400 results for Undergraduate

  • Just prenatal testing? The science, ethics, and policy of testing for Down syndrome

    Cole, Robert (2013)

    Undergraduate thesis
    University of Otago

    Prenatal testing for Down syndrome (DS) has been available for over forty years. With the development of screening technologies, testing is now offered to all pregnant women. But is the increasing use of these tests really a good thing? Is a test for DS just another test; or is it another form of disability prevention, one with unsettling and discriminatory overtones? In this thesis I argue that whether testing is permissible or not is dependent in part on the morality of abortion. After an examination of arguments regarding fetal viability, sentience, and potential, I conclude that a fetus with DS may have less right to life than a fetus without DS, but this is dependent upon one’s perception of what constitutes ‘the good life’. That raising a child with DS may result in significant disruption to parents’ lives is an additional factor to take into account. If we hold that an abortion for social reasons is an acceptable expression of reproductive autonomy, then abortion for DS should be viewed as a morally permissible act. While prenatal testing for congenital conditions is distinct from many routine pregnancy tests, it does not follow that testing for DS should be restricted. It is conceded that prenatal testing may offend some people with DS (and their families), on the ground that DS may have considerable bearing on the development of one’s identity. But while some people take offence at the prospect of testing and abortion, it is not clear that they should; for the decision to terminate a pregnancy is a complex one, based upon many different factors. As new technologies become available, it is likely that more women will choose prenatal tests. More testing may mean that the numbers of those with DS will fall. However, this possibility should not preclude women access to testing. Pregnant women do not have a responsibility to ensure the continued prevalence of any trait or disorder, and DS is no exception. The treatment of people with disabilities has improved over recent decades, and this is something one would expect to continue. Though the number of people with DS may fall, there is increasing likelihood that social support will be more comprehensive than in the past. Ensuring that this occurs is of utmost importance. By using the controversial case of testing for DS, important issues surrounding all forms of testing in pregnancy come to light. This thesis concludes that two criteria must be met for a condition to be suitable for prenatal testing: that the condition significantly disrupts parents’ lives, and that the condition significantly limits a child’s open future. Although the existing framework may need improvement, the current practice of prenatal testing enhances reproductive autonomy. It provides information on one’s pregnancy which many women find important, and enables decision-making which is otherwise unavailable. Though not without its challenges, prenatal testing for DS is morally defensible, and should continue.

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  • The Effects of Comvita Manuka Honey on Oral Mucositis in Patients treated with Radiation Therapy to the Head and Neck

    Begley, Aubrey (2011)

    Undergraduate thesis
    University of Otago

    Mucositis is a common side effect of radiation therapy to the head and neck region and one that causes considerable discomfort for patients. Mucositis compromises patients? ability to eat, drink and talk thus affecting patient health and quality of life. Currently there is no worldwide standard for the prevention or treatment of oral mucositis; care is limited to symptom control. Honey has anti-bacterial and potential anti-inflammatory properties and three trials overseas investigated its effect on radiation-induced oral mucositis. The three trials conducted in Malaysia, Iran and Egypt found that honey did reduce the incidence of severe mucositis in head and neck patients. This New Zealand mucositis trial aimed to verify the results from the three overseas trials by comparing the effects of manuka honey with current best practice on oral mucositis in head and neck patients. This report analyses a sub-set of the patients recruited to the trial; those from the Wellington and Dunedin departments. A total of 14 patients were recruited to the trial from these departments, nine recruited to the honey arm and five to the control arm. Four honey patients withdrew from the trial due to issues with the honey application and one patient withdrew from the control arm. Honey arm patients were given manuka honey and instructed to swirl 20mL (amended to 10mL) around their oral cavity and then swallow three times a day, these patients also had access to the standard of care. The control arm patients were treated with the standard of care alone. Patient assessment involved three times weekly mucositis scoring using the TROG multi-site mucositis scoring system, weekly weight and fortnightly quality of life assessment using a 65 question form adapted from the European organisation for Research and Treatment of Cancer questionnaires (EORTC QLQ-C30 and EORTC QLQ HN35). Patients were also asked to fill in food and drug diaries to assess changes in food intake and pain medication. Results showed that manuka honey was not well tolerated by our patient cohort. Patients complained of extreme nausea and stinging sensations in the oral cavity. The honey had to be diluted to be better tolerated (1:3 with another liquid). Contradictory to previous studies, preliminary analysis showed that manuka honey did not affect the extent of oral mucositis in the small cohort of New Zealand head and neck patients when taken in addition to current best practice.

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  • Effects of Orf Virus on the Inflammation Signalling Pathways of the Toll-­like, Interleukin-­1 and Tumor Necrosis Factor Receptor Families

    Turner, Ethan (2011)

    Undergraduate thesis
    University of Otago

    Poxviruses are complex, large double stranded DNA viruses that replicate in the cytoplasm of infected cells. The early phase of infection involves a two step uncoating process, firstly releasing viral core structures, then later viral DNA into the host cell before completion of their replicative lifecycle. Orf virus is the type species of the parapoxvirus genus, which infects primarily sheep and goats in addition to humans by zoonosis transmission. Resulting symptoms are characterised by rapidly developing acute pustular lesions. Orf virus is known to encode several immuno-modulatory factors to permit its replication in the presence of strong host innate and inflammatory responses. Genomic sequencing and bioinformatics analysis have identified an orf virus gene (057) encoding a structural protein containing a phosphatase motif, with close homology to vaccinia virus VH1. As structural proteins, both 057 and VH1 are predicted to become immediately available in the host cytoplasm soon after virion uncoating, where targeted dephosphorylation of intracellular signalling pathways can ensue. This study set out to investigate the potential effect of an orf viral phosphatase on cell signalling pathways through central transcription factor NFĸB, a key upregulator of pro-inflammatory cytokine and chemokine genes. Several classes of receptors, notably, toll-like receptor 4, interleukin-1 and tumor necrosis factor receptor families strongly induce NFĸB by virtue of adapter proteins which transduce signals mediated via phosphorylation and ubiquitylation events. These pathways converge on the IKK complex, which in turn phosphorylates IĸB-α, an inhibitory protein that sequesters NFĸB-p65, resulting in ubiquityn-proteasomal targeted degradation of IĸB-α effectively liberating NFĸB-p65 to undergo nuclear translocation. Assays were performed in HeLa cells to establish stimulatory dynamics and kinetics of NFĸB-p65 activation through induction with respective ligands, LPS, IL-1β, and TNF-α of the aforementioned receptors. Lysates were prepared, resolved by SDS-page and western blot analysis to determine endogenous levels of IĸB-α, and in addition to phosphorylated levels of NFĸB-p65. Initial results from preliminary assays showed rapid phosphorylation kinetics of NFĸB-p65 observable within 10 minutes following induction. The effects upon infection of cells with orf virus were then examined. The most notable result revealed an apparent temporal delay in the maximal levels of phosphorylated NFĸB-p65 induced by LPS and TNF-α when comparing mock and orf virus infected cells with a shift in the accumulation time of maximal levels of phosphorylated NFĸB-p65. Although definitive results of the involvement of orf structural protein 057 in this observation remain inconclusive at this stage, this effect could potentially be attributed to an orf virion-associated phosphatase due to the occurrence preceding viral de novo protein synthesis which is known to begin approximately 4 hours post infection.

