Browsing by Author "Hall, Pauline de la Motte"

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    Chronic hepatitis at Groote Schuur Hospital: 1978-1996 : a literature review of the syndrome, its clinical spectrum and management at Groote Schuur Hospital
    (1999) Hairwadzi, Henry N; Hall, Pauline de la Motte
    Chronic hepatitis has multiple aetiologies which include viral hepatitis (hepatitis B, B+D and C), autoimmune hepatitis and drugs. In sub-Saharan Africa the major aetiological factor is chronic hepatitis B virus infection. In this region 10-15% of the population is chronically infected with the virus and 76% have serological evidence of past exposure to the hepatitis B virus. HDV infection has not been documented in Southern Africa but studies from Northern Africa show antibody positivity for HDV of 21-31 % in patients with chronic HBV infection. Drug-induced hepatitis is also increasingly being recognised as a significant entity. This study arose from the observation that there are a significant number of patients with autoimmune hepatitis on follow-up at the Groote Schuur Hospital liver clinic. This group includes patients who test negative for the standard autoimmune markers done at Groote Schuur Hospital but have liver histology that is typical of classical autoimmune hepatitis. They also show a clinical and biochemical response to steroid and azathioprine therapy that is indistinguishable from that seen in classical autoimmune hepatitis cases on similar treatment. This study is retrospective and covers the period 1978 - 1996. The patients studied are those with chronic hepatitis as defined by the International Working Party in 1995, i.e. patients with necro-inflammatory disease of the liver lasting at least 6 months. This includes hepatitis B, B + D, C, autoimmune hepatitis and drug-induced liver disease. Several other liver diseases that may present with clinical and histological features of chronic hepatitis are specifically excluded. These include Wilson's disease, Primary biliary cirrhosis, Primary sclerosing cholangitis, alpha-1-antitrypsin deficiency, alcohol abuse and iron over load states.
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    Cyclooxygenase-2 in cervical neoplasia and the relationship with specific human papillomavirus types
    (2000) Hofmeyr, Michael Devitt; Hall, Pauline de la Motte
    Includes bibliographical references.
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    The db mouse as a model for steatohepatitis
    (2006) Sutherland, Jason Robert; Hall, Pauline de la Motte; Marais, David
    Fatty liver disease is a collective phrase for a spectrum of diseases characterised by increased liver fat content. It ranges from fatty infiltration of the liver to an inflammatory condition, steatohepatitis, which may lead onto cirrhosis. Although not associated with alcohol consumption, non-alcoholic steatohepatitis (NASH) has strong associations with obesity, diabetes and dyslipidaemia. Overlapping pathological mechanisms may be involved. The course of the disease will remain unpredictable, and specific treatment will only be able to be instituted once the pathogenesis is fully understood. This thesis reviews current understanding of the pathogenesis and explores the suitability of a recently defined obese diabetic mouse model for its value as a model in the heterozygous and homozygous states. Observations revealed that the db/wt phenotype has a larger mass than the wt/wt and responds with hyperglycaemia. Lipid accumulation occurs in this model when alcohol is administered and lipid peroxidation occurs but histological changes of steatosis and steatohepatitis do not occur. The db/db model is phenotypically distinguished by a large amount of fat storage, diabetes and macrovesicular steatosis that has more lipid peroxidation but no steatohepatitis even when alcohol further increases lipid peroxidation. The model, as explored, did not reveal steatohepatitis either alone, or with alcohol as a single additional stressor, but both the db/wt and db/db mouse model could be further investigated to explore whether additional stressors could induce steaotohepatitis in this model.
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    The development of a "new" stain and its comparison with currently available stains for the evaluation of mycobacteria in processed tissue
    (2006) Jamieson, Craig; Hall, Pauline de la Motte
    Includes bibliographical references.
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    Hereditary non-polyposis colorectal carcinoma (HNPCC) : morphological and immunohistochemical studies
    (2005) Holm, Hannes; Hall, Pauline de la Motte
    Families with hereditary non-polyposis colorectal carcinoma (HNPCC) are not uncommon along the West-Coast of South Africa. These patients present with early onset carcinomas mostly colorectal, predominantly in the right colon. They may develop tumours of other organs, including uterus, breast, stomach and skin. To evaluate and compare the microscopic characteristics of three groups of colorectal carcinomas (HNPCC, early onset colorectal carcinomas and sporadic colorectal carcinomas). 2. To determine the features most characteristic of the group.
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    An immunohistochemical study of beta-catenin in HNPCC colon tumours
    (2004) Watkins, Jennifer G; Hall, Pauline de la Motte
    Beta-catenin is normally complexed with adenomatous polyposis coli (APC) protein and E-cadherin adhesion molecule, and localized on the cell membrane. If APC/beta-catenin is disrupted, beta-catenin transfers into the nucleus, where it functions as a transcriptional activator, causing unregulated cell proliferation. The localisation of beta-catenin in H NPCC adenomas has not been studied but a shift in beta-catenin to the nucleus has been previously demonstrated in a range of col 0 recta I cancers, including those in HNPCC. The aim of the first part of the study was to determine whether there is a beta-catenin shift occurring as an early event in HNPCC tumours. Coded sections of tumours were immunohistochemically stained with antibody against beta-catenin and counterstained in haematoxylin. 14 HNPCC adenomas, 13 HNPCC carcinomas, 10 FAP adenomas, 10 FAP carcinomas, 10 sporadic adenomas and carcinomas and 10 juvenile polyps -three with dysplasia and seven without- were studied. A score was given for loss of membrane staining (0-1), presence of cytoplasmic staining (0-2) or nuclear staining (0- 2) and a total out of five obtained. An shift in beta-catenin was demonstrated at the adenoma phase in HNPCC. HNPCC, tumours were compared with sporadic tumours and a statistically significant similarity in prevalence of beta-catenin shift found in adenomas and carcinomas. The early shift in beta-catenin in HNPCC led to the second part of the study evaluating the "down-stream" effects of this shift in HNPCC tumours. TheHNPCC sections were immunohistochemically stained with E-cadherin, cmyc and cyclin 01. The results showed a positive correlation between Ecadherin loss, increased cyclin 01 and a shift in beta-catenin. No significant change in c-myc or correlation between c-myc and a shift of beta-catenin was found. In conclusion the study indicates that disruption of the APC/beta-catenin pathway plays a similar role in HNPCC tumours to that in sporadic tumours. A notable exeption is the effect on c-myc and further study is needed in this regard.
