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

The progressive deterioration in nutrition status frequently seen in cancer patients is often referred to as cancer cachexia. Unlike starvation, in which fat stores from adipose are depleted and protein is spared from skeletal muscle, neither fat nor protein is spared in cachexia. Cachexia affects nearly half of cancer patients, causing the clinical manifestations of anorexia, muscle wasting, weight loss, early satiety, fatigue, and impaired immune response. Cachexia does not only impede the response to chemotherapy but also is a major cause of morbidity and mortality. According to clinical studies, increasing caloric intake does not necessarily reverse cachexia. The pathophysiology of cachexia involves more complex mechanisms than simply caloric deficiency. The process appears to be mediated by circulating catabolic factors, either secreted by the tumor alone or in concert with host-derived factors, such as tumor necrosis factor-alpha (TNF-alpha), interleukins (IL-1 and IL-6), interferon (IFN-y), and leukemia inhibitory factor (LIF). The successful reversal of this process will require in-depth knowledge of the mechanisms involved, which will then enable the development of effective pharmacologic interventions that may not only improve quality of life, but more importantly, improve survival among cancer patients.
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PMID:The cancer cachexia syndrome: a review of metabolic and clinical manifestations. 1620 77

Although palliative sedation therapy is often required in terminally ill cancer patients to achieve acceptable symptom relief, empirical data supporting the ethical validity of this approach are lacking. The primary aim of this study was to systematically investigate whether empirical evidence supports the ethical validity of sedation. This was a multicenter, prospective, observational study, which was conducted by 21 specialized palliative care units in Japan. One-hundred two consecutive adult cancer patients who received continuous deep sedation were enrolled. Continuous deep sedation was defined as the continuous use of sedative medications to relieve intolerable and refractory distress by achieving almost or complete unconsciousness until death. Prior to the study, we conceptualized the ethical validity of sedation from the viewpoints of physicians' intent, proportionality, and autonomy. Sedation was performed mainly with midazolam and phenobarbital. The initial doses of midazolam and phenobarbital were 1.5 mg/hour and 20 mg/hour, respectively. Main administration routes were continuous subcutaneous infusion and continuous intravenous infusion, and no rapid intravenous injection was reported. Of 59 patients who received artificial hydration or could intake adequate fluids/foods orally before sedation, 63% received artificial hydration therapy after sedation, and in the remaining patients, artificial hydration was withheld or withdrawn due to fluid retention symptoms and/or patient wishes. Of 66 patients who were able to verbally express themselves, 95% explicitly stated that symptoms were intolerable. The etiologies of the symptoms requiring sedation were primarily related to the progression of the underlying malignancy, such as cancer cachexia and organ failure, and standard palliative treatments had failed: steroids in 68% of patients with fatigue, opioids in 95% of patients with dyspnea, antisecretion medications in 75% of patients with bronchial secretion, antipsychotic medications in 74% of patients with delirium, and opioids in all patients with pain. On the basis of the Palliative Prognostic Index, 94% of the patients were predicted to die within 3 weeks. Before sedation, 67% of the patients expressed explicit wishes for sedation. In the remaining 34 patients, previous wishes for sedation were noted in 4 patients, and in the other 30 patients, the families were involved in the decision-making process. The chief reason for patient non-involvement in the decision making was cognitive impairment. These data indicate that palliative sedation therapy performed in specialized palliative care units in Japan generally followed the principles of double effect, proportionality, and autonomy.
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PMID:Ethical validity of palliative sedation therapy: a multicenter, prospective, observational study conducted on specialized palliative care units in Japan. 1625 95

Cachexia, a wasting condition often seen in advanced cancer, is often confused with anorexia but they are two separate conditions. It is evident that cachexia frequently leads to anorexia but anorexia alone cannot cause cachexia. The cachexia syndrome is weight loss with a specific cause--the action of cytokines, chemical messengers that are produced both by the body in response to the tumour and by the tumour to ensure its growth and spread. Treatment of cachexia is very difficult. Drugs to improve appetite have little effect, however, supplementing the diet with fish oils and vitamin E seems to be beneficial. Increasing a patient's level of exercise, even if bed-bound, does seem to have a positive effect and helps to synthesize skeletal muscle protein and delay the ravages of cachexia. Increasing exercise also has a positive effect on fatigue levels, a side-effect of cachexia.
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PMID:Understanding cachexia and excessive weight loss in cancer. 1630 22

