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M Mignon

Publications and source records attributed to M Mignon.

At least 37 records · Page 2Linked to original sources

Effect of psyllium on gastric emptying, hunger feeling and food intake in normal volunteers: a double blind study.

OBJECTIVE: To assess whether psyllium, a soluble dietary fibre, could, at an acceptable dose (7.4 g), delay gastric emptying of a low-calorie meal, and reduce hunger feeling and energy intake, without requiring intimate mixing with the meal. DESIGN: A double blind randomized cross over study with 14 normal volunteers, to evaluate the effect of this dose of psyllium on postprandial serum glucose, triglycerides and insulin levels, and on gastric fullness, hunger feeling and food intake. METHODS: Gastric emptying was measured using a standard double-radiolabeled 450 kcal meal and feelings by visual analogic scales. The postprandial serum glucose, triglycerides and insulin levels were also determined. RESULTS: No delay in the gastric emptying of the solid and liquid phases of the meal was observed with psyllium. After the meal, hunger feelings and energy intake were significantly lower during the psyllium session than during the placebo session (13% and 17% lower respectively; P < 0.05). Postprandial increase in serum glucose, triglycerides and insulin levels was less with psyllium than with placebo (P < 0.05). CONCLUSIONS: Psyllium reduces hunger feelings and energy intake in normal volunteers at reasonable dose and without requiring mixing with the meal. It does not act by slowing down the gastric emptying of hydrosoluble nutrients, but by increase in the time allowed for intestinal absorption, as suggested by the flattening of the postprandial serum glucose, insulin and triglycerides curves.

Adolescent↗

Diagnostic and therapeutic criteria in patients with Zollinger-Ellison syndrome and multiple endocrine neoplasia type 1.

About 25% of patients with ZES have MEN-1. Except for diarrhoea, less frequent in patients with ZES MEN-1 than in sporadic ZES, and specific MEN-1-related signs, clinical characteristics are similar in both ZES types. Acid output and gastrin level are also similar whether in the basal state or after secretin. Primary hyperparathyroidism (pHPT) exists in the majority of ZES MEN-1 patients, 30% have pituitary adenoma (prolactinomas for half), 30% adrenal involvement, 25-30% have ECLomas: bronchial and thymic carcinoids have probably been underevaluated. Gastrinomas are multiple predominantly located in the duodenal wall, but also in the pancreas in association with clinically silent endocrine tumours. The spread of the disease metastases to the liver (LM), mediastinum, bones, is evaluated best by Octreoscan. Associated endoscopic ultrasonography evaluates the number, size and anatomical characteristics of gastrinomas. Patients without LM have an excellent prognosis. Surgery never cures ZES, but is necessary in cases of associated life-threatening conditions such as insulinoma. Although the size of the tumour, when located in the pancreas >3 cm, favours metachronous LM occurrence, surgery in our experience has not been able to prevent LM development.

Diagnosis, Differential↗

pH is regulated differently by glucose in skeletal muscle from fed and starved rats: a study using 31P-NMR spectroscopy.

The aim of this study was to determine whether exogenous glucose metabolism influences the pH in superfused EDL muscle from growing rats fed or starved for 48 h (body weight 55 and 45 g, respectively). Energy state and intracellular pH of muscle were repeatedly monitored by 31P-nuclear magnetic resonance spectroscopy (31P-NMRS); glycogen and other energy metabolites were assayed enzymatically in muscle extracts at the end of the experiment. In EDL muscles from starved rats superfused with glucose for 4 h, intracellular pH was elevated (7-7.3), lactate concentration low, glycogen repletion very intense and citrate synthase activity high. We conclude that glucose was routed mainly toward both oxidative phosphorylation and glycogen synthesis in EDL muscles after food deprivation of rats. In contrast, the major pathway in muscles from fed rats may be glycolysis because the glycogen pool remained constant throughout the experiment. The additional and minor pH component (in the range of 6.5 to 6.8) seen in muscles from fed rats, even in the presence of exogenous glucose, might be due to impaired glucose utilization because this component appears also in muscles from starved rats superfused without glucose or with a nonmetabolizable analog of glucose. Consequently, direct pH measurement by 31P-NMR may be considered to be a precise criterion for evaluation of differences in metabolic potentialities of muscle studied ex vivo in relation to the nutritional state of rats.

