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Biomedical subjects

M Mignon

Publications and source records attributed to M Mignon.

At least 109 records · Page 6Linked to original sources

[Variations of plasma gastrin (basal and postprandial) in ththtreatmentof duodenal ulcer with either enprostil or ranitidine. Correlations with rates of relapse].

Enprostil, a synthetic E2-prostaglandin efficacious for duodenal ulcer healing, presents both antisecretory and antigastrinic effects. This is at variance with the elevation of plasma gastrin observed with ranitidine. OBJECTIVE--This leads us to compare enprostil and ranitidine on the following points: a) variations of plasma gastrin (basal and postprandial) parameters over a 6-week conventional treatment; b) correlation studies between ulcer relapses (frequency and temporal evolution) after treatment discontinuation and various gastrinic criteria. METHODS--Among a group of 642 patients followed for ulcer relapse, 165 were considered for gastrin (78 of the "Enprostil" group and 87 of the "Ranitidine" group). RESULTS--Initially, both populations were comparable for clinical and plasma gastrin parameters. After 6 weeks of treatment, the increases in the various gastrin parameters (basal, postprandial, peak, integraded) were significantly greater and the absolute values higher (Wilcoxon, P < 0.001) with ranitidine than with enprostil. No correlation was found between relapse occurrence after drug discontinuation and these gastrin parameters. CONCLUSIONS--Ranitidine hypergastrinemia seems directly related to gastric hyposecretion whereas its absence with enprostil is likely more dependent upon a specific antigastrinic activity than on a reduced antisecretory activity. Those differences in mechanism of action have no consequence on the stability of ulcer obtained by either drug.

Adolescent↗

[Comparative efficacy of lansoprazole and omeprazole on the intragastric pH measured over a period of 24 hours and on the basal].

OBJECTIVES: This paper aimed at evaluating the comparative efficacy of lansoprazole and omeprazole in reducing gastric acid secretion in patients suffering from Zollinger-Ellison syndrome. METHODS: Nine patients with non-resected gastrinoma(s) an previously well controlled by omeprazole (mean dosage 75 +/- 12.4 (SEM) mg/day; extremes: 20-160 mg/day) underwent 24-hour intragastric pH-metry, baseline acid output before next dosing and serum gastrin dosages, receiving their usual therapy and thereafter lansoprazole at a weight equivalent posology (mean dosage 81.6 +/- 12.5 (SEM) mg/day; extremes: 30-165 mg/day). RESULTS: Lansoprazole maintained intragastric pH and basal acid output at therapeutic levels, but a discrete reacidification, that deserves confirmation on a larger group of patients, was observed between the meals. CONCLUSIONS: The possible long-term benefit of this phenomenon, especially on gastrinemia and the fundic ECL-cells density and gastric bacterial content, remains to be evaluated.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Antacid activity of calcium carbonate and hydrotalcite tablets. Comparison between in vitro evaluation using the "artificial stomach-duodenum" model and in vivo pH-metry in healthy volunteers.

Antacid activity of calcium carbonate (CAM, Rennie) and of hydrotalcite (HYD) containing tablets has been assessed in vitro using computer-controlled "artificial stomach-duodenum" model, including or not a piece of hog gastric mucosa in the gastric reservoir, and simulating the constant flux system or the normal gastroduodenal flux regulation. The data obtained under the latter condition were compared to those obtained in vivo by pH-metry in 12 healthy volunteers, in response to one administration of 2 tablets. The theoretical maximal capacity was similar when 1 tablet of CAM or of HYD was added to the gastric contents, including or not a piece of gastric mucosa, close to 95 H+ mmol. The reduction of acid load penetrating into the duodenum and the duodenal pH were of the same magnitude in response to both antacids. When normal gastroduodenal flux regulation was simulated, a dose-response curve, constructed by 1, 2 or 3 tablets, resulted in the same antacid characteristics in response to both antacids. The maximal gastric and the mean duodenal pH values obtained with CAM were, however, higher than with HYD, corresponding to a greater neutralizing activity developed by CAM than by HYD. The comparison between in vivo administration of two tablets of each antacid and the in vitro model simulating normal gastroduodenal flux regulation in response to the addition of two tablets resulted in similar data. The maximal pH values obtained in in vivo assays were slightly lower than in vitro, depending on the ratio of antacid amount to gastric acid content, well established in in vitro conditions and unknown in in vivo situations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Dose-response effect of lansoprazole in patients with Zollinger-Ellison syndrome].

