Pathophysiology of Childhood Hemolytic Uremic Syndrome

儿童溶血尿毒症综合征的病理生理学

• 批准号: 6922877
• 负责人: PHILLIP I TARR
• 金额: $ 38.53万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-02-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6922877
• 关键词: Escherichia coli infections; bacterial cytopathogenic effect; beta globulin; child (0-11); comorbidity; complement; disease /disorder model; disease /disorder prevention /control; disease /disorder proneness /risk; early diagnosis; fibrin; genetic polymorphism; genetic susceptibility; hemolytic anemia; host organism interaction; human genetic material tag; human subject; model design /development; molecular pathology; nucleic acid sequence; pathologic process; patient oriented research; pediatrics; renal failure; thrombosis; vascular endothelium

DESCRIPTION (provided by applicant): Escherichia coli O157:H7-associated hemolytic uremic syndrome (HUS) remains a challenging medical problem. Extensive thrombogenesis, with accompanying fibrinolysis inhibition, precede the earliest indications of renal injury. Trends in thrombogenesis moreover predict the severity of ensuing HUS. Presumably, a massive endothelial injury before renal injury leads to HUS. This injury is amenable to study, and, possibly, to the attenuation of its effects. In this grant, the thrombogenic process in infected children will be studied intensively. Specifically, we will test the hypotheses that thrombogenesis clearly precedes renal injury, and that the rate of fibrin formation on initial assessment of E. coli O157:H7 infections is associated with outcome (Aim 1). To further assess the coagulation lesion, we will also test the hypotheses that net interval accumulation of fibrin between the first and second day of observation predicts outcome of this infection, and that time-dependent changes in prothrombotic kinetics underlie the pathophysiologic cascade leading to the development of HUS (Aim 2). We will also use our unique population to test the hypotheses that (a) the degree of activation of the complement system predicts outcome in children with E. coli O157:H7 infection, and (b) one or more factor H gene polymorphisms is associated with this outcome (Aim 3). Finally, because the endothelial cell is likely to be critical in the evolution of HUS, we will test the hypothesis that differences between the concentration of circulating endothelial cells in infected children predict outcome. We shall also test the subsidiary hypothesis that these cells express proteins plausibly related to their in situ injury or activation (Aim 4). A unique network has been assembled to identify children at risk of developing HUS an average of three days before HUS develops. This is an inadequately studied, but absolutely appropriate, model for toxin-related HUS. This network will be amalgamated with investigative expertise in the fields of coagulation assessment, complement pathophysiology and genetics, and endothelial cell biology. The project seeks a more complete understanding of the cascade leading to HUS, and, with this knowledge, the successful interdiction of this process.

描述（由申请人提供）：大肠杆菌O157: h7相关

项目成果

Escherichia coli O157 exposure in Wyoming and Seattle: serologic evidence of rural risk.

怀俄明州和西雅图的大肠杆菌 O157 暴露：农村风险的血清学证据。

• DOI: 10.3201/eid0910.020254
• 发表时间: 2003
• 期刊: Emerging infectious diseases
• 影响因子: 11.8
• 作者: Haack,JasonP;Jelacic,Srdjan;Besser,ThomasE;Weinberger,Edward;Kirk,DonaldJ;McKee,GarryL;Harrison,ShannonM;Musgrave,KarlJ;Miller,Gayle;Price,ThomasH;Tarr,PhilipI
• 通讯作者: Tarr,PhilipI

Comparison of Escherichia coli O157:H7 antigen detection in stool and broth cultures to that in sorbitol-MacConkey agar stool cultures.

粪便和肉汤培养物中大肠杆菌 O157:H7 抗原检测与山梨糖醇-麦康凯琼脂粪便培养物中大肠杆菌 O157:H7 抗原检测的比较。

• DOI: 10.1128/jcm.38.9.3404-3406.2000
• 发表时间: 2000
• 期刊: Journal of clinical microbiology
• 影响因子: 9.4
• 作者: Stapp,JR;Jelacic,S;Yea,YL;Klein,EJ;Fischer,M;Clausen,CR;Qin,X;Swerdlow,DL;Tarr,PI
• 通讯作者: Tarr,PI

Thrombogenic alleles, Escherichia coli O157:H7 infections, and hemolytic uremic syndrome.

血栓形成等位基因、大肠杆菌 O157:H7 感染和溶血性尿毒症综合征。

• DOI: 10.1097/00001721-200106000-00009
• 发表时间: 2001
• 期刊: Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis
• 作者: Sprouse,JT;Wong,CS;Chandler,WL;Williams,GD;Watkins,SL;Tarr,PI
• 通讯作者: Tarr,PI

Platelet-activating factor and Escherichia coliO157:H7 infections.

血小板激活因子和大肠杆菌O157:H7 感染。

• DOI: 10.1007/s00467-002-0970-7
• 发表时间: 2002
• 期刊: Pediatric nephrology (Berlin, Germany)
• 作者: Smith,JodiM;Jones,Falaah;Ciol,MarciaA;Jelacic,Srdjan;Boster,DanielR;Watkins,SandraL;Williams,GlynD;Tarr,PhillipI;HendersonJr,WilliamR
• 通讯作者: HendersonJr,WilliamR