Hôpital Saint-Jacques

The ESC Guidelines represent the views of the ESC and were arrived at after careful consideration of the available evidence at the time they were written. Health professionals are encouraged to take them fully into account when exercising their clinical judgement. The guidelines do not, however, override the individual responsibility of health professionals to make appropriate decisions in the circumstances of the individual patients, in consultation with that patient, and where appropriate and necessary the patient's guardian or carer. It is also the health professional's responsibility to verify the rules and regulations applicable to drugs and devices at the time of prescription.

OBJECTIVE: Different sets of diagnostic criteria have been proposed for Sjögren's syndrome (SS), but none have been validated with a large series of patients or in a multicenter study. We conducted the present study involving 26 centers from 12 countries (11 in Europe, plus Israel), with the goals of reaching a consensus on the diagnostic procedures for SS and defining classification criteria to be used in epidemiologic surveys and adopted by the scientific community. METHODS: The study protocol was subdivided into two parts. For part I, questionnaires regarding both ocular and oral involvement were developed; they included 13 questions and 7 questions, respectively. For part II a limited set of diagnostic tests was selected, and the exact procedure to be followed in performing these tests was defined. Part I of the study included 240 patients with primary SS and 240 age- and sex-matched controls. Two hundred forty-six patients with primary SS, 201 with secondary SS, 113 with connective tissue diseases but without associated SS, and 133 control patients were studied in part II. RESULTS: The study resulted in (a) the validation of a simple 6-item questionnaire for determination of dry eyes and dry mouth, which showed good discriminant power between patients and controls, to be used in the initial screening for sicca syndrome; and (b) the definition of a new set of criteria for the classification of SS. The sensitivity and specificity of the criteria in correctly identifying patients with either the primary or the secondary variant of SS were also determined. CONCLUSION: Using the findings of this prospective multicenter European study, general agreement can be reached on the diagnostic procedures to be used for patients with SS. Final validation of the preliminary classification criteria for SS is underway.

BACKGROUND: Observational studies showed that the profile of infective endocarditis (IE) significantly changed over the past decades. However, most studies involved referral centers. We conducted a population-based study to control for this referral bias. The objective was to update the description of characteristics of IE in France and to compare the profile of community-acquired versus healthcare-associated IE. METHODS: A prospective population-based observational study conducted in all medical facilities from 7 French regions (32% of French individuals aged ≥18 years) identified 497 adults with Duke-Li-definite IE who were first admitted to the hospital in 2008. Main measures included age-standardized and sex-standardized incidence of IE and multivariate Cox regression analysis for risk factors of in-hospital death. RESULTS: The age-standardized and sex-standardized annual incidence of IE was 33.8 (95% confidence interval [CI], 30.8-36.9) cases per million inhabitants. The incidence was highest in men aged 75-79 years. A majority of patients had no previously known heart disease. Staphylococci were the most common causal agents, accounting for 36.2% of cases (Staphylococcus aureus, 26.6%; coagulase-negative staphylococci, 9.7%). Healthcare-associated IE represented 26.7% of all cases and exhibited a clinical pattern significantly different from that of community-acquired IE. S. aureus as the causal agent of IE was the most important factor associated with in-hospital death in community-acquired IE (hazard ratio [HR], 2.82 [95% CI, 1.72-4.61]) and the single factor in healthcare-associated IE (HR, 2.54 [95% CI, 1.33-4.85]). CONCLUSIONS: S. aureus became both the leading cause and the most important prognostic factor of IE, and healthcare-associated IE appeared as a major subgroup of the disease.

Allogeneic hematopoietic stem-cell transplantation (HSCT) is the only curative treatment for sickle cell disease (SCD); nevertheless, its use has been limited by the risk of transplantation-related mortality (TRM). Between November 1988 and December 2004, 87 consecutive patients with severe SCD ranging from 2 to 22 years of age received transplants in France. Cerebral vasculopathy was the principal indication for transplantation (55 patients). All the patients received grafts from a sibling donor after a myeloablative conditioning regimen (CR). The only change in the CR during the study period was the introduction of antithymocyte globulin (ATG) in March 1992. The rejection rate was 22.6% before the use of ATG but 3% thereafter. With a median follow-up of 6 years (range, 2.0 to 17.9 years), the overall and event-free survival (EFS) rates were 93.1% and 86.1%, respectively. Graft versus host disease (GVHD) was the main cause of TRM. Importantly, cord blood transplant recipients did not develop GVHD. No new ischemic lesions were detected after engraftment, and cerebral velocities were significantly reduced. The outcome improved significantly with time: the EFS rate among the 44 patients receiving transplants after January 2000 was 95.3%. These results indicate that HLA-identical sibling HSCT after myeloablative conditioning with ATG should be considered as a standard of care for SCD children who are at high risk for stroke.

