Toxicity due to remission inducing drugs in rheumatoid arthritis. Association with HLA-B35 and Cw4 antigens.

Twenty-five patients with rheumatoid arthritis (RA) who developed toxicity while taking remission inducing drugs and 30 without toxicity were studied for possible associations with class I and II HLA antigens. A strong association has been found between nephritis and dermatitis due to Tiopronin (a D-Penicillamine like compound) and class I antigens B35-Cw4, and between dermatitis due to gold thiosulphate and B35. Compared to healthy controls a lower DR5 frequency was observed in patients with RA except for the Tiopronin related nephritis group.

Toxicity

rheumatoid arthritis

rheumatoid arthritis

RA

toxicity

toxicity

nephritis

dermatitis

Tiopronin

D-Penicillamine

dermatitis

gold

thiosulphate

RA

Tiopronin

nephritis


Transient hemiparesis: a rare manifestation of diphenylhydantoin toxicity. Report of two cases.

Among the common side effects of diphenylhydantoin (DPH) overdose, the most frequently encountered neurological signs are those of cerebellar dysfunction. Very rarely, the toxic neurological manifestations of this drug are of cerebral origin. Two patients are presented who suffered progressive hemiparesis due to DPH overdose. Both had brain surgery before DPH treatment. It is assumed that patients with some cerebral damage are liable to manifest DPH toxicity as focal neurological signs.

hemiparesis

diphenylhydantoin

toxicity

diphenylhydantoin

DPH

overdose

cerebellar dysfunction

hemiparesis

DPH

overdose

DPH

cerebral damage

DPH

toxicity


Nerve growth factor and prostaglandins in the urine of female patients with overactive bladder.

PURPOSE: NGF and PGs in the bladder can be affected by pathological changes in the bladder and these changes can be detected in urine. We investigated changes in urinary NGF and PGs in women with OAB. MATERIALS AND METHODS: The study groups included 65 women with OAB and 20 without bladder symptoms who served as controls. Evaluation included patient history, urinalysis, a voiding diary and urodynamic studies. Urine samples were collected. NGF, PGE2, PGF2alpha and PGI2 were measured using enzyme-linked immunosorbent assay and compared between the groups. In addition, correlations between urinary NGF and PG, and urodynamic parameters in patients with OAB were examined. RESULTS: Urinary NGF, PGE2 and PGF2alpha were significantly increased in patients with OAB compared with controls (p <0.05). However, urinary PGI2 was not different between controls and patients with OAB. In patients with OAB urinary PGE2 positively correlated with volume at first desire to void and maximum cystometric capacity (p <0.05). Urinary NGF, PGF2alpha and PGI2 did not correlate with urodynamic parameters in patients with OAB. CONCLUSIONS: NGF and PGs have important roles in the development of OAB symptoms in female patients. Urinary levels of these factors may be used as markers to evaluate OAB symptoms.

prostaglandins

overactive bladder

PGs

PGs

OAB

OAB

PG

OAB

OAB

OAB

OAB

OAB

PGs

OAB

OAB


Acute low back pain during intravenous administration of amiodarone: a report of two cases.

Amiodarone represents an effective antiarrhythmic drug for cardioversion of recent-onset atrial fibrillation (AF) and maintenance of sinus rhythm. We briefly describe two patients suffering from recent-onset atrial fibrillation, who experienced an acute devastating low back pain a few minutes after initiation of intravenous amiodarone loading. Notably, this side effect has not been ever reported in the medical literature. Clinicians should be aware of this reaction since prompt termination of parenteral administration leads to complete resolution.

low back pain

amiodarone

Amiodarone

atrial fibrillation

AF

atrial fibrillation

low back pain

amiodarone


Postoperative myalgia after succinylcholine: no evidence for an inflammatory origin.

A common side effect associated with succinylcholine is postoperative myalgia. The pathogenesis of this myalgia is still unclear; inflammation has been suggested but without convincing evidence. We designed the present study to investigate whether an inflammatory reaction contributes to this myalgia. The incidence and severity of succinylcholine-associated myalgia was determined in 64 patients pretreated with saline or dexamethasone before succinylcholine (n = 32 for each). Incidence and severity of myalgia did not differ significantly between the two groups: 15 patients in the dexamethasone group complained of myalgia compared with 18 patients in the saline group, and severe myalgia was reported by five patients and three patients, respectively (not significant). At 48 h after surgery, 12 patients in both groups still suffered from myalgia (not significant). In addition, interleukin-6 (IL-6) as an early marker of inflammation was assessed in a subgroup of 10 patients pretreated with saline. We found an increase of IL-6 for only three patients, but only one patient reported myalgia; no relationship between myalgia and the increase of IL-6 was found. In conclusion, there is no evidence for an inflammatory origin of succinylcholine-associated myalgia. IMPLICATIONS: Administration of dexamethasone before succinylcholine was not effective in decreasing the incidence or the severity of succinylcholine-induced postoperative myalgia. Furthermore, there was no significant relationship between postoperative myalgia and time course of interleukin-6 concentrations, a marker of inflammation. Pretreatment with dexamethasone is not justified to prevent postoperative myalgia after succinylcholine.

Postoperative myalgia

succinylcholine

succinylcholine

postoperative myalgia

myalgia

inflammation

myalgia

succinylcholine

myalgia

dexamethasone

succinylcholine

myalgia

dexamethasone

myalgia

myalgia

myalgia

inflammation

myalgia

myalgia

succinylcholine

myalgia

dexamethasone

succinylcholine

succinylcholine

postoperative myalgia

postoperative myalgia

inflammation

dexamethasone

postoperative myalgia

succinylcholine


Levodopa-induced oromandibular dystonia in progressive supranuclear palsy.

Levodopa-induced dyskinesias have been reported in Parkinson's disease and multiple system atrophy. Cranial dystonias are rare in patients with progressive supranuclear palsy (PSP). In this report we describe an unusual case of reversible levodopa-induced Oromandibular dystonia (OMD) in a PSP patient to highlight the importance of recognizing this drug related complication in the management of PSP, and discuss the possible underlying pathophysiology.

Levodopa

dystonia

progressive supranuclear palsy

Levodopa

dyskinesias

Parkinson's disease

multiple system atrophy

dystonias

progressive supranuclear palsy

PSP

levodopa

Oromandibular dystonia

OMD

PSP

PSP


Protective effect of edaravone against streptomycin-induced vestibulotoxicity in the guinea pig.

This study investigated alleviation of streptomycin-induced vestibulotoxicity by edaravone in guinea pigs. Edaravone, a free radical scavenger, has potent free radical quenching action and is used in clinical practice to treat cerebral infarction. Streptomycin was administered to the inner ear by osmotic pump for 24 h, and edaravone (n=8) or saline (n=6) was intraperitoneally injected once a day for 7 days. We observed horizontal vestibulo-ocular reflex as a marker of postoperative vestibular function. Animals injected with saline showed statistically smaller gains than those injected with edaravone. These results suggest that edaravone suppresses streptomycin-induced vestibulotoxicity.

edaravone

streptomycin

vestibulotoxicity

streptomycin

vestibulotoxicity

edaravone

Edaravone

cerebral infarction

Streptomycin

edaravone

edaravone

edaravone

streptomycin

vestibulotoxicity


Ketamine in war/tropical surgery (a final tribute to the racemic mixture).

A technique of continuous intravenous anaesthesia with ketamine was used successfully during the Somalia civil war in 1994 and in north Uganda in 1999 for 64 operations in 62 patients, aged from 6 weeks to 70 years, undergoing limb and abdominal surgery including caesarian sections and interventions in neonates. Operations lasting up to 2h could be performed in the absence of sophisticated equipment such as pulse oximeters or ventilators in patients on spontaneous ventilation breathing air/oxygen only. After premedication with diazepam, glycopyrrolate and local anaesthesia, and induction with standard doses of ketamine, a maintenance dose of 10-20 microg/kg/min of ketamine proved safe and effective. Emphasis was placed on bedside clinical monitoring, relying heavily on the heart rate. Diazepam, unless contraindicated or risky, remains the only necessary complementary drug to ketamine as it buffers its cardiovascular response and decreases the duration and intensity of operative and postoperative hallucinations. Local anaesthetic blocks were useful in decreasing the requirement for postoperative analgesia. An antisialogue was usually unnecessary in operations lasting up to 2 h, glycopyrrolate being the best choice for its lowest psychotropic and chronotropic effects, especially in a hot climate. Experience in war/tropical settings suggests this technique could be useful in civilian contexts such as outdoor life-saving emergency surgery or in mass casualties where, e.g. amputation and rapid extrication were required.

Ketamine

ketamine

oxygen

diazepam

glycopyrrolate

ketamine

ketamine

Diazepam

ketamine

hallucinations

analgesia

glycopyrrolate


Steroid structure and pharmacological properties determine the anti-amnesic effects of pregnenolone sulphate in the passive avoidance task in rats.

