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Biomedical subjects

A W Musk

Publications and source records attributed to A W Musk.

At least 109 records · Page 6Linked to original sources

Upper-limb and lower-limb exercise training in patients with chronic airflow obstruction.

We designed a randomized controlled study to evaluate the benefit of upper-limb exercise training, alone and in combination with walking training, in patients with severe CAO. In an outpatient department supervised by a physiotherapist, we evaluated 28 patients with severe stable CAO (FEV1, 32 percent of predicted). Patients were randomly allocated to either a control (eight), upper-limb (six), lower-limb (seven), or combined (seven) exercise group. The upper-limb group trained with a circuit of upper-limb exercises, the lower-limb group by walking, and the combined group with both. Exercise was for one hour three times per week for eight weeks. Assessment before and after training included pulmonary function, mouth pressures, respiratory muscle endurance, maximal bicycle exercise test, maximal and submaximal arm ergometer, six-minute walking distance, and a scale of well-being (Bandura scale). Twenty-six patients completed the program. There was a significant improvement (Wilcoxon rank sum test) in the following: six-minute walking distance in the lower-limb (p less than 0.005) and combined (p less than 0.003) groups; arm ergometer in the upper-limb (p less than 0.005) and combined (p less than 0.04) groups; and the scale of well-being in the combined (p less than 0.005) group. There was no significant change in any other parameter measured. We conclude that exercise training improves exercise performance in severe CAO, that the training is specific for the muscle group trained, and that upper-limb exercises should be included in training programs for these patients.

Aged↗

The incidence of malignant mesothelioma in Australia, 1947-1980.

Details of patients with malignant mesothelioma that was diagnosed in Australia before 1981 were obtained by searching all possible sources throughout Australia as far into the past as possible and up to and including 1980. The earliest patient with mesothelioma who was identified was diagnosed in Victoria in 1947. By 1980, 535 (81%) men and 123 (19%) women had been diagnosed with the disease; only 14 persons were aged less than 35 years at the time of diagnosis (the youngest person was 15 years of age). The incidence rate in subjects who were 35 years or older at diagnosis was less than 1.0 cases per million person-years until 1964-1968, and then it rose progressively to 15.5 cases per million person-years in 1979-1980. The highest rate (69.7 cases per million person-years) was observed in 65- to 74-year-old men in 1979-1980. The incidence rate in Western Australia was greater than were the rates in other states of Australia after the mid 1960s. Pleural mesotheliomas accounted for 88% of cases in which the site of the tumour was known; peritoneal mesotheliomas accounted for 10% of such cases and "other" sites for 2% of such cases. In 6% of cases the site was not specified. The exposure to asbestos was stated as "definite" in 59% of the cases with a recorded history of exposure: 8% of all the cases in the study had been exposed to crocidolite (blue asbestos) from Wittenoom Gorge in Western Australia. The age at diagnosis of patients with known exposure to asbestos was similar to that in those without known exposure. The increases in the incidence of malignant mesothelioma in Australia follow the published trends in the production and use of the amphibole varieties of asbestos in this country after a lag period of between 20 and 30 years.

Adolescent↗

Indomethacin augments lymphokine-activated killer cell generation by patients with malignant mesothelioma.

Human malignant mesothelioma (MM) cells are resistant to natural killer (NK) cell lysis but susceptible to lysis by lymphokine-activated killer (LAK) cells from control individuals. The present study was performed to determine the capacity of patients with MM (n = 22) and individuals occupationally exposed to asbestos (the major population at risk of developing this disease, n = 52) to generate LAK cells capable of effectively lysing human mesothelioma cells. Compared to controls (n = 20), both patient groups demonstrated significantly depressed LAK cell activity against mesothelioma tumor cell targets (55 +/- 3% lysis by controls vs 34 +/- 3% lysis by patients with MM, P less than 0.005; and 45 +/- 3% lysis by asbestos-exposed individuals, P less than 0.025). Addition of 10 micrograms/ml indomethacin during LAK cell generation restored normal LAK cell activity for patients with MM (52 +/- 6% lysis of cultured human MM cells, P = NS compared to controls), suggesting that the defective cytolytic cell function observed in some patients with MM is a result of prostaglandin-induced immunosuppression. The ability of indomethacin to restore suppressed LAK cell activity in patients with MM suggests that the concomitant use of this agent in ex vivo LAK cell generation and in patients undergoing interleukin/LAK cell therapy may be beneficial.

