Comparison of enteral nutrition and drug treatment in active Crohn's disease. Results of the European Cooperative Crohn's Disease Study. IV.

This study compared the effect of enteral nutrition as the sole therapy of active Crohn's disease with drug treatment. Patients with active Crohn's disease (Crohn's Disease Activity Index greater than 200) were randomized to receive either enteral nutrition with a liquid oligopeptide diet (n = 55) or a combination of 6-methylprednisolone, 48 mg daily, subsequently tapered, and sulfasalazine, 3 g daily (n = 52). The two groups were not different with respect to age, sex, body weight, location of disease, or treatment before the study. The severity of disease was similar at the beginning of the study in both groups [Crohn's Disease Activity Index (mean +/- SEM), 323 +/- 12 vs. 316 +/- 11]. Remission was defined as a decrease of the initial Crohn's Disease Activity Index by 40% or at least 100 points. Twenty-nine patients in the diet group and 41 patients in the drug group reached remission within 6 weeks of therapy (chi 2 test, P less than 0.01). The median elapsed time to remission was 30.7 days in the diet group compared with 8.2 days in the drug group (Mantel Cox, P less than 0.01). To determine whether one of these treatments was more beneficial for a subgroup of patients, the effectiveness of both treatments was analyzed separately in patients with very severe disease (initial Crohn's Disease Activity Index greater than 300) and less severe disease (initial Crohn's Disease Activity Index less than 300), and in patients with different disease location. However, no influence of initial disease activity or disease location on the effect of either treatment could be shown. These data show that enteral nutrition is less effective than a combination of 6-methylprednisolone and sulfasalazine in treating active Crohn's disease.

Feasibility and effectiveness of a defined-formula diet regimen in treating active Crohn's disease. European Cooperative Crohn's Disease Study III.

In a randomized multicenter trial the efficacy of treatment of active Crohn's disease by means of a liquid defined formula diet (DFD) was tested and compared with a combination of 6-methyl-prednisolone and sulfasalazine. A total of 95 patients participated in the study. By the end of 6 weeks, among 44 patients randomized to drug treatment, 32 showed improvement of the Crohn's disease activity index (CDAI) as compared with 21 of 51 patients receiving oral DFD (p less than 0.05). The proportion of withdrawals in the DFD group (29 of 51) was sevenfold higher than in the drug group (4 of 44). However, most patients (20 of 29) receiving DFD withdrew because of the unpalatability of the liquid diet. Analysis of patients in each group who finished the study showed equal effectiveness of DFD and the drug regimen. In these subsets of patients the CDAI decreased from 280.8 +/- 90.6 to 151.7 +/- 86.5 (DFD) and from 263.7 +/- 86.3 to 129.3 +/- 63.7 (drug), respectively. Improvement of inflammation factors was similar in both groups at the end of the study, although improvement was delayed in the DFD group. In conclusion, our data show a superiority of the drug combination over DFD in the treatment of Crohn's disease under the conditions of this trial. The results do suggest, however, that DFD offers a therapeutic alternative to prednisolone and sulfasalazine in a subgroup of patients, which has to be closer characterized in further studies.

Nitrogen absorption in pancreatectomized patients: protein versus protein hydrolysate as substrate.

To investigate nitrogen absorption in the absence of the pancreas, six patients with total pancreatectomy, all in stable nutritional and metabolic condition, underwent two periods of enteral nutrition identical in all respects except for the nitrogen source. Nitrogen source was either lactalbumin or its hydrolysate. The quantity and quality of calories infused simulated the patient's usual diet, which was a high-protein diet (2.0 +/- 0.4 gm/kg body weight). Pancreatic enzyme replacement therapy was discontinued during each period of enteral nutrition. All patients had greater nitrogen absorption during the enteral nutrition with lactalbumin hydrolysate than that with lactalbumin (91% +/- 2% vs 61% +/- 6% of nitrogen intake, p less than 0.02). Despite this difference in absorption, nitrogen balances during the two periods of enteral nutrition were not significantly different. This appeared to be caused by a urea production rate that was greater during the enteral nutrition with lactalbumin hydrolysate than the rate during that with lactalbumin (26 +/- 1 gm/24 hr vs 16 +/- 3 gm/24 hr, p less than 0.05). Plasma concentrations of amino acids and proteins did not differ significantly during the two treatments. In conclusion, the data suggest that (1) the intestine plays a significant role in protein digestion and that (2) enteral feeding with a protein hydrolysate could eliminate the need for a high-protein diet in patients with pancreatic insufficiency.

