Doctoral Degrees (Anatomy)
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Item Pneumatization of the temporal bone, its petromastoid part and related vasculature in a South African population from early childhood to early adulthood: an anatomical and radiological study.(2023) Aladeyelu, Okikioluwa Stephen.; Rennie, Carmen Olivia.; Sibiya, Lindokuhle Andile.; Mbatha, Wonder-boy Eumane.Introduction: The pneumatization of the temporal bone is important in various clinical settings. These include serving as a prognostic factor in middle ear surgeries and acting as a shock absorber in patients sustaining lateral skull trauma. The size and growth rate of its air cell system have been associated with middle-ear pathology. The degree of temporal bone pneumatization is highly relevant when planning temporal bone-related surgeries and has been hypothesized to influence anatomical variations of temporal bone-related vessels. This study aimed to investigate the size of temporal bone pneumatization (air cell volume) with age, the association between temporal bone pneumatization and the morphologies of some temporal bone-related vessels, as well as their morphometrical relationship with ear regions, and to propose a simple and concise classification of the degree of temporal bone pneumatization using reference structures and landmarks. Materials and Methods: A retrospective review of 496 temporal bone computed tomography (CT) images of 248 head and neck/brain CTs of patients from public hospitals in KwaZulu-Natal, South Africa, was conducted. The sample consisted of 133 males and 115 females, 0 to 35 years old (median age 13.0 years) of three population groups (202 South African Black, 28 South African Indian, and 18 South African White). The age range of 0 to 35 years was further divided as follows: 0-2 (infant); 3-5 (young child); 6-9 (middle child); 10-14 (early adolescent); 15-18 (middle adolescent); 19-25 (young adult stage I); 26-35 (young adult stage II). High-resolution CT images with fine slices of ≤ 0.625 mm were analyzed using IntelliSpace Portal (ISP) Version 11.1 viewer software. The volume of temporal bone pneumatization was achieved using three dimensional (3D) volumetric rendering technique. At the same time, the morphologies of the sigmoid sinus, jugular bulb, and internal carotid artery and their morphometrical relationships with ear regions were analyzed using the measuring tools on the ISP. Additionally, an inter-observer assessment was conducted among otologists to classify the degree of temporal bone pneumatization utilizing temporal bone CT images at two levels (landmarks): the malleoincudal junction and the lateral semicircular canal using sigmoid sinus as a reference. Results: Size (volume) of temporal bone pneumatization with age: The volume of temporal bone pneumatization increased significantly (p<0.001) with age up to the adult stage I (19-25 years), followed by a significant decline in young adult stage II (26-35 years). Females showed a significant early increase compared to males. Regarding population groups, Black South Africans (SA) showed a higher increase in volume with age than the SA Whites and Indian population groups. xiv Influence of pneumatization on temporal bone-related vessels: Four degrees of pneumatization (hypo, moderate, good, and hyper) were analyzed. Hyper-pneumatization was observed to be more common. Vascular variants such as high jugular bulb, jugular bulb dehiscence, and internal carotid artery dehiscence were observed and significantly associated (p<0.01) with hyper-pneumatization. Also, as pneumatization increases, sigmoid sinus and jugular bulb distances to ear regions were observed to increase significantly (p<0.01, p<0.05). The sigmoid sinus and its variant shapes were also observed but were not significantly associated with the degrees of pneumatization (right- p= 0.070; left- p= 0.645). Classification of degree of pneumatization: In the survey conducted among cohort otologists, the percentage of participants that correctly rated temporal bone CT images taken at the level of lateral semicircular canal according to their respective degrees of pneumatization was significantly higher (p < 0.05) regardless of their year of experience compared to those that correctly rated corresponding images taken at the level of malleoincudal junction. A 76% positivity in their agreement with the use of sigmoid sinus in evaluating mastoid pneumatization was observed. Discussion and Conclusion: This study concludes that the pneumatization of a healthy temporal bone is expected to show a significant linear increase from infant up until at least the early adult stage I (19-25 years) in the South African population. The high incidence of high JB, JB dehiscence, and internal carotid artery dehiscence, and the increase in distances of sigmoid sinus and JB to ear regions reported in this study population due to increased pneumatization validates temporal bone pneumatization as a factor that influences jugular bulb variants and internal carotid artery dehiscence as well as the distances of sigmoid sinus and jugular bulb to ear regions. The study also concludes that using the lateral semicircular canal as a landmark on axial CT, and evaluating air cells around the sigmoid sinus was suitable in classifying the degree of temporal bone pneumatization into hypo-, moderate, good, and hyper-pneumatization. This study proposes this classification system as an easier and quicker method for clinical applications.Item An anatomical exploration of the extracranial (V1-V3) and intracranial (V4) components of the vertebral arteries in a select KwaZulu-Natal population.