Medicine & Health

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Now showing 1 - 7 of 7
  • (2011) Mittal, Rajat
    Thesis
    Introduction: Chronic wounds are costly to treat and are an increasing health problem. The aetiology of chronic wounds is multi-factorial, but recent evidence suggests that bacteria play an important role and be responsible for a majority of chronic infections. S. epidermidis and P. aeruginosa are commonly associated with chronic wounds. A major part of the virulence is their ability to form biofilms. Biofilms are a complex community of bacteria adhering to surfaces and imbedded in a biopolymer matrix that aids the bacteria in surface attachment, has water, nutrient and oxygen channels and protects the bacteria from host and antimicrobial agents. This high resistance of biofilms presents challenges to the medical community for fighting infections. Recently, topical negative pressure (TNP) dressings have been used in chronic wounds to aid healing. Although there is some research evaluating the effect of TNP dressings on biofilms, there is no research on the efficacy of a combination of TNP dressings and antiseptic instillation. Aims: Our aims were to identify the minimum eradication concentration (MEC) and the minimum biofilm eradication concentration (MBEC) of S. epidermidis and P. aeruginosa against a range of antiseptics and use sub-inhibitory concentrations of antiseptics in an in vitro wound model to assess the efficacy of TNP dressings in combination with antiseptic instillation. Method: Biofilms were generated in a biofilm generator (24 coupons at a time) with a 24 hour batch phase and a 24 hour flow-through phase. Coupons were then transferred to an in vitro wound chamber. Each wound chamber had 6 coupons. Wound chambers were subjected to various frequency of antiseptic instillation with and without TNP. 5 coupons were prepared for quantitative measurements using standard microbiological methods, while 1 coupon was prepared for scanning electron microscopy. Results: S epidermidis: MBEC of PI against S. epidermidis lay between 0.078 mg/ml and 0.156 mg/ml while the MEC was 4.883 μg/ml. The MBEC of HA against S. epidermidis was between 0.025 mg/ml and 0.05 mg/ml while the MEC was 3.125 μg/ml. Increasing frequency of antiseptic instillations without TNP resulted in a reduction in bacterial load ranging from 0.5 to 1.5 log10 reduction. Combining antiseptic instillations with TNP resulted in a greater decrease in bacterial numbers, ranging from 0.5 to almost 2.5 log10 reduction. PI instillation 12 times per day in combination with TNP was the most effective and resulted in an almost 2.5 log10 reduction in bacterial numbers. The SEM images complemented the results observed with colony counts. P aeruginosa: MBEC of PB against P. aeruginosa lay between 0.05 mg/ml and 0.20 mg/ml while the MEC was 0.2mg/ml. The MBEC of HA against P. aeruginosa was > 0.05 mg/ml while the MEC was < 3.125 μg/ml. Similar to the results observed with S. epidermidis, increasing frequency of antiseptic instillation resulted in an increased reduction in bacterial numbers. Combining TNP with PI instillation resulted in a greater decrease in bacterial numbers (7 log10 reduction) compared with PI instillation alone (5 log10 reduction). 3 times per day PB instillation resulted in approximately 0.5 log10 reduction in bacterial numbers. Addition of TNP to 3 times per day PB instillation resulted in a greater decrease in bacterial numbers (1.5 log10 reduction). Although higher frequency of PB instillation resulted in a greater decrease in bacterial load, the additive effect of TNP to PB instillation was not present. The SEM complemented these findings. Conclusion: MBEC of PI against S. epidermidis lay between 0.078 mg/ml and 0.156 mg/ml while the MEC was 4.883 μg/ml. The MBEC of HA against S. epidermidis was between 0.025 mg/ml and 0.05 mg/ml while the MEC was 3.125 μg/ml. MBEC of PB against P. aeruginosa lay between 0.05 mg/ml and 0.20 mg/ml while the MEC was 0.2mg/ml. The MBEC of HA against P. aeruginosa was > 0.05 mg/ml while the MEC was < 3.125 μg/ml. The use of TNP in combination with antiseptic instillation resulted in a greater reduction of bacterial numbers when compared with instillation alone.

