Absence of BK viremia clearance after low-dose cidofovir therapy in kidney transplant recipients with BK virus associated nephropathy

Background: BK virus associated nephropathy occurs in 1-10% of kidney transplant recipients and may be a cause of graft loss. This infection is difficult to manage because of the absence of specific therapy. Cidofovir, a DNA polymerase inhibitor approved for the treatment of CMV retinitis, has shown in vitro activity against BK virus and some clinical efficacy when used at low-dose in uncontrolled series. Objective: To assess the efficacy of low-dose Cidofovir in the treatment of BK virus associated nephropathy. Method: Two adult kidney transplant recipients with biopsy-proven BK nephropathy and persistent high viremia (>10,000 copies/ml) despite 3-month reduction of immunosuppressive therapy were treated by Cidofovir 0.5 mg/kg fortnightly for a total of 16 weeks (8 doses). Clinical response was assessed by following BK viremia. Results: No decrease in BK viremia was observed at any point during cidofovir therapy (see figure). Creatinine clearance remained stable during therapy and no side-effects of Cidofovir were observed. Conclusions: Low-dose Cidofovir therapy was not associated with a clearance or with a significant decrease of BK viremia. This pilot study does not confirm previous reports suggesting clinical efficacy of Cidofovir for BK virus associated nephropathy.

3D dose reconstruction for narrow beams using ion chamber array measurements.

3D dose reconstruction is a verification of the delivered absorbed dose. Our aim was to describe and evaluate a 3D dose reconstruction method applied to phantoms in the context of narrow beams. A solid water phantom and a phantom containing a bone-equivalent material were irradiated on a 6 MV linac. The transmitted dose was measured by using one array of a 2D ion chamber detector. The dose reconstruction was obtained by an iterative algorithm. A phantom set-up error and organ interfraction motion were simulated to test the algorithm sensitivity. In all configurations convergence was obtained within three iterations. A local reconstructed dose agreement of at least 3% / 3mm with respect to the planned dose was obtained, except in a few points of the penumbra. The reconstructed primary fluences were consistent with the planned ones, which validates the whole reconstruction process. The results validate our method in a simple geometry and for narrow beams. The method is sensitive to a set-up error of a heterogeneous phantom and interfraction heterogeneous organ motion.

História, memória e representações sociais: por uma abordagem crítica e interdisciplinar

Ao resgatar aspectos da discussão de que a história possui uma memória, pretende-se indicar alguns desafios relacionados aos estudos baseados na teoria das representações sociais e em sua historicidade. As discussões aqui propostas fundamentam-se, sobretudo, na produção de Paul Ricoeur e nas historiografias francesa e brasileira, de modo a entender memória e história como "regimes de gestão do passado". Apontando-se algumas singularidades do atual "regime de historicidade", em que há uma fratura entre "espaço de experiência" e "horizonte de expectativa", destacam-se algumas consequências acerca dos usos públicos da memória e da história, por meio de breves menções ao golpe militar brasileiro e à criação da Comissão Nacional da Verdade, que servem de provocação para a abordagem das representações sociais.

High-dose therapy and autologous hematopoietic stem cell transplant in T-cell lymphoma: a single center experience.

Abstract We report here the long-term outcome of autologous stem cell transplant in peripheral T-cell lymphoma (PTCL). Forty-three consecutive patients with PTCL diagnosed between 2000 and 2011 were treated with high-dose chemotherapy (HDCT) and autologous stem cell transplant (ASCT) in our center. Diagnoses included PTCL-not otherwise specified (n = 19), anaplastic large cell lymphoma (n = 11), angioimmunoblastic T-cell lymphoma (n = 5), enteropathy-associated T-cell lymphoma (n = 5) and other rare subtypes (n = 3). Thirty-six patients with a median age of 50 years (range 22-65) were transplanted in first response and seven after relapse. After a median follow-up of 63 months, estimated overall survival at 12 years was 40%, progression-free survival at 12 years was 34% and event-free survival at 12 years was 30%. On univariate analysis, age less than 50 years and no B symptoms at diagnosis were significantly associated with prolonged overall and progression-free-survival. HDCT/ASCT for peripheral T-cell lymphoma can lead to long-term survival for patients responding to induction chemotherapy.

