Sepsis is a life threatening condition caused by infectious agents, including the Gram-positive bacterium Staphylococcus aureus. Symptoms of sepsis often include intravascular coagulation and organ failure. Tissue factor (TF), the initiator of coagulation, may contribute to fibrin deposition in the lungs of patients with sepsis. We have found that lung epithelial cells constitutively express TF on the cell surface and in intracellular pools. Levels of TF diminished in response to S. aureus invasion possibly indicating a release in the form of shedding vesicles. TF levels diminish in response to viable bacteria, but not in response to heat killed (HK) bacteria. Our studies indicate that bacterial attachment at the host cell surface is insufficient to diminish levels of constitutive TF. Finally, we established that levels of constitutive intracellular TF diminish in response to the bacterial toxin, α-hemolysin, alone. This approach may provide a basis for understanding the role of TF in coagulation seen in sepsis. / Department of Biology

Weight loss and depletion of fat-free mass commonly occurs in patients with COPD. The objective of the study was to determine the magnitude and duration of protein depletion during an episode of acute exacerbation. Fifteen patients (9 women and 6 men) admitted for an acute exacerbation of COPD participated in a descriptive study that prospectively measured individual nitrogen balance over a 6-week follow-up period using repeated nitrogen balance tests. / The mean nitrogen balance in hospital was -13.20 +/- 11.63 g N/day. Only 2 patients achieved a positive nitrogen balance by 2 weeks post-admission and 4 more patients by 4 weeks post-admission. At 6-weeks post-admission, 7 patients (47%) were still in negative nitrogen balance (-10.75 +/- 9.34 g N/day). Protein and energy intakes were significantly higher in patients who achieved a positive nitrogen balance (1.7 +/- 0.5 g protein/kg/day and 120 +/- 30% of estimated energy expenditure (1.7 x REE)) than patients who remained in a negative nitrogen balance (1.3 +/- 0.6 g protein/kg/day and 70 +/- 20% of estimated energy expenditure). There were no significant changes in weight or handgrip strength over the follow-up period. No effect of cumulative or daily corticosteroid doses on nitrogen balance or changes in handgrip strength were found. / In conclusion, the catabolic stress of an acute exacerbation on nutritional status is remarkable. Patients admitted for an acute exacerbation of COPD are in severe negative nitrogen balance, which improves very slowly post-discharge. A negative nitrogen balance is prolonged in patients who have a decreased protein and energy intake.

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.

No description available.

Lung disease is the third leading cause of death worldwide. The only curative intervention for end-stage lung disease is lung transplantation, which remains limited by the shortage of viable donor organs. Strategies to improve outcomes for patients with end-stage lung disease include: (i) ex vivo recovery of initially unusable donor lungs to a level suitable for transplantation, and (ii) repair of damaged lungs in situ to avoid the need for transplantation. Recovery of damaged lungs both ex vivo and in situ necessitates precise regulation of the lung extracellular environment, which includes biochemical, physical, and mechanical stimuli across scales. This thesis describes the development of bioengineering tools, including bioreactors and biomaterials, that leverage the lung extracellular environment across cellular, tissue, and organ scales to: (i) recover whole injured donor lungs ex vivo, (ii) assess and repair regional lung tissue injury in situ, and (iii) study the pathological cellular microenvironment in cystic fibrosis. In Chapter 1, regulation of the organ macroenvironment (ventilation, perfusion, systemic metabolism) with a homeostatic cross-circulation bioreactor enabled up to 100 hours of ex vivo lung support and recovery of injured human donor lungs. In Chapter 2, quantitative analysis of localized lung tissue properties, including lung sounds, enabled detection and assessment of pulmonary air leak, and recapitulation of lung microenvironmental features (structure, mechanics, composition) in a therapeutic biomaterial sealant enabled rapid treatment of air leaks. In Chapter 3, the first quantitative characterization of the cystic fibrosis matrisome (matrix proteome) identified pathological alterations to the microenvironment, and investigated implications for inflammation and immunity in cystic fibrosis. Collectively, these studies demonstrate that macro- and microenvironmental signals, including ventilation and perfusion mechanics, homeostatic metabolic regulation, and extracellular matrix structure and composition, can be leveraged to reveal previously unknown drivers of disease and promote recovery and repair of damaged lungs.

No description available.

