Increased platelet-derived microparticles in the coronary circulation of percutaneous transluminal coronary angioplasty patients

Platelet-derived microparticles that are produced during platelet activation are capable of adhesion and aggregation. Endothelial trauma that occurs during percutaneous transluminal coronary angioplasty (PTCA) may support platelet-derived microparticle adhesion and contribute to development of restenosis. We have previously reported an increase in platelet-derived microparticles in peripheral arterial blood with angioplasty. This finding raised concerns regarding the role of plateletderived microparticles in restenosis, and therefore the aim of this study was to monitor levels in the coronary circulation. The study population consisted of 19 angioplasty patients. Paired coronary artery and sinus samples were obtained following heparinization, following contrast administration, and subsequent to all vessel manipulation. Platelet-derived microparticles were identified with an anti-CD61 (glycoprotein IIIa) fluorescence-conjugated antibody using flow cytometry. There was a significant decrease in arterial platelet-derived microparticles from heparinization to contrast administration (P 0.001), followed by a significant increase to the end of angioplasty (P 0.004). However, there was no significant change throughout the venous samples. These results indicate that the higher level of platelet-derived microparticles after angioplasty in arterial blood remained in the coronary circulation. Interestingly, levels of thrombin–antithrombin complexes did not rise during PTCA. This may have implications for the development of coronary restenosis post-PTCA, although this remains to be determined.

Increased generation of platelet-derived microparticles following percutaneous transluminal coronary angioplasty

Platelet-derived microparticles that are produced during platelet activation bind to traumatized endothelium. Such endothelial injury occurs during percutaneous transluminal coronary angioplasty. Approximately 20% of these patients subsequently develop restenosis, although this is improved by treatment with the anti-platelet glycoprotein IIb/IIIa receptor drug abciximab. As platelet activation occurs during angioplasty, it is likely that platelet-derived microparticles may be produced and hence contribute to restenosis. This study population consisted of 113 angioplasty patients, of whom 38 received abciximab. Paired peripheral arterial blood samples were obtained following heparinization and subsequent to all vessel manipulation. Platelet-derived microparticles were identified using an anti-CD61 (glycoprotein IIIa) fluorescence-conjugated antibody and flow cytometry. Baseline clinical characteristics between patient groups were similar. The level of platelet-derived microparticles increased significantly following angioplasty in the group without abciximab (paired t test, P 0.019). However, there was no significant change in the level of platelet-derived microparticles following angioplasty in patients who received abciximab, despite requiring more complex angioplasty procedures. In this study, we have demonstrated that the level of platelet-derived microparticles increased during percutaneous transluminal coronary angioplasty, with no such increase with abciximab treatment. The increased platelet-derived microparticles may adhere to traumatized endothelium, contributing to re-occlusion of the arteries, but this remains to be determined.

Demographics and survivial of a cohort of blood and breast cancer patients who developed heart failure following cancer treatment

Background/Aim: Cardiotoxicity resulting in heart failure is a devastating complication of cancer therapy. It is possible that a patient may survive cancer only to develop heart failure (HF), which is more deadly than cancer. The aim of this project was to profile the characteristics of patients at risk of cancer treatment induced heart failure. Methods: Linked Health Data Analysis of Queensland Cancer Registry (QCR) from 1996-2009, Death Registry and Hospital Administration records for HF and chemotherapy admissions were reviewed. Index heart failure admission must have occurred after the date of cancer registry entry. Results: A total of 15,987 patients were included in this analysis; 1,062 (6.6%) had chemotherapy+HF admission (51.4% Female) and 14,925 (93.4%) chemotherapy_no HF admission. Median age of chemotherapy+HF patients was 67 years (IQR 58 to 75) vs. 54 years (IQR 44 to 64) for chemotherapy_no HF admission. Chemotherapy+HF patients had increased risk of all cause mortality (HR 2.79 [95% CI 2.58-3.02] and 1.67 [95% CI, 1.54 to 1.81] after adjusting for age, sex, marital status, country of birth, cancer site and chemotherapy dose). Index HF admission occurred within one year of cancer diagnosis in 47% of HF patients with 80% of patinets having there index admission with 3 years. The number of chemotherapy cycles was not associated with significant reduction in survival time in chemotherapy+HF patients. Mean survival for heart failure patients was 5.3 years (95% CI, 4.99 - 5.62) vs.9.57 years (95% CI, 9.47-9.68) for chemotherapy_no HF admission patients. Conclusion: All-cause mortality was 67% higher in patients diagnosed with HF following chemotherapy in adjusted analysis for covariates. Methods to improve and better coordinate of the interdisciplinary care for cancer patients with HF involving cardiologists and oncologists are required, including evidence-based guidelines for the comprehensive assessment, monitoring and management of this cohort.

