*Electronic Theses and Dissertations (Masters)

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The role of human papilloma virus (HPV) in oropharyngeal squamous cell carcinoma: a clinicopathologic and molecular analysis
(2024) Disenyane, Dineo
Context: Human papillomavirus (HPV) is an established aetiology in a subset of oropharyngeal squamous cell carcinoma (OPSCC). However, literature on the association between HPV and OPSCC in the African context is lacking. Objective: To determine the association of HPV in OPSCC and to correlate it with the clinicopathologic and molecular analysis. Design: A total of 60 OPSCCs were evaluated with HPV in-situ hybridisation (HPV ISH) and immunohistochemistry (IHC) for p16, p53 and Ki67. This was correlated with the site of occurrence of the tumours, the patients' smoking and alcohol usage and microscopic features of tumours (NKSCC;n=30 and KSCC;n=30). Results: HPV DNA was found in 24/60 (40%) cases. HPV16, was positive in 18/60 (30%) cases and HPV6 in 8/60 (13.3%) tumours. Two of the 60 (3.3%) cases were positive for both HPV16 and HPV6. HPV positive (+ve) tumours occurred more in males (n=22; 73%) than females (n=7; 23%); median age: 62.5 years. The primary tumour sites were the tonsil (n=7; 11.6%) and posterior tongue (n=6; 10%). Of the NKSCCs, 11 (36.7%) were HPV16+ve and 8 (26.7%) HPV6+ve. Seven (23.3%) KSCC were HPV16+ve and none (0%) HPV6+ve. Of the 24 HPV+ve tumours, 13 (54.1%) were p16+ve and 14 (58.3%) were p53+ve. Three (12.5%) tumours exhibited the molecular phenotype: p16+ve in > 70% of tumour cells, a low (25%) proliferation index. Conclusion: HPV positive OPSCC is seen more in older male patients. The distinct molecular phenotype, (p16 positive, low p53, high KI67) highlights tumours that are of true viral aetiology. In this study, the low p16 IHC stain sensitivity towards HPV ISH positive tumours infers that p16 is less reliable when used alone as a surrogate marker for HPV associated OPSCC. Therefore, in OPSCC with a high suspicion for HPV and which display a basaloid and non-keratinising morphology, a negative p16 IHC stain should be followed by other molecular techniques such as HPV ISH.
The epidemiology of paediatric burn injuries in 6 Johannesburg, South Africa
(2024) Banga, Agatha Tafadzwa
Background Children remain the most common victim of burns in Sub-Saharan Africa. We investigated the epidemiology of burn injuries of the paediatric patients admitted to the Paediatric Burns Unit (PBU) at the Chris Hani Baragwanath Academic Hospital (CHBAH). Objectives To describe the epidemiology of paediatric burn injury among those admitted to CHBAH. Methods This was a hospital based cross-sectional study, with data collected at the time of admission via an accompanying caregiver questionnaire and via clinical examination of the patient by the admitting doctor. Results A total of 509 patients were admitted to the unit over a 12-month period, with 482 patients included for baseline analysis. 50% of admitted patients were between 15 and 47 months with a median age of 25 months. 205 58% of participants were male. 53% of all admissions had burns above 10% total body surface area and were considered severe burns. The predominant mechanism of injury was scalding (84%), with most overall in the winter season (32%). The most common site of burn was upper limb (75%). 63% of all admissions received 208 first aid. Among those who received first aid,an appropriate first aid method was provided in 74% of the cases. 226 out of 482 participants (47%) provided sociodemographic information. Access to basic amenities such as electricity was high, with most admissions coming from households with access to electricity (91%) and using electricity for cooking (83%). Basic level education was shown by 90% of caregivers holding at least a high school leaving certificate. Migrant caregivers made 19% of the caregivers, which was four times the proportion of foreign nationals counted in the national census. Over three quarters of admissions (79%) were 214 referrals from other centres. Severe burns were associated with thermal mechanism of injury (p<0.01), multiple burn sites (p <0.01), and receiving first aid prior to admission (p=0.01). No sociodemographic factors were associated with increased burn severity. Conclusion Children under two years of age and minority groups are at greatest risk for burn injury and should therefore be targeted for burn injury prevention. Education on appropriate first aid is essential to educate the community. Future research should investigate caregivers of children with burn injury
A comparison of malignant histopathological diagnoses on uterine curettings and hysterectomy specimens
(2024) Ismail, Abdullah
