In generalized myasthenia gravis (MG) patients without detectable acetylcholine receptor (AChR) antibodies (SNMG), the thymus is often reported as "normally involuted." We analyzed thymic compartments in 67 patients with generalized MG, with AChR antibodies (AChR+, n = 23), with muscle-specific kinase (MuSK) antibodies (MuSK+, n = 14) or with neither (MuSK-, n = 30), and in 11 non-MG controls. Four of 14 MuSK+ thymi had rare small germinal centers, but overall they were not different from age-matched controls. However, approximately 75% MuSK- samples showed lymph node-type infiltrates similar to those in AChR+ patients, but with fewer germinal centers. These variations may explain some apparent differences in responses to thymectomy in SNMG.

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Anti-neutrophil cytoplasmic antibodies (c-ANCA) targeting proteinase 3 (PR3) are implicated in the pathogenesis of Wegener's granulomatosis (WG). Fulminant disease can present as acute lung injury (ALI).In this study, a model of ALI in WG was developed using isolated rat lungs. Isolated human polymorphonuclear leukocytes (PMNs) were primed with tumour necrosis factor (TNF) to induce surface expression of PR3.Co-perfusion of TNF-primed neutrophils and monoclonal anti-PR3 antibodies induced a massive weight gain in isolated lungs. This effect was not observed when control immunoglobulin G was co-perfused with TNF-primed PMNs. The c-ANCA-induced oedema formation was paralleled by an increase in the capillary filtration coefficient as a marker of increased pulmonary endothelial permeability. In contrast, pulmonary artery pressure was not affected. In the presence of the oxygen radical scavenger superoxide dismutase and a NADPH oxidase inhibitor, c-ANCAinduced lung oedema could be prevented. Inhibition of neutrophil elastase was equally effective in preventing c-ANCA-induced lung injury.In conclusion, anti-PR3 antibodies induced neutrophil mediated, elastase-and oxygen radicaldependent ALI in the isolated lung. This experimental model supports the hypothesis of a pathogenic role for c-ANCA in WG and offers the possibility of the development of therapeutic strategies for the treatment of lung injury in fulminant WG.

There is an increased body of evidence to suggest that the vasa vasorum play a major role in the progression and complications of vulnerable plaque leading to acute coronary syndrome. We propose the concept that detecting changes in the flow in the vascular wall by IVUS signals can quantify the presence of vasa vasorum. The results obtained in porcine model of atherosclerosis suggest that IVUS-based estimates of blood flow in the arterial wall can be used in vivo in a clinical research setting to establish the density of vasa vasorum as an indicator of plaque vulnerability.

Objective-This study evaluated the influence of voxel size on its ability to discriminate calcium from iron deposits in ex vivo coronary arteries.Methods-Postmortem human coronary arteries underwent multislice computed tomographic scan at 600-μm 3 voxel size to provide an index of computed tomography (CT) image noise and synchrotron-based micro-CT at 4-μm 3 voxel size to provide data for generating a range of voxel sizes 4 to 600 μm 3 after grayscale noise was added to the projection images before reconstruction so as to mimic the effect of retaining the same radiation exposure involved in the multislice computed tomographic scan.Results-At voxel sizes of 20 μm 3 or smaller, iron deposits could be identified based on CT grayscale value. Voxels of 100 μm 3 or larger cannot resolve nor distinguish iron deposits from calcifications by virtue of CT grayscale value.Conclusions-Clinical CT scanners cannot be expected to discriminate iron deposits from calcifications by their CT value alone in the arterial wall. Keywordsatherosclerosis; dual-source CT; human coronary arteries; imaging; micro-CT Acute myocardial infarction is often caused by the rupture of noncalcified, advanced atherosclerotic plaques. 1 As the culprit lesion seems to be largely associated with noncalcified plaques, some characteristic other than calcification, detectable by minimally invasive means, is needed to detect plaques that might lead to acute coronary occlusion. A candidate for this detection is the presence of prior hemorrhage into the plaque. Such hemorrhage would result in micro-opacities due to the iron derived from the hemoglobin in the red blood cells. Because iron is more radiopaque than the calcium deposits, this is a candidate for discrimination of iron [5][6][7] have been developed and used to explore how well atherosclerotic lesions can be detected and classified in vivo or experimentally. The relation of fibro-calcified lesions, as determined by CT using the Agatston score, and cardiovascular events has been demonstrated. [8][9][10] However, the validity of the CT grayscale values of small opacities in the arterial wall depends in part on the partial volume effect of the detector pixel size (and CT image voxel size), x-ray beam hardening because of torso diameter, and the increased quantum noise that occurs when a voxel size is decreased without suitable increase of radiation exposure. The presence of intravascular contrast agent in the lumen may further decrease the ability to detect and distinguish iron and calcium deposits.This study includes an attempt at quantifying the impact of voxel partial volume effect on the ability to discriminate the iron from calcium deposits in the presence of intravascular contrast medium. Micro-CT studies in atherosclerotic mice 11 have shown the ability to detect and discriminate iron and calcium deposits in the wall of the aorta, both by virtue of the size of the opacities (the area of individual iron deposits within a single CT slice being <100 μm 2 and calcium deposits being >1000 μm ...