4. Electronic Theses and Dissertations (ETDs) - Faculties submissions
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Item Surgical aortopulmonary shunts - a thirty-seven year experience in a South African tertiary institution(University of the Witwatersrand, Johannesburg, 2019-11) Dladla-Mukansi, Nontobeko Charity; Cilliers, Antoinette; Mammen, Vijay; Vanderdonk, KathyIntroduction: The surgical aortopulmonary shunt is a valuable palliative procedure in the management of congenital heart diseases. There is a paucity of data regarding aortopulmonary shunts in the developing world, including South Africa. Objectives: The primary objective was to describe the demographic, clinical and echocardiographic characteristics of children between ages 0 and 14 years that underwent surgical aortopulmonary shunts. The secondary objectives were to describe trends in aortopulmonary shunt designs, outcomes in terms of morbidity and mortality, progression to definitive surgery and to assess patency of shunts. Material and Methods: A retrospective clinical audit of patient files who underwent an aortopulmonary shunt between 01 January 1980 to 30 December 2016 was undertaken at Chris Hani Baragwanath Academic Hospital (CHBAH) in Soweto, Johannesburg. The study period was divided into 3 stages and for descriptive purposes as follows: 1980-1991 refers to period 1, 1992-2003 refers to period 2 and 2004-2016 refers to period 3. Results: A total of 177 aortopulmonary shunts were done over the 37-year study period. Of these 177 patients, 165 (93.2%) patient files were available. Fifty-six percent of the patients included in the study were male. The majority of patients were from the Gauteng Province (76.8%). The four most common diagnoses across the entire study period were tricuspid atresia (26.0%), pulmonary atresia with VSD (23.7%), tetralogy of Fallot (23.2%) and complex cardiac lesions (16.9%), with no particular trend in the proportion of these diagnoses presenting across this study period. There was no statistical difference between period 1 and 2 (p-value a=0,328) and between period 1 and 3 (p-value b=0,548). The total number of all surgeries done over the entire study period was 2145, of which 8.3% were aortopulmonary shunts. Period 1 had the highest percentage [35 (10.9%)] of aortopulmonary shunts compared to the total number of surgeries performed. There was a decline in the number of aortopulmonary shunts performed over the study periods 1-3. With no statistical difference across periods as shown in table 1 with p-value a and b. Of the different types of aortopulmonary shunts, most patients [157 (88.7%)] had a modified Blalock-Taussig shunt (BTS). The remainder of the shunts included 3 (1.7%) classic BTS, 12 (6.8%) central shunts and 5 (2.8%) unknown BTS. The percentage of modified BTS done increased from 80% in period 1 to 87.3% in period 2 and to 95.2% in period 3. Period 1 had the most complications (28.6%) compared to 11.4% in period 2 and 19.1% in period 3. Sepsis as a complication following surgery increased over the study period from 2.9% in period 1 to 3.8% and 7.9% in periods 2 and 3 respectively. Early mortality was 17.1%, 26.6% and 25.4% from periods 1-3 respectively. Late mortality declined from 17.0% in period 1 to 11.4% and 0% in periods 2 and 3 respectively. Only 37 (20.9%) patients were documented to have further surgery after the initial aortopulmonary shunt. Across all three study periods, no blocked shunts were documented. Conclusions: This study describes the characteristics and outcomes of aortopulmonary shunts over a 37-year period in a tertiary care resource limited low to middle income country setting. The commonest cardiac lesions for which aortopulmonary shunts are performed are tricuspid atresia, pulmonary atresia with VSD, tetralogy of Fallot and other complex cyanotic cardiac lesions. The frequency of aortopulmonary shunts compared to total surgeries has corrective surgery for these cardiac lesions. The modified BTS is the most frequently performed aortopulmonary shunt used for palliative surgery in our setting, which is a similar trend in developed countries. The morbidity and mortality in this study is higher than developed countries, with sepsis being the most common complication. Attention to infection control practises need to be emphasized peri- and post-operatively in our hospitals.Item Investigating 2-hydroxypropyl-β-cyclodextrin (HPβCD) as a novel therapeutic agent for breast cancer(University of the Witwatersrand, Johannesburg, 2019) Saha, Sourav Taru; Kaur, MandeepCancer cells have an increased need for cholesterol, which is required for cell membrane integrity. Cholesterol accumulation has been described in various malignancies including breast cancer. Cholesterol has also been known to be the precursor of estrogen and vitamin D, both of which play a key role in the histology of breast cancer. Elevated cholesterol levels have been linked to breast cancer therefore depleting cholesterol levels in cancer cells can be a viable strategy for treatment. 2-hydroxypropyl-β-cyclodextrin (HPβCD) is a cholesterol depleting compound which is a cyclic amylose oligomer composed of glucose units. It solubilizes cholesterol and is proven to be toxicologically benign in humans. This led us to hypothesise that it might deplete cholesterol from cancer cells and may prove to be a clinically useful compound. Our work provides experimental evidences to support this hypothesis. We identified the potency of HPβCD in vitro against two breast cancer cell lines: MCF7 (Estrogen positive, ER+), MDA-MB-231 [Triple negative breast cancer (TNBC)], and compared the results against two normal cell lines: MRC-5 (Normal Human Lung Fibroblasts) and HEK-293 (Human embryonic kidney) using cytotoxic, apoptosis and cholesterol based assays. HPβCD treatment reduced intracellular cholesterol resulting in significant breast cancer cell growth inhibition through apoptosis. The results hold true for both ER+ and TNBC. We have also tested HPβCD in vivo in MF-1 mice xenograft model and obtained 73.9%, 94% and 100% reduction in tumour size for late, intermediate and early stage TNBC. These data suggest that HPβCD can prevent cholesterol accumulation in breast cancer cells and is a promising anti- cancer agentItem An examination of tampon tax and how it effects the social, health and economical aspects of countries including a comparative analysis of how some countries have dealt with tampon tax(2019) Asmaljee, Sumaiyah SafiTampon tax is a colloquial term in common usage describing taxes levied on female menstrual hygiene products that are taxed as luxury goods in spite of the fact these items are considered necessities such as food and medicine, which are either exempted or taxed at 0% in some countries. Tampon tax in South Africa is the levying of value-added tax (VAT), to female menstrual hygiene products. Internationally, activists have initiated various campaigns and protests for the removal of tampon tax as it is not regarded as a luxury but rather a necessity, and South Africa has followed suit. There have been various campaigns and initiatives towards making female menstrual hygiene products more affordable and/ or accessible to the females from low-income households in South Africa. Reduction in sales tax rates, removal of goods and services tax on female menstrual hygiene products and the utilisation of the income earned from sales tax on female menstrual hygiene products are options available to negate the economic effects of tampon tax on females in their reproductive years. This paper discusses tampon tax and its effect on social, health and the economic well-being of South Africa. The paper will include comparative analyses to what is being done in some countries to alleviate the negative effects of the tampon tax. This paper will also examine the value-added tax in South Africa. Arguments in favour of and against tampon tax are also discussed.