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)

Twenty-five patients with metastatic carcinoma were entered into a Phase I clinical trial using poly(I,C)-LC at either 1 mg/m2 or 4 mg/m2 intravenous, twice weekly, for 4 weeks. None of the 15 patients entered at the 1 mg/m2 dose had an objective response; three had progressive disease. Similarly, no objective responses were observed among the 10 patients treated at the 4 mg/m2 dose of poly(I,C)-LC; one patient was removed from the study due to progressive disease. Toxicities observed at the 1 mg/m2 dose were mild hypotension, fever, nausea, vomiting, fatigue, and headache. The first patient treated at the 4 mg/m2 dose was taken off of the study for severe hypotension. In the subsequent nine patients treated at this dose, a pretreatment with one dose at 1 mg/m2 was given, and no further problems with hypotension were encountered. The other toxicities at 4 mg/m2 were similar to those seen at 1 mg/m2.
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PMID:A phase I evaluation of poly(I,C)-LC in cancer patients. 241 63

All major types of human interferons (IFNs) have been purified and clinically administered as antitumor agents. We summarize here experience to date with toxicity of IFNs in cancer patients. The acute syndrome consists of fever, chills, myalgias, arthralgias, and headache, with some variation according to type of IFN, route of administration, schedule, and dose. Fatigue, perhaps reflecting CNS toxicity, is the most prevalent nonacute symptom. At high doses, IFNs are neurotoxic; the abnormalities seen by EEG resemble those in diffuse encephalitis. Hematologic toxicity consists mainly of leukopenia, but anemia and thrombocytopenia occur in some patients. Nausea, vomiting, and diarrhea are the main gastrointestinal symptoms. Elevation of serum transaminases seems to reflect liver toxicity. Renal function is well preserved, except for rare instances of acute renal failure. Cardiac toxicity remains questionable, although heart failure and arrhythmias have been associated with the administration of IFNs. Most, if not all, of these effects are reversible or can be ameliorated. With IFN alpha, the type most widely used in clinical studies, doses of 1 million to 9 million units (MU) are generally well tolerated, but doses greater than or equal to 18 MU yield moderate to severe toxicity. Doses greater than or equal to 36 MU can induce severe toxicity and significantly alter the performance status of the patient.
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PMID:Clinical toxicity of interferons in cancer patients: a review. 241 69

Many drugs are applied in local treatment for skin malignant tumors. These drugs are living-BCG, OK-432, MY-1, WPG, interferon preparation (alpha, beta and gamma), TNF, IL-2, peplomycin, bleomycin and others. Some of them already have completed clinical trials and others are under clinical observation. In local administration of these drugs, skin lesions (malignant melanoma, CTL-mainly mycosis fungoides, carcinoma in situ and others) show good improvement. The effects were more observed in the tumors with diameters of 1 cm or less and appeared 3 to 10 injections in most cases. As complications, there are fever, general fatigue, vomiting, anorexia, leucopenia and others. Among them, the fever was most observed immediately after injections without any more severe complications. It may be concluded that treatment by intratumoral administration is useful for skin malignant tumors.
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PMID:[Clinical effects induced by intratumoral administration of anti-cancerous drugs in skin malignant tumors]. 246 39

To investigate the pharmacokinetics and effects of intravenous foscarnet, 13 relatively healthy male patients with human immunodeficiency virus infection and a mean CD4+ lymphocyte value of 0.45 x 10(-9) cells per liter were given a continuous intravenous infusion of foscarnet (0.14 to 0.19 mg/kg per min) for 8 to 21 days. Blood and urine samples were taken during and after drug administration to monitor foscarnet concentrations. Lumbar puncture was performed during the infusion in five patients. The concentrations in plasma showed large variations both within and between patients. The disposition of foscarnet could be explained by a triexponential equation (t1/2 lambda 1, 0.40 to 2.52 h; t1/2 lambda 2, 3.20 to 16.7 h; t1/2 lambda 3, 36 to 196 h). Renal clearance accounted for most of the plasma clearance, the difference probably reflecting the passage of foscarnet into bone. Up to 20% of the cumulative dose may have been deposited in bone 7 days postinfusion. Foscarnet was distributed to the cerebrospinal fluid in a concentration varying from 13 to 68% of the simultaneous concentration in plasma. Polyuria and polydipsia were recorded in all patients. There appears to be an association between the degree of malaise, including symptoms such as nausea, vomiting, fatigue, and headache, and concentrations in plasma above 350 mumol/liter.
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PMID:Pharmacokinetics of foscarnet and distribution to cerebrospinal fluid after intravenous infusion in patients with human immunodeficiency virus infection. 252 39

