Assistance Publique Hopitaux de Marseille AP HM

Hôpital-Camfrout, France

Assistance Publique Hopitaux de Marseille AP HM

Hôpital-Camfrout, France

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Chabannon C.,Institute Paoli Calmettes | Honstettre A.,Institute Paoli Calmettes | Daufresne L.-M.,Institute Paoli Calmettes | Martin P.-M.,Assistance Publique hopitaux de Marseille AP HM | And 14 more authors.
Bulletin du Cancer | Year: 2010

Biobanks in general, and specifically tumour banks, are considered as essential tools for the development of translational and clinical research in biology and oncology. Biobank tasks include the collection and preservation of biological samples, and their association with information that will be essential for further scientific use ("annotations" that allow for the "qualification" of biological samples in biological resource). A collection is made of a series of biological resource that are representative of a homogeneous group of individuals or patients that are defined on the basis of clinical or biological information. Collections are used by scientists that are aware of their existence. In the absence of a published catalogue, this awareness is most often limited to research teams that are geographically close, or to investigators who already established collaborative projects with medical teams within the hospital that operates the tumour bank. Publications of catalogues, especially digitalized and online catalogues, should foster the development of high-level, large-scale and multicentric scientific projects. In addition, tumour banks will formalize rules that allow publication of collections, and upstream, rules that are used to qualify biological samples in biological resource: this should translate in an improved overall quality of samples and annotations. Tumour bank catalogues remain relatively few; however, some recent achievements established the "proof of concept" and already raise questions regarding rules for publication. It will be important to demonstrate that these high expectations translate into measurable benefits. ©John Libbey Eurotext.


Daly A.F.,University of Liège | Yuan B.,Baylor College of Medicine | Fina F.,Assistance Publique Hopitaux de Marseille AP HM | Fina F.,Aix - Marseille University | And 28 more authors.
Endocrine-Related Cancer | Year: 2016

Somatic mosaicism has been implicated as a causative mechanism in a number of genetic and genomic disorders. X-linked acrogigantism (XLAG)syndrome is a recently characterized genomic form of pediatric gigantism due to aggressive pituitary tumors that is caused by submicroscopic chromosome Xq26.3 duplications that include GPR101. We studied XLAG syndrome patients (n = 18)to determine if somatic mosaicism contributed to the genomic pathophysiology. Eighteen subjects with XLAG syndrome caused by Xq26.3 duplications were identified using high-definition array comparative genomic hybridization (HD-aCGH). We noted that males with XLAG had a decreased log2 ratio (LR)compared with expected values, suggesting potential mosaicism, whereas females showed no such decrease. Compared with familial male XLAG cases, sporadic males had more marked evidence for mosaicism, with levels of Xq26.3 duplication between 16.1 and 53.8% These characteristics were replicated using a novel, personalized breakpoint junction-specific quantification droplet digital polymerase chain reaction (ddPCR)technique. Using a separate ddPCR technique, we studied the feasibility of identifying XLAG syndrome cases in a distinct patient population of 64 unrelated subjects with acromegaly/gigantism, and identified one female gigantism patient who had had increased copy number variation (CNV)threshold for GPR101 that was subsequently diagnosed as having XLAG syndrome on HD-aCGH. Employing a combination of HD-aCGH and novel ddPCR approaches, we have demonstrated, for the first time, that XLAG syndrome can be caused by variable degrees of somatic mosaicism for duplications at chromosome Xq26.3. Somatic mosaicism was shown to occur in sporadic males but not in females with XLAG syndrome, although the clinical characteristics of the disease were similarly severe in both sexes. © 2016 Society for Endocrinology.


