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RationaleAortic valve stenosis (AVS) is a major contributor to cardiovascular death in the elderly population worldwide. MicroRNAs (miRNAs) are highly dysregulated in patients with AVS undergoing surgical aortic valve replacement (SAVR). However, miRNA-dependent mechanisms regulating inflammation and calcification or miRNA-mediated cell-cell crossstalk during the pathogenesis of AVS are still poorly understood. Here, we explored the role of extracellular vesicles (EV)-associatedmiR-145-5p, which we showed to be highly upregulated upon valvular calcification in AVS in mice and humans.MethodsHuman TaqMan miRNA arrays identified dysregulated miRNAs in aortic valve tissue explants from AVS patients compared to non-calcified valvular tissue explants of patients undergoing SAVR. Echocardiographic parameters were measured in association with the quantification of dysregulated miRNAs in a murine AVS model.In vitrocalcification experiments were performed to explore the effects ofEV-miR-145-5pon calcification and crosstalk in valvular cells. To dissect molecular miRNA signatures and their effect on signaling pathways, integrated OMICS analyses were performed. RNA sequencing (RNA-seq), high-throughput transcription factor (TF) and proteome arrays showed that a number of genes, miRNAs, TFs, and proteins are crucial for calcification and apoptosis, which are involved in the pathogenesis of AVS.ResultsAmong several miRNAs dysregulated in valve explants of AVS patients,miR-145-5pwas the most highly gender-independently dysregulated miRNA (AUC, 0.780, p-value, 0.01). MiRNA arrays utilizing patient-derived- and murine aortic-stenosis samples demonstrated that the expression ofmiR-145-5pis significantly upregulated and correlates positively with cardiac function based on echocardiography.In vitroexperiments confirmed thatmiR-145-5pis encapsulated into EVs and shuttled into valvular interstitial cells. Based on the integrated OMICs results,miR-145-5pinterrelates with markers of inflammation, calcification, and apoptosis.In vitrocalcification experiments demonstrated thatmiR-145-5pregulates theALPLgene, a hallmark of calcification in vascular and valvular cells. EV-mediated shuttling ofmiR-145-5psuppressed the expression ofZEB2, a negative regulator of theALPLgene, by binding to its 3’ untranslated region to inhibit its translation, thereby diminishing the calcification of target valvular interstitial cells.ConclusionElevated levels of pro-calcific and pro-apoptotic EV-associatedmiR-145-5pcontribute to the progression of AVS via theZEB2-ALPLaxis, which could potentially be therapeutically targeted to minimize the burden of AVS.Clinical SignificanceWhat is known?Aortic valve stenosis (AVS) is the most prevalent structural heart valve disease requiring surgical or interventional valve replacement. Currently, no medical treatment option is available to slow, halt, or reverse the progression of the disease.AVS induces pressure overload on the left ventricle (LV), resulting in concentric hypertrophy and LV dysfunction.AVS is not an exclusively degenerative disease that leads to fibrosis and calcification of the valve cusps but rather a chronic inflammatory disease, in which mechanical strain and shear stress lead to endothelial dysfunction and immune cell infiltration, which induces chronic inflammation, apoptosis and differentiation of valvular interstitial cells into osteoblast-like cells.Increasing osteoblastic differentiation and the formation of macrocalcifications are hallmarks of the later stages of AVS.What is the new information we provide?During aortic valve stenosis, expression pattern of vesicle-associated regulatory miRNAs is altered.Patient-derived aortic valve tissue demonstrated an increased expression ofmiR-145-5pin humans, as well as in aortic valve explants from an experimental murine AVS model.MiR145-5pcontributes to calcification of the aortic valve through ZEB2, a transcriptional repressor of ALPL, in valvular interstitial cells.Extracellular vesicular shuttling ofmiR-145-5pcontributes to valvular cell-cell crosstalk and plays a role in the pathogenesis of AVS.

Background Aortic valve stenosis (AVS) is the most common valve disease worldwide. Thought to be a purely degenerative disease, it is now clear that shear stress/endothelial dysfunction, lipid deposition and inflammation lead to calcification and stenosis of the valve. There is evidence, that extracellular vesicles (EVs) are actively involved in calcification processes. Practically all cells, including endothelial cells, can generate EVs, which can be shed into the blood stream and into the interstitial space. EVs contain lipids, proteins and nucleic acids, including noncoding RNAs (ncRNAs). EVs can be taken up by acceptor cells and their cargo, especially the ncRNA content, can change the phenotype of these cells. NcRNAs have been shown to have protective and damaging properties in AVS, which can lead to disease progression. EVs are actively involved in atherosclerosis and vascular calcification, but their role during AVS formation remains largely unknown. Purpose We hypothesize, that EV-derived ncRNAs play a crucial role during calcification of the aortic valve through regulation of endothelial to mesenchymal transition (EndMT) and calcification of valvular interstitial cells. Methods and results In initial screening experiments, we investigated ncRNA (micro RNA, miRNA and long noncoding RNA, lncRNA) content in aortic valve tissue from explanted human aortic valves from patients undergoing surgical aortic valve replacement. There is a differential expression of miRNAs and lncRNAs in aortic valve tissue from patients with AVS and patients without AVS. We could also show a differential packaging of ncRNAs into EVs generated from patient aortic valve tissues. Furthermore, ncRNA expression in aortic valve tissue is altered in a “wire-injury” mouse model of AVS. We can demonstrate in vitro that EVs and their content can be transferred from valvular endothelial cells (VECs) to valvular interstitial cells (VICs) and vice versa. Additionally, we have established an isolation method of VECs and VICs from human samples. To identify ncRNAs involved in EndMT, we are investigating the effect of laminar and pulsatile flow on the expression of ncRNAs in vitro. We can demonstrate that different flow patterns lead to a vast change in ncRNA expression in primary VECs. Downstream effects of identified ncRNAs are currently under investigation in our in vitro calcification and EndMT models. Transfection of VICs with miRNA mimics and inhibitors and lentiviral transduction of our identified targets lead to an altered calcification potential of valve cells. Conclusion The analysis of the cell type specific expression of ncRNAs and the intercellular communication via EVs will greatly help our understanding of the pathomechanisms leading to valvular calcification. Pathway analysis will generate new targets that could be used to develop therapeutics to ameliorate disease progression. EV-based miRNA mimics and inhibitors could be used to treat valvular calcification. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Deutsche Forschungsgemeinschaft, TRR259; Else-Kröner-Fresenius

