Medicine & Health

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  • (2007) Chu, Stephanie Wai Ling
    Paclitaxel (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.

  • (2007) Green, Matthew
    AIMS 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.

  • (2007) O'Sullivan, Anthony John
    This 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.

  • (2018) Kaplan, Ruth
    Background: Public health organisations in Australia lag behind other sectors using client-facing smartphone applications (apps) to enhance service delivery. Patients are increasingly seeking smartphone-enabled health management resources. Mobile health (mHealth) systems incorporating apps may offer effective means of enabling patient-centred care. mHealth interventions can fail to translate into practice due to: design-reality gaps; real-world change outpacing research; or health service sociotechnical complexity. Pragmatic, participatory research methodologies may help meet these challenges. Tools such as the Consolidated Framework for Implementation Research (CFIR) offer structure around which investigators can build fit to context. Aim: Examine the feasibility and acceptability of a co-produced prototype mHealth intervention and model of care to manage gestational diabetes (GDM) focusing on barriers to translation into practice. Through Proof of Concept offer recommendations for future study. Methods: An mHealth system (SugaMama) was developed using lean, agile methodologies guided by Social Constructivist theory. It comprised a patient app (iPhone, Android); Bluetooth glucometer; and clinician web portal. Environmental analysis situated the study in a real-world context. The study was planned and evaluated by a Quality Improvement Collaborative (QIC) comprising patients, clinicians, health service managers and researchers. Mixed methods and an observational case study design were employed. Results: Sixteen GDM patients and seven clinicians trialled SugaMama over 44 days and found it to be technically feasible, acceptable and aligned with patient lifestyle. Technology functioned as intended. A sole critical issue related to planning for system downtime. Patients preferred supported self-management utilising SugaMama over standard care. Clinicians experienced increased control through viewing real-time patient data. For the next iteration more personalisation was requested by patients; clinicians sought improved medication management and integration with other systems. Conclusion: mHealth-enabled care is likely to support patient-clinician partnerships and extend health service reach. Utilisation of CFIR constructs and a QIC may support implementation. Critical barriers to translation into practice can arise despite an intervention being evidence-based; feasible; acceptable; and supported by sponsors, patients and clinicians in a target context.

  • (2019) Sarwat, Sidra
    Purpose: The tear film has a major role in dry eye disease, however its basic dynamics including spread, replenishment and turnover are not fully understood. This experimental study aimed to investigate the feasibility of using fluroscence of silicon quantum dots (Si-QDs) doped with transition metals such as scandium (Sc-Si-QDs), copper (Cu-Si-QDs) and zinc (Zn-Si-QDs) as a contrast agent to visualise and monitor the tear film. Methods: Sc-Si-QDs, Cu-Si-QDs and Zn-Si-QDs were synthesised in solution phase and characterised using photoluminescence (emission and excitation), absorbance and transient absorption measurements. The size distribution of Si-QDs was measured by TEM images. The fluorescence characteristics of these QDs were investigated when combined with TheraTears (a balanced electrolyte formula for dry eye therapy). An optical imaging system composed of a standard slit lamp biomicroscope combined with a high-resolution Zyla sCOMS camera, SOLIS software, optical mounts and emission filters (460 nm, 510 nm and 530 nm) was used for in vitro imaging of Si-QDs with TheraTears. The stability and intensity of fluorescence of the three different Si-QDs was measured. Cytotoxicity of the Si-QDs was assessed using cultured human corneal epithelial cells by trypan blue staining and MTT assays after 24 hours of exposure. Results: The average size of Si-QDs was 2.65 nm, which is desirable for visible photoluminescence. In vitro imaging of Sc-Si-QDs and Cu-Si-QDs indicated their stable and bright fluorescence with TheraTears. However, Sc-Si-QDs were significantly brighter compared to Cu-Si-QDs and Zn-Si-QDs, and the Zn-Si-QDs tended to clump in TheraTears. The fluorescence of the Si-QDs was detected even at a concentration of 0.01 ug/mL with a total volume of 10 uL. Cu-Si-QDs and Sc-Si-QDs were non-cytotoxic up to 16 ug/mL and Zn-Si-QDs at 8 ug/mL. Conclusions: The fluorescence of Cu-Si-QDs and Sc-Si-QDs was higher than Zn-Si-QDs and these Si-QDs were less toxic. Cu-Si-QDs and Sc-Si-QDs were safe over a wider concentration range than Zn-Si-QDs. Zn-Si-QDs and Cu-Si-QDs showed some aggregation at certain concentrations. Sc-Si-QDs are proposed as a better option for further in vivo imaging of the tear film.

