AP HM

Saint-Pierre-du-Chemin, France
Saint-Pierre-du-Chemin, France

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Karila L.,French Institute of Health and Medical Research | Roux P.,Aix - Marseille University | Rolland B.,Lille University Hospital Center | Benyamina A.,University Paris - Sud | And 3 more authors.
Current Pharmaceutical Design | Year: 2014

Cannabis remains the most commonly used and trafficked illicit drug in the world. Its use is largely concentrated among young people (15- to 34-year-olds). There is a variety of cannabis use patterns, ranging from experimental use to dependent use. Men are more likely than women to report both early initiation and frequent use of cannabis. Due to the high prevalence of cannabis use, the impact of cannabis on public health may be significant. A range of acute and chronic health problems associated with cannabis use has been identified. Cannabis can frequently have negative effects in its users, which may be amplified by certain demographic and/or psychosocial factors. Acute adverse effects include hyperemesis syndrome, impaired coordination and performance, anxiety, suicidal ideations/tendencies, and psychotic symptoms. Acute cannabis consumption is also associated with an increased risk of motor vehicle crashes, especially fatal collisions. Evidence indicates that frequent and prolonged use of cannabis can be detrimental to both mental and physical health. Chronic effects of cannabis use include mood disorders, exacerbation of psychotic disorders in vulnerable people, cannabis use disorders, withdrawal syndrome, neurocognitive impairments, cardiovascular and respiratory and other diseases. © 2014 Bentham Science Publishers.


Reyes-Botero G.,Groupe Hospitalier Pitie Salpetriere | Dehais C.,Groupe Hospitalier Pitie Salpetriere | Idbaih A.,Groupe Hospitalier Pitie Salpetriere | Idbaih A.,University Pierre and Marie Curie | And 14 more authors.
Neuro-Oncology | Year: 2014

BackgroundThe aim of this study was to correlate MRI features and molecular characteristics in anaplastic oligodendrogliomas (AOs).MethodsThe MRI characteristics of 50 AO patients enrolled in the French national network for high-grade oligodendroglial tumors were analyzed. The genomic profiles and IDH mutational statuses were assessed using high-resolution single-nucleotide polymorphism arrays and direct sequencing, respectively. The gene expression profiles of 25 1p/19q-codeleted AOs were studied on Affymetrix expression arrays.ResultsMost of the cases were frontal lobe contrast-enhanced tumors (52%), but the radiological presentations of these cases were heterogeneous, ranging from low-grade glioma-like aspects (26%) to glioblastoma-like aspects (22%). The 1p/19q codeletion (n = 39) was associated with locations in the frontal lobe (P =. 001), with heterogeneous intratumoral signal intensities (P =. 003) and with no or nonmeasurable contrast enhancements (P =. 01). The IDH wild-type AOs (n = 7) more frequently displayed ringlike contrast enhancements (P =. 03) and were more frequently located outside of the frontal lobe (P =. 01). However, no specific imaging pattern could be identified for the 1p/19q-codeleted AO or the IDH-mutated AO. Within the 1p/19q-codeleted AO, the contrast enhancement was associated with larger tumor volumes (P =. 001), chromosome 9p loss and CDKN2A loss (P =. 006), genomic instability (P =. 03), and angiogenesis-related gene expression (P <. 001), particularly for vascular endothelial growth factor A and angiopoietin 2.ConclusionIn AOs, the 1p/19q codeletion and the IDH mutation are associated with preferential (but not with specific) imaging characteristics. Within 1p/19q-codeleted AO, imaging heterogeneity is related to additional molecular alterations, especially chromosome 9p loss, which is associated with contrast enhancement and larger tumor volume. © 2013 © The Author(s) 2013. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.


Rossi P.,AP HM | Rossi P.,Institut Universitaire de France | Rossi P.,North Hospital | Tauzin L.,Center Hospitalier Territorial Of La Nouvelle Caldonie | And 4 more authors.
Journal of Adolescent Health | Year: 2011

Purpose Recent studies show that low birth weight infants are at a risk of increased arterial blood pressure (BP) in adulthood. This study aimed to distinguish the influence of low birth weight either as a result of fetal growth restriction or preterm birth on arterial properties in adolescents. Methods The effect of low birth weight on BP and arterial stiffness was examined among 90 adolescents aged 14 years who were either born at term with an appropriate birth weight for gestational age (controls, n = 41); born preterm with an appropriate birth weight for gestational age (n = 25); or born at term and small for gestational age (SGA) (n = 24). The pulse wave velocity between the carotid and radial arteries was measured to assess arterial stiffness. Results As compared with control subjects, adolescents born with low birth weight as a result of preterm birth were found to have increased systolic BP and carotidradial pulse wave velocity (117 ± 11 mm Hg vs. 123 ± 11 mm Hg, p = .04 and 7.0 ± .9 m/s vs. 7.7 ± 1.0 m/s, p = .01, respectively), whereas those who were born at term and SGA exhibited values similar to the controls (114 ± 15 mm Hg and 6.8 ± .9 m/s). Conclusion Preterm birth, rather than being SGA at term, increases BP and arterial stiffness in adolescents. © 2011 Society for Adolescent Health and Medicine.


