Gas mixture for deep-UV plasma emission in a hollow-core photonic crystal fiber.

We report on the first deep-ultraviolet/ultraviolet (DUV/UV) emission using a highly compact microwave-driven plasma-core photonic crystal fiber. The latter consists of a few centimeter long micro-plasma column of a gas mixture in the core of Kagome hollow-core photonic crystal fiber. The plasma is generated by nonintrusively exciting a ternary gas mixture of argon, nitrogen, and oxygen (Ar/N2/O2) with a microwave resonator. Several spectral lines in the wavelength range of 200-450 nm were produced, guided by an Ar-N2-O2 plasma-filled fiber, and controlled by simply varying the gas ratio of this gas mixture. An optimum gas mixture ratio was experimentally and theoretically identified for the strongest emission in the DUV range of 200-275 nm. The developed DUV emitting plasma-core fiber represents an important milestone towards the development of tunable and miniaturized DUV/UV laser sources.

Antistaphylococcal ß-Lactams versus Vancomycin for Treatment of Infective Endocarditis Due to Methicillin-Susceptible Coagulase-Negative Staphylococci: a Prospective Cohort Study from the International Collaboration on Endocarditis.

The phenotypic expression of methicillin resistance among coagulase-negative staphylococci (CoNS) is heterogeneous regardless of the presence of the mecA gene. The potential discordance between phenotypic and genotypic results has led to the use of vancomycin for the treatment of CoNS infective endocarditis (IE) regardless of methicillin MIC values. In this study, we assessed the outcome of methicillin-susceptible CoNS IE among patients treated with antistaphylococcal ß-lactams (ASB) versus vancomycin (VAN) in a multicenter cohort study based on data from the International Collaboration on Endocarditis (ICE) Prospective Cohort Study (PCS) and the ICE-Plus databases. The ICE-PCS database contains prospective data on 5,568 patients with IE collected between 2000 and 2006, while the ICE-Plus database contains prospective data on 2,019 patients with IE collected between 2008 and 2012. The primary endpoint was in-hospital mortality. Secondary endpoints were 6-month mortality and survival time. Of the 7,587 patients in the two databases, there were 280 patients with methicillin-susceptible CoNS IE. Detailed treatment and outcome data were available for 180 patients. Eighty-eight patients received ASB, while 36 were treated with VAN. In-hospital mortality (19.3% versus 11.1%; P = 0.27), 6-month mortality (31.6% versus 25.9%; P = 0.58), and survival time after discharge (P = 0.26) did not significantly differ between the two cohorts. Cox regression analysis did not show any significant association between ASB use and the survival time (hazard ratio, 1.7; P = 0.22); this result was not affected by adjustment for confounders. This study provides no evidence for a difference in outcome with the use of VAN versus ASB for methicillin-susceptible CoNS IE.

Maternal perinatal undernutrition modifies lactose and serotranferrin in milk: relevance to the programming of metabolic diseases?

A close link between intrauterine growth restriction and development of chronic adult diseases such as obesity, diabetes, and hypertension has been established both in humans and animals. Modification of growth velocity during the early postnatal period (i.e., lactation) may also sensitize to the development of metabolic syndrome in adulthood. This suggests that milk composition may have long-lasting programming/deprogramming metabolic effects in the offspring. We therefore assess the effects of maternal perinatal denutrition on breast milk composition in a food-restricted 50% (FR50) rat model. Monosaccharides and fatty acids were characterized by gas chromatography, and proteins were profiled by surface-enhanced laser desorption/ionization-time-of-flight analysis in milk samples from FR50 and control rat dams. Milk analysis of FR50 rats demonstrated that maternal undernutrition decreases lactose concentration and modulates lipid profile at postnatal day 10 by increasing the unsaturated fatty acids/saturated fatty acids and diminishes serotransferrin levels at postnatal day 21. Our data indicate that maternal perinatal undernutrition modifies milk composition both quantitatively and qualitatively. These modifications by maternal nutrition open new perspectives to identify molecules that could be used in artificial milk to protect from the subsequent development of metabolic diseases.

Perinatal nutrition programs the hypothalamic melanocortin system in offspring.

