Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cachexia is a complication of many disorders. It is associated with an extremely poor prognosis and many symptoms. The wasting process affects particularly skeletal muscle causing extreme fatigue and weakness. In many underlying conditions associated with cachexia, the patient also suffers an often unexplained severe dyspnoea along with weakness, asthenia and exhaustion. There appears to be marked similarities in the cause of dyspnoea and fatigue between different cachectic conditions. Using the example of cardiac cachexia, this article reviews the evidence linking skeletal muscle reflex inputs to ventilatory control and exaggerated chemoreflex responses as candidates for the heightened perception of dyspnoea which cannot be explained by heart or lung dysfunction in many patients. Evidence is reviewed that similar processes may occur in other cachexias, especially those complicating cancer, AIDS, chronic liver disease, and chronic lung disease. Potential novel therapeutic strategies to combat these cachexia symptoms are reviewed.
 ...
PMID:Origin of symptoms in patients with cachexia with special reference to weakness and shortness of breath. 1216 18

Fatigue is an extraordinarily common consequence of cancer and its treatment. Fatigue can result in diminished cognitive and physical functional capacity and may be the result of multiple causes. However, aside from psychological factors, the main physiological factors leading to fatigue in cancer patients are anemia, severe deconditioning, and muscle wasting that is secondary to cachexia. One of the most common measures of functional capacity is maximal aerobic capacity, also called VO2max. VO2max is a measurement of the maximal capacity of the entire cardiorespiratory system and muscles to consume oxygen. It is strongly predictive of functional status, and it is strongly related to circulating hemoglobin. Research has indicated that the use of recombinant human erythropoietin to treat anemia can preserve or increase VO2max. In addition, aerobic exercise training has been demonstrated to greatly relieve symptoms of fatigue in patients with cancer. It is both safe and effective in this patient population. Muscle wasting results in diminished protein reserve and extreme muscle weakness. Progressive resistance exercise training has been demonstrated to greatly increase strength, improve protein balance, and increase muscle mass even in very frail and old men and women. It should be strongly encouraged in patients experiencing muscle wasting and weakness. A comprehensive "cancer rehabilitation"program is described, which is made up of (1) correcting anemia related to cancer or its treatment; (2) aerobic conditioning to improve VO2max; and (3) progressive resistance exercise in patients experiencing muscle weakness or wasting. In this way, the physiological causes of fatigue may be addressed and quality of life improved.
 ...
PMID:Physical function in men and women with cancer. Effects of anemia and conditioning. 1238 Sep 60

Fatigue and impaired physical performance are common and sometimes serious problems of cancer patients during and after treatment. To avoid fatigue, cancer patients are often advised to rest and downregulate their daily activities. However, these recommendations can cause paradoxical results. Since inactivity induces muscular wasting, prolonged rest can result in further loss of endurance. Recent studies suggest that exercise, as well as behavioral and some psychosocial interventions, may reduce fatigue and improve the performance status of cancer patients. In this paper, we review interventions proposed for the treatment of cancer-related fatigue and present the results of a study about the effects of exercise on the physical performance of patients with hematological malignancies. Sixty-six inpatients (34 men, 32 women) undergoing conventional ( n=45) or high-dose chemotherapy with stem cell rescue ( n=21) for the treatment of a hematological malignancy exercised daily on a treadmill. Physical performance was assessed on admission and once a week during hospitalization (30+/-10 days, range 10-49). Physical performance remained unchanged in a submaximal standard stress test (on admission: 5.5+/-1.4 km/h; midhospitalization: 5.3+/-1.3 km/h; at discharge: 5.5+/-1.3 km/h; p=0.60) despite chemotherapy and its related complications. A significant decrease in the mean hemoglobin concentration (from 10.3+/-2.0 g/dl on admission to 9.6+/-1.2 g/dl at discharge; p=0.03). We conclude that a daily endurance-training program reduces the treatment-related loss of physical performance in patients with hematological malignancies undergoing chemotherapy.
 ...
PMID:Effects of endurance training on the physical performance of patients with hematological malignancies during chemotherapy. 1294 60

