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)

Amyloid deposition in skeletal muscle is a well-recognized but rare occurrence. Sixteen such cases seen in a 17-year period (1979 to 1996) out of a total of 3,937 muscle biopsy specimens (0.004%) form this study group. Either Congo red or sulfated alcian blue stains were routinely performed in each biopsy to screen for amyloid. Patients in this study (eight men, eight women) ranged in age from 42 to 90 years (mean, 61 years) at initial presentation. The most common symptoms at presentation included weakness/fatigue (n = 10), autonomic symptoms (n = 8), and weight loss/decreased appetite (n = 7). Five patients had a concomitant malignancy (myeloma, n = 3; malignant carcinoid tumor, n = 1; melanoma, n = 1). Two patients had known hereditary forms of amyloidosis. Five patients had amyloid diagnosed on another organ biopsy (excluding peripheral nerve). Histologically, amyloid was deposited in the interstitium or perivascular region in 14 muscles and endomysial region in seven muscles. All cases were confirmed with Congo red staining (apple green birefringence) or by electron microscopic identification of fibrillary amyloid material. Scattered angular atrophic esterase-positive muscle myofibers indicative of acute denervation atrophy were seen in 14 muscles. Eight muscles showed small group atrophy, and seven showed myofiber type grouping. Scattered regenerating muscle fibers were seen in nine cases, degenerating myofibers in six, and foci of chronic endomysial and perivascular inflammation in two. Four muscles showed type II muscle fiber atrophy. A concomitant sural nerve biopsy specimen was evaluated in seven patients; all seven contained amyloid, confirmed either by Congo red staining or electron microscopic examination. In two nerves, there was a mild loss of myelinated axons; four had a moderate loss, and one, severe loss. Six of seven nerves showed predominantly axonopathic changes. In conclusion, (1) the prevalence rate of amyloid myopathy in muscle biopsy specimens was low (in this series, 0.004%); (2) only a minority of patients had multiple myeloma, and most presented with muscle weakness/fatigue or autonomic symptoms; (3) most of the muscles showed neurogenic features histologically; (4) all concomitant sural nerve biopsy specimens contained amyloid, and most showed a predominance of axonopathic changes.
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PMID:Amyloid myopathy: clinicopathologic study of 16 cases. 959 69

A 46-year-old white female was admitted for decompensated cor pulmonale (CP). It had not interfered with her daily activities and she had not experienced shortness of breath, fatigue or muscle weakness prior to the onset of right heart failure. A thorough investigation revealed severe generalized muscle weakness with restrictive chest bellows disease and secondary CP (mean pressure in the pulmonary artery 60 mm Hg). After having refused respiratory support the patient died a few days after admission. The muscle biopsy was consistent with adult-onset acid-maltase deficiency. This is a rare case of metabolic myopathy presenting as decompensated CP without previous symptoms of muscle weakness. This condition can easily be treated with nocturnal ventilatory support, improving the quality and length of life.
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PMID:Decompensated cor pulmonaleas the first manifestation of adult-onset myopathy. 973 Aug 2

Lovastatin, an inhibitor of the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (the major regulatory enzyme of the mevalonate pathway of cholesterol synthesis), displays antitumor activity in experimental models. We therefore conducted a Phase I trial to characterize the tolerability of lovastatin administered at progressively higher doses to cancer patients. From January 1992 to July 1994, 88 patients with solid tumors (median age, 57 +/- 14 years) were treated p.o. with 7-day courses of lovastatin given monthly at doses ranging from 2 to 45 mg/kg/day. The inhibitory effects of lovastatin were monitored through serum concentrations of cholesterol and ubiquinone, two end products of the mevalonate pathway. Concentrations of lovastatin and its active metabolites were also determined, by bioassay, in the serum of selected patients. Cyclical treatment with lovastatin markedly inhibited the mevalonate pathway, evidenced by reductions in both cholesterol and ubiquinone concentrations, by up to 43 and 49% of pretreatment values, respectively. The effect was transient, however, and its magnitude appeared to be dose independent. Drug concentrations reached up to 3.9 micrometer and were in the range associated with antiproliferative activity in vitro. Myopathy was the dose-limiting toxicity. Other toxicities included nausea, diarrhea, and fatigue. Treatment with ubiquinone was associated with reversal of lovastatin-induced myopathy, and its prophylactic administration prevented the development of this toxicity in a cohort of 56 patients. One minor response was documented in a patient with recurrent high-grade glioma. Lovastatin given p.o. at a dose of 25 mg/kg daily for 7 consecutive days is well tolerated. The occurrence of myopathy, the dose-limiting toxicity, can be prevented by ubiquinone supplementation. To improve on the transient inhibitory activity of this dosing regimen on the mevalonate pathway, alternative schedules based on uninterrupted administration of lovastatin should also be studied.
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PMID:Phase I study of lovastatin, an inhibitor of the mevalonate pathway, in patients with cancer. 981 94

