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)

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

To investigate the importance of transfusion practice with packed red cells (PRCs) in premature infants and to identify risk factors significant influencing transfusion practice, we analyzed 75 preterm infants (gestational age: 31 +/- 2 weeks; birth weight: 1459 +/- 402 g) admitted to the neonatal intensive care unit of Catholic University of Rome. Fifty-three (70.7%) of the infants received one or more PRCs transfusions (in total 246 transfusions). The variables associated with an increase in number and frequency of PRCs transfusions were: a) gestational age < or = 30 weeks; b) birth weight < or = 1000 g; c) severe neonatal pathology (ie a respiratory disease requiring ventilatory support and/or a clearly documented or suspected sepsis). Repeated PRCs transfusions during the first week of life significantly (p < 0.01) influenced the need for late transfusions, after 4 weeks of age, for the treatment of the anemia of prematurity. These data indicate that preterm infants with a gestational age < or = 30 weeks, a birth weight < 1000 g and a severe respiratory or infectious disease represent natural candidates for administration of recombinant human erythropoietin to reduce the need for late PRCs transfusions.
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PMID:[Anemia of prematurity: risk factors influencing red cell transfusions]. 779 3

Sixteen infants with the anemia of prematurity were randomly assigned to treatment with packed erythrocyte transfusions, recombinant erythropoietin alone, or epo plus recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF). During the treatment period, blood reticulocyte concentrations remained unchanged in those randomly assigned to receive transfusions, but increased significantly in those who received erythropoietin, either alone or in combination with GM-CSF. The magnitude of increase in hematocrit was not greater in those who received erythropoietin plus GM-CSF than in those who received erythropoietin alone. Blood neutrophil concentrations fell in all four infants who received erythropoietin alone, but increased in all who received erythropoietin plus GM-CSF.
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PMID:Pilot study comparing recombinant erythropoietin alone with erythropoietin plus recombinant granulocyte-macrophage colony-stimulating factor for treatment of the anemia of prematurity. 801 92

We determined the effects of anemia of prematurity on myocardial, metabolic, and erythropoietic functions. Twelve anemic (hemoglobin range, 65 to 78 gm/L) infants without symptoms (gestational age, (mean +/- SD) 28 +/- 2 weeks; birth weight, 1178 +/- 326 gm) were studied at a postconceptional age of 35 +/- 1.6 weeks. All measurements were done before and 36 to 48 hours after a transfusion of packed erythrocytes. Cardiac output, heart rate, and myocardial function were assessed. Oxygen consumption, carbon dioxide production, resting energy expenditure, arterial oxygen pressure for 50% hemoglobin saturation, and the concentrations of erythropoietin and 2,3-diphosphoglycerate were also determined. After transfusion, increased hemoglobin level (75 +/- 4 to 150 +/- 16 gm/L) and decreased oxyhemoglobin affinity (20.8 +/- 1.7 to 23.6 +/- 2.1 gm/L; p < 0.05) caused a decrease in plasma erythropoietin concentration (from 21.1 +/- 6.2 to 5.8 +/- 1.5 mU/ml; p < 0.01). There was a decrease in heart rate (from 155 +/- 10 beats/min to 146 +/- 7 beats/min) and cardiac output (from 281 +/- 73 ml/kg per minute to 199 +/- 62 ml/kg per minute; p < 0.05). Myocardial function indexes, weight gain, and metabolic demands were normal before and after transfusion. These results suggest that oxygenation is adequately maintained in symptom-free infants with anemia of prematurity.
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PMID:Myocardial, erythropoietic, and metabolic adaptations to anemia of prematurity. 804 Jul 78

In the human fetus, liver macrophages appear to be the primary source of erythropoietin (Epo). Epo production shifts from the liver to peritubular cells in the kidney sometime during the 3rd trimester. Some preterm infants experience a hyporegenerative anemia that appears to be caused by inadequate Epo production. It is not clear whether this anemia is due to deficient Epo production by liver macrophages or renal peritubular cells. To assess this situation, we measured Epo mRNA and protein in macrophages obtained from cord blood of preterm and term infants and from peripheral blood of adults. Macrophages from preterm infants generated Epo mRNA and protein as effectively as those from term infants and adults. It appears that the anemia of prematurity is not due to defective Epo production by macrophages.
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PMID:Erythropoietin production by macrophages from preterm infants: implications regarding the cause of the anemia of prematurity. 816 50

