120 research outputs found
Les lésions médullaires traumatiques : épidémiologie et perspectives
AbstractObjectiveSpecify the epidemiological data on the acute spinal cord injuries and define a group of patients that could benefit from cellular transplantation therapy designed with the aim of repair and regeneration of damaged spinal cord tissues.Material and methodsFive years monocentric (Gui-de-Chauliac Hospital, Montpellier, France) retrospective analysis of patients suffering from spinal cord injury (SCI). Spinal cord injured-patients, defined as sensory-motor complete, underwent a clinical evaluation following American Spinal Injury Association (ASIA) and functional type 2 Spinal Cord Independence Measure (SCIM2) scorings as well as radiological evaluation through spinal cord magnetic resonance imaging (MRI).ResultsOne hundred and fifty-seven medical records were reviewed and we selected and re-examined 20 patients with complete thoracic spinal cord lesion. Clinical and radiological evaluations of these patients demonstrated, in 75 % of the cases, an absence of clinical progression after a mean of 49months. Radiological abnormalities were constantly present in the initial (at the admission to hospital) and control (re-evaluation) MRI and no reliable predictive criteria of prognosis had been found.Discussion/ConclusionWe compare our results to the literature and discuss advantages and limits of cellular transplantation strategies for these patients.RĂ©sumĂ©ObjectifsConnaĂźtre les donnĂ©es Ă©pidĂ©miologiques de notre rĂ©gion sanitaire sur les traumatismes mĂ©dullaires. Au sein de cette population, sĂ©lectionner les patients susceptibles de bĂ©nĂ©ficier de thĂ©rapie cellulaire dans la moelle Ă©piniĂšre lĂ©sĂ©e dans lâobjectif de rĂ©gĂ©nĂ©rer le tissu nerveux. Ăvaluer Ă distance ces patients.Patients et mĂ©thodeAnalyse rĂ©trospective de tous les patients pris en charge pour un traumatisme vertĂ©bro-mĂ©dullaire. RĂ©Ă©valuation clinique et radiologique des patients prĂ©sentant une atteinte mĂ©dullaire thoracique sensitivomotrice complĂšte. RĂ©Ă©valuation rĂ©alisĂ©e par le score de lâAmerican Spinal Injury Association (ASIA), le score fonctionnel Type 2 Spinal Cord Independence Measure (SCIM2) et contrĂŽle radiologique par une IRM mĂ©dullaire.RĂ©sultatsCent cinquante-sept dossiers de patients ont Ă©tĂ© analysĂ©s et 28 patients prĂ©sentaient une lĂ©sion mĂ©dullaire complĂšte. Une Ă©valuation clinique et radiologique rĂ©alisĂ©e chez 20 patients sur 28 (71 %) a montrĂ© lâabsence dâĂ©volution clinique dans 75 % des cas dans un dĂ©lai moyen de 49 mois. Les anomalies radiologiques Ă©taient prĂ©sentes dans 100 % des cas sur lâIRM initiale et de contrĂŽle sans quâaucun critĂšre fiable prĂ©dictif de bon pronostic nâest retrouvĂ©.Discussion/conclusionNous prĂ©sentons ces rĂ©sultats comparativement Ă ceux de la littĂ©rature et nous discutons chez ces malades les stratĂ©gies de transplantation cellulaire, leurs limites actuelles et les progrĂšs nĂ©cessaires pour obtenir des rĂ©sultats
Anatomical study of serotonergic innervation and 5-HT1A receptor in the human spinal cord
