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Biomedical subjects

A W Musk

Publications and source records attributed to A W Musk.

At least 19 recordsLinked to original sources
PubMed2006

AluyMICB dimorphism within the class I region of the major histocompatibility complex is associated with asthma and airflow obstruction in the Busselton population.

AIM: To examine the association between the Alu dimorphism within the first intron of the MICB gene and asthma and airflow obstruction. Background The highly polymorphic non-classical MHC class I polypeptide-related (MIC) genes, MICA and MICB, encode stress inducible glycoproteins, which are expressed on a variety of epithelial cells, including those of the lungs. METHODS: AluyMICB genotyping was performed on 1109 subjects from the Busselton Health Study. From a standard questionnaire, 359 individuals indicated that they had been diagnosed by a doctor with asthma. Lung function was assessed by the forced expired volume in 1 second (FEV1) and expressed as a percent of the predicted value. Airflow obstruction was defined as FEV1<80% predicted. RESULTS: In men, a dominant relationship was found between the AluyMICB DD genotype and asthma (P=0.006; chi2(2)=7.65). Furthermore, multivariate analysis adjusted for age, height, weight and body mass index (BMI) showed a relationship between DD genotype and asthma in men in a dominant model (odds ratio (OR)=1.97; 95% confidence interval (CI)=1.11-3.51; P=0.021). In women, an association was found between the AluyMICB II genotype and FEV1 percent predicted as a continuous variable (P=0.001). When adjusted for age and BMI, it showed a significant relationship between AluyMICB and airflow obstruction in a dominant model (OR=14.11%, 95% CI 3.29-60.57, P<0.001). However, no association was found between the AluyMICB II genotypes and airflow obstruction in men. CONCLUSION: These findings suggest the possible involvement of a MHC class I gene in abnormal airway structure in women and airway function in men.

Adult↗
PubMed2006

The risk of lung cancer with increasing time since ceasing exposure to asbestos and quitting smoking.

OBJECTIVES: To examine if the risk of lung cancer declines with increasing time since ceasing exposure to asbestos and quitting smoking, and to determine the relative asbestos effect between non-smokers and current smokers. METHODS: A cohort study of 2935 former workers of the crocidolite mine and mill at Wittenoom, who responded to a questionnaire on smoking first issued in 1979 and on whom quantitative estimates of asbestos exposure are known. Conditional logistic regression was used to relate asbestos exposure, smoking category, and risk of lung cancer. RESULTS: Eighteen per cent of the cohort reported never smoking; 66% of cases and 50% of non-cases were current smokers. Past smokers who ceased smoking within six years of the survey (OR = 22.1, 95% CI 5.6 to 87.0), those who ceased smoking 20 or more years before the survey (OR = 1.9, 95% CI 0.50 to 7.2), and current smokers (<20 cigarettes per day (OR = 6.8, 95% CI 2.0 to 22.7) or >20 cigarettes per day (OR = 13.2, 95% CI 4.1 to 42.5)) had higher risks of lung cancer compared to never smokers after adjusting for asbestos exposure and age. The asbestos effect between non-smokers and current smokers was 1.23 (95% CI 0.35 to 4.32). CONCLUSION: Persons exposed to asbestos and tobacco but who subsequently quit, remain at an increased risk for lung cancer up to 20 years after smoking cessation, compared to never smokers. Although the relative risk of lung cancer appears higher in never and ex-smokers than in current smokers, those who both smoke and have been exposed to asbestos have the highest risk; this study emphasises the importance of smoking prevention and smoking cessation programmes within this high risk cohort.

Asbestos, Crocidolite↗
PubMed2005

The additional risk of malignant mesothelioma in former workers and residents of Wittenoom with benign pleural disease or asbestosis.

