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Query: UMLS:C0032463 (polycythemia vera)
 3,374 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Erythropoietin titers of plasma cannot be used to differentiate polycythemia vera from secondary polycythemia since the limit of sensitivity of our current bioassay technics is 50 mU, considerably higher than levels found in normal subjects and in patients with polycythemia. However, erythropoietin is relatively heat stable, and since abundant plasma is available from therapeutic phlebotomies it is possible to prepare and assay highly concentrated, erythropoietin-containing extracts. In 35 normal subjects, erythropoietin levels ranged from less than 5 mU/ml (the limit of sensitivity) to 18 mU/ml with a mean of 7.8 mU/ml. In 21 patients with proved polycythemia vera, the levels were less than 5 mU/ml in all. In 41 patients with suspected secondary polycythemia or polycythemia of unknown origin, the levels ranged from less than 5 to 3,000 mU/ml. Three of the 11 patients with levels less than 5mU/ml were subsequently shown to have polycythemia vera. These results suggest that this refinement of the routine bioassay for erythropoietin may be of clinical importance in the differential diagnosis of polycythemia.
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PMID:Plasma erythropoietin in polycythemia. 42 68

The effect of renal failure and bilateral nephrectomy on erythropoiesis and plasma erythropoietic activity was observed in a patient with polycythemia vera. For eight years the patient's hematocrit was maintained between 45 and 50 per cent by phlebotomy and in spite of the development of renal failure the hematocrit did not decline. Following rejection of a renal transplant, the hematocrit fell to 18 per cent but rose to 40 per cent with oral iron therapy. Following bilateral nephrectomy, the hematocrit fell to 29 per cent but subsequently increased to 37 per cent. After an episode of gastrointestinal bleeding the hematocrit was 21 per cent but subsequently rose to 32 per cent. Erythropoietin could not be detected in the plasma either before or after nephrectomy. In addition, erythropoietin failed to stimulate 59Fe incorporation into heme in vitro in the patient's marrow cells. The data incidate that, in polycythemia vera, erythropoiesis does not require erythropoietin.
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PMID:Polycythemia vera in an anephric man. 101 15

Three families with polycythemia inherited through apparently different modes are described. Secondary causes of polycythemia were ruled out. Erythropoietin (EPO) levels were normal or low, even after phlebotomy. In vitro erythroid colony growth in standard assay cultures containing EPO was normal; however, in the absence of added EPO, a few progenitors from most of the affected individuals were able to generate recognizable colonies of mature erythroblasts, although these were smaller and proportionately less numerous than seen in polycythemia vera (PV). To search for EPO-receptor changes as a possible pathophysiologic mechanism, we examined, by Southern blot analysis, genomic DNA samples from affected and nonaffected family members, as well as three patients with PV. Two different probes, derived from the human EPO-receptor, were used. We found no evidence for chromosomal rearrangements or gene amplification in hereditary polycythemia or PV patients. Further, no nucleotide sequences were found that were homologous to the Friend spleen focus-forming virus glycoprotein gp55, which has been shown to bind to and activate the murine EPO-receptor. Functional studies examining number and binding affinity of the EPO-receptor on erythroid progenitors from three hereditary polycythemia patients demonstrated no abnormalities. We conclude that the mechanism(s) for the erythrocytosis in familial and congenital polycythemia and in PV may not involve the EPO-receptor and, therefore, may result from alterations of postreceptor responses.
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PMID:Familial and congenital polycythemia in three unrelated families. 131 90

