Includes bibliographical references (leaves 140-161). / Human saliva, breast milk and cervical secretions contain several non-immunological components including mucins (mucous glycoproteins), which protect the gastrointesinal and female reproductive tracts and breast fed infants from bacterial, viral and fungal infections. In addition to their well known function in lubrication, tissue coating and digestion, mucus and mcins have been used as pathological markers in diseases such as asthma, chronic bronchitis, cystic fibrosis, and carcinomas of the breast, lung and colon. Crude saliva is a also known to inhibit the activity of human immunodeficiency virus (HIV), the causative agent of acquired immunodeficiency syndrome (AIDS). According to the joint United Nations Programme on HIV/AIDS (UNAIDS) worldwide an estimated 38.6 million people were living with HIV in 2005 with 401 million newly infected and 2.8 million deaths. It has been reported that an estimated 24.5 million of the HIV infected people of whom 60% females live in sub-Saharan Africa with the Southern African region having the highest prevalence in Africa. Furthermore the incidence of opportunistic diseases such as TB is also reported to increase with HIV prevalence. Thus far, despite the discovery of highly active antiretroviral therapies which contain both protease and reverse transcriptase inhibitors, HIV remains as a global threat especially to the third world countries. Therefore there is a need for the development of safe compounds to reduce viral loads in infected people and to prevent the transmission of the virus from one individual to another. The search for a suitable vaccine is ongoing.

Includes abstract. / Includes bibliographical references. / The aim of this study primarily was to review pathological reports of all symptomatic third molar teeth removed in a private practice, and to use the data to support or refute routine removal of third molar teeth. All patients who underwent third molar tooth removal for symptoms,either systemic or local ,in a private practice over a twenty year period between 1987 and 2007 were included in the study. Specimens were sent for histological assessment by Oral Pathologists. The patient records were reviewed retrospectively. A total of 3427 third molar teeth were included in the study. There were 68.75% specimens which had some sort of pathology. Only 0.3% of specimens were reported as normal dental follicular tissue. There were 31.25% specimens of hyperplastic follicular tissue which was considered non pathologic as they consisted of normal dental follicular tissue with a mild chronic inflammatory cell infiltrate. However the 68.75% pathologic lesions consisted of 14.44% specimens with early dentigerous cysts, 8.11% with dentigerous cysts, 42.80% of paradental cysts and the remainder with other pathologies. The majority of the patients were in the second and third decades and mostly female. The age distribution of the patients suggested a progression from hyperplastic follicular tissue with a peak occurring at 17 years, to early dentigerous cysts at 19 years, to dentigerous cysts at 21 years. Paradental cyst formation, with a peak incidence at 19 years of age formed a large number of the pathological lesions found, and accounted for a large number of patients seeking treatment, owing to the symptoms associated. This study represents an analysis of the largest number of symptomatic third molar teeth submitted for histological assessment known. The data obtained was used to review the guidelines for the management of third molar teeth. From this study it can be concluded that symptomatic impacted third molar teeth should be removed early in the third decade in order to avoid general or local symptoms suffered by these patients.

In order to address crucial existing limitations in the assessment and analysis of pancreatic injuries due to the lack of robust data and deficient surgical strategies, this thesis focused on priority topics to resolve existing unanswered and under-researched questions in the management of complex pancreatic injuries. Each of the twelve clinical studies in this thesis evaluated a specific aspect of pancreatic trauma based on the detailed analysis of prospective granular data from a large cohort of patients treated in an academic surgery and trauma centre with substantial experience in civilian operative trauma care in which standard and uniform protocols were applied.

Introduction Emergency centres have to be equipped to provide high-quality care to a number of undifferentiated patients with varying acuity of illness. This study aimed to identify the most common presenting complaints and corresponding linked diagnoses, in total and for each category of the South African Triage Scale (SATS) at Khayelitsha Emergency Centre (EC). Methods A retrospective, cross-sectional, chart review was used. The sample consisted of patients who presented to Khayelitsha EC in January and June 2015. Charts were reviewed via the Electronic Content Management system. Data were collected on demographic profile, triage priority, presenting symptoms at triage, and ICD-10 diagnosis. Results 4006 of 4928 charts that were reviewed were suitable for inclusion. Triage acuity was 28.0% (n=1123) green, 34.2% (n=1372) yellow, 25.7% (n=1030) orange and 3.5% (n=141) red. The most common presenting complaints were trauma (10.3%) and pain (10.1%); the majority of these patients presented in the yellow and green triage categories. The most common diagnosis made in the EC was pneumonia (7.0%) - most frequently presenting as shortness of breath (8.7%) and cough (5.6%). Medical conditions presented with a higher acuity at triage. Presenting complaints documented at triage and those reported by clinicians correlated an acceptable 70.1% of cases (r=0.71). Diarrhoea and vomiting were the predominant symptoms in summer whereas shortness of breath and cough were more frequent in winter. Triage acuity was similar for both months. Conclusion Individual symptoms presented with varying priority and resulted in a variety of eventual diagnoses which showed differences across categories. Presenting complaints provide granularity to otherwise undifferentiated triage priorities. Future research should focus on time-in-motion work to determine the mean clinical care time each of these complaints require. This should allow a calculation of the mean clinical care time for each triage priority. In turn this can be turned into a calculation for optimal staffing.

