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 mononucleosis-like illness is frequently recognized retrospectively as the first manifestation of infection with human immunodeficiency virus-type 1 (HIV-1). This acute but transient retroviral syndrome may include symptoms such as malaise, fever, sweats, myalgia, arthralgia, maculopapular rash, diarrhea, and lymphocytic meningitis. We observed two intravenous drug users who developed a severe, febrile illness with subsequent oral thrush (one also had biopsy-proven esophageal candidiasis). Both patients had weight loss, arthralgia, myalgia, and fatigue. These symptoms occurred two weeks after needle-sharing and persisted for 7 weeks in one patient and 10 weeks in the other. Both patients had serologic evidence for both acute HIV-1 and cytomegalovirus infection. Cytomegalovirus enhances HIV-1 replication in vitro, presumably by stimulating HIV-1 gene expression. Thus, the observed syndrome suggests that this viral interaction may be clinically significant because it appears to cause severe additional morbidity, which is not typical for primary infection with HIV-1. After 6 months of follow-up, one patient is completely asymptomatic but shows markedly reduced CD4+ lymphocytes. The other patient developed persistent lymphadenopathy after the acute illness, but is feeling well 21 months after infection.
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PMID:Co-infection with human immunodeficiency virus-type 1 (HIV-1) and cytomegalovirus in two intravenous drug users. 215 58

The safety and tolerability of lisinopril (1.25-160 mg daily) were assessed in 3,270 patients (2,688 hypertensives and 582 patients with congestive heart failure (CHF] and 280 healthy subjects. The duration of therapy ranged from a single dose to 43 months; 438 patients received lisinopril for at least 12 months (mean 20 months). In the hypertensive population, the most frequent adverse events reported were headache, dizziness, cough, nausea, diarrhoea and fatigue, although not all of these events were thought to be related to lisinopril; 6.1% discontinued lisinopril due to adverse clinical events, most commonly cough and nausea. Twelve hypertensive patients died (0.45%), but most of these were not receiving lisinopril at the time of death and none was considered to be drug-related. In CHF patients, the most frequently reported adverse events were dizziness, dyspnoea, diarrhoea, hypotension and fatigue. Again, not all of these reports were considered to be drug-related. Therapy was withdrawn in 9.6% of patients--hypotension, dizziness, diarrhoea and rash being the most frequent reasons. Fifty-three CHF patients died (9.1%) and in three cases death was considered to be related to lisinopril therapy. Hypotension, orthostatic effects or dizziness following the initial dose of lisinopril occurred infrequently (in 1.3% of the hypertensive group, including those receiving hydrochlorothiazide, and in 4.8% of CHF patients). Changes in laboratory parameters were generally minor and seldom resulted in discontinuation of therapy. Long-term treatment of hypertension and CHF with lisinopril for at least 3 years confirms that the drug is well tolerated. Overall, the side-effect profile is very similar to that of other ACE inhibitors with regard to class-specific effects. However, taste disturbance was rarely observed.
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PMID:Clinical experience with lisinopril. Observations on safety and tolerability. 255 Jun 41

In a randomised, placebo-controlled, double-blind study, 822 obese patients of both sexes were given either dexfenfluramine (dF), 15 mg twice daily (404), or placebo (418) in addition to a calorie-restricted diet for 1 year. Patients in both groups lost weight significantly in the first 6 months; after 6 months dF patients had a higher cumulative mean weight loss. Dropout rates were lower in dF patients than in placebo patients, mainly because of dissatisfaction with weight loss in the latter group. More than twice as many dF patients as placebo patients achieved a given weight loss; but more dF patients than placebo patients had transient side-effects (tiredness, diarrhoea, dry mouth, polyuria, and drowsiness).
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PMID:International trial of long-term dexfenfluramine in obesity. 257 57

