Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0728731 (prematurity)
7,134 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To assess the risks and benefits of erythropoietin versus erythrocyte transfusion in the treatment of the anemia of prematurity, we randomly assigned 19 anemic preterm infants (birth weight 988 +/- 227 gm; gestational age 27.6 +/- 1.2 weeks; age 41 +/- 15 days; all values mean +/- SD) to receive either transfusion or subcutaneously administered erythropoietin (200 units/kg every other day for 10 doses). In the 10 erythropoietin recipients, corrected reticulocyte counts increased from 2% +/- 1% to 7% +/- 2% (p less than 0.001) and hematocrits increased from 27% +/- 2% to 30% +/- 4% (p less than 0.05). In the nine infants who underwent transfusion, reticulocyte counts did not increase, but hematocrits increased from 28% +/- 4% to 41% +/- 2% after initial transfusion (p less than 0.001) and had decreased to 34% +/- 5% by day 20. Signs attributed to anemia (tachycardia, apnea with bradycardia, and poor weight gain) declined in both the erythropoietin recipients and those who underwent transfusion. However, five of nine infants who underwent transfusion had symptoms within 10 to 14 days and were given further transfusions. Marrow aspiration performed after 7 to 10 days of treatment showed that infants receiving erythropoietin had greater percentages of erythropoietic precursors (p less than 0.01), greater concentrations of mature erythroid progenitors (p less than 0.001), and higher cycling rates of erythroid progenitors (p less than 0.001). The percentage of mature stored neutrophils in marrow was lower in the erythropoietin group than in the transfusion group, resulting in an inverse myeloid/erythroid ratio (0.5:1 vs 6.2:1; p less than 0.001). After 20 days, absolute blood neutrophil counts were lower in the erythropoietin recipients (1.8 +/- 0.9 x 10(3) cells/microliters) than in the infants who underwent transfusion (3.9 +/- 1.9 x 10(3) cells/microliters; p less than 0.05). Administration of erythropoietin thus stimulated erythropoiesis and relieved signs attributed to anemia; the significance of the relative neutropenia remains to be determined. We conclude that erythropoietin administration offers promise as an alternative to erythrocyte transfusion in neonates with symptomatic anemia of prematurity.
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PMID:Recombinant erythropoietin compared with erythrocyte transfusion in the treatment of anemia of prematurity. 194 87

To study the safety and efficacy of administering human recombinant erythropoietin (rHuEPO) to infants with anaemia of prematurity, a combined phase I/II trial of weekly intravenous injections for 4 weeks was undertaken. We treated 16 infants with 10, 25, 50, 100 or 200 units/kg body weight in groups of two to four patients per dose level. They were all born prematurely (mean gestational age: 29 weeks; range 27-32), had a mean post-natal age of 42 days (range: 25-59) and haemoglobin concentration of 87 g/l (range: 72-94) when treatment was started. Four patients (25%) needed a transfusion during the trial, one at day 7 treated with 10 units/kg and 3 at days 15, 25, 29 with 100 units/kg. In the others, a progressive rise in mean haemoglobin values was seen in each group after 21 days of treatment, without a dose-dependent effect. A positive change in absolute reticulocyte counts with a peak after 7-14 days of therapy was observed with low (25-50 units/kg) but not with higher doses, with a significant difference at day 14 between 25 and 100 units/kg (P less than 0.01). A dose-limiting severe neutropenia (absolute neutrophil count less than 0.5 x 10(9)/l) occurred transiently in five patients, with doses greater than 25 units/kg. No infectious complication and no sign of iron deficiency were observed. Weekly low doses of rHuEPO appear safe, convenient to administer and able to induce a reticulocytic response in infants with anaemia of prematurity. A phase III placebo-controlled trial is needed to confirm these results. Neutropenia associated with rHuEPO administration in infants might be related to their stage of human ontogeny.
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PMID:Weekly intravenous administration of recombinant human erythropoietin in infants with the anaemia of prematurity. 195 38

