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L'on étudie la remise en suspension de microparticules isolées, déposées en monocouche et soumises à des accélérations d'air suivies de régime permanent. Différents profils temporels de vitesses sont appliqués dans une gaine de ventilation, et le suivi eulérien des particules résolu dans le temps est réalisé. Les données sont traitées à l'aide d'un algorithme de détection de particules. En parallèle, la vitesse de l'écoulement au centre de la veine et la vitesse de frottement à la paroi sont enregistrées par anémométrie à fil et film chaud. Nous mettons en exergue l'influence du régime transitoire dans le phénomène de remise en suspension, puis réalisons des analyses dimensionnelles permettant de prendre en compte les caractéristiques de l'écoulement dans la remise en suspension., The resuspension of microparticles deposited as a monolayer of isolated particles and subjected to airflow acceleration followed by steady-state is studied. Different temporal velocity profiles are applied in a ventilation duct, and the time-resolved Eulerian tracking of the particles is monitored. Data are then processed using a particle detection algorithm. In parallel, the flow velocity at the centre of the channel and the friction velocity at the wall are recorded by hot wire and hot film anemometry. We highlight the influence of the transient regime in the resuspension phenomenon, and then carry out dimensional analyses to take into account the characteristics of the flow in the resuspension.

International audience; Data assimilation consists in combining a model and measurements in order to estimate the state of the system. In wind engineering, the interest to take advantage of both sources of information is extremely high. As a matter of fact, on the one hand, measurements in wind tunnel experiments are in practice extremely sparse and, on the other hand, stationary numerical models based on Reynolds averaged Navier-Stokes (RANS) fail to predict the time-averaged wake accurately. Variational data assimilation (VDA) techniques are defined as high-dimensional optimisation problems, the solution of which is determined through an adjoint method. In practical applications, where only wall pressure measurements on the building are available, an accurate mean flow reconstruction is very challenging, especially in regions far away from any measurements. In the present paper, spatially distributed forces are considered as a control parameter on the momentum equation or the turbulence closure equations. These forcings are interpreted as corrections brought to the turbulence closure. Consequently, the problem corresponds to a high-dimensional optimisation problem for a spatially distributed variable with sparse pressure measurements. Some guidelines are brought here to perform accurate and physically consistent reconstructions for wind engineering applications. In order to deal as closely as possible with a practical application, this study focuses on the realizable revision of the k − ϵ RANS model applied on a high-rise building wake flow. In particular, some regularisation strategies as well as efficient techniques for control parameter selection and identification are provided. 1

L'on s'intéresse à la remise en suspension de microparticules isolées déposées en monocouche sur une paroi d'un système de ventilation. Ces particules sont soumises à des accélérations d'air et le comportement des dépôts est enregistré par méthodes optiques. Les résultats sont analysés à l'aide d'un nouvel algorithme de traitement d'images ; cet algorithme retourne la cinétique de remise en suspension - l'évolution du nombre de particules remises en suspension ou restant à la paroi en fonction du temps - et permet de catégoriser les particules suivant leur taille, ainsi que les agglomérats de particules présents sur le dépôt., The focus is on resuspension of isolated microparticles deposited in a monolayer on a wall. These particles are subject to air flow acceleration and the deposit behaviour is monitored by optical method. Results are analysed using a new image processing algorithm; this algorithm returns the resuspension kinetics - the particle number evolution with respect to time - and allows for the categorisation of particles in terms of size, as well as particle clusters in the deposit.

The invasion of tumor cells from the primary tumor is mediated by invadopodia, actin-rich protrusive organelles that secrete matrix metalloproteases and degrade the extracellular matrix. This coupling between protrusive activity and matrix degradation facilitates tumor invasion. We previously reported that the PI3Kβ isoform of PI 3-kinase, which is regulated by both receptor tyrosine kinases and G protein–coupled receptors, is required for invasion and gelatin degradation in breast cancer cells. We have now defined the mechanism by which PI3Kβ regulates invadopodia. We find that PI3Kβ is specifically activated downstream from integrins, and is required for integrin-stimulated spreading and haptotaxis as well as integrin-stimulated invadopodia formation. Surprisingly, these integrin-stimulated and PI3Kβ-dependent responses require the production of PI(3,4)P2 by the phosphoinositide 5′-phosphatase SHIP2. Thus, integrin activation of PI3Kβ is coupled to the SHIP2-dependent production of PI(3,4)P2, which regulates the recruitment of PH domain-containing scaffolds such as lamellipodin to invadopodia. These findings provide novel mechanistic insight into the role of PI3Kβ in the regulation of invadopodia in breast cancer cells.

Phosphoinositide 3-kinase β (PI3Kβ) is regulated by receptor tyrosine kinases (RTKs), G protein–coupled receptors (GPCRs), and small GTPases such as Rac1 and Rab5. Our lab previously identified two residues (Gln(596) and Ile(597)) in the helical domain of the catalytic subunit (p110β) of PI3Kβ whose mutation disrupts binding to Rab5. To better define the Rab5–p110β interface, we performed alanine-scanning mutagenesis and analyzed Rab5 binding with an in vitro pulldown assay with GST-Rab5(GTP). Of the 35 p110β helical domain mutants assayed, 11 disrupted binding to Rab5 without affecting Rac1 binding, basal lipid kinase activity, or Gβγ-stimulated kinase activity. These mutants defined the Rab5-binding interface within p110β as consisting of two perpendicular α-helices in the helical domain that are adjacent to the initially identified Gln(596) and Ile(597) residues. Analysis of the Rab5–PI3Kβ interaction by hydrogen-deuterium exchange MS identified p110β peptides that overlap with these helices; no interactions were detected between Rab5 and other regions of p110β or p85α. Similarly, the binding of Rab5 to isolated p85α could not be detected, and mutations in the Ras-binding domain (RBD) of p110β had no effect on Rab5 binding. Whereas soluble Rab5 did not affect PI3Kβ activity in vitro, the interaction of these two proteins was critical for chemotaxis, invasion, and gelatin degradation by breast cancer cells. Our results define a single, discrete Rab5-binding site in the p110β helical domain, which may be useful for generating inhibitors to better define the physiological role of Rab5–PI3Kβ coupling in vivo.

Macropinocytosis is an actin-dependent but clathrin-independent endocytic process by which cells nonselectively take up large aliquots of extracellular material. Macropinocytosis is used for immune surveillance by dendritic cells, as a route of infection by viruses and protozoa, and as a nutrient uptake pathway in tumor cells. In this study, we explore the role of class I phosphoinositide 3-kinases (PI3Ks) during ligand-stimulated macropinocytosis. We find that macropinocytosis in response to receptor tyrosine kinase activation is strikingly dependent on a single class I PI3K isoform, namely PI3Kβ (containing the p110β catalytic subunit encoded by PIK3CB). Loss of PI3Kβ expression or activity blocks macropinocytosis at early steps, before the formation of circular dorsal ruffles, but also plays a role in later steps, downstream from Rac1 activation. PI3Kβ is also required for the elevated levels of constitutive macropinocytosis found in tumor cells that are defective for the PTEN tumor suppressor. Our data shed new light on PI3K signaling during macropinocytosis, and suggest new therapeutic uses for pharmacological inhibitors of PI3Kβ.