  • (2019) Ogunlade, Samson
    This work focuses on the application of mathematical and statistical modeling to understand malaria infection and the corresponding immune responses in the human host in areas of high malaria exposure. In high malaria endemic areas, seasonal transmission occurs such that during the wet season, individuals are highly exposed to malaria infection but are not in the dry season. This work investigates how repeated exposures to malaria parasites contribute to parasite survival in the host during the dry season. By extending an existing mathematical model, exposure of individuals to P.falciparum infections over their lifetimes were simulated, with the models capturing the generation of partial immunity to these infections. Our model predicts that individuals with repeated exposure to malaria parasites acquire partial immunity with time and this partial immunity is not fully protective but elongates the duration of infection. Counterintuitively, the most protected individuals have the longest infections. Accordingly, I present the hypothesis that individuals with the most exposure and protection from malaria may be the ones responsible for carrying the parasites through the dry season. During the blood stage of malaria infection, when a shizont ruptures and releases merozoites, they must find and invade red blood cells (RBCs). However, it is known that the merozoites have a higher preference for infecting some cells (i.e. reticulocytes) compared to others. This work presents a probabilistic model of the invasion strategy a merozoite uses to find the “best” cell given the trade-off between longer search times and the benefit gained by the parasite. I observed that, different strategies of the parasites yield different susceptibilities of those parasites to killing. Overall, this work demonstrates the use of mathematical and statistical modeling concepts to analyse the strategies of malaria parasites survival which will help in contributing to the elimination of the malaria disease.

  • (2019) Eze, Thomas
    PURPOSE: Low vision rehabilitation improves the functional abilities of people with vision impairment but access to rehabilitation services remains low. This study aims to explore issues pertaining to the timing of low vision and rehabilitation services, from the patient’s perspective and translate patients’ preferences into practice. METHOD: A 2 phase qualitative study was designed. In the first phase, the views of people with visual impairment and who had accessed low vision services in Australia, were obtained through semi-structured telephone interviews. Contributions were audio-recorded, transcribed verbatim, and analysed thematically using NVivo software. This data was summarised. In Phase 2, focus groups were conducted, where the Phase 1 study was reported to low vision service providers and stakeholders with the purpose of developing an action plan to implement patient preferences. RESULTS: In Phase 1, 31 participants (median age 70 years, range 14-80, 18 females) were recruited. Participants had accessed two or more low vision rehabilitation services in all Australian states: low vision assessment, orientation and mobility, counselling, occupational therapy, peer support and library services. Participants judged the timing of their access to rehabilitation services as “good/ fine” and “useful” if it was early. Those who felt that they did not access rehabilitation services early enough held regrets and blamed it predominantly on lack of awareness of available services. Participants strongly preferred to receive information about low vision and rehabilitation services directly from their doctor at the time the diagnosis of their disease was made. In Phase 2, three focus groups with a total of 18 participants. Participants thought that eye care providers are not able to implement patient preferences in a busy clinic situation. All participants thought a consistent way of doing things across all stakeholders was required. CONCLUSION: Patients with visual impairment were most receptive to receiving information about rehabilitation services verbally, from their doctor, at the time of diagnosis of vision impairment. Low vision and eye care practitioners believed that patients preferences were not practicable in the ideal clinic consultations. A new approach that accommodates both patients and practitioner’s views was suggested.

