OpenUCT :: Browsing by Author "Mayosi, Bongani"

Browsing by Author "Mayosi, Bongani"

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Open Access
Analysis of desmoplakin in arrythmogenic right ventricular cardiomyopathy
(2010) Fish, Maryam; Mayosi, Bongani; Shaboodien, Gasnat
It has been shown that all forms of cardiomyopathy, including the dilated, hypertrophic, restrictive, and right ventricular arrhythmogenic forms, are found in African populations. Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare muscle disease characterised by fibrofatty replacement of the right ventricular myocardium, leading to electrical instability and eventual heart failure. Dilated cardiomyopathy (DCM) is a disease characterised by a reduction in ventricular wall thickness which leads to reduced contractility and impaired ventricular function. Mutations that cause ARVC have been reported in five desmosomal and three non-desmosomal genes.
Open Access
Antibiotics for the primary prevention of acute rheumatic fever: a meta-analysis
(BioMed Central Ltd, 2005) Robertson, Katharine; Volmink, Jimmy; Mayosi, Bongani
BACKGROUND:Rheumatic fever continues to put a significant burden on the health of low socio-economic populations in low and middle-income countries despite the near disappearance of the disease in the developed world over the past century. Antibiotics have long been thought of as an effective method for preventing the onset of acute rheumatic fever following a Group-A streptococcal (GAS) throat infection; however, their use has not been widely adopted in developing countries for the treatment of sore throats. We have used the tools of systematic review and meta-analysis to quantify the effectiveness of antibiotic treatment for sore throat, with symptoms suggestive of group A streptococcal (GAS) infection, for the primary prevention of acute rheumatic fever. METHODS: Trials were identified through a systematic search of titles and abstracts found in the Cochrane Central Register of Controlled Trials (Cochrane Library Issue 4, 2003), MEDLINE (1966-2003), EMBASE (1966-2003), and the reference lists of identified studies. The selection criteria included randomised or quasi-randomised controlled trials comparing the effectiveness of antibiotics versus no antibiotics for the prevention of rheumatic fever in patients presenting with a sore throat, with or without confirmation of GAS infection, and no history of rheumatic fever. RESULTS: Ten trials (n = 7665) were eligible for inclusion in this review. The methodological quality of the studies, in general, was poor. All of the included trials were conducted during the period of 1950 and 1961 and in 8 of the 10 trials the study population consisted of young adult males living on United States military bases. Fixed effects, meta-analysis revealed an overall protective effect for the use of antibiotics against acute rheumatic fever of 70% (RR = 0.32; 95% CI = 0.21-0.48). The absolute risk reduction was 1.67% with an NNT of 53. When meta-analysis was restricted to include only trials evaluating penicillin, a protective effect of 80% was found (Fixed effect RR = 0.20, 95% CI = 0.11-0.36) with an NNT of 60. The marginal cost of preventing one case of rheumatic fever by a single intramuscular injection of penicillin is approximately US$46 in South Africa. CONCLUSION: Antibiotics appear to be effective in reducing the incidence of acute rheumatic fever following an episode of suspected GAS pharyngitis. This effect may be achieved at relatively low cost if a single intramuscular penicillin injection is administered.
