Coherent and incoherent ultrasound backscatter from cell aggregates

International audienceThe Effective Medium Theory (EMT) combined with the Structure Factor Model was recently developed to model the ultrasound backscatter from aggregating Red Blood Cells (RBCs) [Frances-chini, Metzger, Cloutier, IEEE UFFC, 2011]. The EMT assumes that aggregates can be treated as homogeneous effective spheres and the structure factor considers the interactions between the effective spheres. In this study, the EMT is further developed to decompose the differential backscattering cross section of a single cell aggregate into coherent and incoherent components. The coherent component corresponds to the average backscatter from the effective scatterer, and the incoherent component considers the fluctuation of the scattering wave around its average within the effective scatterer. A new theoretical expression for the incoherent component based on the structure factor is proposed and compared with another formulation based on the Gaussian direct correlation function. This theoretical improvement is assessed using computer simulations of ultrasound backscatter from aggregating cells. The consideration of the incoherent component based on the structure factor allows to approximate the simulations satisfactorily for a krag limit around 2, against a krag limit comprised between 1.07 and 1.47 with the former model considering only the coherent component

Sublingual grass allergen tablet immunotherapy provides sustained clinical benefit with progressive immunologic changes over 2 years

Background: This is an interim analysis of a randomized, double-blind, placebo-controlled phase III trial with 3 years of daily treatment with grass tablet immunotherapy (GRAZAX; ALK-Abello A/S, Horsholm, Denmark) or placebo, followed by 2 years of follow-up to assess the persistent efficacy. Objective: We sought to evaluate the efficacy and safety of specific immunotherapy with grass allergen tablets compared with placebo after treatment covering 2 consecutive grass pollen seasons. Methods: The interim analyses included 351 adult participants with moderate-to-severe allergic rhinoconjunctivitis caused by grass pollen. Participants were treated with active (n = 189) or placebo (n = 162) tablets for an average of 22 months. All participants were allowed to use symptomatic rescue medication. Results: The primary efficacy analysis showed highly significant mean reductions of 36% in rhinoconjunctivitis symptom score (P Conclusion: Grass allergen tablet immunotherapy showed progressive immunologic changes and highly significant efficacy over 2 years of continued treatment

Exposure to TARC alters beta2-adrenergic receptor signaling in human peripheral blood T lymphocytes

The beta(2)-adrenergic receptor (beta(2)-AR) negatively regulates T cell activity through the activation of the G(s)/adenylyl cyclase/cAMP pathway. beta(2)-AR desensitization, which can be induced by its phosphorylation, may have important consequences for the regulation of T cell function in asthma. In the present study we demonstrate that the C-C chemokine thymus and activation-regulated chemokine (TARC) impairs the ability of beta(2)-agonist fenoterol to activate the cAMP downstream effector cAMP-responsive element binding protein (CREB) in freshly isolated human T cells. The TARC-induced activation of Src kinases resulted in membrane translocation of both G protein-coupled receptor kinase (GRK) 2 and beta-arrestin. Moreover, TARC was able to induce Src-dependent serine phosphorylation of the beta(2)-AR as well as its association with GRK2 and beta-arrestin. Finally, in contrast to CREB, phosphorylation of Src and extracellular signal-regulated kinase was enhanced by fenoterol upon TARC pretreatment. In summary, we show for the first time that TARC exposure impairs beta(2)-AR function in T cells. Our data suggest that this is mediated by Src-dependent activation of GRK2, resulting in receptor phosphorylation, binding to beta-arrestin, and a switch from cAMP-dependent signaling to activation of the MAPK pathway. We propose that aberrant T cell control in the presence of endogenous beta-agonists promotes T cell-mediated inflammation in asthma

Comparison of a generic and a rhinitis-specific quality-of-life (QOL) instrument in patients with house dust mite allergy: Relationship between the SF-36 and rhinitis QOL questionnaire

Background: Generic and disease-specific quality-of-life (QOL) questionnaires are commonly used in subjects with allergic rhinitis (AR). AR, however, is closely associated with other disorders such as bronchial asthma and atopic dermatitis (AD). These co-morbid associations may have an effect on the inter-relation of generic and disease-specific QOL outcomes and the behaviour of this inter-relation in time. Objective: To unravel the inter-relationships between the outcome of a generic instrument (SF-36) and a disease-specific instrument (Rhinitis QOL Questionnaire (RQLQ)). Materials and methods: In the framework of a randomized clinical trial with respect to the efficacy of impermeable bedding covers in house dust mite (HDM) allergy, SF-36 and RQLQ were administered to 224 adults with AR and/or allergic asthma and/or AD at baseline and after 12 months of intervention. Regression analysis and canonical correlation were used to estimate overlap. Results: Overlap between SF-36 and RQLQ domains in terms of explained variance ranged from 6% to 56%. Canonical correlation yielded low coefficients (0.16-0.27). Moreover, both SF-36 and RQLQ s

Evaluation of impermeable covers for bedding in patients with allergic rhinitis

BACKGROUND: Encasing bedding in impermeable covers reduces exposure to house-dust mites, but the clinical benefit of this intervention as part of mite-avoidance measures for patients with allergic rhinitis is not known. We performed a multicenter, randomized, placebo-controlled trial of one year of use of impermeable bedding covers in the bedrooms of patients with rhinitis who were sensitized to house-dust mites to determine the effects on the signs and symptoms of disease. METHODS: Three participating university medical centers enrolled 279 patients with allergic rhinitis who were randomly assigned to receive impermeable or non-impermeable (control) covers for their mattress, pillow, and duvet or blanket. At the start of the study, all participants received information on general allergen-avoidance measures. The severity of rhinitis was measured on a rhinitis-specific visual-analogue scale and by means of a daily symptom score and nasal allergen provocation testing. We also measured the concentrations of Dermatophagoides pteronyssinus (Der p1) and D. farinae (Der f1) in dust from patients' mattresses, bedroom floors, and living-room floors at base line and after 12 months as a measure of the efficacy of the intervention. RESULTS: A total