Hypoleptinemia in patients with anorexia nervosa: loss of circadian rhythm and unresponsiveness to short-term refeeding.

Leptin is a protein encoded by the ob gene that is expressed in adipocytes and regulates eating behavior via neuroendocrine mechanisms. Plasma leptin levels have been shown to correlate with weight and body fat in normal, obese and anorexic subjects. In the last of these populations, the dynamic profile of plasma leptin levels during short-term refeeding has never been assessed. We thus investigated basal plasma leptin levels in 29 female patients with anorexia nervosa (AN) (age 21.9 +/- 1.4 years, body mass index (BMI) 15.2 +/- 0.3 kg/m2) and in 80 normal female controls (age 21.2 +/- 0.2 years, BMI 20.3 +/- 0.3 kg/m2, mean +/- S.E.M.). Basal plasma leptin levels in AN were decreased by 77% compared with controls (2.5 +/- 0.2 vs 11.1 +/- 0.7 ng/ml, P < 0.0001). In both AN subjects and controls, plasma leptin levels correlated significantly with BMI (r2 = 0.448, P < 0.0001 and r2 = 0.339, P < 0.0001 respectively). Five AN patients (four female, one male, age 22.0 +/- 4.7 years, BMI 14.2 +/- 0.4 kg/m2, body fat 4.3 +/- 0.9 kg or 11.0 +/- 1.9% of body weight, basal metabolic rate (BMR) 958 +/- 122 kcal/day) were studied during a 3-day refeeding period and compared with eight control subjects (two male, six female, age 25.7 +/- 1.2 years, BMI 21.3 +/- 0.8 kg/m2, body fat 15.1 +/- 0.9 kg or 24.6 +/- 1.7%, BMR 1455 +/- 78 kcal/day) submitted to 36-h fasting. The amount of calories administered was based on BMR + 20% (carbohydrate 60%, protein 17%, fat 23%). In contrast to the rise in leptin levels that occurred during refeeding after a prolonged fast period in normal subjects, plasma leptin levels remained low and unchanged throughout the 3 days of renutrition in AN patients. The circadian rhythm of leptin was also completely abolished. This contrasted with the preserved circadian variations of cortisol, whose mean levels were increased. In conclusion, we confirmed that plasma leptin levels are low in AN and correlate with body weight. We further demonstrated that plasma leptin levels do not respond to short-term refeeding in anorexic patients in whom circadian variations are not restored, which suggests that the acute regulation of leptin by positive changes in energy balance is not preserved under a critical threshold of body fat

Long-term reduction of microalbuminuria after 3 years of angiotensin-converting enzyme inhibition by perindopril in hypertensive insulin-treated diabetic patients.

We studied the long-term effects of the angiotensin-converting enzyme (ACE) inhibitor perindopril, administered for 36 months on glycemic control, creatinine clearance, and albuminuria in hypertensive insulin-treated diabetics. After 1 month treatment with placebo, 39 patients entered the study and received 4-8 mg perindopril/day. Within the first 3 months, diastolic blood pressure was normalized in 80% of the patients. From these, 23 were followed during a total of 3 years on perindopril therapy, and divided in three groups according to their initial urinary albumin excretion rate (AER): 11 had normal AER (less than 15 mg/24 hours), eight had microalbuminuria (AER 15-150 mg/24 hour), and four had AER greater than 150 mg/24 hours and had overt proteinuria. Long-term (3 years) diastolic blood pressure normalization (less than or equal to 90 mm Hg) was achieved throughout the study. Concomitant with blood pressure reduction, a long-term decrease in AER was observed in normo- and microalbuminuric patients. Macroproteinuria was unaffected by perindopril. Glycemic control and creatinine clearance remained stable during the whole study period. No major side effects were observed. We conclude that perindopril safely produces a long-term normalization of elevated blood pressure in hypertensive insulin-treated diabetics without affecting glycemic control. Blood pressure normalization is associated with long-term AER reduction in normo- and microalbuminuric patients

Unilateral retinoblastoma, lack of familial history and older age does not exclude germline RB1 gene mutation.