Adenosine Triphosphate↗

A diffuse T lymphocytic gastrointestinal mucosal infiltration associated with Sjögren's syndrome resulting in a watery diarrhea syndrome and responsive to immunosuppressive therapy.

We report the case of a 45-yr-old white man, investigated for chronic diarrhea, malabsorption and weight loss associated with sicca syndrome. Endoscopic and x-ray examinations showed normal macroscopic mucosa in gastrointestinal tract (GIT). Immunohistochemistry showed diffuse polyclonal T cell lymphocytes infiltrating either epithelium and lamina propria in GIT. There was no villous atrophy in the jejunum and ileum. Corticosteroids, azathioprine, and cyclosporine failed to improve symptoms. Monthly intravenous cyclophosphamide administered over 1 yr, stopped the diarrhea and weight loss. The patient is free of symptoms up to a 5-yr follow-up.

Cell Movement↗

[Clinicogenetic study of MEN1: recent physiopathological data and clinical applications. Study Group of Multiple Endocrine Neoplasia (GENEM)].

Multiple Endocrine Neoplasia type 1 (MEN1, OMIM 131100, Wermer syndrome) is characterized by inherited predisposition to primary hyperparathyroidism, endocrine pancreatic-duodenal, pituitary, adrenal glands tumors and benign and/or malignant proliferations of diffuse neuroendocrine tumors in thymus and bronchi, formerly defined as carcinoid tumors. Minor lesions have been observed in MEN1 patients such as cutaneous tumors (angiofibroma, lipoma, lentiginosis), thyroid epithelioma and tumors of the central nervous system, mainly spinal ependymoma. The MEN1 gene, a locus encompassing a 9 kb of genomic sequence contains 10 exons, the first exon being untranslated. The protein encoded by this gene was called menin and has been shown to contain two nuclear localization signals (NLS), suggesting a major function in the nucleus. Germline MEN1 mutations have been described in more than 150 families and are spread throughout the entire coding sequence. More than 70% of the mutations alter one or both NLS and no genotype-phenotype correlations were found to date. The MEN1 gene seems to be involved in a 20-30% of sporadic parathyroid and pancreatic/bronchic neuroendocrine tumors, but less than 1% of pituitary sporadic tumors. Further knowledge on the intracellular function of menin will be needed to understand the pathogenic effect of truncating and missense mutations of this gene in the initiation of endocrine cells tumorigenesis.

Humans↗

[Effectiveness and safety of lansoprazole in the treatment of Zollinger-Ellison syndrome. First six months of treatment].

OBJECTIVES: The aim of this prospective study was to confirm the efficacy and safety of lansoprazole in patients with Zollinger-Ellison syndrome (ZES). METHODS: Fourteen patients (5 W, 9 M) with ZES, age (mean +/- SD) 55.5 +/- 12.8 years, were included in the study. STUDY DESIGN: initially and at 1, 3 and 6 months thereafter the following items were assessed: clinical signs, fasting serum gastrin (FSG), basal acid output (BAO) before next dose of lansoprazole. BAO < 10 mmol H+/h was considered as efficient. Initially and at 6 months, laboratory tests (hematology, liver, renal and hormonal), endoscopy and histological enterochromaffin-like cell and gastrin cell density assessments were performed. Lansoprazole initial dose was adjusted according to clinical symptoms and secretory studies. RESULTS: At 6 months, lansoprazole doses of 60, 90, 120 and 180 mg/d maintained BAO < 10 mmol H+/h in 9, 2, 1 and 1 patient, respectively. No significant changes in FSG, endocrine cells densities and biological parameters were noted during treatment. Neither adverse events nor carcinoid tumors were observed. We conclude that lansoprazole is efficient and well tolerated in patients with ZES.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Contribution of proteolysis and de novo synthesis to alanine production in diabetic rat skeletal muscle: a 15N/1H nuclear magnetic resonance study.