Background. Endometrial carcinoma (EC) is a common gynaecological malignancy in postmenopausal females. Diagnosis is made on endometrial biopsy, where histological subtype and tumour grade are used to predict disease progression and to plan surgical management. Objectives. We aimed to determine the accuracy of preoperative biopsies compared to the final diagnosis on hysterectomy specimens in our department. Methods. This was a retrospective, cross sectional study in which 126 biopsies and corresponding hysterectomy specimens, over a 3-year period, were reviewed. Patient demographics and histological features were recorded and statistically analysed. Results. The most prevalent tumours were endometrioid endometrial carcinoma (EEC) (48.5%), serous carcinomas (25.4%) and carcinosarcomas (16.7%). The majority (66.7%) of tumours were high-grade tumours on biopsy and hysterectomy specimens (58.7%). EECs had a poor sensitivity level (65.12%) compared to other subtypes but had a high specificity rate 90%. There was moderate agreement between biopsy and excision specimen diagnoses. High-grade tumours had a high sensitivity (94.29%) level. Conclusions. Our study showed moderate agreement between histopathological diagnoses on biopsy, and excision specimens. EEC was the most prevalent tumour subtype. There was a high sensitivity (94.29%) level for biopsies of high-grade tumours, concordant with other studies. The sensitivity of low-grade EECs (42-46%) was lower than international studies, likely due to the comparatively low prevalence of EECs in our population. Accurate preoperative tumour subtyping and grading are needed to guide surgical management. It is envisaged that use of a combined histological and molecular tumour classification will better guide patient treatment and allow for reproducible results.
Evaluation of histomorphometric changes in the small intestinal epithelium and paneth cells of male Sprague Dawley rats exposed to alcohol and/or combination anti-retroviral drug (Atripla) therapy (cART)
(2024) Maseko, Zekhethelo Leticia
Significant number of individuals who have HIV/AIDS are also chronic alcohol consumers (Pandrea et al., 2010). Alcohol intake has been found to disrupts ARV drug bioconversion and innate immunity of the gut (Bishehsari et al., 2017), but the exact effects of the combined use of alcohol and/or cARV on small intestinal epithelium and Paneth cells remains unclear. Paneth cells are the main regulator of innate immunity of the gut (Salzman et al., 2010). This study evaluated the histomorphologic appearances of Paneth cells and crypt-villous morphology in small intestine of rats exposed to alcohol and/or combination anti-retroviral drug therapy (cART). The study utilized an experimental study design of 32 adult male Sprague-Dawley rats which were divided into 4 groups and treated with normal saline, alcohol, cART or a combination of alcohol and cART. The animals were sacrificed after 90 days. Segments of small intestine were collected and studied to evaluate the morphometric changes of crypts and villi dimensions in the jejunum and ileum, determine the location of the Paneth cells along the axis of the intestinal crypts of the jejunum and ileum. Furthermore, to examine the histomorphological appearance of Paneth cells including their morphology and amounts of secretory granules, in the jejunum and ileum and examine the histomorphological appearance of stem cells in the crypts of the jejunum and ileum using H&E,special stains and immunohistochemistry. Histomorphometric measurements were done using ImageJ software. Analysis of data was done using STATA SE 15 statistical software. Morphometry and morphological analysis showed significant (p < 0.05) reduction in villous height, villous width, crypt’s depth, intestinal stem cells, increased villous stripping, increased crypt’s width, increased muscular wall thickness, increased number of Paneth cells and staining intensity of Paneth cell granules in alcohol + cART treated group. The increase in number of villi was in all experimental groups and highest following treatment with cART alone or in combination with alcohol. The shortest villi, shallowest crypts and the least number of crypts were seen in ileum of animals that had cART alone. The alcohol alone group had the least number of villi but showed increased collagen content. Paneth cells were noted in the proliferation zone of intestines of animals that had combined treatment (alcohol +cART). Concomitant use of alcohol and cART led to thickening of small intestinal wall, shortening and/or stripping the villi, reduction of crypt depth, appearance of Paneth cells in proliferation zone and a decrease in intestinal stem cells. The structural changes in the small intestine and Paneth cells may adversely affect the regulation of gut innate immunity. These findings are clinically invaluable in the management of HIV patients considering the critical significance of innate immunity amongst HIV patients.
