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Query: UMLS:C0015672 (fatigue)
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Carnitine is a conditionally essential metabolite that plays a critical role in cell physiology by participating in transesterification reactions and preventing organic acid accumulation. A number of disease states are characterized by carnitine depletion that may lead to metabolic and clinical disturbances. In maintenance hemodialysis, carnitine is lost through dialytic membranes, leading in selected patients to carnitine depletion with a relative increase of the esterified forms. Carnitine supplementation after or during dialysis counteracts such alterations and may be associated with some clinical benefits. Recent meta-analyses of the literature indicate that carnitine supplementation in hemodialysis patients may improve the hematological status (allowing a reduction of the requirement for erythropoietin), the exercise tolerance, the plasma lipid profile, and the intradialytic symptoms. In addition, carnitine supplementation may improve cardiac functions, protein metabolism, and insulin resistance. Carnitine supplementation has been recently approved by the US Food and Drug Administration not only for the treatment, but also for the prevention of carnitine depletion in dialysis patients. Furthermore, clinical guidelines developed by both American and European nephrological societies suggest that a trial with carnitine supplementation could be recommended in selected dialysis patients who do not adequately respond to standard therapy for certain conditions, such as severe and persistent muscle cramps or hypotension during dialysis, lack of energy affecting quality of life, skeletal muscle weakness or myopathy, cardiomyopathy, and anemia of uremia unresponsive to or requiring large doses of erythropoietin.
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PMID:Carnitine metabolism in uremia. 1157 25

Fatigue is prominent in cancer patients and probably multifactorial in origin. Factors contributing to fatigue include anemia, weight loss, fever, pain, medication, and infection. In cancer patients, many of these factors are influenced by a frequently disrupted balance between endogenous cytokine levels and their natural antagonists. Indeed, cancer cells and the immune system appear to overexpress a range of cytokines in patients with malignancies. Some of these cytokines act as autocrine or paracrine growth factors for the neoplastic tissue while simultaneously causing secondary symptoms related to fatigue. For instance, cancer-associated anemia may be due to a blunted erythropoietin response and/or cytokines (interleukin-1 [IL-1], IL-6, tumor necrosis factor-alpha [TNF-alpha]), which suppress erythropoiesis. Cancerous cachexia, a wasting syndrome and a hallmark of cancer, can be attributed to loss of appetite or enhanced energy expenditure. Several different interleukins, as well as TNF, interferon-gamma, and leukemia inhibitory factor, act as cachectins in animal models. Similarly, fever and night sweats are influenced by pyrogenic cytokines. Recently, molecules that function as cytokine antagonists have been identified. These molecules may be exploitable in combating the components of cancer-related fatigue, and may inhibit tumor growth as well.
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PMID:The role of cytokines in cancer-related fatigue. 1159 87

Cancer-related causes of anaemia include anaemia of chronic disorders, infections, autoimmune haemolysis associated with malignant conditions, bone marrow invasion by the tumour or clonogenic marrow dysfunction, iron, folate, or vitamin B 12 deficiency and bleeding from tumour erosion. Treatment-related anaemia results from chemotherapy, radiotherapy and bone marrow fibrosis. Severe anaemia increases the burden of treatment, contributes to fatigue, reduces the quality of life and may also delay or limit further treatment. Blood transfusion is currently the most common form of treatment and patients rarely require transfusion unless the haemoglobin is less than 8 g/l. It is often difficult to predict which patients will develop anaemia and require treatment, but the proportion of patients receiving transfusions increases markedly if the pre-treatment haemoglobin concentration is below 10 g/dl. Four studies have systematically evaluated the effects of erythropoietin on anaemia in lung cancer patients and each of these trials is likely to contribute information concerning the clinical benefit of erythropoietin in treating or preventing treatment-related or disease-related anaemia. Most of the improvements in quality of life observed with erythropoietin administration occurred with haemoglobin levels between 10 and 12 g/dl, and not with levels between 7 and 10 g/dl, with a plateau effect above 12 g/dl. Consequently, a 'functional' level of haemoglobin that appears to be more important is 12 g/dl, because it may be favourably associated with a significant improvement in fatigue compared with lower haemoglobin levels. This 'functional' level would be in keeping with the body's physiological erythropoietin response.
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PMID:Role of erythropoietin in the treatment of lung cancer associated anaemia. 1174 10

Anaemia is a common complication of cancer and cancer therapies, and fatigue is one of the most common symptoms of anaemia, disrupting functional performance and reducing overall quality of life. The positive effects of treating renal patients with recombinant human erythropoietin are well documented. This case report series details the specific effects of fatigue on individual patients with cancer and their way of life, and describes their significant improvement in lifestyle following the reversal of anaemia using recombinant human erythropoietin, epoetin alfa.
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PMID:Improvement in quality of life for cancer patients treated with epoetin alfa. 1182 81

A review of research into cancer-related fatigue undertaken since 1995 is presented. The manner in which such fatigue varies with cancer diagnosis, stage of disease and anti-cancer treatment is discussed, and the causes of cancer-related fatigue are categorized according to whether they are cancer-specific, common to other chronic illnesses or common to the general population. Interventions to alleviate fatigue are discussed in terms of whether they are pharmacological or non-pharmacological in nature. It is concluded that cancer-related fatigue is a common problem with a major impact on quality of life. It shares a common aetiology with other forms of fatigue. Graded aerobic exercise has been shown in randomized controlled trials to be an effective intervention in specific patient groups. Less direct evidence supports the use of psychological interventions, but there is very little evidence to support the use of pharmacological treatment, with the possible exception of erythropoietin therapy for anaemic patients undergoing chemotherapy.
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PMID:The measurement, causes and effective management of cancer-related fatigue. 1192 40

