To study the pulmonary responses to toxic insult, the biochemical and physiological effects of a known pulmonary toxicant (monocrotaline) were investigated. Monocrotaline is a pyrrolizidine alkaloid obtained from the seeds of Crotalaria spectabilis. When this alkaloid is administered to rats in their drinking water (20 mg/1) for 3 weeks, the lung is damaged, resulting in pulmonary hypertension, inhibition of serotonin transport by the pulmonary endothelium, and right heart hypertrophy. Preceeding the hypertrophy is a doubling of the mass of the lung and right ventricle. The change in mass of the lung preceeds that of the right ventricle. The increases in both organs is characterized by elevated RNA but not DNA. The lung mass increase is not accompanied by changes in collagenous proteins but is accompanied by an 86% increase in total lipids. The right ventricle however, responds to monocrotaline with a 400% increase in collagen protein and no change in lipid content, thereby indicating the lung and right ventricle respond differently to monocrotaline. Time course experiments established that the earliest observable event in monocrotaline induced lung damage is pulmonary edema which develops by day 5 and is resolved by day 10. Monocrotaline metabolites generated by an isolated liver and perfused through an isolated lung do not cause pulmonary edema even at concentrations of monocrotaline metabolites near 1 mM. These metabolites do however, alter the pulmonary endothelial transport of serotonin while other endothelial functions such as norepinephrine transport, angiotensin convertining enzyme and 5'-nucleotidase activities are unchanged. The effect of monocrotaline metabolites on pulmonary endothelial cell transport of serotonin is attenuated when the isolated livers are perfused under conditions which inhibit the formation of metabolites. Therefore, one of the pulmonary effects of monocrotaline that takes weeks to develop in vivo, inhibition of pulmonary endothelial transport of serotonin, can be observed under in vitro conditions. These results also directly demonstrate that the pulmonary damage caused by monocrotaline is a result of hepatic metabolism of monocrotaline to a pneumotoxic form.

No description available.

published_or_final_version / Medicine / Master / Master of Medical Sciences

No description available.

No description available.

published_or_final_version / Pathology / Master / Master of Philosophy

Objective: To investigate the adverse effect of welding exposure on pulmonary function test and respiratory symptoms in welders. Design: Cross-sectional study Setting: Guangzhou, China Subjects: 350 male welders in an automobile assembly factory and 350 controls in MTR corporation who had no exposure to welding fumes and toxic gases. Methods: The data was collected from Guangzhou No.12 People’s Hospital. This inclusion and exclusion criteria for subjects and controls were set. The relationship between pulmonary function, respiratory symptoms and welding exposure was investigated by comparing the prevalence of abnormal pulmonary function and respiratory symptoms among welders and non-welders. Chi-square was used for comparison of categorical variables. Logistic regression was performed to estimate odds ratios after adjustment for age, working duration and smoking habits. Results: After accounting for age, working years and smoking habit, the adjusted OR (95% C.I.) of pulmonary function among welders and non-welders was 1.425 (0.916, 2.215), suggesting that welders was associated with a 1.43 times as high the odds of being tested abnormal pulmonary function as non-welders. However, there was no significant (P=0.116) difference in odds between welders and non-welders. The differences of respiratory symptoms in odds between welders and non-welders was not significant (P>0.268). But when restricted to smokers, significant difference (p<0.05) in abnormal pulmonary function was found between welders (17.5%) and non-welders (10.6%). Of the respiratory symptoms, only prevalence of cough was found to be statistically higher (p<0.05) among welders (16.1%) who smoked than non-welders (8.0%) who smoked. Conclusion: It is not evident from my study thatwelders who worked in a well-ventilation working environment and well protected by wearing personal protective equipment are subjected to increased prevalence of abnormal pulmonary function and respiratory symptoms. Studies with larger samples and longer period of observation are warranted. Smoking was observed to be the most important factor contributing to the presence of abnormal pulmonary function and respiratory symptoms. Smoking cessation would be needed to carry out in welders. / published_or_final_version / Public Health / Master / Master of Public Health

No description available.

