Generation of large volumes to cover an existing soft tissue defect is often complicated by the lack of available tissue. The current options for soft tissue reconstruction include local and free flaps, collagen fillers, traditional fat grafting and other synthetic soft tissue fillers. But they all have limitations. Recently, a lot of interest has been generated regarding the use of human adipose derived stem cells for engineering a biocompatible soft tissue construct. Give their ready availability, viability and plasticity they appear to be the ideal building blocks for a cell based soft tissue construct. We find that these cells are easy to isolate in large numbers, easy to maintain in culture and capable of multi-lineage differentiation. hASC's are readily adherent to collagen based scaffolds and these function as the ideal cell delivery matrix. Since most wound beds are ischemic and hypoxic, changes in gene expression of hASC's was studied in conditions of hypoxia and serum deprivation. Microarray PCR results demonstrate the up regulation of 23 angiogenic genes including VEGFC, ANPEP, CXCL6, ANGPLT4 and CXCL5 in conditions of hypoxia. However, this angiogenic response was blunted with the presence of serum starvation in addition to hypoxia. Hence we chose to investigate methods to increase the primary neovascularization of a tissue engineered construct. Our hypothesis was that Europium Nano rods (belonging to the lanthanide series of heavy metals) would increase the angiogenic potential of hASC's. Results of a chick embryo chorioallantoic membrane assay demonstrate that Europium Nano rods potentiate the angiogenic effects of Vascular Endothelial Growth Factor (VEGF) when incorporated in hASC's. These rods are readily incorporated in hASC's by endocytosis and do not affect viability. Hence, we conclude that Europium Nano rods can function as a reliable, nontoxic extrinsic angiogenic stimulus. Further studies are needed to evaluate the 1) effects of ENR's on stem cell plasticity 2) effects on gene expression and 3) further investigate the fate of ENR's with repeated cell division.

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In this study, we explore the effects of NURF depletion on the growth of tumors in immune-competent mice. NURF depletion in tumors results in reduced tumor growth in immune-competent mice, suggesting enhanced anti-tumor immunity. Analysis of the tumor microenvironment by flow cytometry revealed a significantly elevated CD8 and progressively elevated activated CD8 phenotype in Bptf KD tumors, possibly contributing to the increase in cell death and decrease in tumor weight observed. Examination of antigen presentation was evaluated using the OT-1 and Pmel-17 models, though no significant difference in cytotoxicity was observed as measured by LDH and/or IFNγ assays. This indicates possible novel antigen presentation mechanisms in tumor cells, and not increased presentation of existing antigens, contributes to the decreased tumor weight observed in Bptf KD tumors.

The dosing of combination therapies is commonly undertaken empirically by practicing physicians, and there is a lack of a coherent algorithm to approach the problem of combination dosing. Current methods of evaluating multiple drug combinations in clinical trials generally do not provide information regarding the location of more effective dosages when the combination is not found to differ from the standard, even though the absence of a difference does not necessarily mean the new combination is ineffective. Additionally, if a new combination is found to be more effective, often a large proportion of the subjects has not benefited from the trial. This may lead to problems with patient enrollment and adherence to the study protocol, and even with early stopping rules, the time patients spend on inferior treatments may have lasting detrimental effects. This paper describes an evolutionary operation (EVOP) direct-search procedure to titrate combination doses within individual patients. The Nelder-Mead simplex direct-search method is used to titrate a combination of drugs within individual subjects. Desirability functions are incorporated to define the main response of interest and additional responses or constraints. Statistical methodology for determining whether the titrated treatment combination has resulted in an improvement in patient response and for evaluating whether a therapeutic synergism exists is developed. Inferences can be made about the efficacy of the combination or about the individual drugs that comprise the combination. This approach allows every patient the potential to benefit from the combination under study and permits the consideration of multiple endpoints simultaneously.

