Input: Chronic carbamazepine inhibits the development of local anesthetic seizures kindled by cocaine and lidocaine. The effects of carbamazepine (CBZ) treatment on local anesthetic - kindled seizures and lethality were evaluated in different stages of the kindling process and under different methods of CBZ administration. Chronic oral CBZ inhibited the development of both lidocaine - and cocaine - induced seizures, but had little effect on the fully developed local anesthetic seizures. Chronic CBZ also decreased the incidence of seizure - related mortality in the cocaine - injected rats. Acute CBZ over a range of doses (15 - 50 mg / kg) had no effect on completed lidocaine - kindled or acute cocaine - induced seizures. Repeated i. p. injection of CBZ (15 mg / kg) also was without effect on the development of lidocaine - or cocaine - kindled seizures. The differential effects of CBZ depending upon stage of seizure development suggest that distinct mechanisms underlie the development versus maintenance of local anesthetic - kindled seizures. The effectiveness of chronic but not repeated, intermittent injections of CBZ suggests that different biochemical consequences result from the different treatment regimens. The possible utility of chronic CBZ in preventing the development of toxic side effects in human cocaine users is suggested by these data, but remains to be directly evaluated.

carbamazepine

cocaine

lidocaine

carbamazepine

CBZ

CBZ

CBZ

lidocaine

cocaine

CBZ

cocaine

CBZ

lidocaine

cocaine

CBZ

lidocaine

cocaine

CBZ

CBZ

CBZ

cocaine

seizures

seizures

seizures

seizures

seizure

seizures

seizures

seizure

seizures

lidocaine

seizures

lidocaine

seizures

lidocaine

seizures

lidocaine

seizures

lidocaine

seizure

lidocaine

seizures

lidocaine

seizures

lidocaine

seizure

lidocaine

seizures

lidocaine

seizures

lidocaine

seizures

lidocaine

seizures

lidocaine

seizures

lidocaine

seizure

lidocaine

seizures

lidocaine

seizures

lidocaine

seizure

lidocaine

seizures

lidocaine

seizures

lidocaine

seizures

lidocaine

seizures

lidocaine

seizures

lidocaine

seizure

lidocaine

seizures

lidocaine

seizures

lidocaine

seizure

lidocaine

seizures

lidocaine

seizures

lidocaine

seizures

lidocaine

seizures

lidocaine

seizures

lidocaine

seizure

lidocaine

seizures

lidocaine

seizures

lidocaine

seizure

lidocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizure

cocaine

seizures

cocaine

seizures

cocaine

seizure

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizure

cocaine

seizures

cocaine

seizures

cocaine

seizure

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizure

cocaine

seizures

cocaine

seizures

cocaine

seizure

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizure

cocaine

seizures

cocaine

seizures

cocaine

seizure

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizure

cocaine

seizures

cocaine

seizures

cocaine

seizure

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizure

cocaine

seizures

cocaine

seizures

cocaine

seizure

cocaine

seizures


Input: D - penicillamine in the treatment of localized scleroderma. Localized scleroderma has no recognized internal organ involvement but may be disfiguring and disabling when the cutaneous lesions are extensive or affect children. There is no accepted or proven treatment for localized scleroderma. Case reports of 11 patients with severe, extensive localized scleroderma who were treated with D - penicillamine are summarized in this article. This drug was judged to have a favorable effect on the disease course in 7 (64%) of 11 patients. Improvement began within 3 to 6 months and consisted of cessation of active cutaneous lesions in all 7 patients, skin softening in 5, and more normal growth of the affected limb in 2 of 3 children. Joint stiffness and contractures also improved. The dose of D - penicillamine associated with a favorable response was as low as 2 to 5 mg / kg per day given over a period ranging from 15 to 53 months. D - Penicillamine caused nephrotic syndrome in 1 patient and milder reversible proteinuria in 3 other patients; none developed renal insufficiency. These data suggest that D - penicillamine may be effective in severe cases of localized scleroderma.

D - penicillamine

D - penicillamine

D - penicillamine

D - Penicillamine

D - penicillamine

localized scleroderma

Localized scleroderma

localized scleroderma

localized scleroderma

contractures

nephrotic syndrome

proteinuria

renal insufficiency

localized scleroderma

D - penicillamine

nephrotic syndrome

D - penicillamine

nephrotic syndrome

D - penicillamine

nephrotic syndrome

D - Penicillamine

nephrotic syndrome

D - penicillamine

nephrotic syndrome

D - penicillamine

proteinuria

D - penicillamine

proteinuria

D - penicillamine

proteinuria

D - Penicillamine

proteinuria

D - penicillamine

proteinuria


Input: Preservation of renal blood flow during hypotension induced with fenoldopam in dogs. The introduction of drugs that could induce hypotension with different pharmacological actions would be advantageous because side effects unique to a specific drug could be minimized by selecting appropriate therapy. Specific dopamine - 1, (DA1) and dopamine - 2 (DA2) receptor agonists are now under clinical investigation. Fenoldopam mesylate is a specific DA1 receptor agonist that lowers blood pressure by vasodilatation. The hypothesis that fenoldopam could be used to induce hypotension and preserve blood flow to the kidney was tested. Systemic aortic blood pressure and renal blood flow were measured continuously with a carotid arterial catheter and an electromagnetic flow probe respectively, in order to compare the cardiovascular and renal vascular effects of fenoldopam and sodium nitroprusside in ten dogs under halothane general anaesthesia. Mean arterial pressure was decreased 30 + / - 8 per cent from control with infusion of fenoldopam (3. 4 + / - 2. 0 micrograms. kg - 1. min - 1) and 34 + / - 4 per cent with infusion of sodium nitroprusside (5. 9 micrograms. kg - 1. min - 1) (NS). Renal blood flow (RBF) increased during fenoldopam - induced hypotension 11 + / - 7 per cent and decreased 21 + / - 8 per cent during sodium nitroprusside - induced hypotension (P less than 0. 01). Sodium nitroprusside is a non - selective arteriolar and venous vasodilator that can produce redistribution of blood flow away from the kidney during induced hypotension. Fenoldopam is a selective dopamine - 1 (DA1) receptor agonist that causes vasodilatation to the kidney and other organs with DA1 receptors and preserves blood flow to the kidney during induced hypotension.

hypotension

hypotension

hypotension

hypotension

hypotension

hypotension

hypotension

fenoldopam

dopamine

dopamine

Fenoldopam mesylate

fenoldopam

fenoldopam

sodium

nitroprusside

halothane

fenoldopam

sodium

nitroprusside

fenoldopam

sodium

nitroprusside

nitroprusside

dopamine

fenoldopam

hypotension

fenoldopam

hypotension

fenoldopam

hypotension

fenoldopam

hypotension

fenoldopam

hypotension

fenoldopam

hypotension

fenoldopam

hypotension

Fenoldopam mesylate

hypotension

Fenoldopam mesylate

hypotension

Fenoldopam mesylate

hypotension

Fenoldopam mesylate

hypotension

Fenoldopam mesylate

hypotension

Fenoldopam mesylate

hypotension

Fenoldopam mesylate

hypotension

fenoldopam

hypotension

fenoldopam

hypotension

fenoldopam

hypotension

fenoldopam

hypotension

fenoldopam

hypotension

fenoldopam

hypotension

fenoldopam

hypotension

fenoldopam

hypotension

fenoldopam

hypotension

fenoldopam

hypotension

fenoldopam

hypotension

fenoldopam

hypotension

fenoldopam

hypotension

fenoldopam

hypotension

fenoldopam

hypotension

fenoldopam

hypotension

fenoldopam

hypotension

fenoldopam

hypotension

fenoldopam

hypotension

fenoldopam

hypotension

fenoldopam

hypotension

fenoldopam

hypotension

fenoldopam

hypotension

fenoldopam

hypotension

fenoldopam

hypotension

fenoldopam

hypotension

fenoldopam

hypotension

fenoldopam

hypotension

nitroprusside

hypotension

nitroprusside

hypotension

nitroprusside

hypotension

nitroprusside

hypotension

nitroprusside

hypotension

nitroprusside

hypotension

nitroprusside

hypotension

nitroprusside

hypotension

nitroprusside

hypotension

nitroprusside

hypotension

nitroprusside

hypotension

nitroprusside

hypotension

nitroprusside

hypotension

nitroprusside

hypotension

nitroprusside

hypotension

nitroprusside

hypotension

nitroprusside

hypotension

nitroprusside

hypotension

nitroprusside

hypotension

nitroprusside

hypotension

nitroprusside

hypotension

nitroprusside

hypotension

nitroprusside

hypotension

nitroprusside

hypotension

nitroprusside

hypotension

nitroprusside

hypotension

nitroprusside

hypotension

nitroprusside

hypotension

halothane

hypotension

halothane

hypotension

halothane

hypotension

halothane

hypotension

halothane

hypotension

halothane

hypotension

halothane

hypotension


Input: Antiarrhythmic effects of optical isomers of cibenzoline on canine ventricular arrhythmias. Antiarrhythmic effects of (+) - cibenzoline and (-) - cibenzoline were examined using two canine ventricular arrhythmia models. Digitalis arrhythmia, which is suppressed by Na channel blockers, was induced by intermittent intravenous (i. v.) injection of ouabain in pentobarbital - anesthetized dogs. Adrenaline arrhythmia, which is suppressed by Ca channel blockers, was induced by adrenaline infusion in halothane - anesthetized dogs. Ten and 5 mg / kg i. v. (+) - cibenzoline suppressed digitalis - and adrenaline - induced arrhythmias, respectively. The minimum effective plasma concentrations of (+) - cibenzoline for digitalis - and adrenaline - induced arrhythmias were 1. 4 + / - 0. 4 and 2. 0 + / - 0. 6 micrograms / ml, respectively (mean + / - SD, n = 6). A lower dose of 1 mg / kg i. v. of (-) - cibenzoline suppressed the digitalis - induced arrhythmia, whereas 5 mg / kg i. v. was needed to suppress adrenaline - induced arrhythmias. The minimum effective plasma concentrations of (-) - cibenzoline for digitalis - and adrenaline - induced arrhythmia were 0. 06 + / - 0. 04 and 0. 7 + / - 0. 1 micrograms / ml, respectively (mean + / - SD, n = 6). The stronger antiarrhythmic effect of (-) - cibenzoline indicates that (-) - isomer may have an effect nearly 5 - 20 times stronger in suppressing Na channels, but effects of both drugs on Ca channels may be almost equipotent.

cibenzoline

cibenzoline

cibenzoline

Digitalis

ouabain

pentobarbital

Ca

adrenaline

halothane

cibenzoline

digitalis

adrenaline

cibenzoline

digitalis

adrenaline

cibenzoline

digitalis

adrenaline

cibenzoline

digitalis

adrenaline

cibenzoline

Ca

ventricular arrhythmias

ventricular arrhythmia

arrhythmia

Adrenaline arrhythmia

arrhythmias

arrhythmias

arrhythmia

arrhythmias

arrhythmia

adrenaline

ventricular arrhythmias

adrenaline

ventricular arrhythmia

adrenaline

arrhythmia

adrenaline

Adrenaline arrhythmia

adrenaline

arrhythmias

adrenaline

arrhythmias

adrenaline

arrhythmia

adrenaline

arrhythmias

adrenaline

arrhythmia

adrenaline

ventricular arrhythmias

adrenaline

ventricular arrhythmia

adrenaline

arrhythmia

adrenaline

Adrenaline arrhythmia

adrenaline

arrhythmias

adrenaline

arrhythmias

adrenaline

arrhythmia

adrenaline

arrhythmias

adrenaline

arrhythmia

adrenaline

ventricular arrhythmias

adrenaline

ventricular arrhythmia

adrenaline

arrhythmia

adrenaline

Adrenaline arrhythmia

adrenaline

arrhythmias

adrenaline

arrhythmias

adrenaline

arrhythmia

adrenaline

arrhythmias

adrenaline

arrhythmia

adrenaline

ventricular arrhythmias

adrenaline

ventricular arrhythmia

adrenaline

arrhythmia

adrenaline

Adrenaline arrhythmia

adrenaline

arrhythmias

adrenaline

arrhythmias

adrenaline

arrhythmia

adrenaline

arrhythmias

adrenaline

arrhythmia

adrenaline

ventricular arrhythmias

adrenaline

ventricular arrhythmia

adrenaline

arrhythmia

adrenaline

Adrenaline arrhythmia

adrenaline

arrhythmias

adrenaline

arrhythmias

adrenaline

arrhythmia

adrenaline

arrhythmias

adrenaline

arrhythmia

ouabain

ventricular arrhythmias

ouabain

ventricular arrhythmia

ouabain

arrhythmia

ouabain

Adrenaline arrhythmia

ouabain

arrhythmias

ouabain

arrhythmias

ouabain

arrhythmia

ouabain

arrhythmias

ouabain

arrhythmia


Input: Effect of Hibiscus rosa sinensis on reserpine - induced neurobehavioral and biochemical alterations in rats. Effect of methanolic extract of Hibiscus rosa sinensis (100 - 300 mg / kg) was studied on reserpine - induced orofacial dyskinesia and neurochemical alterations. The rats were treated with intraperitoneal reserpine (1 mg / kg, ip) for 3 days every other day. On day 5, vacuous chewing movements and tongue protrusions were counted for 5 min. Reserpine treated rats significantly developed vacuous chewing movements and tongue protrusions however, coadministration of Hibiscus rosa sinensis roots extract (100, 200 and 300 mg / kg, per orally) attenuated the effects. Biochemical analysis of brain revealed that the reserpine treatment significantly increased lipid peroxidation and decreased levels of superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GSH), an index of oxidative stress process. Coadministration of extract significantly reduced the lipid peroxidation and reversed the decrease in brain SOD, CAT and GSH levels. The results of the present study suggested that Hibiscus rosa sinensis had a protective role against reserpine - induced orofacial dyskinesia and oxidative stress.

