Cerebral embolization associated with parenchymal seeding of the left atrial myxoma : Potential role of interleukin-6 and matrix metalloproteinases

Systemic embolization has been reported in up to 40% of patients with left atrial myxoma, half of them with cerebral involvement. However, development of intracerebral embolization associated with parenchymal seeding of the myxoma emboli is an extremely rare complication, with only 36 histologically diagnosed cases reported in the published literature. We describe a 69-year-old woman who arrived at the emergency service with hemiparesis associated with drug-resistant epilepsy and a medical history of resection of a left atrial myxoma 10 months previously. Cranial computed tomography revealed multiple large lesions of heterogeneous density and cystic components in the occipital lobes and posterior fossa parenchyma. Histopathological analyses after stereotactic biopsy of the occipital lesion revealed infiltrative myxoma cells with benign histological findings and uniform expression of calretinin similar to that of the primary cardiac myxoma. Additional immunohistochemical studies confirmed brain parenchymal seeding of the myxoma cells with strong expression of interleukin-6 (IL-6) and focal expression of matrix metalloproteinases-2 (MMP-2). Here, we discuss the clinicopathological features of intracerebral embolization of left atrial myxomas associated with progressive parenchymal seeding of the tumor emboli and the potential pathogenic role of IL-6 and MMPs.Peer reviewe

Computational model of blood flow in the aorto-coronary bypass graft

BACKGROUND: Coronary artery bypass grafting surgery is an effective treatment modality for patients with severe coronary artery disease. The conduits used during the surgery include both the arterial and venous conduits. Long- term graft patency rate for the internal mammary arterial graft is superior, but the same is not true for the saphenous vein grafts. At 10 years, more than 50% of the vein grafts would have occluded and many of them are diseased. Why do the saphenous vein grafts fail the test of time? Many causes have been proposed for saphenous graft failure. Some are non-modifiable and the rest are modifiable. Non-modifiable causes include different histological structure of the vein compared to artery, size disparity between coronary artery and saphenous vein. However, researches are more interested in the modifiable causes, such as graft flow dynamics and wall shear stress distribution at the anastomotic sites. Formation of intimal hyperplasia at the anastomotic junction has been implicated as the root cause of long- term graft failure. Many researchers have analyzed the complex flow patterns in the distal sapheno-coronary anastomotic region, using various simulated model in an attempt to explain the site of preferential intimal hyperplasia based on the flow disturbances and differential wall stress distribution. In this paper, the geometrical bypass models (aorto-left coronary bypass graft model and aorto-right coronary bypass graft model) are based on real-life situations. In our models, the dimensions of the aorta, saphenous vein and the coronary artery simulate the actual dimensions at surgery. Both the proximal and distal anastomoses are considered at the same time, and we also take into the consideration the cross-sectional shape change of the venous conduit from circular to elliptical. Contrary to previous works, we have carried out computational fluid dynamics (CFD) study in the entire aorta-graft-perfused artery domain. The results reported here focus on (i) the complex flow patterns both at the proximal and distal anastomotic sites, and (ii) the wall shear stress distribution, which is an important factor that contributes to graft patency. METHODS: The three-dimensional coronary bypass models of the aorto-right coronary bypass and the aorto-left coronary bypass systems are constructed using computational fluid-dynamics software (Fluent 6.0.1). To have a better understanding of the flow dynamics at specific time instants of the cardiac cycle, quasi-steady flow simulations are performed, using a finite-volume approach. The data input to the models are the physiological measurements of flow-rates at (i) the aortic entrance, (ii) the ascending aorta, (iii) the left coronary artery, and (iv) the right coronary artery. RESULTS: The flow field and the wall shear stress are calculated throughout the cycle, but reported in this paper at two different instants of the cardiac cycle, one at the onset of ejection and the other during mid-diastole for both the right and left aorto-coronary bypass graft models. Plots of velocity-vector and the wall shear stress distributions are displayed in the aorto-graft-coronary arterial flow-field domain. We have shown (i) how the blocked coronary artery is being perfused in systole and diastole, (ii) the flow patterns at the two anastomotic junctions, proximal and distal anastomotic sites, and (iii) the shear stress distributions and their associations with arterial disease. CONCLUSION: The computed results have revealed that (i) maximum perfusion of the occluded artery occurs during mid-diastole, and (ii) the maximum wall shear-stress variation is observed around the distal anastomotic region. These results can enable the clinicians to have a better understanding of vein graft disease, and hopefully we can offer a solution to alleviate or delay the occurrence of vein graft disease

BPIFB1 is a lung-specific autoantigen associated with interstitial lung disease.

