Comprhensive Sickle Cell Center Program Project

描述(由申请人提供)： 镰状细胞病(SCD)的根本挑战是点突变如何改变单个循环细胞中单一蛋白质中的单一氨基酸，导致具有千变万化的症状和复杂且不可预测的临床症状的疾病。玛丽安·安德森综合镰刀细胞中心一直在利用生命的最初几年，这是SCD婴儿表现出高水平HBF的生理学关键期，纵向评估HBF与SCD病理生理相关的其他生物学参数是否存在潜在的重要关系，并证明了HBF、液体相凝血和黏附标志物之间的重要关系。这项针对婴幼儿(3个月至4岁)的前瞻性纵向研究的继续进行，将提供有关特定生物标记物的重要性的重要新信息，因为它们与微血管闭塞现象的病理生理学有关。此外，这些纵向研究将在婴儿成长的过程中创造一个“生物足迹”，提供一个独特的视角，观察随着HBF的保护作用减弱，婴儿和幼儿的粘附性、内皮细胞、血小板、白细胞和止血激活的时间顺序的变化，受试者开始经历HBS聚合的全身影响，包括贫血和疼痛。一个额外的临床项目不仅提供了这些婴幼儿经历的疼痛的基本信息，需要建立生物和生理上的联系，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交流。这些技术的效用将在为患有SCD的幼儿开发和评估父母中介的疼痛管理方案中得到进一步证明。PS阳性镰状红细胞的内皮细胞受体检查将作为该中心的基础科学研究，并将现有中心研究人员获得的新信息与创新的分子生物学研究结合起来，由该中心的新研究人员协助进行。这种细致的临床护理和研究的独特结合在合作网络协议中得到了强调，该协议提出了一项临床试验，使用统计技术和从该中心以前的疼痛研究中开发的初步数据来比较羟基尿素和羟基尿素，并在SC疾病中进行静脉切开术，以及详细的实验室研究，以帮助了解这种鲜为人知的镰刀综合征的病理生理学。支持这些研究的是一个由敬业工作人员组成的临床核心，他们还支持该中心不断增长的患者群体，现在包括费城的成人和儿科患者，以及肯塔基州路易斯维尔大学的一个虚拟中心。该中心是一个患者服务核心，专注于通过宾夕法尼亚州和肯塔基州的教育和社区推广将我们最先进的研究和患者护理转化为实践。

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.