Paradoxical embolism following thromboaspiration of an arteriovenous fistula thrombosis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Paradoxical embolism is an increasingly reported cause of arterial embolism. Several embolic sources have been described, but thrombosis of an arteriovenous fistula as a paradoxical emboligenic source has not, to the best of our knowledge, been reported.</p> <p>Case presentation</p> <p>A 50-year-old Caucasian woman received a renal graft for primary hyperoxaluria. After transplantation, she was maintained on daily hemodialysis. Thrombosis of her arteriovenous fistula occurred two weeks post-transplantation and was treated by thromboaspiration, which was partially successful. During a hemodialysis session immediately following thromboaspiration, she developed a coma with tetraplegia requiring intensive cardiorespiratory resuscitation. Brain magnetic resonance imaging revealed various hyperdense areas in the vertebrobasilar territory resulting from bilateral occlusion of posterior cerebral arteries. Transesophageal echocardiographic examination showed a patent foramen ovale, while pulse echography of the arteriovenous fistula revealed the persistence of extensive clots that were probably the embolic source. A paradoxical embolus through a patent foramen ovale was suggested because of the proximity of the neurological event to the thrombectomy procedure.</p> <p>Conclusions</p> <p>The risk of paradoxical embolism in a hemodialyzed patient with a patent foramen ovale deserves consideration and requires careful evaluation in situations of arteriovenous fistula thrombosis.</p

Ankyrin G restricts ion channel diffusion at the axonal initial segment before the establishment of the diffusion barrier

Ion channel immobilization by ankyrin G is regulated by casein kinase 2 in immature hippocampal neurons

Self-reported data: a major tool to assess compliance with anti-malarial combination therapy among children in Senegal

Background: Although there are many methods available for measuring compliance, there is no formal gold standard. Different techniques used to measure compliance were compared among children treated by the anti-malarial amodiaquine/sulphadoxine-pyrimethamine (AQ/SP) combination therapy, in use in Senegal between 2004 and 2006. Methods: The study was carried out in 2004, in five health centres located in the Thies region (Senegal). Children who had AQ/SP prescribed for three and one day respectively at the health centre were recruited. The day following the theoretical last intake of AQ, venous blood, and urine samples were collected for anti-malarial drugs dosage. Caregivers and children above five years were interviewed concerning children's drug intake. Results: Among the children, 64.7% adhered to 80% of the prescribed dose and only 37.7% were strict full adherent to the prescription. There was 72.7% agreement between self-reported data and blood drug dosage for amodiaquine treatment. Concerning SP, results found that blood dosages were 91.4% concordant with urine tests and 90% with self-reported data based on questionnaires. Conclusion: Self-reported data could provide useful quantitative information on drug intake and administration. Under strict methodological conditions this method, easy to implement, can be used to describe patients' behaviors and their use of new anti-malarial treatment. Self-reported data is a major tool for assessing compliance in resource poor countries. Blood and urine drug dosages provide qualitative results that confirm any drug intake. Urine assays for SP could be useful to obtain public health data, for example on chemoprophylaxis among pregnant women

Pharmacogenetic profiling and cetuximab outcome in patients with advanced colorectal cancer