Serotonergic innervation of the spinal cord in mammals has multiple roles in the control of motor, sensory and visceral functions. In rats, functional consequences of spinal cord injury at thoracic level can be improved by a substitutive transplantation of serotonin (5-HT) neurons or regeneration under the trophic influence of grafted stem cells. Translation to either pharmacological and/or cellular therapies in humans requires the mapping of the spinal cord 5-HT innervation and its receptors to determine their involvement in specific functions. Here, we have performed a preliminary mapping of serotonergic processes and serotonin-lA (5-HT1A) receptors in thoracic and lumbar segments of the human spinal cord. As in rodents and non-human primates, 5-HT profiles in human spinal cord are present in the ventral horn, surrounding motoneurons, and also contact their presumptive dendrites at lumbar level. 5-HT1A receptors are present in the same area, but are more densely expressed at lumbar level. 5-HT profiles are also present in the intermediolateral region, where 5-HT1A receptors are absent. Finally, we observed numerous serotonergic profiles in the superficial part (equivalent of Rexed lamina II) of the dorsal horn, which also displayed high levels of 5-HT1A receptors. These findings pave the way for local specific therapies involving cellular and/or pharmacological tools targeting the serotonergic system
Grafted Human Embryonic Progenitors Expressing Neurogenin-2 Stimulate Axonal Sprouting and Improve Motor Recovery after Severe Spinal Cord Injury
7 p.Background: Spinal cord injury (SCI) is a widely spread pathology with currently no effective treatment for any symptom. Regenerative medicine through cell transplantation is a very attractive strategy and may be used in different non-exclusive ways to promote functional recovery. We investigated functional and structural outcomes after grafting human embryonic neural progenitors (hENPs) in spinal cord-lesioned rats.Methods and Principal Findings: With the objective of translation to clinics we have chosen a paradigm of delayed grafting, i.e., one week after lesion, in a severe model of spinal cord compression in adult rats. hENPs were either naive or engineered to express Neurogenin 2 (Ngn2). Moreover, we have compared integrating and non-integrating lentiviral vectors, since the latter present reduced risks of insertional mutagenesis. We show that transplantation of hENPs transduced to express Ngn2 fully restore weight support and improve functional motor recovery after severe spinal cord compression at thoracic level. This was correlated with partial restoration of serotonin innervations at lumbar level, and translocation of 5HT1A receptors to the plasma membrane of motoneurons. Since hENPs were not detectable 4 weeks after grafting, transitory expression of Ngn2 appears sufficient to achieve motor recovery and to permit axonal regeneration. Importantly, we also demonstrate that transplantation of naive hENPs is detrimental to functional recovery.Conclusions and Significance: Transplantation and short-term survival of Ngn2-expressing hENPs restore weight support after SCI and partially restore serotonin fibers density and 5HT1A receptor pattern caudal to the lesion. Moreover, grafting of naive-hENPs was found to worsen the outcome versus injured only animals, thus pointing to the possible detrimental effect of stem cell-based therapy per se in SCI. This is of major importance given the increasing number of clinical trials involving cell grafting developed for SCI patients.This study was supported by the European Union FP6 "RESCUE" STREP; the "Institut pour la Recherche sur la Moelle Epiniere"; the "Academie de Medecine"; the "Societe Francaise de Neurochirurgie"; "Verticale" and the "Association Demain Debout Aquitaine". The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
Chronic Hepatitis C Treatment in Patients with Drug Injection History: Findings of the INTEGRATE Prospective, Observational Study.
