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Biomedical subjects

S Bonfils

Publications and source records attributed to S Bonfils.

At least 73 records · Page 4Linked to original sources

The antigastrinic effect of a phenothiazine (LM 24056) prevents gastric secretory activity of histamine.

Gastric antisecretory phenothiazine LM 24056 inhibited acid and pepsin responses to feeding in dogs. Administered perorally two hours before feeding, LM 24056 reduced significantly the secretory responses to combinations of feeding either with antramine, a natural histamine derivate, or with synthetic histamine. LM 24056 reduced circulating gastrin levels (p less than 0.01 and p less than 0.001) and gastrin responses to feeding (p less than 0.01) without modifying neither circulating histamine concentrations nor histamine responses to feeding. The residual acid and pepsin secretions were closely related to gastrin reduction and endogenous or exogenous histamine, by themselves, seemed to be unable to recover the levels of secretory responses observed in response to feeding alone or in combination with antramine or histamine. These data favour a new scheme of gastric secretion regulation where gastrin would be the last step for stimulating parietal and chief cells. LM 24056 by reducing circulating gastrin prevents stimulatory effect of exogenous or feeding-released endogenous histamine. Histamine would not be thus the final common mediator for gastric secretion.

Animals↗

Antral gastrin- and somatostatin-producing cells and intraluminal peptide secretion in normal subjects and duodenal ulcer patients with and without vagotomy.

The behaviour of gastrin (G) cells and somatostatin (D) cells in endoscopic antral biopsies and that of intraluminal gastrin (ILG) and somatostatin (ILS) release in the gastric juice were investigated in three groups of patients: control subjects, duodenal ulcer (DU) patients and DU patients treated by a superselective vagotomy (SSV). G and D cell densities were correlated in the three groups of subjects. The G/D cell ratio was significantly increased in SSV patients (P less than 0.001) as compared to control and DU patients. No correlation was found between gastrin or somatostatin cell densities and basal intraluminal levels of the two peptides. ILG output was significantly higher in DU patients than in control or SSV patients (P less than 0.001). ILS output was also higher in DU patients than in controls (P less than 0.001) and in SSV patients (P less than 0.05). It was also significantly augmented in SSV (P less than 0.001) as compared to control patients. ILG and ILS concentrations were only correlated in controls. Within each of the three groups of subjects, ILG and ILS release varied in function of the gastric juice pH. Our results emphasize the necessity to consider the intragastric pH as well as the physiological or pathological state to study intraluminal peptides in man.

Adolescent↗

Intragastric pH profile during acute respiratory failure in patients with chronic obstructive pulmonary disease. Effect of ranitidine and enteral feeding.

The ability of H2 receptor antagonists and continuous enteral alimentation to maintain high intragastric pH in patients with chronic obstructive pulmonary disease (COPD) requiring mechanical ventilation was evaluated by continuously monitoring intragastric pH prior to and following sequential addition of ranitidine or continuous enteral alimentation (or both) to their therapeutic regimen. Prior to therapy, intragastric pH was less than 4.0 for 75 +/- 10 percent of the time, but never less than 1.0. Nevertheless, this moderate gastric acidity was associated with evidence of mucosal injury. Ranitidine failed to continuously maintain a high intragastric pH (pH less than 4.0 for 35 +/- 11 percent of the time; p greater than 0.2 compared to patients treated with placebo). Following administration of continuous enteral alimentation, intragastric pH fell, and ranitidine therapy only partially blocked this increase in gastric acidity induced by continuous enteral alimentation. We conclude that without treatment, patients with COPD who have acute respiratory failure may develop gastric mucosal injury despite the presence of only moderate intragastric acidity; however, ranitidine and continuous enteral alimentation are not effective in maintaining a high intragastric pH.

Acute Disease↗

[Histologic aspect of the human gastric mucosa: relation to gastrin and somatostatin cells and the intraluminal secretion of these peptides].

Fifty-eight subjects including controls, patients with duodenal ulcer, non-operated or treated with a superselective vagotomy underwent endoscopic fundic and antral biopsies. Histologic classification of the two mucosae was performed. We examined the relationship between the histologic grade of gastritis in the two mucosae, then between the histologic aspect of the antral mucosa and antral gastrin-and somatostatin-cell densities, the basal intraluminal secretion of gastrin and somatostatin. There was a significant correlation between the histologic aspect of fundic or antral mucosa and the age of patients, except in the case of vagotomized patients. Fundic and antral histologic patterns were also correlated in each patient, except for vagotomized. Gastrin and somatostatin cell densities showed no variation in function of the degree of inflammation of non atrophic gastritis. These cell densities showed a tendency to decrease in atrophic gastritis, especially when intestinal metaplasia was present. Intraluminal gastrin secretion was increased in patients with mild atrophic gastritis (p less than 0.05 to p less than 0.02) in comparison with those whose histology was roughly normal. It was also increased in severe atrophic gastritis. The highest intraluminal secretion of somatostatin was observed in patients with mild atrophic gastritis while this secretion fell noticeably in those showing severe atrophic gastritis, as compared to the other groups. This work seems to suggest a relationship between intraluminal peptides and the evolution of gastritis. While results are still preliminary, they do not indicate that these peptides, thus released, play any pathophysiologic role.

