Theses and Dissertations (Clinical Medicine)
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Item A radiation dose review for paediatric fluoroscopy in an Academic South African referral hospital(2017) Venter, MauritzINTRODUCTION Children are more sensitive to radiation and it is therefore important to reduce their exposure. There are currently no published data on South African paediatric fluoroscopic upper GIT, contrasted enemas and vesico-urethrogram dosage reference levels. AIM To determine the dose area product (DAP) values in common paediatric fluoroscopic examinations: Upper GIT studies, contrasted enemas and vesico-urethrograms. The primary endpoint was comparing our median and upper third quartile DAP values to international standards. METHOD We adhere to the Radiological Society of South Africa (RSSA)/South African Society of Paediatric Imaging’s (SASPI) guidelines to minimise radiation exposure. The upper third quartile and mean DAP values were collected between March 2013 and March 2016 for each study, categorised into four age groups (0–1, 2–5, 6–10 and 11–15 years) and stratified by our three major examinations. The data were compared to literature from the National UK Radiological Protection Board. RESULTS DAP values for upper GIT studies were significantly lower in the three younger age groups. There was no significant difference in the oldest age group. DAP values for vesico-urethrograms were significantly lower in the youngest age group. There was no significant difference in the three older age groups. For our contrasted enemas, there were no suitable data for comparison. CONCLUSION By following the RSSA / SASPI guidelines, our overall DAP values compared better than the UK National Patient Dose Database in the younger age groups and no worse in the older age groups.Item A descriptive retrospective record review of paediatric patients with intracardiac thrombi associated with dilated cardiomyopathy at Chris Hani Baragwanath academic hospital(2016-02-09) Morar, Deksha FayeIntracardiac thrombi associated with dilated cardiomyopathy in paediatric patients can be a source of significant morbidity and mortality. This study looked at the prevalence, risk factors and outcomes of children complicated by intracardiac thrombi, following a diagnosis of dilated cardiomyopathy at a tertiary centre. METHODS A retrospective review of all children, between the ages of 1 and 14 years, diagnosed with dilated cardiomyopathy from August 1983 to July 2011 were assessed using the paediatric cardiology database at Chris Hani Baragwanath Academic Hospital. The study population comprised of 303 children. RESULTS The prevalence of intracardiac thrombi in the children with dilated cardiomyopathy was 13.2% (40 children). The majority were located in the left ventricle (80%). The children who developed intracardiac thrombi had a lower fractional shortening compared to the group without intracardiac thrombi (p≤0.05). 20 of these children (6.6%) had evidence of embolization (15/20 to the central nervous system). 52 of the 303 children were HIV positive (17.2%). There was no statistically significant association between HIV status and the development of intracardiac thrombi (p = 0.19). The overall mortality was 8.9%. 12 of the 27 deaths occurred in the intracardiac thrombi group showing that the children with intracardiac thrombi had a poorer outcome (p≤0.05). CONCLUSION Intracardiac thrombi is a common occurrence in paediatric patients with dilated cardiomyopathy. There is a significant relationship between the development of intracardiac thrombi and a poor fractional shortening. Patients with echocardiographic evidence of intracardiac thrombi have a worse outcome.Item Acute coronary syndromes in black South African patients with human immunodeficiency virus infection(2011-10-19) Becker, Anthony CharlesBackground: South Africa is considered to be a country in epidemiologic transition with increasing rates of cardiovascular disease. In addition, it faces an HIV pandemic, with an estimated 5.5 million people infected and five hundred thousand HIV-related deaths annually. Current evidence suggests that patients infected with HIV are at a heightened risk for acute coronary syndromes (ACS) related to traditional cardiovascular risk factors, as well as factors related to the virus and its treatment (highly active anti-retroviral therapy (HAART)). HIV infection itself may independently predispose to coronary artery disease (CAD) by promoting endothelial dysfunction, a heightened pro-inflammatory state, dyslipidaemia and thrombosis, the aetiology of which is thought to be multifactoral in nature. Protease inhibitor (PI) therapy, as part of HAART, has the potential to induce an adverse metabolic phenotype, including: dyslipidaemia, insulin resistance, endothelial dysfunction and a prothrombotic state. The attributable risk of these factors in HIV-associated CAD and ACS is currently unknown, but it seems that the risk of ACS is increased by prolonged exposure to PI’s. No data currently exists on CAD in