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)

Simvastatin belongs to a class of lipid-lowering drugs which completely inhibit 3-hydroxy-3-methylglutaryl co-enzyme A (HMG CoA) reductase. The commonest adverse effects of therapy with simvastatin HMG CoA reductase inhibitors are gastro-intestinal disturbance, myositis and myopathy. Rhabdomyolysis leading to renal failure has been reported, but it appears to be very rare, except in patients also receiving cyclosporin, nicotinic acid or gemfibrozil. Here we report the case of an elderly lady who was known to have chronic renal failure, but who developed rhabdomyolysis following simvastatin therapy. Her symptoms of muscle pain, fatigue, myoglobulinuria, oliguria and pulmonary oedema appeared 48 h after the first dose of simvastatin. Simvastatin was immediately stopped, and the patient was dialysed for 1 week. Her renal function improved and came back. We suggest that extreme care should be exercised in prescribing this drug, particularly for the elderly with renal impairment.
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PMID:Simvastatin-induced rhabdomyolysis in a patient with chronic renal failure. 1127 41

Diaphragmatic strength, which can be roughly estimated by non invasive techniques such as maximal inspiratory pressure or sniff nasal pressure, is specifically assessed by the measurement of transdiaphragmatic pressure during electric or magnetic phrenic nerve stimulation. However, muscle endurance is probably a more relevant parameter in pulmonary disease. Recent progress in the field of diaphragm biology were mainly obtained in animal models. Data in human disease are currently restricted to COPD and steroid induced myopathy. In COPD patients, recent studies demonstrated significant adaptations of diaphragm fibers susceptible to counterbalance the mechanical disadvantage due to hyperinflation. These changes include an increased proportion of fatigue resistant type I fibers, a decrease in sarcomere length and an increase in mitochondrial density. Regarding corticosteroid induced myopathy, numerous experimental studies are available whereas data are scarce in human disease. Respiratory corticosteroid myopathy is characterized by markedly decreased strength and endurance of inspiratory muscles. Histologic data obtained by quadriceps biopsies in COPD patients demonstrated diffuse fiber atrophy, increased variation in diameter of fibers and diffuse necrotic fibers. Recent data in rats suggest that decreased IGF expression induced by corticosteroids might contribute to diaphragmatic changes.
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PMID:[Clinical investigation of diaphragmatic function. Relationships with the biology of muscle]. 1093 20

We have recently shown that mitochondrial function and energy metabolism are altered in the myocardium as well as in slow and fast locomotor muscles of rats subjected to prolonged congestive heart failure (CHF) suggesting a generalized metabolic myopathy in heart failure. Here, we investigate whether the diaphragm of CHF animals, which experiences both increased work and the general systemic influence of heart failure, will also be susceptible to altered energy metabolism. Biopsies were obtained from the costal diaphragm of failing rats 8 months after aortic banding. A marked increase in type I and type IIa myosin heavy chains at the expense of types IIx and IIb, suggests an adaptation towards a slower phenotype. Glycolytic enzymes decreased in CHF diaphragm with an increase in the H:M lactate dehydrogenase isoenzyme ratio. These results suggest a reorientation of the diaphragm muscle towards a slow, fatigue-resistant phenotype. However, maximal oxidative capacity assessed in saponin-permeabilized fibers in the presence of ADP was considerably reduced in CHF diaphragm (7.7+/-0.4 v 11.8+/-0.7 micromol O2/min/g dry weight in sham P<0.001), suggesting an alteration in oxidative phosphorylation. Furthermore, ADP sensitivity of CHF mitochondria was significantly increased (apparent Km for ADP 308+/-21 v 945+/-106 microM in sham P<0.001), whereas sensitivity to ADP in the presence of creatine was comparable (Km 79+/-12 v 90+/-11 microM in sham). In heart failure, therefore, the diaphragm muscle seems to adapt towards a more slow and economical contraction as a result of increased workload, but this adaptation is limited by the disease-induced altered mitochondrial function.
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PMID:Dual influence of disease and increased load on diaphragm muscle in heart failure. 1127 23

