3. Electronic Theses and Dissertations (ETDs) - All submissions
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Item Addressing cancer treatment in an African setting: a bioinformatics analysis of pharmacogemically relevant varients(2018) Da Rocha, JorgeCancer is a critical health burden in Africa, and mortality rates are rising rapidly. Treatments are severe and expensive, and often cause adverse-drug-reactions (ADRs). These may be attributed to variants in genes that encode proteins involved in key drug pathways. Most pharmacogenomics (PGx) research has been done in populations of European, Asian and African-American ancestry, with sparse data from African populations. Thirteen genes linked with ADRs to medicines used for treating major cancer types were identified: ABCB1, DPYD, TYMS, CYP19A1, GSTP1, CYP1B1, CYP3A4, CYP3A5, ESR1, CYP2D6, SLC19A1 and XRCC1/5. Public domain wholegenome-sequencing data from the 1000 Genomes Project and the African Genome Variation Project were mined to assess eight African populations. Functional annotation was performed with a series of bioinformatics-based scoring tools to assess potential likelihood of deleterious impact. Variants of high likelihood of deleterious impact, including some novel variants were identified. These novel variants, however, are rare and require further validation. Two key African specific variants were identified: the CYP3A5 frameshift variant, rs41303343, which is highly likely to knockout gene function, and the CYP2D6 missense variant rs59421388, which was scored highly likely deleterious by all tools. Both variants are common in Africans, at frequencies above 10%, but lack clinical investigation into their PGx impact. For missense variants with known PGx effects, such as CYP2D6 - rs1065852 and DPYD - rs2297595, African frequencies are significantly distinct from global populations (p < 1x10-4) (with rs1065852 less common, and rs2297595 more common in Africans respectively). There is also variation within Africa, with the rs1065852 A allele being more common in West Africans, while the rs2297595 C allele is more common in East Africans. These data indicate that guidelines for cancer drug safety based on African data is essential for use in Africa, and novel region-specific guidelines should be developed to ensure that Africans could benefit for a personalized medicine approach.Item Aspects of iron metabolism in infection, inflammation and neoplasia. Vol. 2(1987) Baynes, Roy, DennisThis thesis evaluates several aspects of iron metabolism in the setting of infection, inflammation and neoplasia. The work is divided into three major sections. The first investigate the changes in iron metabolism that occur as part of the acute phase response to infection, inflammation and neoplasia. The second section evaluates the normal and pathological biology of the iron-binding glycoprotein lactoferrin. IN the third section the iron transport protein transferrin is investigated in relation to its interaction with the macrophage, a cultured malignant hepatoma cell and a cultured malignant ovarian cell.Item The development and validation of a quality of life assessment instrument for cancer patients in South Africa(2016-11-04) Van Rensburg, Jacoba Johanna Maria JansenBackground: Quality of life (QoL) of cancer patients has been well researched, but not necessarily from the perspective of the patient and not in third world countries. Total care of cancer patients should encompass all aspects of the person, such as physical-, psychological- and social aspects, existential wellbeing and spirituality, in order to ensure optimal QoL. The purpose of the study was to explore QoL from the perspective of the cancer patient who accesses public health care services in South Africa for treatment and to develop and validate an appropriate patient-directed assessment instrument. Method: The study was conducted in two phases. In Phase 1 assessment of QoL was done by means of in-depth qualitative interviews. Open coding and template analysis was conducted \during data analysis and the applicable domains of QoL were identified. In Phase 2 an appropriate QoL assessment instrument was developed for cancer patients in South Africa. The Rasch Measurement Model was utilized for the validation of the instrument. Results: The domains of QoL identified by the cancer patients were: physical, psychosocial, financial, spiritual, existential and emotional. When compared with the domains included in available QoL assessment instruments such as the World Health Organization Quality of Life Instrument (shortened version) (WHOQOL-BREF), the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the Functional Assessment of Cancer Therapy General (FACT-G), the domains identified by cancer patients in South Africa were not fully addressed by these instruments. Significance of results: Culture, psychosocial status, financial aspects and spirituality play a major role in QoL of South African patients, as indicated by this study as well as a previous study on QoL of palliative patients from a resource-poor community in South Africa. These aspects of QoL are not addressed by the most commonly used assessment instruments. The importance of the utilization of an instrument which addresses all the appropriate