Progressive Retinal Atrophy in the Border Collie: A new XLPRA

<p>Abstract</p> <p>Background</p> <p>Several forms of progressive retinal atrophy (PRA) segregate in more than 100 breeds of dog with each PRA segregating in one or a few breeds. This breed specificity may be accounted for by founder effects and genetic drift, which have reduced the genetic heterogeneity of each breed, thereby facilitating the identification of causal mutations. We report here a new form of PRA segregating in the Border Collie breed. The clinical signs, including the loss of night vision and a progressive loss of day vision, resulting in complete blindness, occur at the age of three to four years and may be detected earlier through systematic ocular fundus examination and electroretinography (ERG).</p> <p>Results</p> <p>Ophthalmic examinations performed on 487 dogs showed that affected dogs present a classical form of PRA. Of those, 274 have been sampled for DNA extraction and 87 could be connected through a large pedigree. Segregation analysis suggested an X-linked mode of transmission; therefore both XLPRA1 and XLPRA2 mutations were excluded through the genetic tests.</p> <p>Conclusion</p> <p>Having excluded these mutations, we suggest that this PRA segregating in Border Collie is a new XLPRA (XLPRA3) and propose it as a potential model for the homologous human disease, X-Linked Retinitis Pigmentosa.</p

Methylation-associated PHOX2B gene silencing is a rare event in human neuroblastoma.

International audienceNeuroblastoma (NB), an embryonic tumour originating from neural crest cells, is one of the most common solid tumours in childhood. Although NB is characterised by numerous recurrent, large-scale chromosome rearrangements, the genes targeted by these imbalances have remained elusive. We recently identified the paired-like homeobox 2B (PHOX2B, MIM 603851) gene as disease-causing in dysautonomic disorders including Congenital Central Hypoventilation Syndrome (CCHS), Hirschsprung disease (HSCR) and NB in various combinations. Most patients with NB due to a germline heterozygous PHOX2B gene mutation are familial and/or syndromic. PHOX2B, at chromosome 4p12, does not lie in a commonly rearranged locus in NB. To evaluate the role of PHOX2B in sporadic, isolated NB, we analysed 13 NB cell lines and 45 tumours for expression, mutations of coding and promoter sequences, loss of heterozygosity (LOH), or aberrant hypermethylation of PHOX2B (13 cell lines and 18 tumours). We didn't identify any mutation but LOH in about 10% of the cases and aberrant CpG dinucleotide methylation of the 500 bp PHOX2B promoter region in 4/31 tumours and cell lines (12.9%). Altogether, both germinal and somatic anomalies at the PHOX2B locus are found in NB

Dépistage des troubles visuels de l'enfant (0 à 6 ans) par le médecin généraliste

AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Corps-objet ou corps-sujet? (Etude de cette dualité dans la relation du médecin au corps du patient à travers la représentation picturale)

AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocSudocFranceF

ETUDE ET COMPARAISON DES SYSTEMES DE SANTE DANS QUATRE PAYS D'EUROPE (ALLEMAGNE, ANGLETERRE, FRANCE ET PORTUGAL)

RENNES1-BU Santé (352382103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Approche globale de l'adolescent en consultation de médecine générale (difficultés, représentation)

INTRODUCTION: La médecine de l'adolescent est une discipline médico-psycho-social en différente de la pédiatrie et de la médecine adulte. L'objectif principal de notre étude est d'appréhender les différentes représentations, difficultés et mécanismes d'adaptation du médecin généraliste face à l'adolescent en consultation. METHODES: En basant notre étude sur la théorisation ancrée, nous avons réalisé des entretiens individuels de 10 médecins généralistes. Les entretiens ont été retranscrits manuellement, puis analysés selon 3 étapes (la codification des éléments, leur catégorisation la modélisation du phénomène) avant la phase de théorisation. RESULTATS: L'analyse de ces entretiens montre que l'accueil de l'adolescent est un schéma complexe, mêlant la contextualisation de la consultation, le raisonnement clinique, la qualité du rapport entre le médecin et l'adolescent et le choix des actions à mettre en œuvre. Dans ce cadre, le médecin cherche consciemment ou inconsciemment la meilleure conduite à tenir face à l'adolescent, que ce soit par la prise en charrge de la demande, par l'évaluation de la santé physique de l'adolescent, par la gestion du parent, ou par l'établissement d'un lien avec l'adolescent. CONCLUSION: Ce travail a permis de décrire la complexité de l'accueil de l'adolescent en médecine générale, ainsi que les facteurs influençant son déroulement. Comme dans les autres enquêtes réalisées sur ce sujet, il montre que les difficultés ressenties par les médecins généralistes face à l'adolescent sont situées à différents niveaux de la consultation, ce qui nous a permis de proposer des solutions afin de faciliter l'accueil de ce dernierAIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocSudocFranceF

Les Troubles spécifiques du langage chez l'enfant (enquête auprès des médecins généralistes d'Aix-en-Provence)

AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Preparation and evaluation of liposomes encapsulating synthetic MMP inhibitor (Ro 28-2653) - cyclodextrin complexes

peer reviewedIn this study, preparation and evaluation of liposomes, intended for intravenous administration, encapsulating synthetic MMP inhibitor (Ro 28-2653) - cyclodextrin complexes were realized. An increase in Ro solubility, via formation of binary (Ro/HP beta CD) or ternary (Ro/HP beta CD/L-lysine) complexes, permitted a similar increase in encapsulation efficiency of liposomes (Table 1). Moreover, Ro release kinetics depend on the encapsulation efficiency

Pharmacokinetic study of a new synthetic MMP inhibitor (Ro 28-2653) after IV and oral administration of cyclodextrin solutions

Ro 28-2653 (5-biphenyl-4-yl-5-[4-(4-nitro-phenyl)-piperazin-1-yl]-pyrimidine-2,4,6-trione) is a new synthetic inhibitor of matrix metalloproteinases (MMPs) with a high selectivity towards MMP2, MMP9 and membrane type 1-MMP. It has been shown that cyclodextrins (CDs) are able to form inclusion complexes with Ro 28-2653 and to increase its aqueous solubility. The aim of this study is to demonstrate that an increase in Ro 28-2653 solubility, via ternary complex formation, can lead to an increase in the oral bioavailability of this drug. This study shows that a synergistic effect exists between hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and L-lysine. The use of this multicomponent system enabled the preparation of oral and intravenous solutions of Ro 28-2653. In vivo evaluation of the oral solution of the inclusion complex of Ro 28-2653 in comparison with a suspension of the same uncomplexed drug showed a significant (p < 0.05) increase in absolute bioavailability. The area under curve (AUC) and the peak serum concentration (C-max) were approximately 10 times higher than those obtained with the suspension, while the time (T-max) to reach C-max was reduced. Moreover, in vivo administration of Ro 28-2653 solutions highlighted some information about the pharmacokinetic behavior of Ro 28-2653: a long biologic half-life (about 15.5 h) and a small overall volume of distribution (81). (c) 2006 Elsevier B.V. All rights reserved