  • (2017) Aggarwal, Gunjan
    Abstract Aims: Assessment of the differences in diagnostic performance and radiation dose between Adaptive Statistical Iterative Reconstruction (ASIR) and High Definition (HD) CT coronary angiography (CTCA) compared with Filtered Back Projection (FBP) and Standard Definition (SD) CTCA using invasive coronary angiography as a reference standard. Methods: Data from 2069 consecutive patients undergoing CTCA was collected over a period of 2 years. A total of 30 patients were separately enrolled if they had a significant stenosis and underwent invasive coronary angiogram within 3 months. All 30 patients were scanned in high definition and then had 5 reconstructions performed using SD0%ASIR, SD50%ASIR, SD70%ASIR, HD50%ASIR and HD70% ASIR. Results: Median and total (including CACS) angiographic radiation dose for 2069 patients was 2.1 mSv and 2.7 mSv respectively. Determinants of radiation dose on multivariate regression analysis were scan voltage, tube current, padding, scan length and heart rate. The mean difference in adjusted angiographic radiation dose using ANCOVA between the ASIR cohort (n=624, mean 2.2 mSv) and FBP (n=572, mean 2.29 mSv) was 0.09 mSv (P 0.0008). The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and Area under the curve (AUC) values using Receiver Operator Characteristic (ROC) curves on an intention to diagnose analysis were highest for the reconstruction HD with 70% ASIR at 94%, 89%, 75%, 98% and 0.93 for a >50% obstructive stenosis threshold on a per artery basis; and 88%, 88%, 64%, 97% and 0.91 for a >70% stenosis on a per artery basis; 100%, 67%, 96%, 100% and 0.83 for a >50% stenosis on a per patient basis; and 95%, 67%, 87%, 86% and 0.81 for a >70% stenosis on a per patient basis. The greatest benefit for HD with 70% ASIR was in patient subgroups of CACS>200, BMI>25 and stented arteries with AUC values of 0.93, 0.89 and 0.83 respectively. Conclusions: ASIR resulted in a lower adjusted angiographic radiation dose than FBP although the reduction of 4.2% was less than that observed in other studies due to the tube current reduction with ASIR scans being smaller in our study. HD with 70% ASIR reconstruction demonstrated the most robust diagnostic performance with higher specificity, PPV and AUC values than all other reconstructions due to a lower false positive rate. These benefits were the most pronounced in patients with a CACS>200, BMI>25 and stented arteries.

  • (2018) De Rosa, Nicholas
    Introduction: Skin disease is common in immunosuppressed solid organ transplant recipients (SOTRs) and skin cancer, in particular, is a major cause of morbidity and mortality in these patients. This study aims to determine the rates and risk factors for skin cancer in Australian heart and lung transplant recipients (HLTRs). It also aims to examine the spectrum of skin diseases encountered in HLTRs and their effect on quality of life (QOL). Methods: Ninety-four participants were recruited from the Dermatology Outpatient Clinic at St. Vincent’s Hospital Sydney between March and December 2016. Retrospective skin cancer diagnoses were obtained from medical records and participants were also examined prospectively for malignant and non-malignant skin disease. A questionnaire and the Dermatology Life Quality Index were administered to all participants. The probabilities of developing non-melanoma skin cancer (NMSC), squamous cell carcinoma (SCC), and basal cell carcinoma (BCC) were estimated using Kaplan-Meier analysis. The association of risk factors with skin cancer development were examined using the Cox proportional hazards model. The association of examined variables with DLQI score were assessed using univariate and multivariate logistic regression analysis. Results: Retrospectively, there were 801 post-transplant skin cancers in 61% of participants. At 5 and 10 years post-transplantation the probabilities were 41% and 67% for developing NMSC, 27% and 53% for developing BCC, and 33% and 62% for developing SCC, respectively. A prospective dermatological diagnosis was made in 87% of the participants over the study period. Actinic keratosis was the most common diagnosis, affecting 53% of participants, followed by skin cancer in 44% and warts in 15% of participants. Other non-malignant skin diseases were less common. Risk factors significantly associated with skin cancer included older age at transplantation, history of pre-transplant skin cancer, and history of ≥5 post-transplant skin cancers. Fitzpatrick skin type 3-6 was associated with a decreased risk of NMSC. Skin disease had a negative effect on the QOL of a minority of HLTRs. The use of tacrolimus was associated with better QOL scores on multivariate analysis. Conclusion: Australian HLTRs have high rates of skin cancer that exceed the rates reported for other SOTRs.