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Biomedical subjects

M Cerf

Publications and source records attributed to M Cerf.

At least 19 recordsLinked to original sources

Plasma kallikrein localisation in human blood vessels.

Immunoreactive plasma kallikrein/prekallikrein was detected in the endothelial cells and the smooth muscle cells of the arteries examined. The most intense overall immunolabelling of plasma kallikrein/prekallikrein was visualized in the medium to small size arteries. The endothelial cells of the pulmonary artery and the smooth muscle cells of the supracallosal artery showed the highest intensity of plasma kallikrein/prekallikrein labelling. The least defined labelling occurred in the tunica adventitia. The renal vein was the only blood vessel that showed no trace of immunoreactive plasma kallikrein/prekallikrein. The question arises as to the mechanisms that could be involved in the in vivo conversion of plasma kallikrein/prekallikrein into the active enzymatic molecule. The experiments indicate that a bacterial elastase cleaves the Arg371-Ile372 scissile bond within a disulphide bridge of the prekallikrein molecule. This is the bond that is cleaved also during activation of prekallikrein by trypsin-like proteinases. Functionally, the endogenous activation of plasma prekallikrein is of considerable importance, both in the regulation of blood flow and blood pressure and in the causation of septic shock. The incidental finding at histology, of patchy atheromatous disease in the coronary, vertebral and supracallosal arteries, assisted in elucidating the role of plasma kallikrein/prekallikrein in the commonest disease affecting human blood vessels. Intense labelling for plasma kallikrein was observed in the endothelial cells, foamy macrophages, inflammatory cells and fibroblasts within the thickened intima of the plaque as well as in smooth muscle cells of the underlying tunica media. The intense immunolabelling of plasma kallikrein/prekallikrein in these regions suggest that these may be induced by atheromatous disease.

Arteries↗

Prevalence and pathogenicity of Clostridium difficile in hospitalized patients. A French multicenter study.

BACKGROUND: Although Clostridium difficile is the main agent responsible for nosocomial diarrhea in adults, its prevalence in stool cultures sent to hospital microbiology laboratories is not clearly established. OBJECTIVES: To determine the prevalence of C difficile in inpatient stools sent to hospital microbiology laboratories and to assess the relationship between serotypes and toxigenicity of the strains isolated and the clinical data. METHODS: From January 18, 1993, to July 31, 1993, the presence of C difficile was systematically investigated in a case-control study on 3921 stool samples sent for stool culture to 11 French hospital microbiology laboratories. The prevalence of C difficile in this population (cases) was compared with that of a group of 229 random hospital controls matched for age, department, and length of stay (controls). Stool culture from controls was requested by the laboratory although not prescribed by the clinical staff. Serotype and toxigenesis of the strains isolated were compared. RESULTS: The overall prevalence of C difficile in the cases was twice the prevalence in the controls (9.7% vs 4.8%; P < .001) and was approximately 4 times as high in diarrheal stools (ie, soft or liquid) as in normally formed stools from controls (11.5% vs 3.3%; P < .001). The strains isolated from diarrheal stools were more frequently toxigenic than those isolated from normally formed stools. Serogroup D was never toxigenic, and its proportion was statistically greater in the controls than in the cases (45% vs 18%; chi 2 = 5.2; P < .05). Conversely, serogroup C was isolated only from the cases. Clostridium difficile was mainly found in older patients ( > 65 years), suffering from a severe disabling disease, who had been treated with antibiotics and hospitalized for more than 1 week in long-stay wards or in intensive care. CONCLUSIONS: This multicenter period prevalence study clearly supports the hypothesis of a common role of C difficile in infectious diarrhea in hospitalized patients. Disease associated with C difficile should therefore be systematically evaluated in diarrheal stools from inpatients.

Anti-Bacterial Agents↗

Lymphocytic and collagenous colitis: an immunohistochemical study.

OBJECTIVES: An increase of intraepithelial lymphocytes (IEL) is commonly found in lymphocytic colitis (LC) and collagenous colitis (CC), and has also been observed in the colonic mucosa of some patients with celiac disease or celiac-like disease. Thus, a similar mechanism could play a role in these apparently different entities. The aim of this work was to determine the phenotype of IEL and of lamina propria lymphocytes in the setting of LC and CC. METHODS: Biopsies were taken from all segments of the large bowel and from the ileon of eight patients with CC, four patients with LC, and 10 controls. An immunohistochemical study using monoclonal antibodies directed against IEL, T-cells, helper T-cells, suppressor/cytotoxic T-cells, HLA DR antigens, T-cell-bearing T-cell receptor (TcR) alpha beta, and TcR gamma delta was carried out. RESULTS: There was an increased in mean numbers of IELs in both LC and CC, with significantly more CD 8 IELs than CD 4 IELs. Most IELs were bearing TcR alpha beta; TcR gamma delta-bearing cells were not increased in CC or LC. CD 4+ helper T-cells predominated in the lamina propria. Epithelial cells of colonic mucosa abnormally expressed HLA DR antigens. There were no significant differences between findings in LC and CC. CONCLUSION: This study suggests that the immune abnormalities are similar in LC and CC and that a MHC-restricted immune mechanism could be involved in both diseases. Evidence for this includes: 1) the accumulation of CD 4+ T-cells within the lamina propria, 2) epithelial damage closely related to the increase of CD 8 TcR alpha beta IELs, and 3) abnormal class II MHC molecule expression on epithelial cells of colonic mucosa. Furthermore, the results suggest that the putative immune mechanisms underlying LC or CC are probably different from those that are incriminated in celiac disease.

