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Query: UMLS:C0728731 (prematurity)
 7,134 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

In order to maintain adequate circulating numbers of blood cells, the bone marrow must produce billions of cells each day and must be able to rapidly increase production by 10-20-fold in response to infection and hemorrhage. The existence of circulating factors that regulate this process has been suspected for over 100 years. Recently, the genes encoding these growth factors were cloned and their functions are now identified. Interleukin-3 (IL-3) acts on the most primitive hematopoietic stem cell, driving this self-renewing cell to produce progeny of all hematopoietic lineages. Granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates the granulocyte-macrophage progenitor cell, as well as cells committed to the erythroid lineage, to differentiate. G-CSF and M-CSF stimulate the most differentiated myeloid progenitors to produce granulocytes and monocytes/macrophages, respectively. Erythropoietin stimulates the differentiation of late erythroid progenitors. In the lymphoid progenitor lineage, IL-2 stimulates T cell differentiation; IL-4 and IL-6 stimulate differentiation of B cells. The colony-stimulating factors also enhance function and cause activation of the mature cells whose production they induce. In clinical trials, these hormones have successfully ameliorated anemia in renal failure, chronic disease, and in prematurity. They have improved pancytopenias in aplastic anemia, myelodysplastic syndromes, and congenital cytopenias, and they have hastened recovery from chemotherapy and bone marrow transplantation.
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PMID:Hematopoietic hormones: from cloning to clinic. 267 59

The purpose of this study was to determine whether an inappropriately low erythropoietin response in premature infants might be a basis for the anemia of prematurity. Erythropoietin was measured by radioimmunoassay in conjunction with hemoglobin and reticulocyte count in untransfused premature infants between birth and 60 days of age. The 27 infants had a mean gestational age of 31 weeks and a mean birth weight of 1378 gm. Between 2 and 30 days, mean erythropoietin concentration was 9.7 mU/ml, significantly and substantially lower than 15.2 mU/ml in 15 concurrently studied healthy adults (P less than 0.01). Subsequently, from 30 to 60 days, values rose gradually to a mean of 17.2 mU/ml, which did not differ significantly from the mean value in adults. Hemoglobin values fell from a mean of 12.9 gm/dl during the first month to 9.0 gm/dl between 30 and 60 days. Thus, during the second postnatal month, preterm infants had essentially the same erythropoietin values as in adults despite a mean hemoglobin concentration that averaged less than two thirds the adult value. This failure to mount a greater erythropoietin response may help to explain why hemoglobin declines to such low values at 2 months of age.
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PMID:Postnatal changes in erythropoietin levels in untransfused premature infants. 619 81

This study was undertaken to determine the factors that are important in determining the erythropoietin response in low-birth-weight infants during the period of so-called anemia of prematurity. In the first weeks of life oxygen consumption in a group of 21 infants gradually increased as hemoglobin level fell. The magnitude of the erythropoietin response inversely varied with the central venous oxygen tension (P-vO2) (r = -0.55, P less than 0.001). When the P-vO2 declined to less than 30 torr, erythropoietin values were uniformly increased above the "normal" range (defined as the values associated with P-vO2 greater than 38 torr). Erythropoietin values varied inversely with hemoglobin but in general did not exceed the values observed for normal adult men. The erythropoietin values in the infants were remarkably lower at any given hemoglobin level when compared with those of older children with anemia resulting from bone marrow failure. In general, elevations of erythropoietin were seen when the hemoglobin concentration declined to less than 10.0 gm/dl. Change in heart rate did not appear to be a reliable indicator of the presence of anemia; rather, it correlated best with oxygen consumption.
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PMID:Anemia of prematurity: determinants of the erythropoietin response. 650 12

Erythropoietin, hemoglobin, hematocrit, oxygen affinity (P50), and reticulocyte counts were measured weekly starting at 1 week of age in 10 very-low-birth-weight infants and on a single occasion in 15 healthy men. In the adults, "available oxygen" (derived from oxygen carrying capacity and P50) averaged 13.1 ml/dl blood and the mean erythropoietin level was 15.2 mU/ml. Erythropoietin levels in the infants were inversely related to concentration of hemoglobin, P50, and available oxygen. However, despite the much lower mean "available oxygen" of 9.3 ml/dl in the infants compared with that in adults (P less than 0.001), the mean erythropoietin value of 8.2 mU/ml in the infants was less than in adults (P less than 0.001). Furthermore, the erythropoietin response to decreased "available oxygen" was lowest in the least mature infants. VLBW infants often develop clinical evidence of hypoxia during the anemia of prematurity. The relatively low erythropoietin levels in relation to "available oxygen" are compatible with a decreased erythropoietin response to hypoxia compared with that in adults. Such a difference in response could be a contributing factor to the anemia of prematurity.
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PMID:Decreased response of plasma immunoreactive erythropoietin to "available oxygen" in anemia of prematurity. 650 13

