Medicine, Dentistry & Health Sciences Collected Works - Theses
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ItemPremolar extraction and non-extraction : effects on buccal corridor widths and areas and frontal facial attractiveness(University of Melbourne, 2011)AIMS: This retrospective study was designed to compare and examine the pre-treatment and post-treatment arch widths and buccal corridor changes in subjects who had received orthodontic treatment either with or without four premolar extractions. The influence that the buccal corridor might have on the frontal facial attractiveness of these subjects was also assessed. MATERIALS AND METHODS: Pre-treatment and post-treatment casts, frontal smiling photographs and lateral cephalograms of 30 premolar extraction and 27 nonextraction patients were analysed to determine any significant differences in the arch width, anterior and posterior bucco-palatal inclinations of the teeth and buccal corridor widths and areas; both within and between the two study groups. Relationships between the buccal corridor measurements and the corresponding the arch widths and bucco-palatal inclinations of teeth were also examined. The post-treatment full-faced frontal smiling photographs of this sample were then evaluated in random order by 20 orthodontists, 20 dentists and 20 laypeople using a visual analogue scale (VAS). The ratings were analysed according to rater group, rater gender and number of years in practice for orthodontists and dentists to search for any statistically significant differences in the ratings on the basis of treatment groups, subject gender or buccal corridor widths and areas. RESULTS: There was a significant increase in the post-treatment maxillary inter-canine width seen in the extraction group but not in the non-extraction group. When measured at a constant arch depth in relation to the rugae, there was a significant increase in anterior arch width in the non-extraction group, but not in the extraction group. There were no significant differences in any of the buccal corridor widths or areas measured between extraction and nonextraction subjects. Consistent positive correlations were found between the measured buccal corridor width with reference to the last visible maxillary teeth with several pretreatment and post-treatment arch widths. There was a positive correlation between the post-treatment canine inclinations and the corresponding buccal corridor widths. Orthodontists and dentists gave higher mean overall frontal facial attractiveness scores than laypeople. There were no significant differences in the subject ratings of males and females raters. The number of years in practice did not seem to affect the way in which orthodontists were rating, but it did affect the ratings of dentists. Female subjects were consistently rated as being significantly more attractive than male subjects. There was no difference in ratings for extraction and non-extraction subject groups. The buccal corridor widths and areas did not affect frontal facial attractiveness ratings. CONCLUSIONS: There are likely to be significant differences in average upper anterior and posterior posttreatment arch widths in those treated either with or without premolar extractions. However, these arch width differences are not likely to be discernable in extraction and non-extraction subjects in relation to the buccal corridor widths and areas. Although there is a relationship between arch widths and buccal corridor widths when measured in relation to the last visible maxillary teeth, neither the choice of extraction or non-extraction treatment, nor the buccal corridor widths or areas appear to affect the frontal facial attractiveness of subjects.
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ItemA cephalometric study of class III orthodontic treatment : orthodontic camouflage vs orthognathic surgery(University of Melbourne, 2010)
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ItemEffect of different orthodontic adhesive removal techniques on sound, demineralised and remineralised enamel(University of Melbourne, 2010)
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ItemGenotypic and phenotypic studies in hyperplastic polyposis syndrome( 2010)Hyperplastic Polyposis Syndrome (HPS) is a condition associated with multiple serrated polyps and colorectal cancer (CRC) risk, and is related to a third pathway to human CRC known as “serrated neoplasia pathway”. Several genetic aberrations have been linked to HPS, including frequent BRAF and KRAS mutations and aberrant methyation known as CIMP. At least half of CRCs arising in HPS also show a CpG island methylator phenotype (CIMP). CIMP usually involves a wide panel of tumor suppressor genes including regulators of DNA mismatch repair (such as MLH1, MGMT), and negative regulators of Wnt signaling (such as WIF1). DNA methylation is one of many epigenetic factors that are important for cellular differentiation, gene regulation and genomic imprinting. The aberrant DNA methylation found in CIMP phenotype may be a consequence of dysfunctional machinery involved in establishing and maintaining normal DNA methylation. DNA methyltransferases DNMTs (DNMT1, -3A, -3B and -3L) are a family of proteins responsible for transfer of methyl groups specifically to cytosine in CpG dinucleotides of DNA. Given the role of DNMT’s in DNA methylation, we investigated the potential for interaction of genetic and epigenetic variation in DNMT genes, together with variation in BRAF and KRAS genes, in the molecular pathogenesis of HPS. A candidate gene approach identified no novel sequence variants that showed significant association with HPS. However, the T allele of rs62106244 (intron 10 of DNMT1 gene) was over-represented in cases with HPS (p<0.01), a finding deserving further study. The DNMT1, DNMT3A and DNMT3B promoters were un-methylated in all instances. Interestingly, the DNMT3L promoter showed low levels of methylation in polyps and normal colonic mucosa relative to matched disease free cells, and this may be important in expression of the gene in vivo. Expression levels of DNMT3L in polyps and normal terminal ileum tissue varied inversely with methylation may be a functionally important defect in gut. BRAF mutations were common (11 out of 21 polyps), whilst KRAS mutations were identified in 4 of 21 polyps. In addition, DNMT3L promoter hypermethylation was more often found in polyps harbouring KRAS mutations (p=0.0053). Attempts with candidate gene DNA methylation approaches were unsuccessful or unconvincing in assigning a single responsible gene responsible for HPS. We therefore applied a hypothesis-free approach by studying serrated polyps with Infinium HumanMethylation27 BeadChip Illumina® genome-wide promoter methylation. This approach identified three pathways: homedomain and basic-helix-loop transcription factors, homeobox genes and the ERK pathway, demonstrating co-ordinate methylation of genes in the polyps compared to normal controls; we speculated that the functional consequences, could explain HPS pathogenesis. This study has found that DNMT3L may be of a functional importance in gut functioning and in particular is associated with polyps harbouring KRAS mutation. A non-candidate gene approach also identified important pathways that may explain the complex aetiology of HPS.
