The purpose of this thesis is to illustrate the author's observations on radiological investigations of the right lung both in the living body and at post-mortem, and to describe certain aspects of anatomical, clinical, pathological and radiological interest.

Objective Several studies have shown that serum copper concentrations are higher in various carcinomas when compared to a healthy population; owing to their role as an inflammatory marker. Zinc acts as a cellular growth protector and it has been demonstrated that its deficiency is involved in several stages of malignant cell transformation. However, the usefulness of the serum zinc and copper determinations in cancer prevention, detection, treatment monitoring and prognosis require further investigation. The aim of this study is to demonstrate the diagnostic and prognostic significance of serum zinc levels (SZL) and serum copper levels (SCL), and the copper/zinc (Cu/Zn) ratio, in non-small cell lung cancer (NSCLC). Materials and Methods Thirty-four patients with NSCLC were prospectively identified, prior to treatment, over a period of one calendar year (February 2003 - January 2004) at the Department of Radiation Oncology, Johannesburg General Hospital (now Charlotte Maxeke Johannesburg Academic Hospital) and the University of the Witwatersrand. SCL and SZL were measured using atomic absorption spectroscopy (AAS) and the Cu/Zn ratio was calculated. Results SCL shows an increase (mean SCL were 0.66mg/L, 0.74mg/L and 0.76mg/L for stage II, III and IV respectively) (P=0.0897); and SZL shows a decrease (0.70mg/L,0.63mg/L and 0.62mg/L for stage II, III and IV respectively) (P=0.199) with advancing stage. The levels of both these trace elements are much lower than the reference range for a normal population. The Cu/Zn ratio increases with stage (0.995, 1.308 and 1.441 for stage II, III and IV respectively). The results were not statistically significant, but a definite trend could be observed. In addition, marked differences were noted between early stages (II) and advanced stages (III and IV) of the disease. Conclusion The lower levels of both trace elements, when compared to a reference range, are an indication of the low levels of immunity and poor general condition of patients with NSCLC (with particular reference to the author‟s institution). A clear trend could be demonstrated of increasing SCLs and decreasing SZLs with progressive stages in NSCLC. The Cu/Zn ratio also reflects similar findings in relation to stages of the disease. The results were not statistically significant, although this can be attributed to a small sample size. While trace element levels and the Cu/Zn ratio cannot be advocated as a tumour marker and prognostic variable for NSCLC at present, they do merit further study, especially in a resource constrained environment, as a simple and inexpensive diagnostic and prognostic test.

A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in partial fulfillment of the requirements for the degree of Master of Medicine in Community Health (Occupational Medicine) Johannesburg, March 2017. / Introduction: The Occupational Diseases in Mines and Works Act (ODMWA) 1973 (as amended in 2002) provides for compensation of occupational lung diseases in living and deceased miners and ex-miners. Certification data constitute a valuable source of information on occupational diseases in the mining industry. Objectives: The objectives of the study were: i) To describe the extent and type of compensable lung diseases in South African mining from 2004-2012, by commodity; ii) to describe certification trends over 2004-2012; iii) to examine specific issues related to some of the compensable occupational lung diseases (including service duration in coal miners with coal workers’ pneumoconiosis by coal type, describe asbestos related diseases in women and number of miners with exclusive diamond miners certified with mesothelioma during this period); iv) to determine the odds of developing mesothelioma from chrysotile mining and other associated risk factors and v)to determine time from the certification to compensation payment, using a proportion of cases certified in 2009, 2010 and 2011 financial years. Methods: A descriptive analysis was conducted using the Medical Bureau of Occupational Diseases (MBOD) dataset using claims from living miners, certified from 2004 up to 2012, certified with compensable disease, for the first three objectives. For the fourth objective, the MBOD database was used to select diseases with considerable numbers from the 2009, 2010 and 2011 years. A ten percent sample of each disease group was selected through random sampling using stata 12, to determine time to compensation, joined with Commission for Compensation of Occupational Diseases (CCOD) compensation database. Stataversion 12 was used to clean and analyse data. For the fifth objective, a case control analysis was conducted to estimate the risk of mesothelioma from miners with exclusively chrysotile mining, using exposure data from an external database. Results: There were67660 compensable disease certifications from 2004 to 2012 financial years, in living current and ex-miners. Almost 62% of the certification outcomes for compensable diseases were from tuberculosis alone, comprising of current, first and second degree TB. First and second degree diseases with no tuberculosis comprised 27% and 1.3% respectively. There were 6601 diseases (9.7%) certified as second-degree with tuberculosis. The proportion of specific diseases other than tuberculosis comprised of silicosis (14%); silico-tuberculosis (9%);obstructive airways disease (2.2%);coal workers’ pneumoconiosis (0.5%); asbestos pleural disease (6.7%) ; asbestos interstitial disease (5.2%); mesothelioma (0.2%); lung cancer (0.04%) and 0.1% were from other diseases. Females contributed 3.8% to the disease burden while black miners had 92%. Twenty five percent of the compensable diseases were from ex-miners and 49 179from active miners. Although 63% of compensable diseases were from unknown commodity (missing), 30% were from gold mining. The certification trends for pneumoconiosis and tuberculosis peaked in 2008, with statistically significant trend for asbestosis (p=0.01) and silico-TB (P=0.038). Examination of the specific issues showed no statistically significant difference between CWP certification from anthracite and bituminous coal ranks with regards to service duration, silicosis was certified in 544 platinum miners but none of them had exclusively platinum mining. Asbestos related disease was certified in 2241 women, with 55.4% being pleural disease in the first degree and none of the certified women were younger than 30 years of age, and the average service duration was approximately seven years (mean=6.97 years, SD 6.37 years). From the sample of 389 certified cases, 26.5% (n=103) were certified at the end of the 2012 financial years. The mean time to compensation 38 months, 36 months and 19.4 months for 2009, 2010 and 2011 financial years respectively. The case-control analysis found no statistically significant association between chrysotile mining and mesothelioma from univariate analysis (OR=2.0 p>0.05; 95% CI: 0.7-5.4); as well as multivariate analysis (OR=1.5; p>0.05; 95%CI: 0.4-5.2) compared to the reference group. Conclusion:The burden of occupational lung diseases in living current miners and ex-miners is high, mainly from tuberculosis during this period, irrespective of the commodity and population group. A significant finding from this study was the significant proportion of miners certified with pneumoconiosis with less than fifteen years of mining service. The number of women certified during this period was mainly from asbestos related diseases, a far lesser number of women were certified with disease from other commodities. The findings from this study support what was reported in literature namely; unacceptably long time to compensation; incomplete documentation of exposure history in the form of service records and no established risk for mesothelioma from exclusive chrysotile miners. / MT2017

