Masters Degrees (Medicine)

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Evaluation of serological techniques in the diagnosis of active invasive amoebiasis.
(1991) Sathar, Mahomed Aslam.; Simjee, Ahmed Essop.; Bredenkamp, B. L. F.
Abstract available in PDF.
The clinical and biochemical severity of plasmodium falciparum malaria in Natal/KwaZulu.
(1992) Soni, Paresh Nathalal.; Gathiram, Chaiteshwar Vinodh.
Abstract available in PDF.
Autoerotic and assisted sexual asphyxias.
(1993) Book, Robert Gene.; Botha, J. B. C.
Abstract available in PDF.
An immunocytochemical study of the kallikrein-kinin system on the circulating neutrophil.
(1996) Naidoo, Yugenthree.; Bhoola, Keshavlal Daya Narotam.
Inflammation is the normal biological response to tissue injury, and is characterised by the interactive activation of multiple mediators and cell types. One response to tissue injury is the production of pain, not only by direct trauma to sensory fibres, but also through the release of mediators from sensory nerve terminals. One such mediator is kinin which is a vasoactive peptide considered to play a primary role in inflammation by causing constriction of venules, dilation of arterioles, increasing permeability of the capillary membrane, and interacting with sensory nerve terminal transmitters to evoke pain. The kinin forming enzymes (kallikreins) reach inflammation sites either on the surface of migrating neutrophils or by transudation from plasma. The kininogen molecule which contains the kinin moiety, has been localised on the external surface of the neutrophil, and provides the substrate from which kinins can be cleaved through enzymatic action. The cellular actions of kinins are mediated through B2 receptors, which are also located on the external surface of the neutrophils. In addition, the induced effects of kinins are regulated by B1 receptors. The formation of nitric oxide (NO) from arginine released from the kinin C terminus, and receptor membrane signal transduction by nitric oxide following kinin receptor activation is discussed. A molecular response to cell injury is the formation of chemotactic mediators that attract neutrophils to sites of inflammation. The question whether neutrophils contribute to circulating levels of kinins was examined in infections and inflammatory disorders. This novel hypothesis was tested using circulating neutrophils harvested from patients with tuberculosis meningitis and pneumonia. These neutrophils showed a distinct loss of only the kinin moiety from the kininogen molecule located on the external surface. The confocal images of fixed, permeabilised neutrophils provided multi-dimensional constructs, and the intensity of fluorescence reflected the relative amounts of the molecule present in both neutrophils harvested from healthy volunteers as well as patient blood. The immunocytochemical labelling experiments using colloidal gold as markers, confirmed, at the ultrastructural level, the presence or disappearance of the kinin moiety from the kininogen molecule on the neutrophil surface. The cell component of synovial fluid in rheumatoid athritis (RA) consists mainly of neutrophils. This study demonstrates the absence of the kinin moiety from circulating and synovial fluid neutrophils from patients with RA, as well as an increased signal from immunolabelled B2 receptors in synovial fluid neutrophils. These findings support the hypothesis that in RA, kinins are released during the inflammatory response in the joints, and suggests that there is an upregulation of the B2 receptor at the site of inflammation. Neutrophils chemotactically drawn to the site of inflammation become activated to release kinin from the kininogen molecule, and thereafter re-enter the circulation where they were harvested systemically. B2 receptors may be upregulated following activation by kinins or by other mediators present in the inflammatory milieu. Interleukin-1 has been shown to upregulate kinin receptors on human synovial cells. Anti-peptide antibodies to the loops of cloned B1 and B2 receptors have provided powerful probes for the cellular identification of the two kinin receptor families. Mapping of the B2 receptors showed upregulation on the neutrophils gathered from inflamed joints. However, no activation of the Br receptors was observed in normal blood neutrophils as well as those obtained from the different disease states.
Suturing of the faucial pillars and its effect on the pain following tonsillectomy.
(1998) Zieciak, Wojciech.; Williams, Brian Henry Craster.
Abstract available in PDF.
Isolation, identification, immunolocalisation and elucidation of the role of plasma kallikrein in human tissues.
(2000) Cerf, Marlon Eugene.; Raidoo, Deshandra Munsamy.