BACKGROUND: The optimal duration of oral anticoagulant therapy after a first episode of venous thromboembolism remains controversial. METHODS AND RESULTS: We performed an open-label, randomized trial comparing a short oral anticoagulant course (3 months for proximal deep vein thrombosis [P-DVT] and/or pulmonary embolism [PE]; 6 weeks for isolated calf DVT [C-DVT]) with a long course of therapy (6 months for P-DVT/PE; 12 weeks for C-DVT). The outcome events were recurrences and major, minor, or fatal bleeding complications. A total of 736 patients were enrolled. There were 23 recurrences of venous thromboembolism in the short treatment group (6.4%) and 26 in the long treatment group (7.4%); the 2 treatment regimens had an equivalent effect. For the hemorrhage end point, the difference between the short and the long treatment groups was not significant: 15.5% versus 18.4% for all events (P=0.302), 1.7% versus 2.8% (P=0.291) for major events, and 13.9% versus 15.3% for minor bleeding. Subgroup analysis demonstrated that the rate of recurrence was lower for C-DVT than for P-DVT or PE. CONCLUSIONS: After isolated C-DVT, 6 weeks of oral anticoagulation is sufficient. For P-DVT or PE, we demonstrated an equivalence between 3 and 6 months of anticoagulant therapy. For patients with temporary risk factors who have a low risk of recurrence, 3 months of treatment seems to be sufficient. For patients with idiopathic venous thromboembolism or permanent risk factors who have a high risk of recurrence, other trials are necessary to assess prolonged therapy beyond 6 months.

BACKGROUND: Drug patch tests (PTs) can reproduce delayed hypersensitivity to drugs and entail a moderate re-exposure of patients to offending drugs. OBJECTIVES: To determine the value of PTs for identifying the responsible drug in severe cutaneous adverse drug reactions (SCARs) such as acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS) and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). METHODS: In a multicentre study, PTs were conducted on patients referred for DRESS, AGEP or SJS/TEN within 1 year of their SCAR. All drugs administered in the 2 months prior to and the week following the onset of the SCAR were tested. RESULTS: Among the 134 patients included (48 male, 86 female; mean age 51·7 years), positive drug PTs were obtained for 24 different drugs. These included positive tests for 64% (46/72) of patients with DRESS, 58% (26/45) of those with AGEP and 24% (4/17) of those with SJS/TEN, with only one relapse of AGEP. The value of PTs depended on the type of drug and the type of SCAR (e.g. carbamazepine was positive in 11/13 DRESS cases but none of the five SJS/TEN cases). PTs were frequently positive for beta lactams (22 cases), pristinamycin (11 cases) and in DRESS with pump proton inhibitors (five cases), but were usually negative for allopurinol and salazopyrin. Of 18 patients with DRESS, eight had virus reactivation and positive PTs. In DRESS, multiple drug reactivity was frequent (18% of cases), with patients remaining sensitized many years later. CONCLUSIONS: PTs are useful and safe for identifying agents inducing SCAR.

Abstract Anthropogenic global warming at a given time is largely determined by the cumulative total emissions (or stock) of long-lived climate pollutants (LLCPs), predominantly carbon dioxide (CO 2 ), and the emission rates (or flow) of short-lived climate pollutants (SLCPs) immediately prior to that time. Under the United Nations Framework Convention on Climate Change (UNFCCC), reporting of greenhouse gas emissions has been standardised in terms of CO 2 -equivalent (CO 2 -e) emissions using Global Warming Potentials (GWP) over 100-years, but the conventional usage of GWP does not adequately capture the different behaviours of LLCPs and SLCPs, or their impact on global mean surface temperature. An alternative usage of GWP, denoted GWP*, overcomes this problem by equating an increase in the emission rate of an SLCP with a one-off “pulse” emission of CO 2 . We show that this approach, while an improvement on the conventional usage, slightly underestimates the impact of recent increases in SLCP emissions on current rates of warming because the climate does not respond instantaneously to radiative forcing. We resolve this with a modification of the GWP* definition, which incorporates a term for each of the short-timescale and long-timescale climate responses to changes in radiative forcing. The amended version allows “CO 2 -warming-equivalent” (CO 2 -we) emissions to be calculated directly from reported emissions. Thus SLCPs can be incorporated directly into carbon budgets consistent with long-term temperature goals, because every unit of CO 2 -we emitted generates approximately the same amount of warming, whether it is emitted as a SLCP or a LLCP. This is not the case for conventionally derived CO 2 -e.