[Ambulatory parenteral nutrition in short bowel syndrome: a retrospective study]. / Ambulante parenterale Ernährung bei Kurzdarm-Syndrom. Eine retrospektive Analyse.

Parenteral nutrition via an indwelling central venous catheter was undertaken at home over a total period of 24,747 days in 34 patients with the short-bowel syndrome (of various causes). In some of the patients there developed complete adaptation of the residual intestine so that parenteral nutrition could be terminated. Complications were: infection, thrombosis, pulmonary embolism and metabolic problems. But the method proved to be suitable for improving the quality of life of these patients.

Peptide mixtures for enteral and parenteral nutrition.

This article reviews the work concerning intestinal absorption of amino acids from a mixture of 12 glycyl-dipeptides in human jejunum as well as nutritional efficacy and safety of different dipeptide mixtures as the nitrogen source of total parenteral nutrition in baboons. Using a segmental perfusion technique, amino acid absorption rates were generally greater and less selective from the dipeptide mixture as compared to the corresponding free amino acid mixture. This can only be explained as a result of peptide uptake by a system that has greater transport capacity than amino acid carrier systems, thus minimizing competition among its substrates. To assess the efficacy and safety of dipeptides as substrates for total parenteral nutrition, the effects of intravenous infusion of two different synthetic dipeptide mixtures as well as a dipeptide supplemented free amino acid mixture on a range of parameters of nutrition, metabolism and organ function were investigated. In each experiment the corresponding free amino acid mixtures served as control. In three experiments in baboons with the period of parenteral nutrition being 1 or 4 weeks, respectively, all dipeptides were efficiently utilized, as evidenced by only trace concentrations of dipeptides in plasma and urine. With a dipeptide supplemented amino acid solution as well as with complete dipeptide mixtures serving as the sole source of nitrogen of parenteral solutions, parameters of nutrition, metabolism and organ function were well maintained. No adverse effects of the dipeptides occurred. These experiments provide the information needed for further investigation of dipeptides as a substrate of enteral and parenteral nutrition in man.

Cell-mediated cytotoxicity in hepatitis A virus infection.

We studied cell-mediated cytotoxicity to hepatitis A virus-infected cells in seven patients with acute type A hepatitis and two controls. Skin fibroblast cultures obtained from the skin biopsies of seven patients after acute hepatitis A virus infection and from two persons without history of current or past hepatitis A virus infection were inoculated with hepatitis A virus. Infection of fibroblast cultures always resulted in an inapparent, persistent infection with production and release of infectious hepatitis A virus. Peripheral blood lymphocytes were collected from the same patients at different times after onset of icterus and were stored in liquid nitrogen. Cytolytic activity of peripheral blood lymphocytes was determined by a microcytotoxicity assay using autologous 51Cr-labeled hepatitis A virus-infected and uninfected target cells. Cytotoxic peripheral blood lymphocytes capable of lysing autologous hepatitis A virus-infected skin fibroblasts were detected in all patients with hepatitis A but were not demonstrable in the controls without antibodies against hepatitis A virus. The clinical course of the hepatitis A virus infection was normal in five patients; and in these patients, cytolytic activity of peripheral blood lymphocytes against hepatitis A virus-infected autologous targets peaked 2 to 3 weeks after onset of icterus. A clinically protracted form of the disease with persistent elevation of aminotransferases for at least 5 months after onset was present in two patients. In these cases, the highest cytolytic activity was demonstrated in peripheral blood lymphocytes collected 8 to 12 weeks after onset of icterus.(ABSTRACT TRUNCATED AT 250 WORDS)

Protein nutrition and amino acid metabolism after 4 weeks of total parenteral nutrition with a mixture of 14 dipeptides: serendipitous observations on effects of sepsis in baboons.

We investigated parameters of nutrition, metabolism, and organ function after 4 wk of total parenteral nutrition (TPN) in baboons receiving either dipeptides or amino acids as the nitrogen source. The two groups showed no significant difference with respect to gain in body weight, nitrogen balance, plasma and muscle concentrations of amino acids, plasma concentrations of proteins, and leucine incorporation into muscle protein. All dipeptides were efficiently utilized as evidenced by trace concentrations of dipeptides in plasma and urine; they produced no deleterious effect on the function of liver, kidney, or immune system. Development of infection in several baboons increased urinary excretion of urea nitrogen but had no effect on urinary excretion of dipeptides and amino acids with the single exception of taurine, which was greatly increased. In conclusion, the data show long-term efficacy and safety of the dipeptide mixture as the sole nitrogen source for TPN.

