Effects of cisapride on symptoms and postcibal small-bowel motor function in patients with irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome is a common cause of abdominal pain and discomfort and may be related to disordered gastrointestinal motility. Our aim was to assess the effects of long-term treatment with a prokinetic agent, cisapride, on postprandial jejunal motility and symptoms in the irritable bowel syndrome (IBS). METHODS: Thirty-eight patients with IBS (constipation-predominant, n = 17; diarrhoea-predominant, n = 21) underwent 24-h ambulatory jejunal manometry before and after 12 week's treatment [cisapride, 5 mg three times daily (n = 19) or placebo (n = 19)]. RESULTS: In diarrhoea-predominant patients significant differences in contraction characteristics were observed between the cisapride and placebo groups. In cisapride-treated diarrhoea-predominant patients the mean contraction amplitude was higher (29.3 +/- 3.2 versus 24.9 +/- 2.6 mm Hg, cisapride versus placebo (P < 0.001); pretreatment, 25.7 +/- 6.0 mm Hg), the mean contraction duration longer (3.4 +/- 0.2 versus 3.0 +/- 0.2 sec, cisapride versus placebo (P < 0.001); pretreatment, 3.1 +/- 0.5 sec), and the mean contraction frequency lower (2.0 +/- 0.2 versus 2.5 +/- 0.4 cont./min, cisapride versus placebo (P < 0.001); pretreatment, 2.5 +/- 1.1 cont./min] than patients treated with placebo. No significant differences in jejunal motility were found in the constipation-predominant IBS group. Symptoms were assessed by using a visual analogue scale before and after treatment. Symptom scores relating to the severity of constipation were lower in cisapride-treated constipation-predominant IBS patients [score, 54 +/- 5 versus 67 +/- 14 mm, cisapride versus placebo (P < 0.05); pretreatment, 62 +/- 19 mm]. Diarrhoea-predominant IBS patients had a higher pain score after cisapride therapy [score, 55 +/- 15 versus 34 +/- 12 mm, cisapride versus placebo (P < 0.05); pretreatment, 67 +/- 19 mm]. CONCLUSION: Cisapride affects jejunal contraction characteristics and some symptoms in IBS.

cisapride

irritable bowel syndrome

Irritable bowel syndrome

abdominal pain

disordered gastrointestinal motility

cisapride

irritable bowel syndrome

IBS

IBS

constipation

diarrhoea

cisapride

diarrhoea

cisapride

cisapride

diarrhoea

cisapride

cisapride

cisapride

constipation

IBS

constipation

cisapride

constipation

IBS

cisapride

Diarrhoea

IBS

pain

cisapride

cisapride

Cisapride

IBS


Clarithromycin-induced ventricular tachycardia.

Clarithromycin is a relatively new macrolide antibiotic that offers twice-daily dosing. It differs from erythromycin only in the methylation of the hydroxyl group at position 6. Although the side-effect profile of erythromycin is established, including gastroenteritis and interactions with other drugs subject to hepatic mixed-function oxidase metabolism, experience with the newer macrolides is still being recorded. Cardiotoxicity has been demonstrated after both intravenous and oral administration of erythromycin but has never been reported with the newer macrolides. We report a case of ventricular dysrhythmias that occurred after six therapeutic doses of clarithromycin. The dysrhythmias resolved after discontinuation of the drug.

Clarithromycin

ventricular tachycardia

Clarithromycin

macrolide

erythromycin

erythromycin

gastroenteritis

macrolides

Cardiotoxicity

erythromycin

macrolides

ventricular dysrhythmias

clarithromycin

dysrhythmias


Persistent nephrogenic diabetes insipidus following lithium therapy.

We report the case of a patient who developed severe hypernatraemic dehydration following a head injury. Ten years previously he had been diagnosed to have lithium-induced nephrogenic diabetes insipidus, and lithium therapy had been discontinued. He remained thirsty and polyuric despite cessation of lithium and investigations on admission showed him to have normal osmoregulated thirst and vasopressin secretion, with clear evidence of nephrogenic diabetes insipidus. Lithium induced nephrogenic diabetes insipidus is considered to be reversible on cessation of therapy but polyuria persisted in this patient for ten years after lithium was stopped. We discuss the possible renal mechanisms and the implications for management of patients with lithium-induced nephrogenic diabetes insipidus.

nephrogenic diabetes insipidus

lithium

dehydration

head injury

lithium

nephrogenic diabetes insipidus

lithium

polyuric

lithium

vasopressin

nephrogenic diabetes insipidus

Lithium

nephrogenic diabetes insipidus

polyuria

lithium

lithium

nephrogenic diabetes insipidus


Late cardiotoxicity after treatment for a malignant bone tumor.

Cardiac function was assessed in long-term survivors of malignant bone tumors who were treated according to Rosen's T5 or T10 protocol, both including doxorubicin. Thirty-one patients, age 10-45 years (median age 17.8 years) were evaluated 2.3-14.1 years (median 8.9 years) following completion of treatment. Cumulative doses of doxorubicin were 225-550 mg/m2 (median dose 360). The evaluation consisted of a history, physical examination, electrocardiogram (ECG), signal averaged ECG, 24-hour ambulatory ECG, echocardiography and radionuclide angiography. Eighteen of 31 (58%) patients showed cardiac toxicity, defined as having one or more of the following abnormalities: late potentials, complex ventricular arrhythmias, left ventricular dilation, decreased shortening fraction, or decreased ejection fraction. The incidence of cardiac abnormalities increased with length of follow-up (P< or = .05). No correlation could be demonstrated between cumulative dose of doxorubicin and cardiac status, except for heart rate variability. When adjusted to body surface area, the left ventricular posterior wall thickness (LVPW index) was decreased in all patients. The incidence of doxorubicin-induced cardiotoxicity is high and increases with follow-up, irrespective of cumulative dose. Life-long cardiac follow-up in these patients is warranted. The results of our study suggest that heart rate variability and LVPW index could be sensitive indicators for cardiotoxicity.

cardiotoxicity

bone tumor

bone tumors

Rosen's T5 or T10 protocol

doxorubicin

doxorubicin

cardiac toxicity

ventricular arrhythmias

ventricular dilation

cardiac abnormalities

doxorubicin

doxorubicin

cardiotoxicity

cardiotoxicity


Venous complications of midazolam versus diazepam.

Although some studies have suggested fewer venous complications are associated with midazolam than with diazepam for endoscopic procedures, this variable has not been well documented. We prospectively evaluated the incidence of venous complications after intravenous injection of diazepam or midazolam in 122 consecutive patients undergoing colonoscopy and esophagogastroduodenoscopy. Overall, venous complications were more frequent with diazepam (22 of 62 patients) than with midazolam (4 of 60 patients) (p < 0.001). A palpable venous cord was present in 23% (14 of 62) of patients in the diazepam group, compared with 2% (1 of 60 patients) in the midazolam group (p < 0.002). Pain at the injection site occurred in 35% (22 of 62) of patients in the diazepam group compared with 7% (4 of 60 patients) in the midazolam group (p < 0.001). Swelling and warmth at the injection site were not significantly different between the two groups. Smoking, nonsteroidal anti-inflammatory drug use, intravenous catheter site, dwell time of the needle, alcohol use, and pain during the injection had no effect on the incidence of venous complications.

Venous complications

midazolam

diazepam

venous complications

midazolam

diazepam

venous complications

diazepam

midazolam

venous complications

diazepam

midazolam

diazepam

midazolam

Pain

diazepam

midazolam

Swelling

alcohol

pain

venous complications


Tetany and rhabdomyolysis due to surreptitious furosemide--importance of magnesium supplementation.

Diuretics may induce hypokalemia, hypocalcemia and hypomagnesemia. While severe hypokalemia may cause muscle weakness, severe hypomagnesemia is associated with muscle spasms and tetany which cannot be corrected by potassium and calcium supplementation alone (1,2). Surreptitious diuretic ingestion has been described, mainly in women who are concerned that they are obese or edematous. Symptomatic hypokalemia has been reported in such patients (3-7) and in one case hypocalcemia was observed (8), but the effects of magnesium depletion were not noted in these patients.

Tetany

rhabdomyolysis

furosemide

magnesium

hypokalemia

hypocalcemia

hypomagnesemia

hypokalemia

muscle weakness

hypomagnesemia

muscle spasms

tetany

potassium

calcium

obese

edematous

hypokalemia

hypocalcemia

magnesium


Loss of glutamate decarboxylase mRNA-containing neurons in the rat dentate gyrus following pilocarpine-induced seizures.

In situ hybridization methods were used to determine if glutamic acid decarboxylase (GAD) mRNA-containing neurons within the hilus of the dentate gyrus are vulnerable to seizure-induced damage in a model of chronic seizures. Sprague-Dawley rats were injected intraperitoneally with pilocarpine, and the hippocampal formation was studied histologically at 1, 2, 4, and 8 week intervals after pilocarpine-induced seizures. In situ hybridization histochemistry, using a digoxigenin-labeled GAD cRNA probe, demonstrated a substantial decrease in the number of GAD mRNA-containing neurons in the hilus of the dentate gyrus in the pilocarpine-treated rats as compared to controls at all time intervals. Additional neuronanatomical studies, including cresyl violet staining, neuronal degeneration methods, and histochemical localization of glial fibrillary acidic protein, suggested that the decrease in the number of GAD mRNA-containing neurons was related to neuronal loss rather than to a decrease in GAD mRNA levels. The loss of GAD mRNA-containing neurons in the hilus contrasted with the relative preservation of labeled putative basket cells along the inner margin of the granule cell layer. Quantitative analyses of labeled neurons in three regions of the dentate gyrus in the 1 and 2 week groups showed statistically significant decreases in the mean number of GAD mRNA-containing neurons in the hilus of both groups of experimental animals. No significant differences were found in the molecular layer or the granule cell layer, which included labeled neurons along the lower margin of the granule cell layer. The results indicate that, in this model, a subpopulation of GAD mRNA-containing neurons within the dentate gyrus is selectively vulnerable to seizure-induced damage. Such differential vulnerability appears to be another indication of the heterogeneity of GABA neurons.

glutamate

pilocarpine

seizures

glutamic acid

seizure

seizures

pilocarpine

pilocarpine

seizures

digoxigenin

pilocarpine

cresyl violet

neuronal degeneration

neuronal loss

seizure

GABA


Protective effect of misoprostol on indomethacin induced renal dysfunction in elderly patients.

OBJECTIVE: To evaluate the possible protective effects of misoprostol on renal function in hospitalized elderly patients treated with indomethacin. METHODS: Forty-five hospitalized elderly patients (> 65 years old) who required therapy with nonsteroidal antiinflammatory drugs (NSAID) were randomly assigned to receive either indomethacin, 150 mg/day (Group A), or indomethacin 150 mg/day plus misoprostol at 0.6 mg/day (Group B). Laboratory variables of renal function [serum creatinine, blood urea nitrogen (BUN) and electrolytes] were evaluated before initiation of therapy and every 2 days, until termination of the study (a period of at least 6 days). Response to treatment was estimated by the visual analog scale for severity of pain. RESULTS: Forty-two patients completed the study, 22 in Group A and 20 in Group B. BUN and creatinine increased by > 50% of baseline levels in 54 and 45% of Group A patients, respectively, compared to only 20 and 10% of Group B patients (p < 0.05). Potassium (K) increment of 0.6 mEq/l or more was observed in 50% of Group A, but in only 15% of Group B patients (p < 0.05). The mean increments in BUN, creatinine, and K were reduced by 63, 80, and 42%, respectively, in Group B patients compared to Group A. Response to treatment did not differ significantly between the 2 groups. CONCLUSION: Hospitalized elderly patients are at risk for developing indomethacin related renal dysfunction. Addition of misoprostol can minimize this renal impairment without affecting pain control.

misoprostol

indomethacin

renal dysfunction

misoprostol

indomethacin

indomethacin

indomethacin

misoprostol

creatinine

blood urea nitrogen

BUN

pain

BUN

creatinine

Potassium

K

BUN

creatinine

K

indomethacin

renal dysfunction

misoprostol

renal impairment

pain


Nephrotoxic effects of aminoglycoside treatment on renal protein reabsorption and accumulation.

