Intergenerational transfer of blood pressure knowledge and screening: a school-based hypertension awareness program in Singapore.

OBJECTIVE: This study aims to examine the efficacy of a hypertension awareness education program in Singapore in reaching out to a wider population of diverse racial and intergenerational cohorts by dispatching grade five children as information intermediaries to their immediate and extended family members. METHOD: After receiving structured instruction and training on blood pressure screening, students were requested to share knowledge gained in school with their family members at home and practice blood pressure measurement on family volunteers. We assessed pre- and post-program blood pressure knowledge change, attitude toward screening, and the diffusion of blood pressure information. One adult family member was also asked to complete a short survey at the program end. RESULTS: A comparison of the students' (final n = 3926) pre- and post-program survey data showed that knowledge and attitudes towards knowledge sharing improved after participating in the program. The post-program survey also revealed that students generally felt confident and displayed positive attitudes in performing blood pressure screening on family members. On average, each student practiced blood pressure measurement on 3.04 people. Female family members were more likely to be targeted for knowledge sharing and screening than male family members. The family members' survey revealed positive attitudes towards screening, but family members were not confident about getting their measurements done regularly. CONCLUSION: The program met its objectives in raising the awareness of grade five children and provision of knowledge. It also met the larger objective of raising hypertension awareness in a wider population, especially those who otherwise might not directly receive health education and blood pressure screening.

A novel coronary artery bypass graft design of sequential anastomoses.

In this paper, the hemodynamics in a three-dimensional out-of-plane sequential bypass graft model is first investigated. Based on the advantageous flow characteristics observed within the side-to-side (STS) anastomosis in the sequential bypass graft simulation, a new CABG coupled-sequential anastomosis configuration is designed, entailing coupled STS and end-to-side (ETS) anastomotic components. In this new CABG design, the flow fields and distributions of various wall shear stress parameters within the STS and ETS anastomotic regions are studied, and compared to those of the conventional distal anastomosis, by means of computational fluid dynamics simulation of pulsatile Newtonian blood flow. Simulation results demonstrate that the new sequential anastomoses model provides: (i) a more uniform and smooth flow at the ETS anastomosis, without any stagnation point on the artery bed and vortex formation in the heel region of the ETS anastomosis within the coronary artery; (ii) a spare route for the blood flow to the coronary artery, to avoid re-operation in case of re-stenosis in either of the anastomoses; and (iii) improved distribution of hemodynamic parameters at the coronary artery bed and in the heel region of the ETS anastomosis, with more moderate shear stress indices. These advantages of the new design over the conventional ETS anastomosis are influenced by the occlusion ratio of the native coronary artery, and are most prominent when the proximal segment of the coronary artery is fully occluded. By varying the design parameters of the anastomotic angle and distance between the two anastomoses, the superior coupled STS-ETS anastomoses design is found to have the anastomotic angle of 30° and 30 mm distance between the two (STS and ETS) components.

Numerical investigation and identification of susceptible sites of atherosclerotic lesion formation in a complete coronary artery bypass model.

As hemodynamics is widely believed to correlate with anastomotic stenosis in coronary bypass surgery, this paper investigates the flow characteristics and distributions of the hemodynamic parameters (HPs) in a coronary bypass model (which includes both proximal and distal anastomoses), under physiological flow conditions. Disturbed flows (flow separation/reattachment, vertical and secondary flows) as well as regions of high oscillatory shear index (OSI) with low wall shear stress (WSS), i.e., high-OSI-and-low-WSS and low-OSI-and-high-WSS were found in the proximal and distal anastomoses, especially at the toe and heel regions of distal anastomosis, which indicate highly suspected sites for the onset of the atherosclerotic lesions. The flow patterns found in the graft and distal anastomoses of our model at deceleration phases are different from those of the isolated distal anastomosis model. In addition, a huge significant difference in segmental averages of HPs was found between the distal and proximal anastomoses. These findings further suggest that intimal hyperplasia would be more prone to form in the distal anastomosis than in the proximal anastomosis, particularly along the suture line at the toe and heel of distal anastomosis.

