Results of the Prolonged Use of Subcutaneous Continuous Infusion of Hydrocortisone in a Man with Congenital Adrenal Hyperplasia

This is a case report study of a young man with Congenital Adrenal Hyperplasia (CAH) who has been treated during 2 years by a subcutaneous continuous infusion hydrocortisone (SCIH) to optimize his treatment. Hydrocortisone was delivered via an insulin infusion device. We also studied the evolution of testicular adrenal rest tumors (TARTs) and the quality of life through SF36 survey. Four rates were determined, with a total of 47 mg per day. Biochemical parameters were normalized at 2 months. The SF36 questionnaire showed a progress of well-being. The weight decreased to 106 kg, that is, −5 kg (height: 1.71 m). Unfortunatly, there was no change of the TARTs. Two episodes of dermohypodermitis, with abscess at the infusion site, were observed. This case demonstrates the feasibility of prolonged SCIH therapy in patients with CAH, reporting positive effects on quality of life and on BMI

Education thérapeutique des patients diabétiques de type 2 : enquête auprès des patients diabétiques nouvellement diagnostiqués affiliés à la CPAM du Nord Finistère

BREST-BU Médecine-Odontologie (290192102) / SudocSudocFranceF

Effects of the route of oestrogen administration on IGF-1 and IGFBP-3 in healthy postmenopausal women: results from a randomized placebo-controlled study.

International audienceOBJECTIVE: Oestrogens can modulate the action or secretion of GH. Previous studies in postmenopausal women have shown a differential effect between transdermal 17beta-oestradiol and oral ethynyl-oestradiol on GH and IGF-1 concentrations. This secondary analysis, based on a large randomized trial, aimed to estimate the effect of the route of administration of 17beta-oestradiol in combined hormone replacement therapy with progesterone on IGF-1 and IGFBP-3 levels. DESIGN: IGF-1 and IGFBP-3 were evaluated in a randomized study of 196 healthy postmenopausal women who were randomly allocated to receive on a continuous basis either 1 mg of 17beta-oestradiol orally combined with a daily intake of 100 mg progesterone (group 1; n = 63), or 50 microg of 17beta-oestradiol transdermally combined with a daily intake of 100 mg progesterone (group 2; n = 68), or triple dummy placebo (group 3; n = 65) over a 6-month period. IGF1 and IGFBP-3 levels were available for 133 women. RESULTS: Oral oestrogen significantly decreased IGF-1 levels compared to placebo (P = 0.04) and transdermal oestrogen (P = 0.004), whereas transdermal oestrogen had no effect on IGF-1 levels compared to placebo (P = 0.56). As regards IGFBP-3, no significant difference was detected between the three groups. CONCLUSIONS: Our data indicate that the route of oestrogen administration can influence IGF-1 levels. IGF-1 concentrations decreased significantly with oral oestrogen, whereas no significant change was observed with transdermal oestrogen at 6 months. The clinical relevance of these differential effects remains to be determined, particularly with regard to the risk for cardiovascular diseases

Style et subjectivité

Dans son usage courant, le terme de style oscille entre la désignation d’un type (conformément à son origine rhétorique et aux styles étudiés par l’histoire de l’art) et la visée d’une singularité (dans le sillage de l’idée moderne du style propre d’un écrivain). Une telle ambiguïté empêche à la fois d’associer nécessairement le style à une subjectivité (comme celle de l’auteur, dont le style serait l’empreinte ou la signature) et d’écarter tout à fait du style le fantôme de la subjectivité qui le hante obstinément. La philosophie peut-elle penser le passage du style individuel au style collectif sans mobiliser l’Esprit hégélien ? Le programme phénoménologique de fondation du style dans la figure du sujet comme être-au-monde est-il à même d’y parvenir ? Ou faut-il renoncer au concept de sujet pour définir le style ? Les études ici rassemblées donnent à voir différents rapports ou absences de rapports du style à une subjectivité. De Husserl à Goodman, en passant par Heidegger, Merleau-Ponty, Maldiney et Foucault, que cherche et trouve la philosophie contemporaine dans le recours à l’idée de style ? En Varia, une traduction et un commentaire de la correspondance entre Ferdinand Tönnies et Carl Schmitt (1924-1930), ainsi qu’une étude sur la fondation par Husserl du concept tönnisien de communauté

Efficient synthesis of amino-protected calix[4]arenes selectively functionalized with iron chelator ICL670 designed as platform for iron recognition

International audienc

New piperazine-based siderophore-antibiotic conjugates to fight antimicrobial resistance

Fall National Meeting and Exposition of the American-Chemical-Society (ACS), San Diego, CA, AUG 25-29, 2019International audienc

Novel antimalarial enantiopure arylaminoalcohols as efflux pump substrates to fight resistant P. falciparum

