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Biomedical subjects

S Bonfils

Publications and source records attributed to S Bonfils.

At least 37 records · Page 2Linked to original sources

Effect of the histamine-1 antagonist astemizole alone or with omeprazole on rat gastric mucosa.

The stimulation of acid secretion by gastrin may in the rat be explained solely by gastrin-induced histamine release. This study was done to examine whether histamine could mediate the general trophic effect of gastrin on the oxyntic mucosa, by using a long-acting selective histamine-1 antagonist (astemizole) alone or with omeprazole-induced hypergastrinaemia for 90 days in female Sprague-Dawley rats. At day 90, isolated vascularly perfused rat stomachs were prepared to study maximal gastrin- and histamine-stimulated acid and pepsinogen outputs and maximal gastrin-stimulated histamine release. Oxyntic mucosa morphometry, mucosal histamine and pepsinogen contents, and plasma gastrin and histamine levels were also determined. For the first time, omeprazole has been found to inhibit gastric emptying and to increase plasma histamine. As compared with controls, astemizole alone did not influence plasma gastrin, increased plasma histamine in only some rats, and gave a slight increase in all other variables. Together with omeprazole, it further increased variables already stimulated by omeprazole. Thus, mucosal thickness, histamine concentration, and chief-cell density in oxyntic mucosa were significantly higher in astemizole/omeprazole-treated rats than in omeprazole-treated rats. Gastrin-stimulated histamine release was increased in both astemizole- and omeprazole-treated rats. For all rats plasma histamine was significantly correlated with plasma gastrin and with numerical fundic argyrophil cell density. In conclusion, the present study confirms the trophic effect of gastrin and shows a slight trophic effect of astemizole on the oxyntic mucosa. It also shows that plasma histamine may reflect the argyrophil cell density in the oxyntic mucosa and that omeprazole inhibits gastric emptying.

Animals↗

[Idiopathic ulcerative proctitis. Clinical presentation and endoscopic outcome].

Endoscopic information was obtained for 52 patients with ulcerative proctitis (23 F, 29 H) seen during a ten-year period. The median follow-up was 68 +/- 8 months. During the first referral period (38 patients experienced a first attack), endoscopic particularities were available: inflammation involved the anal mucosa above the dental line (n = 16), the whole circumference of rectal mucosa (n = 19) or the anterior wall exclusively (n = 33). The upper limit was 12.2 +/- 0.6 cm from the anal verge. Inflammatory lesions were higher in circumferencial conditions, when patients were older (late onset disease) but sex and ethnic state did not influence results of endoscopic presentation. Exulcerations or superficial ulcers were visualized in 16 and spontaneous bleeding in 43. Forty-five patients achieved clinical accuracy after 9.4 +/- 1 ms, but 32 only a complete endoscopic remission. Mean number of relapses was 3.6 +/- 0.4; 13 patients experienced a single attack. During relapses, inflammation was stable in 11 of 38 patients. Extension to the rectum in rectosigmoid junction, and sigmoid and above by 6, 14, and 7 patients respectively. After 5 years follow-up, the cumulative risk of further extension was 37 percent and 13 percent, respectively. Low abdominal pain, an family history of ulcerative colitis, and high inflammatory lesions at referral were significantly associated with a higher risk of extension. Cancer did not occur and not surgery was necessary during the follow-up. Idiopathic proctitis is perhaps at the "benign end" of the spectrum of ulcerative colitis. Nevertheless, its endoscopic particularities should be noticed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Plasma pharmacokinetics of roxatidine in the healthy man: correlation with gastric antisecretory effect].