AIMS: To examine the hypothesis that people with benign pleural disease or asbestosis have an increased risk of malignant mesothelioma beyond that attributable to their degree of asbestos exposure. METHODS: Former workers and residents of the crocidolite mining and milling town of Wittenoom are participating in a cancer prevention programme (n = 1988). The first plain chest radiograph taken at the time of recruitment into the cancer prevention programme was read for evidence of benign pleural disease and asbestosis, using the UICC classification. Crocidolite exposure of former workers was derived from employment records and records of dust measurements performed during the operation of the asbestos mine and mill between 1943 and 1966. Based on fibre counts, exposure for former residents was determined using duration of residence and period of residence (before and after a new mill was commissioned in 1957) and interpolation from periodic hygienic measures undertaken from personal monitors between 1966 and 1992. Cox proportional hazards modelling was used to relate benign pleural disease, asbestosis, asbestos exposure, and mesothelioma. RESULTS: Between 1990 and 2002, there were 76 cases of mesothelioma (56 of the pleura and 20 of the peritoneum). Cases had more radiographic evidence of (all) benign pleural disease, pleural thickening, blunt/obliterated costophrenic angle, and asbestosis than non-cases. Adjusting for time since first exposure (log years), cumulative exposure (log f/ml-years), and age at the start of the programme, pleural thickening (OR = 3.1, 95% CI 1.2 to 7.6) and asbestosis (OR = 3.3, 95% CI 1.3 to 8.6) were associated with an increased risk of peritoneal mesothelioma. There was no increased risk for pleural mesothelioma. CONCLUSION: The presence of benign pleural disease, in particular pleural thickening, and asbestosis appears to increase the risk of mesothelioma of the peritoneum, but not of the pleura beyond that attributable to indices of asbestos exposure in this cohort of subjects exposed to crocidolite.

Aged↗
PubMed2005

The effect of asbestosis on lung cancer risk beyond the dose related effect of asbestos alone.

AIMS: To determine if the presence of asbestosis is a prerequisite for lung cancer in subjects with known exposure to blue asbestos (crocidolite). METHODS: Former workers and residents of Wittenoom with known amounts of asbestos exposure (duration, intensity, and time since first exposure), current chest x ray and smoking information, participating in a cancer prevention programme (n = 1988) were studied. The first plain chest radiograph taken at the time of recruitment into the cancer prevention programme was examined for radiographic evidence of asbestosis according to the UICC (ILO) classification. Cox proportional hazards modelling was used to relate asbestosis, asbestos exposure, and lung cancer. RESULTS: Between 1990 and 2002 there were 58 cases of lung cancer. Thirty six per cent of cases had radiographic evidence of asbestosis compared to 12% of study participants. Smoking status was the strongest predictor of lung cancer, with current smokers (OR = 26.5, 95% CI 3.5 to 198) having the greatest risk. Radiographic asbestosis (OR = 1.94, 95% CI 1.09 to 3.46) and asbestos exposure (OR = 1.21 per f/ml-year, 95% CI 1.02 to 1.42) were significantly associated with an increased risk of lung cancer. There was an increased risk of lung cancer with increasing exposure in those without asbestosis. CONCLUSION: In this cohort of former workers and residents of Wittenoom, asbestosis is not a mandatory precursor for asbestos related lung cancer. These findings support the hypothesis that it is the asbestos fibres per se that cause lung cancer, which can develop with or without the presence of asbestosis.

Aged↗
PubMed2004

Malignant pleural and peritoneal mesotheliomas in former miners and millers of crocidolite at Wittenoom, Western Australia.

AIMS: To report the number of malignant pleural and peritoneal mesotheliomas that have occurred in former Wittenoom crocidolite workers to the end of 2000, and to compare this with earlier predictions. METHODS: A group of 6493 men and 415 women who had worked at the former Wittenoom crocidolite mine and mill at some time between 1943 and 1966 have been followed up throughout Australia and Italy to the end of 2000. RESULTS: The cumulative number of mesotheliomas up to 2000 was 235 in men (202 pleural, 33 peritoneal) and seven (all pleural) in women. There had been 231 deaths with mesothelioma (9% of known deaths). CONCLUSIONS: The number of deaths in men with mesothelioma between 1987 and 2000 was at the low end of the predictions made earlier based on the number of cases to 1986. If this trend continues, it is predicted that about another 110 deaths with mesothelioma will occur in men by 2020.