Chronic heart failure (CHF) remains an important and increasing public health care problem. It is a complex syndrome affecting many body systems. Body wasting (i.e., cardiac cachexia) has long been recognised as a serious complication of CHF. Cardiac cachexia is associated with poor prognosis, independently of functional disease severity, age, and measures of exercise capacity and cardiac function. Patients with cardiac cachexia suffer from a general loss of fat tissue, lean tissue, and bone tissue. Cachectic CHF patients are weaker and fatigue earlier, which is due to both reduced skeletal muscle mass and impaired muscle quality. The pathophysiologic alterations leading to cardiac cachexia remain unclear, but there is increasing evidence that metabolic, neurohormonal and immune abnormalities may play an important role. Cachectic CHF patients show raised plasma levels of epinephrine, norepinephrine, and cortisol, and they show high plasma renin activity and increased plasma aldosterone level. Several studies have also shown that cardiac cachexia is linked to raised plasma levels of tumour necrosis factor alpha and other inflammatory cytokines. The degree of body wasting is strongly correlated with neurohormonal and immune abnormalities. The available evidence suggests that cardiac cachexia is a multifactorial neuroendocrine and metabolic disorder with a poor prognosis. A complex imbalance of different body systems may cause the development of body wasting.
 ...
PMID:Cardiac cachexia. 1551 2

beta-Endorphin and a C-terminal analogue have been shown to decrease muscle fatigue and increase glucose uptake in muscles of normal mice. In order to provide evidence whether these peptides might be useful in muscle-wasting conditions and whether the two actions of the peptides are interdependent, the effect of beta-endorphin on muscle fatigue and glucose uptake was studied using isolated hemidiaphragm preparations of dystrophic mice as well as normal mice. Muscle contractions were elicited by high-frequency stimulation of the phrenic nerve. Glucose uptake was measured using (nonmetabolizable) 2-deoxy-D-[1-(3)H]glucose. beta-Endorphin and the C-terminal analogue reduced fatigue in normal muscles of males but not females. Insulin had no effect in either sex. The peptides increased 2-deoxyglucose uptake in contracting and noncontracting muscles of normal males and females. beta-Endorphin reduced fatigue and increased deoxyglucose uptake in dystrophic muscles. The effect on fatigue was not due to increased glucose uptake, as the energy substrate present was pyruvate. Nerve stimulation released beta-endorphin immunoreactivity from intramuscular nerves of dystrophic mice. It is hypothesized that beta-endorphin released from motor nerves as well as from the pituitary could be responsible for improving muscle function during exercise. beta-Endorphin or analogues could have therapeutic use in muscle-wasting disease.
 ...
PMID:Beta-endorphin decreases fatigue and increases glucose uptake independently in normal and dystrophic mice. 1570 44

With the advent of potent combination antiretroviral therapy (ART), there has been a reduction in the incidence of wasting. However, few studies have investigated specific body composition changes associated with these treatments. This study aimed to investigate longitudinally the association of increasingly potent ART with changes in body cell mass and wasting utilizing bioelectric impedance analysis (BIA). In this longitudinal cohort study, 159 HIV-positive men were assessed semiannually from 1995 to 1997 for body composition utilizing BIA, CD4 lymphocyte count, HIV viral load, medical and depressive symptoms. Wasting was defined as body cell mass/height below the 90th percentile based on HIV positive norms. ART potency at each visit was scored utilizing published clinical guidelines, ranging from 1 (0-1 antiretrovirals) to 5 (3 or more antiretrovirals including a potent protease inhibitor). Viral resistance testing was not used. The mixed-effects model and the generalized estimating equations approaches were used to determine longitudinal correlates of body cell mass and of wasting, respectively. Over the 2 years of follow-up, potent combination ART use increased from 6% to 79%. Concurrently, a significant increase in mean body cell mass and a reduction in prevalence of wasting were seen, while total body weight, fat mass, and total body water did not change. Increasingly potent ART was associated with significant increases in body cell mass and reduction in wasting. Other significant correlates of increased body cell mass included higher CD4 count and decreased severity of HIV-related symptoms, fatigue and depression. The current study found that higher potency ART taken for relatively short term (2 years) was associated with an increase in body cell mass and a reduction in wasting and that these changes were associated with both medical (CD4, HIV symptoms) and behavioral (fatigue, depression) improvements. One caveat is this study did not distinguish among types of potent ART regimens. Given only some antiretrovirals appear linked to many body composition changes, regardless of their effect on viral load, it may be the type of regimen used that accounted for the relationship seen between viral load and body composition changes.
 ...
PMID:Increase in body cell mass and decrease in wasting are associated with increasing potency of antiretroviral therapy for HIV infection. 1585 93

