Mast cells are thought to contribute to allergic airway disease. However, the role of mast cell-produced mediators, such as tumour necrosis factor (TNF), for the development of allergic airway disease is unclear.In order to define the role of mast cells in acute allergic airway disease two strains of mast celldeficient mice (KitW/Wv and KitW-sh/W-sh) were studied.Compared with their wild-type littermates, KitW/Wv and KitW-sh/W-sh mice developed significantly lower airway responsiveness to methacholine and less airway inflammation and goblet cell metaplasia, following sensitisation in the absence of adjuvant and airway challenge. Transfer of bone marrow-derived mast cells (BMMCs) from wild-type mice to KitW-sh/W-sh mice reconstituted both airway responsiveness and inflammation to levels similar to those in sensitised and challenged wild-type mice. In contrast, sensitised KitW-sh/W-sh mice reconstituted with BMMCs from TNF-deficient mice were still severely impaired in their ability to develop airway hyperresponsiveness, inflammation or goblet cell metaplasia following allergen challenge.The present results demonstrate the significance of mast cells in the development of airway disease and highlight the importance of mast cell-derived tumour necrosis factor in these responses.

Hemodynamics closely relating to those of volunteers were confirmed in sinus prostheses, believed to grant physiological valve function. Minor differences are presumably attributed to graft compliance and temporal resolution of the acquisition. Nevertheless, long-term deterioration of valve function as it was described for straight grafts could potentially be decelerated using sinus prostheses.

Purpose4D and 2D phase-contrast MRI (2D Flow MRI, 4D Flow MRI, respectively) are increasingly being used to noninvasively assess pulmonary hypertension (PH). The goals of this study were i) to evaluate whether established quantitative parameters in 2D Flow MRI associated with pulmonary hypertension can be assessed using 4D Flow MRI; ii) to compare results from 4D Flow MRI on a digital broadband 3T MR system with data from clinically established MRI-techniques as well as conservation of mass analysis and phantom correction and iii) to elaborate on the added value of secondary flow patterns in detecting PH.Methods11 patients with PH (4f, 63 ± 16y), 15 age-matched healthy volunteers (9f, 56 ± 11y), and 20 young healthy volunteers (13f, 23 ± 2y) were scanned on a 3T MR scanner (Philips Ingenia). Subjects were examined with a 4D Flow, a 2D Flow and a bSSFP sequence. For extrinsic comparison, quantitative parameters measured with 4D Flow MRI were compared to i) a static phantom, ii) 2D Flow acquisitions and iii) stroke volume derived from a bSSFP sequence. For intrinsic comparison conservation of mass-analysis was employed. Dedicated software was used to extract various flow, velocity, and anatomical parameters. Visualization of blood flow was performed to detect secondary flow patterns.ResultsOverall, there was good agreement between all techniques, 4D Flow results revealed a considerable spread. Data improved after phantom correction. Both 4D and 2D Flow MRI revealed concordant results to differentiate patients from healthy individuals, especially based on values derived from anatomical parameters. The visualization of a vortex, indicating the presence of PH was achieved in 9 /11 patients and 2/35 volunteers.DiscussionThis study confirms that quantitative parameters used for characterizing pulmonary hypertension can be gathered using 4D Flow MRI within clinically reasonable limits of agreement. Despite its unfavorable spatial and lesser temporal resolution and a non-neglible spread of results, the identification of diseased study participants was possible.

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