Kinetics and characteristics of absorption from an equimolar mixture of 12 glycyl-dipeptides in human jejunum.

We have investigated rates of dipeptide disappearance during jejunal perfusion with an equimolar mixture of 12 glycyl-dipeptides and compared amino acid absorption rates from this mixture with those from the corresponding free amino acid mixture in healthy volunteers. All dipeptides contained glycine in the N-terminal position, which was designed to favor peptide absorption rather than hydrolysis. At 2 mM concentration there was little difference in disappearance among dipeptides, but at 6 mM there was some selectivity: Gly-Phe and Gly-Met exhibited the fastest, and Gly-Arg and Gly-His the slowest rates of disappearance. However, between these ends of the spectrum there were only modest differences in disappearance among dipeptides (Gly-Ala, Gly-Thr, Gly-Leu, Gly-Ile, Gly-Val, Gly-Lys, Gly-Pro, Gly-Trp). The amino acid absorption rates were generally smaller but more selective from the free amino acid than from the dipeptide mixture. We conclude that (a) the C-terminal amino acid residue influences intestinal assimilation of glycyl-dipeptides and (b) the considerably greater absorption rate of amino acids from the dipeptide than from the amino acid mixture appears to be the result of uptake by a system that has a greater transport capacity than amino acid carrier systems, thus minimizing competition among its substrates.

European Cooperative Crohn's Disease Study (ECCDS): clinical features and natural history.

In the European Cooperative Crohn's Disease Study patients from 14 centers were included in whom diagnosis was made within 2 years before study entry on the basis of generally accepted radiological, endoscopical and/or histological criteria or a combination of all. Reasons for exclusion were: diagnosis older than 2 years in patients who did not require active treatment, age less than 18 years, duration of symptoms less than 3 months, presence of complications which potentially required emergency surgery. Data on clinical features were obtained in 633 patients, of whom 452 were eligible to participate in the study. In 110 patients randomized to placebo the natural course of Crohn's disease was studied. Patients with ileocolonic involvement were younger than patients with either colonic or small intestinal involvement only. Classic ileitis terminalis was present in 14% of the patients. 49% of the patients had combined involvement of both the small and large intestine. 30% of patients had only small intestinal involvement, and in 21% colonic disease was present. Small intestinal involvement was associated with a significantly lower Crohn's Disease Activity Index (CDAI) than other anatomical locations of the disease. Perianal disease was more often associated with colonic than with small intestinal involvement. 60% of placebo patients with active disease at entry achieved at least a transient remission within the initial 5 months of study. After 2 years, 23% of patients with active disease at entry and 68% of patients with quiescent disease had reached or maintained a remission, respectively. By stepwise multiple linear regression analysis long duration of disease between diagnosis and randomization, normal serum albumin and combined involvement of small intestine and colon were identified as predictors of a more favorable outcome of patients treated with placebo. In contrast, extensive small bowel disease, treatment with steroids and bowel resection prior to study entry correlated with a less favorable outcome. However, by life table analysis outcome of previously untreated and treated patients in the placebo group was similar.

Interaction between transport of zinc and other solutes in human intestine.

To investigate the kinetics of zinc absorption, a jejunal segment from healthy human volunteers was intubated with a triple-lumen tube, and isotonic NaCl solutions containing 0, 0.1, 0.3, and 0.9 mM ZnCl2 were infused. There was secretion of zinc when zinc was not added to the test solution but absorption when zinc was added. Over the range of zinc concentrations infused, there were linear increases in the rate of zinc absorption. There was net absorption of sodium and water during the infusion of isotonic saline solution but no net absorption when zinc (0.9 mM) was added to this solution. This impairment was not prevented by adding glucose to the test solution, but the rate of zinc absorption was significantly enhanced in the presence of glucose. The rate of glucose absorption was not affected by adding zinc to a glucose-saline solution. Zinc absorption was significantly stimulated by the addition of glycylleucine to the test solution, whereas the corresponding mixture of glycine and leucine had no effect. The data allow the following conclusions: a) zinc absorption is selectively stimulated by organic solutes and b) zinc inhibits net absorption of sodium and water in the jejunum.