published_or_final_version / Community Medicine / Master / Master of Philosophy

Erratum pages inserted inside back cover. / Bibliography: leaves 163-200. / xvi, 215 leaves, [13] leaves of plates : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Measurement of elastin derived peptides may be a powerful tool to evaluate mechanisms of elastin breakdown in vivo and in vitro. In human studies EDP levels may provide an early indicator of subjects undergoing increased elastin degradation that may lead to emphysema, and may serve as a biological marker of the effectiveness of therapeutic antielastases. / Thesis (Ph.D.)--University of Adelaide, Dept. of Pathology, 1994

Erratum pages inserted inside back cover. / Bibliography: leaves 163-200. / xvi, 215 leaves, [13] leaves of plates : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Measurement of elastin derived peptides may be a powerful tool to evaluate mechanisms of elastin breakdown in vivo and in vitro. In human studies EDP levels may provide an early indicator of subjects undergoing increased elastin degradation that may lead to emphysema, and may serve as a biological marker of the effectiveness of therapeutic antielastases. / Thesis (Ph.D.)--University of Adelaide, Dept. of Pathology, 1994

Thesis (MMed)--Stellenbosch University, 2015. / ENGLISH ABSTRACT: Background: The LODOX Statscan is a whole-body digital X-ray scanning device which was adapted for medical usage. The LODOX has an established role in the field of Forensic Pathology where it shows high sensitivity and specificity for the detection of skeletal pathology and foreign bodies. The role of the scanner in the detection of soft tissue pathology in the lungs of adults has not been reported and this study aims to review the radio-pathological correlation and the applicability of LODOX as a viable screening tool in the detection of lung pathology in post mortem cases. Methods: We prospectively reviewed cases which were referred for medico-legal autopsy between November 2012 and March 2013 to the Tygerberg Forensic Pathology Service mortuary, Cape Town, South Africa. All cases meeting the prescribed inclusion criteria underwent LODOX scanning as well as macroscopic and microscopic evaluation of the lungs as permitted by the Inquests Act 58 of 1959. The macroscopic and microscopic variables were considered the “gold standard” when compared with the results of the LODOX. The sensitivity, specificity, positive and negative predictive values were assessed. Results: One hundred and fifty nine cases (159) were included in the study. The most common radiographic patterns reported were the presence of ground glass opacities and consolidation. Overall, low to moderate sensitivity of these LODOX patterns in the prediction of pneumonic microscopic pathology (oedema, acute and chronic inflammation and features of diffuse alveolar damage) was noted. These values were lower than that reported for pneumonia using conventional X-rays. Additionally, these LODOX patterns have a high probability of representing oedema or autolytic/decomposition change. Pneumothorax was the most common pleural pathology detected on LODOX, but autopsy correlation could not be performed. Poor to no correlation was noted with the variables of cavity, malignant tumour, and bronchiectasis, but the prevalence of these conditions in our cohort was low. In general, LODOX predictions were better at excluding pathology which was not present rather than confirming pathology which was present. Conclusions: The LODOX offers excellent evidentiary value in the demonstration of a pneumothorax but currently has limited value as a “stand alone” test in the field of Forensic Pathology. However the continued use of the LODOX as an adjunct examination, as well as prospective study of its applicability, is advised. / AFRIKAANSE OPSOMMING: Agtergrond: Die LODOX Statscan is ‘n heel-liggaam digitale X-straal skandeer apparaat wat aangepas is vir mediese gebruik. Die LODOX het ‘n gevestigde rol in Geregtelike Patologie, waar dit ‘n hoë sensitiwiteit en spesifisiteit het in die opsporing van skeletale patologie en vreemde voorwerpe. Die rol van die skandeerder in die opspoor van sagte weefsel patologie in die longe van volwassenes is nog nie gerapporteer nie, en hierdie studie ondersoek die radio-patologiese korrelasie en toepaslikheid van LODOX as ‘n doeltreffende siftingsmeganisme om long patologie op te spoor in post-mortale gevalle. Metode: Gevalle wat verwys is na die Tygerberg Geregtelike Patologie Diens lykshuis in Kaapstad, Suid-Afrika vir medies-geregtelike outopsies tussen November 2012 en Maart 2013, is prospektief geëvalueer. Alle gevalle wat die voorgeskrewe insluitingskriteria nagekom het, het LODOX skandering asook makroskopiese en mikroskopiese ondersoek van die longe ondergaan, soos toegelaat deur die Wet op Geregtelike Doodsondersoeke Nr 58 van 1959. Die makroskopiese en mikroskopiese veranderlikes is beskou as die “goud standaard” in vergelyking met die resultate van die LODOX. Die sensitiwiteit, spesifisiteit, positiewe en negatiewe voorspellingswaardes is beoordeel. Resultate: Eenhonderd-nege-en-vyftig gevalle (159) is ingesluit in die studie. Die algemeenste radiografiese pattroon wat gerapporteer is, was die teenwoordigheid van gemaalde glas opasiteit en konsolidasie. In geheel is lae to matige sensitiwiteit van hierdie LODOX beelde waargeneem in die voorspelling van pneumoniese mikroskopiese patologie (edeem, akute en chroniese ontsteking, en eienskappe van diffuse alveolêre skade). Hierdie waardes was laer as die wat gerapporteer is vir pneumonie met konvensionele X-strale. Verder het hierdie LODOX beelde ‘n hoë waarskynlikheid om edeem en/of outolise/ontbinding uit te beeld. Pneumotoraks was die algemeenste pleurale patologie wat waargeneem is met die LODOX, maar outopsie korrelasie kon nie gedoen word nie. Swak tot geen korrelasie is gemerk vir die veranderlikes kaviteit, maligne tumor en brongi-ektase, maar die prevalensie van hierdie toestande in ons kohort was laag. Oor die algemeen was LODOX voorspellings beter om patologie wat nie teenwoordig is nie, uit te skakel, eerder as om patologie wat teenwoordig is, te bevestig. Gevolgtrekking: The LODOX is ‘n uitstekende bewysstuk in die aantoon van ‘n pneumotoraks, maar huidiglik het dit beperkte waarde as onafhanklike toets in die veld van Geregtelike Patologie. Desnieteenstaande word die verdere gebruik van LODOX as bydraende ondersoek, sowel as die prospektiewe studie van sy toepaslikheid aanbeveel.