Discipline Clinique. Introduction et but de l’etude La denutrition est un veritable probleme de sante publique engendrant d’importantes complications parmi lesquelles les infections nosocomiales(IN). Neanmoins, la denutrition ne fait classiquement pas partie des facteurs de risque reconnus d’IN. L’objectif de cette etude a donc ete d’evaluer l’impact de la denutrition sur la survenue d’IN, et notamment d’estimer dans quelles proportions la denutrition pouvait etre consideree comme un facteur de risque independant d’IN. Materiel et methodes L’etude etait prospective, monocentrique, composee de patients adultes hospitalises dans 2 poles medico-chirurgicaux du CHU de Strasbourg. L’enquete s’est deroulee sur cinq semaines successives, de fevrier a mars 2017. Les patients ont beneficie d’une evaluation de l’etat nutritionnel par une dieteticienne selon les recommandations HAS 2003–2007, avec le recueil de l’IMC, la perte de poids, l’albuminemie, l’EVA des ingesta et calcul du NRI. La survenue d’une IN a ete ensuite recherchee puis validee par un medecin expert de l’Equipe operationnelle d’hygiene du CHU selon les references de l’Enquete nationale de prevalence des IN. Sur le plan statistique, les comparaisons de moyennes ont ete realisees a l’aide d’un test t ou d’une Anova selon les cas, les comparaisons des distributions des variables qualitatives par un test du Chi2 et une regression logistique utilisee pour determiner les variables predictives d’une IN. Resultats et analyse statistique Parmi les 609 patients eligibles, 339 ont beneficie d’une evaluation nutritionnelle complete. Au total, 49,9 % des patients etaient denutris avec 35,4 % et 14,5 % respectivement moderement et severement denutris. Un total de 57 patients ont presente une IN, soit une incidence de 16,8 %. Il existe une plus forte incidence des IN en fonction de la gravite de la denutrition (5,9 % non denutris vs 23,3 % moderement denutris vs 38,8 % severement denutris ; p Conclusion Au vu de nos resultats, la denutrition semble etre un facteur de risque independant et important de developpement d’une IN au meme titre qu’une duree d’hospitalisation prolongee ou la presence d’un KT central. L’impact de la denutrition sur la survenue d’une IN est amplifie par une duree d’hospitalisation qui se prolonge, ces deux elements etant souvent intriques en pratique clinique courante, avec l’aggravation de l’etat nutritionnel des patients dont l’hospitalisation se prolonge.

After a decade of constant decline, the number of syphilis cases has been steadily increasing since the 2000s, particularly in HIV infected patients. Neurosyphilis is a rare manifestation of this sexually transmitted disease for which we performed a retrospective study and analyzed clinical manifestations.We reviewed retrospectively all the neurosyphilis cases admitted to Strasbourg University Hospital between 2004 and 2014. We included and analyzed 13 patients admitted during this period who met the diagnostic criteria for neurosyphilis.Nine of 13 patients had isolated visual manifestations; three (23.1%) experienced posterior uveitis, two (15.4%), panuveitis, and 4 (30.8%) had papillitis. Out of five patients (38.5%) who were HIV positive, three (60%) had a CD4 cell count above 400/mmOphthalmologists appear as key players in the identification, management and follow-up of neurosyphilis, since ocular findings are key diagnostic features in these patients.

Papillome im Osophagus sind seltene endoskopische Befunde. Ihr Stellenwert und insbesondere ihr Malignitatspotenzial sind aktuell noch unklar. In Einzelfall-Berichten wird eine maligne Degeneration und der Nachweis Humaner Papilloma-Viren (HPV, oft der Subtypen 6, 11, 16, 18) beschrieben, wie HPV-Subtypen auch bei papillomatosen Karzinomen im Genital- und Oropharynxbereich wiederholt nachweisbar sind und als pathogenetisch -ursachlich angeschuldigt werden. Wir berichten uber einen 48-jahrigen Patienten der im distalen Osophagus/Kardiabereich eine ca. 1,5 × 2,5 cm grose, polypoide Formation (Paris Is) aufwies, die intermittierend in den Magen prolabierte und diskutieren das Krankheitsbild und die aktuelle Literatur.

Raine syndrome is an autosomal recessive disorder caused by mutations in the FAM20C gene. FAM20C codes for the human homolog of DMP4, a dentin matrix protein highly expressed in odontoblasts and moderately in bone. DMP4 is probably playing a role in the mineralization process. Since the first case reported in 1989 by Raine et al. 21 cases have been published delineating a phenotype which associates dysmorphic features, cerebral calcifications, choanal atresia or stenosis and thoracic/pulmonary hypoplasia. Kan and Kozlowski suggested the name of Raine syndrome to describe this new lethal osteosclerotic bone dysplasia. All the cases described were lethal during the neonatal period except for the last two reported patients aged 8 and 11 years who presented severe mental retardation. Here we describe two sisters, with an attenuated phenotype of Raine syndrome, who present an unexpectedly normal psychomotor development at ages 4 and 1, respectively. Identification of a homozygous mutation in the FAM20C gene confirmed the Raine syndrome diagnosis, thus contributing to the expansion of the Raine syndrome phenotype. This case report also prompted us to revisit the FAM20 gene classification and allowed us to highlight the ancestral status of Fam20C.

