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-two patients with metastatic malignant melanoma received either 36 X 10(6) U (15 patients) or 18 X 10(6) U (7 patients) of human recombinant interferon alpha-2-A daily for 3 months by the intramuscular route, with progressive increase of dosage. This was followed in responders by a maintenance treatment consisting of 3 intramuscular injections per week in the same doses as those received at the end of the induction treatment. Out of 18 patients assessable for effectiveness, 1 had complete remission (7 months +) and 3 had partial response (52,61 and 82 days respectively), an overall improvement rate of 22%. The main side-effects observed were: pseudoinfluenza syndrome (100%), fatigue (100%), somnolence (95%), anorexia (90%) and haematological disorders. Dosage reduction was necessary in 13 of the 15 patients receiving 36 MU. This study shows that human recombinant interferon alpha-2-A has antitumoral activity in metastatic malignant melanoma. Other studies, notably with therapeutic combinations, are needed to determine the optimal dosage regimen of the drug and to increase its effectiveness.
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PMID:[Human recombinant leukocyte interferon alpha-2-A in 22 cases of metastatic malignant melanoma]. 295 23

A phase I-II study of human recombinant interferon gamma (rIFN-gamma) was conducted in patients with various advanced cancer refractory to standard chemotherapies. In the phase I study, seven patients received 14 courses of escalating doses ranging from 2 X 10(6)U/m2 to 64 X 10(6)U/m2 by 1-hour intravenous infusion for 5 consecutive days. The toxicities were high fever with chills, anorexia, occasional nausea and vomiting, elevation of serum GOT, and dose-related leukopenia and neurotoxic symptoms such as heavy fatigue with somnolence or lethargy, both of which were reversible. The pharmacokinetics showed that the peak levels of serum rIFN-gamma activity were dose-related but decreased rapidly to below measurable levels within 6 hours after infusion in patients receiving less than 12 X 10(6)U/m2. Considering these data, the dosage of rIFN-gamma 6 X 10(6) U/m2 by daily intramuscular injection for more than 4 weeks was selected for the early phase II study. There was no partial response out of 11 evaluable patients but a stable condition was observed in 2 cases of renal cell carcinoma and one case each of breast cancer and ovarian cancer. All toxicities seen were similar to those observed in the phase I study, but no tachyphylaxis developed with continued dosage. The antitumor effect of rIFN-gamma remains to be evaluated in a further study employing higher doses.
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PMID:[Phase I-II study of recombinant interferon gamma]. 298 59

Napoleon would sleep very little. He frequently woke up during night and worked. Brief sleeping time in day repaired his fatigue. He had also a short and thick neck. In the last fourth of his life he progressively suffered from obesity, daily involuntary sleepiness and his intellectual capabilities undoubtedly decreased. Our experience of 48 cases of sleep apnea syndrome diagnosed by mean of polysomnography allow no to think that Napoleon suffered from this disease. Historical consequences of this pathology is discussed.
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PMID:[Did Napoleon suffer from sleep apnea syndrome?]. 304 29

More than 5,000 primary-care physicians enrolled more than 22,000 patients with mild to moderate hypertension in a postmarketing study in which guanfacine hydrochloride, a centrally acting antihypertensive agent, was given for 28 days. The objectives of the evaluation were: (1) to obtain broad experience with guanfacine for the management of essential hypertension in a clinical practice setting; (2) to obtain information on patient acceptance of guanfacine, 1 mg HS, for the control of essential hypertension; and (3) to obtain more information on the drug's safety in clinical practice. Patients had to be at least 21 years of age, to be receiving a thiazide-type diuretic, and to have a sitting diastolic blood pressure of 95 to 114 mmHg. Women who were pregnant or lactating or planning to become pregnant during the evaluation were excluded. Blood pressure and heart rate were measured before guanfacine was started and at the completion of the study. Adverse on-therapy events were reported at the return visit. The average blood pressure in the general patient population decreased by 17/12 mmHg, that is, from 164/100 to 147/88 mmHg in four weeks. The magnitude of the reduction was not significantly influenced by age, race, sex, duration of hypertension, or the use of concomitant antihypertensive therapy. Adding guanfacine to another antihypertensive regimen resulted in mean reductions of 11 to 15 mmHg diastolic pressure, and the substitution of guanfacine for another antihypertensive agent resulted in mean reductions of 10 to 11 mmHg diastolic pressure. The most common side effect reported was dry mouth in 6% of patients, followed by dizziness, somnolence, fatigue, headache, and nausea, each reported in fewer than 3% of patients. More than 80% of the participants continued to receive guanfacine after the study. Of the total patient population, 7% discontinued guanfacine because of lack of efficacy, 10% because of side effects, and 3% for other reasons. The results of this large postmarketing study confirmed the results of controlled clinical trials conducted prior to marketing.
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PMID:A postmarketing evaluation of guanfacine hydrochloride in mild to moderate hypertension. 306 7

