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Biomedical subjects

S Bonfils

Publications and source records attributed to S Bonfils.

At least 55 records · Page 3Linked to original sources

Delayed gastric emptying in anorexia nervosa is improved by completion of a renutrition program.

The effects of renutrition on gastric emptying and upper gastrointestinal symptoms were evaluated in 14 anorexia nervosa patients before and after weight gain. A double-isotope technique was used to measure gastric emptying of both the solid and the liquid phases of the meal. Upper gastrointestinal symptoms were frequent before renutrition, occurring in 78% of the patients. Among these symptoms, nausea, vomiting and gastric fullness were correlated well with slowing in gastric emptying of both solid and liquid phases of the meal, which was demonstrated, respectively, in 10 (71%) and nine (64%) of the 14 patients. For the 11 patients who subsequently gained body weight, we observed, without any pharmacological treatment, an improvement of gastric emptying of both solid and liquid phases of the meal in eight (73%) and seven (64%) patients, respectively. Gastric emptying was unchanged in the three other patients who gained very little weight during the time of the study. As gastric emptying improved, so did nausea, vomiting, and gastric fullness. In three patients who had initially gained weight, nausea and gastric fullness recurred, associated again in all cases with a delay in gastric emptying. In conclusion, in anorexia nervosa, delayed gastric emptying, which is a frequent feature and which is well correlated with some of the upper digestive complaints, can return to normal without any pharmacological treatment. In this improvement, psychological assistance may play a role, together with the correction of the malnutrition.

Adolescent↗

The somatostatin/histaminic pathway balance on gastric secretion could be based on a competitive antagonism.

Measurements of acid and pepsin secretions and of histamine release in response to food alone or in combination with graded doses of antramine (AH), a molecular form of histamine isolated from antral mucosa, with or without somatostatin were performed simultaneously in dogs equipped with a denervated pouch. AH restored somatostatin-inhibited acid and pepsin secretions but with different intensities in regard to the different inhibitory levels induced by somatostatin. AH competitively antagonized somatostatin (1 microgram/kg/h) inhibition of acid secretion, but when stronger levels of inhibition were achieved, AH restored weakly acid secretion. Recovery of pepsin secretion occurred through a competitive mechanism between AH and somatostatin (1 and 2 micrograms/kg/h). There was a close relationship between the secretory outputs and the integrated histamine responses; the slopes of the regression lines might be considered as reflecting the stimulatory activity of blood histamine on secreting cells. For acid secretion, this activity is similar in control and somatostatin (1 microgram/kg/h) tests, while for pepsin secretion it is identical in control and 1 or 2 micrograms/kg/h somatostatin tests. One can speculate that the suppression of the somatostatin inhibitory effects by antramine, within the limits of physiological conditions, results from a competitive mechanism.

Amino Acids↗

Diagnosis and treatment of Zollinger-Ellison syndrome.

A diagnostic and therapeutic strategy for the management of patients with Zollinger-Ellison syndrome has been developed, based on the review of a large personal experience and the most recent literature. The mainstay of a modern ZES management is the eradication of tumoral processes whenever feasible. Diagnosis is centred upon gastric acid and gastrin secretion measurements both in basal conditions and on secretin stimulation. Recognition of other endocrine involvement and familial inheritance is of the utmost importance in distinguishing sporadic ZES patients from those who have the condition known as multiple endocrine neoplasia type I. Blood calcium and phosphorus levels, parathyroid hormone concentration, combined if necessary with urinary cyclic AMP excretion measurement, should be performed routinely once ZES diagnosis is established or highly suspected. Localization of the tumour is the next essential step, and this has been considerably facilitated by the recent development in imaging techniques: it involves computerized axial tomography and selective abdominal angiography, a combination of which allows tumour detection in 60-70% of sporadic gastrinoma patients, with a maximal sensitivity for well-developed hepatic metastases. In sporadic ZES exploratory laparotomy is legitimate when preoperative localization of the tumour has failed; this laparotomy will allow further detection and then eradication of gastrinomas in a significant number of patients. Control of gastric acid secretion is mandatory throughout the work-up period; modern antisecretory agents are efficacious in most cases; total gastrectomy, when control of acid hypersecretion has failed, is now exceptional. Eradication of the tumour should be attempted in cases of sporadic ZES in the absence of recognizable liver involvement. The chance of a definite cure provided by surgery when performed by an experienced surgeon varies from 20% to 60% in pancreatic and ectopic gastrinomas respectively. In ZES patients with MEN I, exploratory laparotomy is seldom indicated (other than for symptomatic associated endocrine secretion), as the chance of a definite cure by surgery is very rare. Parathyroid surgery is often indicated and should take place before any form of abdominal surgery. In cases of hepatic metastases, chemotherapy with streptozocin and fluorouracil is indicated and soon, perhaps, chemo-embolization.

