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Biomedical subjects

J F Colombel

Publications and source records attributed to J F Colombel.

At least 181 records · Page 10Linked to original sources

[What is the prognosis in unclassified colitis? Results of a cohort study of 104 patients in the Northern-Pas-de-Calais region].

Acute unclassified colitis could be the first attack of inflammatory bowel disease, particularly chronic ulcerative colitis or acute non specific colitis regarded as being of infectious origin without recurrence. The aim of this work was to determine the outcome of 104 incidental cases of acute unclassified colitis diagnosed during the year 1988 at a census point made 2.5 to 3 years later and to search for demographic and clinical discriminating data for final diagnosis. Thirteen patients (12.5%) were lost to follow up. Another final diagnosis was made in three other patients: two had salmonellosis and one diverticulosis. Of the remaining 88 patients, 46 (52.3%) relapsed and were subsequently classified as inflammatory bowel disease: 54% ulcerative colitis, 33% Crohn's disease and 13% chronic unclassified colitis. Forty-two (47.7%) did not relapse and were considered to have acute non specific colitis. The mean age at onset was significantly lower in patients with inflammatory bowel disease (32.3 years) than in patients with acute non specific colitis (42.6 years) (P < 0.001). No clinical data (diarrhea, abdominal pain, bloody stool, mucus discharge fever, weight loss) was predictive of the final diagnosis. In this series, 52.3% of patients initially classified as having an acute unclassified colitis had a final diagnosis of inflammatory bowel disease after a 2.5-3 years follow-up. These data warrant a thorough follow up of acute unclassified colitis, especially when it occurs in patients < 40 years.

Acute Disease↗

[Maintenance treatment of Crohn's disease using orally administered mesalazine (Pentasa). A controlled multicenter study. The Study Groups on the Treatment of Inflammatory Digestive Disorders].

BACKGROUND: Mesalamine provides a new therapeutic approach in treating Crohn's disease. METHODS: To assess the efficacy and safety of slow-release mesalamine (Pentasa) in maintaining remission in Crohn's disease, 161 patients with inactive disease were randomized to receive either Pentasa (2 g/day) or placebo in a 2-year double-blind, multicenter trial. Two strata were defined according to the duration of their remission: < 3 months (n = 64) or 3-24 months (n = 97), presumed to be high and low relapse risk strata, respectively. RESULTS: The probability of relapse was higher in the short-remission placebo group than in the three other groups (p < 0.003), showing there was a significant benefit from Pentasa in the high relapse risk stratum. In this stratum, the 2-year on-going remission rate was of 29% +/- 9% and 45% +/- 11% (mean +/- SD) in the placebo and Pentasa groups, respectively. The incidences of side effects were similar in both groups. CONCLUSION: Pentasa (2 g/day for 2 years) is a safe and effective maintenance treatment for Crohn's disease when given within 3 months of achieving remission.

Administration, Oral↗

[Decrease of fecal beta-galactosidase activity in Crohn disease].

An increased degradation of colonic mucus by bacterial enzymes might participate in the development of mucosal lesions in inflammatory bowel disease. The biodisponibility of drugs used in the treatment of such disease relies upon the metabolic activity of colonic bacterial flora. This activity can be indirectly assessed by measuring fecal enzymatic activities. The aim of this study was to compare fecal beta-galactosidase (beta-gal) activity in controls, in patients suffering from extradigestive inflammatory disease and in patients with Crohn's disease (CD). Three groups were studied including 11 healthy volunteers (6 F, 5 M) mean age 29 years (21-37), 20 patients with rheumatoid arthritis (RA) (17 F, 3 M), mean age 61.5 years, and 34 patients with non operated CD (21 F, 13 M) mean age: 27 years (13-50). The Crohn disease activity index (CDAI) was > 150 in 24 and < 150 in 10. beta-gal activity was measured in fecal extracts by its ability to hydrolyze paranitrophenyl beta-D-galactopyranoside and expressed as units of enzymatic activity/gram of fecal proteins. beta-gal activity was significantly decreased in patients with CD (16 +/- 4.5 U/g) (m +/- sem) as compared with patients with RA (353 +/- 64 U/g) (P < 0.0001) and to controls (263 +/- 40 U/g) (P = 0.002). beta-gal activity was not significantly different in controls and in patients with RA. Patients with active CD had a significantly lower beta-gal activity than patients with quiescent CD (9.5 +/- 3.7 U/g vs 31.4 +/- 11.5 U/g) (P = 0.006).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Chronic gastritis: prevalence in the French population. CIRIG.