Hibiscus rosa sinensis

reserpine

Hibiscus rosa sinensis

reserpine

reserpine

Reserpine

Hibiscus rosa sinensis

reserpine

superoxide

glutathione

Hibiscus rosa sinensis

reserpine

dyskinesia

dyskinesia

reserpine

dyskinesia

reserpine

dyskinesia

reserpine

dyskinesia

reserpine

dyskinesia

reserpine

dyskinesia

reserpine

dyskinesia

Reserpine

dyskinesia

Reserpine

dyskinesia

reserpine

dyskinesia

reserpine

dyskinesia

reserpine

dyskinesia

reserpine

dyskinesia


Input: Comparison of aqueous and gellan ophthalmic timolol with placebo on the 24 - hour heart rate response in patients on treatment for glaucoma. PURPOSE: Topical beta - blocker treatment is routine therapy in the management of patients with glaucoma. Therapy results in systemic absorption, however, the degree of reduction of resting and peak heart rate has not been quantified. DESIGN: This trial evaluated the effect of placebo, 0. 5% aqueous timolol (timolol solution) and a 0. 5% timolol suspension that forms a gel on application to the conjunctiva (timolol gellan) on the 24 - hour heart rate in patients currently being treated for glaucoma to quantify the reduction in mean heart rate. METHODS: Forty - three Caucasian patients with primary open - angle glaucoma or ocular hypertension with a mean (+ / - SD) age of 63 (+ / - 8) years were randomized and crossed over in a double - masked manner to 14 days of treatment with placebo (morning and evening in both eyes), timolol solution (morning and evening in both eyes), or timolol gellan (morning in both eyes with placebo in the evening). On the 13th day of each period, heart rate was recorded continuously during a typical, ambulant 24 - hour period. RESULTS: Both timolol solution and timolol gellan reduced the mean 24 - hour heart rate compared with placebo (P < or =. 001), and this reduction was most pronounced during the daytime (- 7. 5% change in mean heart rate, - 5. 7 beats / min). Timolol gellan showed a numerically but not significantly smaller reduction in 24 - hour heart rate, compared with timolol solution. During the night, the mean 12 - hour heart rate on placebo and timolol gellan were both significantly less than on timolol solution; the difference between solution and gellan treatments was statistically significant (P =. 01). CONCLUSIONS: Both timolol solution and timolol gellan decrease the mean 24 - hour heart rate compared with placebo. This response was most pronounced during the active daytime period. These data quantify the modest bradycardia associated with ophthalmic beta - blocker therapy in a typical patient population on therapy for glaucoma. Although exercise performance was not assessed in this trial, reductions of this magnitude should not have substantial clinical consequences.

timolol

timolol

timolol

timolol

timolol

timolol

timolol

timolol

timolol

Timolol

timolol

timolol

timolol

timolol

timolol

glaucoma

glaucoma

glaucoma

open - angle glaucoma

ocular hypertension

bradycardia

glaucoma

timolol

bradycardia

timolol

bradycardia

timolol

bradycardia

timolol

bradycardia

timolol

bradycardia

timolol

bradycardia

timolol

bradycardia

timolol

bradycardia

timolol

bradycardia

Timolol

bradycardia

timolol

bradycardia

timolol

bradycardia

timolol

bradycardia

timolol

bradycardia

timolol

bradycardia


Input: 5 flourouracil - induced apical ballooning syndrome: a case report. The apical ballooning syndrome (ABS) is a recently described stress - mediated acute cardiac syndrome characterized by transient wall - motion abnormalities involving the apex and midventricle with hyperkinesis of the basal left ventricular (LV) segments without obstructive epicardial coronary disease. Cardiotoxicity is not an uncommon adverse effect of chemotherapeutic agents. However, there are no reports of ABS secondary to chemotherapeutic agents. We describe the case of a woman who developed the syndrome after chemotherapy for metastatic cancer. A 79 - year - old woman presented with typical ischemic chest pain, elevated cardiac enzymes with significant ST - segment abnormalities on her electrocardiogram. She underwent recent chemotherapy with fluorouracil for metastatic colorectal cancer. Echocardiography revealed a wall - motion abnormality involving the apical and periapical segments which appeared akinetic. Coronary angiography revealed no obstructive coronary lesions. The patient was stabilized with medical therapy. Four weeks later she remained completely asymptomatic. Echocardiogram revealed a normal ejection fraction and a resolution of the apical akinesis. Pathogenetic mechanisms of cardiac complications in cancer patients undergoing chemotherapy include coronary vasospasm, endothelial damage and consequent thrombus formation. In our patient, both supraphysiologic levels of plasma catecholamines and stress related neuropeptides caused by cancer diagnosis as well as chemotherapy may have contributed the development of ABS.

5 flourouracil

fluorouracil

catecholamines

apical ballooning syndrome

apical ballooning syndrome

ABS

acute cardiac syndrome

hyperkinesis

epicardial coronary disease

Cardiotoxicity

ABS

cancer

ischemic

chest pain

colorectal cancer

akinetic

akinesis

cardiac complications

cancer

coronary vasospasm

thrombus

cancer

ABS

5 flourouracil

apical ballooning syndrome

5 flourouracil

apical ballooning syndrome

5 flourouracil

ABS

5 flourouracil

ABS

5 flourouracil

ABS

fluorouracil

apical ballooning syndrome

fluorouracil

apical ballooning syndrome

fluorouracil

ABS

fluorouracil

ABS

fluorouracil

ABS

5 flourouracil

chest pain

fluorouracil

chest pain


Input: Reduction of pain during induction with target - controlled propofol and remifentanil. BACKGROUND: Pain on injection of propofol is unpleasant. We hypothesized that propofol infusion pain might be prevented by infusing remifentanil before starting the propofol infusion in a clinical setting where target - controlled infusions (TCI) of both drugs were used. A prospective, randomized, double - blind, placebo - controlled trial was performed to determine the effect - site concentration (Ce) of remifentanil to prevent the pain without producing complications. METHODS: A total of 128 patients undergoing general surgery were randomly allocated to receive normal saline (control) or remifentanil to a target Ce of 2 ng ml (- 1) (R2), 4 ng ml (- 1) (R4), or 6 ng ml (- 1) (R6) administered via TCI. After the target Ce was achieved, the infusion of propofol was started. Remifentanil - related complications were assessed during the remifentanil infusion, and pain caused by propofol was evaluated using a four - point scale during the propofol infusion. RESULTS: The incidence of pain was significantly lower in Groups R4 and R6 than in the control and R2 groups (12 / 32 and 6 / 31 vs 26 / 31 and 25 / 32, respectively, P < 0. 001). Pain was less severe in Groups R4 and R6 than in the control and R2 groups (P < 0. 001). However, both incidence and severity of pain were not different between Groups R4 and R6. No significant complications were observed during the study. CONCLUSIONS: During induction of anaesthesia with TCI of propofol and remifentanil, a significant reduction in propofol infusion pain was achieved without significant complications by prior administration of remifentanil at a target Ce of 4 ng ml (- 1).

pain

Pain

pain

pain

pain

pain

Pain

pain

pain

propofol

remifentanil

propofol

propofol

remifentanil

propofol

remifentanil

remifentanil

propofol

Remifentanil

remifentanil

propofol

propofol

propofol

remifentanil

propofol

remifentanil

propofol

pain

propofol

Pain

propofol

pain

propofol

pain

propofol

pain

propofol

pain

propofol

Pain

propofol

pain

propofol

pain

propofol

pain

propofol

Pain

propofol

pain

propofol

pain

propofol

pain

propofol

pain

propofol

Pain

propofol

pain

propofol

pain

propofol

pain

propofol

Pain

propofol

pain

propofol

pain

propofol

pain

propofol

pain

propofol

Pain

propofol

pain

propofol

pain

propofol

pain

propofol

Pain

propofol

pain

propofol

pain

propofol

pain

propofol

pain

propofol

Pain

propofol

pain

propofol

pain

propofol

pain

propofol

Pain

propofol

pain

propofol

pain

propofol

pain

propofol

pain

propofol

Pain

propofol

pain

propofol

pain

propofol

pain

propofol

Pain

propofol

pain

propofol

pain

propofol

pain

propofol

pain

propofol

Pain

propofol

pain

propofol

pain

propofol

pain

propofol

Pain

propofol

pain

propofol

pain

propofol

pain

propofol

pain

propofol

Pain

propofol

pain

propofol

pain

propofol

pain

propofol

Pain

propofol

pain

propofol

pain

propofol

pain

propofol

pain

propofol

Pain

propofol

pain

propofol

pain

propofol

pain

propofol

Pain

propofol

pain

propofol

pain

propofol

pain

propofol

pain

propofol

Pain

propofol

pain

propofol

pain


Input: Prenatal exposure to fluoxetine induces fetal pulmonary hypertension in the rat. RATIONALE: Fluoxetine is a selective serotonin reuptake inhibitor antidepressant widely used by pregnant women. Epidemiological data suggest that fluoxetine exposure prenatally increases the prevalence of persistent pulmonary hypertension syndrome of the newborn. The mechanism responsible for this effect is unclear and paradoxical, considering the current evidence of a pulmonary hypertension protective fluoxetine effect in adult rodents. OBJECTIVES: To evaluate the fluoxetine effect on fetal rat pulmonary vascular smooth muscle mechanical properties and cell proliferation rate. METHODS: Pregnant rats were treated with fluoxetine (10 mg / kg) from Day 11 through Day 21 of gestation. MEASUREMENTS AND MAIN RESULTS: Fetuses were delivered by cesarean section. As compared with controls, fluoxetine exposure resulted in fetal pulmonary hypertension as evidenced by an increase in the weight ratio of the right ventricle to the left ventricle plus septum (P = 0. 02) and by an increase in pulmonary arterial medial thickness (P < 0. 01). Postnatal mortality was increased among experimental animals, and arterial oxygen saturation was 96 + / - 1% in 1 - day - old control animals and significantly lower (P < 0. 01) in fluoxetine - exposed pups (79 + / - 2%). In vitro, fluoxetine induced pulmonary arterial muscle contraction in fetal, but not adult, animals (P < 0. 01) and reduced serotonin - induced contraction at both ages (P < 0. 01). After in utero exposure to a low fluoxetine concentration the pulmonary arterial smooth muscle cell proliferation rate was significantly increased in fetal, but not adult, cells (P < 0. 01). CONCLUSIONS: In contrast to the adult, fluoxetine exposure in utero induces pulmonary hypertension in the fetal rat as a result of a developmentally regulated increase in pulmonary vascular smooth muscle proliferation.

