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M Mignon

Publications and source records attributed to M Mignon.

At least 55 records · Page 3Linked to original sources
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

False-positive somatostatin receptor scintigraphy due to an accessory spleen.

A patient with previous left caudal pancreatectomy and splenectomy presented with Zollinger-Ellison syndrome. Abdominal CT and endoscopic ultrasonography revealed a mass in the splenic area. Somatostatin receptor scintigraphy showed a nodular increase of the uptake corresponding to the lesion detected with conventional imaging. A second laparotomy was performed and the mass was resected. Histological analysis showed that the nodular lesion was an accessory spleen. Since physiologic uptake of 111In-pentetreotide is seen in the spleen, an accessory spleen mimicking a tumor, specially after previous splenectomy, may result in false-positive somatostatin receptor scintigraphy.

False Positive Reactions↗
PubMed1997

[Detection of protein p53 in the stool of patients with colorectal cancer].

BACKGROUND AND AIMS: Mutations of TP53, a tumor suppressor gene, are found in 60% to 70% of colorectal cancers. These mutations usually induce an overexpression caused by modification of the p53 protein conformation. The aim of this study was to investigate whether stool specimens of patients with colorectal cancer contain increased amounts of p53 protein. METHODS: p53 protein was measured using a sandwich enzyme immunoassay in the stool specimens of 52 patients: 25 with colorectal cancer, 4 with colorectal adenomas and 23 apparently free of gastrointestinal disease. Results were expressed as pg/mg of total protein. The presence of fecal occult-blood was searched using Hemoccult II and Hemolex (an immunochemical assay for human hemoglobin). RESULTS: Median concentrations of stool p53 protein were 16.6 pg/mg (range: 0-591 pg/mg) in patients with colorectal cancers, 39.1 pg/mg (range: 5-72 pg/mg) in patients with adenomas and 5.9 pg/mg (range: 0-65 pg/mg) in control subjects. Resection of colorectal cancers caused a marked decrease of stool p53 protein concentrations. When the cut-off value for stool p53 protein was set at 60 pg/mg of fecal protein (concentrations over the 95th percentile), the positivity of the assay was independent of tumor size and Astler-Coller stage, but weakly associated with rectal location of cancer. The sensitivity of stool p53 protein for colorectal cancer was 44%, and the specificity was 96%. In contrast, the sensitivity of Hemoccult II and Hemolex tests was 48% and 44%, whereas their specificity was 91% and 96%, respectively. CONCLUSION: The detection of p53 protein is achievable in stool, but this assay is not more efficient than fecal occult blood tests for detection of colorectal cancer.

Adenocarcinoma↗
PubMed1996

Peritoneal carcinomatosis in patients with digestive endocrine tumors.

BACKGROUND: Peritoneal carcinomatosis (PC) in patients with digestive endocrine tumors (DET) is considered rare but its prevalence is unknown. The objectives of this study were to assess the prevalence and prognostic implications of PC in patients with various types of DET. METHODS: One hundred and sixteen consecutive patients with DET seen over a 3-year period were studied. Fifty-nine had gastrinomas, 30 had carcinoid tumors, and 27 had other types of endocrine tumors, mainly nonfunctioning ones. Diagnosis of PC was based on clinical symptoms (ascites and König's syndrome), findings of computed tomography scans that were performed at least yearly, and pathologic confirmation of tumor nodules or positive cytology in the peritoneal fluid. Factors associated with PC were investigated and the influence of PC on patients' survival was assessed. RESULTS: PC was found in 11 patients (overall PC prevalence: 10%; with 27% in patients with carcinoid tumors, 11% in those with nongastrinoma pancreatic endocrine tumors, and 0% in patients with gastrinomas). Nine of 11 patients with PC also had liver metastases. PC was metachronous to detection of the primary tumor in 7 of 11 patients, occurring 54 months (range, 23-273 months) after the diagnosis. In addition to the nature of the primary tumor, a greatest dimension of more than 5 cm was associated with the presence of PC in two of three patients with pancreatic endocrine tumors. In patients with carcinoid tumors, an ileal primary tumor occurred more frequently in patients with PC (87.5%) than in those without PC (50%). Prevalence of liver and other metastases was not significantly increased in patients with PC. Although five patients died of their disease, no deaths were related to PC. Actuarial survival rates at 5 years were 64% and 84% in patients with and without PC, respectively (P = not significant), whereas they were 73% and 93% in patients with and without liver metastases, respectively (P < 0.02). CONCLUSIONS: PC is not a rare event in the course of DET, especially in patients with carcinoid tumors. It did not occur in the patient population with gastrinomas, which are less often malignant but may also differ from the other types of DET by several cell characteristics. In contrast to liver metastases, PC is not associated with a significant decrease in life expectancy.