To quantify the effects of gentamicin, kanamycin and netilmicin on renal protein reabsorption and accumulation, these drugs were administered to rats intraperitoneally (30 mg/kg/day) for 7, 14 or 21 days. Scanning electron microscopy of the glomerular endothelia, urinary measurements of sodium, potassium, endogenous lysozyme, N-acetyl-beta-D-glucosaminidase (NAG) as well as clearance and accumulation experiments after i.v. administration of egg-white lysozyme and measurements of inulin clearance (GFR) were done in each treatment group. Gentamicin administration decreased diameter, density and shape of endothelial fenestrae. Kanamycin and netilmicin appeared to have no effect at the dose used. All three aminoglycosides decreased GFR and increased urinary excretion of sodium and potassium. While gentamicin and kanamycin decreased the percentage reabsorption and accumulation of lysozyme after i.v. administration of egg-white lysozyme netilmicin had no effect. Daily excretion of total protein, endogenous lysozyme and NAG increased only after treatment with kanamycin and gentamicin. Thus, aminoglycosides may act as nephrotoxicants at glomerular and/or tubular level inducing impairment of renal reabsorption and accumulation of proteins.

Nephrotoxic

aminoglycoside

gentamicin

kanamycin

netilmicin

sodium

potassium

Gentamicin

Kanamycin

netilmicin

aminoglycosides

sodium

potassium

gentamicin

kanamycin

netilmicin

kanamycin

gentamicin

aminoglycosides

impairment of renal reabsorption


Pharmacology of GYKI-41 099 (chlorpropanol, Tobanum) a new potent beta-adrenergic antagonist.

The compound GYKI-41 099, as a beta-adrenergic antagonist, is 3-8 times more potent than propranolol in vitro and in vivo. Its antiarrhythmic effectiveness surpasses that of propranolol and pindolol inhibiting the ouabain arrhythmia in dogs and cats. GYKI-41 900 has a negligible cardiodepressant activity; it is not cardioselective. The compound shows a rapid and long lasting effect. There was a prolonged elimination of the radioactivity after the injection of 14C-41 099 to rats and dogs. The half life of the unlabeled substance in humans was more than 10 hours.

GYKI-41 099

chlorpropanol

Tobanum

GYKI-41 099

propranolol

propranolol

pindolol

ouabain

arrhythmia

GYKI-41 900

14C-41 099


Chorea associated with oral contraception.

Three patients developed chorea while receiving oral contraceptives. Two were young patients whose chorea developed long after treatment had been started and disappeared soon after it had been discontinued. The third patient had acute amphetamine-induced chorea after prolonged oral contraception. Prolonged administration of female sex hormones is a possible cause of chorea in women who have not previously had chorea or rheumatic fever.

Chorea

oral contraception

chorea

oral contraceptives

chorea

amphetamine

chorea

oral contraception

chorea

chorea

rheumatic fever


Reversal of ammonia coma in rats by L-dopa: a peripheral effect.

Ammonia coma was produced in rats within 10 to 15 minutes of an intraperitonealinjection of 1.7 mmol NH4CL. This coma was prevented with 1.68 mmol L-dopa given by gastric intubation 15 minutes before the ammonium salt injection. The effect of L-dopa was correlated with a decrease in blood and brain ammonia, an increase in brain dopamine, and an increase in renal excretion of ammonia and urea. Intraventricular infusion of dopamine sufficient to raise the brain dopamine to the same extent did not prevent the ammonia coma nor affect the blood and brain ammonia concentrations. Bilateral nephrectomy eliminated the beneficial effect of L-dopa on blood and brain ammonia and the ammonia coma was not prevented. Thus, the reduction in blood and brain ammonia and the prevention of ammonia coma after L-dopa, can be accounted for by the peripheral effect of dopamine on renal function rather than its central action. These results provide a reasonable explanation for the beneficial effects observed in some encephalopathic patients receiving L-dopa.

ammonia

coma

L-dopa

Ammonia

coma

coma

L-dopa

ammonium salt

L-dopa

ammonia

dopamine

ammonia

urea

dopamine

dopamine

ammonia

coma

ammonia

L-dopa

ammonia

ammonia

coma

ammonia

ammonia

coma

L-dopa

dopamine

encephalopathic

L-dopa


Heparin-induced thrombocytopenia after liver transplantation.

BACKGROUND: Unfractionated heparin sodium (UFH) or low-molecular weight heparin (LMWH) is used in anticoagulant protocols at several institutions to prevent thrombosis after liver transplantation. Heparin-induced thrombocytopenia (HIT) is an adverse immune-mediated reaction to heparin, resulting in platelet count decreases of more than 50%. The frequencies of HIT after liver transplantation and platelet factor 4/heparin-reactive antibody (HIT antibody) positivity in liver transplantation patients, however, are unknown. PATIENTS AND METHODS: The 32 men and 20 women underwent living donor liver transplantation. We started LMWH (25 IU/kg/h) on postoperative day (POD) 1, switching to UFH (5000 U/d) on POD 2 or 3. The dose of UFH was changed according to the activated clotting time level. HIT antibody levels were measured the day before surgery and on POD 7 and 14. Platelet count was measured daily for 3 weeks. RESULTS: The average platelet counts preoperatively, and on POD 7, 14, and 21 were 65, 88, 149, and 169 x 10(9)/L, respectively. Two patients developed hepatic artery thrombosis on POD 11 and 19, respectively, although they were HIT antibody-negative and their platelet counts were stable. In 2 other patients, the platelet count decreased suddenly from 107 x 10(9)/L on POD 4 to 65 x 10(9)/L on POD 6 and from 76 x 10(9)/L on POD 7 to 33 x 10(9)/L on POD 9, respectively. The heparin-induced platelet aggregation test was negative in these patients. The percentage of HIT antibody-positive patients was 0.5% preoperatively, 5.6% on POD 7, and 5.6% on POD 14. None of the subjects/patients developed UFH-related HIT. CONCLUSIONS: In our series, the occurrence of HIT after liver transplantation was uncommon.

Heparin

thrombocytopenia

Unfractionated heparin sodium

UFH

low-molecular weight heparin

thrombosis

Heparin

thrombocytopenia

HIT

heparin

HIT

heparin

HIT

UFH

UFH

HIT

thrombosis

HIT

heparin

platelet aggregation

HIT

UFH

HIT

HIT


PTU-associated vasculitis in a girl with Turner Syndrome and Graves' disease.

Palpable purpura is a concerning clinical finding in pediatric patients and can have many causes, including infectious and autoimmune processes. A rare cause, drug-induced vasculitis, may result from the production of antineutrophil cytoplasmic antibodies (ANCAs) in response to a medication. We report a girl with Turner syndrome and Graves' disease who presented with palpable purpuric lesions. The diagnosis of propylthiouracil (PTU)-associated vasculitis was made by observation of consistent clinical features, the detection of elevated ANA and ANCA in the blood, and the observed clinical resolution of symptoms following withdrawal of PTU. Subsequent treatment of persistent hyperthyroidism with radioablation did not result in an exacerbation of the vasculitis, a complication described in prior case reports.

PTU

vasculitis

Turner Syndrome

Graves' disease

purpura

vasculitis

Turner syndrome

Graves' disease

purpuric lesions

propylthiouracil

PTU

vasculitis

PTU

hyperthyroidism

vasculitis


Succinylcholine-induced masseter muscle rigidity during bronchoscopic removal of a tracheal foreign body.

Masseter muscle rigidity during general anesthesia is considered an early warning sign of a possible episode of malignant hyperthermia. The decision whether to continue or discontinue the procedure depends on the urgency of the surgery and severity of masseter muscle rigidity. Here, we describe a case of severe masseter muscle rigidity (jaw of steel) after succinylcholine (Sch) administration during general anesthetic management for rigid bronchoscopic removal of a tracheal foreign body. Anesthesia was continued uneventfully with propofol infusion while all facilities were available to detect and treat malignant hyperthermia.

Succinylcholine

masseter muscle rigidity

Masseter muscle rigidity

malignant hyperthermia

masseter muscle rigidity

masseter muscle rigidity

jaw of steel

succinylcholine

Sch

propofol

malignant hyperthermia


Minor neurological dysfunction, cognitive development, and somatic development at the age of 3 to 7 years after dexamethasone treatment in very-low birth-weight infants.

The objective of this study was to assess minor neurological dysfunction, cognitive development, and somatic development after dexamethasone therapy in very-low-birthweight infants. Thirty-three children after dexamethasone treatment were matched to 33 children without dexamethasone treatment. Data were assessed at the age of 3-7 years. Dexamethasone was started between the 7th and the 28th day of life over 7 days with a total dose of 2.35 mg/kg/day. Exclusion criteria were asphyxia, malformations, major surgical interventions, small for gestational age, intraventricular haemorrhage grades III and IV, periventricular leukomalacia, and severe psychomotor retardation. Each child was examined by a neuropediatrician for minor neurological dysfunctions and tested by a psychologist for cognitive development with a Kaufman Assessment Battery for Children and a Draw-a-Man Test. There were no differences in demographic data, growth, and socio-economic status between the two groups. Fine motor skills and gross motor function were significantly better in the control group (p<0.01). In the Draw-a-Man Test, the control group showed better results (p<0.001). There were no differences in development of speech, social development, and the Kaufman Assessment Battery for Children. After dexamethasone treatment, children showed a higher rate of minor neurological dysfunctions. Neurological development was affected even without neurological diagnosis. Further long-term follow-up studies will be necessary to fully evaluate the impact of dexamethasone on neurological and cognitive development.

neurological dysfunction

dexamethasone

neurological dysfunction

dexamethasone

dexamethasone

dexamethasone

Dexamethasone

asphyxia

malformations

haemorrhage

periventricular leukomalacia

psychomotor retardation

neurological dysfunctions

dexamethasone

neurological dysfunctions

dexamethasone


Force overflow and levodopa-induced dyskinesias in Parkinson's disease.

We assessed force coordination of the hand in Parkinson's disease and its relationship to motor complications of levodopa therapy, particularly to levodopa-induced dyskinesias (LID). We studied two groups of Parkinson's disease patients with (Parkinson's disease + LID, n = 23) and without levodopa-induced dyskinesias (Parkinson's disease - LID, n = 10), and age-matched healthy controls. The motor score of the Unified Parkinson's Disease Rating Scale, a dyskinesia score and force in a grip-lift paradigm were assessed ON and OFF levodopa. A pathological increase of forces was seen in ON-state in Parkinson's disease + LID only. In Parkinson's disease + LID, the force involved in pressing down the object before lifting was significantly increased by levodopa (by 61%, P < 0.05). An overshooting of peak grip force by 51% (P < 0.05) and of static grip force by 45% (P < 0.01) was observed in the ON- compared with the OFF-drug condition. In contrast, no excessive force was found in Parkinson's disease - LID. Peak grip force in ON-state was 140% (P < 0.05) higher in Parkinson's disease + LID than in Parkinson's disease - LID, while static grip force was increased by 138% (P < 0.01) between groups. Severity of peak-dose dyskinesias was strongly correlated with grip force in ON-state (r = 0.79 with peak force, P < 0.01). No correlation was observed between forces and the motor score as well as with the daily dose of dopaminergic medication. Force excess was only observed in patients with LID and motor fluctuations. A close relationship was seen between the overshooting of forces and dyskinesias in the ON-drug condition. We postulate that both LID and grip force excess share common pathophysiological mechanisms related to motor fluctuations.

levodopa

dyskinesias

Parkinson's disease

Parkinson's disease

levodopa

levodopa

dyskinesias

LID

Parkinson's disease

Parkinson's disease

LID

levodopa

dyskinesias

Parkinson's disease

LID

Parkinson's Disease

dyskinesia

levodopa

Parkinson's disease

LID

Parkinson's disease

LID

levodopa

Parkinson's disease

LID

Parkinson's disease

LID

Parkinson's disease

LID

dyskinesias

LID

dyskinesias

LID


Postinfarction ventricular septal defect associated with long-term steroid therapy.

