Search

Objectives Isoniazid-monoresistant tuberculosis (HR-TB) is the most prevalent form of drug-resistant TB worldwide and in France and is associated with poorer treatment outcomes compared with drug-susceptible TB (DS-TB). The objective of this study was to determine the characteristics of HR-TB patients in France and to compare outcomes and safety of treatment for HR-TB and DS-TB. Methods We performed a case-control multicenter study to identify risk factors associated with HR-TB and compare treatment outcomes and safety between HR-TB patients and DS-TB patients. Results Characteristics of 99 HR-TB patients diagnosed and treated in the university hospitals of Paris, Lille, Caen and Strasbourg were compared with 99 DS-TB patients. Female sex (OR = 2.2; 1.0–4.7), birth in the West-Pacific World Health Organization region (OR = 4.6; 1.1–18.7) and resistance to streptomycin (OR = 77.5; 10.1–594.4) were found to be independently associated with HR-TB. Rates of treatment success did not differ significantly between HR-TB and DS-TB. Conclusions Factors associated with HR-TB are not significant enough to efficiently screen TB patients at risk of HR-TB. The systematic implementation of rapid molecular testing on clinical samples remains the only effective way to make the early diagnosis of HR-TB and adapt treatment.

Resume A l’ere de la telemedecine et des dispositifs connectes, le secteur des dispositifs medicaux est en pleine evolution technologique. En effet, les dispositifs medicaux, grâce aux progres de l’ingenierie biomedicale et du numerique, sont en constante innovation. Cet article vise a expliquer le processus que suit tout nouveau dispositif medical, de sa mise sur le marche a son remboursement par l’assurance maladie. Differents acteurs interviennent lors de ce processus d’evaluation tels que l’Agence nationale de securite du medicament et des produits de sante (ANSM), la Commission nationale d’evaluation des dispositifs medicaux et des technologies de sante (CNEDiMTS, Commission specialisee de la HAS) et le Comite economique des produits de sante (CEPS) jusqu’a la prise de decision finale de remboursement par le Ministre. La CNEDiMTS a pour role d’evaluer l’interet des dispositifs medicaux en vue de leur remboursement par l’assurance maladie afin que les patients malades ou en situation de handicap puissent en beneficier le plus rapidement possible et de la maniere la plus sure.

Background We investigated the association between socioclinical, inflammatory, and metabolic markers and weight gain in people with human immunodeficiency virus (HIV) on combination antiretroviral therapy (cART). Methods Individuals from the COPANA cohort of normal weight (body mass index [BMI], 18.5–24.9 [ calculated as weight in kilograms divided by height in meters squared) at cART initiation who achieved virological suppression (viral load, Results After 36 months of cART, 32 of 158 people with HIV (20%) became overweight or obese (21% female; 65% born in France and 23% born in sub-Saharan Africa; median BMI at cART initiation, 22 [interquartile range, 21–23]). After adjustment, higher BMI, originating from sub-Saharan Africa, living in a couple, and higher soluble tumor necrosis factor receptor 2 and lower adiponectin concentrations at cART initiation were associated with becoming overweight or obese. Conclusion Weight gain on cART is multifactorial. Special attention should be given to migrants from sub-Saharan Africa. Monocyte activation and adipocyte dysfunction at cART initiation affect weight regulation.

OBJECTIVES The aim of the study was to assess whether the timing of combination antiretroviral therapy (cART) initiation, the choice of cART and virological response differ in migrants versus European natives in the north and east of Paris area, after dissemination of French recommendations for universal treatment. METHODS Antiretroviral therapy-naive HIV-1-infected adults with at least two follow-up visits at one of 15 participating centres between 1 January 2014 and 31 March 2015 were included in the study. Factors associated with cART initiation before 31 March 2015, with protease inhibitor (PI)-containing cART among individuals initiating cART, and with 1-year virological success after cART initiation were assessed using multivariable logistic regression models. Sex, age, region of origin [Western Europe, sub-Saharan Africa (SSA) or other], HIV transmission group, baseline AIDS status, CD4 cell count and plasma viral load (VL), and hepatitis B and/or C virus infection were considered in the analyses. RESULTS Among 912 individuals, only 584 (64%) started cART during the study period. After adjustment, migrants from SSA were half as likely to initiate cART and to have a subsequent virological response compared with individuals from Western Europe [adjusted odds ratio (aOR) 0.54; 95% confidence interval (CI) 0.36-0.82; and aOR 0.52; 95% CI 0.28-0.98, respectively]. PI-containing cART was more frequently prescribed in migrants from SSA, in people with lower CD4 cell counts and in people with higher VL. CONCLUSIONS Even in the context of universal cART recommendations and of free access to care, migrants from SSA still have delayed access to cART and a lower virological response. Efforts are still necessary to provide immediate cART to all people living with HIV.

OBJECTIVES We assessed hepatitis B virus (HBV) status in children born to HIV/HBV coinfected women with large access to antiretroviral therapy. METHODS All HIV/HBV coinfected pregnant women from 01 January 2000 to 01 January 2012 were included in the retrospective study (NCT02044068). Antiretroviral therapy during pregnancy and injection of HBV immunoglobulin/vaccine to newborns was recorded. We assessed HBV status of children aged at least 2 years. RESULTS Twenty-one women (35 children) were studied. Twenty-six children (74%) had HBsAb: 22 had received immunoglobulin and 24 had received a complete vaccine (with immunoglobulin in 21 cases); their mothers had been administered lamivudine or tenofovir/emtricitabine during eight and nine pregnancies, respectively. Eight children (23%) were negative for HBsAg, HBsAb, and HBcAb: four (11.5%) had received immunoglobulin and a complete vaccine; in two children, it was not known whether they had received an immunoglobulin injection; in one child, the vaccine was incomplete; and in the last one, it was not known whether he had received immunoglobulin/vaccine. Their mothers had been administered lamivudine or tenofovir/emtricitabine during five and two pregnancies, respectively. No infant has chronic HBV infection (HBsAg) after prenatal mothers' antiretroviral therapy combined with a complete postnatal HBV protection. One child had HBcAb and HBsAb: it was not known whether she had received an immunoglobulin injection; the vaccine was incomplete. The mother had been administered lamivudine during the last trimester of pregnancy. CONCLUSION Antiretroviral therapy in HBV/HIV coinfected women following current national HBV guidelines may prevent mother-to-child-transmission of HBV. Negativity of surrogate markers of vaccine-induced protection is frequent; large studies on long-term protection are needed.