Our previous studies reported the performance of Macroporous Biphasic Calcium Phosphate (MBCP) in spine fusion. In the present study, this material was used in block forms in selected patients with tumoral resection in long bone. Two cases were chosen with large benign bone tumors. Clinical and radiographic assessments, CT scans, and NMR were performed after 16 months, and in one case control biopsies were taken. In order to understand the kinetic process of biodegradation of the MBCP blocks and bone formation at the expense of the ceramics, an experimental study in surgically created bond defects in canine femoral cortices was made. The MBCP blocks recovered after implantation period from 2 to 18 weeks were analyzed using histological, stereological, ultrastructural, electron microprobe, and IR spectroscopy analyses. This study demonstrated the efficiency of MBCP blocks for filling pathological defects in human long bone. The biointegration process of the MBCP blocks was due to a partial dissolution of the ceramics crystals (b-TCP content) by multinucleated cells. Simultaneously, bone ingrowth at the expense of the ceramic is observed. The new bone formation inside the MBCP macropores and in the spaces between the blocks, involved the formation of a new cortical bone on the outer part, and a trabecularlike bone with bone marrow in the inner part of the implant. The biological resorption of the MBCP ceramic decreased after 1 month implantation in dog, due to the protective role of the newly formed lamellar bone on the surface and in the core of the ceramics.

Factor VIII or factor IX replacement is frequently impossible in inhibitor-developing hemophiliacs, because of the level of the inhibitor titer. Activated prothrombin complex concentrates are one of the available options to treat the bleeding episodes in such patients. However, the efficacy of these products and the associated thrombogenic risk, particularly in prolonged administration such as employed during surgeries, are important concerns for hemophilia care providers. We performed a multicenter retrospective study to evaluate the use of FEIBA (Factor Eight Bypassing Activity) in France, and data is presented on 433 bleeding episodes, including surgical procedures, concerning 60 patients from 15 hemophilia centers. The efficacy was judged as good or excellent in 352 episodes (81.3%), poor in 73 episodes (16.9%) and non-existent in 8 episodes (1.8%). Minor and major surgical procedures were successfully performed using FEIBA as a second-line therapy after human or porcine factor VIII, and in some occasions FEIBA was utilized as the only substitution product. The tolerance was assessed as good in 428 episodes (98.8%), but in 5 cases adverse effects were reported. Only 3 patients out of 52 regularly evaluated (5.8%) were HIV-seropositive, and for two of them the seroconversion occurred prior to the first use of FEIBA. In contrast, 80.4% of the patients were HCV-seropositive. An anamnestic response after the administration of FEIBA was noted in 31.5% of cases. This study points out the main features of the use of FEIBA in France, and particularly the low HIV seroprevalence in the patients treated. The good efficacy and the excellent tolerance still confer to this product a place to consider in the therapeutic options for the treatment of inhibitor-developing hemophiliacs or in acquired hemophilia.