Introduction Determiner les criteres pertinents a prendre en compte pour inscrire un patient de plus de 70 ans sur liste d’attente de transplantation renale est un probleme croissant dans la vie quotidienne du nephrologue. L’extrapolation des resultats de la litterature est difficile a l’echelle individuelle. Une evaluation geriatrique pourrait apporter de nouveaux criteres d’evaluation pre-transplantation utiles a la decision. Description Cent douze patients âges de 70 ans ou plus, adresses pour une evaluation pre-transplantation, ont ete inclus dans notre etude observationnelle monocentrique. Une evaluation geriatrique complete a ete realisee pour tous les patients. Les conclusions des geriatres et des nephrologues ont ete comparees. Les patients transplantes ont ete suivis. Methode Les parametres pre-transplantation associes a la duree d’hospitalisation initiale et a la duree totale d’hospitalisation pendant la premiere annee post-transplantation ont ete recherches en analyses uni- et multivariee, avec courbes ROC pour les parametres identifies. Resultats Cent patients ont termine l’evaluation pre-transplantation. Soixante-huit patients (68 %) ont ete inscrits sur liste d’attente. Les avis des geriatres et des nephrologues etaient similaires pour 74 patients (74 %). Les divergences etaient dues a des appreciations differentes entre geriatres et nephrologues. A la fin de l’etude, 22 patients inscrits (32 %) ont ete transplantes et 13 patients (11,6 %) sont decedes. La duree d’hospitalisation initiale etait associee a la SPPB (Short Physical Performance Battery) et a un score pronostique de survie en dialyse. La duree totale d’hospitalisation etait associee a l’âge et a un score de comorbidites. Conclusion L’acces a la transplantation dans cette population reste mediocre. L’expertise des geriatres apporte de precieuses informations dans l’evaluation pre-transplantation des personnes âgees. Nous avons identifie plusieurs scores geriatriques pertinents pour l’evaluation pre-transplantation. Ceux-ci pourraient permettre une meilleure objectivite et aider les nephrologues a selectionner plus objectivement les patients âges.

Background: Ovarian germ cell tumors (OGCT) are rare gynecological neoplasms, mostly affecting children and young women. The underlying molecular genetic background of these tumors is poorly characterized. Methods: We analyzed somatic copy number aberration (CNA) profiles in 87 OGCT tumors and performed whole exome sequencing (WES) on 24 OGCT tumor and matched germline samples to further elucidate their molecular genetic landscape. Results: The overall mutation rate was very low in OGCT compared to other human cancers, with an average of 0.05 mutations per Mb, consistent with their embryological origin. We identified recurrent mutations in KIT and KRAS, while CNA profiling revealed frequent focal amplifications affecting PIK3CA and AKT1 in yolk sac tumors, recurrent focal deletions affecting chromosomal regions 1p36.32, 2q11.1, 4q28.1, 5p15.33, 5q11.1 and 6q27, as well as gains in chromosome 12p that were present in all tumors, except for pure immature teratomas. Conclusion: We here present the first whole exome sequencing data and to our knowledge the largest CNA study in OGCT. We confirmed that earlier reported KIT mutations were frequent in dysgerminomas and mixed forms with a dysgerminoma component, whereas chromosome 12p gains were present in all histological subtypes except pure immature teratomas. We detected recurrent KRAS mutations, recurrent focal deletions and an enrichment in the PI3K/AKT/PTEN pathway in yolk sac tumors. Several of these aberrations involve targetable pathways, offering novel treatment modalities for OGCT. © 2018

El cancer de endometrio es el cancer ginecologico pelvico mas frecuente en Francia, con 6.800 casos anuales. En la mayoria de las ocasiones, se produce despues de la menopausia y, por lo general, se diagnostica en un estadio precoz debido a una semiologia muy llamativa: las metrorragias posmenopausicas, por lo que es un cancer de buen pronostico. Los principales factores de riesgo son la obesidad, la diabetes y la exposicion prolongada a los estrogenos. Existen formas de cancer de endometrio que aparecen en pacientes mas jovenes y que requieren la busqueda de un sindrome de cancer colorrectal no poliposico hereditario (sindrome de Lynch). Se han definido dos tipos histologicos de canceres del endometrio: el tipo 1 (tumores endometrioides) y el tipo 2 (que incluye los carcinomas de celulas claras, los carcinomas papilares serosos y los carcinosarcomas). Su tratamiento y su pronostico difieren, tal y como se recoge en las nuevas recomendaciones del Institut National du Cancer frances de 2010. El reto terapeutico consiste en no tratar en exceso las formas de buen pronostico, para reducir la morbilidad, pero sin subtratar las formas de pronostico menos bueno. Cualquier metrorragia posmenopausica debe evaluarse mediante un frotis cervicovaginal, una ecografia pelvica y una biopsia del endometrio. El estudio preterapeutico de un cancer diagnosticado consiste en la realizacion sistematica de una resonancia magnetica abdominopelvica con apreciacion del grado de infiltracion del miometrio y exploracion de las areas ganglionares. El tratamiento consiste en cirugia (salvo en los estadios tardios), dando prioridad a la via laparoscopica, y en radioterapia externa. La realizacion de linfadenectomias no es sistematica, sobre todo en los tumores limitados al cuerpo uterino con bajo riesgo de recidiva. El seguimiento se basa exclusivamente en la clinica.

PURPOSE: Breast cancer is the most common malignancy in women in terms of incidence and mortality. Age is undoubtedly the biggest breast cancer risk factor. In this study we examined clinical, histological, and biological characteristics and mortality of breast cancer in elderly women along with their changes with advancing age. METHODS: We reviewed 63 original articles published between 2006 and 2016 concerning women over 70 years with breast cancer. RESULTS: Compared to patients 70-79 years, patients aged 80 and over had larger tumor size with fewer T1 (42.9% vs 57.7%, p < 0.01) and more T2 lesions (43.5% vs 33.0%, p < 0.01). Lymph nodes and distant metastases were more frequent, with more N + (49.5% vs 44.0%, p < 0.01) and more M1 (8.0% vs 5.9%, p < 0.01). Infiltrating mucinous carcinomas were more frequent (4.3% vs 3.7%, p < 0.01). Tumors had lower grades, with more grade 1 (23.2% vs 19.8%, p = 0.01) and fewer grade 3 (21.5% vs 25.5%, p < 0.01), and were more hormone-sensitive: PR was more often expressed (72.6% vs 67.3%, p < 0.01). Lympho-vascular invasion was less frequent in the 80 years and over (22.9% vs 29.7%, p = 0.01). Breast cancer-specific mortality was higher both at 5 years (25.8% vs 17.2%, p < 0.01) and 10 years (32.7% vs 26.6%, p < 0.01). CONCLUSION: Clinico-pathological characteristics, increased incidence, and mortality associated with aging can be explained on one hand by biological changes of the breast such as increased estrogen sensitivity, epithelial cell alterations, immune senescence, and tumor microenvironment modifications. However, sociologic factors such as increased life expectancy, under-treatment, late diagnosis, and insufficient individual screening, are also involved.

Resume Objectifs La participation des femmes au depistage organise du cancer du sein etait de 52 % en France et de 40 % en Ile de France en 2010. Nous avons voulu etudier les causes de non-participation au depistage organise et les reticences des femmes a celui-ci a l’echelle d’un departement francilien. Materiel et methodes Un questionnaire anonyme a ete adresse aux non repondantes au depistage organise du cancer du sein dans les Yvelines en Septembre 2011 a l’occasion de l’evenement « Octobre Rose », mois de la mobilisation nationale pour le depistage organise du cancer du sein. L’analyse de ces questionnaires a permis de determiner les causes de non-adhesion au depistage organise et les reticences au depistage. Nous avons compare chez les repondantes au questionnaire les caracteristiques des patientes ayant un depistage individuel a celles des patientes n’ayant aucun depistage. Resultats Vingt-neuf mille neuf-cent quatre-vingt-douze questionnaires ont ete adresses et 3026 reponses recues (10 %). Deux mille six cent quinze femmes (86 %) declaraient un suivi regulier et realiser des mammographies tous les deux ans alors que 411 (14 %) declaraient un suivi occasionnel ou inexistant. Concernant les reticences a realiser l’examen, le manque de temps, le mauvais souvenir d’un examen precedent et la peur de la douleur etaient les freins preponderants. Pres de 50 % des femmes ne participaient pas au depistage car elles ne s’estimaient pas a risque pour diverses raisons (absence de symptomes, bonne hygiene de vie ou absence d’antecedents familiaux) et 22 % des femmes interrogees avaient une attitude de deni face a la maladie. Le profil type de femmes ne realisant ni depistage organise ni depistage individuel du cancer du sein etait celui de femmes de moins de 60 ans, celibataires, en activite, de categorie socioprofessionnelle basse et consultant peu leur medecin traitant ou leur gynecologue. Les professionnels de sante semblaient les plus a meme de provoquer l’adhesion au depistage chez les patientes les consultant. Discussion et conclusion Axer la communication sur les populations defavorisees et promouvoir le depistage organise en lieu et place du depistage individuel par les professionnels de sante eux-memes pourrait augmenter l’adhesion au depistage organise dans les Yvelines.