Inhibitory effects of roxatidine acetate upon human gastric secretion have been shown to be dose-related after oral administration. In order to correlate this effect with drug pharmacokinetics, blood concentration of the active metabolite, roxatidine, was assessed in 10 healthy volunteers, each receiving in random order 75, 150, 300, 600 mg of roxatidine acetate and placebo. Blood was drawn for roxatidine measurement at T 0 (time of drug intake) T 75, 90, 120, 150, 210, 240 and 300 min. Meal-induced gastric secretion was studied by intragastric titration (IGT) at 15 min intervals, from T 150 to T 240. Mean peak of blood concentration occurred at T 150 with significant correlation with the administered dosage. Gastric secretion inhibition over the 90 min of IGT correlated with peak concentration exclusively for the subpopulation with peak occurrence at T 150. Beyond the peak, decrease in roxatidine concentrations was slow, as expected from a known 6-h half-life. However, overall results showed that mean blood concentration was correlated with gastric secretion inhibition from T 180 on. The last IGT sample also correlated with the peak. Interpretation of these results would be different whether roxatidine concentration variations are appreciated as exhibiting a significant decrease or not. Infusion studies of roxatidine would be a valuable technique for further analysis and comparison of blood-concentration/efficacy relationships as compared with other H2-antagonists.

Adult↗

Gastric endocrine cell behavior in Zollinger-Ellison patients upon long-term potent antisecretory treatment.

Serum gastrin and gastric endocrine cell numerical densities were examined in 22 patients with long-standing Zollinger-Ellison syndrome who were receiving either ranitidine, omeprazole, or other antisecretory drugs (SMS 201-995 or pirenzepine with or without ranitidine) for long periods of time. Fifteen patients had iterative biopsies. Twenty-one subjects with normal endoscopy, serum gastrin, and acid secretion served as controls. Individual fundic argyrophil cell density was above the highest control value in 77% of the patients, whatever the treatment. Argyrophil cell densities tended to be higher in women than in men. During the survey, fundic carcinoids developed in one ranitidine- and in one omeprazole-treated patient. Fundic argyrophil cell densities were correlated with serum gastrin levels (r' = 0.730, p less than 0.001). Antral somatostatin cell density was not modified in any patients as compared with controls, nor was antral gastrin cell density except in omeprazole-treated patients. In these patients, gastrin cell density and gastrin to somatostatin cell ratio were significantly higher than in all other patients or controls. Such increases may indicate true gastrin cell hyperplasia in relation to drug-induced profound acid inhibition.

Adult↗

Gastrin processing in primary culture of gastrinoma cells.

There is a general agreement on the cell specificity of gastrin processing. In order to investigate this processing in Zollinger-Ellison (ZE) patients, we have studied in two primary gastrinoma cultures (one from a pancreatic tumor, the other from a liver metastasis) the proportion of progastrin fragments using immunochemical and immunohistological methods. In tumor extracts as well as in sera, the predominant gastrin form differed between the two patients (i.e. being G17 and G34, respectively). In the two gastrinoma cultures, RIA determinations and electron microscopic observations indicated that the proportion of progastrin increased with time while that of G17 and G34 decreased. On the other hand, as the culture time extended, an increasing proportion of nonimmunostained secretory granules was observed suggesting the presence of other gastrin precursors (e.g. Gly-extended progastrin). From these findings, we suggest that gastrinoma culture cells could be a valuable tool in the biochemical approach to gastrin processing in ZE tumors.

Cells, Cultured↗

Immunohistochemical characterization of gastrinomas with antibodies specific to different fragments of progastrin.