Pontier J.-M.,British Petroleum | Buzzacott P.,University of Western Brittany | Buzzacott P.,University of Western Australia | Nastorg J.,Assistance Publique Hopitaux de Marseille AP HM | And 2 more authors.
Nitric Oxide - Biology and Chemistry | Year: 2014

Introduction Previous studies have highlighted a decreased exhaled nitric oxide concentration (FE NO) in divers after hyperbaric exposure in a dry chamber or following a wet dive. The underlying mechanisms of this decrease remain however unknown. The aim of this study was to quantify the separate effects of submersion, hyperbaric hyperoxia exposure and decompression-induced bubble formation on FE NO after a wet dive. Methods Healthy experienced divers (n = 31) were assigned to either (i) a group making a scuba-air dive (Air dive), (ii) a group with a shallow oxygen dive protocol (Oxygen dive) or (iii) a group making a deep dive breathing a trimix gas mixture (deep-dive). Bubble signals were graded with the KISS score. Before and after each dive FE NO values were measured using a hand-held electrochemical analyzer. Results There was no change in post-dive values of FE NO values (expressed in ppb = parts per billion) in the Air dive group (15.1 ± 3.6 ppb vs. 14.3 ± 4.7 ppb, n = 9, p = 0.32). There was a significant decrease in post-dive values of FE NO in the Oxygen dive group (15.6 ± 6 ppb vs. 11.7 ± 4.7 ppb, n = 9, p = 0.009). There was an even more pronounced decrease in the deep dive group (16.4 ± 6.6 ppb vs. 9.4 ± 3.5 ppb, n = 13, p < 0.001) and a significant correlation between KISS bubble score >0 (n = 13) and percentage decrease in post-dive FE NO values (r = -0.53, p = 0.03). Discussion Submersion and hyperbaric hyperoxia exposure cannot account entirely for these results suggesting the possibility that, in combination, one effect magnifies the other. A main finding of the present study is a significant relationship between reduction in exhaled NO concentration and dive-induced bubble formation. We postulate that exhaled NO concentration could be a useful index of decompression severity in healthy human divers. © 2014 Published by Elsevier Inc.


PubMed | British Petroleum, Assistance Publique Hopitaux de Marseille AP HM, University of Western Australia, University of Paris Descartes and University of Western Brittany
Type: | Journal: Nitric oxide : biology and chemistry | Year: 2014

Previous studies have highlighted a decreased exhaled nitric oxide concentration (FE NO) in divers after hyperbaric exposure in a dry chamber or following a wet dive. The underlying mechanisms of this decrease remain however unknown. The aim of this study was to quantify the separate effects of submersion, hyperbaric hyperoxia exposure and decompression-induced bubble formation on FE NO after a wet dive.Healthy experienced divers (n=31) were assigned to either (i) a group making a scuba-air dive (Air dive), (ii) a group with a shallow oxygen dive protocol (Oxygen dive) or (iii) a group making a deep dive breathing a trimix gas mixture (deep-dive). Bubble signals were graded with the KISS score. Before and after each dive FE NO values were measured using a hand-held electrochemical analyzer.There was no change in post-dive values of FE NO values (expressed in ppb=parts per billion) in the Air dive group (15.1 3.6 ppb vs. 14.3 4.7 ppb, n=9, p=0.32). There was a significant decrease in post-dive values of FE NO in the Oxygen dive group (15.6 6 ppb vs. 11.7 4.7 ppb, n=9, p=0.009). There was an even more pronounced decrease in the deep dive group (16.4 6.6 ppb vs. 9.4 3.5 ppb, n=13, p<0.001) and a significant correlation between KISS bubble score >0 (n=13) and percentage decrease in post-dive FE NO values (r=-0.53, p=0.03).Submersion and hyperbaric hyperoxia exposure cannot account entirely for these results suggesting the possibility that, in combination, one effect magnifies the other. A main finding of the present study is a significant relationship between reduction in exhaled NO concentration and dive-induced bubble formation. We postulate that exhaled NO concentration could be a useful index of decompression severity in healthy human divers.