Open Access
Arrhythmogenic right ventricular cardiomyopathy type 6 (ARVC6): support for the locus assignment, narrowing of the critical region and mutation screening of three candidate genes
(BioMed Central Ltd, 2006) Matolweni, Luzuko; Bardien, Soraya; Rebello, George; Oppon, Ekow; Munclinger, Miroslav; Ramesar, Rajkumar; Watkins, Hugh; Mayosi, Bongani
BACKGROUND:Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heritable disorder characterized by progressive degeneration of right ventricular myocardium, arrhythmias and an increased risk of sudden death at a young age. By linkage analysis, ARVC type 6 was previously mapped to a 10.6 cM region on chromosome 10p12-p14 in a large North American kindred. To date, the genetic defect that causes ARVC6 has not been identified. METHODS: We identified a South African family of 13 members with ARVC segregating as an autosomal dominant disorder. The diagnosis of ARVC was based on international diagnostic criteria. All available family members were genotyped with microsatellite markers at six known ARVC loci, and positional candidate gene screening was performed. RESULTS: Genetic linkage and haplotype analysis provided lod scores that are highly suggestive of linkage to the ARVC6 locus on chromosome 10p12-p14, and the narrowing of the critical region to ~2.9 Mb. Two positional candidate genes (ITG8 and FRMD4A) were screened in which defects could possibly disrupt cell-cell adhesion. A non-positional candidate gene with apoptosis inducing properties, LAMR1P6 (laminin receptor 1 pseudogene 6) was also screened. Direct sequencing of DNA from affected individuals failed to detect disease-causing mutations in the exonic sequences of the three genes investigated. CONCLUSION: The narrowing of the ARVC6 critical region may facilitate progress towards the identification of the gene that is involved in ARVC. Identification of the causative genes for ARVC will contribute to the understanding of the pathogenesis and management of this poorly understood condition.
Open Access
Assessing strain in arrhythmogenic right ventricular cardiomyopathy using cine DENSE MRI
(BioMed Central Ltd, 2009) Ongori, Joash; Hendricks, Neil; Spottiswoode, Bruce; Meintjes, Ernesta; Epstein, Frederick; Mayosi, Bongani
The kinematics of the right ventricle (RV) are not well understood due to its thin wall and asymmetric geometry. Cine displacement encoding with stimulated echoes (cine DENSE), which measures intramyocardial displacement and strain, has been adapted for RV analysis with encouraging preliminary results in normal subjects. This preliminary study evaluates cine DENSE MRI for detecting decreased myocardial strain in arrhythmogenic right ventricular cardiomyopathy (ARVC). ARVC is a unique heart muscle disease affecting predominantly the RV. The pathological hallmark of fibro-fatty replacement of the myocardium may result in localised aneurysms and wall motion abnormalities, detectable by cardiac magnetic resonance imaging.
Open Access
The burden of antenatal heart disease in South Africa: a systematic review
(BioMed Central Ltd, 2012) Watkins, David; Sebitloane, Motshedisi; Engel, Mark E; Mayosi, Bongani
BACKGROUND: Maternal mortality in South Africa is rising, and heart conditions currently account for 41 per cent of indirect causes of deaths. Little is known about the burden of heart disease in pregnant South Africans. METHODS: We systematically reviewed the contemporary epidemiology and peripartum outcomes of heart disease in South African women attending antenatal care. Searches were performed in PubMed, ISI Web of Science, the EBSCO Africa-Wide database, the South African Union Catalogue, and the Current and Completed Research database (South Africa). References of included articles were also hand-searched. Studies reporting epidemiologic data on antenatal heart disease in South Africa were included. Data on morbidity and mortality were also collected. RESULTS: Seven studies were included in the systematic review. The prevalence of heart disease ranged from 123 to 943 per 100,000 deliveries, with a median prevalence of 616 per 100,000. Rheumatic valvular lesions were the commonest abnormalities, although cardiomyopathies were disproportionately high in comparison with other developing countries. Peripartum case-fatality rates were as high as 9.5 per cent in areas with limited access to care. The most frequent complications were pulmonary oedema, thromboembolism, and major bleeding with warfarin use. Perinatal mortality ranged from 8.9 to 23.8 per cent, whilst mitral lesions were associated with low birth weight. Meta-analysis could not be performed due to clinical and statistical heterogeneity of the included studies. CONCLUSION: Approximately 0.6 per cent of pregnant South Africans have pre-existing cardiac abnormalities, with rheumatic lesions being the commonest. Maternal and perinatal morbidity and mortality continue to be very high. We conclude this review by summarising limitations of the current literature and recommending standard reporting criteria for future reports.
