Aldolase from human heart has been purified 128-fold to a final specific activity of 11.52 units per mg. The purification procedure employed column chromatography on phosphocellulose.

No description available.

The role of free radicals and antioxidants in human disease, particularly cardiovascular disease is an area of intensive research. Diabetes mellitus is the most common condition associated with increased oxidative stress and accelerated a therosclerosis.Increased levels of lipid peroxides and diminished antioxidant vitamin status have been reported in diabetic patients and are also implicated in the chronic complications of diabetes. The autoxidation and glycoxidation reactions of glucose are sources of free radicals in vitro and a preliminary investigation that these reactions may be a source of free radicals in vivo was undertaken in patients admitted to hospital with severe hyperglycaemia or diabetic ketoacidosis. Plasma lipid peroxides were elevated 2-7 fold above the reference range, but decreased during the recovery period in these patients. Plasma urate and ascorbate levels decreased rapidly, whilst interestingly, a-tocopherol levels / lipid ratios were preserved. The study indicated the resilient nature of the antioxidant defences in plasma, although further studies are required in order to elucidate fully the role of autoxidation and glycoxidation reactions in vivo. Insulin resistance and hyperinsulinaemia are also tightly linked with atherogenesisin type II diabetes and weight loss in obese subjects plays an important part in the reversal of insulin resistance. The safety and efficacy of two weight loss interventions - very low calorie diet (VLCD) and intensive conventional dietetic (ICD) therapy - on cardiovascular risk factors and indices of oxidative stress were investigated in obese diabetic and non-diabetic subjects. The ICD therapy produced modest weight loss in patients with established diabetes with transient improvements in diastolic blood pressure and plasma ascorbate, but with a reduction in vitamin E/ serum lipid ratios. The VLCD produced large and rapid weight loss in diabetic and non-diabetic patients with improvements in cardiovascular risk factors, lipid peroxides and vitamin E/ serum lipid ratios, which were maintained after 12 months. Plasma ascorbate concentrations were significantly lower in diabetic patients than nondiabetic patients on the VLCD, indicating that formulated diets may require higher concentrations of vitamin C for diabetic patients and this requires further investigation. The VLCD successfully reversed type II diabetes and normalized plasma lipid peroxide levels in two newly diagnosed patients.