Conclusive identification of RB1 mutations in retinoblastoma is predicted to improve the clinical management of affected children and relatives. However, despite clear clinical benefits, RB1 screening remains difficult, most of the alterations being unique and randomly distributed throughout the entire coding sequence. In this report, we present the results of a constitutional RB1 analysis undertaken in our institution over the last four years. The detection of RB1 gene deletion or mutation was performed by Southern blot and sequence analyses in 73 patients (including three families with 2, 3 and 3 probands, respectively). Complementary constitutional chromosome and fluorescent in situ hybridization (FISH) analyses of RB1 gene were applied in cases where hereditary retinoblastoma was suspected despite negative detection. Altogether, germline abnormalities were found in 11% (4/36 patients) of sporadic unilateral retinoblastoma (median age, 21.5 months) and 86% (32/37 patients) of sporadic bilateral or positive familial history retinoblastoma (median age, 5 months). The spectrum of germline alterations found in 31 distinct families included 12 nonsense mutations (39%); 10 point insertions or deletions with frameshift (32%); 4 mutations and 1 deletion affecting splice sites (16%); 2 missense mutations (6%); and 2 large deletions (6%). A total of 15 mutations have not been previously reported. In this small series, splicing mutations were associated with bilateral disease whilst most of the frameshift mutations were identified in patients with an early age at diagnosis, bilateral disease or hereditary forms of the disease. This study confirms that screening for constitutional RB1 mutation should become an integral part of current management of any patient affected by retinoblastoma irrespective of the tumour laterality and familial background

Comparative conformational analysis of two endothelin-B antagonists

A comparative conformational analysis of two short pseudopeptides with ETB receptor affinity has been performed by molecular modelling and NMR techniques. This analysis aimed to get insight into probable biorelevant conformations and pharmacophoric patterns necessary for an efficient interaction with the receptor. Thus, it was shown that the two compounds can adopt γ-turn (or γ-turn-like) conformations, based on which the synthesis of particular, more rigid analogs might be proposed. The results obtained should prove valuable in a strategy aiming to design new endothelin antagonists following a peptide to non-peptide approach. © 1995 ESCOM Science Publishers B.V.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Circadian and circannual variations in cord blood hematopoietic cell composition

SCOPUS: le.jinfo:eu-repo/semantics/publishe

Nouveautés en endocrinologie, diabétologie et nutrition: que retenir de 2016?

À l’instar des années précédentes, l’année 2016 a été riche de nouveautés et d’innovations diagnostiques et thérapeutiques dans les domaines des pathologies endocriniennes, du diabète et des maladies métaboliques. Nous avons volontairement choisi de n’illustrer ici que celles qui, aujourd’hui déjà, ont modifié la prise en charge de ces pathologies, que ce soit par le médecin spécialiste ou le médecin généraliste. Tous les lecteurs devraient donc y trouver quelque intérêt. Ainsi dans le domaine du diabète, nous vous parlons de la nouvelle convention INAMI, d’un nouveau système remboursé de mesure en continu du taux de glucose interstitiel par capteur, des progrès technologiques impressionnants des nouvelles pompes à insuline ainsi que des bénéfices importants de l’utilisation des inhibiteurs des transporteurs SGLT-2 (les ‘glucorétiques’) en termes de complications cardiovasculaires et rénales chez le patient diabétique de type 2. Au plan des pathologies métaboliques, les inhibiteurs de la PCSK9 sont maintenant remboursés dans l’hypercholestérolémie familiale hétérozygote et certains analogues du GLP-1 sont disponibles pour un traitement efficace de l’obésité. Dans le domaine des pathologies thyroïdiennes, l’hypothyroxinémie maternelle isolée de la grossesse est aujourd’hui mieux caractérisée et de nouvelles recommandations ont été émises en 2016 concernant le diagnostic et le traitement de l’ophtalmopathie thyroïdienne. Enfin, concernant l’endocrinologie générale, de nouvelles recommandations clarifient et simplifient la prise en charge de l’incidentalome surrénalien dont la fréquence de découverte ne fait que croître, à l’ère d’une imagerie abdominale de plus en plus performante[Innovations in endocrinology, diabetology, and nutrition: what 2016 brought us ?] The year 2016 was again full of novelties, with numerous diagnostic and therapeutic innovations in the fields of endocrine diseases, diabetes, and metabolic disorders. In this article, we deliberately chose to only discuss those which have already improved the current management of such diseases, be it for specialists or general practitioners. The article should therefore be interesting for every reader. In the field of diabetes, we have here reported on the main features of the new agreement between social security system, physicians, and diabetic patients (“Convention INAMI”). We have also reported on a newly reimbursed system for continuous measurement of interstitial glucose through a sensor, on the impressive technological advances in modern insulin pumps, as well as on the significant cardiovascular and renal benefits of SGLT2 transporter inhibitors in Type 2 diabetes patients. As for metabolic pathologies, the PCSK9 inhibitors are now reimbursed in heterozygous familial hypercholesterolemia, and specific GLP-1 analogues are available for an effective treatment of obesity. In the field of thyroid diseases, isolated maternal hypothyroxinemia during pregnancy is now better characterized, and new recommendations have been issued regarding the diagnosis and treatment of Grave’s ophthalmopathy. Finally, as regards general endocrinology, new recommendations clarify and simplify the management of adrenal incidentaloma, whose detection frequency continually increases in the era of common and more efficient abdominal imaging

