INFLUENCE OF RHGH ON INTESTINAL PERMEABILITY IN PATIENTS RECEIVING TPN

RHGH 对接受 TPN 的患者肠道通透性的影响

• 批准号: 7604328
• 负责人: Jonathan P Fryer
• 金额: $ 0.41万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-12-01 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7604328
• 关键词: INFLUENCE; RHGH; INTESTINAL; PERMEABILITY; PATIENTS

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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 肠粘膜在维持有效屏障以将管腔植物群从生物体的内部环境中排除方面起重要作用。 在肠衰竭患者中，由于粘膜萎缩和正常管腔植物群的改变可导致连接蛋白的改变，这种正常屏障功能可能受到损害。 此外，屏障功能的改变可能导致肝毒素转运到门静脉系统的增加，这可能加重这些患者的肝损伤。 在动物研究中，上皮生长因子（包括生长激素）已显示影响粘膜屏障功能，尽管尚未在人类中进行研究。 我们建议评估肠功能衰竭患者治疗前和治疗后的重组人生长激素（rHGH）的肠屏障功能和肝损伤。 当小肠（小肠）无法吸收足够的营养物质时，就会导致肠衰竭，尽管它们被最佳地输送到消化道。 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被切除。 在其他情况下，肠道可能很长，但因为它被损坏（放射性肠炎等）。或患病（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）的功能小肠，或者如果没有结肠，则需要三英尺（100厘米）才能在没有全胃肠外营养的情况下生存。 博士乔纳森·弗赖尔自1995年来到西北大学以来一直在看肠道衰竭患者。 西北纪念医院的一个正式的肠道康复计划已经进行了五年。 该计划的目标是消除肠衰竭患者的TPN依赖性，并尽量减少无法消除TPN的患者的TPN相关并发症。 自成立以来，大约有100名患者参加了肠道康复方案。 对这些患者进行了仔细筛选，并在适当情况下停用TPN治疗。 选择保守治疗失败的患者考虑进行肠移植。 从历史上看，肠衰竭患者一直采用保守治疗，直到他们继发于TPN治疗的终末期肝病，此时他们被转诊接受肝和肠联合移植。 早期转诊至肠道康复计划，可以通过早期撤机和隔离肠移植（如果撤机不成功）来预防终末期肝病的进展。 西北纪念医院的肠道康复计划是由外科的乔纳森·P·弗赖尔博士和内科的艾伦·布赫曼博士领导的。 肠道康复优化了营养、药物和激素治疗以及非移植的“肠道延长”程序，使TPN能够早期停止。