Validation of numerical simulation with PIV measurements for two anastomosis models.

Hemodynamics is widely believed to influence coronary artery bypass graft (CABG) stenosis. Although distal anastomosis has been extensively investigated, further studies on proximal anastomosis are still necessary, as the extent and initiation of the stenosis process may be influenced by the flow of the proximal anastomosis per se. Therefore, in this study, two models (i.e. 90 degrees and 135 degrees anastomotic models) were designed and constructed to simulate a proximal anastomosis of CABG for the left and right coronary arteries, respectively. Flow characteristics for these models were studied experimentally in order to validate the simulation results found earlier. PIV measurements were carried out on two Pyrex glass models, so that the disturbed flow (stagnation point, flow separation and vortex) found in both proximal anastomosis models using numerical simulation, could be verified. Consequently, a fair agreement between numerical and experimental data was observed in terms of flow characteristics, velocity profiles and wall shear stress (WSS) distributions under both steady and pulsatile flow conditions. The discrepancy was postulated to be due to the difference in detailed geometry of the physical and computational models, due to manufacturing limitations. It was not possible to reproduce the exact shape of the computational model when making the Pyrex glass model. The analysis of the hemodynamic parameters based on the numerical simulation study also suggested that the 135 degrees proximal anastomosis model would alleviate the potential of intimal thickening and/or atherosclerosis, more than that of a 90 degrees proximal anastomosis model, as it had a lower variation range of time-averaged WSS and the lower segmental average of WSSG.

Factors influencing radial artery size.

Size matching of radial artery conduits to coronary arteries is important as it affects the long-term patency. However, factors affecting radial artery size have not been adequately investigated. We retrospectively reviewed 327 consecutive patients who had duplex ultrasonography of their radial arteries over a 2-year period. There were 225 men and 102 women. The mean radial artery size was 2.45 +/- 0.54 mm. The factors found to positively affect the size of the radial artery were sex, hypertension, and hyperlipidemia. Diabetes mellitus and age were found to negatively affect radial artery size. Renal disease, race, and smoking did not significantly influence the size of the radial artery. However, as the R squared of this model was insignificant, further studies need to be undertaken to determine other factors that may influence radial artery size.

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.

Ex vivo differentiation of human adult bone marrow stem cells into cardiomyocyte-like cells.

Bone marrow mesenchymal stem cells have been shown to transdifferentiate into cardiomyocytes after 5-azacytidine treatment or co-culturing with rodent cardiomyocytes. We investigate if adult human bone marrow stem cells can be differentiated ex vivo into cardiomyocyte-like cells (CLCs) independent of cytotoxic agents or co-culturing technique. Sternal bone marrow was collected from 16 patients undergoing coronary artery bypass surgery. Mesenchymal stem cells were differentiated in a cardiomyogenic differentiation medium containing insulin, dexamethasone, and ascorbic acid. Differentiation towards CLCs was determined by induced expression of cardiomyocyte-specific proteins. Differentiated CLCs expressed multiple structural and contractile proteins that are associated with cardiomyocytes. Thin filament associated myofibrillar proteins were detected early in the cells, with cardiac troponin I, sarcomeric tropomyosin, and cardiac titin among the first expressed. Some CLCs were found to develop into a nascent cardiomyocyte phenotype with cross-striated myofibrils characterized by alpha-actinin-positive Z bands after 4-5 passages in differentiated culture. These lineage-defined CLCs may be potentially useful for repairing damaged myocardium.

ABCA1 gene polymorphisms and their associations with coronary artery disease and plasma lipids in males from three ethnic populations in Singapore.

