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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Polycythemia in CAPD patients has been rarely described. Over an eight year period, 4 out of 123 CAPD patients (3%) were identified as having Hct values exceeding 50% for 1 month or longer. All of the 4 patients were insulin dependent diabetics (4/47 diabetic patients, 8.5%). Charts were reviewed on 3 of these 4 patients. Polycythemia developed after a mean of 21 +/- 7 months on peritoneal dialysis. Prior to the development of polycythemia, ferritin levels were low and ferrous sulfate therapy was begun at a time the Hct values were 36 to 40%. Erythropoietin levels were obtained in 2 patients, and were 22 U/L (Hct 51%) and less than 5 U/L (Hct 55%). Renal ultrasound failed to show renal masses or cysts. One patient had a plasma volume of 2.1 L (normal 2.4-3.2 L); another patient was clinically volume depleted. Complications during the period of polycythemia included gangrenous feet requiring amputation in 2 patients, CVA in 2 patients, and splenic infarct in 1 patient. One patient died of cerebral thrombosis. We conclude that polycythemia is uncommon in CAPD patients and occurs most often in diabetic patients. Volume depletion and iron therapy may play a role in its etiology. In this high risk group of patients polycythemia may contribute to vascular complications and should be avoided.
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PMID:Polycythemia in diabetic patients on CAPD. 168 Apr 62

Recombinant human erythropoietin is a major advance in the management of patients with chronic renal failure. The sustained dose-dependent rise in haematocrit which it produces effectively abolishes symptoms of anaemia, but at the cost of an increase in blood viscosity. This in turn predisposes to increased vascular resistance and the development of hypertension. Over half of all deaths of patients with end-stage renal failure are from cardiovascular disease, notably myocardial infarction, heart failure, and stroke, for which hypertension is a known risk factor. Erythropoietin-related increases in blood pressure are therefore of particular concern, and seem to be most severe in previously hypertensive patients. There is now a need to establish the optimum rate and extent of rise of haematocrit required to alleviate symptoms without incurring undue risk.
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PMID:Hypertension, blood viscosity, and cardiovascular morbidity in renal failure: implications of erythropoietin therapy. 289 90

Recombinant human erythropoietin is widely used in chronic dialysis patients. However, the long-term effect, especially on the incidence of cardiovascular disease, has not been critically evaluated. We observed the annual incidence of stroke and acute myocardial infarction from April 1988 through March 1993 in Okinawa, Japan. Until April 1990, erythropoietin was not generally used. Therefore, we have two periods: pre-erythropoietin, April 1988 through March 1990, and post-erythropoietin, April 1990 through March 1993. Two thousand one hundred and sixteen patients (1,219 males and 897 females) were on chronic dialysis during the study period by March 31, 1993. Every case of stroke and acute myocardial infarction during the study period was registered. The odds ratio was calculated using the data of the general population in each sex and age class obtained in the same area. A total of 86 cases of stroke and 15 cases of acute myocardial infarction were registered during the study period. The annual incidence, per 1,000 patient-years, of stroke was 12.5 (1988), 10.5 (1989), 12.7 (1990), 14.0 (1991), and 17.5 (1992). The incidence of stroke was increased in the post-erythropoietin period compared to the pre-erythropoietin period, odds ratio 1.22 and 95% confidence interval (95% CI 1.06-1.41, p < 0.01). The annual incidence of acute myocardial infarction was 1.0 (1988), 1.8 (1989), 0.8 (1990), 2.9 (1991) and 4.7 (1992). The incidence of acute myocardial infarction was increased significantly in the post-erythropoietin period compared to the pre-erythropoietin period, odds ratio 1.87 (95% CI 1.66-2.10, p < 0.01). The odds ratio of stroke to the general population was 4.25 (95% CI 3.10-5.82) in the pre-erythropoietin and 4.58 (95% CI 2.14-9.80) in the post-erythropoietin period. In acute myocardial infarction, it was 2.98 (95% CI 2.84-3.12) and 3.81 (95% CI 3.18-4.56). The odds ratio of acute myocardial infarction was significantly increased (p < 0.01). The introduction of erythropoietin was associated with an increased risk of cardiovascular disease, especially acute myocardial infarction. Erythropoietin may unmask the sclerotic lesion in chronic dialysis patients.
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PMID:Increased risk of cardiovascular disease with erythropoietin in chronic dialysis patients. 917 10