Summary Objective: The aim of our study was to evaluate the diagnostic contribution of 18F-fluoro-deoxyglucose (18F-FDG)-positron emission tomography (PET)/computed tomography (CT) in patients with fever of unknown origin (FUO) or unexplained prolonged inflammatory syndrome (UPIS) in real life. Patients and methods: We performed a retrospective study including 14 patients with FUO or UPIS hospitalised in our institution (Strasbourg University Hospital, France) between January 2005 and July 2006. 18F-FDG-PET/CT was considered helpful when abnormal results allowed an accurate diagnosis. Results: 18F-FDG-PET/CT was helpful in half the patients (7/14) for final diagnosis. A diagnosis was reached in 87.5% of the patients (7/8) with an abnormal 18F-FDG-PET/CT but only in 50% of the patients (3/6) with a normal 18F-FDG-PET/CT. Conventional chest and abdominal CT was performed in 13 patients before ordering 18F-FDG-PET/CT. We considered that 18F-FDG-PET/CT was essential to establish the final diagnosis in only 23% of the patients (3/13) since neither chest nor abdominal CT identified abnormalities consistent with the final diagnosis. However, among the three patients, two were diagnosed with large vessel vasculitis and one patient with local prosthetic infection. Conclusions: Our study supports the potential interest of 18F-FDG-PET/CT in the diagnostic workup of FUO and UPIS as it helped establish a fine diagnosis in half of the cases. However, 18F-FDG-PET/CT appeared to be essential to the final diagnosis in only 23% of the cases. In our opinion, this protocol should be performed as a second level test, especially when conventional CT is normal or is unable to discriminate between active and silent lesions.

The ciliopathies are an expanding group of disorders caused by mutations in genes implicated in the biogenesis and function of primary cilia. Bardet-Biedl syndrome (BBS) is a model ciliopathy characterized by progressive retinal degeneration, obesity, polydactyly, cognitive impairment, kidney anomalies and hypogonadism. Mutations in SDCCAG8(NPHP10) were described recently in patients with nephronophthisis and retinal degeneration (Senior-Loken syndrome; SLS). Given the phenotypic and genetic overlap between known ciliopathy genes, we hypothesized that mutations in SDCCAG8 might also contribute alleles to more severe, multisystemic ciliopathies. We performed genetic and phenotypic analyses of 2 independent BBS cohorts. Subsequent to mutation screening, we made a detailed phenotypic analysis of 5 families mutated for SDCCAG8 (3 homozygous and 2 compound heterozygous mutations) and conducted statistical analyses across both cohorts to examine possible phenotype-genotype correlations with mutations at this locus. All patients with mutations in SDCCAG8 fulfilled the diagnostic criteria for BBS (retinal degeneration, obesity, cognitive defects, renal failure, hypogonadism). Interestingly, none of the patients with primary SDCCAG8 mutations had polydactyly, a frequent but not obligatory BBS feature. In contrast, the same patients displayed early-onset renal failure, obesity, as well as recurrent pulmonary and ENT infections. Comparison of the phenotypes of these families with our entire BBS cohort indicated that renal impairment and absent polydactyly correlated significantly with causal SDCCAG8 mutations. Thus, SDCCAG8 mutations are sufficient to cause BBS in 1–2% of our combined cohorts, and define this gene as the sixteenth BBS locus (BBS16). The absence of polydactyly and the concomitant, apparently fully penetrant association with early kidney failure represents the first significant genotype-phenotype correlation in BBS that potentially represents an indicator for phenotype-driven priority screening and informs specific patient management.

Aim To study prospectively two methods for the bacteriological diagnosis of osteomyelitis related to diabetic foot ulcer: needle puncture performed across normal skin surrounding the foot ulcer and superficial swabbing of the ulcer. Patients and methods Diabetic patients with a foot ulcer complicated by bone or joint infection, as detected by X-ray imaging, were included in the study. Ulcer swabbing and needle puncture were performed in each patient. To reach the tissue nearest the bone surface, needle puncture was guided by X-ray imaging and the drop of fluid obtained by aspiration was used for both aerobic and anaerobic bacterial culture. Results Twenty-one diabetic patients were included. The mean number of microorganisms isolated by needle puncture was significantly lower compared with that obtained by superficial swabbing: 1.09 vs. 2.04 (P

Resume Introduction Une enquete prospective hospitaliere portant sur la prise en charge des dermohypodermites bacteriennes avait ete realisee avant la conference de consensus « Erysipele. Fasciite necrosante : quelle prise en charge ? ». Les resultats de cette enquete ont ete diffuses debut 2001. Afin d’evaluer l’impact eventuel des recommandations de la conference sur les pratiques hospitalieres concernant l’erysipele, nous avons realise une nouvelle enquete prospective fin 2002. Malades et methodes Le questionnaire utilise etait identique a celui de l’enquete de 2001. Il colligeait de facon anonymisee les caracteristiques cliniques, les examens complementaires realises (bacteriologiques, imagerie), le traitement initial et l’evolution. Ce questionnaire a ete adresse aux services de dermatologie, de medecine interne et/ou maladies infectieuses et d’urgences ayant repondu a la premiere enquete (n = 124). Les malades incluables dans l’etude etaient ceux hospitalises entre le 01/09/2002 et le 30/11/2002. L’analyse statistique a compare les resultats a ceux de l’enquete precedente. Resultats Les fiches de 245 malades ont ete recueillies, qui provenaient de 41 services (15 en CHU, 23 en CHG, 3 en hopital militaire) dont 235 erysipeles. Pour les erysipeles, l’âge moyen etait de 65 ± 2,5 ans, le sex ratio H/F de 0,66, et la localisation au membre inferieur dans 89,5 p. 100 des cas. Un echo-Doppler veineux des membres inferieurs etait fait dans 41 p. 100 des cas, des hemocultures dans 51 p. 100 des cas et des prelevements bacteriologiques de porte d’entree dans 33 p. 100 des cas. L’antibiotherapie initiale etait la penicilline G dans 38 p. 100 et la pristinamycine dans 18 p. 100 des cas (autre : 44 p. 100). Elle etait initialement par voie IV dans 73 p. 100 des cas. Un traitement anticoagulant etait associe dans 60 p. 100 des cas. L’evolution a ete favorable dans 94 p. 100 des cas avec une duree moyenne d’hospitalisation de 11,2 ± 1,2 jours et d’antibiotherapie de 17,7 ± 1,3 jours. Le doppler veineux et les hemocultures etaient moins frequemment pratiques qu’avant la conference de consensus, alors qu’aucune difference n’etait trouvee pour l’antibiotherapie et les traitements adjuvants. Commentaires L’enquete de suivi montre une stabilite des pratiques hospitalieres dans l’erysipele, surtout en matiere de traitement. En revanche, la tendance nette a limiter les examens complementaires est en accord avec les conclusions de la conference de consensus.