PubMed | AP HM, University of Bonn, Hospital for Sick Children, St Judes Research Hospital and 13 more.
Type: Journal Article | Journal: Acta neuropathologica | Year: 2016

Historical risk stratification criteria for medulloblastoma rely primarily on clinicopathological variables pertaining to age, presence of metastases, extent of resection, histological subtypes and in some instances individual genetic aberrations such as MYC and MYCN amplification. In 2010, an international panel of experts established consensus defining four main subgroups of medulloblastoma (WNT, SHH, Group 3 and Group 4) delineated by transcriptional profiling. This has led to the current generation of biomarker-driven clinical trials assigning WNT tumors to a favorable prognosis group in addition to clinicopathological criteria including MYC and MYCN gene amplifications. However, outcome prediction of non-WNT subgroups is a challenge due to inconsistent survival reports. In 2015, a consensus conference was convened in Heidelberg with the objective to further refine the risk stratification in the context of subgroups and agree on a definition of risk groups of non-infant, childhood medulloblastoma (ages 3-17). Published and unpublished data over the past 5years were reviewed, and a consensus was reached regarding the level of evidence for currently available biomarkers. The following risk groups were defined based on current survival rates: low risk (>90% survival), average (standard) risk (75-90% survival), high risk (50-75% survival) and very high risk (<50% survival) disease. The WNT subgroup and non-metastatic Group 4 tumors with whole chromosome 11 loss or whole chromosome 17 gain were recognized as low-risk tumors that may qualify for reduced therapy. High-risk strata were defined as patients with metastatic SHH or Group 4 tumors, or MYCN-amplified SHH medulloblastomas. Very high-risk patients are Group 3 with metastases or SHH with TP53 mutation. In addition, a number of consensus points were reached that should be standardized across future clinical trials. Although we anticipate new data will emerge from currently ongoing and recently completed clinical trials, this consensus can serve as an outline for prioritization of certain molecular subsets of tumors to define and validate risk groups as a basis for future clinical trials.


PubMed | University of Amsterdam, AP HM, Floating Hospital for Children at Tufts Medical Center, Masaryk University and 9 more.
Type: Review | Journal: Oncotarget | Year: 2016

Research has exposed cancer to be a heterogeneous disease with a high degree of inter-tumoral and intra-tumoral variability. Individual tumors have unique profiles, and these molecular signatures make the use of traditional histology-based treatments problematic. The conventional diagnostic categories, while necessary for care, thwart the use of molecular information for treatment as molecular characteristics cross tissue types.This is compounded by the struggle to keep abreast the scientific advances made in all fields of science, and by the enormous challenge to organize, cross-reference, and apply molecular data for patient benefit. In order to supplement the site-specific, histology-driven diagnosis with genomic, proteomic and metabolomics information, a paradigm shift in diagnosis and treatment of patients is required.While most physicians are open and keen to use the emerging data for therapy, even those versed in molecular therapeutics are overwhelmed with the amount of available data. It is not surprising that even though The Human Genome Project was completed thirteen years ago, our patients have not benefited from the information. Physicians cannot, and should not be asked to process the gigabytes of genomic and proteomic information on their own in order to provide patients with safe therapies. The following consensus summary identifies the needed for practice changes, proposes potential solutions to the present crisis of informational overload, suggests ways of providing physicians with the tools necessary for interpreting patient specific molecular profiles, and facilitates the implementation of quantitative precision medicine. It also provides two case studies where this approach has been used.


Fabre A.,Aix - Marseille University | Charroux B.,Aix - Marseille University | Martinez-Vinson C.,AP HP | Roquelaure B.,AP HM | And 14 more authors.
American Journal of Human Genetics | Year: 2012

Syndromic diarrhea (or trichohepatoenteric syndrome) is a rare congenital bowel disorder characterized by intractable diarrhea and woolly hair, and it has recently been associated with mutations in TTC37. Although databases report TTC37 as being the human ortholog of Ski3p, one of the yeast Ski-complex cofactors, this lead was not investigated in initial studies. The Ski complex is a multiprotein complex required for exosome-mediated RNA surveillance, including the regulation of normal mRNA and the decay of nonfunctional mRNA. Considering the fact that TTC37 is homologous to Ski3p, we explored a gene encoding another Ski-complex cofactor, SKIV2L, in six individuals presenting with typical syndromic diarrhea without variation in TTC37. We identified mutations in all six individuals. Our results show that mutations in genes encoding cofactors of the human Ski complex cause syndromic diarrhea, establishing a link between defects of the human exosome complex and a Mendelian disease. © 2012 The American Society of Human Genetics.


Bingenheimer K.,AP HM | Temprado J.J.,Aix - Marseille University | Harnagea M.,Aix - Marseille University | Bricot N.,Aix - Marseille University | And 2 more authors.
Neuroscience Letters | Year: 2015

We investigated the effects of lightly touching fixed and mobile supports on gait parameters and center of mass oscillations in visually restricted young adults. Fourteen healthy male and female adults of mean. = 23.6 years (SD. = 1.6 years). Twelve walking conditions were completed on the GAITRite measurement system, resulting from crossing 3 conditions of visual restriction (no restriction, partial restriction, blindfolded) and 4 conditions of haptic supplementation (no supplementation, with a cane used as "light touch", with a cane sliding on the ground, while touching a soft elastic handrail). Gait speed, stance time, step length and the basis of support were measured. Accelerations of center of mass were also recorded through an accelerometer and the displacements of center of mass were analyzed. Results showed that visual restriction decreased in gait speed, reduced step length, while it increased the base of support and the amplitude of CoM displacements. In the full restriction condition, haptic supplementation provided by the use of the classic cane improved normalized stance time (%). In addition, in the no vision condition, both the classic cane and the soft handrail increased step length and reduced medio-lateral oscillations of the CoM. These results suggest that in visually restricted healthy adults, lightly touching a fixed (soft handrail) or a mobile (classic cane) support contributes to adaptation of gait parameters and postural control during locomotion. © 2015.

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