Testing the use of three-dimensional surface rendering and mesh-to-mesh comparisons as a method of pair-matching commingled human skeletal remains
(2024) Pillay, Kamini
When dealing with mass graves, natural disasters, or mass fatalities, forensic anthropology faces a complex scenario that necessitates specific methods for sorting, matching, and identification. The main aim of dealing with commingled human remains is to sort the remains to identify the minimum number of individuals (MNI). Traditional sorting methods, such as visual-pair-matching, articulation, process of elimination, and taphonomy, are welldocumented but subjective and rely heavily on the experience and knowledge of the forensic anthropologist. The study aimed to evaluate the effectiveness three-dimensional surface renderings of bone and the subsequent comparison of mesh-to-mesh values as a more objective and repeatable method for pair-matching commingled human remains. The Structure-from-Motion (SfM) technique was used to create and render 171 three-dimensional mesh model samples using Agisoft Metashape. These models were used to test the effectiveness of a new digital pairmatching method, the mesh-to-mesh value comparison (MVC) method against a South African populated sample. To generate the mesh-to-mesh values, different softwares were used: Viewbox 4.1, which is proprietary and uses a Trimmed Iterative Closest Point (ICP) algorithm to run the program, and Meshlab 2022.12, an open-source software that does not require a license and uses a general ICP algorithm to run the program. Each software was programmed to generate a root mean square value, which was used as the mesh-to-mesh value required for comparison. Analysis was performed using two techniques: LCV (Lowest Common Value) mesh-to-mesh comparison using Microsoft Excel and ROC curve analysis performed using MedCalc. The LCV mesh-to-mesh comparison requires the user to filter, sort, and eliminate values based on observation using specific commands on Microsoft Excel until the lowest agreed upon value is found across left-right and right-left. The ROC curve analysis on MedCalc follows the principle stated by Delong et al. (1988), which works with a scoring system. The closer the threshold value is to the top-left corner of the graph, the higher the accuracy of the test being performed. For the complete cadaveric humeri and femora analysis, both elements performed moderately well with the LCV mesh-to-mesh comparison method, while the ROC curve analysis produced considerably higher results, comparatively. For the complete cadaveric bones, the femur performed better with both softwares when compared to the humerus. Mesh-to-mesh values iv obtained through Meshlab and analysed with the ROC curve method generated significantly higher results and were more adept at correctly identifying and distinguishing differences between matches and non-matches. Differences in mesh-to-mesh values between sexes and different population groups were observed. In the simulated fragmented remains, the distal mesh fragment performed the best with 100% sensitivity for Viewbox, and the shaft performed the best using Meshlab with sensitivity results greater than 79%. For the fragmented remains, the distal mesh fragment and the shaft mesh fragments generated significantly high results when using the values obtained through Viewbox and statistically analysed with the ROC curve method. The mesh-to-mesh value comparison method was applied to a real-world forensic commingled assemblage with high fragmentation and taphonomically altered bones. The Structure-fromMotion technique was effective in capturing distinct details on bones, aiding in 3D modelling. However, the method failed to identify true positive matches in the humeri bone sample, as there were no individuals matched with visual pair matching in the original case. In conclusion, the mesh-to-mesh value comparison method has the potential to improve the accuracy and objectivity of forensic anthropology in handling commingled human remains. By utilizing advanced technologies like SfM, ROC curve analysis, and real-world forensic commingled assemblages, this method can be applied to enhance the accuracy and reliability of forensic anthropological research.
