INFLUENCE OF RHGH ON INTESTINAL PERMEABILITY IN PATIENTS RECEIVING TPN

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 肠粘膜在维持有效屏障以将管腔菌群排除在生物体内部环境之外方面发挥着重要作用。 在肠衰竭患者中，这种正常的屏障功能可能会因粘膜萎缩和正常管腔菌群的改变而受到损害，从而导致连接蛋白的改变。 此外，屏障功能的改变可能导致肝毒素向门静脉系统的易位增加，从而可能加剧这些患者的肝损伤。 在动物研究中，包括生长激素在内的上皮生长因子已被证明会影响粘膜屏障功能，尽管尚未在人体中进行研究。 我们建议在重组人生长激素（rHGH）治疗前后评估肠衰竭患者的肠道屏障功能和肝损伤。 当小肠（小肠）无法吸收足够的营养物质时，就会导致肠衰竭，尽管它们能够最佳地输送到消化道。 在某些患者中，这是因为他们的肠道太短（短肠综合症，短肠综合症），这通常是由于在之前的手术中被切除而导致的。 在其他情况下，肠道可能很长，但由于其受损（放射性肠炎等）或患病（假性梗阻、克罗恩病等），吸收受到损害。 一般来说，如果整个结肠（大肠、大肠）仍然存在，则需要至少两英尺（60厘米）的功能性小肠；如果没有结肠剩余，则需要三英尺（100厘米）的功能性小肠，才能在没有全胃肠外营养的情况下生存。 乔纳森·弗赖尔 (Jonathan Fryer) 医生自 1995 年来到西北大学以来一直在治疗肠道衰竭患者。西北纪念医院的正式肠道康复计划已实施五年了。 该计划的目标是消除肠衰竭患者对 TPN 的依赖，并最大限度地减少 TPN 无法消除的患者的 TPN 相关并发症。 自该项目启动以来，已有约 100 名患者接受了肠道康复项目的治疗。 这些患者经过仔细筛查，并在适当情况下停止 TPN 治疗。 保守治疗失败的选定患者被考虑进行肠移植。 从历史上看，肠衰竭患者一直接受保守治疗，直到他们因 TPN 治疗而出现继发性终末期肝病，此时他们被转诊进行肝肠联合移植。 通过及早转诊至肠道康复计划，如果 TPN 撤机不成功，可以通过早期撤机和离体肠道移植来预防进展为终末期肝病。 西北纪念医院的肠道康复计划由外科部的 Jonathan P. Fryer 博士和医学部的 Alan Buchman 博士牵头。 肠道康复优化营养、药物和激素疗法以及非移植“肠道延长”手术，以便尽早停止 TPN。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The intestinal mucosa plays an important role in maintaining an effective barrier to exclude the luminal flora from an organism's internal environment. In intestinal failure patients this normal barrier function may be compromised as a result of mucosal atrophy and alterations in the normal luminal flora that can lead to alterations in junctional proteins. Furthermore, altered barrier function may contribute to increased translocation of hepatoxins into the portal system that may exacerbate liver injury in these patients. In animal studies epithelial growth factors, including growth hormone, have been shown to influence mucosal barrier function, although this has not been studied in humans. We propose to evaluate intestinal barrier function and liver injury in intestinal failure patients before and after treatment with recombinant human growth hormone (rHGH). Intestinal failure results when the small intestine (small bowel) is unable to absorb enough of the nutrients despite their optimal delivery to the alimentary tract. In some patients this is because their bowel is too short (short-gut syndrome, short bowel syndrome), which usually results from it being removed during a previous surgery. In others, the bowel may be long but because it is damaged (radiation enteritis, etc.) or diseased (pseudo-obstruction, Crohn's, etc.), absorption is impaired. In general, one needs at least two feet (60cm) of functioning small intestine if the entire colon (large intestines, large bowel) remains, or three feet (100 cm) if there is no colon remaining in order to live without total parenteral nutrition. Dr. Jonathan Fryer has been seeing intestinal failure patients since his arrival to Northwestern in 1995. A formal intestinal rehabilitation program at Northwestern Memorial Hospital has been active for five years. The goals of this program are to eliminate TPN dependency in intestinal failure patients, and minimize TPN related complications in those patients in which TPN cannot be eliminated. Since its inception approximately 100 patients have been seen in the Intestinal Rehabilitation Program. These patients have been carefully screened and if appropriate weaned from their TPN therapy. Selected patients that have failed more conservative management are considered for intestinal transplantation. Historically, intestinal failure patients have been managed conservatively until they have developed end-stage liver disease secondary to their TPN therapy, at which point they were referred for a combined liver and intestine transplant. With early referral to the intestinal rehabilitation program, the progression to end-stage liver disease can be prevented by early weaning from TPN and isolated intestinal transplantation if TPN weaning is unsuccessful. The Intestinal Rehabilitation Program at Northwestern Memorial Hospital is spearheaded by Dr. Jonathan P. Fryer of the Department of Surgery and Dr. Alan Buchman of the Department of Medicine. Intestinal rehabilitation optimizes nutritional, medical, and hormonal therapies as well as non-transplant "gut lengthening" procedures to enable early discontinuation of TPN.