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)

A Phase I study of recombinant interferon-gamma (rIFN-gamma) was conducted to determine the toxicity and pharmacokinetics of this lymphokine in acquired immunodeficiency syndrome (AIDS) patients with Kaposi's sarcoma (KS). Sixteen patients with AIDS/KS were entered into a fixed-dose trial at either 0.001, 0.01, 0.1, or 1.0 mg/m2 of rIFN-gamma. rIFN-gamma was initially administered either as a single 24-hr continuous iv infusion or as a single im injection, followed 4 days later by a 10-day course of daily therapy by the same route. Following a 1-week washout period, this sequence of administration was then repeated, with the drug given by the alternate route. Pharmacokinetic analysis of the 1.0-mg/m2 group revealed that peak serum levels of up to 153 U/ml occurred 2-4 hr after im injection and that steady-state levels of up to 40 U/ml were reached approximately 7-12 hr after beginning iv infusion. Dose-related toxicities in this trial included fever, headache, fatigue, nausea, and hepatitis, all of which were most severe at the two highest doses. Dose-dependent depression of the total white blood-cell (WBC) count, affecting both granulocytes and lymphocytes, was the most common laboratory abnormality. Natural killer (NK)-cell activity was slightly enhanced at a dose of 0.1 mg/m2 but suppressed at 1.0 mg/m2 of drug; monocyte-mediated cytotoxicity, in contrast, was significantly increased only at the highest dose. No dose-related changes were noted in KS lesions, HLA-DR expression by peripheral blood mononuclear cells, lymphocyte blastogenesis, or the ability to culture cytomegalovirus (CMV) from body fluids. We conclude that a maximally tolerated dose (MTD) for this drug is in the range of 0.1-1.0 mg/m2 and that at least modest evidence of systemic immunomodulation may be seen when rIFN-gamma is given at doses at or near this MTD.
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PMID:A phase I trial of recombinant human interferon-gamma in patients with Kaposi's sarcoma and the acquired immunodeficiency syndrome (AIDS). 254 86

A cluster of 134 patients who had undergone Epstein-Barr virus (EBV) serological testing because of suspected chronic EBV syndrome was investigated in Nevada. Fifteen case-patients were identified who had severe, persistent fatigue of undetermined etiology for more than two months. When compared with the remaining 119 patients who had less severe illnesses and with 30 age-, sex-, and race-matched control-persons, these 15 patients had significantly higher antibody titers against various components of EBV and against cytomegalovirus and herpes simplex and measles viruses. Epstein-Barr virus serology could not reliably differentiate individual case-patients from the others, and the reproducibility of the tests within and among laboratories was poor. As a group, the case-patients appear to have had a syndrome that is characterized by chronic fatigue, fever, sore throat, and lymphadenopathy. The relationship of this fatigue syndrome to EBV is unclear; further studies are needed to determine its etiology.
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PMID:A cluster of patients with a chronic mononucleosis-like syndrome. Is Epstein-Barr virus the cause? 303 37

Eleven patients of Chinese origin experienced spontaneous reactivation of chronic active hepatitis B. Eight HBsAg-positive patients were followed for an average of 15 months prior to, while three others presented during reactivation. Fatigue, hepatomegaly and jaundice were frequent findings. Elevation of both serum ALT (average = 1,212 units per liter) and hepatitis B virus DNA levels were noted in all patients, and reactivation lasted an average of 4.4 months. During resolution, clinical symptoms abated, serum ALT levels reverted toward normal, and in nine patients, the hepatitis B virus DNA values became undetectable. All patients lacked evidence for acute hepatitis A, Epstein-Barr Virus, cytomegalovirus or hepatitis delta virus infection. Histologic findings of liver tissue from eight patients showed piecemeal necrosis and fibrosis. Within the parenchyma, varying degrees of hepatocytolysis with cuffing, perivenular necrosis and acidophilic bodies were noted. Ground-glass cells and regenerative changes also were observed. Cirrhosis was not present in any of the liver biopsies. These findings suggest that spontaneous reactivation of hepatitis B occurs in heterosexual patients with chronic active hepatitis B and contributes to chronic inflammation and to the progression of their liver disease.
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PMID:Spontaneous reactivation of hepatitis B in Chinese patients with HBsAg-positive chronic active hepatitis. 361 49

