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)

Losartan is a novel orally active nonpeptidal antihypertensive agent that specifically blocks the angiotensin II type 1 receptor. This paper compares the short- and long-term safety and tolerability of losartan with those of placebo. Approximately 3800 patients with mild-to-severe essential hypertension were enrolled in 16 double-masked and 4 open clinical trials worldwide. Of these, approximately 2900 were treated with losartan either alone or in combination with other antihypertensive drugs. These trials included patients with diabetes mellitus (n = 133). An additional 5 trials enrolled hypertensive patients with compromised renal function (n = 115) or heart failure (n = 220). Losartan dosages primarily ranged from 10 to 150 mg once daily, with most patients receiving 50 to 100 mg per day. Hypertension trials generally lasted 12 weeks. The most frequently reported adverse events were headache, upper respiratory tract infection, dizziness, and asthenia/fatigue, but only dizziness occurred more frequently (> or = 1%) in the losartan-treated groups. Cough occurred in 3.1% of patients treated with losartan and 2.6% of patients treated with placebo. The overall incidence of clinical and laboratory adverse events in the losartan- and placebo-treated groups was similar among patients with hypertension and either diabetes mellitus, renal impairment, or heart failure. The data suggest that losartan can be safely administered in hypertensive patients with concomitant illnesses. It can be considered for first-line therapy and is suitable as an alternative therapy in patients already experiencing side effects with other agents.
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PMID:Clinical safety and tolerability of losartan. 937 6

Obesity is associated with an increased incidence of infection, diabetes, and cardiovascular disease, which together account for most obesity-related morbidity and mortality. Decreased expression of leptin or of functional leptin receptors results in hyperphagia, decreased energy expenditure, and obesity. It is unclear, however, whether defective leptin-dependent signal transduction directly promotes any of the conditions that frequently complicate obesity. Abnormalities in tumor necrosis factor alpha expression have been noted in each of the above comorbid conditions, so leptin deficiency could promote these complications if leptin had immunoregulatory activity. Studies of rodents with genetic abnormalities in leptin or leptin receptors revealed obesity-related deficits in macrophage phagocytosis and the expression of proinflammatory cytokines both in vivo and in vitro. Exogenous leptin up-regulated both phagocytosis and the production of proinflammatory cytokines. These results identify an important and novel function for leptin: up-regulation of inflammatory immune responses, which may provide a common pathogenetic mechanism that contributes to several of the major complications of obesity.
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PMID:Leptin regulates proinflammatory immune responses. 943 11

We identified 174 cases of chronic severe renal failure (blood creatinine > 650 mumol/l) and/or blood urea > 35 mmol/l) in a retrospective study of patients admitted to hospital between January 1989 and June 1996. Of these patients, 110 were men and 64 were women. The mean age was 36 +/- 15 years. Fifty three patients had a history of hypertension before admission, 3 patients had diabetes and 3 had gout. The most frequent clinical signs were dyspnea (55.2% of all patients), fatigue (78.2%), vomiting (63.2%) and edema (66.1%). The prevalence of hypertension was 64.9%. Glomerulonephritis was found in 42.5% of patients, chronic interstitial nephritis in 16.1%, polycystic kidney disease in 2 cases, congenital renal hypoplasia in 4 cases and unclassified kidney disease in 14.4% of cases. End-stage renal failure was complicated by heart failure in 40.2% of patients, pericarditis in 31.6%, hemorrhage of the gastrointestinal tract in 15% and infections in 22.4%. 47.7% of the patients died following admission.
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PMID:[Epidemiology of severe chronic renal insufficiency in Burkina Faso]. 950 95

The aim of this randomized controlled trial was to assess the effects of treatment with continuous positive airway pressure versus conservative therapy (CT) on well-being, mood, and functional status in subjects with mild sleep-disordered breathing (SDB). One hundred and eleven subjects, aged 25 to 65 yr, with a respiratory disturbance index (RDI) of 5 to 30 and without subjective pathologic sleepiness, were randomized to nasal CPAP or to CT. Ninety-seven subjects were followed-up after 8 wk. Treatment response was assessed from changes between baseline and follow-up measures of mood, energy/fatigue, and functional status/general health. Of the 51 subjects randomized to CPAP, 25 (49%) experienced an improved outcome, as compared with 12 of 46 of subjects (26%) randomized to CT (p < 0.05). The odds of experiencing a treatment response in the CPAP as compared with the CT group were 2.72 (OR: 1.18 to 6.58, 95% CI). A beneficial effect of CPAP over CT was most evident among individuals without sinus problems and among subjects with hypertension or diabetes. Differential treatment responses were not related to degree of baseline sleepiness or SDB. This suggests that middle-aged snorers with relatively low levels of SDB (RDI < 30) may benefit more from nasal CPAP than from less specific therapy directed at improving breathing during sleep. CPAP therapy may be beneficial to a broader group of subjects than previously appreciated.
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PMID:Improvement of mild sleep-disordered breathing with CPAP compared with conservative therapy. 951 3