Increased fetal Hb (HbF) synthesis has been shown to occur during fetal hypoxemia and severe anemia. To determine whether increased HbF synthesis occurs during anemia of prematurity, the levels of HbF synthesis were correlated with the degree of anemia and plasma erythropoietin levels. Thirteen newborn infants born at 29.2 +/- 1.7 wk of gestation were studied at a postconceptional age 36.0 +/- 1.1 wk. Hb levels ranged from 65 to 78 g/L. Blood samples were incubated in an amino acid mixture containing [3H]leucine and chromatographed allowing the separation and quantitation of the alpha, beta, and gamma (A gamma T, G gamma, and A gamma I) chains. Erythropoietin was determined by RIA. The mean HbF synthesis was 77.9 +/- 8.9% of total Hb synthesis (range: 61 to 91%). Plasma erythropoietin concentrations were 21.4 +/- 6.4 mU/mL. There was no correlation between the total Hb or HbF synthesis and the level of erythropoietin. There was, however, a significant inverse correlation between the Hb level and HbF synthesis (p < 0.01). Nine infants who had received transfusions during the first few days of life had a mean HbF that was 53.5 +/- 15.2% of total Hb, whereas their HbF synthesis was 78.4 +/- 7.6%. Four of the infants never received transfusions; the total circulating HbF and HbF synthesis in these infants were 87.7 +/- 7.7% and 76.8 +/- 12.7%, respectively. This study shows that there can be a reactivation of HbF synthesis during severe anemia of prematurity.
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PMID:The reactivation of fetal hemoglobin synthesis during anemia of prematurity. 752 26

Epoetin alfa is a recombinant form of the principal hormone responsible for erythrogenesis, erythropoietin. Already an established treatment for anaemia associated with renal failure, epoetin alfa may also be used to correct anaemia in other patient groups. The drug increases the capacity for autologous blood donation in patients scheduled to undergo surgery and attenuates the decrease in haematocrit often seen in untreated autologous donors. However, transfusion requirements did not significantly decrease in many trials. Epoetin alfa also accelerates red blood cell recovery after allogeneic--but not autologous--bone marrow transplant. Limited data in patients with adult rheumatoid arthritis suggest that while epoetin alfa increases haematocrit/haemoglobin levels, overall clinical rheumatological status may not improve. However, the drug did improve quality of life in a small cohort of children with juvenile rheumatoid arthritis in addition to correcting anaemia. Response rates to treatment with epoetin alfa in patients with anaemia associated with cancer range between 32 and 85%. Anaemia associated with cancer chemotherapy also responds well to treatment with the drug as does anaemia associated with zidovudine therapy in patients with acquired immune deficiency syndrome (AIDS). Studies evaluating the use of epoetin alfa as treatment for anaemia of prematurity have used different methodologies and dosages, making overall analysis difficult. Nevertheless, it appears that high dosages are necessary for response. Results from 1 study suggest that treatment with epoetin alfa appears to be more costly than transfusional support in this application; the relevance of this finding is questionable, however, given that the aim of treatment with epoetin alfa is elimination of transfusion requirements. The incidence of many adverse events associated with epoetin alfa treatment in patients with renal failure (hypertension, seizures and thromboembolic events) has been minimal in patients without renal failure. Adverse events occurred at a similar rate in placebo and epoetin alfa recipients in placebo-controlled trials evaluating the use of the drug as treatment for anaemia in patients with cancer receiving chemotherapy or patients with AIDS receiving zidovudine. In summary, epoetin alfa is an effective alternative to blood transfusion, reducing anaemia and producing consequent improvements in quality of life in many nonrenal applications. It was more effective than placebo in a number of double-blind trials and may be particularly useful as treatment for anaemia associated with other drugs such as cisplatin and zidovudine.
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PMID:Epoetin alfa. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in nonrenal applications. 772 31

