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Biomedical subjects

M Mignon

Publications and source records attributed to M Mignon.

At least 181 records · Page 10Linked to original sources

[Diagnosis of glucagonoma. Value of scanning, echography and arteriography. Apropos of 2 cases and a review of the literature].

The authors report two cases of glucagonoma, a rare endocrine tumor of the pancreas, and describe the data currently found in literature. Glucagonoma is a single and usually large tumor, which develops in the alpha cells of the islets of Langerhans and evolves slowly. The combination of characteristic skin lesions, diabetes and weight loss should lead to searching for hyperglucagonemia and for the pancreatic tumor. The diagnosis is usually made rather late, average evolution is five years before diagnosis when it is detected. Imaging, in particular ultrasound and computed tomography (CT), proves to be necessary for the positive diagnosis of glucagonoma as it localizes the pancreatic mass and plays a role in local assessment, thus providing guidance for surgery. The role of imaging is also fundamental for the detection of metastases, which are the only sign of malignancy as no criterion of benignity is found for this tumor.

Adenoma, Islet Cell↗

[Tri-annual rhythm of basal acid secretion and secretion stimulated by pentagastrin in duodenal ulcer].

Duodenal ulcer is a recurrent disease with seasonal periodicity for pain and complications such as hemorrhage and perforation. Ulcer craters or symptoms seem to occur preferentially in early spring and autumn. Since acid secretion is one of the pathogenetic factors of the disease, we analyzed retrospectively basal and maximal (pentagastrin) acid secretion data obtained in 341 consecutive patients according to the month in which they were obtained. The patients were classified according to the activity of their ulcer (active, non active) and to the level of the peak acid secretion (hypersecretors, normosecretors). Basal acid concentration and output, and peak acid output were, both overall and month by month, higher in patients with active duodenal ulcer disease than in those who were non active, and in hypersecretors than in normosecretors. For all 341 patients as well as for normosecretors and non active ulcer patients, a triannual rhythm was detected for stimulated acid concentration and peak acid output. The highest values were noted in February, June, and October (period: 4 months). The amplitude of these rhythms was 3 to 4 percent, with differences between highest and lowest values of 30.4 mmol/l for concentration and 17.1 mmol/h for peak acid output. These rhythms for acid secretion during the year may contribute to the periodicity of duodenal ulcer events and should be analyzed in association with other factors which could be implied in ulcerogenesis. Moreover, this seasonal periodicity of acid secretion in duodenal ulcer should be taken into account in all therapeutic trials in which acid secretion is analyzed.

Adolescent↗

[Familial colonic cancer (Lynch's syndrome) and bile duct cancer. Study of 2 cases].

The authors describe two cases of bile duct carcinoma affecting two patients with hereditary non polyposis colorectal carcinoma (Lynch's syndrome). These two cases were observed in 14 families composed of 283 persons, 58 of whom were affected by hereditary non polyposis colorectal cancer and 15 by gynecological carcinomas. Bile duct carcinoma can therefore be associated with Lynch's syndrome but seems less frequent than observed in familial polyposis or Gardner's syndrome.

Adult↗

[Sigmoid motility stimulated by luminal distention. Changes in the motility response in constipation by the slowing down of left colonic transit].

The aim of our study was to develop a new technique of sigmoid manometry using standardized luminal distensions and to compare patterns of colonic motility following distension in normal subjects and in constipated patients. Eight subjects without colonic disturbances and 8 constipated patients with delayed transit time of the left colon as shown by radiopaque markers were investigated. Sigmoid motor activity was recorded by measuring pressure in a distending latex balloon placed at 25 cm from the anus. Inflations were maintained during 250 s and separated by 60 s recovery periods of deflation. Volumes of air (V) were increased until the patient reported abdominal pain (VMT). For each distension level, the resistance to distension of the bowel wall evaluated by the baseline adaptative pressure (P) and the contractile activity (A) quantified by planimetry of the active contractile activity (A) quantified by planimetry of the active contraction waves superimposed to P were assessed. In normal subjects, VMT was 147 +/- 9 ml. P increased linearly with V (p less than 0.03) up to 4,336 +/- 876 Pa. A increased with V until VMT/2 reached the maximum of 389 +/- 72 Pa*; for higher volumes A decreased significantly with to 166 +/- 46 Pa for VMT. Reference to controls, the constipated patients had a decreased VMT (61 +/- 4 ml). P increase at VMT (5,084 +/- 753 Pa) and A maximal value (387 +/- 176 Pa) were not different.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Sialic acid content and proteolytic activity in gastric juice in humans. An approach for appreciating mucus glycoprotein erosion.

