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Anemia is common in patients infected with the human immunodeficiency virus (HIV). The etiology is often multifactorial and may include the HIV infection itself, opportunistic infections, cancer, medications (particularly zidovudine and sulfa-containing drugs), or anemia of chronic disease. Epoetin alfa therapy may play a supportive role in some HIV-infected patients by increasing hemoglobin, decreasing fatigue, and reducing the need for exposure to red blood cell transfusions. A large, placebo-controlled trial in the United States for anemic patients with the acquired immunodeficiency syndrome taking zidovudine demonstrated a statistically significant improvement in hematocrit in patients treated with epoetin alfa compared with placebo. Transfusion requirements decreased in epoetin alfa-treated patients over a 3-month period compared with placebo with a trend toward improvement in quality of life. Epoetin alfa was effective, however, only in patients whose pretreatment erythropoietin levels were less than 500 mU/mL. These advantages of epoetin alfa treatment may become especially important as HIV becomes more of a chronic disease, with the concern that red blood cell transfusion may accelerate progression of HIV.
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PMID:Experience with epoetin alfa and acquired immunodeficiency syndrome anemia. 967 34

Oncologists have several reasons for trying to maintain or increase hemoglobin levels in their patients during therapy. Relief of the symptoms of anemia, including fatigue and dyspnea, are traditional, well-accepted indications. A newer rationale is to enhance the efficacy of radiation therapy and/or chemotherapy in controlling tumors. A laboratory animal study found that administration of recombinant human erythropoietin (rHuEPO) increased intratumoral median oxygen levels and diminished the proportion of measurements in the very low (< 3 mm Hg) range. Hemoglobin level is a strong independent prognostic factor for tumor control by radiation therapy. The hemoglobin level at the end of radiation therapy is a stronger prognostic factor than is the hemoglobin level at the start of therapy. Numerous clinical trials have utilized rHuEPO during radiation with or without concurrent chemotherapy. All 4 trials which enrolled patients with low hemoglobin levels (< 12 to 13.5 g/dl) found that rHuEPO significantly increased hemoglobin within 2 weeks and that hemoglobin levels continued to rise until the end of rHuEPO treatment. rHuEPO was efficacious in limiting the decrease in hemoglobin and use of packed red blood cell transfusion in the one reported trial in which it was used in patients with initially normal hemoglobin levels during intensive concurrent radiation and chemotherapy. One trial found a statistically significant improvement in complete pathologic response rate after neoadjuvant chemoradiotherapy with the use of rHuEPO. rHuEPO has a potentially large to play in the care of the cancer patient.
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PMID:Clinical trial experience using erythropoietin during radiation therapy. 987 44

Anemia represents a common side effect of cancer chemotherapy, and results in diminished overall well-being as well as side effects such as dyspnea, fatigue and decreased appetite. Treatment options for chemotherapy-induced anemia are transfusion of red blood cells and s.c. erythropoietin. Although transfusion is generally well tolerated, patients usually experience fluctuating hemoglobin levels because of hesitancy to transfuse to normal hemoglobin levels. Additionally, concerns persist related to the safety of blood products, including the transmission of blood-borne pathogens, immunomodulation by transfusion and severe allergic reactions, despite advances in transfusion medicine. Erythropoietin is an effective alternative to transfusion in many patients and allows for a more consistent hemoglobin level. The costs associated with the drug have limited its use. In addition, patient preferences for the two treatment options have not been investigated. Economic analyses, including consideration of the costs associated with medical care as well as the consequences, will be essential in evaluating the potential of transfusions and erythropoietin in treating the anemia associated with cancer chemotherapy.
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PMID:Recombinant erythropoietin and blood transfusions in cancer chemotherapy-induced anemia. 989 Jul 4

Cancer-related anaemia has a number of causes, not least the underlying malignancy itself which plays a role in suppressing erythropoiesis. Anaemia is often exacerbated by cancer treatments, in particular routinely used cytotoxic chemotherapy. Chronic anaemia of cancer is often characterized by inappropriately low levels of endogenous erythropoietin for the degree of anaemia, and manifests clinically with generalized hypoxia and resultant severe fatigue. Epoetin alfa is one recombinant form of erythropoietin, the primary human growth factor responsible for promoting proliferation and survival of erythroid progenitor cells. Epoetin alfa has been widely studied for the treatment of anaemia associated with renal failure and is now recognized as having significant potential in the management of cancer-related anaemia. Studies suggest that epoetin alfa is an effective treatment in a proportion of cancer patients with symptomatic anaemia. It also appears useful for the prevention of chemotherapy-induced anaemia. Studies in a number of different cancer settings have shown that epoetin alfa significantly increases haemoglobin and haematocrit, reduces transfusion requirements and improves quality of life for the patient.
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PMID:Epoetin in cancer-related anaemia. 1033 73