To investigate the influence of functioning on unexplained senile anemia, we measured commonly used hematological parameters (serum iron, transferrin, iron saturation and ferritin) in addition to specific erythropoietic factors, such as interleukin-3 (IL-3), interleukin-6 (IL-6), and erythropoietin (EPO) in 48 elderly subjects aged 65-90 years. The subjects were divided into 3 groups: 1) 17 patients with unexplained mild anemia; 2) 17 non-anemic patients with newly acquired stroke and who previously were functionally active; 3) 14 functionally active patients with no major disease who served as controls. Anemia was defined as hemoglobin (Hb) values under 12.0 g/dL. The degree of functional ability was defined and scored by the "functional independence measure" (FIM) test. Data are presented as mean values +/- SD. The results revealed a correlation between the functional state and levels of Hb, iron and transferrin with unchanged iron saturation. Patients in the mild anemia group were found to be functionally declined (FIM = 57 +/- 19.4) with the relatively lowest mean iron (75.1 +/- 17 micrograms/dL) and transferrin levels (243 +/- 42.6 micrograms/dL). The stroke group (FIM = 62 +/- 17.7) had intermediate levels of iron (85.4 +/- 20.3 micrograms/dL) and transferrin (245 +/- 45.2), and with the continuation of the declined functional state the Hb level decreased significantly (13.7 +/- 0.9 to 12.0 +/- 1.0 g/dL, p < 0.001). The highest mean values of iron (102 +/- 27.9 micrograms/dL) and transferrin (322 +/- 42.7 micrograms/dL) were found in the control group (FIM = 122.7 +/- 5.8). The ferritin levels showed an opposite trend. IL-3 values were undetectable in the anemic and control groups, and were elevated in some patients in the stroke group. The lowest IL-6 level was observed in the anemic group, and the highest in the control group. Serial IL-6 assays in the stroke group showed an upward trend. Erythropoietin levels in all groups showed no difference.
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PMID:Relationship between routine hematological parameters, serum IL-3, IL-6 and erythropoietin and mild anemia and degree of function in the elderly. 958 49

Erythropoietin (EPO) prevents the ischemia-induced delayed neuronal death in the hippocampal CA1 field in gerbils. EPO receptor (EPOR) is also expressed in the cerebral cortex but its function is not known. To examine whether EPO has a neuroprotective action in the cortex, EPO was infused into the cerebroventricles of stroke-prone spontaneously hypertensive rats with permanent occlusion of the left middle cerebral artery. Morris water maze test indicated that EPO infusion alleviated the ischemia-induced place navigation disability. The left (ischemic)-to-right (contralateral nonischemic) (L/R) ratio of cerebrocortical area in the EPO-infused ischemic group was larger than that in the vehicle-infused ischemic group. The occlusion caused secondary thalamic degeneration but infusion of EPO prevented the decrease in the L/R ratio of thalamic area and supported neuron survival in the ventroposterior thalamic nucleus. In situ hybridization indicated that EPOR mRNA was upregulated in the periphery (ischemic penumbra) of a cerebrocortical infarct after occlusion of the middle cerebral artery, suggesting that an increased number of EPOR in neurons facilitates the EPO signal transmission, thereby preventing the damaged area from enlarging.
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PMID:Erythropoietin prevents place navigation disability and cortical infarction in rats with permanent occlusion of the middle cerebral artery. 987 14