(2021) Omotoso, Bukola Rukayat.; Lazarus, Lelika.; Satyapal, Kapil Sewsaran.; Harrichandparsad, Rohen.The risk of injury to the vertebral artery is a significant complication of surgery. The presence of anatomical variation in the course of the vertebral artery increases the likelihood of injury. Due to inadequate understanding of the presence and location of anatomical variations in the morphology and morphometry, the vertebral artery can be injured during surgical intervention. Apart from the vascular injury that can occur during surgical intervention, anatomical variations have implications for some pathologies in the posterior circulation territory. These include aneurysm formation, cerebrovascular disorders, posterior circulatory stroke, and some neurovascular problems. In this retrospective observational study, we investigated the anatomical features of the extracranial (V1-V3) and intracranial (V4) components of the vertebral arteries in a South African population. The study is an observational, retrospective chart review of 554 consecutive South African patients (Black, Indian, and White) who had undergone computed tomography angiography (CTA) at Lenmed Ethekwini Hospital and Heart Centre, Durban, South Africa, from January 2009 to September 2019. The vertebral artery exhibited various morphological variations in its course. We report the incidence of variant origin of the left vertebral artery (6.9%). The level of entry into the transverse foramen ranged between C7-C3. We report the incidence of vertebral artery tortuosity at V1, V2: 76.6%, and 32.1%, respectively. We observed fenestration at V3 (0.18%) and V4 (0.4%) segments. We registered the incidence of the persistent first intersegmental artery (1.1%), extradural PICA origin (2.8%), atresia (6.7%), and hypoplastic terminal vertebral artery (13.2%). Average length and diameter at each vertebral artery segment were registered; we also report on hypoplasia of the vertebral artery. Anatomical variations of the vertebral artery are common in the South African population studied in the present study. Imaging of the complete segments of the vertebral artery from the origin to the point of convergence to form the basilar artery may be necessary to decide a treatment strategy for interventions in the vicinity of the vertebral artery. Understanding the patterns of anatomical variations of the vertebral arteries will contribute significantly to the diagnosis of various diseases in the posterior circulatory territory. The average diameter was significantly larger on the left in all the racial groups, but there were no significant gender differences. We registered a left dominance pattern in all the segments (V1-V4). Iqoqa Ingozi yokulimala emithanjeni yomgogodla iyinkinga enzima kakhulu yokuhlinzwa. Ukuba khona kokwehlukahlukana kokwakheka komzimba ekuhambeni komthambo womgogodla kwandisa amathuba okulimala. Ngenxa yokuqonda okunganele kokukhona kanye nendawo yokwehlukahlukana kwesakhikwo somzimba ekwakhekeni nokulinganisa umumo, umthambo womgogodla ungalimala ngesikhathi sokuhlinzwa. Ngaphandle kokulimala kwemithambo yegazi okungenzeka ngesikhathi sokuhlinzwa, ukuhlukahlukana kwemithamdo yomgogodla kunomthelela ngezinye izimbangela ngokuthola umsuka wesifo ngokuhamba kwegazi emigudwini. Lokhu kubandakanya ukwakheka kokuvuvukala komthambo, ukuphazamiseka kokuhamba kwegazi engqondweni, ukushaywa yisifo sohlangothi, nezinye izinkinga ngezinzwa nemithambo. Kulolu cwaningo lokubheka ngokuqhathanisa abanesifo nabangenaso, sibheke ukwakheka komzimba kwamathambo ekhanda ngaphandle (V1-V3) kanye nokwakheka kwawo ngaphakathi (V4) nezingxenye zemithambo yomgogodla emphakathini waseNingizimu Afrikha. Ucwaningo lungukuzibonela ngqo, ukuqhathanisa ngokubuyekeza amashadi eziguli zaseNingizimu Afrikha angama-554 ngokulandelana (abaNsundu, amaNdiya, nabaMhlophe) abafakwe emshinini bahlolwa wonke umzimba ngekhompuyutha ukubona okusemithanjeni (isibonathambomzimba) (CTA) esibhedlela i-Lenmed Ethekwini neSikhungo seNhliziyo, eThekwini, eNingizimu Afrikha, kusukela kuMasingana wowezi-2009 kuya kuMandulo wowezi-2019. Umthambo womgogodla ukhombisa ukwehlukahluka kwesakhiwo ekuthubelezeni kwawo. Sibika isehlakalo semvelaphi esehlukile somthambo womgogodla