Actuarial Analysis↗
PubMed1996

[Detection of endocrine tumors of the digestive tract. Value and limitations of scintigraphy of somatostatin receptors].

Most neuroendocrin tumors (excepting insulinomas) carry a high density of somatostatin receptors which readily bind somatostatin analogs, allowing tumor and metastasis imaging with indium-labeled somatostasin analogs. For primary tumors (gastrinomas, carcinoid tumors), detection sensitivity is about 80%. The scintiscan adds complementary information to other imaging techniques including echoendoscopy. By combining indium-scan with echoendoscopy we have been able to detect 90% of the tumors in the upper duodenopancreatic area. In addition, scintigraphy detects tumors in about half of the patients with characteristic laboratory tests but negative imaging with other techniques. Metastases can also be detected; sensibility for liver is > 90%. The indium-scan is also positive in up to 20-30% of the patients after other imaging methods failed to identify metastasis. Finally, tumors found to be receptor-positive would respond better to treatment with somatostatin analogs.

Digestive System Neoplasms↗
PubMed1996

Preoperative detection of duodenal gastrinomas and peripancreatic lymph nodes by somatostatin receptor scintigraphy. Groupe D'etude Du Syndrome De Zollinger-Ellison.

BACKGROUND & AIMS: Duodenal gastrinomas and peripancreatic lymph nodes are difficult to localize. The aim of this study was to evaluate the ability of Octreoscan scintigraphy to detect such tumors. METHODS: Results of Octreoscan scintigraphy in 21 consecutive patients with Zollinger-Ellison syndrome were compared with those of conventional imaging techniques, including endoscopic ultrasonography, and with the surgical findings. RESULTS: Surgical exploration found 27 duodenal and/or lymph node gastrinomas in 19 patients. None had pancreatic gastrinoma. Octreoscan scintigraphy was the only positive preoperative technique in 32% of the patients. The sensitivities of conventional techniques, Octreoscan scintigraphy, and their association were 58%, 58%, and 90%, respectively, for all resected gastrinomas. The smallest duodenal gastrinoma detected by Octreoscan scintigraphy measured 3 mm. Endoscopic ultrasonography detected all the tumors visualized by any other conventional technique and was considered falsely positive, as was Octreoscan scintigraphy, in 1 patient. Follow-up and comparison between the number of resected gastrinomas and the number of preoperative hot spots suggested that surgeons should find at least as many tumors as the number of hot spots. CONCLUSIONS: Octreoscan scintigraphy improved the preoperative detection of extrapancreatic gastrinomas, mainly by endoscopic ultrasonography. Surgeons should find at least as many gastrinomas as the number of hot spots.

Adult↗
PubMed1996

Lanreotide inhibits human jejunal secretion induced by prostaglandin E1 in healthy volunteers.