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  • Neutrophil Activation in Inflammatory Bowel Disease

    Hoskin, Teagan Susan (2011)

    Undergraduate thesis
    University of Otago

    Abstract Inflammatory Bowel Disease (IBD) is an inflammatory condition in which neutrophils play an important role. Colonoscopy with biopsy is thought to be the best method for evaluating inflammation location, extent, and severity. However, the invasiveness of endoscopic examinations represents a strong limitation to their frequent use. Various studies have described faecal markers as powerful biomarkers of inflammation of the intestinal mucosa in patients with IBD. This thesis details the use of calprotectin and myeloperoxidase (MPO) as biomarkers of disease severity in patients with IBD, and aims to assess whether MPO is a superior biomarker to calprotectin. Abundant levels of both calprotectin and MPO are found in neutrophils. A total of 500 patients were recruited into the evaluation of Novel Biomarkers in Inflammatory Bowel Disease project cohort. However, only 100 of the initial stool samples from patients with or without IBD were used for this research. The samples had been stored at -80°C for up to one year. A short extraction procedure using 100 mg of faeces and approximately 4.9 mL of the appropriate extraction buffer was carried out. Levels of calprotectin and MPO protein were then measured by sandwich enzyme-linked immunosorbent assay (ELISA). The peroxidase activity of MPO was also measured using 3,3’,5,5’-tetramethylbenzidine (TMB) as a reducing substrate. TMB forms a blue product when it reacts with peroxidase enzymes such as MPO. The resulting colour change was read on a microplate reader at a wavelength of 630 nm. Levels of calprotectin, MPO protein, and MPO TMB activity were significantly higher in IBD patients compared to controls. There were significant correlations between calprotectin, MPO protein and MPO TMB activity (p < 0.001). Levels of calprotectin and MPO protein correlated significantly with endoscopic disease severity in patients with CD (r = 0.487, p = 0.001, n = 41, r = 0.483, p = 0.001, n = 41, respectively) and UC (r = 0.677, p << 0.001, n = 35, r = 0.552, p < 0.001, n = 35, respectively). Consequently, both calprotectin and MPO protein were able to discriminate between IBD patients with inactive and high disease severity. However, MPO TMB activity failed to correlate with disease severity in CD and UC patients (r = 0.303, p = 0.054, n = 41; r = 0.258, p = 0.134, n = 35, respectively). The results obtained from this research show that calprotectin and MPO protein correlate strongly with each other. There was also a strong correlation between MPO protein and disease severity, and MPO could successfully distinguish between inactive and high disease severity in CD and UC patients. This suggests that MPO may be useful in the diagnosis and follow-up of patients with IBD. Although, the relationships between MPO TMB activity and disease severity in patients with CD and UC were not significant results were still very promising. This assay could prove to be a faster and more cost effective approach to aid in the diagnosis and follow up of patients with IBD in the future. However, further development and optimisation of the MPO ELISA and MPO TMB assay is required to validate the results from this research.

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  • Anti-Müllerian hormone: A missing link in prostate cancer?

    Masterton, Sarah Lorraine (2011)

    Undergraduate thesis
    University of Otago

    Prostate cancer is the most frequently diagnosed cancer in men in many countries including the USA, France, Germany and New Zealand (Health, 2002, Jemal et al., 2008, Ferlay et al., 2010). The growth of human prostate tissue and the development of prostate cancer is an intricate process maintained by the fine balance of a variety of factors including androgens, estrogens, stromal-epithelial interactions, nervous system input and growth factors (Massague, 1987, Moses et al., 1990, Ittman and Mansukhani, 1997, McVary et al., 1998, Giri et al., 1999, Khandwala et al., 2000, Renehan et al., 2004). Anti-Müllerian hormone (AMH) is one growth factor that may be involved in prostate cancer progression. Previously Segev et al. (2002) showed that AMH inhibits the growth of prostate cancer cells, and Loo et al. (2008) and Segev et al. (2002) showed that its type II receptor (AMHRII) was expressed by the prostate in mice and humans, respectively. Consequently, this project sought to begin to investigate the role of AMH in prostate cancer by examining the localisation and quantifying the expression of AMH propeptide, AMH and AMHRII in benign tissue, low-grade and high-grade cancer of the human prostate using human prostate tissue samples and cells. Immunohistochemistry was used to determine the localisation of AMH propeptide, AMH and AMHRII in human prostate tissue samples, which included various disease states. Double immunofluorescence was then carried out to confirm the location of AMH and AMHRII in human prostate tissue samples. Assessment of immunoreactivity and Western blot analysis were used to quantify the expression of AMH propeptide, AMH and AMHRII expression in human prostate tissue samples. The localisation and expression of AMH and AMHRII in normal and malignant stromal and epithelial human prostate cells was also determined using immunocytochemistry, Western blot analysis and assessment of immunoreactivity, respectively. The results of this project show that AMH propeptide, AMH and AMHRII are located in human prostate stroma and epithelium at all stages of disease. Immunohistochemistry and double immunofluorescence of human prostate tissue samples (which included benign tissue, low-grade cancer and high-grade cancer) exhibited AMH propeptide, AMH and AMHRII immunoreactivity of stroma and epithelium. Immunocytochemistry of normal and malignant stromal and epithelial human prostate cells also demonstrated AMH and AMHRII immunoreactivity. Furthermore, Western blot analysis of benign and malignant human prostate tissue samples and cells revealed immunoreactive bands that may correspond to cleaved and uncleaved forms of AMH and AMHRII. This project also found that there was no significant difference in expression of AMH propeptide or AMHRII in the stroma and epithelium of benign and malignant human prostate tissue samples, as indicated by assessment of immunoreactivity and Western blot analysis. However, there was evidence to suggest that AMH expression is increased in malignancy because AMH immunoreactivity was significantly increased in the epithelium of low-grade and high-grade human prostate tissue samples. Therefore, it seems that AMH may be involved in an autocrine/paracrine growth regulatory mechanism in the human prostate, as has been demonstrated in the human testes (Racine et al., 1998), brain motor neurons (Wang et al., 2005a), and female endometrium (Wang et al., 2009a). This implies AMH may function as a growth-inhibitor (as was indicated by Segev et al.'s (2002) findings on the effect of AMH on prostate cancer cells) or as a growth-stimulator depending on the cellular context. However, further research is needed to confirm the expression pattern of AMH and AMHRII in human prostate cancer progression, and to investigate the effect of AMH peptide on normal and malignant human prostate cell growth both in vivo and in vitro.

