Soins palliatifs et soins de support: à la frontière de la toute-puissance médicale [Palliative and supportive care: at the frontiers of medical omnipotence].

Cancer patients have physical, social, spiritual and emotional needs. They may suffer from severe physical symptoms, from social isolation, spiritual abandonment, and emotions such as sadness and anxiety, or feelings of deception, helplessness, anger and guilt. In some of them, the disease is rapidly progressing and ultimately they die. Their demanding care evokes intense feelings in health care providers, the more since these incurable patients represent a challenge, which could be condensed under the heading "the challenge of medical omnipotence". We suppose that the way health care providers cope with these circumstances has a profound influence on the way these patients are cared for. The attitudes towards the emerging heterogeneous movement of palliative and supportive care and towards its different models of implementation can be viewed from this point of view. We try to demonstrate these interrelations and to discuss the danger that may arise if they remain obscure and unreflected.

The effect of host plant and isolation on the genetic structure of phytophagous insects: A preliminary study on a bruchid beetle

Genetic differentiation is a consequence of the combination of drift and restriction in gene flow between populations due to barriers to dispersal, or selection against individuals resulting from inter-population matings In phytophagous insects, local adaptation to different kinds of host plants can sometimes lead to reproductive isolation and thus to genetic structuring, or even to speciation Acanthoscelides. obtectus Say is a bean bruchid specialized on beans of the Phaseolus vulgaris group, attacking both wild and domesticated forms of P vulgaris., and P coccineus This study reveals that the genetic structure of populations of this bruchid is explained mainly by their geographical location and is not related to a particular kind (wild or domesticated) of bean In contrast, the species of bean might have led, to some extent, to genetic structuring in these bruchids, although our sampling is too limited to address such process unambiguously. If confirmed, it would corroborate preliminary results found for the parasitoid species that attack Acanthoscelides species, which might show a genetic structure depending on the species of host plant

Genetic diversity and host plant preferences revealed by simple sequence repeat and mitochondrial markers in a population of the arbuscular mycorrhizal fungus Glomus intraradices.

Arbuscular mycorrhizal fungi (AMF) are important symbionts of plants that improve plant nutrient acquisition and promote plant diversity. Although within-species genetic differences among AMF have been shown to differentially affect plant growth, very little is actually known about the degree of genetic diversity in AMF populations. This is largely because of difficulties in isolation and cultivation of the fungi in a clean system allowing reliable genotyping to be performed. A population of the arbuscular mycorrhizal fungus Glomus intraradices growing in an in vitro cultivation system was studied using newly developed simple sequence repeat (SSR), nuclear gene intron and mitochondrial ribosomal gene intron markers. The markers revealed a strong differentiation at the nuclear and mitochondrial level among isolates. Genotypes were nonrandomly distributed among four plots showing genetic subdivisions in the field. Meanwhile, identical genotypes were found in geographically distant locations. AMF genotypes showed significant preferences to different host plant species (Glycine max, Helianthus annuus and Allium porrum) used before the fungal in vitro culture establishment. Host plants in a field could provide a heterogeneous environment favouring certain genotypes. Such preferences may partly explain within-population patterns of genetic diversity.

Gender difference in the response to an angiotensin-converting enzyme inhibitor and a diuretic in hypertensive patients of African descent.

BACKGROUND: The efficacy of angiotensin-converting enzyme (ACE) inhibitors in decreasing blood pressure in African patients is controversial. OBJECTIVE: We examined the ambulatory blood pressure (ABP) response to a diuretic and an ACE inhibitor in hypertensive patients of East African descent and evaluated the individual characteristics that determined treatment efficacy. DESIGN: A single-blind randomized AB/BA crossover design. SETTING: Hypertensive families of East African descent from the general population in the Seychelles. PARTICIPANTS: Fifty-two (29 men and 23 women) out of 62 eligible hypertensive patients were included.Main outcome measures ABP response to 20 mg lisinopril (LIS) daily and 25 mg hydrochlorothiazide (HCT) daily given for a 4-week period.Results The daytime systolic/diastolic ABP response to HCT was 4.9 [95% confidence interval (CI) 1.2-8.6]/3.6 (1.0-6.2) mmHg for men and 12.9 (9.2-16.6)/6.3 (3.7-8.8) mmHg for women. With LIS the response was 18.8 (15.0-22.5)/14.6 (12.0-17.1) mmHg for men and 12.4 (8.7-16.2)/7.7 (5.1-10.2) mmHg for women. The night-time systolic/diastolic response to HCT was 5.0 (0.6-9.4)/2.7 [(-0.4)-5.7] mmHg for men and 11.5 (7.1-16.0)/5.7 (2.6-8.8) mmHg for women, and to LIS was 18.7 (14.2-22.1)/15.4 (12.4-18.5) mmHg for men and 3.5 [(-1.0)-7.9]/2.3 [(-0.8)-5.4] mmHg for women. Linear regression analyses showed that gender is an independent predictor of the ABP responses to HCT and to LIS. CONCLUSIONS: Hypertensive patients of African descent responded better to LIS than to HCT. Men responded better to LIS than to HCT and women responded similarly to both drugs.