Introduction: Plasma kallikrein (PK) is a cofactor in blood coagulation and modulates inflammation through the release of bradykinin (BK). Previously it was believed that plasma prekallikrein (PPK), the precursor of PK and a member of the serine protease superfamily, was synthesised exclusively by hepatocytes and secreted into circulation. However, recent studies show that various human tissues contain PPK mRNA. In this study we sought to determine in which human tissues PK is expressed. Methods: Following approval by the Ethics Committee at the University of Natal, tissue samples from the spinal cord, 13 different regions of the brain, 7 different blood vessels and various other organs were collected at autopsy within 24h of death (n =10). Sections were probed using polyclonal antibodies specific for PK. PK concentrations in extracts of these tissues were measured by competitive EllSA. Results: A Western blot analysis demonstrated the monospecificity of the antibody for the PK protein. The presence of immunoreactive PK in cells of the pancreatic islets of Langerhans served as a positive control for each immunolabeling experiment. The hepatocytes, renal distal convoluted tubules and epithelial cells lining the bronchiole and pulmonary alveoli labeled positively for PK. In the gastrointestinal tract tissue, immunoreactive PK was visualised in the acinar cells of the salivary gland, in stromal and glandular duct cells of the oesophagus, and in some chief and glandular cells in the stomach. Some of the above-mentioned tissues contained a few inflammatory cells which stained intensely for PK. Immunoreactive PK was visualised in the endothelial cells and smooth muscle cells of the all the blood vessels examined, except the renal vein. Increased immunolabeling for PK in the endothelial cells, foam cells and macrophages was observed in arteries with atheromatous plaques. In neural tissue immunoreactive PK was observed in neurons, ependymal cells, fibre tracts, and in secretory cells of the anterior pituitary gland. Immunolabeling for PK was visualised in some neurons of the spinal cord and in different brain regions viz. hypothalamus, cerebral cortex, thalamus, brain stem and hippocampus. In sections of the hypothalamus and spinal cord, we observed immunolabeling for PK in ependymal cells lining the third ventricle and central canal respectively. Positive labeling for PK was evident in fibre tracts of the pons, medulla and hippocampus. No immunoreactive PK was visualised in the choroid plexus or cerebellum. High amounts of PK were measured by competitive ELlSA in extracts of the pancreas (12.94 ± 2.04 /-lg/ml), the pons (1.67 ± 1.46 /-lg/ml) and aorta (0.44 ± 0.14 /-lg/ml). The basilar artery (0.09 ± 0.07 /-lg/ml) and spinal cord (0.09 ± 0.04 /-lg/ml) had the least PK concentrations. Discussion and Conclusions: We have shown that the PPK mRNA demonstrated in various human tissues is most likely translated into protein by the immunolocalisation of PK within specific cells in the different tissues examined. The actions of PK within these tissues may be two fold, firstly by its kininogenase activity it may release BK from high molecular weight kininogen, or alternatively, PK may act as a proteolytic enzyme on other proteins. With respect to the latter) PK may be involved in the processing of protein precursors, for example precursors of the digestive enzymes found in saliva and in gastric secretion, insulin precursors in the pancreas, and hormonal precursors in the pituitary gland. The localisation of PK and B1 and B2 kinin receptors in the kidney, lung, stomach, blood vessels and brain suggests that the effects of PK in these tissues are mediated by BK-receptor interaction. These may include the regulation of glucose uptake in the pancreas, water and ion transport in the kidney, and local and systemic blood pressure in the cardiovascular system. The presence of immunoreactive PK in neurons suggests that BK-receptor mediated interaction may regulate neurophysiological processes such as synaptic transmission. Immunolabeling for PK in polymorphonuclear leukocytes observed in some of these tissue sections suggests the potential to mediate the inflammatory process.
The clinical natural history of snakebite victims in Southern Africa.
(2000) Blaylock, Roger.; Robbs, John Vivian.
The author wrote a dissertation for the Mmed Sc degree entitled The Clinical Natural History of Snakebite in Southern Africa, which dealt with the epidemiology of snakebite and the clinico-pathological events in snakebite victims. This thesis is a sequel on the management of snakebite victims. Publications on the overall management of snakebite in the Southern African region that include original scientific research are those of F.W. Fitzsimons (1912), F.W. Fitzsimons (1929) (assisted by V.F.M. Fitzsimons), P.A. Christensen (1955, 1966, 1969) and Christensen & Anderson (1967). Subsequent books, pamphlets and journal articles have rehashed this knowledge or advocated methods of treatment developed in other countries. An example of the latter is the pressure immobilisation prehospital measure advocated for snakebites in Australia (Sutherland et aL, 1979, 1981, 1995), which I regard as benefiting less than 1% of snakebite victims here and being deleterious in most cases. In view of the paucity of research done in Southern African in recent years, many questions remain unanswered, and some strongly held views are without logical or scientific foundation. Most of these questions arose prior to the writing of this thesis, and others arose when the data were analysed. The following are some questions on the management of snakebite that have still have to be addressed. Is vaccination against snakebite possible and practical? Are folk and traditional remedies advantageous or deleterious? How commonly are they used? Immobilisation of the bitten part and the patient is an internationally recognised aid measure, but is this relevant to the Southern African situation? Tourniquet use in the case of necrotising venoms is considered to aggravate or precipitate necrosis. Does immediate active movement following a bite ameliorate or prevent necrosis without increasing mortality? The majority of clinicians recommend antibiotic prophylaxis, but is this necessary for all snakebites, against which bacteria should antibiotics be administered, and what is the source of these bacteria? Should antivenom be administered to all snakebite victims: for species-specific bites, only if envenomation is present, for severe envenomation, or not at all? Acute adverse reactions to South African manufactured snakebite antivenom has been variously recorded as less than 1% (Visser & Chapman 1978) up to 76% (Moran et al., 1998). What is the truth? Is syndromic management of snakebite efficacious or is it essential to identify the particular snake species? Is the present liberal use of fasciotomy necessary? Is there an optimum time to debride necrotic areas and is surgery necessary at all? Is paresis or paralysis due to neurotoxic envenomation always the result of a post-synaptic block? Would such a block respond to neostigmine or prostigmine in a similar way to post-synaptic anaesthetic muscle relaxants? Is heparin of value when procoagulant toxins induce a consumption coagulopathy? Do fibrinstabilising agents or fibrinolytics have a role? Does the management of pregnant snakebite patients differ from that of non-pregnant patients? Is snake venom teratogenic? Does snake venom ophthalmia frequently lead to blindness? Are steroids, NSAIDs and antihistaminics, which are commonly used in the management of snakebite, of proven value? This thesis attempts to answer these questions and more, and comprises six sections. The first section deals with pre-hospital management, the second with infection which may occur at the bite site wound, the third with SAIMR snakebite antivenom, the fourth with the three envenomation syndromes, the fifth with snakebite in pregnancy, venom ophthalmia and other treatment modalities, and the sixth section includes a summary, appendix and references. Unless otherwise stated, the materials and methods of each chapter are based on 336 snakebite victims admitted to Eshowe Hospital, KwaZulu-Natal, from January 1990 - July 1993 and other victims treated by the author, the data of which have been prospectively maintained. This has been an ongoing process up to the present time.
