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Biomedical subjects

M Mignon

Publications and source records attributed to M Mignon.

At least 127 records · Page 7Linked to original sources

Gastric secretion of platelet activating factor and precursors in healthy humans: effect of pentagastrin.

The release of platelet activating factor (PAF-ACETHER or PAF) and its precursors in the gastric lumen was assessed in 13 normal subjects in basal condition and after stimulation by gastrin. Acid, pepsin, and sialic acid outputs were determined under the same conditions. Gastric juice was collected using a nasogastric tube after overnight fast in basal condition for 60 minutes, then under pentagastrin infusion (6 micrograms/kg/hr for 60 minutes). Platelet activating factor was detected at low concentration in 4/13 subjects under basal condition (mean (SEM) 1.2 (0.6) pg/hr) while high concentrations of lyso platelet activating factor (6.1 (1.8) microgram/hr) and of alkyl-acyl-glycerophosphocholine (AAGPC) (11.5 (3) micrograms/hr) were found in 13 and 11 subjects, respectively. Platelet activating factor was not detected during pentagastrin infusion, while lyso platelet activating factor and alkyl-acyl-glycerophosphocholine were detected in 13 and in 12 subjects, respectively. Compared with the basal condition these platelet activating factor precursors increased significantly (p < 0.001) going up to fivefold baseline (31.8 (6.8) micrograms/hr and 53 (9.3) micrograms/hr respectively) in response to pentagastrin. There was a positive correlation between platelet activating factor precursors and acid or pepsin output but not between platelet activating factor precursors and sialic acid. As sialic acid may be considered an index of mucus glycoprotein degradation, it seems that gastrin stimulation of gastric epithelial cells results in a concomittant secretion of platelet activating factor precursors, acid, and pepsin irrespective of mucus glycoprotein degradation.

Acetylation↗

Gastric endocrine cell proliferation and fundic argyrophil carcinoid tumors in patients with the Zollinger-Ellison syndrome.

The Zollinger-Ellison syndrome (ZES) is characterized by hyperchlorhydria due to sustained hypergastrinemia of tumoral origin. In ZES, as in all pathological and experimental conditions associated with chronic hypergastrinemia, endocrine argyrophil cells, particularly enterochromaffin-like cells, proliferate in the fundic mucosa. In patients with ZES, fundic argyrophil carcinoids only develop in those patients who also have multiple endocrine neoplasia type 1. The authors review factors which might influence fundic argyrophil cell proliferation in the ZES. Clinical characteristics of the patients with fundic argyrophil carcinoid tumors as well as pathology and the putative mechanisms of development of these tumors are described.

Animals↗

Chromogranin A and pancreastatin-like immunoreactivity in serum of gastrinoma patients.

Gastrin and pancreastatin-like immunoreactivity were determined by radioimmunoassay methods and chromogranin A was determined by enzyme-linked immunoassay in sera from 18 patients with gastrinomas (Zollinger-Ellison syndrome) and in 20 age and sex matched controls. Gastrin serum levels in the gastrinoma patients were in the range 26-80,000 pmol/l, and in the controls 5-31 pmol/l. Chromogranin A serum levels in the gastrinoma group were in the range 6-2,700 ng/ml (mean +/- SEM: 400 +/- 147 ng/ml). The mean value of chromogranin A was significantly higher than in the control group (8 +/- 2 ng/ml, p = 0.008). The serum levels of pancreastatin-like immunoreactivity in the gastrinoma patients were in the range 23-1,994 pg/ml (597 +/- 123 pg/ml). The mean value of pancreastatin-like immunoreactivity in the gastrinoma group was significantly higher than in the control group (104 +/- 25 pg/ml, p = 0.0002). The levels of chromogranin A and pancreastatin-like immunoreactivity were significantly higher in patients with verified metastatic disease (p = 0.04, p = 0.01 respectively). There was a significantly positive correlation between levels of gastrin and pancreastatin-like immunoreactivity (r = 0.7, p = 0.002), while no correlation was found between gastrin and chromogranin A levels or between levels of chromogranin A and pancreastatin-like immunoreactivity. The study demonstrates an elevation of both chromogranin A and pancreastatin-like immunoreactivity in serum of gastrinoma patients. The lack of correlation between gastrin and chromogranin A, however, gives an indication that the gastrinoma cells are not the main source of serum chromogranin A elevation.