Congenital Heart Defects (CHDs), structural heart defects that are present at birth, are prevalent in approximately 1% of live births. While, historically, the presence of such defects was associated with a heightened risk of mortality, advances in medicine have allowed nearly 85% of individuals with CHDs to live into adulthood. As such, many of these individuals are reaching reproductive age and are becoming pregnant. In order to understand the implications of pregnancy among women with CHDs, a literature review was undertaken in order to elucidate the conditions that may present to the mother, as a product of the underlying defect, as well as to discern the impact of a maternal CHD on the child. Pregnancy induces hemodynamic alterations, such as an increase in stroke volume and heart rate (and thus cardiac output), and brings about an increase in blood volume. In populations with CHD, these hemodynamic changes may induce particular risks to the mother, as her cardiac condition may obstruct her ability to cope to with the heightened stress on the heart. Moreover, given that the heart may not function in an ideal manner, a less than ideal environment is present in-utero. Women with CHD suffer from elevated cardiovascular and obstetric complications, with the risk of some cardiovascular events extending into the post-partum period. During pregnancy, approximately 11% of women with CHD will experience a cardiovascular complication; this risk is highest among those with complex forms of the defect. Arrhythmia, specifically, is the most common complication, and will occur in 4.5% of pregnancies. Heart failure is also frequent, occurring in 4% to 5% of pregnancies, with the highest risk presenting in those patients with Eisenmenger syndrome and those with cyanotic forms of CHD. Pulmonary edema and thrombolytic events are also present in this population with a higher prevalence than in a healthy pregnant population. In the 6-month period after delivery, 12% of women with CHD will experience a cardiac event, with arrhythmia and heart failure as the most common complications. Obstetric complications occur in approximately 5% of pregnancies among women with CHDs, with 11% experiencing premature labor, 8.4% experiencing post-partum hemorrhage and 5.5% experiencing pregnancy-induced hypertension. Miscarriage occurs in 15% of pregnancies, with a dose-response type relationship associated with the severity of the underlying defect, as miscarriage occurs in up to 66% of pregnancies in those with Fontan palliation. Premature rupture of membranes occurs in 3.5% of pregnancies, with half of these cases occurring to patients with transposition of the great arteries. Termination of pregnancy also occurs in 5% to 8% of pregnancies, given high risk of complications to both mother and fetus. While preeclampsia is expected to occur in approximately 2-3% of pregnancies, this risk does not exceed what occurs in a healthy population. With regard to the impact of maternal CHD on the fetus, events occurring to the fetus/neonate include preterm delivery, small for gestational age, respiratory distress syndrome, intraventricular hemorrhage, and neonatal death. Between 1.5% and 2% of pregnancies will terminate in fetal mortality. Premature birth is likely in 12% to 20% births, with of 8% of neonates born as small for gestational age. Moreover, 3.5% of children born to mothers with CHD will present with CHD, themselves. Long-term effects of maternal CHD are not well-described. Despite these complications, pregnancy among women with CHD is well-tolerated and only in very few cases of those presenting with severe defects, is pregnancy counter-indicated. However, in order to mitigate risks, pre-pregnancy counseling is recommended in all women with CHD, regardless of severity of the defect. Counseling should include an overview of the form of defect, any surgical or medicinal interventions undertaken in response to the defect, an echocardiography, an exercise stress test, among other evaluations. Monitoring of the pregnancy should continue throughout gestation and delivery should occur in a specialized care facility and the mother and fetus should be monitored by a consortium of cardiologists, obstetricians, anesthesiologists, midwives. Monitoring of the mother should extend into the post-partum period until any cardiovascular or hemodynamic pregnancy-related alterations have returned to normal.

ABSTRACT Background Sudden cardiac arrest in young athletes is a tragic event that can potentially be reduced through the implementation of a pre-participation screening program. While the absolute contents of this program are debated, consensus does exist, that should such a program be implemented, a reduction in mortality will be found. The emphasis of any pre-participation screening is found in a history and basic physical examination, with or without routine electrocardiogram testing. This is based on the understanding that 90% of sudden cardiac arrests are attributable to an underlying cardiac pathology with the majority being hypertrophic cardiomyopathy. Debate continues around the cost effectiveness of such a program but there is no doubt that in a society that is promoting an active lifestyle and with the pressure of competitive sport at most schools, there is likely to be zero tolerance for not being able to screen for potentially lethal cardiac pathology.

Introduction: The global burden of non-communicable diseases (NCDs) has long been neglected, with the omission of NCDs from the Millennium Development Goals (MDGs) bearing testament to this. The growing prevalence of chronic cardio-metabolic diseases in South Africa places huge demands on the health system. This study sought to determine the community prevalence of these cardio-metabolic diseases and associated risk factors in Chiawelo, Soweto – a township undergoing rapid urbanization in the Johannesburg Health District. Methods: The study comprised 337 participants: 124 male and 213 female. This was a community based cross sectional survey using questionnaires, anthropometric and biochemical measurement of HbA1c. Cluster sampling techniques identified eligible adult participants. Regression models were performed to identify factors associated with disease. Ethical approval to conduct the study was obtained from the University of the Witwatersrand and written informed consent was obtained from the participants. Results: The study population was black with middle to higher socio-economic status and education levels below Grade 12 mostly. The prevalence of diabetes mellitus (DM) in this study population was 14%, with many undiagnosed and those with disease poorly controlled. More than half the study population had hypertension (HPT) (58%) and most were poorly controlled. This was a markedly obese population (39%) with 54% of women having a body mass index (BMI) categorised as obese (BMI ≥ 30 kg/m2). Conclusions: The burden of chronic cardio-metabolic diseases in the Johannesburg Health District has been grossly underestimated. The prevalence of HPT and DM was high and both diseases were poorly controlled with obesity reaching epidemic proportions. Countering the burden of disease involves targeting females as a high risk priority group, engaging the community in health promotion and developing a NCD surveillance system. Clinically, it is the findings of this study to support the screening of cardio-metabolic diseases from as early as 30 years of age in males and 40 years of age in females.