Brown adipose tissue (BAT) has the capacity for uncoupled mitochondrial respiration and is proposed to be a key site for regulating energy expenditure in rodents. To better define the role of BAT in energy homeostasis, we previously created a line of transgenic mice with deficiency of BAT (UCP promoter-driven diphtheria toxin A transgenic mice [UCP-DTA]) mice. These mice develop obesity that initially is due to decreased energy expenditure and later accompanied by hyperphagia despite increased levels of circulating leptin. In addition, the obesity of these mice is accompanied by severe insulin-resistant diabetes and hyperlipidemia. To better define the basis for leptin resistance in this model, we treated UCP-DTA mice with leptin (300 microg i.p., b.i.d.) and compared their response with that of leptin-treated ob/ob and FVB control mice (30 microg i.p., b.i.d.). Leptin treatment of FVB and ob/ob mice decreased their body weight and food intake and improved their glucose homeostasis. In contrast, tenfold higher dosages of leptin had no effect on body weight, food intake, or circulating insulin or glucose concentrations of UCP-DTA mice. Hypothalamic neuropeptide Y (NPY) mRNA expression was lower in UCP-DTA mice than in littermate control FVB mice in the fed state, and increased progressively in response to food restriction as leptin levels fell. In parallel to the levels of hypothalamic NPY, corticosterone levels were initially suppressed and rose with food restriction. Thus food intake, body weight, and insulin and glucose homeostasis of UCP-DTA mice are all extraordinarily resistant to leptin, whereas hypothalamic NPY and the hypothalamopituitary adrenal (HPA) axis may remain under leptin control. Further elucidation of the mechanisms underlying leptin resistance in UCP-DTA mice may provide valuable insights into the basis for leptin resistance in human obesity.
Diabetes 1998 Feb
PMID:Severe leptin resistance in brown fat-deficient uncoupling protein promoter-driven diphtheria toxin A mice despite suppression of hypothalamic neuropeptide Y and circulating corticosterone concentrations. 951 18

A 65-year-old man with rapidly progressing small cell lung cancer found in the course of renal failure is reported. The patient had a medical history of hypertension, diabetes mellitus, and cardiovascular disease. Hemodialysis was introduced following renal failure, but pneumonia resulted in a transient exacerbation and his complaint of general fatigue did not improve. Examination for the fatigue revealed no apparent abnormalities. Three months later, he died of small cell lung cancer.
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PMID:A case of rapidly progressing small cell lung cancer incidentally found during the course of renal failure. 956 May 32

A 74 year old patient with diabetes mellitus was hospitalized because of nausea, recurrent vomiting and increasing fatigue. Shortly before admittance the patient had diarrhea. He also reported a recent onset of aversion against meat consumption. Clinical investigation revealed a possible right-sided paraumbilical abdominal tumor, normal bowel sounds, a vascular bruit and a normal white blood count with increased band forms. During hospitalisation the general condition of the patient deteriorated rapidly with fever and increasing numbers of immature granulocytes. The patient finally died under the symptoms of a paralytic ileus with hypotonia and hypoglycemia. Autopsy revealed a fist-sized stenosing tumor in the cecum with the histology of a mainly well differentiated, cylindrocellular adenocarcinoma. As immediate cause of death a bilateral paracentral lung embolism with pulmonary edema was found, the latter probably as immediate consequence of preterminal heart failure.
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PMID:[Intestinal paralysis in long-term diabetes mellitus]. 965 91

