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Background and aims: Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are complex genetic disorders. CARD15/NOD2, a member of the Ced4 superfamily which includes Apaf-1 and CARD4/NOD1, has recently been associated with genetic predisposition to CD but additional genetic factors remain to be identified. Because CARD4/NOD1 shares many structural and functional similarities with CARD15, we tested its putative role in IBD. Patients and methods: The 11 exons of CARD4 were screened for the presence of variants in 63 unrelated IBD patients. The only non-private genetic variation encoding for a substitution in the peptidic chain was genotyped in 381 IBD families (235 CD, 58 UC, 81 mixed, and seven indeterminate colitis families) using a polymerase chain reaction-restriction fragment length polymorphism procedure. Genotyping data were analysed by the transmission disequilibrium test. Results: Five of nine sequence variations identified in the coding sequence of the gene encoded for non-conservative changes (E266K, D372N, R705Q, T787M, and T787K). Four were present in only one family. The remaining variant (E266K), which exhibited an allele frequency of 0.28, was not associated with CD, UC, or IBD. Furthermore, IBD patients carrying sequence variations in their CARD4 gene had a similar phenotype to those with a normal sequence. Conclusion: Our results suggest that CARD4 does not play a major role in genetic susceptibility to IBD. [ABSTRACT FROM AUTHOR]

No reliable identification of quiescent Crohn's disease (CD) patients with a high risk of relapse is available. The aim of this study was to develop a prognostic index to identify those patients. Untreated adult patients with quiescent disease (not induced by surgery) included in three phase III clinical trials were analysed retrospectively with respect to time to relapse. Nineteen factors related to biology, disease history, and topography were investigated. A relapse was defined as either a CD Activity Index (CDAI) > or = 200, a CDAI > or = 150 but over the baseline value by more than 100, or acute complications requiring surgery. The inclusion criteria were fulfilled by 178 patients. The median follow up was 23 months. The Cox model retained the following bad prognostic factors: age < or = 25 years, interval since first symptoms > 5 years, interval since previous relapse < or = 6 months, and colonic involvement (p < 0.001). Bootstrapping confirmed the variable selection. Patients were classified into three groups with an increasing risk of relapse (p < 0.001). The worst risk group was composed of patients presenting at least three of the four bad prognostic factors. These results make possible the design of clinical trials in quiescent CD patients with a high risk of relapse. [ABSTRACT FROM PUBLISHER]

The relationships between clinical activity, endoscopic severity, and biological parameters in Crohn's disease have not been thoroughly investigated and a link was therefore sought between these three elements. The following parameters were determined simultaneously in 121 consecutive patients with colonic or ileocolonic Crohn's disease: Crohn's disease activity index, Crohn's disease endoscopic index of severity, and serum albumin, alpha 2-globulin, alpha 1-antitrypsin, orosomucoid, C reactive protein, erythrocyte sedimentation rate, platelets, lymphocyte and polymorphonuclear cell counts, haematocrit, and faecal alpha 1-antitrypsin concentration. The distribution of these parameters was studied and transformation was used so that data matched the normal distribution closely. A weak but significant correlation (r = 0.32; p < 0.001) was found between clinical and endoscopic indices in the whole group of patients and this correlation seemed to be homogenous in various patient subgroups (clinically quiescent or active disease, pure colonic disease, untreated patients). Endoscopic or clinical indices were also found to be weakly linked with biological parameters (r < 0.50). Stepwise linear regression identified C reactive protein as predictive of the clinical index, and, successively, alpha 2-globulin, erythrocyte sedimentation rate, faecal alpha 1-antitrypsin, serum orosomucoid, and alpha 1-antitrypsin as predictive of the endoscopic index. Both predictions were poor--the biological variables accounting for only 22 and 44% respectively of the clinical and endoscopic index variations. In conclusion, Crohn's disease clinical activity seems to be virtually independent of the severity of the mucosal lesions and biological activity. [ABSTRACT FROM PUBLISHER]

The aim of this work was to study the jejunal secretion of immunoglobulins (Ig), albumin, and hyaluronan in response to jejunal perfusion of an elemental diet. A four lumen tube with a proximal occluding balloon at the angle of Treitz was used for jejunal perfusion in seven healthy volunteers (mean age 23 years). The length of the test segment was 40 cm. The jejunum was successively perfused with a control electrolyte solution for 80 minutes and with an elemental diet (containing 20.5 milligrams of free amino acids and 104.2 milligrams of oligosaccharides) for 100 minutes. The jejunal fluid concentrations of albumin, IgG, monomeric IgA (m-IgA), polymeric IgA (p-IgA), IgM, secretory component, and hyaluronan were measured and their jejunal outputs calculated. Within 20 minutes of starting perfusion with the elemental diet there was a significant increase in the secretion rates of albumin (x3.3), IgG (x5), M-IgA (x3.7), p-IgA (x2), IgM (x2), and secretory component (x1.6), but the hyaluronan secretion rate was not changed. The increase in m-IgA, p-IgA, IgM, and secretory component output suggests that intestinal perfusion of an elemental diet results in stimulation of secretory immunity. The increase in albumin and IgG output probably reflects a nutrient induced leakage from the plasma compartment. [ABSTRACT FROM PUBLISHER]