Introduction Le pronostic des patients âges atteints de cancer est difficile a evaluer du fait de la fragilite, des comorbidites et du cancer. Les marqueurs biologiques de routine sont rarement consideres comme marqueurs pronostiques car ils ont une valeur predictive faible par rapport aux facteurs cliniques. Des index composites associant plusieurs variables biologiques de routine ont ete construits. L’objectif etait d’evaluer la valeur predictive de biomarqueurs courants sur la mortalite chez des patients âges atteints de cancer. Methodes Une analyse poolee des donnees de trois etudes de cohortes multicentriques a ete effectuee. Les sujets inclus etaient âges de 70 ans ou plus, avec un cancer solide. Les donnees recueillies etaient les donnees sociodemographiques, cliniques, les caracteristiques de la tumeur, et le statut vital a un an. Les parametres biologiques etudies etaient la CRP, l’albumine et des index prenant en compte ces deux parametres : le « Glasgow Prognostic Score » (GPS) et le « modified GPS » (mGPS). Le GPS se decomposait en trois categories (0 : CRP ≤ 10 mg/L, albumine ≥ 35 g/L ; 1 : CRP ≤ 10 mg/L et albumine 10 mg/L et albumine ≥ 35 g/L ; 2 : CRP > 10 mg/L et albumine 10 mg/L ; 2 : CRP > 10 mg/L et albumine Resultats Au total, 1800 patients ont ete inclus, ELCAPA : n = 543, PHRC Aquitaine : n = 253, ONCODAGE : n = 1004 ; âge moyen : 78,5 ± 5,5 ans ; 61,7 % d’hommes ; 28,9 % metastatiques ; localisations les plus frequentes : sein (34,9 %) et colon-rectum (17,7 %) ; 70,7 % de patients reperes a risque de fragilite par le G8. Le taux de survie etait de 71,1 %. Les GPS et mGPS etaient associes au deces (GPS = 1 : HR ajuste = 2,70 [IC95 % : 2,01–3,62] et GPS = 2 : 4,39 [3,27–5,90] ; mGPS = 1 : 1,91 [1,44–2,52] et mGPS = 2 : 3,09 [2,42–3,96]). L’ajout du GPS ou du mGPS au modele ameliorait sa discrimination (C de Harrell = 0,82 [0,80–0,83] et D de Somers = 0,63 pour le modele sans biomarqueur ; C de Harrell = 0,84 [0,82–0,85 ; p Conclusion Le GPS et le mGPS, index combinant deux marqueurs biologiques de routine, la CRP et l’albumine ameliorent la valeur predictive du modele clinique. Ces index pourraient etre utilises dans l’aide a la decision et l’evaluation du pronostic chez les patients âges atteints de cancer.

Objectives: To evaluate the predictive ability of four clinical frailty indexes as regards one-year rapid cognitive decline (RCD — defined as the loss of at least 3 points on the MMSE score), and one-year institutional admission (IA) and mortality respectively; and to measure their agreement for identifying groups at risk of these severe outcomes. Design: One-year follow-up and multicentre study of old patients participating in the SAFEs cohort study. Setting: Nine university hospitals in France. Participants: 1,306 patients aged 75 or older (mean age 85±6 years; 65% female) hospitalized in medical divisions through an Emergency department. Measurements: Four frailty indexes (Winograd; Rockwood; Donini; and Schoevaerdts) reflecting the multidimensionality of the frailty concept, using an ordinal scoring system able to discriminate different grades of frailty, and constructed based on the accumulation of identified deficits after comprehensive geriatric assessment conducted during the first week of hospital stay, were used to categorize participants into three different grades of frailty: Gl — not frail; G2 — moderately frail; and G3 — severely frail. Comparisons between groups were performed using Fisher's exact test. Agreement between indexes was evaluated using Cohen's Kappa coefficient. Results: All patients were classified as frail by at least one of the four indexes. The Winograd and Rockwood indexes mainly classified subjects as G2 (85% and 96%), and the Donini and Schoevaerdts indexes mainly as G3 (71% and 67%). Among the SAFEs cohort population, 250, 1047 and 1,306 subjects were eligible for analyses of predictability for RCD, 1-year IA and 1-year mortality respectively. At 1 year, 84 subjects (34%) experienced RCD, 377 (36%) were admitted into an institutional setting, and 445 (34%) had died With the Rockwood index, all subjects who expenenced RCD were classified in G2; and in G2 and G3 when the Donini and Schoevaerdts indexes were used No significant difference was found between frailty grade and RCD, whereas frailty grade was significantly associated with an increased risk of IA and death, whatever the frailty index considered. Agreement between the different indexes of frailty was poor with Kappa coefficients ranging from −0.02 to 0.15. Conclusion: These findings confirm the poor clinimetric properties of these current indexes to measure frailty, underlining the fact that further work is needed to develop a better and more widely-accepted definition of frailty and therefore a better understanding of its pathophysiology

Resume Objectifs Le but de l'etude etait de comparer la douleur postoperatoire des patientes ayant eu une hysterectomie par voie vaginale selon le procede d'hemostase, fils resorbables ou thermofusion. Patientes et methodes Etude retrospective realisee chez les 60 dernieres patientes ayant beneficie d'une hysterectomie par voie vaginale pour une pathologie benigne dans le service de chirurgie gynecologique du CHI de Poissy–Saint-Germain-en-Laye jusqu'en mars 2006. Parmi ces patientes, 32 avaient beneficie d'une hemostase par fils et 28 de la thermofusion. Les criteres etudies etaient la douleur postoperatoire, la consommation morphinique totale et les durees du traitement antalgique, de l'hospitalisation et du temps operatoire. Resultats La douleur postoperatoire des 24 premieres heures etait plus de deux fois inferieure avec l'utilisation de la thermofusion, que ce soit en periode postoperatoire immediate ou a 24 heures. Par ailleurs, la consommation morphinique totale etait aussi significativement inferieure par l'utilisation de la thermofusion. Discussion et conclusion Cette etude pilote temoigne que, en terme de douleur dans le postoperatoire immediat, la technique par thermofusion est seduisante. D'autres etudes prospectives et randomisees permettraient de le confirmer et de conclure egalement en terme de duree d'hospitalisation, de qualite de vie des patientes et de cout en terme de sante publique.

Summary Objectives The aim of this study was to identify early indicators of prolonged hospital stays by elderly patients. Methods This prospective pilot study, conducted at Strasbourg University Hospital, included patients aged 75 years or older who were hospitalized via the emergency department (SAFES cohort: Sujet Âge Fragile: Evaluation et suivi, that is, Frail Elderly Subjects: Evaluation and Follow-up). A gerontologic evaluation of these patients during the first week of their hospitalization furnished the data for an exact logistic regression. Two definitions were used for prolonged hospitalization: 30 days and a composite number adjusted for diagnosis-related group according to the French classification (f-DRG). Results The analysis examined 137 hospitalizations. More than two thirds of the patients were women (73%), with a mean age of 84 years. Twenty-four hospitalizations (17%) lasted more than 30 days, but only 6 (4%) lasted beyond the DRG-adjusted limit. No social or demographic variables appeared to affect the length of stay, regardless of the definition of prolonged stay. No indicator was associated with the 30-day limit, but clinical markers were linked to prolongation assessed by f-DRG adjustment. A “risk of malnutrition” (OR = 14.07) and “mood disorders” (OR = 2,5) were both early markers for prolonged hospitalization. Although not statistically significant, “walking difficulties” (OR = 2.72) and “cognitive impairment” (OR = 5.03) appeared to be associated with prolonged stays. No association was seen with either the variables measured by Katz's Activities of Daily Living Index or its course during hospitalization. Conclusion Our study shows that when generally recognized indicators of frailty are taken into account, a set of simple items enables a predictive approach to the prolongation of emergency hospitalizations of the elderly.

