Glucagon-like peptide-1-(7-36) amide, oxyntomodulin, and glucagon interact with a common receptor in a somatostatin-secreting cell line.

Glucagon-like peptide-1(7-36)amide (tGLP-1), oxyntomodulin (OXM), and glucagon are posttranslational end products of the glucagon gene expressed in intestinal L-cells. In vivo, these peptides are potent inhibitors of gastric acid secretion via several pathways, including stimulation of somatostatin release. We have examined the receptors through which these peptides stimulate somatostatin secretion using the somatostatin-secreting cell line RIN T3. tGLP-1, OXM, and glucagon stimulated somatostatin release and cAMP accumulation in RIN T3 cells to similar maximum levels, with ED50 values close to 0.2, 2, and 50 nM and 0.02, 0.3, and 8 nM, respectively. Binding of [125I]tGLP-1, [125I]OXM, and [125I]glucagon to RIN T3 plasma membranes was inhibited by the three peptides, with relative potencies as follows: tGLP-1 > OXM > glucagon. Whatever the tracer used, the IC50 for tGLP-1 was close to 0.15 nM and was shifted rightward for OXM and glucagon by about 1 and 2-3 orders of magnitude, respectively. Scatchard analyses for the three peptides were compatible with a single class of receptor sites displaying a similar maximal binding close to 2 pmol/mg protein. In the hamster lung fibroblast cell line CCL39 transfected with the receptor for tGLP-1, binding of [125I]tGLP-1 was inhibited by tGLP-1, OXM, and glucagon, with relative potencies close to those obtained with RIN T3 membranes. Chemical cross-linking of [125I]tGLP-1, [125I]OXM, and [125I]glucagon revealed a single band at 63,000 mol wt, the intensity of which was dose-dependently reduced by all three peptides. These data suggest that in the somatostatin-secreting cell line RIN T3, OXM and glucagon stimulate somatostatin release through a tGLP-1-preferring receptor. This suggests that some biological effects, previously described for these peptides, might be due to their interaction with this receptor.

Validation et normes du SF-36 dans la population du canton de Vaud

[Table des matières] 1. Patients et méthodes. 1.1. Enquête dans la population générale : population, modalités d'envoi, taux de réponse. 1.2. Questionnaire SF-36 et questionnaire Medical Outcome Study (MOS) : PF physical functioning = activité physique (fonctionnement) ; RP role physical = limitations (du rôle) liées à la santé physique ; BP bodily pain = douleur physique ; GH General Health = santé générale ; VT vitality = vitalité (énergie/fatigue) ; SF social functioning = fonctionnement ou bien-être social ; RE role éemotional = limitations (du rôle) liées à la santé mentale ; MH mental health = santé mentale ; CF cognitive functioning = fonctionnement cognitif (dimension absente du SF-36 classique) ; HT eported health transition = modification perçue de l'état de santé ("dimension" annexe, = item 2 ou Q2). 1.3. Analyse : calcul des scores du SF-36 et du SF-36 + CF, cohérence des réponses, fiabilité de l'instrument, validité. 1.4. Analyse statistique. 2. Résultats commentés de l'enquête dans la population générale. 2.1. Fréquence des non-réponses par item et par question. 2.2. Cohérence des réponses. 2.3. Scores d'état de santé par dimension : description et comparaison avec une population américaine, comparaison des scores vaudois et genevois. 2.4. Existe-t-il une concentration des bons et des mauvais scores chez les mêmes répondants ? 2.5. Fiabilité. 2.6. Validité : validité convergente et discriminante, analyse factorielle, validation en fonction de variables externes. 3. Discussion. 3.1. Evaluation du questionnaire. 3.2. Mesure de la qualité de vie liée à l'état de santé perçu dans la population générale. 3.3. Adjonction de la dimension "fonctionnement cognitif". 3.4. Conclusions et recommandations.

MOS-SF-36 in evaluating health-related quality of life in alcohol-dependent patients.