Asbestos↗

Natural history of pleural thickening after exposure to crocidolite.

Serial plain chest radiographs of 384 men who worked at the Wittenoom crocidolite mine and mill between 1943 and 1966 and who applied for pneumoconiosis compensation between 1948 and 1982 have been examined independently by two trained observers for pleural disease using the 1980 ILO-UICC classification of radiographs to record width and extent of pleural disease. Radiographs covering follow up periods of from two to 38 years were examined (median number of films per subject was nine). The degree of crocidolite exposure was estimated from employment records and a survey of airborne fibre concentrations performed in 1966. Agreement between the observers on the presence and degree of pleural disease in the final film for each subject was moderately close (Kendall's tau B = 0.62) and was least for subjects with thickening less than 5 mm in width. Diffuse pleural thickening extending for greater than 50% of the lateral chest wall was the most common type recorded by both observers. Minor pleural thickening frequently progressed in extent along the lateral chest wall but progression beyond 5 mm in thickness was less common. Pleural plaques were not seen to progress beyond their initial thickness or extent. The rate of onset of thickening in this population increased continually from the time of first exposure and also increased slightly with age. There was evidence that the level of total cumulative exposure to crocidolite increased the rate of onset of pleural thickening in the period between five and 15 years after first exposure. Rate of progression of established thickening was greatest in subjects who first developed thickening early after first exposure. The relative rate of progression decreased slowly with time from first signs of thickening and there was no evidence of any progression more than 15 years after onset.

Asbestos↗

Cancer mortality in relation to measures of occupational exposure to crocidolite at Wittenoom Gorge in Western Australia.

The separate and combined effects of duration and intensity of exposure to crocidolite on mortality from lung cancer, malignant mesothelioma, and stomach cancer were examined in 6506 male former crocidolite miners and millers at Wittenoom Gorge, Western Australia. Each subject who had died from lung cancer (92), mesothelioma (31), or stomach cancer (17) was matched with up to 20 control subjects of the same age who were not known to have died before the index subject. Relations of dose and time of exposure to crocidolite to risk of death were modelled by conditional logistic regression. For lung cancer, the best fitting multiplicative model was one which estimated a relative risk (RR) of 1.12 (95% CI 1.04-1.20) per year of exposure and 1.01 (95% CI 1.00-1.01) per fibre/ml. This was statistically indistinguishable from an additive model showing an increase in RR of 0.01045 (95% CI 0.008-0.020) per f/ml year. For mesothelioma the best fitting model appeared to be one estimating a RR of 24.9 (95% CI 3.51-1.77) per log year since first exposed and a RR of 10.5 (95% CI 3.12-35.1) if exposed for longer than six months. This was not distinguishable statistically from a model that showed mortality increasing as the fourth power of time since first exposed less the fourth power of time since last exposed. The effect of intensity of exposure on the RR for mesothelioma was only slight. There was no consistent effect of any measure of exposure to crocidolite on death from stomach cancer.

Asbestos↗

Respiratory symptoms, lung function, and sensitisation to flour in a British bakery.

A survey of dust exposure, respiratory symptoms, lung function, and response to skin prick tests was conducted in a modern British bakery. Of the 318 bakery employees, 279 (88%) took part. Jobs were ranked from 0 to 10 by perceived dustiness and this ranking correlated well with total dust concentration measured in 79 personal dust samples. Nine samples had concentrations greater than 10 mg/m3, the exposure limit for nuisance dust. All participants completed a self administered questionnaire on symptoms and their relation to work. FEV1 and FVC were measured by a dry wedge spirometer and bronchial reactivity to methacholine was estimated. Skin prick tests were performed with three common allergens and with 11 allergens likely to be found in bakery dust, including mites and moulds. Of the participants in the main exposure group, 35% reported chest symptoms which in 13% were work related. The corresponding figures for nasal symptoms were 38% and 19%. Symptoms, lung function, bronchial reactivity, and response to skin prick tests were related to current or past exposure to dust using logistic or linear regression analysis as appropriate. Exposure rank was significantly associated with most of the response variables studied. The study shows that respiratory symptoms and sensitisation are common, even in a modern bakery.

Adult↗

Preoperative assessment as a predictor of mortality and morbidity after lung resection.

