3. Electronic Theses and Dissertations (ETDs) - All submissions
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Item Clinicians' interpretation of ventilation/perfusion (V/Q) lung scan reports(2022) Ismail, AyeshaThe survey of clinicians’ interpretation of Ventilation/Perfusion (V/Q) scan reports will determine which further decisions are taken for the management of patients with suspected pulmonary embolism (PE). This study assessed the referring clinicians’ interpretation of terminology used in V/Q scan reports and how this affected clinical management. Methods: A questionnaire was sent out to 300 clinicians with varying experience levels and working in various different clinical departments. Questions related to terminology used, further management of patients, clinicians’ preferences and areas where imaging reports can be improved. Results: 162 responses were received. Most clinicians (87-94%) understood the terminology recommended by guidelines as intended. A negative V/Q scan despite a high clinical pre-test probability led 33% of clinicians to consider an alternative diagnosis and 59% of clinicians to refer the patient for Computed Tomography Pulmonary Angiography (CTPA). The remaining 8% of respondents would trust their clinical judgement and treat as PE despite a negative V/Q scan. For inconclusive findings on V/Q scan, 72% of respondents would investigate further with CTPA, if there were no contraindications. Only 12% of clinicians would consider therapeutic anticoagulation and repeat V/Q scan in 7-14 days in this situation. There were 16% of clinicians who would trust their clinical judgement and treat as confirmed pulmonary embolism in the case of an inconclusive study. There were 77% of respondents who understood thata negative V/Q scan rules out PE. Conclusion: The majority of respondents understood the intended meaning of the probability of PE described in V/Q reports in our clinical setting. Most clinicians would consider referral for CTPA or an alternative diagnosis in the event of a negative study but a high clinical suspicion for PE. The majority of respondents would refer the patient for CTPA if the V/Q scan was reported as inconclusive. The majority of clinicians understood that a negative V/Q study rules out a diagnosis of PE. Areas where V/Q scans may be improved are important to evaluate as this will facilitate better communication with referring clinicians and ultimately improve patient care.Item Epigenetic inheritance of aberrant DNA methylation signatures as a consequence of chronic paternal alcohol exposure and the effect on embryonic gene expression in mice(2015) Ismail, AyeshaEpigenetic mechanisms regulate gene expression, a particularly important activity during foetal development. DNA methylation contained within promoter and regulatory intergenic regions influence gene activity. In utero alcohol exposure as a result of maternal consumption during pregnancy has been associated with disruption of foetal DNA methylation and gene expression, leading to neurological dysfunction, growth retardation and facial anomalies. While similar phenotypes in offspring have been associated with chronic preconception paternal alcohol exposure, the mechanisms underlying these effects remain largely unexplored. This study aimed to: (1) validate significant changes in sperm DNA methylation in a list of ten candidate genes in male mice chronically exposed for ten weeks to ethanol (n=10) compared to a calorie-equivalent sucrose solution (n=10); (2) validate significant changes in gene expression in candidate genes in the brain, liver and placenta of E16.5 embryos sired by ethanol (n=24) compared to sucrose (n=24) treated male mice; (3) quantify DNA methylation changes in candidate genes in the three embryonic tissues. (4) Lastly, previously generated microarray data were reanalysed using bioinformatics tools to generate a top ranked candidate differentially expressed gene list that was used to identify and analyse biological functions or pathways significantly over represented among these genes using PANTHER and DAVID. This study was unable to provide validation for most of the significant differences observed in the sperm DNA methylome in the original study, most likely because of the low sperm DNA concentration. Significant methylation differences were however observed at individual CpG sites in three candidate genes (Igf1r, Odc1, Depdc1b) in specific tissues of embryos sired by ethanol-exposed males relative to embryos sired by sucrose-treated males. There was concordance in the direction of altered gene expression between the cases and controls using the microarray and real-time PCR approaches for two genes in the brain (Grm7 and Zfp317), three genes in the liver (Igf1r, Vwf and Depdc1b) and one gene in the placenta vii (Vwf). However, none of the candidate genes selected for validation showed statistically significant changes. This may be a result of the modest fold changes observed in the microarray experiment that as shown in many cases, often do not replicate. The remainder of the genes showed no changes in expression in the test embryos relative to the control. The functional enrichment analysis revealed biological processes that were over represented in the brain and liver indicating that they may be more vulnerable to the effects of alcohol, compared to the placenta. Overall, the study could not provide a statistically significant correlation between methylation changes in the sperm that were inherited by the offspring which subsequently dysregulated gene expression in the embryo. However, as trends toward significance and significant DNA methylation changes were observed in the embryonic tissues, this study supports the idea that preconception paternal alcohol exposure can induce epigenetic alterations in a locus and organ specific manner within offspring.