Chronic gastritis (CG) which can be associated with severe complications, is a frequent phenomenon in gastroenterological practice. No data concerning the prevalence of GC are available in France. The aim of this study was to evaluate the prevalence of CG on biopsy specimens in the French population. All outpatients coming from different towns of seven French areas and undergoing an upper endoscopy on one or two randomly selected consecutive days were included in the study. A case report form was filled out and 5 biopsy specimens were taken from the fundus and antrum. Pathologists graded the specimens on the basis of Whitehead's classification. Seven hundred and forty-two patients were enrolled by 102 private gastroenterologists. Mean age was 53 years; 52% were males. Endoscopically, the gastric mucosa was abnormal in 53%. Superficial and atrophic CG was diagnosed in 53% of cases. Superficial gastritis was observed in 101 patients (14%), antral chronic atrophic gastritis (CAG) in 189 (26%) and fundic CAG in 17 (2%). Patients with CAG were significantly older than the other patients. There were more smokers and heavy alcohol drinkers in the group of CAG patients. Endoscopy and histology were in accordance in only 55.2% of the patients: most cases of CAG were not detected by endoscopy. These results are similar to other studies in European populations. The principal pattern among the various types of gastritis was CAG. The other forms were rare. Autoimmune gastritis was uncommon in this French population (4% of the CAG patients).

Adolescent↗

Interleukin 5 messenger RNA expression by eosinophils in the intestinal mucosa of patients with coeliac disease.

Interleukin 5 (IL-5), the major factor involved in eosinophil differentiation, is produced by T cells or mast cells. In the present study, we found that eosinophils infiltrating the mucosa of four patients with active coeliac disease also express the IL-5 mRNA. No positive signal was obtained in normal duodenum tissues and in the cell infiltrate from patients submitted to gluten restriction. The identification of labeled mucosal cells as eosinophils relied on their typical morphology. Moreover, highly purified blood eosinophils from three out of four patients with eosinophilia were also strongly labeled with the IL-5 antisense but not with the corresponding sense probe. Together, these results suggest that eosinophils have the capacity to synthesize IL-5, which could contribute to paracrine interactions with T and B cells and, in autocrine fashion, locally participate, through binding to the IL-5 receptor, to eosinophil differentiation and activation. These data might have implications not only in the pathology of coeliac disease but also in other diseases associated with eosinophil infiltration.

Celiac Disease↗

PAF-acether and acetylhydrolase in stool of patients with Crohn's disease.

PAF-acether (PAF) is a phospholipid mediator with potent biological effects on the digestive tract. We report the presence of PAF in stool of patients with active Crohn's disease (39.1 +/- 13.5 ng/g of stool, mean +/- SEM, N = 19) and its absence in patients with irritable bowel syndrome with diarrhea and diarrhea with malabsorption. Fecal PAF acetylhydrolase activity was higher (P less than 0.04) in patients with Crohn's disease as compared to patients with irritable bowel syndrome with diarrhea and diarrhea with malabsorption. We also report a solid-phase extraction of fecal PAF using silica minicolumns, which yielded results highly correlated with those obtained with a high-performance liquid chromatography method (r = 0.86, P less than 0.001, N = 16). These findings may allow us to implicate PAF in the onset and perpetuation of digestive tract inflammatory symptoms observed during Crohn's disease. They would warrant to investigate the influence of various therapeutic agents, including PAF antagonists, on fecal PAF levels during inflammatory digestive ailments.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

Acute exposure of small intestine to ethanol induces mucosal leakage and prostaglandin E2 synthesis.

The small intestines of healthy volunteers were challenged with ethanol during regional perfusion of a defined jejunal segment. Infusion of 30 mL of 5000 mmol/L ethanol to the perfused jejunal segment gave a maximum ethanol concentration of 973 +/- 98 (SEM) mmol/L in the jejunum lumen. This ethanol challenge induced within 20-30 minutes a 10-fold increase in albumin (P less than 0.001) and a two-fold increase in the glycosaminoglycan hyaluronic acid (P less than 0.05) in the perfusion fluid. Later during the challenge and simultaneously with a decreased jejunal loss of albumin, the jejunal recovery of prostaglandin E2 increased fourfold (P less than 0.01). The jejunal fluid concentrations of histamine and eosinophil cationic protein remained stable during the ethanol challenge. No changes in the jejunal appearance of albumin or other measured substances were seen when the maximum jejunal fluid concentrations of ethanol were less than 400 mmol/L achieved during challenge with smaller amounts of ethanol. The increased jejunal fluid appearance of hyaluronic acid after ethanol challenge indicates increased leakage from the interstitial/lymph fluid of the gut wall due to altered mucosal permeability. The relatively larger jejunal losses of albumin suggest that ethanol induces increased microvascular permeability of the jejunum as well.

Adult↗

Decreased faecal exoglycosidase activities identify a subset of patients with active Crohn's disease.

