Influence of oral beclomethasone dipropionate on early non-infectious pulmonary outcomes after allogeneic hematopoietic cell transplantation: results from two randomized trials.

Early non-infectious pulmonary complications represent a significant cause of mortality after hematopoietic cell transplantation (HCT). We tested the hypothesis that oral beclomethasone dipropionate (BDP) is effective for preventing early non-infectious pulmonary complications after allogeneic HCT. We retrospectively reviewed the medical records of 120 patients, 60 in each treatment arm, to identify non-infectious and infectious pulmonary events and pulmonary function test results from all patients who participated in two randomized trials of oral BDP for treatment of acute gastrointestinal GVHD. 17-Beclomethasone monopropionate (17-BMP), the active metabolite of BDP, was evaluated in blood from the right atrium in four patients. Thirty-three of 42 (79%) placebo-treated patients experienced a decrease of the DL(CO) from pretransplant to day 80 after transplant, compared with 27 of 49 (55%) BDP-treated patients (P=0.02). In the first 200 days after randomization, there were no cases of non-infectious pulmonary complications in BDP-treated patients, vs four cases among placebo-treated patients (P=0.04). Levels of 17-BMP were detected in atrial blood at steady state. Delivery of a potent glucocorticoid such as 17-BMP to the pulmonary artery after oral dosing of BDP may be useful in modulating pulmonary inflammation and preventing the development of non-infectious pulmonary complications after allogeneic HCT.Bone Marrow Transplantation advance online publication, 29 June 2009; doi:10.1038/bmt.2009.129

Perfil pragmático longitudinal de uma criança no espectro da neuropatia auditiva Longitudinal pragmatic profile of a child with auditory neuropathy spectrum disorder

A maior parte da comunicação humana depende da conversão de ideias em linguagem, envolvendo a interação de todos os seus componentes - fonológico, semântico, sintático e pragmático. A pragmática estuda a relação entre o significado social da linguagem e seu conteúdo semântico, manifestado pelo ato comunicativo em si. O espectro da neuropatia auditiva gera uma dessincronia na condução nervosa, contribuindo para o prejuízo na percepção da fala. Na criança deficiente auditiva, o processo de aquisição e desenvolvimento da linguagem pode ser estimulado com a intervenção. O objetivo dessa pesquisa foi realizar acompanhamento longitudinal do uso das habilidades pragmáticas de comunicação por uma criança com espectro da neuropatia auditiva. A criança realizou intervenção fonoaudiológica por três anos na área de Audiologia Educacional. Foram gravadas conversações espontâneas, ao início de cada ano, transcritas e analisadas segundo protocolo de habilidades comunicativas verbais. Na gravação inicial, a criança apresentou maior número de habilidade de respostas diretas; porém, estas foram ampliadas com o fornecimento de respostas mais complexas ao longo da intervenção. Na última gravação, já propõe novos tópicos de discurso, realiza narrativas e argumentações. O surgimento de habilidades comunicativas refinadas é explicado pelo desenvolvimento da linguagem, que é potencializado pela terapia com deficientes auditivos. Pode-se concluir que para o caso apresentado a intervenção fonoaudiológica proporcionou melhora nas habilidades pragmáticas de comunicação.<br>Human communication depends mostly on the conversion of ideas into language, involving the interaction among all its components - phonological, semantic, syntactic and pragmatic. Pragmatics studies the relationship between the social meaning of language and its semantic content, expressed by the communicative act itself. Auditory neuropathy spectrum disorder generates a dyssynchrony in nerve conduction, contributing to an impairment in speech perception. In hearing impaired children the language acquisition and development process can be stimulated with intervention. The aim of this study was to present a longitudinal follow-up of the use of pragmatic communication abilities by a child with auditory neuropathy spectrum disorder. The child received speech-language pathology therapy during three years in the Educational Audiology area. Video recordings of spontaneous conversation were made in the beginning of each year. These recordings were transcribed and analyzed according to the verbal communicative abilities protocol. In the initial recording, the most frequent ability presented by the child was the direct response; however these were extended to more complex responses during the intervention. In the last recording the child proposes new topics of discourse, produce narratives and arguments. The emergence of more sophisticated communication skills is justified by the language development, which benefits from language therapy with hearing impaired children. This suggests that, for the case study described, speech-language pathology therapy contributed to the improvement of pragmatic communication abilities