Construir e mobilizar conhecimentos numa relação crítica com os saberes

A abordagem por competência - APC - firmou-se em grande parte dos sistemas educacionais. Sua ambição: renovar o ensino dando ênfase à resolução de problemas e, com isso, superar a aprendizagem pelos alunos de saberes "mortos". Assim, a APC introduz na escola uma preocupação renovada com a mobilização dos saberes. Mas o risco de cair no utilitarismo é grande: apenas os conhecimentos úteis seriam dignos de ser ensinados. No caso, ocorre um deslocamento ideológico: o pragmatismo anglo-saxão substitui o humanismo sustentado sobretudo pela filosofia das luzes. Os autores deste artigo esboçam uma via intermediária entre essas duas visões da escola.

MDCT arthrography of the hip: value of the adaptive statistical iterative reconstruction technique and potential for radiation dose reduction.

OBJECTIVE: The purpose of this article is to assess the effect of the adaptive statistical iterative reconstruction (ASIR) technique on image quality in hip MDCT arthrography and to evaluate its potential for reducing radiation dose. SUBJECTS AND METHODS: Thirty-seven patients examined with hip MDCT arthrography were prospectively randomized into three different protocols: one with a regular dose (volume CT dose index [CTDIvol], 38.4 mGy) and two with a reduced dose (CTDIvol, 24.6 or 15.4 mGy). Images were reconstructed using filtered back projection (FBP) and four increasing percentages of ASIR (30%, 50%, 70%, and 90%). Image noise and contrast-to-noise ratio (CNR) were measured. Two musculoskeletal radiologists independently evaluated several anatomic structures and image quality parameters using a 4-point scale. They also jointly assessed acetabular labrum tears and articular cartilage lesions. RESULTS: With decreasing radiation dose level, image noise statistically significantly increased (p=0.0009) and CNR statistically significantly decreased (p=0.001). We also found a statistically significant reduction in noise (p=0.0001) and increase in CNR (p≤0.003) with increasing percentage of ASIR; in addition, we noted statistically significant increases in image quality scores for the labrum and cartilage, subchondral bone, overall diagnostic quality (up to 50% ASIR), and subjective noise (p≤0.04), and statistically significant reductions for the trabecular bone and muscles (p≤0.03). Regardless of the radiation dose level, there were no statistically significant differences in the detection and characterization of labral tears (n=24; p=1) and cartilage lesions (n=40; p≥0.89) depending on the ASIR percentage. CONCLUSION: The use of up to 50% ASIR in hip MDCT arthrography helps to reduce radiation dose by approximately 35-60%, while maintaining diagnostic image quality comparable to that of a regular-dose protocol using FBP.

Revisió crítica de les bases cronològiques de la Terra Sigillata Hispanica

Un deis principals problemes que existeixen avui en dia en I'estudi de la Terra Sigillata Hispanica és la manca d'una base correcta per a suportar les datacions proposades. Malgrat les discusions que entorn de la cronologia es plantegen actualment, el verdader problcma es troba en la seva base, donat que aquesta s'ha fonamentat sobre excavacions realitzades sense les condicions metodologiques necessaries.

Efavirenz Dose Adjustment in HIV Patients with Impaired CYP2B6 Function

Efavirenz dosage adjustment in several patients with high EFV levels and presenting CNS toxicity have been successfully achieved in Switerland over the past seven years but many others have not beneficiated from dosage reduction owing to the lack of prospective studies evaluating the safety and clinical benefit of reduced dosage regimens.

Quan l'actualitat mediàtica entra a l'aula: la "mediaquest" com a eina per promoure la crítica intercultural.