1. Somatostatin inhibits hormonal secretions in the gastrointestinal tract. Somatostatin analogues are used in the treatment of VIPome-related watery diarrhoea. In addition, more than 10% of patients with AIDS suffer from diarrhoea likely due to the increased intestinal secretion of water and ions. However, the direct effect of somatostatin on the flux of water and ions in the intestine has not been, so far, analyzed in vivo. The aim of the present study was to evaluate the effect of lanreotide, a somatostatin analogue, on the movements of water and ions in the jejunum in man. 2. Accordingly, 10 healthy volunteers (age 18-35 years, mean 27) and two patients with AIDS (26 and 33 years) suffering from water diarrhoea (> 800 ml day-1) underwent intestinal perfusion using a four lumen tube with proximal occluding balloon. The segment tested was 25 cm long. The jejunum was infused by an isotonic control saline solution containing polyethylene glycol (PEG) as nonabsorbable marker. Basal jejunal secretions were measured in all subjects. Prostaglandin E1 (PGE1) was administered intraluminally to stimulate jejunal secretion in healthy volunteers. The effect of intravenous lanreotide on the jejunal PGE1-induced secretions of water and electrolytes was analysed in healthy subjects and on the basal secretions in AIDS patients. Each period was analyzed on the basis of three (10 min) successive intestinal juice collections after 20-30 min equilibration time. The antisecretory effect of lanreotide was evaluated in each subject as the difference between fluxes compared to the control period. 3. In healthy volunteers, PGE1 induced secretion of H2O, Na+, K+ and Cl- in the jejunum and lanreotide reduced significantly PGE1-induced response. In both AIDS patients basal fluxes of water and ions were reduced by lanreotide in a dose-dependent manner. 4. Somatostatin can reduce stimulated-jejunal secretion of ions and water in normal subjects and may improve water diarrhoea in AIDS patients.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Effect on gastric secretion, gastrin and histamine release during and after long-term treatment by pirenzepine in dogs.

We assessed the effects of pirenzepine (2 mg/kg per os) on gastric secretion and gastrin and histamine release in response to food and histamine dihydrochloride infusion in four dogs during 24 weeks of treatment and for 15 weeks after the end of treatment. The results were compared to those obtained in the same animals in control experiments, before treatment, and in four untreated dogs. Pirenzepine absorption was checked by measuring plasma concentrations. Pirenzepine led to a significant reduction in acid and pepsin secretion in response to histamine. In response to food, the reduction in secretion was concomitant with a reduction in gastrin and histamine release. Baseline concentrations of gastrin were reduced, while those of histamine were unchanged. No side effects were observed. After treatment, a long time lapse (about 15 weeks) was required for acid and pepsin secretion and gastrinemia to return to control levels, while histamine release in response to food normalized rapidly. Pirenzepine fixes selectively to M1 muscarinic receptors of the synaptic ganglion, thus inhibiting the effect of vagal stimulation, especially on pepsin secretion. Our data suggest that it might also fix to M1 receptors located on ECL cells, thereby reducing histamine release. In addition, pirenzepine probably fixes to other muscarinic receptors inhibiting gastrin release and resulting in a G and secretory cell mass reduction, probably by increasing somatostatin release.

Animals↗
PubMed1996

Oral calcium tolerance test in the early diagnosis of primary hyperparathyroidism and multiple endocrine neoplasia type 1 in patients with the Zollinger-Ellison syndrome. Groupe de Recherche et d'Etude du Syndrome de Zollinger-Ellison.

BACKGROUND: In patients with the Zollinger-Ellison syndrome, the exclusion of multiple endocrine neoplasia type 1 is of important clinical relevance. Its diagnosis often relies on the existence of primary hyperparathyroidism. AIM AND METHODS: To investigate the parathyroid function of patients with the Zollinger-Ellison syndrome by use of an oral calcium tolerance test to identify both hypercalcaemic and normocalcaemic primary hyperparathyroidism, and, accordingly, multiple endocrine neoplasia type 1. PATIENTS: Among 51 consecutive patients with the Zollinger-Ellison syndrome referred to us between 1988 and 1994, 28 had not been investigated for parathyroid function and were prospectively studied. RESULTS: The investigation of calcium metabolism was abnormal in nine patients. One displayed characteristic features of humoral hypercalcaemia of malignancy. The diagnosis of primary hyperparathyroidism was biologically established in eight patients (29%) and subsequently confirmed by the presence of hyperplasia of the parathyroid glands in the seven patients who underwent neck exploration. Three patients with primary hyperparathyroidism had fasting hyper-calcaemia but the other five had normal fasting serum total calcium concentration and the diagnosis of primary hyperparathyroidism was established by means of the oral calcium tolerance test. Primary hyperparathyroidism was demonstrated in the five patients in whom the diagnosis of multiple endocrine neoplasia type 1 had been previously established on other criteria than primary hyperparathyroidism. By contrast, in three patients, primary hyperparathyroidism, either hypercalcaemic (one patient) or normocalcaemic (two patients) was the sole criteria for the diagnosis of multiple endocrine neoplasia type 1. These results also suggest that primary hyperparathyroidism is present before or close to the time of Zollinger-Ellison syndrome diagnosis. CONCLUSION: Complete investigation of the parathyroid function with calcium calcium and parathyroid hormone concentrations.

