Includes abstract. / Includes bibliographical references. / Cardiovascular diseases account for one third of all deaths worldwide, more than 33% of which are related to ischaemic heart disease, involving a myocardial infarction (MI). Emerging MI therapies involving biomaterial injections have shown some benefits; the underlying mechanisms of which remain unclear. Computational models offer considerable potential to study the biomechanics of a myocardial infarction and novel therapies. Geometrical data of a healthy human left ventricle (LV) obtained from magnetic resonance images (MRI) was used to create a finite element (FE) mesh of the LV at the end-systolic time point using Continuity® 6.3 (University of California in San Diego, US). A mesh of 96 hexahedral elements with high order basis functions was employed to adequately describe the geometry of the LV. Simulations of diastolic filling and systolic contraction were performed using a transversely isotropic exponential strain energy function and a model for active stress based on contraction at the cellular level. An anterior apical, transmural MI was modelled in the LV encompassing 16% of the LV wall volume. The infarct was modelled at acute and fibrotic stages of post-infarct LV remodelling by altering the constitutive and active stress models to best describe passive and active behaviour of the ischaemic myocardium at each time point. The geometry of the LV with the fibrotic infarct was adjusted to represent the wall thinning that occurs during LV post-MI remodelling. Hydrogel injection was modelled as layers with material properties differing from those of the surrounding myocardium while accounting for thickening of the LV wall at the injection site. The study design comprised a healthy case and two infarcted cases with and without hydrogel injection. The end-diastolic volume (EDV) increased in the acute infarct model compared to the healthy case due to the reduced stiffness in the infarct wall. An EDV increase was not observed in the fibrotic infarct model compared to the healthy case. This was partially attributed to the increase in infarct stiffness and partially due to the fact that remodelling-related dilation of the LV was not implemented in the model. Inclusion of hydrogel lowered EDV in both the acute and fibrotic models. The predicted ejection fraction (EF) decreased from 41.2% for the healthy case to 28.5% and 33.0% for the acute and fibrotic infarct models, respectively. Inclusion of hydrogel layers caused an improvement in EF in the acute model only.

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Includes bibliography. / The aim of this study was to develop a practical and reproducible multi-marker RT-PCR essay, with the emphasis on achieving maximum specificity for the detection of melanoma nodal metastases. A novel protocol for the efficient homogenisation of nodal tissue was developed, with clinical applicability as the objective.

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Includes bibliographical references (leaves 93-107). / Introduction: Distal sensory polyneuropathy (DSP), the most common neurological complication of HIV infection, is related to either HIV or antiretroviral therapy (ART). Dideoxynucleoside reverse transcriptase inhibitors such as stavudine are widely used in resource-poor countries and often associated with neuropathy. The prevalence of DSP in developed countries range from 21% to 63%; little data is available from Africa. We aimed to estimate the prevalence of DSP in a South African community clinic-based population and to investigate associated risk factors. Methods: In a cross-sectional study, DSP status was determined in 598 HIV-infected adults using validated tools (Brief Peripheral Neuropathy Screen and a modified version of the Total Neuropathy Score) to categorize subjects. Symptomatic DSP required the presence of at least two neuropathic signs together with at least one symptom. Asymptomatic DSP required the presence of two neuropathic signs. Clinical, anthropometric, quality of life and laboratory evaluations were prospectively performed. Information about CD4 counts, antiretroviral therapy (ART) and questionnaires regarding previous tuberculosis (TB) and alcohol exposure was retrospectively collected Results: Approximately half (49%) of the study population were diagnosed with DSP (30% symptomatic DSP). In the ART-naïve group 37% had evidence of neuropathy (23% symptomatic) compared to 63% of the ART-exposed subjects (39% symptomatic). Overall, subjects with DSP were older (p<0.001) and had lower CD4 counts (p<0.001) compared to those without neuropathy. Previously treated TB infection (p<0.001) and ART use (p<0.001) showed strong associations with DSP. In multivariate analyses the odds (95% confidence interval) of developing DSP was independently associated with ART use (OR 1.7, 1.0-2.9), age (per 10 year increments) (OR 1.7, 1.4-2.2) and previously treated TB infection (OR 2.0, 1.3-3.0). Although stavudine significantly associated with DSP, the duration of exposure was similar irrespective of neuropathy status. Pain or paresthesia was reported by 69% of those with symptomatic DSP and rated as at least moderate to severe. ART-exposed subjects had a tendency towards lower pain scores compared to ART-naïves (p=0.032). Conclusions: DSP is a clinically significant problem in urban HIV-infected Africans. The findings of this study raise the possibility that with avoidance of stavudine-containing regimens in older subjects, especially those with a history of previously treated TB infection, the prevalence of DSP may be reduced.