Tau hyperphosphorylation and increased BACE1 and RAGE levels in the cortex of PPARβ/δ-null mice.

The role of peroxisome proliferator activator receptor (PPAR)β/δ in the pathogenesis of Alzheimer's disease has only recently been explored through the use of PPARβ/δ agonists. Here we evaluated the effects of PPARβ/δ deficiency on the amyloidogenic pathway and tau hyperphosphorylation. PPARβ/δ-null mice showed cognitive impairment in the object recognition task, accompanied by enhanced DNA-binding activity of NF-κB in the cortex and increased expression of IL-6. In addition, two NF-κB-target genes involved in β-amyloid (Aβ) synthesis and deposition, the β site APP cleaving enzyme 1 (Bace1) and the receptor for advanced glycation endproducts (Rage), respectively, increased in PPARβ/δ-null mice compared to wild type animals. The protein levels of glial fibrillary acidic protein (GFAP) increased in the cortex of PPARβ/δ-null mice, which would suggest the presence of astrogliosis. Finally, tau hyperphosphorylation at Ser199 and enhanced levels of PHF-tau were associated with increased levels of the tau kinases CDK5 and phospho-ERK1/2 in the cortex of PPARβ/δ(-/-) mice. Collectively, our findings indicate that PPARβ/δ deficiency results in cognitive impairment associated with enhanced inflammation, astrogliosis and tau hyperphosphorylation in the cortex.

The effects of CYP2D6 and CYP3A activities on the pharmacokinetics of immediate release oxycodone

Background and purpose: There is high interindividual variability in the activity of drug-metabolizing enzymes catalysing the oxidation of oxycodone [cytochrome P450 (CYP) 2D6 and 3A], due to genetic polymorphisms and/or drug-drug interactions. The effects of CYP2D6 and/or CYP3A activity modulation on the pharmacokinetics of oxycodone remains poorly explored. Experimental approach: A randomized crossover double-blind placebo-controlled study was performed with 10 healthy volunteers genotyped for CYP2D6 [six extensive (EM), two deficient (PM/IM) and two ultrarapid metabolizers (UM)]. The volunteers randomly received on five different occasions: oxycodone 0.2 mg·kg−1 and placebo; oxycodone and quinidine (CYP2D6 inhibitor); oxycodone and ketoconazole (CYP3A inhibitor); oxycodone and quinidine+ketoconazole; placebo. Blood samples for plasma concentrations of oxycodone and metabolites (oxymorphone, noroxycodone and noroxymorphone) were collected for 24 h after dosing. Phenotyping for CYP2D6 (with dextromethorphan) and CYP3A (with midazolam) were assessed at each session. Key results: CYP2D6 activity was correlated with oxymorphone and noroxymorphone AUCs and Cmax (−0.71 < Spearman correlation coefficient ρs < −0.92). Oxymorphone Cmax was 62% and 75% lower in PM than EM and UM. Noroxymorphone Cmax reduction was even more pronounced (90%). In UM, oxymorphone and noroxymorphone concentrations increased whereas noroxycodone exposure was halved. Blocking CYP2D6 (with quinidine) reduced oxymorphone and noroxymorphone Cmax by 40% and 80%, and increased noroxycodone AUC∞ by 70%. Blocking CYP3A4 (with ketoconazole) tripled oxymorphone AUC∞ and reduced noroxycodone and noroxymorphone AUCs by 80%. Shunting to CYP2D6 pathway was observed after CYP3A4 inhibition. Conclusions and implications: Drug-drug interactions via CYP2D6 and CYP3A affected oxycodone pharmacokinetics and its magnitude depended on CYP2D6 genotype.