Corticotrophin (ACTH) deficiency is an important cause of a potentially lethal form of adrenocortical failure. Difficulties can arise in making the diagnosis, especially when secretion of other pituitary trophic hormones is normal. Presenting features of seven patients with ACTH deficiency, in whom the diagnosis was difficult for a variety of reasons, are reported and discussed. Two patients had a normal cortisol response to synthetic ACTH. The possibility of ACTH deficiency should be considered in any patient presenting with weight loss, vomiting, muscular fatigue and stiffness, hyponatraemia or hypoglycaemia.
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PMID:ACTH deficiency: problems in recognition and diagnosis. 254 52

The purpose of this study was to identify variables useful for predicting a positive response to the tricyclic antidepressant desipramine, amongst bulimic subjects. Using a randomized double-blind cross-over design, 24 normal weight bulimics completed a 15-week protocol in which they received either desipramine (150 mg/day) for six weeks, no drug for three weeks, followed by placebo for six weeks, or the reverse sequence. At weeks 0, 2, 4, 6, 9, 11, 13, and 15, each subject was assessed using the EDI, SCL-90, POMS and binge records. The DST, Diagnostic Interview Schedule (DIS), and a personal and family medical-psychiatric history questionnaire were administered at initial assessment, while plasma desipramine levels were obtained at weeks 4 and 13. Responders were defined in terms of both binge frequency reduction, and decrease in depressive symptoms. In the sample of 24 subjects, desipramine was significantly more effective than placebo in reducing the frequency of weekly binging and vomiting, as well as causing a reduction in the fatigue scale of the POMS. No significant effect of the drug was obtained on the EDI or the SCL-90. In terms of reduction in binge frequency, seven responders were identified; another seven were found to be borderline responders, while 10 were labeled as non-responders. The three groups did not differ in terms of their initial scores on the SCL-90, POMS, DST, DIS results, or psychological subscales of the EDI. However, responders were found to have lower EDI bulimia subscale scores, but a higher frequency of purging episodes than were non-responders. Eight patients were identified as borderline responders with respect to depressive symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Bulimia: independence of antibulimic and antidepressant properties of desipramine. 264 70

Fluoxetine, a selective inhibitor of 5-HT uptake, was compared to dothiepin in a double-blind study of 6 weeks duration in 100 depressed patients (male and female) drawn from 8 general practices. Only those who scored at least 17 on the first 17 questions of the Hamilton Psychiatric Rating Scale for Depression (HAM-D) were selected. Both groups improved throughout the trial, though the dothiepin treated patients tended to improve quicker. However, by the end of the trial there was no statistically significant difference between the 2 groups. Subset analyses of HAM-D scores associated with anxiety and sleep revealed no statistically significant differences between the 2 treatments though improvement in anxiety scores was marginally greater for those receiving fluoxetine by the end of the trial. Other global assessments by patients and doctors confirmed the changes in HAM-D scores. Statistically significant weight changes occurred between visits 1 and 5. Whereas fluoxetine-treated patients lost weight (p less than 0.05), dothiepin-treated patients gained weight (p = 0.05) over this period. Adverse effects were reported in 27 patients given fluoxetine and 20 dothiepin. Of these, 14 fluoxetine and 7 dothiepin-treated patients withdrew before the end of the trial. The most common adverse effects were nausea, vomiting and diarrhoea in the fluoxetine group and tiredness, drowsiness and diarrhoea in the dothiepin group. There were no haematological or clinical chemistry changes.
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PMID:A double-blind comparative study of fluoxetine and dothiepin in the treatment of depression in general practice. 267 26

