Sacconi S.,French National Center for Scientific Research |
Bocquet J.D.,Pierre Zobda Quitman Hospital |
Chanalet S.,Pasteur Hospital |
Salviati L.,University of Padua |
Desnuelle C.,French National Center for Scientific Research
Journal of Neurology | Year: 2010
Cerebral aneurysms and arteropathies causing severe cerebrovascular events have been reported as rare complications in patients with late-onset Pompe disease. We investigated the frequency of cerebrovascular anomalies in six patients with late-onset Pompe disease followed at our institution. Clinical data collection and magnetic resonance angiography were performed as part of routine annual examinations. Four out of six patients had brain vascular anomalies including dolichoectasia of the basilar artery and ectasia of internal carotids. These patients also complained of gastrointestinal symptoms (chronic constipation and gastrointestinal reflux). Two patients had clinical signs related to the arteriopathy, including partial paralysis of the third cranial nerve and transient ischemic attacks. At 1 year follow-up, enzyme replacement therapy did not modify the size of cerebral vessels, but patients reported a marked improvement of intestinal symptoms. In conclusion, neurologists should be aware that intracranial artery abnormalities are not infrequent in patients with lateonset Pompe disease, and they should be specifically investigated in the presence of unexplained CNS symptoms. © Springer-Verlag 2010.
Pallud J.,Sainte Anne Hospital |
Pallud J.,University of Paris Descartes |
Taillandier L.,Nancy Neurological Hospital Nancy |
Capelle L.,Pitie Salpetriere Hospital |
And 7 more authors.
Neurosurgery | Year: 2012
Supratentorial hemispheric diffuse low-grade gliomas (LGGs), ie, World Health Organization grade II gliomas, are a heterogeneous group of tumors. During their natural course, LGGs tend to progress to a higher grade of malignancy, leading to neurological disability and ultimately to death. In this review, we will show, that during their low-grade period, these tumors exhibit systematically a spontaneous and continuous radiological growth, whatever their histological subtypes. The radiological tumor growth is easily quantified by measuring the evolution of the equivalent tumor diameter (calculated from the tumor volume), obtaining the velocity of diametric expansion (VDE). The spontaneous VDE of LGGs varies markedly with an average VDE of about 4 mm/year. It depends on intrinsic factors (1p19q codeletion status, P53 overexpression status) and can be modified by extrinsic factors (pregnancy). The spontaneous VDE carries a strong prognostic significance regarding progression-free and overall survivals. As a consequence, VDE should be integrated along with the other "static" parameters (multimodal imaging, histological and molecular analyses) in the initial investigations. In addition, the assessment of VDE obtained before, during, and after a particular oncological treatment helps in analyzing their effects on LGGs on an individual basis, helping to guide the decision making. Copyright © 2012 by the Congress of Neurological Surgeons.
Pop D.,Pasteur Hospital |
Nadeemy A.S.,Pasteur Hospital |
Nadeemy A.S.,Kabul University |
Venissac N.,Pasteur Hospital |
Mouroux J.,Pasteur Hospital
Interactive Cardiovascular and Thoracic Surgery | Year: 2011
The postpneumonectomy bronchopleural fistula (BPF) remains a difficult challenge for the thoracic surgeon. We report the case of a very late-onset (60 years) left BPF managed by video-assisted mediastinoscopy discussing the direct consequences of this complication in the postpneumonectomy period. © 2011 Published by European Association for Cardio-Thoracic Surgery. All rights reserved.
Abreu D.,Pasteur Hospital
BMJ case reports | Year: 2011
Prostatic abscess is rare. Its potentially serious course requires a high level of clinical suspicion and prompt and effective treatment. The causative germs are usually either enterobacteria or Enterococcus. The authors highlight the importance of considering epidemiological and clinical aspects in the early diagnosis and treatment. Prostatic abscess due to community-acquired methicillin resistant Staphylococcus has three typical characteristics: skin entry point, periprostatic compromise, and anaemia and low prothrombin.
Chevallier D.,Pasteur Hospital |
Chevallier D.,University of Nice Sophia Antipolis |
Carette D.,University of Paris Descartes |
Carette D.,University of Versailles |
And 5 more authors.