A previous study demonstrated suppression of erythropoietin production in patients treated with long-term theophylline. This effect could exacerbate anemia of prematurity in neonates receiving this drug for apnea of prematurity. In this pilot project we evaluated the effect of short-term theophylline administration on serum erythropoietin in healthy adults. Six subjects were given a bolus followed by a continuous infusion of theophylline targeted to achieve a serum level of at least 10 micrograms/ml, followed by oral theophylline for 36 hours. Serum erythropoietin and theophylline levels were measured before, during, and after drug infusion. Complete hemograms were performed before and after completion of the infusion. No significant changes in serum erythropoietin levels were seen at any time (F = 1.57, p = 0.12). Hematologic values also remained unaltered. We conclude that short-term administration of theophylline is unlikely to have any effect on serum erythropoietin levels in healthy adults.
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PMID:The effect of short-term administration of theophylline on erythropoietin levels in healthy adults. 819 42

Cytokines play key roles in the control of hemopoiesis and immunity. As they become available in increasing quantities and purity through improved recombinant technology, cytokines hold great clinical promise. This article focuses on recent clinical experience with a wide variety of cytokines. For example, newer uses of recombinant human erythropoietin include treatment of anemia of prematurity, AIDS, and some hemoglobinopathies. The myeloid-stimulating factors have established a niche in the treatment of chemotherapy-induced neutropenias and as an adjunct to bone marrow transplantation. Combinations of cytokines that act at different levels of hemopoietic proliferation are being evaluated for the treatment of other causes of neutropenia and thrombocytopenia and also as biologic response modifiers.
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PMID:The use of cytokines in children. 820 76

At present, nearly all infants with birth weights of < 1 kg receive blood transfusions for treatment of clinical signs of tissue hypoxia resulting from anemia of prematurity. In contrast to the successful use of recombinant human erythropoietin (rhEp) in adults, treatment of anemic neonates with rhEp to stimulate red cell production and reduce the need for transfusions that pose serious infectious and immunologic risk has not been effective. The present study investigates the pharmacodynamics (PD) of endogenous erythropoietin (Ep) in sheep fetuses to determine possible causes for the poor rhEp response in early development. The dynamic relationship between plasma Ep and plasma iron resulting from spontaneous hypoxemic episodes is investigated by PD system analysis. The erythropoietic effect of Ep is measured in terms of the mobilization of plasma iron needed in the production on new erythrocytes. A hysteresis minimization approach is employed to determine the intrinsic PD dose-response relationship (transduction) of Ep. The dose-response relationship shows a well-defined threshold level that has to be exceeded before Ep begins to show a significant effect on plasma iron. It is postulated that the threshold mechanism may serve a useful purpose during early development by reducing the risk of the fetus developing a pathological degree of polycythemia and hyperviscosity in the relatively hypoxemic fetal environment. At the same time, the threshold serves the purpose of providing a needed response to more severe pathologic hypoxemic episodes. The occurrence of anemia during subsequent postnatal life when PaO2 levels increase markedly may be the inevitable, but unfortunate corollary of a continuation of this mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A system approach to pharmacodynamics. Plasma iron mobilization by endogenous erythropoietin in the sheep fetus; evidence of threshold response in spontaneous hypoxemia. 837 18

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

Surfactant administration for respiratory distress syndrome continues to make an impact on neonatal care as large controlled trials are published. Although considered safe, synthetic surfactant administration has been associated with a rare complication in the form of pulmonary hemorrhage. Despite this, significant benefits have been shown. With the approval by the FDA of two surfactant preparations, this treatment is now in widespread use. Although the mortality rate from respiratory distress syndrome and the number of ventilator days are generally decreased, surfactant effect on the incidence of bronchopulmonary dysplasia has been disappointing. Studies of steroid administration for bronchopulmonary dysplasia and steroid side effects have been published in the past year. Steroid use has become widespread for this condition, although many details of its administration and side effects have yet to be worked out. A new area of promise is the use of erythropoietin for anemia of prematurity. Natural historic data on the retinopathy of prematurity have added to our understanding of this condition and have raised new questions on its pathogenesis. Review articles and studies in the area of neonatal encephalopathy stress the need for a more accurate definition of asphyxia and discuss possible prenatal causes of this condition. An extensive review of neonatal jaundice and new recommendations for its treatment in healthy term newborns has been published but remains controversial.
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PMID:Care of the neonate. 842 28


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