Thesis (M.D.)--University of Hong Kong, 1965. / Also available in print.

Thesis (Ph. D.)--University of Texas at Austin, 2005. / Supervisor: Christopher J. McCarthy. Vita. Includes bibliographical references.

Coronary heart disease (CHD) remains one of this country's leading cause of mortality. This study has concentrated on the development of a functional biscuit, which will reduce selected risk factors for heart disease, in particular elevated serum homocysteine. The developed biscuit contains vitamins Be, Bi 2, and folic acid, all of which have been shown to be important in homocysteine metabolism. There were a number of criteria that had to be met for the author to receive the full support of Burton's Foods: (1) The biscuit must remain commercially viable and be accepted by the consumer. (2) Enzymes should not be used in the preparation of the dough. (3) The jam could not be modified in any way. Without exception, these have been successfully achieved. Jammie Dodgers were selected as the control product for a number of reasons. They are one of the UK's best selling biscuits and are consumed by both children and adults. This makes the target number of consumers very large. In addition, the standard product is high in both fat and sugar, its modification into a health promoting biscuit was therefore technically challenging. The product resulting from this project is commercially viable; it is low in fat and sugar, contains the vitamins that will deliver the full RNI on consumption of just two biscuits daily, and is not significantly different to the control product. The product is also palatable. Clinical trials have demonstrated that following consumption of the product, serum homocysteine, an independent risk factor for coronary heart disease, has been significantly reduced. In addition, there appears to be a relationship with consumption of the modified biscuit and a fall in serum lipoprotein(a). It is possible to reduce selected mutable risk factors associated with heart disease, simply by the daily consumption of a product that is liked and consumed by a great number of people. As far as the author is aware, there has been no other development of this kind prior to this study, i.e. a biscuit that will reduce the risk of coronary heart disease by lowering serum homocysteine. This biscuit is therefore the first of its kind.

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D.Phil. (Biokinetics) / Please refer to full text to view abstract

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Objective: To examine the effect of exercise-based cardiac rehabilitation program for secondary prevention of coronary heart disease on cardiac-related mortality, recurrent cardiovascular event and quality of life. Methods: All studies published between 1990 and 2013 in PubMed, and from 1980 to 2013 in EMBASE, which evaluated the effectiveness of exercise-based cardiac rehabilitation program for coronary heart disease. Using the specific keywords “Cardiac rehabilitation”, “Coronary heart disease” OR “Ischemic heart disease” [MeSH], “Exercise” OR “Physical activities” AND “Quality of life” OR “Mortality” AND Cardiovascular events” were searched. A total of 7randomized controlled trials out of 5,051articles from PubMed and 117 articles from EMBASE were included in this systematic review. The primary outcome measures used in the included seven studies were HRQOL, restenosis, cardiac event, cardiac related mortality. Similar demographic and clinical characteristics of the subjects between the intervention and the control groups were recorded. The studies were from five countries. The average age of the subjects in the seven studies was 61years, the average half of them have history of myocardial infarction. Though there were discrepancies among the results generated in the included studies, the potential benefits of exercise-based cardiac rehabilitation could be seen. Results: Compared with the non-exercise-based cardiac rehabilitation, patients allocated to the exercise-based cardiac rehabilitation program had greater improvement in HRQOL and reduction of cardiac events. The result of reducing restenosis was inconsistent. The cardiac related mortality is not significant difference between exercise-based and non-exercise-based cardiac rehabilitation. / published_or_final_version / Public Health / Master / Master of Public Health