Resume Introduction Le syndrome de Cogan correspond a l’association d’une keratite interstitielle non syphilitique et d’une atteinte audio-vestibulaire a type de maladie de Meniere. Observation Un syndrome de Cogan a ete revele par une diarrhee glairo-sanglante chez une femme âgee de 21 ans ayant pour principal antecedent une maladie de Hirschsprung. L’IRM cerebrale a permis de mettre en evidence une nevrite bilaterale d’allure virale de la VIIIe paire crânienne, encore jamais decrite dans la litterature. L’evolution des atteintes visuelle et auditive fut favorable sous corticotherapie. Conclusion Le diagnostic precoce du syndrome de Cogan peut permettre une regression des symptomes visuels et surtout audio-vestibulaires sous corticotherapie.

Fluoroquinolones present various pharmacokinetic properties. That's the way we carried out a bibliographic summary about the pharmacokinetics of pefloxacin, ofloxacin and ciprofloxacin in patients hit by chronic renal failure, under haemodialysis or under continuous ambulatory peritoneal dialysis. Then, we will describe how to adapt drug dose according to the degree of renal insufficiency and the used molecule.

Resume Le nephroblastome ou tumeur de Wilms se complique parfois d’une atteinte neurologique medullaire qui temoigne de metastases spinales. Dans l’observation que nous rapportons l’atteinte medullaire s’explique differemment. Observation. – Chez un nourrisson de deux mois est mis en evidence un nephroblastome extrarenal de situation sous-renale, en sablier, responsable d’une compression medullaire epidurale. Conclusion. – Une tumeur abdominale paravertebrale en sablier peut correspondre, non a un neuroblastome, mais a un nephroblastome.

Resume En 1995, nous avons observe l'emergence d'E. aerogenes producteurs de β-lactamases a spectre etendu dans certains services de l'hopital. Objectifs – Compte tenu des enjeux therapeutiques, ecologiques et economiques importants que peuvent representer l'apparition et la diffusion des bacteries resistantes aux antibiotiques en milieu hospitalier, nous avons etudie les enterobacteries productrices de β-lactamases a spectre etendu au sein des Hopitaux Universitaires de Strasbourg. Patients et methodes – Quatre ans apres, nous avons realise une enquete epidemiologique prospective sur une periode de six mois, du 1er novembre 1998 au 31 mai 1999, en collaboration entre bacteriologistes, hygienistes, cliniciens et pharmaciens. Resultats – Cette etude met en evidence la persistance de la propagation epidemique d'un clone d'E. aerogenes au sein des Hopitaux Universitaires de Strasbourg depuis quatre ans et l'emergence de deux clones de K. pneumoniae dont la dispersion est actuellement limitee a certains services. Conclusions – Les problemes therapeutiques qui se presentent face a de tels phenomenes de resistance et les mesures qui en decoulent sont discutes.

Une serie continue de 26 enfants operes selon la technique de Duhamel pour maladie de Hirschsprung a ete soumise a une evaluation radio-clinique. A six mois et plus de la chirurgie, une opacification colo-rectale par voie basse, avec cliche de profil au remplissage, a ete realisee. Les mesures de la hauteur globale du moignon rectal (HR), de la profondeur de la partie borgne du rectum (PR), du diametre rectal (DR), du diametre de l'anastomose colorectale (DA), ont ete prises. Le volume rectal de sa partie borgne assimilee a un cylindre (VRB), le volume rectal de sa partie fonctionnelle assimilee a un cylindre (VRF), la surface de l'anastomose colo-rectale et susanale (SA), le rapport VRF/VRB, ont ete calcules a partir des mesures precedentes. Deux types de sous-groupes ont ete analyses: 1. les patients pour lesquels le moignon rectal avait ete ferme a l'aide d'une pince a suture, et ceux pour lesquels la fermeture du moignon rectal avait ete manuelle. 2. les patients n'ayant aucun trouble du transit, et ceux qui constituent un fecalome. La suture manuelle du sommet du moignon rectal (une fois sur deux) comparee a l'agrafage n'offre aucun avantage ou inconvenient (HR = 58,4 mm ±3,6 6 vs 53,9 mm ±3,7; p = 0,39. PR = 29,6 mm ±3,8 vs 24,5 mm ± 2,3; p = 0,27). Les patients constituant un fecalome (6/26) ont une HR (71 mm±1,9), une PR (36 mm±2,2) significativement plus elevees que les 20 autres patients (respectivement 51,6 mm±2,6 et 24,4 mm ±2,7; p = 0,0005; p = 0,03). La LR (30,5 mm ±2,1 vs 26,4 mm ±1,6) et le DA (31,6 mm ±1,1 vs 27,7 mm ±1,4) ne sont pas significativement differents dans les deux groupes (p=0,21; p=0,17). La SA=792 mm 2 ±59 vs 637 mm 2 ±69; p = 0,24. Le VRB (27 377 mm 3 ±5410 vs 14518 mm 3 ±3175; p=0,05) et le VRF (24038 mm 3 ±2130 vs 14759 mm 3 ±1493; p=0,004) permettent le calcul du rapport VRF/VRB. Ce dernier est proche de 1 en cas de fecalome, alors que les sujets avec un bon resultat clinique ont un rapport superieur ou egal a 2. Le lavement opaque avec cliches de profil est un procede objectif d'evaluation de l'intervention de Duhamel pour maladie de Hirschsprung. L'agrafage du sommet du moignon rectal ou sa suture manuelle ne presentent pas de difference significative. Une hauteur rectale un peu elevee peut etre compensee par une longue anastomose colo-rectale augmentant ainsi le rapport VRF/VRB.

Resume Objectif La prophylaxie de l'endocardite infectieuse, a l'occasion d'un geste a risque et chez un patient a risque (cardiopathie connue), fait l'objet en matiere d'antibioprophylaxie de recommandations dans un grand nombre de pays. L'antibiotique utilise est choisi pour etre actif sur les principaux germes causes de bacteriemie en fonction de l'acte medicochirurgical. Materiel et methodes Cette etude, realisee a partir de 66 cas d'endocardites infectieuses recenses entre 1992 et 1998 dans le service de medecine interne et des maladies infectieuses et tropicales, a permis d'evaluer l'epidemiologie de cette maladie. Resultats A l'heure actuelle, un des faits marquants est l'augmentation des infections a staphylocoques. Les protocoles d'antibioprophylaxie etablis en 1992 ne sont peut-etre plus forcement adaptes a present; en effet, ils visent essentiellement les souches de streptocoques. Commentaires Une readaptation de ces protocoles serait peut-etre utile a l'occasion d'une nouvelle conference d'experts.

