Morphologic features of large bowel biopsies in combined small and large bowel transplantations could predict clinical rejection.
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Publications and source records attributed to M Peuchmaur.
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OBJECTIVE: Recent studies on the management of human fetal gastroschisis have produced two major findings: (1) there is an inflammatory response in the amniotic fluid of these fetuses, and (2) amniotic fluid exchange designed to disrupt the inflammatory loop seems to have a favorable impact on the immediate and late outcome of these early operated neonates. To test this hypothesis, we used serial amniotic fluid exchanges in a model of gastroschisis developed in the ewe. METHODS: Gastroschisis was created at midgestation in 21 lamb fetuses by an in utero technique. Saline was amnioinfused in some fetuses every 10 days to term. Fetuses were sacrificed on day 145 by cesarean section. Extra-abdominal bowels with fibrous peel were processed for histologic examination. Comparisons were done between fetuses without gastroschisis (controls), fetuses with gastroschisis and amnioinfusion, and fetuses with gastroschisis without amnioinfusion. RESULTS: Of 21 fetuses operated, 8 died in utero or were stillborn; 5 were not amnioinfused, and 8 underwent amnioinfusion. Thickness of bowel muscularis (micrometer) was 92.6 +/- 20.2 for controls, 126.2 +/- 21 for the amnioinfused fetuses, and 182.8 +/- 58.3 for the nonamnioinfused fetuses (p = 0.001). The same significant results were obtained for thickness of serous fibrosis (p = 0.02) and plasma cell infiltration (p = 0.015). CONCLUSIONS: We have created a model of gastroschisis suitable for experimentation in the fetal sheep. Our amnioinfusion data in this model indicate a clear improvement of the deleterious process. This finding correlates well with recent data on amnioinfusion as a therapeutic approach to human gastroschisis.
From November 1994 to November 1998, 20 children (2.5 to 14 years) received a jejunoileal graft alone (SBTx; n = 10) or in combination with the liver (SBLTx; n = 10 and/or the right colon (5 SBTx). Indications were intractable diarrhea of infancy (n = 8), short bowel syndrome (n = 6), extensive Hirschsprung disease (n = 4), and chronic intestinal pseudoobstruction (n = 2). Immunosuppression included tacrolimus, methylprednisolone, and azathioprine. Current follow-up ranges from 6 to 54 months. Five patients died (3 SBTx) within the first 2 months. Acute liver rejection occurred in 5 patients during the first 2 months. Sixteen episodes of intestinal rejection during the first 3 months in 11 patients (8 in 4 SBTx) were successfully treated in all but 3 by increasing tacrolimus dose and/or a 3-day methyprednisolone bolus or required antilymphoglobulins in 3 cases. Surgical complications occurred 8 times after SBLTx and 3 after SBTx. Infectious complications were more frequent in SBLTx recipients. Reversible Epstein-Barr virus-related posttransplant lymphoproliferative disease occurred in 3 recipients. Five presented cytomegalovirus infection. The SB graft was removed in 5 recipients (3 chronic rejection). All patients were started with oral and/or enteral feeding from the 7th postoperative day by using either normal food or protein hydrolysate diet. Currently, 10 of 11 children (8 SBLTx) achieved digestive autonomy after 5 to 30 weeks. All recipients gained weight; however, growth velocity remained reduced during the first 6 months because of the steroid therapy. Overall graft and patient survival is higher after SBLTx. Intestinal transplantation is indicated for patients with permanent intestinal failure. However, because parenteral nutrition is generally well tolerated, even for long periods, each indication for transplantation must be weighed carefully in terms of risk and quality of life.
