Methods We undertook AS1842856 mw a multicentre, double-blind, placebo-controlled trial at 81 centres in 13 countries between Nov 9, 2009, and Dec 5, 2011. Eligible patients were aged 12-74 years, had a history of recurrent severe asthma exacerbations, and had signs of eosinophilic inflammation. They were randomly assigned (in a 1:1:1:1 ratio) to receive one of three doses of intravenous mepolizumab (75 mg, 250 mg, or 750 mg) or matched placebo (100 mL 0.9% NaCl) with a central telephone-based system and computer-generated randomly permuted block schedule stratified by whether treatment with oral corticosteroids was required.

Patients received 13 infusions at 4-week intervals. The primary outcome was the rate of clinically significant asthma exacerbations, which were defined as validated episodes of acute asthma requiring treatment with oral corticosteroids, admission, or a visit to an emergency department. Patients, clinicians, and data analysts were masked to treatment assignment. Analyses were by intention to treat. This trial is registered with Foretinib datasheet ClinicalTrials.gov, number NCT01000506.

Findings

621 patients were randomised: 159 were assigned to placebo, 154 to 75 mg mepolizumab, 152 to 250 mg mepolizumab, and 156 to 750 mg mepolizumab. 776 exacerbations were deemed to be clinically significant. The rate of clinically significant exacerbations was 2.40 per patient per year in the placebo group, 1.24 in the 75 mg mepolizumab group (48% reduction, 95% CI 31-61%; p<0.0001), 1.46 in the 250 mg mepolizumab group (39% reduction, 19-54%; p=0.0005), and 1.15 in the 750 mg mepolizumab group (52% reduction, 36-64%; p<0.0001). Three patients died during the study,

but the deaths were not deemed to be related to treatment.

Interpretation Mepolizumab is an effective and well tolerated treatment that reduces the risk Fludarabine of asthma exacerbations in patients with severe eosinophilic asthma.”
“The regional distribution, laterality, and reliability of volumetric pulsed continuous arterial spin labeling (PCASL) measurements of cerebral blood flow (CBF) in cortical, subcortical, and cerebellar regions were determined in 10 normal volunteers studied on two occasions separated by 3 to 7 days. Regional CBF, normalized for global perfusion, was highly reliable when measured on separate days. Several regions showed significant lateral asymmetry; notably, in frontal regions CBF was greater in the right than left hemisphere, whereas left was greater than right in posterior regions. There was considerable regional variability across the brain, whereby the posterior cingulate and central and posterior precuneus cortices had the highest perfusion and the globus pallidus the lowest gray matter perfusion. The latter may be due to iron-induced T1 shortening affecting labeled spins and computed CBF signal.