Cellular and Molecular Life Sciences | Year: 2013
Gap junction channels link cytoplasms of adjacent cells. Connexins, their constitutive proteins, are essential in cell homeostasis and are implicated in numerous physiological processes. Spermatogenesis is a sophisticated model of germ cell proliferation, differentiation, survival, and apoptosis, in which a connexin isotype, connexin 43, plays a crucial role as evidenced by genomic approaches based on gene deletion. The balance between cell proliferation/ differentiation/apoptosis is a prerequisite for maintaining levels of spermatozoa essential for fertility and for limiting anarchic cell proliferation, a major risk of testis tumor. The present review highlights the emerging role of connexins in testis pathogenesis, focusing specifically on two intimately interconnected human testicular diseases (azoospermia with impaired spermatogenesis and testicular germ cell tumors), whose incidence increased during the last decades. This work proposes connexin 43 as a potential cancer diagnostic and prognostic marker, as well as a promising therapeutic target for testicular diseases. © 2012 Springer Basel AG.
Discrepancies between FISH and immunohistochemistry for assessment of the ALK status are associated with ALK borderline-positive rearrangements or a high copy number: A potential major issue for anti-ALK therapeutic strategies
Ilie M.I.,Pasteur Hospital |
Ilie M.I.,University of Nice Sophia Antipolis |
Bence C.,Pasteur Hospital |
Hofman V.,Pasteur Hospital |
And 16 more authors.
Annals of Oncology | Year: 2015
Background: Patients with advanced lung adenocarcinomas expressing ALK rearrangements are highly responsive to crizotinib, a dual ALK/c-MET inhibitor. Immunohistochemistry (IHC) is an easy clinically and routinely applicable costeffective assay for ALK, c-MET and ROS1 protein expression for potential treatment with crizotinib. The purpose of this study was to evaluate the percentage and the pattern of ALK-rearranged cells, the variation in the native ALK copy number, as well as ALK, c-MET and ROS1 protein expression, and their significance on outcome of crizotinib-treated lung adenocarcinoma patients. Patients and methods: Consecutive lung adenocarcinoma specimens (n = 176) 'double-negative' (wild-type EGFR and KRAS) were tested for ALK rearrangements/copy number alterations and for ALK, c-MET and ROS1 protein expression using automated standardized protocols. Preliminary data on the outcome of crizotinib-treated patients were recorded. Results: FISH analysis identified 26/176 (15%) cases with ALK rearrangements. Seven cases had discordant results between the ALK FISH and IHC. Five cases with discordant FISH-positive/IHC-negative revealed FISH 'borderline' positivity (15%-20%). Three cases overexpressed c-MET and responded to crizotinib, and two cases with ALK-'borderline' rearranged cells only, not associated with c-MET expression, progressed under crizotinib. Two cases with discordant FISH-negative/IHC-positive revealed ALK gene amplification without associated c-MET or ROS1 protein expression. Conclusions: The discrepancies observed between the IHC and FISH data revealed unexpected biological events, rather than technical issues, which potentially can have a strong impact on the therapeutic strategy with crizotinib. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.
Carette D.,University of Paris Descartes |
Gilleron J.,French Institute of Health and Medical Research |
Gilleron J.,University of Nice Sophia Antipolis |
Chevallier D.,Pasteur Hospital |
And 4 more authors.
Biochimie | Year: 2014
Gap junction protein connexins (Cxs) play essential roles in cell homeostasis, growth, differentiation and death. Therefore, Cx dysfunction has been associated with many diseases and with tumor development. Cxs control cell apoptosis through different molecular mechanisms. First, gap junction channels classically facilitate the influx and flux of apoptotic signals between adjacent cells and hemichannels between the intracellular and extracellular environments. Second, recent studies demonstrate that Cx proteins, independently from their functional role through channels or hemichannels and in conjunction with their intracytoplasmic localization, may act as signaling effectors able to activate the canonical mitochondrial apoptotic pathway. In the present review, we dissected both functions of Cx in apoptosis, providing new avenues for apoptosis-mediated cancer therapy. © 2013 Elsevier Masson SAS. All rights reserved.
Hofman P.,Hospital Integrated Tumor Biobank |
Hofman P.,French Institute of Health and Medical Research |
Hofman P.,Pasteur Hospital |
Brechot C.,Institute Pasteur Paris |
And 3 more authors.
Virchows Archiv | Year: 2014
Access to human bioresources is essential to the understanding of human diseases and to the discovery of new biomarkers aimed at improving the diagnosis, prognosis, and the predictive response of patients to treatments. The use of biospecimens is strictly controlled by ethical assessment, which complies with the laws of the country. These laws regulate the partnerships between the biobanks and industrial actors. However, private-public partnerships (PPP) can be limiting for several reasons, which can hamper the discovery of new biological tests and new active molecules targeted to human diseases. The bottlenecks and roadblocks in establishing these partnerships include: poor organization of the biobank in setting up PPP, evaluation of the cost of human samples, the absence of experience on the public side in setting up contracts with industry, and the fact that public and private partners may not share the same objectives. However, it is critical, in particular for academic biobanks, to establish strong PPP to accelerate translational research for the benefits of patients, and to allow the sustainability of the biobank. The purpose of this review is to discuss the main bottlenecks and roadblocks that can hamper the establishment of PPP based on solid and trusting relationships. © 2013 Springer-Verlag Berlin Heidelberg.
