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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Relatively little is known about the combined effects of hypercapnia and fatigue on the human diaphragm. We examined the effects of acute hypercapnia and fatigue in seven subjects by measuring changes in transdiaphragmatic pressure (Pdi) elicited by cervical magnetic stimulation after 2 min maximal voluntary ventilation (MVV) while breathing air and also with the inspired PCO(2) increased to 8% for 12 min before and during the MVV. Diaphragm strength was assessed before and at 0, 20, 40, 60, and 90 min after the MVV in both studies with the subjects breathing air. There was no difference in the level of ventilation for each run. Mean (+/- SD) twitch Pdi (TwPdi) fell significantly (p < 0.01) at 20 min after the control and hypercapnic MVV; (30.4 [7.8] to 27.0 [8.1] cm H(2)O control and 30.3 [4.1] to 27.3 [5.0] cm H(2)O CO(2)) and remained significantly (p < 0.01) below baseline. The changes in TwPdi at 20 to 90 min were not significantly different between the control and CO(2) runs. The decrease in TwPdi at 0 min after MVV, however, was greater (15%) in the hypercapnic run than in the control run (8.1%) (p < 0.05) when compared with baseline valves. Hypercapnia does not intensify long lasting fatigue but may reduce diaphragm contractility immediately after MVV.
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PMID:Effect of hypercapnia on maximal voluntary ventilation and diaphragm fatigue in normal humans. 1055 22

If chronic hypercapnia in patients with severe COPD occurs as a consequence of respiratory muscle (RM) weakness or fatigue, we would expect that ventilatory muscle recruitment (VMR) and exercise performance in stable hypercapnic patients would differ from those in eucapnic patients. We evaluated exercise performance and RM function at rest and during exercise in 19 eucapnic (PCO(2) 40 +/- 3 mm Hg), and 13 hypercapnic (PCO(2) 52 +/- 10 mm Hg) patients with severe COPD. A metabolic cart was used to determine V E, V O(2), V CO(2), and HR. Gastric (Pg) and esophageal (Ppl) balloons were used to measure Pg, Ppl, and Pdi. Ventilatory muscle recruitment pattern (VMR) was partitioned using end-inspiratory and end-expiratory Pg and Ppl. Hypercapnic patients had lower FEV(1) (0.60 +/- 0.24 versus 0.95 +/- 0.31 L, p < 0.001), MVV (28 +/- 11 versus 41 +/- 13 L, p < 0.001), resting PO(2) (61 +/- 11 versus 70 +/- 11 mm Hg, p < 0.001), peak PO(2) (60 +/- 20 versus 75 +/- 22 mm Hg, p < 0.005), and V E(max) (24 +/- 10 versus 32 +/- 12 L/min, p < 0.001). Patients in both groups had similar FRC (5.7 +/- 1.6 versus 5.0 +/- 1.5 L), V O(2)max (0.58 +/- 0.30 versus 0.76 +/- 0.32 L/min), Watts (45 +/- 48 versus 71 +/- 59), V E/MVV (88 +/- 33 versus 79 +/- 14), and HRmax (117 +/- 17 versus 128 +/- 18 beats/min). PI(max) (67 +/- 28 versus 65 +/- 32 cm H(2)O) and PE(max) (98 +/- 34 versus 96 +/- 40 cm H(2)O) were also similar in both groups. VMR (DeltaPg/DeltaPpl) at rest (-0.28 +/- 0.51 versus 0 +/- 0.35) and during exercise (0.4 +/- 0.2 versus 0.39 +/- 0.15) was equally affected in both groups. We conclude that exercise capacity and ventilatory muscle recruitment are similarly impaired in eucapnic and hypercapnic patients with severe COPD. These findings make inability of the lung to increase ventilation and not respiratory muscle dysfunction a more attractive explanation for CO(2) retention in stable hypercapnic patients.
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PMID:Respiratory muscle recruitment and exercise performance in eucapnic and hypercapnic severe chronic obstructive pulmonary disease. 1071 37

