10578","type":"Chemical","text":["sodium bicarbonate"],"offsets":[[752,770]],"normalized":[{"db_name":"MESH","db_id":"D017693"}]},{"id":"10579","type":"Disease","text":["penile pain"],"offsets":[[818,829]],"normalized":[{"db_name":"MESH","db_id":"D004414"}]},{"id":"10580","type":"Chemical","text":["sodium bicarbonate"],"offsets":[[898,916]],"normalized":[{"db_name":"MESH","db_id":"D017693"}]},{"id":"10581","type":"Disease","text":["penile pain"],"offsets":[[931,942]],"normalized":[{"db_name":"MESH","db_id":"D004414"}]},{"id":"10582","type":"Disease","text":["penile pain"],"offsets":[[981,992]],"normalized":[{"db_name":"MESH","db_id":"D004414"}]}],"events":[],"coreferences":[],"relations":[{"id":"10583","type":"CID","arg1_id":"10575","arg2_id":"10568","normalized":[]},{"id":"10584","type":"CID","arg1_id":"10575","arg2_id":"10570","normalized":[]},{"id":"10585","type":"CID","arg1_id":"10575","arg2_id":"10571","normalized":[]},{"id":"10586","type":"CID","arg1_id":"10575","arg2_id":"10579","normalized":[]},{"id":"10587","type":"CID","arg1_id":"10575","arg2_id":"10581","normalized":[]},{"id":"10588","type":"CID","arg1_id":"10575","arg2_id":"10582","normalized":[]},{"id":"10589","type":"CID","arg1_id":"10576","arg2_id":"10568","normalized":[]},{"id":"10590","type":"CID","arg1_id":"10576","arg2_id":"10570","normalized":[]},{"id":"10591","type":"CID","arg1_id":"10576","arg2_id":"10571","normalized":[]},{"id":"10592","type":"CID","arg1_id":"10576","arg2_id":"10579","normalized":[]},{"id":"10593","type":"CID","arg1_id":"10576","arg2_id":"10581","normalized":[]},{"id":"10594","type":"CID","arg1_id":"10576","arg2_id":"10582","normalized":[]}]}
{"id":"10595","document_id":"8421099","passages":[{"id":"10596","type":"title","text":["Prospective study of the long-term effects of somatostatin analog (octreotide) on gallbladder function and gallstone formation in Chinese acromegalic patients."],"offsets":[[0,159]]},{"id":"10597","type":"abstract","text":["This article reports the changes in gallbladder function examined by ultrasonography in 20 Chinese patients with active acromegaly treated with sc injection of the somatostatin analog octreotide in dosages of 300-1500 micrograms\/day for a mean of 24.2 +\/- 13.9 months. During treatment with octreotide, 17 patients developed sludge, 10 had gallstones, and 1 developed acute cholecystitis requiring surgery. In all of 7 patients examined acutely, gallbladder contractility was inhibited after a single 100-micrograms injection. In 8 patients followed for 24 weeks, gallbladder contractility remained depressed throughout therapy. After withdrawal of octreotide in 10 patients without gallstones, 8 patients assessed had return of normal gallbladder contractility within 1 month. In 8 of the remaining 10 patients who developed gallstones during treatment, gallbladder contractility normalized in 5 patients (3 of whom has disappearance of their stones within 3 weeks), and remained depressed in 3 (2 of whom had stones present at 6 months). Our results suggest that the suppression of gallbladder contractility is the cause of the successive formation of bile sludge, gallstones, and cholecystitis during octreotide therapy in Chinese acromegalic patients. It is therefore very important to follow the changes of gallbladder function during long-term octreotide therapy of acromegalic patients."],"offsets":[[160,1553]]}],"entities":[{"id":"10598","type":"Chemical","text":["octreotide"],"offsets":[[67,77]],"normalized":[{"db_name":"MESH","db_id":"D015282"}]},{"id":"10599","type":"Disease","text":["gallstone"],"offsets":[[107,116]],"normalized":[{"db_name":"MESH","db_id":"D042882"}]},{"id":"10600","type":"Disease","text":["acromegalic"],"offsets":[[138,149]],"normalized":[{"db_name":"MESH","db_id":"D000172"}]},{"id":"10601","type":"Disease","text":["acromegaly"],"offsets":[[280,290]],"normalized":[{"db_name":"MESH","db_id":"D000172"}]},{"id":"10602","type":"Chemical","text":["octreotide"],"offsets":[[344,354]],"normalized":[{"db_name":"MESH","db_id":"D015282"}]},{"id":"10603","type":"Chemical","text":["octreotide"],"offsets":[[451,461]],"normalized":[{"db_name":"MESH","db_id":"D015282"}]},{"id":"10604","type":"Disease","text":["gallstones"],"offsets":[[500,510]],"normalized":[{"db_name":"MESH","db_id":"D042882"}]},{"id":"10605","type":"Disease","text":["acute cholecystitis"],"offsets":[[528,547]],"normalized":[{"db_name":"MESH","db_id":"D041881"}]},{"id":"10606","type":"Disease","text":["depressed"],"offsets":[[759,768]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"10607","type":"Chemical","text":["octreotide"],"offsets":[[809,819]],"normalized":[{"db_name":"MESH","db_id":"D015282"}]},{"id":"10608","type":"Disease","text":["gallstones"],"offsets":[[843,853]],"normalized":[{"db_name":"MESH","db_id":"D042882"}]},{"id":"10609","type":"Disease","text":["gallstones"],"offsets":[[986,996]],"normalized":[{"db_name":"MESH","db_id":"D042882"}]},{"id":"10610","type":"Disease","text":["depressed"],"offsets":[[1141,1150]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"10611","type":"Disease","text":["gallstones"],"offsets":[[1327,1337]],"normalized":[{"db_name":"MESH","db_id":"D042882"}]},{"id":"10612","type":"Disease","text":["cholecystitis"],"offsets":[[1343,1356]],"normalized":[{"db_name":"MESH","db_id":"D002764"}]},{"id":"10613","type":"Chemical","text":["octreotide"],"offsets":[[1364,1374]],"normalized":[{"db_name":"MESH","db_id":"D015282"}]},{"id":"10614","type":"Disease","text":["acromegalic"],"offsets":[[1394,1405]],"normalized":[{"db_name":"MESH","db_id":"D000172"}]},{"id":"10615","type":"Chemical","text":["octreotide"],"offsets":[[1510,1520]],"normalized":[{"db_name":"MESH","db_id":"D015282"}]},{"id":"10616","type":"Disease","text":["acromegalic"],"offsets":[[1532,1543]],"normalized":[{"db_name":"MESH","db_id":"D000172"}]}],"events":[],"coreferences":[],"relations":[{"id":"10617","type":"CID","arg1_id":"10598","arg2_id":"10605","normalized":[]},{"id":"10618","type":"CID","arg1_id":"10602","arg2_id":"10605","normalized":[]},{"id":"10619","type":"CID","arg1_id":"10603","arg2_id":"10605","normalized":[]},{"id":"10620","type":"CID","arg1_id":"10607","arg2_id":"10605","normalized":[]},{"id":"10621","type":"CID","arg1_id":"10613","arg2_id":"10605","normalized":[]},{"id":"10622","type":"CID","arg1_id":"10615","arg2_id":"10605","normalized":[]},{"id":"10623","type":"CID","arg1_id":"10598","arg2_id":"10599","normalized":[]},{"id":"10624","type":"CID","arg1_id":"10598","arg2_id":"10604","normalized":[]},{"id":"10625","type":"CID","arg1_id":"10598","arg2_id":"10608","normalized":[]},{"id":"10626","type":"CID","arg1_id":"10598","arg2_id":"10609","normalized":[]},{"id":"10627","type":"CID","arg1_id":"10598","arg2_id":"10611","normalized":[]},{"id":"10628","type":"CID","arg1_id":"10602","arg2_id":"10599","normalized":[]},{"id":"10629","type":"CID","arg1_id":"10602","arg2_id":"10604","normalized":[]},{"id":"10630","type":"CID","arg1_id":"10602","arg2_id":"10608","normalized":[]},{"id":"10631","type":"CID","arg1_id":"10602","arg2_id":"10609","normalized":[]},{"id":"10632","type":"CID","arg1_id":"10602","arg2_id":"10611","normalized":[]},{"id":"10633","type":"CID","arg1_id":"10603","arg2_id":"10599","normalized":[]},{"id":"10634","type":"CID","arg1_id":"10603","arg2_id":"10604","normalized":[]},{"id":"10635","type":"CID","arg1_id":"10603","arg2_id":"10608","normalized":[]},{"id":"10636","type":"CID","arg1_id":"10603","arg2_id":"10609","normalized":[]},{"id":"10637","type":"CID","arg1_id":"10603","arg2_id":"10611","normalized":[]},{"id":"10638","type":"CID","arg1_id":"10607","arg2_id":"10599","normalized":[]},{"id":"10639","type":"CID","arg1_id":"10607","arg2_id":"10604","normalized":[]},{"id":"10640","type":"CID","arg1_id":"10607","arg2_id":"10608","normalized":[]},{"id":"10641","type":"CID","arg1_id":"10607","arg2_id":"10609","normalized":[]},{"id":"10642","type":"CID","arg1_id":"10607","arg2_id":"10611","normalized":[]},{"id":"10643","type":"CID","arg1_id":"10613","arg2_id":"10599","normalized":[]},{"id":"10644","type":"CID","arg1_id":"10613","arg2_id":"10604","normalized":[]},{"id":"10645","type":"CID","arg1_id":"10613","arg2_id":"10608","normalized":[]},{"id":"10646","type":"CID","arg1_id":"10613","arg2_id":"10609","normalized":[]},{"id":"10647","type":"CID","arg1_id":"10613","arg2_id":"10611","normalized":[]},{"id":"10648","type":"CID","arg1_id":"10615","arg2_id":"10599","normalized":[]},{"id":"10649","type":"CID","arg1_id":"10615","arg2_id":"10604","normalized":[]},{"id":"10650","type":"CID","arg1_id":"10615","arg2_id":"10608","normalized":[]},{"id":"10651","type":"CID","arg1_id":"10615","arg2_id":"10609","normalized":[]},{"id":"10652","type":"CID","arg1_id":"10615","arg2_id":"10611","normalized":[]}]}
{"id":"10653","document_id":"8649546","passages":[{"id":"10654","type":"title","text":["Improvement of levodopa-induced dyskinesia by propranolol in Parkinson's disease."],"offsets":[[0,81]]},{"id":"10655","type":"abstract","text":["Seven patients suffering from Parkinson's disease (PD) with severely disabling dyskinesia received low-dose propranolol as an adjunct to the currently used medical treatment. There was a significant 40% improvement in the dyskinesia score without increase of parkinsonian motor disability. Ballistic and choreic dyskinesia were markedly ameliorated, whereas dystonia was not. This study suggests that administration of low doses of beta-blockers may improve levodopa-induced ballistic and choreic dyskinesia in PD."],"offsets":[[82,596]]}],"entities":[{"id":"10656","type":"Chemical","text":["levodopa"],"offsets":[[15,23]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"10657","type":"Disease","text":["dyskinesia"],"offsets":[[32,42]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"10658","type":"Chemical","text":["propranolol"],"offsets":[[46,57]],"normalized":[{"db_name":"MESH","db_id":"D011433"}]},{"id":"10659","type":"Disease","text":["Parkinson's disease"],"offsets":[[61,80]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"10660","type":"Disease","text":["Parkinson's disease"],"offsets":[[112,131]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"10661","type":"Disease","text":["PD"],"offsets":[[133,135]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"10662","type":"Disease","text":["dyskinesia"],"offsets":[[161,171]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"10663","type":"Chemical","text":["propranolol"],"offsets":[[190,201]],"normalized":[{"db_name":"MESH","db_id":"D011433"}]},{"id":"10664","type":"Disease","text":["dyskinesia"],"offsets":[[304,314]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"10665","type":"Disease","text":["parkinsonian"],"offsets":[[341,353]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"10666","type":"Disease","text":["motor disability"],"offsets":[[354,370]],"normalized":[{"db_name":"MESH","db_id":"D009069"}]},{"id":"10667","type":"Disease","text":["dyskinesia"],"offsets":[[394,404]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"10668","type":"Disease","text":["dystonia"],"offsets":[[440,448]],"normalized":[{"db_name":"MESH","db_id":"D004421"}]},{"id":"10669","type":"Chemical","text":["levodopa"],"offsets":[[540,548]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"10670","type":"Disease","text":["dyskinesia"],"offsets":[[579,589]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"10671","type":"Disease","text":["PD"],"offsets":[[593,595]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]}],"events":[],"coreferences":[],"relations":[{"id":"10672","type":"CID","arg1_id":"10656","arg2_id":"10657","normalized":[]},{"id":"10673","type":"CID","arg1_id":"10656","arg2_id":"10662","normalized":[]},{"id":"10674","type":"CID","arg1_id":"10656","arg2_id":"10664","normalized":[]},{"id":"10675","type":"CID","arg1_id":"10656","arg2_id":"10667","normalized":[]},{"id":"10676","type":"CID","arg1_id":"10656","arg2_id":"10670","normalized":[]},{"id":"10677","type":"CID","arg1_id":"10669","arg2_id":"10657","normalized":[]},{"id":"10678","type":"CID","arg1_id":"10669","arg2_id":"10662","normalized":[]},{"id":"10679","type":"CID","arg1_id":"10669","arg2_id":"10664","normalized":[]},{"id":"10680","type":"CID","arg1_id":"10669","arg2_id":"10667","normalized":[]},{"id":"10681","type":"CID","arg1_id":"10669","arg2_id":"10670","normalized":[]}]}
{"id":"10682","document_id":"8919272","passages":[{"id":"10683","type":"title","text":["Morphological features of encephalopathy after chronic administration of the antiepileptic drug valproate to rats. A transmission electron microscopic study of capillaries in the cerebellar cortex."],"offsets":[[0,197]]},{"id":"10684","type":"abstract","text":["Long-term intragastric application of the antiepileptic drug sodium valproate (Vupral \"Polfa\") at the effective dose of 200 mg\/kg b. w. once daily to rats for 1, 3, 6, 9 and 12 months revealed neurological disorders indicating cerebellum damage (\"valproate encephalopathy\"). The first ultrastructural changes in structural elements of the blood-brain-barrier (BBB) in the cerebellar cortex were detectable after 3 months of the experiment. They became more severe in the later months of the experiment, and were most severe after 12 months, located mainly in the molecular layer of the cerebellar cortex. Lesions of the capillary included necrosis of endothelial cells. Organelles of these cells, in particular the mitochondria (increased number and size, distinct degeneration of their matrix and cristae) and Golgi apparatus were altered. Reduced size of capillary lumen and occlusion were caused by swollen endothelial cells which had luminal protrusions and swollen microvilli. Pressure on the vessel wall was produced by enlarged perivascular astrocytic processes. Fragments of necrotic endothelial cells were in the vascular lumens and in these there was loosening and breaking of tight cellular junctions. Damage to the vascular basement lamina was also observed. Damage to the capillary was accompanied by marked damage to neuroglial cells, mainly to perivascular processes of astrocytes. The proliferation of astrocytes (Bergmann's in particular) and occasionally of oligodendrocytes was found. Alterations in the structural elements of the BBB coexisted with marked lesions of neurons of the cerebellum (Purkinje cells are earliest). In electron micrographs both luminal and antiluminal sides of the BBB of the cerebellar cortex had similar lesions. The possible influence of the hepatic damage, mainly hyperammonemia, upon the development of valproate encephalopathy is discussed."],"offsets":[[198,2089]]}],"entities":[{"id":"10685","type":"Disease","text":["encephalopathy"],"offsets":[[26,40]],"normalized":[{"db_name":"MESH","db_id":"D001927"}]},{"id":"10686","type":"Chemical","text":["valproate"],"offsets":[[96,105]],"normalized":[{"db_name":"MESH","db_id":"D014635"}]},{"id":"10687","type":"Chemical","text":["sodium valproate"],"offsets":[[259,275]],"normalized":[{"db_name":"MESH","db_id":"D014635"}]},{"id":"10688","type":"Disease","text":["neurological disorders"],"offsets":[[391,413]],"normalized":[{"db_name":"MESH","db_id":"D009422"}]},{"id":"10689","type":"Disease","text":["cerebellum damage"],"offsets":[[425,442]],"normalized":[{"db_name":"MESH","db_id":"D002526"}]},{"id":"10690","type":"Chemical","text":["valproate"],"offsets":[[445,454]],"normalized":[{"db_name":"MESH","db_id":"D014635"}]},{"id":"10691","type":"Disease","text":["encephalopathy"],"offsets":[[455,469]],"normalized":[{"db_name":"MESH","db_id":"D001927"}]},{"id":"10692","type":"Disease","text":["necrosis"],"offsets":[[837,845]],"normalized":[{"db_name":"MESH","db_id":"D009336"}]},{"id":"10693","type":"Chemical","text":["luminal"],"offsets":[[1136,1143]],"normalized":[{"db_name":"MESH","db_id":"D010634"}]},{"id":"10694","type":"Disease","text":["necrotic"],"offsets":[[1281,1289]],"normalized":[{"db_name":"MESH","db_id":"D009336"}]},{"id":"10695","type":"Chemical","text":["luminal"],"offsets":[[1871,1878]],"normalized":[{"db_name":"MESH","db_id":"D010634"}]},{"id":"10696","type":"Disease","text":["hepatic damage"],"offsets":[[1988,2002]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"10697","type":"Disease","text":["hyperammonemia"],"offsets":[[2011,2025]],"normalized":[{"db_name":"MESH","db_id":"D022124"}]},{"id":"10698","type":"Chemical","text":["valproate"],"offsets":[[2051,2060]],"normalized":[{"db_name":"MESH","db_id":"D014635"}]},{"id":"10699","type":"Disease","text":["encephalopathy"],"offsets":[[2061,2075]],"normalized":[{"db_name":"MESH","db_id":"D001927"}]}],"events":[],"coreferences":[],"relations":[{"id":"10700","type":"CID","arg1_id":"10686","arg2_id":"10685","normalized":[]},{"id":"10701","type":"CID","arg1_id":"10686","arg2_id":"10691","normalized":[]},{"id":"10702","type":"CID","arg1_id":"10686","arg2_id":"10699","normalized":[]},{"id":"10703","type":"CID","arg1_id":"10687","arg2_id":"10685","normalized":[]},{"id":"10704","type":"CID","arg1_id":"10687","arg2_id":"10691","normalized":[]},{"id":"10705","type":"CID","arg1_id":"10687","arg2_id":"10699","normalized":[]},{"id":"10706","type":"CID","arg1_id":"10690","arg2_id":"10685","normalized":[]},{"id":"10707","type":"CID","arg1_id":"10690","arg2_id":"10691","normalized":[]},{"id":"10708","type":"CID","arg1_id":"10690","arg2_id":"10699","normalized":[]},{"id":"10709","type":"CID","arg1_id":"10698","arg2_id":"10685","normalized":[]},{"id":"10710","type":"CID","arg1_id":"10698","arg2_id":"10691","normalized":[]},{"id":"10711","type":"CID","arg1_id":"10698","arg2_id":"10699","normalized":[]}]}
{"id":"10712","document_id":"9199746","passages":[{"id":"10713","type":"title","text":["Macula toxicity after intravitreal amikacin."],"offsets":[[0,44]]},{"id":"10714","type":"abstract","text":["BACKGROUND: Although intravitreal aminoglycosides have substantially improved visual prognosis in endophthalmitis, macular infarction may impair full visual recovery. METHODS: We present a case of presumed amikacin retinal toxicity following treatment with amikacin and vancomycin for alpha-haemolytic streptococcal endophthalmitis. RESULTS: Endophthalmitis resolved with improvement in visual acuity to 6\/24 at three months. Fundus fluorescein angiography confirmed macular capillary closure and telangiectasis. CONCLUSIONS: Currently accepted intravitreal antibiotic regimens may cause retinal toxicity and macular ischaemia. Treatment strategies aimed at avoiding retinal toxicity are discussed."],"offsets":[[45,743]]}],"entities":[{"id":"10715","type":"Disease","text":["toxicity"],"offsets":[[7,15]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"10716","type":"Chemical","text":["amikacin"],"offsets":[[35,43]],"normalized":[{"db_name":"MESH","db_id":"D000583"}]},{"id":"10717","type":"Chemical","text":["aminoglycosides"],"offsets":[[79,94]],"normalized":[{"db_name":"MESH","db_id":"D000617"}]},{"id":"10718","type":"Disease","text":["endophthalmitis"],"offsets":[[143,158]],"normalized":[{"db_name":"MESH","db_id":"D009877"}]},{"id":"10719","type":"Disease","text":["infarction"],"offsets":[[168,178]],"normalized":[{"db_name":"MESH","db_id":"D007238"}]},{"id":"10720","type":"Chemical","text":["amikacin"],"offsets":[[251,259]],"normalized":[{"db_name":"MESH","db_id":"D000583"}]},{"id":"10721","type":"Disease","text":["retinal toxicity"],"offsets":[[260,276]],"normalized":[{"db_name":"MESH","db_id":"D012164"}]},{"id":"10722","type":"Chemical","text":["amikacin"],"offsets":[[302,310]],"normalized":[{"db_name":"MESH","db_id":"D000583"}]},{"id":"10723","type":"Chemical","text":["vancomycin"],"offsets":[[315,325]],"normalized":[{"db_name":"MESH","db_id":"D014640"}]},{"id":"10724","type":"Disease","text":["streptococcal endophthalmitis"],"offsets":[[347,376]],"normalized":[{"db_name":"MESH","db_id":"D013290"}]},{"id":"10725","type":"Disease","text":["Endophthalmitis"],"offsets":[[387,402]],"normalized":[{"db_name":"MESH","db_id":"D009877"}]},{"id":"10726","type":"Chemical","text":["fluorescein"],"offsets":[[478,489]],"normalized":[{"db_name":"MESH","db_id":"D019793"}]},{"id":"10727","type":"Disease","text":["telangiectasis"],"offsets":[[542,556]],"normalized":[{"db_name":"MESH","db_id":"D013684"}]},{"id":"10728","type":"Disease","text":["retinal toxicity"],"offsets":[[633,649]],"normalized":[{"db_name":"MESH","db_id":"D012164"}]},{"id":"10729","type":"Disease","text":["ischaemia"],"offsets":[[662,671]],"normalized":[{"db_name":"MESH","db_id":"D007511"}]},{"id":"10730","type":"Disease","text":["retinal toxicity"],"offsets":[[712,728]],"normalized":[{"db_name":"MESH","db_id":"D012164"}]}],"events":[],"coreferences":[],"relations":[{"id":"10731","type":"CID","arg1_id":"10716","arg2_id":"10729","normalized":[]},{"id":"10732","type":"CID","arg1_id":"10720","arg2_id":"10729","normalized":[]},{"id":"10733","type":"CID","arg1_id":"10722","arg2_id":"10729","normalized":[]},{"id":"10734","type":"CID","arg1_id":"10716","arg2_id":"10721","normalized":[]},{"id":"10735","type":"CID","arg1_id":"10716","arg2_id":"10728","normalized":[]},{"id":"10736","type":"CID","arg1_id":"10716","arg2_id":"10730","normalized":[]},{"id":"10737","type":"CID","arg1_id":"10720","arg2_id":"10721","normalized":[]},{"id":"10738","type":"CID","arg1_id":"10720","arg2_id":"10728","normalized":[]},{"id":"10739","type":"CID","arg1_id":"10720","arg2_id":"10730","normalized":[]},{"id":"10740","type":"CID","arg1_id":"10722","arg2_id":"10721","normalized":[]},{"id":"10741","type":"CID","arg1_id":"10722","arg2_id":"10728","normalized":[]},{"id":"10742","type":"CID","arg1_id":"10722","arg2_id":"10730","normalized":[]}]}
{"id":"10743","document_id":"9249847","passages":[{"id":"10744","type":"title","text":["Iatrogenically induced intractable atrioventricular reentrant tachycardia after verapamil and catheter ablation in a patient with Wolff-Parkinson-White syndrome and idiopathic dilated cardiomyopathy."],"offsets":[[0,199]]},{"id":"10745","type":"abstract","text":["In a patient with WPW syndrome and idiopathic dilated cardiomyopathy, intractable atrioventricular reentrant tachycardia (AVRT) was iatrogenically induced. QRS without preexcitation, caused by junctional escape beats after verapamil or unidirectional antegrade block of accessory pathway after catheter ablation, established frequent AVRT attack."],"offsets":[[200,546]]}],"entities":[{"id":"10746","type":"Disease","text":["atrioventricular reentrant tachycardia"],"offsets":[[35,73]],"normalized":[{"db_name":"MESH","db_id":"D013611"}]},{"id":"10747","type":"Chemical","text":["verapamil"],"offsets":[[80,89]],"normalized":[{"db_name":"MESH","db_id":"D014700"}]},{"id":"10748","type":"Disease","text":["Wolff-Parkinson-White syndrome"],"offsets":[[130,160]],"normalized":[{"db_name":"MESH","db_id":"D014927"}]},{"id":"10749","type":"Disease","text":["idiopathic dilated cardiomyopathy"],"offsets":[[165,198]],"normalized":[{"db_name":"MESH","db_id":"D002311"}]},{"id":"10750","type":"Disease","text":["WPW syndrome"],"offsets":[[218,230]],"normalized":[{"db_name":"MESH","db_id":"D014927"}]},{"id":"10751","type":"Disease","text":["idiopathic dilated cardiomyopathy"],"offsets":[[235,268]],"normalized":[{"db_name":"MESH","db_id":"D002311"}]},{"id":"10752","type":"Disease","text":["atrioventricular reentrant tachycardia"],"offsets":[[282,320]],"normalized":[{"db_name":"MESH","db_id":"D013611"}]},{"id":"10753","type":"Disease","text":["AVRT"],"offsets":[[322,326]],"normalized":[{"db_name":"MESH","db_id":"D013611"}]},{"id":"10754","type":"Chemical","text":["verapamil"],"offsets":[[423,432]],"normalized":[{"db_name":"MESH","db_id":"D014700"}]},{"id":"10755","type":"Disease","text":["AVRT"],"offsets":[[534,538]],"normalized":[{"db_name":"MESH","db_id":"D013611"}]}],"events":[],"coreferences":[],"relations":[{"id":"10756","type":"CID","arg1_id":"10747","arg2_id":"10746","normalized":[]},{"id":"10757","type":"CID","arg1_id":"10747","arg2_id":"10752","normalized":[]},{"id":"10758","type":"CID","arg1_id":"10747","arg2_id":"10753","normalized":[]},{"id":"10759","type":"CID","arg1_id":"10747","arg2_id":"10755","normalized":[]},{"id":"10760","type":"CID","arg1_id":"10754","arg2_id":"10746","normalized":[]},{"id":"10761","type":"CID","arg1_id":"10754","arg2_id":"10752","normalized":[]},{"id":"10762","type":"CID","arg1_id":"10754","arg2_id":"10753","normalized":[]},{"id":"10763","type":"CID","arg1_id":"10754","arg2_id":"10755","normalized":[]}]}
{"id":"10764","document_id":"9284778","passages":[{"id":"10765","type":"title","text":["Epidemic of liver disease caused by hydrochlorofluorocarbons used as ozone-sparing substitutes of chlorofluorocarbons."],"offsets":[[0,118]]},{"id":"10766","type":"abstract","text":["BACKGROUND: Hydrochlorofluorocarbons (HCFCs) are used increasingly in industry as substitutes for ozone-depleting chlorofluorocarbons (CFCs). Limited studies in animals indicate potential hepatotoxicity of some of these compounds. We investigated an epidemic of liver disease in nine industrial workers who had had repeated accidental exposure to a mixture of 1,1-dichloro-2,2,2-trifluoroethane (HCFC 123) and 1-chloro-1,2,2,2-tetrafluoroethane (HCFC 124). All nine exposed workers were affected to various degrees. Both compounds are metabolised in the same way as 1-bromo-1-chloro-2,2,2-trifluoroethane (halothane) to form reactive trifluoroacetyl halide intermediates, which have been implicated in the hepatotoxicity of halothane. We aimed to test whether HCFCs 123 and 124 can result in serious liver disease. METHODS: For one severely affected worker liver biopsy and immunohistochemical stainings for the presence of trifluoroacetyl protein adducts were done. The serum of six affected workers and five controls was tested for autoantibodies that react with human liver cytochrome-P450 2E1 (P450 2E1) and P58 protein disulphide isomerase isoform (P58). FINDINGS: The liver biopsy sample showed hepatocellular necrosis which was prominent in perivenular zone three and extended focally from portal tracts to portal tracts and centrilobular areas (bridging necrosis). Trifluoroacetyl-adducted proteins were detected in surviving hepatocytes. Autoantibodies against P450 2E1 or P58, previously associated with halothane hepatitis, were detected in the serum of five affected workers. INTERPRETATION: Repeated exposure of human beings to HCFCs 123 and 124 can result in serious liver injury in a large proportion of the exposed population. Although the exact mechanism of hepatotoxicity of these agents is not known, the results suggest that trifluoroacetyl-altered liver proteins are involved. In view of the potentially widespread use of these compounds, there is an urgent need to develop safer alternatives."],"offsets":[[119,2133]]}],"entities":[{"id":"10767","type":"Disease","text":["liver 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124"],"offsets":[[565,573]],"normalized":[{"db_name":"MESH","db_id":"C072959"}]},{"id":"10782","type":"Chemical","text":["1-bromo-1-chloro-2,2,2-trifluoroethane"],"offsets":[[685,723]],"normalized":[{"db_name":"MESH","db_id":"D006221"}]},{"id":"10783","type":"Chemical","text":["halothane"],"offsets":[[725,734]],"normalized":[{"db_name":"MESH","db_id":"D006221"}]},{"id":"10784","type":"Chemical","text":["trifluoroacetyl"],"offsets":[[753,768]],"normalized":[{"db_name":"MESH","db_id":"D014269"}]},{"id":"10785","type":"Disease","text":["hepatotoxicity"],"offsets":[[825,839]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"10786","type":"Chemical","text":["halothane"],"offsets":[[843,852]],"normalized":[{"db_name":"MESH","db_id":"D006221"}]},{"id":"10787","type":"Chemical","text":["HCFCs 123 and 124"],"offsets":[[879,896]],"normalized":[{"db_name":"MESH","db_id":"C067411"},{"db_name":"MESH","db_id":"C072959"}]},{"id":"10788","type":"Chemical","text":["HCFCs 123"],"offsets":[[879,888]],"normalized":[{"db_name":"MESH","db_id":"C067411"}]},{"id":"10789","type":"Chemical","text":["HCFCs","124"],"offsets":[[879,884],[893,896]],"normalized":[{"db_name":"MESH","db_id":"C072959"}]},{"id":"10790","type":"Disease","text":["liver disease"],"offsets":[[919,932]],"normalized":[{"db_name":"MESH","db_id":"D008107"}]},{"id":"10791","type":"Chemical","text":["trifluoroacetyl"],"offsets":[[1043,1058]],"normalized":[{"db_name":"MESH","db_id":"D014269"}]},{"id":"10792","type":"Disease","text":["necrosis"],"offsets":[[1335,1343]],"normalized":[{"db_name":"MESH","db_id":"D009336"}]},{"id":"10793","type":"Disease","text":["necrosis"],"offsets":[[1481,1489]],"normalized":[{"db_name":"MESH","db_id":"D009336"}]},{"id":"10794","type":"Chemical","text":["Trifluoroacetyl"],"offsets":[[1492,1507]],"normalized":[{"db_name":"MESH","db_id":"D014269"}]},{"id":"10795","type":"Disease","text":["halothane hepatitis"],"offsets":[[1633,1652]],"normalized":[{"db_name":"MESH","db_id":"C562477"}]},{"id":"10796","type":"Chemical","text":["HCFCs 123 and 124"],"offsets":[[1760,1777]],"normalized":[{"db_name":"MESH","db_id":"C067411"},{"db_name":"MESH","db_id":"C072959"}]},{"id":"10797","type":"Chemical","text":["HCFCs 123"],"offsets":[[1760,1769]],"normalized":[{"db_name":"MESH","db_id":"C067411"}]},{"id":"10798","type":"Chemical","text":["HCFCs","124"],"offsets":[[1760,1765],[1774,1777]],"normalized":[{"db_name":"MESH","db_id":"C072959"}]},{"id":"10799","type":"Disease","text":["liver injury"],"offsets":[[1800,1812]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"10800","type":"Disease","text":["hepatotoxicity"],"offsets":[[1894,1908]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"10801","type":"Chemical","text":["trifluoroacetyl"],"offsets":[[1964,1979]],"normalized":[{"db_name":"MESH","db_id":"D014269"}]}],"events":[],"coreferences":[],"relations":[{"id":"10802","type":"CID","arg1_id":"10780","arg2_id":"10767","normalized":[]},{"id":"10803","type":"CID","arg1_id":"10780","arg2_id":"10777","normalized":[]},{"id":"10804","type":"CID","arg1_id":"10780","arg2_id":"10790","normalized":[]},{"id":"10805","type":"CID","arg1_id":"10781","arg2_id":"10767","normalized":[]},{"id":"10806","type":"CID","arg1_id":"10781","arg2_id":"10777","normalized":[]},{"id":"10807","type":"CID","arg1_id":"10781","arg2_id":"10790","normalized":[]},{"id":"10808","type":"CID","arg1_id":"10787","arg2_id":"10767","normalized":[]},{"id":"10809","type":"CID","arg1_id":"10787","arg2_id":"10777","normalized":[]},{"id":"10810","type":"CID","arg1_id":"10787","arg2_id":"10790","normalized":[]},{"id":"10811","type":"CID","arg1_id":"10789","arg2_id":"10767","normalized":[]},{"id":"10812","type":"CID","arg1_id":"10789","arg2_id":"10777","normalized":[]},{"id":"10813","type":"CID","arg1_id":"10789","arg2_id":"10790","normalized":[]},{"id":"10814","type":"CID","arg1_id":"10796","arg2_id":"10767","normalized":[]},{"id":"10815","type":"CID","arg1_id":"10796","arg2_id":"10777","normalized":[]},{"id":"10816","type":"CID","arg1_id":"10796","arg2_id":"10790","normalized":[]},{"id":"10817","type":"CID","arg1_id":"10798","arg2_id":"10767","normalized":[]},{"id":"10818","type":"CID","arg1_id":"10798","arg2_id":"10777","normalized":[]},{"id":"10819","type":"CID","arg1_id":"10798","arg2_id":"10790","normalized":[]},{"id":"10820","type":"CID","arg1_id":"10778","arg2_id":"10767","normalized":[]},{"id":"10821","type":"CID","arg1_id":"10778","arg2_id":"10777","normalized":[]},{"id":"10822","type":"CID","arg1_id":"10778","arg2_id":"10790","normalized":[]},{"id":"10823","type":"CID","arg1_id":"10779","arg2_id":"10767","normalized":[]},{"id":"10824","type":"CID","arg1_id":"10779","arg2_id":"10777","normalized":[]},{"id":"10825","type":"CID","arg1_id":"10779","arg2_id":"10790","normalized":[]},{"id":"10826","type":"CID","arg1_id":"10787","arg2_id":"10767","normalized":[]},{"id":"10827","type":"CID","arg1_id":"10787","arg2_id":"10777","normalized":[]},{"id":"10828","type":"CID","arg1_id":"10787","arg2_id":"10790","normalized":[]},{"id":"10829","type":"CID","arg1_id":"10788","arg2_id":"10767","normalized":[]},{"id":"10830","type":"CID","arg1_id":"10788","arg2_id":"10777","normalized":[]},{"id":"10831","type":"CID","arg1_id":"10788","arg2_id":"10790","normalized":[]},{"id":"10832","type":"CID","arg1_id":"10796","arg2_id":"10767","normalized":[]},{"id":"10833","type":"CID","arg1_id":"10796","arg2_id":"10777","normalized":[]},{"id":"10834","type":"CID","arg1_id":"10796","arg2_id":"10790","normalized":[]},{"id":"10835","type":"CID","arg1_id":"10797","arg2_id":"10767","normalized":[]},{"id":"10836","type":"CID","arg1_id":"10797","arg2_id":"10777","normalized":[]},{"id":"10837","type":"CID","arg1_id":"10797","arg2_id":"10790","normalized":[]}]}
{"id":"10838","document_id":"9522143","passages":[{"id":"10839","type":"title","text":["The effect of different anaesthetic agents in hearing loss following spinal anaesthesia."],"offsets":[[0,88]]},{"id":"10840","type":"abstract","text":["The cause of hearing loss after spinal anaesthesia is unknown. Up until now, the only factor studied has been the effect of the diameter of the spinal needle on post-operative sensorineural hearing loss. The aim of this study was to describe this hearing loss and to investigate other factors influencing the degree of hearing loss. Two groups of 22 similar patients were studied: one group received 6 mL prilocaine 2%; and the other received 3 mL bupivacaine 0.5%. Patients given prilocaine were more likely to develop hearing loss (10 out of 22) than those given bupivacaine (4 out of 22) (P < 0.05). The average hearing loss for speech frequencies was about 10 dB after prilocaine and 15 dB after bupivacaine. None of the patients complained of subjective hearing loss. Long-term follow-up of the patients was not possible."],"offsets":[[89,915]]}],"entities":[{"id":"10841","type":"Disease","text":["hearing loss"],"offsets":[[46,58]],"normalized":[{"db_name":"MESH","db_id":"D034381"}]},{"id":"10842","type":"Disease","text":["hearing loss"],"offsets":[[102,114]],"normalized":[{"db_name":"MESH","db_id":"D034381"}]},{"id":"10843","type":"Disease","text":["sensorineural hearing loss"],"offsets":[[265,291]],"normalized":[{"db_name":"MESH","db_id":"D006319"}]},{"id":"10844","type":"Disease","text":["hearing loss"],"offsets":[[336,348]],"normalized":[{"db_name":"MESH","db_id":"D034381"}]},{"id":"10845","type":"Disease","text":["hearing 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{"id":"10897","document_id":"9522152","passages":[{"id":"10898","type":"title","text":["A transient neurological deficit following intrathecal injection of 1% hyperbaric bupivacaine for unilateral spinal anaesthesia."],"offsets":[[0,128]]},{"id":"10899","type":"abstract","text":["We describe a case of transient neurological deficit that occurred after unilateral spinal anaesthesia with 8 mg of 1% hyperbaric bupivacaine slowly injected through a 25-gauge pencil-point spinal needle. The surgery and anaesthesia were uneventful, but 3 days after surgery, the patient reported an area of hypoaesthesia over L3-L4 dermatomes of the leg which had been operated on (loss of pinprick sensation) without reduction in muscular strength. Sensation in this area returned to normal over the following 2 weeks. Prospective multicentre studies with a large population and a long follow-up should be performed in order to evaluate the incidence of this unusual side effect. However, we suggest that a low solution concentration should be preferred for unilateral spinal anaesthesia with a hyperbaric anaesthetic solution (if pencil-point needle and slow injection rate are employed), in order to minimize the risk of a localized high peak anaesthetic concentration, which might lead to a transient neurological deficit."],"offsets":[[129,1156]]}],"entities":[{"id":"10900","type":"Disease","text":["neurological deficit"],"offsets":[[12,32]],"normalized":[{"db_name":"MESH","db_id":"D009461"}]},{"id":"10901","type":"Chemical","text":["bupivacaine"],"offsets":[[82,93]],"normalized":[{"db_name":"MESH","db_id":"D002045"}]},{"id":"10902","type":"Disease","text":["neurological deficit"],"offsets":[[161,181]],"normalized":[{"db_name":"MESH","db_id":"D009461"}]},{"id":"10903","type":"Chemical","text":["bupivacaine"],"offsets":[[259,270]],"normalized":[{"db_name":"MESH","db_id":"D002045"}]},{"id":"10904","type":"Disease","text":["loss of pinprick sensation"],"offsets":[[512,538]],"normalized":[{"db_name":"MESH","db_id":"D012678"}]},{"id":"10905","type":"Disease","text":["neurological deficit"],"offsets":[[1135,1155]],"normalized":[{"db_name":"MESH","db_id":"D009461"}]}],"events":[],"coreferences":[],"relations":[{"id":"10906","type":"CID","arg1_id":"10901","arg2_id":"10904","normalized":[]},{"id":"10907","type":"CID","arg1_id":"10903","arg2_id":"10904","normalized":[]}]}
{"id":"10908","document_id":"9672936","passages":[{"id":"10909","type":"title","text":["Pethidine-associated seizure in a healthy adolescent receiving pethidine for postoperative pain control."],"offsets":[[0,104]]},{"id":"10910","type":"abstract","text":["A healthy 17-year-old male received standard intermittent doses of pethidine via a patient-controlled analgesia (PCA) pump for management of postoperative pain control. Twenty-three h postoperatively he developed a brief self-limited seizure. Both plasma pethidine and norpethidine were elevated in the range associated with clinical manifestations of central nervous system excitation. No other risk factors for CNS toxicity were identified. This method allowed frequent self-dosing of pethidine at short time intervals and rapid accumulation of pethidine and norpethidine. The routine use of pethidine via PCA even for a brief postoperative analgesia should be reconsidered."],"offsets":[[105,781]]}],"entities":[{"id":"10911","type":"Chemical","text":["Pethidine"],"offsets":[[0,9]],"normalized":[{"db_name":"MESH","db_id":"D008614"}]},{"id":"10912","type":"Disease","text":["seizure"],"offsets":[[21,28]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"10913","type":"Chemical","text":["pethidine"],"offsets":[[63,72]],"normalized":[{"db_name":"MESH","db_id":"D008614"}]},{"id":"10914","type":"Disease","text":["postoperative pain"],"offsets":[[77,95]],"normalized":[{"db_name":"MESH","db_id":"D010149"}]},{"id":"10915","type":"Chemical","text":["pethidine"],"offsets":[[172,181]],"normalized":[{"db_name":"MESH","db_id":"D008614"}]},{"id":"10916","type":"Disease","text":["postoperative pain"],"offsets":[[246,264]],"normalized":[{"db_name":"MESH","db_id":"D010149"}]},{"id":"10917","type":"Disease","text":["seizure"],"offsets":[[339,346]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"10918","type":"Chemical","text":["pethidine"],"offsets":[[360,369]],"normalized":[{"db_name":"MESH","db_id":"D008614"}]},{"id":"10919","type":"Chemical","text":["norpethidine"],"offsets":[[374,386]],"normalized":[{"db_name":"MESH","db_id":"C002752"}]},{"id":"10920","type":"Disease","text":["toxicity"],"offsets":[[522,530]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"10921","type":"Chemical","text":["pethidine"],"offsets":[[592,601]],"normalized":[{"db_name":"MESH","db_id":"D008614"}]},{"id":"10922","type":"Chemical","text":["pethidine"],"offsets":[[652,661]],"normalized":[{"db_name":"MESH","db_id":"D008614"}]},{"id":"10923","type":"Chemical","text":["norpethidine"],"offsets":[[666,678]],"normalized":[{"db_name":"MESH","db_id":"C002752"}]},{"id":"10924","type":"Chemical","text":["pethidine"],"offsets":[[699,708]],"normalized":[{"db_name":"MESH","db_id":"D008614"}]}],"events":[],"coreferences":[],"relations":[{"id":"10925","type":"CID","arg1_id":"10911","arg2_id":"10912","normalized":[]},{"id":"10926","type":"CID","arg1_id":"10911","arg2_id":"10917","normalized":[]},{"id":"10927","type":"CID","arg1_id":"10913","arg2_id":"10912","normalized":[]},{"id":"10928","type":"CID","arg1_id":"10913","arg2_id":"10917","normalized":[]},{"id":"10929","type":"CID","arg1_id":"10915","arg2_id":"10912","normalized":[]},{"id":"10930","type":"CID","arg1_id":"10915","arg2_id":"10917","normalized":[]},{"id":"10931","type":"CID","arg1_id":"10918","arg2_id":"10912","normalized":[]},{"id":"10932","type":"CID","arg1_id":"10918","arg2_id":"10917","normalized":[]},{"id":"10933","type":"CID","arg1_id":"10921","arg2_id":"10912","normalized":[]},{"id":"10934","type":"CID","arg1_id":"10921","arg2_id":"10917","normalized":[]},{"id":"10935","type":"CID","arg1_id":"10922","arg2_id":"10912","normalized":[]},{"id":"10936","type":"CID","arg1_id":"10922","arg2_id":"10917","normalized":[]},{"id":"10937","type":"CID","arg1_id":"10924","arg2_id":"10912","normalized":[]},{"id":"10938","type":"CID","arg1_id":"10924","arg2_id":"10917","normalized":[]}]}
{"id":"10939","document_id":"9721172","passages":[{"id":"10940","type":"title","text":["Drug-associated acute-onset vanishing bile duct and Stevens-Johnson syndromes in a child."],"offsets":[[0,89]]},{"id":"10941","type":"abstract","text":["Acute vanishing bile duct syndrome is a rare but established cause of progressive cholestasis in adults, is most often drug or toxin related, and is of unknown pathogenesis. It has not been reported previously in children. Stevens-Johnson syndrome is a well-recognized immune complex-mediated hypersensitivity reaction that affects all age groups, is drug or infection induced, and has classic systemic, mucosal, and dermatologic manifestations. A previously healthy child who developed acute, severe, rapidly progressive vanishing bile duct syndrome shortly after Stevens-Johnson syndrome is described; this was temporally associated with ibuprofen use. Despite therapy with ursodeoxycholic acid, prednisone, and then tacrolimus, her cholestatic disease was unrelenting, with cirrhosis shown by biopsy 6 months after presentation. This case documents acute drug-related vanishing bile duct syndrome in the pediatric age group and suggests shared immune mechanisms in the pathogenesis of both Stevens-Johnson syndrome and vanishing bile duct syndrome."],"offsets":[[90,1141]]}],"entities":[{"id":"10942","type":"Disease","text":["vanishing bile duct"],"offsets":[[28,47]],"normalized":[{"db_name":"MESH","db_id":"D001649"}]},{"id":"10943","type":"Disease","text":["Stevens-Johnson syndromes"],"offsets":[[52,77]],"normalized":[{"db_name":"MESH","db_id":"D013262"}]},{"id":"10944","type":"Disease","text":["vanishing bile duct"],"offsets":[[96,115]],"normalized":[{"db_name":"MESH","db_id":"D001649"}]},{"id":"10945","type":"Disease","text":["cholestasis"],"offsets":[[172,183]],"normalized":[{"db_name":"MESH","db_id":"D002779"}]},{"id":"10946","type":"Disease","text":["Stevens-Johnson syndrome"],"offsets":[[313,337]],"normalized":[{"db_name":"MESH","db_id":"D013262"}]},{"id":"10947","type":"Disease","text":["hypersensitivity"],"offsets":[[383,399]],"normalized":[{"db_name":"MESH","db_id":"D004342"}]},{"id":"10948","type":"Disease","text":["infection"],"offsets":[[449,458]],"normalized":[{"db_name":"MESH","db_id":"D007239"}]},{"id":"10949","type":"Disease","text":["vanishing bile duct syndrome"],"offsets":[[612,640]],"normalized":[{"db_name":"MESH","db_id":"D001649"}]},{"id":"10950","type":"Disease","text":["Stevens-Johnson syndrome"],"offsets":[[655,679]],"normalized":[{"db_name":"MESH","db_id":"D013262"}]},{"id":"10951","type":"Chemical","text":["ibuprofen"],"offsets":[[730,739]],"normalized":[{"db_name":"MESH","db_id":"D007052"}]},{"id":"10952","type":"Chemical","text":["ursodeoxycholic acid"],"offsets":[[766,786]],"normalized":[{"db_name":"MESH","db_id":"D014580"}]},{"id":"10953","type":"Chemical","text":["prednisone"],"offsets":[[788,798]],"normalized":[{"db_name":"MESH","db_id":"D011241"}]},{"id":"10954","type":"Chemical","text":["tacrolimus"],"offsets":[[809,819]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"10955","type":"Disease","text":["cholestatic disease"],"offsets":[[825,844]],"normalized":[{"db_name":"MESH","db_id":"D002779"}]},{"id":"10956","type":"Disease","text":["cirrhosis"],"offsets":[[867,876]],"normalized":[{"db_name":"MESH","db_id":"D005355"}]},{"id":"10957","type":"Disease","text":["vanishing bile duct syndrome"],"offsets":[[961,989]],"normalized":[{"db_name":"MESH","db_id":"D001649"}]},{"id":"10958","type":"Disease","text":["Stevens-Johnson syndrome"],"offsets":[[1083,1107]],"normalized":[{"db_name":"MESH","db_id":"D013262"}]},{"id":"10959","type":"Disease","text":["vanishing bile duct syndrome"],"offsets":[[1112,1140]],"normalized":[{"db_name":"MESH","db_id":"D001649"}]}],"events":[],"coreferences":[],"relations":[{"id":"10960","type":"CID","arg1_id":"10951","arg2_id":"10943","normalized":[]},{"id":"10961","type":"CID","arg1_id":"10951","arg2_id":"10946","normalized":[]},{"id":"10962","type":"CID","arg1_id":"10951","arg2_id":"10950","normalized":[]},{"id":"10963","type":"CID","arg1_id":"10951","arg2_id":"10958","normalized":[]},{"id":"10964","type":"CID","arg1_id":"10951","arg2_id":"10945","normalized":[]},{"id":"10965","type":"CID","arg1_id":"10951","arg2_id":"10955","normalized":[]}]}
{"id":"10966","document_id":"9727773","passages":[{"id":"10967","type":"title","text":["High incidence of primary pulmonary hypertension associated with appetite suppressants in Belgium."],"offsets":[[0,98]]},{"id":"10968","type":"abstract","text":["Primary pulmonary hypertension is a rare, progressive and incurable disease, which has been associated with the intake of appetite suppressant drugs. The importance of this association was evaluated in Belgium while this country still had no restriction on the prescription of appetite suppressants. Thirty-five patients with primary pulmonary hypertension and 85 matched controls were recruited over 32 months (1992-1994) in Belgium. Exposure to appetite-suppressants was assessed on the basis of hospital records and standardized interview. Twenty-three of the patients had previously taken appetite suppressants, mainly fenfluramines, as compared with only 5 of the controls (66 versus 6%, p<0.0001). Five patients died before the interview, all of them had taken appetite suppressants. In 8 patients the diagnosis of primary pulmonary hypertension was uncertain, 5 of them had taken appetite suppressants. The patients who had been exposed to appetite suppressants tended to be on average more severely ill, and to have a shorter median delay between onset of symptoms and diagnosis. A policy of unrestricted prescription of appetite suppressants may lead to a high incidence of associated primary pulmonary hypertension. Intake of appetite suppressants may accelerate the progression of the disease."],"offsets":[[99,1403]]}],"entities":[{"id":"10969","type":"Disease","text":["primary pulmonary hypertension"],"offsets":[[18,48]],"normalized":[{"db_name":"MESH","db_id":"D006976"}]},{"id":"10970","type":"Chemical","text":["appetite suppressants"],"offsets":[[65,86]],"normalized":[{"db_name":"MESH","db_id":"D001067"}]},{"id":"10971","type":"Disease","text":["Primary pulmonary hypertension"],"offsets":[[99,129]],"normalized":[{"db_name":"MESH","db_id":"D006976"}]},{"id":"10972","type":"Chemical","text":["appetite suppressant"],"offsets":[[221,241]],"normalized":[{"db_name":"MESH","db_id":"D001067"}]},{"id":"10973","type":"Chemical","text":["appetite suppressants"],"offsets":[[376,397]],"normalized":[{"db_name":"MESH","db_id":"D001067"}]},{"id":"10974","type":"Disease","text":["primary pulmonary hypertension"],"offsets":[[425,455]],"normalized":[{"db_name":"MESH","db_id":"D006976"}]},{"id":"10975","type":"Chemical","text":["appetite-suppressants"],"offsets":[[546,567]],"normalized":[{"db_name":"MESH","db_id":"D001067"}]},{"id":"10976","type":"Chemical","text":["appetite suppressants"],"offsets":[[692,713]],"normalized":[{"db_name":"MESH","db_id":"D001067"}]},{"id":"10977","type":"Chemical","text":["fenfluramines"],"offsets":[[722,735]],"normalized":[{"db_name":"MESH","db_id":"D005277"}]},{"id":"10978","type":"Chemical","text":["appetite suppressants"],"offsets":[[866,887]],"normalized":[{"db_name":"MESH","db_id":"D001067"}]},{"id":"10979","type":"Disease","text":["primary pulmonary hypertension"],"offsets":[[920,950]],"normalized":[{"db_name":"MESH","db_id":"D006976"}]},{"id":"10980","type":"Chemical","text":["appetite suppressants"],"offsets":[[986,1007]],"normalized":[{"db_name":"MESH","db_id":"D001067"}]},{"id":"10981","type":"Chemical","text":["appetite suppressants"],"offsets":[[1046,1067]],"normalized":[{"db_name":"MESH","db_id":"D001067"}]},{"id":"10982","type":"Chemical","text":["appetite suppressants"],"offsets":[[1228,1249]],"normalized":[{"db_name":"MESH","db_id":"D001067"}]},{"id":"10983","type":"Disease","text":["primary pulmonary hypertension"],"offsets":[[1293,1323]],"normalized":[{"db_name":"MESH","db_id":"D006976"}]},{"id":"10984","type":"Chemical","text":["appetite suppressants"],"offsets":[[1335,1356]],"normalized":[{"db_name":"MESH","db_id":"D001067"}]}],"events":[],"coreferences":[],"relations":[{"id":"10985","type":"CID","arg1_id":"10977","arg2_id":"10969","normalized":[]},{"id":"10986","type":"CID","arg1_id":"10977","arg2_id":"10971","normalized":[]},{"id":"10987","type":"CID","arg1_id":"10977","arg2_id":"10974","normalized":[]},{"id":"10988","type":"CID","arg1_id":"10977","arg2_id":"10979","normalized":[]},{"id":"10989","type":"CID","arg1_id":"10977","arg2_id":"10983","normalized":[]},{"id":"10990","type":"CID","arg1_id":"10970","arg2_id":"10969","normalized":[]},{"id":"10991","type":"CID","arg1_id":"10970","arg2_id":"10971","normalized":[]},{"id":"10992","type":"CID","arg1_id":"10970","arg2_id":"10974","normalized":[]},{"id":"10993","type":"CID","arg1_id":"10970","arg2_id":"10979","normalized":[]},{"id":"10994","type":"CID","arg1_id":"10970","arg2_id":"10983","normalized":[]},{"id":"10995","type":"CID","arg1_id":"10972","arg2_id":"10969","normalized":[]},{"id":"10996","type":"CID","arg1_id":"10972","arg2_id":"10971","normalized":[]},{"id":"10997","type":"CID","arg1_id":"10972","arg2_id":"10974","normalized":[]},{"id":"10998","type":"CID","arg1_id":"10972","arg2_id":"10979","normalized":[]},{"id":"10999","type":"CID","arg1_id":"10972","arg2_id":"10983","normalized":[]},{"id":"11000","type":"CID","arg1_id":"10973","arg2_id":"10969","normalized":[]},{"id":"11001","type":"CID","arg1_id":"10973","arg2_id":"10971","normalized":[]},{"id":"11002","type":"CID","arg1_id":"10973","arg2_id":"10974","normalized":[]},{"id":"11003","type":"CID","arg1_id":"10973","arg2_id":"10979","normalized":[]},{"id":"11004","type":"CID","arg1_id":"10973","arg2_id":"10983","normalized":[]},{"id":"11005","type":"CID","arg1_id":"10975","arg2_id":"10969","normalized":[]},{"id":"11006","type":"CID","arg1_id":"10975","arg2_id":"10971","normalized":[]},{"id":"11007","type":"CID","arg1_id":"10975","arg2_id":"10974","normalized":[]},{"id":"11008","type":"CID","arg1_id":"10975","arg2_id":"10979","normalized":[]},{"id":"11009","type":"CID","arg1_id":"10975","arg2_id":"10983","normalized":[]},{"id":"11010","type":"CID","arg1_id":"10976","arg2_id":"10969","normalized":[]},{"id":"11011","type":"CID","arg1_id":"10976","arg2_id":"10971","normalized":[]},{"id":"11012","type":"CID","arg1_id":"10976","arg2_id":"10974","normalized":[]},{"id":"11013","type":"CID","arg1_id":"10976","arg2_id":"10979","normalized":[]},{"id":"11014","type":"CID","arg1_id":"10976","arg2_id":"10983","normalized":[]},{"id":"11015","type":"CID","arg1_id":"10978","arg2_id":"10969","normalized":[]},{"id":"11016","type":"CID","arg1_id":"10978","arg2_id":"10971","normalized":[]},{"id":"11017","type":"CID","arg1_id":"10978","arg2_id":"10974","normalized":[]},{"id":"11018","type":"CID","arg1_id":"10978","arg2_id":"10979","normalized":[]},{"id":"11019","type":"CID","arg1_id":"10978","arg2_id":"10983","normalized":[]},{"id":"11020","type":"CID","arg1_id":"10980","arg2_id":"10969","normalized":[]},{"id":"11021","type":"CID","arg1_id":"10980","arg2_id":"10971","normalized":[]},{"id":"11022","type":"CID","arg1_id":"10980","arg2_id":"10974","normalized":[]},{"id":"11023","type":"CID","arg1_id":"10980","arg2_id":"10979","normalized":[]},{"id":"11024","type":"CID","arg1_id":"10980","arg2_id":"10983","normalized":[]},{"id":"11025","type":"CID","arg1_id":"10981","arg2_id":"10969","normalized":[]},{"id":"11026","type":"CID","arg1_id":"10981","arg2_id":"10971","normalized":[]},{"id":"11027","type":"CID","arg1_id":"10981","arg2_id":"10974","normalized":[]},{"id":"11028","type":"CID","arg1_id":"10981","arg2_id":"10979","normalized":[]},{"id":"11029","type":"CID","arg1_id":"10981","arg2_id":"10983","normalized":[]},{"id":"11030","type":"CID","arg1_id":"10982","arg2_id":"10969","normalized":[]},{"id":"11031","type":"CID","arg1_id":"10982","arg2_id":"10971","normalized":[]},{"id":"11032","type":"CID","arg1_id":"10982","arg2_id":"10974","normalized":[]},{"id":"11033","type":"CID","arg1_id":"10982","arg2_id":"10979","normalized":[]},{"id":"11034","type":"CID","arg1_id":"10982","arg2_id":"10983","normalized":[]},{"id":"11035","type":"CID","arg1_id":"10984","arg2_id":"10969","normalized":[]},{"id":"11036","type":"CID","arg1_id":"10984","arg2_id":"10971","normalized":[]},{"id":"11037","type":"CID","arg1_id":"10984","arg2_id":"10974","normalized":[]},{"id":"11038","type":"CID","arg1_id":"10984","arg2_id":"10979","normalized":[]},{"id":"11039","type":"CID","arg1_id":"10984","arg2_id":"10983","normalized":[]}]}
{"id":"11040","document_id":"9754849","passages":[{"id":"11041","type":"title","text":["Choreoathetoid movements associated with rapid adjustment to methadone."],"offsets":[[0,71]]},{"id":"11042","type":"abstract","text":["Choreatiform hyperkinesias are known to be occasional movement abnormalities during intoxications with cocaine but not opiates. This is a case report of euphoria and choreoathetoid movements both transiently induced by rapid adjustment to the selective mu-opioid receptor agonist methadone in an inpatient previously abusing heroine and cocaine. In addition, minor EEG abnormalities occurred. Possible underlying neurobiological phenomena are discussed."],"offsets":[[72,525]]}],"entities":[{"id":"11043","type":"Disease","text":["Choreoathetoid movements"],"offsets":[[0,24]],"normalized":[{"db_name":"MESH","db_id":"D002819"}]},{"id":"11044","type":"Chemical","text":["methadone"],"offsets":[[61,70]],"normalized":[{"db_name":"MESH","db_id":"D008691"}]},{"id":"11045","type":"Disease","text":["Choreatiform hyperkinesias"],"offsets":[[72,98]],"normalized":[{"db_name":"MESH","db_id":"D002819"},{"db_name":"MESH","db_id":"D006948"}]},{"id":"11046","type":"Disease","text":["Choreatiform"],"offsets":[[72,84]],"normalized":[{"db_name":"MESH","db_id":"D002819"}]},{"id":"11047","type":"Disease","text":["hyperkinesias"],"offsets":[[85,98]],"normalized":[{"db_name":"MESH","db_id":"D006948"}]},{"id":"11048","type":"Disease","text":["movement abnormalities"],"offsets":[[126,148]],"normalized":[{"db_name":"MESH","db_id":"D020820"}]},{"id":"11049","type":"Chemical","text":["cocaine"],"offsets":[[175,182]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"11050","type":"Disease","text":["choreoathetoid movements"],"offsets":[[238,262]],"normalized":[{"db_name":"MESH","db_id":"D002819"}]},{"id":"11051","type":"Chemical","text":["methadone"],"offsets":[[352,361]],"normalized":[{"db_name":"MESH","db_id":"D008691"}]},{"id":"11052","type":"Chemical","text":["heroine"],"offsets":[[397,404]],"normalized":[{"db_name":"MESH","db_id":"D003932"}]},{"id":"11053","type":"Chemical","text":["cocaine"],"offsets":[[409,416]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]}],"events":[],"coreferences":[],"relations":[{"id":"11054","type":"CID","arg1_id":"11044","arg2_id":"11043","normalized":[]},{"id":"11055","type":"CID","arg1_id":"11044","arg2_id":"11045","normalized":[]},{"id":"11056","type":"CID","arg1_id":"11044","arg2_id":"11046","normalized":[]},{"id":"11057","type":"CID","arg1_id":"11044","arg2_id":"11050","normalized":[]},{"id":"11058","type":"CID","arg1_id":"11051","arg2_id":"11043","normalized":[]},{"id":"11059","type":"CID","arg1_id":"11051","arg2_id":"11045","normalized":[]},{"id":"11060","type":"CID","arg1_id":"11051","arg2_id":"11046","normalized":[]},{"id":"11061","type":"CID","arg1_id":"11051","arg2_id":"11050","normalized":[]},{"id":"11062","type":"CID","arg1_id":"11049","arg2_id":"11045","normalized":[]},{"id":"11063","type":"CID","arg1_id":"11049","arg2_id":"11047","normalized":[]},{"id":"11064","type":"CID","arg1_id":"11053","arg2_id":"11045","normalized":[]},{"id":"11065","type":"CID","arg1_id":"11053","arg2_id":"11047","normalized":[]},{"id":"11066","type":"CID","arg1_id":"11049","arg2_id":"11043","normalized":[]},{"id":"11067","type":"CID","arg1_id":"11049","arg2_id":"11045","normalized":[]},{"id":"11068","type":"CID","arg1_id":"11049","arg2_id":"11046","normalized":[]},{"id":"11069","type":"CID","arg1_id":"11049","arg2_id":"11050","normalized":[]},{"id":"11070","type":"CID","arg1_id":"11053","arg2_id":"11043","normalized":[]},{"id":"11071","type":"CID","arg1_id":"11053","arg2_id":"11045","normalized":[]},{"id":"11072","type":"CID","arg1_id":"11053","arg2_id":"11046","normalized":[]},{"id":"11073","type":"CID","arg1_id":"11053","arg2_id":"11050","normalized":[]}]}
{"id":"11074","document_id":"10365197","passages":[{"id":"11075","type":"title","text":["Cocaine-induced mood disorder: prevalence rates and psychiatric symptoms in an outpatient cocaine-dependent sample."],"offsets":[[0,115]]},{"id":"11076","type":"abstract","text":["This paper attempts to examine and compare prevalence rates and symptom patterns of DSM substance-induced and other mood disorders. 243 cocaine-dependent outpatients with cocaine-induced mood disorder (CIMD), other mood disorders, or no mood disorder were compared on measures of psychiatric symptoms. The prevalence rate for CIMD was 12% at baseline. Introduction of the DSM-IV diagnosis of CIMD did not substantially affect rates of the other depressive disorders. Patients with CIMD had symptom severity levels between those of patients with and without a mood disorder. These findings suggest some validity for the new DSM-IV diagnosis of CIMD, but also suggest that it requires further specification and replication."],"offsets":[[116,837]]}],"entities":[{"id":"11077","type":"Chemical","text":["Cocaine"],"offsets":[[0,7]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"11078","type":"Disease","text":["mood disorder"],"offsets":[[16,29]],"normalized":[{"db_name":"MESH","db_id":"D019964"}]},{"id":"11079","type":"Disease","text":["psychiatric"],"offsets":[[52,63]],"normalized":[{"db_name":"MESH","db_id":"D001523"}]},{"id":"11080","type":"Chemical","text":["cocaine"],"offsets":[[90,97]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"11081","type":"Disease","text":["mood disorders"],"offsets":[[232,246]],"normalized":[{"db_name":"MESH","db_id":"D019964"}]},{"id":"11082","type":"Chemical","text":["cocaine"],"offsets":[[252,259]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"11083","type":"Chemical","text":["cocaine"],"offsets":[[287,294]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"11084","type":"Disease","text":["mood disorder"],"offsets":[[303,316]],"normalized":[{"db_name":"MESH","db_id":"D019964"}]},{"id":"11085","type":"Disease","text":["CIMD"],"offsets":[[318,322]],"normalized":[{"db_name":"MESH","db_id":"D019970"}]},{"id":"11086","type":"Disease","text":["mood disorders"],"offsets":[[331,345]],"normalized":[{"db_name":"MESH","db_id":"D019964"}]},{"id":"11087","type":"Disease","text":["mood disorder"],"offsets":[[353,366]],"normalized":[{"db_name":"MESH","db_id":"D019964"}]},{"id":"11088","type":"Disease","text":["psychiatric"],"offsets":[[396,407]],"normalized":[{"db_name":"MESH","db_id":"D001523"}]},{"id":"11089","type":"Disease","text":["CIMD"],"offsets":[[442,446]],"normalized":[{"db_name":"MESH","db_id":"D019970"}]},{"id":"11090","type":"Disease","text":["CIMD"],"offsets":[[508,512]],"normalized":[{"db_name":"MESH","db_id":"D019970"}]},{"id":"11091","type":"Disease","text":["depressive disorders"],"offsets":[[561,581]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"11092","type":"Disease","text":["CIMD"],"offsets":[[597,601]],"normalized":[{"db_name":"MESH","db_id":"D019970"}]},{"id":"11093","type":"Disease","text":["mood disorder"],"offsets":[[675,688]],"normalized":[{"db_name":"MESH","db_id":"D019964"}]},{"id":"11094","type":"Disease","text":["CIMD"],"offsets":[[759,763]],"normalized":[{"db_name":"MESH","db_id":"D019970"}]}],"events":[],"coreferences":[],"relations":[{"id":"11095","type":"CID","arg1_id":"11077","arg2_id":"11078","normalized":[]},{"id":"11096","type":"CID","arg1_id":"11077","arg2_id":"11081","normalized":[]},{"id":"11097","type":"CID","arg1_id":"11077","arg2_id":"11084","normalized":[]},{"id":"11098","type":"CID","arg1_id":"11077","arg2_id":"11086","normalized":[]},{"id":"11099","type":"CID","arg1_id":"11077","arg2_id":"11087","normalized":[]},{"id":"11100","type":"CID","arg1_id":"11077","arg2_id":"11093","normalized":[]},{"id":"11101","type":"CID","arg1_id":"11080","arg2_id":"11078","normalized":[]},{"id":"11102","type":"CID","arg1_id":"11080","arg2_id":"11081","normalized":[]},{"id":"11103","type":"CID","arg1_id":"11080","arg2_id":"11084","normalized":[]},{"id":"11104","type":"CID","arg1_id":"11080","arg2_id":"11086","normalized":[]},{"id":"11105","type":"CID","arg1_id":"11080","arg2_id":"11087","normalized":[]},{"id":"11106","type":"CID","arg1_id":"11080","arg2_id":"11093","normalized":[]},{"id":"11107","type":"CID","arg1_id":"11082","arg2_id":"11078","normalized":[]},{"id":"11108","type":"CID","arg1_id":"11082","arg2_id":"11081","normalized":[]},{"id":"11109","type":"CID","arg1_id":"11082","arg2_id":"11084","normalized":[]},{"id":"11110","type":"CID","arg1_id":"11082","arg2_id":"11086","normalized":[]},{"id":"11111","type":"CID","arg1_id":"11082","arg2_id":"11087","normalized":[]},{"id":"11112","type":"CID","arg1_id":"11082","arg2_id":"11093","normalized":[]},{"id":"11113","type":"CID","arg1_id":"11083","arg2_id":"11078","normalized":[]},{"id":"11114","type":"CID","arg1_id":"11083","arg2_id":"11081","normalized":[]},{"id":"11115","type":"CID","arg1_id":"11083","arg2_id":"11084","normalized":[]},{"id":"11116","type":"CID","arg1_id":"11083","arg2_id":"11086","normalized":[]},{"id":"11117","type":"CID","arg1_id":"11083","arg2_id":"11087","normalized":[]},{"id":"11118","type":"CID","arg1_id":"11083","arg2_id":"11093","normalized":[]}]}
{"id":"11119","document_id":"10704919","passages":[{"id":"11120","type":"title","text":["Hemolysis of human erythrocytes induced by tamoxifen is related to disruption of membrane structure."],"offsets":[[0,100]]},{"id":"11121","type":"abstract","text":["Tamoxifen (TAM), the antiestrogenic drug most widely prescribed in the chemotherapy of breast cancer, induces changes in normal discoid shape of erythrocytes and hemolytic anemia. This work evaluates the effects of TAM on isolated human erythrocytes, attempting to identify the underlying mechanisms on TAM-induced hemolytic anemia and the involvement of biomembranes in its cytostatic action mechanisms. TAM induces hemolysis of erythrocytes as a function of concentration. The extension of hemolysis is variable with erythrocyte samples, but 12.5 microM TAM induces total hemolysis of all tested suspensions. Despite inducing extensive erythrocyte lysis, TAM does not shift the osmotic fragility curves of erythrocytes. The hemolytic effect of TAM is prevented by low concentrations of alpha-tocopherol (alpha-T) and alpha-tocopherol acetate (alpha-TAc) (inactivated functional hydroxyl) indicating that TAM-induced hemolysis is not related to oxidative membrane damage. This was further evidenced by absence of oxygen consumption and hemoglobin oxidation both determined in parallel with TAM-induced hemolysis. Furthermore, it was observed that TAM inhibits the peroxidation of human erythrocytes induced by AAPH, thus ruling out TAM-induced cell oxidative stress. Hemolysis caused by TAM was not preceded by the leakage of K(+) from the cells, also excluding a colloid-osmotic type mechanism of hemolysis, according to the effects on osmotic fragility curves. However, TAM induces release of peripheral proteins of membrane-cytoskeleton and cytosol proteins essentially bound to band 3. Either alpha-T or alpha-TAc increases membrane packing and prevents TAM partition into model membranes. These effects suggest that the protection from hemolysis by tocopherols is related to a decreased TAM incorporation in condensed membranes and the structural damage of the erythrocyte membrane is consequently avoided. Therefore, TAM-induced hemolysis results from a structural perturbation of red cell membrane, leading to changes in the framework of the erythrocyte membrane and its cytoskeleton caused by its high partition in the membrane. These defects explain the abnormal erythrocyte shape and decreased mechanical stability promoted by TAM, resulting in hemolytic anemia. Additionally, since membrane leakage is a final stage of cytotoxicity, the disruption of the structural characteristics of biomembranes by TAM may contribute to the multiple mechanisms of its anticancer action."],"offsets":[[101,2585]]}],"entities":[{"id":"11122","type":"Disease","text":["Hemolysis"],"offsets":[[0,9]],"normalized":[{"db_name":"MESH","db_id":"D006461"}]},{"id":"11123","type":"Chemical","text":["tamoxifen"],"offsets":[[43,52]],"normalized":[{"db_name":"MESH","db_id":"D013629"}]},{"id":"11124","type":"Chemical","text":["Tamoxifen"],"offsets":[[101,110]],"normalized":[{"db_name":"MESH","db_id":"D013629"}]},{"id":"11125","type":"Chemical","text":["TAM"],"offsets":[[112,115]],"normalized":[{"db_name":"MESH","db_id":"D013629"}]},{"id":"11126","type":"Disease","text":["breast cancer"],"offsets":[[188,201]],"normalized":[{"db_name":"MESH","db_id":"D001943"}]},{"id":"11127","type":"Disease","text":["hemolytic 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{"id":"11448","document_id":"10706004","passages":[{"id":"11449","type":"title","text":["Changes of sodium and ATP affinities of the cardiac (Na,K)-ATPase during and after nitric oxide deficient hypertension."],"offsets":[[0,119]]},{"id":"11450","type":"abstract","text":["In the cardiovascular system, NO is involved in the regulation of a variety of functions. Inhibition of NO synthesis induces sustained hypertension. In several models of hypertension, elevation of intracellular sodium level was documented in cardiac tissue. To assess the molecular basis of disturbances in transmembraneous transport of Na+, we studied the response of cardiac (Na,K)-ATPase to NO-deficient hypertension induced in rats by NO-synthase inhibition with 40 mg\/kg\/day N(G)-nitro-L-arginine methyl ester (L-NAME) for 4 four weeks. After 4-week administration of L-NAME, the systolic blood pressure (SBP) increased by 36%. Two weeks after terminating the treatment, the SBP recovered to control value. When activating the (Na,K)-ATPase with its substrate ATP, no changes in Km and Vmax values were observed in NO-deficient rats. During activation with Na+, the Vmax remained unchanged, however the K(Na) increased by 50%, indicating a profound decrease in the affinity of the Na+-binding site in NO-deficient rats. After recovery from hypertension, the activity of (Na,K)-ATPase increased, due to higher affinity of the ATP-binding site, as revealed from the lowered Km value for ATP. The K(Na) value for Na+ returned to control value. Inhibition of NO-synthase induced a reversible hypertension accompanied by depressed Na+-extrusion from cardiac cells as a consequence of deteriorated Na+-binding properties of the (Na,K)-ATPase. After recovery of blood pressure to control values, the extrusion of Na+ from cardiac cells was normalized, as revealed by restoration of the (Na,K)-ATPase activity."],"offsets":[[120,1727]]}],"entities":[{"id":"11451","type":"Chemical","text":["sodium"],"offsets":[[11,17]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"11452","type":"Chemical","text":["ATP"],"offsets":[[22,25]],"normalized":[{"db_name":"MESH","db_id":"D000255"}]},{"id":"11453","type":"Chemical","text":["Na"],"offsets":[[53,55]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"11454","type":"Chemical","text":["K"],"offsets":[[56,57]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"11455","type":"Chemical","text":["nitric 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{"id":"11546","document_id":"10721819","passages":[{"id":"11547","type":"title","text":["Effects of long-term pretreatment with isoproterenol on bromocriptine-induced tachycardia in conscious rats."],"offsets":[[0,108]]},{"id":"11548","type":"abstract","text":["It has been shown that bromocriptine-induced tachycardia, which persisted after adrenalectomy, is (i) mediated by central dopamine D2 receptor activation and (ii) reduced by 5-day isoproterenol pretreatment, supporting therefore the hypothesis that this effect is dependent on sympathetic outflow to the heart. This study was conducted to examine whether prolonged pretreatment with isoproterenol could abolish bromocriptine-induced tachycardia in conscious rats. Isoproterenol pretreatment for 15 days caused cardiac hypertrophy without affecting baseline blood pressure and heart rate. In control rats, intravenous bromocriptine (150 microg\/kg) induced significant hypotension and tachycardia. Bromocriptine-induced hypotension was unaffected by isoproterenol pretreatment, while tachycardia was reversed to significant bradycardia, an effect that was partly reduced by i.v. domperidone (0.5 mg\/kg). Neither cardiac vagal nor sympathetic tone was altered by isoproterenol pretreatment. In isolated perfused heart preparations from isoproterenol-pretreated rats, the isoproterenol-induced maximal increase in left ventricular systolic pressure was significantly reduced, compared with saline-pretreated rats (the EC50 of the isoproterenol-induced increase in left ventricular systolic pressure was enhanced approximately 22-fold). These results show that 15-day isoproterenol pretreatment not only abolished but reversed bromocriptine-induced tachycardia to bradycardia, an effect that is mainly related to further cardiac beta-adrenoceptor desensitization rather than to impairment of autonomic regulation of the heart. They suggest that, in normal conscious rats, the central tachycardia of bromocriptine appears to predominate and to mask the bradycardia of this agonist at peripheral dopamine D2 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{"id":"11688","document_id":"10737864","passages":[{"id":"11689","type":"title","text":["A developmental analysis of clonidine's effects on cardiac rate and ultrasound production in infant rats."],"offsets":[[0,105]]},{"id":"11690","type":"abstract","text":["Under controlled conditions, infant rats emit ultrasonic vocalizations during extreme cold exposure and after administration of the alpha(2) adrenoceptor agonist, clonidine. Previous investigations have determined that, in response to clonidine, ultrasound production increases through the 2nd-week postpartum and decreases thereafter. Given that sympathetic neural dominance exhibits a similar developmental pattern, and given that clonidine induces sympathetic withdrawal and bradycardia, we hypothesized that clonidine's developmental effects on cardiac rate and ultrasound production would mirror each other. Therefore, in the present experiment, the effects of clonidine administration (0.5 mg\/kg) on cardiac rate and ultrasound production were examined in 2-, 8-, 15-, and 20-day-old rats. Age-related changes in ultrasound production corresponded with changes in cardiovascular variables, including baseline cardiac rate and clonidine-induced bradycardia. This experiment is discussed with regard to the hypothesis that ultrasound production is the acoustic by-product of a physiological maneuver that compensates for clonidine's detrimental effects on cardiovascular function."],"offsets":[[106,1290]]}],"entities":[{"id":"11691","type":"Chemical","text":["clonidine"],"offsets":[[28,37]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]},{"id":"11692","type":"Chemical","text":["clonidine"],"offsets":[[269,278]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]},{"id":"11693","type":"Chemical","text":["clonidine"],"offsets":[[341,350]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]},{"id":"11694","type":"Chemical","text":["clonidine"],"offsets":[[539,548]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]},{"id":"11695","type":"Disease","text":["bradycardia"],"offsets":[[584,595]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"11696","type":"Chemical","text":["clonidine"],"offsets":[[618,627]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]},{"id":"11697","type":"Chemical","text":["clonidine"],"offsets":[[772,781]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]},{"id":"11698","type":"Chemical","text":["clonidine"],"offsets":[[1038,1047]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]},{"id":"11699","type":"Disease","text":["bradycardia"],"offsets":[[1056,1067]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"11700","type":"Chemical","text":["clonidine"],"offsets":[[1231,1240]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]}],"events":[],"coreferences":[],"relations":[{"id":"11701","type":"CID","arg1_id":"11691","arg2_id":"11695","normalized":[]},{"id":"11702","type":"CID","arg1_id":"11691","arg2_id":"11699","normalized":[]},{"id":"11703","type":"CID","arg1_id":"11692","arg2_id":"11695","normalized":[]},{"id":"11704","type":"CID","arg1_id":"11692","arg2_id":"11699","normalized":[]},{"id":"11705","type":"CID","arg1_id":"11693","arg2_id":"11695","normalized":[]},{"id":"11706","type":"CID","arg1_id":"11693","arg2_id":"11699","normalized":[]},{"id":"11707","type":"CID","arg1_id":"11694","arg2_id":"11695","normalized":[]},{"id":"11708","type":"CID","arg1_id":"11694","arg2_id":"11699","normalized":[]},{"id":"11709","type":"CID","arg1_id":"11696","arg2_id":"11695","normalized":[]},{"id":"11710","type":"CID","arg1_id":"11696","arg2_id":"11699","normalized":[]},{"id":"11711","type":"CID","arg1_id":"11697","arg2_id":"11695","normalized":[]},{"id":"11712","type":"CID","arg1_id":"11697","arg2_id":"11699","normalized":[]},{"id":"11713","type":"CID","arg1_id":"11698","arg2_id":"11695","normalized":[]},{"id":"11714","type":"CID","arg1_id":"11698","arg2_id":"11699","normalized":[]},{"id":"11715","type":"CID","arg1_id":"11700","arg2_id":"11695","normalized":[]},{"id":"11716","type":"CID","arg1_id":"11700","arg2_id":"11699","normalized":[]}]}
{"id":"11717","document_id":"10743446","passages":[{"id":"11718","type":"title","text":["Differential effects of systemically administered ketamine and lidocaine on dynamic and static hyperalgesia induced by intradermal capsaicin in humans."],"offsets":[[0,151]]},{"id":"11719","type":"abstract","text":["We have examined the effect of systemic administration of ketamine and lidocaine on brush-evoked (dynamic) pain and punctate-evoked (static) hyperalgesia induced by capsaicin. In a randomized, double-blind, placebo-controlled, crossover study, we studied 12 volunteers in three experiments. Capsaicin 100 micrograms was injected intradermally on the volar forearm followed by an i.v. infusion of ketamine (bolus 0.1 mg kg-1 over 10 min followed by infusion of 7 micrograms kg-1 min-1), lidocaine 5 mg kg-1 or saline for 50 min. Infusion started 15 min after injection of capsaicin. The following were measured: spontaneous pain, pain evoked by punctate and brush stimuli (VAS), and areas of brush-evoked and punctate-evoked hyperalgesia. Ketamine reduced both the area of brush-evoked and punctate-evoked hyperalgesia significantly and it tended to reduce brush-evoked pain. Lidocaine reduced the area of punctate-evoked hyperalgesia significantly. It tended to reduce VAS scores of spontaneous pain but had no effect on evoked pain. The differential effects of ketamine and lidocaine on static and dynamic hyperalgesia suggest that the two types of hyperalgesia are mediated by separate mechanisms and have a distinct 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{"id":"11799","document_id":"11007689","passages":[{"id":"11800","type":"title","text":["Cyclosporine and tacrolimus-associated thrombotic microangiopathy."],"offsets":[[0,66]]},{"id":"11801","type":"abstract","text":["The development of thrombotic microangiopathy (TMA) associated with the use of cyclosporine has been well documented. Treatments have included discontinuation or reduction of cyclosporine dose with or without concurrent plasma exchange, plasma infusion, anticoagulation, and intravenous immunoglobulin G infusion. However, for recipients of organ transplantation, removing the inciting agent is not without the attendant risk of precipitating acute rejection and graft loss. The last decade has seen the emergence of tacrolimus as a potent immunosuppressive agent with mechanisms of action virtually identical to those of cyclosporine. As a result, switching to tacrolimus has been reported to be a viable therapeutic option in the setting of cyclosporine-induced TMA. With the more widespread application of tacrolimus in organ transplantation, tacrolimus-associated TMA has also been recognized. However, literature regarding the incidence of the recurrence of TMA in patients exposed sequentially to cyclosporine and tacrolimus is limited. We report a case of a living donor renal transplant recipient who developed cyclosporine-induced TMA that responded to the withdrawal of cyclosporine in conjunction with plasmapheresis and fresh frozen plasma replacement therapy. Introduction of tacrolimus as an alternative immunosuppressive agent resulted in the recurrence of TMA and the subsequent loss of the renal allograft. Patients who are switched from cyclosporine to tacrolimus or vice versa should be closely monitored for the signs and symptoms of recurrent TMA."],"offsets":[[67,1635]]}],"entities":[{"id":"11802","type":"Chemical","text":["Cyclosporine"],"offsets":[[0,12]],"normalized":[{"db_name":"MESH","db_id":"D016572"}]},{"id":"11803","type":"Chemical","text":["tacrolimus"],"offsets":[[17,27]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"11804","type":"Disease","text":["thrombotic microangiopathy"],"offsets":[[39,65]],"normalized":[{"db_name":"MESH","db_id":"D057049"}]},{"id":"11805","type":"Disease","text":["thrombotic 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During these two episodes, his blood pressure diminished but no severe hypotension was noted. Ultimately, an arteriography showed a 70-80% renal artery stenosis. In this patient, renal artery stenosis combined with heart failure and diuretic therapy certainly resulted in a strong activation of the renin-angiotensin system (RAS). Under such conditions, angiotensin II receptor blockade by losartan probably induced a critical fall in glomerular filtration pressure. This case report highlights the fact that the angiotensin II receptor antagonist losartan can cause serious unexpected complications in patients with renovascular disease and should be used with extreme caution in this setting."],"offsets":[[97,1465]]}],"entities":[{"id":"11984","type":"Disease","text":["anuria"],"offsets":[[19,25]],"normalized":[{"db_name":"MESH","db_id":"D001002"}]},{"id":"11985","type":"Chemical","text":["losartan"],"offsets":[[36,44]],"normalized":[{"db_name":"MESH","db_id":"D019808"}]},{"id":"11986","type":"Disease","text":["hypertensive"],"offsets":[[133,145]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"11987","type":"Disease","text":["chronic renal 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{"id":"12038","document_id":"11334364","passages":[{"id":"12039","type":"title","text":["In vivo protection of dna damage associated apoptotic and necrotic cell deaths during acetaminophen-induced nephrotoxicity, amiodarone-induced lung toxicity and doxorubicin-induced cardiotoxicity by a novel IH636 grape seed proanthocyanidin extract."],"offsets":[[0,249]]},{"id":"12040","type":"abstract","text":["Grape seed extract, primarily a mixture of proanthocyanidins, has been shown to modulate a wide-range of biological, pharmacological and toxicological effects which are mainly cytoprotective. This study assessed the ability of IH636 grape seed proanthocyanidin extract (GSPE) to prevent acetaminophen (AAP)-induced nephrotoxicity, amiodarone (AMI)-induced lung toxicity, and doxorubicin (DOX)-induced cardiotoxicity in mice. Experimental design consisted of four groups: control (vehicle alone), GSPE alone, drug alone and GSPE+drug. For the cytoprotection study, animals were orally gavaged 100 mg\/Kg GSPE for 7-10 days followed by i.p. injections of organ specific three drugs (AAP: 500 mg\/Kg for 24 h; AMI: 50 mg\/Kg\/day for four days; DOX: 20 mg\/Kg for 48 h). Parameters of study included analysis of serum chemistry (ALT, BUN and CPK), and orderly fragmentation of genomic DNA (both endonuclease-dependent and independent) in addition to microscopic evaluation of damage and\/or protection in corresponding PAS stained tissues. Results indicate that GSPE preexposure prior to AAP, AMI and DOX, provided near complete protection in terms of serum chemistry changes (ALT, BUN and CPK), and significantly reduced DNA fragmentation. Histopathological examination of kidney, heart and lung sections revealed moderate to massive tissue damage with a variety of morphological aberrations by all the three drugs in the absence of GSPE preexposure than in its presence. GSPE+drug exposed tissues exhibited minor residual damage or near total recovery. Additionally, histopathological alterations mirrored both serum chemistry changes and the pattern of DNA fragmentation. Interestingly, all the drugs, such as, AAP, AMI and DOX induced apoptotic death in addition to necrosis in the respective organs which was very effectively blocked by GSPE. Since AAP, AMI and DOX undergo biotransformation and are known to produce damaging radicals in vivo, the protection by GSPE may be linked to both inhibition of metabolism and\/or detoxification of cytotoxic radicals. In addition, its' presumed contribution to DNA repair may be another important attribute, which played a role in the chemoprevention process. Additionally, this may have been the first report on AMI-induced apoptotic death in the lung tissue. Taken together, these events undoubtedly establish GSPE's abundant bioavailability, and the power to defend multiple target organs from toxic assaults induced by structurally diverse and functionally different entities in vivo."],"offsets":[[250,2775]]}],"entities":[{"id":"12041","type":"Disease","text":["necrotic"],"offsets":[[58,66]],"normalized":[{"db_name":"MESH","db_id":"D009336"}]},{"id":"12042","type":"Chemical","text":["acetaminophen"],"offsets":[[86,99]],"normalized":[{"db_name":"MESH","db_id":"D000082"}]},{"id":"12043","type":"Disease","text":["nephrotoxicity"],"offsets":[[108,122]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"12044","type":"Chemical","text":["amiodarone"],"offsets":[[124,134]],"normalized":[{"db_name":"MESH","db_id":"D000638"}]},{"id":"12045","type":"Disease","text":["lung 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{"id":"12174","document_id":"11642480","passages":[{"id":"12175","type":"title","text":["Palpebral twitching in a depressed adolescent on citalopram."],"offsets":[[0,60]]},{"id":"12176","type":"abstract","text":["Current estimates suggest that between 0.4% and 8.3% of children and adolescents are affected by major depression. We report a favorable response to treatment with citalopram by a 15-year-old boy with major depression who exhibited palpebral twitching during his first 2 weeks of treatment. This may have been a side effect of citalopram as it remitted with redistribution of doses."],"offsets":[[61,443]]}],"entities":[{"id":"12177","type":"Disease","text":["Palpebral twitching"],"offsets":[[0,19]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"12178","type":"Disease","text":["depressed"],"offsets":[[25,34]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"12179","type":"Chemical","text":["citalopram"],"offsets":[[49,59]],"normalized":[{"db_name":"MESH","db_id":"D015283"}]},{"id":"12180","type":"Disease","text":["major depression"],"offsets":[[158,174]],"normalized":[{"db_name":"MESH","db_id":"D003865"}]},{"id":"12181","type":"Chemical","text":["citalopram"],"offsets":[[225,235]],"normalized":[{"db_name":"MESH","db_id":"D015283"}]},{"id":"12182","type":"Disease","text":["major depression"],"offsets":[[262,278]],"normalized":[{"db_name":"MESH","db_id":"D003865"}]},{"id":"12183","type":"Disease","text":["palpebral twitching"],"offsets":[[293,312]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"12184","type":"Chemical","text":["citalopram"],"offsets":[[388,398]],"normalized":[{"db_name":"MESH","db_id":"D015283"}]}],"events":[],"coreferences":[],"relations":[{"id":"12185","type":"CID","arg1_id":"12179","arg2_id":"12177","normalized":[]},{"id":"12186","type":"CID","arg1_id":"12179","arg2_id":"12183","normalized":[]},{"id":"12187","type":"CID","arg1_id":"12181","arg2_id":"12177","normalized":[]},{"id":"12188","type":"CID","arg1_id":"12181","arg2_id":"12183","normalized":[]},{"id":"12189","type":"CID","arg1_id":"12184","arg2_id":"12177","normalized":[]},{"id":"12190","type":"CID","arg1_id":"12184","arg2_id":"12183","normalized":[]}]}
{"id":"12191","document_id":"12063090","passages":[{"id":"12192","type":"title","text":["Metamizol potentiates morphine antinociception but not constipation after chronic treatment."],"offsets":[[0,92]]},{"id":"12193","type":"abstract","text":["This work evaluates the antinociceptive and constipating effects of the combination of 3.2 mg\/kg s.c. morphine with 177.8 mg\/kg s.c. metamizol in acutely and chronically treated (once a day for 12 days) rats. On the 13th day, antinociceptive effects were assessed using a model of inflammatory nociception, pain-induced functional impairment model, and the charcoal meal test was used to evaluate the intestinal transit. Simultaneous administration of morphine with metamizol resulted in a markedly antinociceptive potentiation and an increasing of the duration of action after a single (298+\/-7 vs. 139+\/-36 units area (ua); P<0.001) and repeated administration (280+\/-17 vs. 131+\/-22 ua; P<0.001). Antinociceptive effect of morphine was reduced in chronically treated rats (39+\/-10 vs. 18+\/-5 au) while the combination-induced antinociception was remained similar as an acute treatment (298+\/-7 vs. 280+\/-17 au). Acute antinociceptive effects of the combination were partially prevented by 3.2 mg\/kg naloxone s.c. (P<0.05), suggesting the partial involvement of the opioidergic system in the synergism observed. In independent groups, morphine inhibited the intestinal transit in 48+\/-4% and 38+\/-4% after acute and chronic treatment, respectively, suggesting that tolerance did not develop to the constipating effects. The combination inhibited intestinal transit similar to that produced by morphine regardless of the time of treatment, suggesting that metamizol did not potentiate morphine-induced constipation. These findings show a significant interaction between morphine and metamizol in chronically treated rats, suggesting that this combination could be useful for the treatment of chronic pain."],"offsets":[[93,1799]]}],"entities":[{"id":"12194","type":"Chemical","text":["Metamizol"],"offsets":[[0,9]],"normalized":[{"db_name":"MESH","db_id":"D004177"}]},{"id":"12195","type":"Chemical","text":["morphine"],"offsets":[[22,30]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"12196","type":"Disease","text":["constipation"],"offsets":[[55,67]],"normalized":[{"db_name":"MESH","db_id":"D003248"}]},{"id":"12197","type":"Disease","text":["constipating"],"offsets":[[137,149]],"normalized":[{"db_name":"MESH","db_id":"D003248"}]},{"id":"12198","type":"Chemical","text":["morphine"],"offsets":[[195,203]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"12199","type":"Chemical","text":["metamizol"],"offsets":[[226,235]],"normalized":[{"db_name":"MESH","db_id":"D004177"}]},{"id":"12200","type":"Disease","text":["pain"],"offsets":[[400,404]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"12201","type":"Chemical","text":["charcoal"],"offsets":[[450,458]],"normalized":[{"db_name":"MESH","db_id":"D002606"}]},{"id":"12202","type":"Chemical","text":["morphine"],"offsets":[[545,553]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"12203","type":"Chemical","text":["metamizol"],"offsets":[[559,568]],"normalized":[{"db_name":"MESH","db_id":"D004177"}]},{"id":"12204","type":"Chemical","text":["morphine"],"offsets":[[819,827]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"12205","type":"Chemical","text":["naloxone"],"offsets":[[1095,1103]],"normalized":[{"db_name":"MESH","db_id":"D009270"}]},{"id":"12206","type":"Chemical","text":["morphine"],"offsets":[[1230,1238]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"12207","type":"Disease","text":["constipating"],"offsets":[[1393,1405]],"normalized":[{"db_name":"MESH","db_id":"D003248"}]},{"id":"12208","type":"Chemical","text":["morphine"],"offsets":[[1488,1496]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"12209","type":"Chemical","text":["metamizol"],"offsets":[[1550,1559]],"normalized":[{"db_name":"MESH","db_id":"D004177"}]},{"id":"12210","type":"Chemical","text":["morphine"],"offsets":[[1579,1587]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"12211","type":"Disease","text":["constipation"],"offsets":[[1596,1608]],"normalized":[{"db_name":"MESH","db_id":"D003248"}]},{"id":"12212","type":"Chemical","text":["morphine"],"offsets":[[1664,1672]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"12213","type":"Chemical","text":["metamizol"],"offsets":[[1677,1686]],"normalized":[{"db_name":"MESH","db_id":"D004177"}]},{"id":"12214","type":"Disease","text":["chronic pain"],"offsets":[[1786,1798]],"normalized":[{"db_name":"MESH","db_id":"D059350"}]}],"events":[],"coreferences":[],"relations":[{"id":"12215","type":"CID","arg1_id":"12195","arg2_id":"12196","normalized":[]},{"id":"12216","type":"CID","arg1_id":"12195","arg2_id":"12197","normalized":[]},{"id":"12217","type":"CID","arg1_id":"12195","arg2_id":"12207","normalized":[]},{"id":"12218","type":"CID","arg1_id":"12195","arg2_id":"12211","normalized":[]},{"id":"12219","type":"CID","arg1_id":"12198","arg2_id":"12196","normalized":[]},{"id":"12220","type":"CID","arg1_id":"12198","arg2_id":"12197","normalized":[]},{"id":"12221","type":"CID","arg1_id":"12198","arg2_id":"12207","normalized":[]},{"id":"12222","type":"CID","arg1_id":"12198","arg2_id":"12211","normalized":[]},{"id":"12223","type":"CID","arg1_id":"12202","arg2_id":"12196","normalized":[]},{"id":"12224","type":"CID","arg1_id":"12202","arg2_id":"12197","normalized":[]},{"id":"12225","type":"CID","arg1_id":"12202","arg2_id":"12207","normalized":[]},{"id":"12226","type":"CID","arg1_id":"12202","arg2_id":"12211","normalized":[]},{"id":"12227","type":"CID","arg1_id":"12204","arg2_id":"12196","normalized":[]},{"id":"12228","type":"CID","arg1_id":"12204","arg2_id":"12197","normalized":[]},{"id":"12229","type":"CID","arg1_id":"12204","arg2_id":"12207","normalized":[]},{"id":"12230","type":"CID","arg1_id":"12204","arg2_id":"12211","normalized":[]},{"id":"12231","type":"CID","arg1_id":"12206","arg2_id":"12196","normalized":[]},{"id":"12232","type":"CID","arg1_id":"12206","arg2_id":"12197","normalized":[]},{"id":"12233","type":"CID","arg1_id":"12206","arg2_id":"12207","normalized":[]},{"id":"12234","type":"CID","arg1_id":"12206","arg2_id":"12211","normalized":[]},{"id":"12235","type":"CID","arg1_id":"12208","arg2_id":"12196","normalized":[]},{"id":"12236","type":"CID","arg1_id":"12208","arg2_id":"12197","normalized":[]},{"id":"12237","type":"CID","arg1_id":"12208","arg2_id":"12207","normalized":[]},{"id":"12238","type":"CID","arg1_id":"12208","arg2_id":"12211","normalized":[]},{"id":"12239","type":"CID","arg1_id":"12210","arg2_id":"12196","normalized":[]},{"id":"12240","type":"CID","arg1_id":"12210","arg2_id":"12197","normalized":[]},{"id":"12241","type":"CID","arg1_id":"12210","arg2_id":"12207","normalized":[]},{"id":"12242","type":"CID","arg1_id":"12210","arg2_id":"12211","normalized":[]},{"id":"12243","type":"CID","arg1_id":"12212","arg2_id":"12196","normalized":[]},{"id":"12244","type":"CID","arg1_id":"12212","arg2_id":"12197","normalized":[]},{"id":"12245","type":"CID","arg1_id":"12212","arg2_id":"12207","normalized":[]},{"id":"12246","type":"CID","arg1_id":"12212","arg2_id":"12211","normalized":[]}]}
{"id":"12247","document_id":"12084448","passages":[{"id":"12248","type":"title","text":["Ifosfamide encephalopathy presenting with asterixis."],"offsets":[[0,52]]},{"id":"12249","type":"abstract","text":["CNS toxic effects of the antineoplastic agent ifosfamide (IFX) are frequent and include a variety of neurological symptoms that can limit drug use. We report a case of a 51-year-old man who developed severe, disabling negative myoclonus of the upper and lower extremities after the infusion of ifosfamide for plasmacytoma. He was awake, revealed no changes of mental status and at rest there were no further motor symptoms. Cranial magnetic resonance imaging and extensive laboratory studies failed to reveal structural lesions of the brain and metabolic abnormalities. An electroencephalogram showed continuous, generalized irregular slowing with admixed periodic triphasic waves indicating symptomatic encephalopathy. The administration of ifosfamide was discontinued and within 12 h the asterixis resolved completely. In the patient described, the presence of asterixis during infusion of ifosfamide, normal laboratory findings and imaging studies and the resolution of symptoms following the discontinuation of the drug suggest that negative myoclonus is associated with the use of IFX."],"offsets":[[53,1143]]}],"entities":[{"id":"12250","type":"Chemical","text":["Ifosfamide"],"offsets":[[0,10]],"normalized":[{"db_name":"MESH","db_id":"D007069"}]},{"id":"12251","type":"Disease","text":["encephalopathy"],"offsets":[[11,25]],"normalized":[{"db_name":"MESH","db_id":"D001927"}]},{"id":"12252","type":"Disease","text":["asterixis"],"offsets":[[42,51]],"normalized":[{"db_name":"MESH","db_id":"D020820"}]},{"id":"12253","type":"Chemical","text":["ifosfamide"],"offsets":[[99,109]],"normalized":[{"db_name":"MESH","db_id":"D007069"}]},{"id":"12254","type":"Chemical","text":["IFX"],"offsets":[[111,114]],"normalized":[{"db_name":"MESH","db_id":"D007069"}]},{"id":"12255","type":"Disease","text":["myoclonus"],"offsets":[[280,289]],"normalized":[{"db_name":"MESH","db_id":"D009207"}]},{"id":"12256","type":"Chemical","text":["ifosfamide"],"offsets":[[347,357]],"normalized":[{"db_name":"MESH","db_id":"D007069"}]},{"id":"12257","type":"Disease","text":["plasmacytoma"],"offsets":[[362,374]],"normalized":[{"db_name":"MESH","db_id":"D010954"}]},{"id":"12258","type":"Disease","text":["structural lesions of the brain"],"offsets":[[562,593]],"normalized":[{"db_name":"MESH","db_id":"D001927"}]},{"id":"12259","type":"Disease","text":["metabolic abnormalities"],"offsets":[[598,621]],"normalized":[{"db_name":"MESH","db_id":"D008659"}]},{"id":"12260","type":"Disease","text":["encephalopathy"],"offsets":[[757,771]],"normalized":[{"db_name":"MESH","db_id":"D001927"}]},{"id":"12261","type":"Chemical","text":["ifosfamide"],"offsets":[[795,805]],"normalized":[{"db_name":"MESH","db_id":"D007069"}]},{"id":"12262","type":"Disease","text":["asterixis"],"offsets":[[843,852]],"normalized":[{"db_name":"MESH","db_id":"D020820"}]},{"id":"12263","type":"Disease","text":["asterixis"],"offsets":[[916,925]],"normalized":[{"db_name":"MESH","db_id":"D020820"}]},{"id":"12264","type":"Chemical","text":["ifosfamide"],"offsets":[[945,955]],"normalized":[{"db_name":"MESH","db_id":"D007069"}]},{"id":"12265","type":"Disease","text":["myoclonus"],"offsets":[[1099,1108]],"normalized":[{"db_name":"MESH","db_id":"D009207"}]},{"id":"12266","type":"Chemical","text":["IFX"],"offsets":[[1139,1142]],"normalized":[{"db_name":"MESH","db_id":"D007069"}]}],"events":[],"coreferences":[],"relations":[{"id":"12267","type":"CID","arg1_id":"12250","arg2_id":"12255","normalized":[]},{"id":"12268","type":"CID","arg1_id":"12250","arg2_id":"12265","normalized":[]},{"id":"12269","type":"CID","arg1_id":"12253","arg2_id":"12255","normalized":[]},{"id":"12270","type":"CID","arg1_id":"12253","arg2_id":"12265","normalized":[]},{"id":"12271","type":"CID","arg1_id":"12254","arg2_id":"12255","normalized":[]},{"id":"12272","type":"CID","arg1_id":"12254","arg2_id":"12265","normalized":[]},{"id":"12273","type":"CID","arg1_id":"12256","arg2_id":"12255","normalized":[]},{"id":"12274","type":"CID","arg1_id":"12256","arg2_id":"12265","normalized":[]},{"id":"12275","type":"CID","arg1_id":"12261","arg2_id":"12255","normalized":[]},{"id":"12276","type":"CID","arg1_id":"12261","arg2_id":"12265","normalized":[]},{"id":"12277","type":"CID","arg1_id":"12264","arg2_id":"12255","normalized":[]},{"id":"12278","type":"CID","arg1_id":"12264","arg2_id":"12265","normalized":[]},{"id":"12279","type":"CID","arg1_id":"12266","arg2_id":"12255","normalized":[]},{"id":"12280","type":"CID","arg1_id":"12266","arg2_id":"12265","normalized":[]},{"id":"12281","type":"CID","arg1_id":"12250","arg2_id":"12251","normalized":[]},{"id":"12282","type":"CID","arg1_id":"12250","arg2_id":"12258","normalized":[]},{"id":"12283","type":"CID","arg1_id":"12250","arg2_id":"12260","normalized":[]},{"id":"12284","type":"CID","arg1_id":"12253","arg2_id":"12251","normalized":[]},{"id":"12285","type":"CID","arg1_id":"12253","arg2_id":"12258","normalized":[]},{"id":"12286","type":"CID","arg1_id":"12253","arg2_id":"12260","normalized":[]},{"id":"12287","type":"CID","arg1_id":"12254","arg2_id":"12251","normalized":[]},{"id":"12288","type":"CID","arg1_id":"12254","arg2_id":"12258","normalized":[]},{"id":"12289","type":"CID","arg1_id":"12254","arg2_id":"12260","normalized":[]},{"id":"12290","type":"CID","arg1_id":"12256","arg2_id":"12251","normalized":[]},{"id":"12291","type":"CID","arg1_id":"12256","arg2_id":"12258","normalized":[]},{"id":"12292","type":"CID","arg1_id":"12256","arg2_id":"12260","normalized":[]},{"id":"12293","type":"CID","arg1_id":"12261","arg2_id":"12251","normalized":[]},{"id":"12294","type":"CID","arg1_id":"12261","arg2_id":"12258","normalized":[]},{"id":"12295","type":"CID","arg1_id":"12261","arg2_id":"12260","normalized":[]},{"id":"12296","type":"CID","arg1_id":"12264","arg2_id":"12251","normalized":[]},{"id":"12297","type":"CID","arg1_id":"12264","arg2_id":"12258","normalized":[]},{"id":"12298","type":"CID","arg1_id":"12264","arg2_id":"12260","normalized":[]},{"id":"12299","type":"CID","arg1_id":"12266","arg2_id":"12251","normalized":[]},{"id":"12300","type":"CID","arg1_id":"12266","arg2_id":"12258","normalized":[]},{"id":"12301","type":"CID","arg1_id":"12266","arg2_id":"12260","normalized":[]}]}
{"id":"12302","document_id":"12684739","passages":[{"id":"12303","type":"title","text":["Sub-chronic low dose gamma-vinyl GABA (vigabatrin) inhibits cocaine-induced increases in nucleus accumbens dopamine."],"offsets":[[0,116]]},{"id":"12304","type":"abstract","text":["RATIONALE: gamma-Vinyl GABA (GVG) irreversibly inhibits GABA-transaminase. This non-receptor mediated inhibition requires de novo synthesis for restoration of functional GABA catabolism. OBJECTIVES: Given its preclinical success for treating substance abuse and the increased risk of visual field defects (VFD) associated with cumulative lifetime exposure, we explored the effects of sub-chronic low dose GVG on cocaine-induced increases in nucleus accumbens (NAcc) dopamine (DA). METHODS: Using in vivo microdialysis, we compared acute exposure (450 mg\/kg) to an identical sub-chronic exposure (150 mg\/kg per day for 3 days), followed by 1- or 3-day washout. Finally, we examined the low dose of 150 mg\/kg (50 mg\/kg per day) using a similar washout period. RESULTS: Sub-chronic GVG exposure inhibited the effect of cocaine for 3 days, which exceeded in magnitude and duration the identical acute dose. CONCLUSIONS: Sub-chronic low dose GVG potentiates and extends the inhibition of cocaine-induced increases in dopamine, effectively reducing cumulative exposures and the risk for VFDS."],"offsets":[[117,1203]]}],"entities":[{"id":"12305","type":"Chemical","text":["gamma-vinyl GABA"],"offsets":[[21,37]],"normalized":[{"db_name":"MESH","db_id":"D020888"}]},{"id":"12306","type":"Chemical","text":["vigabatrin"],"offsets":[[39,49]],"normalized":[{"db_name":"MESH","db_id":"D020888"}]},{"id":"12307","type":"Chemical","text":["cocaine"],"offsets":[[60,67]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"12308","type":"Chemical","text":["dopamine"],"offsets":[[107,115]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"12309","type":"Chemical","text":["gamma-Vinyl GABA"],"offsets":[[128,144]],"normalized":[{"db_name":"MESH","db_id":"D020888"}]},{"id":"12310","type":"Chemical","text":["GVG"],"offsets":[[146,149]],"normalized":[{"db_name":"MESH","db_id":"D020888"}]},{"id":"12311","type":"Chemical","text":["GABA"],"offsets":[[173,177]],"normalized":[{"db_name":"MESH","db_id":"D005680"}]},{"id":"12312","type":"Chemical","text":["GABA"],"offsets":[[287,291]],"normalized":[{"db_name":"MESH","db_id":"D005680"}]},{"id":"12313","type":"Disease","text":["substance abuse"],"offsets":[[359,374]],"normalized":[{"db_name":"MESH","db_id":"D019966"}]},{"id":"12314","type":"Disease","text":["visual field defects"],"offsets":[[401,421]],"normalized":[{"db_name":"MESH","db_id":"D005128"}]},{"id":"12315","type":"Disease","text":["VFD"],"offsets":[[423,426]],"normalized":[{"db_name":"MESH","db_id":"D005128"}]},{"id":"12316","type":"Chemical","text":["GVG"],"offsets":[[522,525]],"normalized":[{"db_name":"MESH","db_id":"D020888"}]},{"id":"12317","type":"Chemical","text":["cocaine"],"offsets":[[529,536]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"12318","type":"Chemical","text":["dopamine"],"offsets":[[583,591]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"12319","type":"Chemical","text":["DA"],"offsets":[[593,595]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"12320","type":"Chemical","text":["GVG"],"offsets":[[896,899]],"normalized":[{"db_name":"MESH","db_id":"D020888"}]},{"id":"12321","type":"Chemical","text":["cocaine"],"offsets":[[933,940]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"12322","type":"Chemical","text":["GVG"],"offsets":[[1054,1057]],"normalized":[{"db_name":"MESH","db_id":"D020888"}]},{"id":"12323","type":"Chemical","text":["cocaine"],"offsets":[[1100,1107]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"12324","type":"Chemical","text":["dopamine"],"offsets":[[1129,1137]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]}],"events":[],"coreferences":[],"relations":[{"id":"12325","type":"CID","arg1_id":"12305","arg2_id":"12314","normalized":[]},{"id":"12326","type":"CID","arg1_id":"12305","arg2_id":"12315","normalized":[]},{"id":"12327","type":"CID","arg1_id":"12306","arg2_id":"12314","normalized":[]},{"id":"12328","type":"CID","arg1_id":"12306","arg2_id":"12315","normalized":[]},{"id":"12329","type":"CID","arg1_id":"12309","arg2_id":"12314","normalized":[]},{"id":"12330","type":"CID","arg1_id":"12309","arg2_id":"12315","normalized":[]},{"id":"12331","type":"CID","arg1_id":"12310","arg2_id":"12314","normalized":[]},{"id":"12332","type":"CID","arg1_id":"12310","arg2_id":"12315","normalized":[]},{"id":"12333","type":"CID","arg1_id":"12316","arg2_id":"12314","normalized":[]},{"id":"12334","type":"CID","arg1_id":"12316","arg2_id":"12315","normalized":[]},{"id":"12335","type":"CID","arg1_id":"12320","arg2_id":"12314","normalized":[]},{"id":"12336","type":"CID","arg1_id":"12320","arg2_id":"12315","normalized":[]},{"id":"12337","type":"CID","arg1_id":"12322","arg2_id":"12314","normalized":[]},{"id":"12338","type":"CID","arg1_id":"12322","arg2_id":"12315","normalized":[]}]}
{"id":"12339","document_id":"12716030","passages":[{"id":"12340","type":"title","text":["Amount of bleeding and hematoma size in the collagenase-induced intracerebral hemorrhage rat model."],"offsets":[[0,99]]},{"id":"12341","type":"abstract","text":["The aggravated risk on intracerebral hemorrhage (ICH) with drugs used for stroke patients should be estimated carefully. We therefore established sensitive quantification methods and provided a rat ICH model for detection of ICH deterioration. In ICH intrastriatally induced by 0.014-unit, 0.070-unit, and 0.350-unit collagenase, the amount of bleeding was measured using a hemoglobin assay developed in the present study and was compared with the morphologically determined hematoma volume. The blood amounts and hematoma volumes were significantly correlated, and the hematoma induced by 0.014-unit collagenase was adequate to detect ICH deterioration. In ICH induction using 0.014-unit collagenase, heparin enhanced the hematoma volume 3.4-fold over that seen in control ICH animals and the bleeding 7.6-fold. Data suggest that this sensitive hemoglobin assay is useful for ICH detection, and that a model with a small ICH induced with a low-dose collagenase should be used for evaluation of drugs that may affect ICH."],"offsets":[[100,1121]]}],"entities":[{"id":"12342","type":"Disease","text":["bleeding"],"offsets":[[10,18]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"12343","type":"Disease","text":["hematoma"],"offsets":[[23,31]],"normalized":[{"db_name":"MESH","db_id":"D006406"}]},{"id":"12344","type":"Disease","text":["intracerebral hemorrhage"],"offsets":[[64,88]],"normalized":[{"db_name":"MESH","db_id":"D002543"}]},{"id":"12345","type":"Disease","text":["intracerebral hemorrhage"],"offsets":[[123,147]],"normalized":[{"db_name":"MESH","db_id":"D002543"}]},{"id":"12346","type":"Disease","text":["ICH"],"offsets":[[149,152]],"normalized":[{"db_name":"MESH","db_id":"D002543"}]},{"id":"12347","type":"Disease","text":["stroke"],"offsets":[[174,180]],"normalized":[{"db_name":"MESH","db_id":"D020521"}]},{"id":"12348","type":"Disease","text":["ICH"],"offsets":[[298,301]],"normalized":[{"db_name":"MESH","db_id":"D002543"}]},{"id":"12349","type":"Disease","text":["ICH"],"offsets":[[325,328]],"normalized":[{"db_name":"MESH","db_id":"D002543"}]},{"id":"12350","type":"Disease","text":["ICH"],"offsets":[[347,350]],"normalized":[{"db_name":"MESH","db_id":"D002543"}]},{"id":"12351","type":"Disease","text":["bleeding"],"offsets":[[444,452]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"12352","type":"Disease","text":["hematoma"],"offsets":[[575,583]],"normalized":[{"db_name":"MESH","db_id":"D006406"}]},{"id":"12353","type":"Disease","text":["hematoma"],"offsets":[[614,622]],"normalized":[{"db_name":"MESH","db_id":"D006406"}]},{"id":"12354","type":"Disease","text":["hematoma"],"offsets":[[670,678]],"normalized":[{"db_name":"MESH","db_id":"D006406"}]},{"id":"12355","type":"Disease","text":["ICH"],"offsets":[[736,739]],"normalized":[{"db_name":"MESH","db_id":"D002543"}]},{"id":"12356","type":"Disease","text":["ICH"],"offsets":[[758,761]],"normalized":[{"db_name":"MESH","db_id":"D002543"}]},{"id":"12357","type":"Chemical","text":["heparin"],"offsets":[[802,809]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"12358","type":"Disease","text":["hematoma"],"offsets":[[823,831]],"normalized":[{"db_name":"MESH","db_id":"D006406"}]},{"id":"12359","type":"Disease","text":["ICH"],"offsets":[[874,877]],"normalized":[{"db_name":"MESH","db_id":"D002543"}]},{"id":"12360","type":"Disease","text":["bleeding"],"offsets":[[894,902]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"12361","type":"Disease","text":["ICH"],"offsets":[[977,980]],"normalized":[{"db_name":"MESH","db_id":"D002543"}]},{"id":"12362","type":"Disease","text":["ICH"],"offsets":[[1022,1025]],"normalized":[{"db_name":"MESH","db_id":"D002543"}]},{"id":"12363","type":"Disease","text":["ICH"],"offsets":[[1117,1120]],"normalized":[{"db_name":"MESH","db_id":"D002543"}]}],"events":[],"coreferences":[],"relations":[{"id":"12364","type":"CID","arg1_id":"12357","arg2_id":"12343","normalized":[]},{"id":"12365","type":"CID","arg1_id":"12357","arg2_id":"12352","normalized":[]},{"id":"12366","type":"CID","arg1_id":"12357","arg2_id":"12353","normalized":[]},{"id":"12367","type":"CID","arg1_id":"12357","arg2_id":"12354","normalized":[]},{"id":"12368","type":"CID","arg1_id":"12357","arg2_id":"12358","normalized":[]}]}
{"id":"12369","document_id":"12757899","passages":[{"id":"12370","type":"title","text":["Estradiol reduces seizure-induced hippocampal injury in ovariectomized female but not in male rats."],"offsets":[[0,99]]},{"id":"12371","type":"abstract","text":["Estrogens protect ovariectomized rats from hippocampal injury induced by kainic acid-induced status epilepticus (SE). We compared the effects of 17beta-estradiol in adult male and ovariectomized female rats subjected to lithium-pilocarpine-induced SE. Rats received subcutaneous injections of 17beta-estradiol (2 microg\/rat) or oil once daily for four consecutive days. SE was induced 20 h following the second injection and terminated 3 h later. The extent of silver-stained CA3 and CA1 hippocampal neurons was evaluated 2 days after SE. 17beta-Estradiol did not alter the onset of first clonus in ovariectomized rats but accelerated it in males. 17beta-Estradiol reduced the argyrophilic neurons in the CA1 and CA3-C sectors of ovariectomized rats. In males, estradiol increased the total damage score. These findings suggest that the effects of estradiol on seizure threshold and damage may be altered by sex-related differences in the hormonal environment."],"offsets":[[100,1060]]}],"entities":[{"id":"12372","type":"Chemical","text":["Estradiol"],"offsets":[[0,9]],"normalized":[{"db_name":"MESH","db_id":"D004958"}]},{"id":"12373","type":"Disease","text":["seizure"],"offsets":[[18,25]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"12374","type":"Disease","text":["hippocampal injury"],"offsets":[[34,52]],"normalized":[{"db_name":"MESH","db_id":"D001930"}]},{"id":"12375","type":"Disease","text":["hippocampal injury"],"offsets":[[143,161]],"normalized":[{"db_name":"MESH","db_id":"D001930"}]},{"id":"12376","type":"Chemical","text":["kainic acid"],"offsets":[[173,184]],"normalized":[{"db_name":"MESH","db_id":"D007608"}]},{"id":"12377","type":"Disease","text":["status epilepticus"],"offsets":[[193,211]],"normalized":[{"db_name":"MESH","db_id":"D013226"}]},{"id":"12378","type":"Disease","text":["SE"],"offsets":[[213,215]],"normalized":[{"db_name":"MESH","db_id":"D013226"}]},{"id":"12379","type":"Chemical","text":["17beta-estradiol"],"offsets":[[245,261]],"normalized":[{"db_name":"MESH","db_id":"D004958"}]},{"id":"12380","type":"Chemical","text":["lithium"],"offsets":[[320,327]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"12381","type":"Chemical","text":["pilocarpine"],"offsets":[[328,339]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"12382","type":"Disease","text":["SE"],"offsets":[[348,350]],"normalized":[{"db_name":"MESH","db_id":"D013226"}]},{"id":"12383","type":"Chemical","text":["17beta-estradiol"],"offsets":[[393,409]],"normalized":[{"db_name":"MESH","db_id":"D004958"}]},{"id":"12384","type":"Disease","text":["SE"],"offsets":[[470,472]],"normalized":[{"db_name":"MESH","db_id":"D013226"}]},{"id":"12385","type":"Chemical","text":["silver"],"offsets":[[561,567]],"normalized":[{"db_name":"MESH","db_id":"D012834"}]},{"id":"12386","type":"Disease","text":["SE"],"offsets":[[635,637]],"normalized":[{"db_name":"MESH","db_id":"D013226"}]},{"id":"12387","type":"Chemical","text":["17beta-Estradiol"],"offsets":[[639,655]],"normalized":[{"db_name":"MESH","db_id":"D004958"}]},{"id":"12388","type":"Chemical","text":["17beta-Estradiol"],"offsets":[[748,764]],"normalized":[{"db_name":"MESH","db_id":"D004958"}]},{"id":"12389","type":"Chemical","text":["estradiol"],"offsets":[[861,870]],"normalized":[{"db_name":"MESH","db_id":"D004958"}]},{"id":"12390","type":"Chemical","text":["estradiol"],"offsets":[[948,957]],"normalized":[{"db_name":"MESH","db_id":"D004958"}]},{"id":"12391","type":"Disease","text":["seizure"],"offsets":[[961,968]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]}],"events":[],"coreferences":[],"relations":[{"id":"12392","type":"CID","arg1_id":"12380","arg2_id":"12377","normalized":[]},{"id":"12393","type":"CID","arg1_id":"12380","arg2_id":"12378","normalized":[]},{"id":"12394","type":"CID","arg1_id":"12380","arg2_id":"12382","normalized":[]},{"id":"12395","type":"CID","arg1_id":"12380","arg2_id":"12384","normalized":[]},{"id":"12396","type":"CID","arg1_id":"12380","arg2_id":"12386","normalized":[]},{"id":"12397","type":"CID","arg1_id":"12380","arg2_id":"12374","normalized":[]},{"id":"12398","type":"CID","arg1_id":"12380","arg2_id":"12375","normalized":[]},{"id":"12399","type":"CID","arg1_id":"12381","arg2_id":"12377","normalized":[]},{"id":"12400","type":"CID","arg1_id":"12381","arg2_id":"12378","normalized":[]},{"id":"12401","type":"CID","arg1_id":"12381","arg2_id":"12382","normalized":[]},{"id":"12402","type":"CID","arg1_id":"12381","arg2_id":"12384","normalized":[]},{"id":"12403","type":"CID","arg1_id":"12381","arg2_id":"12386","normalized":[]},{"id":"12404","type":"CID","arg1_id":"12381","arg2_id":"12374","normalized":[]},{"id":"12405","type":"CID","arg1_id":"12381","arg2_id":"12375","normalized":[]}]}
{"id":"12406","document_id":"12905102","passages":[{"id":"12407","type":"title","text":["Delirium during clozapine treatment: incidence and associated risk factors."],"offsets":[[0,75]]},{"id":"12408","type":"abstract","text":["BACKGROUND: Incidence and risk factors for delirium during clozapine treatment require further clarification. METHODS: We used computerized pharmacy records to identify all adult psychiatric inpatients treated with clozapine (1995-96), reviewed their medical records to score incidence and severity of delirium, and tested associations with potential risk factors. RESULTS: Subjects (n = 139) were 72 women and 67 men, aged 40.8 +\/- 12.1 years, hospitalized for 24.9 +\/- 23.3 days, and given clozapine, gradually increased to an average daily dose of 282 +\/- 203 mg (3.45 +\/- 2.45 mg\/kg) for 18.9 +\/- 16.4 days. Delirium was diagnosed in 14 (10.1 % incidence, or 1.48 cases\/person-years of exposure); 71.4 % of cases were moderate or severe. Associated factors were co-treatment with other centrally antimuscarinic agents, poor clinical outcome, older age, and longer hospitalization (by 17.5 days, increasing cost); sex, diagnosis or medical co-morbidity, and daily clozapine dose, which fell with age, were unrelated. CONCLUSIONS: Delirium was found in 10 % of clozapine-treated inpatients, particularly in older patients exposed to other central anticholinergics. Delirium was inconsistently recognized clinically in milder cases and was associated with increased length-of-stay and higher costs, and inferior clinical outcome."],"offsets":[[76,1406]]}],"entities":[{"id":"12409","type":"Disease","text":["Delirium"],"offsets":[[0,8]],"normalized":[{"db_name":"MESH","db_id":"D003693"}]},{"id":"12410","type":"Chemical","text":["clozapine"],"offsets":[[16,25]],"normalized":[{"db_name":"MESH","db_id":"D003024"}]},{"id":"12411","type":"Disease","text":["delirium"],"offsets":[[119,127]],"normalized":[{"db_name":"MESH","db_id":"D003693"}]},{"id":"12412","type":"Chemical","text":["clozapine"],"offsets":[[135,144]],"normalized":[{"db_name":"MESH","db_id":"D003024"}]},{"id":"12413","type":"Disease","text":["psychiatric"],"offsets":[[255,266]],"normalized":[{"db_name":"MESH","db_id":"D001523"}]},{"id":"12414","type":"Chemical","text":["clozapine"],"offsets":[[291,300]],"normalized":[{"db_name":"MESH","db_id":"D003024"}]},{"id":"12415","type":"Disease","text":["delirium"],"offsets":[[378,386]],"normalized":[{"db_name":"MESH","db_id":"D003693"}]},{"id":"12416","type":"Chemical","text":["clozapine"],"offsets":[[568,577]],"normalized":[{"db_name":"MESH","db_id":"D003024"}]},{"id":"12417","type":"Disease","text":["Delirium"],"offsets":[[688,696]],"normalized":[{"db_name":"MESH","db_id":"D003693"}]},{"id":"12418","type":"Chemical","text":["clozapine"],"offsets":[[1043,1052]],"normalized":[{"db_name":"MESH","db_id":"D003024"}]},{"id":"12419","type":"Disease","text":["Delirium"],"offsets":[[1109,1117]],"normalized":[{"db_name":"MESH","db_id":"D003693"}]},{"id":"12420","type":"Chemical","text":["clozapine"],"offsets":[[1139,1148]],"normalized":[{"db_name":"MESH","db_id":"D003024"}]},{"id":"12421","type":"Disease","text":["Delirium"],"offsets":[[1243,1251]],"normalized":[{"db_name":"MESH","db_id":"D003693"}]}],"events":[],"coreferences":[],"relations":[{"id":"12422","type":"CID","arg1_id":"12410","arg2_id":"12409","normalized":[]},{"id":"12423","type":"CID","arg1_id":"12410","arg2_id":"12411","normalized":[]},{"id":"12424","type":"CID","arg1_id":"12410","arg2_id":"12415","normalized":[]},{"id":"12425","type":"CID","arg1_id":"12410","arg2_id":"12417","normalized":[]},{"id":"12426","type":"CID","arg1_id":"12410","arg2_id":"12419","normalized":[]},{"id":"12427","type":"CID","arg1_id":"12410","arg2_id":"12421","normalized":[]},{"id":"12428","type":"CID","arg1_id":"12412","arg2_id":"12409","normalized":[]},{"id":"12429","type":"CID","arg1_id":"12412","arg2_id":"12411","normalized":[]},{"id":"12430","type":"CID","arg1_id":"12412","arg2_id":"12415","normalized":[]},{"id":"12431","type":"CID","arg1_id":"12412","arg2_id":"12417","normalized":[]},{"id":"12432","type":"CID","arg1_id":"12412","arg2_id":"12419","normalized":[]},{"id":"12433","type":"CID","arg1_id":"12412","arg2_id":"12421","normalized":[]},{"id":"12434","type":"CID","arg1_id":"12414","arg2_id":"12409","normalized":[]},{"id":"12435","type":"CID","arg1_id":"12414","arg2_id":"12411","normalized":[]},{"id":"12436","type":"CID","arg1_id":"12414","arg2_id":"12415","normalized":[]},{"id":"12437","type":"CID","arg1_id":"12414","arg2_id":"12417","normalized":[]},{"id":"12438","type":"CID","arg1_id":"12414","arg2_id":"12419","normalized":[]},{"id":"12439","type":"CID","arg1_id":"12414","arg2_id":"12421","normalized":[]},{"id":"12440","type":"CID","arg1_id":"12416","arg2_id":"12409","normalized":[]},{"id":"12441","type":"CID","arg1_id":"12416","arg2_id":"12411","normalized":[]},{"id":"12442","type":"CID","arg1_id":"12416","arg2_id":"12415","normalized":[]},{"id":"12443","type":"CID","arg1_id":"12416","arg2_id":"12417","normalized":[]},{"id":"12444","type":"CID","arg1_id":"12416","arg2_id":"12419","normalized":[]},{"id":"12445","type":"CID","arg1_id":"12416","arg2_id":"12421","normalized":[]},{"id":"12446","type":"CID","arg1_id":"12418","arg2_id":"12409","normalized":[]},{"id":"12447","type":"CID","arg1_id":"12418","arg2_id":"12411","normalized":[]},{"id":"12448","type":"CID","arg1_id":"12418","arg2_id":"12415","normalized":[]},{"id":"12449","type":"CID","arg1_id":"12418","arg2_id":"12417","normalized":[]},{"id":"12450","type":"CID","arg1_id":"12418","arg2_id":"12419","normalized":[]},{"id":"12451","type":"CID","arg1_id":"12418","arg2_id":"12421","normalized":[]},{"id":"12452","type":"CID","arg1_id":"12420","arg2_id":"12409","normalized":[]},{"id":"12453","type":"CID","arg1_id":"12420","arg2_id":"12411","normalized":[]},{"id":"12454","type":"CID","arg1_id":"12420","arg2_id":"12415","normalized":[]},{"id":"12455","type":"CID","arg1_id":"12420","arg2_id":"12417","normalized":[]},{"id":"12456","type":"CID","arg1_id":"12420","arg2_id":"12419","normalized":[]},{"id":"12457","type":"CID","arg1_id":"12420","arg2_id":"12421","normalized":[]}]}
{"id":"12458","document_id":"14513889","passages":[{"id":"12459","type":"title","text":["Ketoconazole-induced neurologic sequelae."],"offsets":[[0,41]]},{"id":"12460","type":"abstract","text":["A 77-y-old patient developed weakness of extremities, legs paralysis, dysarthria and tremor 1 h after ingestion of 200 mg ketoconazole for the first time in his life. All complaints faded away within 24 h. Few days later, the patient used another 200 mg ketoconazole tablet, and within an hour experienced a similar clinical picture, which resolved again spontaneously within hours. Laboratory evaluations, including head CT scan, were normal. This case illustrates the need for close vigilance in adverse drug reactions, particularly in the elderly."],"offsets":[[42,592]]}],"entities":[{"id":"12461","type":"Chemical","text":["Ketoconazole"],"offsets":[[0,12]],"normalized":[{"db_name":"MESH","db_id":"D007654"}]},{"id":"12462","type":"Disease","text":["neurologic sequelae"],"offsets":[[21,40]],"normalized":[{"db_name":"MESH","db_id":"D009422"}]},{"id":"12463","type":"Disease","text":["weakness of extremities"],"offsets":[[71,94]],"normalized":[{"db_name":"MESH","db_id":"D018908"}]},{"id":"12464","type":"Disease","text":["legs paralysis"],"offsets":[[96,110]],"normalized":[{"db_name":"MESH","db_id":"D010243"}]},{"id":"12465","type":"Disease","text":["dysarthria"],"offsets":[[112,122]],"normalized":[{"db_name":"MESH","db_id":"D004401"}]},{"id":"12466","type":"Disease","text":["tremor"],"offsets":[[127,133]],"normalized":[{"db_name":"MESH","db_id":"D014202"}]},{"id":"12467","type":"Chemical","text":["ketoconazole"],"offsets":[[164,176]],"normalized":[{"db_name":"MESH","db_id":"D007654"}]},{"id":"12468","type":"Chemical","text":["ketoconazole"],"offsets":[[296,308]],"normalized":[{"db_name":"MESH","db_id":"D007654"}]},{"id":"12469","type":"Disease","text":["adverse drug reactions"],"offsets":[[540,562]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]}],"events":[],"coreferences":[],"relations":[{"id":"12470","type":"CID","arg1_id":"12461","arg2_id":"12465","normalized":[]},{"id":"12471","type":"CID","arg1_id":"12467","arg2_id":"12465","normalized":[]},{"id":"12472","type":"CID","arg1_id":"12468","arg2_id":"12465","normalized":[]},{"id":"12473","type":"CID","arg1_id":"12461","arg2_id":"12463","normalized":[]},{"id":"12474","type":"CID","arg1_id":"12467","arg2_id":"12463","normalized":[]},{"id":"12475","type":"CID","arg1_id":"12468","arg2_id":"12463","normalized":[]},{"id":"12476","type":"CID","arg1_id":"12461","arg2_id":"12466","normalized":[]},{"id":"12477","type":"CID","arg1_id":"12467","arg2_id":"12466","normalized":[]},{"id":"12478","type":"CID","arg1_id":"12468","arg2_id":"12466","normalized":[]},{"id":"12479","type":"CID","arg1_id":"12461","arg2_id":"12464","normalized":[]},{"id":"12480","type":"CID","arg1_id":"12467","arg2_id":"12464","normalized":[]},{"id":"12481","type":"CID","arg1_id":"12468","arg2_id":"12464","normalized":[]}]}
{"id":"12482","document_id":"15009014","passages":[{"id":"12483","type":"title","text":["Noxious chemical stimulation of rat facial mucosa increases intracranial blood flow through a trigemino-parasympathetic reflex--an experimental model for vascular dysfunctions in cluster headache."],"offsets":[[0,196]]},{"id":"12484","type":"abstract","text":["Cluster headache is characterized by typical autonomic dysfunctions including facial and intracranial vascular disturbances. Both the trigeminal and the cranial parasympathetic systems may be involved in mediating these dysfunctions. An experimental model was developed in the rat to measure changes in lacrimation and intracranial blood flow following noxious chemical stimulation of facial mucosa. Blood flow was monitored in arteries of the exposed cranial dura mater and the parietal cortex using laser Doppler flowmetry. Capsaicin (0.01-1 mm) applied to oral or nasal mucosa induced increases in dural and cortical blood flow and provoked lacrimation. These responses were blocked by systemic pre-administration of hexamethonium chloride (20 mg\/kg). The evoked increases in dural blood flow were also abolished by topical pre-administration of atropine (1 mm) and [Lys1, Pro2,5, Arg3,4, Tyr6]-VIP (0.1 mm), a vasoactive intestinal polypeptide (VIP) antagonist, onto the exposed dura mater. We conclude that noxious stimulation of facial mucosa increases intracranial blood flow and lacrimation via a trigemino-parasympathetic reflex. The blood flow responses seem to be mediated by the release of acetylcholine and VIP within the meninges. Similar mechanisms may be involved in the pathogenesis of cluster headache."],"offsets":[[197,1517]]}],"entities":[{"id":"12485","type":"Disease","text":["vascular dysfunctions"],"offsets":[[154,175]],"normalized":[{"db_name":"MESH","db_id":"D002561"}]},{"id":"12486","type":"Disease","text":["cluster headache"],"offsets":[[179,195]],"normalized":[{"db_name":"MESH","db_id":"D003027"}]},{"id":"12487","type":"Disease","text":["Cluster headache"],"offsets":[[197,213]],"normalized":[{"db_name":"MESH","db_id":"D003027"}]},{"id":"12488","type":"Disease","text":["intracranial vascular disturbances"],"offsets":[[286,320]],"normalized":[{"db_name":"MESH","db_id":"D002561"}]},{"id":"12489","type":"Chemical","text":["Capsaicin"],"offsets":[[723,732]],"normalized":[{"db_name":"MESH","db_id":"D002211"}]},{"id":"12490","type":"Disease","text":["increases in dural and cortical blood flow"],"offsets":[[785,827]],"normalized":[{"db_name":"MESH","db_id":"D006940"}]},{"id":"12491","type":"Chemical","text":["hexamethonium chloride"],"offsets":[[917,939]],"normalized":[{"db_name":"MESH","db_id":"D018738"}]},{"id":"12492","type":"Disease","text":["increases in dural blood flow"],"offsets":[[963,992]],"normalized":[{"db_name":"MESH","db_id":"D006940"}]},{"id":"12493","type":"Chemical","text":["atropine"],"offsets":[[1046,1054]],"normalized":[{"db_name":"MESH","db_id":"D001285"}]},{"id":"12494","type":"Chemical","text":["acetylcholine"],"offsets":[[1399,1412]],"normalized":[{"db_name":"MESH","db_id":"D000109"}]},{"id":"12495","type":"Disease","text":["cluster headache"],"offsets":[[1500,1516]],"normalized":[{"db_name":"MESH","db_id":"D003027"}]}],"events":[],"coreferences":[],"relations":[{"id":"12496","type":"CID","arg1_id":"12489","arg2_id":"12485","normalized":[]},{"id":"12497","type":"CID","arg1_id":"12489","arg2_id":"12488","normalized":[]},{"id":"12498","type":"CID","arg1_id":"12489","arg2_id":"12490","normalized":[]},{"id":"12499","type":"CID","arg1_id":"12489","arg2_id":"12492","normalized":[]}]}
{"id":"12500","document_id":"15120741","passages":[{"id":"12501","type":"title","text":["Recurrent excitation in the dentate gyrus of a murine model of temporal lobe epilepsy."],"offsets":[[0,86]]},{"id":"12502","type":"abstract","text":["Similar to rats, systemic pilocarpine injection causes status epilepticus (SE) and the eventual development of spontaneous seizures and mossy fiber sprouting in C57BL\/6 and CD1 mice, but the physiological correlates of these events have not been identified in mice. Population responses in granule cells of the dentate gyrus were examined in transverse slices of the ventral hippocampus from pilocarpine-treated and untreated mice. In Mg(2+)-free bathing medium containing bicuculline, conditions designed to increase excitability in the slices, electrical stimulation of the hilus resulted in a single population spike in granule cells from control mice and pilocarpine-treated mice that did not experience SE. In SE survivors, similar stimulation resulted in a population spike followed, at a variable latency, by negative DC shifts and repetitive afterdischarges of 3-60 s duration, which were blocked by ionotropic glutamate receptor antagonists. Focal glutamate photostimulation of the granule cell layer at sites distant from the recording pipette resulted in population responses of 1-30 s duration in slices from SE survivors but not other groups. These data support the hypothesis that SE-induced mossy fiber sprouting and synaptic reorganization are relevant characteristics of seizure development in these murine strains, resembling rat models of human temporal lobe epilepsy."],"offsets":[[87,1474]]}],"entities":[{"id":"12503","type":"Disease","text":["temporal lobe epilepsy"],"offsets":[[63,85]],"normalized":[{"db_name":"MESH","db_id":"D004833"}]},{"id":"12504","type":"Chemical","text":["pilocarpine"],"offsets":[[113,124]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"12505","type":"Disease","text":["status epilepticus"],"offsets":[[142,160]],"normalized":[{"db_name":"MESH","db_id":"D013226"}]},{"id":"12506","type":"Disease","text":["SE"],"offsets":[[162,164]],"normalized":[{"db_name":"MESH","db_id":"D013226"}]},{"id":"12507","type":"Disease","text":["seizures"],"offsets":[[210,218]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"12508","type":"Chemical","text":["pilocarpine"],"offsets":[[479,490]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"12509","type":"Chemical","text":["Mg"],"offsets":[[522,524]],"normalized":[{"db_name":"MESH","db_id":"D008274"}]},{"id":"12510","type":"Chemical","text":["bicuculline"],"offsets":[[560,571]],"normalized":[{"db_name":"MESH","db_id":"D001640"}]},{"id":"12511","type":"Chemical","text":["pilocarpine"],"offsets":[[746,757]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"12512","type":"Disease","text":["SE"],"offsets":[[795,797]],"normalized":[{"db_name":"MESH","db_id":"D013226"}]},{"id":"12513","type":"Disease","text":["SE"],"offsets":[[802,804]],"normalized":[{"db_name":"MESH","db_id":"D013226"}]},{"id":"12514","type":"Chemical","text":["glutamate"],"offsets":[[1006,1015]],"normalized":[{"db_name":"MESH","db_id":"D018698"}]},{"id":"12515","type":"Chemical","text":["glutamate"],"offsets":[[1044,1053]],"normalized":[{"db_name":"MESH","db_id":"D018698"}]},{"id":"12516","type":"Disease","text":["SE"],"offsets":[[1208,1210]],"normalized":[{"db_name":"MESH","db_id":"D013226"}]},{"id":"12517","type":"Disease","text":["SE"],"offsets":[[1282,1284]],"normalized":[{"db_name":"MESH","db_id":"D013226"}]},{"id":"12518","type":"Disease","text":["seizure"],"offsets":[[1375,1382]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"12519","type":"Disease","text":["temporal lobe epilepsy"],"offsets":[[1451,1473]],"normalized":[{"db_name":"MESH","db_id":"D004833"}]}],"events":[],"coreferences":[],"relations":[{"id":"12520","type":"CID","arg1_id":"12504","arg2_id":"12505","normalized":[]},{"id":"12521","type":"CID","arg1_id":"12504","arg2_id":"12506","normalized":[]},{"id":"12522","type":"CID","arg1_id":"12504","arg2_id":"12512","normalized":[]},{"id":"12523","type":"CID","arg1_id":"12504","arg2_id":"12513","normalized":[]},{"id":"12524","type":"CID","arg1_id":"12504","arg2_id":"12516","normalized":[]},{"id":"12525","type":"CID","arg1_id":"12504","arg2_id":"12517","normalized":[]},{"id":"12526","type":"CID","arg1_id":"12508","arg2_id":"12505","normalized":[]},{"id":"12527","type":"CID","arg1_id":"12508","arg2_id":"12506","normalized":[]},{"id":"12528","type":"CID","arg1_id":"12508","arg2_id":"12512","normalized":[]},{"id":"12529","type":"CID","arg1_id":"12508","arg2_id":"12513","normalized":[]},{"id":"12530","type":"CID","arg1_id":"12508","arg2_id":"12516","normalized":[]},{"id":"12531","type":"CID","arg1_id":"12508","arg2_id":"12517","normalized":[]},{"id":"12532","type":"CID","arg1_id":"12511","arg2_id":"12505","normalized":[]},{"id":"12533","type":"CID","arg1_id":"12511","arg2_id":"12506","normalized":[]},{"id":"12534","type":"CID","arg1_id":"12511","arg2_id":"12512","normalized":[]},{"id":"12535","type":"CID","arg1_id":"12511","arg2_id":"12513","normalized":[]},{"id":"12536","type":"CID","arg1_id":"12511","arg2_id":"12516","normalized":[]},{"id":"12537","type":"CID","arg1_id":"12511","arg2_id":"12517","normalized":[]},{"id":"12538","type":"CID","arg1_id":"12504","arg2_id":"12507","normalized":[]},{"id":"12539","type":"CID","arg1_id":"12504","arg2_id":"12518","normalized":[]},{"id":"12540","type":"CID","arg1_id":"12508","arg2_id":"12507","normalized":[]},{"id":"12541","type":"CID","arg1_id":"12508","arg2_id":"12518","normalized":[]},{"id":"12542","type":"CID","arg1_id":"12511","arg2_id":"12507","normalized":[]},{"id":"12543","type":"CID","arg1_id":"12511","arg2_id":"12518","normalized":[]}]}
{"id":"12544","document_id":"15275829","passages":[{"id":"12545","type":"title","text":["The alpha3 and beta4 nicotinic acetylcholine receptor subunits are necessary for nicotine-induced seizures and hypolocomotion in mice."],"offsets":[[0,134]]},{"id":"12546","type":"abstract","text":["Binding of nicotine to nicotinic acetylcholine receptors (nAChRs) elicits a series of dose-dependent behaviors that go from altered exploration, sedation, and tremors, to seizures and death. nAChRs are pentameric ion channels usually composed of alpha and beta subunits. A gene cluster comprises the alpha3, alpha5 and beta4 subunits, which coassemble to form functional receptors. We examined the role of the beta4 subunits in nicotine-induced seizures and hypolocomotion in beta4 homozygous null (beta4 -\/-) and alpha3 heterozygous (+\/-) mice. beta4 -\/- mice were less sensitive to the effects of nicotine both at low doses, measured as decreased exploration in an open field, and at high doses, measured as sensitivity to nicotine-induced seizures. Using in situ hybridization probes for the alpha3 and alpha5 subunits, we showed that alpha5 mRNA levels are unchanged, whereas alpha3 mRNA levels are selectively decreased in the mitral cell layer of the olfactory bulb, and the inferior and the superior colliculus of beta4 -\/- brains. alpha3 +\/- mice were partially resistant to nicotine-induced seizures when compared to wild-type littermates. mRNA levels for the alpha5 and the beta4 subunits were unchanged in alpha3 +\/- brains. Together, these results suggest that the beta4 and the alpha3 subunits are mediators of nicotine-induced seizures and hypolocomotion."],"offsets":[[135,1504]]}],"entities":[{"id":"12547","type":"Chemical","text":["acetylcholine"],"offsets":[[31,44]],"normalized":[{"db_name":"MESH","db_id":"D000109"}]},{"id":"12548","type":"Chemical","text":["nicotine"],"offsets":[[81,89]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"12549","type":"Disease","text":["seizures"],"offsets":[[98,106]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"12550","type":"Disease","text":["hypolocomotion"],"offsets":[[111,125]],"normalized":[{"db_name":"MESH","db_id":"D006948"}]},{"id":"12551","type":"Chemical","text":["nicotine"],"offsets":[[146,154]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"12552","type":"Chemical","text":["acetylcholine"],"offsets":[[168,181]],"normalized":[{"db_name":"MESH","db_id":"D000109"}]},{"id":"12553","type":"Disease","text":["tremors"],"offsets":[[294,301]],"normalized":[{"db_name":"MESH","db_id":"D014202"}]},{"id":"12554","type":"Disease","text":["seizures"],"offsets":[[306,314]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"12555","type":"Disease","text":["death"],"offsets":[[319,324]],"normalized":[{"db_name":"MESH","db_id":"D003643"}]},{"id":"12556","type":"Chemical","text":["nicotine"],"offsets":[[563,571]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"12557","type":"Disease","text":["seizures"],"offsets":[[580,588]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"12558","type":"Disease","text":["hypolocomotion"],"offsets":[[593,607]],"normalized":[{"db_name":"MESH","db_id":"D006948"}]},{"id":"12559","type":"Chemical","text":["nicotine"],"offsets":[[734,742]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"12560","type":"Chemical","text":["nicotine"],"offsets":[[860,868]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"12561","type":"Disease","text":["seizures"],"offsets":[[877,885]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"12562","type":"Chemical","text":["nicotine"],"offsets":[[1218,1226]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"12563","type":"Disease","text":["seizures"],"offsets":[[1235,1243]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"12564","type":"Chemical","text":["nicotine"],"offsets":[[1459,1467]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"12565","type":"Disease","text":["seizures"],"offsets":[[1476,1484]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"12566","type":"Disease","text":["hypolocomotion"],"offsets":[[1489,1503]],"normalized":[{"db_name":"MESH","db_id":"D006948"}]}],"events":[],"coreferences":[],"relations":[{"id":"12567","type":"CID","arg1_id":"12548","arg2_id":"12549","normalized":[]},{"id":"12568","type":"CID","arg1_id":"12548","arg2_id":"12554","normalized":[]},{"id":"12569","type":"CID","arg1_id":"12548","arg2_id":"12557","normalized":[]},{"id":"12570","type":"CID","arg1_id":"12548","arg2_id":"12561","normalized":[]},{"id":"12571","type":"CID","arg1_id":"12548","arg2_id":"12563","normalized":[]},{"id":"12572","type":"CID","arg1_id":"12548","arg2_id":"12565","normalized":[]},{"id":"12573","type":"CID","arg1_id":"12551","arg2_id":"12549","normalized":[]},{"id":"12574","type":"CID","arg1_id":"12551","arg2_id":"12554","normalized":[]},{"id":"12575","type":"CID","arg1_id":"12551","arg2_id":"12557","normalized":[]},{"id":"12576","type":"CID","arg1_id":"12551","arg2_id":"12561","normalized":[]},{"id":"12577","type":"CID","arg1_id":"12551","arg2_id":"12563","normalized":[]},{"id":"12578","type":"CID","arg1_id":"12551","arg2_id":"12565","normalized":[]},{"id":"12579","type":"CID","arg1_id":"12556","arg2_id":"12549","normalized":[]},{"id":"12580","type":"CID","arg1_id":"12556","arg2_id":"12554","normalized":[]},{"id":"12581","type":"CID","arg1_id":"12556","arg2_id":"12557","normalized":[]},{"id":"12582","type":"CID","arg1_id":"12556","arg2_id":"12561","normalized":[]},{"id":"12583","type":"CID","arg1_id":"12556","arg2_id":"12563","normalized":[]},{"id":"12584","type":"CID","arg1_id":"12556","arg2_id":"12565","normalized":[]},{"id":"12585","type":"CID","arg1_id":"12559","arg2_id":"12549","normalized":[]},{"id":"12586","type":"CID","arg1_id":"12559","arg2_id":"12554","normalized":[]},{"id":"12587","type":"CID","arg1_id":"12559","arg2_id":"12557","normalized":[]},{"id":"12588","type":"CID","arg1_id":"12559","arg2_id":"12561","normalized":[]},{"id":"12589","type":"CID","arg1_id":"12559","arg2_id":"12563","normalized":[]},{"id":"12590","type":"CID","arg1_id":"12559","arg2_id":"12565","normalized":[]},{"id":"12591","type":"CID","arg1_id":"12560","arg2_id":"12549","normalized":[]},{"id":"12592","type":"CID","arg1_id":"12560","arg2_id":"12554","normalized":[]},{"id":"12593","type":"CID","arg1_id":"12560","arg2_id":"12557","normalized":[]},{"id":"12594","type":"CID","arg1_id":"12560","arg2_id":"12561","normalized":[]},{"id":"12595","type":"CID","arg1_id":"12560","arg2_id":"12563","normalized":[]},{"id":"12596","type":"CID","arg1_id":"12560","arg2_id":"12565","normalized":[]},{"id":"12597","type":"CID","arg1_id":"12562","arg2_id":"12549","normalized":[]},{"id":"12598","type":"CID","arg1_id":"12562","arg2_id":"12554","normalized":[]},{"id":"12599","type":"CID","arg1_id":"12562","arg2_id":"12557","normalized":[]},{"id":"12600","type":"CID","arg1_id":"12562","arg2_id":"12561","normalized":[]},{"id":"12601","type":"CID","arg1_id":"12562","arg2_id":"12563","normalized":[]},{"id":"12602","type":"CID","arg1_id":"12562","arg2_id":"12565","normalized":[]},{"id":"12603","type":"CID","arg1_id":"12564","arg2_id":"12549","normalized":[]},{"id":"12604","type":"CID","arg1_id":"12564","arg2_id":"12554","normalized":[]},{"id":"12605","type":"CID","arg1_id":"12564","arg2_id":"12557","normalized":[]},{"id":"12606","type":"CID","arg1_id":"12564","arg2_id":"12561","normalized":[]},{"id":"12607","type":"CID","arg1_id":"12564","arg2_id":"12563","normalized":[]},{"id":"12608","type":"CID","arg1_id":"12564","arg2_id":"12565","normalized":[]}]}
{"id":"12609","document_id":"15602202","passages":[{"id":"12610","type":"title","text":["Recurrent acute interstitial nephritis induced by azithromycin."],"offsets":[[0,63]]},{"id":"12611","type":"abstract","text":["A 14-year-old girl is reported with recurrent, azithromycin-induced, acute interstitial nephritis. The second episode was more severe than the first; and although both were treated with intensive corticosteroid therapy, renal function remained impaired. Although most cases of antibiotic induced acute interstitial nephritis are benign and self-limited, some patients are at risk for permanent renal injury."],"offsets":[[64,471]]}],"entities":[{"id":"12612","type":"Disease","text":["interstitial nephritis"],"offsets":[[16,38]],"normalized":[{"db_name":"MESH","db_id":"D009395"}]},{"id":"12613","type":"Chemical","text":["azithromycin"],"offsets":[[50,62]],"normalized":[{"db_name":"MESH","db_id":"D017963"}]},{"id":"12614","type":"Chemical","text":["azithromycin"],"offsets":[[111,123]],"normalized":[{"db_name":"MESH","db_id":"D017963"}]},{"id":"12615","type":"Disease","text":["interstitial nephritis"],"offsets":[[139,161]],"normalized":[{"db_name":"MESH","db_id":"D009395"}]},{"id":"12616","type":"Disease","text":["interstitial nephritis"],"offsets":[[366,388]],"normalized":[{"db_name":"MESH","db_id":"D009395"}]},{"id":"12617","type":"Disease","text":["renal injury"],"offsets":[[458,470]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]}],"events":[],"coreferences":[],"relations":[{"id":"12618","type":"CID","arg1_id":"12613","arg2_id":"12612","normalized":[]},{"id":"12619","type":"CID","arg1_id":"12613","arg2_id":"12615","normalized":[]},{"id":"12620","type":"CID","arg1_id":"12613","arg2_id":"12616","normalized":[]},{"id":"12621","type":"CID","arg1_id":"12614","arg2_id":"12612","normalized":[]},{"id":"12622","type":"CID","arg1_id":"12614","arg2_id":"12615","normalized":[]},{"id":"12623","type":"CID","arg1_id":"12614","arg2_id":"12616","normalized":[]}]}
{"id":"12624","document_id":"16181582","passages":[{"id":"12625","type":"title","text":["Valproate-induced encephalopathy."],"offsets":[[0,33]]},{"id":"12626","type":"abstract","text":["Valproate-induced encephalopathy is a rare syndrome that may manifest in otherwise normal epileptic individuals. It may even present in patients who have tolerated this medicine well in the past. It is usually but not necessarily associated with hyperammonemia. The EEG shows characteristic triphasic waves in most patients with this complication. A case of valproate-induced encephalopathy is presented. The problems in diagnosing this condition are subsequently discussed."],"offsets":[[34,508]]}],"entities":[{"id":"12627","type":"Chemical","text":["Valproate"],"offsets":[[0,9]],"normalized":[{"db_name":"MESH","db_id":"D014635"}]},{"id":"12628","type":"Disease","text":["encephalopathy"],"offsets":[[18,32]],"normalized":[{"db_name":"MESH","db_id":"D001927"}]},{"id":"12629","type":"Chemical","text":["Valproate"],"offsets":[[34,43]],"normalized":[{"db_name":"MESH","db_id":"D014635"}]},{"id":"12630","type":"Disease","text":["encephalopathy"],"offsets":[[52,66]],"normalized":[{"db_name":"MESH","db_id":"D001927"}]},{"id":"12631","type":"Disease","text":["epileptic"],"offsets":[[124,133]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"12632","type":"Disease","text":["hyperammonemia"],"offsets":[[280,294]],"normalized":[{"db_name":"MESH","db_id":"D022124"}]},{"id":"12633","type":"Chemical","text":["valproate"],"offsets":[[392,401]],"normalized":[{"db_name":"MESH","db_id":"D014635"}]},{"id":"12634","type":"Disease","text":["encephalopathy"],"offsets":[[410,424]],"normalized":[{"db_name":"MESH","db_id":"D001927"}]}],"events":[],"coreferences":[],"relations":[{"id":"12635","type":"CID","arg1_id":"12627","arg2_id":"12628","normalized":[]},{"id":"12636","type":"CID","arg1_id":"12627","arg2_id":"12630","normalized":[]},{"id":"12637","type":"CID","arg1_id":"12627","arg2_id":"12634","normalized":[]},{"id":"12638","type":"CID","arg1_id":"12629","arg2_id":"12628","normalized":[]},{"id":"12639","type":"CID","arg1_id":"12629","arg2_id":"12630","normalized":[]},{"id":"12640","type":"CID","arg1_id":"12629","arg2_id":"12634","normalized":[]},{"id":"12641","type":"CID","arg1_id":"12633","arg2_id":"12628","normalized":[]},{"id":"12642","type":"CID","arg1_id":"12633","arg2_id":"12630","normalized":[]},{"id":"12643","type":"CID","arg1_id":"12633","arg2_id":"12634","normalized":[]}]}
{"id":"12644","document_id":"16298782","passages":[{"id":"12645","type":"title","text":["Nitro-L-arginine methyl ester: a potential protector against gentamicin ototoxicity."],"offsets":[[0,84]]},{"id":"12646","type":"abstract","text":["The nitric oxide (NO) inhibitor nitro-L-arginine methyl ester (L-NAME) may act as an otoprotectant against high-frequency hearing loss caused by gentamicin, but further studies are needed to confirm this.Aminoglycoside antibiotics are still widely used by virtue of their efficacy and low cost. Their ototoxicity is a serious health problem and, as their ototoxic mechanism involves the production of NO, we need to assess the use of NO inhibitors for the prevention of aminoglycoside-induced sensorineural hearing loss. In this experimental study we used 30 Sprague-Dawley rats, 27 of which had gentamicin instilled into the middle ear. The otoprotectant L-NAME was administered topically to 12\/27 animals. Its effect was determined in terms of attenuation of hearing loss, measured by shifts in the auditory brainstem response threshold. L-NAME reduced gentamicin-induced hearing loss in the high-frequency range, but gave no protection in the middle or low frequencies."],"offsets":[[85,1057]]}],"entities":[{"id":"12647","type":"Chemical","text":["Nitro-L-arginine methyl ester"],"offsets":[[0,29]],"normalized":[{"db_name":"MESH","db_id":"D019331"}]},{"id":"12648","type":"Chemical","text":["gentamicin"],"offsets":[[61,71]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"12649","type":"Disease","text":["ototoxicity"],"offsets":[[72,83]],"normalized":[{"db_name":"MESH","db_id":"D006311"}]},{"id":"12650","type":"Chemical","text":["nitric oxide"],"offsets":[[89,101]],"normalized":[{"db_name":"MESH","db_id":"D009569"}]},{"id":"12651","type":"Chemical","text":["NO"],"offsets":[[103,105]],"normalized":[{"db_name":"MESH","db_id":"D009569"}]},{"id":"12652","type":"Chemical","text":["nitro-L-arginine methyl ester"],"offsets":[[117,146]],"normalized":[{"db_name":"MESH","db_id":"D019331"}]},{"id":"12653","type":"Chemical","text":["L-NAME"],"offsets":[[148,154]],"normalized":[{"db_name":"MESH","db_id":"D019331"}]},{"id":"12654","type":"Disease","text":["high-frequency hearing loss"],"offsets":[[192,219]],"normalized":[{"db_name":"MESH","db_id":"D006316"}]},{"id":"12655","type":"Chemical","text":["gentamicin"],"offsets":[[230,240]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"12656","type":"Chemical","text":["Aminoglycoside"],"offsets":[[289,303]],"normalized":[{"db_name":"MESH","db_id":"D000617"}]},{"id":"12657","type":"Disease","text":["ototoxicity"],"offsets":[[386,397]],"normalized":[{"db_name":"MESH","db_id":"D006311"}]},{"id":"12658","type":"Disease","text":["ototoxic"],"offsets":[[440,448]],"normalized":[{"db_name":"MESH","db_id":"D006311"}]},{"id":"12659","type":"Chemical","text":["NO"],"offsets":[[486,488]],"normalized":[{"db_name":"MESH","db_id":"D009569"}]},{"id":"12660","type":"Chemical","text":["NO"],"offsets":[[519,521]],"normalized":[{"db_name":"MESH","db_id":"D009569"}]},{"id":"12661","type":"Chemical","text":["aminoglycoside"],"offsets":[[555,569]],"normalized":[{"db_name":"MESH","db_id":"D000617"}]},{"id":"12662","type":"Disease","text":["sensorineural hearing loss"],"offsets":[[578,604]],"normalized":[{"db_name":"MESH","db_id":"D006319"}]},{"id":"12663","type":"Chemical","text":["gentamicin"],"offsets":[[681,691]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"12664","type":"Chemical","text":["L-NAME"],"offsets":[[741,747]],"normalized":[{"db_name":"MESH","db_id":"D019331"}]},{"id":"12665","type":"Disease","text":["hearing loss"],"offsets":[[846,858]],"normalized":[{"db_name":"MESH","db_id":"D034381"}]},{"id":"12666","type":"Chemical","text":["L-NAME"],"offsets":[[925,931]],"normalized":[{"db_name":"MESH","db_id":"D019331"}]},{"id":"12667","type":"Chemical","text":["gentamicin"],"offsets":[[940,950]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"12668","type":"Disease","text":["hearing loss"],"offsets":[[959,971]],"normalized":[{"db_name":"MESH","db_id":"D034381"}]}],"events":[],"coreferences":[],"relations":[{"id":"12669","type":"CID","arg1_id":"12648","arg2_id":"12665","normalized":[]},{"id":"12670","type":"CID","arg1_id":"12648","arg2_id":"12668","normalized":[]},{"id":"12671","type":"CID","arg1_id":"12655","arg2_id":"12665","normalized":[]},{"id":"12672","type":"CID","arg1_id":"12655","arg2_id":"12668","normalized":[]},{"id":"12673","type":"CID","arg1_id":"12663","arg2_id":"12665","normalized":[]},{"id":"12674","type":"CID","arg1_id":"12663","arg2_id":"12668","normalized":[]},{"id":"12675","type":"CID","arg1_id":"12667","arg2_id":"12665","normalized":[]},{"id":"12676","type":"CID","arg1_id":"12667","arg2_id":"12668","normalized":[]}]}
{"id":"12677","document_id":"16428221","passages":[{"id":"12678","type":"title","text":["Cerebral vasculitis following oral methylphenidate intake in an adult: a case report."],"offsets":[[0,85]]},{"id":"12679","type":"abstract","text":["Methylphenidate is structurally and functionally similar to amphetamine. Cerebral vasculitis associated with amphetamine abuse is well documented, and in rare cases ischaemic stroke has been reported after methylphenidate intake in children. We report the case of a 63-year-old female who was treated with methylphenidate due to hyperactivity and suffered from multiple ischaemic strokes. We consider drug-induced cerebral vasculitis as the most likely cause of recurrent ischaemic strokes in the absence of any pathological findings during the diagnostic work-up. We conclude that methylphenidate mediated vasculitis should be considered in patients with neurological symptoms and a history of methylphenidate therapy. This potential side-effect, though very rare, represents one more reason to be very restrictive in the use of methylphenidate."],"offsets":[[86,932]]}],"entities":[{"id":"12680","type":"Disease","text":["Cerebral vasculitis"],"offsets":[[0,19]],"normalized":[{"db_name":"MESH","db_id":"D020293"}]},{"id":"12681","type":"Chemical","text":["methylphenidate"],"offsets":[[35,50]],"normalized":[{"db_name":"MESH","db_id":"D008774"}]},{"id":"12682","type":"Chemical","text":["Methylphenidate"],"offsets":[[86,101]],"normalized":[{"db_name":"MESH","db_id":"D008774"}]},{"id":"12683","type":"Chemical","text":["amphetamine"],"offsets":[[146,157]],"normalized":[{"db_name":"MESH","db_id":"D000661"}]},{"id":"12684","type":"Disease","text":["Cerebral vasculitis"],"offsets":[[159,178]],"normalized":[{"db_name":"MESH","db_id":"D020293"}]},{"id":"12685","type":"Disease","text":["amphetamine abuse"],"offsets":[[195,212]],"normalized":[{"db_name":"MESH","db_id":"D019969"}]},{"id":"12686","type":"Disease","text":["ischaemic stroke"],"offsets":[[251,267]],"normalized":[{"db_name":"MESH","db_id":"D002544"}]},{"id":"12687","type":"Chemical","text":["methylphenidate"],"offsets":[[292,307]],"normalized":[{"db_name":"MESH","db_id":"D008774"}]},{"id":"12688","type":"Chemical","text":["methylphenidate"],"offsets":[[392,407]],"normalized":[{"db_name":"MESH","db_id":"D008774"}]},{"id":"12689","type":"Disease","text":["hyperactivity"],"offsets":[[415,428]],"normalized":[{"db_name":"MESH","db_id":"D006948"}]},{"id":"12690","type":"Disease","text":["ischaemic strokes"],"offsets":[[456,473]],"normalized":[{"db_name":"MESH","db_id":"D002544"}]},{"id":"12691","type":"Disease","text":["cerebral vasculitis"],"offsets":[[500,519]],"normalized":[{"db_name":"MESH","db_id":"D020293"}]},{"id":"12692","type":"Disease","text":["ischaemic strokes"],"offsets":[[558,575]],"normalized":[{"db_name":"MESH","db_id":"D002544"}]},{"id":"12693","type":"Chemical","text":["methylphenidate"],"offsets":[[668,683]],"normalized":[{"db_name":"MESH","db_id":"D008774"}]},{"id":"12694","type":"Disease","text":["vasculitis"],"offsets":[[693,703]],"normalized":[{"db_name":"MESH","db_id":"D014657"}]},{"id":"12695","type":"Chemical","text":["methylphenidate"],"offsets":[[781,796]],"normalized":[{"db_name":"MESH","db_id":"D008774"}]},{"id":"12696","type":"Chemical","text":["methylphenidate"],"offsets":[[916,931]],"normalized":[{"db_name":"MESH","db_id":"D008774"}]}],"events":[],"coreferences":[],"relations":[{"id":"12697","type":"CID","arg1_id":"12681","arg2_id":"12680","normalized":[]},{"id":"12698","type":"CID","arg1_id":"12681","arg2_id":"12684","normalized":[]},{"id":"12699","type":"CID","arg1_id":"12681","arg2_id":"12691","normalized":[]},{"id":"12700","type":"CID","arg1_id":"12682","arg2_id":"12680","normalized":[]},{"id":"12701","type":"CID","arg1_id":"12682","arg2_id":"12684","normalized":[]},{"id":"12702","type":"CID","arg1_id":"12682","arg2_id":"12691","normalized":[]},{"id":"12703","type":"CID","arg1_id":"12687","arg2_id":"12680","normalized":[]},{"id":"12704","type":"CID","arg1_id":"12687","arg2_id":"12684","normalized":[]},{"id":"12705","type":"CID","arg1_id":"12687","arg2_id":"12691","normalized":[]},{"id":"12706","type":"CID","arg1_id":"12688","arg2_id":"12680","normalized":[]},{"id":"12707","type":"CID","arg1_id":"12688","arg2_id":"12684","normalized":[]},{"id":"12708","type":"CID","arg1_id":"12688","arg2_id":"12691","normalized":[]},{"id":"12709","type":"CID","arg1_id":"12693","arg2_id":"12680","normalized":[]},{"id":"12710","type":"CID","arg1_id":"12693","arg2_id":"12684","normalized":[]},{"id":"12711","type":"CID","arg1_id":"12693","arg2_id":"12691","normalized":[]},{"id":"12712","type":"CID","arg1_id":"12695","arg2_id":"12680","normalized":[]},{"id":"12713","type":"CID","arg1_id":"12695","arg2_id":"12684","normalized":[]},{"id":"12714","type":"CID","arg1_id":"12695","arg2_id":"12691","normalized":[]},{"id":"12715","type":"CID","arg1_id":"12696","arg2_id":"12680","normalized":[]},{"id":"12716","type":"CID","arg1_id":"12696","arg2_id":"12684","normalized":[]},{"id":"12717","type":"CID","arg1_id":"12696","arg2_id":"12691","normalized":[]}]}
{"id":"12718","document_id":"16858720","passages":[{"id":"12719","type":"title","text":["Cerebral haemorrhage induced by warfarin - the influence of drug-drug interactions."],"offsets":[[0,83]]},{"id":"12720","type":"abstract","text":["PURPOSE: To evaluate the frequency, severity and preventability of warfarin-induced cerebral haemorrhages due to warfarin and warfarin-drug interactions in patients living in the county of Osterg  tland, Sweden. METHODS: All patients with a diagnosed cerebral haemorrhage at three hospitals during the period 2000-2002 were identified. Medical records were studied retrospectively to evaluate whether warfarin and warfarin-drug interactions could have caused the cerebral haemorrhage. The proportion of possibly avoidable cases due to drug interactions was estimated. RESULTS: Among 593 patients with cerebral haemorrhage, 59 (10%) were assessed as related to warfarin treatment. This imply an incidence of 1.7\/100,000 treatment years. Of the 59 cases, 26 (44%) had a fatal outcome, compared to 136 (25%) among the non-warfarin patients (p < 0.01). A warfarin-drug interaction could have contributed to the haemorrhage in 24 (41%) of the warfarin patients and in 7 of these (12%) the bleeding complication was considered being possible to avoid. CONCLUSIONS: Warfarin-induced cerebral haemorrhages are a major clinical problem with a high fatality rate. Almost half of the cases was related to a warfarin-drug interaction. A significant proportion of warfarin-related cerebral haemorrhages might have been prevented if greater caution had been taken when prescribing drugs known to interact with warfarin."],"offsets":[[84,1489]]}],"entities":[{"id":"12721","type":"Disease","text":["Cerebral haemorrhage"],"offsets":[[0,20]],"normalized":[{"db_name":"MESH","db_id":"D002543"}]},{"id":"12722","type":"Chemical","text":["warfarin"],"offsets":[[32,40]],"normalized":[{"db_name":"MESH","db_id":"D014859"}]},{"id":"12723","type":"Chemical","text":["warfarin"],"offsets":[[151,159]],"normalized":[{"db_name":"MESH","db_id":"D014859"}]},{"id":"12724","type":"Disease","text":["cerebral haemorrhages"],"offsets":[[168,189]],"normalized":[{"db_name":"MESH","db_id":"D002543"}]},{"id":"12725","type":"Chemical","text":["warfarin"],"offsets":[[197,205]],"normalized":[{"db_name":"MESH","db_id":"D014859"}]},{"id":"12726","type":"Chemical","text":["warfarin"],"offsets":[[210,218]],"normalized":[{"db_name":"MESH","db_id":"D014859"}]},{"id":"12727","type":"Disease","text":["cerebral haemorrhage"],"offsets":[[335,355]],"normalized":[{"db_name":"MESH","db_id":"D002543"}]},{"id":"12728","type":"Chemical","text":["warfarin"],"offsets":[[485,493]],"normalized":[{"db_name":"MESH","db_id":"D014859"}]},{"id":"12729","type":"Chemical","text":["warfarin"],"offsets":[[498,506]],"normalized":[{"db_name":"MESH","db_id":"D014859"}]},{"id":"12730","type":"Disease","text":["cerebral haemorrhage"],"offsets":[[547,567]],"normalized":[{"db_name":"MESH","db_id":"D002543"}]},{"id":"12731","type":"Disease","text":["cerebral 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{"id":"12842","document_id":"17466854","passages":[{"id":"12843","type":"title","text":["Side effects of postoperative administration of methylprednisolone and gentamicin into the posterior sub-Tenon's space."],"offsets":[[0,119]]},{"id":"12844","type":"abstract","text":["PURPOSE: To assess the incidence of postoperative emetic side effects after the administration of methylprednisolone and gentamicin into the posterior sub-Tenon's space at the end of routine cataract surgery. SETTING: St. Luke's Hospital, Gwardamangia, Malta. METHODS: A double-blind double-armed prospective study comprised 40 patients who had uneventful sutureless phacoemulsification under sub-Tenon's local infiltration of 3 mL of plain lignocaine. At the end of the procedure, Group A (n = 20) had 20 mg\/0.5 mL of methylprednisolone and 10 mg\/0.5 mL of gentamicin injected into the posterior sub-Tenon's space and Group B (n = 20) had the same combination injected into the anterior sub-Tenon's space. Postoperatively, all patients were assessed for symptoms of nausea, vomiting, and headache. A chi-square test was used to assess the statistical significance of results. RESULTS: Sixty percent in Group A developed postoperative emetic symptoms, headache, or both; 1 patient in Group B developed symptoms. CONCLUSIONS: The administration of methylprednisolone and gentamicin in the posterior sub-Tenon's space was related to a high incidence of side effects including nausea, vomiting, and headache. All adverse effects were self-limiting."],"offsets":[[120,1365]]}],"entities":[{"id":"12845","type":"Chemical","text":["methylprednisolone"],"offsets":[[48,66]],"normalized":[{"db_name":"MESH","db_id":"D008775"}]},{"id":"12846","type":"Chemical","text":["gentamicin"],"offsets":[[71,81]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"12847","type":"Chemical","text":["methylprednisolone"],"offsets":[[218,236]],"normalized":[{"db_name":"MESH","db_id":"D008775"}]},{"id":"12848","type":"Chemical","text":["gentamicin"],"offsets":[[241,251]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"12849","type":"Disease","text":["cataract"],"offsets":[[311,319]],"normalized":[{"db_name":"MESH","db_id":"D002386"}]},{"id":"12850","type":"Chemical","text":["lignocaine"],"offsets":[[561,571]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"12851","type":"Chemical","text":["methylprednisolone"],"offsets":[[639,657]],"normalized":[{"db_name":"MESH","db_id":"D008775"}]},{"id":"12852","type":"Chemical","text":["gentamicin"],"offsets":[[678,688]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"12853","type":"Disease","text":["nausea, vomiting"],"offsets":[[887,903]],"normalized":[{"db_name":"MESH","db_id":"D020250"}]},{"id":"12854","type":"Disease","text":["headache"],"offsets":[[909,917]],"normalized":[{"db_name":"MESH","db_id":"D006261"}]},{"id":"12855","type":"Disease","text":["postoperative emetic symptoms"],"offsets":[[1041,1070]],"normalized":[{"db_name":"MESH","db_id":"D020250"}]},{"id":"12856","type":"Disease","text":["headache"],"offsets":[[1072,1080]],"normalized":[{"db_name":"MESH","db_id":"D006261"}]},{"id":"12857","type":"Chemical","text":["methylprednisolone"],"offsets":[[1167,1185]],"normalized":[{"db_name":"MESH","db_id":"D008775"}]},{"id":"12858","type":"Chemical","text":["gentamicin"],"offsets":[[1190,1200]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"12859","type":"Disease","text":["nausea, 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{"id":"12909","document_id":"17562951","passages":[{"id":"12910","type":"title","text":["Cardiac Angiography in Renally Impaired Patients (CARE) study: a randomized double-blind trial of contrast-induced nephropathy in patients with chronic kidney disease."],"offsets":[[0,167]]},{"id":"12911","type":"abstract","text":["BACKGROUND: No direct comparisons exist of the renal tolerability of the low-osmolality contrast medium iopamidol with that of the iso-osmolality contrast medium iodixanol in high-risk patients. METHODS AND RESULTS: The present study is a multicenter, randomized, double-blind comparison of iopamidol and iodixanol in patients with chronic kidney disease (estimated glomerular filtration rate, 20 to 59 mL\/min) who underwent cardiac angiography or percutaneous coronary interventions. Serum creatinine (SCr) levels and estimated glomerular filtration rate were assessed at baseline and 2 to 5 days after receiving medications. The primary outcome was a postdose SCr increase > or = 0.5 mg\/dL (44.2 micromol\/L) over baseline. Secondary outcomes were a postdose SCr increase > or = 25%, a postdose estimated glomerular filtration rate decrease of > or = 25%, and the mean peak change in SCr. In 414 patients, contrast volume, presence of diabetes mellitus, use of N-acetylcysteine, mean baseline SCr, and estimated glomerular filtration rate were comparable in the 2 groups. SCr increases > or = 0.5 mg\/dL occurred in 4.4% (9 of 204 patients) after iopamidol and 6.7% (14 of 210 patients) after iodixanol (P=0.39), whereas rates of SCr increases > or = 25% were 9.8% and 12.4%, respectively (P=0.44). In patients with diabetes, SCr increases > or = 0.5 mg\/dL were 5.1% (4 of 78 patients) with iopamidol and 13.0% (12 of 92 patients) with iodixanol (P=0.11), whereas SCr increases > or = 25% were 10.3% and 15.2%, respectively (P=0.37). Mean post-SCr increases were significantly less with iopamidol (all patients: 0.07 versus 0.12 mg\/dL, 6.2 versus 10.6 micromol\/L, P=0.03; patients with diabetes: 0.07 versus 0.16 mg\/dL, 6.2 versus 14.1 micromol\/L, P=0.01). CONCLUSIONS: The rate of contrast-induced nephropathy, defined by multiple end points, is not statistically different after the intraarterial administration of iopamidol or iodixanol to high-risk patients, with or without diabetes mellitus. Any true difference between the agents is small and not likely to be clinically significant."],"offsets":[[168,2258]]}],"entities":[{"id":"12912","type":"Disease","text":["nephropathy"],"offsets":[[115,126]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"12913","type":"Disease","text":["chronic kidney disease"],"offsets":[[144,166]],"normalized":[{"db_name":"MESH","db_id":"D051436"}]},{"id":"12914","type":"Chemical","text":["contrast medium"],"offsets":[[256,271]],"normalized":[{"db_name":"MESH","db_id":"D003287"}]},{"id":"12915","type":"Chemical","text":["iopamidol"],"offsets":[[272,281]],"normalized":[{"db_name":"MESH","db_id":"D007479"}]},{"id":"12916","type":"Chemical","text":["contrast medium"],"offsets":[[314,329]],"normalized":[{"db_name":"MESH","db_id":"D003287"}]},{"id":"12917","type":"Chemical","text":["iodixanol"],"offsets":[[330,339]],"normalized":[{"db_name":"MESH","db_id":"C044834"}]},{"id":"12918","type":"Chemical","text":["iopamidol"],"offsets":[[459,468]],"normalized":[{"db_name":"MESH","db_id":"D007479"}]},{"id":"12919","type":"Chemical","text":["iodixanol"],"offsets":[[473,482]],"normalized":[{"db_name":"MESH","db_id":"C044834"}]},{"id":"12920","type":"Disease","text":["chronic kidney disease"],"offsets":[[500,522]],"normalized":[{"db_name":"MESH","db_id":"D051436"}]},{"id":"12921","type":"Chemical","text":["creatinine"],"offsets":[[659,669]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"12922","type":"Disease","text":["diabetes mellitus"],"offsets":[[1104,1121]],"normalized":[{"db_name":"MESH","db_id":"D003920"}]},{"id":"12923","type":"Chemical","text":["N-acetylcysteine"],"offsets":[[1130,1146]],"normalized":[{"db_name":"MESH","db_id":"D000111"}]},{"id":"12924","type":"Chemical","text":["iopamidol"],"offsets":[[1315,1324]],"normalized":[{"db_name":"MESH","db_id":"D007479"}]},{"id":"12925","type":"Chemical","text":["iodixanol"],"offsets":[[1361,1370]],"normalized":[{"db_name":"MESH","db_id":"C044834"}]},{"id":"12926","type":"Disease","text":["diabetes"],"offsets":[[1484,1492]],"normalized":[{"db_name":"MESH","db_id":"D003920"}]},{"id":"12927","type":"Chemical","text":["iopamidol"],"offsets":[[1559,1568]],"normalized":[{"db_name":"MESH","db_id":"D007479"}]},{"id":"12928","type":"Chemical","text":["iodixanol"],"offsets":[[1604,1613]],"normalized":[{"db_name":"MESH","db_id":"C044834"}]},{"id":"12929","type":"Chemical","text":["iopamidol"],"offsets":[[1755,1764]],"normalized":[{"db_name":"MESH","db_id":"D007479"}]},{"id":"12930","type":"Disease","text":["diabetes"],"offsets":[[1854,1862]],"normalized":[{"db_name":"MESH","db_id":"D003920"}]},{"id":"12931","type":"Disease","text":["nephropathy"],"offsets":[[1967,1978]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"12932","type":"Chemical","text":["iopamidol"],"offsets":[[2085,2094]],"normalized":[{"db_name":"MESH","db_id":"D007479"}]},{"id":"12933","type":"Chemical","text":["iodixanol"],"offsets":[[2098,2107]],"normalized":[{"db_name":"MESH","db_id":"C044834"}]},{"id":"12934","type":"Disease","text":["diabetes mellitus"],"offsets":[[2147,2164]],"normalized":[{"db_name":"MESH","db_id":"D003920"}]}],"events":[],"coreferences":[],"relations":[{"id":"12935","type":"CID","arg1_id":"12917","arg2_id":"12912","normalized":[]},{"id":"12936","type":"CID","arg1_id":"12917","arg2_id":"12931","normalized":[]},{"id":"12937","type":"CID","arg1_id":"12919","arg2_id":"12912","normalized":[]},{"id":"12938","type":"CID","arg1_id":"12919","arg2_id":"12931","normalized":[]},{"id":"12939","type":"CID","arg1_id":"12925","arg2_id":"12912","normalized":[]},{"id":"12940","type":"CID","arg1_id":"12925","arg2_id":"12931","normalized":[]},{"id":"12941","type":"CID","arg1_id":"12928","arg2_id":"12912","normalized":[]},{"id":"12942","type":"CID","arg1_id":"12928","arg2_id":"12931","normalized":[]},{"id":"12943","type":"CID","arg1_id":"12933","arg2_id":"12912","normalized":[]},{"id":"12944","type":"CID","arg1_id":"12933","arg2_id":"12931","normalized":[]},{"id":"12945","type":"CID","arg1_id":"12914","arg2_id":"12912","normalized":[]},{"id":"12946","type":"CID","arg1_id":"12914","arg2_id":"12931","normalized":[]},{"id":"12947","type":"CID","arg1_id":"12916","arg2_id":"12912","normalized":[]},{"id":"12948","type":"CID","arg1_id":"12916","arg2_id":"12931","normalized":[]},{"id":"12949","type":"CID","arg1_id":"12915","arg2_id":"12912","normalized":[]},{"id":"12950","type":"CID","arg1_id":"12915","arg2_id":"12931","normalized":[]},{"id":"12951","type":"CID","arg1_id":"12918","arg2_id":"12912","normalized":[]},{"id":"12952","type":"CID","arg1_id":"12918","arg2_id":"12931","normalized":[]},{"id":"12953","type":"CID","arg1_id":"12924","arg2_id":"12912","normalized":[]},{"id":"12954","type":"CID","arg1_id":"12924","arg2_id":"12931","normalized":[]},{"id":"12955","type":"CID","arg1_id":"12927","arg2_id":"12912","normalized":[]},{"id":"12956","type":"CID","arg1_id":"12927","arg2_id":"12931","normalized":[]},{"id":"12957","type":"CID","arg1_id":"12929","arg2_id":"12912","normalized":[]},{"id":"12958","type":"CID","arg1_id":"12929","arg2_id":"12931","normalized":[]},{"id":"12959","type":"CID","arg1_id":"12932","arg2_id":"12912","normalized":[]},{"id":"12960","type":"CID","arg1_id":"12932","arg2_id":"12931","normalized":[]}]}