  • (2016) Mirzaei, Hadis
    Thesis
    Coeliac disease (CD), also known as gluten-sensitive enteropathy, is a chronic disorder with characteristic small intestinal mucosal changes associated with nutrient malabsorption. To date, CD is still diagnosed using histology. The treatment of CD is to follow a gluten-free diet (GFD). The detection of mucosal healing in treated CD patients is important because it can determine the possibility of developing long-term manifestations of CD, such as intestinal lymphoma. According to current guidelines, duodenal biopsy is the most accurate method available for detection of mucosal healing. However, there are difficulties in early detection of healing because it may take up to three years for the biopsy to show healing. Confocal laser endomicroscopy (CLE) is a novel endoscopic method that permits on-site microscopy of the gastrointestinal mucosa. It improves the accuracy of targeted biopsies and enhances the diagnostic outcome in CD, allowing high-resolution in vivo histological analysis. Although computer-aided diagnosis (CAD) has been studied in different medical imaging techniques including computed tomography (CT), magnetic resonance imaging (MRI) and histology slides, its role has not yet been established for CLE images. Aims and methods The main goal of our first study was to design computer-based image-processing (computer-assisted-design [CAD]) techniques for use in the diagnosis of different stages of CD during endoscopy. The aim of this work was to design algorithms that could be implemented by computer software developers who need meticulous step-by-step procedures. My main contribution was to qualitatively define the characteristics of CAD images: this approach differed to previous studies which had mostly used quantitative descriptions in the diagnosis of CD in its different stages. This work is important as quantitative descriptions are non-subjective and can be used by non-experts such as computer software developers, whereas qualitative descriptions are subjective and can only be used by expert medical doctors with significant knowledge in the field. The main goal of our second study was to develop more complex criteria that can detect the severity of CD as well as detecting early signs of healing which cannot be detected using current methods of assessment. We assessed the possibility of enterocyte regeneration as the first sign of mucosal healing using confocal endomicroscopy and histology. These new features can significantly improve CD diagnostic capacity. Results Using the leave-one-out cross-validation scheme, in the first study, 80 images were used for derivative and validation cohorts. Results for our first cohort were 96% sensitivity (probability of detecting images with either villous atrophy [VA] or crypt hypertrophy [CH]) and 89% specificity (probability of detecting normal images). In the validation cohort, a new set of images was used. Due to their overall lower quality, this set of images was more challenging. Results for this cohort were 91% accuracy, 97% sensitivity, 79% specificity, 93% sensitivity and 87% specificity. In the second study, 800 CLE images were produced from 17 subjects. These images were paired with 80 forceps biopsies for analysis. The receiver operating characteristic (ROC) area, using a cut-off of ‘1’, showed the area under the curve (AUC) of 0.94 (95% confidence interval [CI]: 0.83–1.00) for CLE and 0.94 (95% CI: 0.82–1.00) for histopathology. Conclusion In conclusion, we have shown that our algorithm for the automated diagnosis of CD is highly accurate and can be incorporated into the CLE processor for real-time CD diagnosis. In our first study, we proved that CLE accurately detects the enterocyte and goblet cellular regeneration that is representative of CD treatment response. Through CLE, detailed mucosal information is provided, thus enabling endoscopists to make accurate CD diagnoses as well as instantaneously assessing the healing process in treated patients. Future directions The results of our second study can be incorporated into the already developed algorithm and increase the diagnostic capacity of CAD systems. There is also the possibility of detecting fluorescein leakage in the intestinal mucosa of CD patients. Although this leakage has been studied broadly in inflammatory bowel disease, its diagnostic role in CD has never been studied. This could be the major extension to the work reported in this thesis.

  • (2017) Veera, Jacqueline Margaret
    Thesis
    Background Accurate delineation of treatment volumes for radiotherapy is a crucial step in radiation treatment, but can be associated with considerable uncertainty and variability. Magnetic resonance imaging (MRI) has a proven benefit in the staging of cervical cancer and for image guided adaptive brachytherapy; however there is a paucity of data for the role of MRI in delineating external beam radiotherapy treatment volumes. Aims 1) Quantify the proportion of women with cervical cancer in whom there is evidence to support the use of MRI for radiotherapy planning (RTP), 2) Evaluate the effect of an educational intervention on MRI consistency of volume delineation for external beam target volumes, and 3) Assess volume delineation for external beam radiotherapy on MRI compared to the current standard of care, computer tomography (CT) imaging. Methods Data from an Australian model for estimating the optimal radiotherapy utilization rate for cervical cancer were used and a literature review was performed for each patient group to assess the evidence for the use of MRI for RTP. To evaluate the second aim contours from eleven clinicians were analysed before and after an educational intervention. For the third aim, twenty patients with locally advanced cervical cancer underwent a dedicated MR simulation with a 3T Skyra MRI following CT simulation, four clinicians independently contoured each CT and MRI dataset. The Dice Similarity Co-efficient (DSC) and Mean Average Surface Distance (MASD) was calculated for each structure. Results The use of an MRI for radiotherapy planning is supported in 49% of women overall with cervical cancer. The educational intervention resulted in an improvement in contouring the gross tumour, however a variable response for the other target volumes was observed. MRI contouring was associated with less variability between clinicians compared to CT contouring for most structures including the gross tumour, uterus and parametria. The overall target volume demonstrated a high level of contouring consistency on both CT and MRI, with a small improvement in the MASD seen for MRI contouring. Conclusion MRI simulation for external beam radiotherapy in cervical cancer reduces target volume variability compared to CT.

