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Biomedical subjects

A W Musk

Publications and source records attributed to A W Musk.

At least 91 records · Page 5Linked to original sources
PubMed1993

Radiographic abnormalities and mortality in subjects with exposure to crocidolite.

Plain chest radiographs from a one in six random sample of the workforce of the asbestos industry at Wittenoom, Western Australia between 1943 and 1966 have been classified for degree of profusion and pleural thickening by two independent observers according to the 1980 UICC-ILO Classification of Radiographs for the pneumoconioses to clarify the effect of degree of radiological abnormality on survival. A total of 1106 subjects were selected. Each subject's age, cumulative exposure to crocidolite, and time since first exposure were determined from employment records, the results of a survey of airborne concentrations of fibres > 5 mu in length conducted in 1966, and an exposure rating by an industrial hygienist and an ex-manager of the mine and mill at Wittenoom. By the end of 1986 193 subjects had died. Conditional logistic regression was used to model the relative risk of death in five separate case-control analyses in which the outcomes were deaths from: (1) all causes, (2) malignant mesothelioma, (3) lung cancer, (4) asbestosis, and (5) other causes excluding cancer and asbestosis. Up to 20 controls per case were randomly chosen from all men of the same age who were not known to have died before the date of death of the index case. After adjustment for exposure and time since first exposure, there were significant and independent effects of radiographic profusion and pleural thickening on all cause mortality. The effect of profusion was largely a result of the effect on mortality from malignant mesothelioma and asbestosis but not lung cancer. The effect of pleural thickening was greatest on mortality from other causes, mainly ischaemic heart disease. This study has shown that degree of radiographic abnormality has an independent effect on mortality from malignant mesothelioma, asbestosis, and all causes even after allowing for the effects of age, degree of exposure, and time since first exposure.

Asbestos, Crocidolite↗
PubMed1993

Variability of the plateau response to methacholine in subjects without respiratory symptoms.

BACKGROUND: Interpretation of measurements of limited maximal airway narrowing, or plateau response, requires knowledge of its variability within subjects and between methods. METHODS: The repeatability of the plateau response to inhaled methacholine with a dosimeter (D) method (maximal dose 210 mumol) and a tidal breathing (T) method (730 mumol), and the agreement of the two methods, were measured in 16 subjects with mild or no asthma. Two tests by each method (D1,D2,T1,T2) were performed in random order over four consecutive days, with a third dosimeter (D3) test one week later. The dose producing a decrease in forced expiratory volume in one second (FEV1) of 10% (PD10) and the plateau were calculated from each dose-response curve. RESULTS: A plateau was reached in all five tests in 12 subjects and in all tests except D3 in 14 subjects. PD10 was inversely related to the plateau (r = -0.95 for D, r = -0.77 for T). The 95% ranges for differences between two determinations of the plateau in a subject were +/- 11.9% (change in FEV1), +/- 19.2%, and +/- 20.3%, estimated from D1-2 and 1-3, and T1-2 tests, respectively. From the same tests the 95% ranges for the difference of a single determination from an individual's true mean value were +/- 8.3%, +/- 13.6%, and +/- 14.3%. The limits of agreement between methods indicated that 95% of the measurements of the plateau by tidal breathing ranged from 15.2% below to 13.3% above those obtained by dosimeter. There was no significant bias between methods. Tachyphylaxis over 24 hours occurred with PD10 but not with the plateau response. CONCLUSIONS: The plateau response is a subject characteristic which is independent of the method of inhalation challenge testing. Repeatability of the plateau is low in this group of subjects with low airway responsiveness.

Adult↗
PubMed1992

Nebuhaler versus wet aerosol for domiciliary bronchodilator therapy. A multi-centre clinical comparison.

