NEONATAL ANEMIA--PATHOPHYSIOLOGY AND TREATMENT

此申请是我们先前计划的竞争性续订 项目赠款(PPG)，题为“新生儿贫血：病理生理学和 续签是基于从研究结果中得出的假设 原始PPG加上新生儿血液学和新生的组织 输血医学。尽管最初的PPG的所有目标都有 已取得进展并报告了进展(出版了512份手稿，7份 已提交审查，15个正在准备中)，重要的是 在PPG环境中继续对新生儿贫血的研究，因为：1)医学 科学还没有全面地理解 新生儿红细胞生成生理学和新生儿红细胞生成的病理生理学 早产儿贫血；2)严重的输血依赖性贫血 仍然是早产儿每天面临的问题--为此 治疗的有效性、毒性和最佳使用没有明确的定义。 我们PPG的主题是优化新生儿贫血的管理- 特别是需要红血的早产儿的严重贫血 细胞(RBC)输注。两个战略目标和八个目标将 满足三个项目和一个核心的要求。优化重组基因的使用 人促红细胞生成素(EPO)治疗新生儿贫血项目#1将 继续研究生理、药代动力学(PK)和 促红细胞生成素的药效学(PD)-利用新的方法 生物素化促红细胞生成素。为了研究铁(Fe)有效性的作用和 蛋白质营养在早产儿贫血病理生理中的作用 并确定他们在治疗和可能预防方面的要求 新生儿贫血，项目2将调查蛋白质和 分级口服铁摄入量对红细胞生成的影响 输血和促红细胞生成素在铁治疗中的疗效和安全性 静脉补铁治疗。要确定Autologous的好处， 胎盘输血中含有成熟红细胞和 造血祖细胞/免疫祖细胞，项目3将研究 延迟性脐带夹闭或等效术式的效果 胎盘血输注对维持新生儿血液和红细胞的作用 体积和造血/免疫发育。核心意志 提供行政、统计和研究支持，并 为所有项目提供生物素化实验室服务。要实现这些目标 目标是，在新领域拥有专业知识的更多调查人员 招聘以补充我们现有的PPG正在进行的努力 一群人。

This application is a competitive renewal of our previous Program Project Grant (PPG) entitled "Neonatal Anemia: Pathophysiology and Treatment." The renewal is based on hypotheses developed from findings of the original PPG plus new tissues arising in neonatal hematology and transfusion medicine. Although all objectives of the original PPG have been achieve with progress reported (512 manuscripts published, 7 submitted for review, and 15 in preparation), it is important to continue studies of neonatal anemia in a PPG setting because: 1) medical science has yet to achieve a comprehensive understanding of the physiology of neonatal erythropoiesis and the pathophysiology of the anemia of prematurity; and 2) severe, transfusion-dependent anemia continues to be a problem faced daily by preterm infants-for which the efficacy, toxicity and optimal use of therapies are not clearly defined. The theme of our PPG is to optimize management of neonatal anemia- particularly, severe anemia in preterm infants that requires red blood cell (RBC) transfusions. Two strategic goals and eight objectives will be met by three projects and a core. To optimize use of recombinant human erythropoietin (EPO) in treating neonatal anemia. Project #1 will continue to investigate the physiology, pharmacokinetics (PK) and pharmacodynamics (PD) of EPO-utilizing novel methods that employ biotinylated EPO. To investigate the role of iron (Fe) availability and protein nutrition in the pathophysiology of the anemia of prematurity and to define their requirements in treating and possibly preventing neonatal anemia, Project #2 will investigate the effect of protein and graded oral Fe intakes on erythropoiesis, the effects of RBC transfusions and EPO on Fe therapy, and the efficacy and safety of intravenous Fe therapy. To determine the benefits of autologous placental blood transfusions containing mature RBCs and hematopoietic/immunologic progenitor cells, Project #3 will study the effects of delayed umbilical cord clamping or the equivalent transfusions of placental blood on maintaining neonatal blood and RBC volumes and hematopoietic/immunological development. The Core will provide administrative, statistical and research support and biotinylation laboratory services to all projects. To accomplish these goals, additional investigators, with expertise in new areas, have been recruited to complement the ongoing efforts of our established PPG group.