Two cases of postinfarction ventricular septal rupture in patients on long-term steroid therapy are presented and the favourable outcome in both cases described. A possible association between steroid therapy and subsequent postinfarction septal rupture is discussed.

ventricular septal defect

steroid

ventricular septal rupture

steroid

steroid

septal rupture


Angioedema associated with droperidol administration.

Angioedema, also known as angioneurotic edema or Quincke's disease, is a well-demarcated, localized edema involving the subcutaneous tissues that may cause upper-airway obstruction. We report the case of a previously healthy 19-year-old man with no known drug allergies in whom angioedema with significant tongue swelling and protrusion developed within 10 minutes of the administration of a single IV dose of droperidol.

Angioedema

droperidol

Angioedema

angioneurotic edema

Quincke's disease

edema

upper-airway obstruction

drug allergies

angioedema

tongue swelling

tongue swelling

swelling

droperidol


Clarithromycin-associated visual hallucinations in a patient with chronic renal failure on continuous ambulatory peritoneal dialysis.

Visual hallucinations are a rare event in chronic renal failure and not related to uremia per se. Unreported in the literature is visual hallucinations occurring in association with the new macrolide antibiotic, clarithromycin. We describe such a case in a patient with end-stage renal disease (ESRD) maintained on continuous ambulatory peritoneal dialysis (CAPD). The combination of a relatively high dose of clarithromycin in face of chronic renal failure in a functionally anephric patient, with underlying aluminum intoxication, may have facilitated the appearance of this neurotoxic side effect. It is important to understand the pharmacokinetics of medications in face of chronic renal failure, the possibility of drug interactions, and how these factors should help guide medication therapy in the ESRD patient.

Clarithromycin

visual hallucinations

chronic renal failure

Visual hallucinations

chronic renal failure

uremia

visual hallucinations

macrolide

clarithromycin

end-stage renal disease

ESRD

clarithromycin

chronic renal failure

aluminum

neurotoxic

chronic renal failure

ESRD


Acute renal toxicity of doxorubicin (adriamycin)-loaded cyanoacrylate nanoparticles.

Acute doxorubicin-loaded nanoparticle (DXNP) renal toxicity was explored in both normal rats and rats with experimental glomerulonephritis. In normal rats, 2/6 rats given free doxorubicin (DX) (5 mg/kg) died within one week, whereas all control animals and all rats having received free NP or DXNP survived. A 3 times higher proteinuria appeared in animals treated with DXNP than in those treated with DX. Free NP did not provoke any proteinuria. Two hr post-injection, DXNP was 2.7 times more concentrated in kidneys than free DX (p < 0.025). In rats with immune experimental glomerulonephritis, 5/6 rats given DX died within 7 days, in contrast to animals treated by DXNP, NP, or untreated, which all survived. Proteinuria appeared in all series, but was 2-5 times more intense (p > 0.001) and prolonged after doxorubicin treatment (400-700 mg/day), without significant difference between DXNP and DX. Rats treated by unloaded NP behaved as controls. These results demonstrate that, in these experimental conditions, DXNP killed less animals than free DX, despite of an enhanced renal toxicity of the former. Both effects (better survival and nephrosis) are most probably related to an enhanced capture of DXNP by cells of the mononuclear phagocyte system, including mesangial cells.

renal toxicity

doxorubicin

adriamycin

cyanoacrylate

doxorubicin

renal toxicity

glomerulonephritis

doxorubicin

DX

proteinuria

DX

proteinuria

DX

glomerulonephritis

DX

Proteinuria

doxorubicin

DX

DX

renal toxicity

nephrosis


Etoposide-related myocardial infarction.

The occurrence of a myocardial infarction is reported after chemotherapy containing etoposide, in a man with no risk factors for coronary heart disease. Possible causal mechanisms are discussed.

Etoposide

myocardial infarction

myocardial infarction

etoposide

coronary heart disease


Subjective assessment of sexual dysfunction of patients on long-term administration of digoxin.

Various data suggest that male patients who have received digoxin on a longterm basis have increased levels of serum estrogen and decreased levels of plasma testosterone and luteinizing hormone (LH). This study was undertaken to investigate the links between the long-term administration of digoxin therapy and sexual behavior, and the effect of digoxin on plasma levels of estradiol, testosterone, and LH. The patients of the study and control group (without digoxin) were of similar cardiac functional capacity and age (25-40 years) and were randomly selected from the rheumatic heart disease patients. A subjective assessment of sexual behavior in the study and control groups was carried out, using parameters such as sexual desire, sexual excitement, and frequency of sexual relations. Personal interviews and a questionnaire were also used for the evaluation of sexual behavior. The findings support the reports concerning digoxin effect on plasma estradiol, testosterone, and LH. The differences in the means were significant. Tests used to evaluate the changes in sexual behavior showed a significant decrease in sexual desire, sexual excitement phase (erection), and frequency of sexual relations in the study group.

sexual dysfunction

digoxin

digoxin

estrogen

testosterone

digoxin

digoxin

estradiol

testosterone

digoxin

rheumatic heart disease

digoxin

estradiol

testosterone

decrease in sexual desire


Fatal aplastic anemia due to indomethacin--lymphocyte transformation tests in vitro.

Although indomethacin has been implicated as a possible cause of aplastic anemia on the basis of a few clinical observations, its role has not been definitely established. A case of fatal aplastic anemia is described in which no drugs other than allopurinol and indomethacin were given. Indomethacin was first given four weeks prior to the onset of symptoms. A positive lymphocyte transformation test with indomethacin in vitro further substantiates the potential role of this drug in causing aplastic anemia in a susceptible patient. Fortunately, this seems to be a very rare complication.

aplastic anemia

indomethacin

indomethacin

aplastic anemia

aplastic anemia

allopurinol

indomethacin

Indomethacin

indomethacin

aplastic anemia


Plasma and urinary lipids and lipoproteins during the development of nephrotic syndrome induced in the rat by puromycin aminonucleoside.

This study was undertaken to ascertain whether the alterations of plasma lipoproteins found in nephrotic syndrome induced by puromycin aminonucleoside were due to nephrotic syndrome per se, or, at least in part, to the aminonucleoside. The purpose of the present study was to investigate the changes in plasma and urinary lipoproteins during the administration of puromycin aminonucleoside (20 mg/kg for 7 days) and the subsequent development of nephrotic syndrome. Since massive albuminuria occurred after 6 days of treatment, the time-course study was divided into two stages: pre-nephrotic stage (day 1-5) and nephrotic stage (day 6-11). In pre-nephrotic stage the plasma level of fatty acids, triacylglycerol and VLDL decreased while that of phospholipid, cholesteryl esters and HDL remained constant. Plasma apolipoprotein A-I tended to increase (40% increase at day 5). At the beginning of nephrotic stage (day 6) the concentration of plasma albumin dropped to a very low level, while that of apolipoprotein A-I increased abruptly (4-fold increase) and continued to rise, although less steeply, in the following days. The plasma concentration of HDL followed the same pattern. Plasma VLDL and LDL increased at a later stage (day 9). Plasma apolipoprotein A-I was found not only in HDL (1.063-1.210 g/ml) but also in the LDL density class (1.025-1.050 g/ml). In the pre-nephrotic stage lipoproteinuria was negligible, while in the early nephrotic stage the urinary loss of plasma lipoproteins consisted mainly of HDL. These observations indicate that puromycin aminonucleoside alters plasma lipoproteins by lowering VLDL and increasing HDL. It is likely that the early and striking increase of plasma HDL found in nephrotic rats is related to a direct effect of the drug on HDL metabolism.

nephrotic syndrome

puromycin aminonucleoside

nephrotic syndrome

puromycin aminonucleoside

nephrotic syndrome

aminonucleoside

puromycin aminonucleoside

nephrotic syndrome

albuminuria

nephrotic

nephrotic

nephrotic

fatty acids

triacylglycerol

cholesteryl esters

nephrotic

nephrotic

nephrotic

puromycin aminonucleoside

nephrotic


Circulating lysosomal enzymes and acute hepatic necrosis.

The activities of the lysosomal enzymes acid and neutral protease, N-acetylglucosaminidase, and acid phosphatase were measured in the serum of patients with fulminant hepatic failure. Acid protease (cathepsin D) activity was increased about tenfold in patients who died and nearly fourfold in those who survived fulminant hepatic failure after paracetamol overdose, whereas activities were increased equally in patients with fulminant hepatic failure due to viral hepatitis whether or not they survived. A correlation was found between serum acid protease activity and prothrombin time, and the increase in cathepsin D activity was sustained over several days compared with aspartate aminotransferase, which showed a sharp early peak and then a fall. Circulating lysosomal proteases can damage other organs, and measurement of their activity may therefore be of added value in assessing prognosis in this condition.

acute hepatic necrosis

fulminant hepatic failure

fulminant hepatic failure

paracetamol

overdose

fulminant hepatic failure

viral hepatitis

aspartate


Transketolase abnormality in tolazamide-induced Wernicke's encephalopathy.

We studied a thiamine-dependent enzyme, transketolase, from fibroblasts of a diabetic patient who developed Wernicke's encephalopathy when treated with tolazamide, in order to delineate if this patient also had transketolase abnormality [high Km for thiamine pyrophosphate (TPP)], as previously reported in postalcoholic Wernicke-Korsakoff syndrome. In addition to this patient, we also studied this enzyme from three diabetic kindreds without any history of Wernicke's encephalopathy and from four normal controls. We found that the above-mentioned patient and one of the diabetic kindreds with no history of Wernicke's encephalopathy had abnormal transketolase as determined by its Km for TPP. These data suggest a similarity between postalcoholic Wernicke-Korsakoff syndrome and the patient with tolazamide-induced Wernicke's encephalopathy from the standpoint of transketolase abnormality.

tolazamide

Wernicke's encephalopathy

thiamine

diabetic

Wernicke's encephalopathy

tolazamide

thiamine pyrophosphate

TPP

Wernicke-Korsakoff syndrome

diabetic

Wernicke's encephalopathy

diabetic

Wernicke's encephalopathy

TPP

Wernicke-Korsakoff syndrome

tolazamide

Wernicke's encephalopathy


Mechanisms of myocardial ischemia induced by epinephrine: comparison with exercise-induced ischemia.