{"id":"12961","document_id":"17600377","passages":[{"id":"12962","type":"title","text":["A novel compound, maltolyl p-coumarate, attenuates cognitive deficits and shows neuroprotective effects in vitro and in vivo dementia models."],"offsets":[[0,141]]},{"id":"12963","type":"abstract","text":["To develop a novel and effective drug that could enhance cognitive function and neuroprotection, we newly synthesized maltolyl p-coumarate by the esterification of maltol and p-coumaric acid. In the present study, we investigated whether maltolyl p-coumarate could improve cognitive decline in scopolamine-injected rats and in amyloid beta peptide(1-42)-infused rats. Maltolyl p-coumarate was found to attenuate cognitive deficits in both rat models using passive avoidance test and to reduce apoptotic cell death observed in the hippocampus of the amyloid beta peptide(1-42)-infused rats. We also examined the neuroprotective effects of maltolyl p-coumarate in vitro using SH-SY5Y cells. Cells were pretreated with maltolyl p-coumarate, before exposed to amyloid beta peptide(1-42), glutamate or H2O2. We found that maltolyl p-coumarate significantly decreased apoptotic cell death and reduced reactive oxygen species, cytochrome c release, and caspase 3 activation. Taking these in vitro and in vivo results together, our study suggests that maltolyl p-coumarate is a potentially effective candidate against Alzheimer's disease that is characterized by wide spread neuronal death and progressive decline of cognitive function."],"offsets":[[142,1370]]}],"entities":[{"id":"12964","type":"Chemical","text":["maltolyl p-coumarate"],"offsets":[[18,38]],"normalized":[{"db_name":"MESH","db_id":"C524754"}]},{"id":"12965","type":"Disease","text":["cognitive deficits"],"offsets":[[51,69]],"normalized":[{"db_name":"MESH","db_id":"D003072"}]},{"id":"12966","type":"Disease","text":["dementia"],"offsets":[[125,133]],"normalized":[{"db_name":"MESH","db_id":"D003704"}]},{"id":"12967","type":"Chemical","text":["maltolyl p-coumarate"],"offsets":[[260,280]],"normalized":[{"db_name":"MESH","db_id":"C524754"}]},{"id":"12968","type":"Chemical","text":["maltol"],"offsets":[[306,312]],"normalized":[{"db_name":"MESH","db_id":"C008316"}]},{"id":"12969","type":"Chemical","text":["p-coumaric acid"],"offsets":[[317,332]],"normalized":[{"db_name":"MESH","db_id":"C032171"}]},{"id":"12970","type":"Chemical","text":["maltolyl p-coumarate"],"offsets":[[380,400]],"normalized":[{"db_name":"MESH","db_id":"C524754"}]},{"id":"12971","type":"Disease","text":["cognitive decline"],"offsets":[[415,432]],"normalized":[{"db_name":"MESH","db_id":"D003072"}]},{"id":"12972","type":"Chemical","text":["scopolamine"],"offsets":[[436,447]],"normalized":[{"db_name":"MESH","db_id":"D012601"}]},{"id":"12973","type":"Chemical","text":["amyloid beta peptide(1-42)"],"offsets":[[469,495]],"normalized":[{"db_name":"MESH","db_id":"C544092"}]},{"id":"12974","type":"Chemical","text":["Maltolyl p-coumarate"],"offsets":[[510,530]],"normalized":[{"db_name":"MESH","db_id":"C524754"}]},{"id":"12975","type":"Disease","text":["cognitive deficits"],"offsets":[[554,572]],"normalized":[{"db_name":"MESH","db_id":"D003072"}]},{"id":"12976","type":"Chemical","text":["amyloid beta peptide(1-42)"],"offsets":[[691,717]],"normalized":[{"db_name":"MESH","db_id":"C544092"}]},{"id":"12977","type":"Chemical","text":["maltolyl p-coumarate"],"offsets":[[780,800]],"normalized":[{"db_name":"MESH","db_id":"C524754"}]},{"id":"12978","type":"Chemical","text":["maltolyl p-coumarate"],"offsets":[[858,878]],"normalized":[{"db_name":"MESH","db_id":"C524754"}]},{"id":"12979","type":"Chemical","text":["amyloid beta peptide(1-42)"],"offsets":[[898,924]],"normalized":[{"db_name":"MESH","db_id":"C544092"}]},{"id":"12980","type":"Chemical","text":["glutamate"],"offsets":[[926,935]],"normalized":[{"db_name":"MESH","db_id":"D018698"}]},{"id":"12981","type":"Chemical","text":["H2O2"],"offsets":[[939,943]],"normalized":[{"db_name":"MESH","db_id":"D006861"}]},{"id":"12982","type":"Chemical","text":["maltolyl p-coumarate"],"offsets":[[959,979]],"normalized":[{"db_name":"MESH","db_id":"C524754"}]},{"id":"12983","type":"Chemical","text":["maltolyl p-coumarate"],"offsets":[[1186,1206]],"normalized":[{"db_name":"MESH","db_id":"C524754"}]},{"id":"12984","type":"Disease","text":["Alzheimer's disease"],"offsets":[[1252,1271]],"normalized":[{"db_name":"MESH","db_id":"D000544"}]},{"id":"12985","type":"Disease","text":["neuronal death"],"offsets":[[1309,1323]],"normalized":[{"db_name":"MESH","db_id":"D009410"}]},{"id":"12986","type":"Disease","text":["decline of cognitive function"],"offsets":[[1340,1369]],"normalized":[{"db_name":"MESH","db_id":"D003072"}]}],"events":[],"coreferences":[],"relations":[{"id":"12987","type":"CID","arg1_id":"12972","arg2_id":"12965","normalized":[]},{"id":"12988","type":"CID","arg1_id":"12972","arg2_id":"12971","normalized":[]},{"id":"12989","type":"CID","arg1_id":"12972","arg2_id":"12975","normalized":[]},{"id":"12990","type":"CID","arg1_id":"12972","arg2_id":"12986","normalized":[]}]}
{"id":"12991","document_id":"17639754","passages":[{"id":"12992","type":"title","text":["Interaction between warfarin and levofloxacin: case series."],"offsets":[[0,59]]},{"id":"12993","type":"abstract","text":["Warfarin is the most widely used oral anticoagulant and is indicated for many clinical conditions. Levofloxacin, a fluoroquinolone, is one of the most commonly prescribed antibiotics in clinical practice and is effective against Gram-positive, Gram-negative, and atypical bacteria. While small prospective studies have not revealed any significant drug-drug interaction between warfarin and levofloxacin, several case reports have indicated that levofloxacin may significantly potentiate the anticoagulation effect of warfarin. We report 3 cases of serious bleeding complications that appear to be the result of the interaction between warfarin and levofloxacin. Physicians should be aware of this potential interaction and use caution when prescribing levofloxacin to patients taking warfarin."],"offsets":[[60,854]]}],"entities":[{"id":"12994","type":"Chemical","text":["warfarin"],"offsets":[[20,28]],"normalized":[{"db_name":"MESH","db_id":"D014859"}]},{"id":"12995","type":"Chemical","text":["levofloxacin"],"offsets":[[33,45]],"normalized":[{"db_name":"MESH","db_id":"D064704"}]},{"id":"12996","type":"Chemical","text":["Warfarin"],"offsets":[[60,68]],"normalized":[{"db_name":"MESH","db_id":"D014859"}]},{"id":"12997","type":"Chemical","text":["Levofloxacin"],"offsets":[[159,171]],"normalized":[{"db_name":"MESH","db_id":"D064704"}]},{"id":"12998","type":"Chemical","text":["fluoroquinolone"],"offsets":[[175,190]],"normalized":[{"db_name":"MESH","db_id":"D024841"}]},{"id":"12999","type":"Chemical","text":["warfarin"],"offsets":[[438,446]],"normalized":[{"db_name":"MESH","db_id":"D014859"}]},{"id":"13000","type":"Chemical","text":["levofloxacin"],"offsets":[[451,463]],"normalized":[{"db_name":"MESH","db_id":"D064704"}]},{"id":"13001","type":"Chemical","text":["levofloxacin"],"offsets":[[506,518]],"normalized":[{"db_name":"MESH","db_id":"D064704"}]},{"id":"13002","type":"Chemical","text":["warfarin"],"offsets":[[578,586]],"normalized":[{"db_name":"MESH","db_id":"D014859"}]},{"id":"13003","type":"Disease","text":["bleeding"],"offsets":[[617,625]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"13004","type":"Chemical","text":["warfarin"],"offsets":[[696,704]],"normalized":[{"db_name":"MESH","db_id":"D014859"}]},{"id":"13005","type":"Chemical","text":["levofloxacin"],"offsets":[[709,721]],"normalized":[{"db_name":"MESH","db_id":"D064704"}]},{"id":"13006","type":"Chemical","text":["levofloxacin"],"offsets":[[813,825]],"normalized":[{"db_name":"MESH","db_id":"D064704"}]},{"id":"13007","type":"Chemical","text":["warfarin"],"offsets":[[845,853]],"normalized":[{"db_name":"MESH","db_id":"D014859"}]}],"events":[],"coreferences":[],"relations":[{"id":"13008","type":"CID","arg1_id":"12994","arg2_id":"13003","normalized":[]},{"id":"13009","type":"CID","arg1_id":"12996","arg2_id":"13003","normalized":[]},{"id":"13010","type":"CID","arg1_id":"12999","arg2_id":"13003","normalized":[]},{"id":"13011","type":"CID","arg1_id":"13002","arg2_id":"13003","normalized":[]},{"id":"13012","type":"CID","arg1_id":"13004","arg2_id":"13003","normalized":[]},{"id":"13013","type":"CID","arg1_id":"13007","arg2_id":"13003","normalized":[]},{"id":"13014","type":"CID","arg1_id":"12995","arg2_id":"13003","normalized":[]},{"id":"13015","type":"CID","arg1_id":"12997","arg2_id":"13003","normalized":[]},{"id":"13016","type":"CID","arg1_id":"13000","arg2_id":"13003","normalized":[]},{"id":"13017","type":"CID","arg1_id":"13001","arg2_id":"13003","normalized":[]},{"id":"13018","type":"CID","arg1_id":"13005","arg2_id":"13003","normalized":[]},{"id":"13019","type":"CID","arg1_id":"13006","arg2_id":"13003","normalized":[]}]}
{"id":"13020","document_id":"17854040","passages":[{"id":"13021","type":"title","text":["Mutations associated with lamivudine-resistance in therapy-na  ve hepatitis B virus (HBV) infected patients with and without HIV co-infection: implications for antiretroviral therapy in HBV and HIV co-infected South African patients."],"offsets":[[0,233]]},{"id":"13022","type":"abstract","text":["This was an exploratory study to investigate lamivudine-resistant hepatitis B virus (HBV) strains in selected lamivudine-na  ve HBV carriers with and without human immunodeficiency virus (HIV) co-infection in South African patients. Thirty-five lamivudine-na  ve HBV infected patients with or without HIV co-infection were studied: 15 chronic HBV mono-infected patients and 20 HBV-HIV co-infected patients. The latter group was further sub-divided into 13 occult HBV (HBsAg-negative) and 7 overt HBV (HBsAg- positive) patients. HBsAg, anti-HBs, anti-HBc, and anti-HIV 1\/2 were determined as part of routine diagnosis using Axsym assays (Abbott Laboratories, North Chicago, IL). Serum samples were PCR amplified with HBV reverse transcriptase (RT) primers, followed by direct sequencing across the tyrosine-methionine-aspartate-aspartate (YMDD) motif of the major catalytic region in the C domain of the HBV RT enzyme. HBV viral load was performed with Amplicor HBV Monitor test v2.0 (Roche Diagnostics, Penzberg, Germany). HBV lamivudine-resistant strains were detected in 3 of 15 mono-infected chronic hepatitis B patients and 10 of 20 HBV-HIV co-infected patients. To the best of our knowledge, this constitutes the first report of HBV lamivudine-resistant strains in therapy-na  ve HBV-HIV co-infected patients. The HBV viral loads for mono-infected and co-infected patients ranged from 3.32 x 10(2) to 3.82 x 10(7) and <200 to 4.40 x 10(3) copies\/ml, respectively. It remains to be seen whether such pre-existing antiviral mutations could result in widespread emergence of HBV resistant strains when lamivudine-containing highly active antiretroviral (ARV) treatment (HAART) regimens become widely applied in South Africa, as this is likely to have potential implications in the management of HBV-HIV co-infected patients."],"offsets":[[234,2060]]}],"entities":[{"id":"13023","type":"Chemical","text":["lamivudine"],"offsets":[[26,36]],"normalized":[{"db_name":"MESH","db_id":"D019259"}]},{"id":"13024","type":"Chemical","text":["na"],"offsets":[[59,61]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"13025","type":"Disease","text":["hepatitis B virus (HBV) infected"],"offsets":[[66,98]],"normalized":[{"db_name":"MESH","db_id":"D006509"}]},{"id":"13026","type":"Disease","text":["HIV co-infection"],"offsets":[[125,141]],"normalized":[{"db_name":"MESH","db_id":"D015658"}]},{"id":"13027","type":"Disease","text":["HBV and HIV co-infected"],"offsets":[[186,209]],"normalized":[{"db_name":"MESH","db_id":"D006509"},{"db_name":"MESH","db_id":"D015658"}]},{"id":"13028","type":"Disease","text":["HBV","infected"],"offsets":[[186,189],[201,209]],"normalized":[{"db_name":"MESH","db_id":"D006509"}]},{"id":"13029","type":"Disease","text":["HIV","infected"],"offsets":[[194,197],[201,209]],"normalized":[{"db_name":"MESH","db_id":"D015658"}]},{"id":"13030","type":"Chemical","text":["lamivudine"],"offsets":[[279,289]],"normalized":[{"db_name":"MESH","db_id":"D019259"}]},{"id":"13031","type":"Disease","text":["hepatitis B"],"offsets":[[300,311]],"normalized":[{"db_name":"MESH","db_id":"D006509"}]},{"id":"13032","type":"Chemical","text":["lamivudine"],"offsets":[[344,354]],"normalized":[{"db_name":"MESH","db_id":"D019259"}]},{"id":"13033","type":"Chemical","text":["na"],"offsets":[[355,357]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"13034","type":"Disease","text":["human immunodeficiency virus (HIV) co-infection"],"offsets":[[392,439]],"normalized":[{"db_name":"MESH","db_id":"D015658"}]},{"id":"13035","type":"Chemical","text":["lamivudine"],"offsets":[[479,489]],"normalized":[{"db_name":"MESH","db_id":"D019259"}]},{"id":"13036","type":"Chemical","text":["na"],"offsets":[[490,492]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"13037","type":"Disease","text":["HBV infected"],"offsets":[[497,509]],"normalized":[{"db_name":"MESH","db_id":"D006509"}]},{"id":"13038","type":"Disease","text":["HIV co-infection"],"offsets":[[535,551]],"normalized":[{"db_name":"MESH","db_id":"D015658"}]},{"id":"13039","type":"Disease","text":["HBV mono-infected"],"offsets":[[577,594]],"normalized":[{"db_name":"MESH","db_id":"D006509"}]},{"id":"13040","type":"Disease","text":["HBV-HIV co-infected"],"offsets":[[611,630]],"normalized":[{"db_name":"MESH","db_id":"D006509"},{"db_name":"MESH","db_id":"D015658"}]},{"id":"13041","type":"Disease","text":["HBV","infected"],"offsets":[[611,614],[622,630]],"normalized":[{"db_name":"MESH","db_id":"D006509"}]},{"id":"13042","type":"Disease","text":["HIV","infected"],"offsets":[[615,618],[622,630]],"normalized":[{"db_name":"MESH","db_id":"D015658"}]},{"id":"13043","type":"Chemical","text":["HBsAg"],"offsets":[[702,707]],"normalized":[{"db_name":"MESH","db_id":"D006514"}]},{"id":"13044","type":"Chemical","text":["HBsAg"],"offsets":[[735,740]],"normalized":[{"db_name":"MESH","db_id":"D006514"}]},{"id":"13045","type":"Chemical","text":["HBsAg"],"offsets":[[762,767]],"normalized":[{"db_name":"MESH","db_id":"D006514"}]},{"id":"13046","type":"Chemical","text":["tyrosine"],"offsets":[[1031,1039]],"normalized":[{"db_name":"MESH","db_id":"D014443"}]},{"id":"13047","type":"Chemical","text":["methionine"],"offsets":[[1040,1050]],"normalized":[{"db_name":"MESH","db_id":"D008715"}]},{"id":"13048","type":"Chemical","text":["aspartate"],"offsets":[[1051,1060]],"normalized":[{"db_name":"MESH","db_id":"D001224"}]},{"id":"13049","type":"Chemical","text":["aspartate"],"offsets":[[1061,1070]],"normalized":[{"db_name":"MESH","db_id":"D001224"}]},{"id":"13050","type":"Chemical","text":["lamivudine"],"offsets":[[1261,1271]],"normalized":[{"db_name":"MESH","db_id":"D019259"}]},{"id":"13051","type":"Disease","text":["hepatitis B"],"offsets":[[1337,1348]],"normalized":[{"db_name":"MESH","db_id":"D006509"}]},{"id":"13052","type":"Disease","text":["HBV-HIV co-infected"],"offsets":[[1371,1390]],"normalized":[{"db_name":"MESH","db_id":"D006509"},{"db_name":"MESH","db_id":"D015658"}]},{"id":"13053","type":"Disease","text":["HBV","infected"],"offsets":[[1371,1374],[1382,1390]],"normalized":[{"db_name":"MESH","db_id":"D006509"}]},{"id":"13054","type":"Disease","text":["HIV","infected"],"offsets":[[1375,1378],[1382,1390]],"normalized":[{"db_name":"MESH","db_id":"D015658"}]},{"id":"13055","type":"Chemical","text":["lamivudine"],"offsets":[[1472,1482]],"normalized":[{"db_name":"MESH","db_id":"D019259"}]},{"id":"13056","type":"Chemical","text":["na"],"offsets":[[1512,1514]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"13057","type":"Disease","text":["HBV-HIV 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{"id":"13109","document_id":"18221780","passages":[{"id":"13110","type":"title","text":["Sex differences in NMDA antagonist enhancement of morphine antihyperalgesia in a capsaicin model of persistent pain: comparisons to two models of acute pain."],"offsets":[[0,157]]},{"id":"13111","type":"abstract","text":["In acute pain models, N-methyl-D-aspartate (NMDA) antagonists enhance the antinociceptive effects of morphine to a greater extent in males than females. The purpose of this investigation was to extend these findings to a persistent pain model which could be distinguished from acute pain models on the basis of the nociceptive fibers activated, neurochemical substrates, and duration of the nociceptive stimulus. To this end, persistent hyperalgesia was induced by administration of capsaicin in the tail of gonadally intact F344 rats, following which the tail was immersed in a mildly noxious thermal stimulus, and tail-withdrawal latencies measured. For comparison, tests were conducted in two acute pain models, the hotplate and warm water tail-withdrawal procedures. In males, the non-competitive NMDA antagonist dextromethorphan enhanced the antihyperalgesic effect of low to moderate doses of morphine in a dose-and time-dependent manner. Across the doses and pretreatment times examined, enhancement was not observed in females. Enhancement of morphine antinociception by dextromethorphan was seen in both males and females in the acute pain models, with the magnitude of this effect being greater in males. These findings demonstrate a sexually-dimorphic interaction between NMDA antagonists and morphine in a persistent pain model that can be distinguished from those observed in acute pain models."],"offsets":[[158,1565]]}],"entities":[{"id":"13112","type":"Chemical","text":["NMDA"],"offsets":[[19,23]],"normalized":[{"db_name":"MESH","db_id":"D016202"}]},{"id":"13113","type":"Chemical","text":["morphine"],"offsets":[[50,58]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"13114","type":"Chemical","text":["capsaicin"],"offsets":[[81,90]],"normalized":[{"db_name":"MESH","db_id":"D002211"}]},{"id":"13115","type":"Disease","text":["pain"],"offsets":[[111,115]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"13116","type":"Disease","text":["acute pain"],"offsets":[[146,156]],"normalized":[{"db_name":"MESH","db_id":"D059787"}]},{"id":"13117","type":"Disease","text":["acute pain"],"offsets":[[161,171]],"normalized":[{"db_name":"MESH","db_id":"D059787"}]},{"id":"13118","type":"Chemical","text":["N-methyl-D-aspartate"],"offsets":[[180,200]],"normalized":[{"db_name":"MESH","db_id":"D016202"}]},{"id":"13119","type":"Chemical","text":["NMDA"],"offsets":[[202,206]],"normalized":[{"db_name":"MESH","db_id":"D016202"}]},{"id":"13120","type":"Chemical","text":["morphine"],"offsets":[[259,267]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"13121","type":"Disease","text":["pain"],"offsets":[[390,394]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"13122","type":"Disease","text":["acute pain"],"offsets":[[435,445]],"normalized":[{"db_name":"MESH","db_id":"D059787"}]},{"id":"13123","type":"Disease","text":["hyperalgesia"],"offsets":[[595,607]],"normalized":[{"db_name":"MESH","db_id":"D006930"}]},{"id":"13124","type":"Chemical","text":["capsaicin"],"offsets":[[641,650]],"normalized":[{"db_name":"MESH","db_id":"D002211"}]},{"id":"13125","type":"Disease","text":["acute pain"],"offsets":[[854,864]],"normalized":[{"db_name":"MESH","db_id":"D059787"}]},{"id":"13126","type":"Chemical","text":["NMDA"],"offsets":[[959,963]],"normalized":[{"db_name":"MESH","db_id":"D016202"}]},{"id":"13127","type":"Chemical","text":["dextromethorphan"],"offsets":[[975,991]],"normalized":[{"db_name":"MESH","db_id":"D003915"}]},{"id":"13128","type":"Chemical","text":["morphine"],"offsets":[[1057,1065]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"13129","type":"Chemical","text":["morphine"],"offsets":[[1209,1217]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"13130","type":"Chemical","text":["dextromethorphan"],"offsets":[[1237,1253]],"normalized":[{"db_name":"MESH","db_id":"D003915"}]},{"id":"13131","type":"Disease","text":["acute pain"],"offsets":[[1296,1306]],"normalized":[{"db_name":"MESH","db_id":"D059787"}]},{"id":"13132","type":"Chemical","text":["NMDA"],"offsets":[[1441,1445]],"normalized":[{"db_name":"MESH","db_id":"D016202"}]},{"id":"13133","type":"Chemical","text":["morphine"],"offsets":[[1462,1470]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"13134","type":"Disease","text":["pain"],"offsets":[[1487,1491]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"13135","type":"Disease","text":["acute pain"],"offsets":[[1547,1557]],"normalized":[{"db_name":"MESH","db_id":"D059787"}]}],"events":[],"coreferences":[],"relations":[{"id":"13136","type":"CID","arg1_id":"13114","arg2_id":"13123","normalized":[]},{"id":"13137","type":"CID","arg1_id":"13124","arg2_id":"13123","normalized":[]}]}
{"id":"13138","document_id":"18261172","passages":[{"id":"13139","type":"title","text":["Development of proteinuria after switch to sirolimus-based immunosuppression in long-term cardiac transplant patients."],"offsets":[[0,118]]},{"id":"13140","type":"abstract","text":["Calcineurin-inhibitor therapy can lead to renal dysfunction in heart transplantation patients. The novel immunosuppressive (IS) drug sirolmus (Srl) lacks nephrotoxic effects; however, proteinuria associated with Srl has been reported following renal transplantation. In cardiac transplantation, the incidence of proteinuria associated with Srl is unknown. In this study, long-term cardiac transplant patients were switched from cyclosporine to Srl-based IS. Concomitant IS consisted of mycophenolate mofetil +\/- steroids. Proteinuria increased significantly from a median of 0.13 g\/day (range 0-5.7) preswitch to 0.23 g\/day (0-9.88) at 24 months postswitch (p = 0.0024). Before the switch, 11.5% of patients had high-grade proteinuria (>1.0 g\/day); this increased to 22.9% postswitch (p = 0.006). ACE inhibitor and angiotensin-releasing blocker (ARB) therapy reduced proteinuria development. Patients without proteinuria had increased renal function (median 42.5 vs. 64.1, p = 0.25), whereas patients who developed high-grade proteinuria showed decreased renal function at the end of follow-up (median 39.6 vs. 29.2, p = 0.125). Thus, proteinuria may develop in cardiac transplant patients after switch to Srl, which may have an adverse effect on renal function in these patients. Srl should be used with ACEi\/ARB therapy and patients monitored for proteinuria and increased renal dysfunction."],"offsets":[[119,1512]]}],"entities":[{"id":"13141","type":"Disease","text":["proteinuria"],"offsets":[[15,26]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]},{"id":"13142","type":"Chemical","text":["sirolimus"],"offsets":[[43,52]],"normalized":[{"db_name":"MESH","db_id":"D020123"}]},{"id":"13143","type":"Disease","text":["renal 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{"id":"13241","document_id":"18329269","passages":[{"id":"13242","type":"title","text":["Synthesis of N-pyrimidinyl-2-phenoxyacetamides as adenosine A2A receptor antagonists."],"offsets":[[0,85]]},{"id":"13243","type":"abstract","text":["A series of N-pyrimidinyl-2-phenoxyacetamide adenosine A(2A) antagonists is described. SAR studies led to compound 14 with excellent potency (K(i) = 0.4 nM), selectivity (A(1)\/A(2A) > 100), and efficacy (MED 10 mg\/kg p.o.) in the rat haloperidol-induced catalepsy model for Parkinson's disease."],"offsets":[[86,380]]}],"entities":[{"id":"13244","type":"Chemical","text":["N-pyrimidinyl-2-phenoxyacetamides"],"offsets":[[13,46]],"normalized":[{"db_name":"MESH","db_id":"D010642"}]},{"id":"13245","type":"Chemical","text":["adenosine"],"offsets":[[50,59]],"normalized":[{"db_name":"MESH","db_id":"D000241"}]},{"id":"13246","type":"Chemical","text":["N-pyrimidinyl-2-phenoxyacetamide"],"offsets":[[98,130]],"normalized":[{"db_name":"MESH","db_id":"D010642"}]},{"id":"13247","type":"Chemical","text":["adenosine"],"offsets":[[131,140]],"normalized":[{"db_name":"MESH","db_id":"D000241"}]},{"id":"13248","type":"Chemical","text":["haloperidol"],"offsets":[[320,331]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"13249","type":"Disease","text":["catalepsy"],"offsets":[[340,349]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"13250","type":"Disease","text":["Parkinson's disease"],"offsets":[[360,379]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]}],"events":[],"coreferences":[],"relations":[{"id":"13251","type":"CID","arg1_id":"13248","arg2_id":"13249","normalized":[]}]}
{"id":"13252","document_id":"18410508","passages":[{"id":"13253","type":"title","text":["Methamphetamine-induced neurotoxicity and microglial activation are not mediated by fractalkine receptor signaling."],"offsets":[[0,115]]},{"id":"13254","type":"abstract","text":["Methamphetamine (METH) damages dopamine (DA) nerve endings by a process that has been linked to microglial activation but the signaling pathways that mediate this response have not yet been delineated. Cardona et al. [Nat. Neurosci. 9 (2006), 917] recently identified the microglial-specific fractalkine receptor (CX3CR1) as an important mediator of MPTP-induced neurodegeneration of DA neurons. Because the CNS damage caused by METH and MPTP is highly selective for the DA neuronal system in mouse models of neurotoxicity, we hypothesized that the CX3CR1 plays a role in METH-induced neurotoxicity and microglial activation. Mice in which the CX3CR1 gene has been deleted and replaced with a cDNA encoding enhanced green fluorescent protein (eGFP) were treated with METH and examined for striatal neurotoxicity. METH depleted DA, caused microglial activation, and increased body temperature in CX3CR1 knockout mice to the same extent and over the same time course seen in wild-type controls. The effects of METH in CX3CR1 knockout mice were not gender-dependent and did not extend beyond the striatum. Striatal microglia expressing eGFP constitutively show morphological changes after METH that are characteristic of activation. This response was restricted to the striatum and contrasted sharply with unresponsive eGFP-microglia in surrounding brain areas that are not damaged by METH. We conclude from these studies that CX3CR1 signaling does not modulate METH neurotoxicity or microglial activation. Furthermore, it appears that striatal-resident microglia respond to METH with an activation cascade and then return to a surveying state without undergoing apoptosis or migration."],"offsets":[[116,1799]]}],"entities":[{"id":"13255","type":"Chemical","text":["Methamphetamine"],"offsets":[[0,15]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"13256","type":"Disease","text":["neurotoxicity"],"offsets":[[24,37]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"13257","type":"Chemical","text":["Methamphetamine"],"offsets":[[116,131]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"13258","type":"Chemical","text":["METH"],"offsets":[[133,137]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"13259","type":"Chemical","text":["dopamine"],"offsets":[[147,155]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"13260","type":"Chemical","text":["DA"],"offsets":[[157,159]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"13261","type":"Chemical","text":["MPTP"],"offsets":[[466,470]],"normalized":[{"db_name":"MESH","db_id":"D015632"}]},{"id":"13262","type":"Disease","text":["neurodegeneration"],"offsets":[[479,496]],"normalized":[{"db_name":"MESH","db_id":"D009422"}]},{"id":"13263","type":"Chemical","text":["DA"],"offsets":[[500,502]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"13264","type":"Disease","text":["CNS damage"],"offsets":[[524,534]],"normalized":[{"db_name":"MESH","db_id":"D009422"}]},{"id":"13265","type":"Chemical","text":["METH"],"offsets":[[545,549]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"13266","type":"Chemical","text":["MPTP"],"offsets":[[554,558]],"normalized":[{"db_name":"MESH","db_id":"D015632"}]},{"id":"13267","type":"Chemical","text":["DA"],"offsets":[[587,589]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"13268","type":"Disease","text":["neurotoxicity"],"offsets":[[625,638]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"13269","type":"Chemical","text":["METH"],"offsets":[[688,692]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"13270","type":"Disease","text":["neurotoxicity"],"offsets":[[701,714]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"13271","type":"Chemical","text":["METH"],"offsets":[[883,887]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"13272","type":"Disease","text":["neurotoxicity"],"offsets":[[914,927]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"13273","type":"Chemical","text":["METH"],"offsets":[[929,933]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"13274","type":"Chemical","text":["DA"],"offsets":[[943,945]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"13275","type":"Chemical","text":["METH"],"offsets":[[1124,1128]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"13276","type":"Chemical","text":["METH"],"offsets":[[1302,1306]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"13277","type":"Chemical","text":["METH"],"offsets":[[1498,1502]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"13278","type":"Chemical","text":["METH"],"offsets":[[1575,1579]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"13279","type":"Disease","text":["neurotoxicity"],"offsets":[[1580,1593]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"13280","type":"Chemical","text":["METH"],"offsets":[[1688,1692]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]}],"events":[],"coreferences":[],"relations":[{"id":"13281","type":"CID","arg1_id":"13255","arg2_id":"13262","normalized":[]},{"id":"13282","type":"CID","arg1_id":"13255","arg2_id":"13264","normalized":[]},{"id":"13283","type":"CID","arg1_id":"13257","arg2_id":"13262","normalized":[]},{"id":"13284","type":"CID","arg1_id":"13257","arg2_id":"13264","normalized":[]},{"id":"13285","type":"CID","arg1_id":"13258","arg2_id":"13262","normalized":[]},{"id":"13286","type":"CID","arg1_id":"13258","arg2_id":"13264","normalized":[]},{"id":"13287","type":"CID","arg1_id":"13265","arg2_id":"13262","normalized":[]},{"id":"13288","type":"CID","arg1_id":"13265","arg2_id":"13264","normalized":[]},{"id":"13289","type":"CID","arg1_id":"13269","arg2_id":"13262","normalized":[]},{"id":"13290","type":"CID","arg1_id":"13269","arg2_id":"13264","normalized":[]},{"id":"13291","type":"CID","arg1_id":"13271","arg2_id":"13262","normalized":[]},{"id":"13292","type":"CID","arg1_id":"13271","arg2_id":"13264","normalized":[]},{"id":"13293","type":"CID","arg1_id":"13273","arg2_id":"13262","normalized":[]},{"id":"13294","type":"CID","arg1_id":"13273","arg2_id":"13264","normalized":[]},{"id":"13295","type":"CID","arg1_id":"13275","arg2_id":"13262","normalized":[]},{"id":"13296","type":"CID","arg1_id":"13275","arg2_id":"13264","normalized":[]},{"id":"13297","type":"CID","arg1_id":"13276","arg2_id":"13262","normalized":[]},{"id":"13298","type":"CID","arg1_id":"13276","arg2_id":"13264","normalized":[]},{"id":"13299","type":"CID","arg1_id":"13277","arg2_id":"13262","normalized":[]},{"id":"13300","type":"CID","arg1_id":"13277","arg2_id":"13264","normalized":[]},{"id":"13301","type":"CID","arg1_id":"13278","arg2_id":"13262","normalized":[]},{"id":"13302","type":"CID","arg1_id":"13278","arg2_id":"13264","normalized":[]},{"id":"13303","type":"CID","arg1_id":"13280","arg2_id":"13262","normalized":[]},{"id":"13304","type":"CID","arg1_id":"13280","arg2_id":"13264","normalized":[]},{"id":"13305","type":"CID","arg1_id":"13261","arg2_id":"13262","normalized":[]},{"id":"13306","type":"CID","arg1_id":"13261","arg2_id":"13264","normalized":[]},{"id":"13307","type":"CID","arg1_id":"13266","arg2_id":"13262","normalized":[]},{"id":"13308","type":"CID","arg1_id":"13266","arg2_id":"13264","normalized":[]}]}
{"id":"13309","document_id":"18503483","passages":[{"id":"13310","type":"title","text":["Recovery of tacrolimus-associated brachial neuritis after conversion to everolimus in a pediatric renal transplant recipient--case report and review of the literature."],"offsets":[[0,167]]},{"id":"13311","type":"abstract","text":["TAC has been shown to be a potent immunosuppressive agent for solid organ transplantation in pediatrics. Neurotoxicity is a potentially serious toxic effect. It is characterized by encephalopathy, headaches, seizures, or neurological deficits. Here, we describe an eight-and-a-half-yr-old male renal transplant recipient with right BN. MRI demonstrated hyperintense T2 signals in the cervical cord and right brachial plexus roots indicative of both myelitis and right brachial plexitis. Symptoms persisted for three months despite TAC dose reduction, administration of IVIG and four doses of methylprednisolone pulse therapy. Improvement and eventually full recovery only occurred after TAC was completely discontinued and successfully replaced by everolimus."],"offsets":[[168,927]]}],"entities":[{"id":"13312","type":"Chemical","text":["tacrolimus"],"offsets":[[12,22]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"13313","type":"Disease","text":["brachial neuritis"],"offsets":[[34,51]],"normalized":[{"db_name":"MESH","db_id":"D020968"}]},{"id":"13314","type":"Chemical","text":["everolimus"],"offsets":[[72,82]],"normalized":[{"db_name":"MESH","db_id":"C107135"}]},{"id":"13315","type":"Chemical","text":["TAC"],"offsets":[[168,171]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"13316","type":"Disease","text":["Neurotoxicity"],"offsets":[[273,286]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"13317","type":"Disease","text":["encephalopathy"],"offsets":[[349,363]],"normalized":[{"db_name":"MESH","db_id":"D001927"}]},{"id":"13318","type":"Disease","text":["headaches"],"offsets":[[365,374]],"normalized":[{"db_name":"MESH","db_id":"D006261"}]},{"id":"13319","type":"Disease","text":["seizures"],"offsets":[[376,384]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"13320","type":"Disease","text":["neurological deficits"],"offsets":[[389,410]],"normalized":[{"db_name":"MESH","db_id":"D009461"}]},{"id":"13321","type":"Disease","text":["myelitis"],"offsets":[[617,625]],"normalized":[{"db_name":"MESH","db_id":"D009187"}]},{"id":"13322","type":"Disease","text":["brachial plexitis"],"offsets":[[636,653]],"normalized":[{"db_name":"MESH","db_id":"D020968"}]},{"id":"13323","type":"Chemical","text":["TAC"],"offsets":[[699,702]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"13324","type":"Chemical","text":["methylprednisolone"],"offsets":[[760,778]],"normalized":[{"db_name":"MESH","db_id":"D008775"}]},{"id":"13325","type":"Chemical","text":["TAC"],"offsets":[[855,858]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"13326","type":"Chemical","text":["everolimus"],"offsets":[[916,926]],"normalized":[{"db_name":"MESH","db_id":"C107135"}]}],"events":[],"coreferences":[],"relations":[{"id":"13327","type":"CID","arg1_id":"13312","arg2_id":"13313","normalized":[]},{"id":"13328","type":"CID","arg1_id":"13312","arg2_id":"13322","normalized":[]},{"id":"13329","type":"CID","arg1_id":"13315","arg2_id":"13313","normalized":[]},{"id":"13330","type":"CID","arg1_id":"13315","arg2_id":"13322","normalized":[]},{"id":"13331","type":"CID","arg1_id":"13323","arg2_id":"13313","normalized":[]},{"id":"13332","type":"CID","arg1_id":"13323","arg2_id":"13322","normalized":[]},{"id":"13333","type":"CID","arg1_id":"13325","arg2_id":"13313","normalized":[]},{"id":"13334","type":"CID","arg1_id":"13325","arg2_id":"13322","normalized":[]}]}
{"id":"13335","document_id":"18560792","passages":[{"id":"13336","type":"title","text":["Valvular heart disease in patients with Parkinson's disease treated with pergolide. Course following treatment modifications."],"offsets":[[0,125]]},{"id":"13337","type":"abstract","text":["Valvular heart abnormalities have been reported in patients with Parkinson's disease (PD) treated with pergolide. However, the incidence and severity of these abnormalities vary from study to study and their course after drug withdrawal has not been systematically assessed. OBJECTIVES: To estimate the frequency and severity of valvular heart abnormality and its possible reversibility after drug withdrawal in a case-control study. METHODS: All PD patients in the Amiens area treated with pergolide were invited to attend a cardiologic assessment including transthoracic echocardiography. Thirty PD patients participated in the study. A second echocardiography was performed (median interval: 13 months) after pergolide withdrawal (n=10 patients). Controls were age- and sex-matched non-PD patients referred to the cardiology department. RESULTS: Compared to controls, aortic regurgitation (OR: 3.1; 95% IC: 1.1-8.8) and mitral regurgitation (OR: 10.7; 95% IC: 2.1-53) were more frequent in PD patients (tricuspid: NS). The number of affected valves (n=2.4+\/-0.7) and the sum of regurgitation grades (n=2.8+\/-1.09) were higher (p=0.008 and p=0.006, respectively) in the pergolide group. Severity of regurgitation was not correlated with pergolide cumulative dose. A restrictive pattern of valvular regurgitation, suggestive of the role of pergolide, was observed in 12\/30 (40%) patients including two with heart failure. Pergolide was discontinued in 10 patients with valvular heart disease, resulting in a lower regurgitation grade (p=0.01) at the second transthoracic echocardiography and the two patients with heart failure returned to nearly normal clinical examination. This study supports the high frequency of restrictive valve regurgitation in PD patients treated with pergolide and reveals that a significant improvement is usual when the treatment is converted to non-ergot dopamine agonists."],"offsets":[[126,2030]]}],"entities":[{"id":"13338","type":"Disease","text":["Valvular heart disease"],"offsets":[[0,22]],"normalized":[{"db_name":"MESH","db_id":"D006349"}]},{"id":"13339","type":"Disease","text":["Parkinson's disease"],"offsets":[[40,59]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"13340","type":"Chemical","text":["pergolide"],"offsets":[[73,82]],"normalized":[{"db_name":"MESH","db_id":"D010479"}]},{"id":"13341","type":"Disease","text":["Valvular heart abnormalities"],"offsets":[[126,154]],"normalized":[{"db_name":"MESH","db_id":"D006349"}]},{"id":"13342","type":"Disease","text":["Parkinson's disease"],"offsets":[[191,210]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"13343","type":"Disease","text":["PD"],"offsets":[[212,214]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"13344","type":"Chemical","text":["pergolide"],"offsets":[[229,238]],"normalized":[{"db_name":"MESH","db_id":"D010479"}]},{"id":"13345","type":"Disease","text":["valvular heart abnormality"],"offsets":[[455,481]],"normalized":[{"db_name":"MESH","db_id":"D006349"}]},{"id":"13346","type":"Disease","text":["PD"],"offsets":[[573,575]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"13347","type":"Chemical","text":["pergolide"],"offsets":[[617,626]],"normalized":[{"db_name":"MESH","db_id":"D010479"}]},{"id":"13348","type":"Disease","text":["PD"],"offsets":[[724,726]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"13349","type":"Chemical","text":["pergolide"],"offsets":[[838,847]],"normalized":[{"db_name":"MESH","db_id":"D010479"}]},{"id":"13350","type":"Disease","text":["PD"],"offsets":[[915,917]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"13351","type":"Disease","text":["aortic regurgitation"],"offsets":[[997,1017]],"normalized":[{"db_name":"MESH","db_id":"D001022"}]},{"id":"13352","type":"Disease","text":["mitral regurgitation"],"offsets":[[1049,1069]],"normalized":[{"db_name":"MESH","db_id":"D008944"}]},{"id":"13353","type":"Disease","text":["PD"],"offsets":[[1119,1121]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"13354","type":"Chemical","text":["pergolide"],"offsets":[[1298,1307]],"normalized":[{"db_name":"MESH","db_id":"D010479"}]},{"id":"13355","type":"Chemical","text":["pergolide"],"offsets":[[1365,1374]],"normalized":[{"db_name":"MESH","db_id":"D010479"}]},{"id":"13356","type":"Disease","text":["valvular regurgitation"],"offsets":[[1417,1439]],"normalized":[{"db_name":"MESH","db_id":"D006349"}]},{"id":"13357","type":"Chemical","text":["pergolide"],"offsets":[[1467,1476]],"normalized":[{"db_name":"MESH","db_id":"D010479"}]},{"id":"13358","type":"Disease","text":["heart failure"],"offsets":[[1534,1547]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]},{"id":"13359","type":"Chemical","text":["Pergolide"],"offsets":[[1549,1558]],"normalized":[{"db_name":"MESH","db_id":"D010479"}]},{"id":"13360","type":"Disease","text":["valvular heart disease"],"offsets":[[1596,1618]],"normalized":[{"db_name":"MESH","db_id":"D006349"}]},{"id":"13361","type":"Disease","text":["heart failure"],"offsets":[[1741,1754]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]},{"id":"13362","type":"Disease","text":["valve regurgitation"],"offsets":[[1857,1876]],"normalized":[{"db_name":"MESH","db_id":"D006349"}]},{"id":"13363","type":"Disease","text":["PD"],"offsets":[[1880,1882]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"13364","type":"Chemical","text":["pergolide"],"offsets":[[1905,1914]],"normalized":[{"db_name":"MESH","db_id":"D010479"}]},{"id":"13365","type":"Chemical","text":["dopamine"],"offsets":[[2012,2020]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]}],"events":[],"coreferences":[],"relations":[{"id":"13366","type":"CID","arg1_id":"13340","arg2_id":"13351","normalized":[]},{"id":"13367","type":"CID","arg1_id":"13344","arg2_id":"13351","normalized":[]},{"id":"13368","type":"CID","arg1_id":"13347","arg2_id":"13351","normalized":[]},{"id":"13369","type":"CID","arg1_id":"13349","arg2_id":"13351","normalized":[]},{"id":"13370","type":"CID","arg1_id":"13354","arg2_id":"13351","normalized":[]},{"id":"13371","type":"CID","arg1_id":"13355","arg2_id":"13351","normalized":[]},{"id":"13372","type":"CID","arg1_id":"13357","arg2_id":"13351","normalized":[]},{"id":"13373","type":"CID","arg1_id":"13359","arg2_id":"13351","normalized":[]},{"id":"13374","type":"CID","arg1_id":"13364","arg2_id":"13351","normalized":[]},{"id":"13375","type":"CID","arg1_id":"13340","arg2_id":"13352","normalized":[]},{"id":"13376","type":"CID","arg1_id":"13344","arg2_id":"13352","normalized":[]},{"id":"13377","type":"CID","arg1_id":"13347","arg2_id":"13352","normalized":[]},{"id":"13378","type":"CID","arg1_id":"13349","arg2_id":"13352","normalized":[]},{"id":"13379","type":"CID","arg1_id":"13354","arg2_id":"13352","normalized":[]},{"id":"13380","type":"CID","arg1_id":"13355","arg2_id":"13352","normalized":[]},{"id":"13381","type":"CID","arg1_id":"13357","arg2_id":"13352","normalized":[]},{"id":"13382","type":"CID","arg1_id":"13359","arg2_id":"13352","normalized":[]},{"id":"13383","type":"CID","arg1_id":"13364","arg2_id":"13352","normalized":[]}]}
{"id":"13384","document_id":"18726058","passages":[{"id":"13385","type":"title","text":["Adverse effects of topical papaverine on auditory nerve function."],"offsets":[[0,65]]},{"id":"13386","type":"abstract","text":["BACKGROUND: Papaverine hydrochloride is a direct-acting vasodilator used to manage vasospasm during various neurosurgical operations. Transient cranial nerve dysfunction has been described in a few cases with topical papaverine. This study supports previous reports and provides neurophysiological evidence of an adverse effect on the auditory nerve. METHODS: We conducted a retrospective review of 70 consecutive microvascular decompression operations and studied those patients who received topical papaverine for vasospasm. Topical papaverine was used as a direct therapeutic action to manage vasospasm in a total of 11 patients. The timing of papaverine application and ongoing operative events was reviewed relative to changes in neurophysiological recordings. Brainstem auditory evoked potentials (BAEPs) were routinely used to monitor cochlear nerve function during these operations. FINDINGS: A temporal relationship was found between topical papaverine and BAEP changes leading to complete waveform loss. The average temporal delay between papaverine and the onset of an adverse BAEP change was 5 min. In 10 of 11 patients, BAEP waves II\/III-V completely disappeared within 2 to 25 min after papaverine. Eight of these 10 patients had complete loss of BAEP waveforms within 10 min. One patient showed no recovery of later waves and a delayed profound sensorineural hearing loss. The average recovery time of BAEP waveforms to pre-papaverine baseline values was 39 min. CONCLUSIONS: Topical papaverine for the treatment of vasospasm was associated with the onset of a transient disturbance in neurophysiological function of the ascending auditory brainstem pathway. The complete disappearance of BAEP waveforms with a consistent temporal delay suggests a possible adverse effect on the proximal eighth nerve. Recommendations to avoid potential cranial nerve deficits from papaverine are provided."],"offsets":[[66,1970]]}],"entities":[{"id":"13387","type":"Chemical","text":["papaverine"],"offsets":[[27,37]],"normalized":[{"db_name":"MESH","db_id":"D010208"}]},{"id":"13388","type":"Chemical","text":["Papaverine hydrochloride"],"offsets":[[78,102]],"normalized":[{"db_name":"MESH","db_id":"D010208"}]},{"id":"13389","type":"Disease","text":["vasospasm"],"offsets":[[149,158]],"normalized":[{"db_name":"MESH","db_id":"D020301"}]},{"id":"13390","type":"Disease","text":["cranial nerve dysfunction"],"offsets":[[210,235]],"normalized":[{"db_name":"MESH","db_id":"D003389"}]},{"id":"13391","type":"Chemical","text":["papaverine"],"offsets":[[283,293]],"normalized":[{"db_name":"MESH","db_id":"D010208"}]},{"id":"13392","type":"Chemical","text":["papaverine"],"offsets":[[567,577]],"normalized":[{"db_name":"MESH","db_id":"D010208"}]},{"id":"13393","type":"Disease","text":["vasospasm"],"offsets":[[582,591]],"normalized":[{"db_name":"MESH","db_id":"D020301"}]},{"id":"13394","type":"Chemical","text":["papaverine"],"offsets":[[601,611]],"normalized":[{"db_name":"MESH","db_id":"D010208"}]},{"id":"13395","type":"Disease","text":["vasospasm"],"offsets":[[662,671]],"normalized":[{"db_name":"MESH","db_id":"D020301"}]},{"id":"13396","type":"Chemical","text":["papaverine"],"offsets":[[713,723]],"normalized":[{"db_name":"MESH","db_id":"D010208"}]},{"id":"13397","type":"Chemical","text":["papaverine"],"offsets":[[1017,1027]],"normalized":[{"db_name":"MESH","db_id":"D010208"}]},{"id":"13398","type":"Chemical","text":["papaverine"],"offsets":[[1115,1125]],"normalized":[{"db_name":"MESH","db_id":"D010208"}]},{"id":"13399","type":"Chemical","text":["papaverine"],"offsets":[[1267,1277]],"normalized":[{"db_name":"MESH","db_id":"D010208"}]},{"id":"13400","type":"Disease","text":["sensorineural hearing loss"],"offsets":[[1426,1452]],"normalized":[{"db_name":"MESH","db_id":"D006319"}]},{"id":"13401","type":"Chemical","text":["papaverine"],"offsets":[[1505,1515]],"normalized":[{"db_name":"MESH","db_id":"D010208"}]},{"id":"13402","type":"Chemical","text":["papaverine"],"offsets":[[1565,1575]],"normalized":[{"db_name":"MESH","db_id":"D010208"}]},{"id":"13403","type":"Disease","text":["vasospasm"],"offsets":[[1597,1606]],"normalized":[{"db_name":"MESH","db_id":"D020301"}]},{"id":"13404","type":"Disease","text":["adverse effect on the proximal eighth nerve"],"offsets":[[1838,1881]],"normalized":[{"db_name":"MESH","db_id":"D000160"}]},{"id":"13405","type":"Disease","text":["cranial nerve deficits"],"offsets":[[1918,1940]],"normalized":[{"db_name":"MESH","db_id":"D003389"}]},{"id":"13406","type":"Chemical","text":["papaverine"],"offsets":[[1946,1956]],"normalized":[{"db_name":"MESH","db_id":"D010208"}]}],"events":[],"coreferences":[],"relations":[{"id":"13407","type":"CID","arg1_id":"13387","arg2_id":"13404","normalized":[]},{"id":"13408","type":"CID","arg1_id":"13388","arg2_id":"13404","normalized":[]},{"id":"13409","type":"CID","arg1_id":"13391","arg2_id":"13404","normalized":[]},{"id":"13410","type":"CID","arg1_id":"13392","arg2_id":"13404","normalized":[]},{"id":"13411","type":"CID","arg1_id":"13394","arg2_id":"13404","normalized":[]},{"id":"13412","type":"CID","arg1_id":"13396","arg2_id":"13404","normalized":[]},{"id":"13413","type":"CID","arg1_id":"13397","arg2_id":"13404","normalized":[]},{"id":"13414","type":"CID","arg1_id":"13398","arg2_id":"13404","normalized":[]},{"id":"13415","type":"CID","arg1_id":"13399","arg2_id":"13404","normalized":[]},{"id":"13416","type":"CID","arg1_id":"13401","arg2_id":"13404","normalized":[]},{"id":"13417","type":"CID","arg1_id":"13402","arg2_id":"13404","normalized":[]},{"id":"13418","type":"CID","arg1_id":"13406","arg2_id":"13404","normalized":[]},{"id":"13419","type":"CID","arg1_id":"13387","arg2_id":"13400","normalized":[]},{"id":"13420","type":"CID","arg1_id":"13388","arg2_id":"13400","normalized":[]},{"id":"13421","type":"CID","arg1_id":"13391","arg2_id":"13400","normalized":[]},{"id":"13422","type":"CID","arg1_id":"13392","arg2_id":"13400","normalized":[]},{"id":"13423","type":"CID","arg1_id":"13394","arg2_id":"13400","normalized":[]},{"id":"13424","type":"CID","arg1_id":"13396","arg2_id":"13400","normalized":[]},{"id":"13425","type":"CID","arg1_id":"13397","arg2_id":"13400","normalized":[]},{"id":"13426","type":"CID","arg1_id":"13398","arg2_id":"13400","normalized":[]},{"id":"13427","type":"CID","arg1_id":"13399","arg2_id":"13400","normalized":[]},{"id":"13428","type":"CID","arg1_id":"13401","arg2_id":"13400","normalized":[]},{"id":"13429","type":"CID","arg1_id":"13402","arg2_id":"13400","normalized":[]},{"id":"13430","type":"CID","arg1_id":"13406","arg2_id":"13400","normalized":[]}]}
{"id":"13431","document_id":"18754075","passages":[{"id":"13432","type":"title","text":["Massive proteinuria and acute renal failure after oral bisphosphonate (alendronate) administration in a patient with focal segmental glomerulosclerosis."],"offsets":[[0,152]]},{"id":"13433","type":"abstract","text":["A 61-year-old Japanese man with nephrotic syndrome due to focal segmental glomerulosclerosis was initially responding well to steroid therapy. The amount of daily urinary protein decreased from 15.6 to 2.8 g. Within 14 days of the oral bisphosphonate (alendronate sodium) administration, the amount of daily urinary protein increased rapidly up to 12.8 g with acute renal failure. After discontinuing the oral alendronate, the patient underwent six cycles of hemodialysis and four cycles of LDL apheresis. Urinary volume and serum creatinine levels recovered to the normal range, with urinary protein disappearing completely within 40 days. This report demonstrates that not only intravenous, but also oral bisphosphonates can aggravate proteinuria and acute renal failure."],"offsets":[[153,926]]}],"entities":[{"id":"13434","type":"Disease","text":["proteinuria"],"offsets":[[8,19]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]},{"id":"13435","type":"Disease","text":["acute renal failure"],"offsets":[[24,43]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"13436","type":"Chemical","text":["bisphosphonate"],"offsets":[[55,69]],"normalized":[{"db_name":"MESH","db_id":"D004164"}]},{"id":"13437","type":"Chemical","text":["alendronate"],"offsets":[[71,82]],"normalized":[{"db_name":"MESH","db_id":"D019386"}]},{"id":"13438","type":"Disease","text":["focal segmental glomerulosclerosis"],"offsets":[[117,151]],"normalized":[{"db_name":"MESH","db_id":"D005923"}]},{"id":"13439","type":"Disease","text":["nephrotic syndrome"],"offsets":[[185,203]],"normalized":[{"db_name":"MESH","db_id":"D009404"}]},{"id":"13440","type":"Disease","text":["focal segmental glomerulosclerosis"],"offsets":[[211,245]],"normalized":[{"db_name":"MESH","db_id":"D005923"}]},{"id":"13441","type":"Chemical","text":["steroid"],"offsets":[[279,286]],"normalized":[{"db_name":"MESH","db_id":"D013256"}]},{"id":"13442","type":"Chemical","text":["bisphosphonate"],"offsets":[[389,403]],"normalized":[{"db_name":"MESH","db_id":"D004164"}]},{"id":"13443","type":"Chemical","text":["alendronate sodium"],"offsets":[[405,423]],"normalized":[{"db_name":"MESH","db_id":"D019386"}]},{"id":"13444","type":"Disease","text":["acute renal failure"],"offsets":[[513,532]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"13445","type":"Chemical","text":["alendronate"],"offsets":[[563,574]],"normalized":[{"db_name":"MESH","db_id":"D019386"}]},{"id":"13446","type":"Chemical","text":["creatinine"],"offsets":[[684,694]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"13447","type":"Chemical","text":["bisphosphonates"],"offsets":[[860,875]],"normalized":[{"db_name":"MESH","db_id":"D004164"}]},{"id":"13448","type":"Disease","text":["proteinuria"],"offsets":[[890,901]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]},{"id":"13449","type":"Disease","text":["acute renal failure"],"offsets":[[906,925]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]}],"events":[],"coreferences":[],"relations":[{"id":"13450","type":"CID","arg1_id":"13437","arg2_id":"13435","normalized":[]},{"id":"13451","type":"CID","arg1_id":"13437","arg2_id":"13444","normalized":[]},{"id":"13452","type":"CID","arg1_id":"13437","arg2_id":"13449","normalized":[]},{"id":"13453","type":"CID","arg1_id":"13443","arg2_id":"13435","normalized":[]},{"id":"13454","type":"CID","arg1_id":"13443","arg2_id":"13444","normalized":[]},{"id":"13455","type":"CID","arg1_id":"13443","arg2_id":"13449","normalized":[]},{"id":"13456","type":"CID","arg1_id":"13445","arg2_id":"13435","normalized":[]},{"id":"13457","type":"CID","arg1_id":"13445","arg2_id":"13444","normalized":[]},{"id":"13458","type":"CID","arg1_id":"13445","arg2_id":"13449","normalized":[]},{"id":"13459","type":"CID","arg1_id":"13437","arg2_id":"13434","normalized":[]},{"id":"13460","type":"CID","arg1_id":"13437","arg2_id":"13448","normalized":[]},{"id":"13461","type":"CID","arg1_id":"13443","arg2_id":"13434","normalized":[]},{"id":"13462","type":"CID","arg1_id":"13443","arg2_id":"13448","normalized":[]},{"id":"13463","type":"CID","arg1_id":"13445","arg2_id":"13434","normalized":[]},{"id":"13464","type":"CID","arg1_id":"13445","arg2_id":"13448","normalized":[]}]}
{"id":"13465","document_id":"18768591","passages":[{"id":"13466","type":"title","text":["Serum- and glucocorticoid-inducible kinase 1 in doxorubicin-induced nephrotic syndrome."],"offsets":[[0,87]]},{"id":"13467","type":"abstract","text":["Doxorubicin-induced nephropathy leads to epithelial sodium channel (ENaC)-dependent volume retention and renal fibrosis. The aldosterone-sensitive serum- and glucocorticoid-inducible kinase SGK1 has been shown to participate in the stimulation of ENaC and to mediate renal fibrosis following mineralocorticoid and salt excess. The present study was performed to elucidate the role of SGK1 in the volume retention and fibrosis during nephrotic syndrome. To this end, doxorubicin (15 mug\/g body wt) was injected intravenously into gene-targeted mice lacking SGK1 (sgk1(-\/-)) and their wild-type littermates (sgk1(+\/+)). Doxorubicin treatment resulted in heavy proteinuria (>100 mg protein\/mg crea) in 15\/44 of sgk1(+\/+) and 15\/44 of sgk1(-\/-) mice leading to severe nephrotic syndrome with ascites, lipidemia, and hypoalbuminemia in both genotypes. Plasma aldosterone levels increased in nephrotic mice of both genotypes and was followed by increased SGK1 protein expression in sgk1(+\/+) mice. Urinary sodium excretion reached signficantly lower values in sgk1(+\/+) mice (15 +\/- 5 mumol\/mg crea) than in sgk1(-\/-) mice (35 +\/- 5 mumol\/mg crea) and was associated with a significantly higher body weight gain in sgk1(+\/+) compared with sgk1(-\/-) mice (+6.6 +\/- 0.7 vs. +4.1 +\/- 0.8 g). During the course of nephrotic syndrome, serum urea concentrations increased significantly faster in sgk1(-\/-) mice than in sgk1(+\/+) mice leading to uremia and a reduced median survival in sgk1(-\/-) mice (29 vs. 40 days in sgk1(+\/+) mice). In conclusion, gene-targeted mice lacking SGK1 showed blunted volume retention, yet were not protected against renal fibrosis during experimental nephrotic syndrome."],"offsets":[[88,1777]]}],"entities":[{"id":"13468","type":"Chemical","text":["doxorubicin"],"offsets":[[48,59]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"13469","type":"Disease","text":["nephrotic syndrome"],"offsets":[[68,86]],"normalized":[{"db_name":"MESH","db_id":"D009404"}]},{"id":"13470","type":"Chemical","text":["Doxorubicin"],"offsets":[[88,99]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"13471","type":"Disease","text":["nephropathy"],"offsets":[[108,119]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"13472","type":"Chemical","text":["sodium"],"offsets":[[140,146]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"13473","type":"Disease","text":["volume retention"],"offsets":[[172,188]],"normalized":[{"db_name":"MESH","db_id":"D016055"}]},{"id":"13474","type":"Disease","text":["fibrosis"],"offsets":[[199,207]],"normalized":[{"db_name":"MESH","db_id":"D005355"}]},{"id":"13475","type":"Chemical","text":["aldosterone"],"offsets":[[213,224]],"normalized":[{"db_name":"MESH","db_id":"D000450"}]},{"id":"13476","type":"Disease","text":["fibrosis"],"offsets":[[361,369]],"normalized":[{"db_name":"MESH","db_id":"D005355"}]},{"id":"13477","type":"Disease","text":["volume retention"],"offsets":[[484,500]],"normalized":[{"db_name":"MESH","db_id":"D016055"}]},{"id":"13478","type":"Disease","text":["fibrosis"],"offsets":[[505,513]],"normalized":[{"db_name":"MESH","db_id":"D005355"}]},{"id":"13479","type":"Disease","text":["nephrotic syndrome"],"offsets":[[521,539]],"normalized":[{"db_name":"MESH","db_id":"D009404"}]},{"id":"13480","type":"Chemical","text":["doxorubicin"],"offsets":[[554,565]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"13481","type":"Chemical","text":["Doxorubicin"],"offsets":[[706,717]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"13482","type":"Disease","text":["proteinuria"],"offsets":[[746,757]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]},{"id":"13483","type":"Disease","text":["nephrotic 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{"id":"13537","document_id":"19299179","passages":[{"id":"13538","type":"title","text":["Severe and long lasting cholestasis after high-dose co-trimoxazole treatment for Pneumocystis pneumonia in HIV-infected patients--a report of two cases."],"offsets":[[0,152]]},{"id":"13539","type":"abstract","text":["Pneumocystis pneumonia (PCP), a common opportunistic infection in HIV-infected individuals, is generally treated with high doses of co-trimoxazole. However, treatment is often limited by adverse effects. Here, we report two cases of severely immunocompromised HIV-infected patients who developed severe intrahepatic cholestasis, and in one patient lesions mimicking liver abscess formation on radiologic exams, during co-trimoxazole treatment for PCP. Whereas patient 1 showed lesions of up to 1 cm readily detectable on magnetic resonance imaging under prolonged co-trimoxazole treatment, therapy of patient 2 was switched early."],"offsets":[[153,783]]}],"entities":[{"id":"13540","type":"Disease","text":["cholestasis"],"offsets":[[24,35]],"normalized":[{"db_name":"MESH","db_id":"D002779"}]},{"id":"13541","type":"Chemical","text":["co-trimoxazole"],"offsets":[[52,66]],"normalized":[{"db_name":"MESH","db_id":"D015662"}]},{"id":"13542","type":"Disease","text":["Pneumocystis pneumonia"],"offsets":[[81,103]],"normalized":[{"db_name":"MESH","db_id":"D011020"}]},{"id":"13543","type":"Disease","text":["HIV-infected"],"offsets":[[107,119]],"normalized":[{"db_name":"MESH","db_id":"D015658"}]},{"id":"13544","type":"Disease","text":["Pneumocystis pneumonia"],"offsets":[[153,175]],"normalized":[{"db_name":"MESH","db_id":"D011020"}]},{"id":"13545","type":"Disease","text":["PCP"],"offsets":[[177,180]],"normalized":[{"db_name":"MESH","db_id":"D011020"}]},{"id":"13546","type":"Disease","text":["opportunistic infection"],"offsets":[[192,215]],"normalized":[{"db_name":"MESH","db_id":"D009894"}]},{"id":"13547","type":"Disease","text":["HIV-infected"],"offsets":[[219,231]],"normalized":[{"db_name":"MESH","db_id":"D015658"}]},{"id":"13548","type":"Chemical","text":["co-trimoxazole"],"offsets":[[285,299]],"normalized":[{"db_name":"MESH","db_id":"D015662"}]},{"id":"13549","type":"Disease","text":["HIV-infected"],"offsets":[[413,425]],"normalized":[{"db_name":"MESH","db_id":"D015658"}]},{"id":"13550","type":"Disease","text":["intrahepatic cholestasis"],"offsets":[[456,480]],"normalized":[{"db_name":"MESH","db_id":"D002780"}]},{"id":"13551","type":"Disease","text":["liver abscess"],"offsets":[[519,532]],"normalized":[{"db_name":"MESH","db_id":"D008100"}]},{"id":"13552","type":"Chemical","text":["co-trimoxazole"],"offsets":[[571,585]],"normalized":[{"db_name":"MESH","db_id":"D015662"}]},{"id":"13553","type":"Disease","text":["PCP"],"offsets":[[600,603]],"normalized":[{"db_name":"MESH","db_id":"D011020"}]},{"id":"13554","type":"Chemical","text":["co-trimoxazole"],"offsets":[[717,731]],"normalized":[{"db_name":"MESH","db_id":"D015662"}]}],"events":[],"coreferences":[],"relations":[{"id":"13555","type":"CID","arg1_id":"13541","arg2_id":"13550","normalized":[]},{"id":"13556","type":"CID","arg1_id":"13548","arg2_id":"13550","normalized":[]},{"id":"13557","type":"CID","arg1_id":"13552","arg2_id":"13550","normalized":[]},{"id":"13558","type":"CID","arg1_id":"13554","arg2_id":"13550","normalized":[]}]}
{"id":"13559","document_id":"19356053","passages":[{"id":"13560","type":"title","text":["Clinically significant proteinuria following the administration of sirolimus to renal transplant recipients."],"offsets":[[0,108]]},{"id":"13561","type":"abstract","text":["BACKGROUND: Sirolimus is the latest immunosuppressive agent used to prevent rejection, and may have less nephrotoxicity than calcineurin inhibitor (CNI)-based regimens. To date there has been little documentation of clinically significant proteinuria linked with the use of sirolimus. We have encountered several patients who developed substantial proteinuria associated with sirolimus use. In each patient, the close temporal association between the commencement of sirolimus therapy and proteinuria implicated sirolimus as the most likely etiology of the proteinuria. METHODS: We analyzed the clinical and laboratory information available for all 119 patients transplanted at the Washington Hospital Center between 1999-2003 for whom sirolimus was a component of their immunosuppressant regimen. In these patients, the magnitude of proteinuria was assessed on morning urine samples by turbidometric measurement or random urine protein:creatinine ratios, an estimate of grams of proteinuria\/day. Laboratory results were compared between prior, during and following sirolimus use. RESULTS: Twenty-eight patients (24%) developed increased proteinuria from baseline during their post-transplantation course. In 21 patients an alternative cause of proteinuria was either obvious or insufficient data was available to be conclusive. In 7 of the 28 patients there was a striking temporal association between the initiation of sirolimus and the development of nephrotic-range proteinuria. Proteinuria correlated most strongly with sirolimus therapy when compared to other demographic and clinical variables. In most patients, discontinuation of sirolimus resulted in a decrease, but not resolution, of proteinuria. CONCLUSIONS: Sirolimus induces or aggravates pre-existing proteinuria in an unpredictable subset of renal allograft recipients. Proteinuria may improve, but does not resolve, when sirolimus is 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{"id":"13774","document_id":"19729346","passages":[{"id":"13775","type":"title","text":["Comparative cognitive and subjective side effects of immediate-release oxycodone in healthy middle-aged and older adults."],"offsets":[[0,121]]},{"id":"13776","type":"abstract","text":["This study measured the objective and subjective neurocognitive effects of a single 10-mg dose of immediate-release oxycodone in healthy, older (> 65 years), and middle-aged (35 to 55 years) adults who were not suffering from chronic or significant daily pain. Seventy-one participants completed 2 separate study days and were blind to medication condition (placebo, 10-mg oxycodone). Plasma oxycodone concentration peaked between 60 and 90 minutes postdose (P < .01) and pupil size, an indication of physiological effects of the medication, peaked at approximately 90 to 120 minutes postdose (P < .01). Significant declines in simple and sustained attention, working memory, and verbal memory were observed at 1 hour postdose compared to baseline for both age groups with a trend toward return to baseline by 5 hours postdose. For almost all cognitive measures, there were no medication by age-interaction effects, which indicates that the 2 age groups exhibited similar responses to the medication challenge. This study suggests that for healthy older adults who are not suffering from chronic pain, neurocognitive and pharmacodynamic changes in response to a 10-mg dose of immediate-release oxycodone are similar to those observed for middle-aged adults. PERSPECTIVE: Study findings indicate that the metabolism, neurocognitive effects, and physical side effects of oral oxycodone are similar for healthy middle-aged and older adults. Therefore, clinicians should not avoid prescribing oral opioids to older adults based on the belief that older adults are at higher risk for side effects than younger adults."],"offsets":[[122,1734]]}],"entities":[{"id":"13777","type":"Chemical","text":["oxycodone"],"offsets":[[71,80]],"normalized":[{"db_name":"MESH","db_id":"D010098"}]},{"id":"13778","type":"Chemical","text":["oxycodone"],"offsets":[[238,247]],"normalized":[{"db_name":"MESH","db_id":"D010098"}]},{"id":"13779","type":"Disease","text":["pain"],"offsets":[[377,381]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"13780","type":"Chemical","text":["oxycodone"],"offsets":[[495,504]],"normalized":[{"db_name":"MESH","db_id":"D010098"}]},{"id":"13781","type":"Chemical","text":["oxycodone"],"offsets":[[514,523]],"normalized":[{"db_name":"MESH","db_id":"D010098"}]},{"id":"13782","type":"Disease","text":["declines in simple and sustained attention, working memory, and verbal memory"],"offsets":[[738,815]],"normalized":[{"db_name":"MESH","db_id":"D003072"},{"db_name":"MESH","db_id":"D008569"}]},{"id":"13783","type":"Disease","text":["declines in simple and sustained attention"],"offsets":[[738,780]],"normalized":[{"db_name":"MESH","db_id":"D003072"}]},{"id":"13784","type":"Disease","text":["declines in","working memory, and verbal memory"],"offsets":[[738,749],[782,815]],"normalized":[{"db_name":"MESH","db_id":"D008569"}]},{"id":"13785","type":"Disease","text":["chronic pain"],"offsets":[[1210,1222]],"normalized":[{"db_name":"MESH","db_id":"D059350"}]},{"id":"13786","type":"Chemical","text":["oxycodone"],"offsets":[[1316,1325]],"normalized":[{"db_name":"MESH","db_id":"D010098"}]},{"id":"13787","type":"Chemical","text":["oxycodone"],"offsets":[[1496,1505]],"normalized":[{"db_name":"MESH","db_id":"D010098"}]}],"events":[],"coreferences":[],"relations":[{"id":"13788","type":"CID","arg1_id":"13777","arg2_id":"13782","normalized":[]},{"id":"13789","type":"CID","arg1_id":"13777","arg2_id":"13784","normalized":[]},{"id":"13790","type":"CID","arg1_id":"13778","arg2_id":"13782","normalized":[]},{"id":"13791","type":"CID","arg1_id":"13778","arg2_id":"13784","normalized":[]},{"id":"13792","type":"CID","arg1_id":"13780","arg2_id":"13782","normalized":[]},{"id":"13793","type":"CID","arg1_id":"13780","arg2_id":"13784","normalized":[]},{"id":"13794","type":"CID","arg1_id":"13781","arg2_id":"13782","normalized":[]},{"id":"13795","type":"CID","arg1_id":"13781","arg2_id":"13784","normalized":[]},{"id":"13796","type":"CID","arg1_id":"13786","arg2_id":"13782","normalized":[]},{"id":"13797","type":"CID","arg1_id":"13786","arg2_id":"13784","normalized":[]},{"id":"13798","type":"CID","arg1_id":"13787","arg2_id":"13782","normalized":[]},{"id":"13799","type":"CID","arg1_id":"13787","arg2_id":"13784","normalized":[]},{"id":"13800","type":"CID","arg1_id":"13777","arg2_id":"13782","normalized":[]},{"id":"13801","type":"CID","arg1_id":"13777","arg2_id":"13783","normalized":[]},{"id":"13802","type":"CID","arg1_id":"13778","arg2_id":"13782","normalized":[]},{"id":"13803","type":"CID","arg1_id":"13778","arg2_id":"13783","normalized":[]},{"id":"13804","type":"CID","arg1_id":"13780","arg2_id":"13782","normalized":[]},{"id":"13805","type":"CID","arg1_id":"13780","arg2_id":"13783","normalized":[]},{"id":"13806","type":"CID","arg1_id":"13781","arg2_id":"13782","normalized":[]},{"id":"13807","type":"CID","arg1_id":"13781","arg2_id":"13783","normalized":[]},{"id":"13808","type":"CID","arg1_id":"13786","arg2_id":"13782","normalized":[]},{"id":"13809","type":"CID","arg1_id":"13786","arg2_id":"13783","normalized":[]},{"id":"13810","type":"CID","arg1_id":"13787","arg2_id":"13782","normalized":[]},{"id":"13811","type":"CID","arg1_id":"13787","arg2_id":"13783","normalized":[]}]}
{"id":"13812","document_id":"20080983","passages":[{"id":"13813","type":"title","text":["Normalizing effects of modafinil on sleep in chronic cocaine users."],"offsets":[[0,67]]},{"id":"13814","type":"abstract","text":["OBJECTIVE: The purpose of the present study was to determine the effect of morning-dosed modafinil on sleep and daytime sleepiness in chronic cocaine users. METHOD: Twenty cocaine-dependent participants were randomly assigned to receive modafinil, 400 mg (N=10), or placebo (N=10) every morning at 7:30 a.m. for 16 days in an inpatient, double-blind randomized trial. Participants underwent polysomnographic sleep recordings on days 1 to 3, 7 to 9, and 14 to 16 (first, second, and third weeks of abstinence). The Multiple Sleep Latency Test was performed at 11:30 a.m., 2:00 p.m., and 4:30 p.m. on days 2, 8, and 15. For comparison of sleep architecture variables, 12 healthy comparison participants underwent a single night of experimental polysomnography that followed 1 night of accommodation polysomnography. RESULTS: Progressive abstinence from cocaine was associated with worsening of all measured polysomnographic sleep outcomes. Compared with placebo, modafinil decreased nighttime sleep latency and increased slow-wave sleep time in cocaine-dependent participants. The effect of modafinil interacted with the abstinence week and was associated with longer total sleep time and shorter REM sleep latency in the third week of abstinence. Comparison of slow-wave sleep time, total sleep time, and sleep latency in cocaine-dependent and healthy participants revealed a normalizing effect of modafinil in cocaine-dependent participants. Modafinil was associated with increased daytime sleep latency, as measured by the Multiple Sleep Latency Test, and a nearly significant decrease in subjective daytime sleepiness. CONCLUSIONS: Morning-dosed modafinil promotes nocturnal sleep, normalizes sleep architecture, and decreases daytime sleepiness in abstinent cocaine users. These effects may be relevant in the treatment of cocaine dependence."],"offsets":[[68,1913]]}],"entities":[{"id":"13815","type":"Chemical","text":["modafinil"],"offsets":[[23,32]],"normalized":[{"db_name":"MESH","db_id":"C048833"}]},{"id":"13816","type":"Chemical","text":["cocaine"],"offsets":[[53,60]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"13817","type":"Chemical","text":["modafinil"],"offsets":[[157,166]],"normalized":[{"db_name":"MESH","db_id":"C048833"}]},{"id":"13818","type":"Disease","text":["daytime sleepiness"],"offsets":[[180,198]],"normalized":[{"db_name":"MESH","db_id":"D012893"}]},{"id":"13819","type":"Chemical","text":["cocaine"],"offsets":[[210,217]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"13820","type":"Chemical","text":["cocaine"],"offsets":[[240,247]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"13821","type":"Chemical","text":["modafinil"],"offsets":[[305,314]],"normalized":[{"db_name":"MESH","db_id":"C048833"}]},{"id":"13822","type":"Chemical","text":["cocaine"],"offsets":[[919,926]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"13823","type":"Chemical","text":["modafinil"],"offsets":[[1029,1038]],"normalized":[{"db_name":"MESH","db_id":"C048833"}]},{"id":"13824","type":"Chemical","text":["cocaine"],"offsets":[[1111,1118]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"13825","type":"Chemical","text":["modafinil"],"offsets":[[1157,1166]],"normalized":[{"db_name":"MESH","db_id":"C048833"}]},{"id":"13826","type":"Chemical","text":["cocaine"],"offsets":[[1389,1396]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"13827","type":"Chemical","text":["modafinil"],"offsets":[[1465,1474]],"normalized":[{"db_name":"MESH","db_id":"C048833"}]},{"id":"13828","type":"Chemical","text":["cocaine"],"offsets":[[1478,1485]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"13829","type":"Chemical","text":["Modafinil"],"offsets":[[1510,1519]],"normalized":[{"db_name":"MESH","db_id":"C048833"}]},{"id":"13830","type":"Disease","text":["daytime sleepiness"],"offsets":[[1669,1687]],"normalized":[{"db_name":"MESH","db_id":"D012893"}]},{"id":"13831","type":"Chemical","text":["modafinil"],"offsets":[[1716,1725]],"normalized":[{"db_name":"MESH","db_id":"C048833"}]},{"id":"13832","type":"Disease","text":["daytime sleepiness"],"offsets":[[1797,1815]],"normalized":[{"db_name":"MESH","db_id":"D012893"}]},{"id":"13833","type":"Chemical","text":["cocaine"],"offsets":[[1829,1836]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"13834","type":"Chemical","text":["cocaine"],"offsets":[[1894,1901]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]}],"events":[],"coreferences":[],"relations":[{"id":"13835","type":"CID","arg1_id":"13816","arg2_id":"13818","normalized":[]},{"id":"13836","type":"CID","arg1_id":"13816","arg2_id":"13830","normalized":[]},{"id":"13837","type":"CID","arg1_id":"13816","arg2_id":"13832","normalized":[]},{"id":"13838","type":"CID","arg1_id":"13819","arg2_id":"13818","normalized":[]},{"id":"13839","type":"CID","arg1_id":"13819","arg2_id":"13830","normalized":[]},{"id":"13840","type":"CID","arg1_id":"13819","arg2_id":"13832","normalized":[]},{"id":"13841","type":"CID","arg1_id":"13820","arg2_id":"13818","normalized":[]},{"id":"13842","type":"CID","arg1_id":"13820","arg2_id":"13830","normalized":[]},{"id":"13843","type":"CID","arg1_id":"13820","arg2_id":"13832","normalized":[]},{"id":"13844","type":"CID","arg1_id":"13822","arg2_id":"13818","normalized":[]},{"id":"13845","type":"CID","arg1_id":"13822","arg2_id":"13830","normalized":[]},{"id":"13846","type":"CID","arg1_id":"13822","arg2_id":"13832","normalized":[]},{"id":"13847","type":"CID","arg1_id":"13824","arg2_id":"13818","normalized":[]},{"id":"13848","type":"CID","arg1_id":"13824","arg2_id":"13830","normalized":[]},{"id":"13849","type":"CID","arg1_id":"13824","arg2_id":"13832","normalized":[]},{"id":"13850","type":"CID","arg1_id":"13826","arg2_id":"13818","normalized":[]},{"id":"13851","type":"CID","arg1_id":"13826","arg2_id":"13830","normalized":[]},{"id":"13852","type":"CID","arg1_id":"13826","arg2_id":"13832","normalized":[]},{"id":"13853","type":"CID","arg1_id":"13828","arg2_id":"13818","normalized":[]},{"id":"13854","type":"CID","arg1_id":"13828","arg2_id":"13830","normalized":[]},{"id":"13855","type":"CID","arg1_id":"13828","arg2_id":"13832","normalized":[]},{"id":"13856","type":"CID","arg1_id":"13833","arg2_id":"13818","normalized":[]},{"id":"13857","type":"CID","arg1_id":"13833","arg2_id":"13830","normalized":[]},{"id":"13858","type":"CID","arg1_id":"13833","arg2_id":"13832","normalized":[]},{"id":"13859","type":"CID","arg1_id":"13834","arg2_id":"13818","normalized":[]},{"id":"13860","type":"CID","arg1_id":"13834","arg2_id":"13830","normalized":[]},{"id":"13861","type":"CID","arg1_id":"13834","arg2_id":"13832","normalized":[]}]}
{"id":"13862","document_id":"20520283","passages":[{"id":"13863","type":"title","text":["Efficacy and safety of asenapine in a placebo- and haloperidol-controlled trial in patients with acute exacerbation of schizophrenia."],"offsets":[[0,133]]},{"id":"13864","type":"abstract","text":["Asenapine is approved by the Food and Drugs Administration in adults for acute treatment of schizophrenia or of manic or mixed episodes associated with bipolar I disorder with or without psychotic features. In a double-blind 6-week trial, 458 patients with acute schizophrenia were randomly assigned to fixed-dose treatment with asenapine at 5 mg twice daily (BID), asenapine at 10 mg BID, placebo, or haloperidol at 4 mg BID (to verify assay sensitivity). With last observations carried forward (LOCF), mean Positive and Negative Syndrome Scale total score reductions from baseline to endpoint were significantly greater with asenapine at 5 mg BID (-16.2) and haloperidol (-15.4) than placebo (-10.7; both P < 0.05); using mixed model for repeated measures (MMRM), changes at day 42 were significantly greater with asenapine at 5 and 10 mg BID (-21.3 and -19.4, respectively) and haloperidol (-20.0) than placebo (-14.6; all P < 0.05). On the Positive and Negative Syndrome Scale positive subscale, all treatments were superior to placebo with LOCF and MMRM; asenapine at 5 mg BID was superior to placebo on the negative subscale with MMRM and on the general psychopathology subscale with LOCF and MMRM. Treatment-related adverse events (AEs) occurred in 44% and 52%, 57%, and 41% of the asenapine at 5 and 10 mg BID, haloperidol, and placebo groups, respectively. Extrapyramidal symptoms reported as AEs occurred in 15% and 18%, 34%, and 10% of the asenapine at 5 and 10 mg BID, haloperidol, and placebo groups, respectively. Across all groups, no more than 5% of patients had clinically significant weight change. Post hoc analyses indicated that efficacy was similar with asenapine and haloperidol; greater contrasts were seen in AEs, especially extrapyramidal symptoms."],"offsets":[[134,1908]]}],"entities":[{"id":"13865","type":"Chemical","text":["asenapine"],"offsets":[[23,32]],"normalized":[{"db_name":"MESH","db_id":"C522667"}]},{"id":"13866","type":"Chemical","text":["haloperidol"],"offsets":[[51,62]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"13867","type":"Disease","text":["schizophrenia"],"offsets":[[119,132]],"normalized":[{"db_name":"MESH","db_id":"D012559"}]},{"id":"13868","type":"Chemical","text":["Asenapine"],"offsets":[[134,143]],"normalized":[{"db_name":"MESH","db_id":"C522667"}]},{"id":"13869","type":"Disease","text":["schizophrenia"],"offsets":[[226,239]],"normalized":[{"db_name":"MESH","db_id":"D012559"}]},{"id":"13870","type":"Disease","text":["manic"],"offsets":[[246,251]],"normalized":[{"db_name":"MESH","db_id":"D001714"}]},{"id":"13871","type":"Disease","text":["bipolar I disorder"],"offsets":[[286,304]],"normalized":[{"db_name":"MESH","db_id":"D001714"}]},{"id":"13872","type":"Disease","text":["psychotic"],"offsets":[[321,330]],"normalized":[{"db_name":"MESH","db_id":"D011618"}]},{"id":"13873","type":"Disease","text":["schizophrenia"],"offsets":[[397,410]],"normalized":[{"db_name":"MESH","db_id":"D012559"}]},{"id":"13874","type":"Chemical","text":["asenapine"],"offsets":[[463,472]],"normalized":[{"db_name":"MESH","db_id":"C522667"}]},{"id":"13875","type":"Chemical","text":["asenapine"],"offsets":[[500,509]],"normalized":[{"db_name":"MESH","db_id":"C522667"}]},{"id":"13876","type":"Chemical","text":["haloperidol"],"offsets":[[536,547]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"13877","type":"Chemical","text":["asenapine"],"offsets":[[761,770]],"normalized":[{"db_name":"MESH","db_id":"C522667"}]},{"id":"13878","type":"Chemical","text":["haloperidol"],"offsets":[[795,806]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"13879","type":"Chemical","text":["asenapine"],"offsets":[[950,959]],"normalized":[{"db_name":"MESH","db_id":"C522667"}]},{"id":"13880","type":"Chemical","text":["haloperidol"],"offsets":[[1015,1026]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"13881","type":"Chemical","text":["asenapine"],"offsets":[[1194,1203]],"normalized":[{"db_name":"MESH","db_id":"C522667"}]},{"id":"13882","type":"Chemical","text":["asenapine"],"offsets":[[1423,1432]],"normalized":[{"db_name":"MESH","db_id":"C522667"}]},{"id":"13883","type":"Chemical","text":["haloperidol"],"offsets":[[1453,1464]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"13884","type":"Disease","text":["Extrapyramidal symptoms"],"offsets":[[1500,1523]],"normalized":[{"db_name":"MESH","db_id":"D001480"}]},{"id":"13885","type":"Chemical","text":["asenapine"],"offsets":[[1585,1594]],"normalized":[{"db_name":"MESH","db_id":"C522667"}]},{"id":"13886","type":"Chemical","text":["haloperidol"],"offsets":[[1615,1626]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"13887","type":"Chemical","text":["asenapine"],"offsets":[[1810,1819]],"normalized":[{"db_name":"MESH","db_id":"C522667"}]},{"id":"13888","type":"Chemical","text":["haloperidol"],"offsets":[[1824,1835]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"13889","type":"Disease","text":["extrapyramidal symptoms"],"offsets":[[1884,1907]],"normalized":[{"db_name":"MESH","db_id":"D001480"}]}],"events":[],"coreferences":[],"relations":[{"id":"13890","type":"CID","arg1_id":"13866","arg2_id":"13884","normalized":[]},{"id":"13891","type":"CID","arg1_id":"13866","arg2_id":"13889","normalized":[]},{"id":"13892","type":"CID","arg1_id":"13876","arg2_id":"13884","normalized":[]},{"id":"13893","type":"CID","arg1_id":"13876","arg2_id":"13889","normalized":[]},{"id":"13894","type":"CID","arg1_id":"13878","arg2_id":"13884","normalized":[]},{"id":"13895","type":"CID","arg1_id":"13878","arg2_id":"13889","normalized":[]},{"id":"13896","type":"CID","arg1_id":"13880","arg2_id":"13884","normalized":[]},{"id":"13897","type":"CID","arg1_id":"13880","arg2_id":"13889","normalized":[]},{"id":"13898","type":"CID","arg1_id":"13883","arg2_id":"13884","normalized":[]},{"id":"13899","type":"CID","arg1_id":"13883","arg2_id":"13889","normalized":[]},{"id":"13900","type":"CID","arg1_id":"13886","arg2_id":"13884","normalized":[]},{"id":"13901","type":"CID","arg1_id":"13886","arg2_id":"13889","normalized":[]},{"id":"13902","type":"CID","arg1_id":"13888","arg2_id":"13884","normalized":[]},{"id":"13903","type":"CID","arg1_id":"13888","arg2_id":"13889","normalized":[]},{"id":"13904","type":"CID","arg1_id":"13865","arg2_id":"13884","normalized":[]},{"id":"13905","type":"CID","arg1_id":"13865","arg2_id":"13889","normalized":[]},{"id":"13906","type":"CID","arg1_id":"13868","arg2_id":"13884","normalized":[]},{"id":"13907","type":"CID","arg1_id":"13868","arg2_id":"13889","normalized":[]},{"id":"13908","type":"CID","arg1_id":"13874","arg2_id":"13884","normalized":[]},{"id":"13909","type":"CID","arg1_id":"13874","arg2_id":"13889","normalized":[]},{"id":"13910","type":"CID","arg1_id":"13875","arg2_id":"13884","normalized":[]},{"id":"13911","type":"CID","arg1_id":"13875","arg2_id":"13889","normalized":[]},{"id":"13912","type":"CID","arg1_id":"13877","arg2_id":"13884","normalized":[]},{"id":"13913","type":"CID","arg1_id":"13877","arg2_id":"13889","normalized":[]},{"id":"13914","type":"CID","arg1_id":"13879","arg2_id":"13884","normalized":[]},{"id":"13915","type":"CID","arg1_id":"13879","arg2_id":"13889","normalized":[]},{"id":"13916","type":"CID","arg1_id":"13881","arg2_id":"13884","normalized":[]},{"id":"13917","type":"CID","arg1_id":"13881","arg2_id":"13889","normalized":[]},{"id":"13918","type":"CID","arg1_id":"13882","arg2_id":"13884","normalized":[]},{"id":"13919","type":"CID","arg1_id":"13882","arg2_id":"13889","normalized":[]},{"id":"13920","type":"CID","arg1_id":"13885","arg2_id":"13884","normalized":[]},{"id":"13921","type":"CID","arg1_id":"13885","arg2_id":"13889","normalized":[]},{"id":"13922","type":"CID","arg1_id":"13887","arg2_id":"13884","normalized":[]},{"id":"13923","type":"CID","arg1_id":"13887","arg2_id":"13889","normalized":[]}]}
{"id":"13924","document_id":"20588063","passages":[{"id":"13925","type":"title","text":["Permeability, ultrastructural changes, and distribution of novel proteins in the glomerular barrier in early puromycin aminonucleoside nephrosis."],"offsets":[[0,145]]},{"id":"13926","type":"abstract","text":["BACKGROUND\/AIMS: It is still unclear what happens in the glomerulus when proteinuria starts. Using puromycin aminonucleoside nephrosis (PAN) rats, we studied early ultrastructural and permeability changes in relation to the expression of the podocyte-associated molecules nephrin, a-actinin, dendrin, and plekhh2, the last two of which were only recently discovered in podocytes. METHODS: Using immune stainings, semiquantitative measurement was performed under the electron microscope. Permeability was assessed using isolated kidney perfusion with tracers. Possible effects of ACE inhibition were tested. RESULTS: By day 2, some patchy foot process effacement, but no proteinuria, appeared. The amount of nephrin was reduced in both diseased and normal areas. The other proteins showed few changes, which were limited to diseased areas. By day 4, foot process effacement was complete and proteinuria appeared in parallel with signs of size barrier damage. Nephrin decreased further, while dendrin and plekhh2 also decreased but a-actinin remained unchanged. ACE inhibition had no significant protective effect. CONCLUSIONS: PAN glomeruli already showed significant pathology by day 4, despite relatively mild proteinuria. This was preceded by altered nephrin expression, supporting its pivotal role in podocyte morphology. The novel proteins dendrin and plekhh2 were both reduced, suggesting roles in PAN, whereas a-actinin was unchanged."],"offsets":[[146,1586]]}],"entities":[{"id":"13927","type":"Chemical","text":["puromycin aminonucleoside"],"offsets":[[109,134]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"13928","type":"Disease","text":["nephrosis"],"offsets":[[135,144]],"normalized":[{"db_name":"MESH","db_id":"D009401"}]},{"id":"13929","type":"Disease","text":["proteinuria"],"offsets":[[219,230]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]},{"id":"13930","type":"Chemical","text":["puromycin aminonucleoside"],"offsets":[[245,270]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"13931","type":"Disease","text":["nephrosis"],"offsets":[[271,280]],"normalized":[{"db_name":"MESH","db_id":"D009401"}]},{"id":"13932","type":"Disease","text":["proteinuria"],"offsets":[[816,827]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]},{"id":"13933","type":"Disease","text":["proteinuria"],"offsets":[[1036,1047]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]},{"id":"13934","type":"Disease","text":["proteinuria"],"offsets":[[1357,1368]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]}],"events":[],"coreferences":[],"relations":[{"id":"13935","type":"CID","arg1_id":"13927","arg2_id":"13929","normalized":[]},{"id":"13936","type":"CID","arg1_id":"13927","arg2_id":"13932","normalized":[]},{"id":"13937","type":"CID","arg1_id":"13927","arg2_id":"13933","normalized":[]},{"id":"13938","type":"CID","arg1_id":"13927","arg2_id":"13934","normalized":[]},{"id":"13939","type":"CID","arg1_id":"13930","arg2_id":"13929","normalized":[]},{"id":"13940","type":"CID","arg1_id":"13930","arg2_id":"13932","normalized":[]},{"id":"13941","type":"CID","arg1_id":"13930","arg2_id":"13933","normalized":[]},{"id":"13942","type":"CID","arg1_id":"13930","arg2_id":"13934","normalized":[]},{"id":"13943","type":"CID","arg1_id":"13927","arg2_id":"13928","normalized":[]},{"id":"13944","type":"CID","arg1_id":"13927","arg2_id":"13931","normalized":[]},{"id":"13945","type":"CID","arg1_id":"13930","arg2_id":"13928","normalized":[]},{"id":"13946","type":"CID","arg1_id":"13930","arg2_id":"13931","normalized":[]}]}
{"id":"13947","document_id":"19820426","passages":[{"id":"13948","type":"title","text":["Twin preterm neonates with cardiac toxicity related to lopinavir\/ritonavir therapy."],"offsets":[[0,83]]},{"id":"13949","type":"abstract","text":["We report twin neonates who were born prematurely at 32 weeks of gestation to a mother with human immunodeficiency virus infection. One of the twins developed complete heart block and dilated cardiomyopathy related to lopinavir\/ritonavir therapy, a boosted protease-inhibitor agent, while the other twin developed mild bradycardia. We recommend caution in the use of lopinavir\/ritonavir in the immediate neonatal period."],"offsets":[[84,504]]}],"entities":[{"id":"13950","type":"Disease","text":["cardiac toxicity"],"offsets":[[27,43]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"13951","type":"Chemical","text":["lopinavir\/ritonavir"],"offsets":[[55,74]],"normalized":[{"db_name":"MESH","db_id":"C558899"}]},{"id":"13952","type":"Disease","text":["human immunodeficiency virus infection"],"offsets":[[176,214]],"normalized":[{"db_name":"MESH","db_id":"D015658"}]},{"id":"13953","type":"Disease","text":["heart block"],"offsets":[[252,263]],"normalized":[{"db_name":"MESH","db_id":"D006327"}]},{"id":"13954","type":"Disease","text":["dilated cardiomyopathy"],"offsets":[[268,290]],"normalized":[{"db_name":"MESH","db_id":"D002311"}]},{"id":"13955","type":"Chemical","text":["lopinavir\/ritonavir"],"offsets":[[302,321]],"normalized":[{"db_name":"MESH","db_id":"C558899"}]},{"id":"13956","type":"Disease","text":["bradycardia"],"offsets":[[403,414]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"13957","type":"Chemical","text":["lopinavir\/ritonavir"],"offsets":[[451,470]],"normalized":[{"db_name":"MESH","db_id":"C558899"}]}],"events":[],"coreferences":[],"relations":[{"id":"13958","type":"CID","arg1_id":"13951","arg2_id":"13954","normalized":[]},{"id":"13959","type":"CID","arg1_id":"13955","arg2_id":"13954","normalized":[]},{"id":"13960","type":"CID","arg1_id":"13957","arg2_id":"13954","normalized":[]},{"id":"13961","type":"CID","arg1_id":"13951","arg2_id":"13953","normalized":[]},{"id":"13962","type":"CID","arg1_id":"13955","arg2_id":"13953","normalized":[]},{"id":"13963","type":"CID","arg1_id":"13957","arg2_id":"13953","normalized":[]},{"id":"13964","type":"CID","arg1_id":"13951","arg2_id":"13956","normalized":[]},{"id":"13965","type":"CID","arg1_id":"13955","arg2_id":"13956","normalized":[]},{"id":"13966","type":"CID","arg1_id":"13957","arg2_id":"13956","normalized":[]}]}
{"id":"13967","document_id":"1616457","passages":[{"id":"13968","type":"title","text":["Learning of rats under amnesia caused by pentobarbital."],"offsets":[[0,55]]},{"id":"13969","type":"abstract","text":["Dissociated learning of rats in the normal state and the state of amnesia produced by pentobarbital (15 mg\/kg, ip) was carried out. Rats were trained to approach a shelf where they received food reinforcement. In Group 1 the rats were trained under the influence of pentobarbital to run to the same shelf as in the normal state. In Group 2 the rats were trained to approach different shelves in different drug states. It was shown that memory dissociation occurred in both groups. Differences in the parameters of training under the influence of pentobarbital between Groups 1 and 2 were revealed. These findings show that the brain-dissociated state induced by pentobarbital is formed with the participation of the mechanisms of information perception."],"offsets":[[56,809]]}],"entities":[{"id":"13970","type":"Disease","text":["amnesia"],"offsets":[[23,30]],"normalized":[{"db_name":"MESH","db_id":"D000647"}]},{"id":"13971","type":"Chemical","text":["pentobarbital"],"offsets":[[41,54]],"normalized":[{"db_name":"MESH","db_id":"D010424"}]},{"id":"13972","type":"Disease","text":["amnesia"],"offsets":[[122,129]],"normalized":[{"db_name":"MESH","db_id":"D000647"}]},{"id":"13973","type":"Chemical","text":["pentobarbital"],"offsets":[[142,155]],"normalized":[{"db_name":"MESH","db_id":"D010424"}]},{"id":"13974","type":"Chemical","text":["pentobarbital"],"offsets":[[322,335]],"normalized":[{"db_name":"MESH","db_id":"D010424"}]},{"id":"13975","type":"Disease","text":["memory dissociation"],"offsets":[[492,511]],"normalized":[{"db_name":"MESH","db_id":"D008569"}]},{"id":"13976","type":"Chemical","text":["pentobarbital"],"offsets":[[602,615]],"normalized":[{"db_name":"MESH","db_id":"D010424"}]},{"id":"13977","type":"Chemical","text":["pentobarbital"],"offsets":[[718,731]],"normalized":[{"db_name":"MESH","db_id":"D010424"}]}],"events":[],"coreferences":[],"relations":[{"id":"13978","type":"CID","arg1_id":"13971","arg2_id":"13970","normalized":[]},{"id":"13979","type":"CID","arg1_id":"13971","arg2_id":"13972","normalized":[]},{"id":"13980","type":"CID","arg1_id":"13973","arg2_id":"13970","normalized":[]},{"id":"13981","type":"CID","arg1_id":"13973","arg2_id":"13972","normalized":[]},{"id":"13982","type":"CID","arg1_id":"13974","arg2_id":"13970","normalized":[]},{"id":"13983","type":"CID","arg1_id":"13974","arg2_id":"13972","normalized":[]},{"id":"13984","type":"CID","arg1_id":"13976","arg2_id":"13970","normalized":[]},{"id":"13985","type":"CID","arg1_id":"13976","arg2_id":"13972","normalized":[]},{"id":"13986","type":"CID","arg1_id":"13977","arg2_id":"13970","normalized":[]},{"id":"13987","type":"CID","arg1_id":"13977","arg2_id":"13972","normalized":[]}]}
{"id":"13988","document_id":"567256","passages":[{"id":"13989","type":"title","text":["Angiosarcoma of the liver associated with diethylstilbestrol."],"offsets":[[0,61]]},{"id":"13990","type":"abstract","text":["Angiosarcoma of the liver occurred in a 76-year-old man who had been treated for a well-differentiated adenocarcinoma of the liver with diethylstilbestrol for 13 years. Angiosarcoma was also present within pulmonary and renal arteries. The possibility that the intraarterial lesions might represent independent primary tumors is considered."],"offsets":[[62,402]]}],"entities":[{"id":"13991","type":"Disease","text":["Angiosarcoma of the liver"],"offsets":[[0,25]],"normalized":[{"db_name":"MESH","db_id":"D006394"},{"db_name":"MESH","db_id":"D008113"}]},{"id":"13992","type":"Disease","text":["Angiosarcoma"],"offsets":[[0,12]],"normalized":[{"db_name":"MESH","db_id":"D006394"}]},{"id":"13993","type":"Disease","text":["Angiosarcoma of the liver"],"offsets":[[0,25]],"normalized":[{"db_name":"MESH","db_id":"D008113"}]},{"id":"13994","type":"Chemical","text":["diethylstilbestrol"],"offsets":[[42,60]],"normalized":[{"db_name":"MESH","db_id":"D004054"}]},{"id":"13995","type":"Disease","text":["Angiosarcoma of the liver"],"offsets":[[62,87]],"normalized":[{"db_name":"MESH","db_id":"D006394"},{"db_name":"MESH","db_id":"D008113"}]},{"id":"13996","type":"Disease","text":["Angiosarcoma"],"offsets":[[62,74]],"normalized":[{"db_name":"MESH","db_id":"D006394"}]},{"id":"13997","type":"Disease","text":["Angiosarcoma of the liver"],"offsets":[[62,87]],"normalized":[{"db_name":"MESH","db_id":"D008113"}]},{"id":"13998","type":"Disease","text":["adenocarcinoma of the liver"],"offsets":[[165,192]],"normalized":[{"db_name":"MESH","db_id":"D000230"},{"db_name":"MESH","db_id":"D008113"}]},{"id":"13999","type":"Disease","text":["adenocarcinoma"],"offsets":[[165,179]],"normalized":[{"db_name":"MESH","db_id":"D000230"}]},{"id":"14000","type":"Disease","text":["adenocarcinoma of the liver"],"offsets":[[165,192]],"normalized":[{"db_name":"MESH","db_id":"D008113"}]},{"id":"14001","type":"Chemical","text":["diethylstilbestrol"],"offsets":[[198,216]],"normalized":[{"db_name":"MESH","db_id":"D004054"}]},{"id":"14002","type":"Disease","text":["Angiosarcoma"],"offsets":[[231,243]],"normalized":[{"db_name":"MESH","db_id":"D006394"}]},{"id":"14003","type":"Disease","text":["intraarterial lesions"],"offsets":[[323,344]],"normalized":[{"db_name":"MESH","db_id":"D014652"}]},{"id":"14004","type":"Disease","text":["tumors"],"offsets":[[381,387]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]}],"events":[],"coreferences":[],"relations":[{"id":"14005","type":"CID","arg1_id":"13994","arg2_id":"13991","normalized":[]},{"id":"14006","type":"CID","arg1_id":"13994","arg2_id":"13993","normalized":[]},{"id":"14007","type":"CID","arg1_id":"13994","arg2_id":"13995","normalized":[]},{"id":"14008","type":"CID","arg1_id":"13994","arg2_id":"13997","normalized":[]},{"id":"14009","type":"CID","arg1_id":"13994","arg2_id":"13998","normalized":[]},{"id":"14010","type":"CID","arg1_id":"13994","arg2_id":"14000","normalized":[]},{"id":"14011","type":"CID","arg1_id":"14001","arg2_id":"13991","normalized":[]},{"id":"14012","type":"CID","arg1_id":"14001","arg2_id":"13993","normalized":[]},{"id":"14013","type":"CID","arg1_id":"14001","arg2_id":"13995","normalized":[]},{"id":"14014","type":"CID","arg1_id":"14001","arg2_id":"13997","normalized":[]},{"id":"14015","type":"CID","arg1_id":"14001","arg2_id":"13998","normalized":[]},{"id":"14016","type":"CID","arg1_id":"14001","arg2_id":"14000","normalized":[]},{"id":"14017","type":"CID","arg1_id":"13994","arg2_id":"13991","normalized":[]},{"id":"14018","type":"CID","arg1_id":"13994","arg2_id":"13992","normalized":[]},{"id":"14019","type":"CID","arg1_id":"13994","arg2_id":"13995","normalized":[]},{"id":"14020","type":"CID","arg1_id":"13994","arg2_id":"13996","normalized":[]},{"id":"14021","type":"CID","arg1_id":"13994","arg2_id":"14002","normalized":[]},{"id":"14022","type":"CID","arg1_id":"14001","arg2_id":"13991","normalized":[]},{"id":"14023","type":"CID","arg1_id":"14001","arg2_id":"13992","normalized":[]},{"id":"14024","type":"CID","arg1_id":"14001","arg2_id":"13995","normalized":[]},{"id":"14025","type":"CID","arg1_id":"14001","arg2_id":"13996","normalized":[]},{"id":"14026","type":"CID","arg1_id":"14001","arg2_id":"14002","normalized":[]}]}
{"id":"14027","document_id":"17439425","passages":[{"id":"14028","type":"title","text":["Role of xanthine oxidase in dexamethasone-induced hypertension in rats."],"offsets":[[0,71]]},{"id":"14029","type":"abstract","text":["1. Glucocorticoid-induced hypertension (GC-HT) in the rat is associated with nitric oxide-redox imbalance. 2. We studied the role of xanthine oxidase (XO), which is implicated in the production of reactive oxygen species, in dexamethasone-induced hypertension (dex-HT). 3. Thirty male Sprague-Dawley rats were divided randomly into four treatment groups: saline, dexamethasone (dex), allopurinol plus saline, and allopurinol plus dex. 4. Systolic blood pressures (SBP) and bodyweights were recorded each alternate day. Thymus weight was used as a marker of glucocorticoid activity, and serum urate to assess XO inhibition. 5. Dex increased SBP (110 +\/- 2-126 +\/- 3 mmHg; P < 0.001) and decreased thymus (P < 0.001) and bodyweights (P\" < 0.01). Allopurinol decreased serum urate from 76 +\/- 5 to 30 +\/- 3 micromol\/L (P < 0.001) in saline and from 84 +\/- 13 to 28 +\/- 2 micromol\/L in dex-treated (P < 0.01) groups. 6. Allopurinol did not prevent dex-HT. This, together with our previous findings that allopurinol failed to prevent adrenocorticotrophic hormone induced hypertension, suggests that XO activity is not a major determinant of GC-HT in the rat."],"offsets":[[72,1225]]}],"entities":[{"id":"14030","type":"Chemical","text":["xanthine"],"offsets":[[8,16]],"normalized":[{"db_name":"MESH","db_id":"D019820"}]},{"id":"14031","type":"Chemical","text":["dexamethasone"],"offsets":[[28,41]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"14032","type":"Disease","text":["hypertension"],"offsets":[[50,62]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"14033","type":"Disease","text":["hypertension"],"offsets":[[98,110]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"14034","type":"Disease","text":["HT"],"offsets":[[115,117]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"14035","type":"Chemical","text":["nitric oxide"],"offsets":[[149,161]],"normalized":[{"db_name":"MESH","db_id":"D009569"}]},{"id":"14036","type":"Chemical","text":["xanthine"],"offsets":[[205,213]],"normalized":[{"db_name":"MESH","db_id":"D019820"}]},{"id":"14037","type":"Chemical","text":["dexamethasone"],"offsets":[[297,310]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"14038","type":"Disease","text":["hypertension"],"offsets":[[319,331]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"14039","type":"Chemical","text":["dex"],"offsets":[[333,336]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"14040","type":"Disease","text":["HT"],"offsets":[[337,339]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"14041","type":"Chemical","text":["dexamethasone"],"offsets":[[435,448]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"14042","type":"Chemical","text":["dex"],"offsets":[[450,453]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"14043","type":"Chemical","text":["allopurinol"],"offsets":[[456,467]],"normalized":[{"db_name":"MESH","db_id":"D000493"}]},{"id":"14044","type":"Chemical","text":["allopurinol"],"offsets":[[485,496]],"normalized":[{"db_name":"MESH","db_id":"D000493"}]},{"id":"14045","type":"Chemical","text":["dex"],"offsets":[[502,505]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"14046","type":"Chemical","text":["urate"],"offsets":[[664,669]],"normalized":[{"db_name":"MESH","db_id":"D014527"}]},{"id":"14047","type":"Chemical","text":["Dex"],"offsets":[[698,701]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"14048","type":"Disease","text":["increased 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{"id":"14149","document_id":"9351491","passages":[{"id":"14150","type":"title","text":["Extrapyramidal side effects with risperidone and haloperidol at comparable D2 receptor occupancy levels."],"offsets":[[0,104]]},{"id":"14151","type":"abstract","text":["Risperidone is an antipsychotic drug with high affinity at dopamine D2 and serotonin 5-HT2 receptors. Previous clinical studies have proposed that risperidone's pharmacologic profile may produce improved efficacy for negative psychotic symptoms and decreased propensity for extrapyramidal side effects; features shared by so-called 'atypical' neuroleptics. To determine if routine risperidone treatment is associated with a unique degree of D2 receptor occupancy and pattern of clinical effects, we used [123I]IBZM SPECT to determine D2 occupancy in subjects treated with routine clinical doses of risperidone (n = 12) or haloperidol (n = 7). Both risperidone and haloperidol produced D2 occupancy levels between approximately 60 and 90% at standard clinical doses. There was no significant difference between occupancy levels obtained with haloperidol or risperidone. Drug-induced parkinsonism was observed in subjects treated with risperidone (42%) and haloperidol (29%) and was observed at occupancy levels above 60%. Based on these observations, it is concluded that 5-HT2 blockade obtained with risperidone at D2 occupancy rates of 60% and above does not appear to protect against the risk for extrapyramidal side effects."],"offsets":[[105,1332]]}],"entities":[{"id":"14152","type":"Chemical","text":["risperidone"],"offsets":[[33,44]],"normalized":[{"db_name":"MESH","db_id":"D018967"}]},{"id":"14153","type":"Chemical","text":["haloperidol"],"offsets":[[49,60]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"14154","type":"Chemical","text":["Risperidone"],"offsets":[[105,116]],"normalized":[{"db_name":"MESH","db_id":"D018967"}]},{"id":"14155","type":"Chemical","text":["dopamine"],"offsets":[[164,172]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"14156","type":"Chemical","text":["serotonin 5-HT2"],"offsets":[[180,195]],"normalized":[{"db_name":"MESH","db_id":"D044348"}]},{"id":"14157","type":"Chemical","text":["risperidone"],"offsets":[[252,263]],"normalized":[{"db_name":"MESH","db_id":"D018967"}]},{"id":"14158","type":"Disease","text":["psychotic symptoms"],"offsets":[[331,349]],"normalized":[{"db_name":"MESH","db_id":"D011618"}]},{"id":"14159","type":"Chemical","text":["risperidone"],"offsets":[[486,497]],"normalized":[{"db_name":"MESH","db_id":"D018967"}]},{"id":"14160","type":"Chemical","text":["risperidone"],"offsets":[[703,714]],"normalized":[{"db_name":"MESH","db_id":"D018967"}]},{"id":"14161","type":"Chemical","text":["haloperidol"],"offsets":[[727,738]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"14162","type":"Chemical","text":["risperidone"],"offsets":[[753,764]],"normalized":[{"db_name":"MESH","db_id":"D018967"}]},{"id":"14163","type":"Chemical","text":["haloperidol"],"offsets":[[769,780]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"14164","type":"Chemical","text":["haloperidol"],"offsets":[[946,957]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"14165","type":"Chemical","text":["risperidone"],"offsets":[[961,972]],"normalized":[{"db_name":"MESH","db_id":"D018967"}]},{"id":"14166","type":"Disease","text":["Drug-induced parkinsonism"],"offsets":[[974,999]],"normalized":[{"db_name":"MESH","db_id":"D010302"}]},{"id":"14167","type":"Chemical","text":["risperidone"],"offsets":[[1038,1049]],"normalized":[{"db_name":"MESH","db_id":"D018967"}]},{"id":"14168","type":"Chemical","text":["haloperidol"],"offsets":[[1060,1071]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"14169","type":"Chemical","text":["risperidone"],"offsets":[[1205,1216]],"normalized":[{"db_name":"MESH","db_id":"D018967"}]}],"events":[],"coreferences":[],"relations":[{"id":"14170","type":"CID","arg1_id":"14152","arg2_id":"14166","normalized":[]},{"id":"14171","type":"CID","arg1_id":"14154","arg2_id":"14166","normalized":[]},{"id":"14172","type":"CID","arg1_id":"14157","arg2_id":"14166","normalized":[]},{"id":"14173","type":"CID","arg1_id":"14159","arg2_id":"14166","normalized":[]},{"id":"14174","type":"CID","arg1_id":"14160","arg2_id":"14166","normalized":[]},{"id":"14175","type":"CID","arg1_id":"14162","arg2_id":"14166","normalized":[]},{"id":"14176","type":"CID","arg1_id":"14165","arg2_id":"14166","normalized":[]},{"id":"14177","type":"CID","arg1_id":"14167","arg2_id":"14166","normalized":[]},{"id":"14178","type":"CID","arg1_id":"14169","arg2_id":"14166","normalized":[]},{"id":"14179","type":"CID","arg1_id":"14153","arg2_id":"14166","normalized":[]},{"id":"14180","type":"CID","arg1_id":"14161","arg2_id":"14166","normalized":[]},{"id":"14181","type":"CID","arg1_id":"14163","arg2_id":"14166","normalized":[]},{"id":"14182","type":"CID","arg1_id":"14164","arg2_id":"14166","normalized":[]},{"id":"14183","type":"CID","arg1_id":"14168","arg2_id":"14166","normalized":[]}]}
{"id":"14184","document_id":"18752389","passages":[{"id":"14185","type":"title","text":["Simvastatin-ezetimibe-induced hepatic failure necessitating liver transplantation."],"offsets":[[0,82]]},{"id":"14186","type":"abstract","text":["Abstract Serum aminotransferase elevations are a commonly known adverse effect of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) therapy. However, hepatotoxic events have not been widely published with ezetimibe or the combination agent simvastatin-ezetimibe. We describe a 70-year-old Hispanic woman who developed fulminant hepatic failure necessitating liver transplantation 10 weeks after conversion from simvastatin 40 mg\/day to simvastatin 10 mg-ezetimibe 40 mg\/day. The patient's lipid panel had been maintained with simvastatin for 18 months before the conversion without evidence of hepatotoxicity. A routine laboratory work-up 10 weeks after conversion revealed elevated serum aminotransferase levels. Simvastatinezetimibe and escitalopram (which she was taking for depression) were discontinued, and other potential causes of hepatotoxicity were excluded. A repeat work-up revealed further elevations in aminotransferase levels, and liver biopsy revealed evidence of moderate-to-severe drug toxicity. She underwent liver transplantation with an uneventful postoperative course. Her aminotransferase levels returned to normal by postoperative day 23, and her 2-year follow-up showed no adverse events. Ezetimibe undergoes extensive glucuronidation by uridine diphosphate glucoronosyltransferases (UGT) in the intestine and liver and may have inhibited the glucuronidation of simvastatin hydroxy acid, resulting in increased simvastatin exposure and subsequent hepatotoxicity. To our knowledge, this is the first case report of simvastatin-ezetimibe-induced liver failure that resulted in liver transplantation. We postulate that the mechanism of the simvastatinezetimibe-induced hepatotoxicity is the increased simvastatin exposure by ezetimibe inhibition of UGT enzymes. Clinicians should be aware of potential hepatotoxicity with simvastatin-ezetimibe especially in elderly patients and should carefully monitor serum aminotransferase levels when starting therapy and titrating the dosage."],"offsets":[[83,2103]]}],"entities":[{"id":"14187","type":"Chemical","text":["Simvastatin-ezetimibe"],"offsets":[[0,21]],"normalized":[{"db_name":"MESH","db_id":"C492458"}]},{"id":"14188","type":"Disease","text":["hepatic failure"],"offsets":[[30,45]],"normalized":[{"db_name":"MESH","db_id":"D017093"}]},{"id":"14189","type":"Chemical","text":["statin"],"offsets":[[224,230]],"normalized":[{"db_name":"MESH","db_id":"D019821"}]},{"id":"14190","type":"Disease","text":["hepatotoxic"],"offsets":[[250,261]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"14191","type":"Chemical","text":["ezetimibe"],"offsets":[[305,314]],"normalized":[{"db_name":"MESH","db_id":"C108606"}]},{"id":"14192","type":"Chemical","text":["simvastatin-ezetimibe"],"offsets":[[340,361]],"normalized":[{"db_name":"MESH","db_id":"C492458"}]},{"id":"14193","type":"Disease","text":["fulminant hepatic failure"],"offsets":[[418,443]],"normalized":[{"db_name":"MESH","db_id":"D017114"}]},{"id":"14194","type":"Chemical","text":["simvastatin"],"offsets":[[511,522]],"normalized":[{"db_name":"MESH","db_id":"D019821"}]},{"id":"14195","type":"Chemical","text":["simvastatin 10 mg-ezetimibe 40 mg"],"offsets":[[536,569]],"normalized":[{"db_name":"MESH","db_id":"C492458"}]},{"id":"14196","type":"Chemical","text":["simvastatin"],"offsets":[[626,637]],"normalized":[{"db_name":"MESH","db_id":"D019821"}]},{"id":"14197","type":"Disease","text":["hepatotoxicity"],"offsets":[[694,708]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"14198","type":"Chemical","text":["Simvastatinezetimibe"],"offsets":[[814,834]],"normalized":[{"db_name":"MESH","db_id":"C492458"}]},{"id":"14199","type":"Chemical","text":["escitalopram"],"offsets":[[839,851]],"normalized":[{"db_name":"MESH","db_id":"D015283"}]},{"id":"14200","type":"Disease","text":["depression"],"offsets":[[878,888]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"14201","type":"Disease","text":["hepatotoxicity"],"offsets":[[939,953]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"14202","type":"Disease","text":["drug toxicity"],"offsets":[[1099,1112]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"14203","type":"Chemical","text":["Ezetimibe"],"offsets":[[1314,1323]],"normalized":[{"db_name":"MESH","db_id":"C108606"}]},{"id":"14204","type":"Chemical","text":["uridine diphosphate"],"offsets":[[1363,1382]],"normalized":[{"db_name":"MESH","db_id":"D014530"}]},{"id":"14205","type":"Chemical","text":["simvastatin hydroxy acid"],"offsets":[[1487,1511]],"normalized":[{"db_name":"MESH","db_id":"C532833"}]},{"id":"14206","type":"Chemical","text":["simvastatin"],"offsets":[[1536,1547]],"normalized":[{"db_name":"MESH","db_id":"D019821"}]},{"id":"14207","type":"Disease","text":["hepatotoxicity"],"offsets":[[1572,1586]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"14208","type":"Chemical","text":["simvastatin-ezetimibe"],"offsets":[[1639,1660]],"normalized":[{"db_name":"MESH","db_id":"C492458"}]},{"id":"14209","type":"Disease","text":["liver failure"],"offsets":[[1669,1682]],"normalized":[{"db_name":"MESH","db_id":"D017093"}]},{"id":"14210","type":"Chemical","text":["simvastatinezetimibe"],"offsets":[[1762,1782]],"normalized":[{"db_name":"MESH","db_id":"C492458"}]},{"id":"14211","type":"Disease","text":["hepatotoxicity"],"offsets":[[1791,1805]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"14212","type":"Chemical","text":["simvastatin"],"offsets":[[1823,1834]],"normalized":[{"db_name":"MESH","db_id":"D019821"}]},{"id":"14213","type":"Chemical","text":["ezetimibe"],"offsets":[[1847,1856]],"normalized":[{"db_name":"MESH","db_id":"C108606"}]},{"id":"14214","type":"Disease","text":["hepatotoxicity"],"offsets":[[1924,1938]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"14215","type":"Chemical","text":["simvastatin-ezetimibe"],"offsets":[[1944,1965]],"normalized":[{"db_name":"MESH","db_id":"C492458"}]}],"events":[],"coreferences":[],"relations":[{"id":"14216","type":"CID","arg1_id":"14187","arg2_id":"14190","normalized":[]},{"id":"14217","type":"CID","arg1_id":"14187","arg2_id":"14197","normalized":[]},{"id":"14218","type":"CID","arg1_id":"14187","arg2_id":"14201","normalized":[]},{"id":"14219","type":"CID","arg1_id":"14187","arg2_id":"14207","normalized":[]},{"id":"14220","type":"CID","arg1_id":"14187","arg2_id":"14211","normalized":[]},{"id":"14221","type":"CID","arg1_id":"14187","arg2_id":"14214","normalized":[]},{"id":"14222","type":"CID","arg1_id":"14192","arg2_id":"14190","normalized":[]},{"id":"14223","type":"CID","arg1_id":"14192","arg2_id":"14197","normalized":[]},{"id":"14224","type":"CID","arg1_id":"14192","arg2_id":"14201","normalized":[]},{"id":"14225","type":"CID","arg1_id":"14192","arg2_id":"14207","normalized":[]},{"id":"14226","type":"CID","arg1_id":"14192","arg2_id":"14211","normalized":[]},{"id":"14227","type":"CID","arg1_id":"14192","arg2_id":"14214","normalized":[]},{"id":"14228","type":"CID","arg1_id":"14195","arg2_id":"14190","normalized":[]},{"id":"14229","type":"CID","arg1_id":"14195","arg2_id":"14197","normalized":[]},{"id":"14230","type":"CID","arg1_id":"14195","arg2_id":"14201","normalized":[]},{"id":"14231","type":"CID","arg1_id":"14195","arg2_id":"14207","normalized":[]},{"id":"14232","type":"CID","arg1_id":"14195","arg2_id":"14211","normalized":[]},{"id":"14233","type":"CID","arg1_id":"14195","arg2_id":"14214","normalized":[]},{"id":"14234","type":"CID","arg1_id":"14198","arg2_id":"14190","normalized":[]},{"id":"14235","type":"CID","arg1_id":"14198","arg2_id":"14197","normalized":[]},{"id":"14236","type":"CID","arg1_id":"14198","arg2_id":"14201","normalized":[]},{"id":"14237","type":"CID","arg1_id":"14198","arg2_id":"14207","normalized":[]},{"id":"14238","type":"CID","arg1_id":"14198","arg2_id":"14211","normalized":[]},{"id":"14239","type":"CID","arg1_id":"14198","arg2_id":"14214","normalized":[]},{"id":"14240","type":"CID","arg1_id":"14208","arg2_id":"14190","normalized":[]},{"id":"14241","type":"CID","arg1_id":"14208","arg2_id":"14197","normalized":[]},{"id":"14242","type":"CID","arg1_id":"14208","arg2_id":"14201","normalized":[]},{"id":"14243","type":"CID","arg1_id":"14208","arg2_id":"14207","normalized":[]},{"id":"14244","type":"CID","arg1_id":"14208","arg2_id":"14211","normalized":[]},{"id":"14245","type":"CID","arg1_id":"14208","arg2_id":"14214","normalized":[]},{"id":"14246","type":"CID","arg1_id":"14210","arg2_id":"14190","normalized":[]},{"id":"14247","type":"CID","arg1_id":"14210","arg2_id":"14197","normalized":[]},{"id":"14248","type":"CID","arg1_id":"14210","arg2_id":"14201","normalized":[]},{"id":"14249","type":"CID","arg1_id":"14210","arg2_id":"14207","normalized":[]},{"id":"14250","type":"CID","arg1_id":"14210","arg2_id":"14211","normalized":[]},{"id":"14251","type":"CID","arg1_id":"14210","arg2_id":"14214","normalized":[]},{"id":"14252","type":"CID","arg1_id":"14215","arg2_id":"14190","normalized":[]},{"id":"14253","type":"CID","arg1_id":"14215","arg2_id":"14197","normalized":[]},{"id":"14254","type":"CID","arg1_id":"14215","arg2_id":"14201","normalized":[]},{"id":"14255","type":"CID","arg1_id":"14215","arg2_id":"14207","normalized":[]},{"id":"14256","type":"CID","arg1_id":"14215","arg2_id":"14211","normalized":[]},{"id":"14257","type":"CID","arg1_id":"14215","arg2_id":"14214","normalized":[]},{"id":"14258","type":"CID","arg1_id":"14187","arg2_id":"14193","normalized":[]},{"id":"14259","type":"CID","arg1_id":"14192","arg2_id":"14193","normalized":[]},{"id":"14260","type":"CID","arg1_id":"14195","arg2_id":"14193","normalized":[]},{"id":"14261","type":"CID","arg1_id":"14198","arg2_id":"14193","normalized":[]},{"id":"14262","type":"CID","arg1_id":"14208","arg2_id":"14193","normalized":[]},{"id":"14263","type":"CID","arg1_id":"14210","arg2_id":"14193","normalized":[]},{"id":"14264","type":"CID","arg1_id":"14215","arg2_id":"14193","normalized":[]}]}
{"id":"14265","document_id":"20098969","passages":[{"id":"14266","type":"title","text":["Oral manifestations of \"meth mouth\": a case report."],"offsets":[[0,51]]},{"id":"14267","type":"abstract","text":["AIM: The aim of the documentation of this clinical case is to make clinicians aware of \"meth mouth\" and the medical risks associated with this serious condition. BACKGROUND: Methamphetamine is a very addictive, powerful stimulant that increases wakefulness and physical activity and can produce other effects such as cardiac dysrhythmias, hypertension, hallucinations, and violent behavior. Dental patients abusing methamphetamine can present with poor oral hygiene, xerostomia, rampant caries (\"meth mouth\"), and excessive tooth wear. Oral rehabilitation of patients using methamphetamine can be challenging. CASE DESCRIPTION: A 30-year-old Caucasian woman presented with dental pain, bad breath, and self-reported poor esthetics. A comprehensive examination including her medical history, panoramic radiograph, and intraoral examination revealed 19 carious lesions, which is not very common for a healthy adult. She reported her use of methamphetamine for five years and had not experienced any major carious episodes before she started using the drug. SUMMARY: The patient's medical and dental histories along with radiographic and clinical findings lead to a diagnosis of \"meth mouth.\" Although three different dental treatment modalities (either conventional or implant-supported) have been offered to the patient since August 2007, the patient has yet to initiate any treatment. CLINICAL SIGNIFICANCE: This clinical case showing oral manifestations of meth mouth was presented to help dental practitioners recognize and manage patients who may be abusing methamphetamines. Dental practitioners also may be skeptical about the reliability of appointment keeping by these patients, as they frequently miss their appointments without reasonable justification."],"offsets":[[52,1814]]}],"entities":[{"id":"14268","type":"Disease","text":["meth mouth"],"offsets":[[24,34]],"normalized":[]},{"id":"14269","type":"Disease","text":["meth mouth"],"offsets":[[140,150]],"normalized":[]},{"id":"14270","type":"Chemical","text":["Methamphetamine"],"offsets":[[226,241]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"14271","type":"Disease","text":["cardiac dysrhythmias"],"offsets":[[369,389]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"14272","type":"Disease","text":["hypertension"],"offsets":[[391,403]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"14273","type":"Disease","text":["hallucinations"],"offsets":[[405,419]],"normalized":[{"db_name":"MESH","db_id":"D006212"}]},{"id":"14274","type":"Disease","text":["violent behavior"],"offsets":[[425,441]],"normalized":[{"db_name":"MESH","db_id":"D001523"}]},{"id":"14275","type":"Chemical","text":["methamphetamine"],"offsets":[[467,482]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"14276","type":"Disease","text":["xerostomia"],"offsets":[[519,529]],"normalized":[{"db_name":"MESH","db_id":"D014987"}]},{"id":"14277","type":"Disease","text":["caries"],"offsets":[[539,545]],"normalized":[{"db_name":"MESH","db_id":"D003731"}]},{"id":"14278","type":"Disease","text":["meth mouth"],"offsets":[[548,558]],"normalized":[]},{"id":"14279","type":"Disease","text":["tooth wear"],"offsets":[[576,586]],"normalized":[{"db_name":"MESH","db_id":"D057085"}]},{"id":"14280","type":"Chemical","text":["methamphetamine"],"offsets":[[626,641]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"14281","type":"Disease","text":["pain"],"offsets":[[732,736]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"14282","type":"Disease","text":["bad breath"],"offsets":[[738,748]],"normalized":[{"db_name":"MESH","db_id":"D012120"}]},{"id":"14283","type":"Disease","text":["carious lesions"],"offsets":[[903,918]],"normalized":[{"db_name":"MESH","db_id":"D003731"}]},{"id":"14284","type":"Chemical","text":["methamphetamine"],"offsets":[[990,1005]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"14285","type":"Disease","text":["carious episodes"],"offsets":[[1055,1071]],"normalized":[{"db_name":"MESH","db_id":"D003731"}]},{"id":"14286","type":"Disease","text":["meth mouth"],"offsets":[[1229,1239]],"normalized":[]},{"id":"14287","type":"Disease","text":["meth mouth"],"offsets":[[1510,1520]],"normalized":[]},{"id":"14288","type":"Chemical","text":["methamphetamines"],"offsets":[[1613,1629]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]}],"events":[],"coreferences":[],"relations":[{"id":"14289","type":"CID","arg1_id":"14270","arg2_id":"14277","normalized":[]},{"id":"14290","type":"CID","arg1_id":"14270","arg2_id":"14283","normalized":[]},{"id":"14291","type":"CID","arg1_id":"14270","arg2_id":"14285","normalized":[]},{"id":"14292","type":"CID","arg1_id":"14275","arg2_id":"14277","normalized":[]},{"id":"14293","type":"CID","arg1_id":"14275","arg2_id":"14283","normalized":[]},{"id":"14294","type":"CID","arg1_id":"14275","arg2_id":"14285","normalized":[]},{"id":"14295","type":"CID","arg1_id":"14280","arg2_id":"14277","normalized":[]},{"id":"14296","type":"CID","arg1_id":"14280","arg2_id":"14283","normalized":[]},{"id":"14297","type":"CID","arg1_id":"14280","arg2_id":"14285","normalized":[]},{"id":"14298","type":"CID","arg1_id":"14284","arg2_id":"14277","normalized":[]},{"id":"14299","type":"CID","arg1_id":"14284","arg2_id":"14283","normalized":[]},{"id":"14300","type":"CID","arg1_id":"14284","arg2_id":"14285","normalized":[]},{"id":"14301","type":"CID","arg1_id":"14288","arg2_id":"14277","normalized":[]},{"id":"14302","type":"CID","arg1_id":"14288","arg2_id":"14283","normalized":[]},{"id":"14303","type":"CID","arg1_id":"14288","arg2_id":"14285","normalized":[]}]}
{"id":"14304","document_id":"9653867","passages":[{"id":"14305","type":"title","text":["Thyroxine abuse: an unusual case of thyrotoxicosis in pregnancy."],"offsets":[[0,64]]},{"id":"14306","type":"abstract","text":["Eating disorders and the associated behavioural problems and drug abuse are uncommon in pregnancy. When they do occur they are often unrecognized because of denial but when significant may pose a risk to both the mother and her fetus. This case illustrates a number of problems that may be encountered in women with eating disorders in pregnancy, including prolonged and recurrent metabolic disturbances and diuretic abuse. In particular it illustrates the derangements of thyroid function seen in pregnant women with eating disorders and reminds us that when a cause for thyrotoxicosis remains obscure, thyroxine abuse should be considered and explored."],"offsets":[[65,719]]}],"entities":[{"id":"14307","type":"Chemical","text":["Thyroxine"],"offsets":[[0,9]],"normalized":[{"db_name":"MESH","db_id":"D013974"}]},{"id":"14308","type":"Disease","text":["thyrotoxicosis"],"offsets":[[36,50]],"normalized":[{"db_name":"MESH","db_id":"D013971"}]},{"id":"14309","type":"Disease","text":["Eating disorders"],"offsets":[[65,81]],"normalized":[{"db_name":"MESH","db_id":"D001068"}]},{"id":"14310","type":"Disease","text":["drug abuse"],"offsets":[[126,136]],"normalized":[{"db_name":"MESH","db_id":"D019966"}]},{"id":"14311","type":"Disease","text":["eating disorders"],"offsets":[[381,397]],"normalized":[{"db_name":"MESH","db_id":"D001068"}]},{"id":"14312","type":"Disease","text":["eating disorders"],"offsets":[[583,599]],"normalized":[{"db_name":"MESH","db_id":"D001068"}]},{"id":"14313","type":"Disease","text":["thyrotoxicosis"],"offsets":[[637,651]],"normalized":[{"db_name":"MESH","db_id":"D013971"}]},{"id":"14314","type":"Chemical","text":["thyroxine"],"offsets":[[669,678]],"normalized":[{"db_name":"MESH","db_id":"D013974"}]}],"events":[],"coreferences":[],"relations":[{"id":"14315","type":"CID","arg1_id":"14307","arg2_id":"14308","normalized":[]},{"id":"14316","type":"CID","arg1_id":"14307","arg2_id":"14313","normalized":[]},{"id":"14317","type":"CID","arg1_id":"14314","arg2_id":"14308","normalized":[]},{"id":"14318","type":"CID","arg1_id":"14314","arg2_id":"14313","normalized":[]}]}
{"id":"14319","document_id":"17608141","passages":[{"id":"14320","type":"title","text":["Attenuation of methamphetamine-induced nigrostriatal dopaminergic neurotoxicity in mice by lipopolysaccharide pretreatment."],"offsets":[[0,123]]},{"id":"14321","type":"abstract","text":["Immunological activation has been proposed to play a role in methamphetamine-induced dopaminergic terminal damage. In this study, we examined the roles of lipopolysaccharide, a pro-inflammatory and inflammatory factor, treatment in modulating the methamphetamine-induced nigrostriatal dopamine neurotoxicity. Lipopolysaccharide pretreatment did not affect the basal body temperature or methamphetamine-elicited hyperthermia three days later. Such systemic lipopolysaccharide treatment mitigated methamphetamine-induced striatal dopamine and 3,4-dihydroxyphenylacetic acid depletions in a dose-dependent manner. As the most potent dose (1 mg\/kg) of lipopolysaccharide was administered two weeks, one day before or after the methamphetamine dosing regimen, methamphetamine-induced striatal dopamine and 3,4-dihydroxyphenylacetic acid depletions remained unaltered. Moreover, systemic lipopolysaccharide pretreatment (1 mg\/kg) attenuated local methamphetamine infusion-produced dopamine and 3,4-dihydroxyphenylacetic acid depletions in the striatum, indicating that the protective effect of lipopolysaccharide is less likely due to interrupted peripheral distribution or metabolism of methamphetamine. We concluded a critical time window for systemic lipopolysaccharide pretreatment in exerting effective protection against methamphetamine-induced nigrostriatal dopamine neurotoxicity."],"offsets":[[124,1506]]}],"entities":[{"id":"14322","type":"Chemical","text":["methamphetamine"],"offsets":[[15,30]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"14323","type":"Disease","text":["neurotoxicity"],"offsets":[[66,79]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"14324","type":"Chemical","text":["lipopolysaccharide"],"offsets":[[91,109]],"normalized":[{"db_name":"MESH","db_id":"D008070"}]},{"id":"14325","type":"Chemical","text":["methamphetamine"],"offsets":[[185,200]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"14326","type":"Disease","text":["dopaminergic terminal damage"],"offsets":[[209,237]],"normalized":[{"db_name":"MESH","db_id":"D009422"}]},{"id":"14327","type":"Chemical","text":["lipopolysaccharide"],"offsets":[[279,297]],"normalized":[{"db_name":"MESH","db_id":"D008070"}]},{"id":"14328","type":"Chemical","text":["methamphetamine"],"offsets":[[371,386]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"14329","type":"Chemical","text":["dopamine"],"offsets":[[409,417]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"14330","type":"Disease","text":["neurotoxicity"],"offsets":[[418,431]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"14331","type":"Chemical","text":["Lipopolysaccharide"],"offsets":[[433,451]],"normalized":[{"db_name":"MESH","db_id":"D008070"}]},{"id":"14332","type":"Chemical","text":["methamphetamine"],"offsets":[[510,525]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"14333","type":"Disease","text":["hyperthermia"],"offsets":[[535,547]],"normalized":[{"db_name":"MESH","db_id":"D005334"}]},{"id":"14334","type":"Chemical","text":["lipopolysaccharide"],"offsets":[[580,598]],"normalized":[{"db_name":"MESH","db_id":"D008070"}]},{"id":"14335","type":"Chemical","text":["methamphetamine"],"offsets":[[619,634]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"14336","type":"Chemical","text":["dopamine"],"offsets":[[652,660]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"14337","type":"Chemical","text":["3,4-dihydroxyphenylacetic acid"],"offsets":[[665,695]],"normalized":[{"db_name":"MESH","db_id":"D015102"}]},{"id":"14338","type":"Chemical","text":["lipopolysaccharide"],"offsets":[[772,790]],"normalized":[{"db_name":"MESH","db_id":"D008070"}]},{"id":"14339","type":"Chemical","text":["methamphetamine"],"offsets":[[847,862]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"14340","type":"Chemical","text":["methamphetamine"],"offsets":[[879,894]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"14341","type":"Chemical","text":["dopamine"],"offsets":[[912,920]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"14342","type":"Chemical","text":["3,4-dihydroxyphenylacetic acid"],"offsets":[[925,955]],"normalized":[{"db_name":"MESH","db_id":"D015102"}]},{"id":"14343","type":"Chemical","text":["lipopolysaccharide"],"offsets":[[1006,1024]],"normalized":[{"db_name":"MESH","db_id":"D008070"}]},{"id":"14344","type":"Chemical","text":["methamphetamine"],"offsets":[[1065,1080]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"14345","type":"Chemical","text":["dopamine"],"offsets":[[1099,1107]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"14346","type":"Chemical","text":["3,4-dihydroxyphenylacetic acid"],"offsets":[[1112,1142]],"normalized":[{"db_name":"MESH","db_id":"D015102"}]},{"id":"14347","type":"Chemical","text":["lipopolysaccharide"],"offsets":[[1212,1230]],"normalized":[{"db_name":"MESH","db_id":"D008070"}]},{"id":"14348","type":"Chemical","text":["methamphetamine"],"offsets":[[1306,1321]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"14349","type":"Chemical","text":["lipopolysaccharide"],"offsets":[[1372,1390]],"normalized":[{"db_name":"MESH","db_id":"D008070"}]},{"id":"14350","type":"Chemical","text":["methamphetamine"],"offsets":[[1445,1460]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"14351","type":"Chemical","text":["dopamine"],"offsets":[[1483,1491]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"14352","type":"Disease","text":["neurotoxicity"],"offsets":[[1492,1505]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]}],"events":[],"coreferences":[],"relations":[{"id":"14353","type":"CID","arg1_id":"14322","arg2_id":"14333","normalized":[]},{"id":"14354","type":"CID","arg1_id":"14325","arg2_id":"14333","normalized":[]},{"id":"14355","type":"CID","arg1_id":"14328","arg2_id":"14333","normalized":[]},{"id":"14356","type":"CID","arg1_id":"14332","arg2_id":"14333","normalized":[]},{"id":"14357","type":"CID","arg1_id":"14335","arg2_id":"14333","normalized":[]},{"id":"14358","type":"CID","arg1_id":"14339","arg2_id":"14333","normalized":[]},{"id":"14359","type":"CID","arg1_id":"14340","arg2_id":"14333","normalized":[]},{"id":"14360","type":"CID","arg1_id":"14344","arg2_id":"14333","normalized":[]},{"id":"14361","type":"CID","arg1_id":"14348","arg2_id":"14333","normalized":[]},{"id":"14362","type":"CID","arg1_id":"14350","arg2_id":"14333","normalized":[]}]}
{"id":"14363","document_id":"2559236","passages":[{"id":"14364","type":"title","text":["Effect of converting enzyme inhibition on the course of adriamycin-induced nephropathy."],"offsets":[[0,87]]},{"id":"14365","type":"abstract","text":["The effect of the converting enzyme inhibitor (CEI) enalapril was assessed in Munich-Wistar rats with established adriamycin nephrosis. Rats were given a single dose of adriamycin and one month later divided into four groups matched for albuminuria, blood pressure, and plasma albumin concentration. Groups 1 and 3 remained untreated while groups 2 and 4 received enalapril. Groups 1 and 2 underwent micropuncture studies after 10 days. These short-term studies showed that enalapril reduced arterial blood pressure (101 +\/- 2 vs. 124 +\/- 3 mm Hg, group 2 vs. 1, P less than 0.05) and glomerular capillary pressure (54 +\/- 1 vs. 61 +\/- 2 mm Hg, P less than 0.05) without reducing albuminuria (617 +\/- 50 vs. 570 +\/- 47 mg\/day) or GFR (1.03 +\/- 0.04 vs. 1.04 +\/- 0.11 ml\/min). Groups 3 and 4 were studied at four and at six months to assess the effect of enalapril on progression of renal injury in adriamycin nephrosis. Chronic enalapril treatment reduced blood pressure without reducing albuminuria in group 4. Untreated group 3 rats exhibited a progressive reduction in GFR (0.35 +\/- 0.08 ml\/min at 4 months, 0.27 +\/- 0.07 ml\/min at 6 months). Enalapril treatment blunted but did not prevent reduction in GFR in group 4 (0.86 +\/- 0.15 ml\/min at 4 months, 0.69 +\/- 0.13 ml\/min at 6 months, both P less than 0.05 vs. group 3). Reduction in GFR was associated with the development of glomerular sclerosis in both treated and untreated rats.(ABSTRACT TRUNCATED AT 250 WORDS)"],"offsets":[[88,1560]]}],"entities":[{"id":"14366","type":"Chemical","text":["adriamycin"],"offsets":[[56,66]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"14367","type":"Disease","text":["nephropathy"],"offsets":[[75,86]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"14368","type":"Chemical","text":["enalapril"],"offsets":[[140,149]],"normalized":[{"db_name":"MESH","db_id":"D004656"}]},{"id":"14369","type":"Chemical","text":["adriamycin"],"offsets":[[202,212]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"14370","type":"Disease","text":["nephrosis"],"offsets":[[213,222]],"normalized":[{"db_name":"MESH","db_id":"D009401"}]},{"id":"14371","type":"Chemical","text":["adriamycin"],"offsets":[[257,267]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"14372","type":"Disease","text":["albuminuria"],"offsets":[[325,336]],"normalized":[{"db_name":"MESH","db_id":"D000419"}]},{"id":"14373","type":"Chemical","text":["enalapril"],"offsets":[[452,461]],"normalized":[{"db_name":"MESH","db_id":"D004656"}]},{"id":"14374","type":"Chemical","text":["enalapril"],"offsets":[[562,571]],"normalized":[{"db_name":"MESH","db_id":"D004656"}]},{"id":"14375","type":"Disease","text":["albuminuria"],"offsets":[[768,779]],"normalized":[{"db_name":"MESH","db_id":"D000419"}]},{"id":"14376","type":"Chemical","text":["enalapril"],"offsets":[[942,951]],"normalized":[{"db_name":"MESH","db_id":"D004656"}]},{"id":"14377","type":"Disease","text":["renal injury"],"offsets":[[970,982]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"14378","type":"Chemical","text":["adriamycin"],"offsets":[[986,996]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"14379","type":"Disease","text":["nephrosis"],"offsets":[[997,1006]],"normalized":[{"db_name":"MESH","db_id":"D009401"}]},{"id":"14380","type":"Chemical","text":["enalapril"],"offsets":[[1016,1025]],"normalized":[{"db_name":"MESH","db_id":"D004656"}]},{"id":"14381","type":"Disease","text":["albuminuria"],"offsets":[[1076,1087]],"normalized":[{"db_name":"MESH","db_id":"D000419"}]},{"id":"14382","type":"Chemical","text":["Enalapril"],"offsets":[[1234,1243]],"normalized":[{"db_name":"MESH","db_id":"D004656"}]},{"id":"14383","type":"Disease","text":["glomerular sclerosis"],"offsets":[[1471,1491]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]}],"events":[],"coreferences":[],"relations":[{"id":"14384","type":"CID","arg1_id":"14366","arg2_id":"14372","normalized":[]},{"id":"14385","type":"CID","arg1_id":"14366","arg2_id":"14375","normalized":[]},{"id":"14386","type":"CID","arg1_id":"14366","arg2_id":"14381","normalized":[]},{"id":"14387","type":"CID","arg1_id":"14369","arg2_id":"14372","normalized":[]},{"id":"14388","type":"CID","arg1_id":"14369","arg2_id":"14375","normalized":[]},{"id":"14389","type":"CID","arg1_id":"14369","arg2_id":"14381","normalized":[]},{"id":"14390","type":"CID","arg1_id":"14371","arg2_id":"14372","normalized":[]},{"id":"14391","type":"CID","arg1_id":"14371","arg2_id":"14375","normalized":[]},{"id":"14392","type":"CID","arg1_id":"14371","arg2_id":"14381","normalized":[]},{"id":"14393","type":"CID","arg1_id":"14378","arg2_id":"14372","normalized":[]},{"id":"14394","type":"CID","arg1_id":"14378","arg2_id":"14375","normalized":[]},{"id":"14395","type":"CID","arg1_id":"14378","arg2_id":"14381","normalized":[]},{"id":"14396","type":"CID","arg1_id":"14366","arg2_id":"14370","normalized":[]},{"id":"14397","type":"CID","arg1_id":"14366","arg2_id":"14379","normalized":[]},{"id":"14398","type":"CID","arg1_id":"14369","arg2_id":"14370","normalized":[]},{"id":"14399","type":"CID","arg1_id":"14369","arg2_id":"14379","normalized":[]},{"id":"14400","type":"CID","arg1_id":"14371","arg2_id":"14370","normalized":[]},{"id":"14401","type":"CID","arg1_id":"14371","arg2_id":"14379","normalized":[]},{"id":"14402","type":"CID","arg1_id":"14378","arg2_id":"14370","normalized":[]},{"id":"14403","type":"CID","arg1_id":"14378","arg2_id":"14379","normalized":[]}]}
{"id":"14404","document_id":"21029050","passages":[{"id":"14405","type":"title","text":["Butyrylcholinesterase gene mutations in patients with prolonged apnea after succinylcholine for electroconvulsive therapy."],"offsets":[[0,122]]},{"id":"14406","type":"abstract","text":["BACKGROUND: patients undergoing electroconvulsive therapy (ECT) often receive succinylcholine as part of the anesthetic procedure. The duration of action may be prolonged in patients with genetic variants of the butyrylcholinesterase enzyme (BChE), the most common being the K- and the A-variants. The aim of the study was to assess the clinical significance of genetic variants in butyrylcholinesterase gene (BCHE) in patients with a suspected prolonged duration of action of succinylcholine after ECT. METHODS: a total of 13 patients were referred to the Danish Cholinesterase Research Unit after ECT during 38 months. We determined the BChE activity and the BCHE genotype using molecular genetic methods, the duration of apnea, time to sufficient spontaneous ventilation and whether neuromuscular monitoring was used. The duration of apnea was compared with published data on normal subjects. RESULTS: in 11 patients, mutations were found in the BCHE gene, the K-variant being the most frequent. The duration of apnea was 5-15 min compared with 3-5.3 min from the literature. Severe distress was noted in the recovery phase in two patients. Neuromuscular monitoring was used in two patients. CONCLUSION: eleven of 13 patients with a prolonged duration of action of succinylcholine had mutations in BCHE, indicating that this is the possible reason for a prolonged period of apnea. We recommend objective neuromuscular monitoring during the first ECT."],"offsets":[[123,1576]]}],"entities":[{"id":"14407","type":"Disease","text":["apnea"],"offsets":[[64,69]],"normalized":[{"db_name":"MESH","db_id":"D001049"}]},{"id":"14408","type":"Chemical","text":["succinylcholine"],"offsets":[[76,91]],"normalized":[{"db_name":"MESH","db_id":"D013390"}]},{"id":"14409","type":"Chemical","text":["succinylcholine"],"offsets":[[201,216]],"normalized":[{"db_name":"MESH","db_id":"D013390"}]},{"id":"14410","type":"Chemical","text":["succinylcholine"],"offsets":[[600,615]],"normalized":[{"db_name":"MESH","db_id":"D013390"}]},{"id":"14411","type":"Disease","text":["apnea"],"offsets":[[847,852]],"normalized":[{"db_name":"MESH","db_id":"D001049"}]},{"id":"14412","type":"Disease","text":["apnea"],"offsets":[[960,965]],"normalized":[{"db_name":"MESH","db_id":"D001049"}]},{"id":"14413","type":"Disease","text":["apnea"],"offsets":[[1138,1143]],"normalized":[{"db_name":"MESH","db_id":"D001049"}]},{"id":"14414","type":"Chemical","text":["succinylcholine"],"offsets":[[1391,1406]],"normalized":[{"db_name":"MESH","db_id":"D013390"}]},{"id":"14415","type":"Disease","text":["apnea"],"offsets":[[1500,1505]],"normalized":[{"db_name":"MESH","db_id":"D001049"}]}],"events":[],"coreferences":[],"relations":[{"id":"14416","type":"CID","arg1_id":"14408","arg2_id":"14407","normalized":[]},{"id":"14417","type":"CID","arg1_id":"14408","arg2_id":"14411","normalized":[]},{"id":"14418","type":"CID","arg1_id":"14408","arg2_id":"14412","normalized":[]},{"id":"14419","type":"CID","arg1_id":"14408","arg2_id":"14413","normalized":[]},{"id":"14420","type":"CID","arg1_id":"14408","arg2_id":"14415","normalized":[]},{"id":"14421","type":"CID","arg1_id":"14409","arg2_id":"14407","normalized":[]},{"id":"14422","type":"CID","arg1_id":"14409","arg2_id":"14411","normalized":[]},{"id":"14423","type":"CID","arg1_id":"14409","arg2_id":"14412","normalized":[]},{"id":"14424","type":"CID","arg1_id":"14409","arg2_id":"14413","normalized":[]},{"id":"14425","type":"CID","arg1_id":"14409","arg2_id":"14415","normalized":[]},{"id":"14426","type":"CID","arg1_id":"14410","arg2_id":"14407","normalized":[]},{"id":"14427","type":"CID","arg1_id":"14410","arg2_id":"14411","normalized":[]},{"id":"14428","type":"CID","arg1_id":"14410","arg2_id":"14412","normalized":[]},{"id":"14429","type":"CID","arg1_id":"14410","arg2_id":"14413","normalized":[]},{"id":"14430","type":"CID","arg1_id":"14410","arg2_id":"14415","normalized":[]},{"id":"14431","type":"CID","arg1_id":"14414","arg2_id":"14407","normalized":[]},{"id":"14432","type":"CID","arg1_id":"14414","arg2_id":"14411","normalized":[]},{"id":"14433","type":"CID","arg1_id":"14414","arg2_id":"14412","normalized":[]},{"id":"14434","type":"CID","arg1_id":"14414","arg2_id":"14413","normalized":[]},{"id":"14435","type":"CID","arg1_id":"14414","arg2_id":"14415","normalized":[]}]}
{"id":"14436","document_id":"10901305","passages":[{"id":"14437","type":"title","text":["Ketamine sedation for the reduction of children's fractures in the emergency department."],"offsets":[[0,88]]},{"id":"14438","type":"abstract","text":["BACKGROUND: There recently has been a resurgence in the utilization of ketamine, a unique anesthetic, for emergency-department procedures requiring sedation. The purpose of the present study was to examine the safety and efficacy of ketamine for sedation in the treatment of children's fractures in the emergency department. METHODS: One hundred and fourteen children (average age, 5.3 years; range, twelve months to ten years and ten months) who underwent closed reduction of an isolated fracture or dislocation in the emergency department at a level-I trauma center were prospectively evaluated. Ketamine hydrochloride was administered intravenously (at a dose of two milligrams per kilogram of body weight) in ninety-nine of the patients and intramuscularly (at a dose of four milligrams per kilogram of body weight) in the other fifteen. A board-certified emergency physician skilled in airway management supervised administration of the anesthetic, and the patients were monitored by a registered nurse. Any pain during the reduction was rated by the orthopaedic surgeon treating the patient according to the Children's Hospital of Eastern Ontario Pain Scale (CHEOPS). RESULTS: The average time from intravenous administration of ketamine to manipulation of the fracture or dislocation was one minute and thirty-six seconds (range, twenty seconds to five minutes), and the average time from intramuscular administration to manipulation was four minutes and forty-two seconds (range, sixty seconds to fifteen minutes). The average score according to the Children's Hospital of Eastern Ontario Pain Scale was 6.4 points (range, 5 to 10 points), reflecting minimal or no pain during fracture reduction. Adequate fracture reduction was obtained in 111 of the children. Ninety-nine percent (sixty-eight) of the sixty-nine parents present during the reduction were pleased with the sedation and would allow it to be used again in a similar situation. Patency of the airway and independent respiration were maintained in all of the patients. Blood pressure and heart rate remained stable. Minor side effects included nausea (thirteen patients), emesis (eight of the thirteen patients with nausea), clumsiness (evident as ataxic movements in ten patients), and dysphoric reaction (one patient). No long-term sequelae were noted, and no patients had hallucinations or nightmares. CONCLUSIONS: Ketamine reliably, safely, and quickly provided adequate sedation to effectively facilitate the reduction of children's fractures in the emergency department at our institution. Ketamine should only be used in an environment such as the emergency department, where proper one-on-one monitoring is used and board-certified physicians skilled in airway management are directly involved in the care of the patient."],"offsets":[[89,2889]]}],"entities":[{"id":"14439","type":"Chemical","text":["Ketamine"],"offsets":[[0,8]],"normalized":[{"db_name":"MESH","db_id":"D007649"}]},{"id":"14440","type":"Disease","text":["fractures"],"offsets":[[50,59]],"normalized":[{"db_name":"MESH","db_id":"D050723"}]},{"id":"14441","type":"Chemical","text":["ketamine"],"offsets":[[160,168]],"normalized":[{"db_name":"MESH","db_id":"D007649"}]},{"id":"14442","type":"Chemical","text":["ketamine"],"offsets":[[322,330]],"normalized":[{"db_name":"MESH","db_id":"D007649"}]},{"id":"14443","type":"Disease","text":["fractures"],"offsets":[[375,384]],"normalized":[{"db_name":"MESH","db_id":"D050723"}]},{"id":"14444","type":"Disease","text":["fracture"],"offsets":[[578,586]],"normalized":[{"db_name":"MESH","db_id":"D050723"}]},{"id":"14445","type":"Disease","text":["dislocation"],"offsets":[[590,601]],"normalized":[{"db_name":"MESH","db_id":"D004204"}]},{"id":"14446","type":"Disease","text":["trauma"],"offsets":[[643,649]],"normalized":[{"db_name":"MESH","db_id":"D014947"}]},{"id":"14447","type":"Chemical","text":["Ketamine hydrochloride"],"offsets":[[687,709]],"normalized":[{"db_name":"MESH","db_id":"D007649"}]},{"id":"14448","type":"Disease","text":["pain"],"offsets":[[1102,1106]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"14449","type":"Disease","text":["Pain"],"offsets":[[1242,1246]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"14450","type":"Chemical","text":["ketamine"],"offsets":[[1324,1332]],"normalized":[{"db_name":"MESH","db_id":"D007649"}]},{"id":"14451","type":"Disease","text":["fracture"],"offsets":[[1356,1364]],"normalized":[{"db_name":"MESH","db_id":"D050723"}]},{"id":"14452","type":"Disease","text":["dislocation"],"offsets":[[1368,1379]],"normalized":[{"db_name":"MESH","db_id":"D004204"}]},{"id":"14453","type":"Disease","text":["Pain"],"offsets":[[1686,1690]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"14454","type":"Disease","text":["pain"],"offsets":[[1762,1766]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"14455","type":"Disease","text":["fracture"],"offsets":[[1774,1782]],"normalized":[{"db_name":"MESH","db_id":"D050723"}]},{"id":"14456","type":"Disease","text":["fracture"],"offsets":[[1803,1811]],"normalized":[{"db_name":"MESH","db_id":"D050723"}]},{"id":"14457","type":"Disease","text":["nausea"],"offsets":[[2204,2210]],"normalized":[{"db_name":"MESH","db_id":"D009325"}]},{"id":"14458","type":"Disease","text":["emesis"],"offsets":[[2232,2238]],"normalized":[{"db_name":"MESH","db_id":"D014839"}]},{"id":"14459","type":"Disease","text":["nausea"],"offsets":[[2276,2282]],"normalized":[{"db_name":"MESH","db_id":"D009325"}]},{"id":"14460","type":"Disease","text":["clumsiness"],"offsets":[[2285,2295]],"normalized":[{"db_name":"MESH","db_id":"D001259"}]},{"id":"14461","type":"Disease","text":["ataxic movements"],"offsets":[[2308,2324]],"normalized":[{"db_name":"MESH","db_id":"D001259"}]},{"id":"14462","type":"Disease","text":["dysphoric reaction"],"offsets":[[2347,2365]],"normalized":[]},{"id":"14463","type":"Disease","text":["hallucinations"],"offsets":[[2435,2449]],"normalized":[{"db_name":"MESH","db_id":"D006212"}]},{"id":"14464","type":"Chemical","text":["Ketamine"],"offsets":[[2478,2486]],"normalized":[{"db_name":"MESH","db_id":"D007649"}]},{"id":"14465","type":"Disease","text":["fractures"],"offsets":[[2598,2607]],"normalized":[{"db_name":"MESH","db_id":"D050723"}]},{"id":"14466","type":"Chemical","text":["Ketamine"],"offsets":[[2656,2664]],"normalized":[{"db_name":"MESH","db_id":"D007649"}]}],"events":[],"coreferences":[],"relations":[{"id":"14467","type":"CID","arg1_id":"14439","arg2_id":"14457","normalized":[]},{"id":"14468","type":"CID","arg1_id":"14439","arg2_id":"14459","normalized":[]},{"id":"14469","type":"CID","arg1_id":"14441","arg2_id":"14457","normalized":[]},{"id":"14470","type":"CID","arg1_id":"14441","arg2_id":"14459","normalized":[]},{"id":"14471","type":"CID","arg1_id":"14442","arg2_id":"14457","normalized":[]},{"id":"14472","type":"CID","arg1_id":"14442","arg2_id":"14459","normalized":[]},{"id":"14473","type":"CID","arg1_id":"14447","arg2_id":"14457","normalized":[]},{"id":"14474","type":"CID","arg1_id":"14447","arg2_id":"14459","normalized":[]},{"id":"14475","type":"CID","arg1_id":"14450","arg2_id":"14457","normalized":[]},{"id":"14476","type":"CID","arg1_id":"14450","arg2_id":"14459","normalized":[]},{"id":"14477","type":"CID","arg1_id":"14464","arg2_id":"14457","normalized":[]},{"id":"14478","type":"CID","arg1_id":"14464","arg2_id":"14459","normalized":[]},{"id":"14479","type":"CID","arg1_id":"14466","arg2_id":"14457","normalized":[]},{"id":"14480","type":"CID","arg1_id":"14466","arg2_id":"14459","normalized":[]},{"id":"14481","type":"CID","arg1_id":"14439","arg2_id":"14458","normalized":[]},{"id":"14482","type":"CID","arg1_id":"14441","arg2_id":"14458","normalized":[]},{"id":"14483","type":"CID","arg1_id":"14442","arg2_id":"14458","normalized":[]},{"id":"14484","type":"CID","arg1_id":"14447","arg2_id":"14458","normalized":[]},{"id":"14485","type":"CID","arg1_id":"14450","arg2_id":"14458","normalized":[]},{"id":"14486","type":"CID","arg1_id":"14464","arg2_id":"14458","normalized":[]},{"id":"14487","type":"CID","arg1_id":"14466","arg2_id":"14458","normalized":[]},{"id":"14488","type":"CID","arg1_id":"14439","arg2_id":"14460","normalized":[]},{"id":"14489","type":"CID","arg1_id":"14439","arg2_id":"14461","normalized":[]},{"id":"14490","type":"CID","arg1_id":"14441","arg2_id":"14460","normalized":[]},{"id":"14491","type":"CID","arg1_id":"14441","arg2_id":"14461","normalized":[]},{"id":"14492","type":"CID","arg1_id":"14442","arg2_id":"14460","normalized":[]},{"id":"14493","type":"CID","arg1_id":"14442","arg2_id":"14461","normalized":[]},{"id":"14494","type":"CID","arg1_id":"14447","arg2_id":"14460","normalized":[]},{"id":"14495","type":"CID","arg1_id":"14447","arg2_id":"14461","normalized":[]},{"id":"14496","type":"CID","arg1_id":"14450","arg2_id":"14460","normalized":[]},{"id":"14497","type":"CID","arg1_id":"14450","arg2_id":"14461","normalized":[]},{"id":"14498","type":"CID","arg1_id":"14464","arg2_id":"14460","normalized":[]},{"id":"14499","type":"CID","arg1_id":"14464","arg2_id":"14461","normalized":[]},{"id":"14500","type":"CID","arg1_id":"14466","arg2_id":"14460","normalized":[]},{"id":"14501","type":"CID","arg1_id":"14466","arg2_id":"14461","normalized":[]}]}
{"id":"14502","document_id":"19037603","passages":[{"id":"14503","type":"title","text":["Prophylactic use of lamivudine with chronic immunosuppressive therapy for rheumatologic disorders."],"offsets":[[0,98]]},{"id":"14504","type":"abstract","text":["The objective of this study was to report our experience concerning the effectiveness of the prophylactic administration of lamivudine in hepatitis B virus surface antigen (HBs Ag) positive patients with rheumatologic disease. From June 2004 to October 2006, 11 HBs Ag positive patients with rheumatologic diseases, who were on both immunosuppressive and prophylactic lamivudine therapies, were retrospectively assessed. Liver function tests, hepatitis B virus (HBV) serologic markers, and HBV DNA levels of the patients during follow-up were obtained from hospital file records. Eleven patients (six male) with median age 47 years (range 27-73), median disease duration 50 months (range 9-178) and median follow-up period of patients 13.8 months (range 5-27) were enrolled in this study. Lamivudine therapy was started 3-7 days prior to immunosuppressive therapy in all patients. Baseline, liver function tests were elevated in two patients (fourth patient: ALT:122 IU\/l, AST:111 IU\/l, tenth patient:ALT:294 IU\/l, AST:274 IU\/l, with minimal changes in the liver biopsy in both). Shortly after treatment their tests normalized and during follow-up period none of the patients had abnormal liver function tests. In four patients HBV DNA levels were higher than normal at baseline. Two of these normalized and the others increased later. In three additional patients, HBV DNA levels were increased during follow-up. None of the patients had significant clinical sings of HBV activation. Lamivudine was well tolerated and was continued in all patients. Prophylactic administration of lamivudine in patients who required immunosuppressive therapy seems to be safe, well tolerated and effective in preventing HBV reactivation."],"offsets":[[99,1820]]}],"entities":[{"id":"14505","type":"Chemical","text":["lamivudine"],"offsets":[[20,30]],"normalized":[{"db_name":"MESH","db_id":"D019259"}]},{"id":"14506","type":"Disease","text":["rheumatologic disorders"],"offsets":[[74,97]],"normalized":[{"db_name":"MESH","db_id":"D012216"}]},{"id":"14507","type":"Chemical","text":["lamivudine"],"offsets":[[223,233]],"normalized":[{"db_name":"MESH","db_id":"D019259"}]},{"id":"14508","type":"Chemical","text":["hepatitis B virus surface antigen"],"offsets":[[237,270]],"normalized":[{"db_name":"MESH","db_id":"D006514"}]},{"id":"14509","type":"Chemical","text":["HBs Ag"],"offsets":[[272,278]],"normalized":[{"db_name":"MESH","db_id":"D006514"}]},{"id":"14510","type":"Disease","text":["rheumatologic disease"],"offsets":[[303,324]],"normalized":[{"db_name":"MESH","db_id":"D012216"}]},{"id":"14511","type":"Chemical","text":["HBs Ag"],"offsets":[[361,367]],"normalized":[{"db_name":"MESH","db_id":"D006514"}]},{"id":"14512","type":"Disease","text":["rheumatologic diseases"],"offsets":[[391,413]],"normalized":[{"db_name":"MESH","db_id":"D012216"}]},{"id":"14513","type":"Chemical","text":["lamivudine"],"offsets":[[467,477]],"normalized":[{"db_name":"MESH","db_id":"D019259"}]},{"id":"14514","type":"Disease","text":["hepatitis B"],"offsets":[[542,553]],"normalized":[{"db_name":"MESH","db_id":"D006509"}]},{"id":"14515","type":"Chemical","text":["Lamivudine"],"offsets":[[888,898]],"normalized":[{"db_name":"MESH","db_id":"D019259"}]},{"id":"14516","type":"Disease","text":["abnormal liver function"],"offsets":[[1279,1302]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"14517","type":"Chemical","text":["Lamivudine"],"offsets":[[1584,1594]],"normalized":[{"db_name":"MESH","db_id":"D019259"}]},{"id":"14518","type":"Chemical","text":["lamivudine"],"offsets":[[1680,1690]],"normalized":[{"db_name":"MESH","db_id":"D019259"}]}],"events":[],"coreferences":[],"relations":[{"id":"14519","type":"CID","arg1_id":"14508","arg2_id":"14514","normalized":[]},{"id":"14520","type":"CID","arg1_id":"14509","arg2_id":"14514","normalized":[]},{"id":"14521","type":"CID","arg1_id":"14511","arg2_id":"14514","normalized":[]}]}
{"id":"14522","document_id":"20084309","passages":[{"id":"14523","type":"title","text":["Safety of transesophageal echocardiography in adults: study in a multidisciplinary hospital."],"offsets":[[0,92]]},{"id":"14524","type":"abstract","text":["BACKGROUND: TEE is a semi-invasive tool broadly used and its utilization associated to sedatives drugs might to affect the procedure safety. OBJECTIVE: to analyze aspects of TEE safety associated to the use of Midazolan (MZ) and Flumazenil (FL) and the influence of the clinical variables on the event rate. METHOD: prospective study with 137 patients that underwent TEE with MZ associated to moderate sedation. We analyzed the following events: complications related with the topical anesthesia, with MZ use and with the procedure. Uni- and multivariate analyses were used to test the influence of the clinical variables: age, sex, stroke, myocardiopathy (MP), duration of the test, mitral regurgitation (MR) and the MZ dose. RESULTS: All patients (65+\/-16 yrs; 58% males) finished the examination. The mean doses of MZ and FL were 4.3+\/-1.9 mg and 0.28+\/-0.2 mg, respectively. The duration of the examination and the mean ejection fraction (EF) were 16.4+\/-6.1 minutes and 60+\/-9%, respectively. Mild hypoxia (SO2<90%) was the most common event (11 patients); 3 patients (2%) presented transient hypoxia due to upper airway obstruction by probe introduction and 8 (5.8%) due to hypoxia caused by MZ use. Transient hypotension (SAP<90mmHg) occurred in 1 patient (0.7%). The multivariate analysis showed that severe MR, MP (EF<45%) and high doses of MZ (>5mg) were associated with events (p<0.001). The EF was 40%, in the group with MP and 44% in the group with severe MR and it can be a factor associated with clinical events in the last group. CONCLUSION: TEE with sedation presents a low rate of events. There were no severe events and there was no need to interrupt the examinations."],"offsets":[[93,1780]]}],"entities":[{"id":"14525","type":"Chemical","text":["Midazolan"],"offsets":[[303,312]],"normalized":[{"db_name":"MESH","db_id":"D008874"}]},{"id":"14526","type":"Chemical","text":["MZ"],"offsets":[[314,316]],"normalized":[{"db_name":"MESH","db_id":"D008874"}]},{"id":"14527","type":"Chemical","text":["Flumazenil"],"offsets":[[322,332]],"normalized":[{"db_name":"MESH","db_id":"D005442"}]},{"id":"14528","type":"Chemical","text":["FL"],"offsets":[[334,336]],"normalized":[{"db_name":"MESH","db_id":"D005442"}]},{"id":"14529","type":"Chemical","text":["MZ"],"offsets":[[469,471]],"normalized":[{"db_name":"MESH","db_id":"D008874"}]},{"id":"14530","type":"Chemical","text":["MZ"],"offsets":[[595,597]],"normalized":[{"db_name":"MESH","db_id":"D008874"}]},{"id":"14531","type":"Disease","text":["stroke"],"offsets":[[726,732]],"normalized":[{"db_name":"MESH","db_id":"D020521"}]},{"id":"14532","type":"Disease","text":["myocardiopathy"],"offsets":[[734,748]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"14533","type":"Disease","text":["MP"],"offsets":[[750,752]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"14534","type":"Disease","text":["mitral regurgitation"],"offsets":[[777,797]],"normalized":[{"db_name":"MESH","db_id":"D008944"}]},{"id":"14535","type":"Disease","text":["MR"],"offsets":[[799,801]],"normalized":[{"db_name":"MESH","db_id":"D008944"}]},{"id":"14536","type":"Chemical","text":["MZ"],"offsets":[[811,813]],"normalized":[{"db_name":"MESH","db_id":"D008874"}]},{"id":"14537","type":"Chemical","text":["MZ"],"offsets":[[911,913]],"normalized":[{"db_name":"MESH","db_id":"D008874"}]},{"id":"14538","type":"Chemical","text":["FL"],"offsets":[[918,920]],"normalized":[{"db_name":"MESH","db_id":"D005442"}]},{"id":"14539","type":"Disease","text":["hypoxia"],"offsets":[[1096,1103]],"normalized":[{"db_name":"MESH","db_id":"D000860"}]},{"id":"14540","type":"Disease","text":["hypoxia"],"offsets":[[1191,1198]],"normalized":[{"db_name":"MESH","db_id":"D000860"}]},{"id":"14541","type":"Disease","text":["airway obstruction"],"offsets":[[1212,1230]],"normalized":[{"db_name":"MESH","db_id":"D000402"}]},{"id":"14542","type":"Disease","text":["hypoxia"],"offsets":[[1273,1280]],"normalized":[{"db_name":"MESH","db_id":"D000860"}]},{"id":"14543","type":"Chemical","text":["MZ"],"offsets":[[1291,1293]],"normalized":[{"db_name":"MESH","db_id":"D008874"}]},{"id":"14544","type":"Disease","text":["hypotension"],"offsets":[[1309,1320]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"14545","type":"Disease","text":["MR"],"offsets":[[1409,1411]],"normalized":[{"db_name":"MESH","db_id":"D008944"}]},{"id":"14546","type":"Disease","text":["MP"],"offsets":[[1413,1415]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"14547","type":"Chemical","text":["MZ"],"offsets":[[1443,1445]],"normalized":[{"db_name":"MESH","db_id":"D008874"}]},{"id":"14548","type":"Disease","text":["MP"],"offsets":[[1526,1528]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"14549","type":"Disease","text":["MR"],"offsets":[[1562,1564]],"normalized":[{"db_name":"MESH","db_id":"D008944"}]}],"events":[],"coreferences":[],"relations":[{"id":"14550","type":"CID","arg1_id":"14525","arg2_id":"14539","normalized":[]},{"id":"14551","type":"CID","arg1_id":"14525","arg2_id":"14540","normalized":[]},{"id":"14552","type":"CID","arg1_id":"14525","arg2_id":"14542","normalized":[]},{"id":"14553","type":"CID","arg1_id":"14526","arg2_id":"14539","normalized":[]},{"id":"14554","type":"CID","arg1_id":"14526","arg2_id":"14540","normalized":[]},{"id":"14555","type":"CID","arg1_id":"14526","arg2_id":"14542","normalized":[]},{"id":"14556","type":"CID","arg1_id":"14529","arg2_id":"14539","normalized":[]},{"id":"14557","type":"CID","arg1_id":"14529","arg2_id":"14540","normalized":[]},{"id":"14558","type":"CID","arg1_id":"14529","arg2_id":"14542","normalized":[]},{"id":"14559","type":"CID","arg1_id":"14530","arg2_id":"14539","normalized":[]},{"id":"14560","type":"CID","arg1_id":"14530","arg2_id":"14540","normalized":[]},{"id":"14561","type":"CID","arg1_id":"14530","arg2_id":"14542","normalized":[]},{"id":"14562","type":"CID","arg1_id":"14536","arg2_id":"14539","normalized":[]},{"id":"14563","type":"CID","arg1_id":"14536","arg2_id":"14540","normalized":[]},{"id":"14564","type":"CID","arg1_id":"14536","arg2_id":"14542","normalized":[]},{"id":"14565","type":"CID","arg1_id":"14537","arg2_id":"14539","normalized":[]},{"id":"14566","type":"CID","arg1_id":"14537","arg2_id":"14540","normalized":[]},{"id":"14567","type":"CID","arg1_id":"14537","arg2_id":"14542","normalized":[]},{"id":"14568","type":"CID","arg1_id":"14543","arg2_id":"14539","normalized":[]},{"id":"14569","type":"CID","arg1_id":"14543","arg2_id":"14540","normalized":[]},{"id":"14570","type":"CID","arg1_id":"14543","arg2_id":"14542","normalized":[]},{"id":"14571","type":"CID","arg1_id":"14547","arg2_id":"14539","normalized":[]},{"id":"14572","type":"CID","arg1_id":"14547","arg2_id":"14540","normalized":[]},{"id":"14573","type":"CID","arg1_id":"14547","arg2_id":"14542","normalized":[]}]}
