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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
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

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↗
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↗