Objectif Estimation de la dependance, description des conditions de vie (aides apportees par des professionnels et l’entourage non professionnel, equipement technique et amenagement du logement), des besoins non combles et des perspectives de maintien a domicile des personnes âgees vivant a domicile en Alsace. Methode Realisee en 1996-97 en Alsace, cette enquete se compose de deux parties. Une enquete postale sur un echantillon de 15 600 personnes âgees de 75 ans et plus, tire au sort a partir des listes d’affiliation des caisses de retraites. Cette enquete apporte une image fiable de la population en terme de desavantage selon la classification de Colvez. Dans un second temps, une enquete a domicile aupres de 1 259 personnes selectionnees essentiellement parmi les plus desavantagees au sein de l’echantillon initial, a ete realisee afin de decrire leurs conditions de vie et leur dependance. La situation des differents groupes de dependance (GIR) a ete comparee en matiere d’aides humaines, d’equipements techniques et de conditions de logement. Resultats On a estime la population des 75 ans ou plus vivant a domicile a pres de 71 000 individus en Alsace. Selon l’enquete postale, la grande majorite (68 %) vit sans desavantage. Mais 6 000 personnes (8 %) ont besoin d’une aide pour la toilette et l’habillage dont 1 500 (2 %) restent confinees au lit ou au fauteuil. Selon l’enquete a domicile, entre 4 350 et 5 400 appartiennent aux groupes iso-ressources (GIR) 1 a 3. Dans notre enquete, la dependance est liee a l’âge et au sexe. L’aide apportee par l’entourage familial et/ou les proches est systematique et concerne l’ensemble des activites de la vie quotidienne, meme les plus intimes. Les professionnels n’interviennent le plus souvent qu’en complement et pour des activites techniques. Les services de gardes a domicile et en soins infirmiers ne concernent que les plus dependants. Chez ceux-ci, l’aide de l’entourage est trois fois plus important que l’aide des professionnels en terme de nombre d’activites prises en charge. Seuls 11 % des personnes GIR 1 a 3 considerent etre insuffisamment aides. L’equipement technique des logements est correcte, exclusion faite de la telealarme. Dans ce cas, l’absence d’equipement correspond soit a un manque d’information soit a un refus d’amenagement. Plus de 80 % des personnes âgees sont satisfaites de cette situation et n’envisagent pas d’entree en institution. Conclusion Cette etude confirme l’importante solidarite des familles et des proches envers leurs aines.

La notion de fragilite est entree progressivement dans le vocabulaire geriatrique du fait de l’identification d’une sous-population de personnes âgees a plus grand risque de mortalite et d’incapacite. En deux decennies environ, sa definition a progressivement evolue, mais aujourd’hui encore, elle a du mal a faire consensus. Cependant, cliniciens, chercheurs et responsables politiques restent unanimes sur la necessite de developper des outils de depistage precoce afin de mettre en place une strategie de prise en charge adaptee et une demarche preventive coherente.

Resume Objectif. – Evaluer a moyen terme la tolerance et l'efficacite des cures de cystocele par voie vaginale par interposition de prothese de polypropylene monofilament sous-vesicale transversale libre. Patientes et methodes. – Notre etude interesse une serie consecutive de 40 patientes operees selon cette nouvelle technique entre mars 2001 et septembre 2002. Apres dissection de la cystocele, une prothese de polypropylene (Gynemesh ® , Gynecare, Ethicon, Johnson & Johnson, France) prealablement decoupee, est positionnee et ajustee sous la vessie sans fixation, les extensions prothetiques laterales etant introduites dans les espaces paravesicaux au contact de l'arc tendineux du fascia pelvien. Resultats. – Les patientes presentaient des cystoceles de stade II (20 %) ou III (80 %) selon la classification POP-Q. Trente-deux patientes presentaient un prolapsus associe de l'etage perineal moyen ou posterieur (82,5 %). Trente patientes souffraient d'une incontinence urinaire d'effort (75 %). L'âge moyen etait de 63,9 ans (51–78). La faisabilite de l'intervention etait de 100 %. La duree moyenne d'une cure de cystocele etait de 20 minutes ± 2,2 (16 a 24 minutes). Le recul moyen est de 16,4 mois ± 4,7 (12–24). Le taux de complication precoce est de 7,5 % (2 cas d'erosion vaginale corriges par excision vaginale et prothetique et 1 cas de desunion precoce de la colporraphie ayant necessite l'ablation de la prothese). Aucune infection prothetique n'a ete detectee. Le taux de succes objectif est de 95 % (cystocele stade 0 ou 1 sans gene fonctionnelle). Quatre-vingt-quinze pour cent des operees ont un indice de satisfaction depassant 80 % a six mois. Discussion et conclusions. – L'interposition d'une prothese de polypropylene sous-vesicale transversale libre par voie vaginale semble etre une excellente procedure pour le traitement chirurgical definitif des prolapsus vesicaux initiaux ou recidives. Cette technique se caracterise par sa simplicite, sa faisabilite, sa faible morbidite et son caractere mini-invasif. Elle permet une correction durable des composantes centrale et laterale du prolapsus vesical avec une excellente efficacite et une tolerance satisfaisante a moyen terme.

Introduction En cancerologie, la survie globale (SG) demeure le critere de jugement gold standard demontrant un benefice clinique. Des etudes montrent des limites a son interpretation pour la population âgee (deces lies a des causes autres, comorbidites, etc.) et indiquent la pertinence de recourir a des criteres de jugement alternatifs. Il n’existe cependant aucune harmonisation ou consensus valide pour le choix et la definition des criteres de jugement principaux en oncogeriatrie. Afin d’identifier les typologies de criteres de jugement utilises dans les essais en oncogeriatrie, l’intergroupe cooperateur Dialogue Intergroupe pour la personnALisation de la prise en charge en OncoGeriatrie (DIALOG) a realise un recensement des essais cliniques menes en France dans ce domaine. Methode Cette recherche a ete conduite par un groupe d’experts (cliniciens et epidemiologistes) sur la periode 1998–2015. Les sources de donnees utilisees etaient les suivantes : registre des essais cliniques de l’INCa, groupes cooperateurs et societes savantes dont Societe francophone d’oncogeriatrie (SOFOG), Groupe d’oncogeriatrie UNICANCER (GERICO), Association de recherche sur les cancers dont gynecologiques (ARCAGY-GINECO), Groupe francais de pneumo-cancerologie (GFPC), Federation francophone de cancerologie digestive (FFCD), Groupe cooperateur multidisciplinaire en oncologie (GERCOR). Les informations recueillies portaient sur la phase de l’etude, les criteres de jugement principaux et secondaires. Le critere de jugement principal a ete decrit selon sa nature, unique ou combinaison : composite (ex. : survie sans progression), co-primaire (ex. : reponse tumorale et tolerance), ou co-primaire et composite (ex. : survie globale et qualite de vie), autre (non compose et non double). La finalite « clinique » du critere de jugement a ete categorise selon trois modalites : « cancer » (ex. : survie globale ; progression tumorale, toxicite), « geriatrie » (ex. : qualite de vie, autonomie), « autres » (ex. : faisabilite du traitement, adhesion du patient au traitement). Resultats Au total 102 essais cliniques ont ete identifies. Pour la majorite, il s’agissait d’essais cliniques de phase II ( n = 46) ou de phase III ( n = 31). Dans les essais ayant un critere principal lie au cancer ou a la geriatrie, l’utilisation de criteres composites et co-primaires a ete frequente (54 essais [59,3 %] et 10 essais [11 %] respectivement). Parmi la totalite des essais, 64 utilisaient un critere de jugement principal lie au cancer (62,7 %), 27 lie a l’aspect geriatrie (26,5 %), et 20 un critere « autre » (19,6 %). Conclusion Nous montrons une heterogeneite dans le choix des criteres de jugement principaux ainsi que dans leur definition meme si l’exhaustivite du recueil des essais en oncogeriatrie est une limite potentielle dans ce travail. Cette heterogeneite s’observe tant sur le plan du choix du domaine du critere de jugement que sur sa construction. Une harmonisation de ces criteres dans les essais cliniques en oncogeriatrie est necessaire afin de faciliter l’interpretation, la comparaison et la valorisation des etudes publiees, mais egalement pour la mise en œuvre de futures etudes et pour faciliter la transposition des resultats dans la pratique clinique quotidienne. Dans ce contexte, un projet de recherche pluridisciplinaire et international (DATECAN-Elderly) est actuellement en cours afin d’elaborer des recommandations pour la definition des criteres de jugement dans les essais en oncogeriatrie.

