INFLUENCE OF RHGH ON INTESTINAL PERMEABILITY IN PATIENTS RECEIVING TPN

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 肠粘膜在维持一种有效的屏障，将腔菌群排除在生物体的内部环境中起着重要作用。在肠衰竭患者中，这种正常的屏障功能可能会因为粘膜萎缩和正常管腔菌群的改变而受到损害，这可能会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移位到门静脉系统的增加，这可能会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经被证明影响粘膜屏障功能，尽管这还没有在人类身上进行研究。我们建议评估肠功能衰竭患者应用重组人生长激素(RhGH)治疗前后的肠屏障功能和肝损伤。 当小肠(小肠)不能吸收足够的营养物质时，就会导致肠道衰竭，尽管这些营养物质最佳地输送到了消化道。在一些患者中，这是因为他们的肠道太短(短肠综合征，短肠综合征)，这通常是由于在以前的手术中将其切除所致。在其他情况下，肠道可能很长，但因为它受到了损害(放射性肠炎等)。或病变(假性梗阻、克罗恩病等)，吸收受损。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)的功能正常的小肠；如果没有剩余的结肠，则需要至少三英尺(100厘米)的功能，才能在没有完全肠外营养的情况下生存。 乔纳森·弗莱尔博士自1995年来到西北大学以来，一直在为肠衰竭患者看病。西北纪念医院的一项正式的肠道康复计划已经活跃了五年。该计划的目标是消除肠衰竭患者对TPN的依赖，并将无法消除TPN的患者的TPN相关并发症降至最低。自开始以来，大约有100名患者参加了肠道康复计划。这些患者都经过了仔细的筛查，并在适当的情况下停止了TPN治疗。选择保守治疗失败的患者考虑进行肠道移植。从历史上看，肠衰竭患者一直被保守治疗，直到他们发展为继发于TPN治疗的终末期肝病，此时他们被转诊为肝脏和肠道联合移植。通过早期转介到肠道康复计划，如果TPN脱机不成功，可以通过早期脱机TPN和隔离肠道移植来防止进展为终末期肝病。西北纪念医院的肠道康复计划由外科的乔纳森·P·弗莱尔博士和内科的艾伦·布赫曼博士带头开展。肠道康复优化了营养、医疗和激素治疗以及非移植“肠道延长”程序，使TPN能够及早停止。

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.