To assess the role of leucine as a precursor of alanine alpha-amino nitrogen in skeletal muscle during diabetes, extensor digitorum longus muscles from control (n = 7 experiments) and streptozotocin-diabetic rats (n = 8 experiments) were isolated and superfused with [15N]leucine (3 mmol/l) in the presence of glucose (10 mmol/l) for 2 h. Muscle perchloric acid extraction was performed at the end of superfusion in order to quantify newly synthesized alanine by 15N/1H nuclear magnetic resonance. Release of [15N]alanine in the superfusion medium was also measured. The pool of newly synthesized [15N]alanine was significantly increased (approximately 40%) in extensor digitorum longus muscles from streptozotocin-diabetic rats. Whereas a significant enhancement of total alanine release from muscle was induced by diabetes (20%), only a slight increase in [15N]alanine release was detectable under our experimental conditions. Consequently, we conclude that streptozotocin-diabetes in growing rats induces in skeletal muscle: 1) an increase in nitrogen exchange between leucine and alanine leading to newly synthesized [15N]alanine; and 2) an increase of total alanine release from muscle originating from both proteolysis and de novo synthesis.

Alanine↗

Somatostatin receptor subtype gene expression in human endocrine gastroentero-pancreatic tumours.

Somatostatin and its analogues are now of current use in the management of endocrine gastroentero-pancreatic (GEP) tumours for the purpose of inhibiting hormone hypersecretion, carrying scintigraphy imaging and attempting to slow down tumour growth. Recent molecular studies have revealed the existence of up to five membrane somatostatin receptor subtypes termed SSTR1-5. However, whether or not scintigraphy imaging and tumour characteristics are correlated with specific subtype(s) remains unclear. SSTR1-5 messenger RNA (mRNA) transcripts were investigated in 38 endocrine GEP tumours (32 islet cell tumours, six carcinoid) using reverse transcriptase polymerase chain reaction (RT-PCR), and their distribution was analysed with respect to tumour characteristics and scintigraphy imaging. SSTR2, SSTR5 and SSTR4 were detected in most cases of endocrine GEP tumours (92%, 84%, and 82% respectively), but SSTR1 and SSTR3 were less frequently observed (66% and 50% respectively). No clear-cut correlation was found between tumour characteristics and subtype mRNA distribution. Moreover, no differences in mRNA subtype distribution were found between the 17 tumours detected by scintigraphy and the four tumours not detected by this method. Somatostatin receptor mRNA subtypes are widely expressed in endocrine GEP tumours, but their distribution is not correlated with tumour characteristics or scintigraphy positivity.

Adenoma, Islet Cell↗

Refeeding improves muscle performance without normalization of muscle mass and oxygen consumption in anorexia nervosa patients.

The effect of starvation-related malnutrition on muscle performance and on the energy cost of exercise remains unknown, as does the timing of improvement by refeeding. Indeed, in most diseases that induce malnutrition, muscle dysfunction is worsened by an inflammatory process. Thus, physical performance and the energy cost of exercise were studied in 15 semistarvated malnourished anorexia nervosa (AN) patients during exercise on an ergometric bicycle (3-min steps of 30 W) before and after 8, 30, and 45 d of refeeding. Results were compared with those of 15 normal-weight healthy subjects matched for age, sex, and physical activity. Before refeeding, the workload reached during the exercise was 49% lower in AN patients than in control subjects (P < 0.01). It was correlated with body weight, fat-free mass, and leg muscle circumference (P < 0.002). The performance improved dramatically during refeeding (P < 0.03), reaching normal values after 45 d of refeeding, despite fat-free mass and leg muscle circumference values that were still 20% lower in AN patients than in control subjects (P < 0.01). At this time, the exercise-related VO2 remained unchanged, being approximately 25% lower than that of the control subjects when corrected for muscle mass differences (P < 0.03). In conclusion, in AN patients muscle performance was restored by refeeding long before the patients achieved normal nutritional status. The economic cost of physical activity for these malnourished patients allows them to maintain a relatively high level of physical activity. This relative overactivity has two goals in AN: it reinforces anorexia and contributes to the excess of energy expenditure needed for weight loss.

