Midwest Sickle Cell Center (MSCC)

中西部镰状细胞中心 (MSCC)

• 批准号: 8072115
• 负责人: Cheryl A Hillery
• 金额: $ 68.05万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-06-15 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8072115
• 关键词: Midwest; Sickle; Cell; Center; MSCC

DESCRIPTION (provided by applicant): The Midwest Sickle Cell Center (MSCC) is built upon the longstanding scientific relationship that exists between the multi-disciplinary research sickle cell disease (SCD) teams at the Medical College of Wisconsin and Washington University School of Medicine. The MSCC unites basic research, translational research, clinical outcomes analyses, and excellent comprehensive clinical services to improve the understanding and management of complications of SCD. Inter-Center Project 1 will test the safety and efficacy of the addition of intravenous magnesium to standard therapy for acute vaso-occlusive events in a double-blind, randomized, placebo-controlled trial. While the primary outcomes are safety and length of hospital stay, this Project will also investigate the effect of magnesium therapy on the nitric oxide pathway and endothelial dysfunction, synergizing with Projects 4 and 5. Patient Outcomes Project 3 will develop a pediatric- and SCD-specific health-related quality of life module that will be a critical tool to measure the impact of SCD and effect of treatment from the perspective of the patient. Basic Project 4 will study the role of hemolysis in the altered vascular responses found in human and murine SCD by examining the interplay between nitric oxide, lipid oxidation and cell free hemoglobin. Translational Project 5 will examine the role of cysteinyl leukotrienes and chronic inflammation in the development of SCD pathologies. The basic science component will explore biological mechanisms in both human and murine SCD using the cysteinyl leukotriene receptor inhibitor, montelukast. The clinical portion of Project 5 will conduct a safety trial to assure that montelukast does not increase morbidity (pain) and a feasibility trial to determine if montelukast has the potential to reduce the systemic measures of the inflammatory response. Administrative Core A will provide scientific, fiscal and administrative support for the MSCC. In additional to providing rigorous sate-of-the-art comprehensive care for children and adults with SCD, Clinical Core B will serve as the clinical research infrastructure for human subjects research within all three intra-Center Projects and the planned collaborative inter-Center trials. Patient Services Core C will focus on educational services for patients, families and communities impacted by SCD. Finally, Animal Core D will provide essential services and expertise for the in vivo studies using murine models in Projects 4 and 5.

描述（由申请人提供）： 中西部镰状细胞中心（MSCC）建立在威斯康星州医学院和华盛顿大学医学院的多学科研究镰状细胞病（SCD）团队之间长期存在的科学关系之上。MSCC将基础研究、转化研究、临床结局分析和卓越的综合临床服务结合起来，以提高对SCD并发症的理解和管理。中心间项目1将在一项双盲、随机、安慰剂对照试验中检测在急性血管闭塞事件的标准治疗中添加静脉镁的安全性和有效性。虽然主要结局是安全性和住院时间，但该项目还将研究镁治疗对一氧化氮途径和内皮功能障碍的影响，与项目4和5协同作用。患者结局项目3将开发儿科和SCD特定健康相关生活质量模块，该模块将成为从患者角度衡量SCD影响和治疗效果的关键工具。基本项目4将通过检查一氧化氮、脂质氧化和游离血红蛋白之间的相互作用，研究溶血在人类和小鼠SCD中发现的血管反应改变中的作用。转化项目5将研究半胱氨酰白三烯和慢性炎症在SCD病理发展中的作用。基础科学部分将探索在人类和小鼠SCD使用半胱氨酰白三烯受体抑制剂，孟鲁司特的生物学机制。项目5的临床部分将进行一项安全性试验，以确保孟鲁司特不会增加发病率（疼痛），并进行一项可行性试验，以确定孟鲁司特是否有可能减少炎症反应的全身指标。行政核心A将为MSCC提供科学、财政和行政支持。除了为患有SCD的儿童和成人提供严格的最先进的综合护理外，临床核心B还将作为所有三个中心内项目和计划的合作中心间试验中人类受试者研究的临床研究基础设施。患者服务核心C将专注于为受SCD影响的患者、家庭和社区提供教育服务。最后，Animal Core D将为项目4和项目5中使用小鼠模型的体内研究提供必要的服务和专业知识。

项目成果

Protective effect of HLA-DQB1 alleles against alloimmunization in patients with sickle cell disease.

HLA-DQB1等位基因对镰状细胞疾病患者的保护作用。

• DOI: 10.1016/j.humimm.2015.10.010
• 发表时间: 2016-01
• 期刊: Human immunology
• 影响因子: 2.7
• 作者: Tatari-Calderone Z;Gordish-Dressman H;Fasano R;Riggs M;Fortier C;Campbell AD;Charron D;Gordeuk VR;Luban NLC;Vukmanovic S;Tamouza R
• 通讯作者: Tamouza R

Monitoring toxicity, impact, and adherence of hydroxyurea in children with sickle cell disease.

• DOI: 10.1002/ajh.22101
• 发表时间: 2011-09
• 期刊: AMERICAN JOURNAL OF HEMATOLOGY
• 影响因子: 12.8
• 作者: Brandow, Amanda M.;Panepinto, Julie A.
• 通讯作者: Panepinto, Julie A.

Clinically meaningful interpretation of pediatric health-related quality of life in sickle cell disease.

• DOI: 10.1097/mph.0000000000000177
• 发表时间: 2015-03
• 期刊: Journal of pediatric hematology/oncology
• 作者: Beverung LM;Varni JW;Panepinto JA
• 通讯作者: Panepinto JA

The association of CD81 polymorphisms with alloimmunization in sickle cell disease.

• DOI: 10.1155/2013/937846
• 发表时间: 2013
• 期刊: Clinical & developmental immunology
• 作者: Tatari-Calderone Z;Tamouza R;Le Bouder GP;Dewan R;Luban NL;Lasserre J;Maury J;Lionnet F;Krishnamoorthy R;Girot R;Vukmanovic S
• 通讯作者: Vukmanovic S

Neuropathic pain in patients with sickle cell disease.

• DOI: 10.1002/pbc.24838
• 发表时间: 2014-03
• 期刊: PEDIATRIC BLOOD & CANCER
• 影响因子: 3.2
• 作者: Brandow, Amanda M.;Farley, Rebecca A.;Panepinto, Julie A.
• 通讯作者: Panepinto, Julie A.