fluoxetine

Fluoxetine

serotonin

fluoxetine

fluoxetine

fluoxetine

fluoxetine

fluoxetine

oxygen

fluoxetine

fluoxetine

serotonin

fluoxetine

fluoxetine

fetal pulmonary hypertension

fetal pulmonary hypertension

pulmonary hypertension

pulmonary hypertension syndrome

pulmonary hypertension

fetal pulmonary hypertension

fetal pulmonary hypertension

pulmonary hypertension

pulmonary hypertension

fluoxetine

fetal pulmonary hypertension

fluoxetine

fetal pulmonary hypertension

fluoxetine

fetal pulmonary hypertension

fluoxetine

fetal pulmonary hypertension

Fluoxetine

fetal pulmonary hypertension

Fluoxetine

fetal pulmonary hypertension

Fluoxetine

fetal pulmonary hypertension

Fluoxetine

fetal pulmonary hypertension

fluoxetine

fetal pulmonary hypertension

fluoxetine

fetal pulmonary hypertension

fluoxetine

fetal pulmonary hypertension

fluoxetine

fetal pulmonary hypertension

fluoxetine

fetal pulmonary hypertension

fluoxetine

fetal pulmonary hypertension

fluoxetine

fetal pulmonary hypertension

fluoxetine

fetal pulmonary hypertension

fluoxetine

fetal pulmonary hypertension

fluoxetine

fetal pulmonary hypertension

fluoxetine

fetal pulmonary hypertension

fluoxetine

fetal pulmonary hypertension

fluoxetine

fetal pulmonary hypertension

fluoxetine

fetal pulmonary hypertension

fluoxetine

fetal pulmonary hypertension

fluoxetine

fetal pulmonary hypertension

fluoxetine

fetal pulmonary hypertension

fluoxetine

fetal pulmonary hypertension

fluoxetine

fetal pulmonary hypertension

fluoxetine

fetal pulmonary hypertension

fluoxetine

fetal pulmonary hypertension

fluoxetine

fetal pulmonary hypertension

fluoxetine

fetal pulmonary hypertension

fluoxetine

fetal pulmonary hypertension

fluoxetine

fetal pulmonary hypertension

fluoxetine

fetal pulmonary hypertension

fluoxetine

fetal pulmonary hypertension

fluoxetine

fetal pulmonary hypertension

fluoxetine

fetal pulmonary hypertension

fluoxetine

fetal pulmonary hypertension

fluoxetine

fetal pulmonary hypertension

fluoxetine

fetal pulmonary hypertension

fluoxetine

fetal pulmonary hypertension

fluoxetine

fetal pulmonary hypertension

fluoxetine

fetal pulmonary hypertension

fluoxetine

fetal pulmonary hypertension

fluoxetine

pulmonary hypertension

fluoxetine

pulmonary hypertension syndrome

fluoxetine

pulmonary hypertension

fluoxetine

pulmonary hypertension

fluoxetine

pulmonary hypertension

Fluoxetine

pulmonary hypertension

Fluoxetine

pulmonary hypertension syndrome

Fluoxetine

pulmonary hypertension

Fluoxetine

pulmonary hypertension

Fluoxetine

pulmonary hypertension

fluoxetine

pulmonary hypertension

fluoxetine

pulmonary hypertension syndrome

fluoxetine

pulmonary hypertension

fluoxetine

pulmonary hypertension

fluoxetine

pulmonary hypertension

fluoxetine

pulmonary hypertension

fluoxetine

pulmonary hypertension syndrome

fluoxetine

pulmonary hypertension

fluoxetine

pulmonary hypertension

fluoxetine

pulmonary hypertension

fluoxetine

pulmonary hypertension

fluoxetine

pulmonary hypertension syndrome

fluoxetine

pulmonary hypertension

fluoxetine

pulmonary hypertension

fluoxetine

pulmonary hypertension

fluoxetine

pulmonary hypertension

fluoxetine

pulmonary hypertension syndrome

fluoxetine

pulmonary hypertension

fluoxetine

pulmonary hypertension

fluoxetine

pulmonary hypertension

fluoxetine

pulmonary hypertension

fluoxetine

pulmonary hypertension syndrome

fluoxetine

pulmonary hypertension

fluoxetine

pulmonary hypertension

fluoxetine

pulmonary hypertension

fluoxetine

pulmonary hypertension

fluoxetine

pulmonary hypertension syndrome

fluoxetine

pulmonary hypertension

fluoxetine

pulmonary hypertension

fluoxetine

pulmonary hypertension

fluoxetine

pulmonary hypertension

fluoxetine

pulmonary hypertension syndrome

fluoxetine

pulmonary hypertension

fluoxetine

pulmonary hypertension

fluoxetine

pulmonary hypertension

fluoxetine

pulmonary hypertension

fluoxetine

pulmonary hypertension syndrome

fluoxetine

pulmonary hypertension

fluoxetine

pulmonary hypertension

fluoxetine

pulmonary hypertension

fluoxetine

pulmonary hypertension

fluoxetine

pulmonary hypertension syndrome

fluoxetine

pulmonary hypertension

fluoxetine

pulmonary hypertension

fluoxetine

pulmonary hypertension


Input: Syncope and QT prolongation among patients treated with methadone for heroin dependence in the city of Copenhagen. BACKGROUND: Methadone is prescribed to heroin addicts to decrease illicit opioid use. Prolongation of the QT interval in the ECG of patients with torsade de pointes (TdP) has been reported in methadone users. As heroin addicts sometimes faint while using illicit drugs, doctors might attribute too many episodes of syncope to illicit drug use and thereby underestimate the incidence of TdP in this special population, and the high mortality in this population may, in part, be caused by the proarrhythmic effect of methadone. METHODS: In this cross - sectional study interview, ECGs and blood samples were collected in a population of adult heroin addicts treated with methadone or buprenorphine on a daily basis. Of the patients at the Drug Addiction Service in the municipal of Copenhagen, 450 (approximately 52%) were included. The QT interval was estimated from 12 lead ECGs. All participants were interviewed about any experience of syncope. The association between opioid dose and QT, and methadone dose and reporting of syncope was assessed using multivariate linear regression and logistic regression, respectively. RESULTS: Methadone dose was associated with longer QT interval of 0. 140 ms / mg (p = 0. 002). No association between buprenorphine and QTc was found. Among the subjects treated with methadone, 28% men and 32% women had prolonged QTc interval. None of the subjects treated with buprenorphine had QTc interval > 0. 440 s ((1 / 2)). A 50 mg higher methadone dose was associated with a 1. 2 (95% CI 1. 1 to 1. 4) times higher odds for syncope. CONCLUSIONS: Methadone is associated with QT prolongation and higher reporting of syncope in a population of heroin addicts.

Syncope

QT prolongation

torsade de pointes

TdP

syncope

TdP

syncope

syncope

prolonged QTc interval

syncope

QT prolongation

syncope

methadone

heroin

Methadone

heroin

methadone

heroin

methadone

heroin

methadone

buprenorphine

methadone

Methadone

buprenorphine

methadone

buprenorphine

methadone

Methadone

heroin

methadone

QT prolongation

methadone

prolonged QTc interval

methadone

QT prolongation

Methadone

QT prolongation

Methadone

prolonged QTc interval

Methadone

QT prolongation

methadone

QT prolongation

methadone

prolonged QTc interval

methadone

QT prolongation

methadone

QT prolongation

methadone

prolonged QTc interval

methadone

QT prolongation

methadone

QT prolongation

methadone

prolonged QTc interval

methadone

QT prolongation

methadone

QT prolongation

methadone

prolonged QTc interval

methadone

QT prolongation

Methadone

QT prolongation

Methadone

prolonged QTc interval

Methadone

QT prolongation

methadone

QT prolongation

methadone

prolonged QTc interval

methadone

QT prolongation

methadone

QT prolongation

methadone

prolonged QTc interval

methadone

QT prolongation

Methadone

QT prolongation

Methadone

prolonged QTc interval

Methadone

QT prolongation

methadone

Syncope

methadone

syncope

methadone

syncope

methadone

syncope

methadone

syncope

methadone

syncope

Methadone

Syncope

Methadone

syncope

Methadone

syncope

Methadone

syncope

Methadone

syncope

Methadone

syncope

methadone

Syncope

methadone

syncope

methadone

syncope

methadone

syncope

methadone

syncope

methadone

syncope

methadone

Syncope

methadone

syncope

methadone

syncope

methadone

syncope

methadone

syncope

methadone

syncope

methadone

Syncope

methadone

syncope

methadone

syncope

methadone

syncope

methadone

syncope

methadone

syncope

methadone

Syncope

methadone

syncope

methadone

syncope

methadone

syncope

methadone

syncope

methadone

syncope

Methadone

Syncope

Methadone

syncope

Methadone

syncope

Methadone

syncope

Methadone

syncope

Methadone

syncope

methadone

Syncope

methadone

syncope

methadone

syncope

methadone

syncope

methadone

syncope

methadone

syncope

methadone

Syncope

methadone

syncope

methadone

syncope

methadone

syncope

methadone

syncope

methadone

syncope

Methadone

Syncope

Methadone

syncope

Methadone

syncope

Methadone

syncope

Methadone

syncope

Methadone

syncope


Input: Peripheral neuropathy caused by high - dose cytosine arabinoside treatment in a patient with acute myeloid leukemia. The central nervous system toxicity of high - dose cytosine arabinoside is well recognized, but the toxicity of cytosine arabinoside in the peripheral nervous system has been infrequently reported. A 49 - year - old Japanese man was diagnosed with acute myeloid leukemia. After he achieved complete remission, he received high - dose cytosine arabinoside treatment (2 g / m2 twice a day for 5 days; total, 20 g / m2) as consolidation therapy. The first course of high - dose cytosine arabinoside resulted in no unusual symptoms, but on day 21 of the second course of treatment, the patient complained of numbness in his right foot. Electromyogram and nerve - conduction studies showed peripheral neuropathy in both peroneal nerves. This neuropathy was gradually resolving; however, after the patient received allogeneic bone marrow transplantation, the symptoms worsened, with the development of graft - versus - host disease, and the symptoms subsequently responded to methylprednisolone. Although the mechanisms of peripheral neuropathy are still unclear, high - dose cytosine arabinoside is a therapy that is potentially toxic to the peripheral nervous system, and auto / alloimmunity may play an important role in these mechanisms.

Peripheral neuropathy

acute myeloid leukemia

toxicity

toxicity

acute myeloid leukemia

numbness

peripheral neuropathy

neuropathy

graft - versus - host disease

peripheral neuropathy

cytosine arabinoside

cytosine arabinoside

cytosine arabinoside

cytosine arabinoside

cytosine arabinoside

methylprednisolone

cytosine arabinoside

cytosine arabinoside

Peripheral neuropathy

cytosine arabinoside

peripheral neuropathy

cytosine arabinoside

peripheral neuropathy

cytosine arabinoside

Peripheral neuropathy

cytosine arabinoside

peripheral neuropathy

cytosine arabinoside

peripheral neuropathy

cytosine arabinoside

Peripheral neuropathy

cytosine arabinoside

peripheral neuropathy

cytosine arabinoside

peripheral neuropathy

cytosine arabinoside

Peripheral neuropathy

cytosine arabinoside

peripheral neuropathy

cytosine arabinoside

peripheral neuropathy

cytosine arabinoside

Peripheral neuropathy

cytosine arabinoside

peripheral neuropathy

cytosine arabinoside

peripheral neuropathy

cytosine arabinoside

Peripheral neuropathy

cytosine arabinoside

peripheral neuropathy

cytosine arabinoside

peripheral neuropathy


Input: Atorvastatin prevented and reversed dexamethasone - induced hypertension in the rat. To assess the antioxidant effects of atorvastatin (atorva) on dexamethasone (dex) - induced hypertension, 60 male Sprague - Dawley rats were treated with atorva 30 mg / kg / day or tap water for 15 days. Dex increased systolic blood pressure (SBP) from 109 + / - 1. 8 to 135 + / - 0. 6 mmHg and plasma superoxide (5711 + / - 284. 9 saline, 7931 + / - 392. 8 U / ml dex, P < 0. 001). In this prevention study, SBP in the atorva + dex group was increased from 115 + / - 0. 4 to 124 + / - 1. 5 mmHg, but this was significantly lower than in the dex - only group (P' < 0. 05). Atorva reversed dex - induced hypertension (129 + / - 0. 6 mmHg, vs. 135 + / - 0. 6 mmHg P' < 0. 05) and decreased plasma superoxide (7931 + / - 392. 8 dex, 1187 + / - 441. 2 atorva + dex, P < 0. 0001). Plasma nitrate / nitrite (NOx) was decreased in dex - treated rats compared to saline - treated rats (11. 2 + / - 1. 08 microm, 15. 3 + / - 1. 17 microm, respectively, P < 0. 05). Atorva affected neither plasma NOx nor thymus weight. Thus, atorvastatin prevented and reversed dexamethasone - induced hypertension in the rat.