Epidemiological studies initially suggested that maternal undernutrition leading to low birth weight may predispose for long-lasting energy balance disorders. High birth weight due to maternal obesity or diabetes, inappropriate early postnatal nutrition, and rapid catch-up growth, may also sensitize to increased risk of obesity. As stated by the Developmental Origin of Health and Disease concept, the perinatal perturbation of fetus/neonate nutrient supply might be a crucial determinant of individual programming of body weight set-point. The hypothalamic melanocortin system composed of the melanocortin receptor 4, its agonist α-melanin-stimulating hormone (α-MSH), and its antagonist agouti-related protein (AgRP) is considered as the main central anorexigenic pathway controlling energy homeostasis. Studies in numerous animal models demonstrated that this system is a prime target of developmental programming by maternal nutritional manipulation. In rodents, the perinatal period of life corresponds largely to the period of brain maturation (i. e., melanocortin neuronal differentiation and development of their neural projections). In contrast, these phenomena essentially take place before birth in bigger mammals. Despite these different developmental time windows, altricial and precocial species share several common offspring programming mechanisms. Offspring from malnourished dams present a hypothalamic melanocortin system with a series of alterations: impaired neurogenesis and neuronal functionality, disorganization of feeding pathways, modified glucose sensing, and leptin/insulin resistance. Overall, these alterations may account for the long-lasting dysregulation of energy balance and obesity. Following maternal malnutrition, hormonal and epigenetic mechanisms might be responsible for melanocortin system programming in offspring.

Antibiotic prophylaxis of infective endocarditis in patients with predisposing cardiac conditions: French cardiologists' implementation of current guidelines.

BACKGROUND: To prevent infective endocarditis (IE), with the exception of the United Kingdom, antibiotic prophylaxis (AP) is recommended in patients with predisposing cardiac conditions (PCCs) worldwide. To conclude on the relevance of this strategy, how the current guidelines are applied is a crucial point to investigate. The first aim of this study was to assess cardiologists' implementation of the current guidelines. The secondary objective was to identify specific areas where the training and knowledge of French cardiologists could be improved. METHODS: A national online survey was carried out among the 2228 cardiologist members of the French Society of Cardiology. RESULTS: The high risk PCCs for which IE AP is recommended were correctly identified by the vast majority of the respondents so that IE AP is mostly prescribed correctly in such patients. But only 12% identified all the right indications for IE AP according to 13 predefined PCCs (3 at high-risk, 6 at moderate-risk and 4 at low-risk of IE) so that some IE AP misuses are recorded, overprescription in particular. Only 47% prescribed the proper amoxicillin schedule and only 15% prescribed the appropriate clindamycin schedule in cases with penicillin allergy. CONCLUSION: This study evidenced relevant areas where the training of cardiologists could be improved such as knowledge of the risk of IE for certain PCCs and some common invasive dental procedures. Cardiologists' knowledge should be improved before any conclusion can be drawn on the relevance of this AP strategy and its influence on IE incidence.

The European Prader-Willi Syndrome Clinical Research Database: an aid in the investigation of a rare genetically determined neurodevelopmental disorder.

BACKGROUND: Prader-Willi Syndrome (PWS) is a rare genetically determined neurodevelopmental disorder with a complex phenotype that changes with age. The rarity of the syndrome and the need to control for different variables such as genetic sub-type, age and gender limits clinical studies of sufficient size in any one country. A clinical research database has been established to structure data collection and to enable multinational investigations into the development of children and adults with PWS. METHODS: As part of a joint basic science and clinical study of PWS funded through Framework 6 of the European Union (EU), an expert multidisciplinary group was established that included clinicians involved in PWS research and clinical practice, expert database software developers, and representatives from two national PWS Associations. This group identified the key issues that required resolution and the data fields necessary for a comprehensive database to support PWS research. RESULTS: The database consists of six 'index' entry points and branching panels and sub-panels and over 1200 data 'fields'. It is Internet-based and designed to support multi-site clinical research in PWS. An algorithm ensures that participant data are anonymous. Access to data is controlled in a manner that is compatible with EU and national laws. The database determines the assessments to be used to collect data thereby enabling the combining of data from different groups under specifically agreed conditions. The data collected at any one time will be determined by individual research groups, who retain control of the data. Over time the database will accumulate data on participants with PWS that will support future research by avoiding the need for repeat data collection of fixed data and it will also enable longitudinal studies and treatment trials. CONCLUSION: The development of the database has proved to be complex with various administrative and ethical issues to be addressed. At an early stage, it was important to clarify the exact function of the database. It was agreed that it was primarily to support grant-funded research rather than clinical practice. The most complex issues that had to be addressed were concerned with data ownership and establishing the rules for data entry, retrieval and sharing that are compatible with data protection laws, and which are likely to be acceptable to participants and their families and to individual research groups.