To refine the functional guidelines for operability for lung resection, we prospectively studied 55 consecutive patients with suspected lung malignancy thought to be surgically resectable. Lung function and exercise capacity were measured preoperatively and at 3 and 12 months postoperatively. Preoperative pulmonary scintigraphy was used to calculate the contribution to overall function by the affected lung or lobe and to predict postoperative lung function. Pneumonectomy was performed in 18 patients, lobectomy in 29, and thoracotomy without resection in six. No surgery was attempted in two patients who were considered functionally inoperable. Cardiopulmonary complications developed in 16 patients within 30 days of surgery, including three deaths. The predictions of postoperative function correlated well with the measured values at 3 months. For FEV1, r = 0.51 in pneumonectomy (p less than 0.05) and 0.89 in lobectomy (p less than 0.001). Predicted postoperative FEV1 (FEV1-ppo), diffusing capacity (DLCO), predicted postoperative DLCO (DLCO-ppo) and exercise-induced arterial O2 desaturation (delta SaO2) were predictive of postoperative complications including death and respiratory failure. In patients who underwent pneumonectomy, the best predictor of death was FEV1-ppo. The predictions were enhanced by expressing the value as a percentage of the predicted normal value (% pred) rather than in absolute units. For the entire surgical group a FEV1-ppo greater than or equal to 40% pred was associated with no postoperative mortality (n = 47), whereas a value less than 40% pred was associated with a 50% mortality (n = 6), suggesting that resection is feasible when FEV1-ppo is greater than or equal to 40% pred.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Gallium lung scanning and bronchoalveolar lavage in crocidolite-exposed workers.

Gallium lung scanning is widely used to evaluate pulmonary inflammation in patients with interstitial lung disease but has not previously been reported in crocidolite-exposed workers. In order to characterize the pulmonary inflammation caused by crocidolite inhalation, GLS and BAL findings were related to chest x-ray film changes graded according to the ILO classification of roentgenograms of pneumoconioses. In individuals with roentgenographic evidence of asbestosis (CXR greater than or equal to 1/0, n = 15), 13 had a positive GLS and 13 had an abnormal BAL. In asbestos-exposed individuals with equivocal chest x-ray film changes (CXR 0/1, n = 12), six had a positive GLS and six had BAL changes (both GLS and BAL abnormal in three). In individuals with a normal chest x-ray film (CXR 0/0 n = 8), two had a positive GLS and two BAL changes (both abnormal in 1). These data demonstrate that most subjects with crocidolite-induced asbestosis have an abnormal GLS and BAL. In addition, many individuals with asbestos exposure and equivocal or no chest x-ray film changes have an abnormal GLS and/or BAL, suggesting the presence of active subclinical pulmonary inflammation in these individuals.

Asbestos↗

Radiographic abnormalities and duration of employment in Western Australian iron-ore miners.

Plain chest radiographs of 788 Pilbara iron-ore miners from Western Australia have been examined by two independent observers for evidence of pneumoconiosis. The prevalence of any radiographic abnormality (a profusion grade of 0/1 or greater on the International Labour Office [ILO] scale) was 6.7% for Reader 1 and 9.9% for Reader 2. The prevalence of a definite radiographic abnormality (a profusion grade of 1/0 or greater on the ILO scale) was 1.9% for Reader 1 and 2.8% for Reader 2. The prevalence of any abnormality, as identified by either or by both observers, was significantly related to age. The relationship between a radiographic abnormality and the duration of employment was less clear. The results indicate a need for more detailed and comprehensive studies of the effects of iron-ore dust in this industry.

Adolescent↗

Isocyanates and respiratory disease: current status.

This paper reviews the known respiratory effects of isocyanates. There is good evidence to indicate that isocyanates: cause chemical bronchitis/pneumonitis; are potent pulmonary sensitizers capable of causing "isocyanate asthma"; cause nonspecific airways disease, including chronic bronchitis; can induce a general asthmatic state; and can cause hypersensitivity pneumonitis. Similar dose-response relationships are seen for both acute and chronic effects. There are plants operating in which exposures are well controlled and in which no respiratory effects can be detected. Suggestions are provided for preplacement assessment and periodic surveillance for workers exposed to these compounds.

Air Pollutants, Occupational↗

Bronchoalveolar lavage sampling of airway and alveolar cells.

