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Biomedical subjects

M Mignon

Publications and source records attributed to M Mignon.

At least 73 records · Page 4Linked to original sources

The use of new somatostatin analogues, lanreotide and octastatin, in neuroendocrine gastro-intestinal tumours.

In an open phase III study, octastatin was given as a continuous subcutaneous (s.c.) infusion to 35 patients (mean age 62 years) with malignant neuroendocrine gastro-intestinal tumours and the carcinoid syndrome. The wash-out was often incomplete because of the advanced stage of disease. The starting dose of 1.5 mg/24 h was increased up to 3.0 mg/24 h at 3 months in some patients. The carcinoid syndrome disappeared in 20% of patients at 3 months and in 23% at 6 months, with 43 and 45% of patients, respectively, experiencing an improvement. The mean Karnovsky index increased by > 10% in 40% of patients at 3 and 6 months. Urinary 5-hydroxyindoleacetic acid (U-5-HIAA) levels at 3 months normalised in 1 patient, fell in 20% (by > 50%; p = 0.0021) and stabilised in 66%. The respective values at 6 months were 1, 17% (p = 0.023) and 60%. There was also a significant decrease in plasma chromogranin levels at 3 months (p = 0.042), which did not persist at 6 months. Tumour size fell (by > 50%) in 1 patient by 6 months but this patient had undergone chemoembolisation one month prior to the start of the study. Most patients had tumour size stabilisation (76 and 68%) or progression (20 and 24%) at 3 and 6 months, respectively. Dose escalation from 1.5 to 3.0 mg did not significantly improve clinical, biochemical or tumour responses. The treatment was well tolerated with minor adverse events. In an open pilot phase II study of 19 patients (mean age 58 years), patients were given high dose somatuline with a maintenance dose of 12,000 mg/day in 4 divided s.c. injections. U-5-HIAA, which was elevated in 13 patients with a mean of 444 mumol/day before the start, was reduced to 58% of baseline at 3 months, 68% at 6 months (p = 0.04), 66% at 9 months and 75% at 12 months (p = 0.14). P-chromogranin was elevated in 18 patients, with a mean of 5,300 micrograms/l before the start, and was reduced to 52, 55, 63 and 64% of the baseline at 3, 6 (p = 0.039), 9 and 12 (p = 0.013) months, respectively. In the responding patients, apoptosis was induced.

Adult↗

[Proctitis of diversion on an excluded rectum in patients with hemorrhagic rectocolitis].

OBJECTIVES: Diversion colitis is characterized by inflammatory lesions affecting colon or rectum excluded from the fecal stream for varied etiologies. These lesions may mimic both ulcerative colitis and Crohn's disease. The aim of our study was to examine the excluded rectum in patients with ulcerative colitis, and to study the evolution of the pathological lesions after ileo-rectal anastomosis. METHODS: Eighteen patients with ulcerative colitis treated by total colectomy before ileo-rectal anastomosis were studied. The pathological features i.e. glandular alteration, inflammatory infiltrate and mucosal ulceration or fissure, were studied during 3 periods: initial colectomy, excluded rectum at surgery for anastomosis and rectal biopsies after anastomosis. RESULTS: We observed on the excluded rectum a follicular lymphoid hyperplasia (18 cases), granulomas with giant cells (9 cases), mucosal fissures (9 cases). The inflammation extended to the submucosa in all cases and was occasionaly transmural. These lesions disappeared after the anastomosis and then seemed to be connected with the rectal diversion. CONCLUSIONS: The pathological changes of diversion proctitis that includes mucosal fissures, granulomas with giants cells or transmural inflammation, may lead to an erroneous diagnosis of Crohn's disease. The review of the previous colectomy is then mandatory to confirm the initial diagnosis of ulcerative colitis. These lesions disappear after anastomosis.

Adolescent↗

[Hamartoma of Brunner's glands. Report of two cases].