Comprehensive geriatric assessment in older patients suffering from infective endocarditis. A prospective multicentric cohort study.

OBJECTIVES: The aim was to describe the impact of infective endocarditis (IE) on functional, cognitive and nutritional statuses, and to estimate the influence of these parameters on surgical management and mortality. METHOD: This was a prospective study over 13 months in 14 French hospitals, including patients ≥75 years of age with definite or possible IE. A comprehensive geriatric assessment (CGA) was performed during the first week of hospitalization, including a retrospective estimation of functional status 2 months before hospitalization, and 3 months after. RESULTS: A total of 120 patients were included (mean age 83.1 ± 5.0 (75-101) years). IE was associated with a dramatic impairment of functional status between 2 months prior hospitalization and the first geriatric evaluation (90.8% able to walk vs. 35.5% (p < 0.0001), ADL (Activities in Daily Living) 5.0 ± 1.7 vs. 3.1 ± 2.1 (p < 0.0001)). The 19 operated patients (15.8%) had less comorbidities (cumulative illness rating scale geriatric 10.8 ± 8.2 vs. 15.3 ± 7.1 (p 0.0176)), better functional (ADL 5.9 ± 0.4 vs. 4.9 ± 1.8 (p 0.0171) and nutritional (mini nutritional assessment 20.4 ± 5.0 vs. 17.3 ± 6.2 (p 0.0501)) statuses than non-operated patients. Among all infectious, cardiac and geriatric parameters, body mass index (HR 0.9, range 0.8-1, p 0.05) and ADL at the time of the first evaluation (HR 0.7, range 0.6-0.9, p 0.002) were the sole independent predictors of the 3-month (32.5%) and 1-year mortality (42.5%). Three months later, the 57 assessed patients only partially recovered their ADL (3.7 ± 1.9 vs. 5.3 ± 1.4 2 months prior hospitalization and 4.6 ± 1.9 at the first CGA; p < 0.0001). CONCLUSION: Functional and nutritional abilities are crucial components that can be accurately explored through a CGA when managing IE in oldest patients.

[Timing and indications for surgical intervention in infective endocarditis]. / Indications et moment de l'intervention chirurgicale dans l'endocardite infectieuse.

This paper reviews current knowledge on the indications for and timing of cardiac surgery in patients with infective endocarditis. The main indications for surgery are haemodynamic compromise, persisting infection, peripheral embolisation, large size of vegetations, large valvular and paravalvular damage and infections caused by certain microorganisms.

Characteristics and regional variations of group D streptococcal endocarditis in France.

The proportion of infective endocarditis (IE) caused by group D streptococci (GDS; formerly Streptococcus bovis) increased markedly in France, to account for 25% of all cases of IE by 1999. In an attempt to explain this phenomenon, a comparative analysis of GDS and oral streptococci (OS) causing IE was performed. This study was based on data collected from a large cross-sectional population-based survey that was conducted in 1999. In total, 559 cases of definite IE were recorded, of which 142 involved GDS and 79 involved OS. Patients with GDS IE were older (62.7 vs. 56.6 years, p 0.01) and had a history of valve disease less frequently than did patients with OS IE (33.8% vs. 67.1%, p <0.0001). At-risk procedures for IE were performed less frequently in patients with GDS than in patients with OS (14.8% vs. 24.1%, p 0.08), but co-morbidities were more frequent in the GDS group (59.9% vs. 32.9%, p 0.0001). Diabetes, colon diseases and cirrhosis were also more frequent in the GDS group (p 0.006, p <0.0001 and p 0.08, respectively). Rural residents accounted for 31.0% of the GDS group, but for only 15.2% of the OS group (p 0.001). Likewise, the proportion of GDS IE was higher in regions with mixed (urban and rural) populations (Franche-Comté 81.8%, Marne 68.7%, Lorraine 70.3% and Rhône-Alpes 65.3%) than in exclusively urban regions (Paris and Ile de France 58.0%). Further investigations are required to elucidate the link in France between the incidence of GDS IE, rural residency and nutritional factors.