Community acquired pneumonia in HIV and non-HIV infected patients presenting to a teaching hospital in KwaZulu-Natal : aetiology, distribution, and determinants of morbidity and mortality.
(2004) Nyamande, Kennedy.; Lalloo, Umesh Gangaram.
No abstract available.
The effect of angiotensin converting enzyme inhibition on nephropathy associated with human immunodeficiency virus infection.
(2005) Han, Thin Maung.; Naicker, Saraladevi.; Assounga, Alain Guy Honore.
Abstract available in PDF.
Conditions associated with levels of allergens and fungal aerosols in selected homes of selected primary school children in Durban.
(2007) Jafta, Nkosana.
This indoor environment study formed part of the South Durban Health Study (SDHS) that investigated the health effects of exposure to ambient air pollution. Homes of children from seven communities corresponding schools were recruited to participate. This study was designed to determine characteristics in the homes that are associated with higher or lower levels of allergens and fungal aerosols. Homes were inspected using a field tested walkthrough checklist to collect data on home characteristics associated to adverse health effects. The characteristics include dampness, visible mould, type of flooring, type of bedding, type of heating systems, and building type and age. Dust samples for allergen analysis were collected from the bedding and the floor of the sleep area used by the children. Air samples from all rooms in the house were collected on malt extract agar, the media used for identifying and quantifying airborne fungal aerosols. More than 70% of the homes were single units standing on their own, 20% were attached houses (flats or apartments) and the rest (10%) were informal houses. Construction material of the homes comprised of bricks (93%), wood (5%) and other material (2%) such as corrugated iron of which 94% were formally constructed. Dampness signs were observed in 51% of the homes and visible mould growth 13% of them. In all them, at least one characteristic that is hypothetically associated to elevated house dust mite allergens was found. Levels of mould (Asp f 1) allergen and house dust mite (Der p 1 and Der f 1) allergen were comparable to levels found in other parts of the world. Asp f 1 allergen levels ranged between 0.32-1.379g/g and Der p 1 and Der f 1 allergen levels ranged from undetectable to 49.61 and from undetectable to 39.319g/g of dust respectively. Some home characteristics from walkthrough checklist were associated with Asp f 1, Der p1 and Der f 1 allergen levels when simple regression analysis was performed. Asp f 1 was significantly associated with single family home [OR= 0.004 (95%CI 0.004–0.35)] and polyester filled pillows [OR= 0.07 (95%CI 0.01– 0.61)] in logistic regression models. Der p 1 allergen was associated with observed extent of roof dampness [OR= 0.33 (95%CI 0.13–0.81)]. Fungal aerosol mixture consisted of Cladosporium spp. as the predominant genus together with other genera such as Aspergillus, Penicillium and Fusarium were, to a lesser extent, identified in the samples from the homes. Mean concentration of total indoor fungal aerosol of indoor and outdoor were 1108 CFU/m3 and 1298 CFU/m3 respectively. Individual genera of fungi in the childrens sleep area had mean levels of 783 CFU/ m3, 30CFU/ m3, 64CFU/ m3, 48CFU/ m3 and 43 CFU m3 for Cladosporium spp., Aspergillus spp., Penicillium, spp., Fusarium spp. and Rhizopus spp. respectively. Simple regression showed some conditions in the homes to be predictors of higher levels of total fungal aerosols. In a linear regression models, total outdoor fungal levels were a protective effect on total indoor fungal levels [C= 0.542 (95%CI 0.437–0.647)] whilst homes with hard floors had about 25 CFU/m3 [C= 5.235 (95%CI 0.557–9.913)] in the homes were significantly associated. This study showed the need to adapt observational instrument/ checklist/ questionnaire to suit the environment or the study area of interest. As other studies and findings indicated, the best way to assess exposure to biological pollutants indoors needs a combination of two or more methods, i.e. direct and indirect methods.
Human T cell lymphotropic virus 1 associated infective dermatitis in KwaZulu-Natal, South Africa.
(2008) Hlela, Carol.; Mosam, Anisa.