kwesokunxele (6.9%). Izinga lokungena esikhaleni esiphakathi komthambo womgogodla laliphakathi kwe-C7 ne-C3. Sibika isehlakalo esihambisana nokuguga komthambo womgogodla nomfutho wegazi okulinganiselwa phakathi kuka-V1, V2: 76.6% no-32.1%, ngokulandelana. Sibone ukuhlinzwa kwesakhiwo sendlebe ngaphakathi kwezingxenye ezingu-V3 (0.18%) nezingu-V4 (0.4%). Sabhalisa izehlakalo zomthambo wokuqala ngezingxenye ezilokhu zikhona ngo-1.1%, imvelaphi ye-PICA yamathambo ekhanda (2.8%), isicubu esingenayo embotsheni ngokwemvelo (6.7%), nokungakhuli kwesitho ngokuphelele (13.2%). Isilinganiso sobude nobubanzi engxenyeni ngayinye yomthambo womgogodla yabhaliswa; siphinde sibike ngokungasebenzi ngokwejwayelekile komthambo womgogoda. Ukwehlukahlukana kokwakheka komthambo womgogodla kuvamile kubantu baseNingizimu Afrikha ocwaningweni lwamanje. Ukufanekisa kwezingxenye eziphelele zomthambo womgogodla lapho zihlangana khona ukwenza umthambo ophakathi nendawo ekhanda kungadingakala ukunquma ngamasu okwelapha ngokungenelela endaweni eseduze nomthambo womgogodla. Ukuqonda ukuphiceka kwesakhiwo esahlukahlukene semithambo yomgogodla kuzodlala indima ebalulekile ekuhlonzeni izifo ezahlukahlukene ekuhlinzekweni kokuhamba kwegazi. Isilinganiso sobubanzi besisikhulu kakhulu kwesokunxele kuwo wonke amaqembu ezinhlanga, kodwa kwakungekho mehluko obalulekile phakathi kobulili. Sibhalise indlelakwenza ebihamba phambili kuzo zonke izingxenye ebe ngu-V1-V4.Item Anatomical classification of Tessier craniofacial clefts number 3 and number 4 in a South African population.(2019) Omodan, Abiola Olugbenga.; Madaree, Anil.; Lazarus, Lelika.; Pillay, Pamela.; Satyapal, Kapil Sewsaran.The craniofacial clefts are rare defects of the face with an incidence of 1.43 to 4.85 per 100,000 live births. In 2016, WHO reported a death rate of 303,000 new-borns before 4 weeks of age due to congenital anomalies of which craniofacial clefts are one. Surviving the defect is associated with long term disabilities which impacts the individual, families, the healthcare system and society. How much we know about these clefts is seriously hampered by the rarity and the variations of these defects, so much so, that its treatment and communication amongst researchers is affected. The understanding of the skeletal defects occurring in the clefts has long been postulated as a key to any successive reconstruction of the face. This study aimed to reveal the extent of our understanding of these clefts, document the anatomical basis for the craniofacial cleft number 3 and number 4 and generating a sub-classification based on this and also document the clinical presentation as well as associated clefts of these craniofacial clefts in our select South African population. The methods used to achieve these included conducting a scoping review of the literature on patients with Tessier cleft number 3 and number 4 using relevant identified studies from 1976 sourced from PubMed, Medline, EBSCOhost, Google Scholar and the Cochrane libraries. The result of the study was reported using the Preferred Reporting Items for Systematic and Meta-analyses (PRISMA). Likewise, CT scans of patients who had been treated for Tessier clefts number 3 and 4 at Inkosi Albert Luthuli Central Hospital in Durban South Africa between 2003 and 2017 were analysed. Measurements of the expected defects in each cleft were taken and compared with the unaffected side as reference points. Emerging patterns of their analysis were then used to generate a sub-classification for these clefts. Lastly the records of 8 patients who had been treated for either Tessier cleft number 3 or number 4 were reviewed and compared with 9 studies sourced from the literature. In addition to the defects recorded, associated clefts and other congenital malformations were also documented, and findings were compared. The scoping review had 33 studies that met the inclusion criteria. The majority were conducted in middle income countries (54.5%) while none were recorded in low income countries. Only 12.1% of the included studies reported on anthropometry. In understanding the skeletal defects, the presence of an alveolar cleft, the emerging patterns of comparison of the measurements of the maxilla and the orbits of the cleft side and the non-cleft side as well as absence of the bone were used to arrive at a sub-classification system using (a), (b). (c), (M+ O+), (M- O-), and (0). Clinical presentation of the patients who had been treated as cases of Tessier cleft number 3 and number 4 were compared to the reviewed literature and the different parameters were documented. In addition, associated clefts were also recorded, and this study found that the association pattern noted for Tessier cleft number 4 did not conform to its traditional counterpart. In conclusion, this study found that the knowledge of Tessier clefts number 3 and number 4 exist albeit not fully documented. Also, the study proposed a sub-classification for Tessier clefts number 3 and number 4 that will allow physicians to anticipate the extent and form of skeletal defect present before even seeing the patient. Lastly, it was concluded that however variable these clefts appear; they have a similar presentation worldwide and also that associated clefts do not conform to the original Tessier classification system.Item Effects of momordica charantia on the kidney following antiretroviral therapy in male diabetic and non-diabetic animal model.