Mutations in the ATP-binding cassette transporter ABCA1 underlie Tangier disease and familial hypoalphaliproteinemia (FHA), disorders that are characterised by reduced high-density lipoprotein-cholesterol (HDL-C) concentration and cholesterol efflux, and increased coronary artery disease (CAD). We explored if polymorphisms in the ABCA1 gene are associated with CAD and variations in plasma lipid levels, especially HDL-C, and whether the associations may depend on ethnicity. Male cases and controls from the Singapore Chinese, Malay and Indian populations were genotyped for five ABCA1 single nucleotide polymorphisms. Various single-locus frequency distribution differences between cases and controls were detected in different ethnic groups: the promoter -14C>T in Indians, exon 18 M883I in Malays, and 3'-untranslated (UTR) region 8994A>G in Chinese. For the Malay population, certain haplotypes carrying the I825- A (exon 17) and M883- G alleles were more frequent among cases than controls, whereas the converse was true for the alternative configuration of V825- G and I883- A, and this association was reinforced in multi-locus disequilibrium analysis that utilized genotypic data. In the healthy controls, associations were found for -14C>T genotypes with HDL-C in Chinese; 237indelG (5'UTR) with apolipoprotein A1 (apoA1) in Malays and total cholesterol (TC) in Indians; M883I with lipoprotein(a) [Lp(a)] in Malays and apolipoprotein B (apoB) in Chinese; and 8994A>G with Lp(a) in Malays, and TC, low-density lipoprotein-cholesterol (LDL-C) as well as apoB in Indians. While genotype-phenotype associations were not reproduced across populations and loci, V825I and M883I were clearly associated with CAD status in Malays with no effects on HDL-C or apoA1.

A limited sampling strategy for the estimation of 12-hour Neoral systemic drug exposure in heart transplant recipients.

BACKGROUND: Therapeutic drug monitoring of cyclosporine in heart transplant patients is used to monitor therapy and prevent rejection. Of the various methods available for performing therapeutic drug monitoring of cyclosporine, the method of limited sampling strategy for area under the concentration-time curve profiling has been used most widely recently. The process of identifying sparse data points to predict area under the concentration-time curve is essentially a variable selection problem, with the variables being the drug concentrations at the various timepoints. Although fitting more variables into a model will typically allow for a better prediction of area under the concentration-time curve, improving the prediction has to be traded-off against the desirability of using as few timepoints as possible. The objective of this study was thus to formulate a model that would provide a good prediction of area under the concentration-time curve based on a limited number of sampling points. METHODS: We studied 15 stable heart transplant patients (11 Chinese and 4 Indians). All patients were receiving Neoral-based immunosuppression. Whole blood samples for area under the concentration-time curve analysis were obtained at the following timepoints: pre-dose (C(0h)) and at 1, 2, 3, 4, 6 and 12 hours (C(1h), C(2h), C(3h), C(4h), C(6h), C(12h), respectively) post-dose during the first dosing interval. The linear trapezoidal rule was used to calculate the area under the concentration-time curve (AUC) from time 0 h to 12 h. Various limited sampling strategies, as well as Keown's formula, which was derived in renal transplant patients and used C(0h) and C(2h), were compared based on their capacity for reducing total error squared. RESULTS: C(4h) was found to be the single most predictive timepoint and explained 95.3% of AUC(0-12) variation. C(0h) and C(12h) explained 60% and 75.7% of the variation in AUC(0-12), respectively. The best 2-variable model identified by stepwise selection procedures included C(1h) and C(4h) as predictors, explaining 97.3% of the variation in total area under the concentration-time curve from time 0 h to 12 h. Using Keown's algorithm, the R(2) was only 80.9%. CONCLUSION: We recommend using C(1h) and C(4h) as surrogate markers of area under the concentration-time curve from time 0 h to 12 h in our heart transplant patients. Because C(1h) and C(4h) represent timepoints within the zone of highest variability for Neoral's absorption phase, a model incorporating these timepoints would be able to explain a greater degree of variability associated with the Neoral absorption profile.