Pregnenolone sulphate (PREGS) has generated interest as one of the most potent memory-enhancing neurosteroids to be examined in rodent learning studies, with particular importance in the ageing process. The mechanism by which this endogenous steroid enhances memory formation is hypothesized to involve actions on glutamatergic and GABAergic systems. This hypothesis stems from findings that PREGS is a potent positive modulator of N-methyl-d-aspartate receptors (NMDARs) and a negative modulator of gamma-aminobutyric acid(A) receptors (GABA(A)Rs). Moreover, PREGS is able to reverse the amnesic-like effects of NMDAR and GABA(A)R ligands. To investigate this hypothesis, the present study in rats examined the memory-altering abilities of structural analogs of PREGS, which differ in their modulation of NMDAR and/or GABA(A)R function. The analogs tested were: 11-ketopregnenolone sulphate (an agent that is inactive at GABA(A)Rs and NMDARs), epipregnanolone ([3beta-hydroxy-5beta-pregnan-20-one] sulphate, an inhibitor of both GABA(A)Rs and NMDARs), and a newly synthesized (-) PREGS enantiomer (which is identical to PREGS in effects on GABA(A)Rs and NMDARs). The memory-enhancing effects of PREGS and its analogs were tested in the passive avoidance task using the model of scopolamine-induced amnesia. Both PREGS and its (-) enantiomer blocked the effects of scopolamine. The results show that, unlike PREGS, 11-ketopregnenolone sulphate and epipregnanolone sulphate failed to block the effect of scopolamine, suggesting that altering the modulation of NMDA receptors diminishes the memory-enhancing effects of PREGS. Moreover, enantioselectivity was demonstrated by the ability of natural PREGS to be an order of magnitude more effective than its synthetic enantiomer in reversing scopolamine-induced amnesia. These results identify a novel neuropharmacological site for the modulation of memory processes by neuroactive steroids.

Steroid

amnesic

pregnenolone sulphate

Pregnenolone sulphate

PREGS

steroid

PREGS

N-methyl-d-aspartate

gamma-aminobutyric acid

GABA

PREGS

amnesic

GABA

PREGS

GABA

11-ketopregnenolone sulphate

GABA

GABA

PREGS

PREGS

GABA

PREGS

scopolamine

amnesia

PREGS

scopolamine

PREGS

11-ketopregnenolone sulphate

epipregnanolone sulphate

scopolamine

NMDA

PREGS

PREGS

scopolamine

amnesia

steroids


Preliminary efficacy assessment of intrathecal injection of an American formulation of adenosine in humans.

BACKGROUND: Preclinical studies of intrathecal adenosine suggest it may be effective in the treatment of acute and chronic pain in humans, and preliminary studies in volunteers and patients with a Swedish formulation of adenosine suggests it may be effective in hypersensitivity states but not with acute noxious stimulation. The purpose of this study was to screen for efficacy of a different formulation of adenosine marketed in the US, using both acute noxious stimulation and capsaicin-evoked mechanical hypersensitivity. METHODS: Following Food and Drug Administration and institutional review board approval and written informed consent, 65 volunteers were studied in two trials: an open-label, dose-escalating trial with intrathecal adenosine doses of 0.25-2.0 mg and a double-blind, placebo-controlled trial of adenosine, 2 mg. Cerebrospinal fluid was obtained for pharmacokinetic analysis, and pain ratings in response to acute heat stimuli and areas of mechanical hyperalgesia and allodynia after intradermal capsaicin injection were determined. RESULTS: Adenosine produced no effect on pain report to acute noxious thermal or chemical stimulation but reduced mechanical hyperalgesia and allodynia from intradermal capsaicin injection for at least 24 h. In contrast, residence time of adenosine in cerebrospinal fluid was short (< 4 h). CONCLUSIONS: These results show selective inhibition by intrathecal adenosine of hypersensitivity, presumed to reflect central sensitization in humans after peripheral capsaicin injection. The long-lasting effect is consistent with that observed in preliminary reports of patients with chronic neuropathic pain and is not due to prolonged residence of adenosine in cerebrospinal fluid.

adenosine

adenosine

acute and chronic pain

acute pain

chronic pain

adenosine

hypersensitivity

adenosine

capsaicin

hypersensitivity

adenosine

adenosine

pain

mechanical hyperalgesia

allodynia

capsaicin

Adenosine

pain

mechanical hyperalgesia

allodynia

capsaicin

adenosine

adenosine

hypersensitivity

capsaicin

neuropathic pain

adenosine


Effect of lithium maintenance therapy on thyroid and parathyroid function.

OBJECTIVES: To assess changes induced by lithium maintenance therapy on the incidence of thyroid, parathyroid and ion alterations. These were evaluated with respect to the duration of lithium therapy, age, sex, and family history (whether or not the patient had a first-degree relative with thyroid disease). DESIGN: Prospective study. SETTING: Affective Disorders Clinic at St. Mary's Hospital, Montreal. PATIENTS: One hundred and one patients (28 men and 73 women) with bipolar disorder receiving lithium maintenance therapy ranging from 1 year's to 32 years' duration. The control group consisted of 82 patients with no psychiatric or endocrinological diagnoses from the hospital's out-patient clinics. OUTCOME MEASURES: Laboratory analyses of calcium, magnesium and thyroid-stimulating hormone levels performed before beginning lithium therapy and at biannual follow-up. RESULTS: Hypothyroidism developed in 40 patients, excluding 8 patients who were hypothyroid at baseline. All patients having first-degree relatives affected by thyroid illness had accelerated onset of hypothyroidism (3.7 years after onset of lithium therapy) compared with patients without a family history (8.6 years after onset of lithium therapy). Women over 60 years of age were more often affected by hypothyroidism than women under 60 years of age (34.6% versus 31.9%). Magnesium levels in patients on lithium treatment were unchanged from baseline levels. After lithium treatment, calcium levels were higher than either baseline levels or control levels. Thus, lithium treatment counteracted the decrease in plasma calcium levels associated with aging. CONCLUSIONS: Familial thyroid illness is a risk factor for hypothyroidism and hypercalcemia during lithium therapy.

lithium

lithium

lithium

thyroid disease

bipolar disorder

lithium

psychiatric

calcium

magnesium

lithium

Hypothyroidism

hypothyroid

thyroid illness

hypothyroidism

lithium

lithium

hypothyroidism

Magnesium

lithium

lithium

calcium

lithium

calcium

thyroid illness

hypothyroidism

hypercalcemia

lithium


Systemic toxicity following administration of sirolimus (formerly rapamycin) for psoriasis: association of capillary leak syndrome with apoptosis of lesional lymphocytes.

BACKGROUND: Sirolimus (formerly rapamycin) is an immunosuppressive agent that interferes with T-cell activation. After 2 individuals with psoriasis developed a capillary leak syndrome following treatment with oral sirolimus lesional skin cells and activated peripheral blood cells were analyzed for induction of apoptosis. OBSERVATIONS: A keratome skin specimen from 1 patient with sirolimus-induced capillary leak syndrome had a 2.3-fold increase in percentage of apoptotic cells (to 48%) compared with an unaffected sirolimus-treated patient with psoriasis (21%). Activated peripheral blood T cells from patients with psoriasis tended to exhibit greater spontaneous or dexamethasone-induced apoptosis than did normal T cells, particularly in the presence of sirolimus. CONCLUSIONS: Severe adverse effects of sirolimus include fever, anemia, and capillary leak syndrome. These symptoms may be the result of drug-induced apoptosis of lesional leukocytes, especially activated T lymphocytes, and possibly release of inflammatory mediators. Because patients with severe psoriasis may develop capillary leak from various systemic therapies, clinical monitoring is advisable for patients with inflammatory diseases who are treated with immune modulators.

toxicity

sirolimus

rapamycin

psoriasis

capillary leak syndrome

Sirolimus

rapamycin

psoriasis

capillary leak syndrome

sirolimus

sirolimus

capillary leak syndrome

sirolimus

psoriasis

psoriasis

dexamethasone

sirolimus

sirolimus

fever

anemia

capillary leak syndrome

psoriasis

capillary leak

inflammatory diseases


Contribution of the glycine site of NMDA receptors in rostral and intermediate-caudal parts of the striatum to the regulation of muscle tone in rats.

The aim of the present study was to assess the contribution of the glycine site of NMDA receptors in the striatum to the regulation of muscle tone. Muscle tone was examined using a combined mechanoand electromyographic method, which measured simultaneously the muscle resistance (MMG) of the rat's hind foot to passive extension and flexion in the ankle joint and the electromyographic activity (EMG) of the antagonistic muscles of that joint: gastrocnemius and tibialis anterior. Muscle rigidity was induced by haloperidol (2.5 mg/kg i.p.). 5,7-dichlorokynurenic acid (5,7-DCKA), a selective glycine site antagonist, injected in doses of 2.5 and 4.5 microg/0.5 microl bilaterally, into the rostral region of the striatum, decreased both the haloperidol-induced muscle rigidity (MMG) and the enhanced electromyographic activity (EMG). 5,7-DCKA injected bilaterally in a dose of 4.5 microg/0.5 microl into the intermediate-caudal region of the striatum of rats not pretreated with haloperidol had no effect on the muscle tone. The present results suggest that blockade of the glycine site of NMDA receptors in the rostral part of the striatum may be mainly responsible for the antiparkinsonian action of this drug.

glycine

NMDA

glycine

NMDA

Muscle rigidity

haloperidol

5,7-dichlorokynurenic acid

glycine

haloperidol

muscle rigidity

haloperidol

glycine

NMDA


Efficacy and tolerability of lovastatin in 3390 women with moderate hypercholesterolemia.