Adult↗

[Increase of resting energy expenditure during flare-ups in Crohn disease].

Crohn's disease is an inflammatory process commonly characterized by phases of flare-up. Weight loss and malnutrition are prominent features in the course of the disease, especially during acute episodes. It is therefore important to define energy needs. Curiously, resting energy expenditure (REE) has rarely been studied in Crohn's disease, and never in relation with the activity of the disease. We therefore determined REE together with body composition (fat free mass, FFM), Crohn's disease activity index (CDAI) and plasma acute phase proteins in 70 patients: during flare-up in 41 and during clinical remission (CDAI < 150) in 29. We found an increase in REE in patients with active disease (CDAI > 150), as compared with patients in remission, when REE was expressed as a function of FFM: 31.7 +/- 2.7 versus 29.4 +/- 3.3 kcal/kg FFM/day (P < 0.01). The mean REE/FFM was 8% higher during flare-up than during remission, and was correlated to both clinical (CDAI; P = 0.011) and biological inflammatory activity indices (C reactive protein, P = 0.018; orosomucoid, P = 0.024). In some patients, the REE was in the normal range, despite an increase in REE/FFM, because of a decrease in FFM due to hypermetabolism. In 8 patients treated successfully by total parenteral nutrition for a massive flare-up, REE/FFM was increased before TPN (36.6 +/- 3.0 kcal/kg/day), and decreased after 4 weeks of TPN (31.4 +/- 1.8 kcal/kg/day; P < 0.001), returning within normal values in 7 patients.

Adult↗

[Ileo-anal "pouchitis": a still misunderstood pathology].

Chronic and/or acute inflammation of the ileal reservoir, so-called "pouchitis", is a frequently observed long-term complication of the ileo-anal "pouch" anastomosis. In ulcerative colitis patients, the prevalence of "pouchitis" varies from less than 10% to higher than 40%. These large variations reflect differences in diagnostic criteria and length of follow-up. The definition of "pouchitis" should include clinical symptoms, macroscopic inflammatory lesions at endoscopy and histological evidence of intense acute inflammation of the reservoir mucosa. Local bacterial overgrowth, lack of short chain fatty acids, increased secondary biliary acids, decreased intraepithelial T-lymphocytes and oxygen derived free-radicals could be implicated in the pathogenesis of pouchitis. In the absence of definite aetiology for pouchitis, its treatment is purely empirical: metronidazole, corticosteroids and 5-aminosalicylic acids are the most used drugs. The long-term consequences of the partial colic metaplasia of the pouch mucosa remain to be elucidated by regular clinical, endoscopical and histological longitudinal.

Adrenal Cortex Hormones↗

Treatment of patients with Zollinger-Ellison syndrome.