domains of QoL is highlighted by the study.Item A descriptive study of the distribution and relative frequency of neonatal tumours at Chris Hani Baragwanath academic hospital from 1 January 1988 - 31 December 2012(2014) Schickerling, Tanya MarieBackground: To describe the relative frequency and distribution of neonatal tumours; to determine the age at presentation to the oncology unit and to determine the extent of the delay in referral. To describe any associated syndromes in individual malignancies. Material and methods: A retrospective case series was performed covering 24 years. Demographics, means of diagnosis, treatment and outcome details were reviewed. Results: There were a total of 2626 patients that presented to the oncology department with suspected malignancies. Out of that, 2308 patients were diagnosed with a malignancy and 318 patients had benign tumours. Over the 24 year period 117 tumours were diagnosed in neonates (4,4%). Due to incomplete data 29 patients were excluded. Of the remaining patients, 61 were diagnosed with benign tumours and 27 with malignant tumours. The male to female ratio was 1: 1,5. The mean age at presentation was 16 days. The mean age at diagnosis was 36 days. Histology and radiology were diagnostic in 40,9% and 19,3% respectively. A combination of histology and radiology was used to make a diagnosis in 21,6% of patients, 11,4% of diagnoses were based on clinical examination and 6,8% on biochemistry and haematology. Malignant soft tissue tumours were the most common malignancy (25,9%) followed by renal tumours (18,5%), leukaemia (14,8%), neuroblastomas (11,1%) and retinoblastomas (11,1%). Teratomas (45,9%) and benign vascular tumours (44,3%) were the most common benign tumours. Chemotherapy was used to treat 22 neonates, while 50 underwent surgical removal of the tumour. Half (51,9%) of the patients diagnosed with a malignant tumour died, while 11,1% of patients were iv lost to follow up. Just under 10% (8,2%) of the patients diagnosed with a benign tumour died, while 44,3% of patients were lost to follow up. The overall mortality amongst patients diagnosed with benign or malignant tumours was 21,6%. Conclusion: There is a much higher incidence of benign tumours diagnosed in neonates (69,3%) compared to older children (12,1%). Only 1,2% of all childhood malignancies in our unit occurred in the neonatal period, which is slightly lower than the reported 2%. Two of the major issues that need to be addressed in the future management of neonatal tumours are prompt referral for prompt diagnoses and better follow up.Item Submandibular gland tumours: A clinicopathological review at the Chris Hani Baragwanath and Charlotte Maxeke Johannesburg academic hospital(2014) Atiya, YahyaBackground: Reports relating to Submandibular gland tumours are sparsely reported in the literature. There are some reports of different patterns of tumour types in black/negroid patients, as compared to Caucasian patients1,2,11. Aim: To provide an audit of the histopathological types and the clinical presentations of submandibular gland tumours at our two academic hospitals. Method: An analytical cross sectional study using retrospective clinical data from in-patient ward registers, patient’s hospital records, operating room/theatre registers and the NHLS databases. The study was conducted in the ENT units at the Chris Hani Baragwanath Academic Hospital and the Charlotte Maxeke Johannesburg Academic Hospital, over a chosen period of 7 years from January 2005 to December 2011. All patients who had a submandibular gland excision by members of the ENT department at the two hospitals were included. A total of 61 patient records were examined, of which 26 met the inclusion criteria. Data collected included age, gender, race and histological diagnosis. Data was analysed using standard statistical methods. Results: Twenty six patients were included in this study, comprising 46% females and 54% males. The ages ranged from 22 to 65 years, with a mean of 42.5 years – the majority being in the 22-40 years age group. There was no statistical difference in the age of males and females (p=0.29), nor in black vs. white patients (p=0.29). Benign disease was found in 65.4% of patients, while 34.6% had malignancy. Black patients had a higher ratio of benign disease than white patients, and black males were more likely to have benign disease (83.33%) than black females (50%). However, there was no statistical difference in the ratio of benign to malignant tumours between blacks and whites. Histopathologically, pleomorphic adenoma was the most common benign tumour (82%), while adenoid cystic carcinoma was the most common epithelial malignancy (22%). There was a high incidence of lymphoma (56% of patients) in the malignant group. Local pain (p=0.03) and peripheral neurological deficit (p=0.05) was found to be significantly associated with malignancy. Conclusion: The rate of malignancy in Black patients was found to be lower than that reported in the Western literature, which is in keeping with other studies in non-Caucasian (Black, Asian and Hispanic) populations1,2,9,11. Additionally, Black patients presented at a younger age. Pain and local/peripheral neurological involvement were clinical indicators of malignant disease.