A double-blind controlled study comparing the effects of bupropion to doxepin in outpatients with primary depression was conducted to evaluate efficacy and safety differences between the two drugs. Following a 7-day placebo washout period, patients could be treated for up to 13 weeks on either treatment. Antidepressant response was assessed by the Hamilton Depression and Anxiety Scales, Clinical Global Severity and Improvement Ratings, and the Zung Self-Rating Depression Scale. Comparable efficacy between the compounds was found across the 13-week study. Doxepin differed from bupropion mainly on the sleep factor of the Hamilton Depression Scale, with doxepin improving sleep to a greater extent than bupropion. Doxepin produced a greater incidence of anticholinergic side effects, including dry mouth, constipation, sleepiness, and tiredness, in comparison to bupropion. Also, increased appetite and weight gain were consistent side effects of doxepin relative to bupropion.
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PMID:Double-blind comparison of doxepin versus bupropion in outpatients with a major depressive disorder. 308

The psychopharmacological effects of fluvoxamine, 50 mg twice a day, were compared with those of mianserin, 20 mg twice a day, and placebo, each given for 8 days in a double-blind crossover design to 9 healthy human volunteers. At least one week was left between the 8-day courses of drugs. Testing was carried out before and 3 h after taking the morning dose on Days 1 (pre-drug), 4, and 8, and comprised EEG, cognitive and psychomotor tasks, and self-ratings of mood and bodily symptoms. Fluvoxamine had no effect on any of the EEG wavebands, but mianserin increased voltages in the slow wavebands as compared with placebo. This effect was particularly pronounced on Days 4 and 8. Mianserin significantly decreased critical flicker fusion frequency and speed of reaction time, and slowed down tapping rate; digit symbol substitution and symbol copying test performances were also impaired by mianserin. These effects were most marked after the first dose and had lessened somewhat later in the week. Symbol copying was the only task impaired by fluvoxamine as compared with placebo. Mianserin caused drowsiness after the first dose but this effect declined by Day 8. By contrast, fluvoxamine induced feelings of anxiety, sweatiness, trembling, nausea, loss of appetite, restlessness, muscle tension, irritability, tiredness, headache, and dizziness; these effects were most evident in the middle of the week and relatively reduced at the end of the week. Mianserin produced a few of these effects but they tended to be maximal on Day 1 or 4 and then to wear off.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The psychopharmacological effects of repeated doses of fluvoxamine, mianserin and placebo in healthy human subjects. 308 44

Ritanserin is an investigational serotonin-S2 receptor antagonist with activity in a variety of psychiatric disturbances characterized by dysthymia or anxiety. This investigation evaluates acute safety and tolerability of ritanserin in 12 healthy males. Ritanserin 10 mg, 20 mg, and placebo were administered as single doses in a randomized, double-blind, crossover fashion. Treatment effects on vital signs, laboratory tests, a mood evaluation test, electrocardiograms (ECGs), and reported adverse experiences were monitored. Plasma levels were determined at two hours postdose. Results indicated no clinically relevant effects on vital signs, laboratory tests, ECGs, or mood evaluations. Dose proportionality was demonstrated. The incidence of total adverse effects (primarily somnolence and fatigue) after single-dose administration was 25 percent for placebo, 75 percent for 10 mg, and 81.8 percent for 20 mg. There was a relationship between incidence of adverse effects and dose, but no general correlation between plasma levels and severity of adverse experiences. The results indicate that ritanserin is safe and tolerable following acute administration of 10 mg and 20 mg oral doses.
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PMID:Safety evaluation of ritanserin--an investigational serotonin antagonist. 309 82