In September and October of 1987, the California Department of Health Services responded to community complaints by investigating the relationship between health symptoms and community exposure to cotton defoliants. Symptoms experienced during the 1987 cotton defoliation season by 232 residents of cotton-growing communities were compared with symptoms of 175 residents of non-cotton-growing agricultural communities. Fatigue, eye irritation, rhinitis, throat irritation, nausea, and diarrhea were statistically elevated in rates adjusted for age, sex, and race and were reported 60-100% more frequently by respondents living or working near sprayed cotton fields than by the comparison group. These symptom rate elevations were substantially unchanged even after adjustment by a model of potentially confounding factors that included cigarette smoking, chronic illness, and some additional demographic variables.
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PMID:Acute health effects of community exposure to cotton defoliants. 261 May 23

Dilevalol is a new antihypertensive agent that is both a vasodilator, through its beta 2-agonist action, and a nonselective beta antagonist. Two multicenter, double-blind studies were performed: study 1 compared dilevalol administered once-daily with either dilevalol or propranolol every 12 hours; study 2 compared dilevalol administered once daily with placebo. Both studies had a placebo run-in period to establish that the baseline supine diastolic blood pressures were consistent in the mild to moderate severity range (95 to 115 mm Hg) at 2 consecutive visits for study 1 and in the mild severity range (95 to 105 mm Hg) in study 2. Patients then were randomized to the double-blind titration phase, during which doses were titrated over a 9-week period to achieve a supine diastolic blood pressure of less than 90 mm Hg and a decrease from baseline of greater than or equal to 10 mm Hg. Patients were then maintained on a fixed dose for 2 months (study 1) or for 1 month (study 2). Dilevalol given once daily was as effective in reducing supine diastolic blood pressure as dilevalol every 12 hours and propranolol every 12 hours (study 1) and was superior to placebo (p less than 0.001) (study 2). In both studies, dilevalol given once daily was effective and well tolerated. The side-effect profile of dilevalol was similar to that of placebo and different from that of propranolol. Treatment with dilevalol resulted in significantly less fatigue (p less than 0.05), bradycardia (less than 50 beats/minute) and mental depression than with propranolol, but significantly (p less than 0.05) more diarrhea/loose stools.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dilevalol compared with propranolol and placebo for systemic hypertension. 265 29

Organophosphorus and carbamate insecticides are used commonly in agriculture to control pests of crops and animals. These compounds are toxic and livestock poisoning has occurred from mistaken addition of unused insecticide to feeds and animal access to improperly disposed of materials or "empty" containers. The morbidity rate approximates a third of animals exposed and about half of those affected die. Organophosphorus and carbamate insecticides generate their toxic effects by bonding to and inhibiting ChE enzymes (most importantly, AChE), which are responsible for breaking down the neurotransmitter ACh. The accumulation of ACh results in uninhibited impulse transmission at the cholinergic endings, including autonomic preganglionic junctions, certain neurons in the central nervous system, and motor nerves to the skeletal muscles. This eventually leads to fatigue of end organs; death usually is a result of respiratory failure. The "delayed neuropathy syndrome" is caused by some OP insecticides, but the pathophysiology of this syndrome does not involve the inhibition of ChE and accumulation of neurotransmitter. Over 100 anticholinesterase insecticides are in use. Variations in toxicity exist among these compounds, but larger diversities exist in the likelihood of poisoning because of differences in formulations, solvents, and conditions of use. Young animals usually are more sensitive than adults. Some of these agents are among the most toxic of manmade chemicals. These insecticides generally do not accumulate in tissues. The "chronic" effects depend on accrued physiological changes from frequent exposure to nonlethal doses. Clinical signs occur within minutes to a few hours and include the muscarinic signs of salivation, excessive lacrimation, frequent urination, and diarrhea. Concurrent nicotinic effects include muscular tremors followed by weakness and paralysis. Topical exposure results in similar poisoning but the onset of clinical signs may be delayed. Certain pour-on insecticides may cause a delayed (more than a week) syndrome in some breeds. Diagnosis of OP or carbamate insecticide poisoning is made by (1) interpretation of clinical signs and history that are consistent with this poisoning, (2) detection of the chemical compound in stomach or rumen contents and tissues, and (3) demonstration of the adverse biological effect, ChE inhibition.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Organophosphorus and carbamate insecticide poisoning in large animals. 266 12