No description available.

M.Sc.(Med.), Faculty of Health Sciences, University of the Witwatersrand, 2010 / The progression from compensated cardiac hypertrophy to decompensation and cardiac failure is accompanied by cardiac dilatation. As cardiac failure has a poor prognosis, it is imperative to prevent the progression to cardiac dilatation and heart failure. In this regard, an understanding of the mechanisms of cardiac dilatation is vital to guide optimal therapy to prevent heart failure. Although a number of factors have been shown to contribute to the development of cardiac dilatation, to date the role of alterations in cardiac myocyte dimensions remains unclear. Hence, the aim of the current study was to determine whether changes in cardiac myocyte dimensions contribute to the process of cardiac dilatation. Methods: Two models of cardiac dilatation in pressure-overload induced cardiac hypertrophy were assessed. One model was a natural progression model, in which 18 spontaneously hypertensive rats (SHR), were assessed at 23 months of age (an age when left ventricular hypertrophy is noted to have progressed to left ventricular decompensation, dilatation and heart failure in approximately 50% of rats). The second model, a pharmacological model, was induced in 14 month old SHR (n=9) by chronic beta-adrenoreceptor activation [0.02mg/kg isoproterenol (ISO) twice daily for 4.5 months]. Chronic beta-adrenoreceptor activation in SHR, enhances the progression from compensated left ventricular hypertrophy to left ventricular dilatation. Nine normotensive Wistar Kyoto (WKY) rats were the controls for both models. Left ventricular dilatation was defined as an increase in left ventricular radius determined at controlled filling pressures using piezo-electric transducers. The classification of rats as being in heart failure was based upon the presence of pleuropericardial effusions and / or atrial thrombi. Cardiac myocytes were isolated and dimensions determined using both light microscopy and flow cytometry. Results: Left ventricular radius was increased in SHR-Failure compared to SHR-Non-Failure (p<0.01), and in SHR-ISO compared to SHR-Control (saline administration) (p<0.01), hence confirming the presence of cardiac dilatation in both models. Although, cardiac myocyte length vi was increased in all SHR groups compared to WKY (p<0.001), no differences were observed between SHR-Failure and SHR-Non-Failure, or between SHR-ISO and SHR-Control. No differences in cell length:width ratios or in cell widths were evident between the groups. The flow cytometry data confirmed the results obtained for cardiac myocyte lengths using microscopy. Moreover, a linear correlation (r=0.46, p=0.002) between flow cytometry and microscopy cardiac myocyte lengths was observed. Importantly, no relationships were evident between left ventricular radius and cardiac myocyte length (r=0.12, p=0.42 and r=0.14, p=0.35 for microscopic and flow cytometry lengths respectively). Conclusion: The results from the present study show that although pressure-overload hypertrophy is associated with lengthening of cardiac myocytes, no further changes occur with cardiac dilatation. Hence, alterations in cardiac myocyte dimensions do not contribute to the development of cardiac dilatation in pressure-overload models.