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  • The Cost Effectiveness of Implantable Cardioverter Defibrillator Therapy in New Zealand

    De Silva, Praveen Handunnethi (2012)

    Undergraduate thesis
    University of Otago

    The Implanted Cardioverter Defibrillator (ICD) has emerged as one of the strongest therapeutic options for patients at high risk of SCD [65-67]. Despite this its high cost, in relation to other therapies, has made its use controversial in many patient groups. The repercussions are particularly visible in smaller countries like New Zealand where limited resources and doubts on cost effectiveness have resulted in lower implantation rates. The aims of this Thesis were to provide an estimation of ICD cost effectiveness in a New Zealand context and label the strongest and weakest influencers of cost effectiveness. ICD costs and efficacy data, for Secondary prevention patients and Primary prevention patient with LV dysfunction, were collected through a review of international literature and analysis of New Zealand data collected from 2000-2007. These were then entered into a computer model and run over a twenty year lifetime. Model inputs included the efficacy of an ICD in secondary and primary prevention, measured through Life Years Gained, implant mortality, the cost of an ICD, costs of adverse events, lead/battery replacement costs and cost of annual follow up. Results showed the average cost effectiveness of an ICD was NZ $107,191/ LYG, when used in secondary prevention and $178,291/ LYG in primary prevention. The overall range of cost effectiveness across all model inputs was $85,799/ LYG to $207,301/LYG. The strongest factors influencing cost effectiveness were efficacy of the device in both groups, the cost of battery replacements, longevity of ICD leads, mortality rate of primary prevention patients and the annual cost of follow up. The weakest influencers of cost effectiveness included the costs of initial ICD and implant procedure and the cost of adverse events occurring from ICDs. These findings correlated well with previous studies conducted overseas. New Zealand showed a similar range of cost effectiveness, when compared to international trials. Our estimate remained outside the range of cost effectiveness thresholds considered economically attractive however when assessed alongside other therapies was comparative to renal dialysis for end stage disease. The results of this thesis encourage an increase in implantation rates to match other Westernised countries and detail areas that need to be addressed to further improve cost effectiveness.

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  • The clinical anatomy of the chorda tympani: a micro-CT study

    McManus, Lauren Jane (2012)

    Undergraduate thesis
    University of Otago

    Background: Few studies have attempted to define the intraosseous course of the chorda tympani (CT) a bilateral nerve that conveys taste from the anterior two-thirds of the tongue and provides parasympathetic innervation to the submandibular and sublingual salivary glands. This is surprising given that iatrogenic injury of the CT is a well-known complication of middle ear surgery and results in taste disturbance, dry mouth, and unpleasant sensory symptoms. Aims: The principle aim of the study was to accurately define the posterior canaliculus (PC) of the CT in the temporal bone to provide guidance for middle ear surgery. A secondary aim was to evaluate the proximity of the PC to a groove which is drilled in the temporal bone during the insertion of a subannular ventilation tube (an otosurgical procedure). Methods: 40 cadaver temporal bones from 27 cadavers (15 male, mean age 75 years, 13 bilateral) were scanned using a SkyScan micro-CT scanner. 3-D multiplanar reconstructions were generated using the software platform Amira 4.1. Images were oriented to Reid’s axial, sagittal and coronal planes using data from the orientation of the semicircular canals and a mathematical algorithm. The PC of the CT was measured in relation to reproducible bony landmarks, the stylomastoid foramen, tympanic sulcus, external auditory meatus and facial nerve canal, using image processing programmes ImageJ and Fiji, and Amira. In the applied follow-up study, 10 of the 40 temporal bones were drilled by an ear surgeon as for subannular ventilation tube placement. The temporal bones were then reimaged and oriented to Reid’s planes as above and the proximity of the drilled groove to the PC analysed. The angulation of the tympanic membrane was also measured in all 40 cadaver temporal bones. Results: Quantitative data showed that the CT originated from the facial nerve outside the skull in 6 specimens and from within the facial canal in 34. In the latter, the PC originated a mean of 3.2 ± 1.8mm above the stylomastoid foramen at an angle of 18 ± 9° to the sagittal plane and 13 ± 6° to the coronal plane. The posterior canaliculus was 12.3 ± 3.8mm long with maximum and minimum diameters of 1.2 ± 0.2mm and 0.4 ± 0.1mm, respectively. As the PC travelled cranially it became closer to the tympanic sulcus and external auditory meatus and more distant from the facial nerve canal. It entered the middle ear at a height 62 ± 10% of the height of the tympanic membrane. In the applied study, drilling the temporal bone for subannular ventilation tube placement had the potential to cause iatrogenic injury in two cases (20%). The tympanic membrane was found to be angled at a mean value of 34° (range 16 to 45°) to the parasagittal plane and 42° (range 22 to 58°) to the axial plane. Conclusions: This novel micro-CT study defines the precise anatomy of the PC which houses the CT. These data and those from the applied study relating to subannular tube placement may help the surgeon protect the CT from iatrogenic injury. This thesis has also documented, more precisely than ever before, the angle of the human tympanic membrane which lies at a greater angle to the axial and parasagittal planes than previously reported.

