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)

Labrador Retriever myopathy (LRM) has become a relatively common muscular disease. The objective of our prospective study was to determine by segregation analyses a plausible mode of inheritance within a Labrador Retriever population. Therefore we performed neurological examinations, as well as electromyographic and histopathological evaluations of 58 closely related dogs. Seven dogs with an average age of 27.8 months had clinical signs consistent with LRM including exercise intolerance or fatigue. The diagnosis was based on neurological deficits and confirmed by histopathological results of muscle biopsy. We found in all cases obvious differences in fiber calibre size associated with texture disturbances. In addition, we found 41 clinically normal dogs with histological findings consistent with LRM. Three genetic models, the major gene, the mixed inheritance as well as the environmental model, were evaluated by segregation analyses. They were applied to an extended pedigree including 164 non-randomly ascertained related Labradors. According to phenotype the clinically examined dogs were divided into two different data sets. One data set distinguished between clinically normal and abnormal dogs, the second data set between histopathologically normal and abnormal dogs. We concluded that the clinical form of LRM is transmitted by a major gene and controlled by an autosomal recessive mode of inheritance. Furthermore, for expression of the subclinical form an additional gene or an environmental factor is responsible. Our findings suggest that LRM is similar to limb-girdle muscular dystrophy in man and therefore, may be used in the future as an animal model.
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PMID:Genetic aspects of Labrador Retriever myopathy. 1244 79

The type 1 ryanodine receptor (RyR1) on the sarcoplasmic reticulum (SR) is the major calcium (Ca2+) release channel required for skeletal muscle excitation-contraction (EC) coupling. RyR1 function is modulated by proteins that bind to its large cytoplasmic scaffold domain, including the FK506 binding protein (FKBP12) and PKA. PKA is activated during sympathetic nervous system (SNS) stimulation. We show that PKA phosphorylation of RyR1 at Ser2843 activates the channel by releasing FKBP12. When FKB12 is bound to RyR1, it inhibits the channel by stabilizing its closed state. RyR1 in skeletal muscle from animals with heart failure (HF), a chronic hyperadrenergic state, were PKA hyperphosphorylated, depleted of FKBP12, and exhibited increased activity, suggesting that the channels are "leaky." RyR1 PKA hyperphosphorylation correlated with impaired SR Ca2+ release and early fatigue in HF skeletal muscle. These findings identify a novel mechanism that regulates RyR1 function via PKA phosphorylation in response to SNS stimulation. PKA hyperphosphorylation of RyR1 may contribute to impaired skeletal muscle function in HF, suggesting that a generalized EC coupling myopathy may play a role in HF.
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PMID:PKA phosphorylation activates the calcium release channel (ryanodine receptor) in skeletal muscle: defective regulation in heart failure. 1262 52

Relationship among thyroid dysfunction and musculoskeletal symptoms has been known for years. Autoimmunic thyroiditis is the most common cause of hypothyrosis. A patient who suffered from myopathy secondary to autoimmunic thyroiditis and hypothyrosis is described in this article. Attention has been drawn to proximal muscle weakness and general fatigue which is common in such cases. Significant elevation of muscle enzymes is typical. Usually no specific signs can be found on muscle biopsy. Much efforts should be put to distinguish myopathy secondary to hypothyrosis from polymyalgia rheumatica, polymyositis or myopathies caused by other diseases. Similar data of literature are reviewed in the article.
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PMID:[A rare case of differential diagnosis of myopathy]. 1279 74

The safety of the hydroxymethyl glutaryl-coenzyme A reductase inhibitors (statins) has been called into question following the recent withdrawal from the market of one of the class, cerivastatin. The withdrawal of cerivastatin highlighted concerns regarding the safety of the entire class. According to data from several large clinical trials, the statins (except cerivastatin) are well tolerated. The most important and clinically relevant adverse effect reported with statins is myopathy. Myopathy is a clinical diagnosis of elevated creatine phosphokinase and/or myalgia along with fatigue. However, the severe from (i.e. statin-associated rhabdomyolysis) is an uncommon syndrome and occurs at a rate of approximately 1/100,000 patients/years. Statin-associated myopathy is related to statin doses, and often to drug/drug interactions. Other clinically relevant adverse effects associated with statin therapy include liver transminases elevation, which is relatively mild and often self-limiting There is no evidence from clinical trials of a significant alteration of ophthalmological function with statins. The issue of statin-induced cancer remains inconclusive. Overall, the statins seem to exhibit a favourable risk/benefit ratio, and this undoubtedly justifies life-long clinical use of statins for cardiovascular prevention.
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PMID:[Adverse effects of statins]. 1282 4

Muscular fatigue may result from HIV infection, and may be associated with antiretroviral drug treatment. Clinical features linked to muscle biopsy findings may assist in determining etiology, and guide treatment decisions. This case series examined HIV patients in an ambulatory HIV clinic who received antiretroviral therapy, and complained of unexplained muscular fatigue. Clinical features with measurement of acid-base status, levels of lactate, aminotransferases, triglycerides and creatine kinase were correlated to light and electron microscopic results of muscle biopsy. Three patients with acquired mitochondrial changes on biopsy shared common features of lactatemia, elevated aminotransferases and triglycerides, and ultrasonographic hepatic steatosis. A fourth patient with normal mitochondria had myositis with fibrosis, but no systemic symptoms. Biochemical parameters were unremarkable, except for a high creatine kinase. Acquired mitochondrial disease may manifest as systemic illness and muscular fatigue. Unique metabolic changes and other organ dysfunction may precede overt physical signs of HIV myopathy.
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PMID:Clinical correlates to muscle biopsy findings in HIV patients experiencing fatigue: a case series. 1294 81