Adult↗

Heterogeneity of tbpB, the transferrin-binding protein B gene, among serogroup B Neisseria meningitidis strains of the ET-5 complex.

ET-5 complex strains of Neisseria meningitidis were traced intercontinentally and have been causing hyperendemic meningitis on a worldwide scale. In an attempt to develop a fully broad cross-reactive transferrin-binding protein B (TbpB)-based vaccine, we undertook to assess the extent of variability of TbpB proteins among strains of this epidemiological complex. For this purpose, a PCR-based method was developed to study the heterogeneity of the tbpB genes from 31 serogroup B N. meningitidis strains belonging to the ET-5 complex. To define adequate primers, the tbpB gene from an ET-5 complex strain, 8680 (B:15:P1.3; isolated in Chile in 1987), was cloned and the nucleotide sequence was determined and compared to two other previously published tbpB sequences. A tbpB fragment was amplified from genomic DNA from each of the 31 strains. By this method, heterogeneity in size was observed and further characterized by restriction pattern analysis with four restriction enzymes and by sequencing tbpB genes from three other ET-5 complex strains. Four distinct tbpB gene types were identified. Fifty-five percent of the strains studied (17/31) harbored tbpB genes similar to that of strain BZ83 (B:15:-) isolated in The Netherlands in 1984. Ten of the 31 strains (32.2%) had tbpB genes close to that of strain M982. Only 3 of the 31 (9.6%) were found to harbor tbpB genes close to that of strain 8680, and finally one strain, 8710 (B:15:P1.3; isolated in Chile in 1987), was found to harbor a tbpB gene different from all the others. These results demonstrated a pronounced variability among tbpB alleles within a limited number of ET-5 complex strains collected over a 19-year period. Despite the genetic heterogeneity observed, specific antisera raised to purified Tbps from ET-5 complex strains showed broad cross-reactivity between different TbpBs both by Western blot analysis and bactericidal assay, confirming that a limited number of TbpB molecules included in a vaccine are likely to induce broadly cross-reactive antibodies against the different strains.

Antigens, Bacterial↗

Evaluation of recombinant transferrin-binding protein B variants from Neisseria meningitidis for their ability to induce cross-reactive and bactericidal antibodies against a genetically diverse collection of serogroup B strains.

Transferrin-binding protein B (TbpB) is a surface-exposed protein, variable among strains of Neisseria meningitidis, that has been considered as a vaccine candidate. To define a TbpB molecule that would give rise to broadly cross-reactive antibodies with TbpB of many strains, specific antisera were produced against three recombinant TbpB variants from strain M982: one corresponding to the full-length TbpB; one in which stretches of amino acids located in the central part of the molecule, described as hypervariable, have been deleted; and one corresponding to the N-terminal half of the molecule, described as the human transferrin binding domain. The reactivity of these antisera against 58 serogroup B strains with a 2.1-kb tbpB gene representing different genotypes, serotypes, and subtypes and different geographic origins was tested on intact meningococcal cells. In parallel, the bactericidal activity of the antisera was evaluated against 15 of the 58 strains studied. Of the 58 strains, 56 (98%) reacted with the antiserum specific for the N-terminal half of TbpB M982; this antiserum was bactericidal against 9 of 15 strains (60%). On the other hand, 43 of 58 strains reacted with the antiserum raised to full-length TbpB while 12 of 15 (80%) were killed with this antiserum. The antiserum specific to TbpB deleted of its central domain gave intermediate results, with 53 of 58 strains (91.3%) recognized and 10 of 15 (66.6%) killed. These results indicate that the N-terminal half of TbpB was sufficient to induce cross-reactive antibodies reacting with the protein on meningococcal cells but that the presence of the C-terminal half of the protein is necessary for the induction of cross-bactericidal antibodies.

Antibodies, Bacterial↗

Identification of human transferrin-binding sites within meningococcal transferrin-binding protein B.