OBJECTIVE: To evaluate the efficacy and safety of lovastatin in women with moderate hypercholesterolemia. DESIGN: The Expanded Clinical Evaluation of Lovastatin (EXCEL) Study, a multicenter, double-blind, diet- and placebo-controlled trial, in which participants were randomly assigned to receive placebo or lovastatin at doses of 20 or 40 mg once daily, or 20 or 40 mg twice daily for 48 weeks. SETTING: Ambulatory patients recruited by 362 participating centers throughout the United States. PATIENTS: Women (n = 3390) from the total cohort of 8245 volunteers. MEASUREMENTS: Plasma total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol, and triglycerides; and laboratory and clinical evidence of adverse events monitored periodically throughout the study. RESULTS: Among women, lovastatin (20 to 80 mg/d) produced sustained (12- to 48-week), dose-related changes (P < 0.001): decreases in LDL cholesterol (24% to 40%) and triglycerides (9% to 18%), and increases in HDL cholesterol (6.7% to 8.6%). Depending on the dose, from 82% to 95% of lovastatin-treated women achieved the National Cholesterol Education Program goal of LDL cholesterol levels less than 4.14 mmol/L (160 mg/dL), and 40% to 87% achieved the goal of 3.36 mmol/L (130 mg/dL). Successive transaminase elevations greater than three times the upper limit of normal occurred in 0.1% of women and were dose dependent above the 20-mg dose. Myopathy, defined as muscle symptoms with creatine kinase elevations greater than 10 times the upper limit of normal, was rare and associated with the highest recommended daily dose of lovastatin (80 mg). Estrogen-replacement therapy appeared to have no effect on either the efficacy or safety profile of lovastatin. CONCLUSION: Lovastatin is highly effective and generally well tolerated as therapy for primary hypercholesterolemia in women.

lovastatin

hypercholesterolemia

lovastatin

hypercholesterolemia

Lovastatin

lovastatin

cholesterol

triglycerides

lovastatin

cholesterol

triglycerides

cholesterol

lovastatin

Cholesterol

cholesterol

Myopathy

creatine

lovastatin

lovastatin

Lovastatin

hypercholesterolemia


REM sleep deprivation changes behavioral response to catecholaminergic and serotonergic receptor activation in rats.

The effects of REM sleep deprivation (REMD) on apomorphine-induced aggressiveness and quipazine-induced head twitches in rats were determined. Forty-eight hr of REMD increased apomorphine-induced aggressiveness, and reduced (immediately after completing of REMD) or increased (96 hr after completing of REMD) quipazine-induced head twitches. Results are discussed in terms of similarity to pharmacological effects of other antidepressive treatments.

REM sleep deprivation

REM sleep deprivation

REMD

apomorphine

aggressiveness

quipazine

head twitches

REMD

apomorphine

aggressiveness

REMD

REMD

quipazine

head twitches


Extrapyramidal side effects and oral haloperidol: an analysis of explanatory patient and treatment characteristics.

The incidence of extrapyramidal side effects (EPS) was evaluated in 98 patients treated with haloperidol. The incidence of parkinsonism was higher at higher doses of haloperidol and in younger patients. Prophylactic antiparkinsonian medication was effective in younger but not in older patients. However, these medications were more effective in both young and old patients when given after parkinsonism developed. Akathisia was controlled by the benzodiazepine lorazepam in 14 out of 16 patients, while prophylactic antiparkinsonians were ineffective. The present study points to patient characteristics that may be of significance in the development of EPS due to haloperidol.

haloperidol

haloperidol

parkinsonism

haloperidol

parkinsonism

Akathisia

benzodiazepine

lorazepam

haloperidol


Hepatic veno-occlusive disease caused by 6-thioguanine.

Clinically reversible veno-occlusive disease of the liver developed in a 23-year-old man with acute lymphocytic leukemia after 10 months of maintenance therapy with 6-thioguanine. Serial liver biopsies showed the development and resolution of intense sinusoidal engorgement. Although this disease was clinically reversible, some subintimal fibrosis about the terminal hepatic veins persisted. This case presented a unique opportunity to observe the histologic features of clinically reversible hepatic veno-occlusive disease over time, and may be the first case of veno-occlusive related solely to 6-thioguanine.

Hepatic veno-occlusive disease

veno-occlusive disease of the liver

acute lymphocytic leukemia

fibrosis

hepatic veno-occlusive disease


Treatment of ifosfamide-induced urothelial toxicity by oral administration of sodium 2-mercaptoethane sulphonate (MESNA) to patients with inoperable lung cancer.

The protective effect of oral administration of the thiol compound sodium 2-mercaptoethane sulphonate (MESNA) against urothelial toxicity induced by ifosfamide (IF) was tested in a group of 45 patients with inoperable lung cancer under treatment with IF (2250 mg/m2 on days 2-5) as part of a polychemotherapy regimen repeated in a 4-week cycle. MESNA was given orally on the days of treatment with IF in 3 doses of 840 mg/m2, each administered at 0 hr (= injection of IF), 4 hr and 8 hr p.i. Out of a total of 88 courses of this treatment we observed 10 episodes of asymptomatic microscopic haematuria and no episodes of gross haematuria. In this group of 45 patients under protection with MESNA there were 5 complete remissions and 9 partial remissions (total 31%). A further group of 25 patients under polychemotherapy with IF were treated by conventional prophylactic measures (raised fluid intake and forced diuresis). In this group there were 1 complete and 5 partial remissions (total 24%), but nearly all patients developed either gross haematuria and/or symptoms of bladder irritation (cystitis and pollakisuria). There were no appreciable differences between the MESNA series and the conventional prophylaxis series with respect to either haematological or systemic toxicity of the cytostatic treatment. Our results support the view that MESNA, given orally in conjunction with combined cytostatic regimens which include IF, simplifies the treatment and provides optimum protection for the urinary epithelium. Protection with oral MESNA is particularly suitable for outpatients.

ifosfamide

urothelial toxicity

sodium 2-mercaptoethane sulphonate

MESNA

lung cancer

thiol

sodium 2-mercaptoethane sulphonate

MESNA

urothelial toxicity

ifosfamide

IF

lung cancer

IF

MESNA

IF

IF

haematuria

haematuria

MESNA

IF

haematuria

bladder irritation

cystitis

pollakisuria

MESNA

toxicity

MESNA

IF

MESNA


Time course alterations of QTC interval due to hypaque 76.

Sequential measurement of QT interval during left ventricular angiography was made 30 seconds and one, three, five and ten minutes after injection of hypaque 76. The subjects were ten patients found to have normal left ventricles and coronary arteries. Significant QTC prolongation occurred in 30 seconds to one minute in association with marked hypotension and elevation of cardiac output.

hypaque 76

hypaque 76

QTC prolongation

hypotension


Production of autochthonous prostate cancer in Lobund-Wistar rats by treatments with N-nitroso-N-methylurea and testosterone.

More than 50% of Lobund-Wistar (L-W) strain rats developed large, palpable prostate adenocarcinomas (PAs) following treatments with N-nitroso-N-methylurea (CAS: 684-93-5) and testosterone propionate [(TP) CAS: 57-85-2], and most of the tumor-bearing rats manifested metastatic lesions. The incubation periods averaged 10.6 months. Within the same timeframe, no L-W rat developed a similar palpable PA when treated only with TP. In L-W rats, TP acted as a tumor enhancement agent, with primary emphasis on the development of prostate cancer.

prostate cancer

N-nitroso-N-methylurea

testosterone

prostate adenocarcinomas

PAs

N-nitroso-N-methylurea

testosterone propionate

TP

tumor

PA

TP

TP

tumor

prostate cancer


A dystonia-like syndrome after neuropeptide (MSH/ACTH) stimulation of the rat locus ceruleus.

The movement disorder investigated in these studies has some features in common with human idiopathic dystonia, and information obtained in these studies may be of potential clinical benefit. The present experimental results indicated that peptidergic stimulation of the LC resulted in a NE-mediated inhibition of cerebellar Purkinje cells located at terminals of the ceruleo-cerebellar pathway. However, it is not certain as to the following: (a) what receptors were stimulated by the ACTH N-terminal fragments at the LC that resulted in this disorder; (b) whether NE, released onto Purkinje cell synapses located at terminals of the ceruleo-cerebellar pathway, did indeed cause the long-term depression at Purkinje cell synapses (previously described by others) that resulted in the long duration of the movement disorder; (c) whether the inhibition of inhibitory Purkinje cells resulted in disinhibition or increased excitability of the unilateral cerebellar fastigial or interpositus nuclei, the output targets of the Purkinje cell axons, that may have been an important contributing factor to this disorder. These questions are currently being investigated.

dystonia

MSH

ACTH

movement disorder

dystonia

ACTH

depression

movement disorder


Dexmedetomidine, acting through central alpha-2 adrenoceptors, prevents opiate-induced muscle rigidity in the rat.