The role of epinephrine in eliciting myocardial ischemia was examined in patients with coronary artery disease. Objective signs of ischemia and factors increasing myocardial oxygen consumption were compared during epinephrine infusion and supine bicycle exercise. Both epinephrine and exercise produced myocardial ischemia as evidenced by ST segment depression and angina. However, the mechanisms of myocardial ischemia induced by epinephrine were significantly different from those of exercise. Exercise-induced myocardial ischemia was marked predominantly by increased heart rate and rate-pressure product with a minor contribution of end-diastolic volume, while epinephrine-induced ischemia was characterized by a marked increase in contractility and a less pronounced increase in heart rate and rate-pressure product. These findings indicate that ischemia produced by epinephrine, as may occur during states of emotional distress, has a mechanism distinct from that due to physical exertion.

myocardial ischemia

epinephrine

ischemia

epinephrine

myocardial ischemia

coronary artery disease

ischemia

oxygen

epinephrine

epinephrine

myocardial ischemia

depression

angina

myocardial ischemia

epinephrine

myocardial ischemia

epinephrine

ischemia

ischemia

epinephrine


Transient contralateral rotation following unilateral substantia nigra lesion reflects susceptibility of the nigrostriatal system to exhaustion by amphetamine.

Following unilateral 6-OHDA induced SN lesion, a transient period of contralateral rotation has been reported to precede the predominant ipsilateral circling. In order to clarify the nature of this initial contralateral rotation we examined the effect of the duration of recovery period after the lesion, on amphetamine-induced rotational behavior. Three days post lesion, most rats circled predominantly contralaterally to the lesion. Such contralateral rotation may result from either degeneration-induced breakdown of the DA pool, or lesion-induced increase of DA turnover in the spared neurons. A substantial degree of contralateral preference was still evident when amphetamine was administered for the first time 24 days after lesioning, indicating involvement of spared cells in the contralateral rotation. However, regardless of the duration of recovery (and irrespective of either lesion volume, amphetamine dose, or post-lesion motor exercise), amphetamine-induced rotation tended to become gradually more ipsilateral as the observation session progressed, and all rats circled ipsilaterally to the lesion in response to further amphetamine injections. These findings suggest that amphetamine has an irreversible effect on the post-lesion DA pool contributing to contralateral rotation.

contralateral rotation

substantia nigra lesion

amphetamine

SN lesion

contralateral rotation

ipsilateral circling

contralateral rotation

amphetamine

rotational behavior

contralateral rotation

amphetamine

contralateral rotation

amphetamine

amphetamine

rotation

amphetamine

amphetamine

contralateral rotation


Thyroid function and urine-concentrating ability during lithium treatment.

It has been suggested that adenylate cyclase inhibition may be important in the development of both nephrogenic diabetes insipidus and hypothyroidism during lithium treatment. We measured serum thyroxine and urine-concentrating ability (Umax) in response to desmopressin (DDAVP) in 85 patients receiving lithium. Hypothyroidism developed in eight patients while they were taking lithium. Impaired Umax was found in both euthyroid and hypothyroid patients while some hypothyroid patients concentrated their urine well. It is concluded that the dominant mechanisms by which lithium exerts these two effects are different.

lithium

nephrogenic diabetes insipidus

hypothyroidism

lithium

thyroxine

lithium

Hypothyroidism

lithium

hypothyroid

hypothyroid

lithium


Sensitivity of erythroid progenitor colonies to erythropoietin in azidothymidine treated immunodeficient mice.

The anaemia induced by 3'-azido-3'dideoxythymidine (AZT) is poorly understood. We have used a murine model of AIDS, infection of female C57BL/6 mice with LP-BM5 murine leukaemia (MuLV) virus, to determine if AZT-induced anaemia is due, in part, to decreased responsiveness of erythropoietic precursors (BFU-e) to erythropoietin (EPO). Mice in the early stage of LP-BM5 MuLV disease were given AZT in their drinking water at 1.0 and 2.5 mg/ml. AZT produced anaemia in both groups, in a dose-dependent fashion. Despite the anaemia, the number of splenic and bone marrow BFU-e in AZT treated mice increased up to five-fold over levels observed in infected untreated animals after 15 d of treatment. Colony formation by splenic and bone marrow BFUe was stimulated at lower concentrations of EPO in mice receiving AZT for 15 d than for infected, untreated mice. By day 30, sensitivity of both splenic and bone marrow BFU-e of treated animals returned to that observed from cells of infected untreated animals. The mean plasma levels of EPO observed in AZT treated mice were appropriate for the degree of anaemia observed when compared with phenylhydrazine (PHZ) treated mice. The numbers of BFU-e and the percentage of bone marrow erythroblasts observed were comparable in AZT and PHZ treated mice with similar degrees of anaemia. However, reticulocytosis was inappropriate for the degree of anaemia observed in AZT treated infected mice. AZT-induced peripheral anaemia in the face of increased numbers of BFU-e and increased levels of plasma EPO suggest a lesion in terminal differentiation.

azidothymidine

immunodeficient

anaemia

AZT

AIDS

infection

leukaemia

AZT

anaemia

AZT

AZT

anaemia

anaemia

AZT

AZT

AZT

anaemia

phenylhydrazine

PHZ

AZT

PHZ

anaemia

reticulocytosis

anaemia

AZT

AZT

anaemia


Detection of abnormal cardiac adrenergic neuron activity in adriamycin-induced cardiomyopathy with iodine-125-metaiodobenzylguanidine.

Radiolabeled metaiodobenzylguanidine (MIBG), an analog of norepinephrine (NE), serves as an index of adrenergic neuron integrity and function. Using a rat model of adriamycin-induced cardiomyopathy, we tested the hypothesis that abnormal cardiac adrenergic neuron activity may appear and be exacerbated dose-dependently in adriamycin cardiomyopathy. The degree of vacuolar degeneration of myocardial cells was analyzed in relation to the duration of adriamycin treatment (2 mg/kg, once a week). There were no abnormalities or only isolated degeneration in the 1- or 2-wk treatment groups, isolated or scattered degeneration in half of the 3-wk group, frequent scattered degeneration in the 4-wk group, scattered or focal degeneration in the 5-wk group, and extensive degeneration in the 8-wk group. Myocardial accumulation of [125I]MIBG 4 hr after intravenous injection did not differ between the controls and the groups treated 3 wk or less. However, the 4-wk group had a slightly lower accumulation in the right ventricular wall (82% of the control) and significantly lower accumulation in the left ventricular wall (about 66% of the control: p less than 0.05). In the 5-wk group, MIBG accumulation in the right and left ventricular wall was 35% and 27% of that in controls, respectively (p less than 0.001). In the 8-wk group, MIBG accumulation in the right and left ventricular wall was 18% and 14% of that in controls, respectively (p less than 0.001). Thus, MIBG accumulation in the myocardium decreased in an adriamycin dose-dependent manner. The appearance of impaired cardiac adrenergic neuron activity in the presence of slight myocardial impairment (scattered or focal vacuolar degeneration) indicates that MIBG scintigraphy may be a useful method for detection of adriamycin-induced cardiomyopathy.

adriamycin

cardiomyopathy

Radiolabeled metaiodobenzylguanidine

MIBG

norepinephrine

NE

adriamycin

cardiomyopathy

adriamycin

cardiomyopathy

adriamycin

MIBG

MIBG

MIBG

MIBG

adriamycin

myocardial impairment

vacuolar degeneration

MIBG

adriamycin

cardiomyopathy


Amnestic syndrome associated with propranolol toxicity: a case report.

An elderly woman developed an Alzheimer-like subacute dementia as a result of propranolol toxicity. Analysis of the manifestations showed that severe impairment of memory accounted for virtually all of the abnormalities. There is evidence that cerebral reactions to drug toxicity can exhibit patterns that suggest highly selective involvement of functional subdivisions of the brain.

Amnestic syndrome

propranolol

toxicity

Alzheimer

dementia

propranolol

toxicity

toxicity


Biphasic response of the SA node of the dog heart in vivo to selective administration of ketamine.

Effect of ketamine on the SA node of the dog heart was studied in vivo using a selective perfusion technique of the SA node artery. Injections of ketamine in doses from 100 microgram to 3 mg into the artery produced a depression of the SA nodal activity by a direct action. This depression was followed by the sudden appearance of a stimulatory phase. Bilateral vagotomy and sympathectomy or prior administration of a ganglion blocker failed to inhibit the occurrence of the ketamine-induced tachycardia, while it was completely abolished in the reserpinized dogs or by a prior injection of a beta-blocking agent into the SA node artery. This may indicate that an activation of the peripheral adrenergic mechanism plays an important role in the induction of the excitatory effect of ketamine injected in the SA node artery.

ketamine

ketamine

ketamine

depression

depression

ketamine

tachycardia

ketamine


The use of serum cholinesterase in succinylcholine apnoea.

Fifteen patients demonstrating unexpected prolonged apnoea lasting several hours after succinylcholine have been treated by a new preparation of human serum cholinesterase. Adequate spontaneous respiration was re-established in an average period of ten minutes after the injection. In 12 patients biochemical genetic examinations confirmed the presence of an atypical serum cholinesterase. In three patients none of the usual variants were found. It is therefore supposed that other unknown variants of serum cholinesterase exist which cannot hydrolyze succinylcholine. The use of serum cholinesterase in succinylcholine apnoea provided considerable relief to both patient and anaesthetist.

succinylcholine

apnoea

apnoea

succinylcholine

succinylcholine

succinylcholine

apnoea


Orthostatic hypotension occurs following alpha 2-adrenoceptor blockade in chronic prazosin-pretreated conscious spontaneously hypertensive rats.

1. Studies were performed to evaluate whether chronic prazosin treatment alters the alpha 2-adrenoceptor function for orthostatic control of arterial blood pressure in conscious spontaneously hypertensive rats (SHR). 2. Conscious SHR (male 300-350 g) were subjected to 90 degrees head-up tilts for 60 s following acute administration of prazosin (0.1 mg kg-1 i.p.) or rauwolscine (3 mg kg-1 i.v.). Orthostatic hypotension was determined by the average decrease (%) in mean arterial pressure (MAP femoral) over the 60-s tilt period. The basal MAP of conscious SHR was reduced to a similar extent by prazosin (-23%(-)-26% MAP) and rauwolscine (-16%(-)-33% MAP). However, the head-up tilt induced orthostatic hypotension in the SHR treated with prazosin (-16% MAP, n = 6), but not in the SHR treated with rauwolscine (less than +2% MAP, n = 6). 3. Conscious SHR were treated for 4 days with prazosin at 2 mg kg-1 day-1 i.p. for chronic alpha 1-adrenoceptor blockade. MAP in conscious SHR after chronic prazosin treatment was 14% lower than in the untreated SHR (n = 8). Head-up tilts in these rats did not produce orthostatic hypotension when performed either prior to or after acute dosing of prazosin (0.1 mg kg-1 i.p.). Conversely, administration of rauwolscine (3 mg kg-1 i.v.) in chronic prazosin treated SHR decreased the basal MAP by 12-31% (n = 4), and subsequent tilts induced further drops of MAP by 19-23% in these rats. 4. The pressor responses and bradycardia to the alpha 1-agonist cirazoline (0.6 and 2 micrograms kg-1 i.v.), the alpha 2-agonist Abbott-53693 (1 and 3 micrograms kg-1 i.v.), and noradrenaline (0.1 and 1.0 micrograms kg-1 i.v.) were determined in conscious SHR with and without chronic prazosin pretreatment. Both the pressor and bradycardia effects of cirazoline were abolished in chronic prazosin treated SHR (n = 4) as compared to the untreated SHR (n = 4). On the other hand, the pressor effects of Abbott-53693 were similar in both groups of SHR, but the accompanying bradycardia was greater in SHR with chronic prazosin treatment than without such treatment. Furthermore, the bradycardia that accompanied the noradrenaline-induced pressor effect in SHR was similar with and without chronic prazosin treatment despite a 47-71% reduction of the pressor effect in chronic alpha 1-receptor blocked SHR.(ABSTRACT TRUNCATED AT 400 WORDS)

Orthostatic hypotension

prazosin

hypertensive

prazosin

hypertensive

prazosin

rauwolscine

Orthostatic hypotension

prazosin

rauwolscine

orthostatic hypotension

prazosin

rauwolscine

prazosin

prazosin

orthostatic hypotension

prazosin

rauwolscine

prazosin

bradycardia

cirazoline

noradrenaline

prazosin

bradycardia

cirazoline

prazosin

bradycardia

prazosin

bradycardia

noradrenaline

prazosin


Coexistence of cerebral venous sinus and internal carotid artery thrombosis associated with exogenous sex hormones. A case report.

