Thesis (Ph. D.)--University of Wisconsin--Madison, 1981. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 103-126).

Thesis (Ph. D.)--University of Texas at Austin, 2006. / Vita. Includes bibliographical references.

South Africa is one of the high burden countries for TB in Sub Sahara in Africa with Mpumalanga as one of the provinces with a high burden of disease. Data available on tuberculosis in Msukaligwa indicate the following: Cure Rate 40%; Smear conversion at the end of intensive phase 35% and Defaulter Rate 27.5%. The problem of TB is made worse by the twin epidemic of HIV, with a prevalence of 38.9% in our district -the highest among the 3 districts in the province. Retreatment TB carries the risk of developing TB drug resistance with severe consequences for the patient and the population. Understanding the characteristics of these patients will help in designing interventions to prevent the problem, promote a high cure rate for patients with TB in our health care system and reduce to minimum the burden of re-treatment pulmonary TB on our health care facilities and community. One critical precondition for Retreatment TB is non adherence to TB treatment. Factors responsible for non adherence could be classified as individual patient factors; Co-morbid conditions; Health system; treatment related and Community factors. The outcomes of Retreatment TB could be, cure, and death and failure of treatment leading to drug resistance. The Setting of this study is the 58-bedded TB hospital in Ermelo. The Aim of the study was to describe the occurrence, characteristics and management outcome of Retreatment Pulmonary Tuberculosis in patients in the Ermelo TB hospital. The specific Objectives were to describe the socio-demographic, behavioural and clinical factors related to recurrence of the TB in patients; to determine the contribution of non adherence to treatment on recurrence of TB in the study population; to identify the prevalence of resistance to TB medication among patients with Retreatment TB ; to identify treatment outcomes in patients who have been followed up for the duration of Retreatment TB and finally to make recommendations to the Department of Health, Mpumalanga towards minimizing Retreatment TB and improving the overall TB programme. The Study design is cross sectional and descriptive; the study population comprised of patients admitted with TB at Ermelo TB hospital aged 15 years and older between 1 January 2005 and 31 December 2007.No specific probability sampling was applied in the selection of the patients. Data Collection involved visits to the TB hospital during the period and extracting the relevant information from the patient medical records and the TB register using a predesigned data collection form. Data analysis was done by the statistician from the Centre for Statistical Consultation, University of Stellenbosch. Being a descriptive study, the data analysis expresses the prevalence of various factors associated with retreatment TB. This study met the Ethical approval of the University of Stellenbosch as well as the Research Ethics Committee of the Department of Health & Social Services, Mpumalanga. Findings All the three hundred and eighty eight patient records with retreatment TB forming 19.6% of TB patients admitted between 2005 and 2007 were reviewed. The distributions of the patients were: males 66%; mean age of 41.4 years; females 34%; mean age 35.3 years. They were mostly unemployed; primary education 93%; unmarried 43% and married 34%.Retreatment TB was diagnosed with sputum smear microscopy in 71% with bacilli load of 3+ in 45%.The sources of referral to TB hospital were: public hospital 71 %; private doctors 2%. 74% of the patients have had TB 1-3 years before the episode under study. Retreatment TB categories were: after treatment completed 69%; default 19%; after cure 8% and treatment failure 4%. 98% of patients tested had +ve HIV status; the median CD4 cell count was 106 cells/µl at the time of retreatment; very few (5%) were on ART. Drug resistance to primary TB drugs was as follows: Rifampicin 16%; Isoniazid 29%; Ethambutol 19% and Streptomycin 23%. The treatment outcomes for those whom data were available were: successful 49.1%, death 23.8%; treatment default 22.9%. MDR-TB complicated 3.3% of the patients. Conclusion: Majority of the retreatment TB patients were males with an average age of 41years and unemployed. More than two thirds of the patient had completed TB treatment previously and default on treatment accounted for less than one quarter of retreatment categories. The process of care was better in terms of diagnosis of TB with sputum smear. Improvement in the documentation of key factors like smoking, alcohol, drug use among patients and co-morbidity as well as counselling and testing for HIV and provision of ARTs is required. Treatment outcomes with regards to successful outcome need to be monitored and improved upon.