The highly-selective alpha-2 adrenergic agonist dexmedetomidine (D-MED) is capable of inducing muscle flaccidity and anesthesia in rats and dogs. Intense generalized muscle rigidity is an undesirable side effect of potent opiate agonists. Although the neurochemistry of opiate-induced rigidity has yet to be fully elucidated, recent work suggests a role for a central adrenergic mechanism. In the present study, the authors determined if treatment with D-MED prevents the muscle rigidity caused by high-dose alfentanil anesthesia in the rat. Animals (n = 42) were treated intraperitoneally with one of the following six regimens: 1) L-MED (the inactive L-isomer of medetomidine), 30 micrograms/kg; 2) D-MED, 10 micrograms/kg; 3) D-MED, 30 micrograms/kg; 4) D-MED [30 micrograms/kg] and the central-acting alpha-2 antagonist, idazoxan [10 mg/kg]; 5) D-MED [30 micrograms/kg] and the peripheral-acting alpha-2 antagonist DG-5128 [10 mg/kg], or; 6) saline. Baseline electromyographic activity was recorded from the gastrocnemius muscle before and after drug treatment. Each rat was then injected with alfentanil (ALF, 0.5 mg/kg sc). ALF injection resulted in a marked increase in hindlimb EMG activity in the L-MED treatment group which was indistinguishable from that seen in animals treated with saline. In contrast, D-MED prevented alfentanil-induced muscle rigidity in a dose-dependent fashion. The small EMG values obtained in the high-dose D-MED group were comparable with those recorded in earlier studies from control animals not given any opiate. The high-dose D-MED animals were flaccid, akinetic, and lacked a startle response during the entire experimental period.(ABSTRACT TRUNCATED AT 250 WORDS)

Dexmedetomidine

muscle rigidity

dexmedetomidine

D-MED

muscle flaccidity

muscle rigidity

rigidity

D-MED

muscle rigidity

alfentanil

medetomidine

D-MED

D-MED

D-MED

idazoxan

D-MED

alfentanil

ALF

ALF

D-MED

alfentanil

muscle rigidity

D-MED

D-MED

akinetic

startle


Seizure activity with imipenem therapy: incidence and risk factors.

Two elderly patients with a history of either cerebral vascular accident (CVA) or head trauma and no evidence of renal disease developed seizures while receiving maximum doses of imipenem/cilastatin. Neither patient had reported previous seizures or seizure-like activity nor was receiving anticonvulsant agents. All seizures were controlled with therapeutic doses of phenytoin. Both patients had received maximum doses of other beta-lactam antibiotics without evidence of seizure activity.

Seizure

imipenem

cerebral vascular accident

CVA

head trauma

renal disease

seizures

imipenem/cilastatin

seizures

seizure

seizures

phenytoin

beta-lactam

seizure


The ability of insulin treatment to reverse or prevent the changes in urinary bladder function caused by streptozotocin-induced diabetes mellitus.

1. The effects of insulin treatment on in vivo and in vitro urinary bladder function in streptozotocin-diabetic rats were investigated. 2. Diabetes of 2 months duration resulted in decreases in body weight and increases in fluid consumption, urine volume, frequency of micturition, and average volume per micturition; effects which were prevented by insulin treatment. 3. Insulin treatment also prevented the increases in contractile responses of bladder body strips from diabetic rats to nerve stimulation, ATP, and bethanechol. 4. Diabetes of 4 months duration also resulted in decreases in body weight, and increases in fluid consumption, urine volume, frequency of micturition, and average volume per micturition, effects which were reversed by insulin treatment for the final 2 months of the study. 5. Insulin treatment reversed the increases in contractile responses of bladder body strips from diabetic rats to nerve stimulation, ATP, and bethanechol. 6. The data indicate that the effects of streptozotocin-induced diabetes on urinary bladder function are both prevented and reversed by insulin treatment.

streptozotocin

diabetes mellitus

streptozotocin

diabetic

Diabetes

diabetic

ATP

bethanechol

Diabetes

diabetic

ATP

bethanechol

streptozotocin

diabetes


Delayed institution of hypertension during focal cerebral ischemia: effect on brain edema.

The effect of induced hypertension instituted after a 2-h delay following middle cerebral artery occlusion (MCAO) on brain edema formation and histochemical injury was studied. Under isoflurane anesthesia, the MCA of 14 spontaneously hypertensive rats was occluded. In the control group (n = 7), the mean arterial pressure (MAP) was not manipulated. In the hypertensive group (n = 7), the MAP was elevated by 25-30 mm Hg beginning 2 h after MCAO. Four hours after MCAO, the rats were killed and the brains harvested. The brains were sectioned along coronal planes spanning the distribution of ischemia produced by MCAO. Specific gravity (SG) was determined in the subcortex and in two sites in the cortex (core and periphery of the ischemic territory). The extent of neuronal injury was determined by 2,3,5-triphenyltetrazolium staining. In the ischemic core, there was no difference in SG in the subcortex and cortex in the two groups. In the periphery of the ischemic territory, SG in the cortex was greater (less edema accumulation) in the hypertensive group (1.041 +/- 0.001 vs 1.039 +/- 0.001, P less than 0.05). The area of histochemical injury (as a percent of the cross-sectional area of the hemisphere) was less in the hypertensive group (33 +/- 3% vs 21 +/- 2%, P less than 0.05). The data indicate that phenylephrine-induced hypertension instituted 2 h after MCAO does not aggravate edema in the ischemic core, that it improves edema in the periphery of the ischemic territory, and that it reduces the area of histochemical neuronal dysfunction.

hypertension

cerebral ischemia

brain edema

hypertension

middle cerebral artery occlusion

MCAO

brain edema

isoflurane

hypertensive

hypertensive

MCAO

MCAO

ischemia

MCAO

ischemic

neuronal injury

ischemic

ischemic

edema

hypertensive

hypertensive

phenylephrine

hypertension

MCAO

edema

ischemic

edema

ischemic

neuronal dysfunction


Amiodarone pulmonary toxicity.

Amiodarone is an effective antiarrhythmic agent whose utility is limited by many side-effects, the most problematic being pneumonitis. The pulmonary toxicity of amiodarone is thought to result from direct injury related to the intracellular accumulation of phospholipid and T cell-mediated hypersensitivity pneumonitis. The clinical and radiographic features of amiodarone-induced pulmonary toxicity are characteristic but nonspecific. The diagnosis depends on exclusion of other entities, such as heart failure, infection, and malignancy. While withdrawal of amiodarone leads to clinical improvement in majority of cases, this is not always possible or advisable. Dose reduction or concomitant steroid therapy may have a role in selected patients.

Amiodarone

pulmonary toxicity

Amiodarone

pneumonitis

pulmonary toxicity

amiodarone

hypersensitivity pneumonitis

hypersensitivity

pneumonitis

amiodarone

pulmonary toxicity

heart failure

infection

malignancy

amiodarone

steroid


Light chain proteinuria and cellular mediated immunity in rifampin treated patients with tuberculosis.

Light chain proteinuria was found in 9 of 17 tuberculosis patients treated with rifampin. Concomitant assay of cellular mediated immunity in these patients using skin test antigen and a lymphokine in vitro test provided results that were different. Response to Varidase skin test antigen was negative for all eight tuberculosis patients tested, but there occurred a hyper-responsiveness of the lymphocytes of these eight patients to phytomitogen (PHA-P). as well as of those of seven other tuberculous patients. This last finding may be related to time of testing and/or endogenous serum binding of rifampin which could have inhibited mitogen activity for the lymphocyte.

proteinuria

rifampin

tuberculosis

proteinuria

tuberculosis

rifampin

tuberculosis

tuberculous

rifampin


Initial potassium loss and hypokalaemia during chlorthalidone administration in patients with essential hypertension: the influence of dietary sodium restriction.

To investigate the initial potassium loss and development of hypokalaemia during the administration of an oral diuretic, metabolic balance studies were performed in ten patients with essential hypertension who had shown hypokalaemia under prior oral diuretic treatment. Chlorthalidone (50 mg daily) was given for 14 days. Six patients received a normal-sodium diet and four a low-sodium (17 mmol/day) diet. All patients had a normal initial total body potassium (40K). The electrolyte balances, weight, bromide space, plasma renin activity, and aldosterone secretion rate were measured. In both groups a potassium deficit developed, with proportionally larger losses from the extracellular than from the intracellular compartment. In the normal-sodium group the highest mean potassium deficit was 176 mmol on day 9, after which some potassium was regained; in the low-sodium group the highest deficit was 276 mmol on day 13. The normal-sodium group showed an immediate but temporary rise of the renin and aldosterone levels; in the low-sodium group renin and aldosterone increased more slowly but remained elevated. It is concluded that dietary sodium restriction increases diuretic-induced potassium loss, presumably by an increased activity of the renin-angiotensin-aldosterone system, while sodium delivery to the distal renal tubules remains sufficiently high to allow increased potassium secretion.

potassium

hypokalaemia

chlorthalidone

hypertension

sodium

potassium

hypokalaemia

hypertension

hypokalaemia

Chlorthalidone

sodium

sodium

potassium

aldosterone

potassium

sodium

potassium

potassium

sodium

sodium

aldosterone

sodium

aldosterone

sodium

potassium

angiotensin

aldosterone

sodium

potassium


Dynamic response of blood vessel in acute renal failure.