A forty-six year-old premenopausal woman developed headache, nausea and vomiting, left hemiparesis and seizure two days after parenteral use of progesterone and estradiol. Diabetes mellitus (DM) was found during admission. Computed tomography showed a hemorrhagic infarct in the right frontal lobe and increased density in the superior sagittal sinus (SSS). Left carotid angiography found occlusion of the left internal carotid artery (ICA). Right carotid angiograms failed to show the SSS and inferior sagittal sinus, suggestive of venous sinus thrombosis. Coexistence of the cerebral artery and the venous sinus occlusion has been described infrequently. In this case, the authors postulate that the use of estradiol and progesterone and the underlying DM increased vascular thrombogenicity, which provided a common denominator for thrombosis of both the ICA and the venous sinus.

cerebral venous sinus
thrombosis

internal carotid artery thrombosis

headache

nausea

vomiting

hemiparesis

seizure

progesterone

estradiol

Diabetes mellitus

DM

hemorrhagic infarct

hemorrhagic

infarct

venous sinus thrombosis

cerebral artery
occlusion

the venous sinus occlusion

estradiol

progesterone

DM

thrombosis of
the ICA

thrombosis of
the venous sinus


Chloroquine related complete heart block with blindness: case report.

A 27-year old African woman with history of regular chloroquine ingestion presented with progressive deterioration of vision, easy fatiguability, dyspnoea, dizziness progressing to syncopal attacks. Ophthalmological assessment revealed features of chloroquine retinopathy, cardiac assessment revealed features of heart failure and a complete heart block with right bundle branch block pattern. The heart block was treated by pacemaker insertion and the heart failure resolved spontaneously following chloroquine discontinuation. She however remains blind.

Chloroquine

heart block

blindness

chloroquine

deterioration of vision

fatiguability

dyspnoea

dizziness

syncopal attacks

chloroquine

retinopathy

heart failure

heart block

right bundle branch block

heart block

heart failure

chloroquine

blind


Systemic toxicity and resuscitation in bupivacaine-, levobupivacaine-, or ropivacaine-infused rats.

We compared the systemic toxicity of bupivacaine, levobupivacaine, and ropivacaine in anesthetized rats. We also compared the ability to resuscitate rats after lethal doses of these local anesthetics. Bupivacaine, levobupivacaine, or ropivacaine was infused at a rate of 2 mg. kg(-1). min(-1) while electrocardiogram, electroencephalogram, and arterial pressure were continuously monitored. When asystole was recorded, drug infusion was stopped and a resuscitation sequence was begun. Epinephrine 0.01 mg/kg was administered at 1-min intervals while external cardiac compressions were applied. Resuscitation was considered successful when a systolic arterial pressure > or =100 mm Hg was achieved within 5 min. The cumulative doses of levobupivacaine and ropivacaine that produced seizures were similar and were larger than those of bupivacaine. The cumulative doses of levobupivacaine that produced dysrhythmias and asystole were smaller than the corresponding doses of ropivacaine, but they were larger than those of bupivacaine. The number of successful resuscitations did not differ among groups. However, a smaller dose of epinephrine was required in the Ropivacaine group than in the other groups. We conclude that the systemic toxicity of levobupivacaine is intermediate between that of ropivacaine and bupivacaine when administered at the same rate and that ropivacaine-induced cardiac arrest appears to be more susceptible to treatment than that induced by bupivacaine or levobupivacaine.

toxicity

bupivacaine

levobupivacaine

ropivacaine

toxicity

bupivacaine

levobupivacaine

ropivacaine

Bupivacaine

levobupivacaine

ropivacaine

asystole

Epinephrine

levobupivacaine

ropivacaine

seizures

bupivacaine

levobupivacaine

dysrhythmias

asystole

ropivacaine

bupivacaine

epinephrine

Ropivacaine

toxicity

levobupivacaine

ropivacaine

bupivacaine

ropivacaine

cardiac arrest

bupivacaine

levobupivacaine


22-oxacalcitriol suppresses secondary hyperparathyroidism without inducing low bone turnover in dogs with renal failure.

BACKGROUND: Calcitriol therapy suppresses serum levels of parathyroid hormone (PTH) in patients with renal failure but has several drawbacks, including hypercalcemia and/or marked suppression of bone turnover, which may lead to adynamic bone disease. A new vitamin D analogue, 22-oxacalcitriol (OCT), has been shown to have promising characteristics. This study was undertaken to determine the effects of OCT on serum PTH levels and bone turnover in states of normal or impaired renal function. METHODS: Sixty dogs were either nephrectomized (Nx, N = 38) or sham-operated (Sham, N = 22). The animals received supplemental phosphate to enhance PTH secretion. Fourteen weeks after the start of phosphate supplementation, half of the Nx and Sham dogs received doses of OCT (three times per week); the other half were given vehicle for 60 weeks. Thereafter, the treatment modalities for a subset of animals were crossed over for an additional eight months. Biochemical and hormonal indices of calcium and bone metabolism were measured throughout the study, and bone biopsies were done at baseline, 60 weeks after OCT or vehicle treatment, and at the end of the crossover period. RESULTS: In Nx dogs, OCT significantly decreased serum PTH levels soon after the induction of renal insufficiency. In long-standing secondary hyperparathyroidism, OCT (0.03 microg/kg) stabilized serum PTH levels during the first months. Serum PTH levels rose thereafter, but the rise was less pronounced compared with baseline than the rise seen in Nx control. These effects were accompanied by episodes of hypercalcemia and hyperphosphatemia. In animals with normal renal function, OCT induced a transient decrease in serum PTH levels at a dose of 0.1 microg/kg, which was not sustained with lowering of the doses. In Nx dogs, OCT reversed abnormal bone formation, such as woven osteoid and fibrosis, but did not significantly alter the level of bone turnover. In addition, OCT improved mineralization lag time, (that is, the rate at which osteoid mineralizes) in both Nx and Sham dogs. CONCLUSIONS: These results indicate that even though OCT does not completely prevent the occurrence of hypercalcemia in experimental dogs with renal insufficiency, it may be of use in the management of secondary hyperparathyroidism because it does not induce low bone turnover and, therefore, does not increase the risk of adynamic bone disease.

secondary hyperparathyroidism

low bone turnover

renal failure

Calcitriol

renal failure

hypercalcemia

suppression of bone turnover

adynamic bone disease

vitamin D

OCT

OCT

impaired renal function

phosphate

phosphate

OCT

calcium

OCT

OCT

renal insufficiency

secondary hyperparathyroidism

OCT

hypercalcemia

hyperphosphatemia

OCT

OCT

woven osteoid

fibrosis

OCT

OCT

hypercalcemia

renal insufficiency

secondary hyperparathyroidism

low bone turnover

adynamic bone disease


Chemotherapy of advanced inoperable non-small cell lung cancer with paclitaxel: a phase II trial.

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has demonstrated significant antineoplastic activity against different tumor types, notably ovarian and breast carcinoma. Two phase II trials of 24-hour paclitaxel infusions in chemotherapy-naive patients with stage IIIB or IV non-small cell lung cancer (NSCLC) reported response rates of 21% and 24%. Leukopenia was dose limiting: as many as 62.5% of patients experienced grade 4 leukopenia. We investigated the efficacy and toxicity of a 3-hour paclitaxel infusion in a phase II trial in patients with inoperable stage IIIB or IV NSCLC. The 58 patients treated (41 men and 17 women) had a median age of 59 years (age range, 25 to 75) and a performance status of 0 through 2. Most patients (72.4%) had stage IV NSCLC. Paclitaxel 225 mg/m2 was infused over 3 hours every 3 weeks with standard prophylactic premedication. Of 50 patients evaluable for response, 12 (24%) had partial remission, 26 (52%) had no change, and 12 had disease progression (24%). Hematologic toxicities were mild: only one patient (2%) developed grade 3 or 4 neutropenia, while 29% had grade 1 or 2. Grade 1 or 2 polyneuropathy affected 56% of patients while only one (2%) experienced severe polyneuropathy. Similarly, grade 1 or 2 myalgia/arthralgia was observed in 63.2% of patients, but only 14.3% experienced grade 3 or 4. Nausea and vomiting were infrequent, with 14% of patients experiencing grade 1 or 2 and only 2% experiencing grade 3 or 4. Paclitaxel is thus an active single agent in this patient population, with a 3-hour infusion proving comparably effective to a 24-hour infusion and superior in terms of the incidence of hematologic and nonhematologic toxicity. Further phase II studies with paclitaxel combined with other drugs active against NSCLC are indicated, and phase III studies comparing paclitaxel with standard chemotherapy remain to be completed.

non-small cell lung cancer

paclitaxel

Paclitaxel

Taxol

tumor

ovarian and breast carcinoma

ovarian carcinoma

breast carcinoma

paclitaxel

non-small cell lung cancer

NSCLC

Leukopenia

leukopenia

toxicity

paclitaxel

NSCLC

NSCLC

Paclitaxel

toxicities

neutropenia

polyneuropathy

polyneuropathy

myalgia

arthralgia

Nausea

vomiting

Paclitaxel

toxicity

paclitaxel

NSCLC

paclitaxel


Cerebral hemorrhage associated with phenylpropanolamine in combination with caffeine.

Phenylpropanolamine (PPA) is a drug that has been associated with serious side effects including stroke. It is often combined with caffeine in diet preparations and "look-alike" pills. In order to determine if PPA/caffeine can lead to stroke in normotensive and/or hypertensive rats, we administered the combination in six times the allowed human dose calculated on a per weight basis for the rats two times per day for five days. Subarachnoid and cerebral hemorrhage was noted in 18% of the hypertensive rats. A single PPA/caffeine administration (same dose) lead to acute hypertension in both the normotensive and hypertensive animals. These results suggest that PPA/caffeine can lead to cerebral hemorrhage in previously hypertensive animals when administered in greater than the allowed dosage. An acute elevation in blood pressure may be a contributing factor.

Cerebral hemorrhage

phenylpropanolamine

caffeine

Phenylpropanolamine

PPA

stroke

caffeine

PPA

caffeine

stroke

hypertensive

Subarachnoid and cerebral hemorrhage

Subarachnoid hemorrhage

cerebral hemorrhage

hypertensive

PPA

caffeine

hypertension

hypertensive

PPA

caffeine

cerebral hemorrhage

hypertensive


Long-term efficacy and toxicity of high-dose amiodarone therapy for ventricular tachycardia or ventricular fibrillation.

