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Burrel S.,University Pierre and Marie Curie | Burrel S.,Pitie Salpetriere University Hospital | Ait-Arkoub Z.,Pitie Salpetriere University Hospital | Voujon D.,Pitie Salpetriere University Hospital | And 7 more authors.
Journal of Clinical Microbiology | Year: 2013

The complete 154-kbp linear double-stranded genomic DNA sequence of herpes simplex virus 2 (HSV-2), consisting of two extended regions of unique sequences bounded by a pair of inverted repeat elements, was published in 1998 and since then has been widely employed in a wide range of studies.Throughout the HSV-2 genome are scattered 150 microsatellites (also referred to as short tandem repeats) of 1-to 6-nucleotide motifs, mainly distributed in noncoding regions.Microsatellites are considered reliable markers for genetic mapping to differentiate herpesvirus strains, as shown for cytomegalovirus and HSV-1.The aim of this work was to characterize 12 polymorphic microsatellites within the HSV-2 genome by use of 3 multiplex PCR assays in combination with length polymorphism analysis for the rapid genetic differentiation of 56 HSV-2 clinical isolates and 2 HSV-2 laboratory strains (gHSV-2 and MS).This new system was applied to a specific new HSV-2 variant recently identified in HIV-1-infected patients originating from West Africa.Our results confirm that microsatellite polymorphism analysis is an accurate tool for studying the epidemiology of HSV-2 infections.© 2013, American Society for Microbiology.All Rights Reserved. Source

Adenis A.,Lille Catholic University | Adenis A.,Center Oscar Lambret | de la Fouchardiere C.,Center Leon Berard | Paule B.,Paul Brousse University Hospital | And 10 more authors.
BMC Cancer | Year: 2016

Background: Randomized trials have shown a survival benefit for regorafenib over placebo in patients with metastatic colorectal cancer (mCRC) that progressed after standard therapies. We evaluated survival and safety outcomes in patients treated with regorafenib in a real-life setting. Methods: REBECCA is a cohort study nested within a compassionate use program designed to evaluate survival, safety, and potential prognostic factors for outcome associated with regorafenib in patients with mCRC refractory to standard therapies. Treatment effects according to various patient and tumour characteristics were evaluated using univariate and multivariate Cox proportional hazards regression models. Results: Of 1178 patients in the compassionate use program, 654 were in the full analysis set. Median follow-up was 16.5 months. Median survival was 5.6 months. The 12-month survival rate was 22 %. Survival was independently and unfavourably affected by the following variables: poor performance status, short time from initial diagnosis of metastases to the start of regorafenib, low initial regorafenib dose, >3 metastatic sites, presence of liver metastases, and KRAS mutations. We identified prognostic groups of patients with low, intermediate, and high risk of death, with a median survival of 9.2, 5.2, and 2.5 months, respectively. Five-hundred-twenty-four patients (80 %) experienced at least one regorafenib-related adverse event, most commonly, fatigue, hand-foot skin reaction, diarrhea, anorexia, arterial hypertension, and mucositis. Conclusion: The safety and efficacy profile of regorafenib in REBECCA are similar to those in randomized trials. Our prognostic model identified subgroups of mCRC patients who derived a minimal and maximum benefit from regorafenib. Trial registration: Clinicaltrials.gov NCT02310477. © 2016 The Author(s). Source

Corruble E.,French Institute of Health and Medical Research | Barry C.,French Institute of Health and Medical Research | Varescon I.,University Paris - Sud | Castaing D.,Paul Brousse University Hospital | And 2 more authors.
Journal of Psychosomatic Research | Year: 2012

Objective: The transplanted organ is a key element of the recipient's daily life. But its representations are neither spontaneously expressed by patients, nor taken into account by transplantation professionals. Our objective was to assess specifically the transplanted organ representations in liver transplant recipients. Methods: In a prospective cohort study, 134 liver transplanted (LT) patients were assessed using the Transplanted Organ Questionnaire (TOQ), a new specifically designed questionnaire, fulfilled 3, 6, 12, 24, and 36. months post-LT. Results: The TOQ comprised three dimensions, explaining 44% of the total variance: Donor (21.3%) measuring the recipients' concerns about the donor, Positive attitude towards the transplant (13.4%), and Psychological Rejection (9.3%), measuring a lack of incorporation of the transplant. These three dimensions have a high internal consistency (Cronbach alpha: 0.91, 0.76 and 0.56) and are stable over time. Older recipients had more concern about the Donor than younger ones. As compared to other medical primary diagnoses, viral hepatitis was associated with higher scores on the subscales Positive attitude towards the transplant and Psychological Rejection. Interestingly, Psychological rejection predicted increased long term risk of death (HR, 1.20; 95% CI, 1.01-1.44, P= .046) under multivariate Cox analyses, independently from other variables. Conclusion: The transplanted organ representations as specifically assessed by the Transplanted Organ Questionnaire (TOQ) are relevant in liver transplant recipients. Interventions based on the transplant representations after LT should be assessed in further studies. Indeed, preventing psychological rejection of the transplanted organ and facilitating its psychological incorporation may decrease long term mortality after LT. © 2012 Elsevier Inc. Source