A pre-neoplastic epigenetic field defect in HCV-infected liver at transcription factor binding sites and polycomb targets.

The predisposition of patients with Hepatitis C virus (HCV) infection to hepatocellular carcinoma (HCC) involves components of viral infection, inflammation and time. The development of multifocal, genetically distinct tumours is suggestive of a field defect affecting the entire liver. The molecular susceptibility mediating such a field defect is not understood. One potential mediator of long-term cellular reprogramming is heritable (epigenetic) regulation of transcription, exemplified by DNA methylation. We studied epigenetic and transcriptional changes in HCV-infected livers in comparison with control, uninfected livers and HCC, allowing us to identify pre-neoplastic epigenetic and transcriptional events. We find the HCV-infected liver to have a pattern of acquisition of DNA methylation targeted to candidate enhancers active in liver cells, enriched for the binding sites of the FOXA1, FOXA2 and HNF4A transcription factors. These enhancers can be subdivided into those proximal to genes implicated in liver cancer or to genes involved in stem cell development, the latter distinguished by increased CG dinucleotide density and polycomb-mediated repression, manifested by the additional acquisition of histone H3 lysine 27 trimethylation (H3K27me3). Transcriptional studies on our samples showed that the increased DNA methylation at enhancers was associated with decreased local gene expression, results validated in independent samples from The Cancer Genome Atlas. Pharmacological depletion of H3K27me3 using the EZH2 inhibitor GSK343 in HepG2 cells suppressed cell growth and also revealed that local acquired DNA methylation was not dependent upon the presence of polycomb-mediated repression. The results support a model of HCV infection influencing the binding of transcription factors to cognate sites in the genome, with consequent local acquisition of DNA methylation, and the added repressive influence of polycomb at a subset of CG-dense cis-regulatory sequences. These epigenetic events occur before neoplastic transformation, resulting in what may be a pharmacologically reversible epigenetic field defect in HCV-infected liver.

Estimated risk of endocarditis in adults with predisposing cardiac conditions undergoing dental procedures with or without antibiotic prophylaxis.

BACKGROUND: Although antibiotic prophylaxis for infective endocarditis (IE) has been recommended for persons with predisposing cardiac conditions (PCCs) for many years, its efficacy, which has not been demonstrated, has been recently challenged. To assess its usefulness, we estimated the risk of developing IE after undergoing a dental procedure for which subjects would be eligible for prophylaxis, both in subjects having (protected procedure) or not having (unprotected procedure) received antibiotic prophylaxis. METHODS: The number of French persons with PCCs, the annual number of dental procedures in which subjects would be eligible for antibiotic prophylaxis, and the number of procedures that were unprotected were estimated on the basis of a survey performed on a sample of 2805 subjects aged 25-84 years. The annual number of IE cases possibly due to an unprotected procedure was estimated on the basis of a 1-year epidemiological study of IE conducted in an area inhabited by 16 million people. RESULTS: After standardization, extrapolation of results to the age-equivalent general population (39 millions subjects) indicated the following: first, 3.3% (95% confidence interval [CI], 2.6%-4%) of the subjects had PCC, 2.7 million (95% CI, 2.3-3.2 million) of whom had undergone at least 1 at-risk dental procedures within the survey year, and the procedures were unprotected in 62% of cases; second, 37 (95% CI, 18-68; 2.7%) of the 1370 annual IE cases in France were possibly related to unprotected procedures. Thus, the risks of developing IE were estimated to be 1 in 46,000 for unprotected procedures (1 in 10,700 and 1 in 54,300 for subjects with prosthetic and native valve PCC, respectively) and 1 in 150,000 for protected procedures. CONCLUSIONS: A huge number of prophylaxis doses would be necessary to prevent a very low number of IE cases.

[Reduction of rehospitalisation on elderly heart failure patients: A retrospective cohort VISage network]. / Réduction des réhospitalisations pour décompensation cardiaque chez la personne âgée : l'expérience du réseau VISage ­ filière insuffisance cardiaque.