Anti-Ulcer Agents↗

Long-acting somatostatin (SMS 201-995) in the management of Zollinger-Ellison syndrome: evidence for sustained efficacy.

Five patients with Zollinger-Ellison syndrome (ZES) have been treated during 9-12 months with long-acting somatostatin (SMS 201-995). Basal acid output presented a sustained decrease in 4 of 5 cases, below 10 mmol/h in three patients, allowing ranitidine discontinuation. No escape phenomenon was observed. Maximal acid secretion progressively decreased, suggesting an SMS antitrophic effect. Serum gastrin level was affected in a greater extent, showing a mean 87% decrease throughout the treatment period. Thus three patients kept normal serum gastrin levels in the long-term; one escaped to SMS after 9 months. Associated endocrine neoplasia were poorly influenced by SMS. No convincing evidence of tumor size variation was noted. Tolerance of SMS was excellent in the five patients. SMS' antitrophic and antigastrin properties could be of great interest in long-term management of ZES.

Adult↗

Action of somatostatin analogue (SMS 201-995) on the growth-promoting effect resulting from sustained achlorhydria in rat gastric mucosa, with special reference to endocrine cell behaviour.

We investigated whether a new long-acting somatostatin analogue (SMS 201-995) could antagonize the trophic effect induced by hypergastrinaemia, resulting from chronic omeprazole treatment, on the rat gastric mucosa and particularly on endocrine cell growth. SMS was administered concomitantly with omeprazole for 70 days. Gastric morphometric and cell proliferative parameters, gastric acid secretion and plasma gastrin levels were examined. New findings with omeprazole pointed out: (i) a trophic effect on the antral mucosa and (ii) that the increase observed in gastrin cell number was not due to stimulation of gastrin cell production by omeprazole but more likely to a prolongation of the gastrin cells' life span. As compared to omeprazole alone, simultaneous SMS administration significantly decreased the parietal cell (P less than 0.05) and gastrin cell (P less than 0.01) labelling indices, mucosal height of total glandular stomach (P less than 0.05) and antral mucosal height (P less than 0.05). It tended to lower fundic mucosal height and fundic argyrophil cell density (P less than 0.2 and P less than 0.1, respectively). SMS, in our conditions, did not accentuate the inhibitory effect of omeprazole on gastric acid secretion nor reduce high plasma gastrin levels. We conclude that SMS modestly counteracts the growth-promoting effect observed in rat gastric mucosa after prolonged omeprazole treatment.

Achlorhydria↗

Long acting somatostatin treatment of paraneoplastic Cushing's syndrome in a case of Zollinger-Ellison syndrome.

Cushing's syndrome, caused by ectopic ACTH production during Zollinger-Ellison syndrome, raises difficult therapeutic problems. We report a case of clinical and biological efficacy of long acting somatostatin (SMS) in this condition. In a short term study with 200 micrograms SMS bid, symptoms of hypercorticism disappeared while cortisol and ACTH serum concentrations fell below the normal values. Longterm treatment was instituted with 50 micrograms SMS bid. Excellent clinical efficacy as well as normal cortisol and ACTH serum concentrations were maintained during the nine month follow up. Lipotrophic hormone (LPH) serum concentration remained raised. No decrease in size of hepatic metastases was observed. Long acting somatostatin analogues may be useful in endocrine paraneoplastic syndromes.