Open Access
Clinical characteristics and initial management of patients with tuberculous pericarditis in the HIV era: the Investigation of the Management of Pericarditis in Africa (IMPI Africa) registry
(BioMed Central Ltd, 2006) Mayosi, Bongani; Wiysonge, Charles; Ntsekhe, Mpiko; Volmink, Jimmy; Gumedze, Freedom; Maartens, Gary; Aje, Akinyemi; Thomas, Baby; Thomas, Kandathil; Awotedu, Abolade; Thembela, Bongani; Mntla, Phindile; Maritz, Frans; Blackett, Kathleen; Nkouonlack,
BACKGROUND:The incidence of tuberculous pericarditis has increased in Africa as a result of the human immunodeficiency virus (HIV) epidemic. However, the effect of HIV co-infection on clinical features and prognosis in tuberculous pericarditis is not well characterised. We have used baseline data of the Investigation of the Management of Pericarditis in Africa (IMPI Africa) registry to assess the impact of HIV co-infection on clinical presentation, diagnostic evaluation, and treatment of patients with suspected tuberculous pericarditis in sub-Saharan Africa. METHODS: Consecutive adult patients in 15 hospitals in three countries in sub-Saharan Africa were recruited on commencement of treatment for tuberculous pericarditis, following informed consent. We recorded demographic, clinical, diagnostic and therapeutic information at baseline, and have used the chi-square test and analysis of variance to assess probabilities of significant differences (in these variables) between groups defined by HIV status. RESULTS: A total of 185 patients were enrolled from 01 March 2004 to 31 October 2004, 147 (79.5%) of whom had effusive, 28 (15.1%) effusive-constrictive, and 10 (5.4%) constrictive or acute dry pericarditis. Seventy-four (40%) had clinical features of HIV infection. Patients with clinical HIV disease were more likely to present with dyspnoea (odds ratio [OR] 3.2, 95% confidence interval [CI] 1.4 to 7.4, P = 0.005) and electrocardiographic features of myopericarditis (OR 2.8, 95% CI 1.1 to 6.9, P = 0.03). In addition to electrocardiographic features of myopericarditis, a positive HIV serological status was associated with greater cardiomegaly (OR 3.89, 95% CI 1.34 to 11.32, P = 0.01) and haemodynamic instability (OR 9.68, 95% CI 2.09 to 44.80, P = 0.0008). However, stage of pericardial disease at diagnosis and use of diagnostic tests were not related to clinical HIV status. Similar results were obtained for serological HIV status. Most patients were treated on clinical grounds, with microbiological evidence of tuberculosis obtained in only 13 (7.0%) patients. Adjunctive corticosteroids were used in 109 (58.9%) patients, with patients having clinical HIV disease less likely to be put on them (OR 0.37, 95% CI 0.20 to 0.68). Seven patients were on antiretroviral drugs. CONCLUSION: Patients with suspected tuberculous pericarditis and HIV infection in Africa have greater evidence of myopericarditis, dyspnoea, and haemodynamic instability. These findings, if confirmed in other studies, may suggest more intensive management of the cardiac disease is warranted in patients with HIV-associated pericardial disease.
Open Access
A cost-effectiveness tool to guide the prioritization of interventions for rheumatic fever and rheumatic heart disease control in African nations
(Public Library of Science, 2016) Watkins, David; Lubinga, Solomon J; Mayosi, Bongani; Babigumira, Joseph B
Author Summary: Rheumatic heart disease is a major cause of cardiovascular morbidity and mortality in Africa. Although there are effective medications and surgical procedures for rheumatic heart disease, they are under-used. What is more, these interventions can be expensive--even if they are feasible and effective. Unfortunately, there are currently very few economic studies on rheumatic heart disease, leaving ministries of health with little guidance on how to choose among various interventions and allocate resources to control programs. Our study describes the methods and data we used to develop a cost-effectiveness analysis tool that was intended specifically for decision-making in African countries. In our study, we also illustrate, in a hypothetical low-income African country, how the tool could be used. In our illustrative example, a prevention-oriented approach would save money in the long term, although other interventions could be cost-effective and feasible if enough financial resources were present. These findings contrast with previous studies and make a strong case that rheumatic heart disease prevention could be a high-priority intervention in Africa. We are making our tool publicly available and anticipate that ministries of health will use it as they develop or expand their rheumatic heart disease control programs.