Includes bibliographical references (leaves 101-138). / The thin layer of crude mucus lining the human gastric mucosa protects the delicate gastric epithelium from the high shear forces associated with digestion. Gastric mucus is composed largely of water (>90%) and a complex mixture of organic components such as enzymes, various serum and cellular macromolecules, sloughed cells, bactericidal proteins, plasma proteins, inorganic ions and very importantly the mucins, that impart to it its gel-forming properties. Mucins are large heterogenous polymers that are difficult to characterize by traditional biochemical methods. However mucins from different regions of the body do share common features such as a low protein content of approximately 20% by weight and a carbohydrate content of 70 to 80% by weight. Mucins are characterized by a variable number of tandem repeat regions rich in serine, threonine and proline with the serine and threonine being potential sites for O-glycosylation. In contrast to the glycosylated region is the 'naked' region rich in cysteine and susceptible to proteolysis. The cysteine residues enable mucin monomers to form polymers by disulphide bridges. Alterations of mucin expression take place in gastric carcinomas. Our laboratory previously reported the presence of a 40-50 kDa glycoprotein in the mucus of patients with gastric cancer that associated with albumin. The primary aims of our study were to develop an antibody to this 40-50 kDa glycoprotein, and to determine the location of its expression in gastric tissue by the immunohistochemical method, ranging from normal, to premalignant to cancer. The final aim was to identify this unknown glycoprotein by proteomic analysis. The reactivity of the antibody to the mucin and its 40-50 kDa component was determined by Western Blotting.

As surgery assumes a greater position in the global health agenda, the need to not only improve access to surgical care but also improve the quality of surgical care, is paramount. Surgical quality improvement programmes have been shown to reduce morbidity and mortality following surgery. A key first step to the design and implementation of a structured surgical quality improvement programme is the collection and analysis of high-quality data. To quote Dr. Margaret Chan, the director general of the World Health Organisation, '…the real need (in global health) is to close the data gaps, especially in low and middle-income countries, so that we no longer have to rely heavily on statistical modeling for data on disease burden.' In this thesis it was hypothesized that emerging m-Health technology, defined as medical and public health practices supported by the use of mobile devices, would provide a solution to close such data gaps. Various m-Health applications were used to develop three databases describing the outcomes of major surgery performed within the Cape Metro West health district during the study period. After reviewing the design and analytical rationale of the American College of Surgeons National Surgical Quality Improvement Programme and Trauma Quality Improvement Programme, these de novo databases were used to develop three quality improvement programmes designed for local implementation: The Essentials programme for general and vascular surgery, a Procedure-targeted programme and a trauma quality improvement programme. Key to these programmes was the derivation and validation of prediction rules which reliably estimate the probability of an adverse outcome following major surgery in a risk-adjusted manner. Such rules promote internal and external benchmarking over time to identify opportunities for quality improvement and critically appraise the impact of any corrective action implemented. In order to improve the quality of surgical care we provide, a continuous cycle of monitoring, assessment, and management should be performed routinely. This thesis provides some guidance of how this can be done within the Cape Metro West health district.