Atorvastatin

dexamethasone

atorvastatin

atorva

dexamethasone

dex

atorva

Dex

superoxide

dex

atorva

dex

dex

Atorva

dex

superoxide

dex

atorva

dex

nitrate

nitrite

dex

Atorva

atorvastatin

dexamethasone

hypertension

hypertension

hypertension

hypertension

dexamethasone

hypertension

dexamethasone

hypertension

dexamethasone

hypertension

dexamethasone

hypertension

dexamethasone

hypertension

dexamethasone

hypertension

dexamethasone

hypertension

dexamethasone

hypertension

dex

hypertension

dex

hypertension

dex

hypertension

dex

hypertension

Dex

hypertension

Dex

hypertension

Dex

hypertension

Dex

hypertension

dex

hypertension

dex

hypertension

dex

hypertension

dex

hypertension

dex

hypertension

dex

hypertension

dex

hypertension

dex

hypertension

dex

hypertension

dex

hypertension

dex

hypertension

dex

hypertension

dex

hypertension

dex

hypertension

dex

hypertension

dex

hypertension

dex

hypertension

dex

hypertension

dex

hypertension

dex

hypertension

dex

hypertension

dex

hypertension

dex

hypertension

dex

hypertension

dex

hypertension

dex

hypertension

dex

hypertension

dex

hypertension

dexamethasone

hypertension

dexamethasone

hypertension

dexamethasone

hypertension

dexamethasone

hypertension


Input: Two prodrugs of potent and selective GluR5 kainate receptor antagonists actives in three animal models of pain. Amino acids 5 and 7, two potent and selective competitive GluR5 KA receptor antagonists, exhibited high GluR5 receptor affinity over other glutamate receptors. Their ester prodrugs 6 and 8 were orally active in three models of pain: reversal of formalin - induced paw licking, carrageenan - induced thermal hyperalgesia, and capsaicin - induced mechanical hyperalgesia.

kainate

KA

glutamate

formalin

carrageenan

capsaicin

pain

pain

thermal hyperalgesia

mechanical hyperalgesia

carrageenan

thermal hyperalgesia

carrageenan

mechanical hyperalgesia

capsaicin

thermal hyperalgesia

capsaicin

mechanical hyperalgesia


Input: Sirolimus and mycophenolate mofetil for calcineurin - free immunosuppression in renal transplant recipients. Calcineurin inhibitors, such as cyclosporine and tacrolimus, have been available for almost 20 years. Although these drugs are highly effective and represent the mainstay of transplant immunosuppression, they are associated with acute and chronic nephrotoxicity. Acute nephrotoxicity, which occurs in the early period after transplantation, leads to a higher rate of dialysis, and chronic nephrotoxicity may eventually result in graft loss. Acute and chronic nephrotoxicity is becoming more common as the use of marginal kidneys for transplantation increases. Two recently available immunosuppressive agents, mycophenolate mofetil and sirolimus (rapamycin), have no nephrotoxicity. The use of these drugs in combination with other agents has led to the development of new paradigms of immunosuppressive therapy. This paper reviews the results of clinical trials that have investigated these new approaches to immunosuppression in renal transplant recipients.

Sirolimus

mycophenolate mofetil

cyclosporine

tacrolimus

mycophenolate mofetil

sirolimus

rapamycin

nephrotoxicity

nephrotoxicity

nephrotoxicity

nephrotoxicity

nephrotoxicity

tacrolimus

nephrotoxicity

tacrolimus

nephrotoxicity

tacrolimus

nephrotoxicity

tacrolimus

nephrotoxicity

tacrolimus

nephrotoxicity

cyclosporine

nephrotoxicity

cyclosporine

nephrotoxicity

cyclosporine

nephrotoxicity

cyclosporine

nephrotoxicity

cyclosporine

nephrotoxicity


Input: Erythropoietin restores the anemia - induced reduction in cyclophosphamide cytotoxicity in rat tumors. The aim of this study was to examine the impact of anemia prevention by recombinant human erythropoietin (rHuEPO) treatment on the cytotoxicity of cyclophosphamide in solid experimental tumors. Anemia was induced using a single dose of carboplatin (50 mg / kg i. v.) resulting in a long - lasting reduction (30%) of the hemoglobin concentration. In a second group, the development of anemia was prevented by rHuEPO (1000 IU / kg) administered s. c. three times / week starting 7 days before carboplatin application. Four days after carboplatin treatment, tumors (DS - sarcoma of the rat) were implanted s. c. onto the hind food dorsum. Neither carboplatin nor rHuEPO treatment influenced tumor growth rate per se. When tumors were treated with a single dose of cyclophosphamide (60 mg / kg i. p.) 5 days after implantation, a growth delay with a subsequent regrowth of the tumors was observed. In the anemia group, the growth delay was significantly shorter compared with nonanemic controls (13. 3 days versus 8. 6 days). In the group where anemia was prevented by rHuEPO treatment, growth delay was comparable with that of nonanemic controls (13. 3 days). These results suggest that chemotherapy - induced anemia reduces cytotoxicity of cyclophosphamide in tumors, whereas correction of anemia by rHuEPO treatment (epoetin alpha) increases the sensitivity, probably as a result of an improved oxygen supply to tumor tissue.

anemia

cytotoxicity

tumors

anemia

cytotoxicity

tumors

Anemia

anemia

tumors

sarcoma

tumor

tumors

tumors

anemia

anemia

anemia

cytotoxicity

tumors

anemia

tumor

cyclophosphamide

cyclophosphamide

carboplatin

carboplatin

carboplatin

carboplatin

cyclophosphamide

cyclophosphamide

oxygen

carboplatin

anemia

carboplatin

anemia

carboplatin

Anemia

carboplatin

anemia

carboplatin

anemia

carboplatin

anemia

carboplatin

anemia

carboplatin

anemia

carboplatin

anemia

carboplatin

anemia

carboplatin

Anemia

carboplatin

anemia

carboplatin

anemia

carboplatin

anemia

carboplatin

anemia

carboplatin

anemia

carboplatin

anemia

carboplatin

anemia

carboplatin

Anemia

carboplatin

anemia

carboplatin

anemia

carboplatin

anemia

carboplatin

anemia

carboplatin

anemia

carboplatin

anemia

carboplatin

anemia

carboplatin

Anemia

carboplatin

anemia

carboplatin

anemia

carboplatin

anemia

carboplatin

anemia

carboplatin

anemia


Input: The role of nitrergic system in lidocaine - induced convulsion in the mouse. The effects of N - nitro - L - arginine - methyl ester (L - NAME) a nitric oxide (NO) synthase inhibitor and L - arginine, a NO precursor, were investigated on lidocaine - induced convulsions. In the first experiment, four groups of mice received physiological saline (0. 9%), L - arginine (300 mg / kg, i. p.), L - NAME (100 mg / kg, i. p.) and diazepam (2 mg / kg), respectively. Thirty minutes after these injections, all mice received lidocaine (50 mg / kg, i. p.). In the second experiment, four groups of mice received similar treatment in the first experiment, and 30 min after these injections, all mice received a higher dose of lidocaine (80 mg / kg). L - NAME (100 mg / kg, i. p.) and diazepam (2 mg / kg) significantly decreased the incidence of lidocaine (50 mg / kg) - induced convulsions. In contrast, the L - arginine treatment increased the incidence of lidocaine (80 mg / kg, i. p.) - induced convulsions significantly. These results may suggest that NO is a proconvulsant mediator in lidocaine - induced convulsions.

lidocaine

N - nitro - L - arginine - methyl ester

L - NAME

nitric oxide

NO

L - arginine

NO

lidocaine

L - arginine

L - NAME

diazepam

lidocaine

lidocaine

L - NAME

diazepam

lidocaine

L - arginine

lidocaine

NO

lidocaine

convulsion

convulsions

convulsions

convulsions

convulsions

lidocaine

convulsion

lidocaine

convulsions

lidocaine

convulsions

lidocaine

convulsions

lidocaine

convulsions

lidocaine

convulsion

lidocaine

convulsions

lidocaine

convulsions

lidocaine

convulsions

lidocaine

convulsions

lidocaine

convulsion

lidocaine

convulsions

lidocaine

convulsions

lidocaine

convulsions

lidocaine

convulsions

lidocaine

convulsion

lidocaine

convulsions

lidocaine

convulsions

lidocaine

convulsions

lidocaine

convulsions

lidocaine

convulsion

lidocaine

convulsions

lidocaine

convulsions

lidocaine

convulsions

lidocaine

convulsions

lidocaine

convulsion

lidocaine

convulsions

lidocaine

convulsions

lidocaine

convulsions

lidocaine

convulsions

lidocaine

convulsion

lidocaine

convulsions

lidocaine

convulsions

lidocaine

convulsions

lidocaine

convulsions


Input: Effect of intravenous metoprolol or intravenous metoprolol plus glucagon on dobutamine - induced myocardial ischemia. STUDY OBJECTIVE: To determine the effect of metoprolol on dobutamine stress testing with technetium - 99m sestamibi single - photon emission computed tomography imaging and ST - segment monitoring, and to assess the impact of intravenous glucagon on metoprolol' s effects. DESIGN: Randomized, double - blind, placebo - controlled trial. SETTING: Community hospital. PATIENTS: Twenty - two patients with known reversible perfusion defects. INTERVENTION: Patients underwent dobutamine stress tests per standard protocol. Before dobutamine was begun, no therapy was given during the first visit, and patients were randomized on subsequent visits to receive metoprolol or metoprolol plus glucagon 1 mg. Metoprolol was dosed to achieve a resting predobutamine heart rate below 65 beats / minute or a total intravenous dose of 20 mg. MEASUREMENTS AND MAIN RESULTS: Metoprolol reduced maximum heart rate 31%, summed stress scores 29%, and summed difference scores 43% versus control. Metoprolol plus glucagon also reduced the maximum heart rate 29% versus control. Summed stress and summed difference scores were not significantly reduced, although they were 18% and 30% lower, respectively, than control. No significant differences were found in any parameter between metoprolol and metoprolol - glucagon. CONCLUSION: During dobutamine stress testing, metoprolol attenuates or eliminates evidence of myocardial ischemia. Glucagon 1 mg, although somewhat effective, does not correct this effect to the extent that it can be administered clinically.

metoprolol

metoprolol

dobutamine

metoprolol

dobutamine

technetium - 99m sestamibi

metoprolol

dobutamine

dobutamine

metoprolol

metoprolol

Metoprolol

predobutamine

Metoprolol

Metoprolol

metoprolol

metoprolol

dobutamine

metoprolol

myocardial ischemia

myocardial ischemia

dobutamine

myocardial ischemia

dobutamine

myocardial ischemia

dobutamine

myocardial ischemia

dobutamine

myocardial ischemia

dobutamine

myocardial ischemia

dobutamine

myocardial ischemia

dobutamine

myocardial ischemia

dobutamine

myocardial ischemia

dobutamine

myocardial ischemia

dobutamine

myocardial ischemia


Input: Prednisolone - induced muscle dysfunction is caused more by atrophy than by altered acetylcholine receptor expression. Large doses of glucocorticoids can alter muscle physiology and susceptibility to neuromuscular blocking drugs by mechanisms not clearly understood. We investigated the effects of moderate and large doses of prednisolone on muscle function and pharmacology, and their relationship to changes in muscle size and acetylcholine receptor (AChR) expression. With institutional approval, 35 Sprague - Dawley rats were randomly allocated to receive daily subcutaneous doses of 10 mg / kg prednisolone (P10 group), 100 mg / kg prednisolone (P100 group), or an equal volume of saline (S group) for 7 days. A fourth group of rats was pair fed (food restricted) with the P100 rats for 7 days (FR group). On Day 8, the nerve - evoked peak twitch tensions, tetanic tensions, and fatigability, and the dose - response curves of d - tubocurarine in the tibialis cranialis muscle were measured in vivo and related to muscle mass or expression of AChRs. Rate of body weight gain was depressed in the P100, FR, and P10 groups compared with the S group. Tibialis muscle mass was smaller in the P100 group than in the P10 or S groups. The evoked peak twitch and tetanic tensions were less in the P100 group than in the P10 or S groups, however, tension per milligram of muscle mass was greater in the P100 group than in the S group. The 50% effective dose of d - tubocurarine (microg / kg) in the tibialis muscle was smaller in the P10 (33. 6 + / - 5. 4) than in the S (61. 9 + / - 5. 0) or the P100 (71. 3 + / - 9. 6) groups. AChR expression was less in the P10 group than in the S group. The evoked tensions correlated with muscle mass (r (2) = 0. 32, P < 0. 001), however, not with expression of AChR. The 50% effective dose of d - tubocurarine did not correlate with muscle mass or AChR expression. Our results suggest that the neuromuscular dysfunction after prednisolone is dose - dependent, and derives primarily from muscle atrophy and derives less so from changes in AChR expression. IMPLICATIONS: The mechanisms by which chronic glucocorticoid therapy alters neuromuscular physiology and pharmacology are unclear. We suggest that the observed effects are dose - dependent and derive primarily from muscle atrophy and derive less from changes in acetylcholine receptor expression.