OBJECTIVE: To compare the clinical effectiveness and patient acceptance of a large spacer device (Nebuhaler) for delivery of metered dose aerosol (MDI) terbutaline with nebulised wet aerosol terbutaline. DESIGN: Randomised open crossover study over two sequential four week treatment periods, following a two week run-in. SETTING: Multi-centre including five adult thoracic units and three paediatric centres throughout Australia. PATIENTS: Thirty-eight adults and 23 children with clinical asthma and reversible airflow obstruction (increase in forced expiratory volume in one second [FEV1] of greater than or equal to 15% in response to inhaled bronchodilator) entered the study proper. Six adults and one child withdrew. INTERVENTIONS: Terbutaline was administered four times daily via Nebuhaler/MDI or nebuliser. Clinical assessment with spirometry and peak flow readings was made after run-in and at the end of each treatment period. Patients recorded on diary cards daily peak expiratory flow rates and symptom scores and comparisons of these results for each treatment period were made. At the completion of the study patients answered a treatment preference questionnaire. RESULTS: No differences were found between the two treatment periods in diary card peak flow recordings and symptom score data, and in clinical assessment of spirometry and peak expiratory flow rates. There were also no differences between spirometry and peak flow values recorded at the clinic at randomisation and at the end of each treatment period, suggesting stable basal airflow obstruction over the period of the study. Thirty-two per cent of adults and 52% of children preferred the Nebuhaler/MDI combination, mainly because of convenience of use. Treatment preference was not related to any measured index of lung function. CONCLUSIONS: MDI terbutaline delivered via Nebuhaler provides clinical benefit similar to that of wet aerosol terbutaline in the long-term domiciliary management of patients with stable airflow obstruction.

Adult↗
PubMed1992

Respiratory disease in non-smoking Western Australian goldminers.

Respiratory symptoms, spirometry, and transfer factor were measured in 208 non-smoking Western Australian underground goldminers (mean age 32) to identify the presence of respiratory abnormalities resulting from underground work. These subjects were part of a larger group of 771 subjects attending for statutory periodic chest x ray examinations in the industry. They had worked underground for a median of three years. The prevalence odds ratios of bronchitis, dyspnoea, wheeze, and asthma all tended to be related to duration of underground employment, even after adjusting for age, those for wheeze and asthma reaching statistical significance. After adjusting for age and height the duration of employment also had a significant effect on TL/VA but not on FEV1, FVC, or TL. These changes are consistent with the presence of airway narrowing and non-specific lung fibrosis or emphysema in non-smoking underground goldminers.

Adolescent↗
PubMed1992

Immune response to flour and dust mites in a United Kingdom bakery.

In a study of 279 United Kingdom bakery workers a high prevalence of immunological response to storage mites was found. To determine whether this was the consequence of exposure to storage mites in bakery work, a population of salt packing workers was examined as a comparison group not at occupational risk of exposure to storage mites. Forty two per cent of both groups were atopic (had a positive skin prick response greater than negative controls to D pteronyssinus, grass pollen, or cat fur by 2 mm or more) and 33% had an immediate skin prick test response to at least one of four storage mites (L destructor, G domesticus, T putrescentiae, A Siro). A higher percentage of the salt packing workers than the bakery workers had a positive radioallergosorbent test (RAST) (greater than or equal to 0.35 PRU) to D pteronyssinus and to the four storage mites. Logistic regression analysis identified atopy as the most significant variable for a positive skin test and RAST response to storage mites in both groups of workers. RAST inhibition was used to analyse extracted area and personal air samples. Analysis of static area samples for aeroallergen showed immunological identity with flour but L destructor was found in only one of seven exposed filters. The concentration of airborne flour was related to exposure rank of perceived dustiness and gravimetric measurement of total dust. Nineteen out of 32 filters from workers in jobs with higher dust exposure (rank >/=6) had a level of > 10 microgram/m(3) flour whereas this concentrations was exceeded in only one of 23 filters from workers in low dust exposure (< rank 6). It is concluded that storage mites are not of special significance in allergic responses in bakery workers. The development of immunological (and airway) responsiveness to inhaled flour dust is increased in those exposed to higher concentrations of airborne allergen, which appears to be predominantly flour and not storage mites.