UNLABELLED: The peroxisome proliferator-activated receptor (PPAR) gamma is highly expressed in the colon mucosa. In vitro, it regulates inflammation. AIM: To evaluate the anti-inflammatory functions of PPARgamma agonist during a trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice. METHODS: Colitis was induced in Balb/c mice after intra-rectal administration of TNBS. The intensity of inflammation was assessed 2 and 5 days after colitis induction by macroscopic and histologic scores and by the quantification of colon myeloperoxidase (MPO), IL-1B and TNFalpha mRNA concentrations. The therapeutic role of PPARgamma agonist given by oral gavage was assessed in preventive and treatment modes. RESULTS: TNBS induced severe macroscopic and histologic lesions, with high mucosal MPO, IL-1B and TNFalpha mRNA concentrations. PPARgamma agonist given preventively or in treatment mode allowed a significant decrease of macroscopic and histologic scores through a normalization of MPO, IL-1B and TNFalpha mRNA concentrations. CONCLUSION: PPARgamma agonist decreases the intensity of TNBS induced colitis through normalization of IL-1B and TNFalpha expression. PPARgamma agonists may be proposed as new therapeutic agents in inflammatory bowel diseases.
We recently demonstrated that IL-2 is produced by reactive T cells in CD25-positive malignant lymphomas (ML). Using in situ hybridization, we investigated IL-6 mRNA expression in these CD25-positive ML. The ML tested included 9 anaplastic large cell lymphomas and 3 B-diffuse large cell lymphomas. Five CD25-negative ML were studied as controls. We show that IL-6 producing cells are present in all these ML. The density of positive cells was heterogeneous from case to case. However 3 cases of CD25-positive ML showed a dramatically higher density of IL-6 producing cells (70, 50, 43 producing cells per 10,000 cells, respectively) as compared to the other 9 cases of CD25-positive ML (mean 6.03 +/- 2.1 per 10,000). Morphological and topographical data suggested that several types of cells including fibroblasts, lymphocytes, macrophages and endothelial cells may synthesize IL-6. A combination of immunohistochemistry and in situ hybridization showed that reactive T cells and endothelial cells express the IL-6 gene whereas CD30-positive ML cells do not express this gene. Previous studies showed that IL-6 was capable to induce IL-2 receptor expression as well as production of IL-2 and stimulation of lymphomatous cells growth. Our present results indicate that the paracrine production of this cytokine may play a role in the proliferation of malignant lymphomas.
Macrophage infiltration is a constant feature of human virus-infected tissues. However, the in situ functional status of these cells remains undetermined. In order to document an activation of macrophages in virus-infected tissues, the expression of IL-1 beta and IL-6 genes was analyzed using in situ hybridization. Several tissues were studied, as well as infections induced by different viruses: lymph nodes infected by HIV-1 (9 cases) or EBV (one case), lungs infected by CMV (5 cases) or adenovirus (1 case), livers infected by HBV, either chronically (2 cases) or acutely (7 cases presenting a fulminant hepatitis). With the exception of fulminant HBV hepatitis, IL-1 beta and IL-6 genes were expressed in all cases. IL-1 beta and IL-6 genes were usually coordinately regulated, as cells containing IL-1 beta or IL-6 mRNA were present in identical amounts and displayed a similar distribution. Analysis of the location and the morphology of monokine gene-expressing cells indicated that both small macrophages and endothelial cells expressed IL-1 beta and IL-6 genes. However, neither tingible body macrophages present in lymph node follicles nor Kupffer cells expressed these genes at a detectable level. Infected cells themselves were also negative for monokine gene expression. These findings indicate that expression of IL-1 beta and IL-6 genes by reactive cells may play a role in viral spreading limitation as well as virus-induced tissue damage.
Twenty-four malignant mesenchymal tumour specimens were analysed for human multidrug resistance (MDRI) gene transcript levels using Northern and slot blot techniques. The presence of P-glycoprotein was assessed in 12 of the 24 samples by immunohistochemistry using the monoclonal antibody (MAb) C219. Increased MDRI transcript levels were found in 2 (8.3%), while, using immunohistochemistry, 2 samples were positive and 3 faintly positive (41.6%). Overall, elevated P-glycoprotein or MDRI transcript levels were found in tumours of 6 patients, 3 of whom are dead. The relationship to MDRI expression and subsequent resistance to chemotherapy has to be established.