Anemia in the immediate newborn period may be caused by hemolysis, by a failure of red-cell production, or by a combination of both. However, anemia of prematurity often is the result of hemolysis, of a lack of erythropoietin, and/or of nutritional deficits. Transfusion without a search for the cause may obscure the underlying pathology of the anemia. Because severe anemia can be life-threatening, prompt diagnosis and treatment are required. In this article, the fourth of a series of articles on the sequelae of prematurity, a discussion of the pathophysiology, signs and symptoms, data collection, treatment modalities pertinent to the anemia of prematurity, and parental education are discussed.
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PMID:Physiologic sequelae of prematurity: the nurse practitioner's role. Part IV. Anemia. 199 Jan 13

Cloning and expression of the human gene encoding erythropoietin has resulted in the availability of recombinant erythropoietin for clinical and laboratory investigation. Results of such investigations are clarifying the mechanisms that regulate production of erythropoietin in health and disease. It seems likely that erythropoietin administration will reduce, if not replace, erythrocyte transfusions for certain pediatric patients. Those with the anemia of end-state renal disease and anemia of prematurity may be most likely to benefit. Clearly, additional well-controlled studies to assess the risks and benefits of erythropoietin administration will be needed prior to widespread usage of erythropoietin for anemic children.
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PMID:Recombinant erythropoietin. 200 27

Experimental and clinical data implicate inadequate erythropoietin production as an important reason that infants acquire this anemia and suggest that recombinant human erythropoietin (r-HuEPO) might be used to treat or prevent it. We therefore randomly assigned 20 small premature infants (birth weight less than or equal to 1250 gm) who were highly likely to require erythrocyte transfusions for anemia of prematurity to receive 6 weeks of treatment with either intravenously administered r-HuEPO (at a dose of 100 units/kg twice each week) or a placebo. Hematologic measurements, transfusion requirements, and growth were followed during therapy and for 6 months thereafter. Treated (EPO) and control babies did not differ with respect to weight, hematocrit, overall mean absolute reticulocyte count, calculated erythrocyte mass, or rate of growth. However, reticulocyte counts increased earlier in patients given r-HuEPO. Six of ten babies in the EPO group, and 8 of 10 assigned to the control group, received at least one erythrocyte transfusion during treatment. For all infants the amount of blood sampled for laboratory tests was strongly predictive of the volume of packed erythrocytes transfused (r = 0.890; p = 0.0001). Of nine infants who had less than 20 ml packed erythrocytes removed for laboratory tests, none of four given r-HuEPO received a transfusion, whereas three of five infants assigned to the placebo group received one. No toxic effects were attributable to r-HuEPO, and no significant changes in leukocyte or platelet counts occurred during treatment. Reticulocyte counts were correlated with simultaneous platelet counts and were inversely related to absolute neutrophil counts in both study groups. We conclude that r-HuEPO administration is safe and feasible at the dose studied. Additional controlled trials utilizing higher doses of r-HuEPO and larger numbers of patients are justified.
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PMID:Recombinant human erythropoietin in the anemia of prematurity: results of a placebo-controlled pilot study. 155 15

Recombinant human erythropoietin (r-HuEPO) is of interest to pediatric hematologists and neonatologists because it may prove to be an effective alternative to blood transfusions in preventing and treating anemia in premature infants. The anemia of prematurity is the most promising setting for initial clinical trials. However, it is conceivable that recombinant erythropoietin will be given at birth to low-birth-weight infants in an effort to stimulate endogenous erythropoiesis and thereby prevent some of the erythrocyte transfusions required to replace blood sampled for laboratory tests. Beyond its appeal as a therapeutic alternative to red blood cell transfusions, recombinant human erythropoietin is likely to be the first member of an entirely new class of drugs to be used widely in neonatal medicine. These are drugs produced by cloning normal human genes and expressing them in the laboratory. Because many of the problems of premature birth are caused by developmental immaturity, transiently replacing crucial proteins with exact copies produced by the techniques of recombinant DNA technology is an approach that may have a major impact on morbidity and mortality of neonates. Carefully designed, controlled clinical trials will be essential to determine the role of new agents like r-HuEPO in the treatment of medical problems of premature infants.
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PMID:Anemia of prematurity: progress and prospects. 217 57