The combined determination in human gastric juice of sialic acid content, a marker of solubilized glycoproteins, and of acidity and proteolytic activity has been performed in 217 gastric secretory studies. Taking 1000 micrograms/h of basal sialic acid output as approximating the upper limit of normal, 33 of 34 normal subjects and 12 of 12 patients without recurrent ulcer after highly selective vagotomy had basal sialic acid output below this value while 139 of 156 duodenal ulcer patients and 15 of 15 patients with Zollinger Ellison syndrome had basal sialic acid output above it. No clear relationship between sialic acid and hydrochloric acid outputs was observed; in contrast, close positive significant correlations were noted between sialic acid and pepsin outputs: r and P values ranging, respectively, from 0.82 to 0.63 and from less than 0.001 to less than 0.02. Measurement of sialic acid output content in basal secretion could thus serve to assess mucus glycoprotein output which appears, in large part, related to gastric juice proteolytic activity.

Duodenal Ulcer↗

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↗

A model of an 'artificial stomach' for assessing the characteristics of an antacid.

A model of an 'artificial stomach' has been constructed in order to take into account some of the parameters lacking in conventional in vitro antacid evaluation, namely the interaction between secretory flux and variation in emptying fluxes, the presence of proteins, and the use of human gastric juice instead of an aqueous solution of hydrochloric acid. The 'artificial stomach' has two elements, the 'stomach' and the pH recording system. The 'stomach' includes a 'gastric' reservoir receiving secretory flux and is emptied by variable fluxes. Aluminium phosphate gel has been studied in 100 ml of 0.1 N HCl, without and with 1 or 5% meat extracts and also in 100 ml of human gastric juice. The antacid effect of 1 or 5% meat extracts has also been assessed. The antacid effect of aluminium phosphate was characterized by the pH rise of the 'gastric' contents, the buffering capacity, and the dilution of gastric contents. These factors were modulated by emptying fluxes. The same characteristics were found when antacid was studied in gastric juice. Proteins exerted a neutralizing effect and modified aluminium phosphate's antacid capacity. A mechanism for buffering capacity by cation aluminium is suggested.

Antacids↗

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↗

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↗

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↗

[Characterization and evaluation of the pathogenic nature of duodenogastric reflux by measurement of intragastric choline and sialic acid in normal subjects and in patients with duodenal ulcer].

The high choline content in pancreatic juice and bile-contaminated gastric juice samples suggested that intragastric choline content could be related to duodenogastric reflux (DGR). In 308 secretory tests in normal subjects (38) and in duodenal ulcer patients (DU) (270), acid, pepsin, sialic acid and choline outputs were measured in basal secretion and after pentagastrin, insulin or secretin modulation. The distribution of choline output values in basal secretion showed that 77% subjects had no or small choline amounts (less than 10 mumol/h) and another population had high output values (greater than or equal to 10 mumol/h). Choline hourly outputs greater than or equal to 10 mumol/h could be related with positive DGR. DGR did not seem to modify acid or pepsin secretion except if acid outputs were low: in these cases the neutralizing activity reduced acid outputs and resulted in a pepsin inactivation. DGR by itself increased sialic acid outputs as evidenced by mucus erosion. In normal subjects, weak mucus erosion might be due to proteolytic activity. In DU patients without DGR, erosion was increased but was due to the same mechanism. In DU patients with DGR, erosion was stronger and no relationship with proteolytic activity could be established because of the introduction of eroded duodenal glycoprotein into the stomach. Pentagastrin, insulin and secretin were able to induce DGR. Reflux could contribute to mucus erosion either by its detersive properties or by the proteolytic material coming from the pancreas.

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↗