A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, in partial fulfilment of the requirements for the degree of Master of Public Health in the field of Hospital Management OCTOBER 2014 / BACKGROUND: Gelukspan District Hospital is situated in the Ngaka Modiri Molema District in the North West Province. The majority of patients admitted in the adult medical wards of this Hospital are due to two conditions namely (a) HIV/ AIDS and (b) Cardio-metabolic diseases. The Hospital regularly analyse data related to the HIV/ AIDS patients for HIV/ AIDS conditional grant. The information related to cardio-metabolic diseases are seldom analysed by the Hospital management, although there is a belief within the Hospital that more than one thirds of the patients admitted in these two wards are due to cardio–metabolic diseases. This study was planned against this background to systematically analyse the routinely collected data from the Hospital information system. The results of the study would hopefully provide the estimation of the prevalence of these diseases at a health facility level and the cost for managing these conditions. AIM: To describe the profiles of patients admitted of cardio–metabolic diseases in the Gelukspan District Hospital in the North West Province during one year study period (from 01 April 2010 to 31 March 2011). METHODOLOGY: This was a cross-sectional study based on retrospective review of routinely collected data from the Adult Medical Wards of the Gelukspan District Hospital during the one year study period (1 April 2010 to 31 March 2011). No primary data was collected for this study. The study variables included: the number of subjects with cardio-metabolic diseases among the subjects who were admitted in the Medical wards of the Hospital during one year study period; their profiles and the type and cost of laboratory tests performed for these patients at the time of admission. Permission to conduct the research at the Hospital was obtained from the North West Department of the Health and the University of the Witwatersrand ‘Human Research Ethics Committee (Medical) before commencement of the study. RESULTS: Number of admissions in male and female medical wards for noncommunicable diseases was 558. There were almost same number of female (n= 287) and male (271) admissions. The result showed that both males and females suffer equally from cardio-metabolic diseases. The age – group 8805634J DM Moalosi vi analysis showed almost a third of the subjects were below 50 years age and another third was above 65 years of age. More than 20% of the population were pensioners representing the age distribution of the study cohort. The majority of the subjects were black (97.8%) and unemployed (98%) representing the demographics of the catchment population. The majority of the women were single (55.4%). There was no significant difference between male and female patients in terms of primary clinical diagnoses. Thirty-nine percent of the males (n=108) and 56% (163) females stayed more than 3 days (the norms of average length of stay for District hospitals. The case fatality rate was 19.5% probably high in a district hospital setting, this implies that probably these patients were not managed properly at the PHC level and or at this The laboratory tests done at the time of admission included random and fasting blood glucose, and creatinine. No HbA1C, lipogram and other renal function tests were done at the time of admission contrary to the norms and guidelines for management of cardio-metabolic diseases. The laboratory test result showed the possibility of significant comorbidity among the patients. Fourteen percent of the subject probably had nephropathy. CONCLUSION: This was the first study conducted in this Hospital to systematically evaluate management of a particular group of patients. Hopefully, this study would assist the Hospital management to improve the management of patients admitted in this Hospital.