This study aimed to investigate tissue hypoxia on the cellular level in sepsis. Eighteen pigs weighing 18-27 kg were studied. Intramucosal-arterial PCO(2) gradient (PCO(2)-gap) and intramucosal pH (pH(i)) were calculated using tonometry. A blind loop of the small intestine was constructed for repeated tissue biopsies to measure intestinal energy-related metabolites and lactate concentration. Six animals served as controls. In 12 animals, faecal peritonitis was induced. Six of these animals were studied without further interventions, while the others were resuscitated with dextran to maintain cardiac index at baseline level. Untreated peritonitis caused an increase in PCO(2)-gap and a drop in pH(i). The intestinal energy metabolism was not disturbed until the end of the experimental period, with a decreased energy charge value and a moderately increased lactate concentration. In peritonitis-dextran animals, PCO(2)-gap and pH(i) remained at baseline level and the energy metabolism was not disturbed. We conclude that in peritonitis, PCO(2)-gap - like pH(i) - can be influenced by other factors than strictly anaerobic tissue metabolism.
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PMID:Intramucosal pH and pCO(2) do not strictly correlate with intestinal energy metabolism in experimental peritonitis. 1087 60

A collection of 12 papers published between 1957 and 1972 are revisited. The papers had a common theme of the use of rebreathing carbon dioxide and explored a variety of topics in respiratory physiology. The first study established a method for the noninvasive and indirect estimation of arterial carbon dioxide pressure that was suitable for the routine clinical monitoring of respiratory failure and whose clinical utility remains to this day, but which also provided observations that were the stimulus for the studies that followed. The rate of rise in the partial pressure of carbon dioxide (PCO(2)) during rebreathing led to an analysis of body carbon dioxide storage capacity. Knowledge of carbon dioxide storage led to a method for quantifying lactate production in exercise without the need for blood sampling. The changes in ventilation that accompanied the increase in PCO(2) provided the basis for a rapid method for measuring aspects of breathing control (Read's method), which was later modified to measure the ventilatory response to hypoxia. The physiology of breath-holding was explored through observations of the fall in breath-holding time as PCO(2) climbed. Rebreathing also allowed increases in voluntary ventilation to be achieved without the development of alkalosis, leading to studies of maximal voluntary ventilation and respiratory muscle fatigue. Equilibration of PCO(2) during rebreathing was used to measure mixed venous PCO(2) during exercise and develop an integrated approach to the physiology of exercise in health and disease; alveolar-arterial disequilibrium in PCO(2) during exercise was uncovered. Equilibration of PCO(2), as well as PO(2), during rebreathing of carbon dioxide and nitrogen gas mixtures showed different time courses of venous gases at the onset of exercise. Starting with the rebreathing of carbon dioxide in oxygen mixtures in a small rubber bag, an astonishing range of topics in respiratory physiology was explored, with observations that remain valid, but in some respects unresolved, to the present day.
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PMID:Multum in parvo: explorations with a small bag of carbon dioxide. 1152 Nov 43

Both preponderance as well as underweight normally starts in childhood and puberty and hurt the fate of young women mostly a life long. Weight and fat tissue as an energy storage regulates through the hormone Leptin appetite, food intake and therefore the energy reserves. With this hormone exist a common pathophysiological regulation unit, which causes in case of preponderance an increased, in case of underweight a decreased cyclus activity. Besides short term influences (like the development of the PCO-syndrome and/or fatigue fractures) the long-term consequences especially the accumulation of the visceral fat, the cardio-vascular diseases, metabolic syndrome, type-II-diabetes, mammary- and endometrial carcinoma play a special role. On the other hand chronic underweight very frequently leads through chronic estrogen defect to osteopenia, osteoporosis and therefore to cyclus disturbances, sterility and osteoporosis. A simple finding like weight, has thus an important predictive quality for later illnesses and their prevention.
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PMID:[The overweight and underweight girl: from findings to prevention]. 1207 Jul 92