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  • Maternal obesity predisposes offspring to obesity; understanding the role for elevated Interleukin-6

    Campbell, Samantha Rosalind Shanti (2012)

    Undergraduate thesis
    University of Otago

    Obesity has quickly become an epidemic, and there has been a concomitant increase in the prevalence of obesity during pregnancy. Together human and animal studies have revealed that over-nutrition is a high risk factor for the development of obesity in offspring. The arcuate nucleus of the hypothalmus is located near a leaky brain-blood barrier, allowing neurons to receive blood-borne signals from the body, such as insulin, leptin and glucose, about energy expenditure. There are two populations of neurons within the arcuate nucleus that are specific for modulating weight regulation; neuropeptide Y (NPY) and proopiomelanocortin (POMC) neurons. The early development of the NPY and POMC-containing neurons places these peptidergic systems as likely targets for maternal obesity influenced disruption during embryonic and fetal development. Inflammation can be caused by the secretion of pro-inflammatory cytokines from adipose tissue macrophages, and there is evidence of elevated low-level chronic inflammation in obese individuals. A high fat diet (HFD) has also been shown to stimulate a local pro-inflammatory condition in the hypothalamus, resulting in changes in the hypothalamic regulation of energy homeostasis. Previous studies have shown that one of these cytokines, specifically Interleukin 6 (IL-6) is elevated in the maternal and placental circulation of obese mothers, in comparison to mothers of a normal weight. As elevated pro-inflammatory cytokines are a hallmark of maternal obesity, it is proposed that IL-6 may be involved in the mechanism influencing the development of weight regulation centres within the fetal brain, predisposing offspring to obesity throughout life. Therefore we hypothesised that cells within the arcuate nucleus of the fetal brain are responsive to IL-6. In vitro organotypic slice culture experiments were carried out to test this hypothesis. Fetal brains were sectioned on a Vibratome and the response of IL-6 was tested at different concentrations on the arcuate nucleus. The phosphorylation and translocation of Signal Transducer and Activator of Transcription 3 (STAT3) to the nucleus is a marker for IL-6 receptor signalling. Thus single-label immunocytochemistry detected immuno-positive phosphorylated STAT3 cells and bilateral cell counts of the fetal arcuate nucleus were performed. These studies revealed that there was no increase in the number of immuno-positive pSTAT3 cells under stimulation of IL-6 in the arcuate nucleus. Results did show a reduction in the number of immuno-positive pSTAT3 cells seen in higher concentrations of IL-6 (10 ng/ml and 100 ng/ml) in the fetal arcuate nucleus. Therefore, we conclude that cells within the fetal arcuate nucleus are responsive to IL-6 at concentrations of 10 ng/ml and 100 ng/ml IL-6.

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  • VEGF Levels in Women with Gynaecological Cancers

    Lee, Jeffrey (2012)

    Undergraduate thesis
    University of Otago

    Background: High blood levels of Vascular Endothelial Growth Factor (VEGF) have been reported in patients with gynaecological cancer and have been correlated with advanced disease and poor outcome. However, results are few and varied and most studies used single measurements. There is also debate as to whether serum or plasma measurement reflects circulating VEGF. Aims: To describe and compare the properties of serum and plasma VEGF in women with ovarian and endometrial cancer. To clarify their relationships with platelets and investigate their correlation with disease activity. In addition we wished to investigate the effect of green tea (which has known angiogenic activities) consumption on blood VEGF. Methods: VEGF was measured by ELISA method in serum and plasma in women with gynaecological cancers. Serial measurements were taken in women with endometrial or ovarian cancer, and in women without cancer. Blood samples were also obtained in women before and after surgery for endometrial or ovarian cancer. The association of platelets and CRP to blood VEGF was determined using combined data. In addition, the effect of green tea on serum and plasma VEGF was evaluated in women with persistent cancer who were treated with 6 days oral green tea extracts equivalent of 900mg EGCG daily. Results: The median week to week coefficient of variance (CV) was approximately 10% for serum and 30% for plasma VEGF. There was significant overlap in VEGF concentrations between women with disease and control. Serum VEGF but not plasma correlated with platelets and CRP and there appeared to be a multiplicative relationship between plasma and serum VEGF. There was no significant difference between blood VEGF before and after surgery. Short term green tea extracts were safe but did not lead to significant changes in blood VEGF. Conclusion: Blood VEGF measurements are elevated in some women with advanced gynaecological cancers, single measurements appear a reliable indication of the levels in different patients but levels did not appear to be a good indicator of change in tumour load within individual patients. Serum VEGF varied with platelet count and CRP and may be reflection of the systemic response to advanced malignancy. It is not clear to what extent plasma VEGF reflects circulating VEGF. We did not see a reduction in blood VEGF after consumption of green tea. Future studies are needed to assess to what extent plasma VEGF reflect circulating VEGF, and the effect of green tea extracts.

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  • Induced Pluripotent Stem Cells: An Alternative to Embryonic Stem Cells?

