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)

Zidovudine-induced myopathy is characterized by reversible muscle weakness, wasting, myalgia, fatigue, and elevated creatine kinase (CK). Some zidovudine-treated patients with normal muscle strength experience excessive fatigue, myalgia, or transient mild CK elevations that improve when zidovudine is stopped. To determine the cause of these symptoms, we studied 13 physically fit, HIV-infected men who developed fatigue, myalgia, and reduced endurance, while taking zidovudine for a mean period of 20 months (2-39 months), with neurological evaluation and muscle biopsy processed for enzyme histochemistry and electron microscopy (EM). All subjects had normal muscle strength. In 6 of the 13 patients, muscle biopsies were normal by enzyme histochemistry. EM, however, demonstrated proliferation of normal or abnormal mitochondria, and increased amounts of lipid, glycogen, and lipofuscin. Electromyographic (EMG) studies (5/5) and serum CK (6/6) were normal. The other 7 individuals had signs of moderate to severe mitochondrial abnormalities shown by both light microscopy and EM, characterized by severe destruction, vacuolization, and rare paracrystalline inclusions. Most had elevated CK (4 out of 7) and normal EMG (5 out of 7). The severity of morphological abnormalities did not correlate with duration of HIV infection, zidovudine therapy, or zidovudine dosage. We conclude that in zidovudine-treated patients, symptoms of fatigue, myalgia, reduced endurance, and exercise intolerance represent early signs of zidovudine-induced mitochondriotoxicity, which causes an energy shortage within the muscle fibers even when muscle strength is still normal. Zidovudine, a DNA chain terminator, results in overt myopathy when a critical threshold of molecular, histological, and biochemical dysfunction of mitochondria is crossed, which seems to vary between individuals.
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PMID:Early features of zidovudine-associated myopathy: histopathological findings and clinical correlations. 757 71

A 60-year-old man with wasting and weakness of the right hand following ulnar nerve entrapment at the elbow was referred for electrotherapy. An ulnar nerve transposition had been performed 2 years previously. This had produced some improvement in nerve conduction without significantly improving hand muscle function. The right first dorsal interosseous muscle (FDI) was stimulated for 4 hours per day over a 6-week period with a stimulus pattern replicating the discharge of a single motor unit from a healthy, fatigued FDI (patterned neuromuscular stimulation or PNMS). The response was assessed using a single case design. Significant improvements in the strength and fatigue resistance of the FDI were observed, associated with improvements in general hand function. PNMS may be useful in restoring hand function in patients with muscle atrophy following entrapment neuropathy.
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PMID:The use of patterned neuromuscular stimulation to improve hand function following surgery for ulnar neuropathy. 796 92

The cancer cachexia syndrome is clinically characterized by anorexia, wasting, weight loss, weakness, fatigue, poor performance status, and impaired immune function, which are unresolved by forced caloric intake. Diminished nutritional intake, maladaptive metabolic processes, and increased metabolic expenditure all play roles in the development of this syndrome. Multiple mediators of both tumor and host cell origin are mechanistic in its etiology. Treatment is not entirely satisfactory and should be directed toward improvement in the quality of life of the patient and should often include nutritional counseling. It should take into consideration both disease and treatment related factors as well as the cachexia syndrome itself. Use of progestogens (megesterol acetate, medroxyprogesterone), corticosteroids (decadron, prednisone), metoclopramide, tetrahydrocannabinol (dronabinol), and possibly anabolic steroids (nandrolone decanoate, oxandrolone), melatonin, and eicosapentaenoic acid, may yield therapeutic benefit.
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PMID:The cancer cachexia syndrome. 920 84

