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)

Alpha-interferon has emerged as the most effective agent for the treatment of chronic hepatitis when active replication of virus B, C, or D is present. Exogenous administration of human alpha-interferon, now possible through modern large-scale production methods, is associated with suppression of virus in blood. Amelioration of liver disease occurs in 35% of patients with hepatitis B virus and in 50% with hepatitis C virus with interferon doses of 30 and 10 MU per week, respectively, for 16-26 weeks; after therapy, persistent normalization of serum alanine aminotransferase is observed in 35% and 27%, respectively. Similar results have now also been reported for chronic hepatitis D. Enhanced response rates (greater than 50%) may be obtained by prolonged intermittent interferon therapy. Combination of interferon with another 'antiviral' agent (vidarabine, acyclovir, prednisone) has not increased therapeutic efficacy. Alpha-interferon induces side effects such as fatigue, flu-like syndrome, myalgia, and changes in mood and granulocytes. Patients with decompensated cirrhosis are particularly prone to bacterial infection and disease exacerbation and should receive lower doses. Interferon, when applied skillfully, induces the highly beneficial transition of active viral replication into viral latency, thereby greatly reducing infectivity, symptoms, and activity of the liver disease. Prevention of death from liver failure or hepatocellular carcinoma is to be expected.
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PMID:Treatment of chronic viral hepatitis anno 1990. 212 46

10 patients with locally advanced bronchioloalveolar carcinoma were treated with interferon-alpha as an inhaled aerosol. Initial doses ranged between 1 and 10 MU daily or thrice weekly and were then increased to 20 MU daily. Treatment was continued until disease progression or excessive toxicity occurred, 9 patients were evaluable for toxicity. In 1 case treatment had to be stopped after 2 weeks due to fever, fatigue and progressive dyspnoea. 2 patients developed fever, 1 had malaise, fatigue and loss of appetite and 2 had dose-dependent transient dyspnoea. According to standard criteria no tumour responses could be detected. In 6 out of 8 evaluated for response to interferon, radiological stabilisation of disease for 7-43 weeks (median 15) was observed. These results point to the feasibility of aerosol inhalation of interferon-alpha, but also to its limited antitumour activity in locally advanced bronchioloalveolar carcinoma.
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PMID:Aerosol application of interferon-alpha in the treatment of bronchioloalveolar carcinoma. 216 95

In a randomized study of advanced renal cell carcinoma 60 patients were allocated to treatment with either recombinant interferon alpha-2a or medroxyprogesterone acetate. Correlation between the dose of interferon alpha-2a and plasma-concentration indicated linear kinetics. Survival was similar in the two treatment groups. Only one complete and one partial response were seen in the interferon group and only one complete response in the medroxyprogesterone group, indicating a low therapeutic potential of both interferon and medroxyprogesterone. Interferon influenced the serum liver enzyme levels; increased transaminases were seen in 17 patients treated with interferon but in only four patients in the medroxyprogesterone group. Two patients had very high serum liver-enzyme levels concomitant with intolerable tiredness, in both patients the symptoms disappeared and the enzymes normalized after discontinuation of the interferon treatment. Antibodies to interferon developed frequently in patients receiving high dose oligomeric interferon therapy but rarely in patients receiving low dose monomeric interferon treatment.
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PMID:Recombinant leukocyte interferon alpha-2a and medroxyprogesterone in advanced renal cell carcinoma. A randomized trial. 218 3

Three clinical observations relating to viral infections are well-known but poorly understood. These are: the susceptibility of people with atopic eczema to viral infections; the occasional precipitation of an atopic syndrome by viral infections; the occurrence of a fatigue syndrome following viral infections. A unifying hypothesis is presented which explains these observations in terms of the interactions between viral infections and essential fatty acid (EFA) metabolism. Key elements of the hypothesis are the facts that interferon requires 6-desaturated EFAs in order to exert its anti-viral effects, that people with atopic eczema have low levels of 6-desaturated EFAs, and that viruses, as part of their attack strategy, may reduce the ability of cells to make 6-desaturated EFAs. The hypothesis has practical implications for the treatment of patients with viral infections.
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PMID:Post-viral fatigue syndrome, viral infections in atopic eczema, and essential fatty acids. 220 89

Interferon, which is produced during viral infections, has cognitive and neurological effects in humans. A dose of 1600 U/g of mouse interferon-alpha significantly depressed horizontal activity, head pokes into a food chamber, and food intake in mice 10 hr and 24 hr after injection. An 800 U/g dose had only slight effects on horizontal activity and food intake, whereas a 400 U/g dose had no effect. There was no evidence of sensitization to interferon when a second 400 U/g dose was given after the 1600 U/g dose. The results imply that mouse interferon-alpha can be used in mice as a model for studying the fatigue and anorexia produced by interferon.
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PMID:An animal model for the behavioral effects of interferon. 220 31