Amiodarone was administered to 154 patients who had sustained, symptomatic ventricular tachycardia (VT) (n = 118) or a cardiac arrest (n = 36) and who were refractory to conventional antiarrhythmic drugs. The loading dose was 800 mg/day for 6 weeks and the maintenance dose was 600 mg/day. Sixty-nine percent of patients continued treatment with amiodarone and had no recurrence of symptomatic VT or ventricular fibrillation (VF) over a follow-up of 6 to 52 months (mean +/- standard deviation 14.2 +/- 8.2). Six percent of the patients had a nonfatal recurrence of VT and were successfully managed by continuing amiodarone at a higher dose or by the addition of a conventional antiarrhythmic drug. One or more adverse drug reactions occurred in 51% of patients. Adverse effects forced a reduction in the dose of amiodarone in 41% and discontinuation of amiodarone in 10% of patients. The most common symptomatic adverse reactions were tremor or ataxia (35%), nausea and anorexia (8%), visual halos or blurring (6%), thyroid function abnormalities (6%) and pulmonary interstitial infiltrates (5%). Although large-dose amiodarone is highly effective in the long-term treatment of VT or VF refractory to conventional antiarrhythmic drugs, it causes significant toxicity in approximately 50% of patients. However, when the dose is adjusted based on clinical response or the development of adverse effects, 75% of patients with VT or VF can be successfully managed with amiodarone.

toxicity

amiodarone

ventricular tachycardia

ventricular fibrillation

Amiodarone

ventricular tachycardia

VT

cardiac arrest

amiodarone

VT

ventricular fibrillation

VF

VT

amiodarone

amiodarone

amiodarone

tremor

ataxia

nausea

anorexia

visual halos or blurring

thyroid function abnormalities

pulmonary interstitial infiltrates

amiodarone

VT

VF

toxicity

VT

VF

amiodarone


Effect of calcium chloride and 4-aminopyridine therapy on desipramine toxicity in rats.

BACKGROUND: Hypotension is a major contributor to mortality in tricyclic antidepressant overdose. Recent data suggest that tricyclic antidepressants inhibit calcium influx in some tissues. This study addressed the potential role of calcium channel blockade in tricyclic antidepressant-induced hypotension. METHODS: Two interventions were studied that have been shown previously to improve blood pressure with calcium channel blocker overdose. CaCl2 and 4-aminopyridine. Anesthetized rats received the tricyclic antidepressant desipramine IP to produce hypotension, QRS prolongation, and bradycardia. Fifteen min later, animals received CaCl2, NaHCO3, or saline. In a second experiment, rats received tricyclic antidepressant desipramine IP followed in 15 min by 4-aminopyridine or saline. RESULTS: NaHCO3 briefly (5 min) reversed hypotension and QRS prolongation. CaCl2 and 4-aminopyridine failed to improve blood pressure. The incidence of ventricular arrhythmias (p = 0.004) and seizures (p = 0.03) in the CaCl2 group was higher than the other groups. CONCLUSION: The administration of CaCl2 or 4-aminopyridine did not reverse tricyclic antidepressant-induced hypotension in rats. CaCl2 therapy may possibly worsen both cardiovascular and central nervous system toxicity. These findings do not support a role for calcium channel inhibition in the pathogenesis of tricyclic antidepressant-induced hypotension.

calcium chloride

desipramine

toxicity

Hypotension

overdose

calcium

calcium

hypotension

calcium

overdose

desipramine

hypotension

bradycardia

desipramine

hypotension

ventricular arrhythmias

seizures

hypotension

cardiovascular toxicity

central nervous system toxicity

calcium

hypotension


Phase I trial of 13-cis-retinoic acid in children with neuroblastoma following bone marrow transplantation.

PURPOSE: Treatment of neuroblastoma cell lines with 13-cis-retinoic acid (cis-RA) can cause sustained inhibition of proliferation. Since cis-RA has demonstrated clinical responses in neuroblastoma patients, it may be effective in preventing relapse after cytotoxic therapy. This phase I trial was designed to determine the maximal-tolerated dosage (MTD), toxicities, and pharmacokinetics of cis-RA administered on an intermittent schedule in children with neuroblastoma following bone marrow transplantation (BMT). PATIENTS AND METHODS: Fifty-one assessable patients, 2 to 12 years of age, were treated with oral cis-RA administered in two equally divided doses daily for 2 weeks, followed by a 2-week rest period, for up to 12 courses. The dose was escalated from 100 to 200 mg/m2/d until dose-limiting toxicity (DLT) was observed. A single intrapatient dose escalation was permitted. RESULTS: The MTD of cis-RA was 160 mg/m2/d. Dose-limiting toxicities in six of nine patients at 200 mg/m2/d included hypercalcemia (n = 3), rash (n = 2), and anemia/thrombocytopenia/emesis/rash (n = 1). All toxicities resolved after cis-RA was discontinued. Three complete responses were observed in marrow metastases. Serum levels of 7.4 +/- 3.0 mumol/L (peak) and 4.0 +/- 2.8 mumol/L (trough) at the MTD were maintained during 14 days of therapy. The DLT correlated with serum levels > or = 10 mumol/L. CONCLUSION: The MTD of cis-RA given on this intermittent schedule was 160 mg/m2/d. Serum levels known to be effective against neuroblastoma in vitro were achieved at this dose. The DLT included hypercalcemia, and may be predicted by serum cis-RA levels. Monitoring of serum calcium and cis-RA levels is indicated in future trials.

13-cis-retinoic acid

neuroblastoma

neuroblastoma

13-cis-retinoic acid

cis-RA

cis-RA

neuroblastoma

toxicities

cis-RA

neuroblastoma

cis-RA

toxicity

cis-RA

toxicities

hypercalcemia

rash

anemia

thrombocytopenia

emesis

rash

toxicities

cis-RA

metastases

cis-RA

neuroblastoma

hypercalcemia

cis-RA

calcium

cis-RA


Effect of calcium chloride on gross behavioural changes produced by carbachol and eserine in cats.

The effect of calcium chloride injected into the cerebral ventricles of group-housed unanaesthetized cats upon vocalization (rage, hissing and snarling), fighting (attack with paws and claws, defense with paws and claws and biting), mydriasis, tremor and clonic-tonic convulsions produced by carbachol and eserine injected similarly was investigated. Calcium chloride depressed or almost completely abolished the vocalization and fighting due to carbachol and eserine. On the other hand, mydriasis, tremor and clonic-tonic convulsions evoked by carbachol and eserine were not significantly changed by calcium chloride. It is apparent that calcium chloride can "dissociate" vocalization and fighting from autonomic and motor phenomena such as mydriasis, tremor and clonic-tonic convulsions caused by carbachol and eserine. Calcium chloride inhibited the vocalization and fighting produced by carbachol and eserine most probably by a nonspecific stabilizing action on central muscarinic cholinoceptive sites. These results further support the view that calcium ions in excess have an atropine-like action also in the central nervous system.

calcium chloride

carbachol

eserine

calcium chloride

mydriasis

tremor

clonic-tonic convulsions

carbachol

eserine

Calcium chloride

carbachol

eserine

mydriasis

tremor

clonic-tonic convulsions

carbachol

eserine

calcium chloride

calcium chloride

mydriasis

tremor

clonic-tonic convulsions

carbachol

eserine

Calcium chloride

carbachol

eserine

calcium

atropine


Multiple side effects of penicillamine therapy in one patient with rheumatoid arthritis.

Skin rashes, proteinuria, systemic lupus erythematosus, polymyositis and myasthenia gravis have all been recorded as complications of penicillamine therapy in patients with rheumatoid arthritis. A patient who had developed all 5 is now described. The skin lesion resembled elastosis perforans serpiginosa, which has been reported as a rare side effect in patients with Wilson's disease but not in patients with rheumatoid arthritis treated with penicillamine.

penicillamine

rheumatoid arthritis

Skin rashes

proteinuria

systemic lupus erythematosus

polymyositis

myasthenia gravis

penicillamine

rheumatoid arthritis

skin lesion

elastosis perforans serpiginosa

Wilson's disease

rheumatoid arthritis

penicillamine


Electrocardiographic changes and cardiac arrhythmias in patients receiving psychotropic drugs.

Eight patients had cardiac manifestations that were life-threatening in five while taking psychotropic drugs, either phenothiazines or tricyclic antidepressants. Although most patients were receiving several drugs, Mellaril (thioridazine) appeared to be responsible for five cases of ventricular tachycardia, one of which was fatal in a 35 year old woman. Supraventricular tachycardia developed in one patient receiving Thorazine (chlorpromazine). Aventyl (nortriptyline) and Elavil (amitriptyline) each produced left bundle branch block in a 73 year old woman. Electrocardiographic T and U wave abnormalities were present in most patients. The ventricular arrhythmias responded to intravenous administration of lidocaine and to direct current electric shock; ventricular pacing was required in some instances and intravenous administration of propranolol combined with ventricular pacing in one. The tachyarrhythmias generally subsided within 48 hours after administration of the drugs was stopped. Five of the eight patients were 50 years of age or younger; only one clearly had antecedent heart disease. Major cardiac arrhythmias are a potential hazard in patients without heart disease who are receiving customary therapeutic doses of psychotropic drugs. A prospective clinical trial is suggested to quantify the risk of cardiac complications to patients receiving phenothiazines or tricyclic antidepressant drugs.

cardiac arrhythmias

phenothiazines

Mellaril

thioridazine

ventricular tachycardia

Supraventricular tachycardia

Thorazine

chlorpromazine

Aventyl

nortriptyline

Elavil

amitriptyline

left bundle branch block

ventricular arrhythmias

lidocaine

propranolol

tachyarrhythmias

heart disease

cardiac arrhythmias

heart disease

cardiac complications

phenothiazines


Serotonergic drugs, benzodiazepines and baclofen block muscimol-induced myoclonic jerks in a strain of mice.

In male Swiss mice, muscimol produced myoclonic jerks. A 3 mg/kg (i.p.) dose induced this response in all of the mice tested and the peak response of 73 jerks per min was observed between 27 and 45 min. Increasing the brain serotonin levels by the administration of 5-hydroxytryptophan (80-160 mg/kg) in combination with a peripheral decarboxylase inhibitor resulted in an inhibition of the muscimol effect. However, in a similar experiment l-dopa (80-160 mg/kg) was without effect. In doses of 3-10 mg/kg, the serotonin receptor agonist MK-212 caused a dose-dependent blockade of the response of muscimol. Of the benzodiazepines, clonazepam (0.1-0.3 mg/kg) was found to be several fold more potent than diazepam (0.3-3 mg/kg) in blocking the myoclonic jerks. While (-)-baclofen (1-3 mg/kg) proved to be an effective antagonist of muscimol, its (+)-isomer (5-20 mg/kg) lacked this property. Considering the fact that 5-HTP and the benzodiazepines have been found to be beneficial in the management of clinical myoclonus, the muscimol-induced myoclonus seems to be a satisfactory animal model that may prove useful for the development of new drug treatments for this condition. Our present study indicated the possible value of MK-212 and (-)-baclofen in the management of clinical myoclonus.

benzodiazepines

baclofen

muscimol

myoclonic jerks

muscimol

myoclonic jerks

serotonin

muscimol

l-dopa

serotonin

muscimol

benzodiazepines

clonazepam

diazepam

myoclonic jerks

baclofen

muscimol

benzodiazepines

myoclonus

muscimol

myoclonus

baclofen

myoclonus


Hyperglycemic acidotic coma and death in Kearns-Sayre syndrome.

This paper presents the clinical and metabolic findings in two young boys with long-standing Kearns-Sayre syndrome. Following short exposure to oral prednisone, both boys developed lethargy, increasing somnolence, polydipsia, polyphagia, and polyuria. Both presented in the emergency room with profound coma, hypotension, severe hyperglycemia, and acidosis. Nonketotic lactic acidosis was present in one and ketosis without a known serum lactate level was present in the other. Respiratory failure rapidly ensued and both patients expired in spite of efforts at resuscitation. We believe these two cases represent a newly described and catastrophic metabolic-endocrine failure in the Kearns-Sayre syndrome.