This thesis reviews the current literature on idiopathic pulmonary fibrosis (IPF), a progressive, scarring lung condition largely affecting older adults that is experiencing an increasing incidence in the U.S. and abroad. Two troubling clinical aspects of IPF are the difficulty of timely diagnosis and uncertain progression once diagnosed. The need for early detection is driven by the condition’s median survival rate post-diagnosis of about 3 years. Environmental and familial risk factors are important predictors of IPF, but cannot alone determine who is at risk for the condition. High-resolution computed tomography is currently the best non-invasive diagnostic tool, but many efforts are now underway to identify biological markers, which may aid not only in diagnosis, but illuminate both susceptibility and progression of the disease. Although the pathogenesis of IPF remains unclear, a compelling correlation has surfaced between the mechanics of IPF and herpes virus infection, which also may lead to a biological marker for the condition. Likewise, some genetic factors have shown promise in revealing pathogenesis and possible diagnosis. The only treatment currently available to ameliorate IPF is lung transplantation, but it is a last resort effort. In terms of pharmaceutical treatment, the most significant development has been the recent approval and use of two anti-fibrotic drugs, pirfenidone and nintedanib, that appear to slow the progression of the disease, but do not eliminate the fibrotic condition that impairs patients’ breathing. As efforts progress in addressing affirmative treatments for IPF, there is consensus that not enough is being done to address palliative and psychological needs of IPF. In sum, a review of the current literature suggests tremendous accomplishments have made in treating what remains a fatal condition, but much work remains to truly understand how and why IPF occurs, and whether, short of lung transplantation, there are treatments that can improve, not just maintain, patients’ health.

Abstract Fibrotic pulmonary and pleural disorders represent a group of intrathoracic disorders with different etiologies and prognoses. A prominent part of both pulmonary and pleural fibrotic disorders remains etiologically unknown. An essential feature for all these disorders is an increase and disarray of many extracellular matrix proteins which take part in the remodeling of the fibrotic tissue. Further, the injury in pulmonary as well as in pleural fibrosis occurs often at the border between the epithelial or mesothelial and the mesenchymal cells breaking the epithelial basement membrane. Tenascin is an oligomeric matrix glycoprotein of the extracellular matrix. The best known isoforms are tenascin -C, -X, -R, -Y and -W. Tenascin-C is synthesized during embryonic development, expressed in a variety of tumors, being absent or scantily expressed in most adult tissues. The function of tenascin-C is still unclear. In lung, tenascin-C has been shown to be expressed in fetal lung during branching morphogenesis, benign and malignant lung tumors, idiopathic pulmonary fibrosis, sarcoidosis and asthma. The aim of the present study was to study tenascin-C (later called tenascin) expression in various types of pulmonary fibrosis such as usual interstitial pneumonia (UIP), desquamative interstitial pneumonia (DIP), nonspecific interstitial pneumonia (NSIP), bronchiolitis obliterans organizing pneumonia (BOOP), sarcoidosis and extrinsic allergic alveolitis as well as in fibrotic and inflammatory disorders of the pleura of different etiologies. Further, the aims were to compare the accumulation of tenascin with the prognosis in UIP, to confirm the immunohistochemical findings in UIP by Western blotting and immunoelectron miscroscopic (immuno-EM) studies, to investigate which cells synthesize tenascin in UIP and in pleural fibrosis by mRNA in situ hybridization, and to determine whether epithelial lining fluid (ELF) and serum tenascin concentration are increased in patients with UIP, sarcoidosis and extrinsic allergic alveolitis. Tenascin was shown to be increased by immunohistochemical studies in all types of pulmonary and pleural fibrotic disorders included in the study. In UIP, increased tenascin expression was associated with a shortened survival time of the patients. In immuno-EM, labeling for tenascin was seen within type II pneumocytes. UIP cases showed reactivity for a polypeptide of Mr = 200 000 by Western blotting. Myofibroblasts and type II pneumocytes were mainly shown to synthesize tenascin in UIP. Also in pleural fibrosis myofibroblasts, and in addition possibly mesothelial cells, were observed to be responsible for its synthesis. ELF and serum tenascin concentrations were increased in UIP, sarcoidosis and extrinsic allergic alveolitis. In conclusion, tenascin expression is increased in pulmonary and pleural fibrotic disorders, especially in newly formed fibrosis. In UIP, tenascin is actively synthesized at the sites of recent epithelial injury, suggesting that it plays an important role in the fibrogenesis in the lung.