ACTH Syndrome, Ectopic↗

Gastrin secretion by gastrinoma cells in long-term culture.

Gastrinoma cells from surgical specimens of a primary pancreatic tumor and an hepatic metastasis in two patients with a Zollinger-Ellison syndrome were grown and subcultured for 7 mo. Cultured cells displayed a strong reactivity to heptadecapeptide gastrin antibody and maintained an ultrastructural appearance resembling that of the original tumor cells with the presence of secretory granules of variable size and electron density. Cultured cells also showed the ability to secrete immunoreactive gastrin, and this secretion was further concentration-dependently stimulated by secretin (10(-10)-10(-6) M), carbachol (10(-6) M), and bombesin (10(-10)-10(-6) M). The latter peptide was the more potent stimulant with a maximal effect at 10(-9) M (460 +/- 20% of basal release; P less than 0.05). This stimulation occurred in the absence of extracellular Ca2+ and was potentiated by the addition of dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP; 10(-3) M) into the culture medium. The somatostatin analogue, somatostatin-(201-995), did not alter basal gastrin release but inhibited secretin, carbachol, and bombesin stimulation. Moreover, DBcAMP (10(-3) M) and Ca2+ (1-3 mM) stimulated gastrin release; Ca2+ ionophore A23187 (6 micrograms/ml) enhanced gastrin response to Ca2+ in the early time intervals of incubation. Furthermore the phorbol ester derivative, 12-O-tetradecanoyl phorbol-13-acetate, dramatically stimulated gastrin release (10 times the basal value). We conclude that gastrinoma cells can be cultured over an extended period with maintenance of their capacity to secrete gastrin in response to various hormones and mediators.(ABSTRACT TRUNCATED AT 250 WORDS)

Bombesin↗

Effects of roxatidine acetate on 24-hour gastric acidity. Early evening versus bedtime administration in healthy subjects.

The gastric antisecretory activity of roxatidine acetate was studied on 24-hour intragastric pH in 12 healthy male volunteers. The study was randomised, double-blind and double-dummy where either roxatidine acetate 150 mg as a slow release granulated formulation or placebo were administered at 7.30 pm or 10 pm. Roxatidine acetate 150 mg produced a significant decrease in the number of hours during which gastric acidity ranged between pH 1.5 and 4.0 which was consistent with the pharmacokinetic profile of the drug. There was no significant difference between the median intragastric pH values for early evening and bedtime administration of roxatidine acetate. The present data confirm that roxatidine acetate 150 mg inhibits gastric acid secretion but while a single evening dose is effective in controlling intragastric pH the results suggest there is no clear advantage in an early evening dose compared with a bedtime dose.

Adult↗

Pancreatic polypeptide response to insulin in duodenal ulcer. Different levels in accordance with ulcer activity and its response to treatment.

Pancreatic polypeptide is said to be a marker of vagal tone in duodenal ulcer. To determine whether pancreatic polypeptide levels are related to the course of duodenal ulcer, we studied acid and pancreatic polypeptide responses to insulin in 80 patients with duodenal ulcer disease: 40 with unoperated duodenal ulcer and 40 with proximal vagotomy. Data were analysed in accordance with the presence of an ulcer (active disease) and, when present, in accordance with the ulcer healing on medical treatment (cimetidine, 1 g/day for 4 weeks). In both groups acid and pancreatic polypeptide responses to hypoglycaemia were slightly correlated (r = 0.38) (p less than 0.05). The basal pancreatic polypeptide level was higher in patients with active disease than in those with inactive disease, who had a basal level similar to that of normal subjects of the same age range. Like the insulin-stimulated acid secretion, the pancreatic polypeptide response to insulin hypoglycaemia was higher in patients with active disease than in those with inactive disease (p less than 0.05): 26.1 +/- 3.9 versus 20.1 +/- 4 nmol/l/120 min, respectively, in unoperated patients and 34.8 +/- 2.2 versus 24.3 +/- 2.5 nmol/l/120 min, respectively, after proximal vagotomy. In active disease the pancreatic polypeptide response to insulin hypoglycaemia was higher in subjects whose ulcer did not heal further after cimetidine therapy than in those whose ulcer did. These data suggest that the pancreatic polypeptide response to insulin is an indicator of duodenal ulcer activity and is related to the treatment efficacy. These relationships are partly mediated by increased vagal tone.