L'invention du solitaire

L’invention du solitaire : laissons jouer le double sens du titre. Comment et pourquoi le solitaire s’invente-t-il à une période de l’histoire (littéraire) et qu’invente-t-il ? A la première question, il faut répondre en périodisant l’histoire des rapports entre écrivain et solitaire. À la deuxième, on peut plus brutalement répondre : ce que le solitaire invente, c’est la littérature - dans son sens moderne. L’antinomie première que nous ne cesserons de voir est la suivante : comment être et se sentir seul, alors que cette pensée se dit par les mots, c’est-à-dire par ce qui est social en soi ? Comment affirmer son irréductible singularité avec les mots de tous ? Envisager l’histoire de cette invention, c’est donc faire la généalogie de cette nouvelle figure, qui recoupe en partie l’histoire des modalités formelles de la Modernité et de ses contradictions. Les études réunies dans ce livre sont articulées en trois moments. Le premier temps ne peut faire l’économie d’un retour à Rousseau, qui change la donne de la solitude dans ses rapports avec l’écriture. Mais Rousseau reste ambivalent face à ce qu’il découvre malgré lui ; ce sont ses héritiers qui infléchissent dans un certain sens sa découverte. Exaltation de l’esseulement, perte des repères historiques, accentuation du divorce avec la société : tels sont les traits analysés de Zimmermann à Senancour, de Chateaubriand à Lamartine et Vigny, de Rabbe à Thoreau. Le deuxième moment est compris dans le premier mais Baudelaire lui confère son sens nouveau. Changement de décor avant tout : c’est dans la grande ville, dans les foules que le solitaire habite maintenant ; il y côtoie l’anonyme multitude. Contre le romantisme, la littérature moderne cherche les voies d’une essentielle dépersonnalisation, la figure presque anonyme du solitaire, d’Amiel à Flaubert, de Lautréamont à Huysmans ou Bloy - tandis que la percée du monologue souterrain défait la possibilité d’une solitude unifiée, des premiers coups portés par Dostoïevski à ceux de des Forêts, Nabokov et Beckett. La période contemporaine hérite alors de cette contradiction fondamentale : isolé et séparé, le sujet l’est sans pouvoir fonder aucune autarcie souveraine. Monade, chaque être vivant l’est par son exister mais cette solitude est prise dans la série des autres solitudes, semblables et différentes. De Camus à Genet, de Cohen à Perec, ou encore de Saint-John Perse à Sylvie Germain et Tabucchi, nous en décrivons le trajet - avant de voir dans le tueur en série une des figures les plus terribles du solitaire, à la mesure de notre société actuelle