Air Pollutants, Occupational↗
PubMed1991

Establishment and characterization of five human malignant mesothelioma cell lines derived from pleural effusions.

Malignant mesothelioma (MM) is an aggressive tumour of the serosal cavities which is associated with exposure to asbestos. Studies of this tumour have been limited by a paucity of well-characterized human MM cell lines. In this study, 5 human MM cell lines were established from pleural effusions of patients with this malignancy. All 5 patients were males with known crocidolite asbestos exposure, who had received no treatment for their disease and in whom the diagnosis was confirmed by cytology, histology and electron microscopy (EM). These lines have been in culture from 11 to 25 months, and all of them for more than 18 passages. The appearance of the cells in culture was extremely varied; in 3 of the lines they were spindle-shaped with few vacuoles (JU77, LO68 and ONE58); in 1 line they had a thick, stellate shape with vacuoles (NO36) and in 1 they were very pleomorphic in both shape and size with irregular membranes and numerous vacuoles [DeH128 (M)]. Upon reaching confluence, cells in 3 of the 5 lines assumed the cobblestone-like pattern characteristic of epithelial-type cells, whereas in the other 2 (LO68 and ONE58) they remained spindle-shaped. All 5 lines demonstrated a loss of contact inhibition (i.e., piling) at confluence. Minimum doubling times varied significantly from 18 hr (JU77) to more than 30 hr [DeH128 (M)]. Cytological examination showed characteristic mesothelial/mesothelioma morphology, and epithelial membrane antigen (EMA) and cytokeratin were demonstrated in cells from all 5 lines. These cells lacked CEA and epithelial mucin. The presence of cell junctions, glycogen and numerous long, thin, branching microvilli was readily demonstrable by EM. All lines had abnormal karyotypes, with the modal chromosome number varying from 40 to 80. Variable chromosome numbers, numerous structural rearrangements and unrecognizable marker chromosomes were readily observed; however, the only consistent change seen was del 6q21 in 4 of the 5 lines. The establishment of these 5 cultured human MM cell lines now provides an opportunity for comparative study of several aspects of the biology of MM in vitro as well as screening new treatment modalities.

Adult↗
PubMed1991

Relative risks of bronchial hyper-responsiveness associated with skin-prick test responses to common antigens in young adults.

We studied 143 young subjects by skin-prick testing to common allergens and by the measurement of non-specific bronchial responsiveness (NSBR). A logistic regression model showed a prevalence odds ratio (POR) for bronchial hyper-responsiveness (PD20 less than 10 mumol methacholine) in house dust positive subjects of 4.10 (95% CI 1.77-9.51, P less than 0.001), and in mould positive subjects 5.72 (95% CI 2.06-15.9, P less than 0.001): the PORs for epithelia (2.05, P = 0.12) and grasses (1.78, P = 0.19) were not significant. If bronchial reactivity was assessed as measurable (PD20 less than 102 mumol methacholine) or not, the POR for house-dust-positive subjects was 4.83 (95% CI 2.23-10.5, P less than 0.001), for moulds was 10.5 (95% CI 2.33-47.5, P less than 0.001), for epithelia was 4.79 (95% CI 1.91-12.0, P less than 0.001), and for grasses was 2.21 (95% CI 1.11-4.4, P = 0.022). The results show the risk of bronchial hyper-responsiveness is greater in subjects sensitive to house dust and mould than in those reactive to grasses, and suggests that the presence or absence of increased NSBR in atopic individuals may depend on the antigens to which they become sensitized.

Adolescent↗
PubMed1991

Miliary spread of malignant pleural mesothelioma without a clinically identifiable pleural tumour.

A 44-year-old man with past minor exposure to blue asbestos presented with supraclavicular lymphadenopathy and miliary shadowing on his chest radiograph. Cytology and electronmicroscopy on material obtained by fine needle aspiration from his cervical lymph node revealed malignant mesothelioma. Malignant mesothelioma cells were also present in bronchoalveolar lavage fluid and on transbronchial lung biopsy. At autopsy the right pleural cavity was studded with small tumour nodules. This case demonstrates that malignant mesothelioma may present as metastatic disease and without evidence on conventional investigations of a primary pleural tumour.