Patients treated with nucleoside analogue reverse transcriptase inhibitors (NRTIs) develop a varying degree of myopathy or neuropathy after long-term therapy. Zidovudine (AZT) causes myopathy; zalcitabine (ddC), didanosine (ddl) and lamuvidine (3TC) cause neuropathy; stavudine (d4T) and fialuridine (FIAU) cause neuropathy or myopathy and lactic acidosis. The tissue distribution of phosphorylases responsible for phosphorylation of NRTIs relates to their selective tissue toxicity. The myopathy is characterized by muscle wasting, myalgia, fatigue, weakness and elevation of CK. The neuropathy is painful, sensory and axonal. In vitro, NRTIs inhibit the gamma-DNA polymerase, responsible for replication of mtDNA, and cause mtDNA dysfunction. In vivo, patients treated with AZT, the best studied NRTI, develop a mitochondrial myopathy with mtDNA depletion, deficiency of COX (complex IV), intracellular fat accumulation, high lactate production and marked phosphocreatine depletion, as determined with in vivo MRS spectroscopy, due to impaired oxidative phosphorylation. Animals or cultured cells treated with NRTIs develop neuropathy, myopathy, or cell destruction with similar changes in the mitochondria. There is evidence that the NRTI-related neuropathy is also due to mitochondrial toxicity. The NRTIs (AZT, ddC, ddl, d4T, 3TC) contain azido groups that compete with natural thymidine triphosphate as substrates of DNA pol-gamma and terminate mtDNA synthesis. In contrast, FIAU that contains 3'-OH groups serves as an alternate substrate for thymidine triphosphate with DNA pol-gamma and is incorporated into the DNA causing permanent mtDNA dysfunction. The NRTI-induced mitochondrial dysfunction has an influence on the clinical application of these agents, especially at high doses and when combined. They have produced in humans a new category of acquired mitochondrial toxins that cause clinical manifestations resembling the genetic mitochondrial disorders.
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PMID:Peripheral neuropathy and antiretroviral drugs. 1129 2

Fluoroquinolones cause myalgia, but this complication is not clearly documented. We describe a patient who developed myalgia and rhabdomyolysis during fluoroquinolone treatment. The patient was a 33-year-old man treated with norfloxacin for common cystitis. He complained of general muscular fatigue, tendon disorders, and articular pain during treatment. When the antimicrobial agent was stopped, symptoms decreased, with persistence of slight myalgia for 10 days. Rhabdomyolysis was detected. Six months later, investigation by 31P magnetic resonance spectroscopy revealed an oxidative disorder and an abnormal abundance of phosphomonoesters. In vitro contracture tests led to a diagnosis of malignant hyperthermia susceptibility. Our case shows that for any subject presenting myalgia with rhabdomyolysis triggered by fluoroquinolone treatment, the presence of a latent myopathy should be investigated.
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PMID:Malignant hyperthermia susceptibility revealed by myalgia and rhabdomyolysis during fluoroquinolone treatment. 1140 39

There has been a debate for many years on whether muscular training is beneficial or harmful for patients with myopathic disorders and the role of exercise training in the management of these patients is still controversial. Much of this confusion is because of the lack of well-designed controlled training studies on this heterogenic group of disorders. Because effective therapies are still lacking, the patients have to rely on symptomatic treatment in which continuous physiotherapy plays an important role. There is thus still a need for studies evaluating the short- and long-term effects of muscular training in different types of myopathic disorders. We need to elucidate whether muscular training can increase strength and resistance to fatigue, but most importantly, we need to clarify whether training can improve specific functional abilities of the patient with myopathy. Future studies should give us specific information on what type of training, endurance or strength training, is to be preferred for different myopathies. The effect of strength training in one type of muscle disorder is not directly applicable to another, but is largely dependent on the underlying biological defect. From the studies published so far, high-resistance strength training at submaximal and possibly also at near-maximal levels seem beneficial, at least in the short perspective for slowly progressive myopathic disorders. However, the long-term effects of such training have not been systematically studied. In rapidly progressive myopathies, which are caused by deficient structural proteins such as in Duchenne's muscular dystrophy, the use of high-resistance training is far more controversial and questionable. If exercise regimens are to be used, they should preferably commence in the early stages of the disease, at which time there is still a substantial amount of trainable muscle fibres.
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PMID:Muscle training in muscular dystrophies. 1141 49

A great deal of controversy and speculation surrounds the etiology of Chronic Fatigue Syndrome (CFS) in human patients and the existence of a similar illness in animals. To evaluate the association with a presumptive staphylococcal infection and bacteremia, seven dogs and eight cats diagnosed with CFS (two meeting the CDC working case definition) were submitted to rapid blood cultures and fresh blood smears investigations. Nine out of 15 blood cultures proved Staph-positive and four isolates were specified as S. xilosus (3) and S. intermedius (1). The presence of micrococci-like organisms in the blood was of common observation among these subjects, in association with fatigue/pain-related symptoms and biochemical abnormalities suggestive of a myopathy. Following treatment with a low dosage arsenical drug (thiacetarsamide sodium, Caparsolate, i.v., 0.1 ml/kg/day) all patients experienced complete remission. Micrococci disappeared from the blood at post-treatment controls made 10-30 days later. The outcomes were compared with those of five healthy controls and five 'sick with other illness' patients showing significant difference.
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PMID:Chronic Fatigue Syndrome (CFS) in 15 dogs and cats with specific biochemical and microbiological anomalies. 1144 Jan 90