Lansoprazole, a new substituted benzimidazole, is an effective acid proton pump inhibitor acting by inhibiting selectively H+/K+ ATPase of the gastric parietal cell. This study was performed to assess the effect of successive 30, 60, 90 and 120 mg dosages of lansoprazole in 4 patients suffering from Zollinger-Ellison syndrome. The basal gastric acid output was markedly inhibited in comparison with baseline values (mean maximal reduction: 87%; extremes: 75-99%) and was dose-related. Lansoprazole inhibited pepsin output globally with a dose range effect between 30 and 90 mg/day. The treatment induced a rapid relief of clinical symptoms. No biological abnormality was noted. These data proved that lansoprazole is efficient for treating gastric acid hypersecretion in patients suffering from ZES.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Use of superfused rat skeletal muscle for metabolic studies: assessment of pH by 31P n.m.r.

We developed a muscle superfusion system suitable for metabolic studies of small isolated rat muscle ex vivo in real time and in a non-destructive manner by n.m.r. spectroscopy. In order to determine biochemical stability of superfused extensor digitorum longus (EDL) muscle (from fasted 45 and 100 g rats), the energy state and the pH of muscle were continuously monitored by 31P n.m.r. spectroscopy. ATP and phosphocreatine remained stable during 2 h whatever the muscle size (20 or 45 mg). Neither metabolite was a sensitive probe of possible metabolic compartmentation within muscle under our experimental conditions. By contrast, the chemical shift of Pi by its sensitivity to pH was a discriminant factor in the assessment of muscle stability. Indeed, heterogeneity of pH was observed only in the 45 mg EDL muscle resulting from a core region with loss of glycogen. Together, these observations suggest deviations of energy metabolism to supply ATP. Consequently, pH may be considered as a new real-time criterion for monitoring a metabolic heterogeneity due to changes in energy metabolism of muscle preparations ex vivo.

Adenosine Triphosphate↗

Hepatic arterial chemoembolization in patients with liver metastases of endocrine tumors. A prospective phase II study in 24 patients.

BACKGROUND: Liver metastases of endocrine tumors are of major prognostic significance. The various therapeutic approaches have given disappointing results; however, locoregional treatment has allowed transient control of hepatic tumor growth. METHODS: Twenty-four patients with liver metastases of endocrine tumors (mainly carcinoid tumors [n = 18] and gastrinomas [n = 5]) were included in a Phase II study of hepatic arterial chemoembolization (CE). Metastases were bilateral in all patients and invaded more than 50% of the liver in 12. They were synchronous of the primary tumor in 62.5% of the patients. Seventeen patients had not responded to previous intravenous chemotherapy. CE courses were performed every 3 months using an emulsion of 10 ml of iodized oil and doxorubicin 50 mg/m2 injected into tumor vessels, followed by CE arterial occlusion with gelatin sponge particles. Seventy-one CE courses were performed in 23 patients; there was one technical failure. RESULTS: Among patients with carcinoid tumors, disappearance of diarrhea and/or flushing was observed in 8 of 11. Serotonin and/or its metabolite 5-hydroxyindoleacetic acid levels decreased by more than 50% in 57% of the patients. The size of liver metastases decreased by at least 50% in 6 of 18 patients, i.e., in 33% (range, 12-54%). Two had complete responses. The median duration of the responses was 14 months (range, 6-40). Among patients with noncarcinoid tumors, minor response or stabilization occurred in three of five patients. Major side effects were bleeding peptic ulcer (one patient) and oligoanuric renal failure (one patient). Abdominal pain, fever, and increases in hepatic enzyme levels were common and transient. CONCLUSIONS: These results suggest that CE is effective in patients with liver metastases of endocrine tumors, mainly in carcinoids. In the latter, CE allows control of the carcinoid syndrome and regression or stabilization of the liver tumors in 80% of patients.

Adult↗

Gastric endocrine cell evolution in patients with Zollinger-Ellison syndrome. Influence of gastrinoma growth and long-term omeprazole treatment.

Evolution of gastrinoma tumoral mass, fasting serum gastrin concentrations, and gastric endocrine cells has been analyzed in 21 patients with the Zollinger-Ellison syndrome committed to long-term omeprazole treatment (up to 7.75 years, median 37 months). Gastrinoma growth was seen in eight patients. Significant increase in serum gastrin was only observed in the group of patients with gastrinoma growth. Fundic argyrophil cell densities were correlated with serum gastrin (r' = 0.68, P = 0.002). Argyrophil and antral gastrin cell densities significantly increased during the survey, but increases were greater in the group with gastrinoma growth (respectively, +136% and +131%) than in the other group (respectively, +34% and +43%). Progression in the degree of argyrophil cell hyperplasia, noted qualitatively, was observed in 11 patients. Fundic carcinoids developed in three of these 11 patients, all three having multiple endocrine neoplasia type 1 (MEN 1). Positive linear individual correlations (r > or = 0.85) between argyrophil cell densities and corresponding durations of omeprazole treatment were found in nine of the 10 patients studied at least three times and who had a clear-cut increase in those cell densities. Thus, increase in serum gastrin and fundic argyrophil cell densities appeared closely associated with gastrinoma growth; however, duration of drug-induced hypochlorhydria may also affect cell proliferation.