Bronchoalveolar lavage (BAL) cell counts are used to assess 'alveolitis' in patients with interstitial lung diseases (ILD) but inflammatory cells from airways can contribute to the differential cell count. To determine what BAL volume samples airway cells in patients with ILD we measured the proportion of bronchial epithelial cells (BECs) in four successive 25 ml aliquots in a single lung subsegment in 23 patients with ILD (cryptogenic fibrosing alveolitis (CFA) four, rheumatoid lung (RL) three, asbestosis (ASB) 11, sarcoidosis (SARC) five). Cells recovered from the first two 25 ml lavages exhibited higher proportions of BECs (15 +/- 4% and 9 +/- 2% respectively) than those from the remaining two aliquots (3 +/- 1%, 3 +/- 1%, each P less than 0.01), suggesting that the first 50 ml BAL preferentially samples airway cells compared to the second 50 ml BAL. To evaluate airway and alveolar inflammatory cell proportions in ILD we performed two separate 50 ml BALs (samples I and II) in a single subsegment in 38 patients with ILD (CFA seven, RL five, ASB 19, SARC seven) and measured the proportions of recovered cells in each sample separately and combined. Seven control individuals were also studied. Sample I contained 1-67% (mean 26 +/- 3%) of the total recovered cells. Neutrophil (PMN) proportions were higher in sample I compared to sample II in CFA (20 +/- 6 vs 8 +/- 2%), RL (30 +/- 9 vs 8 +/- 2%) and ASB (12 +/- 2 vs 7 +/- 1%), P less than 0.05 for each, but were similar in samples I and II in patients with SARC (3 +/- 1 vs 2 +/- 1%) and controls (2 +/- 1 vs 2 +/- 1%). In combined samples (I + II), absolute PMN proportions were up to 8% higher than in sample II alone whereas absolute lymphocyte proportions were up to 8% less than in sample II alone. These data suggest that separate processing of the fluid recovered from the first 50 ml BAL in ILD patients provides information on the location of inflammatory cells and improves the accuracy of BAL cell counts.

Adult↗

Mortality in miners and millers of crocidolite in Western Australia.

It is known that 6505 men and 411 women were employed in the mining and milling of crocidolite at Wittenoom in the Pilbara region of Western Australia between 1943 and 1966. Employment was usually brief (median duration four months) and exposure intense (median estimated cumulative exposure 6 fibres/cc years). The vital status of 73% of the men and 58% of the women employed in the industry was known at 31 December 1980, providing 95 264 person-years of follow up with 820 deaths in men and 4914 person-years with 23 deaths in women. The standardised mortality ratio (SMR) for all causes in men was 1.53 (95% confidence interval 1.43 to 1.64). Statistically significant excess death rates were observed in men for neoplasms, particularly malignant mesothelioma (32 deaths), neoplasms of the trachea, bronchus, and lung (SMR 2.64), and neoplasms of the stomach (SMR 1.90); respiratory diseases, particularly pneumoconiosis (SMR 25.5); infections, particularly tuberculosis (SMR 4.09); mental disorders particularly alcoholism (SMR 4.87); digestive diseases, particularly peptic ulceration (SMR 2.46) and cirrhosis of the liver (SMR 3.94); and injuries and poisonings, particularly non-transport accidents (SMR 2.36). The excess mortality from pneumoconiosis, malignant mesothelioma, and respiratory cancers, but not stomach neoplasms, was dependent on time since first exposure and cumulative exposure. There was no increase in mortality from laryngeal cancer (SMR 1.09) or neoplasms other than those listed. The SMR for all causes in women was 1.47 (95% confidence interval 0.98-2.21) and for neoplasms 1.99; there was one death from malignant pleural mesothelioma.

Adult↗

Pulmonary disease from exposure to an artificial aluminium silicate: further observations.

A cross sectional analysis of the relation between exposure to an artificial aluminium silicate (alunite residue) and pulmonary function changes has been made in 32 subjects, 17 of whom had been previously reported and in whom there was suggestive evidence of a dose response relation between gas transfer and total silicate exposure. Longitudinal data were also available for nine subjects. No dose effect relation was observed in either analysis and only one of the three subjects previously observed to have an abnormal chest radiograph (the index subject) had deteriorated appreciably. Respirable particles of alunite residue were injected intratracheally into Syrian hamsters. No evidence of pulmonary toxicity was seen as judged by bronchoalveolar lavage measurements of the concentrations lactic dehydrogenase, albumin, and the lambda fraction of gold, and the numbers of macrophages, polymorphonuclear cells, and red blood cells (alpha-quartz and ferrous oxide were used as positive and negative controls). These results do not support a significant toxic effect of this aluminium silicate on the lungs.