Prednisolone

acetylcholine

prednisolone

acetylcholine

prednisolone

prednisolone

d - tubocurarine

d - tubocurarine

d - tubocurarine

prednisolone

acetylcholine

muscle dysfunction

atrophy

tetanic

tetanic

neuromuscular dysfunction

muscle atrophy

muscle atrophy

Prednisolone

muscle dysfunction

prednisolone

muscle dysfunction

prednisolone

muscle dysfunction

prednisolone

muscle dysfunction

prednisolone

muscle dysfunction

Prednisolone

muscle atrophy

Prednisolone

muscle atrophy

prednisolone

muscle atrophy

prednisolone

muscle atrophy

prednisolone

muscle atrophy

prednisolone

muscle atrophy

prednisolone

muscle atrophy

prednisolone

muscle atrophy

prednisolone

muscle atrophy

prednisolone

muscle atrophy


Input: Rapid reversal of life - threatening diltiazem - induced tetany with calcium chloride. We describe a patient who developed tetany with sudden respiratory arrest after the infusion of intravenous diltiazem. The administration of calcium chloride rapidly resolved the patient' s tetany with prompt recovery of respiratory function, averting the need for more aggressive airway management and ventilatory support. The emergency physician should be aware that life - threatening tetany may accompany the administration of intravenous diltiazem and that calcium chloride may be a rapid and effective remedy.

diltiazem

calcium chloride

diltiazem

calcium chloride

diltiazem

calcium chloride

tetany

tetany

respiratory arrest

tetany

tetany

diltiazem

tetany

diltiazem

tetany

diltiazem

tetany

diltiazem

tetany

diltiazem

tetany

diltiazem

tetany

diltiazem

tetany

diltiazem

tetany

diltiazem

tetany

diltiazem

tetany

diltiazem

tetany

diltiazem

tetany


Input: Effects of nonsteroidal anti - inflammatory drugs on hemostasis in patients with aneurysmal subarachnoid hemorrhage. Platelet function is impaired by nonsteroidal anti - inflammatory drugs (NSAIDs) with prominent anti - inflammatory properties. Their safety in patients undergoing intracranial surgery is under debate. Patients with aneurysmal subarachnoid hemorrhage (SAH) were randomized to receive either ketoprofen, 100 mg, three times a day (ketoprofen group, n = 9) or a weak NSAID, acetaminophen, 1 g, three times a day (acetaminophen group, n = 9) starting immediately after the diagnosis of aneurysmal SAH. Treatment was continued for 3 days postoperatively. Test blood samples were taken before treatment and surgery as well as on the first, third, and fifth postoperative mornings. Maximal platelet aggregation induced by 6 microM of adenosine diphosphate decreased after administration of ketoprofen. Aggregation was lower (P <. 05) in the ketoprofen group than in the acetaminophen group just before surgery and on the third postoperative day. In contrast, maximal platelet aggregation increased in the acetaminophen group on the third postoperative day as compared with the pretreatment platelet aggregation results (P <. 05). One patient in the ketoprofen group developed a postoperative intracranial hematoma. Coagulation (prothrombin time [PT], activated partial thromboplastin time [APPT], fibrinogen concentration, and antithrombin III [AT III]) was comparable between the two groups. Ketoprofen but not acetaminophen impaired platelet function in patients with SAH. If ketoprofen is used before surgery on cerebral artery aneurysms, it may pose an additional risk factor for hemorrhage.

aneurysmal subarachnoid hemorrhage

aneurysmal subarachnoid hemorrhage

SAH

aneurysmal

SAH

platelet aggregation

platelet aggregation

platelet aggregation

hematoma

SAH

artery aneurysms

hemorrhage

ketoprofen

ketoprofen

acetaminophen

acetaminophen

adenosine diphosphate

ketoprofen

ketoprofen

acetaminophen

acetaminophen

ketoprofen

Ketoprofen

acetaminophen

ketoprofen

ketoprofen

hematoma

ketoprofen

hematoma

ketoprofen

hematoma

ketoprofen

hematoma

ketoprofen

hematoma

Ketoprofen

hematoma

ketoprofen

hematoma

ketoprofen

platelet aggregation

ketoprofen

platelet aggregation

ketoprofen

platelet aggregation

ketoprofen

platelet aggregation

ketoprofen

platelet aggregation

ketoprofen

platelet aggregation

ketoprofen

platelet aggregation

ketoprofen

platelet aggregation

ketoprofen

platelet aggregation

ketoprofen

platelet aggregation

ketoprofen

platelet aggregation

ketoprofen

platelet aggregation

ketoprofen

platelet aggregation

ketoprofen

platelet aggregation

ketoprofen

platelet aggregation

Ketoprofen

platelet aggregation

Ketoprofen

platelet aggregation

Ketoprofen

platelet aggregation

ketoprofen

platelet aggregation

ketoprofen

platelet aggregation

ketoprofen

platelet aggregation


Input: Value of methylprednisolone in prevention of the arthralgia - myalgia syndrome associated with the total dose infusion of iron dextran: a double blind randomized trial. The safety and efficacy of total dose infusion (TDI) of iron dextran has been well documented. In 40% of treated patients, an arthralgia - myalgia syndrome develops. The purpose of this randomized, double - blind, prospective study was to investigate whether intravenous (i. v.) administration of methylprednisolone (MP) prevents this complication. Sixty - five patients, 34 women and 31 men, ages 36 to 80 years, received either normal saline before and after TDI (group 1), 125 mg i. v. MP before and saline after TDI (group 2), or 125 mg i. v. MP before and after TDI (group 3). Patients were observed for 72 hours and reactions were recorded and graded according to severity. Fifty - eight percent of group 1 patients, 33% of group 2, and 26% of group 3 had reactions to TDI. The severity of reactions (minimal, mild, and moderate, respectively) was as follows: group 1 - - 6, 6, and 2; group 2 - - 1, 5, and 0; group 3 - - 5, 1, and 0. Data were analyzed by the two - sided Fisher' s exact test using 95% confidence intervals with the approximation of Woolf. These data demonstrate that administration of MP before and after TDI reduces the frequency and severity of the arthralgia - myalgia syndrome. We conclude that 125 mg i. v. MP should be given routinely before and after TDI of iron dextran.

methylprednisolone

iron dextran

iron dextran

methylprednisolone

MP

MP

MP

MP

MP

iron dextran

arthralgia

myalgia

arthralgia

myalgia

arthralgia

myalgia

iron dextran

arthralgia

iron dextran

arthralgia

iron dextran

arthralgia

iron dextran

arthralgia

iron dextran

arthralgia

iron dextran

arthralgia

iron dextran

arthralgia

iron dextran

arthralgia

iron dextran

arthralgia


Input: Long - term effects of vincristine on the peripheral nervous system. Forty patients with Non - Hodgkin' s Lymphoma treated with vincristine between 1984 and 1990 (cumulative dose 12 mg in 18 - 24 weeks) were investigated in order to evaluate the long term effects of vincristine on the peripheral nervous system. The patients were interviewed with emphasis on neuropathic symptoms. Physical and quantitative sensory examination with determination of vibratory perception and thermal discrimination thresholds were performed, four to 77 months (median 34 months) after vincristine treatment. Twenty - seven patients reported neuropathic symptoms. In 13 of these 27 patients symptoms were still present at the time of examination. In these patients sensory signs and symptoms predominated. In the other 14 patients symptoms had been present in the past. Symptoms persisted maximally 40 months since cessation of therapy. There was no age difference between patients with and without complaints at the time of examination. Normal reflexes were found in two third of patients. Neuropathic complaints were not very troublesome on the long term. It is concluded that with the above mentioned vincristine dose schedule signs and symptoms of vincristine neuropathy are reversible for a great deal and prognosis is fairly good.

vincristine

vincristine

vincristine

vincristine

vincristine

vincristine

Non - Hodgkin' s Lymphoma

neuropathic symptoms

neuropathic symptoms

neuropathy

vincristine

neuropathic symptoms

vincristine

neuropathic symptoms

vincristine

neuropathic symptoms

vincristine

neuropathic symptoms

vincristine

neuropathic symptoms

vincristine

neuropathic symptoms

vincristine

neuropathic symptoms

vincristine

neuropathic symptoms

vincristine

neuropathic symptoms

vincristine

neuropathic symptoms

vincristine

neuropathic symptoms

vincristine

neuropathic symptoms


Input: A case of polymyositis in a patient with primary biliary cirrhosis treated with D - penicillamine. Although D - penicillamine has been used for many rheumatologic diseases, toxicity limits its usefulness in many patients. Polymyositis / dermatomyositis can develop as one of the autoimmune complications of D - penicillamine treatment, but its exact pathogenesis remains unclear. We report a patient with primary biliary cirrhosis, who developed polymyositis while receiving D - penicillamine therapy. We described the special clinical course of the patient. Patients receiving D - penicillamine therapy should be followed carefully for the development of autoimmune complications like polymyositis / dermatomyositis.

polymyositis

primary biliary cirrhosis

rheumatologic diseases

toxicity

Polymyositis

dermatomyositis

primary biliary cirrhosis

polymyositis

polymyositis

dermatomyositis

D - penicillamine

D - penicillamine

D - penicillamine

D - penicillamine

D - penicillamine

D - penicillamine

polymyositis

D - penicillamine

Polymyositis

D - penicillamine

polymyositis

D - penicillamine

polymyositis

D - penicillamine

polymyositis

D - penicillamine

Polymyositis

D - penicillamine

polymyositis

D - penicillamine

polymyositis

D - penicillamine

polymyositis

D - penicillamine

Polymyositis

D - penicillamine

polymyositis

D - penicillamine

polymyositis

D - penicillamine

polymyositis

D - penicillamine

Polymyositis

D - penicillamine

polymyositis

D - penicillamine

polymyositis

D - penicillamine

polymyositis

D - penicillamine

Polymyositis

D - penicillamine

polymyositis

D - penicillamine

polymyositis


Input: Photodistributed nifedipine - induced facial telangiectasia. Five months after starting nifedipine (Adalat), two patients developed photodistributed facial telangiectasia, which became more noticeable with time. Neither patient complained of photosensitivity or flushing. Both patients reported a significant cosmetic improvement after discontinuing the drug. One commenced the closely related drug amlodipine 3 years later, with recurrence of telangiectasia. The photodistribution of the telangiectasia suggests a significant drug / light interaction.

nifedipine

nifedipine

Adalat

amlodipine

telangiectasia

telangiectasia

flushing

telangiectasia

telangiectasia

nifedipine

telangiectasia

nifedipine

telangiectasia

nifedipine

telangiectasia

nifedipine

telangiectasia

nifedipine

telangiectasia

nifedipine

telangiectasia

nifedipine

telangiectasia

nifedipine

telangiectasia

Adalat

telangiectasia

Adalat

telangiectasia

Adalat

telangiectasia

Adalat

telangiectasia

amlodipine

telangiectasia

amlodipine

telangiectasia

amlodipine

telangiectasia

amlodipine

telangiectasia


Input: Nephrotoxicity of cyclosporin A and FK506: inhibition of calcineurin phosphatase. Cyclosporin A (CsA; 50 mg / kg) and Fujimycine (FK506; 5 mg / kg), but not the related macrolide immunosuppressant rapamycin (5 mg / kg), caused a reduction of glomerular filtration rate, degenerative changes of proximal tubular epithelium, and hypertrophy of the juxtaglomerular apparatus in male Wistar rats when given for 10 days. The molecular mechanisms of CsA and FK506 toxicity were investigated. Cyclophilin A and FK506 - binding protein, the main intracytoplasmic receptors for CsA and FK506, respectively, were each detected in renal tissue extract. In the kidney, high levels of immunoreactive and enzymatically active calcineurin were found which were inhibited by the immunosuppressants CsA and FK506, but not by rapamycin. Finally, specific immunophilin - drug - calcineurin complexes formed only in the presence of CsA and FK506, but not rapamycin. These results suggest that the nephrotoxic effects of CsA and FK506 is likely mediated through binding to renal immunophilin and inhibiting calcineurin phosphatase.