{"id":"14574","document_id":"8231633","passages":[{"id":"14575","type":"title","text":["Effects of calcium channel blockers on bupivacaine-induced toxicity."],"offsets":[[0,68]]},{"id":"14576","type":"abstract","text":["The purpose of this study was to investigate the influence of calcium channel blockers on bupivacaine-induced acute toxicity. For each of the three tested calcium channel blockers (diltiazem, verapamil and bepridil) 6 groups of mice were treated by two different doses, i.e. 2 and 10 mg\/kg\/i.p., or an equal volume of saline for the control group (n = 20); 15 minutes later, all the animals were injected with a single 50 mg\/kg\/i.p. dose of bupivacaine. The convulsant activity, the time of latency to convulse and the mortality rate were assessed in each group. The local anesthetic-induced mortality was significantly increased by the three different calcium channel blockers. The convulsant activity of bupivacaine was not significantly modified but calcium channel blockers decreased the time of latency to obtain bupivacaine-induced convulsions; this effect was less pronounced with bepridil."],"offsets":[[69,966]]}],"entities":[{"id":"14577","type":"Chemical","text":["calcium"],"offsets":[[11,18]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"14578","type":"Chemical","text":["bupivacaine"],"offsets":[[39,50]],"normalized":[{"db_name":"MESH","db_id":"D002045"}]},{"id":"14579","type":"Disease","text":["toxicity"],"offsets":[[59,67]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"14580","type":"Chemical","text":["calcium"],"offsets":[[131,138]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"14581","type":"Chemical","text":["bupivacaine"],"offsets":[[159,170]],"normalized":[{"db_name":"MESH","db_id":"D002045"}]},{"id":"14582","type":"Disease","text":["toxicity"],"offsets":[[185,193]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"14583","type":"Chemical","text":["calcium"],"offsets":[[224,231]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"14584","type":"Chemical","text":["diltiazem"],"offsets":[[250,259]],"normalized":[{"db_name":"MESH","db_id":"D004110"}]},{"id":"14585","type":"Chemical","text":["verapamil"],"offsets":[[261,270]],"normalized":[{"db_name":"MESH","db_id":"D014700"}]},{"id":"14586","type":"Chemical","text":["bepridil"],"offsets":[[275,283]],"normalized":[{"db_name":"MESH","db_id":"D015764"}]},{"id":"14587","type":"Chemical","text":["bupivacaine"],"offsets":[[510,521]],"normalized":[{"db_name":"MESH","db_id":"D002045"}]},{"id":"14588","type":"Chemical","text":["calcium"],"offsets":[[722,729]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"14589","type":"Chemical","text":["bupivacaine"],"offsets":[[775,786]],"normalized":[{"db_name":"MESH","db_id":"D002045"}]},{"id":"14590","type":"Chemical","text":["calcium"],"offsets":[[822,829]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"14591","type":"Chemical","text":["bupivacaine"],"offsets":[[887,898]],"normalized":[{"db_name":"MESH","db_id":"D002045"}]},{"id":"14592","type":"Disease","text":["convulsions"],"offsets":[[907,918]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"14593","type":"Chemical","text":["bepridil"],"offsets":[[957,965]],"normalized":[{"db_name":"MESH","db_id":"D015764"}]}],"events":[],"coreferences":[],"relations":[{"id":"14594","type":"CID","arg1_id":"14578","arg2_id":"14592","normalized":[]},{"id":"14595","type":"CID","arg1_id":"14581","arg2_id":"14592","normalized":[]},{"id":"14596","type":"CID","arg1_id":"14587","arg2_id":"14592","normalized":[]},{"id":"14597","type":"CID","arg1_id":"14589","arg2_id":"14592","normalized":[]},{"id":"14598","type":"CID","arg1_id":"14591","arg2_id":"14592","normalized":[]}]}
{"id":"14599","document_id":"10091617","passages":[{"id":"14600","type":"title","text":["Selegiline-induced postural hypotension in Parkinson's disease: a longitudinal study on the effects of drug withdrawal."],"offsets":[[0,119]]},{"id":"14601","type":"abstract","text":["OBJECTIVES: The United Kingdom Parkinson's Disease Research Group (UKPDRG) trial found an increased mortality in patients with Parkinson's disease (PD) randomized to receive 10 mg selegiline per day and L-dopa compared with those taking L-dopa alone. Recently, we found that therapy with selegiline and L-dopa was associated with selective systolic orthostatic hypotension which was abolished by withdrawal of selegiline. This unwanted effect on postural blood pressure was not the result of underlying autonomic failure. The aims of this study were to confirm our previous findings in a separate cohort of patients and to determine the time course of the cardiovascular consequences of stopping selegiline in the expectation that this might shed light on the mechanisms by which the drug causes orthostatic hypotension. METHODS: The cardiovascular responses to standing and head-up tilt were studied repeatedly in PD patients receiving selegiline and as the drug was withdrawn. RESULTS: Head-up tilt caused systolic orthostatic hypotension which was marked in six of 20 PD patients on selegiline, one of whom lost consciousness with unrecordable blood pressures. A lesser degree of orthostatic hypotension occurred with standing. Orthostatic hypotension was ameliorated 4 days after withdrawal of selegiline and totally abolished 7 days after discontinuation of the drug. Stopping selegiline also significantly reduced the supine systolic and diastolic blood pressures consistent with a previously undescribed supine pressor action. CONCLUSION: This study confirms our previous finding that selegiline in combination with L-dopa is associated with selective orthostatic hypotension. The possibilities that these cardiovascular findings might be the result of non-selective inhibition of monoamine oxidase or of amphetamine and metamphetamine are discussed."],"offsets":[[120,1977]]}],"entities":[{"id":"14602","type":"Chemical","text":["Selegiline"],"offsets":[[0,10]],"normalized":[{"db_name":"MESH","db_id":"D012642"}]},{"id":"14603","type":"Disease","text":["postural hypotension"],"offsets":[[19,39]],"normalized":[{"db_name":"MESH","db_id":"D007024"}]},{"id":"14604","type":"Disease","text":["Parkinson's disease"],"offsets":[[43,62]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"14605","type":"Disease","text":["Parkinson's Disease"],"offsets":[[151,170]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"14606","type":"Disease","text":["Parkinson's disease"],"offsets":[[247,266]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"14607","type":"Disease","text":["PD"],"offsets":[[268,270]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"14608","type":"Chemical","text":["selegiline"],"offsets":[[300,310]],"normalized":[{"db_name":"MESH","db_id":"D012642"}]},{"id":"14609","type":"Chemical","text":["L-dopa"],"offsets":[[323,329]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"14610","type":"Chemical","text":["L-dopa"],"offsets":[[357,363]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"14611","type":"Chemical","text":["selegiline"],"offsets":[[408,418]],"normalized":[{"db_name":"MESH","db_id":"D012642"}]},{"id":"14612","type":"Chemical","text":["L-dopa"],"offsets":[[423,429]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"14613","type":"Disease","text":["systolic orthostatic hypotension"],"offsets":[[460,492]],"normalized":[{"db_name":"MESH","db_id":"D007024"}]},{"id":"14614","type":"Chemical","text":["selegiline"],"offsets":[[530,540]],"normalized":[{"db_name":"MESH","db_id":"D012642"}]},{"id":"14615","type":"Chemical","text":["selegiline"],"offsets":[[816,826]],"normalized":[{"db_name":"MESH","db_id":"D012642"}]},{"id":"14616","type":"Disease","text":["orthostatic hypotension"],"offsets":[[916,939]],"normalized":[{"db_name":"MESH","db_id":"D007024"}]},{"id":"14617","type":"Disease","text":["PD"],"offsets":[[1035,1037]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"14618","type":"Chemical","text":["selegiline"],"offsets":[[1057,1067]],"normalized":[{"db_name":"MESH","db_id":"D012642"}]},{"id":"14619","type":"Disease","text":["systolic orthostatic hypotension"],"offsets":[[1128,1160]],"normalized":[{"db_name":"MESH","db_id":"D007024"}]},{"id":"14620","type":"Disease","text":["PD"],"offsets":[[1191,1193]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"14621","type":"Chemical","text":["selegiline"],"offsets":[[1206,1216]],"normalized":[{"db_name":"MESH","db_id":"D012642"}]},{"id":"14622","type":"Disease","text":["orthostatic hypotension"],"offsets":[[1303,1326]],"normalized":[{"db_name":"MESH","db_id":"D007024"}]},{"id":"14623","type":"Disease","text":["Orthostatic hypotension"],"offsets":[[1351,1374]],"normalized":[{"db_name":"MESH","db_id":"D007024"}]},{"id":"14624","type":"Chemical","text":["selegiline"],"offsets":[[1418,1428]],"normalized":[{"db_name":"MESH","db_id":"D012642"}]},{"id":"14625","type":"Chemical","text":["selegiline"],"offsets":[[1502,1512]],"normalized":[{"db_name":"MESH","db_id":"D012642"}]},{"id":"14626","type":"Disease","text":["reduced the supine systolic and diastolic blood pressures"],"offsets":[[1532,1589]],"normalized":[{"db_name":"MESH","db_id":"D007024"}]},{"id":"14627","type":"Chemical","text":["selegiline"],"offsets":[[1712,1722]],"normalized":[{"db_name":"MESH","db_id":"D012642"}]},{"id":"14628","type":"Chemical","text":["L-dopa"],"offsets":[[1743,1749]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"14629","type":"Disease","text":["orthostatic 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{"id":"14712","document_id":"19269743","passages":[{"id":"14713","type":"title","text":["Explicit episodic memory for sensory-discriminative components of capsaicin-induced pain: immediate and delayed ratings."],"offsets":[[0,120]]},{"id":"14714","type":"abstract","text":["Pain memory is thought to affect future pain sensitivity and thus contribute to clinical pain conditions. Systematic investigations of the human capacity to remember sensory features of experimental pain are sparse. In order to address long-term pain memory, nine healthy male volunteers received intradermal injections of three doses of capsaicin (0.05, 1 and 20 microg, separated by 15 min breaks), each given three times in a balanced design across three sessions at one week intervals. Pain rating was performed using a computerized visual analogue scale (0-100) digitized at 1\/s, either immediately online or one hour or one day after injection. Subjects also recalled their pains one week later. Capsaicin injection reliably induced a dose-dependent flare (p<0.001) without any difference within or across sessions. The strong burning pain decayed exponentially within a few minutes. Subjects were able to reliably discriminate pain magnitude and duration across capsaicin doses (both p<0.001), regardless of whether first-time ratings were requested immediately, after one hour or after one day. Pain recall after one week was similarly precise (magnitude: p<0.01, duration: p<0.05). Correlation with rating recall after one week was best when first-time ratings were requested as late as one day after injection (R(2)=0.79) indicating that both rating retrievals utilized similar memory traces. These results indicate a reliable memory for magnitude and duration of experimentally induced pain. The data further suggest that the consolidation of this memory is an important interim stage, and may take up to one day."],"offsets":[[121,1745]]}],"entities":[{"id":"14715","type":"Chemical","text":["capsaicin"],"offsets":[[66,75]],"normalized":[{"db_name":"MESH","db_id":"D002211"}]},{"id":"14716","type":"Disease","text":["pain"],"offsets":[[84,88]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"14717","type":"Disease","text":["Pain"],"offsets":[[121,125]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"14718","type":"Disease","text":["pain"],"offsets":[[161,165]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"14719","type":"Disease","text":["pain"],"offsets":[[210,214]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"14720","type":"Disease","text":["pain"],"offsets":[[320,324]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"14721","type":"Disease","text":["pain"],"offsets":[[367,371]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"14722","type":"Chemical","text":["capsaicin"],"offsets":[[459,468]],"normalized":[{"db_name":"MESH","db_id":"D002211"}]},{"id":"14723","type":"Disease","text":["Pain"],"offsets":[[611,615]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"14724","type":"Disease","text":["pains"],"offsets":[[801,806]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"14725","type":"Chemical","text":["Capsaicin"],"offsets":[[823,832]],"normalized":[{"db_name":"MESH","db_id":"D002211"}]},{"id":"14726","type":"Disease","text":["pain"],"offsets":[[962,966]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"14727","type":"Disease","text":["pain"],"offsets":[[1055,1059]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"14728","type":"Chemical","text":["capsaicin"],"offsets":[[1090,1099]],"normalized":[{"db_name":"MESH","db_id":"D002211"}]},{"id":"14729","type":"Disease","text":["Pain"],"offsets":[[1224,1228]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"14730","type":"Disease","text":["pain"],"offsets":[[1618,1622]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]}],"events":[],"coreferences":[],"relations":[{"id":"14731","type":"CID","arg1_id":"14715","arg2_id":"14716","normalized":[]},{"id":"14732","type":"CID","arg1_id":"14715","arg2_id":"14717","normalized":[]},{"id":"14733","type":"CID","arg1_id":"14715","arg2_id":"14718","normalized":[]},{"id":"14734","type":"CID","arg1_id":"14715","arg2_id":"14719","normalized":[]},{"id":"14735","type":"CID","arg1_id":"14715","arg2_id":"14720","normalized":[]},{"id":"14736","type":"CID","arg1_id":"14715","arg2_id":"14721","normalized":[]},{"id":"14737","type":"CID","arg1_id":"14715","arg2_id":"14723","normalized":[]},{"id":"14738","type":"CID","arg1_id":"14715","arg2_id":"14724","normalized":[]},{"id":"14739","type":"CID","arg1_id":"14715","arg2_id":"14726","normalized":[]},{"id":"14740","type":"CID","arg1_id":"14715","arg2_id":"14727","normalized":[]},{"id":"14741","type":"CID","arg1_id":"14715","arg2_id":"14729","normalized":[]},{"id":"14742","type":"CID","arg1_id":"14715","arg2_id":"14730","normalized":[]},{"id":"14743","type":"CID","arg1_id":"14722","arg2_id":"14716","normalized":[]},{"id":"14744","type":"CID","arg1_id":"14722","arg2_id":"14717","normalized":[]},{"id":"14745","type":"CID","arg1_id":"14722","arg2_id":"14718","normalized":[]},{"id":"14746","type":"CID","arg1_id":"14722","arg2_id":"14719","normalized":[]},{"id":"14747","type":"CID","arg1_id":"14722","arg2_id":"14720","normalized":[]},{"id":"14748","type":"CID","arg1_id":"14722","arg2_id":"14721","normalized":[]},{"id":"14749","type":"CID","arg1_id":"14722","arg2_id":"14723","normalized":[]},{"id":"14750","type":"CID","arg1_id":"14722","arg2_id":"14724","normalized":[]},{"id":"14751","type":"CID","arg1_id":"14722","arg2_id":"14726","normalized":[]},{"id":"14752","type":"CID","arg1_id":"14722","arg2_id":"14727","normalized":[]},{"id":"14753","type":"CID","arg1_id":"14722","arg2_id":"14729","normalized":[]},{"id":"14754","type":"CID","arg1_id":"14722","arg2_id":"14730","normalized":[]},{"id":"14755","type":"CID","arg1_id":"14725","arg2_id":"14716","normalized":[]},{"id":"14756","type":"CID","arg1_id":"14725","arg2_id":"14717","normalized":[]},{"id":"14757","type":"CID","arg1_id":"14725","arg2_id":"14718","normalized":[]},{"id":"14758","type":"CID","arg1_id":"14725","arg2_id":"14719","normalized":[]},{"id":"14759","type":"CID","arg1_id":"14725","arg2_id":"14720","normalized":[]},{"id":"14760","type":"CID","arg1_id":"14725","arg2_id":"14721","normalized":[]},{"id":"14761","type":"CID","arg1_id":"14725","arg2_id":"14723","normalized":[]},{"id":"14762","type":"CID","arg1_id":"14725","arg2_id":"14724","normalized":[]},{"id":"14763","type":"CID","arg1_id":"14725","arg2_id":"14726","normalized":[]},{"id":"14764","type":"CID","arg1_id":"14725","arg2_id":"14727","normalized":[]},{"id":"14765","type":"CID","arg1_id":"14725","arg2_id":"14729","normalized":[]},{"id":"14766","type":"CID","arg1_id":"14725","arg2_id":"14730","normalized":[]},{"id":"14767","type":"CID","arg1_id":"14728","arg2_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{"id":"14779","document_id":"3070035","passages":[{"id":"14780","type":"title","text":["Reversibility of captopril-induced renal insufficiency after prolonged use in an unusual case of renovascular hypertension."],"offsets":[[0,123]]},{"id":"14781","type":"abstract","text":["We report a case of severe hypertension with an occluded renal artery to a solitary kidney, who developed sudden deterioration of renal function following treatment with captopril. His renal function remained impaired but stable during 2 years' treatment with captopril but returned to pre-treatment levels soon after cessation of the drug. This indicates reversibility in captopril-induced renal failure even after its prolonged use and suggests that no organic damage occurs to glomerular arterioles following chronic ACE inhibition."],"offsets":[[124,659]]}],"entities":[{"id":"14782","type":"Chemical","text":["captopril"],"offsets":[[17,26]],"normalized":[{"db_name":"MESH","db_id":"D002216"}]},{"id":"14783","type":"Disease","text":["renal insufficiency"],"offsets":[[35,54]],"normalized":[{"db_name":"MESH","db_id":"D051437"}]},{"id":"14784","type":"Disease","text":["renovascular hypertension"],"offsets":[[97,122]],"normalized":[{"db_name":"MESH","db_id":"D006978"}]},{"id":"14785","type":"Disease","text":["hypertension"],"offsets":[[151,163]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"14786","type":"Disease","text":["sudden deterioration of renal function"],"offsets":[[230,268]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"14787","type":"Chemical","text":["captopril"],"offsets":[[294,303]],"normalized":[{"db_name":"MESH","db_id":"D002216"}]},{"id":"14788","type":"Chemical","text":["captopril"],"offsets":[[384,393]],"normalized":[{"db_name":"MESH","db_id":"D002216"}]},{"id":"14789","type":"Chemical","text":["captopril"],"offsets":[[497,506]],"normalized":[{"db_name":"MESH","db_id":"D002216"}]},{"id":"14790","type":"Disease","text":["renal failure"],"offsets":[[515,528]],"normalized":[{"db_name":"MESH","db_id":"D051437"}]}],"events":[],"coreferences":[],"relations":[{"id":"14791","type":"CID","arg1_id":"14782","arg2_id":"14786","normalized":[]},{"id":"14792","type":"CID","arg1_id":"14787","arg2_id":"14786","normalized":[]},{"id":"14793","type":"CID","arg1_id":"14788","arg2_id":"14786","normalized":[]},{"id":"14794","type":"CID","arg1_id":"14789","arg2_id":"14786","normalized":[]}]}
{"id":"14795","document_id":"1147734","passages":[{"id":"14796","type":"title","text":["Liver disease caused by propylthiouracil."],"offsets":[[0,41]]},{"id":"14797","type":"abstract","text":["This report presents the clinical, laboratory, and light and electron microscopic observations on a patient with chronic active (aggressive) hepatitis caused by the administration of propylthiouracil. This is an addition to the list of drugs that must be considered in the evaluation of chronic liver disease."],"offsets":[[42,351]]}],"entities":[{"id":"14798","type":"Disease","text":["Liver disease"],"offsets":[[0,13]],"normalized":[{"db_name":"MESH","db_id":"D008107"}]},{"id":"14799","type":"Chemical","text":["propylthiouracil"],"offsets":[[24,40]],"normalized":[{"db_name":"MESH","db_id":"D011441"}]},{"id":"14800","type":"Disease","text":["chronic active (aggressive) hepatitis"],"offsets":[[155,192]],"normalized":[{"db_name":"MESH","db_id":"D006521"}]},{"id":"14801","type":"Chemical","text":["propylthiouracil"],"offsets":[[225,241]],"normalized":[{"db_name":"MESH","db_id":"D011441"}]},{"id":"14802","type":"Disease","text":["liver disease"],"offsets":[[337,350]],"normalized":[{"db_name":"MESH","db_id":"D008107"}]}],"events":[],"coreferences":[],"relations":[{"id":"14803","type":"CID","arg1_id":"14799","arg2_id":"14800","normalized":[]},{"id":"14804","type":"CID","arg1_id":"14801","arg2_id":"14800","normalized":[]}]}
{"id":"14805","document_id":"12202650","passages":[{"id":"14806","type":"title","text":["Capsaicin-induced muscle pain alters the excitability of the human jaw-stretch reflex."],"offsets":[[0,86]]},{"id":"14807","type":"abstract","text":["The pathophysiology of painful temporomandibular disorders is not fully understood, but evidence suggests that muscle pain modulates motor function in characteristic ways. This study tested the hypothesis that activation of nociceptive muscle afferent fibers would be linked to an increased excitability of the human jaw-stretch reflex and whether this process would be sensitive to length and velocity of the stretch. Capsaicin (10 micro g) was injected into the masseter muscle to induce pain in 11 healthy volunteers. Short-latency reflex responses were evoked in the masseter and temporalis muscles by a stretch device with different velocities and displacements before, during, and after the pain. The normalized reflex amplitude increased with an increase in velocity at a given displacement, but remained constant with different displacements at a given velocity. The normalized reflex amplitude was significantly higher during pain, but only at faster stretches in the painful muscle. Increased sensitivity of the fusimotor system during acute muscle pain could be one likely mechanism to explain the findings."],"offsets":[[87,1205]]}],"entities":[{"id":"14808","type":"Chemical","text":["Capsaicin"],"offsets":[[0,9]],"normalized":[{"db_name":"MESH","db_id":"D002211"}]},{"id":"14809","type":"Disease","text":["muscle pain"],"offsets":[[18,29]],"normalized":[{"db_name":"MESH","db_id":"D063806"}]},{"id":"14810","type":"Disease","text":["temporomandibular disorders"],"offsets":[[118,145]],"normalized":[{"db_name":"MESH","db_id":"D013705"}]},{"id":"14811","type":"Disease","text":["muscle pain"],"offsets":[[198,209]],"normalized":[{"db_name":"MESH","db_id":"D063806"}]},{"id":"14812","type":"Disease","text":["nociceptive muscle"],"offsets":[[311,329]],"normalized":[{"db_name":"MESH","db_id":"D063806"}]},{"id":"14813","type":"Chemical","text":["Capsaicin"],"offsets":[[506,515]],"normalized":[{"db_name":"MESH","db_id":"D002211"}]},{"id":"14814","type":"Disease","text":["pain"],"offsets":[[577,581]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"14815","type":"Disease","text":["pain"],"offsets":[[784,788]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"14816","type":"Disease","text":["pain"],"offsets":[[1022,1026]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"14817","type":"Disease","text":["painful muscle"],"offsets":[[1064,1078]],"normalized":[{"db_name":"MESH","db_id":"D063806"}]},{"id":"14818","type":"Disease","text":["muscle pain"],"offsets":[[1139,1150]],"normalized":[{"db_name":"MESH","db_id":"D063806"}]}],"events":[],"coreferences":[],"relations":[{"id":"14819","type":"CID","arg1_id":"14808","arg2_id":"14814","normalized":[]},{"id":"14820","type":"CID","arg1_id":"14808","arg2_id":"14815","normalized":[]},{"id":"14821","type":"CID","arg1_id":"14808","arg2_id":"14816","normalized":[]},{"id":"14822","type":"CID","arg1_id":"14813","arg2_id":"14814","normalized":[]},{"id":"14823","type":"CID","arg1_id":"14813","arg2_id":"14815","normalized":[]},{"id":"14824","type":"CID","arg1_id":"14813","arg2_id":"14816","normalized":[]}]}
{"id":"14825","document_id":"18951540","passages":[{"id":"14826","type":"title","text":["Repetitive transcranial magnetic stimulation for levodopa-induced dyskinesias in Parkinson's disease."],"offsets":[[0,101]]},{"id":"14827","type":"abstract","text":["In a placebo-controlled, single-blinded, crossover study, we assessed the effect of \"real\" repetitive transcranial magnetic stimulation (rTMS) versus \"sham\" rTMS (placebo) on peak dose dyskinesias in patients with Parkinson's disease (PD). Ten patients with PD and prominent dyskinesias had rTMS (1,800 pulses; 1 Hz rate) delivered over the motor cortex for 4 consecutive days twice, once real stimuli and once sham stimulation were used; evaluations were done at the baseline and 1 day after the end of each of the treatment series. Direct comparison between sham and real rTMS effects showed no significant difference in clinician-assessed dyskinesia severity. However, comparison with the baseline showed small but significant reduction in dyskinesia severity following real rTMS but not placebo. The major effect was on dystonia subscore. Similarly, in patient diaries, although both treatments caused reduction in subjective dyskinesia scores during the days of intervention, the effect was sustained for 3 days after the intervention for the real rTMS only. Following rTMS, no side effects and no adverse effects on motor function and PD symptoms were noted. The results suggest the existence of residual beneficial clinical aftereffects of consecutive daily applications of low-frequency rTMS on dyskinesias in PD. The effects may be further exploited for potential therapeutic uses."],"offsets":[[102,1492]]}],"entities":[{"id":"14828","type":"Chemical","text":["levodopa"],"offsets":[[49,57]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"14829","type":"Disease","text":["dyskinesias"],"offsets":[[66,77]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"14830","type":"Disease","text":["Parkinson's disease"],"offsets":[[81,100]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"14831","type":"Disease","text":["dyskinesias"],"offsets":[[287,298]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"14832","type":"Disease","text":["Parkinson's disease"],"offsets":[[316,335]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"14833","type":"Disease","text":["PD"],"offsets":[[337,339]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"14834","type":"Disease","text":["PD"],"offsets":[[360,362]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"14835","type":"Disease","text":["dyskinesias"],"offsets":[[377,388]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"14836","type":"Disease","text":["dyskinesia"],"offsets":[[744,754]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"14837","type":"Disease","text":["dyskinesia"],"offsets":[[845,855]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"14838","type":"Disease","text":["dystonia"],"offsets":[[926,934]],"normalized":[{"db_name":"MESH","db_id":"D004421"}]},{"id":"14839","type":"Disease","text":["dyskinesia"],"offsets":[[1032,1042]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"14840","type":"Disease","text":["PD"],"offsets":[[1243,1245]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"14841","type":"Disease","text":["dyskinesias"],"offsets":[[1405,1416]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"14842","type":"Disease","text":["PD"],"offsets":[[1420,1422]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]}],"events":[],"coreferences":[],"relations":[{"id":"14843","type":"CID","arg1_id":"14828","arg2_id":"14829","normalized":[]},{"id":"14844","type":"CID","arg1_id":"14828","arg2_id":"14831","normalized":[]},{"id":"14845","type":"CID","arg1_id":"14828","arg2_id":"14835","normalized":[]},{"id":"14846","type":"CID","arg1_id":"14828","arg2_id":"14836","normalized":[]},{"id":"14847","type":"CID","arg1_id":"14828","arg2_id":"14837","normalized":[]},{"id":"14848","type":"CID","arg1_id":"14828","arg2_id":"14839","normalized":[]},{"id":"14849","type":"CID","arg1_id":"14828","arg2_id":"14841","normalized":[]}]}
{"id":"14850","document_id":"19657887","passages":[{"id":"14851","type":"title","text":["Disulfiram-like syndrome after hydrogen cyanamide professional skin exposure: two case reports in France."],"offsets":[[0,105]]},{"id":"14852","type":"abstract","text":["Hydrogen cyanamide is a plant growth regulator used in agriculture to induce bud break in fruit trees. Contact with the skin can result in percutaneous absorption of the substance that inhibits aldehyde dehydrogenase and can induce acetaldehyde syndrome in case of alcohol use. The purpose of this report is to describe two cases of a disulfiram-like syndrome following occupational exposure to hydrogen cyanamide. The first case involved a 59-year-old man who used Dormex, which contains hydrogen cyanamide, without protection after consuming a large amount of alcohol during a meal. In less than 1 hour after the ingestion of alcohol, he developed malaise with flushing of the face, tachycardia, and dyspnea. Manifestations regressed spontaneously under surveillance in the hospital. The second case occurred in a 55-year-old farmer following cutaneous contact with Dormex. Five hours after exposure, he developed disulfiram-like syndrome with flushing, tachycardia, and arterial hypotension after consuming three glasses of wine. The patient recovered spontaneously in 3 hours under surveillance in the hospital. These cases confirm the necessity of avoiding alcohol consumption as recommended in the instructions for use of Dormex and of preventing cutaneous contact during use."],"offsets":[[106,1388]]}],"entities":[{"id":"14853","type":"Chemical","text":["Disulfiram"],"offsets":[[0,10]],"normalized":[{"db_name":"MESH","db_id":"D004221"}]},{"id":"14854","type":"Chemical","text":["hydrogen cyanamide"],"offsets":[[31,49]],"normalized":[{"db_name":"MESH","db_id":"D003484"}]},{"id":"14855","type":"Chemical","text":["Hydrogen cyanamide"],"offsets":[[106,124]],"normalized":[{"db_name":"MESH","db_id":"D003484"}]},{"id":"14856","type":"Chemical","text":["aldehyde"],"offsets":[[300,308]],"normalized":[{"db_name":"MESH","db_id":"D000079"}]},{"id":"14857","type":"Chemical","text":["acetaldehyde"],"offsets":[[338,350]],"normalized":[{"db_name":"MESH","db_id":"D000079"}]},{"id":"14858","type":"Chemical","text":["alcohol"],"offsets":[[371,378]],"normalized":[{"db_name":"MESH","db_id":"D000431"}]},{"id":"14859","type":"Chemical","text":["disulfiram"],"offsets":[[441,451]],"normalized":[{"db_name":"MESH","db_id":"D004221"}]},{"id":"14860","type":"Chemical","text":["hydrogen cyanamide"],"offsets":[[501,519]],"normalized":[{"db_name":"MESH","db_id":"D003484"}]},{"id":"14861","type":"Chemical","text":["Dormex"],"offsets":[[572,578]],"normalized":[{"db_name":"MESH","db_id":"D003484"}]},{"id":"14862","type":"Chemical","text":["hydrogen cyanamide"],"offsets":[[595,613]],"normalized":[{"db_name":"MESH","db_id":"D003484"}]},{"id":"14863","type":"Chemical","text":["alcohol"],"offsets":[[668,675]],"normalized":[{"db_name":"MESH","db_id":"D000431"}]},{"id":"14864","type":"Chemical","text":["alcohol"],"offsets":[[734,741]],"normalized":[{"db_name":"MESH","db_id":"D000431"}]},{"id":"14865","type":"Disease","text":["flushing of the face"],"offsets":[[769,789]],"normalized":[{"db_name":"MESH","db_id":"D005483"}]},{"id":"14866","type":"Disease","text":["tachycardia"],"offsets":[[791,802]],"normalized":[{"db_name":"MESH","db_id":"D013610"}]},{"id":"14867","type":"Disease","text":["dyspnea"],"offsets":[[808,815]],"normalized":[{"db_name":"MESH","db_id":"D004417"}]},{"id":"14868","type":"Chemical","text":["Dormex"],"offsets":[[974,980]],"normalized":[{"db_name":"MESH","db_id":"D003484"}]},{"id":"14869","type":"Chemical","text":["disulfiram"],"offsets":[[1022,1032]],"normalized":[{"db_name":"MESH","db_id":"D004221"}]},{"id":"14870","type":"Disease","text":["flushing"],"offsets":[[1052,1060]],"normalized":[{"db_name":"MESH","db_id":"D005483"}]},{"id":"14871","type":"Disease","text":["tachycardia"],"offsets":[[1062,1073]],"normalized":[{"db_name":"MESH","db_id":"D013610"}]},{"id":"14872","type":"Disease","text":["arterial hypotension"],"offsets":[[1079,1099]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"14873","type":"Chemical","text":["alcohol"],"offsets":[[1268,1275]],"normalized":[{"db_name":"MESH","db_id":"D000431"}]},{"id":"14874","type":"Chemical","text":["Dormex"],"offsets":[[1334,1340]],"normalized":[{"db_name":"MESH","db_id":"D003484"}]}],"events":[],"coreferences":[],"relations":[{"id":"14875","type":"CID","arg1_id":"14858","arg2_id":"14872","normalized":[]},{"id":"14876","type":"CID","arg1_id":"14863","arg2_id":"14872","normalized":[]},{"id":"14877","type":"CID","arg1_id":"14864","arg2_id":"14872","normalized":[]},{"id":"14878","type":"CID","arg1_id":"14873","arg2_id":"14872","normalized":[]},{"id":"14879","type":"CID","arg1_id":"14858","arg2_id":"14865","normalized":[]},{"id":"14880","type":"CID","arg1_id":"14858","arg2_id":"14870","normalized":[]},{"id":"14881","type":"CID","arg1_id":"14863","arg2_id":"14865","normalized":[]},{"id":"14882","type":"CID","arg1_id":"14863","arg2_id":"14870","normalized":[]},{"id":"14883","type":"CID","arg1_id":"14864","arg2_id":"14865","normalized":[]},{"id":"14884","type":"CID","arg1_id":"14864","arg2_id":"14870","normalized":[]},{"id":"14885","type":"CID","arg1_id":"14873","arg2_id":"14865","normalized":[]},{"id":"14886","type":"CID","arg1_id":"14873","arg2_id":"14870","normalized":[]},{"id":"14887","type":"CID","arg1_id":"14854","arg2_id":"14872","normalized":[]},{"id":"14888","type":"CID","arg1_id":"14855","arg2_id":"14872","normalized":[]},{"id":"14889","type":"CID","arg1_id":"14860","arg2_id":"14872","normalized":[]},{"id":"14890","type":"CID","arg1_id":"14861","arg2_id":"14872","normalized":[]},{"id":"14891","type":"CID","arg1_id":"14862","arg2_id":"14872","normalized":[]},{"id":"14892","type":"CID","arg1_id":"14868","arg2_id":"14872","normalized":[]},{"id":"14893","type":"CID","arg1_id":"14874","arg2_id":"14872","normalized":[]},{"id":"14894","type":"CID","arg1_id":"14858","arg2_id":"14867","normalized":[]},{"id":"14895","type":"CID","arg1_id":"14863","arg2_id":"14867","normalized":[]},{"id":"14896","type":"CID","arg1_id":"14864","arg2_id":"14867","normalized":[]},{"id":"14897","type":"CID","arg1_id":"14873","arg2_id":"14867","normalized":[]},{"id":"14898","type":"CID","arg1_id":"14854","arg2_id":"14866","normalized":[]},{"id":"14899","type":"CID","arg1_id":"14854","arg2_id":"14871","normalized":[]},{"id":"14900","type":"CID","arg1_id":"14855","arg2_id":"14866","normalized":[]},{"id":"14901","type":"CID","arg1_id":"14855","arg2_id":"14871","normalized":[]},{"id":"14902","type":"CID","arg1_id":"14860","arg2_id":"14866","normalized":[]},{"id":"14903","type":"CID","arg1_id":"14860","arg2_id":"14871","normalized":[]},{"id":"14904","type":"CID","arg1_id":"14861","arg2_id":"14866","normalized":[]},{"id":"14905","type":"CID","arg1_id":"14861","arg2_id":"14871","normalized":[]},{"id":"14906","type":"CID","arg1_id":"14862","arg2_id":"14866","normalized":[]},{"id":"14907","type":"CID","arg1_id":"14862","arg2_id":"14871","normalized":[]},{"id":"14908","type":"CID","arg1_id":"14868","arg2_id":"14866","normalized":[]},{"id":"14909","type":"CID","arg1_id":"14868","arg2_id":"14871","normalized":[]},{"id":"14910","type":"CID","arg1_id":"14874","arg2_id":"14866","normalized":[]},{"id":"14911","type":"CID","arg1_id":"14874","arg2_id":"14871","normalized":[]},{"id":"14912","type":"CID","arg1_id":"14854","arg2_id":"14867","normalized":[]},{"id":"14913","type":"CID","arg1_id":"14855","arg2_id":"14867","normalized":[]},{"id":"14914","type":"CID","arg1_id":"14860","arg2_id":"14867","normalized":[]},{"id":"14915","type":"CID","arg1_id":"14861","arg2_id":"14867","normalized":[]},{"id":"14916","type":"CID","arg1_id":"14862","arg2_id":"14867","normalized":[]},{"id":"14917","type":"CID","arg1_id":"14868","arg2_id":"14867","normalized":[]},{"id":"14918","type":"CID","arg1_id":"14874","arg2_id":"14867","normalized":[]},{"id":"14919","type":"CID","arg1_id":"14858","arg2_id":"14866","normalized":[]},{"id":"14920","type":"CID","arg1_id":"14858","arg2_id":"14871","normalized":[]},{"id":"14921","type":"CID","arg1_id":"14863","arg2_id":"14866","normalized":[]},{"id":"14922","type":"CID","arg1_id":"14863","arg2_id":"14871","normalized":[]},{"id":"14923","type":"CID","arg1_id":"14864","arg2_id":"14866","normalized":[]},{"id":"14924","type":"CID","arg1_id":"14864","arg2_id":"14871","normalized":[]},{"id":"14925","type":"CID","arg1_id":"14873","arg2_id":"14866","normalized":[]},{"id":"14926","type":"CID","arg1_id":"14873","arg2_id":"14871","normalized":[]},{"id":"14927","type":"CID","arg1_id":"14854","arg2_id":"14865","normalized":[]},{"id":"14928","type":"CID","arg1_id":"14854","arg2_id":"14870","normalized":[]},{"id":"14929","type":"CID","arg1_id":"14855","arg2_id":"14865","normalized":[]},{"id":"14930","type":"CID","arg1_id":"14855","arg2_id":"14870","normalized":[]},{"id":"14931","type":"CID","arg1_id":"14860","arg2_id":"14865","normalized":[]},{"id":"14932","type":"CID","arg1_id":"14860","arg2_id":"14870","normalized":[]},{"id":"14933","type":"CID","arg1_id":"14861","arg2_id":"14865","normalized":[]},{"id":"14934","type":"CID","arg1_id":"14861","arg2_id":"14870","normalized":[]},{"id":"14935","type":"CID","arg1_id":"14862","arg2_id":"14865","normalized":[]},{"id":"14936","type":"CID","arg1_id":"14862","arg2_id":"14870","normalized":[]},{"id":"14937","type":"CID","arg1_id":"14868","arg2_id":"14865","normalized":[]},{"id":"14938","type":"CID","arg1_id":"14868","arg2_id":"14870","normalized":[]},{"id":"14939","type":"CID","arg1_id":"14874","arg2_id":"14865","normalized":[]},{"id":"14940","type":"CID","arg1_id":"14874","arg2_id":"14870","normalized":[]}]}
{"id":"14941","document_id":"9660111","passages":[{"id":"14942","type":"title","text":["Repeated trimipramine induces dopamine D2\/D3 and alpha1-adrenergic up-regulation."],"offsets":[[0,81]]},{"id":"14943","type":"abstract","text":["Trimipramine (TRI), which shows a clinical antidepressant activity, is chemically related to imipramine but does not inhibit the reuptake of noradrenaline and 5-hydroxytryptamine, nor does it induce beta-adrenergic down-regulation. The mechanism of its antidepressant activity is still unknown. The aim of the present study was to find out whether TRI given repeatedly was able to induce adaptive changes in the dopaminergic and alpha1-adrenergic systems, demonstrated by us previously for various antidepressants. TRI was given to male Wistar rats and male Albino Swiss mice perorally twice daily for 14 days. In the acute experiment TRI (given i.p.) does not antagonize the reserpine hypothermia in mice and does not potentiate the 5-hydroxytryptophan head twitches in rats. TRI given repeatedly to rats increases the locomotor hyperactivity induced by d-amphetamine, quinpirole and (+)-7-hydroxy-dipropyloaminotetralin (dopamine D2 and D3 effects). The stereotypies induced by d-amphetamine or apomorphine are not potentiated by TRI. It increases the behaviour stimulation evoked by phenylephrine (given intraventricularly) in rats, evaluated in the open field test as well as the aggressiveness evoked by clonidine in mice, both these effects being mediated by an alpha1-adrenergic receptor. It may be concluded that, like other tricyclic antidepressants studied previously, TRI given repeatedly increases the responsiveness of brain dopamine D2 and D3 (locomotor activity but not stereotypy) as well as alpha1-adrenergic receptors to their agonists. A question arises whether the reuptake inhibition is of any importance to the adaptive changes induced by repeated antidepressants, suggested to be responsible for the antidepressant activity."],"offsets":[[82,1829]]}],"entities":[{"id":"14944","type":"Chemical","text":["trimipramine"],"offsets":[[9,21]],"normalized":[{"db_name":"MESH","db_id":"D014299"}]},{"id":"14945","type":"Chemical","text":["dopamine"],"offsets":[[30,38]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"14946","type":"Chemical","text":["Trimipramine"],"offsets":[[82,94]],"normalized":[{"db_name":"MESH","db_id":"D014299"}]},{"id":"14947","type":"Chemical","text":["TRI"],"offsets":[[96,99]],"normalized":[{"db_name":"MESH","db_id":"D014299"}]},{"id":"14948","type":"Chemical","text":["antidepressant"],"offsets":[[125,139]],"normalized":[{"db_name":"MESH","db_id":"D000928"}]},{"id":"14949","type":"Chemical","text":["imipramine"],"offsets":[[175,185]],"normalized":[{"db_name":"MESH","db_id":"D007099"}]},{"id":"14950","type":"Chemical","text":["noradrenaline"],"offsets":[[223,236]],"normalized":[{"db_name":"MESH","db_id":"D009638"}]},{"id":"14951","type":"Chemical","text":["5-hydroxytryptamine"],"offsets":[[241,260]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"14952","type":"Chemical","text":["antidepressant"],"offsets":[[335,349]],"normalized":[{"db_name":"MESH","db_id":"D000928"}]},{"id":"14953","type":"Chemical","text":["TRI"],"offsets":[[430,433]],"normalized":[{"db_name":"MESH","db_id":"D014299"}]},{"id":"14954","type":"Chemical","text":["antidepressants"],"offsets":[[580,595]],"normalized":[{"db_name":"MESH","db_id":"D000928"}]},{"id":"14955","type":"Chemical","text":["TRI"],"offsets":[[597,600]],"normalized":[{"db_name":"MESH","db_id":"D014299"}]},{"id":"14956","type":"Chemical","text":["TRI"],"offsets":[[717,720]],"normalized":[{"db_name":"MESH","db_id":"D014299"}]},{"id":"14957","type":"Chemical","text":["reserpine"],"offsets":[[758,767]],"normalized":[{"db_name":"MESH","db_id":"D012110"}]},{"id":"14958","type":"Disease","text":["hypothermia"],"offsets":[[768,779]],"normalized":[{"db_name":"MESH","db_id":"D007035"}]},{"id":"14959","type":"Chemical","text":["5-hydroxytryptophan"],"offsets":[[816,835]],"normalized":[{"db_name":"MESH","db_id":"D006916"}]},{"id":"14960","type":"Chemical","text":["TRI"],"offsets":[[859,862]],"normalized":[{"db_name":"MESH","db_id":"D014299"}]},{"id":"14961","type":"Disease","text":["hyperactivity"],"offsets":[[912,925]],"normalized":[{"db_name":"MESH","db_id":"D006948"}]},{"id":"14962","type":"Chemical","text":["d-amphetamine"],"offsets":[[937,950]],"normalized":[{"db_name":"MESH","db_id":"D003913"}]},{"id":"14963","type":"Chemical","text":["quinpirole"],"offsets":[[952,962]],"normalized":[{"db_name":"MESH","db_id":"D019257"}]},{"id":"14964","type":"Chemical","text":["dopamine"],"offsets":[[1005,1013]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"14965","type":"Chemical","text":["d-amphetamine"],"offsets":[[1062,1075]],"normalized":[{"db_name":"MESH","db_id":"D003913"}]},{"id":"14966","type":"Chemical","text":["apomorphine"],"offsets":[[1079,1090]],"normalized":[{"db_name":"MESH","db_id":"D001058"}]},{"id":"14967","type":"Chemical","text":["TRI"],"offsets":[[1114,1117]],"normalized":[{"db_name":"MESH","db_id":"D014299"}]},{"id":"14968","type":"Chemical","text":["phenylephrine"],"offsets":[[1168,1181]],"normalized":[{"db_name":"MESH","db_id":"D010656"}]},{"id":"14969","type":"Disease","text":["aggressiveness"],"offsets":[[1266,1280]],"normalized":[{"db_name":"MESH","db_id":"D010554"}]},{"id":"14970","type":"Chemical","text":["clonidine"],"offsets":[[1291,1300]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]},{"id":"14971","type":"Chemical","text":["antidepressants"],"offsets":[[1425,1440]],"normalized":[{"db_name":"MESH","db_id":"D000928"}]},{"id":"14972","type":"Chemical","text":["TRI"],"offsets":[[1461,1464]],"normalized":[{"db_name":"MESH","db_id":"D014299"}]},{"id":"14973","type":"Chemical","text":["dopamine"],"offsets":[[1520,1528]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"14974","type":"Chemical","text":["antidepressants"],"offsets":[[1752,1767]],"normalized":[{"db_name":"MESH","db_id":"D000928"}]},{"id":"14975","type":"Chemical","text":["antidepressant"],"offsets":[[1805,1819]],"normalized":[{"db_name":"MESH","db_id":"D000928"}]}],"events":[],"coreferences":[],"relations":[{"id":"14976","type":"CID","arg1_id":"14962","arg2_id":"14961","normalized":[]},{"id":"14977","type":"CID","arg1_id":"14965","arg2_id":"14961","normalized":[]},{"id":"14978","type":"CID","arg1_id":"14957","arg2_id":"14958","normalized":[]},{"id":"14979","type":"CID","arg1_id":"14944","arg2_id":"14961","normalized":[]},{"id":"14980","type":"CID","arg1_id":"14946","arg2_id":"14961","normalized":[]},{"id":"14981","type":"CID","arg1_id":"14947","arg2_id":"14961","normalized":[]},{"id":"14982","type":"CID","arg1_id":"14953","arg2_id":"14961","normalized":[]},{"id":"14983","type":"CID","arg1_id":"14955","arg2_id":"14961","normalized":[]},{"id":"14984","type":"CID","arg1_id":"14956","arg2_id":"14961","normalized":[]},{"id":"14985","type":"CID","arg1_id":"14960","arg2_id":"14961","normalized":[]},{"id":"14986","type":"CID","arg1_id":"14967","arg2_id":"14961","normalized":[]},{"id":"14987","type":"CID","arg1_id":"14972","arg2_id":"14961","normalized":[]},{"id":"14988","type":"CID","arg1_id":"14963","arg2_id":"14961","normalized":[]}]}
{"id":"14989","document_id":"11431197","passages":[{"id":"14990","type":"title","text":["Ranitidine-induced acute interstitial nephritis in a cadaveric renal allograft."],"offsets":[[0,79]]},{"id":"14991","type":"abstract","text":["Ranitidine frequently is used for preventing peptic ulceration after renal transplantation. This drug occasionally has been associated with acute interstitial nephritis in native kidneys. There are no similar reports with renal transplantation. We report a case of ranitidine-induced acute interstitial nephritis in a recipient of a cadaveric renal allograft presenting with acute allograft dysfunction within 48 hours of exposure to the drug. The biopsy specimen showed pathognomonic features, including eosinophilic infiltration of the interstitial compartment. Allograft function improved rapidly and returned to baseline after stopping the drug."],"offsets":[[80,729]]}],"entities":[{"id":"14992","type":"Chemical","text":["Ranitidine"],"offsets":[[0,10]],"normalized":[{"db_name":"MESH","db_id":"D011899"}]},{"id":"14993","type":"Disease","text":["interstitial nephritis"],"offsets":[[25,47]],"normalized":[{"db_name":"MESH","db_id":"D009395"}]},{"id":"14994","type":"Chemical","text":["Ranitidine"],"offsets":[[80,90]],"normalized":[{"db_name":"MESH","db_id":"D011899"}]},{"id":"14995","type":"Disease","text":["interstitial nephritis"],"offsets":[[226,248]],"normalized":[{"db_name":"MESH","db_id":"D009395"}]},{"id":"14996","type":"Chemical","text":["ranitidine"],"offsets":[[345,355]],"normalized":[{"db_name":"MESH","db_id":"D011899"}]},{"id":"14997","type":"Disease","text":["interstitial nephritis"],"offsets":[[370,392]],"normalized":[{"db_name":"MESH","db_id":"D009395"}]}],"events":[],"coreferences":[],"relations":[{"id":"14998","type":"CID","arg1_id":"14992","arg2_id":"14993","normalized":[]},{"id":"14999","type":"CID","arg1_id":"14992","arg2_id":"14995","normalized":[]},{"id":"15000","type":"CID","arg1_id":"14992","arg2_id":"14997","normalized":[]},{"id":"15001","type":"CID","arg1_id":"14994","arg2_id":"14993","normalized":[]},{"id":"15002","type":"CID","arg1_id":"14994","arg2_id":"14995","normalized":[]},{"id":"15003","type":"CID","arg1_id":"14994","arg2_id":"14997","normalized":[]},{"id":"15004","type":"CID","arg1_id":"14996","arg2_id":"14993","normalized":[]},{"id":"15005","type":"CID","arg1_id":"14996","arg2_id":"14995","normalized":[]},{"id":"15006","type":"CID","arg1_id":"14996","arg2_id":"14997","normalized":[]}]}
{"id":"15007","document_id":"7449470","passages":[{"id":"15008","type":"title","text":["Late, late doxorubicin cardiotoxicity."],"offsets":[[0,38]]},{"id":"15009","type":"abstract","text":["Cardiac toxicity is a major complication which limits the use of adriamycin as a chemotherapeutic agent. Cardiomyopathy is frequent when the total dose exceeds 600 mg\/m2 and occurs within one to six months after cessation of therapy. A patient is reported who developed progressive cardiomyopathy two and one-half years after receiving 580 mg\/m2 which apparently represents late, late cardiotoxicity."],"offsets":[[39,439]]}],"entities":[{"id":"15010","type":"Chemical","text":["doxorubicin"],"offsets":[[11,22]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"15011","type":"Disease","text":["cardiotoxicity"],"offsets":[[23,37]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"15012","type":"Disease","text":["Cardiac toxicity"],"offsets":[[39,55]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"15013","type":"Chemical","text":["adriamycin"],"offsets":[[104,114]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"15014","type":"Disease","text":["Cardiomyopathy"],"offsets":[[144,158]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"15015","type":"Disease","text":["cardiomyopathy"],"offsets":[[321,335]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"15016","type":"Disease","text":["cardiotoxicity"],"offsets":[[424,438]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]}],"events":[],"coreferences":[],"relations":[{"id":"15017","type":"CID","arg1_id":"15010","arg2_id":"15014","normalized":[]},{"id":"15018","type":"CID","arg1_id":"15010","arg2_id":"15015","normalized":[]},{"id":"15019","type":"CID","arg1_id":"15013","arg2_id":"15014","normalized":[]},{"id":"15020","type":"CID","arg1_id":"15013","arg2_id":"15015","normalized":[]}]}
{"id":"15021","document_id":"8170551","passages":[{"id":"15022","type":"title","text":["Acetazolamide-induced nephrolithiasis: implications for treatment of neuromuscular disorders."],"offsets":[[0,93]]},{"id":"15023","type":"abstract","text":["Carbonic anhydrase inhibitors can cause nephrolithiasis. We studied 20 patients receiving long-term carbonic anhydrase inhibitor treatment for periodic paralysis and myotonia. Three patients on acetazolamide (15%) developed renal calculi. Extracorporeal lithotripsy successfully removed a renal calculus in one patient and surgery removed a staghorn calculus in another, permitting continued treatment. Renal function remained normal in all patients. Nephrolithiasis is a complication of acetazolamide but does not preclude its use."],"offsets":[[94,626]]}],"entities":[{"id":"15024","type":"Chemical","text":["Acetazolamide"],"offsets":[[0,13]],"normalized":[{"db_name":"MESH","db_id":"D000086"}]},{"id":"15025","type":"Disease","text":["nephrolithiasis"],"offsets":[[22,37]],"normalized":[{"db_name":"MESH","db_id":"D053040"}]},{"id":"15026","type":"Disease","text":["neuromuscular disorders"],"offsets":[[69,92]],"normalized":[{"db_name":"MESH","db_id":"D009468"}]},{"id":"15027","type":"Disease","text":["nephrolithiasis"],"offsets":[[134,149]],"normalized":[{"db_name":"MESH","db_id":"D053040"}]},{"id":"15028","type":"Disease","text":["paralysis"],"offsets":[[246,255]],"normalized":[{"db_name":"MESH","db_id":"D010243"}]},{"id":"15029","type":"Disease","text":["myotonia"],"offsets":[[260,268]],"normalized":[{"db_name":"MESH","db_id":"D009222"}]},{"id":"15030","type":"Chemical","text":["acetazolamide"],"offsets":[[288,301]],"normalized":[{"db_name":"MESH","db_id":"D000086"}]},{"id":"15031","type":"Disease","text":["renal calculi"],"offsets":[[318,331]],"normalized":[{"db_name":"MESH","db_id":"D007669"}]},{"id":"15032","type":"Disease","text":["renal calculus"],"offsets":[[383,397]],"normalized":[{"db_name":"MESH","db_id":"D007669"}]},{"id":"15033","type":"Disease","text":["calculus"],"offsets":[[444,452]],"normalized":[{"db_name":"MESH","db_id":"D002137"}]},{"id":"15034","type":"Disease","text":["Nephrolithiasis"],"offsets":[[545,560]],"normalized":[{"db_name":"MESH","db_id":"D053040"}]},{"id":"15035","type":"Chemical","text":["acetazolamide"],"offsets":[[582,595]],"normalized":[{"db_name":"MESH","db_id":"D000086"}]}],"events":[],"coreferences":[],"relations":[{"id":"15036","type":"CID","arg1_id":"15024","arg2_id":"15031","normalized":[]},{"id":"15037","type":"CID","arg1_id":"15024","arg2_id":"15032","normalized":[]},{"id":"15038","type":"CID","arg1_id":"15030","arg2_id":"15031","normalized":[]},{"id":"15039","type":"CID","arg1_id":"15030","arg2_id":"15032","normalized":[]},{"id":"15040","type":"CID","arg1_id":"15035","arg2_id":"15031","normalized":[]},{"id":"15041","type":"CID","arg1_id":"15035","arg2_id":"15032","normalized":[]}]}
{"id":"15042","document_id":"2476560","passages":[{"id":"15043","type":"title","text":["Is the treatment of scabies hazardous?"],"offsets":[[0,38]]},{"id":"15044","type":"abstract","text":["Treatment for scabies is usually initiated by general practitioners; most consider lindane (gamma benzene hexachloride) the treatment of choice. Lindane is also widely used as an agricultural and industrial pesticide, and as a result the toxic profile of this insecticide is well understood. Evidence is accumulating that lindane can be toxic to the central nervous system and may be associated with aplastic anaemia. Preparations containing lindane continue to be sold over the counter and may represent a hazard to poorly informed patients. This literature review suggests that general practitioners should prescribe scabicides with increased caution for certain at-risk groups, and give adequate warnings regarding potential toxicity."],"offsets":[[39,776]]}],"entities":[{"id":"15045","type":"Disease","text":["scabies"],"offsets":[[20,27]],"normalized":[{"db_name":"MESH","db_id":"D012532"}]},{"id":"15046","type":"Disease","text":["scabies"],"offsets":[[53,60]],"normalized":[{"db_name":"MESH","db_id":"D012532"}]},{"id":"15047","type":"Chemical","text":["lindane"],"offsets":[[122,129]],"normalized":[{"db_name":"MESH","db_id":"D001556"}]},{"id":"15048","type":"Chemical","text":["gamma benzene hexachloride"],"offsets":[[131,157]],"normalized":[{"db_name":"MESH","db_id":"D001556"}]},{"id":"15049","type":"Chemical","text":["Lindane"],"offsets":[[184,191]],"normalized":[{"db_name":"MESH","db_id":"D001556"}]},{"id":"15050","type":"Chemical","text":["lindane"],"offsets":[[361,368]],"normalized":[{"db_name":"MESH","db_id":"D001556"}]},{"id":"15051","type":"Disease","text":["toxic to the central nervous system"],"offsets":[[376,411]],"normalized":[{"db_name":"MESH","db_id":"D002493"}]},{"id":"15052","type":"Disease","text":["aplastic anaemia"],"offsets":[[439,455]],"normalized":[{"db_name":"MESH","db_id":"D000741"}]},{"id":"15053","type":"Chemical","text":["lindane"],"offsets":[[481,488]],"normalized":[{"db_name":"MESH","db_id":"D001556"}]},{"id":"15054","type":"Disease","text":["toxicity"],"offsets":[[767,775]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]}],"events":[],"coreferences":[],"relations":[{"id":"15055","type":"CID","arg1_id":"15047","arg2_id":"15052","normalized":[]},{"id":"15056","type":"CID","arg1_id":"15048","arg2_id":"15052","normalized":[]},{"id":"15057","type":"CID","arg1_id":"15049","arg2_id":"15052","normalized":[]},{"id":"15058","type":"CID","arg1_id":"15050","arg2_id":"15052","normalized":[]},{"id":"15059","type":"CID","arg1_id":"15053","arg2_id":"15052","normalized":[]},{"id":"15060","type":"CID","arg1_id":"15047","arg2_id":"15051","normalized":[]},{"id":"15061","type":"CID","arg1_id":"15048","arg2_id":"15051","normalized":[]},{"id":"15062","type":"CID","arg1_id":"15049","arg2_id":"15051","normalized":[]},{"id":"15063","type":"CID","arg1_id":"15050","arg2_id":"15051","normalized":[]},{"id":"15064","type":"CID","arg1_id":"15053","arg2_id":"15051","normalized":[]}]}
{"id":"15065","document_id":"19803309","passages":[{"id":"15066","type":"title","text":["Anaesthetists' nightmare: masseter spasm after induction in an undiagnosed case of myotonia congenita."],"offsets":[[0,102]]},{"id":"15067","type":"abstract","text":["We report an undiagnosed case of myotonia congenita in a 24-year-old previously healthy primigravida, who developed life threatening masseter spasm following a standard dose of intravenous suxamethonium for induction of anaesthesia. Neither the patient nor the anaesthetist was aware of the diagnosis before this potentially lethal complication occurred."],"offsets":[[103,457]]}],"entities":[{"id":"15068","type":"Disease","text":["masseter spasm"],"offsets":[[26,40]],"normalized":[{"db_name":"MESH","db_id":"D014313"}]},{"id":"15069","type":"Disease","text":["myotonia congenita"],"offsets":[[83,101]],"normalized":[{"db_name":"MESH","db_id":"D009224"}]},{"id":"15070","type":"Disease","text":["myotonia congenita"],"offsets":[[136,154]],"normalized":[{"db_name":"MESH","db_id":"D009224"}]},{"id":"15071","type":"Disease","text":["masseter spasm"],"offsets":[[236,250]],"normalized":[{"db_name":"MESH","db_id":"D014313"}]},{"id":"15072","type":"Chemical","text":["suxamethonium"],"offsets":[[292,305]],"normalized":[{"db_name":"MESH","db_id":"D013390"}]}],"events":[],"coreferences":[],"relations":[{"id":"15073","type":"CID","arg1_id":"15072","arg2_id":"15068","normalized":[]},{"id":"15074","type":"CID","arg1_id":"15072","arg2_id":"15071","normalized":[]}]}
{"id":"15075","document_id":"18821488","passages":[{"id":"15076","type":"title","text":["Toxicity in rhesus monkeys following administration of the 8-aminoquinoline 8-[(4-amino-l-methylbutyl)amino]- 5-(l-hexyloxy)-6-methoxy-4-methylquinoline (WR242511)."],"offsets":[[0,164]]},{"id":"15077","type":"abstract","text":["INTRODUCTION: Many substances that form methemoglobin (MHb) effectively counter cyanide (CN) toxicity. Although MHb formers are generally applied as treatments for CN poisoning, it has been proposed that a stable, long-acting MHb former could serve as a CN pretreatment. Using this rationale, the 8-aminoquinoline WR242511, a potent long-lasting MHb former in rodents and beagle dogs, was studied in the rhesus monkey for advanced development as a potential CN pretreatment. METHODS: In this study, WR242511 was administered intravenously (IV) in 2 female and 4 male rhesus monkeys in doses of 3.5 and\/or 7.0 mg\/kg; a single male also received WR242511 orally (PO) at 7.0 mg\/kg. Health status and MHb levels were monitored following exposure. RESULTS: The selected doses of WR242511, which produced significant methemoglobinemia in beagle dogs in earlier studies conducted elsewhere, produced very little MHb (mean < 2.0%) in the rhesus monkey. Furthermore, transient hemoglobinuria was noted approximately 60 minutes postinjection of WR242511 (3.5 or 7.0 mg\/kg), and 2 lethalities occurred (one IV and one PO) following the 7.0 mg\/kg dose. Myoglobinuria was also observed following the 7.0 mg\/kg dose. Histopathology analyses in the 2 animals that died revealed liver and kidney toxicity, with greater severity in the orally-treated animal. CONCLUSIONS: These data demonstrate direct and\/or indirect drug-induced toxicity. It is concluded that WR242511 should not be pursued as a pretreatment for CN poisoning unless the anti-CN characteristics of this compound can be successfully dissociated from those producing undesirable toxicity."],"offsets":[[165,1802]]}],"entities":[{"id":"15078","type":"Disease","text":["Toxicity"],"offsets":[[0,8]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"15079","type":"Chemical","text":["8-aminoquinoline"],"offsets":[[59,75]],"normalized":[{"db_name":"MESH","db_id":"C080436"}]},{"id":"15080","type":"Chemical","text":["8-[(4-amino-l-methylbutyl)amino]- 5-(l-hexyloxy)-6-methoxy-4-methylquinoline"],"offsets":[[76,152]],"normalized":[{"db_name":"MESH","db_id":"C068820"}]},{"id":"15081","type":"Chemical","text":["WR242511"],"offsets":[[154,162]],"normalized":[{"db_name":"MESH","db_id":"C068820"}]},{"id":"15082","type":"Disease","text":["toxicity"],"offsets":[[258,266]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"15083","type":"Disease","text":["poisoning"],"offsets":[[332,341]],"normalized":[{"db_name":"MESH","db_id":"D011041"}]},{"id":"15084","type":"Chemical","text":["8-aminoquinoline"],"offsets":[[462,478]],"normalized":[{"db_name":"MESH","db_id":"C080436"}]},{"id":"15085","type":"Chemical","text":["WR242511"],"offsets":[[479,487]],"normalized":[{"db_name":"MESH","db_id":"C068820"}]},{"id":"15086","type":"Chemical","text":["WR242511"],"offsets":[[664,672]],"normalized":[{"db_name":"MESH","db_id":"C068820"}]},{"id":"15087","type":"Chemical","text":["WR242511"],"offsets":[[809,817]],"normalized":[{"db_name":"MESH","db_id":"C068820"}]},{"id":"15088","type":"Chemical","text":["WR242511"],"offsets":[[939,947]],"normalized":[{"db_name":"MESH","db_id":"C068820"}]},{"id":"15089","type":"Disease","text":["methemoglobinemia"],"offsets":[[976,993]],"normalized":[{"db_name":"MESH","db_id":"D008708"}]},{"id":"15090","type":"Disease","text":["hemoglobinuria"],"offsets":[[1133,1147]],"normalized":[{"db_name":"MESH","db_id":"D006456"}]},{"id":"15091","type":"Chemical","text":["WR242511"],"offsets":[[1200,1208]],"normalized":[{"db_name":"MESH","db_id":"C068820"}]},{"id":"15092","type":"Disease","text":["Myoglobinuria"],"offsets":[[1306,1319]],"normalized":[{"db_name":"MESH","db_id":"D009212"}]},{"id":"15093","type":"Disease","text":["liver and kidney toxicity"],"offsets":[[1428,1453]],"normalized":[{"db_name":"MESH","db_id":"D056486"},{"db_name":"MESH","db_id":"D007674"}]},{"id":"15094","type":"Disease","text":["liver","toxicity"],"offsets":[[1428,1433],[1445,1453]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"15095","type":"Disease","text":["kidney 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{"id":"15148","document_id":"8372922","passages":[{"id":"15149","type":"title","text":["Neuroplasticity of the adult primate auditory cortex following cochlear hearing loss."],"offsets":[[0,85]]},{"id":"15150","type":"abstract","text":["Tonotopic organization is an essential feature of the primary auditory area (A1) of primate cortex. In A1 of macaque monkeys, low frequencies are represented rostrolaterally and high frequencies are represented caudomedially. The purpose of this study was to determine if changes occur in this tonotopic organization following cochlear hearing loss. Under anesthesia, the superior temporal gyrus of adult macaque monkeys was exposed, and the tonotopic organization of A1 was mapped using conventional microelectrode recording techniques. Following recovery, the monkeys were selectively deafened for high frequencies using kanamycin and furosemide. The actual frequencies deafened were determined by the loss of tone-burst elicited auditory brainstem responses. Three months after deafening, A1 was remapped. Postmortem cytoarchitectural features identifying A1 were correlated with the electrophysiologic data. The results indicate that the deprived area of A1 undergoes extensive reorganization and becomes responsive to intact cochlear frequencies. The region of cortex that represents the low frequencies was not obviously affected by the cochlear hearing loss."],"offsets":[[86,1251]]}],"entities":[{"id":"15151","type":"Disease","text":["hearing loss"],"offsets":[[72,84]],"normalized":[{"db_name":"MESH","db_id":"D034381"}]},{"id":"15152","type":"Disease","text":["hearing loss"],"offsets":[[422,434]],"normalized":[{"db_name":"MESH","db_id":"D034381"}]},{"id":"15153","type":"Chemical","text":["kanamycin"],"offsets":[[709,718]],"normalized":[{"db_name":"MESH","db_id":"D007612"}]},{"id":"15154","type":"Chemical","text":["furosemide"],"offsets":[[723,733]],"normalized":[{"db_name":"MESH","db_id":"D005665"}]},{"id":"15155","type":"Disease","text":["hearing loss"],"offsets":[[1238,1250]],"normalized":[{"db_name":"MESH","db_id":"D034381"}]}],"events":[],"coreferences":[],"relations":[{"id":"15156","type":"CID","arg1_id":"15154","arg2_id":"15151","normalized":[]},{"id":"15157","type":"CID","arg1_id":"15154","arg2_id":"15152","normalized":[]},{"id":"15158","type":"CID","arg1_id":"15154","arg2_id":"15155","normalized":[]},{"id":"15159","type":"CID","arg1_id":"15153","arg2_id":"15151","normalized":[]},{"id":"15160","type":"CID","arg1_id":"15153","arg2_id":"15152","normalized":[]},{"id":"15161","type":"CID","arg1_id":"15153","arg2_id":"15155","normalized":[]}]}
{"id":"15162","document_id":"9195768","passages":[{"id":"15163","type":"title","text":["The site of common side effects of sumatriptan."],"offsets":[[0,47]]},{"id":"15164","type":"abstract","text":["Atypical sensations following the use of subcutaneous sumatriptan are common, but of uncertain origin. They are almost always benign, but can be mistaken for a serious adverse event by the patient. Two patients are presented with tingling or burning sensations limited to areas of heat exposure or sunburn. In these individuals, side effects are most likely generated superficially in the skin."],"offsets":[[48,442]]}],"entities":[{"id":"15165","type":"Chemical","text":["sumatriptan"],"offsets":[[35,46]],"normalized":[{"db_name":"MESH","db_id":"D018170"}]},{"id":"15166","type":"Disease","text":["Atypical sensations"],"offsets":[[48,67]],"normalized":[{"db_name":"MESH","db_id":"D010292"}]},{"id":"15167","type":"Chemical","text":["sumatriptan"],"offsets":[[102,113]],"normalized":[{"db_name":"MESH","db_id":"D018170"}]},{"id":"15168","type":"Disease","text":["tingling or burning sensations"],"offsets":[[278,308]],"normalized":[{"db_name":"MESH","db_id":"D010292"}]},{"id":"15169","type":"Disease","text":["sunburn"],"offsets":[[346,353]],"normalized":[{"db_name":"MESH","db_id":"D013471"}]}],"events":[],"coreferences":[],"relations":[{"id":"15170","type":"CID","arg1_id":"15165","arg2_id":"15166","normalized":[]},{"id":"15171","type":"CID","arg1_id":"15165","arg2_id":"15168","normalized":[]},{"id":"15172","type":"CID","arg1_id":"15167","arg2_id":"15166","normalized":[]},{"id":"15173","type":"CID","arg1_id":"15167","arg2_id":"15168","normalized":[]}]}
{"id":"15174","document_id":"15338796","passages":[{"id":"15175","type":"title","text":["Tremor side effects of salbutamol, quantified by a laser pointer technique."],"offsets":[[0,75]]},{"id":"15176","type":"abstract","text":["OBJECTIVE: To study tremor side effects of salbutamol an easily applicable, quick and low-priced method is needed. A new method using a commercially available, pen-shaped laser pointer was developed. Aim of the study was to determine sensitivity, reproducibility, reference values and the agreement with a questionnaire. METHODS: Tremor was measured using a laser pointer technique. To determine sensitivity we assessed tremor in 44 patients with obstructive lung disease after administration of cumulative doses of salbutamol. Subjects were asked to aim at the centre of a target, subdivided in concentric circles, from 5 m distance. The circle in which the participant succeeded to aim was recorded in millimetres radius. In another series of measurements, reproducibility and reference values of the tremor was assessed in 65 healthy subjects in three sessions, at 9 a.m., 4 p.m. and 9 a.m., respectively, 1 week later. Postural tremor was measured with the arm horizontally outstretched rest tremor with the arm supported by an armrest and finally tremor was measured after holding a 2-kg weight until exhaustion. Inter-observer variability was measured in a series of 10 healthy subjects. Tremor was measured simultaneously by two independent observers. RESULTS: Salbutamol significantly increased tremor severity in patients in a dose-dependent way. Within healthy adults no age-dependency could be found (b = 0.262 mm\/year; P = 0.72). There was no agreement between the questionnaire and tremor severity (r = 0.093; P = 0.53). Postural tremor showed no significant difference between the first and third session (P = 0.07). Support of the arm decreased tremor severity, exhaustion increased tremor severity significantly. A good agreement was found between two independent observers (interclass correlation coefficient 0.72). DISCUSSION: Quantifying tremor by using an inexpensive laser pointer is, with the exception of children (<12 years) a sensitive and reproducible method."],"offsets":[[76,2061]]}],"entities":[{"id":"15177","type":"Disease","text":["Tremor"],"offsets":[[0,6]],"normalized":[{"db_name":"MESH","db_id":"D014202"}]},{"id":"15178","type":"Chemical","text":["salbutamol"],"offsets":[[23,33]],"normalized":[{"db_name":"MESH","db_id":"D000420"}]},{"id":"15179","type":"Disease","text":["tremor"],"offsets":[[96,102]],"normalized":[{"db_name":"MESH","db_id":"D014202"}]},{"id":"15180","type":"Chemical","text":["salbutamol"],"offsets":[[119,129]],"normalized":[{"db_name":"MESH","db_id":"D000420"}]},{"id":"15181","type":"Disease","text":["Tremor"],"offsets":[[406,412]],"normalized":[{"db_name":"MESH","db_id":"D014202"}]},{"id":"15182","type":"Disease","text":["tremor"],"offsets":[[496,502]],"normalized":[{"db_name":"MESH","db_id":"D014202"}]},{"id":"15183","type":"Disease","text":["obstructive lung disease"],"offsets":[[523,547]],"normalized":[{"db_name":"MESH","db_id":"D008173"}]},{"id":"15184","type":"Chemical","text":["salbutamol"],"offsets":[[592,602]],"normalized":[{"db_name":"MESH","db_id":"D000420"}]},{"id":"15185","type":"Disease","text":["tremor"],"offsets":[[879,885]],"normalized":[{"db_name":"MESH","db_id":"D014202"}]},{"id":"15186","type":"Disease","text":["tremor"],"offsets":[[1008,1014]],"normalized":[{"db_name":"MESH","db_id":"D014202"}]},{"id":"15187","type":"Disease","text":["tremor"],"offsets":[[1072,1078]],"normalized":[{"db_name":"MESH","db_id":"D014202"}]},{"id":"15188","type":"Disease","text":["tremor"],"offsets":[[1128,1134]],"normalized":[{"db_name":"MESH","db_id":"D014202"}]},{"id":"15189","type":"Disease","text":["Tremor"],"offsets":[[1270,1276]],"normalized":[{"db_name":"MESH","db_id":"D014202"}]},{"id":"15190","type":"Chemical","text":["Salbutamol"],"offsets":[[1344,1354]],"normalized":[{"db_name":"MESH","db_id":"D000420"}]},{"id":"15191","type":"Disease","text":["tremor"],"offsets":[[1379,1385]],"normalized":[{"db_name":"MESH","db_id":"D014202"}]},{"id":"15192","type":"Disease","text":["tremor"],"offsets":[[1571,1577]],"normalized":[{"db_name":"MESH","db_id":"D014202"}]},{"id":"15193","type":"Disease","text":["tremor"],"offsets":[[1619,1625]],"normalized":[{"db_name":"MESH","db_id":"D014202"}]},{"id":"15194","type":"Disease","text":["tremor"],"offsets":[[1736,1742]],"normalized":[{"db_name":"MESH","db_id":"D014202"}]},{"id":"15195","type":"Disease","text":["tremor"],"offsets":[[1774,1780]],"normalized":[{"db_name":"MESH","db_id":"D014202"}]},{"id":"15196","type":"Disease","text":["tremor"],"offsets":[[1933,1939]],"normalized":[{"db_name":"MESH","db_id":"D014202"}]}],"events":[],"coreferences":[],"relations":[{"id":"15197","type":"CID","arg1_id":"15178","arg2_id":"15177","normalized":[]},{"id":"15198","type":"CID","arg1_id":"15178","arg2_id":"15179","normalized":[]},{"id":"15199","type":"CID","arg1_id":"15178","arg2_id":"15181","normalized":[]},{"id":"15200","type":"CID","arg1_id":"15178","arg2_id":"15182","normalized":[]},{"id":"15201","type":"CID","arg1_id":"15178","arg2_id":"15185","normalized":[]},{"id":"15202","type":"CID","arg1_id":"15178","arg2_id":"15186","normalized":[]},{"id":"15203","type":"CID","arg1_id":"15178","arg2_id":"15187","normalized":[]},{"id":"15204","type":"CID","arg1_id":"15178","arg2_id":"15188","normalized":[]},{"id":"15205","type":"CID","arg1_id":"15178","arg2_id":"15189","normalized":[]},{"id":"15206","type":"CID","arg1_id":"15178","arg2_id":"15191","normalized":[]},{"id":"15207","type":"CID","arg1_id":"15178","arg2_id":"15192","normalized":[]},{"id":"15208","type":"CID","arg1_id":"15178","arg2_id":"15193","normalized":[]},{"id":"15209","type":"CID","arg1_id":"15178","arg2_id":"15194","normalized":[]},{"id":"15210","type":"CID","arg1_id":"15178","arg2_id":"15195","normalized":[]},{"id":"15211","type":"CID","arg1_id":"15178","arg2_id":"15196","normalized":[]},{"id":"15212","type":"CID","arg1_id":"15180","arg2_id":"15177","normalized":[]},{"id":"15213","type":"CID","arg1_id":"15180","arg2_id":"15179","normalized":[]},{"id":"15214","type":"CID","arg1_id":"15180","arg2_id":"15181","normalized":[]},{"id":"15215","type":"CID","arg1_id":"15180","arg2_id":"15182","normalized":[]},{"id":"15216","type":"CID","arg1_id":"15180","arg2_id":"15185","normalized":[]},{"id":"15217","type":"CID","arg1_id":"15180","arg2_id":"15186","normalized":[]},{"id":"15218","type":"CID","arg1_id":"15180","arg2_id":"15187","normalized":[]},{"id":"15219","type":"CID","arg1_id":"15180","arg2_id":"15188","normalized":[]},{"id":"15220","type":"CID","arg1_id":"15180","arg2_id":"15189","normalized":[]},{"id":"15221","type":"CID","arg1_id":"15180","arg2_id":"15191","normalized":[]},{"id":"15222","type":"CID","arg1_id":"15180","arg2_id":"15192","normalized":[]},{"id":"15223","type":"CID","arg1_id":"15180","arg2_id":"15193","normalized":[]},{"id":"15224","type":"CID","arg1_id":"15180","arg2_id":"15194","normalized":[]},{"id":"15225","type":"CID","arg1_id":"15180","arg2_id":"15195","normalized":[]},{"id":"15226","type":"CID","arg1_id":"15180","arg2_id":"15196","normalized":[]},{"id":"15227","type":"CID","arg1_id":"15184","arg2_id":"15177","normalized":[]},{"id":"15228","type":"CID","arg1_id":"15184","arg2_id":"15179","normalized":[]},{"id":"15229","type":"CID","arg1_id":"15184","arg2_id":"15181","normalized":[]},{"id":"15230","type":"CID","arg1_id":"15184","arg2_id":"15182","normalized":[]},{"id":"15231","type":"CID","arg1_id":"15184","arg2_id":"15185","normalized":[]},{"id":"15232","type":"CID","arg1_id":"15184","arg2_id":"15186","normalized":[]},{"id":"15233","type":"CID","arg1_id":"15184","arg2_id":"15187","normalized":[]},{"id":"15234","type":"CID","arg1_id":"15184","arg2_id":"15188","normalized":[]},{"id":"15235","type":"CID","arg1_id":"15184","arg2_id":"15189","normalized":[]},{"id":"15236","type":"CID","arg1_id":"15184","arg2_id":"15191","normalized":[]},{"id":"15237","type":"CID",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{"id":"15257","document_id":"12627929","passages":[{"id":"15258","type":"title","text":["Increased frequency of venous thromboembolism with the combination of docetaxel and thalidomide in patients with metastatic androgen-independent prostate cancer."],"offsets":[[0,161]]},{"id":"15259","type":"abstract","text":["STUDY OBJECTIVE: To evaluate the frequency of venous thromboembolism (VTE) in patients with advanced androgen-independent prostate cancer who were treated with docetaxel alone or in combination with thalidomide. DESIGN: Retrospective analysis of a randomized phase II trial. SETTING: National Institutes of Health clinical research center. PATIENTS: Seventy men, aged 50-80 years, with advanced androgen-independent prostate cancer. INTERVENTION: Each patient received either intravenous docetaxel 30 mg\/m2\/week for 3 consecutive weeks, followed by 1 week off, or the combination of continuous oral thalidomide 200 mg every evening plus the same docetaxel regimen. This 4-week cycle was repeated until there was evidence of excessive toxicity or disease progression. MEASUREMENTS AND MAIN RESULTS: None of 23 patients who received docetaxel alone developed VTE, whereas 9 of 47 patients (19%) who received docetaxel plus thalidomide developed VTE (p=0.025). CONCLUSION: The addition of thalidomide to docetaxel in the treatment of prostate cancer significantly increases the frequency of VTE. Clinicians should be aware of this potential complication when adding thalidomide to chemotherapeutic regimens."],"offsets":[[162,1366]]}],"entities":[{"id":"15260","type":"Disease","text":["venous thromboembolism"],"offsets":[[23,45]],"normalized":[{"db_name":"MESH","db_id":"D054556"}]},{"id":"15261","type":"Chemical","text":["docetaxel"],"offsets":[[70,79]],"normalized":[{"db_name":"MESH","db_id":"C067311"}]},{"id":"15262","type":"Chemical","text":["thalidomide"],"offsets":[[84,95]],"normalized":[{"db_name":"MESH","db_id":"D013792"}]},{"id":"15263","type":"Disease","text":["prostate cancer"],"offsets":[[145,160]],"normalized":[{"db_name":"MESH","db_id":"D011471"}]},{"id":"15264","type":"Disease","text":["venous thromboembolism"],"offsets":[[208,230]],"normalized":[{"db_name":"MESH","db_id":"D054556"}]},{"id":"15265","type":"Disease","text":["VTE"],"offsets":[[232,235]],"normalized":[{"db_name":"MESH","db_id":"D054556"}]},{"id":"15266","type":"Disease","text":["prostate 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{"id":"15362","document_id":"6634932","passages":[{"id":"15363","type":"title","text":["Sublingual absorption of the quaternary ammonium antiarrhythmic agent, UM-272."],"offsets":[[0,78]]},{"id":"15364","type":"abstract","text":["UM-272 (N,N-dimethylpropranolol), a quaternary antiarrhythmic agent, was administered sublingually to dogs with ouabain-induced ventricular tachycardias. Both anti-arrhythmic efficacy and bioavailability were compared to oral drug. Sublingual UM-272 converted ventricular tachycardia to sinus rhythm in all 5 dogs. The area under the plasma concentration time curve at 90 min was 4-12 times greater than for oral drug, suggesting the existence of an absorption-limiting process in the intestine, and providing an alternate form of administration for quaternary drugs."],"offsets":[[79,646]]}],"entities":[{"id":"15365","type":"Chemical","text":["quaternary ammonium"],"offsets":[[29,48]],"normalized":[{"db_name":"MESH","db_id":"D000644"}]},{"id":"15366","type":"Chemical","text":["UM-272"],"offsets":[[71,77]],"normalized":[{"db_name":"MESH","db_id":"C002616"}]},{"id":"15367","type":"Chemical","text":["UM-272"],"offsets":[[79,85]],"normalized":[{"db_name":"MESH","db_id":"C002616"}]},{"id":"15368","type":"Chemical","text":["N,N-dimethylpropranolol"],"offsets":[[87,110]],"normalized":[{"db_name":"MESH","db_id":"C002616"}]},{"id":"15369","type":"Chemical","text":["ouabain"],"offsets":[[191,198]],"normalized":[{"db_name":"MESH","db_id":"D010042"}]},{"id":"15370","type":"Disease","text":["ventricular tachycardias"],"offsets":[[207,231]],"normalized":[{"db_name":"MESH","db_id":"D017180"}]},{"id":"15371","type":"Chemical","text":["UM-272"],"offsets":[[322,328]],"normalized":[{"db_name":"MESH","db_id":"C002616"}]},{"id":"15372","type":"Disease","text":["ventricular tachycardia"],"offsets":[[339,362]],"normalized":[{"db_name":"MESH","db_id":"D017180"}]}],"events":[],"coreferences":[],"relations":[{"id":"15373","type":"CID","arg1_id":"15369","arg2_id":"15370","normalized":[]},{"id":"15374","type":"CID","arg1_id":"15369","arg2_id":"15372","normalized":[]}]}
{"id":"15375","document_id":"18791946","passages":[{"id":"15376","type":"title","text":["Severe thrombocytopenia and haemolytic anaemia associated with ciprofloxacin: a case report with fatal outcome."],"offsets":[[0,111]]},{"id":"15377","type":"abstract","text":["Haematological adverse reactions associated with fatal outcome are rare during treatment with ciprofloxacin. A 30-year old Caucasian man reported with abdominal pain and jaundice after 3-day administration of oral ciprofloxacin for a suspect of urinary tract infection. Clinical evaluations suggested an initial diagnosis of severe thrombocytopenia and haemolysis. The patient progressively developed petechiae and purpura on thorax and lower limbs. Despite pharmacological and supportive interventions, laboratory parameters worsened and the patient died 17 hours after admission. An accurate autopsy revealed most organs with diffuse petechial haemorrhages. No signs of bone marrow depression were found. No thrombi or signs of microangiopathies were observed in arterial vessels. Blood and urine cultures did not show any bacterial growth. This case report shows that ciprofloxacin may precipitate life-threatening thrombocytopenia and haemolytic anaemia, even in the early phases of treatment and without apparent previous exposures."],"offsets":[[112,1149]]}],"entities":[{"id":"15378","type":"Disease","text":["thrombocytopenia"],"offsets":[[7,23]],"normalized":[{"db_name":"MESH","db_id":"D013921"}]},{"id":"15379","type":"Disease","text":["haemolytic anaemia"],"offsets":[[28,46]],"normalized":[{"db_name":"MESH","db_id":"D000743"}]},{"id":"15380","type":"Chemical","text":["ciprofloxacin"],"offsets":[[63,76]],"normalized":[{"db_name":"MESH","db_id":"D002939"}]},{"id":"15381","type":"Chemical","text":["ciprofloxacin"],"offsets":[[206,219]],"normalized":[{"db_name":"MESH","db_id":"D002939"}]},{"id":"15382","type":"Disease","text":["abdominal 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{"id":"15433","document_id":"17344566","passages":[{"id":"15434","type":"title","text":["Simvastatin-induced bilateral leg compartment syndrome and myonecrosis associated with hypothyroidism."],"offsets":[[0,102]]},{"id":"15435","type":"abstract","text":["A 54-year-old hypothyroid male taking thyroxine and simvastatin presented with bilateral leg compartment syndrome and myonecrosis. Urgent fasciotomies were performed and the patient made an uneventful recovery with the withdrawal of simvastatin. It is likely that this complication will be seen more often with the increased worldwide use of this drug and its approval for all arteriopathic patients."],"offsets":[[103,503]]}],"entities":[{"id":"15436","type":"Chemical","text":["Simvastatin"],"offsets":[[0,11]],"normalized":[{"db_name":"MESH","db_id":"D019821"}]},{"id":"15437","type":"Disease","text":["compartment syndrome"],"offsets":[[34,54]],"normalized":[{"db_name":"MESH","db_id":"D003161"}]},{"id":"15438","type":"Disease","text":["myonecrosis"],"offsets":[[59,70]],"normalized":[{"db_name":"MESH","db_id":"D009135"}]},{"id":"15439","type":"Disease","text":["hypothyroidism"],"offsets":[[87,101]],"normalized":[{"db_name":"MESH","db_id":"D007037"}]},{"id":"15440","type":"Disease","text":["hypothyroid"],"offsets":[[117,128]],"normalized":[{"db_name":"MESH","db_id":"D007037"}]},{"id":"15441","type":"Chemical","text":["thyroxine"],"offsets":[[141,150]],"normalized":[{"db_name":"MESH","db_id":"D013974"}]},{"id":"15442","type":"Chemical","text":["simvastatin"],"offsets":[[155,166]],"normalized":[{"db_name":"MESH","db_id":"D019821"}]},{"id":"15443","type":"Disease","text":["compartment syndrome"],"offsets":[[196,216]],"normalized":[{"db_name":"MESH","db_id":"D003161"}]},{"id":"15444","type":"Disease","text":["myonecrosis"],"offsets":[[221,232]],"normalized":[{"db_name":"MESH","db_id":"D009135"}]},{"id":"15445","type":"Chemical","text":["simvastatin"],"offsets":[[336,347]],"normalized":[{"db_name":"MESH","db_id":"D019821"}]},{"id":"15446","type":"Disease","text":["arteriopathic"],"offsets":[[480,493]],"normalized":[{"db_name":"MESH","db_id":"D014652"}]}],"events":[],"coreferences":[],"relations":[{"id":"15447","type":"CID","arg1_id":"15436","arg2_id":"15437","normalized":[]},{"id":"15448","type":"CID","arg1_id":"15436","arg2_id":"15443","normalized":[]},{"id":"15449","type":"CID","arg1_id":"15442","arg2_id":"15437","normalized":[]},{"id":"15450","type":"CID","arg1_id":"15442","arg2_id":"15443","normalized":[]},{"id":"15451","type":"CID","arg1_id":"15445","arg2_id":"15437","normalized":[]},{"id":"15452","type":"CID","arg1_id":"15445","arg2_id":"15443","normalized":[]}]}
{"id":"15453","document_id":"9293063","passages":[{"id":"15454","type":"title","text":["Bile duct hamartoma occurring in association with long-term treatment with danazol."],"offsets":[[0,83]]},{"id":"15455","type":"abstract","text":["We report a case of bile duct hamartoma which developed in a patient who had been on long-term danazol treatment. Such patients should be under close follow-up, preferably with periodic ultrasound examination of the liver. If the patient develops a liver mass, because of non-specific clinical features and imaging appearances, biopsy may be the only way to achieve a definitive diagnosis."],"offsets":[[84,473]]}],"entities":[{"id":"15456","type":"Disease","text":["Bile duct hamartoma"],"offsets":[[0,19]],"normalized":[{"db_name":"MESH","db_id":"D001650"},{"db_name":"MESH","db_id":"D006222"}]},{"id":"15457","type":"Disease","text":["Bile duct hamartoma"],"offsets":[[0,19]],"normalized":[{"db_name":"MESH","db_id":"D001650"}]},{"id":"15458","type":"Disease","text":["hamartoma"],"offsets":[[10,19]],"normalized":[{"db_name":"MESH","db_id":"D006222"}]},{"id":"15459","type":"Chemical","text":["danazol"],"offsets":[[75,82]],"normalized":[{"db_name":"MESH","db_id":"D003613"}]},{"id":"15460","type":"Disease","text":["bile duct hamartoma"],"offsets":[[104,123]],"normalized":[{"db_name":"MESH","db_id":"D001650"},{"db_name":"MESH","db_id":"D006222"}]},{"id":"15461","type":"Disease","text":["bile duct hamartoma"],"offsets":[[104,123]],"normalized":[{"db_name":"MESH","db_id":"D001650"}]},{"id":"15462","type":"Disease","text":["hamartoma"],"offsets":[[114,123]],"normalized":[{"db_name":"MESH","db_id":"D006222"}]},{"id":"15463","type":"Chemical","text":["danazol"],"offsets":[[179,186]],"normalized":[{"db_name":"MESH","db_id":"D003613"}]},{"id":"15464","type":"Disease","text":["liver mass"],"offsets":[[333,343]],"normalized":[{"db_name":"MESH","db_id":"D008107"}]}],"events":[],"coreferences":[],"relations":[{"id":"15465","type":"CID","arg1_id":"15459","arg2_id":"15456","normalized":[]},{"id":"15466","type":"CID","arg1_id":"15459","arg2_id":"15457","normalized":[]},{"id":"15467","type":"CID","arg1_id":"15459","arg2_id":"15460","normalized":[]},{"id":"15468","type":"CID","arg1_id":"15459","arg2_id":"15461","normalized":[]},{"id":"15469","type":"CID","arg1_id":"15463","arg2_id":"15456","normalized":[]},{"id":"15470","type":"CID","arg1_id":"15463","arg2_id":"15457","normalized":[]},{"id":"15471","type":"CID","arg1_id":"15463","arg2_id":"15460","normalized":[]},{"id":"15472","type":"CID","arg1_id":"15463","arg2_id":"15461","normalized":[]},{"id":"15473","type":"CID","arg1_id":"15459","arg2_id":"15456","normalized":[]},{"id":"15474","type":"CID","arg1_id":"15459","arg2_id":"15458","normalized":[]},{"id":"15475","type":"CID","arg1_id":"15459","arg2_id":"15460","normalized":[]},{"id":"15476","type":"CID","arg1_id":"15459","arg2_id":"15462","normalized":[]},{"id":"15477","type":"CID","arg1_id":"15463","arg2_id":"15456","normalized":[]},{"id":"15478","type":"CID","arg1_id":"15463","arg2_id":"15458","normalized":[]},{"id":"15479","type":"CID","arg1_id":"15463","arg2_id":"15460","normalized":[]},{"id":"15480","type":"CID","arg1_id":"15463","arg2_id":"15462","normalized":[]}]}
{"id":"15481","document_id":"1728522","passages":[{"id":"15482","type":"title","text":["Granulomatous hepatitis due to combination of amoxicillin and clavulanic acid."],"offsets":[[0,78]]},{"id":"15483","type":"abstract","text":["We report the case of a patient with amoxicillin-clavulanic acid-induced hepatitis with histologic multiple granulomas. This type of lesion broadens the spectrum of liver injury due to this drug combination, mainly represented by a benign cholestatic syndrome. The association of granulomas and eosinophilia favor an immunoallergic mechanism. As penicillin derivatives and amoxicillin alone are known to induce such types of lesions, the amoxicillin component, with or without a potentiating effect of clavulanic acid, might have a major role."],"offsets":[[79,622]]}],"entities":[{"id":"15484","type":"Disease","text":["Granulomatous hepatitis"],"offsets":[[0,23]],"normalized":[{"db_name":"MESH","db_id":"D006099"},{"db_name":"MESH","db_id":"D056486"}]},{"id":"15485","type":"Disease","text":["Granulomatous"],"offsets":[[0,13]],"normalized":[{"db_name":"MESH","db_id":"D006099"}]},{"id":"15486","type":"Disease","text":["hepatitis"],"offsets":[[14,23]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"15487","type":"Chemical","text":["combination of amoxicillin and clavulanic acid"],"offsets":[[31,77]],"normalized":[{"db_name":"MESH","db_id":"D019980"}]},{"id":"15488","type":"Chemical","text":["amoxicillin-clavulanic acid"],"offsets":[[116,143]],"normalized":[{"db_name":"MESH","db_id":"D019980"}]},{"id":"15489","type":"Disease","text":["hepatitis"],"offsets":[[152,161]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"15490","type":"Disease","text":["granulomas"],"offsets":[[187,197]],"normalized":[{"db_name":"MESH","db_id":"D006099"}]},{"id":"15491","type":"Disease","text":["liver injury"],"offsets":[[244,256]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"15492","type":"Disease","text":["cholestatic syndrome"],"offsets":[[318,338]],"normalized":[{"db_name":"MESH","db_id":"D002779"}]},{"id":"15493","type":"Disease","text":["granulomas"],"offsets":[[359,369]],"normalized":[{"db_name":"MESH","db_id":"D006099"}]},{"id":"15494","type":"Disease","text":["eosinophilia"],"offsets":[[374,386]],"normalized":[{"db_name":"MESH","db_id":"D004802"}]},{"id":"15495","type":"Chemical","text":["penicillin"],"offsets":[[425,435]],"normalized":[{"db_name":"MESH","db_id":"D010406"}]},{"id":"15496","type":"Chemical","text":["amoxicillin"],"offsets":[[452,463]],"normalized":[{"db_name":"MESH","db_id":"D000658"}]},{"id":"15497","type":"Chemical","text":["amoxicillin"],"offsets":[[517,528]],"normalized":[{"db_name":"MESH","db_id":"D000658"}]},{"id":"15498","type":"Chemical","text":["clavulanic acid"],"offsets":[[581,596]],"normalized":[{"db_name":"MESH","db_id":"D019818"}]}],"events":[],"coreferences":[],"relations":[{"id":"15499","type":"CID","arg1_id":"15487","arg2_id":"15484","normalized":[]},{"id":"15500","type":"CID","arg1_id":"15487","arg2_id":"15486","normalized":[]},{"id":"15501","type":"CID","arg1_id":"15487","arg2_id":"15489","normalized":[]},{"id":"15502","type":"CID","arg1_id":"15487","arg2_id":"15491","normalized":[]},{"id":"15503","type":"CID","arg1_id":"15488","arg2_id":"15484","normalized":[]},{"id":"15504","type":"CID","arg1_id":"15488","arg2_id":"15486","normalized":[]},{"id":"15505","type":"CID","arg1_id":"15488","arg2_id":"15489","normalized":[]},{"id":"15506","type":"CID","arg1_id":"15488","arg2_id":"15491","normalized":[]},{"id":"15507","type":"CID","arg1_id":"15487","arg2_id":"15484","normalized":[]},{"id":"15508","type":"CID","arg1_id":"15487","arg2_id":"15485","normalized":[]},{"id":"15509","type":"CID","arg1_id":"15487","arg2_id":"15490","normalized":[]},{"id":"15510","type":"CID","arg1_id":"15487","arg2_id":"15493","normalized":[]},{"id":"15511","type":"CID","arg1_id":"15488","arg2_id":"15484","normalized":[]},{"id":"15512","type":"CID","arg1_id":"15488","arg2_id":"15485","normalized":[]},{"id":"15513","type":"CID","arg1_id":"15488","arg2_id":"15490","normalized":[]},{"id":"15514","type":"CID","arg1_id":"15488","arg2_id":"15493","normalized":[]},{"id":"15515","type":"CID","arg1_id":"15487","arg2_id":"15492","normalized":[]},{"id":"15516","type":"CID","arg1_id":"15488","arg2_id":"15492","normalized":[]}]}
{"id":"15517","document_id":"10807237","passages":[{"id":"15518","type":"title","text":["Intracranial aneurysms and cocaine abuse: analysis of prognostic indicators."],"offsets":[[0,76]]},{"id":"15519","type":"abstract","text":["OBJECTIVE: The outcome of subarachnoid hemorrhage associated with cocaine abuse is reportedly poor. However, no study in the literature has reported the use of a statistical model to analyze the variables that influence outcome. METHODS: A review of admissions during a 6-year period revealed 14 patients with cocaine-related aneurysms. This group was compared with a control group of 135 patients with ruptured aneurysms and no history of cocaine abuse. Age at presentation, time of ictus after intoxication, Hunt and Hess grade of subarachnoid hemorrhage, size of the aneurysm, location of the aneurysm, and the Glasgow Outcome Scale score were assessed and compared. RESULTS: The patients in the study group were significantly younger than the patients in the control group (P < 0.002). In patients in the study group, all aneurysms were located in the anterior circulation. The majority of these aneurysms were smaller than those of the control group (8 +\/- 6.08 mm versus 11 +\/- 5.4 mm; P = 0.05). The differences in mortality and morbidity between the two groups were not significant. Hunt and Hess grade (P < 0.005) and age (P < 0.007) were significant predictors of outcome for the patients with cocaine-related aneurysms. CONCLUSION: Cocaine use predisposed aneurysmal rupture at a significantly earlier age and in much smaller aneurysms. Contrary to the published literature, this group did reasonably well with aggressive management."],"offsets":[[77,1521]]}],"entities":[{"id":"15520","type":"Disease","text":["Intracranial aneurysms"],"offsets":[[0,22]],"normalized":[{"db_name":"MESH","db_id":"D002532"}]},{"id":"15521","type":"Disease","text":["cocaine abuse"],"offsets":[[27,40]],"normalized":[{"db_name":"MESH","db_id":"D019970"}]},{"id":"15522","type":"Disease","text":["subarachnoid hemorrhage"],"offsets":[[103,126]],"normalized":[{"db_name":"MESH","db_id":"D013345"}]},{"id":"15523","type":"Disease","text":["cocaine abuse"],"offsets":[[143,156]],"normalized":[{"db_name":"MESH","db_id":"D019970"}]},{"id":"15524","type":"Chemical","text":["cocaine"],"offsets":[[387,394]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"15525","type":"Disease","text":["aneurysms"],"offsets":[[403,412]],"normalized":[{"db_name":"MESH","db_id":"D000783"}]},{"id":"15526","type":"Disease","text":["ruptured aneurysms"],"offsets":[[480,498]],"normalized":[{"db_name":"MESH","db_id":"D017542"}]},{"id":"15527","type":"Disease","text":["cocaine abuse"],"offsets":[[517,530]],"normalized":[{"db_name":"MESH","db_id":"D019970"}]},{"id":"15528","type":"Disease","text":["subarachnoid hemorrhage"],"offsets":[[610,633]],"normalized":[{"db_name":"MESH","db_id":"D013345"}]},{"id":"15529","type":"Disease","text":["aneurysm"],"offsets":[[647,655]],"normalized":[{"db_name":"MESH","db_id":"D000783"}]},{"id":"15530","type":"Disease","text":["aneurysm"],"offsets":[[673,681]],"normalized":[{"db_name":"MESH","db_id":"D000783"}]},{"id":"15531","type":"Disease","text":["aneurysms"],"offsets":[[903,912]],"normalized":[{"db_name":"MESH","db_id":"D000783"}]},{"id":"15532","type":"Disease","text":["aneurysms"],"offsets":[[977,986]],"normalized":[{"db_name":"MESH","db_id":"D000783"}]},{"id":"15533","type":"Chemical","text":["cocaine"],"offsets":[[1281,1288]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"15534","type":"Disease","text":["aneurysms"],"offsets":[[1297,1306]],"normalized":[{"db_name":"MESH","db_id":"D000783"}]},{"id":"15535","type":"Chemical","text":["Cocaine"],"offsets":[[1320,1327]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"15536","type":"Disease","text":["aneurysmal rupture"],"offsets":[[1344,1362]],"normalized":[{"db_name":"MESH","db_id":"D017542"}]},{"id":"15537","type":"Disease","text":["aneurysms"],"offsets":[[1414,1423]],"normalized":[{"db_name":"MESH","db_id":"D000783"}]}],"events":[],"coreferences":[],"relations":[{"id":"15538","type":"CID","arg1_id":"15524","arg2_id":"15526","normalized":[]},{"id":"15539","type":"CID","arg1_id":"15524","arg2_id":"15536","normalized":[]},{"id":"15540","type":"CID","arg1_id":"15533","arg2_id":"15526","normalized":[]},{"id":"15541","type":"CID","arg1_id":"15533","arg2_id":"15536","normalized":[]},{"id":"15542","type":"CID","arg1_id":"15535","arg2_id":"15526","normalized":[]},{"id":"15543","type":"CID","arg1_id":"15535","arg2_id":"15536","normalized":[]}]}
{"id":"15544","document_id":"12536034","passages":[{"id":"15545","type":"title","text":["Anti-epileptic drugs-induced de novo absence seizures."],"offsets":[[0,54]]},{"id":"15546","type":"abstract","text":["The authors present three patients with de novo absence epilepsy after administration of carbamazepine and vigabatrin. Despite the underlying diseases, the prognosis for drug-induced de novo absence seizure is good because it subsides rapidly after discontinuing the use of the offending drugs. The gamma-aminobutyric acid-transmitted thalamocortical circuitry accounts for a major part of the underlying neurophysiology of the absence epilepsy. Because drug-induced de novo absence seizure is rare, pro-absence drugs can only be considered a promoting factor. The underlying epileptogenecity of the patients or the synergistic effects of the accompanying drugs is required to trigger the de novo absence seizure. The possibility of drug-induced aggravation should be considered whenever an unexpected increase in seizure frequency and\/or new seizure types appear following a change in drug treatment. By understanding the underlying mechanism of absence epilepsy, we can avoid the inappropriate use of anticonvulsants in children with epilepsy and prevent drug-induced absence seizures."],"offsets":[[55,1142]]}],"entities":[{"id":"15547","type":"Disease","text":["epileptic"],"offsets":[[5,14]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"15548","type":"Disease","text":["absence seizures"],"offsets":[[37,53]],"normalized":[{"db_name":"MESH","db_id":"D004832"}]},{"id":"15549","type":"Disease","text":["absence epilepsy"],"offsets":[[103,119]],"normalized":[{"db_name":"MESH","db_id":"D004832"}]},{"id":"15550","type":"Chemical","text":["carbamazepine"],"offsets":[[144,157]],"normalized":[{"db_name":"MESH","db_id":"D002220"}]},{"id":"15551","type":"Chemical","text":["vigabatrin"],"offsets":[[162,172]],"normalized":[{"db_name":"MESH","db_id":"D020888"}]},{"id":"15552","type":"Disease","text":["absence seizure"],"offsets":[[246,261]],"normalized":[{"db_name":"MESH","db_id":"D004832"}]},{"id":"15553","type":"Chemical","text":["gamma-aminobutyric acid"],"offsets":[[354,377]],"normalized":[{"db_name":"MESH","db_id":"D005680"}]},{"id":"15554","type":"Disease","text":["absence epilepsy"],"offsets":[[483,499]],"normalized":[{"db_name":"MESH","db_id":"D004832"}]},{"id":"15555","type":"Disease","text":["absence seizure"],"offsets":[[530,545]],"normalized":[{"db_name":"MESH","db_id":"D004832"}]},{"id":"15556","type":"Disease","text":["absence seizure"],"offsets":[[752,767]],"normalized":[{"db_name":"MESH","db_id":"D004832"}]},{"id":"15557","type":"Disease","text":["seizure"],"offsets":[[869,876]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"15558","type":"Disease","text":["seizure"],"offsets":[[898,905]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"15559","type":"Disease","text":["absence epilepsy"],"offsets":[[1002,1018]],"normalized":[{"db_name":"MESH","db_id":"D004832"}]},{"id":"15560","type":"Disease","text":["epilepsy"],"offsets":[[1091,1099]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"15561","type":"Disease","text":["absence seizures"],"offsets":[[1125,1141]],"normalized":[{"db_name":"MESH","db_id":"D004832"}]}],"events":[],"coreferences":[],"relations":[{"id":"15562","type":"CID","arg1_id":"15551","arg2_id":"15548","normalized":[]},{"id":"15563","type":"CID","arg1_id":"15551","arg2_id":"15549","normalized":[]},{"id":"15564","type":"CID","arg1_id":"15551","arg2_id":"15552","normalized":[]},{"id":"15565","type":"CID","arg1_id":"15551","arg2_id":"15554","normalized":[]},{"id":"15566","type":"CID","arg1_id":"15551","arg2_id":"15555","normalized":[]},{"id":"15567","type":"CID","arg1_id":"15551","arg2_id":"15556","normalized":[]},{"id":"15568","type":"CID","arg1_id":"15551","arg2_id":"15559","normalized":[]},{"id":"15569","type":"CID","arg1_id":"15551","arg2_id":"15561","normalized":[]},{"id":"15570","type":"CID","arg1_id":"15550","arg2_id":"15548","normalized":[]},{"id":"15571","type":"CID","arg1_id":"15550","arg2_id":"15549","normalized":[]},{"id":"15572","type":"CID","arg1_id":"15550","arg2_id":"15552","normalized":[]},{"id":"15573","type":"CID","arg1_id":"15550","arg2_id":"15554","normalized":[]},{"id":"15574","type":"CID","arg1_id":"15550","arg2_id":"15555","normalized":[]},{"id":"15575","type":"CID","arg1_id":"15550","arg2_id":"15556","normalized":[]},{"id":"15576","type":"CID","arg1_id":"15550","arg2_id":"15559","normalized":[]},{"id":"15577","type":"CID","arg1_id":"15550","arg2_id":"15561","normalized":[]}]}
{"id":"15578","document_id":"7234705","passages":[{"id":"15579","type":"title","text":["Procainamide-induced polymorphous ventricular tachycardia."],"offsets":[[0,58]]},{"id":"15580","type":"abstract","text":["Seven cases of procainamide-induced polymorphous ventricular tachycardia are presented. In four patients, polymorphous ventricular tachycardia appeared after intravenous administration of 200 to 400 mg of procainamide for the treatment of sustained ventricular tachycardia. In the remaining three patients, procainamide was administered orally for treatment of chronic premature ventricular contractions or atrial flutter. These patients had Q-T prolongation and recurrent syncope due to polymorphous ventricular tachycardia. In four patients, the arrhythmia was rapidly diagnosed and treated with disappearance of further episodes of the arrhythmia. In two patients, the arrhythmia degenerated into irreversible ventricular fibrillation and both patients died. In the seventh patient, a permanent ventricular pacemaker was inserted and, despite continuation of procainamide therapy, polymorphous ventricular tachycardia did not reoccur. These seven cases demonstrate that procainamide can produce an acquired prolonged Q-T syndrome with polymorphous ventricular tachycardia."],"offsets":[[59,1134]]}],"entities":[{"id":"15581","type":"Chemical","text":["Procainamide"],"offsets":[[0,12]],"normalized":[{"db_name":"MESH","db_id":"D011342"}]},{"id":"15582","type":"Disease","text":["ventricular tachycardia"],"offsets":[[34,57]],"normalized":[{"db_name":"MESH","db_id":"D017180"}]},{"id":"15583","type":"Chemical","text":["procainamide"],"offsets":[[74,86]],"normalized":[{"db_name":"MESH","db_id":"D011342"}]},{"id":"15584","type":"Disease","text":["ventricular tachycardia"],"offsets":[[108,131]],"normalized":[{"db_name":"MESH","db_id":"D017180"}]},{"id":"15585","type":"Disease","text":["ventricular tachycardia"],"offsets":[[178,201]],"normalized":[{"db_name":"MESH","db_id":"D017180"}]},{"id":"15586","type":"Chemical","text":["procainamide"],"offsets":[[264,276]],"normalized":[{"db_name":"MESH","db_id":"D011342"}]},{"id":"15587","type":"Disease","text":["ventricular tachycardia"],"offsets":[[308,331]],"normalized":[{"db_name":"MESH","db_id":"D017180"}]},{"id":"15588","type":"Chemical","text":["procainamide"],"offsets":[[366,378]],"normalized":[{"db_name":"MESH","db_id":"D011342"}]},{"id":"15589","type":"Disease","text":["premature ventricular contractions"],"offsets":[[428,462]],"normalized":[{"db_name":"MESH","db_id":"D018879"}]},{"id":"15590","type":"Disease","text":["atrial flutter"],"offsets":[[466,480]],"normalized":[{"db_name":"MESH","db_id":"D001282"}]},{"id":"15591","type":"Disease","text":["Q-T prolongation"],"offsets":[[501,517]],"normalized":[{"db_name":"MESH","db_id":"D008133"}]},{"id":"15592","type":"Disease","text":["syncope"],"offsets":[[532,539]],"normalized":[{"db_name":"MESH","db_id":"D013575"}]},{"id":"15593","type":"Disease","text":["ventricular tachycardia"],"offsets":[[560,583]],"normalized":[{"db_name":"MESH","db_id":"D017180"}]},{"id":"15594","type":"Disease","text":["arrhythmia"],"offsets":[[607,617]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"15595","type":"Disease","text":["arrhythmia"],"offsets":[[698,708]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"15596","type":"Disease","text":["arrhythmia"],"offsets":[[731,741]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"15597","type":"Disease","text":["ventricular fibrillation"],"offsets":[[772,796]],"normalized":[{"db_name":"MESH","db_id":"D014693"}]},{"id":"15598","type":"Chemical","text":["procainamide"],"offsets":[[921,933]],"normalized":[{"db_name":"MESH","db_id":"D011342"}]},{"id":"15599","type":"Disease","text":["ventricular tachycardia"],"offsets":[[956,979]],"normalized":[{"db_name":"MESH","db_id":"D017180"}]},{"id":"15600","type":"Chemical","text":["procainamide"],"offsets":[[1032,1044]],"normalized":[{"db_name":"MESH","db_id":"D011342"}]},{"id":"15601","type":"Disease","text":["prolonged Q-T syndrome"],"offsets":[[1069,1091]],"normalized":[{"db_name":"MESH","db_id":"D008133"}]},{"id":"15602","type":"Disease","text":["ventricular tachycardia"],"offsets":[[1110,1133]],"normalized":[{"db_name":"MESH","db_id":"D017180"}]}],"events":[],"coreferences":[],"relations":[{"id":"15603","type":"CID","arg1_id":"15581","arg2_id":"15582","normalized":[]},{"id":"15604","type":"CID","arg1_id":"15581","arg2_id":"15584","normalized":[]},{"id":"15605","type":"CID","arg1_id":"15581","arg2_id":"15585","normalized":[]},{"id":"15606","type":"CID","arg1_id":"15581","arg2_id":"15587","normalized":[]},{"id":"15607","type":"CID","arg1_id":"15581","arg2_id":"15593","normalized":[]},{"id":"15608","type":"CID","arg1_id":"15581","arg2_id":"15599","normalized":[]},{"id":"15609","type":"CID","arg1_id":"15581","arg2_id":"15602","normalized":[]},{"id":"15610","type":"CID","arg1_id":"15583","arg2_id":"15582","normalized":[]},{"id":"15611","type":"CID","arg1_id":"15583","arg2_id":"15584","normalized":[]},{"id":"15612","type":"CID","arg1_id":"15583","arg2_id":"15585","normalized":[]},{"id":"15613","type":"CID","arg1_id":"15583","arg2_id":"15587","normalized":[]},{"id":"15614","type":"CID","arg1_id":"15583","arg2_id":"15593","normalized":[]},{"id":"15615","type":"CID","arg1_id":"15583","arg2_id":"15599","normalized":[]},{"id":"15616","type":"CID","arg1_id":"15583","arg2_id":"15602","normalized":[]},{"id":"15617","type":"CID","arg1_id":"15586","arg2_id":"15582","normalized":[]},{"id":"15618","type":"CID","arg1_id":"15586","arg2_id":"15584","normalized":[]},{"id":"15619","type":"CID","arg1_id":"15586","arg2_id":"15585","normalized":[]},{"id":"15620","type":"CID","arg1_id":"15586","arg2_id":"15587","normalized":[]},{"id":"15621","type":"CID","arg1_id":"15586","arg2_id":"15593","normalized":[]},{"id":"15622","type":"CID","arg1_id":"15586","arg2_id":"15599","normalized":[]},{"id":"15623","type":"CID","arg1_id":"15586","arg2_id":"15602","normalized":[]},{"id":"15624","type":"CID","arg1_id":"15588","arg2_id":"15582","normalized":[]},{"id":"15625","type":"CID","arg1_id":"15588","arg2_id":"15584","normalized":[]},{"id":"15626","type":"CID","arg1_id":"15588","arg2_id":"15585","normalized":[]},{"id":"15627","type":"CID","arg1_id":"15588","arg2_id":"15587","normalized":[]},{"id":"15628","type":"CID","arg1_id":"15588","arg2_id":"15593","normalized":[]},{"id":"15629","type":"CID","arg1_id":"15588","arg2_id":"15599","normalized":[]},{"id":"15630","type":"CID","arg1_id":"15588","arg2_id":"15602","normalized":[]},{"id":"15631","type":"CID","arg1_id":"15598","arg2_id":"15582","normalized":[]},{"id":"15632","type":"CID","arg1_id":"15598","arg2_id":"15584","normalized":[]},{"id":"15633","type":"CID","arg1_id":"15598","arg2_id":"15585","normalized":[]},{"id":"15634","type":"CID","arg1_id":"15598","arg2_id":"15587","normalized":[]},{"id":"15635","type":"CID","arg1_id":"15598","arg2_id":"15593","normalized":[]},{"id":"15636","type":"CID","arg1_id":"15598","arg2_id":"15599","normalized":[]},{"id":"15637","type":"CID","arg1_id":"15598","arg2_id":"15602","normalized":[]},{"id":"15638","type":"CID","arg1_id":"15600","arg2_id":"15582","normalized":[]},{"id":"15639","type":"CID","arg1_id":"15600","arg2_id":"15584","normalized":[]},{"id":"15640","type":"CID","arg1_id":"15600","arg2_id":"15585","normalized":[]},{"id":"15641","type":"CID","arg1_id":"15600","arg2_id":"15587","normalized":[]},{"id":"15642","type":"CID","arg1_id":"15600","arg2_id":"15593","normalized":[]},{"id":"15643","type":"CID","arg1_id":"15600","arg2_id":"15599","normalized":[]},{"id":"15644","type":"CID","arg1_id":"15600","arg2_id":"15602","normalized":[]}]}
{"id":"15645","document_id":"8955532","passages":[{"id":"15646","type":"title","text":["Role of activation of bradykinin B2 receptors in disruption of the blood-brain barrier during acute hypertension."],"offsets":[[0,113]]},{"id":"15647","type":"abstract","text":["Cellular mechanisms which account for disruption the blood-brain barrier during acute hypertension are not clear. The goal of this study was to determine the role of synthesis\/release of bradykinin to activate B2 receptors in disruption of the blood-brain barrier during acute hypertension. Permeability of the blood-brain barrier was quantitated by clearance of fluorescent-labeled dextran before and during phenylephrine-induced acute hypertension in rats treated with vehicle and Hoe-140 (0.1 microM). Phenylephrine infusion increased arterial pressure, arteriolar diameter and clearance of fluorescent dextran by a similar magnitude in both groups. These findings suggest that disruption of the blood-brain barrier during acute hypertension is not related to the synthesis\/release of bradykinin to activate B2 receptors."],"offsets":[[114,938]]}],"entities":[{"id":"15648","type":"Chemical","text":["bradykinin"],"offsets":[[22,32]],"normalized":[{"db_name":"MESH","db_id":"D001920"}]},{"id":"15649","type":"Disease","text":["hypertension"],"offsets":[[100,112]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"15650","type":"Disease","text":["hypertension"],"offsets":[[200,212]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"15651","type":"Chemical","text":["bradykinin"],"offsets":[[301,311]],"normalized":[{"db_name":"MESH","db_id":"D001920"}]},{"id":"15652","type":"Disease","text":["hypertension"],"offsets":[[391,403]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"15653","type":"Chemical","text":["dextran"],"offsets":[[497,504]],"normalized":[{"db_name":"MESH","db_id":"D003911"}]},{"id":"15654","type":"Chemical","text":["phenylephrine"],"offsets":[[523,536]],"normalized":[{"db_name":"MESH","db_id":"D010656"}]},{"id":"15655","type":"Disease","text":["hypertension"],"offsets":[[551,563]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"15656","type":"Chemical","text":["Hoe-140"],"offsets":[[597,604]],"normalized":[{"db_name":"MESH","db_id":"C065679"}]},{"id":"15657","type":"Chemical","text":["Phenylephrine"],"offsets":[[619,632]],"normalized":[{"db_name":"MESH","db_id":"D010656"}]},{"id":"15658","type":"Chemical","text":["dextran"],"offsets":[[720,727]],"normalized":[{"db_name":"MESH","db_id":"D003911"}]},{"id":"15659","type":"Disease","text":["hypertension"],"offsets":[[846,858]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"15660","type":"Chemical","text":["bradykinin"],"offsets":[[902,912]],"normalized":[{"db_name":"MESH","db_id":"D001920"}]}],"events":[],"coreferences":[],"relations":[{"id":"15661","type":"CID","arg1_id":"15654","arg2_id":"15649","normalized":[]},{"id":"15662","type":"CID","arg1_id":"15654","arg2_id":"15650","normalized":[]},{"id":"15663","type":"CID","arg1_id":"15654","arg2_id":"15652","normalized":[]},{"id":"15664","type":"CID","arg1_id":"15654","arg2_id":"15655","normalized":[]},{"id":"15665","type":"CID","arg1_id":"15654","arg2_id":"15659","normalized":[]},{"id":"15666","type":"CID","arg1_id":"15657","arg2_id":"15649","normalized":[]},{"id":"15667","type":"CID","arg1_id":"15657","arg2_id":"15650","normalized":[]},{"id":"15668","type":"CID","arg1_id":"15657","arg2_id":"15652","normalized":[]},{"id":"15669","type":"CID","arg1_id":"15657","arg2_id":"15655","normalized":[]},{"id":"15670","type":"CID","arg1_id":"15657","arg2_id":"15659","normalized":[]}]}
{"id":"15671","document_id":"2578334","passages":[{"id":"15672","type":"title","text":["5-azacytidine potentiates initiation induced by carcinogens in rat liver."],"offsets":[[0,73]]},{"id":"15673","type":"abstract","text":["To test the validity of the hypothesis that hypomethylation of DNA plays an important role in the initiation of carcinogenic process, 5-azacytidine (5-AzC) (10 mg\/kg), an inhibitor of DNA methylation, was given to rats during the phase of repair synthesis induced by the three carcinogens, benzo[a]-pyrene (200 mg\/kg), N-methyl-N-nitrosourea (60 mg\/kg) and 1,2-dimethylhydrazine (1,2-DMH) (100 mg\/kg). The initiated hepatocytes in the liver were assayed as the gamma-glutamyltransferase (gamma-GT) positive foci formed following a 2-week selection regimen consisting of dietary 0.02% 2-acetylaminofluorene coupled with a necrogenic dose of CCl4. The results obtained indicate that with all three carcinogens, administration of 5-AzC during repair synthesis increased the incidence of initiated hepatocytes, for example 10-20 foci\/cm2 in 5-AzC and carcinogen-treated rats compared with 3-5 foci\/cm2 in rats treated with carcinogen only. Administration of [3H]-5-azadeoxycytidine during the repair synthesis induced by 1,2-DMH further showed that 0.019 mol % of cytosine residues in DNA were substituted by the analogue, indicating that incorporation of 5-AzC occurs during repair synthesis. In the absence of the carcinogen, 5-AzC given after a two thirds partial hepatectomy, when its incorporation should be maximum, failed to induce any gamma-GT positive foci. The results suggest that hypomethylation of DNA per se may not be sufficient for initiation. Perhaps two events might be necessary for initiation, the first caused by the carcinogen and a second involving hypomethylation of DNA."],"offsets":[[74,1665]]}],"entities":[{"id":"15674","type":"Chemical","text":["5-azacytidine"],"offsets":[[0,13]],"normalized":[{"db_name":"MESH","db_id":"D001374"}]},{"id":"15675","type":"Disease","text":["initiation induced by carcinogens"],"offsets":[[26,59]],"normalized":[{"db_name":"MESH","db_id":"D011230"}]},{"id":"15676","type":"Disease","text":["initiation of carcinogenic process"],"offsets":[[172,206]],"normalized":[{"db_name":"MESH","db_id":"D011230"}]},{"id":"15677","type":"Chemical","text":["5-azacytidine"],"offsets":[[208,221]],"normalized":[{"db_name":"MESH","db_id":"D001374"}]},{"id":"15678","type":"Chemical","text":["5-AzC"],"offsets":[[223,228]],"normalized":[{"db_name":"MESH","db_id":"D001374"}]},{"id":"15679","type":"Chemical","text":["benzo[a]-pyrene"],"offsets":[[364,379]],"normalized":[{"db_name":"MESH","db_id":"D001564"}]},{"id":"15680","type":"Chemical","text":["N-methyl-N-nitrosourea"],"offsets":[[393,415]],"normalized":[{"db_name":"MESH","db_id":"D008770"}]},{"id":"15681","type":"Chemical","text":["1,2-dimethylhydrazine"],"offsets":[[431,452]],"normalized":[{"db_name":"MESH","db_id":"D019813"}]},{"id":"15682","type":"Chemical","text":["1,2-DMH"],"offsets":[[454,461]],"normalized":[{"db_name":"MESH","db_id":"D019813"}]},{"id":"15683","type":"Chemical","text":["2-acetylaminofluorene"],"offsets":[[658,679]],"normalized":[{"db_name":"MESH","db_id":"D015073"}]},{"id":"15684","type":"Chemical","text":["CCl4"],"offsets":[[714,718]],"normalized":[{"db_name":"MESH","db_id":"D002251"}]},{"id":"15685","type":"Chemical","text":["5-AzC"],"offsets":[[801,806]],"normalized":[{"db_name":"MESH","db_id":"D001374"}]},{"id":"15686","type":"Chemical","text":["5-AzC"],"offsets":[[911,916]],"normalized":[{"db_name":"MESH","db_id":"D001374"}]},{"id":"15687","type":"Chemical","text":["[3H]-5-azadeoxycytidine"],"offsets":[[1028,1051]],"normalized":[{"db_name":"MESH","db_id":"C014347"}]},{"id":"15688","type":"Chemical","text":["1,2-DMH"],"offsets":[[1091,1098]],"normalized":[{"db_name":"MESH","db_id":"D019813"}]},{"id":"15689","type":"Chemical","text":["cytosine"],"offsets":[[1134,1142]],"normalized":[{"db_name":"MESH","db_id":"D003596"}]},{"id":"15690","type":"Chemical","text":["5-AzC"],"offsets":[[1226,1231]],"normalized":[{"db_name":"MESH","db_id":"D001374"}]},{"id":"15691","type":"Chemical","text":["5-AzC"],"offsets":[[1298,1303]],"normalized":[{"db_name":"MESH","db_id":"D001374"}]}],"events":[],"coreferences":[],"relations":[{"id":"15692","type":"CID","arg1_id":"15683","arg2_id":"15675","normalized":[]},{"id":"15693","type":"CID","arg1_id":"15683","arg2_id":"15676","normalized":[]},{"id":"15694","type":"CID","arg1_id":"15679","arg2_id":"15675","normalized":[]},{"id":"15695","type":"CID","arg1_id":"15679","arg2_id":"15676","normalized":[]},{"id":"15696","type":"CID","arg1_id":"15684","arg2_id":"15675","normalized":[]},{"id":"15697","type":"CID","arg1_id":"15684","arg2_id":"15676","normalized":[]},{"id":"15698","type":"CID","arg1_id":"15674","arg2_id":"15675","normalized":[]},{"id":"15699","type":"CID","arg1_id":"15674","arg2_id":"15676","normalized":[]},{"id":"15700","type":"CID","arg1_id":"15677","arg2_id":"15675","normalized":[]},{"id":"15701","type":"CID","arg1_id":"15677","arg2_id":"15676","normalized":[]},{"id":"15702","type":"CID","arg1_id":"15678","arg2_id":"15675","normalized":[]},{"id":"15703","type":"CID","arg1_id":"15678","arg2_id":"15676","normalized":[]},{"id":"15704","type":"CID","arg1_id":"15685","arg2_id":"15675","normalized":[]},{"id":"15705","type":"CID","arg1_id":"15685","arg2_id":"15676","normalized":[]},{"id":"15706","type":"CID","arg1_id":"15686","arg2_id":"15675","normalized":[]},{"id":"15707","type":"CID","arg1_id":"15686","arg2_id":"15676","normalized":[]},{"id":"15708","type":"CID","arg1_id":"15690","arg2_id":"15675","normalized":[]},{"id":"15709","type":"CID","arg1_id":"15690","arg2_id":"15676","normalized":[]},{"id":"15710","type":"CID","arg1_id":"15691","arg2_id":"15675","normalized":[]},{"id":"15711","type":"CID","arg1_id":"15691","arg2_id":"15676","normalized":[]},{"id":"15712","type":"CID","arg1_id":"15681","arg2_id":"15675","normalized":[]},{"id":"15713","type":"CID","arg1_id":"15681","arg2_id":"15676","normalized":[]},{"id":"15714","type":"CID","arg1_id":"15682","arg2_id":"15675","normalized":[]},{"id":"15715","type":"CID","arg1_id":"15682","arg2_id":"15676","normalized":[]},{"id":"15716","type":"CID","arg1_id":"15688","arg2_id":"15675","normalized":[]},{"id":"15717","type":"CID","arg1_id":"15688","arg2_id":"15676","normalized":[]},{"id":"15718","type":"CID","arg1_id":"15680","arg2_id":"15675","normalized":[]},{"id":"15719","type":"CID","arg1_id":"15680","arg2_id":"15676","normalized":[]}]}
{"id":"15720","document_id":"11532387","passages":[{"id":"15721","type":"title","text":["Withdrawal-emergent rabbit syndrome during dose reduction of risperidone."],"offsets":[[0,73]]},{"id":"15722","type":"abstract","text":["Rabbit syndrome (RS) is a rare extrapyramidal side effect caused by prolonged neuroleptic medication. Here we present a case of withdrawal-emergent RS, which is the first of its kind to be reported. The patient developed RS during dose reduction of risperidone. The symptom was treated successfully with trihexyphenidyl anticholinergic therapy. The underlying mechanism of withdrawal-emergent RS in the present case may have been related to the pharmacological profile of risperidone, a serotonin-dopamine antagonist, suggesting the pathophysiologic influence of the serotonin system in the development of RS."],"offsets":[[74,683]]}],"entities":[{"id":"15723","type":"Disease","text":["Withdrawal-emergent rabbit syndrome"],"offsets":[[0,35]],"normalized":[{"db_name":"MESH","db_id":"D013375"},{"db_name":"MESH","db_id":"D001480"}]},{"id":"15724","type":"Disease","text":["Withdrawal","syndrome"],"offsets":[[0,10],[27,35]],"normalized":[{"db_name":"MESH","db_id":"D013375"}]},{"id":"15725","type":"Disease","text":["emergent rabbit syndrome"],"offsets":[[11,35]],"normalized":[{"db_name":"MESH","db_id":"D001480"}]},{"id":"15726","type":"Chemical","text":["risperidone"],"offsets":[[61,72]],"normalized":[{"db_name":"MESH","db_id":"D018967"}]},{"id":"15727","type":"Disease","text":["Rabbit syndrome"],"offsets":[[74,89]],"normalized":[{"db_name":"MESH","db_id":"D001480"}]},{"id":"15728","type":"Disease","text":["RS"],"offsets":[[91,93]],"normalized":[{"db_name":"MESH","db_id":"D001480"}]},{"id":"15729","type":"Disease","text":["withdrawal-emergent RS"],"offsets":[[202,224]],"normalized":[{"db_name":"MESH","db_id":"D013375"},{"db_name":"MESH","db_id":"D001480"}]},{"id":"15730","type":"Disease","text":["withdrawal","RS"],"offsets":[[202,212],[222,224]],"normalized":[{"db_name":"MESH","db_id":"D013375"}]},{"id":"15731","type":"Disease","text":["emergent RS"],"offsets":[[213,224]],"normalized":[{"db_name":"MESH","db_id":"D001480"}]},{"id":"15732","type":"Disease","text":["RS"],"offsets":[[295,297]],"normalized":[{"db_name":"MESH","db_id":"D001480"}]},{"id":"15733","type":"Chemical","text":["risperidone"],"offsets":[[323,334]],"normalized":[{"db_name":"MESH","db_id":"D018967"}]},{"id":"15734","type":"Chemical","text":["trihexyphenidyl"],"offsets":[[378,393]],"normalized":[{"db_name":"MESH","db_id":"D014282"}]},{"id":"15735","type":"Disease","text":["withdrawal-emergent RS"],"offsets":[[447,469]],"normalized":[{"db_name":"MESH","db_id":"D013375"},{"db_name":"MESH","db_id":"D001480"}]},{"id":"15736","type":"Disease","text":["withdrawal","RS"],"offsets":[[447,457],[467,469]],"normalized":[{"db_name":"MESH","db_id":"D013375"}]},{"id":"15737","type":"Disease","text":["emergent 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{"id":"15791","document_id":"3173179","passages":[{"id":"15792","type":"title","text":["Verapamil withdrawal as a possible cause of myocardial infarction in a hypertensive woman with a normal coronary angiogram."],"offsets":[[0,123]]},{"id":"15793","type":"abstract","text":["Verapamil is an effective and relatively-safe antihypertensive drug. Serious adverse effects are uncommon and mainly have been related to the depression of cardiac contractility and conduction, especially when the drug is combined with beta-blocking agents. We report a case in which myocardial infarction coincided with the introduction of captopril and the withdrawal of verapamil in a previously asymptomatic woman with severe hypertension. Possible mechanisms that involve a verapamil-related increase in platelet and\/or vascular alpha 2-adrenoreceptor affinity for catecholamines are discussed."],"offsets":[[124,723]]}],"entities":[{"id":"15794","type":"Chemical","text":["Verapamil"],"offsets":[[0,9]],"normalized":[{"db_name":"MESH","db_id":"D014700"}]},{"id":"15795","type":"Disease","text":["myocardial infarction"],"offsets":[[44,65]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"15796","type":"Disease","text":["hypertensive"],"offsets":[[71,83]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"15797","type":"Chemical","text":["Verapamil"],"offsets":[[124,133]],"normalized":[{"db_name":"MESH","db_id":"D014700"}]},{"id":"15798","type":"Disease","text":["depression"],"offsets":[[266,276]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"15799","type":"Disease","text":["myocardial infarction"],"offsets":[[408,429]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"15800","type":"Chemical","text":["captopril"],"offsets":[[465,474]],"normalized":[{"db_name":"MESH","db_id":"D002216"}]},{"id":"15801","type":"Chemical","text":["verapamil"],"offsets":[[497,506]],"normalized":[{"db_name":"MESH","db_id":"D014700"}]},{"id":"15802","type":"Disease","text":["hypertension"],"offsets":[[554,566]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"15803","type":"Chemical","text":["verapamil"],"offsets":[[603,612]],"normalized":[{"db_name":"MESH","db_id":"D014700"}]},{"id":"15804","type":"Chemical","text":["catecholamines"],"offsets":[[694,708]],"normalized":[{"db_name":"MESH","db_id":"D002395"}]}],"events":[],"coreferences":[],"relations":[{"id":"15805","type":"CID","arg1_id":"15794","arg2_id":"15795","normalized":[]},{"id":"15806","type":"CID","arg1_id":"15794","arg2_id":"15799","normalized":[]},{"id":"15807","type":"CID","arg1_id":"15797","arg2_id":"15795","normalized":[]},{"id":"15808","type":"CID","arg1_id":"15797","arg2_id":"15799","normalized":[]},{"id":"15809","type":"CID","arg1_id":"15801","arg2_id":"15795","normalized":[]},{"id":"15810","type":"CID","arg1_id":"15801","arg2_id":"15799","normalized":[]},{"id":"15811","type":"CID","arg1_id":"15803","arg2_id":"15795","normalized":[]},{"id":"15812","type":"CID","arg1_id":"15803","arg2_id":"15799","normalized":[]}]}
{"id":"15813","document_id":"3856631","passages":[{"id":"15814","type":"title","text":["Remission induction of meningeal leukemia with high-dose intravenous methotrexate."],"offsets":[[0,82]]},{"id":"15815","type":"abstract","text":["Twenty children with acute lymphoblastic leukemia who developed meningeal disease were treated with a high-dose intravenous methotrexate regimen that was designed to achieve and maintain CSF methotrexate concentrations of 10(-5) mol\/L without the need for concomitant intrathecal dosing. The methotrexate was administered as a loading dose of 6,000 mg\/m2 for a period of one hour followed by an infusion of 1,200 mg\/m2\/h for 23 hours. Leucovorin rescue was initiated 12 hours after the end of the infusion with a loading dose of 200 mg\/m2 followed by 12 mg\/m2 every three hours for six doses and then every six hours until the plasma methotrexate level decreased to less than 1 X 10(-7) mol\/L. The mean steady-state plasma and CSF methotrexate concentrations achieved were 1.1 X 10(-3) mol\/L and 3.6 X 10(-5) mol\/L, respectively. All 20 patients responded to this regimen, 16\/20 (80%) achieved a complete remission, and 20% obtained a partial remission. The most common toxicities encountered were transient serum transaminase and bilirubin elevations, neutropenia, and mucositis. One patient had focal seizures and transient hemiparesis but recovered completely. High-dose intravenous methotrexate is an effective treatment for the induction of remission after meningeal relapse in acute lymphoblastic leukemia."],"offsets":[[83,1395]]}],"entities":[{"id":"15816","type":"Disease","text":["meningeal leukemia"],"offsets":[[23,41]],"normalized":[{"db_name":"MESH","db_id":"D008577"}]},{"id":"15817","type":"Chemical","text":["methotrexate"],"offsets":[[69,81]],"normalized":[{"db_name":"MESH","db_id":"D008727"}]},{"id":"15818","type":"Disease","text":["acute lymphoblastic leukemia"],"offsets":[[104,132]],"normalized":[{"db_name":"MESH","db_id":"D054198"}]},{"id":"15819","type":"Disease","text":["meningeal disease"],"offsets":[[147,164]],"normalized":[{"db_name":"MESH","db_id":"D002493"}]},{"id":"15820","type":"Chemical","text":["methotrexate"],"offsets":[[207,219]],"normalized":[{"db_name":"MESH","db_id":"D008727"}]},{"id":"15821","type":"Chemical","text":["methotrexate"],"offsets":[[274,286]],"normalized":[{"db_name":"MESH","db_id":"D008727"}]},{"id":"15822","type":"Chemical","text":["methotrexate"],"offsets":[[375,387]],"normalized":[{"db_name":"MESH","db_id":"D008727"}]},{"id":"15823","type":"Chemical","text":["Leucovorin"],"offsets":[[518,528]],"normalized":[{"db_name":"MESH","db_id":"D002955"}]},{"id":"15824","type":"Chemical","text":["methotrexate"],"offsets":[[717,729]],"normalized":[{"db_name":"MESH","db_id":"D008727"}]},{"id":"15825","type":"Chemical","text":["methotrexate"],"offsets":[[814,826]],"normalized":[{"db_name":"MESH","db_id":"D008727"}]},{"id":"15826","type":"Disease","text":["toxicities"],"offsets":[[1053,1063]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"15827","type":"Chemical","text":["bilirubin"],"offsets":[[1114,1123]],"normalized":[{"db_name":"MESH","db_id":"D001663"}]},{"id":"15828","type":"Disease","text":["neutropenia"],"offsets":[[1136,1147]],"normalized":[{"db_name":"MESH","db_id":"D009503"}]},{"id":"15829","type":"Disease","text":["mucositis"],"offsets":[[1153,1162]],"normalized":[{"db_name":"MESH","db_id":"D052016"}]},{"id":"15830","type":"Disease","text":["seizures"],"offsets":[[1186,1194]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"15831","type":"Disease","text":["transient hemiparesis"],"offsets":[[1199,1220]],"normalized":[{"db_name":"MESH","db_id":"D010291"}]},{"id":"15832","type":"Chemical","text":["methotrexate"],"offsets":[[1269,1281]],"normalized":[{"db_name":"MESH","db_id":"D008727"}]},{"id":"15833","type":"Disease","text":["acute lymphoblastic leukemia"],"offsets":[[1366,1394]],"normalized":[{"db_name":"MESH","db_id":"D054198"}]}],"events":[],"coreferences":[],"relations":[{"id":"15834","type":"CID","arg1_id":"15817","arg2_id":"15831","normalized":[]},{"id":"15835","type":"CID","arg1_id":"15820","arg2_id":"15831","normalized":[]},{"id":"15836","type":"CID","arg1_id":"15821","arg2_id":"15831","normalized":[]},{"id":"15837","type":"CID","arg1_id":"15822","arg2_id":"15831","normalized":[]},{"id":"15838","type":"CID","arg1_id":"15824","arg2_id":"15831","normalized":[]},{"id":"15839","type":"CID","arg1_id":"15825","arg2_id":"15831","normalized":[]},{"id":"15840","type":"CID","arg1_id":"15832","arg2_id":"15831","normalized":[]},{"id":"15841","type":"CID","arg1_id":"15817","arg2_id":"15828","normalized":[]},{"id":"15842","type":"CID","arg1_id":"15820","arg2_id":"15828","normalized":[]},{"id":"15843","type":"CID","arg1_id":"15821","arg2_id":"15828","normalized":[]},{"id":"15844","type":"CID","arg1_id":"15822","arg2_id":"15828","normalized":[]},{"id":"15845","type":"CID","arg1_id":"15824","arg2_id":"15828","normalized":[]},{"id":"15846","type":"CID","arg1_id":"15825","arg2_id":"15828","normalized":[]},{"id":"15847","type":"CID","arg1_id":"15832","arg2_id":"15828","normalized":[]},{"id":"15848","type":"CID","arg1_id":"15817","arg2_id":"15830","normalized":[]},{"id":"15849","type":"CID","arg1_id":"15820","arg2_id":"15830","normalized":[]},{"id":"15850","type":"CID","arg1_id":"15821","arg2_id":"15830","normalized":[]},{"id":"15851","type":"CID","arg1_id":"15822","arg2_id":"15830","normalized":[]},{"id":"15852","type":"CID","arg1_id":"15824","arg2_id":"15830","normalized":[]},{"id":"15853","type":"CID","arg1_id":"15825","arg2_id":"15830","normalized":[]},{"id":"15854","type":"CID","arg1_id":"15832","arg2_id":"15830","normalized":[]},{"id":"15855","type":"CID","arg1_id":"15817","arg2_id":"15829","normalized":[]},{"id":"15856","type":"CID","arg1_id":"15820","arg2_id":"15829","normalized":[]},{"id":"15857","type":"CID","arg1_id":"15821","arg2_id":"15829","normalized":[]},{"id":"15858","type":"CID","arg1_id":"15822","arg2_id":"15829","normalized":[]},{"id":"15859","type":"CID","arg1_id":"15824","arg2_id":"15829","normalized":[]},{"id":"15860","type":"CID","arg1_id":"15825","arg2_id":"15829","normalized":[]},{"id":"15861","type":"CID","arg1_id":"15832","arg2_id":"15829","normalized":[]}]}
{"id":"15862","document_id":"2522601","passages":[{"id":"15863","type":"title","text":["Hypersensitivity to carbamazepine presenting with a leukemoid reaction, eosinophilia, erythroderma, and renal failure."],"offsets":[[0,118]]},{"id":"15864","type":"abstract","text":["We report a patient in whom hypersensitivity to carbamazepine presented with generalized erythroderma, a severe leukemoid reaction, eosinophilia, hyponatremia, and renal failure. This is the first report of such an unusual reaction to carbamazepine."],"offsets":[[119,368]]}],"entities":[{"id":"15865","type":"Disease","text":["Hypersensitivity"],"offsets":[[0,16]],"normalized":[{"db_name":"MESH","db_id":"D004342"}]},{"id":"15866","type":"Chemical","text":["carbamazepine"],"offsets":[[20,33]],"normalized":[{"db_name":"MESH","db_id":"D002220"}]},{"id":"15867","type":"Disease","text":["leukemoid reaction"],"offsets":[[52,70]],"normalized":[{"db_name":"MESH","db_id":"D007955"}]},{"id":"15868","type":"Disease","text":["eosinophilia"],"offsets":[[72,84]],"normalized":[{"db_name":"MESH","db_id":"D004802"}]},{"id":"15869","type":"Disease","text":["erythroderma"],"offsets":[[86,98]],"normalized":[{"db_name":"MESH","db_id":"D003873"}]},{"id":"15870","type":"Disease","text":["renal failure"],"offsets":[[104,117]],"normalized":[{"db_name":"MESH","db_id":"D051437"}]},{"id":"15871","type":"Disease","text":["hypersensitivity"],"offsets":[[147,163]],"normalized":[{"db_name":"MESH","db_id":"D004342"}]},{"id":"15872","type":"Chemical","text":["carbamazepine"],"offsets":[[167,180]],"normalized":[{"db_name":"MESH","db_id":"D002220"}]},{"id":"15873","type":"Disease","text":["erythroderma"],"offsets":[[208,220]],"normalized":[{"db_name":"MESH","db_id":"D003873"}]},{"id":"15874","type":"Disease","text":["leukemoid reaction"],"offsets":[[231,249]],"normalized":[{"db_name":"MESH","db_id":"D007955"}]},{"id":"15875","type":"Disease","text":["eosinophilia"],"offsets":[[251,263]],"normalized":[{"db_name":"MESH","db_id":"D004802"}]},{"id":"15876","type":"Disease","text":["hyponatremia"],"offsets":[[265,277]],"normalized":[{"db_name":"MESH","db_id":"D007010"}]},{"id":"15877","type":"Disease","text":["renal failure"],"offsets":[[283,296]],"normalized":[{"db_name":"MESH","db_id":"D051437"}]},{"id":"15878","type":"Chemical","text":["carbamazepine"],"offsets":[[354,367]],"normalized":[{"db_name":"MESH","db_id":"D002220"}]}],"events":[],"coreferences":[],"relations":[{"id":"15879","type":"CID","arg1_id":"15866","arg2_id":"15870","normalized":[]},{"id":"15880","type":"CID","arg1_id":"15866","arg2_id":"15877","normalized":[]},{"id":"15881","type":"CID","arg1_id":"15872","arg2_id":"15870","normalized":[]},{"id":"15882","type":"CID","arg1_id":"15872","arg2_id":"15877","normalized":[]},{"id":"15883","type":"CID","arg1_id":"15878","arg2_id":"15870","normalized":[]},{"id":"15884","type":"CID","arg1_id":"15878","arg2_id":"15877","normalized":[]},{"id":"15885","type":"CID","arg1_id":"15866","arg2_id":"15869","normalized":[]},{"id":"15886","type":"CID","arg1_id":"15866","arg2_id":"15873","normalized":[]},{"id":"15887","type":"CID","arg1_id":"15872","arg2_id":"15869","normalized":[]},{"id":"15888","type":"CID","arg1_id":"15872","arg2_id":"15873","normalized":[]},{"id":"15889","type":"CID","arg1_id":"15878","arg2_id":"15869","normalized":[]},{"id":"15890","type":"CID","arg1_id":"15878","arg2_id":"15873","normalized":[]},{"id":"15891","type":"CID","arg1_id":"15866","arg2_id":"15867","normalized":[]},{"id":"15892","type":"CID","arg1_id":"15866","arg2_id":"15874","normalized":[]},{"id":"15893","type":"CID","arg1_id":"15872","arg2_id":"15867","normalized":[]},{"id":"15894","type":"CID","arg1_id":"15872","arg2_id":"15874","normalized":[]},{"id":"15895","type":"CID","arg1_id":"15878","arg2_id":"15867","normalized":[]},{"id":"15896","type":"CID","arg1_id":"15878","arg2_id":"15874","normalized":[]},{"id":"15897","type":"CID","arg1_id":"15866","arg2_id":"15865","normalized":[]},{"id":"15898","type":"CID","arg1_id":"15866","arg2_id":"15871","normalized":[]},{"id":"15899","type":"CID","arg1_id":"15872","arg2_id":"15865","normalized":[]},{"id":"15900","type":"CID","arg1_id":"15872","arg2_id":"15871","normalized":[]},{"id":"15901","type":"CID","arg1_id":"15878","arg2_id":"15865","normalized":[]},{"id":"15902","type":"CID","arg1_id":"15878","arg2_id":"15871","normalized":[]},{"id":"15903","type":"CID","arg1_id":"15866","arg2_id":"15876","normalized":[]},{"id":"15904","type":"CID","arg1_id":"15872","arg2_id":"15876","normalized":[]},{"id":"15905","type":"CID","arg1_id":"15878","arg2_id":"15876","normalized":[]}]}
{"id":"15906","document_id":"8741744","passages":[{"id":"15907","type":"title","text":["The interpeduncular nucleus regulates nicotine's effects on free-field activity."],"offsets":[[0,80]]},{"id":"15908","type":"abstract","text":["Partial lesions were made with kainic acid in the interpeduncular nucleus of the ventral midbrain of the rat. Compared with sham-operated controls, lesions significantly (p < 0.25) blunted the early (<60 min) free-field locomotor hypoactivity caused by nicotine (0.5 mg kg(-1), i.m.), enhanced the later (60-120 min) nicotine-induced hyperactivity, and raised spontaneous nocturnal activity. Lesions reduced the extent of immunohistological staining for choline acetyltransferase in the interpeduncular nucleus (p <0.025), but not for tyrosine hydroxylase in the surrounding catecholaminergic A10 region. We conclude that the interpeduncular nucleus mediates nicotinic depression of locomotor activity and dampens nicotinic arousal mechanisms located elsewhere in the brain."],"offsets":[[81,855]]}],"entities":[{"id":"15909","type":"Chemical","text":["nicotine"],"offsets":[[38,46]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"15910","type":"Chemical","text":["kainic acid"],"offsets":[[112,123]],"normalized":[{"db_name":"MESH","db_id":"D007608"}]},{"id":"15911","type":"Disease","text":["locomotor hypoactivity"],"offsets":[[301,323]],"normalized":[{"db_name":"MESH","db_id":"D009069"}]},{"id":"15912","type":"Chemical","text":["nicotine"],"offsets":[[334,342]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"15913","type":"Chemical","text":["nicotine"],"offsets":[[398,406]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"15914","type":"Disease","text":["hyperactivity"],"offsets":[[415,428]],"normalized":[{"db_name":"MESH","db_id":"D006948"}]},{"id":"15915","type":"Chemical","text":["choline"],"offsets":[[535,542]],"normalized":[{"db_name":"MESH","db_id":"D002794"}]},{"id":"15916","type":"Chemical","text":["tyrosine"],"offsets":[[616,624]],"normalized":[{"db_name":"MESH","db_id":"D014443"}]},{"id":"15917","type":"Disease","text":["depression"],"offsets":[[750,760]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]}],"events":[],"coreferences":[],"relations":[{"id":"15918","type":"CID","arg1_id":"15909","arg2_id":"15914","normalized":[]},{"id":"15919","type":"CID","arg1_id":"15912","arg2_id":"15914","normalized":[]},{"id":"15920","type":"CID","arg1_id":"15913","arg2_id":"15914","normalized":[]}]}
{"id":"15921","document_id":"17491223","passages":[{"id":"15922","type":"title","text":["Assessment of a new non-invasive index of cardiac performance for detection of dobutamine-induced myocardial ischemia."],"offsets":[[0,118]]},{"id":"15923","type":"abstract","text":["BACKGROUND: Electrocardiography has a very low sensitivity in detecting dobutamine-induced myocardial ischemia. OBJECTIVES: To assess the added diagnostic value of a new cardiac performance index (dP\/dtejc) measurement, based on brachial artery flow changes, as compared to standard 12-lead ECG, for detecting dobutamine-induced myocardial ischemia, using Tc99m-Sestamibi single-photon emission computed tomography as the gold standard of comparison to assess the presence or absence of ischemia. METHODS: The study group comprised 40 patients undergoing Sestamibi-SPECT\/dobutamine stress test. Simultaneous measurements of ECG and brachial artery dP\/dtejc were performed at each dobutamine level. In 19 of the 40 patients perfusion defects compatible with ischemia were detected on SPECT. The increase in dP\/dtejc during infusion of dobutamine in this group was severely impaired as compared to the non-ischemic group. dP\/dtejc outcome was combined with the ECG results, giving an ECG-enhanced value, and compared to ECG alone. RESULTS: The sensitivity improved dramatically from 16% to 79%, positive predictive value increased from 60% to 68% and negative predictive value from 54% to 78%, and specificity decreased from 90% to 67%. CONCLUSIONS: If ECG alone is used for specificity, the combination with dP\/dtejc improved the sensitivity of the test and could be a cost-savings alternative to cardiac imaging or perfusion studies to detect myocardial ischemia, especially in patients unable to exercise."],"offsets":[[119,1625]]}],"entities":[{"id":"15924","type":"Chemical","text":["dobutamine"],"offsets":[[79,89]],"normalized":[{"db_name":"MESH","db_id":"D004280"}]},{"id":"15925","type":"Disease","text":["myocardial ischemia"],"offsets":[[98,117]],"normalized":[{"db_name":"MESH","db_id":"D017202"}]},{"id":"15926","type":"Chemical","text":["dobutamine"],"offsets":[[191,201]],"normalized":[{"db_name":"MESH","db_id":"D004280"}]},{"id":"15927","type":"Disease","text":["myocardial ischemia"],"offsets":[[210,229]],"normalized":[{"db_name":"MESH","db_id":"D017202"}]},{"id":"15928","type":"Chemical","text":["dobutamine"],"offsets":[[429,439]],"normalized":[{"db_name":"MESH","db_id":"D004280"}]},{"id":"15929","type":"Disease","text":["myocardial ischemia"],"offsets":[[448,467]],"normalized":[{"db_name":"MESH","db_id":"D017202"}]},{"id":"15930","type":"Chemical","text":["Tc99m-Sestamibi"],"offsets":[[475,490]],"normalized":[{"db_name":"MESH","db_id":"D017256"}]},{"id":"15931","type":"Disease","text":["ischemia"],"offsets":[[606,614]],"normalized":[{"db_name":"MESH","db_id":"D007511"}]},{"id":"15932","type":"Chemical","text":["Sestamibi"],"offsets":[[674,683]],"normalized":[{"db_name":"MESH","db_id":"D017256"}]},{"id":"15933","type":"Chemical","text":["dobutamine"],"offsets":[[690,700]],"normalized":[{"db_name":"MESH","db_id":"D004280"}]},{"id":"15934","type":"Chemical","text":["dobutamine"],"offsets":[[799,809]],"normalized":[{"db_name":"MESH","db_id":"D004280"}]},{"id":"15935","type":"Disease","text":["ischemia"],"offsets":[[876,884]],"normalized":[{"db_name":"MESH","db_id":"D007511"}]},{"id":"15936","type":"Chemical","text":["dobutamine"],"offsets":[[953,963]],"normalized":[{"db_name":"MESH","db_id":"D004280"}]},{"id":"15937","type":"Disease","text":["myocardial ischemia"],"offsets":[[1562,1581]],"normalized":[{"db_name":"MESH","db_id":"D017202"}]}],"events":[],"coreferences":[],"relations":[{"id":"15938","type":"CID","arg1_id":"15924","arg2_id":"15925","normalized":[]},{"id":"15939","type":"CID","arg1_id":"15924","arg2_id":"15927","normalized":[]},{"id":"15940","type":"CID","arg1_id":"15924","arg2_id":"15929","normalized":[]},{"id":"15941","type":"CID","arg1_id":"15924","arg2_id":"15937","normalized":[]},{"id":"15942","type":"CID","arg1_id":"15926","arg2_id":"15925","normalized":[]},{"id":"15943","type":"CID","arg1_id":"15926","arg2_id":"15927","normalized":[]},{"id":"15944","type":"CID","arg1_id":"15926","arg2_id":"15929","normalized":[]},{"id":"15945","type":"CID","arg1_id":"15926","arg2_id":"15937","normalized":[]},{"id":"15946","type":"CID","arg1_id":"15928","arg2_id":"15925","normalized":[]},{"id":"15947","type":"CID","arg1_id":"15928","arg2_id":"15927","normalized":[]},{"id":"15948","type":"CID","arg1_id":"15928","arg2_id":"15929","normalized":[]},{"id":"15949","type":"CID","arg1_id":"15928","arg2_id":"15937","normalized":[]},{"id":"15950","type":"CID","arg1_id":"15933","arg2_id":"15925","normalized":[]},{"id":"15951","type":"CID","arg1_id":"15933","arg2_id":"15927","normalized":[]},{"id":"15952","type":"CID","arg1_id":"15933","arg2_id":"15929","normalized":[]},{"id":"15953","type":"CID","arg1_id":"15933","arg2_id":"15937","normalized":[]},{"id":"15954","type":"CID","arg1_id":"15934","arg2_id":"15925","normalized":[]},{"id":"15955","type":"CID","arg1_id":"15934","arg2_id":"15927","normalized":[]},{"id":"15956","type":"CID","arg1_id":"15934","arg2_id":"15929","normalized":[]},{"id":"15957","type":"CID","arg1_id":"15934","arg2_id":"15937","normalized":[]},{"id":"15958","type":"CID","arg1_id":"15936","arg2_id":"15925","normalized":[]},{"id":"15959","type":"CID","arg1_id":"15936","arg2_id":"15927","normalized":[]},{"id":"15960","type":"CID","arg1_id":"15936","arg2_id":"15929","normalized":[]},{"id":"15961","type":"CID","arg1_id":"15936","arg2_id":"15937","normalized":[]}]}
{"id":"15962","document_id":"18004067","passages":[{"id":"15963","type":"title","text":["Acute liver failure in two patients with regular alcohol consumption ingesting paracetamol at therapeutic dosage."],"offsets":[[0,113]]},{"id":"15964","type":"abstract","text":["BACKGROUND: The possible role of alcohol in the development of hepatotoxicity associated with therapeutic doses of paracetamol (acetaminophen) is currently debated. CASE REPORT: We describe 2 patients who were regular consumers of alcohol and who developed liver failure within 3-5 days after hospitalization and stopping alcohol consumption while being treated with 4 g paracetamol\/day. A paracetamol serum level obtained in one of these patients was not in the toxic range. Possible risk factors for the development of hepatotoxicity in patients treated with therapeutic doses of paracetamol are discussed. CONCLUSION: In patients with risk factors, e.g. regular consumption of alcohol, liver failure is possible when therapeutic doses are ingested. We propose that the paracetamol dose should not exceed 2 g\/day in such patients and that their liver function should be monitored closely while being treated with paracetamol."],"offsets":[[114,1041]]}],"entities":[{"id":"15965","type":"Disease","text":["Acute liver failure"],"offsets":[[0,19]],"normalized":[{"db_name":"MESH","db_id":"D017114"}]},{"id":"15966","type":"Chemical","text":["alcohol"],"offsets":[[49,56]],"normalized":[{"db_name":"MESH","db_id":"D000431"}]},{"id":"15967","type":"Chemical","text":["paracetamol"],"offsets":[[79,90]],"normalized":[{"db_name":"MESH","db_id":"D000082"}]},{"id":"15968","type":"Chemical","text":["alcohol"],"offsets":[[147,154]],"normalized":[{"db_name":"MESH","db_id":"D000431"}]},{"id":"15969","type":"Disease","text":["hepatotoxicity"],"offsets":[[177,191]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"15970","type":"Chemical","text":["paracetamol"],"offsets":[[229,240]],"normalized":[{"db_name":"MESH","db_id":"D000082"}]},{"id":"15971","type":"Chemical","text":["acetaminophen"],"offsets":[[242,255]],"normalized":[{"db_name":"MESH","db_id":"D000082"}]},{"id":"15972","type":"Chemical","text":["alcohol"],"offsets":[[345,352]],"normalized":[{"db_name":"MESH","db_id":"D000431"}]},{"id":"15973","type":"Disease","text":["liver failure"],"offsets":[[371,384]],"normalized":[{"db_name":"MESH","db_id":"D017093"}]},{"id":"15974","type":"Chemical","text":["alcohol"],"offsets":[[436,443]],"normalized":[{"db_name":"MESH","db_id":"D000431"}]},{"id":"15975","type":"Chemical","text":["paracetamol"],"offsets":[[485,496]],"normalized":[{"db_name":"MESH","db_id":"D000082"}]},{"id":"15976","type":"Chemical","text":["paracetamol"],"offsets":[[504,515]],"normalized":[{"db_name":"MESH","db_id":"D000082"}]},{"id":"15977","type":"Disease","text":["hepatotoxicity"],"offsets":[[635,649]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"15978","type":"Chemical","text":["paracetamol"],"offsets":[[696,707]],"normalized":[{"db_name":"MESH","db_id":"D000082"}]},{"id":"15979","type":"Chemical","text":["alcohol"],"offsets":[[794,801]],"normalized":[{"db_name":"MESH","db_id":"D000431"}]},{"id":"15980","type":"Disease","text":["liver 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{"id":"16015","document_id":"12443032","passages":[{"id":"16016","type":"title","text":["Cocaine related chest pain: are we seeing the tip of an iceberg?"],"offsets":[[0,64]]},{"id":"16017","type":"abstract","text":["The recreational use of cocaine is on the increase. The emergency nurse ought to be familiar with some of the cardiovascular consequences of cocaine use. In particular, the tendency of cocaine to produce chest pain ought to be in the mind of the emergency nurse when faced with a young victim of chest pain who is otherwise at low risk. The mechanism of chest pain related to cocaine use is discussed and treatment dilemmas are discussed. Finally, moral issues relating to the testing of potential cocaine users will be addressed."],"offsets":[[65,595]]}],"entities":[{"id":"16018","type":"Chemical","text":["Cocaine"],"offsets":[[0,7]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"16019","type":"Disease","text":["chest pain"],"offsets":[[16,26]],"normalized":[{"db_name":"MESH","db_id":"D002637"}]},{"id":"16020","type":"Chemical","text":["cocaine"],"offsets":[[89,96]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"16021","type":"Chemical","text":["cocaine"],"offsets":[[206,213]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"16022","type":"Chemical","text":["cocaine"],"offsets":[[250,257]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"16023","type":"Disease","text":["chest pain"],"offsets":[[269,279]],"normalized":[{"db_name":"MESH","db_id":"D002637"}]},{"id":"16024","type":"Disease","text":["chest pain"],"offsets":[[361,371]],"normalized":[{"db_name":"MESH","db_id":"D002637"}]},{"id":"16025","type":"Disease","text":["chest pain"],"offsets":[[419,429]],"normalized":[{"db_name":"MESH","db_id":"D002637"}]},{"id":"16026","type":"Chemical","text":["cocaine"],"offsets":[[441,448]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"16027","type":"Chemical","text":["cocaine"],"offsets":[[563,570]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]}],"events":[],"coreferences":[],"relations":[{"id":"16028","type":"CID","arg1_id":"16018","arg2_id":"16019","normalized":[]},{"id":"16029","type":"CID","arg1_id":"16018","arg2_id":"16023","normalized":[]},{"id":"16030","type":"CID","arg1_id":"16018","arg2_id":"16024","normalized":[]},{"id":"16031","type":"CID","arg1_id":"16018","arg2_id":"16025","normalized":[]},{"id":"16032","type":"CID","arg1_id":"16020","arg2_id":"16019","normalized":[]},{"id":"16033","type":"CID","arg1_id":"16020","arg2_id":"16023","normalized":[]},{"id":"16034","type":"CID","arg1_id":"16020","arg2_id":"16024","normalized":[]},{"id":"16035","type":"CID","arg1_id":"16020","arg2_id":"16025","normalized":[]},{"id":"16036","type":"CID","arg1_id":"16021","arg2_id":"16019","normalized":[]},{"id":"16037","type":"CID","arg1_id":"16021","arg2_id":"16023","normalized":[]},{"id":"16038","type":"CID","arg1_id":"16021","arg2_id":"16024","normalized":[]},{"id":"16039","type":"CID","arg1_id":"16021","arg2_id":"16025","normalized":[]},{"id":"16040","type":"CID","arg1_id":"16022","arg2_id":"16019","normalized":[]},{"id":"16041","type":"CID","arg1_id":"16022","arg2_id":"16023","normalized":[]},{"id":"16042","type":"CID","arg1_id":"16022","arg2_id":"16024","normalized":[]},{"id":"16043","type":"CID","arg1_id":"16022","arg2_id":"16025","normalized":[]},{"id":"16044","type":"CID","arg1_id":"16026","arg2_id":"16019","normalized":[]},{"id":"16045","type":"CID","arg1_id":"16026","arg2_id":"16023","normalized":[]},{"id":"16046","type":"CID","arg1_id":"16026","arg2_id":"16024","normalized":[]},{"id":"16047","type":"CID","arg1_id":"16026","arg2_id":"16025","normalized":[]},{"id":"16048","type":"CID","arg1_id":"16027","arg2_id":"16019","normalized":[]},{"id":"16049","type":"CID","arg1_id":"16027","arg2_id":"16023","normalized":[]},{"id":"16050","type":"CID","arg1_id":"16027","arg2_id":"16024","normalized":[]},{"id":"16051","type":"CID","arg1_id":"16027","arg2_id":"16025","normalized":[]}]}
{"id":"16052","document_id":"17615423","passages":[{"id":"16053","type":"title","text":["Severe rhabdomyolysis and acute renal failure secondary to concomitant use of simvastatin, amiodarone, and atazanavir."],"offsets":[[0,118]]},{"id":"16054","type":"abstract","text":["OBJECTIVE: To report a case of a severe interaction between simvastatin, amiodarone, and atazanavir resulting in rhabdomyolysis and acute renal failure. BACKGROUND: A 72-year-old white man with underlying human immunodeficiency virus, atrial fibrillation, coronary artery disease, and hyperlipidemia presented with generalized pain, fatigue, and dark orange urine for 3 days. The patient was taking 80 mg simvastatin at bedtime (initiated 27 days earlier); amiodarone at a dose of 400 mg daily for 7 days, then 200 mg daily (initiated 19 days earlier); and 400 mg atazanavir daily (initiated at least 2 years previously). Laboratory evaluation revealed 66,680 U\/L creatine kinase, 93 mg\/dL blood urea nitrogen, 4.6 mg\/dL creatinine, 1579 U\/L aspartate aminotransferase, and 738 U\/L alanine aminotransferase. Simvastatin, amiodarone, and the patient's human immunodeficiency virus medications were all temporarily discontinued and the patient was given forced alkaline diuresis and started on dialysis. Nine days later the patient's creatine kinase had dropped to 1695 U\/L and creatinine was 3.3 mg\/dL. The patient was discharged and continued outpatient dialysis for 1 month until his renal function recovered. DISCUSSION: The risk of rhabdomyolysis is increased in the presence of concomitant drugs that inhibit simvastatin metabolism. Simvastatin is metabolized by CYP3A4. Amiodarone and atazanavir are recognized CYP3A4 inhibitors. CONCLUSIONS: Pharmacokinetic differences in statins are an important consideration for assessing the risk of potential drug interactions. In patients requiring the concurrent use of statins and CYP3A4 inhibitors, pravastatin, fluvastatin, and rosuvastatin carry the lowest risk of drug interactions; atorvastatin carries moderate risk, whereas simvastatin and lovastatin have the highest risk and should be avoided in patients taking concomitant CYP3A4 inhibitors."],"offsets":[[119,2018]]}],"entities":[{"id":"16055","type":"Disease","text":["rhabdomyolysis"],"offsets":[[7,21]],"normalized":[{"db_name":"MESH","db_id":"D012206"}]},{"id":"16056","type":"Disease","text":["acute renal 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{"id":"16187","document_id":"8558192","passages":[{"id":"16188","type":"title","text":["Phase II trial of vinorelbine in metastatic squamous cell esophageal carcinoma. European Organization for Research and Treatment of Cancer Gastrointestinal Treat Cancer Cooperative Group."],"offsets":[[0,187]]},{"id":"16189","type":"abstract","text":["PURPOSE: To evaluate the response rate and toxic effects of vinorelbine (VNB) administered as a single agent in metastatic squamous cell esophageal carcinoma. PATIENTS AND METHODS: Forty-six eligible patients with measurable lesions were included and were stratified according to previous chemotherapy. Thirty patients without prior chemotherapy and 16 pretreated with cisplatin-based chemotherapy were assessable for toxicity and response. VNB was administered weekly as a 25-mg\/m2 short intravenous (i.v.) infusion. RESULTS: Six of 30 patients (20%) without prior chemotherapy achieved a partial response (PR) (95% confidence interval [CI], 8% to 39%). The median duration of response was 21 weeks (range, 17 to 28). One of 16 patients (6%) with prior chemotherapy had a complete response (CR) of 31 weeks' duration (95% CI, 0% to 30%). The overall response rate (World Health Organization [WHO] criteria) was 15% (CR, 2%; PR 13%; 95% CI, 6% to 29%). The median dose-intensity (DI) was 20 mg\/m2\/wk. VNB was well tolerated and zero instances of WHO grade 4 nonhematologic toxicity occurred. At least one episode of grade 3 or 4 granulocytopenia was seen in 59% of patients. A grade 2 or 3 infection occurred in 16% of patients, but no toxic deaths occurred. Other side effects were rare, and peripheral neurotoxicity has been minor (26% grade 1). CONCLUSION: These data indicate that VNB is an active agent in metastatic esophageal squamous cell carcinoma. Given its excellent tolerance profile and low toxicity, further evaluation of VNB in combination therapy is warranted."],"offsets":[[188,1764]]}],"entities":[{"id":"16190","type":"Chemical","text":["vinorelbine"],"offsets":[[18,29]],"normalized":[{"db_name":"MESH","db_id":"C030852"}]},{"id":"16191","type":"Disease","text":["squamous cell esophageal carcinoma"],"offsets":[[44,78]],"normalized":[{"db_name":"MESH","db_id":"C562729"}]},{"id":"16192","type":"Disease","text":["Cancer"],"offsets":[[132,138]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"16193","type":"Disease","text":["Cancer"],"offsets":[[162,168]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"16194","type":"Chemical","text":["vinorelbine"],"offsets":[[248,259]],"normalized":[{"db_name":"MESH","db_id":"C030852"}]},{"id":"16195","type":"Chemical","text":["VNB"],"offsets":[[261,264]],"normalized":[{"db_name":"MESH","db_id":"C030852"}]},{"id":"16196","type":"Disease","text":["squamous cell esophageal carcinoma"],"offsets":[[311,345]],"normalized":[{"db_name":"MESH","db_id":"C562729"}]},{"id":"16197","type":"Chemical","text":["cisplatin"],"offsets":[[557,566]],"normalized":[{"db_name":"MESH","db_id":"D002945"}]},{"id":"16198","type":"Disease","text":["toxicity"],"offsets":[[606,614]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"16199","type":"Chemical","text":["VNB"],"offsets":[[629,632]],"normalized":[{"db_name":"MESH","db_id":"C030852"}]},{"id":"16200","type":"Chemical","text":["VNB"],"offsets":[[1189,1192]],"normalized":[{"db_name":"MESH","db_id":"C030852"}]},{"id":"16201","type":"Disease","text":["toxicity"],"offsets":[[1261,1269]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"16202","type":"Disease","text":["granulocytopenia"],"offsets":[[1317,1333]],"normalized":[{"db_name":"MESH","db_id":"D000380"}]},{"id":"16203","type":"Disease","text":["infection"],"offsets":[[1378,1387]],"normalized":[{"db_name":"MESH","db_id":"D007239"}]},{"id":"16204","type":"Disease","text":["deaths"],"offsets":[[1430,1436]],"normalized":[{"db_name":"MESH","db_id":"D003643"}]},{"id":"16205","type":"Disease","text":["peripheral neurotoxicity"],"offsets":[[1481,1505]],"normalized":[{"db_name":"MESH","db_id":"D010523"}]},{"id":"16206","type":"Chemical","text":["VNB"],"offsets":[[1573,1576]],"normalized":[{"db_name":"MESH","db_id":"C030852"}]},{"id":"16207","type":"Disease","text":["esophageal squamous cell carcinoma"],"offsets":[[1610,1644]],"normalized":[{"db_name":"MESH","db_id":"C562729"}]},{"id":"16208","type":"Disease","text":["toxicity"],"offsets":[[1692,1700]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"16209","type":"Chemical","text":["VNB"],"offsets":[[1724,1727]],"normalized":[{"db_name":"MESH","db_id":"C030852"}]}],"events":[],"coreferences":[],"relations":[{"id":"16210","type":"CID","arg1_id":"16190","arg2_id":"16202","normalized":[]},{"id":"16211","type":"CID","arg1_id":"16194","arg2_id":"16202","normalized":[]},{"id":"16212","type":"CID","arg1_id":"16195","arg2_id":"16202","normalized":[]},{"id":"16213","type":"CID","arg1_id":"16199","arg2_id":"16202","normalized":[]},{"id":"16214","type":"CID","arg1_id":"16200","arg2_id":"16202","normalized":[]},{"id":"16215","type":"CID","arg1_id":"16206","arg2_id":"16202","normalized":[]},{"id":"16216","type":"CID","arg1_id":"16209","arg2_id":"16202","normalized":[]},{"id":"16217","type":"CID","arg1_id":"16190","arg2_id":"16205","normalized":[]},{"id":"16218","type":"CID","arg1_id":"16194","arg2_id":"16205","normalized":[]},{"id":"16219","type":"CID","arg1_id":"16195","arg2_id":"16205","normalized":[]},{"id":"16220","type":"CID","arg1_id":"16199","arg2_id":"16205","normalized":[]},{"id":"16221","type":"CID","arg1_id":"16200","arg2_id":"16205","normalized":[]},{"id":"16222","type":"CID","arg1_id":"16206","arg2_id":"16205","normalized":[]},{"id":"16223","type":"CID","arg1_id":"16209","arg2_id":"16205","normalized":[]}]}
