Success of allogeneic marrow transplantation for children with severe aplastic anaemia

Allogeneic marrow transplantation offers curative therapy for children with severe aplastic anaemia (SAA). We report the outcomes of 148 children with SAA who received human leucocyte antigen (HLA)-matched related marrow grafts between 1971 and 2010. Patients were divided into three groups, reflecting changes in conditioning and graft-versus-host disease (GVHD) prophylaxis regimens that occurred over time. Patients in Group 1 were conditioned with cyclophosphamide (CY; 200 mg/kg) followed by 'long' (102 d) methotrexate (MTX). Patients in Groups 2 and 3 received CY alone (Group 2) or combined with anti-thymocyte globulin (Group 3) followed by 'short' (days 1, 3, 6, and 11) MTX and ciclosporin (until day 180). With a median follow-up of 25 years, the 5-year survivals were 66%, 95%, and 100% for Groups 1, 2, and 3, respectively (overall P < 0·0001). The 3-year estimates of graft rejection were 22%, 32%, and 7%, respectively. The probabilities of grades III-IV acute and 2-year chronic GVHD were 15%, 0%, and 3%, and 21%, 21%, and 10%, respectively. Advances in preparative and GVHD prophylaxis regimens, and supportive care during the past 40 years have led to improved outcomes for children with SAA. These results confirm the use of allogeneic marrow transplantation for children with SAA who have HLA-matched related donors.     

Mesenchymal stromal cells protect mantle cell lymphoma cells from spontaneous and drug-induced apoptosis through secretion of B-cell activating factor and activation of the canonical and non-canonical nuclear factor κB pathways

Background

There is increasing evidence that stromal cell interactions are required for the survival and drug resistance of several types of B-cell malignancies. There is relatively little information regarding the role of the bone marrow/lymphoid microenvironment in the pathogenesis of mantle cell lymphoma. In this study we investigated the interaction of primary mantle cell lymphoma cells with stromal cells in an ex vivo co-culture system.

Design and Methods

The murine stromal cell line MS-5 and human bone marrow mesenchymal stromal cells were each co-cultured with primary mantle cell lymphoma cells for up to 7 months. Mantle cell lymphoma cultures alone or combined with human stromal cells were analyzed for cell number, cell migration, nuclear factor-κB activation and drug resistance.

Results

Co-culture of mantle cell lymphoma cells and human stromal cells results in the survival and proliferation of primary mantle cell lymphoma cells for at least 7 months compared to mantle cell lymphoma cells cultured alone. Mantle cell lymphoma-human stromal cell interactions resulted in activation of the B-cell activating factor/nuclear factor-κB signaling axis resulting in reduced apoptosis, increased mantle cell lymphoma migration and increased drug resistance.

Conclusions

Direct mantle cell lymphoma-human stromal cell interactions support long-term expansion and increase the drug-resistance of primary mantle cell lymphoma cells. This is due in part to activation of the canonical and non-canonical nuclear factor κB pathways. We also demonstrated the ability of B-cell activating factor to augment CXCL12- and CXCL13-induced cell migration. Collectively, these findings demonstrate that human stromal cell-mantle cell lymphoma interactions play a pivotal role in the pathogenesis of mantle cell lymphoma and that analysis of mantle cell lymphoma-human stromal cell interactions may help in the identification of novel targets for therapeutic use.     

IDSA clinical practice guideline for acute bacterial rhinosinusitis in children and adults

Evidence-based guidelines for the diagnosis and initial management of suspected acute bacterial rhinosinusitis in adults and children were prepared by a multidisciplinary expert panel of the Infectious Diseases Society of America comprising clinicians and investigators representing internal medicine, pediatrics, emergency medicine, otolaryngology, public health, epidemiology, and adult and pediatric infectious disease specialties. Recommendations for diagnosis, laboratory investigation, and empiric antimicrobial and adjunctive therapy were developed.     

Effect of glutamate receptor antagonists on migrating neural progenitor cells

Neurotransmitters such as glutamate are potential regulators of neurogenesis. Interference with defined glutamate receptor subtypes affects proliferation, migration and differentiation of neural progenitor cells. The cellular targets for the actions of different glutamate receptor ligands are less well known. In this study we have combined calcium imaging, measurement of membrane potential, time‐lapse imaging and immunocytochemistry to obtain a spatial overview of migrating mouse embryonic neural progenitor cell‐derived cells responding to glutamate receptor agonists and antagonists. Responses via metabotropic glutamate receptor 5 correlated with radial glial cells and dominated in the inner migration zones close to the neurosphere. Block of metabotropic glutamate receptor 5 resulted in shorter radial glial processes, a transient increase in neuron‐like cells emerging from the neurosphere and increased motility of neuron‐like cells. α‐Amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA)/kainate receptors are present on the majority of migrating neuronal cells, which with time accumulate at the outer edge of the migration zone. Blocking these receptors leads to an enhanced extension of radial glial processes and a reduced motility of neuron‐like cells. Our results indicate that functional glutamate receptors have profound effects on the motility of neural progenitor cells. The main target for metabotropic glutamate receptor 5 appears to be radial glial cells while AMPA/kainate receptors are mainly expressed in newborn neuronal cells and regulate the migratory progress of these cells. The results suggest that both metabotropic glutamate receptor 5 and AMPA/kainate receptors are of importance for the guidance of migrating embryonic progenitor cells.     

A Pilot Study of a Family-Based Treatment for Adolescent Anorexia Nervosa: 18- and 36-Month Follow-ups

The current study evaluated the outcome of family-based treatment for female adolescents with anorexia nervosa (N?=?32), at the Anorexia-Bulimia Outpatient Unit in Göteborg, Sweden. Patients/parents were assessed pre-treatment, at 18- and 36-month follow-ups concerning eating disorder symptoms, general psychopathology, family climate and BMI. At the 36-month follow-up, 75% of the patients were in full remission with reduction in eating disorder symptoms and internalizing problems and they experienced a less distant and chaotic atmosphere in their families. These results show that family-based treatment appears to be effective in adolescent anorexia nervosa patients regarding areas examined in this study.     

Psychosocial Correlates of Atrial Natriuretic Peptide: A Marker of Vascular Health

Background

Psychosocial factors have been associated with cardiovascular outcomes, but few studies have examined the association between psychosocial function and natriuretic peptides.

Purpose

The purpose of this study is to determine the predictive value of hostility, anger, and social support in relation to atrial natriuretic peptide (ANP), a marker of vascular health, among middle-aged men.

Methods

One hundred twenty-one men (mean age?=?39.8 years, SD?=?4.1) underwent assessments of ANP and completed the Cook–Medley Hostility Scale, the Spielberger State–Trait Anger Scale, and the Interview Schedule for Social Interaction.

Results

Higher levels of hostility (β?=?0.22 [95 % CI 0.04, 0.40], P?=?0.032) and trait anger (β?=?0.18 [95 % CI 0.01, 0.37], P?=?0.044) were associated with greater ANP levels. In contrast, higher perceived social support was also associated with lower ANP levels, (β?=??0.19 [95 % CI ?0.05, ?0.41], P?=?0.010).

Conclusions

Psychosocial factors, including hostility, anger, and social support, are associated with varying ANP levels among middle-aged men, independent of cardiovascular and behavioral risk factors.