Zidovudine is known to be responsible for a mitochondrial myopathy with ragged-red fibres and mitochondrial DNA depletion in muscle. Lactic acidosis alone or associated with hepatic abnormalities has also been reported. A single report mentioned the concomitant occurrence of muscular and hepatic disturbances and lactic acidosis in a patient receiving zidovudine, but muscle and liver tissues were not studied. A 57-year-old man with AIDS, who had been treated with zidovudine for 3 years, developed fatigue and weight loss. Serum creatine kinase and hepatic enzyme levels were high. Lactic acidosis was present. Liver biopsy showed diffuse macrovacuolar and microvacuolar steatosis. After withdrawal of zidovudine, creatine kinase, aspartate aminotransferase, and alanine aminotransferase levels normalised within 5 days, and lactacidaemia decreased. Acidosis persisted. The patient became confused and febrile and died 8 days after detection of high blood lactic acid. A muscle sample obtained at autopsy showed mitochondrial abnormalities with ragged-red fibres and lipid droplet accumulation. Southern blot analysis showed depletion of mitochondrial DNA, affecting skeletal muscle and liver tissue. No depletion was found in myocardium and kidney. This case emphasises that zidovudine treatment can induce mitochondrial multisystem disease, as revealed in our case by myopathy, liver steatosis and lactic acidosis.
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PMID:Zidovudine-induced mitochondrial disorder with massive liver steatosis, myopathy, lactic acidosis, and mitochondrial DNA depletion. 1070 83

Myasthenia gravis is a disorder characterized by weakness and fatigue of voluntary muscles. The muscular disorder is generalized in 85% and confined to extraocular muscles in 15% of patients. The disease is graded based on pattern and severity of muscular involvement. Myasthenia gravis is an autoimmune disease which leads to a reduction of the number of acetylcholine receptors (Ach-R) at the muscular motor endplate. This results in less receptors available for stimulation, lower amplitude stimulations, less muscle fiber activation, and the resultant clinical findings of weakness in the affected muscles. The work-up and treatment of this disease originated from an understanding of its pathogenesis. Diagnostic tests include use of anticholinesterase agents (tensilon test), curare test, repetitive nerve stimulation, Ach-R antibody assay, and single fiber electromyography. Medical therapy includes use of anticholinesterase agents, immunotherapy, and plasmapheresis.
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PMID:Myasthenia gravis: clinical features, pathogenesis, evaluation, and medical management. 993 Jul 11

Scleromyxedema is a disorder characterized by a typical rash due to the accumulation of mucin in the dermis. It is always associated with a monoclonal protein in the serum and can have a wide variety of systemic manifestations. We describe a 40-year-old woman who had scleromyxedema associated with a monoclonal G lambda protein. Severe systemic symptoms included fatigue, esophageal dysmotility, and myopathy. Symptoms resolved completely with oral prednisone therapy, and she remained in clinical remission 24 months after use of prednisone was discontinued. Scleromyxedema is commonly treated with alkylating agents, which have been associated with pronounced morbidity and mortality. We suggest that oral corticosteroid therapy may be a reasonable initial choice for treating this disease and that alkylating agents be reserved for corticosteroid-refractory disease.
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PMID:Scleromyxedema: a complete response to prednisone. 1031 80