INTRODUCTION: People who inject drugs represent an under-treated chronic hepatitis C virus (HCV)-infected patient population. METHODS: INTEGRATE was a prospective, observational study investigating the effectiveness, safety, and adherence in routine clinical practice to telaprevir in combination with peg-interferon and ribavirin (Peg-IFN/RBV) in patients with history of injecting drug use chronically infected with genotype 1 HCV. RESULTS: A total of 46 patients were enrolled and included in the intent-to-treat (ITT) population. Among heroin and/or cocaine users (n = 37; 80%), 22% reported use in the past month; 74% (34/46) of patients were on opioid substitution therapy in the pre-treatment phase, and 43% (20/46) discontinued HCV treatment prematurely. Sustained virologic response rate was 54% (25/46) in the ITT population and 74% (25/34) in the per protocol (evaluable-for-effectiveness) population. The main reason for failure in the ITT analysis was loss to follow-up (n = 8; 17%). Adverse events occurred in 91% (42/46) of patients. Mean patient-reported adherence to study drugs was >89% at Week 4, Week 12 and end of treatment. CONCLUSION: Despite a high rate of treatment discontinuation (including loss to follow-up), self-reported adherence to treatment was good and virologic cure rates were similar to those reported in large real-world cohorts. Our findings suggest that people with a history of injecting drug use should be considered for treatment of chronic HCV infection, and highlight the need for improvements in patient support to boost retention in care and, in turn, help to prevent reinfection and transmission. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov identifier, NCT01980290. FUNDING: Janssen Pharmaceuticals
Safety and on-treatment efficacy of telaprevir: the early access programme for patients with advanced hepatitis C
Background and aim Severe adverse events (AEs) compromise the outcome of direct antiviral agent-based treatment in patients with advanced liver fibrosis due to HCV infection. HEP3002 is an ongoing multinational programme to evaluate safety and efficacy of telaprevir (TVR) plus pegylated-interferon-alpha (PEG-IFN alpha) and ribavirin (RBV) in patients with advanced liver fibrosis caused by HCV genotype 1 (HCV-1).Methods 1782 patients with HCV-1 and bridging fibrosis or compensated cirrhosis were prospectively recruited from 16 countries worldwide, and treated with 12 weeks of TVR plus PEG-IFN/RBV, followed by 12 or 36 weeks of PEG-IFN and RBV (PR) alone dependent on virological response to treatment and previous response type.Results 1587 patients completed 12 weeks of triple therapy and 4 weeks of PR tail (53% cirrhosis, 22% HCV-1a). By week 12, HCV RNA was undetectable in 85% of naives, 88% of relapsers, 80% of partial responders and 72% of null responders. Overall, 931 patients (59%) developed grade 1-4 anaemia (grade 3/4 in 31%), 630 (40%) dose reduced RBV, 332 (21%) received erythropoietin and 157 (10%) were transfused. Age and female gender were the strongest predictors of anaemia. 64 patients (4%) developed a grade 3/4 rash. Discontinuation of TVR due to AEs was necessary in 193 patients (12%). Seven patients died (0.4%, six had cirrhosis).Conclusions in compensated patients with advanced fibrosis due to HCV-1, triple therapy with TVR led to satisfactory rates of safety, tolerability and on-treatment virological response with adequate managements of AEs.Janssen PharmaceuticsUniv Milan, Div Gastroenterol, Dept Med, Fdn IRCCS Ca Granda Osped Maggiore Policlin, Milan, ItalyHosp Univ 12 Octubre, Secc Aparato Digest, Madrid, SpainIM Sechenov First Moscow State Med Univ, EM Tareev Clin Nephrol Internal & Occupat Med, Moscow, RussiaUniversidade Federal de SĂŁo Paulo, Viral Hepatitis Div Infect Dis, Outpatient Clin HIV, SĂŁo Paulo, BrazilUniv Sydney, Royal Prince Alfred Hosp, AW Morrow Gastroenterol & Liver Ctr, Sydney, NSW 2006, AustraliaCharles Univ Prague, Fac Med 1, Dept Internal Med, Prague, Czech RepublicCent Mil Hosp Prague, Prague, Czech RepublicUniv Libre Brussels, Dept Gastroenterol Hepatopancreatol & Digest Onco, Erasme Univ Hosp, Liver Unit, Brussels, BelgiumCarol Davila Univ Med & Pharm, Natl Inst Infect Dis, Bucharest, RomaniaJanssen Pharmaceut, B-2340 Beerse, BelgiumJanssen Pharmaceut, Paris, FranceJanssen Res & Dev, Titusville, NJ USAJanssen Res & Dev, High Wycombe, Bucks, EnglandJanssen Cilag AG, Zug, SwitzerlandHannover Med Sch, D-30623 Hannover, GermanyUniversidade Federal de SĂŁo Paulo, Viral Hepatitis Div Infect Dis, Outpatient Clin HIV, SĂŁo Paulo, BrazilWeb of Scienc
Conductive Cellulose Composites with Low Percolation Threshold for 3D Printed Electronics
