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Biomedical subjects

A W Musk

Publications and source records attributed to A W Musk.

At least 73 records · Page 4Linked to original sources
PubMed1996

Comparison of measures of exposure to asbestos in former crocidolite workers from Wittenoom Gorge, W. Australia.

Determinations of exposure-response relationships between crocidolite and the major asbestos-related diseases in the Wittenoom cohort have previously depended on the validity of estimates of airborne exposure to asbestos. This work aims to validate the airborne exposure measurements by obtaining measurements of the concentrations of uncoated crocidolite fibers and asbestos bodies retained in the lungs of individual workers, and to estimate the half-life of crocidolite fibers in the lungs. Samples of lung tissue, excluding tumor, of all former Wittenoom workers known to have died in Western Australia (WA) were sought from teaching hospitals, pathology departments, and the Coroner's pathologist. The lung specimens were processed using Pooley's method with TEM for counts of fibers of all types and using Smith and Naylor's method with conventional light microscopy for asbestos bodies (AB). Multiple linear regression was utilized to examine the associations between crocidolite concentrations in the lung and duration of employment at Wittenoom, time since last employed at Wittenoom, nature of job, estimated average fiber concentration at the worksite, and estimated cumulative crocidolite exposure (CCE) in fiber-years/ml for each subject. Lung tissue from 90 cases was processed and there was good agreement between counts of crocidolite fibers, asbestos bodies, and CCE. Correlations were 0.77 for AB and fibers, 0.54 for AB and CCE, and 0.58 for CCE and fibers, after log transformation. The half-life of crocidolite fibers in the lung was estimated at 92 months (95% CI 55-277 months). Previous estimates of airborne exposure to Wittenoom crocidolite have been reasonably reliable. The relatively simple technique of light microscopy for counting ABs in lung tissue also provides a useful and reliable indication of the level of past occupational exposure to crocidolite in subjects whose exposure has been only to crocidolite. The half-life of crocidolite fibers in the lungs of former Wittenoom workers is about 7-8 years.

Adult↗
PubMed1996

Exposure to crocidolite and the incidence of different histological types of lung cancer.

OBJECTIVES: To estimate the relations between exposure to both tobacco smoke and crocidolite and the incidence of various histological types of lung cancer. METHODS: In 1979 all former workers from the Wittenoom asbestos industry who could be traced were sent a questionnaire on smoking history. Of 2928 questionnaires sent, satisfactory replies were received from 2400 men and 149 women. Of the men, 80% had smoked at some time and 50% still smoked. Occupational exposure to crocidolite was known from employment records and follow up was maintained through death and cancer registries in Australia with histological diagnoses obtained from the relevant State Cancer Registry. Conditional logistic regression was used to estimate the effects of tobacco and asbestos exposure on incidence of different cell types of lung cancer in a nested case-control design. RESULTS: Between 1979 and 1990, 71 cases of lung cancer occurred among men in this cohort: 27% squamous cell carcinoma, 31% adenocarcinoma, 18% small cell carcinoma, 11% large cell carcinoma, and 13% unclassified or indeterminate. Two of the classified cases and one unclassified case had never smoked. The incidence of both squamous and adenocarcinoma types of lung cancer were greatest in ex-smokers and in those subjects with the highest levels of exposure to crocidolite. After adjustment for smoking habit, the increase in incidence of lung cancer with increasing exposure to crocidolite was greater for squamous cell carcinoma than for adenocarcinoma. CONCLUSIONS: The results from this study have shown significant exposure-response effects for exposure to crocidolite, and both adenocarcinoma and squamous cell carcinoma of the lung. They also provide some further evidence against the theory that parenchymal fibrosis induced by asbestos is a necessary precursor to asbestos induced lung cancer.

Adenocarcinoma↗
PubMed1995

Fc epsilon RI-beta polymorphism and risk of atopy in a general population sample.