    Bridge, Sophie Elizabeth (2012)

    Undergraduate thesis
    University of Otago

    Human stem cell research is a new field with many promises, but progress towards a clinical setting has been complicated by scientific and ethical challenges. The most heated discourse over stem cell research to date has focused on the source of human embryonic stem cells (ESCs). Different views on the moral status of the human embryo have plagued all aspects of the debate (and decision-making) on stem cells. Opponents of ESC research consider that embryos symbolize the start of life and therefore should not be sacrificed as a source of stem cells. In 2006, a way of de-differentiating somatic cells to a pluripotent state was realized. The advent of these induced pluripotent stem cells (iPSCs) appeared to circumvent concerns over embryo destruction, and hence iPSCs have been touted as an ideal (and ethical) way forward for stem cell research. However, at least for the foreseeable future, scientific investigations involving iPSCs are likely to drive further embryo destruction. As a result, iPSC research (on its present trajectory) is inevitably (and perhaps surprisingly) complicit in embryo destruction and is inextricably locked in to the moral status debate. Furthermore, iPSCs not only have scientific challenges of their own, but they have the potential to lead to the development of controversial assisted reproductive techniques (ARTs). In other words, the emergence of iPSCs has not only failed to circumvent the central moral concern with ESCs, but they have also raised a host of other novel ethical complexities. Consequently, there are a number of flaws in the commonly heard argument that ESCs are ethically problematic and that iPSCs are a morally superior option. The current state of knowledge is hugely problematic due to moral complicity and scientific challenges, and the stem cell field is plagued by uncertainty and risk. The moral frameworks that have been conventionally used as a basis of stem cell ethics have so far proved inadequate, failing to provide clear guidance on how best to come to terms with the notion of respect for embryos that are being destroyed, and on the potential of iPSCs to create embryo-like entities.

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  • Preimplantation Genetic Diagnosis: From Clinic to Eugenic Fears and Disability Concerns

    Anderson, Hamish (2012)

    Undergraduate thesis
    University of Otago

    Preimplantation genetic diagnosis (PGD) is an assisted reproductive technology introduced to detect embryos with genes associated with certain genetically-based diseases. The rationale for this procedure that has been carried out for over 20 years is to bring about the birth of children not affected by the genetic condition in question. The inevitable selection of one embryo over another has constituted the crux of the main opposition to PGD over the years, especially among those for whom all embryos have a moral value equivalent to that of fully developed humans. However, with time this core ethical dilemma has been joined by others, characterised in particular by fears about the eugenic nature of PGD, and concerns that its use devalues people with disabilities. The practical issues that are most relevant emerge in connection with Huntington’s disease testing, HLA-typing and preimplantation genetic screening (PGS). In order to look in some detail at the major issues in these areas, considerable attention is paid to the current state of the scientific base of PGD, and the dominant issues that arise in the clinic. In considering general ethical issues, there is discussion around principles such as autonomy, non-maleficence and truthfulness. In terms of eugenic fears, the controversy surrounds the concern that PGD is a reincarnation of the eugenics of the early 20th century, which culminated in the horrors of the Holocaust. This worry is evaluated for its legitimacy, and then reanalysed in the context of Agar’s definition of liberal eugenics. Overall, the fears about eugenics are shown to be unfounded, due to the current lack of class bias, lack of coercion and the well-grounded science upon which the procedure is based. The final issue analysed is what is termed the ‘expressivist objection’. This describes arguments that claim that the way PGD is practised causes harm to the disability community. This view emerges from the social model of disability, which stands in opposition to the prevalent medical model. In drawing together these various strands, I conclude that the potential harms expressed are not sufficiently serious to outweigh the advantages that PGD brings. It is concluded that PGD is currently practised in a responsible and measured way that effectively balances potential dangers with the immense benefits that can be achieved. On the other hand, major changes in the reasons for undertaking PGD in the future may substantially alter the ethical horizon.

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  • Structure, stratigraphy and metamorphism in the upper Hakataramea valley area, South Canterbury, New Zealand

    Fagan, Robert Keith (1971)

    Undergraduate thesis
    University of Otago

    vi, 73 leaves ; 30 cm. Includes bibliographical references. University of Otago department: Geology.

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  • Mepilex Lite: The Effect of Mepilex Lite Dressings on Acute Radiation-Induced Skin Reactions in Women Receiving Post-Mastectomy Irradiation

    Paterson, Dean (2012)

    Undergraduate thesis
    University of Otago

    Acute radiation-induced skin reactions are a common side effect of breast radiation therapy. Reactions range from erythema, through dry desquamation to moist desquamation and can be a source of significant pain, discomfort and psychological distress, sometimes resulting in a treatment break. There is no standard method for the prophylaxis or management of these reactions. Practice is often based on historical or anecdotal evidence and considerable variation in skin care practices exist. The aim of this trial was to investigate whether Mepilex Lite dressings are superior to standard care in reducing the extent of acute radiation-induced skin reactions in patients receiving treatment for breast cancer post-mastectomy. Mepilex Lite (Mölnlycke Health Care AB, Göteborg, Sweden) is a thin, self-adhering, absorbent, soft silicone dressing designed for the management of wounds and burns. It was hypothesised that Mepilex Lite would reduce reactions by protecting the irradiated skin against mechanical damage caused by friction and abrasion from clothing or adjacent tissue. A multicentre, open-label, randomised, intra-individual comparison of 80 patients is being conducted. This thesis analyses a subset of 10 patients recruited at the Wellington Blood and Cancer Centre. At the first sign of erythema, the erythematous patch was divided into two equal halves; one half was covered in Mepilex Lite, the other treated with aqueous cream. In the event of moist desquamation, Mepilex Lite continued over the intervention patch and the department’s standard dressing was used as the control. The Modified Radiation-Induced Skin Reaction Assessment Scale (RISRAS) was used to assess the outward signs (researcher component) and subjective symptoms (patient component) of the skin reaction three times a week during radiation therapy and once a week post-treatment until the reaction resolved. Patients also filled out an exit questionnaire on different aspects of the trial and the skin care agents. Mepilex Lite dressings produced a significant decrease in the peak (p=0.019) and average (p=0.031) patient component of the RISRAS. This aligned with reports from the exit questionnaire. An anecdotal reduction in redness was supported by lower average (p=0.012) erythema RISRAS scores under the Mepilex Lite dressings. However, the decrease in peak erythema score and total researcher scores did not reach statistical significance in this small cohort. The impact of Mepilex Lite on moist desquamation could not be assessed in this small cohort due to the low incidence of moist desquamation in the study patches. The results suggest that regardless of whether Mepilex Lite dressings reduce the visible signs of radiation-induced skin reactions in the final analysis of all 80 patients, its use may be justified based on the symptomatic relief it appears to provide in this small cohort.