In the treatment of Zollinger-Ellison syndrome patients with severe disease and acid hypersecretion, proton pump inhibitors are the drugs of choice. Data have now been accumulated on lansoprazole treatment of 41 patients (21 treated at the National Institutes of Health [NIH], Bethesda, Maryland, USA, and 20 treated at the Bichat-Claude Bernard Hospital, Paris, France). Short-term studies of the inhibitory action of lansoprazole on acid secretion have been carried out in both institutions. Our group first performed a dose-response analysis of the efficacy of lansoprazole in reducing basal acid output (BAO) in four patients with severe Zollinger-Ellison syndrome (mean BAO 52 +/- 9 [SD] mmol H+/h) who had previously been treated with a mean omeprazole dosage of 75 mg/day. The maximum acid inhibitory effect was obtained with lansoprazole 60-90 mg/day. The 40-hour duration of action of lansoprazole appears equivalent to that of omeprazole. In a second study at the Bichat-Claude Bernard Hospital, nine Zollinger-Ellison syndrome patients underwent 24-hour intragastric pH monitoring while receiving lansoprazole (mean dosage 80 mg/day, range 30-165 mg/day) or omeprazole (mean dosage 75 mg/day, range 20-180 mg/day). The acid inhibitory activity of the two drugs was comparable. Those patients are currently receiving long-term maintenance treatment with lansoprazole, and satisfactory clinical and biological secretory control has been achieved. The long-term safety and efficacy of lansoprazole administration were studied in the 21 patients followed at the NIH. In those patients the initial maintenance dose was determined using acid inhibition studies; in all patients lansoprazole controlled gastric acid hypersecretion and peptic symptoms in both the short and long term. The mean initial maintenance dose was 60 mg QID, except for two patients who required 60 mg BID. During long-term treatment (mean duration 31 months, range 1-43 months), six patients required a dosage increase within the first year, while the lansoprazole dose could be reduced in six others. The safety profile of lansoprazole has been excellent. Comparable results have been noted in nine Zollinger-Ellison syndrome patients during an ongoing evaluation in our institution. These studies indicate that lansoprazole is an efficacious, well-tolerated antisecretory agent in patients with Zollinger-Ellison syndrome.

2-Pyridinylmethylsulfinylbenzimidazoles↗

[Is ileorectal anastomosis still a valid therapeutic alternative in the surgical treatment of hemorrhagic rectocolitis? Analysis of the functional, endoscopic and histologic result of 74 cases].

The objectives of this study were to determine the functional results of ileorectal anastomosis (IRA) and the endoscopical and histological outcome of the rectal stump in 74 patients operated on for ulcerative colitis. Median follow-up was 7.5 years (range 1 to 35). Functional results, as defined by the usual accepted criteria, were good in 80% of patients. The mean daily number of bowel movements was 4.2 +/- 1.6 (SD). Long term endoscopical and histological features improved in most of cases and only 13.3% of rectal biopsies showed the persistence of acute inflammatory changes; 28.4% of the patients had one or more episodes of acute proctitis during the follow-up period, but none of the patients required proctectomy. One case of severe dysplasia was disclosed, leading to proctectomy. A second case of proctectomy was performed in a patient with microrectum. Biopsies performed preoperatively in this case showed the only case of moderate dysplasia found in our population. Provided that the usual contraindications to this surgical procedure are observed, IRA is still a valid option in the surgical treatment of ulcerative colitis.

Adolescent↗

Current status of liver transplantation (LT) in France and specificities of French ethical attitudes concerning LT.

The authors report first on the current status of liver transplantation in France and underline its exponential development. The main indications for this procedure are outlined for adults as well as for children. The modalities of distribution of livers harvested by strictly controlled university teams are also briefly described. The specificities of French ethical attitudes towards liver transplantation are discussed. They concern the donor, the recipient and the society. Legal dispositions stipulating the presumed consent of the donor and accrediting the notion of "cerebral death" have eased the development of liver transplantation in France. Despite these measures shortage in liver available for grafts results in still too large waiting list and fosters nation-wide campaign to encourage organ donation. There is, in France, a strong consensus for a strict sticking to the absolute principles of gratuity of organ donation and non-marketing of excised organs available for graft. As stated recently by Thomas Starzl, liver transplantation has become the second most commonly performed solid organ transplant after kidney transplant. In the latin Europe, the idea of organ transplantation is in the mind of people for a long time as illustrated from paintings or carvings that can still be seen in several roman catholic churches of the Middle Age. Although, liver transplantation in man developed only after the pioneer work of Thomas Starzl in Pittsburg, it is fair to recall that Alexis Carrel (1908, Noble Prize), from France, opened the way to organ transplantation by performing in animals the first vascular sutures and organ auto- or homografts.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Significance and regulation of gastric secretion of platelet-activating factor (PAF-acether) in man.