Resume Objectif Nous avons voulu discuter les recommandations des mesures de prevention exposees lors de la conference de consensus par la Societe de pathologie infectieuse de langue francaise le 27 mars 1992. En effet, malgre l'utilisation des antibiotiques pour la prophylaxie de l'endocardite infectieuse, l'incidence de cette maladie n'a pas significativement diminue. Plusieurs explications peuvent etre mises en avant pour expliquer cela, par exemple: la faible observance des medecins, des dentistes et des patients; le nombre croissant de procedures medicales invasives; le risque accru d'infections par des bacteries multiresistantes; le risque d'echec, car aucune antibioprophylaxie n'est efficace a 100 %; le risque accru de toxicite et d'allergies induites par les antibiotiques. Materiel et methodes Nous avons travaille a partir d'une revue de la litterature. Resultats Les doutes concernant l'efficacite reelle de la prophylaxie des endocardites infectieuses sont toujours d'actualite. Ces reserves suggerent de concentrer les efforts et l'attention sur l'application appropriee de ces mesures dans les groupes et dans les situations les plus a risque, c'est-a-dire les patients cardiaques a haut risque (comme les porteurs de prothese valvulaire), lors des gestes buccodentaires et chirurgicaux.

To the Editors: Intravesical bacille Calmette–Guerin (BCG) therapy is an effective treatment for high-risk superficial bladder cancer. A nonspecific immune response is expected after instillation of BCG, an alive but attenuated strain of Mycobacterium bovis . Disseminated BCG disease is a rare but well known complication of this therapy. It occurs in approximately 1% of cases 1. Severe complications could occur with hepatitis and pneumonitis but bone marrow involvement is exceptional. There are limited data on factors associated with the risk of BCG infection. The role of CD4+ T-cells in controlling mycobacteria infection is well established and the susceptibility of HIV-infected individuals for tuberculosis is an argument for this 2. Nevertheless, CD8+ T-cells play a significant role in this control, in particular secreting interferon (IFN)-γ and killing infected cells given their cytotoxic potential 3. Furthermore, experimental studies have shown that CD8+ T-cells play an important role in the early control of mycobacteria infection in older mice 4, suggesting that this may be occurring in elderly people. The present study describes two disseminated BCG infections, including bone marrow involvement, in elderly patients. Severe CD8+ T-cell depletion was found in the two patients, which illustrates the importance of CD8+ T-cells in the early control of mycobacterial infection in humans. The first patient was a 74-yr-old male, admitted in our department for fever and chills. He had concomitant weight loss of 6 kg and intense fatigue over the last 15 days. 3 months earlier he had undergone a trans-urethral resection for superficial bladder cancer. Treatment was completed by weekly instillation of BCG. A few days after the second instillation, the patient noted gradual onset of fever. 3 weeks after the onset of fever, he was referred to our hospital. Clinical examination gave no conclusive results but the biological results showed elevated C-reactive protein …

Resume Des cas sporadiques d'infections a Fasciola hepatica ont ete decrits en France. Il y a environ 50 a 100 cas rapportes par an. Le traitement le plus approprie reste encore a determiner. Notre etude porte sur deux cas traites avec succes par une dose orale unique de triclabendazole (10 mg/kg). Observations cliniques Le premier cas est une femme de 35 ans, qui presente des douleurs de l'hypocondre droit associees a un syndrome febrile, avec une hypereosinophilie peu marquee, mais une seropositivite pour la distomatose, la presence de deux nodules hepatiques sur les images radiologiques et d'œufs de F. hepatica dans les selles. Le second cas est un homme de 23 ans, ayant sejourne a Madagascar un mois auparavant. L'examen clinique d'admission est normal, mais son bilan biologique presente une cytolyse hepatique importante et une serologie positive en faveur d'une distomatose hepatique. La tolerance clinique du triclabendazole pour ces deux cas a ete excellente, et les bilans de controle, deux mois apres le traitement, se sont normalises. Commentaires En se basant sur notre experience et sur les autres cas recents rapportes dans la litterature, le triclabendazole doit etre envisage comme un traitement de choix des fascioloses humaines.

The post therapeutic follow-up of Lyme borreliosis is managed according to clinical and serological data. The evolution of antibody rates is such that it doesn't constitute the best element to rely on for follow-up. Indeed, after a sometimes transitory increase of this rate during or after antibiotherapy, the decrease is very slow, sometimes several months, and often incomplete. The follow-up should thus be made according to clinical symptoms and their resolution. Resolution of some but not all symptoms must lead to discussing two options. The first is that of administrating a complementary antibiotherapy with a different mode of action than the first antibiotic used. The second is that this may be due to recontamination, especially in highly endemic zones, given that antibodies present have no protecting effect. In this case, a new antibiotherapy must of course be initiated.

Resume Le syndrome nephrotique favorise la survenue de thromboses, siegeant cependant rarement dans le territoire vasculaire cerebral. Observation. Aude, 3 ans, a presente au decours d'une rechute de syndrome nephrotique corticodependant une somnolence suivie d'une hemiparesie gauche. Le scanner cerebral confirmait l'existence d'une thrombose du sinus longitudinal superieur. L'evolution neurologique etait favorable, sans sequelles, sous traitement anticoagulant realise d'emblee par heparine de bas poids moleculaire (HBPM). Conclusion. A propos de cette observation les auteurs disculent la place des HBPM dans la prevention et le traitement des thromboses associees au syndrome nephrotique. Neanmoins, en l'absence d'etude controlees, leur utilisation doit rester prudente. heparine de bas poids moleculaire

At 28 weeks of amenorrhea, 1 fetus of a monoamniotic twin pregnancy died. Ultrasound and Doppler investigations of the surviving twin were normal. Three weeks later, endovaginal ultrasound and magnetic resonance imaging revealed massive bilateral cerebral ischemic necrosis in the surviving twin. In utero fetal blood sampling carried out before the termination did not reveal either anemia or thrombopenia. Current data suggest that cerebral or renal ischemic complications could set in immediately after the death of the first twin as a result of a period of acute hypotension. At least 2 weeks are necessary for them to be identifiable by ultrasound. It seems that they cannot be prevented by prompt delivery of the second twin.