Eisinger F.,French Institute of Health and Medical Research | Morere J.-F.,Paul Brousse University Hospital | Pivot X.,Jean Minjoz University Hospital | Grange F.,Robert Debre University Hospital | And 3 more authors.
Journal of the European Academy of Dermatology and Venereology | Year: 2015

Objectives The incidence of skin cancers, melanoma in particular, is increasing rapidly. Consequently, specific recommendations for sun-protection measures now exist. This survey set out to assess the compliance of the general population with these guidelines. Methods The French nationwide observational survey, EDIFICE Melanoma, was conducted (28 September to 20 October 2011) through phone interviews of a representative sample of 1502 subjects aged ≥ 18 years, using the quota method. Sun-protection was defined as frequent or systematic use of clothes or sunscreen. The group of individuals who declared exposure to the sun (N = 1172) was subdivided: risk-takers (N = 442), and those who used sun protection (N = 730). Results Risk-takers were significantly more often male (62% vs. 44%, P < 0.01), had a lower level of education (40% vs. 26%, P < 0.01), lower incomes (2587 euros vs. 2948 euros/month) and were more often smokers (42% vs. 31%, P < 0.01). In contrast, age, marital status and use of sunbeds were not significantly different between the two groups. Interestingly, risk-takers had less risk factors for melanoma. However, they were less well-informed about high-risk exposure and optimal use of sunscreen. Sun-protection measures for their children were less stringent than those of the group who used sun protection: systematic/frequent use of sunglasses (42% vs. 59%, P < 0.01), systematic use of sunscreen (77% vs. 86%, P < 0.01), and frequent renewal (69% vs. 82%, P < 0.01), high sun protection factors (SPF) (46% vs. 56%, P < 0.01), use of clothing (84% vs. 92%, P < 0.01) and hats (88% vs. 94%, P < 0.01). Conclusions Risk-takers are characterized by a lesser understanding of sun-protection measures and behaviours. Their children benefit less from protective measures than those of people who use sun protection themselves. Improved understanding may well improve behaviours; one can therefore legitimately predict a considerable impact on parents' attitude to their own protection and that of their children. © 2015 European Academy of Dermatology and Venereology. Source

Paule B.,Paul Brousse University Hospital | Castagne V.,Paul Brousse University Hospital | Picard V.,University Paris - Sud | Saffroy R.,French Institute of Health and Medical Research | And 5 more authors.
Medical Oncology | Year: 2010

The aim of the study was to evaluate the influence of the MDR1 C3435T polymorphism on the therapeutic response in 23 patients treated with cetuximab plus irinotecan for irinotecan refractory liver metastatic colorectal cancer considering their KRAS status. Indeed, irinotecan and its active metabolite (SN-38) are both substrates of P-glycoprotein (P-gp) encoded by MDR1. Patients received cetuximab and irinotecan up to progression. The overall survival was 55% at 10 months. Overall, four patients had an undetermined KRAS status and two patients with mutated KRAS were in progression disease. The response to treatment was observed after 3 months among the 17 wild-type KRAS patients. Two patients presented a progressive disease (1 TT and 1 CT), eight patients had a stable disease (5 CC and 3CT) and five patients had a partial response (3 CC and 2 CT). Importantly, 2 patients (2 TT) were in complete response and still alive 5 years after starting the treatment, which suggests that the combination of wild-type KRAS and MDR1 3435 TT may be a factor of good prognosis. These results suggest that EGFR inhibition by cetuximab may overcome this irinotecan resistance by abrogating drug efflux depending on MDR1 3435 polymorphism. Among patients resistant to irinotecan, it is still possible to use the association of cetuximab plus irinotecan to obtain a complete resection of hepatic metastases that is necessary to improve their survival. © Humana Press Inc. 2009. Source

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