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)

Fourteen patients with different advanced solid tumors were treated by intratumoral application of recombinant human tumor necrosis factor alpha. In five patients, local tumor regression occurred. However, the duration of response was short, implying a rapid development of resistance to rTNF-alpha application. The main clinical side-effects, including chills, fever, anorexia and fatigue, were similar to systemic rTNF-alpha treatment. Cardiovascular, pulmonary or metabolic toxicities were not observed. This study demonstrates that a high concentration of rTNF-alpha at the tumor site has the potential to induce local tumor regressions and, therefore, seems more reasonable for further clinical investigations, especially in combination with other cytokines.
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PMID:Intralesional application of recombinant human tumor necrosis factor alpha induces local tumor regression in patients with advanced malignancies. 253 93

Fifteen patients with advanced metastatic adenocarcinomas were treated in a phase-I study with continuous intravenous 24 h infusion of recombinant tumor necrosis factor alpha (TNF-alpha) in order to determine the maximum tolerated dose (MTD) and associated side-effects. Patients received 40-400 micrograms/m2 TNF-alpha once (arm A) or twice (arm B) weekly for a scheduled treatment period of 2 months. The observed systemic side-effects resembled those reported for interferons and included fever, chills, fatigue, headaches, myalgias, thrombocytopenia, prostration, and malaise. Dose-limiting toxicities, resulting in a median MTD of 200 micrograms/m2 for 24 h, were fever, chills, fatigue, myalgias, and thrombocytopenia. Out of 15 patients, 11 showed tumor progression, and 3 sustained in no change for over 2 months of treatment. A minor response was seen in 1 patient with a colorectal carcinoma and liver metastases. To reduce side-effects, patients were treated either with paracetamol or indomethacin. Higher MTDs were observed in patients treated with indomethacin. No detectable plasma TNF-alpha levels or TNF antibodies were measured under therapy (plasma TNF-alpha less than 20 pg/ml). We conclude that TNF-alpha appears to have some antineoplastic activity in patients with adenocarcinomas since 4 patients remained in no change or showed a minor response.
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PMID:Phase-I trial of intravenous continuous infusion of tumor necrosis factor in advanced metastatic carcinomas. 265 35

It is generally assumed that noises have a detrimental effect when the cochlear receptor is overloaded and, more specifically, when the cochlear microphonic (CM) fails to increase linearly with intensity. In order to investigate further the relations between the nonlinearity of CM and damage to the cochlea, a series of experiments was carried out on guinea pigs to relate the short-term CM depression following the presentation of noises or tones with the nonlinearity and the assymmetry. The asymmetrical non-linearity of CM was measured in tracing the input-out functions and also the wave-forms. Two other important tests of the asymmetrical nonlinearity were used: the measure of interference and of summating potential (SP DIF). The results show that the fatigability is greater when there is a large negative asymmetry or a large negative SP. Variations in asymmetry and in SP were observed among individuals. Other changes of symmetry were provoked by asphyxia or by introducing solutions of KCl in the perilymph. These changes were well correlated with the fatigability. These results are interpreted in a model of the cochlear transducer derived from the model of Davis. The assymetry of a flux of potassium ions between endolymph and the hair cells is assumed to be responsible for the alterations associated with cochlear fatigue and trauma.
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PMID:Relations between cochlear fatigue and the asymmetrical nonlinearity of the cochlear microphonics. 736 35

