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Biomedical subjects

R Modigliani

Publications and source records attributed to R Modigliani.

At least 19 recordsLinked to original sources

Characterization of two human monoclonal IgM antibodies that recognize nuclear lamins.

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.

Animals

Oral intraepidermal IgA pustulosis and Crohn's disease.

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.

Crohn Disease

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

[Digestive lymphomatous polyposis].

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.

Adult

[Treatment of hemorrhagic rectocolitis].

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.

Colectomy

[Treatment of Crohn disease].

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.

Aminosalicylic Acids

[Celiac disease and collagenous colitis. A fortuitous association].

We report the cases of two patients with coeliac disease in whom chronic diarrhoea persisted in spite of strict adherence to a gluten free-diet and regression of intestinal villous atrophy. Collagenous colitis was evidenced in both patients. Six cases of such association have already been described. Because of subepithelial deposition of collagen in the colon of collagenous colitis and in the small intestine of coeliac disease, it has been suggested that the colonic collagen band might reflect a toxic effect of gluten on colonic epithelium. However, thickening of the colonic collagen band during strict gluten free-diet, as observed in one of our cases, is not in favour of this hypothesis.

Adult

Clinical, biological, and endoscopic picture of attacks of Crohn's disease. Evolution on prednisolone. Groupe d'Etude Thérapeutique des Affections Inflammatoires Digestives.

One hundred forty-two patients with active colonic or ileocolonic Crohn's disease were included in a multicenter prospective study. Data collection included 28 clinical, biological, and endoscopic items; the latter were recorded according to a standardized colonoscopic protocol; a previously validated endoscopic index of severity was calculated. Oral prednisolone (1 mg/kg body wt per day) was started and maintained until clinical remission and for at least 3 and at most 7 wk. A second clinical biological and endoscopic evaluation was then performed. At initial colonoscopy, mucosal lesions were, by decreasing order of frequency, superficial ulcerations, deep ulcerations, mucosal edema, erythema, pseudopolyps, aphthoid ulcers, ulcerated stenosis, and nonulcerated stenosis (93%, 74%, 48%, 44%, 41%, 35%, 10%, 8%, and 2% of cases, respectively). No correlation was found between the clinical activity index and any of the endoscopical data (lesion frequency and surface, endoscopic severity index). Ninety-two percent of patients underwent clinical remission within 7 wk of treatment. None of the 28 clinical biological and endoscopical items collected just before treatment could predict clinical response to steroids. Only 38 of the 131 patients in clinical remission were also in endoscopic remission. In conclusion, (a) the description and severity of colonoscopic lesions in active Crohn's disease have been quantified; (b) no correlation exists between clinical severity and nature, surface, or severity of endoscopic lesions; (c) Oral prednisolone (1 mg/kg body wt per day) induces a clinical remission in 92% of patients within 7 wk; (d) resistance to steroids cannot be predicted from the data collected before treatment onset; and (e) only 29% of patients in clinical remission also achieve endoscopic remission.

Adult

[Treatment of Crohn's disease with azathioprine or 6-mercaptopurine. Retrospective study of 126 cases].

Over the past 15 years (1974-1989), 126 patients with Crohn's disease received azathioprine (n = 123) or 6-mercaptopurine (n = 3). Seven patients were lost of follow-up during the first month and were not analyzed. Among the 119 patients analyzed (52 men, 67 women, mean age 31.6 years), the median duration of treatment was 9.1 months (range: 8 days to 15 years). Most of the 109 patients with active disease at the beginning of the immunosuppressive therapy were either steroid-dependent (n = 63) or steroid-resistant (n = 23); 19 had frequent relapses and/or extensive involvement of the gastrointestinal tract; 4 had severe perianal disease. Among these 109 patients, 25.4, 51, 60.4 and 64.4 percent were in clinical remission at 3, 6, 9 and 12 months (life-table analysis) respectively. There was no difference in outcome of patients with colonic, ileocolonic or small intestinal involvement. Steroid-resistant patients fared better than steroid-dependent patients (81 percent vs 59 percent of remission within the first year; p less than 0.001). In the 62 patients with quiescent disease treated with azathioprine or 6-mercaptopurine, previous remission had been achieved with immunosuppressive therapy in 52, 8 were treated after a bowel resection which was assumed to be curative; 2 had achieved remission after total parenteral nutrition. In these patients, the percentages of relapse were 15.3 at the end of the first year and 20.3 at the end of the second year. Among the 8 patients treated with azathioprine after bowel resection, only one relapse occurred 1.5 months after surgery. Nineteen percent of the patients had adverse reactions that required discontinuation of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis

[Physiopathology of diarrhea].

Diarrhoea is defined as the daily excretion of faecal water in increased amounts. Several mechanisms may result in diarrhoea. They are: (1) increase in fluid and ions load which may exceed the maximum capacity of intestinal reabsorption; this is the "volumogenic" diarrhoea observed in Zollinger-Ellison syndrome; (2) accelerated gastrointestinal transit, notably through the colon, as in the so-called "diarrhée motrice" due to increased colonic motility; (3) osmotic diarrhoea due to ingestion of nonabsorbable solutes, as in malabsorption syndromes; (4) secretory diarrhoea with disorder of NaCl transport in the intestine as its main abnormality; this diarrhoea may be of bacterial, endocrine or other origin; (5) diarrhoea consecutive to morphological abnormalities of the small bowel and/or colon; it is often due to several of the above mechanisms, to which must be added exudation of blood, mucosities and proteins in the intestine.

Colon

Symptomatic, radionuclide and therapeutic assessment of chronic idiopathic dyspepsia. A double-blind placebo-controlled evaluation of cisapride.

Twenty-eight patients with chronic idiopathic dyspepsia defined by the presence of chronic unexplained symptoms suggestive of gastric stasis and directly related to food ingestion were included in this prospective study. Gastric emptying of the liquid and solid phases of a meal was quantified by a dual-isotope method, and symptoms were evaluated by a diary and a visual analog scale. Delay in gastric emptying was evidenced in 59% of the dyspeptic patients; it occurred with liquids in more cases than solids. Quantitative and qualitative evaluation of symptoms was of no practical value in predicting the presence of objective stasis. The dyspeptic patients were included in a double-blind randomized controlled trial of cisapride, a new gastrokinetic drug devoid of central antiemetic effects. After six weeks of cisapride treatment, all patients with initially abnormal gastric emptying rates for liquids, and all but one for solids returned to normal ranges, and significant differences between cisapride and placebo groups were observed for half emptying times of both solids (136 +/- 16 min vs 227 +/- 32 min; P less than 0.02) and liquids (61 +/- 4 min vs 132 +/- 37 min; P less than 0.01). Cisapride also significantly improved dyspeptic symptom scores at weeks 3 and 6 of treatment as compared to those measured before treatment. Nevertheless, the decrease in global diary score was significantly higher than that seen with placebo at week 3 (-16 +/- 6 vs -1 +/- 9; P less than 0.05), but not at week 6 (-18 +/- 5 vs -10 +/- 8).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Development and validation of an endoscopic index of the severity for Crohn's disease: a prospective multicentre study. Groupe d'Etudes Thérapeutiques des Affections Inflammatoires du Tube Digestif (GETAID).

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.

Colonoscopy