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Biomedical subjects

M Mignon

Publications and source records attributed to M Mignon.

At least 163 records · Page 9Linked to original sources
PubMed1990

[pH gradient support and antacid action of gastroesophageal coating agents. In vitro pharmacologic study using a model of "the artificial stomach"].

The effects of gastroesophageal mucosal coating agents could be related to a) the decrease of aggressive contents of gastric juice and/or b) the presence of a pH gradient between intraluminal (IL) contents and mucosa. Antacid capacities of Gaviscon and Topaal, containing sodium alginate or alginic acid, respectively, were measured using the "artificial stomach" model. This model, reproducing two major gastric dynamic functions, secretion and gastric emptying, allows to evaluate the pH variations in the IL contents and at its surface, by a double pH metric recording. Experiments were performed when drugs to be tested were added either to 100 ml of human gastric juice (100 mmol/l or 88 mmol/l with biliary reflux) or to 100 ml of 0.1 N HCl, without and with 1 percent meat extract. Simulated secretion was represented by a 3 ml/min flux of either 0.1 N HCl or gastric juice and "gastric emptying" fluxes varied from 1.5, 3.0 to 4.5 ml/min. When 0.1 N HCl solution was used, the pH levels at the surface of IL contents were close to pH 3.0 when intragastric pH reached pH 1.0 independently of "gastric" emptying flux variations. In the presence of proteins or biliary reflux material, these pH levels were higher, close to pH 4.5 and persisted for a longer time. Antacid activity was calculated as the resistance to acidification of the IL contents, as the amount of H+ ions consumed after addition of antacid to recover initial pH, i.e. 37 and 22 mmol in human gastric juice, between 37 and 17.5 mmol in 0.1 N HCl for Gaviscon and Topaal, according to emptying fluxes.(ABSTRACT TRUNCATED AT 250 WORDS)

Alginates↗
PubMed1990

New approach for the in vitro evaluation of antacids.

Evidence is given that the in vitro evaluation of antacids has been incomplete, not regarding physiopathological conditions. As a consequence arbitrary antacid potency classifications were introduced and in clinical practice high dosages of antacid drugs were prescribed. The main reason is that the in vitro evaluation procedures used did not take into account the actual conditions of gastric acid secretion. The proposed methods allow to assess antacid activity under conditions similar to those during gastric secretion. "Pharmacologically", the capacity of binding H+ ions in acid milieu can be quantified and the antacid mechanism can be characterized. "Therapeutical efficacy" might be analysed under acid conditions taking into account gastric intraluminal flux variations by using the "artificial stomach" model. This procedure also allows to evaluate the influence of gastric protein content on antacid activity and to simulate the actual gastric conditions by using human gastric juice as gastric content and as simulated "secretion". The antacid-induced resistance to acidification largely corresponds to the therapeutical antacid activity. Data obtained with aluminum containing antacids are presented.

Antacids↗
PubMed1990

[Intermittent treatment or preventive treatment of recurrence in duodenal ulcer disease? A controlled, double-blind study with 150 mg ranitidine daily for one year].

This 1-year study compared two pragmatic strategies in long-term management of duodenal ulcer: continuous treatment with ranitidine 150 mg after dinner and treatment of duodenal ulcer attacks with ranitidine 300 mg and placebo in the interval. A multicentric, randomized double-blind study was conducted in 399 patients, 197 in the ranitidine group and 202 in the placebo group. Efficacy was judged by the prevalence of ulcer-pain recurrences; secondary criteria were the prevalence of endoscopic recurrences, complications and the number of facultative visits, hospitalizations and days off work related to duodenal ulcer disease. Both groups were similar with regard to main epidemiologic features and number of drop-outs (10.5 percent). Fifty-two patients were withdrawn for symptomatic or endoscopic relapses: 6 in the ranitidine group, 46 in the placebo group (p less than 0.05). Sixty-six percent of the patients remained asymptomatic at one year in the ranitidine group versus 33 percent in the placebo group (p less than 0.001). Seventeen patients with ranitidine (8.6 percent) and 59 with placebo (29.2 percent) experienced at least one endoscopic recurrence (p less than 0.05). In the placebo group, 8 complications were observed (bleeding = 5, duodenal stenosis = 3), and none in the ranitidine group (p less than 0.005). Patients with ranitidine had significantly less facultative visits and endoscopies, number of days off work, and hospitalizations (p less than 0.05). Tolerance was good (5 percent side-effects, all minor) and identical in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Assessment of antacid characteristics of drugs containing a combination of aluminium and magnesium salts using the "artificial stomach" model.