Adult↗
PubMed2004

Effects of asbestos and smoking on the levels and rates of change of lung function in a crocidolite exposed cohort in Western Australia.

BACKGROUND: Increased rates of death from asbestos related diseases have been reported in former workers and residents exposed to crocidolite (blue asbestos) at Wittenoom, Western Australia. Exposure to asbestos is associated with reduced static lung volumes, gas transfer and lung compliance, and a restrictive ventilatory abnormality. METHODS: The effects of crocidolite exposure and smoking history on levels and rates of change of lung function were evaluated using a linear mixed model. Lung function was measured as forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV1/FVC. RESULTS: Cumulative doses of asbestos and the presence of radiographic asbestosis were associated with lower levels of FEV1 and FVC and a steeper decline during the period of observation. Subjects exposed to asbestos at a younger age had lower levels of FEV1 and FVC. Current smokers had lower levels and a steeper decline in lung function than never smokers. No significant interactions between crocidolite exposure and smoking on the levels or rates of change of lung function were found. CONCLUSIONS: The deleterious effects of crocidolite exposure on lung function persist in this population, despite asbestos exposure having ceased more than 30 years ago. No significant interactions were found in this population between asbestos and smoking at the first visit or longitudinally.

Asbestos, Crocidolite↗
PubMed2003

Comparison of an Australian food-frequency questionnaire with diet records: implications for nutrition surveillance.

OBJECTIVES: To compare a widely used Australian food-frequency questionnaire (FFQ) with diet records and consider the results in relation to its use in nutrition surveillance. DESIGN: Inter-method reliability study. SETTING: A randomised trial in subjects with past asbestos exposure. SUBJECTS: Seventy-two adults living in Western Australia. METHODS: A semi-quantitative FFQ developed by the Commonwealth Scientific Industrial Research Organisation in South Australia was administered after the completion of four 7-day diet records (DRs). RESULTS: Mean agreement between methods was not significantly different from 100% for many nutrients, but the limits of agreement indicated that, at the individual level, the FFQ over- or underestimated the DR by at least 50%. Mean agreement between methods decreased significantly with increasing intakes for the majority of nutrients. Pearson's correlation coefficients were less informative indicators of agreement compared with the limits of agreement. CONCLUSIONS: These results indicate poor agreement between the FFQ and DR when estimating absolute intakes. Therefore, comparing intakes collected using this FFQ with specific cut-off points such as Recommended Dietary Intakes for nutrition surveillance may lead to seriously flawed conclusions about population intakes.

Australia↗
PubMed2003

Radiographic (ILO) readings predict arterial oxygen desaturation during exercise in subjects with asbestosis.

BACKGROUND: Exercise impairment is common in subjects with asbestosis. Arterial oxygen desaturation during exercise is an important contributor to exercise limitation. The International Labour Office (ILO) classification of plain chest radiographs correlates with resting pulmonary function, but its value in predicting abnormal ventilatory responses to exercise, including desaturation, has not been explored. AIMS: To determine in subjects with asbestosis (1) if radiographic profusion scores and the extent of small irregular shadows on plain chest radiographs correlate with resting lung function and abnormal ventilatory responses to exercise; and (2) if radiographic scores add value to resting lung function tests in predicting abnormal ventilatory responses to exercise. METHODS: Thirty eight male subjects with asbestosis were included. Plain chest radiographs were read according to the ILO classification independently by three observers. All subjects underwent assessment of lung function and an incremental exercise test. RESULTS: Profusion scores and number of affected zones correlated significantly with the percentage predicted values of single breath diffusing capacity (DLCO), forced vital capacity (FVC), and total lung capacity (TLC). Arterial oxygen desaturation occurred in 29% of the subjects. The severity of desaturation correlated significantly with profusion and the number of affected zones. The combined use of number of affected zones, FEV(1)/FVC ratio and DLCO predicted desaturation during exercise with an explained variance of 41%. VO(2)max was significantly related only to DLCO but was not predicted by the ILO score. CONCLUSION: Arterial oxygen desaturation correlated with the profusion and extent of parenchymal abnormality on chest radiographs. The addition of morphological indices to physiological measurements is valuable for predicting oxygen desaturation during exercise but not for VO(2)max. Refinement of the radiographic scoring system and the addition of more sophisticated imaging techniques may further improve the predictive power.