Target hematocrit/hemoglobin values in dialysis patients are still controversial. The Spanish Cooperative Renal Patients Quality of Life Study Group (including 34 hemodialysis units) conducted a prospective, 6-mo study of the effect on patient functional status and quality of life of using epoetin to achieve normal hematocrit in hemodialysis patients with anemia. The possible adverse effects of increased hematocrit, patient hospitalization, and epoetin requirements were also studied. The study included 156 patients (age range, 18 to 65 yr). Given the minimal experience in the safety of increasing hematocrit in dialysis patients to normal levels with epoetin, stable patients on hemodialysis who had received epoetin treatment for at least 3 mo and had a stable hemoglobin level of > or = 9 g/dl were included in the study. Patients with antecedents of congestive cardiac failure, ischemic cardiopathy, diabetes mellitus, uncontrolled hypertension, cerebrovascular accident or seizures, malfunction of the vascular access or severe comorbidity (defined by a comorbidity index), and those over 65 yr of age were excluded from the study. Quality of life was measured with the Sickness Impact Profile (SIP) and Karnofsky scale. Patients completed questionnaires at home at onset and conclusion of the 6-mo study. Mean hematocrit increased from 30.9 to 38.4% and hemoglobin from 10.2 to 12.5 g/dl during the study. Health indicator scores improved significantly: mean Physical Dimension (SIP) from 5.38 to 4.1 (P < 0.005); mean Psychosocial Dimension from 9.2 to 7 (P < 0.001); mean global SIP from 8.9 to 7.25 (P < 0.001); mean Karnofsky scale score from 75.6 to 78.4 (P < 0.01). (SIP is scaled so that lower scores represent better functional status, and vice versa for the Karnofsky scale). Therefore, functional status and quality of life improved with increased hematocrit. No deaths occurred. Three patients (2%) were censored for hypertension and nine (5.7%) for thrombosis of the vascular access. The cumulative probability of thrombosis of the vascular access was 0.067. The average epoetin dose rose from 93 +/- 62 U/kg per wk at onset to 141 +/- 80 U/kg per wk at conclusion, a 51% increase. The number of patients hospitalized decreased and hospital lengths of stay were shorter during the study period than in the same patients in the 6-mo period preceding the study (P < 0.05). Nine patients (5.7%) had thrombosis of the vascular access. There were no changes in the prevalence of arterial hypertension, but three patients (2%) showed hypertension that was difficult to control. It is concluded that normalization of hematocrit in selected hemodialysis patients, i.e., nondiabetic patients without severe cardiovascular or cerebrovascular comorbidities, improves quality of life and decreases morbidity without significant adverse effects.
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PMID:Increasing the hematocrit has a beneficial effect on quality of life and is safe in selected hemodialysis patients. Spanish Cooperative Renal Patients Quality of Life Study Group of the Spanish Society of Nephrology. 1066 41

Erythropoietin (EPO) is a glycoprotein that has been shown to mediate response to hypoxia, and is most notably recognized for its central role in erythropoiesis. In a series of experiments using rodent models, the ability of systemically administered recombinant human erythropoietin (r-HuEPO, epoetin alfa) to cross the blood-brain barrier and affect the outcome of neuronal injury or cognitive function was evaluated. It was shown that EPO and EPO receptors are expressed at capillaries of the brain-periphery interface, and that systemically administered epoetin alfa crossed the blood-brain barrier. Compared with control animals, epoetin alfa significantly reduced tissue damage in an ischemic stroke model when administered 24 hours before inducing stroke, with significant protection still evident when epoetin alfa was administered 6 hours poststroke. Epoetin alfa reduced injury by blunt trauma when administered 24 hours before trauma, with a significantly smaller volume of tissue necrosis noted when compared with controls. The observation that epoetin alfa may reduce nervous system inflammation was confirmed when an experimental autoimmune encephalomyelitis model in which rats were shown to have significantly delayed onset and reduced severity of experimental autoimmune encephalomyelitis symptoms after treatment with epoetin alfa. Epoetin alfa also was shown to ameliorate the latency and severity of seizures, and significantly increase survival versus controls when exposed to kainate. These findings suggest future potential therapeutic uses for epoetin alfa beyond its current use to increase erythropoiesis.
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PMID:Effects of epoetin alfa on the central nervous system. 1139 56

