51 research outputs found

    This is the future: A reconstruction of the UK business web space (1996–2001)

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    This is the author accepted manuscript. The final version is available from SAGE via http://dx.doi.org/10.1177/1461444816643791Institute of Historical Researc

    Incidence and progression of mild aortic regurgitation after Tirone David reimplantation valve-sparing aortic root replacement

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    ObjectiveThe study objective was to determine whether recurrent or residual mild aortic regurgitation, which occurs after valve-sparing aortic root replacement, progresses over time.MethodsBetween 2003 and 2008, 154 patients underwent Tirone David-V valve-sparing aortic root replacement; 96 patients (62%) had both 1-year (median, 12 ± 4 months) and mid-term (62 ± 22 months) transthoracic echocardiograms available for analysis. Age of patients averaged 38 ± 13 years, 71% were male, 31% had a bicuspid aortic valve, 41% had Marfan syndrome, and 51% underwent aortic valve repair, predominantly cusp free margin shortening.ResultsForty-one patients (43%) had mild aortic regurgitation on 1-year echocardiogram. In 85% of patients (n = 35), mild aortic regurgitation remained stable on the most recent echocardiogram (median, 57 ± 20 months); progression to moderate aortic regurgitation occurred in 5 patients (12%) at a median of 28 ± 18 months and remained stable thereafter; severe aortic regurgitation developed in 1 patient, eventually requiring reoperation. Five patients (5%) had moderate aortic regurgitation at 1 year, which did not progress subsequently. Two patients (2%) had more than moderate aortic regurgitation at 1 year, and both ultimately required reoperation.ConclusionsAlthough mild aortic regurgitation occurs frequently after valve-sparing aortic root replacement, it is unlikely to progress over the next 5 years and should not be interpreted as failure of the valve-preservation concept. Further, we suggest that mild aortic regurgitation should not be considered nonstructural valve dysfunction, as the 2008 valve reporting guidelines would indicate. We need 10- to 15-year follow-up to learn the long-term clinical consequences of mild aortic regurgitation early after valve-sparing aortic root replacement

    Markers of extracellular matrix remodeling and systemic inflammation in patients with heritable thoracic aortic diseases

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    Background: In approximately 20% of patients with thoracic aortic aneurysms or dissections a heritable thoracic aortic disease (HTAD) is suspected. Several monogenic connective tissue diseases imply high risk of aortic disease, including both non-syndromic and syndromic forms. There are some studies assessing inflammation and extracellular matrix remodeling in patients with non-hereditary aortic disease, but such studies in patients with hereditary diseases are scarce. Aims: To quantify markers of extracellular matrix (ECM) and inflammation in patients with vascular connective tissue diseases versus healthy controls. Methods: Patients with Loeys-Dietz syndrome (LDS, n = 12), Marfan syndrome (MFS, n = 11), and familial thoracic aortic aneurysm 6 (FTAA6, n = 9), i.e., actin alpha 2 (ACTA2) pathogenic variants, were recruited. Exome or genome sequencing was performed for genetic diagnosis. Several markers of inflammation and ECM remodeling were measured in plasma by enzyme immunoassays. Flow cytometry of T-cell subpopulations was performed on a subgroup of patients. For comparison, blood samples were drawn from 14 healthy controls. Results: (i) All groups of HTAD patients had increased levels matrix metalloproteinase-9 (MMP-9) as compared with healthy controls, also in adjusted analyses, reflecting altered ECM remodeling. (ii) LDS patients had increased levels of pentraxin 3 (PTX3), reflecting systemic inflammation. (iii) LDS patients have increased levels of soluble CD25, a marker of T-cell activation. Conclusion: Our data suggest that upregulated MMP-9, a matrix degrading enzyme, is a common feature of several subgroups of HTAD. In addition, LDS patients have increased levels of PTX3 reflecting systemic and in particular vascular inflammation

    Inflammation and Mechanical Stress Stimulate Osteogenic Differentiation of Human Aortic Valve Interstitial Cells