In this study we postulated that during acute renal failure induced by gentamicin the transient or dynamic response of blood vessels could be affected, and that antioxidants can prevent the changes in dynamic responses of blood vessels. The new approach to ex vivo blood vessel experiments in which not only the end points of vessels response within the time interval is considered, but also dynamics of this response, was used in this paper. Our results confirm the alteration in dynamic response of blood vessels during the change of pressure in gentamicin-treated animals. The beneficial effects of vitamin C administration to gentamicin-treated animals are also confirmed through: lower level of blood urea and creatinine and higher level of potassium. The pressure dynamic responses of isolated blood vessels show a faster pressure change in gentamicin-treated animals (8.07 +/- 1.7 s vs. 5.64 +/- 0.18 s). Vitamin C administration induced slowdown of pressure change back to the control values. The pressure dynamic properties, quantitatively defined by comparative pressure dynamic and total pressure dynamic, confirm the alteration in dynamic response of blood vessels during the change of pressure in gentamicin-treated animals and beneficial effects of vitamin C administration.

acute renal failure

acute renal failure

gentamicin

gentamicin

vitamin C

gentamicin

urea

creatinine

potassium

gentamicin

Vitamin C

gentamicin

vitamin C


The hemodynamics of oxytocin and other vasoactive agents during neuraxial anesthesia for cesarean delivery: findings in six cases.

Oxytocin is a commonly used uterotonic that can cause significant and even fatal hypotension, particularly when given as a bolus. The resulting hypotension can be produced by a decrease in systemic vascular resistance or cardiac output through a decrease in venous return. Parturients with normal volume status, heart valves and pulmonary vasculature most often respond to this hypotension with a compensatory increase in heart rate and stroke volume. Oxytocin-induced hypotension at cesarean delivery may be incorrectly attributed to blood loss. Pulse power analysis (also called "pulse contour analysis") of an arterial pressure wave form allows continuous evaluation of systemic vascular resistance and cardiac output in real time, thereby elucidating the causative factors behind changes in blood pressure. Pulse power analysis was conducted in six cases of cesarean delivery performed under neuraxial anesthesia. Hypotension in response to oxytocin was associated with a decrease in systemic vascular resistance and a compensatory increase in stroke volume, heart rate and cardiac output. Pulse power analysis may be helpful in determining the etiology of and treating hypotension during cesarean delivery under neuraxial anesthesia.

oxytocin

Oxytocin

hypotension

hypotension

hypotension

stroke

Oxytocin

hypotension

blood loss

Hypotension

oxytocin

stroke

hypotension


Exaggerated expression of inflammatory mediators in vasoactive intestinal polypeptide knockout (VIP-/-) mice with cyclophosphamide (CYP)-induced cystitis.

Vasoactive intestinal polypeptide (VIP) is an immunomodulatory neuropeptide distributed in micturition pathways. VIP(-/-) mice exhibit altered bladder function and neurochemical properties in micturition pathways after cyclophosphamide (CYP)-induced cystitis. Given VIP's role as an anti-inflammatory mediator, we hypothesized that VIP(-/-) mice would exhibit enhanced inflammatory mediator expression after cystitis. A mouse inflammatory cytokine and receptor RT2 profiler array was used to determine regulated transcripts in the urinary bladder of wild type (WT) and VIP(-/-) mice with or without CYP-induced cystitis (150 mg/kg; i.p.; 48 h). Four binary comparisons were made: WT control versus CYP treatment (48 h), VIP(-/-) control versus CYP treatment (48 h), WT control versus VIP(-/-) control, and WT with CYP treatment (48 h) versus VIP(-/-) with CYP treatment (48 h). The genes presented represent (1) greater than 1.5-fold change in either direction and (2) the p value is less than 0.05 for the comparison being made. Several regulated genes were validated using enzyme-linked immunoassays including IL-1beta and CXCL1. CYP treatment significantly (p < or = 0.001) increased expression of CXCL1 and IL-1beta in the urinary bladder of WT and VIP(-/-) mice, but expression in VIP(-/-) mice with CYP treatment was significantly (p < or = 0.001) greater (4.2- to 13-fold increase) than that observed in WT urinary bladder (3.6- to 5-fold increase). The data suggest that in VIP(-/-) mice with bladder inflammation, inflammatory mediators are increased above that observed in WT with CYP. This shift in balance may contribute to increased bladder dysfunction in VIP(-/-) mice with bladder inflammation and altered neurochemical expression in micturition pathways.

cyclophosphamide

CYP

cystitis

cyclophosphamide

CYP

cystitis

cystitis

CYP

cystitis

CYP

CYP

CYP

CYP

CYP

CYP

bladder inflammation

CYP

bladder dysfunction

bladder inflammation


Intraocular pressure in patients with uveitis treated with fluocinolone acetonide implants.

OBJECTIVE: To report the incidence and management of elevated intraocular pressure (IOP) in patients with uveitis treated with the fluocinolone acetonide (FA) intravitreal implant. DESIGN: Pooled data from 3 multicenter, double-masked, randomized, controlled, phase 2b/3 clinical trials evaluating the safety and efficacy of the 0.59-mg or 2.1-mg FA intravitreal implant or standard therapy were analyzed. RESULTS: During the 3-year follow-up, 71.0% of implanted eyes had an IOP increase of 10 mm Hg or more than baseline and 55.1%, 24.7%, and 6.2% of eyes reached an IOP of 30 mm Hg or more, 40 mm Hg or more, and 50 mm Hg or more, respectively. Topical IOP-lowering medication was administered in 74.8% of implanted eyes, and IOP-lowering surgeries, most of which were trabeculectomies (76.2%), were performed on 36.6% of implanted eyes. Intraocular pressure-lowering surgeries were considered a success (postoperative IOP of 6-21 mm Hg with or without additional IOP-lowering medication) in 85.1% of eyes at 1 year. The rate of hypotony (IOP </= 5 mm Hg) following IOP-lowering surgery (42.5%) was not different from that of implanted eyes not subjected to surgery (35.4%) (P = .09). CONCLUSION: Elevated IOP is a significant complication with the FA intravitreal implant but may be controlled with medication and surgery.

uveitis

fluocinolone acetonide

elevated intraocular pressure

uveitis

fluocinolone acetonide

FA

FA

hypotony


Pallidal stimulation: an alternative to pallidotomy?

A resurgence of interest in the surgical treatment of Parkinson's disease (PD) came with the rediscovery of posteroventral pallidotomy by Laitinen in 1985. Laitinen's procedure improved most symptoms in drug-resistant PD, which engendered wide interest in the neurosurgical community. Another lesioning procedure, ventrolateral thalamotomy, has become a powerful alternative to stimulate the nucleus ventralis intermedius, producing high long-term success rates and low morbidity rates. Pallidal stimulation has not met with the same success. According to the literature pallidotomy improves the "on" symptoms of PD, such as dyskinesias, as well as the "off" symptoms, such as rigidity, bradykinesia, and on-off fluctuations. Pallidal stimulation improves bradykinesia and rigidity to a minor extent; however, its strength seems to be in improving levodopa-induced dyskinesias. Stimulation often produces an improvement in the hyper- or dyskinetic upper limbs, but increases the "freezing" phenomenon in the lower limbs at the same time. Considering the small increase in the patient's independence, the high costs of bilateral implants, and the difficulty most patients experience in handling the devices, the question arises as to whether bilateral pallidal stimulation is a real alternative to pallidotomy.

Parkinson's disease

PD

PD

PD

dyskinesias

rigidity

bradykinesia

bradykinesia

rigidity

levodopa

dyskinesias

hyper- or dyskinetic


Case report: Dexatrim (Phenylpropanolamine) as a cause of myocardial infarction.

Phenylpropanolamine (PPA) is a sympathetic amine used in over-the-counter cold remedies and weight-control preparations worldwide. Its use has been associated with hypertensive episodes and hemorrhagic strokes in younger women. Several reports have linked the abuse of PPA with myocardial injury, especially when overdose is involved. We report here the first case of Dexatrim (PPA)-induced myocardial injury in a young woman who was using it at recommended doses for weight control. In addition, we review the 7 other cases of PPA related myocardial injury that have been reported so far. Physicians and patients should be alert to the potential cardiac risk associated with the use of PPA, even at doses generally considered to be safe.

Dexatrim

Phenylpropanolamine

myocardial infarction

Phenylpropanolamine

PPA

amine

hypertensive

hemorrhagic strokes

hemorrhagic

strokes

PPA

myocardial injury

overdose

Dexatrim

PPA

myocardial injury

PPA

myocardial injury

PPA


Risperidone-associated, benign transient visual disturbances in schizophrenic patients with a past history of LSD abuse.

