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(2007)ThesisPaclitaxel (PTX) is an effective anti-mitotic drug. It stops cancer from spreading by interfering with the microtubule dynamics which in turn leads to cell cycle arrest and eventually cell death. Despite the clinical success in treating different types of cancers, resistance to PTX remains a major hurdle for successful treatment in relapse patients. Albendazole (ABZ) is a popular anthelmintic used world-wide for the treatment of various types of helmintic infections. In helminthes, ABZ binds to β-tubulin and inhibits microtubule polymerisation. It was subsequently found that ABZ has anti-cancer activity. This study was carried out to study the effects of ABZ on PTX sensitive and PTX resistant human ovarian carcinoma cells. Cell growth assays revealed that the anti-proliferative activity of ABZ was not only effective on the PTX-sensitive human ovarian carcinoma cell line lA9, but also on its PTX-resistant sub-line, lA9PTX22. The ICso values of ABZ in lA9 and lA9PTX22 were 205 nM and 322 nM, respectively. Confocal images demonstrated that ABZ disrupted the microtubule network and caused formation of short microtubule bundles in both cell lines. Further analysis using tubulin polymerisation assay showed that the percentage of polymerised tubulin in lA9 and lA9PTX22 was increased by 58.9 % and 20.6 % respectively. Together, these results revealed for the first time that ABZ interacts with microtubules in human cancer cells and causes their polymerisation. It was also demonstrated that ABZ increased the release of cytochrome c, an important component of the intrinsic pathway in apoptosis. It was found that the expression of Bim, a BH-3 only pro-apoptotic protein was not elevated after ABZ treatment. The results presented in this study provide some information on the effect of ABZ on the microtubule network which could relate to its apoptotic effect in human ovarian carcinoma cells.
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(2007)ThesisAIMS 1. To establish the patient demographics, risk factors, causative organisms, levels of antibiotic resistance, clinical presentations and treatment patterns of keratitis at a tertiary referral hospital in Australia. 2. To establish any change in these factors over 5 years. 3. Establish the factors associated with poor outcomes. METHODS: A retrospective audit of all patients who had a corneal culture in 5 years was conducted. Patients' clinical information was gathered from medical records and smear, culture and antibiotic resistance results were gathered from the local microbiology database. Associations between risk factors for keratitis and patient variables were analysed statistically. Outcome of a patient's episode of keratitis was classified as poor using final criteria. Trends over time in variables were analysed using linear regression. RESULTS: Two hundred and fifty-three (253) corneal cultures of 231 patients were included. Sixty percent (60%) of patients were male and there was a bimodal distribution in the age of presentation. Common risk factors for keratitis were contact lens wear (22%), ocular surface disease (18%), ocular trauma (16%) and prior ocular surgery (11 %). Corneal cultures were positive in 65% of cases and Pseudomonas aeruginosa (27%), coagulase-negative staphylococci (13%), Staphylococcus aureus (12%) and fungi (7%) were recovered. There was significant variation in the monthly recovery of P. aeruginosa (p=0.04) and fungi (p=0.02) which were more frequent in summer months, while Streptococcus pneumonia (p=0.04) was more common in winter months. Antibiotic resistance of cultured bacteria to cephalothin increased significantly (2% to 12%; p=0.02). Final vision of 6/12 or better was found in 48% (100) of cases while a poor outcome was seen in 28% (58) of cases. Multivariate analysis showed that the relative risk of a patient having a poor outcome was 4.3x (confidence interval [Cl] 2.0 to 9.5) if they had severe keratitis, 4.1 x (Cl 1.8 to 9.5) if they had keratitis related to ocular surface disease and 3.8x (Cl 1.8 to 8.3) if they were over 50 years old. CONCLUSIONS 1. In this series the most common risk factor for keratitis was contact lens wear and the most commonly isolated organism was P. aeruginosa which had seasonal variation in rate of recovery. 2. Keratitis related to contact lens wear became more frequent while keratitis related to prior ocular surgery became less frequent. 3. A poor outcome is more likely in patients with severe keratitis, keratitis related to prior ocular surface disease or older age.
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(2007)ThesisThis thesis investigates professionalism in undergraduate medical students. Professionalism is comprised of values and behaviours that underpin the contract between the public and the medical profession. Medical errors are reported to result in significant morbidity and are in-part related to underdeveloped professionalism. The aim was to determine whether aspects of professionalism were underdeveloped in medical students. A questionnaire with 24 clinical and medical student vignettes was taken by Year 2, 4, and 6 medical students from UNSW Medicine 3801 and their responses where compared to responses from practicing Clinical Academics. Second, fourth and sixth Year medical students' responses differed from Academics in two aspects of professionalism, firstly, high ethical and moral standards and secondly, humanistic values such as integrity and honesty. A second component of this thesis was to determine whether student's responses to professionalism changed as they progressed through the medical program. Year 2 and 4 students had very similar responses except for the aspect responsibility and accountability. Similarly, the Year 2 and 6 students differed in only two of eight aspects of professionalism, that is, high ethical and moral standards and humanistic values and responsibility and accountability. These findings suggest that students' approaches to some aspects of professionalism do change slightly as they progress through a medical course, however there does not appear to be a clear decline or development of professionalism as a whole. Responses from the Year 2, Medicine 3801 and Medicine 3802 (new medical program) medical students were compared and no statistically different responses. This finding would indicate that professional behaviour was very similar between these two groups of students. Certain aspects of professionalism seem to be underdeveloped in medical students compared with Academics. These aspects of professionalism may need to be targeted for teaching and assessment in order that students develop as professionally responsible practitioners. In turn, students with well-developed professionalism may be less involved in medical error, and if involved they may have the personal values which can help them deal with error more honestly and effective.
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