(2019) Offor, Ugochukwu.; Azu, Onyemaechi Okpara.; Naidu, Edwin Coleridge Stephen.Introduction Management of HIV/AIDS has been successful with the use of antiretroviral therapy (ART). Consequently, the introduction of highly active antiretroviral therapy (HAART) has further increased the life expectancy of people living with HIV/AIDS and this has become a standard regimen in clinical practice. However, discordant views have been reported regarding its effects on the kidney; with a dearth of literature on the impact of HAART in a diabetic comorbid state on the renal morphology and the possible role of plant-based adjuvant. This study investigated the effect of mormodica charantia (M. charantia) on the kidney following HAART regimen (triplavar) and its impact in diabetic nephropathy (DN) in streptozotocin (STZ) induced diabetic rats. Materials and Methods 78 adult male Sprague-Dawley rats were divided into non-diabetic and diabetic groups. Rat models of diabetes were successfully established by intraperitoneal injection of STZ (45 mg/kg body weight). Animals were administered an adjuvant treatment of M. charantia and HAART regimen (triplavar) according to protocols. On the 10th week, animals were euthanized with an overdose of halothane and kidney tissues were harvested and processed for light microscopy and transmission electron microscopy (TEM). Blood samples were obtained via cardiac puncture and centrifuged to collect the serums for biochemical analysis. Urine samples were collected at 3weeks interval during the 10 weeks experimental period for analysis of renal function test. Body weight and blood glucose levels (BGL) were measured once a week during the 10 weeks treatment. Results In the non-diabetic group, HAART alone treated rats showed renal dysfunction which were characterized by raised levels of blood urea nitrogen (BUN) and serum creatinine (Scr), microalbuminuria and gross electrolyte disturbances (Sodium and Potassium) as well as urea retention. Also, levels of oxidative stress (superoxide dismutase-SOD, catalase-CAT and glutathione peroxidase-GPx) were significantly decreased in these groups together with an increased levels of thiobarbituric acid reactive substances (TBARS) resulting in free radical formation via auto-oxidation. More so, the histopathological results displayed severe glomerular capillary abnormalities with inflammatory cellular infiltrations. This correlated with TEM analysis that showed swollen mitochondrial in the endothelium and thickness of the basement membrane with overexpression of extracellular matrix. Furthermore, there were upregulation of circulating neutrophil gelatinase associated lipocalin (NGAL), kidney injury molecule 1 (KIM-1) and tumor necrosis factor-alpha (TNF-α) following HAART alone treatment. In the diabetic groups consistent raised levels of blood glucose which remained peaked from the 5th week of experiment were seen in the diabetic control and HAART treated group. There were increased levels of both BUN and Scr. Renal function test showed leakage of albumin, retention of renal electrolytes (sodium and potassium) and high concentration of urea in the urine of diabetic control and HAART treated group. Activities of antioxidative enzymes (SOD, CAT) and levels of GSH were markedly decreased with an increased level of Malondiadehyde (MDA). Significant (p<0.05) upregulation of the gene expression profiles (NGAL, KIM-1 and TNF- α) were also seen. Qualitative light microscopic result using hematoxylin and eosin (H and E) stains showed glomerular capillary abnormalities and tubular epithelial damage. These findings correlated with other special stains (PAS and MT) which showed high proportion of glycogen, glycoproteins as well as mild deposition of collagen fibers and hyaline substances respectively. TEM analysis displayed an abnormally increased thickness of basement membrane which reflects the existence of endothelial damage (diabetic control). By contrast, following adjuvant treatment with M. charantia, (low and high dose) these abnormalities were significantly reduced thus suggesting a protective effect of M. charantia on the kidney. Conclusion M. charantia extract administration improved blood glucose levels, maintained renal electrolytes (Sodium and Potassium), reinstated renal function (BUN and Scr) restored histoarchitectural and ultrastructural patterns and prevented DN development in an STZ-induced diabetic rat model. Keywords: HAART, Nephrotoxicity, Diabetic nephropathy, TEM, M. charantia, Sprague-Dawley rats, HistoarchitetureItem Investigating the effects of Cinnamomum-cassia nanoparticle conjugate on the Histomorphology of the kidney in type 2 diabetic rats.