Continuity and change in the gender segregation of the medical profession in Britain and France

It is a well established fact that the entry of women into higher-level professional occupations has not resulted in their equal distribution within these occupations. Indeed, the emergence and persistence of horizontal and vertical gender segregation within the professions has been at the heart of the development of a range of alternative theoretical perspectives on both the "feminisation process" and the future of the "professions"more generally. Through an in-depth comparative analysis of the recent changes in the organisation and administration of the medical profession in Britain and France, this paper draws upon statistical data and biographical interviews with male and female general practitioners (GPs) in both countries in order to discuss and review a variety of approaches that have been adopted to explain and analyse the "eminisation" process of higher-level professions. Our conclusions review the theoretical debates in the light of the evidence we have presented. It is argued that, despite important elements of continuity in respect of gendered occupational structuring in both countries, national variations in both professional and domestic gendered architectures lead to different outcomes as far as the extent and patterns of internal occupational segregation are concerned. Both female and male doctors are currently seeking - with some effect - to resist thepressures of medicine on family life.

Ex-post survey on the consequences and perceptions about amalgamation : The case of two Swiss municipalities

In 2006, two municipalities located in the canton of Fribourg (Switzerland), La Tour-de-Trême and Bulle, amalgamated. In this study, we report on the evolution of citizen perceptions as well as try to better understand the reasons behind the respondents various positions concerning this new political and territorial entity. Five-hundred individuals were surveyed almost four years after the amalgamation came into effect. Our results show that if the amalgamation was voted again, it would be necessary to be particularly attentive to citizen access to municipal offices and to local service provisions, to citizen identification to their municipality as well as to the life of the local associations. Indeed, these are clearly important issues for small localities. Furthermore, citizens of the newly amalgamated municipality are mostly sensitive to access to municipal offices and to contact with local representatives. Improving the population's perceptions of these particular issues could lead to a 12 percentage point increase in support for the amalgamation.

Appropriate therapy for fistulizing and fibrostenotic Crohn's disease: results of a multidisciplinary expert panel - EPACT II

Introduction: Many therapeutic decisions in the management of fistulizing and fibrostenotic Crohn's disease (CD) have to be taken without the benefit of strong scientific evidence. For this reason, explicit appropriateness criteria for CD fistula and stenosis treatment were developed by a multidisciplinary European expert panel in 2004 with the aim of making them easily available on the Internet and thus allowing individual case scenario evaluation; these criteria were updated in 2007. Methods: Twelve international experts convened in Geneva, Switzerland in December 2007. Explicit clinical scenarios, corresponding to real daily practice, were rated on a 9-point scale based on evidence from the published literature and panelists' own expertise. Median ratings were stratified into three categories: appropriate (7-9), uncertain (4-6) and inappropriate (1-3). Results: Overall, panelists rated 60 indications pertaining to fistulas. Antibiotics, azathioprine/6-mercaptopurine and conservative surgery are the mainstay of therapy for simple and complex fistulas. In the event of previous failure of azathioprine/6-mercaptopurine therapy, methotrexate and infliximab were considered appropriate for complex fistulas. The panel also rated 72 indications related to the management of fibrostenotic CD. The experts considered balloon dilation, if the stricture was endoscopically accessible, stricturoplasty and bowel resection to be appropriate for small bowel fibrostenotic Crohn's disease, and balloon dilation and bowel resection appropriate for fibrostenotic colonic disease. In the presence of an ileocolonic or ileorectal anastomotic stricture of <7 cm, endoscopic balloon dilation, and bowel resection were considered appropriate. Conclusion: Antibiotics, azathioprine/6-mercaptopurine, and conservative surgery are the mainstay of therapy for fistulizing Crohn's disease. Infliximab is a therapeutic option in patients without prior response to immunosuppressant therapy. In fibrostenotic Crohn's disease, endoscopic balloon dilation, if feasible, or surgical therapy should be considered. These expert recommendations are available online (www.epact.ch). Prospective evaluation is now needed to test the validity of these appropriateness criteria in clinical practice. (C) 2009 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Segmentation and grid generation for numerical simulations of vad connections with patient-specific data

