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)

We describe a patient who developed fever, fatigue, muscle weakness, dyspnea, skin rash, and eosinophilia after taking "high doses" of tryptophan for insomnia for two years. A gallium-67 scan revealed diffuse increased uptake in the lung and no abnormal uptake in the muscular distribution. Bronchoscopy and biopsy confirmed inflammatory reactions with infiltration by eosinophils, mast cells, and lymphocytes. CT scan showed an interstitial alveolar pattern without fibrosis. EMG demonstrated diffuse myopathy. Muscle biopsy from the right thigh showed an inflammatory myositis with eosinophilic and lymphocytic infiltrations.
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PMID:Gallium uptake in tryptophan-related pulmonary disease. 199 38

The eosinophilia-myalgia syndrome was first reported from New Mexico, USA, in 1989. Since then, there have been further reports from the USA, Canada and Europe. Patients with the eosinophilia-myalgia syndrome present with myalgias, morbilliform and urticarial rash, oedema, sclerodermiform lesions, fever, pneumonia, fatigue and peripheral eosinophilia (greater than 1,000/mm3). The ultimate cause is postulated to be a contamination produced by Bacterium amyloliquefaciens during the production of L-tryptophan by genetic engineering techniques. HPLC analysis revealed that the causative agent was a condensation product of 1 mole acetaldehyde and 2 moles tryptophan. Clinical and laboratory findings of the eosinophilia-myalgia syndrome, Shulman syndrome and toxic-oil syndrome are discussed.
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PMID:[Eosinophilia-myalgia syndrome]. 205 61

In E. coli WP2 trpE65 cells irradiated with UV-dose of 11 J/m2, the additional small portion of induced Trp+ mutations became resistant to photoreactivation or "dark" (excision) repair after a short-termed (10-30 min) postirradiation incubation of bacteria in a minimal medium deprived of glucose and tryptophan. Since protein synthesis could not proceed in those cells because of the lack of energy and tryptophan, the data indicate that an unknown mechanism exists which imparts some mutations with the resistance to antimutagenic repair in the absence of the inducible mutagenic system. In the light of this result, one could suggest that the normal process of mutation fixation (that is the loss of sensitivity of mutations to photoreactivation or to excision repair in cells incubated in growth medium after irradiation) should not necessarily be a direct consequence of manifestation of the activity of an inducible mutagenic system.
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PMID:[Increase in the fraction of non-repaired mutations in Escherichia coli cells, incubated in the absence of glucose after UV-irradiation]. 207 11

A phase I trial involving continuous infusion of both beta- and gamma-interferon (IFN-beta and IFN-gamma) was conducted in 20 patients in order to determine whether combinations of high doses of IFN-beta and IFN-gamma were tolerable when administered under conditions which mimic conditions of in vitro antiproliferative studies. Patients received a 5-day continuous infusion of IFN-beta/IFN-gamma, followed by a 9-day rest period. Two cycles were administered. Doses of IFN-beta/IFN-gamma were escalated between 4 dose levels, with 5 patients per dose level. Dose-dependent side effects, consisting primarily of constitutional symptoms typical of those experienced with IFN, were observed. The maximally tolerated dose of continuous IFN-beta/IFN-gamma infusion was 3 x 10(6) units of IFN-beta and 200 micrograms of IFN-gamma. Dose-limiting side effects consisted of severe headache, fatigue, fever, and hepatic toxicity. No clinical responses were observed. Serum IFN was measurable only at the highest 3 dose levels. Only 5 patients (4 at the highest dose level) had total serum levels which exceeded 50 laboratory units/ml (55, 63, 800, 800, and 550 laboratory units/ml, respectively). In order to confirm the biological effectiveness of this schedule, we measured IFN-inducible proteins prior to therapy, 24 h after the initiation of the infusion, and at the completion of the 5-day infusion. 2'-5'-Oligoadenylate synthetase, serum beta 2-microglobulin, neopterin, and p78 levels all increased significantly, and serum tryptophan decreased significantly within 24 h after the initiation of treatment (P less than 0.0001). A dose-response effect was observed for serum beta 2-microglobulin, neopterin, and p78 (P less than 0.02). We retrospectively compared the results of this trial with those of another IFN-beta/IFN-gamma trial in which IFN-beta and IFN-gamma were administered by i.v. bolus. Within the limitations of a retrospective comparison, continuous infusion was less well tolerated than our previous schedule of bolus administration 3 times/week. However, the continuous infusion schedule appeared to be more effective in enhancing 2'-5'-oligoadenylate synthetase levels in mononuclear cells. We conclude that tolerable doses of IFN-beta and IFN-gamma do not result in serum IFN levels which produce significant synergistic antiproliferative responses in vitro. This study and other findings suggest that, unless higher doses can be achieved, combinations of IFN-beta and IFN-gamma are unlikely to have significant therapeutic activity.
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PMID:Biological and clinical effects of the combination of beta- and gamma-interferons administered as a 5-day continuous infusion. 211 42