Open Access
The effect of distance to health facility on the maintenance of INR therapeutic ranges in rheumatic heart disease patients from Cape Town
(2013) Barth, Dylan Dominic; Engel, Mark E; Mayosi, Bongani
Part A: is the research protocol which outlines the background and the process of this research. This study is a population-based observational study nested within the Groote Schuur Hospital (GSH) cohort of a global study, REMEDY which is a prospective, multicentre, hopital-based registry for rheumatic heart disease (RHD). This study made use of geographical information systems (GIS) as a tool to investigate the effect of distance on the maintenance of INR therapeutic ranges in RHD patients. Part B: elaborates on the background and highlights the importance of this research by exploring the existing theoretical and empirical literature relevant to the topic. It describes the importance of the maintenance of the INR therapeutic range and how geographical factors can influence patient adherence to medication, and how it can act as a barrier to access health care. It provides examples of how GIS has been used to investigate the effect of distance on adherence in other studies. This literature review aimed to establish whether the maintenance of therapeutic ranges in RHD patients on anticoagulant therapy is correlated with the distance travelled from patient's residence to the clinic where INR monitoring takes place. Part C: presents the entire project in a format suitable for journal submission. The background of this research project is summarised and the results are presented and discussed.
Open Access
Ethical challenges in obtaining informed consent for the genomic study of rheumatic heart disease: a qualitative study
(2016) Masiye, Francis; De Vries, Jantina; Mayosi, Bongani
INTRODUCTION: Advances in genetic and genomic research have introduced new challenges in obtaining informed consent for research in low and middle-income settings. However, there are only few studies that have explored challenges in obtaining informed consent in genetic and genomic research in Africa and none in South Africa. To start filling this gap, we conducted an empirical study to investigate the efficacy of informed consent procedures for a genomic study on Rheumatic Heart Disease (RHDGen) at the University of Cape Town in South Africa. The main aim of the study was to understand the ethical challenges in obtaining informed consent in the RHDGen study. METHODS: We used a qualitative study methodology involving in-depth interviews and participant observations. Our research participants were RHDGen cases and controls as well as research staff involved in the recruitment of RHDGen research participants. In total, we conducted 32 in-depth interviews with RHDGen research participants, 2 in-depth interviews with research staff and 57 direct observations of the consent procedures of RHDGen research participants. The in-depth interviews were conducted in English, audio-recorded and transcribed verbatim. All the data were analysed using thematic content analysis. The study was conducted in 3 sites within Cape Town, South Africa, and these sites were the Groote Schuur Hospital in Observatory, the Vanguard Community Health Centre in Bonteheuwel and the Heideveld Community in the Cape Flats.
Open Access
Genomic medicine in Africa: promise, problems and prospects
(BioMed Central Ltd, 2014) Wonkam, Ambroise; Mayosi, Bongani
Remarkable progress has been made in using genomic information to determine how genes are regulated, and how they interact with each other and with the environment to control complex biochemical functions of living organisms in health and disease [1]. This information will have major benefits for the prevention, diagnosis and management of many diseases, including communicable and genetic diseases. In Africa, where infectious diseases are highly prevalent, research on pathogen genomes has enhanced our understanding of disease transmission, virulence mechanisms and avoidance of host defenses [2]. It is anticipated that this information will enable the development of new diagnostic tests, vaccines and therapeutic agents; it is also likely to lead to new approaches for vector control, and reveal why individuals and populations vary in their susceptibility to infectious diseases [1].