{"id":"16224","document_id":"11135224","passages":[{"id":"16225","type":"title","text":["Paclitaxel, cisplatin, and gemcitabine combination chemotherapy within a multidisciplinary therapeutic approach in metastatic nonsmall cell lung carcinoma."],"offsets":[[0,155]]},{"id":"16226","type":"abstract","text":["BACKGROUND: Cisplatin-based chemotherapy combinations improve quality of life and survival in advanced nonsmall cell lung carcinoma (NSCLC). The emergence of new active drugs might translate into more effective regimens for the treatment of this disease. METHODS: The objective of this study was to determine the feasibility, response rate, and toxicity of a paclitaxel, cisplatin, and gemcitabine combination to treat metastatic NSCLC. Thirty-five consecutive chemotherapy-naive patients with Stage IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0-2 were treated with a combination of paclitaxel (135 mg\/m(2) given intravenously in 3 hours) on Day 1, cisplatin (120 mg\/m(2) given intravenously in 6 hours) on Day 1, and gemcitabine (800 mg\/m(2) given intravenously in 30 minutes) on Days 1 and 8, every 4 weeks. Although responding patients were scheduled to receive consolidation radiotherapy and 24 patients received preplanned second-line chemotherapy after disease progression, the response and toxicity rates reported refer only to the chemotherapy regimen given. RESULTS: All the patients were examined for toxicity; 34 were examinable for response. An objective response was observed in 73.5% of the patients (95% confidence interval [CI], 55.6-87.1%), including 4 complete responses (11.7%). According to intention-to-treat, the overall response rate was 71.4% (95% CI, 53. 7-85.4%). After 154 courses of therapy, the median dose intensity was 131 mg\/m(2) for paclitaxel (97.3%), 117 mg\/m(2) for cisplatin (97.3%), and 1378 mg\/m(2) for gemcitabine (86.2%). World Health Organization Grade 3-4 neutropenia and thrombocytopenia occurred in 39.9% and 11.4% of patients, respectively. There was one treatment-related death. Nonhematologic toxicities were mild. After a median follow-up of 22 months, the median progression free survival rate was 7 months, and the median survival time was 16 months. CONCLUSIONS: The combination of paclitaxel, cisplatin, and gemcitabine is well tolerated and shows high activity in metastatic NSCLC. This treatment merits further comparison with other cisplatin-based regimens."],"offsets":[[156,2298]]}],"entities":[{"id":"16227","type":"Chemical","text":["Paclitaxel"],"offsets":[[0,10]],"normalized":[{"db_name":"MESH","db_id":"D017239"}]},{"id":"16228","type":"Chemical","text":["cisplatin"],"offsets":[[12,21]],"normalized":[{"db_name":"MESH","db_id":"D002945"}]},{"id":"16229","type":"Chemical","text":["gemcitabine"],"offsets":[[27,38]],"normalized":[{"db_name":"MESH","db_id":"C056507"}]},{"id":"16230","type":"Disease","text":["nonsmall cell lung carcinoma"],"offsets":[[126,154]],"normalized":[{"db_name":"MESH","db_id":"D002289"}]},{"id":"16231","type":"Chemical","text":["Cisplatin"],"offsets":[[168,177]],"normalized":[{"db_name":"MESH","db_id":"D002945"}]},{"id":"16232","type":"Disease","text":["nonsmall cell lung carcinoma"],"offsets":[[259,287]],"normalized":[{"db_name":"MESH","db_id":"D002289"}]},{"id":"16233","type":"Disease","text":["NSCLC"],"offsets":[[289,294]],"normalized":[{"db_name":"MESH","db_id":"D002289"}]},{"id":"16234","type":"Disease","text":["toxicity"],"offsets":[[501,509]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"16235","type":"Chemical","text":["paclitaxel"],"offsets":[[515,525]],"normalized":[{"db_name":"MESH","db_id":"D017239"}]},{"id":"16236","type":"Chemical","text":["cisplatin"],"offsets":[[527,536]],"normalized":[{"db_name":"MESH","db_id":"D002945"}]},{"id":"16237","type":"Chemical","text":["gemcitabine"],"offsets":[[542,553]],"normalized":[{"db_name":"MESH","db_id":"C056507"}]},{"id":"16238","type":"Disease","text":["NSCLC"],"offsets":[[586,591]],"normalized":[{"db_name":"MESH","db_id":"D002289"}]},{"id":"16239","type":"Disease","text":["NSCLC"],"offsets":[[659,664]],"normalized":[{"db_name":"MESH","db_id":"D002289"}]},{"id":"16240","type":"Chemical","text":["paclitaxel"],"offsets":[[768,778]],"normalized":[{"db_name":"MESH","db_id":"D017239"}]},{"id":"16241","type":"Chemical","text":["cisplatin"],"offsets":[[834,843]],"normalized":[{"db_name":"MESH","db_id":"D002945"}]},{"id":"16242","type":"Chemical","text":["gemcitabine"],"offsets":[[903,914]],"normalized":[{"db_name":"MESH","db_id":"C056507"}]},{"id":"16243","type":"Disease","text":["toxicity"],"offsets":[[1182,1190]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"16244","type":"Disease","text":["toxicity"],"offsets":[[1296,1304]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"16245","type":"Chemical","text":["paclitaxel"],"offsets":[[1651,1661]],"normalized":[{"db_name":"MESH","db_id":"D017239"}]},{"id":"16246","type":"Chemical","text":["cisplatin"],"offsets":[[1687,1696]],"normalized":[{"db_name":"MESH","db_id":"D002945"}]},{"id":"16247","type":"Chemical","text":["gemcitabine"],"offsets":[[1727,1738]],"normalized":[{"db_name":"MESH","db_id":"C056507"}]},{"id":"16248","type":"Disease","text":["neutropenia"],"offsets":[[1784,1795]],"normalized":[{"db_name":"MESH","db_id":"D009503"}]},{"id":"16249","type":"Disease","text":["thrombocytopenia"],"offsets":[[1800,1816]],"normalized":[{"db_name":"MESH","db_id":"D013921"}]},{"id":"16250","type":"Disease","text":["death"],"offsets":[[1904,1909]],"normalized":[{"db_name":"MESH","db_id":"D003643"}]},{"id":"16251","type":"Disease","text":["toxicities"],"offsets":[[1926,1936]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"16252","type":"Chemical","text":["paclitaxel"],"offsets":[[2119,2129]],"normalized":[{"db_name":"MESH","db_id":"D017239"}]},{"id":"16253","type":"Chemical","text":["cisplatin"],"offsets":[[2131,2140]],"normalized":[{"db_name":"MESH","db_id":"D002945"}]},{"id":"16254","type":"Chemical","text":["gemcitabine"],"offsets":[[2146,2157]],"normalized":[{"db_name":"MESH","db_id":"C056507"}]},{"id":"16255","type":"Disease","text":["NSCLC"],"offsets":[[2214,2219]],"normalized":[{"db_name":"MESH","db_id":"D002289"}]},{"id":"16256","type":"Chemical","text":["cisplatin"],"offsets":[[2273,2282]],"normalized":[{"db_name":"MESH","db_id":"D002945"}]}],"events":[],"coreferences":[],"relations":[{"id":"16257","type":"CID","arg1_id":"16228","arg2_id":"16248","normalized":[]},{"id":"16258","type":"CID","arg1_id":"16231","arg2_id":"16248","normalized":[]},{"id":"16259","type":"CID","arg1_id":"16236","arg2_id":"16248","normalized":[]},{"id":"16260","type":"CID","arg1_id":"16241","arg2_id":"16248","normalized":[]},{"id":"16261","type":"CID","arg1_id":"16246","arg2_id":"16248","normalized":[]},{"id":"16262","type":"CID","arg1_id":"16253","arg2_id":"16248","normalized":[]},{"id":"16263","type":"CID","arg1_id":"16256","arg2_id":"16248","normalized":[]},{"id":"16264","type":"CID","arg1_id":"16227","arg2_id":"16249","normalized":[]},{"id":"16265","type":"CID","arg1_id":"16235","arg2_id":"16249","normalized":[]},{"id":"16266","type":"CID","arg1_id":"16240","arg2_id":"16249","normalized":[]},{"id":"16267","type":"CID","arg1_id":"16245","arg2_id":"16249","normalized":[]},{"id":"16268","type":"CID","arg1_id":"16252","arg2_id":"16249","normalized":[]},{"id":"16269","type":"CID","arg1_id":"16229","arg2_id":"16248","normalized":[]},{"id":"16270","type":"CID","arg1_id":"16237","arg2_id":"16248","normalized":[]},{"id":"16271","type":"CID","arg1_id":"16242","arg2_id":"16248","normalized":[]},{"id":"16272","type":"CID","arg1_id":"16247","arg2_id":"16248","normalized":[]},{"id":"16273","type":"CID","arg1_id":"16254","arg2_id":"16248","normalized":[]},{"id":"16274","type":"CID","arg1_id":"16227","arg2_id":"16248","normalized":[]},{"id":"16275","type":"CID","arg1_id":"16235","arg2_id":"16248","normalized":[]},{"id":"16276","type":"CID","arg1_id":"16240","arg2_id":"16248","normalized":[]},{"id":"16277","type":"CID","arg1_id":"16245","arg2_id":"16248","normalized":[]},{"id":"16278","type":"CID","arg1_id":"16252","arg2_id":"16248","normalized":[]},{"id":"16279","type":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{"id":"16291","document_id":"8590259","passages":[{"id":"16292","type":"title","text":["Evaluation of adverse reactions of aponidine hydrochloride ophthalmic solution."],"offsets":[[0,79]]},{"id":"16293","type":"abstract","text":["We prospectively evaluated the adverse reactions of apraclonidine in 20 normal volunteers by instilling a single drop of 1% apraclonidine in their right eyes. Examinations, including blood pressure, pulse rate, conjunctiva and cornea, intraocular pressure (IOP), pupil diameter, basal tear secretion and margin reflex distance of both upper and lower eyelids, were performed prior to entry and at 1, 3, 5 and 7 hours after instillation. The ocular hypotensive effects were statistically significant for apraclonidine-treated eyes throughout the study and also statistically significant for contralateral eyes from three hours after topical administration of 1% apraclonidine. Decreases in systolic blood pressure were statistically, but not clinically, significant. No significant changes in diastolic blood pressure, pulse rate and basal tear secretion were noted. Conjunctival blanching and mydriasis were commonly found. Upper lid retraction was frequently noted. While the elevations of the upper lid margin in most subjects were not more than 2 mm and did not cause noticeable change in appearance, one subject suffered from mechanical entropion and marked corneal abrasion 3 hours after instillation of the medication. This may well be a particularly notable finding in Asian people."],"offsets":[[80,1369]]}],"entities":[{"id":"16294","type":"Chemical","text":["aponidine hydrochloride"],"offsets":[[35,58]],"normalized":[{"db_name":"MESH","db_id":"C016986"}]},{"id":"16295","type":"Chemical","text":["apraclonidine"],"offsets":[[132,145]],"normalized":[{"db_name":"MESH","db_id":"C016986"}]},{"id":"16296","type":"Chemical","text":["apraclonidine"],"offsets":[[204,217]],"normalized":[{"db_name":"MESH","db_id":"C016986"}]},{"id":"16297","type":"Disease","text":["ocular hypotensive"],"offsets":[[521,539]],"normalized":[{"db_name":"MESH","db_id":"D015814"}]},{"id":"16298","type":"Chemical","text":["apraclonidine"],"offsets":[[583,596]],"normalized":[{"db_name":"MESH","db_id":"C016986"}]},{"id":"16299","type":"Chemical","text":["apraclonidine"],"offsets":[[741,754]],"normalized":[{"db_name":"MESH","db_id":"C016986"}]},{"id":"16300","type":"Disease","text":["Decreases in systolic blood pressure"],"offsets":[[756,792]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"16301","type":"Disease","text":["Conjunctival blanching"],"offsets":[[946,968]],"normalized":[{"db_name":"MESH","db_id":"D003229"}]},{"id":"16302","type":"Disease","text":["mydriasis"],"offsets":[[973,982]],"normalized":[{"db_name":"MESH","db_id":"D015878"}]},{"id":"16303","type":"Disease","text":["entropion"],"offsets":[[1221,1230]],"normalized":[{"db_name":"MESH","db_id":"D004774"}]},{"id":"16304","type":"Disease","text":["corneal abrasion"],"offsets":[[1242,1258]],"normalized":[{"db_name":"MESH","db_id":"D003316"}]}],"events":[],"coreferences":[],"relations":[{"id":"16305","type":"CID","arg1_id":"16294","arg2_id":"16297","normalized":[]},{"id":"16306","type":"CID","arg1_id":"16295","arg2_id":"16297","normalized":[]},{"id":"16307","type":"CID","arg1_id":"16296","arg2_id":"16297","normalized":[]},{"id":"16308","type":"CID","arg1_id":"16298","arg2_id":"16297","normalized":[]},{"id":"16309","type":"CID","arg1_id":"16299","arg2_id":"16297","normalized":[]},{"id":"16310","type":"CID","arg1_id":"16294","arg2_id":"16302","normalized":[]},{"id":"16311","type":"CID","arg1_id":"16295","arg2_id":"16302","normalized":[]},{"id":"16312","type":"CID","arg1_id":"16296","arg2_id":"16302","normalized":[]},{"id":"16313","type":"CID","arg1_id":"16298","arg2_id":"16302","normalized":[]},{"id":"16314","type":"CID","arg1_id":"16299","arg2_id":"16302","normalized":[]},{"id":"16315","type":"CID","arg1_id":"16294","arg2_id":"16303","normalized":[]},{"id":"16316","type":"CID","arg1_id":"16295","arg2_id":"16303","normalized":[]},{"id":"16317","type":"CID","arg1_id":"16296","arg2_id":"16303","normalized":[]},{"id":"16318","type":"CID","arg1_id":"16298","arg2_id":"16303","normalized":[]},{"id":"16319","type":"CID","arg1_id":"16299","arg2_id":"16303","normalized":[]},{"id":"16320","type":"CID","arg1_id":"16294","arg2_id":"16304","normalized":[]},{"id":"16321","type":"CID","arg1_id":"16295","arg2_id":"16304","normalized":[]},{"id":"16322","type":"CID","arg1_id":"16296","arg2_id":"16304","normalized":[]},{"id":"16323","type":"CID","arg1_id":"16298","arg2_id":"16304","normalized":[]},{"id":"16324","type":"CID","arg1_id":"16299","arg2_id":"16304","normalized":[]},{"id":"16325","type":"CID","arg1_id":"16294","arg2_id":"16301","normalized":[]},{"id":"16326","type":"CID","arg1_id":"16295","arg2_id":"16301","normalized":[]},{"id":"16327","type":"CID","arg1_id":"16296","arg2_id":"16301","normalized":[]},{"id":"16328","type":"CID","arg1_id":"16298","arg2_id":"16301","normalized":[]},{"id":"16329","type":"CID","arg1_id":"16299","arg2_id":"16301","normalized":[]}]}
{"id":"16330","document_id":"2096243","passages":[{"id":"16331","type":"title","text":["Carmofur-induced organic mental disorders."],"offsets":[[0,42]]},{"id":"16332","type":"abstract","text":["Organic mental disorder was observed in a 29-year-old female in the prognostic period after the onset of carmofur-induced leukoencephalopathy. Symptoms such as euphoria, emotional lability and puerile attitude noted in the patient were diagnosed as organic personality syndrome according to the criteria defined in the DSM-III-R. It is referred to as a frontal lobe syndrome. Brain CT revealed a periventricular low density area in the frontal white matter and moderate dilatation of the lateral ventricles especially at the bilateral anterior horns. Consequently, carmofur-induced leukoencephalopathy may uncommonly result in organic personality syndrome in the residual state. It may be attributed to the structural damage to the frontal lobe."],"offsets":[[43,788]]}],"entities":[{"id":"16333","type":"Chemical","text":["Carmofur"],"offsets":[[0,8]],"normalized":[{"db_name":"MESH","db_id":"C017367"}]},{"id":"16334","type":"Disease","text":["organic mental disorders"],"offsets":[[17,41]],"normalized":[{"db_name":"MESH","db_id":"D019965"}]},{"id":"16335","type":"Disease","text":["Organic mental disorder"],"offsets":[[43,66]],"normalized":[{"db_name":"MESH","db_id":"D019965"}]},{"id":"16336","type":"Chemical","text":["carmofur"],"offsets":[[148,156]],"normalized":[{"db_name":"MESH","db_id":"C017367"}]},{"id":"16337","type":"Disease","text":["leukoencephalopathy"],"offsets":[[165,184]],"normalized":[{"db_name":"MESH","db_id":"D056784"}]},{"id":"16338","type":"Disease","text":["organic personality syndrome"],"offsets":[[292,320]],"normalized":[{"db_name":"MESH","db_id":"D010554"}]},{"id":"16339","type":"Disease","text":["frontal lobe syndrome"],"offsets":[[396,417]],"normalized":[{"db_name":"MESH","db_id":"D001927"}]},{"id":"16340","type":"Chemical","text":["carmofur"],"offsets":[[608,616]],"normalized":[{"db_name":"MESH","db_id":"C017367"}]},{"id":"16341","type":"Disease","text":["leukoencephalopathy"],"offsets":[[625,644]],"normalized":[{"db_name":"MESH","db_id":"D056784"}]},{"id":"16342","type":"Disease","text":["organic personality syndrome"],"offsets":[[670,698]],"normalized":[{"db_name":"MESH","db_id":"D010554"}]},{"id":"16343","type":"Disease","text":["structural damage to the frontal lobe"],"offsets":[[750,787]],"normalized":[{"db_name":"MESH","db_id":"D001927"}]}],"events":[],"coreferences":[],"relations":[{"id":"16344","type":"CID","arg1_id":"16333","arg2_id":"16337","normalized":[]},{"id":"16345","type":"CID","arg1_id":"16333","arg2_id":"16341","normalized":[]},{"id":"16346","type":"CID","arg1_id":"16336","arg2_id":"16337","normalized":[]},{"id":"16347","type":"CID","arg1_id":"16336","arg2_id":"16341","normalized":[]},{"id":"16348","type":"CID","arg1_id":"16340","arg2_id":"16337","normalized":[]},{"id":"16349","type":"CID","arg1_id":"16340","arg2_id":"16341","normalized":[]},{"id":"16350","type":"CID","arg1_id":"16333","arg2_id":"16334","normalized":[]},{"id":"16351","type":"CID","arg1_id":"16333","arg2_id":"16335","normalized":[]},{"id":"16352","type":"CID","arg1_id":"16336","arg2_id":"16334","normalized":[]},{"id":"16353","type":"CID","arg1_id":"16336","arg2_id":"16335","normalized":[]},{"id":"16354","type":"CID","arg1_id":"16340","arg2_id":"16334","normalized":[]},{"id":"16355","type":"CID","arg1_id":"16340","arg2_id":"16335","normalized":[]}]}
{"id":"16356","document_id":"6209318","passages":[{"id":"16357","type":"title","text":["International mexiletine and placebo antiarrhythmic coronary trial: I. Report on arrhythmia and other findings. Impact Research Group."],"offsets":[[0,134]]},{"id":"16358","type":"abstract","text":["The antiarrhythmic effects of the sustained release form of mexiletine (Mexitil-Perlongets) were evaluated in a double-blind placebo trial in 630 patients with recent documented myocardial infarction. The primary response variable was based on central reading of 24 hour ambulatory electrocardiographic recordings and was defined as the occurrence of 30 or more single premature ventricular complexes in any two consecutive 30 minute blocks or one or more runs of two or more premature ventricular complexes in the entire 24 hour electrocardiographic recording. Large differences, regarded as statistically significant, between the mexiletine and placebo groups were noted in that end point at months 1 and 4, but only trends were observed at month 12. These differences were observed even though the serum mexiletine levels obtained in this study were generally lower than those observed in studies that have used the regular form of the drug. There were more deaths in the mexiletine group (7.6%) than in the placebo group (4.8%); the difference was not statistically significant. The incidence of coronary events was similar in both groups. Previously recognized side effects, particularly tremor and gastrointestinal problems, were more frequent in the mexiletine group than in the placebo group."],"offsets":[[135,1435]]}],"entities":[{"id":"16359","type":"Chemical","text":["mexiletine"],"offsets":[[14,24]],"normalized":[{"db_name":"MESH","db_id":"D008801"}]},{"id":"16360","type":"Disease","text":["arrhythmia"],"offsets":[[81,91]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"16361","type":"Chemical","text":["mexiletine"],"offsets":[[195,205]],"normalized":[{"db_name":"MESH","db_id":"D008801"}]},{"id":"16362","type":"Chemical","text":["Mexitil-Perlongets"],"offsets":[[207,225]],"normalized":[{"db_name":"MESH","db_id":"D008801"}]},{"id":"16363","type":"Disease","text":["myocardial infarction"],"offsets":[[313,334]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"16364","type":"Chemical","text":["mexiletine"],"offsets":[[767,777]],"normalized":[{"db_name":"MESH","db_id":"D008801"}]},{"id":"16365","type":"Chemical","text":["mexiletine"],"offsets":[[942,952]],"normalized":[{"db_name":"MESH","db_id":"D008801"}]},{"id":"16366","type":"Disease","text":["deaths"],"offsets":[[1096,1102]],"normalized":[{"db_name":"MESH","db_id":"D003643"}]},{"id":"16367","type":"Chemical","text":["mexiletine"],"offsets":[[1110,1120]],"normalized":[{"db_name":"MESH","db_id":"D008801"}]},{"id":"16368","type":"Disease","text":["tremor"],"offsets":[[1328,1334]],"normalized":[{"db_name":"MESH","db_id":"D014202"}]},{"id":"16369","type":"Disease","text":["gastrointestinal problems"],"offsets":[[1339,1364]],"normalized":[{"db_name":"MESH","db_id":"D012817"}]},{"id":"16370","type":"Chemical","text":["mexiletine"],"offsets":[[1392,1402]],"normalized":[{"db_name":"MESH","db_id":"D008801"}]}],"events":[],"coreferences":[],"relations":[{"id":"16371","type":"CID","arg1_id":"16359","arg2_id":"16368","normalized":[]},{"id":"16372","type":"CID","arg1_id":"16361","arg2_id":"16368","normalized":[]},{"id":"16373","type":"CID","arg1_id":"16362","arg2_id":"16368","normalized":[]},{"id":"16374","type":"CID","arg1_id":"16364","arg2_id":"16368","normalized":[]},{"id":"16375","type":"CID","arg1_id":"16365","arg2_id":"16368","normalized":[]},{"id":"16376","type":"CID","arg1_id":"16367","arg2_id":"16368","normalized":[]},{"id":"16377","type":"CID","arg1_id":"16370","arg2_id":"16368","normalized":[]},{"id":"16378","type":"CID","arg1_id":"16359","arg2_id":"16369","normalized":[]},{"id":"16379","type":"CID","arg1_id":"16361","arg2_id":"16369","normalized":[]},{"id":"16380","type":"CID","arg1_id":"16362","arg2_id":"16369","normalized":[]},{"id":"16381","type":"CID","arg1_id":"16364","arg2_id":"16369","normalized":[]},{"id":"16382","type":"CID","arg1_id":"16365","arg2_id":"16369","normalized":[]},{"id":"16383","type":"CID","arg1_id":"16367","arg2_id":"16369","normalized":[]},{"id":"16384","type":"CID","arg1_id":"16370","arg2_id":"16369","normalized":[]}]}
{"id":"16385","document_id":"3615541","passages":[{"id":"16386","type":"title","text":["Regional localization of the antagonism of amphetamine-induced hyperactivity by intracerebral calcitonin injections."],"offsets":[[0,116]]},{"id":"16387","type":"abstract","text":["Calcitonin receptors are found in the brain, and intracerebral infusions of calcitonin can produce behavioral effects. Among these behavioral effects are decreases in food intake and decreases in amphetamine-induced locomotor activity. In previous experiments we found that decreases in food intake were induced by local administration of calcitonin into several hypothalamic sites and into the nucleus accumbens. In the present experiment calcitonin decreased locomotor activity when locally injected into the same sites where it decreases food intake. The areas where calcitonin is most effective in decreasing locomotor activity are located in the hypothalamus and nucleus accumbens, suggesting that these areas are the major sites of action of calcitonin in inhibiting amphetamine-induced locomotor activity."],"offsets":[[117,929]]}],"entities":[{"id":"16388","type":"Chemical","text":["amphetamine"],"offsets":[[43,54]],"normalized":[{"db_name":"MESH","db_id":"D000661"}]},{"id":"16389","type":"Disease","text":["hyperactivity"],"offsets":[[63,76]],"normalized":[{"db_name":"MESH","db_id":"D006948"}]},{"id":"16390","type":"Chemical","text":["calcitonin"],"offsets":[[94,104]],"normalized":[{"db_name":"MESH","db_id":"D002116"}]},{"id":"16391","type":"Chemical","text":["Calcitonin"],"offsets":[[117,127]],"normalized":[{"db_name":"MESH","db_id":"D002116"}]},{"id":"16392","type":"Chemical","text":["calcitonin"],"offsets":[[193,203]],"normalized":[{"db_name":"MESH","db_id":"D002116"}]},{"id":"16393","type":"Chemical","text":["amphetamine"],"offsets":[[313,324]],"normalized":[{"db_name":"MESH","db_id":"D000661"}]},{"id":"16394","type":"Chemical","text":["calcitonin"],"offsets":[[456,466]],"normalized":[{"db_name":"MESH","db_id":"D002116"}]},{"id":"16395","type":"Chemical","text":["calcitonin"],"offsets":[[557,567]],"normalized":[{"db_name":"MESH","db_id":"D002116"}]},{"id":"16396","type":"Chemical","text":["calcitonin"],"offsets":[[687,697]],"normalized":[{"db_name":"MESH","db_id":"D002116"}]},{"id":"16397","type":"Chemical","text":["calcitonin"],"offsets":[[865,875]],"normalized":[{"db_name":"MESH","db_id":"D002116"}]},{"id":"16398","type":"Chemical","text":["amphetamine"],"offsets":[[890,901]],"normalized":[{"db_name":"MESH","db_id":"D000661"}]}],"events":[],"coreferences":[],"relations":[{"id":"16399","type":"CID","arg1_id":"16388","arg2_id":"16389","normalized":[]},{"id":"16400","type":"CID","arg1_id":"16393","arg2_id":"16389","normalized":[]},{"id":"16401","type":"CID","arg1_id":"16398","arg2_id":"16389","normalized":[]}]}
{"id":"16402","document_id":"8953972","passages":[{"id":"16403","type":"title","text":["Fatal intracranial bleeding associated with prehospital use of epinephrine."],"offsets":[[0,75]]},{"id":"16404","type":"abstract","text":["We present a case of paramedic misjudgment in the execution of a protocol for the treatment of allergic reaction in a case of pulmonary edema with wheezing. The sudden onset of respiratory distress, rash, and a history of a new medicine led the two paramedics on the scene to administer subcutaneous epinephrine. Subsequently, acute cardiac arrest and fatal subarachnoid hemorrhage occurred. Epinephrine has a proven role in cardiac arrest in prehospital care; however, use by paramedics in patients with suspected allergic reaction and severe hypertension should be viewed with caution."],"offsets":[[76,663]]}],"entities":[{"id":"16405","type":"Disease","text":["intracranial bleeding"],"offsets":[[6,27]],"normalized":[{"db_name":"MESH","db_id":"D013345"}]},{"id":"16406","type":"Chemical","text":["epinephrine"],"offsets":[[63,74]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"16407","type":"Disease","text":["allergic reaction"],"offsets":[[171,188]],"normalized":[{"db_name":"MESH","db_id":"D004342"}]},{"id":"16408","type":"Disease","text":["pulmonary edema"],"offsets":[[202,217]],"normalized":[{"db_name":"MESH","db_id":"D011654"}]},{"id":"16409","type":"Disease","text":["wheezing"],"offsets":[[223,231]],"normalized":[{"db_name":"MESH","db_id":"D012135"}]},{"id":"16410","type":"Disease","text":["respiratory distress"],"offsets":[[253,273]],"normalized":[{"db_name":"MESH","db_id":"D012128"}]},{"id":"16411","type":"Disease","text":["rash"],"offsets":[[275,279]],"normalized":[{"db_name":"MESH","db_id":"D005076"}]},{"id":"16412","type":"Chemical","text":["epinephrine"],"offsets":[[376,387]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"16413","type":"Disease","text":["cardiac arrest"],"offsets":[[409,423]],"normalized":[{"db_name":"MESH","db_id":"D006323"}]},{"id":"16414","type":"Disease","text":["subarachnoid hemorrhage"],"offsets":[[434,457]],"normalized":[{"db_name":"MESH","db_id":"D013345"}]},{"id":"16415","type":"Chemical","text":["Epinephrine"],"offsets":[[468,479]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"16416","type":"Disease","text":["cardiac arrest"],"offsets":[[501,515]],"normalized":[{"db_name":"MESH","db_id":"D006323"}]},{"id":"16417","type":"Disease","text":["allergic reaction"],"offsets":[[591,608]],"normalized":[{"db_name":"MESH","db_id":"D004342"}]},{"id":"16418","type":"Disease","text":["hypertension"],"offsets":[[620,632]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]}],"events":[],"coreferences":[],"relations":[{"id":"16419","type":"CID","arg1_id":"16406","arg2_id":"16405","normalized":[]},{"id":"16420","type":"CID","arg1_id":"16406","arg2_id":"16414","normalized":[]},{"id":"16421","type":"CID","arg1_id":"16412","arg2_id":"16405","normalized":[]},{"id":"16422","type":"CID","arg1_id":"16412","arg2_id":"16414","normalized":[]},{"id":"16423","type":"CID","arg1_id":"16415","arg2_id":"16405","normalized":[]},{"id":"16424","type":"CID","arg1_id":"16415","arg2_id":"16414","normalized":[]},{"id":"16425","type":"CID","arg1_id":"16406","arg2_id":"16413","normalized":[]},{"id":"16426","type":"CID","arg1_id":"16406","arg2_id":"16416","normalized":[]},{"id":"16427","type":"CID","arg1_id":"16412","arg2_id":"16413","normalized":[]},{"id":"16428","type":"CID","arg1_id":"16412","arg2_id":"16416","normalized":[]},{"id":"16429","type":"CID","arg1_id":"16415","arg2_id":"16413","normalized":[]},{"id":"16430","type":"CID","arg1_id":"16415","arg2_id":"16416","normalized":[]}]}
{"id":"16431","document_id":"3782049","passages":[{"id":"16432","type":"title","text":["A case of massive rhabdomyolysis following molindone administration."],"offsets":[[0,68]]},{"id":"16433","type":"abstract","text":["Rhabdomyolysis is a potentially lethal syndrome that psychiatric patients seem predisposed to develop. The clinical signs and symptoms, typical laboratory features, and complications of rhabdomyolysis are presented. The case of a schizophrenic patient is reported to illustrate massive rhabdomyolysis and subsequent acute renal failure following molindone administration. Physicians who prescribe molindone should be aware of this reaction."],"offsets":[[69,509]]}],"entities":[{"id":"16434","type":"Disease","text":["rhabdomyolysis"],"offsets":[[18,32]],"normalized":[{"db_name":"MESH","db_id":"D012206"}]},{"id":"16435","type":"Chemical","text":["molindone"],"offsets":[[43,52]],"normalized":[{"db_name":"MESH","db_id":"D008972"}]},{"id":"16436","type":"Disease","text":["Rhabdomyolysis"],"offsets":[[69,83]],"normalized":[{"db_name":"MESH","db_id":"D012206"}]},{"id":"16437","type":"Disease","text":["psychiatric"],"offsets":[[122,133]],"normalized":[{"db_name":"MESH","db_id":"D001523"}]},{"id":"16438","type":"Disease","text":["rhabdomyolysis"],"offsets":[[255,269]],"normalized":[{"db_name":"MESH","db_id":"D012206"}]},{"id":"16439","type":"Disease","text":["schizophrenic"],"offsets":[[299,312]],"normalized":[{"db_name":"MESH","db_id":"D012559"}]},{"id":"16440","type":"Disease","text":["rhabdomyolysis"],"offsets":[[355,369]],"normalized":[{"db_name":"MESH","db_id":"D012206"}]},{"id":"16441","type":"Disease","text":["acute renal failure"],"offsets":[[385,404]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"16442","type":"Chemical","text":["molindone"],"offsets":[[415,424]],"normalized":[{"db_name":"MESH","db_id":"D008972"}]},{"id":"16443","type":"Chemical","text":["molindone"],"offsets":[[466,475]],"normalized":[{"db_name":"MESH","db_id":"D008972"}]}],"events":[],"coreferences":[],"relations":[{"id":"16444","type":"CID","arg1_id":"16435","arg2_id":"16434","normalized":[]},{"id":"16445","type":"CID","arg1_id":"16435","arg2_id":"16436","normalized":[]},{"id":"16446","type":"CID","arg1_id":"16435","arg2_id":"16438","normalized":[]},{"id":"16447","type":"CID","arg1_id":"16435","arg2_id":"16440","normalized":[]},{"id":"16448","type":"CID","arg1_id":"16442","arg2_id":"16434","normalized":[]},{"id":"16449","type":"CID","arg1_id":"16442","arg2_id":"16436","normalized":[]},{"id":"16450","type":"CID","arg1_id":"16442","arg2_id":"16438","normalized":[]},{"id":"16451","type":"CID","arg1_id":"16442","arg2_id":"16440","normalized":[]},{"id":"16452","type":"CID","arg1_id":"16443","arg2_id":"16434","normalized":[]},{"id":"16453","type":"CID","arg1_id":"16443","arg2_id":"16436","normalized":[]},{"id":"16454","type":"CID","arg1_id":"16443","arg2_id":"16438","normalized":[]},{"id":"16455","type":"CID","arg1_id":"16443","arg2_id":"16440","normalized":[]},{"id":"16456","type":"CID","arg1_id":"16435","arg2_id":"16441","normalized":[]},{"id":"16457","type":"CID","arg1_id":"16442","arg2_id":"16441","normalized":[]},{"id":"16458","type":"CID","arg1_id":"16443","arg2_id":"16441","normalized":[]}]}
{"id":"16459","document_id":"9100294","passages":[{"id":"16460","type":"title","text":["Cardiovascular alterations in rat fetuses exposed to calcium channel blockers."],"offsets":[[0,78]]},{"id":"16461","type":"abstract","text":["Preclinical toxicologic investigation suggested that a new calcium channel blocker, Ro 40-5967, induced cardiovascular alterations in rat fetuses exposed to this agent during organogenesis. The present study was designed to investigate the hypothesis that calcium channel blockers in general induce cardiovascular malformations indicating a pharmacologic class effect. We studied three calcium channel blockers of different structure, nifedipine, diltiazem, and verapamil, along with the new agent. Pregnant rats were administered one of these calcium channel blockers during the period of cardiac morphogenesis and the offspring examined on day 20 of gestation for cardiovascular malformations. A low incidence of cardiovascular malformations was observed after exposure to each of the four calcium channel blockers, but this incidence was statistically significant only for verapamil and nifedipine. All four agents were associated with aortic arch branching variants, although significantly increased only for Ro 40-5967 and verapamil."],"offsets":[[79,1117]]}],"entities":[{"id":"16462","type":"Disease","text":["Cardiovascular alterations"],"offsets":[[0,26]],"normalized":[{"db_name":"MESH","db_id":"D018376"}]},{"id":"16463","type":"Chemical","text":["calcium"],"offsets":[[53,60]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"16464","type":"Chemical","text":["calcium"],"offsets":[[138,145]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"16465","type":"Chemical","text":["Ro 40-5967"],"offsets":[[163,173]],"normalized":[{"db_name":"MESH","db_id":"D020748"}]},{"id":"16466","type":"Disease","text":["cardiovascular alterations"],"offsets":[[183,209]],"normalized":[{"db_name":"MESH","db_id":"D018376"}]},{"id":"16467","type":"Chemical","text":["calcium"],"offsets":[[335,342]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"16468","type":"Disease","text":["cardiovascular malformations"],"offsets":[[378,406]],"normalized":[{"db_name":"MESH","db_id":"D018376"}]},{"id":"16469","type":"Chemical","text":["calcium"],"offsets":[[465,472]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"16470","type":"Chemical","text":["nifedipine"],"offsets":[[514,524]],"normalized":[{"db_name":"MESH","db_id":"D009543"}]},{"id":"16471","type":"Chemical","text":["diltiazem"],"offsets":[[526,535]],"normalized":[{"db_name":"MESH","db_id":"D004110"}]},{"id":"16472","type":"Chemical","text":["verapamil"],"offsets":[[541,550]],"normalized":[{"db_name":"MESH","db_id":"D014700"}]},{"id":"16473","type":"Chemical","text":["calcium"],"offsets":[[623,630]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"16474","type":"Disease","text":["cardiovascular malformations"],"offsets":[[745,773]],"normalized":[{"db_name":"MESH","db_id":"D018376"}]},{"id":"16475","type":"Disease","text":["cardiovascular malformations"],"offsets":[[794,822]],"normalized":[{"db_name":"MESH","db_id":"D018376"}]},{"id":"16476","type":"Chemical","text":["calcium"],"offsets":[[871,878]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"16477","type":"Chemical","text":["verapamil"],"offsets":[[955,964]],"normalized":[{"db_name":"MESH","db_id":"D014700"}]},{"id":"16478","type":"Chemical","text":["nifedipine"],"offsets":[[969,979]],"normalized":[{"db_name":"MESH","db_id":"D009543"}]},{"id":"16479","type":"Chemical","text":["Ro 40-5967"],"offsets":[[1092,1102]],"normalized":[{"db_name":"MESH","db_id":"D020748"}]},{"id":"16480","type":"Chemical","text":["verapamil"],"offsets":[[1107,1116]],"normalized":[{"db_name":"MESH","db_id":"D014700"}]}],"events":[],"coreferences":[],"relations":[{"id":"16481","type":"CID","arg1_id":"16472","arg2_id":"16462","normalized":[]},{"id":"16482","type":"CID","arg1_id":"16472","arg2_id":"16466","normalized":[]},{"id":"16483","type":"CID","arg1_id":"16472","arg2_id":"16468","normalized":[]},{"id":"16484","type":"CID","arg1_id":"16472","arg2_id":"16474","normalized":[]},{"id":"16485","type":"CID","arg1_id":"16472","arg2_id":"16475","normalized":[]},{"id":"16486","type":"CID","arg1_id":"16477","arg2_id":"16462","normalized":[]},{"id":"16487","type":"CID","arg1_id":"16477","arg2_id":"16466","normalized":[]},{"id":"16488","type":"CID","arg1_id":"16477","arg2_id":"16468","normalized":[]},{"id":"16489","type":"CID","arg1_id":"16477","arg2_id":"16474","normalized":[]},{"id":"16490","type":"CID","arg1_id":"16477","arg2_id":"16475","normalized":[]},{"id":"16491","type":"CID","arg1_id":"16480","arg2_id":"16462","normalized":[]},{"id":"16492","type":"CID","arg1_id":"16480","arg2_id":"16466","normalized":[]},{"id":"16493","type":"CID","arg1_id":"16480","arg2_id":"16468","normalized":[]},{"id":"16494","type":"CID","arg1_id":"16480","arg2_id":"16474","normalized":[]},{"id":"16495","type":"CID","arg1_id":"16480","arg2_id":"16475","normalized":[]},{"id":"16496","type":"CID","arg1_id":"16470","arg2_id":"16462","normalized":[]},{"id":"16497","type":"CID","arg1_id":"16470","arg2_id":"16466","normalized":[]},{"id":"16498","type":"CID","arg1_id":"16470","arg2_id":"16468","normalized":[]},{"id":"16499","type":"CID","arg1_id":"16470","arg2_id":"16474","normalized":[]},{"id":"16500","type":"CID","arg1_id":"16470","arg2_id":"16475","normalized":[]},{"id":"16501","type":"CID","arg1_id":"16478","arg2_id":"16462","normalized":[]},{"id":"16502","type":"CID","arg1_id":"16478","arg2_id":"16466","normalized":[]},{"id":"16503","type":"CID","arg1_id":"16478","arg2_id":"16468","normalized":[]},{"id":"16504","type":"CID","arg1_id":"16478","arg2_id":"16474","normalized":[]},{"id":"16505","type":"CID","arg1_id":"16478","arg2_id":"16475","normalized":[]},{"id":"16506","type":"CID","arg1_id":"16465","arg2_id":"16462","normalized":[]},{"id":"16507","type":"CID","arg1_id":"16465","arg2_id":"16466","normalized":[]},{"id":"16508","type":"CID","arg1_id":"16465","arg2_id":"16468","normalized":[]},{"id":"16509","type":"CID","arg1_id":"16465","arg2_id":"16474","normalized":[]},{"id":"16510","type":"CID","arg1_id":"16465","arg2_id":"16475","normalized":[]},{"id":"16511","type":"CID","arg1_id":"16479","arg2_id":"16462","normalized":[]},{"id":"16512","type":"CID","arg1_id":"16479","arg2_id":"16466","normalized":[]},{"id":"16513","type":"CID","arg1_id":"16479","arg2_id":"16468","normalized":[]},{"id":"16514","type":"CID","arg1_id":"16479","arg2_id":"16474","normalized":[]},{"id":"16515","type":"CID","arg1_id":"16479","arg2_id":"16475","normalized":[]}]}
{"id":"16516","document_id":"19889778","passages":[{"id":"16517","type":"title","text":["Differential impact of immune escape mutations G145R and P120T on the replication of lamivudine-resistant hepatitis B virus e antigen-positive and -negative strains."],"offsets":[[0,165]]},{"id":"16518","type":"abstract","text":["Immune escape variants of the hepatitis B virus (HBV) represent an emerging clinical challenge, because they can be associated with vaccine escape, HBV reactivation, and failure of diagnostic tests. Recent data suggest a preferential selection of immune escape mutants in distinct peripheral blood leukocyte compartments of infected individuals. We therefore systematically analyzed the functional impact of the most prevalent immune escape variants, the sG145R and sP120T mutants, on the viral replication efficacy and antiviral drug susceptibility of common treatment-associated mutants with resistance to lamivudine (LAM) and\/or HBeAg negativity. Replication-competent HBV strains with sG145R or sP120T and LAM resistance (rtM204I or rtL180M\/rtM204V) were generated on an HBeAg-positive and an HBeAg-negative background with precore (PC) and basal core promoter (BCP) mutants. The sG145R mutation strongly reduced HBsAg levels and was able to fully restore the impaired replication of LAM-resistant HBV mutants to the levels of wild-type HBV, and PC or BCP mutations further enhanced viral replication. Although the sP120T substitution also impaired HBsAg secretion, it did not enhance the replication of LAM-resistant clones. However, the concomitant occurrence of HBeAg negativity (PC\/BCP), sP120T, and LAM resistance resulted in the restoration of replication to levels of wild-type HBV. In all clones with combined immune escape and LAM resistance mutations, the nucleotide analogues adefovir and tenofovir remained effective in suppressing viral replication in vitro. These findings reveal the differential impact of immune escape variants on the replication and drug susceptibility of complex HBV mutants, supporting the need of close surveillance and treatment adjustment in response to the selection of distinct mutational patterns."],"offsets":[[166,2009]]}],"entities":[{"id":"16519","type":"Chemical","text":["lamivudine"],"offsets":[[85,95]],"normalized":[{"db_name":"MESH","db_id":"D019259"}]},{"id":"16520","type":"Chemical","text":["hepatitis B virus e antigen"],"offsets":[[106,133]],"normalized":[{"db_name":"MESH","db_id":"D006513"}]},{"id":"16521","type":"Disease","text":["hepatitis B"],"offsets":[[196,207]],"normalized":[{"db_name":"MESH","db_id":"D006509"}]},{"id":"16522","type":"Chemical","text":["lamivudine"],"offsets":[[774,784]],"normalized":[{"db_name":"MESH","db_id":"D019259"}]},{"id":"16523","type":"Chemical","text":["LAM"],"offsets":[[786,789]],"normalized":[{"db_name":"MESH","db_id":"D019259"}]},{"id":"16524","type":"Chemical","text":["HBeAg"],"offsets":[[798,803]],"normalized":[{"db_name":"MESH","db_id":"D006513"}]},{"id":"16525","type":"Chemical","text":["LAM"],"offsets":[[876,879]],"normalized":[{"db_name":"MESH","db_id":"D019259"}]},{"id":"16526","type":"Chemical","text":["HBeAg"],"offsets":[[941,946]],"normalized":[{"db_name":"MESH","db_id":"D006513"}]},{"id":"16527","type":"Chemical","text":["HBeAg"],"offsets":[[963,968]],"normalized":[{"db_name":"MESH","db_id":"D006513"}]},{"id":"16528","type":"Chemical","text":["HBsAg"],"offsets":[[1083,1088]],"normalized":[{"db_name":"MESH","db_id":"D006514"}]},{"id":"16529","type":"Chemical","text":["LAM"],"offsets":[[1154,1157]],"normalized":[{"db_name":"MESH","db_id":"D019259"}]},{"id":"16530","type":"Chemical","text":["HBsAg"],"offsets":[[1319,1324]],"normalized":[{"db_name":"MESH","db_id":"D006514"}]},{"id":"16531","type":"Chemical","text":["LAM"],"offsets":[[1374,1377]],"normalized":[{"db_name":"MESH","db_id":"D019259"}]},{"id":"16532","type":"Chemical","text":["HBeAg"],"offsets":[[1435,1440]],"normalized":[{"db_name":"MESH","db_id":"D006513"}]},{"id":"16533","type":"Chemical","text":["LAM"],"offsets":[[1474,1477]],"normalized":[{"db_name":"MESH","db_id":"D019259"}]},{"id":"16534","type":"Chemical","text":["LAM"],"offsets":[[1606,1609]],"normalized":[{"db_name":"MESH","db_id":"D019259"}]},{"id":"16535","type":"Chemical","text":["nucleotide"],"offsets":[[1636,1646]],"normalized":[{"db_name":"MESH","db_id":"D009711"}]},{"id":"16536","type":"Chemical","text":["adefovir"],"offsets":[[1657,1665]],"normalized":[{"db_name":"MESH","db_id":"C053001"}]},{"id":"16537","type":"Chemical","text":["tenofovir"],"offsets":[[1670,1679]],"normalized":[{"db_name":"MESH","db_id":"C096918"}]}],"events":[],"coreferences":[],"relations":[{"id":"16538","type":"CID","arg1_id":"16528","arg2_id":"16521","normalized":[]},{"id":"16539","type":"CID","arg1_id":"16530","arg2_id":"16521","normalized":[]},{"id":"16540","type":"CID","arg1_id":"16520","arg2_id":"16521","normalized":[]},{"id":"16541","type":"CID","arg1_id":"16524","arg2_id":"16521","normalized":[]},{"id":"16542","type":"CID","arg1_id":"16526","arg2_id":"16521","normalized":[]},{"id":"16543","type":"CID","arg1_id":"16527","arg2_id":"16521","normalized":[]},{"id":"16544","type":"CID","arg1_id":"16532","arg2_id":"16521","normalized":[]}]}
{"id":"16545","document_id":"15278670","passages":[{"id":"16546","type":"title","text":["The effects of sevoflurane on lidocaine-induced convulsions."],"offsets":[[0,60]]},{"id":"16547","type":"abstract","text":["The influence of sevoflurane on lidocaine-induced convulsions was studied in cats. The convulsive threshold (mean +\/- SD) was 41.4 +\/- 6.5 mg. l(-1) with lidocaine infusion (6 mg.kg(-1).min(-1)), increasing significantly to 66.6 +\/- 10.9 mg. l(-1) when the end-tidal concentration of sevoflurane was 0.8%. However, the threshold (61.6 +\/- 8.7 mg. l(-1)) during 1.6% sevoflurane was not significant from that during 0.8% sevoflurane, indicating a celling effect. There was no significant difference in the convulsive threshold between sevoflurane and enflurane. The rise in blood pressure became less marked when higher concentrations of sevoflurane or enflurane were administered and the blood pressure at convulsions decreased significantly in 1.6% sevoflurane, and in 0.8% and 1.6% enflurane. However, there was no significant difference in the lidocaine concentrations measured when the systolic blood pressure became 70 mmHg. Apamin, a selective blocker of calcium-dependent potassium channels, was administered intracerebroventricularly in rats anesthetized with 0.8% sevoflurane to investigate the mechanism of the anticonvulsive effects. Apamin (10 ng) had a tendency to decrease the convulsive threshold (21.6 +\/- 2.2 to 19.9 +\/- 2.5 mg. l(-1)) but this was not statistically significant. It is suggested that sevoflurane reduces the convulsive effect of lidocaine toxicity but carries some risk due to circulatory depression."],"offsets":[[61,1495]]}],"entities":[{"id":"16548","type":"Chemical","text":["sevoflurane"],"offsets":[[15,26]],"normalized":[{"db_name":"MESH","db_id":"C009250"}]},{"id":"16549","type":"Chemical","text":["lidocaine"],"offsets":[[30,39]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"16550","type":"Disease","text":["convulsions"],"offsets":[[48,59]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"16551","type":"Chemical","text":["sevoflurane"],"offsets":[[78,89]],"normalized":[{"db_name":"MESH","db_id":"C009250"}]},{"id":"16552","type":"Chemical","text":["lidocaine"],"offsets":[[93,102]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"16553","type":"Disease","text":["convulsions"],"offsets":[[111,122]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"16554","type":"Disease","text":["convulsive"],"offsets":[[148,158]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"16555","type":"Chemical","text":["lidocaine"],"offsets":[[215,224]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"16556","type":"Chemical","text":["sevoflurane"],"offsets":[[345,356]],"normalized":[{"db_name":"MESH","db_id":"C009250"}]},{"id":"16557","type":"Chemical","text":["sevoflurane"],"offsets":[[427,438]],"normalized":[{"db_name":"MESH","db_id":"C009250"}]},{"id":"16558","type":"Chemical","text":["sevoflurane"],"offsets":[[481,492]],"normalized":[{"db_name":"MESH","db_id":"C009250"}]},{"id":"16559","type":"Disease","text":["convulsive"],"offsets":[[566,576]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"16560","type":"Chemical","text":["sevoflurane"],"offsets":[[595,606]],"normalized":[{"db_name":"MESH","db_id":"C009250"}]},{"id":"16561","type":"Chemical","text":["enflurane"],"offsets":[[611,620]],"normalized":[{"db_name":"MESH","db_id":"D004737"}]},{"id":"16562","type":"Chemical","text":["sevoflurane"],"offsets":[[698,709]],"normalized":[{"db_name":"MESH","db_id":"C009250"}]},{"id":"16563","type":"Chemical","text":["enflurane"],"offsets":[[713,722]],"normalized":[{"db_name":"MESH","db_id":"D004737"}]},{"id":"16564","type":"Disease","text":["convulsions"],"offsets":[[767,778]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"16565","type":"Chemical","text":["sevoflurane"],"offsets":[[811,822]],"normalized":[{"db_name":"MESH","db_id":"C009250"}]},{"id":"16566","type":"Chemical","text":["enflurane"],"offsets":[[845,854]],"normalized":[{"db_name":"MESH","db_id":"D004737"}]},{"id":"16567","type":"Chemical","text":["lidocaine"],"offsets":[[908,917]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"16568","type":"Chemical","text":["Apamin"],"offsets":[[991,997]],"normalized":[{"db_name":"MESH","db_id":"D001030"}]},{"id":"16569","type":"Chemical","text":["calcium"],"offsets":[[1022,1029]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"16570","type":"Chemical","text":["potassium"],"offsets":[[1040,1049]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"16571","type":"Chemical","text":["sevoflurane"],"offsets":[[1134,1145]],"normalized":[{"db_name":"MESH","db_id":"C009250"}]},{"id":"16572","type":"Chemical","text":["Apamin"],"offsets":[[1206,1212]],"normalized":[{"db_name":"MESH","db_id":"D001030"}]},{"id":"16573","type":"Disease","text":["convulsive"],"offsets":[[1252,1262]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"16574","type":"Chemical","text":["sevoflurane"],"offsets":[[1379,1390]],"normalized":[{"db_name":"MESH","db_id":"C009250"}]},{"id":"16575","type":"Disease","text":["convulsive"],"offsets":[[1403,1413]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"16576","type":"Chemical","text":["lidocaine"],"offsets":[[1424,1433]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"16577","type":"Disease","text":["toxicity"],"offsets":[[1434,1442]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"16578","type":"Disease","text":["depression"],"offsets":[[1484,1494]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]}],"events":[],"coreferences":[],"relations":[{"id":"16579","type":"CID","arg1_id":"16549","arg2_id":"16550","normalized":[]},{"id":"16580","type":"CID","arg1_id":"16549","arg2_id":"16553","normalized":[]},{"id":"16581","type":"CID","arg1_id":"16549","arg2_id":"16554","normalized":[]},{"id":"16582","type":"CID","arg1_id":"16549","arg2_id":"16559","normalized":[]},{"id":"16583","type":"CID","arg1_id":"16549","arg2_id":"16564","normalized":[]},{"id":"16584","type":"CID","arg1_id":"16549","arg2_id":"16573","normalized":[]},{"id":"16585","type":"CID","arg1_id":"16549","arg2_id":"16575","normalized":[]},{"id":"16586","type":"CID","arg1_id":"16552","arg2_id":"16550","normalized":[]},{"id":"16587","type":"CID","arg1_id":"16552","arg2_id":"16553","normalized":[]},{"id":"16588","type":"CID","arg1_id":"16552","arg2_id":"16554","normalized":[]},{"id":"16589","type":"CID","arg1_id":"16552","arg2_id":"16559","normalized":[]},{"id":"16590","type":"CID","arg1_i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{"id":"16614","document_id":"17042910","passages":[{"id":"16615","type":"title","text":["Anti-oxidant effects of atorvastatin in dexamethasone-induced hypertension in the rat."],"offsets":[[0,86]]},{"id":"16616","type":"abstract","text":["1. Dexamethasone (Dex)-induced hypertension is characterized by endothelial dysfunction associated with nitric oxide (NO) deficiency and increased superoxide (O2-) production. Atorvastatin (Ato) possesses pleiotropic properties that have been reported to improve endothelial function through increased availability of NO and reduced O2- production in various forms of hypertension. In the present study, we investigated whether 50 mg\/kg per day, p.o., Ato could prevent endothelial NO synthase (eNOS) downregulation and the increase in O2- in Sprague-Dawley (SD) rats, thereby reducing blood pressure. 2. Male SD rats (n = 30) were treated with Ato (50 mg\/kg per day in drinking water) or tap water for 15 days. Dexamethasone (10 microg\/kg per day, s.c.) or saline was started after 4 days in Ato-treated and non-treated rats and continued for 11-13 days. Systolic blood pressure (SBP) was measured on alternate days using the tail-cuff method. Endothelial function was assessed by acetylcholine-induced vasorelaxation and phenylephrine-induced vasoconstriction in aortic segments. Vascular eNOS mRNA was assessed by semi-quantitative reverse transcription-polymerase chain reaction. 3. In rats treated with Dex alone, SBP was increased from 109 +\/- 2 to 133 +\/- 2 mmHg on Days 4 and Day 14, respectively (P < 0.001). In the Ato + Dex group, SBP was increased from 113 +\/- 2 to 119 +\/- 2 mmHg on Days 4 to 14, respectively (P < 0.001), but was significantly lower than SBP in the group treated with Dex alone (P < 0.05). Endothelial-dependent relaxation and eNOS mRNA expression were greater in the Dex + Ato group than in the Dex only group (P < 0.05 and P < 0.0001, respectively). Aortic superoxide production was lower in the Dex + Ato group compared with the group treated with Dex alone (P < 0.0001). 4. Treatment with Ato improved endothelial function, reduced superoxide production and reduced SBP in Dex-treated SD rats."],"offsets":[[87,2015]]}],"entities":[{"id":"16617","type":"Chemical","text":["atorvastatin"],"offsets":[[24,36]],"normalized":[{"db_name":"MESH","db_id":"C065179"}]},{"id":"16618","type":"Chemical","text":["dexamethasone"],"offsets":[[40,53]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"16619","type":"Disease","text":["hypertension"],"offsets":[[62,74]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"16620","type":"Chemical","text":["Dexamethasone"],"offsets":[[90,103]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"16621","type":"Chemical","text":["Dex"],"offsets":[[105,108]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"16622","type":"Disease","text":["hypertension"],"offsets":[[118,130]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"16623","type":"Chemical","text":["nitric 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{"id":"16690","document_id":"11897407","passages":[{"id":"16691","type":"title","text":["99mTc-glucarate for detection of isoproterenol-induced myocardial infarction in rats."],"offsets":[[0,85]]},{"id":"16692","type":"abstract","text":["Infarct-avid radiopharmaceuticals are necessary for rapid and timely diagnosis of acute myocardial infarction. The animal model used to produce infarction implies artery ligation but chemical induction can be easily obtained with isoproterenol. A new infarct-avid radiopharmaceutical based on glucaric acid was prepared in the hospital radiopharmacy of the INCMNSZ. 99mTc-glucarate was easy to prepare, stable for 96 h and was used to study its biodistribution in rats with isoproterenol-induced acute myocardial infarction. Histological studies demonstrated that the rats developed an infarct 18 h after isoproterenol administration. The rat biodistribution studies showed a rapid blood clearance via the kidneys. Thirty minutes after 99mTc-glucarate administration the standardised heart uptake value S(h)UV was 4.7 in infarcted rat heart which is six times more than in normal rats. ROIs drawn over the gamma camera images showed a ratio of 4.4. The high image quality suggests that high contrast images can be obtained in humans and the 96 h stability makes it an ideal agent to detect, in patients, early cardiac infarction."],"offsets":[[86,1215]]}],"entities":[{"id":"16693","type":"Chemical","text":["99mTc-glucarate"],"offsets":[[0,15]],"normalized":[{"db_name":"MESH","db_id":"C067171"}]},{"id":"16694","type":"Chemical","text":["isoproterenol"],"offsets":[[33,46]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"16695","type":"Disease","text":["myocardial infarction"],"offsets":[[55,76]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"16696","type":"Disease","text":["Infarct"],"offsets":[[86,93]],"normalized":[{"db_name":"MESH","db_id":"D007238"}]},{"id":"16697","type":"Disease","text":["myocardial infarction"],"offsets":[[174,195]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"16698","type":"Disease","text":["infarction"],"offsets":[[230,240]],"normalized":[{"db_name":"MESH","db_id":"D007238"}]},{"id":"16699","type":"Chemical","text":["isoproterenol"],"offsets":[[316,329]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"16700","type":"Disease","text":["infarct"],"offsets":[[337,344]],"normalized":[{"db_name":"MESH","db_id":"D007238"}]},{"id":"16701","type":"Chemical","text":["glucaric acid"],"offsets":[[379,392]],"normalized":[{"db_name":"MESH","db_id":"D005937"}]},{"id":"16702","type":"Chemical","text":["99mTc-glucarate"],"offsets":[[452,467]],"normalized":[{"db_name":"MESH","db_id":"C067171"}]},{"id":"16703","type":"Chemical","text":["isoproterenol"],"offsets":[[560,573]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"16704","type":"Disease","text":["myocardial infarction"],"offsets":[[588,609]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"16705","type":"Disease","text":["infarct"],"offsets":[[672,679]],"normalized":[{"db_name":"MESH","db_id":"D007238"}]},{"id":"16706","type":"Chemical","text":["isoproterenol"],"offsets":[[691,704]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"16707","type":"Chemical","text":["99mTc-glucarate"],"offsets":[[822,837]],"normalized":[{"db_name":"MESH","db_id":"C067171"}]},{"id":"16708","type":"Disease","text":["cardiac infarction"],"offsets":[[1196,1214]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]}],"events":[],"coreferences":[],"relations":[{"id":"16709","type":"CID","arg1_id":"16694","arg2_id":"16695","normalized":[]},{"id":"16710","type":"CID","arg1_id":"16694","arg2_id":"16697","normalized":[]},{"id":"16711","type":"CID","arg1_id":"16694","arg2_id":"16704","normalized":[]},{"id":"16712","type":"CID","arg1_id":"16694","arg2_id":"16708","normalized":[]},{"id":"16713","type":"CID","arg1_id":"16699","arg2_id":"16695","normalized":[]},{"id":"16714","type":"CID","arg1_id":"16699","arg2_id":"16697","normalized":[]},{"id":"16715","type":"CID","arg1_id":"16699","arg2_id":"16704","normalized":[]},{"id":"16716","type":"CID","arg1_id":"16699","arg2_id":"16708","normalized":[]},{"id":"16717","type":"CID","arg1_id":"16703","arg2_id":"16695","normalized":[]},{"id":"16718","type":"CID","arg1_id":"16703","arg2_id":"16697","normalized":[]},{"id":"16719","type":"CID","arg1_id":"16703","arg2_id":"16704","normalized":[]},{"id":"16720","type":"CID","arg1_id":"16703","arg2_id":"16708","normalized":[]},{"id":"16721","type":"CID","arg1_id":"16706","arg2_id":"16695","normalized":[]},{"id":"16722","type":"CID","arg1_id":"16706","arg2_id":"16697","normalized":[]},{"id":"16723","type":"CID","arg1_id":"16706","arg2_id":"16704","normalized":[]},{"id":"16724","type":"CID","arg1_id":"16706","arg2_id":"16708","normalized":[]}]}
{"id":"16725","document_id":"9812111","passages":[{"id":"16726","type":"title","text":["A randomized, placebo-controlled dose-comparison trial of haloperidol for psychosis and disruptive behaviors in Alzheimer's disease."],"offsets":[[0,132]]},{"id":"16727","type":"abstract","text":["OBJECTIVE: The goal of this study was to compare the efficacy and side effects of two doses of haloperidol and placebo in the treatment of psychosis and disruptive behaviors in patients with Alzheimer's disease. METHOD: In a 6-week random-assignment, double-blind, placebo-controlled trial (phase A), haloperidol, 2-3 mg\/day (standard dose), and haloperidol, 0.50-0.75 mg\/day (low dose), were compared in 71 outpatients with Alzheimer's disease. For the subsequent 6-week double-blind crossover phase (phase B), patients taking standard- or low-dose haloperidol were switched to placebo, and patients taking placebo were randomly assigned to standard- or low-dose haloperidol. RESULTS: For the 60 patients who completed phase A, standard-dose haloperidol was efficacious and superior to both low-dose haloperidol and placebo for scores on the Brief Psychiatric Rating Scale psychosis factor and on psychomotor agitation. Response rates according to three sets of criteria were greater with the standard dose (55%-60%) than the low dose (25%-35%) and placebo (25%-30%). The advantage of standard dose over low dose was replicated in phase B. In phase A, extrapyramidal signs tended to be greater with the standard dose than in the other two conditions, primarily because of a subgroup (20%) who developed moderate to severe signs. Low-dose haloperidol did not differ from placebo on any measure of efficacy or side effects. CONCLUSIONS: The results indicated a favorable therapeutic profile for haloperidol in doses of 2-3 mg\/day, although a subgroup developed moderate to severe extrapyramidal signs. A starting dose of 1 mg\/day with gradual, upward dose titration is recommended. The narrow therapeutic window observed with haloperidol may also apply to other neuroleptics used in Alzheimer's disease patients with psychosis and disruptive behaviors."],"offsets":[[133,1984]]}],"entities":[{"id":"16728","type":"Chemical","text":["haloperidol"],"offsets":[[58,69]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"16729","type":"Disease","text":["psychosis"],"offsets":[[74,83]],"normalized":[{"db_name":"MESH","db_id":"D011618"}]},{"id":"16730","type":"Disease","text":["disruptive behaviors"],"offsets":[[88,108]],"normalized":[{"db_name":"MESH","db_id":"D019958"}]},{"id":"16731","type":"Disease","text":["Alzheimer's disease"],"offsets":[[112,131]],"normalized":[{"db_name":"MESH","db_id":"D000544"}]},{"id":"16732","type":"Chemical","text":["haloperidol"],"offsets":[[228,239]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"16733","type":"Disease","text":["psychosis"],"offsets":[[272,281]],"normalized":[{"db_name":"MESH","db_id":"D011618"}]},{"id":"16734","type":"Disease","text":["disruptive behaviors"],"offsets":[[286,306]],"normalized":[{"db_name":"MESH","db_id":"D019958"}]},{"id":"16735","type":"Disease","text":["Alzheimer's disease"],"offsets":[[324,343]],"normalized":[{"db_name":"MESH","db_id":"D000544"}]},{"id":"16736","type":"Chemical","text":["haloperidol"],"offsets":[[434,445]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"16737","type":"Chemical","text":["haloperidol"],"offsets":[[479,490]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"16738","type":"Disease","text":["Alzheimer's disease"],"offsets":[[558,577]],"normalized":[{"db_name":"MESH","db_id":"D000544"}]},{"id":"16739","type":"Chemical","text":["haloperidol"],"offsets":[[683,694]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"16740","type":"Chemical","text":["haloperidol"],"offsets":[[797,808]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"16741","type":"Chemical","text":["haloperidol"],"offsets":[[876,887]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"16742","type":"Chemical","text":["haloperidol"],"offsets":[[934,945]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"16743","type":"Disease","text":["psychosis"],"offsets":[[1007,1016]],"normalized":[{"db_name":"MESH","db_id":"D011618"}]},{"id":"16744","type":"Disease","text":["psychomotor agitation"],"offsets":[[1031,1052]],"normalized":[{"db_name":"MESH","db_id":"D011595"}]},{"id":"16745","type":"Disease","text":["extrapyramidal signs"],"offsets":[[1286,1306]],"normalized":[{"db_name":"MESH","db_id":"D001480"}]},{"id":"16746","type":"Chemical","text":["haloperidol"],"offsets":[[1472,1483]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"16747","type":"Chemical","text":["haloperidol"],"offsets":[[1627,1638]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"16748","type":"Disease","text":["extrapyramidal signs"],"offsets":[[1712,1732]],"normalized":[{"db_name":"MESH","db_id":"D001480"}]},{"id":"16749","type":"Chemical","text":["haloperidol"],"offsets":[[1858,1869]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"16750","type":"Disease","text":["Alzheimer's disease"],"offsets":[[1915,1934]],"normalized":[{"db_name":"MESH","db_id":"D000544"}]},{"id":"16751","type":"Disease","text":["psychosis"],"offsets":[[1949,1958]],"normalized":[{"db_name":"MESH","db_id":"D011618"}]},{"id":"16752","type":"Disease","text":["disruptive behaviors"],"offsets":[[1963,1983]],"normalized":[{"db_name":"MESH","db_id":"D019958"}]}],"events":[],"coreferences":[],"relations":[{"id":"16753","type":"CID","arg1_id":"16728","arg2_id":"16745","normalized":[]},{"id":"16754","type":"CID","arg1_id":"16728","arg2_id":"16748","normalized":[]},{"id":"16755","type":"CID","arg1_id":"16732","arg2_id":"16745","normalized":[]},{"id":"16756","type":"CID","arg1_id":"16732","arg2_id":"16748","normalized":[]},{"id":"16757","type":"CID","arg1_id":"16736","arg2_id":"16745","normalized":[]},{"id":"16758","type":"CID","arg1_id":"16736","arg2_id":"16748","normalized":[]},{"id":"16759","type":"CID","arg1_id":"16737","arg2_id":"16745","normalized":[]},{"id":"16760","type":"CID","arg1_id":"16737","arg2_id":"16748","normalized":[]},{"id":"16761","type":"CID","arg1_id":"16739","arg2_id":"16745","normalized":[]},{"id":"16762","type":"CID","arg1_id":"16739","arg2_id":"16748","normalized":[]},{"id":"16763","type":"CID","arg1_id":"16740","arg2_id":"16745","normalized":[]},{"id":"16764","type":"CID","arg1_id":"16740","arg2_id":"16748","normalized":[]},{"id":"16765","type":"CID","arg1_id":"16741","arg2_id":"16745","normalized":[]},{"id":"16766","type":"CID","arg1_id":"16741","arg2_id":"16748","normalized":[]},{"id":"16767","type":"CID","arg1_id":"16742","arg2_id":"16745","normalized":[]},{"id":"16768","type":"CID","arg1_id":"16742","arg2_id":"16748","normalized":[]},{"id":"16769","type":"CID","arg1_id":"16746","arg2_id":"16745","normalized":[]},{"id":"16770","type":"CID","arg1_id":"16746","arg2_id":"16748","normalized":[]},{"id":"16771","type":"CID","arg1_id":"16747","arg2_id":"16745","normalized":[]},{"id":"16772","type":"CID","arg1_id":"16747","arg2_id":"16748","normalized":[]},{"id":"16773","type":"CID","arg1_id":"16749","arg2_id":"16745","normalized":[]},{"id":"16774","type":"CID","arg1_id":"16749","arg2_id":"16748","normalized":[]}]}
{"id":"16775","document_id":"15572383","passages":[{"id":"16776","type":"title","text":["Individual differences in renal ACE activity in healthy rats predict susceptibility to adriamycin-induced renal damage."],"offsets":[[0,119]]},{"id":"16777","type":"abstract","text":["BACKGROUND: In man, differences in angiotensin-converting enzyme (ACE) levels, related to ACE (I\/D) genotype, are associated with renal prognosis. This raises the hypothesis that individual differences in renal ACE activity are involved in renal susceptibility to inflicted damage. Therefore, we studied the predictive effect of renal ACE activity for the severity of renal damage induced by a single injection of adriamycin in rats. METHODS: Renal ACE activity (Hip-His-Leu cleavage by cortical homogenates) was determined by renal biopsy in 27 adult male Wistar rats. After 1 week of recovery, proteinuria was induced by adriamycin [1.5 mg\/kg intravenously (i.v.) n = 18; controls, saline i.v. n = 9]. Proteinuria was measured every 2 weeks. After 12 weeks, rats were sacrificed and their kidneys harvested. RESULTS: As anticipated, adriamycin elicited nephrotic range proteinuria, renal interstitial damage and mild focal glomerulosclerosis. Baseline renal ACE positively correlated with the relative rise in proteinuria after adriamycin (r = 0.62, P<0.01), renal interstitial alpha-smooth muscle actin (r = 0.49, P<0.05), interstitial macrophage influx (r = 0.56, P<0.05), interstitial collagen III (r = 0.53, P<0.05), glomerular alpha-smooth muscle actin (r = 0.74, P<0.01) and glomerular desmin (r = 0.48, P<0.05). Baseline renal ACE did not correlate with focal glomerulosclerosis (r = 0.22, NS). In controls, no predictive values for renal parameters were observed. CONCLUSION: Individual differences in renal ACE activity predict the severity of adriamycin-induced renal damage in this outbred rat strain. This supports the assumption that differences in renal ACE activity predispose to a less favourable course of renal damage."],"offsets":[[120,1858]]}],"entities":[{"id":"16778","type":"Chemical","text":["adriamycin"],"offsets":[[87,97]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"16779","type":"Disease","text":["renal damage"],"offsets":[[106,118]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"16780","type":"Chemical","text":["angiotensin"],"offsets":[[155,166]],"normalized":[{"db_name":"MESH","db_id":"D000809"}]},{"id":"16781","type":"Disease","text":["renal damage"],"offsets":[[488,500]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"16782","type":"Chemical","text":["adriamycin"],"offsets":[[534,544]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"16783","type":"Chemical","text":["Hip-His-Leu"],"offsets":[[583,594]],"normalized":[{"db_name":"MESH","db_id":"C010980"}]},{"id":"16784","type":"Disease","text":["proteinuria"],"offsets":[[716,727]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]},{"id":"16785","type":"Chemical","text":["adriamycin"],"offsets":[[743,753]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"16786","type":"Disease","text":["Proteinuria"],"offsets":[[824,835]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]},{"id":"16787","type":"Chemical","text":["adriamycin"],"offsets":[[955,965]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"16788","type":"Disease","text":["nephrotic"],"offsets":[[975,984]],"normalized":[{"db_name":"MESH","db_id":"D009404"}]},{"id":"16789","type":"Disease","text":["proteinuria"],"offsets":[[991,1002]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]},{"id":"16790","type":"Disease","text":["renal interstitial damage"],"offsets":[[1004,1029]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"16791","type":"Disease","text":["focal glomerulosclerosis"],"offsets":[[1039,1063]],"normalized":[{"db_name":"MESH","db_id":"D005923"}]},{"id":"16792","type":"Disease","text":["proteinuria"],"offsets":[[1132,1143]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]},{"id":"16793","type":"Chemical","text":["adriamycin"],"offsets":[[1150,1160]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"16794","type":"Disease","text":["focal glomerulosclerosis"],"offsets":[[1483,1507]],"normalized":[{"db_name":"MESH","db_id":"D005923"}]},{"id":"16795","type":"Chemical","text":["adriamycin"],"offsets":[[1675,1685]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"16796","type":"Disease","text":["renal damage"],"offsets":[[1694,1706]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"16797","type":"Disease","text":["renal damage"],"offsets":[[1845,1857]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]}],"events":[],"coreferences":[],"relations":[{"id":"16798","type":"CID","arg1_id":"16778","arg2_id":"16784","normalized":[]},{"id":"16799","type":"CID","arg1_id":"16778","arg2_id":"16786","normalized":[]},{"id":"16800","type":"CID","arg1_id":"16778","arg2_id":"16789","normalized":[]},{"id":"16801","type":"CID","arg1_id":"16778","arg2_id":"16792","normalized":[]},{"id":"16802","type":"CID","arg1_id":"16782","arg2_id":"16784","normalized":[]},{"id":"16803","type":"CID","arg1_id":"16782","arg2_id":"16786","normalized":[]},{"id":"16804","type":"CID","arg1_id":"16782","arg2_id":"16789","normalized":[]},{"id":"16805","type":"CID","arg1_id":"16782","arg2_id":"16792","normalized":[]},{"id":"16806","type":"CID","arg1_id":"16785","arg2_id":"16784","normalized":[]},{"id":"16807","type":"CID","arg1_id":"16785","arg2_id":"16786","normalized":[]},{"id":"16808","type":"CID","arg1_id":"16785","arg2_id":"16789","normalized":[]},{"id":"16809","type":"CID","arg1_id":"16785","arg2_id":"16792","normalized":[]},{"id":"16810","type":"CID","arg1_id":"16787","arg2_id":"16784","normalized":[]},{"id":"16811","type":"CID","arg1_id":"16787","arg2_id":"16786","normalized":[]},{"id":"16812","type":"CID","arg1_id":"16787","arg2_id":"16789","normalized":[]},{"id":"16813","type":"CID","arg1_id":"16787","arg2_id":"16792","normalized":[]},{"id":"16814","type":"CID","arg1_id":"16793","arg2_id":"16784","normalized":[]},{"id":"16815","type":"CID","arg1_id":"16793","arg2_id":"16786","normalized":[]},{"id":"16816","type":"CID","arg1_id":"16793","arg2_id":"16789","normalized":[]},{"id":"16817","type":"CID","arg1_id":"16793","arg2_id":"16792","normalized":[]},{"id":"16818","type":"CID","arg1_id":"16795","arg2_id":"16784","normalized":[]},{"id":"16819","type":"CID","arg1_id":"16795","arg2_id":"16786","normalized":[]},{"id":"16820","type":"CID","arg1_id":"16795","arg2_id":"16789","normalized":[]},{"id":"16821","type":"CID","arg1_id":"16795","arg2_id":"16792","normalized":[]}]}
{"id":"16822","document_id":"7420681","passages":[{"id":"16823","type":"title","text":["Clinical nephrotoxicity of tobramycin and gentamicin. A prospective study."],"offsets":[[0,74]]},{"id":"16824","type":"abstract","text":["Nearly 3.2 million people in this country receive aminoglycoside antibiotics annually. Gentamicin sulfate and tobramycin sulfate continue to demonstrate ototoxicity and nephrotoxicity in both animal and clinical studies. In this study, 62 patients with confirmed initial normal renal function and treated with 2 to 5 mg\/kg\/day of gentamicin sulfate or tobramycin sulfate for a minimum of seven days were followed up prospectively for the development of aminoglycoside-related renal failure, defined as at least a one-third reduction in renal function. In these 62 patients, no other causes for renal failure could be identified. Five of 33 (15%) of the tobramycin-treated patients and 16 of 29 (55.2%) of the gentamicin-treated patients had renal failure. Thus, gentamicin was associated with renal failure more than three times as often as was tobramycin."],"offsets":[[75,931]]}],"entities":[{"id":"16825","type":"Disease","text":["nephrotoxicity"],"offsets":[[9,23]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"16826","type":"Chemical","text":["tobramycin"],"offsets":[[27,37]],"normalized":[{"db_name":"MESH","db_id":"D014031"}]},{"id":"16827","type":"Chemical","text":["gentamicin"],"offsets":[[42,52]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"16828","type":"Chemical","text":["aminoglycoside"],"offsets":[[125,139]],"normalized":[{"db_name":"MESH","db_id":"D000617"}]},{"id":"16829","type":"Chemical","text":["Gentamicin sulfate"],"offsets":[[162,180]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"16830","type":"Chemical","text":["tobramycin sulfate"],"offsets":[[185,203]],"normalized":[{"db_name":"MESH","db_id":"D014031"}]},{"id":"16831","type":"Disease","text":["ototoxicity"],"offsets":[[228,239]],"normalized":[{"db_name":"MESH","db_id":"D006311"}]},{"id":"16832","type":"Disease","text":["nephrotoxicity"],"offsets":[[244,258]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"16833","type":"Chemical","text":["gentamicin sulfate"],"offsets":[[405,423]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"16834","type":"Chemical","text":["tobramycin sulfate"],"offsets":[[427,445]],"normalized":[{"db_name":"MESH","db_id":"D014031"}]},{"id":"16835","type":"Chemical","text":["aminoglycoside"],"offsets":[[528,542]],"normalized":[{"db_name":"MESH","db_id":"D000617"}]},{"id":"16836","type":"Disease","text":["renal failure"],"offsets":[[551,564]],"normalized":[{"db_name":"MESH","db_id":"D051437"}]},{"id":"16837","type":"Disease","text":["renal failure"],"offsets":[[669,682]],"normalized":[{"db_name":"MESH","db_id":"D051437"}]},{"id":"16838","type":"Chemical","text":["tobramycin"],"offsets":[[728,738]],"normalized":[{"db_name":"MESH","db_id":"D014031"}]},{"id":"16839","type":"Chemical","text":["gentamicin"],"offsets":[[784,794]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"16840","type":"Disease","text":["renal failure"],"offsets":[[816,829]],"normalized":[{"db_name":"MESH","db_id":"D051437"}]},{"id":"16841","type":"Chemical","text":["gentamicin"],"offsets":[[837,847]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"16842","type":"Disease","text":["renal failure"],"offsets":[[868,881]],"normalized":[{"db_name":"MESH","db_id":"D051437"}]},{"id":"16843","type":"Chemical","text":["tobramycin"],"offsets":[[920,930]],"normalized":[{"db_name":"MESH","db_id":"D014031"}]}],"events":[],"coreferences":[],"relations":[{"id":"16844","type":"CID","arg1_id":"16827","arg2_id":"16836","normalized":[]},{"id":"16845","type":"CID","arg1_id":"16827","arg2_id":"16837","normalized":[]},{"id":"16846","type":"CID","arg1_id":"16827","arg2_id":"16840","normalized":[]},{"id":"16847","type":"CID","arg1_id":"16827","arg2_id":"16842","normalized":[]},{"id":"16848","type":"CID","arg1_id":"16829","arg2_id":"16836","normalized":[]},{"id":"16849","type":"CID","arg1_id":"16829","arg2_id":"16837","normalized":[]},{"id":"16850","type":"CID","arg1_id":"16829","arg2_id":"16840","normalized":[]},{"id":"16851","type":"CID","arg1_id":"16829","arg2_id":"16842","normalized":[]},{"id":"16852","type":"CID","arg1_id":"16833","arg2_id":"16836","normalized":[]},{"id":"16853","type":"CID","arg1_id":"16833","arg2_id":"16837","normalized":[]},{"id":"16854","type":"CID","arg1_id":"16833","arg2_id":"16840","normalized":[]},{"id":"16855","type":"CID","arg1_id":"16833","arg2_id":"16842","normalized":[]},{"id":"16856","type":"CID","arg1_id":"16839","arg2_id":"16836","normalized":[]},{"id":"16857","type":"CID","arg1_id":"16839","arg2_id":"16837","normalized":[]},{"id":"16858","type":"CID","arg1_id":"16839","arg2_id":"16840","normalized":[]},{"id":"16859","type":"CID","arg1_id":"16839","arg2_id":"16842","normalized":[]},{"id":"16860","type":"CID","arg1_id":"16841","arg2_id":"16836","normalized":[]},{"id":"16861","type":"CID","arg1_id":"16841","arg2_id":"16837","normalized":[]},{"id":"16862","type":"CID","arg1_id":"16841","arg2_id":"16840","normalized":[]},{"id":"16863","type":"CID","arg1_id":"16841","arg2_id":"16842","normalized":[]},{"id":"16864","type":"CID","arg1_id":"16826","arg2_id":"16836","normalized":[]},{"id":"16865","type":"CID","arg1_id":"16826","arg2_id":"16837","normalized":[]},{"id":"16866","type":"CID","arg1_id":"16826","arg2_id":"16840","normalized":[]},{"id":"16867","type":"CID","arg1_id":"16826","arg2_id":"16842","normalized":[]},{"id":"16868","type":"CID","arg1_id":"16830","arg2_id":"16836","normalized":[]},{"id":"16869","type":"CID","arg1_id":"16830","arg2_id":"16837","normalized":[]},{"id":"16870","type":"CID","arg1_id":"16830","arg2_id":"16840","normalized":[]},{"id":"16871","type":"CID","arg1_id":"16830","arg2_id":"16842","normalized":[]},{"id":"16872","type":"CID","arg1_id":"16834","arg2_id":"16836","normalized":[]},{"id":"16873","type":"CID","arg1_id":"16834","arg2_id":"16837","normalized":[]},{"id":"16874","type":"CID","arg1_id":"16834","arg2_id":"16840","normalized":[]},{"id":"16875","type":"CID","arg1_id":"16834","arg2_id":"16842","normalized":[]},{"id":"16876","type":"CID","arg1_id":"16838","arg2_id":"16836","normalized":[]},{"id":"16877","type":"CID","arg1_id":"16838","arg2_id":"16837","normalized":[]},{"id":"16878","type":"CID","arg1_id":"16838","arg2_id":"16840","normalized":[]},{"id":"16879","type":"CID","arg1_id":"16838","arg2_id":"16842","normalized":[]},{"id":"16880","type":"CID","arg1_id":"16843","arg2_id":"16836","normalized":[]},{"id":"16881","type":"CID","arg1_id":"16843","arg2_id":"16837","normalized":[]},{"id":"16882","type":"CID","arg1_id":"16843","arg2_id":"16840","normalized":[]},{"id":"16883","type":"CID","arg1_id":"16843","arg2_id":"16842","normalized":[]}]}
{"id":"16884","document_id":"12907309","passages":[{"id":"16885","type":"title","text":["Neuroprotective action of MPEP, a selective mGluR5 antagonist, in methamphetamine-induced dopaminergic neurotoxicity is associated with a decrease in dopamine outflow and inhibition of hyperthermia in rats."],"offsets":[[0,206]]},{"id":"16886","type":"abstract","text":["The aim of this study was to examine the role of metabotropic glutamate receptor 5 (mGluR5) in the toxic action of methamphetamine on dopaminergic neurones in rats. Methamphetamine (10 mg\/kg sc), administered five times, reduced the levels of dopamine and its metabolites in striatal tissue when measured 72 h after the last injection. A selective antagonist of mGluR5, 2-methyl-6-(phenylethynyl)pyridine (MPEP; 5 mg\/kg ip), when administered five times immediately before each methamphetamine injection reversed the above-mentioned methamphetamine effects. A single MPEP (5 mg\/kg ip) injection reduced the basal extracellular dopamine level in the striatum, as well as dopamine release stimulated either by methamphetamine (10 mg\/kg sc) or by intrastriatally administered veratridine (100 microM). Moreover, it transiently diminished the methamphetamine (10 mg\/kg sc)-induced hyperthermia and reduced basal body temperature. MPEP administered into the striatum at high concentrations (500 microM) increased extracellular dopamine levels, while lower concentrations (50-100 microM) were devoid of any effect. The results of this study suggest that the blockade of mGluR5 by MPEP may protect dopaminergic neurones against methamphetamine-induced toxicity. Neuroprotection rendered by MPEP may be associated with the reduction of the methamphetamine-induced dopamine efflux in the striatum due to the blockade of extrastriatal mGluR5, and with a decrease in hyperthermia."],"offsets":[[207,1676]]}],"entities":[{"id":"16887","type":"Chemical","text":["MPEP"],"offsets":[[26,30]],"normalized":[{"db_name":"MESH","db_id":"C121465"}]},{"id":"16888","type":"Chemical","text":["methamphetamine"],"offsets":[[66,81]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"16889","type":"Disease","text":["neurotoxicity"],"offsets":[[103,116]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"16890","type":"Chemical","text":["dopamine"],"offsets":[[150,158]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"16891","type":"Disease","text":["hyperthermia"],"offsets":[[185,197]],"normalized":[{"db_name":"MESH","db_id":"D005334"}]},{"id":"16892","type":"Chemical","text":["glutamate"],"offsets":[[269,278]],"normalized":[{"db_name":"MESH","db_id":"D018698"}]},{"id":"16893","type":"Chemical","text":["methamphetamine"],"offsets":[[322,337]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"16894","type":"Chemical","text":["Methamphetamine"],"offsets":[[372,387]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"16895","type":"Chemical","text":["dopamine"],"offsets":[[450,458]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"16896","type":"Chemical","text":["2-methyl-6-(phenylethynyl)pyridine"],"offsets":[[577,611]],"normalized":[{"db_name":"MESH","db_id":"C121465"}]},{"id":"16897","type":"Chemical","text":["MPEP"],"offsets":[[613,617]],"normalized":[{"db_name":"MESH","db_id":"C121465"}]},{"id":"16898","type":"Chemical","text":["methamphetamine"],"offsets":[[685,700]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"16899","type":"Chemical","text":["methamphetamine"],"offsets":[[740,755]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"16900","type":"Chemical","text":["MPEP"],"offsets":[[774,778]],"normalized":[{"db_name":"MESH","db_id":"C121465"}]},{"id":"16901","type":"Chemical","text":["dopamine"],"offsets":[[834,842]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"16902","type":"Chemical","text":["dopamine"],"offsets":[[877,885]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"16903","type":"Chemical","text":["methamphetamine"],"offsets":[[915,930]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"16904","type":"Chemical","text":["veratridine"],"offsets":[[980,991]],"normalized":[{"db_name":"MESH","db_id":"D014701"}]},{"id":"16905","type":"Chemical","text":["methamphetamine"],"offsets":[[1046,1061]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"16906","type":"Disease","text":["hyperthermia"],"offsets":[[1084,1096]],"normalized":[{"db_name":"MESH","db_id":"D005334"}]},{"id":"16907","type":"Chemical","text":["MPEP"],"offsets":[[1133,1137]],"normalized":[{"db_name":"MESH","db_id":"C121465"}]},{"id":"16908","type":"Chemical","text":["dopamine"],"offsets":[[1229,1237]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"16909","type":"Chemical","text":["MPEP"],"offsets":[[1381,1385]],"normalized":[{"db_name":"MESH","db_id":"C121465"}]},{"id":"16910","type":"Chemical","text":["methamphetamine"],"offsets":[[1428,1443]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"16911","type":"Disease","text":["toxicity"],"offsets":[[1452,1460]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"16912","type":"Chemical","text":["MPEP"],"offsets":[[1490,1494]],"normalized":[{"db_name":"MESH","db_id":"C121465"}]},{"id":"16913","type":"Chemical","text":["methamphetamine"],"offsets":[[1539,1554]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"16914","type":"Chemical","text":["dopamine"],"offsets":[[1563,1571]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"16915","type":"Disease","text":["hyperthermia"],"offsets":[[1663,1675]],"normalized":[{"db_name":"MESH","db_id":"D005334"}]}],"events":[],"coreferences":[],"relations":[{"id":"16916","type":"CID","arg1_id":"16888","arg2_id":"16891","normalized":[]},{"id":"16917","type":"CID","arg1_id":"16888","arg2_id":"16906","normalized":[]},{"id":"16918","type":"CID","arg1_id":"16888","arg2_id":"16915","normalized":[]},{"id":"16919","type":"CID","arg1_id":"16893","arg2_id":"16891","normalized":[]},{"id":"16920","type":"CID","arg1_id":"16893","arg2_id":"16906","normalized":[]},{"id":"16921","type":"CID","arg1_id":"16893","arg2_id":"16915","normalized":[]},{"id":"16922","type":"CID","arg1_id":"16894","arg2_id":"16891","normalized":[]},{"id":"16923","type":"CID","arg1_id":"16894","arg2_id":"16906","normalized":[]},{"id":"16924","type":"CID","arg1_id":"16894","arg2_id":"16915","normalized":[]},{"id":"16925","type":"CID","arg1_id":"16898","arg2_id":"16891","normalized":[]},{"id":"16926","type":"CID","arg1_id":"16898","arg2_id":"16906","normalized":[]},{"id":"16927","type":"CID","arg1_id":"16898","arg2_id":"16915","normalized":[]},{"id":"16928","type":"CID","arg1_id":"16899","arg2_id":"16891","normalized":[]},{"id":"16929","type":"CID","arg1_id":"16899","arg2_id":"16906","normalized":[]},{"id":"16930","type":"CID","arg1_id":"16899","arg2_id":"16915","normalized":[]},{"id":"16931","type":"CID","arg1_id":"16903","arg2_id":"16891","normalized":[]},{"id":"16932","type":"CID","arg1_id":"16903","arg2_id":"16906","normalized":[]},{"id":"16933","type":"CID","arg1_id":"16903","arg2_id":"16915","normalized":[]},{"id":"16934","type":"CID","arg1_id":"16905","arg2_id":"16891","normalized":[]},{"id":"16935","type":"CID","arg1_id":"16905","arg2_id":"16906","normalized":[]},{"id":"16936","type":"CID","arg1_id":"16905","arg2_id":"16915","normalized":[]},{"id":"16937","type":"CID","arg1_id":"16910","arg2_id":"16891","normalized":[]},{"id":"16938","type":"CID","arg1_id":"16910","arg2_id":"16906","normalized":[]},{"id":"16939","type":"CID","arg1_id":"16910","arg2_id":"16915","normalized":[]},{"id":"16940","type":"CID","arg1_id":"16913","arg2_id":"16891","normalized":[]},{"id":"16941","type":"CID","arg1_id":"16913","arg2_id":"16906","normalized":[]},{"id":"16942","type":"CID","arg1_id":"16913","arg2_id":"16915","normalized":[]}]}
{"id":"16943","document_id":"16680561","passages":[{"id":"16944","type":"title","text":["Pharmacokinetics of desipramine HCl when administered with cinacalcet HCl."],"offsets":[[0,74]]},{"id":"16945","type":"abstract","text":["OBJECTIVE: In vitro work has demonstrated that cinacalcet is a strong inhibitor of cytochrome P450 isoenzyme (CYP) 2D6. The purpose of this study was to evaluate the effect of cinacalcet on CYP2D6 activity, using desipramine as a probe substrate, in healthy subjects. METHODS: Seventeen subjects who were genotyped as CYP2D6 extensive metabolizers were enrolled in this randomized, open-label, crossover study to receive a single oral dose of desipramine (50 mg) on two separate occasions, once alone and once after multiple doses of cinacalcet (90 mg for 7 days). Blood samples were obtained predose and up to 72 h postdose. RESULTS: Fourteen subjects completed both treatment arms. Relative to desipramine alone, mean AUC and C(max) of desipramine increased 3.6- and 1.8-fold when coadministered with cinacalcet. The t (1\/2,z) of desipramine was longer when desipramine was coadministered with cinacalcet (21.0 versus 43.3 hs). The t (max) was similar between the regimens. Fewer subjects reported adverse events following treatment with desipramine alone than when receiving desipramine with cinacalcet (33 versus 86%), the most frequent of which (nausea and headache) have been reported for patients treated with either desipramine or cinacalcet. CONCLUSION: This study demonstrates that cinacalcet is a strong inhibitor of CYP2D6. These data suggest that during concomitant treatment with cinacalcet, dose adjustment may be necessary for drugs that demonstrate a narrow therapeutic index and are metabolized by CYP2D6."],"offsets":[[75,1598]]}],"entities":[{"id":"16946","type":"Chemical","text":["desipramine HCl"],"offsets":[[20,35]],"normalized":[{"db_name":"MESH","db_id":"D003891"}]},{"id":"16947","type":"Chemical","text":["cinacalcet HCl"],"offsets":[[59,73]],"normalized":[{"db_name":"MESH","db_id":"C476217"}]},{"id":"16948","type":"Chemical","text":["cinacalcet"],"offsets":[[122,132]],"normalized":[{"db_name":"MESH","db_id":"C476217"}]},{"id":"16949","type":"Chemical","text":["cinacalcet"],"offsets":[[251,261]],"normalized":[{"db_name":"MESH","db_id":"C476217"}]},{"id":"16950","type":"Chemical","text":["desipramine"],"offsets":[[288,299]],"normalized":[{"db_name":"MESH","db_id":"D003891"}]},{"id":"16951","type":"Chemical","text":["desipramine"],"offsets":[[518,529]],"normalized":[{"db_name":"MESH","db_id":"D003891"}]},{"id":"16952","type":"Chemical","text":["cinacalcet"],"offsets":[[609,619]],"normalized":[{"db_name":"MESH","db_id":"C476217"}]},{"id":"16953","type":"Chemical","text":["desipramine"],"offsets":[[771,782]],"normalized":[{"db_name":"MESH","db_id":"D003891"}]},{"id":"16954","type":"Chemical","text":["desipramine"],"offsets":[[813,824]],"normalized":[{"db_name":"MESH","db_id":"D003891"}]},{"id":"16955","type":"Chemical","text":["cinacalcet"],"offsets":[[878,888]],"normalized":[{"db_name":"MESH","db_id":"C476217"}]},{"id":"16956","type":"Chemical","text":["desipramine"],"offsets":[[907,918]],"normalized":[{"db_name":"MESH","db_id":"D003891"}]},{"id":"16957","type":"Chemical","text":["desipramine"],"offsets":[[935,946]],"normalized":[{"db_name":"MESH","db_id":"D003891"}]},{"id":"16958","type":"Chemical","text":["cinacalcet"],"offsets":[[971,981]],"normalized":[{"db_name":"MESH","db_id":"C476217"}]},{"id":"16959","type":"Chemical","text":["desipramine"],"offsets":[[1115,1126]],"normalized":[{"db_name":"MESH","db_id":"D003891"}]},{"id":"16960","type":"Chemical","text":["desipramine"],"offsets":[[1153,1164]],"normalized":[{"db_name":"MESH","db_id":"D003891"}]},{"id":"16961","type":"Chemical","text":["cinacalcet"],"offsets":[[1170,1180]],"normalized":[{"db_name":"MESH","db_id":"C476217"}]},{"id":"16962","type":"Disease","text":["nausea"],"offsets":[[1226,1232]],"normalized":[{"db_name":"MESH","db_id":"D009325"}]},{"id":"16963","type":"Disease","text":["headache"],"offsets":[[1237,1245]],"normalized":[{"db_name":"MESH","db_id":"D006261"}]},{"id":"16964","type":"Chemical","text":["desipramine"],"offsets":[[1299,1310]],"normalized":[{"db_name":"MESH","db_id":"D003891"}]},{"id":"16965","type":"Chemical","text":["cinacalcet"],"offsets":[[1314,1324]],"normalized":[{"db_name":"MESH","db_id":"C476217"}]},{"id":"16966","type":"Chemical","text":["cinacalcet"],"offsets":[[1367,1377]],"normalized":[{"db_name":"MESH","db_id":"C476217"}]},{"id":"16967","type":"Chemical","text":["cinacalcet"],"offsets":[[1469,1479]],"normalized":[{"db_name":"MESH","db_id":"C476217"}]}],"events":[],"coreferences":[],"relations":[{"id":"16968","type":"CID","arg1_id":"16946","arg2_id":"16962","normalized":[]},{"id":"16969","type":"CID","arg1_id":"16950","arg2_id":"16962","normalized":[]},{"id":"16970","type":"CID","arg1_id":"16951","arg2_id":"16962","normalized":[]},{"id":"16971","type":"CID","arg1_id":"16953","arg2_id":"16962","normalized":[]},{"id":"16972","type":"CID","arg1_id":"16954","arg2_id":"16962","normalized":[]},{"id":"16973","type":"CID","arg1_id":"16956","arg2_id":"16962","normalized":[]},{"id":"16974","type":"CID","arg1_id":"16957","arg2_id":"16962","normalized":[]},{"id":"16975","type":"CID","arg1_id":"16959","arg2_id":"16962","normalized":[]},{"id":"16976","type":"CID","arg1_id":"16960","arg2_id":"16962","normalized":[]},{"id":"16977","type":"CID","arg1_id":"16964","arg2_id":"16962","normalized":[]},{"id":"16978","type":"CID","arg1_id":"16947","arg2_id":"16963","normalized":[]},{"id":"16979","type":"CID","arg1_id":"16948","arg2_id":"16963","normalized":[]},{"id":"16980","type":"CID","arg1_id":"16949","arg2_id":"16963","normalized":[]},{"id":"16981","type":"CID","arg1_id":"16952","arg2_id":"16963","normalized":[]},{"id":"16982","type":"CID","arg1_id":"16955","arg2_id":"16963","normalized":[]},{"id":"16983","type":"CID","arg1_id":"16958","arg2_id":"16963","normalized":[]},{"id":"16984","type":"CID","arg1_id":"16961","arg2_id":"16963","normalized":[]},{"id":"16985","type":"CID","arg1_id":"16965","arg2_id":"16963","normalized":[]},{"id":"16986","type":"CID","arg1_id":"16966","arg2_id":"16963","normalized":[]},{"id":"16987","type":"CID","arg1_id":"16967","arg2_id":"16963","normalized":[]},{"id":"16988","type":"CID","arg1_id":"16946","arg2_id":"16963","normalized":[]},{"id":"16989","type":"CID","arg1_id":"16950","arg2_id":"16963","normalized":[]},{"id":"16990","type":"CID","arg1_id":"16951","arg2_id":"16963","normalized":[]},{"id":"16991","type":"CID","arg1_id":"16953","arg2_id":"16963","normalized":[]},{"id":"16992","type":"CID","arg1_id":"16954","arg2_id":"16963","normalized":[]},{"id":"16993","type":"CID","arg1_id":"16956","arg2_id":"16963","normalized":[]},{"id":"16994","type":"CID","arg1_id":"16957","arg2_id":"16963","normalized":[]},{"id":"16995","type":"CID","arg1_id":"16959","arg2_id":"16963","normalized":[]},{"id":"16996","type":"CID","arg1_id":"16960","arg2_id":"16963","normalized":[]},{"id":"16997","type":"CID","arg1_id":"16964","arg2_id":"16963","normalized":[]},{"id":"16998","type":"CID","arg1_id":"16947","arg2_id":"16962","normalized":[]},{"id":"16999","type":"CID","arg1_id":"16948","arg2_id":"16962","normalized":[]},{"id":"17000","type":"CID","arg1_id":"16949","arg2_id":"16962","normalized":[]},{"id":"17001","type":"CID","arg1_id":"16952","arg2_id":"16962","normalized":[]},{"id":"17002","type":"CID","arg1_id":"16955","arg2_id":"16962","normalized":[]},{"id":"17003","type":"CID","arg1_id":"16958","arg2_id":"16962","normalized":[]},{"id":"17004","type":"CID","arg1_id":"16961","arg2_id":"16962","normalized":[]},{"id":"17005","type":"CID","arg1_id":"16965","arg2_id":"16962","normalized":[]},{"id":"17006","type":"CID","arg1_id":"16966","arg2_id":"16962","normalized":[]},{"id":"17007","type":"CID","arg1_id":"16967","arg2_id":"16962","normalized":[]}]}
{"id":"17008","document_id":"17532790","passages":[{"id":"17009","type":"title","text":["Proteomic analysis of striatal proteins in the rat model of L-DOPA-induced dyskinesia."],"offsets":[[0,86]]},{"id":"17010","type":"abstract","text":["L-DOPA-induced dyskinesia (LID) is among the motor complications that arise in Parkinson's disease (PD) patients after a prolonged treatment with L-DOPA. To this day, transcriptome analysis has been performed in a rat model of LID [Neurobiol. Dis., 17 (2004), 219] but information regarding the proteome is still lacking. In the present study, we investigated the changes occurring at the protein level in striatal samples obtained from the unilaterally 6-hydroxydopamine-lesion rat model of PD treated with saline, L-DOPA or bromocriptine using two-dimensional difference gel electrophoresis and mass spectrometry (MS). Rats treated with L-DOPA were allocated to two groups based on the presence or absence of LID. Among the 2000 spots compared for statistical difference, 67 spots were significantly changed in abundance and identified using matrix-assisted laser desorption\/ionization time-of-flight MS, atmospheric pressure matrix-assisted laser desorption\/ionization and HPLC coupled tandem MS (LC\/MS\/MS). Out of these 67 proteins, LID significantly changed the expression level of five proteins: alphabeta-crystalin, gamma-enolase, guanidoacetate methyltransferase, vinculin, and proteasome alpha-2 subunit. Complementary techniques such as western immunoblotting and immunohistochemistry were performed to investigate the validity of the data obtained using the proteomic approach. In conclusion, this study provides new insights into the protein changes occurring in LID."],"offsets":[[87,1566]]}],"entities":[{"id":"17011","type":"Chemical","text":["L-DOPA"],"offsets":[[60,66]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"17012","type":"Disease","text":["dyskinesia"],"offsets":[[75,85]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"17013","type":"Chemical","text":["L-DOPA"],"offsets":[[87,93]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"17014","type":"Disease","text":["dyskinesia"],"offsets":[[102,112]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"17015","type":"Disease","text":["LID"],"offsets":[[114,117]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"17016","type":"Disease","text":["Parkinson's disease"],"offsets":[[166,185]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"17017","type":"Disease","text":["PD"],"offsets":[[187,189]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"17018","type":"Chemical","text":["L-DOPA"],"offsets":[[233,239]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"17019","type":"Disease","text":["LID"],"offsets":[[314,317]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"17020","type":"Chemical","text":["6-hydroxydopamine"],"offsets":[[541,558]],"normalized":[{"db_name":"MESH","db_id":"D016627"}]},{"id":"17021","type":"Disease","text":["PD"],"offsets":[[579,581]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"17022","type":"Chemical","text":["L-DOPA"],"offsets":[[603,609]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"17023","type":"Chemical","text":["bromocriptine"],"offsets":[[613,626]],"normalized":[{"db_name":"MESH","db_id":"D001971"}]},{"id":"17024","type":"Chemical","text":["L-DOPA"],"offsets":[[726,732]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"17025","type":"Disease","text":["LID"],"offsets":[[798,801]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"17026","type":"Disease","text":["LID"],"offsets":[[1124,1127]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"17027","type":"Disease","text":["LID"],"offsets":[[1562,1565]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]}],"events":[],"coreferences":[],"relations":[{"id":"17028","type":"CID","arg1_id":"17011","arg2_id":"17012","normalized":[]},{"id":"17029","type":"CID","arg1_id":"17011","arg2_id":"17014","normalized":[]},{"id":"17030","type":"CID","arg1_id":"17011","arg2_id":"17015","normalized":[]},{"id":"17031","type":"CID","arg1_id":"17011","arg2_id":"17019","normalized":[]},{"id":"17032","type":"CID","arg1_id":"17011","arg2_id":"17025","normalized":[]},{"id":"17033","type":"CID","arg1_id":"17011","arg2_id":"17026","normalized":[]},{"id":"17034","type":"CID","arg1_id":"17011","arg2_id":"17027","normalized":[]},{"id":"17035","type":"CID","arg1_id":"17013","arg2_id":"17012","normalized":[]},{"id":"17036","type":"CID","arg1_id":"17013","arg2_id":"17014","normalized":[]},{"id":"17037","type":"CID","arg1_id":"17013","arg2_id":"17015","normalized":[]},{"id":"17038","type":"CID","arg1_id":"17013","arg2_id":"17019","normalized":[]},{"id":"17039","type":"CID","arg1_id":"17013","arg2_id":"17025","normalized":[]},{"id":"17040","type":"CID","arg1_id":"17013","arg2_id":"17026","normalized":[]},{"id":"17041","type":"CID","arg1_id":"17013","arg2_id":"17027","normalized":[]},{"id":"17042","type":"CID","arg1_id":"17018","arg2_id":"17012","normalized":[]},{"id":"17043","type":"CID","arg1_id":"17018","arg2_id":"17014","normalized":[]},{"id":"17044","type":"CID","arg1_id":"17018","arg2_id":"17015","normalized":[]},{"id":"17045","type":"CID","arg1_id":"17018","arg2_id":"17019","normalized":[]},{"id":"17046","type":"CID","arg1_id":"17018","arg2_id":"17025","normalized":[]},{"id":"17047","type":"CID","arg1_id":"17018","arg2_id":"17026","normalized":[]},{"id":"17048","type":"CID","arg1_id":"17018","arg2_id":"17027","normalized":[]},{"id":"17049","type":"CID","arg1_id":"17022","arg2_id":"17012","normalized":[]},{"id":"17050","type":"CID","arg1_id":"17022","arg2_id":"17014","normalized":[]},{"id":"17051","type":"CID","arg1_id":"17022","arg2_id":"17015","normalized":[]},{"id":"17052","type":"CID","arg1_id":"17022","arg2_id":"17019","normalized":[]},{"id":"17053","type":"CID","arg1_id":"17022","arg2_id":"17025","normalized":[]},{"id":"17054","type":"CID","arg1_id":"17022","arg2_id":"17026","normalized":[]},{"id":"17055","type":"CID","arg1_id":"17022","arg2_id":"17027","normalized":[]},{"id":"17056","type":"CID","arg1_id":"17024","arg2_id":"17012","normalized":[]},{"id":"17057","type":"CID","arg1_id":"17024","arg2_id":"17014","normalized":[]},{"id":"17058","type":"CID","arg1_id":"17024","arg2_id":"17015","normalized":[]},{"id":"17059","type":"CID","arg1_id":"17024","arg2_id":"17019","normalized":[]},{"id":"17060","type":"CID","arg1_id":"17024","arg2_id":"17025","normalized":[]},{"id":"17061","type":"CID","arg1_id":"17024","arg2_id":"17026","normalized":[]},{"id":"17062","type":"CID","arg1_id":"17024","arg2_id":"17027","normalized":[]}]}
{"id":"17063","document_id":"7582165","passages":[{"id":"17064","type":"title","text":["Pseudo-allergic reactions to corticosteroids: diagnosis and alternatives."],"offsets":[[0,73]]},{"id":"17065","type":"abstract","text":["Two patients treated with parenteral paramethasone (Triniol) and dexamethasone (Sedionbel) are described. A few minutes after administration of the drugs, they presented urticaria (patients 1 and 2) and conjunctivitis (patient 1). The purpose of our study was to determine the cause of the patients' reactions, the immunological mechanisms involved and whether these patients would be able to tolerate any kind of corticoid. Clinical examinations and skin, oral and parenteral challenges with different corticosteroids and ELISA tests were performed. In the two patients, skin and ELISA tests with paramethasone were negative, as was the prick test with each of its excipients. A single-blind parenteral challenge with Triniol was positive in both patients after the administration of 1 ml of the drug, and negative with its excipients. We also carried out oral and parenteral challenges with other corticosteroids and found intolerance to some of them. These results suggest that paramethasone caused pseudoallergic reactions in our patients. Corticosteroids different from paramethasone also produced hypersensitivity reactions in these patients; however, a few of them were tolerated. The basic mechanisms of those reactions are not yet fully understood. To our knowledge, this is the first report of a pseudo-allergy caused by paramethasone."],"offsets":[[74,1419]]}],"entities":[{"id":"17066","type":"Disease","text":["allergic reactions"],"offsets":[[7,25]],"normalized":[{"db_name":"MESH","db_id":"D004342"}]},{"id":"17067","type":"Chemical","text":["corticosteroids"],"offsets":[[29,44]],"normalized":[{"db_name":"MESH","db_id":"D000305"}]},{"id":"17068","type":"Chemical","text":["paramethasone"],"offsets":[[111,124]],"normalized":[{"db_name":"MESH","db_id":"D010248"}]},{"id":"17069","type":"Chemical","text":["dexamethasone"],"offsets":[[139,152]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"17070","type":"Disease","text":["urticaria"],"offsets":[[244,253]],"normalized":[{"db_name":"MESH","db_id":"D014581"}]},{"id":"17071","type":"Disease","text":["conjunctivitis"],"offsets":[[277,291]],"normalized":[{"db_name":"MESH","db_id":"D003231"}]},{"id":"17072","type":"Chemical","text":["corticosteroids"],"offsets":[[577,592]],"normalized":[{"db_name":"MESH","db_id":"D000305"}]},{"id":"17073","type":"Chemical","text":["paramethasone"],"offsets":[[672,685]],"normalized":[{"db_name":"MESH","db_id":"D010248"}]},{"id":"17074","type":"Chemical","text":["corticosteroids"],"offsets":[[973,988]],"normalized":[{"db_name":"MESH","db_id":"D000305"}]},{"id":"17075","type":"Chemical","text":["paramethasone"],"offsets":[[1055,1068]],"normalized":[{"db_name":"MESH","db_id":"D010248"}]},{"id":"17076","type":"Chemical","text":["paramethasone"],"offsets":[[1149,1162]],"normalized":[{"db_name":"MESH","db_id":"D010248"}]},{"id":"17077","type":"Disease","text":["hypersensitivity"],"offsets":[[1177,1193]],"normalized":[{"db_name":"MESH","db_id":"D004342"}]},{"id":"17078","type":"Disease","text":["allergy"],"offsets":[[1387,1394]],"normalized":[{"db_name":"MESH","db_id":"D004342"}]},{"id":"17079","type":"Chemical","text":["paramethasone"],"offsets":[[1405,1418]],"normalized":[{"db_name":"MESH","db_id":"D010248"}]}],"events":[],"coreferences":[],"relations":[{"id":"17080","type":"CID","arg1_id":"17068","arg2_id":"17070","normalized":[]},{"id":"17081","type":"CID","arg1_id":"17073","arg2_id":"17070","normalized":[]},{"id":"17082","type":"CID","arg1_id":"17075","arg2_id":"17070","normalized":[]},{"id":"17083","type":"CID","arg1_id":"17076","arg2_id":"17070","normalized":[]},{"id":"17084","type":"CID","arg1_id":"17079","arg2_id":"17070","normalized":[]},{"id":"17085","type":"CID","arg1_id":"17069","arg2_id":"17071","normalized":[]},{"id":"17086","type":"CID","arg1_id":"17069","arg2_id":"17070","normalized":[]},{"id":"17087","type":"CID","arg1_id":"17068","arg2_id":"17071","normalized":[]},{"id":"17088","type":"CID","arg1_id":"17073","arg2_id":"17071","normalized":[]},{"id":"17089","type":"CID","arg1_id":"17075","arg2_id":"17071","normalized":[]},{"id":"17090","type":"CID","arg1_id":"17076","arg2_id":"17071","normalized":[]},{"id":"17091","type":"CID","arg1_id":"17079","arg2_id":"17071","normalized":[]}]}
{"id":"17092","document_id":"16787750","passages":[{"id":"17093","type":"title","text":["Valproic acid induced encephalopathy--19 new cases in Germany from 1994 to 2003--a side effect associated to VPA-therapy not only in young children."],"offsets":[[0,148]]},{"id":"17094","type":"abstract","text":["Valproic acid (VPA) is a broad-spectrum antiepileptic drug and is usually well-tolerated. Rare serious complications may occur in some patients, including haemorrhagic pancreatitis, bone marrow suppression, VPA-induced hepatotoxicity and VPA-induced encephalopathy. The typical signs of VPA-induced encephalopathy are impaired consciousness, sometimes marked EEG background slowing, increased seizure frequency, with or without hyperammonemia. There is still no proof of causative effect of VPA in patients with encephalopathy, but only of an association with an assumed causal relation. We report 19 patients with VPA-associated encephalopathy in Germany from the years 1994 to 2003, none of whom had been published previously."],"offsets":[[149,877]]}],"entities":[{"id":"17095","type":"Chemical","text":["Valproic acid"],"offsets":[[0,13]],"normalized":[{"db_name":"MESH","db_id":"D014635"}]},{"id":"17096","type":"Disease","text":["encephalopathy"],"offsets":[[22,36]],"normalized":[{"db_name":"MESH","db_id":"D001927"}]},{"id":"17097","type":"Chemical","text":["VPA"],"offsets":[[109,112]],"normalized":[{"db_name":"MESH","db_id":"D014635"}]},{"id":"17098","type":"Chemical","text":["Valproic acid"],"offsets":[[149,162]],"normalized":[{"db_name":"MESH","db_id":"D014635"}]},{"id":"17099","type":"Chemical","text":["VPA"],"offsets":[[164,167]],"normalized":[{"db_name":"MESH","db_id":"D014635"}]},{"id":"17100","type":"Disease","text":["pancreatitis"],"offsets":[[317,329]],"normalized":[{"db_name":"MESH","db_id":"D010195"}]},{"id":"17101","type":"Disease","text":["bone marrow 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{"id":"17196","document_id":"3173180","passages":[{"id":"17197","type":"title","text":["Haemolytic-uraemic syndrome after treatment with metronidazole."],"offsets":[[0,63]]},{"id":"17198","type":"abstract","text":["This paper describes the clinical features of six children who developed the haemolytic-uraemic syndrome after treatment with metronidazole. These children were older and were more likely to have undergone recent bowel surgery than are other children with this condition. While the involvement of metronidazole in the aetiology of the haemolytic-uraemic syndrome is not established firmly, the action of this drug in sensitizing tissues to oxidation injury and the reported evidence of oxidation changes in the haemolytic-uraemic syndrome suggest a possible link between metronidazole treatment and some cases of the haemolytic-uraemic syndrome."],"offsets":[[64,709]]}],"entities":[{"id":"17199","type":"Disease","text":["Haemolytic-uraemic syndrome"],"offsets":[[0,27]],"normalized":[{"db_name":"MESH","db_id":"D006463"}]},{"id":"17200","type":"Chemical","text":["metronidazole"],"offsets":[[49,62]],"normalized":[{"db_name":"MESH","db_id":"D008795"}]},{"id":"17201","type":"Disease","text":["haemolytic-uraemic syndrome"],"offsets":[[141,168]],"normalized":[{"db_name":"MESH","db_id":"D006463"}]},{"id":"17202","type":"Chemical","text":["metronidazole"],"offsets":[[190,203]],"normalized":[{"db_name":"MESH","db_id":"D008795"}]},{"id":"17203","type":"Chemical","text":["metronidazole"],"offsets":[[361,374]],"normalized":[{"db_name":"MESH","db_id":"D008795"}]},{"id":"17204","type":"Disease","text":["haemolytic-uraemic syndrome"],"offsets":[[399,426]],"normalized":[{"db_name":"MESH","db_id":"D006463"}]},{"id":"17205","type":"Disease","text":["haemolytic-uraemic syndrome"],"offsets":[[575,602]],"normalized":[{"db_name":"MESH","db_id":"D006463"}]},{"id":"17206","type":"Chemical","text":["metronidazole"],"offsets":[[635,648]],"normalized":[{"db_name":"MESH","db_id":"D008795"}]},{"id":"17207","type":"Disease","text":["haemolytic-uraemic syndrome"],"offsets":[[681,708]],"normalized":[{"db_name":"MESH","db_id":"D006463"}]}],"events":[],"coreferences":[],"relations":[{"id":"17208","type":"CID","arg1_id":"17200","arg2_id":"17199","normalized":[]},{"id":"17209","type":"CID","arg1_id":"17200","arg2_id":"17201","normalized":[]},{"id":"17210","type":"CID","arg1_id":"17200","arg2_id":"17204","normalized":[]},{"id":"17211","type":"CID","arg1_id":"17200","arg2_id":"17205","normalized":[]},{"id":"17212","type":"CID","arg1_id":"17200","arg2_id":"17207","normalized":[]},{"id":"17213","type":"CID","arg1_id":"17202","arg2_id":"17199","normalized":[]},{"id":"17214","type":"CID","arg1_id":"17202","arg2_id":"17201","normalized":[]},{"id":"17215","type":"CID","arg1_id":"17202","arg2_id":"17204","normalized":[]},{"id":"17216","type":"CID","arg1_id":"17202","arg2_id":"17205","normalized":[]},{"id":"17217","type":"CID","arg1_id":"17202","arg2_id":"17207","normalized":[]},{"id":"17218","type":"CID","arg1_id":"17203","arg2_id":"17199","normalized":[]},{"id":"17219","type":"CID","arg1_id":"17203","arg2_id":"17201","normalized":[]},{"id":"17220","type":"CID","arg1_id":"17203","arg2_id":"17204","normalized":[]},{"id":"17221","type":"CID","arg1_id":"17203","arg2_id":"17205","normalized":[]},{"id":"17222","type":"CID","arg1_id":"17203","arg2_id":"17207","normalized":[]},{"id":"17223","type":"CID","arg1_id":"17206","arg2_id":"17199","normalized":[]},{"id":"17224","type":"CID","arg1_id":"17206","arg2_id":"17201","normalized":[]},{"id":"17225","type":"CID","arg1_id":"17206","arg2_id":"17204","normalized":[]},{"id":"17226","type":"CID","arg1_id":"17206","arg2_id":"17205","normalized":[]},{"id":"17227","type":"CID","arg1_id":"17206","arg2_id":"17207","normalized":[]}]}
{"id":"17228","document_id":"8996652","passages":[{"id":"17229","type":"title","text":["Risk factors of sensorineural hearing loss in preterm infants."],"offsets":[[0,62]]},{"id":"17230","type":"abstract","text":["Among 547 preterm infants of < or = 34 weeks gestation born between 1987 and 1991, 8 children (1.46%) developed severe progressive and bilateral sensorineural hearing loss. Perinatal risk factors of infants with hearing loss were compared with those of two control groups matched for gestation and birth weight and for perinatal complications. Our observations demonstrated an association of hearing loss with a higher incidence of perinatal complications. Ototoxicity appeared closely related to a prolonged administration and higher total dose of ototoxic drugs, particularly aminoglycosides and furosemide. Finally, we strongly recommend to prospectively and regularly perform audiologic assessment in sick preterm children as hearing loss is of delayed onset and in most cases bilateral and severe."],"offsets":[[63,865]]}],"entities":[{"id":"17231","type":"Disease","text":["sensorineural hearing loss"],"offsets":[[16,42]],"normalized":[{"db_name":"MESH","db_id":"D006319"}]},{"id":"17232","type":"Disease","text":["sensorineural hearing loss"],"offsets":[[208,234]],"normalized":[{"db_name":"MESH","db_id":"D006319"}]},{"id":"17233","type":"Disease","text":["hearing loss"],"offsets":[[275,287]],"normalized":[{"db_name":"MESH","db_id":"D034381"}]},{"id":"17234","type":"Disease","text":["hearing loss"],"offsets":[[455,467]],"normalized":[{"db_name":"MESH","db_id":"D034381"}]},{"id":"17235","type":"Disease","text":["Ototoxicity"],"offsets":[[520,531]],"normalized":[{"db_name":"MESH","db_id":"D006311"}]},{"id":"17236","type":"Disease","text":["ototoxic"],"offsets":[[612,620]],"normalized":[{"db_name":"MESH","db_id":"D006311"}]},{"id":"17237","type":"Chemical","text":["aminoglycosides"],"offsets":[[641,656]],"normalized":[{"db_name":"MESH","db_id":"D000617"}]},{"id":"17238","type":"Chemical","text":["furosemide"],"offsets":[[661,671]],"normalized":[{"db_name":"MESH","db_id":"D005665"}]},{"id":"17239","type":"Disease","text":["hearing loss"],"offsets":[[793,805]],"normalized":[{"db_name":"MESH","db_id":"D034381"}]}],"events":[],"coreferences":[],"relations":[{"id":"17240","type":"CID","arg1_id":"17237","arg2_id":"17231","normalized":[]},{"id":"17241","type":"CID","arg1_id":"17237","arg2_id":"17232","normalized":[]},{"id":"17242","type":"CID","arg1_id":"17238","arg2_id":"17231","normalized":[]},{"id":"17243","type":"CID","arg1_id":"17238","arg2_id":"17232","normalized":[]}]}
{"id":"17244","document_id":"84204","passages":[{"id":"17245","type":"title","text":["Pharmacokinetic and clinical studies in patients with cimetidine-associated mental confusion."],"offsets":[[0,93]]},{"id":"17246","type":"abstract","text":["15 cases of cimetidine-associated mental confusion have been reported. In order that this syndrome might be investigated changes in mental status (M.S.) were correlated with serum concentrations and renal and hepatic function in 36 patients, 30 patients had no M.S. change on cimetidine and 6 had moderate to severe changes. These 6 patients had both renal and liver dysfunction (P less than 0.05), as well as cimetidine trough-concentrations of more than 1.25 microgram\/ml (P less than 0.05). The severity of M.S. changes increased as trough-concentrations rose, 5 patients had lumbar puncture. The cerebrospinal fluid: serum ratio of cimetidine concentrations was 0.24:1 and indicates that cimetidine passes the blood-brain barrier; it also raises the possibility that M.S. changes are due to blockade of histamine H2-receptors in the central nervous system. Patients likely to have both raised trough-concentrations and mental confusion are those with both severe renal and hepatic dysfunction. They should be closely observed and should be given reduced doses of cimetidine."],"offsets":[[94,1172]]}],"entities":[{"id":"17247","type":"Chemical","text":["cimetidine"],"offsets":[[54,64]],"normalized":[{"db_name":"MESH","db_id":"D002927"}]},{"id":"17248","type":"Disease","text":["confusion"],"offsets":[[83,92]],"normalized":[{"db_name":"MESH","db_id":"D003221"}]},{"id":"17249","type":"Chemical","text":["cimetidine"],"offsets":[[106,116]],"normalized":[{"db_name":"MESH","db_id":"D002927"}]},{"id":"17250","type":"Disease","text":["confusion"],"offsets":[[135,144]],"normalized":[{"db_name":"MESH","db_id":"D003221"}]},{"id":"17251","type":"Chemical","text":["cimetidine"],"offsets":[[370,380]],"normalized":[{"db_name":"MESH","db_id":"D002927"}]},{"id":"17252","type":"Disease","text":["renal and liver dysfunction"],"offsets":[[445,472]],"normalized":[{"db_name":"MESH","db_id":"D051437"},{"db_name":"MESH","db_id":"D008107"}]},{"id":"17253","type":"Disease","text":["renal","dysfunction"],"offsets":[[445,450],[461,472]],"normalized":[{"db_name":"MESH","db_id":"D051437"}]},{"id":"17254","type":"Disease","text":["liver dysfunction"],"offsets":[[455,472]],"normalized":[{"db_name":"MESH","db_id":"D008107"}]},{"id":"17255","type":"Chemical","text":["cimetidine"],"offsets":[[504,514]],"normalized":[{"db_name":"MESH","db_id":"D002927"}]},{"id":"17256","type":"Chemical","text":["cimetidine"],"offsets":[[730,740]],"normalized":[{"db_name":"MESH","db_id":"D002927"}]},{"id":"17257","type":"Chemical","text":["cimetidine"],"offsets":[[786,796]],"normalized":[{"db_name":"MESH","db_id":"D002927"}]},{"id":"17258","type":"Chemical","text":["histamine"],"offsets":[[901,910]],"normalized":[{"db_name":"MESH","db_id":"D006632"}]},{"id":"17259","type":"Disease","text":["confusion"],"offsets":[[1024,1033]],"normalized":[{"db_name":"MESH","db_id":"D003221"}]},{"id":"17260","type":"Disease","text":["renal and hepatic dysfunction"],"offsets":[[1061,1090]],"normalized":[{"db_name":"MESH","db_id":"D051437"},{"db_name":"MESH","db_id":"D008107"}]},{"id":"17261","type":"Disease","text":["renal","dysfunction"],"offsets":[[1061,1066],[1079,1090]],"normalized":[{"db_name":"MESH","db_id":"D051437"}]},{"id":"17262","type":"Disease","text":["hepatic dysfunction"],"offsets":[[1071,1090]],"normalized":[{"db_name":"MESH","db_id":"D008107"}]},{"id":"17263","type":"Chemical","text":["cimetidine"],"offsets":[[1161,1171]],"normalized":[{"db_name":"MESH","db_id":"D002927"}]}],"events":[],"coreferences":[],"relations":[{"id":"17264","type":"CID","arg1_id":"17247","arg2_id":"17248","normalized":[]},{"id":"17265","type":"CID","arg1_id":"17247","arg2_id":"17250","normalized":[]},{"id":"17266","type":"CID","arg1_id":"17247","arg2_id":"17259","normalized":[]},{"id":"17267","type":"CID","arg1_id":"17249","arg2_id":"17248","normalized":[]},{"id":"17268","type":"CID","arg1_id":"17249","arg2_id":"17250","normalized":[]},{"id":"17269","type":"CID","arg1_id":"17249","arg2_id":"17259","normalized":[]},{"id":"17270","type":"CID","arg1_id":"17251","arg2_id":"17248","normalized":[]},{"id":"17271","type":"CID","arg1_id":"17251","arg2_id":"17250","normalized":[]},{"id":"17272","type":"CID","arg1_id":"17251","arg2_id":"17259","normalized":[]},{"id":"17273","type":"CID","arg1_id":"17255","arg2_id":"17248","normalized":[]},{"id":"17274","type":"CID","arg1_id":"17255","arg2_id":"17250","normalized":[]},{"id":"17275","type":"CID","arg1_id":"17255","arg2_id":"17259","normalized":[]},{"id":"17276","type":"CID","arg1_id":"17256","arg2_id":"17248","normalized":[]},{"id":"17277","type":"CID","arg1_id":"17256","arg2_id":"17250","normalized":[]},{"id":"17278","type":"CID","arg1_id":"17256","arg2_id":"17259","normalized":[]},{"id":"17279","type":"CID","arg1_id":"17257","arg2_id":"17248","normalized":[]},{"id":"17280","type":"CID","arg1_id":"17257","arg2_id":"17250","normalized":[]},{"id":"17281","type":"CID","arg1_id":"17257","arg2_id":"17259","normalized":[]},{"id":"17282","type":"CID","arg1_id":"17263","arg2_id":"17248","normalized":[]},{"id":"17283","type":"CID","arg1_id":"17263","arg2_id":"17250","normalized":[]},{"id":"17284","type":"CID","arg1_id":"17263","arg2_id":"17259","normalized":[]}]}
{"id":"17285","document_id":"9862868","passages":[{"id":"17286","type":"title","text":["Different lobular distributions of altered hepatocyte tight junctions in rat models of intrahepatic and extrahepatic cholestasis."],"offsets":[[0,129]]},{"id":"17287","type":"abstract","text":["Hepatocyte tight junctions (TJs), the only intercellular barrier between the sinusoidal and the canalicular spaces, play a key role in bile formation. Although hepatocyte TJs are impaired in cholestasis, attempts to localize the precise site of hepatocyte TJ damage by freeze-fracture electron microscopy have produced limited information. Recently, several TJ-associated proteins like ZO-1 and 7H6 have been identified and characterized. Immunolocalization of 7H6 appears to closely correlate with paracellular permeability. We used rat models of intrahepatic cholestasis by ethinyl estradiol (EE) treatment and extrahepatic cholestasis by bile duct ligation (BDL) to precisely determine the site of TJ damage. Alterations in hepatocyte TJs were assessed by double-immunolabeling for 7H6 and ZO-1 using a confocal laser scanning microscope. In control rats, immunostaining for 7H6 and ZO-1 colocalized to outline bile canaliculi in a continuous fashion. In contrast, 7H6 and ZO-1 immunostaining was more discontinuous, outlining the bile canaliculi after BDL. Immunostaining for 7H6, not ZO-1, decreased and predominantly appeared as discrete signals in the submembranous cytoplasm of periportal hepatocytes after BDL. After EE treatment, changes in immunostaining for 7H6 and ZO-1 were similar to those seen in periportal hepatocytes after BDL, but distributed more diffusely throughout the lobule. This study is the first to demonstrate that impairment of hepatocyte TJs occurs heterogenously in the liver lobule after BDL and suggests that BDL and EE treatments produce different lobular distributions of increased paracellular permeability."],"offsets":[[130,1775]]}],"entities":[{"id":"17288","type":"Disease","text":["intrahepatic and extrahepatic cholestasis"],"offsets":[[87,128]],"normalized":[{"db_name":"MESH","db_id":"D002780"},{"db_name":"MESH","db_id":"D001651"}]},{"id":"17289","type":"Disease","text":["intrahepatic","cholestasis"],"offsets":[[87,99],[117,128]],"normalized":[{"db_name":"MESH","db_id":"D002780"}]},{"id":"17290","type":"Disease","text":["extrahepatic cholestasis"],"offsets":[[104,128]],"normalized":[{"db_name":"MESH","db_id":"D001651"}]},{"id":"17291","type":"Disease","text":["cholestasis"],"offsets":[[321,332]],"normalized":[{"db_name":"MESH","db_id":"D002779"}]},{"id":"17292","type":"Disease","text":["intrahepatic cholestasis"],"offsets":[[678,702]],"normalized":[{"db_name":"MESH","db_id":"D002780"}]},{"id":"17293","type":"Chemical","text":["ethinyl estradiol"],"offsets":[[706,723]],"normalized":[{"db_name":"MESH","db_id":"D004997"}]},{"id":"17294","type":"Chemical","text":["EE"],"offsets":[[725,727]],"normalized":[{"db_name":"MESH","db_id":"D004997"}]},{"id":"17295","type":"Disease","text":["extrahepatic cholestasis"],"offsets":[[743,767]],"normalized":[{"db_name":"MESH","db_id":"D001651"}]},{"id":"17296","type":"Chemical","text":["EE"],"offsets":[[1356,1358]],"normalized":[{"db_name":"MESH","db_id":"D004997"}]},{"id":"17297","type":"Chemical","text":["EE"],"offsets":[[1682,1684]],"normalized":[{"db_name":"MESH","db_id":"D004997"}]}],"events":[],"coreferences":[],"relations":[{"id":"17298","type":"CID","arg1_id":"17293","arg2_id":"17288","normalized":[]},{"id":"17299","type":"CID","arg1_id":"17293","arg2_id":"17289","normalized":[]},{"id":"17300","type":"CID","arg1_id":"17293","arg2_id":"17292","normalized":[]},{"id":"17301","type":"CID","arg1_id":"17294","arg2_id":"17288","normalized":[]},{"id":"17302","type":"CID","arg1_id":"17294","arg2_id":"17289","normalized":[]},{"id":"17303","type":"CID","arg1_id":"17294","arg2_id":"17292","normalized":[]},{"id":"17304","type":"CID","arg1_id":"17296","arg2_id":"17288","normalized":[]},{"id":"17305","type":"CID","arg1_id":"17296","arg2_id":"17289","normalized":[]},{"id":"17306","type":"CID","arg1_id":"17296","arg2_id":"17292","normalized":[]},{"id":"17307","type":"CID","arg1_id":"17297","arg2_id":"17288","normalized":[]},{"id":"17308","type":"CID","arg1_id":"17297","arg2_id":"17289","normalized":[]},{"id":"17309","type":"CID","arg1_id":"17297","arg2_id":"17292","normalized":[]}]}
{"id":"17310","document_id":"15515654","passages":[{"id":"17311","type":"title","text":["Long term audiological evaluation of beta-thalassemic patients."],"offsets":[[0,63]]},{"id":"17312","type":"abstract","text":["OBJECTIVE: The objective of this study was to identify the incidence and to monitor the progression of hearing loss in children and young adults with beta-thalassemia major. METHODS: One hundred and four (104) patients aged 6-35 years (mean 17,2 years) participated in the study. All patients were on a regular transfusion-chelation program maintaining a mean hemoglobin level of 9.5 gr\/dl. Subjects were receiving desferrioxamine (DFO) chelation treatment with a mean daily dose of 50-60 mg\/kg, 5-6 days a week during the first six years of the study, which was then reduced to 40-50 mg\/kg for the following eight years. Patients were followed for 8-14 years. RESULTS: Overall, 21 out of 104 patients (20.2%) presented with high frequency sensorineural hearing loss (SNHL), either unilateral or bilateral. No ototoxic factor, other than DFO, was present in any of the patients. Patients with SNHL presented with relatively lower serum ferritin levels than those with normal hearing, however, no statistically significant difference was observed. Subjects with SNHL were submitted to DFO reduction or temporary withdrawal. Following intervention, 7 out of 21 affected patients recovered, 10 remained stable and 4 demonstrated aggravation. CONCLUSION: The findings are indicative of DFO's contributing role in the development of hearing impairment. Regular audiologic evaluation is imperative in all thalassemic patients so that early changes may be recognized and treatment may be judiciously adjusted in order to prevent or reverse hearing impairment."],"offsets":[[64,1616]]}],"entities":[{"id":"17313","type":"Disease","text":["beta-thalassemic"],"offsets":[[37,53]],"normalized":[{"db_name":"MESH","db_id":"D017086"}]},{"id":"17314","type":"Disease","text":["hearing loss"],"offsets":[[167,179]],"normalized":[{"db_name":"MESH","db_id":"D034381"}]},{"id":"17315","type":"Disease","text":["beta-thalassemia"],"offsets":[[214,230]],"normalized":[{"db_name":"MESH","db_id":"D017086"}]},{"id":"17316","type":"Chemical","text":["desferrioxamine"],"offsets":[[479,494]],"normalized":[{"db_name":"MESH","db_id":"D003676"}]},{"id":"17317","type":"Chemical","text":["DFO"],"offsets":[[496,499]],"normalized":[{"db_name":"MESH","db_id":"D003676"}]},{"id":"17318","type":"Disease","text":["sensorineural hearing loss"],"offsets":[[804,830]],"normalized":[{"db_name":"MESH","db_id":"D006319"}]},{"id":"17319","type":"Disease","text":["SNHL"],"offsets":[[832,836]],"normalized":[{"db_name":"MESH","db_id":"D006319"}]},{"id":"17320","type":"Disease","text":["ototoxic"],"offsets":[[874,882]],"normalized":[{"db_name":"MESH","db_id":"D006311"}]},{"id":"17321","type":"Chemical","text":["DFO"],"offsets":[[902,905]],"normalized":[{"db_name":"MESH","db_id":"D003676"}]},{"id":"17322","type":"Disease","text":["SNHL"],"offsets":[[957,961]],"normalized":[{"db_name":"MESH","db_id":"D006319"}]},{"id":"17323","type":"Disease","text":["SNHL"],"offsets":[[1125,1129]],"normalized":[{"db_name":"MESH","db_id":"D006319"}]},{"id":"17324","type":"Chemical","text":["DFO"],"offsets":[[1148,1151]],"normalized":[{"db_name":"MESH","db_id":"D003676"}]},{"id":"17325","type":"Chemical","text":["DFO"],"offsets":[[1346,1349]],"normalized":[{"db_name":"MESH","db_id":"D003676"}]},{"id":"17326","type":"Disease","text":["hearing impairment"],"offsets":[[1392,1410]],"normalized":[{"db_name":"MESH","db_id":"D034381"}]},{"id":"17327","type":"Disease","text":["thalassemic"],"offsets":[[1463,1474]],"normalized":[{"db_name":"MESH","db_id":"D013789"}]},{"id":"17328","type":"Disease","text":["hearing impairment"],"offsets":[[1597,1615]],"normalized":[{"db_name":"MESH","db_id":"D034381"}]}],"events":[],"coreferences":[],"relations":[{"id":"17329","type":"CID","arg1_id":"17316","arg2_id":"17318","normalized":[]},{"id":"17330","type":"CID","arg1_id":"17316","arg2_id":"17319","normalized":[]},{"id":"17331","type":"CID","arg1_id":"17316","arg2_id":"17322","normalized":[]},{"id":"17332","type":"CID","arg1_id":"17316","arg2_id":"17323","normalized":[]},{"id":"17333","type":"CID","arg1_id":"17317","arg2_id":"17318","normalized":[]},{"id":"17334","type":"CID","arg1_id":"17317","arg2_id":"17319","normalized":[]},{"id":"17335","type":"CID","arg1_id":"17317","arg2_id":"17322","normalized":[]},{"id":"17336","type":"CID","arg1_id":"17317","arg2_id":"17323","normalized":[]},{"id":"17337","type":"CID","arg1_id":"17321","arg2_id":"17318","normalized":[]},{"id":"17338","type":"CID","arg1_id":"17321","arg2_id":"17319","normalized":[]},{"id":"17339","type":"CID","arg1_id":"17321","arg2_id":"17322","normalized":[]},{"id":"17340","type":"CID","arg1_id":"17321","arg2_id":"17323","normalized":[]},{"id":"17341","type":"CID","arg1_id":"17324","arg2_id":"17318","normalized":[]},{"id":"17342","type":"CID","arg1_id":"17324","arg2_id":"17319","normalized":[]},{"id":"17343","type":"CID","arg1_id":"17324","arg2_id":"17322","normalized":[]},{"id":"17344","type":"CID","arg1_id":"17324","arg2_id":"17323","normalized":[]},{"id":"17345","type":"CID","arg1_id":"17325","arg2_id":"17318","normalized":[]},{"id":"17346","type":"CID","arg1_id":"17325","arg2_id":"17319","normalized":[]},{"id":"17347","type":"CID","arg1_id":"17325","arg2_id":"17322","normalized":[]},{"id":"17348","type":"CID","arg1_id":"17325","arg2_id":"17323","normalized":[]}]}
{"id":"17349","document_id":"2024540","passages":[{"id":"17350","type":"title","text":["Design and analysis of the HYPREN-trial: safety of enalapril and prazosin in the initial treatment phase of patients with congestive heart failure."],"offsets":[[0,147]]},{"id":"17351","type":"abstract","text":["Since the introduction of angiotensin converting enzyme (ACE) inhibitors into the adjunctive treatment of patients with congestive heart failure, cases of severe hypotension, especially on the first day of treatment, have occasionally been reported. To assess the safety of the ACE inhibitor enalapril a multicenter, randomized, prazosin-controlled trial was designed that compared the incidence and severity of symptomatic hypotension on the first day of treatment. Trial medication was 2.5 mg enalapril or 0.5 prazosin. Subjects were 1210 inpatients with New York Heart Association (NYHA) functional class II and III. Patients who received enalapril experienced clinically and statistically significantly less symptomatic hypotension (5.2%) than the patients who received prazosin (12.9%). All patients recovered. It was concluded that treatment with enalapril was well tolerated and it is, therefore, unreasonable to restrict the initiation of treatment with enalapril to inpatients."],"offsets":[[148,1134]]}],"entities":[{"id":"17352","type":"Chemical","text":["enalapril"],"offsets":[[51,60]],"normalized":[{"db_name":"MESH","db_id":"D004656"}]},{"id":"17353","type":"Chemical","text":["prazosin"],"offsets":[[65,73]],"normalized":[{"db_name":"MESH","db_id":"D011224"}]},{"id":"17354","type":"Disease","text":["congestive heart failure"],"offsets":[[122,146]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]},{"id":"17355","type":"Chemical","text":["angiotensin converting enzyme (ACE) inhibitors"],"offsets":[[174,220]],"normalized":[{"db_name":"MESH","db_id":"D000806"}]},{"id":"17356","type":"Disease","text":["congestive heart failure"],"offsets":[[268,292]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]},{"id":"17357","type":"Disease","text":["hypotension"],"offsets":[[310,321]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"17358","type":"Chemical","text":["ACE inhibitor"],"offsets":[[426,439]],"normalized":[{"db_name":"MESH","db_id":"D000806"}]},{"id":"17359","type":"Chemical","text":["enalapril"],"offsets":[[440,449]],"normalized":[{"db_name":"MESH","db_id":"D004656"}]},{"id":"17360","type":"Chemical","text":["prazosin"],"offsets":[[477,485]],"normalized":[{"db_name":"MESH","db_id":"D011224"}]},{"id":"17361","type":"Disease","text":["hypotension"],"offsets":[[572,583]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"17362","type":"Chemical","text":["enalapril"],"offsets":[[643,652]],"normalized":[{"db_name":"MESH","db_id":"D004656"}]},{"id":"17363","type":"Chemical","text":["prazosin"],"offsets":[[660,668]],"normalized":[{"db_name":"MESH","db_id":"D011224"}]},{"id":"17364","type":"Chemical","text":["enalapril"],"offsets":[[790,799]],"normalized":[{"db_name":"MESH","db_id":"D004656"}]},{"id":"17365","type":"Disease","text":["hypotension"],"offsets":[[872,883]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"17366","type":"Chemical","text":["prazosin"],"offsets":[[922,930]],"normalized":[{"db_name":"MESH","db_id":"D011224"}]},{"id":"17367","type":"Chemical","text":["enalapril"],"offsets":[[1001,1010]],"normalized":[{"db_name":"MESH","db_id":"D004656"}]},{"id":"17368","type":"Chemical","text":["enalapril"],"offsets":[[1110,1119]],"normalized":[{"db_name":"MESH","db_id":"D004656"}]}],"events":[],"coreferences":[],"relations":[{"id":"17369","type":"CID","arg1_id":"17355","arg2_id":"17357","normalized":[]},{"id":"17370","type":"CID","arg1_id":"17355","arg2_id":"17361","normalized":[]},{"id":"17371","type":"CID","arg1_id":"17355","arg2_id":"17365","normalized":[]},{"id":"17372","type":"CID","arg1_id":"17358","arg2_id":"17357","normalized":[]},{"id":"17373","type":"CID","arg1_id":"17358","arg2_id":"17361","normalized":[]},{"id":"17374","type":"CID","arg1_id":"17358","arg2_id":"17365","normalized":[]},{"id":"17375","type":"CID","arg1_id":"17353","arg2_id":"17357","normalized":[]},{"id":"17376","type":"CID","arg1_id":"17353","arg2_id":"17361","normalized":[]},{"id":"17377","type":"CID","arg1_id":"17353","arg2_id":"17365","normalized":[]},{"id":"17378","type":"CID","arg1_id":"17360","arg2_id":"17357","normalized":[]},{"id":"17379","type":"CID","arg1_id":"17360","arg2_id":"17361","normalized":[]},{"id":"17380","type":"CID","arg1_id":"17360","arg2_id":"17365","normalized":[]},{"id":"17381","type":"CID","arg1_id":"17363","arg2_id":"17357","normalized":[]},{"id":"17382","type":"CID","arg1_id":"17363","arg2_id":"17361","normalized":[]},{"id":"17383","type":"CID","arg1_id":"17363","arg2_id":"17365","normalized":[]},{"id":"17384","type":"CID","arg1_id":"17366","arg2_id":"17357","normalized":[]},{"id":"17385","type":"CID","arg1_id":"17366","arg2_id":"17361","normalized":[]},{"id":"17386","type":"CID","arg1_id":"17366","arg2_id":"17365","normalized":[]}]}
{"id":"17387","document_id":"12090760","passages":[{"id":"17388","type":"title","text":["Antagonism between interleukin 3 and erythropoietin in mice with azidothymidine-induced anemia and in bone marrow endothelial cells."],"offsets":[[0,132]]},{"id":"17389","type":"abstract","text":["Azidothymidine (AZT)-induced anemia in mice can be reversed by the administration of IGF-IL-3 (fusion protein of insulin-like growth factor II (IGF II) and interleukin 3). Although interleukin 3 (IL-3) and erythropoietin (EPO) are known to act synergistically on hematopoietic cell proliferation in vitro, injection of IGF-IL-3 and EPO in AZT-treated mice resulted in a reduction of red cells and an increase of plasma EPO levels as compared to animals treated with IGF-IL-3 or EPO alone. We tested the hypothesis that the antagonistic effect of IL-3 and EPO on erythroid cells may be mediated by endothelial cells. Bovine liver erythroid cells were cultured on monolayers of human bone marrow endothelial cells previously treated with EPO and IGF-IL-3. There was a significant reduction of thymidine incorporation into both erythroid and endothelial cells in cultures pre-treated with IGF-IL-3 and EPO. Endothelial cell culture supernatants separated by ultrafiltration and ultracentrifugation from cells treated with EPO and IL-3 significantly reduced thymidine incorporation into erythroid cells as compared to identical fractions obtained from the media of cells cultured with EPO alone. These results suggest that endothelial cells treated simultaneously with EPO and IL-3 have a negative effect on erythroid cell production."],"offsets":[[133,1463]]}],"entities":[{"id":"17390","type":"Chemical","text":["azidothymidine"],"offsets":[[65,79]],"normalized":[{"db_name":"MESH","db_id":"D015215"}]},{"id":"17391","type":"Disease","text":["anemia"],"offsets":[[88,94]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]},{"id":"17392","type":"Chemical","text":["Azidothymidine"],"offsets":[[133,147]],"normalized":[{"db_name":"MESH","db_id":"D015215"}]},{"id":"17393","type":"Chemical","text":["AZT"],"offsets":[[149,152]],"normalized":[{"db_name":"MESH","db_id":"D015215"}]},{"id":"17394","type":"Disease","text":["anemia"],"offsets":[[162,168]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]},{"id":"17395","type":"Chemical","text":["AZT"],"offsets":[[472,475]],"normalized":[{"db_name":"MESH","db_id":"D015215"}]},{"id":"17396","type":"Chemical","text":["thymidine"],"offsets":[[924,933]],"normalized":[{"db_name":"MESH","db_id":"D013936"}]},{"id":"17397","type":"Chemical","text":["thymidine"],"offsets":[[1187,1196]],"normalized":[{"db_name":"MESH","db_id":"D013936"}]}],"events":[],"coreferences":[],"relations":[{"id":"17398","type":"CID","arg1_id":"17390","arg2_id":"17391","normalized":[]},{"id":"17399","type":"CID","arg1_id":"17390","arg2_id":"17394","normalized":[]},{"id":"17400","type":"CID","arg1_id":"17392","arg2_id":"17391","normalized":[]},{"id":"17401","type":"CID","arg1_id":"17392","arg2_id":"17394","normalized":[]},{"id":"17402","type":"CID","arg1_id":"17393","arg2_id":"17391","normalized":[]},{"id":"17403","type":"CID","arg1_id":"17393","arg2_id":"17394","normalized":[]},{"id":"17404","type":"CID","arg1_id":"17395","arg2_id":"17391","normalized":[]},{"id":"17405","type":"CID","arg1_id":"17395","arg2_id":"17394","normalized":[]}]}
{"id":"17406","document_id":"7516729","passages":[{"id":"17407","type":"title","text":["Interactive effects of variations in [Na]o and [Ca]o on rat atrial spontaneous frequency."],"offsets":[[0,89]]},{"id":"17408","type":"abstract","text":["The effects of varying the extracellular concentrations of Na and Ca ([Na]o and [Ca]o) on both, the spontaneous beating and the negative chronotropic action of verapamil, were studied in the isolated rat atria. Basal frequency (BF) evaluated by surface electrogram was 223 +\/- 4 beats\/min. in control Krebs-Ringer containing 137 mM Na and 1.35 mM Ca (N). It decreased by 16 +\/- 3% by lowering [Na]o to 78 mM (LNa), 23 +\/- 2% by lowering simultaneously [Na]o to 78 mM and [Ca]o to 0.675 mM (LNa+LCa) and 31 +\/- 5% by lowering [Na]o to 78 mM plus increasing [Ca]o to 3.6 mM (LNa+HCa). At normal [Na]o, decrease (0.675 mM) or increase (3.6 mM) of [Ca]o did not modify BF; a reduction of ten times (0.135 mM of normal [Ca]o was effective to reduce BF by 40 +\/- 13%. All negative chronotropic effects were BF-dependent. Dose-dependent bradycardia induced by verapamil was potentiated by LNa, LCa, and HCa. Independent but not additive effects of Na and Ca are shown by decreases in the values of [verapamil]o needed to reduce BF by 30% (IC30) with the following order of inhibitory potency: LNa > LCa > HCa > N, resulting LNa+HCa similar to LNa. The [verapamil]o that arrested atrial beating (AC) was also potentiated with the order LNa = LNa+LCa = LNa+HCa = LCa > HCa = N. The results indicate that rat atrial spontaneous beating is more dependent on [Na]o than on [Ca]o in a range of +\/- 50% of their normal concentration. Also the enhancement of verapamil effects on atrial beating was more pronounced at LNa than at LCa.(ABSTRACT TRUNCATED AT 250 WORDS)"],"offsets":[[90,1642]]}],"entities":[{"id":"17409","type":"Chemical","text":["Na"],"offsets":[[38,40]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"17410","type":"Chemical","text":["Ca"],"offsets":[[48,50]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"17411","type":"Chemical","text":["Na"],"offsets":[[149,151]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"17412","type":"Chemical","text":["Ca"],"offsets":[[156,158]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"17413","type":"Chemical","text":["Na"],"offsets":[[161,163]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"17414","type":"Chemical","text":["Ca"],"offsets":[[171,173]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"17415","type":"Chemical","text":["verapamil"],"offsets":[[250,259]],"normalized":[{"db_name":"MESH","db_id":"D014700"}]},{"id":"17416","type":"Chemical","text":["Na"],"offsets":[[422,424]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"17417","type":"Chemical","text":["Ca"],"offsets":[[437,439]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"17418","type":"Chemical","text":["Na"],"offsets":[[484,486]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"17419","type":"Chemical","text":["Na"],"offsets":[[543,545]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"17420","type":"Chemical","text":["Ca"],"offsets":[[562,564]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"17421","type":"Chemical","text":["Na"],"offsets":[[616,618]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"17422","type":"Chemical","text":["Ca"],"offsets":[[647,649]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"17423","type":"Chemical","text":["Na"],"offsets":[[684,686]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"17424","type":"Chemical","text":["Ca"],"offsets":[[735,737]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"17425","type":"Chemical","text":["Ca"],"offsets":[[805,807]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"17426","type":"Disease","text":["bradycardia"],"offsets":[[920,931]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"17427","type":"Chemical","text":["verapamil"],"offsets":[[943,952]],"normalized":[{"db_name":"MESH","db_id":"D014700"}]},{"id":"17428","type":"Chemical","text":["Na"],"offsets":[[1031,1033]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"17429","type":"Chemical","text":["Ca"],"offsets":[[1038,1040]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"17430","type":"Chemical","text":["verapamil"],"offsets":[[1082,1091]],"normalized":[{"db_name":"MESH","db_id":"D014700"}]},{"id":"17431","type":"Chemical","text":["verapamil"],"offsets":[[1236,1245]],"normalized":[{"db_name":"MESH","db_id":"D014700"}]},{"id":"17432","type":"Chemical","text":["Na"],"offsets":[[1438,1440]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"17433","type":"Chemical","text":["Ca"],"offsets":[[1452,1454]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"17434","type":"Chemical","text":["verapamil"],"offsets":[[1534,1543]],"normalized":[{"db_name":"MESH","db_id":"D014700"}]}],"events":[],"coreferences":[],"relations":[{"id":"17435","type":"CID","arg1_id":"17415","arg2_id":"17426","normalized":[]},{"id":"17436","type":"CID","arg1_id":"17427","arg2_id":"17426","normalized":[]},{"id":"17437","type":"CID","arg1_id":"17430","arg2_id":"17426","normalized":[]},{"id":"17438","type":"CID","arg1_id":"17431","arg2_id":"17426","normalized":[]},{"id":"17439","type":"CID","arg1_id":"17434","arg2_id":"17426","normalized":[]}]}
{"id":"17440","document_id":"2802551","passages":[{"id":"17441","type":"title","text":["Sodium status influences chronic amphotericin B nephrotoxicity in rats."],"offsets":[[0,71]]},{"id":"17442","type":"abstract","text":["The nephrotoxic potential of amphotericin B (5 mg\/kg per day intraperitoneally for 3 weeks) has been investigated in salt-depleted, normal-salt, and salt-loaded rats. In salt-depleted rats, amphotericin B decreased creatinine clearance linearly with time, with an 85% reduction by week 3. In contrast, in normal-salt rats creatinine clearance was decreased but to a lesser extent at week 2 and 3, and in salt-loaded rats creatinine clearance did not change for 2 weeks and was decreased by 43% at week 3. All rats in the sodium-depleted group had histopathological evidence of patchy tubular cytoplasmic degeneration in tubules that was not observed in any normal-salt or salt-loaded rat. Concentrations of amphotericin B in plasma were not significantly different among the three groups at any time during the study. However, at the end of 3 weeks, amphotericin B levels in the kidneys and liver were significantly higher in salt-depleted and normal-salt rats than those in salt-loaded rats, with plasma\/kidney ratios of 21, 14, and 8 in salt-depleted, normal-salt, and salt-loaded rats, respectively. In conclusion, reductions in creatinine clearance and renal amphotericin B accumulation after chronic amphotericin B administration were enhanced by salt depletion and attenuated by sodium loading in rats."],"offsets":[[72,1380]]}],"entities":[{"id":"17443","type":"Chemical","text":["Sodium"],"offsets":[[0,6]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"17444","type":"Chemical","text":["amphotericin B"],"offsets":[[33,47]],"normalized":[{"db_name":"MESH","db_id":"D000666"}]},{"id":"17445","type":"Disease","text":["nephrotoxicity"],"offsets":[[48,62]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"17446","type":"Disease","text":["nephrotoxic"],"offsets":[[76,87]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"17447","type":"Chemical","text":["amphotericin B"],"offsets":[[101,115]],"normalized":[{"db_name":"MESH","db_id":"D000666"}]},{"id":"17448","type":"Chemical","text":["amphotericin B"],"offsets":[[262,276]],"normalized":[{"db_name":"MESH","db_id":"D000666"}]},{"id":"17449","type":"Chemical","text":["creatinine"],"offsets":[[287,297]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"17450","type":"Chemical","text":["creatinine"],"offsets":[[394,404]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"17451","type":"Chemical","text":["creatinine"],"offsets":[[493,503]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"17452","type":"Chemical","text":["sodium"],"offsets":[[593,599]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"17453","type":"Chemical","text":["amphotericin B"],"offsets":[[779,793]],"normalized":[{"db_name":"MESH","db_id":"D000666"}]},{"id":"17454","type":"Chemical","text":["amphotericin B"],"offsets":[[922,936]],"normalized":[{"db_name":"MESH","db_id":"D000666"}]},{"id":"17455","type":"Chemical","text":["creatinine"],"offsets":[[1204,1214]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"17456","type":"Chemical","text":["amphotericin B"],"offsets":[[1235,1249]],"normalized":[{"db_name":"MESH","db_id":"D000666"}]},{"id":"17457","type":"Chemical","text":["amphotericin B"],"offsets":[[1277,1291]],"normalized":[{"db_name":"MESH","db_id":"D000666"}]},{"id":"17458","type":"Chemical","text":["sodium"],"offsets":[[1357,1363]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]}],"events":[],"coreferences":[],"relations":[{"id":"17459","type":"CID","arg1_id":"17444","arg2_id":"17445","normalized":[]},{"id":"17460","type":"CID","arg1_id":"17444","arg2_id":"17446","normalized":[]},{"id":"17461","type":"CID","arg1_id":"17447","arg2_id":"17445","normalized":[]},{"id":"17462","type":"CID","arg1_id":"17447","arg2_id":"17446","normalized":[]},{"id":"17463","type":"CID","arg1_id":"17448","arg2_id":"17445","normalized":[]},{"id":"17464","type":"CID","arg1_id":"17448","arg2_id":"17446","normalized":[]},{"id":"17465","type":"CID","arg1_id":"17453","arg2_id":"17445","normalized":[]},{"id":"17466","type":"CID","arg1_id":"17453","arg2_id":"17446","normalized":[]},{"id":"17467","type":"CID","arg1_id":"17454","arg2_id":"17445","normalized":[]},{"id":"17468","type":"CID","arg1_id":"17454","arg2_id":"17446","normalized":[]},{"id":"17469","type":"CID","arg1_id":"17456","arg2_id":"17445","normalized":[]},{"id":"17470","type":"CID","arg1_id":"17456","arg2_id":"17446","normalized":[]},{"id":"17471","type":"CID","arg1_id":"17457","arg2_id":"17445","normalized":[]},{"id":"17472","type":"CID","arg1_id":"17457","arg2_id":"17446","normalized":[]}]}
{"id":"17473","document_id":"19346865","passages":[{"id":"17474","type":"title","text":["Reversible inferior colliculus lesion in metronidazole-induced encephalopathy: magnetic resonance findings on diffusion-weighted and fluid attenuated inversion recovery imaging."],"offsets":[[0,177]]},{"id":"17475","type":"abstract","text":["OBJECTIVE: This is to present reversible inferior colliculus lesions in metronidazole-induced encephalopathy, to focus on the diffusion-weighted imaging (DWI) and fluid attenuated inversion recovery (FLAIR) imaging. MATERIALS AND METHODS: From November 2005 to September 2007, 8 patients (5 men and 3 women) were diagnosed as having metronidazole-induced encephalopathy (age range; 43-78 years). They had been taking metronidazole (total dosage, 45-120 g; duration, 30 days to 2 months) to treat the infection in various organs. Initial brain magnetic resonance imaging (MRI) were obtained after the hospitalization, including DWI (8\/8), apparent diffusion coefficient (ADC) map (4\/8), FLAIR (7\/8), and T2-weighted image (8\/8). Follow-up MRIs were performed on 5 patients from third to 14th days after discontinuation of metronidazole administration. Findings of initial and follow-up MRIs were retrospectively evaluated by 2 neuroradiologists by consensus, to analyze the presence of abnormal signal intensities, their locations, and signal changes on follow-up images. RESULTS: Initial MRIs showed abnormal high signal intensities on DWI and FLAIR (or T2-weighted image) at the dentate nucleus (8\/8), inferior colliculus (6\/8), corpus callosum (2\/8), pons (2\/8), medulla (1\/8), and bilateral cerebral white matter (1\/8). High-signal intensity lesions on DWI tended to show low signal intensity on ADC map (3\/4), but in one patient, high signal intensity was shown at bilateral dentate nuclei on not only DWI but also ADC map. All the lesions in dentate, inferior colliculus, pons, and medullas had been resolved completely on follow-up MRIs in 5 patients, but in 1 patient of them, corpus callosal lesion persisted. CONCLUSIONS: Reversible inferior colliculus lesions could be considered as the characteristic for metronidazole-induced encephalopathy, next to the dentate nucleus involvement."],"offsets":[[178,2072]]}],"entities":[{"id":"17476","type":"Disease","text":["inferior colliculus lesion"],"offsets":[[11,37]],"normalized":[{"db_name":"MESH","db_id":"D001927"}]},{"id":"17477","type":"Chemical","text":["metronidazole"],"offsets":[[41,54]],"normalized":[{"db_name":"MESH","db_id":"D008795"}]},{"id":"17478","type":"Disease","text":["encephalopathy"],"offsets":[[63,77]],"normalized":[{"db_name":"MESH","db_id":"D001927"}]},{"id":"17479","type":"Disease","text":["inferior colliculus lesions"],"offsets":[[219,246]],"normalized":[{"db_name":"MESH","db_id":"D001927"}]},{"id":"17480","type":"Chemical","text":["metronidazole"],"offsets":[[250,263]],"normalized":[{"db_name":"MESH","db_id":"D008795"}]},{"id":"17481","type":"Disease","text":["encephalopathy"],"offsets":[[272,286]],"normalized":[{"db_name":"MESH","db_id":"D001927"}]},{"id":"17482","type":"Chemical","text":["metronidazole"],"offsets":[[511,524]],"normalized":[{"db_name":"MESH","db_id":"D008795"}]},{"id":"17483","type":"Disease","text":["encephalopathy"],"offsets":[[533,547]],"normalized":[{"db_name":"MESH","db_id":"D001927"}]},{"id":"17484","type":"Chemical","text":["metronidazole"],"offsets":[[595,608]],"normalized":[{"db_name":"MESH","db_id":"D008795"}]},{"id":"17485","type":"Disease","text":["infection"],"offsets":[[678,687]],"normalized":[{"db_name":"MESH","db_id":"D007239"}]},{"id":"17486","type":"Chemical","text":["metronidazole"],"offsets":[[999,1012]],"normalized":[{"db_name":"MESH","db_id":"D008795"}]},{"id":"17487","type":"Disease","text":["callosal lesion"],"offsets":[[1869,1884]],"normalized":[{"db_name":"MESH","db_id":"D001927"}]},{"id":"17488","type":"Disease","text":["inferior colliculus lesions"],"offsets":[[1920,1947]],"normalized":[{"db_name":"MESH","db_id":"D001927"}]},{"id":"17489","type":"Chemical","text":["metronidazole"],"offsets":[[1994,2007]],"normalized":[{"db_name":"MESH","db_id":"D008795"}]},{"id":"17490","type":"Disease","text":["encephalopathy"],"offsets":[[2016,2030]],"normalized":[{"db_name":"MESH","db_id":"D001927"}]}],"events":[],"coreferences":[],"relations":[{"id":"17491","type":"CID","arg1_id":"17477","arg2_id":"17476","normalized":[]},{"id":"17492","type":"CID","arg1_id":"17477","arg2_id":"17478","normalized":[]},{"id":"17493","type":"CID","arg1_id":"17477","arg2_id":"17479","normalized":[]},{"id":"17494","type":"CID","arg1_id":"17477","arg2_id":"17481","normalized":[]},{"id":"17495","type":"CID","arg1_id":"17477","arg2_id":"17483","normalized":[]},{"id":"17496","type":"CID","arg1_id":"17477","arg2_id":"17487","normalized":[]},{"id":"17497","type":"CID","arg1_id":"17477","arg2_id":"17488","normalized":[]},{"id":"17498","type":"CID","arg1_id":"17477","arg2_id":"17490","normalized":[]},{"id":"17499","type":"CID","arg1_id":"17480","arg2_id":"17476","normalized":[]},{"id":"17500","type":"CID","arg1_id":"17480","arg2_id":"17478","normalized":[]},{"id":"17501","type":"CID","arg1_id":"17480","arg2_id":"17479","normalized":[]},{"id":"17502","type":"CID","arg1_id":"17480","arg2_id":"17481","normalized":[]},{"id":"17503","type":"CID","arg1_id":"17480","arg2_id":"17483","normalized":[]},{"id":"17504","type":"CID","arg1_id":"17480","arg2_id":"17487","normalized":[]},{"id":"17505","type":"CID","arg1_id":"17480","arg2_id":"17488","normalized":[]},{"id":"17506","type":"CID","arg1_id":"17480","arg2_id":"17490","normalized":[]},{"id":"17507","type":"CID","arg1_id":"17482","arg2_id":"17476","normalized":[]},{"id":"17508","type":"CID","arg1_id":"17482","arg2_id":"17478","normalized":[]},{"id":"17509","type":"CID","arg1_id":"17482","arg2_id":"17479","normalized":[]},{"id":"17510","type":"CID","arg1_id":"17482","arg2_id":"17481","normalized":[]},{"id":"17511","type":"CID","arg1_id":"17482","arg2_id":"17483","normalized":[]},{"id":"17512","type":"CID","arg1_id":"17482","arg2_id":"17487","normalized":[]},{"id":"17513","type":"CID","arg1_id":"17482","arg2_id":"17488","normalized":[]},{"id":"17514","type":"CID","arg1_id":"17482","arg2_id":"17490","normalized":[]},{"id":"17515","type":"CID","arg1_id":"17484","arg2_id":"17476","normalized":[]},{"id":"17516","type":"CID","arg1_id":"17484","arg2_id":"17478","normalized":[]},{"id":"17517","type":"CID","arg1_id":"17484","arg2_id":"17479","normalized":[]},{"id":"17518","type":"CID","arg1_id":"17484","arg2_id":"17481","normalized":[]},{"id":"17519","type":"CID","arg1_id":"17484","arg2_id":"17483","normalized":[]},{"id":"17520","type":"CID","arg1_id":"17484","arg2_id":"17487","normalized":[]},{"id":"17521","type":"CID","arg1_id":"17484","arg2_id":"17488","normalized":[]},{"id":"17522","type":"CID","arg1_id":"17484","arg2_id":"17490","normalized":[]},{"id":"17523","type":"CID","arg1_id":"17486","arg2_id":"17476","normalized":[]},{"id":"17524","type":"CID","arg1_id":"17486","arg2_id":"17478","normalized":[]},{"id":"17525","type":"CID","arg1_id":"17486","arg2_id":"17479","normalized":[]},{"id":"17526","type":"CID","arg1_id":"17486","arg2_id":"17481","normalized":[]},{"id":"17527","type":"CID","arg1_id":"17486","arg2_id":"17483","normalized":[]},{"id":"17528","type":"CID","arg1_id":"17486","arg2_id":"17487","normalized":[]},{"id":"17529","type":"CID","arg1_id":"17486","arg2_id":"17488","normalized":[]},{"id":"17530","type":"CID","arg1_id":"17486","arg2_id":"17490","normalized":[]},{"id":"17531","type":"CID","arg1_id":"17489","arg2_id":"17476","normalized":[]},{"id":"17532","type":"CID","arg1_id":"17489","arg2_id":"17478","normalized":[]},{"id":"17533","type":"CID","arg1_id":"17489","arg2_id":"17479","normalized":[]},{"id":"17534","type":"CID","arg1_id":"17489","arg2_id":"17481","normalized":[]},{"id":"17535","type":"CID","arg1_id":"17489","arg2_id":"17483","normalized":[]},{"id":"17536","type":"CID","arg1_id":"17489","arg2_id":"17487","normalized":[]},{"id":"17537","type":"CID","arg1_id":"17489","arg2_id":"17488","normalized":[]},{"id":"17538","type":"CID","arg1_id":"17489","arg2_id":"17490","normalized":[]}]}
{"id":"17539","document_id":"2334618","passages":[{"id":"17540","type":"title","text":["Comparison of the respiratory effects of i.v. infusions of morphine and regional analgesia by extradural block."],"offsets":[[0,111]]},{"id":"17541","type":"abstract","text":["The incidence of postoperative respiratory apnoea was compared between five patients receiving a continuous i.v. infusion of morphine (mean 73.6 mg) and five patients receiving a continuous extradural infusion of 0.25% bupivacaine (mean 192 mg) in the 24-h period following upper abdominal surgery. Monitoring consisted of airflow detection by a carbon dioxide analyser, chest wall movement detected by pneumatic capsules, and continuous electrocardiograph recorded with a Holter ambulatory monitor. Both obstructive (P less than 0.05) and central apnoea (P less than 0.05) occurred more frequently in patients who had a morphine infusion. There was also a higher incidence of tachyarrhythmias (P less than 0.05) and ventricular ectopic beats (P less than 0.05) in the morphine infusion group."],"offsets":[[112,905]]}],"entities":[{"id":"17542","type":"Chemical","text":["morphine"],"offsets":[[59,67]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"17543","type":"Disease","text":["apnoea"],"offsets":[[155,161]],"normalized":[{"db_name":"MESH","db_id":"D001049"}]},{"id":"17544","type":"Chemical","text":["morphine"],"offsets":[[237,245]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"17545","type":"Chemical","text":["bupivacaine"],"offsets":[[331,342]],"normalized":[{"db_name":"MESH","db_id":"D002045"}]},{"id":"17546","type":"Chemical","text":["carbon dioxide"],"offsets":[[458,472]],"normalized":[{"db_name":"MESH","db_id":"D002245"}]},{"id":"17547","type":"Disease","text":["obstructive (P less than 0.05) and central apnoea"],"offsets":[[617,666]],"normalized":[{"db_name":"MESH","db_id":"D020181"},{"db_name":"MESH","db_id":"D020182"}]},{"id":"17548","type":"Disease","text":["obstructive (P less than 0.05)","apnoea"],"offsets":[[617,647],[660,666]],"normalized":[{"db_name":"MESH","db_id":"D020181"}]},{"id":"17549","type":"Disease","text":["central apnoea"],"offsets":[[652,666]],"normalized":[{"db_name":"MESH","db_id":"D020182"}]},{"id":"17550","type":"Chemical","text":["morphine"],"offsets":[[733,741]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"17551","type":"Disease","text":["tachyarrhythmias"],"offsets":[[789,805]],"normalized":[{"db_name":"MESH","db_id":"D013610"}]},{"id":"17552","type":"Disease","text":["ventricular ectopic beats"],"offsets":[[829,854]],"normalized":[{"db_name":"MESH","db_id":"D018879"}]},{"id":"17553","type":"Chemical","text":["morphine"],"offsets":[[881,889]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]}],"events":[],"coreferences":[],"relations":[{"id":"17554","type":"CID","arg1_id":"17542","arg2_id":"17547","normalized":[]},{"id":"17555","type":"CID","arg1_id":"17542","arg2_id":"17549","normalized":[]},{"id":"17556","type":"CID","arg1_id":"17544","arg2_id":"17547","normalized":[]},{"id":"17557","type":"CID","arg1_id":"17544","arg2_id":"17549","normalized":[]},{"id":"17558","type":"CID","arg1_id":"17550","arg2_id":"17547","normalized":[]},{"id":"17559","type":"CID","arg1_id":"17550","arg2_id":"17549","normalized":[]},{"id":"17560","type":"CID","arg1_id":"17553","arg2_id":"17547","normalized":[]},{"id":"17561","type":"CID","arg1_id":"17553","arg2_id":"17549","normalized":[]},{"id":"17562","type":"CID","arg1_id":"17542","arg2_id":"17547","normalized":[]},{"id":"17563","type":"CID","arg1_id":"17542","arg2_id":"17548","normalized":[]},{"id":"17564","type":"CID","arg1_id":"17544","arg2_id":"17547","normalized":[]},{"id":"17565","type":"CID","arg1_id":"17544","arg2_id":"17548","normalized":[]},{"id":"17566","type":"CID","arg1_id":"17550","arg2_id":"17547","normalized":[]},{"id":"17567","type":"CID","arg1_id":"17550","arg2_id":"17548","normalized":[]},{"id":"17568","type":"CID","arg1_id":"17553","arg2_id":"17547","normalized":[]},{"id":"17569","type":"CID","arg1_id":"17553","arg2_id":"17548","normalized":[]},{"id":"17570","type":"CID","arg1_id":"17542","arg2_id":"17552","normalized":[]},{"id":"17571","type":"CID","arg1_id":"17544","arg2_id":"17552","normalized":[]},{"id":"17572","type":"CID","arg1_id":"17550","arg2_id":"17552","normalized":[]},{"id":"17573","type":"CID","arg1_id":"17553","arg2_id":"17552","normalized":[]}]}
{"id":"17574","document_id":"8864707","passages":[{"id":"17575","type":"title","text":["Magnetic resonance volumetry of the cerebellum in epileptic patients after phenytoin overdosages."],"offsets":[[0,97]]},{"id":"17576","type":"abstract","text":["The aim of this study was to evaluate the relationship between phenytoin medication and cerebellar atrophy in patients who had experienced clinical intoxication. Five females and 6 males, 21-59 years of age, were examined with a 1.5-T whole-body system using a circular polarized head coil. Conventional spin echo images were acquired in the sagittal and transverse orientation. In addition, we performed a high-resolution 3D gradient echo, T1-weighted sequences at a 1-mm slice thickness. The images were subsequently processed to obtain volumetric data for the cerebellum. Cerebellar volume for the patient group ranged between 67.66 and 131.08 ml (mean 108.9 ml). In addition 3D gradient echo data sets from 10 healthy male and 10 healthy female age-matched volunteers were used to compare cerebellar volumes. Using linear regression we found that no correlation exists between seizure duration, elevation of phenytoin serum levels and cerebellar volume. However, multiple regression for the daily dosage, duration of phenytoin treatment and cerebellar volume revealed a correlation of these parameters. We conclude that phenytoin overdosage does not necessarily result in cerebellar atrophy and it is unlikely that phenytoin medication was the only cause of cerebellar atrophy in the remaining patients. Quantitative morphometric studies of the cerebellum provide valuable insights into the pathogenesis of cerebellar disorders."],"offsets":[[98,1530]]}],"entities":[{"id":"17577","type":"Disease","text":["epileptic"],"offsets":[[50,59]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"17578","type":"Chemical","text":["phenytoin"],"offsets":[[75,84]],"normalized":[{"db_name":"MESH","db_id":"D010672"}]},{"id":"17579","type":"Disease","text":["overdosages"],"offsets":[[85,96]],"normalized":[{"db_name":"MESH","db_id":"D062787"}]},{"id":"17580","type":"Chemical","text":["phenytoin"],"offsets":[[161,170]],"normalized":[{"db_name":"MESH","db_id":"D010672"}]},{"id":"17581","type":"Disease","text":["cerebellar atrophy"],"offsets":[[186,204]],"normalized":[{"db_name":"MESH","db_id":"D002526"}]},{"id":"17582","type":"Disease","text":["seizure"],"offsets":[[979,986]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"17583","type":"Chemical","text":["phenytoin"],"offsets":[[1010,1019]],"normalized":[{"db_name":"MESH","db_id":"D010672"}]},{"id":"17584","type":"Chemical","text":["phenytoin"],"offsets":[[1119,1128]],"normalized":[{"db_name":"MESH","db_id":"D010672"}]},{"id":"17585","type":"Chemical","text":["phenytoin"],"offsets":[[1222,1231]],"normalized":[{"db_name":"MESH","db_id":"D010672"}]},{"id":"17586","type":"Disease","text":["overdosage"],"offsets":[[1232,1242]],"normalized":[{"db_name":"MESH","db_id":"D062787"}]},{"id":"17587","type":"Disease","text":["cerebellar atrophy"],"offsets":[[1274,1292]],"normalized":[{"db_name":"MESH","db_id":"D002526"}]},{"id":"17588","type":"Chemical","text":["phenytoin"],"offsets":[[1317,1326]],"normalized":[{"db_name":"MESH","db_id":"D010672"}]},{"id":"17589","type":"Disease","text":["cerebellar atrophy"],"offsets":[[1360,1378]],"normalized":[{"db_name":"MESH","db_id":"D002526"}]},{"id":"17590","type":"Disease","text":["cerebellar disorders"],"offsets":[[1509,1529]],"normalized":[{"db_name":"MESH","db_id":"D002526"}]}],"events":[],"coreferences":[],"relations":[{"id":"17591","type":"CID","arg1_id":"17578","arg2_id":"17579","normalized":[]},{"id":"17592","type":"CID","arg1_id":"17578","arg2_id":"17586","normalized":[]},{"id":"17593","type":"CID","arg1_id":"17580","arg2_id":"17579","normalized":[]},{"id":"17594","type":"CID","arg1_id":"17580","arg2_id":"17586","normalized":[]},{"id":"17595","type":"CID","arg1_id":"17583","arg2_id":"17579","normalized":[]},{"id":"17596","type":"CID","arg1_id":"17583","arg2_id":"17586","normalized":[]},{"id":"17597","type":"CID","arg1_id":"17584","arg2_id":"17579","normalized":[]},{"id":"17598","type":"CID","arg1_id":"17584","arg2_id":"17586","normalized":[]},{"id":"17599","type":"CID","arg1_id":"17585","arg2_id":"17579","normalized":[]},{"id":"17600","type":"CID","arg1_id":"17585","arg2_id":"17586","normalized":[]},{"id":"17601","type":"CID","arg1_id":"17588","arg2_id":"17579","normalized":[]},{"id":"17602","type":"CID","arg1_id":"17588","arg2_id":"17586","normalized":[]}]}