Erythropoietin is a glycoprotein hormone that plays a vital role in erythropoiesis. It is mainly produced in the fetal liver till the third trimester of pregnancy. At that point, the kidney interstitium takes over this function and becomes the main source of erythropoietin. Hypoxia stimulates erythropoietin production by a mechanism that may require a heme protein as a second messenger. Erythropoietin stimulates the maturation of erythroid precursors (colony-forming unit-erythroid and burst-forming unit-erythroid) via at least two types of cell surface receptors. The higher-affinity receptors appear to be more important in modulating the effects of erythropoietin in vivo. Changes in intracellular calcium may ultimately mediate the action of erythropoietin on erythroid precursors. A specific and sensitive radioimmunoassay is now available for accurately measuring erythropoietin levels. All forms of erythrocytosis except polycythemia vera are associated with elevated erythropoietin levels. Levels are also high in cord blood obtained following fetal asphyxia. Reduced levels are seen in patients with anemia due to renal diseases. The response of erythropoietin to the degree of anemia appears to be attenuated in patients with cancer, chronic diseases, and human immunodeficiency virus (HIV) infection. Erythropoietin has been successfully used for treating patients with anemia due to renal failure. Its use has also been approved for the treatment of anemia patients receiving zidovudine for HIV infection. Encouraging results have been observed when erythropoietin was used to treat anemia due to rheumatoid arthritis, hematological malignancies, and prematurity. It has also been used to increase the yield of autologous blood collected prior to an elective surgical procedure. However, it has not proved to be useful in sickle cell anemia and myelodysplastic syndromes.
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PMID:Erythropoietin. Biology and clinical applications. 178 66

Primary polycythaemia (PP), idiopathic myelofibrosis (MF), essential thrombocythaemia (ET) and chronic granulocytic or myeloid leukaemia (CGL) are clonal disorders of the pluripotent haemopoietic stem cells. We have studied granulocyte, megakaryocyte and erythroid progenitors from the peripheral blood of 7 patients with PP, 9 with ET, 19 with MF and 6 with CGL in order to characterise similarities and differences at the committed progenitor cell level. Spontaneous megakaryocytic and erythrocytic growth was characteristic of MF, PP and ET but was not seen in CGL. Circulating erythroid (BFU-E) and granulocyte/macrophage (CFU-GM) progenitors were markedly increased in MF and CGL, less raised in ET and closest to normal in PP. Erythropoietin-independent erythroid bursts (EIBFU-E) grew from the blood of patients with MF, PP and ET but spontaneous growth of megakaryocytes occurred in only MF and ET. These results suggest a progression of increasing abnormality from PP, where EIBFU-E occurred with relatively normal numbers of circulating progenitors, to ET where both EIBFU-E and megakaryocyte precursors regularly occur with elevated numbers of progenitors, to MF where spontaneous BFU-E, CFU-Mk and CFU-GM occur at high levels.
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PMID:Primary polycythaemia, essential thrombocythaemia and myelofibrosis--three facets of a single disease process? 312 58

An autosomal erythrocytosis, inherited as a dominant, occurred in seven members of a family. The propositus was first diagnosed as having erythrocytosis at 26 years of age. He had headaches and marked plethora. Polycythaemia vera and secondary erythrocytosis of known cause were excluded. Erythropoietin level was not elevated. Two of his three children were also found to have erythrocytosis. As in this family, the disease is characterized in middle age by hypertension, cardiovascular and thromboembolic phenomena, as well as abnormal bleeding. For over eight years the propositus has been successfully treated with repeated venous blood lettings.
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PMID:[Idiopathic familial erythrocytosis. Report on a family with autosomal dominant inheritance]. 337 Dec 13

Erythropoietin titers, measured by bioassay of plasma extracts in hypertransfused mice, were determined in 162 patients with absolute erythrocytosis, and the results were correlated with the clinical diagnosis. Fifty-two patients met the diagnostic criteria for polycythemia vera, and all had low or nonmeasurable erythropoietin titers. Of the remaining 110 patients, 62 were suspected clinically as having secondary polycythemia. However, 15 had low erythropoietin titers, casting doubt on the accuracy of the clinical diagnosis. The pathogenesis of the erythrocytosis in the last 48 patients was unknown, and they were designated clinically as having pure erythrocytosis. However, in 20, the erythropoietin titers were increased, and in 28, the titers were low, suggesting that they belonged to at least two different groups. Using erythropoietin titers in the classification of absolute erythrocytosis, the first group should be added to the category of patients with secondary polycythemia as a subgroup with disease due to idiopathic overproduction of erythropoietin (hypererythropoietinemia or essential erythrocytosis). The second group should be added as a subgroup of patients with primary polycythemia under the term erythremia.
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PMID:Pure erythrocytosis classified according to erythropoietin titers. 669 62