Hyperglycemic acidotic coma

Hyperglycemic

acidotic

coma

Kearns-Sayre syndrome

Kearns-Sayre syndrome

prednisone

lethargy

somnolence

polydipsia

polyphagia

polyuria

coma

hypotension

hyperglycemia

acidosis

lactic acidosis

ketosis

lactate

Respiratory failure

metabolic-endocrine failure

Kearns-Sayre syndrome


Effects of active constituents of Crocus sativus L., crocin on streptozocin-induced model of sporadic Alzheimer's disease in male rats.

BACKGROUND: The involvement of water-soluble carotenoids, crocins, as the main and active components of Crocus sativus L. extract in learning and memory processes has been proposed. In the present study, the effect of crocins on sporadic Alzheimer's disease induced by intracerebroventricular (icv) streptozocin (STZ) in male rats was investigated. METHODS: Male adult Wistar rats (n = 90 and 260-290 g) were divided into 1, control; 2 and 3, crocins (15 and 30 mg/kg); 4, STZ; 5 and 6, STZ + crocins (15 and 30 mg/kg) groups. In Alzheimer's disease groups, rats were injected with STZ-icv bilaterally (3 mg/kg) in first day and 3 days later, a similar STZ-icv application was repeated. In STZ + crocin animal groups, crocin was applied in doses of 15 and 30 mg/kg, i.p., one day pre-surgery and continued for three weeks. Prescription of crocin in each dose was repeated once for two days. However, the learning and memory performance was assessed using passive avoidance paradigm, and for spatial cognition evaluation, Y-maze task was used. RESULTS: It was found out that crocin (30 mg/kg)-treated STZ-injected rats show higher correct choices and lower errors in Y-maze than vehicle-treated STZ-injected rats. In addition, crocin in the mentioned dose could significantly attenuated learning and memory impairment in treated STZ-injected group in passive avoidance test. CONCLUSION: Therefore, these results demonstrate the effectiveness of crocin (30 mg/kg) in antagonizing the cognitive deficits caused by STZ-icv in rats and its potential in the treatment of neurodegenerative diseases such as Alzheimer's disease.

crocin

streptozocin

Alzheimer's disease

carotenoids

crocins

crocins

Alzheimer's disease

streptozocin

STZ

crocins

STZ

STZ

crocins

Alzheimer's disease

STZ

STZ

STZ

crocin

crocin

crocin

crocin

STZ

STZ

crocin

learning and memory impairment

learning impairment

memory impairment

STZ

crocin

cognitive deficits

STZ

neurodegenerative diseases

Alzheimer's disease


Rosaceiform dermatitis associated with topical tacrolimus treatment.

We describe herein 3 patients who developed rosacea-like dermatitis eruptions while using 0.03% or 0.1% tacrolimus ointment for facial dermatitis. Skin biopsy specimens showed telangiectasia and noncaseating epithelioid granulomatous tissue formation in the papillary to mid dermis. Continuous topical use of immunomodulators such as tacrolimus or pimecrolimus should be regarded as a potential cause of rosaceiform dermatitis, although many cases have not been reported.

dermatitis

tacrolimus

rosacea

dermatitis

eruptions

tacrolimus

facial dermatitis

telangiectasia

tacrolimus

pimecrolimus

dermatitis


A novel animal model to evaluate the ability of a drug delivery system to promote the passage through the BBB.

The purpose of this investigation was to explore the potentiality of a novel animal model to be used for the in vivo evaluation of the ability of a drug delivery system to promote the passage through the blood-brain barrier (BBB) and/or to improve the brain localization of a bioactive compound. A Tween 80-coated poly-L-lactid acid nanoparticles was used as a model of colloidal drug delivery system, able to trespass the BBB. Tacrine, administered in LiCl pre-treated rats, induces electrocorticographic seizures and delayed hippocampal damage. The toxic effects of tacrine-loaded poly-L-lactid acid nanoparticles (5mg/kg), a saline solution of tacrine (5mg/kg) and an empty colloidal nanoparticle suspension were compared following i.p. administration in LiCl-pre-treated Wistar rats. All the animals treated with tacrine-loaded nanoparticles showed an earlier outcome of CNS adverse symptoms, i.e. epileptic onset, with respect to those animals treated with the free compound (10 min vs. 22 min respectively). In addition, tacrine-loaded nanoparticles administration induced damage of neuronal cells in CA1 field of the hippocampus in all treated animals, while the saline solution of tacrine only in 60% of animals. Empty nanoparticles provided similar results to control (saline-treated) group of animals. In conclusion, the evaluation of time-to-onset of symptoms and the severity of neurodegenerative processes induced by the tacrine-lithium model of epilepsy in the rat, could be used to evaluate preliminarily the capability of a drug delivery system to trespass (or not) the BBB in vivo.

poly-L-lactid acid

Tacrine

LiCl

seizures

hippocampal damage

tacrine

poly-L-lactid acid

tacrine

LiCl

tacrine

epileptic

tacrine

damage of neuronal cells

tacrine

tacrine

lithium

epilepsy


The antiarrhythmic effect and possible ionic mechanisms of pilocarpine on animal models.

This study was designed to evaluate the effects of pilocarpine and explore the underlying ionic mechanism, using both aconitine-induced rat and ouabain-induced guinea pig arrhythmia models. Confocal microscopy was used to measure intracellular free-calcium concentrations ([Ca(2+)](i)) in isolated myocytes. The current data showed that pilocarpine significantly delayed onset of arrhythmias, decreased the time course of ventricular tachycardia and fibrillation, reduced arrhythmia score, and increased the survival time of arrhythmic rats and guinea pigs. [Ca(2+)](i) overload induced by aconitine or ouabain was reduced in isolated myocytes pretreated with pilocarpine. Moreover, M(3)-muscarinic acetylcholine receptor (mAChR) antagonist 4-DAMP (4-diphenylacetoxy-N-methylpiperidine-methiodide) partially abolished the beneficial effects of pilocarpine. These data suggest that pilocarpine produced antiarrhythmic actions on arrhythmic rat and guinea pig models induced by aconitine or ouabain via stimulating the cardiac M(3)-mAChR. The mechanism may be related to the improvement of Ca(2+) handling.

pilocarpine

pilocarpine

aconitine

ouabain

arrhythmia

calcium

Ca

pilocarpine

arrhythmias

ventricular tachycardia

ventricular fibrillation

arrhythmia

arrhythmic

Ca

aconitine

ouabain

pilocarpine

acetylcholine

pilocarpine

pilocarpine

arrhythmic

aconitine

ouabain

Ca


Disulfiram-induced transient optic and peripheral neuropathy: a case report.

AIM: To report a case of optic and peripheral neuropathy after chronic use of disulfiram for alcohol dependence management. MATERIALS AND METHODS: A case report. RESULTS: A 57-year-old male presented with gradual loss of vision in both eyes with intermittent headaches for 2 months. He also complained of paraesthesia with numbness in both feet. His vision was 6/15 and 2/60 in the right and left eyes, respectively. Fundoscopy revealed bilaterally swollen optic nerve heads. Visual field testing confirmed bilateral central-caecal scotomata. He had been taking disulfiram for alcohol dependence for the preceding 3 years. Disulfiram discontinuation lead to an immediate symptomatic improvement. CONCLUSION: Physicians initiating long-term disulfiram therapy should be aware of these adverse effects. They should recommend annual ophthalmic reviews with visual field testing. Patients should be reassured with respect to the reversibility of these adverse effects.

Disulfiram

optic and peripheral neuropathy

optic neuropathy

peripheral neuropathy

optic and peripheral neuropathy

optic neuropathy

peripheral neuropathy

disulfiram

alcohol dependence

loss of vision

headaches

paraesthesia

numbness

scotomata

disulfiram

alcohol dependence

Disulfiram

disulfiram


Sustained clinical improvement of a patient with decompensated hepatitis B virus-related cirrhosis after treatment with lamivudine monotherapy.

Hepatitis B virus (HBV) infection, which causes liver cirrhosis and hepatocellular carcinoma, remains a major health problem in Asian countries. Recent development of vaccine for prevention is reported to be successful in reducing the size of chronically infected carriers, although the standard medical therapies have not been established up to now. In this report, we encountered a patient with decompensated HBV-related cirrhosis who exhibited the dramatic improvements after antiviral therapy. The patient was a 50-year-old woman. Previous conventional medical treatments were not effective for this patient, thus this patient had been referred to our hospital. However, the administration of lamivudine, a reverse transcriptase inhibitor, for 23 months dramatically improved her liver severity. During this period, no drug resistant mutant HBV emerged, and the serum HBV-DNA level was continuously suppressed. These virological responses were also maintained even after the antiviral therapy was discontinued. Moreover, both hepatitis B surface antigen and e antigen were observed to have disappeared in this patient. The administration of lamivudine to patients with HBV-related cirrhosis, like our present case, should be considered as an initial medical therapeutic option, especially in countries where liver transplantation is not reliably available.

hepatitis B

cirrhosis

lamivudine

Hepatitis B virus (HBV) infection

liver cirrhosis

hepatocellular carcinoma

cirrhosis

lamivudine

hepatitis B surface antigen

hepatitis B
e antigen

lamivudine

cirrhosis


Dual effects of melatonin on barbiturate-induced narcosis in rats.

Melatonin affects the circadian sleep/wake cycle, but it is not clear whether it may influence drug-induced narcosis. Sodium thiopenthal was administered intraperitoneally into male rats pre-treated with melatonin (0.05, 0.5, 5 and 50 mg/kg). Melatonin pre-treatment affected in a dual manner barbiturate narcosis, however, no dose-effect correlation was found. In particular, low doses reduced the latency to and prolonged the duration of barbiturate narcosis. In contrast, the highest dose of melatonin (50 mg/kg) caused a paradoxical increase in the latency and produced a sustained reduction of the duration of narcosis, and a reduction in mortality rate. Melatonin 0.5 and 5 mg/kg influenced the duration but not the latency of ketamine- or diazepam-induced narcosis. Thus, the dual action of melatonin on pharmacological narcosis seems to be specific for the barbiturate mechanism of action.

melatonin

barbiturate

narcosis

Melatonin

narcosis

Sodium thiopenthal

melatonin

Melatonin

barbiturate

narcosis

barbiturate

narcosis

melatonin

narcosis

Melatonin

ketamine

diazepam

narcosis

melatonin

narcosis

barbiturate


Effects of NIK-247 on cholinesterase and scopolamine-induced amnesia.

The effects of NIK-247 on cholinesterase, scopolamine-induced amnesia and spontaneous movement were examined and compared with those of the well-known cholinesterase inhibitors tacrine and E-2020. NIK-247, tacrine and E-2020 all strongly inhibited acetylcholinesterase (AChE) in human red blood cells (IC50s = 1.0 x 10(-6), 2.9 x 10(-7) and 3.7 x 10(-8) M, respectively). In addition, NIK-247 and tacrine, but not E-2020, strongly inhibited butyrylcholinestrase (BuChE) in human serum. All three drugs produced mixed inhibition of AChE activity. Moreover, the inhibitory effect of NIK-247 on AChE was reversible. All compounds at 0.1-1 mg/kg p.o. significantly improved the amnesia induced by scopolamine (0.5 mg/kg s.c.) in rats performing a passive avoidance task. The three compounds at 1 and 3 mg/kg p.o. did not significantly decrease spontaneous movement by rats. These findings suggest that NIK-247 at a low dose (0.1-1 mg/kg p.o.) improves scopolamine-induced amnesia but does not affect spontaneous movement. The findings suggest that NIK-247 may be a useful drug for the treatment of Alzheimer's disease.

scopolamine

amnesia

scopolamine

amnesia

tacrine

tacrine

tacrine

amnesia

scopolamine

scopolamine

amnesia

Alzheimer's disease


Nightmares and hallucinations after long-term intake of tramadol combined with antidepressants.