Previous models of the pulmonary microvascular exchange system (28,29) have been restricted to the study of fluid and solute exchange between the pulmonary microcirculation, interstitial tissue space, and lymphatics. In severe pulmonary edema the capacities of the lymphatics and tissue space are exceeded. The fluid and solutes entering the interstitium from the circulation will, then, be transported Into the air space. The accumulation of fluid in the air space impairs the diffusion of gas (oxygen and carbon dioxide) between the air space and blood circulation; if this fluid accumulation is excessive a patient's health may be compromised. In this thesis severe pulmonary edema is studied by including the air space as a fourth compartment into the interstitial model developed by Bert and Pinder (29). A computer simulation of the four compartment (alveolar) model was developed on a digital computer. Tests of the model were made to study the effect of the parameters which were introduced into the alveolar model. These parameters include: a filtration coefficient that describes the alveolar membrane fluid conductivity, an extravascular fluid volume that represents the point at which fluid enters the air space, the alveolar fluid pressure at the onset of fluid flow into the air space, and the rate of alveolar fluid pressure change relative to an alveolar fluid volume change. For each case the dynamic response of the exchange system was recorded. In addition, two types of pulmonary edema were simulated: 1) hydrostatically induced edema, and 2) edema induced by changes to the fluid and solute permeability of the porous membrane separating the circulatory and interstitial compartments. Due to the limited data available on the interaction of the air space with the other three compartments of the pulmonary microvascular exchange system, only partial verification of the appropriate range of values of the alveolar model parameters and the predictions of the simulations was possible. The alveolar model developed in this thesis is an initial approximation but appears to provide a satisfactory approach for the inclusion of the air space in the pulmonary microvascular exchange system. / Applied Science, Faculty of / Chemical and Biological Engineering, Department of / Graduate

A preparation is described utilizing a constant flow, right-heart bypass for perfusion of the isolated main pulmonary arteries at controlled pressures. It is demonstrated that stepwise increments of pressure in the pulmonary arteries are accompanied by increases in systemic vascular resistance and in hind-limb vascular resistance. These changes were demonstrated over the whole range of 5-120 cm H₂O pressure in the pulmonary arteries. In contrast there were no significant changes in renal vascular resistance or heart rate. It is .also shown that changing the temperature of the perfusate in the pulmonary artery from 37°C to 30°C is associated with a decrease in systemic vascular resistance. The effects of raising the pulmonary arterial pressure and of cooling the pulmonary artery were abolished by cervical vagotomy. It is suggested that there is a tonic reflex vasoconstrictor tone generated by activity of receptors lying in or close to the walls of the pulmonary artery. It is further suggested that the differential effects on systemic vascular resistance and renal resistance may distribute cardiac output preferentially to the kidney providing one mechanism by which changes in blood volume may lead to appropriate changes in renal solute excretion. The later hypothesis was put to test by collecting urine from the intact kidneys of animals with isolated pulmonary pouch preparation. A step increase in the pouch pressure evoked a corresponding rise in the urinary volume, osmolar clearance, sodium excretion rate, but not the free water clearance and the potassium excretion rate. The response may be caused by renal hemodynamic changes as a result of the reflex increase in systemic arterial pressure. The rise in sodium excretion rate continued even after the release of the pressure in the pulmonary artery pouch thus the role of a natriuretic hormone in the reflex was suspected. A series of animals with one kidney intact and one kidney isolated and perfused with constant pressure was used in attempt to demonstrate the natriuretic action. These results confirmed the hemodynamic effect on the urinary function of the intact kidney. In the isolated kidney there was no statistically significant increase in sodium excretion rate, therefore the role of a natriuretic agent in the reflex response to distension of the pulmonary artery is still uncertain. / Medicine, Faculty of / Cellular and Physiological Sciences, Department of / Graduate