Cancer is a major cause of morbidity and mortality throughout the world. It is the second most frequent cause of death in Europe and is becoming the leading cause of death in old age. Patients with cancer will develop a large number of physical symptoms. Malnutrition and weight loss are common and are due to a variety of mechanisms involving the tumour, the host response to the tumour, and anticancer therapies. Inadequate intake of energy and nutrients alone is unable to account for the substantial changes in nutritional status seen in patients with cancer. In advanced cancer, cachexia often occurs. This complex multifactorial syndrome is associated with metabolic abnormalities, anorexia, early satiety and reduced food intake, depletion of lean body mass, muscle weakness, oedema, fatigue, impaired immune function, and declines in attention span and concentration. The development and implementation of screening and assessment tools is essential for effective nutritional intervention and management of patients with cancer. Proactive nutritional interventions should ideally form an integral part of cancer therapy, with the aim of improving clinical outcomes and quality of life. This supplement brings together a collection of papers discussing various topics regarding nutrition in cancer.
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PMID:Cancer-associated malnutrition: an introduction. 1643 56

Cancer-associated malnutrition can result from local effects of a tumour, the host response to the tumour and anticancer therapies. Although cancer patients often have reduced food intake (due to systemic effects of the disease, local tumour effects, psychological effects or adverse effects of treatment), alterations in nutrient metabolism and resting energy expenditure (REE) may also contribute to nutritional status. Several agents produced by the tumour directly, or systemically in response to the tumour, such as pro-inflammatory cytokines and hormones, have been implicated in the pathogenesis of malnutrition and cachexia. The consequences of malnutrition include impairment of immune functions, performance status, muscle function, and quality of life. In addition, responses to chemotherapy are decreased, chemotherapy-induced toxicity and complications are more frequent and severe, and survival times are shortened. Depression, fatigue and malaise also significantly impact on patient well-being. In addition, cancer-related malnutrition is associated with significant healthcare-related costs. Nutritional support, addressing the specific needs of this patient group, is required to help improve prognosis, and reduce the consequences of cancer-associated nutritional decline.
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PMID:The causes and consequences of cancer-associated malnutrition. 1643 58

A major goal of palliative medicine is to control symptoms that interfere with quality of life. Identification of symptoms that occur together (cluster) may aid in symptom management, resulting in greater therapeutic benefit to the patient. An analysis of 25 symptoms from 922 patients with advanced cancer was undertaken to determine if symptom clusters could be identified. Cluster analysis was done using an agglomerative hierarchical method with average linkage; the absolute value of the correlation between pairs of symptoms was used as the measure of similarity. A correlation of >or=0.68 was used to define the final clusters. Seven clusters were identified: (1) fatigue: anorexia-cachexia; (2) neuropsychological; (3) upper gastrointestinal; (4) nausea and vomiting; (5) aerodigestive; (6) debility; (7) pain. Recognition of symptom clusters should help understand symptom pathophysiology and target therapies that perhaps can be used to relieve multiple symptoms in that cluster. This could result in improved quality of life for patients with advanced cancer and perhaps reduce polypharmacy, lessen drug side effects, and have pharmacoeconomic benefits.
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PMID:Symptom clustering in advanced cancer. 1648 50

Although we have made steady improvements in the survival rates of patients with advanced-stage lung cancer, the majority of patients still experience distress and suffering. Although the symptom burden is greatest in patients in the end stages of life, many patients living with lung cancer suffer from troubling symptoms and side effects of therapy. Even long-term survivors with early-stage non-small-cell lung cancer (NSCLC) often experience respiratory symptoms, such as dyspnea and cough. Because of the high prevalence of NSCLC and the frequency with which it presents in an incurable stage, symptom management is a large component of the care of these patients. Dyspnea, cough, fatigue, anorexia/cachexia, and pain are the most common symptoms in patients with advanced-stage NSCLC. Cancer-directed therapy can improve some of these symptoms but often incompletely and temporarily. Therefore, comprehensive care of patients with advanced-stage NSCLC must include therapies targeted at these difficult and distressing symptoms.
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PMID:Comprehensive symptom management in patients with advanced-stage non-small-cell lung cancer. 1651 77