Aged↗
PubMed2002

A multicentre phase II study of cisplatin and gemcitabine for malignant mesothelioma.

Our previous phase II study of cisplatin and gemcitabine in malignant mesothelioma showed a 47.6% (95% CI 26.2-69.0%) response rate with symptom improvement in responding patients. Here we confirm these findings in a multicentre setting, and assess the effect of this treatment on quality of life and pulmonary function. Fifty-three patients with pleural malignant mesothelioma received cisplatin 100 mg m(-2) i.v. day 1 and gemcitabine 1000 mg m(-2) i.v. days 1, 8, and 15 of a 28 day cycle for a maximum of six cycles. Quality of life and pulmonary function were assessed at each cycle. The best response achieved in 52 assessable patients was: partial response, 17 (33%, 95% CI 20-46%); stable disease, 31 (60%); and progressive disease, four (8%). The median time to disease progression was 6.4 months, median survival from start of treatment 11.2 months, and median survival from diagnosis 17.3 months. Vital capacity and global quality of life remained stable in all patients and improved significantly in responding patients. Major toxicities were haematological, limiting the mean relative dose intensity of gemcitabine to 75%. This schedule of cisplatin and gemcitabine is active in malignant mesothelioma in a multicentre setting. Investigation of alternative scheduling is needed to decrease haematological toxicity and increase the relative dose intensity of gemcitabine whilst maintaining response rate and quality of life.

Aged↗
PubMed2002

Gene frequencies of human platelet antigens 1-5 in indigenous Australians in Western Australia.

The frequencies of human platelet antigen (HPA) systems vary between different racial groups; however, HPA frequency data for some racial groups are still incomplete. We report the distribution of HPA 1-5 systems in Australian Aborigines from a remote community in the north-west of Australia and compare our findings with HPA observed in a Western Australian blood donor population. Using a polymerase chain reaction (PCR) with sequence-specific primers, 185 indigenous Australians and 1000 Western Australian blood donors were genotyped for each of the HPA 1-5 systems. Comparison of gene frequencies of alleles from HPA-1, -2, -3 and -5 systems showed significant differences between Aboriginal people and Western Australian blood donors (P < 0.001). In particular, the frequency of HPA-3b (0.068) in the Australian Aboriginals, from this study, was one of the lowest reported, whilst the frequency of HPA-5b (0.246) was one of the highest for this allele. Gene frequencies were similar to those reported for central Australian Aborigines but with no other ethnic group. In conclusion, this study confirms significant differences in HPA distributions between indigenous Australians, Australian blood donors and other racial groups. These results indicate a higher potential risk of alloimmunization to HPA-1, -2 and -3 in Australian Aborigines receiving transfusion therapy from a Caucasian blood donor population, thereby having practical implications for transfusion and pregnancy risks in people of Aboriginal origin.

Antigens, Human Platelet↗
PubMed2002

Silicosis compensation in Western Australian gold miners since the introduction of an occupational exposure standard for crystalline silica.