Signaling pathway genes for blood pressure, folate and cholesterol levels among hypertensives : an epistasis analysis

Irregular atrial pressure, defective folate and cholesterol metabolism contribute to the pathogenesis of hypertension. However, little is known about the combined roles of the methylenetetrahydrofolate reductase (MTHFR), apolipoprotein-E (ApoE) and angiotensin-converting enzyme (ACE) genes, which are involved in metabolism and homeostasis. The objective of this study is to investigate the association of the MTHFR 677 C>T and 1298A>C, ACE insertion–deletion (I/D) and ApoE genetic polymorphisms with hypertension and to further explore the epistasis interactions that are involved in these mechanisms. A total of 594 subjects, including 348 normotensive and 246 hypertensive ischemic stroke subjects were recruited. The MTHFR 677 C>T and 1298A>C, ACE I/D and ApoEpolymorphisms were genotyped and the epistasis interaction were analyzed. The MTHFR 677 C>T and ApoE polymorphisms demonstrated significant associations with susceptibility to hypertension in multiple logistic regression models, multifactor dimensionality reduction and a classification and regression tree. In addition, the logistic regression model demonstrated that significant interactions between the ApoE E3E3, E2E4, E2E2 and MTHFR 677 C>T polymorphisms existed. In conclusion, the results of this epistasis study indicated significant association between the ApoE and MTHFR polymorphisms and hypertension.

Systematic review of interventions to improve the provision of information for adults with primary brain tumors and their caregivers

Background: Adults with primary brain tumors and their caregivers have significant information needs. This review assessed the effect of interventions to improve information provision for adult primary brain tumor patients and/or their caregivers. Methods: We included randomized or nonrandomized trials testing educational interventions that had outcomes of information provision, knowledge, understanding, recall, or satisfaction with the intervention, for adults diagnosed with primary brain tumors and/or their family or caregivers. PubMed, MEDLINE, EMBASE and Cochrane Reviews databases were searched for studies published between 1980 and June 2014. Results: Two randomized controlled, one non-randomized controlled, and 10 single group pre-post trials enrolled more than 411 participants. Five group, four practice/process change and four individual interventions assessed satisfaction (12 studies), knowledge (four studies) or information provision (2 studies). Nine studies reported high rates of satisfaction. Three studies showed statistically significant improvements over time in knowledge and two showed greater information was provided to intervention than control group participants, although statistical testing was not performed. Discussion: The trials assessed intermediate outcomes such as satisfaction, and only 4/13 reported on knowledge improvements. Few trials had a randomized controlled design and risk of bias was either evident or could not be assessed in most domains.

Deformation of a three-dimensional red blood cell in a stenosed micro-capillary

Red blood cells (RBCs) exhibit different types of motions and deformations when the blood flows through capillaries. Interestingly, due to the complex three-dimensional structure of the RBC membrane, RBCs show three-dimensional motions and deformations in the blood flow. These motions and deformations of the RBCs highly depend on the stiffness of the RBC membrane and on the geometrical parameters of the capillary through which blood flows. However, capillaries always do not have uniform cross sections and some capillaries have stenosed segments, where cross sectional area suddenly reduces. Further, some diseases can alter the stiffness of the RBC membrane drastically. In this study, the deformation behaviour of a single three-dimensional RBC is examined, when it moves through a stenosed capillary. A three-dimensional spring network is used to model the RBC membrane. The RBC’s inside and outside fluids are discretized into a finite number of mass points and treated by smoothed particle hydrodynamics (SPH) method. The capillary is considered as a rigid tube with a stenosed section. The deformation index, mean velocity and total energy of the RBC are analysed when it flows through the stenosed capillary. Further, motion and deformation of the RBCs with different membrane stiffness (KB) are compared when they flow through the stenosed segment of the capillary. The simulation results demonstrate the RBCs are subjected to a larger deformation when they move through the stenosed part of the capillary and the RBCs with lower KBvalues easily pass through the stenosed segment of the capillary. Further, RBCs having higher KBvalues have a lower mean velocity and it leads to slow down the overall blood flow rate

Deformation of a single red blood cell in a microvessel

Red blood cells (RBCs) are the most common type of cells in human blood and they exhibit different types of motions and deformed shapes in capillary flows. The behaviour of the RBCs should be studied in order to explain the RBC motion and deformation mechanism. This article presents a numerical simulation method for RBC deformation in microvessels. A two dimensional spring network model is used to represent the RBC membrane, where the elastic stretch/compression energy and the bending energy are considered with the constraint of constant RBC surface area. The forces acting on the RBC membrane are obtained from the principle of virtual work. The whole fluid domain is discretized into a finite number of particles using smoothed particle hydrodynamics concepts and the motions of all the particles are solved using Navier--Stokes equations. Minimum energy concepts are used to simulate the deformed shape of the RBC model. To verify the model, the motion of a single RBC is simulated in a Poiseuille flow and the characteristic parachute shape of the RBC is observed. Further simulations reveal that the RBC shows a tank treading motion when it flows in a linear shear flow.