Diss. (sammanfattning) Uppsala : Univ., 2003. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 5 uppsatser.

No description available.

Research report in partial fulfillment for the degree of MMed (Pulmonology), faculty of Health Sciences, University of the Witwatersrand / Introduction: cancer remains the most common malignancy, with an estimated 1.04 million new cases each year worldwide, accounting for 12.8% of new cancer cases. Of these cases, 58% occur in the developing world. Lung cancer is the most common cancer among men, with an incidence of approximately 37.5 new cases per million. The incidence is lower in women, at 1.08 cases per million population. Lung cancer is the leading cause of morbidity and mortality in the world. There is evidence in the literature of racial and gender differences in the distribution of lung cancer. However data from South Africa is sparse. Aim: The primary objective of this study was to investigate whether differences existed in demographic and histological features of lung cancer when comparing black versus white patients with cancer of the lung in Johannesburg Methods: A retrospective case record review of 817 patients presenting to the pulmonology units of the three hospitals, between January 1992 and December 1998, was undertaken. Demographic, clinical, laboratory and histological features were captured and analyzed, using the GraphPad InStat 3.10 program for Windows. The histological cell types of lung cancer were characterized using the 1981 WHO classification. Results: A total of 817 patients with lung cancer were enrolled in the study. The age group of the total sample ranged between 26-92 years with a mean±SEM of 61.0±0.04 years. There were 574 (70.3%) male patients versus 222 (27.2%) female patients. The remaining 21 (2.6%) patients had no data recorded with respect to their gender. The racial stratification of these patients in decreasing order of frequency was whites 441 (54.0%), blacks 337 (41.3%), mixed race 24 (3.0%) and Indians 15 (1.8%). The study group consisted of the 778 black and white patients. The black patients were younger (mean ±SEM, 57.3±0.5years) than the white patients (mean ±SEM, 64.0±9.9) irrespective of gender (p <0.001). Overall 632 patients were smokers, either current or ex-smokers. The amount of cigarettes consumed was significantly higher in white patients compared to black patients (mean pack years for white patients was 52.7 ± 27.1 versus 21.7± 14.3 pack years for black patients (p <0.001)). This difference was irrespective of gender. The mode of diagnosis in the 778 lung cancer patients was bronchoscopy in the majority 479 (54.0%), followed by sputum cytology in 152 (18.3%) and fine needle aspiration in 105 (12.7%). Tissue biopsy was utilized to diagnose 23 (2.7%) of the lung cancers. In some cases more than a single modality of diagnosis was utilized. The radiological features of the 778 lung cancer patients varied. The majority had a mass on chest radiograph; a lung mass in 357 (46.5%) patients, a hilar mass in 166 (21.6%), and a mediastinal mass in 18 (0.3%) patients. Pleural effusions were found in 82 (10.7%), lung atelectasis in 78 (10.2%), an infiltrate in 29 (3.8%) and consolidation in 25 (3.3%). Histological cell types of lung cancer in the 778 patients consisted of the following, in descending order of frequency; squamous cell carcinoma in 341 (43.8%), adenocarcinoma in 167 (21.5%), small cell carcinoma in 129 (16.6%) and large cell carcinoma in 68 (8.7%) of the cases. Other histological cell types accounted for 73 (9.4%) of the patients. Small cell carcinoma was overall more common amongst white patients especially males and in black patients it was exclusively in females (p<0.0005). However the black female patients tended to have more small cell carcinoma (40 (45.5%)), compared to the white female patients who had more squamous cell carcinoma (54 (45.0%)) in the majority. There was a small proportion of patients considered to be operable with intent to cure -74 (9.5%). This was a poor operability rate compared to an expected operability rate of 15-20%. This rate was as distressing when divided along racial lines; 29 (8.6%) of black patients and 45 (10.2%) of white patients being considered operable. Discussion: The demographics of the study group were different. The black patients tended to be significantly younger and smoked less cigarettes compared to the white patients. There was a significantly greater number of male patients with lung cancer than female patients. This difference was irrespective of race. The ranked frequency of histological subtypes was similar in both race groups. However, the black female had more small cell carcinoma, compared to white females with a preponderance of squamous cell carcinoma. The operability of all lung cancer patients, irrespective of gender and race, was dismal at 9.5%, compared to the standard norm of 15-25% operability rate. This is worrying when one considers the fact that surgery is the means to a cure. It either suggests there is a delay in seeking medical care and/or the lack of medical resources to permit screening and early diagnosis of the malignancy. Conclusions: This study did not demonstrate any ranked frequency differences in histological cell type distribution between black and white patients. Squamous cell carcinoma was the most common histological cell type regardless of race. Small cell carcinoma was significantly more common among white patients, especially the males while among the black patients it was exclusively found in the females. Black patients with lung cancer tended to present at an earlier age. Black females were less likely to develop lung cancer when compared with the white females. The black patients smoked fewer cigarettes than the white patients irrespective of gender. The operability of our patients, in the study, was poor in all race groups.

