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In this thesis I examined the role of circulating monocytes and lung macrophages in the pathogenesis of the early fibrotic, progressive fibrotic and resolution phases of pulmonary fibrosis. Pulmonary fibrosis with destruction of lung architecture and consequent respiratory failure and death represents a massive worldwide health burden. Although idiopathic pulmonary fibrosis (IPF) is the archetypal and most common cause of lung fibrosis, numerous respiratory diseases can progress to pulmonary fibrosis, and this usually signifies a worse prognosis. Importantly, the incidence and prevalence of IPF continue to rise and it remains one of the few respiratory conditions for which there are no effective therapies. The mechanisms resulting in pulmonary fibrosis are controversial. Early work in the 1980s and 1990s suggested that lung macrophages were important. However, at the turn of the 21st century there was a shift to a belief that pulmonary fibrosis resulted from aberrant wound healing as a consequence of repetitive epithelial injury from an as yet unknown cause. However, with the ever expanding knowledge of the importance of macrophages in other fibrotic conditions such as the kidney and liver, the potential importance of macrophages in pulmonary fibrosis has become more pertinent. Using an in vivo depletional strategy in several murine models of lung fibrosis, in conjunction with human studies, I sought to characterise the role of circulating monocytes and lung macrophages in the pathogenesis of pulmonary fibrosis. I have established that circulating monocytes and lung macrophages are not critical for the development of early lung fibrosis. In contrast, circulating monocytes and lung macrophages are important during the progressive fibrotic phase of lung fibrosis. Furthermore, my data suggest that the pro-fibrotic alternatively activated macrophages may be the sub-class of macrophages that mediate this fibrogenic effect. In addition and in contrast, I have established that lung macrophages are required for the resolution of fibrosis. This finding is in keeping with important work performed in the field of liver fibrosis. There is an ever increasing literature examining the role of matrix metalloproteinases (MMPs) during tissue fibrosis and repair. My work has suggested that during lung fibrosis there may be compartmental specific functions of MMPs that regulate lung fibrogenesis, although more work is required before this exciting finding can be properly defined.

Purpose: To compare the pulmonary function of older runners with non-runners and also the population norms. Method: 40 males ages 45 to 65 were compared for respiratory muscle strength, spirometry and maximum voluntary ventilation. Univariate and multivariate analysis (p < 0.05) were used to determine differences Results: No significant differences in age, height, or respiratory muscle strength were found. A significant difference was found for weight and BMI with the non-runners having greater values. The dependent variables of FVC, FEV1, FEF25-75%, PEF, and MVV resulted in a significant difference with the runners having greater values. A significant difference was also found for pulmonary function between runners and the general population. Conclusion: Continued and habitual aerobic exercise in the form of running in 45 to 65 year old men resulted in pulmonary function values that were significantly greater than those of the non-runners and also greater than population norms.

A research report submitted to the Faculty of Heath Sciences, University of the Witwatersrand, in partial fulfilment of the requirements for the degree of Master of Science in Medicine in the field of Tropical Diseases (Epidemiology & Biostatistics) Johannesburg, / Objective. The aim of this paper was to systematically evaluate available evidence on tobacco smoking as a risk factor for pulmonary tuberculosis. Methods. Relevant reports were identified by a systematic electronic search of Medline, Pubmed, Nioshtic, Toxline and Embasse. Methodological quality of all selected publications was assessed using a standardized checklist. Information was collected on all major study characteristics. Inter-study heterogeneity was examined qualitatively and statistically using the DerSimonian and Laird method. Results. Five case-control studies and 1 cohort study were included in the systematic review. All the 6 studies revealed a relationship between tobacco smoking and pulmonary tuberculosis. Heterogeneity across studies hampered overall statistical pooling of results, however pooled risk ratios for sub-groups were determined / IT2018

"Magnetic resonance imaging (MRI) has emerged as the imaging modality of choice in a wide variety experimental and clinical applications. In this dissertation, I will describe novel MRI techniques for the characterization of neural and pulmonary vascular function in preclinical models of disease. In the first part of this dissertation, experimental results will be presented comparing the identification of ischemic lesions in experimental stroke using dynamic susceptibility contrast (DSC) and a well validated arterial spin labeling (ASL). We show that DSC measurements of an index of cerebral blood flow are sensitive to ischemia, treatment, and stroke subregions. Further, we derived a threshold of cerebral blood flow for ischemia as measured by DSC. Finally, we show that ischemic lesion volumes as defined by DSC are comparable to those defined by ASL. In the second part of this dissertation, a methodology of visualizing clots in experimental animal models of stroke is presented. Clots were rendered visible by MRI through the addition of a gadolinium based contrast agent during formation. Modified clots were used to induce an experimental embolic middle cerebral artery occlusion. Clots in the cerebral vasculature were visualized in vivo using MRI. Further, the efficacy of recombinant tissue plasminogen activator (r-tPA) and the combination of r-tPA and recombinant annexin-2 (rA2) was characterized by clot visualization during lysis. In the third part of this dissertation, we present results of the application of hyperpolarized helium (HP-He) in the characterization of new model of experimental pulmonary ischemia. The longitudinal relaxation time of HP-He is sensitive to the presence of paramagnetic oxygen. During ischemia, oxygen exchange from the airspaces of the lungs to the capillaries is hindered resulting in increased alveolar oxygen content which resulted in the shortening of the HP-He longitudinal relaxation time. Results of measurements of the HP-He relaxation time in both normal and ischemic animals are presented. In the final part of this dissertation, I will present results of a new method to measure pulmonary blood volume (PBV) using proton based MRI. A T1 weighted, inversion recovery spin echo sequence with cardiac and respiratory gating was developed to measure the changes in signal intensity of lung parenchyma before and after the injection of a long acting intravascular contrast agent. PBV is related to the signal change in the lung parenchyma and blood before and after contrast agent. We validate our method using a model of hypoxic pulmonary vasoconstriction in rats."

A dissertation submitted to the Faculty of Medicine, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the Degree of Master of Medicine. J o h a n n e s b u r g 1988 / Infections can cause autoantibody production. The purpose of this study was to determine the prevalence of autoantibodies in chronic mycobacterial infections in Johannesburg. Sera from 41 leprosy patients and from 49 untreated and 73 treated tuberculosis patients were tested for rheumatoid factor, antibodies against a panel of nuclear antigens, anticardiolipin antibodies and syphilis serology. The antinuclear antibody was positive in 7.3% of the leprosy group, 6.1% of the untreated TB group and 15% of the treated tuberculosis patients (p=0.0125). Antinuclear antibody positivity correlated with duration of treatment (p=0.025). The antinuclear antibody titres were low and there was no specific pattern. / IT2018

Thesis (Ph. D.)--University of Hong Kong, 2001. / Includes bibliographical references.

Thesis--Ph. D., University of Hong Kong, 1980.