{"id":"17603","document_id":"12589964","passages":[{"id":"17604","type":"title","text":["Evaluation of cardiac troponin I and T levels as markers of myocardial damage in doxorubicin-induced cardiomyopathy rats, and their relationship with echocardiographic and histological findings."],"offsets":[[0,194]]},{"id":"17605","type":"abstract","text":["BACKGROUND: Cardiac troponins I (cTnI) and T (cTnT) have been shown to be highly sensitive and specific markers of myocardial cell injury. We investigated the diagnostic value of cTnI and cTnT for the diagnosis of myocardial damage in a rat model of doxorubicin (DOX)-induced cardiomyopathy, and we examined the relationship between serial cTnI and cTnT with the development of cardiac disorders monitored by echocardiography and histological examinations in this model. METHODS: Thirty-five Wistar rats were given 1.5 mg\/kg DOX, i.v., weekly for up to 8 weeks for a total cumulative dose of 12 mg\/kg BW. Ten rats received saline as a control group. cTnI was measured with Access(R) (ng\/ml) and a research immunoassay (pg\/ml), and compared with cTnT, CK-MB mass and CK. By using transthoracic echocardiography, anterior and posterior wall thickness, LV diameters and LV fractional shortening (FS) were measured in all rats before DOX or saline, and at weeks 6 and 9 after treatment in all surviving rats. Histology was performed in DOX-rats at 6 and 9 weeks after the last DOX dose and in all controls. RESULTS: Eighteen of the DOX rats died prematurely of general toxicity during the 9-week period. End-diastolic (ED) and end-systolic (ES) LV diameters\/BW significantly increased, whereas LV FS was decreased after 9 weeks in the DOX group (p<0.001). These parameters remained unchanged in controls. Histological evaluation of hearts from all rats given DOX revealed significant slight degrees of perivascular and interstitial fibrosis. In 7 of the 18 rats, degeneration and myocyte vacuolisation were found. Only five of the controls exhibited evidence of very slight perivascular fibrosis. A significant rise in cTnT was found in DOX rats after cumulative doses of 7.5 and 12 mg\/kg in comparison with baseline (p<0.05). cTnT found in rats after 12 mg\/kg were significantly greater than that found after 7.5 mg\/kg DOX. Maximal cTnI (pg\/ml) and cTnT levels were significantly increased in DOX rats compared with controls (p=0.006, 0.007). cTnI (ng\/ml), CK-MB mass and CK remained unchanged in DOX rats compared with controls. All markers remained stable in controls. Analysis of data revealed a significant correlation between maximal cTnT and ED and ES LV diameters\/BW (r=0.81 and 0.65; p<0.0001). A significant relationship was observed between maximal cTnT and the extent of myocardial morphological changes, and between LV diameters\/BW and histological findings. CONCLUSIONS: Among markers of ischemic injury after DOX in rats, cTnT showed the greatest ability to detect myocardial damage assessed by echocardiographic detection and histological changes. Although there was a discrepancy between the amount of cTnI and cTnT after DOX, probably due to heterogeneity in cross-reactivities of mAbs to various cTnI and cTnT forms, it is likely that cTnT in rats after DOX indicates cell damage determined by the magnitude of injury induced and that cTnT should be a useful marker for the prediction of experimentally induced cardiotoxicity and possibly for cardioprotective experiments."],"offsets":[[195,3282]]}],"entities":[{"id":"17606","type":"Disease","text":["myocardial damage"],"offsets":[[60,77]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"17607","type":"Chemical","text":["doxorubicin"],"offsets":[[81,92]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"17608","type":"Disease","text":["cardiomyopathy"],"offsets":[[101,115]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"17609","type":"Disease","text":["myocardial cell injury"],"offsets":[[310,332]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"17610","type":"Disease","text":["myocardial damage"],"offsets":[[409,426]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"17611","type":"Chemical","text":["doxorubicin"],"offsets":[[445,456]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"17612","type":"Chemical","text":["DOX"],"offsets":[[458,461]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"17613","type":"Disease","text":["cardiomyopathy"],"offsets":[[471,485]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"17614","type":"Disease","text":["cardiac 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{"id":"17737","document_id":"11263551","passages":[{"id":"17738","type":"title","text":["Calcineurin-inhibitor induced pain syndrome (CIPS): a severe disabling complication after organ transplantation."],"offsets":[[0,112]]},{"id":"17739","type":"abstract","text":["Bone pain after transplantation is a frequent complication that can be caused by several diseases. Treatment strategies depend on the correct diagnosis of the pain. Nine patients with severe pain in their feet, which was registered after transplantation, were investigated. Bone scans showed an increased tracer uptake of the foot bones. Magnetic resonance imaging demonstrated bone marrow oedema in the painful bones. Pain was not explained by other diseases causing foot pain, like reflex sympathetic dystrophy, polyneuropathy, Morton's neuralgia, gout, osteoporosis, avascular necrosis, intermittent claudication, orthopaedic foot deformities, stress fractures, and hyperparathyroidism. The reduction of cyclosporine- or tacrolimus trough levels and the administration of calcium channel blockers led to relief of pain. The Calcineurin-inhibitor Induced Pain Syndrome (CIPS) is a rare but severe side effect of cyclosporine or tacrolimus and is accurately diagnosed by its typical presentation, magnetic resonance imaging and bone scans. Incorrect diagnosis of the syndrome will lead to a significant reduction of life quality in patients suffering from CIPS."],"offsets":[[113,1275]]}],"entities":[{"id":"17740","type":"Disease","text":["pain"],"offsets":[[30,34]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"17741","type":"Disease","text":["CIPS"],"offsets":[[45,49]],"normalized":[]},{"id":"17742","type":"Disease","text":["pain"],"offsets":[[118,122]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"17743","type":"Disease","text":["pain"],"offsets":[[272,276]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"17744","type":"Disease","text":["pain"],"offsets":[[304,308]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"17745","type":"Disease","text":["bone marrow oedema"],"offsets":[[491,509]],"normalized":[{"db_name":"MESH","db_id":"D001855"},{"db_name":"MESH","db_id":"D004487"}]},{"id":"17746","type":"Disease","text":["bone 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{"id":"17817","document_id":"10520387","passages":[{"id":"17818","type":"title","text":["The haemodynamic effects of propofol in combination with ephedrine in elderly patients (ASA groups 3 and 4)."],"offsets":[[0,108]]},{"id":"17819","type":"abstract","text":["The marked vasodilator and negative inotropic effects of propofol are disadvantages in frail elderly patients. We investigated the safety and efficacy of adding different doses of ephedrine to propofol in order to obtund the hypotensive response. The haemodynamic effects of adding 15, 20 or 25 mg of ephedrine to 200 mg of propofol were compared to control in 40 ASA 3\/4 patients over 60 years presenting for genito-urinary surgery. The addition of ephedrine to propofol appears to be an effective method of obtunding the hypotensive response to propofol at all doses used in this study. However, marked tachycardia associated with the use of ephedrine in combination with propofol occurred in the majority of patients, occasionally reaching high levels in individual patients. Due to the risk of this tachycardia inducing myocardial ischemia, we would not recommend the use in elderly patients of any of the ephedrine\/propofol\/mixtures studied."],"offsets":[[109,1055]]}],"entities":[{"id":"17820","type":"Chemical","text":["propofol"],"offsets":[[28,36]],"normalized":[{"db_name":"MESH","db_id":"D015742"}]},{"id":"17821","type":"Chemical","text":["ephedrine"],"offsets":[[57,66]],"normalized":[{"db_name":"MESH","db_id":"D004809"}]},{"id":"17822","type":"Chemical","text":["propofol"],"offsets":[[166,174]],"normalized":[{"db_name":"MESH","db_id":"D015742"}]},{"id":"17823","type":"Chemical","text":["ephedrine"],"offsets":[[289,298]],"normalized":[{"db_name":"MESH","db_id":"D004809"}]},{"id":"17824","type":"Chemical","text":["propofol"],"offsets":[[302,310]],"normalized":[{"db_name":"MESH","db_id":"D015742"}]},{"id":"17825","type":"Disease","text":["hypotensive"],"offsets":[[334,345]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"17826","type":"Chemical","text":["ephedrine"],"offsets":[[410,419]],"normalized":[{"db_name":"MESH","db_id":"D004809"}]},{"id":"17827","type":"Chemical","text":["propofol"],"offsets":[[433,441]],"normalized":[{"db_name":"MESH","db_id":"D015742"}]},{"id":"17828","type":"Chemical","text":["ephedrine"],"offsets":[[559,568]],"normalized":[{"db_name":"MESH","db_id":"D004809"}]},{"id":"17829","type":"Chemical","text":["propofol"],"offsets":[[572,580]],"normalized":[{"db_name":"MESH","db_id":"D015742"}]},{"id":"17830","type":"Disease","text":["hypotensive"],"offsets":[[632,643]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"17831","type":"Chemical","text":["propofol"],"offsets":[[656,664]],"normalized":[{"db_name":"MESH","db_id":"D015742"}]},{"id":"17832","type":"Disease","text":["tachycardia"],"offsets":[[714,725]],"normalized":[{"db_name":"MESH","db_id":"D013610"}]},{"id":"17833","type":"Chemical","text":["ephedrine"],"offsets":[[753,762]],"normalized":[{"db_name":"MESH","db_id":"D004809"}]},{"id":"17834","type":"Chemical","text":["propofol"],"offsets":[[783,791]],"normalized":[{"db_name":"MESH","db_id":"D015742"}]},{"id":"17835","type":"Disease","text":["tachycardia"],"offsets":[[912,923]],"normalized":[{"db_name":"MESH","db_id":"D013610"}]},{"id":"17836","type":"Disease","text":["myocardial ischemia"],"offsets":[[933,952]],"normalized":[{"db_name":"MESH","db_id":"D017202"}]},{"id":"17837","type":"Chemical","text":["ephedrine"],"offsets":[[1019,1028]],"normalized":[{"db_name":"MESH","db_id":"D004809"}]},{"id":"17838","type":"Chemical","text":["propofol"],"offsets":[[1029,1037]],"normalized":[{"db_name":"MESH","db_id":"D015742"}]}],"events":[],"coreferences":[],"relations":[{"id":"17839","type":"CID","arg1_id":"17820","arg2_id":"17825","normalized":[]},{"id":"17840","type":"CID","arg1_id":"17820","arg2_id":"17830","normalized":[]},{"id":"17841","type":"CID","arg1_id":"17822","arg2_id":"17825","normalized":[]},{"id":"17842","type":"CID","arg1_id":"17822","arg2_id":"17830","normalized":[]},{"id":"17843","type":"CID","arg1_id":"17824","arg2_id":"17825","normalized":[]},{"id":"17844","type":"CID","arg1_id":"17824","arg2_id":"17830","normalized":[]},{"id":"17845","type":"CID","arg1_id":"17827","arg2_id":"17825","normalized":[]},{"id":"17846","type":"CID","arg1_id":"17827","arg2_id":"17830","normalized":[]},{"id":"17847","type":"CID","arg1_id":"17829","arg2_id":"17825","normalized":[]},{"id":"17848","type":"CID","arg1_id":"17829","arg2_id":"17830","normalized":[]},{"id":"17849","type":"CID","arg1_id":"17831","arg2_id":"17825","normalized":[]},{"id":"17850","type":"CID","arg1_id":"17831","arg2_id":"17830","normalized":[]},{"id":"17851","type":"CID","arg1_id":"17834","arg2_id":"17825","normalized":[]},{"id":"17852","type":"CID","arg1_id":"17834","arg2_id":"17830","normalized":[]},{"id":"17853","type":"CID","arg1_id":"17838","arg2_id":"17825","normalized":[]},{"id":"17854","type":"CID","arg1_id":"17838","arg2_id":"17830","normalized":[]},{"id":"17855","type":"CID","arg1_id":"17820","arg2_id":"17832","normalized":[]},{"id":"17856","type":"CID","arg1_id":"17820","arg2_id":"17835","normalized":[]},{"id":"17857","type":"CID","arg1_id":"17822","arg2_id":"17832","normalized":[]},{"id":"17858","type":"CID","arg1_id":"17822","arg2_id":"17835","normalized":[]},{"id":"17859","type":"CID","arg1_id":"17824","arg2_id":"17832","normalized":[]},{"id":"17860","type":"CID","arg1_id":"17824","arg2_id":"17835","normalized":[]},{"id":"17861","type":"CID","arg1_id":"17827","arg2_id":"17832","normalized":[]},{"id":"17862","type":"CID","arg1_id":"17827","arg2_id":"17835","normalized":[]},{"id":"17863","type":"CID","arg1_id":"17829","arg2_id":"17832","normalized":[]},{"id":"17864","type":"CID","arg1_id":"17829","arg2_id":"17835","normalized":[]},{"id":"17865","type":"CID","arg1_id":"17831","arg2_id":"17832","normalized":[]},{"id":"17866","type":"CID","arg1_id":"17831","arg2_id":"17835","normalized":[]},{"id":"17867","type":"CID","arg1_id":"17834","arg2_id":"17832","normalized":[]},{"id":"17868","type":"CID","arg1_id":"17834","arg2_id":"17835","normalized":[]},{"id":"17869","type":"CID","arg1_id":"17838","arg2_id":"17832","normalized":[]},{"id":"17870","type":"CID","arg1_id":"17838","arg2_id":"17835","normalized":[]},{"id":"17871","type":"CID","arg1_id":"17821","arg2_id":"17832","normalized":[]},{"id":"17872","type":"CID","arg1_id":"17821","arg2_id":"17835","normalized":[]},{"id":"17873","type":"CID","arg1_id":"17823","arg2_id":"17832","normalized":[]},{"id":"17874","type":"CID","arg1_id":"17823","arg2_id":"17835","normalized":[]},{"id":"17875","type":"CID","arg1_id":"17826","arg2_id":"17832","normalized":[]},{"id":"17876","type":"CID","arg1_id":"17826","arg2_id":"17835","normalized":[]},{"id":"17877","type":"CID","arg1_id":"17828","arg2_id":"17832","normalized":[]},{"id":"17878","type":"CID","arg1_id":"17828","arg2_id":"17835","normalized":[]},{"id":"17879","type":"CID","arg1_id":"17833","arg2_id":"17832","normalized":[]},{"id":"17880","type":"CID","arg1_id":"17833","arg2_id":"17835","normalized":[]},{"id":"17881","type":"CID","arg1_id":"17837","arg2_id":"17832","normalized":[]},{"id":"17882","type":"CID","arg1_id":"17837","arg2_id":"17835","normalized":[]}]}
{"id":"17883","document_id":"230316","passages":[{"id":"17884","type":"title","text":["Neurotoxicity of halogenated hydroxyquinolines: clinical analysis of cases reported outside Japan."],"offsets":[[0,98]]},{"id":"17885","type":"abstract","text":["An analysis is presented of 220 cases of possible neurotoxic reactions to halogenated hydroxyquinolines reported from outside Japan. In 80 cases insufficient information was available for adequate comment and in 29 a relationship to the administration of clioquinol could be excluded. Of the remainder, a relationship to clioquinol was considered probable in 42 and possible in 69 cases. In six of the probable cases the neurological disturbance consisted of an acute reversible encephalopathy usually related to the ingestion of a high dose of clioquinol over a short period. The most common manifestation, observed in 15 further cases, was isolated optic atrophy. This was most frequently found in children, many of whom had received clioquinol as treatment for acrodermatitis enteropathica. In the remaining cases, a combination of myelopathy, visual disturbance, and peripheral neuropathy was the most common manifestation. Isolated myelopathy or peripheral neuropathy, or these manifestations occurring together, were infrequent. The onset of all manifestations (except toxic encephalopathy) was usually subacute, with subsequent partial recovery. Older subjects tended to display more side effects. The full syndrome of subacute myelo-optic neuropathy was more frequent in women, but they tended to have taken greater quantities of the drug."],"offsets":[[99,1446]]}],"entities":[{"id":"17886","type":"Disease","text":["Neurotoxicity"],"offsets":[[0,13]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"17887","type":"Chemical","text":["halogenated hydroxyquinolines"],"offsets":[[17,46]],"normalized":[{"db_name":"MESH","db_id":"D006912"}]},{"id":"17888","type":"Disease","text":["neurotoxic"],"offsets":[[149,159]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"17889","type":"Chemical","text":["halogenated hydroxyquinolines"],"offsets":[[173,202]],"normalized":[{"db_name":"MESH","db_id":"D006912"}]},{"id":"17890","type":"Chemical","text":["clioquinol"],"offsets":[[354,364]],"normalized":[{"db_name":"MESH","db_id":"D007464"}]},{"id":"17891","type":"Chemical","text":["clioquinol"],"offsets":[[420,430]],"normalized":[{"db_name":"MESH","db_id":"D007464"}]},{"id":"17892","type":"Disease","text":["neurological disturbance"],"offsets":[[520,544]],"normalized":[{"db_name":"MESH","db_id":"D009422"}]},{"id":"17893","type":"Disease","text":["encephalopathy"],"offsets":[[578,592]],"normalized":[{"db_name":"MESH","db_id":"D001927"}]},{"id":"17894","type":"Chemical","text":["clioquinol"],"offsets":[[644,654]],"normalized":[{"db_name":"MESH","db_id":"D007464"}]},{"id":"17895","type":"Disease","text":["optic atrophy"],"offsets":[[750,763]],"normalized":[{"db_name":"MESH","db_id":"D009896"}]},{"id":"17896","type":"Chemical","text":["clioquinol"],"offsets":[[835,845]],"normalized":[{"db_name":"MESH","db_id":"D007464"}]},{"id":"17897","type":"Disease","text":["acrodermatitis enteropathica"],"offsets":[[863,891]],"normalized":[{"db_name":"MESH","db_id":"C538178"}]},{"id":"17898","type":"Disease","text":["myelopathy"],"offsets":[[934,944]],"normalized":[{"db_name":"MESH","db_id":"D013118"}]},{"id":"17899","type":"Disease","text":["visual disturbance"],"offsets":[[946,964]],"normalized":[{"db_name":"MESH","db_id":"D014786"}]},{"id":"17900","type":"Disease","text":["peripheral neuropathy"],"offsets":[[970,991]],"normalized":[{"db_name":"MESH","db_id":"D010523"}]},{"id":"17901","type":"Disease","text":["myelopathy"],"offsets":[[1036,1046]],"normalized":[{"db_name":"MESH","db_id":"D013118"}]},{"id":"17902","type":"Disease","text":["peripheral neuropathy"],"offsets":[[1050,1071]],"normalized":[{"db_name":"MESH","db_id":"D010523"}]},{"id":"17903","type":"Disease","text":["encephalopathy"],"offsets":[[1180,1194]],"normalized":[{"db_name":"MESH","db_id":"D001927"}]},{"id":"17904","type":"Disease","text":["myelo-optic neuropathy"],"offsets":[[1334,1356]],"normalized":[{"db_name":"MESH","db_id":"D013118"},{"db_name":"MESH","db_id":"D009901"}]},{"id":"17905","type":"Disease","text":["myelo","neuropathy"],"offsets":[[1334,1339],[1346,1356]],"normalized":[{"db_name":"MESH","db_id":"D013118"}]},{"id":"17906","type":"Disease","text":["optic neuropathy"],"offsets":[[1340,1356]],"normalized":[{"db_name":"MESH","db_id":"D009901"}]}],"events":[],"coreferences":[],"relations":[{"id":"17907","type":"CID","arg1_id":"17890","arg2_id":"17893","normalized":[]},{"id":"17908","type":"CID","arg1_id":"17890","arg2_id":"17903","normalized":[]},{"id":"17909","type":"CID","arg1_id":"17891","arg2_id":"17893","normalized":[]},{"id":"17910","type":"CID","arg1_id":"17891","arg2_id":"17903","normalized":[]},{"id":"17911","type":"CID","arg1_id":"17894","arg2_id":"17893","normalized":[]},{"id":"17912","type":"CID","arg1_id":"17894","arg2_id":"17903","normalized":[]},{"id":"17913","type":"CID","arg1_id":"17896","arg2_id":"17893","normalized":[]},{"id":"17914","type":"CID","arg1_id":"17896","arg2_id":"17903","normalized":[]},{"id":"17915","type":"CID","arg1_id":"17890","arg2_id":"17899","normalized":[]},{"id":"17916","type":"CID","arg1_id":"17891","arg2_id":"17899","normalized":[]},{"id":"17917","type":"CID","arg1_id":"17894","arg2_id":"17899","normalized":[]},{"id":"17918","type":"CID","arg1_id":"17896","arg2_id":"17899","normalized":[]},{"id":"17919","type":"CID","arg1_id":"17890","arg2_id":"17900","normalized":[]},{"id":"17920","type":"CID","arg1_id":"17890","arg2_id":"17902","normalized":[]},{"id":"17921","type":"CID","arg1_id":"17891","arg2_id":"17900","normalized":[]},{"id":"17922","type":"CID","arg1_id":"17891","arg2_id":"17902","normalized":[]},{"id":"17923","type":"CID","arg1_id":"17894","arg2_id":"17900","normalized":[]},{"id":"17924","type":"CID","arg1_id":"17894","arg2_id":"17902","normalized":[]},{"id":"17925","type":"CID","arg1_id":"17896","arg2_id":"17900","normalized":[]},{"id":"17926","type":"CID","arg1_id":"17896","arg2_id":"17902","normalized":[]},{"id":"17927","type":"CID","arg1_id":"17890","arg2_id":"17895","normalized":[]},{"id":"17928","type":"CID","arg1_id":"17891","arg2_id":"17895","normalized":[]},{"id":"17929","type":"CID","arg1_id":"17894","arg2_id":"17895","normalized":[]},{"id":"17930","type":"CID","arg1_id":"17896","arg2_id":"17895","normalized":[]},{"id":"17931","type":"CID","arg1_id":"17890","arg2_id":"17898","normalized":[]},{"id":"17932","type":"CID","arg1_id":"17890","arg2_id":"17901","normalized":[]},{"id":"17933","type":"CID","arg1_id":"17890","arg2_id":"17904","normalized":[]},{"id":"17934","type":"CID","arg1_id":"17890","arg2_id":"17905","normalized":[]},{"id":"17935","type":"CID","arg1_id":"17891","arg2_id":"17898","normalized":[]},{"id":"17936","type":"CID","arg1_id":"17891","arg2_id":"17901","normalized":[]},{"id":"17937","type":"CID","arg1_id":"17891","arg2_id":"17904","normalized":[]},{"id":"17938","type":"CID","arg1_id":"17891","arg2_id":"17905","normalized":[]},{"id":"17939","type":"CID","arg1_id":"17894","arg2_id":"17898","normalized":[]},{"id":"17940","type":"CID","arg1_id":"17894","arg2_id":"17901","normalized":[]},{"id":"17941","type":"CID","arg1_id":"17894","arg2_id":"17904","normalized":[]},{"id":"17942","type":"CID","arg1_id":"17894","arg2_id":"17905","normalized":[]},{"id":"17943","type":"CID","arg1_id":"17896","arg2_id":"17898","normalized":[]},{"id":"17944","type":"CID","arg1_id":"17896","arg2_id":"17901","normalized":[]},{"id":"17945","type":"CID","arg1_id":"17896","arg2_id":"17904","normalized":[]},{"id":"17946","type":"CID","arg1_id":"17896","arg2_id":"17905","normalized":[]}]}
{"id":"17947","document_id":"11807648","passages":[{"id":"17948","type":"title","text":["Epileptic seizures following cortical application of fibrin sealants containing tranexamic acid in rats."],"offsets":[[0,104]]},{"id":"17949","type":"abstract","text":["BACKGROUND: Fibrin sealants (FS) derived from human plasma are frequently used in neurosurgery. In order to increase clot stability, FS typically contain aprotinin, a natural fibrinolysis inhibitor. Recently, synthetic fibrinolysis inhibitors such as tranexamic acid (tAMCA) have been considered as substitutes for aprotinin. However, tAMCA has been shown to cause epileptic seizures. We wanted to study whether tAMCA retains its convulsive action if incorporated into a FS. METHOD: FS containing aprotinin or different concentrations of tAMCA (0.5-47.5 mg\/ml) were applied to the pial surface of the cortex of anaesthetized rats. The response of the animals was evaluated using electroencephalography and by monitoring the clinical behaviour during and after recovery from anaesthesia. FINDINGS: FS containing tAMCA caused paroxysmal brain activity which was associated with distinct convulsive behaviours. The degree of these seizures increased with increasing concentration of tAMCA. Thus, FS containing 47.5 mg\/ml tAMCA evoked generalized seizures in all tested rats (n=6) while the lowest concentration of tAMCA (0.5 mg\/ml) only evoked brief episodes of jerk-correlated convulsive potentials in 1 of 6 rats. In contrast, FS containing aprotinin did not evoke any paroxysmal activity. INTERPRETATION: Tranexamic acid retains its convulsive action within FS. Thus, use of FS containing tAMCA for surgery within or close to the CNS may pose a substantial risk to the patient."],"offsets":[[105,1582]]}],"entities":[{"id":"17950","type":"Disease","text":["Epileptic seizures"],"offsets":[[0,18]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"17951","type":"Chemical","text":["tranexamic acid"],"offsets":[[80,95]],"normalized":[{"db_name":"MESH","db_id":"D014148"}]},{"id":"17952","type":"Chemical","text":["tranexamic acid"],"offsets":[[356,371]],"normalized":[{"db_name":"MESH","db_id":"D014148"}]},{"id":"17953","type":"Chemical","text":["tAMCA"],"offsets":[[373,378]],"normalized":[{"db_name":"MESH","db_id":"D014148"}]},{"id":"17954","type":"Chemical","text":["tAMCA"],"offsets":[[440,445]],"normalized":[{"db_name":"MESH","db_id":"D014148"}]},{"id":"17955","type":"Disease","text":["epileptic seizures"],"offsets":[[470,488]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"17956","type":"Chemical","text":["tAMCA"],"offsets":[[517,522]],"normalized":[{"db_name":"MESH","db_id":"D014148"}]},{"id":"17957","type":"Disease","text":["convulsive"],"offsets":[[535,545]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"17958","type":"Chemical","text":["tAMCA"],"offsets":[[643,648]],"normalized":[{"db_name":"MESH","db_id":"D014148"}]},{"id":"17959","type":"Chemical","text":["tAMCA"],"offsets":[[916,921]],"normalized":[{"db_name":"MESH","db_id":"D014148"}]},{"id":"17960","type":"Disease","text":["convulsive"],"offsets":[[990,1000]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"17961","type":"Disease","text":["seizures"],"offsets":[[1033,1041]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"17962","type":"Chemical","text":["tAMCA"],"offsets":[[1085,1090]],"normalized":[{"db_name":"MESH","db_id":"D014148"}]},{"id":"17963","type":"Chemical","text":["tAMCA"],"offsets":[[1123,1128]],"normalized":[{"db_name":"MESH","db_id":"D014148"}]},{"id":"17964","type":"Disease","text":["generalized 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17964","normalized":[]},{"id":"18028","type":"CID","arg1_id":"17965","arg2_id":"17966","normalized":[]},{"id":"18029","type":"CID","arg1_id":"17965","arg2_id":"17968","normalized":[]},{"id":"18030","type":"CID","arg1_id":"17967","arg2_id":"17957","normalized":[]},{"id":"18031","type":"CID","arg1_id":"17967","arg2_id":"17960","normalized":[]},{"id":"18032","type":"CID","arg1_id":"17967","arg2_id":"17961","normalized":[]},{"id":"18033","type":"CID","arg1_id":"17967","arg2_id":"17964","normalized":[]},{"id":"18034","type":"CID","arg1_id":"17967","arg2_id":"17966","normalized":[]},{"id":"18035","type":"CID","arg1_id":"17967","arg2_id":"17968","normalized":[]},{"id":"18036","type":"CID","arg1_id":"17969","arg2_id":"17957","normalized":[]},{"id":"18037","type":"CID","arg1_id":"17969","arg2_id":"17960","normalized":[]},{"id":"18038","type":"CID","arg1_id":"17969","arg2_id":"17961","normalized":[]},{"id":"18039","type":"CID","arg1_id":"17969","arg2_id":"17964","normalized":[]},{"id":"18040","type":"CID","arg1_id":"17969","arg2_id":"17966","normalized":[]},{"id":"18041","type":"CID","arg1_id":"17969","arg2_id":"17968","normalized":[]}]}
{"id":"18042","document_id":"14596845","passages":[{"id":"18043","type":"title","text":["A diet promoting sugar dependency causes behavioral cross-sensitization to a low dose of amphetamine."],"offsets":[[0,101]]},{"id":"18044","type":"abstract","text":["Previous research in this laboratory has shown that a diet of intermittent excessive sugar consumption produces a state with neurochemical and behavioral similarities to drug dependency. The present study examined whether female rats on various regimens of sugar access would show behavioral cross-sensitization to a low dose of amphetamine. After a 30-min baseline measure of locomotor activity (day 0), animals were maintained on a cyclic diet of 12-h deprivation followed by 12-h access to 10% sucrose solution and chow pellets (12 h access starting 4 h after onset of the dark period) for 21 days. Locomotor activity was measured again for 30 min at the beginning of days 1 and 21 of sugar access. Beginning on day 22, all rats were maintained on ad libitum chow. Nine days later locomotor activity was measured in response to a single low dose of amphetamine (0.5 mg\/kg). The animals that had experienced cyclic sucrose and chow were hyperactive in response to amphetamine compared with four control groups (ad libitum 10% sucrose and chow followed by amphetamine injection, cyclic chow followed by amphetamine injection, ad libitum chow with amphetamine, or cyclic 10% sucrose and chow with a saline injection). These results suggest that a diet comprised of alternating deprivation and access to a sugar solution and chow produces bingeing on sugar that leads to a long lasting state of increased sensitivity to amphetamine, possibly due to a lasting alteration in the dopamine system."],"offsets":[[102,1594]]}],"entities":[{"id":"18045","type":"Disease","text":["sugar dependency"],"offsets":[[17,33]],"normalized":[{"db_name":"MESH","db_id":"D019966"}]},{"id":"18046","type":"Disease","text":["behavioral cross-sensitization"],"offsets":[[41,71]],"normalized":[{"db_name":"MESH","db_id":"D006948"}]},{"id":"18047","type":"Chemical","text":["amphetamine"],"offsets":[[89,100]],"normalized":[{"db_name":"MESH","db_id":"D000661"}]},{"id":"18048","type":"Disease","text":["drug dependency"],"offsets":[[272,287]],"normalized":[{"db_name":"MESH","db_id":"D019966"}]},{"id":"18049","type":"Disease","text":["behavioral 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{"id":"18099","document_id":"6666578","passages":[{"id":"18100","type":"title","text":["D-penicillamine-induced angiopathy in rats. The effect of high dose D-penicillamine treatment on aortic permeability to albumin and on the ultrastructure of the vessel."],"offsets":[[0,168]]},{"id":"18101","type":"abstract","text":["Male Sprague-Dawley rats were treated with D-penicillamine (D-pen) 500 mg\/kg\/day for 10 or 42 days. Pair fed rats served as controls. Changes in aortic morphology were examined by light- and transmission-electron microscopy (TEM). In addition, the endothelial permeability and the penetration through the aortic wall of albumin were studied 10 minutes, 24 and 48 hours after i. v. injection of human serum 131I-albumin (131I-HSA). TEM revealed extensive elastolysis in the arterial wall of D-pen-treated rats, consistent with an inhibitory effect on crosslink formation. In experimental animals excess deposition of collagen and glycoaminoglycans was observed in the subendothelial and medial layer of the aortic wall, together with prominent basal membrane substance around aortic smooth muscle cells. The aorta\/serum-ratio and the radioactive build-up 24 and 48 hours after injection of 131I-HSA was reduced in animals treated with D-pen for 42 days, indicating an impeded transmural transport of tracer which may be caused by a steric exclusion effect of abundant hyaluronate. The endothelial ultrastructure was unaffected by D-pen, and no differences in aortic 131I-HSA radioactivity or aorta\/serum-ratio were recorded between experimental and control groups 10 minutes after tracer injection, indicating that the permeability of the endothelial barrier to albumin remained unaffected by D-pen treatment. These observations support the hypothesis that treatment with high doses of D-pen may induce a fibroproliferative response in rat aorta, possibly by an inhibitory effect on the cross-linking of collagen and elastin."],"offsets":[[169,1793]]}],"entities":[{"id":"18102","type":"Chemical","text":["D-penicillamine"],"offsets":[[0,15]],"normalized":[{"db_name":"MESH","db_id":"D010396"}]},{"id":"18103","type":"Disease","text":["angiopathy"],"offsets":[[24,34]],"normalized":[{"db_name":"MESH","db_id":"D001018"}]},{"id":"18104","type":"Chemical","text":["D-penicillamine"],"offsets":[[68,83]],"normalized":[{"db_name":"MESH","db_id":"D010396"}]},{"id":"18105","type":"Chemical","text":["D-penicillamine"],"offsets":[[212,227]],"normalized":[{"db_name":"MESH","db_id":"D010396"}]},{"id":"18106","type":"Chemical","text":["D-pen"],"offsets":[[229,234]],"normalized":[{"db_name":"MESH","db_id":"D010396"}]},{"id":"18107","type":"Chemical","text":["D-pen"],"offsets":[[659,664]],"normalized":[{"db_name":"MESH","db_id":"D010396"}]},{"id":"18108","type":"Chemical","text":["D-pen"],"offsets":[[1103,1108]],"normalized":[{"db_name":"MESH","db_id":"D010396"}]},{"id":"18109","type":"Chemical","text":["hyaluronate"],"offsets":[[1236,1247]],"normalized":[{"db_name":"MESH","db_id":"D006820"}]},{"id":"18110","type":"Chemical","text":["D-pen"],"offsets":[[1298,1303]],"normalized":[{"db_name":"MESH","db_id":"D010396"}]},{"id":"18111","type":"Chemical","text":["D-pen"],"offsets":[[1561,1566]],"normalized":[{"db_name":"MESH","db_id":"D010396"}]},{"id":"18112","type":"Chemical","text":["D-pen"],"offsets":[[1654,1659]],"normalized":[{"db_name":"MESH","db_id":"D010396"}]}],"events":[],"coreferences":[],"relations":[{"id":"18113","type":"CID","arg1_id":"18102","arg2_id":"18103","normalized":[]},{"id":"18114","type":"CID","arg1_id":"18104","arg2_id":"18103","normalized":[]},{"id":"18115","type":"CID","arg1_id":"18105","arg2_id":"18103","normalized":[]},{"id":"18116","type":"CID","arg1_id":"18106","arg2_id":"18103","normalized":[]},{"id":"18117","type":"CID","arg1_id":"18107","arg2_id":"18103","normalized":[]},{"id":"18118","type":"CID","arg1_id":"18108","arg2_id":"18103","normalized":[]},{"id":"18119","type":"CID","arg1_id":"18110","arg2_id":"18103","normalized":[]},{"id":"18120","type":"CID","arg1_id":"18111","arg2_id":"18103","normalized":[]},{"id":"18121","type":"CID","arg1_id":"18112","arg2_id":"18103","normalized":[]}]}
{"id":"18122","document_id":"11279304","passages":[{"id":"18123","type":"title","text":["Brain natriuretic peptide is a predictor of anthracycline-induced cardiotoxicity."],"offsets":[[0,81]]},{"id":"18124","type":"abstract","text":["Anthracyclines are effective antineoplastic drugs, but they frequently cause dose-related cardiotoxicity. The cardiotoxicity of conventional anthracycline therapy highlights a need to search for methods that are highly sensitive and capable of predicting cardiac dysfunction. We measured the plasma level of brain natriuretic peptide (BNP) to determine whether BNP might serve as a simple diagnostic indicator of anthracycline-induced cardiotoxicity in patients with acute leukemia treated with a daunorubicin (DNR)-containing regimen. Thirteen patients with acute leukemia were treated with a DNR-containing regimen. Cardiac functions were evaluated with radionuclide angiography before chemotherapies. The plasma levels of atrial natriuretic peptide (ANP) and BNP were measured at the time of radionuclide angiography. Three patients developed congestive heart failure after the completion of chemotherapy. Five patients were diagnosed as having subclinical heart failure after the completion of chemotherapy. The plasma levels of BNP in all the patients with clinical and subclinical heart failure increased above the normal limit (40 pg\/ml) before the detection of clinical or subclinical heart failure by radionuclide angiography. On the other hand, BNP did not increase in the patients without heart failure given DNR, even at more than 700 mg\/m(2). The plasma level of ANP did not always increase in all the patients with clinical and subclinical heart failure. These preliminary results suggest that BNP may be useful as an early and sensitive indicator of anthracycline-induced cardiotoxicity."],"offsets":[[82,1684]]}],"entities":[{"id":"18125","type":"Chemical","text":["anthracycline"],"offsets":[[44,57]],"normalized":[{"db_name":"MESH","db_id":"D018943"}]},{"id":"18126","type":"Disease","text":["cardiotoxicity"],"offsets":[[66,80]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"18127","type":"Chemical","text":["Anthracyclines"],"offsets":[[82,96]],"normalized":[{"db_name":"MESH","db_id":"D018943"}]},{"id":"18128","type":"Disease","text":["cardiotoxicity"],"offsets":[[172,186]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"18129","type":"Disease","text":["cardiotoxicity"],"offsets":[[192,206]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"18130","type":"Chemical","text":["anthracycline"],"offsets":[[223,236]],"normalized":[{"db_name":"MESH","db_id":"D018943"}]},{"id":"18131","type":"Disease","text":["cardiac dysfunction"],"offsets":[[337,356]],"normalized":[{"db_name":"MESH","db_id":"D006331"}]},{"id":"18132","type":"Chemical","text":["anthracycline"],"offsets":[[495,508]],"normalized":[{"db_name":"MESH","db_id":"D018943"}]},{"id":"18133","type":"Disease","text":["cardiotoxicity"],"offsets":[[517,531]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"18134","type":"Disease","text":["acute leukemia"],"offsets":[[549,563]],"normalized":[{"db_name":"MESH","db_id":"D015470"}]},{"id":"18135","type":"Chemical","text":["daunorubicin"],"offsets":[[579,591]],"normalized":[{"db_name":"MESH","db_id":"D003630"}]},{"id":"18136","type":"Chemical","text":["DNR"],"offsets":[[593,596]],"normalized":[{"db_name":"MESH","db_id":"D003630"}]},{"id":"18137","type":"Disease","text":["acute leukemia"],"offsets":[[641,655]],"normalized":[{"db_name":"MESH","db_id":"D015470"}]},{"id":"18138","type":"Chemical","text":["DNR"],"offsets":[[676,679]],"normalized":[{"db_name":"MESH","db_id":"D003630"}]},{"id":"18139","type":"Disease","text":["congestive heart failure"],"offsets":[[928,952]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]},{"id":"18140","type":"Disease","text":["heart failure"],"offsets":[[1042,1055]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]},{"id":"18141","type":"Disease","text":["heart failure"],"offsets":[[1169,1182]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]},{"id":"18142","type":"Disease","text":["heart failure"],"offsets":[[1275,1288]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]},{"id":"18143","type":"Disease","text":["heart 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failure"],"offsets":[[1536,1549]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]},{"id":"18146","type":"Chemical","text":["anthracycline"],"offsets":[[1647,1660]],"normalized":[{"db_name":"MESH","db_id":"D018943"}]},{"id":"18147","type":"Disease","text":["cardiotoxicity"],"offsets":[[1669,1683]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]}],"events":[],"coreferences":[],"relations":[{"id":"18148","type":"CID","arg1_id":"18135","arg2_id":"18139","normalized":[]},{"id":"18149","type":"CID","arg1_id":"18135","arg2_id":"18140","normalized":[]},{"id":"18150","type":"CID","arg1_id":"18135","arg2_id":"18141","normalized":[]},{"id":"18151","type":"CID","arg1_id":"18135","arg2_id":"18142","normalized":[]},{"id":"18152","type":"CID","arg1_id":"18135","arg2_id":"18143","normalized":[]},{"id":"18153","type":"CID","arg1_id":"18135","arg2_id":"18145","normalized":[]},{"id":"18154","type":"CID","arg1_id":"18136","arg2_id":"18139","normalized":[]},{"id":"18155","type":"CID","arg1_id":"18136","arg2_id":"18140","normalized":[]},{"id":"18156","type":"CID","arg1_id":"18136","arg2_id":"18141","normalized":[]},{"id":"18157","type":"CID","arg1_id":"18136","arg2_id":"18142","normalized":[]},{"id":"18158","type":"CID","arg1_id":"18136","arg2_id":"18143","normalized":[]},{"id":"18159","type":"CID","arg1_id":"18136","arg2_id":"18145","normalized":[]},{"id":"18160","type":"CID","arg1_id":"18138","arg2_id":"18139","normalized":[]},{"id":"18161","type":"CID","arg1_id":"18138","arg2_id":"18140","normalized":[]},{"id":"18162","type":"CID","arg1_id":"18138","arg2_id":"18141","normalized":[]},{"id":"18163","type":"CID","arg1_id":"18138","arg2_id":"18142","normalized":[]},{"id":"18164","type":"CID","arg1_id":"18138","arg2_id":"18143","normalized":[]},{"id":"18165","type":"CID","arg1_id":"18138","arg2_id":"18145","normalized":[]},{"id":"18166","type":"CID","arg1_id":"18144","arg2_id":"18139","normalized":[]},{"id":"18167","type":"CID","arg1_id":"18144","arg2_id":"18140","normalized":[]},{"id":"18168","type":"CID","arg1_id":"18144","arg2_id":"18141","normalized":[]},{"id":"18169","type":"CID","arg1_id":"18144","arg2_id":"18142","normalized":[]},{"id":"18170","type":"CID","arg1_id":"18144","arg2_id":"18143","normalized":[]},{"id":"18171","type":"CID","arg1_id":"18144","arg2_id":"18145","normalized":[]}]}
{"id":"18172","document_id":"19884587","passages":[{"id":"18173","type":"title","text":["Antibacterial medication use during pregnancy and risk of birth defects: National Birth Defects Prevention Study."],"offsets":[[0,113]]},{"id":"18174","type":"abstract","text":["OBJECTIVE: To estimate the association between antibacterial medications and selected birth defects. DESIGN, SETTING, AND PARTICIPANTS: Population-based, multisite, case-control study of women who had pregnancies affected by 1 of more than 30 eligible major birth defects identified via birth defect surveillance programs in 10 states (n = 13 155) and control women randomly selected from the same geographical regions (n = 4941). MAIN EXPOSURE: Reported maternal use of antibacterials (1 month before pregnancy through the end of the first trimester). MAIN OUTCOME MEASURE: Odds ratios (ORs) measuring the association between antibacterial use and selected birth defects adjusted for potential confounders. RESULTS: The reported use of antibacterials increased during pregnancy, peaking during the third month. Sulfonamides were associated with anencephaly (adjusted OR [AOR] = 3.4; 95% confidence interval [CI], 1.3-8.8), hypoplastic left heart syndrome (AOR = 3.2; 95% CI, 1.3-7.6), coarctation of the aorta (AOR = 2.7; 95% CI, 1.3-5.6), choanal atresia (AOR = 8.0; 95% CI, 2.7-23.5), transverse limb deficiency (AOR = 2.5; 95% CI, 1.0-5.9), and diaphragmatic hernia (AOR = 2.4; 95% CI, 1.1-5.4). Nitrofurantoins were associated with anophthalmia or microphthalmos (AOR = 3.7; 95% CI, 1.1-12.2), hypoplastic left heart syndrome (AOR = 4.2; 95% CI, 1.9-9.1), atrial septal defects (AOR = 1.9; 95% CI, 1.1-3.4), and cleft lip with cleft palate (AOR = 2.1; 95% CI, 1.2-3.9). Other antibacterial agents that showed associations included erythromycins (2 defects), penicillins (1 defect), cephalosporins (1 defect), and quinolones (1 defect). CONCLUSIONS: Reassuringly, penicillins, erythromycins, and cephalosporins, although used commonly by pregnant women, were not associated with many birth defects. Sulfonamides and nitrofurantoins were associated with several birth defects, indicating a need for additional scrutiny."],"offsets":[[114,2036]]}],"entities":[{"id":"18175","type":"Disease","text":["birth defects"],"offsets":[[58,71]],"normalized":[{"db_name":"MESH","db_id":"D000014"}]},{"id":"18176","type":"Disease","text":["Birth Defects"],"offsets":[[82,95]],"normalized":[{"db_name":"MESH","db_id":"D000014"}]},{"id":"18177","type":"Disease","text":["birth defects"],"offsets":[[200,213]],"normalized":[{"db_name":"MESH","db_id":"D000014"}]},{"id":"18178","type":"Disease","text":["birth defects"],"offsets":[[372,385]],"normalized":[{"db_name":"MESH","db_id":"D000014"}]},{"id":"18179","type":"Disease","text":["birth defect"],"offsets":[[401,413]],"normalized":[{"db_name":"MESH","db_id":"D000014"}]},{"id":"18180","type":"Disease","text":["birth 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hernia"],"offsets":[[1263,1283]],"normalized":[{"db_name":"MESH","db_id":"D006548"}]},{"id":"18188","type":"Chemical","text":["Nitrofurantoins"],"offsets":[[1314,1329]],"normalized":[{"db_name":"MESH","db_id":"D009582"}]},{"id":"18189","type":"Disease","text":["anophthalmia"],"offsets":[[1351,1363]],"normalized":[{"db_name":"MESH","db_id":"D000853"}]},{"id":"18190","type":"Disease","text":["microphthalmos"],"offsets":[[1367,1381]],"normalized":[{"db_name":"MESH","db_id":"D008850"}]},{"id":"18191","type":"Disease","text":["hypoplastic left heart syndrome"],"offsets":[[1413,1444]],"normalized":[{"db_name":"MESH","db_id":"D018636"}]},{"id":"18192","type":"Disease","text":["atrial septal defects"],"offsets":[[1475,1496]],"normalized":[{"db_name":"MESH","db_id":"D006344"}]},{"id":"18193","type":"Disease","text":["cleft lip"],"offsets":[[1531,1540]],"normalized":[{"db_name":"MESH","db_id":"D002971"}]},{"id":"18194","type":"Disease","text":["cleft 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{"id":"18266","document_id":"3970039","passages":[{"id":"18267","type":"title","text":["Incidence of neoplasms in patients with rheumatoid arthritis exposed to different treatment regimens."],"offsets":[[0,101]]},{"id":"18268","type":"abstract","text":["Immunosuppressive drugs have been used during the last 30 years in treatment of patients with severe rheumatoid arthritis. The drugs commonly used are cyclophosphamide and chlorambucil (alkylating agents), azathioprine (purine analogue), and methotrexate (folic acid analogue). There is evidence that all four immunosuppressive drugs can reduce synovitis, but disease activity almost always recurs after therapy is stopped. Since adverse reactions are frequent, less than 50 percent of patients are able to continue a particular drug for more than one year. Since it takes three to 12 months to achieve maximal effects, those patients who are unable to continue the drug receive little benefit from it. Patients treated with alkylating agents have an increased risk of development of acute nonlymphocytic leukemia, and both alkylating agents and azathioprine are associated with the development of non-Hodgkin's lymphoma. Cyclophosphamide therapy increases the risk of carcinoma of the bladder. There have been several long-term studies of patients with rheumatoid arthritis treated with azathioprine and cyclophosphamide and the incidence of most of the common cancers is not increased. Data on the possible increased risk of malignancy in rheumatoid arthritis are still being collected, and until further information is available, the use of immunosuppressive drugs, particularly alkylating agents, in the treatment of rheumatoid arthritis should be reserved for patients with severe progressive disease or life-threatening complications."],"offsets":[[102,1642]]}],"entities":[{"id":"18269","type":"Disease","text":["neoplasms"],"offsets":[[13,22]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"18270","type":"Disease","text":["rheumatoid arthritis"],"offsets":[[40,60]],"normalized":[{"db_name":"MESH","db_id":"D001172"}]},{"id":"18271","type":"Disease","text":["rheumatoid 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arthritis"],"offsets":[[1523,1543]],"normalized":[{"db_name":"MESH","db_id":"D001172"}]}],"events":[],"coreferences":[],"relations":[{"id":"18297","type":"CID","arg1_id":"18274","arg2_id":"18281","normalized":[]},{"id":"18298","type":"CID","arg1_id":"18280","arg2_id":"18281","normalized":[]},{"id":"18299","type":"CID","arg1_id":"18282","arg2_id":"18281","normalized":[]},{"id":"18300","type":"CID","arg1_id":"18295","arg2_id":"18281","normalized":[]},{"id":"18301","type":"CID","arg1_id":"18272","arg2_id":"18286","normalized":[]},{"id":"18302","type":"CID","arg1_id":"18272","arg2_id":"18287","normalized":[]},{"id":"18303","type":"CID","arg1_id":"18285","arg2_id":"18286","normalized":[]},{"id":"18304","type":"CID","arg1_id":"18285","arg2_id":"18287","normalized":[]},{"id":"18305","type":"CID","arg1_id":"18291","arg2_id":"18286","normalized":[]},{"id":"18306","type":"CID","arg1_id":"18291","arg2_id":"18287","normalized":[]},{"id":"18307","type":"CID","arg1_id":"18274","arg2_id":"18284","normalized":[]},{"id":"18308","type":"CID","arg1_id":"18280","arg2_id":"18284","normalized":[]},{"id":"18309","type":"CID","arg1_id":"18282","arg2_id":"18284","normalized":[]},{"id":"18310","type":"CID","arg1_id":"18295","arg2_id":"18284","normalized":[]},{"id":"18311","type":"CID","arg1_id":"18275","arg2_id":"18284","normalized":[]},{"id":"18312","type":"CID","arg1_id":"18283","arg2_id":"18284","normalized":[]},{"id":"18313","type":"CID","arg1_id":"18290","arg2_id":"18284","normalized":[]},{"id":"18314","type":"CID","arg1_id":"18272","arg2_id":"18286","normalized":[]},{"id":"18315","type":"CID","arg1_id":"18272","arg2_id":"18288","normalized":[]},{"id":"18316","type":"CID","arg1_id":"18285","arg2_id":"18286","normalized":[]},{"id":"18317","type":"CID","arg1_id":"18285","arg2_id":"18288","normalized":[]},{"id":"18318","type":"CID","arg1_id":"18291","arg2_id":"18286","normalized":[]},{"id":"18319","type":"CID","arg1_id":"18291","arg2_id":"18288","normalized":[]}]}
{"id":"18320","document_id":"424937","passages":[{"id":"18321","type":"title","text":["Patterns of hepatic injury induced by methyldopa."],"offsets":[[0,49]]},{"id":"18322","type":"abstract","text":["Twelve patients with liver disease related to methyldopa were seen between 1967 and 1977. Illness occurred within 1--9 weeks of commencement of therapy in 9 patients, the remaining 3 patients having received the drug for 13 months, 15 months and 7 years before experiencing symptoms. Jaundice with tender hepatomegaly, usually preceded by symptoms of malaise, anorexia, nausea and vomiting, and associated with upper abdominal pain, was an invariable finding in all patients. Biochemical liver function tests indicated hepatocellular necrosis and correlated with histopathological evidence of hepatic injury, the spectrum of which ranged from fatty change and focal hepatocellular necrosis to massive hepatic necrosis. Most patients showed moderate to severe acute hepatitis or chronic active hepatitis with associated cholestasis. The drug was withdrawn on presentation to hospital in 11 patients, with rapid clinical improvement in 9. One patient died, having presented in hepatic failure, and another, who had been taking methyldopa for 7 years, showed slower clinical and biochemical resolution over a period of several months. The remaining patient in the series developed fulminant hepatitis when the drug was accidentally recommenced 1 year after a prior episode of methyldopa-induced hepatitis. In this latter patient, and in 2 others, the causal relationship between methyldopa and hepatic dysfunction was proved with the recurrence of hepatitis within 2 weeks of re-exposure to the drug."],"offsets":[[50,1547]]}],"entities":[{"id":"18323","type":"Disease","text":["hepatic injury"],"offsets":[[12,26]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"18324","type":"Chemical","text":["methyldopa"],"offsets":[[38,48]],"normalized":[{"db_name":"MESH","db_id":"D008750"}]},{"id":"18325","type":"Disease","text":["liver 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hepatitis"],"offsets":[[828,852]],"normalized":[{"db_name":"MESH","db_id":"D006521"}]},{"id":"18340","type":"Disease","text":["cholestasis"],"offsets":[[869,880]],"normalized":[{"db_name":"MESH","db_id":"D002779"}]},{"id":"18341","type":"Disease","text":["hepatic failure"],"offsets":[[1025,1040]],"normalized":[{"db_name":"MESH","db_id":"D017093"}]},{"id":"18342","type":"Chemical","text":["methyldopa"],"offsets":[[1075,1085]],"normalized":[{"db_name":"MESH","db_id":"D008750"}]},{"id":"18343","type":"Disease","text":["fulminant hepatitis"],"offsets":[[1228,1247]],"normalized":[{"db_name":"MESH","db_id":"D017114"}]},{"id":"18344","type":"Chemical","text":["methyldopa"],"offsets":[[1323,1333]],"normalized":[{"db_name":"MESH","db_id":"D008750"}]},{"id":"18345","type":"Disease","text":["hepatitis"],"offsets":[[1342,1351]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"18346","type":"Chemical","text":["methyldopa"],"offsets":[[1426,1436]],"normalized":[{"db_name":"MESH","db_id":"D008750"}]},{"id":"18347","type":"Disease","text":["hepatic 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ype":"CID","arg1_id":"18344","arg2_id":"18345","normalized":[]},{"id":"18409","type":"CID","arg1_id":"18344","arg2_id":"18348","normalized":[]},{"id":"18410","type":"CID","arg1_id":"18346","arg2_id":"18323","normalized":[]},{"id":"18411","type":"CID","arg1_id":"18346","arg2_id":"18334","normalized":[]},{"id":"18412","type":"CID","arg1_id":"18346","arg2_id":"18345","normalized":[]},{"id":"18413","type":"CID","arg1_id":"18346","arg2_id":"18348","normalized":[]},{"id":"18414","type":"CID","arg1_id":"18324","arg2_id":"18329","normalized":[]},{"id":"18415","type":"CID","arg1_id":"18326","arg2_id":"18329","normalized":[]},{"id":"18416","type":"CID","arg1_id":"18342","arg2_id":"18329","normalized":[]},{"id":"18417","type":"CID","arg1_id":"18344","arg2_id":"18329","normalized":[]},{"id":"18418","type":"CID","arg1_id":"18346","arg2_id":"18329","normalized":[]}]}
{"id":"18419","document_id":"8643971","passages":[{"id":"18420","type":"title","text":["A phase I\/II study of paclitaxel plus cisplatin as first-line therapy for head and neck cancers: preliminary results."],"offsets":[[0,117]]},{"id":"18421","type":"abstract","text":["Improved outcomes among patients with head and neck carcinomas require investigations of new drugs for induction therapy. Preliminary results of an Eastern Cooperative Oncology Group study of single-agent paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) reported a 37% response rate in patients with head and neck cancer, and the paclitaxel\/cisplatin combination has been used successfully and has significantly improved median response duration in ovarian cancer patients. We initiated a phase I\/II trial to determine the response and toxicity of escalating paclitaxel doses combined with fixed-dose cisplatin with granulocyte colony-stimulating factor support in patients with untreated locally advanced inoperable head and neck carcinoma. To date, 23 men with a median age of 50 years and good performance status have entered the trial. Primary tumor sites were oropharynx, 10 patients; hypopharynx, four; larynx, two; oral cavity, three; unknown primary, two; and nasal cavity and parotid gland, one each. Of 20 patients evaluable for toxicity, four had stage III and 16 had stage IV disease. Treatment, given every 21 days for a maximum of three cycles, consisted of paclitaxel by 3-hour infusion followed the next day by a fixed dose of cisplatin (75 mg\/m2). The dose levels incorporate escalating paclitaxel doses, and intrapatient escalations within a given dose level are permitted if toxicity permits. At the time of this writing, dose level 4 (260, 270, and 280 mg\/m2) is being evaluated; three patients from this level are evaluable. With paclitaxel doses of 200 mg\/m2 and higher, granulocyte colony-stimulating factor 5 micrograms\/kg\/d is given (days 4 through 12). Of 18 patients evaluable for response, seven (39%) achieved a complete response and six (33%) achieved a partial response. Three patients had no change and disease progressed in two. The overall response rate is 72%. Eleven responding patients had subsequent surgery\/radiotherapy or radical radiotherapy. Two pathologic complete responses were observed in patients who had achieved clinical complete responses. Alopecia, paresthesias, and arthralgias\/myalgias have occurred frequently, but with one exception (a grade 3 myalgia) they have been grade 1 or 2. No dose-limiting hematologic toxicity has been seen. Paclitaxel\/cisplatin is an effective first-line regimen for locoregionally advanced head and neck cancer and continued study is warranted. Results thus far suggest no dose-response effect for paclitaxel doses above 200 mg\/m2."],"offsets":[[118,2648]]}],"entities":[{"id":"18422","type":"Chemical","text":["paclitaxel"],"offsets":[[22,32]],"normalized":[{"db_name":"MESH","db_id":"D017239"}]},{"id":"18423","type":"Chemical","text":["cisplatin"],"offsets":[[38,47]],"normalized":[{"db_name":"MESH","db_id":"D002945"}]},{"id":"18424","type":"Disease","text":["head and neck cancers"],"offsets":[[74,95]],"normalized":[{"db_name":"MESH","db_id":"D006258"}]},{"id":"18425","type":"Disease","text":["head and neck carcinomas"],"offsets":[[156,180]],"normalized":[{"db_name":"MESH","db_id":"D006258"}]},{"id":"18426","type":"Chemical","text":["paclitaxel"],"offsets":[[323,333]],"normalized":[{"db_name":"MESH","db_id":"D017239"}]},{"id":"18427","type":"Chemical","text":["Taxol"],"offsets":[[335,340]],"normalized":[{"db_name":"MESH","db_id":"D017239"}]},{"id":"18428","type":"Disease","text":["head and neck 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and neck cancer"],"offsets":[[2507,2527]],"normalized":[{"db_name":"MESH","db_id":"D006258"}]},{"id":"18452","type":"Chemical","text":["paclitaxel"],"offsets":[[2615,2625]],"normalized":[{"db_name":"MESH","db_id":"D017239"}]}],"events":[],"coreferences":[],"relations":[{"id":"18453","type":"CID","arg1_id":"18423","arg2_id":"18443","normalized":[]},{"id":"18454","type":"CID","arg1_id":"18430","arg2_id":"18443","normalized":[]},{"id":"18455","type":"CID","arg1_id":"18434","arg2_id":"18443","normalized":[]},{"id":"18456","type":"CID","arg1_id":"18439","arg2_id":"18443","normalized":[]},{"id":"18457","type":"CID","arg1_id":"18450","arg2_id":"18443","normalized":[]},{"id":"18458","type":"CID","arg1_id":"18422","arg2_id":"18444","normalized":[]},{"id":"18459","type":"CID","arg1_id":"18426","arg2_id":"18444","normalized":[]},{"id":"18460","type":"CID","arg1_id":"18427","arg2_id":"18444","normalized":[]},{"id":"18461","type":"CID","arg1_id":"18429","arg2_id":"18444","normalized":[]},{"id":"18462","type":"CID","arg1_id":"18433","arg2_id":"18444","normalized":[]},{"id":"18463","type":"CID","arg1_id":"18438","arg2_id":"18444","normalized":[]},{"id":"18464","type":"CID","arg1_id":"18440","arg2_id":"18444","normalized":[]},{"id":"18465","type":"CID","arg1_id":"18442","arg2_id":"18444","normalized":[]},{"id":"18466","type":"CID","arg1_id":"18449","arg2_id":"18444","normalized":[]},{"id":"18467","type":"CID","arg1_id":"18452","arg2_id":"18444","normalized":[]},{"id":"18468","type":"CID","arg1_id":"18422","arg2_id":"18443","normalized":[]},{"id":"18469","type":"CID","arg1_id":"18426","arg2_id":"18443","normalized":[]},{"id":"18470","type":"CID","arg1_id":"18427","arg2_id":"18443","normalized":[]},{"id":"18471","type":"CID","arg1_id":"18429","arg2_id":"18443","normalized":[]},{"id":"18472","type":"CID","arg1_id":"18433","arg2_id":"18443","normalized":[]},{"id":"18473","type":"CID","arg1_id":"18438","arg2_id":"18443","normalized":[]},{"id":"18474","type":"CID","arg1_id":"18440","arg2_id":"18443","normalized":[]},{"id":"18475","type":"CID","arg1_id":"18442","arg2_id":"18443","normalized":[]},{"id":"18476","type":"CID","arg1_id":"18449","arg2_id":"18443","normalized":[]},{"id":"18477","type":"CID","arg1_id":"18452","arg2_id":"18443","normalized":[]},{"id":"18478","type":"CID","arg1_id":"18423","arg2_id":"18445","normalized":[]},{"id":"18479","type":"CID","arg1_id":"18430","arg2_id":"18445","normalized":[]},{"id":"18480","type":"CID","arg1_id":"18434","arg2_id":"18445","normalized":[]},{"id":"18481","type":"CID","arg1_id":"18439","arg2_id":"18445","normalized":[]},{"id":"18482","type":"CID","arg1_id":"18450","arg2_id":"18445","normalized":[]},{"id":"18483","type":"CID","arg1_id":"18422","arg2_id":"18445","normalized":[]},{"id":"18484","type":"CID","arg1_id":"18426","arg2_id":"18445","normalized":[]},{"id":"18485","type":"CID","arg1_id":"18427","arg2_id":"18445","normalized":[]},{"id":"18486","type":"CID","arg1_id":"18429","arg2_id":"18445","normalized":[]},{"id":"18487","type":"CID","arg1_id":"18433","arg2_id":"18445","normalized":[]},{"id":"18488","type":"CID","arg1_id":"18438","arg2_id":"18445","normalized":[]},{"id":"18489","type":"CID","arg1_id":"18440","arg2_id":"18445","normalized":[]},{"id":"18490","type":"CID","arg1_id":"18442","arg2_id":"18445","normalized":[]},{"id":"18491","type":"CID","arg1_id":"18449","arg2_id":"18445","normalized":[]},{"id":"18492","type":"CID","arg1_id":"18452","arg2_id":"18445","normalized":[]},{"id":"18493","type":"CID","arg1_id":"18423","arg2_id":"18444","normalized":[]},{"id":"18494","type":"CID","arg1_id":"18430","arg2_id":"18444","normalized":[]},{"id":"18495","type":"CID","arg1_id":"18434","arg2_id":"18444","normalized":[]},{"id":"18496","type":"CID","arg1_id":"18439","arg2_id":"18444","normalized":[]},{"id":"18497","type":"CID","arg1_id":"18450","arg2_id":"18444","normalized":[]}]}
{"id":"18498","document_id":"2224762","passages":[{"id":"18499","type":"title","text":["A phase I study of 4'-0-tetrahydropyranyladriamycin. Clinical pharmacology and pharmacokinetics."],"offsets":[[0,96]]},{"id":"18500","type":"abstract","text":["A Phase I study of intravenous (IV) bolus 4'-0-tetrahydropyranyladriamycin (Pirarubicin) was done in 55 patients in good performance status with refractory tumors. Twenty-six had minimal prior therapy (good risk), 23 had extensive prior therapy (poor risk), and six had renal and\/or hepatic dysfunction. A total of 167 courses at doses of 15 to 70 mg\/m2 were evaluable. Maximum tolerated dose in good-risk patients was 70 mg\/m2, and in poor-risk patients, 60 mg\/m2. The dose-limiting toxic effect was transient noncumulative granulocytopenia. Granulocyte nadir was on day 14 (range, 4-22). Less frequent toxic effects included thrombocytopenia, anemia, nausea, mild alopecia, phlebitis, and mucositis. Myelosuppression was more in patients with hepatic dysfunction. Pharmacokinetic analyses in 21 patients revealed Pirarubicin plasma T 1\/2 alpha (+\/- SE) of 2.5 +\/- 0.85 minutes, T beta 1\/2 of 25.6 +\/- 6.5 minutes, and T 1\/2 gamma of 23.6 +\/- 7.6 hours. The area under the curve was 537 +\/- 149 ng\/ml x hours, volume of distribution (Vd) 3504 +\/- 644 l\/m2, and total clearance (ClT) was 204 + 39.3 l\/hour\/m2. Adriamycinol, doxorubicin, adriamycinone, and tetrahydropyranyladriamycinol were the metabolites detected in plasma and the amount of doxorubicin was less than or equal to 10% of the total metabolites. Urinary excretion of Pirarubicin in the first 24 hours was less than or equal to 10%. Activity was noted in mesothelioma, leiomyosarcoma, and basal cell carcinoma. The recommended starting dose for Phase II trials is 60 mg\/m2 IV bolus every 3 weeks."],"offsets":[[97,1658]]}],"entities":[{"id":"18501","type":"Chemical","text":["4'-0-tetrahydropyranyladriamycin"],"offsets":[[19,51]],"normalized":[{"db_name":"MESH","db_id":"C027260"}]},{"id":"18502","type":"Chemical","text":["4'-0-tetrahydropyranyladriamycin"],"offsets":[[139,171]],"normalized":[{"db_name":"MESH","db_id":"C027260"}]},{"id":"18503","type":"Chemical","text":["Pirarubicin"],"offsets":[[173,184]],"normalized":[{"db_name":"MESH","db_id":"C027260"}]},{"id":"18504","type":"Disease","text":["tumors"],"offsets":[[253,259]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"18505","type":"Disease","text":["renal and\/or hepatic dysfunction"],"offsets":[[367,399]],"normalized":[{"db_name":"MESH","db_id":"D007674"},{"db_name":"MESH","db_id":"D008107"}]},{"id":"18506","type":"Disease","text":["renal","dysfunction"],"offsets":[[367,372],[388,399]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"18507","type":"Disease","text":["hepatic dysfunction"],"offsets":[[380,399]],"normalized":[{"db_name":"MESH","db_id":"D008107"}]},{"id":"18508","type":"Disease","text":["granulocytopenia"],"offsets":[[622,638]],"normalized":[{"db_name":"MESH","db_id":"D000380"}]},{"id":"18509","type":"Disease","text":["thrombocytopenia"],"offsets":[[724,740]],"normalized":[{"db_name":"MESH","db_id":"D013921"}]},{"id":"18510","type":"Disease","text":["anemia"],"offsets":[[742,748]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]},{"id":"18511","type":"Disease","text":["nausea"],"offsets":[[750,756]],"normalized":[{"db_name":"MESH","db_id":"D009325"}]},{"id":"18512","type":"Disease","text":["alopecia"],"offsets":[[763,771]],"normalized":[{"db_name":"MESH","db_id":"D000505"}]},{"id":"18513","type":"Disease","text":["phlebitis"],"offsets":[[773,782]],"normalized":[{"db_name":"MESH","db_id":"D010689"}]},{"id":"18514","type":"Disease","text":["mucositis"],"offsets":[[788,797]],"normalized":[{"db_name":"MESH","db_id":"D052016"}]},{"id":"18515","type":"Disease","text":["Myelosuppression"],"offsets":[[799,815]],"normalized":[{"db_name":"MESH","db_id":"D001855"}]},{"id":"18516","type":"Disease","text":["hepatic dysfunction"],"offsets":[[842,861]],"normalized":[{"db_name":"MESH","db_id":"D008107"}]},{"id":"18517","type":"Chemical","text":["Pirarubicin"],"offsets":[[912,923]],"normalized":[{"db_name":"MESH","db_id":"C027260"}]},{"id":"18518","type":"Chemical","text":["Adriamycinol"],"offsets":[[1207,1219]],"normalized":[{"db_name":"MESH","db_id":"C010013"}]},{"id":"18519","type":"Chemical","text":["doxorubicin"],"offsets":[[1221,1232]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"18520","type":"Chemical","text":["adriamycinone"],"offsets":[[1234,1247]],"normalized":[{"db_name":"MESH","db_id":"C010012"}]},{"id":"18521","type":"Chemical","text":["tetrahydropyranyladriamycinol"],"offsets":[[1253,1282]],"normalized":[{"db_name":"MESH","db_id":"C027260"}]},{"id":"18522","type":"Chemical","text":["doxorubicin"],"offsets":[[1341,1352]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"18523","type":"Chemical","text":["Pirarubicin"],"offsets":[[1430,1441]],"normalized":[{"db_name":"MESH","db_id":"C027260"}]},{"id":"18524","type":"Disease","text":["mesothelioma"],"offsets":[[1517,1529]],"normalized":[{"db_name":"MESH","db_id":"D008654"}]},{"id":"18525","type":"Disease","text":["leiomyosarcoma"],"offsets":[[1531,1545]],"normalized":[{"db_name":"MESH","db_id":"D007890"}]},{"id":"18526","type":"Disease","text":["basal cell carcinoma"],"offsets":[[1551,1571]],"normalized":[{"db_name":"MESH","db_id":"D002280"}]}],"events":[],"coreferences":[],"relations":[{"id":"18527","type":"CID","arg1_id":"18519","arg2_id":"18513","normalized":[]},{"id":"18528","type":"CID","arg1_id":"18522","arg2_id":"18513","normalized":[]},{"id":"18529","type":"CID","arg1_id":"18519","arg2_id":"18508","normalized":[]},{"id":"18530","type":"CID","arg1_id":"18522","arg2_id":"18508","normalized":[]},{"id":"18531","type":"CID","arg1_id":"18519","arg2_id":"18514","normalized":[]},{"id":"18532","type":"CID","arg1_id":"18522","arg2_id":"18514","normalized":[]},{"id":"18533","type":"CID","arg1_id":"18519","arg2_id":"18512","normalized":[]},{"id":"18534","type":"CID","arg1_id":"18522","arg2_id":"18512","normalized":[]},{"id":"18535","type":"CID","arg1_id":"18519","arg2_id":"18509","normalized":[]},{"id":"18536","type":"CID","arg1_id":"18522","arg2_id":"18509","normalized":[]},{"id":"18537","type":"CID","arg1_id":"18519","arg2_id":"18510","normalized":[]},{"id":"18538","type":"CID","arg1_id":"18522","arg2_id":"18510","normalized":[]},{"id":"18539","type":"CID","arg1_id":"18519","arg2_id":"18511","normalized":[]},{"id":"18540","type":"CID","arg1_id":"18522","arg2_id":"18511","normalized":[]}]}
{"id":"18541","document_id":"2440413","passages":[{"id":"18542","type":"title","text":["Differential effects of gamma-hexachlorocyclohexane (lindane) on pharmacologically-induced seizures."],"offsets":[[0,100]]},{"id":"18543","type":"abstract","text":["Gamma-hexachlorocyclohexane (gamma-HCH), the active ingredient of the insecticide lindane, has been shown to decrease seizure threshold to pentylenetrazol (PTZ) 3 h after exposure to gamma-HCH and conversely increase threshold to PTZ-induced seizures 24 h after exposure to gamma-HCH (Vohland et al. 1981). In this study, the severity of response to other seizure-inducing agents was tested in mice 1 and 24 h after intraperitoneal administration of 80 mg\/kg gamma-HCH. One hour after the administration of gamma-HCH, the activity of seizure-inducing agents was increased, regardless of their mechanism, while 24 h after gamma-HCH a differential response was observed. Seizure activity due to PTZ and picrotoxin (PTX) was significantly decreased; however, seizure activity due to 3-mercaptopropionic acid (MPA), bicuculline (BCC), methyl 6,7-dimethoxy-4-ethyl-B-carboline-3-carboxylate (DMCM), or strychnine (STR) was not different from control. In vitro, gamma-HCH, pentylenetetrazol and picrotoxin were shown to inhibit 3H-TBOB binding in mouse whole brain, with IC50 values of 4.6, 404 and 9.4 microM, respectively. MPA, BCC, DMCM, and STR showed no inhibition of 3H-TBOB (t-butyl bicyclo-orthobenzoate) binding at concentrations of 100 micron. The pharmacological challenge data suggest that tolerance may occur to seizure activity induced by PTZ and PTX 24 h after gamma-HCH, since the response to only these two seizure-inducing agents is decreased. The in vitro data suggest that the site responsible for the decrease in seizure activity 24 h after gamma-HCH may be the GABA-A receptor-linked chloride channel."],"offsets":[[101,1718]]}],"entities":[{"id":"18544","type":"Chemical","text":["gamma-hexachlorocyclohexane"],"offsets":[[24,51]],"normalized":[{"db_name":"MESH","db_id":"D001556"}]},{"id":"18545","type":"Chemical","text":["lindane"],"offsets":[[53,60]],"normalized":[{"db_name":"MESH","db_id":"D001556"}]},{"id":"18546","type":"Disease","text":["seizures"],"offsets":[[91,99]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"18547","type":"Chemical","text":["Gamma-hexachlorocyclohexane"],"offsets":[[101,128]],"normalized":[{"db_name":"MESH","db_id":"D001556"}]},{"id":"18548","type":"Chemical","text":["gamma-HCH"],"offsets":[[130,139]],"normalized":[{"db_name":"MESH","db_id":"D001556"}]},{"id":"18549","type":"Chemical","text":["lindane"],"offsets":[[183,190]],"normalized":[{"db_name":"MESH","db_id":"D001556"}]},{"id":"18550","type":"Disease","text":["seizure"],"offsets":[[219,226]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"18551","type":"Chemical","text":["PTZ"],"offsets":[[257,260]],"normalized":[{"db_name":"MESH","db_id":"D010433"}]},{"id":"18552","type":"Chemical","text":["gamma-HCH"],"offsets":[[284,293]],"normalized":[{"db_name":"MESH","db_id":"D001556"}]},{"id":"18553","type":"Chemical","text":["PTZ"],"offsets":[[331,334]],"normalized":[{"db_name":"MESH","db_id":"D010433"}]},{"id":"18554","type":"Disease","text":["seizures"],"offsets":[[343,351]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"18555","type":"Chemical","text":["gamma-HCH"],"offsets":[[375,384]],"normalized":[{"db_name":"MESH","db_id":"D001556"}]},{"id":"18556","type":"Disease","text":["seizure"],"offsets":[[457,464]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"18557","type":"Chemical","text":["gamma-HCH"],"offsets":[[560,569]],"normalized":[{"db_name":"MESH","db_id":"D001556"}]},{"id":"18558","type":"Chemical","text":["gamma-HCH"],"offsets":[[608,617]],"normalized":[{"db_name":"MESH","db_id":"D001556"}]},{"id":"18559","type":"Disease","text":["seizure"],"offsets":[[635,642]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"18560","type":"Chemical","text":["gamma-HCH"],"offsets":[[722,731]],"normalized":[{"db_name":"MESH","db_id":"D001556"}]},{"id":"18561","type":"Disease","text":["Seizure"],"offsets":[[770,777]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"18562","type":"Chemical","text":["PTZ"],"offsets":[[794,797]],"normalized":[{"db_name":"MESH","db_id":"D010433"}]},{"id":"18563","type":"Chemical","text":["picrotoxin"],"offsets":[[802,812]],"normalized":[{"db_name":"MESH","db_id":"D010852"}]},{"id":"18564","type":"Chemical","text":["PTX"],"offsets":[[814,817]],"normalized":[{"db_name":"MESH","db_id":"D010852"}]},{"id":"18565","type":"Disease","text":["seizure"],"offsets":[[857,864]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"18566","type":"Chemical","text":["3-mercaptopropionic 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{"id":"18802","document_id":"12483326","passages":[{"id":"18803","type":"title","text":["Severe ocular and orbital toxicity after intracarotid injection of carboplatin for recurrent glioblastomas."],"offsets":[[0,107]]},{"id":"18804","type":"abstract","text":["BACKGROUND: Glioblastoma is a malignant tumor that occurs in the cerebrum during adulthood. With current treatment regimens including combined surgery, radiation and chemotherapy, the average life expectancy of the patients is limited to approximately 1 year. Therefore, patients with glioblastoma sometimes have intracarotid injection of carcinostatics added to the treatment regimen. Generally, carboplatin is said to have milder side effects than cisplatin, whose ocular and orbital toxicity are well known. However, we experienced a case of severe ocular and orbital toxicity after intracarotid injection of carboplatin, which is infrequently reported. CASE: A 58-year-old man received an intracarotid injection of carboplatin for recurrent glioblastomas in his left temporal lobe. He complained of pain and visual disturbance in the ipsilateral eye 30 h after the injection. Various ocular symptoms and findings caused by carboplatin toxicity were seen. RESULTS: He was treated with intravenous administration of corticosteroids and glycerin for 6 days after the injection. Although the intraocular pressure elevation caused by secondary acute angle-closure glaucoma decreased and ocular pain diminished, inexorable papilledema and exudative retinal detachment continued for 3 weeks. Finally, 6 weeks later, diffuse chorioretinal atrophy with optic atrophy occurred and the vision in his left eye was lost. CONCLUSION: When performing intracarotid injection of carboplatin, we must be aware of its potentially blinding ocular toxicity. It is recommended that further studies and investigations are undertaken in the effort to minimize such severe side effects."],"offsets":[[108,1773]]}],"entities":[{"id":"18805","type":"Disease","text":["ocular and orbital toxicity"],"offsets":[[7,34]],"normalized":[{"db_name":"MESH","db_id":"D005128"},{"db_name":"MESH","db_id":"D009916"}]},{"id":"18806","type":"Disease","text":["ocular","toxicity"],"offsets":[[7,13],[26,34]],"normalized":[{"db_name":"MESH","db_id":"D005128"}]},{"id":"18807","type":"Disease","text":["orbital 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{"id":"18922","document_id":"1664218","passages":[{"id":"18923","type":"title","text":["Phase II study of the amsacrine analogue CI-921 (NSC 343499) in non-small cell lung cancer."],"offsets":[[0,91]]},{"id":"18924","type":"abstract","text":["CI-921 (NSC 343499; 9-[[2-methoxy-4-[(methylsulphonyl)amino]phenyl]amino] -N,5-dimethyl- 4-acridinecarboxamide) is a topoisomerase II poison with high experimental antitumour activity. It was administered by 15 min infusion to 16 evaluable patients with non-small cell lung cancer (NSCLC) (7 with no prior treatment, 9 patients in relapse following surgery\/radiotherapy) at a dose (648 mg\/m2 divided over 3 days, repeated every 3 weeks) determined by phase I trial. Patients had a median performance status of 1 (WHO), and median age of 61 years. The histology comprised squamous carcinoma (11), adenocarcinoma (1), mixed histology (2), bronchio-alveolar carcinoma (1) and large cell undifferentiated carcinoma (1). Neutropenia grade greater than or equal to 3 was seen in 15 patients, infections with recovery in 3, and grand mal seizures in 1 patient. Grade less than or equal to 2 nausea and vomiting occurred in 66% courses and phlebitis in the infusion arm in 37%. 1 patient with squamous cell carcinoma achieved a partial response lasting 5 months. Further testing in this and other tumour types using multiple daily schedules is warranted."],"offsets":[[92,1238]]}],"entities":[{"id":"18925","type":"Chemical","text":["amsacrine"],"offsets":[[22,31]],"normalized":[{"db_name":"MESH","db_id":"D000677"}]},{"id":"18926","type":"Chemical","text":["CI-921"],"offsets":[[41,47]],"normalized":[{"db_name":"MESH","db_id":"C042315"}]},{"id":"18927","type":"Chemical","text":["NSC 343499"],"offsets":[[49,59]],"normalized":[{"db_name":"MESH","db_id":"C042315"}]},{"id":"18928","type":"Disease","text":["non-small cell lung cancer"],"offsets":[[64,90]],"normalized":[{"db_name":"MESH","db_id":"D002289"}]},{"id":"18929","type":"Chemical","text":["CI-921"],"offsets":[[92,98]],"normalized":[{"db_name":"MESH","db_id":"C042315"}]},{"id":"18930","type":"Chemical","text":["NSC 343499"],"offsets":[[100,110]],"normalized":[{"db_name":"MESH","db_id":"C042315"}]},{"id":"18931","type":"Chemical","text":["9-[[2-methoxy-4-[(methylsulphonyl)amino]phenyl]amino] -N,5-dimethyl- 4-acridinecarboxamide"],"offsets":[[112,202]],"normalized":[{"db_name":"MESH","db_id":"C042315"}]},{"id":"18932","type":"Disease","text":["non-small cell lung cancer"],"offsets":[[346,372]],"normalized":[{"db_name":"MESH","db_id":"D002289"}]},{"id":"18933","type":"Disease","text":["NSCLC"],"offsets":[[374,379]],"normalized":[{"db_name":"MESH","db_id":"D002289"}]},{"id":"18934","type":"Disease","text":["squamous carcinoma"],"offsets":[[663,681]],"normalized":[{"db_name":"MESH","db_id":"D002294"}]},{"id":"18935","type":"Disease","text":["adenocarcinoma"],"offsets":[[688,702]],"normalized":[{"db_name":"MESH","db_id":"D000230"}]},{"id":"18936","type":"Disease","text":["bronchio-alveolar carcinoma"],"offsets":[[729,756]],"normalized":[{"db_name":"MESH","db_id":"D002282"}]},{"id":"18937","type":"Disease","text":["undifferentiated 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{"id":"18976","document_id":"18809400","passages":[{"id":"18977","type":"title","text":["Alpha-lipoic acid prevents mitochondrial damage and neurotoxicity in experimental chemotherapy neuropathy."],"offsets":[[0,106]]},{"id":"18978","type":"abstract","text":["The study investigates if alpha-lipoic acid is neuroprotective against chemotherapy induced neurotoxicity, if mitochondrial damage plays a critical role in toxic neurodegenerative cascade, and if neuroprotective effects of alpha-lipoic acid depend on mitochondria protection. We used an in vitro model of chemotherapy induced peripheral neuropathy that closely mimic the in vivo condition by exposing primary cultures of dorsal root ganglion (DRG) sensory neurons to paclitaxel and cisplatin, two widely used and highly effective chemotherapeutic drugs. This approach allowed investigating the efficacy of alpha-lipoic acid in preventing axonal damage and apoptosis and the function and ultrastructural morphology of mitochondria after exposure to toxic agents and alpha-lipoic acid. Our results demonstrate that both cisplatin and paclitaxel cause early mitochondrial impairment with loss of membrane potential and induction of autophagic vacuoles in neurons. Alpha-lipoic acid exerts neuroprotective effects against chemotherapy induced neurotoxicity in sensory neurons: it rescues the mitochondrial toxicity and induces the expression of frataxin, an essential mitochondrial protein with anti-oxidant and chaperone properties. In conclusion mitochondrial toxicity is an early common event both in paclitaxel and cisplatin induced neurotoxicity. Alpha-lipoic acid protects sensory neurons through its anti-oxidant and mitochondrial regulatory functions, possibly inducing the expression of frataxin. These findings suggest that alpha-lipoic acid might reduce the risk of developing peripheral nerve toxicity in patients undergoing chemotherapy and encourage further confirmatory clinical trials."],"offsets":[[107,1804]]}],"entities":[{"id":"18979","type":"Chemical","text":["Alpha-lipoic acid"],"offsets":[[0,17]],"normalized":[{"db_name":"MESH","db_id":"D008063"}]},{"id":"18980","type":"Disease","text":["mitochondrial damage"],"offsets":[[27,47]],"normalized":[{"db_name":"MESH","db_id":"D028361"}]},{"id":"18981","type":"Disease","text":["neurotoxicity"],"offsets":[[52,65]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"18982","type":"Disease","text":["neuropathy"],"offsets":[[95,105]],"normalized":[{"db_name":"MESH","db_id":"D009422"}]},{"id":"18983","type":"Chemical","text":["alpha-lipoic 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neuropathy"],"offsets":[[433,454]],"normalized":[{"db_name":"MESH","db_id":"D010523"}]},{"id":"18989","type":"Chemical","text":["paclitaxel"],"offsets":[[574,584]],"normalized":[{"db_name":"MESH","db_id":"D017239"}]},{"id":"18990","type":"Chemical","text":["cisplatin"],"offsets":[[589,598]],"normalized":[{"db_name":"MESH","db_id":"D002945"}]},{"id":"18991","type":"Chemical","text":["alpha-lipoic acid"],"offsets":[[713,730]],"normalized":[{"db_name":"MESH","db_id":"D008063"}]},{"id":"18992","type":"Disease","text":["axonal damage"],"offsets":[[745,758]],"normalized":[{"db_name":"MESH","db_id":"D001480"}]},{"id":"18993","type":"Chemical","text":["alpha-lipoic 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{"id":"19025","document_id":"17020434","passages":[{"id":"19026","type":"title","text":["Optimising stroke prevention in non-valvular atrial fibrillation."],"offsets":[[0,65]]},{"id":"19027","type":"abstract","text":["Atrial fibrillation is associated with substantial morbidity and mortality. Pooled data from trials comparing antithrombotic treatment with placebo have shown that warfarin reduces the risk of stroke by 62%, and that aspirin alone reduces the risk by 22%. Overall, in high-risk patients, warfarin is superior to aspirin in preventing strokes, with a relative risk reduction of 36%. Ximelagatran, an oral direct thrombin inhibitor, was found to be as efficient as vitamin K antagonist drugs in the prevention of embolic events, but has been recently withdrawn because of abnormal liver function tests. The ACTIVE-W (Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events) study has demonstrated that warfarin is superior to platelet therapy (clopidogrel plus aspirin) in the prevention af embolic events. Idraparinux, a Factor Xa inhibitor, is being evaluated in patients with atrial fibrillation. Angiotensin-converting enzyme inhibitors and angiotensin II receptor-blocking drugs hold promise in atrial fibrillation through cardiac remodelling. Preliminary studies suggest that statins could interfere with the risk of recurrence after electrical cardioversion. Finally, percutaneous methods for the exclusion of left atrial appendage are under investigation in high-risk patients."],"offsets":[[66,1381]]}],"entities":[{"id":"19028","type":"Disease","text":["stroke"],"offsets":[[11,17]],"normalized":[{"db_name":"MESH","db_id":"D020521"}]},{"id":"19029","type":"Disease","text":["atrial fibrillation"],"offsets":[[45,64]],"normalized":[{"db_name":"MESH","db_id":"D001281"}]},{"id":"19030","type":"Disease","text":["Atrial fibrillation"],"offsets":[[66,85]],"normalized":[{"db_name":"MESH","db_id":"D001281"}]},{"id":"19031","type":"Chemical","text":["warfarin"],"offsets":[[230,238]],"normalized":[{"db_name":"MESH","db_id":"D014859"}]},{"id":"19032","type":"Disease","text":["stroke"],"offsets":[[259,265]],"normalized":[{"db_name":"MESH","db_id":"D020521"}]},{"id":"19033","type":"Chemical","text":["aspirin"],"offsets":[[283,290]],"normalized":[{"db_name":"MESH","db_id":"D001241"}]},{"id":"19034","type":"Chemical","text":["warfarin"],"offsets":[[354,362]],"normalized":[{"db_name":"MESH","db_id":"D014859"}]},{"id":"19035","type":"Chemical","text":["aspirin"],"offsets":[[378,385]],"normalized":[{"db_name":"MESH","db_id":"D001241"}]},{"id":"19036","type":"Disease","text":["strokes"],"offsets":[[400,407]],"normalized":[{"db_name":"MESH","db_id":"D020521"}]},{"id":"19037","type":"Chemical","text":["Ximelagatran"],"offsets":[[448,460]],"normalized":[{"db_name":"MESH","db_id":"C426686"}]},{"id":"19038","type":"Chemical","text":["vitamin K"],"offsets":[[529,538]],"normalized":[{"db_name":"MESH","db_id":"D014812"}]},{"id":"19039","type":"Disease","text":["embolic events"],"offsets":[[577,591]],"normalized":[{"db_name":"MESH","db_id":"D004617"}]},{"id":"19040","type":"Disease","text":["abnormal liver function"],"offsets":[[636,659]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"19041","type":"Disease","text":["Atrial Fibrillation"],"offsets":[[681,700]],"normalized":[{"db_name":"MESH","db_id":"D001281"}]},{"id":"19042","type":"Chemical","text":["Clopidogrel"],"offsets":[[701,712]],"normalized":[{"db_name":"MESH","db_id":"C055162"}]},{"id":"19043","type":"Chemical","text":["Irbesartan"],"offsets":[[724,734]],"normalized":[{"db_name":"MESH","db_id":"C081309"}]},{"id":"19044","type":"Chemical","text":["warfarin"],"offsets":[[798,806]],"normalized":[{"db_name":"MESH","db_id":"D014859"}]},{"id":"19045","type":"Chemical","text":["clopidogrel"],"offsets":[[840,851]],"normalized":[{"db_name":"MESH","db_id":"C055162"}]},{"id":"19046","type":"Chemical","text":["aspirin"],"offsets":[[857,864]],"normalized":[{"db_name":"MESH","db_id":"D001241"}]},{"id":"19047","type":"Disease","text":["embolic events"],"offsets":[[887,901]],"normalized":[{"db_name":"MESH","db_id":"D004617"}]},{"id":"19048","type":"Chemical","text":["Idraparinux"],"offsets":[[903,914]],"normalized":[{"db_name":"MESH","db_id":"C479958"}]},{"id":"19049","type":"Disease","text":["atrial fibrillation"],"offsets":[[975,994]],"normalized":[{"db_name":"MESH","db_id":"D001281"}]},{"id":"19050","type":"Chemical","text":["Angiotensin"],"offsets":[[996,1007]],"normalized":[{"db_name":"MESH","db_id":"D000809"}]},{"id":"19051","type":"Chemical","text":["angiotensin II"],"offsets":[[1041,1055]],"normalized":[{"db_name":"MESH","db_id":"D000804"}]},{"id":"19052","type":"Disease","text":["atrial fibrillation"],"offsets":[[1096,1115]],"normalized":[{"db_name":"MESH","db_id":"D001281"}]},{"id":"19053","type":"Disease","text":["cardiac remodelling"],"offsets":[[1124,1143]],"normalized":[{"db_name":"MESH","db_id":"D020257"}]},{"id":"19054","type":"Chemical","text":["statins"],"offsets":[[1178,1185]],"normalized":[{"db_name":"MESH","db_id":"D019821"}]}],"events":[],"coreferences":[],"relations":[{"id":"19055","type":"CID","arg1_id":"19037","arg2_id":"19040","normalized":[]}]}
{"id":"19056","document_id":"3865016","passages":[{"id":"19057","type":"title","text":["Interaction of cyclosporin A with antineoplastic agents."],"offsets":[[0,56]]},{"id":"19058","type":"abstract","text":["A synergistic effect of etoposide and cyclosporin A was observed in a patient with acute T-lymphocytic leukemia in relapse. The concomitant administration of etoposide and cyclosporin A resulted in eradication of hitherto refractory leukemic infiltration of bone marrow. Severe side effects in terms of mental confusion and progressive hyperbilirubinemia, however, point to an enhancement not only of antineoplastic effects but also of toxicity in normal tissues. This report demonstrates for the first time that the pharmacodynamic properties of cyclosporin A may not be confined strictly to suppression of normal T-cell functions."],"offsets":[[57,689]]}],"entities":[{"id":"19059","type":"Chemical","text":["cyclosporin A"],"offsets":[[15,28]],"normalized":[{"db_name":"MESH","db_id":"D016572"}]},{"id":"19060","type":"Chemical","text":["etoposide"],"offsets":[[81,90]],"normalized":[{"db_name":"MESH","db_id":"D005047"}]},{"id":"19061","type":"Chemical","text":["cyclosporin A"],"offsets":[[95,108]],"normalized":[{"db_name":"MESH","db_id":"D016572"}]},{"id":"19062","type":"Disease","text":["acute T-lymphocytic leukemia"],"offsets":[[140,168]],"normalized":[{"db_name":"MESH","db_id":"D054218"}]},{"id":"19063","type":"Chemical","text":["etoposide"],"offsets":[[215,224]],"normalized":[{"db_name":"MESH","db_id":"D005047"}]},{"id":"19064","type":"Chemical","text":["cyclosporin A"],"offsets":[[229,242]],"normalized":[{"db_name":"MESH","db_id":"D016572"}]},{"id":"19065","type":"Disease","text":["leukemic infiltration"],"offsets":[[290,311]],"normalized":[{"db_name":"MESH","db_id":"D017254"}]},{"id":"19066","type":"Disease","text":["confusion"],"offsets":[[367,376]],"normalized":[{"db_name":"MESH","db_id":"D003221"}]},{"id":"19067","type":"Disease","text":["hyperbilirubinemia"],"offsets":[[393,411]],"normalized":[{"db_name":"MESH","db_id":"D006932"}]},{"id":"19068","type":"Disease","text":["toxicity"],"offsets":[[493,501]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"19069","type":"Chemical","text":["cyclosporin A"],"offsets":[[604,617]],"normalized":[{"db_name":"MESH","db_id":"D016572"}]}],"events":[],"coreferences":[],"relations":[{"id":"19070","type":"CID","arg1_id":"19059","arg2_id":"19066","normalized":[]},{"id":"19071","type":"CID","arg1_id":"19061","arg2_id":"19066","normalized":[]},{"id":"19072","type":"CID","arg1_id":"19064","arg2_id":"19066","normalized":[]},{"id":"19073","type":"CID","arg1_id":"19069","arg2_id":"19066","normalized":[]},{"id":"19074","type":"CID","arg1_id":"19060","arg2_id":"19067","normalized":[]},{"id":"19075","type":"CID","arg1_id":"19063","arg2_id":"19067","normalized":[]},{"id":"19076","type":"CID","arg1_id":"19060","arg2_id":"19066","normalized":[]},{"id":"19077","type":"CID","arg1_id":"19063","arg2_id":"19066","normalized":[]},{"id":"19078","type":"CID","arg1_id":"19059","arg2_id":"19067","normalized":[]},{"id":"19079","type":"CID","arg1_id":"19061","arg2_id":"19067","normalized":[]},{"id":"19080","type":"CID","arg1_id":"19064","arg2_id":"19067","normalized":[]},{"id":"19081","type":"CID","arg1_id":"19069","arg2_id":"19067","normalized":[]}]}
{"id":"19082","document_id":"3629586","passages":[{"id":"19083","type":"title","text":["The hematologic effects of cefonicid and cefazedone in the dog: a potential model of cephalosporin hematotoxicity in man."],"offsets":[[0,121]]},{"id":"19084","type":"abstract","text":["Cephalosporin antibiotics cause a variety of hematologic disturbances in man, the pathogeneses and hematopathology of which remain poorly characterized. There is a need for a well-defined animal model in which these blood dyscrasias can be studied. In four subacute toxicity studies, the intravenous administration of cefonicid or cefazedone to beagle dogs caused a dose-dependent incidence of anemia, neutropenia, and thrombocytopenia after 1-3 months of treatment. A nonregenerative anemia was the most compromising of the cytopenias and occurred in approximately 50% of dogs receiving 400-500 mg\/kg cefonicid or 540-840 mg\/kg cefazedone. All three cytopenias were completely reversible following cessation of treatment; the time required for recovery of the erythron (approximately 1 month) was considerably longer than that of the granulocytes and platelets (hours to a few days). Upon rechallenge with either cephalosporin, the hematologic syndrome was reproduced in most dogs tested; cefonicid (but not cefazedone)-treated dogs showed a substantially reduced induction period (15 +\/- 5 days) compared to that of the first exposure to the drug (61 +\/- 24 days). This observation, along with the rapid rate of decline in red cell mass parameters of affected dogs, suggests that a hemolytic component complicated the red cell production problem and that multiple toxicologic mechanisms contributed to the cytopenia. We conclude that the administration of high doses of cefonicid or cefazedone to dogs can induce hematotoxicity similar to the cephalosporin-induced blood dyscrasias described in man and thus provides a useful model for studying the mechanisms of these disorders."],"offsets":[[122,1803]]}],"entities":[{"id":"19085","type":"Chemical","text":["cefonicid"],"offsets":[[27,36]],"normalized":[{"db_name":"MESH","db_id":"D015790"}]},{"id":"19086","type":"Chemical","text":["cefazedone"],"offsets":[[41,51]],"normalized":[{"db_name":"MESH","db_id":"C021341"}]},{"id":"19087","type":"Chemical","text":["cephalosporin"],"offsets":[[85,98]],"normalized":[{"db_name":"MESH","db_id":"D002511"}]},{"id":"19088","type":"Disease","text":["hematotoxicity"],"offsets":[[99,113]],"normalized":[{"db_name":"MESH","db_id":"D006402"}]},{"id":"19089","type":"Chemical","text":["Cephalosporin"],"offsets":[[122,135]],"normalized":[{"db_name":"MESH","db_id":"D002511"}]},{"id":"19090","type":"Disease","text":["hematologic disturbances"],"offsets":[[167,191]],"normalized":[{"db_name":"MESH","db_id":"D006402"}]},{"id":"19091","type":"Disease","text":["blood dyscrasias"],"offsets":[[338,354]],"normalized":[{"db_name":"MESH","db_id":"D006402"}]},{"id":"19092","type":"Disease","text":["toxicity"],"offsets":[[388,396]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"19093","type":"Chemical","text":["cefonicid"],"offsets":[[440,449]],"normalized":[{"db_name":"MESH","db_id":"D015790"}]},{"id":"19094","type":"Chemical","text":["cefazedone"],"offsets":[[453,463]],"normalized":[{"db_name":"MESH","db_id":"C021341"}]},{"id":"19095","type":"Disease","text":["anemia"],"offsets":[[516,522]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]},{"id":"19096","type":"Disease","text":["neutropenia"],"offsets":[[524,535]],"normalized":[{"db_name":"MESH","db_id":"D009503"}]},{"id":"19097","type":"Disease","text":["thrombocytopenia"],"offsets":[[541,557]],"normalized":[{"db_name":"MESH","db_id":"D013921"}]},{"id":"19098","type":"Disease","text":["anemia"],"offsets":[[607,613]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]},{"id":"19099","type":"Disease","text":["cytopenias"],"offsets":[[647,657]],"normalized":[{"db_name":"MESH","db_id":"D006402"}]},{"id":"19100","type":"Chemical","text":["cefonicid"],"offsets":[[724,733]],"normalized":[{"db_name":"MESH","db_id":"D015790"}]},{"id":"19101","type":"Chemical","text":["cefazedone"],"offsets":[[751,761]],"normalized":[{"db_name":"MESH","db_id":"C021341"}]},{"id":"19102","type":"Disease","text":["cytopenias"],"offsets":[[773,783]],"normalized":[{"db_name":"MESH","db_id":"D006402"}]},{"id":"19103","type":"Chemical","text":["cephalosporin"],"offsets":[[1036,1049]],"normalized":[{"db_name":"MESH","db_id":"D002511"}]},{"id":"19104","type":"Disease","text":["hematologic syndrome"],"offsets":[[1055,1075]],"normalized":[{"db_name":"MESH","db_id":"D006402"}]},{"id":"19105","type":"Chemical","text":["cefonicid"],"offsets":[[1112,1121]],"normalized":[{"db_name":"MESH","db_id":"D015790"}]},{"id":"19106","type":"Chemical","text":["cefazedone"],"offsets":[[1131,1141]],"normalized":[{"db_name":"MESH","db_id":"C021341"}]},{"id":"19107","type":"Disease","text":["hemolytic"],"offsets":[[1406,1415]],"normalized":[{"db_name":"MESH","db_id":"D006461"}]},{"id":"19108","type":"Disease","text":["cytopenia"],"offsets":[[1530,1539]],"normalized":[{"db_name":"MESH","db_id":"D006402"}]},{"id":"19109","type":"Chemical","text":["cefonicid"],"offsets":[[1594,1603]],"normalized":[{"db_name":"MESH","db_id":"D015790"}]},{"id":"19110","type":"Chemical","text":["cefazedone"],"offsets":[[1607,1617]],"normalized":[{"db_name":"MESH","db_id":"C021341"}]},{"id":"19111","type":"Disease","text":["hematotoxicity"],"offsets":[[1637,1651]],"normalized":[{"db_name":"MESH","db_id":"D006402"}]},{"id":"19112","type":"Chemical","text":["cephalosporin"],"offsets":[[1667,1680]],"normalized":[{"db_name":"MESH","db_id":"D002511"}]},{"id":"19113","type":"Disease","text":["blood dyscrasias"],"offsets":[[1689,1705]],"normalized":[{"db_name":"MESH","db_id":"D006402"}]}],"events":[],"coreferences":[],"relations":[{"id":"19114","type":"CID","arg1_id":"19086","arg2_id":"19096","normalized":[]},{"id":"19115","type":"CID","arg1_id":"19094","arg2_id":"19096","normalized":[]},{"id":"19116","type":"CID","arg1_id":"19101","arg2_id":"19096","normalized":[]},{"id":"19117","type":"CID","arg1_id":"19106","arg2_id":"19096","normalized":[]},{"id":"19118","type":"CID","arg1_id":"19110","arg2_id":"19096","normalized":[]},{"id":"19119","type":"CID","arg1_id":"19085","arg2_id":"19097","normalized":[]},{"id":"19120","type":"CID","arg1_id":"19093","arg2_id":"19097","normalized":[]},{"id":"19121","type":"CID","arg1_id":"19100","arg2_id":"19097","normalized":[]},{"id":"19122","type":"CID","arg1_id":"19105","arg2_id":"19097","normalized":[]},{"id":"19123","type":"CID","arg1_id":"19109","arg2_id":"19097","normalized":[]},{"id":"19124","type":"CID","arg1_id":"19085","arg2_id":"19095","normalized":[]},{"id":"19125","type":"CID","arg1_id":"19085","arg2_id":"19098","normalized":[]},{"id":"19126","type":"CID","arg1_id":"19093","arg2_id":"19095","normalized":[]},{"id":"19127","type":"CID","arg1_id":"19093","arg2_id":"19098","normalized":[]},{"id":"19128","type":"CID","arg1_id":"19100","arg2_id":"19095","normalized":[]},{"id":"19129","type":"CID","arg1_id":"19100","arg2_id":"19098","normalized":[]},{"id":"19130","type":"CID","arg1_id":"19105","arg2_id":"19095","normalized":[]},{"id":"19131","type":"CID","arg1_id":"19105","arg2_id":"19098","normalized":[]},{"id":"19132","type":"CID","arg1_id":"19109","arg2_id":"19095","normalized":[]},{"id":"19133","type":"CID","arg1_id":"19109","arg2_id":"19098","normalized":[]},{"id":"19134","type":"CID","arg1_id":"19086","arg2_id":"19097","normalized":[]},{"id":"19135","type":"CID","arg1_id":"19094","arg2_id":"19097","normalized":[]},{"id":"19136","type":"CID","arg1_id":"19101","arg2_id":"19097","normalized":[]},{"id":"19137","type":"CID","arg1_id":"19106","arg2_id":"19097","normalized":[]},{"id":"19138","type":"CID","arg1_id":"19110","arg2_id":"19097","normalized":[]},{"id":"19139","type":"CID","arg1_id":"19085","arg2_id":"19096","normalized":[]},{"id":"19140","type":"CID","arg1_id":"19093","arg2_id":"19096","normalized":[]},{"id":"19141","type":"CID","arg1_id":"19100","arg2_id":"19096","normalized":[]},{"id":"19142","type":"CID","arg1_id":"19105","arg2_id":"19096","normalized":[]},{"id":"19143","type":"CID","arg1_id":"19109","arg2_id":"19096","normalized":[]},{"id":"19144","type":"CID","arg1_id":"19086","arg2_id":"19095","normalized":[]},{"id":"19145","type":"CID","arg1_id":"19086","arg2_id":"19098","normalized":[]},{"id":"19146","type":"CID","arg1_id":"19094","arg2_id":"19095","normalized":[]},{"id":"19147","type":"CID","arg1_id":"19094","arg2_id":"19098","normalized":[]},{"id":"19148","type":"CID","arg1_id":"19101","arg2_id":"19095","normalized":[]},{"id":"19149","type":"CID","arg1_id":"19101","arg2_id":"19098","normalized":[]},{"id":"19150","type":"CID","arg1_id":"19106","arg2_id":"19095","normalized":[]},{"id":"19151","type":"CID","arg1_id":"19106","arg2_id":"19098","normalized":[]},{"id":"19152","type":"CID","arg1_id":"19110","arg2_id":"19095","normalized":[]},{"id":"19153","type":"CID","arg1_id":"19110","arg2_id":"19098","normalized":[]}]}
{"id":"19154","document_id":"150790","passages":[{"id":"19155","type":"title","text":["A pyridoxine-dependent behavioral disorder unmasked by isoniazid."],"offsets":[[0,65]]},{"id":"19156","type":"abstract","text":["A 3-year-old girl had behavioral deterioration, with hyperkinesis, irritability, and sleeping difficulties after the therapeutic administration of isoniazid. The administration of pharmacologic doses of pyridoxine hydrochloride led to a disappearance of symptoms. After discontinuing isoniazid therapy a similar pattern of behavior was noted that was controlled by pyridoxine. A placebo had no effect, but niacinamide was as effective as pyridoxine. Periodic withdrawal of pyridoxine was associated with return of the hyperkinesis. The level of pyridoxal in the blood was normal during the periods of relapse. Metabolic studies suggested a block in the kynurenine pathway of tryptophan metabolism. The patient has been followed for six years and has required pharmacologic doses of pyridoxine to control her behavior."],"offsets":[[66,883]]}],"entities":[{"id":"19157","type":"Chemical","text":["pyridoxine"],"offsets":[[2,12]],"normalized":[{"db_name":"MESH","db_id":"D011736"}]},{"id":"19158","type":"Disease","text":["behavioral disorder"],"offsets":[[23,42]],"normalized":[{"db_name":"MESH","db_id":"D002653"}]},{"id":"19159","type":"Chemical","text":["isoniazid"],"offsets":[[55,64]],"normalized":[{"db_name":"MESH","db_id":"D007538"}]},{"id":"19160","type":"Disease","text":["behavioral deterioration"],"offsets":[[88,112]],"normalized":[{"db_name":"MESH","db_id":"D002653"}]},{"id":"19161","type":"Disease","text":["hyperkinesis"],"offsets":[[119,131]],"normalized":[{"db_name":"MESH","db_id":"D006948"}]},{"id":"19162","type":"Disease","text":["irritability"],"offsets":[[133,145]],"normalized":[{"db_name":"MESH","db_id":"D001523"}]},{"id":"19163","type":"Disease","text":["sleeping difficulties"],"offsets":[[151,172]],"normalized":[{"db_name":"MESH","db_id":"D012893"}]},{"id":"19164","type":"Chemical","text":["isoniazid"],"offsets":[[213,222]],"normalized":[{"db_name":"MESH","db_id":"D007538"}]},{"id":"19165","type":"Chemical","text":["pyridoxine hydrochloride"],"offsets":[[269,293]],"normalized":[{"db_name":"MESH","db_id":"D011736"}]},{"id":"19166","type":"Chemical","text":["isoniazid"],"offsets":[[350,359]],"normalized":[{"db_name":"MESH","db_id":"D007538"}]},{"id":"19167","type":"Chemical","text":["pyridoxine"],"offsets":[[431,441]],"normalized":[{"db_name":"MESH","db_id":"D011736"}]},{"id":"19168","type":"Chemical","text":["niacinamide"],"offsets":[[472,483]],"normalized":[{"db_name":"MESH","db_id":"D009536"}]},{"id":"19169","type":"Chemical","text":["pyridoxine"],"offsets":[[504,514]],"normalized":[{"db_name":"MESH","db_id":"D011736"}]},{"id":"19170","type":"Chemical","text":["pyridoxine"],"offsets":[[539,549]],"normalized":[{"db_name":"MESH","db_id":"D011736"}]},{"id":"19171","type":"Disease","text":["hyperkinesis"],"offsets":[[584,596]],"normalized":[{"db_name":"MESH","db_id":"D006948"}]},{"id":"19172","type":"Chemical","text":["pyridoxal"],"offsets":[[611,620]],"normalized":[{"db_name":"MESH","db_id":"D011730"}]},{"id":"19173","type":"Chemical","text":["kynurenine"],"offsets":[[719,729]],"normalized":[{"db_name":"MESH","db_id":"D007737"}]},{"id":"19174","type":"Chemical","text":["tryptophan"],"offsets":[[741,751]],"normalized":[{"db_name":"MESH","db_id":"D014364"}]},{"id":"19175","type":"Chemical","text":["pyridoxine"],"offsets":[[848,858]],"normalized":[{"db_name":"MESH","db_id":"D011736"}]}],"events":[],"coreferences":[],"relations":[{"id":"19176","type":"CID","arg1_id":"19159","arg2_id":"19161","normalized":[]},{"id":"19177","type":"CID","arg1_id":"19159","arg2_id":"19171","normalized":[]},{"id":"19178","type":"CID","arg1_id":"19164","arg2_id":"19161","normalized":[]},{"id":"19179","type":"CID","arg1_id":"19164","arg2_id":"19171","normalized":[]},{"id":"19180","type":"CID","arg1_id":"19166","arg2_id":"19161","normalized":[]},{"id":"19181","type":"CID","arg1_id":"19166","arg2_id":"19171","normalized":[]},{"id":"19182","type":"CID","arg1_id":"19159","arg2_id":"19158","normalized":[]},{"id":"19183","type":"CID","arg1_id":"19159","arg2_id":"19160","normalized":[]},{"id":"19184","type":"CID","arg1_id":"19164","arg2_id":"19158","normalized":[]},{"id":"19185","type":"CID","arg1_id":"19164","arg2_id":"19160","normalized":[]},{"id":"19186","type":"CID","arg1_id":"19166","arg2_id":"19158","normalized":[]},{"id":"19187","type":"CID","arg1_id":"19166","arg2_id":"19160","normalized":[]}]}
{"id":"19188","document_id":"10579464","passages":[{"id":"19189","type":"title","text":["A selective dopamine D4 receptor antagonist, NRA0160: a preclinical neuropharmacological profile."],"offsets":[[0,97]]},{"id":"19190","type":"abstract","text":["NRA0160, 5 - [2- ( 4- ( 3 - fluorobenzylidene) piperidin-1-yl) ethyl] - 4 -(4-fluorophenyl) thiazole-2-carboxamide, has a high affinity for human cloned dopamine D4.2, D4.4 and D4.7 receptors, with Ki values of 0.5, 0.9 and 2.7 nM, respectively. NRA0160 is over 20,000fold more potent at the dopamine D4.2 receptor compared with the human cloned dopamine D2L receptor. NRA0160 has negligible affinity for the human cloned dopamine D3 receptor (Ki=39 nM), rat serotonin (5-HT)2A receptors (Ki=180 nM) and rat alpha1 adrenoceptor (Ki=237 nM). NRA0160 and clozapine antagonized locomotor hyperactivity induced by methamphetamine (MAP) in mice. NRA0160 and clozapine antagonized MAP-induced stereotyped behavior in mice, although their effects did not exceed 50% inhibition, even at the highest dose given. NRA0160 and clozapine significantly induced catalepsy in rats, although their effects did not exceed 50% induction even at the highest dose given. NRA0160 and clozapine significantly reversed the disruption of prepulse inhibition (PPI) in rats produced by apomorphine. NRA0160 and clozapine significantly shortened the phencyclidine (PCP)-induced prolonged swimming latency in rats in a water maze task. These findings suggest that NRA0160 may have unique antipsychotic activities without the liability of motor side effects typical of classical antipsychotics."],"offsets":[[98,1462]]}],"entities":[{"id":"19191","type":"Chemical","text":["dopamine"],"offsets":[[12,20]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"19192","type":"Chemical","text":["NRA0160"],"offsets":[[45,52]],"normalized":[{"db_name":"MESH","db_id":"C121249"}]},{"id":"19193","type":"Chemical","text":["NRA0160"],"offsets":[[98,105]],"normalized":[{"db_name":"MESH","db_id":"C121249"}]},{"id":"19194","type":"Chemical","text":["5 - [2- ( 4- ( 3 - fluorobenzylidene) piperidin-1-yl) ethyl] - 4 -(4-fluorophenyl) thiazole-2-carboxamide"],"offsets":[[107,212]],"normalized":[{"db_name":"MESH","db_id":"C121249"}]},{"id":"19195","type":"Chemical","text":["dopamine"],"offsets":[[251,259]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"19196","type":"Chemical","text":["NRA0160"],"offsets":[[344,351]],"normalized":[{"db_name":"MESH","db_id":"C121249"}]},{"id":"19197","type":"Chemical","text":["dopamine"],"offsets":[[390,398]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"19198","type":"Chemical","text":["dopamine"],"offsets":[[444,452]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"19199","type":"Chemical","text":["NRA0160"],"offsets":[[467,474]],"normalized":[{"db_name":"MESH","db_id":"C121249"}]},{"id":"19200","type":"Chemical","text":["dopamine"],"offsets":[[520,528]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"19201","type":"Chemical","text":["serotonin"],"offsets":[[557,566]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"19202","type":"Chemical","text":["5-HT"],"offsets":[[568,572]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"19203","type":"Chemical","text":["NRA0160"],"offsets":[[639,646]],"normalized":[{"db_name":"MESH","db_id":"C121249"}]},{"id":"19204","type":"Chemical","text":["clozapine"],"offsets":[[651,660]],"normalized":[{"db_name":"MESH","db_id":"D003024"}]},{"id":"19205","type":"Disease","text":["hyperactivity"],"offsets":[[683,696]],"normalized":[{"db_name":"MESH","db_id":"D006948"}]},{"id":"19206","type":"Chemical","text":["methamphetamine"],"offsets":[[708,723]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"19207","type":"Chemical","text":["MAP"],"offsets":[[725,728]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"19208","type":"Chemical","text":["NRA0160"],"offsets":[[739,746]],"normalized":[{"db_name":"MESH","db_id":"C121249"}]},{"id":"19209","type":"Chemical","text":["clozapine"],"offsets":[[751,760]],"normalized":[{"db_name":"MESH","db_id":"D003024"}]},{"id":"19210","type":"Chemical","text":["MAP"],"offsets":[[773,776]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"19211","type":"Chemical","text":["NRA0160"],"offsets":[[901,908]],"normalized":[{"db_name":"MESH","db_id":"C121249"}]},{"id":"19212","type":"Chemical","text":["clozapine"],"offsets":[[913,922]],"normalized":[{"db_name":"MESH","db_id":"D003024"}]},{"id":"19213","type":"Disease","text":["catalepsy"],"offsets":[[945,954]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"19214","type":"Chemical","text":["NRA0160"],"offsets":[[1048,1055]],"normalized":[{"db_name":"MESH","db_id":"C121249"}]},{"id":"19215","type":"Chemical","text":["clozapine"],"offsets":[[1060,1069]],"normalized":[{"db_name":"MESH","db_id":"D003024"}]},{"id":"19216","type":"Chemical","text":["apomorphine"],"offsets":[[1157,1168]],"normalized":[{"db_name":"MESH","db_id":"D001058"}]},{"id":"19217","type":"Chemical","text":["NRA0160"],"offsets":[[1170,1177]],"normalized":[{"db_name":"MESH","db_id":"C121249"}]},{"id":"19218","type":"Chemical","text":["clozapine"],"offsets":[[1182,1191]],"normalized":[{"db_name":"MESH","db_id":"D003024"}]},{"id":"19219","type":"Chemical","text":["phencyclidine"],"offsets":[[1220,1233]],"normalized":[{"db_name":"MESH","db_id":"D010622"}]},{"id":"19220","type":"Chemical","text":["PCP"],"offsets":[[1235,1238]],"normalized":[{"db_name":"MESH","db_id":"D010622"}]},{"id":"19221","type":"Chemical","text":["NRA0160"],"offsets":[[1333,1340]],"normalized":[{"db_name":"MESH","db_id":"C121249"}]}],"events":[],"coreferences":[],"relations":[{"id":"19222","type":"CID","arg1_id":"19206","arg2_id":"19205","normalized":[]},{"id":"19223","type":"CID","arg1_id":"19207","arg2_id":"19205","normalized":[]},{"id":"19224","type":"CID","arg1_id":"19210","arg2_id":"19205","normalized":[]},{"id":"19225","type":"CID","arg1_id":"19204","arg2_id":"19213","normalized":[]},{"id":"19226","type":"CID","arg1_id":"19209","arg2_id":"19213","normalized":[]},{"id":"19227","type":"CID","arg1_id":"19212","arg2_id":"19213","normalized":[]},{"id":"19228","type":"CID","arg1_id":"19215","arg2_id":"19213","normalized":[]},{"id":"19229","type":"CID","arg1_id":"19218","arg2_id":"19213","normalized":[]},{"id":"19230","type":"CID","arg1_id":"19192","arg2_id":"19213","normalized":[]},{"id":"19231","type":"CID","arg1_id":"19193","arg2_id":"19213","normalized":[]},{"id":"19232","type":"CID","arg1_id":"19194","arg2_id":"19213","normalized":[]},{"id":"19233","type":"CID","arg1_id":"19196","arg2_id":"19213","normalized":[]},{"id":"19234","type":"CID","arg1_id":"19199","arg2_id":"19213","normalized":[]},{"id":"19235","type":"CID","arg1_id":"19203","arg2_id":"19213","normalized":[]},{"id":"19236","type":"CID","arg1_id":"19208","arg2_id":"19213","normalized":[]},{"id":"19237","type":"CID","arg1_id":"19211","arg2_id":"19213","normalized":[]},{"id":"19238","type":"CID","arg1_id":"19214","arg2_id":"19213","normalized":[]},{"id":"19239","type":"CID","arg1_id":"19217","arg2_id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{"id":"19241","document_id":"3496378","passages":[{"id":"19242","type":"title","text":["Prolonged cholestasis after troleandomycin-induced acute hepatitis."],"offsets":[[0,67]]},{"id":"19243","type":"abstract","text":["We report the case of a patient in whom troleandomycin-induced hepatitis was followed by prolonged anicteric cholestasis. Jaundice occurred after administration of troleandomycin for 7 days and was associated with hypereosinophilia. Jaundice disappeared within 3 months but was followed by prolonged anicteric cholestasis marked by pruritus and high levels of alkaline phosphatase and gammaglutamyltransferase activities. Finally, pruritus disappeared within 19 months, and liver tests returned to normal 27 months after the onset of hepatitis. This observation demonstrates that prolonged cholestasis can follow troleandomycin-induced acute hepatitis."],"offsets":[[68,720]]}],"entities":[{"id":"19244","type":"Disease","text":["cholestasis"],"offsets":[[10,21]],"normalized":[{"db_name":"MESH","db_id":"D002779"}]},{"id":"19245","type":"Chemical","text":["troleandomycin"],"offsets":[[28,42]],"normalized":[{"db_name":"MESH","db_id":"D014217"}]},{"id":"19246","type":"Disease","text":["hepatitis"],"offsets":[[57,66]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"19247","type":"Chemical","text":["troleandomycin"],"offsets":[[108,122]],"normalized":[{"db_name":"MESH","db_id":"D014217"}]},{"id":"19248","type":"Disease","text":["hepatitis"],"offsets":[[131,140]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"19249","type":"Disease","text":["cholestasis"],"offsets":[[177,188]],"normalized":[{"db_name":"MESH","db_id":"D002779"}]},{"id":"19250","type":"Disease","text":["Jaundice"],"offsets":[[190,198]],"normalized":[{"db_name":"MESH","db_id":"D007565"}]},{"id":"19251","type":"Chemical","text":["troleandomycin"],"offsets":[[232,246]],"normalized":[{"db_name":"MESH","db_id":"D014217"}]},{"id":"19252","type":"Disease","text":["hypereosinophilia"],"offsets":[[282,299]],"normalized":[{"db_name":"MESH","db_id":"D004802"}]},{"id":"19253","type":"Disease","text":["Jaundice"],"offsets":[[301,309]],"normalized":[{"db_name":"MESH","db_id":"D007565"}]},{"id":"19254","type":"Disease","text":["cholestasis"],"offsets":[[378,389]],"normalized":[{"db_name":"MESH","db_id":"D002779"}]},{"id":"19255","type":"Disease","text":["pruritus"],"offsets":[[400,408]],"normalized":[{"db_name":"MESH","db_id":"D011537"}]},{"id":"19256","type":"Disease","text":["pruritus"],"offsets":[[499,507]],"normalized":[{"db_name":"MESH","db_id":"D011537"}]},{"id":"19257","type":"Disease","text":["hepatitis"],"offsets":[[602,611]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"19258","type":"Disease","text":["cholestasis"],"offsets":[[658,669]],"normalized":[{"db_name":"MESH","db_id":"D002779"}]},{"id":"19259","type":"Chemical","text":["troleandomycin"],"offsets":[[681,695]],"normalized":[{"db_name":"MESH","db_id":"D014217"}]},{"id":"19260","type":"Disease","text":["hepatitis"],"offsets":[[710,719]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]}],"events":[],"coreferences":[],"relations":[{"id":"19261","type":"CID","arg1_id":"19245","arg2_id":"19244","normalized":[]},{"id":"19262","type":"CID","arg1_id":"19245","arg2_id":"19249","normalized":[]},{"id":"19263","type":"CID","arg1_id":"19245","arg2_id":"19254","normalized":[]},{"id":"19264","type":"CID","arg1_id":"19245","arg2_id":"19258","normalized":[]},{"id":"19265","type":"CID","arg1_id":"19247","arg2_id":"19244","normalized":[]},{"id":"19266","type":"CID","arg1_id":"19247","arg2_id":"19249","normalized":[]},{"id":"19267","type":"CID","arg1_id":"19247","arg2_id":"19254","normalized":[]},{"id":"19268","type":"CID","arg1_id":"19247","arg2_id":"19258","normalized":[]},{"id":"19269","type":"CID","arg1_id":"19251","arg2_id":"19244","normalized":[]},{"id":"19270","type":"CID","arg1_id":"19251","arg2_id":"19249","normalized":[]},{"id":"19271","type":"CID","arg1_id":"19251","arg2_id":"19254","normalized":[]},{"id":"19272","type":"CID","arg1_id":"19251","arg2_id":"19258","normalized":[]},{"id":"19273","type":"CID","arg1_id":"19259","arg2_id":"19244","normalized":[]},{"id":"19274","type":"CID","arg1_id":"19259","arg2_id":"19249","normalized":[]},{"id":"19275","type":"CID","arg1_id":"19259","arg2_id":"19254","normalized":[]},{"id":"19276","type":"CID","arg1_id":"19259","arg2_id":"19258","normalized":[]},{"id":"19277","type":"CID","arg1_id":"19245","arg2_id":"19250","normalized":[]},{"id":"19278","type":"CID","arg1_id":"19245","arg2_id":"19253","normalized":[]},{"id":"19279","type":"CID","arg1_id":"19247","arg2_id":"19250","normalized":[]},{"id":"19280","type":"CID","arg1_id":"19247","arg2_id":"19253","normalized":[]},{"id":"19281","type":"CID","arg1_id":"19251","arg2_id":"19250","normalized":[]},{"id":"19282","type":"CID","arg1_id":"19251","arg2_id":"19253","normalized":[]},{"id":"19283","type":"CID","arg1_id":"19259","arg2_id":"19250","normalized":[]},{"id":"19284","type":"CID","arg1_id":"19259","arg2_id":"19253","normalized":[]},{"id":"19285","type":"CID","arg1_id":"19245","arg2_id":"19252","normalized":[]},{"id":"19286","type":"CID","arg1_id":"19247","arg2_id":"19252","normalized":[]},{"id":"19287","type":"CID","arg1_id":"19251","arg2_id":"19252","normalized":[]},{"id":"19288","type":"CID","arg1_id":"19259","arg2_id":"19252","normalized":[]},{"id":"19289","type":"CID","arg1_id":"19245","arg2_id":"19255","normalized":[]},{"id":"19290","type":"CID","arg1_id":"19245","arg2_id":"19256","normalized":[]},{"id":"19291","type":"CID","arg1_id":"19247","arg2_id":"19255","normalized":[]},{"id":"19292","type":"CID","arg1_id":"19247","arg2_id":"19256","normalized":[]},{"id":"19293","type":"CID","arg1_id":"19251","arg2_id":"19255","normalized":[]},{"id":"19294","type":"CID","arg1_id":"19251","arg2_id":"19256","normalized":[]}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{"id":"19313","document_id":"3076126","passages":[{"id":"19314","type":"title","text":["HMG CoA reductase inhibitors. Current clinical experience."],"offsets":[[0,58]]},{"id":"19315","type":"abstract","text":["Lovastatin and simvastatin are the 2 best-known members of the class of hypolipidaemic agents known as HMG CoA reductase inhibitors. Clinical experience with lovastatin includes over 5000 patients, 700 of whom have been treated for 2 years or more, and experience with simvastatin includes over 3500 patients, of whom 350 have been treated for 18 months or more. Lovastatin has been marketed in the United States for over 6 months. Both agents show substantial clinical efficacy, with reductions in total cholesterol of over 30% and in LDL-cholesterol of 40% in clinical studies. Modest increases in HDL-cholesterol levels of about 10% are also reported. Clinical tolerability of both agents has been good, with fewer than 3% of patients withdrawn from treatment because of clinical adverse experiences. Ophthalmological examinations in over 1100 patients treated with one or the other agent have revealed no evidence of significant short term (up to 2 years) cataractogenic potential. One to 2% of patients have elevations of serum transaminases to greater than 3 times the upper limit of normal. These episodes are asymptomatic and reversible when therapy is discontinued. Minor elevations of creatine kinase levels are reported in about 5% of patients. Myopathy, associated in some cases with myoglobinuria, and in 2 cases with transient renal failure, has been rarely reported with lovastatin, especially in patients concomitantly treated with cyclosporin, gemfibrozil or niacin. Lovastatin and simvastatin are both effective and well-tolerated agents for lowering elevated levels of serum cholesterol. As wider use confirms their safety profile, they will gain increasing importance in the therapeutic approach to hypercholesterolaemia and its consequences."],"offsets":[[59,1821]]}],"entities":[{"id":"19316","type":"Chemical","text":["Lovastatin"],"offsets":[[59,69]],"normalized":[{"db_name":"MESH","db_id":"D008148"}]},{"id":"19317","type":"Chemical","text":["simvastatin"],"offsets":[[74,85]],"normalized":[{"db_name":"MESH","db_id":"D019821"}]},{"id":"19318","type":"Chemical","text":["lovastatin"],"offsets":[[217,227]],"normalized":[{"db_name":"MESH","db_id":"D008148"}]},{"id":"19319","type":"Chemical","text":["simvastatin"],"offsets":[[328,339]],"normalized":[{"db_name":"MESH","db_id":"D019821"}]},{"id":"19320","type":"Chemical","text":["Lovastatin"],"offsets":[[422,432]],"normalized":[{"db_name":"MESH","db_id":"D008148"}]},{"id":"19321","type":"Chemical","text":["cholesterol"],"offsets":[[564,575]],"normalized":[{"db_name":"MESH","db_id":"D002784"}]},{"id":"19322","type":"Chemical","text":["cholesterol"],"offsets":[[599,610]],"normalized":[{"db_name":"MESH","db_id":"D002784"}]},{"id":"19323","type":"Chemical","text":["cholesterol"],"offsets":[[663,674]],"normalized":[{"db_name":"MESH","db_id":"D002784"}]},{"id":"19324","type":"Chemical","text":["creatine"],"offsets":[[1254,1262]],"normalized":[{"db_name":"MESH","db_id":"D003401"}]},{"id":"19325","type":"Disease","text":["Myopathy"],"offsets":[[1315,1323]],"normalized":[{"db_name":"MESH","db_id":"D009135"}]},{"id":"19326","type":"Disease","text":["myoglobinuria"],"offsets":[[1355,1368]],"normalized":[{"db_name":"MESH","db_id":"D009212"}]},{"id":"19327","type":"Disease","text":["renal failure"],"offsets":[[1400,1413]],"normalized":[{"db_name":"MESH","db_id":"D051437"}]},{"id":"19328","type":"Chemical","text":["lovastatin"],"offsets":[[1445,1455]],"normalized":[{"db_name":"MESH","db_id":"D008148"}]},{"id":"19329","type":"Chemical","text":["cyclosporin"],"offsets":[[1507,1518]],"normalized":[{"db_name":"MESH","db_id":"D016572"}]},{"id":"19330","type":"Chemical","text":["gemfibrozil"],"offsets":[[1520,1531]],"normalized":[{"db_name":"MESH","db_id":"D015248"}]},{"id":"19331","type":"Chemical","text":["niacin"],"offsets":[[1535,1541]],"normalized":[{"db_name":"MESH","db_id":"D009525"}]},{"id":"19332","type":"Chemical","text":["Lovastatin"],"offsets":[[1543,1553]],"normalized":[{"db_name":"MESH","db_id":"D008148"}]},{"id":"19333","type":"Chemical","text":["simvastatin"],"offsets":[[1558,1569]],"normalized":[{"db_name":"MESH","db_id":"D019821"}]},{"id":"19334","type":"Chemical","text":["cholesterol"],"offsets":[[1653,1664]],"normalized":[{"db_name":"MESH","db_id":"D002784"}]},{"id":"19335","type":"Disease","text":["hypercholesterolaemia"],"offsets":[[1778,1799]],"normalized":[{"db_name":"MESH","db_id":"D006937"}]}],"events":[],"coreferences":[],"relations":[{"id":"19336","type":"CID","arg1_id":"19330","arg2_id":"19325","normalized":[]},{"id":"19337","type":"CID","arg1_id":"19329","arg2_id":"19325","normalized":[]},{"id":"19338","type":"CID","arg1_id":"19316","arg2_id":"19327","normalized":[]},{"id":"19339","type":"CID","arg1_id":"19318","arg2_id":"19327","normalized":[]},{"id":"19340","type":"CID","arg1_id":"19320","arg2_id":"19327","normalized":[]},{"id":"19341","type":"CID","arg1_id":"19328","arg2_id":"19327","normalized":[]},{"id":"19342","type":"CID","arg1_id":"19332","arg2_id":"19327","normalized":[]},{"id":"19343","type":"CID","arg1_id":"19331","arg2_id":"19325","normalized":[]},{"id":"19344","type":"CID","arg1_id":"19316","arg2_id":"19326","normalized":[]},{"id":"19345","type":"CID","arg1_id":"19318","arg2_id":"19326","normalized":[]},{"id":"19346","type":"CID","arg1_id":"19320","arg2_id":"19326","normalized":[]},{"id":"19347","type":"CID","arg1_id":"19328","arg2_id":"19326","normalized":[]},{"id":"19348","type":"CID","arg1_id":"19332","arg2_id":"19326","normalized":[]}]}
{"id":"19349","document_id":"2894766","passages":[{"id":"19350","type":"title","text":["Sulfasalazine-induced lupus erythematosus."],"offsets":[[0,42]]},{"id":"19351","type":"abstract","text":["Pneumonitis, bilateral pleural effusions, echocardiographic evidence of cardiac tamponade, and positive autoantibodies developed in a 43-year-old man, who was receiving long-term sulfasalazine therapy for chronic ulcerative colitis. After cessation of the sulfasalazine and completion of a six-week course of corticosteroids, these problems resolved over a period of four to six months. It is suggested that the patient had sulfasalazine-induced lupus, which manifested with serositis and pulmonary parenchymal involvement in the absence of joint symptoms. Physicians who use sulfasalazine to treat patients with inflammatory bowel disease should be aware of the signs of sulfasalazine-induced lupus syndrome."],"offsets":[[43,752]]}],"entities":[{"id":"19352","type":"Chemical","text":["Sulfasalazine"],"offsets":[[0,13]],"normalized":[{"db_name":"MESH","db_id":"D012460"}]},{"id":"19353","type":"Disease","text":["lupus erythematosus"],"offsets":[[22,41]],"normalized":[{"db_name":"MESH","db_id":"D008180"}]},{"id":"19354","type":"Disease","text":["Pneumonitis"],"offsets":[[43,54]],"normalized":[{"db_name":"MESH","db_id":"D011014"}]},{"id":"19355","type":"Disease","text":["pleural effusions"],"offsets":[[66,83]],"normalized":[{"db_name":"MESH","db_id":"D010996"}]},{"id":"19356","type":"Disease","text":["cardiac tamponade"],"offsets":[[115,132]],"normalized":[{"db_name":"MESH","db_id":"D002305"}]},{"id":"19357","type":"Chemical","text":["sulfasalazine"],"offsets":[[222,235]],"normalized":[{"db_name":"MESH","db_id":"D012460"}]},{"id":"19358","type":"Disease","text":["ulcerative 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{"id":"19403","document_id":"1549199","passages":[{"id":"19404","type":"title","text":["Optimization of levodopa therapy."],"offsets":[[0,33]]},{"id":"19405","type":"abstract","text":["While there is no single correct starting dose for levodopa therapy, many individuals can be started on either the 25\/100 or controlled-release formula, following the general rule not to attempt to titrate carbidopa-levodopa to the point of \"normality,\" which can lead to toxicity. The physician should also determine the proper use of any adjunctive medications; such combined therapy has become the standard approach to treatment. Following the initial period of therapy, emerging difficulties require a reassessment of therapeutic approaches, such as dosage adjustment or introduction of a dopamine agonist. Other possible adverse effects--such as gastrointestinal disorders, orthostatic hypotension, levodopa-induced psychosis, sleep disturbances or parasomnias, or drug interactions--also require carefully monitored individual treatment. Nonpharmacologic concerns can help the Parkinson's disease patient achieve and maintain optimal functioning, including daily exercise, physical therapy, and involvement with support groups."],"offsets":[[34,1067]]}],"entities":[{"id":"19406","type":"Chemical","text":["levodopa"],"offsets":[[16,24]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"19407","type":"Chemical","text":["levodopa"],"offsets":[[85,93]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"19408","type":"Chemical","text":["carbidopa"],"offsets":[[240,249]],"normalized":[{"db_name":"MESH","db_id":"D002230"}]},{"id":"19409","type":"Chemical","text":["levodopa"],"offsets":[[250,258]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"19410","type":"Disease","text":["toxicity"],"offsets":[[306,314]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"19411","type":"Chemical","text":["dopamine"],"offsets":[[627,635]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"19412","type":"Disease","text":["gastrointestinal disorders"],"offsets":[[685,711]],"normalized":[{"db_name":"MESH","db_id":"D005767"}]},{"id":"19413","type":"Disease","text":["orthostatic hypotension"],"offsets":[[713,736]],"normalized":[{"db_name":"MESH","db_id":"D007024"}]},{"id":"19414","type":"Chemical","text":["levodopa"],"offsets":[[738,746]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"19415","type":"Disease","text":["psychosis"],"offsets":[[755,764]],"normalized":[{"db_name":"MESH","db_id":"D011618"}]},{"id":"19416","type":"Disease","text":["sleep disturbances"],"offsets":[[766,784]],"normalized":[{"db_name":"MESH","db_id":"D012893"}]},{"id":"19417","type":"Disease","text":["parasomnias"],"offsets":[[788,799]],"normalized":[{"db_name":"MESH","db_id":"D020447"}]},{"id":"19418","type":"Disease","text":["Parkinson's disease"],"offsets":[[917,936]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]}],"events":[],"coreferences":[],"relations":[{"id":"19419","type":"CID","arg1_id":"19406","arg2_id":"19417","normalized":[]},{"id":"19420","type":"CID","arg1_id":"19407","arg2_id":"19417","normalized":[]},{"id":"19421","type":"CID","arg1_id":"19409","arg2_id":"19417","normalized":[]},{"id":"19422","type":"CID","arg1_id":"19414","arg2_id":"19417","normalized":[]},{"id":"19423","type":"CID","arg1_id":"19406","arg2_id":"19412","normalized":[]},{"id":"19424","type":"CID","arg1_id":"19407","arg2_id":"19412","normalized":[]},{"id":"19425","type":"CID","arg1_id":"19409","arg2_id":"19412","normalized":[]},{"id":"19426","type":"CID","arg1_id":"19414","arg2_id":"19412","normalized":[]},{"id":"19427","type":"CID","arg1_id":"19406","arg2_id":"19413","normalized":[]},{"id":"19428","type":"CID","arg1_id":"19407","arg2_id":"19413","normalized":[]},{"id":"19429","type":"CID","arg1_id":"19409","arg2_id":"19413","normalized":[]},{"id":"19430","type":"CID","arg1_id":"19414","arg2_id":"19413","normalized":[]}]}
{"id":"19431","document_id":"88336","passages":[{"id":"19432","type":"title","text":["Alpha and beta coma in drug intoxication uncomplicated by cerebral hypoxia."],"offsets":[[0,75]]},{"id":"19433","type":"abstract","text":["Four patients who were rendered comatose or stuporous by drug intoxication, but who were not hypoxic, are described. Three patients received high doses of chlormethiazole for alcohol withdrawal symptoms, and one took a suicidal overdose of nitrazepam. The patient with nitrazepam overdose and two of those with chlormethiazole intoxication conformed to the criteria of 'alpha coma', showing non-reactive generalized or frontally predominant alpha activity in the EEG. The fourth patient who was unconscious after chlormethiazole administration exhibite generalized non-reactive activity in the slow beta range. All four recovered completely without neurological sequelae following the withdrawal of the offending agents. The similarities between the effects of structural lesions and pharmacological depression of the brain stem reticular formation are discussed. It is suggested that in both situations disturbed reticulo-thalamic interactions are important in the pathogenesis of alpha coma. It is concluded that when this electroencephalographic and behavioural picture is seen in drug intoxication, in the absence of significant hypoxaemia, a favourable outcome may be anticipated."],"offsets":[[76,1261]]}],"entities":[{"id":"19434","type":"Disease","text":["coma"],"offsets":[[15,19]],"normalized":[{"db_name":"MESH","db_id":"D003128"}]},{"id":"19435","type":"Disease","text":["cerebral hypoxia"],"offsets":[[58,74]],"normalized":[{"db_name":"MESH","db_id":"D002534"}]},{"id":"19436","type":"Disease","text":["comatose"],"offsets":[[108,116]],"normalized":[{"db_name":"MESH","db_id":"D003128"}]},{"id":"19437","type":"Disease","text":["stuporous"],"offsets":[[120,129]],"normalized":[{"db_name":"MESH","db_id":"D053608"}]},{"id":"19438","type":"Chemical","text":["chlormethiazole"],"offsets":[[231,246]],"normalized":[{"db_name":"MESH","db_id":"D002719"}]},{"id":"19439","type":"Chemical","text":["alcohol"],"offsets":[[251,258]],"normalized":[{"db_name":"MESH","db_id":"D000431"}]},{"id":"19440","type":"Disease","text":["withdrawal symptoms"],"offsets":[[259,278]],"normalized":[{"db_name":"MESH","db_id":"D013375"}]},{"id":"19441","type":"Disease","text":["overdose"],"offsets":[[304,312]],"normalized":[{"db_name":"MESH","db_id":"D062787"}]},{"id":"19442","type":"Chemical","text":["nitrazepam"],"offsets":[[316,326]],"normalized":[{"db_name":"MESH","db_id":"D009567"}]},{"id":"19443","type":"Chemical","text":["nitrazepam"],"offsets":[[345,355]],"normalized":[{"db_name":"MESH","db_id":"D009567"}]},{"id":"19444","type":"Disease","text":["overdose"],"offsets":[[356,364]],"normalized":[{"db_name":"MESH","db_id":"D062787"}]},{"id":"19445","type":"Chemical","text":["chlormethiazole"],"offsets":[[387,402]],"normalized":[{"db_name":"MESH","db_id":"D002719"}]},{"id":"19446","type":"Disease","text":["coma"],"offsets":[[452,456]],"normalized":[{"db_name":"MESH","db_id":"D003128"}]},{"id":"19447","type":"Chemical","text":["chlormethiazole"],"offsets":[[589,604]],"normalized":[{"db_name":"MESH","db_id":"D002719"}]},{"id":"19448","type":"Disease","text":["neurological sequelae"],"offsets":[[725,746]],"normalized":[{"db_name":"MESH","db_id":"D009422"}]},{"id":"19449","type":"Disease","text":["depression"],"offsets":[[876,886]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"19450","type":"Disease","text":["coma"],"offsets":[[1064,1068]],"normalized":[{"db_name":"MESH","db_id":"D003128"}]},{"id":"19451","type":"Disease","text":["hypoxaemia"],"offsets":[[1209,1219]],"normalized":[{"db_name":"MESH","db_id":"D000860"}]}],"events":[],"coreferences":[],"relations":[{"id":"19452","type":"CID","arg1_id":"19438","arg2_id":"19434","normalized":[]},{"id":"19453","type":"CID","arg1_id":"19438","arg2_id":"19436","normalized":[]},{"id":"19454","type":"CID","arg1_id":"19438","arg2_id":"19446","normalized":[]},{"id":"19455","type":"CID","arg1_id":"19438","arg2_id":"19450","normalized":[]},{"id":"19456","type":"CID","arg1_id":"19445","arg2_id":"19434","normalized":[]},{"id":"19457","type":"CID","arg1_id":"19445","arg2_id":"19436","normalized":[]},{"id":"19458","type":"CID","arg1_id":"19445","arg2_id":"19446","normalized":[]},{"id":"19459","type":"CID","arg1_id":"19445","arg2_id":"19450","normalized":[]},{"id":"19460","type":"CID","arg1_id":"19447","arg2_id":"19434","normalized":[]},{"id":"19461","type":"CID","arg1_id":"19447","arg2_id":"19436","normalized":[]},{"id":"19462","type":"CID","arg1_id":"19447","arg2_id":"19446","normalized":[]},{"id":"19463","type":"CID","arg1_id":"19447","arg2_id":"19450","normalized":[]},{"id":"19464","type":"CID","arg1_id":"19442","arg2_id":"19434","normalized":[]},{"id":"19465","type":"CID","arg1_id":"19442","arg2_id":"19436","normalized":[]},{"id":"19466","type":"CID","arg1_id":"19442","arg2_id":"19446","normalized":[]},{"id":"19467","type":"CID","arg1_id":"19442","arg2_id":"19450","normalized":[]},{"id":"19468","type":"CID","arg1_id":"19443","arg2_id":"19434","normalized":[]},{"id":"19469","type":"CID","arg1_id":"19443","arg2_id":"19436","normalized":[]},{"id":"19470","type":"CID","arg1_id":"19443","arg2_id":"19446","normalized":[]},{"id":"19471","type":"CID","arg1_id":"19443","arg2_id":"19450","normalized":[]},{"id":"19472","type":"CID","arg1_id":"19438","arg2_id":"19437","normalized":[]},{"id":"19473","type":"CID","arg1_id":"19445","arg2_id":"19437","normalized":[]},{"id":"19474","type":"CID","arg1_id":"19447","arg2_id":"19437","normalized":[]},{"id":"19475","type":"CID","arg1_id":"19442","arg2_id":"19441","normalized":[]},{"id":"19476","type":"CID","arg1_id":"19442","arg2_id":"19444","normalized":[]},{"id":"19477","type":"CID","arg1_id":"19443","arg2_id":"19441","normalized":[]},{"id":"19478","type":"CID","arg1_id":"19443","arg2_id":"19444","normalized":[]}]}
{"id":"19479","document_id":"18544179","passages":[{"id":"19480","type":"title","text":["Omitting fentanyl reduces nausea and vomiting, without increasing pain, after sevoflurane for day surgery."],"offsets":[[0,106]]},{"id":"19481","type":"abstract","text":["BACKGROUND AND OBJECTIVE: Despite advantages of induction and maintenance of anaesthesia with sevoflurane, postoperative nausea and vomiting occurs frequently. Fentanyl is a commonly used supplement that may contribute to this, although it may also improve analgesia. METHODS: This double-blind study examined the incidence and severity of postoperative nausea and vomiting and pain in the first 24 h after sevoflurane anaesthesia in 216 adult day surgery patients. Patients were randomly allocated to either receive or not receive 1 1 fentanyl, while a third group received dexamethasone in addition to fentanyl. RESULTS: Omission of fentanyl did not reduce the overall incidence of postoperative nausea and vomiting, but did reduce the incidence of vomiting and\/or moderate to severe nausea prior to discharge from 20% and 17% with fentanyl and fentanyl-dexamethasone, respectively, to 5% (P = 0.013). Antiemetic requirements were reduced from 24% and 31% to 7% (P = 0.0012). Dexamethasone had no significant effect on the incidence or severity of postoperative nausea and vomiting. Combining the two fentanyl groups revealed further significant benefits from the avoidance of opioids, reducing postoperative nausea and vomiting and nausea prior to discharge from 35% and 33% to 22% and 19% (P = 0.049 and P = 0.035), respectively, while nausea in the first 24 h was decreased from 42% to 27% (P = 0.034). Pain severity and analgesic requirements were unaffected by the omission of fentanyl. Fentanyl did reduce minor intraoperative movement but had no sevoflurane-sparing effect and increased respiratory depression, hypotension and bradycardia. CONCLUSION: As fentanyl exacerbated postoperative nausea and vomiting without an improvement in postoperative pain and also had adverse cardiorespiratory effects, it appears to be an unnecessary and possibly detrimental supplement to sevoflurane in day surgery."],"offsets":[[107,2017]]}],"entities":[{"id":"19482","type":"Chemical","text":["fentanyl"],"offsets":[[9,17]],"normalized":[{"db_name":"MESH","db_id":"D005283"}]},{"id":"19483","type":"Disease","text":["nausea"],"offsets":[[26,32]],"normalized":[{"db_name":"MESH","db_id":"D009325"}]},{"id":"19484","type":"Disease","text":["vomiting"],"offsets":[[37,45]],"normalized":[{"db_name":"MESH","db_id":"D014839"}]},{"id":"19485","type":"Disease","text":["pain"],"offsets":[[66,70]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"19486","type":"Chemical","text":["sevoflurane"],"offsets":[[78,89]],"normalized":[{"db_name":"MESH","db_id":"C009250"}]},{"id":"19487","type":"Chemical","text":["sevoflurane"],"offsets":[[201,212]],"normalized":[{"db_name":"MESH","db_id":"C009250"}]},{"id":"19488","type":"Disease","text":["postoperative nausea and vomiting"],"offsets":[[214,247]],"normalized":[{"db_name":"MESH","db_id":"D020250"}]},{"id":"19489","type":"Chemical","text":["Fentanyl"],"offsets":[[267,275]],"normalized":[{"db_name":"MESH","db_id":"D005283"}]},{"id":"19490","type":"Disease","text":["postoperative nausea and vomiting"],"offsets":[[447,480]],"normalized":[{"db_name":"MESH","db_id":"D020250"}]},{"id":"19491","type":"Disease","text":["pain"],"offsets":[[485,489]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"19492","type":"Chemical","text":["sevoflurane"],"offsets":[[514,525]],"normalized":[{"db_name":"MESH","db_id":"C009250"}]},{"id":"19493","type":"Chemical","text":["fentanyl"],"offsets":[[643,651]],"normalized":[{"db_name":"MESH","db_id":"D005283"}]},{"id":"19494","type":"Chemical","text":["dexamethasone"],"offsets":[[682,695]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"19495","type":"Chemical","text":["fentanyl"],"offsets":[[711,719]],"normalized":[{"db_name":"MESH","db_id":"D005283"}]},{"id":"19496","type":"Chemical","text":["fentanyl"],"offsets":[[742,750]],"normalized":[{"db_name":"MESH","db_id":"D005283"}]},{"id":"19497","type":"Disease","text":["postoperative nausea and vomiting"],"offsets":[[791,824]],"normalized":[{"db_name":"MESH","db_id":"D020250"}]},{"id":"19498","type":"Disease","text":["vomiting"],"offsets":[[858,866]],"normalized":[{"db_name":"MESH","db_id":"D014839"}]},{"id":"19499","type":"Disease","text":["nausea"],"offsets":[[893,899]],"normalized":[{"db_name":"MESH","db_id":"D009325"}]},{"id":"19500","type":"Chemical","text":["fentanyl"],"offsets":[[941,949]],"normalized":[{"db_name":"MESH","db_id":"D005283"}]},{"id":"19501","type":"Chemical","text":["fentanyl"],"offsets":[[954,962]],"normalized":[{"db_name":"MESH","db_id":"D005283"}]},{"id":"19502","type":"Chemical","text":["dexamethasone"],"offsets":[[963,976]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"19503","type":"Chemical","text":["Dexamethasone"],"offsets":[[1085,1098]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"19504","type":"Disease","text":["postoperative nausea and 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{"id":"19619","document_id":"18186898","passages":[{"id":"19620","type":"title","text":["Renal Fanconi syndrome and myopathy after liver transplantation: drug-related mitochondrial cytopathy?"],"offsets":[[0,102]]},{"id":"19621","type":"abstract","text":["Advances in the field of transplantation provide a better quality of life and allow more favorable conditions for growth and development in children. However, combinations of different therapeutic regimens require consideration of potential adverse reactions. We describe a 15-yr-old girl who had orthotopic liver transplantation because of Wilson's disease. Tacrolimus, MMF, and steroids were given as immunosuppressant. Lamivudine was added because of de nova hepatitis B infection during her follow-up. Three yr after transplantation she developed renal Fanconi syndrome with severe metabolic acidosis, hypophosphatemia, glycosuria, and aminoaciduria. Although tacrolimus was suspected to be the cause of late post-transplant renal acidosis and was replaced by sirolimus, acidosis, and electrolyte imbalance got worse. Proximal muscle weakness has developed during her follow-up. Fanconi syndrome, as well as myopathy, is well recognized in patients with mitochondrial disorders and caused by depletion of mtDNA. We suggest that our patient's tubular dysfunction and myopathy may have resulted from mitochondrial dysfunction which is triggered by tacrolimus and augmented by lamivudine."],"offsets":[[103,1292]]}],"entities":[{"id":"19622","type":"Disease","text":["Renal Fanconi syndrome"],"offsets":[[0,22]],"normalized":[{"db_name":"MESH","db_id":"D005198"}]},{"id":"19623","type":"Disease","text":["myopathy"],"offsets":[[27,35]],"normalized":[{"db_name":"MESH","db_id":"D009135"}]},{"id":"19624","type":"Disease","text":["mitochondrial cytopathy"],"offsets":[[78,101]],"normalized":[{"db_name":"MESH","db_id":"C540770"}]},{"id":"19625","type":"Disease","text":["Wilson's 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{"id":"19684","document_id":"16867021","passages":[{"id":"19685","type":"title","text":["Antipsychotic-like profile of thioperamide, a selective H3-receptor antagonist in mice."],"offsets":[[0,87]]},{"id":"19686","type":"abstract","text":["Experimental and clinical evidence points to a role of central histaminergic system in the pathogenesis of schizophrenia. The present study was designed to study the effect of histamine H(3)-receptor ligands on neuroleptic-induced catalepsy, apomorphine-induced climbing behavior and amphetamine-induced locomotor activities in mice. Catalepsy was induced by haloperidol (2 mg\/kg p.o.), while apomorphine (1.5 mg\/kg s.c.) and amphetamine (2 mg\/kg s.c.) were used for studying climbing behavior and locomotor activities, respectively. (R)-alpha-methylhistamine (RAMH) (5 microg i.c.v.) and thioperamide (THP) (15 mg\/kg i.p.), per se did not cause catalepsy. Administration of THP (3.75, 7.5 and 15 mg\/kg i.p.) 1 h prior to haloperidol resulted in a dose-dependent increase in the catalepsy times (P < 0.05). However, pretreatment with RAMH significantly reversed such an effect of THP (15 mg\/kg i.p.). RAMH per se showed significant reduction in locomotor time, distance traveled and average speed but THP (15 mg\/kg i.p.) per se had no effect on these parameters. On amphetamine-induced hyperactivity, THP (3.75 and 7.5 mg\/kg i.p.) reduced locomotor time, distance traveled and average speed (P < 0.05). Pretreatment with RAMH (5 microg i.c.v.) could partially reverse such effects of THP (3.75 mg\/kg i.p.). Climbing behavior induced by apomorphine was reduced in animals treated with THP. Such an effect was, however, reversed in presence of RAMH. THP exhibited an antipsychotic-like profile by potentiating haloperidol-induced catalepsy, reducing amphetamine-induced hyperactivity and reducing apomorphine-induced climbing in mice. Such effects of THP were reversed by RAMH indicating the involvement of histamine H(3)-receptors. Findings suggest a potential for H(3)-receptor antagonists in improving the refractory cases of 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{"id":"19805","document_id":"14976857","passages":[{"id":"19806","type":"title","text":["Transient platypnea-orthodeoxia-like syndrome induced by propafenone overdose in a young woman with Ebstein's anomaly."],"offsets":[[0,118]]},{"id":"19807","type":"abstract","text":["In this report we describe the case of a 37-year-old white woman with Ebstein's anomaly, who developed a rare syndrome called platypnea-orthodeoxia, characterized by massive right-to-left interatrial shunting with transient profound hypoxia and cyanosis. This shunt of blood via a patent foramen ovale occurred in the presence of a normal pulmonary artery pressure, and was probably precipitated by a propafenone overdose. This drug caused biventricular dysfunction, due to its negative inotropic effect, and hypotension, due to its peripheral vasodilatory effect. These effects gave rise to an increase in the right atrial pressure and a decrease in the left one with a consequent stretching of the foramen ovale and the creation of massive right-to-left shunting. In our case this interatrial shunt was very accurately detected at bubble contrast echocardiography."],"offsets":[[119,985]]}],"entities":[{"id":"19808","type":"Disease","text":["platypnea-orthodeoxia-like syndrome"],"offsets":[[10,45]],"normalized":[]},{"id":"19809","type":"Chemical","text":["propafenone"],"offsets":[[57,68]],"normalized":[{"db_name":"MESH","db_id":"D011405"}]},{"id":"19810","type":"Disease","text":["overdose"],"offsets":[[69,77]],"normalized":[{"db_name":"MESH","db_id":"D062787"}]},{"id":"19811","type":"Disease","text":["Ebstein's anomaly"],"offsets":[[100,117]],"normalized":[{"db_name":"MESH","db_id":"D004437"}]},{"id":"19812","type":"Disease","text":["Ebstein's anomaly"],"offsets":[[189,206]],"normalized":[{"db_name":"MESH","db_id":"D004437"}]},{"id":"19813","type":"Disease","text":["platypnea-orthodeoxia"],"offsets":[[245,266]],"normalized":[]},{"id":"19814","type":"Disease","text":["hypoxia"],"offsets":[[352,359]],"normalized":[{"db_name":"MESH","db_id":"D000860"}]},{"id":"19815","type":"Disease","text":["cyanosis"],"offsets":[[364,372]],"normalized":[{"db_name":"MESH","db_id":"D003490"}]},{"id":"19816","type":"Disease","text":["patent foramen ovale"],"offsets":[[400,420]],"normalized":[{"db_name":"MESH","db_id":"D054092"}]},{"id":"19817","type":"Chemical","text":["propafenone"],"offsets":[[520,531]],"normalized":[{"db_name":"MESH","db_id":"D011405"}]},{"id":"19818","type":"Disease","text":["overdose"],"offsets":[[532,540]],"normalized":[{"db_name":"MESH","db_id":"D062787"}]},{"id":"19819","type":"Disease","text":["biventricular dysfunction"],"offsets":[[559,584]],"normalized":[{"db_name":"MESH","db_id":"D018754"}]},{"id":"19820","type":"Disease","text":["hypotension"],"offsets":[[628,639]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]}],"events":[],"coreferences":[],"relations":[{"id":"19821","type":"CID","arg1_id":"19809","arg2_id":"19819","normalized":[]},{"id":"19822","type":"CID","arg1_id":"19817","arg2_id":"19819","normalized":[]},{"id":"19823","type":"CID","arg1_id":"19809","arg2_id":"19814","normalized":[]},{"id":"19824","type":"CID","arg1_id":"19817","arg2_id":"19814","normalized":[]},{"id":"19825","type":"CID","arg1_id":"19809","arg2_id":"19815","normalized":[]},{"id":"19826","type":"CID","arg1_id":"19817","arg2_id":"19815","normalized":[]}]}
{"id":"19827","document_id":"11745184","passages":[{"id":"19828","type":"title","text":["A Phase II trial of cisplatin plus WR-2721 (amifostine) for metastatic breast carcinoma: an Eastern Cooperative Oncology Group Study (E8188)."],"offsets":[[0,141]]},{"id":"19829","type":"abstract","text":["BACKGROUND: Cisplatin has minimal antitumor activity when used as second- or third-line treatment of metastatic breast carcinoma. Older reports suggest an objective response rate of 8% when 60-120 mg\/m2 of cisplatin is administered every 3-4 weeks. Although a dose-response effect has been observed with cisplatin, the dose-limiting toxicities associated with cisplatin (e.g., nephrotoxicity, ototoxicity, and neurotoxicity) have limited its use as a treatment for breast carcinoma. WR-2721 or amifostine initially was developed to protect military personnel in the event of nuclear war. Amifostine subsequently was shown to protect normal tissues from the toxic effects of alkylating agents and cisplatin without decreasing the antitumor effect of the chemotherapy. Early trials of cisplatin and amifostine also suggested that the incidence and severity of cisplatin-induced nephrotoxicity, ototoxicity, and neuropathy were reduced. METHODS: A Phase II study of the combination of cisplatin plus amifostine was conducted in patients with progressive metastatic breast carcinoma who had received one, but not more than one, chemotherapy regimen for metastatic disease. Patients received amifostine, 910 mg\/m2 intravenously over 15 minutes. After completion of the amifostine infusion, cisplatin 120 mg\/m2 was administered over 30 minutes. Intravenous hydration and mannitol was administered before and after cisplatin. Treatment was administered every 3 weeks until disease progression. RESULTS: Forty-four patients were enrolled in the study of which 7 (16%) were ineligible. A median of 2 cycles of therapy was administered to the 37 eligible patients. Six partial responses were observed for an overall response rate of 16%. Most patients (57%) stopped treatment because of disease progression. Neurologic toxicity was reported in 52% of patients. Seven different life-threatening toxicities were observed in patients while receiving treatment. CONCLUSIONS: The combination of cisplatin and amifostine in this study resulted in an overall response rate of 16%. Neither a tumor-protective effect nor reduced toxicity to normal tissues was observed with the addition of amifostine to cisplatin in this trial."],"offsets":[[142,2351]]}],"entities":[{"id":"19830","type":"Chemical","text":["cisplatin"],"offsets":[[20,29]],"normalized":[{"db_name":"MESH","db_id":"D002945"}]},{"id":"19831","type":"Chemical","text":["WR-2721"],"offsets":[[35,42]],"normalized":[{"db_name":"MESH","db_id":"D004999"}]},{"id":"19832","type":"Chemical","text":["amifostine"],"offsets":[[44,54]],"normalized":[{"db_name":"MESH","db_id":"D004999"}]},{"id":"19833","type":"Disease","text":["breast carcinoma"],"offsets":[[71,87]],"normalized":[{"db_name":"MESH","db_id":"D001943"}]},{"id":"19834","type":"Chemical","text":["Cisplatin"],"offsets":[[154,163]],"normalized":[{"db_name":"MESH","db_id":"D002945"}]},{"id":"19835","type":"Disease","text":["breast 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{"id":"19977","document_id":"3750012","passages":[{"id":"19978","type":"title","text":["Myasthenia gravis caused by penicillamine and chloroquine therapy for rheumatoid arthritis."],"offsets":[[0,91]]},{"id":"19979","type":"abstract","text":["We have described a unique patient who had reversible and dose-related myasthenia gravis after penicillamine and chloroquine therapy for rheumatoid arthritis. Although acetylcholine receptor antibodies were not detectable, the time course was consistent with an autoimmune process."],"offsets":[[92,373]]}],"entities":[{"id":"19980","type":"Disease","text":["Myasthenia gravis"],"offsets":[[0,17]],"normalized":[{"db_name":"MESH","db_id":"D009157"}]},{"id":"19981","type":"Chemical","text":["penicillamine"],"offsets":[[28,41]],"normalized":[{"db_name":"MESH","db_id":"D010396"}]},{"id":"19982","type":"Chemical","text":["chloroquine"],"offsets":[[46,57]],"normalized":[{"db_name":"MESH","db_id":"D002738"}]},{"id":"19983","type":"Disease","text":["rheumatoid arthritis"],"offsets":[[70,90]],"normalized":[{"db_name":"MESH","db_id":"D001172"}]},{"id":"19984","type":"Disease","text":["myasthenia gravis"],"offsets":[[163,180]],"normalized":[{"db_name":"MESH","db_id":"D009157"}]},{"id":"19985","type":"Chemical","text":["penicillamine"],"offsets":[[187,200]],"normalized":[{"db_name":"MESH","db_id":"D010396"}]},{"id":"19986","type":"Chemical","text":["chloroquine"],"offsets":[[205,216]],"normalized":[{"db_name":"MESH","db_id":"D002738"}]},{"id":"19987","type":"Disease","text":["rheumatoid arthritis"],"offsets":[[229,249]],"normalized":[{"db_name":"MESH","db_id":"D001172"}]},{"id":"19988","type":"Chemical","text":["acetylcholine"],"offsets":[[260,273]],"normalized":[{"db_name":"MESH","db_id":"D000109"}]}],"events":[],"coreferences":[],"relations":[{"id":"19989","type":"CID","arg1_id":"19982","arg2_id":"19980","normalized":[]},{"id":"19990","type":"CID","arg1_id":"19982","arg2_id":"19984","normalized":[]},{"id":"19991","type":"CID","arg1_id":"19986","arg2_id":"19980","normalized":[]},{"id":"19992","type":"CID","arg1_id":"19986","arg2_id":"19984","normalized":[]},{"id":"19993","type":"CID","arg1_id":"19981","arg2_id":"19980","normalized":[]},{"id":"19994","type":"CID","arg1_id":"19981","arg2_id":"19984","normalized":[]},{"id":"19995","type":"CID","arg1_id":"19985","arg2_id":"19980","normalized":[]},{"id":"19996","type":"CID","arg1_id":"19985","arg2_id":"19984","normalized":[]}]}
{"id":"19997","document_id":"1130930","passages":[{"id":"19998","type":"title","text":["Nephrotoxicity of combined cephalothin-gentamicin regimen."],"offsets":[[0,58]]},{"id":"19999","type":"abstract","text":["Two patients developed acute tubular necrosis, characterized clinically by acute oliguric renal failure, while they were receiving a combination of cephalothin sodium and gentamicin sulfate therapy. Patients who are given this drug regimen should be observed very carefully for early signs of nephrotoxicity. High doses of this antibiotic combination should be avoided especially in elderly patients. Patients with renal insufficiency should not be given this regimen."],"offsets":[[59,527]]}],"entities":[{"id":"20000","type":"Disease","text":["Nephrotoxicity"],"offsets":[[0,14]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"20001","type":"Chemical","text":["cephalothin"],"offsets":[[27,38]],"normalized":[{"db_name":"MESH","db_id":"D002512"}]},{"id":"20002","type":"Chemical","text":["gentamicin"],"offsets":[[39,49]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"20003","type":"Disease","text":["acute tubular necrosis"],"offsets":[[82,104]],"normalized":[{"db_name":"MESH","db_id":"D007683"}]},{"id":"20004","type":"Disease","text":["oliguric renal failure"],"offsets":[[140,162]],"normalized":[{"db_name":"MESH","db_id":"D009846"},{"db_name":"MESH","db_id":"D051437"}]},{"id":"20005","type":"Disease","text":["oliguric"],"offsets":[[140,148]],"normalized":[{"db_name":"MESH","db_id":"D009846"}]},{"id":"20006","type":"Disease","text":["renal failure"],"offsets":[[149,162]],"normalized":[{"db_name":"MESH","db_id":"D051437"}]},{"id":"20007","type":"Chemical","text":["cephalothin sodium"],"offsets":[[207,225]],"normalized":[{"db_name":"MESH","db_id":"D002512"}]},{"id":"20008","type":"Chemical","text":["gentamicin sulfate"],"offsets":[[230,248]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"20009","type":"Disease","text":["nephrotoxicity"],"offsets":[[352,366]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"20010","type":"Disease","text":["renal insufficiency"],"offsets":[[474,493]],"normalized":[{"db_name":"MESH","db_id":"D051437"}]}],"events":[],"coreferences":[],"relations":[{"id":"20011","type":"CID","arg1_id":"20002","arg2_id":"20003","normalized":[]},{"id":"20012","type":"CID","arg1_id":"20008","arg2_id":"20003","normalized":[]},{"id":"20013","type":"CID","arg1_id":"20001","arg2_id":"20003","normalized":[]},{"id":"20014","type":"CID","arg1_id":"20007","arg2_id":"20003","normalized":[]},{"id":"20015","type":"CID","arg1_id":"20002","arg2_id":"20004","normalized":[]},{"id":"20016","type":"CID","arg1_id":"20002","arg2_id":"20005","normalized":[]},{"id":"20017","type":"CID","arg1_id":"20008","arg2_id":"20004","normalized":[]},{"id":"20018","type":"CID","arg1_id":"20008","arg2_id":"20005","normalized":[]},{"id":"20019","type":"CID","arg1_id":"20001","arg2_id":"20004","normalized":[]},{"id":"20020","type":"CID","arg1_id":"20001","arg2_id":"20005","normalized":[]},{"id":"20021","type":"CID","arg1_id":"20007","arg2_id":"20004","normalized":[]},{"id":"20022","type":"CID","arg1_id":"20007","arg2_id":"20005","normalized":[]}]}
{"id":"20023","document_id":"19356307","passages":[{"id":"20024","type":"title","text":["Components of lemon essential oil attenuate dementia induced by scopolamine."],"offsets":[[0,76]]},{"id":"20025","type":"abstract","text":["The anti-dementia effects of s-limonene and s-perillyl alcohol were observed using the passive avoidance test (PA) and the open field habituation test (OFH). These lemon essential oils showed strong ability to improve memory impaired by scopolamine; however, s-perillyl alcohol relieved the deficit of associative memory in PA only, and did not improve non-associative memory significantly in OFH. Analysis of neurotransmitter concentration in some brain regions on the test day showed that dopamine concentration of the vehicle\/scopolamine group was significantly lower than that of the vehicle\/vehicle group, but this phenomenon was reversed when s-limonene or s-perillyl alcohol were administered before the injection of scopolamine. Simultaneously, we found that these two lemon essential oil components could inhibit acetylcholinesterase activity in vitro using the Ellman method."],"offsets":[[77,962]]}],"entities":[{"id":"20026","type":"Disease","text":["dementia"],"offsets":[[44,52]],"normalized":[{"db_name":"MESH","db_id":"D003704"}]},{"id":"20027","type":"Chemical","text":["scopolamine"],"offsets":[[64,75]],"normalized":[{"db_name":"MESH","db_id":"D012601"}]},{"id":"20028","type":"Disease","text":["dementia"],"offsets":[[86,94]],"normalized":[{"db_name":"MESH","db_id":"D003704"}]},{"id":"20029","type":"Chemical","text":["s-limonene"],"offsets":[[106,116]],"normalized":[{"db_name":"MESH","db_id":"C008281"}]},{"id":"20030","type":"Chemical","text":["s-perillyl alcohol"],"offsets":[[121,139]],"normalized":[{"db_name":"MESH","db_id":"C032208"}]},{"id":"20031","type":"Disease","text":["memory impaired"],"offsets":[[295,310]],"normalized":[{"db_name":"MESH","db_id":"D008569"}]},{"id":"20032","type":"Chemical","text":["scopolamine"],"offsets":[[314,325]],"normalized":[{"db_name":"MESH","db_id":"D012601"}]},{"id":"20033","type":"Chemical","text":["s-perillyl alcohol"],"offsets":[[336,354]],"normalized":[{"db_name":"MESH","db_id":"C032208"}]},{"id":"20034","type":"Disease","text":["deficit of associative memory"],"offsets":[[368,397]],"normalized":[{"db_name":"MESH","db_id":"D008569"}]},{"id":"20035","type":"Chemical","text":["dopamine"],"offsets":[[568,576]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"20036","type":"Chemical","text":["scopolamine"],"offsets":[[606,617]],"normalized":[{"db_name":"MESH","db_id":"D012601"}]},{"id":"20037","type":"Chemical","text":["s-limonene"],"offsets":[[726,736]],"normalized":[{"db_name":"MESH","db_id":"C008281"}]},{"id":"20038","type":"Chemical","text":["s-perillyl alcohol"],"offsets":[[740,758]],"normalized":[{"db_name":"MESH","db_id":"C032208"}]},{"id":"20039","type":"Chemical","text":["scopolamine"],"offsets":[[801,812]],"normalized":[{"db_name":"MESH","db_id":"D012601"}]}],"events":[],"coreferences":[],"relations":[{"id":"20040","type":"CID","arg1_id":"20027","arg2_id":"20031","normalized":[]},{"id":"20041","type":"CID","arg1_id":"20027","arg2_id":"20034","normalized":[]},{"id":"20042","type":"CID","arg1_id":"20032","arg2_id":"20031","normalized":[]},{"id":"20043","type":"CID","arg1_id":"20032","arg2_id":"20034","normalized":[]},{"id":"20044","type":"CID","arg1_id":"20036","arg2_id":"20031","normalized":[]},{"id":"20045","type":"CID","arg1_id":"20036","arg2_id":"20034","normalized":[]},{"id":"20046","type":"CID","arg1_id":"20039","arg2_id":"20031","normalized":[]},{"id":"20047","type":"CID","arg1_id":"20039","arg2_id":"20034","normalized":[]}]}
{"id":"20048","document_id":"15957009","passages":[{"id":"20049","type":"title","text":["The selective 5-HT6 receptor antagonist Ro4368554 restores memory performance in cholinergic and serotonergic models of memory deficiency in the rat."],"offsets":[[0,149]]},{"id":"20050","type":"abstract","text":["Antagonists at serotonin type 6 (5-HT(6)) receptors show activity in models of learning and memory. Although the underlying mechanism(s) are not well understood, these effects may involve an increase in acetylcholine (ACh) levels. The present study sought to characterize the cognitive-enhancing effects of the 5-HT(6) antagonist Ro4368554 (3-benzenesulfonyl-7-(4-methyl-piperazin-1-yl)1H-indole) in a rat object recognition task employing a cholinergic (scopolamine pretreatment) and a serotonergic- (tryptophan (TRP) depletion) deficient model, and compared its pattern of action with that of the acetylcholinesterase inhibitor metrifonate. Initial testing in a time-dependent forgetting task employing a 24-h delay between training and testing showed that metrifonate improved object recognition (at 10 and 30 mg\/kg, p.o.), whereas Ro4368554 was inactive. Both, Ro4368554 (3 and 10 mg\/kg, intraperitoneally (i.p.)) and metrifonate (10 mg\/kg, p.o., respectively) reversed memory deficits induced by scopolamine and TRP depletion (10 mg\/kg, i.p., and 3 mg\/kg, p.o., respectively). In conclusion, although Ro4368554 did not improve a time-related retention deficit, it reversed a cholinergic and a serotonergic memory deficit, suggesting that both mechanisms may be involved in the facilitation of object memory by Ro4368554 and, possibly, other 5-HT(6) receptor antagonists."],"offsets":[[150,1525]]}],"entities":[{"id":"20051","type":"Chemical","text":["Ro4368554"],"offsets":[[40,49]],"normalized":[{"db_name":"MESH","db_id":"C507242"}]},{"id":"20052","type":"Disease","text":["memory deficiency"],"offsets":[[120,137]],"normalized":[{"db_name":"MESH","db_id":"D008569"}]},{"id":"20053","type":"Chemical","text":["serotonin"],"offsets":[[165,174]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"20054","type":"Chemical","text":["5-HT"],"offsets":[[183,187]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"20055","type":"Chemical","text":["acetylcholine"],"offsets":[[353,366]],"normalized":[{"db_name":"MESH","db_id":"D000109"}]},{"id":"20056","type":"Chemical","text":["ACh"],"offsets":[[368,371]],"normalized":[{"db_name":"MESH","db_id":"D000109"}]},{"id":"20057","type":"Chemical","text":["5-HT"],"offsets":[[461,465]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"20058","type":"Chemical","text":["Ro4368554"],"offsets":[[480,489]],"normalized":[{"db_name":"MESH","db_id":"C507242"}]},{"id":"20059","type":"Chemical","text":["3-benzenesulfonyl-7-(4-methyl-piperazin-1-yl)1H-indole"],"offsets":[[491,545]],"normalized":[{"db_name":"MESH","db_id":"C507242"}]},{"id":"20060","type":"Chemical","text":["scopolamine"],"offsets":[[605,616]],"normalized":[{"db_name":"MESH","db_id":"D012601"}]},{"id":"20061","type":"Chemical","text":["tryptophan"],"offsets":[[652,662]],"normalized":[{"db_name":"MESH","db_id":"D014364"}]},{"id":"20062","type":"Chemical","text":["TRP"],"offsets":[[664,667]],"normalized":[{"db_name":"MESH","db_id":"D014364"}]},{"id":"20063","type":"Chemical","text":["metrifonate"],"offsets":[[780,791]],"normalized":[{"db_name":"MESH","db_id":"D014236"}]},{"id":"20064","type":"Chemical","text":["metrifonate"],"offsets":[[909,920]],"normalized":[{"db_name":"MESH","db_id":"D014236"}]},{"id":"20065","type":"Chemical","text":["Ro4368554"],"offsets":[[985,994]],"normalized":[{"db_name":"MESH","db_id":"C507242"}]},{"id":"20066","type":"Chemical","text":["Ro4368554"],"offsets":[[1015,1024]],"normalized":[{"db_name":"MESH","db_id":"C507242"}]},{"id":"20067","type":"Chemical","text":["metrifonate"],"offsets":[[1072,1083]],"normalized":[{"db_name":"MESH","db_id":"D014236"}]},{"id":"20068","type":"Disease","text":["memory deficits"],"offsets":[[1124,1139]],"normalized":[{"db_name":"MESH","db_id":"D008569"}]},{"id":"20069","type":"Chemical","text":["scopolamine"],"offsets":[[1151,1162]],"normalized":[{"db_name":"MESH","db_id":"D012601"}]},{"id":"20070","type":"Chemical","text":["TRP"],"offsets":[[1167,1170]],"normalized":[{"db_name":"MESH","db_id":"D014364"}]},{"id":"20071","type":"Chemical","text":["Ro4368554"],"offsets":[[1256,1265]],"normalized":[{"db_name":"MESH","db_id":"C507242"}]},{"id":"20072","type":"Disease","text":["memory deficit"],"offsets":[[1361,1375]],"normalized":[{"db_name":"MESH","db_id":"D008569"}]},{"id":"20073","type":"Chemical","text":["Ro4368554"],"offsets":[[1465,1474]],"normalized":[{"db_name":"MESH","db_id":"C507242"}]},{"id":"20074","type":"Chemical","text":["5-HT"],"offsets":[[1496,1500]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]}],"events":[],"coreferences":[],"relations":[{"id":"20075","type":"CID","arg1_id":"20060","arg2_id":"20052","normalized":[]},{"id":"20076","type":"CID","arg1_id":"20060","arg2_id":"20068","normalized":[]},{"id":"20077","type":"CID","arg1_id":"20060","arg2_id":"20072","normalized":[]},{"id":"20078","type":"CID","arg1_id":"20069","arg2_id":"20052","normalized":[]},{"id":"20079","type":"CID","arg1_id":"20069","arg2_id":"20068","normalized":[]},{"id":"20080","type":"CID","arg1_id":"20069","arg2_id":"20072","normalized":[]}]}