Resume Propos Le diagnostic differentiel entre la maladie tuberculose (granulomatose la plus frequente a l’echelle mondiale) et la sarcoidose (granulomatose rare) est important, car les traitements different completement. Methodes Nous avons evalue prospectivement la presence de granulomes epithelioides a la biopsie de glandes salivaires accessoires (BGSA), critere d’orientation habituel pour le diagnostic de sarcoidose, chez des patients atteints de tuberculose prouvee et vus consecutivement. Resultats Sur notre echantillon de 65 patients, 10,8 % des patients tuberculeux avaient des granulomes epithelioides sans necrose caseeuse sur leur BGSA, independamment de la localisation de la tuberculose, du statut VIH du patient ou du caractere bacillifere de l’infection. Conclusion La presence de granulomes epithelioides a la BGSA ne permet donc pas d’eliminer une maladie tuberculose lorsque le clinicien hesite entre cette affection et une sarcoidose.

BACKGROUND Chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection is frequent in HIV-infected persons but their impact on pregnant HIV-infected women is understudied. We explored whether these coinfections are associated with adverse pregnancy outcomes and lower response to antiretroviral therapy (ART). METHODS Pregnancies in HIV-1-infected women included in the ANRS French Perinatal Cohort between 2005 and 2013 were analyzed if HBV and HCV infection statuses were available. RESULTS Among 4236 women, the prevalence of HBV (HBs Ag+) and HCV (RNA+) were 6.2% (95% confidence interval: 5.4 to 6.8) and 1.7% (1.3 to 2.1), respectively. HCV coinfection was strongly associated with a history of drug use; HBV coinfection was 6 times more frequent in women born in Sub-Saharan Africa than in European France. Baseline HIV viral load, CD4 count, and HIV care during pregnancy were similar in coinfected and monoinfected HIV mothers, except that 90% of HBV/HIV women were receiving tenofovir and/or lamivudine or emtricitabine. HCV coinfection was significantly associated with cholestasis [adjusted odds ratio: 4.1 (1.5-10.8), P = 0.005], preterm delivery [3.0 (1.6-5.7), P < 0.001], lower CD4 [2.6 (1.0-6.4), P < 0.001], and detectable viral load [2.3 (1.0-5.5), P = 0.06] at the end of pregnancy. HBV coinfection was not associated with any of these outcomes. CONCLUSIONS In HIV-infected women, chronic HBV infection, mostly treated using targeted ART, had no major impact on the course of pregnancy. By contrast, chronic HCV infection was associated with a higher risk of obstetrical complications and a poorer immune-virological response to ART. It is yet unknown whether cure of HCV infection before conception can limit these adverse outcomes.

BACKGROUND & AIMS Hepatitis B Virus (HBV) DNA during chronic infection can reach levels at which mother-to-child (MTC) transmission frequently occurs despite passive-active immunization of newborns. Hepatitis D Virus (HDV) RNA can reach high levels, we assessed HBV/HDV MTC co-transmission. METHODS Monocentric retrospective study (registered in ClinicalTrials.gov (NCT02044055)), after informed consent in HBV/HDV co-infected women pregnant between 01/01/2004 and 01/01/2015 in Paris, France. The children were tested when 24 months of age or older. RESULTS Twenty-two (3%) of 742 HBV infected women, HDV co-infected, gave birth to 54 children during the study period. HBV DNA was above 5 Log10 I.U/mL in 10 pregnancies previous any treatment, with HDV RNA of less than 2.3 Log10 I.U/mL. HDV RNA was above 5 Log10 I.U/mL in eight pregnancies previous any treatment, with HBV DNA of less than 1.5 Log10 I.U/mL. Inverse patterns of HBV DNA and HDV RNA were observed in 17 of 35 (49%) pregnancies: 13 (76%) received no HBV treatment; four (24%) were treated. HBV DNA was under 5 Log10 I.U/mL in 46 of the 50 assessed women (92%) at birth. Of the 36 assessed children, given passive-active immunization, 24 (66%) were protected, 10 (28%) were neither infected nor protected, one was chronically HBV infected, and one had a past HBV infection. HDV Ab was negative in the 36 children. CONCLUSIONS These results suggest that HBV/HDV MTC co-transmission is exceptional. Studies are needed, mainly in developing countries.