We are reporting a 3D printable composite paste having strong thixotropic rheology. The composite has been designed and investigated with highly conductive silver nanowires. The optimized electrical percolation threshold from both simulation and experiment is shown from 0.7 vol. % of silver nanowires which is significantly lower than other composites using conductive nano-materials. Reliable conductivity of 1.19 Ă 102 S/cm has been achieved from the demonstrated 3D printable composite with 1.9 vol. % loading of silver nanowires. Utilizing the high conductivity of the printable composites, 3D printing of designed battery electrode pastes is demonstrated. Rheology study shows superior printability of the electrode pastes aided by the cellulose\u27s strong thixotropic rheology. The designed anode, electrolyte, and cathode pastes are sequentially printed to form a three-layered lithium battery for the demonstration of a charging profile. This study opens opportunities of 3D printable conductive materials to create printed electronics with the next generation additive manufacturing process
Primary spinal cord tumors of childhood: effects of clinical presentation, radiographic features, and pathology on survival
To determine the relationship between clinical presentation, radiographic features, pathology, and treatment on overall survival of newly diagnosed pediatric primary spinal cord tumors (PSCT). Retrospective analysis of all previously healthy children with newly diagnosed PSCT at a single institution from 1995 to present was performed. Twenty-five pediatric patients (15 boys, average 7.9Â years) were diagnosed with PSCT. Presenting symptoms ranged from 0.25 to 60Â months (average 7.8Â months). Symptom duration was significantly shorter for high grade tumors (average 1.65Â months) than low grade tumors (average 11.2Â months) (PÂ =Â 0.05). MRI revealed tumor (8 cervical, 17 thoracic, 7 lumbar, 7 sacral) volumes of 98â94,080Â mm3 (average 19,474Â mm3). Homogeneous gadolinium enhancement on MRI correlated with lower grade pathology (PÂ =Â 0.003). There was no correlation between tumor grade and volume (PÂ =Â 0.63) or edema (PÂ =Â 0.36) by MRI analysis. Median survival was 53Â months and was dependent on tumor grade (PÂ =Â 0.05) and gross total resection (PÂ =Â 0.01) but not on gender (PÂ =Â 0.49), age of presentation (PÂ =Â 0.82), duration of presenting symptoms (PÂ =Â 0.33), or adjuvant therapies (PÂ =Â 0.17). Stratified KaplanâMeier analysis confirmed the association between degree of resection and survival after controlling for tumor grade (PÂ =Â 0.01). MRI homogeneous gadolinium enhancement patterns may be helpful in distinguishing low grade from high grade spinal cord malignancies. While tumor grade and gross total resection rather than duration of symptoms correlated with survival in our series, greater than one-third of patients had reported symptoms greater than 6Â months duration prior to diagnosis
Surface Acoustic Wave Device with Reduced Insertion Loss by Electrospinning P(VDFâTrFE)/ZnO Nanocomposites
Spatio-Temporal Progression of Grey and White Matter Damage Following Contusion Injury in Rat Spinal Cord
Cellular mechanisms of secondary damage progression following spinal cord injury remain unclear. We have studied the extent of tissue damage from 15 min to 10 weeks after injury using morphological and biochemical estimates of lesion volume and surviving grey and white matter. This has been achieved by semi-quantitative immunocytochemical methods for a range of cellular markers, quantitative counts of white matter axonal profiles in semi-thin sections and semi-quantitative Western blot analysis, together with behavioural tests (BBB scores, ledged beam, random rung horizontal ladder and DigiGaitâą analysis). We have developed a new computer-controlled electronic impactor based on a linear motor that allows specification of the precise nature, extent and timing of the impact. Initial (15 min) lesion volumes showed very low variance (1.92±0.23 mm3, mean±SD, nâ=â5). Although substantial tissue clearance continued for weeks after injury, loss of grey matter was rapid and complete by 24 hours, whereas loss of white matter extended up to one week. No change was found between one and 10 weeks after injury for almost all morphological and biochemical estimates of lesion size or behavioural methods. These results suggest that previously reported apparent ongoing injury progression is likely to be due, to a large extent, to clearance of tissue damaged by the primary impact rather than continuing cell death. The low variance of the impactor and the comprehensive assessment methods described in this paper provide an improved basis on which the effects of potential treatment regimes for spinal cord injury can be assessed
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