{"id":"20081","document_id":"15899738","passages":[{"id":"20082","type":"title","text":["Lone atrial fibrillation associated with creatine monohydrate supplementation."],"offsets":[[0,78]]},{"id":"20083","type":"abstract","text":["Atrial fibrillation in young patients without structural heart disease is rare. Therefore, when the arrhythmia is present in this population, reversible causes must be identified and resolved. Thyroid disorders, illicit drug or stimulant use, and acute alcohol intoxication are among these causes. We report the case of a 30-year-old Caucasian man who came to the emergency department in atrial fibrillation with rapid ventricular response. His medical history was unremarkable, except for minor fractures of the fingers and foot. Thyroid-stimulating hormone, magnesium, and potassium levels were within normal limits, urine drug screen was negative, and alcohol use was denied. However, when the patient was questioned about use of herbal products and supplements, the use of creatine monohydrate was revealed. The patient was admitted to the hospital, anticoagulated with unfractionated heparin, and given intravenous diltiazem for rate control and intravenous amiodarone for rate and rhythm control. When discharged less than 24 hours later, he was receiving metoprolol and aspirin, with follow-up plans for echocardiography and nuclear imaging to assess perfusion. Exogenous creatine is used by athletes to theoretically improve exercise performance. Vegetarians may also take creatine to replace what they are not consuming from meat, fish, and other animal products. Previous anecdotal reports have linked creatine to the development of arrhythmia. Clinicians must be diligent when interviewing patients about their drug therapy histories and include questions about their use of herbal products and dietary supplements. In addition, it is important to report adverse effects associated with frequently consumed supplements and herbal products to the Food and Drug Administration and in the literature."],"offsets":[[79,1887]]}],"entities":[{"id":"20084","type":"Disease","text":["atrial fibrillation"],"offsets":[[5,24]],"normalized":[{"db_name":"MESH","db_id":"D001281"}]},{"id":"20085","type":"Chemical","text":["creatine"],"offsets":[[41,49]],"normalized":[{"db_name":"MESH","db_id":"D003401"}]},{"id":"20086","type":"Disease","text":["Atrial fibrillation"],"offsets":[[79,98]],"normalized":[{"db_name":"MESH","db_id":"D001281"}]},{"id":"20087","type":"Disease","text":["heart disease"],"offsets":[[136,149]],"normalized":[{"db_name":"MESH","db_id":"D006331"}]},{"id":"20088","type":"Disease","text":["arrhythmia"],"offsets":[[179,189]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"20089","type":"Disease","text":["Thyroid disorders"],"offsets":[[272,289]],"normalized":[{"db_name":"MESH","db_id":"D013959"}]},{"id":"20090","type":"Disease","text":["acute alcohol intoxication"],"offsets":[[326,352]],"normalized":[{"db_name":"MESH","db_id":"D000435"}]},{"id":"20091","type":"Disease","text":["atrial fibrillation"],"offsets":[[467,486]],"normalized":[{"db_name":"MESH","db_id":"D001281"}]},{"id":"20092","type":"Disease","text":["fractures"],"offsets":[[575,584]],"normalized":[{"db_name":"MESH","db_id":"D050723"}]},{"id":"20093","type":"Chemical","text":["magnesium"],"offsets":[[639,648]],"normalized":[{"db_name":"MESH","db_id":"D008274"}]},{"id":"20094","type":"Chemical","text":["potassium"],"offsets":[[654,663]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"20095","type":"Chemical","text":["alcohol"],"offsets":[[734,741]],"normalized":[{"db_name":"MESH","db_id":"D000431"}]},{"id":"20096","type":"Chemical","text":["creatine"],"offsets":[[856,864]],"normalized":[{"db_name":"MESH","db_id":"D003401"}]},{"id":"20097","type":"Chemical","text":["heparin"],"offsets":[[968,975]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"20098","type":"Chemical","text":["diltiazem"],"offsets":[[999,1008]],"normalized":[{"db_name":"MESH","db_id":"D004110"}]},{"id":"20099","type":"Chemical","text":["amiodarone"],"offsets":[[1042,1052]],"normalized":[{"db_name":"MESH","db_id":"D000638"}]},{"id":"20100","type":"Chemical","text":["metoprolol"],"offsets":[[1141,1151]],"normalized":[{"db_name":"MESH","db_id":"D008790"}]},{"id":"20101","type":"Chemical","text":["aspirin"],"offsets":[[1156,1163]],"normalized":[{"db_name":"MESH","db_id":"D001241"}]},{"id":"20102","type":"Chemical","text":["creatine"],"offsets":[[1258,1266]],"normalized":[{"db_name":"MESH","db_id":"D003401"}]},{"id":"20103","type":"Chemical","text":["creatine"],"offsets":[[1360,1368]],"normalized":[{"db_name":"MESH","db_id":"D003401"}]},{"id":"20104","type":"Chemical","text":["creatine"],"offsets":[[1491,1499]],"normalized":[{"db_name":"MESH","db_id":"D003401"}]},{"id":"20105","type":"Disease","text":["arrhythmia"],"offsets":[[1522,1532]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]}],"events":[],"coreferences":[],"relations":[{"id":"20106","type":"CID","arg1_id":"20085","arg2_id":"20084","normalized":[]},{"id":"20107","type":"CID","arg1_id":"20085","arg2_id":"20086","normalized":[]},{"id":"20108","type":"CID","arg1_id":"20085","arg2_id":"20091","normalized":[]},{"id":"20109","type":"CID","arg1_id":"20096","arg2_id":"20084","normalized":[]},{"id":"20110","type":"CID","arg1_id":"20096","arg2_id":"20086","normalized":[]},{"id":"20111","type":"CID","arg1_id":"20096","arg2_id":"20091","normalized":[]},{"id":"20112","type":"CID","arg1_id":"20102","arg2_id":"20084","normalized":[]},{"id":"20113","type":"CID","arg1_id":"20102","arg2_id":"20086","normalized":[]},{"id":"20114","type":"CID","arg1_id":"20102","arg2_id":"20091","normalized":[]},{"id":"20115","type":"CID","arg1_id":"20103","arg2_id":"20084","normalized":[]},{"id":"20116","type":"CID","arg1_id":"20103","arg2_id":"20086","normalized":[]},{"id":"20117","type":"CID","arg1_id":"20103","arg2_id":"20091","normalized":[]},{"id":"20118","type":"CID","arg1_id":"20104","arg2_id":"20084","normalized":[]},{"id":"20119","type":"CID","arg1_id":"20104","arg2_id":"20086","normalized":[]},{"id":"20120","type":"CID","arg1_id":"20104","arg2_id":"20091","normalized":[]}]}
{"id":"20121","document_id":"15863244","passages":[{"id":"20122","type":"title","text":["Comparison of developmental toxicity of selective and non-selective cyclooxygenase-2 inhibitors in CRL:(WI)WUBR Wistar rats--DFU and piroxicam study."],"offsets":[[0,149]]},{"id":"20123","type":"abstract","text":["BACKGROUND: Cyclooxygenase (COX) inhibitors are one of the most often ingested drugs during pregnancy. Unlike general toxicity data, their prenatal toxic effects were not extensively studied before. The aim of the experiment was to evaluate the developmental toxicity of the non-selective (piroxicam) and selective (DFU; 5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl) phenyl-2(5H)-furanon) COX-2 inhibitors. METHODS: Drugs were separately, orally once daily dosed to pregnant rats from day 8 to 21 (GD1=plug day). Doses were set at 0.3, 3.0 and 30.0mg\/kg for piroxicam and 0.2, 2.0 and 20.0mg\/kg for DFU. Fetuses were delivered on GD 21 and routinely examined. Comprehensive clinical and developmental measurements were done. The pooled statistical analysis for ventricular septal (VSD) and midline (MD) defects was performed for rat fetuses exposed to piroxicam, selective and non-selective COX-2 inhibitor based on present and historic data. RESULTS: Maternal toxicity, intrauterine growth retardation, and increase of external and skeletal variations were found in rats treated with the highest dose of piroxicam. Decrease of fetal length was the only signs of the DFU developmental toxicity observed in pups exposed to the highest compound dose. Lack of teratogenicity was found in piroxicam and DFU-exposed groups. Prenatal exposure to non-selective COX inhibitors increases the risk of VSD and MD when compared to historic control but not with selective COX-2 inhibitors. CONCLUSION: Both selective and non-selective COX-2 inhibitors were toxic for rats fetuses when administered in the highest dose. Unlike DFU, piroxicam was also highly toxic to the dams. Prenatal exposure to selective COX-2 inhibitors does not increase the risk of ventricular septal and midline defects in rat when compared to non-selective drugs and historic control."],"offsets":[[150,2003]]}],"entities":[{"id":"20124","type":"Disease","text":["toxicity"],"offsets":[[28,36]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"20125","type":"Chemical","text":["DFU"],"offsets":[[125,128]],"normalized":[{"db_name":"MESH","db_id":"C106876"}]},{"id":"20126","type":"Chemical","text":["piroxicam"],"offsets":[[133,142]],"normalized":[{"db_name":"MESH","db_id":"D010894"}]},{"id":"20127","type":"Disease","text":["toxicity"],"offsets":[[268,276]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"20128","type":"Disease","text":["toxicity"],"offsets":[[409,417]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"20129","type":"Chemical","text":["piroxicam"],"offsets":[[440,449]],"normalized":[{"db_name":"MESH","db_id":"D010894"}]},{"id":"20130","type":"Chemical","text":["DFU"],"offsets":[[466,469]],"normalized":[{"db_name":"MESH","db_id":"C106876"}]},{"id":"20131","type":"Chemical","text":["5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl) phenyl-2(5H)-furanon"],"offsets":[[471,545]],"normalized":[{"db_name":"MESH","db_id":"C106876"}]},{"id":"20132","type":"Chemical","text":["piroxicam"],"offsets":[[716,725]],"normalized":[{"db_name":"MESH","db_id":"D010894"}]},{"id":"20133","type":"Chemical","text":["DFU"],"offsets":[[757,760]],"normalized":[{"db_name":"MESH","db_id":"C106876"}]},{"id":"20134","type":"Disease","text":["ventricular septal (VSD) and midline (MD) defects"],"offsets":[[919,968]],"normalized":[{"db_name":"MESH","db_id":"D006345"},{"db_name":"MESH","db_id":"D009436"}]},{"id":"20135","type":"Disease","text":["ventricular septal (VSD)","defects"],"offsets":[[919,943],[961,968]],"normalized":[{"db_name":"MESH","db_id":"D006345"}]},{"id":"20136","type":"Disease","text":["midline (MD) defects"],"offsets":[[946,966]],"normalized":[{"db_name":"MESH","db_id":"D009436"}]},{"id":"20137","type":"Chemical","text":["piroxicam"],"offsets":[[1010,1019]],"normalized":[{"db_name":"MESH","db_id":"D010894"}]},{"id":"20138","type":"Disease","text":["toxicity"],"offsets":[[1119,1127]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"20139","type":"Disease","text":["intrauterine growth retardation"],"offsets":[[1129,1160]],"normalized":[{"db_name":"MESH","db_id":"D005317"}]},{"id":"20140","type":"Disease","text":["increase of external and skeletal variations"],"offsets":[[1166,1210]],"normalized":[{"db_name":"MESH","db_id":"D009139"}]},{"id":"20141","type":"Chemical","text":["piroxicam"],"offsets":[[1263,1272]],"normalized":[{"db_name":"MESH","db_id":"D010894"}]},{"id":"20142","type":"Chemical","text":["DFU"],"offsets":[[1325,1328]],"normalized":[{"db_name":"MESH","db_id":"C106876"}]},{"id":"20143","type":"Disease","text":["toxicity"],"offsets":[[1343,1351]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"20144","type":"Chemical","text":["piroxicam"],"offsets":[[1443,1452]],"normalized":[{"db_name":"MESH","db_id":"D010894"}]},{"id":"20145","type":"Chemical","text":["DFU"],"offsets":[[1457,1460]],"normalized":[{"db_name":"MESH","db_id":"C106876"}]},{"id":"20146","type":"Chemical","text":["DFU"],"offsets":[[1771,1774]],"normalized":[{"db_name":"MESH","db_id":"C106876"}]},{"id":"20147","type":"Chemical","text":["piroxicam"],"offsets":[[1776,1785]],"normalized":[{"db_name":"MESH","db_id":"D010894"}]},{"id":"20148","type":"Disease","text":["ventricular septal and midline defects"],"offsets":[[1899,1937]],"normalized":[{"db_name":"MESH","db_id":"D006345"},{"db_name":"MESH","db_id":"D009436"}]},{"id":"20149","type":"Disease","text":["ventricular septal","defects"],"offsets":[[1899,1917],[1930,1937]],"normalized":[{"db_name":"MESH","db_id":"D006345"}]},{"id":"20150","type":"Disease","text":["midline defects"],"offsets":[[1922,1937]],"normalized":[{"db_name":"MESH","db_id":"D009436"}]}],"events":[],"coreferences":[],"relations":[{"id":"20151","type":"CID","arg1_id":"20126","arg2_id":"20139","normalized":[]},{"id":"20152","type":"CID","arg1_id":"20129","arg2_id":"20139","normalized":[]},{"id":"20153","type":"CID","arg1_id":"20132","arg2_id":"20139","normalized":[]},{"id":"20154","type":"CID","arg1_id":"20137","arg2_id":"20139","normalized":[]},{"id":"20155","type":"CID","arg1_id":"20141","arg2_id":"20139","normalized":[]},{"id":"20156","type":"CID","arg1_id":"20144","arg2_id":"20139","normalized":[]},{"id":"20157","type":"CID","arg1_id":"20147","arg2_id":"20139","normalized":[]},{"id":"20158","type":"CID","arg1_id":"20126","arg2_id":"20140","normalized":[]},{"id":"20159","type":"CID","arg1_id":"20129","arg2_id":"20140","normalized":[]},{"id":"20160","type":"CID","arg1_id":"20132","arg2_id":"20140","normalized":[]},{"id":"20161","type":"CID","arg1_id":"20137","arg2_id":"20140","normalized":[]},{"id":"20162","type":"CID","arg1_id":"20141","arg2_id":"20140","normalized":[]},{"id":"20163","type":"CID","arg1_id":"20144","arg2_id":"20140","normalized":[]},{"id":"20164","type":"CID","arg1_id":"20147","arg2_id":"20140","normalized":[]},{"id":"20165","type":"CID","arg1_id":"20125","arg2_id":"20139","normalized":[]},{"id":"20166","type":"CID","arg1_id":"20130","arg2_id":"20139","normalized":[]},{"id":"20167","type":"CID","arg1_id":"20131","arg2_id":"20139","normalized":[]},{"id":"20168","type":"CID","arg1_id":"20133","arg2_id":"20139","normalized":[]},{"id":"20169","type":"CID","arg1_id":"20142","arg2_id":"20139","normalized":[]},{"id":"20170","type":"CID","arg1_id":"20145","arg2_id":"20139","normalized":[]},{"id":"20171","type":"CID","arg1_id":"20146","arg2_id":"20139","normalized":[]}]}
{"id":"20172","document_id":"12921865","passages":[{"id":"20173","type":"title","text":["Protective efficacy of neuroactive steroids against cocaine kindled-seizures in mice."],"offsets":[[0,85]]},{"id":"20174","type":"abstract","text":["Neuroactive steroids demonstrate pharmacological actions that have relevance for a host of neurological and psychiatric disorders. They offer protection against seizures in a range of models and seem to inhibit certain stages of drug dependence in preclinical assessments. The present study was designed to evaluate two endogenous and one synthetic neuroactive steroid that positively modulate the gamma-aminobutyric acid (GABA(A)) receptor against the increase in sensitivity to the convulsant effects of cocaine engendered by repeated cocaine administration (seizure kindling). Allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one), pregnanolone (3alpha-hydroxy-5beta-pregnan-20-one) and ganaxolone (a synthetic derivative of allopregnanolone 3alpha-hydroxy-3beta-methyl-5alpha-pregnan-20-one) were tested for their ability to suppress the expression (anticonvulsant effect) and development (antiepileptogenic effect) of cocaine-kindled seizures in male, Swiss-Webster mice. Kindled seizures were induced by daily administration of 60 mg\/kg cocaine for 5 days. All of these positive GABA(A) modulators suppressed the expression of kindled seizures, whereas only allopregnanolone and ganaxolone inhibited the development of kindling. Allopregnanolone and pregnanolone, but not ganaxolone, also reduced cumulative lethality associated with kindling. These findings demonstrate that some neuroactive steroids attenuate convulsant and sensitizing properties of cocaine and add to a growing literature on their potential use in the modulation of effects of drugs of abuse."],"offsets":[[86,1657]]}],"entities":[{"id":"20175","type":"Chemical","text":["steroids"],"offsets":[[35,43]],"normalized":[{"db_name":"MESH","db_id":"D013256"}]},{"id":"20176","type":"Chemical","text":["cocaine"],"offsets":[[52,59]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"20177","type":"Disease","text":["seizures"],"offsets":[[68,76]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"20178","type":"Chemical","text":["steroids"],"offsets":[[98,106]],"normalized":[{"db_name":"MESH","db_id":"D013256"}]},{"id":"20179","type":"Disease","text":["neurological and psychiatric disorders"],"offsets":[[177,215]],"normalized":[{"db_name":"MESH","db_id":"D009422"},{"db_name":"MESH","db_id":"D001523"}]},{"id":"20180","type":"Disease","text":["neurological","disorders"],"offsets":[[177,189],[206,215]],"normalized":[{"db_name":"MESH","db_id":"D009422"}]},{"id":"20181","type":"Disease","text":["psychiatric disorders"],"offsets":[[194,215]],"normalized":[{"db_name":"MESH","db_id":"D001523"}]},{"id":"20182","type":"Disease","text":["seizures"],"offsets":[[247,255]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"20183","type":"Disease","text":["drug dependence"],"offsets":[[315,330]],"normalized":[{"db_name":"MESH","db_id":"D019966"}]},{"id":"20184","type":"Chemical","text":["steroid"],"offsets":[[447,454]],"normalized":[{"db_name":"MESH","db_id":"D013256"}]},{"id":"20185","type":"Chemical","text":["gamma-aminobutyric acid"],"offsets":[[484,507]],"normalized":[{"db_name":"MESH","db_id":"D005680"}]},{"id":"20186","type":"Chemical","text":["GABA"],"offsets":[[509,513]],"normalized":[{"db_name":"MESH","db_id":"D005680"}]},{"id":"20187","type":"Chemical","text":["cocaine"],"offsets":[[592,599]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"20188","type":"Chemical","text":["cocaine"],"offsets":[[623,630]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"20189","type":"Disease","text":["seizure"],"offsets":[[647,654]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"20190","type":"Chemical","text":["Allopregnanolone"],"offsets":[[666,682]],"normalized":[{"db_name":"MESH","db_id":"D011280"}]},{"id":"20191","type":"Chemical","text":["3alpha-hydroxy-5alpha-pregnan-20-one"],"offsets":[[684,720]],"normalized":[{"db_name":"MESH","db_id":"D011280"}]},{"id":"20192","type":"Chemical","text":["pregnanolone"],"offsets":[[723,735]],"normalized":[{"db_name":"MESH","db_id":"D011280"}]},{"id":"20193","type":"Chemical","text":["3alpha-hydroxy-5beta-pregnan-20-one"],"offsets":[[737,772]],"normalized":[{"db_name":"MESH","db_id":"D011280"}]},{"id":"20194","type":"Chemical","text":["ganaxolone"],"offsets":[[778,788]],"normalized":[{"db_name":"MESH","db_id":"C105051"}]},{"id":"20195","type":"Chemical","text":["allopregnanolone"],"offsets":[[816,832]],"normalized":[{"db_name":"MESH","db_id":"D011280"}]},{"id":"20196","type":"Chemical","text":["3alpha-hydroxy-3beta-methyl-5alpha-pregnan-20-one"],"offsets":[[833,882]],"normalized":[{"db_name":"MESH","db_id":"C105051"}]},{"id":"20197","type":"Chemical","text":["cocaine"],"offsets":[[1011,1018]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"20198","type":"Disease","text":["seizures"],"offsets":[[1027,1035]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"20199","type":"Disease","text":["seizures"],"offsets":[[1073,1081]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"20200","type":"Chemical","text":["cocaine"],"offsets":[[1131,1138]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"20201","type":"Chemical","text":["GABA"],"offsets":[[1173,1177]],"normalized":[{"db_name":"MESH","db_id":"D005680"}]},{"id":"20202","type":"Disease","text":["seizures"],"offsets":[[1229,1237]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"20203","type":"Chemical","text":["allopregnanolone"],"offsets":[[1252,1268]],"normalized":[{"db_name":"MESH","db_id":"D011280"}]},{"id":"20204","type":"Chemical","text":["ganaxolone"],"offsets":[[1273,1283]],"normalized":[{"db_name":"MESH","db_id":"C105051"}]},{"id":"20205","type":"Chemical","text":["Allopregnanolone"],"offsets":[[1323,1339]],"normalized":[{"db_name":"MESH","db_id":"D011280"}]},{"id":"20206","type":"Chemical","text":["pregnanolone"],"offsets":[[1344,1356]],"normalized":[{"db_name":"MESH","db_id":"D011280"}]},{"id":"20207","type":"Chemical","text":["ganaxolone"],"offsets":[[1366,1376]],"normalized":[{"db_name":"MESH","db_id":"C105051"}]},{"id":"20208","type":"Chemical","text":["steroids"],"offsets":[[1487,1495]],"normalized":[{"db_name":"MESH","db_id":"D013256"}]},{"id":"20209","type":"Chemical","text":["cocaine"],"offsets":[[1547,1554]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]}],"events":[],"coreferences":[],"relations":[{"id":"20210","type":"CID","arg1_id":"20176","arg2_id":"20177","normalized":[]},{"id":"20211","type":"CID","arg1_id":"20176","arg2_id":"20182","normalized":[]},{"id":"20212","type":"CID","arg1_id":"20176","arg2_id":"20189","normalized":[]},{"id":"20213","type":"CID","arg1_id":"20176","arg2_id":"20198","normalized":[]},{"id":"20214","type":"CID","arg1_id":"20176","arg2_id":"20199","normalized":[]},{"id":"20215","type":"CID","arg1_id":"20176","arg2_id":"20202","normalized":[]},{"id":"20216","type":"CID","arg1_id":"20187","arg2_id":"20177","normalized":[]},{"id":"20217","type":"CID","arg1_id":"20187","arg2_id":"20182","normalized":[]},{"id":"20218","type":"CID","arg1_id":"20187","arg2_id":"20189","normalized":[]},{"id":"20219","type":"CID","arg1_id":"20187","arg2_id":"20198","normalized":[]},{"id":"20220","type":"CID","arg1_id":"20187","arg2_id":"20199","normalized":[]},{"id":"20221","type":"CID","arg1_id":"20187","arg2_id":"20202","normalized":[]},{"id":"20222","type":"CID","arg1_id":"20188","arg2_id":"20177","normalized":[]},{"id":"20223","type":"CID","arg1_id":"20188","arg2_id":"20182","normalized":[]},{"id":"20224","type":"CID","arg1_id":"20188","arg2_id":"20189","normalized":[]},{"id":"20225","type":"CID","arg1_id":"20188","arg2_id":"20198","normalized":[]},{"id":"20226","type":"CID","arg1_id":"20188","arg2_id":"20199","normalized":[]},{"id":"20227","type":"CID","arg1_id":"20188","arg2_id":"20202","normalized":[]},{"id":"20228","type":"CID","arg1_id":"20197","arg2_id":"20177","normalized":[]},{"id":"20229","type":"CID","arg1_id":"20197","arg2_id":"20182","normalized":[]},{"id":"20230","type":"CID","arg1_id":"20197","arg2_id":"20189","normalized":[]},{"id":"20231","type":"CID","arg1_id":"20197","arg2_id":"20198","normalized":[]},{"id":"20232","type":"CID","arg1_id":"20197","arg2_id":"20199","normalized":[]},{"id":"20233","type":"CID","arg1_id":"20197","arg2_id":"20202","normalized":[]},{"id":"20234","type":"CID","arg1_id":"20200","arg2_id":"20177","normalized":[]},{"id":"20235","type":"CID","arg1_id":"20200","arg2_id":"20182","normalized":[]},{"id":"20236","type":"CID","arg1_id":"20200","arg2_id":"20189","normalized":[]},{"id":"20237","type":"CID","arg1_id":"20200","arg2_id":"20198","normalized":[]},{"id":"20238","type":"CID","arg1_id":"20200","arg2_id":"20199","normalized":[]},{"id":"20239","type":"CID","arg1_id":"20200","arg2_id":"20202","normalized":[]},{"id":"20240","type":"CID","arg1_id":"20209","arg2_id":"20177","normalized":[]},{"id":"20241","type":"CID","arg1_id":"20209","arg2_id":"20182","normalized":[]},{"id":"20242","type":"CID","arg1_id":"20209","arg2_id":"20189","normalized":[]},{"id":"20243","type":"CID","arg1_id":"20209","arg2_id":"20198","normalized":[]},{"id":"20244","type":"CID","arg1_id":"20209","arg2_id":"20199","normalized":[]},{"id":"20245","type":"CID","arg1_id":"20209","arg2_id":"20202","normalized":[]}]}
{"id":"20246","document_id":"12584269","passages":[{"id":"20247","type":"title","text":["Kidney function and morphology after short-term combination therapy with cyclosporine A, tacrolimus and sirolimus in the rat."],"offsets":[[0,125]]},{"id":"20248","type":"abstract","text":["BACKGROUND: Sirolimus (SRL) may supplement calcineurin inhibitors in clinical organ transplantation. These are nephrotoxic, but SRL seems to act differently displaying only minor nephrotoxic effects, although this question is still open. In a number of treatment protocols where SRL was combined with a calcineurin inhibitor indications of a synergistic nephrotoxic effect were described. The aim of this study was to examine further the renal function, including morphological analysis of the kidneys of male Sprague-Dawley rats treated with either cyclosporine A (CsA), tacrolimus (FK506) or SRL as monotherapies or in different combinations. METHODS: For a period of 2 weeks, CsA 15 mg\/kg\/day (given orally), FK506 3.0 mg\/kg\/day (given orally) or SRL 0.4 mg\/kg\/day (given intraperitoneally) was administered once a day as these doses have earlier been found to achieve a significant immunosuppressive effect in Sprague-Dawley rats. In the 'conscious catheterized rat' model, the glomerular filtration rate (GFR) was measured as the clearance of Cr(EDTA). The morphological analysis of the kidneys included a semi-quantitative scoring system analysing the degree of striped fibrosis, subcapsular fibrosis and the number of basophilic tubules, plus an additional stereological analysis of the total grade of fibrosis in the cortex stained with Sirius Red. RESULTS: CsA, FK506 and SRL all significantly decreased the GFR. A further deterioration was seen when CsA was combined with either FK506 or SRL, whereas the GFR remained unchanged in the group treated with FK506 plus SRL when compared with treatment with any of the single substances. The morphological changes presented a similar pattern. The semi-quantitative scoring was significantly worst in the group treated with CsA plus SRL (P<0.001 compared with controls) and the analysis of the total grade of fibrosis also showed the highest proportion in the same group and was significantly different from controls (P<0.02). The FK506 plus SRL combination showed only a marginally higher degree of fibrosis as compared with controls (P=0.05). CONCLUSION: This rat study demonstrated a synergistic nephrotoxic effect of CsA plus SRL, whereas FK506 plus SRL was better tolerated."],"offsets":[[126,2359]]}],"entities":[{"id":"20249","type":"Chemical","text":["cyclosporine A"],"offsets":[[73,87]],"normalized":[{"db_name":"MESH","db_id":"D016572"}]},{"id":"20250","type":"Chemical","text":["tacrolimus"],"offsets":[[89,99]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"20251","type":"Chemical","text":["sirolimus"],"offsets":[[104,113]],"normalized":[{"db_name":"MESH","db_id":"D020123"}]},{"id":"20252","type":"Chemical","text":["Sirolimus"],"offsets":[[138,147]],"normalized":[{"db_name":"MESH","db_id":"D020123"}]},{"id":"20253","type":"Chemical","text":["SRL"],"offsets":[[149,152]],"normalized":[{"db_name":"MESH","db_id":"D020123"}]},{"id":"20254","type":"Disease","text":["nephrotoxic"],"offsets":[[237,248]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"20255","type":"Chemical","text":["SRL"],"offsets":[[254,257]],"normalized":[{"db_name":"MESH","db_id":"D020123"}]},{"id":"20256","type":"Disease","text":["nephrotoxic"],"offsets":[[305,316]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"20257","type":"Chemical","text":["SRL"],"offsets":[[405,408]],"normalized":[{"db_name":"MESH","db_id":"D020123"}]},{"id":"20258","type":"Disease","text":["nephrotoxic"],"offsets":[[480,491]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"20259","type":"Chemical","text":["cyclosporine 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{"id":"20413","document_id":"10406016","passages":[{"id":"20414","type":"title","text":["Effect of fucoidan treatment on collagenase-induced intracerebral hemorrhage in rats."],"offsets":[[0,85]]},{"id":"20415","type":"abstract","text":["Inflammatory cells are postulated to mediate some of the brain damage following ischemic stroke. Intracerebral hemorrhage is associated with more inflammation than ischemic stroke. We tested the sulfated polysaccharide fucoidan, which has been reported to reduce inflammatory brain damage, in a rat model of intracerebral hemorrhage induced by injection of bacterial collagenase into the caudate nucleus. Rats were treated with seven day intravenous infusion of fucoidan (30 micrograms h-1) or vehicle. The hematoma was assessed in vivo by magnetic resonance imaging. Motor behavior, passive avoidance, and skilled forelimb function were tested repeatedly for six weeks. Fucoidan-treated rats exhibited evidence of impaired blood clotting and hemodilution, had larger hematomas, and tended to have less inflammation in the vicinity of the hematoma after three days. They showed significantly more rapid improvement of motor function in the first week following hemorrhage and better memory retention in the passive avoidance test. Acute white matter edema and eventual neuronal loss in the striatum adjacent to the hematoma did not differ between the two groups. Investigation of more specific anti-inflammatory agents and hemodiluting agents are warranted in intracerebral hemorrhage."],"offsets":[[86,1371]]}],"entities":[{"id":"20416","type":"Chemical","text":["fucoidan"],"offsets":[[10,18]],"normalized":[{"db_name":"MESH","db_id":"C007789"}]},{"id":"20417","type":"Disease","text":["intracerebral hemorrhage"],"offsets":[[52,76]],"normalized":[{"db_name":"MESH","db_id":"D002543"}]},{"id":"20418","type":"Disease","text":["brain damage"],"offsets":[[143,155]],"normalized":[{"db_name":"MESH","db_id":"D001925"}]},{"id":"20419","type":"Disease","text":["ischemic stroke"],"offsets":[[166,181]],"normalized":[{"db_name":"MESH","db_id":"D002544"}]},{"id":"20420","type":"Disease","text":["Intracerebral hemorrhage"],"offsets":[[183,207]],"normalized":[{"db_name":"MESH","db_id":"D002543"}]},{"id":"20421","type":"Disease","text":["inflammation"],"offsets":[[232,244]],"normalized":[{"db_name":"MESH","db_id":"D007249"}]},{"id":"20422","type":"Disease","text":["ischemic stroke"],"offsets":[[250,265]],"normalized":[{"db_name":"MESH","db_id":"D002544"}]},{"id":"20423","type":"Chemical","text":["fucoidan"],"offsets":[[305,313]],"normalized":[{"db_name":"MESH","db_id":"C007789"}]},{"id":"20424","type":"Disease","text":["brain damage"],"offsets":[[362,374]],"normalized":[{"db_name":"MESH","db_id":"D001925"}]},{"id":"20425","type":"Disease","text":["intracerebral hemorrhage"],"offsets":[[394,418]],"normalized":[{"db_name":"MESH","db_id":"D002543"}]},{"id":"20426","type":"Chemical","text":["fucoidan"],"offsets":[[548,556]],"normalized":[{"db_name":"MESH","db_id":"C007789"}]},{"id":"20427","type":"Disease","text":["hematoma"],"offsets":[[593,601]],"normalized":[{"db_name":"MESH","db_id":"D006406"}]},{"id":"20428","type":"Chemical","text":["Fucoidan"],"offsets":[[757,765]],"normalized":[{"db_name":"MESH","db_id":"C007789"}]},{"id":"20429","type":"Disease","text":["impaired blood clotting"],"offsets":[[801,824]],"normalized":[{"db_name":"MESH","db_id":"D020141"}]},{"id":"20430","type":"Disease","text":["hemodilution"],"offsets":[[829,841]],"normalized":[{"db_name":"MESH","db_id":"D020141"}]},{"id":"20431","type":"Disease","text":["hematomas"],"offsets":[[854,863]],"normalized":[{"db_name":"MESH","db_id":"D006406"}]},{"id":"20432","type":"Disease","text":["inflammation"],"offsets":[[889,901]],"normalized":[{"db_name":"MESH","db_id":"D007249"}]},{"id":"20433","type":"Disease","text":["hematoma"],"offsets":[[925,933]],"normalized":[{"db_name":"MESH","db_id":"D006406"}]},{"id":"20434","type":"Disease","text":["hemorrhage"],"offsets":[[1047,1057]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"20435","type":"Disease","text":["white matter edema"],"offsets":[[1123,1141]],"normalized":[{"db_name":"MESH","db_id":"D001929"}]},{"id":"20436","type":"Disease","text":["neuronal loss"],"offsets":[[1155,1168]],"normalized":[{"db_name":"MESH","db_id":"D009410"}]},{"id":"20437","type":"Disease","text":["hematoma"],"offsets":[[1201,1209]],"normalized":[{"db_name":"MESH","db_id":"D006406"}]},{"id":"20438","type":"Disease","text":["intracerebral hemorrhage"],"offsets":[[1346,1370]],"normalized":[{"db_name":"MESH","db_id":"D002543"}]}],"events":[],"coreferences":[],"relations":[{"id":"20439","type":"CID","arg1_id":"20416","arg2_id":"20429","normalized":[]},{"id":"20440","type":"CID","arg1_id":"20416","arg2_id":"20430","normalized":[]},{"id":"20441","type":"CID","arg1_id":"20423","arg2_id":"20429","normalized":[]},{"id":"20442","type":"CID","arg1_id":"20423","arg2_id":"20430","normalized":[]},{"id":"20443","type":"CID","arg1_id":"20426","arg2_id":"20429","normalized":[]},{"id":"20444","type":"CID","arg1_id":"20426","arg2_id":"20430","normalized":[]},{"id":"20445","type":"CID","arg1_id":"20428","arg2_id":"20429","normalized":[]},{"id":"20446","type":"CID","arg1_id":"20428","arg2_id":"20430","normalized":[]},{"id":"20447","type":"CID","arg1_id":"20416","arg2_id":"20435","normalized":[]},{"id":"20448","type":"CID","arg1_id":"20423","arg2_id":"20435","normalized":[]},{"id":"20449","type":"CID","arg1_id":"20426","arg2_id":"20435","normalized":[]},{"id":"20450","type":"CID","arg1_id":"20428","arg2_id":"20435","normalized":[]}]}
{"id":"20451","document_id":"3403780","passages":[{"id":"20452","type":"title","text":["Paracetamol-associated coma, metabolic acidosis, renal and hepatic failure."],"offsets":[[0,75]]},{"id":"20453","type":"abstract","text":["A case of metabolic acidosis, acute renal failure and hepatic failure following paracetamol ingestion is presented. The diagnostic difficulty at presentation is highlighted. Continuous arteriovenous haemofiltration proved a valuable means of maintaining fluid and electrolyte balance. The patient recovered."],"offsets":[[76,383]]}],"entities":[{"id":"20454","type":"Chemical","text":["Paracetamol"],"offsets":[[0,11]],"normalized":[{"db_name":"MESH","db_id":"D000082"}]},{"id":"20455","type":"Disease","text":["coma"],"offsets":[[23,27]],"normalized":[{"db_name":"MESH","db_id":"D003128"}]},{"id":"20456","type":"Disease","text":["metabolic acidosis"],"offsets":[[29,47]],"normalized":[{"db_name":"MESH","db_id":"D000138"}]},{"id":"20457","type":"Disease","text":["renal and hepatic failure"],"offsets":[[49,74]],"normalized":[{"db_name":"MESH","db_id":"D058186"},{"db_name":"MESH","db_id":"D017093"}]},{"id":"20458","type":"Disease","text":["renal","failure"],"offsets":[[49,54],[67,74]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"20459","type":"Disease","text":["hepatic failure"],"offsets":[[59,74]],"normalized":[{"db_name":"MESH","db_id":"D017093"}]},{"id":"20460","type":"Disease","text":["metabolic acidosis"],"offsets":[[86,104]],"normalized":[{"db_name":"MESH","db_id":"D000138"}]},{"id":"20461","type":"Disease","text":["acute renal failure and hepatic failure"],"offsets":[[106,145]],"normalized":[{"db_name":"MESH","db_id":"D058186"},{"db_name":"MESH","db_id":"D017114"}]},{"id":"20462","type":"Disease","text":["acute renal failure"],"offsets":[[106,125]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"20463","type":"Disease","text":["acute","hepatic failure"],"offsets":[[106,111],[130,145]],"normalized":[{"db_name":"MESH","db_id":"D017114"}]},{"id":"20464","type":"Chemical","text":["paracetamol"],"offsets":[[156,167]],"normalized":[{"db_name":"MESH","db_id":"D000082"}]}],"events":[],"coreferences":[],"relations":[{"id":"20465","type":"CID","arg1_id":"20454","arg2_id":"20456","normalized":[]},{"id":"20466","type":"CID","arg1_id":"20454","arg2_id":"20460","normalized":[]},{"id":"20467","type":"CID","arg1_id":"20464","arg2_id":"20456","normalized":[]},{"id":"20468","type":"CID","arg1_id":"20464","arg2_id":"20460","normalized":[]},{"id":"20469","type":"CID","arg1_id":"20454","arg2_id":"20461","normalized":[]},{"id":"20470","type":"CID","arg1_id":"20454","arg2_id":"20463","normalized":[]},{"id":"20471","type":"CID","arg1_id":"20464","arg2_id":"20461","normalized":[]},{"id":"20472","type":"CID","arg1_id":"20464","arg2_id":"20463","normalized":[]},{"id":"20473","type":"CID","arg1_id":"20454","arg2_id":"20457","normalized":[]},{"id":"20474","type":"CID","arg1_id":"20454","arg2_id":"20458","normalized":[]},{"id":"20475","type":"CID","arg1_id":"20454","arg2_id":"20461","normalized":[]},{"id":"20476","type":"CID","arg1_id":"20454","arg2_id":"20462","normalized":[]},{"id":"20477","type":"CID","arg1_id":"20464","arg2_id":"20457","normalized":[]},{"id":"20478","type":"CID","arg1_id":"20464","arg2_id":"20458","normalized":[]},{"id":"20479","type":"CID","arg1_id":"20464","arg2_id":"20461","normalized":[]},{"id":"20480","type":"CID","arg1_id":"20464","arg2_id":"20462","normalized":[]}]}
{"id":"20481","document_id":"3101906","passages":[{"id":"20482","type":"title","text":["Hepatic reactions associated with ketoconazole in the United Kingdom."],"offsets":[[0,69]]},{"id":"20483","type":"abstract","text":["Ketoconazole was introduced in the United Kingdom in 1981. By November 1984 the Committee on Safety of Medicines had received 82 reports of possible hepatotoxicity associated with the drug, including five deaths. An analysis of the 75 cases that had been adequately followed up suggested that 16, including three deaths, were probably related to treatment with the drug. Of the remainder, 48 were possibly related to treatment, five were unlikely to be so, and six were unclassifiable. The mean age of patients in the 16 probable cases was 57.9, with hepatotoxicity being more common in women. The average duration of treatment before the onset of jaundice was 61 days. None of these well validated cases occurred within the first 10 days after treatment. The results of serum liver function tests suggested hepatocellular injury in 10 (63%); the rest showed a mixed pattern. In contrast, the results of histological examination of the liver often showed evidence of cholestasis. The characteristics of the 48 patients in the possible cases were similar. Allergic manifestations such as rash and eosinophilia were rare. Hepatitis was usually reversible when treatment was stopped, with the results of liver function tests returning to normal after an average of 3.1 months. In two of the three deaths probably associated with ketoconazole treatment the drug had been continued after the onset of jaundice and other symptoms of hepatitis. Clinical and biochemical monitoring at regular intervals for evidence of hepatitis is advised during long term treatment with ketoconazole to prevent possible serious hepatic injury."],"offsets":[[70,1690]]}],"entities":[{"id":"20484","type":"Chemical","text":["ketoconazole"],"offsets":[[34,46]],"normalized":[{"db_name":"MESH","db_id":"D007654"}]},{"id":"20485","type":"Chemical","text":["Ketoconazole"],"offsets":[[70,82]],"normalized":[{"db_name":"MESH","db_id":"D007654"}]},{"id":"20486","type":"Disease","text":["hepatotoxicity"],"offsets":[[219,233]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"20487","type":"Disease","text":["deaths"],"offsets":[[275,281]],"normalized":[{"db_name":"MESH","db_id":"D003643"}]},{"id":"20488","type":"Disease","text":["deaths"],"offsets":[[383,389]],"normalized":[{"db_name":"MESH","db_id":"D003643"}]},{"id":"20489","type":"Disease","text":["hepatotoxicity"],"offsets":[[621,635]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"20490","type":"Disease","text":["jaundice"],"offsets":[[718,726]],"normalized":[{"db_name":"MESH","db_id":"D007565"}]},{"id":"20491","type":"Disease","text":["hepatocellular injury"],"offsets":[[878,899]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"20492","type":"Disease","text":["cholestasis"],"offsets":[[1037,1048]],"normalized":[{"db_name":"MESH","db_id":"D002779"}]},{"id":"20493","type":"Disease","text":["rash"],"offsets":[[1157,1161]],"normalized":[{"db_name":"MESH","db_id":"D005076"}]},{"id":"20494","type":"Disease","text":["eosinophilia"],"offsets":[[1166,1178]],"normalized":[{"db_name":"MESH","db_id":"D004802"}]},{"id":"20495","type":"Disease","text":["Hepatitis"],"offsets":[[1190,1199]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"20496","type":"Disease","text":["deaths"],"offsets":[[1364,1370]],"normalized":[{"db_name":"MESH","db_id":"D003643"}]},{"id":"20497","type":"Chemical","text":["ketoconazole"],"offsets":[[1396,1408]],"normalized":[{"db_name":"MESH","db_id":"D007654"}]},{"id":"20498","type":"Disease","text":["jaundice"],"offsets":[[1466,1474]],"normalized":[{"db_name":"MESH","db_id":"D007565"}]},{"id":"20499","type":"Disease","text":["hepatitis"],"offsets":[[1497,1506]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"20500","type":"Disease","text":["hepatitis"],"offsets":[[1581,1590]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"20501","type":"Chemical","text":["ketoconazole"],"offsets":[[1634,1646]],"normalized":[{"db_name":"MESH","db_id":"D007654"}]},{"id":"20502","type":"Disease","text":["hepatic 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{"id":"20543","document_id":"9088814","passages":[{"id":"20544","type":"title","text":["Combined effects of prolonged prostaglandin E1-induced hypotension and haemodilution on human hepatic function."],"offsets":[[0,111]]},{"id":"20545","type":"abstract","text":["Combined effects of prolonged prostaglandin E1 (PGE1)-induced hypotension and haemodilution on hepatic function were studied in 30 patients undergoing hip surgery. The patients were randomly allocated to one of three groups; those in group A (n = 10) were subjected to controlled hypotension alone, those in group B (n = 10) to haemodilution alone and those in group C (n = 10) to both controlled hypotension and haemodilution. Haemodilution in groups B and C was produced by withdrawing approximately 1000 mL of blood and replacing it with the same amount of dextran solution, and final haematocrit values were 21 or 22%. Controlled hypotension in groups A and C was induced with PGE1 to maintain mean arterial blood pressure at 55 mmHg for 180 min. Measurements included arterial ketone body ratio (AKBR, aceto-acetate\/3-hydroxybutyrate) and clinical hepatic function parameters. AKBR and biological hepatic function tests showed no change throughout the time course in groups A and B. In group C, AKBR showed a significant decrease at 120 min (-40%) and at 180 min (-49%) after the start of hypotension and at 60 min (-32%) after recovery of normotension, and SGOT, SGPT, LDH and total bilirubin showed significant increases after operation. The results suggest that a prolonged combination of more than 120 min of PGE1-induced hypotension and moderate haemodilution would cause impairment of hepatic function."],"offsets":[[112,1525]]}],"entities":[{"id":"20546","type":"Chemical","text":["prostaglandin E1"],"offsets":[[30,46]],"normalized":[{"db_name":"MESH","db_id":"D000527"}]},{"id":"20547","type":"Disease","text":["hypotension"],"offsets":[[55,66]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"20548","type":"Disease","text":["haemodilution"],"offsets":[[71,84]],"normalized":[{"db_name":"MESH","db_id":"D020141"}]},{"id":"20549","type":"Chemical","text":["prostaglandin 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{"id":"20609","document_id":"20880751","passages":[{"id":"20610","type":"title","text":["Levodopa-induced dyskinesias in patients with Parkinson's disease: filling the bench-to-bedside gap."],"offsets":[[0,100]]},{"id":"20611","type":"abstract","text":["Levodopa is the most effective drug for the treatment of Parkinson's disease. However, the long-term use of this dopamine precursor is complicated by highly disabling fluctuations and dyskinesias. Although preclinical and clinical findings suggest pulsatile stimulation of striatal postsynaptic receptors as a key mechanism underlying levodopa-induced dyskinesias, their pathogenesis is still unclear. In recent years, evidence from animal models of Parkinson's disease has provided important information to understand the effect of specific receptor and post-receptor molecular mechanisms underlying the development of dyskinetic movements. Recent preclinical and clinical data from promising lines of research focus on the differential role of presynaptic versus postsynaptic mechanisms, dopamine receptor subtypes, ionotropic and metabotropic glutamate receptors, and non-dopaminergic neurotransmitter systems in the pathophysiology of levodopa-induced dyskinesias."],"offsets":[[101,1069]]}],"entities":[{"id":"20612","type":"Chemical","text":["Levodopa"],"offsets":[[0,8]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"20613","type":"Disease","text":["dyskinesias"],"offsets":[[17,28]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"20614","type":"Disease","text":["Parkinson's disease"],"offsets":[[46,65]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"20615","type":"Chemical","text":["Levodopa"],"offsets":[[101,109]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"20616","type":"Disease","text":["Parkinson's disease"],"offsets":[[158,177]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"20617","type":"Chemical","text":["dopamine"],"offsets":[[214,222]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"20618","type":"Disease","text":["dyskinesias"],"offsets":[[285,296]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"20619","type":"Chemical","text":["levodopa"],"offsets":[[436,444]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"20620","type":"Disease","text":["dyskinesias"],"offsets":[[453,464]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"20621","type":"Disease","text":["Parkinson's disease"],"offsets":[[551,570]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"20622","type":"Disease","text":["dyskinetic movements"],"offsets":[[721,741]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"20623","type":"Chemical","text":["dopamine"],"offsets":[[891,899]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"20624","type":"Chemical","text":["glutamate"],"offsets":[[947,956]],"normalized":[{"db_name":"MESH","db_id":"D018698"}]},{"id":"20625","type":"Chemical","text":["levodopa"],"offsets":[[1040,1048]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"20626","type":"Disease","text":["dyskinesias"],"offsets":[[1057,1068]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]}],"events":[],"coreferences":[],"relations":[{"id":"20627","type":"CID","arg1_id":"20612","arg2_id":"20613","normalized":[]},{"id":"20628","type":"CID","arg1_id":"20612","arg2_id":"20618","normalized":[]},{"id":"20629","type":"CID","arg1_id":"20612","arg2_id":"20620","normalized":[]},{"id":"20630","type":"CID","arg1_id":"20612","arg2_id":"20622","normalized":[]},{"id":"20631","type":"CID","arg1_id":"20612","arg2_id":"20626","normalized":[]},{"id":"20632","type":"CID","arg1_id":"20615","arg2_id":"20613","normalized":[]},{"id":"20633","type":"CID","arg1_id":"20615","arg2_id":"20618","normalized":[]},{"id":"20634","type":"CID","arg1_id":"20615","arg2_id":"20620","normalized":[]},{"id":"20635","type":"CID","arg1_id":"20615","arg2_id":"20622","normalized":[]},{"id":"20636","type":"CID","arg1_id":"20615","arg2_id":"20626","normalized":[]},{"id":"20637","type":"CID","arg1_id":"20619","arg2_id":"20613","normalized":[]},{"id":"20638","type":"CID","arg1_id":"20619","arg2_id":"20618","normalized":[]},{"id":"20639","type":"CID","arg1_id":"20619","arg2_id":"20620","normalized":[]},{"id":"20640","type":"CID","arg1_id":"20619","arg2_id":"20622","normalized":[]},{"id":"20641","type":"CID","arg1_id":"20619","arg2_id":"20626","normalized":[]},{"id":"20642","type":"CID","arg1_id":"20625","arg2_id":"20613","normalized":[]},{"id":"20643","type":"CID","arg1_id":"20625","arg2_id":"20618","normalized":[]},{"id":"20644","type":"CID","arg1_id":"20625","arg2_id":"20620","normalized":[]},{"id":"20645","type":"CID","arg1_id":"20625","arg2_id":"20622","normalized":[]},{"id":"20646","type":"CID","arg1_id":"20625","arg2_id":"20626","normalized":[]}]}
{"id":"20647","document_id":"20080419","passages":[{"id":"20648","type":"title","text":["Prevention of seizures and reorganization of hippocampal functions by transplantation of bone marrow cells in the acute phase of experimental epilepsy."],"offsets":[[0,151]]},{"id":"20649","type":"abstract","text":["In this study, we investigated the therapeutic potential of bone marrow mononuclear cells (BMCs) in a model of epilepsy induced by pilocarpine in rats. BMCs obtained from green fluorescent protein (GFP) transgenic mice or rats were transplanted intravenously after induction of status epilepticus (SE). Spontaneous recurrent seizures (SRS) were monitored using Racine's seizure severity scale. All of the rats in the saline-treated epileptic control group developed SRS, whereas none of the BMC-treated epileptic animals had seizures in the short term (15 days after transplantation), regardless of the BMC source. Over the long-term chronic phase (120 days after transplantation), only 25% of BMC-treated epileptic animals had seizures, but with a lower frequency and duration compared to the epileptic control group. The density of hippocampal neurons in the brains of animals treated with BMCs was markedly preserved. At hippocampal Schaeffer collateral-CA1 synapses, long-term potentiation was preserved in BMC-transplanted rats compared to epileptic controls. The donor-derived GFP(+) cells were rarely found in the brains of transplanted epileptic rats. In conclusion, treatment with BMCs can prevent the development of chronic seizures, reduce neuronal loss, and influence the reorganization of the hippocampal neuronal network."],"offsets":[[152,1487]]}],"entities":[{"id":"20650","type":"Disease","text":["seizures"],"offsets":[[14,22]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"20651","type":"Disease","text":["epilepsy"],"offsets":[[142,150]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"20652","type":"Disease","text":["epilepsy"],"offsets":[[263,271]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"20653","type":"Chemical","text":["pilocarpine"],"offsets":[[283,294]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"20654","type":"Disease","text":["status epilepticus"],"offsets":[[430,448]],"normalized":[{"db_name":"MESH","db_id":"D013226"}]},{"id":"20655","type":"Disease","text":["SE"],"offsets":[[450,452]],"normalized":[{"db_name":"MESH","db_id":"D013226"}]},{"id":"20656","type":"Disease","text":["Spontaneous recurrent seizures"],"offsets":[[455,485]],"normalized":[]},{"id":"20657","type":"Disease","text":["SRS"],"offsets":[[487,490]],"normalized":[]},{"id":"20658","type":"Disease","text":["seizure"],"offsets":[[522,529]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"20659","type":"Disease","text":["epileptic"],"offsets":[[584,593]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"20660","type":"Disease","text":["SRS"],"offsets":[[618,621]],"normalized":[]},{"id":"20661","type":"Disease","text":["epileptic"],"offsets":[[655,664]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"20662","type":"Disease","text":["seizures"],"offsets":[[677,685]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"20663","type":"Disease","text":["epileptic"],"offsets":[[858,867]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"20664","type":"Disease","text":["seizures"],"offsets":[[880,888]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"20665","type":"Disease","text":["epileptic"],"offsets":[[946,955]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"20666","type":"Disease","text":["epileptic"],"offsets":[[1197,1206]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"20667","type":"Disease","text":["epileptic"],"offsets":[[1296,1305]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"20668","type":"Disease","text":["seizures"],"offsets":[[1386,1394]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"20669","type":"Disease","text":["neuronal loss"],"offsets":[[1403,1416]],"normalized":[{"db_name":"MESH","db_id":"D009410"}]}],"events":[],"coreferences":[],"relations":[{"id":"20670","type":"CID","arg1_id":"20653","arg2_id":"20651","normalized":[]},{"id":"20671","type":"CID","arg1_id":"20653","arg2_id":"20652","normalized":[]},{"id":"20672","type":"CID","arg1_id":"20653","arg2_id":"20659","normalized":[]},{"id":"20673","type":"CID","arg1_id":"20653","arg2_id":"20661","normalized":[]},{"id":"20674","type":"CID","arg1_id":"20653","arg2_id":"20663","normalized":[]},{"id":"20675","type":"CID","arg1_id":"20653","arg2_id":"20665","normalized":[]},{"id":"20676","type":"CID","arg1_id":"20653","arg2_id":"20666","normalized":[]},{"id":"20677","type":"CID","arg1_id":"20653","arg2_id":"20667","normalized":[]},{"id":"20678","type":"CID","arg1_id":"20653","arg2_id":"20654","normalized":[]},{"id":"20679","type":"CID","arg1_id":"20653","arg2_id":"20655","normalized":[]}]}
{"id":"20680","document_id":"19445921","passages":[{"id":"20681","type":"title","text":["Cardioprotective effect of salvianolic acid A on isoproterenol-induced myocardial infarction in rats."],"offsets":[[0,101]]},{"id":"20682","type":"abstract","text":["The present study was designed to evaluate the cardioprotective potential of salvianolic acid A on isoproterenol-induced myocardial infarction in rats. Hemodynamic parameters and lead II electrocardiograph were monitored and recorded continuously. Cardiac marker enzymes and antioxidative parameters in serum and heart tissues were measured. Assay for mitochondrial respiratory function and histopathological examination of heart tissues were performed. Isoproterenol-treated rats showed significant increases in the levels of lactate dehydrogenase, aspartate transaminase, creatine kinase and malondialdehyde and significant decreases in the activities of superoxide dismutase, catalase and glutathione peroxidase in serum and heart. These rats also showed declines in left ventricular systolic pressure, maximum and minimum rate of developed left ventricular pressure, and elevation of left ventricular end-diastolic pressure and ST-segment. In addition, mitochondrial respiratory dysfunction characterized by decreased respiratory control ratio and ADP\/O was observed in isoproterenol-treated rats. Administration of salvianolic acid A for a period of 8 days significantly attenuated isoproterenol-induced cardiac dysfunction and myocardial injury and improved mitochondrial respiratory function. The protective role of salvianolic acid A against isoproterenol-induced myocardial damage was further confirmed by histopathological examination. The results of our study suggest that salvianolic acid A possessing antioxidant activity has a significant protective effect against isoproterenol-induced myocardial infarction."],"offsets":[[102,1725]]}],"entities":[{"id":"20683","type":"Chemical","text":["salvianolic acid A"],"offsets":[[27,45]],"normalized":[{"db_name":"MESH","db_id":"C066201"}]},{"id":"20684","type":"Chemical","text":["isoproterenol"],"offsets":[[49,62]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"20685","type":"Disease","text":["myocardial infarction"],"offsets":[[71,92]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"20686","type":"Chemical","text":["salvianolic acid A"],"offsets":[[179,197]],"normalized":[{"db_name":"MESH","db_id":"C066201"}]},{"id":"20687","type":"Chemical","text":["isoproterenol"],"offsets":[[201,214]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"20688","type":"Disease","text":["myocardial 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{"id":"20730","document_id":"18439803","passages":[{"id":"20731","type":"title","text":["Acute effects of N-(2-propylpentanoyl)urea on hippocampal amino acid neurotransmitters in pilocarpine-induced seizure in rats."],"offsets":[[0,126]]},{"id":"20732","type":"abstract","text":["The present study aimed to investigate the anticonvulsant activity as well as the effects on the level of hippocampal amino acid neurotransmitters (glutamate, aspartate, glycine and GABA) of N-(2-propylpentanoyl)urea (VPU) in comparison to its parent compound, valproic acid (VPA). VPU was more potent than VPA, exhibiting the median effective dose (ED(50)) of 49 mg\/kg in protecting rats against pilocarpine-induced seizure whereas the corresponding value for VPA was 322 mg\/kg. In vivo microdialysis demonstrated that an intraperitoneal administration of pilocarpine induced a pronounced increment of hippocampal glutamate and aspartate whereas no significant change was observed on the level of glycine and GABA. Pretreatment with either VPU (50 and 100 mg\/kg) or VPA (300 and 600 mg\/kg) completely abolished pilocarpine-evoked increases in extracellular glutamate and aspartate. In addition, a statistically significant reduction was also observed on the level of GABA and glycine but less than a drastic reduction of glutamate and aspartate level. Based on the finding that VPU and VPA could protect the animals against pilocarpine-induced seizure it is suggested that the reduction of inhibitory amino acid neurotransmitters was comparatively minor and offset by a pronounced reduction of glutamate and aspartate. Therefore, like VPA, the finding that VPU could drastically reduce pilocarpine-induced increases in glutamate and aspartate should account, at least partly, for its anticonvulsant activity observed in pilocarpine-induced seizure in experimental animals. Some other mechanism than those being reported herein should be further investigated."],"offsets":[[127,1786]]}],"entities":[{"id":"20733","type":"Chemical","text":["N-(2-propylpentanoyl)urea"],"offsets":[[17,42]],"normalized":[{"db_name":"MESH","db_id":"C108761"}]},{"id":"20734","type":"Chemical","text":["amino acid"],"offsets":[[58,68]],"normalized":[{"db_name":"MESH","db_id":"D000596"}]},{"id":"20735","type":"Chemical","text":["pilocarpine"],"offsets":[[90,101]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"20736","type":"Disease","text":["seizure"],"offsets":[[110,117]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"20737","type":"Chemical","text":["amino 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{"id":"20807","document_id":"17919553","passages":[{"id":"20808","type":"title","text":["Acute hepatitis attack after exposure to telithromycin."],"offsets":[[0,55]]},{"id":"20809","type":"abstract","text":["INTRODUCTION: Antibiotic-associated hepatotoxicity is rare. With widespread use of antimicrobial agents, however, hepatic injury occurs frequently, and among adverse drug reactions, idiosyncratic reactions are the most serious. CASE SUMMARY: A 25-year-old male patient, with a height of 175 cm and weight of 72 kg presented to Marmara University Hospital Emergency Department, Istanbul, Turkey, with 5 days' history of jaundice, malaise, nausea, and vomiting. He had been prescribed telithromycin 400 mg\/d PO to treat an upper respiratory tract infection 7 days prior. Admission laboratory tests were as follows: alanine aminotransferase, 67 U\/L (reference range, 10-37 U\/L); aspartate aminotransferase, 98 U\/L (10-40 U\/L); alkaline phosphatase, 513 U\/L (0-270 U\/L); gamma-glutamyltransferase, 32 U\/L (7-49 U\/L); amylase, 46 U\/L (0-220 U\/L); total bilirubin, 20.1 mg\/dL (0.2-1.0 mg\/dL); direct bilirubin, 14.8 mg\/dL (0-0.3 mg\/dL); and albumin, 4.7 mg\/dL (3.5-5.4 mg\/dL). No toxin, alcohol, or other drugs were reported. The patient had suffered a previous episode of \"acute hepatitis of unknown origin,\" that occurred after telithromycin usage. Both incidents occurred within a year. DISCUSSION: Telithromycin is the first of the ketolide antibacterials to receive US Food and Drug Administration approval for clinical use. It has been associated with infrequent and usually reversible severe hepatic dysfunction. Based on a score of 8 on the Naranjo adverse drug reaction probability scale, telithromycin was the probable cause of acute hepatitis in this patient, and pathological findings suggested drug-induced toxic hepatitis. Recurrence of hepatitis attack might have been avoided if the initial incident had been communicated to the attending physician who prescribed telithromycin the second time. CONCLUSION: Here we report a case of acute hepatitis probably associated with the administration of telithromycin."],"offsets":[[56,1975]]}],"entities":[{"id":"20810","type":"Disease","text":["hepatitis"],"offsets":[[6,15]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"20811","type":"Chemical","text":["telithromycin"],"offsets":[[41,54]],"normalized":[{"db_name":"MESH","db_id":"C106791"}]},{"id":"20812","type":"Disease","text":["hepatotoxicity"],"offsets":[[92,106]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"20813","type":"Disease","text":["hepatic injury"],"offsets":[[170,184]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"20814","type":"Disease","text":["adverse drug 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{"id":"20893","document_id":"15632880","passages":[{"id":"20894","type":"title","text":["Spironolactone-induced renal insufficiency and hyperkalemia in patients with heart failure."],"offsets":[[0,91]]},{"id":"20895","type":"abstract","text":["BACKGROUND: A previous randomized controlled trial evaluating the use of spironolactone in heart failure patients reported a low risk of hyperkalemia (2%) and renal insufficiency (0%). Because treatments for heart failure have changed since the benefits of spironolactone were reported, the prevalence of these complications may differ in current clinical practice. We therefore sought to determine the prevalence and clinical associations of hyperkalemia and renal insufficiency in heart failure patients treated with spironolactone. METHODS: We performed a case control study of heart failure patients treated with spironolactone in our clinical practice. Cases were patients who developed hyperkalemia (K(+) >5.0 mEq\/L) or renal insufficiency (Cr >or=2.5 mg\/dL), and they were compared to 2 randomly selected controls per case. Clinical characteristics, medications, and serum chemistries at baseline and follow-up time periods were compared. RESULTS: Sixty-seven of 926 patients (7.2%) required discontinuation of spironolactone due to hyperkalemia (n = 33) or renal failure (n = 34). Patients who developed hyperkalemia were older and more likely to have diabetes, had higher baseline serum potassium levels and lower baseline potassium supplement doses, and were more likely to be treated with beta-blockers than controls (n = 134). Patients who developed renal insufficiency had lower baseline body weight and higher baseline serum creatinine, required higher doses of loop diuretics, and were more likely to be treated with thiazide diuretics than controls. CONCLUSIONS: Spironolactone-induced hyperkalemia and renal insufficiency are more common in our clinical experience than reported previously. This difference is explained by patient comorbidities and more frequent use of beta-blockers."],"offsets":[[92,1893]]}],"entities":[{"id":"20896","type":"Chemical","text":["Spironolactone"],"offsets":[[0,14]],"normalized":[{"db_name":"MESH","db_id":"D013148"}]},{"id":"20897","type":"Disease","text":["renal insufficiency"],"offsets":[[23,42]],"normalized":[{"db_name":"MESH","db_id":"D051437"}]},{"id":"20898","type":"Disease","text":["hyperkalemia"],"offsets":[[47,59]],"normalized":[{"db_name":"MESH","db_id":"D006947"}]},{"id":"20899","type":"Disease","text":["heart failure"],"offsets":[[77,90]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]},{"id":"20900","type":"Chemical","text":["spironolactone"],"offsets":[[165,179]],"normalized":[{"db_name":"MESH","db_id":"D013148"}]},{"id":"20901","type":"Disease","text":["heart 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{"id":"21027","document_id":"11773892","passages":[{"id":"21028","type":"title","text":["End-stage renal disease (ESRD) after orthotopic liver transplantation (OLTX) using calcineurin-based immunotherapy: risk of development and treatment."],"offsets":[[0,150]]},{"id":"21029","type":"abstract","text":["BACKGROUND: The calcineurin inhibitors cyclosporine and tacrolimus are both known to be nephrotoxic. Their use in orthotopic liver transplantation (OLTX) has dramatically improved success rates. Recently, however, we have had an increase of patients who are presenting after OLTX with end-stage renal disease (ESRD). This retrospective study examines the incidence and treatment of ESRD and chronic renal failure (CRF) in OLTX patients. METHODS: Patients receiving an OLTX only from June 1985 through December of 1994 who survived 6 months postoperatively were studied (n=834). Our prospectively collected database was the source of information. Patients were divided into three groups: Controls, no CRF or ESRD, n=748; CRF, sustained serum creatinine >2.5 mg\/dl, n=41; and ESRD, n=45. Groups were compared for preoperative laboratory variables, diagnosis, postoperative variables, survival, type of ESRD therapy, and survival from onset of ESRD. RESULTS: At 13 years after OLTX, the incidence of severe renal dysfunction was 18.1% (CRF 8.6% and ESRD 9.5%). Compared with control patients, CRF and ESRD patients had higher preoperative serum creatinine levels, a greater percentage of patients with hepatorenal syndrome, higher percentage requirement for dialysis in the first 3 months postoperatively, and a higher 1-year serum creatinine. Multivariate stepwise logistic regression analysis using preoperative and postoperative variables identified that an increase of serum creatinine compared with average at 1 year, 3 months, and 4 weeks postoperatively were independent risk factors for the development of CRF or ESRD with odds ratios of 2.6, 2.2, and 1.6, respectively. Overall survival from the time of OLTX was not significantly different among groups, but by year 13, the survival of the patients who had ESRD was only 28.2% compared with 54.6% in the control group. Patients developing ESRD had a 6-year survival after onset of ESRD of 27% for the patients receiving hemodialysis versus 71.4% for the patients developing ESRD who subsequently received kidney transplants. CONCLUSIONS: Patients who are more than 10 years post-OLTX have CRF and ESRD at a high rate. The development of ESRD decreases survival, particularly in those patients treated with dialysis only. Patients who develop ESRD have a higher preoperative and 1-year serum creatinine and are more likely to have hepatorenal syndrome. However, an increase of serum creatinine at various times postoperatively is more predictive of the development of CRF or ESRD. New strategies for long-term immunosuppression may be needed to decrease this complication."],"offsets":[[151,2779]]}],"entities":[{"id":"21030","type":"Disease","text":["End-stage renal disease"],"offsets":[[0,23]],"normalized":[{"db_name":"MESH","db_id":"D007676"}]},{"id":"21031","type":"Disease","text":["ESRD"],"offsets":[[25,29]],"normalized":[{"db_name":"MESH","db_id":"D007676"}]},{"id":"21032","type":"Chemical","text":["cyclosporine"],"offsets":[[190,202]],"normalized":[{"db_name":"MESH","db_id":"D016572"}]},{"id":"21033","type":"Chemical","text":["tacrolimus"],"offsets":[[207,217]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"21034","type":"Disease","text":["nephrotoxic"],"offsets":[[239,250]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"21035","type":"Disease","text":["end-stage renal disease"],"offsets":[[436,459]],"normalized":[{"db_name":"MESH","db_id":"D007676"}]},{"id":"21036","type":"Disease","text":["ESRD"],"offsets":[[461,465]],"normalized":[{"db_name":"MESH","db_id":"D007676"}]},{"id":"21037","type":"Disease","text":["ESRD"],"offsets":[[533,537]],"normalized":[{"db_name":"MESH","db_id":"D007676"}]},{"id":"21038","type":"Disease","text":["chronic renal failure"],"offsets":[[542,563]],"normalized":[{"db_name":"MESH","db_id":"D007676"}]},{"id":"21039","type":"Disease","text":["CRF"],"offsets":[[565,568]],"normalized":[{"db_name":"MESH","db_id":"D007676"}]},{"id":"21040","type":"Disease","text":["CRF"],"offsets":[[851,854]],"normalized":[{"db_name":"MESH","db_id":"D007676"}]},{"id":"21041","type":"Disease","text":["ESRD"],"offsets":[[858,862]],"normalized":[{"db_name":"MESH","db_id":"D007676"}]},{"id":"21042","type":"Disease","text":["CRF"],"offsets":[[871,874]],"normalized":[{"db_name":"MESH","db_id":"D007676"}]},{"id":"21043","type":"Chemical","text":["creatinine"],"offsets":[[892,902]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"21044","type":"Disease","text":["ESRD"],"offsets":[[925,929]],"normalized":[{"db_name":"MESH","db_id":"D007676"}]},{"id":"21045","type":"Disease","text":["ESRD"],"offsets":[[1051,1055]],"normalized":[{"db_name":"MESH","db_id":"D007676"}]},{"id":"21046","type":"Disease","text":["ESRD"],"offsets":[[1092,1096]],"normalized":[{"db_name":"MESH","db_id":"D007676"}]},{"id":"21047","type":"Disease","text":["renal dysfunction"],"offsets":[[1155,1172]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"21048","type":"Disease","text":["CRF"],"offsets":[[1184,1187]],"normalized":[{"db_name":"MESH","db_id":"D007676"}]},{"id":"21049","type":"Disease","text":["ESRD"],"offsets":[[1197,1201]],"normalized":[{"db_name":"MESH","db_id":"D007676"}]},{"id":"21050","type":"Disease","text":["CRF"],"offsets":[[1241,1244]],"normalized":[{"db_name":"MESH","db_id":"D007676"}]},{"id":"21051","type":"Disease","text":["ESRD"],"offsets":[[1249,1253]],"normalized":[{"db_name":"MESH","db_id":"D007676"}]},{"id":"21052","type":"Chemical","text":["creatinine"],"offsets":[[1293,1303]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"21053","type":"Disease","text":["hepatorenal syndrome"],"offsets":[[1350,1370]],"normalized":[{"db_name":"MESH","db_id":"D006530"}]},{"id":"21054","type":"Chemical","text":["creatinine"],"offsets":[[1480,1490]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"21055","type":"Chemical","text":["creatinine"],"offsets":[[1627,1637]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"21056","type":"Disease","text":["CRF"],"offsets":[[1762,1765]],"normalized":[{"db_name":"MESH","db_id":"D007676"}]},{"id":"21057","type":"Disease","text":["ESRD"],"offsets":[[1769,1773]],"normalized":[{"db_name":"MESH","db_id":"D007676"}]},{"id":"21058","type":"Disease","text":["ESRD"],"offsets":[[1965,1969]],"normalized":[{"db_name":"MESH","db_id":"D007676"}]},{"id":"21059","type":"Disease","text":["ESRD"],"offsets":[[2047,2051]],"normalized":[{"db_name":"MESH","db_id":"D007676"}]},{"id":"21060","type":"Disease","text":["ESRD"],"offsets":[[2089,2093]],"normalized":[{"db_name":"MESH","db_id":"D007676"}]},{"id":"21061","type":"Disease","text":["ESRD"],"offsets":[[2182,2186]],"normalized":[{"db_name":"MESH","db_id":"D007676"}]},{"id":"21062","type":"Disease","text":["CRF"],"offsets":[[2297,2300]],"normalized":[{"db_name":"MESH","db_id":"D007676"}]},{"id":"21063","type":"Disease","text":["ESRD"],"offsets":[[2305,2309]],"normalized":[{"db_name":"MESH","db_id":"D007676"}]},{"id":"21064","type":"Disease","text":["ESRD"],"offsets":[[2345,2349]],"normalized":[{"db_name":"MESH","db_id":"D007676"}]},{"id":"21065","type":"Disease","text":["ESRD"],"offsets":[[2450,2454]],"normalized":[{"db_name":"MESH","db_id":"D007676"}]},{"id":"21066","type":"Chemical","text":["creatinine"],"offsets":[[2499,2509]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"21067","type":"Disease","text":["hepatorenal syndrome"],"offsets":[[2538,2558]],"normalized":[{"db_name":"MESH","db_id":"D006530"}]},{"id":"21068","type":"Chemical","text":["creatinine"],"offsets":[[2590,2600]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"21069","type":"Disease","text":["CRF"],"offsets":[[2675,2678]],"normalized":[{"db_name":"MESH","db_id":"D007676"}]},{"id":"21070","type":"Disease","text":["ESRD"],"offsets":[[2682,2686]],"normalized":[{"db_name":"MESH","db_id":"D007676"}]}],"events":[],"coreferences":[],"relations":[{"id":"21071","type":"CID","arg1_id":"21033","arg2_id":"21034","normalized":[]},{"id":"21072","type":"CID","arg1_id":"21033","arg2_id":"21047","normalized":[]},{"id":"21073","type":"CID","arg1_id":"21032","arg2_id":"21034","normalized":[]},{"id":"21074","type":"CID","arg1_id":"21032","arg2_id":"21047","normalized":[]}]}
{"id":"21075","document_id":"10835440","passages":[{"id":"21076","type":"title","text":["Effect of intravenous nimodipine on blood pressure and outcome after acute stroke."],"offsets":[[0,82]]},{"id":"21077","type":"abstract","text":["BACKGROUND AND PURPOSE: The Intravenous Nimodipine West European Stroke Trial (INWEST) found a correlation between nimodipine-induced reduction in blood pressure (BP) and an unfavorable outcome in acute stroke. We sought to confirm this correlation with and without adjustment for prognostic variables and to investigate outcome in subgroups with increasing levels of BP reduction. METHODS: Patients with a clinical diagnosis of ischemic stroke (within 24 hours) were consecutively allocated to receive placebo (n=100), 1 mg\/h (low-dose) nimodipine (n=101), or 2 mg\/h (high-dose) nimodipine (n=94). The correlation between average BP change during the first 2 days and the outcome at day 21 was analyzed. RESULTS: Two hundred sixty-five patients were included in this analysis (n=92, 93, and 80 for placebo, low dose, and high dose, respectively). Nimodipine treatment resulted in a statistically significant reduction in systolic BP (SBP) and diastolic BP (DBP) from baseline compared with placebo during the first few days. In multivariate analysis, a significant correlation between DBP reduction and worsening of the neurological score was found for the high-dose group (beta=0.49, P=0. 048). Patients with a DBP reduction of > or =20% in the high-dose group had a significantly increased adjusted OR for the compound outcome variable death or dependency (Barthel Index <60) (n\/N=25\/26, OR 10. 16, 95% CI 1.02 to 101.74) and death alone (n\/N=9\/26, OR 4.336, 95% CI 1.131 16.619) compared with all placebo patients (n\/N=62\/92 and 14\/92, respectively). There was no correlation between SBP change and outcome. CONCLUSIONS: DBP, but not SBP, reduction was associated with neurological worsening after the intravenous administration of high-dose nimodipine after acute stroke. For low-dose nimodipine, the results were not conclusive. These results do not confirm or exclude a neuroprotective property of nimodipine."],"offsets":[[83,1999]]}],"entities":[{"id":"21078","type":"Chemical","text":["nimodipine"],"offsets":[[22,32]],"normalized":[{"db_name":"MESH","db_id":"D009553"}]},{"id":"21079","type":"Disease","text":["acute stroke"],"offsets":[[69,81]],"normalized":[{"db_name":"MESH","db_id":"D020521"}]},{"id":"21080","type":"Chemical","text":["Nimodipine"],"offsets":[[123,133]],"normalized":[{"db_name":"MESH","db_id":"D009553"}]},{"id":"21081","type":"Disease","text":["Stroke"],"offsets":[[148,154]],"normalized":[{"db_name":"MESH","db_id":"D020521"}]},{"id":"21082","type":"Chemical","text":["nimodipine"],"offsets":[[198,208]],"normalized":[{"db_name":"MESH","db_id":"D009553"}]},{"id":"21083","type":"Disease","text":["reduction in blood pressure"],"offsets":[[217,244]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"21084","type":"Disease","text":["acute stroke"],"offsets":[[280,292]],"normalized":[{"db_name":"MESH","db_id":"D020521"}]},{"id":"21085","type":"Disease","text":["BP reduction"],"offsets":[[451,463]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"21086","type":"Disease","text":["ischemic stroke"],"offsets":[[512,527]],"normalized":[{"db_name":"MESH","db_id":"D002544"}]},{"id":"21087","type":"Chemical","text":["nimodipine"],"offsets":[[621,631]],"normalized":[{"db_name":"MESH","db_id":"D009553"}]},{"id":"21088","type":"Chemical","text":["nimodipine"],"offsets":[[663,673]],"normalized":[{"db_name":"MESH","db_id":"D009553"}]},{"id":"21089","type":"Chemical","text":["Nimodipine"],"offsets":[[931,941]],"normalized":[{"db_name":"MESH","db_id":"D009553"}]},{"id":"21090","type":"Disease","text":["reduction in systolic BP"],"offsets":[[992,1016]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"21091","type":"Disease","text":["DBP reduction"],"offsets":[[1169,1182]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"21092","type":"Disease","text":["DBP reduction"],"offsets":[[1296,1309]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"21093","type":"Disease","text":["death"],"offsets":[[1422,1427]],"normalized":[{"db_name":"MESH","db_id":"D003643"}]},{"id":"21094","type":"Disease","text":["death"],"offsets":[[1512,1517]],"normalized":[{"db_name":"MESH","db_id":"D003643"}]},{"id":"21095","type":"Chemical","text":["nimodipine"],"offsets":[[1829,1839]],"normalized":[{"db_name":"MESH","db_id":"D009553"}]},{"id":"21096","type":"Disease","text":["acute stroke"],"offsets":[[1846,1858]],"normalized":[{"db_name":"MESH","db_id":"D020521"}]},{"id":"21097","type":"Chemical","text":["nimodipine"],"offsets":[[1873,1883]],"normalized":[{"db_name":"MESH","db_id":"D009553"}]},{"id":"21098","type":"Chemical","text":["nimodipine"],"offsets":[[1988,1998]],"normalized":[{"db_name":"MESH","db_id":"D009553"}]}],"events":[],"coreferences":[],"relations":[{"id":"21099","type":"CID","arg1_id":"21078","arg2_id":"21083","normalized":[]},{"id":"21100","type":"CID","arg1_id":"21078","arg2_id":"21085","normalized":[]},{"id":"21101","type":"CID","arg1_id":"21078","arg2_id":"21090","normalized":[]},{"id":"21102","type":"CID","arg1_id":"21078","arg2_id":"21091","normalized":[]},{"id":"21103","type":"CID","arg1_id":"21078","arg2_id":"21092","normalized":[]},{"id":"21104","type":"CID","arg1_id":"21080","arg2_id":"21083","normalized":[]},{"id":"21105","type":"CID","arg1_id":"21080","arg2_id":"21085","normalized":[]},{"id":"21106","type":"CID","arg1_id":"21080","arg2_id":"21090","normalized":[]},{"id":"21107","type":"CID","arg1_id":"21080","arg2_id":"21091","normalized":[]},{"id":"21108","type":"CID","arg1_id":"21080","arg2_id":"21092","normalized":[]},{"id":"21109","type":"CID","arg1_id":"21082","arg2_id":"21083","normalized":[]},{"id":"21110","type":"CID","arg1_id":"21082","arg2_id":"21085","normalized":[]},{"id":"21111","type":"CID","arg1_id":"21082","arg2_id":"21090","normalized":[]},{"id":"21112","type":"CID","arg1_id":"21082","arg2_id":"21091","normalized":[]},{"id":"21113","type":"CID","arg1_id":"21082","arg2_id":"21092","normalized":[]},{"id":"21114","type":"CID","arg1_id":"21087","arg2_id":"21083","normalized":[]},{"id":"21115","type":"CID","arg1_id":"21087","arg2_id":"21085","normalized":[]},{"id":"21116","type":"CID","arg1_id":"21087","arg2_id":"21090","normalized":[]},{"id":"21117","type":"CID","arg1_id":"21087","arg2_id":"21091","normalized":[]},{"id":"21118","type":"CID","arg1_id":"21087","arg2_id":"21092","normalized":[]},{"id":"21119","type":"CID","arg1_id":"21088","arg2_id":"21083","normalized":[]},{"id":"21120","type":"CID","arg1_id":"21088","arg2_id":"21085","normalized":[]},{"id":"21121","type":"CID","arg1_id":"21088","arg2_id":"21090","normalized":[]},{"id":"21122","type":"CID","arg1_id":"21088","arg2_id":"21091","normalized":[]},{"id":"21123","type":"CID","arg1_id":"21088","arg2_id":"21092","normalized":[]},{"id":"21124","type":"CID","arg1_id":"21089","arg2_id":"21083","normalized":[]},{"id":"21125","type":"CID","arg1_id":"21089","arg2_id":"21085","normalized":[]},{"id":"21126","type":"CID","arg1_id":"21089","arg2_id":"21090","normalized":[]},{"id":"21127","type":"CID","arg1_id":"21089","arg2_id":"21091","normalized":[]},{"id":"21128","type":"CID","arg1_id":"21089","arg2_id":"21092","normalized":[]},{"id":"21129","type":"CID","arg1_id":"21095","arg2_id":"21083","normalized":[]},{"id":"21130","type":"CID","arg1_id":"21095","arg2_id":"21085","normalized":[]},{"id":"21131","type":"CID","arg1_id":"21095","arg2_id":"21090","normalized":[]},{"id":"21132","type":"CID","arg1_id":"21095","arg2_id":"21091","normalized":[]},{"id":"21133","type":"CID","arg1_id":"21095","arg2_id":"21092","normalized":[]},{"id":"21134","type":"CID","arg1_id":"21097","arg2_id":"21083","normalized":[]},{"id":"21135","type":"CID","arg1_id":"21097","arg2_id":"21085","normalized":[]},{"id":"21136","type":"CID","arg1_id":"21097","arg2_id":"21090","normalized":[]},{"id":"21137","type":"CID","arg1_id":"21097","arg2_id":"21091","normalized":[]},{"id":"21138","type":"CID","arg1_id":"21097","arg2_id":"21092","normalized":[]},{"id":"21139","type":"CID","arg1_id":"21098","arg2_id":"21083","normalized":[]},{"id":"21140","type":"CID","arg1_id":"21098","arg2_id":"21085","normalized":[]},{"id":"21141","type":"CID","arg1_id":"21098","arg2_id":"21090","normalized":[]},{"id":"21142","type":"CID","arg1_id":"21098","arg2_id":"21091","normalized":[]},{"id":"21143","type":"CID","arg1_id":"21098","arg2_id":"21092","normalized":[]}]}
{"id":"21144","document_id":"9523805","passages":[{"id":"21145","type":"title","text":["Transient neurologic symptoms after spinal anesthesia: a lower incidence with prilocaine and bupivacaine than with lidocaine."],"offsets":[[0,125]]},{"id":"21146","type":"abstract","text":["BACKGROUND: Recent evidence suggests that transient neurologic symptoms (TNSs) frequently follow lidocaine spinal anesthesia but are infrequent with bupivacaine. However, identification of a short-acting local anesthetic to substitute for lidocaine for brief surgical procedures remains an important goal. Prilocaine is an amide local anesthetic with a duration of action similar to that of lidocaine. Accordingly, the present, prospective double-blind study compares prilocaine with lidocaine and bupivacaine with respect to duration of action and relative risk of TNSs. METHODS: Ninety patients classified as American Society of Anesthesiologists physical status I or II who were scheduled for short gynecologic procedures under spinal anesthesia were randomly allocated to receive 2.5 ml 2% lidocaine in 7.5% glucose, 2% prilocaine in 7.5% glucose, or 0.5% bupivacaine in 7.5% glucose. All solutions were provided in blinded vials by the hospital pharmacy. Details of spinal puncture, extension and regression of spinal block, and the times to reach discharge criteria were noted. In the evening of postoperative day 1, patients were evaluated for TNSs by a physician unaware of the drug administered and the details of the anesthetic procedure. RESULTS: Nine of 30 patients receiving lidocaine experienced TNSs, 1 of 30 patients receiving prilocaine (P = 0.03) had them, and none of 30 patients receiving bupivacaine had TNSs. Times to ambulate and to void were similar after lidocaine and prilocaine (150 vs. 165 min and 238 vs. 253 min, respectively) but prolonged after bupivacaine (200 and 299 min, respectively; P < 0.05). CONCLUSIONS: Prilocaine may be preferable to lidocaine for short surgical procedures because it has a similar duration of action but a lower incidence of TNSs."],"offsets":[[126,1917]]}],"entities":[{"id":"21147","type":"Disease","text":["Transient neurologic symptoms"],"offsets":[[0,29]],"normalized":[{"db_name":"MESH","db_id":"D009422"}]},{"id":"21148","type":"Chemical","text":["prilocaine"],"offsets":[[78,88]],"normalized":[{"db_name":"MESH","db_id":"D011318"}]},{"id":"21149","type":"Chemical","text":["bupivacaine"],"offsets":[[93,104]],"normalized":[{"db_name":"MESH","db_id":"D002045"}]},{"id":"21150","type":"Chemical","text":["lidocaine"],"offsets":[[115,124]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"21151","type":"Disease","text":["transient neurologic 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{"id":"21308","document_id":"9245658","passages":[{"id":"21309","type":"title","text":["The role of nicotine in smoking-related cardiovascular disease."],"offsets":[[0,63]]},{"id":"21310","type":"abstract","text":["Nicotine activates the sympathetic nervous system and in this way could contribute to cardiovascular disease. Animal studies and mechanistic studies indicate that nicotine could play a role in accelerating atherosclerosis, but evidence among humans is too inadequate to be definitive about such an effect. Almost certainly, nicotine via its hemodynamic effects contributes to acute cardiovascular events, although current evidence suggests that the effects of nicotine are much less important than are the prothrombotic effects of cigarette smoking or the effects of carbon monoxide. Nicotine does not appear to enhance thrombosis among humans. Clinical studies of pipe smokers and people using transdermal nicotine support the idea that toxins other than nicotine are the most important causes of acute cardiovascular events. Finally, the dose response for cardiovascular events of nicotine appears to be flat, suggesting that if nicotine is involved, adverse effects might be seen with relatively low-level cigarette exposures."],"offsets":[[64,1093]]}],"entities":[{"id":"21311","type":"Chemical","text":["nicotine"],"offsets":[[12,20]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"21312","type":"Disease","text":["cardiovascular disease"],"offsets":[[40,62]],"normalized":[{"db_name":"MESH","db_id":"D002318"}]},{"id":"21313","type":"Chemical","text":["Nicotine"],"offsets":[[64,72]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"21314","type":"Disease","text":["cardiovascular disease"],"offsets":[[150,172]],"normalized":[{"db_name":"MESH","db_id":"D002318"}]},{"id":"21315","type":"Chemical","text":["nicotine"],"offsets":[[227,235]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"21316","type":"Disease","text":["atherosclerosis"],"offsets":[[270,285]],"normalized":[{"db_name":"MESH","db_id":"D050197"}]},{"id":"21317","type":"Chemical","text":["nicotine"],"offsets":[[388,396]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"21318","type":"Chemical","text":["nicotine"],"offsets":[[524,532]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"21319","type":"Chemical","text":["carbon monoxide"],"offsets":[[631,646]],"normalized":[{"db_name":"MESH","db_id":"D002248"}]},{"id":"21320","type":"Chemical","text":["Nicotine"],"offsets":[[648,656]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"21321","type":"Disease","text":["thrombosis"],"offsets":[[684,694]],"normalized":[{"db_name":"MESH","db_id":"D013927"}]},{"id":"21322","type":"Chemical","text":["nicotine"],"offsets":[[771,779]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"21323","type":"Chemical","text":["nicotine"],"offsets":[[820,828]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"21324","type":"Chemical","text":["nicotine"],"offsets":[[947,955]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"21325","type":"Chemical","text":["nicotine"],"offsets":[[995,1003]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]}],"events":[],"coreferences":[],"relations":[{"id":"21326","type":"CID","arg1_id":"21311","arg2_id":"21312","normalized":[]},{"id":"21327","type":"CID","arg1_id":"21311","arg2_id":"21314","normalized":[]},{"id":"21328","type":"CID","arg1_id":"21313","arg2_id":"21312","normalized":[]},{"id":"21329","type":"CID","arg1_id":"21313","arg2_id":"21314","normalized":[]},{"id":"21330","type":"CID","arg1_id":"21315","arg2_id":"21312","normalized":[]},{"id":"21331","type":"CID","arg1_id":"21315","arg2_id":"21314","normalized":[]},{"id":"21332","type":"CID","arg1_id":"21317","arg2_id":"21312","normalized":[]},{"id":"21333","type":"CID","arg1_id":"21317","arg2_id":"21314","normalized":[]},{"id":"21334","type":"CID","arg1_id":"21318","arg2_id":"21312","normalized":[]},{"id":"21335","type":"CID","arg1_id":"21318","arg2_id":"21314","normalized":[]},{"id":"21336","type":"CID","arg1_id":"21320","arg2_id":"21312","normalized":[]},{"id":"21337","type":"CID","arg1_id":"21320","arg2_id":"21314","normalized":[]},{"id":"21338","type":"CID","arg1_id":"21322","arg2_id":"21312","normalized":[]},{"id":"21339","type":"CID","arg1_id":"21322","arg2_id":"21314","normalized":[]},{"id":"21340","type":"CID","arg1_id":"21323","arg2_id":"21312","normalized":[]},{"id":"21341","type":"CID","arg1_id":"21323","arg2_id":"21314","normalized":[]},{"id":"21342","type":"CID","arg1_id":"21324","arg2_id":"21312","normalized":[]},{"id":"21343","type":"CID","arg1_id":"21324","arg2_id":"21314","normalized":[]},{"id":"21344","type":"CID","arg1_id":"21325","arg2_id":"21312","normalized":[]},{"id":"21345","type":"CID","arg1_id":"21325","arg2_id":"21314","normalized":[]},{"id":"21346","type":"CID","arg1_id":"21311","arg2_id":"21316","normalized":[]},{"id":"21347","type":"CID","arg1_id":"21313","arg2_id":"21316","normalized":[]},{"id":"21348","type":"CID","arg1_id":"21315","arg2_id":"21316","normalized":[]},{"id":"21349","type":"CID","arg1_id":"21317","arg2_id":"21316","normalized":[]},{"id":"21350","type":"CID","arg1_id":"21318","arg2_id":"21316","normalized":[]},{"id":"21351","type":"CID","arg1_id":"21320","arg2_id":"21316","normalized":[]},{"id":"21352","type":"CID","arg1_id":"21322","arg2_id":"21316","normalized":[]},{"id":"21353","type":"CID","arg1_id":"21323","arg2_id":"21316","normalized":[]},{"id":"21354","type":"CID","arg1_id":"21324","arg2_id":"21316","normalized":[]},{"id":"21355","type":"CID","arg1_id":"21325","arg2_id":"21316","normalized":[]}]}
{"id":"21356","document_id":"9034419","passages":[{"id":"21357","type":"title","text":["Seizure resulting from a venlafaxine overdose."],"offsets":[[0,46]]},{"id":"21358","type":"abstract","text":["OBJECTIVE: To report a case of venlafaxine overdose. CASE SUMMARY: A 40-year-old woman with major depression took an overdose of venlafaxine in an apparent suicide attempt. After the ingestion of 26 venlafaxine 50-mg tablets, the patient experienced a witnessed generalized seizure. She was admitted to the medical intensive care unit, venlafaxine was discontinued, and no further sequelae were seen. DISCUSSION: To our knowledge, this is the first reported case of venlafaxine overdose that resulted in a generalized seizure. Based on nonoverdose pharmacokinetics and pharmacodynamics of venlafaxine and the potential risks of available interventions, no emergent therapy was instituted. CONCLUSIONS: The venlafaxine overdose in our patient resulted in a single episode of generalized seizure but elicited no further sequelae."],"offsets":[[47,874]]}],"entities":[{"id":"21359","type":"Disease","text":["Seizure"],"offsets":[[0,7]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"21360","type":"Chemical","text":["venlafaxine"],"offsets":[[25,36]],"normalized":[{"db_name":"MESH","db_id":"C047426"}]},{"id":"21361","type":"Disease","text":["overdose"],"offsets":[[37,45]],"normalized":[{"db_name":"MESH","db_id":"D062787"}]},{"id":"21362","type":"Chemical","text":["venlafaxine"],"offsets":[[78,89]],"normalized":[{"db_name":"MESH","db_id":"C047426"}]},{"id":"21363","type":"Disease","text":["overdose"],"offsets":[[90,98]],"normalized":[{"db_name":"MESH","db_id":"D062787"}]},{"id":"21364","type":"Disease","text":["major 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{"id":"21449","document_id":"8829025","passages":[{"id":"21450","type":"title","text":["Effect of nifedipine on renal function in liver transplant recipients receiving tacrolimus."],"offsets":[[0,91]]},{"id":"21451","type":"abstract","text":["The effect of nifedipine on renal function in liver transplant recipients who were receiving tacrolimus was evaluated between January 1992 and January 1996. Two groups of patients receiving tacrolimus were compared over a period of 1 year, one group comprising hypertensive patients who were receiving nifedipine, and the other comprising nonhypertensive patients not receiving nifedipine. The time from transplant to baseline was similar in all patients. Nifedipine significantly improved kidney function as indicated by a significant lowering of serum creatinine levels at 6 and 12 months. The observed positive impact of nifedipine on reducing the nephrotoxicity associated with tacrolimus in liver transplant recipients should be an important factor in selecting an agent to treat hypertension in this population."],"offsets":[[92,909]]}],"entities":[{"id":"21452","type":"Chemical","text":["nifedipine"],"offsets":[[10,20]],"normalized":[{"db_name":"MESH","db_id":"D009543"}]},{"id":"21453","type":"Chemical","text":["tacrolimus"],"offsets":[[80,90]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"21454","type":"Chemical","text":["nifedipine"],"offsets":[[106,116]],"normalized":[{"db_name":"MESH","db_id":"D009543"}]},{"id":"21455","type":"Chemical","text":["tacrolimus"],"offsets":[[185,195]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"21456","type":"Chemical","text":["tacrolimus"],"offsets":[[282,292]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"21457","type":"Disease","text":["hypertensive"],"offsets":[[353,365]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"21458","type":"Chemical","text":["nifedipine"],"offsets":[[394,404]],"normalized":[{"db_name":"MESH","db_id":"D009543"}]},{"id":"21459","type":"Chemical","text":["nifedipine"],"offsets":[[470,480]],"normalized":[{"db_name":"MESH","db_id":"D009543"}]},{"id":"21460","type":"Chemical","text":["Nifedipine"],"offsets":[[548,558]],"normalized":[{"db_name":"MESH","db_id":"D009543"}]},{"id":"21461","type":"Chemical","text":["creatinine"],"offsets":[[646,656]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"21462","type":"Chemical","text":["nifedipine"],"offsets":[[716,726]],"normalized":[{"db_name":"MESH","db_id":"D009543"}]},{"id":"21463","type":"Disease","text":["nephrotoxicity"],"offsets":[[743,757]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"21464","type":"Chemical","text":["tacrolimus"],"offsets":[[774,784]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"21465","type":"Disease","text":["hypertension"],"offsets":[[877,889]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]}],"events":[],"coreferences":[],"relations":[{"id":"21466","type":"CID","arg1_id":"21453","arg2_id":"21457","normalized":[]},{"id":"21467","type":"CID","arg1_id":"21453","arg2_id":"21465","normalized":[]},{"id":"21468","type":"CID","arg1_id":"21455","arg2_id":"21457","normalized":[]},{"id":"21469","type":"CID","arg1_id":"21455","arg2_id":"21465","normalized":[]},{"id":"21470","type":"CID","arg1_id":"21456","arg2_id":"21457","normalized":[]},{"id":"21471","type":"CID","arg1_id":"21456","arg2_id":"21465","normalized":[]},{"id":"21472","type":"CID","arg1_id":"21464","arg2_id":"21457","normalized":[]},{"id":"21473","type":"CID","arg1_id":"21464","arg2_id":"21465","normalized":[]}]}
{"id":"21474","document_id":"8437969","passages":[{"id":"21475","type":"title","text":["Sinus arrest associated with continuous-infusion cimetidine."],"offsets":[[0,60]]},{"id":"21476","type":"abstract","text":["The administration of intermittent intravenous infusions of cimetidine is infrequently associated with the development of bradyarrhythmias. A 40-year-old man with leukemia and no history of cardiac disease developed recurrent, brief episodes of apparent sinus arrest while receiving continuous-infusion cimetidine 50 mg\/hour. The arrhythmias were temporally related to cimetidine administration, disappeared after dechallenge, and did not recur during ranitidine treatment. This is the first reported case of sinus arrest associated with continuous-infusion cimetidine."],"offsets":[[61,630]]}],"entities":[{"id":"21477","type":"Disease","text":["Sinus arrest"],"offsets":[[0,12]],"normalized":[{"db_name":"MESH","db_id":"D054138"}]},{"id":"21478","type":"Chemical","text":["cimetidine"],"offsets":[[49,59]],"normalized":[{"db_name":"MESH","db_id":"D002927"}]},{"id":"21479","type":"Chemical","text":["cimetidine"],"offsets":[[121,131]],"normalized":[{"db_name":"MESH","db_id":"D002927"}]},{"id":"21480","type":"Disease","text":["bradyarrhythmias"],"offsets":[[183,199]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"21481","type":"Disease","text":["leukemia"],"offsets":[[224,232]],"normalized":[{"db_name":"MESH","db_id":"D007938"}]},{"id":"21482","type":"Disease","text":["cardiac disease"],"offsets":[[251,266]],"normalized":[{"db_name":"MESH","db_id":"D006331"}]},{"id":"21483","type":"Disease","text":["sinus arrest"],"offsets":[[315,327]],"normalized":[{"db_name":"MESH","db_id":"D054138"}]},{"id":"21484","type":"Chemical","text":["cimetidine"],"offsets":[[364,374]],"normalized":[{"db_name":"MESH","db_id":"D002927"}]},{"id":"21485","type":"Disease","text":["arrhythmias"],"offsets":[[391,402]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"21486","type":"Chemical","text":["cimetidine"],"offsets":[[430,440]],"normalized":[{"db_name":"MESH","db_id":"D002927"}]},{"id":"21487","type":"Chemical","text":["ranitidine"],"offsets":[[513,523]],"normalized":[{"db_name":"MESH","db_id":"D011899"}]},{"id":"21488","type":"Disease","text":["sinus arrest"],"offsets":[[570,582]],"normalized":[{"db_name":"MESH","db_id":"D054138"}]},{"id":"21489","type":"Chemical","text":["cimetidine"],"offsets":[[619,629]],"normalized":[{"db_name":"MESH","db_id":"D002927"}]}],"events":[],"coreferences":[],"relations":[{"id":"21490","type":"CID","arg1_id":"21478","arg2_id":"21477","normalized":[]},{"id":"21491","type":"CID","arg1_id":"21478","arg2_id":"21483","normalized":[]},{"id":"21492","type":"CID","arg1_id":"21478","arg2_id":"21488","normalized":[]},{"id":"21493","type":"CID","arg1_id":"21479","arg2_id":"21477","normalized":[]},{"id":"21494","type":"CID","arg1_id":"21479","arg2_id":"21483","normalized":[]},{"id":"21495","type":"CID","arg1_id":"21479","arg2_id":"21488","normalized":[]},{"id":"21496","type":"CID","arg1_id":"21484","arg2_id":"21477","normalized":[]},{"id":"21497","type":"CID","arg1_id":"21484","arg2_id":"21483","normalized":[]},{"id":"21498","type":"CID","arg1_id":"21484","arg2_id":"21488","normalized":[]},{"id":"21499","type":"CID","arg1_id":"21486","arg2_id":"21477","normalized":[]},{"id":"21500","type":"CID","arg1_id":"21486","arg2_id":"21483","normalized":[]},{"id":"21501","type":"CID","arg1_id":"21486","arg2_id":"21488","normalized":[]},{"id":"21502","type":"CID","arg1_id":"21489","arg2_id":"21477","normalized":[]},{"id":"21503","type":"CID","arg1_id":"21489","arg2_id":"21483","normalized":[]},{"id":"21504","type":"CID","arg1_id":"21489","arg2_id":"21488","normalized":[]},{"id":"21505","type":"CID","arg1_id":"21478","arg2_id":"21480","normalized":[]},{"id":"21506","type":"CID","arg1_id":"21479","arg2_id":"21480","normalized":[]},{"id":"21507","type":"CID","arg1_id":"21484","arg2_id":"21480","normalized":[]},{"id":"21508","type":"CID","arg1_id":"21486","arg2_id":"21480","normalized":[]},{"id":"21509","type":"CID","arg1_id":"21489","arg2_id":"21480","normalized":[]}]}
{"id":"21510","document_id":"7890216","passages":[{"id":"21511","type":"title","text":["Composition of gall bladder stones associated with octreotide: response to oral ursodeoxycholic acid."],"offsets":[[0,101]]},{"id":"21512","type":"abstract","text":["Octreotide, an effective treatment for acromegaly, induces gall bladder stones in 13-60% of patients. Because knowledge of stone composition is essential for studies of their pathogenesis, treatment, and prevention, this was investigated by direct and indirect methods in 14 octreotide treated acromegalic patients with gall stones. Chemical analysis of gall stones retrieved at cholecystectomy from two patients, showed that they contained 71% and 87% cholesterol by weight. In the remaining 12 patients, localised computed tomography of the gall bladder showed that eight had stones with maximum attenuation scores of < 100 Hounsfield units (values of < 100 HU predict cholesterol rich, dissolvable stones). Gall bladder bile was obtained by ultrasound guided, fine needle puncture from six patients. All six patients had supersaturated bile (mean (SEM) cholesterol saturation index of 1.19 (0.08) (range 1.01-1.53)) and all had abnormally rapid cholesterol microcrystal nucleation times (< 4 days (range 1-4)), whilst in four, the bile contained cholesterol microcrystals immediately after sampling. Of the 12 patients considered for oral ursodeoxycholic acid (UDCA) treatment, two had a blocked cystic duct and were not started on UDCA while one was lost to follow up. After one year of treatment, five of the remaining nine patients showed either partial (n = 3) or complete (n = 2) gall stone dissolution, suggesting that their stones were cholesterol rich. This corresponds, by actuarial (life table) analysis, to a combined gall stone dissolution rate of 58.3 (15.9%). In conclusion, octreotide induced gall stones are generally small, multiple, and cholesterol rich although, in common with spontaneous gall stone disease, at presentation some patients will have a blocked cystic duct and some gall stones containing calcium."],"offsets":[[102,1936]]}],"entities":[{"id":"21513","type":"Disease","text":["gall bladder stones"],"offsets":[[15,34]],"normalized":[{"db_name":"MESH","db_id":"D042882"}]},{"id":"21514","type":"Chemical","text":["octreotide"],"offsets":[[51,61]],"normalized":[{"db_name":"MESH","db_id":"D015282"}]},{"id":"21515","type":"Chemical","text":["ursodeoxycholic acid"],"offsets":[[80,100]],"normalized":[{"db_name":"MESH","db_id":"D014580"}]},{"id":"21516","type":"Chemical","text":["Octreotide"],"offsets":[[102,112]],"normalized":[{"db_name":"MESH","db_id":"D015282"}]},{"id":"21517","type":"Disease","text":["acromegaly"],"offsets":[[141,151]],"normalized":[{"db_name":"MESH","db_id":"D000172"}]},{"id":"21518","type":"Disease","text":["gall bladder stones"],"offsets":[[161,180]],"normalized":[{"db_name":"MESH","db_id":"D042882"}]},{"id":"21519","type":"Chemical","text":["octreotide"],"offsets":[[377,387]],"normalized":[{"db_name":"MESH","db_id":"D015282"}]},{"id":"21520","type":"Disease","text":["acromegalic"],"offsets":[[396,407]],"normalized":[{"db_name":"MESH","db_id":"D000172"}]},{"id":"21521","type":"Disease","text":["gall stones"],"offsets":[[422,433]],"normalized":[{"db_name":"MESH","db_id":"D042882"}]},{"id":"21522","type":"Disease","text":["gall stones"],"offsets":[[456,467]],"normalized":[{"db_name":"MESH","db_id":"D042882"}]},{"id":"21523","type":"Chemical","text":["cholesterol"],"offsets":[[555,566]],"normalized":[{"db_name":"MESH","db_id":"D002784"}]},{"id":"21524","type":"Chemical","text":["cholesterol"],"offsets":[[773,784]],"normalized":[{"db_name":"MESH","db_id":"D002784"}]},{"id":"21525","type":"Chemical","text":["cholesterol"],"offsets":[[958,969]],"normalized":[{"db_name":"MESH","db_id":"D002784"}]},{"id":"21526","type":"Chemical","text":["cholesterol"],"offsets":[[1050,1061]],"normalized":[{"db_name":"MESH","db_id":"D002784"}]},{"id":"21527","type":"Chemical","text":["cholesterol"],"offsets":[[1151,1162]],"normalized":[{"db_name":"MESH","db_id":"D002784"}]},{"id":"21528","type":"Chemical","text":["ursodeoxycholic acid"],"offsets":[[1244,1264]],"normalized":[{"db_name":"MESH","db_id":"D014580"}]},{"id":"21529","type":"Chemical","text":["UDCA"],"offsets":[[1266,1270]],"normalized":[{"db_name":"MESH","db_id":"D014580"}]},{"id":"21530","type":"Chemical","text":["UDCA"],"offsets":[[1337,1341]],"normalized":[{"db_name":"MESH","db_id":"D014580"}]},{"id":"21531","type":"Disease","text":["gall stone"],"offsets":[[1490,1500]],"normalized":[{"db_name":"MESH","db_id":"D042882"}]},{"id":"21532","type":"Chemical","text":["cholesterol"],"offsets":[[1548,1559]],"normalized":[{"db_name":"MESH","db_id":"D002784"}]},{"id":"21533","type":"Disease","text":["gall stone"],"offsets":[[1634,1644]],"normalized":[{"db_name":"MESH","db_id":"D042882"}]},{"id":"21534","type":"Chemical","text":["octreotide"],"offsets":[[1694,1704]],"normalized":[{"db_name":"MESH","db_id":"D015282"}]},{"id":"21535","type":"Disease","text":["gall stones"],"offsets":[[1713,1724]],"normalized":[{"db_name":"MESH","db_id":"D042882"}]},{"id":"21536","type":"Chemical","text":["cholesterol"],"offsets":[[1760,1771]],"normalized":[{"db_name":"MESH","db_id":"D002784"}]},{"id":"21537","type":"Disease","text":["gall stone disease"],"offsets":[[1814,1832]],"normalized":[{"db_name":"MESH","db_id":"D042882"}]},{"id":"21538","type":"Disease","text":["gall stones"],"offsets":[[1905,1916]],"normalized":[{"db_name":"MESH","db_id":"D042882"}]},{"id":"21539","type":"Chemical","text":["calcium"],"offsets":[[1928,1935]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]}],"events":[],"coreferences":[],"relations":[{"id":"21540","type":"CID","arg1_id":"21514","arg2_id":"21513","normalized":[]},{"id":"21541","type":"CID","arg1_id":"21514","arg2_id":"21518","normalized":[]},{"id":"21542","type":"CID","arg1_id":"21514","arg2_id":"21521","normalized":[]},{"id":"21543","type":"CID","arg1_id":"21514","arg2_id":"21522","normalized":[]},{"id":"21544","type":"CID","arg1_id":"21514","arg2_id":"21531","normalized":[]},{"id":"21545","type":"CID","arg1_id":"21514","arg2_id":"21533","normalized":[]},{"id":"21546","type":"CID","arg1_id":"21514","arg2_id":"21535","normalized":[]},{"id":"21547","type":"CID","arg1_id":"21514","arg2_id":"21537","normalized":[]},{"id":"21548","type":"CID","arg1_id":"21514","arg2_id":"21538","normalized":[]},{"id":"21549","type":"CID","arg1_id":"21516","arg2_id":"21513","normalized":[]},{"id":"21550","type":"CID","arg1_id":"21516","arg2_id":"21518","normalized":[]},{"id":"21551","type":"CID","arg1_id":"21516","arg2_id":"21521","normalized":[]},{"id":"21552","type":"CID","arg1_id":"21516","arg2_id":"21522","normalized":[]},{"id":"21553","type":"CID","arg1_id":"21516","arg2_id":"21531","normalized":[]},{"id":"21554","type":"CID","arg1_id":"21516","arg2_id":"21533","normalized":[]},{"id":"21555","type":"CID","arg1_id":"21516","arg2_id":"21535","normalized":[]},{"id":"21556","type":"CID","arg1_id":"21516","arg2_id":"21537","normalized":[]},{"id":"21557","type":"CID","arg1_id":"21516","arg2_id":"21538","normalized":[]},{"id":"21558","type":"CID","arg1_id":"21519","arg2_id":"21513","normalized":[]},{"id":"21559","type":"CID","arg1_id":"21519","arg2_id":"21518","normalized":[]},{"id":"21560","type":"CID","arg1_id":"21519","arg2_id":"21521","normalized":[]},{"id":"21561","type":"CID","arg1_id":"21519","arg2_id":"21522","normalized":[]},{"id":"21562","type":"CID","arg1_id":"21519","arg2_id":"21531","normalized":[]},{"id":"21563","type":"CID","arg1_id":"21519","arg2_id":"21533","normalized":[]},{"id":"21564","type":"CID","arg1_id":"21519","arg2_id":"21535","normalized":[]},{"id":"21565","type":"CID","arg1_id":"21519","arg2_id":"21537","normalized":[]},{"id":"21566","type":"CID","arg1_id":"21519","arg2_id":"21538","normalized":[]},{"id":"21567","type":"CID","arg1_id":"21534","arg2_id":"21513","normalized":[]},{"id":"21568","type":"CID","arg1_id":"21534","arg2_id":"21518","normalized":[]},{"id":"21569","type":"CID","arg1_id":"21534","arg2_id":"21521","normalized":[]},{"id":"21570","type":"CID","arg1_id":"21534","arg2_id":"21522","normalized":[]},{"id":"21571","type":"CID","arg1_id":"21534","arg2_id":"21531","normalized":[]},{"id":"21572","type":"CID","arg1_id":"21534","arg2_id":"21533","normalized":[]},{"id":"21573","type":"CID","arg1_id":"21534","arg2_id":"21535","normalized":[]},{"id":"21574","type":"CID","arg1_id":"21534","arg2_id":"21537","normalized":[]},{"id":"21575","type":"CID","arg1_id":"21534","arg2_id":"21538","normalized":[]}]}
{"id":"21576","document_id":"7468724","passages":[{"id":"21577","type":"title","text":["Cardiovascular complications associated with terbutaline treatment for preterm labor."],"offsets":[[0,85]]},{"id":"21578","type":"abstract","text":["Severe cardiovascular complications occurred in eight of 160 patients treated with terbutaline for preterm labor. Associated corticosteroid therapy and twin gestations appear to be predisposing factors. Potential mechanisms of the pathophysiology are briefly discussed."],"offsets":[[86,355]]}],"entities":[{"id":"21579","type":"Disease","text":["Cardiovascular complications"],"offsets":[[0,28]],"normalized":[{"db_name":"MESH","db_id":"D002318"}]},{"id":"21580","type":"Chemical","text":["terbutaline"],"offsets":[[45,56]],"normalized":[{"db_name":"MESH","db_id":"D013726"}]},{"id":"21581","type":"Disease","text":["preterm labor"],"offsets":[[71,84]],"normalized":[{"db_name":"MESH","db_id":"D007752"}]},{"id":"21582","type":"Disease","text":["cardiovascular complications"],"offsets":[[93,121]],"normalized":[{"db_name":"MESH","db_id":"D002318"}]},{"id":"21583","type":"Chemical","text":["terbutaline"],"offsets":[[169,180]],"normalized":[{"db_name":"MESH","db_id":"D013726"}]},{"id":"21584","type":"Disease","text":["preterm labor"],"offsets":[[185,198]],"normalized":[{"db_name":"MESH","db_id":"D007752"}]}],"events":[],"coreferences":[],"relations":[{"id":"21585","type":"CID","arg1_id":"21580","arg2_id":"21579","normalized":[]},{"id":"21586","type":"CID","arg1_id":"21580","arg2_id":"21582","normalized":[]},{"id":"21587","type":"CID","arg1_id":"21583","arg2_id":"21579","normalized":[]},{"id":"21588","type":"CID","arg1_id":"21583","arg2_id":"21582","normalized":[]}]}
{"id":"21589","document_id":"7199841","passages":[{"id":"21590","type":"title","text":["Neurologic effects of subarachnoid administration of 2-chloroprocaine-CE, bupivacaine, and low pH normal saline in dogs."],"offsets":[[0,120]]},{"id":"21591","type":"abstract","text":["The purpose of this study was to evaluate the neurologic consequences of deliberate subarachnoid injection of large volumes of 2-chloroprocaine-CE in experimental animals. The possible role of low pH as well as total volume as potential factors in causing neurotoxicity was evaluated. The 65 dogs in the study received injections in the subarachnoid space as follows: 6 to 8 ml of bupivacaine (N = 15), 2-chloroprocaine-CE (N = 20), low pH normal saline (pH 3.0) (N = 20), or normal saline (N = 10). Of the 20 animals that received subarachnoid injection of 2-chloroprocaine-CE seven (35%) developed hind-limb paralysis. None of the animals that received bupivacaine, normal saline, or normal saline titrated to a pH 3.0 developed hind-limb paralysis. Of the 15 spinal cords of the animals that received 2-chloroprocaine-CE, 13 showed subpial necrosis; the nerve roots and subarachnoid vessels were normal. The spinal cords of the animals that received bupivacaine, low pH normal saline (pH 3.0), or normal saline did not show abnormal findings."],"offsets":[[121,1166]]}],"entities":[{"id":"21592","type":"Chemical","text":["2-chloroprocaine-CE"],"offsets":[[53,72]],"normalized":[{"db_name":"MESH","db_id":"C004616"}]},{"id":"21593","type":"Chemical","text":["bupivacaine"],"offsets":[[74,85]],"normalized":[{"db_name":"MESH","db_id":"D002045"}]},{"id":"21594","type":"Chemical","text":["2-chloroprocaine-CE"],"offsets":[[248,267]],"normalized":[{"db_name":"MESH","db_id":"C004616"}]},{"id":"21595","type":"Disease","text":["neurotoxicity"],"offsets":[[377,390]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"21596","type":"Chemical","text":["bupivacaine"],"offsets":[[502,513]],"normalized":[{"db_name":"MESH","db_id":"D002045"}]},{"id":"21597","type":"Chemical","text":["2-chloroprocaine-CE"],"offsets":[[524,543]],"normalized":[{"db_name":"MESH","db_id":"C004616"}]},{"id":"21598","type":"Chemical","text":["2-chloroprocaine-CE"],"offsets":[[679,698]],"normalized":[{"db_name":"MESH","db_id":"C004616"}]},{"id":"21599","type":"Disease","text":["paralysis"],"offsets":[[731,740]],"normalized":[{"db_name":"MESH","db_id":"D010243"}]},{"id":"21600","type":"Chemical","text":["bupivacaine"],"offsets":[[776,787]],"normalized":[{"db_name":"MESH","db_id":"D002045"}]},{"id":"21601","type":"Disease","text":["paralysis"],"offsets":[[862,871]],"normalized":[{"db_name":"MESH","db_id":"D010243"}]},{"id":"21602","type":"Chemical","text":["2-chloroprocaine-CE"],"offsets":[[925,944]],"normalized":[{"db_name":"MESH","db_id":"C004616"}]},{"id":"21603","type":"Disease","text":["subpial necrosis"],"offsets":[[956,972]],"normalized":[{"db_name":"MESH","db_id":"D013118"}]},{"id":"21604","type":"Chemical","text":["bupivacaine"],"offsets":[[1074,1085]],"normalized":[{"db_name":"MESH","db_id":"D002045"}]}],"events":[],"coreferences":[],"relations":[{"id":"21605","type":"CID","arg1_id":"21592","arg2_id":"21599","normalized":[]},{"id":"21606","type":"CID","arg1_id":"21592","arg2_id":"21601","normalized":[]},{"id":"21607","type":"CID","arg1_id":"21594","arg2_id":"21599","normalized":[]},{"id":"21608","type":"CID","arg1_id":"21594","arg2_id":"21601","normalized":[]},{"id":"21609","type":"CID","arg1_id":"21597","arg2_id":"21599","normalized":[]},{"id":"21610","type":"CID","arg1_id":"21597","arg2_id":"21601","normalized":[]},{"id":"21611","type":"CID","arg1_id":"21598","arg2_id":"21599","normalized":[]},{"id":"21612","type":"CID","arg1_id":"21598","arg2_id":"21601","normalized":[]},{"id":"21613","type":"CID","arg1_id":"21602","arg2_id":"21599","normalized":[]},{"id":"21614","type":"CID","arg1_id":"21602","arg2_id":"21601","normalized":[]},{"id":"21615","type":"CID","arg1_id":"21592","arg2_id":"21603","normalized":[]},{"id":"21616","type":"CID","arg1_id":"21594","arg2_id":"21603","normalized":[]},{"id":"21617","type":"CID","arg1_id":"21597","arg2_id":"21603","normalized":[]},{"id":"21618","type":"CID","arg1_id":"21598","arg2_id":"21603","normalized":[]},{"id":"21619","type":"CID","arg1_id":"21602","arg2_id":"21603","normalized":[]}]}
{"id":"21620","document_id":"6640832","passages":[{"id":"21621","type":"title","text":["Early adjuvant adriamycin in superficial bladder carcinoma."],"offsets":[[0,59]]},{"id":"21622","type":"abstract","text":["A multicenter study was performed in 110 patients with superficial transitional cell carcinoma of the bladder. Adriamycin (50 mg\/50 ml) was administered intravesically within 24 h after transurethral resection of TA-T1 (O-A) bladder tumors. Instillation was repeated twice during the first week, then weekly during the first month and afterwards monthly for 1 year. The tolerance was evaluated in these 110 patients, and 29 patients presented with local side-effects. In 24 of these patients chemical cystitis was severe enough for them to drop out of the study. No systemic side-effects were observed. Recurrence was studied in 82 evaluable patients after 1 year of follow-up and in 72 patients followed for 2-3 years (mean 32 months). Of the 82 patients studied after 1 year, 23 had primary and 59 recurrent disease. Of the 82 evaluable patients, 50 did not show any recurrence after 1 year (61%), while 32 presented with one or more recurrences (39%). Of these recurrences, 27 were T1 tumors while five progressed to more highly invasive lesions. In patients that were free of recurrence during the first year, 80% remained tumor-free during the 2- to 3-year follow-up period. Of the patients developing one or more recurrences during the first year, only 50% presented with further recurrence once the instillations were stopped. The beneficial effect of Adriamycin appears obvious and might be related to the drug itself, the early and repeated instillations after TUR, or both."],"offsets":[[60,1543]]}],"entities":[{"id":"21623","type":"Chemical","text":["adriamycin"],"offsets":[[15,25]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"21624","type":"Disease","text":["bladder carcinoma"],"offsets":[[41,58]],"normalized":[{"db_name":"MESH","db_id":"D001749"},{"db_name":"MESH","db_id":"D002277"}]},{"id":"21625","type":"Disease","text":["bladder carcinoma"],"offsets":[[41,58]],"normalized":[{"db_name":"MESH","db_id":"D001749"}]},{"id":"21626","type":"Disease","text":["carcinoma"],"offsets":[[49,58]],"normalized":[{"db_name":"MESH","db_id":"D002277"}]},{"id":"21627","type":"Disease","text":["carcinoma of the bladder"],"offsets":[[145,169]],"normalized":[{"db_name":"MESH","db_id":"D001749"},{"db_name":"MESH","db_id":"D002277"}]},{"id":"21628","type":"Disease","text":["carcinoma of the bladder"],"offsets":[[145,169]],"normalized":[{"db_name":"MESH","db_id":"D001749"}]},{"id":"21629","type":"Disease","text":["carcinoma"],"offsets":[[145,154]],"normalized":[{"db_name":"MESH","db_id":"D002277"}]},{"id":"21630","type":"Chemical","text":["Adriamycin"],"offsets":[[171,181]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"21631","type":"Disease","text":["bladder tumors"],"offsets":[[285,299]],"normalized":[{"db_name":"MESH","db_id":"D001749"}]},{"id":"21632","type":"Disease","text":["cystitis"],"offsets":[[561,569]],"normalized":[{"db_name":"MESH","db_id":"D003556"}]},{"id":"21633","type":"Disease","text":["tumors"],"offsets":[[1048,1054]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"21634","type":"Disease","text":["tumor"],"offsets":[[1187,1192]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"21635","type":"Chemical","text":["Adriamycin"],"offsets":[[1419,1429]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]}],"events":[],"coreferences":[],"relations":[{"id":"21636","type":"CID","arg1_id":"21623","arg2_id":"21632","normalized":[]},{"id":"21637","type":"CID","arg1_id":"21630","arg2_id":"21632","normalized":[]},{"id":"21638","type":"CID","arg1_id":"21635","arg2_id":"21632","normalized":[]}]}
{"id":"21639","document_id":"3560096","passages":[{"id":"21640","type":"title","text":["Hyperkalemia associated with sulindac therapy."],"offsets":[[0,46]]},{"id":"21641","type":"abstract","text":["Hyperkalemia has recently been recognized as a complication of nonsteroidal antiinflammatory agents (NSAID) such as indomethacin. Several recent studies have stressed the renal sparing features of sulindac, owing to its lack of interference with renal prostacyclin synthesis. We describe 4 patients in whom hyperkalemia ranging from 6.1 to 6.9 mEq\/l developed within 3 to 8 days of sulindac administration. In all of them normal serum potassium levels reached within 2 to 4 days of stopping sulindac. As no other medications known to effect serum potassium had been given concomitantly, this course of events is suggestive of a cause-and-effect relationship between sulindac and hyperkalemia. These observations indicate that initial hopes that sulindac may not be associated with the adverse renal effects of other NSAID are probably not justified."],"offsets":[[47,896]]}],"entities":[{"id":"21642","type":"Disease","text":["Hyperkalemia"],"offsets":[[0,12]],"normalized":[{"db_name":"MESH","db_id":"D006947"}]},{"id":"21643","type":"Chemical","text":["sulindac"],"offsets":[[29,37]],"normalized":[{"db_name":"MESH","db_id":"D013467"}]},{"id":"21644","type":"Disease","text":["Hyperkalemia"],"offsets":[[47,59]],"normalized":[{"db_name":"MESH","db_id":"D006947"}]},{"id":"21645","type":"Chemical","text":["indomethacin"],"offsets":[[163,175]],"normalized":[{"db_name":"MESH","db_id":"D007213"}]},{"id":"21646","type":"Chemical","text":["sulindac"],"offsets":[[244,252]],"normalized":[{"db_name":"MESH","db_id":"D013467"}]},{"id":"21647","type":"Chemical","text":["prostacyclin"],"offsets":[[299,311]],"normalized":[{"db_name":"MESH","db_id":"D011464"}]},{"id":"21648","type":"Disease","text":["hyperkalemia"],"offsets":[[354,366]],"normalized":[{"db_name":"MESH","db_id":"D006947"}]},{"id":"21649","type":"Chemical","text":["sulindac"],"offsets":[[429,437]],"normalized":[{"db_name":"MESH","db_id":"D013467"}]},{"id":"21650","type":"Chemical","text":["potassium"],"offsets":[[482,491]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"21651","type":"Chemical","text":["sulindac"],"offsets":[[538,546]],"normalized":[{"db_name":"MESH","db_id":"D013467"}]},{"id":"21652","type":"Chemical","text":["potassium"],"offsets":[[594,603]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"21653","type":"Chemical","text":["sulindac"],"offsets":[[713,721]],"normalized":[{"db_name":"MESH","db_id":"D013467"}]},{"id":"21654","type":"Disease","text":["hyperkalemia"],"offsets":[[726,738]],"normalized":[{"db_name":"MESH","db_id":"D006947"}]},{"id":"21655","type":"Chemical","text":["sulindac"],"offsets":[[792,800]],"normalized":[{"db_name":"MESH","db_id":"D013467"}]}],"events":[],"coreferences":[],"relations":[{"id":"21656","type":"CID","arg1_id":"21645","arg2_id":"21642","normalized":[]},{"id":"21657","type":"CID","arg1_id":"21645","arg2_id":"21644","normalized":[]},{"id":"21658","type":"CID","arg1_id":"21645","arg2_id":"21648","normalized":[]},{"id":"21659","type":"CID","arg1_id":"21645","arg2_id":"21654","normalized":[]},{"id":"21660","type":"CID","arg1_id":"21643","arg2_id":"21642","normalized":[]},{"id":"21661","type":"CID","arg1_id":"21643","arg2_id":"21644","normalized":[]},{"id":"21662","type":"CID","arg1_id":"21643","arg2_id":"21648","normalized":[]},{"id":"21663","type":"CID","arg1_id":"21643","arg2_id":"21654","normalized":[]},{"id":"21664","type":"CID","arg1_id":"21646","arg2_id":"21642","normalized":[]},{"id":"21665","type":"CID","arg1_id":"21646","arg2_id":"21644","normalized":[]},{"id":"21666","type":"CID","arg1_id":"21646","arg2_id":"21648","normalized":[]},{"id":"21667","type":"CID","arg1_id":"21646","arg2_id":"21654","normalized":[]},{"id":"21668","type":"CID","arg1_id":"21649","arg2_id":"21642","normalized":[]},{"id":"21669","type":"CID","arg1_id":"21649","arg2_id":"21644","normalized":[]},{"id":"21670","type":"CID","arg1_id":"21649","arg2_id":"21648","normalized":[]},{"id":"21671","type":"CID","arg1_id":"21649","arg2_id":"21654","normalized":[]},{"id":"21672","type":"CID","arg1_id":"21651","arg2_id":"21642","normalized":[]},{"id":"21673","type":"CID","arg1_id":"21651","arg2_id":"21644","normalized":[]},{"id":"21674","type":"CID","arg1_id":"21651","arg2_id":"21648","normalized":[]},{"id":"21675","type":"CID","arg1_id":"21651","arg2_id":"21654","normalized":[]},{"id":"21676","type":"CID","arg1_id":"21653","arg2_id":"21642","normalized":[]},{"id":"21677","type":"CID","arg1_id":"21653","arg2_id":"21644","normalized":[]},{"id":"21678","type":"CID","arg1_id":"21653","arg2_id":"21648","normalized":[]},{"id":"21679","type":"CID","arg1_id":"21653","arg2_id":"21654","normalized":[]},{"id":"21680","type":"CID","arg1_id":"21655","arg2_id":"21642","normalized":[]},{"id":"21681","type":"CID","arg1_id":"21655","arg2_id":"21644","normalized":[]},{"id":"21682","type":"CID","arg1_id":"21655","arg2_id":"21648","normalized":[]},{"id":"21683","type":"CID","arg1_id":"21655","arg2_id":"21654","normalized":[]}]}
{"id":"21684","document_id":"3358181","passages":[{"id":"21685","type":"title","text":["Ventricular tachyarrhythmias during cesarean section after ritodrine therapy: interaction with anesthetics."],"offsets":[[0,107]]},{"id":"21686","type":"abstract","text":["This case illustrates that patients receiving ritodrine for preterm labor may risk interactions between the residual betamimetic effects of ritodrine and the effects of anesthetics during cesarean section. Such interactions may result in serious cardiovascular complications even after cessation of an infusion of ritodrine. Preoperative assessment should focus on cardiovascular status and serum potassium level. Delaying induction of anesthesia should be considered whenever possible. Careful fluid administration and cautious use of titrated doses of ephedrine are advised. After delivery of the infant, there should be no contraindication to the use of an alpha-adrenergic vasopressor such as phenylephrine to treat hypotensive patients with tachycardia."],"offsets":[[108,866]]}],"entities":[{"id":"21687","type":"Disease","text":["Ventricular tachyarrhythmias"],"offsets":[[0,28]],"normalized":[{"db_name":"MESH","db_id":"D014693"}]},{"id":"21688","type":"Chemical","text":["ritodrine"],"offsets":[[59,68]],"normalized":[{"db_name":"MESH","db_id":"D012312"}]},{"id":"21689","type":"Chemical","text":["ritodrine"],"offsets":[[154,163]],"normalized":[{"db_name":"MESH","db_id":"D012312"}]},{"id":"21690","type":"Disease","text":["preterm labor"],"offsets":[[168,181]],"normalized":[{"db_name":"MESH","db_id":"D007752"}]},{"id":"21691","type":"Chemical","text":["ritodrine"],"offsets":[[248,257]],"normalized":[{"db_name":"MESH","db_id":"D012312"}]},{"id":"21692","type":"Disease","text":["cardiovascular complications"],"offsets":[[354,382]],"normalized":[{"db_name":"MESH","db_id":"D002318"}]},{"id":"21693","type":"Chemical","text":["ritodrine"],"offsets":[[422,431]],"normalized":[{"db_name":"MESH","db_id":"D012312"}]},{"id":"21694","type":"Chemical","text":["potassium"],"offsets":[[505,514]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"21695","type":"Chemical","text":["ephedrine"],"offsets":[[662,671]],"normalized":[{"db_name":"MESH","db_id":"D004809"}]},{"id":"21696","type":"Chemical","text":["phenylephrine"],"offsets":[[805,818]],"normalized":[{"db_name":"MESH","db_id":"D010656"}]},{"id":"21697","type":"Disease","text":["hypotensive"],"offsets":[[828,839]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"21698","type":"Disease","text":["tachycardia"],"offsets":[[854,865]],"normalized":[{"db_name":"MESH","db_id":"D013610"}]}],"events":[],"coreferences":[],"relations":[{"id":"21699","type":"CID","arg1_id":"21688","arg2_id":"21687","normalized":[]},{"id":"21700","type":"CID","arg1_id":"21689","arg2_id":"21687","normalized":[]},{"id":"21701","type":"CID","arg1_id":"21691","arg2_id":"21687","normalized":[]},{"id":"21702","type":"CID","arg1_id":"21693","arg2_id":"21687","normalized":[]}]}
{"id":"21703","document_id":"2887062","passages":[{"id":"21704","type":"title","text":["Immunohistochemical, electron microscopic and morphometric studies of estrogen-induced rat prolactinomas after bromocriptine treatment."],"offsets":[[0,135]]},{"id":"21705","type":"abstract","text":["To clarify the effects of bromocriptine on prolactinoma cells in vivo, immunohistochemical, ultrastructural and morphometrical analyses were applied to estrogen-induced rat prolactinoma cells 1 h and 6 h after injection of bromocriptine (3 mg\/kg of body weight). One h after treatment, serum prolactin levels decreased markedly. Electron microscopy disclosed many secretory granules, slightly distorted rough endoplasmic reticulum, and partially dilated Golgi cisternae in the prolactinoma cells. Morphometric analysis revealed that the volume density of secretory granules increased, while the volume density of cytoplasmic microtubules decreased. These findings suggest that lowered serum prolactin levels in the early phase of bromocriptine treatment may result from an impaired secretion of prolactin due to decreasing numbers of cytoplasmic microtubules. At 6 h after injection, serum prolactin levels were still considerably lower than in controls. The prolactinoma cells at this time were well granulated, with vesiculated rough endoplasmic reticulum and markedly dilated Golgi cisternae. Electron microscopical immunohistochemistry revealed positive reaction products noted on the secretory granules, Golgi cisternae, and endoplasmic reticulum of the untreated rat prolactinoma cells. However, only secretory granules showed the positive reaction products for prolactin 6 h after bromocriptine treatment of the adenoma cells. An increase in the volume density of secretory granules and a decrease in the volume densities of rough endoplasmic reticulum and microtubules was determined by morphometric analysis, suggesting that bromocriptine inhibits protein synthesis as well as bringing about a disturbance of the prolactin secretion."],"offsets":[[136,1878]]}],"entities":[{"id":"21706","type":"Chemical","text":["estrogen"],"offsets":[[70,78]],"normalized":[{"db_name":"MESH","db_id":"D004967"}]},{"id":"21707","type":"Disease","text":["prolactinomas"],"offsets":[[91,104]],"normalized":[{"db_name":"MESH","db_id":"D015175"}]},{"id":"21708","type":"Chemical","text":["bromocriptine"],"offsets":[[111,124]],"normalized":[{"db_name":"MESH","db_id":"D001971"}]},{"id":"21709","type":"Chemical","text":["bromocriptine"],"offsets":[[162,175]],"normalized":[{"db_name":"MESH","db_id":"D001971"}]},{"id":"21710","type":"Disease","text":["prolactinoma"],"offsets":[[179,191]],"normalized":[{"db_name":"MESH","db_id":"D015175"}]},{"id":"21711","type":"Chemical","text":["estrogen"],"offsets":[[288,296]],"normalized":[{"db_name":"MESH","db_id":"D004967"}]},{"id":"21712","type":"Disease","text":["prolactinoma"],"offsets":[[309,321]],"normalized":[{"db_name":"MESH","db_id":"D015175"}]},{"id":"21713","type":"Chemical","text":["bromocriptine"],"offsets":[[359,372]],"normalized":[{"db_name":"MESH","db_id":"D001971"}]},{"id":"21714","type":"Disease","text":["prolactinoma"],"offsets":[[613,625]],"normalized":[{"db_name":"MESH","db_id":"D015175"}]},{"id":"21715","type":"Chemical","text":["bromocriptine"],"offsets":[[866,879]],"normalized":[{"db_name":"MESH","db_id":"D001971"}]},{"id":"21716","type":"Disease","text":["prolactinoma"],"offsets":[[1095,1107]],"normalized":[{"db_name":"MESH","db_id":"D015175"}]},{"id":"21717","type":"Disease","text":["prolactinoma"],"offsets":[[1409,1421]],"normalized":[{"db_name":"MESH","db_id":"D015175"}]},{"id":"21718","type":"Chemical","text":["bromocriptine"],"offsets":[[1524,1537]],"normalized":[{"db_name":"MESH","db_id":"D001971"}]},{"id":"21719","type":"Disease","text":["adenoma"],"offsets":[[1555,1562]],"normalized":[{"db_name":"MESH","db_id":"D000236"}]},{"id":"21720","type":"Chemical","text":["bromocriptine"],"offsets":[[1770,1783]],"normalized":[{"db_name":"MESH","db_id":"D001971"}]}],"events":[],"coreferences":[],"relations":[{"id":"21721","type":"CID","arg1_id":"21706","arg2_id":"21707","normalized":[]},{"id":"21722","type":"CID","arg1_id":"21706","arg2_id":"21710","normalized":[]},{"id":"21723","type":"CID","arg1_id":"21706","arg2_id":"21712","normalized":[]},{"id":"21724","type":"CID","arg1_id":"21706","arg2_id":"21714","normalized":[]},{"id":"21725","type":"CID","arg1_id":"21706","arg2_id":"21716","normalized":[]},{"id":"21726","type":"CID","arg1_id":"21706","arg2_id":"21717","normalized":[]},{"id":"21727","type":"CID","arg1_id":"21711","arg2_id":"21707","normalized":[]},{"id":"21728","type":"CID","arg1_id":"21711","arg2_id":"21710","normalized":[]},{"id":"21729","type":"CID","arg1_id":"21711","arg2_id":"21712","normalized":[]},{"id":"21730","type":"CID","arg1_id":"21711","arg2_id":"21714","normalized":[]},{"id":"21731","type":"CID","arg1_id":"21711","arg2_id":"21716","normalized":[]},{"id":"21732","type":"CID","arg1_id":"21711","arg2_id":"21717","normalized":[]}]}
{"id":"21733","document_id":"2425813","passages":[{"id":"21734","type":"title","text":["On two paradoxical side-effects of prednisolone in rats, ribosomal RNA biosyntheses, and a mechanism of action."],"offsets":[[0,111]]},{"id":"21735","type":"abstract","text":["Liver enlargement and muscle wastage occurred in Wistar rats following the subcutaneous administration of prednisolone. In the liver both the content of RNA and the biosynthesis of ribosomal RNA increased while both the RNA content and ribosomal RNA biosynthesis were reduced in the gastrocnemius muscle. It is suggested that the drug acted in a selective and tissue-specific manner to enhance ribosomal RNA synthesis in the liver and depress such synthesis in the muscle. This view supports the contention that the liver and muscle are independent sites of prednisolone action."],"offsets":[[112,690]]}],"entities":[{"id":"21736","type":"Chemical","text":["prednisolone"],"offsets":[[35,47]],"normalized":[{"db_name":"MESH","db_id":"D011239"}]},{"id":"21737","type":"Disease","text":["Liver enlargement"],"offsets":[[112,129]],"normalized":[{"db_name":"MESH","db_id":"D006529"}]},{"id":"21738","type":"Disease","text":["muscle wastage"],"offsets":[[134,148]],"normalized":[{"db_name":"MESH","db_id":"D009133"}]},{"id":"21739","type":"Chemical","text":["prednisolone"],"offsets":[[218,230]],"normalized":[{"db_name":"MESH","db_id":"D011239"}]},{"id":"21740","type":"Chemical","text":["prednisolone"],"offsets":[[670,682]],"normalized":[{"db_name":"MESH","db_id":"D011239"}]}],"events":[],"coreferences":[],"relations":[{"id":"21741","type":"CID","arg1_id":"21736","arg2_id":"21737","normalized":[]},{"id":"21742","type":"CID","arg1_id":"21739","arg2_id":"21737","normalized":[]},{"id":"21743","type":"CID","arg1_id":"21740","arg2_id":"21737","normalized":[]},{"id":"21744","type":"CID","arg1_id":"21736","arg2_id":"21738","normalized":[]},{"id":"21745","type":"CID","arg1_id":"21739","arg2_id":"21738","normalized":[]},{"id":"21746","type":"CID","arg1_id":"21740","arg2_id":"21738","normalized":[]}]}
{"id":"21747","document_id":"2375138","passages":[{"id":"21748","type":"title","text":["Possible intramuscular midazolam-associated cardiorespiratory arrest and death."],"offsets":[[0,79]]},{"id":"21749","type":"abstract","text":["Midazolam hydrochloride is commonly used for dental or endoscopic procedures. Although generally consisted safe when given intramuscularly, intravenous administration is known to cause respiratory and cardiovascular depression. This report describes the first published case of cardiorespiratory arrest and death associated with intramuscular administration of midazolam. Information regarding midazolam use is reviewed to provide recommendation for safe administration."],"offsets":[[80,550]]}],"entities":[{"id":"21750","type":"Chemical","text":["midazolam"],"offsets":[[23,32]],"normalized":[{"db_name":"MESH","db_id":"D008874"}]},{"id":"21751","type":"Disease","text":["cardiorespiratory arrest"],"offsets":[[44,68]],"normalized":[{"db_name":"MESH","db_id":"D006323"}]},{"id":"21752","type":"Disease","text":["death"],"offsets":[[73,78]],"normalized":[{"db_name":"MESH","db_id":"D003643"}]},{"id":"21753","type":"Chemical","text":["Midazolam hydrochloride"],"offsets":[[80,103]],"normalized":[{"db_name":"MESH","db_id":"D008874"}]},{"id":"21754","type":"Disease","text":["respiratory and cardiovascular depression"],"offsets":[[265,306]],"normalized":[{"db_name":"MESH","db_id":"D012140"},{"db_name":"MESH","db_id":"D002318"}]},{"id":"21755","type":"Disease","text":["respiratory","depression"],"offsets":[[265,276],[296,306]],"normalized":[{"db_name":"MESH","db_id":"D012140"}]},{"id":"21756","type":"Disease","text":["cardiovascular depression"],"offsets":[[281,306]],"normalized":[{"db_name":"MESH","db_id":"D002318"}]},{"id":"21757","type":"Disease","text":["cardiorespiratory arrest"],"offsets":[[358,382]],"normalized":[{"db_name":"MESH","db_id":"D006323"}]},{"id":"21758","type":"Disease","text":["death"],"offsets":[[387,392]],"normalized":[{"db_name":"MESH","db_id":"D003643"}]},{"id":"21759","type":"Chemical","text":["midazolam"],"offsets":[[441,450]],"normalized":[{"db_name":"MESH","db_id":"D008874"}]},{"id":"21760","type":"Chemical","text":["midazolam"],"offsets":[[474,483]],"normalized":[{"db_name":"MESH","db_id":"D008874"}]}],"events":[],"coreferences":[],"relations":[{"id":"21761","type":"CID","arg1_id":"21750","arg2_id":"21754","normalized":[]},{"id":"21762","type":"CID","arg1_id":"21750","arg2_id":"21755","normalized":[]},{"id":"21763","type":"CID","arg1_id":"21753","arg2_id":"21754","normalized":[]},{"id":"21764","type":"CID","arg1_id":"21753","arg2_id":"21755","normalized":[]},{"id":"21765","type":"CID","arg1_id":"21759","arg2_id":"21754","normalized":[]},{"id":"21766","type":"CID","arg1_id":"21759","arg2_id":"21755","normalized":[]},{"id":"21767","type":"CID","arg1_id":"21760","arg2_id":"21754","normalized":[]},{"id":"21768","type":"CID","arg1_id":"21760","arg2_id":"21755","normalized":[]},{"id":"21769","type":"CID","arg1_id":"21750","arg2_id":"21751","normalized":[]},{"id":"21770","type":"CID","arg1_id":"21750","arg2_id":"21757","normalized":[]},{"id":"21771","type":"CID","arg1_id":"21753","arg2_id":"21751","normalized":[]},{"id":"21772","type":"CID","arg1_id":"21753","arg2_id":"21757","normalized":[]},{"id":"21773","type":"CID","arg1_id":"21759","arg2_id":"21751","normalized":[]},{"id":"21774","type":"CID","arg1_id":"21759","arg2_id":"21757","normalized":[]},{"id":"21775","type":"CID","arg1_id":"21760","arg2_id":"21751","normalized":[]},{"id":"21776","type":"CID","arg1_id":"21760","arg2_id":"21757","normalized":[]}]}
{"id":"21777","document_id":"2265898","passages":[{"id":"21778","type":"title","text":["Serial epilepsy caused by levodopa\/carbidopa administration in two patients on hemodialysis."],"offsets":[[0,92]]},{"id":"21779","type":"abstract","text":["Two patients with similar clinical features are presented: both patients had chronic renal failure, on hemodialysis for many years but recently begun on a high-flux dialyzer; both had been receiving a carbidopa\/levodopa preparation; and both had the onset of hallucinosis and recurrent seizures, which were refractory to anticonvulsants. The first patient died without a diagnosis; the second patient had a dramatic recovery following the administration of vitamin B6. Neither patient was considered to have a renal state sufficiently severe enough to explain their presentation."],"offsets":[[93,672]]}],"entities":[{"id":"21780","type":"Disease","text":["epilepsy"],"offsets":[[7,15]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"21781","type":"Chemical","text":["levodopa\/carbidopa"],"offsets":[[26,44]],"normalized":[{"db_name":"MESH","db_id":"C009265"}]},{"id":"21782","type":"Disease","text":["chronic renal failure"],"offsets":[[170,191]],"normalized":[{"db_name":"MESH","db_id":"D007676"}]},{"id":"21783","type":"Chemical","text":["carbidopa\/levodopa"],"offsets":[[294,312]],"normalized":[{"db_name":"MESH","db_id":"C009265"}]},{"id":"21784","type":"Disease","text":["hallucinosis"],"offsets":[[352,364]],"normalized":[{"db_name":"MESH","db_id":"D001523"}]},{"id":"21785","type":"Disease","text":["seizures"],"offsets":[[379,387]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"21786","type":"Chemical","text":["vitamin B6"],"offsets":[[550,560]],"normalized":[{"db_name":"MESH","db_id":"D025101"}]}],"events":[],"coreferences":[],"relations":[{"id":"21787","type":"CID","arg1_id":"21781","arg2_id":"21780","normalized":[]},{"id":"21788","type":"CID","arg1_id":"21783","arg2_id":"21780","normalized":[]}]}
{"id":"21789","document_id":"2071257","passages":[{"id":"21790","type":"title","text":["Effect of L-alpha-glyceryl-phosphorylcholine on amnesia caused by scopolamine."],"offsets":[[0,78]]},{"id":"21791","type":"abstract","text":["The present study was carried out to test the effects of L-alpha-glycerylphosphorylcholine (L-alpha-GFC) on memory impairment induced by scopolamine in man. Thirty-two healthy young volunteers were randomly allocated to four different groups. They were given a ten day pretreatment with either L-alpha-GFC or placebo, p.o., and on the eleventh day either scopolamine or placebo, i.m. Before and 0.5, 1, 2, 3, and 6 h after injection the subjects were given attention and mnemonic tests. The findings of this study indicate that the drug is able to antagonize impairment of attention and memory induced by scopolamine."],"offsets":[[79,696]]}],"entities":[{"id":"21792","type":"Chemical","text":["L-alpha-glyceryl-phosphorylcholine"],"offsets":[[10,44]],"normalized":[{"db_name":"MESH","db_id":"D005997"}]},{"id":"21793","type":"Disease","text":["amnesia"],"offsets":[[48,55]],"normalized":[{"db_name":"MESH","db_id":"D000647"}]},{"id":"21794","type":"Chemical","text":["scopolamine"],"offsets":[[66,77]],"normalized":[{"db_name":"MESH","db_id":"D012601"}]},{"id":"21795","type":"Chemical","text":["L-alpha-glycerylphosphorylcholine"],"offsets":[[136,169]],"normalized":[{"db_name":"MESH","db_id":"D005997"}]},{"id":"21796","type":"Chemical","text":["L-alpha-GFC"],"offsets":[[171,182]],"normalized":[{"db_name":"MESH","db_id":"D005997"}]},{"id":"21797","type":"Disease","text":["memory impairment"],"offsets":[[187,204]],"normalized":[{"db_name":"MESH","db_id":"D008569"}]},{"id":"21798","type":"Chemical","text":["scopolamine"],"offsets":[[216,227]],"normalized":[{"db_name":"MESH","db_id":"D012601"}]},{"id":"21799","type":"Chemical","text":["L-alpha-GFC"],"offsets":[[373,384]],"normalized":[{"db_name":"MESH","db_id":"D005997"}]},{"id":"21800","type":"Chemical","text":["scopolamine"],"offsets":[[434,445]],"normalized":[{"db_name":"MESH","db_id":"D012601"}]},{"id":"21801","type":"Disease","text":["impairment of attention and memory"],"offsets":[[638,672]],"normalized":[{"db_name":"MESH","db_id":"D008569"}]},{"id":"21802","type":"Chemical","text":["scopolamine"],"offsets":[[684,695]],"normalized":[{"db_name":"MESH","db_id":"D012601"}]}],"events":[],"coreferences":[],"relations":[{"id":"21803","type":"CID","arg1_id":"21794","arg2_id":"21797","normalized":[]},{"id":"21804","type":"CID","arg1_id":"21794","arg2_id":"21801","normalized":[]},{"id":"21805","type":"CID","arg1_id":"21798","arg2_id":"21797","normalized":[]},{"id":"21806","type":"CID","arg1_id":"21798","arg2_id":"21801","normalized":[]},{"id":"21807","type":"CID","arg1_id":"21800","arg2_id":"21797","normalized":[]},{"id":"21808","type":"CID","arg1_id":"21800","arg2_id":"21801","normalized":[]},{"id":"21809","type":"CID","arg1_id":"21802","arg2_id":"21797","normalized":[]},{"id":"21810","type":"CID","arg1_id":"21802","arg2_id":"21801","normalized":[]}]}
{"id":"21811","document_id":"1592014","passages":[{"id":"21812","type":"title","text":["Seizures induced by the cocaine metabolite benzoylecgonine in rats."],"offsets":[[0,67]]},{"id":"21813","type":"abstract","text":["The half-life (t1\/2) of cocaine is relatively short, but some of the consequences of its use, such as seizures and strokes, can occur hours after exposure. This led us to hypothesize that a metabolite of cocaine may be responsible for some of those delayed sequelae. We evaluated the potential of the major metabolite of cocaine, benzoylecgonine (BE), to cause seizures. Two separate equimolar doses (0.2 and 0.4 mumol) of either cocaine or BE were injected ventricularly in unanesthetized juvenile rats. Treated rats were then evaluated for incidence, latency, and seizure pattern or for locomotor activity in animals without seizures. BE-Induced seizures occurred more frequently and had significantly longer latencies than those induced by equimolar amounts of cocaine. Whereas cocaine-induced seizures were best characterized as brief, generalized, and tonic and resulted in death, those induced by BE were prolonged, often multiple and mixed in type, and rarely resulted in death. Electrical recordings from the hippocampus showed a rhythmic progression in EEG frequency and voltage with clinical seizure expression. BE-Injected rats that did not have seizures had significantly more locomotor activity than cocaine-injected animals without seizures. The finding that cocaine- and BE-induced seizures differ in several respects suggests more than one mechanism for cocaine-induced seizures and emphasizes the importance of a cocaine metabolite, 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{"id":"22089","document_id":"1436384","passages":[{"id":"22090","type":"title","text":["Protection against amphetamine-induced neurotoxicity toward striatal dopamine neurons in rodents by LY274614, an excitatory amino acid antagonist."],"offsets":[[0,146]]},{"id":"22091","type":"abstract","text":["LY274614, 3SR,4aRS,6SR,8aRS-6-[phosphonomethyl]decahydr oisoquinoline-3- carboxylic acid, has been described as a potent antagonist of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor. Here its ability to antagonize the prolonged depletion of dopamine in the striatum by amphetamine in iprindole-treated rats is reported. A single 18.4 mg\/kg (i.p.) dose of (+\/-)-amphetamine hemisulfate, given to rats pretreated with iprindole, resulted in persistent depletion of dopamine in the striatum 1 week later. This prolonged depletion of dopamine in the striatum was antagonized by dizocilpine (MK-801, a non-competitive antagonist of NMDA receptors) or by LY274614 (a competitive antagonist of NMDA receptors). The protective effect of LY274614 was dose-dependent, being maximum at 10-40 mgkg (i.p.). A 10 mg\/kg dose of LY274614 was effective in antagonizing the depletion of dopamine in the striatum, when given as long as 8 hr prior to amphetamine but not when given 24 hr prior to amphetamine. Depletion of dopamine in the striatum was also antagonized when LY274614 was given after the injection of amphetamine; LY274614 protected when given up to 4 hr after but not when given 8 or 24 hr after amphetamine. The prolonged depletion of dopamine in the striatum in mice, given multiple injections of methamphetamine, was also antagonized dose-dependently and completely by LY274614. The data strengthen the evidence that the neurotoxic effect of amphetamine and related compounds toward nigrostriatal dopamine neurons involves NMDA receptors and that LY274614 is an NMDA receptor antagonist with long-lasting in vivo effects in rats."],"offsets":[[147,1790]]}],"entities":[{"id":"22092","type":"Chemical","text":["amphetamine"],"offsets":[[19,30]],"normalized":[{"db_name":"MESH","db_id":"D000661"}]},{"id":"22093","type":"Disease","text":["neurotoxicity"],"offsets":[[39,52]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"22094","type":"Chemical","text":["dopamine"],"offsets":[[69,77]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"22095","type":"Chemical","text":["LY274614"],"offsets":[[100,108]],"normalized":[{"db_name":"MESH","db_id":"C070935"}]},{"id":"22096","type":"Chemical","text":["amino 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{"id":"22149","document_id":"1085609","passages":[{"id":"22150","type":"title","text":["Neonatal pyridoxine responsive convulsions due to isoniazid therapy."],"offsets":[[0,68]]},{"id":"22151","type":"abstract","text":["A 17-day-old infant on isoniazid therapy 13 mg\/kg daily from birth because of maternal tuberculosis was admitted after 4 days of clonic fits. No underlying infective or biochemical cause could be found. The fits ceased within 4 hours of administering intramuscular pyridoxine, suggesting an aetiology of pyridoxine deficiency secondary to isoniazid medication."],"offsets":[[69,429]]}],"entities":[{"id":"22152","type":"Chemical","text":["pyridoxine"],"offsets":[[9,19]],"normalized":[{"db_name":"MESH","db_id":"D011736"}]},{"id":"22153","type":"Disease","text":["convulsions"],"offsets":[[31,42]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"22154","type":"Chemical","text":["isoniazid"],"offsets":[[50,59]],"normalized":[{"db_name":"MESH","db_id":"D007538"}]},{"id":"22155","type":"Chemical","text":["isoniazid"],"offsets":[[92,101]],"normalized":[{"db_name":"MESH","db_id":"D007538"}]},{"id":"22156","type":"Disease","text":["tuberculosis"],"offsets":[[156,168]],"normalized":[{"db_name":"MESH","db_id":"D014376"}]},{"id":"22157","type":"Disease","text":["clonic fits"],"offsets":[[198,209]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"22158","type":"Disease","text":["fits"],"offsets":[[276,280]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"22159","type":"Chemical","text":["pyridoxine"],"offsets":[[334,344]],"normalized":[{"db_name":"MESH","db_id":"D011736"}]},{"id":"22160","type":"Chemical","text":["pyridoxine"],"offsets":[[373,383]],"normalized":[{"db_name":"MESH","db_id":"D011736"}]},{"id":"22161","type":"Chemical","text":["isoniazid"],"offsets":[[408,417]],"normalized":[{"db_name":"MESH","db_id":"D007538"}]}],"events":[],"coreferences":[],"relations":[{"id":"22162","type":"CID","arg1_id":"22154","arg2_id":"22153","normalized":[]},{"id":"22163","type":"CID","arg1_id":"22154","arg2_id":"22157","normalized":[]},{"id":"22164","type":"CID","arg1_id":"22154","arg2_id":"22158","normalized":[]},{"id":"22165","type":"CID","arg1_id":"22155","arg2_id":"22153","normalized":[]},{"id":"22166","type":"CID","arg1_id":"22155","arg2_id":"22157","normalized":[]},{"id":"22167","type":"CID","arg1_id":"22155","arg2_id":"22158","normalized":[]},{"id":"22168","type":"CID","arg1_id":"22161","arg2_id":"22153","normalized":[]},{"id":"22169","type":"CID","arg1_id":"22161","arg2_id":"22157","normalized":[]},{"id":"22170","type":"CID","arg1_id":"22161","arg2_id":"22158","normalized":[]}]}
{"id":"22171","document_id":"809711","passages":[{"id":"22172","type":"title","text":["Reversal by phenylephrine of the beneficial effects of intravenous nitroglycerin in patients with acute myocardial infarction."],"offsets":[[0,126]]},{"id":"22173","type":"abstract","text":["Nitroglycerin has been shown to reduce ST-segment elevation during acute myocardial infarction, an effect potentiated in the dog by agents that reverse nitroglycerin-induced hypotension. Our study was designed to determine the effects of combined nitroglycerin and phenylephrine therapy. Ten patients with acute transmural myocardial infarctions received intravenous nitroglycerin, sufficient to reduce mean arterial pressure from 107 +\/- 6 to 85 +\/- 6 mm Hg (P less than 0.001), for 60 minutes. Left ventricular filling pressure decreased from 19 +\/- 2 to 11 +\/- 2 mm Hg (P less than 0.001). SigmaST, the sum of ST-segment elevations in 16 precordial leads, decreased (P less than 0.02) with intravenous nitroglycerin. Subsequent addition of phenylephrine infusion, sufficient to re-elevate mean arterial pressure to 106 +\/- 4 mm Hg (P less than 0.001) for 30 minutes, increased left ventricular filling pressure to 17 +\/- 2 mm Hg (P less than 0.05) and also significantly increased sigmaST (P less than 0.05). Our results suggest that addition of phenylephrine to nitroglycerin is not beneficial in the treatment of patients with acute myocardial infarction."],"offsets":[[127,1287]]}],"entities":[{"id":"22174","type":"Chemical","text":["phenylephrine"],"offsets":[[12,25]],"normalized":[{"db_name":"MESH","db_id":"D010656"}]},{"id":"22175","type":"Chemical","text":["nitroglycerin"],"offsets":[[67,80]],"normalized":[{"db_name":"MESH","db_id":"D005996"}]},{"id":"22176","type":"Disease","text":["acute myocardial infarction"],"offsets":[[98,125]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"22177","type":"Chemical","text":["Nitroglycerin"],"offsets":[[127,140]],"normalized":[{"db_name":"MESH","db_id":"D005996"}]},{"id":"22178","type":"Disease","text":["acute myocardial infarction"],"offsets":[[194,221]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"22179","type":"Chemical","text":["nitroglycerin"],"offsets":[[279,292]],"normalized":[{"db_name":"MESH","db_id":"D005996"}]},{"id":"22180","type":"Disease","text":["hypotension"],"offsets":[[301,312]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"22181","type":"Chemical","text":["nitroglycerin"],"offsets":[[374,387]],"normalized":[{"db_name":"MESH","db_id":"D005996"}]},{"id":"22182","type":"Chemical","text":["phenylephrine"],"offsets":[[392,405]],"normalized":[{"db_name":"MESH","db_id":"D010656"}]},{"id":"22183","type":"Disease","text":["myocardial infarctions"],"offsets":[[450,472]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"22184","type":"Chemical","text":["nitroglycerin"],"offsets":[[494,507]],"normalized":[{"db_name":"MESH","db_id":"D005996"}]},{"id":"22185","type":"Chemical","text":["nitroglycerin"],"offsets":[[832,845]],"normalized":[{"db_name":"MESH","db_id":"D005996"}]},{"id":"22186","type":"Chemical","text":["phenylephrine"],"offsets":[[870,883]],"normalized":[{"db_name":"MESH","db_id":"D010656"}]},{"id":"22187","type":"Chemical","text":["phenylephrine"],"offsets":[[1176,1189]],"normalized":[{"db_name":"MESH","db_id":"D010656"}]},{"id":"22188","type":"Chemical","text":["nitroglycerin"],"offsets":[[1193,1206]],"normalized":[{"db_name":"MESH","db_id":"D005996"}]},{"id":"22189","type":"Disease","text":["acute myocardial infarction"],"offsets":[[1259,1286]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]}],"events":[],"coreferences":[],"relations":[{"id":"22190","type":"CID","arg1_id":"22175","arg2_id":"22180","normalized":[]},{"id":"22191","type":"CID","arg1_id":"22177","arg2_id":"22180","normalized":[]},{"id":"22192","type":"CID","arg1_id":"22179","arg2_id":"22180","normalized":[]},{"id":"22193","type":"CID","arg1_id":"22181","arg2_id":"22180","normalized":[]},{"id":"22194","type":"CID","arg1_id":"22184","arg2_id":"22180","normalized":[]},{"id":"22195","type":"CID","arg1_id":"22185","arg2_id":"22180","normalized":[]},{"id":"22196","type":"CID","arg1_id":"22188","arg2_id":"22180","normalized":[]}]}
{"id":"22197","document_id":"20621845","passages":[{"id":"22198","type":"title","text":["Elevation of ADAM10, ADAM17, MMP-2 and MMP-9 expression with media degeneration features CaCl2-induced thoracic aortic aneurysm in a rat model."],"offsets":[[0,143]]},{"id":"22199","type":"abstract","text":["PURPOSE: This study was designed to establish a rat model of thoracic aortic aneurysm (TAA) by calcium chloride (CaCl(2))-induced arterial injury and to explore the potential role of a disintegrin and metalloproteinase (ADAM), matrix metalloproteinases (MMPs) and their endogenous inhibitors (TIMPs) in TAA formation. METHODS: Thoracic aorta of male Sprague-Dawley rats was exposed to 0.5M CaCl(2) or normal saline (NaCl). After 12weeks, animals were euthanized, and CaCl(2)-treated, CaCl(2)-untreated (n=12) and NaCl-treated aortic segments (n=12) were collected for histological and molecular assessments. MMP-TIMP and ADAM mRNAs were semi-quantitatively analyzed and protein expressions were determined by immunohistochemistry. RESULTS: Despite similar external diameters among CaCl(2)-treated, non-CaCl(2)-treated and NaCl-treated segments, aneurymal alteration (n=6, 50%), media degeneration with regional disruption, fragmentation of elastic fiber, and increased collagen deposition (n=12, 100%) were demonstrated in CaCl(2)-treated segments. MMP-2, MMP-9, ADAM-10 and ADAM-17 mRNA levels were increased in CaCl(2)-treated segments (all p<0.01), with trends of elevation in CaCl(2)-untreated segments, as compared with NaCl-treated segments. Immunohistochemistry displayed significantly increased expressions of MMP-2, MMP-9, ADAM-10 and ADAM-17 (all p<0.01) in intima and media for CaCl(2)-treated segments. TIMP mRNA and tissue levels did not differ obviously among the three aortic segments. CONCLUSION: This study establishes a TAA model by periarterial CaCl(2) exposure in rats, and demonstrates a significant elevation of expression of MMP-2, MMP-9, ADAM10 and ADAM17 in the pathogenesis of vascular remodeling."],"offsets":[[144,1867]]}],"entities":[{"id":"22200","type":"Chemical","text":["CaCl2"],"offsets":[[89,94]],"normalized":[{"db_name":"MESH","db_id":"D002122"}]},{"id":"22201","type":"Disease","text":["thoracic aortic aneurysm"],"offsets":[[103,127]],"normalized":[{"db_name":"MESH","db_id":"D017545"}]},{"id":"22202","type":"Disease","text":["thoracic aortic aneurysm"],"offsets":[[205,229]],"normalized":[{"db_name":"MESH","db_id":"D017545"}]},{"id":"22203","type":"Disease","text":["TAA"],"offsets":[[231,234]],"normalized":[{"db_name":"MESH","db_id":"D017545"}]},{"id":"22204","type":"Chemical","text":["calcium 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{"id":"22288","document_id":"19843802","passages":[{"id":"22289","type":"title","text":["When drugs disappear from the patient: elimination of intravenous medication by hemodiafiltration."],"offsets":[[0,98]]},{"id":"22290","type":"abstract","text":["Twenty-three hours after heart transplantation, life-threatening acute right heart failure was diagnosed in a patient requiring continuous venovenous hemodiafiltration (CVVHDF). Increasing doses of catecholamines, sedatives, and muscle relaxants administered through a central venous catheter were ineffective. However, a bolus of epinephrine injected through an alternative catheter provoked a hypertensive crisis. Thus, interference with the central venous infusion by the dialysis catheter was suspected. The catheters were changed, and hemodynamics stabilized at lower catecholamine doses. When the effects of IV drugs are inadequate in patients receiving CVVHDF, interference with adjacent catheters resulting in elimination of the drug by CVVHDF should be suspected."],"offsets":[[99,871]]}],"entities":[{"id":"22291","type":"Disease","text":["right heart failure"],"offsets":[[170,189]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]},{"id":"22292","type":"Chemical","text":["catecholamines"],"offsets":[[297,311]],"normalized":[{"db_name":"MESH","db_id":"D002395"}]},{"id":"22293","type":"Chemical","text":["epinephrine"],"offsets":[[430,441]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"22294","type":"Disease","text":["hypertensive"],"offsets":[[494,506]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"22295","type":"Chemical","text":["catecholamine"],"offsets":[[672,685]],"normalized":[{"db_name":"MESH","db_id":"D002395"}]}],"events":[],"coreferences":[],"relations":[{"id":"22296","type":"CID","arg1_id":"22293","arg2_id":"22294","normalized":[]}]}
{"id":"22297","document_id":"19473225","passages":[{"id":"22298","type":"title","text":["Long-term glutamate supplementation failed to protect against peripheral neurotoxicity of paclitaxel."],"offsets":[[0,101]]},{"id":"22299","type":"abstract","text":["Toxic peripheral neuropathy is still a significant limiting factor for chemotherapy with paclitaxel (PAC), although glutamate and its closely related amino acid glutamine were claimed to ameliorate PAC neurotoxicity. This pilot trial aimed to evaluate the role of glutamate supplementation for preventing PAC-induced peripheral neuropathy in a randomized, placebo-controlled, double-blinded clinical and electro-diagnostic study. Forty-three ovarian cancer patients were available for analysis following six cycles of the same PAC-containing regimen: 23 had been supplemented by glutamate all along the treatment period, at a daily dose of three times 500 mg (group G), and 20 had received a placebo (group P). Patients were evaluated by neurological examinations, questionnaires and sensory-motor nerve conduction studies. There was no significant difference in the frequency of signs or symptoms between the two groups although neurotoxicity symptoms presented mostly with lower scores of severity in group G. However, this difference reached statistical significance only with regard to reported pain sensation (P = 0.011). Also the frequency of abnormal electro-diagnostic findings showed similarity between the two groups (G: 7\/23 = 30.4%; P: 6\/20 = 30%). This pilot study leads to the conclusion that glutamate supplementation at the chosen regimen fails to protect against peripheral neurotoxicity of PAC."],"offsets":[[102,1514]]}],"entities":[{"id":"22300","type":"Chemical","text":["glutamate"],"offsets":[[10,19]],"normalized":[{"db_name":"MESH","db_id":"D018698"}]},{"id":"22301","type":"Disease","text":["peripheral neurotoxicity"],"offsets":[[62,86]],"normalized":[{"db_name":"MESH","db_id":"D010523"}]},{"id":"22302","type":"Chemical","text":["paclitaxel"],"offsets":[[90,100]],"normalized":[{"db_name":"MESH","db_id":"D017239"}]},{"id":"22303","type":"Disease","text":["peripheral 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{"id":"22350","document_id":"19387625","passages":[{"id":"22351","type":"title","text":["Attentional modulation of perceived pain intensity in capsaicin-induced secondary hyperalgesia."],"offsets":[[0,95]]},{"id":"22352","type":"abstract","text":["Perceived pain intensity is modulated by attention. However, it is not known that how pain intensity ratings are affected by attention in capsaicin-induced secondary hyperalgesia. Here we show that perceived pain intensity in secondary hyperalgesia is decreased when attention is distracted away from the painful pinprick stimulus with a visual task. Furthermore, it was found that the magnitude of attentional modulation in secondary hyperalgesia is very similar to that of capsaicin-untreated, control condition. Our findings, showing no interaction between capsaicin treatment and attentional modulation suggest that capsaicin-induced secondary hyperalgesia and attention might affect mechanical pain through independent mechanisms."],"offsets":[[96,831]]}],"entities":[{"id":"22353","type":"Disease","text":["pain"],"offsets":[[36,40]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"22354","type":"Chemical","text":["capsaicin"],"offsets":[[54,63]],"normalized":[{"db_name":"MESH","db_id":"D002211"}]},{"id":"22355","type":"Disease","text":["hyperalgesia"],"offsets":[[82,94]],"normalized":[{"db_name":"MESH","db_id":"D006930"}]},{"id":"22356","type":"Disease","text":["pain"],"offsets":[[106,110]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"22357","type":"Disease","text":["pain"],"offsets":[[182,186]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"22358","type":"Chemical","text":["capsaicin"],"offsets":[[234,243]],"normalized":[{"db_name":"MESH","db_id":"D002211"}]},{"id":"22359","type":"Disease","text":["hyperalgesia"],"offsets":[[262,274]],"normalized":[{"db_name":"MESH","db_id":"D006930"}]},{"id":"22360","type":"Disease","text":["pain"],"offsets":[[304,308]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"22361","type":"Disease","text":["hyperalgesia"],"offsets":[[332,344]],"normalized":[{"db_name":"MESH","db_id":"D006930"}]},{"id":"22362","type":"Disease","text":["hyperalgesia"],"offsets":[[531,543]],"normalized":[{"db_name":"MESH","db_id":"D006930"}]},{"id":"22363","type":"Chemical","text":["capsaicin"],"offsets":[[571,580]],"normalized":[{"db_name":"MESH","db_id":"D002211"}]},{"id":"22364","type":"Chemical","text":["capsaicin"],"offsets":[[656,665]],"normalized":[{"db_name":"MESH","db_id":"D002211"}]},{"id":"22365","type":"Chemical","text":["capsaicin"],"offsets":[[716,725]],"normalized":[{"db_name":"MESH","db_id":"D002211"}]},{"id":"22366","type":"Disease","text":["hyperalgesia"],"offsets":[[744,756]],"normalized":[{"db_name":"MESH","db_id":"D006930"}]},{"id":"22367","type":"Disease","text":["pain"],"offsets":[[795,799]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]}],"events":[],"coreferences":[],"relations":[{"id":"22368","type":"CID","arg1_id":"22354","arg2_id":"22355","normalized":[]},{"id":"22369","type":"CID","arg1_id":"22354","arg2_id":"22359","normalized":[]},{"id":"22370","type":"CID","arg1_id":"22354","arg2_id":"22361","normalized":[]},{"id":"22371","type":"CID","arg1_id":"22354","arg2_id":"22362","normalized":[]},{"id":"22372","type":"CID","arg1_id":"22354","arg2_id":"22366","normalized":[]},{"id":"22373","type":"CID","arg1_id":"22358","arg2_id":"22355","normalized":[]},{"id":"22374","type":"CID","arg1_id":"22358","arg2_id":"22359","normalized":[]},{"id":"22375","type":"CID","arg1_id":"22358","arg2_id":"22361","normalized":[]},{"id":"22376","type":"CID","arg1_id":"22358","arg2_id":"22362","normalized":[]},{"id":"22377","type":"CID","arg1_id":"22358","arg2_id":"22366","normalized":[]},{"id":"22378","type":"CID","arg1_id":"22363","arg2_id":"22355","normalized":[]},{"id":"22379","type":"CID","arg1_id":"22363","arg2_id":"22359","normalized":[]},{"id":"22380","type":"CID","arg1_id":"22363","arg2_id":"22361","normalized":[]},{"id":"22381","type":"CID","arg1_id":"22363","arg2_id":"22362","normalized":[]},{"id":"22382","type":"CID","arg1_id":"22363","arg2_id":"22366","normalized":[]},{"id":"22383","type":"CID","arg1_id":"22364","arg2_id":"22355","normalized":[]},{"id":"22384","type":"CID","arg1_id":"22364","arg2_id":"22359","normalized":[]},{"id":"22385","type":"CID","arg1_id":"22364","arg2_id":"22361","normalized":[]},{"id":"22386","type":"CID","arg1_id":"22364","arg2_id":"22362","normalized":[]},{"id":"22387","type":"CID","arg1_id":"22364","arg2_id":"22366","normalized":[]},{"id":"22388","type":"CID","arg1_id":"22365","arg2_id":"22355","normalized":[]},{"id":"22389","type":"CID","arg1_id":"22365","arg2_id":"22359","normalized":[]},{"id":"22390","type":"CID","arg1_id":"22365","arg2_id":"22361","normalized":[]},{"id":"22391","type":"CID","arg1_id":"22365","arg2_id":"22362","normalized":[]},{"id":"22392","type":"CID","arg1_id":"22365","arg2_id":"22366","normalized":[]}]}
{"id":"22393","document_id":"19211690","passages":[{"id":"22394","type":"title","text":["Testosterone-dependent hypertension and upregulation of intrarenal angiotensinogen in Dahl salt-sensitive rats."],"offsets":[[0,111]]},{"id":"22395","type":"abstract","text":["Blood pressure (BP) is more salt sensitive in men than in premenopausal women. In Dahl salt-sensitive rats (DS), high-salt (HS) diet increases BP more in males than females. In contrast to the systemic renin-angiotensin system, which is suppressed in response to HS in male DS, intrarenal angiotensinogen expression is increased, and intrarenal levels of ANG II are not suppressed. In this study, the hypothesis was tested that there is a sexual dimorphism in HS-induced upregulation of intrarenal angiotensinogen mediated by testosterone that also causes increases in BP and renal injury. On a low-salt (LS) diet, male DS had higher levels of intrarenal angiotensinogen mRNA than females. HS diet for 4 wk increased renal cortical angiotensinogen mRNA and protein only in male DS, which was prevented by castration. Ovariectomy of female DS had no effect on intrarenal angiotensinogen expression on either diet. Radiotelemetric BP was similar between males and castrated rats on LS diet. HS diet for 4 wk caused a progressive increase in BP, protein and albumin excretion, and glomerular sclerosis in male DS rats, which were attenuated by castration. Testosterone replacement in castrated DS rats increased BP, renal injury, and upregulation of renal angiotensinogen associated with HS diet. Testosterone contributes to the development of hypertension and renal injury in male DS rats on HS diet possibly through upregulation of the intrarenal renin-angiotensin system."],"offsets":[[112,1583]]}],"entities":[{"id":"22396","type":"Chemical","text":["Testosterone"],"offsets":[[0,12]],"normalized":[{"db_name":"MESH","db_id":"D013739"}]},{"id":"22397","type":"Disease","text":["hypertension"],"offsets":[[23,35]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"22398","type":"Chemical","text":["salt"],"offsets":[[91,95]],"normalized":[{"db_name":"MESH","db_id":"D017673"}]},{"id":"22399","type":"Chemical","text":["salt"],"offsets":[[140,144]],"normalized":[{"db_name":"MESH","db_id":"D017673"}]},{"id":"22400","type":"Chemical","text":["salt"],"offsets":[[199,203]],"normalized":[{"db_name":"MESH","db_id":"D017673"}]},{"id":"22401","type":"Chemical","text":["salt"],"offsets":[[230,234]],"normalized":[{"db_name":"MESH","db_id":"D017673"}]},{"id":"22402","type":"Chemical","text":["angiotensin"],"offsets":[[320,331]],"normalized":[{"db_name":"MESH","db_id":"D000809"}]},{"id":"22403","type":"Chemical","text":["testosterone"],"offsets":[[638,650]],"normalized":[{"db_name":"MESH","db_id":"D013739"}]},{"id":"22404","type":"Disease","text":["renal injury"],"offsets":[[688,700]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"22405","type":"Chemical","text":["salt"],"offsets":[[711,715]],"normalized":[{"db_name":"MESH","db_id":"D017673"}]},{"id":"22406","type":"Disease","text":["glomerular sclerosis"],"offsets":[[1190,1210]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"22407","type":"Chemical","text":["Testosterone"],"offsets":[[1265,1277]],"normalized":[{"db_name":"MESH","db_id":"D013739"}]},{"id":"22408","type":"Disease","text":["renal injury"],"offsets":[[1325,1337]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"22409","type":"Chemical","text":["Testosterone"],"offsets":[[1406,1418]],"normalized":[{"db_name":"MESH","db_id":"D013739"}]},{"id":"22410","type":"Disease","text":["hypertension"],"offsets":[[1453,1465]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"22411","type":"Disease","text":["renal injury"],"offsets":[[1470,1482]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"22412","type":"Chemical","text":["angiotensin"],"offsets":[[1564,1575]],"normalized":[{"db_name":"MESH","db_id":"D000809"}]}],"events":[],"coreferences":[],"relations":[{"id":"22413","type":"CID","arg1_id":"22398","arg2_id":"22404","normalized":[]},{"id":"22414","type":"CID","arg1_id":"22398","arg2_id":"22406","normalized":[]},{"id":"22415","type":"CID","arg1_id":"22398","arg2_id":"22408","normalized":[]},{"id":"22416","type":"CID","arg1_id":"22398","arg2_id":"22411","normalized":[]},{"id":"22417","type":"CID","arg1_id":"22399","arg2_id":"22404","normalized":[]},{"id":"22418","type":"CID","arg1_id":"22399","arg2_id":"22406","normalized":[]},{"id":"22419","type":"CID","arg1_id":"22399","arg2_id":"22408","normalized":[]},{"id":"22420","type":"CID","arg1_id":"22399","arg2_id":"22411","normalized":[]},{"id":"22421","type":"CID","arg1_id":"22400","arg2_id":"22404","normalized":[]},{"id":"22422","type":"CID","arg1_id":"22400","arg2_id":"22406","normalized":[]},{"id":"22423","type":"CID","arg1_id":"22400","arg2_id":"22408","normalized":[]},{"id":"22424","type":"CID","arg1_id":"22400","arg2_id":"22411","normalized":[]},{"id":"22425","type":"CID","arg1_id":"22401","arg2_id":"22404","normalized":[]},{"id":"22426","type":"CID","arg1_id":"22401","arg2_id":"22406","normalized":[]},{"id":"22427","type":"CID","arg1_id":"22401","arg2_id":"22408","normalized":[]},{"id":"22428","type":"CID","arg1_id":"22401","arg2_id":"22411","normalized":[]},{"id":"22429","type":"CID","arg1_id":"22405","arg2_id":"22404","normalized":[]},{"id":"22430","type":"CID","arg1_id":"22405","arg2_id":"22406","normalized":[]},{"id":"22431","type":"CID","arg1_id":"22405","arg2_id":"22408","normalized":[]},{"id":"22432","type":"CID","arg1_id":"22405","arg2_id":"22411","normalized":[]}]}
