Basic and Translational Research Program

基础和转化研究计划

基本信息

批准号：
7879420
负责人：
THOMAS Duane COATES
金额：
$ 61.31万
依托单位：
CHILDREN'S HOSPITAL OF LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-06-15 至 2013-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7879420
关键词：
Basic Translational Research Program

项目摘要

DESCRIPTION (provided by applicant): Sickle cell disease is characterized by episodes of excruciating pain and chronic organ damage leading to end-organ failure and premature death. In spite of significant improvement in our understanding of the pathophysiology, relatively few advances have been directly translated into treatments that help patients. The fact that the median survival has not improved in the 15 years since the introduction of hydroxyurea, a major treatment advance, suggests that access to expert care is yet another significant poor prognostic indicator for these patients. The overall goal of this program project is to explore avenues of research that are likely to result in new information that can be directly and quickly used in the management of patients with sickle cell disease. To accomplish this, we have assembled a consortium of five medical institutions, three referral groups and the major sickle cell community group all of whom have been working together for many years to care for over 70% of the sickle cell patients in Southern California. The Los Angeles Sickle Cell Consortium (LASCC), including the Sickle Cell Disease Foundation of California will collaborate on five projects that have a direct impact on patient care: 1) we proposed an inter-center project to determine the prevalence of iron overload and its physiologic consequences in adults., 2a) we will examine non-iron related cardiac dysfunction in chronically transfused patients and carry out a novel pilot treatment trial, 2b) we will carry out a randomized pilot study to determine if supplementation with L-glutamine improves exercise tolerance and decreases pain, 3) we will carry out health services research to determine why adult providers don't want to care for sickle patients, what services could be provided by LASCC to facilitate care by adult providers, whether a system we have devised to provide treatment assistance at the point of service is utilized and effective, and whether use of breakthrough technologies can modify care at pilot community emergency rooms or clinics. We will also determine if the treatment proposed in project 2b results in improvement in quality of life and cognitive function, 5) we will directly measure cerebral cortex oxygen delivery, cerebral blood flow, and capillary blood flow in chronically transfused patients and determine the HbS% /viscosity that optimizes these parameters. We will further determine if surrogate markers of sickling that can be measured by non-invasive, clinically applicable techniques are sensitive to changes in HbS% and, in collaboration with project 2b, are improved by supplementation with L-glutamine. This proposal leverages the unique expertise of the Los Angeles team and brings together the skills of investigators from the diverse areas of health services research, engineering, biophysics, cardiology, and nutritional sciences to address critical aspects of sickle cell disease management and delivery of care.

描述（由申请人提供）：镰状细胞疾病的特征是疼痛和慢性器官损害的发作，导致最终器官衰竭和过早死亡。尽管我们对病理生理学的理解有显着改善，但很少有进步直接转化为可以帮助患者的治疗方法。自羟基脲引入以来的15年中，中位生存期（一个重大治疗率）表明，获得专家护理的途径是这些患者的另一个重要的预后指标，这一事实没有得到改善。该计划项目的总体目标是探索可能导致新信息的研究途径，这些信息可以直接，迅速用于镰状细胞疾病的患者的管理。为此，我们组建了一个由五个医疗机构，三个转诊群体和主要的镰状细胞社区组组成的财团，他们已经共同努力了多年，以照顾南加州的70％以上的镰状细胞患者。洛杉矶镰状细胞财团（LASCC），包括加利福尼亚的镰状细胞疾病基金会，将合作从事对患者护理有直接影响的五个项目：1）我们提出了一个中心项目，以确定铁超载及其其普遍存在成人的生理后果。，2a）我们将检查长期输血患者的非铁相关心脏功能障碍，并进行了一项新型的试验治疗试验，2B）我们将进行一项随机的试点研究容忍和减轻疼痛，3）我们将进行卫生服务研究，以确定成年提供者为什么不想照顾镰状患者，LASCC可以提供哪些服务来促进成人提供者的护理，无论我们设计的系统是否已设计为在服务点提供治疗援助是可以利用有效的，以及突破性技术是否可以在飞行员社区急诊室或诊所修改护理。我们还将确定项目2B中提出的治疗是否会改善生活质量和认知功能，5）我们将直接测量长期输血患者的脑皮质氧递送，脑血流量和毛细血管血流，并确定HBS％ /优化这些参数的粘度。我们将进一步确定可以通过非侵入性，临床上适用的技术来衡量的疾病的替代标记对HBS％的变化敏感，并且与项目2B合作，通过补充L-谷氨酰胺来改善。该提案利用洛杉矶团队的独特专业知识，汇集了来自卫生服务研究，工程，生物物理学，心脏病学和营养科学不同领域的调查人员的技能，以解决镰状细胞疾病管理和提供护理的关键方面。