Downregulation of epithelial apoptosis and barrier repair in active Crohn's disease by tumour necrosis factor alpha antibody treatment.

BACKGROUND AND AIMS: Barrier dysfunction is an important feature contributing to inflammation and diarrhoea in Crohn's disease (CD). Recently, tumour necrosis factor alpha (TNF-alpha) antibodies were recognised as effective in steroid refractory CD. The aim of this study was to characterise the effects of this therapy on the epithelial barrier. PATIENTS AND METHODS: Forceps biopsies were obtained from the sigmoid colon before and 14 days after TNF-alpha antibody therapy in 11 patients treated for chronic active CD (Crohn's disease activity index >150). Epithelial apoptoses were measured after terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end labelling (TUNEL) and 4',6-diamidino-2-phenylindole staining. Epithelial resistance was determined by alternating current impedance analysis in miniaturised Ussing chambers. Occludin, claudin 1, and claudin 4 expression was quantified in immunoblots. RESULTS: The epithelial apoptotic ratio was 2.1 (0.2)% in controls and increased to 5.3 (1.0)% in CD. TNF-alpha antibody therapy decreased the apoptotic ratio to 2.9 (1.0)% (normalised in 10 of 11 patients). In parallel, epithelial resistance was lower in CD than in controls (24 (3) v 42 (3) Omegaxcm(2)) and improved to 34 (3) Omegaxcm(2) after therapy. Occludin, claudin 1, and claudin 4 were not affected by TNF-alpha antibody therapy. In support of a functional role of epithelial apoptoses in CD, a similar decrease in resistance of -40% was observed when the apoptotic rate was selectively upregulated from 2.6% to 5.4% with camptothecin in HT-29/B6 cells. CONCLUSIONS: Epithelial apoptoses were upregulated in the colon in CD and restored to normal in 10 of 11 patients by TNF-alpha antibody therapy. This is the structural correlate of epithelial barrier dysfunction measured as epithelial resistance while expression of tight junction proteins did not contribute to this therapeutic effect.

[Appendectomy reduces the risk of development of ulcerative colitis]. / Appendektomie senkt Kolitisrisiko.

The etiology and pathogenesis of ulcerative colitis are still unclear. There is, however, a growing consensus that the disease is characterized by a complex interaction between genetic and environmental influences. Many studies in the last few years have suggested that appendectomy reduces the risk of development and improves the course of ulcerative colitis. The underlying mechanism of this effect is unknown. The appendix seems to play a more important role in the development and modulation of the mucosal immune system than believed so far.

Body composition changes in marrow transplant recipients receiving total parenteral nutrition.

Nine patients with acute lymphocytic leukemia in remission, aged 12-35 years, undergoing allogeneic bone marrow transplantation (BMT) were studied for changes in body fluid balance and body composition. Body composition and fluids were assessed the first 4 weeks following BMT, using isotope dilution and anthropometry. Oral and parenteral nutrient intakes were recorded daily. Tracer dilution techniques were used to assess body fluid volumes and estimate body cell, lean body, and body fat masses. Body cell mass was lost (mean -1.62 kg, P less than 0.05) without significant changes in body fat or lean body masses. There was an expansion of the extracellular fluid compartment (mean +0.8 l, P less than 0.05) and a loss in the intracellular fluid compartment (mean -1.3 l, P less than 0.05) with little change in total body water volume. Changes in body weight correlated poorly with body cell mass or fluid volume changes. Change in arm muscle area correlated well with changes in body cell mass (r = 0.61, P less than 0.05) and lean body mass (r = 0.68, P less than 0.05), while that of arm fat area did not reflect its isotope dilution-derived counterpart. Instead, the change in arm fat area was related to shifts in fluid compartments. Prealbumin decreased significantly (mean -9.3 mg/dl, P less than 0.05), while albumin decreased slightly (mean -0.1 mg/dl), and both were related to changes in body cell mass. Nitrogen balance was negative throughout the study and the overall mean was related to the change in body cell mass (r = 0.60, P less than 0.05). Calorie and protein intakes were not associated with the changes in body composition, implying other causal factors.

Effects of resistive exercise on skeletal muscle in marrow transplant recipients receiving total parenteral nutrition.

Skeletal muscle protein loss occurs during marrow transplantation despite total parenteral nutrition. To determine if muscle atrophy could be minimized with exercise therapy, 30 patients undergoing marrow transplantation for acute leukemia completed a prospective randomized trial to receive: (1) no therapy (controls), (2) physical therapy thrice weekly (PT3), or (3) physical therapy five times weekly (PT5). Patients were studied through 35 days posttransplant. Muscle protein status and turnover was assessed by weekly nitrogen balance, and creatinine and 3-methylhistidine excretion. Results favored a muscle protein-sparing effect of exercise, as a significant decrease in creatinine excretion in controls only suggested muscle protein loss associated with inactivity. Changes in arm muscle area correlated with energy, but not protein intake. Large individual variation, inadequate nutritional support and differences in admission arm muscle area may have clouded these results.

Visceral protein status of patients hospitalized for alcoholism.

The purpose of this study was to evaluate the nutritional status of patients hospitalized for alcoholic rehabilitation. It was hypothesized that thyroxine-binding prealbumin, due to its shorter half-life, would be more sensitive to poor nutritional status than other visceral proteins. Extensive biochemical, anthropometric, and nutrient intake data were obtained on hospital days 2, 7, and 14. No abnormalities in visceral protein status initially, or with time, were seen in this population. The principal conclusion is that severe nutritional deficiencies are not prevalent in this patient sample hospitalized for alcoholic rehabilitation.

Implementation of attractive dialogues in nutritive analysis and clinical dietetics information systems.

The implementation and evaluation of a system providing both extensive nutritive-analysis calculations and interactive capabilities are described. The extensive calculating ability of the system arose from the historic need for nutrient intake estimates in clinical investigation and nutritional research. The availability of computer-aided instruction (CAI) system software lead to adoption of the interactive style originating at Ohio State University. Capabilities evolved into an extended interactive processor utilizing an extensive data-base. The interactive processor functions either directly, for immediate response, or as a preprocessor for the more extensive processing system. Use of this capability by a dietetics consortium in the Pacific North-west has lead to definitions of effective and desirable styles of interaction by dietitians with a food and nutrient data-base. Hosting the PILOT CAI language with a high-level language, SAIL, allowed convenient and flexible dialogue creation as well as computational power. The central data-base was restructured on two occasions to accommodate the required characteristics for foods and their nutrients. The lack of interfaces between medical-information packages, and between languages, presently limits the growth of this system into a fully integrated component of the health-care information domain.