BACKGROUND: Heart failure was a public health problem for one million of French patients. Patients are particularly concerned in rehospitalisation for this chronic pathology. A specific healthcare network was created to take care of patients with heart failure directly at home. This healthcare network (named VISage) brings a specific and adapted monitoring in heart failure. The main of this study was to evaluate the impact of healthcare network in rehospitalisation rate for heart failure of patients. MATERIAL AND METHODS: We conducted a retrospective cohort study with patients' hospital files of the CH Vienne. Patients who were included in our healthcare network (VISage) were screened. Primary endpoint was 30days, 6 months, and 1year rehospitalisation rate for heart failure before and after using healthcare network. RESULTS: One hundred and four patients with comorbidities were included between February 2009 and November 2015. A significant reduction of rehospitalisation rate for heart failure was observed before and after network: 0.65 (±0.52) vs. 0.17 (±0.43) 30days, 1.17 (±0.74) vs. 0.42 (±0.71) at 6 months and 1.35 (±0.95) vs. 0.47 (±0.74) at 1 year (P<0.0001). Results were significant for global rehospitalisation rate too. No significant differences were shown on hospital length of stay. CONCLUSION: Coordinated healthcare by a specific network at home for elderly is benefic for the rehospitalisation rate.

A critical appraisal of the quality of the management of infective endocarditis.

OBJECTIVES: The purpose of this study was to assess the quality of the management of infective endocarditis. BACKGROUND: Although many guidelines on the management of infective endocarditis exist, the quality of this management has not been evaluated. METHODS: We collected data on all patients (116) hospitalized with infective endocarditis over 1 year in all hospitals in the Rhône-Alpes region (France). RESULTS: Prophylactic antibiotics were not given before infective endocarditis to 8/11 cardiac patients at risk and who underwent an at risk procedure. Among the 55 cardiac patients at risk and with fever and who consulted a physician, blood cultures were not performed before antibiotic therapy was initiated for 32 patients. In-hospital antibiotic therapy was incorrect for 23 patients. The portal of entry was not treated for 16/61 patients with an accessible portal of entry. Among the 19 patients who had severe heart failure or fever persisting more than 2 weeks in spite of antibiotic therapy and who could have undergone early surgery, surgery was delayed for five, and not performed for three. Overall, the average score was 15/20. CONCLUSIONS: More information on the management of infective endocarditis should be widely disseminated to the physicians' and the dentists' communities and to the patients at risk.

Interaction and dissociation by ligands of estrogen receptor and Hsp90: the antiestrogen RU 58668 induces a protein synthesis-dependent clustering of the receptor in the cytoplasm.

The in vivo interaction of estrogen receptor (ER) and Hsp90, demonstrated in the absence of hormone by a nuclear cotranslocation assay of the cytoplasmic Hsp90 with the karyophilic receptor, was disrupted by agonist and antagonist ligands, which, after dissociating the Hsp90, allowed the chaperone protein to be relocalized in the cytoplasm. The pure antiestrogen RU 58668 (RU), which was unable to stimulate an estrogen-dependent reporter gene and completely inhibited its estradiol-induced activity, also profoundly modified the subcellular distribution of ER in a specific time- and dose-dependent manner; ER appeared as speckled fluorescent clusters mainly located in the perinuclear region of the cytoplasm. The kinetics of appearance and reversal of the RU-dependent ER mislocalization in the presence or absence of cycloheximide demonstrated 1) that this effect was reversed by RU withdrawal or estradiol (E2) treatment, and 2) that cycloheximide with RU inhibited and reversed the ER cytoplasmic mislocalization induced by RU alone. These results point to a protein synthesis-dependent step in the mechanism of action of this antiestrogen. After RU treatment, a large portion of ER was found in the particulate fraction of the cytoplasm. However, confocal and electron microscopic analysis showed that ER clusters were not associated with specific cytoplasmic organelles or compartments. Using ER mutants, it was found that the ligand binding domain was sufficient for RU to produce receptor mislocalization, while the constitutive nuclear localization signals were dispensable. We propose that the antiestrogenic properties of RU are primarily due to the induction of an aggregation-prone receptor conformation that cannot undertake the constitutive and the ligand-induced nuclear localization function of the receptor because it is sequestered in the cytoplasm by fast turning over protein(s). We predict that antiestrogens able to block ER nuclear localization will behave as pure antihormones and will inhibit all the nuclear action of ER elicited by agonistic ligands or by ligand-independent mechanisms such as growth factor stimulation.