Open Access
“I passed the test!” Evidence of diagnostic misconception in the recruitment of population controls for an H3Africa genomic study in Cape Town, South Africa
(BioMed Central, 2017-02-15) Masiye, Francis; Mayosi, Bongani; de Vries, Jantina
Background: Advances in genetic and genomic research have introduced challenges in obtaining informed consent for research in low and middle-income settings. However, there are only few studies that have explored challenges in obtaining informed consent in genetic and genomic research in Africa and none in South Africa. To start filling this gap, we conducted an empirical study to investigate the efficacy of informed consent procedures for an H3Africa genomic study on Rheumatic Heart Disease (RHDGen) at the University of Cape Town in South Africa. The main aim of the study was to understand ethical challenges in obtaining informed consent in the RHDGen study. Methods: We used a qualitative study methodology involving in-depth interviews and participant observations. Our study participants were RHDGen cases (patients), healthy controls and research staff involved in the recruitment of RHDGen cases and controls. In total, we conducted 32 in-depth interviews with RHDGen cases and controls, 2 in-depth interviews with research staff and 57 direct observations of the consent procedures of RHDGen cases and controls. The interviews were conducted in English, audio-recorded and transcribed verbatim. Data were analyzed using thematic content analysis. The study was conducted in 3 sites within Cape Town, South Africa. Results: Most healthy controls joined the RHDGen study in order to be screened for rheumatic heart disease (diagnostic misconception). A majority of RHDGen cases decided to join the RHDGen study because of therapeutic misconception. Conclusion: The ethical challenges that impacted on obtaining informed consent in the RHDGen study were complex. In this study, the main challenges were diagnostic misconception among RHDGen controls and therapeutic misconception among RHDGen cases.
Open Access
An immunohistochemical assessment of endomyocardial biopsy specimens from the South African arrhythmogenic right ventricular cardiomyopathy registry
(2014) Morse, Nicole; Wainwright, Helen; Mayosi, Bongani
Arrhythmogenic right ventricular cardiomyopathy / dysplasia (ARVC/D) is a genetic disease causing fibro-fatty replacement of the right ventricular myocardium, resulting in cardiac arrhythmias and sudden death. Part of the diagnostic work up for these patients includes a biopsy of the endocardium which has historically been difficult to interpret and of limited value in the early stages of disease. This study will focus on novel immunohistochemical stains of the cardiac desmosomes. These will be used to try to aid in the early diagnosis of ARVC.
Open Access
Immunological analysis of pericardial tuberculosis
(2011) Matthews, Kerryn; Wilkinson, Katalin; Wilkinson, Robert J; Mayosi, Bongani
Pericardial tuberculosis (TB) offers a relevant human model to study TB at the site of disease and to determine the effect of HIV-1 infection. 96 Patients with pericardial TB were recruited into this study, 68 of whom were HIV-1 infected. Where clinically indicated, pericardiocentesis was performed to drain pericardial fluid and blood was drawn. The data derived from the study provide novel insight into the immune response in the pericardium to TB infection. Furthermore, HIV-1 infection caused a dysregulation of the immune response.
Open Access
Investigation of the management of tuberculous pericarditis (IMPI) registry : survival and outcomes sub-study
(2012) Mubanga, Mwenya; Ntsekhe, Mpiko; Myer, Landon; Mayosi, Bongani
Includes abstract. Includes bibliographical references.
Open Access
The mitochondrial DNA T16189C polymorphism and HIV-associated cardiomyopathy: a genotype-phenotype association study
(BioMed Central Ltd, 2009) Shaboodien, Gasnat; Engel, Mark E; Syed, Faisal; Poulton, Joanna; Badri, Motasim; Mayosi, Bongani
BACKGROUND: The mitochondrial DNA (mtDNA) T16189C polymorphism, with a homopolymeric C-tract of 10-12 cytosines, is a putative genetic risk factor for idiopathic dilated cardiomyopathy in the African and British populations. We hypothesized that this variant may predispose to dilated cardiomyopathy in people who are infected with the human immunodeficiency virus (HIV). METHODS: A case-control study of 30 HIV-positive cases with dilated cardiomyopathy and 37 HIV-positive controls without dilated cardiomyopathy was conducted. The study was confined to persons of black African ancestry to minimize confounding of results by population admixture. HIV-positive patients with an echocardiographically confirmed diagnosis of dilated cardiomyopathy and HIV-positive controls with echocardiographically normal hearts were studied. Patients with secondary causes of cardiomyopathy (such as hypertension, diabetes, pregnancy, alcoholism, valvular heart disease, and opportunistic infection) were excluded from the study. DNA samples were sequenced for the mtDNA T16189C polymorphism with a homopolymeric C-tract in the forward and reverse directions on an ABI3100 sequencer. RESULTS: The cases and controls were well matched for age (median 35 years versus 34 years, P = 0.93), gender (males 60% vs 53%, P = 0.54), and stage of HIV disease (mean CD4 T cell count 260.7/muL vs. 176/muL, P = 0.21). The mtDNA T16189C variant with a homopolymeric C-tract was detected at a frequency of 26.7% (8/30) in the HIV-associated cardiomyopathy cases and 13.5% (5/37) in the HIV-positive controls. There was no significant difference between cases and controls (Odds Ratio 2.33, 95% Confidence Interval 0.67-8.06, p = 0.11). CONCLUSION: The mtDNA T16189C variant with a homopolymeric C-tract is not associated with dilated cardiomyopathy in black African people infected with HIV.