Resume Introduction. – Les candidemies, qui affectent principalement les patients neutropeniques d’oncohematologie et les malades fragilises de reanimation, peuvent egalement etre diagnostiquees chez des personnes âgees fragiles en geriatrie. Exegese. – Les auteurs rapportent quatre observations de candidemies mises en evidence chez des patients âges, polypathologiques et dependants, devant une fievre persistante ou recidivante apres une antibiotherapie a large spectre. Ces patients ont ete traites par fluconazole avec sterilisation des hemocultures sur milieu fongique en quelques jours. Trois des quatre malades sont decedes dans les semaines qui ont suivi le traitement antifongique en raison de la gravite des maladies associees. Conclusion. – ces observations montrent qu’il faut penser a une candidemie en cas de fievre persistante chez une personne âgee fragile. Le fluconazole, qui est aussi efficace que l’amphotericine B et bien tolere par le sujet âge, represente le traitement de premiere intention des candidemies des patients non neutropeniques.

Resume Propos. – Les fractures spontanees, de fatigue ou par insuffisance osseuse, sont bien connues en milieu rhumatologique, mais peu etudiees en milieu geriatrique. Methodes. – Nous avons realise une etude clinique prospective de 30 mois dans les unites de soins de longue duree de la Societe de gerontologie de l'Est (70 etablissements, 11 495 lits). Resultats. – Sur les 30 etablissements ayant detecte des fractures spontanees (soit 3 052 lits), nous avons releve 67 fractures spontanees (cinq de fatigue au niveau des pieds et 62 par insuffisance osseuse). Chez ces patients d'âge moyen 85 ± 7 ans, le point commun est le confinement au lit ou au fauteuil. La frequence des fractures spontanees, calculee en fonction du nombre de patients admis de facon consecutive dans ces unites de soins de longue duree, est estimee a 0,34 % (calcul prenant en compte 11 495 lits) et 1,3 % (calcul prenant en compte 3 052 lits). Les fractures des os longs sont particulierement frequentes (col du femur : 15, tibia et/ou perone : 14, diaphyse femorale : 13, humerus : 11). Les fractures de la diaphyse femorale ont le plus mauvais pronostic vital avec sept deces sur 13 versus deux deces sur 15 en cas de fracture du col du femur ( p Conclusion. – Contrairement aux fractures observees en milieu rhumatologique chez des patients jeunes et valides, les fractures par insuffisance osseuse observees en unites de soins de longue duree chez les personnes âgees concernent principalement les os longs et sont de mauvais pronostic. Les moyens de prevention restent a definir.

Background: The additive effect of non-steroidal anti-inflammatory drugs administered with propacetamol after major orthopaedic surgery has not been studied. Thus, we performed a prospective, placebo-controlled study to assess the analgesic effects of ketoprofen in patients undergoing spinal fusion surgery and receiving propacetamol. Methods: Fifty patients undergoing spinal fusion surgery received either 100 mg of ketoprofen every 8 h or a placebo, postoperatively. All patients received propacetamol and morphine (intravenous titration followed by patient-controlled analgesia (PCA) over 24 h). Pain was assessed using a visual analogue pain scale (VASpi). Data are mean±SD. Results: During morphine titration, ketoprofen did not significantly reduce the dose of morphine (8±6 vs 11±4 mg, NS) whereas it significantly decreased VASpi (P

The fragile X syndrome results from transcriptional silencing of the FMR1 gene and the absence of its encoded FMRP protein. Two autosomal homologues of the FMR1 gene, FXR1 and FXR2, have been identified and the overall structures of the corresponding proteins are very similar to that of FMRP. Using antibodies raised against FXR1P, we observed that two major protein isoforms of relative MW of 78 and 70 kDa are expressed in different mammalian cell lines and in the majority of mouse tissues. In mammalian cells grown in culture as well as in brain extracts, both P78 and P70 isoforms are associated with mRNPs within translating polyribosomes, similarly to their closely related FMRP homologues. In muscle tissues as well as in murine myoblastic cell lines induced to differentiate into myotubes, FXR1P78 and P70 isoforms are replaced by novel unpredicted isoforms of 81‐84 kDa and a novel FXR1 exon splice variant was detected in muscle RNA. While P81‐84 isoforms expressed after fusion into myotubes in murine myoblast cell lines grown in culture are associated with polyribosomes, this is not the case when isolated from muscle tissues since they sediment with lower S values. Immunohistochemical studies showed coexpression of FMRP and FXR1P70 and P78 in the cytoplasm of brain neurons, while in muscle no FMRP was detected and FXR1P81‐84 were mainly localized to structures within the muscle contractile bands. The complex expression pattern of FXR1P suggests tissue-specific expression for the various isoforms of FXR1 and the differential expression of FMRP and FXR1Ps suggests that in certain types of cells and tissues, complementary functions may be fulfilled by the various FMRP family members.

En 2010, le taux de participation au depistage organise (DO) du cancer du sein etait de 52 % au niveau national et de 40 % dans le departement des Yvelines [1], inferieur aux objectifs du Plan Cancer (70 %) [2].

The present study investigated the effect of EBV on gene expression and protein synthesis of IL-1 and its natural IL-1R antagonist (IL-1Ra) in human peripheral blood neutrophils. EBV induced a rapid accumulation of IL-1 and IL-lRa mRNA in neutrophils that was associated with the later appearance of considerable amounts of IL-1alpha, IL-1beta, and IL-Ra proteins. Approximately 3200 and 610 times more IL-Ra than IL-1alpha a or IL-1beta, respectively, was secreted by neutrophils in response to EBV. The effect induced by EBV cannot reflect an overall metabolic activity of neutrophils, since EBV failed to induce granulocyte-macrophage OF synthesis. Heat-inactivated virus was unable to stimulate cytokine synthesis, whereas UV-irradiated virus retained the full IL-1- and IL-1Ra-inducing potential of the native particle. Furthermore, pretreatment of cells with cycloheximide or phosphonoacetic acid did not abrogate the effect of EBV, suggesting that EBV does not penetrate the cell, but that a virion's structural molecule is required to induce such an effect. In this respect, neutralization of the viral particles with the mAb 72A1, which is known to react with glycoprotein gp350 of the viral envelope, inhibits the production of IL-1 and IL-1Ra, suggesting that gp350 could be involved in this process. Thus, the elevated levels of IL-1Ra detected for EBV-stimulated neutrophils might be part of a mechanism used by the virus to evade the immune system.

Even though the efforts in research have detailed further the physiopathology and the dynamics of the frailty process an operational definition of frailty is still far from being unequivocal. Studies carried out from the SAFEs cohort study allowed a pragmatic approach in the identification of the at-risk groups for the lost of independency during the hospital stay and factors influencing their future at short-, mid- and long-term. Based upon these results, we propose to discuss the relevance of the current operational indicators of frailty in order to show that clinical markers or indicators are insufficient to differentiate the frailty process from normal ageing. Finally we give rise to the imperative necessity to detect frailty at a preclinical stage with the help of biological and more particularly inflammatory markers.