Albarel F.,Assistance Publique Hopitaux de Marseille AP HM | Albarel F.,Aix - Marseille University | Gaudy C.,Aix - Marseille University | Castinetti F.,Assistance Publique Hopitaux de Marseille AP HM | And 9 more authors.
European Journal of Endocrinology | Year: 2015

Objective: Few data are published on the long-term follow-up of ipilimumab-induced hypophysitis, a cytotoxic T-lymphocyte antigen 4 antibody. We characterized hypophysitis in terms of clinical signs, endocrinological profile, and imaging at diagnosis and during a long-term follow-up. Design and patients: Fifteen patients, treated for malignant melanoma and who presented ipilimumab-induced hypophysitis, were observed between June 2006 and August 2012 in Timone Hospital, Marseille. Methods: Symptoms, pituitary function, and pituitary imaging at diagnosis of hypophysitis and during the follow-up were recorded. Results: Of 131 patients treated with ipilimumab or a placebo, 15 patients (10 mg/kg in 11/15) presented with hypophysitis (R11.5%) at 9.5G5.9 weeks (meanGS.D.) after treatment start, occurring in 66% after the third infusion. The main initial symptoms were headache (n=13) and asthenia (n=11). All patients but one had at least one hormonal defect: thyrotroph (n=13), gonadotroph (n=12), or corticotroph (n=11) deficiencies. None had diabetes insipidus. Pituitary imaging showed a moderately enlarged gland in 12 patients. Clinical symptoms improved rapidly on high-dose glucocorticoids (n=11) or physiological replacement doses (n=4). At the end of follow-up (median 33.6 months, range 7-53.5), corticotroph deficiency remained in 13 patients, 11 recovered thyrotroph and ten gonadotroph functions. Pituitary imaging remained abnormal in 11 patients. Conclusion: Ipilimumab-induced hypophysitis is a common side-effect with frequent hormonal deficiencies at diagnosis. Usually, hormonal deficiencies improved, except for corticotroph function. Patients receiving these immunomodulatory therapies should be closely monitored especially by systematic baseline hormone measurements after the third infusion and remain at a risk of adrenal insufficiency in the long-term. © 2015 European Society of Endocrinology Printed in Great Britain.


Torres L.,Aix - Marseille University | Frapard C.,Aix - Marseille University | Daumas A.,Assistance publique Hopitaux de Marseille AP HM | Guibert N.,Aix - Marseille University | And 4 more authors.
Presse Medicale | Year: 2016

Objective: The primary objective of this study was to determine the reasons given by women who have changed or suspended their contraceptive method in 2013. What influence had the 3rd and 4th generation estroprogestatives (EP) French controversy and advices from doctors? Did they notice any consequences of the controversy on their lifestyle? Did they feel an impact on their behavior to health professionals? Methods: A study was conducted on women of childbearing age. Data collection took place between November 4 and December 16, 2013. The included subjects were between 18 and 55 years old females. Subjects were surveyed through an anonymous self-administered questionnaire distributed through pharmacies. The protocol called for the construction of clusters of subjects by having heard about, or not, of the controversy. Patients reporting having heard about the controversy have formed the "exposed" group while the others have formed the "unexposed" group. We compared two parameters between these two groups: the rate of subjects who reported having modified or suspended their contraceptive method in 2013 on one hand, and the rate of subjects who reported having made a change in their contraceptive method without or against advices from a doctor on the other hand. Results: The sample included 988 subjects. The average age was 34 years. The level of exposure to media debates was 86.5%. Of the respondents, 19.8% were under 3rd or 4th generation EP in 2012, thus directly involved in the discussions and affected by health recommendations. Of the patients, 38.5% reported having changed their contraception in 2013. In these women, when they confirmed having heard about the controversy, 40.1% of them claimed to have conducted this process without or against advices from a doctor. This number dropped to 18.2% for those who had not heard of it. Media coverage of the 3rd and 4th generation EP vascular risk was not mentioned more by patients who suspended all medical contraceptive method than it was by patients who simply changed their method. In all, 52.1% of women who completely stopped their contraception indicated that this choice was at least partly due to a change in their sexuality or reproductive life. This reason was evoked only in 19.0% of women who have simply made a change of contraceptive method. Among the views of women, the EP controversy was one of the reasons for a change of contraception method in 41.8% of cases, while advices from a doctor did play a role in 19.9% of cases. One has seen a decline of 11.0% of oral contraception between 2012 and 2013, almost superimposed on that of oral 3rd and 4th generation EP (10.6%). However, the use of 1st and 2nd generation EP stagnated: their increase was 0.4%. Beyond any change of contraceptive method, 66.9% of women expressed the absence of any impact of the controversy on their behavior. Of the women, 6.1% showed a loss of confidence in health professionals. Conclusion: We have shown how patients who stopped or modified their contraception method during 2013 placed the controversy influence in the forefront of the reasons for their decision. Although a medical reason has been widely quoted, only one in five felt that the advice of her doctor had clearly contributed to her choice. The influence of the media seemed to encroach on the doctor-patient relationship, which is fundamental to the quality of healthcare in the long term. Ce qui était connu: •Pas de report des utilisatrices d'EP de 3e et 4e génération vers les 1re et 2e génération.•Impact négatif de la controverse sur le taux d'utilisation des méthodes orales. Ce qu'apporte l'article: •Très forte pénétrance des campagnes médiatiques dans l'opinion publique.•Les représentations des femmes placent le rôle des médias avant celui des professionnels de santé. © 2016 Elsevier Masson SAS.