Transferrin-binding protein B (TbpB) from Neisseria meningitidis binds human transferrin (hTf) at the surface of the bacterial cell as part of the iron uptake process. To identify hTf binding sites within the meningococcal TbpB, defined regions of the molecule were produced in Escherichia coli by a translational fusion expression system and the ability of the recombinant proteins (rTbpB) to bind peroxidase-conjugated hTf was characterized by Western blot and dot blot assays. Both the N-terminal domain (amino acids [aa] 2 to 351) and the C-terminal domain (aa 352 to 691) were able to bind hTf, and by a peptide spot synthesis approach, two and five hTf binding sites were identified in the N- and C-terminal domains, respectively. The hTf binding activity of three rTbpB deletion variants constructed within the central region (aa 346 to 543) highlighted the importance of a specific peptide (aa 377 to 394) in the ligand interaction. Taken together, the results indicated that the N- and C-terminal domains bound hTf approximately 10 and 1000 times less, respectively, than the full-length rTbpB (aa 2 to 691), while the central region (aa 346 to 543) had a binding avidity in the same order of magnitude as the C-terminal domain. In contrast with the hTf binding in the N-terminal domain, which was mediated by conformational epitopes, linear determinants seemed to be involved in the hTf binding in the C-terminal domain. The host specificity for transferrin appeared to be mediated by the N-terminal domain of the meningococcal rTbpB rather than the C-terminal domain, since we report that murine Tf binds to the C-terminal domain. Antisera raised to both N- and C-terminal domains were bactericidal for the parent strain, indicating that both domains are accessible at the bacterial surface. We have thus identified hTf binding sites within each domain of the TbpB from N. meningitidis and propose that the N- and C-terminal domains together contribute to the efficient binding of TbpB to hTf with their respective affinities and specificities for determinants of their ligand.

Animals↗

Multivariate analysis of pathophysiological factors in reflux oesophagitis.

BACKGROUND: Reflux oesophagitis is considered a multifactorial disease, but the respective roles of the main factors involved in its pathophysiology have not been clearly established. AIMS: To attempt to assign these roles by means of a multivariate logistic regression analysis of the main parameters associated with reflux oesophagitis. PATIENTS: Eighty seven patients with gastro-oesophageal reflux disease were studied: 41 without oesophagitis and 46 with reflux oesophagitis grade 1 to 3. METHODS: (1) Monovariate comparison of patients' characteristics and of parameters derived from in hospital 24 hour oesophageal pH monitoring, oesophageal manometry, double isotope gastric emptying studies, and basal and pentagastrin stimulated gastric acid and pepsin output determinations, between patients with and without oesophagitis. (2) Multivariate logistic regression analysis including the parameters significant in the monovariate analysis. RESULTS: Among the 16 significant parameters from monovariate analysis, three significant independent parameters were identified by multivariate logistic regression analysis: number of refluxes lasting more than five minutes, reflecting oesophageal acid clearance (p = 0.002); basal lower oesophageal sphincter pressure (p = 0.008); and peak acid output (p = 0.012). These three parameters were not correlated with each other. The multivariate model was highly discriminant (correct classification of 81.3% of the cases (95% confidence intervals 0.723, 0.903). Risk for oesophagitis increased as a function of the tercile threshold values of the three parameters. Odds ratios of the three parameters for oesophagitis risk were similar, regardless of whether they were calculated when the patients were compared as a function of oesophagitis grade or the presence or absence of oesophagitis. CONCLUSIONS: This multivariate approach adds evidence that impaired oesophageal acid clearance and hypotonic lower oesophageal sphincter are the two major independent pathophysiological factors of oesophagitis, but also showed that the acid secretion level is an independent pathophysiological factor.

Adult↗

Usefulness of somatostatin receptor scintigraphy in the management of patients with Zollinger-Ellison syndrome. Groupe de Recherche et d'Etude du Syndrome de Zollinger-Ellison (GRESZE).