An assessment of developmental anomalies in the thoraco-lumbosacral region of South Africans
(2024) Nchabeleng, Elsie Koketso
Developmental anomalies, typically caused by epigenetic interactions, are very common in the human vertebral column. Many studies have been conducted to assess their prevalence in different populations. Several studies have shown differences in the prevalence and expression of vertebral anomalies among populations and between the sexes. These differences may be related to different geographical areas and the environmental conditions posed by these, socioeconomic status, diets, lifestyles and/or gender roles, to name a few. Therefore, this study aimed at assessing the prevalence and pattern of six developmental anomalies in the thoracolumbosacral regions and their possible associations with vertebral pathologies in South Africans. The study comprised skeletal remains of 902 individuals. The remains were procured from the Raymond A. Dart Collection of Modern Human Skeletons, the Pretoria Bone Collection and the Kirsten Bone Collection. The sample included South African Blacks (SAB) (n=325), South African Coloureds (SAC) (n=286) and South African Whites (SAW) (n=291). The most common vertebral developmental anomaly observed in this study was sacralisation (5.7%), followed by spina bifida occulta (4.5%), spondylolysis (4.5%), L6 (3.1%), and T13 (2.2%). The lowest prevalence was seen for lumbarisation at 1.9%. Overall, developmental anomalies were most prevalent in the SAB sample compared to the SAC or SAW. These anomalies were generally more prevalent in males of the total sample and within the three populations groups of the study. The high prevalence of most developmental anomalies in the SAB sample may be mostly related to the low socio-economic status associated with Black South Africans under the apartheid era. The presence of multiple anomalies was more prevalent in Blacks (44.4%). Blacks also had a higher prevalence for multiple anomalies accompanied by some form of spinal pathology (50%). Whites, on the other hand, had a higher prevalence of a single developmental anomaly accompanied by some form of spinal pathology (50%). In general, males were more prone to developing multiple anomalies accompanied by some form of spinal pathology. There was substantial variation observed with regards to the presentation of the six developmental anomalies in and between the samples under study. Therefore, inter- and intrapopulation differences, as well as sex differences, should be considered when dealing with the above developmental anomalies in biological anthropological and clinical setting
Evaluation of the neuroprotective effects of simvastatin against alcohol-induced damage to the sciatic nerve and the somatosensory barrels in adolescent C57BL/6J mice
(2024) Efuntayo, Alice Adetokunbo
Alcohol is a commonly used and abused drug among adolescents which has an adverse effect on the body’s overall health, especially on the developing brain. It causes neurodevelopmental, neurobehavioral, neurocognitive, and social problems because alcohol exerts its neurodegenerative effects by up-regulating oxidative stress which is responsible for neuronal death. The rising prevalence of alcohol-related diseases and disabilities and the cost to the government necessitates investigation into interventions that could protect the neurons against the damaging effects of alcohol. One drug with antioxidant properties is Simvastatin, a U.S. Food and Drug Administration (FDA) approved drug for lowering blood cholesterol levels. The neuroprotective effects of Simvastatin against alcohol neurotoxicity were evaluated on the sciatic nerves and the somatosensory barrel cortices of adolescent mice. 40 four–week old C57BL/6J male and female mice were administered 20% alcohol (i.p.), 5 or 10 mg/kg Simvastatin orally followed by 20% alcohol (i.p.) or the controls (i.e. 5 mg/kg Simvastatin only or non-treated) consecutively for 28 days. The axonal density, myelin thickness and g-ratio of the sciatic nerves were assessed as well as the sizes of the Posteromedial barrel subfield (PMBSF) barrels. The results confirmed alcohol neurotoxicity on the axonal density and myelination in both sexes. At the same time, Simvastatin was effective against the onset of alcohol nerve damage. For the somatosensory barrels, alcohol did not significantly reduce the mean areas of (I) the PMBSF barrels, (II) the enclosure, or (III) the septal portion in both sexes. However, the barrel-to-barrel comparison revealed alcohol toxicity on specific barrels in specific rows and arcs of the PMBSF barrels. Both concentrations of Simvastatin were also effective against alcohol–induced damage on those specific barrels. These may explain the reasons for the sensory-motor delays that are often seen in alcoholics due to possible delays in the relaying of sensory input and the processing and interpreting of information from the somatosensory cortex. Simvastatin seems to have the ability to protect against the damaging effect of alcohol on the peripheral nerves and the somatosensory cortex and this may be beneficial in reducing the prevalence of alcohol-related diseases or disabilities, especially in adolescents that are prone to abusing alcohol.
