Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The differential effects of beta-adrenoceptor subtypes on potassium fluxes and exercise capacity were compared in eight healthy young men using single oral doses of the selective beta 2-adrenoceptor antagonist ICI-118551, the selective beta 1-adrenoceptor antagonist atenolol or the non-selective beta-adrenoceptor antagonist propranolol. The study was randomized, double-blind and placebo controlled. 2. Potassium in the venous effluent from the exercising muscles increased progressively with increasing exercise intensity. This response was augmented by propranolol, whereas neither atenolol nor ICI-118551 modified the response. After exercise potassium concentration fell exponentially with no difference between the treatment regimens. 3. Cumulative work was significantly reduced by ICI-118551 (6.4%, P = 0.04) and by propranolol (12.4%, P less than 0.01), whereas the reduction with atenolol (5.6%) did not reach statistical significance. 4. Atenolol and propranolol reduced peak heart rate by 23% and 29%, and peak systolic blood pressure by 9% and 11% respectively during maximal exercise. ICI-118551 caused a non-significant reduction in heart rate during submaximal exercise, with a significant reduction at maximum exercise (6% reduction), whereas systolic blood pressure was not different from placebo. Diastolic blood pressures were similar across all treatment regimens. 5. Similar glucose concentrations were obtained at baseline and at exhaustion during all treatment regimens. Lactate concentrations were comparable for any given exercise intensity irrespective of treatment regimens. Propranolol reduced lactate concentrations from the exercising muscles at maximum exercise in proportion to the reduction of maximal exercise capacity. 6. The subjective perception of fatigue was not affected by either beta 1- or beta 2-adrenoceptor blockade.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of selective beta 2-adrenoceptor blockade on serum potassium and exercise performance in normal men. 168 47

1. Xamoterol (Corwin, Carwin, Corwil, Xamtol, ICI 118,587), a beta 1-adrenoceptor partial agonist, improves both systolic and diastolic function in heart failure patients. 2. Double-blind, randomised studies comparing xamoterol with placebo showed that the beneficial haemodynamic effects of xamoterol produced significant improvements in exercise capacity and symptoms in patients with mild to moderate heart failure. These studies formed the basis for a large European multicentre study programme which recruited over 1000 patients, randomised to xamoterol (200 mg twice daily, n = 617), digoxin (0.125 mg twice daily, n = 135) or placebo (n = 300) for 3 months. 3. Efficacy was assessed by measuring exercise capacity and symptoms. The xamoterol group improved exercise capacity by 37% compared with an 18% improvement in the placebo group. Differences in the symptom scores measured by visual analogue scales and Likert scores indicated significant improvements by xamoterol in the cardinal symptoms of heart failure, dyspnoea and fatigue. 4. Analyses of data from subsets of patients in the study showed that elderly patients, patients on no other heart failure therapy and patients with cardiomegaly all had similar improvements in exercise and symptoms to those seen in the whole study population. In the subset which included digoxin treatment, xamoterol produced significantly greater improvements in exercise capacity than digoxin (33% vs 17%, P less than 0.05) and was associated with fewer side-effects. 5. Xamoterol is therefore a promising addition to heart failure therapies currently available.
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PMID:Xamoterol, a beta 1-adrenoceptor partial agonist: review of the clinical efficacy in heart failure. 257 51

The quianazoline antifolate N10-propargyl-5,8-dideazafolic acid (ICI 155,387), an inhibitor of thymidylate synthetase (TS), was evaluated for clinical toxicity in a phase I trial. The compound was given once every week as a bolus injection. Fourteen patients with advanced cancer were treated at doses of 10-30 mg/m3. Four patients from the lowest to the highest dose developed severe renal toxicity, detected by a reversible decrease in the Cr-EDTA clearance. Hepatotoxicity was observed with transient elevations of alanine aminotransferase (ALT) in 10 patients and alkaline phosphatase in nine patients. Neither the incidence nor the severity of these toxicities was dose related. Two patients developed feelings of fatigue, which in one patient coincided with a decrease in Cr-EDTA clearance. No myelotoxicity, dermatological, gastrointestinal toxicity or mucositis was seen. No tumour responses due to ICI 155,387 occurred. The severity and the erratic nature of the renal side-effects suggest that this schedule cannot be recommended for further development of this compound in Phase II trials.
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PMID:A phase I evaluation of N10-propargyl-5,8-dideazafolic acid. 335 7

Experimental data in animals and humans have demonstrated connections between right and left motor cortices. Interactions between these cortical areas can be explored with electrical or magnetic stimulation. In the present study we examined the interhemispheric effect of fatigue on intracortical facilitation (ICF) and inhibition (ICI) using a paired-pulse transcranial magnetic stimulation (TMS) paradigm. Ten healthy subjects performed pinch grips with their left hand with 50% maximum voluntary contraction (MVC) until fatigue occurred. In the control experiment, the same number of pinch grips was performed with 5% MVC without inducing fatigue. Motor evoked potentials (MEP) produced by single and paired pulse TMS over the left motor cortex were recorded from right first dorsal interosseous muscle (FDI) and right abductor digiti minimi muscle (ADM) before and after the tasks. ICF of the right FDI was significantly reduced after fatigue ( P=0.0008). Fifteen minutes after finishing the task ICF had returned to baseline values. There was no change of ICF of right FDI in the control experiment without inducing fatigue. In both experiments the right ADM did not show significant MEP changes. Additional control experiments showed that M-responses and F-waves were unchanged in right FDI after performing the fatigue task with left FDI, and TMS test pulse amplitudes were significantly reduced in left FDI after fatigue. Fatigue caused by pinch grips induces a short-lasting and task-specific suppression of intracortical facilitation in the motor cortex of an homologous contralateral hand muscle. These results indicate interhemispheric interactions between the two motor cortices that are still effective after cessation of movements.
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PMID:Fatigue suppresses ipsilateral intracortical facilitation. 1235 75