Transcatheter aortic valve implantation (TAVI): state of the art techniques and future perspectives.

Transcatheter aortic valve therapies are the newest established techniques for the treatment of high risk patients affected by severe symptomatic aortic valve stenosis. The transapical approach requires a left anterolateral mini-thoracotomy, whereas the transfemoral method requires an adequate peripheral vascular access and can be performed fully percutaneously. Alternatively, the trans-subclavian access has been recently proposed as a third promising approach. Depending on the technique, the fine stent-valve positioning can be performed with or without contrast injections. The transapical echo-guided stent-valve implantation without angiography (the Lausanne technique) relies entirely on transoesophageal echocardiogramme imaging for the fine stent-valve positioning and it has been proved that this technique prevents the onset of postoperative contrast-related acute kidney failure. Recent published reports have shown good hospital outcomes and short-term results after transcatheter aortic valve implantation, but there are no proven advantages in using the transfemoral or the transapical technique. In particular, the transapical series have a higher mean logistic Euroscore of 27-35%, a procedural success rate above 95% and a mean 30-day mortality between 7.5 and 17.5%, whereas the transfemoral results show a lower logistic Euroscore of 23-25.5%, a procedural success rate above 90% and a 30-day mortality of 7-10.8%. Nevertheless, further clinical trials and long-term results are mandatory to confirm this positive trend. Future perspectives in transcatheter aortic valve therapies would be the development of intravascular devices for the ablation of the diseased valve leaflets and the launch of new stent-valves with improved haemodynamic, different sizes and smaller delivery systems.

Maladie d'Alzheimer: de la pathogénie aux perspectives cliniques [Alzheimer disease: from pathogenetic issues to clinical perspectives].

The aim of this article is a critical review of the main pathogenetic issues debated in Alzheimer disease, with a focus on the clinical perspectives that could derive from. The pertinence of the amyloid cascade hypothesis as a unique and causal explanation of cognitive deterioration is challenged in the light of recent therapeutic failures of clinical trials and increasing role of tau protein in clinical expression. The detection of very early and possibly preclinical stages of the disease emerges as a necessary condition for the efficacy of future amyloid or tau-oriented curative strategies. In this respect, the possibility of finding individual vulnerability markers--in the group of patients with "mild cognitive impairment" or even in cognitively intact subjects--represents a major challenge of the clinical research in this field.

Ganglion sentinelle dans les cancers du col de faible stade. Données actuelles. Assurance qualité. Perspectives [Sentinel lymph node in low stage cervical cancers. Current data. Quality assurance. Prospects].

Le prélèvement des ganglions sentinelles apparaît comme une technique séduisante pour l'évaluation ganglionnaire des cancers du col utérin de faible stade. La sélection d'une population à bas risque de métastase ganglionnaire, un entraînement minimal et le respect de quelques règles simples permettent de limiter le risque de faux négatif au minimum. La technique apporte des informations supplémentaires sur le plan anatomique en identifiant des ganglions situés en dehors des zones habituelles de curage, et sur le plan histologique avec la mise en évidence de cellules tumorales isolées et surtout de micrométastases dont la valeur pronostique est suspectée Sentinel node biopsy appears as a promising technique for the assessment of nodal disease in early cervical cancers. Selection of a population with a low risk of nodal metastasis, a minimal training, and simple rules allow a low false negative rate. Sentinel node biopsy provides supplementary information, such as anatomical information (nodes outside of routine lymphadenectomy areas) and histological information (isolated tumors cells and micrometastases).

The role of proteolytic processing and the stable signal peptide in expression of the Old World arenavirus envelope glycoprotein ectodomain.