Anemia is a common disorder in patients with cancer and can be caused by the disease itself or by cancer-related therapy. The cardinal symptom of anemia, fatigue, is the most commonly reported symptom in patients with cancer and has profound effects on patient well-being and quality of life. Until recently, blood transfusions were the mainstay of management of cancer-related anemia, despite attendant risks of transfusion-related reactions and transmission of infection. Recombinant human erythropoietin (epoetin-alpha), an effective alternative to blood transfusion, has been shown to improve hematologic parameters, including hemoglobin levels, Hematocrit, and transfusion requirements. Clinical trials have also suggested that this intervention has a positive impact on the quality of life of patients with cancer. The literature published between November 2000 and October 2001 continues to support a positive effect of epoetin-alpha therapy on the quality of life of patients with cancer and includes investigations of dosing schedules more convenient for patients and trials of longer-acting versions of epoetin-alpha, such as the novel erythropoiesis-stimulating protein. Future studies that incorporate measures of patient-reported outcomes and rigorous methodologic designs are needed to strengthen and elucidate this association between these pharmacologic therapies for cancer-related anemia and quality of life.
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PMID:Methods and progress in assessing the quality of life effects of supportive care with erythropoietin therapy. 1195 70

Human immunodeficiency virus (HIV)-infected patients experience a range of haematological complications including anaemia, neutropenia, lymphopenia and thrombocytopenia. Anaemia is a prognostic marker of future disease progression or death, independent of CD4 and viral load. Recovery from anaemia reduces the risk of disease progression to approximately the same level as seen among patients who have never had anaemia. Additionally, anaemia impacts a range of dimensions of quality of life, most commonly through fatigue. Anaemia can be caused by a range of mechanisms including infections, neoplasms, dietary deficiencies, blood loss and medication. Histologically, bone marrow hypoproliferation and dysplasia are the most commonly seen. Both AZT and d4T induce macrocytosis, however, AZT, but not d4T, has broader myelosuppressive effects both in vitro and in vivo. The management of anaemia typically includes correction of the underlying cause(s) and blood transfusion or erythropoietin. However, blood transfusions and iron supplementation may activate HIV expression and possibly worsen immunosuppression. Recombinant human erythropoietin (rHuEPO) is an effective means of improving haemoglobin and reducing transfusion requirements in patients who have low (< 500 IU/L) endogenous erythropoietin levels.
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PMID:Anaemia in persons with HIV infection: prognostic marker and contributor to morbidity. 1199 79

Breast cancer patients receiving chemotherapy often exhibit anemia, which contributes to symptoms such as fatigue, compromising quality of life (QOL). The present subset analysis assessed the effects of recombinant human erythropoietin (rHuEPO, epoetin alfa) on anemia and QOL in approximately 1300 patients with breast cancer, who were derived from 3 large, community-based clinical trials of epoetin alfa in anemic chemotherapy patients with various malignancies. Epoetin alfa effectively and safely corrected anemia and improved QOL scores on the Linear Analogue Self-Assessment, which measures energy, ability to perform daily activities, and QOL. Clinical, laboratory, and QOL improvements were qualitatively and quantitatively similar to those reported in the larger populations with various tumor types. The efficacy and safety of epoetin alfa did not vary according to dosing frequency (1 vs. 3 times weekly). Epoetin alfa is, therefore, effective and safe in the management of anemia in patients with breast cancer treated with chemotherapy.
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PMID:Benefits of epoetin alfa in anemic breast cancer patients receiving chemotherapy. 1202 Mar 95

Anemia is a frequent complication of cancer and its treatment. It often impairs the functional status of patients and results in decreased functional capacity and quality of life. Its etiologies are multiple, including chronic inflammation, hemorrhage, nutritional deficiencies, hemolysis, bone marrow suppression by chemotherapy, or infiltration by tumor. It can manifest as feelings of weariness, tiredness, muscular weakness, dysphoric mood, somnolence, or impaired cognitive functioning. In gynecologic patients, the incidence of anemia has been reported to be as high as 80% depending on chemotherapy regimen. Given the various consequences of a low hemoglobin level, the importance of increasing or maintaining hemoglobin levels and ameliorating the symptoms is apparent. Clinical studies have demonstrated that the administration of recombinant human erythropoietin (rHuEPO, epoetin alfa) is effective and safe in increasing hemoglobin levels and improving the overall quality of life in patients with gynecologic cancers undergoing chemotherapy. Therefore, epoetin alfa treatment should be considered in this patient population.
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PMID:The impact of anemia and its treatment on patients with gynecologic malignancies. 1208 47

Anemia is a common complication in patients with hematologic malignancies, and is caused by a variety of mechanisms, including neoplastic cell infiltration into the bone marrow, hemolysis, nutritional deficiencies, and defects in erythropoiesis as a result of the disease itself or cytotoxic therapy. The anemia associated with multiple myeloma is caused by inadequate erythropoietin levels consequent to renal impairment and the effect of inflammatory cytokines. The degree of anemia can have prognostic importance, as is the case with multiple myeloma, or be a significant indicator of disease stage, as noted with chronic lymphocytic leukemia. Anemia results in fatigue, exhaustion, dizziness, headache, dyspnea, and decreased motivation, seriously affecting a patient's quality of life. Since anemia is so prevalent in hematologic malignancy patients, its treatment must be an integral part of disease management, to improve quality of life and to possibly increase potential survival. Clinical studies have shown that effectively treating anemia and increasing hemoglobin levels using recombinant human erythropoietin (rHuEPO, epoetin alfa) has a significant effect on transfusion requirements and quality of life.
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PMID:The effects of anemia in hematologic malignancies: more than a symptom. 1208 53


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