Omega-3 fatty acids and low carbohydrate diet for maintenance of remission in Crohn's disease. A randomized controlled multicenter trial. Study Group Members (German Crohn's Disease Study Group).

BACKGROUND: There is no established therapy for maintaining remission in patients with Crohn's disease. Following different suggestions from the literature, two potential interventions for maintaining remission were tested against placebo, using either 5 g/day of a highly concentrated omega-3 fatty acid compound or a carbohydrate-reduced diet (84 g/day). METHODS: A total of 204 patients were recruited after they had had an acute relapse. After remission (CDAI < or = 150) was attained with steroid therapy, patients were randomized to receive either omega-3 fatty acids (n = 70), placebo (n = 65), or diet (n = 69). Low-dose prednisolone was given to all patients for the first 8 weeks of intervention. CDAI and an acute-phase protein (CRP) were used as criteria for a relapse. RESULTS: The proportion of patients without relapse within a year were similar in the placebo and active treatment group (intention-to-treat analysis: placebo, 30%; active treatment, 30%; protocol-adhering patients, 29% versus 28%). Patients did gain benefit (53%; p = 0.023) for as long as they maintained the diet. However, intention-to-treat analysis (diet group, 40%) did not show a noticeable difference when compared with placebo. CONCLUSIONS: Omega-3 fatty acids did not show an effect on extending the remission in Crohn's disease. For the diet patients the question remains whether the noncompliant patients dropped out early because they sensed a relapse approaching or whether their condition deteriorated because they failed to comply with the diet.

Budesonide prolongs time to relapse in ileal and ileocaecal Crohn's disease. A placebo controlled one year study.

BACKGROUND AND AIMS: To evaluate the efficacy and safety of the topical corticosteroid budesonide, given in an oral controlled release formulation for maintenance of remission in patients with ileal and ileocaecal Crohn's disease (CD). PATIENTS AND METHODS: Out of 176 patients with active CD who had achieved remission (CD activity index score < or = 150) after 10 weeks' treatment with either budesonide or prednisolone, 90 were randomised to continue with once daily treatment of 6 mg budesonide, or 3 mg budesonide or placebo for up to 12 months in a double blind, multicentre trial. Time to symptomatic relapse was calculated using Kaplan-Meier estimates. Morning plasma cortisol was measured at clinic visits and a corticotropin stimulation test was performed after three months of treatment. RESULTS: Thirty two patients were allocated to the 6 mg budesonide group, 31 to the 3 mg group, and 27 to the placebo group. After three months, 19 per cent of the patients in the 6 mg group had relapsed, compared with 45 per cent in the 3 mg group and 44 per cent in the placebo group (p = 0.047). The corresponding results after 12 months was 59 per cent in the 6 mg budesonide group, 74 per cent in the 3 mg group, and 63 per cent in the placebo group (p = 0.44). The median time to relapse or discontinuation was 258 days in the 6 mg group, 139 days in the 3 mg group, and 92 days in the placebo group (p = 0.021). Mean morning plasma cortisol values increased from entry in all three groups with no statistically significant differences at 12 months. All 13 patients remaining in the placebo group after three months had a normal corticotropin stimulation response, compared with 18 of 23 patients in the 6 mg, and 19 of 21 in the 3 mg budesonide groups (p = 0.14). Acne and moon face were slightly more common in the budesonide groups. CONCLUSION: 6 mg budesonide once daily is significantly more efficacious than placebo in prolonging time to relapse in CD, and causes only minor systemic side effects.

A comparison of budesonide with prednisolone for active Crohn's disease.

