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Biomedical subjects

Palle Bekker Jeppesen

Publications and source records attributed to Palle Bekker Jeppesen.

6 recordsLinked to original sources

Short bowel syndrome and intestinal failure: consensus definitions and overview.

Short bowel syndrome (SBS)-associated intestinal failure is a highly disabling condition that impairs quality of life and social integration. Although the condition is not uniformly fatal, it might lead to serious, life-threatening complications. The basic goals of medical treatment are to maintain fluid, electrolyte, and nutrient balances and to make appropriate modifications in disease management to avoid side effects. Various definitions have been proposed for SBS and intestinal failure within the medical literature, but many focus on different aspects of the conditions, leading to confusion. In the past, identifying the cause of intestinal failure was of little consequence, because all patients were managed on total parenteral nutrition at home. However, with the recent development of medical therapies such as recombinant growth hormone, octreotide, and glucagon-like peptide-2 analogues and with improvements in small bowel transplantation, many patients can be made nutritionally autonomous. To evaluate the relative efficacy of these therapies, there is now a need to develop consensus definitions so that patients can be properly categorized before therapy. To this end, a group of experts on the subject was convened to develop the following new definitions: "Intestinal failure results from obstruction, dysmotility, surgical resection, congenital defect, or disease-associated loss of absorption and is characterized by the inability to maintain protein-energy, fluid, electrolyte, or micronutrient balance." "Short-bowel syndrome results from surgical resection, congenital defect, or disease-associated loss of absorption and is characterized by the inability to maintain protein-energy, fluid, electrolyte, or micronutrient balances when on a conventionally accepted, normal diet."

Humans↗

Glucagon-like peptide-2: update of the recent clinical trials.

Although long-term parenteral nutrition is lifesaving in patients with intestinal failure, it is expensive and associated with serious complications such as catheter sepsis, venous occlusions, and liver failure and severely impairs the quality of life in the short bowel patients. Therefore, treatments that increase the absolute intestinal absorption, thereby eliminating or minimizing the need for parenteral support, are needed. In this respect, glucagon-like peptide 2 (GLP-2) has received attention. In this review, the nature of the short bowel syndrome is described, and the antisecretory, transit-modulating, but also intestinotrophic effects of GLP-2 are presented. As illustrated in 2 pilot studies, one using native GLP-2 and the other a degradation-resistant analogue, teduglutide, these new agents may prove important in optimizing remnant intestinal function, thereby eliminating the need for parenteral support and improving quality of life in short bowel patients with intestinal failure.

Adaptation, Physiological↗

Home parenteral nutrition in Denmark in the period from 1996 to 2001.

OBJECTIVE: Home parenteral nutrition (HPN) has been provided to patients with intestinal failure in Denmark since 1970. The results of a national survey comprising a well-defined cohort receiving treatment with HPN in Denmark in the period from 1996 to the end of 2000 are presented, including data on incidence, prevalence, patient characteristics and complications of HPN treatment. MATERIAL AND METHODS: HPN was given to 202 patients (115 F, 87 M) 34% with short-bowel syndrome due to inflammatory bowel disease, 26% with cancer, 22% with surgical complications and 19% with other causes, for a total of 410 catheter years. RESULTS: At the end of 2000, the prevalence of HPN in Denmark was 19.2 per million, and the average annual incidence was 5.0 per million per year over the 5-year period. The incidence rates of catheter-related bacteraemia and thrombosis were 0.48 and 0.02 episodes per catheter year, respectively. The average catheter lasted 1.5 years. Venous inaccessibility was never encountered. The 5-year mortality was 25% (n = 51). However, only six deaths were related to HPN. Three patients died of HPN-related liver failure, two died of catheter-related sepsis and one patient died of an embolus induced by a catheter thrombus. CONCLUSIONS: Since its introduction in 1970 in Denmark, HPN has evolved from an experimental approach to a standardized therapy for patients with intestinal failure. Although HPN morbidity is increasing slightly compared with that reported in earlier surveys, HPN-induced mortality is still less than 1% per year.

Adult↗

The truncated metabolite GLP-2 (3-33) interacts with the GLP-2 receptor as a partial agonist.

The therapeutic potential of the intestinotrophic mediator glucagon-like peptide-2 (1-33) [GLP-2 (1-33)] has increased interest in the pharmacokinetics of the peptide. This study was undertaken to investigate whether the primary degradation product GLP-2 (3-33) interacts with the GLP-2 receptor. Functional (cAMP) and binding in vitro studies were carried out in cells expressing the transfected human GLP-2 receptor. Furthermore, a biologic response of GLP-2 (3-33) was tested in vivo. Mice were allocated to groups treated for 10 days (twice daily) with: (1) 5 microg GLP-2 (1-33), (2) 25 microg GLP-2 (3-33), (3) 5 microg GLP-2 (1-33)+100 microg GLP-2 (3-33), or (4) 5 microg GLP-2 (1-33)+500 microg GLP-2 (3-33). The intestine was investigated for growth changes. GLP-2 (3-33) bound to the GLP-2 receptor with a binding affinity of 7.5% of that of GLP-2 (1-33). cAMP accumulation was stimulated with an efficacy of 15% and a potency more than two orders of magnitude lower than that of GLP-2 (1-33). Increasing doses of GLP-2 (3-33) (10(-7)-10(-5) M) caused a shift to the right in the dose-response curve of GLP-2 (1-33). Treatment of mice with either GLP-2 (1-33) or (3-33) induced significant growth responses in both the small and large intestines, but the response induced by GLP-2 (3-33) was much smaller. Co-administration of 500 microg of GLP-2 (3-33) and 5 microg GLP-2 (1-33) resulted in a growth response that was smaller than that of 5 microg GLP-2 (1-33) alone. Consistent with the observed in vivo activities, our functional studies and binding data indicate that GLP-2 (3-33) acts as a partial agonist with potential competitive antagonistic properties on the GLP-2 receptor.

Animals↗

Enhancing bowel adaptation in short bowel syndrome.

Malabsorption of both nonessential and essential nutrients, fluid, and electrolytes will, if not compensated for by increased intake, lead to diminished body stores and to subclinical and eventually clinical deficiencies. By definition, intestinal failure prevails when parenteral support is necessary to maintain nutritional equilibrium. After intestinal resection, adaptation, a progressive recovery from the malabsorptive disorder, may be seen. Research has focused on optimizing remnant intestinal function through dietary or pharmacologic interventions. In this review, factors responsible for the morphologic and functional changes in the adaptive processes are described. Results of clinical trials employing either growth hormone and glutamine or glucagon-like peptide-2 in short bowel patients are presented.

Adaptation, Physiological↗