{"id":"22433","document_id":"18703024","passages":[{"id":"22434","type":"title","text":["Prenatal protein deprivation alters dopamine-mediated behaviors and dopaminergic and glutamatergic receptor binding."],"offsets":[[0,116]]},{"id":"22435","type":"abstract","text":["Epidemiological evidence indicates that prenatal nutritional deprivation may increase the risk of schizophrenia. The goal of these studies was to use an animal model to examine the effects of prenatal protein deprivation on behaviors and receptor binding with relevance to schizophrenia. We report that prenatally protein deprived (PD) female rats showed an increased stereotypic response to apomorphine and an increased locomotor response to amphetamine in adulthood. These differences were not observed during puberty. No changes in haloperidol-induced catalepsy or MK-801-induced locomotion were seen following PD. In addition, PD female rats showed increased (3)H-MK-801 binding in the striatum and hippocampus, but not in the cortex. PD female rats also showed increased (3)H-haloperidol binding and decreased dopamine transporter binding in striatum. No statistically significant changes in behavior or receptor binding were found in PD males with the exception of increased (3)H-MK-801 binding in cortex. This animal model may be useful to explore the mechanisms by which prenatal nutritional deficiency enhances risk for schizophrenia in humans and may also have implications for developmental processes leading to differential sensitivity to drugs of abuse."],"offsets":[[117,1383]]}],"entities":[{"id":"22436","type":"Chemical","text":["dopamine"],"offsets":[[36,44]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"22437","type":"Disease","text":["schizophrenia"],"offsets":[[215,228]],"normalized":[{"db_name":"MESH","db_id":"D012559"}]},{"id":"22438","type":"Disease","text":["schizophrenia"],"offsets":[[390,403]],"normalized":[{"db_name":"MESH","db_id":"D012559"}]},{"id":"22439","type":"Chemical","text":["apomorphine"],"offsets":[[509,520]],"normalized":[{"db_name":"MESH","db_id":"D001058"}]},{"id":"22440","type":"Chemical","text":["amphetamine"],"offsets":[[560,571]],"normalized":[{"db_name":"MESH","db_id":"D000661"}]},{"id":"22441","type":"Chemical","text":["haloperidol"],"offsets":[[652,663]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"22442","type":"Disease","text":["catalepsy"],"offsets":[[672,681]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"22443","type":"Chemical","text":["MK-801"],"offsets":[[685,691]],"normalized":[{"db_name":"MESH","db_id":"D016291"}]},{"id":"22444","type":"Chemical","text":["H"],"offsets":[[783,784]],"normalized":[{"db_name":"MESH","db_id":"D006859"}]},{"id":"22445","type":"Chemical","text":["MK-801"],"offsets":[[785,791]],"normalized":[{"db_name":"MESH","db_id":"D016291"}]},{"id":"22446","type":"Chemical","text":["H"],"offsets":[[896,897]],"normalized":[{"db_name":"MESH","db_id":"D006859"}]},{"id":"22447","type":"Chemical","text":["haloperidol"],"offsets":[[898,909]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"22448","type":"Chemical","text":["dopamine"],"offsets":[[932,940]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"22449","type":"Chemical","text":["H"],"offsets":[[1101,1102]],"normalized":[{"db_name":"MESH","db_id":"D006859"}]},{"id":"22450","type":"Chemical","text":["MK-801"],"offsets":[[1103,1109]],"normalized":[{"db_name":"MESH","db_id":"D016291"}]},{"id":"22451","type":"Disease","text":["nutritional deficiency"],"offsets":[[1205,1227]],"normalized":[{"db_name":"MESH","db_id":"D044342"}]},{"id":"22452","type":"Disease","text":["schizophrenia"],"offsets":[[1246,1259]],"normalized":[{"db_name":"MESH","db_id":"D012559"}]}],"events":[],"coreferences":[],"relations":[{"id":"22453","type":"CID","arg1_id":"22441","arg2_id":"22442","normalized":[]},{"id":"22454","type":"CID","arg1_id":"22447","arg2_id":"22442","normalized":[]}]}
{"id":"22455","document_id":"18631865","passages":[{"id":"22456","type":"title","text":["mToR inhibitors-induced proteinuria: mechanisms, significance, and management."],"offsets":[[0,78]]},{"id":"22457","type":"abstract","text":["Massive urinary protein excretion has been observed after conversion from calcineurin inhibitors to mammalian target of rapamycin (mToR) inhibitors, especially sirolimus, in renal transplant recipients with chronic allograft nephropathy. Because proteinuria is a major predictive factor of poor transplantation outcome, many studies focused on this adverse event during the past years. Whether proteinuria was due to sirolimus or only a consequence of calcineurin inhibitors withdrawal remained unsolved until high range proteinuria has been observed during sirolimus therapy in islet transplantation and in patients who received sirolimus de novo. Podocyte injury and focal segmental glomerulosclerosis have been related to mToR inhibition in some patients, but the pathways underlying these lesions remain hypothetic. We discuss herein the possible mechanisms and the significance of mToR blockade-induced proteinuria."],"offsets":[[79,999]]}],"entities":[{"id":"22458","type":"Disease","text":["proteinuria"],"offsets":[[24,35]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]},{"id":"22459","type":"Chemical","text":["rapamycin"],"offsets":[[199,208]],"normalized":[{"db_name":"MESH","db_id":"D020123"}]},{"id":"22460","type":"Chemical","text":["sirolimus"],"offsets":[[239,248]],"normalized":[{"db_name":"MESH","db_id":"D020123"}]},{"id":"22461","type":"Disease","text":["chronic allograft nephropathy"],"offsets":[[286,315]],"normalized":[{"db_name":"MESH","db_id":"D051436"}]},{"id":"22462","type":"Disease","text":["proteinuria"],"offsets":[[325,336]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]},{"id":"22463","type":"Disease","text":["proteinuria"],"offsets":[[473,484]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]},{"id":"22464","type":"Chemical","text":["sirolimus"],"offsets":[[496,505]],"normalized":[{"db_name":"MESH","db_id":"D020123"}]},{"id":"22465","type":"Disease","text":["proteinuria"],"offsets":[[600,611]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]},{"id":"22466","type":"Chemical","text":["sirolimus"],"offsets":[[637,646]],"normalized":[{"db_name":"MESH","db_id":"D020123"}]},{"id":"22467","type":"Chemical","text":["sirolimus"],"offsets":[[709,718]],"normalized":[{"db_name":"MESH","db_id":"D020123"}]},{"id":"22468","type":"Disease","text":["glomerulosclerosis"],"offsets":[[764,782]],"normalized":[{"db_name":"MESH","db_id":"D005921"}]},{"id":"22469","type":"Disease","text":["proteinuria"],"offsets":[[987,998]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]}],"events":[],"coreferences":[],"relations":[{"id":"22470","type":"CID","arg1_id":"22459","arg2_id":"22458","normalized":[]},{"id":"22471","type":"CID","arg1_id":"22459","arg2_id":"22462","normalized":[]},{"id":"22472","type":"CID","arg1_id":"22459","arg2_id":"22463","normalized":[]},{"id":"22473","type":"CID","arg1_id":"22459","arg2_id":"22465","normalized":[]},{"id":"22474","type":"CID","arg1_id":"22459","arg2_id":"22469","normalized":[]},{"id":"22475","type":"CID","arg1_id":"22460","arg2_id":"22458","normalized":[]},{"id":"22476","type":"CID","arg1_id":"22460","arg2_id":"22462","normalized":[]},{"id":"22477","type":"CID","arg1_id":"22460","arg2_id":"22463","normalized":[]},{"id":"22478","type":"CID","arg1_id":"22460","arg2_id":"22465","normalized":[]},{"id":"22479","type":"CID","arg1_id":"22460","arg2_id":"22469","normalized":[]},{"id":"22480","type":"CID","arg1_id":"22464","arg2_id":"22458","normalized":[]},{"id":"22481","type":"CID","arg1_id":"22464","arg2_id":"22462","normalized":[]},{"id":"22482","type":"CID","arg1_id":"22464","arg2_id":"22463","normalized":[]},{"id":"22483","type":"CID","arg1_id":"22464","arg2_id":"22465","normalized":[]},{"id":"22484","type":"CID","arg1_id":"22464","arg2_id":"22469","normalized":[]},{"id":"22485","type":"CID","arg1_id":"22466","arg2_id":"22458","normalized":[]},{"id":"22486","type":"CID","arg1_id":"22466","arg2_id":"22462","normalized":[]},{"id":"22487","type":"CID","arg1_id":"22466","arg2_id":"22463","normalized":[]},{"id":"22488","type":"CID","arg1_id":"22466","arg2_id":"22465","normalized":[]},{"id":"22489","type":"CID","arg1_id":"22466","arg2_id":"22469","normalized":[]},{"id":"22490","type":"CID","arg1_id":"22467","arg2_id":"22458","normalized":[]},{"id":"22491","type":"CID","arg1_id":"22467","arg2_id":"22462","normalized":[]},{"id":"22492","type":"CID","arg1_id":"22467","arg2_id":"22463","normalized":[]},{"id":"22493","type":"CID","arg1_id":"22467","arg2_id":"22465","normalized":[]},{"id":"22494","type":"CID","arg1_id":"22467","arg2_id":"22469","normalized":[]}]}
{"id":"22495","document_id":"18162529","passages":[{"id":"22496","type":"title","text":["Hypothalamic prolactin receptor messenger ribonucleic acid levels, prolactin signaling, and hyperprolactinemic inhibition of pulsatile luteinizing hormone secretion are dependent on estradiol."],"offsets":[[0,192]]},{"id":"22497","type":"abstract","text":["Hyperprolactinemia can reduce fertility and libido. Although central prolactin actions are thought to contribute to this, the mechanisms are poorly understood. We first tested whether chronic hyperprolactinemia inhibited two neuroendocrine parameters necessary for female fertility: pulsatile LH secretion and the estrogen-induced LH surge. Chronic hyperprolactinemia induced by the dopamine antagonist sulpiride caused a 40% reduction LH pulse frequency in ovariectomized rats, but only in the presence of chronic low levels of estradiol. Sulpiride did not affect the magnitude of a steroid-induced LH surge or the percentage of GnRH neurons activated during the surge. Estradiol is known to influence expression of the long form of prolactin receptors (PRL-R) and components of prolactin's signaling pathway. To test the hypothesis that estrogen increases PRL-R expression and sensitivity to prolactin, we next demonstrated that estradiol greatly augments prolactin-induced STAT5 activation. Lastly, we measured PRL-R and suppressor of cytokine signaling (SOCS-1 and -3 and CIS, which reflect the level of prolactin signaling) mRNAs in response to sulpiride and estradiol. Sulpiride induced only SOCS-1 in the medial preoptic area, where GnRH neurons are regulated, but in the arcuate nucleus and choroid plexus, PRL-R, SOCS-3, and CIS mRNA levels were also induced. Estradiol enhanced these effects on SOCS-3 and CIS. Interestingly, estradiol also induced PRL-R, SOCS-3, and CIS mRNA levels independently. These data show that GnRH pulse frequency is inhibited by chronic hyperprolactinemia in a steroid-dependent manner. They also provide evidence for estradiol-dependent and brain region-specific regulation of PRL-R expression and signaling responses by prolactin."],"offsets":[[193,1963]]}],"entities":[{"id":"22498","type":"Chemical","text":["ribonucleic acid"],"offsets":[[42,58]],"normalized":[{"db_name":"MESH","db_id":"D012313"}]},{"id":"22499","type":"Disease","text":["hyperprolactinemic"],"offsets":[[92,110]],"normalized":[{"db_name":"MESH","db_id":"D006966"}]},{"id":"22500","type":"Chemical","text":["estradiol"],"offsets":[[182,191]],"normalized":[{"db_name":"MESH","db_id":"D004958"}]},{"id":"22501","type":"Disease","text":["Hyperprolactinemia"],"offsets":[[193,211]],"normalized":[{"db_name":"MESH","db_id":"D006966"}]},{"id":"22502","type":"Disease","text":["hyperprolactinemia"],"offsets":[[385,403]],"normalized":[{"db_name":"MESH","db_id":"D006966"}]},{"id":"22503","type":"Chemical","text":["estrogen"],"offsets":[[507,515]],"normalized":[{"db_name":"MESH","db_id":"D004967"}]},{"id":"22504","type":"Disease","text":["hyperprolactinemia"],"offsets":[[542,560]],"normalized":[{"db_name":"MESH","db_id":"D006966"}]},{"id":"22505","type":"Chemical","text":["dopamine"],"offsets":[[576,584]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"22506","type":"Chemical","text":["sulpiride"],"offsets":[[596,605]],"normalized":[{"db_name":"MESH","db_id":"D013469"}]},{"id":"22507","type":"Chemical","text":["estradiol"],"offsets":[[722,731]],"normalized":[{"db_name":"MESH","db_id":"D004958"}]},{"id":"22508","type":"Chemical","text":["Sulpiride"],"offsets":[[733,742]],"normalized":[{"db_name":"MESH","db_id":"D013469"}]},{"id":"22509","type":"Chemical","text":["steroid"],"offsets":[[777,784]],"normalized":[{"db_name":"MESH","db_id":"D013256"}]},{"id":"22510","type":"Chemical","text":["Estradiol"],"offsets":[[864,873]],"normalized":[{"db_name":"MESH","db_id":"D004958"}]},{"id":"22511","type":"Chemical","text":["estrogen"],"offsets":[[1032,1040]],"normalized":[{"db_name":"MESH","db_id":"D004967"}]},{"id":"22512","type":"Chemical","text":["estradiol"],"offsets":[[1124,1133]],"normalized":[{"db_name":"MESH","db_id":"D004958"}]},{"id":"22513","type":"Chemical","text":["sulpiride"],"offsets":[[1343,1352]],"normalized":[{"db_name":"MESH","db_id":"D013469"}]},{"id":"22514","type":"Chemical","text":["estradiol"],"offsets":[[1357,1366]],"normalized":[{"db_name":"MESH","db_id":"D004958"}]},{"id":"22515","type":"Chemical","text":["Sulpiride"],"offsets":[[1368,1377]],"normalized":[{"db_name":"MESH","db_id":"D013469"}]},{"id":"22516","type":"Chemical","text":["Estradiol"],"offsets":[[1562,1571]],"normalized":[{"db_name":"MESH","db_id":"D004958"}]},{"id":"22517","type":"Chemical","text":["estradiol"],"offsets":[[1629,1638]],"normalized":[{"db_name":"MESH","db_id":"D004958"}]},{"id":"22518","type":"Disease","text":["hyperprolactinemia"],"offsets":[[1768,1786]],"normalized":[{"db_name":"MESH","db_id":"D006966"}]},{"id":"22519","type":"Chemical","text":["steroid"],"offsets":[[1792,1799]],"normalized":[{"db_name":"MESH","db_id":"D013256"}]},{"id":"22520","type":"Chemical","text":["estradiol"],"offsets":[[1849,1858]],"normalized":[{"db_name":"MESH","db_id":"D004958"}]}],"events":[],"coreferences":[],"relations":[{"id":"22521","type":"CID","arg1_id":"22506","arg2_id":"22499","normalized":[]},{"id":"22522","type":"CID","arg1_id":"22506","arg2_id":"22501","normalized":[]},{"id":"22523","type":"CID","arg1_id":"22506","arg2_id":"22502","normalized":[]},{"id":"22524","type":"CID","arg1_id":"22506","arg2_id":"22504","normalized":[]},{"id":"22525","type":"CID","arg1_id":"22506","arg2_id":"22518","normalized":[]},{"id":"22526","type":"CID","arg1_id":"22508","arg2_id":"22499","normalized":[]},{"id":"22527","type":"CID","arg1_id":"22508","arg2_id":"22501","normalized":[]},{"id":"22528","type":"CID","arg1_id":"22508","arg2_id":"22502","normalized":[]},{"id":"22529","type":"CID","arg1_id":"22508","arg2_id":"22504","normalized":[]},{"id":"22530","type":"CID","arg1_id":"22508","arg2_id":"22518","normalized":[]},{"id":"22531","type":"CID","arg1_id":"22513","arg2_id":"22499","normalized":[]},{"id":"22532","type":"CID","arg1_id":"22513","arg2_id":"22501","normalized":[]},{"id":"22533","type":"CID","arg1_id":"22513","arg2_id":"22502","normalized":[]},{"id":"22534","type":"CID","arg1_id":"22513","arg2_id":"22504","normalized":[]},{"id":"22535","type":"CID","arg1_id":"22513","arg2_id":"22518","normalized":[]},{"id":"22536","type":"CID","arg1_id":"22515","arg2_id":"22499","normalized":[]},{"id":"22537","type":"CID","arg1_id":"22515","arg2_id":"22501","normalized":[]},{"id":"22538","type":"CID","arg1_id":"22515","arg2_id":"22502","normalized":[]},{"id":"22539","type":"CID","arg1_id":"22515","arg2_id":"22504","normalized":[]},{"id":"22540","type":"CID","arg1_id":"22515","arg2_id":"22518","normalized":[]}]}
{"id":"22541","document_id":"17879945","passages":[{"id":"22542","type":"title","text":["Estrogen prevents cholesteryl ester accumulation in macrophages induced by the HIV protease inhibitor ritonavir."],"offsets":[[0,112]]},{"id":"22543","type":"abstract","text":["Individuals with HIV can now live long lives with drug therapy that often includes protease inhibitors such as ritonavir. Many patients, however, develop negative long-term side effects such as premature atherosclerosis. We have previously demonstrated that ritonavir treatment increases atherosclerotic lesion formation in male mice to a greater extent than in female mice. Furthermore, peripheral blood monocytes isolated from ritonavir-treated females had less cholesteryl ester accumulation. In the present study, we have investigated the molecular mechanisms by which female hormones influence cholesterol metabolism in macrophages in response to the HIV protease inhibitor ritonavir. We have utilized the human monocyte cell line, THP-1 as a model to address this question. Briefly, cells were differentiated for 72 h with 100 nM PMA to obtain a macrophage-like phenotype in the presence or absence of 1 nM 17beta-estradiol (E2), 100 nM progesterone or vehicle (0.01% ethanol). Cells were then treated with 30 ng\/ml ritonavir or vehicle in the presence of aggregated LDL for 24 h. Cell extracts were harvested, and lipid or total RNA was isolated. E2 decreased the accumulation of cholesteryl esters in macrophages following ritonavir treatment. Ritonavir increased the expression of the scavenger receptor, CD36 mRNA, responsible for the uptake of LDL. Additionally, ritonavir treatment selectively increased the relative levels of PPARgamma mRNA, a transcription factor responsible for the regulation of CD36 mRNA expression. Treatment with E2, however, failed to prevent these increases at the mRNA level. E2 did, however, significantly suppress CD36 protein levels as measured by fluorescent immunocytochemistry. This data suggests that E2 modifies the expression of CD36 at the level of protein expression in monocyte-derived macrophages resulting in reduced cholesteryl ester accumulation following ritonavir treatment."],"offsets":[[113,2044]]}],"entities":[{"id":"22544","type":"Chemical","text":["cholesteryl ester"],"offsets":[[18,35]],"normalized":[{"db_name":"MESH","db_id":"D002788"}]},{"id":"22545","type":"Chemical","text":["ritonavir"],"offsets":[[102,111]],"normalized":[{"db_name":"MESH","db_id":"D019438"}]},{"id":"22546","type":"Chemical","text":["ritonavir"],"offsets":[[224,233]],"normalized":[{"db_name":"MESH","db_id":"D019438"}]},{"id":"22547","type":"Disease","text":["premature atherosclerosis"],"offsets":[[307,332]],"normalized":[{"db_name":"MESH","db_id":"D050197"}]},{"id":"22548","type":"Chemical","text":["ritonavir"],"offsets":[[371,380]],"normalized":[{"db_name":"MESH","db_id":"D019438"}]},{"id":"22549","type":"Disease","text":["atherosclerotic lesion"],"offsets":[[401,423]],"normalized":[{"db_name":"MESH","db_id":"D050197"}]},{"id":"22550","type":"Chemical","text":["ritonavir"],"offsets":[[542,551]],"normalized":[{"db_name":"MESH","db_id":"D019438"}]},{"id":"22551","type":"Chemical","text":["cholesteryl ester"],"offsets":[[577,594]],"normalized":[{"db_name":"MESH","db_id":"D002788"}]},{"id":"22552","type":"Chemical","text":["cholesterol"],"offsets":[[712,723]],"normalized":[{"db_name":"MESH","db_id":"D002784"}]},{"id":"22553","type":"Chemical","text":["ritonavir"],"offsets":[[792,801]],"normalized":[{"db_name":"MESH","db_id":"D019438"}]},{"id":"22554","type":"Chemical","text":["17beta-estradiol"],"offsets":[[1026,1042]],"normalized":[{"db_name":"MESH","db_id":"D004958"}]},{"id":"22555","type":"Chemical","text":["E2"],"offsets":[[1044,1046]],"normalized":[{"db_name":"MESH","db_id":"D004958"}]},{"id":"22556","type":"Chemical","text":["progesterone"],"offsets":[[1056,1068]],"normalized":[{"db_name":"MESH","db_id":"D011374"}]},{"id":"22557","type":"Chemical","text":["ethanol"],"offsets":[[1087,1094]],"normalized":[{"db_name":"MESH","db_id":"D000431"}]},{"id":"22558","type":"Chemical","text":["ritonavir"],"offsets":[[1135,1144]],"normalized":[{"db_name":"MESH","db_id":"D019438"}]},{"id":"22559","type":"Chemical","text":["E2"],"offsets":[[1267,1269]],"normalized":[{"db_name":"MESH","db_id":"D004958"}]},{"id":"22560","type":"Chemical","text":["cholesteryl esters"],"offsets":[[1300,1318]],"normalized":[{"db_name":"MESH","db_id":"D002788"}]},{"id":"22561","type":"Chemical","text":["ritonavir"],"offsets":[[1344,1353]],"normalized":[{"db_name":"MESH","db_id":"D019438"}]},{"id":"22562","type":"Chemical","text":["Ritonavir"],"offsets":[[1365,1374]],"normalized":[{"db_name":"MESH","db_id":"D019438"}]},{"id":"22563","type":"Chemical","text":["ritonavir"],"offsets":[[1487,1496]],"normalized":[{"db_name":"MESH","db_id":"D019438"}]},{"id":"22564","type":"Chemical","text":["E2"],"offsets":[[1662,1664]],"normalized":[{"db_name":"MESH","db_id":"D004958"}]},{"id":"22565","type":"Chemical","text":["E2"],"offsets":[[1728,1730]],"normalized":[{"db_name":"MESH","db_id":"D004958"}]},{"id":"22566","type":"Chemical","text":["E2"],"offsets":[[1860,1862]],"normalized":[{"db_name":"MESH","db_id":"D004958"}]},{"id":"22567","type":"Chemical","text":["cholesteryl ester"],"offsets":[[1983,2000]],"normalized":[{"db_name":"MESH","db_id":"D002788"}]},{"id":"22568","type":"Chemical","text":["ritonavir"],"offsets":[[2024,2033]],"normalized":[{"db_name":"MESH","db_id":"D019438"}]}],"events":[],"coreferences":[],"relations":[{"id":"22569","type":"CID","arg1_id":"22545","arg2_id":"22547","normalized":[]},{"id":"22570","type":"CID","arg1_id":"22545","arg2_id":"22549","normalized":[]},{"id":"22571","type":"CID","arg1_id":"22546","arg2_id":"22547","normalized":[]},{"id":"22572","type":"CID","arg1_id":"22546","arg2_id":"22549","normalized":[]},{"id":"22573","type":"CID","arg1_id":"22548","arg2_id":"22547","normalized":[]},{"id":"22574","type":"CID","arg1_id":"22548","arg2_id":"22549","normalized":[]},{"id":"22575","type":"CID","arg1_id":"22550","arg2_id":"22547","normalized":[]},{"id":"22576","type":"CID","arg1_id":"22550","arg2_id":"22549","normalized":[]},{"id":"22577","type":"CID","arg1_id":"22553","arg2_id":"22547","normalized":[]},{"id":"22578","type":"CID","arg1_id":"22553","arg2_id":"22549","normalized":[]},{"id":"22579","type":"CID","arg1_id":"22558","arg2_id":"22547","normalized":[]},{"id":"22580","type":"CID","arg1_id":"22558","arg2_id":"22549","normalized":[]},{"id":"22581","type":"CID","arg1_id":"22561","arg2_id":"22547","normalized":[]},{"id":"22582","type":"CID","arg1_id":"22561","arg2_id":"22549","normalized":[]},{"id":"22583","type":"CID","arg1_id":"22562","arg2_id":"22547","normalized":[]},{"id":"22584","type":"CID","arg1_id":"22562","arg2_id":"22549","normalized":[]},{"id":"22585","type":"CID","arg1_id":"22563","arg2_id":"22547","normalized":[]},{"id":"22586","type":"CID","arg1_id":"22563","arg2_id":"22549","normalized":[]},{"id":"22587","type":"CID","arg1_id":"22568","arg2_id":"22547","normalized":[]},{"id":"22588","type":"CID","arg1_id":"22568","arg2_id":"22549","normalized":[]}]}
{"id":"22589","document_id":"17437408","passages":[{"id":"22590","type":"title","text":["Upregulation of brain expression of P-glycoprotein in MRP2-deficient TR(-) rats resembles seizure-induced up-regulation of this drug efflux transporter in normal rats."],"offsets":[[0,167]]},{"id":"22591","type":"abstract","text":["PURPOSE: The multidrug resistance protein 2 (MRP2) is a drug efflux transporter that is expressed predominantly at the apical domain of hepatocytes but seems also to be expressed at the apical membrane of brain capillary endothelial cells that form the blood-brain barrier (BBB). MRP2 is absent in the transport-deficient (TR(-)) Wistar rat mutant, so that this rat strain was very helpful in defining substrates of MRP2 by comparing tissue concentrations or functional activities of compounds in MRP2-deficient rats with those in transport-competent Wistar rats. By using this strategy to study the involvement of MRP2 in brain access of antiepileptic drugs (AEDs), we recently reported that phenytoin is a substrate for MRP2 in the BBB. However, one drawback of such studies in genetically deficient rats is the fact that compensatory changes with upregulation of other transporters can occur. This prompted us to study the brain expression of P-glycoprotein (Pgp), a major drug efflux transporter in many tissues, including the BBB, in TR(-) rats compared with nonmutant (wild-type) Wistar rats. METHODS: The expression of MRP2 and Pgp in brain and liver sections of TR(-) rats and normal Wistar rats was determined with immunohistochemistry, by using a novel, highly selective monoclonal MRP2 antibody and the monoclonal Pgp antibody C219, respectively. RESULTS: Immunofluorescence staining with the MRP2 antibody was found to label a high number of microvessels throughout the brain in normal Wistar rats, whereas such labeling was absent in TR(-) rats. TR(-) rats exhibited a significant up-regulation of Pgp in brain capillary endothelial cells compared with wild-type controls. No such obvious upregulation of Pgp was observed in liver sections. A comparable overexpression of Pgp in the BBB was obtained after pilocarpine-induced seizures in wild-type Wistar rats. Experiments with systemic administration of the Pgp substrate phenobarbital and the selective Pgp inhibitor tariquidar in TR(-) rats substantiated that Pgp is functional and compensates for the lack of MRP2 in the BBB. CONCLUSIONS: The data on TR(-) rats indicate that Pgp plays an important role in the compensation of MRP2 deficiency in the BBB. Because such a compensatory mechanism most likely occurs to reduce injury to the brain from cytotoxic compounds, the present data substantiate the concept that MRP2 performs a protective role in the BBB. Furthermore, our data suggest that TR(-) rats are an interesting tool to study consequences of overexpression of Pgp in the BBB on access of drugs in the brain, without the need of inducing seizures or other Pgp-enhancing events for this purpose."],"offsets":[[168,2840]]}],"entities":[{"id":"22592","type":"Disease","text":["seizure"],"offsets":[[90,97]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"22593","type":"Chemical","text":["phenytoin"],"offsets":[[861,870]],"normalized":[{"db_name":"MESH","db_id":"D010672"}]},{"id":"22594","type":"Chemical","text":["pilocarpine"],"offsets":[[1987,1998]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"22595","type":"Disease","text":["seizures"],"offsets":[[2007,2015]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"22596","type":"Chemical","text":["phenobarbital"],"offsets":[[2104,2117]],"normalized":[{"db_name":"MESH","db_id":"D010634"}]},{"id":"22597","type":"Chemical","text":["tariquidar"],"offsets":[[2150,2160]],"normalized":[{"db_name":"MESH","db_id":"C402343"}]},{"id":"22598","type":"Disease","text":["injury to the brain"],"offsets":[[2457,2476]],"normalized":[{"db_name":"MESH","db_id":"D001927"}]},{"id":"22599","type":"Disease","text":["seizures"],"offsets":[[2784,2792]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]}],"events":[],"coreferences":[],"relations":[{"id":"22600","type":"CID","arg1_id":"22594","arg2_id":"22592","normalized":[]},{"id":"22601","type":"CID","arg1_id":"22594","arg2_id":"22595","normalized":[]},{"id":"22602","type":"CID","arg1_id":"22594","arg2_id":"22599","normalized":[]}]}
{"id":"22603","document_id":"17242861","passages":[{"id":"22604","type":"title","text":["Use of chromosome substitution strains to identify seizure susceptibility loci in mice."],"offsets":[[0,87]]},{"id":"22605","type":"abstract","text":["Seizure susceptibility varies among inbred mouse strains. Chromosome substitution strains (CSS), in which a single chromosome from one inbred strain (donor) has been transferred onto a second strain (host) by repeated backcrossing, may be used to identify quantitative trait loci (QTLs) that contribute to seizure susceptibility. QTLs for susceptibility to pilocarpine-induced seizures, a model of temporal lobe epilepsy, have not been reported, and CSS have not previously been used to localize seizure susceptibility genes. We report QTLs identified using a B6 (host) x A\/J (donor) CSS panel to localize genes involved in susceptibility to pilocarpine-induced seizures. Three hundred fifty-five adult male CSS mice, 58 B6, and 39 A\/J were tested for susceptibility to pilocarpine-induced seizures. Highest stage reached and latency to each stage were recorded for all mice. B6 mice were resistant to seizures and slower to reach stages compared to A\/J mice. The CSS for Chromosomes 10 and 18 progressed to the most severe stages, diverging dramatically from the B6 phenotype. Latencies to stages were also significantly shorter for CSS10 and CSS18 mice. CSS mapping suggests seizure susceptibility loci on mouse Chromosomes 10 and 18. This approach provides a framework for identifying potentially novel homologous candidate genes for human temporal lobe epilepsy."],"offsets":[[88,1454]]}],"entities":[{"id":"22606","type":"Disease","text":["seizure"],"offsets":[[51,58]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"22607","type":"Disease","text":["Seizure"],"offsets":[[88,95]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"22608","type":"Disease","text":["seizure"],"offsets":[[394,401]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"22609","type":"Chemical","text":["pilocarpine"],"offsets":[[445,456]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"22610","type":"Disease","text":["seizures"],"offsets":[[465,473]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"22611","type":"Disease","text":["temporal lobe epilepsy"],"offsets":[[486,508]],"normalized":[{"db_name":"MESH","db_id":"D004833"}]},{"id":"22612","type":"Disease","text":["seizure"],"offsets":[[584,591]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"22613","type":"Chemical","text":["pilocarpine"],"offsets":[[730,741]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"22614","type":"Disease","text":["seizures"],"offsets":[[750,758]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"22615","type":"Chemical","text":["pilocarpine"],"offsets":[[858,869]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"22616","type":"Disease","text":["seizures"],"offsets":[[878,886]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"22617","type":"Disease","text":["seizures"],"offsets":[[990,998]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"22618","type":"Disease","text":["seizure"],"offsets":[[1265,1272]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"22619","type":"Disease","text":["temporal lobe epilepsy"],"offsets":[[1431,1453]],"normalized":[{"db_name":"MESH","db_id":"D004833"}]}],"events":[],"coreferences":[],"relations":[{"id":"22620","type":"CID","arg1_id":"22609","arg2_id":"22611","normalized":[]},{"id":"22621","type":"CID","arg1_id":"22609","arg2_id":"22619","normalized":[]},{"id":"22622","type":"CID","arg1_id":"22613","arg2_id":"22611","normalized":[]},{"id":"22623","type":"CID","arg1_id":"22613","arg2_id":"22619","normalized":[]},{"id":"22624","type":"CID","arg1_id":"22615","arg2_id":"22611","normalized":[]},{"id":"22625","type":"CID","arg1_id":"22615","arg2_id":"22619","normalized":[]}]}
{"id":"22626","document_id":"16337777","passages":[{"id":"22627","type":"title","text":["Investigation of mitochondrial involvement in the experimental model of epilepsy induced by pilocarpine."],"offsets":[[0,104]]},{"id":"22628","type":"abstract","text":["Mitochondrial abnormalities have been associated with several aspects of epileptogenesis, such as energy generation, control of cell death, neurotransmitter synthesis, and free radical (FR) production. Increased production of FRs may cause mtDNA damage leading to decreased activities of oxidative phosphorylation complexes containing mtDNA-encoded subunits. In this study, we investigated whether increased generation of FR during status epilepticus would be sufficient to provoke abnormalities in mtDNA and in the expression and activity of cytochrome c oxidase (CCO), complex IV of the respiratory chain, in the chronic phase of the pilocarpine model of temporal lobe epilepsy. DNA analysis revealed low amounts of a 4.8 kb mtDNA deletion but with no differences in frequency or quantity in the control and experimental groups. We did not find abnormalities in the expression and distribution of an mtDNA-encoded subunit of CCO (CCO-I) or a relative decrease in CCO-I when compared with nuclear-encoded subunits (CCO-IV and SDH-fp). No abnormality in CCO activity was observed through histochemistry. Although evidences of mitochondrial abnormalities were found in previously published studies, our results do not suggest that the FRs, generated during the acute phase, determined important abnormalities in mtDNA, in expression of CCO-I, and in CCO activity."],"offsets":[[105,1467]]}],"entities":[{"id":"22629","type":"Disease","text":["epilepsy"],"offsets":[[72,80]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"22630","type":"Chemical","text":["pilocarpine"],"offsets":[[92,103]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"22631","type":"Disease","text":["Mitochondrial abnormalities"],"offsets":[[105,132]],"normalized":[{"db_name":"MESH","db_id":"D028361"}]},{"id":"22632","type":"Disease","text":["death"],"offsets":[[238,243]],"normalized":[{"db_name":"MESH","db_id":"D003643"}]},{"id":"22633","type":"Disease","text":["status epilepticus"],"offsets":[[537,555]],"normalized":[{"db_name":"MESH","db_id":"D013226"}]},{"id":"22634","type":"Chemical","text":["pilocarpine"],"offsets":[[741,752]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"22635","type":"Disease","text":["temporal lobe epilepsy"],"offsets":[[762,784]],"normalized":[{"db_name":"MESH","db_id":"D004833"}]},{"id":"22636","type":"Disease","text":["mitochondrial abnormalities"],"offsets":[[1231,1258]],"normalized":[{"db_name":"MESH","db_id":"D028361"}]}],"events":[],"coreferences":[],"relations":[{"id":"22637","type":"CID","arg1_id":"22630","arg2_id":"22635","normalized":[]},{"id":"22638","type":"CID","arg1_id":"22634","arg2_id":"22635","normalized":[]}]}
{"id":"22639","document_id":"15859940","passages":[{"id":"22640","type":"title","text":["Causes of acute thrombotic microangiopathy in patients receiving kidney transplantation."],"offsets":[[0,88]]},{"id":"22641","type":"abstract","text":["OBJECTIVES: Thrombotic microangiopathy is a well-known problem in patients following renal transplantation. In postrenal transplantation, thrombotic microangiopathy is often a reflection of hemolytic uremic syndrome. We aimed to determine the causes of thrombotic microangiopathy in a population of renal transplantation recipients and discuss the literature. MATERIALS AND METHODS: We investigated the causes of thrombotic microangiopathy during a 1-year period, from June 2003 to June 2004, at the King Fahad National Guard Hospital in Riyadh, Saudi Arabia, by reviewing the slides of all transplant biopsies (n=25) performed during this interval. Pre- and posttransplant crossmatching was done when possible. RESULTS: Five cases of thrombotic microangiopathy were found. Three of these cases were from the 25 transplantations performed at King Fahad National Guard Hospital, while the other 2 transplantations had been performed abroad and were referred to us for follow-up. Three cases were related to cyclosporine, and 1 case was secondary to both cyclosporine and tacrolimus. The fifth case had features of thrombotic microangiopathy related to an antiphospholipid syndrome in a patient with systemic lupus erythematosus. CONCLUSIONS: In the literature, the most-frequent cause of hemolytic uremic syndrome in patients following renal transplantation is recurrence of the hemolytic uremic syndrome. Other causes include drug-related (cyclosporine, tacrolimus) toxicity, procoagulant status, and antibody-mediated rejection. We found that the most-frequent cause of thrombotic microangiopathy was drug related, secondary mainly to cyclosporine. In the current study, the frequency of thrombotic microangiopathy was similar to the percentage reported in the literature (20%)."],"offsets":[[89,1868]]}],"entities":[{"id":"22642","type":"Disease","text":["thrombotic microangiopathy"],"offsets":[[16,42]],"normalized":[{"db_name":"MESH","db_id":"D057049"}]},{"id":"22643","type":"Disease","text":["Thrombotic microangiopathy"],"offsets":[[101,127]],"normalized":[{"db_name":"MESH","db_id":"D057049"}]},{"id":"22644","type":"Disease","text":["thrombotic microangiopathy"],"offsets":[[227,253]],"normalized":[{"db_name":"MESH","db_id":"D057049"}]},{"id":"22645","type":"Disease","text":["hemolytic uremic syndrome"],"offsets":[[279,304]],"normalized":[{"db_name":"MESH","db_id":"D006463"}]},{"id":"22646","type":"Disease","text":["thrombotic microangiopathy"],"offsets":[[342,368]],"normalized":[{"db_name":"MESH","db_id":"D057049"}]},{"id":"22647","type":"Disease","text":["thrombotic microangiopathy"],"offsets":[[502,528]],"normalized":[{"db_name":"MESH","db_id":"D057049"}]},{"id":"22648","type":"Disease","text":["thrombotic microangiopathy"],"offsets":[[824,850]],"normalized":[{"db_name":"MESH","db_id":"D057049"}]},{"id":"22649","type":"Chemical","text":["cyclosporine"],"offsets":[[1095,1107]],"normalized":[{"db_name":"MESH","db_id":"D016572"}]},{"id":"22650","type":"Chemical","text":["cyclosporine"],"offsets":[[1142,1154]],"normalized":[{"db_name":"MESH","db_id":"D016572"}]},{"id":"22651","type":"Chemical","text":["tacrolimus"],"offsets":[[1159,1169]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"22652","type":"Disease","text":["thrombotic microangiopathy"],"offsets":[[1202,1228]],"normalized":[{"db_name":"MESH","db_id":"D057049"}]},{"id":"22653","type":"Disease","text":["antiphospholipid syndrome"],"offsets":[[1243,1268]],"normalized":[{"db_name":"MESH","db_id":"D016736"}]},{"id":"22654","type":"Disease","text":["systemic lupus erythematosus"],"offsets":[[1287,1315]],"normalized":[{"db_name":"MESH","db_id":"D008180"}]},{"id":"22655","type":"Disease","text":["hemolytic uremic syndrome"],"offsets":[[1376,1401]],"normalized":[{"db_name":"MESH","db_id":"D006463"}]},{"id":"22656","type":"Disease","text":["hemolytic uremic syndrome"],"offsets":[[1467,1492]],"normalized":[{"db_name":"MESH","db_id":"D006463"}]},{"id":"22657","type":"Chemical","text":["cyclosporine"],"offsets":[[1529,1541]],"normalized":[{"db_name":"MESH","db_id":"D016572"}]},{"id":"22658","type":"Chemical","text":["tacrolimus"],"offsets":[[1543,1553]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"22659","type":"Disease","text":["toxicity"],"offsets":[[1555,1563]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"22660","type":"Disease","text":["thrombotic microangiopathy"],"offsets":[[1660,1686]],"normalized":[{"db_name":"MESH","db_id":"D057049"}]},{"id":"22661","type":"Chemical","text":["cyclosporine"],"offsets":[[1725,1737]],"normalized":[{"db_name":"MESH","db_id":"D016572"}]},{"id":"22662","type":"Disease","text":["thrombotic microangiopathy"],"offsets":[[1778,1804]],"normalized":[{"db_name":"MESH","db_id":"D057049"}]}],"events":[],"coreferences":[],"relations":[{"id":"22663","type":"CID","arg1_id":"22649","arg2_id":"22642","normalized":[]},{"id":"22664","type":"CID","arg1_id":"22649","arg2_id":"22643","normalized":[]},{"id":"22665","type":"CID","arg1_id":"22649","arg2_id":"22644","normalized":[]},{"id":"22666","type":"CID","arg1_id":"22649","arg2_id":"22646","normalized":[]},{"id":"22667","type":"CID","arg1_id":"22649","arg2_id":"22647","normalized":[]},{"id":"22668","type":"CID","arg1_id":"22649","arg2_id":"22648","normalized":[]},{"id":"22669","type":"CID","arg1_id":"22649","arg2_id":"22652","normalized":[]},{"id":"22670","type":"CID","arg1_id":"22649","arg2_id":"22660","normalized":[]},{"id":"22671","type":"CID","arg1_id":"22649","arg2_id":"22662","normalized":[]},{"id":"22672","type":"CID","arg1_id":"22650","arg2_id":"22642","normalized":[]},{"id":"22673","type":"CID","arg1_id":"22650","arg2_id":"22643","normalized":[]},{"id":"22674","type":"CID","arg1_id":"22650","arg2_id":"22644","normalized":[]},{"id":"22675","type":"CID","arg1_id":"22650","arg2_id":"22646","normalized":[]},{"id":"22676","type":"CID","arg1_id":"22650","arg2_id":"22647","normalized":[]},{"id":"22677","type":"CID","arg1_id":"22650","arg2_id":"22648","normalized":[]},{"id":"22678","type":"CID","arg1_id":"22650","arg2_id":"22652","normalized":[]},{"id":"22679","type":"CID","arg1_id":"22650","arg2_id":"22660","normalized":[]},{"id":"22680","type":"CID","arg1_id":"22650","arg2_id":"22662","normalized":[]},{"id":"22681","type":"CID","arg1_id":"22657","arg2_id":"22642","normalized":[]},{"id":"22682","type":"CID","arg1_id":"22657","arg2_id":"22643","normalized":[]},{"id":"22683","type":"CID","arg1_id":"22657","arg2_id":"22644","normalized":[]},{"id":"22684","type":"CID","arg1_id":"22657","arg2_id":"22646","normalized":[]},{"id":"22685","type":"CID","arg1_id":"22657","arg2_id":"22647","normalized":[]},{"id":"22686","type":"CID","arg1_id":"22657","arg2_id":"22648","normalized":[]},{"id":"22687","type":"CID","arg1_id":"22657","arg2_id":"22652","normalized":[]},{"id":"22688","type":"CID","arg1_id":"22657","arg2_id":"22660","normalized":[]},{"id":"22689","type":"CID","arg1_id":"22657","arg2_id":"22662","normalized":[]},{"id":"22690","type":"CID","arg1_id":"22661","arg2_id":"22642","normalized":[]},{"id":"22691","type":"CID","arg1_id":"22661","arg2_id":"22643","normalized":[]},{"id":"22692","type":"CID","arg1_id":"22661","arg2_id":"22644","normalized":[]},{"id":"22693","type":"CID","arg1_id":"22661","arg2_id":"22646","normalized":[]},{"id":"22694","type":"CID","arg1_id":"22661","arg2_id":"22647","normalized":[]},{"id":"22695","type":"CID","arg1_id":"22661","arg2_id":"22648","normalized":[]},{"id":"22696","type":"CID","arg1_id":"22661","arg2_id":"22652","normalized":[]},{"id":"22697","type":"CID","arg1_id":"22661","arg2_id":"22660","normalized":[]},{"id":"22698","type":"CID","arg1_id":"22661","arg2_id":"22662","normalized":[]}]}
{"id":"22699","document_id":"15188772","passages":[{"id":"22700","type":"title","text":["Severe reversible left ventricular systolic and diastolic dysfunction due to accidental iatrogenic epinephrine overdose."],"offsets":[[0,120]]},{"id":"22701","type":"abstract","text":["Catecholamine-induced cardiomyopathy due to chronic excess of endogenous catecholamines has been recognized for decades as a clinical phenomenon. In contrast, reports of myocardial dysfunction due to acute iatrogenic overdose are rare. A 35-year-old woman whose cervix uteri was inadvertently injected with 8 mg of epinephrine developed myocardial stunning that was characterized by severe hemodynamic compromise, profound, albeit transient, left ventricular systolic and diastolic dysfunction, and only modestly elevated biochemical markers of myocardial necrosis. Our case illustrates the serious consequences of medical errors that can be avoided through improved medication labeling and staff supervision."],"offsets":[[121,830]]}],"entities":[{"id":"22702","type":"Disease","text":["left ventricular systolic and diastolic dysfunction"],"offsets":[[18,69]],"normalized":[{"db_name":"MESH","db_id":"D018487"}]},{"id":"22703","type":"Chemical","text":["epinephrine"],"offsets":[[99,110]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"22704","type":"Disease","text":["overdose"],"offsets":[[111,119]],"normalized":[{"db_name":"MESH","db_id":"D062787"}]},{"id":"22705","type":"Chemical","text":["Catecholamine"],"offsets":[[121,134]],"normalized":[{"db_name":"MESH","db_id":"D002395"}]},{"id":"22706","type":"Disease","text":["cardiomyopathy"],"offsets":[[143,157]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"22707","type":"Chemical","text":["catecholamines"],"offsets":[[194,208]],"normalized":[{"db_name":"MESH","db_id":"D002395"}]},{"id":"22708","type":"Disease","text":["myocardial dysfunction"],"offsets":[[291,313]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"22709","type":"Disease","text":["overdose"],"offsets":[[338,346]],"normalized":[{"db_name":"MESH","db_id":"D062787"}]},{"id":"22710","type":"Chemical","text":["epinephrine"],"offsets":[[436,447]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"22711","type":"Disease","text":["myocardial stunning"],"offsets":[[458,477]],"normalized":[{"db_name":"MESH","db_id":"D017682"}]},{"id":"22712","type":"Disease","text":["left ventricular systolic and diastolic dysfunction"],"offsets":[[563,614]],"normalized":[{"db_name":"MESH","db_id":"D018487"}]},{"id":"22713","type":"Disease","text":["myocardial necrosis"],"offsets":[[666,685]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]}],"events":[],"coreferences":[],"relations":[{"id":"22714","type":"CID","arg1_id":"22703","arg2_id":"22711","normalized":[]},{"id":"22715","type":"CID","arg1_id":"22710","arg2_id":"22711","normalized":[]}]}
{"id":"22716","document_id":"15130900","passages":[{"id":"22717","type":"title","text":["Urinary bladder cancer in Wegener's granulomatosis: risks and relation to cyclophosphamide."],"offsets":[[0,91]]},{"id":"22718","type":"abstract","text":["OBJECTIVE: To assess and characterise the risk of bladder cancer, and its relation to cyclophosphamide, in patients with Wegener's granulomatosis. METHODS: In the population based, nationwide Swedish Inpatient Register a cohort of 1065 patients with Wegener's granulomatosis, 1969-95, was identified. Through linkage with the Swedish Cancer Register, all subjects in this cohort diagnosed with bladder cancer were identified. Nested within the cohort, a matched case-control study was performed to estimate the association between cyclophosphamide and bladder cancer using odds ratios (ORs) as relative risk. In the cohort the cumulative risk of bladder cancer after Wegener's granulomatosis, and the relative prevalence of a history of bladder cancer at the time of diagnosis of Wegener's granulomatosis, were also estimated. RESULTS: The median cumulative doses of cyclophosphamide among cases (n = 11) and controls (n = 25) were 113 g and 25 g, respectively. The risk of bladder cancer doubled for every 10 g increment in cyclophosphamide (OR = 2.0, 95% confidence interval (CI) 0.8 to 4.9). Treatment duration longer than 1 year was associated with an eightfold increased risk (OR = 7.7, 95% CI 0.9 to 69). The absolute risk for bladder cancer in the cohort reached 10% 16 years after diagnosis of Wegener's granulomatosis, and a history of bladder cancer was (non-significantly) twice as common as expected at the time of diagnosis of Wegener's granulomatosis. CONCLUSION: The results indicate a dose-response relationship between cyclophosphamide and the risk of bladder cancer, high cumulative risks in the entire cohort, and also the possibility of risk factors operating even before Wegener's granulomatosis."],"offsets":[[92,1809]]}],"entities":[{"id":"22719","type":"Disease","text":["Urinary bladder cancer"],"offsets":[[0,22]],"normalized":[{"db_name":"MESH","db_id":"D001749"}]},{"id":"22720","type":"Disease","text":["Wegener's granulomatosis"],"offsets":[[26,50]],"normalized":[{"db_name":"MESH","db_id":"D014890"}]},{"id":"22721","type":"Chemical","text":["cyclophosphamide"],"offsets":[[74,90]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"22722","type":"Disease","text":["bladder cancer"],"offsets":[[142,156]],"normalized":[{"db_name":"MESH","db_id":"D001749"}]},{"id":"22723","type":"Chemical","text":["cyclophosphamide"],"offsets":[[178,194]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"22724","type":"Disease","text":["Wegener's granulomatosis"],"offsets":[[213,237]],"normalized":[{"db_name":"MESH","db_id":"D014890"}]},{"id":"22725","type":"Disease","text":["Wegener's granulomatosis"],"offsets":[[342,366]],"normalized":[{"db_name":"MESH","db_id":"D014890"}]},{"id":"22726","type":"Disease","text":["Cancer"],"offsets":[[426,432]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"22727","type":"Disease","text":["bladder cancer"],"offsets":[[486,500]],"normalized":[{"db_name":"MESH","db_id":"D001749"}]},{"id":"22728","type":"Chemical","text":["cyclophosphamide"],"offsets":[[623,639]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"22729","type":"Disease","text":["bladder cancer"],"offsets":[[644,658]],"normalized":[{"db_name":"MESH","db_id":"D001749"}]},{"id":"22730","type":"Disease","text":["bladder cancer"],"offsets":[[738,752]],"normalized":[{"db_name":"MESH","db_id":"D001749"}]},{"id":"22731","type":"Disease","text":["Wegener's granulomatosis"],"offsets":[[759,783]],"normalized":[{"db_name":"MESH","db_id":"D014890"}]},{"id":"22732","type":"Disease","text":["bladder cancer"],"offsets":[[829,843]],"normalized":[{"db_name":"MESH","db_id":"D001749"}]},{"id":"22733","type":"Disease","text":["Wegener's granulomatosis"],"offsets":[[872,896]],"normalized":[{"db_name":"MESH","db_id":"D014890"}]},{"id":"22734","type":"Chemical","text":["cyclophosphamide"],"offsets":[[959,975]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"22735","type":"Disease","text":["bladder cancer"],"offsets":[[1066,1080]],"normalized":[{"db_name":"MESH","db_id":"D001749"}]},{"id":"22736","type":"Chemical","text":["cyclophosphamide"],"offsets":[[1117,1133]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"22737","type":"Disease","text":["bladder cancer"],"offsets":[[1325,1339]],"normalized":[{"db_name":"MESH","db_id":"D001749"}]},{"id":"22738","type":"Disease","text":["Wegener's granulomatosis"],"offsets":[[1394,1418]],"normalized":[{"db_name":"MESH","db_id":"D014890"}]},{"id":"22739","type":"Disease","text":["bladder cancer"],"offsets":[[1437,1451]],"normalized":[{"db_name":"MESH","db_id":"D001749"}]},{"id":"22740","type":"Disease","text":["Wegener's granulomatosis"],"offsets":[[1532,1556]],"normalized":[{"db_name":"MESH","db_id":"D014890"}]},{"id":"22741","type":"Chemical","text":["cyclophosphamide"],"offsets":[[1628,1644]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"22742","type":"Disease","text":["bladder cancer"],"offsets":[[1661,1675]],"normalized":[{"db_name":"MESH","db_id":"D001749"}]},{"id":"22743","type":"Disease","text":["Wegener's granulomatosis"],"offsets":[[1784,1808]],"normalized":[{"db_name":"MESH","db_id":"D014890"}]}],"events":[],"coreferences":[],"relations":[{"id":"22744","type":"CID","arg1_id":"22721","arg2_id":"22719","normalized":[]},{"id":"22745","type":"CID","arg1_id":"22721","arg2_id":"22722","normalized":[]},{"id":"22746","type":"CID","arg1_id":"22721","arg2_id":"22727","normalized":[]},{"id":"22747","type":"CID","arg1_id":"22721","arg2_id":"22729","normalized":[]},{"id":"22748","type":"CID","arg1_id":"22721","arg2_id":"22730","normalized":[]},{"id":"22749","type":"CID","arg1_id":"22721","arg2_id":"22732","normalized":[]},{"id":"22750","type":"CID","arg1_id":"22721","arg2_id":"22735","normalized":[]},{"id":"22751","type":"CID","arg1_id":"22721","arg2_id":"22737","normalized":[]},{"id":"22752","type":"CID","arg1_id":"22721","arg2_id":"22739","normalized":[]},{"id":"22753","type":"CID","arg1_id":"22721","arg2_id":"22742","normalized":[]},{"id":"22754","type":"CID","arg1_id":"22723","arg2_id":"22719","normalized":[]},{"id":"22755","type":"CID","arg1_id":"22723","arg2_id":"22722","normalized":[]},{"id":"22756","type":"CID","arg1_id":"22723","arg2_id":"22727","normalized":[]},{"id":"22757","type":"CID","arg1_id":"22723","arg2_id":"22729","normalized":[]},{"id":"22758","type":"CID","arg1_id":"22723","arg2_id":"22730","normalized":[]},{"id":"22759","type":"CID","arg1_id":"22723","arg2_id":"22732","normalized":[]},{"id":"22760","type":"CID","arg1_id":"22723","arg2_id":"22735","normalized":[]},{"id":"22761","type":"CID","arg1_id":"22723","arg2_id":"22737","normalized":[]},{"id":"22762","type":"CID","arg1_id":"22723","arg2_id":"22739","normalized":[]},{"id":"22763","type":"CID","arg1_id":"22723","arg2_id":"22742","normalized":[]},{"id":"22764","type":"CID","arg1_id":"22728","arg2_id":"22719","normalized":[]},{"id":"22765","type":"CID","arg1_id":"22728","arg2_id":"22722","normalized":[]},{"id":"22766","type":"CID","arg1_id":"22728","arg2_id":"22727","normalized":[]},{"id":"22767","type":"CID","arg1_id":"22728","arg2_id":"22729","normalized":[]},{"id":"22768","type":"CID","arg1_id":"22728","arg2_id":"22730","normalized":[]},{"id":"22769","type":"CID","arg1_id":"22728","arg2_id":"22732","normalized":[]},{"id":"22770","type":"CID","arg1_id":"22728","arg2_id":"22735","normalized":[]},{"id":"22771","type":"CID","arg1_id":"22728","arg2_id":"22737","normalized":[]},{"id":"22772","type":"CID","arg1_id":"22728","arg2_id":"22739","normalized":[]},{"id":"22773","type":"CID","arg1_id":"22728","arg2_id":"22742","normalized":[]},{"id":"22774","type":"CID","arg1_id":"22734","arg2_id":"22719","normalized":[]},{"id":"22775","type":"CID","arg1_id":"22734","arg2_id":"22722","normalized":[]},{"id":"22776","type":"CID","arg1_id":"22734","arg2_id":"22727","normalized":[]},{"id":"22777","type":"CID","arg1_id":"22734","arg2_id":"22729","normalized":[]},{"id":"22778","type":"CID","arg1_id":"22734","arg2_id":"22730","normalized":[]},{"id":"22779","type":"CID","arg1_id":"22734","arg2_id":"22732","normalized":[]},{"id":"22780","type":"CID","arg1_id":"22734","arg2_id":"22735","normalized":[]},{"id":"22781","type":"CID","arg1_id":"22734","arg2_id":"22737","normalized":[]},{"id":"22782","type":"CID","arg1_id":"22734","arg2_id":"22739","normalized":[]},{"id":"22783","type":"CID","arg1_id":"22734","arg2_id":"22742","normalized":[]},{"id":"22784","type":"CID","arg1_id":"22736","arg2_id":"22719","normalized":[]},{"id":"22785","type":"CID","arg1_id":"22736","arg2_id":"22722","normalized":[]},{"id":"22786","type":"CID","arg1_id":"22736","arg2_id":"22727","normalized":[]},{"id":"22787","type":"CID","arg1_id":"22736","arg2_id":"22729","normalized":[]},{"id":"22788","type":"CID","arg1_id":"22736","arg2_id":"22730","normalized":[]},{"id":"22789","type":"CID","arg1_id":"22736","arg2_id":"22732","normalized":[]},{"id":"22790","type":"CID","arg1_id":"22736","arg2_id":"22735","normalized":[]},{"id":"22791","type":"CID","arg1_id":"22736","arg2_id":"22737","normalized":[]},{"id":"22792","type":"CID","arg1_id":"22736","arg2_id":"22739","normalized":[]},{"id":"22793","type":"CID","arg1_id":"22736","arg2_id":"22742","normalized":[]},{"id":"22794","type":"CID","arg1_id":"22741","arg2_id":"22719","normalized":[]},{"id":"22795","type":"CID","arg1_id":"22741","arg2_id":"22722","normalized":[]},{"id":"22796","type":"CID","arg1_id":"22741","arg2_id":"22727","normalized":[]},{"id":"22797","type":"CID","arg1_id":"22741","arg2_id":"22729","normalized":[]},{"id":"22798","type":"CID","arg1_id":"22741","arg2_id":"22730","normalized":[]},{"id":"22799","type":"CID","arg1_id":"22741","arg2_id":"22732","normalized":[]},{"id":"22800","type":"CID","arg1_id":"22741","arg2_id":"22735","normalized":[]},{"id":"22801","type":"CID","arg1_id":"22741","arg2_id":"22737","normalized":[]},{"id":"22802","type":"CID","arg1_id":"22741","arg2_id":"22739","normalized":[]},{"id":"22803","type":"CID","arg1_id":"22741","arg2_id":"22742","normalized":[]}]}
{"id":"22804","document_id":"12707296","passages":[{"id":"22805","type":"title","text":["L-arginine transport in humans with cortisol-induced hypertension."],"offsets":[[0,66]]},{"id":"22806","type":"abstract","text":["A deficient L-arginine-nitric oxide system is implicated in cortisol-induced hypertension. We investigate whether abnormalities in L-arginine uptake contribute to this deficiency. Eight healthy men were recruited. Hydrocortisone acetate (50 mg) was given orally every 6 hours for 24 hours after a 5-day fixed-salt diet (150 mmol\/d). Crossover studies were performed 2 weeks apart. Thirty milliliters of blood was obtained for isolation of peripheral blood mononuclear cells after each treatment period. L-arginine uptake was assessed in mononuclear cells incubated with L-arginine (1 to 300 micromol\/L), incorporating 100 nmol\/L [3H]-l-arginine for a period of 5 minutes at 37 degrees C. Forearm [3H]-L-arginine extraction was calculated after infusion of [3H]-L-arginine into the brachial artery at a rate of 100 nCi\/min for 80 minutes. Deep forearm venous samples were collected for determination of L-arginine extraction. Plasma cortisol concentrations were significantly raised during the active phase (323+\/-43 to 1082+\/-245 mmol\/L, P<0.05). Systolic blood pressure was elevated by an average of 7 mm Hg. Neither L-arginine transport into mononuclear cells (placebo vs active, 26.3+\/-3.6 vs 29.0+\/-2.1 pmol\/10 000 cells per 5 minutes, respectively, at an l-arginine concentration of 300 micromol\/L) nor L-arginine extraction in the forearm (at 80 minutes, placebo vs active, 1 868 904+\/-434 962 vs 2 013 910+\/-770 619 disintegrations per minute) was affected by cortisol treatment; ie, that L-arginine uptake is not affected by short-term cortisol treatment. We conclude that cortisol-induced increases in blood pressure are not associated with abnormalities in the l-arginine transport system."],"offsets":[[67,1766]]}],"entities":[{"id":"22807","type":"Chemical","text":["L-arginine"],"offsets":[[0,10]],"normalized":[{"db_name":"MESH","db_id":"D001120"}]},{"id":"22808","type":"Chemical","text":["cortisol"],"offsets":[[36,44]],"normalized":[{"db_name":"MESH","db_id":"D006854"}]},{"id":"22809","type":"Disease","text":["hypertension"],"offsets":[[53,65]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"22810","type":"Chemical","text":["L-arginine"],"offsets":[[79,89]],"normalized":[{"db_name":"MESH","db_id":"D001120"}]},{"id":"22811","type":"Chemical","text":["nitric oxide"],"offsets":[[90,102]],"normalized":[{"db_name":"MESH","db_id":"D009569"}]},{"id":"22812","type":"Chemical","text":["cortisol"],"offsets":[[127,135]],"normalized":[{"db_name":"MESH","db_id":"D006854"}]},{"id":"22813","type":"Disease","text":["hypertension"],"offsets":[[144,156]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"22814","type":"Chemical","text":["L-arginine"],"offsets":[[198,208]],"normalized":[{"db_name":"MESH","db_id":"D001120"}]},{"id":"22815","type":"Chemical","text":["Hydrocortisone acetate"],"offsets":[[281,303]],"normalized":[{"db_name":"MESH","db_id":"C021650"}]},{"id":"22816","type":"Chemical","text":["L-arginine"],"offsets":[[570,580]],"normalized":[{"db_name":"MESH","db_id":"D001120"}]},{"id":"22817","type":"Chemical","text":["L-arginine"],"offsets":[[637,647]],"normalized":[{"db_name":"MESH","db_id":"D001120"}]},{"id":"22818","type":"Chemical","text":["[3H]-l-arginine"],"offsets":[[696,711]],"normalized":[{"db_name":"MESH","db_id":"D001120"}]},{"id":"22819","type":"Chemical","text":["[3H]-L-arginine"],"offsets":[[763,778]],"normalized":[{"db_name":"MESH","db_id":"D001120"}]},{"id":"22820","type":"Chemical","text":["[3H]-L-arginine"],"offsets":[[823,838]],"normalized":[{"db_name":"MESH","db_id":"D001120"}]},{"id":"22821","type":"Chemical","text":["L-arginine"],"offsets":[[969,979]],"normalized":[{"db_name":"MESH","db_id":"D001120"}]},{"id":"22822","type":"Chemical","text":["cortisol"],"offsets":[[999,1007]],"normalized":[{"db_name":"MESH","db_id":"D006854"}]},{"id":"22823","type":"Chemical","text":["L-arginine"],"offsets":[[1185,1195]],"normalized":[{"db_name":"MESH","db_id":"D001120"}]},{"id":"22824","type":"Chemical","text":["l-arginine"],"offsets":[[1327,1337]],"normalized":[{"db_name":"MESH","db_id":"D001120"}]},{"id":"22825","type":"Chemical","text":["L-arginine"],"offsets":[[1375,1385]],"normalized":[{"db_name":"MESH","db_id":"D001120"}]},{"id":"22826","type":"Chemical","text":["cortisol"],"offsets":[[1534,1542]],"normalized":[{"db_name":"MESH","db_id":"D006854"}]},{"id":"22827","type":"Chemical","text":["L-arginine"],"offsets":[[1563,1573]],"normalized":[{"db_name":"MESH","db_id":"D001120"}]},{"id":"22828","type":"Chemical","text":["cortisol"],"offsets":[[1611,1619]],"normalized":[{"db_name":"MESH","db_id":"D006854"}]},{"id":"22829","type":"Chemical","text":["cortisol"],"offsets":[[1648,1656]],"normalized":[{"db_name":"MESH","db_id":"D006854"}]},{"id":"22830","type":"Disease","text":["increases in blood pressure"],"offsets":[[1665,1692]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"22831","type":"Chemical","text":["l-arginine"],"offsets":[[1738,1748]],"normalized":[{"db_name":"MESH","db_id":"D001120"}]}],"events":[],"coreferences":[],"relations":[{"id":"22832","type":"CID","arg1_id":"22815","arg2_id":"22809","normalized":[]},{"id":"22833","type":"CID","arg1_id":"22815","arg2_id":"22813","normalized":[]},{"id":"22834","type":"CID","arg1_id":"22815","arg2_id":"22830","normalized":[]}]}
{"id":"22835","document_id":"12695819","passages":[{"id":"22836","type":"title","text":["MR imaging with quantitative diffusion mapping of tacrolimus-induced neurotoxicity in organ transplant patients."],"offsets":[[0,112]]},{"id":"22837","type":"abstract","text":["Our objective was to investigate brain MR imaging findings and the utility of diffusion-weighted (DW) imaging in organ transplant patients who developed neurologic symptoms during tacrolimus therapy. Brain MR studies, including DW imaging, were prospectively performed in 14 organ transplant patients receiving tacrolimus who developed neurologic complications. In each patient who had abnormalities on the initial MR study, a follow-up MR study was performed 1 month later. Apparent diffusion coefficient (ADC) values on the initial MR study were correlated with reversibility of the lesions. Of the 14 patients, 5 (35.7%) had white matter abnormalities, 1 (7.1%) had putaminal hemorrhage, and 8 (57.1%) had normal findings on initial MR images. Among the 5 patients with white matter abnormalities, 4 patients (80.0%) showed higher than normal ADC values on initial MR images, and all showed complete resolution on follow-up images. The remaining 1 patient (20.0%) showed lower than normal ADC value and showed incomplete resolution with cortical laminar necrosis. Diffusion-weighted imaging may be useful in predicting the outcomes of the lesions of tacrolimus-induced neurotoxicity."],"offsets":[[113,1299]]}],"entities":[{"id":"22838","type":"Chemical","text":["tacrolimus"],"offsets":[[50,60]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"22839","type":"Disease","text":["neurotoxicity"],"offsets":[[69,82]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"22840","type":"Chemical","text":["tacrolimus"],"offsets":[[293,303]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"22841","type":"Chemical","text":["tacrolimus"],"offsets":[[424,434]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"22842","type":"Disease","text":["neurologic complications"],"offsets":[[449,473]],"normalized":[{"db_name":"MESH","db_id":"D009422"}]},{"id":"22843","type":"Disease","text":["white matter abnormalities"],"offsets":[[741,767]],"normalized":[{"db_name":"MESH","db_id":"D056784"}]},{"id":"22844","type":"Disease","text":["putaminal hemorrhage"],"offsets":[[782,802]],"normalized":[{"db_name":"MESH","db_id":"D020146"}]},{"id":"22845","type":"Disease","text":["white matter abnormalities"],"offsets":[[886,912]],"normalized":[{"db_name":"MESH","db_id":"D056784"}]},{"id":"22846","type":"Disease","text":["cortical laminar necrosis"],"offsets":[[1153,1178]],"normalized":[{"db_name":"MESH","db_id":"D001927"}]},{"id":"22847","type":"Chemical","text":["tacrolimus"],"offsets":[[1266,1276]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"22848","type":"Disease","text":["neurotoxicity"],"offsets":[[1285,1298]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]}],"events":[],"coreferences":[],"relations":[{"id":"22849","type":"CID","arg1_id":"22838","arg2_id":"22843","normalized":[]},{"id":"22850","type":"CID","arg1_id":"22838","arg2_id":"22845","normalized":[]},{"id":"22851","type":"CID","arg1_id":"22840","arg2_id":"22843","normalized":[]},{"id":"22852","type":"CID","arg1_id":"22840","arg2_id":"22845","normalized":[]},{"id":"22853","type":"CID","arg1_id":"22841","arg2_id":"22843","normalized":[]},{"id":"22854","type":"CID","arg1_id":"22841","arg2_id":"22845","normalized":[]},{"id":"22855","type":"CID","arg1_id":"22847","arg2_id":"22843","normalized":[]},{"id":"22856","type":"CID","arg1_id":"22847","arg2_id":"22845","normalized":[]}]}
{"id":"22857","document_id":"12596116","passages":[{"id":"22858","type":"title","text":["Octreotide-induced hypoxemia and pulmonary hypertension in premature neonates."],"offsets":[[0,78]]},{"id":"22859","type":"abstract","text":["The authors report 2 cases of premature neonates who had enterocutaneous fistula complicating necrotizing enterocolitis. Pulmonary hypertension developed after administration of a somatostatin analogue, octreotide, to enhance resolution of the fistula. The authors discuss the mechanism of the occurrence of this complication and recommend caution of its use in high-risk premature neonates."],"offsets":[[79,470]]}],"entities":[{"id":"22860","type":"Chemical","text":["Octreotide"],"offsets":[[0,10]],"normalized":[{"db_name":"MESH","db_id":"D015282"}]},{"id":"22861","type":"Disease","text":["hypoxemia"],"offsets":[[19,28]],"normalized":[{"db_name":"MESH","db_id":"D000860"}]},{"id":"22862","type":"Disease","text":["pulmonary hypertension"],"offsets":[[33,55]],"normalized":[{"db_name":"MESH","db_id":"D006976"}]},{"id":"22863","type":"Disease","text":["fistula"],"offsets":[[152,159]],"normalized":[{"db_name":"MESH","db_id":"D005402"}]},{"id":"22864","type":"Disease","text":["necrotizing enterocolitis"],"offsets":[[173,198]],"normalized":[{"db_name":"MESH","db_id":"D020345"}]},{"id":"22865","type":"Disease","text":["Pulmonary hypertension"],"offsets":[[200,222]],"normalized":[{"db_name":"MESH","db_id":"D006976"}]},{"id":"22866","type":"Chemical","text":["octreotide"],"offsets":[[282,292]],"normalized":[{"db_name":"MESH","db_id":"D015282"}]},{"id":"22867","type":"Disease","text":["fistula"],"offsets":[[323,330]],"normalized":[{"db_name":"MESH","db_id":"D005402"}]}],"events":[],"coreferences":[],"relations":[{"id":"22868","type":"CID","arg1_id":"22860","arg2_id":"22862","normalized":[]},{"id":"22869","type":"CID","arg1_id":"22860","arg2_id":"22865","normalized":[]},{"id":"22870","type":"CID","arg1_id":"22866","arg2_id":"22862","normalized":[]},{"id":"22871","type":"CID","arg1_id":"22866","arg2_id":"22865","normalized":[]}]}
{"id":"22872","document_id":"11875660","passages":[{"id":"22873","type":"title","text":["Sequential observations of exencephaly and subsequent morphological changes by mouse exo utero development system: analysis of the mechanism of transformation from exencephaly to anencephaly."],"offsets":[[0,191]]},{"id":"22874","type":"abstract","text":["Anencephaly has been suggested to develop from exencephaly; however, there is little direct experimental evidence to support this, and the mechanism of transformation remains unclear. We examined this theory using the exo utero development system that allows direct and sequential observations of mid- to late-gestation mouse embryos. We observed the exencephaly induced by 5-azacytidine at embryonic day 13.5 (E13.5), let the embryos develop exo utero until E18.5, and re-observed the same embryos at E18.5. We confirmed several cases of transformation from exencephaly to anencephaly. However, in many cases, the exencephalic brain tissue was preserved with more or less reduction during this period. To analyze the transformation patterns, we classified the exencephaly by size and shape of the exencephalic tissue into several types at E13.5 and E18.5. It was found that the transformation of exencephalic tissue was not simply size-dependent, and all cases of anencephaly at E18.5 resulted from embryos with a large amount of exencephalic tissue at E13.5. Microscopic observation showed the configuration of exencephaly at E13.5, frequent hemorrhaging and detachment of the neural plate from surface ectoderm in the exencephalic head at E15.5, and multiple modes of reduction in the exencephalic tissue at E18.5. From observations of the vasculature, altered distribution patterns of vessels were identified in the exencephalic head. These findings suggest that overgrowth of the exencephalic neural tissue causes the altered distribution patterns of vessels, subsequent peripheral circulatory failure and\/or hemorrhaging in various parts of the exencephalic head, leading to the multiple modes of tissue reduction during transformation from exencephaly to anencephaly."],"offsets":[[192,1966]]}],"entities":[{"id":"22875","type":"Disease","text":["exencephaly"],"offsets":[[27,38]],"normalized":[{"db_name":"MESH","db_id":"D009436"}]},{"id":"22876","type":"Disease","text":["exencephaly"],"offsets":[[164,175]],"normalized":[{"db_name":"MESH","db_id":"D009436"}]},{"id":"22877","type":"Disease","text":["anencephaly"],"offsets":[[179,190]],"normalized":[{"db_name":"MESH","db_id":"D000757"}]},{"id":"22878","type":"Disease","text":["Anencephaly"],"offsets":[[192,203]],"normalized":[{"db_name":"MESH","db_id":"D000757"}]},{"id":"22879","type":"Disease","text":["exencephaly"],"offsets":[[239,250]],"normalized":[{"db_name":"MESH","db_id":"D009436"}]},{"id":"22880","type":"Disease","text":["exencephaly"],"offsets":[[543,554]],"normalized":[{"db_name":"MESH","db_id":"D009436"}]},{"id":"22881","type":"Chemical","text":["5-azacytidine"],"offsets":[[566,579]],"normalized":[{"db_name":"MESH","db_id":"D001374"}]},{"id":"22882","type":"Disease","text":["exencephaly"],"offsets":[[751,762]],"normalized":[{"db_name":"MESH","db_id":"D009436"}]},{"id":"22883","type":"Disease","text":["anencephaly"],"offsets":[[766,777]],"normalized":[{"db_name":"MESH","db_id":"D000757"}]},{"id":"22884","type":"Disease","text":["exencephalic"],"offsets":[[807,819]],"normalized":[{"db_name":"MESH","db_id":"D009436"}]},{"id":"22885","type":"Disease","text":["exencephaly"],"offsets":[[953,964]],"normalized":[{"db_name":"MESH","db_id":"D009436"}]},{"id":"22886","type":"Disease","text":["exencephalic"],"offsets":[[990,1002]],"normalized":[{"db_name":"MESH","db_id":"D009436"}]},{"id":"22887","type":"Disease","text":["exencephalic"],"offsets":[[1089,1101]],"normalized":[{"db_name":"MESH","db_id":"D009436"}]},{"id":"22888","type":"Disease","text":["anencephaly"],"offsets":[[1157,1168]],"normalized":[{"db_name":"MESH","db_id":"D000757"}]},{"id":"22889","type":"Disease","text":["exencephalic"],"offsets":[[1223,1235]],"normalized":[{"db_name":"MESH","db_id":"D009436"}]},{"id":"22890","type":"Disease","text":["exencephaly"],"offsets":[[1305,1316]],"normalized":[{"db_name":"MESH","db_id":"D009436"}]},{"id":"22891","type":"Disease","text":["hemorrhaging"],"offsets":[[1336,1348]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"22892","type":"Disease","text":["exencephalic"],"offsets":[[1413,1425]],"normalized":[{"db_name":"MESH","db_id":"D009436"}]},{"id":"22893","type":"Disease","text":["exencephalic"],"offsets":[[1480,1492]],"normalized":[{"db_name":"MESH","db_id":"D009436"}]},{"id":"22894","type":"Disease","text":["exencephalic"],"offsets":[[1612,1624]],"normalized":[{"db_name":"MESH","db_id":"D009436"}]},{"id":"22895","type":"Disease","text":["exencephalic"],"offsets":[[1677,1689]],"normalized":[{"db_name":"MESH","db_id":"D009436"}]},{"id":"22896","type":"Disease","text":["circulatory failure"],"offsets":[[1779,1798]],"normalized":[{"db_name":"MESH","db_id":"D012769"}]},{"id":"22897","type":"Disease","text":["hemorrhaging"],"offsets":[[1806,1818]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"22898","type":"Disease","text":["exencephalic"],"offsets":[[1843,1855]],"normalized":[{"db_name":"MESH","db_id":"D009436"}]},{"id":"22899","type":"Disease","text":["exencephaly"],"offsets":[[1939,1950]],"normalized":[{"db_name":"MESH","db_id":"D009436"}]},{"id":"22900","type":"Disease","text":["anencephaly"],"offsets":[[1954,1965]],"normalized":[{"db_name":"MESH","db_id":"D000757"}]}],"events":[],"coreferences":[],"relations":[{"id":"22901","type":"CID","arg1_id":"22881","arg2_id":"22877","normalized":[]},{"id":"22902","type":"CID","arg1_id":"22881","arg2_id":"22878","normalized":[]},{"id":"22903","type":"CID","arg1_id":"22881","arg2_id":"22883","normalized":[]},{"id":"22904","type":"CID","arg1_id":"22881","arg2_id":"22888","normalized":[]},{"id":"22905","type":"CID","arg1_id":"22881","arg2_id":"22900","normalized":[]}]}
{"id":"22906","document_id":"11166519","passages":[{"id":"22907","type":"title","text":["Acute cocaine-induced seizures: differential sensitivity of six inbred mouse strains."],"offsets":[[0,85]]},{"id":"22908","type":"abstract","text":["Mature male and female mice from six inbred stains were tested for susceptibility to behavioral seizures induced by a single injection of cocaine. Cocaine was injected ip over a range of doses (50-100 mg\/kg) and behavior was monitored for 20 minutes. Seizure end points included latency to forelimb or hindlimb clonus, latency to clonic running seizure and latency to jumping bouncing seizure. A range of strain specific sensitivities was documented with A\/J and SJL mice being most sensitive and C57BL\/6J most resistant. DBA\/2J, BALB\/cByJ and NZW\/LacJ strains exhibited intermediate sensitivity. EEG recordings were made in SJL, A\/J and C57BL\/6J mice revealing a close correspondence between electrical activity and behavior. Additionally, levels of cocaine determined in hippocampus and cortex were not different between sensitive and resistant strains. Additional studies of these murine strains may be useful for investigating genetic influences on cocaine-induced seizures."],"offsets":[[86,1064]]}],"entities":[{"id":"22909","type":"Chemical","text":["cocaine"],"offsets":[[6,13]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"22910","type":"Disease","text":["seizures"],"offsets":[[22,30]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"22911","type":"Disease","text":["seizures"],"offsets":[[182,190]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"22912","type":"Chemical","text":["cocaine"],"offsets":[[224,231]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"22913","type":"Chemical","text":["Cocaine"],"offsets":[[233,240]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"22914","type":"Disease","text":["Seizure"],"offsets":[[337,344]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"22915","type":"Disease","text":["seizure"],"offsets":[[431,438]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"22916","type":"Disease","text":["seizure"],"offsets":[[471,478]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"22917","type":"Chemical","text":["cocaine"],"offsets":[[837,844]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"22918","type":"Chemical","text":["cocaine"],"offsets":[[1039,1046]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"22919","type":"Disease","text":["seizures"],"offsets":[[1055,1063]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]}],"events":[],"coreferences":[],"relations":[{"id":"22920","type":"CID","arg1_id":"22909","arg2_id":"22910","normalized":[]},{"id":"22921","type":"CID","arg1_id":"22909","arg2_id":"22911","normalized":[]},{"id":"22922","type":"CID","arg1_id":"22909","arg2_id":"22914","normalized":[]},{"id":"22923","type":"CID","arg1_id":"22909","arg2_id":"22915","normalized":[]},{"id":"22924","type":"CID","arg1_id":"22909","arg2_id":"22916","normalized":[]},{"id":"22925","type":"CID","arg1_id":"22909","arg2_id":"22919","normalized":[]},{"id":"22926","type":"CID","arg1_id":"22912","arg2_id":"22910","normalized":[]},{"id":"22927","type":"CID","arg1_id":"22912","arg2_id":"22911","normalized":[]},{"id":"22928","type":"CID","arg1_id":"22912","arg2_id":"22914","normalized":[]},{"id":"22929","type":"CID","arg1_id":"22912","arg2_id":"22915","normalized":[]},{"id":"22930","type":"CID","arg1_id":"22912","arg2_id":"22916","normalized":[]},{"id":"22931","type":"CID","arg1_id":"22912","arg2_id":"22919","normalized":[]},{"id":"22932","type":"CID","arg1_id":"22913","arg2_id":"22910","normalized":[]},{"id":"22933","type":"CID","arg1_id":"22913","arg2_id":"22911","normalized":[]},{"id":"22934","type":"CID","arg1_id":"22913","arg2_id":"22914","normalized":[]},{"id":"22935","type":"CID","arg1_id":"22913","arg2_id":"22915","normalized":[]},{"id":"22936","type":"CID","arg1_id":"22913","arg2_id":"22916","normalized":[]},{"id":"22937","type":"CID","arg1_id":"22913","arg2_id":"22919","normalized":[]},{"id":"22938","type":"CID","arg1_id":"22917","arg2_id":"22910","normalized":[]},{"id":"22939","type":"CID","arg1_id":"22917","arg2_id":"22911","normalized":[]},{"id":"22940","type":"CID","arg1_id":"22917","arg2_id":"22914","normalized":[]},{"id":"22941","type":"CID","arg1_id":"22917","arg2_id":"22915","normalized":[]},{"id":"22942","type":"CID","arg1_id":"22917","arg2_id":"22916","normalized":[]},{"id":"22943","type":"CID","arg1_id":"22917","arg2_id":"22919","normalized":[]},{"id":"22944","type":"CID","arg1_id":"22918","arg2_id":"22910","normalized":[]},{"id":"22945","type":"CID","arg1_id":"22918","arg2_id":"22911","normalized":[]},{"id":"22946","type":"CID","arg1_id":"22918","arg2_id":"22914","normalized":[]},{"id":"22947","type":"CID","arg1_id":"22918","arg2_id":"22915","normalized":[]},{"id":"22948","type":"CID","arg1_id":"22918","arg2_id":"22916","normalized":[]},{"id":"22949","type":"CID","arg1_id":"22918","arg2_id":"22919","normalized":[]}]}
{"id":"22950","document_id":"8701950","passages":[{"id":"22951","type":"title","text":["Microangiopathic hemolytic anemia complicating FK506 (tacrolimus) therapy."],"offsets":[[0,74]]},{"id":"22952","type":"abstract","text":["We describe 3 episodes of microangiopathic hemolytic anemia (MAHA) in 2 solid organ recipients under FK506 (tacrolimus) therapy. In both cases, discontinuation of FK506 and treatment with plasma exchange, fresh frozen plasma replacement, corticosteroids, aspirin, and dipyridamole led to resolution of MAHA. In one patient, reintroduction of FK506 led to rapid recurrence of MAHA. FK506-associated MAHA is probably rare but physicians must be aware of this severe complication. In our experience and according to the literature, FK506 does not seem to cross-react with cyclosporin A (CyA), an immuno-suppressive drug already known to induce MAHA."],"offsets":[[75,721]]}],"entities":[{"id":"22953","type":"Disease","text":["Microangiopathic hemolytic anemia"],"offsets":[[0,33]],"normalized":[{"db_name":"MESH","db_id":"D000743"}]},{"id":"22954","type":"Chemical","text":["FK506"],"offsets":[[47,52]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"22955","type":"Chemical","text":["tacrolimus"],"offsets":[[54,64]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"22956","type":"Disease","text":["microangiopathic hemolytic anemia"],"offsets":[[101,134]],"normalized":[{"db_name":"MESH","db_id":"D000743"}]},{"id":"22957","type":"Disease","text":["MAHA"],"offsets":[[136,140]],"normalized":[{"db_name":"MESH","db_id":"D000743"}]},{"id":"22958","type":"Chemical","text":["FK506"],"offsets":[[176,181]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"22959","type":"Chemical","text":["tacrolimus"],"offsets":[[183,193]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"22960","type":"Chemical","text":["FK506"],"offsets":[[238,243]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"22961","type":"Chemical","text":["corticosteroids"],"offsets":[[313,328]],"normalized":[{"db_name":"MESH","db_id":"D000305"}]},{"id":"22962","type":"Chemical","text":["aspirin"],"offsets":[[330,337]],"normalized":[{"db_name":"MESH","db_id":"D001241"}]},{"id":"22963","type":"Chemical","text":["dipyridamole"],"offsets":[[343,355]],"normalized":[{"db_name":"MESH","db_id":"D004176"}]},{"id":"22964","type":"Disease","text":["MAHA"],"offsets":[[377,381]],"normalized":[{"db_name":"MESH","db_id":"D000743"}]},{"id":"22965","type":"Chemical","text":["FK506"],"offsets":[[417,422]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"22966","type":"Disease","text":["MAHA"],"offsets":[[450,454]],"normalized":[{"db_name":"MESH","db_id":"D000743"}]},{"id":"22967","type":"Chemical","text":["FK506"],"offsets":[[456,461]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"22968","type":"Disease","text":["MAHA"],"offsets":[[473,477]],"normalized":[{"db_name":"MESH","db_id":"D000743"}]},{"id":"22969","type":"Chemical","text":["FK506"],"offsets":[[604,609]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"22970","type":"Chemical","text":["cyclosporin A"],"offsets":[[644,657]],"normalized":[{"db_name":"MESH","db_id":"D016572"}]},{"id":"22971","type":"Chemical","text":["CyA"],"offsets":[[659,662]],"normalized":[{"db_name":"MESH","db_id":"D016572"}]},{"id":"22972","type":"Disease","text":["MAHA"],"offsets":[[716,720]],"normalized":[{"db_name":"MESH","db_id":"D000743"}]}],"events":[],"coreferences":[],"relations":[{"id":"22973","type":"CID","arg1_id":"22954","arg2_id":"22953","normalized":[]},{"id":"22974","type":"CID","arg1_id":"22954","arg2_id":"22956","normalized":[]},{"id":"22975","type":"CID","arg1_id":"22954","arg2_id":"22957","normalized":[]},{"id":"22976","type":"CID","arg1_id":"22954","arg2_id":"22964","normalized":[]},{"id":"22977","type":"CID","arg1_id":"22954","arg2_id":"22966","normalized":[]},{"id":"22978","type":"CID","arg1_id":"22954","arg2_id":"22968","normalized":[]},{"id":"22979","type":"CID","arg1_id":"22954","arg2_id":"22972","normalized":[]},{"id":"22980","type":"CID","arg1_id":"22955","arg2_id":"22953","normalized":[]},{"id":"22981","type":"CID","arg1_id":"22955","arg2_id":"22956","normalized":[]},{"id":"22982","type":"CID","arg1_id":"22955","arg2_id":"22957","normalized":[]},{"id":"22983","type":"CID","arg1_id":"22955","arg2_id":"22964","normalized":[]},{"id":"22984","type":"CID","arg1_id":"22955","arg2_id":"22966","normalized":[]},{"id":"22985","type":"CID","arg1_id":"22955","arg2_id":"22968","normalized":[]},{"id":"22986","type":"CID","arg1_id":"22955","arg2_id":"22972","normalized":[]},{"id":"22987","type":"CID","arg1_id":"22958","arg2_id":"22953","normalized":[]},{"id":"22988","type":"CID","arg1_id":"22958","arg2_id":"22956","normalized":[]},{"id":"22989","type":"CID","arg1_id":"22958","arg2_id":"22957","normalized":[]},{"id":"22990","type":"CID","arg1_id":"22958","arg2_id":"22964","normalized":[]},{"id":"22991","type":"CID","arg1_id":"22958","arg2_id":"22966","normalized":[]},{"id":"22992","type":"CID","arg1_id":"22958","arg2_id":"22968","normalized":[]},{"id":"22993","type":"CID","arg1_id":"22958","arg2_id":"22972","normalized":[]},{"id":"22994","type":"CID","arg1_id":"22959","arg2_id":"22953","normalized":[]},{"id":"22995","type":"CID","arg1_id":"22959","arg2_id":"22956","normalized":[]},{"id":"22996","type":"CID","arg1_id":"22959","arg2_id":"22957","normalized":[]},{"id":"22997","type":"CID","arg1_id":"22959","arg2_id":"22964","normalized":[]},{"id":"22998","type":"CID","arg1_id":"22959","arg2_id":"22966","normalized":[]},{"id":"22999","type":"CID","arg1_id":"22959","arg2_id":"22968","normalized":[]},{"id":"23000","type":"CID","arg1_id":"22959","arg2_id":"22972","normalized":[]},{"id":"23001","type":"CID","arg1_id":"22960","arg2_id":"22953","normalized":[]},{"id":"23002","type":"CID","arg1_id":"22960","arg2_id":"22956","normalized":[]},{"id":"23003","type":"CID","arg1_id":"22960","arg2_id":"22957","normalized":[]},{"id":"23004","type":"CID","arg1_id":"22960","arg2_id":"22964","normalized":[]},{"id":"23005","type":"CID","arg1_id":"22960","arg2_id":"22966","normalized":[]},{"id":"23006","type":"CID","arg1_id":"22960","arg2_id":"22968","normalized":[]},{"id":"23007","type":"CID","arg1_id":"22960","arg2_id":"22972","normalized":[]},{"id":"23008","type":"CID","arg1_id":"22965","arg2_id":"22953","normalized":[]},{"id":"23009","type":"CID","arg1_id":"22965","arg2_id":"22956","normalized":[]},{"id":"23010","type":"CID","arg1_id":"22965","arg2_id":"22957","normalized":[]},{"id":"23011","type":"CID","arg1_id":"22965","arg2_id":"22964","normalized":[]},{"id":"23012","type":"CID","arg1_id":"22965","arg2_id":"22966","normalized":[]},{"id":"23013","type":"CID","arg1_id":"22965","arg2_id":"22968","normalized":[]},{"id":"23014","type":"CID","arg1_id":"22965","arg2_id":"22972","normalized":[]},{"id":"23015","type":"CID","arg1_id":"22967","arg2_id":"22953","normalized":[]},{"id":"23016","type":"CID","arg1_id":"22967","arg2_id":"22956","normalized":[]},{"id":"23017","type":"CID","arg1_id":"22967","arg2_id":"22957","normalized":[]},{"id":"23018","type":"CID","arg1_id":"22967","arg2_id":"22964","normalized":[]},{"id":"23019","type":"CID","arg1_id":"22967","arg2_id":"22966","normalized":[]},{"id":"23020","type":"CID","arg1_id":"22967","arg2_id":"22968","normalized":[]},{"id":"23021","type":"CID","arg1_id":"22967","arg2_id":"22972","normalized":[]},{"id":"23022","type":"CID","arg1_id":"22969","arg2_id":"22953","normalized":[]},{"id":"23023","type":"CID","arg1_id":"22969","arg2_id":"22956","normalized":[]},{"id":"23024","type":"CID","arg1_id":"22969","arg2_id":"22957","normalized":[]},{"id":"23025","type":"CID","arg1_id":"22969","arg2_id":"22964","normalized":[]},{"id":"23026","type":"CID","arg1_id":"22969","arg2_id":"22966","normalized":[]},{"id":"23027","type":"CID","arg1_id":"22969","arg2_id":"22968","normalized":[]},{"id":"23028","type":"CID","arg1_id":"22969","arg2_id":"22972","normalized":[]}]}
{"id":"23029","document_id":"7292072","passages":[{"id":"23030","type":"title","text":["Variant ventricular tachycardia in desipramine toxicity."],"offsets":[[0,56]]},{"id":"23031","type":"abstract","text":["We report a case of variant ventricular tachycardia induced by desipramine toxicity. Unusual features of the arrhythmia are repetitive group beating, progressive shortening of the R-R interval, progressive widening of the QRS complex with eventual failure of intraventricular conduction, and changes in direction of the QRS axis. Recognition of variant ventricular tachycardia is important because therapy differs from that of classic ventricular tachycardia."],"offsets":[[57,516]]}],"entities":[{"id":"23032","type":"Disease","text":["ventricular tachycardia"],"offsets":[[8,31]],"normalized":[{"db_name":"MESH","db_id":"D017180"}]},{"id":"23033","type":"Chemical","text":["desipramine"],"offsets":[[35,46]],"normalized":[{"db_name":"MESH","db_id":"D003891"}]},{"id":"23034","type":"Disease","text":["toxicity"],"offsets":[[47,55]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"23035","type":"Disease","text":["ventricular tachycardia"],"offsets":[[85,108]],"normalized":[{"db_name":"MESH","db_id":"D017180"}]},{"id":"23036","type":"Chemical","text":["desipramine"],"offsets":[[120,131]],"normalized":[{"db_name":"MESH","db_id":"D003891"}]},{"id":"23037","type":"Disease","text":["toxicity"],"offsets":[[132,140]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"23038","type":"Disease","text":["arrhythmia"],"offsets":[[166,176]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"23039","type":"Disease","text":["ventricular tachycardia"],"offsets":[[410,433]],"normalized":[{"db_name":"MESH","db_id":"D017180"}]},{"id":"23040","type":"Disease","text":["ventricular tachycardia"],"offsets":[[492,515]],"normalized":[{"db_name":"MESH","db_id":"D017180"}]}],"events":[],"coreferences":[],"relations":[{"id":"23041","type":"CID","arg1_id":"23033","arg2_id":"23032","normalized":[]},{"id":"23042","type":"CID","arg1_id":"23033","arg2_id":"23035","normalized":[]},{"id":"23043","type":"CID","arg1_id":"23033","arg2_id":"23039","normalized":[]},{"id":"23044","type":"CID","arg1_id":"23033","arg2_id":"23040","normalized":[]},{"id":"23045","type":"CID","arg1_id":"23036","arg2_id":"23032","normalized":[]},{"id":"23046","type":"CID","arg1_id":"23036","arg2_id":"23035","normalized":[]},{"id":"23047","type":"CID","arg1_id":"23036","arg2_id":"23039","normalized":[]},{"id":"23048","type":"CID","arg1_id":"23036","arg2_id":"23040","normalized":[]}]}
{"id":"23049","document_id":"4027862","passages":[{"id":"23050","type":"title","text":["Desipramine-induced delirium at \"subtherapeutic\" concentrations: a case report."],"offsets":[[0,79]]},{"id":"23051","type":"abstract","text":["An elderly patient treated with low dose Desipramine developed a delirium while her plasma level was in the \"subtherapeutic\" range. Delirium, which may be induced by tricyclic drug therapy in the elderly, can be caused by tricyclics with low anticholinergic potency. Therapeutic ranges for antidepressants that have been derived from general adult population studies may not be appropriate for the elderly. Further studies of specifically elderly patients are now required to establish safer and more appropriate guidelines for drug therapy."],"offsets":[[80,621]]}],"entities":[{"id":"23052","type":"Chemical","text":["Desipramine"],"offsets":[[0,11]],"normalized":[{"db_name":"MESH","db_id":"D003891"}]},{"id":"23053","type":"Disease","text":["delirium"],"offsets":[[20,28]],"normalized":[{"db_name":"MESH","db_id":"D003693"}]},{"id":"23054","type":"Chemical","text":["Desipramine"],"offsets":[[121,132]],"normalized":[{"db_name":"MESH","db_id":"D003891"}]},{"id":"23055","type":"Disease","text":["delirium"],"offsets":[[145,153]],"normalized":[{"db_name":"MESH","db_id":"D003693"}]},{"id":"23056","type":"Disease","text":["Delirium"],"offsets":[[212,220]],"normalized":[{"db_name":"MESH","db_id":"D003693"}]},{"id":"23057","type":"Chemical","text":["antidepressants"],"offsets":[[370,385]],"normalized":[{"db_name":"MESH","db_id":"D000928"}]}],"events":[],"coreferences":[],"relations":[{"id":"23058","type":"CID","arg1_id":"23052","arg2_id":"23053","normalized":[]},{"id":"23059","type":"CID","arg1_id":"23052","arg2_id":"23055","normalized":[]},{"id":"23060","type":"CID","arg1_id":"23052","arg2_id":"23056","normalized":[]},{"id":"23061","type":"CID","arg1_id":"23054","arg2_id":"23053","normalized":[]},{"id":"23062","type":"CID","arg1_id":"23054","arg2_id":"23055","normalized":[]},{"id":"23063","type":"CID","arg1_id":"23054","arg2_id":"23056","normalized":[]}]}
{"id":"23064","document_id":"2484011","passages":[{"id":"23065","type":"title","text":["Mouse strain-dependent effect of amantadine on motility and brain biogenic amines."],"offsets":[[0,82]]},{"id":"23066","type":"abstract","text":["The effect of amantadine hydrochloride, injected i.p. in 6 increments of 100 mg\/kg each over 30 hr, on mouse motility and whole brain content of selected biogenic amines and major metabolites was studied in 4 strains of mice. These were the albino Sprague-Dawley ICR and BALB\/C, the black C57BL\/6 and the brown CDF-I mouse strains. Amantadine treatment produced a biphasic effect on mouse motility. The initial dose of amantadine depressed locomotor activity in all mouse strains studied with the BALB\/C mice being the most sensitive. Subsequent amantadine treatments produced enhancement of motility from corresponding control in all mouse strains with the BALB\/C mice being the least sensitive. The locomotor activity was decreased from corresponding controls in all strains studied, except for the ICR mice, during an overnight drug-free period following the fourth amantadine treatment. Readministration of amantadine, after a drug-free overnight period, increased motility from respective saline control in all strains with exception of the BALB\/C mice where suppression of motility occurred. Treatment with amantadine did not alter whole brain dopamine levels but decreased the amounts of 3,4-dihydroxyphenylacetic acid in the BALB\/C mice compared to saline control. Conversely, brain normetanephrine concentration was increased from saline control by amantadine in the BALB\/C mice. The results suggest a strain-dependent effect of amantadine on motility and indicate a differential response to the acute and multiple dose regimens used. The BALB\/C mouse was the most sensitive strain and could serve as the strain of choice for evaluating the side effects of amantadine. The biochemical results of brain biogenic amines of BALB\/C mouse strain suggest a probable decrease of catecholamine turnover rate and\/or metabolism by monoamine oxidase and a resulting increase in O-methylation of norepinephrine which may account for a behavioral depression caused by amantadine in the BALB\/C mice."],"offsets":[[83,2077]]}],"entities":[{"id":"23067","type":"Chemical","text":["amantadine"],"offsets":[[33,43]],"normalized":[{"db_name":"MESH","db_id":"D000547"}]},{"id":"23068","type":"Chemical","text":["amines"],"offsets":[[75,81]],"normalized":[{"db_name":"MESH","db_id":"D000588"}]},{"id":"23069","type":"Chemical","text":["amantadine hydrochloride"],"offsets":[[97,121]],"normalized":[{"db_name":"MESH","db_id":"D000547"}]},{"id":"23070","type":"Chemical","text":["amines"],"offsets":[[246,252]],"normalized":[{"db_name":"MESH","db_id":"D000588"}]},{"id":"23071","type":"Chemical","text":["Amantadine"],"offsets":[[415,425]],"normalized":[{"db_name":"MESH","db_id":"D000547"}]},{"id":"23072","type":"Chemical","text":["amantadine"],"offsets":[[502,512]],"normalized":[{"db_name":"MESH","db_id":"D000547"}]},{"id":"23073","type":"Disease","text":["depressed"],"offsets":[[513,522]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"23074","type":"Chemical","text":["amantadine"],"offsets":[[629,639]],"normalized":[{"db_name":"MESH","db_id":"D000547"}]},{"id":"23075","type":"Chemical","text":["amantadine"],"offsets":[[952,962]],"normalized":[{"db_name":"MESH","db_id":"D000547"}]},{"id":"23076","type":"Chemical","text":["amantadine"],"offsets":[[994,1004]],"normalized":[{"db_name":"MESH","db_id":"D000547"}]},{"id":"23077","type":"Disease","text":["suppression of motility"],"offsets":[[1147,1170]],"normalized":[{"db_name":"MESH","db_id":"D011596"}]},{"id":"23078","type":"Chemical","text":["amantadine"],"offsets":[[1196,1206]],"normalized":[{"db_name":"MESH","db_id":"D000547"}]},{"id":"23079","type":"Chemical","text":["dopamine"],"offsets":[[1233,1241]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"23080","type":"Chemical","text":["3,4-dihydroxyphenylacetic 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depression"],"offsets":[[2015,2036]],"normalized":[{"db_name":"MESH","db_id":"D011596"}]},{"id":"23089","type":"Chemical","text":["amantadine"],"offsets":[[2047,2057]],"normalized":[{"db_name":"MESH","db_id":"D000547"}]}],"events":[],"coreferences":[],"relations":[{"id":"23090","type":"CID","arg1_id":"23067","arg2_id":"23077","normalized":[]},{"id":"23091","type":"CID","arg1_id":"23067","arg2_id":"23088","normalized":[]},{"id":"23092","type":"CID","arg1_id":"23069","arg2_id":"23077","normalized":[]},{"id":"23093","type":"CID","arg1_id":"23069","arg2_id":"23088","normalized":[]},{"id":"23094","type":"CID","arg1_id":"23071","arg2_id":"23077","normalized":[]},{"id":"23095","type":"CID","arg1_id":"23071","arg2_id":"23088","normalized":[]},{"id":"23096","type":"CID","arg1_id":"23072","arg2_id":"23077","normalized":[]},{"id":"23097","type":"CID","arg1_id":"23072","arg2_id":"23088","normalized":[]},{"id":"23098","type":"CID","arg1_id":"23074","arg2_id":"23077","normalized":[]},{"id":"23099","type":"CID","arg1_id":"23074","arg2_id":"23088","normalized":[]},{"id":"23100","type":"CID","arg1_id":"23075","arg2_id":"23077","normalized":[]},{"id":"23101","type":"CID","arg1_id":"23075","arg2_id":"23088","normalized":[]},{"id":"23102","type":"CID","arg1_id":"23076","arg2_id":"23077","normalized":[]},{"id":"23103","type":"CID","arg1_id":"23076","arg2_id":"23088","normalized":[]},{"id":"23104","type":"CID","arg1_id":"23078","arg2_id":"23077","normalized":[]},{"id":"23105","type":"CID","arg1_id":"23078","arg2_id":"23088","normalized":[]},{"id":"23106","type":"CID","arg1_id":"23082","arg2_id":"23077","normalized":[]},{"id":"23107","type":"CID","arg1_id":"23082","arg2_id":"23088","normalized":[]},{"id":"23108","type":"CID","arg1_id":"23083","arg2_id":"23077","normalized":[]},{"id":"23109","type":"CID","arg1_id":"23083","arg2_id":"23088","normalized":[]},{"id":"23110","type":"CID","arg1_id":"23084","arg2_id":"23077","normalized":[]},{"id":"23111","type":"CID","arg1_id":"23084","arg2_id":"23088","normalized":[]},{"id":"23112","type":"CID","arg1_id":"23089","arg2_id":"23077","normalized":[]},{"id":"23113","type":"CID","arg1_id":"23089","arg2_id":"23088","normalized":[]}]}
{"id":"23114","document_id":"2396046","passages":[{"id":"23115","type":"title","text":["No enhancement by phenobarbital of the hepatocarcinogenicity of a choline-devoid diet in the rat."],"offsets":[[0,97]]},{"id":"23116","type":"abstract","text":["An experiment was performed to test whether inclusion of phenobarbital in a choline-devoid diet would increase the hepatocarcinogenicity of the diet. Groups of 5-week old male Fischer-344 rats were fed for 7-25 months semipurified choline-devoid or choline-supplemented diets, containing or not 0.06% phenobarbital. No hepatic preneoplastic nodules or hepatocellular carcinomas developed in rats fed the plain choline-supplemented diet, while one preneoplastic nodule and one hepatocellular carcinoma developed in two rats fed the same diet containing phenobarbital. The incidence of preneoplastic nodules and of hepatocellular carcinomas was 10% and 37%, respectively, in rats fed the plain choline-devoid diet, and 17% and 30%, in rats fed the phenobarbital-containing choline-devoid diet. The results evinced no enhancement of the hepatocarcinogenicity of the choline-devoid diet by phenobarbital. Sporadic neoplastic lesions were observed in organs other than the liver of some of the animals, irrespective of the diet fed."],"offsets":[[98,1125]]}],"entities":[{"id":"23117","type":"Chemical","text":["phenobarbital"],"offsets":[[18,31]],"normalized":[{"db_name":"MESH","db_id":"D010634"}]},{"id":"23118","type":"Chemical","text":["choline"],"offsets":[[66,73]],"normalized":[{"db_name":"MESH","db_id":"D002794"}]},{"id":"23119","type":"Chemical","text":["phenobarbital"],"offsets":[[155,168]],"normalized":[{"db_name":"MESH","db_id":"D010634"}]},{"id":"23120","type":"Chemical","text":["choline"],"offsets":[[174,181]],"normalized":[{"db_name":"MESH","db_id":"D002794"}]},{"id":"23121","type":"Chemical","text":["choline"],"offsets":[[329,336]],"normalized":[{"db_name":"MESH","db_id":"D002794"}]},{"id":"23122","type":"Chemical","text":["choline"],"offsets":[[347,354]],"normalized":[{"db_name":"MESH","db_id":"D002794"}]},{"id":"23123","type":"Chemical","text":["phenobarbital"],"offsets":[[399,412]],"normalized":[{"db_name":"MESH","db_id":"D010634"}]},{"id":"23124","type":"Disease","text":["hepatocellular carcinomas"],"offsets":[[450,475]],"normalized":[{"db_name":"MESH","db_id":"D006528"}]},{"id":"23125","type":"Chemical","text":["choline"],"offsets":[[508,515]],"normalized":[{"db_name":"MESH","db_id":"D002794"}]},{"id":"23126","type":"Disease","text":["hepatocellular carcinoma"],"offsets":[[574,598]],"normalized":[{"db_name":"MESH","db_id":"D006528"}]},{"id":"23127","type":"Chemical","text":["phenobarbital"],"offsets":[[650,663]],"normalized":[{"db_name":"MESH","db_id":"D010634"}]},{"id":"23128","type":"Disease","text":["hepatocellular carcinomas"],"offsets":[[711,736]],"normalized":[{"db_name":"MESH","db_id":"D006528"}]},{"id":"23129","type":"Chemical","text":["choline"],"offsets":[[790,797]],"normalized":[{"db_name":"MESH","db_id":"D002794"}]},{"id":"23130","type":"Chemical","text":["phenobarbital"],"offsets":[[844,857]],"normalized":[{"db_name":"MESH","db_id":"D010634"}]},{"id":"23131","type":"Chemical","text":["choline"],"offsets":[[869,876]],"normalized":[{"db_name":"MESH","db_id":"D002794"}]},{"id":"23132","type":"Chemical","text":["choline"],"offsets":[[961,968]],"normalized":[{"db_name":"MESH","db_id":"D002794"}]},{"id":"23133","type":"Chemical","text":["phenobarbital"],"offsets":[[984,997]],"normalized":[{"db_name":"MESH","db_id":"D010634"}]}],"events":[],"coreferences":[],"relations":[{"id":"23134","type":"CID","arg1_id":"23118","arg2_id":"23124","normalized":[]},{"id":"23135","type":"CID","arg1_id":"23118","arg2_id":"23126","normalized":[]},{"id":"23136","type":"CID","arg1_id":"23118","arg2_id":"23128","normalized":[]},{"id":"23137","type":"CID","arg1_id":"23120","arg2_id":"23124","normalized":[]},{"id":"23138","type":"CID","arg1_id":"23120","arg2_id":"23126","normalized":[]},{"id":"23139","type":"CID","arg1_id":"23120","arg2_id":"23128","normalized":[]},{"id":"23140","type":"CID","arg1_id":"23121","arg2_id":"23124","normalized":[]},{"id":"23141","type":"CID","arg1_id":"23121","arg2_id":"23126","normalized":[]},{"id":"23142","type":"CID","arg1_id":"23121","arg2_id":"23128","normalized":[]},{"id":"23143","type":"CID","arg1_id":"23122","arg2_id":"23124","normalized":[]},{"id":"23144","type":"CID","arg1_id":"23122","arg2_id":"23126","normalized":[]},{"id":"23145","type":"CID","arg1_id":"23122","arg2_id":"23128","normalized":[]},{"id":"23146","type":"CID","arg1_id":"23125","arg2_id":"23124","normalized":[]},{"id":"23147","type":"CID","arg1_id":"23125","arg2_id":"23126","normalized":[]},{"id":"23148","type":"CID","arg1_id":"23125","arg2_id":"23128","normalized":[]},{"id":"23149","type":"CID","arg1_id":"23129","arg2_id":"23124","normalized":[]},{"id":"23150","type":"CID","arg1_id":"23129","arg2_id":"23126","normalized":[]},{"id":"23151","type":"CID","arg1_id":"23129","arg2_id":"23128","normalized":[]},{"id":"23152","type":"CID","arg1_id":"23131","arg2_id":"23124","normalized":[]},{"id":"23153","type":"CID","arg1_id":"23131","arg2_id":"23126","normalized":[]},{"id":"23154","type":"CID","arg1_id":"23131","arg2_id":"23128","normalized":[]},{"id":"23155","type":"CID","arg1_id":"23132","arg2_id":"23124","normalized":[]},{"id":"23156","type":"CID","arg1_id":"23132","arg2_id":"23126","normalized":[]},{"id":"23157","type":"CID","arg1_id":"23132","arg2_id":"23128","normalized":[]}]}
{"id":"23158","document_id":"2008831","passages":[{"id":"23159","type":"title","text":["Effect of direct intracoronary administration of methylergonovine in patients with and without variant angina."],"offsets":[[0,110]]},{"id":"23160","type":"abstract","text":["The effects of intracoronary administration of methylergonovine were studied in 21 patients with variant angina and 22 patients with atypical chest pain and in others without angina pectoris (control group). Methylergonovine was administered continuously at a rate of 10 micrograms\/min up to 50 micrograms. In all patients with variant angina, coronary spasm was provoked at a mean dose of 28 +\/- 13 micrograms (mean +\/- SD). In the control group neither ischemic ST change nor localized spasm occurred. The basal tone of the right coronary artery was significantly lower than that of the left coronary artery. The percentage of vasoconstriction of the right coronary artery was significantly higher than that of the left coronary artery. These results suggest that spasm provocation tests, which use an intracoronary injection of a relatively low dose of methylergonovine, have a high sensitivity in variant angina and the vasoreactivity of the right coronary artery may be greater than that of the other coronary arteries."],"offsets":[[111,1135]]}],"entities":[{"id":"23161","type":"Chemical","text":["methylergonovine"],"offsets":[[49,65]],"normalized":[{"db_name":"MESH","db_id":"D008755"}]},{"id":"23162","type":"Disease","text":["variant angina"],"offsets":[[95,109]],"normalized":[{"db_name":"MESH","db_id":"D000788"}]},{"id":"23163","type":"Chemical","text":["methylergonovine"],"offsets":[[158,174]],"normalized":[{"db_name":"MESH","db_id":"D008755"}]},{"id":"23164","type":"Disease","text":["variant angina"],"offsets":[[208,222]],"normalized":[{"db_name":"MESH","db_id":"D000788"}]},{"id":"23165","type":"Disease","text":["chest pain"],"offsets":[[253,263]],"normalized":[{"db_name":"MESH","db_id":"D002637"}]},{"id":"23166","type":"Disease","text":["angina pectoris"],"offsets":[[286,301]],"normalized":[{"db_name":"MESH","db_id":"D000787"}]},{"id":"23167","type":"Chemical","text":["Methylergonovine"],"offsets":[[319,335]],"normalized":[{"db_name":"MESH","db_id":"D008755"}]},{"id":"23168","type":"Disease","text":["variant angina"],"offsets":[[439,453]],"normalized":[{"db_name":"MESH","db_id":"D000788"}]},{"id":"23169","type":"Disease","text":["coronary spasm"],"offsets":[[455,469]],"normalized":[{"db_name":"MESH","db_id":"D003329"}]},{"id":"23170","type":"Disease","text":["spasm"],"offsets":[[599,604]],"normalized":[{"db_name":"MESH","db_id":"D013035"}]},{"id":"23171","type":"Disease","text":["spasm"],"offsets":[[877,882]],"normalized":[{"db_name":"MESH","db_id":"D013035"}]},{"id":"23172","type":"Chemical","text":["methylergonovine"],"offsets":[[967,983]],"normalized":[{"db_name":"MESH","db_id":"D008755"}]},{"id":"23173","type":"Disease","text":["variant angina"],"offsets":[[1012,1026]],"normalized":[{"db_name":"MESH","db_id":"D000788"}]}],"events":[],"coreferences":[],"relations":[{"id":"23174","type":"CID","arg1_id":"23161","arg2_id":"23169","normalized":[]},{"id":"23175","type":"CID","arg1_id":"23163","arg2_id":"23169","normalized":[]},{"id":"23176","type":"CID","arg1_id":"23167","arg2_id":"23169","normalized":[]},{"id":"23177","type":"CID","arg1_id":"23172","arg2_id":"23169","normalized":[]}]}
{"id":"23178","document_id":"1732369","passages":[{"id":"23179","type":"title","text":["Dobutamine stress echocardiography: a sensitive indicator of diminished myocardial function in asymptomatic doxorubicin-treated long-term survivors of childhood cancer."],"offsets":[[0,168]]},{"id":"23180","type":"abstract","text":["Doxorubicin is an effective anticancer chemotherapeutic agent known to cause acute and chronic cardiomyopathy. To develop a more sensitive echocardiographic screening test for cardiac damage due to doxorubicin, a cohort study was performed using dobutamine infusion to differentiate asymptomatic long-term survivors of childhood cancer treated with doxorubicin from healthy control subjects. Echocardiographic data from the experimental group of 21 patients (mean age 16 +\/- 5 years) treated from 1.6 to 14.3 years (median 5.3) before this study with 27 to 532 mg\/m2 of doxorubicin (mean 196) were compared with echocardiographic data from 12 normal age-matched control subjects. Graded dobutamine infusions of 0.5, 2.5, 5 and 10 micrograms\/kg per min were administered. Echocardiographic Doppler studies were performed before infusion and after 15 min of infusion at each rate. Dobutamine infusion at 10 micrograms\/kg per min was discontinued after six studies secondary to a 50% incidence rate of adverse symptoms. The most important findings were that compared with values in control subjects, end-systolic left ventricular posterior wall dimension and percent of left ventricular posterior wall thickening in doxorubicin-treated patients were decreased at baseline study and these findings were more clearly delineated with dobutamine stimulation. End-systolic left ventricular posterior wall dimension at baseline for the doxorubicin-treated group was 11 +\/- 1.9 mm versus 13.1 +\/- 1.5 mm for control subjects (p less than 0.01). End-systolic left ventricular posterior wall dimension at the 5-micrograms\/kg per min dobutamine infusion for the doxorubicin-treated group was 14.1 +\/- 2.4 mm versus 19.3 +\/- 2.6 mm for control subjects (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)"],"offsets":[[169,1960]]}],"entities":[{"id":"23181","type":"Chemical","text":["Dobutamine"],"offsets":[[0,10]],"normalized":[{"db_name":"MESH","db_id":"D004280"}]},{"id":"23182","type":"Chemical","text":["doxorubicin"],"offsets":[[108,119]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"23183","type":"Disease","text":["cancer"],"offsets":[[161,167]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"23184","type":"Chemical","text":["Doxorubicin"],"offsets":[[169,180]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"23185","type":"Disease","text":["cardiomyopathy"],"offsets":[[264,278]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"23186","type":"Disease","text":["cardiac damage"],"offsets":[[345,359]],"normalized":[{"db_name":"MESH","db_id":"D006331"}]},{"id":"23187","type":"Chemical","text":["doxorubicin"],"offsets":[[367,378]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"23188","type":"Chemical","text":["dobutamine"],"offsets":[[415,425]],"normalized":[{"db_name":"MESH","db_id":"D004280"}]},{"id":"23189","type":"Disease","text":["cancer"],"offsets":[[498,504]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"23190","type":"Chemical","text":["doxorubicin"],"offsets":[[518,529]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"23191","type":"Chemical","text":["doxorubicin"],"offsets":[[739,750]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"23192","type":"Chemical","text":["dobutamine"],"offsets":[[856,866]],"normalized":[{"db_name":"MESH","db_id":"D004280"}]},{"id":"23193","type":"Chemical","text":["Dobutamine"],"offsets":[[1048,1058]],"normalized":[{"db_name":"MESH","db_id":"D004280"}]},{"id":"23194","type":"Chemical","text":["doxorubicin"],"offsets":[[1382,1393]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"23195","type":"Chemical","text":["dobutamine"],"offsets":[[1497,1507]],"normalized":[{"db_name":"MESH","db_id":"D004280"}]},{"id":"23196","type":"Chemical","text":["doxorubicin"],"offsets":[[1596,1607]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"23197","type":"Chemical","text":["dobutamine"],"offsets":[[1790,1800]],"normalized":[{"db_name":"MESH","db_id":"D004280"}]},{"id":"23198","type":"Chemical","text":["doxorubicin"],"offsets":[[1818,1829]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]}],"events":[],"coreferences":[],"relations":[{"id":"23199","type":"CID","arg1_id":"23182","arg2_id":"23185","normalized":[]},{"id":"23200","type":"CID","arg1_id":"23184","arg2_id":"23185","normalized":[]},{"id":"23201","type":"CID","arg1_id":"23187","arg2_id":"23185","normalized":[]},{"id":"23202","type":"CID","arg1_id":"23190","arg2_id":"23185","normalized":[]},{"id":"23203","type":"CID","arg1_id":"23191","arg2_id":"23185","normalized":[]},{"id":"23204","type":"CID","arg1_id":"23194","arg2_id":"23185","normalized":[]},{"id":"23205","type":"CID","arg1_id":"23196","arg2_id":"23185","normalized":[]},{"id":"23206","type":"CID","arg1_id":"23198","arg2_id":"23185","normalized":[]}]}
{"id":"23207","document_id":"234669","passages":[{"id":"23208","type":"title","text":["Effects of aminophylline on the threshold for initiating ventricular fibrillation during respiratory failure."],"offsets":[[0,109]]},{"id":"23209","type":"abstract","text":["Cardiac arrhythmias have frequently been reported in association with respiratory failure. The possible additive role of pharmacologic agents in precipitating cardiac disturbances in patients with respiratory failure has only recently been emphasized. The effects of aminophylline on the ventricular fibrillation threshold during normal acid-base conditions and during respiratory failure were studied in anesthetized open chest dogs. The ventricular fibrillation threshold was measured by passing a gated train of 12 constant current pulses through the ventricular myocardium during the vulnerable period of the cardiac cycle. During the infusion of aminophylline, the ventricular fibrillation threshold was reduced by 30 to 40 percent of the control when pH and partial pressures of oxygen (PO2) and carbon dioxide (CO2) were kept within normal limits. When respiratory failure was produced by hypoventilation (pH 7.05 to 7.25; PC02 70 to 100 mm Hg: P02 20 to 40 mm Hg), infusion of aminophylline resulted in an even greater decrease in ventricular fibrillation threshold to 60 percent of the control level. These experiments suggest that although many factors may contribute to the increased incidence of ventricular arrhythmias in respiratory failure, pharmacologic agents, particularly aminophylline, may play a significant role."],"offsets":[[110,1444]]}],"entities":[{"id":"23210","type":"Chemical","text":["aminophylline"],"offsets":[[11,24]],"normalized":[{"db_name":"MESH","db_id":"D000628"}]},{"id":"23211","type":"Disease","text":["ventricular fibrillation"],"offsets":[[57,81]],"normalized":[{"db_name":"MESH","db_id":"D014693"}]},{"id":"23212","type":"Disease","text":["respiratory failure"],"offsets":[[89,108]],"normalized":[{"db_name":"MESH","db_id":"D012131"}]},{"id":"23213","type":"Disease","text":["Cardiac arrhythmias"],"offsets":[[110,129]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"23214","type":"Disease","text":["respiratory failure"],"offsets":[[180,199]],"normalized":[{"db_name":"MESH","db_id":"D012131"}]},{"id":"23215","type":"Disease","text":["cardiac disturbances"],"offsets":[[269,289]],"normalized":[{"db_name":"MESH","db_id":"D006331"}]},{"id":"23216","type":"Disease","text":["respiratory failure"],"offsets":[[307,326]],"normalized":[{"db_name":"MESH","db_id":"D012131"}]},{"id":"23217","type":"Chemical","text":["aminophylline"],"offsets":[[377,390]],"normalized":[{"db_name":"MESH","db_id":"D000628"}]},{"id":"23218","type":"Disease","text":["ventricular fibrillation"],"offsets":[[398,422]],"normalized":[{"db_name":"MESH","db_id":"D014693"}]},{"id":"23219","type":"Disease","text":["respiratory failure"],"offsets":[[479,498]],"normalized":[{"db_name":"MESH","db_id":"D012131"}]},{"id":"23220","type":"Disease","text":["ventricular fibrillation"],"offsets":[[549,573]],"normalized":[{"db_name":"MESH","db_id":"D014693"}]},{"id":"23221","type":"Chemical","text":["aminophylline"],"offsets":[[761,774]],"normalized":[{"db_name":"MESH","db_id":"D000628"}]},{"id":"23222","type":"Disease","text":["ventricular fibrillation"],"offsets":[[780,804]],"normalized":[{"db_name":"MESH","db_id":"D014693"}]},{"id":"23223","type":"Chemical","text":["oxygen"],"offsets":[[895,901]],"normalized":[{"db_name":"MESH","db_id":"D010100"}]},{"id":"23224","type":"Chemical","text":["PO2"],"offsets":[[903,906]],"normalized":[{"db_name":"MESH","db_id":"C093415"}]},{"id":"23225","type":"Chemical","text":["carbon dioxide"],"offsets":[[912,926]],"normalized":[{"db_name":"MESH","db_id":"D002245"}]},{"id":"23226","type":"Chemical","text":["CO2"],"offsets":[[928,931]],"normalized":[{"db_name":"MESH","db_id":"D002245"}]},{"id":"23227","type":"Disease","text":["respiratory failure"],"offsets":[[970,989]],"normalized":[{"db_name":"MESH","db_id":"D012131"}]},{"id":"23228","type":"Disease","text":["hypoventilation"],"offsets":[[1006,1021]],"normalized":[{"db_name":"MESH","db_id":"D007040"}]},{"id":"23229","type":"Chemical","text":["aminophylline"],"offsets":[[1095,1108]],"normalized":[{"db_name":"MESH","db_id":"D000628"}]},{"id":"23230","type":"Disease","text":["ventricular fibrillation"],"offsets":[[1149,1173]],"normalized":[{"db_name":"MESH","db_id":"D014693"}]},{"id":"23231","type":"Disease","text":["ventricular arrhythmias"],"offsets":[[1318,1341]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"23232","type":"Disease","text":["respiratory failure"],"offsets":[[1345,1364]],"normalized":[{"db_name":"MESH","db_id":"D012131"}]},{"id":"23233","type":"Chemical","text":["aminophylline"],"offsets":[[1401,1414]],"normalized":[{"db_name":"MESH","db_id":"D000628"}]}],"events":[],"coreferences":[],"relations":[{"id":"23234","type":"CID","arg1_id":"23210","arg2_id":"23211","normalized":[]},{"id":"23235","type":"CID","arg1_id":"23210","arg2_id":"23218","normalized":[]},{"id":"23236","type":"CID","arg1_id":"23210","arg2_id":"23220","normalized":[]},{"id":"23237","type":"CID","arg1_id":"23210","arg2_id":"23222","normalized":[]},{"id":"23238","type":"CID","arg1_id":"23210","arg2_id":"23230","normalized":[]},{"id":"23239","type":"CID","arg1_id":"23217","arg2_id":"23211","normalized":[]},{"id":"23240","type":"CID","arg1_id":"23217","arg2_id":"23218","normalized":[]},{"id":"23241","type":"CID","arg1_id":"23217","arg2_id":"23220","normalized":[]},{"id":"23242","type":"CID","arg1_id":"23217","arg2_id":"23222","normalized":[]},{"id":"23243","type":"CID","arg1_id":"23217","arg2_id":"23230","normalized":[]},{"id":"23244","type":"CID","arg1_id":"23221","arg2_id":"23211","normalized":[]},{"id":"23245","type":"CID","arg1_id":"23221","arg2_id":"23218","normalized":[]},{"id":"23246","type":"CID","arg1_id":"23221","arg2_id":"23220","normalized":[]},{"id":"23247","type":"CID","arg1_id":"23221","arg2_id":"23222","normalized":[]},{"id":"23248","type":"CID","arg1_id":"23221","arg2_id":"23230","normalized":[]},{"id":"23249","type":"CID","arg1_id":"23229","arg2_id":"23211","normalized":[]},{"id":"23250","type":"CID","arg1_id":"23229","arg2_id":"23218","normalized":[]},{"id":"23251","type":"CID","arg1_id":"23229","arg2_id":"23220","normalized":[]},{"id":"23252","type":"CID","arg1_id":"23229","arg2_id":"23222","normalized":[]},{"id":"23253","type":"CID","arg1_id":"23229","arg2_id":"23230","normalized":[]},{"id":"23254","type":"CID","arg1_id":"23233","arg2_id":"23211","normalized":[]},{"id":"23255","type":"CID","arg1_id":"23233","arg2_id":"23218","normalized":[]},{"id":"23256","type":"CID","arg1_id":"23233","arg2_id":"23220","normalized":[]},{"id":"23257","type":"CID","arg1_id":"23233","arg2_id":"23222","normalized":[]},{"id":"23258","type":"CID","arg1_id":"23233","arg2_id":"23230","normalized":[]}]}
{"id":"23259","document_id":"16740173","passages":[{"id":"23260","type":"title","text":["Case report: acute unintentional carbachol intoxication."],"offsets":[[0,56]]},{"id":"23261","type":"abstract","text":["INTRODUCTION: Intoxications with carbachol, a muscarinic cholinergic receptor agonist are rare. We report an interesting case investigating a (near) fatal poisoning. METHODS: The son of an 84-year-old male discovered a newspaper report stating clinical success with plant extracts in Alzheimer's disease. The mode of action was said to be comparable to that of the synthetic compound 'carbamylcholin'; that is, carbachol. He bought 25 g of carbachol as pure substance in a pharmacy, and the father was administered 400 to 500 mg. Carbachol concentrations in serum and urine on day 1 and 2 of hospital admission were analysed by HPLC-mass spectrometry. RESULTS: Minutes after oral administration, the patient developed nausea, sweating and hypotension, and finally collapsed. Bradycardia, cholinergic symptoms and asystole occurred. Initial cardiopulmonary resuscitation and immediate treatment with adrenaline (epinephrine), atropine and furosemide was successful. On hospital admission, blood pressure of the intubated, bradyarrhythmic patient was 100\/65 mmHg. Further signs were hyperhidrosis, hypersalivation, bronchorrhoea, and severe miosis; the electrocardiographic finding was atrio-ventricular dissociation. High doses of atropine (up to 50 mg per 24 hours), adrenaline and dopamine were necessary. The patient was extubated 1 week later. However, increased dyspnoea and bronchospasm necessitated reintubation. Respiratory insufficiency was further worsened by Proteus mirabilis infection and severe bronchoconstriction. One week later, the patient was again extubated and 3 days later was transferred to a peripheral ward. On the next day he died, probably as a result of heart failure. Serum samples from the first and second days contained 3.6 and 1.9 mg\/l carbachol, respectively. The corresponding urine concentrations amounted to 374 and 554 mg\/l. CONCLUSION: This case started with a media report in a popular newspaper, initiated by published, peer-reviewed research on herbals, and involved human failure in a case history, medical examination and clinical treatment. For the first time, an analytical method for the determination of carbachol in plasma and urine has been developed. The analysed carbachol concentration exceeded the supposed serum level resulting from a therapeutic dose by a factor of 130 to 260. Especially in old patients, intensivists should consider intoxications (with cholinergics) as a cause of acute cardiovascular failure."],"offsets":[[57,2524]]}],"entities":[{"id":"23262","type":"Chemical","text":["carbachol"],"offsets":[[33,42]],"normalized":[{"db_name":"MESH","db_id":"D002217"}]},{"id":"23263","type":"Chemical","text":["carbachol"],"offsets":[[90,99]],"normalized":[{"db_name":"MESH","db_id":"D002217"}]},{"id":"23264","type":"Disease","text":["poisoning"],"offsets":[[212,221]],"normalized":[{"db_name":"MESH","db_id":"D011041"}]},{"id":"23265","type":"Disease","text":["Alzheimer's 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{"id":"23367","document_id":"12464714","passages":[{"id":"23368","type":"title","text":["Crossover comparison of efficacy and preference for rizatriptan 10 mg versus ergotamine\/caffeine in migraine."],"offsets":[[0,109]]},{"id":"23369","type":"abstract","text":["Rizatriptan is a selective 5-HT(1B\/1D) receptor agonist with rapid oral absorption and early onset of action in the acute treatment of migraine. This randomized double- blind crossover outpatient study assessed the preference for 1 rizatriptan 10 mg tablet to 2 ergotamine 1 mg\/caffeine 100 mg tablets in 439 patients treating a single migraine attack with each therapy. Of patients expressing a preference (89.1%), more than twice as many preferred rizatriptan to ergotamine\/caffeine (69.9 vs. 30.1%, p < or = 0.001). Faster relief of headache was the most important reason for preference, cited by 67.3% of patients preferring rizatriptan and 54.2% of patients who preferred ergotamine\/caffeine. The co-primary endpoint of being pain free at 2 h was also in favor of rizatriptan. Forty-nine percent of patients were pain free 2 h after rizatriptan, compared with 24.3% treated with ergotamine\/caffeine (p < or = 0.001), rizatriptan being superior within 1 h of treatment. Headache relief at 2 h was 75.9% for rizatriptan and 47.3% for ergotamine\/caffeine (p < or = 0.001), with rizatriptan being superior to ergotamine\/caffeine within 30 min of dosing. Almost 36% of patients taking rizatriptan were pain free at 2 h and had no recurrence or need for additional medication within 24 h, compared to 20% of patients on ergotamine\/caffeine (p < or = 0.001). Rizatriptan was also superior to ergotamine\/caffeine in the proportions of patients with no nausea, vomiting, phonophobia or photophobia and for patients with normal function 2 h after drug intake (p < or = 0.001). More patients were (completely, very or somewhat) satisfied 2 h after treatment with rizatriptan (69.8%) than at 2 h after treatment with ergotamine\/caffeine (38.6%, p < or = 0.001). Recurrence rates were 31.4% with rizatriptan and 15.3% with ergotamine\/caffeine. Both active treatments were well tolerated. The most common adverse events (incidence > or = 5% in one group) after rizatriptan and ergotamine\/caffeine, respectively, were dizziness (6.7 and 5.3%), nausea (4.2 and 8.5%) and somnolence (5.5 and 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{"id":"23470","document_id":"6203452","passages":[{"id":"23471","type":"title","text":["Thrombotic microangiopathy and renal failure associated with antineoplastic chemotherapy."],"offsets":[[0,89]]},{"id":"23472","type":"abstract","text":["Five patients with carcinoma developed thrombotic microangiopathy (characterized by renal insufficiency, microangiopathic hemolytic anemia, and usually thrombocytopenia) after treatment with cisplatin, bleomycin, and a vinca alkaloid. One patient had thrombotic thrombocytopenic purpura, three the hemolytic-uremic syndrome, and one an apparent forme fruste of one of these disorders. Histologic examination of the renal tissue showed evidence of intravascular coagulation, primarily affecting the small arteries, arterioles, and glomeruli. Because each patient was tumor-free or had only a small tumor at the onset of this syndrome, the thrombotic microangiopathy may have been induced by chemotherapy. Diagnosis of this potentially fatal complication may be delayed or missed if renal tissue or the peripheral blood smear is not examined, because renal failure may be ascribed to cisplatin nephrotoxicity and the anemia and thrombocytopenia to drug-induced bone marrow suppression."],"offsets":[[90,1073]]}],"entities":[{"id":"23473","type":"Disease","text":["Thrombotic microangiopathy"],"offsets":[[0,26]],"normalized":[{"db_name":"MESH","db_id":"D057049"}]},{"id":"23474","type":"Disease","text":["renal failure"],"offsets":[[31,44]],"normalized":[{"db_name":"MESH","db_id":"D051437"}]},{"id":"23475","type":"Disease","text":["carcinoma"],"offsets":[[109,118]],"normalized":[{"db_name":"MESH","db_id":"D002277"}]},{"id":"23476","type":"Disease","text":["thrombotic microangiopathy"],"offsets":[[129,155]],"normalized":[{"db_name":"MESH","db_id":"D057049"}]},{"id":"23477","type":"Disease","text":["renal insufficiency"],"offsets":[[174,193]],"normalized":[{"db_name":"MESH","db_id":"D051437"}]},{"id":"23478","type":"Disease","text":["microangiopathic hemolytic anemia"],"offsets":[[195,228]],"normalized":[{"db_name":"MESH","db_id":"D000743"}]},{"id":"23479","type":"Disease","text":["thrombocytopenia"],"offsets":[[242,258]],"normalized":[{"db_name":"MESH","db_id":"D013921"}]},{"id":"23480","type":"Chemical","text":["cisplatin"],"offsets":[[281,290]],"normalized":[{"db_name":"MESH","db_id":"D002945"}]},{"id":"23481","type":"Chemical","text":["bleomycin"],"offsets":[[292,301]],"normalized":[{"db_name":"MESH","db_id":"D001761"}]},{"id":"23482","type":"Chemical","text":["vinca alkaloid"],"offsets":[[309,323]],"normalized":[{"db_name":"MESH","db_id":"D014748"}]},{"id":"23483","type":"Disease","text":["thrombotic thrombocytopenic purpura"],"offsets":[[341,376]],"normalized":[{"db_name":"MESH","db_id":"D011697"}]},{"id":"23484","type":"Disease","text":["hemolytic-uremic syndrome"],"offsets":[[388,413]],"normalized":[{"db_name":"MESH","db_id":"D006463"}]},{"id":"23485","type":"Disease","text":["intravascular coagulation"],"offsets":[[537,562]],"normalized":[{"db_name":"MESH","db_id":"D004211"}]},{"id":"23486","type":"Disease","text":["tumor"],"offsets":[[656,661]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"23487","type":"Disease","text":["tumor"],"offsets":[[687,692]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"23488","type":"Disease","text":["thrombotic microangiopathy"],"offsets":[[728,754]],"normalized":[{"db_name":"MESH","db_id":"D057049"}]},{"id":"23489","type":"Disease","text":["renal failure"],"offsets":[[939,952]],"normalized":[{"db_name":"MESH","db_id":"D051437"}]},{"id":"23490","type":"Chemical","text":["cisplatin"],"offsets":[[972,981]],"normalized":[{"db_name":"MESH","db_id":"D002945"}]},{"id":"23491","type":"Disease","text":["nephrotoxicity"],"offsets":[[982,996]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"23492","type":"Disease","text":["anemia"],"offsets":[[1005,1011]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]},{"id":"23493","type":"Disease","text":["thrombocytopenia"],"offsets":[[1016,1032]],"normalized":[{"db_name":"MESH","db_id":"D013921"}]},{"id":"23494","type":"Disease","text":["bone marrow suppression"],"offsets":[[1049,1072]],"normalized":[{"db_name":"MESH","db_id":"D001855"}]}],"events":[],"coreferences":[],"relations":[{"id":"23495","type":"CID","arg1_id":"23481","arg2_id":"23483","normalized":[]},{"id":"23496","type":"CID","arg1_id":"23482","arg2_id":"23484","normalized":[]},{"id":"23497","type":"CID","arg1_id":"23480","arg2_id":"23491","normalized":[]},{"id":"23498","type":"CID","arg1_id":"23490","arg2_id":"23491","normalized":[]},{"id":"23499","type":"CID","arg1_id":"23482","arg2_id":"23491","normalized":[]},{"id":"23500","type":"CID","arg1_id":"23480","arg2_id":"23483","normalized":[]},{"id":"23501","type":"CID","arg1_id":"23490","arg2_id":"23483","normalized":[]},{"id":"23502","type":"CID","arg1_id":"23481","arg2_id":"23484","normalized":[]},{"id":"23503","type":"CID","arg1_id":"23482","arg2_id":"23483","normalized":[]},{"id":"23504","type":"CID","arg1_id":"23480","arg2_id":"23484","normalized":[]},{"id":"23505","type":"CID","arg1_id":"23490","arg2_id":"23484","normalized":[]},{"id":"23506","type":"CID","arg1_id":"23481","arg2_id":"23491","normalized":[]}]}
{"id":"23507","document_id":"20528871","passages":[{"id":"23508","type":"title","text":["Salvage therapy with nelarabine, etoposide, and cyclophosphamide in relapsed\/refractory paediatric T-cell lymphoblastic leukaemia and lymphoma."],"offsets":[[0,143]]},{"id":"23509","type":"abstract","text":["A combination of 5 d of nelarabine (AraG) with 5 d of etoposide (VP) and cyclophosphamide (CPM) and prophylactic intrathecal chemotherapy was used as salvage therapy in seven children with refractory or relapsed T-cell leukaemia or lymphoma. The most common side effects attributable to the AraG included Grade 2 and 3 sensory and motor neuropathy and musculoskeletal pain. Haematological toxicity was greater for the combination than AraG alone, although median time to neutrophil and platelet recovery was consistent with other salvage therapies. All patients had some response to the combined therapy and five of the seven went into complete remission after one or two courses of AraG\/VP\/CPM. Our experience supports the safety of giving AraG as salvage therapy in synchrony with etoposide and cyclophosphamide, although neurological toxicity must be closely monitored."],"offsets":[[144,1016]]}],"entities":[{"id":"23510","type":"Chemical","text":["nelarabine"],"offsets":[[21,31]],"normalized":[{"db_name":"MESH","db_id":"C104457"}]},{"id":"23511","type":"Chemical","text":["etoposide"],"offsets":[[33,42]],"normalized":[{"db_name":"MESH","db_id":"D005047"}]},{"id":"23512","type":"Chemical","text":["cyclophosphamide"],"offsets":[[48,64]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"23513","type":"Disease","text":["T-cell lymphoblastic leukaemia and lymphoma"],"offsets":[[99,142]],"normalized":[{"db_name":"MESH","db_id":"D015458"},{"db_name":"MESH","db_id":"D016399"}]},{"id":"23514","type":"Disease","text":["T-cell lymphoblastic leukaemia"],"offsets":[[99,129]],"normalized":[{"db_name":"MESH","db_id":"D015458"}]},{"id":"23515","type":"Disease","text":["T-cell 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{"id":"23565","document_id":"11672959","passages":[{"id":"23566","type":"title","text":["The 3-week sulphasalazine syndrome strikes again."],"offsets":[[0,49]]},{"id":"23567","type":"abstract","text":["A 34-year-old lady developed a constellation of dermatitis, fever, lymphadenopathy and hepatitis, beginning on the 17th day of a course of oral sulphasalazine for sero-negative rheumatoid arthritis. Cervical and inguinal lymph node biopsies showed the features of severe necrotising lymphadenitis, associated with erythrophagocytosis and prominent eosinophilic infiltrates, without viral inclusion bodies, suggestive of an adverse drug reaction.A week later, fulminant drug-induced hepatitis, associated with the presence of anti-nuclear autoantibodies (but not with other markers of autoimmunity), and accompanied by multi-organ failure and sepsis, supervened. She subsequently died some 5 weeks after the commencement of her drug therapy.Post-mortem examination showed evidence of massive hepatocellular necrosis, acute hypersensitivity myocarditis, focal acute tubulo-interstitial nephritis and extensive bone marrow necrosis, with no evidence of malignancy. It is thought that the clinico-pathological features and chronology of this case bore the hallmarks of the so-called \"3-week sulphasalazine syndrome\", a rare, but often fatal, immunoallergic reaction to sulphasalazine."],"offsets":[[50,1230]]}],"entities":[{"id":"23568","type":"Chemical","text":["sulphasalazine"],"offsets":[[11,25]],"normalized":[{"db_name":"MESH","db_id":"D012460"}]},{"id":"23569","type":"Disease","text":["dermatitis"],"offsets":[[98,108]],"normalized":[{"db_name":"MESH","db_id":"D003872"}]},{"id":"23570","type":"Disease","text":["fever"],"offsets":[[110,115]],"normalized":[{"db_name":"MESH","db_id":"D005334"}]},{"id":"23571","type":"Disease","text":["lymphadenopathy"],"offsets":[[117,132]],"normalized":[{"db_name":"MESH","db_id":"D008206"}]},{"id":"23572","type":"Disease","text":["hepatitis"],"offsets":[[137,146]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"23573","type":"Chemical","text":["sulphasalazine"],"offsets":[[194,208]],"normalized":[{"db_name":"MESH","db_id":"D012460"}]},{"id":"23574","type":"Disease","text":["rheumatoid arthritis"],"offsets":[[227,247]],"normalized":[{"db_name":"MESH","db_id":"D001172"}]},{"id":"23575","type":"Disease","text":["lymphadenitis"],"offsets":[[333,346]],"normalized":[{"db_name":"MESH","db_id":"D008199"}]},{"id":"23576","type":"Disease","text":["adverse drug reaction"],"offsets":[[473,494]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"23577","type":"Disease","text":["drug-induced hepatitis"],"offsets":[[519,541]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"23578","type":"Disease","text":["autoimmunity"],"offsets":[[634,646]],"normalized":[{"db_name":"MESH","db_id":"D001327"}]},{"id":"23579","type":"Disease","text":["multi-organ failure"],"offsets":[[668,687]],"normalized":[{"db_name":"MESH","db_id":"D009102"}]},{"id":"23580","type":"Disease","text":["sepsis"],"offsets":[[692,698]],"normalized":[{"db_name":"MESH","db_id":"D018805"}]},{"id":"23581","type":"Disease","text":["massive hepatocellular necrosis"],"offsets":[[833,864]],"normalized":[{"db_name":"MESH","db_id":"D047508"}]},{"id":"23582","type":"Disease","text":["myocarditis"],"offsets":[[889,900]],"normalized":[{"db_name":"MESH","db_id":"D009205"}]},{"id":"23583","type":"Disease","text":["nephritis"],"offsets":[[934,943]],"normalized":[{"db_name":"MESH","db_id":"D009393"}]},{"id":"23584","type":"Disease","text":["bone marrow necrosis"],"offsets":[[958,978]],"normalized":[{"db_name":"MESH","db_id":"D001855"}]},{"id":"23585","type":"Disease","text":["malignancy"],"offsets":[[1000,1010]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"23586","type":"Chemical","text":["sulphasalazine"],"offsets":[[1137,1151]],"normalized":[{"db_name":"MESH","db_id":"D012460"}]},{"id":"23587","type":"Chemical","text":["sulphasalazine"],"offsets":[[1215,1229]],"normalized":[{"db_name":"MESH","db_id":"D012460"}]}],"events":[],"coreferences":[],"relations":[{"id":"23588","type":"CID","arg1_id":"23568","arg2_id":"23570","normalized":[]},{"id":"23589","type":"CID","arg1_id":"23573","arg2_id":"23570","normalized":[]},{"id":"23590","type":"CID","arg1_id":"23586","arg2_id":"23570","normalized":[]},{"id":"23591","type":"CID","arg1_id":"23587","arg2_id":"23570","normalized":[]},{"id":"23592","type":"CID","arg1_id":"23568","arg2_id":"23582","normalized":[]},{"id":"23593","type":"CID","arg1_id":"23573","arg2_id":"23582","normalized":[]},{"id":"23594","type":"CID","arg1_id":"23586","arg2_id":"23582","normalized":[]},{"id":"23595","type":"CID","arg1_id":"23587","arg2_id":"23582","normalized":[]},{"id":"23596","type":"CID","arg1_id":"23568","arg2_id":"23571","normalized":[]},{"id":"23597","type":"CID","arg1_id":"23573","arg2_id":"23571","normalized":[]},{"id":"23598","type":"CID","arg1_id":"23586","arg2_id":"23571","normalized":[]},{"id":"23599","type":"CID","arg1_id":"23587","arg2_id":"23571","normalized":[]},{"id":"23600","type":"CID","arg1_id":"23568","arg2_id":"23580","normalized":[]},{"id":"23601","type":"CID","arg1_id":"23573","arg2_id":"23580","normalized":[]},{"id":"23602","type":"CID","arg1_id":"23586","arg2_id":"23580","normalized":[]},{"id":"23603","type":"CID","arg1_id":"23587","arg2_id":"23580","normalized":[]},{"id":"23604","type":"CID","arg1_id":"23568","arg2_id":"23583","normalized":[]},{"id":"23605","type":"CID","arg1_id":"23573","arg2_id":"23583","normalized":[]},{"id":"23606","type":"CID","arg1_id":"23586","arg2_id":"23583","normalized":[]},{"id":"23607","type":"CID","arg1_id":"23587","arg2_id":"23583","normalized":[]},{"id":"23608","type":"CID","arg1_id":"23568","arg2_id":"23569","normalized":[]},{"id":"23609","type":"CID","arg1_id":"23573","arg2_id":"23569","normalized":[]},{"id":"23610","type":"CID","arg1_id":"23586","arg2_id":"23569","normalized":[]},{"id":"23611","type":"CID","arg1_id":"23587","arg2_id":"23569","normalized":[]},{"id":"23612","type":"CID","arg1_id":"23568","arg2_id":"23572","normalized":[]},{"id":"23613","type":"CID","arg1_id":"23568","arg2_id":"23577","normalized":[]},{"id":"23614","type":"CID","arg1_id":"23573","arg2_id":"23572","normalized":[]},{"id":"23615","type":"CID","arg1_id":"23573","arg2_id":"23577","normalized":[]},{"id":"23616","type":"CID","arg1_id":"23586","arg2_id":"23572","normalized":[]},{"id":"23617","type":"CID","arg1_id":"23586","arg2_id":"23577","normalized":[]},{"id":"23618","type":"CID","arg1_id":"23587","arg2_id":"23572","normalized":[]},{"id":"23619","type":"CID","arg1_id":"23587","arg2_id":"23577","normalized":[]}]}
{"id":"23620","document_id":"11928786","passages":[{"id":"23621","type":"title","text":["Bupropion (Zyban) toxicity."],"offsets":[[0,27]]},{"id":"23622","type":"abstract","text":["Bupropion is a monocyclic antidepressant structurally related to amphetamine. Zyban, a sustained-release formulation of bupropion hydrochloride, was recently released in Ireland, as a smoking cessation aid. In the initial 6 months since it's introduction, 12 overdose cases have been reported to The National Poisons Information Centre. 8 patients developed symptoms of toxicity. Common features included tachycardia, drowsiness, hallucinations and convulsions. Two patients developed severe cardiac arrhythmias, including one patient who was resuscitated following a cardiac arrest. All patients recovered without sequelae. We report a case of a 31 year old female who required admission to the Intensive Care Unit for ventilation and full supportive therapy, following ingestion of 13.5g bupropion. Recurrent seizures were treated with diazepam and broad complex tachycardia was successfully treated with adenosine. Zyban caused significant neurological and cardiovascular toxicity in overdose. The potential toxic effects should be considered when prescribing it as a smoking cessation aid."],"offsets":[[28,1121]]}],"entities":[{"id":"23623","type":"Chemical","text":["Bupropion"],"offsets":[[0,9]],"normalized":[{"db_name":"MESH","db_id":"D016642"}]},{"id":"23624","type":"Chemical","text":["Zyban"],"offsets":[[11,16]],"normalized":[{"db_name":"MESH","db_id":"D016642"}]},{"id":"23625","type":"Disease","text":["toxicity"],"offsets":[[18,26]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"23626","type":"Chemical","text":["Bupropion"],"offsets":[[28,37]],"normalized":[{"db_name":"MESH","db_id":"D016642"}]},{"id":"23627","type":"Chemical","text":["antidepressant"],"offsets":[[54,68]],"normalized":[{"db_name":"MESH","db_id":"D000928"}]},{"id":"23628","type":"Chemical","text":["amphetamine"],"offsets":[[93,104]],"normalized":[{"db_name":"MESH","db_id":"D000661"}]},{"id":"23629","type":"Chemical","text":["Zyban"],"offsets":[[106,111]],"normalized":[{"db_name":"MESH","db_id":"D016642"}]},{"id":"23630","type":"Chemical","text":["bupropion hydrochloride"],"offsets":[[148,171]],"normalized":[{"db_name":"MESH","db_id":"D016642"}]},{"id":"23631","type":"Disease","text":["overdose"],"offsets":[[287,295]],"normalized":[{"db_name":"MESH","db_id":"D062787"}]},{"id":"23632","type":"Disease","text":["toxicity"],"offsets":[[398,406]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"23633","type":"Disease","text":["tachycardia"],"offsets":[[433,444]],"normalized":[{"db_name":"MESH","db_id":"D013610"}]},{"id":"23634","type":"Disease","text":["hallucinations"],"offsets":[[458,472]],"normalized":[{"db_name":"MESH","db_id":"D006212"}]},{"id":"23635","type":"Disease","text":["convulsions"],"offsets":[[477,488]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"23636","type":"Disease","text":["cardiac arrhythmias"],"offsets":[[520,539]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"23637","type":"Disease","text":["cardiac arrest"],"offsets":[[596,610]],"normalized":[{"db_name":"MESH","db_id":"D006323"}]},{"id":"23638","type":"Chemical","text":["bupropion"],"offsets":[[818,827]],"normalized":[{"db_name":"MESH","db_id":"D016642"}]},{"id":"23639","type":"Disease","text":["seizures"],"offsets":[[839,847]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"23640","type":"Chemical","text":["diazepam"],"offsets":[[866,874]],"normalized":[{"db_name":"MESH","db_id":"D003975"}]},{"id":"23641","type":"Disease","text":["tachycardia"],"offsets":[[893,904]],"normalized":[{"db_name":"MESH","db_id":"D013610"}]},{"id":"23642","type":"Chemical","text":["adenosine"],"offsets":[[935,944]],"normalized":[{"db_name":"MESH","db_id":"D000241"}]},{"id":"23643","type":"Chemical","text":["Zyban"],"offsets":[[946,951]],"normalized":[{"db_name":"MESH","db_id":"D016642"}]},{"id":"23644","type":"Disease","text":["neurological and cardiovascular toxicity"],"offsets":[[971,1011]],"normalized":[{"db_name":"MESH","db_id":"D020258"},{"db_name":"MESH","db_id":"D002318"}]},{"id":"23645","type":"Disease","text":["neurological","toxicity"],"offsets":[[971,983],[1003,1011]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"23646","type":"Disease","text":["cardiovascular toxicity"],"offsets":[[988,1011]],"normalized":[{"db_name":"MESH","db_id":"D002318"}]},{"id":"23647","type":"Disease","text":["overdose"],"offsets":[[1015,1023]],"normalized":[{"db_name":"MESH","db_id":"D062787"}]}],"events":[],"coreferences":[],"relations":[{"id":"23648","type":"CID","arg1_id":"23623","arg2_id":"23633","normalized":[]},{"id":"23649","type":"CID","arg1_id":"23623","arg2_id":"23641","normalized":[]},{"id":"23650","type":"CID","arg1_id":"23624","arg2_id":"23633","normalized":[]},{"id":"23651","type":"CID","arg1_id":"23624","arg2_id":"23641","normalized":[]},{"id":"23652","type":"CID","arg1_id":"23626","arg2_id":"23633","normalized":[]},{"id":"23653","type":"CID","arg1_id":"23626","arg2_id":"23641","normalized":[]},{"id":"23654","type":"CID","arg1_id":"23629","arg2_id":"23633","normalized":[]},{"id":"23655","type":"CID","arg1_id":"23629","arg2_id":"23641","normalized":[]},{"id":"23656","type":"CID","arg1_id":"23630","arg2_id":"23633","normalized":[]},{"id":"23657","type":"CID","arg1_id":"23630","arg2_id":"23641","normalized":[]},{"id":"23658","type":"CID","arg1_id":"23638","arg2_id":"23633","normalized":[]},{"id":"23659","type":"CID","arg1_id":"23638","arg2_id":"23641","normalized":[]},{"id":"23660","type":"CID","arg1_id":"23643","arg2_id":"23633","normalized":[]},{"id":"23661","type":"CID","arg1_id":"23643","arg2_id":"23641","normalized":[]},{"id":"23662","type":"CID","arg1_id":"23623","arg2_id":"23635","normalized":[]},{"id":"23663","type":"CID","arg1_id":"23623","arg2_id":"23639","normalized":[]},{"id":"23664","type":"CID","arg1_id":"23624","arg2_id":"23635","normalized":[]},{"id":"23665","type":"CID","arg1_id":"23624","arg2_id":"23639","normalized":[]},{"id":"23666","type":"CID","arg1_id":"23626","arg2_id":"23635","normalized":[]},{"id":"23667","type":"CID","arg1_id":"23626","arg2_id":"23639","normalized":[]},{"id":"23668","type":"CID","arg1_id":"23629","arg2_id":"23635","normalized":[]},{"id":"23669","type":"CID","arg1_id":"23629","arg2_id":"23639","normalized":[]},{"id":"23670","type":"CID","arg1_id":"23630","arg2_id":"23635","normalized":[]},{"id":"23671","type":"CID","arg1_id":"23630","arg2_id":"23639","normalized":[]},{"id":"23672","type":"CID","arg1_id":"23638","arg2_id":"23635","normalized":[]},{"id":"23673","type":"CID","arg1_id":"23638","arg2_id":"23639","normalized":[]},{"id":"23674","type":"CID","arg1_id":"23643","arg2_id":"23635","normalized":[]},{"id":"23675","type":"CID","arg1_id":"23643","arg2_id":"23639","normalized":[]},{"id":"23676","type":"CID","arg1_id":"23623","arg2_id":"23634","normalized":[]},{"id":"23677","type":"CID","arg1_id":"23624","arg2_id":"23634","normalized":[]},{"id":"23678","type":"CID","arg1_id":"23626","arg2_id":"23634","normalized":[]},{"id":"23679","type":"CID","arg1_id":"23629","arg2_id":"23634","normalized":[]},{"id":"23680","type":"CID","arg1_id":"23630","arg2_id":"23634","normalized":[]},{"id":"23681","type":"CID","arg1_id":"23638","arg2_id":"23634","normalized":[]},{"id":"23682","type":"CID","arg1_id":"23643","arg2_id":"23634","normalized":[]},{"id":"23683","type":"CID","arg1_id":"23623","arg2_id":"23636","normalized":[]},{"id":"23684","type":"CID","arg1_id":"23624","arg2_id":"23636","normalized":[]},{"id":"23685","type":"CID","arg1_id":"23626","arg2_id":"23636","normalized":[]},{"id":"23686","type":"CID","arg1_id":"23629","arg2_id":"23636","normalized":[]},{"id":"23687","type":"CID","arg1_id":"23630","arg2_id":"23636","normalized":[]},{"id":"23688","type":"CID","arg1_id":"23638","arg2_id":"23636","normalized":[]},{"id":"23689","type":"CID","arg1_id":"23643","arg2_id":"23636","normalized":[]},{"id":"23690","type":"CID","arg1_id":"23623","arg2_id":"23637","normalized":[]},{"id":"23691","type":"CID","arg1_id":"23624","arg2_id":"23637","normalized":[]},{"id":"23692","type":"CID","arg1_id":"23626","arg2_id":"23637","normalized":[]},{"id":"23693","type":"CID","arg1_id":"23629","arg2_id":"23637","normalized":[]},{"id":"23694","type":"CID","arg1_id":"23630","arg2_id":"23637","normalized":[]},{"id":"23695","type":"CID","arg1_id":"23638","arg2_id":"23637","normalized":[]},{"id":"23696","type":"CID","arg1_id":"23643","arg2_id":"23637","normalized":[]}]}
{"id":"23697","document_id":"7977601","passages":[{"id":"23698","type":"title","text":["Survey of complications of indocyanine green angiography in Japan."],"offsets":[[0,66]]},{"id":"23699","type":"abstract","text":["PURPOSE: We evaluated the safety of indocyanine green for use in fundus angiography. METHODS: We sent a questionnaire concerning complications of indocyanine green to 32 institutions in Japan, which were selected on the basis of the client list from the Topcon Company, which manufactures the indocyanine green fundus camera. RESULTS: Ophthalmologists at 15 institutions responded, reporting a total of 3,774 indocyanine green angiograms performed on 2,820 patients between June 1984 and September 1992. Before angiography, intradermal or intravenous indocyanine green testing, or both was performed at 13 of 15 institutions. For three patients, the decision was made not to proceed with angiography after positive preangiographic testing. The dosage of indocyanine green used for angiography varied from 25 to 75 mg, depending upon the institution. There were 13 cases of adverse reactions (0.34%), ten of which were mild reactions such as nausea, exanthema, urtication, itchiness, and urgency to defecate, and did not require treatment. Also recorded were one case of pain of the vein, which required treatment, and two cases of hypotension. The two hypotensive patients required treatment for shock. CONCLUSIONS: A comparison of frequency of adverse reactions to indocyanine green with the previously reported frequency of such reactions to fluorescein sodium indicated that indocyanine green is a safe as fluorescein for use in angiography."],"offsets":[[67,1511]]}],"entities":[{"id":"23700","type":"Chemical","text":["indocyanine green"],"offsets":[[27,44]],"normalized":[{"db_name":"MESH","db_id":"D007208"}]},{"id":"23701","type":"Chemical","text":["indocyanine green"],"offsets":[[103,120]],"normalized":[{"db_name":"MESH","db_id":"D007208"}]},{"id":"23702","type":"Chemical","text":["indocyanine green"],"offsets":[[213,230]],"normalized":[{"db_name":"MESH","db_id":"D007208"}]},{"id":"23703","type":"Chemical","text":["indocyanine green"],"offsets":[[360,377]],"normalized":[{"db_name":"MESH","db_id":"D007208"}]},{"id":"23704","type":"Chemical","text":["indocyanine 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":"CID","arg1_id":"23705","arg2_id":"23708","normalized":[]},{"id":"23779","type":"CID","arg1_id":"23706","arg2_id":"23708","normalized":[]},{"id":"23780","type":"CID","arg1_id":"23715","arg2_id":"23708","normalized":[]},{"id":"23781","type":"CID","arg1_id":"23717","arg2_id":"23708","normalized":[]},{"id":"23782","type":"CID","arg1_id":"23700","arg2_id":"23709","normalized":[]},{"id":"23783","type":"CID","arg1_id":"23701","arg2_id":"23709","normalized":[]},{"id":"23784","type":"CID","arg1_id":"23702","arg2_id":"23709","normalized":[]},{"id":"23785","type":"CID","arg1_id":"23703","arg2_id":"23709","normalized":[]},{"id":"23786","type":"CID","arg1_id":"23704","arg2_id":"23709","normalized":[]},{"id":"23787","type":"CID","arg1_id":"23705","arg2_id":"23709","normalized":[]},{"id":"23788","type":"CID","arg1_id":"23706","arg2_id":"23709","normalized":[]},{"id":"23789","type":"CID","arg1_id":"23715","arg2_id":"23709","normalized":[]},{"id":"23790","type":"CID","arg1_id":"23717","arg2_id":"23709","normalized":[]}]}
{"id":"23791","document_id":"19300402","passages":[{"id":"23792","type":"title","text":["Bradykinin receptors antagonists and nitric oxide synthase inhibitors in vincristine and streptozotocin induced hyperalgesia in chemotherapy and diabetic neuropathy rat model."],"offsets":[[0,175]]},{"id":"23793","type":"abstract","text":["PURPOSE: The influence of an irreversible inhibitor of constitutive NO synthase (L-NOArg; 1.0 mg\/kg ip), a relatively selective inhibitor of inducible NO synthase (L-NIL; 1.0 mg\/kg ip) and a relatively specific inhibitor of neuronal NO synthase (7-NI; 0.1 mg\/kg ip), on antihyperalgesic action of selective antagonists of B2 and B1 receptors: D-Arg-[Hyp3,Thi5,D-Tic7,Oic8] bradykinin (HOE 140; 70 nmol\/kg ip) or des Arg10 HOE 140 (70 nmol\/kg ip) respectively, in model of diabetic (streptozotocin-induced) and toxic (vincristine-induced) neuropathy was investigated. METHODS: The changes in pain thresholds were determined using mechanical stimuli--the modification of the classic paw withdrawal test described by Randall-Selitto. RESULTS: The results of this paper confirm that inhibition of bradykinin receptors and inducible NO synthase but not neuronal NO synthase activity reduces diabetic hyperalgesia. Pretreatment with L-NOArg and L-NIL but not 7-NI, significantly increases antihyperalgesic activity both HOE 140 and des Arg10 HOE 140. It was also shown that both products of inducible NO synthase and neuronal NO synthase activation as well as bradykinin are involved in hyperalgesia produced by vincristine. Moreover, L-NOArg and 7-NI but not L-NIL intensify antihyperalgesic activity of HOE 140 or des-Arg10HOE 140 in toxic neuropathy. CONCLUSIONS: Results of these studies suggest that B1 and B2 receptors are engaged in transmission of nociceptive stimuli in both diabetic and toxic neuropathy. In streptozotocin-induced hyperalgesia, inducible NO synthase participates in pronociceptive activity of bradykinin, whereas in vincristine-induced hyperalgesia bradykinin seemed to activate neuronal NO synthase pathway. Therefore, concomitant administration of small doses of bradykinin receptor antagonists and NO synthase inhibitors can be effective in alleviation of neuropathic pain, even in hospital care."],"offsets":[[176,2096]]}],"entities":[{"id":"23794","type":"Chemical","text":["Bradykinin"],"offsets":[[0,10]],"normalized":[{"db_name":"MESH","db_id":"D001920"}]},{"id":"23795","type":"Chemical","text":["nitric oxide"],"offsets":[[37,49]],"normalized":[{"db_name":"MESH","db_id":"D009569"}]},{"id":"23796","type":"Chemical","text":["vincristine"],"offsets":[[73,84]],"normalized":[{"db_name":"MESH","db_id":"D014750"}]},{"id":"23797","type":"Chemical","text":["streptozotocin"],"offsets":[[89,103]],"normalized":[{"db_name":"MESH","db_id":"D013311"}]},{"id":"23798","type":"Disease","text":["hyperalgesia"],"offsets":[[112,124]],"normalized":[{"db_name":"MESH","db_id":"D006930"}]},{"id":"23799","type":"Disease","text":["diabetic 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neuropathy"],"offsets":[[648,724]],"normalized":[{"db_name":"MESH","db_id":"D003929"},{"db_name":"MESH","db_id":"D010523"}]},{"id":"23807","type":"Disease","text":["diabetic (streptozotocin-induced)","neuropathy"],"offsets":[[648,681],[714,724]],"normalized":[{"db_name":"MESH","db_id":"D003929"}]},{"id":"23808","type":"Disease","text":["toxic (vincristine-induced) neuropathy"],"offsets":[[686,724]],"normalized":[{"db_name":"MESH","db_id":"D010523"}]},{"id":"23809","type":"Disease","text":["pain"],"offsets":[[767,771]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"23810","type":"Chemical","text":["bradykinin"],"offsets":[[969,979]],"normalized":[{"db_name":"MESH","db_id":"D001920"}]},{"id":"23811","type":"Chemical","text":["NO"],"offsets":[[1004,1006]],"normalized":[{"db_name":"MESH","db_id":"D009569"}]},{"id":"23812","type":"Chemical","text":["NO"],"offsets":[[1033,1035]],"normalized":[{"db_name":"MESH","db_id":"D009569"}]},{"id":"23813","type":"Disease","text":["diabetic hyperalgesia"],"offsets":[[1062,1083]],"normalized":[{"db_name":"MESH","db_id":"D006930"}]},{"id":"23814","type":"Chemical","text":["HOE 140"],"offsets":[[1190,1197]],"normalized":[{"db_name":"MESH","db_id":"C065679"}]},{"id":"23815","type":"Chemical","text":["des Arg10 HOE 140"],"offsets":[[1202,1219]],"normalized":[{"db_name":"MESH","db_id":"C078665"}]},{"id":"23816","type":"Chemical","text":["NO"],"offsets":[[1271,1273]],"normalized":[{"db_name":"MESH","db_id":"D009569"}]},{"id":"23817","type":"Chemical","text":["NO"],"offsets":[[1296,1298]],"normalized":[{"db_name":"MESH","db_id":"D009569"}]},{"id":"23818","type":"Chemical","text":["bradykinin"],"offsets":[[1330,1340]],"normalized":[{"db_name":"MESH","db_id":"D001920"}]},{"id":"23819","type":"Disease","text":["hyperalgesia"],"offsets":[[1357,1369]],"normalized":[{"db_name":"MESH","db_id":"D006930"}]},{"id":"23820","type":"Chemical","text":["vincristine"],"offsets":[[1382,1393]],"normalized":[{"db_name":"MESH","db_id":"D014750"}]},{"id":"23821","type":"Chemical","text":["HOE 140"],"offsets":[[1475,1482]],"normalized":[{"db_name":"MESH","db_id":"C065679"}]},{"id":"23822","type":"Chemical","text":["des-Arg10HOE 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{"id":"23888","document_id":"15325671","passages":[{"id":"23889","type":"title","text":["Cardiac toxicity observed in association with high-dose cyclophosphamide-based chemotherapy for metastatic breast cancer."],"offsets":[[0,121]]},{"id":"23890","type":"abstract","text":["INTRODUCTION: Cyclophosphamide is an alkylating agent given frequently as a component of many conditioning regimens. In high doses, its nonhematological dose-limiting toxicity is cardiomyopathy. STUDY DESIGN: We combined paclitaxel, melphalan and high-dose cyclophosphamide, thiotepa, and carboplatin in a triple sequential high-dose regimen for patients with metastatic breast cancer. Analysis was performed on 61 women with chemotherapy-responsive metastatic breast cancer receiving 96-h infusional cyclophosphamide as part of a triple sequential high-dose regimen to assess association between presence of peritransplant congestive heart failure (CHF) and the following pretreatment characteristics: presence of electrocardiogram (EKG) abnormalities, age, hypertension, prior cardiac history, smoking, diabetes mellitus, prior use of anthracyclines, and left-sided chest irradiation. RESULTS: Six of 61 women (10%) developed clinically reversible grade 3 CHF following infusional cyclophosphamide with a median percent decline in ejection fraction of 31%. Incidence of transient cyclophosphamide-related cardiac toxicity (10%) is comparable to previous recorded literature. Older age was significantly correlated with the CHF development; with median ages for the entire group and for patients developing CHF of 45 and 59, respectively. No association was found with other pretreatment characteristics. CONCLUSIONS: As a result of these findings, oncologists should carefully monitor fluid balance in older patients. Routine EKG monitoring during infusional cyclophosphamide did not predict CHF development."],"offsets":[[122,1732]]}],"entities":[{"id":"23891","type":"Disease","text":["Cardiac toxicity"],"offsets":[[0,16]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"23892","type":"Chemical","text":["cyclophosphamide"],"offsets":[[56,72]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"23893","type":"Disease","text":["breast cancer"],"offsets":[[107,120]],"normalized":[{"db_name":"MESH","db_id":"D001943"}]},{"id":"23894","type":"Chemical","text":["Cyclophosphamide"],"offsets":[[136,152]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"23895","type":"Disease","text":["toxicity"],"offsets":[[289,297]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"23896","type":"Disease","text":["cardiomyopathy"],"offsets":[[301,315]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"23897","type":"Chemical","text":["paclitaxel"],"offsets":[[343,353]],"normalized":[{"db_name":"MESH","db_id":"D017239"}]},{"id":"23898","type":"Chemical","text":["melphalan"],"offsets":[[355,364]],"normalized":[{"db_name":"MESH","db_id":"D008558"}]},{"id":"23899","type":"Chemical","text":["cyclophosphamide"],"offsets":[[379,395]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"23900","type":"Chemical","text":["thiotepa"],"offsets":[[397,405]],"normalized":[{"db_name":"MESH","db_id":"D013852"}]},{"id":"23901","type":"Chemical","text":["carboplatin"],"offsets":[[411,422]],"normalized":[{"db_name":"MESH","db_id":"D016190"}]},{"id":"23902","type":"Disease","text":["breast cancer"],"offsets":[[493,506]],"normalized":[{"db_name":"MESH","db_id":"D001943"}]},{"id":"23903","type":"Disease","text":["breast cancer"],"offsets":[[583,596]],"normalized":[{"db_name":"MESH","db_id":"D001943"}]},{"id":"23904","type":"Chemical","text":["cyclophosphamide"],"offsets":[[623,639]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"23905","type":"Disease","text":["congestive heart failure"],"offsets":[[746,770]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]},{"id":"23906","type":"Disease","text":["CHF"],"offsets":[[772,775]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]},{"id":"23907","type":"Disease","text":["hypertension"],"offsets":[[881,893]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"23908","type":"Disease","text":["diabetes mellitus"],"offsets":[[927,944]],"normalized":[{"db_name":"MESH","db_id":"D003920"}]},{"id":"23909","type":"Chemical","text":["anthracyclines"],"offsets":[[959,973]],"normalized":[{"db_name":"MESH","db_id":"D018943"}]},{"id":"23910","type":"Disease","text":["CHF"],"offsets":[[1080,1083]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]},{"id":"23911","type":"Chemical","text":["cyclophosphamide"],"offsets":[[1105,1121]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"23912","type":"Chemical","text":["cyclophosphamide"],"offsets":[[1204,1220]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"23913","type":"Disease","text":["cardiac toxicity"],"offsets":[[1229,1245]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"23914","type":"Disease","text":["CHF"],"offsets":[[1347,1350]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]},{"id":"23915","type":"Disease","text":["CHF"],"offsets":[[1430,1433]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]},{"id":"23916","type":"Chemical","text":["cyclophosphamide"],"offsets":[[1683,1699]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"23917","type":"Disease","text":["CHF"],"offsets":[[1716,1719]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]}],"events":[],"coreferences":[],"relations":[{"id":"23918","type":"CID","arg1_id":"23892","arg2_id":"23905","normalized":[]},{"id":"23919","type":"CID","arg1_id":"23892","arg2_id":"23906","normalized":[]},{"id":"23920","type":"CID","arg1_id":"23892","arg2_id":"23910","normalized":[]},{"id":"23921","type":"CID","arg1_id":"23892","arg2_id":"23914","normalized":[]},{"id":"23922","type":"CID","arg1_id":"23892","arg2_id":"23915","normalized":[]},{"id":"23923","type":"CID","arg1_id":"23892","arg2_id":"23917","normalized":[]},{"id":"23924","type":"CID","arg1_id":"23894","arg2_id":"23905","normalized":[]},{"id":"23925","type":"CID","arg1_id":"23894","arg2_id":"23906","normalized":[]},{"id":"23926","type":"CID","arg1_id":"23894","arg2_id":"23910","normalized":[]},{"id":"23927","type":"CID","arg1_id":"23894","arg2_id":"23914","normalized":[]},{"id":"23928","type":"CID","arg1_id":"23894","arg2_id":"23915","normalized":[]},{"id":"23929","type":"CID","arg1_id":"23894","arg2_id":"23917","normalized":[]},{"id":"23930","type":"CID","arg1_id":"23899","arg2_id":"23905","normalized":[]},{"id":"23931","type":"CID","arg1_id":"23899","arg2_id":"23906","normalized":[]},{"id":"23932","type":"CID","arg1_id":"23899","arg2_id":"23910","normalized":[]},{"id":"23933","type":"CID","arg1_id":"23899","arg2_id":"23914","normalized":[]},{"id":"23934","type":"CID","arg1_id":"23899","arg2_id":"23915","normalized":[]},{"id":"23935","type":"CID","arg1_id":"23899","arg2_id":"23917","normalized":[]},{"id":"23936","type":"CID","arg1_id":"23904","arg2_id":"23905","normalized":[]},{"id":"23937","type":"CID","arg1_id":"23904","arg2_id":"23906","normalized":[]},{"id":"23938","type":"CID","arg1_id":"23904","arg2_id":"23910","normalized":[]},{"id":"23939","type":"CID","arg1_id":"23904","arg2_id":"23914","normalized":[]},{"id":"23940","type":"CID","arg1_id":"23904","arg2_id":"23915","normalized":[]},{"id":"23941","type":"CID","arg1_id":"23904","arg2_id":"23917","normalized":[]},{"id":"23942","type":"CID","arg1_id":"23911","arg2_id":"23905","normalized":[]},{"id":"23943","type":"CID","arg1_id":"23911","arg2_id":"23906","normalized":[]},{"id":"23944","type":"CID","arg1_id":"23911","arg2_id":"23910","normalized":[]},{"id":"23945","type":"CID","arg1_id":"23911","arg2_id":"23914","normalized":[]},{"id":"23946","type":"CID","arg1_id":"23911","arg2_id":"23915","normalized":[]},{"id":"23947","type":"CID","arg1_id":"23911","arg2_id":"23917","normalized":[]},{"id":"23948","type":"CID","arg1_id":"23912","arg2_id":"23905","normalized":[]},{"id":"23949","type":"CID","arg1_id":"23912","arg2_id":"23906","normalized":[]},{"id":"23950","type":"CID","arg1_id":"23912","arg2_id":"23910","normalized":[]},{"id":"23951","type":"CID","arg1_id":"23912","arg2_id":"23914","normalized":[]},{"id":"23952","type":"CID","arg1_id":"23912","arg2_id":"23915","normalized":[]},{"id":"23953","type":"CID","arg1_id":"23912","arg2_id":"23917","normalized":[]},{"id":"23954","type":"CID","arg1_id":"23916","arg2_id":"23905","normalized":[]},{"id":"23955","type":"CID","arg1_id":"23916","arg2_id":"23906","normalized":[]},{"id":"23956","type":"CID","arg1_id":"23916","arg2_id":"23910","normalized":[]},{"id":"23957","type":"CID","arg1_id":"23916","arg2_id":"23914","normalized":[]},{"id":"23958","type":"CID","arg1_id":"23916","arg2_id":"23915","normalized":[]},{"id":"23959","type":"CID","arg1_id":"23916","arg2_id":"23917","normalized":[]}]}
