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)

Despite frequent therapeutic use, the potential of corticosteroids to produce respiratory muscle myopathy is unknown. We studied effects of chronic steroid treatment on diaphragm mass and function. Eleven Sprague-Dawley rats were treated with cortisone acetate (100 mg.kg-1.day-1 im) for 10 days. Controls (injected with vehicle) included 11 freely eating rats and 11 animals pair fed to match food intake of cortisone rats. Steroid treatment depressed body weight 30% compared with controls. Mass of diaphragm, gastrocnemius, and extensor digitorum longus showed significant atrophy (30%); heart and soleus were unaffected. Isometric contractile properties of costal diaphragm strips were studied in vitro using direct stimulation. The force-frequency relationship was markedly depressed by steroid treatment, both at low and high frequencies. However, force developed per unit cross-sectional area was similar among all three groups, as were twitch characteristics. When stimulated every minute, forces developed by control strips fell progressively, whereas the forces of cortisone-treated strips remained unchanged. When stimulated every 5 s, the fall in force was not different between groups. We conclude that cortisone weakened the diaphragm by decreasing muscle mass but made the diaphragm more resistant to one form of fatigue in vitro.
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PMID:Diaphragm atrophy and weakness in cortisone-treated rats. 260 49

Pharmacotherapy of hypertension in the aged does not differ qualitatively but only quantitatively from that in use for younger patients. Adjusted, usually lower doses of diuretics, beta-blocking agents, ACE-inhibitors and calcium-channel blockers are the basic drugs. Individual aging processes and concomitant diseases determine the choice of drugs in the elderly (individualized therapy). All substances are initially prescribed at very low dose. The increasing infirmity of the aged often associated with tiredness, dyspnea and dizziness even without treatment requires careful instruction of the patient about effects and side effects of the prescribed medication. The old WHO-guidelines (systolic BP greater than or equal to 160, diastolic BP greater than or equal to 95 mm mercury) should be maintained for diagnosis and treatment of hypertension. However antihypertensive therapy in patients over 80 years of age and in those with marginally elevated diastolic or solely elevated systolic pressure is controversial today.
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PMID:[Hypertension and old age]. 268 25

One of the prime nutritional concerns in cancer patients is cachexia and deteriorating nutritional status. Cachexia can occur as a result of either treatment or the tumor itself. The progressive malnutrition ultimately affects performance status and organ function. Tolerance to treatment may thus be decreased, which, in turn, may adversely affect toxicity and response. In addition, the deleterious effects of malnutrition on the immune system can increase susceptibility to infection. The weakness and fatigue related to muscle wasting and changes in metabolism affect physical appearance, leading to a loss of self-esteem. Thus, the vicious cycle of cachexia severely impacts on every aspect of daily life. Providing nutritional support and effective treatment may reverse the cachexia. Studies involving caloric supplements alone have not been encouraging. Conversely, studies using megestrol acetate have shown that cancer patients gain weight and that their sense of well-being improves. However, the mechanisms of weight gain remain unknown, and further studies are needed to determine the mechanisms by which appetite is stimulated or catabolism is inhibited or both. Nursing interventions to stimulate appetite and promote greater food intake, coupled with the use of agents that alter metabolism, such as megestrol acetate, may reverse the trend of cachexia and thus provide an increased sense of well-being and improved quality of life.
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PMID:Nutritional concerns in cancer patients. 272 53

To test the value of dexamethasone acetate for ameliorating acute mountain sickness (AMS), we conducted a double-blind, randomized study that compared the effects of 4 mg of dexamethasone acetate or a placebo (given every six hours for six doses beginning at the time of exposure) at 2700 and 2050 m. Study subjects, who were recruited from health professionals who attended continuing medical education programs at ski resorts in the Rocky Mountains, were classified as having AMS when they reported three or more of the five usual symptoms (headache, insomnia, dyspnea, anorexia, and/or fatigue) on a single day. All symptoms with an intensity of at least grade 2 (moderate) out of 5 were analyzed. At 2700 m, there was a 50% decrease in the mean AMS symptom score in the dexamethasone group (0.94 +/- 1.11 vs 1.84 +/- 1.44 [mean +/- SD]) and the incidence of AMS was 20% of that in the control group (3/38 vs 14/35). At 2050 m, there was no difference between dexamethasone and a placebo in the mean AMS symptom score (1.52 +/- 1.50 vs 1.24 +/- 1.33) and the incidence of AMS (5/25 vs 4/25). Dexamethasone ameliorates the usual symptoms of AMS at 2700 m but not at 2050 m.
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PMID:Effects of dexamethasone on the incidence of acute mountain sickness at two intermediate altitudes. 291 Nov 70