Nephrotoxicity

hypertrophy

toxicity

nephrotoxic

cyclosporin A

Cyclosporin A

CsA

Fujimycine

macrolide

rapamycin

CsA

CsA

CsA

rapamycin

CsA

rapamycin

CsA

cyclosporin A

Nephrotoxicity

cyclosporin A

nephrotoxic

Cyclosporin A

Nephrotoxicity

Cyclosporin A

nephrotoxic

CsA

Nephrotoxicity

CsA

nephrotoxic

CsA

Nephrotoxicity

CsA

nephrotoxic

CsA

Nephrotoxicity

CsA

nephrotoxic

CsA

Nephrotoxicity

CsA

nephrotoxic

CsA

Nephrotoxicity

CsA

nephrotoxic

CsA

Nephrotoxicity

CsA

nephrotoxic

Nephrotoxicity

nephrotoxic

Fujimycine

Nephrotoxicity

Fujimycine

nephrotoxic

Nephrotoxicity

nephrotoxic

Nephrotoxicity

nephrotoxic

Nephrotoxicity

nephrotoxic

Nephrotoxicity

nephrotoxic

Nephrotoxicity

nephrotoxic

Nephrotoxicity

nephrotoxic

Nephrotoxicity

nephrotoxic


Input: Massive cerebral edema associated with fulminant hepatic failure in acetaminophen overdose: possible role of cranial decompression. Cerebral edema may complicate the course of fulminant hepatic failure. Response to conventional therapy has been disappointing. We present a patient with fatal acetaminophen - induced fulminant hepatic failure, with signs and symptoms of cerebral edema, unresponsive to conventional medical therapy. Cranial decompression was carried out. A justification of the need for further evaluation of cranial decompression in such patients is presented.

cerebral edema

hepatic failure

overdose

Cerebral edema

fulminant hepatic failure

fulminant hepatic failure

cerebral edema

acetaminophen

acetaminophen

acetaminophen

cerebral edema

acetaminophen

Cerebral edema

acetaminophen

cerebral edema

acetaminophen

cerebral edema

acetaminophen

Cerebral edema

acetaminophen

cerebral edema

acetaminophen

hepatic failure

acetaminophen

fulminant hepatic failure

acetaminophen

fulminant hepatic failure

acetaminophen

hepatic failure

acetaminophen

fulminant hepatic failure

acetaminophen

fulminant hepatic failure


Input: Gentamicin nephropathy in a neonate. The clinical and autopsy findings in a premature baby who died of acute renal failure after therapy with gentamicin (5 mg / kg / day) and penicillin are presented. The serum gentamicin concentration had reached toxic levels when anuria developed. Numerous periodic acid Schiff (PAS) positive, diastase resistant cytoplasmic inclusion bodies which appeared as myelin figures in cytosegresomes under the electron microscope were identified in the proximal convoluted tubules. The pathological changes induced by gentamicin in the human neonatal kidneys have not been previously reported.

Gentamicin

gentamicin

penicillin

gentamicin

periodic acid

gentamicin

nephropathy

acute renal failure

anuria

Gentamicin

acute renal failure

gentamicin

acute renal failure

gentamicin

acute renal failure

gentamicin

acute renal failure


Input: Anti - carcinogenic action of phenobarbital given simultaneously with diethylnitrosamine in the rat. The present work has been planned in order to elucidate the effect of phenobarbital (PB: 15 mg per rat of ingested dose) on carcinogenesis when it is administered simultaneously with diethylnitrosamine (DEN: 10 mg / kg / day). Wistar rats (180 g) were treated by DEN alone or by DEN + PB during 2, 4 and 6 weeks according to our schedule for hepatocarcinogenesis. After the end of the treatment, the number and the size of induced PAS positive preneoplastic foci was significantly reduced when PB was given simultaneously with DEN for 4 and 6 weeks. The mitotic inhibition and the production of micronuclei normally observed after partial hepatectomy in DEN treated rats were also significantly decreased in DEN + PB treated rats. When the treatment last only 2 weeks, the presence of PB did not change significantly the last parameters. In DEN + PB treated rats, the survival was prolonged and the tumor incidence decreased as compared with the results obtained by DEN alone. It is concluded that PB, which promotes carcinogenesis when administered after the DEN treatment, reduces the carcinogen effect when given simultaneously with DEN. This' anti - carcinogen' effect acts on the initiation as well as on the promotion of the precancerous lesions. Biochemical investigations are in progress to obtain more information about this' paradoxical' PB effect.

carcinogenic

carcinogenesis

hepatocarcinogenesis

preneoplastic foci

tumor

carcinogenesis

precancerous lesions

phenobarbital

diethylnitrosamine

phenobarbital

PB

diethylnitrosamine

DEN

DEN

DEN

PB

PB

DEN

DEN

DEN

PB

PB

DEN

PB

DEN

PB

DEN

DEN

PB

diethylnitrosamine

preneoplastic foci

diethylnitrosamine

precancerous lesions

diethylnitrosamine

preneoplastic foci

diethylnitrosamine

precancerous lesions

DEN

preneoplastic foci

DEN

precancerous lesions

DEN

preneoplastic foci

DEN

precancerous lesions

DEN

preneoplastic foci

DEN

precancerous lesions

DEN

preneoplastic foci

DEN

precancerous lesions

DEN

preneoplastic foci

DEN

precancerous lesions

DEN

preneoplastic foci

DEN

precancerous lesions

DEN

preneoplastic foci

DEN

precancerous lesions

DEN

preneoplastic foci

DEN

precancerous lesions

DEN

preneoplastic foci

DEN

precancerous lesions

DEN

preneoplastic foci

DEN

precancerous lesions


Input: Post - operative rigidity after fentanyl administration. A case of thoraco - abdominal rigidity leading to respiratory failure is described in the post - operative period in an elderly patient who received a moderate dose of fentanyl. This was successfully reversed by naloxone. The mechanisms possibly implicated in this accident are discussed.

rigidity

rigidity

respiratory failure

fentanyl

fentanyl

naloxone

fentanyl

rigidity

fentanyl

rigidity

fentanyl

rigidity

fentanyl

rigidity


Input: Postpartum psychosis induced by bromocriptine. Two multigravida patients with no prior psychiatric history were seen with postpartum psychosis, having received bromocriptine for inhibition of lactation. Bromocriptine given in high doses has been associated with psychosis in patients receiving the drug for Parkinson' s disease. These cases demonstrate that bromocriptine may cause psychosis even when given in low doses.

psychosis

psychiatric

psychosis

inhibition of lactation

psychosis

Parkinson' s disease

psychosis

bromocriptine

bromocriptine

Bromocriptine

bromocriptine

bromocriptine

psychosis

bromocriptine

psychosis

bromocriptine

psychosis

bromocriptine

psychosis

bromocriptine

psychosis

bromocriptine

psychosis

bromocriptine

psychosis

bromocriptine

psychosis

Bromocriptine

psychosis

Bromocriptine

psychosis

Bromocriptine

psychosis

Bromocriptine

psychosis

bromocriptine

psychosis

bromocriptine

psychosis

bromocriptine

psychosis

bromocriptine

psychosis


Input: A prospective study on the dose dependency of cardiotoxicity induced by mitomycin C. Since 1975 mitomycin C (MMC) has been suggested to be cardiotoxic, especially when combined with or given following doxorubicin. Data on dose dependency or incidence concerning this side effect were not known. We have initiated a prospective study to obtain some more data on these subjects. Forty - four MMC - treated patients were studied, 37 of them could be evaluated. All patients were studied by repeated physical examinations, chest X - rays, electro - and echocardiography and radionuclide left ventricular ejection fraction (EF) determinations. The results were evaluated per cumulative dose level. One of the patients developed cardiac failure after 30 mg m - 2 MMC and only 150 mg m - 2 doxorubicin. The cardiac failure was predicted by a drop in EF determined during a cold pressor test. None of the other patients developed clinical cardiotoxicity, nor did the studied parameters change. The literature on this subject was also reviewed. Based on the combined data from the present study and the literature, we suggest that MMC - related cardiotoxicity is dose dependent, occurring at cumulative dose levels of 30 mg m - 2 or more, mainly in patients also (previously or simultaneously) treated with doxorubicin. The incidence is likely to be less than 10% even for this risk group.

cardiotoxicity

cardiotoxic

cardiac failure

cardiac failure

cardiotoxicity

cardiotoxicity

mitomycin C

mitomycin C

MMC

doxorubicin

MMC

MMC

doxorubicin

MMC

doxorubicin

mitomycin C

cardiac failure

mitomycin C

cardiac failure

mitomycin C

cardiac failure

mitomycin C

cardiac failure

MMC

cardiac failure

MMC

cardiac failure

MMC

cardiac failure

MMC

cardiac failure

MMC

cardiac failure

MMC

cardiac failure

MMC

cardiac failure

MMC

cardiac failure

doxorubicin

cardiac failure

doxorubicin

cardiac failure

doxorubicin

cardiac failure

doxorubicin

cardiac failure

doxorubicin

cardiac failure

doxorubicin

cardiac failure


Input: Phlorizin - induced glycosuria does not prevent gentamicin nephrotoxicity in rats. Because rats with streptozotocin - induced diabetes mellitus (DM) have a high solute diuresis (glycosuria of 10 to 12 g / day), we have suggested that this may in part be responsible for their resistance to gentamicin - induced acute renal failure (ARF). The protection from gentamicin nephrotoxicity was studied in non - diabetic rats with chronic solute diuresis induced by blockage of tubular glucose reabsorption with phlorizin (P). DM rats with mild glycosuria (similar in degree to that of the P treated animals) were also studied. Unanesthetized adult female, Sprague - Dawley rats were divided in four groups and studied for 15 days. Group 1 (P alone) received P, 360 mg / day, for 15 days; Group II (P + gentamicin); Group III (gentamicin alone) and Group IV (mild DM + gentamicin). Nephrotoxic doses (40 mg / kg body wt / day) of gentamicin were injected during the last nine days of study to the animals of groups II to IV. In Group I, P induced a moderate and stable glycosuria (3. 9 + / - 0. 1 g / day, SE), and no functional or morphologic evidence of renal dysfunction (baseline CCr 2. 1 + / - 0. 1 ml / min, undetectable lysozymuria) or damage (tubular necrosis score [maximum 4], zero). In Group II, P did not prevent gentamicin - ARF (maximal decrease in CCr at day 9. 89%, P less than 0. 001; peak lysozymuria, 1863 + / - 321 micrograms / day; and tubular necrosis score, 3. 9 + / - 0. 1). These values were not different from those of Group III: maximal decrease in CCr 73% (P less than 0. 001); lysozymuria, 2147 + / - 701 micrograms / day; tubular necrosis score, 3. 8 + / - 0. 1. (ABSTRACT TRUNCATED AT 250 WORDS)

Phlorizin

gentamicin

streptozotocin

gentamicin

gentamicin

glucose

phlorizin

P

P

P

P

P

gentamicin

gentamicin

gentamicin

gentamicin

P

P

gentamicin

P

P

glycosuria

nephrotoxicity

diabetes mellitus

DM

glycosuria

acute renal failure

ARF

nephrotoxicity

diabetic

DM

glycosuria

DM

Nephrotoxic

glycosuria

renal dysfunction

tubular necrosis

ARF

tubular necrosis

tubular necrosis

streptozotocin

diabetes mellitus

streptozotocin

DM

streptozotocin

diabetic

streptozotocin

DM

streptozotocin

DM

gentamicin

acute renal failure

gentamicin

ARF

gentamicin

ARF

gentamicin

acute renal failure

gentamicin

ARF

gentamicin

ARF

gentamicin

acute renal failure

gentamicin

ARF

gentamicin

ARF

gentamicin

acute renal failure

gentamicin

ARF

gentamicin

ARF

gentamicin

acute renal failure

gentamicin

ARF

gentamicin

ARF

gentamicin

acute renal failure

gentamicin

ARF

gentamicin

ARF

gentamicin

acute renal failure

gentamicin

ARF

gentamicin

ARF

gentamicin

acute renal failure

gentamicin

ARF

gentamicin

ARF


Input: Tiapride in levodopa - induced involuntary movements. Tiapride, a substituted benzamide derivative closely related to metoclopramide, reduced levodopa - induced peak dose involuntary movements in 16 patients with idiopathic Parkinson' s disease. However, an unacceptable increase in disability from Parkinsonism with aggravation of end - of - dose akinesia led to its cessation in 14 patients. Tiapride had no effect on levodopa - induced early morning of " off - period " segmental dystonia. These results fail to support the notion that levodopa - induced dyskinesias are caused by overstimulation of a separate group of dopamine receptors.