International audienceMalaria still is one of the most threatening diseases in the world. In 2019, the WHO estimated 229 million of cases and 409,000 deaths mainly due to the most prevalent and lethal Plasmodium species: P. falciparum (Pf).Fighting resistant Pf strains is henceforth one of the main challenges to eradicate malaria. Indeed, parasites have developed resistances against all the available therapeutic arsenal, including artemisinin-based combination therapies (ACT). Studies of resistance phenotypes identified efflux pumps involved in this phenomenom of which the multidrug resistance ABC transporter PfMDR1. Its overexpression is partly responsible of the carrying of two ACT partner drugs, mefloquine (MQ) and lumefantrine (LM), into the food vacuole away from their cytosolic targets, leading to the efficacy decline of these arylaminoalcohol drugs.In order to limit this efflux, our laboratory has developed efflux pump inhibitor (EPI) patterns based on previous described resistance reversing agents such as penfluridol. A library of novel arylaminoalcohols is easily affordable into a previously optimized synthesis to obtain MQ, LM and enpiroline analogs. This stereoselective and convergent synthesis requires a key arylvinyl converted to the corresponding enantiopure aryloxirane thanks to a Sharpless asymmetric dihydroxylation followed by a one-pot cyclization. Finally, a regioselective ring-opening by EPI moieties led to efflux pump substrate compounds.Both design and synthesis of these arylaminoalcohols will be herein presented. In vitro efficacy against two Pf strains, cytotoxicity and preliminary results of P-gp, BCRP and MRPs efflux modulation in Caco-2 cells model will be reported. First structure-activity relationships will be discussed

Somatostatin receptor ligands induce TSH deficiency in thyrotropin-secreting pituitary adenoma

International audienc

Post-surgical management of non-functioning pituitary adenoma

Post-surgical surveillance of non-functioning pituitary adenoma (NFPA) is based on magnetic resonance imaging (MRI) at 3 or 6 months then 1 year. When there is no adenomatous residue, annual surveillance is recommended for 5 years and then at 7, 10 and 15 years. In case of residue or doubtful MRI, prolonged annual surveillance monitors any progression. Reintervention is indicated if complete residue resection is feasible, or for symptomatic optic pathway compression, to create a safety margin between the tumor and the optic pathways ahead of complementary radiation therapy (RT), or in case of post-RT progression. In case of residue, unless the tumor displays elevated growth potential, it is usually recommended to postpone RT until progression is manifest, as efficacy is comparable whether treatment is immediate or postponed. The efficacy of the various RT techniques in terms of tumor volume control is likewise comparable. RT-induced hypopituitarism is frequent, whatever the technique. The choice thus depends basically on residue characteristics: size, delineation, and proximity to neighboring radiation-sensitive structures. Reduced rates of vascular complications and secondary brain tumor can be hoped for with one-dose or hypofractionated stereotactic RT, but there has been insufficient follow-up to provide evidence. Somatostatin analogs and dopaminergic agonists have yet to demonstrate sufficient efficacy. Temozolomide is an option in aggressive NFPA resistant to surgery and RT.Après chirurgie, la surveillance des adénomes hypophysaires non fonctionnels (AHNF) repose sur l’imagerie par résonance magnétique (IRM) réalisée 3, voire 6 mois, puis un an après l’intervention chirurgicale. En l’absence de reliquat adénomateux, une surveillance annuelle est recommandée pendant 5 ans, puis 7, 10 et 15 ans après la chirurgie. En cas de reliquat ou d’image douteuse, une surveillance annuelle prolongée précisera l’évolutivité éventuelle de la lésion. Une seconde intervention chirurgicale est justifiée en cas de possibilité d’exérèse complète d’un reliquat, de compression symptomatique des voies optiques, afin de garder une distance de sécurité entre la tumeur et les voies optiques avant irradiation complémentaire ou en cas de progression tumorale après radiothérapie. En présence d’un reliquat, il est le plus souvent justifié (sauf si la tumeur manifeste un potentiel de croissance élevé) de différer la radiothérapie au moment où ce reliquat évolue, son efficacité étant comparable que le traitement soit réalisé d’emblée ou différé. L’efficacité des différentes techniques de radiothérapie sur le contrôle du volume tumoral est comparable. L’hypopituitarisme radio-induit est fréquent, quelle que soit la technique utilisée. Le choix dépendra donc essentiellement des caractéristiques du reliquat (taille, limites, proximité des structures radio-sensibles avoisinantes). Avec les radiothérapies stéréotaxiques en dose unique ou hypo-fractionnées, on espère une fréquence moindre des complications vasculaires et des rares tumeurs cérébrales secondaires ; mais le recul reste insuffisant. Les analogues de la somatostatine et les agonistes dopaminergiques n’ont pas fait la preuve jusqu’alors d’une efficacité suffisante. Le témozolamide peut être discuté chez les patients présentant des AHNF agressifs après chirurgie et radiothérapie