Background Human T cell Lymphotropic Virus Type I (HTLV-I) associated infective dermatitis, first described by Sweet in Jamaican children, is a pattern of eczema characterized by exudation, crusting around the nostrils, ears and scalp with eventual appearance of a generalized fine papular rash. More recently LeGranade and co-workers have proposed major and minor criteria in establishing the diagnosis of HTLV-I associated infective dermatitis (HAID). HTLV-I has been aetiologically linked to Adult T cell leukaemia/lymphoma (ATLL) and tropical spastic paraparesis (TSP). HAID is not only a marker of childhood infection with HTLV-I but may be a harbinger of more serious HTLV-I associated diseases later on in life such as ATLL or TSP. The pathogenesis of HAID is poorly understood so are the histopathological features of this entity. The effects of co-infection with human immunodeficiency virus- 1 (HIV-1) are inconclusive. HAID is described in Sub Saharan Africa, Senegal but no data is published on this entity in Southern Africa, characterizing the clinical, laboratory features and the histopathology of this entity. Aims and Objectives 1) To describe the clinical and histological features of HTLV-I associated infective dermatitis in KZN, South Africa 2) To determine the virological characteristics of HTLV-I in KZN, South Africa 3) To assess for HTLV-I / HIV co-infection Methods This was a prospective study of all patients with HAID who presented to King Edward VIII hospital (KEH), outpatient department over a period of 42 months. These were patients who fulfilled the clinical criteria of HAID. Enrolled patients were subjected to a confirmatory HTLV-I serology testing. Demographic data was obtained from all HTLV-I seropositive patients. Their clinical examination included dermatological, neurological and pathological examination. A blood count, immunoglobulin levels, serum protein electrophoresis measuring albumin levels and globulin fractions were measured. For bacteriological assessment skin swabs were taken from the affected sites with stool samples examined for parasites, ova and cysts. The HIV-1 status together with HIV-1 viral load were determined on those enrolled. The CD4 count, CD8 counts and CD4/CD8 ratio were also calculated. Skin biopsies were taken for histological examination. PCR for HTLV subtyping was performed on a subset of the cohort. Results Demography Of the 60 patients recruited, 33 fulfilled criteria for HAID. The majority of patients fell between age categories of 6 to lOyears. The male to female ratio was 1:1. There were more females in the adult group than there were within the childhood group. All of the patients in our cohort were African. Clinical features The lesions were erythematous, scaly, exudative, and crusted in all cases. The distribution of lesions was as follows: scalp (77.4%), retroauricular areas (71%), the axilla (65%) and paranasal areas (58%) were the sites more commonly affected. Nasal crusting was not a significant feature in this series. Bacteriology Culture was positive for Staphylococcus aureus (S. aureus) in 90%, with streptococcal group of organisms found in 68% of the skin swabs taken from the lesional skin. Haematological Our patients were mildly anaemic as has been shown in previous studies. They had a mean Hb of 11.5g/dl. In 12 of the 14 patients tested, the erythrocyte sedimentation rate (ESR) was elevated. Serum protein electrophoresis and levels of Immunoglobulin A, G and M were raised. The mean CD4 count in the entire group was elevated at 1730 cells/fil, CD8 was 1299 cells/ul Histopathology The major histological findings were as follows: 38% demonstrated a superficial and deep perivascular inflammatory infiltrate, 28% had a superficial and deep perivascular inflammatory infiltrate together with a lichenoid dermatitis, 12.9% had features of superficial and deep inflammatory infiltrate with an interface dermatitis, 6.4% revealed features of seborrhoeic dermatitis. Genotyping Our patients were infected with the strains belonging to the Cosmopolitan, A Subtype (HTLV-Ia). Complications Complications were low in this series with the commonest being scabies in 6(18.1%), corneal opacities in 3(8.6%), 2(6 %) with HAM/TSP. No parasitic worm infestations were isolated. HIV/HTLV-I co-infection Of the 33 patients, 9 (30 %) were co-infected with HIV. The mean viral load in this group was 52 000 copies/ml. Their mean CD4 count was also elevated at 1505cells/^il with a CD8 of 1704 cells/Mi and a CD4/CD8 ratio of 1.15. Discussion Thirty three of the 60 patients enrolled met the diagnosis for HAID according to the established criteria. The mean age in this series was 17 years (range: 8 months-46 years)however; almost a third (30.3%) were children under 12 years, reinforcing the entity as a childhood infective condition. There was an equal male female distribution in the childhood group and a female predominance in the adult group. Clinically patients presented with infected erythematous, scaly lesions mainly on the scalp, neck and post- auricular area. The clinical features were in keeping with other series worldwide. The complication rate was low in our cohort. S. aureus was the predominant organism in both anterior nares and lesional skin. The most common histological pattern was superficial and deep perivascular inflammatory infiltrate. The subtype in our series was the Cosmopolitan Subtype A (HTLV-Ia) as opposed to subtype B in Japan. We share with Brazil a common subtype. A subset of our patients (30%) was co-infected with HIV. The CD4 cell count in this subgroup was lower than the entire group but this was not statistically significant. The histological patterns found in this subgroup infected with HIV were similar to the rest of the group except for a more intense eosinophilic infiltrate in these skin biopsy specimens. Conclusion HTLV-I associated infective dermatitis is distinct entity which affects the African population of KwaZulu Natal, South Africa. It is predominantly a disease of childhood with an equal female to male ratio in children. The clinical features are an exudative, erythematous scaly rash most commonly found involving the scalp, axillae, paranasal and retroauricular areas. HTLV-I positivity is essential for the diagnosis; the Cosmopolitan Subtype A is commonest in South Africa. The commonest histological pattern is a superficial and deep perivascular infiltrate in 38%. A subset, 30%, was co-infected with HIV.
Assessment of the immune response in kidney transplant patients.
(2009) Omarjee, Saleha.; Assounga, Alain Guy Honore.