BACKGROUND: Management of patients with Zollinger-Ellison syndrome (ZES) depends on the presence of multiple endocrine neoplasia type 1 (MEN 1) or liver metastases, or both. Somatostatin receptor scintigraphy (SRS) detects previously unknown endocrine tumours. AIM AND METHODS: To evaluate SRS findings susceptible to modifying the management of patients with ZES-that is, relevant findings, and the specificity of these findings. The latter were defined according to our current therapeutic strategy in three subgroups of patients (sporadic, MEN 1, and liver metastases). PATIENTS: 85 consecutive patients without known extra-abdominal metastases were studied between September 1991 and March 1996. RESULTS: Relevant findings were found in 41% of 49 patients with sporadic disease but without liver metastases, in 22% of 18 patients with MEN 1 but without liver metastases, and in 17% of 18 patients with liver metastases. Follow up was available for 20 (74%) of 27 patients who had 23 relevant findings. Nineteen relevant findings (83%) were confirmed at a median of three (range 0.25-45) months of follow up; four (17%) were not confirmed at 30 (range 12-52) months (p = 0.025). Findings located in the duodenopancreatic area (90%), chest (100%), bone (100%), and liver (60%) were confirmed. Most findings for patients with MEN 1 involved the chest. CONCLUSION: SRS detects many anomalies susceptible to modifying management of patients with ZES, especially in those with sporadic disease. The specificity of hot spots located outside the liver seems very high. By contrast, the specificity of hot spots located in the liver remains to be evaluated when conventional imaging is negative.

Adult↗

Parathyroid hormone-related protein in an esophageal squamous cell carcinoma with tumor-induced hypercalcemia.

Cancers from patients with tumor-induced hypercalcemia usually produce a circulating factor that mimics the parathyroid hormone activity, termed parathyroid hormone-related protein. Incidence of tumor-induced hypercalcemia appears to be high in patients with squamous cell carcinoma of the esophagus, and the presence of parathyroid hormone-related protein have been shown in some primary esophageal cancers. In the present study, we have investigated the presence of parathyroid hormone-related protein in a patient with metastasized squamous cell carcinoma of the esophagus complicated with tumor-induced hypercalcemia. Protein was searched by immunohistochemistry, and messenger RNA was investigated by reverse transcriptase-polymerase chain reaction and S1 nuclease assay. Both messenger RNA and protein were detected in hepatic metastases, whereas normal esophageal mucosa and primary cancer did not express detectable protein or messenger RNA using the S1 nuclease assay. Reverse transcriptase-polymerase chain reaction was positive in all these tissues, including normal esophageal mucosa. In conclusion, the present case suggests that tumor-induced hypercalcemia due to esophageal squamous cell carcinoma may be caused by parathyroid hormone-related protein mostly released by liver metastases.

Carcinoma, Squamous Cell↗

Clinical impact of somatostatin receptor scintigraphy in the management of patients with neuroendocrine gastroenteropancreatic tumors.

UNLABELLED: Somatostatin receptor scintigraphy (SRS) has been used for the detection of gastroenteropancreatic (GEP) tumors. This study evaluates the clinical impact of SRS in GEP tumor detection and its therapeutic implications on patient management. METHODS: We prospectively studied 160 patients with biologically and/or histologically proven GEP tumors. Before SRS, patients were classified into three groups: gastrointestinal (Group 1; n = 90) patients without known metastases; (Group 2; n = 59) patients with metastases limited to the liver; (Group 3; n = 11) patients with known extrahepatic metastases. The scintigraphic data were compared to the radiological findings. RESULTS: In Group 1, without known metastases, conventional imaging detected 53 primary sites in 44 patients: SRS was positive in 68% of these sites and discovered 4 additional primary tumors in 3 patients and 16 metastases in 14 patients. Conventional imaging was negative in 46 patients: SRS discovered 47 new sites in 36 patients. In Group 2, SRS confirmed liver metastases in 95% of patients and discovered 45 new sites in 36 of these patients. In Group 3, SRS disclosed 11 new sites in 7 patients. These results modified patient classification in 38 cases (24%). Surgical therapeutic strategy was changed in 40 patients (25%). CONCLUSION: Somatostatin receptor scintigraphy improves tumor detection, has major clinical significance and should be performed systematically for staging and therapeutic decision making in patients with GEP tumors.

Carcinoid Tumor↗