The present paper reviews evidence for the role of specific amino acids in the etiology of fatigue and the overtraining syndrome in athletes. An increase in the plasma concentration ratio of free tryptophan: branched-chain amino acids may mediate an increase in 5-HT synthesis in the brain and thus induce fatigue during exercise. Glutamine is essential for the proper functioning of cells of the immune system and a decrease in plasma glutamine concentration post-exercise and in overtraining may induce an impairment in immune function. Branched-chain amino acids may play a central role in both these processes. Thus, they compete with free tryptophan for entry into the brain. Branched-chain amino acids may also be important precursors of nitrogen for the synthesis of glutamine in skeletal muscle or important in the control of glutamine release from muscle. Consequently, the metabolism of glutamine, tryptophan, and branched-chain amino acids may be the key to understanding some aspects of central fatigue and some aspects of immunosuppression that are very relevant to athletic endeavor. They may be also relevant to other physiological and pathological conditions.
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PMID:A communicational link between skeletal muscle, brain, and cells of the immune system. 219 90

A young, previously healthy woman presented with increasing muscle pain, lower limb swelling, fatigue and eosinophilia. She had consumed L-tryptophan tablets (one to two at night) over the preceding five months for management of her insomnia. Her condition slowly deteriorated and she developed generalised oedema and severe lethargy. A white blood cell count was 21.3 x 10(9)/L with 43% eosinophils (Normal range: 4.0-11.0 x 10(9)/L with 1-6% eosinophils. A biopsy specimen of the deep fascia and gastrocnemius muscle demonstrated fasciitis and myositis. The patient failed to recover after cessation of L-tryptophan use but her condition improved rapidly without significant sequelae after systemic treatment with corticosteroids.
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PMID:Eosinophilia-myalgia syndrome associated with L-tryptophan use. 199 19

Eight patients who became ill while taking tryptophan had myalgia, fatigue, rash, fever, edema, alopecia, arthralgias, diminished joint motion, skin tightening, muscle cramping, and distal paresthesias. Three had shortness of breath, and one had pulmonary hypertension. Laboratory abnormalities included peripheral eosinophilia, leukocytosis, thrombocytosis, raised erythrocyte sedimentation rate, and elevated serum levels of aldolase, lactate dehydrogenase, and liver enzymes. Of 4 chest radiographs, 3 were abnormal. Of 5 skin and muscle biopsies, 4 showed sclerosis or mixed inflammatory cell infiltration of the dermis, subcutis, and fascia. Eosinophils were often present, but vasculitis was absent. Muscle inflammation was minimal. We conclude that the "eosinophilia-myalgia syndrome" is related to the ingestion of tryptophan and that abnormalities in the secretion of lymphokines may be important in its pathogenesis.
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PMID:Tryptophan-induced eosinophilia-myalgia syndrome. 221 1

Four patients fulfilling the case definition for eosinophilia-myalgia syndrome are described, including one whose disease began in 1986. Each displayed a variety of symptoms: one suffered principally from myalgia and recovered spontaneously on discontinuation of L-tryptophan therapy; one exhibited progressive sclerodermiform skin changes, neuropathy, and myopathy; a third had prominent neuromuscular disease and sclerodermiform skin changes; and the fourth experienced profound weight loss, an axonal polyneuropathy, and perivascular lymphoid infiltrates simulating a lymphoma. Evidence of T-cell activation was present in peripheral blood and affected tissues during the clinically active progressive phase of disease. Among other manifestations pleural effusion, cutaneous vasculitis, joint contractures, and bloody diarrhea were observed. A history of L-tryptophan ingestion should be sought in patients with myalgia, fatigue, or the above outlined symptoms.
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PMID:Eosinophilia-myalgia syndrome associated with L-tryptophan ingestion. Analysis of four patients and implications for differential diagnosis and pathogenesis. 217 45

The eosinophilia-myalgia syndrome associated with the use of oral preparations of the amino acid L-tryptophan was recognized in late 1989. We describe the clinical and laboratory manifestations, pathological findings and early clinical course of 20 patients with the eosinophilia-myalgia syndrome. Prominent clinical findings included severe myalgias limiting function, fatigue, rashes, edema and weight gain, weight loss, muscle weakness and shortness of breath. Laboratory findings included eosinophilia (often marked), normal erythrocyte sedimentation rate, and elevated aldolase with normal or low creatine kinase values. On biopsy fascial inflammation was always seen consisting of lymphocytes, histiocytes and eosinophils in a perivascular distribution. Invasion of the vascular wall by lymphocytes was seen in 20%. Capillary and arteriolar endothelial cell thickening was found in most cases on electron microscopy and endothelial cell necrosis or mural invasion by lymphocytes was seen in 25% of cases. Two patients improved with no therapy. Ten patients responded to therapy with prednisone alone. Three patients have had progressive disease and one of these died. The relationship of this syndrome to previously described disease entities associated with eosinophilia is discussed.
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PMID:Eosinophilia-myalgia syndrome associated with L-tryptophan use. 227 99

In both trained and untrained rats, exercise increased the plasma concentration ratio of aromatic amino acids to branched-chain amino acids which might favour entry of the aromatic amino acids into the brain. Exercise in trained rats did not change the brain concentration of 5-hydroxytryptamine but increased that of 5-hydroxyindole acetic acid. Exercise in the untrained rat increased the concentration of brain tryptophan and that of 5-hydroxytryptamine but that of 5-hydroxyindole acetic acid was unchanged. The increased concentration of 5-hydroxytryptamine in untrained rats might be involved in central fatigue.
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PMID:Effect of sustained exercise on concentrations of plasma aromatic and branched-chain amino acids and brain amines. 242 44


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