A stereospecific high-performance liquid chromatographic method for the simultaneous determination of the four stereoisomers of 4-hydroxytertatolol, an active metabolite of tertatolol, in human and rat urine is described. The method is based on solid-phase extraction of urine followed by derivatization with S(+)-naphtylethylisocyanate. The four stereoisomers were resolved by reversed phase high-performance liquid chromatography and detected by fluorescence (λexcitation = 210 nm, no cutoff emission filter). The analytical method is suitable for the simultaneous determination of the four stereoisomers of 4-hydroxytertatolol in rat and human urine down to 22.0 ng/ml. Preliminary results in rat suggest stereoselective hydroxylation of tertatolol enantiomers.

Congenital intracranial tumors are very rare. We report an endovaginal ultrasonographic diagnosis of an anaplastic astrocytoma at 31 weeks' gestation. Other means, such as antenatal magnetic resonance imaging and fetal blood sampling were not shown to have any diagnostic advantage. A detailed literature review of the topic is provided. Copyright © 1995 International Society of Ultrasound in Obstetrics and Gynecology

Resume La maladie des legionnaires a ete une maladie longtemps meconnue en raison de la difficulte a isoler son agent causal. Legionella pneumophila , bacille a Gram negatif, occupe une place encore relativement restreinte en pathologie infectieuse tant communautaire que nosocomiale, mais il semble que son incidence soit sous estimee en raison de son polymorphisme clinique. Nous profitons de deux cas isoles de legionellose dont une forme grave diagnostiquee dans notre service pour faire une revue de la litterature concernant les manifestations extrapulmonaires de legionelloses.

Bronchopulmonary sequestration with associated non-immune hydrops has been previously reported with generally poor prognosis for the neonate. The vast majority of sequestrations are discovered postnatally, and less than half are correctly identified as sequestration before birth.Until recently, treatment for pulmonary sequestration was limited to postnatal respiratory support and resection of the sequestered lung. But aggressive respiratory support does not succeed in salvaging infants with underlying pulmonary hypoplasia. In our report, we describe the antenatal treatment of pleural effusions complicated by hydrops fetalis secondary to a bronchopulmonary sequestration, successfully managed with a transthoracic catheter placement. This therapy resulted in the resolution of pleural effusion, polyhydramnios and hydrops, with a good fetal outcome.

Summary Tularemia is an illness rare in France. This disease occurs very often after a contact with an infected hare but can also be transmitted by ticks. Ticks transmit tularemia via coxal fluid, feces and salivary injection. Six clinical types exist : ulceroglandular, glandular, oculoglandular, pharyngitis, septicemia, pulmonary, all exist when the infection is transmitted by ticks. The diagnosis is made by the isolation of Francisella tularensis or the serology. The standard treatment is based on aminoglycosides but quinolones seem to be very promising.

Resume L'infection urinaire (IU) reste un probleme majeur en pediatrie pour differentes raisons: d'une part, par sa frequence, d'autre part, par ses risques evolutifs potentiels vers l'insuffisance renale chronique en cas d'uropathie sous-jacente (cicatrices renales). La prise en charge therapeutique de l'IU chez l'enfant demeure une prescription d'antibiotiques. Le choix du schema therapeutique (1) mono- ou bitherapie, voie enterale ou parenterale, repose sur la notion de sujet a risque (enfant de moins de 18 mois) mais depend surtout de la presomption de la localisation de l'IU: haute (pyelonephrite aigue: PNA), voie parenterale et le plus souvent bitherapie au moins initiale; basse (cystite), voie enterale et monotherapie. En pratique courante, l'appreciation de la gravite et de la localisation de l'IU peut se concevoir (1) par la clinique (fievre) et la biologie (CRP > 20 mg/l). Mais cette approche non morphologique amene des erreurs d'appreciation sur la localisation (haute ou basse) et la gravite reelle (lesions presuppuratives ou suppuratives, inflammatoires ou ischemiques) de l'IU chez l'enfant. L'imagerie medicale prend (reprend) ainsi toute sa place. La tomodensitometrie (TDM) renale avec injection de produit de contraste se presente comme une exploration radiologique performante (sensibilite, fiabilite) et de realisation rapide (contexte de l'urgence diagnostique). Grâce a la meilleure localisation (haute ou basse) et la meilleure caracterisation (inflammation, ischemie, suppuration) de l'IU par l'imagerie medicale (TDM ou scintigraphie renale), les schemas therapeutiques devraient pouvoir etre adaptes, a savoir antibiotherapie exclusive ou associee a des anti-inflammatoires ou des anti-oxydants (8), avec des implications psycho-sociales et economiques (delai d'hospitalisation) et peut-etre une meilleure maitrise du risque de cicatrice renale (8). Nous envisagerons successivement l'epidemiologie, la pathogenie, le manifestations cliniques et biologiques ainsi que la place de l'imagerie medicale en presence d'une PNA chez l'enfant.

Resume Streptococcus anginosus est la seule appellation actuellement retenue dans la nomenclature internationale des Streptococcaceae . Elle doit remplacer les appellations milleri, MG, constellatus et intermedius . Cette diversite d'appellation peut s'expliquer par la diversite de cette espece quant au groupage dans la classification de Lancefield et quant au type d'hemolyse sur la gelose au sang. Le groupe F est le plus represente, puis par ordre decroissant, les groupes C, G et A. L'hemolyse gamma est la plus frequente, puis par ordre decroissant l'hemolyse beta et alpha. S. anginosus est implique dans l'infection de tous les tissus a partir d'une atteinte (traumatique ou degenerative) des muqueuses. Les infections sont caracterisees par une propension a constituer des abces (surtout hepatiques) et un polymicrobisme. La sensibilite de S. anginosus aux antibiotiques est identique a celle des streptocoques non D. Le traitement fait appel aux penicillines associees parfois aux aminosides et au drainage des abces.