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  • Reproductive effects of ghrelin in the hypothalamus

    van Rooyen, James (2012)

    Undergraduate thesis
    University of Otago

    Ghrelin is a metabolic hormone released by the stomach at increased levels during times of fasting. It is known that ghrelin has suppressive effects on reproduction, for example by decreasing luteinizing hormone (LH) pulsatility. Whether it also inhibits the neuroendocrine control of ovulation is unknown. We set up three experiments to delve further into ghrelin’s actions on the control of reproduction by the hypothalamus, the region of the brain critical for control of the reproductive axis. In the first experiment we established a protocol to abolish the preovulatory LH surge in mice by fasting them for 36 hours or treating with 20mg/kg ghrelin at 2 hourly intervals on the afternoon of the surge. We then examined whether restoration of ghrelin levels to a non-fasted state by using mice with a knocked-out ghrl gene, restoration of leptin levels by administration of 1mg leptin/kg in at ~12 hourly intervals, or restoration of both would restore the surge in the fasted mice. We found that neither ghrelin knockout or leptin replacement nor their combination was able to restore the surge in fasted mice, while ghrelin injections prior to the expected LH surge, given to fed control mice, were able to abolish the preovulatory LH surge. It is proposed that the effects of ghrl knockout and leptin replacement be re-examined in a shorter (and therefore more physiologically relevant) fast model. This suggests that ghrelin is sufficient but not necessary to inhibit the preovulatory LH surge in fasted mice. In the second experiment we attempted to systematically examine various potential signalling markers of ghrelin activity within the hypothalamus. We implanted intracerebroventricular (ICV) cannulae into two groups of Sprague-Dawley rats and administered 3nm ghrelin into one group, and vehicle only into the other group, and perfused the rats an hour later. The brains were then stained immunohistochemically for either phosphorylated extracellular signal-related kinase 1/2 (pERK 1/2) or phosphorylated cAMP-response element-binding protein (pCREB). The series were then co-stained for either tyrosine hydroxylase (as a surrogate for anteroventral periventricular kisspeptin neurons), gonadotrophin-releasing hormone (GnRH), corticotrophin-releasing hormone (CRH), RF-amide related peptide 3 (RFRP-3), or kisspeptin. No change was found in CREB phosphorylation with ghrelin administration, but did find statistically significant decreases of ERK 1/2 phosphorylation in the arcuate nucleus (ARC), ventromedial hypothalamic nucleus (VMH), as well as the dorsomedial hypothalamic nucleus (DMH). The significance of these findings are difficult to speculate, save to say that ERK 1/2 phosphorylation appears to be negatively regulated by ghrelin activity within the hypothalamus. For our third experiment, we proposed a model through which ghrelin decreases LH pulsatility, namely that it stimulates CRH neurons which then suppress arcuate kisspeptin neurons which are thought to drive the GnRH pulse generator in rodents. To test this hypothesised pathway 3nmol ghrelin with or without 27nmol of the CRH-R2 antagonist astressin-2B, the antagonist alone, or 5μg CRH alone was administered ICV into groups of Sprague-Dawley rats. LH levels in the blood were measured 1 hour later as well as Kiss1 mRNA levels in the caudal and rostral hypothalami of the rats. Our results were statistically insignificant but trends in the LH levels suggest that CRH-R2 is a mediator of ghrelin’s suppression of LH pulsatility. Overall, we have examined varying facets of ghrelin’s neuroendocrine reproductive roles and found several interesting new additions to these.

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  • Prismatic displacement effect of progressive multifocal glasses on fall risk in elderly people

    Ellison, Ashton (2012)

    Undergraduate thesis
    University of Otago

    World Health Organization statistics show that falls are the second leading cause of unintentional injury-related deaths worldwide. Multifocal glasses (bifocals, trifocals, and progressive addition lenses (PALs)) increase the risk of a fall in elderly people but how they do so is unclear. To explain why glasses with a PAL increase the risk of a fall and whether this can be attributed to false projection, this study aimed to 1) map the prismatic displacement of a PAL, 2) test whether this displacement impaired the response to loss of balance, and 3) test whether PALs alter stability. The reaction time and accuracy of healthy ≥75 year olds (n = 31 participants) were measured when grasping for a bar and touching a black line. These were positioned according to the maximum and minimum prismatic displacement effect through the PALs, mapped using a focimeter. Anterior posterior (AP) deviation was measured while standing on a balance platform. Participants performed each test twice, alternatively wearing their PALs and newly matched single vision (distance) glasses in random order. Results showed that PALs have large areas of prismatic displacement, especially in the central visual axis. Reaction time was faster for PALs compared to single vision (distance) glasses (mean difference ± SEM, horizontal grab bar in centre -0.101 ± 0.050 s, P = 0.011, repeated measures analysis adjusted for order of glasses, days since participants updated their PALs and amount of prismatic displacement; horizontal black line 300 mm down from centre -0.080 ± 0.016 s, P = 0.007). There were no differences in the balance measures. PALs have large areas of prismatic displacement, but did not alter stability. Older people appeared to adapt to the false projection of PALs in the central visual axis. This adaptation meant that swapping to new single vision glasses may have affected the visual-spatial stored information. This may lead to a fall, especially in unfamiliar surroundings.

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  • Electing New Zealand's Health Governors: Do elected board members have the appropriate knowledge, skills and experience to govern district health boards?