Introduction: Troponin I tests have been shown to be accurate and are relied upon to assist in making critical decisions regarding patient care in patients presenting with chest pain. The tests are expensive, however, and so their rational use becomes extremely important in a budget-constrained public health sector. The aim of this study was to describe how Troponin I tests are used throughout Victoria Hospital, by a range of requesting clinicians, working in different specialties. Methods A cross-sectional, prospective design was employed, using multiple data sources. We collected a consecutive sample over a three-month period from Victoria hospital’s Emergency Centre using a dedicated data collection tool connected to use of the point-of-care troponin I test. We supplemented this prospective sample with outcome data, using the hospital’s electronic admission record. Results Three hundred and sixteen patient entries were included in the final results. The majority of Troponin tests were negative (70%). Discharge directly from Emergency Centre was 10% in Troponin I positive patients, 37,5% in Equivocal Troponin patients, and 65% in Troponin negative patients. Furthermore, patients were twice as likely to be transferred to a tertiary facility if their Troponin was positive (24%), compared to equivocal (10.4%) or negative (12%). Discussion Chest pain was the most common presenting complaint, with Acute Coronary Syndrome being the most common working diagnosis. The clinical management of patients varied considerably when comparing their Troponin I result. Troponin I appears to be used as an effective rule-out tool in the decision-making pathway.

Background: Upper gastrointestinal bleeding (UGIT) is a common presentation to hospital and can result in a significant morbidity, mortality and hospital costs. Consensus guidelines are present from various international expert bodies regarding the management of these patients and compliance with these guidelines is variable and is dependent on rigorous implementation and continuous audits. Aim: The primary aim of this study is to evaluate complaints to three aspects of management of UGITB (time of endoscopy ,use of dual endotherapy and haemoglubin trigger for transfusion) at Acute Care Surgery Unit, at Groote Schuur Hospital. Methods: This is a comparative study between a retrospective control group and a prospective cohort post implementation of a quality improvement program (QIP). Results: This study included 109 patients, 51 in the control and 58 in the QIP group. The two groups were statistically comparable in terms of demographics, clinical presentation, referral pattern and endoscopy finding. Over 80% in both groups had their endoscopy within 24 hours (Control 83.7%, QIP 81.6%). Time to endoscopy was not statistically significantly different between the Control and QIP groups for low and high-risk patients ((suspected varices or Modified Glasgow-Blatchford Score (MBS) >10)). However, when both groups are combined, patients with an MBS of >10 or more had a statistically shorter 'Time to scope’ by 8 hours than those with a score < 10 (p=0.02).

Heat-related mortality in US cities is expected to more than double by the mid-to-late 21st century. Rising heat exposure in cities is projected to result from: 1) climate forcings from changing global atmospheric composition; and 2) local land surface characteristics responsible for the urban heat island effect. The extent to which heat management strategies designed to lessen the urban heat island effect could offset future heat-related mortality remains unexplored in the literature. Using coupled global and regional climate models with a human health effects model, we estimate changes in the number of heat-related deaths in 2050 resulting from modifications to vegetative cover and surface albedo across three climatically and demographically diverse US metropolitan areas: Atlanta, Georgia, Philadelphia, Pennsylvania, and Phoenix, Arizona. Employing separate health impact functions for average warm season and heat wave conditions in 2050, we find combinations of vegetation and albedo enhancement to offset projected increases in heat-related mortality by 40 to 99% across the three metropolitan regions. These results demonstrate the potential for extensive land surface changes in cities to provide adaptive benefits to urban populations at risk for rising heat exposure with climate change.

Eicosanoid production by macrophages is an early response to microbial infection that promotes acute inflammation. The intracellular pathogen Listeria monocytogenes stimulates arachidonic acid release and eicosanoid production from resident mouse peritoneal macrophages through activation of group IVA cytosolic phospholipase A2 (cPLA2α). The ability of wild type L. monocytogenes (WTLM) to stimulate arachidonic acid release is partially dependent on the virulence factor listeriolysin O; however, WTLM and L. monocytogenes lacking listeriolysin O (ΔhlyLM) induce similar levels of cyclooxygenase 2. Arachidonic acid release requires activation of MAPKs by WTLM and ΔhlyLM. The attenuated release of arachidonic acid that is observed in TLR2-/- and MyD88-/- macrophages infected with WTLM and ΔhlyLM correlates with diminished MAPK activation. WTLM but not ΔhlyLM increases intracellular calcium, which is implicated in regulation of cPLA2α. Prostaglandin E2, prostaglandin I 2, and leukotriene C4 are produced by cPLA 2α+/+ but not cPLA2α-/- macrophages in response to WTLM and ΔhlyLM. Tumor necrosis factor (TNF)-α production is significantly lower in cPLA2α +/+ than in cPLA2α-/- macrophages infected with WTLM and ΔhlyLM. Treatment of infected cPLA 2α+/+ macrophages with the cyclooxygenase inhibitor indomethacin increases TNFα production to the level produced by cPLA 2α-/- macrophages implicating prostaglandins in TNFα down-regulation. Therefore activation of cPLA2α in macrophages may impact immune responses to L. monocytogenes.