(2019) Kouame, Koffi.; Azu, Onyemaechi Okpara.; Naidu, Edwin Coleridge Stephen.; Peter, Aniekan Imu.Introduction Diabetic nephropathy remains one of the biggest complications of diabetes. The incidence is increasing and more patients are experiencing progressive kidney failure due to lack of hyperefficient treatment. This study investigated the antidiabetic activity of Cinnamomum cassia silver nanoparticles (AgNPs) [(CcAgNPs)] and its effects on the kidneys of Sprague-Dawley rats induced with type 2 diabetes following administration of Streptozotozin. Materials and methods Adult healthy, pathogen-free male Sprague-Dawley rats, of a total number of 65 (N=65), weighing 250.0 ± 20 g were divided into 10 groups. Groups A-E (positive controls) consists of 30 rats, with 6 rats per group and the experimental groups F-J, consists of 35 rats, with 7 animals per group. Diabetes was induced in animals using Streptozotocin 60 mg/kg administered intraperitoneally. The animals were subjected to various treatments with Cc (100 mg/kg and 200 mg/kg) and CcAgNPs (5 mg/kg and 10 mg/kg). The treatments were administered orally using orogastric gavage and administration was carried out daily following treatment protocol for 56 days. The selected protocol for the experiment was officially approved by the Animal Ethics Committee (protocol reference number: AREC/74/016D). Cinnamomum cassia Silver Nanoparticles (CcAgNPs) was synthesized using the green option and characterized using UV (ultraviolet)–TEM (Transmission electron microscopy)-FTIR (Fourier-transform infrared spectroscopy) –XRD (X-ray powder diffraction), prior to administration. The animals were sacrificed on day 56. Blood and urine samples were collected for biochemical analysis. The kidneys were examined for histopathological changes using Hematoxylin and Eosin (H&E), periodic acid Schiff and Masson’s trichrome staining. Transmission Electron Microscope (TEM) and Stereological studies were carried out as well. Results Urinalysis showed extensive protein and albumin deposits in the urine. Ketones and nitrites levels which are markers of renal function were significantly lower (p< 0.05) in groups treated with CcAgNPs compared to negative controls. Urea and creatinine were also significantly (p < 0.05) reduced in treated groups compared to negative controls. The levels of reduced glutathione (GSH) was significantly different across all groups (p < 0.05). Serum Malondialdehyde (MDA) concentrations were significantly (p < 0.05) lower in CcAgNPs compared to controls. Liver enzymes (alanine aminotransferase) ALT was reduced significantly in groups treated with a low dose of CcAgNPs compared to negative controls. In the group treated with high dose (10 mg/kg) of CcAgNPs, (Aspartate transaminase) AST levels were significantly lower (p < 0.05), compared to the group treated with Cc (Cinnamomum cassia) and to the negative control. Stereological studies showed significantly decreased (p < 0.05) number of glomeruli and tubules in groups treated with Cc and CcAgNPs, compared to the negative control. Transmission Electron Microscope (TEM) revealed the thickness of glomerular basement membrane, in experimental groups, compared to positive controls. Histopathology of renal tissue showed severe glomerular distortion, tubular lesions with H & E and thickening of the basement membrane; pyknotic nuclei and vacuolization with PAS and MT, in the untreated negative control group. Positive controls showed regular glomeruli with normal Bowman’s capsular space, normal basement membrane and regular capillary network compared to negative controls. The degree of histopathological changes in the glomeruli and tubules appear to be dose-dependent. Conclusion Diabetes negatively alters the cytoarchitecture and biochemistry of the kidneys of Sprague-Dawley rats while Cinnamomum cassia Silver Nanoparticles have the potential to ameliorate these changes. The possible pathway involved CcAgNPs may provoke the release of insulin-like, as well as the thioredoxin (Trx), which is one of the central antioxidants that can alleviate renal injuries in diabetic nephropathy. Keywords: Cinnamomum cassia; silver nanoparticles; diabetes; histomorphologyItem Testicular morphological and biochemical perturbations in experimental animals under antiretroviral therapy and the role of Naringenin, a bioactive flavonoid.