Health-related quality of life (HRQoL) was evaluated in a sample of alcohol-dependent patients with the 36-item Medical Outcome Study Short-Form Health Survey (MOS-SF-36). The instrument was administered to 147 patients (77% males), aged 26-78, with a DSM-III-R diagnosis of alcohol dependence. The Hamilton Depression Scale (HDS), the Severity of Alcohol Dependence Questionnaire (SADQ), and the Addiction Severity Index (ASI) were also administered to the first 100 patients included in the study. The reliability and validity of the MOS-SF-36 were evaluated. Test-retest intraclass coefficients for a 10-day interval were in the range .65 to .79, whereas the Cronbach alpha coefficient indicated good internal consistency (range .70 to .89). Compared to scores observed in the general population, MOS-SF-36 scores for alcohol-dependent patients were relatively low (indicating worse perception of HRQoL), especially in the psychological and role dimensions (range 52/100 to 55/100), but were closer to populational values in the physical and functional dimensions (range 61/100 to 75/100)). The highest correlation between MOS-SF-36 dimensions and HDS was found in the MOS-SF-36 "mental health" dimension (r=-.56, p < .001); this dimension was also correlated highly with the psychiatric dimension of the ASI (r=-.73, p < .001). The eight dimensions of the MOS-SF-36 were 21% to 127% lower in patients with HDS greater than or equal to 16 (major depression) compared to those with HDS less than or equal to 7 (absence of depression). The MOS-SF-36 dimensions were 10% to 141% lower in patients with high "ASI alcohol" scores, indicating worse HRQoL profiles with a higher severity of alcohol dependence. The MOS-SF-36 presents good criteria for reliability and validity in alcohol-dependent patients. The results suggested that alcohol-dependent patients perceived their problems more as psychological than physical. The severity of alcohol dependence and depression seemed to influence the perception of HRQoL negatively.

Millepertuis, corticoïdes, cocaïne, alcool ... et un premier épisode maniaque. Femme, 36 ans, artiste [St. John's Wort, corticosteroids, cocaine, alcohol ... and a first manic episode].

We describe an alcohol and cocaine abusing female patient who developed a first manic episode in the context of a corticosteroid prescription. The differential diagnoses are discussed on the basis of the available literature on secondary manias.

Endometrial cancer and oral contraceptives : an individual participant meta-analysis of 27 276 women with endometrial cancer from 36 epidemiological studies.

BACKGROUND: Oral contraceptives are known to reduce the incidence rate of endometrial cancer, but it is uncertain how long this effect lasts after use ceases, or whether it is modified by other factors. METHODS: Individual participant datasets were sought from principal investigators and provided centrally for 27 276 women with endometrial cancer (cases) and 115 743 without endometrial cancer (controls) from 36 epidemiological studies. The relative risks (RRs) of endometrial cancer associated with oral contraceptive use were estimated using logistic regression, stratified by study, age, parity, body-mass index, smoking, and use of menopausal hormone therapy. FINDINGS: The median age of cases was 63 years (IQR 57-68) and the median year of cancer diagnosis was 2001 (IQR 1994-2005). 9459 (35%) of 27 276 cases and 45 625 (39%) of 115 743 controls had ever used oral contraceptives, for median durations of 3·0 years (IQR 1-7) and 4·4 years (IQR 2-9), respectively. The longer that women had used oral contraceptives, the greater the reduction in risk of endometrial cancer; every 5 years of use was associated with a risk ratio of 0·76 (95% CI 0·73-0·78; p<0·0001). This reduction in risk persisted for more than 30 years after oral contraceptive use had ceased, with no apparent decrease between the RRs for use during the 1960s, 1970s, and 1980s, despite higher oestrogen doses in pills used in the early years. However, the reduction in risk associated with ever having used oral contraceptives differed by tumour type, being stronger for carcinomas (RR 0·69, 95% CI 0·66-0·71) than sarcomas (0·83, 0·67-1·04; case-case comparison: p=0·02). In high-income countries, 10 years use of oral contraceptives was estimated to reduce the absolute risk of endometrial cancer arising before age 75 years from 2·3 to 1·3 per 100 women. INTERPRETATION: Use of oral contraceptives confers long-term protection against endometrial cancer. These results suggest that, in developed countries, about 400 000 cases of endometrial cancer before the age of 75 years have been prevented over the past 50 years (1965-2014) by oral contraceptives, including 200 000 in the past decade (2005-14). FUNDING: Medical Research Council, Cancer Research UK.