Two schizophrenic patients, who had a prior history of LSD abuse and who had previously developed EPS with classic antipsychotics, were successfully treated with risperidone. They both reported short episodes of transient visual disturbances, which appeared immediately after starting treatment with risperidone. This imagery resembled visual disturbances previously experienced as "flashbacks" related to prior LSD consumption. Risperidone administration was continued and the visual disturbances gradually wore off. During a six-month follow-up period, there was no recurrence of visual disturbances. This phenomenon may be interpreted as a benign, short-term and self-limiting side effect which does not contraindicate the use of risperidone or interfere with treatment. Conclusions based on two case reports should be taken with appropriate caution.

Risperidone

visual disturbances

schizophrenic

LSD

schizophrenic

LSD

EPS

risperidone

visual disturbances

risperidone

visual disturbances

LSD

Risperidone

visual disturbances

visual disturbances

risperidone


Activation of poly(ADP-ribose) polymerase contributes to development of doxorubicin-induced heart failure.

Activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) by oxidant-mediated DNA damage is an important pathway of cell dysfunction and tissue injury in conditions associated with oxidative stress. Increased oxidative stress is a major factor implicated in the cardiotoxicity of doxorubicin (DOX), a widely used antitumor anthracycline antibiotic. Thus, we hypothesized that the activation of PARP may contribute to the DOX-induced cardiotoxicity. Using a dual approach of PARP-1 suppression, by genetic deletion or pharmacological inhibition with the phenanthridinone PARP inhibitor PJ34, we now demonstrate the role of PARP in the development of cardiac dysfunction induced by DOX. PARP-1+/+ and PARP-1-/- mice received a single injection of DOX (25 mg/kg i.p). Five days after DOX administration, left ventricular performance was significantly depressed in PARP-1+/+ mice, but only to a smaller extent in PARP-1-/- ones. Similar experiments were conducted in BALB/c mice treated with PJ34 or vehicle. Treatment with a PJ34 significantly improved cardiac dysfunction and increased the survival of the animals. In addition PJ34 significantly reduced the DOX-induced increase in the serum lactate dehydrogenase and creatine kinase activities but not metalloproteinase activation in the heart. Thus, PARP activation contributes to the cardiotoxicity of DOX. PARP inhibitors may exert protective effects against the development of severe cardiac complications associated with the DOX treatment.

poly(ADP-ribose)

doxorubicin

heart failure

poly(ADP-ribose)

cardiotoxicity

doxorubicin

DOX

anthracycline

DOX

cardiotoxicity

cardiac dysfunction

DOX

DOX

DOX

cardiac dysfunction

DOX

lactate

creatine

cardiotoxicity

DOX

cardiac complications

DOX


Fluconazole-induced torsade de pointes.

OBJECTIVE: To present a case of fluconazole-associated torsade de pointes (TDP) and discuss fluconazole's role in causing TDP. CASE SUMMARY: A 68-year-old white woman with Candida glabrata isolated from a presacral abscess developed TDP eight days after commencing oral fluconazole The patient had no other risk factors for TDP, including coronary artery disease, cardiomyopathy, congestive heart failure, and electrolyte abnormalities There was a temporal association between the initiation of fluconazole and TDP. The TDP resolved when fluconazole was discontinued; however, the patient continued to have premature ventricular contractions and nonsustained ventricular tachycardia (NSVT) until six days after drug cessation DISCUSSION: Use of the Naranjo probability scale indicates a probable relationship between the use of fluconazole and the development of TDP. The possible mechanism is depression of rapidly activating delayed rectifier potassium currents. In our patient, there was no other etiology identified that could explain QT prolongation or TDP The complete disappearance of NSVT and premature ventricular contractions followed by normalization of QT interval after the drug was stopped strongly suggests fluconazole as the etiology. CONCLUSIONS: Clinicians should be aware that fluconazole, even at low doses, may cause prolongation of the QT interval, leading to TDP. Serial electrocardiographic monitoring may be considered when fluconazole is administered in patients who are at risk for ventricular arrhythmias.

Fluconazole

torsade de pointes

fluconazole

torsade de pointes

TDP

fluconazole

TDP

TDP

fluconazole

TDP

coronary artery disease

cardiomyopathy

congestive heart failure

fluconazole

TDP

TDP

fluconazole

premature ventricular contractions

ventricular tachycardia

NSVT

fluconazole

TDP

depression

potassium

QT prolongation

TDP

NSVT

premature ventricular contractions

fluconazole

fluconazole

prolongation of the QT interval

TDP

fluconazole

ventricular arrhythmias


High-dose methylprednisolone may do more harm for spinal cord injury.

Because of the National Acute Spinal Cord Injury Studies (NASCIS), high-dose methylprednisolone became the standard of care for the acute spinal cord injury. In the NASCIS, there was no mention regarding the possibility of acute corticosteroid myopathy that high-dose methylprednisolone may cause. The dosage of methylprednisolone recommended by the NASCIS 3 is the highest dose of steroids ever being used during a 2-day period for any clinical condition. We hypothesize that it may cause some damage to the muscle of spinal cord injury patients. Further, steroid myopathy recovers naturally and the neurological improvement shown in the NASCIS may be just a recording of this natural motor recovery from the steroid myopathy, instead of any protection that methylprednisolone offers to the spinal cord injury. To our knowledge, this is the first discussion considering the possibility that the methylprednisolone recommended by NASCIS may cause acute corticosteroid myopathy.

methylprednisolone

spinal cord injury

Spinal Cord Injury

methylprednisolone

spinal cord injury

corticosteroid

myopathy

methylprednisolone

methylprednisolone

steroids

damage to the muscle

spinal cord injury

steroid

myopathy

steroid

myopathy

methylprednisolone

spinal cord injury

methylprednisolone

corticosteroid

myopathy


Probing peripheral and central cholinergic system responses.

OBJECTIVE: The pharmacological response to drugs that act on the cholinergic system of the iris has been used to predict deficits in central cholinergic functioning due to diseases such as Alzheimer's disease, yet correlations between central and peripheral responses have not been properly studied. This study assessed the effect of normal aging on (1) the tropicamide-induced increase in pupil diameter, and (2) the reversal of this effect with pilocarpine. Scopolamine was used as a positive control to detect age-dependent changes in central cholinergic functioning in the elderly. DESIGN: Randomized double-blind controlled trial. PARTICIPANTS: Ten healthy elderly (mean age 70) and 9 young (mean age 33) volunteers. INTERVENTIONS: Pupil diameter was monitored using a computerized infrared pupillometer over 4 hours. The study involved 4 sessions. In 1 session, tropicamide (20 microL, 0.01%) was administered to one eye and placebo to the other. In another session, tropicamide (20 microL, 0.01%) was administered to both eyes, followed 23 minutes later by the application of pilocarpine (20 microL, 0.1%) to one eye and placebo to the other. All eye drops were given in a randomized order. In 2 separate sessions, a single dose of scopolamine (0.5 mg, intravenously) or placebo was administered, and the effects on word recall were measured using the Buschke Selective Reminding Test over 2 hours. OUTCOME MEASURES: Pupil size at time points after administration of tropicamide and pilocarpine; scopolamine-induced impairment in word recall. RESULTS: There was no significant difference between elderly and young volunteers in pupillary response to tropicamide at any time point (p > 0.05). The elderly group had a significantly greater pilocarpine-induced net decrease in pupil size 85, 125, 165 and 215 minutes after administration, compared with the young group (p < 0.05). Compared with the young group, the elderly group had greater scopolamine-induced impairment in word recall 60, 90 and 120 minutes after administration (p < 0.05). CONCLUSION: There is an age-related pupillary response to pilocarpine that is not found with tropicamide. Thus, pilocarpine may be useful to assess variations in central cholinergic function in elderly patients.

Alzheimer's disease

tropicamide

pilocarpine

Scopolamine

tropicamide

tropicamide

pilocarpine

scopolamine

tropicamide

pilocarpine

scopolamine

impairment in word recall

tropicamide

pilocarpine

scopolamine

impairment in word recall

pilocarpine

tropicamide

pilocarpine


Acetazolamide-induced Gerstmann syndrome.

Acute confusion induced by acetazolamide is a well known adverse drug reaction in patients with renal impairment. We report a case of acetazolamide-induced Gerstmann syndrome in a patient with normal renal function, to highlight predisposing factors that are frequently overlooked.

Acetazolamide

Gerstmann syndrome

confusion

acetazolamide

renal impairment

acetazolamide

Gerstmann syndrome


Hypomania-like syndrome induced by olanzapine.

We report a female patient with a diagnosis of a not otherwise specified psychotic disorder (DSM-IV) who developed hypomania shortly after the introduction of olanzapine treatment.

Hypomania

olanzapine

psychotic disorder

hypomania

olanzapine


Neutrophil superoxide and hydrogen peroxide production in patients with acute liver failure.