Background: Management of a transplant recipient involves the use of multiple immunosuppressant drugs. Currently there is no test that reflects the overall immune status of the patient. This results in under or over suppression of the immune system and consequently increases in morbidity and mortality rates. Evaluation of the proliferative response of PBMC's to a mitogen PHA by measurement of intracellular ATP was evaluated as a tool to assess the immune response in kidney transplant patients. Method: PBMC's were separated from the blood samples of healthy controls and kidney transplant patients on cyclosporine, sirolimus, and tacrolimus based regimens by density gradient centrifugation, cells were counted and incubated overnight with and without PHA. The luciferin-Iuciferase enzyme reaction which induces bioluminescence and the Turner Biosystem luminometer were used to measure intracellular ATP levels in relative light units (RLU). An A TP standard curve was generated for each test. Results: The ATP (nglml) levels measured in the transplant recipients were lower and statistically significantly different (p< 0.0001) than the healthy controls. No statistically significant difference was measured between the cycIosporine and sirolimus drug groups. Patients on tacrolimus gave a statistically significant (p501 nglml ATP). Conclusion: Future studies to determine the predictive value of the A TP assay in directing immunosuppressive therapy are required. The assay described in this study is simple, sensitive and rapid and has possible application in immunological monitoring in a variety of conditions that affects the immune system. Keywords: kidney transplantation, immunosuppression, bioluminescence, lymphocyte, Adenosine Triphosphate (A TP), Phytohemmagglutinin (PHA)
Regulation of tumour-angiogenesis by protease inhibitors and receptor antagonists.
(2012) Naidu, Naressa.; Naidoo, Strinivasen.; Botha, Julia Hilary.
Introduction Angiogenesis, the growth of new blood vessels from the pre-existing vasculature, is a pre-requisite for tumour growth and metastasis. Tumour-angiogenesis is regulated by various pro- and anti-angiogenic factors released by both endothelial and tumour cells, as well as by the micro-environment. Numerous studies have implicated various systems in the acquisition of the angiogenic phenotype. The present study sought to investigate the role of the kallikrein-kinin system (KKS) in tumour-angiogenesis. The kallikreins consist of two serine proteases, plasma and tissue kallikrein (TK), involved in the release of kinin peptides by enzymatic cleavage of kininogens. Stimulation of the cognate bradykinin receptors (BKR), B1R and B2R, mediates the mitogenic and vasoactive properties of kinins. In addition, TK activates matrix metallo-proteinases (MMPs) involved in extracellular matrix (ECM) degradation. The expression profiles of TK and kinins have been found to be dys-regulated in numerous human cancers, and several studies have demonstrated the involvement of the KKS in growth and metastasis of prostate tumours. Further, previous in vitro models in our laboratory have established an association between the KKS and prostate tumour-angiogenesis. In those studies it was postulated that the up-regulated TK (produced by endothelial and tumour cells) stimulated endothelial cell proliferation. Thus, the aim of the present study was to define the effects of the KKS and seek a direct correlation with angiogenesis using in vitro models with tumour conditioned medium (CM), kinin receptor agonists and antagonists. Methods Ethical approval for this project was granted by the Biomedical Research Ethics Committee, University of KwaZulu-Natal (reference number BE152/08). Micro-vascular endothelial cells represent a suitable in vitro angiogenic model and dermal micro-vascular endothelial cells (dMVECs) were obtained commercially for this purpose. The tumour model used in this study was an immortalised prostate cancer (DU145) cell line. The CM model involves the treatment of one cell line with the metabolites of another. In the angiogenic model, dMVECs were exposed to increasing concentrations of DU145 CM. Stimulation was further augmented with BKR agonists. Specific BKR antagonists were used to test the specificity of stimulation. In addition, vascular endothelial growth factor (VEGF) was tested as a positive proliferation control. The potential of these agents to induce proliferation and migration was determined using the 3-[4,5 dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assay and a modified Boyden chamber assay, respectively. Previous studies investigating the pro-angiogenic effects of CM differed, in many respects, in terms of their models and methodologies. In an attempt to fully explore the pro-mitogenic effects of CM on endothelial cells, various modifications, as well as alternate endothelial and tumour cell types, were employed in the present study. The mitogenic and migratory effect of BKR agonists and antagonists on DU145 cells was also assessed. Further, the tumour model was expanded to investigate the autocrine potential of the KKS, by investigating the effect of DU145 CM on DU145 migration. Results In the angiogenic model, although the addition of DU145 CM elicited a statistically significant increase in micro-vascular endothelial cell proliferation, this increase was very small (<10%) and not dose-dependent. Pre-incubation of dMVECs with a B1R or B2R antagonist did not influence this small effect of CM on proliferation. In addition, neither B1R nor B2R agonists, at any