The ability of insulin to stimulate glucose disposal varies more than six-fold in apparently healthy individuals. The one third of the population that is most insulin resistant is at greatly increased risk to develop cardiovascular disease (CVD), type 2 diabetes, hypertension, stroke, nonalcoholic fatty liver disease, polycystic ovary disease, and certain forms of cancer. Between 25-35% of the variability in insulin action is related to being overweight. The importance of the adverse effects of excess adiposity is apparent in light of the evidence that more than half of the adult population in the United States is classified as being overweight/obese, as defined by a body mass index greater than 25.0 kg/m(2). The current epidemic of overweight/obesity is most-likely related to a combination of increased caloric intake and decreased energy expenditure. In either instance, the fact that CVD risk is increased as individuals gain weight emphasizes the gravity of the health care dilemma posed by the explosive increase in the prevalence of overweight/obesity in the population at large. Given the enormity of the problem, it is necessary to differentiate between the CVD risk related to obesity per se, as distinct from the fact that the prevalence of insulin resistance and compensatory hyperinsulinemia are increased in overweight/obese individuals. Although the majority of individuals in the general population that can be considered insulin resistant are also overweight/obese, not all overweight/obese persons are insulin resistant. Furthermore, the cluster of abnormalities associated with insulin resistance - namely, glucose intolerance, hyperinsulinemia, dyslipidemia, and elevated plasma C-reactive protein concentrations -- is limited to the subset of overweight/obese individuals that are also insulin resistant. Of greater clinical relevance is the fact that significant improvement in these metabolic abnormalities following weight loss is seen only in the subset of overweight/obese individuals that are also insulin resistant. In view of the large number of overweight/obese subjects at potential risk to be insulin resistant/hyperinsulinemic (and at increased CVD risk), and the difficulty in achieving weight loss, it seems essential to identify those overweight/obese individuals who are also insulin resistant and will benefit the most from weight loss, then target this population for the most-intensive efforts to bring about weight loss.
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PMID:Obesity, insulin resistance, and cardiovascular disease. 1474 3

Non-alcoholic steatohepatitis (NASH) is one of the most common liver disorders. This is highly prevalent in obese and diabetic subjects. Persons with central obesity are at particular risk. Other clinical predictors are age more than 40-50 years and hyperlipidemias, but none of these factors is invariable for causation of NASH. Other reported associations are, celiac disease, Wilson's Disease and few other metabolic diseases. Drugs, particularly amiodarone, tamoxifen, nucleoside analogues and methotrxate have also been linked to NASH. The disease is evenly distributed in both sexes but advanced disease is more common in women. Ethnic variation exists and African Americans are less affected than Hispanic Americans. Specific clinical features of NASH are infrequent. Patients usually come to clinical attention by elevated liver enzymes found on routine evaluation but on history, about two third of patients will admit to have mild fatigue and about half will report right upper quadrant pain. Rarely, patient may present with a complication of cirrhosis. Physical examination may reveal hepatomegaly and splenomegaly. Research in last few years has stressed that development of steatosis, stetohepatitis, fibrosis with subsequent cirrhosis are most probably the result of insulin resistance. Therefore, clinical features may reflect existence of insulin resistance. Obesity, particularly central obesity is most important of these. Patients may have sleep apnea syndrome. Hypertension and manifestations of diabetes mellitus like polyuria, polydypsia, and neurological deficits may occur. Patients may have varying combination of obesity, diabetes, hyperlipidemia, hypertension and impaired fibrinolysis (syndrome X). Children with insulin resistance may show acanthosis nigricance. Patients with polycystic ovary syndrome, which consists of insulin resistance, diabetes, obesity, hirsutism, oligo or polymenorrha and hyperlipidemia may have NASH. Other rare manifestations of insulin resistance, which can be seen in patients of NASH are lipomatosis, lipoatrophy/lipodystrophy and panniculitis. Most other rare conditions known to cause NASH like peroxisomal diseases, mitochondialpathies, Weber-Christian disease, Mauriac syndrome, Madelung's lipomatosis and abetaliopprotenemia also have insulin resistance. This is believed that primary defect underlying insulin resistance is impairment in postreceptor pathways (through tyrosine kinase activity) of insulin action. Primary defect in insulin receptors appear uncommon. This results in down regulation of insulin receptor substance 1 (IRS-1) signaling by excess free fatty acids. In muscle, activated IRS-1 promotes translocation of glucose transporter protein 4 (GLUT4) to cell membrane. As a result, monocyte glucose uptake by GLUT4 increases glucose disposal from blood and reduced need for insulin. PKC-0 is a likely candidate as serine kinase in muscle regulated by fatty acids that can impair the activation of IRS-1. Insulin resistance is usually evaluated by fasting insulin levels, Quantitative Insulin Check Index (QUICKI) and Homeostasis Model Assessment of Insulin Resistance (HOMA), C-peptid/insulin ratio oral glucose tolerance test and hyper insulinemic euglycemic clamp. The clamp technique is considered the gold standard.
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PMID:Insulin resistance and clinical aspects of non-alcoholic steatohepatitis (NASH). 1619 20