Chronic fatigue syndrome (CFS) is an idiopathic disorder characterized by fatigue that is markedly exacerbated by physical exertion. In the present study, we tested the hypothesis that mild exercise (walking 1 mph [1 mile = 1.609 km] for 30 min) would provoke serum cytokine and cerebral blood flow abnormalities of potential pathogenic importance in CFS. Interleukin-1 beta, interleukin-6, and tumor necrosis factor alpha were nondetectable in sera of CFS patients (n = 10) and healthy control subjects (n = 10) pre- and postexercise. At rest, serum transforming growth factor beta (TGF-beta) levels were elevated in the CFS group compared with the control group (287 +/- 18 versus 115 +/- 5 pg/ml, respectively; P < 0.01). Serum TGF-beta and cerebral blood flow abnormalities, detected by single-photon emission-computed tomographic scanning, were accentuated postexercise in the CFS group. Although these findings were not significantly different from those in the control group, the effect of exercise on serum TGF-beta and cerebral blood flow appeared magnified in the CFS patients. Results of this study encourage future research on the interaction of physical exertion, serum cytokines, and cerebral blood flow in CFS that will adopt a more rigorous exercise program than the one used in this study.
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PMID:Effects of mild exercise on cytokines and cerebral blood flow in chronic fatigue syndrome patients. 749 49

In recent years, thalidomide has been used for the treatment of a variety of ulcerative and immunologic conditions. Several previous reports have suggested that thalidomide therapy is beneficial for patients with aphthous ulceration related to human immunodeficiency virus (HIV) infection. We describe the use of thalidomide in 20 HIV-infected patients with oropharyngeal, esophageal, and rectal ulceration. Nineteen patients had a dramatic response to thalidomide therapy, with both subjective and objective abatement in the signs and symptoms of their ulcerative disease. The standard treatment course was 200 mg of thalidomide for 14 days (the drug was administered at night). Four patients required additional courses of treatment because symptoms recurred after thalidomide therapy was stopped. Side effects due to thalidomide included rash (5 patients), peripheral neuropathy (1 patient), and excessive fatigue (1 patient). There did not appear to be any adverse immunologic effects in thalidomide-treated patients. The mechanism of the effect of thalidomide is uncertain, although recent studies have suggested that thalidomide selectively inhibits the production of tumor necrosis factor alpha.
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PMID:Thalidomide as treatment of refractory aphthous ulceration related to human immunodeficiency virus infection. 774 24

We tested the hypothesis that increases in tumor necrosis factor alpha (TNF-alpha) induced by human immunodeficiency virus (HIV) are associated with the increases in slow-wave sleep seen in early HIV infection and the decrease with sleep fragmentation seen in advanced HIV infection. Nocturnal sleep disturbances and associated fatigue contribute to the disability of HIV infection. TNF-alpha causes fatigue in clinical use and promotes slow-wave sleep in animal models. With slow progress toward a vaccine and weak effects from current therapies, efforts are directed toward extending productive life of HIV-infected individuals and shortening the duration of disability in terminal illness. We describe previously unrecognized nocturnal cyclic variations in plasma levels of TNF-alpha in all subjects. In 6 of 10 subjects (1 control subject, 3 HIV-seropositive patients with CD4+ cell number > 400 cells per microliters, and 2 HIV-positive patients with CD4+ cell number < 400 cells per microliters), these fluctuations in TNF-alpha were coupled to the known rhythm of electroencephalogram delta amplitude (square root of power) during sleep. This coupling was not present in 3 HIV-positive subjects with CD4+ cell number < 400 cells per microliters and 1 control subject. In 5 HIV subjects with abnormally low CD4+ cell counts ( < 400 cells per microliters), the number of days since seroconversion correlated significantly with low correlation between TNF-alpha and delta amplitude. We conclude that a previously unrecognized normal, physiological coupling exists between TNF-alpha and delta amplitude during sleep and that the lessened likelihood of this coupling in progressive HIV infection may be important in understanding fatigue-related symptoms and disabilities.
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PMID:Sleep electroencephalogram delta-frequency amplitude, night plasma levels of tumor necrosis factor alpha, and human immunodeficiency virus infection. 861 48

Interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) are proinflammatory cytokines which may be involved in the pathogenesis of MS. IFN-alpha counteracts many of the proinflammatory actions of IFN-gamma and TNF-alpha. We treated 20 patients with relapsing-remitting (RR) MS with 9 MIU of recombinant IFN-alpha-2a (rIFN-alpha) (n = 12) or placebo (n = 8) intramuscularly every other day for 6 months. Clinical exacerbations or new or enlarging lesions at serial MRI occurred in 2/12 rIFN-alpha-treated and in 7/8 placebo-treated patients (P < 0.005). Only one new MRI lesion was detected in the rIFN-alpha group, while 27 new or enlarging lesions were detected in placebo group (P < 0.01). Baseline lymphocyte IFN-gamma (19.10 +/- 7.12 U ml-1) and TNF-alpha (18.05 +/- 5.34 pg ml-1) production significantly decreased to 3.03 +/- 0.66 (P < 0.04) (for IFN-gamma) and to 5.78 +/- 0.90 (P < 0.04) (for TNF-alpha) after rIFN-alpha treatment. IFN-gamma and TNF-alpha production was unchanged in the placebo group. rIFN-alpha was tolerated without drop-outs or serious side-effects, but fever, malaise, fatigue (interfering with daily activities in two patients) and leukopenia frequently occurred. High-dose chronic systemic rIFN-alpha might reduce clinical and MRI signs of disease activity in RRMS. The changes in cytokine production suggest that the effect is probably mediated by a down-regulation of proinflammatory cytokine.
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PMID:Interferon alpha treatment of relapsing-remitting multiple sclerosis: long-term study of the correlations between clinical and magnetic resonance imaging results and effects on the immune function. 934 96

Obesity is associated with an increased incidence of infection, diabetes, and cardiovascular disease, which together account for most obesity-related morbidity and mortality. Decreased expression of leptin or of functional leptin receptors results in hyperphagia, decreased energy expenditure, and obesity. It is unclear, however, whether defective leptin-dependent signal transduction directly promotes any of the conditions that frequently complicate obesity. Abnormalities in tumor necrosis factor alpha expression have been noted in each of the above comorbid conditions, so leptin deficiency could promote these complications if leptin had immunoregulatory activity. Studies of rodents with genetic abnormalities in leptin or leptin receptors revealed obesity-related deficits in macrophage phagocytosis and the expression of proinflammatory cytokines both in vivo and in vitro. Exogenous leptin up-regulated both phagocytosis and the production of proinflammatory cytokines. These results identify an important and novel function for leptin: up-regulation of inflammatory immune responses, which may provide a common pathogenetic mechanism that contributes to several of the major complications of obesity.
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PMID:Leptin regulates proinflammatory immune responses. 943 11

Postdialysis fatigue (PDF) has been ascribed to excessive ultrafiltration and decline in osmolality during hemodialysis. We evaluated the potential role for the sommogenic cytokines, interleukin-1 beta (IL-1beta) and tumor necrosis factor alpha (TNFalpha), in the genesis of PDF Patients dialyzing with cuprophane membrane were assigned to PDF (N=25) and non-PDF (N=25) groups based on a fatigue index questionnaire. Pre- and postdialysis samples were obtained from 3 consecutive treatments and later assayed for serum levels of IL-1beta and TNFalpha by ELISA. Our results show significant intradialytic elevation of TNFalpha in both non-PDF groups (non-PDF: pre- 3.36+/-0.80 pg/ml to post 3.75+/-0.88 pg/ml, p<0.04; PDF: pre- 5.95+/-0.80 pg/ml to post- 8.66-/+1.35 pg/ml, p<0.02). The degree of intradialytic augmentation was significantly greater for TNFalpha in the PDF group (46+/-18% vs 11+/-5%; p<0.03). There were no significant intradialytic changes in serum levels of IL-1beta in either the PDF or non-PDF groups. There also were no significant differences in dialysis-related body weights, systolic blood pressures, or osmolalities. These findings suggest that TNFalpha may be involved in the pathogenesis of PDF.
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PMID:Elevated levels of tumor necrosis factor alpha in postdialysis fatigue. 956 29

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


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