Leca M.,Assistance Publique Hopitaux de Marseille AP HM | Bornet C.,Assistance Publique Hopitaux de Marseille AP HM | Montana M.,Assistance Publique Hopitaux de Marseille AP HM | Montana M.,Aix - Marseille University | And 2 more authors.
Pathologie Biologie | Year: 2015

Neisseria meningitidis infections are a major public health problem worldwide. Although conventional approaches have not led to development of a serogroup B meningococcal vaccine, a new technique based on genome sequencing has created new perspectives. Recently, a universal serogroup B meningococcal vaccine, Bexsero®, was licensed in Europe, Australia and United States, following several clinical studies demonstrating its immunogenicity and safety. Availability of this vaccine could contribute positively to human health, by significantly reducing the incidence of meningococcal infections. However, unfavorable cost-effectiveness analysis means that routine vaccination is not currently recommended. Another serogroup meningococcal vaccine, Trumemba®, was also recently licensed in United States. Like any drug, Bexsero® and Trumemba® will require close observation to assess their impact on meningococcal epidemiology. © 2015 Elsevier Masson SAS.


Jarrot P.-A.,Assistance Publique Hopitaux de Marseille AP HM | Jarrot P.-A.,Aix - Marseille University | Kaplanski G.,Assistance Publique Hopitaux de Marseille AP HM | Kaplanski G.,Aix - Marseille University
Autoimmunity Reviews | Year: 2016

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) constitutes a group of rare diseases characterized by necrotizing inflammation of small blood vessels and the presence of ANCA. Although these autoantibodies were initially used to classify pauci-immune vasculitis, increasing clinical and experimental evidence now supports their pathogenic role, mainly through ANCA-induced activation of primed neutrophils and monocytes leading to destructive vascular necrosis. The mechanisms of ANCA generation remain however unclear. Neutrophils play a central role in the pathophysiological process of AAV since they are both effector cells responsible for endothelial damage and targets of autoimmunity. Another role of neutrophils is due to their ability to generate neutrophil extracellular traps, which support the presentation of ANCA autoantigens, could break immune tolerance and induce autoantibody generation. Alternatively, the ANCA autoimmune response is facilitated by insufficient T-cell and B-cell regulation, and the role of complement alternative pathway has recently been emphasized. This review summarizes the main pathogenesis concepts of AAV as well as the putative mechanisms for the origin of ANCA autoimmune response. © 2016 Elsevier B.V.