Renal replacement treatment options are life-saving treatments for patients with end-stage renal disease (ESRD). However, prolonged survival in patients with ESRD is associated with various functional and morphological disorders from almost all systems. Anaemia, deconditioning, cardiac dysfunction. impairment of cardiac autonomic control and skeletal muscle weakness and fatigue, primarily because of 'uraemic' myopathy and neuropathy, are the main predisposing factors for their poor functional ability. Physical training is being recommended as a complementary therapeutic modality. There are generally 3 methods of exercise training applied in patients with ESRD: (i) the supervised outpatient programme that is held in a rehabilitation centre; (ii) a home exercise rehabilitation programme; and (iii) exercise rehabilitation programme during the first hours of the haemodialysis treatment in the renal unit. All the available training data show that the application of an exercise training programme in patients with ESRD enhances their physical fitness. This improvement is due to central and mainly peripheral adaptations. Exercise training in these patients increases aerobic capacity, causes favourable left ventricular functional adaptations, reduces blood pressure in patients with hypertension, modifies other coronary risk factors, increases the cardiac vagal activity and suppresses the incidence of cardiac arrhythmias. Moreover, exercise training has beneficial effects on muscle structural and functional abnormalities. These central and peripheral adaptations to exercise training cause an increase in their functional capacity and offer them achance of a better quality of life. Moreover, exercise training improves exercisee tolerance of renal post-transplant patients.
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PMID:Central and peripheral adaptations to physical training in patients with end-stage renal disease. 1150 21

Carnitine is a conditionally essential metabolite that plays a critical role in cell physiology by participating in transesterification reactions and preventing organic acid accumulation. A number of disease states are characterized by carnitine depletion that may lead to metabolic and clinical disturbances. In maintenance hemodialysis, carnitine is lost through dialytic membranes, leading in selected patients to carnitine depletion with a relative increase of the esterified forms. Carnitine supplementation after or during dialysis counteracts such alterations and may be associated with some clinical benefits. Recent meta-analyses of the literature indicate that carnitine supplementation in hemodialysis patients may improve the hematological status (allowing a reduction of the requirement for erythropoietin), the exercise tolerance, the plasma lipid profile, and the intradialytic symptoms. In addition, carnitine supplementation may improve cardiac functions, protein metabolism, and insulin resistance. Carnitine supplementation has been recently approved by the US Food and Drug Administration not only for the treatment, but also for the prevention of carnitine depletion in dialysis patients. Furthermore, clinical guidelines developed by both American and European nephrological societies suggest that a trial with carnitine supplementation could be recommended in selected dialysis patients who do not adequately respond to standard therapy for certain conditions, such as severe and persistent muscle cramps or hypotension during dialysis, lack of energy affecting quality of life, skeletal muscle weakness or myopathy, cardiomyopathy, and anemia of uremia unresponsive to or requiring large doses of erythropoietin.
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PMID:Carnitine metabolism in uremia. 1157 25

Chronic heart failure is one of the most serious medical problems in the United States, affecting some 4 million persons. In spite of its common occurrence, and comprehensive literature regarding this condition, no unifying hypothesis has been accepted to explain the signs and symptoms of chronic heart failure. The cardiocirculatory and neurohormonal models place an emphasis on left ventricular ejection fraction and cardiac output and do not provide appropriate explanations for the symptoms of breathlessness and fatigue. The muscle hypothesis supplements these conventional models. It proposes that abnormal skeletal muscle in heart failure results in activation of muscle ergoreceptors, leading to an increase in ventilation and sensation of breathlessness, the perception of fatigue, and sympathetic activation. At least one fourth of patients with chronic heart failure are limited by skeletal muscle abnormalities rather than cardiac output. Cardiac rehabilitation exercise can lead to an increase in exercise capacity that is superior to that gained from digitalis or angiotensin-converting enzyme inhibitors. Exercise tends to reverse the skeletal muscle myopathy of chronic heart failure and reduces the abnormal ergoreflex. Other interventions that have been shown to have a favorable outcome include localized muscle group training, respiratory muscle training, and dietary approaches. The possibility that osteopathic manipulative treatment might be of benefit is an attractive, but untested, possibility.
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PMID:The muscle hypothesis: a model of chronic heart failure appropriate for osteopathic medicine. 1168 Nov 64


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