<p>Abstract</p> <p>Background</p> <p>We analyzed the influence of 8 germinal polymorphisms of candidate genes potentially related to EGFR signalling (<it>EGFR</it>, <it>EGF</it>, <it>CCND1</it>) or antibody-directed cell cytotoxicity (<it>FCGR2A </it>and <it>FCGR3A</it>) on outcome of colorectal cancer (CRC) patients receiving cetuximab-based therapy.</p> <p>Methods</p> <p>Fifty-eight advanced CRC patients treated with cetuximab-irinotecan salvage therapy between 2001 and 2007 were analyzed (mean age 60; 50 PS 0-1). The following polymorphisms were analyzed on blood DNA: <it>EGFR </it>(CA repeats in intron 1, -216 G > T, -191C > A, R497K), <it>EGF </it>(A61G), <it>CCND1 </it>(A870G), <it>FCGR2A </it>(R131H), <it>FCGR3A </it>(F158V). Statistical analyses were conducted on the total population and on patients with wt KRas tumors. All SNPs were considered as ternary variables (wt/wt <it>vs </it>wt/mut <it>vs </it>mut/mut), with the exception of -191C > A <it>EGFR </it>polymorphism (AA patient merged with CA patients).</p> <p>Results</p> <p>Analysis of skin toxicity as a function of EGFR intron 1 polymorphism showed a tendency for higher toxicity in patients with a low number of CA-repeats (p = 0.058). <it>CCND1 </it>A870G polymorphism was significantly related to clinical response, both in the entire population and in KRas wt patients, with the G allele being associated with a lack of response. In wt KRas patients, time to progression (TTP) was significantly related to <it>EGFR </it>-191C > A polymorphism with a longer TTP in CC patients as compared to others, and to <it>CCND1 </it>A870G polymorphism with the G allele being associated with a shorter TTP; a multivariate analysis including these two polymorphisms only retained <it>CCND1 </it>polymorphism. Overall survival was significantly related to <it>CCND1 </it>polymorphism with a shorter survival in patients bearing the G allele, and to <it>FCGR3A </it>F158V polymorphism with a shorter survival in VV patients (in the entire population and in KRas wt patients). <it>FCGR3A </it>F158V and <it>CCND1 </it>A870G polymorphisms were significant independent predictors of overall survival.</p> <p>Conclusions</p> <p>Present original data obtained in wt KRas patients corresponding to the current cetuximab-treated population clearly suggest that <it>CCND1 </it>A870G polymorphism may be used as an additional marker for predicting cetuximab efficacy, TTP and overall survival. In addition, <it>FCGR3A </it>F158V polymorphism was a significant independent predictor of overall survival.</p

Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors

CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that CD25 expression is largely restricted to tumor-infiltrating Treg cells in mice and humans. While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor (FcγR) IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models. Use of an anti-CD25 antibody with enhanced binding to activating FcγRs led to effective depletion of tumor-infiltrating Treg cells, increased effector to Treg cell ratios, and improved control of established tumors. Combination with anti-programmed cell death protein-1 antibodies promoted complete tumor rejection, demonstrating the relevance of CD25 as a therapeutic target and promising substrate for future combination approaches in immune-oncology

Evaluation d'un projet de réseau de Médecins Correspondants du SAMU dans 4 secteurs de grande ruralité de Corse du Sud (Ota, Cargèse, Vico, Haut-Taravo)

Par quatre études, un projet de réseau de médecins correspondants du SAMU dans les secteurs de grande ruralité de Ota, Cargèse, Vico et Haut-Taravo en Corse du Sud est évalué: Le recueil des données des feuilles d'intervention des MCS de Haute-Savoie montre que le réseau est efficace, évite une intervention SMUR dans 61,5% des cas, et est très interventionnel: utilisation de morphine IV, médicaments spécialisés.Le premier questionnaire aux médecins de secteurs corses montre qu'ils ont une pratique proche de ceux de Haute-Savoie, sans conventionnement ni formation spécifique, en relation avec les casernes de pompiers, dont le maillage est important. Le questionnaire aux membres des instances de pilotage et de concertation de Corse montre une tendance à un vote en faveur d'un tel projet. Le second questionnaire aux médecins ruraux corses, montre qu'ils sont motivés pour la création d'un réseau, que la formation spécialisée les intéresse, surtout si des intervenants peuvent se déplacer lors des réunions de formation continue, que l'uniformisation d'un matériel d'urgence est possible, et que la rémunération n'est pas un motif majeur de revendication. Les obstacles majeurs à un tel projet restent les distances lointaines à parcourir le manque de médecins pour remplir des tableaux de garde. Des projets de l'ARS sont à l'étude pour améliorer ces deux points: la taille des secteurs pourront être revus en concertation avec les médecins du réseau, des aides financières sont envisagées pour inciter des médecins à s'installer. Une évaluation du réseau dans quelques années permettrait de confirmer son efficacité.AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocSudocFranceF

L'effet du vieillissement sur la microcirculation cutanée

The pressure application on the skin leads to an increase of the cutaneous blood flow, called pressure-induced vasodilatation (PIV), that delays the occurrence of tissue ischemia resulting from this pressure. The development of this PIV depends on the activation by pressure of sensory C-fibres, leading to the release of neurotransmitters that acts at the endothelium level to stimulate the synthesis and release of endothelial factors inducing smooth muscle relaxation. This work had for objective to study the modifications of the PIV with the ageing. In old mice, without peripheral neuropathy, the PIV was reduced because of a decrease of the endothelium-dependent vasodilatation and the endothelium factors of the vasodilatation were redistributed with a contribution of Endothelium-Derived Hyperpolarizing Factor because of a decrease of the nitric oxide and the prostacyclin. In old subjects (60-75 years), the PIV was altered in comparison with young subjects (20-35 years) because of a decrease of the endothelium-dependent vasodilatation and a sensory fibres and/or neuromediators alteration. In the presence of a peripheral neuropathy, the PIV was abolished. These modifications of the cutaneous microcirculation with the ageing would lead to an early occurrence of ischemia related to an increased risk for pressure ulcers and the understanding of PIV modifications allow to glimpse of news perceptives of prevention and treatment of pressure ulcers in elderlyL'application d'une pression sur la peau provoque une vasodilatation cutanée, appelée vasodilatation induite par une pression (PIV), et retarde l'apparition de l'ischémie tissulaire liée à cette pression. La pression appliquée sur la peau active les fibres nerveuses capsaïno-sensibles, qui sécrètent en réponse des neurotransmetteurs, qui eux provoquent au niveau de l'endothélium la synthèse et la sécrétion de facteurs endothéliaux qui induisent une relaxation du muscle lisse. Ce travail avait pour objectif d'étudier l'effet du vieillissement sur la PIV.Chez la souris âgée, sans neuropathie périphérique, la PIV était altérée en raison d'une diminution de la vasodilatation endothélium-dépendante ; et la contribution des facteurs endothéliaux de la vasodilatation était modifiée : l'Endothelium-Derived Hyperpolarizing Factor jouait un rôle primordial en raison d'une diminution du monoxyde d'azote et de la prostacycline. Chez les sujets âgés (60-75 ans), la PIV était altérée en comparaison avec les sujets jeunes (20-35 ans) en raison d'une diminution de la vasodilatation endothélium-dépendante mais aussi d'une altération des fibres capsaïno-sensibles et/ou des neurotransmetteurs. En présence d'une neuropathie périphérique, la PIV était abolie. Ces modifications de la microcirculation cutanée au cours du vieillissement expliqueraient la plus grande vulnérabilité de la peau à l'ischémie et l'augmentation du risque d'ulcère de pression liée à l'âge. La compréhension des modifications de la PIV avec l'âge permet d'entrevoir de nouvelles perceptives de prévention et de traitement de l'ulcère de pression chez le sujet âgé

Suivi de modèles uniques à l'aide de nanocristaux semiconducteurs (méthodes et application à l'étude de la dynamique du récepteur de la glycine)