[End-stage heart failure: quantity or quality of life?]. / Insuffisance cardiaque terminale: quantité ou qualité de vie ?

Several clinical trials testing the safety and efficacy of different positive inotropic agents in patients suffering form end-stage heart failure have confirmed that these drugs increase mortality. We nevertheless, use these agents regularly because of the presumption that they improve quality of life. However, this presumption, sound a priori, is not firmly anchored. When we prescribe these drugs, do we inform our patients? Do the patients ultimately decide whether to be treated with inotropic agents? What is the role of palliative care in the end-stage heart failure patient? We review the literature and reflect on these issues, long completely ignored, though beginning to elicit specific articles.

[Propionibacterium acnes infective endocarditis. Study of 11 cases and review of literature]. / Endocardites infectieuses a Propionibacterium acnes. Etude de 11 cas et revue de la littérature.

BACKGROUND: Propionibacterium acnes, a gram positive, anaerobic, skin commensal bacillus, is too often considered a biologic fluid contaminant, of blood cultures in particular. Its implication has been shown in various infections, including brain abscess, ocular infections, osteitis, and acne. It is also the cause of infective endocarditis (IE). METHODS: Retrospective, observational study of 11 patients with P. acnes IE, hospitalised between 1993 and 2001 at the Louis Pradel Hospital, Lyon-Bron, and review of 20 published cases. RESULTS: P. acnes IE is rare, though its prevalence is probably underestimated. It is most likely to affect men (71%), and affects all ages (children 4/31 cases). An entry point, probably cutaneous, is rarely confirmed. P. acnes IE often develops on valve prosthesis (42%), and embolisms are common (61%). The infective site is usually aortic (55%). The often-subtle symptoms and slow growth of the organism in vitro complicate the diagnosis, which is often made at a late stage, when valvular and peri-valvular destruction has become major. Despite the high sensitivity of P. acnes to most antimicrobials, a surgical intervention is very often needed (81%). The mortality is relatively high (15% to 27%). Examination of pathologic specimens by polymerase chain reaction increases the sensitivity and speed of its detection. The identification of P. acnes in a biologic specimen, valvular tissue in particular, requires a thorough knowledge of the clinical context before concluding to contamination, and mandates close surveillance of the patient. P. acnes can be the cause of IE long before it has been detected.

[Pathophysiology and therapeutic implications of left heart failure]. / Données physiopathologiques et implications thérapeutiques au cours de l'insuffisance cardiaque gauche.

PURPOSE: Heart failure is the ultimate step of most cardiovascular diseases. Its frequency increases regularly because of the progressive increase of life expectancy and better management of cardiovascular diseases. The prognosis is very poor (5-year mortality: 50%) as is quality of life; heart failure is a very costly disease. CURRENT KNOWLEDGE AND KEYS POINTS: Aims of treatment are improvement of symptoms and thus improvement of quality of life and increase of survival. The treatment systematically combines: general advice, dietary measures; medical treatment (with betablockers, ACE inhibitors and/or angiotensin II receptor antagonists, diuretics, in some cases aspirin or oral anticoagulants, digitalis and amiodarone) according to severity of heart failure, presence of congestion, aetiology, age; etiologic treatment if possible; treatment and prevention of precipitating and exacerbating factors. According to clinical and paraclinical features, one may propose cardiac multisite stimulation, cardiac surgery, physical stress training and cardiac transplantation. In order to decrease frequency of heart failure, prevention of cardiovascular diseases which lead to heart failure must be done as often is possible (hypertension, valvular heart disease, ischemic heart disease). FUTURE PROSPECTS AND PROJECTS: The future of the treatment of heart failure is the multidisciplinary management of heart failure (networks) led by hospital units specialized in heart failure.

[Whipple's disease endocarditis: report of 5 cases and review of the literature]. / Endocardites de la maladie de Whipple: cinq observations et revue de la littérature.