BACKGROUND: Patients with active Crohn's disease are often treated with corticosteroids, but the treatment has many side effects. Budesonide is a potent, well-absorbed corticosteroid, but because of a high rate of first-pass metabolism in the liver, its systemic bioavailability is low. METHODS: We conducted a randomized, double-blind, 10-week trial comparing the efficacy and safety of an oral controlled-release form of budesonide with the efficacy and safety of prednisolone in 176 patients with active ileal or ileocecal Crohn's disease (88 patients in each treatment group). The dose of budesonide was 9 mg per day for eight weeks and then 6 mg per day for two weeks. The dose of prednisolone was 40 mg per day for two weeks, after which it was gradually reduced to 5 mg per day during the last week. RESULTS: At 10 weeks, 53 percent of the patients treated with budesonide were in remission (defined as a score < or = 150 on the Crohn's disease activity index), as compared with 66 percent of those treated with prednisolone (P = 0.12). The mean score on the Crohn's disease activity index decreased from 275 to 175 in the budesonide group and from 279 to 136 in the prednisolone group (P = 0.001). Corticosteroid-associated side effects were significantly less common in the budesonide group (29 vs. 48 patients, P = 0.003). Two patients in the prednisolone group had serious complications (one had intestinal perforation and one an abdominal-wall fistula). The mean morning plasma cortisol concentration was significantly lower in the prednisolone group than in the budesonide group after 4 weeks (P < 0.001) and 8 weeks (P = 0.02) of therapy, but not after 10 weeks. CONCLUSIONS: Among patients with active Crohn's disease, both controlled-release budesonide and prednisolone are effective in inducing remission. In this trial, prednisolone reduced scores on the Crohn's disease activity index more, whereas with budesonide there were fewer glucocorticoid-associated side effects and less suppression of pituitary-adrenal function.

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.

[Endemic sprue]. / Die einheimische Sprue.

Coeliac disease or Gluten enteropathy is a well-defined, but in its pathogenesis poorly understood syndrome. Diarrhoea, steatoroea and malnutrition due to damage and transformation of the small intestinal mucosa are induced by cereal proteins (gliadin) in genetically predisposed children and adults. Local interactions between immunocompetent cells and structural elements of the small intestinal mucosa have been investigated by immunochemical, ultrastructural and cell biological methods. In this review we discuss the events produced by defined gliadin derivates in vivo and in vitro. They suggest a complex mucosal reaction pattern, involving inflammatory and hyperergic manifestations. The cytotoxicity of gliadin is discussed in the context of defined mediators of lymphocyte and inflammatory cell interactions. The importance of structural elements of the lamina propria and the epithelium as target tissues of the immunological attack and its impact on the local environment is elucidated. Gliadin hypersensitivity is regarded as a genetically determined disposition which can be correlated to the HLA system. The distribution of HLA class I and II antigens with respect to T- and B-lymphocyte functions is described. The diagnosis of coeliac disease and the scientific exploration of cell culture techniques have been greatly improved by modern endoscopy. However, the specificity and sensitivity of laboratory tests for coeliac disease are still controversial The value of determining autoantibodies and antigliadin antibodies is evaluated. Clinical syndromes associated with coeliac disease typically involve immunological phenomena and a comprehensive review of the relevant experiences will be presented. Finally, the general prognosis of coeliac disease and the risk of developing malignancies with respect to the necessity and feasibility of a stringent, lifelong gluten-free diet and patient compliance are discussed.

[The correlation of psychosocial stress and disease activity in patients with Crohn disease and ulcerative colitis]. / Uber den Zusammenhang von psychosozialem Stress und Krankheitsaktivität bei Patienten mit Morbus Crohn und Colitis ulcerosa.

The following study examines the correlation of psychosocial stress and disease activity in patients suffering from chronic inflammatory bowel diseases. 70 patients with Crohn's disease and 44 patients with ulcerative colitis took part in this study. Using an inventory for the registration of life-changing events, psychosocial life-events of the last 24 months were inquired. The disease activity was registered by an activity index created for this particular purpose. Due to the formulation of the question, pure subjective data were not considered. With regard to the social data, the two samples can very well be compared with other epidemiological studies. For the group of Crohn-patients, a significant correlation between psychosocial stress and a subsequent increased disease activity was demonstrated. Surprisingly, the group of patients with ulcerative colitis did not show this correlation.

Effect of pancreatic atrophy and hypertrophy on the small intestine.