We have investigated the potential for the human brain to use lipid fuels during acute hypoglycemia. Nine healthy male subjects underwent hyperinsulinemic (1.5 mU/kg x min) stepped hypoglycemic clamps on two occasions, infusing Intralipid (20%) and heparin (0.1 U/kg x min) on one occasion only (ILH), with an identical study without infusion of ILH acting as a control. Five subjects also underwent euglycemic clamping with Intralipid/heparin infusion. During hypoglycemia, ILH raised circulating levels of nonesterified fatty acids, glycerol, and beta-hydroxybutyrate, although the latter did not rise until after the onset of counterregulation. With ILH, epinephrine responses [area under the curve (AUC), 127.9 +/- 31.7 vs. 175.1 +/- 27.4 nmol/L x 180 min; P = 0.03] and GH responses (AUC, 260 +/- 91 vs. 1009 +/- 150, P < 0.01) were reduced and delayed (glucose thresholds, 2.8 +/- 0.04 vs. 3.0 +/- 0.1 mmol/L; P = 0.04), with a trend toward reduced cortisol responses. Similarly, hypoglycemic symptom scores were diminished during ILH (AUC, 647 +/- 162 vs. 1222 +/- 874; P = 0.03). However, there was no significant effect on the deterioration in four-choice reaction time, one measure of cognitive deterioration [glucose thresholds, 2.6 +/- 0.1 vs. 2.7 +/- 0.1 mmol/L, ILH vs. control (P = 0.75); AUC, 1420 +/- 710 vs. 2250 +/- 1080 ms/min (P = 0.59)]. During euglycemic clamping with Intralipid/heparin infusion studies, there was no rise in hormones, four-choice reaction time, or symptoms other than hunger and tiredness. Both nonesterified fatty acids and glycerol can penetrate the mammalian brain and be metabolized. Raised levels were able to reduce neurohumoral responses to hypoglycemia, but could not protect cognitive function. This suggests that regional differences exist in human brain metabolism between glucose-sensing and cognitive areas of brain, which may be important in the understanding of the mechanisms of glucose sensing and in the genesis of hypoglycemia unawareness in insulin-dependent diabetes.
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PMID:Reduced counterregulation during hypoglycemia with raised circulating nonglucose lipid substrates: evidence for regional differences in metabolic capacity in the human brain? 970 75

After 2 months of streptozotocin-induced diabetes in rats, the membrane potential of the diaphragm muscle when measured in vitro at 30 degrees C was unchanged but the tetanic tension, the half-relaxation time of the isometric twitch and the fatigue resistance were each reduced. Treatment of the diabetic rats with the antihyperglycaemic agent metformin prevented the decrease in half-relaxation time and the greater degree of fatigue in the diaphragms. The possibility that changes in H+ and cyclic AMP concentrations in the diabetic muscles contributed to the decreased contractile function and that metformin acted by attenuating these changes is discussed.
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PMID:The influence of streptozotocin-induced diabetes and the antihyperglycaemic agent metformin on the contractile characteristics and the membrane potential of the rat diaphragm. 971 70

Menorrhagia--menstrual periods lasting longer than 7 days and totaling blood losses greater than 80mL--affects 9%-14% of otherwise healthy women, and it can signal cancer, an endocrinologic disorder, or gynecologic disease. Blood loss can be high enough to result in anemia, fatigue, and syncope. Most often, abnormal uterine bleeding such as menorrhagia involves a disruption in the hypothalamic-pituitary axis, the ovary, and/or the uterus. Other identified causes include medications (especially psychotropics) that cross the blood-brain barrier; chronic diseases such as cancer, diabetes, and liver and kidney dysfunction; endocrine disorders, perimenopausal anovulation, polycystic ovary disease, pituitary tumors, and abnormal estrogen cycling caused by morbid obesity; and anatomic abnormalities of the uterus. Routine tests include hematocrit or hemoglobin to detect and evaluate anemia, thyroid stimulating hormone (TSH) level to evaluate thyroid function as a possible cause, and a pregnancy test to rule out an incomplete, spontaneous abortion as a cause. A Pap test is recommended to screen for dysplasia that can suggest a gynecologic cancer cause. Additional screening for endocrine disorders that may be causing menorrhagia include tests of thyroid, liver, and kidney function, and tests of follicle stimulating hormone (FSH), prolactin, and cortisol levels. Treatment can be medical or surgical. Medical treatment includes prostaglandin inhibitors, specifically nonsteroidal antiinflammatory drugs (NSAIDs), and hormonal therapy with estrogen, progesterone, gonadotropin-releasing hormone agonists, or oral contraceptives such as medroxyprogesterone (Depo-Provera). Surgical treatment includes hysteroscopic endometrial ablation by physical agents, laser electrodiathermy, and "roller ball," or surgical, resection. Hysterectomy is the treatment of last resort.
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PMID:Treatment Decisions in the Management of Menorrhagia. 974 72


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