Objectives: The aim of the study was to identify factors related to institutionalisation within one-year follow up of subjects aged 75 or over, hospitalised via the emergency department (ED). Design: Prospective multicentre cohort. Setting: Nine French university teaching hospitals. Participants: One thousand and forty seven (1 047) non institutionalised subjects aged 75 or over, hospitalised via ED. A sub-group analysis was performed on the 894 subjects with a caregiver. Measurements: Patients were assessed using Comprehensive Geriatric Assessment (CGA) tools. Cox survival analysis was performed to identify predictors of institutionalisation at one year. Results: Within one year after hospital admission, 210 (20.1%) subjects were institutionalised. For the overall study population, age >85 years (HR 1.6; 95%CI 1.1-2.1; p=0.005), inability to use the toilet (HR 1.6; 95%CI 1.1-2.4; p=0.007), balance disorders (HR 1.6; 95%CI 1.1-2.1; p=0.005) and presence of dementia syndrome (HR 1.9; 95%CI 1.4-2.6; p

Background The objective of the study was to identify factors predictive of 6-month institutionalization or mortality in frail elderly patients after acute hospitalization. Methods A prospective cohort of elderly subjects 75 years and older was set up in nine French teaching hospitals. Data obtained from a comprehensive geriatric assessment were used in a Cox model to predict 6-month institutionalization or mortality. Institutionalization was defined as incident admission either to a nursing home or other long-term care facility during the follow-up period. Results Crude institutionalization and death rates after 6 months of follow-up were 18% and 24%, respectively. Independent predictors of institutionalization were: living alone (HR = 1.83; 95% CI = 1.27–2.62) or a higher number of children (HR = 0.86; 95% CI = 0.78–0.96), balance problems (HR = 1.72; 95% CI = 1.19–2.47), malnutrition or risk thereof (HR = 1.93; 95% CI = 1.24–3.01), and dementia syndrome (HR = 1.88; 95% CI = 1.32–2.67). Factors found to be independently related to 6-month mortality were exclusively medical factors: malnutrition or risk thereof (HR = 1.92; 95% CI = 1.17–3.16), delirium (HR = 1.80; 95% CI = 1.24–2.62), and a high level of comorbidity (HR = 1.62; 95% CI = 1.09–2.40). Institutionalization (HR = 1.92; 95% CI = 1.37–2.71) and unplanned readmission (HR = 4.47; 95% CI = 3.16–2.71) within the follow-up period were also found as independent predictors. Conclusion The main factors predictive of 6-month outcome identified in this study are modifiable by global and multidisciplinary interventions. Their early identification and management would make it possible to modify frail elderly subjects’ prognosis favorably.

Apres les phases successives de mise en place des unites pilotes en oncogeriatrie, puis de maillage systematique du territoire, la pratique de l’oncogeriatrie entre a present dans le quotidien des oncologues. A la lumiere de notre experience d’unites pilote, puis d’unites de coordination regionale, nous faisons ici le point tant sur les changements de pratique suscites par cette politique nationale, que sur les ecueils rencontres et les enjeux des annees a venir.

Genetic recombination near the fragile X locus (Xq27.3) has frequently been a problem in linkage studies of families in which the fragile X is segregating. This case report illustrates the resolution of a difficult situation in a fragile X family for whom cytogenetic studies were inconclusive and where recombination had twice confounded attempts at prenatal DNA diagnosis by RFLP analysis. Using a newly developed DNA probe, StB12.3, for direct detection of DNA instability in the fragile X locus, the presence of the fragile X was ascertained definitively in a prenatal DNA sample.

To identify predictive factors for 2-year mortality in frail elderly patients after acute hospitalisation, and from these to derive and validate a Mortality Risk Index (MRI). A prospective cohort of elderly patients was set up in nine teaching hospitals. This cohort was randomly split up into a derivation cohort (DC) of 870 subjects and a validation cohort (VC) of 436 subjects. Data obtained from a Comprehensive Geriatric Assessment were used in a Cox model to predict 2-year mortality and to identify risk groups for mortality. A ROC analysis was performed to explore the validity of the MRI. Five factors were identified and weighted using hazard ratios to construct the MRI: age 85 or over (1 point), dependence for the ADL (1 point), delirium (2 points), malnutrition risk (2 points), and co-morbidity level (2 points for medium level, 3 points for high level). Three risk groups were identified according to the MRI. Mortality rates increased significantly across risk groups in both cohorts. In the DC, mortality rates were: 20.8% in the low-risk group, 49.6% in the medium-risk group, and 62.1% in the high-risk group. In the VC, mortality rates were respectively 21.7, 48.5, and 65.4%. The area under the ROC curve for overall score was statistically the same in the DC (0.72) as in the VC (0.71). The proposed MRI appears as a simple and easy-to-use tool developed from relevant geriatric variables. Its accuracy is good and the validation procedure gives a good stability of results.

Background: The preservation of autonomy and the ability of elderly to carry out the basic activities of daily living, beyond the therapeutic care of any pathologies, appears as one of the main objectives of care during hospitalization. Objectives: To identify early clinical markers associated with the loss of independence in elderly people in short stay hospitals. Methods: Among the 1,306 subjects making up the prospective and multicenter SAFEs cohort study (Sujet Agé Fragile: Évolution et suivi—Frail elderly subjects, evaluation and follow-up), 619 medical inpatients, not disabled at baseline and hospitalized through an emergency department were considered. Data used in a multinomial logistic regression were obtained through a comprehensive geriatric assessment (CGA) conducted in the first week of hospitalization. Dependency levels were assessed at baseline, at inclusion and at 30days using Katz's ADL index. Baseline was defined as the dependence level before occurrence of the event motivating hospitalization. To limit the influence of rehabilitation on the level of dependence, only stays shorter than 30days were considered. Results: About 514 patients were eligible, 15 died and 90 were still hospitalized at end point (n=619). Two-thirds of subjects were women, with a mean age of 83. At day 30 162 patients (31%) were not disabled; 61 (12%) were moderately disabled and 291 severely disabled (57%). No socio-demographic variables seemed to influence the day 30 dependence level. Lack of autonomy (odds ratio (OR)=1.9, 95% confidence interval (CI)=1.2-3.6), walking difficulties (OR=2.7, 95% CI=1.3-5.6), fall risk (OR=2.1, 95% CI=1.3-6.8) and malnutrition risk (OR=2.2, 95% CI=1.5-7.6) were found in multifactorial analysis to be clinical markers for loss of independence. Conclusions: Beyond considerations on the designing of preventive policies targeting the populations at risk that have been identified here, the identification of functional factors (lack of autonomy, walking difficulties, risk of falling) suggests above all that consideration needs to be given to the organization per se of the French geriatric hospital care system, and in particular to the relevance of maintaining sector-type segregation between wards for care of acute care and those involved in rehabilitation

The purpose of the study was to compare the postoperative pain of patients who had a hysterectomy through vaginal route according to the process of binding: wire or electrosurgical bipolar vessel sealing.Retrospective study carried out in the 60 last patients who underwent a hysterectomy by vaginal route for a benign pathology in the gynaecological service of surgery of the CHI Poissy-Saint-Germain-en-Laye until March 2006. Among these patients, 32 had profited from a binding by wire and 28 of the electrosurgical bipolar vessel sealing. The studied criteria were the post-operative pain, total morphine consumption and the durations of the analgesic treatment, the hospitalisation and intervention time.The postoperative pain in the first 24 hours was twice lower using thermofusion; it was valid in immediate post-operative period and after 24 hours. In addition, total morphine consumption was also significantly lower using thermofusion.This pilot study shows that the electrosurgical bipolar vessel sealing allows a reduction in the pain into the immediate postoperative period. Other prospective and randomised studies would allow it and conclude on the duration of hospitalisation, the quality of life from the patients and the cost in terms of public health.