APUD Cells↗

A case of scurvy presenting with cutaneous and articular signs.

This report is on a patient, who presented purpura and hemarthrosis in a context of vitamin C deficiency. This case gives us the opportunity to discuss the differential diagnosis, the clinical features, the pathogenicity and the treatment of this rare condition.

Ascorbic Acid↗

Chronic endogenous hypergastrinemia in humans: evidence for a mitogenic effect on the colonic mucosa.

BACKGROUND: Information concerning the influence that gastrin may exert on the colon is fragmentary and somewhat controversial. This study analyzed the effect of chronic endogenous hypergastrinemia on cell proliferation and tumor occurrence in the human colonic mucosa. METHODS: Twenty-three consecutive hypergastrinemic patients presenting with the Zollinger-Ellison syndrome and 18 normogastrinemic subjects were studied. All had fasting serum gastrin determination, colonoscopy, and cell kinetic measurement in two colonic sites using in vitro 5'-bromodeoxyuridine incorporation. RESULTS: Macroscopic tumors, one endocrine and five adenomas, were found in 5 of 23 hypergastrinemic patients, without apparent relationship with the level of gastrin. The labeling indices were significantly higher in hypergastrinemic than in normogastrinemic individuals in the right and left colon, (P < 0.002 to P < 0.001) without resulting in colonic cell hyperplasia. There was no correlation between labeling indices and serum gastrin concentrations or duration of hypergastrinemia. The DNA labeling distribution along the crypt was normal in the two groups, without expansion of the proliferative zone towards the surface. CONCLUSIONS: These results showed for the first time that long-lasting endogenous hypergastrinemia is accompanied by increased in vivo cell proliferation in the human colonic mucosa. However, the prevalence of adenomas (17.4%) in patients, all more than 50 years old, may not be different from that in the general population.

Adenoma↗

Is the multiple endocrine neoplasia type 1 gene a suppressor for fundic argyrophil tumors in the Zollinger-Ellison syndrome?

In the Zollinger-Ellison syndrome, fundic argyrophil carcinoid tumors have been described only in the small genetically defined subgroup of patients who have the multiple endocrine neoplasia type 1 syndrome (MEN-1). Allelic losses on 11q13, on which MEN-1 gene has been localized, have been noted in parathyroid and pancreatic tumors of patients with MEN-1, suggesting that the MEN-1 gene could act as a recessive tumor suppressor gene. One fundic argyrophil carcinoid tumor from a patient with the Zollinger-Ellison syndrome and MEN-1 was studied. Loss of heterozygosity in the tumor DNA at loci close to MEN-1 locus was looked for using Southern technique with six DNA probes. Segregation of alleles was examined in relatives. In the tumor DNA, we found the loss of one allele with PYGM, the closest probe to the MEN-1 locus. The allele lost in the tumor had been transmitted by the unaffected parent. This suggests that in patients with the Zollinger-Ellison syndrome and MEN-1, the promotion of fundic argyrophil carcinoid tumors results from the inactivation of the two copies of MEN-1 gene and that fundic argyrophil carcinoid tumors may be included in the spectrum of MEN-1-related tumors.

Adult↗

Transferrin-binding proteins isolated from Neisseria meningitidis elicit protective and bactericidal antibodies in laboratory animals.

Transferrin-binding proteins (Tbps) were affinity-isolated from group B Neisseria meningitidis strain B16B6 and used to raise specific antisera. Administration of the antisera to mice loaded with human transferrin before bacterial challenge significantly protected the animals from death. In active immunization studies, mice received three 25 micrograms injections of purified Tbps over a period of 28 days, 7 days after which they were challenged with N. meningitidis. The survival rate in immunized mice was much higher than in control groups. In both active and passive immunization experiments mice were protected against at least 100 LD50. A specific Tbp antiserum was highly bactericidal against the parent strain and against approximately half of the strains tested.

Animals↗

Clinical, anatomical, and evolutive features of patients with the Zollinger-Ellison syndrome combined with type I multiple endocrine neoplasia.