Despite progress in leukemia therapy, only 20-30% of patients with acute myelogenous leukemia (AML) are cured. 1-beta-D-arabinofuranosylcytosine- and topoisomerase II-reactive drugs are the primary therapeutic agents used. The aim of this study was to evaluate the potential activity of tallimustine in leukemia. In this study, we first investigated the efficacy and toxic effects of tallimustine, a distamycin-A derivative, in a human leukemia model in severe combined immunodeficient (SCID) mice. On the basis of its dramatic activity in this preclinical study, a Phase I study of tallimustine at a starting dose of 300 microgram/m2/day for 3 days every 3-4 weeks was conducted in patients with refractory or relapsed leukemia. In SCID mice grafted with a human myelomonocytic leukemia cell line, tallimustine resulted in complete remission of disease in most mice at tolerable dosages ranging from 0.86 to 3.0 mg/kg/day for 3 days and was combined effectively and safely with a 2-day schedule of high-dose ara-C. In the Phase I study, 26 patients with refractory or relapsed leukemia were treated. The maximum tolerated dose was 900 microgram/m2/day for 3 days every 3-4 weeks. This dose was 3 times higher than the maximum tolerated dose in solid tumors and was limited by severe mucositis. Magnesium and potassium wasting were also observed, but other side effects (fatigue and gastrointestinal) were minor. Two (8%) patients with AML achieved complete remission and two achieved hematological improvement with persistent thrombocytopenia. The results of this study indicate that tallimustine has promising activity in AML. Future studies may combine tallimustine with other agents known to be active against AML, and investigate its activity in other hematological malignancies. The recommended Phase II single-agent dose of tallimustine is 750-900 microgram/m2/day for 3 days, and combination studies may start at 50-66% of this dose schedule. The SCID mouse model of human leukemia may be promising in the preclinical evaluation and selection of potential antileukemic agents.
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PMID:Tallimustine, an effective antileukemic agent in a severe combined immunodeficient mouse model of adult myelogenous leukemia, induces remissions in a phase I study. 981 37

There is a high prevalence of protein-energy malnutrition in both nondialyzed patients with advanced chronic renal failure and in those individuals with end-stage renal disease who are receiving maintenance hemodialysis or chronic peritoneal dialysis therapy. Approximately one-third of maintenance dialysis patients have mild to moderate protein-energy malnutrition, and about 6 to 8 percent of these individuals have severe malnutrition. These statistics are of major concern because markers of protein-energy malnutrition are strong predictors of morbidity and mortality. The causes of protein-energy malnutrition in patients with chronic renal failure include: (1) decreased energy or protein intake; (2) concurrent chronic illnesses, and superimposed acute illnesses and possibly increased inflammatory cytokines; (3) the catabolic stimulus of hemodialysis; (4) losses of nutrients into dialysate, particularly amino acids, peptides, protein (with peritoneal dialysis), glucose (when hemodialysis is performed with glucose-free dialysate) and water-soluble vitamins; and (5) diagnostic or therapeutic (e.g., prednisone therapy) procedures that reduce nutrient intake or engender net protein breakdown. Other theoretically possible causes for protein-energy malnutrition include (6) chronic blood loss; (7) endocrine disorders (especially resistance to insulin and insulin-like growth factor-I, hyperglucagonemia, hyperparathyroidism and deficiency of 1,25-dihydroxycholecalciferol); (8) products of metabolism that accumulate in renal failure and may induce wasting, such as organic and inorganic acids; (9) loss of the metabolic actions of the kidney; and (10) the accumulation of toxic compounds that are taken up from the environment (e.g., aluminum).
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PMID:Pathophysiology of protein-energy wasting in chronic renal failure. 991 8

Chronic heart failure (CHF) is a complex syndrome affecting many body systems. Body wasting (ie, cardiac cachexia) is a serious complication of CHF long known but little investigated. Although no specific diagnostic criteria have been established, we have suggested that cardiac cachexia be defined on the basis of the presence of documented nonintentional and nonedematous weight loss > 7.5% of the premorbid normal weight, occurring over a time period of > 6 months. Using this definition, 16% of an unselected CHF outpatient population was found to be cachectic. The cachectic state is predictive of impaired prognosis independently of age, functional disease classification, left ventricular ejection fraction, and peak oxygen consumption. The mortality in the cachectic cohort is 50% at 18 months. Analyzing body composition in detail, it has been found that patients with cardiac cachexia suffer from a general loss of fat tissue (ie, energy reserves), lean tissue (ie, skeletal muscle), and bone tissue (ie, osteoporosis). Cachectic CHF patients are weaker and fatigue earlier, which is due to both reduced skeletal muscle mass and impaired muscle quality. The pathophysiologic alterations leading to cardiac cachexia remain unclear, but initial cross-sectional studies have suggested that humoral neuroendocrine and immunologic abnormalities are linked, independently of established heart failure severity markers, to the presence of body wasting. Comparing the features of cachectic and noncachectic CHF patients with those of healthy control subjects, it is mainly the cachectic CHF patients who show raised plasma levels of epinephrine, norepinephrine, and cortisol; the highest plasma renin activity and aldosterone plasma concentrations; and the lowest plasma sodium level. Several studies have shown that cardiac cachexia is linked to raised plasma levels of tumor necrosis factor-ac. The degree of body wasting is strongly correlated with neurohormonal and immune abnormalities. The available evidence suggests that cardiac cachexia is a multifactorial neuroendocrine and metabolic disorder with a poor prognosis. A complex imbalance of different body systems may cause the development of body wasting.
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PMID:Cardiac cachexia: a syndrome with impaired survival and immune and neuroendocrine activation. 1008

