Background: Budesonide is a corticosteroid with high topical anti‐inflammatory activity and low systemic activity due to rapid inactivation. We have assessed the efficacy and safety of an oral controlled ileal release (CIR) preparation of budesonide for maintenance of remission in patients with ileal or ileocaecal Crohn’s disease. Methods: In a double‐blind, multicentre trial, 75 patients in clinical remission (Crohn’s Disease Activity Index, CDAI, ≤ 150) were randomly assigned to receive placebo, budesonide 3 mg or budesonide 6 mg daily for 12 months. Trial drugs were given at a fixed dose and without concomitant medication. The primary outcome measure was relapse, defined as a CDAI > 150 together with an increase of at least 60 units from entry. A patient was also considered to have a relapse if withdrawn from the study due to clinical deterioration, whether or not a CDAI value could be calculated at that time. Results: There were no statistically significant differences in the relapse rate at any time‐point throughout the study. By 12 months the proportion of patients having relapsed were 48, 46 and 60% in those patients treated with budesonide 6 mg, 3 mg and placebo, respectively (N.S.). Treatments were well tolerated, and the proportion of patients with suppressed adrenal function (according to predetermined criteria) were 50% (6 mg), 26% (3 mg) and 17% (placebo) (P = 0.096). Conclusions: In the present study, relapse rate and time to relapse were similar in the patients treated with budesonide CIR, 6 mg daily or 3 mg daily or with placebo, throughout 12 months. This is in contrast to the two previous trials with identical design, where a significant effect of budesonide CIR in prolonging the median time to relapse was found. Possible reasons for the negative results of the present study include small sample size, and the fact that there was a high placebo response.

Summary Background : A high prevalence of osteoporosis has been noted in Crohn's disease, but data about fractures are scarce. Methods : The relationship between low bone mineral density and the prevalence of vertebral fractures was studied in 271 patients with ileo‐caecal Crohn's disease in a large European/Israeli study. One hundred and eighty‐one currently steroid‐free patients with active Crohn's disease (98 completely steroid‐naive) and 90 steroid‐dependent patients with inactive or quiescent Crohn's disease were investigated by dual X‐ray absorptiometry scan of the lumbar spine, a standardized posterior/anterior and lateral X‐ray of the thoracic and lumbar spine, and an assessment of potential risk factors for osteoporosis. Results : Thirty‐nine asymptomatic fractures were seen in 25 of 179 steroid‐free patients (14.0%; 27 wedge, 12 concavity), and 17 fractures were seen in 13 of 89 steroid‐dependent patients (14.6%; 14 wedge, three concavity). The prevalence of fractures in steroid‐naive patients was 12.4%. The average bone mineral density, expressed as the T‐score, of patients with fractures was not significantly different from that of those without fractures (−0.759 vs. −0.837; P=0.73); 55% of patients with fractures had a normal T‐score. The bone mineral density was negatively correlated with lifetime steroids, but not with previous bowel resection or current disease activity. The fracture rate was not correlated with the bone mineral density (P=0.73) or lifetime steroid dose (P=0.83); in women, but not in men, the fracture rate was correlated with age (P=0.009). Conclusions : The lack of correlation between the prevalence of fractures on the one hand and the bone mineral density and lifetime steroid dose on the other necessitates new hypotheses for the pathogenesis of the former.

No abstract

A gastric mucosa in vitro model for studies of experimental Helicobacter pylori infections has been developed. Biopsy specimens were taken from pig gastric mucosa, infected with H. pylori, and cultured for up to 72 h. To determine the degree of H. pylori adhesion, specimens were vigorously rinsed by vortexing five times before measuring viable count and urease activity. The results showed that it is possible to culture pig gastric mucosa in vitro with maintained viability for at least 72 h. According to the viable count, the bacteria survived and multiplied during the whole culture period. The percentage viable H. pylori in the specimens after rinsing and the urease activity increased with time of culture. The results indicate that the bacteria in the gastric specimens were viable after 72 h and that there was a time-dependent increase in bacterial adhesion to the specimens. This in vitro gastric mucosa model promises to be an applicable and reproducible method, with high capacity, for both pathogenic and mechanistic studies of H. pylori infection.

SUMMARY The early histological features of indomethacin‐induced jejunal injury in the rat are described in tissues preserved by perfusion‐fixation with 10% formolsaline. After an oral dose of indomethacin (15 mg/kg, known to cause severe multifocal ulceration of the rat jejunum), groups of rats were anaesthetized with subsequent perfusion‐fixation of the gastrointestinal tract at 1, 2, 3, 6 and 48 h after dosing. Using routine light microscopic techniques, we have observed a sequence of four distinct stages, in time, of small intestinal injury. The earliest histological features were shortening of the villi, epithelial stratification, basal lamina degeneration, eosinophil degranulation and infiltration of the epithelium prior to infiltration of the mucosa by neutrophils. We consider that these earliest changes, seen at 1, 2 and 3 h, represent a distinct histological entity termed Type 1 change or villous ‘tufting’. Type 2 change includes all of the features of Type 1 change plus the subsequent infiltration of the mucosa by neutrophils at 2, 3 and 6 h. Type 3 change includes necrosis of the upper‐third of the villi and was mainly seen at 3 and 6 h. Type 4 change describes extreme injury to more than one‐third of the mucosa with severe, acute inflammation and perforation of the bowel wall by 48 h. Although a small number of neutrophils had appeared to infiltrate the mucosa as early as 2 h after dosing, they were only significantly increased at 3, 6 and 48 h. Possible pathogenic mechanisms involved in shortening of villi as a result of smooth muscle contraction and the role of mucosal eosinophils in NSAID‐induced jejunal injury in the rat are discussed.