Comprhensive Sickle Cell Center Program Project

镰状细胞病(SCD)的根本挑战是点突变如何改变单一氨基酸 在单个蛋白质中，在单个循环细胞中，导致一种具有多变表现的疾病，并且复杂和 不可预测的临床症状。玛丽安·安德森综合镰刀细胞中心已经使用了最初的几个 生命中的几年，这是SCD婴儿表现出高水平HBF的生理学关键时期，以纵向评估 HbF与SCD相关的其他生物学参数之间是否存在潜在的重要关系 病理生理学，并已证实HBF、液体相凝血和粘连之间的重要关系 记号笔。这项针对婴儿和儿童(3个月至4岁)的前瞻性纵向研究的拟议延续将 提供有关特定生物标记物的重要性的重要新信息，因为它们与糖尿病的病理生理学有关 微血管闭塞现象。此外，这些纵向研究将创造出婴儿时期的生物足迹 生长，提供了一个独特的时间序列的变化的黏附，内皮，血小板，白细胞和 随着HBF对婴幼儿止血活性的保护作用的减弱，受试者开始 体验HBS聚合的全身性影响，包括贫血和疼痛。一个额外的临床项目 不仅提供了有关这些婴幼儿所经历的疼痛的基本信息， 将生物和生理联系起来，还建议使用创新的新技术来促进临床和 研究交流“_L-V”V_I.....I=Igl.ll.lll_.g；，_.-，.o；II.._.g_i_UE_TV；ID，_，cit，_r_UllIrUl_*_1-.1I1；1_，_；1p=L U_UTL_L，IF T=，IV Iutbt，i，，L_ity_v，f t-，h_v=v 4：_=t..=....._.....h....r....t..r...t...lngil=_will hmhwthP.r 在制定和评估父母为幼儿制定和评估疼痛管理方案中展示了这一点 SCD。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，并将当前中心研究人员获得的新信息与创新的分子生物学相结合 由中心新来的调查人员协助进行的研究。这种精心的临床护理和研究的独特结合是 在协作网络协议中突出显示，该协议提出了一项比较羟基脲和羟基尿素的临床试验 在SC病中使用统计技术和从该中心以前的 疼痛研究和详细的实验室研究，以帮助了解这种鲜为人知的镰刀的病理生理学 综合症。支持这些研究的是专职工作人员的临床核心，他们也支持该中心不断增长的患者 人口，现在包括费城的成人和儿科患者，以及费城大学的一个虚拟中心 肯塔基州的路易斯维尔。该中心是一个患者服务核心，专注于将我们最先进的 在宾夕法尼亚州和肯塔基州，通过教育和社区推广，将研究和病人护理付诸实践。

I. > 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 "_L-V"V_I ..... I =Igl.ll.lll._.g;, _.-,.o;II.IV.._.g_I_Ue_tV;Id,_, cit,,_r¿_ _UllIrUl_ *_1-.1I1;1_,_;1P¿=l ¿U__Utl_l, iFF T¿it=,Iv Iutbt,i,,l_ity _v,f t-,h_v=v=v 4:_= t..=....._.....h....r....t..r...t...lngil=_will hmhwthP.r 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' growing patient population, which now includes adult and pediatric patients inPhiladelphia, 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.