International audience

The risk of vertical transmission of hepatitis B virus (HBV) increases as maternal HBV DNA increase, despite serovaccination to newborns.From 1 July 2012 to 1 January 2016, all pregnant women in Lariboisiere Hospital, Paris, France, with HBV DNA of 5 log10 IU/ml and above were administered tenofovir from week 28 of pregnancy until delivery. HBV DNA was measured at months 1, 2 of tenofovir and at delivery. The newborns were serovaccinated, tested for hepatitis B surface antigen, hepatitis B core antibody (HBcAb)±HBV DNA, and hepatitis B surface antibody (HBsAb) when aged 9 months, and then 24 months. This study was registered in http://www.ClinicalTrials.gov (NCT02039362).Thirty-one women gave birth to 37 newborns. Maternal HBV DNA at baseline was 8.23 log10 IU/ml and above in 12 pregnancies. The mean (median) HBV DNA were 4.4±1.2 (4.8), 3.3±1.7 (3.8), and 2.1±1.9 (2.0) log10 IU/ml at months 1, 2 of tenofovir and at delivery, respectively. Twenty-seven newborns were followed up: none of the 19 children aged 9 months or older was positive for hepatitis B surface antigen when aged 9 months; 14 children tested positive for HBcAb (probably transferred maternal antibodies, not found when aged 24 months) and for HBsAb without HBV DNA. Four of the 19 children showed HBsAb without HBcAb, the last being doubtful for HBcAb and HBsAb without HBV DNA. Eight newborns aged less than 9 months were not tested.Tenofovir from week 28 of pregnancy to highly viremic HBV women plus serovaccination to newborns could prevent chronic and past infection.

Objectives Previous studies in HIV-infected populations have yielded conflicting results on the effect of antiretroviral therapy (ART) on cognition. Our objective was to investigate the effect of several years of ART with stable central nervous system penetration effectiveness (CPE) score on neuropsychological performance in HIV-infected individuals. Methods We analysed a clinical cohort of HIV-infected patients who initiated ART between June 2003 and December 2006 and maintained stable CPE scores. Patients were evaluated with a short neuropsychological battery. Using linear regression, we examined the relationship between results of cognitive tests and CPE scores in all patients. Results Patients were divided into three similarly sized groups (CPE ≤ 1, CPE between 1.5 and 2.5, and CPE ≥ 2.5). We found that ART with high CPE scores was associated with poorer executive performances in HIV-1-infected patients. Conclusion These results suggest that cognitive performance in treated HIV-infected patients could be influenced by ART.

Introduction Les determinants de l’attrition chez les patients traites pour une tuberculose (TB) maladie sont mal connus. L’objectif de ce travail est de determiner, a partir d’une definition internationale, la prevalence et les facteurs associes a l’attrition chez les patients atteints de TB maladie ayant debute un traitement antituberculeux. Materiels et methodes Etude de cohorte observationnelle retrospective bi-centrique realisee chez des patients âges de plus de 18 ans, atteints de tuberculose maladie non multi-resistante, ayant debute un traitement antituberculeux entre le 1 er juillet 2012 et le 30 juin 2014. L’attrition est definie selon les recommandations de l’Organisation mondiale de la sante par la survenue d’une interruption du traitement antituberculeux pendant au moins 2 mois consecutifs. Les parametres socio-demographiques, ainsi que les donnees concernant les comorbidites, les caracteristiques de la TB, le suivi medical/therapeutique et l’issue du traitement ont ete recueillis. Resultats Au total, 252 patients ont ete inclus. L’âge median etait de 36,4 ans (ecart interquartile [EIQ] 29,5–50,5) et le sex-ratio (F:H) de 0,3. Les patients etaient d’origine europeenne dans 16,4 % des cas (41 patients), atteints de tuberculose pulmonaire dans 73,8 % des cas (186 patients) et etaient co-infectes par le VIH dans 11 % des cas (27 patients). L’attrition est survenue chez 38 patients (15,1 %) avec un delai median de 106 jours (EIQ 58,5–138,25). Parmi les patients perdus de vue, 84,2 % (32 patients) etaient des hommes et 78,9 % (30 patients) avaient moins de 50 ans. Les facteurs associes a l’attrition en analyse multivariee etaient la prise associee de corticoides (HR = 0,6, IC 95 % 0,4–0,9 ; p = 0,01), l’origine non-europeenne comme facteurs protecteurs (Afrique : HR = 0,4, IC 95 % 0,3–0,6 ; Asie : HR = 0,5, IC 95 % 0,3–0,8 ; Moyen-Orient : HR = 0,3, IC 95 % 0,1–0,9 ; Amerique : HR = 0,4, IC 95 % 0,2–0,9 ; p = 0,001) et la presence d’un diabete comme facteur de risque (HR = 2, IC 95 % 1,2–3,5 ; p = 0,01). Conclusion Les resultats de cette etude laissent a penser que l’attrition chez les patients atteints de TB maladie reste frequente. Les facteurs tels que l’origine des patients (i.e. : origine europeenne) et la presence d’un diabete pourraient etre retenus pour identifier les patients a risque devant beneficier de mesures specifiques pour ameliorer l’observance. Ces donnees restent a confirmer dans une etude prospective, a plus grande echelle.

Background Controlling prekallikrein activation by C1 inhibitor (C1Inh) represents the most essential mechanism for angioedema patient protection. C1Inh function in the plasma is usually measured based on the residual activity of the C1s protease not involved in the pathological process. We have hereby proposed an alternative enzymatic measurement of C1Inh function based on contact-phase activation and correlation with angioedema diagnostic requirements. Methods The contact phase was reconstituted using the purified components, with C1Inh standard or plasma sample. The kinetics of the amidase activity were monitored using Pro-Phe-Arg-pNA, independently of alpha2-macroglobulin. We prevented any interference from a possible high plasma kininogenase activity by preincubating the samples with protease inhibitor. Receiver operating characteristics (ROC) were used to calculate the assay's diagnostic performance. Results The calibration curve was built using C1Inh standard (threshold limit 0.10 × 10−3 U, i.e., 0.2 pmol), and C1Inh function was quantified in the sample, with a reference interval established based on healthy individuals (n = 281; men: 0.61–1.10 U/ml, median: 0.85 U/ml; women: 0.42–1.08 U/ml, median: 0.74 U/ml). The median values of female donors were lower than those of the others due to estrogen, yet C1Inh function remained within the reference interval. The ROC curve calculation provided the following optimum diagnostic cutoff values: women 0.36 U/ml (area under curve [AUC]: 0.99; sensitivity: 93.48%; specificity: 99.37%); and men 0.61 U/ml (AUC: 1; sensitivity: 100.0%; specificity: 100.0%). Conclusion The performance outcome provided features suitable for angioedema diagnostic or follow-up. Established by means of the kinin formation process, this assay should be preferred over the method based on a C1s protease target.