  • (2011) Yang, Lu
    Thesis
    It is now generally accepted that activated pancreatic stellate cells (PSCs) are the principal effector cells in pancreatic fibrosis, a characteristic histological feature of chronic pancreatitis. PSC activation is associated with loss of cytoplasmic vitamin A containing lipid droplets, expression of cytoskeletal protein alpha-smooth muscle actin (αSMA), increased proliferation, and synthesis and secretion of extracellular matrix (ECM) proteins (the latter, in turn, influence gene expression patterns of PSCs during the activation process). One of the leading causes of chronic pancreatitis is alcohol abuse and in vitro studies have established that alcohol and cytokines (known to be released during pancreatic necroinflammation) can individually activate PSCs. However, during alcohol-induced pancreatic injury, PSCs are likely to be exposed to a combination of ethanol and cytokines (rather than individual factors). Therefore, aims of this study were 1) to investigate the combined effects of ethanol and cytokines on PSCs; 2) to assess and compare gene expression profiles of PSCs cultured on matrices that mimick normal and diseased pancreas - MatrigelTM and collagen I, respectively; 3) to validate and study the influence of selected genes (e.g. transgelin) on PSC activation. Results of this study demonstrated that i) at low doses, ethanol (5mM), IL-1 (0.5pg/mL) or TNFα (10U/mL) alone have negligible effects on PSC activation. However, PSCs treated with a combination of ethanol and cytokines exhibit significantly increased activation; ii) in PSCs cultured on different matrices (MatrigelTM, collagen I and plastic) several genes are dysregulated (fold change>2, p<0.001 and q<0.25) as follows: a) PSCs on collagen I vs MatrigelTM 146 dysregulated genes (76↓, 70↑); b) PSCs on matrigel vs plastic 619 dysregulated genes (297↓, 322↑); and c) PSCs on collagen I vs plastic 432 dysregulated genes (178↓, 254↑); iii) selected genes (transgelin and lumican) are increased in PSCs cultured on fibrous ECM and are associated with PSC activation; iv) inhibition of transgelin expression in PSCs decreases cell proliferation. Thus, studies in this thesis have i) provided evidence in support of the hypothesis that PSCs can be activated synergistically by alcohol and cytokines, ii) shown that the gene expression profile of PSCs is altered by ECM components during PSC activation and; iii) identified a possible molecular target specific for PSCs in the diseased pancreas.

  • (2010) Allman, Christine Joy
    Thesis
    Background: Doxorubicin (DOX) is a highly effective treatment for haematological malignancies. Successful treatment may be marred by DOX-induced cardiomyopathy but early detection is problematic. While overt left ventricular (LV) dysfunction is irreversible, the natural history of early changes has not been characterised. Aim: The aim was to identify patients who are potentially at risk of developing DOX-induced cardiomyopathy. We defined patients to be at risk if any echocardiographic parameters of LV function significantly declined from baseline after treatment with DOX with or without clinical symptoms of heart failure (CHF). Method: Patients with haematological malignancies were studied at baseline and serially during DOX treatment with echocardiography (echo) and B-type natriuretic peptide (BNP) levels. Patients were then recalled at a mean of 3.5 years later and underwent echo to examine LV function. Conventional echo parameters, tissue Doppler imaging (TDI) and strain imaging were utilised to assess LV systolic and diastolic function. Results: No patients developed signs or symptoms of CHF. There were no significant changes in BNP levels during treatment and no significant changes in conventional echo parameters during treatment or at long term. TDI revealed a significant decline in LV systolic function during treatment that persisted at long term. TDI also detected a decline in LV diastolic function at long term where some changes in conventional echo parameters indicating a decline in diastolic function were also evident. Longitudinal strain and strain rate decreased significantly between cumulative dose levels of 200mg/m2 and 300mg/m2 of DOX during treatment. At long term, patients who had received a cumulative dose of > 300mg/m2 DOX, demonstrated a significant decline in longitudinal strain. Conclusions: There is a gradual and progressive subclinical decline in LV systolic function with increasing cumulative exposure to DOX. This subclinical LV systolic dysfunction persists at long term where subclinical LV diastolic dysfunction is also evident. TDI and strain are better in detecting the development of subclinical LV dysfunction than conventional parameters alone. The clinical impact of these findings remains to be determined.

