[Anomalies of the immune system in chronic inflammatory bowel diseases].
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Biomedical subjects
Publications and source records attributed to R Modigliani.
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OBJECTIVES AND METHODS: The performances and the clinical significance of a simplified version of the 75SeHCAT test which measures ileal absorption of bile salts were assessed in 23 healthy subjects and 106 patients. Corporeal retention of the marker was measured using an uncollimated gamma-camera. RESULTS: In healthy subjects, the 75SeHCAT retention was lower in the group of 9 with an osmotic diarrhoea induced by a PEG solution than in the group of 14 tested in normal conditions (22 +/- 4% vs 44 +/- 4%; P < 0.01). The reproducibility of the measure was good (r = 0.93; P < 0.001). The sensibility and specificity of the test for the diagnosis of ileal involvement were 79% and 90% respectively. Bile acid malabsorption was evidenced in 38% of patients with functional diarrhoea (59% and 28% in patients with and without previous cholecystectomy respectively; P < 0.02). In patients with fonctional diarrhoea, a correlation was evidenced between the orofaecal transit time and the 75SeHCAT retention (r = 0.66; P < 0.001) and cholestyramine improved diarrhoea in 8 out of 11 patients with 75SeHCAT malabsorption and in 2 out of 5 patients with normal test. These results show that the 75SeHCAT test is accurate and that bile acid malabsorption, frequently evidenced in functional diarrhoea, is correlated with an acceleration of intestinal transit.
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BACKGROUND: Mesalamine provides a new therapeutic approach in treating Crohn's disease. METHODS: To assess the efficacy and safety of slow-release mesalamine (Pentasa; Ferring AS, Vanløse, Denmark) 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 a 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 ongoing 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. CONCLUSIONS: 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.
Eighteen patients infected with human immunodeficiency virus and with chronic unexplained diarrhea were prospectively studied to investigate the prevalence and clinical and biologic features of intestinal microsporidiosis. All patients underwent extensive evaluation for bacterial, viral, and parasitic pathogens. Enterocytozoon bieneusi was found in 9 patients (50%; 95% confidence interval, 27-73) in stools and duodenal and jejunal biopsies. In 8 patients, it was the sole pathogen found. Other pathogens were also isolated from the intestinal tracts of 4 patients, but diarrhea remained unexplained in 6. Patients with intestinal microsporidiosis had significantly lower mean Karnofsky scores (69.4 vs. 85.5, P = .009), CD4 cell counts (18.6 vs. 209.8/microL, P = .02), and D-xylose absorption tests (0.13 vs. 0.36 g/L, P < .001) than did patients without intestinal microsporidiosis. Intestinal microsporidiosis appears to be a frequent cause of unexplained chronic diarrhea in patients with AIDS and is associated with diminished D-xylose absorption.
We studied two patients with a leukaemic T cell lymphoma who presented with a marked increase in blood eosinophilia. To investigate the mechanism of the eosinophilia, supernatants of peripheral blood cells containing more than 80% lymphoma cells were tested by biological assays for the presence of colony stimulating factors (CSF). In one case supernatants stimulated the growth of granulocyte-macrophage (GM), erythroid and eosinophil colonies. These effects were neutralized by anti-GM-CSF antibodies; anti-IL5 antibodies slightly decreased eosinophil colony formation. Supernatants derived from the second patient cells stimulated the same lineages. Neutralizing experiments demonstrated that in addition to GM-CSF it contained interleukin 3 (IL-3) and interleukin 5 (IL-5). In agreement with the biological data, RNA studies using the polymerase chain reaction showed that cells from the first patient expressed GM-CSF transcripts; IL-5 transcripts were also detected in very low amounts. GM-CSF, IL-3 and IL-5 transcripts were detected in cells from the second patient. Thus eosinophilia associated with some T cell lymphoma is likely due to secretion of different combinations of cytokines by malignant cells.
Ulcerative colitis can only be cured by surgery. Colonic perforation and rectocolic cancer are absolute indications for surgery. Severe attacks of ulcerative colitis are classically managed for 5 days by intensive medical treatment, including intravenous and rectal corticosteroids. Colectomy must be performed if this treatment fails. Although not universally accepted, endoscopy is of great help to select patients needing early surgery. Finally, chronic continuous and cortico-dependent forms will obviously benefit from surgery. Proctocolectomy with ileal pouch-anal anastomosis clearly makes certain surgical decisions somewhat easier.
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.