International study of the effect of dexfenfluramine in obesity (ISIS): 6 months results. ISIS is a multicentre therapeutic trial of the "intention to treat" type organized to test the effectiveness and side-effects of dexfenfluramine combined with diet in the treatment of obesity. This was a randomized, double-blind drug versus placebo study programmed for a one-year period. Eight hundred and twenty-two obese patients were included. Dexfenfluramine was administered in doses of 15 mg b.d. The intermediate results after 6 months of treatment are presented. Significant differences were observed between the dexfenfluramine group (n = 404) and the placebo group (n = 418). In the treated group: 1) the drug withdrawal rate was lower, mainly due to a greater number of patients in the placebo group dissatisfied with their weight loss; 2) about twice as many patients achieved an important loss of weight in terms of percentage of the initial weight or overweight; 3) the cumulative loss of weight was greater; 4) there was a higher incidence of transient side-effects, such as fatigue, diarrhoea, dry mouth, polyuria and drowsiness. These results suggest that dexfenfluramine will be suitable for a more prolonged treatment of obese patients, in addition to diet.
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PMID:[International study of the effect of dexfenfluramine in obesity (ISIS): 6 months' results]. 266 89

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

Twenty-four evaluable patients with metastatic melanoma have been entered in a multicentre Phase II study of two induction cycles of human recombinant interleukin-2 (rIL-2) 18 x 10(6) IU/m2/day continuous i.v. bolus on days 1-5 and days 12-17. Dacarbazine (DTIC) 850 mg/m2 i.v. bolus was given on day 26. The cycle was repeated at five weeks. Maintenance therapy was scheduled three weeks after the completion of the induction treatment, consisting of rIL-2 18 x 10(6) IU/m2/day for five days alternating with DTIC 850 mg/m2 i.v., every three weeks, for a total of 18 weeks. Median age was 44 years (range 23-80), and Karnofsky index was 100 (range 80-100). One patient had received prior chemotherapy with hydroxyurea and one patient had prior radiotherapy. Six patients responded (25%): two had complete responses (CR) and four had partial responses (PR). Stable disease (SD) was seen in five patients. Responses occurred in the following sites: liver 2/9 (22%), lung 3/14 (21%), skin 2/11 (18%), and lymph nodes 3/12 (25%). Duration of CR was 11+ and 13 months. PRs lasted 2, 5, 7, and 11+ months. Of note, time to progression in patients with SD was similar to that of responders: 4, 4, 11+, 11+, and 14+ months. Toxicity included fever, skin rash, fatigue, anorexia, and diarrhoea in most patients. Two patients had a weight gain of more than 10%. Hypotension requiring vasoactive agents or interruption of rIL-2 occurred in four patients, creatinine elevations WHO grade 1-2 in seven patients, and bilirubin elevations WHO grade 1-3 in six patients. One patient developed transient ventricular tachycardia. It appears that rIL-2 and DTIC in this schedule is feasible and effective, but not clearly superior to rIL-2 alone.
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PMID:Sequential administration of recombinant human interleukin-2 and dacarbazine in metastatic melanoma. A multicentre phase II study. 269 78

Seventy-four sequential lymph node biopsies from 30 acquired immunodeficiency syndrome (AIDS)/AIDS-related complex (ARC) patients showed temporal histologic progression from explosive follicular hyperplasia (EFH) to mixed follicular hyperplasia/involution (mixed) to follicular involution (FI) to lymphocyte depletion (LD). This histologic progression correlated with symptoms, development of opportunistic infections (OI), and mortality. At initial biopsy, only 50% of the AIDS/ARC patients with EFH/mixed compared to 100% with FI/LD were symptomatic with weight loss, night sweats, diarrhea, fever, or fatigue. 31% of ARC patients with EFH and 63% with FI developed an OI in a median of 69 months and 5 months, respectively; 86% with LD had a concurrent or previous OI. Ninety percent of ARC patients progressing to FI/LD died; 85% of those persisting with EFH/mixed remained alive 18 to 50 months after initial biopsy. AIDS patients with EFH lived twice as long as those with FI/LD. Progressive histology did not correlate with lymphoma. The number of ARC patients developing Kaposi's sarcoma was too small to draw definitive conclusions.
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PMID:Progressive lymph node histology and its prognostic value in patients with acquired immunodeficiency syndrome and AIDS-related complex. 272 79


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