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.

No abstract

Assessment of intestinal absorptive function requires techniques for correcting transport constants for diffusion barrier resistance. These studies were done to develop such techniques for use in vivo. In one method the functional thickness of the unstirred water layer (d) in rat jejunum was quantitated electrically, and its minimal surface area (Sw) was measured directly. From these values the diffusion barrier resistance (d/Sw) decreased from 0.041 to 0.022 as the perfusion rate of the intestine was increased from 1.5 to 15 ml/min. In the second method apparent passive permeability coefficients (*P) were measured for a series of saturated fatty acids, and these increased with chain length. However, at the longest chain lengths tested, *P became proportional to their free diffusion coefficients, indicating that uptake was limited by the rate of diffusion up to the microvillus surface. From the rates of uptake of such diffusion-limited probes, the diffusion barrier resistance was again calculated and found to decrease from 0.041 to 0.022 as the rate of perfusion was increased from 1.5 to 15 ml/min. Over this same range of perfusion rates, the apparent Michaelis constant (*Km) for D-glucose transport decreased from 18.2 to 10.0 mM. Using either set of resistance terms and these apparent Km values, the true Km value for glucose transport in vivo was found to equal 0.8 mM when the barrier resistance was extrapolated to zero. Thus these data indicate that diffusion-limited probes can be utilized to measure unstirred layer resistance in the intestine of a live animal so that absolute transport parameters can be determined in vivo in experimental animals and, presumably, in humans.

To assess the effects of magnesium chloride or magnesium sulfate on the release of cholecystokinin from the duodenum, outputs of trypsin and bilirubin were quantified during perfusion of the duodenum with isotonic solutions of these salts. Net intestinal water transport was also quantified. The results suggest that magnesium ion in the duodenum is a relatively weak stimulus to the pancreas and gallbladder, an action not augmented by the concomitant presence of the sulfate ion. As determined by this human bioassay method, magnesium is a weak stimulant to cholecystokinin release. Furthermore, magnesium chloride inhibits net jejunal water absorption and magnesium sulfate is even more potent, promoting net water secretion, effects which cannot be entirely attributed to cholecystokinin release.