BACKGROUND: recent short-term observations have shown an improvement in cardiac function and heart failure symptoms from atrio-biventricular pacing. This study was designed to assess the safety and feasibility of an atrio-biventricular transvenous pacing system, and examine the long-term effects of cardiac resynchronization in patients with advanced heart failure and ventricular conduction abnormalities. METHODS AND RESULTS: between August, 1997 and November, 1998, 103 patients received a cardiac resynchronization system (CRS) consisting of a pulse generator interfaced with an atrio-biventricular lead system, including a lead designed for left ventricular (LV) pacing via cardiac veins. Baseline evaluation included 12-lead electrocardiogram, estimation of New York Heart Association (NYHA) functional class, assessment of quality of life (QOL), and distance covered during a 6-min walk (6-MW). Detailed echocardiographic data were also collected in a subset of 46 patients. Measurements were repeated in all surviving patients at 1, 3, 6 and 12 months after implantation of the CRS. A single, self-limiting procedure-related complication occurred. Over a follow-up of 12 months, 21 patients died. The 12-month actuarial survival was 78% (CI 70-87%). Nine surviving patients were withdrawn from the study during long-term follow-up for miscellaneous reasons. At each point of follow-up, a significant shortening of QRS duration was measured. In addition, significant improvements were observed in mean NYHA functional class, 6-MW and QOL score. In the 46 patients with complete echocardiographic data, LV ejection fraction increased from 21.7+/-6.4% at baseline to 26.1+/-9.0% at last follow-up (P = 0.006), LV end diastolic dimension decreased from 72.7+/-9.2 to 71.6+/-9.1 mm (P = 0.233), interventricular mechanical delay decreased from 27.5+/-32.1 to 20.3+/-25.5 ms (P = 0.243), mitral regurgitation apical four-chamber area decreased from 7.66+/-5.5 to 6.69+/-5.9 cm(2) (P = 0.197), and left ventricular filling time increased from 363+/-127 to 408+/-111 ms (P = 0.002). CONCLUSIONS: long-term cardiac resynchronization can be safely and reliably achieved by transvenous atrial synchronized right and left ventricular pacing. These changes were accompanied by clinically relevant improvements in functional status and QOL, as well as a measurable increase in LV performance. The outcome of randomised controlled trials is awaited.

Vitamin C is known for its antioxidant potential and activity in the collagen biosynthetic pathway. Photoprotective properties of topically applied vitamin C have also been demonstrated, placing this molecule as a potential candidate for use in the prevention and treatment of skin ageing. A topically applied cream containing 5% vitamin C and its excipient were tested on healthy female volunteers presenting with photoaged skin on their low-neck and arms in view to evaluate efficacy and safety of such treatment. A double-blind, randomized trial was performed over a 6-month period, comparing the action of the vitamin C cream vs. excipient on photoaged skin. Clinical assessments included evaluation at the beginning and after 3 and 6 months of daily treatment. They were performed by the investigator and compared with the volunteer self assessment. Skin relief parameters were determined on silicone rubber replicas performed at the same time-points. Cutaneous biopsies were obtained at the end of the trial and investigated using immunohistochemistry and electron microscopy. Clinical examination by a dermatologist as well as self-assessment by the volunteers disclosed a significant improvement, in terms of the 'global score', on the vitamin C-treated side compared with the control. A highly significant increase in the density of skin microrelief and a decrease of the deep furrows were demonstrated. Ultrastructural evidence of the elastic tissue repair was also obtained and well corroborated the favorable results of the clinical and skin surface examinations. Topical application of 5% vitamin C cream was an effective and well-tolerated treatment. It led to a clinically apparent improvement of the photodamaged skin and induced modifications of skin relief and ultrastructure, suggesting a positive influence of topical vitamin C on parameters characteristic for sun-induced skin ageing.

The persistence of transcriptionally silent but replication-competent HIV-1 reservoirs in Highly Active Anti-Retroviral Therapy (HAART)-treated infected individuals, represents a major hurdle to virus eradication. Activation of HIV-1 gene expression in these cells together with an efficient HAART has been proposed as an adjuvant therapy aimed at decreasing the pool of latent viral reservoirs. Using the latently-infected U1 monocytic cell line and latently-infected J-Lat T-cell clones, we here demonstrated a strong synergistic activation of HIV-1 production by clinically used histone deacetylase inhibitors (HDACIs) combined with prostratin, a non-tumor-promoting nuclear factor (NF)- kappaB inducer. In J-Lat cells, we showed that this synergism was due, at least partially, to the synergistic recruitment of unresponsive cells into the expressing cell population. A combination of prostratin+HDACI synergistically activated the 5' Long Terminal Repeat (5'LTR) from HIV-1 Major group subtypes representing the most prevalent viral genetic forms, as shown by transient transfection reporter assays. Mechanistically, HDACIs increased prostratin-induced DNA-binding activity of nuclear NF-kappaB and degradation of cytoplasmic NF-kappaB inhibitor, IkappaBalpha . Moreover, the combined treatment prostratin+HDACI caused a more pronounced nucleosomal remodeling in the U1 viral promoter region than the treatments with the compounds alone. This more pronounced remodeling correlated with a synergistic reactivation of HIV-1 transcription following the combined treatment prostratin+HDACI, as demonstrated by measuring recruitment of RNA polymerase II to the 5'LTR and both initiated and elongated transcripts. The physiological relevance of the prostratin+HDACI synergism was shown in CD8(+)-depleted peripheral blood mononuclear cells from HAART-treated patients with undetectable viral load. Moreover, this combined treatment reactivated viral replication in resting CD4(+) T cells isolated from similar patients. Our results suggest that combinations of different kinds of proviral activators may have important implications for reducing the size of latent HIV-1 reservoirs in HAART-treated patients.