(2018) Adana, Misturah Yetunde.; Azu, Onyemaechi Okpara.; Naidu, Edwin Coleridge Stephen.Declining male fertility is one of the neglected concerns of people living with HIV/AIDS in spite of a dual outlook of a social and a health dilemma. This issue of infertility is particularly relevant as majority of affected individuals are in their reproductive years. This thesis examines the impacts of the Fixed Dose Combination (FDC) of Highly Active Antiretroviral Therapy (HAART) Tenofovir/ Emtricitabine and Efavirenz (TDF/FTC/EFV) on the male reproductive capacity. It also explores the protective potentials of a bioactive flavonoid, Naringenin in testicular perturbations. The study was motivated by two major research questions namely: (1) what are the impacts of the recently approved first line antiretroviral therapy for adults FDC, TDF/FTC/EFV on the testes? (2) What is the role of Naringenin in alleviating testicular perturbations induced by HAART? Previous studies point to the negative impacts of the older generation of FDC of HAART on the semen quality and histomorphometry of the testes following a long-term use. The study addresses both the long-term and short-term use of antiretroviral drugs as observed in pre-exposure prophylaxis (PrEP) and post exposure prophylaxis (PEP). The research assesses the impacts of the drugs on the reproductive capability as well. Findings from this study support the argument that the negative effects of the drugs were consequent upon both the short-term and long-term use. To illustrate this hypothesis, the study was conducted in two distinct phases. The first phase which lasted a total of 28 days considered the duration of PEP or PrEP. The second phase which lasted a total of ten weeks captured all the stages of spermatogenesis in rats. In this phase male Sprague Dawley rats were exposed to fertile females after the treatments. The study thus advances an understanding of the mechanism of HAART-induced testicular injury. A therapeutic dose of TDF/FTC/EFV adjusted for animal weight was aministered on a total of 48 animals randomly divided into 6 equal groups each with a different treatment as follows; Group A: Control (Distilled water); Group B: HAART (TDF/FTC/EFV), Group C: Naringenin, 40 mg/kg; Group D: Naringenin, 80 mg/kg; Group E: HAART + Naringenin, 40 mg/kg; Group F: HAART+ Naringenin, 80 mg/kg. At the end of each phase, harvested testes were subjected to histomorphometry and ultrastructural analysis. The caudal epididymis was assessed for semen parameters and sperm mitochondrial DNA (mtDNA) fragmentation. Biochemical parameters such as serum levels of reproductive hormones (Luteinizing hormone and Testosterone) and intratesticular antioxidant enzyme activities were assayed. Contrary to prior beliefs, this research reveals that the immediate effects following short-term use of HAART are far more deleterious. This finding is consequent upon the significant drop in the sperm count (p˂0.001) and sperms with normal morphology (p˂0.001) compared to (p˂0.01) in the long-term. Histomorphometric analysis also revealed a significantly shrunken seminiferous tubule following a short-term use. These outcomes were associated with an increase in the mtDNA fragmentation in group B when compared to control (p˂0.05). Naringenin reversed abnormalities in groups E and F, displaying better semen parameters in both count and motility. Serum levels of testosterone were altered in both phases. The overall effects of all these changes were observed in the pregnancy rate which reduced in group B when compared to all the other groups. This study established that HAART has deleterious effects on the testicular microanatomy and function. These effects may impact on steroidogenesis and ultimately spermatogenesis. It consequently impairs fertility while Naringenin promises to be a potential complimentary adjuvant especially in the short term therapies. Keywords: HAART, semen parameters, reproductive hormones, testicular ultrastructure, 3 beta hydroxysteroid dehydrogenase.Item A clinically applied anatomical study of the coronary arteries in the South African population.(2003) Lachman, Nirusha.; Satyapal, Kapil Sewsaran.; Acland, Robert D.Interest in the anatomy of the coronary arteries dates as far back as the early 1500's, at a time when anatomical inquiry was being cautiously aroused. Whilst the later 1700's encouraged academic domination of anatomical study, significant documentation of the coronary arteries was only been established by the late 1800's to early 1900's. There is no doubt that this topic continues to remain dynamic, favoured for its value in applied clinical research. Indeed, technological advancement in the 21 st century has transformed modem day anatomy into more than just a simple descriptive exercise. Whether to update standard literature, create ethnically specific banks of anatomical data, abate technical difficulties associated with coronary artery surgery or provide exciting interventional possibilities for clinicians, revisiting the anatomy of the coronary arteries is clearly warranted. The objective of this investigation was to review the anatomy of the coronary arteries using a clinical approach in order to investigate the morphologic presentation of these vessels within the South African population. On