Tiapride

levodopa

Tiapride

benzamide

metoclopramide

levodopa

Tiapride

levodopa

levodopa

dopamine

involuntary movements

involuntary movements

idiopathic Parkinson' s disease

Parkinsonism

akinesia

dystonia

dyskinesias

levodopa

involuntary movements

levodopa

involuntary movements

levodopa

akinesia

levodopa

dyskinesias

levodopa

involuntary movements

levodopa

involuntary movements

levodopa

akinesia

levodopa

dyskinesias

levodopa

involuntary movements

levodopa

involuntary movements

levodopa

akinesia

levodopa

dyskinesias

levodopa

involuntary movements

levodopa

involuntary movements

levodopa

akinesia

levodopa

dyskinesias


Input: Effects of the hippocampal deep brain stimulation on cortical epileptic discharges in penicillin - induced epilepsy model in rats. AIM: Experimental and clinical studies have revealed that hippocampal DBS can control epileptic activity, but the mechanism of action is obscure and optimal stimulation parameters are not clearly defined. The aim was to evaluate the effects of high frequency hippocampal stimulation on cortical epileptic activity in penicillin - induced epilepsy model. MATERIAL AND METHODS: Twenty - five Sprague - Dawley rats were implanted DBS electrodes. In group - 1 (n = 10) hippocampal DBS was off and in the group - 2 (n = 10) hippocampal DBS was on (185 Hz, 0. 5V, 1V, 2V, and 5V for 60 sec) following penicillin G injection intracortically. In the control group hippocampal DBS was on following 8 l saline injection intracortically. EEG recordings were obtained before and 15 minutes following penicillin - G injection, and at 10th minutes following each stimulus for analysis in terms of frequency, amplitude, and power spectrum. RESULTS: High frequency hippocampal DBS suppressed the acute penicillin - induced cortical epileptic activity independent from stimulus intensity. In the control group, hippocampal stimulation alone lead only to diffuse slowing of cerebral bioelectrical activity at 5V stimulation. CONCLUSION: Our results revealed that continuous high frequency stimulation of the hippocampus suppressed acute cortical epileptic activity effectively without causing secondary epileptic discharges. These results are important in terms of defining the optimal parameters of hippocampal DBS in patients with epilepsy.

epileptic

epilepsy

epileptic

epileptic

epilepsy

epileptic

epileptic

epileptic

epilepsy

penicillin

penicillin

penicillin G

penicillin - G

penicillin

penicillin G

epileptic

penicillin G

epilepsy

penicillin G

epileptic

penicillin G

epileptic

penicillin G

epilepsy

penicillin G

epileptic

penicillin G

epileptic

penicillin G

epileptic

penicillin G

epilepsy

penicillin - G

epileptic

penicillin - G

epilepsy

penicillin - G

epileptic

penicillin - G

epileptic

penicillin - G

epilepsy

penicillin - G

epileptic

penicillin - G

epileptic

penicillin - G

epileptic

penicillin - G

epilepsy


Input: Neural correlates of S - ketamine induced psychosis during overt continuous verbal fluency. The glutamatergic N - methyl - D - aspartate (NMDA) receptor has been implicated in the pathophysiology of schizophrenia. Administered to healthy volunteers, a subanesthetic dose of the non - competitive NMDA receptor antagonist ketamine leads to psychopathological symptoms similar to those observed in schizophrenia. In patients with schizophrenia, ketamine exacerbates the core symptoms of illness, supporting the hypothesis of a glutamatergic dysfunction. In a counterbalanced, placebo - controlled, double - blind study design, healthy subjects were administered a continuous subanesthetic S - ketamine infusion while differences in BOLD responses measured with fMRI were detected. During the scanning period, subjects performed continuous overt verbal fluency tasks (phonological, lexical and semantic). Ketamine - induced psychopathological symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS). Ketamine elicited psychosis like psychopathology. Post - hoc t - tests revealed significant differences between placebo and ketamine for the amounts of words generated during lexical and semantic verbal fluency, while the phonological domain remained unaffected. Ketamine led to enhanced cortical activations in supramarginal and frontal brain regions for phonological and lexical verbal fluency, but not for semantic verbal fluency. Ketamine induces activation changes in healthy subjects similar to those observed in patients with schizophrenia, particularly in frontal and temporal brain regions. Our results provide further support for the hypothesis of an NMDA receptor dysfunction in the pathophysiology of schizophrenia.

S - ketamine

N - methyl - D - aspartate

NMDA

NMDA

ketamine

ketamine

S - ketamine

Ketamine

Ketamine

ketamine

Ketamine

Ketamine

NMDA

psychosis

schizophrenia

schizophrenia

schizophrenia

glutamatergic dysfunction

psychosis

schizophrenia

schizophrenia

ketamine

psychosis

ketamine

psychosis

ketamine

psychosis

ketamine

psychosis

Ketamine

psychosis

Ketamine

psychosis

Ketamine

psychosis

Ketamine

psychosis

ketamine

psychosis

ketamine

psychosis

Ketamine

psychosis

Ketamine

psychosis

Ketamine

psychosis

Ketamine

psychosis


Input: Dopamine is not essential for the development of methamphetamine - induced neurotoxicity. It is widely believed that dopamine (DA) mediates methamphetamine (METH) - induced toxicity to brain dopaminergic neurons, because drugs that interfere with DA neurotransmission decrease toxicity, whereas drugs that increase DA neurotransmission enhance toxicity. However, temperature effects of drugs that have been used to manipulate brain DA neurotransmission confound interpretation of the data. Here we show that the recently reported ability of L - dihydroxyphenylalanine to reverse the protective effect of alpha - methyl - para - tyrosine on METH - induced DA neurotoxicity is also confounded by drug effects on body temperature. Further, we show that mice genetically engineered to be deficient in brain DA develop METH neurotoxicity, as long as the thermic effects of METH are preserved. In addition, we demonstrate that mice genetically engineered to have unilateral brain DA deficits develop METH - induced dopaminergic deficits that are of comparable magnitude on both sides of the brain. Taken together, these findings demonstrate that DA is not essential for the development of METH - induced dopaminergic neurotoxicity and suggest that mechanisms independent of DA warrant more intense investigation.

Dopamine

methamphetamine

dopamine

DA

methamphetamine

METH

DA

DA

DA

L - dihydroxyphenylalanine

alpha - methyl - para - tyrosine

METH

DA

DA

METH

METH

DA

METH

DA

METH

DA

neurotoxicity

toxicity

toxicity

toxicity

neurotoxicity

neurotoxicity

dopaminergic deficits

neurotoxicity

methamphetamine

neurotoxicity

methamphetamine

neurotoxicity

methamphetamine

neurotoxicity

methamphetamine

neurotoxicity

methamphetamine

neurotoxicity

methamphetamine

neurotoxicity

methamphetamine

neurotoxicity

methamphetamine

neurotoxicity

METH

neurotoxicity

METH

neurotoxicity

METH

neurotoxicity

METH

neurotoxicity

METH

neurotoxicity

METH

neurotoxicity

METH

neurotoxicity

METH

neurotoxicity

METH

neurotoxicity

METH

neurotoxicity

METH

neurotoxicity

METH

neurotoxicity

METH

neurotoxicity

METH

neurotoxicity

METH

neurotoxicity

METH

neurotoxicity

METH

neurotoxicity

METH

neurotoxicity

METH

neurotoxicity

METH

neurotoxicity

METH

neurotoxicity

METH

neurotoxicity

METH

neurotoxicity

METH

neurotoxicity


Input: Brainstem dysgenesis in an infant prenatally exposed to cocaine. Many authors described the effects on the fetus of maternal cocaine abuse during pregnancy. Vasoconstriction appears to be the common mechanism of action leading to a wide range of fetal anomalies. We report on an infant with multiple cranial - nerve involvement attributable to brainstem dysgenesis, born to a cocaine - addicted mother.

Brainstem dysgenesis

cocaine abuse

fetal anomalies

multiple cranial - nerve involvement

brainstem dysgenesis

cocaine - addicted

cocaine

cocaine

multiple cranial - nerve involvement


Input: The protective role of Nrf2 in streptozotocin - induced diabetic nephropathy. OBJECTIVE: Diabetic nephropathy is one of the major causes of renal failure, which is accompanied by the production of reactive oxygen species (ROS). Nrf2 is the primary transcription factor that controls the antioxidant response essential for maintaining cellular redox homeostasis. Here, we report our findings demonstrating a protective role of Nrf2 against diabetic nephropathy. RESEARCH DESIGN AND METHODS: We explore the protective role of Nrf2 against diabetic nephropathy using human kidney biopsy tissues from diabetic nephropathy patients, a streptozotocin - induced diabetic nephropathy model in Nrf2 (- / -) mice, and cultured human mesangial cells. RESULTS: The glomeruli of human diabetic nephropathy patients were under oxidative stress and had elevated Nrf2 levels. In the animal study, Nrf2 was demonstrated to be crucial in ameliorating streptozotocin - induced renal damage. This is evident by Nrf2 (- / -) mice having higher ROS production and suffering from greater oxidative DNA damage and renal injury compared with Nrf2 (+ / +) mice. Mechanistic studies in both in vivo and in vitro systems showed that the Nrf2 - mediated protection against diabetic nephropathy is, at least, partially through inhibition of transforming growth factor - beta1 (TGF - beta1) and reduction of extracellular matrix production. In human renal mesangial cells, high glucose induced ROS production and activated expression of Nrf2 and its downstream genes. Furthermore, activation or overexpression of Nrf2 inhibited the promoter activity of TGF - beta1 in a dose - dependent manner, whereas knockdown of Nrf2 by siRNA enhanced TGF - beta1 transcription and fibronectin production. CONCLUSIONS: This work clearly indicates a protective role of Nrf2 in diabetic nephropathy, suggesting that dietary or therapeutic activation of Nrf2 could be used as a strategy to prevent or slow down the progression of diabetic nephropathy.

streptozotocin

oxygen

streptozotocin

streptozotocin

glucose

diabetic nephropathy

Diabetic nephropathy

renal failure

diabetic nephropathy

diabetic nephropathy

diabetic nephropathy

diabetic nephropathy

diabetic nephropathy

renal damage

renal injury

diabetic nephropathy

diabetic nephropathy

diabetic nephropathy

streptozotocin

diabetic nephropathy

streptozotocin

Diabetic nephropathy

streptozotocin

diabetic nephropathy

streptozotocin

diabetic nephropathy

streptozotocin

diabetic nephropathy

streptozotocin

diabetic nephropathy

streptozotocin

diabetic nephropathy

streptozotocin

diabetic nephropathy

streptozotocin

diabetic nephropathy

streptozotocin

diabetic nephropathy

streptozotocin

diabetic nephropathy

streptozotocin

Diabetic nephropathy

streptozotocin

diabetic nephropathy

streptozotocin

diabetic nephropathy

streptozotocin

diabetic nephropathy

streptozotocin

diabetic nephropathy

streptozotocin

diabetic nephropathy

streptozotocin

diabetic nephropathy

streptozotocin

diabetic nephropathy

streptozotocin

diabetic nephropathy

streptozotocin

diabetic nephropathy

streptozotocin

Diabetic nephropathy

streptozotocin

diabetic nephropathy

streptozotocin

diabetic nephropathy

streptozotocin

diabetic nephropathy

streptozotocin

diabetic nephropathy

streptozotocin

diabetic nephropathy

streptozotocin

diabetic nephropathy

streptozotocin

diabetic nephropathy

streptozotocin

diabetic nephropathy


Input: High - dose tranexamic Acid is associated with nonischemic clinical seizures in cardiac surgical patients. BACKGROUND: In 2 separate centers, we observed a notable increase in the incidence of postoperative convulsive seizures from 1. 3% to 3. 8% in patients having undergone major cardiac surgical procedures. These events were temporally coincident with the initial use of high - dose tranexamic acid (TXA) therapy after withdrawal of aprotinin from general clinical usage. The purpose of this review was to perform a retrospective analysis to examine whether there was a relation between TXA usage and seizures after cardiac surgery. METHODS: An in - depth chart review was undertaken in all 24 patients who developed perioperative seizures. Electroencephalographic activity was recorded in 11 of these patients, and all patients had a formal neurological evaluation and brain imaging studies. RESULTS: Twenty - one of the 24 patients did not have evidence of new cerebral ischemic injury, but seizures were likely due to ischemic brain injury in 3 patients. All patients with seizures did not have permanent neurological abnormalities. All 24 patients with seizures received high doses of TXA intraoperatively ranging from 61 to 259 mg / kg, had a mean age of 69. 9 years, and 21 of 24 had undergone open chamber rather than coronary bypass procedures. All but one patient were managed using cardiopulmonary bypass. No evidence of brain ischemic, metabolic, or hyperthermia - induced causes for their seizures was apparent. CONCLUSION: Our results suggest that use of high - dose TXA in older patients in conjunction with cardiopulmonary bypass and open - chamber cardiac surgery is associated with clinical seizures in susceptible patients.

