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 interferons at doses of 3-9 MU subcutaneously, three to seven times/week, have been administered to 32 patients with malignant endocrine pancreatic tumors. The objective biochemical response rate was 63 percent with a median duration of 20.5 months. Significant reduction of tumor size was only noticed in 20 percent of the patients. Alpha interferon administered to 111 patients with malignant carcinoid tumors showed objective biochemical responses in 42 percent of the patients with a median duration of 32 months. Another 39 percent of the patients showed stabilization of disease without any further tumor growth. Subjective improvement was noticed in 70 percent of the patients. When survival data are analyzed in patients with malignant carcinoid tumors, the median survival from start of treatment was 80+ months in the group of patients treated with alpha interferon, which should be compared with only eight months in a historical group treated with chemotherapy (streptozotocin plus 5-fluorouracil). The adverse reactions to alpha-interferon treatment are dose-dependent and include, mainly, flu-like symptoms, fatigue, and low-grade weight loss. Autoimmune reactions are noted in about 20 percent of the patients. Patients treated with recombinant alpha interferons might develop neutralizing interferon antibodies (6-27 percent), which abrogate the anti-tumor response. The anti-tumor effect in neuroendocrine tumors includes anti-proliferation, apoptosis, differentiations, and cytotoxic/cytostatic effects. Furthermore, immunomodulation is obtained by increased expression of class I antigens on tumor cells. Four patients also developed antibodies directed against carcinoid tumor cells. Alpha interferons induce several nuclear enzymes such as 2'-5'-A synthetase, p-68 kinase, and Mx-A proteins, which are involved in a downregulation of expression of growth factors, oncogenes, and peptide hormones, leading to anti-proliferation and/or apoptosis. The response to alpha-interferon treatment might be predicted by analysis of the induction of 2'-5'-A synthetase in samples from neuroendocrine tumors. Stimulatory tests of hormone secretion, such as meal stimulation of pancreatic polypeptide secretion or secretin test, clearly demonstrate a normalization during alpha-interferon treatment, which might depend on reduced peptide production and/or secretion but also on eradication of malignant cell clones. In summary, alpha interferons have demonstrated significant anti-tumor effects in patients with malignant neuroendocrine gut and pancreatic tumors. The adverse reactions are dose-dependent and manageable. The anti-tumor effects of alpha interferons are pleiotropic and include several direct effects on tumor cells but also immunomodulation.
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PMID:Interferons in the management of neuroendocrine tumors and their possible mechanism of action. 134 65

A total of 178 patients with metastatic renal cell cancer were randomized to receive interferon alfa-2a (rIFN alfa-2a) or interferon alfa-2a+vinblastine (VLB). IFN alfa-2a was injected intramuscularly at a dose of 18 MIU 3 times a week and VLB was given intravenously at a dose of 0.1 mg/kg once every 3 weeks. The response rate was 11% for patients on monotherapy and 24% for those on combination treatment. The 5-year survival for 145 eligible patients was 9%, independently from the treatment arm. The performance status was significantly related to long-term prognosis, and 13% of the patients with performance status 0 were alive at 5 years, as compared to 6% and 0% for patients with a WHO grade of 1 and 2, respectively. The most frequent adverse events in both treatment arms were flu-like symptoms (95%), fatigue (70%) and gastrointestinal disturbances (68%). Leukopenia was observed more frequently with combination treatment (53%) than with IFN alfa-2a alone (30%). In conclusion, rIFN alfa-2a monotherapy at this dose and schedule has modest antitumor activity in metastatic renal cell cancer. The combination of rIFN alfa-2a+VLB results in a doubling of the response rate, but this does not translate into prolonged survival. Toxicity (except leukopenia) and tolerance were similar in both treatment arms.
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PMID:Recombinant interferon alfa-2a with or without vinblastine in metastatic renal cell carcinoma: results of a European multi-center phase III study. 139 Mar 5