Morbidity and mortality derived from asthma continue to be a main public health problem in many countries, in spite of the advances in the knowledge on the disease and its treatment. There are several risk factors for asthma attack which have to be considered in the management of patients in order to prevent exacerbations and mortality. Smooth bronchial muscle constriction and inflammation with oedema of the bronchial wall are the facts that cause airway flow and resistance disturbances, with hyperinflation, leading to a bigger respiratory work. On the other hand, the bronchial obstruction leads to a ventilation-perfusion disequilibrium and hypoxia. At the beginning of the process there is hypocarbia, but when the attack progresses muscle fatigue happens, and retention of CO2, being a sing of alarm (predictive of respiratory failure) a normal and rising PaCO2. The evaluation of an acute asthmatic patient should accomplish a clinical and objective assessment (peak flow rate and saturation of O2), in order to classify the crisis in: mild, moderate or severe. Managing acute asthmatic patient includes: oxygen, bronchodilator ss2 agonists at high and even continuous doses and systemic corticosteroids to prevent the progression and to control inflammation. These procedures should be promptly instituted. Although there is less evidence on their beneficial effects other measures as intravenous aminophylline, nebulized anticholynergics, magnesium sulphate and intravenous ss2 agonists may be used when the conventional therapy is not quickly successful and the patient is in a critical situation, at a real risk of respiratory failure, and in order to avoid mechanical ventilation. If this is finally instituted, controlled hypoventilation with permissive hypercarbia is now recommended, to avoid barotrauma, which used to be a frequent complication when more aggressive attitude was the rule. Interaction between paralytic agents and corticosteroids may produce a miopathy, so the recommendation now is to try not to use paralytic agents, even with profound sedation of needed. Sixty four patients were treated on 77 occasions in the Pediatric Intensive Care Unit of our hospital. They were 0,5 to 13,9 years old, being 50% less than 5 years old. It was the first attack in 9 (14%) patients. The standard management consisted of oxygen, frequently or continuously nebulized salbutamol and intravenous methylprednisolone (1 to 6 mg/kg/day). Furthermore nebulized ipratropium bromide was administered 58 times (75%), as well as intravenous aminophylline 69 (89%), intravenous salbutamol 23 (30%), magnesium sulphate 16 (21%) and ketamine 10 (13%). Antibiotics were given 22 times (29%). Two 15 month old infants received mechanical ventilation in three occasions, and relevant complications happened (pneumothorax and myopathy, and pneumomediastinum and bronchiolitis obliterans respectively). Fifty six patients have been followed for a period of 3 to 110 months (median 48 months), and 16 (29%) have needed high doses (equal to or move than 800 mcg of budesonide or equivalent). There are data on lung function in 36 of them, FEV1 is normal (> 85% of predicted, between 86 and 127) in 26 (78%) and < 85% (65 to 84%) of predicted in 8 (22%) FEV1 rises more than 15% (16 to 23%) in four patients after the inhalation of a ss2 agonist. Inhaled anesthetic agents and heliox have been used in some pediatric cases. After a severe asthma attack the strategy of management should be reviewed, as well as the possible risk factors.
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PMID:[Round Table: Severe asthma in pediatrics: treatment of acute crises]. 1035 7

The influence of dexamethasone on diaphragm function, its oxidative capacity, fiber cross-sectional areas, the content of glycogen and ultrastructural changes were determined in Wistar rats by receiving dexamethasone (2 mg/kg) muscle injection for two weeks. We noted dexamethasone treatment leads to significant atrophy of the mass of diaphragm, reduction of fiber cross-sectional areas (CSA) of type II a, II b fibers. Under high frequency (100 Hz) stimulation, the tention of the diaphragm muscle strips was decreased and diaphragm fatigue resistance (1/2 RT) was significantly improved. Histochemically, ATPase activity in type I and type II b fibers of the diaphragm was significantly reduced and a significant reduction of succinate dehydrogenase activity in the diaphragm was also observed, but increased glycogen was seen in the diaphragm. Ultrastructural changes including mitochondrial hyperplasia, swelling, myofibillae focus destructure were evident. It is concluded that steroid-induced myopathy may also involve the diaphragm.
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PMID:[Experimental studies about effect of dexamethasone on diaphragm of normal rats]. 1037 96

In this paper we describe 3 clinical cases of hypothyroidism causing myopathy and hyperammonemia. The patients, all females, aged 32 to 64 years, presented with hoarseness, fatigue, dyspepsia (case I), difficulty speaking secondary to the sensation of tongue swelling and hoarseness (case II), and progressive weight gain and difficulty speaking secondary to tongue swelling after delivery (case III). Laboratory tests showed a marked increase in creatine phosphokinase (up to 4090 U/L; normal values 24-176 U/L) of muscle origin, and an increase in transaminases and ammonia (124 to 150 micrograms/dL; normal values up to 75 micrograms/dL). Hypothyroidism was confirmed by TSH > 100 microIU/mL (normal values 0.3-5 microIU/mL). Treatment only with L-thyroxine determined the complete and persistent recovery of well-being and of biochemical abnormalities. The patients remained in good health after more than 2 years of follow-up. Our finding of hyperammonemia caused by the lack of thyroid hormones in 3 patients with hypothyroid myopathy appears to be of a certain interest as, to our knowledge, this phenomenon has not been previously described. In conclusion our hypothesis is that increased muscle production of ammonia secondary to the hypothyroid myopathy determined an increased ammonia load, resulting in hyperammonemia. Decreased liver ureagenesis induced by the lack of thyroid hormones also contributed to the hyperammonemia.
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PMID:[Hyperammonemia during hypothyroidism: an unusual biohumoral finding normalized by hormonal replacement treatment]. 1063 22

Muscle involvement in hypothyroidism commonly manifests as fatigue, myalgias, stiffness and slowed reflexes. We report a case of transient acute renal failure related to rhabdomyolysis and myoglobinuria in a 40 year old man that revealed the diagnosis of hypothyroidism with myopathy. The patient had proximal muscle weakness and tenderness, markedly raised muscle enzymes and deranged renal functions that normalised with thyroid replacement therapy. Hypothyroidism, though rare, should be considered a definite and authentic cause of rhabdomyolysis.
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PMID:Myoglobinuria and transient acute renal failure in a patient revealing hypothyroidism. 1077 35


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