Tramadol is a weak opioid with effects on adrenergic and serotonergic neurotransmission that is used to treat cancer pain and chronic non malignant pain. This drug was initiated in association with paroxetine and dosulepine hydrochloride in a tetraparetic patient with chronic pain. Fifty-six days after initiation of the treatment the patient presented hallucinations that only stopped after the withdrawal of psycho-active drugs and tramadol. The case report questions the long term use of pain killers combined with psycho-active drugs in chronic non malignant pain, especially if pain is under control.

hallucinations

tramadol

Tramadol

cancer

pain

pain

paroxetine

dosulepine hydrochloride

tetraparetic

chronic pain

hallucinations

tramadol

pain

pain

pain


Apparent cure of rheumatoid arthritis by bone marrow transplantation.

We describe the induction of sustained remissions and possible cure of severe erosive rheumatoid arthritis (RA) by bone marrow transplantation (BMT) in 2 patients. BMT was used to treat severe aplastic anemia which was caused by gold in one case and D-penicillamine in the other. In the 8 and 6 years since the transplants (representing 8 and 4 years since cessation of all immunosuppressive therapy, respectively), the RA in each case has been completely quiescent. Although short term remission of severe RA following BMT has been reported, these are the first cases for which prolonged followup has been available. This experience raises the question of the role of BMT itself as a therapeutic option for patients with uncontrolled destructive synovitis.

rheumatoid arthritis

rheumatoid arthritis

RA

aplastic anemia

gold

D-penicillamine

RA

RA

synovitis


Urinary enzymes and protein patterns as indicators of injury to different regions of the kidney.

Acute experimental models of renal damage to the proximal tubular, glomerular, and papillary regions of the rat were produced by administration of hexachloro-1:3-butadiene (HCBD), puromycin aminonucleoside (PAN), and 2-bromoethylamine (BEA), respectively. Several routine indicators of nephrotoxicity, the enzymes alkaline phosphatase and N-acetyl-beta-glucosaminidase, and the molecular weight of protein excretion were determined on urine samples. Tubular damage produced by HCBD or BEA was discriminated both quantitatively and qualitatively from glomerular damage produced by PAN. The latter was characterized by a pronounced increase in protein excretion, especially proteins with molecular weight greater than 40,000 Da. In contrast, protein excretion in tubular damage was raised only slightly and characterized by excretion of proteins of a wide range of molecular weights. Proximal tubular damage caused by HCBD and papillary damage caused by BEA were distinguished both by conventional urinalysis (volume and specific gravity) and by measurement of the two urinary enzymes. Alkaline phosphatase and glucose were markedly and transiently elevated in proximal tubular damage and N-acetyl-beta-glucosaminidase showed a sustained elevation in papillary damage. It is concluded that both selective urinary enzymes and the molecular weight pattern of urinary proteins can be used to provide diagnostic information about the possible site of renal damage.

HCBD

puromycin aminonucleoside

PAN

BEA

nephrotoxicity

protein excretion

HCBD

BEA

glomerular damage

PAN

protein excretion

protein excretion

excretion of proteins

HCBD

BEA

glucose

renal damage


Neuromuscular blockade with magnesium sulfate and nifedipine.

A patient who received tocolysis with nifedipine developed neuromuscular blockade after 500 mg of magnesium sulfate was administered. This reaction demonstrates that nifedipine can seriously potentiate the toxicity of magnesium. Caution should be exercised when these two tocolytics are combined.

Neuromuscular blockade

magnesium sulfate

nifedipine

nifedipine

neuromuscular blockade

magnesium sulfate

nifedipine

toxicity

magnesium


Ifosfamide continuous infusion without mesna. A phase I trial of a 14-day cycle.

Twenty patients received 27 courses of ifosfamide administered as a 24-hour continuous infusion for 14 days without Mesna. The goal of the study was to deliver a dose rate and total cumulative dose of ifosfamide that would be comparable to standard bolus or short-term infusions administered with Mesna. Dose escalations proceeded from 200 to 300, 400, 450, 500, and 550 mg/m2/d. Four patients developed transient microscopic hematuria at 400, 450, and 500 mg/m2/d. There were no instances of macroscopic hematuria. At 550 mg/m2/d, three patients experienced nonurologic toxicity; confusion (1), nausea (1), and Grade 2 leukopenia (1). The recommended dose of 500 mg/m2/d delivers a total dose of 7 g/m2 per cycle, which is comparable to that delivered in clinical practice for bolus or short-term infusion. Because few patients received multiple courses over time, the cumulative effects are indeterminate in the present trial. The frequency and predictability of hematuria are not precise, and at least daily monitoring by urine Hematest is essential, adding Mesna to the infusate in patients with persistent hematuria. The protracted infusion schedule for ifosfamide permits convenient outpatient administration without Mesna and reduces the drug cost of clinical usage of this agent by up to  890 per cycle. Clinical activity was demonstrated in a single patient, but a comparative trial of standard bolus schedules with the protracted infusion schedule will be necessary to determine if the clinical effectiveness of the drug is maintained.

Ifosfamide

mesna

ifosfamide

Mesna

ifosfamide

Mesna

hematuria

hematuria

toxicity

confusion

nausea

leukopenia

hematuria

Mesna

hematuria

ifosfamide

Mesna


Myocardial infarction in pregnancy associated with clomiphene citrate for ovulation induction: a case report.

BACKGROUND: Clomiphene citrate (CC) is commonly prescribed for ovulation induction. It is considered safe, with minimal side effects. Thromboembolism is a rare but life-threatening complication that has been reported after ovulation induction with CC. Spontaneous coronary thrombosis or thromboembolism with subsequent clot lysis has been suggested as one of the most common causes of myocardial infarction (MI) during pregnancy, with a subsequently normal coronary angiogram. CASE: A 33-year-old woman with a 5-week gestation had recently received CC for ovulation induction and presented with chest pain. An electrocardiogram showed a lateral and anterior wall myocardial infarction. Cardiac enzymes showed a peak rise in troponin I to 9.10 ng/mL. An initial exercise stress test was normal. At the time of admission, the patient was at high risk of radiation injury to the fetus, so a coronary angiogram was postponed until the second trimester. It showed normal coronary vessels. CONCLUSION: This appears to be the first reported case documenting a possible association between CC and myocardial infarction. Thrombosis might be a rare but hazardous complication of CC. Given this life-threatening complication, appropriate prophylactic measures should be used in high-risk woman undergoing ovarian stimulation.

Myocardial infarction

clomiphene citrate

Clomiphene citrate

CC

Thromboembolism

CC

coronary thrombosis

thromboembolism

myocardial infarction

MI

CC

chest pain

myocardial infarction

radiation injury

CC

myocardial infarction

Thrombosis

CC


Hepatonecrosis and cholangitis related to long-term phenobarbital therapy: an autopsy report of two patients.

Phenobarbital (PB) has a reputation for safety, and it is commonly believed that PB-related increases in serum aminotransferase levels do not indicate or predict the development of significant chronic liver disease. Here we report of two adult patients with a long history of epilepsy treated with PB who died suddenly: one as consequence of cardiac arrest, the other of acute bronchopneumonia. At autopsy, analysis of liver parenchyma revealed rich portal inflammatory infiltrate, which consisted of mixed eosinophil and monocyte cells, associated with several foci of necrosis surrounded by a hard ring of non-specific granulomatous tissue. Inflammatory reactions of internal and external hepatic biliary ducts were also seen. Our findings illustrate that PB may be associated with chronic liver damage, which may lead to more serious and deleterious consequences. For this reason, each clinician should recognize this entity in the differential diagnosis of PB-related asymptomatic chronic hepatic enzyme dysfunction.

Hepatonecrosis

cholangitis

phenobarbital

Phenobarbital

PB

PB

liver disease

epilepsy

PB

cardiac arrest

bronchopneumonia

necrosis

PB

liver damage

PB

chronic hepatic enzyme dysfunction


Ethambutol-associated optic neuropathy.

INTRODUCTION: Ethambutol is used in the treatment of tuberculosis, which is still prevalent in Southeast Asia, and can be associated with permanent visual loss. We report 3 cases which presented with bitemporal hemianopia. CLINICAL PICTURE: Three patients with ethambutol-associated toxic optic neuropathy are described. All 3 patients had loss of central visual acuity, colour vision (Ishihara) and visual field. The visual field loss had a bitemporal flavour, suggesting involvement of the optic chiasm. TREATMENT: Despite stopping ethambutol on diagnosis, visual function continued to deteriorate for a few months. Subsequent improvement was mild in 2 cases. In the third case, visual acuity and colour vision normalised but the optic discs were pale. OUTCOME: All 3 patients had some permanent loss of visual function. CONCLUSIONS: Ethambutol usage is associated with permanent visual loss and should be avoided if possible or used with caution and proper ophthalmological follow-up. The author postulates that in cases of ethambutol associated chiasmopathy, ethambutol may initially affect the optic nerves and subsequently progress to involve the optic chiasm.

Ethambutol

optic neuropathy

Ethambutol

tuberculosis

visual loss

bitemporal hemianopia

ethambutol

optic neuropathy

visual field loss

ethambutol

loss of visual function

Ethambutol

visual loss

ethambutol

ethambutol


Tolerability of nimesulide and paracetamol in patients with NSAID-induced urticaria/angioedema.

Previous studies evaluated the tolerance of nimesulide and paracetamol in subjects with cutaneous, respiratory and anaphylactoid reactions induced by nonsteroidal anti-inflammatory drugs (NSAIDs). In this study we investigated tolerability and reliability of nimesulide and paracetamol in a very large number of patients with an exclusive well-documented history of NSAID-induced urticaria/angioedema. Furthermore, we evaluated whether some factors have the potential to increase the risk of reaction to paracetamol and nimesulide. A single-placebo-controlled oral challenge procedure with nimesulide or paracetamol was applied to 829 patients with a history of NSAID-induced urticaria/angioedema. A total of 75/829 (9.4%) patients experienced reactions to nimesulide or paracetamol. Of the 715 patients tested with nimesulide 62 (8.6%) showed a positive test, while of 114 subjects submitted to the challenge with paracetamol, 13 (9.6%) did not tolerate this drug. Furthermore, 18.28% of patients with a history of chronic urticaria and 11.8% of subjects with an history of NSAID-induced urticaria/angioedema or angioedema alone (with or without chronic urticaria) resulted to be intolerant to alternative drugs. Taken together, our results confirm the good tolerability of nimesulide and paracetamol in patients who experienced urticaria/angioedema caused by NSAIDs. However, the risk of reaction to these alternative study drugs is statistically increased by a history of chronic urticaria and, above all, by a history of NSAID-induced angioedema.

nimesulide

paracetamol

NSAID

urticaria

angioedema

nimesulide

paracetamol

nonsteroidal anti-inflammatory drugs

NSAIDs

nimesulide

paracetamol

NSAID

urticaria

angioedema

paracetamol

nimesulide

nimesulide

paracetamol

NSAID

urticaria

angioedema

nimesulide

paracetamol

nimesulide

paracetamol

urticaria

NSAID

urticaria

angioedema

angioedema

urticaria

nimesulide

paracetamol

urticaria

angioedema

NSAIDs

urticaria

NSAID

angioedema