Defects in superoxide and hydrogen peroxide production may be implicated in the high incidence of bacterial infections in patients with acute liver failure (ALF). In the present study, oxygen radical production in patients with ALF due to paracetamol overdose was compared with that of healthy volunteers. Neutrophils from 14 ALF patients were stimulated via the complement receptors using zymosan opsonized with ALF or control serum. Superoxide and hydrogen peroxide production by ALF neutrophils stimulated with zymosan opsonized with ALF serum was significantly reduced compared with the control subjects (P < 0.01). This defect persisted when zymosan opsonized by control serum was used (P < 0.05). Superoxide and hydrogen peroxide production in neutrophils stimulated with formyl-methionyl-leucyl-phenylalanine (fMLP) from a further 18 ALF patients was unaffected compared with control neutrophils. Serum C3 complement levels were significantly reduced in ALF patients compared with control subjects (P < 0.0005). These results demonstrate a neutrophil defect in ALF due to paracetamol overdose, that is complement dependent but independent of serum complement, possibly connected to the complement receptor.

superoxide

hydrogen peroxide

acute liver failure

superoxide

hydrogen peroxide

bacterial infections

acute liver failure

ALF

oxygen

ALF

paracetamol

overdose

ALF

ALF

Superoxide

hydrogen peroxide

ALF

ALF

Superoxide

hydrogen peroxide

formyl-methionyl-leucyl-phenylalanine

fMLP

ALF

ALF

ALF

paracetamol

overdose


Absence of effect of sertraline on time-based sensitization of cognitive impairment with haloperidol.

This double-blind, randomized, placebo-controlled study evaluated the effects of haloperidol alone and haloperidol plus sertraline on cognitive and psychomotor function in 24 healthy male subjects. METHOD: All subjects received placebo on Day 1 and haloperidol 2 mg on Days 2 and 25. From Days 9 to 25, subjects were randomly assigned to either sertraline (12 subjects) or placebo (12 subjects); the sertraline dose was titrated from 50 to 200 mg/day from Days 9 to 16, and remained at 200 mg/day for the final 10 days of the drug administration period. Cognitive function testing was performed before dosing and over a 24-hour period after dosing on Days 1, 2, and 25. RESULTS: Impairment of cognitive function was observed 6 to 8 hours after administration of haloperidol on Day 2 but was not evident 23 hours after dosing. When single-dose haloperidol was given again 25 days later, greater impairment with earlier onset was noted in several tests in both treatment groups, suggesting enhancement of this effect. There was no indication that sertraline exacerbated the impairment produced by haloperidol since an equivalent effect also occurred in the placebo group. Three subjects (2 on sertraline and 1 on placebo) withdrew from the study because of side effects. Ten subjects in each group reported side effects related to treatment. The side effect profiles of sertraline and of placebo were similar. CONCLUSION: Haloperidol produced a clear profile of cognitive impairment that was not worsened by concomitant sertraline administration.

sertraline

cognitive impairment

haloperidol

haloperidol

haloperidol

sertraline

haloperidol

sertraline

sertraline

Impairment of cognitive function

haloperidol

haloperidol

sertraline

haloperidol

sertraline

sertraline

Haloperidol

cognitive impairment

sertraline


Ciprofloxacin-induced nephrotoxicity in patients with cancer.

Nephrotoxicity associated with ciprofloxacin is uncommon. Five patients with cancer who developed acute renal failure that followed treatment with ciprofloxacin are described and an additional 15 cases reported in the literature are reviewed. Other than elevation of serum creatinine levels, characteristic clinical manifestations and abnormal laboratory findings are not frequently present. Allergic interstitial nephritis is believed to be the underlying pathological-process. Definitive diagnosis requires performance of renal biopsy, although this is not always feasible. An improvement in renal function that followed the discontinuation of the offending antibiotic supports the presumptive diagnosis of ciprofloxacin-induced acute renal failure.

Ciprofloxacin

nephrotoxicity

cancer

Nephrotoxicity

ciprofloxacin

cancer

acute renal failure

ciprofloxacin

creatinine

interstitial nephritis

ciprofloxacin

acute renal failure


Case report: pentamidine and polymorphic ventricular tachycardia revisited.

Pentamidine isethionate has been associated with ventricular tachyarrhythmias, including torsade de pointes. This article reports two cases of this complication and reviews all reported cases to date. Pentamidine-induced torsade de pointes may be related to serum magnesium levels and hypomagnesemia may synergistically induce torsade. Torsade de pointes occurred after an average of 10 days of treatment with pentamidine. In these patients, no other acute side effects of pentamidine were observed. Torsade de pointes can be treated when recognized early, possibly without discontinuation of pentamidine. When QTc interval prolongation is observed, early magnesium supplementation is advocated.

pentamidine

ventricular tachycardia

Pentamidine isethionate

ventricular tachyarrhythmias

torsade de pointes

Pentamidine

torsade de pointes

magnesium

hypomagnesemia

Torsade de pointes

pentamidine

pentamidine

Torsade de pointes

pentamidine

QTc interval prolongation

magnesium


Time dependence of plasma malondialdehyde, oxypurines, and nucleosides during incomplete cerebral ischemia in the rat.

Incomplete cerebral ischemia (30 min) was induced in the rat by bilaterally clamping the common carotid arteries. Peripheral venous blood samples were withdrawn from the femoral vein four times (once every 5 min) before ischemia (0 time) and 5, 15, and 30 min after ischemia. Plasma extracts were analyzed by a highly sensitive high-performance liquid chromatographic method for the direct determination of malondialdehyde, oxypurines, and nucleosides. During ischemia, a time-dependent increase of plasma oxypurines and nucleosides was observed. Plasma malondialdehyde, which was present in minimal amount at zero time (0.058 mumol/liter plasma; SD 0.015), increased after 5 min of ischemia, resulting in a fivefold increase after 30 min of carotid occlusion (0.298 mumol/liter plasma; SD 0.078). Increased plasma malondialdehyde was also recorded in two other groups of animals subjected to the same experimental model, one receiving 20 mg/kg b.w. of the cyclooxygenase inhibitor acetylsalicylate intravenously immediately before ischemia, the other receiving 650 micrograms/kg b.w. of the hypotensive drug nitroprusside at a flow rate of 103 microliters/min intravenously during ischemia, although in this latter group malondialdehyde was significantly higher. The present data indicate that the determination of malondialdehyde, oxypurines, and nucleosides in peripheral blood, may be used to monitor the metabolic alterations of tissues occurring during ischemic phenomena.(ABSTRACT TRUNCATED AT 250 WORDS)

malondialdehyde

oxypurines

nucleosides

cerebral ischemia

cerebral ischemia

ischemia

ischemia

malondialdehyde

oxypurines

nucleosides

ischemia

oxypurines

nucleosides

malondialdehyde

ischemia

malondialdehyde

acetylsalicylate

ischemia

hypotensive

nitroprusside

ischemia

malondialdehyde

malondialdehyde

oxypurines

nucleosides

ischemic


Cholinergic toxicity resulting from ocular instillation of echothiophate iodide eye drops.

A patient developed a severe cholinergic syndrome from the use of echothiophate iodide ophthalmic drops, presented with profound muscle weakness and was initially given the diagnosis of myasthenia gravis. Red blood cell and serum cholinesterase levels were severely depressed and symptoms resolved spontaneously following discontinuation of the eye drops.

toxicity

echothiophate iodide

echothiophate iodide

muscle weakness

myasthenia gravis


Acute renal failure in high dose carboplatin chemotherapy.

Carboplatin has been reported to cause acute renal failure when administered in high doses to adult patients. We report a 4 1/2-year-old girl who was treated with high-dose carboplatin for metastatic parameningeal embryonal rhabdomyosarcoma. Acute renal failure developed followed by a slow partial recovery of renal function. Possible contributing factors are discussed.

Acute renal failure

carboplatin

Carboplatin

acute renal failure

carboplatin

embryonal rhabdomyosarcoma

Acute renal failure


Endometrial carcinoma after Hodgkin disease in childhood.

A 34-year-old patient developed metastic endometrial carcinoma after Hodgkin disease in childhood. She had ovarian failure after abdominal irradiation and chemotherapy for Hodgkin disease, and received exogenous estrogens, a treatment implicated in the development of endometrial cancer in menopausal women. Young women on replacement estrogens for ovarian failure after cancer therapy may also have increased risk of endometrial carcinoma and should be examined periodically.

Endometrial carcinoma

Hodgkin disease

endometrial carcinoma

Hodgkin disease

ovarian failure

Hodgkin disease

estrogens

endometrial cancer

estrogens

ovarian failure

cancer

endometrial carcinoma


Induction of the obstructive sleep apnea syndrome in a woman by exogenous androgen administration.

