Erythropoietin (EPO), recognized for its central role in erythropoiesis, also mediates neuroprotection when the recombinant form (r-Hu-EPO) is directly injected into ischemic rodent brain. We observed abundant expression of the EPO receptor at brain capillaries, which could provide a route for circulating EPO to enter the brain. In confirmation of this hypothesis, systemic administration of r-Hu-EPO before or up to 6 h after focal brain ischemia reduced injury by Ϸ50 -75%. R-Hu-EPO also ameliorates the extent of concussive brain injury, the immune damage in experimental autoimmune encephalomyelitis, and the toxicity of kainate. Given r-Hu-EPO's excellent safety profile, clinical trials evaluating systemically administered r-Hu-EPO as a general neuroprotective treatment are warranted. E rythropoietin (EPO) and its receptor (EPO-R) function as primary mediators of the normal physiologic response to hypoxia. EPO, a glycoprotein that increases red cell mass to improve tissue oxygenation, is produced by the kidney in response to hypoxia. Recombinant human EPO (r-Hu-EPO) is effective and widely used for the treatment of anemia associated with renal failure, HIV infection, cancer, and surgery. However, like other members of the cytokine superfamily to which EPO and its receptor belong, both are expressed by other tissues, including the nervous system. Similar to its regulation in the periphery, EPO within the central nervous system is inducible by hypoxia (1-4). An in vivo neuroprotective function for EPO has been demonstrated by the observation that direct intracerebraventricular injection of r-Hu-EPO in advance of hypoxic͞ ischemic stress offers significant protection of neuronal tissue (5-7). A critical neuroprotective role for endogenous EPO in the central nervous system has been confirmed by the administration of soluble EPO-R, which neutralizes EPO, consequently exacerbating ischemic stress and increasing tissue injury (7).Hypoxia may not be the only relevant stimulus for brain EPO production, however, as metabolic disturbances, including hypoglycemia and strong neuronal depolarization, generate mitochondrial reactive oxygen species that may increase brain EPO expression through hypoxia inducible factor 1 (8). EPO may thus protect nervous tissue under any condition characterized by a relative deficiency of ATP in the face of increased metabolic demands. EPO has been shown to exhibit classic neurotrophic effects in vivo and in vitro (2, 9-11). The mechanism of action of EPO in erythropoiesis, neuroprotection, and neurotrophic effects ultimately may involve activation of the bcl-x family of antiapoptotic genes, promoting survival rather than apoptosis (12)(13)(14).Despite the demonstrated benefit of intrathecally administered r-Hu-EPO in preventing ischemic neuronal damage, direct delivery of r-Hu-EPO into the brain is not a practical approach in most clinical contexts. Systemic delivery of r-Hu-EPO has not been evaluated because of the perception that the brain EPO system is parallel and distinct from the control ...
Purpose. This survey was designed to confirm the prevalence and duration of fatigue in the cancer population and to assess its physical, mental, social, and economic impacts on the lives of patients and caregivers.Patients and Methods. A 25-minute telephone interview was completed with 379 cancer patients having a prior history of chemotherapy. Patients were recruited from a sample of 6,125 households in the United States identified as having a member with cancer. The median patient age was 62 years, and 79% of respondents were women. Patients reporting fatigue at least a few times a month were asked a series of questions to better describe their fatigue and its impact on quality of life.Results. Seventy-six percent of patients experienced fatigue at least a few days each month during their most recent chemotherapy; 30% experienced fatigue on a daily basis. Ninety-one percent of those who experienced fatigue reported that it prevented a "normal" life, and 88% indicated that fatigue caused an alteration in their daily routine. Fatigue made it more difficult to participate in social activities and perform typical cognitive tasks. Of the 177 patients who were employed, 75% changed their employment status as a result of fatigue. Furthermore, 65% of patients indicated that their fatigue resulted in their caregivers taking at least one day (mean, 4.5 days) off work in a typical month. Physicians were the health care professionals most commonly consulted (79%) to discuss fatigue. Bed rest/ relaxation was the most common treatment recommendation (37%); 40% of patients were not offered any recommendations.Conclusions. Cancer-related fatigue is common among cancer patients who have received chemotherapy and results in substantial adverse physical, psychosocial, and economic consequences for both patients and caregivers. Given the impact of fatigue, treatment options should be routinely considered in the care of patients with cancer.
Background: Erythropoietin (EPO) and its receptor play a major role in embryonic brain, are weakly expressed in normal postnatal/adult brain and up-regulated upon metabolic stress. EPO protects neurons from hypoxic/ ischemic injury. The objective of this trial is to study the safety and efficacy of recombinant human EPO (rhEPO) for treatment of ischemic stroke in man. Materials and Methods: The trial consisted of a safety part and an efficacy part. In the safety study, 13 patients received rhEPO intravenously (3.3 ϫ 10 4 IU/50 ml/30 min) once daily for the first 3 days after stroke. In the double-blind randomized proof-of-concept trial, 40 patients received either rhEPO or saline. Inclusion criteria were age Ͻ80 years, ischemic stroke within the middle cerebral artery territory confirmed by diffusion-weighted MRI, symptom onset Ͻ8 hr before drug administration, and deficits on stroke scales. The study endpoints were functional outcome at day 30 (Barthel Index, modified Rankin scale), NIH and Scandinavian stroke scales, evolution of
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