Purpose: Exercise testing modalities to assess the effects of a given intervention should prove to be reliable and reproducible. This study reports on test-retest reproducibility of the 3-min shuttle walking and step testing exercise protocols to assess exertional dyspnea and exercise physiology in COPD patients. / Methods: Stable COPD patients (N=43; 65 +/- 6.5 years; FEV1 = 49 +/- 16% pred.) equipped with a portable Jaeger Oxycon MobileRTM metabolic system repeated the walking or stepping tests on two occasions separated by 7 to 14 days. At each visit, participants performed, in a randomized order, four externally paced 3-min bouts of shuttle walking at speeds of 1.5, 2.5, 4.0 and 6.0 km&middot;h-1 or of stepping at a constant rate of 18, 22, 26 and 32 steps&middot;min-1, respectively. Each exercise bout was separated by a 10-min rest period. Ventilation, heart rate, gas exchange parameters and Borg dyspnea score were obtained for each bout during the last 30-seconds of exercise. / Results: The majority of patients completed stepping or walking at the slowest cadence but only 33% completed walking at 6.0 km&middot;h -1 and 40% completed stepping at 32 steps&middot;min-1. Test-retest Pearson correlation coefficients for ventilation, heart rate, gas exchange parameters and dyspnea scores over the four exercise bouts, all exceeded 0.80 with the highest coefficient found for ventilation (r&ge;.95). Intra-class correlation coefficients were similar to Pearson. Bland & Altman representation showed that a similar proportion of dyspnea data points (92 vs. 96%) lied within 2 SD of the mean difference between test-retest values for dyspnea Borg scores during walking and stepping. / Conclusion: Results show very good reproducibility for both 3-min shuttle walking and stepping exercise protocols in patients with COPD. / This study was supported by an unrestricted grant from Boehringer-Ingelheim/Pfizer.

Rationale. There is a need for the development of a field test to evaluate exertional dyspnea in the primary care setting. This study examined the applicability of a 3-minute constant rate step test in patients with COPD. / Methods. This test involved 4 stepping rates (18, 22, 26, 32 steps.min-1) equivalent to approximately 4.5, 5.3, 6.0, and 7.2 MET with the ultimate goal that in its final development, the assessment will be made a single stepping rate based on disease severity. Stable COPD patients (N = 43; 65 +/- 6.5 years; FEV1 = 49 +/- 16% pred.; SpO2 (%) rest: 95 +/- 2) were equipped with a portable Jaeger Oxycon MobileRTM metabolic system and followed an audio signal for stepping up and down a single 20 cm step for 3 minutes. Borg dyspnea scores were obtained at the end each stepping bout. A 10-min rest was given between each stepping bout. / Results. Of the 43 patients, 80% completed stages 1 and 2, 74 and 37% stages 3 and 4 while no patient of MRC class 4 or 5 (N = 8) completed stage 1. Breathing frequency (breaths.min-1) spanned from 26.5 +/- 4.1 to 39.0 +/- 6.4 but VT (L) remained unchanged (1.4 +/- 0.3 vs. 1.5 +/- 0.4) from stage 1 to 4 while Borg scores were 3 +/- 1, 4 +/- 1, 5 +/- 2, 6 +/- 3 respectively and SpO2 (%) were 92 +/- 5, 91 +/- 4, 91 +/- 4 and 90 +/- 4. / Conclusions. Preliminary findings indicate that a 3-minute constant rate step test may present a feasible alternative to laboratory testing to assess exertional dyspnea in moderately severe COPD. In this population, a stepping rate of 26 steps.min-1 could be sustained by the majority of patients while producing a level of dyspnea potentially amenable to therapy. / This study was supported by an unrestricted grant from Boehringer-Ingelheim/Pfizer.