a more clinically universal level, this study aimed to elucidate two focal areas of anatomical interest: extra-cardiac collaterals and myocardial bridges. The investigation was conducted by means of micro-dissection, angiography, histology and scientific evaluation. A total of 323 sets of coronary arterial patterns consisting of patient angiograms (n=212) and cadaveric dissections (n=95) were studied. Specimens were harvested at post-mortem and angiograms and surgical reports were obtained from clinical centers within KwaZulu-Natal. Results of this study confIrmed the standard anatomical description of the coronary arteries as documented. Within the South African population, the ramus marginalis artery was found to be present in 13.3% (Females: 10.7%; Males: 5.6% and Blacks: 18.0%; Indians: 6.6%; Whites: 1.4%). The LAD and LCX arteries arose from independent aortic ostia in 14.5%, (Females: 7.5%; Males: 15% and Blacks: 6.5%; Indians 50%; Whites: 35%). Right dominance was observed most frequently in 85.9% (Blacks: 82.3%; Whites: 83.6% and Indians: 86.4% and Males: 82.6%; Females: 89.2%). A bifId LAD artery was noted in 52%, (Females: 6.2%; Males: 8.7% and Blacks: 17.6%; Indians: 6.3 %; Whites: 4.5 %). In 27.7%, (Females: 24.0%; Males: 28.8% and Blacks: 29.5%; Indians: ·50%; Whites: 20%) the LCX artery failed to continue along the atrioventricular groove. The conus artery arose from a high position off the RCA in 19.2%, (Females: 16%; Males: 21% and Blacks: 19.7%; Indians: 100%; Whites: 10%); and from an independent ostium in 3.61%, (Females: 4.0%; Males: 3.8% and Blacks: 4.9% only). The LCA measured 0.82cm (0.27-2.4cm), (Females: 0.84cm, Males: 0.96cm and Blacks: 0.88cm; Indians: 0.53 cm; Whites: 0.78cm). Myocardial bridges were recorded on the RCA in 2.5% and on the LAD in 50.6%. The bridge pattern depicted myocardial loops to complete arterial investment and ranged in length from 3.0 to 20.02 mm. Scientiftc evaluation of the intramural LAD indicated positive correlation between a straight appearance ofthe LAD on angiogram and a deep myocardial position upon surgical observation (mean "tortuosity index" = 1.147 [1.373-1.045] where 1= baseline for straightness). Results were confIrmed in the correlated cadaveric investigation. Extra-coronary collaterals were observed in 100% (n=9). The arterial pattern consisted of 1 to 2 main stems with secondary anastomotic branches. The average external diameter was measured to be 0.6mm (OA-0.7mm), length 52.5mm (1883mm) with at least 5 secondary branches (3-9) of external diameter O.3mm (0.20.5mm). Results of the histopathological investigation (n=20) indicated the presence of atherosclerotic disease within the intramural LAD artery segment (15%). A 60% incidence was recorded in the pre-mural segment and 25% incidence in the post-mural arterial segments. When analysed in terms of severity, the intramural segment reflected only mild signs of intimal alteration. Although not statistically significant, mean values for coronary artery size differed between sexes. The findings were similar when evaluated in terms of the coronary artery anomalies studied. There were signifIcant differences between ethnic groups in terms of the length of the LCA. Mean values showed that Indians had the shortest LCA's when compared with Blacks and Whites. The highest incidence of the ramus marginalis branch was recorded amongst Blacks. Separate origin of the LCX and LAD was highest amongst Indians and high in comparison to reports documented in other countries. A high origin ofthe conus artery was found to be dominant amongst Blacks. A low incidence of separate origin of the conus from the aorta was recorded in the South African population. These findings are significantly lower than that reported in the literature. A right dominant system has the highest occurrence within this population. Statistical evaluation confirmed that neither sex, ethnicity, age nor height influenced dominance in a coronary arterial pattern. The presence and description of the bifid LAD has been recorded. Its occurrence is highest amongst Blacks. The anomalous path of the LCX has been documented and described. The significantly high occurrence of this disposition of the LCX within the South African population appears to be the highest reported fmd in the literature. In terms of the presence and patterns of myocardial bridges, there are no observable differences between ethnic groups or sex. Results ofthis study confirm a relationship between the straight appearance of the LAD on angiogram and its anatomical presence. Extra coronary collaterals have been successfully investigated and observed. Measurements of vessel dimensions and patterns have been recorded. Results of the histopathological investigation illustrate that the intra-mural LAD artery is relatively protected from vascular disease. It does not however support the theory that in such a sub-myocardial position, the LAD artery is never