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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although fatigue is a well-known phenomenon and the phrase "exercised until exhaustion" is commonly understood, there is no unequivocal agreement on the fundamental nature of the fatigue process. Ammonia was linked to the development of fatigue as early as 1922, when ammonia production was observed from stimulated nerve and the question whether there could be a relationship between ammonia production and the muscle activity was raised. The immediate source of ammonia from muscle appears to be a result of the deamination of AMP and is more apparent in fast-twitch than in slow-twitch fibers. More recently, increases in blood ammonia levels have been reported in rats after swimming and in humans after arm work, maximal cycle ergometry, and treadmill exercise. Elevated blood ammonia has also been linked to a surprising variety of functional and metabolic neurological disturbances other than exercise and fatigue, including the development of hepatic coma, convulsions from ammonia toxicity precipitated by high-pressure oxygen breathing, epileptic seizures, and decreased neuronal excitability. In addition, a number of genetic disorders (inborn errors in metabolism, or IEMs) are characterized by elevated blood ammonia concentrations. Symptoms of neural disability in all of the above conditions have been related to the concentration of ammonia in blood. Although these studies do not relate to exercise or fatigue directly, it is conceivable that our understanding of the effect of high concentrations of blood ammonia in these clinical conditions may provide valuable insight into the effect of ammonia during exercise. This paper reviews the effect of ammonia production during exercise and other conditions upon purposeful activity and the development of fatigued states.
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PMID:Ammonia metabolism in exercise and fatigue: a review. 634 52

In a comparative randomized double-blind study, 73 patients underwent myelography using iopamidol (36 patients) or metrizamide (37 patients) as contrast medium. The overall diagnostic adequacy of iopamidol myelography was found to be comparable to that of metrizamide myelography. The incidence of examinations graded as superior (64%) or adequate (36%) with iopamidol was equivalent to that with metrizamide (57% superior, 43% adequate). Adverse reactions after iopamidol myelography were fewer, less severe, and generally of shorter duration than those associated with metrizamide. In the iopamidol group, adverse reactions occurred in nine (25%) patients, all of whom experienced mild or moderate headache, one with nausea, vomiting, and fatigue. In the metrizamide group, adverse reactions occurred in 17 (46%) patients, all of whom experienced mild or moderate headache, six with nausea and vomiting and four with back and leg pain. Of nine individuals who underwent myelography using 300 mg 1/ml metrizamide injected via lateral C1-C2 puncture, three experienced a toxic encephalopathy with confusion, dysphasia, headache, nausea, and vomiting, and a fourth individual suffered severe nausea, vomiting, fever, and irregular pulse. Encephalopathy was not observed in any of the 11 patients in whom myelography was performed via lateral C1-C2 puncture with a similar concentration of iopamidol. No seizures were encountered, and no clinically significant changes in laboratory studies were observed with either contrast medium.
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PMID:Iopamidol and metrizamide for myelography: prospective double-blind clinical trial. 638 81

We carried out an open study of the effects of large doses (12 to 16 gm per day) of oral choline on medically intractable human complex partial seizures (CPS). Marked increases of plasma choline concentration (75 to 300%) in three subjects were associated with (1) shorter duration of CPS, (2) less postseizure fatigue, and (3) slight increase of seizure frequency. Both the patients and their families considered the patients much improved. No differences in any of these evaluations were noted in a fourth subject who had less of an increase (21%) of plasma choline content. The results suggest that oral choline therapy may be a useful adjunct in the treatment of intractable CPS. A blinded prospective study will be necessary to assess this possibility.
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PMID:Effects of oral choline on human complex partial seizures. 677 20

The purpose of this study was establishing the effect of moderate exercise on EEG tracings in young epileptics. The model of graded exercise was 15-minute work on a cycle ergometer. The effect of the exercise on the pattern of simultaneously recorded EEG was compared with the effect of 3-minute hyperventilation. After testing a control group of 20 young subjects without evidence of organic brain damage or with this damage causing no epilepsy another group of 43 epileptics was studied. In none of these patients the intensity of changes in EEG increased during the exercise but evident EEG differences could be detected during different stages of the exercise in 28 patients with significant generalized discharges. It was found that during the exercise in nearly all patients the number of discharges decreased while during hyperventilation it increased. In 10 patients in this group a repeated rise in the number of discharges was observed immediately after the exercise which was connected usually with greater fatigue after the exercise. In the light of these results the authors conclude that moderate exercise inhibits rather seizure activity in EEG contrary to hyperventilation which increases these changes.
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PMID:[Effect of physical exertion on seizure discharges in the EEG of epilepsy patients]. 680 81