Au printemps 1988, le Département de Génétique Animale de l’Inra avait organisé un séminaire interne consacré aux «bases techniques et approches de la génétique moléculaire». Cette discipline commençait alors à émerger. La PCR (Polymerase Chain Reaction), que l’on peut qualifier de technique de base de la génétique moléculaire, venait tout juste d’être mise au point. Les cartes génétiques des espèces animales d’intérêt agronomique étaient à peine ébauchées (au plus quelques dizaines de gènes localisés sur le génome) et les premiers polymorphismes de l’ADN venaient d’être décelés. En une dizaine d’années, de discipline émergente, la génétique moléculaire est devenue une discipline en plein essor. Et pour faire le point des nouveaux acquis, très nombreux et d’intérêt potentiel majeur pour des applications aux programmes d’amélioration génétique, le Département de Génétique Animale a organisé en septembre 1999 un nouveau séminaire consacré à la génétique moléculaire. Ce séminaire de cinq jours a été particulièrement dense, à la mesure des avancées considérables réalisées récemment dans la connaissance des génomes des animaux de ferme. La qualité de l’organisation pilotée par Christelle Gérardin et Pierrette Gillet, avec l’aide efficace de Françoise Bouchain, Annie Pech, Hervé Lagant et Serge Tignoux, a contribué fortement à sa réussite. Comme il l’avait fait en 1992 à l’occasion d’un précédent séminaire intitulé «Eléments de génétique quantitative et application aux populations animales», le Département de Génétique Animale a souhaité mettre à la disposition du plus grand nombre, notamment ses partenaires professionnels et ses collègues de l’enseignement, l’ensemble des informations présentées lors de son dernier séminaire interne. Ce numéro hors série de la revue Productions Animales répond à ce souhait. Il s’intitule «Génétique moléculaire : principes et application aux populations animales» et comprend sept grands chapitres : les notions de base, les polymorphismes génétiques, la cartographie des génomes, la recherche de gènes associés à des fonctions, la transgenèse, la bioinformatique et l’utilisation des marqueurs génétiques. En une quarantaine d’articles, les chercheurs du Département se sont efforcés de faire une mise au point aussi exhaustive que possible sur l’état des connaissances dans les domaines concernés, tout en veillant à donner une place importante aux applications que l’on peut attendre à court et moyen terme de ce nouveau savoir sur les génomes et des nouveaux savoir-faire qui en résultent. Cet ouvrage n’aurait pas vu le jour sans la qualité du travail fourni par les différents intervenants et leurs secrétariats (avec une mention spéciale à Pierrette Gillet et son équipe pour la gestion informatisée de l’ensemble des contributions), l’appui opérationnel apporté par Inra Editions et le précieux concours de la rédaction de la revue Productions Animales, notamment Marie-Hélène Farce et Jean- Marc Perez, respectivement responsable de la rédaction et directeur scientifique de la revue. Les membres du comité scientifique d’organisation du séminaire (Alain Ducos, Pascale Le Roy, Eduardo Manfredi, Marie-Hélène Pinard-van der Laan, Claire Rogel-Gaillard, Daniel Vaiman et Martine Yerle) ont apporté une contribution majeure à la programmation du séminaire et ils ont également assuré, avec l’aide de Ginette Dambrine et Hubert de Rochambeau, la relecture des manuscrits. Que toutes les personnes qui, à un moment ou un autre, ont participé à l’organisation du séminaire et à la genèse de cet ouvrage collectif soient ici sincèrement remerciées. Bernard BibéChef du Département de Génétique Animale de l’InraPhilippe Mulsant et Pierre SellierCo-animateurs du comité scientifique d’organisation du séminaire

The existence of a history of myocardial infarction (MI) in patients with angina pectoris is frequently associated with certain patient characteristics, including an established history of coronary artery disease (CAD), depressed left ventricular function in some patients and multivessel coronary disease. Angina is a symptom which reveals the persistence or recurrence of myocardial ischaemia. It is uncertain whether persistent myocardial ischaemia after MI is an adverse prognostic factor. In fact, the most important known prognostic factor is left ventricular function. Before choosing an anti-anginal therapy in patients with a history of MI, coronary angiography should be performed in order to investigate the possibility of left main or multivessel CAD. Angina patients with impaired left ventricular function may benefit from revascularization but the prognostic value of percutaneous transluminal coronary angioplasty in these patients remains to be assessed. Medical anti-anginal therapy for symptoms, added to routine background treatment, is indicated when the results of revascularization are unsatisfactory or if there is an absence of indication, or a contra-indication, for revascularization procedures. Particular attention should be paid to the possible additive negative inotropic or chronotropic effects of β-blockers and certain calcium antagonists on the myocardium ( Eur Heart J 1996; 17 (Suppl G ): 25–29)