The aim of this study was to develop and validate an endoscopic index for assessing the severity of Crohn's disease. Endoscopic findings were prospectively collected by a multicentre group in 75 patients with Crohn's colitis according to a previously validated procedure. The presence of nine preselected lesions was recorded in the following segments (1) rectum, (2) sigmoid and left colon, (3) transverse colon, (4) right colon, and (5) ileum. In addition the extent of the diseased and ulcerated areas were estimated in each segment. These segmental data were recorded on a standard form, together with the endoscopist's global estimate of lesion severity. A stepwise multiple regression was used to derive an index which was correlated with the endoscopist's global evaluation of lesion severity. Four mucosal lesions: deep and superficial ulcerations, ulcerated and non-ulcerated stenosis, and both estimates of extent involved were selected and weighted to obtain a Crohn's Disease Endoscopic Index of Severity which correlated with the endoscopist's global appraisal of lesion severity (r = 0.83). This index was then prospectively shown to be valid in a further series of 113 colonoscopies (r = 0.81). The index was calculated in 54 patients with active Crohn's disease, before and at the end of a course of corticosteroids: index variations correctly reflected changes in colitis severity as evaluated by the endoscopists (r = 0.72). For endoscopists familiar with the data collection procedure, this Crohn's Disease Endoscopic Index of Severity should be of value in the follow up of patients, especially in clinical trials. [ABSTRACT FROM PUBLISHER]

The aim of this study was to measure the role of the duodenal loop in biliopancreatic secretion in man by infusing various stimuli at the ampulla of Vater and collecting duodenal contents at the ligament of Treitz, above an occluding balloon. Perfusion at 10 ml/min of a first mixture of aminoacids - phenylalanine (47.2 mmol), methionine (38.2 mmol), tryptophan (11 mmol), valine (61.6 mmol) - increased cholecystokinin (CCK) plasma concentrations and duodenal bile salt output (p less than 0.005) as compared with a control electrolyte solution, but did not change pancreatic enzyme secretion significantly; duodenal infusion of another aminoacid mixture - arginine (32.4 mmol), histidine (14.1 mmol), leucine (36 mmol), isoleucine (21.5 mmol), lysine (31 mmol), threonine (23 mmol) - did not change CCK plasma concentrations, bile salt or pancreatic enzyme output. The respective role of duodenal distension and endogenous CCK was investigated by perfusing the first aminoacid solution and the control solution at 2, 5, and 10 ml/min. Changing the perfusion rate of control solution from 2 to 5 ml/min led to a significant increase (p less than 0.01) in pancreatic secretion with no further increase at 10 ml/min. Bile salt output was not influenced by the perfusion rate of control solution. During the perfusion of the aminoacid solution, despite a stepwise increase in CCK release, the only significant change in pancreatic secretion was an increase of lipase output (p less than 0.05) when the infusion rate was raised from 2 to 5 ml/min. Our results suggest that duodenal CCK release (1) depends on the nature of aminoacids (2) has predominant role in the regulation of pancreatic secretion at low perfusion rate but is less effective when superimposed on a mechanical stimulus caused by duodenal distension (3) is a major stimulus for gall bladder contraction which is not influenced by duodenal distension. [ABSTRACT FROM PUBLISHER]

Symptomatic respiratory tract involvement with granulomatous bronchial lesions has not yet been described in Crohn's disease. We report two patients with colonic Crohn's disease and severe respiratory symptoms (dyspnoea associated in one of the patients with voicelessness); erythema, aphthoid and superficial ulcerations were found in the colon and whitish granulations in the bronchi at endoscopy. Non-caseating tuberculoid granulomas were found in the colonic mucosa of both patients, as well as in the bronchial mucosa of one of them; in the second a diffuse inflammatory infiltrate including epithelioid cells was found underneath an erosion of bronchial epithelium. Both patients improved on oral prednisone. These two patients probably had bronchial involvement by Crohn's disease. [ABSTRACT FROM PUBLISHER]