Objectives: We are interested in the numerical simulation of the anastomotic region comprised between outflow canula of LVAD and the aorta. Segmenta¬tion, geometry reconstruction and grid generation from patient-specific data remain an issue because of the variable quality of DICOM images, in particular CT-scan (e.g. metallic noise of the device, non-aortic contrast phase). We pro¬pose a general framework to overcome this problem and create suitable grids for numerical simulations.Methods: Preliminary treatment of images is performed by reducing the level window and enhancing the contrast of the greyscale image using contrast-limited adaptive histogram equalization. A gradient anisotropic diffusion filter is applied to reduce the noise. Then, watershed segmentation algorithms and mathematical morphology filters allow reconstructing the patient geometry. This is done using the InsightToolKit library (www.itk.org). Finally the Vascular Model¬ing ToolKit (www.vmtk.org) and gmsh (www.geuz.org/gmsh) are used to create the meshes for the fluid (blood) and structure (arterial wall, outflow canula) and to a priori identify the boundary layers. The method is tested on five different patients with left ventricular assistance and who underwent a CT-scan exam.Results: This method produced good results in four patients. The anastomosis area is recovered and the generated grids are suitable for numerical simulations. In one patient the method failed to produce a good segmentation because of the small dimension of the aortic arch with respect to the image resolution.Conclusions: The described framework allows the use of data that could not be otherwise segmented by standard automatic segmentation tools. In particular the computational grids that have been generated are suitable for simulations that take into account fluid-structure interactions. Finally the presented method features a good reproducibility and fast application.

From Translation to Rewriting : the Interplay of Text and Image in The Fairy Tales of Charles Perrault and The Bloody Chamber and Other Stories

Abstract :This article examines the interplay of text and image in The Fairy Tales of Charles Perrault (1977), translated by Angela Carter and illustrated by Martin Ware, as a form of intersemiotic dialogue that sheds new light on Carter's work. It argues that Ware's highly original artwork based on the translation not only calls into question the association of fairy tales with children's literature (which still characterizes Carter's translation), but also captures an essential if heretofore neglected aspect of Carter's creative process, namely the dynamics between translating, illustrating and rewriting classic tales. Several elements from Ware's illustrations are indeed taken up and elaborated on in The Bloody Chamber and Other Stories (1979), the collection of "stories about fairy stories" that made Carter famous. These include visual details and strategies that she transposed to the realm of writing, giving rise to reflections on the relation between visuality and textuality.RésuméCet article considère l'interaction du texte et de l'image dans les contes de Perrault traduits par Angela Carter et illustrés par Martin Ware (The Fairy Tales of Charles Perrault, 1977) comme une forme de dialogue intersémiotique particulièrement productif. Il démontre que les illustrations originales de Ware ne mettent pas seulement en question l'assimilation des contes à la littérature de jeunesse (qui est encore la perspective adoptée par la traductrice dans ce livre), mais permettent aussi de saisir un aspect essentiel bien que jusque là ignoré du procession de création dans l'oeuvre de Carter, à savoir la dynamique qui lie la traduction, l'illustration et la réécriture des contes classiques. Plusieurs éléments des illustrations de Ware sont ainsi repris et élaborés dans The Bloody Chamber and Other Stories (1979), la collection de "stories about fairy stories" qui rendit Carter célèbre. La transposition de détails et de stratégies visuelles dans l'écriture donnent ainsi l'occasion de réflexions sur les rapports entre la visualité et la textualité.

Association of alcohol consumption and HIV surrogate markers in participants of the swiss HIV cohort study.

BACKGROUND: Alcohol consumption may affect the course of HIV infection and/or antiretroviral therapy (ART). The authors investigated the association between self-reported alcohol consumption and HIV surrogate markers in both treated and untreated individuals. DESIGN: Prospective cohort study. METHODS: Over a 7-year period, the authors analyzed 2 groups of individuals in the Swiss HIV Cohort Study: (1) ART-naïve individuals remaining off ART and (2) individuals initiating first ART. For individuals initiating first ART, time-dependent Cox proportional hazards models were used to assess the association between alcohol consumption, virological failure, and ART interruption. For both groups, trajectories of log-transformed CD4 cell counts were analyzed using linear mixed models with repeated measures. RESULTS: The authors included 2982 individuals initiating first ART and 2085 ART naives. In individuals initiating first ART, 241 (8%) experienced virological failure. Alcohol consumption was not associated with virological failure. ART interruption was noted in 449 (15%) individuals and was more prevalent in severe compared with none/light health risk drinkers [hazard ratio: 2.24, 95% confidence interval: 1.42 to 3.52]. The association remained significant even after adjusting for nonadherence. The authors did not find an association between alcohol consumption and change in CD4 cell count over time in either group. CONCLUSIONS: No effect of alcohol consumption on either virological failure or CD4 cell count in both groups of ART-initiating and ART-naive individuals was found. However, severe drinkers were more likely to interrupt ART. Efforts on ART continuation should be especially implemented in individuals reporting high alcohol consumption.