[Truncated abstract] Urinary desmosines have been proposed as a biomarker for inflammatory lung damage. Desmosine, a breakdown product of elastin, is an effective marker of the degradation of elastin and has been studied in many disease scenarios where there is acute and chronic lung inflammation. Lung matrix degradation has been proven in vitro and in vivo with many experiments showing that the excess proteases degrades lung matrix. The secretion of proteases by neutrophils is an innate response of the body to the invasion by micro organisms and when secreted in excess, the protective anti-protease mechanism is swamped. Chronic inflammation and persistent infection eventually leads to bronchiectasis and respiratory failure. Urinary desmosine has been shown to be elevated in respiratory conditions with acute and chronic inflammation . . . Urinary desmosine levels in a large cohort of healthy children have been established using this method and predictive Z-score formulae have been developed to use in children with lung disease. Exploration of these scores in children with CF have shown that the levels of urinary desmosine appear to be sensitive to the clinical setting, where high urinary desmosine levels were present during exacerbation and significantly reduced when treated for infection with antibiotic therapy and physiotherapy. The study of young children under the age of seven was undertaken to determine if the urinary desmosine levels could indicate when lung damage was occurring and to determine what mechanisms might be involved. Since there appeared to be no apparent relationship between elevated desmosines and proteases in the lung in young children with CF, further studies are required to define the mechanisms behind increased elastin metabolism in those children.

[Truncated abstract] Respiratory system impedance (Zrs) is commonly measured at low to medium frequencies (0.5 - 40 Hz) to infer structural and physiological information about the respiratory system. Coupled with the use of mathematical models of the lungs, Zrs has been used to partition the behaviour of the conductive airways and the respiratory tissues. High-frequency (HF) Zrs beyond 100 Hz has been comparatively less studied and understood. Past work has revealed spectral features at high frequencies termed antiresonances, marked by peaks in the real part of Zrs, often coinciding with zero-crossings in the imaginary part. It has been shown that the first occurrence of antiresonance in humans primarily reflects the contribution of the airways, and is a property of sound wave propagation in the airways. Also, the first antiresonance is altered in diseases such as chronic airflow obstruction, and wheeze in infants. The main aim of this project is to shed further understanding about the first antiresonance, via the behaviour of two parameters characterising this feature of the HF spectrum: the frequency at which the first antiresonance occurs, far,1, and the magnitude of the real part of Zrs at this frequency, Rrs(far,1). In our studies, Zrs is measured as an input impedance using the forced oscillation technique with a loudspeaker-in-box and wavetube setup, and employing pseudorandom frequency signals. We studied the effects of altered lung conditions, first in an animal model, then progressed on to humans. v vi In the rat, we found that both far,1 and Rrs(far,1) tended to decrease together with increasing lung volume. With methacholine(MCh)-induced bronchoconstriction, rats showed increases in far,1 and Rrs(far,1) with increasing MCh dose, but these occurred at higher doses compared to increases in airway resistance. The changes in these HF parameters were independent of the changes in tissue properties. ... It was found that in a group of patients with emphysema, VDRrs(far,1) was significantly more negative, potentially due to alterations to airway dimensions and wall properties. Furthermore, VDRrs(far,1) was correlated with extent of obstruction and hyperinflation, suggesting a relationship with severity of emphysema. These results show that the first antiresonance reflect changes in the airways, and its measurement shows promise as a clinical tool, in its potential as an easy-to-perform assessor of conditions in which the airways are altered. Keywords: antiresonance, respiratory input impedance, high frequencies, emphysema