The efficacy of terfenadine, a nonsedating H1 antihistamine, in the management of chronic idiopathic urticaria was compared with chlorpheniramine and placebo in a parallel multicenter trial. Subjects with symptoms of hives for 3 days per week for at least 6 weeks were initially screened and admitted if no identifiable cause for symptoms could be determined. Patients entered a single-blind placebo period, and if hives of moderate severity were present for at least 3 days during the week, they were randomly assigned in a double-blind fashion to take terfenadine, 60 mg twice daily, chlorpheniramine, 4 mg three times a day, or placebo for 6 weeks. Data were analyzed for 122 patients. Those patients receiving both active treatments noted significant improvement in symptoms: pruritus, redness, number of hives, and waking hours during which hives were present, at the end of the first day of therapy. Symptom control by terfenadine was statistically superior to placebo during all 6 weeks, as rated by both patients and investigators. However, statistical significance was not achieved for chlorpheniramine at all observation points. Diphenhydramine was permitted as a relief medication for refractory symptoms and was taken by 52% of subjects receiving placebo, 26% taking chlorpheniramine, and only 9% of patients who were receiving terfenadine. In addition to providing superior symptom control, terfenadine caused less drowsiness and fatigue than chlorpheniramine. Terfenadine is a useful therapeutic agent for primary management of chronic idiopathic urticaria.
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PMID:Double-blind comparison of terfenadine, chlorpheniramine, and placebo in the treatment of chronic idiopathic urticaria. 312 20

Residency training may disrupt normal sleep/wake cycles, resulting in mood and performance deficits and alterations in biological rhythms. To characterize such disturbances and determine whether they are associated with an alteration in the day/night pattern of melatonin excretion, measurements were obtained around-the-clock in seven male subjects, each studied in two 48-h sessions. Session 1 was conducted during the week before beginning a residency, and session 2 at 6 months into a first-year surgical residency. The mean time of the end of nocturnal sleep and the timing of the temperature rhythm were both (P less than .01) approximately 2.3 h earlier in session 2 (vs. 1). The sleepiness rhythm and the overall mood score rhythm were also phase-advanced (P less than .05) in session 2. The mean value of mood around-the-clock was significantly worse due to increased anger, tension, confusion, depression, and fatigue in session 2. Vigilance, tested by simple reaction time, did not exhibit a 25-h rhythm and was worse in session 2 with an increase (P less than .05) in mean response latency less than 1 s and an increase (P less than .01) in lapse time (microsleep, greater than 1- s latency). The urinary cortisol rhythm exhibited a raised curve average value (mesor) in session 2 (vs. 1, P less than .05), but no difference was revealed in amplitude or acrophase. Urinary excretion of Na+, K+, and Cl- did not differ between sessions, though the Na+/K+ ratio peaked earlier in session 2 (P less than .05). The urinary 6-sulfatoxymelatonin rhythm did not differ in timing, amplitude, or mesor between sessions. A residency training schedule can be associated with altered timing in rhythms of sleep, sleepiness, temperature, and mood and with deterioration of mood and performance without detectable alteration of the endogenous melatonin pattern as exhibited by the excretion rate of the principal urinary metabolite.
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PMID:Alterations of temperature, sleepiness, mood, and performance in residents are not associated with changes in sulfatoxymelatonin excretion. 322 34

The efficacy and safety of propranolol in the treatment of anxiety was compared with those of chlordiazepoxide and placebo in a 3-week, double-blind study of 212 patients. After a 1-week, single-blind placebo-washout period, patients were randomized to receive either propranolol (80, 160, or 320 mg/day), chlordiazepoxide (30, 45, or 75 mg/day), or placebo. Patients were evaluated by three physician-rated scales--Hamilton Rating Scale for Anxiety (HAM-A), Covi Anxiety Scale (CAS), and Clinical Global Impressions scale--and two patient-rated scales--Symptoms Checklist 90 and Profile of Mood States. Patients in all groups demonstrated significant improvement in their level of anxiety at all time points compared with their baseline level. At Week 1 propranolol and chlordiazepoxide patients were significantly better than placebo patients, as measured by the HAM-A and CAS. At Week 2 only propranolol was superior to placebo, based on HAM-A and CAS scores. Fifteen patients prematurely terminated because of adverse reactions (4 taking propranolol, 4 taking placebo, and 7 taking chlordiazepoxide). The incidence of side effects was similar for the two active drugs; fatigue, drowsiness, and change in libido were significantly more frequent with chlordiazepoxide and drowsiness and indigestion were more frequent with propranolol compared with placebo.
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PMID:Comparative efficacy of propranolol, chlordiazepoxide, and placebo in the treatment of anxiety: a double-blind trial. 330 88


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