    Hansby, Oliver Ron (2012)

    Undergraduate thesis
    University of Otago

    The manner by which a health system is governed impacts upon the delivery of health services. New Zealand has a decentralised health system featuring twenty district health boards (DHBs) that are responsible for ensuring the provision of regional health services. Each DHB is governed by a board typically comprised of four appointed board members and seven elected board members. Appointed board members are selected by the government, and must be deemed to have the appropriate knowledge, skills, and experience. On the other hand, elected board members are chosen by the public in triennial DHB elections. Aside from some statutory disqualifiers, there are no prerequisites to standing in these DHB elections. Objectives: This dissertation contributes to the debate on whether elected board members have the appropriate knowledge, skills, and experience to govern DHBs. This dissertation describes the past experiences of elected DHB board members and identifies which of these past experiences are associated with successful candidacy. This dissertation also explores whether elected and appointed DHB board members perceive that they have the appropriate knowledge, skills, and experience to govern DHBs. Methods: The past experiences of elected DHB board members were assessed through an analysis of the candidate profiles submitted prior to DHB elections. Then, the association between these past experiences and the outcome of DHB board candidacy was studied through logistic regression. Finally, all current DHB board members were invited to participate in a short survey focused on DHB governance. Conclusions: According to their candidate profiles, elected DHB board members have a range of past experiences, with the most common being past DHB board membership. Of the past experiences identified, past DHB board membership, past service as an elected representative, and experience as a doctor or a nurse were associated with increased odds of success in at least two of the past three DHB elections. Conversely, past experience in both health and non-health related business and management was associated with decreased odds of success in at least one of the past three DHB elections. Regarding the perceptions of current DHB board members, most elected and appointed DHB board members perceive themselves to have the appropriate knowledge, skills, and experience to govern DHBs. Some appointed DHB board members are, however, sceptical of the competence of their colleagues, particularly those that are elected DHB board members.

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  • Mechanisms of Hereditary Diffuse Gastric Cancer Initiation: The role of E-cadherin in the Epithelial-Mesenchymal Transition

    Beetham, Henry Guy Scott (2012)

    Undergraduate thesis
    University of Otago

    Hereditary diffuse gastric cancer (HDGC) is a dominantly inherited cancer syndrome caused by germline mutations in the CDH1 gene which encodes the calcium-dependent, cell-cell adhesion protein E-cadherin [1,2]. Early stage HDGC is characterized by multiple foci of stage T1a signet ring cell carcinomas (SRCC). These foci are relatively indolent [3], however some eventually undergo an epithelial-mesenchymal transition (EMT) changing them into aggressive mesenchymal cells. At present it is not known definitively how the loss of E-cadherin and CDH1 germline mutations contribute to tumour initiation primarily in HDGC. The aim of this research was to determine whether the abrogation of E-cadherin expression alone is sufficient to induce an EMT, or if other mechanisms are also required. In order to analyse the early events of HDGC in vitro, an isogenic breast cell line model system with CDH1 knockout (-/-) cells was chosen. E-cadherin loss was found to affect cell morphology, proliferation rate, nucleoli number and cell adherence of the mammary epithelial cells. Transcriptome profiling performed on the isogenic cell lines showed E-cadherin loss resulted in an upregulation of genes involved in the tight junction complex such as claudin and occludin. The majority of EMT markers expected to be involved in cells undergoing an EMT were not upregulated. CDH1 loss also affected migration rates and growth in 3D culture. Overall, this study showed that E-cadherin loss alone was insufficient to cause a complete EMT in our model system. However, some genes associated with gastric and breast cancer progression were differentially expressed: S100-calcium binding proteins, matrix metallopeptidases (MMPs), and mucins. Hence, these CDH1 -/- cells show an increased ‘cancer-like’ phenotype but still remain relatively indolent, at least in the observed time frame.

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  • Phenotyping Asthma using an Electronic Nose

    Liley, Albert James (2012)

    Undergraduate thesis
    University of Otago

    Rationale: Asthma is a chronic respiratory condition affecting many millions of people worldwide. The recommended long-term preventative treatment for asthma is corticosteroid medication. Improvement in asthma symptoms in response to corticosteroids is not universal, and prescription to non-responsive patients is costly and potentially dangerous. The assessment of whether patients will respond to corticosteroid treatment is an important clinical problem. This study investigated the utility of a gas sensor array, the ‘Electronic nose’, in predicting response to steroid among asthmatics and in differentiating asthmatics from healthy controls using exhaled breath. The anti-inflammatory actions of steroids and the biochemical basis of steroid response are complex and may be better quantified by the electronic nose than by single biomarkers. In parallel with the assessment of steroid response a study was conducted on the ability of the electronic nose to predict sputum eosinophil counts among asthmatics. Eosinophil count is a predictor of steroid response and can be used as a guide to asthma treatment. Statement of problems: Can steroid-responsive and non-steroid responsive asthmatics be distinguished using electronic nose analysis of exhaled breath? Is sputum eosinophil count able to be predicted by electronic nose analysis of exhaled breath? Methods: 47 patients (27 asthmatics, 20 healthy controls) participated in the study. Asthmatic patients completed a two-week trial of oral prednisone. Asthmatics were classified as steroid responsive if FEV1 improved by 15%, PC20AMP improved by >300%, or ACQ (asthma control questionnaire) improved by >0.5 points over the steroid course. 16 asthmatics were steroid responsive and 11 asthmatics were steroid unresponsive. Breath samples were taken before and after the steroid course. A sputum sample was taken prior to the steroid course. Asthmatics were defined as eosinophilic if their sputum cell count contained more than 3% eosinophils. Healthy controls provided a single breath sample and sputum sample. Main results: Steroid responsive and non-steroid responsive asthmatics were unable to be distinguished either before or after the steroid course (no significant principal component differences, Mdistances0.2). Healthy controls were significantly differentiated from pre-steroid asthmatics (PC2, PC4, PC6, p=0.0090, 0.000060, 0.0090 respectively, M-distance=4.66,p=0.031) and less differentiated from post-steroid asthmatics (PC6, p=0.0016, Mdistance=3.80,p=0.16). A multilayer perceptron based predictive model for the comparison was associated with a cross-validation value (CVV) of 83% between controls and pre-steroid samples and 70% between controls and post-steroid samples. Improvement in ACQ (PC6, p=0.0041) and improvement in FEV1 (PC6, p=0.045) could be detected based on differences in samples before and after the steroid course. A principal component from pre-steroid asthmatics was strongly correlated with sputum eosinophil counts (coefficient=0.615, p=0.0082). Breathprints from eosinophilic and noneosinophilic asthmatics were significantly differentiated (PC4, p=0.0033, M-distance=2.00, p=0.0020). A predictive model for the comparison was associated with a CVV of 77%. Conclusions: Steroid responsive and non-steroid responsive asthmatics cannot be differentiated on the basis of exhaled breath analysis by electronic nose. Healthy controls and asthmatics can be significantly differentiated on this basis. Electronic nose readings are correlated with sputum eosinophil counts and eosinophilic and non-eosinophilic asthma can be significantly differentiated.