We present data on 14 patients with chronic symptoms of disabling fatigue in association with serologic evidence of active Epstein-Barr virus (EBV) infection. Two thirds were women, and the average age at onset was 29.6 years. Forty-three percent were known to have had previous infectious mononucleosis, but the usual criteria for that diagnosis were not helpful with the present syndrome. Eighty-six percent had serologic evidence of cytomegalovirus (CMV) infection. Profound immunodeficiency was not present, but 71% had partial hypogammaglobulinemia, and minor abnormalities of T cell subsets were noted in six of seven patients studied. Fifty-seven percent achieved temporary serologic and symptomatic remission after an average duration of 33 months. Only one patient has a sustained remission. Comparison is made with other reported chronic, recurrent, and persistent EBV syndromes, and tentative diagnostic criteria for chronic mononucleosis syndrome are presented. Recently available EBV serologic techniques allow for identification of patients who have reactivated EBV infection, and this reactivation may be related to symptoms.
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PMID:Chronic mononucleosis syndrome. 609 68

A 17-year-old girl was admitted to our hospital because of drowsiness, diplopia and gait difficulty. She had been well until ten days before admission when fever, drowsiness, headache and general fatigue developed. On admission, there were drowsiness, ophthalmoplegia, ataxia and hyporeflexia. CSF cells and anti-CMV antibody titers increased. CMV-DNA was detected in the CSF by the polymerase chain reaction (PCR). Serum anti-GQ1b antibody was positive. During recovery, forced laughing temporarily appeared. The neurological symptoms disappeared completely. CSF anti-CMV antibody titers became normalized and CSF CMV-DNA-PCR became negative. This is the first case report of Bickerstaff's brainstem encephalitis associated with CMV infection.
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PMID:[Bickerstaff's brainstem encephalitis associated with cytomegalovirus infection]. 802 40

In the treatment of cytomegalovirus (CMV) disease in patients with AIDS, a life-long suppression therapy following an induction therapy consisting of ganciclovir or foscarnet is essential. Due to drug-related toxicities, anti-CMV therapy frequently has to be discontinued. To determine whether toxicities and side effects may be reduced with an alternating combination therapy consisting of ganciclovir and foscarnet (ganciclovir: 5 mg/kg every other day; foscarnet: 120 mg/kg every other day), 10 AIDS patients with CMV disease received this maintenance therapy for a median time of 18.5 weeks (5-51 weeks). Side effects were reported from 5 patients (nausea 5, malaise/fatigue 2, penile ulcers 1). Hematological or renal toxicities were mild, 1-week discontinuation of therapy due to neutropenia was necessary in 1 patient. Progression of CMV disease was observed in 3 patients at 2, 6, and 30 weeks of maintenance therapy. Median relapse-free interval for all patients was 105 days. We conclude that combination therapy with ganciclovir and foscarnet can be used safely for induction and maintenance therapy. Therefore, this regimen should be assessed in further trials to evaluate safety, efficacy, and the development of resistance in comparison to ganciclovir or foscarnet monotherapy.
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PMID:Safety of alternating ganciclovir and foscarnet maintenance therapy in human immunodeficiency virus (HIV)-related cytomegalovirus infections. An open-labeled pilot study. 819 Dec 40