Abrupt or gradual discontinuation of tricyclic antidepressants may precipitate withdrawal symptoms. The most common of these are general somatic or gastrointestinal distress, anxiety and agitation, sleep disturbance, akathisia, parkinsonism, paradoxical behavioral activation and mania. There are very few reports of withdrawal reactions following discontinuation of clomipramine since it has not been in use in the US until recently. 2 patients with withdrawal symptoms following discontinuation of clomipramine are presented. A 45-year-old man had general somatic symptoms, including headache, myalgia, weakness, fatigue (flu-like syndrome) and nervousness and insomnia after clomipramine, 75 mg/d, had been discontinued abruptly. All symptoms disappeared without treatment after 3 days. A 47-year-old woman presented mainly with severe insomnia, anxiety, agitation, jitteriness and tension after discontinuing a low dose of 25 mg/d of clomipramine. Symptoms disappeared after she started self-treatment with 50 mg/d of the drug. It is important to differentiate withdrawal symptoms from relapse of the primary psychiatric disorder.
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PMID:[Withdrawal reactions after clomipramine]. 145 99

A severe foodborne outbreak of group A streptococcal disease (T28) affected 122/169 people (72%) who attended a church party or ate leftovers from the party. The median incubation time was 42 h. Muscular pain or weakness and fatigue usually preceded pharyngeal symptoms. Complications included otitis media with perforation, peritonsillitis requiring tonsillectomy, arthritis and pericarditis. A 45-year-old man died 36 h after he developed an influenza-like illness, and at necropsy there were histological signs of early streptococcal septicaemia. The strain produced erythrogenic exotoxins B and C. Streptococci were probably transmitted by sliced eggs on sandwiches. Laboratory experiments showed that there was an increment in viable count of streptococci with 6 logs after incubation in egg yolk for 24 h at room temperature. The unusually warm climate and flaws in food handling routines contributed to this large foodborne epidemic.
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PMID:A foodborne outbreak of group A streptococcal disease at a birthday party. 146 75

We initiated a program to evaluate patient reasons for refusing immunization in an allergy clinic. A general medicine clinic was studied for comparison. For the Northwestern University Allergy Service (NUAS) there were five full-time salaried and seven voluntary physicians. In the general medicine clinic there was one part-time salaried physician. Four hundred eighty-eight NUAS patients and 48 general medicine patients were evaluated. Ninety-five percent of the patients agreed to vaccination. Egg allergy, the only valid contraindication to influenza vaccination, was reported by three (< 1%) patients. Transient mild symptoms consisting of fatigue, myalgias, rhinitis and/or diarrhea were reported in 20% of the patients who received vaccination. No severe systemic reactions were reported. No significant difference in the vaccination acceptance rate was noted between the subspecialty and primary care outpatient clinics. The importance of influenza immunization in patients with asthma and in other high-risk populations deserves emphasis, and high success rates are achievable when emphasized by physicians.
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PMID:Influenza vaccination: a successful outpatient program. 149 Jun 24

We conducted a phase I trial of fluorouracil (5-FU), leucovorin, (LCV), and recombinant interferon-alpha-2b (rIFN-alpha-2b). The doses of each of the three agents were escalated sequentially. 5-FU and LCV were administered by IV bolus, weekly for 6 weeks and rIFN-alpha-2b was administered by subcutaneous injection, three times weekly for 6 weeks. Twenty-nine patients with advanced cancer (75% colon or pancreatic cancer) were treated. Partial remissions were observed in three patients (10%) with previously untreated colon cancer, colon cancer refractory to 5-FU plus LCV and previously untreated pancreatic cancer, respectively. An additional three patients with pancreatic, prostate, and rectal cancer had a 50% reduction in tumor markers but no change in objective tumor measurements. The toxicity of this regimen was tolerable. The most common toxicities were diarrhea, fatigue, flu-like symptoms, nausea/vomiting, and mucositis. However, no fatal or life-threatening toxicities were observed. We conclude that the combination of 5-FU, LCV, and rIFN-alpha-2b can be safely administered and recommend further evaluation of this regimen in patients with tumors of gastrointestinal origin using doses of 5-FU 600 mg/m2, LCV 500 mg/m2, and rIFN-alpha-2b 10 x 10(6) U.
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PMID:A phase I trial of fluorouracil, leucovorin, and recombinant interferon alpha-2b in patients with advanced malignancy. 155 45