Adult↗

Management of Zollinger-Ellison syndrome with gastric antisecretory drugs.

Antisecretory drugs are major tools for management of the Zollinger-Ellison syndrome (ZES). Cimetidine was first used as a successful substitute of total gastrectomy. However with high dosage side effects and an escape from control were observed. As a more potent H2-receptor antagonist ranitidine has obvious advantages and is still largely used. Famotidine is more promising with a longer duration of action and given at lower dosages. Omeprazole could be considered as a treatment of choice with specific action on the proton pump and no side effects. However, with this drug the danger of permanent hypergastrinaemia being associated with fundic carcinoïd induction should be appreciated. Long-acting somatostatin has theoretical advantages in reducing simultaneously acid and gastrin secretion with a potential antitrophic effect. Larger studies are needed to precisely assess the therapeutic potential of the last three drugs.

Antacids↗

Inhibition of food-stimulated acid secretion (intragastric titration) by roxatidine acetate. Dose-response study.

In 10 healthy male volunteers a dose-response study was carried out with roxatidine acetate, 75, 150, 300, and 600 mg, and placebo on food-stimulated gastric acid secretion (intragastric titration (IGT]. The design of the study, with drug intake 150 min before starting IGT, enabled stable inhibition over the 90-min observation period of the test. Cumulative secretory results showed a dose-related acid secretion inhibition (67% for 75 mg; 87.6% for 150 mg; 98.8% for 300 mg; 99.6% for 600 mg). The results were statistically significantly different from placebo and from each other, except for 300 mg versus 600 mg. With a Lineweaver-Burk plot, the ED50 was 41 mg and r = 0.98. Peak concentrations of roxatidine were observed either at T 150 or T 180. Significant correlation (r = 0.7; p less than 0.001) was obtained for the percentage inhibition with 75 mg and 150 mg together versus peak concentrations. Antisecretory potency with the IGT model applied to normal subjects appears to be of the same order for roxatidine acetate and for ranitidine.

Adult↗

Persistence of circadian rhythms in gastric acid, gastrin, and pancreatic polypeptide secretions despite loss of cortisol and body temperature rhythms in man under stress.

During organic stress, severe dysfunctions of fundamental biological phenomena, such as modification of vagal tone, have been described. These dysfunctions could induce changes in the rhythm of acid secretion and/or its hormonal control. We therefore analyzed the effects of acute respiratory failure on the 24 h variations in intragastric pH, serum gastrin, and pancreatic polypeptide levels, taken as a marker of vagal tone. Body temperature and plasma cortisol circadian rhythms were used as marker rhythms. Twelve patients with chronic obstructive pulmonary disease complicated with acute respiratory failure were studied before and during continuous enteral nutrition; half of the patients received ranitidine, a H2 blocker. During the 3 days of the study, intragastric pH was below 2.5 for only one third of the time. No difference was observed between the placebo and the ranitidine groups. Plasma pancreatic polypeptide was within normal ranges despite increased cortisol levels. Gastrin levels reflected changes in intragastric pH over the 24 h time frame and were noted to increase during ranitidine and enteral nutrition. Despite the loss of cortisol and body temperature circadian rhythmicity all throughout the study, circadian rhythms were maintained or restored during the different therapeutic regimens for intragastric pH, serum gastrin, and pancreatic polypeptide levels. Moreover, an ultradian rhythm for gastrin before any treatment, a circadian rhythm for intragastric pH on enteral nutrition, a circadian rhythm for intragastric pH, plasma gastrin and plasma pancreatic polypeptide on ranitidine regimen were observed. Thus during acute respiratory failure, certain physiological circadian rhythms persisted despite the disappearance of "marker" rhythms. Furthermore, these rhythms for digestive secretions could be pharmacologically restored.