Platelet-activating factor (PAF) has been implicated in the pathogenesis of acute inflammatory and ulcerative diseases of the upper gastrointestinal tract. In the present study, we compared the gastric output of PAF and its precursors with gastric acid output, in patients with various upper gastrointestinal tract diseases and healthy controls. PAF and precursors were also extracted from gastric biopsies from subjects with chronic gastritis and/or gastric colonization by Helicobacter pylori. Under basal conditions, hourly gastric PAF output increased in esophagitis and erosive gastritis, but not in duodenal ulcer or Zollinger-Ellison syndrome. In the gastric juice of duodenal ulcer patients, PAF output rose after secretin, but in patients with Zollinger-Ellison syndrome, PAF was only detected when gastric acid secretion had been reduced by antisecretory drugs and no concurrent changes were observed in serum gastrin levels. After pentagastrin, patients and controls exhibited a significant decrease in PAF output and a negative correlation was found between PAF and acid outputs (r = -0.57, p < 0.01). When PAF was incubated with gastric juice in vitro, it underwent degradation irrespective of the medium pH. We found no relation between the outputs of PAF and precursors and the severity of gastritis or gastric colonization by H. pylori. Overall, these results suggest that PAF might be released in the stomach by gastric epithelial cells and could be responsible for mucosal injury of the upper gastrointestinal tract.

Adult↗

An artificial stomach-duodenum model for the in-vitro evaluation of antacids.

To improve the dynamic in-vitro evaluation of the effects of antacids, we have developed the 'artificial stomach' model by adding a 'duodenal reservoir' to receive the gastric emptying flux and simulated bicarbonate secretion, thus constituting an 'artificial stomach-duodenum' model. With this model we measured antacid-induced resistance to gastric acidification, and simultaneously evaluated the effect of antacid activity on the duodenal milieu. The model also permitted evaluation of the antacid effects of proteins (as natural antacids), and of drugs containing aluminium phosphate, alone or combined with magnesium oxide, or aluminium and magnesium hydroxides. At the gastric site, these drugs, as well as the proteins (that is, meat extract), induced a strong resistance to acidification due to the gastric emptying flux and to antacid composition. At the duodenal site, the decrease of the acid load penetrating into the duodenum varied, depending on the efficacy of gastric antacid activity. Duodenal pH was related to the equilibrium between bicarbonate secretion and the emptying of acid load. Proteins and aluminium phosphate induced the same duodenal pH as in the control tests without antacids, but magnesium-containing antacids increased it, thus decreasing bicarbonate consumption. The antacid mechanisms within the stomach, and the fate of antacids in the duodenal milieu, might explain the variation in duodenal pH in response to antacid administration.

Antacids↗

Raised concentrations of platelet activating factor in colonic mucosa of Crohn's disease patients.

Platelet activating factor (PAF-ACETHER or PAF) and precursors of platelet activating factor were investigated in 26 patients with acute Crohn's disease and in 10 healthy controls. Platelet activating factor, lyso platelet activating factor, and alkyl acyl glycerophosphocholine, were determined in colonic mucosal biopsies in patients with acute Crohn's disease, during prednisolone therapy, and in remission. Biopsy specimens were submitted to histopathology examination and to phospholipid extraction. Platelet activating factor, lyso platelet activating factor, and alkyl acyl glycerophosphocholine were found in patients with acute Crohn's disease and in remission as well as in controls. Whatever the site of the biopsy, the level of platelet activating factor in colonic mucosa was higher (p < 0.01) in Crohn's disease than in controls. There was no correlation between the level of colonic PAF-ACETHER and age, sex, Crohn's disease activity index, and biological parameters in sera. Although concentrations of colonic platelet activating factor content were higher (p < 0.01) when colonic mucosa displayed cell infiltration, they were neither related to the severity nor the type of inflammatory cells. Platelet activating factor decreases with prednisolone therapy and might return to normal concentrations in quiescent patients. Lyso platelet activating factor and alkyl acyl glycerophosphocholine were not significantly higher in Crohn's disease than in controls. These data suggest that platelet activating factor may be involved in the pathogenesis of Crohn's disease and that it could be used as a marker of the mucosal activity of the disease.