Intestinal enzyme activities were investigated in mice with spontaneously occurring exocrine pancreatic insufficiency (EPI), in rats after induction of pancreatic insufficiency by intraductal injection of oleic acid, and in rats after feeding a proteinase inhibitor (Camostate) which induced a marked pancreatic hypertrophy. An increase in saccharase activity and in vitro uptake of L-phenylalanine was found in EPI mice, while activities of alkaline phosphatase and lactase were not altered. In oleic acid induced pancreatic insufficiency and in pancreatic hypertrophy no alterations in enzyme activities were observed. Morphometric analysis revealed no alterations in mucosal surface of EPI mice. It was suggested that the small intestine adapts fuctionally to severe and long lasting pancreatic insufficiency, but not to pancreatic hypertrophy.

[Differential diagnostic evaluation of chronic pancreatitis in relation to pancreatic cancer based on clinical, laboratory chemical and diagnostic parameters. Studies of 174 patients in 10 years]. / Die differentialdiagnostische Abgrenzung der chronischen Pankreatitis zum Pankreaskarzinom an Hand klinischer, laborchemischer und diagnostischer Parameter. Beobachtungen an 174 Patienten über einen Zeitraum von 10 Jahren.

174 patients with chronic pancreatic diseases, 30 patients with pancreatic carcinoma and 144 with chronic relapsing pancreatitis, 50 of them with calcifications, were observed in the Department of Internal Medicine of the University of Marburg/FRG between 1972 and 1982. In order to differentiate between carcinoma and relapsing pancreatitis the data of these patients were analysed retrospectively with regard to patient history, actual complaints, findings of laboratory, sonography, ERCP and X-ray investigations. The following results were obtained: Of discriminating value are steatorrhoe, local palpatory pain, alcohol ingestion, a history of earlier attacks and relapsing pain situations; however, general abdominal pain, nausea, vomiting and weight loss (if not exactly specified) are not. Within the laboratory findings bilirubin, GOT, alkaline phosphatase, gamma-GT, serum potassium, blood sugar and chymotrypsin content of the stool were significant while serum and urine amylase were similarly distributed within the groups of patients. Carcinoma and chronic relapsing pancreatitis can be identified by sonography in the majority of patients, but calcifications of the pancreas were rarely demonstrated during this observation period. The obstruction of the extrahepatic bile ducts--mostly due to a carcinoma of the pancreas head--was usually well documented by sonography. Intraabdominal air proofed to be the most disturbing factor. In carcinoma patients, the ERCP is important in demonstrating a complete obstruction of the pancreatic duct and stenosis and dilatation of the extrahepatic bile ducts. In patients with chronic relapsing pancreatitis the pancreatic duct alterations such as dilatations and partial stenosis are well documented by ERCP especially if calcifications occur. In patients without calcifications, dilatation of the branches of the main duct are less relevant in the diagnosis of pancreatic diseases. Radiological demonstration of calcification of the pancreatic area is important for the differential diagnosis. Longstanding characteristical complaints, symptoms and calcifications within the pancreatic area are the most relevant factors in discriminating carcinoma and chronic relapsing pancreatitis.

[Effect of osmolality on the gastrointestinal permeation of various carbohydrates in healthy persons]. / Einfluss der Osmolalität auf die gastrointestinale Permeation verschiedener Kohlenhydrate am Gesunden.

The effect of a high osmotic solution on active and passive sugar permeation was investigated in 19 healthy volunteers. The reduced rate of active sugar absorption (3-O-MG and xylose) out of a high osmotic solution was interpreted as a consequence of an impaired emptying of the stomach. The increased passive permeation of intact disaccharides applied in hyperosmolar solution demonstrates an increased gastrointestinal permeability. Intubation studies suppose increased disaccharide absorption out of hyperosmolar solution in the stomach, i.e. high osmolar solutions increase gastric mucosal permeability.

Cytotoxicity of lectins on rat intestinal mucosa enhanced by neuraminidase.

The lectins wheat germ agglutinin (WGA) and Concanavalin A (ConA) were perfused into an isolated small intestinal segment alone or after prior perfusion with neuraminidase for a 10 day period in the rat. Intestinal morphometry, intraepithelial Lymphocyte (IEL) and round cell content as well as digestive capacity was measured in the loop and in the adjacent segments. Both lectins induce a mucosal transformation in all segments but ConA is more effective than WGA. Pre-incubation with neuraminidase enhances the action of ConA throughout, whereas only a partial enhancement of the effect of WGA is observed. The mucosal transformation after long term perfusion with the lectins resembles the hyperregenerative adaptation of the mucosa due to gluten in coeliac disease and may thus serve as an animal model for this disease.