Acute Disease↗

[The effect of ranitidine on gastric pH measured by continuous monitoring over 24 hours in healthy subjects. Comparison of 2 methods of administration: 150 mg morning and night, vs 300 mg in a single dose at night].

The gastric pH of 8 healthy subjects was determined, in a continuous fashion, during three different 24 hour periods corresponding to the 3 following treatments: Placebo, ranitidine 150 mg twice per day, and ranitidine 300 mg in the evening. During each period, the feeding conditions were normal and standardized. The results are expressed in terms of the number of hours under a threshold pH value. In comparison with the placebo, ranitidine, regardless of its mode of administration, results in a significant decrease of the mean number of hours under pH 1.5, 2 and 3 during 24 hours; no significant difference was demonstrated between the two modes of administration in 24 hours. During the 12 night-hours, a single dose of 300 mg of ranitidine was more effective to ranitidine taken in 2 doses for pH thresholds of 2 and 3, while during the 12 day-hours, no difference was demonstrated for pH thresholds of 1.5, 2 and 3. The analysis of the mean pH graphs in relation to time, suggests that a single 300 mg dose is more effective than the same dose divided into 2 doses during the day. These results tally with the variations of ranitidine plasma levels in 24 hours. These results justify, from a pharmacological standpoint, the prescription of a single dose of ranitidine, in the evening.

Adult↗

Development of gastric argyrophil carcinoid tumors in a case of Zollinger-Ellison syndrome with primary hyperparathyroidism during long-term antisecretory treatment.

Fundic argyrophil carcinoid tumors developed in the course of a 5-year continuous treatment with high dosages of H2-antagonists in a well-documented case of Zollinger-Ellison syndrome with primary hyperparathyroidism, high basal acid output, and serum gastrin. Approximately 100 small polyps were disseminated throughout the gastric fundus exclusively, leading to total gastrectomy. Metastatic carcinoid in a lymph node and pancreatic gastrinomas also were found at surgery. Gastric endocrine cell proliferation varied from simple argyrophil cell hyperplasia to carcinoid tumors eroding the surface and infiltrating the submucosa. Ultrastructural studies showed that the tumoral proliferation was heterogeneous, and included tumors composed of enterochromaffin (EC) and typical enterochromaffin-like (EC-L) cells, and tumors in which a majority of cells exhibited dense round granules resembling those of A-like or D1/P endocrine cell types. The risk of developing gastric fundic carcinoid tumors in ZES patients submitted to long-term antisecretory treatment should be given increased attention.

Carcinoid Tumor↗

Small bowel and plasma gastrin rhythms in cats.

The purpose of this experiment was to study the possible role of the gastric antrum and small bowel in the rhythm(s) of plasma gastrin. The cat was used as the laboratory animal. Three groups of cats were provided with a gastric fistula for the study of gastric acid and plasma gastrin rhythms. The first group (N = 7) served as controls. A second group (N = 3) was antrectomized and later subjected to a 80% small bowel resection. Gastric acid secretions were collected every 30 min from 0800 to 2400. Blood samples for determination of gastrin were drawn every 2 hr from 0800 to 2400. In control animals a circadian (i.e. approximately 24 hr) and 3 ultradian (i.e. less than 24 hr) rhythms were detected for acid output. In the antrectomized cats, circadian and ultradian rhythms were documented. After small bowel resection circadian and ultradian rhythms in gastric acid secretion were observed. For plasma gastrin, circadian and ultradian rhythms were found in the control cats. In the antrectomized cats no rhythms were observed. After small bowel resection an ultradian rhythm reappeared in these antrectomized cats. Removal of the antrum in the cat induces disappearance of circadian and ultradian rhythms of plasma gastrin but fails to modify the acid rhythms. Small bowel resection results in the reappearance of an ultradian rhythm for plasma gastrin and a shift in acrophase for the circadian rhythm in acid secretion.

Activity Cycles↗