tranexamic Acid

tranexamic acid

TXA

TXA

TXA

TXA

seizures

convulsive

seizures

seizures

seizures

cerebral ischemic injury

seizures

ischemic brain injury

seizures

neurological abnormalities

seizures

brain ischemic

hyperthermia

seizures

seizures

tranexamic Acid

seizures

tranexamic Acid

convulsive

tranexamic Acid

seizures

tranexamic Acid

seizures

tranexamic Acid

seizures

tranexamic Acid

seizures

tranexamic Acid

seizures

tranexamic Acid

seizures

tranexamic Acid

seizures

tranexamic Acid

seizures

tranexamic acid

seizures

tranexamic acid

convulsive

tranexamic acid

seizures

tranexamic acid

seizures

tranexamic acid

seizures

tranexamic acid

seizures

tranexamic acid

seizures

tranexamic acid

seizures

tranexamic acid

seizures

tranexamic acid

seizures

TXA

seizures

TXA

convulsive

TXA

seizures

TXA

seizures

TXA

seizures

TXA

seizures

TXA

seizures

TXA

seizures

TXA

seizures

TXA

seizures

TXA

seizures

TXA

convulsive

TXA

seizures

TXA

seizures

TXA

seizures

TXA

seizures

TXA

seizures

TXA

seizures

TXA

seizures

TXA

seizures

TXA

seizures

TXA

convulsive

TXA

seizures

TXA

seizures

TXA

seizures

TXA

seizures

TXA

seizures

TXA

seizures

TXA

seizures

TXA

seizures

TXA

seizures

TXA

convulsive

TXA

seizures

TXA

seizures

TXA

seizures

TXA

seizures

TXA

seizures

TXA

seizures

TXA

seizures

TXA

seizures


Input: Recurrent dysosmia induced by pyrazinamide. Pyrazinamide can have adverse effects such as hepatic toxicity, hyperuricemia or digestive disorders. In rare cases, alterations in taste and smell function have been reported for pyrazinamide when combined with other drugs. We report a case of reversible olfactory disorder related to pyrazinamide in a woman, with a positive rechallenge. The patient presented every day a sensation of smelling something burning 15 min after drug intake. Dysosmia disappeared completely after pyrazinamide withdrawal and recurred after its rechallenge. The case was reported to the Tunisian Centre of Pharmacovigilance.

dysosmia

hepatic toxicity

hyperuricemia

olfactory disorder

Dysosmia

pyrazinamide

Pyrazinamide

pyrazinamide

pyrazinamide

pyrazinamide

pyrazinamide

dysosmia

pyrazinamide

olfactory disorder

pyrazinamide

Dysosmia

Pyrazinamide

dysosmia

Pyrazinamide

olfactory disorder

Pyrazinamide

Dysosmia

pyrazinamide

dysosmia

pyrazinamide

olfactory disorder

pyrazinamide

Dysosmia

pyrazinamide

dysosmia

pyrazinamide

olfactory disorder

pyrazinamide

Dysosmia

pyrazinamide

dysosmia

pyrazinamide

olfactory disorder

pyrazinamide

Dysosmia


Input: Longitudinal assessment of air conduction audiograms in a phase III clinical trial of difluoromethylornithine and sulindac for prevention of sporadic colorectal adenomas. A phase III clinical trial assessed the recurrence of adenomatous polyps after treatment for 36 months with difluoromethylornithine (DFMO) plus sulindac or matched placebos. Temporary hearing loss is a known toxicity of treatment with DFMO, thus a comprehensive approach was developed to analyze serial air conduction audiograms. The generalized estimating equation method estimated the mean difference between treatment arms with regard to change in air conduction pure tone thresholds while accounting for within - subject correlation due to repeated measurements at frequencies. Based on 290 subjects, there was an average difference of 0. 50 dB between subjects treated with DFMO plus sulindac compared with those treated with placebo (95% confidence interval, - 0. 64 to 1. 63 dB; P = 0. 39), adjusted for baseline values, age, and frequencies. In the normal speech range of 500 to 3, 000 Hz, an estimated difference of 0. 99 dB (- 0. 17 to 2. 14 dB; P = 0. 09) was detected. Dose intensity did not add information to models. There were 14 of 151 (9. 3%) in the DFMO plus sulindac group and 4 of 139 (2. 9%) in the placebo group who experienced at least 15 dB hearing reduction from baseline in 2 or more consecutive frequencies across the entire range tested (P = 0. 02). Follow - up air conduction done at least 6 months after end of treatment showed an adjusted mean difference in hearing thresholds of 1. 08 dB (- 0. 81 to 2. 96 dB; P = 0. 26) between treatment arms. There was no significant difference in the proportion of subjects in the DFMO plus sulindac group who experienced clinically significant hearing loss compared with the placebo group. The estimated attributable risk of ototoxicity from exposure to the drug is 8. 4% (95% confidence interval, - 2. 0% to 18. 8%; P = 0. 12). There is a < 2 dB difference in mean threshold for patients treated with DFMO plus sulindac compared with those treated with placebo.

difluoromethylornithine

sulindac

difluoromethylornithine

DFMO

sulindac

DFMO

DFMO

sulindac

DFMO

sulindac

DFMO

sulindac

DFMO

sulindac

colorectal adenomas

adenomatous polyps

hearing loss

toxicity

hearing loss

ototoxicity

sulindac

hearing loss

sulindac

hearing loss

sulindac

hearing loss

sulindac

hearing loss

sulindac

hearing loss

sulindac

hearing loss

sulindac

hearing loss

sulindac

hearing loss

sulindac

hearing loss

sulindac

hearing loss

sulindac

hearing loss

sulindac

hearing loss


Input: Increased mental slowing associated with the APOE epsilon4 allele after trihexyphenidyl oral anticholinergic challenge in healthy elderly. OBJECTIVES: The objectives of this study were to examine the relationship between APOE epsilon4 and subjective effects of trihexyphenidyl on measures reflecting sedation and confusion and to investigate the relationship between trihexyphenidyl - induced subjective effects and objective memory performance. METHODS: This study comprised 24 cognitively intact, health elderly adults (12 APOE epsilon4 carriers) at an outpatient geriatric psychiatry research clinic. This was a randomized, double blind, placebo - controlled, three - way, crossover experimental design. All participants received 1. 0 mg or 2. 0 mg trihexyphenidyl or placebo administered in counterbalanced sequences over a period of three consecutive weeks. Bond and Lader' s visual analog scales and alternate versions of the Buschke Selective Reminding Test were administered in a repeated measures design at baseline, 1, 2. 5, and 5 hours postdrug administration. RESULTS: A 2. 0 - mg oral dose of trihexyphenidyl resulted in increased subjective ratings of mental slowness in carriers of the APOE epsilon4 allele only. Drug effects as determined by difference scores between 2. 0 mg trihexyphenidyl and placebo on ratings of mental slowness significantly correlated with total and delayed recall on the Buschke Selective Reminding Test in carriers of the APOE epsilon4 allele only. However, no significant effects were found with other visual analog scales reflecting subjective sedation and clear - headedness. CONCLUSION: The epsilon4 allele in healthy elderly was associated with increased subjective mental slowing after trihexyphenidyl anticholinergic challenge.

mental slowing

confusion

mental slowness

mental slowness

mental slowing

trihexyphenidyl

trihexyphenidyl

trihexyphenidyl

trihexyphenidyl

trihexyphenidyl

trihexyphenidyl

trihexyphenidyl

trihexyphenidyl

mental slowing

trihexyphenidyl

mental slowness

trihexyphenidyl

mental slowness

trihexyphenidyl

mental slowing

trihexyphenidyl

mental slowing

trihexyphenidyl

mental slowness

trihexyphenidyl

mental slowness

trihexyphenidyl

mental slowing

trihexyphenidyl

mental slowing

trihexyphenidyl

mental slowness

trihexyphenidyl

mental slowness

trihexyphenidyl

mental slowing

trihexyphenidyl

mental slowing

trihexyphenidyl

mental slowness

trihexyphenidyl

mental slowness

trihexyphenidyl

mental slowing

trihexyphenidyl

mental slowing

trihexyphenidyl

mental slowness

trihexyphenidyl

mental slowness

trihexyphenidyl

mental slowing

trihexyphenidyl

mental slowing

trihexyphenidyl

mental slowness

trihexyphenidyl

mental slowness

trihexyphenidyl

mental slowing

trihexyphenidyl

mental slowing

trihexyphenidyl

mental slowness

trihexyphenidyl

mental slowness

trihexyphenidyl

mental slowing


Input: Behavioral effects of pubertal anabolic androgenic steroid exposure in male rats with low serotonin. The goal of this study was to assess the interactive effects of chronic anabolic androgenic steroid (AAS) exposure and brain serotonin (5 - hydroxytryptamine, 5 - HT) depletion on behavior of pubertal male rats. Serotonin was depleted beginning on postnatal day 26 with parachlorophenylalanine (PCPA 100 mg / kg, every other day); controls received saline. At puberty (P40), half the PCPA - treated rats and half the saline - treated rats began treatment with testosterone (T, 5 mg / kg, 5 days / week). Behavioral measures included locomotion, irritability, copulation, partner preference, and aggression. Animals were tested for aggression in their home cage, both with and without physical provocation (mild tail pinch). Brain levels of 5 - HT and its metabolite, 5 - hydroxyindoleacetic acid (5 - HIAA), were determined using HPLC. PCPA significantly and substantially depleted 5 - HT and 5 - HIAA in all brain regions examined. Chronic T treatment significantly decreased 5 - HT and 5 - HIAA in certain brain areas, but to a much lesser extent than PCPA. Chronic exposure to PCPA alone significantly decreased locomotor activity and increased irritability but had no effect on sexual behavior, partner preference, or aggression. T alone had no effect on locomotion, irritability, or sexual behavior but increased partner preference and aggression. The most striking effect of combining T + PCPA was a significant increase in attack frequency as well as a significant decrease in the latency to attack, particularly following physical provocation. Based on these data, it can be speculated that pubertal AAS users with low central 5 - HT may be especially prone to exhibit aggressive behavior.

steroid

serotonin

steroid

serotonin

5 - hydroxytryptamine

5 - HT

Serotonin

parachlorophenylalanine

PCPA

PCPA

testosterone

T

5 - HT

5 - hydroxyindoleacetic acid

5 - HIAA

PCPA

5 - HT

5 - HIAA

T

5 - HT

5 - HIAA

PCPA

PCPA

T

T

PCPA

5 - HT

irritability

aggression

aggression

irritability

aggression

irritability

aggression

aggressive behavior

testosterone

irritability

testosterone

aggression

testosterone

aggression

testosterone

irritability

testosterone

aggression

testosterone

irritability

testosterone

aggression

testosterone

aggressive behavior

T

irritability

T

aggression

T

aggression

T

irritability

T

aggression

T

irritability

T

aggression

T

aggressive behavior

T

irritability

T

aggression

T

aggression

T

irritability

T

aggression

T

irritability

T

aggression

T

aggressive behavior

T

irritability

T

aggression

T

aggression

T

irritability

T

aggression

T

irritability

T

aggression

T

aggressive behavior

T

irritability

T

aggression

T

aggression

T

irritability

T

aggression

T

irritability

T

aggression

T

aggressive behavior