Formation of the three-dimensional geometry of the red blood cell membrane

Red blood cells (RBCs) are nonnucleated liquid capsules, enclosed in deformable viscoelastic membranes with complex three dimensional geometrical structures. Generally, RBC membranes are highly incompressible and resistant to areal changes. However, RBC membranes show a planar shear deformation and out of plane bending deformation. The behaviour of RBCs in blood vessels is investigated using numerical models. All the characteristics of RBC membranes should be addressed to develop a more accurate and stable model. This article presents an effective methodology to model the three dimensional geometry of the RBC membrane with the aid of commercial software COMSOL Multiphysics 4.2a and Fortran programming. Initially, a mesh is generated for a sphere using the COMSOL Multiphysics software to represent the RBC membrane. The elastic energy of the membrane is considered to determine a stable membrane shape. Then, the actual biconcave shape of the membrane is obtained based on the principle of virtual work, when the total energy is minimised. The geometry of the RBC membrane could be used with meshfree particle methods to simulate motion and deformation of RBCs in micro-capillaries

Estimating the burden of disease attributable to high blood pressure in South Africa in 2000

Objectives To estimate the burden of disease attributable to high blood pressure (BP) in adults aged 30 years and older in South Africa in 2000. Design World Health Organization comparative risk assessment (CRA) methodology was followed. Mean systolic BP (SBP) estimates by age and sex were obtained from the 1998 South African Demographic and Health Survey adult data. Population-attributable fractions were calculated and applied to revised burden of disease estimates for the relevant disease categories for South Africa in 2000. Monte Carlo simulation modelling techniques were used for uncertainty analysis. Setting South Africa Subjects Adults aged 30 years and older. Outcome measures Mortality and disability-adjusted life years (DALYs) from ischaemic heart disease (IHD), stroke, hypertensive disease and other cardiovascular disease (CVD). Results High BP was estimated to have caused 46 888 deaths (95% uncertainty interval 44 878 - 48 566) or 9% (95% uncertainty interval 8.6 - 9.3%) of all deaths in South Africa in 2000, and 390 860 DALYs (95% uncertainty interval 377 955 - 402 256) or 2.4% of all DALYs (95% uncertainty interval 2.3 - 2.5%) in South Africa in 2000. Overall, 50% of stroke, 42% of IHD, 72% of hypertensive disease and 22% of other CVD burden in adult males and females (30+ years) were attributable to high BP (systolic BP ≥ 115 mmHg). Conclusions High BP contributes to a considerable burden of CVD in South Africa and results indicate that there is considerable potential for health gain from implementing BP-lowering interventions that are known to be highly costeffective.

Blood in our hearts or blood on our hands? The viscosity, vitality and validity of Aboriginal 'blood talk'

Blood metaphors abound in everyday social discourse among both Aboriginal and non-Aboriginal people. However, ‘Aboriginal blood talk’, more specifically, is located within a contradictory and contested space in terms of the meanings and values that can be attributed to it by Aboriginal and non-Aboriginal people. In the colonial context, blood talk operated as a tool of oppression for Aboriginal people via blood quantum discourses, yet today, Aboriginal people draw upon notions of blood, namely bloodlines, in articulating their identities. This paper juxtaposes contemporary Aboriginal blood talk as expressed by Aboriginal people against colonial blood talk and critically examines the ongoing political and intellectual governance regarding the validity of this talk in articulating Aboriginalities.

Polybrominated diphenyl ethers and age: analysis of pooled human blood serum from birth to over 60 years

Polybrominated diphenyl ethers (PBDEs) are considered to be a cost effective and efficient way to reduce flammability therefore reducing harm caused by fires. PBDEs are incorporated into a variety of manufactured products and are found worldwide in biological and environmental samples (e.g. Hites et al. 2004). Unlike other persistent organic pollutants there is limited data on PBDE concentrations by age and/or other population specific factors. Some studies have shown no variation in adult serum PBDE concentrations with age (e.g. Mazdai et al., 2003, Meironyte Guvenius et al., 2003) while Petreas et al. (2003) and Schecter et al. (2005) found results to be suggestive of an age trend in adult data but no statistically significant correlation was found. In addition to the data on adult concentrations there is limited data which investigates the levels of PBDEs in infants and young children. Fangström et al. (2005) showed that in seven year olds there was no difference in PBDE concentration when compared to adult concentrations. While Thomsen et al. (2002, 2005) found the concentration of PBDEs in pooled samples of blood serum from a 0-4 years age group to be higher than other age groups (4 to > 60 years). In addition, a family of four was studied in the U.S. and the concentrations were found to be greatest in the 18-month-old infant followed by the 5 year old child, then the mother and father (Fischer et al., 2006). The objectives of this study were to assess age, gender and regional trends of PBDE concentrations in a representative sample of the Australian population.

Determination of the levels of Polybrominated Diphenylethers (PBDEs) in pooled blood sera obtained from Australians aged 31-45 years

Polybrominated diphenylethers (PBDEs) are widely used as flame retardants in polymer materials, textiles, electronic boards and various other materials. Technical PBDE preparations are produced as mixtures of mainly penta-, octa- or decabrombiphenyl ethers1,2. PBDEs are structurally similar to other environmental pollutants like dioxins and PCBs, they are lipophilic and persistent compounds and are widespread in the environment. To date, no information is available on the levels of PBDEs in human serum in Australia. In 2003, more than 9000 blood samples were collected in Australia as part of the National Dioxins Program. The aim of this study was to evaluate PBDE concentrations in these samples, focusing on one age group.