Introduction L’esperance de vie des patients vivant avec le VIH (PVVIH) s’est considerablement allongee ces 20 dernieres annees grâce aux progres du traitement antiretroviral (ARV), lui permettant d’atteindre celle de la population generale. L’efficacite therapeutique est donc un enjeu majeur. Patients et methodes Nous avons realise une etude retrospective d’une population de PVVIH sous ARV suivie dans un service de medecine interne entre 2007 et 2014. L’efficacite therapeutique a ete evaluee suivant differents schemas therapeutiques. Celle-ci etait consideree satisfaisante lorsque la charge virale etait inferieure a 50/mm3 a 6 mois de traitement. Seuls les patients en 1re ou 2e ligne de traitement ont ete inclus pour exclure le risque de resistance virologique. Les 3 schemas therapeutiques evalues etaient : 1 comprime en 1 prise par jour (groupe A), plusieurs comprimes en une prise par jour (groupe B), plusieurs comprimes en plusieurs prises par jour (groupe C). Resultats Trois cent quarante-quatre patients ont ete inclus (243 en 1re ligne de traitement, 101 en 2e ligne). Le groupe A comptait 90 patients, le groupe B, 207 patients et le groupe C, 47 patients. Les 3 groupes etaient significativement differents en termes d’origine geographique, de mode de transmission et de Nadir moyen de CD4 avant traitement. L’efficacite therapeutique de la population generale etait de 87,5 % et respectivement de 95,6 %, 83,6 % et 89,4 % pour les groupes A, B et C. L’efficacite therapeutique etait significativement differente entre les groupes A et B (p = 0,0041) mais pas entre les groupes A–C et B–C. Ces resultats restaient identiques, que les patients soient en 1re ou 2e ligne de traitement. Conclusion Notre etude montre qu’une meilleure efficacite therapeutique n’est pas uniquement correlee a une baisse du nombre de comprimes ou de prises quotidiennes. Cela laisse supposer qu’elle est aussi liee aux specificites comportementales de la population traitee.

Previous studies in HIV-infected populations have yielded conflicting results on the effect of antiretroviral therapy (ART) on cognition. Our objective was to investigate the effect of several years of ART with stable central nervous system penetration effectiveness (CPE) score on neuropsychological performance in HIV-infected individuals.We analysed a clinical cohort of HIV-infected patients who initiated ART between June 2003 and December 2006 and maintained stable CPE scores. Patients were evaluated with a short neuropsychological battery. Using linear regression, we examined the relationship between results of cognitive tests and CPE scores in all patients.Patients were divided into three similarly sized groups (CPE ≤ 1, CPE between 1.5 and 2.5, and CPE ≥ 2.5). We found that ART with high CPE scores was associated with poorer executive performances in HIV-1-infected patients.These results suggest that cognitive performance in treated HIV-infected patients could be influenced by ART.

Data were collected in the course of a divergent selection experiment for residual feed intake (RFI) of Large White growing pigs. This data set was used to estimate (i) heritability for RFI and genetic correlations of RFI with growth and carcass traits within the three sexes (male, castrate and female) and (ii) genetic correlations between sexes for these traits. Individual feed intake of animals raised in collective pens was measured by single-place electronic feeders on 1121 males (candidates for selection), 508 females and 535 castrates (sibs of candidates). Variance components were estimated using the REML methodology applied to a multitrait animal model. Estimates of heritability for RFI were 0.16 ± 0.04, 0.16 ± 0.08 and 0.23 ± 0.10 for males, females and castrates, respectively. Estimates of genetic correlations between sexes for homologous traits were not significantly different from 1 (0.88 to 0.99 for RFI, 0.79 to 0.99 for growth traits and 0.65 to 0.99 for carcass composition traits). The relatively low genetic correlations between castrates and males or females for backfat thickness (0.65 and 0.69, respectively) suggest the presence of genotype by sex interactions for this trait.

The feeding behaviour of group housed growing pigs was studied using data recorded with electronic feed dispensers “ACEMA 48”. Data were collected in 42 pens of 9 to 14 pigs, either boars or castrated males of Large White and French Landrace breeds raised from 35 to 95 or 100 kg liveweight. All the visits performed by the pigs were recorded and then grouped into meals. Differences between breeds especially concerned feeding pattern, Large White pigs performing twice as many visits per day as French Landrace pigs, but daily feed intake was the same in the two breeds under both housing type conditions (single breed or mixed breeds). In contrast, castrated males ate 17% more per day than boars. Evolution of feeding behaviour throughout the growth period showed a continuous decrease of the number of meals per day (from 7.2 in week 2 to 5.3 in week 10) and an increase of rate of feed intake, independent of breed or sex. In addition, evolutions were parallel in the two breeds, meaning that feeding behaviour for each breed was acquired early and did not evolve afterwards. Among all studied behavioural criteria, only daily feed intake was noticeably correlated with growth performance and ultrasonic backfat thickness.

This paper is a review of current knowledge about genetic effects on technological and eating qualities of pork. These effects have been recognized as primordial sources of variation of meat quality in the porcine species. Nevertheless, some significant advances have recently been obtained in this area. This literature survey reveals that: The halothane sensitivity gene (HALn) explains to a large extent the overall genetic variation in technological quality and eating quality of pork. Evidence is accumulating that the halothane sensitivity gene is not completely recessive regarding its effects on quality traits. Producing slaughter pigs heterozygous at the HAL locus may result in deficiencies in meat quality, probably depending on slaughter conditions and perhaps also on slaughter weight. Breed differences in technological and sensory qualities of pork partly result from the large breed variation in incidence of halothane sensitivity, but other factors are implied, particularly ultimate pH and intramuscular fat content of meat. The major dominant gene RN-is probably at the origin of the previously described “Hampshire effect” on meat quality. Heritability of most traits referring to the technological quality of meat is low to moderate (0.15 to 0.30), whereas heritability of intramuscular fat content is high (0.40 to 0.50). A genetic antagonism exists between technological quality of pork and growth or body composition traits. The halothane sensitivity gene is the major factor responsible for the “meat quantity — meat quality” genetic antagonism.