Comparative radiological and morphological study of human pancreas. Pancreatitis like changes in postmortem ductograms and their morphological pattern. Possible implication for ERCP.

A postmortem study by ductography and histology was performed on 69 human pancreata with no clinical or histological signs of chronic pancreatitis. The ductograms, supplemented by five postmortem ductograms of chronic pancreatitis, were independently evaluated by six clinicians, skilled in ERCP; the degree of alteration was estimated by simple rating, forced choice rating, and by determination of the grade of chronic pancreatitis, Histologically, the amount of intraductal epithelial proliferation, periductal, intralobular and perilobular fibrosis, intraductal protein plugs, and fat necrosis was determined by semiquantitative methods. The six ductographical evaluations significantly differed in the level of their data, but corresponded in the range of distribution. All evaluations were correct regarding judgement of ductograms from patients with chronic pancreatitis. Ductograms of patients without chronic pancreatitis, however, were also frequently classified as chronic pancreatitis; overall 81% (minimal 37%, moderate 33%, severe 11%). This high level of false positive diagnosis indicates the frequency of pancreatitis like lesions in the main duct and its side branches in patients without chronic pancreatitis. Ductal lesions were significantly correlated with perilobular fibrosis. This finding favours the assumption, that in the non-inflamed pancreas, perilobular fibrosis plays a key-role in the development of ductal alterations, as in chronic pancreatitis. Perilobular fibrosis may result from intralobular inflammation caused by age-dependent intraductal epithelial hyperplasia.

European Cooperative Crohn's Disease Study (ECCDS): colonoscopy.

130 patients with Crohn's disease were colonoscopied in a multicenter trial. The obtained data were analyzed with respect to gathering information on the inflammation pattern, as well as on the importance and prognostic value of special lesions in Crohn's colitis. In 52 patients a second endoscopy was performed at the end of the 2-year study period. Ulcerations and aphthous lesions were the most common lesions, followed by pseudopolyps, cobblestone lesions and stenosis. In general, there was an increasing, distal gradient in the frequency of severe lesions. patients with Crohn's colitis alone had more signs of inflammation than patients with additional involvement of the small intestine. A segmental pattern was the most common form of inflammation. The group of patients (14%) with a continuous pattern did not deviate from the whole collective in clinical activity. In patients with previous resections, inflammation near the anastomosis was accompanied more often than not by stenosis. Patients with ulcerations had a rather short time since confirmation of the diagnosis. Cobblestone lesions and pseudopolyps correlated with short symptomatology. During the follow-up of the study, patients taking steroids or a combination with prednisolone and sulfasalazine seem to have better results than those under placebo or sulfasalazine alone, as regards the more severe symptoms.

Effect of antrectomy on small intestinal structure and function in the rat.

Antrectomy reduced the levels of circulating gastrin but did not change jejunal morphology. In vitro and in vivo absorption as well as the activity of some brush border enzymes were increased. The observed alterations are discussed on the basis of antrectomy-induced alterations in the release of gastrointestinal hormones, gastric and pancreatic secretion and gastric emptying.

Quantitative histomorphometric study of the jejunal mucosa in chronic alcoholics.

Jejunal suction biopsies of 18 chronic alcoholics (alcohol intake of more than 100 g of ethanol per day for several years) and 10 nonalcoholic control subjects were analyzed quantitatively using the microdissection technique described by Clarke. Both groups were comparable concerning age, body weight and sex. The duration of alcohol withdrawal in the alcoholics before the biopsy was taken ranged from 2 to 7 days. The mean number of villi and surface per villus was slightly lower in the jejunum of the alcoholics. The mucosal surface per mm2 was significantly lower in the latter group when compared to the controls (p less than 0.005). The ratio of the number of crypts per villi was increased in the alcoholics (p less than 0.05). Histological evaluation revealed a more than twofold increase in the number of interepithelial mononuclear cells (p less than 0.005), while the number of epithelial cells/100 microns of villous mucosa and the mean height of the epithelial cells were comparable in both groups.