This study concerns a determination as to whether anaerobic organisms are involved in pulmonary diseases, particularly those of the chronic type.

The diagnosis of primary pulmonary hypertension (PPH) and prediction of its course, whether treated or untreated, presents several problems. These are of particular relevance when selection of patients for, and timing of heart-lung transplantation is being considered. I performed a retrospective study on patients with PPH and chronic large vessel thromboembolic pulmonary hypertension (TPH) seen at Groote Schuur Hospital between 1957 and 1985 in an attempt to: 1. Establish the diagnostic and prognostic value of clinical features, lung function tests, cardiac catheterisation, isotope lung scans and, in the PPH group, response to therapy; 2. Review our experience of the effects of treatment with vasodilators and oral anticoagulants, and the results of heart and lung transplantation in the PPH group; 3. Attempt to identify features which could be used to predict prognosis in PPH; and thereby 4. Define criteria for selecting PPH patients whose prognosis could be improved by heart-lung transplantation.

Includes bibliographical references / Pulmonary hypertension (PH) is defined as a rise in the pressure in the pulmonary arteries resulting from a variety of diseases including chronic infectious diseases, lung diseases and left heart diseases (LHD). It is a global health problem and accounts for a substantial portion of cardiovascular disease. PH due to LHD (PH-LHD) is credited to be the most common form of PH worldwide and is associated with adverse outcomes. Considering the suggestions of high prevalence and potential adverse outcomes of PH in sub-Saharan Africa (SSA), the investigation of the etiologies, clinical profile, correlates, and outcomes of PH-LHD in this region is a medical priority. Methods: Through a systematic review, we assessed existing evidence on the predictors of PH-LHD outcomes. Then, through two prospective multinational cohort registries, we investigated 1) the spectrum of PH in SSA; 2) the clinical profile and 6 months outcome of PH-LHD; 3) the role of electrocardiogram for diagnosing PH and 4) its prognostic role in heart failure (HF). PH was diagnosed by echocardiography in the context of clinical suspicion. Results: In high income countries, PH-LHD is almost invariably associated with increased mortality risk, but the effects on hospitalization are yet to be fully characterized. All groups of PH are found in SSA with LHD being the major cause. PH-LHD affects young people and is predominantly due to HF and rheumatic valvular heart disease. In these patients, left atrium size and tricuspid annular plan excursion are predictors of pulmonary pressures, and PH-LHD predicts short term hospitalization but not mortality. A normal electrocardiogram is very rare in patients with PH, but electrocardiogram criteria of right ventricular strain are rather rare and non-specific. Similarly, electrocardiogram abnormalities are frequent among Africans with HF, some have prognostic value for mortality risk. Conclusion: PH-LHD is the most common form of PH in SSA, with affected patients presenting with advanced disease, and it is associated with adverse outcomes. ECG abnormalities are prevalent in both PH and HF, but few of these abnormalities have prognostic value for mortality risk. Evaluating the efficacy and safety of low-cost and available drugs in reducing HF hospitalizations in PH-LHD is a key future priority. Improving early diagnosis of PH should also be encouraged.