PubMed | Aix - Marseille University and Assistance Publique Hopitaux de Marseille AP HM
Type: Journal Article | Journal: Environmental monitoring and assessment | Year: 2017

Environmental monitoring is usually conducted by surface sampling to detect and quantify the presence of cytotoxic drugs after their reconstitution and administration. This technique reveals the origins of residual contamination and is an important component in order to protect healthcare workers from the potential risk of occupational exposure. The aim of this work is to compare various techniques and results of surface sampling for cytotoxics. For each technique, sample processing methods and their analysis were compared from literature data. Sampling is often performed by the wiping technique. After treatment, various single or multicompound technical analyses are used, in particular liquid or gas chromatography involving different detection methods: ultraviolet, mass spectrometry, plasma torch, and voltammetry. Some methods are validated to ensure reliability. Despite published guidelines and the use of isolator technology for the preparation of cytotoxic drugs, workplace contamination persists, leading to chemotherapeutic agents exposure of healthcare workers. Efforts need to be maintained with particular emphasis on harmonization and on determining alert level for cytotoxic contamination.


PubMed | Aix - Marseille University and Assistance publique Hopitaux de Marseille AP HM
Type: Journal Article | Journal: Presse medicale (Paris, France : 1983) | Year: 2016

The primary objective of this study was to determine the reasons given by women who have changed or suspended their contraceptive method in 2013. What influence had the 3rd and 4th generation estroprogestatives (EP) French controversy and advices from doctors? Did they notice any consequences of the controversy on their lifestyle? Did they feel an impact on their behavior to health professionals?A study was conducted on women of childbearing age. Data collection took place between November 4 and December 16, 2013. The included subjects were between 18 and 55 years old females. Subjects were surveyed through an anonymous self-administered questionnaire distributed through pharmacies. The protocol called for the construction of clusters of subjects by having heard about, or not, of the controversy. Patients reporting having heard about the controversy have formed the exposed group while the others have formed the unexposed group. We compared two parameters between these two groups: the rate of subjects who reported having modified or suspended their contraceptive method in 2013 on one hand, and the rate of subjects who reported having made a change in their contraceptive method without or against advices from a doctor on the other hand.The sample included 988 subjects. The average age was 34 years. The level of exposure to media debates was 86.5%. Of the respondents, 19.8% were under 3rd or 4th generation EP in 2012, thus directly involved in the discussions and affected by health recommendations. Of the patients, 38.5% reported having changed their contraception in 2013. In these women, when they confirmed having heard about the controversy, 40.1% of them claimed to have conducted this process without or against advices from a doctor. This number dropped to 18.2% for those who had not heard of it. Media coverage of the 3rd and 4th generation EP vascular risk was not mentioned more by patients who suspended all medical contraceptive method than it was by patients who simply changed their method. In all, 52.1% of women who completely stopped their contraception indicated that this choice was at least partly due to a change in their sexuality or reproductive life. This reason was evoked only in 19.0% of women who have simply made a change of contraceptive method. Among the views of women, the EP controversy was one of the reasons for a change of contraception method in 41.8% of cases, while advices from a doctor did play a role in 19.9% of cases. One has seen a decline of 11.0% of oral contraception between 2012 and 2013, almost superimposed on that of oral 3rd and 4th generation EP (10.6%). However, the use of 1st and 2nd generation EP stagnated: their increase was 0.4%. Beyond any change of contraceptive method, 66.9% of women expressed the absence of any impact of the controversy on their behavior. Of the women, 6.1% showed a loss of confidence in health professionals.We have shown how patients who stopped or modified their contraception method during 2013 placed the controversy influence in the forefront of the reasons for their decision. Although a medical reason has been widely quoted, only one in five felt that the advice of her doctor had clearly contributed to her choice. The influence of the media seemed to encroach on the doctor-patient relationship, which is fundamental to the quality of healthcare in the long term.

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