A case of hepatitis is reported in a 38-year-old alcoholic woman taking disulfiram to aid in maintaining sobriety. She presented with anorexia, vomiting, fatigue, right upper-quadrant pain, pruritus, darkened urine, and jaundice after about two weeks of disulfiram 500 mg/d. The patient also had been taking enalapril 10 mg/d for one year. Hepatocellular enzymes, total bilirubin, and eosinophils were significantly elevated. Hepatitis B core antibody, hepatitis A antibody, hepatitis B surface antibody, and antinuclear antibody were negative. After discontinuation of disulfiram, the clinical and biochemical manifestations of hepatitis began to resolve and the patient was discharged in a much improved condition. Seventeen previous cases of disulfiram-induced hepatitis are reviewed. It has been suggested that the mechanism of hepatotoxicity is an allergic or hypersensitivity reaction. The findings in this case are consistent with the earlier descriptions of hypersensitivity hepatitis, and lend further support to the possibility that disulfiram may cause hepatitis.
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PMID:Disulfiram-induced hepatitis: case report and review of the literature. 268 28

Fifty-two non-resectable and recurrent cancer patients with prior treatment, were entered in this study; 1 esophageal, 33 gastric, 1 duodenal, 4 colorectal, 2 pancreatic, 2 bile duct, and 9 breast cancer. The protocol of this therapy was as follows: On day 1, 500 mg/body cyclophosphamide (CPM) was administered by drip infusion, and on day 2, 200 mg/m2 methotrexate (MTX) was infused intravenously for 30 min; immediately after, 500 mg/body 5-fluorouracil (5-FU) was injected by bolus infusion for 5-10 min. On day 3, 24 hours after MTX administration, leucovorin rescue was added. This combination chemotherapy was repeated every two weeks. As a result, 35 of 52 patients were evaluable and the response rate (CR + PR) was investigated; 2/21 (9.5%) for gastric, 2/7 (28.6%) for breast, and 0% for miscellaneous. As complications for side effect, general fatigue, anorexia, nausea, vomiting and stomatitis were observed symptomatically, and leukopenia and thrombocytopenia were recognized in laboratory data as dose limiting factors.
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PMID:[Combination chemotherapy of CPM-MTX-5-FU in non-resectable and recurrent cancer patients]. 271 79

A total of 66 patients with advanced renal cell cancer received a combination of recombinant interferon alpha-2a (18 times 10(6) units subcutaneously 3 times weekly) and vinblastine (0.1 mg. per kg. intravenously every 3 weeks). Four patients were ineligible and 6 were inevaluable for response but evaluable for toxicity. There were no complete and 9 partial responses among the 56 evaluable patients, for a response rate of 16 per cent. Median duration of response was 26 weeks, with a range of 8 to 50 weeks. Responses were observed predominantly in patients with lung and soft tissue metastases. Patients who had undergone nephrectomy did not show a better response rate than those who had not. Almost all patients had a flu-like syndrome, fatigue and anorexia. Other side effects included leukopenia, nausea, vomiting, liver function disturbances and neurotoxicity. Most of the side effects were World Health Organization grade 1 or 2; no grade 4 toxicity was observed. Antibodies against interferon developed in 6 patients during the course of treatment. However, there was no relationship between the appearance of antibodies and disease progression. The combination of recombinant interferon alpha-2a and vinblastine has modest but definite activity in patients with advanced renal cell carcinoma, although the role of vinblastine is unclear.
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PMID:Phase II study of recombinant interferon alpha-2a and vinblastine in advanced renal cell carcinoma. 274 39


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