Nosocomial (hospital-acquired) pneumonia (HAP) continues to be an important cause of morbidity and mortality in the hospital. HAP is the third most common nosocomial infection after urinary tract and surgical wound infections. In addition, HAP is the nosocomial infection with the highest mortality rate. These infections are often difficult to treat, because most are caused by Gram-negative bacilli (GNB) that may be highly resistant to antimicrobial agents. HAPs frequently occur in intensive care patients with underlying lung and/or systemic diseases. Many patients are intubated and are on assisted ventilation. Several sources of infection associated with ventilators or respirators have been described in the past. Most of these sources have been eliminated by improvement in techniques used in the disinfection and cleaning of ventilator equipment. Today, the focus of concern is microbial contamination of the breathing circuit of the ventilator. The Centers for Disease Control (CDC) recommend that the ventilator breathing circuits be changed every 24 hours. The very limited epidemiological and microbiological data from one medical center demonstrate that it may not be necessary to change these circuits as often as every 24 hours. However, before changing this conservative recommendation, more data are needed to establish the safety of changing circuits at longer intervals. The approximate cost of the ventilator circuit is $15. It is estimated that changing ventilator breathing circuits at 48 hours rather than 24 hours would amount to $50,000 per year in savings at the Medical College of Virginia. On a national scale the savings would amount to millions of dollars. Most patients who are placed on ventilatory assistance are supported by continuous volume respirators. Air is humidified when it is passed through a cascade, or wick humidifier. After passage through the humidifier, the gases are delivered to the patient by the inspiratory tubing in the breathing circuit. The inspiratory tubing is connected to the endotracheal tube of the patient by a Yconnector and swivel adaptor. Expired gases from the patient are conducted away by the expiratory tubing which connects to the other limb of the Y-connector. Condensate frequently collects in the respiratory breathing circuit. The warm moist environment of the respiratory circuit is conducive to growth of any microorganisms that may enter the circuit. When the respiratory circuit is contaminated with microorganisms, there is the potential for delivery of bacteria or fungi to the patient's lower respiratory tract. Whether or not infection takes place is determined by one or a combination of several factors including the virulence of the organisms, the size of the inoculum, the presence of foreign bodies in the respiratory tract and the status of host defenses.

Submitted in partial fulfilment of the degree of MSc (Med) in Bioethics and Health Law, Steve Biko Centre for Bioethics, University of the Witwatersrand. Johannesburg, 25 January 2015 / Since his death at the hands of the South African security police on 12 September 1977, much has been written in medical, legal and other literature about Steve Biko. This dissertation explores the medical literature and finds that the vast majority of authors, when writing about Biko, refer primarily to his death, the role of the medical profession in the events leading up to his death, and the ethical issues regarding dual loyalties that arise from studying those issues. In my research question I ask: Does Steve Biko have more to offer medical ethics than his death? In exploring Steve Biko’s writings as collected together in I Write What I Like, I find an underlying thinking which guided Biko’s philosophy. I show that this underlying philosophy is nothing other than the philosophy which underlies ubuntu and I explore how ubuntu should influence our medical ethical thinking and suggest that this could be Biko’s real contribution to medical ethics, namely an ethic that takes seriously the contribution that African moral thinking has to make in the field of medical ethics, a contribution that does nothing less than give to medical ethics a more human face, a contribution which Biko himself believed was what Africa was still to give to the world, a more human face. I critically review the writings and philosophy of Steve Biko and identify key notions or conceptions that are of relevance to medical ethics and then explore the impact and relevance of these key notions and conceptions to the fundamental bioethical issues of autonomy, dignity and confidentiality. I defend the normative claim that integrating Biko’s and other salient African ethical conceptions into our predominantly Western bioethical thinking is a moral requirement.