Administration, Oral↗
PubMed1996

Glutamine synthetase induction by glucocorticoids is preserved in skeletal muscle of aged rats.

Glutamine synthetase (GS) is a glucocorticoid-inducible enzyme that has a key role for glutamine synthesis in muscle. We hypothesized that the glucocorticoid induction of GS could be altered in aged rats, because alterations in the responsiveness of some genes to glucocorticoids were reported in aging. We compared the glucocorticoid-induced GS in fast-twitch and slow-twitch skeletal muscles (tibialis anterior and soleus, respectively) and heart from adult (age 6-8 mo) and aged (age 22 mo) female rats. All animals received dexamethasone (Dex) in their drinking water (0.77 +/- 0.10 and 0.80 +/- 0.08 mg/day per adult and aged rat, respectively) for 5 days. Dex caused an increase in both GS activity and GS mRNA in fast-twitch and slow-twitch skeletal muscles from adult and aged rats. In contrast, Dex increased GS activity in heart of adult rats, without any concomitant change in GS mRNA levels. Furthermore, Dex did not affect GS activity in aged heart. Thus the responsiveness of GS to an excess of glucocorticoids is preserved in skeletal muscle but not in heart from aged animals.

Aging↗
PubMed1996

The use of new somatostatin analogues, lanreotide and octastatin, in neuroendocrine gastro-intestinal tumours.

In an open phase III study, octastatin was given as a continuous subcutaneous (s.c.) infusion to 35 patients (mean age 62 years) with malignant neuroendocrine gastro-intestinal tumours and the carcinoid syndrome. The wash-out was often incomplete because of the advanced stage of disease. The starting dose of 1.5 mg/24 h was increased up to 3.0 mg/24 h at 3 months in some patients. The carcinoid syndrome disappeared in 20% of patients at 3 months and in 23% at 6 months, with 43 and 45% of patients, respectively, experiencing an improvement. The mean Karnovsky index increased by > 10% in 40% of patients at 3 and 6 months. Urinary 5-hydroxyindoleacetic acid (U-5-HIAA) levels at 3 months normalised in 1 patient, fell in 20% (by > 50%; p = 0.0021) and stabilised in 66%. The respective values at 6 months were 1, 17% (p = 0.023) and 60%. There was also a significant decrease in plasma chromogranin levels at 3 months (p = 0.042), which did not persist at 6 months. Tumour size fell (by > 50%) in 1 patient by 6 months but this patient had undergone chemoembolisation one month prior to the start of the study. Most patients had tumour size stabilisation (76 and 68%) or progression (20 and 24%) at 3 and 6 months, respectively. Dose escalation from 1.5 to 3.0 mg did not significantly improve clinical, biochemical or tumour responses. The treatment was well tolerated with minor adverse events. In an open pilot phase II study of 19 patients (mean age 58 years), patients were given high dose somatuline with a maintenance dose of 12,000 mg/day in 4 divided s.c. injections. U-5-HIAA, which was elevated in 13 patients with a mean of 444 mumol/day before the start, was reduced to 58% of baseline at 3 months, 68% at 6 months (p = 0.04), 66% at 9 months and 75% at 12 months (p = 0.14). P-chromogranin was elevated in 18 patients, with a mean of 5,300 micrograms/l before the start, and was reduced to 52, 55, 63 and 64% of the baseline at 3, 6 (p = 0.039), 9 and 12 (p = 0.013) months, respectively. In the responding patients, apoptosis was induced.

Adult↗