Although colchicine induced myopathy has been described in patients with chronic renal failure, colchicine induced myopathy with myotonia has been reported very rarely. A 49-year-old man with chronic renal failure was hospitalised for investigation of fatigue, malaise and severe pain in all extremities. He was on colchicine therapy for 5 months. Neurological examination showed mildly decreased sensation in a distal symmetric pattern in lower extremities, moderate proximal limb weakness, hyporeflexia and severe myalgia on palpation. No clinical evidence of myotonia was present. Laboratory studies showed elevated creatine phosphokinase (CK), lactic dehydrogenase (LDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. Electromyographic (EMG) findings were compatible with myopathy and abundant, widespread myotonic discharges were determined. Muscle biopsy was consistent with vacuolar myopathy. After withdrawal of colchicine, CK, LDH, AST and ALT levels were normalised and the symptoms were disappeared gradually. In conclusion, the detection of myopathic motor unit potentials with myotonic discharges on EMG in patients on colchicine therapy is an important finding and it is possible to suggest that this clue may lead to the invasive procedure of muscle biopsy unnecessary.
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PMID:Colchicine-induced myopathy with myotonia in a patient with chronic renal failure. 1295 45

In this study, the authors describe 2 patients who experienced confirmed exposures to anticholinesterases that commenced in the 1970s. Subsequently, elevations in creatine phosphate kinase (CPK) were initially detected more than a decade following the first acute exposure. Beginning in the early 1980s, the patients suffered from progressive generalized muscle weakness, chronic fatigue, myopathy, neuropathy, and severe neurobehavioral impairments. Previous occupational exposures included pyridostigmine, as well as isopropyl methylphosphonofluoridate (percutaneous lethal dose [LD50] < 28 mg/kg body weight), and 1 patient had exposure to agricultural organophosphates. The authors hypothesize that the workers' CPK elevations, first detected more than a decade following acute exposures to anticholinesterases, were sentinel events for impending muscle damage and necrosis. Many Gulf War veterans with Gulf War disease who reported exposures to anticholinesterases 1 decade earlier currently suffer from vague neuromuscular and cognitive impairments. Therefore, medical programs for Gulf War veterans with Gulf War Syndrome should include surveillance for elevated CPK, abnormalities of neuromuscular conduction, and genetic susceptibility, and they should promote therapeutic trials for palliation.
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PMID:Creatine phosphate kinase elevations signaling muscle damage following exposures to anticholinesterases: 2 sentinel patients. 1536 80

Heart failure (HF) is a syndrome resulting from the inability of the cardiac pump to meet the energy requirements of the body. Despite intensive work, the pathogenesis of the cardiac intracellular abnormalities that result from HF remains incompletely understood. Factors that lead to abnormal contraction and relaxation in the failing heart include metabolic pathway abnormalities that result in decreased energy production, energy transfer and energy utilization. Heart failure also affects the periphery. Patients suffering from heart failure always complain of early muscular fatigue and exercise intolerance. This is linked in part to intrinsic alterations of skeletal muscle, among which decreases in the mitochondrial ATP production and in the transfer of energy through the phosphotransfer kinases play an important role. Alterations in energy metabolism that affect both cardiac and skeletal muscles argue for a generalized metabolic myopathy in heart failure. Recent evidence shows that decreased expression of mitochondrial transcription factors and mitochondrial proteins are involved in mechanisms causing the energy starvation in heart failure. This review will focus on energy metabolism alterations in long-term chronic heart failure with only a few references to compensated hypertrophy when necessary. It will briefly describe the energy metabolism of normal heart and skeletal muscles and their alterations in chronic heart failure. It is beyond the scope of this review to address the metabolic switches occurring in compensated hypertrophy; readers could refer to well-documented reviews on this subject.
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PMID:Energy metabolism in heart failure. 1466 Jul 9

We reported a patient with so-called "dropped head plus syndrome", a non-progressive myopathy characterized by striking neck extensor weakness followed by progressive limb weakness which is well controlled by azathioprine. This 74-year-old man complained of neck and shoulder fatigue followed by progressive neck extensor weakness over 7 months. On physical examination, neck extensor strength was 4/5 on the MMT scale, but the remainder of the neurological examination and blood tests were normal. Needle EMG showed myopathic changes in the right trapezius and biceps brachialis muscles. Without any treatment, he developed weakness of upper and lower limb muscles about 8 months later, and Gowers' sign was positive. Blood test and needle EMG was unchanged. Muscle biopsy of the left trapezius, deltoid and supraspinatus muscles disclosed nonspecific myopathic changes consisting of variation in fiber size with disorganized intermyofibrillar networks in all the fibers, and there were rimmed vacuoles in some fibers of the deltoid muscle. There was no change on corticosteroids, but there was a dramatic improvement with azathioprine and his muscle symptoms disappeared. We, therefore, made the diagnosis of "dropped head plus syndrome". This appears to be the first such case in Japan.
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PMID:[Dropped head plus syndrome; a case report]. 1472 63

Macrophagic myofasciitis is a recently identified inflammatory myopathy mostly described in adult French patients complaining of arthro-myalgias and fatigue. It is probably due to intramuscular injection of aluminium-containing vaccines and is characterized by a typical muscular infiltrate of large macrophages with aluminium inclusions. We report a 1-year-old Italian child presenting irritability, delayed motor development, hyperCKemia (up to 10 times the normal value), and typical features of macrophagic myofasciitis on muscle biopsy. The child recovered fully after steroid therapy. Macrophagic myofasciitis is a new treatable cause of motor retardation and hyperCKemia in children, and is probably more common than reported. Diagnosis requires a high index of suspicion and can be missed if biopsy is performed outside the vaccination site.
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PMID:Macrophagic myofasciitis: an infantile Italian case. 1473 66


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