Two cases of duodenal hamartoma of the Brunner's glands are reported in a 41-year-old woman and a 61 year-old man. These polypoid lesions measured more than 4 cm and presented with haemorrhages. These forms are infrequent. Because of their atypical and sometimes severe clinical symptoms, and their endoscopic appearance, a diagnosis of malignancy could be done. Their pathological features demonstrate that these benign lesions have a dysembryoplastic pattern and can be called hamartomas.

Adult↗

Helicobacter pylori stimulates gastric acid secretion via platelet activating factor.

Platelet activating factor (PAF) is a phospholipid mediator known as potent ulcerogenic agent but its physiological role is still unknown in the gastrointestinal tract. Lyso PAF the immediate PAF procursor has no deleterious effect in the gastrointestinal tract. We have previously reported that lyso PAF is produced by gastric mucosa in basal condition and in response to gastrin in healthy men. Helicobacter pylori metabolises lyso PAF to produce PAF. The aim was to study the effect of PAF on the gastric acid secretion. Isolated rabbit glands were used as a model and acid secretion was assessed by (14C) Aminopyrine (AP) uptake. PAF and histamine stimulated AP accumulation time- and dose-dependently. PAF-induced AP accumulation was supressed by omeprazole and Fura 2. BN50727 a specific PAF antagonist inhibited PAF-induced AP accumulation. The presence of a PAF receptor transcript was investigated by reverse transcriptase polymerase chain reaction (RT-PCR) from total mRNA using two primers in which oligonucleotides were synthetized from the human leucocyte PAF receptor cDNA. A single RT-PCR band of the transcript with expected size was detected in the crude isolated cell fraction. These results and others from our laboratory suggest that PAF stimulates gastric acid secretion via specific receptor on the parietal cells and H. pylori produces PAF which may induce mucosal injury directly or indirectly via acid pathway.

Aminopyrine↗

Multicentre prospective controlled study of Barrett's oesophagus and colorectal adenomas. Groupe d'Etude de l'Oesophage de Barrett.

Previous studies have suggested that patients with Barrett's oesophagus may be at increased risk of colorectal neoplasia, though the association is disputed. In a multicentre prospective study we compared the prevalence of colorectal adenomas in patients with Barrett's oesophagus and controls. Barrett's oesophagus patients (n = 104) had histological confirmation of columnar epithelium extending more than 3 cm above the gastro-oesophageal junction. The 537 controls were patients with symptoms suggesting irritable bowel syndrome. No participant had a personal history of colonic neoplasm. Each patient underwent colonoscopy. Histologically proven adenomas were found in 26 Barrett's patients (25%) and 75 controls (14%). Three colorectal cancers were discovered in each group. The prevalence of adenomas was greater in the Barrett's oesophagus group than in the control group (p < 0.01) but the relation became non-significant after adjustment for age and sex and control for other known risk factors by a logistic regression model (odds ratio 1.4 [0.7-2.7]). The relative risk of adenoma was significantly higher in patients older than 59 than in younger patients (2.2 [1.3-3.5]) and in men than in women (3.4 [2.0-5.7]). Other factors contributing significantly to the risk of adenoma were a family history of colorectal cancer (2.3 [1.1-4.8]), rectal bleeding (2.1 [1.1-3.9]), previous colonic investigation (0.3 [0.1-0.7]), and complete as opposed to partial colonoscopy (6.4 [0.8-48.3]). We conclude that Barrett's oesophagus is not an independent risk factor for colorectal neoplasia and, therefore, is not, in itself an indication for colorectal screening.

Adenoma↗

[Diagnosis of colitis caused by cytomegalovirus infection in AIDS. Comparative value of total colonoscopy and rectosigmoidoscopy (apropos of 24 cases). AIDS GIT].