concentration, produced any significant proliferative effect on endothelial cells. In contrast to these findings VEGF, a well-known mitogen, was able to stimulate proliferation of dMVECs. Migration assays revealed that DU145 CM failed to stimulate endothelial cell motility. Further, neither BKR agonist displayed any chemo-attractant potential in those assays. The most important finding was in the tumour model, where stimulation with a B1R agonist significantly enhanced proliferation and especially migration of DU145 cells. In addition, pre-treatment with a B1R antagonist abolished both these effects. B2R agonists could not produce the same positive effect as the B1R agonist on growth and migration of prostate tumour cells. DU145 CM did not prove to be a migratory stimulus for DU145 cells at any concentration. Discussion Previous studies in our laboratory have shown prostate-tumour CM to promote proliferation of endothelial cells and have postulated that TK up-regulation may be the reason for this. However, the present study could not reproduce this effect of CM. Further, BKR antagonists had no notable or consistent effect on the minimal promotion of proliferation that had been produced by DU145 CM. In addition, selective BKR agonists failed to induce proliferation or migration of endothelial cells, key events in the angiogenic cascade. Although in contrast to some studies, the present study was unable to implicate the KKS in angiogenesis, tumour neo-vascularisation is a consequence of several angiogenic factors functioning together as opposed to a single, isolated factor. For example, we were able to demonstrate a positive mitogenic effect of VEGF on endothelial cells and it may be this as well as other factors in the CM that are responsible for the small proliferation we observed. Up-regulation of kallikreins and kinins in tumours may enhance fundamental events in tumourigenesis in an autocrine manner, and bradykinin (BK) has previously been shown to promote tumour growth in mouse models. Our study supported the involvement of the KKS in tumourigenesis. Although CM from DU145 cells did not self-stimulate the migration of these cells, a B1R agonist enhanced both proliferation and migration, an effect that was also abrogated by the relevant antagonist, indicating a role for kinins. In contrast to the findings of another study, stimulation of the B2R failed to significantly promote tumour growth or motility. However, this is not an unexpected finding because it is thought that the ubiquitous B2R mediates physiological effects in the prostate while the inducible B1R plays a role in prostate cancer pathology. In summary, this study lends support to the ongoing exploration of BKR antagonists as possible candidates in the development of alternate approaches to cancer therapy. This may be particularly beneficial to hormone-independent tumours, such as those of the prostate, for which there exists few effective treatment options.
A cross-sectional survey of patients attitude to vaginal examination and chaperone at King Edward V111 hospital.
(2012) Amaechina, Okezie Ubaka.; Ramnarain, Harry.
Abstract available in PDF file.
Clinical profile of HIV negative and HIV positive women presenting with cervical cancer in Durban.
(2013) Ghani, Ayesha.; Bagratee, Jayanthilall Sarjoo.
Abstract available in PDF file.
Abnormal IgA1 O-glycosylation in a multi-ethnic population of IgA nephropathy patients in KwaZulu-Natal, South Africa.
(2013) Nansook, Prishani.; Assounga, Alain Guy Honore.
Background: The pathogenesis of IgA Nephropathy (IgAN) is poorly understood globally and curative therapy currently does not exist. Variable presentation among IgAN patients globally may be indicative of various underlying pathogenic mechanisms. Pathogenetic data on IgAN in Africa is scarce to nil. The current study provides the first O-glycosylation data for IgAN in South Africa or Africa. Methods: An enzyme-linked immunosorbent assay-type lectin binding assay was used to compare the serum IgA1 O-galactosylation in 19 IgAN patients and 20 controls. During 2007, 2009, and 2011, blood was extracted from consenting biopsy-diagnosed South African IgAN patients of African, Caucasian, Indian (predominantly) and mixed-race descent in KwaZulu Natal. The mean absorbance value corresponding to the degree of degalactosylation for the IgAN group was compared to that of the normal control group for each test. A non-parametric Wilcoxon matched-pairs test was used accordingly. The two-tailed p-value was used to assess for statistical significance between the groups. The low number of attending and consenting IgAN patients precluded IgA1 O-galactosylation analyses between race, gender, and disease stage. Results: The average means of the experiments for the IgAN group is 0.3678 ± 0.0790 (SEM) and is statistically significantly greater than the normal control group which is 0.2969 ± 0.0586 (SEM); (p = 0.0076). Conclusion: Thus, IgAN patients exhibited abnormal IgA1 O-glycosylation with a greater level of terminal degalactosylation of IgA1 in comparison to controls. Such a finding is consistent with other studies in Caucasian and Asian populations globally. Future specific therapeutic strategies that target the formation of abnormal glycosylation in IgA1 may be potentially beneficial in the study population.
A description of the profile of the patients and outcomes of fiber-optic bronchoscopies, performed at a tertiary care hospital in KwaZulu-Natal, South Africa, from January to December 2011.
(2014) Ramkillawan, Yeishna.; Dawood, Halima.