Adult↗

[Whipple disease: a single or multiple origin?].

After having been considered as an essentially digestive disease, Whipple's disease has appeared more and more to be a multivisceral disease with two main characteristics: on one hand Whipple's disease yields a diffuse infiltration of tissues by abnormal macrophages without any other inflammatory reaction; on the other hand, aspects of microbial invasion by intra or extracellular unique rod-shaped Gram+bacteria are found. This unusual pathological complex has alternatively been considered as suggestive of an immunological defect or as a very unusual type of bacterial infection. Though recent studies support the hypothesis of a primary microbial infection due to a hitherto undescribed bacterium (Tropheryma whippelii) or more or less related bacteria belonging to the actinomycetes family, they do not totally exclude a primary or acquired impairment of antigen processing by macrophages. Speculations about this fascinating pathophysiological model and about its optimal therapeutic modalities are not likely to reach a conclusion in the near future.

Bacterial Infections↗

Mechanisms of decreased food intake during weight loss in adult Crohn's disease patients without obvious malabsorption.

Because weight loss is common in colonic Crohn's disease and is poorly correlated with disease activity, we analyzed food intake in 63 patients without malabsorption, 30 patients with weight loss (9.2 +/- 4.2 kg), and 33 patients without weight loss. Energy and protein intakes were lower in patients with weight loss than in those with stable weight (P < 0.01). In the former group, food restrictions were more numerous (P < 0.01) and visual analog scales showed less hunger, decreased appetite, and fewer sensations of pleasure related to eating, as compared with the other group (P < 0.01). Food intake reduction was also related to depressive mood and medical advice. However, there was no difference between groups in fecal energy wasting and resting energy expenditure. Weight loss in Crohn's disease may be due to a decrease in food intake rather than to an increase in energy cost of the disease. Thus, focus of attention on the diet is crucial to prevent malnutrition.

Adult↗

[Chronic small intestine obstructions].

Chronic small bowel obstruction may be related either to disordered motility or to progressive chronic stenoses. Disordered motility (or intestinal pseudo-obstruction) is the consequence for muscular and/or intrinsic nerve impairment with 2 main types, one of which is primary (including so-called visceral myopathies and visceral neuropathies), the other one being secondary (generally due to systemic, or sometimes immunologic disease). Chronic stenoses have a different pathophysiology and occur in the setting of chronic inflammatory bowel disease or of systemic diseases such as vasculities. Chronic stenoses lead to intestinal stasis and in fine to mechanical obstruction. In any case, chronic obstruction poses difficult diagnostic and therapeutic problems. Management calls for tight medico-surgical cooperation. Atypical surgical operations may be warranted, and specific, sometimes aggressive medical care is mandatory. Moreover the nutritional consequences of chronic small bowel obstruction may become highly disabling due to alimentary restriction, disordered transit, bacterial overgrowth and malabsorption. In this setting nutritional support should be a matter of prime concern.

Chronic Disease↗

[Increase of resting energy expenditure during flare-ups in Crohn disease].

Crohn's disease is an inflammatory process commonly characterized by phases of flare-up. Weight loss and malnutrition are prominent features in the course of the disease, especially during acute episodes. It is therefore important to define energy needs. Curiously, resting energy expenditure (REE) has rarely been studied in Crohn's disease, and never in relation with the activity of the disease. We therefore determined REE together with body composition (fat free mass, FFM), Crohn's disease activity index (CDAI) and plasma acute phase proteins in 70 patients: during flare-up in 41 and during clinical remission (CDAI < 150) in 29. We found an increase in REE in patients with active disease (CDAI > 150), as compared with patients in remission, when REE was expressed as a function of FFM: 31.7 +/- 2.7 versus 29.4 +/- 3.3 kcal/kg FFM/day (P < 0.01). The mean REE/FFM was 8% higher during flare-up than during remission, and was correlated to both clinical (CDAI; P = 0.011) and biological inflammatory activity indices (C reactive protein, P = 0.018; orosomucoid, P = 0.024). In some patients, the REE was in the normal range, despite an increase in REE/FFM, because of a decrease in FFM due to hypermetabolism. In 8 patients treated successfully by total parenteral nutrition for a massive flare-up, REE/FFM was increased before TPN (36.6 +/- 3.0 kcal/kg/day), and decreased after 4 weeks of TPN (31.4 +/- 1.8 kcal/kg/day; P < 0.001), returning within normal values in 7 patients.

Adult↗

[Acute diarrhea in adults in a Parisian district. Clinical, bacteriologic endoscopic and histologic aspects. Study of 52 cases].

From 1985 through 1988, 52 patients aged 16 to 85 years and referred for acute diarrhea underwent routine clinical, microbiological, endoscopic and histopathological examinations. Enteropathogens were isolated in 50 percent of patients, mostly from stool samples rather than from biopsy samples, though results were sometimes dissociated. Significantly lower digestive endoscopic abnormalities were seen in 60 percent of patients. Upper gastrointestinal endoscopy was not contributive. Rectal and colonic biopsies showed histological abnormalities in nearly all cases half of which were polymorphonuclear infiltrates and crypt abscesses. Glandular distortion was not found. An analysis of clinical, endoscopic and histological data showed that major abnormalities were mostly, but not constantly, related to infections due to enteroinvasive bacteria. As in other studies, a high rate of negative stool cultures was observed. Based on these results, we suggest to perform either further and more sophisticated microbiological investigations, or to conduct a routine search for viral infections whose incidence, among adult patients with acute diarrhea, is actually unknown.

Acute Disease↗