Adult↗

Influence of multiple endocrine neoplasia type 1 on gastric endocrine cells in patients with the Zollinger-Ellison syndrome.

The influences of multiple endocrine neoplasia type 1 (MEN 1), hypergastrinaemia, age, and sex on gastric endocrine cell densities were studied in 48 patients with the Zollinger-Ellison syndrome of either the sporadic type (n = 31) or associated with MEN 1 (n = 17). The mean fundic argyrophil cell density was higher in women (p < 0.05). It showed no appreciable difference between young and old women but it declined with age in men. The mean argyrophil cell density, when adjusted for sex, was higher (+48.5%, p = 0.06) in patients with Zollinger-Ellison syndrome associated with MEN 1 than in those with sporadic type disease. This measurement was not significantly different between the two groups of patients when antisecretory treatments were considered. In patients with sporadic type disease, fundic argyrophil cells showed a normal pattern (16%) or diffuse (71%) or linear (13%) hyperplasia. In patients with MEN 1 diffuse and linear hyperplasia were of the same order (53% and 47%). Furthermore, fundic argyrophil endocrine tumours developed in five of 17-that is, 29.5% of patients with associated MEN 1 while none was seen in patients with sporadic type disease. These tumours showed an exclusive or prominent enterochromaffin like cell population. Antral gastrin and somatostatin cell densities and fasting serum gastrin concentrations were similar in the two groups of patients with Zollinger-Ellison syndrome. Whatever the underlying mechanism for carcinoidosis, the risk of developing fundic enterochromaffin like cell tumours in Zollinger-Ellison syndrome patients who present with MEN 1 is probably higher than was initially estimated and suggests that regular follow up of these patients is necessary.

Adolescent↗

Biologic and immunologic gastrin activity in serum of patients with gastrinoma. Bioassay of gastrin activity in serum.

The biologic gastrin activity in serum from 14 patients with the Zollinger-Ellison syndrome was assessed by the stimulation of histamine release and acid secretion from the isolated vascularly perfused rat stomach and compared with the immunologic activity as determined by radioimmunoassay using an antibody directed towards the active site of the gastrin molecule. Biologic gastrin activity assessed by the stimulation of histamine release was more closely correlated to immunologic gastrin activity than biologic activity assessed by the stimulation of gastrin acid secretion. This study does not contradict the concept that gastrin stimulates acid secretion at least partly by releasing histamine and also shows that the immunologic gastrin activity determined with the help of an antibody directed towards the active site reflects biologic activity.

Aged↗

Evidence for the interaction between antacid and gastric mucosa using an "artificial stomach" model including gastric mucosa.

In light of evidence that certain aluminum-based antacids adhere to the gastric mucosa, we modified our previously described "artificial stomach" (AS) model by including a piece of hog stomach and compared the antacid activity of six aluminum-containing antacid products in the model with and without gastric mucosa. The activity of three of these, Maalox, Riopan and Supralox, was not significantly different in the two systems. In contrast, the activity of the other three, Aludrox, Phosphalugel and Simeco, was significantly greater with mucosa. Antacid activity of one product from each set (Supralox, Phosphalugel) was evaluated in two in vivo methods in human volunteers. For both antacids, results in vivo were similar to those obtained with the AS-containing mucosa. Without mucosa, in vivo and in vitro results were dissimilar for Phosphalugel, thus validating the modified AS. The difference between the two sets of antacids can be explained by 1) the fact that the Al:Mg ratio in the set affected by mucosa is greater than that of unaffected antacids, and 2) a weaker antacid load than in unaffected Supralox. We suggest that in an acid milieu, aluminum ions in antacids like Aludrox, Phosphalugel and Simeco are bound to sialic acid residues in mucus glycoproteins, thus retarding the transit of these antacids through both the AS and the real stomach and prolonging their activity in both situations. When the Al:Mg ratio is low or when the amount of antacid salts is large, aluminum ions tend to be buried in complexes, giving them less chance to interact with gastric mucus, so they transit the stomach more quickly.

Adult↗