Growth hormone (GH) treatment reverses the muscle loss allegedly responsible for diminished aerobic capacity and increased fatigue in patients with HIV-associated wasting. This study examined whether submaximal measures of physical performance can be used as objective measures of the functional impact of GH treatment-induced anabolism. We randomized 27 HIV-positive men [mean (SD) age, 43.9 (7.2) yr; body mass, 71.9 (10.4) kg; BMI, 23.1 (2.8) kg/m2] with unintentional weight loss despite antiretroviral therapy to receive GH (6 mg) or placebo in a double-blinded, placebo-controlled, cross-over trial with a 3-mo washout. Lean body mass (LBM), maximum oxygen uptake (Vo2 peak), ventilatory threshold (VeT), 6-min walk test (6MWT) distance and work, profile of mood states (POMS) fatigue and vigor scores, and Nottingham health profile (NHP) energy and physical mobility scores were measured. LBM significantly increased after 3 mo of GH treatment vs. placebo (means +/- SE, 3.7 +/- 0.6 vs. 0.3 +/- 0.4 kg; P < 0.001). VeT significantly improved (17.6 +/- 3.7 vs. -5.9 +/- 2.5%; P < 0.001), but Vo2 peak did not change significantly. 6MWT distance improved (24.9 +/- 9.7 vs. 19.9 +/- 11.6 m; P > 0.05) and 6MWT work increased significantly more after 3 mo of GH treatment (33.3 +/- 8.8 vs. 16.5 +/- 7.5 kJ; P < 0.05). POMS scores of fatigue and vigor and the NHP score of energy improved, yet the changes were not statistically significant. GH treatment improved VeT linearly to the increase in LBM (r =0.43, P = 0.037) and 6MWT work (r = 0.51, P = 0.008), and the increase in 6MWT work correlated with increase in LBM (r = 0.45, P = 0.024). Improvement in 6MWT work above the median (27.3 kJ) showed a decrease in fatigue (r = -0.62, P = 0.024). We concluded that GH treatment-induced LBM gains in HIV-associated wasting were functionally relevant, as determined by effort-independent submaximal measures of cardiopulmonary exercise testing.
 ...
PMID:Anabolic growth hormone action improves submaximal measures of physical performance in patients with HIV-associated wasting. 1588 28

Cardiac cachexia is a serious complication of chronic heart failure which is characterized by complex changes that overall lead to a catabolic/anabolic imbalance resulting in body wasting and a poor prognosis. The wasting process affects all body components, but particularly the skeletal musculature, causing extreme fatigue and weakness, especially in cachectic heart failure patients. Available evidence suggests that several pathophysiologic pathways play a role in the muscle wasting process. Metabolic, neurohormonal, and immune abnormalities lead to an altered regulation of proliferation, differentiation, apoptosis, and metabolism in skeletal muscle, finally resulting in deterioration of the underlying cause with symptomatic exercise intolerance. Possible treatment strategies against muscle wasting and cachexia in chronic heart failure are also described here. As there is no validated therapy for cardiac cachexia yet, further research is necessary to find more therapeutic options for the wasting process.
 ...
PMID:Muscle wasting in cardiac cachexia. 1592 19

