Midcareer Investigator Award in Patient-Oriented Resear

以患者为导向的研究中的职业生涯中期研究员奖

• 批准号: 6421504
• 负责人: ROBIN L BREY
• 金额: $ 12.8万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6421504
• 关键词: Mexican Americans; atherosclerosis; autoantibody; behavioral /social science research tag; brain imaging /visualization /scanning; cardiovascular disorder risk; cerebral ischemia /hypoxia; clinical research; cognition disorders; embolism; human subject; mental health epidemiology; myocardial infarction; neurologic manifestations; neuropsychological tests; neuropsychology; pathologic process; patient oriented research; phospholipid inhibitor; racial /ethnic difference; stroke; systemic lupus erythematosus; thrombosis; ultrasonography; vasculitis; vasospasm

DESCRIPTION (provided by the applicant): Systemic lupus erythematosus (SLE) is a systemic inflammatory autoimmune disease that affects predominantly young, minority, pre-menopausal women. Up to 75% of patients with SLE experience some type of nervous system manifestations during their disease course (termed neuropsychiatric lupus or NPSLE). The most common manifestations include cognitive dysfunction, psychiatric disease and stroke, although the full range of NS involvement has not been well characterized. Two major areas of the candidate's research have been the study of 1) clinical and serologic predictors for the development of NPSLE, and 2) immune-mediated thrombosis related to antiphospholipid antibodies (aPL). The major thrust of this proposal will be to expand a strong clinical research program studying NPSLE in a cohort of predominantly Mexican-American SLE patients by 1) determining the frequency of and risk factors for accelerated atherosclerosis in this well-defined cohort and 2) evaluating the frequency and of microembolic signals (MES) by transcranial doppler (TCD) and the relationship between MES and cerebrovascular ischemia and cognitive dysfunction in 2 cohorts of SLE patients (UTHSCSA and Dusseldorf, Germany) with and without aPL. SLE patients are at increased risk for thrombotic events, including both myocardial infarction and stroke. Several NPSLE manifestations may have cerebral ischemia as a common underlying pathophysiologic mechanism, e.g. cognitive dysfunction and stroke. Potential causes of ischemia in SLE include vasospasm, microvascular disease, thrombosis with or without atherosclerosis, and rarely, vasculitis. The frequency of atherosclerosis in SLE, the importance of atherosclerosis in SLE-related stroke risk, or whether there are important genetic or racial influences are unknown. Traditional vascular risk factors, inflammatory, immunological, and treatment-related factors specific to SLE are all likely to be involved. With the support of the Mid-Career Investigator Award, the candidate will work with a multidisciplinary team of established investigators and fellows in the areas of stroke, vascular and brain imaging, immunogenetics, epidemiology, psychiatry and neuropsychology. This collaborative effort will provide very important information regarding prevalence and extent of sub-clinical vascular disease and associated risk factors in SLE. Much will be learned about the relative importance of genetic factors and autoantibodies on vascular disease risk in SLE that is likely to apply to other populations also at increased risk for cerebral ischemia and vascular dementia.

描述（由申请人提供）： 系统性红斑狼疮 (SLE) 是 一种主要影响年轻人的全身性炎症性自身免疫性疾病， 少数民族、绝经前妇女。高达 75% 的 SLE 患者会经历一些 疾病过程中神经系统表现的类型（称为 神经精神性狼疮或 NPSLE）。最常见的表现包括 认知功能障碍、精神疾病和中风，尽管全方位 NS 参与的情况尚未得到很好的表征。的两个主要领域 候选人的研究包括 1) 临床和血清学研究 NPSLE 发展的预测因素，以及 2) 免疫介导的血栓形成 与抗磷脂抗体（aPL）有关。该提案的主要内容 将扩大一个强大的临床研究项目，在队列中研究 NPSLE 主要是墨西哥裔美国 SLE 患者，方法是 1) 确定频率 在这个明确的队列中加速动脉粥样硬化的危险因素 2) 评估微栓塞信号 (MES) 的频率 经颅多普勒（TCD）及MES与脑血管的关系 两组 SLE 患者（UTHSCSA 和 德国杜塞尔多夫）有或没有 aPL。 SLE 患者的风险增加 血栓事件，包括心肌梗塞和中风。一些 NPSLE 表现可能以脑缺血为常见基础 病理生理机制，例如认知功能障碍和中风。潜在的 SLE 缺血的原因包括血管痉挛、微血管疾病、血栓形成 有或没有动脉粥样硬化，很少有血管炎。的频率 SLE 中的动脉粥样硬化，动脉粥样硬化在 SLE 相关中风中的重要性 风险，或者是否存在重要的遗传或​​种族影响尚不清楚。 传统的血管危险因素，炎症、免疫和 SLE 特有的治疗相关因素都可能参与其中。和 在职业生涯中期研究者奖的支持下，候选人将与 由该领域已建立的研究人员和研究员组成的多学科团队 中风、血管和脑成像、免疫遗传学、流行病学、精神病学 和神经心理学。这种合作努力将提供非常重要的 有关亚临床血管疾病的患病率和程度的信息 以及 SLE 的相关危险因素。将会了解到很多有关亲戚的信息 遗传因素和自身抗体对血管疾病风险的重要性 SLE 可能适用于同样面临更高风险的其他人群 脑缺血和血管性痴呆。