OBJECTIVE: To establish the prevalence of Fc epsilon RI-beta polymorphisms Leu181 and Leu181/Leu183 on chromosome 11q13 in the general population and to examine whether when maternally inherited they confer a risk of atopy. DESIGN: A population based survey for measures of atopy (skin prick test reactions, specific IgE titres, total serum IgE concentration), bronchial hyperresponsiveness, and carriage of Fc epsilon RI-beta Leu181 and Leu181/Leu183. SETTING: The rural coastal town of Busselton, Western Australia. SUBJECTS: 1004 members of 230 two generation families identified through adults aged under 55. RESULTS: Fc epsilon RI-beta Leu181/Leu183 was identified in 45 subjects (4.5%). All 13 children who had inherited the variant maternally were atopic. Six had asthma and nine rhinitis. The odds ratio of a positive skin prick test reaction to house dust mite or grass pollen in these children compared with the other 523 children was 7.37 (95% confidence interval 1.62 to 33.60). The 95% confidence interval for the odds ratio of a positive specific IgE response (radio-allergosorbent test) was 3.00 to infinity, and the odds ratio for bronchial hyperresponsiveness was 3.70 (1.21 to 11.60). By contrast, the eight children who had derived the variant paternally had negative skin prick and radioallergosorbent test results and did not have increased bronchial responsiveness. CONCLUSION: Fc epsilon RI"' beta Leu181/Leu183 when inherited maternally identifies a genetic risk factor for atopy and bronchial hyperresponsiveness.

Adolescent↗
PubMed1995

Asbestos bodies in lung tissue following exposure to crocidolite.

A series of 206 necropsies in Western Australia (WA) have had routine counts made of asbestos bodies in samples of lung tissue using conventional light microscopy. Thirty-two cases had worked in the asbestos industry at Wittenoom, WA and (log) counts of asbestos bodies in their lung tissue correlated well with estimates of their (log) cumulative airborne exposure to crocidolite fibers (r = 0.60). There was no association between the number of asbestos bodies and time since exposure to asbestos ceased. In subjects without known exposure to asbestos, there was a weak but nonsignificant increase in number of asbestos bodies with increasing age, with 26% of cases having no asbestos bodies present. It is concluded that the relatively simple technique of light microscopy for counting of asbestos bodies in lung tissue provides a reliable indication of the level of past occupational exposure to crocidolite in subjects whose exposure has been only to crocidolite. This could be extremely useful in follow-up studies of cohorts that lack reliable measures of airborne exposure to crocidolite asbestos.

Adult↗
PubMed1995

Detection of a recessive major gene for high IgE levels acting independently of specific response to allergens.

The genetic control of the total IgE, the immunoglobulins E involved in allergy, remains still unclear. Although high IgE levels were found to be determined by a recessive major gene in several studies, other modes of inheritance were also reported. Moreover, at least two different genetic mechanisms controlling the IgE regulation have been suggested: one involved in the specific IgE response and the other one in the nonspecific response. To better understand the genetic mechanisms controlling IgE variation, we performed segregation analysis of IgE levels by ignoring or taking into account the specific response to allergens (SRA). Analyses were conducted using the class D regressive model, in a sample of 234 Australian nuclear families randomly selected during the winter months, when IgE levels are the lowest (basal). SRA, when included as a covariate in the model, was defined by one of the three following criteria: (1) raised specific IgE level for one or more allergens, (2) positive skin test for one or more allergens, and (3) at least one of the (1) or (2) criteria. When the presence of SRA is ignored, the familial transmission of total IgE level is compatible with the segregation of a recessive major gene and residual familial correlations. When the presence of SRA is accounted for in the analysis, whether defined by criteria (1), (2), or (3), there is still evidence for a recessive major gene controlling IgE levels but residual familial correlations are no longer significant. In addition, no interaction between this major gene and SRA is shown here. Our results suggest that this gene, which accounts for 28% of the variation of the trait, may be involved in the control of basal IgE production, independently of specific response to allergens.

Adolescent↗
PubMed1995

Potential for interferon-alpha-based therapy in mesothelioma: assessment in a murine model.