In summary, sexual dysfunction is a common finding in both men and women with chronic renal failure. Common disturbances include erectile dysfunction in men, menstrual abnormalities in women, and decreased libido and fertility in both sexes. These abnormalities are primarily organic in nature and are related to uremia as well as the other comorbid conditions that frequently accompany the chronic renal failure patient. Fatigue and psychosocial factors related to the presence of a chronic disease are also contributory factors. Disturbances in the hypothalamic-pituitary-gonadal axis can be detected before the need for dialysis but continue to worsen once dialytic therapy is initiated. Impaired gonadal function is prominent in uremic men, whereas the disturbances in the hypothalamicpituitary axis are more subtle. By contrast, central disturbances are more prominent in uremic women. Therapy is initially directed toward optimizing the delivery of dialysis, correcting anemia with recombinant erythropoietin, and controlling the degree of secondary hyperparathyroidism with vitamin D. For many practicing nephrologists, sildenafil has become the first-line therapy in the treatment of impotence. In the hypogonadal man whose only complaint is decreased libido, testosterone may be of benefit. Regular gynecologic follow-up is required in uremic women to guard against potential complications of unopposed estrogen effect. Uremic women should be advised against pregnancy while on dialysis. Successful transplantation is the most effective means of restoring normal sexual function in both men and women with chronic renal failure.
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PMID:Sexual dysfunction in uremia. 1036 78

About 50% of cancer patients develop anemia; this incidence rises dramatically in patients with more advanced cancer or in those receiving chemotherapy or radiation therapy. Since the late 1980s, recombinant human erythropoietin (rHuEPO) has provided a safe and effective option for treating cancer-related anemia and fatigue. However, only about 50% of patients treated with rHuEPO adequately respond to therapy. In the chronic renal failure (CRF) population, true iron deficiency is the most common cause of an inadequate response to rHuEPO. Functional iron deficiency occurs when iron cannot be provided rapidly enough to meet the demands of rHuEPO-induced erythropoiesis, despite the presence of adequate bone marrow iron stores. It is hypothesized that functional iron deficiency can also occur in cancer patients receiving rHuEPO and may account for the lack of response in a proportion of the oncology population. Studies in CRF patients have shown that the administration of i.v. iron can correct functional iron deficiency more effectively than oral iron and may improve rHuEPO response. Therefore, it is important to monitor iron status and to address either true or functional iron deficiency prior to and during rHuEPO therapy to optimize the effect of rHuEPO in cancer patients. Studies are currently under way to determine the role of i.v. iron in treating cancer-related anemia.
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PMID:Supplemental Iron: A Key to Optimizing the Response of Cancer-Related Anemia to rHuEPO? 1038 16

The final stages of maturation of erythroid cells Into mature red blood cells are regulated by the growth factor erythropoietin. Circulating levels of erythropoietin are remarkably consistent across the range of normal hemoglobin levels; levels Increase markedly as hemoglobin declines below 12 g/dL In a manner suggesting that mechanisms in addition to the level of tissue oxygen are important in regulating increases in erythropoietin production and erythropoiesis. The erythropoietin receptor is found on a number of cell types in addition to erythroid progenitor cells, suggesting that erythropoietin may have specific biologic effects on other tissues, still to be carefully discerned. Clinical trials have demonstrated the effectiveness of recombinant human erythropoietin (epoetin alfa) in increasing hemoglobin level in iatrogenic and disease-related anemias. This increase has been associated with improving fatigue symptoms and enhancing overall quality of life. Questions remain, however, regarding the optimal increases in hemoglobin to be achieved in anemic patients with such therapy and whether optimal levels might vary in different patient groups.
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PMID:Overview: erythropoiesis, anemia, and the impact of erythropoietin. 1106 48