Third complementarity-determining region of mutated V(H) immunoglobulin genes contains shorter V, D, J, P, and N components than non-mutated genes

The third complementarity-determining region (CDR3) of immunoglobulin variable genes for the heavy chain (V(H)) has been shown to be shorter in length in hypermutated antibodies than in non-hypermutated antibodies. To determine which components of CDR3 contribute to the shorter length, and if there is an effect of age on the length, we analysed 235 cDNA clones from human peripheral blood of V(H)6 genes rearranged to immunoglobulin M (IgM) constant genes. There was similar use of diversity (D) and joining (J(H)) gene segments between clones from young and old donors, and there was similar use of D segments among the mutated and non-mutated heavy chains. However, in the mutated heavy chains, there was increased use of shorter J(H)4 segments and decreased use of longer J(H)6 segments compared to the non-mutated proteins. The overall length of CDR3 did not change with age within the mutated and non-mutated categories, but was significantly shorter by three amino acids in the mutated clones compared to the non-mutated clones. Analyses of the individual components that comprise CDR3 indicated that they were all shorter in the mutated clones. Thus, there were more nucleotides deleted from the ends of V(H), D, and J(H) gene segments, and fewer P and N nucleotides added. The results suggest that B cells bearing immunoglobulin receptors with shorter CDR3s have been selected for binding to antigen. A smaller CDR3 may allow room in the antibody binding pocket for antigen to interact with CDRs 1 and 2 as well, so that as the VDJ gene undergoes hypermutation, substitutions in all three CDRs can further contribute to the binding energy

Using Narratives and Portraits to Foster Reflexivity and Learning from Experience in Healthcare Organizations in Italy and Norway

This chapter positions the narrative approach as consolidated practice in the field of organizational studies, and explores and expands its potential to detect the interpretations that practitioners make of the realities in which they live, thus to grasp their cultural, social, personal, practical features. The use of ad hoc narratives as an art-based method is discussed as a way to foster reflexivity and learning from experience. Narratives are presented with illustrative examples from two different healthcare fields as a means for detecting material and symbolic dimensions, the weaving of roles, objects, critical incidents, shifting points, routine in use, which can be elaborated on, developing negotiation and relational processes. The distinctive feature of this approach is the relational texture that develops around a narrative and reflexive space, which is a basic condition in our proposal of art-based intervention

Keratinocyte growth factor ameliorates acute graft-versus-host disease in a novel nonmyeloablative haploidentical transplantation model

Allogeneic stem cell transplantations (SCT) are currently being used as a therapy for hematological malignancies, some solid tumors and nonmalignant bone marrow deficiencies. Nevertheless, clinical applicability is limited due to toxicity of conditioning regimens, graft-versus-host disease (GVHD) and the scarcity of HLA-identical family donors. New concepts are based on nonmyeloablative conditioning to reduce toxicity, prevention or amelioration of GVHD and the use of haploidentical donors to increase donor availability. To combine these requirements, we have developed a nonmyeloablative conditioning regimen, consisting of low-dose total body irradiation and cyclophosphamide-based chemotherapy. In a haploidentical F1 --> F1 mouse model, this nonmyeloablative transplantation protocol resulted in stable full donor chimerism, but also in the development of severe GVHD. Administration of keratinocyte growth factor (KGF) reduced GVHD, evident as reduced weight loss and a lesser degree of dermatitis, compared to saline-treated controls. KGF preserved plasma citrulline and tumor necrosis factor-alpha levels, both indicative for reduced injury to the gastrointestinal tract. This was confirmed by histological findings. At 6 months after transplantation, survival rates were significantly higher in KGF-treated animals as compared to phosphate buffered saline-treated controls. These results indicate that KGF preserves gut integrity and might therefore contribute substantially to reduction of lethal GVHD in (nonmyeloablative) haploidentical transplantation