The characterization of the tumors and their metastasis in patients with the Zollinger-Ellison syndrome is currently based on the immunohistochemical identification of gastrin cells. However, sometimes tumoral cells fail to react with common C-terminal gastrin antibodies. In order to clarify this failure, we carried out morphologic, morphometric and immunocytochemical analyses performed on light and electron microscope levels of 6 pancreatic and 1 metastatic gastrinomas, using antibodies raised against various sequences of human progastrin. On the basis, in light microscopy, of qualitative analysis of immunostaining within cells and of immunostained cell numbers, gastrin 34 residue seemed to be the prominent form in 2 of the tumor tissues, G-17 in 1 tumor which was not responsive with C terminus progastrin and N terminus G-34 antisera, and progastrin in the metastatic tissue that did not contain typical gastrin (G-like) cells. Two tumors failed to react with all antisera used. At the electron microscope level, immunogold staining revealed that progastrin was present only in the progranules and gastrin 34 in both progranules and intermediate granules. Quantitative studies performed on 3 tumors showed that, within a given tumoral cell, about 25 percent of progranules contained progastrin while 75 percent contained gastrin 34. We concluded that different forms of gastrin can be immunodetected in a gastrinoma tissue, depending on the regions, and that the distribution of progastrin fragments is variable from tumor to tumor. So, specific antibodies to different fragments of progastrin may help to the characterization of gastrinomas.

Antibodies↗

[Familial colonic cancer (Lynch's syndrome) and bile duct cancer. Study of 2 cases].

The authors describe two cases of bile duct carcinoma affecting two patients with hereditary non polyposis colorectal carcinoma (Lynch's syndrome). These two cases were observed in 14 families composed of 283 persons, 58 of whom were affected by hereditary non polyposis colorectal cancer and 15 by gynecological carcinomas. Bile duct carcinoma can therefore be associated with Lynch's syndrome but seems less frequent than observed in familial polyposis or Gardner's syndrome.

Adult↗

[Sigmoid motility stimulated by luminal distention. Changes in the motility response in constipation by the slowing down of left colonic transit].

The aim of our study was to develop a new technique of sigmoid manometry using standardized luminal distensions and to compare patterns of colonic motility following distension in normal subjects and in constipated patients. Eight subjects without colonic disturbances and 8 constipated patients with delayed transit time of the left colon as shown by radiopaque markers were investigated. Sigmoid motor activity was recorded by measuring pressure in a distending latex balloon placed at 25 cm from the anus. Inflations were maintained during 250 s and separated by 60 s recovery periods of deflation. Volumes of air (V) were increased until the patient reported abdominal pain (VMT). For each distension level, the resistance to distension of the bowel wall evaluated by the baseline adaptative pressure (P) and the contractile activity (A) quantified by planimetry of the active contractile activity (A) quantified by planimetry of the active contraction waves superimposed to P were assessed. In normal subjects, VMT was 147 +/- 9 ml. P increased linearly with V (p less than 0.03) up to 4,336 +/- 876 Pa. A increased with V until VMT/2 reached the maximum of 389 +/- 72 Pa*; for higher volumes A decreased significantly with to 166 +/- 46 Pa for VMT. Reference to controls, the constipated patients had a decreased VMT (61 +/- 4 ml). P increase at VMT (5,084 +/- 753 Pa) and A maximal value (387 +/- 176 Pa) were not different.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Relation of the kinetics of the antisecretory effect and kinetics of blood concentration in man. Comparing cimetidine and ranitidine].

The time course of antisecretory effects of ranitidine and cimetidine and their relationship to plasma concentration were studied in 4 healthy volunteers. Placebo, cimetidine (266 mg) or ranitidine (100 mg) were infused during one hour preceding the 90 minute assessment of food-stimulated gastric acid secretion (intragastric titration); cimetidine and ranitidine blood levels and gastric acid outputs were measured at 15 min intervals. For each test a significant (p less than or equal to 0.01) correlation was found between concentration and effect. The half-life effect of ranitidine (t1/2 E) was significantly (p less than or equal to 0.05) greater than t1/2 E of cimetidine whereas their plasma half-lives (t1/2) were similar. The ratio t1/2 E/t1/2 was significantly (p less than or equal to 0.05) lower with cimetidine than with ranitidine. Explanations for this discrepancy are analyzed according to various hypotheses. The determination of t1/2 E seems to be a good approach to the duration of action of H2-antagonists. Our results show that the ratio t1/2 E/t1/2 and the t1/2 E might be important pharmacokinetic parameters to compare various H2-receptor antagonists.

Adult↗