{"id":"23960","document_id":"9746003","passages":[{"id":"23961","type":"title","text":["Inappropriate use of carbamazepine and vigabatrin in typical absence seizures."],"offsets":[[0,78]]},{"id":"23962","type":"abstract","text":["Carbamazepine and vigabatrin are contraindicated in typical absence seizures. Of 18 consecutive referrals of children with resistant typical absences only, eight were erroneously treated with carbamazepine either as monotherapy or as an add-on. Vigabatrin was also used in the treatment of two children. Frequency of absences increased in four children treated with carbamazepine and two of these developed myoclonic jerks, which resolved on withdrawal of carbamazepine. Absences were aggravated in both cases where vigabatrin was added on to concurrent treatment. Optimal control of the absences was achieved with sodium valproate, lamotrigine, or ethosuximide alone or in combination."],"offsets":[[79,765]]}],"entities":[{"id":"23963","type":"Chemical","text":["carbamazepine"],"offsets":[[21,34]],"normalized":[{"db_name":"MESH","db_id":"D002220"}]},{"id":"23964","type":"Chemical","text":["vigabatrin"],"offsets":[[39,49]],"normalized":[{"db_name":"MESH","db_id":"D020888"}]},{"id":"23965","type":"Disease","text":["absence seizures"],"offsets":[[61,77]],"normalized":[{"db_name":"MESH","db_id":"D004832"}]},{"id":"23966","type":"Chemical","text":["Carbamazepine"],"offsets":[[79,92]],"normalized":[{"db_name":"MESH","db_id":"D002220"}]},{"id":"23967","type":"Chemical","text":["vigabatrin"],"offsets":[[97,107]],"normalized":[{"db_name":"MESH","db_id":"D020888"}]},{"id":"23968","type":"Disease","text":["absence seizures"],"offsets":[[139,155]],"normalized":[{"db_name":"MESH","db_id":"D004832"}]},{"id":"23969","type":"Chemical","text":["carbamazepine"],"offsets":[[271,284]],"normalized":[{"db_name":"MESH","db_id":"D002220"}]},{"id":"23970","type":"Chemical","text":["Vigabatrin"],"offsets":[[324,334]],"normalized":[{"db_name":"MESH","db_id":"D020888"}]},{"id":"23971","type":"Chemical","text":["carbamazepine"],"offsets":[[445,458]],"normalized":[{"db_name":"MESH","db_id":"D002220"}]},{"id":"23972","type":"Disease","text":["myoclonic jerks"],"offsets":[[486,501]],"normalized":[{"db_name":"MESH","db_id":"D009207"}]},{"id":"23973","type":"Chemical","text":["carbamazepine"],"offsets":[[535,548]],"normalized":[{"db_name":"MESH","db_id":"D002220"}]},{"id":"23974","type":"Chemical","text":["vigabatrin"],"offsets":[[595,605]],"normalized":[{"db_name":"MESH","db_id":"D020888"}]},{"id":"23975","type":"Chemical","text":["sodium valproate"],"offsets":[[694,710]],"normalized":[{"db_name":"MESH","db_id":"D014635"}]},{"id":"23976","type":"Chemical","text":["lamotrigine"],"offsets":[[712,723]],"normalized":[{"db_name":"MESH","db_id":"C047781"}]},{"id":"23977","type":"Chemical","text":["ethosuximide"],"offsets":[[728,740]],"normalized":[{"db_name":"MESH","db_id":"D005013"}]}],"events":[],"coreferences":[],"relations":[{"id":"23978","type":"CID","arg1_id":"23963","arg2_id":"23965","normalized":[]},{"id":"23979","type":"CID","arg1_id":"23963","arg2_id":"23968","normalized":[]},{"id":"23980","type":"CID","arg1_id":"23966","arg2_id":"23965","normalized":[]},{"id":"23981","type":"CID","arg1_id":"23966","arg2_id":"23968","normalized":[]},{"id":"23982","type":"CID","arg1_id":"23969","arg2_id":"23965","normalized":[]},{"id":"23983","type":"CID","arg1_id":"23969","arg2_id":"23968","normalized":[]},{"id":"23984","type":"CID","arg1_id":"23971","arg2_id":"23965","normalized":[]},{"id":"23985","type":"CID","arg1_id":"23971","arg2_id":"23968","normalized":[]},{"id":"23986","type":"CID","arg1_id":"23973","arg2_id":"23965","normalized":[]},{"id":"23987","type":"CID","arg1_id":"23973","arg2_id":"23968","normalized":[]},{"id":"23988","type":"CID","arg1_id":"23963","arg2_id":"23972","normalized":[]},{"id":"23989","type":"CID","arg1_id":"23966","arg2_id":"23972","normalized":[]},{"id":"23990","type":"CID","arg1_id":"23969","arg2_id":"23972","normalized":[]},{"id":"23991","type":"CID","arg1_id":"23971","arg2_id":"23972","normalized":[]},{"id":"23992","type":"CID","arg1_id":"23973","arg2_id":"23972","normalized":[]},{"id":"23993","type":"CID","arg1_id":"23964","arg2_id":"23965","normalized":[]},{"id":"23994","type":"CID","arg1_id":"23964","arg2_id":"23968","normalized":[]},{"id":"23995","type":"CID","arg1_id":"23967","arg2_id":"23965","normalized":[]},{"id":"23996","type":"CID","arg1_id":"23967","arg2_id":"23968","normalized":[]},{"id":"23997","type":"CID","arg1_id":"23970","arg2_id":"23965","normalized":[]},{"id":"23998","type":"CID","arg1_id":"23970","arg2_id":"23968","normalized":[]},{"id":"23999","type":"CID","arg1_id":"23974","arg2_id":"23965","normalized":[]},{"id":"24000","type":"CID","arg1_id":"23974","arg2_id":"23968","normalized":[]}]}
{"id":"24001","document_id":"1992636","passages":[{"id":"24002","type":"title","text":["Hemolytic anemia associated with the use of omeprazole."],"offsets":[[0,55]]},{"id":"24003","type":"abstract","text":["Omeprazole is the first drug designed to block the final step in the acid secretory process within the parietal cell. It has been shown to be extremely effective in the treatment of peptic ulcer disease, reflux esophagitis, and the Zollinger-Ellison syndrome. Although clinical experience with omeprazole is still limited, many controlled studies have established the short-term safety of this drug. We report the first case of a serious short-term adverse reaction with the use of omeprazole: hemolytic anemia. The patient developed weakness, lethargy, and shortness of breath 2 days after starting therapy with omeprazole. Two weeks after the initiation of therapy, her hematocrit had decreased from 44.1% to 20.4%, and she had a positive direct Coombs antiglobulin test and an elevated indirect bilirubin. After she discontinued the omeprazole, her hemoglobin and hematocrit gradually returned to normal. The mechanism by which omeprazole caused the patient's hemolytic anemia is uncertain, but physicians should be alerted to this possible adverse effect."],"offsets":[[56,1115]]}],"entities":[{"id":"24004","type":"Disease","text":["Hemolytic anemia"],"offsets":[[0,16]],"normalized":[{"db_name":"MESH","db_id":"D000743"}]},{"id":"24005","type":"Chemical","text":["omeprazole"],"offsets":[[44,54]],"normalized":[{"db_name":"MESH","db_id":"D009853"}]},{"id":"24006","type":"Chemical","text":["Omeprazole"],"offsets":[[56,66]],"normalized":[{"db_name":"MESH","db_id":"D009853"}]},{"id":"24007","type":"Disease","text":["peptic ulcer disease"],"offsets":[[238,258]],"normalized":[{"db_name":"MESH","db_id":"D010437"}]},{"id":"24008","type":"Disease","text":["reflux esophagitis"],"offsets":[[260,278]],"normalized":[{"db_name":"MESH","db_id":"D005764"}]},{"id":"24009","type":"Disease","text":["Zollinger-Ellison 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breath"],"offsets":[[614,633]],"normalized":[{"db_name":"MESH","db_id":"D004417"}]},{"id":"24015","type":"Chemical","text":["omeprazole"],"offsets":[[669,679]],"normalized":[{"db_name":"MESH","db_id":"D009853"}]},{"id":"24016","type":"Chemical","text":["bilirubin"],"offsets":[[854,863]],"normalized":[{"db_name":"MESH","db_id":"D001663"}]},{"id":"24017","type":"Chemical","text":["omeprazole"],"offsets":[[892,902]],"normalized":[{"db_name":"MESH","db_id":"D009853"}]},{"id":"24018","type":"Chemical","text":["omeprazole"],"offsets":[[987,997]],"normalized":[{"db_name":"MESH","db_id":"D009853"}]},{"id":"24019","type":"Disease","text":["hemolytic anemia"],"offsets":[[1019,1035]],"normalized":[{"db_name":"MESH","db_id":"D000743"}]}],"events":[],"coreferences":[],"relations":[{"id":"24020","type":"CID","arg1_id":"24005","arg2_id":"24014","normalized":[]},{"id":"24021","type":"CID","arg1_id":"24006","arg2_id":"24014","normalized":[]},{"id":"24022","type":"CID","arg1_id":"24010","arg2_id":"24014","normalized":[]},{"id":"24023","type":"CID","arg1_id":"24011","arg2_id":"24014","normalized":[]},{"id":"24024","type":"CID","arg1_id":"24015","arg2_id":"24014","normalized":[]},{"id":"24025","type":"CID","arg1_id":"24017","arg2_id":"24014","normalized":[]},{"id":"24026","type":"CID","arg1_id":"24018","arg2_id":"24014","normalized":[]},{"id":"24027","type":"CID","arg1_id":"24005","arg2_id":"24004","normalized":[]},{"id":"24028","type":"CID","arg1_id":"24005","arg2_id":"24012","normalized":[]},{"id":"24029","type":"CID","arg1_id":"24005","arg2_id":"24019","normalized":[]},{"id":"24030","type":"CID","arg1_id":"24006","arg2_id":"24004","normalized":[]},{"id":"24031","type":"CID","arg1_id":"24006","arg2_id":"24012","normalized":[]},{"id":"24032","type":"CID","arg1_id":"24006","arg2_id":"24019","normalized":[]},{"id":"24033","type":"CID","arg1_id":"24010","arg2_id":"24004","normalized":[]},{"id":"24034","type":"CID","arg1_id":"24010","arg2_id":"24012","normalized":[]},{"id":"24035","type":"CID","arg1_id":"24010","arg2_id":"24019","normalized":[]},{"id":"24036","type":"CID","arg1_id":"24011","arg2_id":"24004","normalized":[]},{"id":"24037","type":"CID","arg1_id":"24011","arg2_id":"24012","normalized":[]},{"id":"24038","type":"CID","arg1_id":"24011","arg2_id":"24019","normalized":[]},{"id":"24039","type":"CID","arg1_id":"24015","arg2_id":"24004","normalized":[]},{"id":"24040","type":"CID","arg1_id":"24015","arg2_id":"24012","normalized":[]},{"id":"24041","type":"CID","arg1_id":"24015","arg2_id":"24019","normalized":[]},{"id":"24042","type":"CID","arg1_id":"24017","arg2_id":"24004","normalized":[]},{"id":"24043","type":"CID","arg1_id":"24017","arg2_id":"24012","normalized":[]},{"id":"24044","type":"CID","arg1_id":"24017","arg2_id":"24019","normalized":[]},{"id":"24045","type":"CID","arg1_id":"24018","arg2_id":"24004","normalized":[]},{"id":"24046","type":"CID","arg1_id":"24018","arg2_id":"24012","normalized":[]},{"id":"24047","type":"CID","arg1_id":"24018","arg2_id":"24019","normalized":[]},{"id":"24048","type":"CID","arg1_id":"24005","arg2_id":"24013","normalized":[]},{"id":"24049","type":"CID","arg1_id":"24006","arg2_id":"24013","normalized":[]},{"id":"24050","type":"CID","arg1_id":"24010","arg2_id":"24013","normalized":[]},{"id":"24051","type":"CID","arg1_id":"24011","arg2_id":"24013","normalized":[]},{"id":"24052","type":"CID","arg1_id":"24015","arg2_id":"24013","normalized":[]},{"id":"24053","type":"CID","arg1_id":"24017","arg2_id":"24013","normalized":[]},{"id":"24054","type":"CID","arg1_id":"24018","arg2_id":"24013","normalized":[]}]}
{"id":"24055","document_id":"8387218","passages":[{"id":"24056","type":"title","text":["The use and toxicity of didanosine (ddI) in HIV antibody-positive individuals intolerant to zidovudine (AZT)"],"offsets":[[0,108]]},{"id":"24057","type":"abstract","text":["One hundred and fifty-one patients intolerant to zidovudine (AZT) received didanosine (ddI) to a maximum dose of 12.5 mg\/kg\/day. Patient response was assessed using changes in CD4+ lymphocyte subset count, HIV p24 antigen, weight, and quality of life. Seventy patients developed major opportunistic infections whilst on therapy; this was the first AIDS diagnosis in 17. Only minor changes in CD4+ lymphocyte subset count were observed in AIDS patients, although a more significant rise occurred in those with earlier stages of disease. Of those positive for p24 antigen at the commencement of the study 67% showed a positive response, and this was most likely in those with CD4+ lymphocyte subset counts above 100 mm3. A positive weight response was seen in 16% of patients. Most patients showed improvement in individual parameters and global score of quality of life. Adverse reactions possibly attributable to didanosine were common. The most common side-effect was diarrhoea, which resulted in cessation of therapy in 19 individuals. Peripheral neuropathy occurred in 12 patients and pancreatitis in six. Thirteen patients developed a raised serum amylase without abdominal pain. Seven patients developed glucose tolerance curves characteristic of diabetes but these were mild, did not require treatment and returned to normal on ceasing didanosine."],"offsets":[[109,1462]]}],"entities":[{"id":"24058","type":"Disease","text":["toxicity"],"offsets":[[12,20]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"24059","type":"Chemical","text":["didanosine"],"offsets":[[24,34]],"normalized":[{"db_name":"MESH","db_id":"D016049"}]},{"id":"24060","type":"Chemical","text":["ddI"],"offsets":[[36,39]],"normalized":[{"db_name":"MESH","db_id":"D016049"}]},{"id":"24061","type":"Disease","text":["HIV antibody-positive"],"offsets":[[44,65]],"normalized":[{"db_name":"MESH","db_id":"D015658"}]},{"id":"24062","type":"Chemical","text":["zidovudine"],"offsets":[[92,102]],"normalized":[{"db_name":"MESH","db_id":"D015215"}]},{"id":"24063","type":"Chemical","text":["AZT"],"offsets":[[104,107]],"normalized":[{"db_name":"MESH","db_id":"D015215"}]},{"id":"24064","type":"Chemical","text":["zidovudine"],"offsets":[[158,168]],"normalized":[{"db_name":"MESH","db_id":"D015215"}]},{"id":"24065","type":"Chemical","text":["AZT"],"offsets":[[170,173]],"normalized":[{"db_name":"MESH","db_id":"D015215"}]},{"id":"24066","type":"Chemical","text":["didanosine"],"offsets":[[184,194]],"normalized":[{"db_name":"MESH","db_id":"D016049"}]},{"id":"24067","type":"Chemical","text":["ddI"],"offsets":[[196,199]],"normalized":[{"db_name":"MESH","db_id":"D016049"}]},{"id":"24068","type":"Disease","text":["opportunistic infections"],"offsets":[[394,418]],"normalized":[{"db_name":"MESH","db_id":"D009894"}]},{"id":"24069","type":"Disease","text":["AIDS"],"offsets":[[457,461]],"normalized":[{"db_name":"MESH","db_id":"D000163"}]},{"id":"24070","type":"Disease","text":["AIDS"],"offsets":[[547,551]],"normalized":[{"db_name":"MESH","db_id":"D000163"}]},{"id":"24071","type":"Chemical","text":["didanosine"],"offsets":[[1022,1032]],"normalized":[{"db_name":"MESH","db_id":"D016049"}]},{"id":"24072","type":"Disease","text":["diarrhoea"],"offsets":[[1078,1087]],"normalized":[{"db_name":"MESH","db_id":"D003967"}]},{"id":"24073","type":"Disease","text":["Peripheral neuropathy"],"offsets":[[1147,1168]],"normalized":[{"db_name":"MESH","db_id":"D010523"}]},{"id":"24074","type":"Disease","text":["pancreatitis"],"offsets":[[1197,1209]],"normalized":[{"db_name":"MESH","db_id":"D010195"}]},{"id":"24075","type":"Disease","text":["abdominal pain"],"offsets":[[1277,1291]],"normalized":[{"db_name":"MESH","db_id":"D015746"}]},{"id":"24076","type":"Disease","text":["glucose tolerance curves"],"offsets":[[1318,1342]],"normalized":[{"db_name":"MESH","db_id":"D018149"}]},{"id":"24077","type":"Disease","text":["diabetes"],"offsets":[[1361,1369]],"normalized":[{"db_name":"MESH","db_id":"D003920"}]},{"id":"24078","type":"Chemical","text":["didanosine"],"offsets":[[1451,1461]],"normalized":[{"db_name":"MESH","db_id":"D016049"}]}],"events":[],"coreferences":[],"relations":[{"id":"24079","type":"CID","arg1_id":"24059","arg2_id":"24076","normalized":[]},{"id":"24080","type":"CID","arg1_id":"24060","arg2_id":"24076","normalized":[]},{"id":"24081","type":"CID","arg1_id":"24066","arg2_id":"24076","normalized":[]},{"id":"24082","type":"CID","arg1_id":"24067","arg2_id":"24076","normalized":[]},{"id":"24083","type":"CID","arg1_id":"24071","arg2_id":"24076","normalized":[]},{"id":"24084","type":"CID","arg1_id":"24078","arg2_id":"24076","normalized":[]},{"id":"24085","type":"CID","arg1_id":"24059","arg2_id":"24073","normalized":[]},{"id":"24086","type":"CID","arg1_id":"24060","arg2_id":"24073","normalized":[]},{"id":"24087","type":"CID","arg1_id":"24066","arg2_id":"24073","normalized":[]},{"id":"24088","type":"CID","arg1_id":"24067","arg2_id":"24073","normalized":[]},{"id":"24089","type":"CID","arg1_id":"24071","arg2_id":"24073","normalized":[]},{"id":"24090","type":"CID","arg1_id":"24078","arg2_id":"24073","normalized":[]},{"id":"24091","type":"CID","arg1_id":"24059","arg2_id":"24072","normalized":[]},{"id":"24092","type":"CID","arg1_id":"24060","arg2_id":"24072","normalized":[]},{"id":"24093","type":"CID","arg1_id":"24066","arg2_id":"24072","normalized":[]},{"id":"24094","type":"CID","arg1_id":"24067","arg2_id":"24072","normalized":[]},{"id":"24095","type":"CID","arg1_id":"24071","arg2_id":"24072","normalized":[]},{"id":"24096","type":"CID","arg1_id":"24078","arg2_id":"24072","normalized":[]},{"id":"24097","type":"CID","arg1_id":"24059","arg2_id":"24074","normalized":[]},{"id":"24098","type":"CID","arg1_id":"24060","arg2_id":"24074","normalized":[]},{"id":"24099","type":"CID","arg1_id":"24066","arg2_id":"24074","normalized":[]},{"id":"24100","type":"CID","arg1_id":"24067","arg2_id":"24074","normalized":[]},{"id":"24101","type":"CID","arg1_id":"24071","arg2_id":"24074","normalized":[]},{"id":"24102","type":"CID","arg1_id":"24078","arg2_id":"24074","normalized":[]}]}
{"id":"24103","document_id":"20698227","passages":[{"id":"24104","type":"title","text":["Can angiogenesis be a target of treatment for ribavirin associated hemolytic anemia?"],"offsets":[[0,84]]},{"id":"24105","type":"abstract","text":["BACKGROUND\/AIMS: Recently ribavirin has been found to inhibit angiogenesis and a number of angiogenesis inhibitors such as sunitinib and sorafenib have been found to cause acute hemolysis. We aimed to investigate whether there is a relation between hemoglobin, haptoglobin and angiogenesis soluble markers which are modifiable and can help in developing strategies against anemia. METHODS: Fourteen patients chronically infected with hepatitis C virus were treated by pegylated interferon alpha 2a and ribavirin. Serum hemoglobin, haptoglobin and angiogenesis markers of vascular endothelial growth factor and angiopoetin-2 were investigated before and after therapy. RESULTS: We observed a significant decrease in haptoglobin levels at the end of the treatment period. Hemoglobin levels also decreased but insignificantly by treatment. In contrast with the literature, serum levels of angiogenesis factors did not change significantly by pegylated interferon and ribavirin therapy. We found no correlation of angiogenesis soluble markers with either hemoglobin or haptoglobin. CONCLUSION: This is the first study in the literature investigating a link between angiogenesis soluble markers and ribavirin induced anemia in patients with hepatitis C and we could not find any relation. Future research with larger number of patients is needed to find out modifiable factors that will improve the safety of ribavirin therapy."],"offsets":[[85,1507]]}],"entities":[{"id":"24106","type":"Chemical","text":["ribavirin"],"offsets":[[46,55]],"normalized":[{"db_name":"MESH","db_id":"D012254"}]},{"id":"24107","type":"Disease","text":["hemolytic anemia"],"offsets":[[67,83]],"normalized":[{"db_name":"MESH","db_id":"D000743"}]},{"id":"24108","type":"Chemical","text":["ribavirin"],"offsets":[[111,120]],"normalized":[{"db_name":"MESH","db_id":"D012254"}]},{"id":"24109","type":"Chemical","text":["sunitinib"],"offsets":[[208,217]],"normalized":[{"db_name":"MESH","db_id":"C473478"}]},{"id":"24110","type":"Chemical","text":["sorafenib"],"offsets":[[222,231]],"normalized":[{"db_name":"MESH","db_id":"C471405"}]},{"id":"24111","type":"Disease","text":["hemolysis"],"offsets":[[263,272]],"normalized":[{"db_name":"MESH","db_id":"D006461"}]},{"id":"24112","type":"Disease","text":["anemia"],"offsets":[[458,464]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]},{"id":"24113","type":"Disease","text":["chronically infected with hepatitis C virus"],"offsets":[[493,536]],"normalized":[{"db_name":"MESH","db_id":"D019698"}]},{"id":"24114","type":"Chemical","text":["pegylated interferon alpha 2a"],"offsets":[[553,582]],"normalized":[{"db_name":"MESH","db_id":"C100416"}]},{"id":"24115","type":"Chemical","text":["ribavirin"],"offsets":[[587,596]],"normalized":[{"db_name":"MESH","db_id":"D012254"}]},{"id":"24116","type":"Chemical","text":["pegylated interferon"],"offsets":[[1024,1044]],"normalized":[{"db_name":"MESH","db_id":"C417083"}]},{"id":"24117","type":"Chemical","text":["ribavirin"],"offsets":[[1049,1058]],"normalized":[{"db_name":"MESH","db_id":"D012254"}]},{"id":"24118","type":"Chemical","text":["ribavirin"],"offsets":[[1279,1288]],"normalized":[{"db_name":"MESH","db_id":"D012254"}]},{"id":"24119","type":"Disease","text":["anemia"],"offsets":[[1297,1303]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]},{"id":"24120","type":"Disease","text":["hepatitis C"],"offsets":[[1321,1332]],"normalized":[{"db_name":"MESH","db_id":"D019698"}]},{"id":"24121","type":"Chemical","text":["ribavirin"],"offsets":[[1489,1498]],"normalized":[{"db_name":"MESH","db_id":"D012254"}]}],"events":[],"coreferences":[],"relations":[{"id":"24122","type":"CID","arg1_id":"24110","arg2_id":"24111","normalized":[]},{"id":"24123","type":"CID","arg1_id":"24109","arg2_id":"24111","normalized":[]}]}
{"id":"24124","document_id":"20477932","passages":[{"id":"24125","type":"title","text":["Cocaine causes memory and learning impairments in rats: involvement of nuclear factor kappa B and oxidative stress, and prevention by topiramate."],"offsets":[[0,145]]},{"id":"24126","type":"abstract","text":["Different mechanisms have been suggested for cocaine toxicity including an increase in oxidative stress but the association between oxidative status in the brain and cocaine induced-behaviour is poorly understood. Nuclear factor kappa B (NFkappaB) is a sensor of oxidative stress and participates in memory formation that could be involved in drug toxicity and addiction mechanisms. Therefore NFkappaB activity, oxidative stress, neuronal nitric oxide synthase (nNOS) activity, spatial learning and memory as well as the effect of topiramate, a previously proposed therapy for cocaine addiction, were evaluated in an experimental model of cocaine administration in rats. NFkappaB activity was decreased in the frontal cortex of cocaine treated rats, as well as GSH concentration and glutathione peroxidase activity in the hippocampus, whereas nNOS activity in the hippocampus was increased. Memory retrieval of experiences acquired prior to cocaine administration was impaired and negatively correlated with NFkappaB activity in the frontal cortex. In contrast, learning of new tasks was enhanced and correlated with the increase of nNOS activity and the decrease of glutathione peroxidase. These results provide evidence for a possible mechanistic role of oxidative and nitrosative stress and NFkappaB in the alterations induced by cocaine. Topiramate prevented all the alterations observed, showing novel neuroprotective properties."],"offsets":[[146,1580]]}],"entities":[{"id":"24127","type":"Chemical","text":["Cocaine"],"offsets":[[0,7]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"24128","type":"Disease","text":["memory and learning impairments"],"offsets":[[15,46]],"normalized":[{"db_name":"MESH","db_id":"D008569"},{"db_name":"MESH","db_id":"D007859"}]},{"id":"24129","type":"Disease","text":["memory","impairments"],"offsets":[[15,21],[35,46]],"normalized":[{"db_name":"MESH","db_id":"D008569"}]},{"id":"24130","type":"Disease","text":["learning impairments"],"offsets":[[26,46]],"normalized":[{"db_name":"MESH","db_id":"D007859"}]},{"id":"24131","type":"Chemical","text":["topiramate"],"offsets":[[134,144]],"normalized":[{"db_name":"MESH","db_id":"C052342"}]},{"id":"24132","type":"Chemical","text":["cocaine"],"offsets":[[191,198]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"24133","type":"Disease","text":["toxicity"],"offsets":[[199,207]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"24134","type":"Chemical","text":["cocaine"],"offsets":[[312,319]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"24135","type":"Disease","text":["toxicity"],"offsets":[[494,502]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"24136","type":"Chemical","text":["nitric oxide"],"offsets":[[585,597]],"normalized":[{"db_name":"MESH","db_id":"D009569"}]},{"id":"24137","type":"Chemical","text":["topiramate"],"offsets":[[677,687]],"normalized":[{"db_name":"MESH","db_id":"C052342"}]},{"id":"24138","type":"Disease","text":["cocaine addiction"],"offsets":[[723,740]],"normalized":[{"db_name":"MESH","db_id":"D019970"}]},{"id":"24139","type":"Chemical","text":["cocaine"],"offsets":[[785,792]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"24140","type":"Chemical","text":["cocaine"],"offsets":[[874,881]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"24141","type":"Chemical","text":["GSH"],"offsets":[[907,910]],"normalized":[{"db_name":"MESH","db_id":"D005978"}]},{"id":"24142","type":"Chemical","text":["glutathione"],"offsets":[[929,940]],"normalized":[{"db_name":"MESH","db_id":"D005978"}]},{"id":"24143","type":"Chemical","text":["cocaine"],"offsets":[[1087,1094]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"24144","type":"Chemical","text":["glutathione"],"offsets":[[1313,1324]],"normalized":[{"db_name":"MESH","db_id":"D005978"}]},{"id":"24145","type":"Chemical","text":["cocaine"],"offsets":[[1479,1486]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"24146","type":"Chemical","text":["Topiramate"],"offsets":[[1488,1498]],"normalized":[{"db_name":"MESH","db_id":"C052342"}]}],"events":[],"coreferences":[],"relations":[{"id":"24147","type":"CID","arg1_id":"24127","arg2_id":"24128","normalized":[]},{"id":"24148","type":"CID","arg1_id":"24127","arg2_id":"24130","normalized":[]},{"id":"24149","type":"CID","arg1_id":"24132","arg2_id":"24128","normalized":[]},{"id":"24150","type":"CID","arg1_id":"24132","arg2_id":"24130","normalized":[]},{"id":"24151","type":"CID","arg1_id":"24134","arg2_id":"24128","normalized":[]},{"id":"24152","type":"CID","arg1_id":"24134","arg2_id":"24130","normalized":[]},{"id":"24153","type":"CID","arg1_id":"24139","arg2_id":"24128","normalized":[]},{"id":"24154","type":"CID","arg1_id":"24139","arg2_id":"24130","normalized":[]},{"id":"24155","type":"CID","arg1_id":"24140","arg2_id":"24128","normalized":[]},{"id":"24156","type":"CID","arg1_id":"24140","arg2_id":"24130","normalized":[]},{"id":"24157","type":"CID","arg1_id":"24143","arg2_id":"24128","normalized":[]},{"id":"24158","type":"CID","arg1_id":"24143","arg2_id":"24130","normalized":[]},{"id":"24159","type":"CID","arg1_id":"24145","arg2_id":"24128","normalized":[]},{"id":"24160","type":"CID","arg1_id":"24145","arg2_id":"24130","normalized":[]},{"id":"24161","type":"CID","arg1_id":"24127","arg2_id":"24128","normalized":[]},{"id":"24162","type":"CID","arg1_id":"24127","arg2_id":"24129","normalized":[]},{"id":"24163","type":"CID","arg1_id":"24132","arg2_id":"24128","normalized":[]},{"id":"24164","type":"CID","arg1_id":"24132","arg2_id":"24129","normalized":[]},{"id":"24165","type":"CID","arg1_id":"24134","arg2_id":"24128","normalized":[]},{"id":"24166","type":"CID","arg1_id":"24134","arg2_id":"24129","normalized":[]},{"id":"24167","type":"CID","arg1_id":"24139","arg2_id":"24128","normalized":[]},{"id":"24168","type":"CID","arg1_id":"24139","arg2_id":"24129","normalized":[]},{"id":"24169","type":"CID","arg1_id":"24140","arg2_id":"24128","normalized":[]},{"id":"24170","type":"CID","arg1_id":"24140","arg2_id":"24129","normalized":[]},{"id":"24171","type":"CID","arg1_id":"24143","arg2_id":"24128","normalized":[]},{"id":"24172","type":"CID","arg1_id":"24143","arg2_id":"24129","normalized":[]},{"id":"24173","type":"CID","arg1_id":"24145","arg2_id":"24128","normalized":[]},{"id":"24174","type":"CID","arg1_id":"24145","arg2_id":"24129","normalized":[]}]}
{"id":"24175","document_id":"9495837","passages":[{"id":"24176","type":"title","text":["Antinociceptive and antiamnesic properties of the presynaptic cholinergic amplifier PG-9."],"offsets":[[0,89]]},{"id":"24177","type":"abstract","text":["The antinociceptive effect of 3 alpha-tropyl 2-(p-bromophenyl)propionate [(+\/-)-PG-9] (10-40 mg kg-1 s.c.; 30-60 mg kg-1 p.o.; 10-30 mg kg-1 i.v.; 10-30 micrograms\/mouse i.c.v.) was examined in mice, rats and guinea pigs by use of the hot-plate, abdominal-constriction, tail-flick and paw-pressure tests. (+\/-)-PG-9 antinociception peaked 15 min after injection and then slowly diminished. The antinociception produced by (+\/-)-PG-9 was prevented by the unselective muscarinic antagonist atropine, the M1-selective antagonists pirenzepine and dicyclomine and the acetylcholine depletor hemicholinium-3, but not by the opioid antagonist naloxone, the gamma-aminobutyric acidB antagonist 3-aminopropyl-diethoxy-methyl-phosphinic acid, the H3 agonist R-(alpha)-methylhistamine, the D2 antagonist quinpirole, the 5-hydroxytryptamine4 antagonist 2-methoxy-4-amino-5-chlorobenzoic acid 2-(diethylamino)ethyl ester hydrochloride, the 5-hydroxytryptamin1A antagonist 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine hydrobromide and the polyamines depletor reserpine. Based on these data, it can be postulated that (+\/-)-PG-9 exerted an antinociceptive effect mediated by a central potentiation of cholinergic transmission. (+\/-)-PG-9 (10-40 mg kg-1 i.p.) was able to prevent amnesia induced by scopolamine (1 mg kg-1 i.p.) and dicyclomine (2 mg kg-1 i.p.) in the mouse passive-avoidance test. Affinity profiles of (+\/-)-PG-9 for muscarinic receptor subtypes, determined by functional studies (rabbit vas deferens for M1, guinea pig atrium for M2, guinea pig ileum for M3 and immature guinea pig uterus for putative M4), have shown an M4\/M1 selectivity ratio of 10.2 that might be responsible for the antinociception and the anti-amnesic effect induced by (+\/-)-PG-9 through an increase in acetylcholine extracellular levels. In the antinociceptive and antiamnesic dose range, (+\/-)-PG-9 did not impair mouse performance evaluated by the rota-rod test and Animex apparatus."],"offsets":[[90,2063]]}],"entities":[{"id":"24178","type":"Chemical","text":["PG-9"],"offsets":[[84,88]],"normalized":[{"db_name":"MESH","db_id":"C087567"}]},{"id":"24179","type":"Chemical","text":["3 alpha-tropyl 2-(p-bromophenyl)propionate"],"offsets":[[120,162]],"normalized":[{"db_name":"MESH","db_id":"C087567"}]},{"id":"24180","type":"Chemical","text":["PG-9"],"offsets":[[170,174]],"normalized":[{"db_name":"MESH","db_id":"C087567"}]},{"id":"24181","type":"Chemical","text":["PG-9"],"offsets":[[401,405]],"normalized":[{"db_name":"MESH","db_id":"C087567"}]},{"id":"24182","type":"Chemical","text":["PG-9"],"offsets":[[518,522]],"normalized":[{"db_name":"MESH","db_id":"C087567"}]},{"id":"24183","type":"Chemical","text":["atropine"],"offsets":[[578,586]],"normalized":[{"db_name":"MESH","db_id":"D001285"}]},{"id":"24184","type":"Chemical","text":["pirenzepine"],"offsets":[[617,628]],"normalized":[{"db_name":"MESH","db_id":"D010890"}]},{"id":"24185","type":"Chemical","text":["dicyclomine"],"offsets":[[633,644]],"normalized":[{"db_name":"MESH","db_id":"D004025"}]},{"id":"24186","type":"Chemical","text":["acetylcholine"],"offsets":[[653,666]],"normalized":[{"db_name":"MESH","db_id":"D000109"}]},{"id":"24187","type":"Chemical","text":["hemicholinium-3"],"offsets":[[676,691]],"normalized":[{"db_name":"MESH","db_id":"D006426"}]},{"id":"24188","type":"Chemical","text":["naloxone"],"offsets":[[726,734]],"normalized":[{"db_name":"MESH","db_id":"D009270"}]},{"id":"24189","type":"Chemical","text":["gamma-aminobutyric acidB"],"offsets":[[740,764]],"normalized":[{"db_name":"MESH","db_id":"D005680"}]},{"id":"24190","type":"Chemical","text":["3-aminopropyl-diethoxy-methyl-phosphinic acid"],"offsets":[[776,821]],"normalized":[{"db_name":"MESH","db_id":"C066430"}]},{"id":"24191","type":"Chemical","text":["R-(alpha)-methylhistamine"],"offsets":[[838,863]],"normalized":[{"db_name":"MESH","db_id":"C069357"}]},{"id":"24192","type":"Chemical","text":["quinpirole"],"offsets":[[883,893]],"normalized":[{"db_name":"MESH","db_id":"D019257"}]},{"id":"24193","type":"Chemical","text":["5-hydroxytryptamine4"],"offsets":[[899,919]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"24194","type":"Chemical","text":["2-methoxy-4-amino-5-chlorobenzoic acid 2-(diethylamino)ethyl ester"],"offsets":[[931,997]],"normalized":[{"db_name":"MESH","db_id":"C072790"}]},{"id":"24195","type":"Chemical","text":["5-hydroxytryptamin1A"],"offsets":[[1017,1037]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"24196","type":"Chemical","text":["1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine"],"offsets":[[1049,1105]],"normalized":[{"db_name":"MESH","db_id":"C058895"}]},{"id":"24197","type":"Chemical","text":["reserpine"],"offsets":[[1147,1156]],"normalized":[{"db_name":"MESH","db_id":"D012110"}]},{"id":"24198","type":"Chemical","text":["PG-9"],"offsets":[[1211,1215]],"normalized":[{"db_name":"MESH","db_id":"C087567"}]},{"id":"24199","type":"Chemical","text":["PG-9"],"offsets":[[1320,1324]],"normalized":[{"db_name":"MESH","db_id":"C087567"}]},{"id":"24200","type":"Disease","text":["amnesia"],"offsets":[[1366,1373]],"normalized":[{"db_name":"MESH","db_id":"D000647"}]},{"id":"24201","type":"Chemical","text":["scopolamine"],"offsets":[[1385,1396]],"normalized":[{"db_name":"MESH","db_id":"D012601"}]},{"id":"24202","type":"Chemical","text":["dicyclomine"],"offsets":[[1418,1429]],"normalized":[{"db_name":"MESH","db_id":"D004025"}]},{"id":"24203","type":"Chemical","text":["PG-9"],"offsets":[[1511,1515]],"normalized":[{"db_name":"MESH","db_id":"C087567"}]},{"id":"24204","type":"Disease","text":["amnesic"],"offsets":[[1820,1827]],"normalized":[{"db_name":"MESH","db_id":"D000647"}]},{"id":"24205","type":"Chemical","text":["PG-9"],"offsets":[[1852,1856]],"normalized":[{"db_name":"MESH","db_id":"C087567"}]},{"id":"24206","type":"Chemical","text":["acetylcholine"],"offsets":[[1880,1893]],"normalized":[{"db_name":"MESH","db_id":"D000109"}]},{"id":"24207","type":"Chemical","text":["PG-9"],"offsets":[[1973,1977]],"normalized":[{"db_name":"MESH","db_id":"C087567"}]}],"events":[],"coreferences":[],"relations":[{"id":"24208","type":"CID","arg1_id":"24201","arg2_id":"24200","normalized":[]},{"id":"24209","type":"CID","arg1_id":"24201","arg2_id":"24204","normalized":[]},{"id":"24210","type":"CID","arg1_id":"24185","arg2_id":"24200","normalized":[]},{"id":"24211","type":"CID","arg1_id":"24185","arg2_id":"24204","normalized":[]},{"id":"24212","type":"CID","arg1_id":"24202","arg2_id":"24200","normalized":[]},{"id":"24213","type":"CID","arg1_id":"24202","arg2_id":"24204","normalized":[]}]}
{"id":"24214","document_id":"1468485","passages":[{"id":"24215","type":"title","text":["Hyperbaric oxygen therapy for control of intractable cyclophosphamide-induced hemorrhagic cystitis."],"offsets":[[0,99]]},{"id":"24216","type":"abstract","text":["We report a case of intractable hemorrhagic cystitis due to cyclophosphamide therapy for Wegener's granulomatosis. Conservative treatment, including bladder irrigation with physiological saline and instillation of prostaglandin F2 alpha, failed to totally control hemorrhage. We then used hyperbaric oxygen at an absolute pressure of 2 atm, 5 days a week for 8 consecutive weeks. The bleeding ceased completely by the end of treatment and the patient remained free of hematuria thereafter. No side effect was noted during the course of therapy. In future, this form of therapy can offer a safe alternative in the treatment of cyclophosphamide-induced hemorrhagic cystitis."],"offsets":[[100,772]]}],"entities":[{"id":"24217","type":"Chemical","text":["oxygen"],"offsets":[[11,17]],"normalized":[{"db_name":"MESH","db_id":"D010100"}]},{"id":"24218","type":"Chemical","text":["cyclophosphamide"],"offsets":[[53,69]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"24219","type":"Disease","text":["hemorrhagic cystitis"],"offsets":[[78,98]],"normalized":[{"db_name":"MESH","db_id":"D006470"},{"db_name":"MESH","db_id":"D003556"}]},{"id":"24220","type":"Disease","text":["hemorrhagic"],"offsets":[[78,89]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"24221","type":"Disease","text":["cystitis"],"offsets":[[90,98]],"normalized":[{"db_name":"MESH","db_id":"D003556"}]},{"id":"24222","type":"Disease","text":["hemorrhagic cystitis"],"offsets":[[132,152]],"normalized":[{"db_name":"MESH","db_id":"D006470"},{"db_name":"MESH","db_id":"D003556"}]},{"id":"24223","type":"Disease","text":["hemorrhagic"],"offsets":[[132,143]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"24224","type":"Disease","text":["cystitis"],"offsets":[[144,152]],"normalized":[{"db_name":"MESH","db_id":"D003556"}]},{"id":"24225","type":"Chemical","text":["cyclophosphamide"],"offsets":[[160,176]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"24226","type":"Disease","text":["Wegener's granulomatosis"],"offsets":[[189,213]],"normalized":[{"db_name":"MESH","db_id":"D014890"}]},{"id":"24227","type":"Chemical","text":["prostaglandin F2 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{"id":"24281","document_id":"1009330","passages":[{"id":"24282","type":"title","text":["Further studies on effects of irrigation solutions on rat bladders."],"offsets":[[0,67]]},{"id":"24283","type":"abstract","text":["Further studies on the effects of certain irrigating fluids on the rat bladder for 18 hours are reported. The results have shown that the degradation product p-choloroaniline is not a significant factor in chlorhexidine-digluconate associated erosive cystitis. A high percentage of kanamycin-colistin and povidone-iodine irrigations were associated with erosive cystitis and suggested a possible complication with human usage. Picloxydine irrigations appeared to have a lower incidence of erosive cystitis but further studies would have to be performed before it could be recommended for use in urological procedures."],"offsets":[[68,685]]}],"entities":[{"id":"24284","type":"Chemical","text":["p-choloroaniline"],"offsets":[[226,242]],"normalized":[{"db_name":"MESH","db_id":"C004658"}]},{"id":"24285","type":"Chemical","text":["chlorhexidine-digluconate"],"offsets":[[274,299]],"normalized":[{"db_name":"MESH","db_id":"C010882"}]},{"id":"24286","type":"Disease","text":["cystitis"],"offsets":[[319,327]],"normalized":[{"db_name":"MESH","db_id":"D003556"}]},{"id":"24287","type":"Chemical","text":["kanamycin"],"offsets":[[350,359]],"normalized":[{"db_name":"MESH","db_id":"D007612"}]},{"id":"24288","type":"Chemical","text":["colistin"],"offsets":[[360,368]],"normalized":[{"db_name":"MESH","db_id":"D003091"}]},{"id":"24289","type":"Chemical","text":["povidone-iodine"],"offsets":[[373,388]],"normalized":[{"db_name":"MESH","db_id":"D011206"}]},{"id":"24290","type":"Disease","text":["cystitis"],"offsets":[[430,438]],"normalized":[{"db_name":"MESH","db_id":"D003556"}]},{"id":"24291","type":"Chemical","text":["Picloxydine"],"offsets":[[495,506]],"normalized":[{"db_name":"MESH","db_id":"C005253"}]},{"id":"24292","type":"Disease","text":["cystitis"],"offsets":[[565,573]],"normalized":[{"db_name":"MESH","db_id":"D003556"}]}],"events":[],"coreferences":[],"relations":[{"id":"24293","type":"CID","arg1_id":"24285","arg2_id":"24286","normalized":[]},{"id":"24294","type":"CID","arg1_id":"24285","arg2_id":"24290","normalized":[]},{"id":"24295","type":"CID","arg1_id":"24285","arg2_id":"24292","normalized":[]},{"id":"24296","type":"CID","arg1_id":"24288","arg2_id":"24286","normalized":[]},{"id":"24297","type":"CID","arg1_id":"24288","arg2_id":"24290","normalized":[]},{"id":"24298","type":"CID","arg1_id":"24288","arg2_id":"24292","normalized":[]},{"id":"24299","type":"CID","arg1_id":"24287","arg2_id":"24286","normalized":[]},{"id":"24300","type":"CID","arg1_id":"24287","arg2_id":"24290","normalized":[]},{"id":"24301","type":"CID","arg1_id":"24287","arg2_id":"24292","normalized":[]},{"id":"24302","type":"CID","arg1_id":"24289","arg2_id":"24286","normalized":[]},{"id":"24303","type":"CID","arg1_id":"24289","arg2_id":"24290","normalized":[]},{"id":"24304","type":"CID","arg1_id":"24289","arg2_id":"24292","normalized":[]}]}
{"id":"24305","document_id":"347884","passages":[{"id":"24306","type":"title","text":["Clinical experiences in an open and a double-blind trial."],"offsets":[[0,57]]},{"id":"24307","type":"abstract","text":["A total of sixty patients were trated with bromperidol first in open conditions (20 patients), then on a double blind basis (40 patients) with haloperidol as the reference substance. The open study lasted for four weeks; the drug was administrated in the form of 1 mg tablets. The daily dose (initial dose: 1 mg; mean dose at the end of the trial: 4.47 mg) was always administered in one single dose. Nineteen patients finished the trial, and in 18 cases the therapeutic result was considered very good to good. These results were confirmed by statistical analysis. Nine patients exhibited mild to moderate extrapyramidal concomitant symptoms; no other side effects were observed. The results of detailed laboratory tests and evaluations of various quantitative and qualitative tolerability parameters were not indicative of toxic effects. In the double blind study with haloperidol, both substances were found to be highly effective in the treatment of psychotic syndromes belonging predominantly to the schizophrenia group. Certain clues, including the onset of action, seem to be indicative of the superiority of bromperidol. No differences were observed with respect to side effects and general tolerability."],"offsets":[[58,1270]]}],"entities":[{"id":"24308","type":"Chemical","text":["bromperidol"],"offsets":[[101,112]],"normalized":[{"db_name":"MESH","db_id":"C006820"}]},{"id":"24309","type":"Chemical","text":["haloperidol"],"offsets":[[201,212]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"24310","type":"Disease","text":["extrapyramidal concomitant symptoms"],"offsets":[[665,700]],"normalized":[{"db_name":"MESH","db_id":"D001480"}]},{"id":"24311","type":"Chemical","text":["haloperidol"],"offsets":[[929,940]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"24312","type":"Disease","text":["psychotic syndromes belonging predominantly to the schizophrenia group"],"offsets":[[1012,1082]],"normalized":[{"db_name":"MESH","db_id":"D019967"}]},{"id":"24313","type":"Chemical","text":["bromperidol"],"offsets":[[1174,1185]],"normalized":[{"db_name":"MESH","db_id":"C006820"}]}],"events":[],"coreferences":[],"relations":[{"id":"24314","type":"CID","arg1_id":"24309","arg2_id":"24310","normalized":[]},{"id":"24315","type":"CID","arg1_id":"24311","arg2_id":"24310","normalized":[]},{"id":"24316","type":"CID","arg1_id":"24308","arg2_id":"24310","normalized":[]},{"id":"24317","type":"CID","arg1_id":"24313","arg2_id":"24310","normalized":[]}]}
{"id":"24318","document_id":"20667451","passages":[{"id":"24319","type":"title","text":["Curcumin ameliorates cognitive dysfunction and oxidative damage in phenobarbitone and carbamazepine administered rats."],"offsets":[[0,118]]},{"id":"24320","type":"abstract","text":["The antiepileptic drugs, phenobarbitone and carbamazepine are well known to cause cognitive impairment on chronic use. The increase in free radical generation has been implicated as one of the important mechanisms of cognitive impairment by antiepileptic drugs. Curcumin has shown antioxidant, anti-inflammatory and neuro-protective properties. Therefore, the present study was carried out to investigate the effect of chronic curcumin administration on phenobarbitone- and carbamazepine-induced cognitive impairment and oxidative stress in rats. Pharmacokinetic interactions of curcumin with phenobarbitone and carbamazepine were also studied. Vehicle\/drugs were administered daily for 21days to male Wistar rats. Passive avoidance paradigm and elevated plus maze test were used to assess cognitive function. At the end of study period, serum phenobarbitone and carbamazepine, whole brain malondialdehyde and reduced glutathione levels were estimated. The administration of phenobarbitone and carbamazepine for 21days caused a significant impairment of learning and memory as well as an increased oxidative stress. Concomitant curcumin administration prevented the cognitive impairment and decreased the increased oxidative stress induced by these antiepileptic drugs. Curcumin co-administration did not cause any significant alteration in the serum concentrations of both phenobarbitone as well as carbamazepine. These results show that curcumin has beneficial effect in mitigating the deterioration of cognitive functions and oxidative damage in rats treated with phenobarbitone and carbamazepine without significantly altering their serum concentrations. The findings suggest that curcumin can be considered as a potential safe and effective adjuvant to phenobarbitone and carbamazepine therapy in preventing cognitive impairment associated with these drugs."],"offsets":[[119,1981]]}],"entities":[{"id":"24321","type":"Chemical","text":["Curcumin"],"offsets":[[0,8]],"normalized":[{"db_name":"MESH","db_id":"D003474"}]},{"id":"24322","type":"Disease","text":["cognitive 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Administration of 50 mg\/kg PDTC (low-dose) did not exert major effects on the development of a status epilepticus or the mortality rate. In vehicle-treated rats, status epilepticus caused pronounced neuronal damage in the piriform cortex comprising both pyramidal cells and interneurons. Low-dose PDTC treatment almost completely protected from lesions in the piriform cortex. A significant decrease in neuronal density of the hippocampal hilar formation was identified in vehicle- and PDTC-treated rats following status epilepticus. In conclusion, the NF-kappaB inhibitor and antioxidant PDTC protected the piriform cortex, whereas it did not affect hilar neuronal loss. These data might indicate that the generation of reactive oxygen species and activation of NF-kappaB plays a more central role in seizure-associated neuronal damage in the temporal cortex as compared to the hippocampal hilus. However, future investigations are necessary to exactly analyze the biochemical mechanisms by which PDTC exerted its beneficial effects in the piriform cortex."],"offsets":[[102,1790]]}],"entities":[{"id":"24504","type":"Chemical","text":["Pyrrolidine dithiocarbamate"],"offsets":[[0,27]],"normalized":[{"db_name":"MESH","db_id":"C020972"}]},{"id":"24505","type":"Chemical","text":["pilocarpine"],"offsets":[[64,75]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"24506","type":"Disease","text":["status epilepticus"],"offsets":[[76,94]],"normalized":[{"db_name":"MESH","db_id":"D013226"}]},{"id":"24507","type":"Chemical","text":["Pyrrolidine 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{"id":"24549","document_id":"16330293","passages":[{"id":"24550","type":"title","text":["Safety profile of a nicotine lozenge compared with that of nicotine gum in adult smokers with underlying medical conditions: a 12-week, randomized, open-label study."],"offsets":[[0,165]]},{"id":"24551","type":"abstract","text":["BACKGROUND: Nicotine polacrilex lozenges deliver 25% to 27% more nicotine compared with equivalent doses of nicotine polacrilex gum. The increased nicotine exposure from the lozenge has raised questions about the relative safety of the lozenge and gum. OBJECTIVE: The objective of this study was to compare the safety profiles of the 4-mg nicotine lozenge and 4-mg nicotine gum in smokers with selected label-restricted diseases. METHODS: This was a multicenter, randomized, open-label study in adult smokers with heart disease, hypertension not controlled by medication, and\/or diabetes mellitus. Patients were randomized in a 1:1 ratio to receive the 4-mg nicotine lozenge or 4-mg nicotine gum. Safety assessments were made at baseline and at 2, 4, 6, and 12 weeks after the start of product use. RESULTS: Nine hundred one patients were randomized to treatment, 447 who received the lozenge and 454 who received the gum (safety population). The majority were women (52.7%). Patients' mean age was 53.9 years, their mean weight was 193.9 pounds, and they smoked a mean of 25.2 cigarettes per day at baseline. Five hundred fifty-three patients, 264 taking the lozenge and 289 taking the gum, used the study product for > or =4 days per week during the first 2 weeks (evaluable population). The nicotine lozenge and nicotine gum were equally well tolerated, despite increased nicotine exposure from the lozenge. The incidence of adverse events in the 2 groups was similar during the first 2 weeks of product use (evaluation population: 55.3% lozenge, 54.7% gum), as well as during the entire study (safety population: 63.8% and 58.6%, respectively). Stratification of patients by sex, age, extent of concurrent smoking, extent of product use, and severity of adverse events revealed no clinically significant differences between the lozenge and gum. The most common adverse events were nausea (17.2% and 16.1%; 95% CI, -3.7 to 6.0), hiccups (10.7% and 6.6%; 95% CI, 0.5 to 7.8), and headache (8.7% and 9.9%; 95% Cl, -5.0 to 2.6). Serious adverse events were reported in 11 and 13 patients in the respective groups. Fewer than 6% of patients in either group were considered by the investigator to have a worsening of their overall disease condition during the study. The majority of patients (>60%) experienced no change in their disease status from baseline. CONCLUSION: The 4-mg nicotine lozenge and 4-mg nicotine gum had comparable safety profiles in these patients with label-restricted medical conditions."],"offsets":[[166,2674]]}],"entities":[{"id":"24552","type":"Chemical","text":["nicotine"],"offsets":[[20,28]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"24553","type":"Chemical","text":["nicotine"],"offsets":[[59,67]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"24554","type":"Chemical","text":["Nicotine"],"offsets":[[178,186]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"24555","type":"Chemical","text":["nicotine"],"offsets":[[231,239]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"24556","type":"Chemical","text":["nicotine"],"offsets":[[274,282]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"24557","type":"Chemical","text":["nicotine"],"offsets":[[313,321]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"24558","type":"Chemical","text":["nicotine"],"offsets":[[505,513]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"24559","type":"Chemical","text":["nicotine"],"offsets":[[531,539]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"24560","type":"Disease","text":["heart 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{"id":"24618","document_id":"14568327","passages":[{"id":"24619","type":"title","text":["Development of levodopa-induced dyskinesias in parkinsonian monkeys may depend upon rate of symptom onset and\/or duration of symptoms."],"offsets":[[0,134]]},{"id":"24620","type":"abstract","text":["Levodopa-induced dyskinesias (LIDs) present a major problem for the long-term management of Parkinson's disease (PD) patients. Due to the interdependence of risk factors in clinical populations, it is difficult to independently examine factors that may influence the development of LIDs. Using macaque monkeys with different types of MPTP-induced parkinsonism, the current study evaluated the degree to which rate of symptom progression, symptom severity, and response to and duration of levodopa therapy may be involved in the development of LIDs. Monkeys with acute (short-term) MPTP exposure, rapid symptom onset and short symptom duration prior to initiation of levodopa therapy developed dyskinesia between 11 and 24 days of daily levodopa administration. In contrast, monkeys with long-term MPTP exposure, slow symptom progression and\/or long symptom duration prior to initiation of levodopa therapy were more resistant to developing LIDs (e.g., dyskinesia developed no sooner than 146 days of chronic levodopa administration). All animals were similarly symptomatic at the start of levodopa treatment and had similar therapeutic responses to the drug. These data suggest distinct differences in the propensity to develop LIDs in monkeys with different rates of symptom progression or symptom durations prior to levodopa and demonstrate the value of these models for further studying the pathophysiology of LIDs."],"offsets":[[135,1553]]}],"entities":[{"id":"24621","type":"Chemical","text":["levodopa"],"offsets":[[15,23]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"24622","type":"Disease","text":["dyskinesias"],"offsets":[[32,43]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"24623","type":"Disease","text":["parkinsonian"],"offsets":[[47,59]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"24624","type":"Chemical","text":["Levodopa"],"offsets":[[135,143]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"24625","type":"Disease","text":["dyskinesias"],"offsets":[[152,163]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"24626","type":"Disease","text":["LIDs"],"offsets":[[165,169]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"24627","type":"Disease","text":["Parkinson's 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{"id":"24740","document_id":"11250767","passages":[{"id":"24741","type":"title","text":["Propylthiouracil-induced perinuclear-staining antineutrophil cytoplasmic autoantibody-positive vasculitis in conjunction with pericarditis."],"offsets":[[0,139]]},{"id":"24742","type":"abstract","text":["OBJECTIVE: To describe a case of propylthiouracil-induced vasculitis manifesting with pericarditis. METHODS: We present the first case report of a woman with hyperthyroidism treated with propylthiouracil in whom a syndrome of pericarditis, fever, and glomerulonephritis developed. Serologic testing and immunologic studies were done, and a pericardial biopsy was performed. RESULTS: A 25-year-old woman with Graves' disease had a febrile illness and evidence of pericarditis, which was confirmed by biopsy. Serologic evaluation revealed the presence of perinuclear-staining antineutrophil cytoplasmic autoantibodies (pANCA) against myeloperoxidase (MPO). Propylthiouracil therapy was withdrawn, and she was treated with a 1-month course of prednisone, which alleviated her symptoms. A literature review revealed no prior reports of pericarditis in anti-MPO pANCA-positive vasculitis associated with propylthio- uracil therapy. CONCLUSION: Pericarditis may be the initial manifestation of drug-induced vasculitis attributable to propylthio- uracil therapy."],"offsets":[[140,1195]]}],"entities":[{"id":"24743","type":"Chemical","text":["Propylthiouracil"],"offsets":[[0,16]],"normalized":[{"db_name":"MESH","db_id":"D011441"}]},{"id":"24744","type":"Disease","text":["vasculitis"],"offsets":[[95,105]],"normalized":[{"db_name":"MESH","db_id":"D014657"}]},{"id":"24745","type":"Disease","text":["pericarditis"],"offsets":[[126,138]],"normalized":[{"db_name":"MESH","db_id":"D010493"}]},{"id":"24746","type":"Chemical","text":["propylthiouracil"],"offsets":[[173,189]],"normalized":[{"db_name":"MESH","db_id":"D011441"}]},{"id":"24747","type":"Disease","text":["vasculitis"],"offsets":[[198,208]],"normalized":[{"db_name":"MESH","db_id":"D014657"}]},{"id":"24748","type":"Disease","text":["pericarditis"],"offsets":[[226,238]],"normalized":[{"db_name":"MESH","db_id":"D010493"}]},{"id":"24749","type":"Disease","text":["hyperthyroidism"],"offsets":[[298,313]],"normalized":[{"db_name":"MESH","db_id":"D006980"}]},{"id":"24750","type":"Chemical","text":["propylthiouracil"],"offsets":[[327,343]],"normalized":[{"db_name":"MESH","db_id":"D011441"}]},{"id":"24751","type":"Disease","text":["pericarditis"],"offsets":[[366,378]],"normalized":[{"db_name":"MESH","db_id":"D010493"}]},{"id":"24752","type":"Disease","text":["fever"],"offsets":[[380,385]],"normalized":[{"db_name":"MESH","db_id":"D005334"}]},{"id":"24753","type":"Disease","text":["glomerulonephritis"],"offsets":[[391,409]],"normalized":[{"db_name":"MESH","db_id":"D005921"}]},{"id":"24754","type":"Disease","text":["Graves' 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{"id":"24819","document_id":"11206082","passages":[{"id":"24820","type":"title","text":["Two mouse lines selected for differential sensitivities to beta-carboline-induced seizures are also differentially sensitive to various pharmacological effects of other GABA(A) receptor ligands."],"offsets":[[0,194]]},{"id":"24821","type":"abstract","text":["Two mouse lines were selectively bred according to their sensitivity (BS line) or resistance (BR line) to seizures induced by a single i.p. injection of methyl beta-carboline-3-carboxylate (beta-CCM), an inverse agonist of the GABA(A) receptor benzodiazepine site. Our aim was to characterize both lines' sensitivities to various physiological effects of other ligands of the GABA(A) receptor. We measured diazepam-induced anxiolysis with the elevated plus-maze test, diazepam-induced sedation by recording the vigilance states, and picrotoxin- and pentylenetetrazol-induced seizures after i.p. injections. Results presented here show that the differential sensitivities of BS and BR lines to beta-CCM can be extended to diazepam, picrotoxin, and pentylenetetrazol, suggesting a genetic selection of a general sensitivity and resistance to several ligands of the GABA(A) receptor."],"offsets":[[195,1075]]}],"entities":[{"id":"24822","type":"Chemical","text":["beta-carboline"],"offsets":[[59,73]],"normalized":[{"db_name":"MESH","db_id":"C036150"}]},{"id":"24823","type":"Disease","text":["seizures"],"offsets":[[82,90]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"24824","type":"Chemical","text":["GABA"],"offsets":[[169,173]],"normalized":[{"db_name":"MESH","db_id":"D005680"}]},{"id":"24825","type":"Disease","text":["seizures"],"offsets":[[301,309]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"24826","type":"Chemical","text":["methyl beta-carboline-3-carboxylate"],"offsets":[[348,383]],"normalized":[{"db_name":"MESH","db_id":"C036150"}]},{"id":"24827","type":"Chemical","text":["beta-CCM"],"offsets":[[385,393]],"normalized":[{"db_name":"MESH","db_id":"C036150"}]},{"id":"24828","type":"Chemical","text":["GABA"],"offsets":[[422,426]],"normalized":[{"db_name":"MESH","db_id":"D005680"}]},{"id":"24829","type":"Chemical","text":["benzodiazepine"],"offsets":[[439,453]],"normalized":[{"db_name":"MESH","db_id":"D001569"}]},{"id":"24830","type":"Chemical","text":["GABA"],"offsets":[[571,575]],"normalized":[{"db_name":"MESH","db_id":"D005680"}]},{"id":"24831","type":"Chemical","text":["diazepam"],"offsets":[[601,609]],"normalized":[{"db_name":"MESH","db_id":"D003975"}]},{"id":"24832","type":"Chemical","text":["diazepam"],"offsets":[[663,671]],"normalized":[{"db_name":"MESH","db_id":"D003975"}]},{"id":"24833","type":"Chemical","text":["picrotoxin"],"offsets":[[728,738]],"normalized":[{"db_name":"MESH","db_id":"D010852"}]},{"id":"24834","type":"Chemical","text":["pentylenetetrazol"],"offsets":[[744,761]],"normalized":[{"db_name":"MESH","db_id":"D010433"}]},{"id":"24835","type":"Disease","text":["seizures"],"offsets":[[770,778]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"24836","type":"Chemical","text":["beta-CCM"],"offsets":[[888,896]],"normalized":[{"db_name":"MESH","db_id":"C036150"}]},{"id":"24837","type":"Chemical","text":["diazepam"],"offsets":[[916,924]],"normalized":[{"db_name":"MESH","db_id":"D003975"}]},{"id":"24838","type":"Chemical","text":["picrotoxin"],"offsets":[[926,936]],"normalized":[{"db_name":"MESH","db_id":"D010852"}]},{"id":"24839","type":"Chemical","text":["pentylenetetrazol"],"offsets":[[942,959]],"normalized":[{"db_name":"MESH","db_id":"D010433"}]},{"id":"24840","type":"Chemical","text":["GABA"],"offsets":[[1058,1062]],"normalized":[{"db_name":"MESH","db_id":"D005680"}]}],"events":[],"coreferences":[],"relations":[{"id":"24841","type":"CID","arg1_id":"24833","arg2_id":"24823","normalized":[]},{"id":"24842","type":"CID","arg1_id":"24833","arg2_id":"24825","normalized":[]},{"id":"24843","type":"CID","arg1_id":"24833","arg2_id":"24835","normalized":[]},{"id":"24844","type":"CID","arg1_id":"24838","arg2_id":"24823","normalized":[]},{"id":"24845","type":"CID","arg1_id":"24838","arg2_id":"24825","normalized":[]},{"id":"24846","type":"CID","arg1_id":"24838","arg2_id":"24835","normalized":[]},{"id":"24847","type":"CID","arg1_id":"24834","arg2_id":"24823","normalized":[]},{"id":"24848","type":"CID","arg1_id":"24834","arg2_id":"24825","normalized":[]},{"id":"24849","type":"CID","arg1_id":"24834","arg2_id":"24835","normalized":[]},{"id":"24850","type":"CID","arg1_id":"24839","arg2_id":"24823","normalized":[]},{"id":"24851","type":"CID","arg1_id":"24839","arg2_id":"24825","normalized":[]},{"id":"24852","type":"CID","arg1_id":"24839","arg2_id":"24835","normalized":[]},{"id":"24853","type":"CID","arg1_id":"24822","arg2_id":"24823","normalized":[]},{"id":"24854","type":"CID","arg1_id":"24822","arg2_id":"24825","normalized":[]},{"id":"24855","type":"CID","arg1_id":"24822","arg2_id":"24835","normalized":[]},{"id":"24856","type":"CID","arg1_id":"24826","arg2_id":"24823","normalized":[]},{"id":"24857","type":"CID","arg1_id":"24826","arg2_id":"24825","normalized":[]},{"id":"24858","type":"CID","arg1_id":"24826","arg2_id":"24835","normalized":[]},{"id":"24859","type":"CID","arg1_id":"24827","arg2_id":"24823","normalized":[]},{"id":"24860","type":"CID","arg1_id":"24827","arg2_id":"24825","normalized":[]},{"id":"24861","type":"CID","arg1_id":"24827","arg2_id":"24835","normalized":[]},{"id":"24862","type":"CID","arg1_id":"24836","arg2_id":"24823","normalized":[]},{"id":"24863","type":"CID","arg1_id":"24836","arg2_id":"24825","normalized":[]},{"id":"24864","type":"CID","arg1_id":"24836","arg2_id":"24835","normalized":[]}]}
{"id":"24865","document_id":"11027905","passages":[{"id":"24866","type":"title","text":["Analgesic effect of intravenous ketamine in cancer patients on morphine therapy: a randomized, controlled, double-blind, crossover, double-dose study."],"offsets":[[0,150]]},{"id":"24867","type":"abstract","text":["Pain not responsive to morphine is often problematic. Animal and clinical studies have suggested that N-methyl-D-aspartate (NMDA) antagonists, such as ketamine, may be effective in improving opioid analgesia in difficult pain syndromes, such as neuropathic pain. A slow bolus of subhypnotic doses of ketamine (0.25 mg\/kg or 0.50 mg\/kg) was given to 10 cancer patients whose pain was unrelieved by morphine in a randomized, double-blind, crossover, double-dose study. Pain intensity on a 0 to 10 numerical scale; nausea and vomiting, drowsiness, confusion, and dry mouth, using a scale from 0 to 3 (not at all, slight, a lot, awful); Mini-Mental State Examination (MMSE) (0-30); and arterial pressure were recorded before administration of drugs (T0) and after 30 minutes (T30), 60 minutes (T60), 120 minutes (T120), and 180 minutes (T180). Ketamine, but not saline solution, significantly reduced the pain intensity in almost all the patients at both doses. This effect was more relevant in patients treated with higher doses. Hallucinations occurred in 4 patients, and an unpleasant sensation (\"empty head\") was also reported by 2 patients. These episodes reversed after the administration of diazepam 1 mg intravenously. Significant increases in drowsiness were reported in patients treated with ketamine in both groups and were more marked with ketamine 0.50 mg\/kg. A significant difference in MMSE was observed at T30 in patients who received 0.50 mg\/kg of ketamine. Ketamine can improve morphine analgesia in difficult pain syndromes, such as neuropathic pain. However, the occurrence of central adverse effects should be taken into account, especially when using higher doses. This observation should be tested in studies of prolonged ketamine administration."],"offsets":[[151,1916]]}],"entities":[{"id":"24868","type":"Chemical","text":["ketamine"],"offsets":[[32,40]],"normalized":[{"db_name":"MESH","db_id":"D007649"}]},{"id":"24869","type":"Disease","text":["cancer"],"offsets":[[44,50]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"24870","type":"Chemical","text":["morphine"],"offsets":[[63,71]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"24871","type":"Disease","text":["Pain"],"offsets":[[151,155]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"24872","type":"Chemical","text":["morphine"],"offsets":[[174,182]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"24873","type":"Chemical","text":["N-methyl-D-aspartate"],"offsets":[[253,273]],"normalized":[{"db_name":"MESH","db_id":"D016202"}]},{"id":"24874","type":"Chemical","text":["NMDA"],"offsets":[[275,279]],"normalized":[{"db_name":"MESH","db_id":"D016202"}]},{"id":"24875","type":"Chemical","text":["ketamine"],"offsets":[[302,310]],"normalized":[{"db_name":"MESH","db_id":"D007649"}]},{"id":"24876","type":"Disease","text":["pain"],"offsets":[[372,376]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"24877","type":"Disease","text":["neuropathic pain"],"offsets":[[396,412]],"normalized":[{"db_name":"MESH","db_id":"D009437"}]},{"id":"24878","type":"Chemical","text":["ketamine"],"offsets":[[451,459]],"normalized":[{"db_name":"MESH","db_id":"D007649"}]},{"id":"24879","type":"Disease","text":["cancer"],"offsets":[[503,509]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"24880","type":"Disease","text":["pain"],"offsets":[[525,529]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"24881","type":"Chemical","text":["morphine"],"offsets":[[548,556]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"24882","type":"Disease","text":["Pain"],"offsets":[[618,622]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"24883","type":"Disease","text":["nausea"],"offsets":[[663,669]],"normalized":[{"db_name":"MESH","db_id":"D009325"}]},{"id":"24884","type":"Disease","text":["vomiting"],"offsets":[[674,682]],"normalized":[{"db_name":"MESH","db_id":"D014839"}]},{"id":"24885","type":"Disease","text":["confusion"],"offsets":[[696,705]],"normalized":[{"db_name":"MESH","db_id":"D003221"}]},{"id":"24886","type":"Disease","text":["dry mouth"],"offsets":[[711,720]],"normalized":[{"db_name":"MESH","db_id":"D014987"}]},{"id":"24887","type":"Chemical","text":["Ketamine"],"offsets":[[991,999]],"normalized":[{"db_name":"MESH","db_id":"D007649"}]},{"id":"24888","type":"Disease","text":["pain"],"offsets":[[1052,1056]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"24889","type":"Disease","text":["Hallucinations"],"offsets":[[1178,1192]],"normalized":[{"db_name":"MESH","db_id":"D006212"}]},{"id":"24890","type":"Chemical","text":["diazepam"],"offsets":[[1345,1353]],"normalized":[{"db_name":"MESH","db_id":"D003975"}]},{"id":"24891","type":"Chemical","text":["ketamine"],"offsets":[[1449,1457]],"normalized":[{"db_name":"MESH","db_id":"D007649"}]},{"id":"24892","type":"Chemical","text":["ketamine"],"offsets":[[1499,1507]],"normalized":[{"db_name":"MESH","db_id":"D007649"}]},{"id":"24893","type":"Chemical","text":["ketamine"],"offsets":[[1612,1620]],"normalized":[{"db_name":"MESH","db_id":"D007649"}]},{"id":"24894","type":"Chemical","text":["Ketamine"],"offsets":[[1622,1630]],"normalized":[{"db_name":"MESH","db_id":"D007649"}]},{"id":"24895","type":"Chemical","text":["morphine"],"offsets":[[1643,1651]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"24896","type":"Disease","text":["pain"],"offsets":[[1675,1679]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"24897","type":"Disease","text":["neuropathic pain"],"offsets":[[1699,1715]],"normalized":[{"db_name":"MESH","db_id":"D009437"}]},{"id":"24898","type":"Chemical","text":["ketamine"],"offsets":[[1892,1900]],"normalized":[{"db_name":"MESH","db_id":"D007649"}]}],"events":[],"coreferences":[],"relations":[{"id":"24899","type":"CID","arg1_id":"24868","arg2_id":"24889","normalized":[]},{"id":"24900","type":"CID","arg1_id":"24875","arg2_id":"24889","normalized":[]},{"id":"24901","type":"CID","arg1_id":"24878","arg2_id":"24889","normalized":[]},{"id":"24902","type":"CID","arg1_id":"24887","arg2_id":"24889","normalized":[]},{"id":"24903","type":"CID","arg1_id":"24891","arg2_id":"24889","normalized":[]},{"id":"24904","type":"CID","arg1_id":"24892","arg2_id":"24889","normalized":[]},{"id":"24905","type":"CID","arg1_id":"24893","arg2_id":"24889","normalized":[]},{"id":"24906","type":"CID","arg1_id":"24894","arg2_id":"24889","normalized":[]},{"id":"24907","type":"CID","arg1_id":"24898","arg2_id":"24889","normalized":[]}]}
{"id":"24908","document_id":"9334596","passages":[{"id":"24909","type":"title","text":["Endocrine screening in 1,022 men with erectile dysfunction: clinical significance and cost-effective strategy."],"offsets":[[0,110]]},{"id":"24910","type":"abstract","text":["PURPOSE: We reviewed the results of serum testosterone and prolactin determination in 1,022 patients referred because of erectile dysfunction and compared the data with history, results of physical examination, other etiological investigations and effects of endocrine therapy to refine the rules of cost-effective endocrine screening and to pinpoint actual responsibility for hormonal abnormalities. MATERIALS AND METHODS: Testosterone and prolactin were determined by radioimmunoassay. Every patient was screened for testosterone and 451 were screened for prolactin on the basis of low sexual desire, gynecomastia or testosterone less than 4 ng.\/ml. Determination was repeated in case of abnormal first results. Prolactin results were compared with those of a previous personal cohort of 1,340 patients with erectile dysfunction and systematic prolactin determination. Main clinical criteria tested regarding efficiency in hormone determination were low sexual desire, small testes and gynecomastia. Endocrine therapy consisted of testosterone heptylate or human chorionic gonadotropin for hypogonadism and bromocriptine for hyperprolactinemia. RESULTS: Testosterone was less than 3 ng.\/ml. in 107 patients but normal in 40% at repeat determination. The prevalence of repeatedly low testosterone increased with age (4% before age 50 years and 9% 50 years or older). Two pituitary tumors were discovered after testosterone determination. Most of the other low testosterone levels seemed to result from nonorganic hypothalamic dysfunction because of normal serum luteinizing hormone and prolactin and to have only a small role in erectile dysfunction (definite improvement in only 16 of 44 [36%] after androgen therapy, normal morning or nocturnal erections in 30% and definite vasculogenic contributions in 42%). Determining testosterone only in cases of low sexual desire or abnormal physical examination would have missed 40% of the cases with low testosterone, including 37% of those subsequently improved by androgen therapy. Prolactin exceeded 20 ng.\/ml. in 5 men and was normal in 2 at repeat determination. Only 1 prolactinoma was discovered. These data are lower than those we found during the last 2 decades (overall prolactin greater than 20 ng.\/ml. in 1.86% of 1,821 patients, prolactinomas in 7, 0.38%). Bromocriptine was definitely effective in cases with prolactin greater than 35 ng.\/ml. (8 of 12 compared to only 9 of 22 cases with prolactin between 20 and 35 ng.\/ml.). Testosterone was low in less than 50% of cases with prolactin greater than 35 ng.\/ml. CONCLUSIONS: Low prevalences and effects of low testosterone and high prolactin in erectile dysfunction cannot justify their routine determination. However, cost-effective screening strategies recommended so far missed 40 to 50% of cases improved with endocrine therapy and the pituitary tumors. We now advocate that before age 50 years testosterone be determined only in cases of low sexual desire and abnormal physical examination but that it be measured in all men older than 50 years. Prolactin should be determined only in cases of low sexual desire, gynecomastia and\/or testosterone less than 4 ng.\/ml."],"offsets":[[111,3292]]}],"entities":[{"id":"24911","type":"Disease","text":["erectile dysfunction"],"offsets":[[38,58]],"normalized":[{"db_name":"MESH","db_id":"D007172"}]},{"id":"24912","type":"Chemical","text":["testosterone"],"offsets":[[153,165]],"normalized":[{"db_name":"MESH","db_id":"D013739"}]},{"id":"24913","type":"Disease","text":["erectile dysfunction"],"offsets":[[232,252]],"normalized":[{"db_name":"MESH","db_id":"D007172"}]},{"id":"24914","type":"Chemical","text":["Testosterone"],"offsets":[[535,547]],"normalized":[{"db_name":"MESH","db_id":"D013739"}]},{"id":"24915","type":"Chemical","text":["testosterone"],"offsets":[[630,642]],"normalized":[{"db_name":"MESH","db_id":"D013739"}]},{"id":"24916","type":"Disease","text":["low sexual desire"],"offsets":[[695,712]],"normalized":[{"db_name":"MESH","db_id":"D020018"}]},{"id":"24917","type":"Disease","text":["gynecomastia"],"offsets":[[714,726]],"normalized":[{"db_name":"MESH","db_id":"D006177"}]},{"id":"24918","type":"Chemical","text":["testosterone"],"offsets":[[730,742]],"normalized":[{"db_name":"MESH","db_id":"D013739"}]},{"id":"24919","type":"Disease","text":["erectile dysfunction"],"offsets":[[921,941]],"normalized":[{"db_name":"MESH","db_id":"D007172"}]},{"id":"24920","type":"Disease","text":["low sexual desire"],"offsets":[[1063,1080]],"normalized":[{"db_name":"MESH","db_id":"D020018"}]},{"id":"24921","type":"Disease","text":["gynecomastia"],"offsets":[[1099,1111]],"normalized":[{"db_name":"MESH","db_id":"D006177"}]},{"id":"24922","type":"Chemical","text":["testosterone heptylate"],"offsets":[[1144,1166]],"normalized":[{"db_name":"MESH","db_id":"C004648"}]},{"id":"24923","type":"Disease","text":["hypogonadism"],"offsets":[[1203,1215]],"normalized":[{"db_name":"MESH","db_id":"D007006"}]},{"id":"24924","type":"Chemical","text":["bromocriptine"],"offsets":[[1220,1233]],"normalized":[{"db_name":"MESH","db_id":"D001971"}]},{"id":"24925","type":"Disease","text":["hyperprolactinemia"],"offsets":[[1238,1256]],"normalized":[{"db_name":"MESH","db_id":"D006966"}]},{"id":"24926","type":"Chemical","text":["Testosterone"],"offsets":[[1267,1279]],"normalized":[{"db_name":"MESH","db_id":"D013739"}]},{"id":"24927","type":"Chemical","text":["testosterone"],"offsets":[[1396,1408]],"normalized":[{"db_name":"MESH","db_id":"D013739"}]},{"id":"24928","type":"Disease","text":["pituitary tumors"],"offsets":[[1483,1499]],"normalized":[{"db_name":"MESH","db_id":"D010911"}]},{"id":"24929","type":"Chemical","text":["testosterone"],"offsets":[[1522,1534]],"normalized":[{"db_name":"MESH","db_id":"D013739"}]},{"id":"24930","type":"Chemical","text":["testosterone"],"offsets":[[1572,1584]],"normalized":[{"db_name":"MESH","db_id":"D013739"}]},{"id":"24931","type":"Disease","text":["hypothalamic dysfunction"],"offsets":[[1625,1649]],"normalized":[{"db_name":"MESH","db_id":"D007027"}]},{"id":"24932","type":"Disease","text":["erectile dysfunction"],"offsets":[[1741,1761]],"normalized":[{"db_name":"MESH","db_id":"D007172"}]},{"id":"24933","type":"Chemical","text":["testosterone"],"offsets":[[1937,1949]],"normalized":[{"db_name":"MESH","db_id":"D013739"}]},{"id":"24934","type":"Disease","text":["low sexual 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{"id":"25018","document_id":"8595686","passages":[{"id":"25019","type":"title","text":["Thiopentone pretreatment for propofol injection pain in ambulatory patients."],"offsets":[[0,76]]},{"id":"25020","type":"abstract","text":["This study investigated propofol injection pain in patients undergoing ambulatory anaesthesia. In a randomized, double-blind trial, 90 women were allocated to receive one of three treatments prior to induction of anaesthesia with propofol. Patients in Group C received 2 ml normal saline, Group L, 2 ml, lidocaine 2% (40 mg) and Group T, 2 ml thiopentone 2.5% (50 mg). Venous discomfort was assessed with a visual analogue scale (VAS) 5-15 sec after commencing propofol administration using an infusion pump (rate 1000 micrograms.kg-1.min-1). Loss of consciousness occurred in 60-90 sec. Visual analogue scores (mean +\/- SD) during induction were lower in Groups L (3.3 +\/- 2.5) and T (4.1 +\/- 2.7) than in Group C (5.6 +\/- 2.3); P = 0.0031. The incidence of venous discomfort was lower in Group L (76.6%; P < 0.05) than in Group C (100%) but not different from Group T (90%). The VAS scores for recall of pain in the recovery room were correlated with the VAS scores during induction (r = 0.7045; P < 0.0001). Recovery room discharge times were similar: C (75.9 +\/- 19.4 min); L 73.6 +\/- 21.6 min); T (77.1 +\/- 18.9 min). Assessing their overall satisfaction, 89.7% would choose propofol anaesthesia again. We conclude that lidocaine reduces the incidence and severity of propofol injection pain in ambulatory patients whereas thiopentone only reduces its severity."],"offsets":[[77,1443]]}],"entities":[{"id":"25021","type":"Chemical","text":["Thiopentone"],"offsets":[[0,11]],"normalized":[{"db_name":"MESH","db_id":"D013874"}]},{"id":"25022","type":"Chemical","text":["propofol"],"offsets":[[29,37]],"normalized":[{"db_name":"MESH","db_id":"D015742"}]},{"id":"25023","type":"Disease","text":["pain"],"offsets":[[48,52]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"25024","type":"Chemical","text":["propofol"],"offsets":[[101,109]],"normalized":[{"db_name":"MESH","db_id":"D015742"}]},{"id":"25025","type":"Disease","text":["pain"],"offsets":[[120,124]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"25026","type":"Chemical","text":["propofol"],"offsets":[[307,315]],"normalized":[{"db_name":"MESH","db_id":"D015742"}]},{"id":"25027","type":"Chemical","text":["lidocaine"],"offsets":[[381,390]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"25028","type":"Chemical","text":["thiopentone"],"offsets":[[420,431]],"normalized":[{"db_name":"MESH","db_id":"D013874"}]},{"id":"25029","type":"Chemical","text":["propofol"],"offsets":[[538,546]],"normalized":[{"db_name":"MESH","db_id":"D015742"}]},{"id":"25030","type":"Disease","text":["Loss of consciousness"],"offsets":[[620,641]],"normalized":[{"db_name":"MESH","db_id":"D014474"}]},{"id":"25031","type":"Disease","text":["pain"],"offsets":[[983,987]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"25032","type":"Chemical","text":["propofol"],"offsets":[[1257,1265]],"normalized":[{"db_name":"MESH","db_id":"D015742"}]},{"id":"25033","type":"Chemical","text":["lidocaine"],"offsets":[[1302,1311]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"25034","type":"Chemical","text":["propofol"],"offsets":[[1350,1358]],"normalized":[{"db_name":"MESH","db_id":"D015742"}]},{"id":"25035","type":"Disease","text":["pain"],"offsets":[[1369,1373]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"25036","type":"Chemical","text":["thiopentone"],"offsets":[[1405,1416]],"normalized":[{"db_name":"MESH","db_id":"D013874"}]}],"events":[],"coreferences":[],"relations":[{"id":"25037","type":"CID","arg1_id":"25022","arg2_id":"25023","normalized":[]},{"id":"25038","type":"CID","arg1_id":"25022","arg2_id":"25025","normalized":[]},{"id":"25039","type":"CID","arg1_id":"25022","arg2_id":"25031","normalized":[]},{"id":"25040","type":"CID","arg1_id":"25022","arg2_id":"25035","normalized":[]},{"id":"25041","type":"CID","arg1_id":"25024","arg2_id":"25023","normalized":[]},{"id":"25042","type":"CID","arg1_id":"25024","arg2_id":"25025","normalized":[]},{"id":"25043","type":"CID","arg1_id":"25024","arg2_id":"25031","normalized":[]},{"id":"25044","type":"CID","arg1_id":"25024","arg2_id":"25035","normalized":[]},{"id":"25045","type":"CID","arg1_id":"25026","arg2_id":"25023","normalized":[]},{"id":"25046","type":"CID","arg1_id":"25026","arg2_id":"25025","normalized":[]},{"id":"25047","type":"CID","arg1_id":"25026","arg2_id":"25031","normalized":[]},{"id":"25048","type":"CID","arg1_id":"25026","arg2_id":"25035","normalized":[]},{"id":"25049","type":"CID","arg1_id":"25029","arg2_id":"25023","normalized":[]},{"id":"25050","type":"CID","arg1_id":"25029","arg2_id":"25025","normalized":[]},{"id":"25051","type":"CID","arg1_id":"25029","arg2_id":"25031","normalized":[]},{"id":"25052","type":"CID","arg1_id":"25029","arg2_id":"25035","normalized":[]},{"id":"25053","type":"CID","arg1_id":"25032","arg2_id":"25023","normalized":[]},{"id":"25054","type":"CID","arg1_id":"25032","arg2_id":"25025","normalized":[]},{"id":"25055","type":"CID","arg1_id":"25032","arg2_id":"25031","normalized":[]},{"id":"25056","type":"CID","arg1_id":"25032","arg2_id":"25035","normalized":[]},{"id":"25057","type":"CID","arg1_id":"25034","arg2_id":"25023","normalized":[]},{"id":"25058","type":"CID","arg1_id":"25034","arg2_id":"25025","normalized":[]},{"id":"25059","type":"CID","arg1_id":"25034","arg2_id":"25031","normalized":[]},{"id":"25060","type":"CID","arg1_id":"25034","arg2_id":"25035","normalized":[]}]}
{"id":"25061","document_id":"6466532","passages":[{"id":"25062","type":"title","text":["Comparison of i.v. glycopyrrolate and atropine in the prevention of bradycardia and arrhythmias following repeated doses of suxamethonium in children."],"offsets":[[0,150]]},{"id":"25063","type":"abstract","text":["The effectiveness of administration of glycopyrrolate 5 and 10 micrograms kg-1 and atropine 10 and 20 micrograms kg-1 i.v. immediately before the induction of anaesthesia, to prevent arrhythmia and bradycardia following repeated doses of suxamethonium in children, was studied. A control group was included for comparison with the lower dose range of glycopyrrolate and atropine. A frequency of bradycardia of 50% was noted in the control group, but this was not significantly different from the frequency with the active drugs. Bradycardia (defined as a decrease in heart rate to less than 50 beat min-1) was prevented when the larger dose of either active drug was used. It is recommended that either glycopyrrolate 10 micrograms kg-1 or atropine 20 micrograms kg-1 i.v. should immediately precede induction of anaesthesia, in children, if the repeated administration of suxamethonium is anticipated."],"offsets":[[151,1053]]}],"entities":[{"id":"25064","type":"Chemical","text":["glycopyrrolate"],"offsets":[[19,33]],"normalized":[{"db_name":"MESH","db_id":"D006024"}]},{"id":"25065","type":"Chemical","text":["atropine"],"offsets":[[38,46]],"normalized":[{"db_name":"MESH","db_id":"D001285"}]},{"id":"25066","type":"Disease","text":["bradycardia"],"offsets":[[68,79]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"25067","type":"Disease","text":["arrhythmias"],"offsets":[[84,95]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"25068","type":"Chemical","text":["suxamethonium"],"offsets":[[124,137]],"normalized":[{"db_name":"MESH","db_id":"D013390"}]},{"id":"25069","type":"Chemical","text":["glycopyrrolate"],"offsets":[[190,204]],"normalized":[{"db_name":"MESH","db_id":"D006024"}]},{"id":"25070","type":"Chemical","text":["atropine"],"offsets":[[234,242]],"normalized":[{"db_name":"MESH","db_id":"D001285"}]},{"id":"25071","type":"Disease","text":["arrhythmia"],"offsets":[[334,344]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"25072","type":"Disease","text":["bradycardia"],"offsets":[[349,360]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"25073","type":"Chemical","text":["suxamethonium"],"offsets":[[389,402]],"normalized":[{"db_name":"MESH","db_id":"D013390"}]},{"id":"25074","type":"Chemical","text":["glycopyrrolate"],"offsets":[[502,516]],"normalized":[{"db_name":"MESH","db_id":"D006024"}]},{"id":"25075","type":"Chemical","text":["atropine"],"offsets":[[521,529]],"normalized":[{"db_name":"MESH","db_id":"D001285"}]},{"id":"25076","type":"Disease","text":["bradycardia"],"offsets":[[546,557]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"25077","type":"Disease","text":["Bradycardia"],"offsets":[[680,691]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"25078","type":"Chemical","text":["glycopyrrolate"],"offsets":[[854,868]],"normalized":[{"db_name":"MESH","db_id":"D006024"}]},{"id":"25079","type":"Chemical","text":["atropine"],"offsets":[[891,899]],"normalized":[{"db_name":"MESH","db_id":"D001285"}]},{"id":"25080","type":"Chemical","text":["suxamethonium"],"offsets":[[1024,1037]],"normalized":[{"db_name":"MESH","db_id":"D013390"}]}],"events":[],"coreferences":[],"relations":[{"id":"25081","type":"CID","arg1_id":"25068","arg2_id":"25066","normalized":[]},{"id":"25082","type":"CID","arg1_id":"25068","arg2_id":"25072","normalized":[]},{"id":"25083","type":"CID","arg1_id":"25068","arg2_id":"25076","normalized":[]},{"id":"25084","type":"CID","arg1_id":"25068","arg2_id":"25077","normalized":[]},{"id":"25085","type":"CID","arg1_id":"25073","arg2_id":"25066","normalized":[]},{"id":"25086","type":"CID","arg1_id":"25073","arg2_id":"25072","normalized":[]},{"id":"25087","type":"CID","arg1_id":"25073","arg2_id":"25076","normalized":[]},{"id":"25088","type":"CID","arg1_id":"25073","arg2_id":"25077","normalized":[]},{"id":"25089","type":"CID","arg1_id":"25080","arg2_id":"25066","normalized":[]},{"id":"25090","type":"CID","arg1_id":"25080","arg2_id":"25072","normalized":[]},{"id":"25091","type":"CID","arg1_id":"25080","arg2_id":"25076","normalized":[]},{"id":"25092","type":"CID","arg1_id":"25080","arg2_id":"25077","normalized":[]}]}
{"id":"25093","document_id":"6308277","passages":[{"id":"25094","type":"title","text":["Reduction in caffeine toxicity by acetaminophen."],"offsets":[[0,48]]},{"id":"25095","type":"abstract","text":["A patient who allegedly consumed 100 tablets of an over-the-counter analgesic containing sodium acetylsalicylate, caffeine, and acetaminophen displayed no significant CNS stimulation despite the presence of 175 micrograms of caffeine per mL of serum. Because salicylates have been reported to augment the stimulatory effects of caffeine on the CNS, attention was focused on the possibility that the presence of acetaminophen (52 micrograms\/mL) reduced the CNS toxicity of caffeine. Studies in DBA\/2J mice showed that: 1) pretreatment with acetaminophen (100 mg\/kg) increased the interval between the administration of caffeine (300 to 450 mg\/kg IP) and the onset of fatal convulsions by a factor of about two; and 2) pretreatment with acetaminophen (75 mg\/kg) reduced the incidence of audiogenic seizures produced in the presence of caffeine (12.5 to 75 mg\/kg IP). The frequency of sound-induced seizures after 12.5 or 25 mg\/kg caffeine was reduced from 50 to 5% by acetaminophen. In the absence of caffeine, acetaminophen (up to 300 mg\/kg) did not modify the seizures induced by maximal electroshock and did not alter the convulsant dose of pentylenetetrezol in mice (tests performed by the Anticonvulsant Screening Project of NINCDS). Acetaminophen (up to 150 micrograms\/mL) did not retard the incorporation of radioactive adenosine into ATP in slices of rat cerebral cortex. Thus the mechanism by which acetaminophen antagonizes the actions of caffeine in the CNS remains unknown."],"offsets":[[49,1532]]}],"entities":[{"id":"25096","type":"Chemical","text":["caffeine"],"offsets":[[13,21]],"normalized":[{"db_name":"MESH","db_id":"D002110"}]},{"id":"25097","type":"Disease","text":["toxicity"],"offsets":[[22,30]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"25098","type":"Chemical","text":["acetaminophen"],"offsets":[[34,47]],"normalized":[{"db_name":"MESH","db_id":"D000082"}]},{"id":"25099","type":"Chemical","text":["sodium 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{"id":"25169","document_id":"2870085","passages":[{"id":"25170","type":"title","text":["Flestolol: an ultra-short-acting beta-adrenergic blocking agent."],"offsets":[[0,64]]},{"id":"25171","type":"abstract","text":["Flestolol (ACC-9089) is a nonselective, competitive, ultra-short-acting beta-adrenergic blocking agent, without any intrinsic sympathomimetic activity. Flestolol is metabolized by plasma esterases and has an elimination half-life of approximately 6.5 minutes. This agent was well tolerated in healthy volunteers at doses up to 100 micrograms\/kg\/min. In long-term infusion studies, flestolol was well tolerated at the effective beta-blocking dose (5 micrograms\/kg\/min) for up to seven days. Flestolol blood concentrations increased linearly with increasing dose and good correlation exists between blood concentrations of flestolol and beta-adrenergic blockade. Flestolol produced a dose-dependent attenuation of isoproterenol-induced tachycardia. Electrophysiologic and hemodynamic effects of flestolol are similar to those of other beta blockers. In contrast with other beta blockers, flestolol-induced effects reverse rapidly (within 30 minutes) following discontinuation because of its short half-life. Flestolol effectively reduced heart rate in patients with supraventricular tachyarrhythmia. In patients with unstable angina, flestolol infusion was found to be safe and effective in controlling chest pain. It is concluded that flestolol is a potent, well-tolerated, ultra-short-acting beta-adrenergic blocking agent. Use of flestolol in the critical care setting is currently undergoing investigation."],"offsets":[[65,1473]]}],"entities":[{"id":"25172","type":"Chemical","text":["Flestolol"],"offsets":[[0,9]],"normalized":[{"db_name":"MESH","db_id":"C047847"}]},{"id":"25173","type":"Chemical","text":["Flestolol"],"offsets":[[65,74]],"normalized":[{"db_name":"MESH","db_id":"C047847"}]},{"id":"25174","type":"Chemical","text":["ACC-9089"],"offsets":[[76,84]],"normalized":[{"db_name":"MESH","db_id":"C047847"}]},{"id":"25175","type":"Chemical","text":["Flestolol"],"offsets":[[217,226]],"normalized":[{"db_name":"MESH","db_id":"C047847"}]},{"id":"25176","type":"Chemical","text":["flestolol"],"offsets":[[446,455]],"normalized":[{"db_name":"MESH","db_id":"C047847"}]},{"id":"25177","type":"Chemical","text":["Flestolol"],"offsets":[[555,564]],"normalized":[{"db_name":"MESH","db_id":"C047847"}]},{"id":"25178","type":"Chemical","text":["flestolol"],"offsets":[[686,695]],"normalized":[{"db_name":"MESH","db_id":"C047847"}]},{"id":"25179","type":"Chemical","text":["Flestolol"],"offsets":[[726,735]],"normalized":[{"db_name":"MESH","db_id":"C047847"}]},{"id":"25180","type":"Chemical","text":["isoproterenol"],"offsets":[[777,790]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"25181","type":"Disease","text":["tachycardia"],"offsets":[[799,810]],"normalized":[{"db_name":"MESH","db_id":"D013610"}]},{"id":"25182","type":"Chemical","text":["flestolol"],"offsets":[[858,867]],"normalized":[{"db_name":"MESH","db_id":"C047847"}]},{"id":"25183","type":"Chemical","text":["flestolol"],"offsets":[[951,960]],"normalized":[{"db_name":"MESH","db_id":"C047847"}]},{"id":"25184","type":"Chemical","text":["Flestolol"],"offsets":[[1071,1080]],"normalized":[{"db_name":"MESH","db_id":"C047847"}]},{"id":"25185","type":"Disease","text":["supraventricular tachyarrhythmia"],"offsets":[[1129,1161]],"normalized":[{"db_name":"MESH","db_id":"D013617"}]},{"id":"25186","type":"Disease","text":["unstable angina"],"offsets":[[1180,1195]],"normalized":[{"db_name":"MESH","db_id":"D000789"}]},{"id":"25187","type":"Chemical","text":["flestolol"],"offsets":[[1197,1206]],"normalized":[{"db_name":"MESH","db_id":"C047847"}]},{"id":"25188","type":"Disease","text":["chest pain"],"offsets":[[1266,1276]],"normalized":[{"db_name":"MESH","db_id":"D002637"}]},{"id":"25189","type":"Chemical","text":["flestolol"],"offsets":[[1299,1308]],"normalized":[{"db_name":"MESH","db_id":"C047847"}]},{"id":"25190","type":"Chemical","text":["flestolol"],"offsets":[[1396,1405]],"normalized":[{"db_name":"MESH","db_id":"C047847"}]}],"events":[],"coreferences":[],"relations":[{"id":"25191","type":"CID","arg1_id":"25180","arg2_id":"25181","normalized":[]}]}
{"id":"25192","document_id":"1639466","passages":[{"id":"25193","type":"title","text":["Adverse effect of the calcium channel blocker nitrendipine on nephrosclerosis in rats with renovascular hypertension."],"offsets":[[0,117]]},{"id":"25194","type":"abstract","text":["The effect of a 6-week treatment with the calcium channel blocker nitrendipine or the angiotensin converting enzyme inhibitor enalapril on blood pressure, albuminuria, renal hemodynamics, and morphology of the nonclipped kidney was studied in rats with two-kidney, one clip renovascular hypertension. Six weeks after clipping of one renal artery, hypertensive rats (178 +\/- 4 mm Hg) were randomly assigned to three groups: untreated hypertensive controls (n = 8), enalapril-treated (n = 8), or nitrendipine-treated (n = 10). Sham-operated rats served as normotensive controls (128 +\/- 3 mm Hg, n = 8). After 6 weeks of treatment, renal hemodynamics (glomerular filtration rate and renal plasma flow) were measured in the anesthetized rats. Renal tissue was obtained for determination of glomerular size and sclerosis. Enalapril but not nitrendipine reduced blood pressure significantly. After 6 weeks of therapy, glomerular filtration rate was not different among the studied groups. Renal plasma flow increased, but albumin excretion and glomerulosclerosis did not change after enalapril treatment. In contrast, in the nitrendipine-treated group albuminuria increased from 12.8 +\/- 2 progressively to 163 +\/- 55 compared with 19.2 +\/- 9 mg\/24 hr in the hypertensive controls. Furthermore, glomerulosclerosis index was significantly increased in the nitrendipine-treated group compared with the hypertensive controls (0.38 +\/- 0.1 versus 0.13 +\/- 0.04). In addition, glomerular size was higher in the nitrendipine-treated group (14.9 +\/- 0.17 10(-3) mm2) but lower in the enalapril-treated group (11.5 +\/- 0.15 10(-3) mm2) compared with the hypertensive controls (12.1 +\/- 0.17 10(-3) mm2).(ABSTRACT TRUNCATED AT 250 WORDS)"],"offsets":[[118,1841]]}],"entities":[{"id":"25195","type":"Chemical","text":["calcium"],"offsets":[[22,29]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"25196","type":"Chemical","text":["nitrendipine"],"offsets":[[46,58]],"normalized":[{"db_name":"MESH","db_id":"D009568"}]},{"id":"25197","type":"Disease","text":["nephrosclerosis"],"offsets":[[62,77]],"normalized":[{"db_name":"MESH","db_id":"D009400"}]},{"id":"25198","type":"Disease","text":["renovascular 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{"id":"25243","document_id":"1527456","passages":[{"id":"25244","type":"title","text":["Treatment of tinnitus by intratympanic instillation of lignocaine (lidocaine) 2 per cent through ventilation tubes."],"offsets":[[0,115]]},{"id":"25245","type":"abstract","text":["Idiopathic subjective tinnitus (IST) is one of the most obscure otological pathologies. This paper presents the results of treating IST by intratympanic instillation of lignocaine (lidocaine) 2 per cent through a grommet, for five weekly courses. Fifty-two patients suffering from intractable tinnitus entered this therapeutic trial, but only nine finished all five courses. In one patient, the tinnitus was almost completely abolished, but in all the nine patients the decompensated tinnitus changed to a compensated one. We suggest this mode of treatment for patients that were previously treated by drugs, acupuncture and biofeedback, with disappointing results. Patients should be warned about the side effects of vertigo and vomiting, which subsides gradually with every new instillation, and that the tinnitus may not disappear but will be alleviated, enabling them to cope more easily with the disease and lead a more normal life."],"offsets":[[116,1053]]}],"entities":[{"id":"25246","type":"Disease","text":["tinnitus"],"offsets":[[13,21]],"normalized":[{"db_name":"MESH","db_id":"D014012"}]},{"id":"25247","type":"Chemical","text":["lignocaine"],"offsets":[[55,65]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"25248","type":"Chemical","text":["lidocaine"],"offsets":[[67,76]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"25249","type":"Disease","text":["Idiopathic subjective tinnitus"],"offsets":[[116,146]],"normalized":[{"db_name":"MESH","db_id":"D014012"}]},{"id":"25250","type":"Disease","text":["IST"],"offsets":[[148,151]],"normalized":[{"db_name":"MESH","db_id":"D014012"}]},{"id":"25251","type":"Disease","text":["IST"],"offsets":[[248,251]],"normalized":[{"db_name":"MESH","db_id":"D014012"}]},{"id":"25252","type":"Chemical","text":["lignocaine"],"offsets":[[285,295]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"25253","type":"Chemical","text":["lidocaine"],"offsets":[[297,306]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"25254","type":"Disease","text":["tinnitus"],"offsets":[[409,417]],"normalized":[{"db_name":"MESH","db_id":"D014012"}]},{"id":"25255","type":"Disease","text":["tinnitus"],"offsets":[[511,519]],"normalized":[{"db_name":"MESH","db_id":"D014012"}]},{"id":"25256","type":"Disease","text":["tinnitus"],"offsets":[[600,608]],"normalized":[{"db_name":"MESH","db_id":"D014012"}]},{"id":"25257","type":"Disease","text":["vertigo"],"offsets":[[834,841]],"normalized":[{"db_name":"MESH","db_id":"D014717"}]},{"id":"25258","type":"Disease","text":["vomiting"],"offsets":[[846,854]],"normalized":[{"db_name":"MESH","db_id":"D014839"}]},{"id":"25259","type":"Disease","text":["tinnitus"],"offsets":[[923,931]],"normalized":[{"db_name":"MESH","db_id":"D014012"}]}],"events":[],"coreferences":[],"relations":[{"id":"25260","type":"CID","arg1_id":"25247","arg2_id":"25257","normalized":[]},{"id":"25261","type":"CID","arg1_id":"25248","arg2_id":"25257","normalized":[]},{"id":"25262","type":"CID","arg1_id":"25252","arg2_id":"25257","normalized":[]},{"id":"25263","type":"CID","arg1_id":"25253","arg2_id":"25257","normalized":[]},{"id":"25264","type":"CID","arg1_id":"25247","arg2_id":"25258","normalized":[]},{"id":"25265","type":"CID","arg1_id":"25248","arg2_id":"25258","normalized":[]},{"id":"25266","type":"CID","arg1_id":"25252","arg2_id":"25258","normalized":[]},{"id":"25267","type":"CID","arg1_id":"25253","arg2_id":"25258","normalized":[]}]}
{"id":"25268","document_id":"220563","passages":[{"id":"25269","type":"title","text":["Perhexiline maleate and peripheral neuropathy."],"offsets":[[0,46]]},{"id":"25270","type":"abstract","text":["Peripheral neuropathy has been noted as a complication of therapy with perhexiline maleate, a drug widely used in France (and in clinical trials in the United States) for the prophylactic treatment of angina pectoris. In 24 patients with this complication, the marked slowing of motor nerve conduction velocity and the electromyographic changes imply mainly a demyelinating disorder. Improvement was noted with cessation of therapy. In a few cases the presence of active denervation signified a poor prognosis, with only slight improvement. The underlying mechanism causing the neuropathy is not yet fully known, although some evidence indicates that it may be a lipid storage process."],"offsets":[[47,732]]}],"entities":[{"id":"25271","type":"Chemical","text":["Perhexiline maleate"],"offsets":[[0,19]],"normalized":[{"db_name":"MESH","db_id":"C023470"}]},{"id":"25272","type":"Disease","text":["peripheral neuropathy"],"offsets":[[24,45]],"normalized":[{"db_name":"MESH","db_id":"D010523"}]},{"id":"25273","type":"Disease","text":["Peripheral neuropathy"],"offsets":[[47,68]],"normalized":[{"db_name":"MESH","db_id":"D010523"}]},{"id":"25274","type":"Chemical","text":["perhexiline maleate"],"offsets":[[118,137]],"normalized":[{"db_name":"MESH","db_id":"C023470"}]},{"id":"25275","type":"Disease","text":["angina pectoris"],"offsets":[[248,263]],"normalized":[{"db_name":"MESH","db_id":"D000787"}]},{"id":"25276","type":"Disease","text":["demyelinating disorder"],"offsets":[[407,429]],"normalized":[{"db_name":"MESH","db_id":"D003711"}]},{"id":"25277","type":"Disease","text":["neuropathy"],"offsets":[[625,635]],"normalized":[{"db_name":"MESH","db_id":"D009422"}]}],"events":[],"coreferences":[],"relations":[{"id":"25278","type":"CID","arg1_id":"25271","arg2_id":"25276","normalized":[]},{"id":"25279","type":"CID","arg1_id":"25274","arg2_id":"25276","normalized":[]},{"id":"25280","type":"CID","arg1_id":"25271","arg2_id":"25272","normalized":[]},{"id":"25281","type":"CID","arg1_id":"25271","arg2_id":"25273","normalized":[]},{"id":"25282","type":"CID","arg1_id":"25274","arg2_id":"25272","normalized":[]},{"id":"25283","type":"CID","arg1_id":"25274","arg2_id":"25273","normalized":[]}]}
{"id":"25284","document_id":"137340","passages":[{"id":"25285","type":"title","text":["Effect of humoral modulators of morphine-induced increase in locomotor activity of mice."],"offsets":[[0,88]]},{"id":"25286","type":"abstract","text":["The effect of humoral modulators on the morphine-induced increase in locomotor activity of mice was studied. The subcutaneous administration of 10 mg\/kg of morphine-HC1 produced a marked increase in locomotor activity in mice. The morphine-induced hyperactivity was potentiated by scopolamine and attenuated by physostigmine. In contrast, both methscopolamine and neostigmine, which do not penetrate the blood-brain barrier, had no effect on the hyperactivity produced by morphine. Pretreatment of mice with alpha-methyltyrosine (20 mg\/kg i.p., one hour), an inhibitor of tyrosine hydroxylase, significantly decreased the activity-increasing effects of morphine. On the other hand, pretreatment with p-chlorophenylalamine (3 X 320 mg\/kg i.p., 24 hr), a serotonin depletor, caused no significant change in the hyperactivity. The study suggests that the activity-increasing effects of morphine are mediated by the release of catecholamines from adrenergic neurons in the brain. And the results are consistent with the hypothesis that morphine acts by retarding the release of acetylcholine at some central cholinergic synapses. It is also suggested from collected evidence that the activity-increasing effects of morphine in mice are mediated by mechanisms different from those which mediate the activity-increasing effects of morphine in rats."],"offsets":[[89,1431]]}],"entities":[{"id":"25287","type":"Chemical","text":["morphine"],"offsets":[[32,40]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"25288","type":"Disease","text":["increase in locomotor activity"],"offsets":[[49,79]],"normalized":[{"db_name":"MESH","db_id":"D006948"}]},{"id":"25289","type":"Chemical","text":["morphine"],"offsets":[[129,137]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"25290","type":"Disease","text":["increase in locomotor activity"],"offsets":[[146,176]],"normalized":[{"db_name":"MESH","db_id":"D006948"}]},{"id":"25291","type":"Chemical","text":["morphine"],"offsets":[[245,253]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"25292","type":"Disease","text":["increase in locomotor 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{"id":"25379","document_id":"9931093","passages":[{"id":"25380","type":"title","text":["Mechanisms of FK 506-induced hypertension in the rat."],"offsets":[[0,53]]},{"id":"25381","type":"abstract","text":["-Tacrolimus (FK 506) is a powerful, widely used immunosuppressant. The clinical utility of FK 506 is complicated by substantial hypertension and nephrotoxicity. To clarify the mechanisms of FK 506-induced hypertension, we studied the chronic effects of FK 506 on the synthesis of endothelin-1 (ET-1), the expression of mRNA of ET-1 and endothelin-converting enzyme-1 (ECE-1), the endothelial nitric oxide synthase (eNOS) activity, and the expression of mRNA of eNOS and C-type natriuretic peptide (CNP) in rat blood vessels. In addition, the effect of the specific endothelin type A receptor antagonist FR 139317 on FK 506-induced hypertension in rats was studied. FK 506, 5 mg. kg-1. d-1 given for 4 weeks, elevated blood pressure from 102+\/-13 to 152+\/-15 mm Hg and increased the synthesis of ET-1 and the levels of ET-1 mRNA in the mesenteric artery (240% and 230%, respectively). Little change was observed in the expression of ECE-1 mRNA and CNP mRNA. FK 506 decreased eNOS activity and the levels of eNOS mRNA in the aorta (48% and 55%, respectively). The administration of FR 139317 (10 mg. kg-1. d-1) prevented FK 506-induced hypertension in rats. These results indicate that FK 506 may increase blood pressure not only by increasing ET-1 production but also by decreasing NO synthesis in the vasculature."],"offsets":[[54,1367]]}],"entities":[{"id":"25382","type":"Chemical","text":["FK 506"],"offsets":[[14,20]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"25383","type":"Disease","text":["hypertension"],"offsets":[[29,41]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"25384","type":"Chemical","text":["Tacrolimus"],"offsets":[[55,65]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"25385","type":"Chemical","text":["FK 506"],"offsets":[[67,73]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"25386","type":"Chemical","text":["FK 506"],"offsets":[[145,151]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"25387","type":"Disease","text":["hypertension"],"offsets":[[182,194]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"25388","type":"Disease","text":["nephrotoxicity"],"offsets":[[199,213]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"25389","type":"Chemical","text":["FK 506"],"offsets":[[244,250]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"25390","type":"Disease","text":["hypertension"],"offsets":[[259,271]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"25391","type":"Chemical","text":["FK 506"],"offsets":[[307,313]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"25392","type":"Chemical","text":["nitric oxide"],"offsets":[[446,458]],"normalized":[{"db_name":"MESH","db_id":"D009569"}]},{"id":"25393","type":"Chemical","text":["FR 139317"],"offsets":[[657,666]],"normalized":[{"db_name":"MESH","db_id":"C079574"}]},{"id":"25394","type":"Chemical","text":["FK 506"],"offsets":[[670,676]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"25395","type":"Disease","text":["hypertension"],"offsets":[[685,697]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"25396","type":"Chemical","text":["FK 506"],"offsets":[[719,725]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"25397","type":"Chemical","text":["FK 506"],"offsets":[[1011,1017]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"25398","type":"Chemical","text":["FR 139317"],"offsets":[[1134,1143]],"normalized":[{"db_name":"MESH","db_id":"C079574"}]},{"id":"25399","type":"Chemical","text":["FK 506"],"offsets":[[1173,1179]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"25400","type":"Disease","text":["hypertension"],"offsets":[[1188,1200]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"25401","type":"Chemical","text":["FK 506"],"offsets":[[1238,1244]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"25402","type":"Chemical","text":["NO"],"offsets":[[1335,1337]],"normalized":[{"db_name":"MESH","db_id":"D009569"}]}],"events":[],"coreferences":[],"relations":[{"id":"25403","type":"CID","arg1_id":"25382","arg2_id":"25383","normalized":[]},{"id":"25404","type":"CID","arg1_id":"25382","arg2_id":"25387","normalized":[]},{"id":"25405","type":"CID","arg1_id":"25382","arg2_id":"25390","normalized":[]},{"id":"25406","type":"CID","arg1_id":"25382","arg2_id":"25395","normalized":[]},{"id":"25407","type":"CID","arg1_id":"25382","arg2_id":"25400","normalized":[]},{"id":"25408","type":"CID","arg1_id":"25384","arg2_id":"25383","normalized":[]},{"id":"25409","type":"CID","arg1_id":"25384","arg2_id":"25387","normalized":[]},{"id":"25410","type":"CID","arg1_id":"25384","arg2_id":"25390","normalized":[]},{"id":"25411","type":"CID","arg1_id":"25384","arg2_id":"25395","normalized":[]},{"id":"25412","type":"CID","arg1_id":"25384","arg2_id":"25400","normalized":[]},{"id":"25413","type":"CID","arg1_id":"25385","arg2_id":"25383","normalized":[]},{"id":"25414","type":"CID","arg1_id":"25385","arg2_id":"25387","normalized":[]},{"id":"25415","type":"CID","arg1_id":"25385","arg2_id":"25390","normalized":[]},{"id":"25416","type":"CID","arg1_id":"25385","arg2_id":"25395","normalized":[]},{"id":"25417","type":"CID","arg1_id":"25385","arg2_id":"25400","normalized":[]},{"id":"25418","type":"CID","arg1_id":"25386","arg2_id":"25383","normalized":[]},{"id":"25419","type":"CID","arg1_id":"25386","arg2_id":"25387","normalized":[]},{"id":"25420","type":"CID","arg1_id":"25386","arg2_id":"25390","normalized":[]},{"id":"25421","type":"CID","arg1_id":"25386","arg2_id":"25395","normalized":[]},{"id":"25422","type":"CID","arg1_id":"25386","arg2_id":"25400","normalized":[]},{"id":"25423","type":"CID","arg1_id":"25389","arg2_id":"25383","normalized":[]},{"id":"25424","type":"CID","arg1_id":"25389","arg2_id":"25387","normalized":[]},{"id":"25425","type":"CID","arg1_id":"25389","arg2_id":"25390","normalized":[]},{"id":"25426","type":"CID","arg1_id":"25389","arg2_id":"25395","normalized":[]},{"id":"25427","type":"CID","arg1_id":"25389","arg2_id":"25400","normalized":[]},{"id":"25428","type":"CID","arg1_id":"25391","arg2_id":"25383","normalized":[]},{"id":"25429","type":"CID","arg1_id":"25391","arg2_id":"25387","normalized":[]},{"id":"25430","type":"CID","arg1_id":"25391","arg2_id":"25390","normalized":[]},{"id":"25431","type":"CID","arg1_id":"25391","arg2_id":"25395","normalized":[]},{"id":"25432","type":"CID","arg1_id":"25391","arg2_id":"25400","normalized":[]},{"id":"25433","type":"CID","arg1_id":"25394","arg2_id":"25383","normalized":[]},{"id":"25434","type":"CID","arg1_id":"25394","arg2_id":"25387","normalized":[]},{"id":"25435","type":"CID","arg1_id":"25394","arg2_id":"25390","normalized":[]},{"id":"25436","type":"CID","arg1_id":"25394","arg2_id":"25395","normalized":[]},{"id":"25437","type":"CID","arg1_id":"25394","arg2_id":"25400","normalized":[]},{"id":"25438","type":"CID","arg1_id":"25396","arg2_id":"25383","normalized":[]},{"id":"25439","type":"CID","arg1_id":"25396","arg2_id":"25387","normalized":[]},{"id":"25440","type":"CID","arg1_id":"25396","arg2_id":"25390","normalized":[]},{"id":"25441","type":"CID","arg1_id":"25396","arg2_id":"25395","normalized":[]},{"id":"25442","type":"CID","arg1_id":"25396","arg2_id":"25400","normalized":[]},{"id":"25443","type":"CID","arg1_id":"25397","arg2_id":"25383","normalized":[]},{"id":"25444","type":"CID","arg1_id":"25397","arg2_id":"25387","normalized":[]},{"id":"25445","type":"CID","arg1_id":"25397","arg2_id":"25390","normalized":[]},{"id":"25446","type":"CID","arg1_id":"25397","arg2_id":"25395","normalized":[]},{"id":"25447","type":"CID","arg1_id":"25397","arg2_id":"25400","normalized":[]},{"id":"25448","type":"CID","arg1_id":"25399","arg2_id":"25383","normalized":[]},{"id":"25449","type":"CID","arg1_id":"25399","arg2_id":"25387","normalized":[]},{"id":"25450","type":"CID","arg1_id":"25399","arg2_id":"25390","normalized":[]},{"id":"25451","type":"CID","arg1_id":"25399","arg2_id":"25395","normalized":[]},{"id":"25452","type":"CID","arg1_id":"25399","arg2_id":"25400","normalized":[]},{"id":"25453","type":"CID","arg1_id":"25401","arg2_id":"25383","normalized":[]},{"id":"25454","type":"CID","arg1_id":"25401","arg2_id":"25387","normalized":[]},{"id":"25455","type":"CID","arg1_id":"25401","arg2_id":"25390","normalized":[]},{"id":"25456","type":"CID","arg1_id":"25401","arg2_id":"25395","normalized":[]},{"id":"25457","type":"CID","arg1_id":"25401","arg2_id":"25400","normalized":[]}]}
{"id":"25458","document_id":"20633755","passages":[{"id":"25459","type":"title","text":["Suxamethonium induced prolonged apnea in a patient receiving electroconvulsive therapy."],"offsets":[[0,87]]},{"id":"25460","type":"abstract","text":["Suxamethonium causes prolonged apnea in patients in whom pseudocholinesterase enzyme gets deactivated by organophosphorus (OP) poisons. Here, we present a similar incident in a severely depressed patient who received electroconvulsive therapy (ECT). Prolonged apnea in our case ensued because the information about suicidal attempt by OP compound was concealed from the treating team."],"offsets":[[88,472]]}],"entities":[{"id":"25461","type":"Chemical","text":["Suxamethonium"],"offsets":[[0,13]],"normalized":[{"db_name":"MESH","db_id":"D013390"}]},{"id":"25462","type":"Disease","text":["apnea"],"offsets":[[32,37]],"normalized":[{"db_name":"MESH","db_id":"D001049"}]},{"id":"25463","type":"Chemical","text":["Suxamethonium"],"offsets":[[88,101]],"normalized":[{"db_name":"MESH","db_id":"D013390"}]},{"id":"25464","type":"Disease","text":["apnea"],"offsets":[[119,124]],"normalized":[{"db_name":"MESH","db_id":"D001049"}]},{"id":"25465","type":"Chemical","text":["organophosphorus (OP) poisons"],"offsets":[[193,222]],"normalized":[{"db_name":"MESH","db_id":"D009943"}]},{"id":"25466","type":"Disease","text":["depressed"],"offsets":[[274,283]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"25467","type":"Disease","text":["apnea"],"offsets":[[348,353]],"normalized":[{"db_name":"MESH","db_id":"D001049"}]},{"id":"25468","type":"Chemical","text":["OP compound"],"offsets":[[423,434]],"normalized":[{"db_name":"MESH","db_id":"D009943"}]}],"events":[],"coreferences":[],"relations":[{"id":"25469","type":"CID","arg1_id":"25465","arg2_id":"25462","normalized":[]},{"id":"25470","type":"CID","arg1_id":"25465","arg2_id":"25464","normalized":[]},{"id":"25471","type":"CID","arg1_id":"25465","arg2_id":"25467","normalized":[]},{"id":"25472","type":"CID","arg1_id":"25468","arg2_id":"25462","normalized":[]},{"id":"25473","type":"CID","arg1_id":"25468","arg2_id":"25464","normalized":[]},{"id":"25474","type":"CID","arg1_id":"25468","arg2_id":"25467","normalized":[]},{"id":"25475","type":"CID","arg1_id":"25461","arg2_id":"25462","normalized":[]},{"id":"25476","type":"CID","arg1_id":"25461","arg2_id":"25464","normalized":[]},{"id":"25477","type":"CID","arg1_id":"25461","arg2_id":"25467","normalized":[]},{"id":"25478","type":"CID","arg1_id":"25463","arg2_id":"25462","normalized":[]},{"id":"25479","type":"CID","arg1_id":"25463","arg2_id":"25464","normalized":[]},{"id":"25480","type":"CID","arg1_id":"25463","arg2_id":"25467","normalized":[]}]}
{"id":"25481","document_id":"20067456","passages":[{"id":"25482","type":"title","text":["The effects of the adjunctive bupropion on male sexual dysfunction induced by a selective serotonin reuptake inhibitor: a double-blind placebo-controlled and randomized study."],"offsets":[[0,175]]},{"id":"25483","type":"abstract","text":["OBJECTIVE: To determine the safety and efficacy of adjunctive bupropion sustained-release (SR) on male sexual dysfunction (SD) induced by a selective serotonin reuptake inhibitor (SSRI), as SD is a common side-effect of SSRIs and the most effective treatments have yet to be determined. PATIENTS AND METHODS: The randomized sample consisted of 234 euthymic men who were receiving some type of SSRI. The men were randomly assigned to bupropion SR (150 mg twice daily, 117) or placebo (twice daily, 117) for 12 weeks. Efficacy was evaluated using the Clinical Global Impression-Sexual Function (CGI-SF; the primary outcome measure), the International Index of Erectile Function (IIEF), Arizona Sexual Experience Scale (ASEX), and Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) (secondary outcome measures). Participants were followed biweekly during study period. RESULTS: After 12 weeks of treatment, the mean (sd) scores for CGI-SF were significantly lower, i.e. better, in patients on bupropion SR, at 2.4 (1.2), than in the placebo group, at 3.9 (1.1) (P= 0.01). Men who received bupropion had a significant increase in the total IIEF score (54.4% vs 1.2%; P= 0.003), and in the five different domains of the IIEF. Total ASEX scores were significantly lower, i.e. better, among men who received bupropion than placebo, at 15.5 (4.3) vs 21.5 (4.7) (P= 0.002). The EDITS scores were 67.4 (10.2) for the bupropion and 36.3 (11.7) for the placebo group (P= 0.001). The ASEX score and CGI-SF score were correlated (P= 0.003). In linear regression analyses the CGI-SF score was not affected significantly by the duration of SD, type of SSRI used and age. CONCLUSIONS: Bupropion is an effective treatment for male SD induced by SSRIs. These results provide empirical support for conducting a further study of bupropion."],"offsets":[[176,2008]]}],"entities":[{"id":"25484","type":"Chemical","text":["bupropion"],"offsets":[[30,39]],"normalized":[{"db_name":"MESH","db_id":"D016642"}]},{"id":"25485","type":"Disease","text":["sexual dysfunction"],"offsets":[[48,66]],"normalized":[{"db_name":"MESH","db_id":"D012735"}]},{"id":"25486","type":"Chemical","text":["selective serotonin reuptake inhibitor"],"offsets":[[80,118]],"normalized":[{"db_name":"MESH","db_id":"D017367"}]},{"id":"25487","type":"Chemical","text":["bupropion"],"offsets":[[238,247]],"normalized":[{"db_name":"MESH","db_id":"D016642"}]},{"id":"25488","type":"Disease","text":["sexual dysfunction"],"offsets":[[279,297]],"normalized":[{"db_name":"MESH","db_id":"D012735"}]},{"id":"25489","type":"Disease","text":["SD"],"offsets":[[299,301]],"normalized":[{"db_name":"MESH","db_id":"D012735"}]},{"id":"25490","type":"Chemical","text":["selective serotonin reuptake inhibitor"],"offsets":[[316,354]],"normalized":[{"db_name":"MESH","db_id":"D017367"}]},{"id":"25491","type":"Chemical","text":["SSRI"],"offsets":[[356,360]],"normalized":[{"db_name":"MESH","db_id":"D017367"}]},{"id":"25492","type":"Disease","text":["SD"],"offsets":[[366,368]],"normalized":[{"db_name":"MESH","db_id":"D012735"}]},{"id":"25493","type":"Chemical","text":["SSRIs"],"offsets":[[396,401]],"normalized":[{"db_name":"MESH","db_id":"D017367"}]},{"id":"25494","type":"Chemical","text":["SSRI"],"offsets":[[569,573]],"normalized":[{"db_name":"MESH","db_id":"D017367"}]},{"id":"25495","type":"Chemical","text":["bupropion"],"offsets":[[609,618]],"normalized":[{"db_name":"MESH","db_id":"D016642"}]},{"id":"25496","type":"Disease","text":["Erectile Dysfunction"],"offsets":[[904,924]],"normalized":[{"db_name":"MESH","db_id":"D007172"}]},{"id":"25497","type":"Chemical","text":["bupropion"],"offsets":[[1180,1189]],"normalized":[{"db_name":"MESH","db_id":"D016642"}]},{"id":"25498","type":"Chemical","text":["bupropion"],"offsets":[[1276,1285]],"normalized":[{"db_name":"MESH","db_id":"D016642"}]},{"id":"25499","type":"Chemical","text":["bupropion"],"offsets":[[1491,1500]],"normalized":[{"db_name":"MESH","db_id":"D016642"}]},{"id":"25500","type":"Chemical","text":["bupropion"],"offsets":[[1597,1606]],"normalized":[{"db_name":"MESH","db_id":"D016642"}]},{"id":"25501","type":"Disease","text":["SD"],"offsets":[[1814,1816]],"normalized":[{"db_name":"MESH","db_id":"D012735"}]},{"id":"25502","type":"Chemical","text":["SSRI"],"offsets":[[1826,1830]],"normalized":[{"db_name":"MESH","db_id":"D017367"}]},{"id":"25503","type":"Chemical","text":["Bupropion"],"offsets":[[1858,1867]],"normalized":[{"db_name":"MESH","db_id":"D016642"}]},{"id":"25504","type":"Disease","text":["SD"],"offsets":[[1903,1905]],"normalized":[{"db_name":"MESH","db_id":"D012735"}]},{"id":"25505","type":"Chemical","text":["SSRIs"],"offsets":[[1917,1922]],"normalized":[{"db_name":"MESH","db_id":"D017367"}]},{"id":"25506","type":"Chemical","text":["bupropion"],"offsets":[[1998,2007]],"normalized":[{"db_name":"MESH","db_id":"D016642"}]}],"events":[],"coreferences":[],"relations":[{"id":"25507","type":"CID","arg1_id":"25486","arg2_id":"25496","normalized":[]},{"id":"25508","type":"CID","arg1_id":"25490","arg2_id":"25496","normalized":[]},{"id":"25509","type":"CID","arg1_id":"25491","arg2_id":"25496","normalized":[]},{"id":"25510","type":"CID","arg1_id":"25493","arg2_id":"25496","normalized":[]},{"id":"25511","type":"CID","arg1_id":"25494","arg2_id":"25496","normalized":[]},{"id":"25512","type":"CID","arg1_id":"25502","arg2_id":"25496","normalized":[]},{"id":"25513","type":"CID","arg1_id":"25505","arg2_id":"25496","normalized":[]}]}
{"id":"25514","document_id":"18464113","passages":[{"id":"25515","type":"title","text":["Lamivudine for the prevention of hepatitis B virus reactivation in hepatitis-B surface antigen (HBSAG) seropositive cancer patients undergoing cytotoxic chemotherapy."],"offsets":[[0,166]]},{"id":"25516","type":"abstract","text":["Hepatitis B virus (HBV) is one of the major causes of chronic liver disease worldwide. Cancer patients who are chronic carriers of HBV have a higher hepatic complication rate while receiving cytotoxic chemotherapy (CT) and this has mainly been attributed to HBV reactivation. In this study, cancer patients who have solid and hematological malignancies with chronic HBV infection received the antiviral agent lamivudine prior and during CT compared with historical control group who did not receive lamivudine. The objectives were to assess the efficacy of lamivudine in reducing the incidence of HBV reactivation, and diminishing morbidity and mortality during CT. Two groups were compared in this study. The prophylactic lamivudin group consisted of 37 patients who received prophylactic lamivudine treatment. The historical controls consisted of 50 consecutive patients who underwent CT without prophylactic lamivudine. They were followed up during and for 8 weeks after CT. The outcomes were compared for both groups. Of our control group (n= 50), 21 patients (42%) were established hepatitis. Twelve (24%) of them were evaluated as severe hepatitis. In the prophylactic lamivudine group severe hepatitis were observed only in 1 patient (2.7%) of 37 patients (p < 0.006). Comparison of the mean ALT values revealed significantly higher mean alanine aminotransferase (ALT) values in the control group than the prophylactic lamivudine group; 154:64 (p < 0.32). Our study suggests that prophylactic lamivudine significantly decreases the incidence of HBV reactivation and overall morbidity in cancer patients during and after immunosuppressive therapy. Further studies are needed to determine the most appropriate nucleoside or nucleotide analogue for antiviral prophylaxis during CT and the optimal duration of administration after completion of CT."],"offsets":[[167,2018]]}],"entities":[{"id":"25517","type":"Chemical","text":["Lamivudine"],"offsets":[[0,10]],"normalized":[{"db_name":"MESH","db_id":"D019259"}]},{"id":"25518","type":"Disease","text":["hepatitis B"],"offsets":[[33,44]],"normalized":[{"db_name":"MESH","db_id":"D006509"}]},{"id":"25519","type":"Chemical","text":["hepatitis-B surface antigen"],"offsets":[[67,94]],"normalized":[{"db_name":"MESH","db_id":"D006514"}]},{"id":"25520","type":"Chemical","text":["HBSAG"],"offsets":[[96,101]],"normalized":[{"db_name":"MESH","db_id":"D006514"}]},{"id":"25521","type":"Disease","text":["cancer"],"offsets":[[116,122]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"25522","type":"Disease","text":["Hepatitis B"],"offsets":[[167,178]],"normalized":[{"db_name":"MESH","db_id":"D006509"}]},{"id":"25523","type":"Disease","text":["liver disease"],"offsets":[[229,242]],"normalized":[{"db_name":"MESH","db_id":"D008107"}]},{"id":"25524","type":"Disease","text":["Cancer"],"offsets":[[254,260]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"25525","type":"Disease","text":["hepatic complication"],"offsets":[[316,336]],"normalized":[{"db_name":"MESH","db_id":"D008107"}]},{"id":"25526","type":"Disease","text":["cancer"],"offsets":[[458,464]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"25527","type":"Disease","text":["hematological malignancies"],"offsets":[[493,519]],"normalized":[{"db_name":"MESH","db_id":"D019337"}]},{"id":"25528","type":"Disease","text":["HBV infection"],"offsets":[[533,546]],"normalized":[{"db_name":"MESH","db_id":"D006509"}]},{"id":"25529","type":"Chemical","text":["lamivudine"],"offsets":[[576,586]],"normalized":[{"db_name":"MESH","db_id":"D019259"}]},{"id":"25530","type":"Chemical","text":["lamivudine"],"offsets":[[666,676]],"normalized":[{"db_name":"MESH","db_id":"D019259"}]},{"id":"25531","type":"Chemical","text":["lamivudine"],"offsets":[[724,734]],"normalized":[{"db_name":"MESH","db_id":"D019259"}]},{"id":"25532","type":"Chemical","text":["lamivudin"],"offsets":[[890,899]],"normalized":[{"db_name":"MESH","db_id":"D019259"}]},{"id":"25533","type":"Chemical","text":["lamivudine"],"offsets":[[957,967]],"normalized":[{"db_name":"MESH","db_id":"D019259"}]},{"id":"25534","type":"Chemical","text":["lamivudine"],"offsets":[[1078,1088]],"normalized":[{"db_name":"MESH","db_id":"D019259"}]},{"id":"25535","type":"Disease","text":["hepatitis"],"offsets":[[1254,1263]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"25536","type":"Disease","text":["hepatitis"],"offsets":[[1311,1320]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"25537","type":"Chemical","text":["lamivudine"],"offsets":[[1342,1352]],"normalized":[{"db_name":"MESH","db_id":"D019259"}]},{"id":"25538","type":"Disease","text":["hepatitis"],"offsets":[[1366,1375]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"25539","type":"Chemical","text":["alanine"],"offsets":[[1512,1519]],"normalized":[{"db_name":"MESH","db_id":"D000409"}]},{"id":"25540","type":"Chemical","text":["lamivudine"],"offsets":[[1593,1603]],"normalized":[{"db_name":"MESH","db_id":"D019259"}]},{"id":"25541","type":"Chemical","text":["lamivudine"],"offsets":[[1667,1677]],"normalized":[{"db_name":"MESH","db_id":"D019259"}]},{"id":"25542","type":"Disease","text":["cancer"],"offsets":[[1761,1767]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"25543","type":"Chemical","text":["nucleoside"],"offsets":[[1882,1892]],"normalized":[{"db_name":"MESH","db_id":"D009705"}]},{"id":"25544","type":"Chemical","text":["nucleotide"],"offsets":[[1896,1906]],"normalized":[{"db_name":"MESH","db_id":"D009711"}]}],"events":[],"coreferences":[],"relations":[{"id":"25545","type":"CID","arg1_id":"25519","arg2_id":"25518","normalized":[]},{"id":"25546","type":"CID","arg1_id":"25519","arg2_id":"25522","normalized":[]},{"id":"25547","type":"CID","arg1_id":"25519","arg2_id":"25528","normalized":[]},{"id":"25548","type":"CID","arg1_id":"25520","arg2_id":"25518","normalized":[]},{"id":"25549","type":"CID","arg1_id":"25520","arg2_id":"25522","normalized":[]},{"id":"25550","type":"CID","arg1_id":"25520","arg2_id":"25528","normalized":[]}]}
{"id":"25551","document_id":"18308784","passages":[{"id":"25552","type":"title","text":["Ginsenoside Rg1 restores the impairment of learning induced by chronic morphine administration in rats."],"offsets":[[0,103]]},{"id":"25553","type":"abstract","text":["Rg1, as a ginsenoside extracted from Panax ginseng, could ameliorate spatial learning impairment. Previous studies have demonstrated that Rg1 might be a useful agent for the prevention and treatment of the adverse effects of morphine. The aim of this study was to investigate the effect of Rg1 on learning impairment by chronic morphine administration and the mechanism responsible for this effect. Male rats were subcutaneously injected with morphine (10 mg\/kg) twice a day at 12 hour intervals for 10 days, and Rg1 (30 mg\/kg) was intraperitoneally injected 2 hours after the second injection of morphine once a day for 10 days. Spatial learning capacity was assessed in the Morris water maze. The results showed that rats treated with Morphine\/Rg1 decreased escape latency and increased the time spent in platform quadrant and entering frequency. By implantation of electrodes and electrophysiological recording in vivo, the results showed that Rg1 restored the long-term potentiation (LTP) impaired by morphine in both freely moving and anaesthetised rats. The electrophysiological recording in vitro showed that Rg1 restored the LTP in slices from the rats treated with morphine, but not changed LTP in the slices from normal saline- or morphine\/Rg1-treated rats; this restoration could be inhibited by N-methyl-D-aspartate (NMDA) receptor antagonist MK801. We conclude that Rg1 may significantly improve the spatial learning capacity impaired by chonic morphine administration and restore the morphine-inhibited LTP. This effect is NMDA receptor dependent."],"offsets":[[104,1665]]}],"entities":[{"id":"25554","type":"Chemical","text":["Ginsenoside Rg1"],"offsets":[[0,15]],"normalized":[{"db_name":"MESH","db_id":"C035054"}]},{"id":"25555","type":"Disease","text":["impairment of learning"],"offsets":[[29,51]],"normalized":[{"db_name":"MESH","db_id":"D007859"}]},{"id":"25556","type":"Chemical","text":["morphine"],"offsets":[[71,79]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"25557","type":"Chemical","text":["Rg1"],"offsets":[[104,107]],"normalized":[{"db_name":"MESH","db_id":"C035054"}]},{"id":"25558","type":"Chemical","text":["ginsenoside"],"offsets":[[114,125]],"normalized":[{"db_name":"MESH","db_id":"D036145"}]},{"id":"25559","type":"Disease","text":["learning 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{"id":"25616","document_id":"17931375","passages":[{"id":"25617","type":"title","text":["A study on the effect of the duration of subcutaneous heparin injection on bruising and pain."],"offsets":[[0,93]]},{"id":"25618","type":"abstract","text":["AIM: This study was carried out to determine the effect of injection duration on bruising and pain following the administration of the subcutaneous injection of heparin. BACKGROUND: Although different methods to prevent bruising and pain following the subcutaneous injection of heparin have been widely studied and described, the effect of injection duration on the occurrence of bruising and pain is little documented. DESIGN: This study was designed as within-subject, quasi-experimental research. METHOD: The sample for the study consisted of 50 patients to whom subcutaneous heparin was administered. Heparin was injected over 10 seconds on the right abdominal site and 30 seconds on the left abdominal site. Injections areas were assessed for the presence of bruising at 48 and 72 hours after each injection. Dimensions of the bruising on the heparin applied areas were measured using transparent millimetric measuring paper. The visual analog scale (VAS) was used to measure pain intensity and a stop-watch was used to time the pain period. Data were analysed using chi-square test, Mann-Whitney U, Wilcoxon signed ranks tests and correlation. RESULTS: The percentage of bruising occurrence was 64% with the injection of 10 seconds duration and 42% in the 30-second injection. It was determined that the size of the bruising was smaller in the 30-second injection. Pain intensity and pain period were statistically significantly lower for the 30-second injection than for the 10-second injection. CONCLUSIONS: It was determined that injection duration had an effect on bruising and pain following the subcutaneous administration of heparin. This study should be repeated on a larger sample. RELEVANCE TO CLINICAL PRACTICE: When administering subcutaneous heparin injections, it is important to extend the duration of the 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Haloperidol administration (one dose of 12 mg\/kg once a week s.c.) for 4 weeks caused an increase in vacuous chewing, tongue protrusion and duration of facial twitching observed in four weekly evaluations. After the treatments and behavioral observation, glutamate uptake by segments of the brain was analyzed. A decreased glutamate uptake was observed in the subcortical parts of animals treated with reserpine and haloperidol, compared to the control. Importantly, a decrease in glutamate uptake correlates negatively with an increase in the incidence of orofacial diskinesia. These results indicate that early changes in glutamate transport may be related to the development of vacuous chewing movements in rats."],"offsets":[[138,1385]]}],"entities":[{"id":"25792","type":"Chemical","text":["reserpine"],"offsets":[[6,15]],"normalized":[{"db_name":"MESH","db_id":"D012110"}]},{"id":"25793","type":"Chemical","text":["haloperidol"],"offsets":[[31,42]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"25794","type":"Chemical","text":["glutamate"],"offsets":[[80,89]],"normalized":[{"db_name":"MESH","db_id":"D018698"}]},{"id":"25795","type":"Disease","text":["orofacial dyskinesia"],"offsets":[[108,128]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"25796","type":"Chemical","text":["Reserpine"],"offsets":[[138,147]],"normalized":[{"db_name":"MESH","db_id":"D012110"}]},{"id":"25797","type":"Chemical","text":["haloperidol"],"offsets":[[153,164]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"25798","type":"Disease","text":["orofacial 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{"id":"25873","document_id":"14698717","passages":[{"id":"25874","type":"title","text":["Acute psychosis due to treatment with phenytoin in a nonepileptic patient."],"offsets":[[0,74]]},{"id":"25875","type":"abstract","text":["The development of psychosis related to antiepileptic drug treatment is usually attributed to the interaction between the epileptic brain substratum and the antiepileptic drugs. The case of a nonepileptic patient who developed psychosis following phenytoin treatment for trigeminal neuralgia is described. This case suggests that the psychotic symptoms that occur following phenytoin treatment in some epileptic patients may be the direct result of medication, unrelated to seizures."],"offsets":[[75,558]]}],"entities":[{"id":"25876","type":"Disease","text":["Acute psychosis"],"offsets":[[0,15]],"normalized":[{"db_name":"MESH","db_id":"D011605"}]},{"id":"25877","type":"Chemical","text":["phenytoin"],"offsets":[[38,47]],"normalized":[{"db_name":"MESH","db_id":"D010672"}]},{"id":"25878","type":"Disease","text":["psychosis"],"offsets":[[94,103]],"normalized":[{"db_name":"MESH","db_id":"D011605"}]},{"id":"25879","type":"Disease","text":["epileptic"],"offsets":[[197,206]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"25880","type":"Disease","text":["psychosis"],"offsets":[[302,311]],"normalized":[{"db_name":"MESH","db_id":"D011605"}]},{"id":"25881","type":"Chemical","text":["phenytoin"],"offsets":[[322,331]],"normalized":[{"db_name":"MESH","db_id":"D010672"}]},{"id":"25882","type":"Disease","text":["trigeminal neuralgia"],"offsets":[[346,366]],"normalized":[{"db_name":"MESH","db_id":"D014277"}]},{"id":"25883","type":"Disease","text":["psychotic symptoms"],"offsets":[[409,427]],"normalized":[{"db_name":"MESH","db_id":"D011605"}]},{"id":"25884","type":"Chemical","text":["phenytoin"],"offsets":[[449,458]],"normalized":[{"db_name":"MESH","db_id":"D010672"}]},{"id":"25885","type":"Disease","text":["epileptic"],"offsets":[[477,486]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"25886","type":"Disease","text":["seizures"],"offsets":[[549,557]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]}],"events":[],"coreferences":[],"relations":[{"id":"25887","type":"CID","arg1_id":"25877","arg2_id":"25876","normalized":[]},{"id":"25888","type":"CID","arg1_id":"25877","arg2_id":"25878","normalized":[]},{"id":"25889","type":"CID","arg1_id":"25877","arg2_id":"25880","normalized":[]},{"id":"25890","type":"CID","arg1_id":"25877","arg2_id":"25883","normalized":[]},{"id":"25891","type":"CID","arg1_id":"25881","arg2_id":"25876","normalized":[]},{"id":"25892","type":"CID","arg1_id":"25881","arg2_id":"25878","normalized":[]},{"id":"25893","type":"CID","arg1_id":"25881","arg2_id":"25880","normalized":[]},{"id":"25894","type":"CID","arg1_id":"25881","arg2_id":"25883","normalized":[]},{"id":"25895","type":"CID","arg1_id":"25884","arg2_id":"25876","normalized":[]},{"id":"25896","type":"CID","arg1_id":"25884","arg2_id":"25878","normalized":[]},{"id":"25897","type":"CID","arg1_id":"25884","arg2_id":"25880","normalized":[]},{"id":"25898","type":"CID","arg1_id":"25884","arg2_id":"25883","normalized":[]}]}
{"id":"25899","document_id":"12617329","passages":[{"id":"25900","type":"title","text":["The effect of treatment with gum Arabic on gentamicin nephrotoxicity in rats: a preliminary study."],"offsets":[[0,98]]},{"id":"25901","type":"abstract","text":["In the present work we assessed the effect of treatment of rats with gum Arabic on acute renal failure induced by gentamicin (GM) nephrotoxicity. Rats were treated with the vehicle (2 mL\/kg of distilled water and 5% w\/v cellulose, 10 days), gum Arabic (2 mL\/kg of a 10% w\/v aqueous suspension of gum Arabic powder, orally for 10 days), or gum Arabic concomitantly with GM (80mg\/kg\/day intramuscularly, during the last six days of the treatment period). Nephrotoxicity was assessed by measuring the concentrations of creatinine and urea in the plasma and reduced glutathione (GSH) in the kidney cortex, and by light microscopic examination of kidney sections. The results indicated that concomitant treatment with gum Arabic and GM significantly increased creatinine and urea by about 183 and 239%, respectively (compared to 432 and 346%, respectively, in rats treated with cellulose and GM), and decreased that of cortical GSH by 21% (compared to 27% in the cellulose plus GM group) The GM-induced proximal tubular necrosis appeared to be slightly less severe in rats given GM together with gum Arabic than in those given GM and cellulose. It could be inferred that gum Arabic treatment has induced a modest amelioration of some of the histological and biochemical indices of GM nephrotoxicity. Further work is warranted on the effect of the treatments on renal functional aspects in models of chronic renal failure, and on the mechanism(s) involved."],"offsets":[[99,1549]]}],"entities":[{"id":"25902","type":"Chemical","text":["gum Arabic"],"offsets":[[29,39]],"normalized":[{"db_name":"MESH","db_id":"D006170"}]},{"id":"25903","type":"Chemical","text":["gentamicin"],"offsets":[[43,53]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"25904","type":"Disease","text":["nephrotoxicity"],"offsets":[[54,68]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"25905","type":"Chemical","text":["gum Arabic"],"offsets":[[168,178]],"normalized":[{"db_name":"MESH","db_id":"D006170"}]},{"id":"25906","type":"Disease","text":["acute renal 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{"id":"25954","document_id":"12523465","passages":[{"id":"25955","type":"title","text":["Visual hallucinations associated with zonisamide."],"offsets":[[0,49]]},{"id":"25956","type":"abstract","text":["Zonisamide is a broad-spectrum antiepileptic drug used to treat various types of seizures. Although visual hallucinations have not been reported as an adverse effect of this agent, we describe three patients who experienced complex visual hallucinations and altered mental status after zonisamide treatment was begun or its dosage increased. All three had been diagnosed earlier with epilepsy, and their electroencephalogram (EEG) findings were abnormal. During monitoring, visual hallucinations did not correlate with EEG readings, nor did video recording capture any of the described events. None of the patients had experienced visual hallucinations before this event. The only recent change in their treatment was the introduction or increased dosage of zonisamide. With either discontinuation or decreased dosage of the drug the symptoms disappeared and did not recur. Further observations and reports will help clarify this adverse effect. Until then, clinicians need to be aware of this possible complication associated with zonisamide."],"offsets":[[50,1093]]}],"entities":[{"id":"25957","type":"Disease","text":["Visual hallucinations"],"offsets":[[0,21]],"normalized":[{"db_name":"MESH","db_id":"D006212"}]},{"id":"25958","type":"Chemical","text":["zonisamide"],"offsets":[[38,48]],"normalized":[{"db_name":"MESH","db_id":"C022189"}]},{"id":"25959","type":"Chemical","text":["Zonisamide"],"offsets":[[50,60]],"normalized":[{"db_name":"MESH","db_id":"C022189"}]},{"id":"25960","type":"Disease","text":["seizures"],"offsets":[[131,139]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"25961","type":"Disease","text":["visual hallucinations"],"offsets":[[150,171]],"normalized":[{"db_name":"MESH","db_id":"D006212"}]},{"id":"25962","type":"Disease","text":["visual hallucinations"],"offsets":[[282,303]],"normalized":[{"db_name":"MESH","db_id":"D006212"}]},{"id":"25963","type":"Chemical","text":["zonisamide"],"offsets":[[336,346]],"normalized":[{"db_name":"MESH","db_id":"C022189"}]},{"id":"25964","type":"Disease","text":["epilepsy"],"offsets":[[434,442]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"25965","type":"Disease","text":["visual hallucinations"],"offsets":[[524,545]],"normalized":[{"db_name":"MESH","db_id":"D006212"}]},{"id":"25966","type":"Disease","text":["visual hallucinations"],"offsets":[[681,702]],"normalized":[{"db_name":"MESH","db_id":"D006212"}]},{"id":"25967","type":"Chemical","text":["zonisamide"],"offsets":[[808,818]],"normalized":[{"db_name":"MESH","db_id":"C022189"}]},{"id":"25968","type":"Chemical","text":["zonisamide"],"offsets":[[1082,1092]],"normalized":[{"db_name":"MESH","db_id":"C022189"}]}],"events":[],"coreferences":[],"relations":[{"id":"25969","type":"CID","arg1_id":"25958","arg2_id":"25957","normalized":[]},{"id":"25970","type":"CID","arg1_id":"25958","arg2_id":"25961","normalized":[]},{"id":"25971","type":"CID","arg1_id":"25958","arg2_id":"25962","normalized":[]},{"id":"25972","type":"CID","arg1_id":"25958","arg2_id":"25965","normalized":[]},{"id":"25973","type":"CID","arg1_id":"25958","arg2_id":"25966","normalized":[]},{"id":"25974","type":"CID","arg1_id":"25959","arg2_id":"25957","normalized":[]},{"id":"25975","type":"CID","arg1_id":"25959","arg2_id":"25961","normalized":[]},{"id":"25976","type":"CID","arg1_id":"25959","arg2_id":"25962","normalized":[]},{"id":"25977","type":"CID","arg1_id":"25959","arg2_id":"25965","normalized":[]},{"id":"25978","type":"CID","arg1_id":"25959","arg2_id":"25966","normalized":[]},{"id":"25979","type":"CID","arg1_id":"25963","arg2_id":"25957","normalized":[]},{"id":"25980","type":"CID","arg1_id":"25963","arg2_id":"25961","normalized":[]},{"id":"25981","type":"CID","arg1_id":"25963","arg2_id":"25962","normalized":[]},{"id":"25982","type":"CID","arg1_id":"25963","arg2_id":"25965","normalized":[]},{"id":"25983","type":"CID","arg1_id":"25963","arg2_id":"25966","normalized":[]},{"id":"25984","type":"CID","arg1_id":"25967","arg2_id":"25957","normalized":[]},{"id":"25985","type":"CID","arg1_id":"25967","arg2_id":"25961","normalized":[]},{"id":"25986","type":"CID","arg1_id":"25967","arg2_id":"25962","normalized":[]},{"id":"25987","type":"CID","arg1_id":"25967","arg2_id":"25965","normalized":[]},{"id":"25988","type":"CID","arg1_id":"25967","arg2_id":"25966","normalized":[]},{"id":"25989","type":"CID","arg1_id":"25968","arg2_id":"25957","normalized":[]},{"id":"25990","type":"CID","arg1_id":"25968","arg2_id":"25961","normalized":[]},{"id":"25991","type":"CID","arg1_id":"25968","arg2_id":"25962","normalized":[]},{"id":"25992","type":"CID","arg1_id":"25968","arg2_id":"25965","normalized":[]},{"id":"25993","type":"CID","arg1_id":"25968","arg2_id":"25966","normalized":[]}]}
{"id":"25994","document_id":"11961407","passages":[{"id":"25995","type":"title","text":["GLEPP1 receptor tyrosine phosphatase (Ptpro) in rat PAN nephrosis. A marker of acute podocyte injury."],"offsets":[[0,101]]},{"id":"25996","type":"abstract","text":["Glomerular epithelial protein 1 (GLEPP1) is a podocyte receptor membrane protein tyrosine phosphatase located on the apical cell membrane of visceral glomerular epithelial cell and foot processes. This receptor plays a role in regulating the structure and function of podocyte foot process. To better understand the utility of GLEPP1 as a marker of glomerular injury, the amount and distribution of GLEPP1 protein and mRNA were examined by immunohistochemistry, Western blot and RNase protection assay in a model of podocyte injury in the rat. Puromycin aminonucleoside nephrosis was induced by single intraperitoneal injection of puromycin aminonucleoside (PAN, 20 mg\/100g BW). Tissues were analyzed at 0, 5, 7, 11, 21, 45, 80 and 126 days after PAN injection so as to include both the acute phase of proteinuria associated with foot process effacement (days 5-11) and the chronic phase of proteinuria associated with glomerulosclerosis (days 45-126). At day 5, GLEPP1 protein and mRNA were reduced from the normal range (265.2 +\/- 79.6 x 10(6) moles\/glomerulus and 100%) to 15% of normal (41.8 +\/- 4.8 x 10(6) moles\/glomerulus, p < 0.005). This occurred in association with an increase in urinary protein content from 1.8 +\/- 1 to 99.0 +\/- 61 mg\/day (p < 0.001). In contrast, podocalyxin did not change significantly at this time. By day 11, GLEPP1 protein and mRNA had begun to return towards baseline. By day 45-126, at a time when glomerular scarring was present, GLEPP1 was absent from glomerulosclerotic areas although the total glomerular content of GLEPP1 was not different from normal. We conclude that GLEPP1 expression, unlike podocalyxin, reflects podocyte injury induced by PAN. GLEPP1 expression may be a useful marker of podocyte injury."],"offsets":[[102,1855]]}],"entities":[{"id":"25997","type":"Chemical","text":["tyrosine"],"offsets":[[16,24]],"normalized":[{"db_name":"MESH","db_id":"D014443"}]},{"id":"25998","type":"Chemical","text":["PAN"],"offsets":[[52,55]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"25999","type":"Disease","text":["nephrosis"],"offsets":[[56,65]],"normalized":[{"db_name":"MESH","db_id":"D009401"}]},{"id":"26000","type":"Chemical","text":["tyrosine"],"offsets":[[183,191]],"normalized":[{"db_name":"MESH","db_id":"D014443"}]},{"id":"26001","type":"Disease","text":["glomerular injury"],"offsets":[[451,468]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"26002","type":"Chemical","text":["Puromycin aminonucleoside"],"offsets":[[646,671]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"26003","type":"Disease","text":["nephrosis"],"offsets":[[672,681]],"normalized":[{"db_name":"MESH","db_id":"D009401"}]},{"id":"26004","type":"Chemical","text":["puromycin aminonucleoside"],"offsets":[[733,758]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"26005","type":"Chemical","text":["PAN"],"offsets":[[760,763]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"26006","type":"Chemical","text":["PAN"],"offsets":[[849,852]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"26007","type":"Disease","text":["proteinuria"],"offsets":[[904,915]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]},{"id":"26008","type":"Disease","text":["proteinuria"],"offsets":[[993,1004]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]},{"id":"26009","type":"Disease","text":["glomerulosclerosis"],"offsets":[[1021,1039]],"normalized":[{"db_name":"MESH","db_id":"D005921"}]},{"id":"26010","type":"Chemical","text":["PAN"],"offsets":[[1790,1793]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]}],"events":[],"coreferences":[],"relations":[{"id":"26011","type":"CID","arg1_id":"25998","arg2_id":"26007","normalized":[]},{"id":"26012","type":"CID","arg1_id":"25998","arg2_id":"26008","normalized":[]},{"id":"26013","type":"CID","arg1_id":"26002","arg2_id":"26007","normalized":[]},{"id":"26014","type":"CID","arg1_id":"26002","arg2_id":"26008","normalized":[]},{"id":"26015","type":"CID","arg1_id":"26004","arg2_id":"26007","normalized":[]},{"id":"26016","type":"CID","arg1_id":"26004","arg2_id":"26008","normalized":[]},{"id":"26017","type":"CID","arg1_id":"26005","arg2_id":"26007","normalized":[]},{"id":"26018","type":"CID","arg1_id":"26005","arg2_id":"26008","normalized":[]},{"id":"26019","type":"CID","arg1_id":"26006","arg2_id":"26007","normalized":[]},{"id":"26020","type":"CID","arg1_id":"26006","arg2_id":"26008","normalized":[]},{"id":"26021","type":"CID","arg1_id":"26010","arg2_id":"26007","normalized":[]},{"id":"26022","type":"CID","arg1_id":"26010","arg2_id":"26008","normalized":[]},{"id":"26023","type":"CID","arg1_id":"25998","arg2_id":"25999","normalized":[]},{"id":"26024","type":"CID","arg1_id":"25998","arg2_id":"26003","normalized":[]},{"id":"26025","type":"CID","arg1_id":"26002","arg2_id":"25999","normalized":[]},{"id":"26026","type":"CID","arg1_id":"26002","arg2_id":"26003","normalized":[]},{"id":"26027","type":"CID","arg1_id":"26004","arg2_id":"25999","normalized":[]},{"id":"26028","type":"CID","arg1_id":"26004","arg2_id":"26003","normalized":[]},{"id":"26029","type":"CID","arg1_id":"26005","arg2_id":"25999","normalized":[]},{"id":"26030","type":"CID","arg1_id":"26005","arg2_id":"26003","normalized":[]},{"id":"26031","type":"CID","arg1_id":"26006","arg2_id":"25999","normalized":[]},{"id":"26032","type":"CID","arg1_id":"26006","arg2_id":"26003","normalized":[]},{"id":"26033","type":"CID","arg1_id":"26010","arg2_id":"25999","normalized":[]},{"id":"26034","type":"CID","arg1_id":"26010","arg2_id":"26003","normalized":[]}]}
{"id":"26035","document_id":"9401499","passages":[{"id":"26036","type":"title","text":["Ticlopidine-induced aplastic anemia: report of three Chinese patients and review of the literature."],"offsets":[[0,99]]},{"id":"26037","type":"abstract","text":["In this study, three Chinese patients with ticlopidine-induced aplastic anemia were reported and another 13 patients in the English literature were reviewed. We attempted to find underlying similarities, evaluate the risk factors, and identify appropriate treatment for this complication. All but one of the patients were over 60 years old, and the 6 who died were all older than 65. Therefore, old age may be a risk factor for developing this complication. Agranulocytosis occurred 3-20 weeks after initiation of ticlopidine, so frequent examination of white cell count during treatment is recommended. There seemed to be no direct correlation between the dose or duration used and the severity of bone marrow suppression. Treatment for ticlopidine-induced aplastic anemia with colony-stimulating factors seemed to have little effect. The fact that 5 of the 6 patients who received concurrent calcium channel blockers died, should alert clinicians to be more cautious when using these two drugs simultaneously."],"offsets":[[100,1111]]}],"entities":[{"id":"26038","type":"Chemical","text":["Ticlopidine"],"offsets":[[0,11]],"normalized":[{"db_name":"MESH","db_id":"D013988"}]},{"id":"26039","type":"Disease","text":["aplastic anemia"],"offsets":[[20,35]],"normalized":[{"db_name":"MESH","db_id":"D000741"}]},{"id":"26040","type":"Chemical","text":["ticlopidine"],"offsets":[[143,154]],"normalized":[{"db_name":"MESH","db_id":"D013988"}]},{"id":"26041","type":"Disease","text":["aplastic anemia"],"offsets":[[163,178]],"normalized":[{"db_name":"MESH","db_id":"D000741"}]},{"id":"26042","type":"Disease","text":["Agranulocytosis"],"offsets":[[558,573]],"normalized":[{"db_name":"MESH","db_id":"D000380"}]},{"id":"26043","type":"Chemical","text":["ticlopidine"],"offsets":[[614,625]],"normalized":[{"db_name":"MESH","db_id":"D013988"}]},{"id":"26044","type":"Disease","text":["bone marrow suppression"],"offsets":[[799,822]],"normalized":[{"db_name":"MESH","db_id":"D001855"}]},{"id":"26045","type":"Chemical","text":["ticlopidine"],"offsets":[[838,849]],"normalized":[{"db_name":"MESH","db_id":"D013988"}]},{"id":"26046","type":"Disease","text":["aplastic anemia"],"offsets":[[858,873]],"normalized":[{"db_name":"MESH","db_id":"D000741"}]},{"id":"26047","type":"Chemical","text":["calcium"],"offsets":[[994,1001]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]}],"events":[],"coreferences":[],"relations":[{"id":"26048","type":"CID","arg1_id":"26038","arg2_id":"26039","normalized":[]},{"id":"26049","type":"CID","arg1_id":"26038","arg2_id":"26041","normalized":[]},{"id":"26050","type":"CID","arg1_id":"26038","arg2_id":"26046","normalized":[]},{"id":"26051","type":"CID","arg1_id":"26040","arg2_id":"26039","normalized":[]},{"id":"26052","type":"CID","arg1_id":"26040","arg2_id":"26041","normalized":[]},{"id":"26053","type":"CID","arg1_id":"26040","arg2_id":"26046","normalized":[]},{"id":"26054","type":"CID","arg1_id":"26043","arg2_id":"26039","normalized":[]},{"id":"26055","type":"CID","arg1_id":"26043","arg2_id":"26041","normalized":[]},{"id":"26056","type":"CID","arg1_id":"26043","arg2_id":"26046","normalized":[]},{"id":"26057","type":"CID","arg1_id":"26045","arg2_id":"26039","normalized":[]},{"id":"26058","type":"CID","arg1_id":"26045","arg2_id":"26041","normalized":[]},{"id":"26059","type":"CID","arg1_id":"26045","arg2_id":"26046","normalized":[]},{"id":"26060","type":"CID","arg1_id":"26038","arg2_id":"26042","normalized":[]},{"id":"26061","type":"CID","arg1_id":"26040","arg2_id":"26042","normalized":[]},{"id":"26062","type":"CID","arg1_id":"26043","arg2_id":"26042","normalized":[]},{"id":"26063","type":"CID","arg1_id":"26045","arg2_id":"26042","normalized":[]}]}
{"id":"26064","document_id":"2273650","passages":[{"id":"26065","type":"title","text":["Facilitation of memory retrieval by pre-test morphine and its state dependency in the step-through type passive avoidance learning test in mice."],"offsets":[[0,144]]},{"id":"26066","type":"abstract","text":["Amnesia produced by scopolamine and cycloheximide were reversed by morphine given 30 min before the test trial (pre-test), and pre-test morphine also facilitated the memory retrieval in the animals administered naloxone during the training trial. Similarly, pre-test scopolamine partially reversed the scopolamine-induced amnesia, but not significantly; and pre-test cycloheximide failed to reverse the cycloheximide-induced amnesia. These results suggest that the facilitation of memory retrieval by pre-test morphine might be the direct action of morphine rather than a state dependent effect."],"offsets":[[145,740]]}],"entities":[{"id":"26067","type":"Chemical","text":["morphine"],"offsets":[[45,53]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"26068","type":"Disease","text":["Amnesia"],"offsets":[[145,152]],"normalized":[{"db_name":"MESH","db_id":"D000647"}]},{"id":"26069","type":"Chemical","text":["scopolamine"],"offsets":[[165,176]],"normalized":[{"db_name":"MESH","db_id":"D012601"}]},{"id":"26070","type":"Chemical","text":["cycloheximide"],"offsets":[[181,194]],"normalized":[{"db_name":"MESH","db_id":"D003513"}]},{"id":"26071","type":"Chemical","text":["morphine"],"offsets":[[212,220]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"26072","type":"Chemical","text":["morphine"],"offsets":[[281,289]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"26073","type":"Chemical","text":["naloxone"],"offsets":[[356,364]],"normalized":[{"db_name":"MESH","db_id":"D009270"}]},{"id":"26074","type":"Chemical","text":["scopolamine"],"offsets":[[412,423]],"normalized":[{"db_name":"MESH","db_id":"D012601"}]},{"id":"26075","type":"Chemical","text":["scopolamine"],"offsets":[[447,458]],"normalized":[{"db_name":"MESH","db_id":"D012601"}]},{"id":"26076","type":"Disease","text":["amnesia"],"offsets":[[467,474]],"normalized":[{"db_name":"MESH","db_id":"D000647"}]},{"id":"26077","type":"Chemical","text":["cycloheximide"],"offsets":[[512,525]],"normalized":[{"db_name":"MESH","db_id":"D003513"}]},{"id":"26078","type":"Chemical","text":["cycloheximide"],"offsets":[[548,561]],"normalized":[{"db_name":"MESH","db_id":"D003513"}]},{"id":"26079","type":"Disease","text":["amnesia"],"offsets":[[570,577]],"normalized":[{"db_name":"MESH","db_id":"D000647"}]},{"id":"26080","type":"Chemical","text":["morphine"],"offsets":[[655,663]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"26081","type":"Chemical","text":["morphine"],"offsets":[[694,702]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]}],"events":[],"coreferences":[],"relations":[{"id":"26082","type":"CID","arg1_id":"26069","arg2_id":"26068","normalized":[]},{"id":"26083","type":"CID","arg1_id":"26069","arg2_id":"26076","normalized":[]},{"id":"26084","type":"CID","arg1_id":"26069","arg2_id":"26079","normalized":[]},{"id":"26085","type":"CID","arg1_id":"26074","arg2_id":"26068","normalized":[]},{"id":"26086","type":"CID","arg1_id":"26074","arg2_id":"26076","normalized":[]},{"id":"26087","type":"CID","arg1_id":"26074","arg2_id":"26079","normalized":[]},{"id":"26088","type":"CID","arg1_id":"26075","arg2_id":"26068","normalized":[]},{"id":"26089","type":"CID","arg1_id":"26075","arg2_id":"26076","normalized":[]},{"id":"26090","type":"CID","arg1_id":"26075","arg2_id":"26079","normalized":[]},{"id":"26091","type":"CID","arg1_id":"26070","arg2_id":"26068","normalized":[]},{"id":"26092","type":"CID","arg1_id":"26070","arg2_id":"26076","normalized":[]},{"id":"26093","type":"CID","arg1_id":"26070","arg2_id":"26079","normalized":[]},{"id":"26094","type":"CID","arg1_id":"26077","arg2_id":"26068","normalized":[]},{"id":"26095","type":"CID","arg1_id":"26077","arg2_id":"26076","normalized":[]},{"id":"26096","type":"CID","arg1_id":"26077","arg2_id":"26079","normalized":[]},{"id":"26097","type":"CID","arg1_id":"26078","arg2_id":"26068","normalized":[]},{"id":"26098","type":"CID","arg1_id":"26078","arg2_id":"26076","normalized":[]},{"id":"26099","type":"CID","arg1_id":"26078","arg2_id":"26079","normalized":[]}]}
{"id":"26100","document_id":"10683478","passages":[{"id":"26101","type":"title","text":["Test conditions influence the response to a drug challenge in rodents."],"offsets":[[0,70]]},{"id":"26102","type":"abstract","text":["These studies were conducted to examine the differential response to a drug challenge under varied experimental test conditions routinely employed to study drug-induced behavioral and neurophysiological responses in rodents. Apomorphine, a nonselective dopamine agonist, was selected due to its biphasic behavioral effects, its ability to induce hypothermia, and to produce distinct changes to dopamine turnover in the rodent brain. From such experiments there is evidence that characterization and detection of apomorphine-induced activity in rodents critically depends upon the test conditions employed. In rats, detection of apomorphine-induced hyperactivity was facilitated by a period of acclimatization to the test conditions. Moreover, test conditions can impact upon other physiological responses to apomorphine such as drug-induced hypothermia. In mice, apomorphine produced qualitatively different responses under novel conditions when compared to those behaviors elicited in the home test cage. Drug-induced gross activity counts were increased in the novel exploratory box only, while measures of stereotypic behavior were similar in both. By contrast, apomorphine-induced locomotion was more prominent in the novel exploratory box. Dopamine turnover ratios (DOPAC:DA and HVA:DA) were found to be lower in those animals exposed to the exploratory box when compared to their home cage counterparts. However, apomorphine-induced reductions in striatal dopamine turnover were detected in both novel and home cage environments. The implications of these findings are discussed with particular emphasis upon conducting psychopharmacological challenge tests in rodents."],"offsets":[[71,1746]]}],"entities":[{"id":"26103","type":"Chemical","text":["Apomorphine"],"offsets":[[296,307]],"normalized":[{"db_name":"MESH","db_id":"D001058"}]},{"id":"26104","type":"Chemical","text":["dopamine agonist"],"offsets":[[324,340]],"normalized":[{"db_name":"MESH","db_id":"D018491"}]},{"id":"26105","type":"Disease","text":["hypothermia"],"offsets":[[417,428]],"normalized":[{"db_name":"MESH","db_id":"D007035"}]},{"id":"26106","type":"Chemical","text":["dopamine"],"offsets":[[465,473]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"26107","type":"Chemical","text":["apomorphine"],"offsets":[[583,594]],"normalized":[{"db_name":"MESH","db_id":"D001058"}]},{"id":"26108","type":"Chemical","text":["apomorphine"],"offsets":[[699,710]],"normalized":[{"db_name":"MESH","db_id":"D001058"}]},{"id":"26109","type":"Disease","text":["hyperactivity"],"offsets":[[719,732]],"normalized":[{"db_name":"MESH","db_id":"D006948"}]},{"id":"26110","type":"Chemical","text":["apomorphine"],"offsets":[[879,890]],"normalized":[{"db_name":"MESH","db_id":"D001058"}]},{"id":"26111","type":"Disease","text":["hypothermia"],"offsets":[[912,923]],"normalized":[{"db_name":"MESH","db_id":"D007035"}]},{"id":"26112","type":"Chemical","text":["apomorphine"],"offsets":[[934,945]],"normalized":[{"db_name":"MESH","db_id":"D001058"}]},{"id":"26113","type":"Chemical","text":["apomorphine"],"offsets":[[1236,1247]],"normalized":[{"db_name":"MESH","db_id":"D001058"}]},{"id":"26114","type":"Chemical","text":["Dopamine"],"offsets":[[1316,1324]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"26115","type":"Chemical","text":["DOPAC"],"offsets":[[1342,1347]],"normalized":[{"db_name":"MESH","db_id":"D015102"}]},{"id":"26116","type":"Chemical","text":["DA"],"offsets":[[1348,1350]],"normalized":[{"db_name":"MESH","db_id":"D018491"}]},{"id":"26117","type":"Chemical","text":["HVA"],"offsets":[[1355,1358]],"normalized":[{"db_name":"MESH","db_id":"D006719"}]},{"id":"26118","type":"Chemical","text":["DA"],"offsets":[[1359,1361]],"normalized":[{"db_name":"MESH","db_id":"D018491"}]},{"id":"26119","type":"Chemical","text":["apomorphine"],"offsets":[[1490,1501]],"normalized":[{"db_name":"MESH","db_id":"D001058"}]},{"id":"26120","type":"Chemical","text":["dopamine"],"offsets":[[1533,1541]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]}],"events":[],"coreferences":[],"relations":[{"id":"26121","type":"CID","arg1_id":"26103","arg2_id":"26105","normalized":[]},{"id":"26122","type":"CID","arg1_id":"26103","arg2_id":"26111","normalized":[]},{"id":"26123","type":"CID","arg1_id":"26107","arg2_id":"26105","normalized":[]},{"id":"26124","type":"CID","arg1_id":"26107","arg2_id":"26111","normalized":[]},{"id":"26125","type":"CID","arg1_id":"26108","arg2_id":"26105","normalized":[]},{"id":"26126","type":"CID","arg1_id":"26108","arg2_id":"26111","normalized":[]},{"id":"26127","type":"CID","arg1_id":"26110","arg2_id":"26105","normalized":[]},{"id":"26128","type":"CID","arg1_id":"26110","arg2_id":"26111","normalized":[]},{"id":"26129","type":"CID","arg1_id":"26112","arg2_id":"26105","normalized":[]},{"id":"26130","type":"CID","arg1_id":"26112","arg2_id":"26111","normalized":[]},{"id":"26131","type":"CID","arg1_id":"26113","arg2_id":"26105","normalized":[]},{"id":"26132","type":"CID","arg1_id":"26113","arg2_id":"26111","normalized":[]},{"id":"26133","type":"CID","arg1_id":"26119","arg2_id":"26105","normalized":[]},{"id":"26134","type":"CID","arg1_id":"26119","arg2_id":"26111","normalized":[]},{"id":"26135","type":"CID","arg1_id":"26103","arg2_id":"26109","normalized":[]},{"id":"26136","type":"CID","arg1_id":"26107","arg2_id":"26109","normalized":[]},{"id":"26137","type":"CID","arg1_id":"26108","arg2_id":"26109","normalized":[]},{"id":"26138","type":"CID","arg1_id":"26110","arg2_id":"26109","normalized":[]},{"id":"26139","type":"CID","arg1_id":"26112","arg2_id":"26109","normalized":[]},{"id":"26140","type":"CID","arg1_id":"26113","arg2_id":"26109","normalized":[]},{"id":"26141","type":"CID","arg1_id":"26119","arg2_id":"26109","normalized":[]}]}