A thesis submitted to the Faculty of Science, University of the Witwatersrand, Johannesburg, in fulfillment of the requirements for the degree for the Doctor of Philosophy. Johannesburg 2012 / Medical X-ray imaging is nowadays ubiquitous in healthcare. International studies have shown that patient doses during both diagnostic X-ray examinations and fluoroscopically guided procedures from one clinic to another can vary by a factor of up to 100. Such a variation in patient doses offers an opportunity for dose – image quality optimization. Given this background, every radiology clinic which wants to use X-ray imaging ethically and efficiently should have in place ways of optimizing the patient dose – image quality relationship. One generally accepted tool in the optimization process is diagnostic reference levels (DRLs). Currently in South Africa there are no established DRLs and there is no systematic patient dose data collection by the either the national regulator or any competent authority. The main purpose of this thesis was to quantify patient doses for patients undergoing diagnostic examinations and fluoroscopically guided procedures, educate radiation workers on typical patient doses, develop effective methods in quality control of radiographic and fluoroscopic equipment and evaluate radiographer familiarity with digital radiography technology within the context of a typical university teaching South African hospital. The present thesis comprises of seven studies, all carried out at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH), formerly Johannesburg Hospital: Study I: In this investigation the luminance level of X-ray viewing boxes and ambient lighting levels in reporting rooms were measured as a quality assurance procedure and compared with the recommended values by the Directorate of Radiation Control (DRC) of South Africa, European Commission (EC) and Nordic Radiation Protection Co-operation (NORDIC). Results from this investigation showed that the mean average luminance was 1027 cd m-2 and 3284 cd m-2 at the Division of Radiology and Division of Radiation Oncology respectively. The Division of Radiation Oncology had an average viewing box uniformity 7.14% compared to 27.32% at the Division of Radiology. The average ambient lighting was found to be 66 lux for both Divisions. The radiograph viewing conditions variably comply with guidelines. The radiographic imaging chain can only be as strong as its weakest link, thus this study underscores the need of implementing quality control and quality assurance standards in radiographic image viewing. Based on the practical experience of this investigation it is recommended that the DRC test criteria be adopted, in light of the varied recommendations worldwide. Study II: This study aimed to develop, implement and evaluate a software program which can be used in a radiology quality control program. A Microsoft Excel™ based software program was developed for use in quality control: tests data collection, analysis and archiving of the tests done on general radiography equipment, fluoroscopy equipment and film processors. Validation of the software application in terms of usability, user-friendliness was done by an experienced radiographer. This software provides an easier and efficient way of recording quality control data, analysis and archiving. Study III: This study retrospectively analyzed the radiation doses delivered to patients undergoing fluoroscopy guided procedures in terms of the skin dose1 and the kerma-area product readings. A total of three hundred and thirty one fluoroscopically guided procedures were analyzed. In agreement with other published studies, a weak correlation was shown between skin dose and screening time, while a poor correlation was shown between KAP reading and screening time. There was a wide spread in the radiation doses registered for any one given type of examination, which shows that there is room for dose optimization. From the lessons drawn from this study it is practically feasible to record the KAP, fluoroscopy time and number of images routinely. The usefulness and potential use of KAP meters with regards to dose optimization in radiology was confirmed. Study IV: This investigation aimed to assess the feasibility of fabricating in-house the clinical dosimetry radiology phantoms. A total of six patient dose assessment phantoms were fabricated of which four phantoms were as per American National Standards Institute (ANSI) specifications and the other two as per Centre for Devices and Radiological Health (CDRH) specifications. This study proved that the phantoms can be fabricated cost-effectively in-house in a hospital with a mechanical engineering workshop using materials which are locally available. In addition, this study determined radiation doses received by patients undergoing six general radiography examinations. The feasibility of both direct and indirect methods of patient dosimetry was studied. Patient dosimetry based on indirect measurements was the method of choice. Patient data and technical parameters related to the X-ray examinations were collected. The study involved the following examinations: chest posterior-anterior (PA), chest lateral (LAT), pelvis anterior-posterior (AP), abdomen AP, lumbar spine AP and thoracic spine AP. Entrance surface air kerma was calculated based on the X-ray tube 1 See Section 8.3 on the use of the term skin dose output of the unit used and the exposure parameters used for the actual examination. Based on the mean entrance surface air kerma (ESAK) values from the individual rooms, the following DRLs were established: 0.10 mGy for chest PA, 0.22 mGy for chest LAT, 2.98 mGy for pelvis AP, 4.19 mGy for abdomen AP, 5.30 mGy for lumbar spine AP and 3.28 mGy for thoracic spine AP. The calculated mean ESAK values were compared with previously published mean values from other countries. For the first time, a baseline for potential dose reference levels (DRLs) in South Africa was established for the selected examinations. The results of this snapshot audit serve as a benchmark for future dose optimization attempts in South Africa. Feasible and practical dose saving measures are presented and discussed based on the experience of the present patient dose audit carried out. Study V: A replica of the CDRAD phantom was successfully fabricated in-house for use as an image quality test object. It has been shown that the phantom when fabricated in-house is inexpensive and can be made from materials that are readily available locally. Furthermore the utility of the replica phantom as both an acceptance testing and routine quality control tool has been demonstrated. The replica phantom proved effective for purpose and user-friendly. Study VI: The purpose of this study was to assess radiographer familiarity and preferences with digital radiography and thereafter make recommendations in line with the migration from screen film to digital radiography in South Africa. A questionnaire was designed to collect data from either qualified or student radiographers from four teaching hospitals. From the four teaching hospitals there were a total of 205 potential respondents. Among other things, responses regarding experiences and preferences with digital radiography, quality control procedures, patient dose, advantages and disadvantages of digital radiography were sought. The information collected was based on self-reporting by the participants. Sixty-three out of 205 (31 %) radiographers from all the four radiology centres responded to the circulated questionnaire. The participants of this survey showed familiarity with digital radiography and have embraced this relatively new technology as shown by the fact that they can identify both its advantages and disadvantages as applied to clinical practice. However, there are minimal quality control procedures specific to digital radiography being undertaken and there is need for formal education, continuing education and manufacturer training with respect to quality control as institutions make the transition from conventional screen film radiology to digital radiology. Study VII: An investigation into the amount of scattered radiation from the couch during under-couch procedures was carried out. Of dosimetric concern are the forward scattered photons from the couch which contribute in principle to patient dose. Measurement of the amount of scattered radiation off the patient couch was accomplished by using an ionization chamber. The results of the investigation showed that for field size of dimensions, 10 cm * 10 cm, the scatter contribution is approximately 12 % of the total radiation reaching the patient surface. In addition the scatter contribution varies by ±2% across field sizes ranging from 8 cm * 8 cm to 20 cm * 20 cm, with the 10 cm * 10 cm field size taken as a reference field. This study underscores the need to account for the forward scattered radiation so as to improve the accuracy of clinical patient dosimetry. Programs of continuing education and training of radiological personnel in appropriate radiological technique need be actively implemented in order to maintain a high level of awareness of the factors that determine the diagnostic quality and dose to the patients. In line with efforts to optimize dose from diagnostic radiography examinations it is recommended that national DRLs be established in South Africa for the most frequent examinations in general radiography and fluoroscopy. It is recommended that the South African national regulator endeavour to implement or facilitate implementation of a national patient dose database. In summary, this thesis indicates the possibility of dose reduction in diagnostic radiology through optimization of radiographic process.