Adolescent↗

Acute and chronic 24-hour gastric pH and pharmacokinetic studies with a long acting antisecretory drug (40749 RP) in peptic ulcer.

The purpose of this work was to compare the effects of a long acting antisecretory drug on 24-h gastric acidity after acute and chronic administration and to correlate the results observed with modifications of pharmacokinetic parameters. 40749 RP is a carbothioamide derivative antisecretory drug with a non anti H2, non anticholinergic mechanism of action. Eleven patients with an endoscopically proven duodenal ulcer received 100 mg of 40749 RP at 8 PM for 3 wk and thereafter a placebo for an additional 3 wk study period. At the end of the active drug treatment period all patients but one had healed. Continuous 24-h gastric pH recordings performed after the first and the last dose of 40749 RP showed a strong and yet still increasing acid inhibition, nine patients being nearly achlorhydric (i. e. pH greater than 3) during night at the end of treatment. Variations of acid inhibition between the start and the end of treatment were significantly correlated with modifications of pharmacokinetic parameters. Eight days after discontinuation of 40749 RP, basal acid secretion remained strongly inhibited. However at the end of the placebo period, endoscopy showed ulcer relapse in 4 patients (previously resistant to H2-blockers). These results confirmed that 40749 RP is a powerful and very long-acting antisecretory drug. They showed that the antisecretory effects of a long-acting drug should be assessed in conditions of chronic administration when therapeutic dose and regimen are to be determined.

Adult↗

Epithelial cell proliferation in human fundic and antral mucosae. Influence of superselective vagotomy and relationship with gastritis.

Epithelial cell proliferation in the fundic and antral mucosae was studied in 19 duodenal ulcer patients, 11 patients having undergone fundic superselective vagotomy for duodenal ulcer, and 10 controls. This was achieved through in vitro incorporation of tritiated thymidine in mucosal biopsies and radioautography. Except for increased fundic mucosal height, duodenal ulcer patients did not differ from controls for all parameters studied. In vagotomized patients, as compared to the other two groups, the labeling index was significantly enhanced in the innervated antral mucosa where atrophic gastritis developed, but there was no change in the labeling index and no worsening of mucosal inflammation in the denervated fundic mucosa. The only abnormality in the latter was a striking expansion, towards the surface, of the proliferative area within the fundic pit. The labeling indices and the degree of gastritis in gastric mucosae are significantly correlated in control and duodenal ulcer patients. After superselective vagotomy, this correlation still existed in antral mucosa (r = 0.88, P less than 0.001) but not in fundic mucosa. If findings in antral mucosa, after superselective vagotomy, seemed related to gastritis lesions, those in fundic mucosa were not and may indicate an alteration due to the vagotomy per se.

Adolescent↗

A comparative evaluation of secretin bolus and secretin infusion as secretin provocation tests in the Zollinger-Ellison syndrome.

GIH secretin bolus (2 CU/kg) and infusion (3 CU/kg/h) have been randomly compared in 9 ZES patients and 10 age-matched DU patients. Serum gastrin and gastric acid variations were studied before and after either mode of secretin administration in the same individuals. Plasma secretin modifications were monitored in parallel. In both ZES and DU, secretin bolus and infusion induced similar gastrin responses (maximal changes and integrated responses). However, secretin infusion had a greater effect on acid output than bolus: larger inhibition in DU and larger increase in ZES. The additive diagnostic value of gastric acid secretion study during a secretin provocation test, as already reported, favors the use of 3 CU/kg/h secretin infusion over that of 2 CU/kg secretin bolus.

Administration, Oral↗

Antramine (antral histamine) antagonizes somatostatin inhibition on endogenous gastrin-induced gastric secretion. A new hypothesis for the role of histamine in gastric secretion regulation.