Peru is a South American nation with a growing and aging population of 31 million people with a life expectancy at birth of 76.7 years. The country is divided into 25 regions, 79% of the population is urban, and Lima, the capital, concentrates more than a third of the population.1 Although Peru is an upper-middle-income country, health expenditure represents only 5.1% of the gross domestic product, which is lower than the average of Latin America and the Caribbean (LATAM) (8.56%).2 Out-of-pocket health expenditure is 30.9%.3 Peru has a comprehensive National Cancer Plan and two population-based cancer registries in Lima and Arequipa. / Revisión por pares

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Lung transplantation is a life-saving therapy for patients suffering from end-stage lung disease; however, the majority of donor lungs are injured and attempts to transplant them results in a high risk of primary graft dysfunction in the recipient, a type of severe acute lung injury. Previously, a novel method of lung preservation known as ex vivo lung perfusion (EVLP) has been developed in which donor lungs are continuously perfused and ventilated at normothermia using a protective strategy. Donor lungs have been shown to tolerate at least 12 h of preservation in this manner without the accrual of injury. Hence, EVLP could act as a platform on which injured donor lungs could potentially be evaluated and repaired. To explore this concept, we utilized interleukin-10 (IL-10), an anti-inflammatory cytokine, as a prototypical drug for ex vivo delivery. Because IL-10 protein has a prolonged half-life during EVLP, we delivered recombinant IL-10 by the intravascular and intratracheal routes to clinically-rejected injured human lungs. Intratracheal delivery resulted in elevated levels of IL-10 in both tissue and perfusate whereas intravascular delivery resulted in elevated levels of IL-10 only in the perfusate over 12 h of EVLP. There was, however, no beneficial effect to either lung function or lung inflammation. This was thought to be a result of intratracheally delivered IL-10 leaking out into the perfusate where it may not be biologically active. Constant IL-10 production within the lung tissue could be achieved using a gene therapy approach. Thus, we subsequently explored the delivery of IL-10 by adenoviral gene therapy during EVLP. Ex vivo administered intratracheal adenoviral gene therapy could increase transgene protein levels within the lung. More importantly, it did so with less vector-associated inflammation when compared to in vivo delivery of adenoviral gene therapy. Having explored drug delivery, we sought to develop a large animal injury model on which to test ex vivo therapies. Given that the majority of organ donors are brain dead and therefore exposed to the injurious sequelae resulting from brain death, we developed a brain-death injury model in pig. Use of EVLP as a platform for repair necessitates an accurate recognition of both lung injury and lung improvement during EVLP. Thus, we utilized this injury model to explore the profile of physiological parameters when an injured lung is perfused during EVLP. Because of the alteration of the PO2 to oxygen content relationship of an acellular perfusate, we found that PaO2 changes are less dramatic than in the in vivo situation. However, as injured lungs begin to become edematous, the mechanical effects on the lung by the increased water content can be measured by corresponding falls in compliance and increases in airway pressure. Overall, use of EVLP demonstrates promise for reducing the organ shortage currently prevalent in clinical lung transplantation. Improved evaluation will instill confidence in transplant clinicians to transplant previously questionable organs. Lungs which prove to be injured during evaluation can potentially be repaired using IL-10 therapy as explored herein or with other therapies using the delivery methods described.