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ItemSerological studies into the natural history of chronic hepatitis B( 2011)Chronic hepatitis B (CHB) infection represents a global health problem, with an estimated 400 million people affected worldwide. The potential long term sequelae includes cirrhosis, hepatic decompensation and hepatocellular carcinoma. The paradigm for treatment of chronic hepatitis B virus (HBV) is evolving with the advent of newer medications, improved laboratory assay sensitivity and an increased understanding of the natural history of chronic infection. The natural history of CHB is typically regarded as consisting of four phases which are classified by specific biochemical, serological and virological characteristics, including serum ALT levels, HBeAg serostatus and HBV DNA titre. Whilst serum HBsAg is the serological hallmark of HBV infection, measurement of the serum HBsAg titre is currently not required for the distinction between the different phases of CHB, and is also not routinely assessed during antiviral therapy. The first aim of this thesis was to perform a detailed cross-sectional examination of the baseline HBsAg titres in the different phases of the natural history of CHB. The cohort of patients with CHB that were evaluated included adult patients attending a tertiary centre, pregnant women and a paediatric group. This study demonstrated that median baseline HBsAg titres differed between the four phases of CHB, with higher titres in HBeAg positive compared to HBeAg negative patients. Furthermore there was an apparent “disconnect” between HBsAg titres and HBV DNA in the different phases of CHB. It was hypothesized that these findings may be due to the expression of HBsAg from integrated viral envelope sequences instead of HBsAg production off mRNA derived from the HBV cccDNA template, or due to differences in the immune regulation of viral replication during different phases of infection. The second aim of this thesis was to evaluate the changes in serum HBsAg titres during long term therapy with oral nucleos(t)ide agents (NA). HBsAg clearance and seroconversion represent the ultimate endpoint in antiviral in CHB. Although clinical trials have suggested a benefit in monitoring baseline and on-treatment serum HBsAg titres during Peg-IFN therapy in predicting virological responses, there is little data on the effect of oral NA on HBsAg titres. In this thesis, different patterns of HBsAg decline during oral NA therapy were observed, although overall the on- treatment reduction in HBsAg titres were modest in comparison to that previously described in the literature with Peg-IFN therapy. This was attributed to the indirect affect of oral NAs on HBsAg synthesis via inhibition of the intracellular cccDNA conversion pathway, with a subsequent decline in pre-existing cccDNA molecules over time. Serum anti-HBs is usually only detectable on current commercial assays once HBsAg seroclearance has occurred, and is thought to be due anti-HBs complexing into immune aggregates with the excess envelope proteins. The third aim of this thesis was to test the serum and the B-cell component of peripheral blood mononuclear cells (PBMCs) for anti-HBs in patients who also test positive for serum HBsAg. A minority of patients had detectable anti-HBs by the commercial immunoassay. It was hypothesized that there would be a higher proportion of patients with detectable anti-HBs in the B-cell component of PBMCs. Unfortunately, anti-HBs was not detected in the lysate of B-cells using two commercial immunoassays, and an in-house enzyme linked immunosorbent assay (ELISA) could not be optimised for technical reasons. In conclusion, the measurement of baseline and on-treatment HBsAg titres has the potential to become the next focus of translational and clinical research in CHB. In the context of the natural history of CHB, monitoring of baseline HBsAg titres may facilitate an improved understanding of the interplay between HBV with the innate and adaptive immune response. Finally, monitoring of HBsAg titres may allow the development of new algorithms to individualise patient therapy, and also encourage further study of novel therapeutic strategies which more directly affect HBsAg levels.