A morphometric analysis of the growth of the immature and sub-adult human palate
(2021) Onwochei-Bolum, Nkemakonam Vincent
Postnatal nutrition in humans is associated with advancement in the mode of feeding from the neonatal and infancy period of growth to adulthood. During the neonatal and infancy periods, the palate functions in suckling, tongue manipulation and swallowing, while in adulthood and with dental eruption, the palate participates in both mastication and in the production of sound. It is anticipated that the transition in the role of the palate due to alterations in its function over time will cause morphological changes. Thus, the aim of this study was to analyse alterations in the shape and dimensions of the human palate from birth through the stages of dental eruption to the complete emergence of the permanent dentition in the sub-adult stages of life. Crania from 72 South African individuals were sourced from the Raymond A. Dart Collection of Human Skeletons, School of Anatomical Sciences, Faculty of Health Sciences, University of the Witwatersrand. The sample was divided into three age groups to correspond with the age ranges of the eruption of the deciduous dentition (birth to 5 years of age), mixed dentition (6 to 12 years of age) and the permanent dentition (13 to 20 years of age) respectively. A series of 14 osteological landmarks were digitized across the oral surface of the palate using an Immersion MicroScribe G2 unit. Landmark data were converted to linear distances and the length, width and elevation of the palate were assessed in relation to the state of the dentition. Analysis included both quantitative (linear measurements) and qualitative (wireframes) methods. The length and width of the palate in the permanent dentition group was significantly larger when compared to the mixed and deciduous dentition groups. While elevation of the palatal dome in the permanent dentition group was significantly greater than that of the palate in the mixed dentition group, no further significant differences were observed. Thus, changes in the morphology of the palate appear to be progressive with dental eruption and development across the different states of the dentition. By establishing the nature of the changes in the functional environment of the palate during development and growth, abnormalities in the postnatal development of the palate could be diagnosed.
The association between skeletal lesions and tuberculosis in a South African sample
(2021) Masiu, Rethabile
Tuberculosis is an infectious disease. Skeletal TB is the extra-pulmonary manifestation of Mycobacterium tuberculosis infection and occurs in about 1-5% of all TB cases. The aim of this study was to assess the sensitivity and specificity of skeletal lesions to accurately diagnose TB in a pre-antibiotic South African skeletal sample. For this purpose, 23 skeletal lesions were assessed on 436 skeletons from the Raymond A. Dart Skeletal Collection. These skeletons were divided into three groups: individuals where TB was recorded as cause of death (n=177), individuals where other pulmonary diseases were recorded as cause of death (n=109) and individuals where a variety of diseases, excluding TB and other pulmonary diseases, were recorded as causes of death (n=150). Chi-squared and Fisher’s Exact tests were used to assess differences between groups. The skeletal lesions’ respective sensitivities and specificities were also calculated and compared to a similar study by Dangvard Pedersen et al. (2019a). Lesions on the ventral surface of thoracic and lumbar vertebral bodies were observed significantly more in TB cases than in controls. This lesion type was also found to be the most valuable indicator with a high sensitivity and 55% probability of a true TB diagnosis if observed. An association between skeletal lesions and TB could only be found for rib and vertebral lesions. Distinct differences between this study and the study by Dangvard Pedersen et al. (2019a) indicated that TB-related changes were likely to be observed in a South African skeletal sample even when individuals were not documented to have died of the disease.

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