Tumor-induced skeletal muscle wasting (SMW) contributes to the fatigue and weakness experienced by persons with cancer cachexia. Tumor necrosis factor-alpha (TNFa) and cyclooxygenase (COX) activity have been implicated in SMW in some animal models of cancer cachexia. We report that indomethacin, a nonspecific inhibitor of COX, and NS398, a specific inhibitor of COX2, preserved muscle mass and reduced type 1 TNF receptors in muscles of mice bearing the Lewis lung carcinoma, but not in mice bearing the B16 melanoma. These data suggest that tumor-induced SMW can occur via a COX2-independent pathway. The COX2-dependent pathway may involve reducing the catabolic effects of TNFa in muscle. Further study is needed to understand the relationship between COX and SMW, and whether patients with cancer cachexia might benefit from COX inhibitors.
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PMID:Inhibitors of COX activity preserve muscle mass in mice bearing the Lewis lung carcinoma, but not the B16 melanoma. 1653 83

In advanced stages of polycystic liver disease, often associated with polycystic kidney disease, a curative therapy is liver or combined liver-kidney transplantation. However, little is known about long-term outcome and quality of life. Between 1990 and 2003, 36 patients (32 female, 4 male) with polycystic liver or combined liver-kidney disease underwent liver (n = 21) or liver-kidney (n = 15) transplantation at our center. Main indications for liver transplantation were cachexia, muscle atrophy, loss of weight, recurrent cyst infections, portal hypertension, and ascites. Apart from clinical parameters, 2 anonymous questionnaires (standard short form 36 and self-designed) addressing quality of life and social status were evaluated. Five patients (14 %) died due to sepsis or myocardial infarction with pneumonia, all within 61 days after transplantation. The follow-up time of the remaining 31 patients ranged from 5 to 156 months, with a mean of 62 months. Of the 23 (74%) answered the questionnaires, 91% of patients felt "much better" or "better," only 9% felt "worse" than before, and 52% of patients participated in sports regularly. Fatigue, physical fitness, loss of appetite, and vomiting improved significantly after transplantation. Physical attractiveness and interest in sex increased as well. Professional occupation did not change for 71% of patients. Family situation before and after transplantation changed in 1 case only. Finally, 78% of patients said they would opt for transplantation again, while 17% were undecided; 1 patient would not repeat transplantation. In conclusion, patients with advanced polycystic liver or polycystic liver-kidney disease have an excellent survival rate and an improved quality of life after liver or combined liver-kidney transplantation.
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PMID:Outcome and quality of life in patients with polycystic liver disease after liver or combined liver-kidney transplantation. 1686 56

Discovering approaches to maintain or improve muscle function (fatigue resistance) in patients with cachexia, postoperative weakness, and sarcopenia is of clinical importance. beta(2)-Agonist treatment increases muscle mass, yet it alters fiber proportions such that the net consequences on muscle function remain unclear. In the present study, we focus on the contractile and metabolic consequences of chronic treatment with the beta(2)-agonist prodrug BRL-47672 (BRL). Gastrocnemius-plantaris-soleus (GPS) muscles were harvested at rest and studied for fatigue characteristics during 4 and 20 s of isometric stimulation (30 Hz; 10 V; 200 ms) using the perfused hind limb model. BRL treatment increased GPS mass by 21% (P < 0.05), whereas greater fatigue occurred during 20 s of contraction (45% less work; P < 0.05). Phenotypically, BRL resulted in 17% more type IIb myosin heavy chain protein expression (P < 0.001) and greater adenine nucleotide catabolism during 20 s of contraction (P < 0.05). Chronic BRL treatment impaired maximal lipid oxidation capacity by 30% (P < 0.05) and reduced glutamate dehydrogenase activity by 15% (P < 0.05). We conclude that beta(2)-agonist induced muscle hypertrophy may be clinically limited as impaired energy metabolism and function occur, presumably as a consequence of the shift in muscle phenotype.
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PMID:Chronic treatment with the beta(2)-adrenoceptor agonist prodrug BRL-47672 impairs rat skeletal muscle function by inducing a comprehensive shift to a faster muscle phenotype. 1684 43


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