PATHOPHYSIOLOGY OF CHILDHOOD HEMOLYTIC UREMIC SYNDROME

描述 大约10%的儿童感染大肠杆菌0157：H7 溶血性尿毒综合征（HUS） 病理生理级联反应 导致胃肠道感染这种志贺菌 对全身血管损伤的认识还不完全。 没有 合适的动物模型，其中肾小球血栓性病变由 志贺毒素肠内或肠外激发，或肠内激发 E. coli 0157：H7或其它志贺菌性大肠杆菌。杆菌 大肠埃希菌0157：H7 感染仍然经常在华盛顿西部的儿童诊断之前， HUS检测，从而确定处于高风险的儿童群体， 会在一周内出现微血管病后遗症 本研究将探讨 这样的儿童，并测定各种选定的循环，尿液和 粪便炎症、血栓形成前、血管活性、遗传和微生物 可能合理地发挥、引发和/或延续 导致溶血尿毒综合征的微血管病变 这些包括细胞因子， 血栓形成因子，纤溶因子，内皮细胞标志物 损伤/活化，花生四烯酸代谢物，循环内毒素 水平、血小板活化因子浓度、宿主细胞表达 抗原、E.大肠杆菌0157：H7和粪便无毒素，和 毒素基因型 除了定义级联前导的元素之外， 肾衰竭的可能性。coli 0157：H7感染， 也可以确定在以下发展HUS的最高风险组 肠道感染E.大肠杆菌0157：H7，从而表明儿童最有可能 从新的治疗策略中获益。

DESCRIPTION Approximately 10% of children with Escherichia coli 0157:H7 infection develop the hemolytic uremic syndrome (HUS). The pathophysiologic cascade leading from gastrointestinal infection with this Shiga-toxigenic organism to systemic vascular injury is incompletely understood. There are no suitable animal models in which glomerular thrombotic lesions result from enteral or parenteral challenge with Shiga-toxin, or enteral challenge with E. coli 0157:H7 or other Shiga-toxigenic E. Coli. Escherichia coli 0157:H7 infection remains frequently diagnosed in western Washington children before HUS ensues, thereby identifying a population of children at high risk of developing microangiopathic sequelae within a week. This study will examine such children, and assay a selected variety of circulating, urinary and fecal inflammatory, prothrombotic, vasoactive, genetic, and microbial factors which could plausibly play, initiate and/or perpetuate microangiopathic abnormalities leading to HUS. These include cytokines, thrombogenic factors, fibrinolytic factors, markers of endothelial cell injury/activation, arachidonic acid metabolites, circulating endotoxin levels, platelet activating factor concentrations, expression of host cell antigens, concentrations of E. coli 0157:H7 and of fecal free toxin, and toxin genotype. In addition to defining the elements of the cascade leading to kidney failure in children with E. coli 0157:H7 infection, this research could also identify the group at highest risk of developing HUS following enteric infection E. coli 0157:H7, thereby suggesting children most likely to benefit from novel therapeutic strategies.