Recombinant human erythropoietin represents a potential therapeutic alternative to red blood cell transfusions in a number of pediatric anemias. It is effective in correcting anemia associated with chronic renal failure and may significantly reduce the morbidity associated with childhood CRF. Most exposures to allogeneic blood products in pediatrics for treatment of anemia with blood transfusions occur in neonatal intensive care units. If proven effective in treating anemia in premature babies, r-HuEPO will be responsible for a major reduction in the use of blood transfusions in clinical neonatology. Carefully designed, placebo-controlled clinical trials will be required to establish the role of r-HuEPO in anemia of prematurity. Recombinant human erythropoietin also may be useful to increase the amount of blood that can be collected before elective surgical procedures. Another potential indication is to raise the hematocrits of infants with large intracardiac shunts who develop congestive heart failure coincident with the developmental fall in hemoglobin concentration after birth. Finally, r-HuEPO may one day play a role in modifying the expression of globin genes and, thereby, ameliorate the course of sickle cell disease and beta thalassemia. Many questions surrounding the use of r-HuEPO in infancy and childhood are being addressed in ongoing clinical trials.
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PMID:Recombinant erythropoietin in pediatrics: a clinical perspective. 218 91

We reviewed erythrocyte transfusions, given after 2 weeks of age to premature infants, to derive patient selection criteria for trials of administration of recombinant human erythropoietin to maintain hematocrit during the anemia of prematurity. We first studied 122 infants, less than 36 weeks of gestational age, who remained in a level 3 nursery longer than 4 weeks. Multiple logistic regression analysis was used to select those variables associated with more than two transfusions after the second week; these included gestational age, 5-minute Apgar score, transfusion during the first week, and patent ductus ligation. The best predictor, alone or combined, was gestational age less than 30 weeks. This predictor was applied to a second population of 44 premature infants from a level 2 nursery, and we found a 94% probability of excluding those infants who did not receive a transfusion. This information will allow selection of premature infants who are candidates for administration of recombinant human erythropoietin.
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PMID:Prediction of the need for transfusion during anemia of prematurity. 218 13

The remarkable capacity of the bone marrow to compensate for blood loss and for reduced atmospheric oxygen tension has been found to be mediated by a renal hormone, named erythropoietin. It is produced by peritubular interstitial cells in response to renal hypoxia, but molecular engineering has permitted large scale production of an identical recombinant erythropoietin in vitro. When used as a replacement hormone in patients with impaired endogenous production it has been found to be capable of improving or eliminating the anemia of chronic kidney disease and the anemia of prematurity. In the future it may also be used as a pharmacologic agent and possibly be able to control the anemia of patients with bone marrow failure and make them transfusion-independent.
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PMID:Erythropoietin. 220 20

We studied erythropoiesis in infants with the anemia of prematurity by counting the number of colonies derived from erythroid burst-forming units (BFU-E) in the blood of 11 premature infants before they received transfusions. Colony growth in blood from the infants was compared with growth in blood from adults and umbilical-cord blood from term infants, in the presence of erythropoietin, 0 to 2000 mU per milliliter. Addition of increasing concentrations of erythropoietin resulted in a stepwise increase in the number of colonies derived from BFU-E (P less than 0.0005) of all three groups of subjects. Cultures stimulated with 2000 mU of erythropoietin yielded 28.1 +/- 7.6, 88.0 +/- 19.4, and 121.0 +/- 22.5 bursts (mean +/- SE) per 10(5) cells plated in blood from adults, blood from premature infants, and cord blood, respectively. Although more BFU-E-derived colonies appeared when 200 or 2000 mU were present per milliliter in cultures of the infants' blood and cord blood, the intrinsic responsiveness of BFU-E to erythropoietin was similar in all groups. Although the mean hematocrit was 26 percent, mean serum erythropoietin concentrations (+/- SD) in the infants (20.7 +/- 10.0 mU per milliliter) were not significantly different from those in the adult controls (24.0 +/- 6.5). We conclude that progenitor cells committed to erythroid differentiation are present during the anemia of prematurity, and that the intrinsic responsiveness of the circulating BFU-E pool to erythropoietin is normal. These results implicate inadequate production of erythropoietin as the cause of the anemia of prematurity and suggest that recombinant erythropoietin might provide a therapeutic alternative to transfusion for symptomatic babies with this condition.
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PMID:Circulating erythroid progenitors in the anemia of prematurity. 362 81


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