Peripheral blood and bone marrow specimens from patients with polycythemia vera (PV) and chronic myelogenous leukemia (CML) were assayed for erythroid and granulopoietic progenitor cells. All compartments were increased in CML patients in relapse although the ratio of BFU-E to CFU-C numbers remained constant in all CML patients where values ranged over several orders of magnitude. By comparison with normal ratios there was only a slight shift towards increased CFU-C numbers. No quantitative changes in any progenitor compartment was found in PV except for a marginal increase in marrow CFU-E. Erythropoietin (epo)-independent colony formation has been documented in all 61 cases of PV studied to date, and the proportion of progenitors classified as abnormal on this basis increases on average 3- to 5-fold as they differentiate in vivo from primitive BFU-E to CFU-E. Preliminary replating studies suggest that when this occurs in vitro individual BFU-E produce both normal and abnormal phenotypes. Epo-independent erythropoiesis has also been commonly observed in assays of CML cells, although its expression is more variable and in the absence of epo progenitors in CML usually make fewer erythroblasts containing even less hemoglobin than do their counterparts in PV. Expression of a common regulatory defect in erythroid cells in PV and CML suggests a possible relationship to the initial transformation event(s).
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PMID:Abnormal erythropoiesis in the myeloproliferative disorders: an analysis of underlying cellular and humoral mechanisms. 696 70

The principal function of erythrocytes is the transport of oxygen. Erythropoiesis proceeds at a rate consistent with the demand for oxygen-carrying capacity, and the major regulator of erythrocyte production is erythropoietin. Erythropoietin is produced primarily by the kidney under control of a tissue oxygenation sensor. The recently developed erythropoietin radioimmunoassay should provide a clinically useful tool. Erythrocytosis is a pathologic state characterized by an elevated erythrocyte mass, which may result from increased proliferation of erythroid progenitors due to an intrinsic cellular defect or in response to extrinsic signals. Secondary erythrocytosis results from either physiologically appropriate compensation for inadequate tissue oxygenation or from inappropriate stimulation of erythropoiesis. Erythrocytosis increases oxygen-carrying capacity of the blood, but at high hematocrit levels increased blood viscosity may result in decreased tissue oxygen delivery. Polycythemia vera is a hematopoietic stem cell disease of clonal origin. Initial results from the Polycythemia Rubra Study Group suggest that therapy with chlorambucil is associated with an unacceptably high risk for development of acute leukemia, and 32P is preferred for situations in which phlebotomy alone is insufficient.
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PMID:Polycythemia: mechanisms and management. 701 37

Erythropoietin is a hormone produced by the kidneys and by certain extrarenal tissues and released into the circulation in response to tissue hypoxia. Its study has provided new information about oxygen transport and bone marrow stem cell function and its determination in plasma can give valuable diagnostic clues as to the etiology and pathogenesis of anemias and polycythemias. The various methods used for such measurements are discussed, and it is recommended that the in vivo bioassay in polycythemic mice be utilized until a workable radioimmune assay has been perfected. The results with the use of this in vivo bioassay to measure plasma erythropoietin in patients with uncomplicated anemia, aplastic anemia, anemia of renal disease, anemia of chronic inflammatory or neoplastic disorder polycythemia vera, and secondary polycythemia are charted and their diagnostic significance discussed.
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PMID:Plasma erythropoietin in health and disease. 739 90


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