BACKGROUND AND PURPOSE: Hemorrhagic transformation (HT) is the most critical complication of thrombolytics in clinical trials in acute stroke. The aim of this study was to determine the rates and the predictors of HT in the Multicenter Acute Stroke Trial-Europe (MAST-E) study. METHODS: We performed a post hoc analysis of MAST-E data designed to assess the safety and efficacy of streptokinase administered intravenously within 6 hours of stroke onset. HT included all intracerebral hemorrhages and symptomatic hemorrhages (SHT) associated with clinical worsening. The predictors of HT and SHT were determined using multivariate modeling. RESULTS: Among the 310 patients included, 159 patients had HT and 37 SHT (97 and 33 in the streptokinase group and 62 and 4 in the placebo group, respectively). Patients with SHT had significantly more atrial fibrillation, diabetes mellitus, no heparin use, streptokinase treatment, and early CT signs. In the multivariate analysis, HT was predicted by early CT signs and streptokinase treatment. SHT was predicted by diabetes mellitus, early CT signs, streptokinase treatment, and the interaction between streptokinase treatment and decreased level of consciousness. Among the streptokinase-treated patients, the same predictors remained. CONCLUSIONS: The relative risks of HT after streptokinase were in the same range in MAST-E as in other streptokinase and tPA trials. Early CT signs were strong predictors of both HT and SHT, stressing that these patients are at high risk of bleeding. In our study, the predictors of HT and SHT were similar to those of tPA trials in acute stroke.

With a background of experimental studies on macroporous biphasic calcium phosphate (MBCP) in canine spine fusion, MBCP was investigated in 11- to 18-year-old patients with scoliosis treated by spinal fusion. Twelve cases were chosen for whom enough bone graft was difficult to obtain (severe neurologic scoliosis and osteogenesis imperfecta). MBCP blocks were used in combination with a specific strong fixation (Cotrel-Dubousset instrumentation). Clinical and roentgenogram assessments were performed up to 24 months. In two cases, biopsies were obtained. Histologic, ultrastructural, and microanalysis studies demonstrated the effectiveness of MBCP implants combined with a strong stabilization as bone graft substitutes for spine fusion. Clinical and biologic assessments were normal, and the histologic and ultrastructural evaluation demonstrated the bioactivity and the osteoconduction of this material. Partial resorbability of the MBCP blocks involved lamellar bone formation at the expense of the ceramic.

The aim of this study was to investigate constitutional and environmental determinants of non-melanocytic skin cancer among different populations from south Europe. Between 1989 and 1993 we interviewed incident cases and a random population sample of controls from five centres where a cancer registry was operating, whereas we selected a sample of hospital-based cases and controls from three other centres. Controls were stratified according to the age and sex distribution of cases. In all, 1549 cases of basal cell carcinoma (BCC), 228 of squamous cell carcinoma (SCC) and 1795 controls were interviewed. Both cancers affected primarily sun-exposed sites such as face, head and neck, but the prevalence of BCC on the trunk was higher than for SCC. Pigmentary traits such as hair and eye colour as well as tendency to sunburn were strong and independent indicators of risk for both BCC and SCC. In SCC, adjusted odds ratios (ORs) ranged from 1.6 for fair hair colour to 12.5 for red hair. Light-blonde hair entailed a risk of about 2 for BCC. Pale eye colour was associated with a risk of 1.8 for SCC and 1.4 for BCC. Subjects who always burn and never tan showed an adjusted OR of 2.7 for BCC and 2.0 for SCC. A history of sunburns and a young age at first sunburn were associated with an increased risk for BCC only (OR 1.7). Pigmentary traits and sun sensitivity of the skin confirmed their role as risk indicators. The effect of sunburns, as an indicator of both exposure and sun sensitivity of the skin, is less clear. Nevertheless, its association with BCC suggests, by analogy with melanoma, a relationship with intense sun exposure. Conversely, SCC would require prolonged exposure to sunlight.