Patients with chronic fatigue as a major complaint frequently present with recurrent sore throat, and on physical examination they have hyperemia and lymphoid hyperplasia of the pharyngeal area. Pharyngeal scrapings were obtained from 41 such patients and analyzed for Epstein-Barr virus or cytomegalovirus DNA by colorimetric in situ hybridization. Results were compared with healthy control subjects matched for age and sex. Epstein-Barr virus-DNA was detected more frequently in male patients, 5/9 (55.6%), than controls, 0/6 (0%), but there was no difference in frequency in female patients, 4/32 (12.5%), than control subjects, 1/29 (3.4%). Cytomegalovirus-DNA was detected infrequently in patients and controls, 13% versus 22% respectively. The presence of EBV-DNA did not correlate with antibody titers nor with the complaint of sore throat. Four of the five males who had positive EBV-DNA in the pharyngeal smears have now recovered.
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PMID:Detection of Epstein-Barr virus and cytomegalovirus in patients with chronic fatigue. 839 63

The number of AIDS patients over age 60 has risen steadily in the past decade. The number of transfusion-acquired AIDS cases probably has peaked--or will soon peak. Homosexual (or bisexual) behavior remains the predominant risk factor for AIDS until the seventh decade. Disease progression appears to be more rapid in the elderly, although the observed shorter survival time may result from a delay in diagnosis. Symptoms of HIV infection are often nonspecific, such as fatigue, anorexia, weight loss, and decreased physical and cognitive function. The five most common opportunistic infections in older HIV-infected patients are Pneumocystis carinii pneumonia, tuberculosis, Mycobacterium avium complex, herpes zoster, and cytomegalovirus. A number of features of HIV-related dementia may help to distinguish it from Alzheimer's disease.
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PMID:HIV infection in older patients: when to suspect the unexpected. 850 Jul 75

In order to determine the prevalence of cortisol deficiency in advanced HIV disease and to examine whether it may be predicted by clinical features or biochemical abnormalities, we conducted a prospective study which assessed responses to a rapid ACTH stimulation test (short-duration synthetic corticotrophin test, synacthen test) in HIV-positive patients with a CD4 count of < or = 50 x 10(6)/l. Subjective fatigue, postural drop in blood pressure, electrolyte changes, presence of concurrent opportunist infection and drug treatment were recorded. Cortisol responses were defined as 'normal' (a post stimulation cortisol level > or = 450 nmol/l), 'abnormal' (post stimulation cortisol level < 350 nmol/l) or 'impaired' (an intermediate response). Of 49 patients tested (42 male, seven female), a suboptimal response (abnormal or impaired) was found in 14 (29%) and frank insufficiency in eight (16%). Cortisol deficiency was not predicted by postural drop in blood pressure, biochemistry or symptoms of fatigue. Patients with an impaired/abnormal test were not more likely to have cytomegalovirus or mycobacterial disease but were more likely to be taking megestrol acetate (P = 0.05, Fisher's exact test). Two of three patients with initially normal tests developed impaired/abnormal cortisol responses on re-testing 6-9 months later. Cortisol deficiency is common in late stage HIV disease, but symptoms of fatigue and postural hypotension, as well as biochemical findings, are poor predictors of cortisol deficiency. We found good subjective response to therapy. Routine screening by a rapid ACTH stimulation test is recommended in HIV-positive patients with CD4 count < or = 50 x 10(6)/l. Re-testing at regular intervals may be necessary. The interaction between megestrol acetate, cortisol metabolism and synacthen testing requires further investigation.
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PMID:Prevalence of cortisol deficiency in late HIV disease. 852 25

In the immunocompromised patients and during foetal life an acute infection due to the cytomegalovirus (CMV) causes great morbidity. In adults without predisposing factors the acute infection with CMV is rarely symptomatic, but can also provoke fever, fatigue, headache and anorexia for weeks. The peripheral blood smear shows big atypical lymphocytes within a relative lymphocytosis. The suspicion of the CMV infection is confirmed by the serological evidence of IgM anti-CMV antibodies. There is no etiological treatment, the evolution is spontaneously favorable most of the time. Establishing the diagnosis is reassuring for the patient and for the physician and avoids unnecessary analyses and treatments. We describe a series of 11 adults without predisposing factors who contracted an acute cytomegalovirus infection.
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PMID:[Clinical presentation of primary cytomegalovirus infection in a non-immunodepressed adult]. 869 75


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