UNLABELLED: Occupational exposure limits for crystalline silica are under review worldwide because of the large numbers of exposed people and, especially, because of the recent International Agency for Research on Cancer classification of silica as a human carcinogen. OBJECTIVES: The aims of this study were to (i) re-examine the incidence of silicosis in Western Australian gold miners and, using estimates of the total population at risk, (ii) estimate the upper confidence limit for the risk of silicosis in Western Australian gold miners since 1974, when the current exposure standard for crystalline silica was implemented. METHODS: Work histories of cases compensated for pneumoconiosis after 1974 were examined. Numbers of workers in the total workforce likely to be exposed to crystalline silica in Western Australia were estimated as the population at risk. RESULTS: There were no cases of compensated silicosis in Western Australian miners whose first dust exposure began during or after 1974. The upper 95% confidence interval for this zero rate was estimated to be 4.8 per 100,000 person-yr. CONCLUSIONS: There have been no compensated cases of silicosis in Western Australia among miners first exposed to crystalline silica after introduction of the current exposure standard. A rate of compensated silicosis higher than five cases per 100,000 person-yr is unlikely.

Adult↗
PubMed2001

p53 autoantibodies in patients with malignant mesothelioma: stability through disease progression.

Malignant mesothelioma (MM) generally occurs as a pleural tumour, related to the inhalation of asbestos fibres. It is highly aggressive and largely unresponsive to treatment. The incidence of MM is particularly high in Western Australia because of the extensive blue asbestos mining operations that occurred in the north of the state until 1966. MM is unusual in that mutations in the tumour suppressor gene p53 are rarely observed, whilst over-expression of p53 protein is common. As the level of antibodies directed against p53 is thought to be of prognostic value in some cancers and as MM is known to be immunogenic, we studied a cohort of Western Australian patients to determine the prevalence of anti-p53 antibodies and their value as diagnostic markers or prognostic indicators. 6/88 (7%) of patients had high titres (>2 SD above the mean of controls) of anti-p53 antibodies. There was no correlation between antibody titre and survival. Although 3/38 (8%) of sera obtained from patients exposed to asbestos but prior to a diagnosis of MM contained antibodies, the same proportion of sera obtained from patients exposed to asbestos but who remained disease free also contained antibodies (2/40; 8%). Sera collected sequentially demonstrated a profound temporal stability in the titre of anti-p53 antibodies in patients with MM throughout the course of their illness. These results show that anti-p53 antibodies are observed only at a low frequency in the sera of MM patients and where they do occur, their elicitation is an early event that may be unrelated to antigen load. The occurrence of anti-p53 antibodies does not serve as either a useful prognostic or diagnostic indicator in MM.

Adult↗
PubMed2001

Increased body mass index is related to apparent circumscribed pleural thickening on plain chest radiographs.

BACKGROUND: Diffuse pleural thickening and pleural plaques are the commonest radiological manifestations of asbestos exposure. Differentiation between subpleural fat and non-calcified pleural plaques is important clinically and medico-legally. This study aims to determine if apparent circumscribed pleural thickening on chest radiographs is related with obesity. METHODS: Surveillance chest x-rays of 693 former asbestos workers were read with the ILO classification. Subjects with costophrenic angle obliteration (n = 57) were analyzed separately. The remaining subjects were subdivided according to their body mass index (BMI): Group 1 < 26 kg/m(2); Group 2 26-30 kg/m(2); Group 3 > 30 kg/m(2). RESULTS: Baseline characteristics, asbestos exposure, and profusion scores were evenly distributed. BMI of > 30 kg/m(2) was associated with a higher prevalence of pleural thickening on CXR (Gp1 = 8.5%; Gp2 = 9.3%; Gp3 = 18.3%). This relationship was strongest in the subgroups with 25-50% of the lateral chest wall involved and pleural thickness of < 10 mm. CONCLUSIONS: Obesity (BMI > 30 kg/m(2)) is related to apparent circumscribed pleural thickening on CXR, especially thin (< 1 cm) shadows covering 25-50% of the lateral chest wall.

Adipose Tissue↗
PubMed2001

Gibbs sampling-based segregation analysis of asthma-associated quantitative traits in a population-based sample of nuclear families.