Le suivi de molécules uniques est utile pour comprendre le déroulement d un processus biologique. Il permet de sonder des propriétés dynamiques inaccessibles pas des mesures d ensemble. Nous présentons les nanocristaux semiconducteurs et montrons qu ils permettent de combiner les avantages des autres marqueurs fluorescents avec une grande photostabilité et un très bon rapport signal à bruit. Nous exposons une approche de suivi automatique dédiée à ces nano-objets scintillants. Nous discutons les méthodes spécifiquement adaptées à l analyse des trajectoires ainsi obtenues. Nous appliquons ces techniques d imagerie ultrasensible à l étude de la dynamique membranaire du récepteur de la glycine (RGly) dans les milieux vivants. Nous présentons une étude sur l implication du cytosquelette dans la régulation du nombre de RGly aux synapses. Nous examinons les interactions entre le RGly et la géphyrine (sa protéine d ancrage) dans des systèmes cellulaires modèles et caractérisons l équilibre correspondant.Single molecule tracking experiments are useful to understand biological processes since they give access to dynamic properties which are inaccessible with ensemble measurements. We present the properties of semiconductor quantum dots (QDs) and show how their superior brightness and photostability enable ultrasensitive biological imaging. Next, we introduce a new approach for automatically tracking QD-labeled membrane molecules which accounts for the blinking of the fluorescent probes and we discuss methods specifically adapted to analyse the obtained trajectories. Finally, we apply these sensitive imaging techniques to study glycine receptors (GlyR) lateral dynamics in live cells. We discuss a study on the regulation of GlyR number at synapses by the cytoskeleton. We also investigate the interactions between GlyR and gephyrin (its scaffolding protein) in model cellular systems and we characterize the corresponding equilibrium.PARIS-BIUSJ-Thèses (751052125) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

L'effet du vieillissement sur la microcirculation cutanée

L'application d'une pression sur la peau provoque une vasodilatation cutanée, appelée vasodilatation induite par une pression (PIV), et retarde l'apparition de l'ischémie tissulaire liée à cette pression. La pression appliquée sur la peau active les fibres nerveuses capsaïno-sensibles, qui sécrètent en réponse des neurotransmetteurs, qui eux provoquent au niveau de l'endothélium la synthèse et la sécrétion de facteurs endothéliaux qui induisent une relaxation du muscle lisse. Ce travail avait pour objectif d'étudier l'effet du vieillissement sur la PIV. Chez la souris âgée, sans neuropathie périphérique, la PIV était altérée en raison d'une diminution de la vasodilatation endothélium-dépendante ; et la contribution des facteurs endothéliaux de la vasodilatation était modifiée : l'Endothelium-Derived Hyperpolarizing Factor jouait un rôle primordial en raison d'une diminution du monoxyde d'azote et de la prostacycline. Chez les sujets âgés (60-75 ans), la PIV était altérée en comparaison avec les sujets jeunes (20-35 ans) en raison d'une diminution de la vasodilatation endothélium-dépendante mais aussi d'une altération des fibres capsaïno-sensibles et/ou des neurotransmetteurs. En présence d'une neuropathie périphérique, la PIV était abolie. Ces modifications de la microcirculation cutanée au cours du vieillissement expliqueraient la plus grande vulnérabilité de la peau à l'ischémie et l'augmentation du risque d'ulcère de pression liée à l'âge. La compréhension des modifications de la PIV avec l'âge permet d'entrevoir de nouvelles perceptives de prévention et de traitement de l'ulcère de pression chez le sujet âgéThe pressure application on the skin leads to an increase of the cutaneous blood flow, called pressure-induced vasodilatation (PIV), that delays the occurrence of tissue ischemia resulting from this pressure. The development of this PIV depends on the activation by pressure of sensory C-fibres, leading to the release of neurotransmitters that acts at the endothelium level to stimulate the synthesis and release of endothelial factors inducing smooth muscle relaxation. This work had for objective to study the modifications of the PIV with the ageing. In old mice, without peripheral neuropathy, the PIV was reduced because of a decrease of the endothelium-dependent vasodilatation and the endothelium factors of the vasodilatation were redistributed with a contribution of Endothelium-Derived Hyperpolarizing Factor because of a decrease of the nitric oxide and the prostacyclin. In old subjects (60-75 years), the PIV was altered in comparison with young subjects (20-35 years) because of a decrease of the endothelium-dependent vasodilatation and a sensory fibres and/or neuromediators alteration. In the presence of a peripheral neuropathy, the PIV was abolished. These modifications of the cutaneous microcirculation with the ageing would lead to an early occurrence of ischemia related to an increased risk for pressure ulcers and the understanding of PIV modifications allow to glimpse of news perceptives of prevention and treatment of pressure ulcers in elderlyLYON1-BU.Sciences (692662101) / SudocSudocFranceF