Adult↗
PubMed1991

Risk factors for death in patients admitted to hospital with asthma: a follow-up study.

Hospital records of patients with asthma admitted to teaching hospitals in Perth, Western Australia between 1976 and 1980 were examined retrospectively to identify characteristics of the illness which were associated with subsequent death. From 5722 admissions there were 195 deaths to December 1982, 186 of whom had records available (cases); 452 of the surviving subjects were used for comparison (controls). There was no difference in age of onset of asthma or cigarette smoking habits between the two groups, but ischaemic heart disease as an associated condition was significantly more frequent in cases. On admission to hospital an arterial PCO2 less than 45 mmHg was more frequent in those who died, but there were no differences in arterial PO2, lowest pH, highest or lowest FEV1 and FVC. Cases more frequently used home nebulisers and were more frequently prescribed corticosteroids, antibiotics and sedatives or tranquilizers prior to admission, corticosteroids and sedatives or tranquilisers during admission and sedatives or tranquilisers on discharge. These results suggest that cases had more severe asthma in that they were more often treated with home nebulisers, corticosteroids and antibiotics, but with the exception of PaCO2 the commonly used measurements of severity of asthma did not identify those at risk of death. The prescription of sedatives or tranquillisers appears to be associated with an increased risk of death in subjects with asthma.

Adolescent↗
PubMed1991

Smoking, exposure to crocidolite, and the incidence of lung cancer and asbestosis.

In 1979 all former workers from the Wittenoom asbestos industry who could be traced to an address were sent a questionnaire to determine smoking history. Occupational exposure to crocidolite was known from employment records. Of 2928 questionnaires sent, satisfactory replies were received from 2400 men and 149 women. Eighty per cent of these had smoked at some time and 50% were still smoking. Since that time 40 cases of lung cancer and 66 cases of compensatable asbestosis have occurred in this cohort. The incidence of both lung cancer and asbestosis was greatest in those subjects with the highest levels of exposure to crocidolite and in ex-smokers. Statistical modelling of the joint effects of these exposures on the incidence of each disease indicated that crocidolite exposure multiplied the rates of lung cancer due to smoking and that smoking has no measurable effect on the rates of asbestosis. There was also some evidence that the incidence rate of lung cancer is falling with time.

Asbestos↗
PubMed1990

Computer quantitation of gallium 67 lung uptake in crocidolite (blue asbestos) workers of Western Australia.

Pulmonary inflammation has been evaluated in 43 crocidolite-exposed asbestos (ASB) workers and 12 control subjects, using a quantitative index of gallium uptake (GI). The GI was compared with chest roentgenographs (CXRs) graded by the ILO classification. The ASB workers included 15 with asbestosis (CXR greater than or equal to 1/0), 19 with a normal CXR (CXR 0/0), and 9 with equivocal CXR changes (CXR 0/1). In individuals with asbestosis the GI was 3.6 +/- 0.3 (mean +/- SEM), P less than 0.01 compared with exposed patients without asbestosis. In exposed patients with equivocal CXR changes (0/1) the GI was 3.1 +/- 0.3, and in exposed patients with a normal CXR (0/0) the GI was 2.4 +/- 0.2. The GI for subjects without lung disease was 1.2 +/- 0.2, P less than 0.01 compared with exposed patients without asbestosis. The scans were scored independently by two observers, and the correlation coefficient of the two sets of GI was 0.95. These data demonstrate that subjects with crocidolite-induced asbestosis and exposed patients with equivocal CXR changes or a normal CXR have significantly increased GI.

Asbestos↗
PubMed1990

The effects of nedocromil sodium on the response to grain dust in West Australian grain workers.