This research report tells the story of a doctor and a journalist who, at the height of Apartheid’s State of Emergency, placed themselves at risk for the sake of practicing their professions ethically. They chose to defy the law, and bring to the attention of the public, the plight of many detainees who suffered at the hands of the State. In the report, I set out to give an account of the events and to ethically reflect on the actions of the two professionals involved. In particular, I consider the role played by professional codes of conduct in the actions of the two professionals and I reflect on the notion of trust as a centrally important ethical conception with respect to the events described.

MMed (Community Health), Faculty of Health Sciences, University of the Witwatersrand, 2009 / Introduction: This study sought to determine perceptions of registrars of their training on the Wits circuit as regards hospital, specialist and university support and their opinions on improving registrar MMed research output. Future career plans of registrars were also investigated. Methods: This was a cross-sectional study using self-administered questionnaires consisting of Likert scales and open-ended questions. The study population comprised registrars in four clinical specialties on the Wits training circuit. Results: Chris Hani Baragwanath Hospital received the lowest proportion of satisfactory responses for nursing support. Hospital management was considered unsatisfactory at three of the four hospitals. Specialist supervision was considered satisfactory although 70% (115/164) of registrars reported coping with situations beyond their expertise, which they attributed to specialists being off-site. Registrars reported insufficient time and a lack of qualified supervisors as barriers to undertaking research. Only 32% of respondents felt adequately prepared for independent practice. Most registrars intended to continue working in the public sector. Conclusions: Problems and recommendations identified by registrars could be used by the university to improve the registrar training experience.