Maturation of the arenavirus GP precursor (GPC) involves proteolytic processing by cellular signal peptidase and the proprotein convertase subtilisin kexin isozyme 1 (SKI-1)/site 1 protease (S1P), yielding a tripartite complex comprised of a stable signal peptide (SSP), the receptor-binding GP1, and the fusion-active transmembrane GP2. Here we investigated the roles of SKI-1/S1P processing and SSP in the biosynthesis of the recombinant GP ectodomains of lymphocytic choriomeningitis virus (LCMV) and Lassa virus (LASV). When expressed in mammalian cells, the LCMV and LASV GP ectodomains underwent processing by SKI-1/S1P, followed by dissociation of GP1 from GP2. The GP2 ectodomain spontaneously formed trimers as revealed by chemical cross-linking. The endogenous SSP, known to be crucial for maturation and transport of full-length arenavirus GPC was dispensable for processing and secretion of the soluble GP ectodomain, suggesting a specific role of SSP in the stable prefusion conformation and transport of full-length GPC.

Male beach workers and western female tourists : livelihood strategies in Kenya's south coast region

Recent years have seen an emerging knowledge base and increasing public interest and awareness of sexual-economic relationships between local men and Western women, in different touristic regions around the world. However, to date, Western perspectives on the phenomenon make up the bulk of the existent literature. Questioning the dominant discourse of 'romance tourism' and representations of male participants as 'victims-opportunists', this dissertation explores male beach workers' experiences with, and perspectives on sexual-economic relationships between Kenyan men and visiting Western women in Kenya's South Coast region. The men were not considered in isolation; their experiences and perspectives are situated in relation to their family ties, social networks and the political economy of beach tourism. The study shows that locally these relationships are clearly understood as livelihood strategies for the visited. Men seek to establish long-term intimate relationships with female tourists as a means to accessing life's basic necessities for themselves and for their families and overall to improve their standards of living. It is argued that these relationships are a response to the poverty and inequalities generated by socio-economic changes over time. They are also a response to local gender role prescriptions that hinge male social value on men's capacity to marry, procreate and provide intergenerational social and economic support. The men's parallel quest for non-sexual economically motivated friendships with visiting foreign tourists termed "family friends" is a salient finding, that serves to reinforce the finding that the sexual- economic relationships are above all livelihood strategies. Résumé Ces dernières années ont vu l'émergence d'une base de connaissance, ainsi que d'un intérêt et d'une prise de conscience accrue du public, à l'égard des relations économico-sexuelles entre hommes locaux et femmes occidentales, dans différentes régions touristiques du monde. Cependant, à ce jour, des perspectives occidentales sur ce phénomène constituent l'essentiel de la littérature existante. En remettant en question le discours dominant du «romance tourism» (tourisme sentimental) et les représentations qui conçoivent les hommes participants comme étant 'victimes-opportunistes', cette thèse explore les expériences, et les visions qu'ont les travailleurs de plage sur les relations économico-sexuelles entre hommes Kenyans et femmes Occidentales dans la région de la côte sud du Kenya. Les hommes n'ont pas été considérés de manière isolée; leurs expériences et leurs perspectives sont situées par rapport à leur liens familiaux, leur réseaux sociaux et aussi par rapport à l'économie politique du tourisme balnéaire. L'étude montre que sur place ces relations sont clairement conçues comme des stratégies de survie pour les participants hôtes. Les hommes cherchent à établir des relations de long durée avec des femmes touristes comme moyen d'accéder à des biens et des services qui constituent des nécessités de bases, pour eux et pour leur familles et globalement pour relever leur niveau de vie! L'étude fait valoir que ces relations sont une réponse à la pauvreté et aux inégalités sociales crées par des dynamiques socio-économiques au fil du temps. Elles sont aussi une réponse au prescriptions sociales locales par lesquelles la valeur sociale masculine est définie à travers la capacité des hommes à se marier, à procréer et d'assurer un soutien intergénérationnel social et économique. La quête, en parallèle, de relations d'amitiés non-sexuelles à motivation économique, dénommé « family friends », par des hommes, est un résultat saillant de cette étude qui vient renforcer l'observation que les relations économico-sexuelles relèvent avant tout des stratégies de survie.