AIM: The aim of this study was to assess the independent role of cerebral lesions on ultrasound scan, and several other neonatal and obstetric factors, as potential predictors of cerebral palsy (CP) in a large population-based cohort of very preterm infants. METHOD: As part of EPIPAGE, a population-based prospective cohort study, perinatal data and outcome at 5 years of age were recorded for 1812 infants born before 33 weeks of gestation in nine regions of France in 1997. RESULTS: The study group comprised 942 males (52%) and 870 females with a mean gestational age of 30 weeks (SD 2 wks; range 24-32 wks) and a mean birthweight of 1367 g (SD 393 g; range 450-2645 g). CP was diagnosed at 5 years of age in 159 infants (prevalence 9%; 95% confidence interval [CI] 7-10%), 97 males and 62 females, with a mean gestational age of 29 weeks (SD 2 wks; range 24-32 wks) and a mean birthweight of 1305 g (SD 386 g; range 500-2480 g). Among this group, 67% walked without aid, 14% walked with aid, and 19% were unable to walk. Spastic, ataxic, and dyskinetic CP accounted for 89%, 7%, and 4% of cases respectively. The prevalence of CP was 61% among infants with cystic periventricular leukomalacia, 50% in infants with intraparenchymal haemorrhage, 8% in infants with grade I intraventricular haemorrhage, and 4% in infants without a detectable cerebral lesion. After controlling for cerebral lesions and obstetric and neonatal factors, only male sex (odds ratio [OR] 1.52; 95% CI 1.03-2.25) and preterm premature rupture of membranes or preterm labour (OR 1.72; 95% CI 0.95-3.14) were predictors of the development of CP in very preterm infants. INTERPRETATION: Cerebral lesions were the most important predictor of CP in very preterm infants. In addition, infant sex and preterm premature rupture of membranes or preterm labour were also independent predictors of CP.

Renal transplant recipients have disproportionately high rates of arteriosclerotic outcomes, and recent studies provided controlled evidence that clinically stable renal transplant recipients have an excess prevalence of hyperhomocysteinemia. Few studies suggest that hyperhomocysteinemia may be a cardiovascular risk factor in renal transplant recipients. In the study presented here, the association between atherosclerotic events and homocysteine concentrations was examined in 207 stable renal transplant recipients. The role of hyperhomocysteinemia was analyzed with respect to other known cardiovascular risk factors. The mean follow-up was 21.2 +/- 1.9 mo (range, 14 to 26). Mean total homocysteine (tHcy) was 21.1 +/-9.5 micromol/L and median concentration was 19 micromol/L. Seventy percent of patients (n = 153) were hyperhomocysteinemic (values >15 micromol/L). tHcy correlated negatively with folate concentration (r = -0.3; P < 0.01). tHcy was closely related to creatinine concentration (r = 0.54; P < 0.001). Cardiovascular disease events (CVE) including death were observed in 30 patients (14.5 %; 7.34 events per 1000 person-months of follow-up). Fasting tHcy values were higher in patients who experienced CVE (31.5 +/- 10.3 versus 17.8 +/- 7.5; P < 0.001). Cox regression analysis showed that tHcy was a risk factor for cardiovascular complications (relative risk [RR] 1.06; 95% confidence interval (95% CI), 1.04 to 1.09; P < 0.0001). This corresponds to an increase in RR for CVE of 6% per micromol/L increase in tHcy concentration. Age (RR 1.55; 95% CI, 1.09 to 2.19; P < 0.01) and creatinine concentration (RR 1.34; 95% CI, 1.08 to 1.66; P < 0.01) were also independent predictors for CVE. This study demonstrates that elevated fasting tHcy is an independent risk factor for the development of CVE in chronic stable renal transplant recipients. Randomized, placebo-controlled homocysteine studies of the effect of tHcy lowering on CVE rates are urgently required in this patient population.