Thesis (MScPhysio)--Stellenbosch University, 2008. / ENGLISH ABSTRACT: Acute exacerbation is an important event of COPD as it causes significant disability and mortality. Especially repeated hospitalisation of patients with acute exacerbation has been associated with reduce quality of life and excessive hospitalisation cost. Chronic Obstructive Pulmonary Disease causes significant functional limitations that translate into enormous economic and societal burden. Study Aim: To describe the profile and selected outcomes of Chronic Obstructive Pulmonary Disease (COPD) patients admitted with acute exacerbation to hospitals in the northern suburbs of the Western Cape. Study design: A multicenter retrospective descriptive single subject design was used. Method: Patients admitted with the diagnosis of COPD with acute exacerbation in the time period 01June 2004-01June 2005 were followed up retrospectively for a period of 12 months. The demographics, medical condition on admission and past presentation of acute exacerbation, length of stay in hospital and the number of readmissions for acute exacerbation in the 12 month period were collected and recorded on a self designed data capture sheet. Results: One hundred and seventy eight patients were admitted with acute exacerbation at the three hospitals. The mean age of the patients were 63 (±11.73), more males than females (103: 75) were admitted. Subjects spent a mean of 5.67 (±6.55), days in hospital with every admission and admission frequency of up to eight periods were recorded. Of the n=178 admitted, 56% had one admission and 44% had 2 or more admissions in the study year. This resulted in a total of 338 hospital admissions with the 78 subjects responsible for the majority of admissions (238) Subjects presenting with two or more co-morbidities had a significantly greater risk of multiple re admissions. Subjects with three or more admissions had two or more co morbidities (p=0.001), comparatively those with one admission had only one co morbidity. Congestive cardiac failure (p=0.01) as well as the lack of Long Term Oxygen Therapy p=0.017) were associated with increase risk of three or more admissions. Conclusion: Patients admitted with acute exacerbation to the hospitals where the study was conducted presented with an age ranging from 30-95 years. Patients with 2 or more admissions experience up to eight readmissions episodes in the study year. This is a cause of concern in respect of the burden of disease on especially the younger economically viable South African population. In the current study factors that influenced readmission were the presence of two or more co morbid diseases, specifically the presence of congestive cardiac failure as well as the lack of LTOT. Interventions including a pulmonary rehabilitation programme post discharge should be aimed at decreasing frequency of hospitalisation especially in those patients who are a risk of readmission. / AFRIKAANSE OPSOMMING: Verergering van simptome in Kroniese Obstruktiewe Lugweg Siekte (KOLS) is baie belangrik as gevolg van die ongeskiktheid en mortalitieit wat dit veroorsaak. Dit veroorsaak vermindering in die kwaliteit van lewe en verhoog hospitaal koste verbind met die siekte. Die beperkings toe te skrywe aan die Kroniese Obstruktiewe Lugweg Siekte veroorsaak ontsettende ekonomiese en sosiale druk. Doelstelling: Om die profiel en geselekteerde uitkomste van pasiente met Kroniese Obstruktiewe Lugweg Siekte toegelaat met verergering in die hospitale van die noordelike voorstede van die Wes Kaap te beskryf. Studie ontwerp: ʼn Multisentrum retrospektiewe beskrywende enkel persoon studie. Studie metode: Pasiente toegelaat met verergering van Kroniese Obstruktiewe Lugweg Siekte in die periode 01Junie 2004-01Junie 2005 was retrospektief opgevolg vir ‘n periode van 12-maande. Demografiese data, mediese toestand op toelating en ontslag, lengte van hospitaal verblyf en getal toelatings in die 12- maande was gekollekteer en gedokumenteer op self ontwerpde vorms. Resultate: Een-honderd agt en seventig pasiente was toegelaat met verergering by die drie hospitale. Die gemiddelde ouderdom van die studie populasie was 63 (±11.73) met meer mans as vrouens (103: 75) toegelaat. Die studie populasie het gemiddelde dae van 5.67 (±6.55), in die hospitaal deurgebring en toelating frekwensie van agt episodes was gedokumenteer. Van die n=178 toegelaat was 56% eenkeer toegelaat en 44% het 2 of meer toelatings in die studie jaar gehad. Dit het in 338 hospital toelaatings veroorsaak en 78 van die studie populasie verantwoordelik vir die meeste van die toelatings (238). Die groep met drie of meer toelatings in die studie jaar het twee of meer siektetoestande (p=0.001) gehad, teenorgesteld met die wat net een toelaat was met een siektetoestand. Hart versaaking (p=0.01) en die gebrek aan suurstof by die huis (p=0.017) was verbind met meer risiko van drie of meer toelating. Samevatting: Die ouderdoms verskil was wydbeskrywend van 30-95 jaar van die pasiente wat in die studie jaar toegelaat is by die drie hospitale. Pasiente wat 2 of meer keer toegelaat is het tot agt hertoelatings in die studie jaar gehad. Kommerwekkend is die uitwerking van die siekte op die jonger werkend populasie in Suid Afrika. In die studie was hertoelating beinvloed deur die teenwoordigheid van twee of meer siektetoestande, spesifiek hart versaaking sowel as die gebrek aan suurstof by die huis. Intervensies insluitende pulmonale rehabilitasie na ontslag se doel moet wees om vermindering van heraaldelike hospitalisasie in hoë risiko pasiente vir hospitalisasie.

published_or_final_version / Social Work / Master / Master of Social Work