Erythropoietin (EPO) primarily is produced in the kidney and acts as a principal mediator of the physiologic response to hypoxia by increasing red blood cell production. Astrocytes and neurons in the central nervous system (CNS) also are known to produce EPO in response to hypoxia/ischemia. EPO appears to play a neuroprotective role based on preclinical data demonstrating the ability of recombinant human erythropoietin (r-HuEPO) to shield neurons from hypoxic/ischemic stress when administered intracerebraventricularly. In CNS models, systemically administered r-HuEPO has not been intensely investigated because large glycosylated molecules generally were deemed incapable of crossing the blood-brain barrier (BBB). A collaborative research effort identified expression of EPO receptors on human brain capillaries and a specific receptor-mediated transport of r-HuEPO across the BBB after a single intraperitoneal (IP) injection in rodents, with subsequent protection against various types of neuronal damage. For example, administration of r-HuEPO 24 hours before or up to 6 hours after focal ischemic stroke significantly reduced the extent of infarction. r-HuEPO also attenuated concussive brain injury, kainate-induced seizure activity, and autoimmune encephalomyelitis. These preclinical findings suggest that r-HuEPO may have therapeutic potential for stroke, head trauma, and epilepsy; additional studies are needed to confirm and extend these encouraging observations in animal models.
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PMID:Beyond erythropoiesis: novel applications for recombinant human erythropoietin. 1152 26

In its hormonal role, erythropoietin is produced by the kidney in response to hypoxic stress and signals the bone marrow to increase the number of circulating erythrocytes. It has become clear in recentyears, however, that erythropoietin and its receptor are members of a cytokine superfamily that mediates diverse functions in nonhematopoietic tissues. Nonhormonal erythropoietin actions include a critical role in the development, maintenance, protection, and repair of the central nervous system (CNS). Our group has found serendipitously that recombinant human erythropoietin administered into the systemic circulation is not strictly excluded from the brain. Human recombinant erythropoietin appears within the cerebrospinal fluid in neuroprotective concentrations, probably by translocation initiated by binding to the erythropoietin receptor on the luminal surface of the endothelium. This observation suggested that recombinant human erythropoietin could be therapeutic for CNS diseases, a possibility further supported by positive findings in a model of ischemic stroke. Recombinant human erythropoietin administered systemically either in advance of, or up to 3 hours after, a cerebral arterial occlusion in rats prevents apoptosis of neurons within the ischemic penumbra and reduces infarction volume by 75%. Erythropoietin also dramatically reduces postinfarct inflammation in this model. Other brain and spinal cord injuries such as mechanical trauma, experimental autoimmune encephalitis or subarachnoid hemorrhage also respond favorably to erythropoietin administered within a similar window of time. In addition to ameliorating neuronal injury, erythropoietic therapy also directly modulates neuronal excitability and acts as a trophic factor for neurons in vivo and in vitro. Erythropoietin may therefore provide benefit in epileptic or degenerative neurologic diseases. Given the outstanding safety record for recombinant human erythropoietin after more than a decade in widespread clinical use, the results of multiple preclinical investigations suggest that this cytokine or its derivatives may be useful for treatment of a variety of nervous system diseases.
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PMID:What evidence supports use of erythropoietin as a novel neurotherapeutic? 1238 Sep 58

Erythropoietin (EPO) is an endogenous cytokine with antiapoptotic, antiinflammatory, and neurotrophic properties. Apart from being produced by the kidney, liver, and spleen in response to hypoxia, EPO is highly expressed in the brain during development and after neuropathological insults. The observation that receptors for EPO are present on brain capillaries and glial capillary end-feet has suggested that circulating (plasma) EPO may be transferred into the brain. This review summarizes the increasing number of studies indicating that peripherally administered recombinant human (rHu) EPO crosses the blood-brain barrier. Moreover, several of these studies have shown that peripherally administered rHuEPO can protect against the damage caused by a diversity of neuropathological conditions such as (a) stroke, (b) head and spinal cord trauma, (c) inflammatory and demyelinating conditions, (d) toxin-induced epileptic seizures, and (e) retinal ischemia. While all these studies are based on experiments in animal models, the effectiveness of rHuEPO in ischemic stroke in human patients has recently been suggested in a proof-of-concept trial, which is also discussed.
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PMID:Recombinant human erythropoietin for neuroprotection: what is the evidence? 1253 71


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