Epoetin (recombinant human erythropoietin) is now a widely available though expensive treatment for the anaemia of chronic renal failure, and is effective in more than 95% of patients. Complications of epoetin in this context include hypertension in a third of cases, including hypertensive encephalopathy in a few, and thrombosis of shunts or vascular access devices. Fears that epoetin would cause progression of renal failure have not generally been confirmed, but hyperkalaemia may be a problem in the initial phase of treatment. Epoetin is up to twice as effective when administered subcutaneously rather than intravenously. Responding patients will normally do so within 3 months of starting epoetin. Failures to respond are usually due to iron deficiency or intercurrent disease. Other diseases associated with anaemia and an inappropriately low serum epoetin level include prematurity, the anaemia of cancer and rheumatoid arthritis. The baseline serum endogenous erythropoietin may provide a guide to response in some of these cases. Some encouraging results are being published. Situations where the serum erythropoietin levels are normal or elevated where epoetin has been employed include boosting of haematocrit presurgery as an adjunct to autologous blood donation, treatment of anaemic patients with myelodysplastic syndromes, and improvement of athletic performances.
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PMID:Controversies in selection of epoetin dosages. Issues and answers. 778 87

Erythropoietin (EPO) is a glycoprotein produced primarily by the kidney in response to tissue hypoxia, and is the principal factor regulating red blood cell production. It stimulates erythroid precursors in the bone marrow to proliferate and mature into morphologically identifiable red blood cells. This hormone acts by binding to specific high-affinity receptor on erythroid precursors. Failure to produce adequate quantities of EPO leads to severe anemia, a situation most often encountered in patients with end stage renal disease. With the application of recombinant DNA technology, the gene for this hormone has been molecularly cloned, sequenced and expressed in a biologically active form in mammalian cells. The recombinant EPO has been demonstrated to correct anemia in patients with severe end stage renal disease and alleviate their transfusion requirements. It has also been studied for anemia associated with HIV infection/zidovudine therapy, in cancer, rheumatoid arthritis, and prematurity. In addition it has been studied as a facilitator of autologous blood predeposit in patients scheduled for elective surgery and as a perisurgical adjuvant to hasten hematologic recovery and possibly avoid the need for homologous transfusion after elective surgery. When administered with the current guidelines EPO appears to be safe drug with favorable risk/benefit ratio.
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PMID:[Clinical applications of erythropoietin]. 806 96

The red-cell mass is continuously adjusted to the optimal size for its function as an oxygen carrier by messages transmitted to the bone marrow from an oxygen sensor in the kidney. These messages are mediated by the hormone erythropoietin. Erythropoietin is a glycoprotein growth factor synthesized by cells adjacent to the proximal renal tubule in response to signals from a renal oxygen-sensing device, probably a heme protein (1). In the bone marrow, erythropoietin binds to and activates specific receptors on the erythroid progenitor cells (2). In the presence of this erythropoietin-receptor complex the progenitor cells continue their predestined development into mature erythrocytes. Erythropoietin was the first hemopoietic growth factor to be molecularly cloned in 1985 (3). Our understanding of the biology and physiology of erythropoietin has been considerably improved with the advent of recombinant human erythropoietin (rHuEpo). During the past 7 years, rHuEpo has undergone extensive testing in clinical trials. It has been approved for treatment of the anemia of chronic renal failure, both in progressive renal failure and endstage renal failure (ESRD). In these instances, the administration of rHuEpo has been used in effect as a substitutive therapy, since patients' erythropoietin levels are very low despite severe anemia, due to the failure of affected kidneys to produce adequate amounts of the hormone. However, the application of rHuEpo has now moved largely from the primitive indication of renal diseases, and the hormone is currently under study in a number of anemic states of different etiologies, even with relatively high serum erythropoietin levels. Among these, some of the best documented indications are the anemia associated with malignancies, either due to neoplastic bone marrow infiltration or to chemotherapy-related myelosuppression, the anemia of myelodysplastic syndromes and AIDS, the anemia of chronic inflammatory diseases, prematurity, and bone marrow transplantation (4). The purpose of this review is to provide a summary of our present knowledge regarding rHuEpo therapy for the anemia of renal failure. We provide some clues for the correct use of rHuEpo in the treatment of the anemia of chronic inflammatory diseases. In addition, we address a series of new issues in the attempt to better understand the relationship between erythropoietin and liver disease.
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PMID:Erythropoietin and the anemia of chronic diseases. 840 91


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