Crouzet S.,Edouard Herriot Hospital |
Crouzet S.,University of Lyon |
Rebillard X.,Beau Soleil Clinic |
Chevallier D.,Pasteur Hospital |
And 8 more authors.
European Urology | Year: 2010
Background: High-intensity focused ultrasound (HIFU) is an emerging treatment for select patients with localized prostate cancer (PCa). Objectives: To report the oncologic outcome of HIFU as a primary care option for localized prostate cancer from a multicenter database. Design, setting, and participants: Patients with localized PCa treated with curative intent and presenting at least a 2-yr follow-up from February 1993 were considered in this study. Previously irradiated patients were excluded from this analysis. In case of any residual or recurrent PCa, patients were systematically offered a second session. Kaplan-Meier analysis was performed to determine disease-free survival rates (DFSR). Measurements: Prostate-specific antigen (PSA), clinical stage, and pathologic results were measured pre- and post-HIFU. Results and limitations: A total of 803 patients from six urologic departments met the inclusion criteria. Stratification according to d'Amico's risk group was low, intermediate, and high in 40.2%, 46.3%, and 13.5% of patients, respectively. Mean follow-up was 42 ± 33 mo. Mean PSA nadir was 1.0 ± 2.8 ng/ml with 54.3% reaching a nadir of ≤0.3 ng/ml. Control biopsies were negative in 85% of cases. The overall and cancer-specific survival rates at 8 yr were 89% and 99%, respectively. The metastasis-free survival rate at 8 yr was 97%. Initial PSA value and Gleason score value significantly influence the DFSR. The 5- and 7-yr biochemical-free survival rates (Phoenix criteria) were 83-75%, 72-63%, and 68-62% (p = 0.03) and the additional treatment-free survival rates were 84-79%, 68-61%, and 52-54% (p < 0.001) for low-, intermediate-, and high-risk patients, respectively. PSA nadir was a major predictive factor for HIFU success: negative biopsies, stable PSA, and no additional therapy. Conclusions: Local control and DFSR achieved with HIFU were similar to those expected with conformal external-beam radiation therapy (EBRT). The excellent cancer-specific survival rate is also explained by the possibility to repeat HIFU and use salvage EBRT. © 2010 European Association of Urology.
Vassallo M.,University of Nice Sophia Antipolis |
Vassallo M.,Cannes General Hospital |
Durant J.,University of Nice Sophia Antipolis |
Biscay V.,University of Nice Sophia Antipolis |
And 9 more authors.
AIDS | Year: 2014
OBJECTIVE:: To assess changes over time in neuropsychological test results (NPr) and risk factors among a regularly followed HIV-infected patient population. METHODS:: Prospective cohort of HIV-infected patients randomly selected to undergo neuropsychological follow-up. Test score was adjusted for age, sex and education. Patients were divided into five groups: normal tests, neuropsychological deficit (one impaired cognitive domain), asymptomatic neurocognitive disorders (ANIs), mild neurocognitive disorders (MNDs) and HIV-associated dementia (HAD). Demographic and background parameters including CSF drug concentration penetration effectiveness (CPE) score 2010 were recorded. Changes in NPr and associated risk factors were analyzed. RESULTS:: Two hundred and fifty-six patients underwent neuropsychological tests and 96 accepted follow-up approximately 2 years later. The groups were comparable. Upon neuropsychological retesting, six patients improved, 31 worsened and 59 were stable. The proportion of patients with HIV-associated neurocognitive disorders (HANDs) rose from 26 to 45%, with ANIs and MNDs still mostly represented. Most patients initially diagnosed with HANDs remained stable, five of 25 showed clinical improvement and three of 25 deteriorated. Of 33 patients with normal tests, four deteriorated, whereas 24 of 38 with initial neuropsychological deficit had poorer NPr, and contributed most of the new HAND cases. Patients with clinical deterioration had a lower CPE score both at inclusion (6.9 vs. 8.1; PS=S0.005) and at the end of follow-up (7.2 vs. 7.8; PS=S0.08) than those with improved or stable performance. This was confirmed by multivariate analysis. CONCLUSION:: Patients with higher CPE scores upon inclusion and at the end of follow-up were at lower risk of clinical worsening, suggesting that combination antiretroviral therapy with better CSF penetration could protect against cognitive deterioration. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.