Background Tuberculosis (TB), pneumonia and human immunodeficiency virus (HIV) were the three leading causes of natural deaths in South Africa in 2013 and 11.9% of all deaths in KwaZulu Natal were attributed to TB. In 2013, there was an estimated 5.26 million people infected with HIV in South Africa. HIV infected individuals have an increased risk of respiratory tract infections including smear negative TB. Lung cancer is the most common type of cancer in the world. However, due to infrequent updates of the cancer registry in South Africa, current prevalence is unknown. Bronchoscopy is a useful tool for the diagnosis of broncho-respiratory pathology. Aims and Objectives This study describes the patient profile and outcomes of bronchoscopy in a tertiary centre in KwaZulu Natal in 2011. Specific objectives were to describe bronchoscopy indications, microbiological, cellular and histological findings and prevalence of TB amongst smear negative patients by broncho-alveolar lavage (BAL). In addition, the common types of lung cancer diagnosed on biopsy during bronchoscopy were to be described. Background Tuberculosis (TB), pneumonia and human immunodeficiency virus (HIV) were the three leading causes of natural deaths in South Africa in 2013 and 11.9% of all deaths in KwaZulu Natal were attributed to TB. In 2013, there was an estimated 5.26 million people infected with HIV in South Africa. HIV infected individuals have an increased risk of respiratory tract infections including smear negative TB. Lung cancer is the most common type of cancer in the world. However, due to infrequent updates of the cancer registry in South Africa, current prevalence is unknown. Bronchoscopy is a useful tool for the diagnosis of broncho-respiratory pathology. Aims and Objectives This study describes the patient profile and outcomes of bronchoscopy in a tertiary centre in KwaZulu Natal in 2011. Specific objectives were to describe bronchoscopy indications, microbiological, cellular and histological findings and prevalence of TB amongst smear negative patients by broncho-alveolar lavage (BAL). In addition, the common types of lung cancer diagnosed on biopsy during bronchoscopy were to be described. Background Tuberculosis (TB), pneumonia and human immunodeficiency virus (HIV) were the three leading causes of natural deaths in South Africa in 2013 and 11.9% of all deaths in KwaZulu Natal were attributed to TB. In 2013, there was an estimated 5.26 million people infected with HIV in South Africa. HIV infected individuals have an increased risk of respiratory tract infections including smear negative TB. Lung cancer is the most common type of cancer in the world. However, due to infrequent updates of the cancer registry in South Africa, current prevalence is unknown. Bronchoscopy is a useful tool for the diagnosis of broncho-respiratory pathology. Aims and Objectives This study describes the patient profile and outcomes of bronchoscopy in a tertiary centre in KwaZulu Natal in 2011. Specific objectives were to describe bronchoscopy indications, microbiological, cellular and histological findings and prevalence of TB amongst smear negative patients by broncho-alveolar lavage (BAL). In addition, the common types of lung cancer diagnosed on biopsy during bronchoscopy were to be described. Methods A retrospective review of consecutive bronchoscopies performed by the pulmonologist at a tertiary hospital in western KwaZulu Natal, between 1 January and 31 December 2011 was performed. A total of 107 patients met the inclusion criteria. Data was collected from clinical records, laboratory and radiology computerised record systems and entered on an Excel workbook using Microsoft Office 2010® software. Data was analysed using Epi-Info Version 3.5.4® and Stata/IC 13.0®. The demographic, bronchoscopy and chest CT scan findings were summarised with descriptive summary measures and expressed as means ± standard deviation (SD) and/or medians with the range and interquartile range for quantitative variables. Percentages, frequencies and proportions were used to describe categorical variables. Results The median age of patients was 55 ± 14.4 (Interquartile range (IQR) 43 - 63) years and 68 (63.6%) patients were male. Twenty-eight (26.2%) patients were HIV infected with a median cluster of differentiation 4 count of 254 ±164 (IQR 126 – 366.5) cells per cubic millimetre. Nine patients were on antiretroviral therapy. The commonest indications for bronchoscopy were investigation of a lung mass (35.8%), non-resolving lower respiratory tract infection (15%) and suspected TB (15%). Microbiological findings on BAL samples included gram positive and negative bacteria (14%) and fungi (20%). TB microscopy, polymerase chain reaction and culture revealed mycobacterium tuberculosis on 22.2% of all BAL samples. Two patients with mycobacterium tuberculosis on BAL samples were HIV infected. The prevalence of TB on smear negative patients was 11.1%. Cytological analysis of BAL samples detected pathology on eight (13.1%) patients and two (3.3%) of these patients had lung cancer. Malignant (52.9%) (squamous cell carcinoma and adenocarcinoma) and benign (11.1%) (pneumonia and interstitial fibrosis) pathology was found on histology. Squamous cell carcinoma (37%) was the commonest lung cancer detected. Bronchoscopy was helpful in determining broncho-respiratory pathology in 38 (35.5%) patients. The commonest diagnosis was lower respiratory tract infection in 7 of 15 (46.7%) patients referred with diffuse pulmonary infiltrates. Bronchoscopy also assisted with the diagnosis of lung cancer in 20 of 43 (46.5%) patients referred with suspected lung mass. Overall the procedure complication rate was 3.7%. Conclusion Bronchoscopy may be a useful tool in diagnosing and decreasing the morbidity associated with respiratory illness in South Africa as the diagnostic yield was greatest for lower respiratory tract infections. Samples collected during BAL had a relatively low diagnostic yield for TB. Prompt referral of smear negative TB suspects is recommended to assist with the microbiological diagnosis of TB and direct therapy thereof. Cytological examination of BAL samples was associated with a low yield of lung cancer and biopsy samples were more useful for this purpose. SCC was the commonest histological subtype of lung cancer in this cohort. Bronchoscopy was a relatively safe procedure in determining the aetiology of broncho-respiratory pathology.
An assessment of DSP pharmacy medication delivery for HIV treatment in a family practice in KwaZulu-Natal.
(2014) Reddy, Vinothan Vadival.; Mahomed, Ozayr Haroon.
Abstract available in PDF file.
Size does not matter: a molecular insight into the biological activity of chemical fragments utilizing computational approaches.
(2016) Munsamy, Geraldene.; Soliman, Mahmoud Elsayed Soliman.