Rabies postexposure prophylaxis in routine practice in view of the new centers for disease control and prevention and world health organization recommendations.

Background. New recommendations for rabies postexposure prophylaxis (PEP) were published by the Centers for Disease Control and Prevention and the World Health Organization in 2010. In view of these new recommendations, we investigated the adequacy of rabies PEP among patients consulting our travel clinic. Methods. A retrospective analysis of the files of all patients who consulted for rabies PEP at the Travel Clinic of the University Hospital in Lausanne, Switzerland, between January 2005 and August 2011 was conducted. Results. A total of 110 patients who received rabies PEP were identified. The median age of the patients was 34 years (range, 2-79 years), and 53% were women. Ninety subjects were potentially exposed to rabies while travelling abroad. Shortcomings in the management of these patients were (1) late initiation of rabies PEP in travelers who waited to seek medical care until returning to Switzerland, (2) administration of human rabies immunoglobulin (HRIG) to only 7 of 50 travelers (14%) who sought care abroad and for whom HRIG was indicated, and (3) antibody levels <0.5 IU/mL in 6 of 90 patients (6.7%) after 4 doses of vaccine. Conclusions. Patients do not always receive optimal rabies PEP under real-life conditions. A significant proportion of patients did not develop adequate antibody levels after 4 doses of vaccine. These data indicate that the measurement of antibody levels on day 21 of the Essen PEP regimen is useful in order to verify an adequate immune response.

Cannabis and benzodiazepines as determinants of methadone trough plasma concentration variability in maintenance treatment: a transnational study.

PURPOSE: To assess tobacco, alcohol, cannabis and benzodiazepine use in methadone maintenance treatment (MMT) as potential sources of variability in methadone pharmacokinetics. METHODS: Trough plasma (R)- and (S)-methadone concentrations were measured on 77 Australian and 74 Swiss MMT patients with no additional medications other than benzodiazepines. Simple and multiple regression analyses were performed for the primary metric, plasma methadone concentration/dose. RESULTS: Cannabis and methadone dose were significantly associated with lower 24-h plasma (R)- and (S)-methadone concentrations/dose. The models containing these variables explained 14-16% and 17-25% of the variation in (R)- and (S)-methadone concentration/dose, respectively. Analysis of 61 patients using only CYP3A4 metabolised benzodiazepines showed this class to be associated with higher (R)-concentration/dose, which is consistent with a potential competitive inhibition of CYP3A4. CONCLUSION: Cannabis use and higher methadone doses in MMT could in part be a response to-or a cause of-more rapid methadone clearance. The effects of cannabis and benzodiazepines should be controlled for in future studies on methadone pharmacokinetics in MMT.

Analytical aspects in doping control: challenges and perspectives.

Since the first anti-doping tests in the 1960s, the analytical aspects of the testing remain challenging. The evolution of the analytical process in doping control is discussed in this paper with a particular emphasis on separation techniques, such as gas chromatography and liquid chromatography. These approaches are improving in parallel with the requirements of increasing sensitivity and selectivity for detecting prohibited substances in biological samples from athletes. Moreover, fast analyses are mandatory to deal with the growing number of doping control samples and the short response time required during particular sport events. Recent developments in mass spectrometry and the expansion of accurate mass determination has improved anti-doping strategies with the possibility of using elemental composition and isotope patterns for structural identification. These techniques must be able to distinguish equivocally between negative and suspicious samples with no false-negative or false-positive results. Therefore, high degree of reliability must be reached for the identification of major metabolites corresponding to suspected analytes. Along with current trends in pharmaceutical industry the analysis of proteins and peptides remains an important issue in doping control. Sophisticated analytical tools are still mandatory to improve their distinction from endogenous analogs. Finally, indirect approaches will be discussed in the context of anti-doping, in which recent advances are aimed to examine the biological response of a doping agent in a holistic way.