One hundred twenty-eight women with advanced metastatic breast cancer were treated with a combination of aminoglutethimide (AG) (1000 mg orally, daily) and medroxyprogesterone acetate (MPA) (1500 mg orally, daily for six weeks and thereafter 500 mg orally, daily; omitting cortisone substitution). AG/MPA did not lead to side effects other than those described under AG or MPA monotherapy. Mental and personality changes seem to be more severe and frequent under combined therapy than under monotherapy. Impairment of mental functions, depressive syndromes, fatigue, ataxia, skin rash, and transient increase of gammaglutamyl transferase appeared and disappeared within the first 4 to 6 weeks of treatment. Objective remissions of at least 3 months duration from initiation of therapy were seen in 21 of 128 patients (21.9%) (3.9% complete remission [CR], 18% partial remission [PR]). A no change (NC) status occurred in an additional 25.8%. The remission duration (mean and range) was 19 (10.5-54) for CR, 16.5 (4.5-52+) for PR and 6 (3-27) months for NC patients. The highest response rate was registered for patients with only bone involvement (PR, 11; and NC, 11 of 26 patients). There was a distinct correlation of response to prior systemic treatment, receptor status of the primary tumor, disease-free interval, menopausal status, age and condition of the patient. PR was obtained in 4 of 20 patients with receptor-negative primary tumors. These results justify a prospective trial comparing AG/MPA with other forms of endocrine therapy in selected patient subgroups.
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PMID:Aminoglutethimide and medroxyprogesterone acetate in the treatment of patients with advanced breast cancer. A phase II study of the Association of Medical Oncology of the German Cancer Society (AIO). 294 73

We have measured mitochondrial ATP synthesis during passive anion influx and find that influx of phosphate leads to diminished efficiency (as reflected in the ATP:0 ratio) whereas influx of acetate produced enhanced efficiency. The anions, sulfate, propionate, and thiocyanate, are without influence on the ATP:0 ratio. It is likely that the opposite effects of phosphate and acetate on the ATP:0 ratio reflect phosphate-acetate exchange, and that acetate influx produces its positive effect on ATP synthesis by promoting phosphate efflux. Thus, phosphate efflux may be associated with increased, and phosphate influx, with decreased energy conservation.
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PMID:Influence of anion flux upon mitochondrial oxidative phosphorylation. 397 33

When Neurospora mycelium is transferred from a medium containing sucrose to one containing acetate as sole source of carbon, a preferential synthesis of many Krebs cycle, glyoxylate cycle, and associated enzymes occurs. Respiration was inhibited during preferential enzyme synthesis in the following ways. (i) The amount of aeration (shaking) was reduced, (ii) cyanide was added to the culture, (iii) the carbon source, acetate, was removed, (iv) a mutant strain was starved of its Krebs cycle intermediates, and (v) respiration was inhibited by mutation. The effect of this respiratory inhibition on the synthesis of a number of enzymes was measured. It was found that the synthesis of nicotinamide adenine dinucleotide (NAD)-linked glutamate dehydrogenase and phosphoenolpyruvate carboxykinase was significantly less inhibited under conditions of respiratory inhibition than was the synthesis of Krebs cycle, glyoxylate cycle, and most other cell proteins synthesized during the adaptation period. This differential inhibition of enzyme synthesis was almost certainly not due to differential repression by regulatory metabolic end product effectors. Inhibition of mitochondrial respiration under these conditions most likely results in a limitation of the energy supply of the cell. Thus, it is suggested that the inhibition of synthesis of most proteins after inhibition of mitochondrial respiration results from a lack of energy in a utilizable form. Possible reasons to account for the relative insensitivity of NAD-linked glutamate dehydrogenase and phosphoenolpyruvate carboxykinase to inhibition under these conditions are discussed.
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PMID:Selective inhibition of enzyme synthesis under conditions of respiratory inhibition. 509 92

Forty-five women with far-advanced metastatic breast cancer were treated with a combination of aminoglutethimide (AG), 1000 mg p.o. daily, and medroxyprogesterone acetate (MPA), 1500 mg p.o. daily. Of 41 patients evaluable for treatment response, there were two complete responses, five partial remissions, 26 patients with minor tumor responses or no change, and eight nonresponders. Major side effects included those known for AG and MPA, i.e., impairment of mental functions, depressive syndromes, fatigue, ataxia, skin rash, changes in body weight, and transient increase of gamma-glutamyl-transferase. Most side effects disappeared spontaneously after 4 to 6 weeks of treatment. Plasma hormone measurements in 28 patients revealed no impairment of adrenocorticotropic hormone and cortisol levels. In conclusion, in the AG combination, it is feasible and safe to replace cortisol by MPA. Treatment results warrant further investigation of AG-MPA in patients with breast cancer of a more favorable prognosis.
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PMID:Phase II study of aminoglutethimide and medroxyprogesterone acetate in the treatment of patients with advanced breast cancer. 612 83