Anaemia, manifesting as fatigue, dizziness, dyspnoea and anorexia, is common among patients with cancer. A host of factors, such as neoplastic bone marrow infiltration, impaired haematopoiesis, autoimmune haemolysis, impaired endogenous erthropoietin production and treatment with cytotoxic agents contribute to the underlying pathology. Traditionally, blood transfusions have formed the mainstay of therapy for the treatment of cancer-related anaemia. Numerous clinical trials have subsequently confirmed the safety and therapeutic utility of recombinant human erythropoietin (rHuEPO) in anaemic cancer patients, including those with haematological malignancies, such as multiple myeloma and non-Hodgkin's lymphoma. Indeed, well over 50% of unselected patients treated with rHuEPO can be expected to respond with increases in haemoglobin level and/or elimination of transfusion need. In addition, a low baseline serum erythropoietin level can identify those patients with haematological malignancies having a very high likelihood of responding to rHuEPO therapy. These findings, in combination with the possibility of titrating to a lower, maintenance dose, have improved the cost-benefit relationship and thus support the use of rHuEPO as an appropriate alternative to blood transfusions for the management of anaemic patients with lymphoma and myeloma.
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PMID:The role of recombinant human erythropoietin in the management of anaemic cancer patients: focus on haematological malignancies. 1118 81

Anaemia is a common disorder in patients with cancer, occurring in 10-40% of cases, depending upon the tumour type and chemotherapy used. It is present in nearly all patients with leukaemia at some time in the disease and in 50% of patients with lymphoma after chemotherapy. Cancer-related anaemia appears to result from a range of factors including chronic inflammation, blood loss, nutritional deficiencies, haemolysis, bone marrow infiltration by malignant cells, low serum erythropoietin (EPO) levels, and a decrease of bone marrow responsiveness to EPO. The consequences of anaemia, namely fatigue and cardiovascular symptoms, can adversely affect patients' quality of life and may even alter their response to cancer treatment. Moreover, anaemia is often associated with the presence of several adverse prognostic parameters and is also itself a predictor of poor prognosis. Furthermore, anaemia and its symptoms can be exacerbated by cancer treatment. Until recently, blood transfusions have been the mainstay of treatment for cancer-related anaemia, despite the associated risks of transfusion-related reactions and transmission of infection. By increasing haemoglobin levels and haematocrit, treatment with recombinant human erythropoietin (rHuEPO) has been shown to reduce the need for blood transfusion in patients with haematological malignancies. It is recommended that rHuEPO be administered when a patient's haemoglobin level is at risk of falling below 8g/dL, and that treatment is maintained until levels rise above 13g/dL. Consideration of the detrimental effects of anaemia on cancer patients' physical and emotional well-being and therapeutic outcome suggests that rHuEPO therapy has the potential to provide substantial clinical benefits.
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PMID:The impact and management of anaemia in haematological malignancies. 1118 82

These guidelines propose a treatment algorithm in which patients are evaluated regularly for fatigue, using a brief screening instrument, and are treated as indicated by their fatigue level. The algorithm's goal is to identify and treat all patients with fatigue that causes distress or interferes with daily activities or functioning. Management of fatigue begins with primary oncology team members who perform the initial screening and either provide basic education and counseling or expand the initial screening to a more focused evaluation for moderate or higher levels of fatigue. At this point the patient is assessed for the five primary factors known to be associated with fatigue: pain, emotional distress, sleep disturbance, anemia, and hypothyroidism. If any of these conditions are present, it should be treated according to practice guidelines, and the patient's fatigue should be reevaluated regularly. If none of the primary factors is present or the fatigue is unresolved, a more comprehensive assessment is indicated--with referral to other care providers as appropriate. The comprehensive assessment should include a thorough review of systems, review of medications, assessment of comorbidities, nutritional/metabolic evaluation, and assessment of activity level. Management of fatigue is cause-specific when conditions known to cause fatigue can be identified and treated. When specific causes, such as infection, fluid and electrolyte imbalances, or cardiac dysfunction, cannot be identified and corrected, nonpharmacologic and pharmacologic treatment of the fatigue should be considered. Nonpharmacologic interventions may include a moderate exercise program to improve functional capacity and activity tolerance, restorative therapies to decrease cognitive alterations and improve mood state, and nutritional and sleep interventions for patients with disturbances in eating or sleeping. Pharmacologic therapy may include drugs such as antidepressants for depression or erythropoietin for anemia. A few clinical reports of the use of corticosteroids and psychostimulants suggest the need for further research on these agents as a potential treatment modalities in managing fatigue. Basic to these interventions, the effective management of cancer-related fatigue involves an informed and supportive oncology care team that assesses patients' fatigue levels regularly and systematically and incorporates education and counseling regarding strategies for coping with fatigue (Johnson, 1999), as well as using institutional fatigue management experts for referral of patients with unresolved fatigue.
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PMID:NCCN Practice Guidelines for Cancer-Related Fatigue. 1119 8


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