The effects of antramine, an antral histamine (AH), and of synthetic histamine (SH) on acid, pepsin, and gastrin responses to meals alone or in combination with somatostatin were studied in dogs equipped with a Heidenhain pouch. Food-induced acid secretion was potentiated by AH and only slightly increased by SH. Pepsin secretion was increased by AH and decreased by SH. Both AH and SH suppressed the inhibitory activity of somatostatin on food-induced secretion. AH potentiated gastrin response to feeding but decreased it when somatostatin was added to the meal. Since acid secretion was unrelated to gastrin response, it would appear that the secretory effects of AH involve a direct action on secreting cells, itself based on the suppression of somatostatin inhibition. Gastric secretion is probably related to gastrin efficacy on secreting cells, which would result from the antagonistic effects of somatostatin and AH. These data suggest an alternative hypothesis concerning the role of histamine in the control of gastric secretion.

Amino Acids↗

[Efficacy of ranitidine and cimetidine in the treatment of gastric or duodenal ulcer resistant to an initial treatment with cimetidine. Multicenter controlled therapeutic trial].

In a controlled clinical trial conducted in 28 centers, 354 ambulatory patients with a cimetidine-resistant duodenal or gastric ulcer (at least six weeks of treatment at a dose of 1 g/day) confirmed by endoscopy were allocated at random to either ranitidine or cimetidine treatment: 166 patients received cimetidine (1.6 g/day in 4 oral doses), and 188, ranitidine (0.3 g/day in 2 oral doses). The two groups differed significantly with regard to sex and history of gastrointestinal hemorrhage but not with regard to age, weight, history of peptic disease, history of perforated ulcer, duodenal/gastric ulcer ratio, number of smokers and alcohol consumers. The criterion of effectiveness was endoscopic healing of the ulcer after six weeks of treatment; in case of doubt, vital staining with methyl blue was performed. A significant difference was observed between the results of the two treatments in the duodenal group (p less than 0.05) but not in the gastric group, the healing rates being respectively 71 p. 100 and 65 p. 100 with ranitidine, and 59 p. 100 and 44 p. 100 with cimetidine. Twelve patients developed side-effects with a highly significant difference between the two groups: 11 patients under cimetidine and one patient under ranitidine (p less than 0.001). These results show the effectiveness of ranitidine as a complementary treatment in cimetidine-resistant peptic ulcers of duodenal location.

Adult↗

[Gastrointestinal manifestations of AIDS].

We studied 26 cases of digestive manifestation in AIDS. The 26 patients were divided into two different epidemiological groups: 13 homosexual men, constituted the first group; no homosexual patient was in the second group which included 6 haitians, 6 africans and a pakistanian. The clinical manifestation were: a watery chronical diarrhea in 17 cases a bloody diarrhea in 2 cases; a loss of weight in the 26 cases; a dysphagia in five cases; a jaundice in one patient (due to Kaposi sarcoma of the ampulla of Vater). The digestive lesions found, alone or associated, were necrotizing enteritis (2), ulcerative colitis (1), pseudomembranous colitis (1), candida oesophagitis (10), erythematous duodenitis (6), proctitis (4), Kaposi sarcoma (3) diffuse (2) or localized (1). 13 patients out of the 26 presented opportunistic digestive infections due to one or several germs. The were 10 cases of oesophageal infection (due to (Candida albicans) and 8 cases of enterocolic infection due to Cytomegalovirus (3 cases), Cryptosporidium (3 cases), Mycobacterium avium intracellulare (1 case), Cryptococcus neoformans (1 case). The other digestive infections cases were due to non opportunistic pathogens: Entamoeba histolytica (3 cases); Giardia lamblia (3 cases); Strongyloides stercoralis (2 cases); Salmonella typhi (2 cases); Shigella (1 case). Neither the nature nor the frequency of the digestive infections was different from the first epidemiological group to the second one.

Acquired Immunodeficiency Syndrome↗

Abnormal pancreatic polypeptide release by secretin infusion in Zollinger-Ellison syndrome.

In 28 patients with the Zollinger-Ellison syndrome (ZES), 26 studied before and two after tumor excision, and in 26 age-matched control patients with duodenal ulcer (DU), plasma pancreatic polypeptide and serum gastrin concentrations were studied before, during, and after infusion of pure secretin (3 CU/kg/hr). In 21 ZES patients, gastric acid output was simultaneously studied. Fasting pancreatic polypeptide concentrations were over 300 pmol/liter in five of 26 gastrinomas. In DU, secretin caused a nonsignificant increase in plasma pancreatic polypeptide concentration and markedly decreased gastric acid output. In ZES, however, it resulted in a marked increase of both plasma pancreatic polypeptide concentration and gastric acid output. Basal and post secretin pancreatic polypeptide concentrations showed no correlation with gastric acid output, serum gastrin levels, or the age of the subjects, in DU patients as well as in ZES. These concentrations were not different in ZES patients who had a vagotomy compared to nonvagotomized ZES patients. Furthermore, the pancreatic polypeptide response to intravenous secretin was abolished by gastrinoma excision.

Adult↗