Open Access
Molecular genetics of arrhythmogenic right ventricular cardiomyopathy in South Africa
(2011) Blanckenberg, Janine; Mayosi, Bongani
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heritable disorder characterised by progressive degeneration of the right ventricular myocardium, arrhythmias and an increased risk of sudden death at a young age. Fourteen chromosomal loci have been linked to ARVC and nine disease genes have been identified. Linkage analysis of a South African family was previously performed at ARVC loci 1 to 6. ARVC loci 1 to 5 were excluded as disease loci in this family based on lack of evidence for linkage. However, a peak lod score of 2.93 was obtained for the ARVC-6 locus which is highly suggestive of linkage. Subsequently another locus (ARVC-7) and five ARVC disease genes (ARVC loci 8 to 12) have been reported. The aim of this project was to identify the disease gene that causes ARVC in this family.
Open Access
The prevalence of plakophilin-2 gene (PKP-2) mutations in South African patient with cardiomyopathy
(2008) Mbele, Mzwandile; Shaboodien, Gasna; Moolman-Smook, Hanlie; Mayosi, Bongani
Includes abstract. Includes bibliographical references (leaves 53-58).
Open Access
Quantification of echodensities in tuberculous pericardial effusion using fractal geometry: a proof of concept study
(BioMed Central Ltd, 2012) Ntsekhe, Mpiko; Mayosi, Bongani; Gumbo, Tawanda
BACKGROUND:The purpose of this study was to quantify the heterogeneous distribution of echodensities in the pericardial fluid of patients with tuberculous pericarditis using echocardiography and fractal analysis, and to determine whether there were differences in the fractal dimensions of effusive-constrictive and effusive non-constrictive disease. METHODS: We used fractal geometry to quantify the echocardiographic densities in patients who were enrolled in the Investigation of the Management of Pericarditis in Africa (IMPI Africa) Registry. Sub-costal and four chamber images were included in the analysis if a minimum of two clearly identified fibrin strands were present and the quality of the images were of a standard which allowed for accurate measurement of the fractal dimension. The fractal dimension was calculated as follows: Df=limlog N(s)/[log (l/s)], where Df is the box counting fractal dimension of the fibrin strand, s is the side length of the box and N(s) is the smallest number of boxes of side length s to cover the outline of the object being measured. We compared the fractal dimension of echocardiographic findings in patients with effusive constrictive pericarditis to effusive non-constrictive pericardial effusion using the non-parametric Mann-Whitney test. RESULTS: Of the 14 echocardiographs from 14 participants that were selected for the study, 42.8% (6/14) of images were subcostal views while 57.1% (8/14) were 4-chamber views. Eight of the patients had tuberculous effusive constrictive pericarditis while 6 had tuberculous effusive non-constrictive pericarditis. The mean fractal dimension Df was 1.325 with a standard deviation (SD) of 0.146. The measured fibrin strand dimension exceeded the topological dimension in all the images over the entire range of grid scales with a correlation coefficient (r2) greater than 0.8 in the majority. The fractal dimension of echodensities was 1.359+/-0.199 in effusive constrictive pericarditis compared to 1.330+/-0.166 in effusive non-constrictive pericarditis (p=0.595). CONCLUSIONS: The echocardiographic densities in tuberculous pericardial effusion have a fractal geometrical dimension which is similar in pure effusive and effusive constrictive disease.