Cachexia is among the most debilitating and life-threatening aspects of cancer, and is more common in children and elderly patients. Associated with anorexia, fat and muscle tissue wasting, psychological distress, and a lower quality of life, cachexia arises from a complex interaction between the cancer and the host. This process results from a failure of the adaptive feeding response seen in simple starvation and includes cytokine production, release of lipid-mobilizing and proteolysis-inducing factors, and alterations in intermediary metabolism. Cytokines play a pivotal role in long-term inhibition of feeding by mimicking the hypothalamic effect of excessive negative feedback signaling from leptin, a hormone secreted by adipose tissue, which is an integral component of the homeostatic loop of body weight regulation. This could be done by persistent inhibition of feeding-stimulatory circuitry including neuropeptide Y. Cachexia should be suspected in patients with cancer if an involuntary weight loss of greater than five percent of premorbid weight occurs within a 3-6-month period. The two major options for pharmacological therapy have been either progestational agents or corticosteroids. However, knowledge of the mechanisms of cancer anorexia-cachexia syndrome has led to, and continues to lead to, effective therapeutic interventions for several aspects of the syndrome. These include antiserotonergic drugs, gastroprokinetic agents, branched-chain amino acids, eicosapentanoic acid, cannabinoids, melatonin, and thalidomide-all of which act on the feeding-regulatory circuitry to increase appetite and inhibit tumor-derived catabolic factors to antagonize tissue wasting and/or host cytokine release. The outcomes of drug studies in cancer cachexia should focus on the symptomatic and quality-of-life advantages rather than simply on nutritional end points, since the survival of cachexia cancer patients may be limited to weeks or months due to the incurable nature of the underlying malignancy. Communication among physicians and other health care professionals provides the patient with a multidisciplinary approach to care. The patient record will be an excellent resource to document a plan of care and patient responses to treatment. Psychological distress and psychiatric disorders are common among cancer patients. These problems are also as common among the family members of people with cancer. The use of psychological and behavioral interventions in cancer is increasing, and recent studies have suggested that some of these techniques may affect quality of life and, perhaps, survival rates. Evaluations of relaxation, hypnosis, and short-term group psychotherapy have suggested some benefit with regard to anorexia and fatigue, although the population most likely to benefit from these interventions has not yet been determined. Because weight loss shortens the survival time of cancer patients and decreases performance status, effective therapy would extend patient survival and improve quality of life.
 ...
PMID:[Recent development in research and management of cancer anorexia-cachexia syndrome]. 1598 10

Multicentric Castleman disease (MCD) is an atypical lymphoproliferative disorder characterized by systemic lymphadenopathy and constitutional inflammatory symptoms. Dysregulated overproduction of interleukin-6 is responsible for the clinical abnormalities. This multicenter prospective study was undertaken to evaluate the safety and efficacy of a humanized anti-human interleukin-6 (IL-6) receptor monoclonal antibody (MRA) in patients with MCD. We report here results of the first 60 weeks of the study enrolling 28 patients. The initial dosing period consisted of 8 infusions of 8 mg/kg MRA administered biweekly. Adjustments in the dose and treatment interval were allowed for each patient in an extension phase after 16 weeks. Within 16 weeks, treatment with MRA consistently alleviated lymphadenopathy and all the inflammatory parameters. Hemoglobin, albumin, and total cholesterol levels, high-density lipoprotein cholesterol values, and body mass index all increased significantly. In addition, fatigue diminished. Chronic inflammatory symptoms were successfully managed over 60 weeks. In 8 (28.6%) patients, the MRA dose was decreased or the treatment interval was extended without exacerbation. Eleven (73.3%) of 15 patients who had received oral corticosteroids before study entry were able to do well on a reduced corticosteroid dose. Most adverse events were mild to moderate in severity. MRA was tolerated well and significantly alleviated chronic inflammatory symptoms and wasting in patients with MCD.
 ...
PMID:Humanized anti-interleukin-6 receptor antibody treatment of multicentric Castleman disease. 1599 37


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>