BK-virus is a very common polyomavirus in the global population, similar to the JC-virus responsible for Progressive Multifocal Leukoencephalopathy. BK-virus infections are an important diagnostic and therapeutic challenge in immuno-compromised patients, including: bone marrow transplant pediatric recipients in whom it may cause hemorrhagic cystitis, renal transplant recipients in whom it may cause interstitial nephropathy leading to graft loss, and in HIV infected patients in whom it may cause some types of encephalitis. Indeed, this poorly documented virus is responsible for infections with various clinical profiles, probably under-diagnosed, but could also be involved in the genesis of some cancers, especially cervix and prostate cancer. We reviewed the latest published data on this virus focusing on its possible pro-oncogenic properties. We also listed the diseases in which it is involved, with an emphasis on rare and insufficiently investigated entities. Finally, we studied the new tools available for diagnosis and treatment, and their importance in current practice.

Residual feed intake (RFI) has been explored as an alternative selection criterion to feed conversion ratio to capture the fraction of feed intake not explained by expected production and maintenance requirements. Selection experiments have found that low RFI in the growing pig is genetically correlated with reduced fatness and feed intake. Selection for feed conversion ratio also reduces sow appetite and fatness, which, together with increased prolificacy, has been seen as a hindrance for sow lifetime performance. The aims of our study were to derive equations for sow RFI during lactation (SRFI) and to evaluate the effect of selection for RFI during growth on sow traits during lactation. Data were obtained on 2 divergent lines selected for 7 generations for low and high RFI during growth in purebred Large Whites. The RFI was measured on candidates for selection (1,065 pigs), and sow performance data were available for 480 sows having from 1 to 3 parities (1,071 parities). Traits measured were sow daily feed intake (SDFI); sow BW and body composition before farrowing and at weaning (28.4 ± 1.7d); number of piglets born total, born alive, and surviving at weaning; and litter weight, average piglet BW, and within-litter SD of piglet BW at birth, 21 d of age (when creep feeding was available), and weaning. Sow RFI was defined as the difference between observed SDFI and SDFI predicted for sow maintenance and production. Daily production requirements were quantified by litter size and daily litter BW gain as well as daily changes in sow body reserves. The SRFI represented 24% of the phenotypic variability of SDFI. Heritability estimates for RFI and SRFI were both 0.14. The genetic correlation between RFI and SRFI was 0.29 ± 0.23. Genetic correlations of RFI with sow traits were low to moderate, consistent with responses to selection; selection for low RFI during growth reduced SDFI and increased number of piglets and litter growth, but also increased mobilization of body reserves. No effect on rebreeding performance was found. Metabolic changes previously observed during growth in response to selection might explain part of the better efficiency of the low-RFI sows, decreasing basal metabolism and favoring rapid allocation of resources to lactation. We propose to consider SRFI as an alternative to SDFI to select for efficient sows with reduced input demands during lactation.

Residual feed intake (RFI) is defined as the difference between the observed feed intake and that expected based on requirements for maintenance and production. A divergent selection was conducted during 4 generations in Large White male pigs to produce low and high RFI lines. The present study aims at determining the influence of this selection on biochemical and histological traits of skeletal muscle, and relating these changes to correlated effects on growth, carcass composition, and meat quality traits. At 8 d preslaughter, biopsies from the LM were taken in the fed state on 14 females from each RFI line fed ad libitum. Animals were slaughtered at 107.8 ± 8.0 kg of BW without any previous fasting. Samples of LM, semimembranosus (SM), biceps femoris (BFM), and rhomboideus muscles were taken at both 30 min and 24 h postmortem. Myofiber typing was only assessed in LM. Low RFI pigs ("efficient") had leaner carcasses with greater muscle content (P0.001), less backfat thickness (P0.001), and less intramuscular fat content in all 4 muscles (P0.01 to P = 0.04). Their greater muscle content was associated with hypertrophy of all fast-twitch fibers. Glycogen content in all glycolytic muscles (i.e., LM, SM and BFM), was greater in low than high RFI pigs. The greater accumulation of glycogen in LM of low RFI pigs was specifically located in the fast-twitch glycolytic IIBW fibers, which correspond to fibers containing IIb, IIb + IIx, or IIx myosin heavy chains. The difference in muscle glycogen content between RFI line pigs was more significant in the living animals (P = 0.0003) than at 30 min postmortem (P = 0.08). This was associated with a decreased ultimate pH (P = 0.001), and greater lightness of color (P = 0.002) and drip loss (P = 0.04) in LM of low than high RFI line pigs, suggesting that selection for reduced RFI may impair some meat quality traits, such as water-holding capacity. Pigs from the low RFI line exhibited a greater (P = 0.02) percentage of IIBW fibers in LM and tended (P0.10) to have less lipid β-oxidative capacity in LM, SM, and BFM. In contrast, no difference (P0.10) between lines was found for citrate synthase and lactate dehydrogenase activities, mitochondrial activity, and expression of genes coding for uncoupling proteins 2 and 3. Differences between RFI pigs in plasma leptin, cortisol, and thyroid hormone concentrations are presented and discussed. In conclusion, selection for low RFI influenced muscle properties in a way favoring muscle mass, but likely impairing meat quality.