Chronic diarrhoea is frequent in acquired immune deficiency syndrome (AIDS) but has been poorly investigated so far. We report four patients with AIDS in whom diarrhoea and malabsorption were outstanding features, and who underwent extensive digestive investigations. Diarrhoea was a presenting symptom in all subjects and was of secretory type in three of them. D-xylose and vitamin B12 were malabsorbed in all cases; steatorrhea was found in the two patients who could ingest significant amounts of fat. Faecal alpha 1-antitrypsin clearance was increased in all subjects. Search for digestive pathogens showed unusual protozoans in all patients: in case 1, optical and electron microscopy revealed the presence in the cytoplasm of villous enterocytes of Microsporidia protozoans still unreported in AIDS. Stool and jejunal fluid examination showed Isospora belli in case 2 and Cryptosporidium in cases 3 and 4. On histological and ultrastructural study the former was localised in the cytoplasm of a few enterocytes and the latter was scattered throughout the villus and crypt brush border. Otherwise small intestinal histology only showed minor non-specific changes and the enterocytes were ultrastructurally normal. In patient 3 the slow marker intestinal perfusion technique showed a profuse fluid secretion in the duodenum and proximal jejunum. All patients needed prolonged total parenteral nutrition. Cryptosporidium and Microsporidia could not be eradicated despite multiple drug trials. Isospora belli was transiently cured by pyrimethamine-sulphadiazine. Only patient 2 is presently at home, and patients 1, 3, and 4 died after two, six, and nine months of total parenteral nutrition, respectively. [ABSTRACT FROM PUBLISHER]

To investigate the possible role of gut and pancreatic hormones in the adaptive responses to gut resection, plasma concentrations of the circulating hormones were measured, in response to a test breakfast, in patients with either small or large intestinal resection and in healthy control subjects. In 18 patients with partial ileal resection a significant threefold rise was found in basal and postprandial levels of pancreatic polypeptide, a fourfold increase in motilin, and more than a twofold increase in gastrin and enteroglucagon levels compared with healthy controls. In contrast, nine patients with colonic resection had a threefold rise in levels of pancreatic polypeptide only. One or more of these peptides may have a role in stimulating the adaptive changes found after gut resection. [ABSTRACT FROM PUBLISHER]

In 11 conscious volunteers, the jejunal absorption was measured during basal state and during the simultaneous intravenous infusion of small doses of gastrin, secretin, cholecystokinin, glucagon and gastric inhibitory polypeptide. The blood levels of gastrin, secretin, glucagon, and GIP were measured by RIA and were close to those achieved after a meal. The basal net absorption of water and electrolytes was reversed to a net secretion during the hormonal infusion. These results suggest that the jejunal secretion observed after a meal in man may be mediated by hormones released by the meal. [ABSTRACT FROM PUBLISHER]

Four patients with chronic non-specific ulcerative duodenojejunoileitis (CNSUDJI) are reported. The clinical picture included abdominal pain, fever, and a malabsorption syndrome. Main rediological findings were diffuse narrowing of the jejunal loops with total effacement of the mucosal folds. Multiple peroral biopsies of the small intestine showed various degrees of mucosal abnormalities from total villous atrophy to normal villi, but ulcerations were diagnosed only by operative full thickness biopsies or resection of the small bowel. The ulcerative process was associated with well-documented coeliac disease in two patients: in one of them it occurred as a fatal complication involving also the colon, three years after the start of a gluten free diet, while the disease was in full clinical and histological remission. In the other case, coeliac disease was revealed by obstructive symptoms due to stenosing ulcerations; five months after surgical resection of the stenosis, institution of a gluten free diet induced a dramatic improvement. In the two other patients ulcerations were not associated with coeliac disease: one of them had a patchy villous atrophy and resisted a gluten free diet and total parenteral nutrition; she was improved by and dependent upon steroids but finally died. The last patient had normal villous height; ulcerations were located exclusively along the mesenteric border of the small bowel; he had a low-grade protracted evolution resisting any form of therapy and developed a peripheral neuropathy of unknown aetiology. On the basis of our cases and of a review of the literature the discussion focuses on the difficulty in diagnosing CNSUDJI, its relationship with coeliac disease, and its management and prognosis. [ABSTRACT FROM PUBLISHER]

A perfusion technique with a proximal occluding balloon has been used to study the absorption of glucose, sodium, and water from the human jejunum at different rates of flow. The absorption of glucose and water was significantly higher with the balloon deflated than inflated, probably because of reflux of infused solution above the point of infusion. Above the inflated balloon 0 to 4·2 ml/min of endogenous secretions could be recovered. Increasing flow rates increase the glucose absorption rate; a single relationship could be found between the glucose load and glucose absorption rate, and single values for the maximum velocity and for the half saturating load were calculated whatever the infusing rate and the initial glucose concentration. The stimulating effect of glucose on water and sodium movement increases gradually when the initial sugar concentration varies from 14 to 133 mM/1. Above this concentration a drop in water and sodium movement is observed, although the initial sodium concentration is kept constant. High flow rates result in a decrease of water absorption and an increase in sodium and potassium secretion rates. [ABSTRACT FROM PUBLISHER]