Body wasting, i.e, cardiac cachexia, is a complication of chronic heart failure (CHF). The authors have suggested that cardiac cachexia should be diagnosed when nonedematous weight loss of more than 7.5% of the premorbid normal weight occurs over a time period of more than 6 months. In an unselected CHF outpatient population, 16% of patients were found to be cachectic. The cachectic state is predictive of poor survival independently of age, functional class, ejection fraction, and exercise capacity. Patients with cardiac cachexia suffer from a general loss of fat, lean, and bone tissue. Cachectic CHF patients are weaker and fatigue earlier. The pathophysiologic causes of body wasting in patients with CHF remain unclear, but initial studies have suggested that humoral neuroendocrine and immunologic abnormalities may be of importance. Cachectic CHF patients show increased plasma levels of catecholamines, cortisol, and aldosterone. Several studies have shown that cardiac cachexia is linked to increased plasma levels of tumor necrosis factor alpha. The degree of body wasting is strongly correlated with neurohormonal and immune abnormalities. Some investigators have suggested that endotoxin may be important in triggering immune activation in CHF patients. Available studies suggest that cardiac cachexia is a multifactorial neuroendocrine and immunologic disorder that carries a poor prognosis. A complex catabolic-anabolic imbalance in different body systems may cause body wasting in patients with CHF.
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PMID:Insights into the pathogenesis of chronic heart failure: immune activation and cachexia. 1035 92

A nationwide search of patients with classical 21-hydroxylase deficiency (21-OHD) was performed in Finland to determine the long-term outcome of the disease. In total, 108 patients were found. Fifty-four patients (50%, 31F, 23M) had deficiency of a salt-wasting form and another 54 (50%, 29F, 25M) had a simple virilizing form of 21-OHD. A significant number of severe complications suggestive of glucocorticoid deficiency was found. There were five deaths (4.6% of all) possibly connected with cortisol deficiency. Ten additional patients (9.3% of all) had been acutely admitted 14 times in all due to symptoms of glucocorticoid deficiency. These symptoms included sudden loss of consciousness, convulsions and severe fatigue. Afterwards, permanent neurological defects were detected in two of these patients. Finally, a cross-sectional study was carried out to establish an estimate of the long-term outcome of the disease. Thirty-two (55%) of the 58 patients aged 16 y or more participated in this study. The patient group did not differ from the general Finnish population in terms of education. Three of the patients (5%) had retired prematurely. Surprisingly, the patients felt that their health-related quality of life, as reported in the RAND-36 questionnaire, was better than that of the general Finnish population (p = 0.023). However, as a significant number of all patients did not participate in this study, the quality of life evaluation results must be interpreted with caution. In conclusion, a significant number of complications was found among patients treated for classical 21-OHD. Nevertheless, the disease has a favourable outcome in terms of quality of life.
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PMID:Long-term outcome of classical 21-hydroxylase deficiency: diagnosis, complications and quality of life. 1070 88

Camurati-Englemann syndrome (DPD1) is an autosomal dominant condition associated with progressive cortical sclerosis of the diaphyses of all the long bones. Clinical features include abnormal gait, muscle weakness and wasting, and generalized fatigue. The DPD1 gene was recently mapped to a 15.1-cM region on chromosome 19q13.2. We have narrowed the region containing the DPD1 gene to a 3.2-cM region flanked by short tandem repeat markers, D19S881 and D19S718. TGFB1, a candidate gene mapped within this region, was excluded.
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PMID:Confirmation of the mapping of the Camurati-Englemann locus to 19q13. 2 and refinement to a 3.2-cM region. 1084 14

The diagnosis of cancer has traditionally been associated with malnutrition and wasting. Oncology patients are at risk for nutrition-related problems because of the cancer itself, as well as the treatment prescribed. Clinical manifestations of cachexia include anorexia, weight loss, muscle wasting, and fatigue, resulting in poor performance status. Control of symptoms, such as anorexia, nausea and vomiting, and mucositis is imperative in the management of cancer cachexia. Current pharmacologic therapies, as well as complementary and alternative methods, are presented. The nurse plays a key role in ensuring that the nutritional needs of oncology patients are met.
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PMID:Management of cancer cachexia. 1128 21


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