Seasonal grain workers in Western Australia who develop respiratory symptoms after exposure to grain dust develop concomitant changes in lung function and bronchial responsiveness to methacholine. The mechanisms underlying these changes are not known. A detailed study was undertaken of seasonal grain workers in Western Australia to evaluate the effect of nedocromil sodium (Fisons, United Kingdom) on these changes to see if they could be prevented by this drug. Forty seven subjects participated. Symptoms and forced expiratory volume in one second (FEV1) were recorded before the study and before, during, and after each working shift, and bronchial responsiveness to methacholine was measured at the beginning and end of the study. Twenty three subjects received nedocromil and 22 received a placebo in a double blind design; there was no difference in baseline characteristics between the two groups. At the end of the study, no differences were found between the nedocromil and placebo groups in the prevalence of symptoms or development of new symptoms during the study. The drug had no effect on changes in methacholine PD20 or FEV1. As in previous studies, new symptoms developing during the season were more common in atopic subjects and were associated with a fall in methacholine PD20. It is concluded that nedocromil has no effect on the development of new symptoms in grain workers. The mechanisms underlying these symptoms require further study.

Adolescent↗
PubMed1990

Comparison of chest radiograph reading methods for assessing progress of pneumoconiosis over 10 years in Wittenoom crocidolite workers.

Thirty three pairs of chest radiographs taken up to 10 years apart were obtained for 33 subjects suffering from asbestosis who had applied for compensation to the Pneumoconiosis Medical Board of Western Australia. Multiple films from the period before the first radiograph in each pair, from the intervening period between the two, and from the period subsequent to the second radiograph were also available and all films were read by two independent readers according to the 1980 ILO classification of pneumoconiosis. Films were read twice as side by side pairs ten years apart, twice as two separate randomly ordered films ten years apart, and once as part of the full series of all available chest radiographs on each subject to assess which method provided the best consistency (between reader variation) and repeatability (within reader variation). Judging by consistency, the full series method performed as well as either of the other methods when assessing radiographic changes and significantly better when assessing the level of profusion of small opacities. There was little to choose between the other two methods either judging by consistency or repeatability, which could not be estimated for the full series method. Use of all available films for a subject is recommended for assessing single films, as in a prevalence study, as well as for documenting change in a longitudinal study.

Asbestos↗
PubMed1990

Exposure to grain dust and changes in lung function.

Respiratory symptoms and lung function were assessed in 41 seasonal grain handlers and related to duration of employment and level of exposure to grain dust. Ten public works department employees, not exposed to grain dust, were examined during the same period. Respiratory symptoms, forced expired volume in one second (FEV1), and bronchial responsiveness (dose of methacholine provoking a 20% fall in FEV1-PD20) were assessed before starting work and at weekly intervals during a period of employment lasting up to four weeks. Two atopic grainhandlers with pronounced bronchial hyperresponsiveness (PD20 less than 1 mumol) and a history of asthma withdrew from the study within two weeks because they developed severe asthma. Respiratory symptoms were more frequent and more often attributed to work in the grainhandlers than in the non-exposed subjects. In the grainhandlers the FEV1 decreased by a mean (95% confidence intervals) of 321 ml (198-444) (p less than 0.05) and the mean (95% confidence interval) PD20 decreased from 20.6 mumol (10.3-41.2) to 6.0 mumol (2.8-12.5) (p less than 0.05) after one week of work. Over the next three weeks the mean FEV1 returned towards the prestudy values. The mean PD20, however, remained significantly lower than the initial value. The mean FEV1 and PD20 did not change significantly in the non-exposed subjects. The frequency of symptoms and decreases in FEV1 were greater in grainhandlers when working in jobs where total exposure to dust was greater than 20 mg/m3 than when working in jobs where it was less than 10 mg/m3. The results indicate that occupational exposure to grain dust results in respiratory symptoms and changes in lung function, including increased airway responsiveness, within the first week of exposure to grain dust at work. These changes appear to be determined by the degree of dust exposure and suggest a direct effect of grain dust on the lung in these subjects.

Agricultural Workers' Diseases↗