HIV patients not receiving HAART, which is problematic considering that this makes up the majority of patients in sub-Saharan Africa and that the combination of epidemiologic transition and HIV infection has the potential for greater cardiovascular morbidity, particularly with respect to atherothrombotic events. viii Aims: The aims of this thesis are twofold. Firstly, to confirm reports of epidemiologic transition in South Africa from a broad epidemiological perspective. Secondly, by focusing on treatment-naïve HIV positive black South Africans with ACS, it aims to determine differences compared to HIV negative patients with respect to demographics and risk factors, angiographic and treatment related factors as well as markers of thrombosis and inflammation with a view to providing more focused primary and secondary prevention. Methods: All the studies contained in this thesis were conducted in the Department of Cardiology, Chris Hani Baragwanath Hospital and adhere to the declaration of Helsinki. The first of the epidemiological studies, The Heart of Soweto (HOS) study (Chapter 3), was a prospectively designed registry that recorded epidemiologic data relating to the presentation, investigations and treatment of 1593 patients from Soweto with newly diagnosed cardiovascular disease during the year 2006. The second study (Chapter 4) was a cross sectional study of patients with ACS admitted to the Baragwanath coronary care unit over the year 2004 compared to the years 1975-1980. The HIV sub-study (chapters 5-8) was a prospective single centre study conducted from March 2004 to February 2008. During this time, 30 consecutive black HIV patients presenting with ACS (ACS+: HIV+ group) were enrolled. For each HIV patient with ACS, the first presenting non-HIV black patient with ACS was selected as a case control comparator (ACS+ : HIV- group). In addition, a second control group of 30 asymptomatic HIV patients, who were matched for age, sex and ethnicity (ACS- : HIV+ group), were recruited from the HIV clinic. The methodology used to compare the groups involved: clinical and demographic data collection, routine blood test evaluation, angiographic ix analysis and specific laboratory testing of various research blood parameters (including thrombotic screening and markers of inflammation and endothelial activation). Results: Chapter 3 presents the results of the large HOS study, which showed good evidence to support the theory of epidemiologic transition in Soweto. Adding to this data are the results of Chapter 4, which clearly demonstrate a substantial increase in the number of patients diagnosed with ACS at Baragwanath in recent years. Consistent with a population in epidemiologic transition, there was more than a ten-fold increase in the rate of coronary events over two decades, paralleled by increased rates of modifiable risk factors. Chapter 5 presents the clinical and angiographic data from the HIV sub-study. HIV patients with ACS were younger and had fewer traditional risk factors for CAD except for higher rates of smoking and lower HDL cholesterol levels. HIV patients had less atherosclerotic burden angiographically, but a higher thrombus burden in the infarct related arteries, suggesting a possible prothrombotic state. In addition, HIV patients had higher rates of in-stent restenosis of bare metal coronary stents at follow up. Chapters 6 and 7 present data on the thrombotic parameters between the groups, with Chapter 6 focusing mainly on coagulation pathways and Chapter 7 focusing on antiphospholipid antibodies (aPL). Chapter 8 presents data on levels of pro-inflammatory cytokines and endothelial activation markers. Greater evidence of thrombophilia was found in HIV patients with ACS as evidenced by lower Protein C (PC) levels, higher levels of Factor VIII and a higher inflammatory burden with greater degrees of endothelial cell activation - all of which increase thrombotic risk. Antiphospholipid antibodies were more prevalent in HIV patients but did not seem to be causal in the pathogenesis of thrombosis. x Conclusion: Soweto, a large, predominantly black urban area in South Africa, is in a state of epidemiologic transition, with an increasing prevalence of modifiable cardiovascular risk factors and ischaemic heart disease. Treatment-naïve HIV positive black patients presenting with ACS have different clinical and angiographic features compared to the HIV negative population. The patients are younger, more commonly male, with high rates of smoking, lower HDL levels and less atherosclerotic burden. However, there is a higher thrombotic burden, suggesting a prothrombotic state, which was evident by lower PC levels, higher factor VIII levels with a higher inflammatory burden and a greater degree of endothelial cell activation – all factors associated with a pro-atherogenic and prothrombotic state. The exact pathogenic role of HIV, independent of associated modifiable and non-modifiable risk factors, is difficult to determine, but may be important as a contributory factor in an already “vulnerable” patient. Importantly, we identified modifiable risk factors in the HIV group. Smoking may play a crucial role in the pathogenesis of ACS in these otherwise seemingly low risk patients and remains an important target for cardiovascular risk reduction. The role of HDL in the pathogenesis and prevention of HIV-associated CAD needs to be further defined, as does the role of drug eluting coronary stents in the prevention of in-stent restenosis. Cardiovascular risk assessment and appropriate primary prevention should be an important component in the management of HIV patients, regardless of treatment status. With the anticipated increase in CVD in South Africa, further research projects appropriate to the South African context will be vital in order to explore cost effective ways to provide primary and secondary prevention in order to effectively deal with the burden of epidemiological transition as well as the cardiovascular burden likely to be imposed by the HIV pandemic.Item Knowledge, attitudes and reported practices of general practitioners related to adult female patients with urinary incontinence in greater Johannesburg(2010-01-28T08:09:44Z) Padayachey, MoganambalBACKGROUND There is an extraordinary common medical condition that affects millions of people, mostly women. It is associated with high levels of disability, discomfort and loss of productivity. People seldom talk about it and suffer in silence and have a fear of being ridiculed or embarrassed. It is not breast cancer, nor osteoporosis, nor heart disease nor is it depression. It is urinary incontinence – the loss of bladder control, which affects the lives of millions of people globally. General Practitioners (GP‟s) do not have a good knowledge about the topic and are therefore not managing Urinary Incontinence (UI) appropriately. AIM To assess the knowledge, attitudes and reported practices of general practitioners related to adult female patients with urinary incontinence in Greater Johannesburg. OBJECTIVES To determine the demographics of the respondents belonging to the various Independent Practitioner Associations (IPA's). Variables include age, sex, year qualified, postgraduate qualifications, and the number of years in clinical practice. To determine the demographics of the respondents practice. Variables include, age distribution, gender distribution, and the number of patients seen with urinary incontinence per month. To determine the knowledge of the respondents regarding urinary incontinence in adult females. Variables include prevalence, aetiology, types of urinary incontinence, associated risk factors and reversible factors. v To determine the attitudes of the respondents regarding urinary incontinence in adult females. Variables include feelings of empathy, frustration, etc. To determine the management of the respondents regarding urinary incontinence in adult females. Variables include access of referral facilities, screening, examination, investigation, and medication. METHODS The study was done amongst the Independent Practitioner Associations in the greater Johannesburg area. A questionnaire was administered to GP‟s attending IPA meetings, data was collected with regards to the demographics of the GPs and their practices as well as the knowledge, attitudes and reported practices of the GPs. RESULTS The response rate cannot be calculated as the number of GPs who attended the IPA meetings is not known. One hundred and thirteen respondents met the inclusion criteria for the study. The data was collected over a 10-month period during 2006. Males accounted for 76 (68.5%) and females for 35 (31.5%) of all respondents. Two (1.8%) respondents had three postgraduate qualifications, 11 (9.7%) respondents had two postgraduate qualifications and 38 (33.6%) respondents had one postgraduate qualification. The prevalence of patients with UI was higher amongst female respondents, 33 (97.1%) as compared to male respondents 67 (88.2%). Feelings of empathy was experienced by 94 (88.7%) respondents and 81 (81%) respondents would never avoided the discussion about UI with patients. Most respondents rated their knowledge on aetiology 82 (78.1%), diagnosis 79 (73.8%), investigation 58 (54.2%) and management 58 (54.7%) as good and very good.Item The in vitro and in vivo effects of Bulbine frutescens and Bulbine natalensis on cutaneous wound healing(2010-01-27T13:28:12Z) Pather, NaliniIn recent years, there has been a growing interest in natural and traditional medicines for the treatment of wounds. Attempts to find agents that promote wound-healing and that are affordable, effective and non-toxic have a long history. In South Africa, hundreds of different indigenous plants are used to treat wounds and burns. The merits of relatively few of these have been scientifically evaluated. Bulbine natalensis and Bulbine frutescens of the Asphodelaceae family are indigenous to southern Africa and are widely used as a skin remedy. This study aimed to investigate the in vitro and in vivo effect of Bulbine natalensis and Bulbine frutescens