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    Nonalcoholic steatohepatitis (NASH) : animal studies of interactive hepatoxicity
    (2004) Clarkson, Vivian; Hall, Pauline de la Motte; Marais, David; Shephard, Enid
    The term "Nonalcoholic steatohepatitis" (NASH) describes a form of liver disease indistinguishable from alcoholic liver disease, but present in persons who consume insignificant amounts of alcohol. The spectrum of non-alcoholic liver disease ranges from non-progressive steatosis, through to NASH and sometimes to cirrhosis. Risk factors predisposing to NASH include obesity, diabetes mellitus, hypertriglyceridermia and procedures leading to rapid and profound weight loss such as gastric bypass and bulimia. Given the high incidence of type II diabetes, obesity and various types of hyperlipidaemia in the Western Cape, NASH has become one of the most commonly encountered liver diseases in the Liver Clinic, Groote Schuur Hospital. Statistics also suggest nonalcoholic fatty liver disease underlies most cases of elevated liver enzymes in many other parts of the world. The exact pathogenic mechanisms involved are not well understood, and no effective treatment options are currently available. However, animal models of NASH now provide unique opportunities for study of this disease in the laboratory setting. This thesis employs a dietary animal model, which restricts methionine and choline intake, to replicate aspects of the injurious process in human NASH. Two lines of inquiry are pursued. The first involves an assessment of the effect of alcohol consumption on fatty liver of non- alcoholic aetiology. Elevated liver enzymes, altered levels of lipid peroxides, and increased cytochrome P450 activity recorded in this study, suggest alcohol may exacerbate nonalcoholic fatty liver disease. The second line of inquiry is an exploration of the role of Tumor Necrosis Factor alpha (TNFα, a cytokine implicated in pathogenesis of alcoholic liver disease and thought to be pivotal in NASH pathogenesis. The role of TNFα in the dietary model of NASH is investigated using mice lacking functional TNFα genes, as well as wild type mice in which expression of this cytokine is induced by endotoxin challenge. Endotoxin challenge does elicit a marked inflammatory response and enhanced generation of lipid peroxides in the fatty liver, both of which may contribute to injury. However, as knockout mice still develop experimental NASH, TNFα cannot be considered the sole driving force required for the development of NASH. This strength of the project lies in the use of a variety of techniques (in the fields of Pathology, Immunology and Lipid Biochemistry) to investigate a range of aspects of NASH. The results of the alcohol study may provide the first empirical evidence supporting the need to restrict alcohol intake in patients with NASH, while the data on TNFα is vital for illuminating the complex, (potentially) counter-intuitive role of this cytokine in NASH. Where definitive conclusions cannot be drawn from the data, the questions posited may constitute the basis for future research.
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    A retrospective histopathological study and selected molecular genetics of archival prostatic cancer tissue
    (2005) Lombard, Elizabeth Helen; Hall, Pauline de la Motte
    The aims of this study were to determine the age at presentation and the racial distribution of prostatic adenocarcinoma in the Western Cape region and correlate this with histological grade; to correlate the expression of androgen receptor, bcl-2, p53 and Cox-2 with the Gleason grade of disease and patient demographic data and to establish a method to determine androgen receptor (AR) gene amplification in formalin fixed prostatic carcinoma tissue.
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    The role of "non-alcoholic steatohepatitis (NASH)" in methotrexate induced liver injury
    (2001) Langman, Gerald; Hall, Pauline de la Motte
    Hepatoxicity, especially liver fibrosis. is the major concern with long-term, low-dose oral methotrexate (MTX) therapy for psoriasis. The histological features are nonspecific and may resemble those of nonalcoholic steatohepatitis (NASH). Moreover most of the risk factors of MTX induced liver injury are also associated with NASH. In this study serial liver biopsies of 24 psoriatic patients on lOng-term MTX were investigated to determine whether they had risk factors for NASH and the histological features of a NASH-like pattern of liver injury that could have been contributing to the prevalence and progression of liver injury that occurred while on MTX.
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    A study of morphological, immunohistochemical and histochemical features of ampullary carcinomas
    (2005) De Klerk, Willouw; Hall, Pauline de la Motte
    The aim of the first study was to examine clinical, histopathological and immunohistochemical features of ampullary carcinomas and to determine whether any of these features had significant prognostiC value. The immunohistochemical panel was selected after a literature review and included p53, Ki-67, MUC1, MUC1core, MUC2 and CA 19.9. The data was analyzed by multivariate analysis.