OBJECTIVES: To evaluate the respective diagnostic value of flexible rectosigmoidoscopy and colonoscopy in the cytomegalovirus colitis. METHODS: Twenty-four patients with AIDS were studied retrospectively. The entry criteria were: flexible rectosigmoidoscopy or colonoscopy, with 2 rectal and 2 caecal biopsies, presenting cytomegalovirus inclusions bodies linked to an inflammation at least on one colonic biopsy. RESULTS: Twenty-four patients had 29 colonoscopies. In 16 cases colonoscopy was performed to the caecum. The endoscopic findings of the 16 full colonoscopies were: 7 right colitis, 5 diffuse colitis, 2 bisegmentary colitis, 1 proctitis and 1 non endoscopic lesion. The histologic findings of the 16 full colonoscopies were: 5 cytomegalovirus inclusions on rectal biopsies and 16 on caecal biopsies. For the 13 incomplete colonoscopies, 11 had inclusions on rectal biopsies. So the flexible rectosigmoidoscopy was not sufficient to find inclusions 13 times out of 29. CONCLUSION: Our study indicates that in the cytomegalovirus colitis, inclusions predominate in the caecum, isolated right colitis exists and extra-colonic cytomegalovirus disease is not always found. For these reasons full colonoscopy is necessary for diagnosis in patients with normal flexible rectosigmoidoscopy.

AIDS-Related Opportunistic Infections↗

[Helicobacter pylori, a rediscovered bacterium. Implication in gastroduodenal diseases].

Helicobacter pylori is a microaerophilic bacterium initially found in the gastric antrum of patients with peptic ulcer disease. As a result, H. pylori is now believed to have a pathophysiologic role in gastritis as well as in peptic ulcer disease. Several recent studies showed that it may be associated with duodenal ulcer relapse and that eradication therapy using antibiotics may significantly decrease the ulcer recurrence rate in duodenal ulcer patients. Moreover, epidemiological studies suggest that it may increase the relative risk of carcinoma in the stomach and preliminary studies seem to indicate that some low-grade lymphoma in the stomach may regress after H. pylori eradication. Although the mechanisms by which H. pylori induces mucosal injury and/or neoplasm is not clearly understood, several modifications in gastric functions have been reported. The most specific way of detecting H. pylori in tissue is a combination of culture and histologic staining of mucosal biopsy specimens obtained by endoscopy. Rapid urease test, cytology and PCR procedures performed on biopsies may give rapid, sensitive and specific results. Breath test using 13C- or 14C-radiolabelled urea and serology tests are of particular importance when H. pylori diagnosis is needed via no invasive procedures. Helicobacter pylori is supposed to interact with G and D cells. Gastrin and somatostatin are synthetized and released from antral G and gastric D cells respectively. The gastric D cells are in close contact with either G and parietal cells. Gastrin stimulates gastric acid secretion and epithelial gastric cell proliferation (parietal and EC-L cells) while somatostatin inhibits these effects. Chronic gastritis is associated with fundic duodenal ulcer disease. In this situation, basal gastrin and meal- or bombesin-stimulated gastrin in the serum (especially gastrin G17) have been found to be higher in H. pylori positive than in negative patients. Moreover, gastrin decreases up to normal levels after eradication of H. pylori. The long term effect of a such hypergastrinemia is not so far established. The mechanism underlaying hormonal modification is poorly understood. Since no G/D cell ratio modification could be found after H. pylori eradication while the amount of somatostatin increases, one would suggest functional alteration of either G or D cells in the H. pylori-related chronic gastritis. The role of inflammatory mediators on the gastrin release and the processing of progastrin induced by the bacterium need further investigations.

Duodenal Diseases↗

Pouchitis--a poorly understood entity.

Pouchitis is an increasing drawback to patients who undergo ileal pouch-anal anastomosis for ulcerative colitis; complication overshadows the overall good functional results of this sphincter-saving operation. There is a need for cooperative, multicenter, and longitudinal studies of patients undergoing ileal pouch-anal anastomosis, to unravel the etiology and pathophysiology of pouchitis. Because of the absence of a mucosal inflammation before pouch construction, patients operated on for familial adenomatous polyposis are the perfect control group. Thus, it may be possible to elucidate and define the sequence that leads to pouchitis, including overgrowth of a colonic type flora, transformation of the histology to an epithelium with colonic features, an altered biochemical milieu in the lumen (volatile fatty acids, secondary bile acids), and changes in mucosal defense mechanisms.