Most antiandrogens appear to act by binding to the androgen receptor and competitively inhibiting the binding of testosterone and cihydrotestosterone to the receptor. Focusing on those compounds which appear to inhibit androgen receptor mediated responses, this review discusses the chemistry of those antiandrogens which have been studied to the extent that their mechanism of action is at least partially understood, outlines the mechanism of androgen action as it is currently understood and suggests how antiandrogens might fit in with this mechanism, indicates the major metabolites of several important antiandrogens, and discusses the clinical applications of several antiandrogens. Cyproterone acetate has been studied extensively as a potential male contraceptive. Although it was recognized that 100 mg of cyproterone acetate per day inhibited spermatogenesis, that dose also reduced libido and potency. Following the administration of 10 or 20 mg of cyproterone acetate per day to 15 males for 26 weeks, the following observations were made: the number of motile sperm was reduced; the quality of their motion was impaired; and the ability of the sperm to penetrate cervical mucus was decreased. Sperm density was also suppressed, but neither it nor sperm motility were inhibited to the extent necessary for contraception. Antiandrogens have been demonstrated to be beneficial in treating 5 clinical syndromes or diseases: acne, seborrhea, hirsutism with or without menstrual abnormalities; precocious puberty; benign prostatic hypertrophy; cancer of the prostate; and sexual deviates. Since 3 of these conditions are very common, effective and safe treatment would have a large market. At this time, antiandrogens are widely used in Europe for treatment of seborrhea, acne, and hirsutism and a large Veterans Administration Cooperative Study in the US was approved but has not yet been funded to compare antiandrogens with other treatments for cancer of the prostate. Studies to assess antiandrogen interaction with other hormones or drugs have been limited. Side effects in the female have been best evaluated when cyproterone acetate was administered in combination with ethinyl estradiol. In 46 women followed over 317 cycles, side effects were similar to those reported with estrogen-progestin contraceptives. Administration of 10-20 mg of cyrproterone acetate per day to males caused no significant side effects, but 100 mg or more/day has caused loss of libido, impotence, gynecomastia, tiredness, weakness, decreased efficiency, weight gain, drying and desquamation of skin over the legs, and loss of hair on the trunk and pubic area.
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PMID:Androgen antagonists in androgen target tissues. 620 9

A double-blind, crossover, randomized, placebo-controlled chronotherapeutic study was designed in which eight patients (two men, 20 and 48 yr old, and six women, 22 to 58 yr old) suffering from corticosteroid-dependent allergic asthma were socially synchronized, with a diurnal activity from about 7:30 A.M. to about 11 P.M. and a nocturnal rest. During an 8 day span they were treated on a Dutimelan 8-15 regimen, labeled DTM 8-15: at 8 A.M. a pill containing 7 mg of prednisolone acetate and 4 mg of prednisolone alcohol, at 3 P.M. a pill with 15 mg of cortisone acetate and 3 mg of prednisolone alcohol, and a placebo at 8 P.M. During another 8 day span they were given a placebo at 8 A.M. and at 3 P.M. a pill with 15 mg of cortisone acetate and 3 mg of prednisolone alcohol and at 8 P.M. another pill with 7 mg of prednisolone acetate and 4 mg of prednisolone alcohol, a regimen labeled Rx 15-20. During wakefulness (between 7 A.M. and 11 P.M.), every 2 hr at eight fixed clock hours, peak expiratory flow (PEF), grip strength, and oral temperature were self-measured and dyspnea, cough, and fatigue were self-rated. The PEF 24 hr mean as well as the nocturnal dip were lower (p less than 0.05 to p less than 0.0005) with Rx 15-20 than with DTM 8-15, while the nocturnal increase of dyspnea was greater with Rx 15-20 than with DTM 8-15. Long-term administration of corticosteroids at 8 A.M. and 3 P.M. was more effective to control asthma and enhance PEF values than the same agents and dose given at 3 and 8 P.M.
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PMID:Circadian changes in effectiveness of corticosteroids in eight patients with allergic asthma. 633 95


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