301 research outputs found

    Modelo impresso em 3D usado num planeamento cirúrgico de um cão com radius curvus

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    An 8 month-old, 10 kg male Azawakh dog was presented due to worsening forelimb gait and exercise intolerance. The right forelimb presented gross angular limb deformity with carpal valgus and radial procurvatum. Surgical planning based on radiographs allowed calculation of the centers of rotation and angularity (CORAs). The computer tomography data were used to generate 3D reconstructions of the antebrachium to aid the detection of the orthopaedic problems. With proper imaging software, the nature of the deformity and its degree were quantified using a previously unreported method based on the CORAs as a 3D printed model of anatomical area of interest. This 3D printed model was used by the surgeon to simulate the surgery with all orthopaedic steps, which included a partial ulna osteotomy and a double cuneiform osteotomy of the radius performed at the level of CORAs and stabilized with bone plates and screws. After 7 weeks, radiographs revealed bone union. At 8 months after surgery the animal presented a complete recovery of the involved forelimb. CORAs method combined with computed tomography and 3D model was useful to plan and simulate surgical procedures, including the corrective surgery of forelimb deformities in a dog which improved the surgical efficiency comparatively to the conventional pre-operative study.Um cão com 8 meses de idade, 10kg de peso vivo, macho da raça Azawakh foi apresentado à clínica devido à intolerância ao exercício e agravamento da marcha do membro anterior. O membro anterior direito apresentou uma deformidade angular com valgus carpal e com um procarvatum radial. O planeamento cirúrgico inicialmente baseado em exames radiográficos possibilitou o cálculo dos centros de rotação e angulação articulares (CORAs). O exame de tomografia computadorizada foi utilizado juntamente com um software de imagiologia para obter o modelo 3D virtual da área anatómica de interesse que foi posteriormente impresso em 3D e que permitiu quantificar micrometricamente a deformação óssea presente. Este modelo 3D foi utilizado pelos cirurgiões para executar uma simulação cirúrgica completa que englobou todos os procedimentos cirúrgicos, que incluiu a realização de várias osteotomias e aplicação do material cirúrgico (placas e parafusos). Com base na simulação cirúrgica foi executada a cirurgia ao animal. Decorridas sete semanas, as radiografias demonstraram uma correta regeneração óssea. Oito meses após a cirurgia o animal apresentou uma recuperação completa. O método dos CORAs juntamente com a tomografia computadorizada e com a utilização do modelo 3D revelou-se útil no planeamento e na simulação dos vários procedimentos cirúrgicos, resultando numa melhoria significativa da eficiência cirúrgica

    Identification of Class I HLA T Cell Control Epitopes for West Nile Virus

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    The recent West Nile virus (WNV) outbreak in the United States underscores the importance of understanding human immune responses to this pathogen. Via the presentation of viral peptide ligands at the cell surface, class I HLA mediate the T cell recognition and killing of WNV infected cells. At this time, there are two key unknowns in regards to understanding protective T cell immunity: 1) the number of viral ligands presented by the HLA of infected cells, and 2) the distribution of T cell responses to these available HLA/viral complexes. Here, comparative mass spectroscopy was applied to determine the number of WNV peptides presented by the HLA-A*11:01 of infected cells after which T cell responses to these HLA/WNV complexes were assessed. Six viral peptides derived from capsid, NS3, NS4b, and NS5 were presented. When T cells from infected individuals were tested for reactivity to these six viral ligands, polyfunctional T cells were focused on the GTL9 WNV capsid peptide, ligands from NS3, NS4b, and NS5 were less immunogenic, and two ligands were largely inert, demonstrating that class I HLA reduce the WNV polyprotein to a handful of immune targets and that polyfunctional T cells recognize infections by zeroing in on particular HLA/WNV epitopes. Such dominant HLA/peptide epitopes are poised to drive the development of WNV vaccines that elicit protective T cells as well as providing key antigens for immunoassays that establish correlates of viral immunity. © 2013 Kaabinejadian et al

    Vandetanib for the Treatment of Advanced Medullary Thyroid Cancer Outside a Clinical Trial: Results from a French Cohort

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    BACKGROUND: A randomized phase III trial demonstrated that vandetanib treatment is effective in patients with metastatic medullary thyroid cancer (MTC), leading to regulatory approval, but its use may be associated with toxicities that require specific monitoring and management. The objective of the present study performed in France was to describe the toxicity profile and efficacy of vandetanib treatment when given outside any trial. METHODS: Sixty-eight patients were treated with vandetanib in the frame of a temporary use authorization (ATU) in France from August 2010 to February 2012, when the drug was available on request for patients with locally advanced or metastatic MTC. Patients were registered by the French health authorities, and characteristics, treatment parameters, toxicity profile, and efficacy were retrospectively reviewed. Eight patients were excluded from the analysis because vandetanib treatment was not administered (n=3), had been given in a trial before ATU (n=3), or was given for a non-MTC cancer (n=2). RESULTS: Data from the 60 MTC patients were analyzed. Mean age was 58 years (range 11-83 years), 39 patients were male, and six had hereditary MTC. Fifty-six (93%) had metastatic disease in the mediastinum (82%), bones (65%), liver (53%), or lung (53%), and four had only locally advanced disease. At the time of study evaluation, with a median follow-up of 20 months and a median duration of treatment of 9.7 months (range 0.3-36 months), 15 patients were continuing vandetanib treatment (range 18-36 months). Median progression-free survival was 16.1 months. Twenty-five patients discontinued treatment for disease progression (range 0.3-29 months). Best tumor response was a complete response in one patient, a partial response in 12 (20%), stable disease in 33 (55%), and progression in seven patients (12%). All patients had at least one adverse event (AE) during treatment. The main AEs were skin toxicity, diarrhea, and asthenia. Sixteen patients (27%) discontinued treatment for toxicity, and one patient died from vandetanib-induced cardiac toxicity. CONCLUSIONS: Vandetanib is an effective option for patients with advanced MTC. AEs should be monitored carefully and should be minimized by educating both patients and care providers and by applying symptomatic treatment and dose reduction

    Antagonistic Regulation of Apoptosis and Differentiation by the Cut Transcription Factor Represents a Tumor-Suppressing Mechanism in Drosophila

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    Apoptosis is essential to prevent oncogenic transformation by triggering self-destruction of harmful cells, including those unable to differentiate. However, the mechanisms linking impaired cell differentiation and apoptosis during development and disease are not well understood. Here we report that the Drosophila transcription factor Cut coordinately controls differentiation and repression of apoptosis via direct regulation of the pro-apoptotic gene reaper. We also demonstrate that this regulatory circuit acts in diverse cell lineages to remove uncommitted precursor cells in status nascendi and thereby interferes with their potential to develop into cancer cells. Consistent with the role of Cut homologues in controlling cell death in vertebrates, we find repression of apoptosis regulators by Cux1 in human cancer cells. Finally, we present evidence that suggests that other lineage-restricted specification factors employ a similar mechanism to put the brakes on the oncogenic process
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