  • (2010) White, Gregory Nicholas
    Thesis
    Aims This study aimed to demonstrate reliability and validity of the Stroke Rehabilitation Motivation Scale, a novel instrument designed to assess internal and external contributions to motivation. Many studies recognise motivation, in the everyday sense, as a factor affecting stroke rehabilitation, but there is no standard measure. There is also no agreement as to whether motivation in the post-stroke period is the same as the absence of depression, anxiety or stress; hence the need for an independent measure of motivation. Method The Stroke Rehabilitation Motivation Scale was adapted from the 28-item Sports Motivation Scale, which in turn was developed according to the intrinsic and extrinsic contributions to motivation identified by Self-Determination Theory. The resulting Stroke Rehabilitation Motivation Scale was tested in two stages. In the 28-item reliability stage, in a sample of 18 stroke patients from the stroke ward of Bankstown-Lidcombe Hospital, the scale was tested for Inter-rater reliability, scale reliability, and validity via comparison of high vs. low motivation groups according to a novel ‘motivation score’. The scale was shortened from 28-items (four per subscale) to 7 items (one per subscale) by selecting the most reliable items. The three intrinsic and extrinsic subscales were summed and averaged, and the amotivation score was subtracted from this to produce a ‘motivation score’, such that a person with a positive score had more motivation, either extrinsic or intrinsic, than they had amotivation. e.g. [ ( E + I )/2 – A ] In the 7-item reliability stage, a further 13 patients were recruited from Bankstown-Lidcombe and Liverpool Hospitals. The 7-item scale was tested for scale reliability, and for validity by comparison of high vs. low motivation groups as well as correlations between motivation score, anxiety, depression and stress, and rehabilitation outcomes. Results In both the 28-item and 7-item stages the scale demonstrated adequate to very good reliability. There was a lack of significant mean differences or correlations to demonstrate validity in either stage; this study does not represent a convincing demonstration of validity of the SRMS. However, it would appear that motivation is conceptually distinct from depression, anxiety and stress, and the scale definitely warrants further testing in a larger sample.

  • (2011) Hadi, Reema
    Thesis
    Biofilm is a colony of microorganisms that grow together in a structure which improves survival. In the healthcare setting, biofilm can form on chronic wounds and more readily in immunocompromised patients. It is also more likely to form on foreign materials placed within the human body for therapeutic reasons and on inadequately processed medical devices used for diagnostic or surgical reasons. The detection and elimination of these biofilms poses challenges for healthcare professionals and those involved in the cleaning of medical devices. Pseudomonas aeruginosa was grown on plastic coupons in the CDC bioreactor. The protein assay and the crystal violet assay were used to develop a method of detecting the efficacy of detergents to remove biofilm from these plastic coupons. Whether protein assay or crystal violet assays were used, similar results were obtained. Similar results were also obtained regardless of coupon or rod position. Results of biofilm removal were confirmed with confocal laser scanning and scanning electron microscope images obtained of the coupons. Some commercial medical device products were then tested. Zen and RMEC were selected as being representative of enzymatic cleaners and were found to be efficient cleaners. Matrix and Tween were selected as detergents, and were found to be less efficient cleaners. Two concentrations of NaOH at differing temperatures and contact time were also tested as possible standards against which industry could compare their products.. The protein assay was selected to test a range of hard surface cleaners. NaOH 0.4% at 700C for 5 mins was tested as a standard. Both 1% and 0.1% bleach (oxidising agent) were found to be efficient cleaners. Benzalkonium chloride (quaternary surfactant) was found to be a reasonable cleaner whereas acetic acid and 0.01% bleach were found to be inefficient cleaners. It is hoped that this research encourages the introduction of a standard of biofilm removal with which cleaners can comply. This would bring the cleaners industry in line with standards used to test sterilants and disinfectants.