Després d'analitzar alguns dels canvis que s'estan començant a generar en l'educació, per la introducció de les tecnologies de l'aprenentatge i el coneixement, i per la presència d'alumnat de procedència diversa, aquest article proposa una eina en web, la mediaquest, que ha d'ajudar el professorat perquè els alumnes esdevinguin creadors i productors de nous coneixements i no mers consumidors passius d'informacions rebudes. Es tracta, en definitiva, d'ajustar el temps analògic del professorat amb el temps digital de l'alumnat.

Bases filosòfiques per una ciència crítica de l'educació. Una entrevista a Wilfred Carr.

Wilfred Carr, professor de la Divisió d'Educació de la Universitat de Sheffield del Regne Unit, és un deis representants més destacats de la Filosofia Crítica de l'Educació. A Espanya sobretot és conegut pel Ilibre (juntament amb Stephen Kemmis) 'Teoría crítica de la enseñanza', publicat per l'editorial Martínez Roca, i per una altre de més recent, 'Hacia una ciencia crítica de la educación', publicat per l'editorial Laertes. A més, ha participat en nombrosos congressos i seminaris, entre els quals podem destacar l'aportació que va fer al Congrés Internacional de Filosofia de l'Educació reunit a Madrid el 1988 i que fou publicada per la UNED al volum d'actes.

Low-dose valganciclovir is efficacious and safe for prophylaxis of cytomegalovirus infection in kidney transplantation

Background: Optimal valganciclovir (VGC) dosage and duration for cytomegalovirus (CMV) prophylaxis in kidney transplant recipients remains controversial. This study aimed to determine GCV blood levels and efficacy/safety observed under low-dose oral VGC in kidney transplant recipients. Secondly, to quantify the variability of GCV blood levels, and its potential clinical impact. Methods: In this prospective study, each patient at risk for CMV undergoing kidney transplantation received low-dose VGC (450 mg qd) prophylaxis for 3 months, unless GFR was below 40 mL/min, in which case the dose was adapted to 450 mg every other day. GCV levels, at trough (Ctrough) and at peak (C3h) were measured monthly and CMV viremia was assessed during and after prophylaxis using real time quantitative Polymerase Chain Reaction. Adverse effects were recorded on each GCV sampling. Patients were followed up to one year after transplantation. Results: 38 kidney recipients (19 D+/R+, 11 D+/R-, 8 D-/R+) received 3-month VGC prophylaxis. Most patients (mean GFR of 59 mL/min) received 450 mg qd but the dose was reduced to 450 mg every other day in 6 patients with mean GFR of 22 mL/min. Average GCV C3h and Ctrough (regressed at 24h or 48h) were 3.9 mg/L (CV 33%, range: 1.3-8.2) and 0.4 mg/L (CV 111%, range 0.1-3.3). Population pharmacokinetic analysis showed a fair dispersion of the parameters mainly influenced by renal function. Despite this variability, patients remained aviremic during VGC prophylaxis. Neutropenia and thrombocytopenia (grade 2-4) were reported in 4% and 3% of patients respectively. During follow-up, asymptomatic CMV viremia was reported in 25% patients. One year after transplantation, 12% patients (all D+/R-) had developed a CMV disease, which was treated with a therapeutic 6-week course of oral VGC. Conclusion: Average GCV blood levels after oral administration of low-dose VGC in kidney transplant recipients were comparable to those previously reported with oral GCV prophylaxis, efficacious and well tolerated. Thus, a 3-month course of low-dose VGC is appropriate for the renal function of most kidney transplant recipients.