Insight into the functional and physiological state of a drug target is of essential importance in the drug discovery process, with the lack of emerging (3D) drug targets we propose the integration of homology modeling which may aid in the accurate yet efficient construction of 3D protein structures. In this study we present the applications of homology modeling in drug discovery, a conclusive route map and detailed technical guideline that can be utilised to obtain the most accurate model. Even with the presence of available drug targets and substantial advancements being made in the field of drug discovery, the prevalence of incurable diseases still remains at an all-time high. In this study we explore the biological activity of chemically derived fragments from natural products utilising a range of computational approaches and implement its use in a new route towards innovative drug discovery. A potential avenue referred to as the reduce to maximum concept recently proposed by organic chemists, entails reducing the size of a chemical compound to obtain a structural analogs with retained or enhanced biological activity, better synthetic approachability and reduced toxicity. Displaying that size may not in fact matter. Molecular dynamic simulations along with toxicity profiling were comparatively performed, on natural compound Anguinomycin D and its derived analog SB 640 each in complex with the CRM1 protein which plays an avid role in cancer pathogenesis. Each system was post-dynamically studied to comprehend structural dynamics adopted by the parent compound to that exhibited by the analog. Although being reduced by 60% the analog SB 640 displayed an overall exhibition of attractive pharmacophore properties which include minimal reduction in binding affinity, enhanced synthetic approachability and reduced toxicity in comparison to the parent compound. Potent inhibitor of CRM1, Leptomycin B (LMB) displayed substantial inhibition of the CRM1 export protein by binding to four of the PKIαNES residues (ϕ0, ϕ1, ϕ2, ϕ3, and ϕ4) present within the hydrophobic binding groove of CRM1. Although being drastically reduced in size and lacking the presence of the polyketide chain present in the parent compound Anguinomycin D and LMB the analog SB 640 displaced three of these essential NES residues. The potential therapeutic activity of the structural analog remains undeniable, however the application of this approach in drug design still remains ambiguous as to which chemical fragments must be retained or truncated to ensure retention or enhanced pharmacophore properties. In this study we aimed to the use of thermodynamic calculations, which was accomplished by incorporating a MM/GBSA per-residue energy contribution footprint from molecular dynamics simulation. The proposed approach was generated for each system. Anguinomycin D and analog SB 640 each in complex with CRM1 protein, each system formed interactions with the conserved active site residues Leu 536, Thr 575, Val 576 and Lys 579. These residues were highlighted as the most energetically favourable amino acid residues contributing substantially to the total binding free energy. Thus implying a conserved selectivity and binding mode adopted by both compounds despite the omission of the prominent polyketide chain in the analog SB 640, present in the parent compound. A strategic computational approach presented in this study could serve as a beneficial tool to enhance novel drug discovery. This entire work provides an invaluable contribution to the understanding of the phenomena underlying the reduction in the size of a chemical compound to obtain the most beneficial pharmacokinetic properties and could largely contribute to the design of potent analog inhibitors for a range of drug targets implicated in the orchestration of diseases.
A retrospective review of the demographic profile, disease activity, co-existent co-morbid disease and treatment in established rheumatoid arthritis at a tertiary center clinic.
(2016) Singh, Akira.; Paruk, Farhanah.; Magula, Nombulelo Princess.
Rheumatoid arthritis (RA) is one of the most common forms of chronic inflammatory arthritis and often results in joint damage, physical disability and premature mortality. The incidence of RA is increasing in developing countries, especially in urban areas amongst lower socio-economic groups. There is a dearth of data on non-communicable diseases such as RA in South Africa (SA) as resources and research is concentrated on addressing the high burden of communicable diseases due to human immunodeficiency virus (HIV) and tuberculosis (TB) compounded with addressing high maternal and infant mortality rates. Therefore despite the severity and resultant functional disability, RA remains poorly understood and often mismanaged. This study aims were to understand the natural history of patients with RA treated in a public sector tertiary clinic. The objectives of this retrospective study are to describe the demographic profile, disease activity, drug management and comorbid disease profile in patients with established RA attending a dedicated rheumatic clinic at King Edward VIII Hospital in Durban. A retrospective chart review was conducted of the files of all RA patients attending the arthritis clinic at King Edward VIII Hospital, for a period of at least ten years. The demographic data, serological status, current disease activity, functional class, co-morbid diseases, and treatment were recorded on a structured data collection tool. In this study, Indians comprised the majority (n=81, 58.7%) followed by Blacks (n = 51, 36.9%). All the patients met the clinical criteria for RA on the initial visit, with 73 (63.5%) having a positive rheumatoid factor (RF). Synovitis was still observed in 35.5% of patients at their last visit and in these patients the C-reactive protein remained elevated at ≥ 16 mg/dL (p < 0.0001). Radiographs showed a significant deterioration in terms of erosions between the two time points (p < 0.021). Hypertension was the most frequent co-morbid disease seen in 96 (69.6%) patients. There were several limitations as this was a retrospective study and therefore there were a number of files that had incomplete or missing data. The clinical assessment of disease was performed by several clinicians and inter-observer variability was another shortcoming. Further the study was limited to the public sector only and potentially excluded other ethnicities and therefore may also not be an accurate reflection of natural history of RA in SA. This study highlights the need for better and tighter RA control in the SA public sector and the need for prospective studies with adequate representation of all ethnic groups to evaluate the challenges faced in delivering an effective rheumatology service in SA.

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