The clinical evolution of type I multiple endocrine neoplasia (MEN I) was studied in 45 patients among a consecutive series of 172 with Zollinger-Ellison syndrome (ZES). These 172 patients were seen in our hospital between 1959 and 1989. Diarrhea was half as frequent in ZES-MEN I as in sporadic ZES cases. At diagnosis, mean basal acid output and serum gastrin levels in MEN I patients (28.8 +/- 6.6 mmol/h and 587 +/- 487 pg/ml, respectively) were not different from those observed in the others with sporadic ZES. Laparotomy was performed in all 36 patients with no diffuse liver involvement to attempt the removal of gastrinomas. Twenty-nine patients had adenomas, located in the pancreas in 21, in the duodenal wall in 3, and in both in 5. Adenomas were multiple in 23 cases (78%). No tumor was found in seven patients. Twenty-nine of the 36 operated patients were tumor-free after surgery; 7 died in the postoperative period between 1959 and 1970. Median follow-up of the 38 other patients was 95 months (range 17-278 months). Among the 24 patients without residual tumor at discharge (group I), biological and/or morphological evidence of a persistent or recurrent source of gastrin was obtained in 22. Among the 14 patients with residual tumor (group II), an increase in tumor size was seen in 5 after a median of 27 months (range 9-36 months), while no change occurred in 9 after 54 months (3-100 months). Actuarial survival curves were not different, either in group I versus group II patients (67 and 72% at 5-year follow-up, respectively) or in MEN I versus sporadic ZES patients. Apparently, complete resection of primary tumor did not reduce the incidence of subsequent liver metastases. In all, 21 of the 45 patients had malignant gastrinomas (47%), consisting of liver metastases in 14 (31%), metastatic lymph nodes in 11 (24%), and lung metastases in 2 (4%). Monitoring of fundic argyrophil cells disclosed hyperplasia in 13 of the 14 MEN I patients (92%), and 5 had invasive carcinoid tumors. Taken together, these results prompt us to recommend that in ZES-MEN I patients, surgery should be avoided and oxyntic mucosa regularly monitored.

Adolescent↗

Acute treatment of duodenal ulcer: experience with lansoprazole.

Clinical experience with lansoprazole in the acute treatment of duodenal ulcer patients has been compared with treatment using placebo, H2-antagonists or omeprazole. Among the various lansoprazole dosage regimens that have been tested, 30 mg daily for 4 weeks appears to be the optimal regimen to relieve pain rapidly and to heal ulceration in up to 90-95% of patients. Lansoprazole tolerability in the short term appears excellent, most adverse effects are trivial and not dose related. Duodenal ulcer relapse after ulcer healing with lansoprazole appears to occur at a rate similar to that observed after treatment with omeprazole or histamine H2-antagonists.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Long-term treatment with octreotide in patients with the Zollinger-Ellison syndrome.

This study reports the effects of 4 and 5-year treatment with octreotide (200 micrograms sc bid) in the Zollinger-Ellison syndrome (ZES). No symptoms related to acid hypersecretion were observed in the four patients throughout the study, and upper GI endoscopy was normal. Basal acid output (BAO) measured 12 h after injection, was below 10 mmol h-1 in three to four patients and previous ranitidine treatment was discontinued. In the fourth case (pretreatment BAO value: 115 mmol h-1), BAO progressively decreased to 42 mmol h-1 after 5 years of octreotide treatment. At the end of the study, serum gastrin levels were 58.5% (30-68) of the pretreatment values and two patients had normal gastrin levels. Peak acid output (PAO) decreased markedly after 2, 4 and 5 years, by 68% (35-89) suggesting that octreotide had exerted an antitrophic effect on parietal cell mass. Diffuse hyperplasia of fundic argyrophil cells present in two patients before octreotide, decreased during the treatment. Mean argyrophil cell density for all patients was not significantly modified. Antral gastrin-cell density was in the normal range. No long-term side effect of octreotide treatment was observed. Although octreotide may not be considered as a substitute for benzimidazoles in the treatment of ZES, its specific properties may be of therapeutic benefit in some ZES patients.

Adult↗

Two year maintenance treatment of duodenal ulcer disease with ranitidine 150 mg: a prospective multicentre randomised study. GEMUD (Groupe d'Etude de la Maladie Ulcéreuse Duodénale).

Maintenance treatment of duodenal ulcer (DU) with ranitidine 150 mg/day was compared with placebo in a two year prospective multicentre randomised study. Three hundred and ninety nine patients were included (mean age: 44.7 years, M/F ratio = 2.47/1; 37.6% of smokers) in placebo (n = 202) and ranitidine (n = 197) groups. Efficacy was assessed by the length of time to the first ulcer pain attack (with or without endoscopic confirmation) or DU complication. One hundred and fourteen patients of 399 (28.6%) had incomplete follow up. Actuarial survival curves of patients without ulcer pain (26 and 53% at two years in placebo and ranitidine groups, respectively) were significantly different (p < 0.0001). Endoscopies were performed depending on physicians' decision (mainly where there was severe pain or complication). Patients without relapses from endoscopy were more frequent in the ranitidine group (83%) than in the placebo group (47%, p < 0.0001). A greater incidence of complications, mainly bleeding, was also seen in the placebo group (13 complications v two in the ranitidine group, p < 0.002). No factor predicting DU relapse was identified. No important side effect was encountered. Ranitidine 150 mg/day is effective and well tolerated in preventing ulcer pain attacks and DU complications for up to two years.

Adult↗