INFLUENCE OF RHGH ON INTESTINAL PERMEABILITY IN PATIENTS RECEIVING TPN

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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.