IL-23 is a pro-inflammatory cytokine belonging to the IL-12 cytokine family. IL-23 is essential for the differentiation of Th17 lymphocytes, a subtype of T lymphocyte implicated in chronic inflammatory/autoimmune mediated diseases. IL-23 and Th17 correspond to a new axis that drives immune activation and chronic inflammation through the differentiation and activation of Th17 cells. Animal models of chronic inflammatory diseases such as chronic joint diseases, inflammatory bowel diseases and demyelinating diseases strongly suggest the involvement of this cytokine pathway. Thus, IL-23/Th17 is considered as a relevant therapeutic target in autoimmune driven diseases, and biological agents blocking IL-23 or IL-17 are currently being developed. Ustekinumab is a monoclonal antibody targeting the common p40 subunit of IL-12 and IL-23. This treatment has demonstrated its efficacy over placebo in randomized placebo controlled trials and is currently licensed for the treatment of psoriasis. It has also demonstrated its efficacy in psoriatic arthritis. Results for Crohn's disease were less evident, while ustekinumab was ineffective in multiple sclerosis. Secukinumab is an IL-17A monoclonal antibody that is under development and preliminary results have suggested its efficacy in inflammatory mediated diseases such as psoriasis and ankylosing spondylitis. Several other IL-23 or IL-17 neutralizing agents are being evaluated in clinical trials. The biological properties of the IL-23/Th17/IL-17 axis and the clinical applications of the drugs that aim to block its functions are reviewed here. Targeting the IL-23/Th17 axis seems to be a relevant and realistic therapeutic approach and these new agents pave the way for additive and alternative treatments to currently available biologics in chronic inflammatory diseases.

BACKGROUND: External acuminata condylomata (EAC) are among the most common sexually transmitted diseases. Although it is understood that low-risk human papillomavirus (HPV) genotypes 6 and 11 are associated with EAC, there have only been a few, small, published studies reporting the genotype-specific prevalence of HPV. The objective of our study was to assess the prevalence of HPV genotypes for a large number of cases involving both men and women and to evaluate the potential benefit of a quadrivalent (genotypes 6, 11, 16, and 18) HPV vaccine in France. METHODS: A total of 256 women and 260 men who presented with EAC to French gynecologists, dermatologists, and proctologists were prospectively recruited during the period January through April 2007. Specimens were collected with a cytobrush, and the HPV genotype was determined using the INNO-LiPA assay (Innogenetics), which detects 24 HPV genotypes. RESULTS: Four hundred twenty-three beta-globin-positive samples could be analyzed. The median age of patients was 30 years (range, 18-72 years). The overall prevalence of HPV DNA in patients with EAC was 99% (33% of patients were coinfected with another pathogen). Low-risk genotypes predominated, with a prevalence of 89%. The most prevalent genotypes were 6 (69%) and 11 (16%), followed by 16 (9%), 51 (8%), 52 (7%), 66 (6%) 53 (5%), 31 (3%), and 18 (3%). The cumulative prevalence of genotypes 6 and 11 was 83%, and the cumulative prevalence of genotypes 6, 11, 16, and 18 was 88%. CONCLUSIONS: This study is, to our knowledge, the first large, multicenter survey to provide solid data on HPV genotype distribution among patients with EAC. Our results provide strong evidence that, in France, the most prevalent HPV genotypes in persons with EAC are 6 and 11. Because of its 99% efficacy for the prevention of EAC and a vaccine coverage of 100%, the quadrivalent HPV vaccine could prevent 62%-87% of EAC cases in France.

The permeability of bacterial outer membranes was assayed by coupling the influx of highly hydrophobic probes, 3-oxosteroids, with their subsequent oxidation catalysed by 3-oxosteroid delta 1-dehydrogenase, expressed from a gene cloned from Pseudomonas testosteroni. In Salmonella typhimurium producing wild-type lipopolysaccharide, the permeability coefficients for uncharged steroids were 0.45 to 1 x 10(-5) cm s-1, and the diffusion appeared to occur mainly through the lipid bilayer domains of the outer membrane. These rates are one or two magnitudes lower than that expected for their diffusion through the usual biological membranes. The permeation rates were markedly increased (up to 100 times) when the lipopolysaccharide leaflet was perturbed either by adding deacylpolymyxin or by introducing mutations leading to the production of deep rough lipopolysaccharides. An amphiphilic, negatively charged probe, testosterone hemisuccinate, penetrated much more slowly than the uncharged steroids. Study of various Gram-negative species revealed that P. testosteroni, Pseudomonas acidovorans, and Acinetobacter calcoaceticus showed higher outer membrane permeability to steroid probes and higher susceptibility to hydrophobic agents such as fusidic acid, novobiocin and crystal violet relative to S. typhimurium and Escherichia coli.