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    Background: Aortic valve calcification is an active proliferative process, where interstitial cells of the valve transform into either myofibroblasts or osteoblast-like cells causing valve deformation, thickening of cusps and finally stenosis. This process may be triggered by several factors including inflammation, mechanical stress or interaction of cells with certain components of extracellular matrix. The matrix is different on the two sides of the valve leaflets. We hypothesize that inflammation and mechanical stress stimulate osteogenic differentiation of human aortic valve interstitial cells (VICs) and this may depend on the side of the leaflet.Methods: Interstitial cells isolated from healthy and calcified human aortic valves were cultured on collagen or elastin coated plates with flexible bottoms, simulating the matrix on the aortic and ventricular side of the valve leaflets, respectively. The cells were subjected to 10% stretch at 1 Hz (FlexCell bioreactor) or treated with 0.1 μg/ml lipopolysaccharide, or both during 24 h. Gene expression of myofibroblast- and osteoblast-specific genes was analyzed by qPCR. VICs cultured in presence of osteogenic medium together with lipopolysaccharide, 10% stretch or both for 14 days were stained for calcification using Alizarin Red.Results: Treatment with lipopolysaccharide increased expression of osteogenic gene bone morphogenetic protein 2 (BMP2) (5-fold increase from control; p = 0.02) and decreased expression of mRNA of myofibroblastic markers: α-smooth muscle actin (ACTA2) (50% reduction from control; p = 0.0006) and calponin (CNN1) (80% reduction from control; p = 0.0001) when cells from calcified valves were cultured on collagen, but not on elastin. Mechanical stretch of VICs cultured on collagen augmented the effect of lipopolysaccharide. Expression of periostin (POSTN) was inhibited in cells from calcified donors after treatment with lipopolysaccharide on collagen (70% reduction from control, p = 0.001), but not on elastin. Lipopolysaccharide and stretch both enhanced the pro-calcific effect of osteogenic medium, further increasing the effect when combined for cells cultured on collagen, but not on elastin.Conclusion: Inflammation and mechanical stress trigger expression of osteogenic genes in VICs in a side-specific manner, while inhibiting the myofibroblastic pathway. Stretch and lipopolysaccharide synergistically increase calcification

    Bjarne K. H. Semb : The contriver of the first implantation of a total artificial heart in Europe

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    In 1985, the surgical team led by Bjarne Semb implanted the first total artificial heart (TAH) in Europe, and the following year the first successful bridge to transplant in Europe using the Symbion J-7/100 TAH. Together with the clinical experiences of colleagues in the United States, these early cases preceded the subsequent development of scores of mechanical assist devices to treat advanced heart failure. Semb proved to have the pioneering spirit needed to use the early generation of a TAH, but these early implants also generated much controversy in the medical community as well as the general public

    5D MRI - Cardiac and respiratory time-resolved volume imaging

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    Respiratory motion is often a source of artifacts in cardiovascular imaging, but may also convey important physiological information. To improve our understandin

    4D Flow MRI quantification of blood flow patterns, turbulence and pressure drop in normal and stenotic prosthetic heart valves

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    Purpose: To assess valvular flow characteristics and pressure drop in a variety of normal and stenotic prosthetic heart valves (PHVs) using 4D Flow MRI. Materials and methods: In-vitro flow phantoms with four different PHVs were studied: Medtronic-Hall tilting disc, St. Jude Medical standard bileaflet (STJM), Medtronic CoreValve Evolut R and Edwards SAPIEN 3. The valvular flow characteristics were investigated in normal and stenotic PHVs by using 4D Flow MRI. Results: The results showed that each valve provided a different amount of signal loss in the 4D Flow MRI. The defect size of the signal loss from each valve was 37.5 mm, 39.0 mm, 37.5 mm and 51.0 mm for the Tilting disk, STJM, SAPIEN 3 and CoreValve, respectively. The 4D Flow MRI-based estimation of the elevation of the pressure drop through the stenotic PHV using both Bernoulli-based and turbulence-based methods correlated well with the true values for the Tilting disc, STJM and SAPIEN 3 valve. However, the obstructive hemodynamics in the stenotic CoreValve was not clearly identified due to the large signal void from the long struts, resulting in a severe underestimation of the pressure drop using 4D Flow MRI. Conclusion: The Tilting disc, STJM and SAPIEN 3 valves provided reasonable estimates of peak velocity, turbulence production and the corresponding pressure drop. In contrast, the large strut of the CoreValve and corresponding signal void prevented accurate measurements of the velocity and turbulence production; therefore, 4D Flow MRI prediction of the pressure drop through the CoreValve was not feasible.Funding Agencies|European Union Seventh Framework Programme, European-Union (FP7/2007-2013) [310612]; Swedish Research Council, Sweden [2013-6077, 2014-6191]; Basic Science Research Program through the National Research Foundation of Korea, South Korea (NRF) - Ministry of Education [2018R1D1A1A02043249]</p
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