Malignant mesothelioma is an aggressive tumor, usually induced by asbestos exposure, that has a poor prognosis and is unresponsive to conventional therapy. The present study was aimed at assessing the potential for interferon-alpha (IFN-alpha)-based therapies in a murine model for malignant mesothelioma. The effect of recombinant human IFN-alpha B/D on tumor growth, alone and in combination with either of two immunomodulatory and antiproliferative agents beta-carotene or alpha-difluoromethylornithine (DFMO), was assessed. The data suggest that IFN-alpha treatment is most efficacious when commenced early in tumor development. Combination of IFN-alpha with either DFMO or dietary beta-carotene supplementation improved the effect of an otherwise suboptimal IFN-alpha therapy regimen. Both IFN-alpha and beta-carotene had in vivo stimulatory effects on immune cells, perhaps indirectly by inhibiting TGF-beta generation. The immunomodulatory effects may contribute, at least in part, to the positive antitumor and clinical activities of the treatments in this model.

Adjuvants, Immunologic↗
PubMed1995

Malignant mesothelioma in Pilbara Aborigines.

Malignant mesothelioma occurred in a female Aborigine after environmental exposure to asbestos. All known cases of the disease in Aborigines in Western Australia were reviewed; all occurred in Pilbara residents. Most were exposed while involved in the transport of asbestos from the Wittenoom crocidolite operation. Based on recent estimates of the size of the Aboriginal population in the Pilbara region, their incidence of this disease (250 per million for ages 15 and over) is one of the highest population-based rates recorded.

Adult↗
PubMed1995

Preliminary study of lung cancer mortality among Western Australian gold miners exposed to silica.

Gold miners from Western Australia were surveyed in 1961. Data were collected on respiratory symptoms, smoking habits, employment history, and chest X-ray signs. Eighty-four percent of the men had smoked at some time, and 66% were current smokers. The prevalence of chronic bronchitis was over 20% at the time of the survey. A follow-up to the end of 1991 has been started which showed that, from 1969 to 1991, 999 miners died. Because vital status has not been ascertained for the whole cohort, a proportional mortality analysis was undertaken as a case-referent study. A strong effect of smoking on the risk of lung cancer was found, along with a slight, but nonsignificant increase in the lung cancer risk for the subjects employed underground for > or = 40 years after adjustment for smoking. A complete follow-up and a full cohort analysis will enable these effects to be estimated more precisely.

Aged↗
PubMed1994

Genetic linkage of T-cell receptor alpha/delta complex to specific IgE responses.

IgE responses to inhaled proteins underlie the clinical syndrome of allergic (atopic) asthma and rhinitis. We have investigated genetic linkage between specific IgE reactions to highly purified major allergens and the T-cell receptor (TCR) alpha and beta gene complexes on chromosome 14 and 7, respectively. Antigens tested included highly purified proteins from the housedust mite Dermatophagoides pteronyssinus, the domestic cat and dog, grass pollen, and the mould Alternaria alternata. Affected sibling-pair methods were used in two independent sets of families, one in the UK and one in Australia. No linkage of IgE serotypes to TCR-beta was detected, but significant linkage to TCR-alpha was seen in both family groups. For several of the IgE phenotypes investigated (positive responses to whole allergen sources or purified antigens or serum IgE above the 70th percentile in the population) the affected sibling-pairs showed significant sharing of TCR-alpha microsatellite alleles from both parents. The results show that a gene (or genes) in the TCR-alpha region modifies specific IgE responses.

Alleles↗
PubMed1994

Progress on smoking control in Western Australia.

In 1990, 20 years of campaigning by the Western Australian branch of the Australian Council on Smoking and Health succeeded in getting tobacco advertising banned in Western Australia and a fund set up to replace the sponsorship of sport by tobacco companies. The council coordinated the activities of the mainly professional medical organisations that formed its members, ensuring that messages about the dangers of tobacco were consistently presented from different angles. The campaigners also ensured that medical data were reworked for presentation to decision makers and public, invaded the corporate world, and minimised opposition by enlisting the support of sportspeople opposed to tobacco sponsorship. The council hopes now that elimination of advertising will reduce the prevalence of smoking.

