AGING AND THE HUMAN ANTIBODY RESPONSE TO C. DIFFICILE

衰老和人类抗体对艰难梭菌的反应

• 批准号: 6779106
• 负责人: LORRAINE KYNE
• 金额: $ 13.9万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-15 至 2006-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6779106
• 关键词: Clostridium difficile; aging; antibiotics; bactericidal immunity; biomarker; clinical research; clostridial infection; curriculum; diarrhea; disease /disorder proneness /risk; geriatrics; human old age (65+); human subject; medical education; microorganism disease chemotherapy; training

A research program will be undertaken by the applicant, Lorraine Kyne, MD, MPH in the Division of Gerontology at the Beth Israel Deaconess Medical Center (BIDMC). The award will provide five years of mentored training and research enabling her to develop her potential to become an independent clinical investigator focusing on patient-oriented research. Dr Jeanne Y. Wei, Chief of Gerontology at BIDMC, Director of the Division on Aging at Harvard Medical School and Dr. Ciaran P. Kelly, Associate Physician in the Division of Gastroenterology, BIDMC, will serve as mentors. The research component will focus on an important iatrogenic, nosocomial condition which affects predominantly older patients: Clostridium difficile-associated disease (CDAD). As the conventional antibiotic therapy of this condition is associated with a high relapse rate and the emergence of antimicrobial resistance, the long term goals of this project are to develop immunobiological products to prevent or ameliorate disease due to C. difficile and to test their efficacy in intervention studies in 'high risk' older persons. The specific aims of this project are; 1) to identify surrogate markers of immune protection against severe, prolonged or recurrent C. difficile diarrhea for use in future C. difficile active or passive immunization trials; 2) to explore the inter- relationship between the immune response to C. difficile, disease due to C. difficile and aging; and 3) to determine the clinical correlates of CDAD, in order to develop a clinical prediction rule which may be used to identify high risk individuals who may benefit from immunization or other preventative strategies. In addition to this project and scheduled meetings with Drs. Wei and Kelly, this award will include a formal research curriculum, including 1) Research ethics, 2) Clinical epidemiology, 3) Statistical analysis, 4) Clinical trials, 5) Aging research and 5) Laboratory techniques. The very substantial research, educational, and clinical resources of the Harvard Division on Aging and the BIDMC Gerontology and Gastroenterology Divisions will be committed to the applicant to ensure successful attainment of the goals of this award.

申请人 Lorraine Kyne（医学博士、公共卫生硕士）将在贝斯以色列女执事医疗中心 (BIDMC) 老年学部门开展一项研究计划。 该奖项将提供五年的指导培训和研究，使她能够发挥潜力，成为一名专注于以患者为导向的研究的独立临床研究者。 BIDMC 老年学主任、哈佛医学院老龄化科主任 Jeanne Y. Wei 博士和 BIDMC 胃肠科副医师 Ciaran P. Kelly 博士将担任导师。该研究部分将重点关注一种主要影响老年患者的重要医源性院内疾病：艰难梭菌相关疾病（CDAD）。 由于这种疾病的传统抗生素治疗与高复发率和抗菌素耐药性的出现有关，因此该项目的长期目标是开发免疫生物学产品来预防或改善艰难梭菌引起的疾病，并在“高危”老年人的干预研究中测试其疗效。 该项目的具体目标是： 1) 确定针对严重、长期或复发性艰难梭菌腹泻的免疫保护替代标志物，以用于未来艰难梭菌主动或被动免疫试验； 2）探索对艰难梭菌的免疫反应、艰难梭菌引起的疾病与衰老之间的相互关系； 3) 确定 CDAD 的临床相关性，以便制定临床预测规则，该规则可用于识别可能受益于免疫或其他预防策略的高风险个体。除了这个项目和与博士的预定会议之外。 Wei和Kelly表示，该奖项将包括正式的研究课程，包括1）研究伦理，2）临床流行病学，3）统计分析，4）临床试验，5）衰老研究和5）实验室技术。 哈佛老龄化部门以及 BIDMC 老年学和胃肠病学部门的大量研究、教育和临床资源将致力于为申请人提供帮助，以确保成功实现该奖项的目标。