Low-dose radiotherapy (2x2 Gy) in indolent lymphoma

Dans la prise en charge des maladies oncologiques, la priorité est évidemment d'assurer le contrôle de la maladie (soit le taux de récidive local et la survie globale), surtout lorsque celle-ci est diagnostiquée tôt, à un stade précoce. Cependant, lorsque la maladie est plus avancée et que ce contrôle ne peut être assuré de façon raisonnable, l'accent de la prise en charge est surtout axé sur le confort du patient. Le principe est de fournir à celui-ci, dans la mesure du possible, une qualité de vie acceptable, avec notamment des douleurs bien contrôlées.Dans le cadre de ce travail de thèse, nous nous sommes intéressés à la prise en charge palliative des lymphomes non hodgkiniens (LNH) de bas grade. La survie de ces patients peut être relativement longue (de 5 à 10 ans selon les séries), cependant, le traitement est rarement à visée curative, contrairement aux lymphomes de haut grade, dont la survie est bien moindre, mais avec une chance de guérison après un traitement intensif.Plusieurs études cliniques, à la fois prospectives et rétrospectives, ont démontré l'intérêt d'une irradiation à faible dose {2x2 Gy) lors d'atteintes tymphomateuses à l'origine de symptômes gênants (douleurs, compression par une masse, dyspnée, entre autres). Etant donné la facilité d'administration de ce traitement (seulement 2 séances de radiothérapie sont nécessaires), et sa quasi absence de survenue d'effets secondaires avec cette faible dose totale (4 Gy), nous avons voulu y apporter une contribution suisse.Notre étude rétrospective a permis d'inclure 43 patients entre le CHUV et les HUG. Les résultats que nous avons obtenus sont également dans la ligne des autres études parues, avec un excellent contrôle local, soit un soulagement rapide et durable des symptômes dans la majorité des cas.Nous espérons que ce travail de thèse, publié sous forme d'un article dans « International Journal of Radiation Oncology, Biology, Physics », permettra une prise en charge plus optimale des ces patients en leur apportant un traitement facile à administrer, efficace, sans effets secondaires dans la majorité des cas, et pouvant être répété un grand nombre de fois si nécessaire.

La crítica feminista y el problema de la forma

Dice Beatriz Sarlo (2001, p. 28) que un intelectual es aquel que pone en escena los términos de un problema y obliga a una definición colectiva que los tome en cuenta. Para que esto suceda el intelectual debe ser también quien se interroga por las categorías con las que opera. Si la literatura existe como problema, según mi perspectiva, para la crítica feminista, esto se debe a que la operación que vincula el concepto de literatura y el de crítica feminista debe necesariamente definirse en relación con un horizonte hoy en retirada, pero cuya crepuscular energía obliga constantemente a apelar a sus herramientas: la estética.

Gestão do conhecimento: uma revisão crítica orientada pela abordagem da criação do conhecimento

Uma bem-sucedida sistematização da gestão do conhecimento deve considerar que o conhecimento pode existir em dois formatos, tanto na mente das pessoas, quanto em registros diversos; e a tecnologia da informação tem grande importância no acesso e na renovação dos conhecimentos. Seguindo essas preocupações, a essência da idéia de "criação do conhecimento" utilizada na área de gestão organizacional reside em pessoas poderem se encontrar e trocar experiências com outras pessoas que têm ou trabalham com certos tipos de conhecimentos, e a importância da tecnologia da informação é construir um suporte para que isso ocorra. Considerando esse ponto de vista, discutem-se, no presente artigo, esforços para trocas de conhecimentos, utilizando-se, para isso, o relacionamento entre dois formatos de conhecimentos aqueles que são inerentes às habilidades pessoais (conhecimento tácito) e aqueles que são possíveis de verbalizar e registrar (conhecimento explícito) em quatro tipos de conversões do conhecimento: socialização (tácito de um indivíduo para outro), externalização (explicitando partes do conhecimento tácito), combinação (conhecimento explícito de um indivíduo para o grupo) e internalização (captando no formato tácito o conhecimento explícito do grupo). Os argumentos aqui apresentados baseiam-se no fato de que uma efetiva criação e trabalho com o conhecimento apenas ocorre em um ambiente em que existe uma contínua conversão entre os dois formatos do conhecimento.