Temporal and site correlation of local cerebral blood flow (1-CBF), tissue redox state, energy metabolism, tissue pH, and cerebral electrophysiological activity in induced cerebral ischemia was performed in rats in an effort to obtain helpful clues for the management of occlusive cerebrovascular disease. CBF decreased acutely in both the embolized and nonembolized hemispheres but returned toward normal in 5 minutes. However, total cerebral oxidative metabolism remained depressed throughout the 30-minute observation period despite improved perfusion. The change in CBF correlated with the development and resolution of tissue acidosis, which was maximal 3 minutes after embolization but became alkaline after 30 minutes, possibly due to accumulation of sodium lactate. Oxidized form of nicotinamide-adenine dinucleotide and cytochrome a,a3 quickly became reduced in the ischemic core, but a tardyspontaneous postischemic tissue perfusion resulted in their hyperoxidation. The CBF-metabolism uncoupling as well as postischemic hyperoxidation of the electron transport system, which is associated with accumulation of pyruvate and lactate, probably resulted from stagnation of electron flow at the entrance to the mitochondrial respiratory processes. Seizures could not account for these results, as paroxysmal changes in the EEG usually appeared only in the nonembolized hemisphere and were not dependent upon lack of energy. These studies confirm that metabolic failure may persist in ischemic tissue despite adequate reperfusion, which may, in fact, contribute to tissue damage through hyperoxidation.
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PMID:The dissociation of cerebral blood flow, metabolism, and function in the early stages of developing cerebral infarction. 743 71

The objectives of exercise testing in congestive heart failure (CHF) may be summarized as follows: (a) detect impaired cardiac performance, (b) grade severity of cardiac failure and classify functional capability, and (c) assess effects of interventions. Several different methods are available to make these assessments, and we have to ask ourselves how well exercise testing achieves these objectives. It has to be kept in mind that the power generated by the exercising muscles is dependent on the oxygen delivery to the skeletal muscles. Oxygen uptake is the result of an integrated performance of the lungs, heart, and peripheral circulation. In patients, as well as in normal subjects, oxygen uptake is related to hemodynamic indices such as cardiac output, stroke volume, or exercise duration when a stepwise regulated maximal exercise protocol is used. However, there are major differences in the concept of a true maximum in normal subjects versus heart failure patients. Fit-normal subjects will achieve a real maximal oxygen uptake, whereas patients may stop testing before a maximum is reached because of symptoms such as dyspnea or leg fatigue. Therefore, it is better if the actual oxygen uptake can be measured. "Peak" rather than true maximal oxygen uptake has been suggested for the classification of the severity of heart failure. Peripheral factors modify the cardiac output through such factors as vascular resistance, organ function, and hormonal release. Maximal exercise will stress the cardiovascular system to a point where the weakest chain will impose a limiting effect.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The role of exercise testing in heart failure. 751 35

Since their initial description in 1957, the interferons (IFNs) have been increasingly used to treat a wide array of diseases. Acute adverse effects, i.e. 'flu-like' syndromes, hypo- or hypertension, tachycardia, headache, myalgias and gastrointestinal disorders, occur within the first hour or day after starting treatment. They are seldom treatment-limiting and are easily manageable. Sub-acute and chronic effects develop after several days, usually within 2 and 4 weeks of therapy. The most typical is neurological toxicity, including fatigue/asthenia, and behavioural and cognitive changes. Such symptoms may seriously impair quality of life and result in treatment discontinuation. Seizures have seldom been described. Other infrequent central nervous system adverse effects include vertigo, cramp and oculomotor nerve paralysis. Distal paraesthesias and peripheral neuropathy have been reported. IFN-associated autoimmunity is quite rare but a matter of concern. Biological or clinical manifestations usually require several months to become apparent. Autoantibodies have been shown to develop in most patients but have been inconsistently associated with clinical symptoms of systemic lupus erythematosus, rheumatoid-like arthritis and thyroiditis. Both hypo- and hyperthyroidism have been described but are usually reversible. Other infrequent autoimmune reactions include diabetes, pemphigus and worsening of multiple sclerosis. Although several patients present with a pre-existing autoimmune disorder, no predisposing factor has been clearly established. While hypotension and tachycardia are the most frequent acute cardiovascular complications, a few additional cases of cardiac arrhythmias and myocardial ischaemia have been reported after a short course or several weeks of treatment. These latter complications do not appear to be dose-dependent or age-related. Isolated cases of congestive heart failure have also been described. Mild proteinuria has been observed in 15 to 25% of patients, but acute renal toxicity is uncommon. A transient rise in serum aminotransferase levels is frequently noted during the first stage of therapy, especially in patients receiving the highest dosages. Direct hepatotoxicity is extremely rare. Autoimmune hepatitis, which is ill-diagnosed as chronic viral hepatitis, and de novo induction of autoimmune hepatitis, account for the majority of liver diseases. Haematotoxicity is relatively common but mild to moderate, and develops gradually during the first weeks of treatment. Neutropenia is the most common haematological toxicity, but is usually not dose-limiting and resolves rapidly upon drug discontinuation. Myelosuppression, autoimmune and immune allergic haemolytic anaemias and thrombocytopenias have seldom been described. Cutaneous adverse effects comprised nonspecific erythema and hair loss and, less frequently, vasculitis, local ulcerations at the site of injection and exacerbation of psoriasis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical toxicity of the interferons. 751 63