HIV patients have a high rate of infectious complications. Vaccination, though less efficient in case of severe immunosuppression, can prevent some of these infections. Since 2006, new vaccine recommendations have been elaborated in France. We studied the vaccine status of HIV+ patients for influenza, Streptococcus pneumoniae, tetanus, and hepatitis A and B among an alsatian HIV+ population.From August 20, 2007 to September 15, 2007, HIV patients of the Alsace HIV center (COREVIH) were included in a prospective study, screening demographic, medical, immunovirological, and vaccination data.Three hundred and thirty-one patients were included, 49% of whom were asymptomatic, 29% symptomatic without AIDS, 18% at AIDS stage, and no documentation for 4%. Seventy-one patients (21.4%) were vaccinated against influenza, 11 (3.3%) against Streptococcus pneumoniae, 34 against HAV (only 16.3% of patients with a negative test before), 120 against HBV (60% of patients with no serological markers before), and 186 (56.2%) against tetanus. The most frequent reasons for non-vaccination were non-proposal by physicians, lack of expected effectiveness, and fear of an immunovirological adverse effect.Vaccination coverage for recommended vaccines of HIV infected people remains at a low level and appears sometimes inferior to the rates reached among the general French population. It is necessary to inform prescribers and HIV positive patients about the interest of vaccination.

Absolute differential cross sections for the photodisintegration of the deuteron at 180° for the outgoing proton have been determined at photon laboratory energies between 30 and 100 MeV. The statistical uncertainty on the individual data points is about ±4%, while the overall systematical error amounts to ±3%. The new CM frame 180° cross sections do not seem to exhibit a minimum and are in good overall agreement with the predictions from modern calculations. Between 65 and 100 MeV the mean fore-aft ratio of 1.499±0.032 was obtained in excellent agreement with modern theoretical estimates.

Absolute differential cross sections for the forward deuteron disintegration have been determined at photon laboratory energies between 20 and 100 MeV. The statistical uncertainty on the individual results is about ±2.5%, while the overall systematical error amounts to 3%; the angular resolution equals 1.5°. The new CM-frame cross sections are in fair agreement with the predictions from recent theoretical calculations.

A total of 535 chemotherapy naive, hospitalised patients (263 male/272 female) scheduled to receive cisplatin (50-120 mg m-2)-containing regimens participated in a randomised, double-blind, parallel group study to evaluate the efficacy and safety of three intravenous dose schedules of ondansetron in the prophylaxis of acute nausea and emesis. One hundred and eighty two patients received a loading dose of 8 mg of ondansetron followed by a 24 h infusion of 1 mg h-1 (group 1); 180 and 173 patients received single doses of 32 mg (group II) and 8 mg (group III) respectively, followed by a 24 h placebo infusion. Complete and major control (less than or equal to 2 emetic episodes) of acute emesis was achieved in 74% of patients in group I, 78% in group II and 74% in group III. Seventy seven per cent of the patients in group I, and 75% of patients in groups II and III respectively experienced no or mild nausea during the 24 h observation period. A retrospective stratification of the efficacy data on the basis of patient gender showed the response rate in females to be significant lower (43% vs 67%; less than 0.001). Ondanestron was well tolerated; mild headache was the most commonly reported adverse event (11% of patients) with a similar incidence in the three groups of patients. In conclusion, a single intravenous dose of 8 mg of ondansetron given prior to chemotherapy is as effective as a 32 mg daily dose given as either a single dose of a continuous infusion in the prophylaxis of acute cisplatin-induced emesis.

Resume Les salmonelloses, dont la frequence est en augmentation, se traduisent avant tout par un tableau de gastro-enterite. Neanmoins, les manifestations extra-digestives, plus rares, survenant plus volontiers chez des sujets a risque, doivent etre connues. Les tableaux cliniques realises peuvent etre multiples, fonction du site de l'infection, certains d'entre eux comme les atteintes cardiovasculaires restant particulierement graves. Le diagnostic repose toujours sur l'isolement du germe a partir du foyer infecte mais aussi frequemment des hemocultures. Au plan therapeutique, l'antibiotherapie devra etre associee dans certains cas a un geste chirurgical de drainage. Des etudes sur des series plus importantes devraient permettre de mieux preciser la place et l'interet des molecules antibiotiques plus recentes.

An outbreak of scabies occurred in the geriatric department of the Strasbourg University Hospital in September 2005. The index case presented with hyperkeratosic scabies, an extremely contagious form. The epidemic spread to several wards and pavilions and also contaminated healthcare staff and patient's families.Our objective was to describe the outbreak, its progression, and the measures taken to eradicate it.All healthcare workers, patients, and families affected in the outbreak were retrospectively studied, using medical prescriptions recorded by the hospital pharmacy, listings established by the occupational health department, and patient files.Two epidemic waves were recorded, between August 31 and December 16, 2005, affecting 51 patients and staff members in the geriatric department, with a total of 58 episodes of scabies, seven of which were recurrences. Three main measures were taken to eradicate the epidemic: setting up of "contact" isolation precautions, information for the affected individuals, and treatment of the infected patients associated to mass treatment of contact cases. The mass treatment was widely applied, involving 490 patients and 592 caregivers. All of these measures successfully curtailed the outbreak in 3 months.Rapid and radical action is essential to prevent extension of scabies within a community.

We report the case of a 27-year-old man presenting with a hepatic abscess and hereditary hemorrhagic telangiectasia (HHT). The association between HHT and an infectious disease seemed to be induced by arteriovenous malformations and maybe also by a deficit of polymorphonuclear cells, a monocyte oxidative burst and phagocytosis. This diagnosis should be suggested in case of serious infections in young patients. Prevention is based on screening for and destroying infection, antibioprophylaxis and embolization of arteriovenous malformations.