Genetic selection on residual feed intake (RFI) can be used as an alternative method to G:F to improve feed efficiency in pigs. The objective of this study was to determine the effects of selection for RFI on digestive and metabolic utilization of energy in 2 lines of purebred French Large White castrated male pigs obtained from a divergent selection experiment over 6 generations. The RFI(+) (high RFI) line consumed more feed than predicted from performance compared with the RFI(-) (low RFI) line. Digestibility of energy and nutrients, total heat production (HP), HP related to physical activity, and energy and N balance were measured in respiration chambers for a 6-d period in pigs offered feed ad libitum. Pigs remained in the chamber for an additional day and did not receive any feed to estimate the fasting HP and calculate the thermic effect of feeding. Five pairs of 2 littermates from the same farrowing batch were used in each line. Because 2 respiration chambers were available for the trial, pigs were measured regularly during the 25- to 95-kg growing period. Two pigs per chamber were used until pigs reached 45 kg of BW, and 1 pig per chamber was used thereafter. Individual feed intake and BW gain were measured continuously from weaning to the end of the trial. Pigs were fed 3 diets with decreasing CP contents during the 25 to 45 (period 1), 45 to 65 (period 2), and 65 to 95 (period 3) kg of BW periods. Average daily feed intake was greater in RFI(+) pigs than in RFI(-) pigs between 25 and 65 kg of BW (2,128 vs. 1,891 g/d; P0.01) and G:F was 8% greater in RFI(-) pigs compared with RFI(+) pigs (P0.01). There was no line effect on digestibility coefficients or N retention, irrespective of the experimental period studied. Nitrogen retention was 31.2, 28.7, and 20.8 g/d at periods 1, 2, and 3, respectively (P0.001). The HP was greater in RFI(+) pigs than in RFI(-) pigs (1,497 vs. 1,383 kJ.kg of BW(-0.60).d(-1); P0.01), with no subsequent line effect on energy retention. The activity-related HP tended to be greater in RFI(+) pigs than in RFI(-) pigs (250 vs. 218 kJ.kg of BW(-0.60).d(-1); P = 0.09), and the fasting HP was 10% greater (P = 0.04) in RFI(+) pigs than in RFI(-) pigs (846 vs. 771 kJ.kg of BW(-0.60).d(-1)). The thermic effect of feeding, expressed as a percentage of ME intake, was the same for both lines of pigs (average, 14.7%). In conclusion, the RFI(+) pigs are energetically less efficient because of their greater HP related to physical activity and basal metabolic rate.

Introduction La tuberculose est une maladie a declaration obligatoire en France depuis 1964. La mise en place d’infrastructures chargees de surveiller et de lutter contre cette pathologie (institut de veille sanitaire, comite de lutte antituberculeuse…) a permis une nette diminution de son incidence. Ainsi, le nombre de cas de tuberculose-maladie et de deces lies a la tuberculose ont chute par rapport aux annees 1990 : 16,5 cas declares/100 000 habitants en 1993 contre 7,5/100 000 en 2012. Depuis 2010, il semble se dessiner une certaine stabilite avec environ 5000 cas declares par an. En 2012, l’Ile de France representait 35 % des nouveaux cas declares en France. Regulierement confrontes a cette pathologie dans notre pratique quotidienne, nous nous sommes interesses aux donnees epidemiologiques de notre centre. Patients et methodes Recueil retrospectif, descriptif, monocentrique s’etendant du 01/01/2004 au 31/07/2014 des patients diagnostiques et/ou suivis pour une tuberculose (pulmonaire ou extra-pulmonaire), certaine ou probable, dans un service de medecine interne d’un CHU parisien. Resultats Cinq cent soixante-quinze cas de tuberculoses, toutes localisations confondues, ont ete diagnostiquees et/ou suivies dans le service. Cent soixante-deux cas concernaient des femmes (28 %). La moyenne d’âge etait de 39,7 ans. Parmi les patients, 19,5 % etaient infectes par le VIX, 43,6 % des patients venaient d’Afrique subsaharienne, 14,4 % d’Afrique du Nord, 7,6 % d’Europe (hors France), 12,5 % de France, 19,1 % d’Asie et 2,6 % d’Amerique du Sud et Caraibes. Cinquante-quatre etaient des rechutes (9,3 %). Le nombre de cas par an ne variait pas significativement dans le temps avec une moyenne de 54 patients par an. Deux cent trente-neuf cas (41,5 %) etaient atteints de tuberculoses parenchymateuses pulmonaires pures sans localisation extra pulmonaire retrouvees. Parmi eux, 71 % etaient bacilliferes. Cent quatre patients presentaient a la fois une tuberculose pulmonaire et extrapulmonaire : 38,5 % etaient bacilliferes. Quarante-cinq pour cent d’entre eux avaient une atteinte ganglionnaire, 14 % une atteinte du systeme nerveux central et 9,6 % une atteinte osteoarticulaire. Les 222 atteintes extrapulmonaires pures se repartissaient en 49,5 % d’atteintes ganglionnaires, 13,9 % d’atteintes pleurales, 11,3 % d’atteintes osteoarticulaires, 7,2 % d’atteintes du systeme nerveux central, 13,5 % d’atteintes abdominales. Enfin, on retrouvait 10 cas de pericardites, 13 abces cutanes ou profonds et des hemocultures positives chez 4 patients (0,7 %). La repartition des differentes localisations de la tuberculose etait stable au cours du temps (p = 0,68). Soixante-cinq cultures presentaient au moins une resistance aux antituberculeux dont 44 (7,6 %) aux anti-tuberculeux majeurs (rifampicine ou isoniazide). Trois cent quarante-sept patients (60,3 %) ont ete entierement traites dans notre centre, 18 patients sont decedes au cours du suivi dont 8 de la tuberculose. Soixante-quatre patients ont ete perdus de vue ou n’ont pas recu de traitement (fugue ou problemes de compliance). Discussion Le nombre de diagnostic de tuberculose dans les quartiers draines par notre centre hospitalier, ou reside un nombre important de migrants en grande precarite, semble donc rester stable depuis dix ans alors que la tendance est a la baisse au niveau national. De plus, la proportion de tuberculose bacillifere semble nettement plus importante dans notre cohorte (61,2 %) que celle rapportee par l’INVS au niveau national en 2012 (46,1 %) (p Conclusion La lutte contre la tuberculose reste une priorite de sante publique, surtout pour les populations en grande precarite concentrees dans le nord parisien et le departement 93.