PURPOSE: Endocarditic lesions (infectious endocarditis) associated with Whipple's disease are exceptional. We report five cases from the cardiovascular and pneumologic hospital Louis Pradel in Lyon. METHOD: We have collected all cases of Tropheryma whipplei endocarditis diagnosed between 1995 and 2004. RESULTS: Five men with a mean age of 53 years at time of diagnosis. The symptoms were essentially cardiovascular: murmur, embolism in 3 cases, and heart failure secondary to valvular insufficiency in 2 cases. The valvular involvement, double in 3 cases, was more often aortic. Vegetations were present in all patients and valvular destruction sometimes very important. A low grade fever was present in 4 cases, associated with weight loss in 2 cases. The only extra-cardiac symptoms were arthralgias or arthritis in all cases, considered in 3 patients as seronegative rheumatoid arthritis, B27+ spondylarthritis, and psoriasic arthritis. Their was no other clinical manifestations of Whipple's disease, particularly digestive, ocular, neurologic or adenopathy, and duodenal biopsies secondarily performed in 4 cases were non contributive. This differs from literature as an extra-cardiac location was identified in 11 out of 17 cases. The diagnosis was obtained by histology and PCR on the cardiac valves, as all the patients underwent surgery. The evolution was favourable with a prolonged antibiotic therapy. CONCLUSIONS: These report confirms the existence of endocarditic forms of the Whipple's disease, in which the single extra-cardiac manifestation is rheumatologic, and reminds us the usefulness of histology and PCR on the cardiac valves at the time of valvular surgery.

One-year outcome following biological or mechanical valve replacement for infective endocarditis.

BACKGROUND: Nearly half of patients require cardiac surgery during the acute phase of infective endocarditis (IE). We describe the characteristics of patients according to the type of valve replacement (mechanical or biological), and examine whether the type of prosthesis was associated with in-hospital and 1-year mortality. METHODS AND RESULTS: Among 5591 patients included in the International Collaboration on Endocarditis Prospective Cohort Study, 1467 patients with definite IE were operated on during the active phase and had a biological (37%) or mechanical (63%) valve replacement. Patients who received bioprostheses were older (62 vs 54years), more often had a history of cancer (9% vs 6%), and had moderate or severe renal disease (9% vs 4%); proportion of health care-associated IE was higher (26% vs 17%); intracardiac abscesses were more frequent (30% vs 23%). In-hospital and 1-year death rates were higher in the bioprosthesis group, 20.5% vs 14.0% (p=0.0009) and 25.3% vs 16.6% (p<.0001), respectively. In multivariable analysis, mechanical prostheses were less commonly implanted in older patients (odds ratio: 0.64 for every 10years), and in patients with a history of cancer (0.72), but were more commonly implanted in mitral position (1.60). Bioprosthesis was independently associated with 1-year mortality (hazard ratio: 1.298). CONCLUSIONS: Patients with IE who receive a biological valve replacement have significant differences in clinical characteristics compared to patients who receive a mechanical prosthesis. Biological valve replacement is independently associated with a higher in-hospital and 1-year mortality, a result which is possibly related to patient characteristics rather than valve dysfunction.

Human skin as target for aldosterone: coexpression of mineralocorticoid receptors and 11 beta-hydroxysteroid dehydrogenase.

The expression of mineralocorticoid receptors (MR) and 11 beta-hydroxysteroid dehydrogenase (11HSD) activity has been investigated in the epidermis and appendages of the human skin. Aldosterone binds to MR and regulates sodium transport in tight epithelia. Mineralocorticoid selectivity is achieved through coexpression of MR and 11HSD, which prevents permanent MR occupancy by glucocorticoids. Some forms of hypertension may involve abnormalities of MR and/or 11HSD. However, their direct assessment in humans remains difficult in the kidney or colon. This led us to explore this system in human skin easily accessible to biopsy. In situ hybridization with specific MR complementary ribonucleic acid probes and immunohistochemistry using three different anti-MR antibodies showed that MR was expressed at both the messenger ribonucleic acid and protein levels in the keratinocytes of the epidermis, in the sweat and sebaceous glands, and in the hair follicles. A significant 11HSD activity was found in isolated sweat gland ducts (5 fmol/3-mm length.10-min incubation with 10 nmol/L corticosterone as substrate) and was very low in the epidermis. In both structures, reductase activity was 10 times lower than that of dehydrogenase. Studies on the cofactor specificity of the enzyme showed a nicotinamide-adenine-dinucleotide preference in sweat glands, contrasting with a nicotinamide-adenine-dinucleotide phosphate dependence in epidermis. Human skin appears as a new target for aldosterone because it coexpresses MR and 11HSD. Our findings present the possibility to explore the functionality of the MR system in human tissue and its implications in various physiopathological situations.