Adolescent↗

Occupational asthma in a mineral analysis laboratory.

An epidemic of symptoms suggestive of occupational asthma in workers in a mineral analysis laboratory necessitating exposure to vapours of hydrochloric, hydrofluoric, nitric, perchloric, and sulphuric acid solutions was investigated. Variable airflow obstruction was confirmed by serial measurement of FEV1 in two subjects who showed 18% and 22% fall in FEV1 during a workshift. Of a workforce of 21 laboratory staff, 20 took part in a study of ventilatory capacity and bronchial reactivity. All but one subject had normal ventilatory capacity but five had bronchial hyperreactivity (PC20 less than or equal to 8 mg/ml histamine). Four of the five with hyperreactivity had a history of chest tightness at work whereas only two subjects with chest tightness had PC20 greater than 8 mg/ml (p less than 0.01). Other work related symptoms were cough (two subjects) and breathlessness (three subjects). Four of the subjects with bronchial hyperreactivity were atopic, suggesting that hyperreactivity may have predated exposure to irritant material at work and resulted in their being susceptible to the development of symptoms and raises the possibility of identifying susceptible subjects by preplacement examination. In two of these subjects, however, bronchial reactivity has returned to normal after 205 and 376 days away from work, suggesting that bronchial inflammation resulted from occupational exposure to acid vapours.

Acids↗

Bronchial responsiveness, lung mechanics, gas transfer, and corticosteroid response in patients with chronic airflow obstruction.

Thirty patients with stable chronic airflow obstruction receiving regular bronchodilator treatment were studied to determine whether the level of bronchial responsiveness, transfer factor for carbon monoxide (TLCO), or the mechanical properties of the lung predicted a bronchodilator response to oral corticosteroid treatment. Before treatment mean (SD) FEV1 was 48% (16%) of the predicted value (% pred); the geometric mean concentration of methacholine required to produce a 20% fall in FEV1 (PC20) was 0.44 (range 0.07-3.32) mg/ml; and TLCO was 59% (21%) predicted. The exponential constant (k) defining the shape of the static volume-pressure curve was 146% (66%) predicted and pulmonary conductance relative to predicted lung volume at a transpulmonary pressure of 5 cm H2O (sGL5) was 72% (37%) predicted. After prednisolone treatment (0.6 mg kg-1 day-1 for two weeks) FEV1 increased by 8% (19%) (p less than 0.05) and daily mean peak flow (PEF) by 3% (10%) (p less than 0.01) over pretreatment values. Three patients had an increase in FEV1 of more than 30%, two of whom had sputum eosinophilia (p less than 0.05). The three were among the 13 patients with a reduced sGL5. The increase in FEV1 did not correlate with initial PC20 (r = 0.16), k (r = -0.12), or TLCO (r = -0.14). Thus measurements of bronchial responsiveness, lung distensibility, and TLCO did not predict corticosteroid response in patients with stable chronic airflow obstruction. Patients with sputum eosinophilia or reduced pulmonary conductance may be more likely to respond.

Airway Resistance↗

Functional similarities of asbestosis and cryptogenic fibrosing alveolitis.

The pathological features in the lung in asbestosis and cryptogenic fibrosing alveolitis are similar. Patients with asbestosis, however, appear to have less severe impairment of transfer factor (TLCO) than those with fibrosing alveolitis for a given level of radiographic abnormality when assessed on the basis of the International Labour Organisation (ILO) profusion score. The impairment of lung function in the two disorders has been compared in more detail in 29 patients with asbestosis and 25 with fibrosing alveolitis, arterial oxygen desaturation during exercise being used to define the severity of the disorders. Arterial oxygen saturation (ear oximeter) and oxygen uptake were measured during incremental exercise on a cycle ergometer. TLCO (single breath technique) and total lung capacity (TLC, plethysmograph) were measured. Chest radiographs were graded for profusion according to the ILO international classification. Patients with asbestosis had significantly higher mean values for TLCO and TLC and lower mean profusion scores than those with fibrosing alveolitis. When stratified for the degree of arterial oxygen desaturation, however, no significant differences were found in TLCO, TLC, or profusion score between the two disorders. To the extent that arterial oxygen desaturation with exercise reflects the morphological severity of the disease, these results suggest that, for a given degree of interstitial lung disease, asbestosis and cryptogenic fibrosing alveolitis are functionally and radiologically similar.

Asbestosis↗