We describe a case of recurrent Scopulariopsis brevicaulis subcutaneous infection, which occurred 6 years after the patient underwent liver transplantation. Combined surgery and long-term oral therapy with terbinafine resulted in a favorable outcome, although this is not the rule in the previously reported S. brevicaulis infections in immunocompromised patients.

4/8 (50%) rapidly developed lamivudine-resistance mutations. Patients with HBV-reactivation were characterized by a degree of HBsAg-variability higher than that in stably-HBV-infected patients, particularly in a-determinant critical for modulating HBVinfectivity and evasion from neutralizing-antibodies (mean geneticdivergence: 0.058 versus 0.017, P < 0.001). Furthermore, both the percentage of patients with at least 1 immune-escape mutation, and the median number of immune-escape mutations in a-determinant, were significantly higher in patients with HBV-reactivation than in controls (64.3%[9/14] versus 27%[27/100], P = 0.008; and 1[IQR: 0–2] versus 0[IQR: 0–2], P = 0.002, respectively). Moreover, ≥1 specific HBsAg-mutation (M103I-T123N-S143L-D144E-S154L-V190A) was present in 8/14 (57.1%) patients with HBV-reactivation status (independently from the presence of drug-resistance mutations), while in controls they were absent (0/100 for M103I-T123ND144E-S154L), or nearly absent (1/100 for S143L and 2/100 for V190A). All the identified mutations (except for V190A, situated in the membrane-embedded C-terminal domain) are localized in a-determinant, and are known to be associated with decreased HBsAg-antigenicity. T123N introduces an N-linked glycosylationsite, thus potentially reducing HBsAg immunogenic-surface. Conclusions: HBV-reactivation correlates with an increased HBV ability to evade the pressure imposed by humoral immuneresponse. This highlights the need of a careful monitoring, and of establishing an adequate, high-genetic-barrier therapy (if required) in order to prevent HBV-reactivation and consequent liver damage in the setting of immune-suppression.

The comparison of the anti-ischemic activity of trimetazidine and propranolol was evaluated by multiple end points (clinical, exercise test, and ambulatory electrocardiogram [EGG] monitoring criteria) in 149 male patients with effort angina who received either trimetazidine 20 mg tid or propranolol 40 mg tid during a period of 3 months. The distribution of the standardized differences between the two treatments for each variable was obtained by a permutation method. The medians (estimation of the actual difference between the two treatments) and the 5, 25, 75 and 95% quantiles were represented on the same diagram for all end points. The pattern of the standardized distribution of the differences showed a similar activity of both drugs on symptoms and nitrates consumption, on exercise tolerance and increase in ischemic threshold at exercise, and on ischemia recorded at ambulatory ECG monitoring. Conversely, only propranolol decreased heart rate and rate pressure product at rest as well as at exercise, underlining the difference in the mode of action of the two drugs. This descriptive technique is an attractive method to evaluate the differences between drugs considering multiple criteria favouring the estimation of these differences together with their variability.

Trimetazidine has been shown to improve anginal symptoms and exercise tolerance in patients with coronary artery disease (CAD). To determine the hemodynamic effects of trimetazidine, systemic hemodynamics were studied in 15 patients suffering from CAD (12 male, 3 female, mean age +/- SEM = 58.6 +/- 1.8 years). Cardiac index was determined by thermodilution method. Left ventricular and aortic pressures were measured using micromanometers (Miller Instruments). After basal measurements, patients were randomly given either placebo (n = 5) or one of two therapeutic doses of trimetazidine 1 mg.kg-1 (n = 5) or trimetazidine 1.5 mg.kg-1 (n = 5) in a double-blind procedure. Data were recorded 5, 10 and 20 min after intravenous drug bolus. Throughout the procedure, the evolution of systemic hemodynamic parameters was not statistically different between the three groups, in particular heart rate, cardiac index, systolic, diastolic and mean aortic pressures, end-diastolic ventricular pressure, mean capillary wedge pressure, pulmonary artery pressures or systemic vascular resistances. We conclude that, unlike other antianginal drugs (particularly beta-blockers, nitrates and calcium-channel inhibitors), trimetazidine does not modify systemic hemodynamics in patients with CAD. These results are consistent with a direct effect of trimetazidine on the ischemic myocardial cell previously reported.

Objectifs Comprendre le debord meniscal observe en IRM sur les coupes frontales en relation avec les fissurations radiaires du menisque ou les lesions transfixiantes des attaches meniscales. Interpreter ce debord meniscal en fonction d’une comprehension des fibres principales constitutives du menisque en continuite avec les attaches meniscales, le ligament intermeniscal et le ligament menisco-femoral (lasso). Materiels et methodes Etude de 55 IRM avec des lesions caracteristiques de ruptures radiaires ou de rupture de l’attache meniscal posterieure. Correlation avec le debord meniscal visible sur les sequences frontales d’IRM. Interpretation en fonction de l’hypothese d’une continuite des fibres meniscales longitudinales avec les racines meniscales et aussi avec le ligament intermeniscal et le ligament menisco-femoral. Ces differentes fibres constituant une continuite ligamentaire ou tendineuse enserrant la base des condyles et parfaitement adaptee sur les plateaux tibiaux. Resultats Correlation avec le debord meniscal visible sur les sequences frontales d’IRM. Interpretation en fonction de l’hypothese d’une continuite des fibres meniscales longitudinales avec les racines meniscales et aussi avec le ligament inter-meniscal et le ligament menisco-femoral. Ces differentes fibres constituant une continuite ligamentaire ou tendineuse enserrant la base des condyles et parfaitement adaptee sur les plateaux tibiaux. Conclusion Il apparait que le debord meniscal est un signe tres significatif de la discontinuite du lasso meniscal. Ce signe doit faire rechercher systematiquement une rupture radiaire du menisque ou une desinsertion des attaches posterieures.