Using immunofluorescence and immunoblotting techniques, we have identified monoclonal IgM lambda from two patients that are specific for lamins A and C and lamin B, respectively. Lamins A, B, and C are peripheral membrane proteins of the nuclear envelope with structural similarities to cytoplasmic intermediate filament proteins. When studied by indirect immunofluorescence on rat tissues, the serum containing anti-lamin B IgM stained smooth and striated muscles in addition to nuclear envelopes. Lamin B antibodies affinity purified from this serum were able to label muscle cells, suggesting that lamin B shares an epitope(s) with an unidentified muscular component(s). Since in an enzyme-linked immunosorbent assay there was no reactivity with a panel of proteins which are frequent targets of "natural" antibodies, these monoclonal IgM appear to belong to the rare category of IgM that possess a restricted specificity.
A case is reported of a 60-year-old woman with Crohn's disease who developed recurrent oral blisters and erosions. The histopathology of the buccal mucosa showed intraepidermal bullae and clefts with an intense accumulation of neutrophils in the epithelium. Direct immunofluorescence revealed intercellular IgA predominantly in the basal and suprabasal layers and in one biopsy concurrent deposits of IgG. No circulating autoantibodies were detected.
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.
We report 7 prospectively followed cases of lymphomatous polyposis of the gastrointestinal tract. They were characterized by multiple polypoid lesions affecting several segments of the gastrointestinal tract always involving the colon and the rectum. An ileocecal mass was present in 4 cases. Regional lymph node involvement was constant. Peripheral lymphadenopathy was frequent (5 cases out of 7), as was other extra-digestive extension to the bone marrow (4 cases out of 7) and cavum (3 cases out of 7). The histopathological aspect was that of a small cleaved cells (working formulation) or centrocytic (Kiel classification) non-Hodgkin's lymphoma. The peculiar morphology and phenotype of the tumoral B-lymphocytes suggest their possible follicle marginal zone origin. Lymphomatous polyposis bore a rapidly fatal prognosis in every case (mean survival 20 months). This study of seven patients together with the 20 well-documented cases of the literature confirms the existence of lymphomatous polyposis as a distinctive clinicopathological entity among gastrointestinal non-Hodgkin's lymphoma.
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Ulcerative colitis (UC) is a chronic inflammatory disease usually localized to the mucosa of the rectum and colon. Its cause remains unknown. A few fundamental notions underlie the therapeutic approach: (1) UC generally evolves by acute episodes separated by remissions, and the therapeutic indications depend on the severity and periodicity of these acute episodes; (2) although UC is a usually benign disease it may kill in two circumstances: when a severe (or complicated) acute episode is operated belatedly, or when cancer of the colon develops; (3) the present medical treatment only has a suspensive effect on the disease; the maintenance treatment must be taken for life; (4) only total proctocolectomy can provide complete cure, and until recently this procedure required permanent ileostomy. The recently introduced ileo-anal anastomosis (after total colectomy and rectal mucosectomy) gives the same results and enable the natural anus to be spared.
Crohn's disease is a chronic inflammatory disease of the bowel for which there is no curative treatment. The purpose of treatment is to reduce mortality to the absolute minimum and to give the patients a normal quality of life. Acute episodes of low severity are treated with sulfasalazine and its most recent derivatives such as 5-aminosalicylate. More severe episodes require oral corticosteroid therapy which, when prescribed in adequate doses, results in clinical remission in over 90% of the cases. To this must be added parenteral nutrition in patients with very severe symptoms or when a major nutritional deficit is present. During remissions, a maintenance treatment with 5-aminosalicylate or azathioprine is justified when the acute episodes are frequent and/or severe. These continuous chronic forms require prolonged low-dose corticosteroid therapy or azathioprine. Artificial nutrition is the best way of treating corticosteroid-resistant episodes. In children, corticosteroids must be avoided as much as possible, and low-flow rate enteral nutrition is often used as primary treatment of salicylate-resistant episodes. The surgical treatment of Crohn's disease consists of resection of the lesions with anastomosis or ileostomy in case of total proctocolectomy. Following resection-anastomosis, the cumulative relapse rate is about 50% ten years after surgery; it is lower after colostomy and proctocolectomy. Surgery is indicated in case of complications (abscesses, stenosis, fistulae, perforation) and when the disease does not respond to a well-conducted medical treatment. Specialized teams including physicians, surgeons, proctologists and specialists in nutrition are essential to a correct treatment of Crohn's disease.
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