Hypertension and heart failure are intimately related with the incidence of heart failure among hypertensive subjects between 1% and 2% per year. Structural and functional myocardial abnormalities identified in hypertensive patients contribute to the progression of myocardial dysfunction. Systolic abnormalities in hypertension begin to develop in the early stages of the disease despite normal left ventricular (LV) ejection fraction (EF) and contribute to the progressive deterioration of LV systolic performance. However, these systolic abnormalities are initially not detectable by conventional echocardiographic methods. Speckle tracking echocardiography (STE) is a sensitive quantitative technique for assessing LV function. LV twist is an important contributing factor to the systolic function of the LV in health and disease and may be a better index of systolic function than ejection fraction (EF) in hypertensive patients (HTP). The remodelling process of the left ventricle in hypertension entails a complex interplay between myocyte hypertrophy and dysfunction, with qualitative changes in the extracellular matrix contributing to progressive dysfunction. Adverse LV remodeling in HTP is associated with an imbalance in collagen degradation and may contribute to the remodelling phenotype and systolic dysfunction in hypertension. Increased matrix metalloproteinase-1 (MMP1) levels contribute to development of LV dilatation and failure with higher levels of MMP1 in the myocardium of hypertensive patients with low EF than those with normal EF. Hypertension can cause systolic dysfunction as a consequence of adverse remodelling and LV hypertrophy, but given the multitude of factors involved in LV decompensation mediated by mechanical, neurohormonal and cytokine routes, the exact mechanisms that contribute to the adverse remodelling and EF deterioration are not fully elucidated. LV twist may be a contributing factor to systolic dysfunction independent of other factors, thus, a focus on abnormalities in the cardiac mechanics of twist in the left ventricle may be helpful in understanding the pathogenesis behind the transition from compensated to decompensated heart failure. Furthermore, the changes in the extracellular matrix may account for the varying morphology, EF and LV twist in HTP. The purpose of this thesis was to 1) determine LV twist in healthy adults of different age groups (n=127), 2) evaluate LV twist changes in African HTP with low (EF<50%) and preserved EF (EF ≥ 50%) (n=82) and 3) examine the relationship between LV twist and biomarkers of collagen degradation in HTP with preserved and low EF. Parasternal short-axis images of three consecutive end-expiratory cardiac cycles at LV basal and apical levels were obtained. Apical rotation (AR) and basal rotation (BR) during ejection and instantaneous LV peak systolic twist (net twist, defined as maximal value of instantaneous AR minus BR) were measured. 127 normal subjects were divided into four age groups: 20-29 (n=34); 30-39 (n=33); 40-49 (n=29); and 50-65 (n=31) years. LV twist and markers of collagen turnover (serum concentrations of matrix metalloproteinase -1 (MMP1), tissue inhibitor of MMP1 (TIMP1) and ratio of MMP1:TIMP1) were measured in 82 hypertensive patients, 41 with EF < 50% (HTLEF) and 41 with EF ≥ 50% (HTNEF). Rigid body rotation (RBR) was defined as AR and BR occurring in the same direction. Serum biomarkers were log transformed before analysis. LV twist increased with age in normal subjects. Multivariate linear regression analysis showed age as the main predictor of net LV twist (R2=0.82, P<0.0001) in normal subjects. Net LV twist was lower in HTLEF compared with HTNEF (3.34 + 1.10 vs. 11.70 + 0.67, p < 0.0001). Of 41 HTLEF patients, 28 (68%) had normal twist pattern while 13 (32%) exhibited RBR. The subgroup with RBR showed greater LV dysfunction (EF: 27.9±5.8% vs. 35±7.5%; p=0.005) and more spherical LV geometry (p=0.0009) compared with those who had normal pattern of twist. Log TIMP1, Log MMP1 and Log MMP1:TIMP1 ratio levels were higher in HTLEF compared with HTNEF (12.32 ± 0.25 vs. 11.81 ± 0.13, p<0.0001; 9.08 ± 0.32 vs. 8.00 ± 0.18, p<0.0001; -3.25 ± 0.30 vs. -3.81 ± 0.18, p<0.0001; respectively). There was an inverse correlation between Log MMP1:TIMP1 and net LV twist after adjusting for EF (r = -0.41, p <0.0001). This study established normative data and patterns for myocardial deformation (strain and LV twist) in a normal black-African adult population across different age groups and can be used as a baseline for future studies. Age was the major determinant of increased LV twist in a normal black population. LV twist may be a compensatory mechanism to preserve EF and maintain normal systolic function with advancing age and in hypertension. LV twist varies with the degree of remodeling and systolic function in hypertension. RBR represents a novel assessment of more severe LV remodeling and LV systolic dysfunction in hypertensive patients. Alterations in collagen turnover not only accompanies more adverse remodelling but also contributes to LV twist differences observed between HTLEF and HTNEF patients. The inverse relation between LV twist and loss of myocardial collagen scaffolding suggests that integrity of the extracellular matrix may play an important role in preservation of LV twist. These findings highlight the value of LV twist as a sensitive global parameter of LV systolic myocardial performance. Longitudinal studies assessing LV twist may provide significant value in clinical practice as an early marker for risk stratification in hypertensive patients who may benefit from aggressive medical therapy to prevent LV remodelling and heart failure.