Deuil et littérature

La tâche du deuil ? « Maintenir vivant comme objet perdu » celui ou celle que nous avons perdu. C’est-à-dire : ne pas fantasmer son improbable survie, sans céder non plus à l’effacement de l’oubli, cette deuxième mort symbolique, presque plus terrible que la première réelle. Est-ce cela que la littérature nous permet, ou plus modestement nous promet ? Une reconnaissance et une conversion de la perte, qui composerait avec la dimension mélancolique en y échappant ? L’objet de ce livre est plutôt de laisser résonner cette question, d’en suivre le trajet sur deux siècles et dans certaines œuvres majeures de la modernité. De nouer des fils, d’ouvrir des pistes, de mettre en écho du début du xixe siècle jusqu’à des textes tout à fait contemporains cette problématique union, cette tension constitutive entre deuil et écriture. Pour être fidèles à ce qui pourrait être la définition même de la littérature : l’incessant dialogue entre les vivants et les morts

Sempre los camps auràn segadas resurgantas

Professeur émérite de l’Université de Toulouse-Le Mirail, ancien directeur de recherches au CNRS. Xavier RAVIER est d’abord un dialectologue. Disciple de Jean Séguy, il a réalisé l’Allas linguistique et ethnographique du Languedoc occidental. Auteur de 1res nombreuses publications, il a toujours manifesté une curiosité scientifique et un esprit d’ouverture remarquables. Ses recherches l'ont ainsi conduit, au-delà de la linguistique, vers l’ethnolinguistique et plus particulièrement l'ethnolittérature, mais aussi l’onomastique, l’édition et l’étude de textes occitans non littéraires du Moyen Age, la littérature occitane et française, la poétique enfin. Ces Mélanges sont une occasion de rendre hommage à la richesse et à la diversité de la production scientifique d’un chercheur qui a toujours privilégié l’innovation et le dialogue entre disciplines

High Risk of Anal and Rectal Cancer in Patients With Anal and/or Perianal Crohn’s Disease

International audienceBackground & AimsLittle is known about the magnitude of the risk of anal and rectal cancer in patients with anal and/or perineal Crohn’s disease. We aimed to assess the risk of anal and rectal cancer in patients with Crohn’s perianal disease followed up in the Cancers Et Surrisque Associé aux Maladies Inflammatoires Intestinales En France (CESAME) cohort.MethodsWe collected data from 19,486 patients with inflammatory bowel disease (IBD) enrolled in the observational CESAME study in France, from May 2004 through June 2005; 14.9% of participants had past or current anal and/or perianal Crohn’s disease. Subjects were followed up for a median time of 35 months (interquartile range, 29–40 mo). To identify risk factors for anal cancer in the total CESAME population, we performed a case-control study in which participants were matched for age and sex.ResultsAmong the total IBD population, 8 patients developed anal cancer and 14 patients developed rectal cancer. In the subgroup of 2911 patients with past or current anal and/or perianal Crohn’s lesions at cohort entry, 2 developed anal squamous-cell carcinoma, 3 developed perianal fistula–related adenocarcinoma, and 6 developed rectal cancer. The corresponding incidence rates were 0.26 per 1000 patient-years for anal squamous-cell carcinoma, 0.38 per 1000 patient-years for perianal fistula–related adenocarcinoma, and 0.77 per 1000 patient-years for rectal cancer. Among the 16,575 patients with ulcerative colitis or Crohn’s disease without anal or perianal lesions, the incidence rate of anal cancer was 0.08 per 1000 patient-years and of rectal cancer was 0.21 per 1000 patient-years. Among factors tested by univariate conditional regression (IBD subtype, disease duration, exposure to immune-suppressive therapy, presence of past or current anal and/or perianal lesions), the presence of past or current anal and/or perianal lesions at cohort entry was the only factor significantly associated with development of anal cancer (odds ratio, 11.2; 95% CI, 1.18-551.51; P = .03).ConclusionsIn an analysis of data from the CESAME cohort in France, patients with anal and/or perianal Crohn’s disease have a high risk of anal cancer, including perianal fistula–related cancer, and a high risk of rectal cancer