Summary Pyogenic liver abscesses are mainly caused by digestivediseases in the biliary tract or less often from a portal seeding. Bacteria can also reach the liver by other mechanisms: local extension from an inflammatory process, direct inoculation, and bacteremia. With 10 to 35% of cases, cryptogenic abscesses remain frequent. We relate 2 cases of pyogenic hepatic abscesses with a strong suspicion of dental etiology linked to the isolated bacteria ( Fusobacterium . spp and Streptococcus anginosus ), the patients' marked dental diseases and the negative results of other etiologic investigations. A thorough clinical and radiological dental exam is required before diagnosing a cryptogenetic abscess, when confronted to hepatic abscesses of unknown etiology, above all if Fusobacteria is isolated.

Our aim was to describe the living conditions of disabled elderly subjects aged 75 years and more living at home.This study was conducted in 1996-97 in the Alsace region in France and included two parts. First, a sample survey was mailed to 15,600 subjects randomly selected from a pension funds list. This survey provided with a reliable representation of the study population in terms of disabilities using the Colvez classification. In the second part, the most disabled individuals were selected and, among them, 1,259 subjects were visited at home. Their disabilities and living conditions were noted using a predefined set of questions.An estimated 71,000 subjects aged 75 years and more lived at home in the study region. The vast majority were free of significant disability. Help to wash and dress was needed by 6,000 until 1,500 were bedridden or confined to an armchair. Between 4,350 and 5,400 met the criteria for iso-resource grades (IRG) 1 to 3. Disability was associated with age, female gender, cognitive impairment and some social and professional characteristics. Family support was routine in almost every aspect of everyday life including personal hygiene. Professional support was mostly limited to technical interventions. Professional nursing care concerned only the most dependent persons. Nevertheless, needs for help in home and social activities remained high even in the least dependent individuals and were strongly age-dependent. Only 10% of individuals with IRG 1 to 3 complained of inadequate help. More than 80% of the elderly felt comfortable with their living conditions at home and were not thinking of moving from home to an institution for old people.The present study confirms the important commitment of family members and their close relationships toward their elderly.

Most of the antibiotic-associated diarrhea (AAD) cases result from a transient disturbance in the function of the normal intestinal flora and are spontaneously solved when discontinuing the antibacterial therapy. However, a mild diarrhea lasting several days may induce a dehydration or worsen a denutrition in frail elderly people.The incidence of AAD varies between 5 and 25% depending on the concerned antibiotic. Only 10-20% of all AAD cases are caused by infection, especially with Clostridium difficile, for which advanced age is a major risk factor. The first biological exam to perform when severe AAD or in frail people is the detection of C. difficile toxins, especially in elderly patient treated with beta-lactam antibiotics. Nevertheless, other infectious organisms causing AAD may be considered, as Staphylococcus aureus when predominant in stool cultures from patients treated with fluoroquinolones or as Klebsiella oxytoca when isolated in bloody diarrhea from patients treated with ampicillin. Elevated fecal counts of Candida spp. found in patients treated with antibiotics is rather the consequence of therapy than the cause of AAD. The prevention of AAD is based on a rational antibiotic use to avoid endogenous selection of C. difficile and on the improvement of the hygiene measures to limit the exogenous transmission of the bacteria or related spores by spoiled hands.Simultaneous prescription of non-pathogenic living organisms, capable of re-establishing the equilibrium of the intestinal flora, should be better described, especially in elderly people, because of its important economic impact.

Clinical examination (history and physical examination) is not considered to be a useful tool in the diagnosis of ectopic pregnancy (EP). In this systematic review we aimed to evaluate its value when ancillary tests are not readily available or when they are equivocal. Suspicion of EP is based on the presence of one or more of the following signs: vaginal bleeding, acute pelvic pain, or any risk factors for EP occurring in a pregnant woman. Detection of early pregnancy by urinary or serum hCG testing must be systematic because neither medical history nor physical examination can rule out early pregnancy with a high level of confidence. No isolated sign has sufficient diagnostic accuracy to rule out EP. In presence of vaginal bleeding without pain and if abdominal and pelvic examination are normal the risk of EP is very low. The presence of spontaneous pain moderate to severe, peritoneal signs, or definite pain during digital cervical mobilization increase the probability of EP. Absence of these signs does not rule out EP but tend to eliminate tubal rupture. In the presence of these signs one may consider an emergency transfer in a specialized center. In their absence, suspicion of EP may have outpatient diagnosis procedures.

To evaluate mid term results, tolerance and efficiency of interposition of a tension-free polypropylene monofilament mesh by vaginal approach for the repair of cystoceles.Fourty consecutive women underwent this new procedure between March 2001 and September 2002. After complete dissection of the cystocele, the polypropylene mesh (Gynemesh), Gynecare, Ethicon, JohnsonJohnson, France), proper cut-out was positioned under the bladder without any fixation. The lateral extensions of the mesh where introduced in the para-vesical spaces in contact with the arcus tendinus fascia pelvis.Before surgery all patients had cystocele of more or equal than grade II according to the POP-Q classification. Eight had grade II cystocele (20%) and 32 had grade III cystocele (80%). Thirty women had associated posterior or median prolapse (82.5%). Thirty women had urinary incontinence (75%). Mean age was 63.9 years (51-78). The procedure was performed without any difficulty in all cases. Duration of a cystocele cure procedure was 20 min +/- 2.2 (16-24). Mean follow-up is 16.4 months +/- 4.7 (12-24). The early complication rate was 7.5% (two vaginal erosions and one complete exposition of the mesh which requires secondary ablation). There was no mesh infection. The success rate was 95%. The satisfaction index overpasses 80% in 95% of our patients 6 months after the cystocele repair.The interposition of a sub-vesical transversal tension-free polypropylene mesh by the vaginal route seems to be an excellent procedure in the definitive surgical treatment of grades II and III anterior vaginal wall prolapse. This new procedure is simple, mini-invasive, reproducible and efficient with low morbidity and good tolerance.

The aim of this study was to specify the characteristics of enterobacterial urinary infections producing wide spectrum beta-lactamase (WSBL) and the management strategies for these patients infected in geriatric wards.The prevalence, bacteriological characteristics and treatment regimens of enterobacterial urinary infections producing WSBL, diagnosed in a geriatric department of internal medicine from May 1977 to April 2001, were studied retrospectively.Sixty-six enterobacterial urinary infections producing WSBL were diagnosed, with 53 (80%) of them acquired in the ward. They represented 1.6% of admissions and concerned 24 men and 42 women (sex ratio: 0.57), with a mean age of 87 years. Their prevalence was of 20 in the 1st year, 11 in the 2nd, 9 in the third and 26 in the 4th year. The mean duration of hospitalization of infected patients was 4.5-fold longer (90 vs. 20 days) and the mortality rate 2-fold higher (32 vs. 14%). Enterobacter aerogenes were responsible for half (46%) of the WSBL urinary infections. The skin was invaded by enterobacteria in 67% and the feces in 57% of cases. More than one third of the urinary infections treated relapsed, and digestive decontamination was only efficient in half of the patients treated.This 4-year study emphasizes the limits of antibiotherapy in eradicating WSBL-producing enterobacteria and the fact that only the strict respect of hygiene by all caregivers (isolation of patients exhibiting WSBL and washing-disinfection of the hands between each patient) limits the incidence of such infections.