Infections caused by Chlamydia pneumoniae were first described in 1985. The infection can cause common cold, sore throat, hoarseness, cough, headache, fatigue and sometimes influenza-like illness. Examination can indicate serous otitis media, sinusitis, laryngitis, bronchitis and pneumonia. The course can be long and relapsing. The recommended drugs for treatment are tetracycline or erythromycin for at least two weeks. Five verified cases are described in the article, four of them with symptoms from the upper respiratory tract only. It is concluded that Chlamydia pneumoniae is a not unusual cause of upper airway diseases. Up to now the diagnosis can best be verified by micro immunofluorescence. The authors call for a rapid and reliable test for use in physician's office. It is proposed that infections caused by Chlamydia pneumoniae be termed TWAR.
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PMID:[TWAR infection is a common diagnosis in outpatient clinics]. 157 35

The chronic fatigue syndrome (CFS) is a poorly understood condition with nonspecific signs and symptoms, especially debilitating fatigue. Most patients can pinpoint the onset of their illness and usually describe a flu-like state. The search for an etiologic agent has focused on a number of viruses such as Epstein-Barr, enteroviruses, retroviruses, and human herpesvirus-6. Evidence supports persistent viral infection in a small percentage of CFS patients. Immunologic abnormalities do exist in CFS, which indicate the presence of immune activation in CFS patients. Although abnormal muscle biopsies have been found in some patients with CFS, strength and endurance appear normal, but perception of exertion may be abnormal. Patients with chronic fatigue have a high incidence of premorbid and concurrent psychiatric disorders, and on physical examination many often have reproducible tender points similar to fibromyalgic patients. Clinical evaluation should rule out other potential causes of fatigue, but elaborate diagnostic tests are seldom required. Presently, no specific treatment exists for CFS. A cognitive behavioral approach with or without the use of tricyclics has been advocated. Patients should be encouraged to maintain functional status and should not be discouraged from exercise. Several medications have been tried but with no definite clinical benefit.
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PMID:Chronic fatigue syndrome. 161 43

Recombinant Interleukin 4 was administered by subcutaneous injection at daily doses of 0.5, 1.0 or 5.0 micrograms kg-1 to nine patients as part of a Phase I Dose Toxicity Study. Dose limiting toxicity was reached at 5 micrograms kg-1 day-1. Symptoms of toxicity included fatigue, 'flu like symptoms and elevated liver enzymes. Modest but significant elevations of neutrophil and platelet counts occurred. No clear evidence of antitumour effects emerged although pain in metastatic lymph nodes and a small fall in myeloma paraprotein levels during dosing were observed. In vitro and murine in vivo studies indicate that patients with lymphoproliferative disease should be selected for Phase II trials.
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PMID:Recombinant human interleukin 4 (IL-4) given as daily subcutaneous injections--a phase I dose toxicity trial. 163 69

To clarify the role of Epstein-Barr virus (EBV) infection and the value of EBV antibody testing in evaluating patients with chronic fatigue, we studied 200 consecutive patients with chronic fatigue (mean duration, 9 years). Complete EBV serologic panels were obtained for 154 patients, 35 (23%) of whom met serologic or clinical criteria for chronic or reactivated EBV infection. We compared these patients with chronic EBV infection (CEBV cases) to 35 age- and sex-matched patients who were selected from the same cohort of fatigued patients but who did not meet the criteria (CEBV control subjects). We found few differences between groups in demographic characteristics, clinical features, and symptoms; CEBV cases were more likely to meet criteria for the proposed chronic fatigue syndrome (14% vs 0%), and to report that they suffered from an influenza-like illness at the onset of their fatigue syndrome (34% vs 12%), that they lost their job because of their fatigue (37% vs 11%), and that their fatigue was improved by recreational activity (26% vs 3%). Physical examination and laboratory testing showed few abnormalities in either group. Psychiatric morbidity was common in both groups, including mood disorders (63% of CEBV cases vs 54% of CEBV controls), anxiety (11% vs 9%) and somatization disorder (9% in each group). We conclude that EBV serologic patterns have little clinical usefulness in evaluating patients with chronic fatigue.
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PMID:Antibodies to Epstein-Barr virus in patients with chronic fatigue. 164 95


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