The global burden of heart disease increases every year. It has been estimated that by the year 2020, coronary artery disease (CAD) will be the number one cause of death worldwide. Indian populations throughout the world have the highest prevalence of CAD and early onset of the disease compared to other ethnic groups. Glutathione S-transferases (GSTs) detoxify environmental agents which influence the onset and progression of disease. Dysfunctional detoxification enzymes are responsible for prolonged exposure to reactive molecules and can contribute to endothelial damage, an underlying factor in CAD. Uncoupling proteins (UCPs) 2 and 3 play an important role in the regulation of oxidative stress which contributes to chronic inflammation. Coronary artery disease is a chronic inflammatory disorder characterized by elevated levels of C-reactive protein (CRP) and pro-inflammatory cytokines such as interleukin 6 (IL-6). Polymorphisms of these genes have been linked to CAD and other chronic diseases. Statins, metabolised in the liver, are the most commonly used drug to control atherosclerosis progression in CAD patients. The pleiotropic effects of statins have been attributed to both favourable and adverse outcomes in CAD patients particularly related to myopathy and hepatotoxicity. All patients (n=102) recruited into this study were South African Indian males. A corresponding age-, gender- and ethnicity-matched control group (n=100) was also recruited. The frequency of the GSTM1 +/0, GSTP1 A105/G105, IL6 -174G/C and CRP -390C/A/T genotypes was assessed by polymerase chain reaction (PCR) and PCR restriction fragment length polymorphism (PCR-RFLP). For the in vitro study, the biological effect of atorvastatin on HepG2 cells was assessed. The metabolic activity, cytotoxicity, oxidative stress and nitric oxide production was assessed by the ATP, lactate dehydrogenase (LDH), thiobarbituric acid reactive substance (TBARS) and Griess assays, respectively. The profile of 84 microRNA (miRNA) species was evaluated using the miRNA Pathway Finder PCR SuperArray. The predicted targets of up-regulated miRNAs were determined using the online software, Targetscan. The mRNA levels of guanidinoacetoacetate (GAMT), arginine glycine aminotransferase (AGAT) and spermine oxidase (SMO) were determined using quantitative PCR. Western blotting was used to determine GAMT and phosphorylated p53 levels in treated cells. The GSTM1 0/0 and GSTP1 A105/A105 genotypes occurred at higher frequencies in CAD patients compared with the control group (36% vs. 18% and 65% vs. 48%, respectively). A significant association with CAD was observed in GSTM1 0/0 (odds ratio (OR)=2.593; 95% confidence interval (CI) 1.353 - 4.971; p=0.0043) and GSTP1 A105/A105 OR=0.6011; 95% CI 0.3803 - 0.9503; p=0.0377). We found a significant association between smoking and CAD; the presence of either of the respective genotypes together with smoking increased the CAD risk (GSTP1 A105 relative risk (RR)=1.382; 95% CI 0.958 - 1.994; p=0.0987 and GSTM1 null RR=1.725; 95% CI 1.044 - 2.851; p=0.0221). The UCP2 -866G/A and UCP3 -55C/C genotypes occurred at highest frequency in CAD patients (59% vs. 52% and 66% vs. controls: 63% respectively) and did not influence the risk of CAD. Homozygous UCP3 -55T/T genotype was associated with highest fasting glucose (11.87±3.7mmol/L vs. C/C:6.11±0.27mmol/L and C/T:6.48±0.57mmol/L, p=0.0025), HbA1c (10.05±2.57% vs. C/C:6.44±0.21% and C/T:6.76±0.35%, p=0.0006) and triglycerides (6.47±1.7mmol/Lvs. C/C:2.33±0.17mmol/L and C/T:2.06±0.25mmol/L, p<0.0001) in CAD patients. A significant association between the G allele of the IL6 -174 polymorphism and non-diabetic CAD patients was found (p=0.0431 odds ratio: 1.307, 95% CI: 1.047-1.632). A significant association with the C allele of the -390 CRP triallelic variants and CAD (p=0.021 odds ratio: 1.75, 95% CI: 1.109-2.778) was also found using a contingency of the C allele vs. the minor A and T allele frequencies. The strength of the association of the C allele with non- diabetic CAD subjects was much higher (p=0.0048 odds ratio: 2.634, 95% CI: 1.350-5.138). Circulating median levels of IL-6 (0.9 (0.90, 0.91) pg/ml and 0.9 (0.87, 0.92) pg/ml) and CRP (5.65 (1.9, 8.2) mg/l and 2.90 (1.93, 8.35) mg/l) were similar between CAD patients and controls, respectively. A similar finding was observed between controls and non-diabetic CAD subjects. Levels of IL-6 and CRP in CAD subjects were not significantly influenced by polymorphic variants of IL-6 and CRP. In the control group, the level of IL-6 was significantly influenced by the IL6 -174 G allele (p=0.0002) and the CRP -390 C allele (p=0.0416), where subjects with the homozygous GG (0.9 (0.9, 1,78) pg/ml) and CC (0.9 (0.9, 0.95) pg/ml) genotype had higher levels than the C allele carriers (0.9 (0.64, 0.91) pg/ml) or A and T carriers (0.9 (0.69, 0.91) pg/ml) combined. The lowest measure of proliferation/metabolism in HepG2 cells was observed at 20μM atorvastatin, with 82±9.8% viability. The level of cytotoxicity was increased in statin treated cells from 0.95±0.02 units to 1.11±0.03 units (p=0.001) and malondialdehyde levels was reduced from 0.133±0.003 units to 0.126±0.005 units (p=0.009) whilst nitrite levels were elevated (0.0312±0.003 units vs. control: 0.027±0.001 units, p=0.044). MicroRNAs most significantly upregulated by atorvastatin included miR-302a-3p (3.05-fold), miR-302c-3p (3.61-fold), miR-124-3p (3.90-fold) and miR-222-3p (4.4-fold); miR-19a-3p, miR-101-3p and let-7g were downregulated (3.63-fold, 2.92-fold, 2.81-fold, respectively). A list of miRNA targets identified included those with a role in metabolism and inflammation. The miR-124a specifically targets the mRNA of GAMT and SMO. / Thesis (M.Med.)-University of KwaZulu-Natal, Durban, 2012.

Thesis (Ph. D.)--University of Adelaide, 1985. / Includes bibliographical references (leaves 476-502).