on cutaneous wound healing. In vitro cell culture study: In vitro studies were carried out on dermal fibroblasts and human keratinocytes cultured under standard conditions using Iscove’s Modified Eagles Medium (MEM) and Dulbecco’s MEM respectively. Confluent cultures of both cell lines were treated with varying concentrations of the leaf extracts of B. frutescens and B. natalensis. These cultures were subjected to the MTT, WST-1 and BrdU assays to determine the cytotoxicity and proliferation effect of the extracts. In addition, migration of cells across a score was analysed over a 48 hour period. In vivo animal study: Excisional and incisional wounds were created on the back of 12 domestic pigs. Mirror imaged wounds were created as control wounds. The excisional wounds were biopsied at days 2, 4, 7, 10 and 16 and the incisional wounds were biopsied at day 16. The rate of closure of the wounds was also recorded. Each excisional wound was analyzed for its biochemical composition by estimating the total amount of protein, DNA, collagen and hexosamine that was present in the wound tissue. The wound healing process was documented histologically (using haematoxylin and eosin and a Mallory’s trichrome stain) and immunohistochemically (using anti- α smooth muscle actin, vascular endothelial growth factor WitsETD and transforming growth factor β receptors I and II). The incisional wounds were used to test tensile strength of the healed wounds using a tensiometer.In the in vitro studies, neither extract caused cytotoxicity to either the fibroblast or keratinocyte cells. Cell proliferation was greater than 100% at 0.1-5 and 100-300 μg/ml for Bulbine natalensis and at 0.1μg/ml for Bulbine frutescens. There was no significant difference in the effects of the two leaf extracts on cell proliferation. The biochemical analysis of the wound tissue showed a significant increase in the collagen, protein and total DNA content of both B frutescens and natalensis treated wounds when compared to the untreated wounds. There was no significant difference in the hexosamine content of both B. frutescens- and B. natalensis-treated and untreated wounds. Analysis of the wound tissue displayed an increase rate of closure of the wound tissue treated with B. frutescens and B. natalensis when compared to the untreated wounds. Full re-epithelialisation of both treated wounds occurred earlier than in the untreated wounds. These findings have important implications for the use of these extracts to treat wound healing.Item The identification of differentially expressed cell cycle -related genes in breast and colon cancer cell lines in response to chemotherapeutic drugs(2010-01-27T11:15:07Z) Rupnarain, CharleenWith the high prevalence and high mortality rate of cancer in the global community, it is increasingly essential to accelerate our understanding of the disease, to identify new genetic targets for therapy, and to pursue avenues for improving on the therapies in development and in current use. The aim of this study is to identify cell cycle-related genes whose expression is influenced by the chemotherapeutic drugs curcumin, SAHA, lycopene and thalidomide in breast and colon cancer and normal cell lines. These drugs are currently not in clinical use for cancer in South Africa, and while there have been investigative studies of these chemotherapeutic agents, this study aims to identify the specific genes that are influenced by the drugs. The result of this is that several genes that were not previously documented as targets of these drugs are highlighted. The cell cycle pathway is the area of focus as loss of regulation in the cell cycle is one of the important factors involved in promoting cancer initiation and progression. In the first instance, flow cytometry was used to identify optimal drug concentrations relative to the cell cycle stages. Following this, alterations in gene expression were assessed using a PCR-based differential display after each drug treatment. Subsequently, a more focussed approach was taken in a PCR-array analysis of panels of cell cyclerelated genes. A subset of genes is identified that is implicated in oncogenic transformation in breast cancer. This has the potential to inhibit the genetic pathways involved in breast malignancy by providing targets that perhaps may not be manipulated in current therapies. The gene expression studies here suggest that lycopene and thalidomide function in inhibiting this transformation, and play significant roles in suppressing the oncogenic state of breast cancer. Curcumin and SAHA also exhibit important functions in inhibiting tumourigenesis in colon cancer. While the results propose that the drugs have clear roles in inhibiting breast and colon cancer, they are also implicated in promoting cancer. This research has defined the genes that must be carefully monitored during drug administering as they may promote these and other cancers. The availability of these results to researchers will aid in selecting the criteria for assessing the success rate of these drugs.