The aim of the study was to evaluate the safety and efficacy of the Musset Poitout surgical procedure consisting in an anterior uterosacral ligament transposition and a cervix amputation. The main indication is an uterovaginal prolapse with an isolated elongation of the cervix.A retrospective consecutive series of 20 women with an elongation of uterine cervix undergoing Musset Poitout procedure over a 10 year period between 1990 and 2001 with analysis of per and post operative complications and success. Four Kelly urethral plications were performed in the same time. The patient's ages, time under anesthesia, change in hemoglobin, days of hospitalization, medical illnesses, complications and follow-up were assessed. Failure was defined as a symptomatic elongation of the cervix or a third degree hysterocele on examination.and discussion. The median age of Musset Poitout procedure was 43.9 years (range 23-83). General anaesthesia could be performed in all patients. Mean operation time was 67 minutes (range 40-130). No major per or post operative complications occurred. The average of post-operative bladder cathetherisation was 3.65 days, the average hospital stay was 6.3 days. Complications were insignificant: urinary tract infection in 2, voiding dysfunction in 2. All the patients but 2 were followed for a mean 59 months (range 6-127). There was one recurence (5.5%).In this preliminary assessment the Musset Poitout procedure offered significant avantages in a genital prolapse with elongation of the cervix.

Candidemia, principally affecting neutropenic patients in departments of oncohematology and frail patients in intensive care units, can also be observed in frail elderly people in geriatrics.Authors report four observations of candidemia diagnosed in elderly dependent patients having several different diseases. Clinical sign was a persistent or recurrent fever after a wide-spectrum antibiotic therapy. Patients were treated by fluconazole leading to negative blood cultures in several days. Three out of four patients died within the weeks following antifungal therapy due to severity of associated diseases.These observations show that a diagnosis of candidemia should be made when a persistent fever is observed in a frail elderly person. Fluconazole, as efficient as amphotericin B and well tolerated by elderly people, should be the first treatment of candidemia in non-neutropenic patients.

Spontaneous fractures (stress and bone insufficiency fractures) are well described in young healthy patients; however, few studies were conducted in the elderly.A 30-month prospective clinical and epidemiological survey including elderly patients from long-term nursing homes (LTNH) of the Société de Gérontologie de l'Est (70 centers; 11,495 elderly patients in total) was conducted.Sixty-seven spontaneous fractures were encountered in 30 LTNH (3,052 elderly patients) (five stress fractures of the foot, 62 bone insufficiency fractures). The mean age of bedridden patients was 85 +/- 7 years. The prevalence of spontaneous fractures (calculated from the number of patients admitted consecutively in LTNHs) was 0.34% in the whole population (11,495 beds). When the calculation was based on LTNH reports of spontaneous fractures (3,052 elderly patients), the prevalence reached 1.3%. Fractures of long bones were common in elderly patients and included 15 fractures of the femoral neck, 14 fractures of either the tibia or fibula, 13 fractures of the femoral shaft, and 11 fractures of the humerus. Fractures of the femoral shaft were associated with the highest mortality: seven out of 13 patients died versus two out of 15 patients with regard to fractures of the femoral neck (P0.05).Bone insufficiency fractures have not the same course in young healthy patients as those in elderly nursing home patients: they more often concern long bones and their prognosis is worse. Means of prevention still have to be defined.

The additive effect of non-steroidal anti-inflammatory drugs administered with propacetamol after major orthopaedic surgery has not been studied. Thus, we performed a prospective, placebo-controlled study to assess the analgesic effects of ketoprofen in patients undergoing spinal fusion surgery and receiving propacetamol.Fifty patients undergoing spinal fusion surgery received either 100 mg of ketoprofen every 8 h or a placebo, postoperatively. All patients received propacetamol and morphine (intravenous titration followed by patient-controlled analgesia (PCA) over 24 h). Pain was assessed using a visual analogue pain scale (VASpi). Data are mean+/-SD.During morphine titration, ketoprofen did not significantly reduce the dose of morphine (8+/-6 vs 11+/-4 mg, NS) whereas it significantly decreased VASpi (P0.001). During PCA, ketoprofen significantly reduced morphine consumption (25+/-17 vs 38+/-20 mg, P=0.04) and VASpi (P=0.002). The total postoperative morphine consumption was significantly (33%) reduced with ketoprofen.Ketoprofen reduced morphine requirements and improved postoperative analgesia in patients undergoing major spinal surgery and receiving propacetamol.

Differential display-polymerase chain reaction (DD-PCR) was used to evaluate changes in mRNA expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) treated human neutrophils to better understand how this cytokine affects the functions of neutrophils at the molecular level. Although a variety of cDNA fragments were identified as modulated by GM-CSF with the use of DD-PCR, one fragment in particular, NGS-17 (neutrophil GM-CSF-stimulated fragment #17), was characterized. The NGS-17 fragment hybridized to a 3.8-kb mRNA that encodes for a protein of a predicted molecular mass of 47.6 kDa. After cloning and sequencing, this gene was found to code for the recently sequenced tapasin or TAP-A protein. Immunoprecipitation and immunoblotting studies using anti-tapasin antibodies showed that tapasin is expressed in neutrophils and is associated with the MHC class I-TAP complex. Moreover, tapasin expression was found to be induced by dimethyl sulfoxide and by retinoic acid in HL-60 cells. This is the first report on the expression of tapasin in human neutrophils. It provides novel information, at the molecular level, on how GM-CSF enhances the functions of these cells. J. Leukoc. Biol. 65: 205–210; 1999.

The present study investigated the effect of EBV on gene expression and protein synthesis of IL-1 and its natural IL-1R antagonist (IL-1Ra) in human peripheral blood neutrophils. EBV induced a rapid accumulation of IL-1 and IL-lRa mRNA in neutrophils that was associated with the later appearance of considerable amounts of IL-1alpha, IL-1beta, and IL-Ra proteins. Approximately 3200 and 610 times more IL-Ra than IL-1alpha a or IL-1beta, respectively, was secreted by neutrophils in response to EBV. The effect induced by EBV cannot reflect an overall metabolic activity of neutrophils, since EBV failed to induce granulocyte-macrophage OF synthesis. Heat-inactivated virus was unable to stimulate cytokine synthesis, whereas UV-irradiated virus retained the full IL-1- and IL-1Ra-inducing potential of the native particle. Furthermore, pretreatment of cells with cycloheximide or phosphonoacetic acid did not abrogate the effect of EBV, suggesting that EBV does not penetrate the cell, but that a virion's structural molecule is required to induce such an effect. In this respect, neutralization of the viral particles with the mAb 72A1, which is known to react with glycoprotein gp350 of the viral envelope, inhibits the production of IL-1 and IL-1Ra, suggesting that gp350 could be involved in this process. Thus, the elevated levels of IL-1Ra detected for EBV-stimulated neutrophils might be part of a mechanism used by the virus to evade the immune system.

Objectives The aim of this study was to identify factors predictive of nursing home admission (NHA) over a period of 1 year among elderly subjects with dementia. Methods The study population was drawn from the SAFES cohort that was formed within a national research program into the recruitment of emergency departments in 9 teaching hospitals. Subjects were to have been hospitalized in a medical ward in the same hospital as the emergency department to which they were initially admitted. Subjects who experienced NHA before emergency department admission were excluded. Those with a confirmed diagnosis of dementia were considered in the present analysis. NHA has been defined as the incident admission into either a nursing home or other long term care facility within the follow-up period. Data obtained from a Comprehensive Geriatric Assessment were used in a Cox model to predict 1-year NHA. Results The 425 subjects of the study were 86 ± 6 years old, and were mainly women (63%). NHA rate was 40% (n = 172). Four factors were identified to increase NHA risk: age 85 or older (hazard ratio [HR] = 1.5; 95% confidence interval [CI] = 1.1–2.1), inability to use the toilet (HR = 2.5; 95% CI = 1.5–4.2), balance disorders (HR = 1.5; 95% CI = 1.1–2.1), and living alone (HR = 1.5; 95% CI = 1.1–2.1). Three factors decreased this risk significantly: inability to transfer (HR = 0.5; 95% CI = 0.3–0.8), increased number of children (HR = 0.88; 95% CI = 0.96–0.99), and increased initial Mini-Mental State Examination score (HR = 0.97; 95% CI = 0.8–0.9). Conclusion NHA determinants in dementia are strongly linked to the patient’s own characteristics but also to his or her physical or social environment. Interventions should target both members of the dyad “patient-caregiver” because both are affected by the disease.