Premenopausal women with polycystic ovary syndrome (PCOS) are at a much higher risk for excessive daytime sleepiness, fatigue, and insulin resistance than control women. Elevated levels of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) are presumably part of the pathogenesis of these clinical manifestations. Forty-two obese women with PCOS, 17 body mass index-comparable obese controls, and 15 normal-weight controls free from apnea participated in the study that included one 8-hour nighttime polysomnography, single morning cytokine plasma concentrations, and insulin resistance indices. Women with PCOS exhibited higher plasma concentrations of IL-6 than obese controls, who had intermediate values, or normal-weight controls, who had the lowest values (4.75 +/- 0.5 vs 3.65 +/- 0.4 vs 1.84 +/- 0.3 pg/mL, P < .01). Tumor necrosis factor alpha values were higher in PCOS and obese controls compared with normal-weight controls, but the difference was not statistically significant (4.05 +/- 0.3 vs 3.79 +/- 0.2 vs 3.14 +/- 0.2 pg/mL, P = .103). Based on backward regression analysis, IL-6 levels had a stronger association with the PCOS group than with the obese group, and the sleep or hypoxia variables did not make a significant contribution to either IL-6 or TNF-alpha. Both IL-6 and TNF-alpha correlated positively with body mass index (P < .01) in obese controls but not in women with PCOS. Furthermore, within the PCOS group, IL-6 and TNF-alpha correlated more strongly with indices of insulin resistance than obesity. We conclude that IL-6 levels are elevated in obese women with PCOS independently of obesity or sleep apnea and may represent a pathophysiologic link to insulin resistance.
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PMID:Plasma interleukin 6 levels are elevated in polycystic ovary syndrome independently of obesity or sleep apnea. 1683 44

Obesity has epidemic proportions in Western societies and, because of its significant association with morbidity and mortality, is a major public health issue. Excessive daytime sleepiness (EDS) and fatigue (tiredness without increased sleep propensity)--which have been associated with obesity--have a significant impact on individual well-being and public safety. In this article, we review data that challenge the belief that sleep apnea and sleep disruption per se are the primary determinants of obesity-related daytime sleepiness and fatigue. Specifically, it appears that obesity per se is associated with objective and subjective daytime sleepiness compared to normal-weight controls regardless of sleep apnea and sleep loss. Indeed, obese patients without sleep apnea are sleepier compared to nonobese controls whereas within the morbidly obese, those who have high sleep efficiency at night are sleepier than those who have low sleep efficiency. In addition, in recent studies based on large random samples of the general population, the primary determinants of subjective EDS were depression and metabolic disturbances, that is, obesity/diabetes, and not sleep apnea or objective sleep disruption. Furthermore, sleepiness and fatigue are very prevalent in conditions associated with insulin resistance, for instance, the polycystic ovary syndrome (PCOS), independently of sleep apnea or obesity, or in conditions of insufficient physical activity. On the basis of these data, we propose that obesity-related objective daytime sleepiness and fatigue are associated primarily with metabolic and psychological factors and less with sleep apnea and sleep disruption per se. Furthermore, we suggest that objective sleepiness is primarily related to metabolic factors, whereas fatigue appears to be related to psychological distress. Finally, based on data from studies in normal controls and patients with sleep disorders, we propose that the interaction of the hypothalamic-pituitary-adrenal (HPA) axis and proinflammatory cytokines determines the level of sleep/arousal within the 24-h cycle, that is, "hypercortisolemia" plus hypercytokinemia is associated with low sleep efficiency and fatigue, whereas "eucortisolemia" or "hypocortisolemia" plus hypercytokinemia is associated with high sleep efficiency and objective sleepiness.
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PMID:Obesity-related sleepiness and fatigue: the role of the stress system and cytokines. 1714 48


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