Anal Canal↗

Regression of inflammatory pseudotumor of the liver under conservative therapy.

Inflammatory pseudotumors (IPT) of the liver are rare benign tumors of unknown origin. Most previously reported cases were initially misdiagnosed and treated surgically; thus, their course under medical treatment remains unclear. We report an additional case of hepatic IPT with a favorable outcome under medical treatment without surgical resection. New imaging and pathologic features of this disease are presented that may facilitate preoperative recognition and appropriate treatment.

Granuloma, Plasma Cell↗

Fundic argyrophil carcinoid tumor in a patient with sporadic-type Zollinger-Ellison syndrome.

In the Zollinger-Ellison syndrome, fundic argyrophil carcinoid tumors occur almost exclusively in the small subgroup of patients who also have multiple endocrine neoplasia type 1. In these patients, tumor development seems related to the same genetic alterations as those observed in other endocrine tumors related to multiple endocrine neoplasia type 1. We report here the second detailed case of a patient with sporadic Zollinger-Ellison syndrome who developed an argyrophil carcinoid tumor in nonatrophic fundic mucosa, suggesting that chronic hypergastrinemia may lead to fundic carcinoid development in nongenetically predisposed patients.

Aged↗

Localization of gastrinomas by endoscopic ultrasonography in patients with Zollinger-Ellison syndrome.

BACKGROUND: Preoperative localization of gastrinomas by current imaging techniques such as computed tomography (CT) scan and angiography is still difficult because of the small size of tumor(s) in most patients undergoing operation. This study evaluated the diagnostic value of endoscopic ultrasonography. METHODS: Twenty-two patients presenting with Zollinger-Ellison syndrome underwent exploratory laparotomy after preoperative attempts to identify the gastrinoma(s) by CT scan, upper gastrointestinal endoscopy, and endoscopic ultrasonography. Surgery included intraoperative ultrasonography and duodenal transillumination in all cases. The sensitivity and specificity of imaging techniques were then evaluated. RESULTS: At least one tumor was found in 19 patients (four had two tumors and one had multiple tumors). Duodenal, lymph node, and pancreatic gastrinomas were found in 42%, 38%, and 17% of the patients, respectively. Sensitivity of endoscopic ultrasonography was 50% for duodenal wall tumors (conventional endoscopy, 40%), 75% for pancreatic tumors (CT scan, 25%), and 62.5% for tumoral lymph nodes (CT scan, 0%). The specificity of all techniques was excellent. Correct diagnosis was made by endoscopic ultrasonography alone in 41% of the patients. The combination of conventional endoscopy and endoscopic ultrasonography provided correct diagnosis in 60% of the patients. CONCLUSIONS: Endoscopic ultrasonography should be considered as a first-choice imaging technique for preoperative detection of gastrinomas. Although small duodenal gastrinomas are still obviously difficult to detect, an accurate exploration of the pancreatic area was provided by this technique.

Adult↗

Quantitative analysis of the immune cells in the anal mucosa.

The prevalence of anoperineal diseases, i.e. sexual transmitted infections, is increasing particularly in AIDS, a fact which is likely due to the alteration of mucosal immunity. However, no data were available on normal anal status. In order to study anal immunity in man, we characterized lymphocytes subtypes and Langerhans' cells (LC) using quantitative morphometric analysis and immunohistochemistry. Anal normal mucosal samples obtained from surgical specimens of 45 patients (30 suffering from hemorrhoids and 15 from fissurations) were analyzed. Immunohistochemistry was performed on frozen sections with antibodies recognizing CD1a (LC), CD3 (T lymphocytes), CD4 (T4), CD8 (T8) and CD22 (B-lymphocytes). Immunostained cells were counted per square millimeter of mucosal epithelium. The surface of CD1a cells was measured using a computerized software program and a percentage of CD1a immunostained area was calculated in comparison to the whole mucosal surface. LC and T-Lymphocytes were found in the squamous epithelium in all analyzed samples. The mean values of LC number were 84.13 +/- 9.6 and 64.77 +/- 9.8 in hemorroid- and fissure-patients, respectively. The mean values of LC area (% of CD1a stained area over total mucosal surface) were 3.89 +/- 0.44 and 4.84 +/- 0.64, respectively. In the two groups, the number of intraepithelial CD8 lymphocytes was higher than that of CD4 lymphocytes. These data suggest for the first time that anal mucosa could be considered as a part of MALT system.