Advertising↗
PubMed1993

Malignant mesothelioma after environmental exposure to blue asbestos.

To determine the magnitude of the population at risk from non-occupational exposure to crocidolite at Wittenoom, Western Australia (WA), a cohort of 4,890 residents who never worked for the mining company Australian Blue Asbestos (ABA) has been assembled from all 18,553 available records: the local school register, hospital attendances, the WA electoral roll, birth certificates, workers who answered a mailed questionnaire in 1979, participants in a cancer-prevention programme using vitamin-A dietary supplements, and other sources. The majority of subjects were relatives and friends of ABA employees, and nearly half the cohort were either born at Wittenoom or first went there as children under 10 years of age. As most residents were at Wittenoom when the mine and mill were in operation during the period 1943 to 1966, 82% were first exposed to crocidolite 20 or more years ago. The proportion of other workers (i.e., not employed by ABA) and their families increased once the mining operations ceased. To date, 24 cases of mesothelioma have been reported in this cohort: 9 males and 15 females. Time from first exposure to diagnosis ranged from 23 to 44 years and residence in Wittenoom ranged from 6 weeks to 11 years.

Adolescent↗
PubMed1993

Effect of interferon-alpha 2a on malignant mesothelioma.

Malignant mesothelioma (MM) is a tumor that is resistant to conventional therapy. Interferon-alpha (IFN-alpha) has been used in the treatment of some human tumors, and we have previously demonstrated an in vitro anti-proliferative effect of IFN against MM cell lines. Therefore, the effect of recombinant human IFN-alpha (IFN-alpha 2a) (Roferon-A, Hoffmann-La Roche) on previously untreated patients with MM has been studied. Twenty-five patients (24 male and 1 female), with a mean age of 59 +/- 9.9 years, were treated for 3 months with IFN-alpha 2a. The starting dose was 3 x 10(6) IU daily increasing to a maximum of 18 x 10(6) IU daily or as tolerated. All patients had measurable tumor on thoracic CT prior to commencement. CT scans were performed at 6 and 12 weeks to determine tumor response. Twenty patients completed 3 months of treatment. Five patients were withdrawn because of disease progression. Side effects were predictable and dose related. Dose reductions were necessary in 12 patients for grade 2 toxicity. One patient had a complete response (CR), 2 patients had partial responses (PR) (response rate = 12%), 13 (52%) patients remained stable, 1 of whom exhibited a delayed PR, and 9 (36%) had progressive disease. These data suggest that IFN-alpha 2a is well tolerated in patients with MM and is active against MM in a proportion of patients.

Aged↗
PubMed1993

Interferon alpha and doxorubicin in malignant mesothelioma: a phase II study.

BACKGROUND: Malignant mesothelioma is a tumour which is generally resistant to chemotherapy. While the addition of interferon to chemotherapy improves response rates in some other malignancies, such a combination has not been evaluated in the treatment of mesothelioma. AIMS: To assess the anti-tumour effects and toxicity of interferon-alpha combined with doxorubicin in the treatment of pleural mesothelioma. METHODS: Twenty five patients (mean age 54 +/- 11 years) were enrolled in a phase II study. All patients had a confirmed histological diagnosis, measurable tumour, a life expectancy of at least three months, and no prior chemotherapy or interferon. Interferon alpha-2a, 9 x 10(6) U sc daily, was administered together with doxorubicin 25 mg per m2 i.v. weekly, for 12 weeks. Response status was assessed by tumour measurements on clinical examination and thoracic CT scans before and after treatment. RESULTS: A partial response was observed in four patients (16%; 90% CI, 8-30%), 11 remained stable, while six had progressive disease. Four patients withdrew within the first month because of toxicity. The median survival of all patients was 11 months (95% CI, 3-19). Dose modification as a result of toxicity was required in all patients. Lethargy, weight loss, leukopenia and vomiting were the most common side effects. CONCLUSIONS: The combination of interferon-alpha and doxorubicin showed only modest activity and was associated with significant toxicity. It cannot be recommended in the treatment of malignant pleural mesothelioma.

Combined Modality Therapy↗