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  • Cardiac function and β-adrenergic receptor responsiveness in the isolated human diabetic myocardium

    Wang, Heng-Yu Simon (2012)

    Undergraduate thesis
    University of Otago

    The prevalence of type 2 diabetic mellitus is closely associated with cardiovascular complications. Diabetic patients with preserved ejection fraction (EF) are at high risk of developing heart failure. Until now, little is known about the etiology of the impaired cardiac performance in diabetic patients with preserved EF. Hence this study aimed to address this by investigating the cardiac function of these diabetic patients. We hypothesised that isolated cardiac muscles from diabetic patients will have reduced cardiac performance both at basal conditions, and after β-adrenoceptor (β-AR) stimulation mimicking a physiological stress response. Using isolated cardiac muscles obtained from right atrial appendages of patients undergoing coronary artery bypass grafting, functional characteristics of non-diabetic (n = 8) and diabetic myocardium (n = 6) were compared. (Samples from patients who had acute coronary artery disease and reduced EF (< 40%) were excluded.) Contractile and relaxation parameters of both cohorts were first determined under basal conditions, then in response to a β-AR agonist (dobutamine, 1x10-7 to 1x10-5 M). In addition, Langendorff-perfused isolated hearts from non-diabetic and diabetic ZDF rats were also implemented to compare cardiac function. Compared to non-diabetics patients, the developed force (Fdev) of diabetic human cardiac muscles was not different. However, a slower rate of maximum contraction (+dF/dtmax) and relaxation (-dF/dtmax), as well as prolonged relaxation times during the force-length relationship were observed in diabetic muscles (p < 0.05). A significantly longer relaxation time was also observed during force-frequency relationship in the diabetic muscles (p < 0.05). Moreover, diabetic cardiac muscles were less responsive to β-AR stress response, as shown by the reduced increase in Fdev, +dF/dtmax and -dF/dtmax, as well as smaller reduction in relaxation times. These observations were consistent with the results obtained from the isolated rat hearts. Ultimately, this study showed that diabetic patients with adequate systolic function, as indicated by preserved ejection fraction, suffer from diastolic dysfunctional characteristics and exhibit a reduction in the β-AR.

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  • The arterial supply of the ulnar nerve and cubital tunnel ischaemia

    Harris, Chelsea (2012)

    Undergraduate thesis
    University of Otago

    Background: The ulnar nerve is a major nerve in the upper limb and is susceptible to injury, particularly in the region of the cubital tunnel. A suspected mechanism of injury at this site is ischaemia. Whilst this can be caused by mechanical stress (stretching, compression) on the nerve in the tunnel, there may also be fundamental differences between and within individuals in the arterial supply of the nerve in this region. The nature of the arterial supply to the ulnar nerve has received relatively little attention, and a more detailed understanding could aid in the diagnosis, treatment and prevention of ischaemic injury to the nerve. Aims: The first aim of this study was to investigate the extrinsic arterial supply to the ulnar nerve by dissection. The second aim was to analyse the intrinsic arterial anatomy of the ulnar nerve in the cubital tunnel by semi-quantitative histology. Methods: Twelve cadaver upper limbs (paired upper limbs from six body donors; four female, two male; age range 66 – 90 years) were dissected to record the presence of visible arterial branches contacting the ulnar nerve and their arteries of origin. The distances between bony landmarks and the origins of the major arterial branches supplying the ulnar nerve were measured, together with their diameters. For the study of intrinsic arterial supply, 5µm thick histological sections of the nerve were taken from standardised sites within the cubital tunnel and 5cm proximally and distally. The sections were stained with haematoxylin and eosin, and the combined total cross-sectional area (CSA) of all arteries with a minimum CSA of 80µm² was measured. This was then expressed as a percentage of the total nerve CSA. Results: The extrinsic arterial anatomy of the ulnar nerve was found to be very variable. The superior ulnar collateral artery (SUCA), inferior ulnar collateral artery (IUCA), posterior ulnar recurrent artery (PURA), brachial and ulnar arteries all contributed, although SUCA was the most consistent of these (9 of 12 specimens). There were no detectable branches from the anterior ulnar recurrent artery (AURA). Variations were found in the extrinsic arteries of some specimens: four limbs had high proximal brachial bifurcations; two had unusual SUCA origins; and in nine the PURA and AURA originated from a common stalk. The mean CSA of arteries within the ulnar nerve in the cubital tunnel was not significantly different from standardised sites proximal and distal to the tunnel (cubital tunnel vs. proximal, p=0.76; cubital tunnel vs. distal, p=0.24). However, in two specimens with aberrant SUCA origins there was a significantly greater proportion of CSA occupied by arteries in the cubital tunnel. Extrinsic and intrinsic supply were found to have a direct positive relationship in nine of the 12 specimens: the greater the number of arterial branches supplying the ulnar nerve and the larger their diameter, the greater the proportional CSA of the intraneural arteries. Conclusions: The extrinsic arterial supply of the ulnar nerve is very variable. The SUCA, IUCA, PURA, brachial and ulnar arteries all contribute but the SUCA is most consistent between individuals. The intrinsic arterial supply (as determined by the proportion of CSA occupied by intraneural arteries) does not appear to be significantly different in the cubital tunnel compared to adjacent proximal and distal sites. Accepting the relatively small sample size in this study, these results suggest that the nature of the intrinsic arterial supply to the nerve is unlikely to be a major factor in the predisposition to ulnar nerve ischaemia, but the variability of the extrinsic arterial supply of the nerve could be important.  

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