A 44-year-old man with a documented 12-year history of progressive sensorineural hearing loss developed a generalized tonic-clonic seizure followed by a visual field deficit and apraxia. Six months later he developed a peripheral neuropathy and muscle fatigue followed by a slowly progressive aphasia and cortical blindness as well as increased seizure activity. A computed tomography scan showed bilateral basal ganglion calcification. The serum lactate level was elevated at 3.4 mEq/dL. A muscle biopsy enabled the diagnosis of mitochondrial myopathy. This disorder is presented as an unusual cause of progressive sensorineural hearing loss in adults.
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PMID:Mitochondrial encephalomyopathy: a rare genetic cause of sensorineural hearing loss. 757 56

Tiagabine is a new antiepileptic drug which acts by a novel mechanism, inhibiting the reuptake of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) into neurons and glia. A double-blind, placebo-controlled, crossover trial was undertaken, based upon a response-dependent design. Ninety-four patients with complex partial seizures with or without secondary generalised tonic-clonic seizures were recruited into an open screening phase and tiagabine was added to their existing drug therapy in doses titrated to reduce seizure frequency by > or = 25% or to the limit of tolerance. Forty-six responders were subsequently randomised to a double-blind crossover trial in which tiagabine was compared with placebo. Forty-two patients completed the trial. A significant reduction in the frequency of complex partial and secondary generalised tonic clonic seizures was seen. Twenty-six percent had a reduction of > or = 50% in the frequency of their complex partial seizures, and of the 27 patients who also had secondary generalised tonic clonic seizures, 63% experienced a reduction of > or = 50%. No interactions with baseline antiepileptic drugs were detected and no serious adverse reactions occurred. The commonest adverse events were tiredness, dizziness and headache. We conclude that tiagabine has promising antiepileptic effects. Further trials are underway.
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PMID:Adjunctive treatment of partial seizures with tiagabine: a placebo-controlled trial. 764 74

Gabapentin is an antiepileptic drug with an unknown mechanism of action apparently dissimilar to that of other antiepileptic agents, and possessing some desirable pharmacokinetic traits. The drug is not protein bound, is not metabolised and does not induce liver enzymes, diminishing the likelihood of drug interactions with other antiepileptic agents and drugs such as oral contraceptives. Although gabapentin is a structural analogue of the neurotransmitter gamma-aminobutyric acid (GABA), which does not cross the blood-brain barrier, gabapentin penetrates into the CNS and its activity is seemingly distinct from GABA-related effects. Present clinical evaluation is largely restricted to proof of efficacy trials of gabapentin as add-on therapy in patients with partial epilepsy resistant to conventional treatment. Gabapentin (usually 600 to 1800 mg/day) provides notable benefit, reducing seizure frequency by > or = 50% in 18 to 28% of patients with refractory partial seizures, as shown in 3 double-blind, placebo-controlled trials. Overall, seizure frequency decreased by 18 to 32% during 3-month treatment periods. Patients with complex partial seizures, and partial seizures secondarily generalised, are particularly likely to respond to gabapentin. Current experience with the drug in other seizure types, and as monotherapy, is limited. Mild adverse events, commonly somnolence, fatigue, ataxia and dizziness, have been reported in about 75% of gabapentin recipients. While the drug has been well tolerated when administered to a few patients for periods of up to 5 years, its long term tolerability profile has yet to be fully expounded. Thus, with its favourable pharmacokinetic profile, and efficacy in some refractory patients, gabapentin is poised to fill a niche as an adjunct to the treatment of partial epilepsy. Promising results obtained thus far warrant further work to clarify its long term tolerability, its possible efficacy in other seizure types, its position relative to other agents and its use as monotherapy. In the meantime, gabapentin is likely to provide a much-needed option in a therapeutic area requiring complex management.
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PMID:Gabapentin. A review of its pharmacological properties and clinical potential in epilepsy. 769 32


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