Adult↗

Evaluation of transferrin-binding protein 2 within the transferrin-binding protein complex as a potential antigen for future meningococcal vaccines.

Because the meningococcal transferrin receptor was shown to elicit bactericidal and protective antibodies in laboratory animals, we undertook a study of the protective role of each of the polypeptides within the Tbp1-Tbp2 complex. We developed a procedure to purify from Neisseria meningitidis B16B6 the two proteins in milligram amounts and raised specific antisera in rabbits and mice. Only antisera specific for Tbp2 displayed bactericidal activity against the parent strain. Mice immunized with purified Tbp2 survived a lethal challenge to a similar degree as animals immunized with the Tbp1-Tbp2 complex, demonstrating that Tbp2 played an important role in the protective activity observed with the complex. Both Tbp1- and Tbp2-specific antisera inhibited transferrin binding to the purified receptor in a solid-phase binding assay, suggesting that the antibodies were able to interact with the Tbp1 molecule only when it was removed from its membrane environment. Finally, Tbp2-specific immunoglobulins were able to lower the growth rate of the meningococci when human transferrin was their sole iron source. Therefore, in all four different systems tested, Tbp2 or antibodies specific for Tbp2 displayed biological characteristics close to those of the Tbp1-Tbp2 complex. This suggests that Tbp2 plays an important role in the protective activity of the complex, eliciting antibodies that are not only bactericidal but also inhibitory for meningococcal growth.

Animals↗

M or M-like protein gene polymorphisms in human group G streptococci.

Many group G streptococci (GGS) isolated from infected humans (but not from animal sources) express M or M-like proteins with biological, immunochemical, and genetic features similar to those of group A streptococci (GAS). To further elucidate the recently proposed M-like protein gene (emmL gene) polymorphisms in GGS, Southern blots of genomic DNAs from 38 epidemiologically unrelated GGS strains isolated from human specimens and 12 GGS strains recovered from animal sources were hybridized with oligonucleotide probes designed to specifically detect GAS M class I and M class II M protein (emm) genes. All human-associated GGS strains showed DNA homology to the GAS M class I emm gene probe, whereas no hybridization was found with DNA from any of the animal-associated strains. The emmL genes from all human isolates were amplified by PCR, and the complete sequence of the emmL gene of the Rebecca Lancefield grouping strain D166B was determined. Again, this gene exhibited the structural features typical for emm genes of M class I GAS. The 5' regions of the PCR-amplified emmL genes of the remaining 37 human GGS strains were sequenced. This region showed a sequence diversity similar to that known for GAS emm genes. When strains whose N-terminal emmL gene sequences showed a homology of > 95% were defined as belonging to one genetic type, 30 strains were segregated into six distinct genetic types, whereas the remaining 8 strains each exhibited a unique emmL gene sequence. A high degree of homology between the N-terminal emmL gene segments of six GGS strains and the corresponding regions of either the emm12 or the emm57 gene of GAS was found, suggesting a horizontal gene transfer between strains of these species of beta-hemolytic streptococci. Besides a further understanding of the evolution of GGS emmL genes, the observed emmL gene polymorphisms in GGS could provide the basis for a molecular subspecies delineation of strains and offers the potential of typing GGS for epidemiological purposes.

Amino Acid Sequence↗