Comprhensive Sickle Cell Center Program Project

综合镰状细胞中心计划项目

• 批准号: 6504663
• 负责人: MARIE J. STUART
• 金额: $ 179.12万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6504663
• 关键词: clinical research; human subject; sickle cell anemia

DESCRIPTION (provided by applicant): The fundamental challenge of sickle cell disease (SCD) is how a point mutation, which changes a single amino acid in a single protein, in a single circulating cell, causes a disease with protean manifestations, and complex and unpredictable clinical symptoms. The Marian Anderson Comprehensive Sickle Cell Center has been using the first few years of life, a physiologically crucial period when infants with SCD manifest high levels of HbF, to longitudinally evaluate whether potentially important relationships exist between HbF and other biologic parameters related to SCD pathophysiology, and has demonstrated important relationships between HbF, fluid phase coagulation and adhesion markers. The proposed continuation of this prospective, longitudinal study of infants and children (3 months to 4 yrs) will provide critical new information on the importance of specific biologic markers as they relate to the pathophysiology of the microvessel occlusive phenomenon. In addition, these longitudinal studies will create a "biologic footprint" as the infant grows, providing a unique look at the temporal sequence of changes in adherence, endothelial, platelet, white cell and hemostatic activation in the infant and young child as the protective effects of HbF decline, and the subject begins to experience the unfolding systemic effects of HbS polymerization including anemia and pain. An additional clinical project not only provides the fundamental information on the pain experienced by these infants and young children needed to make the biologic and physiologic correlates, it also proposes using innovative new technologies to facilitate clinical and research communication between families, investigators, and clinical staff. The utility of these technologies will be further demonstrated in the development and evaluation of a parent-mediated pain management protocol for young children with SCD. An examination of endothelial cell receptors for PS-positive sickle erythrocytes will serve as the Center's basic science study and combines new information obtained by current Center investigators with innovative molecular biology studies assisted by investigators new to the Center. This unique blend of meticulous clinical care and research is highlighted in the collaborative network protocol which proposes a clinical trial comparing hydroxyurea to hydroxyurea and phlebotomy in SC disease using statistical techniques and preliminary data developed from the Center's previous pain studies, and detailed laboratory studies to help understand the pathophysiology of this poorly understood sickle syndrome. Supporting these studies is a clinical core of dedicated staff that also supports the Center's growing patient population, which now includes adult and pediatric patients in Philadelphia, and a virtual Center at the University of Louisville in Kentucky. Rounding out the Center is a patient services core with a focus on translating our state-of-the-art research and patient care into practice through education and community outreach in Pennsylvania and Kentucky.

描述（由申请人提供）： 镰状细胞病 (SCD) 的根本挑战是点突变（它改变单个循环细胞中单个蛋白质中的单个氨基酸）如何导致一种表现千变万化、临床症状复杂且不可预测的疾病。玛丽安·安德森综合镰状细胞中心一直利用生命的最初几年（SCD 婴儿表现出高 HbF 水平的生理关键时期）来纵向评估 HbF 与 SCD 病理生理学相关的其他生物参数之间是否存在潜在的重要关系，并证明了 HbF、液相凝固和粘附标记物之间的重要关系。 拟继续进行的这项针对婴儿和儿童（3 个月至 4 岁）的前瞻性纵向研究将为特定生物标志物的重要性提供重要的新信息，因为它们与微血管闭塞现象的病理生理学相关。 此外，这些纵向研究将在婴儿成长过程中创建“生物足迹”，为婴幼儿的依从性、内皮细胞、血小板、白细胞和止血激活的时间序列变化提供独特的视角，作为保护作用。 HbF 下降，受试者开始经历 HbS 聚合的全身效应，包括贫血和疼痛。 另一个临床项目不仅提供了这些婴儿和幼儿所经历的疼痛的基本信息，以建立生物和生理相关性，还建议使用创新的新技术来促进家庭、研究人员和临床工作人员之间的临床和研究沟通。 这些技术的实用性将在针对 SCD 幼儿的家长介导的疼痛管理方案的开发和评估中得到进一步证明。 对 PS 阳性镰状红细胞的内皮细胞受体的检查将作为该中心的基础科学研究，并将当前中心研究人员获得的新信息与新加入该中心的研究人员协助的创新分子生物学研究相结合。这种细致的临床护理和研究的独特结合在协作网络协议中得到了强调，该协议提出了一项临床试验，使用统计技术和中心以前的疼痛研究开发的初步数据，以及详细的实验室研究，比较羟基脲与羟基脲和静脉切开术在 SC 疾病中的作用，以帮助了解这种人们知之甚少的镰状综合症的病理生理学。支持这些研究的是由专门的工作人员组成的临床核心，他们也支持该中心不断增长的患者群体，其中现在包括费城的成人和儿童患者，以及肯塔基州路易斯维尔大学的虚拟中心。该中心的另一个核心是患者服务核心，重点是通过宾夕法尼亚州和肯塔基州的教育和社区外展，将我们最先进的研究和患者护理转化为实践。