Asthma is a common, complex human disease. Elevated serum immunoglobulin E (IgE) levels, elevated blood eosinophil counts, and increased airway responsiveness are physiological traits that are characteristic of asthma. Few studies have investigated major gene effects for these traits in a population-based sample. Further, it is not known if any putative major genes may be common to two or more of these traits. We investigated the existence and nature of major genes modulating asthma-associated quantitative traits in an Australian population-based sample of 210 Caucasian nuclear families. The sharing of these major genes was also investigated. Segregation analysis was based upon a Markov Chain Monte Carlo (Gibbs sampling) approach as implemented in the program BUGS v0.6. All models included adjustment for age, height, tobacco smoke exposure, and gender. The segregation of total IgE levels, blood eosinophil counts, and dose-response slope (DRS) of methacholine challenge were all consistent with major loci at which a recessive allele acted to increase or decrease the phenotype. The respective estimated frequencies of the recessive alleles were 68% (total IgE), 10% (blood eosinophil count), and 27% (DRS). Extensive modelling suggested that the major loci controlling total serum IgE levels, blood eosinophil counts, and airway responsiveness represent different genes. These data provide evidence, for the first time, of the existence of at least 3 distinct genetic pathways involving major gene effects on physiological traits closely associated with asthma. These results have implications for gene discovery programs.

Adolescent↗
PubMed2001

Respiratory symptoms and lung function in bauxite miners.

OBJECTIVES: To determine whether cumulative bauxite exposure is associated with respiratory symptoms or changes in lung function in a group of bauxite miners. METHODS: Current employees at three bauxite mines in Australia were invited to participate in a survey comprising: questionnaire on demographic details, respiratory symptoms, and work history; skin prick tests for four common aeroallergens; and spirometry. A task exposure matrix was constructed for bauxite exposure in all tasks in all jobs based on monitoring data. Data were examined for associations between cumulative bauxite exposure, and respiratory symptoms and lung function, by regression analyses. RESULTS: The participation rate was 86%. Self-reported work-related respiratory symptoms were reported by relatively few subjects (1.5%-11.8%). After adjustment for age and smoking no significant differences in the prevalence of respiratory symptoms were identified between subjects, in the quartiles of cumulative bauxite exposure distribution. The forced expiratory volume in I s (FEV1) of the exposed group was found to be significantly lower than that for the unexposed group. After adjustment for age, height, and smoking there were no statistically significant differences between quartiles in FEVI, forced vital capacity (FVC) and FEVl/FVC ratio. CONCLUSIONS: These data provide little evidence of a serious adverse effect on respiratory health associated with exposure to bauxite in an open-cut bauxite mine in present day conditions.

Adult↗
PubMed2001

Association between quantitative traits underlying asthma and the HLA-DRB1 locus in a family-based population sample.

The region of human chromosome 6 containing the MHC has been identified as influencing asthma and atopy (allergy) by several genome-wide searches. The MHC contains many genes with potential effects on innate and specific immunity. As a first step in dissecting MHC influences on asthma and its underlying quantitative phenotypes, we have examined the HLA-DRB1 locus in a population sample consisting of 1004 individuals from 230 families from the rural Australian town of Busselton. The locus was strongly associated with the (log(e)) total serum IgE concentration, accounting for 4.0% of the sigma(2) (variance) in that trait (multi-allelic test, P=0.00001). The locus also influenced specific IgE titres to common allergens (multi-allelic tests, 2.8% sigma(2) for the house dust mite allergen Der p I, P=0.0013; 3.0% of sigma(2) for Der p II, P=0.0007; and 2.1% of sigma(2) for the cat allergen Fel d I, P=0.014). No associations were found to the categorical phenotype of asthma, or to the quantitative traits of peripheral blood eosinophil counts and bronchial hyper-responsiveness. Transmission disequilibrium tests excluded genetic admixture as a cause of false-positive findings. The results indicate that HLA-DRB1 alleles modulate the total serum IgE concentration and IgE responses to allergens, but do not account for the previous observations of linkage of asthma to the MHC.

Adult↗