The desired healing response to electrospun scaffolds in tissue engineering is often limited by poor ingrowth due to insufficient porosity, thrombogenicity, lack of vascularisation and/or excessive inflammation. This study aimed at increasing structural porosity and incorporating/delivering anti-thrombotic/angiogenic (heparin) and anti-inflammatory (dexamethasone) agents. Porosity enhancement techniques were explored using two different approaches i) electrospinning of biostable polymer (Pellethane® , Pel) with concomitant electrospraying of soluble microparticles, which were subsequently removed to increase scaffold interconnectivity and ii) electrospinning of biodegradable polymer (DegraPol® , DP) at low collecting temperatures. Dexamethasone (Dex) was incorporated by simple admixture, while heparin (Hep) required chemical modification (heparin tributylammonium, HepTBA) to achieve solubility. Release rates were determined in vitro, followed by thrombogenicity (thromboelastography) and cytotoxicity (cell viability) assessments of modified/unmodified heparin prior to incorporation and after elution. Finally, in vivo responses were evaluated in a subcutaneous model (24 rats) for up to 12 weeks. Porosity was enhanced (P0.1). At 12 weeks of implantation, high-porosity Pel scaffolds allowed for full tissue ingrowth (>98%) while conventional scaffolds were limited (0.3). High-porosity scaffolds produced by combined electrospinning/spraying have the potential to enhance healing. Dex or HepTBA can be incorporated and eluted from degradable electrospun scaffolds, and localised delivery of HepTBA improves implant vascularisation. This study may contribute towards tissue engineered vascular graft development where anti-thrombogenicity and increased vascularisation are desired.

Introduction Pain is the symptom that most frequently brings patients to the hospital and impacts on the quality of patients and their families’ lives, yet researchers have shown that barriers to effective pain management for patients who suffer chronic pain remain. The barriers include professional, patient and system issues. Many of these issues could be seen at the Knysna Provincial Hospital. The literature reveals that the implementation of a guideline increases the success of the pain management process. This research looks at the implementation of a site specific guideline at the Knysna Provincial Hospital. Methodology This study incorporates both quantitative and qualitative analysis. The study has two phases; the first includes a quantitative analysis of file audits and the thematic analysis of three focus groups held to determine barriers and facilitators of the pain management process. Using the information garnered in phase-1 a guideline is developed and implemented. Phase-2 involves the quantitative analysis of files after the implementation of the guideline. Data management and analysis Data from the file audits in both phase-1 and phase-2 was analyzed using quantitative analysis techniques using the software; IBM SPSS 24.0. Data from the focus group discussion was thematically analyzed. Using data from the phase-1 audit and the themes from the focus group discussions a chronic pain management guideline was developed. The guideline was implemented and the phase-2 file audit was performed to establish the effect of the guideline on the pain management process at the Knysna Provincial Hospital. Ethical Considerations All participants of the focus group discussions were given sufficient information about the study to make an informed consent. Ethical approval was obtained from the UCT Faculty of Health Sciences Human Research Ethics Committee. Permission to conduct the research was obtained from the Western Cape Department of Health, Knysna Provincial Hospital, and the Knysna Sedgefield Hospice Board of Directors. Findings This study aimed to identify the barriers and facilitators to good pain management and use the findings to create a guideline. The focus group discussions showed that the current practice was inconsistent; the focus groups identified several barriers and facilitators to improved pain management. The initial file audit showed 84% of patient’s pain was assessed and only 59% were reassessed. Using the data from the file audit and FGD, a guideline was created to meet the needs of the Knysna Provincial Hospital. The file audit post the implementation of the guideline showed improved pain management processes with initial assessment at 100% and reassessment at 71%. The implementation of the new guideline was flawed and only 35% of files audited showed evidence that the new process was used. Conclusion The guideline developed based on the file audits and identification of barriers and facilitators during focus group discussions improved the pain management process at the Knysna Provincial Hospital.

Includes abstract. / Includes bibliographical references (leaves 99-103). / This report presents a computerised tool to analyse the appearance of the lung fields in paediatric chest X-rays to detect the presence of tuberculosis. The computer aided diagnosis (CAD) tool consists of 4 phases: 1) lung field segmentation; 2) lung field subdivision; 3) feature extraction and 4) classification. Lung field segmentation is performed using a semi-automatic implementation of the active shape model algorithm. Two approaches to subdividing the lung fields into regions of interest are compared. The first divides each lung field into 21 overlapping regions of varying sizes, resulting in a total of 42 regions per image; this approach is called the big region approach. The second approach divides the lung fields into a large number of overlapping circular regions of interest. The circular regions have a radius of 32 pixels and are placed on an 8 x 8 pixel grid. This approach is called the circular region approach. Textural features are extracted from each of the regions using the moments of responses to a multiscale bank of Gaussian filters. Additional positional features are added to the circular regions.