The aim of our study was to evaluate the diagnostic contribution of (18)F-fluoro-deoxyglucose ((18)F-FDG)-positron emission tomography (PET)/computed tomography (CT) in patients with fever of unknown origin (FUO) or unexplained prolonged inflammatory syndrome (UPIS) in real life.We performed a retrospective study including 14 patients with FUO or UPIS hospitalised in our institution (Strasbourg University Hospital, France) between January 2005 and July 2006. (18)F-FDG-PET/CT was considered helpful when abnormal results allowed an accurate diagnosis.(18)F-FDG-PET/CT was helpful in half the patients (7/14) for final diagnosis. A diagnosis was reached in 87.5% of the patients (7/8) with an abnormal (18)F-FDG-PET/CT but only in 50% of the patients (3/6) with a normal (18)F-FDG-PET/CT. Conventional chest and abdominal CT was performed in 13 patients before ordering (18)F-FDG-PET/CT. We considered that (18)F-FDG-PET/CT was essential to establish the final diagnosis in only 23% of the patients (3/13) since neither chest nor abdominal CT identified abnormalities consistent with the final diagnosis. However, among the three patients, two were diagnosed with large vessel vasculitis and one patient with local prosthetic infection.Our study supports the potential interest of (18)F-FDG-PET/CT in the diagnostic workup of FUO and UPIS as it helped establish a fine diagnosis in half of the cases. However, (18)F-FDG-PET/CT appeared to be essential to the final diagnosis in only 23% of the cases. In our opinion, this protocol should be performed as a second level test, especially when conventional CT is normal or is unable to discriminate between active and silent lesions.

Using non-tagged bremsstrahlung produced by a 130 MeV–20 μA c.w. electron beam of MAMI A quasi-free Compton scattering by the neutron was investigated via the 2H(γ,γ'n)1H reaction for lab scattering angles of θγ = 90° and 135°. The energy spectrum and angular distribution of recoiling neutrons were measured via time of flight and a plastic-scintillator hodoscope, respectively. Double-differential cross sections for quasi-free scattering by the neutron were determined on an absolute scale by normalizing to the Compton cross section of the proton. By comparing the experimental double-differential cross sections with predictions the electric polarizability of the neutron was determined, leading to α n = (10.7 −10.7 +3.3 ) × 10 −4 fm 3 . Thus, the upper limit of α n is further reduced as compared to our previous result, but the lower limit is still consistent with zero.

We report our experience with the endoscopic treatment of vesicoureteral reflux by a submucosal injection of Teflon in children. During a period of 20 months, 291 refluxing ureters were injected by 4 members of our surgical team. A cystography was performed 3 months later. Because 53 children have a follow-up of less than 3 months, we only consider the remaining 201 ureters. The success rate is 92% which is similar to that of surgical treatment. We insist on some precautions and contraindications. Endoscopic treatment is an undeniable progress, but surgical treatment is still required in some cases.

A first measurement of quasi-free Compton scattering by the neutron bound in the deuteron has yielded a value for the polarizability of the neutron of αn=(11.7 −11.7+4.3)×10 −4fm 3. This means that a finite value for the polarizability has been obtained, though the result is still consistent with zero. The π0 decay constant Fπ 0γγ and the pion nucleon coupling constant gNNπ have opposite signs.

Background: No consensual criteria exist to diagnose neuroborreliosis. The intrathecal anti- Borrelia antibody index (AI) is a necessary criterion to diagnose neuroborreliosis in Europe, but not in the United States. Previous studies to determine the diagnostic value of the AI found a sensitivity ranging from 55% to 80%. However, these studies included only typical clinical cases of meningitis or meningoradiculitis, and none had a control group with CSF anti- Borrelia antibodies. Methods: We studied a sample of 123 consecutive patients with clinical signs of neurologic involvement and CSF anti- Borrelia antibodies. We determined the AI for all patients and a final diagnosis was made. Patients were then divided into three groups (neuroborreliosis, possible neuroborreliosis, control). Results: Thirty of the 40 patients with neuroborreliosis had a positive AI (AI sensitivity = 75%). Two of the 74 patients with another neurologic diagnosis had a positive AI (AI specificity = 97%). Conclusion: The antibody index has a very good specificity but only moderate sensitivity. Given the lack of consensual criteria for neuroborreliosis and the absence of a “gold standard” diagnostic test, we propose pragmatic diagnostic criteria for neuroborreliosis, namely the presence of four of the following five items: no past history of neuroborreliosis, positive CSF ELISA serology, positive anti- Borrelia antibody index, favorable outcome after specific antibiotic treatment, and no differential diagnosis. These new criteria will need to be tested in a larger, prospective cohort.

This study had for aim to describe the clinical aspects and favoring factors of mucosal Leishmaniasis in an Amazonian population of 30,000 habitants in Guajara-Mirim (Rondonia-Brazil).A descriptive study was made of 16 patients with mucosal Leishmaniasis among 170 patients infected by Leishmania. Inclusion criteria were a mucosal lesion and positivity of direct microscopic examination. The patients were investigated retrospectively.Patients with mucosal Leishmaniasis were young and mostly male The absence of treatment and the number of cutaneous lesions were probably responsible for the mucosal form, as well as the host immune response and maybe, the parasite species or vector characteristics.The mucosal form of leishmaniasis affects more often young male patients and this form must be detected early to avoid destructing lesions.

Streptococcus agalactiae (Group B streptococcus) is a major cause of invasive diseases in non-pregnant adults, particularly in the elderly and those with underlying conditions. We describe these conditions and clinical characteristics of patients followed in our teaching hospital.We retrospectively reviewed clinical records of 64 patients with S. agalactiae-related invasive infection, hospitalized between January 1997 and January 2006.The mean age of patients was 59 (+/-17 years). The H:F sex ratio was 1.06. At least one underlying condition was found in 90.6%. Diabetes mellitus (43.7%), peripheral vascular disease (34.4%), myocardial ischemia (20.3%) and malignant neoplasms (20.3%) were among the most frequent conditions. The mean index of comorbidity (Charlson) was 2.5 (+/-2). Common clinical manifestations included infection of the urinary tract (32.8%), skin and soft-tissue (25%), and osteoarthritis (21.9%). Bacteremia occurred in 31.2% with no identified source in 2 patients. During the first month, 2 cases of endocarditis, 1 case of meningitis, and 4 deaths occurred.We confirm the importance of underlying diseases in the emergence of S. agalactiae infections.