Thesis (PhD (Medicine. Internal medicine))--University of Stellenbosch, 2007. / 1.1. Background Tumors arising from the lung, pleura, or chest wall are a frequent problem in clinical pulmonary medicine. Most lesions are either infectious, neoplastic or granulomatous in nature, but a variety of other differential diagnoses must be considered. An accurate diagnosis is important because the available treatments differ substantially, and because any delay will impair the prognosis in potentially curable patients with lung carcinoma. The investigations involve the disciplines of radiology, pulmonology, surgery, microbiology, and anatomical pathology and consume a respectable amount of resources. The aim of the work covered in this thesis was to optimize the available diagnostic methods for the routine use in a health care setting with limited resources. 1.2. Methods The general idea of this work was to identify conventional sampling methods that could be developed further to become more useful for the diagnosis of chest tumors in a low resource health care setting. The key method was research performed: a) to revise and expand the indication for a sampling method, b) to technically improve the sampling process, and c) to optimize sample transport, preparation and analysis in collaboration with the analytical laboratory. 1.3. Results A list of invasive diagnostic procedures, imaging methods and analytical processes were developed, evaluated and integrated into clinical practice. A) transbronchial needle aspiration, B) transthoracic cutting needle biopsy, C) transthoracic fine needle aspiration, D) transthoracic ultrasound, and E) rapid on-site evaluation of needle aspirates by a cytopathologist. Five studies pertaining to this thesis were published in international peerreviewed journals: â ¢ Safety and yield of ultrasound-assisted transthoracic biopsy performed by pulmonologists (Respiration 2004;71:519-22) This paper established that ultrasound-assisted transthoracic biopsy performed by pulmonologists is feasible, safe, practical, low-cost and has a high yield. â ¢ Utility of rapid on-site evaluation of transbronchial needle aspirates (Respiration 2005;72:182-8) This paper demonstrated the economical advantages of on-site evaluation of transbronchial specimens in a low-resource setting. â ¢ Transbronchial needle aspirates: comparison of two preparation methods (Chest 2005;127:2015-8) This paper demonstrated that preparing smears on-site has a far better yield than pooling samples into a vial. This means that the yield is improved over the current standard at no additional cost. â ¢ Transbronchial needle aspirates: how many passes per target site? (European Respiratory Journal 2007;29:112-6) This paper investigated the most economical and effective approach to serial sampling with transbronchial needle aspiration during flexible bronchoscopy. â ¢ Ultrasound assisted transthoracic biopsy: fine needle aspiration or cutting needle biopsy? (European Respiratory Journal 2007;29:357-62) This paper compared two common methods of sampling and demonstrates that the less expensive method is sufficient in the majority of cases. 1.4. Conclusion This work has impacted on current practice in multiple ways. Conventional methods have been optimized by improving technical factors and with the integration of interdisciplinary collaboration. The initiated research is ongoing with the aim to achieve continued technical and economical improvements in the diagnosis of chest tumors.