Twenty-six patients were treated in this phase I study with the combination of interleukin-2 (IL2) administered as a continuous infusion and interferon alfa-2a (IFN alpha-2a) administered intramuscularly to patients in an outpatient setting. The maximum-tolerated dose of both agents given as outpatient therapy was 2 x 10(6) U/m2 days 1 to 5 of IL2 and 9 x 10(6) U/m2 days 1, 3, and 5 of IFN alpha-2a for 4 consecutive weeks. A 2- to 4-week rest period was permitted after each 4 weeks of treatment. Fatigue was the treatment-limiting toxicity, and serious clinical or laboratory abnormalities occurred infrequently during this study. Patients with colon cancer metastatic to the liver tolerated treatment worse than patients with other tumors. Twelve of the 15 patients with renal cell cancer were assessable for response determinations. Of these 12 patients, three exhibited complete tumor regression, three have had partial objective regression, and three patients experienced stabilization of rapidly progressive disease. This therapy appears to be well tolerated in an outpatient treatment setting and shows significant activity against advanced renal cell cancer.
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PMID:Phase I study of interleukin-2 and interferon alfa-2a as outpatient therapy for patients with advanced malignancy. 221 2

A 53-year-old woman was admitted to our hospital on Nov. 16, 1987, because of general fatigue. On admission, she had hepatosplenomegaly and her peripheral blood profile showed a white blood cell count (WBC) of 309 x 10(3)/microliters with immature neutrophils, a hemoglobin level (Hb) of 7.6 g/dl, platelet count (PLT) of 536 x 10(3)/microliters, neutrophilic alkaline phosphatase (NAP) score of 44. Both Vitamin B12 and LDH levels were high. The bone marrow showed marked myeloid hyperplasia. In a cytogenetic study, Ph1 was found in 3 of 8 metaphases and Ph1 with an additional abnormality of 8 trisomy was noted in 5 of 8 metaphases. She was diagnosed as having chronic myelogenous leukemia (CML) and treated by i.m. injection of interferon (IFN)-alpha at a daily dose of 6 x 10(6) U. Administration of IFN-alpha induced fever for a few days. WBC, PLT count and LDH level gradually decreased, and the NAP score and hepatosplenomegaly improved. She achieved remission in February, 1988. Administration of IFN-alpha was stopped in April, 1988, when the bone marrow showed hypocellularity and normal karyotype. She was treated with 20 mg of prednisolone daily from May until August, because of progressive pancytopenia. She had received no treatment until July, 1989. In May, 1989, the bone marrow again showed myeloid hyperplasia and Ph1 was found in all cells analyzed. Therefore, we resumed IFN-alpha treatment. It is interesting that remission of CML continues for more than one year after discontinuation of IFN-alpha in this case.
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PMID:[One-year remission of chronic myelogenous leukemia (CML) after discontinuation of interferon-alpha]. 221 81

We conducted a prospective, randomized trial to study the efficacy and tolerance of long-term versus short-term treatment with recombinant interferon alfa-2a in patients with chronic hepatitis B. Ten patients were randomly assigned to a 6-month interferon regimen, and 10 patients were assigned to a 3-week interferon trial. Eleven patients (five assigned to long-term treatment and six to short-term treatment) did not complete interferon therapy: eight had either severe thrombocytopenia or neutropenia; one had pronounced fatigue in relationship to administration of interferon; one had spontaneous bacterial peritonitis and sepsis and died; and one had a massive fatal variceal hemorrhage during interferon therapy. Most of the serious hematologic complications occurred in patients with cirrhosis and hypersplenism. In one patient, seroconversion to hepatitis B virus DNA negativity occurred before the onset of treatment. Four of the five patients able to complete the 6-month interferon regimen and only one of four patients able to complete the 3-week trial had seroconversion to hepatitis B virus DNA negativity. Thus, we conclude that the therapeutic response was better among patients who were able to complete a 6-month interferon trial. In patients with cirrhosis and hypersplenism, development of either severe thrombocytopenia or leukopenia associated with interferon therapy precluded completion of treatment.
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PMID:Long-term versus short-term treatment with recombinant interferon alfa-2a in patients with chronic hepatitis B: a prospective, randomized treatment trial. 221 80

A 68-year-old man with multiple pulmonary metastases from a right renal cell carcinoma was treated with alpha interferon, but there was no improvement. For this reason, alpha interferon was ceased, and daily monotherapy with recombinant interleukin-2 (1,000,000 units/day) was commenced. After 4 months, plain chest x-ray and chest CT revealed complete clearance of the pulmonary metastases. There were no side effects except general fatigue and slight fever. Immunological studies revealed elevation of the leukocyte count (lymphocytes, eosinophils) and enhancement natural killer activity. At 10 months after discontinuation of the drug, recurrence has not been observed. Our case indicates the potential value of interleukin-2 following treatment with alpha interferon.
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PMID:Complete resolution of multiple pulmonary metastases of renal cell carcinoma following intravenous drip infusion of r-interleukin 2: a case report. 223 95

Ninety-seven evaluable patients with measurable, advanced, malignant melanoma were treated with recombinant alpha interferon in a cooperative phase II efficacy trial, whose primary objective was to estimate the response rate. Interferon (rIFN alpha-2a, Roferon-A) was injected subcutaneously daily for 70 days. Dose was escalated in four steps from three million units to 36 million units over ten days. Eight patients responded objectively and six patients (6%) had a complete response. The median duration of complete response was 11 months. Patients achieving complete response had only cutaneous, nodal, or pulmonary disease; some had extensive prior therapy; some could tolerate no more than three million units per day. Few patients could tolerate the target dose of 36 million units daily for 70 days. Limiting toxicity was primarily fatigue. Interferon in tolerable doses is effective in a small subset of patients with melanoma. Comparison of published trials of dacarbazine and recombinant alpha interferon indicates the two drugs have similar activity.
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PMID:Phase II study of recombinant alpha-interferon in malignant melanoma. 223 1


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