Open Access
Reference intervals for the echocardiographic measurements of the right heart in children and adolescents: a systematic review
(BioMed Central Ltd, 2014) Lemmer (Hunsinger), Carolina; Engel, Mark E; Stanfliet, John; Mayosi, Bongani
BACKGROUND: Transthoracic echocardiography is the primary imaging modality for the diagnosis of right ventricular (RV) involvement in congenital and acquired heart diseases. There is increasing recognition of the contribution of RV dysfunction in heart diseases affecting children and adolescents, but there is insufficient information on reference intervals for the echocardiographic measurements of the right heart in children and adolescents that represent all the continental populations of the world.OBJECTIVE:The aim of this systematic review was to collate, from published studies, normative data for echocardiographic evaluation of the right heart in children and adolescents, and to identify gaps in knowledge in this field especially with respect to sub-Saharan Africans. METHODS: We performed a systematic literature search to identify studies of reference intervals for right heart measurements as determined by transthoracic echocardiography in healthy children and adolescents of school-going age. Articles were retrieved from electronic databases with a combination of search terms from the earliest date available until May 2013. RESULTS: Reference data were available for a broad range of variables. Fifty one studies out of 3096 publications were included. The sample sizes of the reference populations ranged from 13 to 2036 with ages varying from 5 to 21 years. We identified areas lacking sufficient reference data. These included reference data for determining right atrial size, tricuspid valve area, RV dimensions and areas, the RV % fractional area change, pulmonary artery pressure gradients and the right-sided haemodynamics, including the inferior vena cava dimensions and collapsibility. There were no data for sub-Saharan African children and adolescents. CONCLUSION: Reliable reference data are lacking for important echocardiographic measurements of the RV in children and adolescents, especially for sub-Saharan Africans.
Open Access
STK39 polymorphisms and blood pressure: an association study in British Caucasians and assessment of cis-acting influences on gene expression
(BioMed Central Ltd, 2009) Cunnington, Michael S; Kay, Chris; Avery, Peter; Mayosi, Bongani; Koref, Mauro; Keavney, Bernard
BACKGROUND:Blood pressure (BP) has significant heritability, but the genes responsible remain largely unknown. Single nucleotide polymorphisms (SNPs) at the STK39 locus were recently associated with hypertension by genome-wide association in an Amish population; in vitro data from transient transfection experiments using reporter constructs suggested that altered STK39 expression might mediate the effect. However, other large studies have not implicated STK39 in hypertension. We determined whether reported SNPs influenced STK39 expression in vivo, or were associated with BP in a large British Caucasian cohort. METHODS: 1372 members of 247 Caucasian families ascertained through a hypertensive proband were genotyped for reported risk variants in STK39 (rs6749447, rs3754777, rs35929607) using Sequenom technology. MERLIN software was used for family-based association testing. Cis-acting influences on expression were assessed in vivo using allelic expression ratios in cDNA from peripheral blood cells in 35 South African individuals heterozygous for a transcribed SNP in STK39 (rs1061471) and quantified by mass spectrometry (Sequenom). RESULTS: No significant association was seen between the SNPs tested and systolic or diastolic BP in clinic or ambulatory measurements (all p > 0.05). The tested SNPs were all associated with allelic expression differences in peripheral blood cells (p < 0.05), with the most significant association for the intronic SNP rs6749447 (P = 9.9 x 10-4). In individuals who were heterozygous for this SNP, on average the G allele showed 13% overexpression compared to the T allele. CONCLUSIONS: STK39 expression is modified by polymorphisms acting in cis and the typed SNPs are associated with allelic expression of this gene, but there is no evidence for an association with BP in a British Caucasian cohort.