Antacid characteristics of three drugs containing aluminium and magnesium salts (combination of clay with aluminium and magnesium hydroxides, aluminium and magnesium hydroxide mixture and hydrotalcite) have been studied in a dynamic situation simulated by the "artificial stomach" model, simultaneously taking into account both gastric fluxes, a constant secretory flux and variable emptying fluxes. Therapeutic doses of the drugs were added 1. to 100 ml of 0.1 N HCl, without or with 1% or 5% meat extract, and 2. 100 ml of pooled human gastric juice (96 mmol/l, pH 1.1). In addition, antacid activity of 0.5 g aluminium and magnesium hydroxides, taken alone or in combination, were evaluated when added to 100 ml of 0.1 N HCl. In aqueous HCl solution or in human gastric juice, the three antacid drugs exhibited 1. a neutralising activity characterised by pH-rise and 2. a buffering capacity close to pH 3.8. In addition, hydrotalcite exhibited also buffering capacity at pH 1.2. The antacid-induced capacity, expressed as H+ mmol, to recover initial pH were very similar, indicating that antacid physiochemical properties are similar in HCl solution or in gastric juice. H+ consumption depended upon emptying fluxes. The same antacid characteristics were observed when antacids were mixed with 1% meat extract while 5% meat extract resulted in a modification of antacid characteristics. Therefore the antacid capacities of respective mixtures were of smaller magnitude (50-60%) than the sum of the activities of antacids plus meat extracts.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum Hydroxide↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

[Anorexia nervosa: absence of sensitivity to nutritional protein markers. Study of 23 patients and comparison to a paired group with colonic Crohn's disease].

One of the most important therapeutic goal in anorexia nervosa is to define with the patient a body weight to obtain. To do so, objective criteria are needed. For this purpose, we studied in a longitudinal way, 9 nutritional parameters in 23 patients with anorexia nervosa, as compared with 23 age - and sex - matched patients with Crohn's disease: body weight, tricep's skinfolds, mid-arm muscle circumferences; serum albumin, prealbumin, transferrin, hemoglobin, cholesterol; urinary creatinine and calcium, magnesium, zinc and copper serum levels and urinary outputs. Despite losses of body weight, of lean body mass and of fatty mass higher in patients with anorexia nervosa than in those with Crohn's disease, the former had higher nutritional protein's serum levels than the latter. These nutritional protein markers were not in anorexia nervosa different from normal values. In anorexia patients, zinc and copper serum levels and urinary outputs were very low. This study suggests that nutritional protein markers of hepatic synthesis are not sensitive markers for malnutrition evaluation and can not be used to follow renutrition efficacy.

Adult↗
PubMed1989

[Experimental models in studying gastric secretion in dogs: innervated pouch, denervated pouch, cervical esophagostomy. Execution, monitoring, use].

Different surgical models are used in the dog for studying gastric secretion: gastric fistula, denervated Heidenhain pouch, innervated Amdrup pouch and cervical esophagostomy. The surgical procedures are described as well as the care and the monitoring allowing long-term survival of the animals. The association of gastric fistula - Heidenhain pouch has been assessed 30 times and 8 times with cervical esophagostomy. The death-rate was been 7% and the morbidity 24%. Three dogs were provided with an Amdrup pouch. Calibration of the animals allowed the acid and pepsin secreting dose-response to be platted and translation according to lineweaver-Burk or Dowd and Riggs is used to calculate the efficient dose (ED 50) and the maximal response (maxR). Pharmacological or physiological effects might be analyzed in regard to the modification of these parameters in response to a pharmacological agonist or antagonist substance. Some physiological studies could be made using sham-feeding on dogs fitted with a cervical esophagostomy.

Animals↗