prone to the damaging effects of atherosclerosis. The "cardio-protective" effect of a muscular bridge, whilst prevalent, is dependant on the thickness and extent ofthe bridge itself The anatomy ofthe coronary arteries has been successfully documented and a bank of data, specific for a South African population has been presented. Significant aspects of coronary arterial patterns have been discussed and interpreted in terms of its clinical relevance. This study presents an original method for the investigation of EeC's using technologically advanced materials and equipment. In addition, a scientific method for confirmation of a "straight" appearance of the LAD artery has been developed in this study. Findings contribute to the bank of diagnostic indicators that may be used to predict myocardial bridges pre-operatively. Through the dissection experience of more than 150 hearts and observation of more than 200 angiograms, this study has been able to contribute to the anatomical description o fthe coronary arteries. In some ways new perspectives were afforded and on the same note, already existing concepts have been verified. The value of this study IS enhanced by the potential clinical impact that such data is envisaged to create.Item Microsatellite instability in colorectal and oesophageal cancer.(1998) Naidoo, Richard.; Chetty, Runjun.The development and progression of carcinogenesis is a major area of interest to many scientists. Numerous factors, including both environmental and genetic have been implicated in the causation of cancer. It is clear that both these factors and others contribute to neoplastic development and progression. Microsatellites are short tandem repeat sequences which are located in the intron segments of the genome. These noncoding sequences range from 2 to 6 base pairs. An increase or decrease in the number of repeat sequences is referred to as microsatellite instability, also referred to as genetic instability. It is thought that microsatellite instability arises as a result of defects in DNA repair process. During DNA synthesis, the DNA repair genes ensure that the correct nucleotide is incorporated into the newly synthesised DNA strand, so when a mismatch base is incorporated, this is promptly removed and replaced with the correct base. However, if the repair system is defective this would give rise to numerous genetic aberrations along that region of the genome. Recently, microsatellite instability and allelic imbalance/loss of heterozygosity have been shown to play an important role in the development of many cancers, especially colorectal cancer (CRC) associated with the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome. This study was undertaken to investigate microsatellite instability and allelic imbalance in colorectal and oesophageal carcinomas in the KwaZulu Natal region of South Africa. The molecular analysis was correlated with clinicopathological data to establish a baseline level on which further studies could be performed. In addition, this study represents the first fluorescent based microsatellite analysis of these two common cancers in South Africa. Normal and tumour DNA was isolated from formalin fIxed paraffin embedded tissue. Fluorescent-based DNA technology using an automated DNA sequencer (Alf Express Automated DNA Sequencer) was employed. CY5 labelled primers for microsatellite markers (DCC, D18S34, D18S58, D3S659, D2S123 and D3S1255) were used. The data was captured and analysed using the Fragment Manager Software. The informativity of the microsatellite markers used in this study ranged from 50% to 71.8%. LOH/AI in the region of the DCC gene in the under 35 years of age CRC was 39.1%, while MSI in this region occurred in 31.25% of cases. The DNA repair gene status in these young patients was as follows: LOH/AI: 31.3% and MSI: 40.4%. In the over 50 years of age CRC, LOH/AI in the 18q region was 28% and MSI was 38%. The DNA repair genes (hMSH2 and hMLH1) in this cohort showed LOH/AI in 24% and MSI also in 24%. As regards oesophageal cancer, LOH/AI in the 18q region was 20.5% and MSI 7.7%. The repair genes showed LOH/AI in 17.9% and MSI in 10.25% of cases. When the molecular events were correlated with clinicopathological features, no statistically significant pattern emerged. However, it must be remembered that relatively small numbers of cases (39) were analysed.In conclusion: • No statistical correlation was found between clinicopathological characteristics and the molecular analysis in either CRC and oesophageal cancer. • LOH/AI and MSI was higher in the under 35 age group. • LOH/AI and MSI in 18q, 2p and 3p in sporadic CRC were similar to other fluorescent-based studies in patients over 50 years of age. • LOH/AI and MSI in 18q, 2p and 3p in oesophageal cancer was similar to studies from other geographical areas. • Finally, fluorescent-based microsatellite PCR and analysis was found to be an objective and efficient technique.