We documented airway occlusion during sleep and an abnormally high supraglottic resistance while awake in a 54-yr-old woman who had developed physical changes and the syndrome of obstructive sleep apnea while being administered exogenous androgens. When the androgens were withdrawn, the patient's physical changes, symptoms, sleep study, and supraglottic resistance all returned to normal. A rechallenge with androgen produced symptoms of obstructive sleep apnea that abated upon withdrawal of the hormone. Previous reports have favored a role of androgens in the pathogenesis of sleep apnea. Our report provides direct evidence for this role. Structural and functional measurements indicate that androgens exert a permissive or necessary action on the structural configuration of the oropharynx that predisposes to obstruction during sleep. Development of the obstructive sleep apnea syndrome must be considered a possible side effect of androgen therapy.

obstructive sleep apnea syndrome

androgen

syndrome of obstructive sleep apnea

androgens

androgens

androgen

obstructive sleep apnea

androgens

sleep apnea

androgens

obstructive sleep apnea syndrome

androgen


Effect of captopril on pre-existing and aminonucleoside-induced proteinuria in spontaneously hypertensive rats.

Proteinuria is a side effect of captopril treatment in hypertensive patients. The possibility of reproducing the same renal abnormality with captopril was examined in SHR. Oral administration of captopril at 100 mg/kg for 14 days failed to aggravate proteinuria pre-existing in SHR. Also, captopril treatment failed to potentiate or facilitate development of massive proteinuria invoked by puromycin aminonucleoside in SHR. Captopril had little or no demonstrable effects on serum electrolyte concentrations, excretion of urine, sodium and potassium, endogenous creatinine clearance, body weight, and food and water consumption. However, ketone bodies were consistently present in urine and several lethalities occurred during multiple dosing of captopril in SHR.

captopril

aminonucleoside

proteinuria

hypertensive

Proteinuria

captopril

hypertensive

renal abnormality

captopril

captopril

proteinuria

captopril

proteinuria

puromycin aminonucleoside

Captopril

sodium

potassium

creatinine

ketone

captopril


Epileptogenic properties of enflurane and their clinical interpretation.

Three cases of EEG changes induced by single exposure to enflurane anesthesia are reported. In one patient, enflurane administered during a donor nephrectomy resulted in unexpected partial motor seizures. Until the cause of the seizures was correctly identified, the patient was inappropriately treated with anticonvulsants. Two other patients suffered from partial, complex and generalized seizures uncontrolled by medication. Epileptic foci delineated and activated by enflurane were surgically ablated and the patients are now seizure-free. Previous exposures to enflurane have to be disclosed to avoid mistakes in clinical interpretation of the EEG. On the other hand, enflurane may prove to be a safe fast acting activator of epileptic foci during corticography or depth electrode intraoperative recordings.

enflurane

enflurane

enflurane

seizures

seizures

seizures

Epileptic

enflurane

seizure

enflurane

enflurane

epileptic


Reversible cerebral lesions associated with tiazofurin usage: MR demonstration.

Tiazofurin is an experimental chemotherapeutic agent currently undergoing clinical evaluation. We report our results with magnetic resonance (MR) in demonstrating reversible cerebral abnormalities concurrent with the use of this drug. The abnormalities on MR were correlated with findings on CT as well as with cerebral angiography. The utility of MR in the evaluation of patients receiving this new agent is illustrated.

cerebral lesions

tiazofurin

Tiazofurin

cerebral abnormalities


Antagonism of diazepam-induced sedative effects by Ro15-1788 in patients after surgery under lumbar epidural block. A double-blind placebo-controlled investigation of efficacy and safety.

The aim of this study was to assess the efficacy of Ro15-1788 and a placebo in reversing diazepam-induced effects after surgery under epidural block, and to evaluate the local tolerance and general safety of Ro15-1788. Fifty-seven patients were sedated with diazepam for surgery under epidural anaesthesia. Antagonism of diazepam-induced effects by Ro15-1788 was investigated postoperatively in a double-blind placebo-controlled trial. The patient's subjective assessment of mood rating, an objective test of performance, a test for amnesia, and vital signs were recorded for up to 300 min after administration of the trial drug. No significant differences between the two groups were observed for mood rating, amnesia, or vital signs. The Ro15-1788 group showed a significant improvement in the performance test up to 120 min after administration of the drug. There was no evidence of reaction at the injection site.

diazepam

diazepam

diazepam

diazepam

amnesia

amnesia


Enhanced stimulus-induced neurotransmitter overflow in epinephrine-induced hypertensive rats is not mediated by prejunctional beta-adrenoceptor activation.

The present study examines the effect of 6-day epinephrine treatment (100 micrograms/kg per h, s.c.) on stimulus-induced (1 Hz) endogenous neurotransmitter overflow from the isolated perfused kidney of vehicle- and epinephrine-treated rats. Renal catecholamine stores and stimulus-induced overflow in the vehicle-treated group consisted of norepinephrine only. However, epinephrine treatment resulted in the incorporation of epinephrine into renal catecholamine stores such that approximately 40% of the catecholamine present was epinephrine while the norepinephrine content was reduced by a similar degree. Total tissue catecholamine content of the kidney on a molar basis was unchanged. Stimulus-induced fractional overflow of neurotransmitter from the epinephrine-treated kidneys was approximately twice normal and consisted of both norepinephrine and epinephrine in proportions similar to those found in the kidney. This difference in fractional overflow between groups was not affected by neuronal and extraneuronal uptake blockade. Propranolol had no effect on stimulus-induced overflow in either group. Phentolamine increased stimulus-induced overflow in both groups although the increment in overflow was greater in the epinephrine-treated group. In conclusion, chronic epinephrine treatment results in enhanced fractional neurotransmitter overflow. However, neither alterations in prejunctional beta-adrenoceptor influences nor alterations in neuronal and extraneuronal uptake mechanisms appear to be responsible for this alteration. Furthermore, data obtained with phentolamine alone do not suggest alpha-adrenoceptor desensitization as the cause of the enhanced neurotransmitter overflow after epinephrine treatment.

epinephrine

hypertensive

epinephrine

epinephrine

catecholamine

norepinephrine

epinephrine

epinephrine

catecholamine

catecholamine

epinephrine

norepinephrine

catecholamine

epinephrine

norepinephrine

epinephrine

Propranolol

Phentolamine

epinephrine

epinephrine

phentolamine

epinephrine


Ocular manifestations of juvenile rheumatoid arthritis.

We followed 210 cases of juvenile rheumatoid arthritis closely for eleven years. Thirty-six of the 210 patients (17.2%) developed iridocyclitis. Iridocyclitis was seen most frequently in young female patients (0 to 4 years) with the monoarticular or pauciatricular form of the arthritis. However, 30% of the patients developed uveitis after 16 years of age. Although 61% of patients had a noncontributory ocular history on entry, 42% had active uveitis on entry. Our approach was effective in detecting uveitis in new cases and exacerbations of uveitis in established cases. Forty-four percent of patients with uveitis had one or more identifiable signs or symptoms, such as red eye, ocular pain, decreased visual acuity, or photophobia, in order of decreasing frequency. Even after early detection and prompt treatment, 41% of cases of uveitis did not respond to more than six months of intensive topical treatment with corticosteroids and mydriatics. Despite this, there was a dramatic decrease in the 50% incidence of blinding complications of uveitis cited in earlier studies. Cataract and band keratopathy occurred in only 22 and 13% of our group, respectively. We used chloroquine or hydroxychloroquine in 173 of 210 cases and found only one case of chorioretinopathy attributable to these drugs. Systemically administered corticosteroids were used in 75 of 210 cases; a significant number of posterior subcapsular cataracts was found. Typical keratoconjunctivitis sicca developed in three of the uveitis cases. This association with uveitis and JRA was not noted previously. Surgical treatment of cataracts, band keratopathy, and glaucoma achieved uniformly discouraging results.

juvenile rheumatoid arthritis

juvenile rheumatoid arthritis

iridocyclitis

Iridocyclitis

arthritis

uveitis

uveitis

uveitis

uveitis

uveitis

ocular pain

decreased visual acuity

photophobia

uveitis

corticosteroids

uveitis

Cataract

band keratopathy

chloroquine

hydroxychloroquine

chorioretinopathy

corticosteroids

cataracts

keratoconjunctivitis

uveitis

uveitis

cataracts

band keratopathy

glaucoma


Water intoxication associated with oxytocin administration during saline-induced abortion.

Four cases of water intoxication in connection with oxytocin administration during saline-induced abortions are described. The mechanism of water intoxication is discussed in regard to these cases. Oxytocin administration during midtrimester-induced abortions is advocated only if it can be carried out under careful observations of an alert nursing staff, aware of the symptoms of water intoxication and instructed to watch the diuresis and report such early signs of the syndrome as asthenia, muscular irritability, or headaches. The oxytocin should be given only in Ringers lactate or, alternately, in Ringers lactate and a 5 per cent dextrose and water solutions. The urinary output should be monitored and the oxytocin administration discontinued and the serum electrolytes checked if the urinary output decreases. The oxytocin should not be administered in excess of 36 hours. If the patient has not aborted by then the oxytocin should be discontinued for 10 to 12 hours in order to perform electrolyte determinations and correct any electrolyte imbalance.

Water intoxication

oxytocin

abortion

water intoxication

oxytocin

abortions

water intoxication

Oxytocin

abortions

water intoxication

asthenia

irritability

headaches

oxytocin

lactate

lactate

dextrose

oxytocin

oxytocin

oxytocin