1. alpha 1-Proteinase inhibitor (alpha 1-antitrypsin) is excreted in a deglycosylated form (M(r) 38,000) in the faeces of healthy subjects and in patients with quiescent Crohn's disease. By contrast, in most patients with active Crohn's disease, alpha 1-proteinase inhibitor is excreted in a glycosylated form (M(r) 51,000). 2. Faecal extracts containing deglycosylated alpha 1-proteinase inhibitor are able to deglycosylate alpha 1-proteinase inhibitor by an exoglycosidic process. Conversely, we demonstrate that in faecal extracts from patients excreting glycosylated alpha 1-proteinase inhibitor, glycosidase activities, such as N-acetyl-beta-glucosaminidase (EC 3.2.1.30), alpha-mannosidase (EC 3.2.1.24) and particularly beta-galactosidase (EC 3.2.1.23), are strongly decreased. 3. Degradation of glycosidases by proteases could not explain the decreased glycosidase activity in these faecal extracts. 4. Our data suggest that a modification of the bacterial colonic flora (or of its metabolic activity) occurs in most patients with active Crohn's disease and could be responsible for an impaired colonic salvage of carbohydrates.

Acetylglucosaminidase↗

Effect of intrajejunal elemental diet perfusion on jejunal secretion of immunoglobulins, albumin, and hyaluronan in man.

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.

Adult↗

Increased pulmonary and intestinal permeability in Crohn's disease.

We tested the hypothesis that an increased epithelial permeability may affect sites other than the intestine in patients with Crohn's disease by simultaneously evaluating their pulmonary and intestinal permeability. Pulmonary and intestinal permeability were measured by clearance of inhaled technetium-99m diethylene triamine pentacetate (99mTc-DTPA) and by urinary recovery of chromium-51 ethylene diamine tetracetate respectively in 22 patients with Crohn's disease. The half time clearance of 99mTc-DTPA from lung to blood (t1/2LB) was decreased--that is pulmonary permeability increased--in the whole group of patients with Crohn's disease as compared with 13 controls (median 45.5 minutes (8-160) v 85 minutes (34-130) (p less than 0.003)). When analysed separately only patients with active Crohn's disease (n = 15) had a decreased t1/2 lung to blood v controls (42 minutes (8-160) v 85 minutes (34-130) (p less than 0.0025)). Among patients with active Crohn's disease, six were studied again when their disease was quiescent and their t1/2 lung to blood did not differ significantly. The intestinal permeability was increased in the whole group of Crohn's disease patients as compared with 15 controls (5.25% (1.2-24) v 1.7% (0.65-5.75) (p less than 0.0002)). When analysed separately both patients with active and inactive Crohn's disease had increased intestinal permeability v controls (8.1% (1.6-24) and 3.5% (1.2.9.2) v 1.7% (0.65-5.75)) (p less than 0.0001, p = 0.05 respectively). Six patients with active Crohn's disease were studied again when their disease was quiescent and their intestinal permeability decreased significantly p less than 0.04). Pulmonary permeability was increased in patients with Crohn's disease but was not greatly influenced by Crohn's disease activity as opposed to intestinal permeability. The mechanism of this increase is unknown, but may be related in some patients to the presence of an alveolitis.

Adolescent↗

Activated eosinophils in adult coeliac disease: evidence for a local release of major basic protein.

The eosinophil population is increased in the jejunal mucosa of patients with coeliac disease. Eosinophils may participate in the mucosal damage by releasing their granule components that have cytotoxic properties such as eosinophil cationic protein (ECP) and major basic protein (MBP). This study aimed to assess the presence of ECP and MBP in the jejunal mucosa of 10 adult patients with active coeliac disease who presented with villous flattening. Endoscopic jejunal biopsy specimens were obtained from macroscopically flattened jejunal mucosa and were processed for ultrastructural study and immunogold labelling using anti-MBP, anti-ECP, and anti-IgA antibodies. Numerous eosinophils were found in the upper part of the lamina propria and showed two types of morphological change: some were lytic and others exhibited ultrastructural signs of activation, containing altered granules with fading of the central core. IgA plasma cells were intermingled with eosinophils and had dense deposits on the external side of their cytoplasmic membrane. MBP was detected in central cores of granules but also diffusely in their matrix and in tight association with dense extracellular deposits. Conversely, ECP was detected only in the matrix of eosinophil granules. This study showed that numerous eosinophils are in an activated state in the mucosa of patients with active coeliac disease and release cytotoxic proteins such as MBP, which could contribute to the mucosal damage. The observation that eosinophils and IgA plasmocytes were closely associated in the mucosa supports a role for IgA in eosinophil recruitment and activation in coeliac disease.

Adolescent↗

Apudoma and subcorneal pustular dermatosis (Sneddon-Wilkinson disease).

The subcorneal pustular dermatosis (SPD) is a rare dermatosis. IgA monoclonal gammapathy is the most frequently associated disease with the SPD. We report a case of SPD in a patient with metastatic apudoma, an association not previously described. The rare nature of both diseases suggests that this association is not fortuitous.

Apudoma↗