Interstitial lung disease (ILD) is a complex and heterogeneous disorder that is often associated with autoimmune syndromes. Despite the connection between ILD and autoimmunity, it remains unclear whether ILD can develop from an autoimmune response that specifically targets the lung parenchyma. We examined a severe form of autoimmune disease, autoimmune polyglandular syndrome type 1 (APS1), and established a strong link between an autoimmune response to the lung-specific protein BPIFB1 (bactericidal/permeability-increasing fold-containing B1) and clinical ILD. Screening of a large cohort of APS1 patients revealed autoantibodies to BPIFB1 in 9.6% of APS1 subjects overall and in 100% of APS1 subjects with ILD. Further investigation of ILD outside the APS1 disorder revealed BPIFB1 autoantibodies present in 14.6% of patients with connective tissue disease-associated ILD and in 12.0% of patients with idiopathic ILD. The animal model for APS1, Aire⁻/⁻ mice, harbors autoantibodies to a similar lung antigen (BPIFB9); these autoantibodies are a marker for ILD. We found that a defect in thymic tolerance was responsible for the production of BPIFB9 autoantibodies and the development of ILD. We also found that immunoreactivity targeting BPIFB1 independent of a defect in Aire also led to ILD, consistent with our discovery of BPIFB1 autoantibodies in non-APS1 patients. Overall, our results demonstrate that autoimmunity targeting the lung-specific antigen BPIFB1 may contribute to the pathogenesis of ILD in patients with APS1 and in subsets of patients with non-APS1 ILD, demonstrating the role of lung-specific autoimmunity in the genesis of ILD

Circulating Matrix Metalloproteinase-9 Is Associated with Cardiovascular Risk Factors in a Middle-Aged Normal Population

Background: Elevated levels of circulating matrix metalloproteinase-9 (MMP-9) have been demonstrated in patients with established coronary artery disease (CAD). The aim of this study was to analyse levels of MMP-9 in a population free from symptomatic CAD and investigate their associations with cardiovascular (CV) risk factors, including C-reactive protein (CRP).   Methods: A cross-sectional study was performed in a population based random sample aged 45–69 (n = 345, 50% women). MMP-9 levels were measured in EDTA-plasma using an ELISA-method. CV risk factors were measured using questionnaires and standard laboratory methods. Results: Plasma MMP-9 was detectable in all participants, mean 38.9 ng/mL (SD 22.1 ng/mL). Among individuals without reported symptomatic CAD a positive association (p&lt;0.001) was seen, for both men and women, of MMP-9 levels regarding total risk load of eight CV risk factors i.e. blood pressure, dyslipidemia, diabetes, obesity, smoking, alcohol intake, physical activity and fruit and vegetable intake. The association was significant also after adjustment for CRP, and was not driven by a single risk factor alone. In regression models adjusted for age, sex, smoking, alcohol intake and CRP, elevated MMP-9 levels were independently positively associated with systolic blood pressure (p = 0.037), smoking (p&lt;0.001), alcohol intake (p = 0.003) and CRP (p&lt;0.001). The correlation coefficient between MMP-9 and CRP was r = 0.24 (p&lt;0.001).   Conclusions: In a population without reported symptomatic CAD, MMP-9 levels were associated with total CV risk load as well as with single risk factors. This was found also after adjustment for CRP  Original Publication: Peter Garvin, Lennart Nilsson, John Carstensen, Lena Jonasson and Margareta Kristenson, Circulating Matrix Metalloproteinase-9 Is Associated with Cardiovascular Risk Factors in a Middle-Aged Normal Population, 2008, PLoS ONE, (3), 3, e1774. http://dx.doi.org/10.1371/journal.pone.0001774 Licensee: Public Library of Science (PLoS) http://www.plos.org/</p