Intrapulmonary 3He gas distribution depending on bolus size and temporal bolus placement

OBJECTIVE: Dynamic ventilation (3)He-MRI is a new method to assess pulmonary gas inflow. As differing airway diameters throughout the ventilatory cycle can influence gas inflow this study intends to investigate the influence of volume and timing of a He gas bolus with respect to the beginning of the tidal volume on inspiratory gas distribution. MATERIALS AND METHODS: An ultrafast 2-dimensional spoiled gradient echo sequence (temporal resolution 100 milliseconds) was used for dynamic ventilation (3)He-MRI of 11 anesthetized and mechanically ventilated pigs. The applied (3)He gas bolus was varied in volume between 100 and 200 mL. A 150-mL bolus was varied in its application time after the beginning of the tidal volume between 0 and 1200 milliseconds. Signal kinetics were evaluated using an in-house developed software after definition of parameters for the quantitative description of (3)He gas inflow. RESULTS: The signal rise time (time interval between signal in the parenchyma reaches 10% and 90% of its maximum) was prolonged with increasing bolus volume. The parameter was shortened with increasing delay of (3)He application after the beginning of the tidal volume. Timing variation as well as volume variation showed no clear interrelation to the signal delay time 10 (time interval between signal in the trachea reaches 50% of its maximum and signal in the parenchyma reaches 10% of its maximum). CONCLUSIONS: Dynamic ventilation (3)He-MRI is able to detect differences in bolus geometry performed by volume variation. Pulmonary gas inflow as investigated by dynamic ventilation (3)He-MRI tends to be accelerated by an increasing application delay of a (3)He gas bolus after the beginning of the tidal volume.

Treatment of patients with the hypereosinophilic syndrome with mepolizumab

BACKGROUND: The hypereosinophilic syndrome is a group of diseases characterized by persistent blood eosinophilia, defined as more than 1500 cells per microliter with end-organ involvement and no recognized secondary cause. Although most patients have a response to corticosteroids, side effects are common and can lead to considerable morbidity. METHODS: We conducted an international, randomized, double-blind, placebo-controlled trial evaluating the safety and efficacy of an anti-interleukin-5 monoclonal antibody, mepolizumab, in patients with the hypereosinophilic syndrome. Patients were negative for the FIP1L1-PDGFRA fusion gene and required prednisone monotherapy, 20 to 60 mg per day, to maintain a stable clinical status and a blood eosinophil count of less than 1000 per microliter. Patients received either intravenous mepolizumab or placebo while the prednisone dose was tapered. The primary end point was the reduction of the prednisone dose to 10 mg or less per day for 8 or more consecutive weeks. RESULTS: The primary end point was reached in 84% of patients in the mepolizumab group, as compared with 43% of patients in the placebo group (hazard ratio, 2.90; 95% confidence interval [CI], 1.59 to 5.26; P<0.001) with no increase in clinical activity of the hypereosinophilic syndrome. A blood eosinophil count of less than 600 per microliter for 8 or more consecutive weeks was achieved in 95% of patients receiving mepolizumab, as compared with 45% of patients receiving placebo (hazard ratio, 3.53; 95% CI, 1.94 to 6.45; P<0.001). Serious adverse events occurred in seven patients receiving mepolizumab (14 events, including one death; mean [+/-SD] duration of exposure, 6.7+/-1.9 months) and in five patients receiving placebo (7 events; mean duration of exposure, 4.3+/-2.6 months). CONCLUSIONS: Our study shows that treatment with mepolizumab, an agent designed to target eosinophils, can result in corticosteroid-sparing for patients negative for FIP1L1-PDGFRA who have the hypereosinophilic syndrome. (ClinicalTrials.gov number, NCT00086658 [ClinicalTrials.gov].).

Pericyte migration: a novel mechanism of pericyte loss in experimental diabetic retinopathy

OBJECTIVE: The mechanism underlying pericyte loss during incipient diabetic retinopathy remains controversial. Hyperglycemia induces angiopoietin-2 (Ang-2) transcription, which modulates capillary pericyte coverage. In this study, we assessed loss of pericyte subgroups and the contribution of Ang-2 to pericyte migration. RESEARCH DESIGN AND METHODS: Numbers of total pericytes and their subgroups were quantified in retinal digest preparations of spontaneous diabetic XLacZ mice. Pericytes were divided into subgroups according to their localization, their position relative to adjacent endothelial cells, and the expression of LacZ. The contribution of Ang-2 to pericyte migration was assessed in Ang-2 overexpressing (mOpsinhAng2) and deficient (Ang2LacZ) mice. RESULTS: Pericyte numbers were reduced by 16% (P < 0.01) in XLacZ mice after 6 months of diabetes. Reduction of pericytes was restricted to pericytes on straight capillaries (relative reduction 27%, P < 0.05) and was predominantly observed in LacZ-positive pericytes (-20%, P < 0.01). Hyperglycemia increased the numbers of migrating pericytes (69%; P < 0.05), of which the relative increase due to diabetes was exclusively in LacZ-negative pericytes, indicating reduced adherence to the capillaries (176%; P < 0.01). Overexpression of Ang-2 in nondiabetic retinas mimicked diabetic pericyte migration of wild-type animals (78%; P < 0.01). Ang-2 deficient mice completely lacked hyperglycemia-induced increase in pericyte migration compared with wild-type littermates. CONCLUSIONS: Diabetic pericyte loss is the result of pericyte migration, and this process is modulated by the Ang-Tie system.

1509 - Johannes Calvin - 2009. Sein Wirken in Kirche und Gesellschaft. Essays zum 500. Geburtstag

Welche bleibenden Impulse haben Johannes Calvin und der Calvinismus Kirche und Gesellschaft bis heute gegeben? Mit dieser Frage beschäftigen sich anlässlich des 500. Geburtstags des Genfer Reformators die Autorinnen und die Autoren der vorliegenden Beiträge anhand ausgewählter theologischer und wirkungsgeschichtlicher Themen. Gleichzeitig bieten sie eine grundlegende und allgemein verständliche Einführung in Calvins Leben und Theologie, in seine kontinuierliche Relevanz für kirchliche, gesellschaftliche und politische Fragen sowie in die Geschichte der Reformation in der Schweiz und weltweit. Sie blenden dabei auch die kritischen Anfragen an Calvin nicht aus. Der im Auftrag des Schweizerischen Evangelischen Kirchenbunds herausgegebene Sammelband ist eine wissenschaftlich fundierte, leserfreundliche Einführung, die Fragestellungen anregt, Perspektiven eröffnet und Austausch ermöglicht. Mit Beiträgen von Philip Benedict, James D. Bratt, Emidio Campi, Eva-Maria Faber, Eric Fuchs, Wulfert de Greef, Christopher L. Elwood, Ulrich H. J. Körtner, Christian Link, Christian Moser, Andrew Pettegree, Christoph Strohm, Mario Turchetti