Liu Kin Hang. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (leaves 88-98). / Abstracts in English and Chinese. / Abstract (in English) --- p.i / Abstract (in Chinese) --- p.iii / Acknowledgement --- p.v / Table of Contents --- p.vi / List of Tables --- p.ix / List of Figures --- p.x / Glossary of Terms and Abbreviations --- p.xi / Chapter Section I: --- Overview --- p.1 / Chapter Chapter 1: --- Introduction --- p.2 / Chapter 1.1 --- Asthma and Assessment of A irway Inflammation --- p.2 / Chapter 1.1.1 --- Assessment of A irway Inflammation --- p.4 / Chapter 1.1.2 --- Invasive and Noninvasive Methods --- p.4 / Chapter 1.1.3 --- Exhaled Nitric Oxide as a Diagnostic Marker and Its Correlation with Other Markers of Inflammation --- p.6 / Chapter 1.1.4 --- Normal Reference Studies of Exhaled Nitric Oxide --- p.8 / Chapter 1.2 --- Aim of Study --- p.10 / Chapter Chapter 2: --- Plan of Study --- p.11 / Chapter Section II: --- Literature Review --- p.13 / Chapter Chapter 3: --- Nitric Oxide Biology --- p.15 / Chapter 3.1 --- Exhaled Nitric Oxide Production in Airway --- p.15 / Chapter 3.2 --- Nitric Oxide Production and Function --- p.16 / Chapter 3.3 --- Nitric Oxide Synthase Pathway --- p.18 / Chapter 3.4 --- Factors Affecting Exhaled Nitric Oxide Level --- p.21 / Chapter 3.4.1 --- Procedure-related Factors --- p.22 / Chapter 3.4.1.1 --- Nasal Nitric Oxide Contamination --- p.22 / Chapter 3.4.1.2 --- Exhalation Procedure 226}0´ؤؤStarting Lung Volumes --- p.23 / Chapter 3.4.1.3 --- Exhalation Procedure 226}0ؤ Flow --- p.23 / Chapter 3.4.1.4 --- Circadian Rhythm --- p.25 / Chapter 3.4.2 --- Patient Factors --- p.26 / Chapter 3.4.2.1 --- Sex --- p.26 / Chapter 3.4.2.2 --- Upper Respiratory Tract Infection --- p.26 / Chapter 3.4.2.3 --- Diet and Exhaled Nitric Oxide --- p.27 / Chapter 3.4.2.4 --- Effect of Spirometry and Exercise --- p.28 / Chapter 3.4.3 --- Environmental Factors --- p.28 / Chapter Chapter 4: --- Exhaled Nitric Oxide in Asthmatics and Its Relationship to Anti-inflammatory Treatment --- p.31 / Chapter Chapter 5: --- Relationship of Exhaled Nitric Oxide with Other Inflammatory Markers --- p.33 / Chapter 5.1 --- Correlation of Findings from Biopsy and Bronchoalveolar Lavage with Exhaled Nitric Oxide --- p.33 / Chapter 5.2 --- "Exhaled Nitric Oxide, Induced Sputum Analysis and Sputum Eosinophil Cationic Protein" --- p.35 / Chapter Section III: --- Original Study --- p.37 / Chapter Chapter 6: --- Methodology --- p.38 / Chapter 6.1 --- Study Population --- p.38 / Chapter 6.2 --- The International Study of Asthma and Allergies in Childhood --- p.40 / Chapter 6.3 --- ISAAC Questionnaires --- p.42 / Chapter 6.4 --- Standardized Approach for Answering Questions in the Field --- p.44 / Chapter 6.5 --- Anthropometric Measurements --- p.45 / Chapter 6.6 --- Exhaled Nitric Oxide Measurement --- p.46 / Chapter 6.6.1 --- "NIOY® (Aerocrine AB, Stockholm, Sweden)" --- p.46 / Chapter 6.6.2 --- Calibration Procedures --- p.47 / Chapter 6.6.3 --- Exhaled Nitric Oxide Measurement --- p.48 / Chapter 6.7 --- Classification of Subjects --- p.51 / Chapter 6.8 --- Statistical Analysis --- p.53 / Chapter Chapter 7: --- Results --- p.54 / Chapter 7.1 --- Subjects and Demography --- p.54 / Chapter 7.2 --- Exhaled Nitric Oxide in Chinese Children --- p.58 / Chapter 7.3 --- Exhaled Nitric Oxide in Caucasians and Other Ethnic Groups --- p.66 / Chapter Chapter 8: --- Discussion --- p.69 / Chapter Chapter 9: --- Conclusion and Further Studies --- p.76 / Appendix 1 Questionnaires (Chinese Version) --- p.80 / Appendix 2 Questionnaires (English Version) --- p.84 / References --- p.88

In developing countries, acute respiratory infections (ARIs) are responsible for two million deaths per year. Most victims are children who are less than 5 years old. Pneumonia kills 5000 children per day. The statistics for cardiovascular diseases (CVDs) are even more alarming. According to a 2009 report from the World Health Organization (WHO), CVDs kill 17 million people per year. In many resource-poor parts of the world such as India and China, many people are unable to access cardiologists, pulmonologists, and other specialists. Hence, low skilled health professionals are responsible for screening people for ARIs and CVDs in these areas. For example, in the rural areas of the Philippines, there is only one doctor for every 10,000 people. By contrast, the United States has one doctor for every 500 Americans. Due to advances in technology, it is now possible to use a smartphone for audio recording, signal processing, and machine learning. In my thesis, I have developed an Android application named Smart Auscultation. Auscultation is a process in which physicians listen to heart and lung sounds to diagnose disorders. Cardiologists spend years mastering this skill. The Smart Auscultation application is capable of recording and classifying heart sounds, and can be used by public or clinical health workers. This application can detect abnormal heart sounds with up to 92-98% accuracy. In addition, the application can record, but not yet classify, lung sounds. This application will be able to help save thousands of lives by allowing anyone to identify abnormal heart and lung sounds.