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Biomedical subjects

M Turner-Warwick

Publications and source records attributed to M Turner-Warwick.

At least 127 records · Page 7Linked to original sources

Bronchoalveolar lavage fluid cell counts in cryptogenic fibrosing alveolitis and their relation to therapy.

Bronchoalveolar lavage was used to sample inflammatory cells from the lungs of 51 patients with cryptogenic fibrosing alveolitis (CFA) (24 smokers, 12 ex-smokers, and 15 non-smokers). The smokers with CFA have been compared with 15 smoking control subjects in whom there was no radiographic abnormality or clinical evidence of chronic bronchitis. Significantly lower volumes of lavage fluid were recovered from the smokers with CFA (p < 0.001) and the fluid contained lower percentages of macrophages (p < 0.01), reflecting increased percentages of eosinophils (p < 0.001) and neutrophils (p < 0.01). Similar changes were seen in the ex-smokers and non-smokers. There was also an increase in the percentages of lymphocytes when the whole group of CFA patients was compared with the control subjects (p less than or equal to 0.05). No significant differences were found when patients with "lone" CFA were compared with those having associated systemic disease. The only feature distinguishing smokers from non-smokers with CFA was the presence of pigmented cytoplasmic inclusions in the macrophages from the smokers (p < 0.001). However, there were lower numbers of pigmented macrophages in the smoking CFA patients by comparison with the control subjects suggesting either a change in phagocytic capacity or turnover rate in this disease. Profiles of differential cell counts in individual patients showed that increases of eosinophils over 3% or neutrophils over 4% or both with lymphocyte counts of less than 11% related to a poor clinical response to corticosteroids, but lymphocyte percentages greater than 11% related to improvement (p < 0.05).

Adult↗

Cryptogenic fibrosing alveolitis and lung cancer.

Lung cancer was found in 20 (9.8%) of 205 patients with cryptogenic fibrosing alveolitis (CFA) or 12.9% of the 155 patients in this series followed to death. An excess relative risk of lung cancer of 14.1 was found in patients with CFA compared to the general population of comparable age and sex, allowing for the lengths of follow-up of the CFA patients. The relative risk for male smokers was (observed/expected) 15+1.06 = 14.2, and for female smokers (O/E) 2/0.3 = 6.7. Only one male and one female non-smoker had lung cancer. These data suggest that there is an excess risk of lung cancer not wholly accounted for by age, sex, or smoking habit. The distribution of histological types was not obviously different from that found in lung cancer without pulmonary fibrosis. Large opacities suggestive of lung cancer were present at the time of first hospital attendance for symptoms relating to CFA in four of the 20 patients. Finger clubbing was present in 19 (95%) compared with 116/185 (63%) of those so far not developing cancer. There were no other clinical differences at presentation. In particular, cancer was not found especially in those with longer survival from the onset of symptoms of CFA or with a greater initial radiographic change.

Adolescent↗

Maximal expiratory flow volume curves in workers exposed to asbestos.

We have studied 40 workers with varying industrial exposure to asbestos, using routine spirometry and maximal expiratory flow volume curves (MEFVC). Abnormalities of MEFVC were common and seen in those with normal spirometry and total lung capacity. The high incidence of abnormal MEFVC suggests that air flow dysfunction in small airways may follow prolonged asbestos exposure. Our findings support, therefore, the idea that asbestos exposure may cause an obstruction to airflow arising particularly in small airways, and that one of the common functional abnormalities attributable to asbestos exposure is airways obstruction.

Adult↗

Radiographic progression of asbestosis: preliminary report.

In a collaborative study with the Pneumoconiosis Medical Panel, 232 asbestos workers were seen between 1967 and 1975. During this time, 50 of the 232 (21.5%) workers dies, 33 (13.8%) from respiratory disease probably related to asbestos exposure [10 (4.3%) pleural mesothelioma, three (1.3%) peritoneal mesothelioma, 10 (4.3%) asbestosis, 10 (4.3%) carcinoma of the lung]. Of the 182 survirors, 119 were recalled for other studies, and follow-up data were obtained as additional information at the same time, over a 1--7 year period. Paired radiographs were read, and 21 patients (17.6%) had worsened. As expected, the frequency of progression increased with a longer follow-up time, so that about one third of the subjects displayed progression after a minimum follow-up of 6 years. Ten of 73 patients (13.6%) had progressed in 3 years or less and may be defined as rapid progressors. No particular clinical feature distinguished clearly between progressors and nonprogressors, but there was a trend toward a greater frequency and higher titer of ANA among the progressors in this group. There was also a higher frequency of progression in those who were initially classified radiographically as 1/1 of 1/2 than in those with other initial radiographic appearances. This pilot study is now forming the basis for a larger, longer-term comprehensive survey.

Antibodies, Antinuclear↗

Aspergillus fumigatus and lung disease.

The range of clinical presentations of lung diseases associated with Aspergillus spp. is great. The conditions are very frequently misdiagnosed but errors should be avoided if the possibility of a fungal cause is considered and simple immunological tests undertaken. Often no more than skin-prick tests and serum precipitins need to be done. In many cases, fungus is not isolated from the sputum and negative results do not exclude the possibility of A. fumigatus as the causal agent. Treatment often results in marked clinical improvement and there is evidence that suppression of recurrent episodes of bronchopulmonary aspergillosis prevents progressive lung damage.

Alveolitis, Extrinsic Allergic↗

Value of measuring serum angiotensin I converting enzyme and serum lysozyme in the management of sarcoidosis.

Serum angiotensin I converting enzyme (ACE) and lysozyme have been measured in 23 controls, 115 patients with sarcoidosis, and 64 with other chest diseases. Both enzymes were significantly raised in sarcoidosis. ACE was raised above the normal range in 21 of 72 (29%) patients with definite sarcoidosis and in 17 of 38 (45%) of those who were untreated and seen within one year of presentation. The rise discriminated usefully between those with stable and progressive disease (5% and 62% respectively). Lysozyme was raised in 50 of 72 (69%) patients with sarcoidosis but also in 11 of 54 (20%) patients with other chest diseases. Discrimination between stable and progressive disease was useful only if very high levels were considered. Five patients had serial measurements after treatment with oral steroids and showed a progressive fall in levals of both enzymes, but patients with other diseases also showed a significant fall within the normal range when so treated. Measurement of these enzymes may help in the management of some cases of sarcoidosis, but results require critical interpretation.

Adult↗

Factors influencing the prevalence of asthma among first degree relatives of extrinsic and intrinsic asthmatics.

The prevalence of asthma, hay fever, and eczema was examined in first degree relatives of extrinsic (atopic) and intrinsic (non-atopic) asthmatics attending the asthma clinics of the Brompton Hospital and the Doncaster Royal Infirmary. In both the Doncaster and Brompton populations the prevalence of asthma, hay fever, and eczema was significantly higher among relatives of extrinsic than among relatives of intrinsic asthmatics. Furthermore, the prevalence of these traits tended to be higher among siblings of extrinsic probands with one or both parents affected than among siblings of probands with neither parent affected. Most importantly, the prevalence of asthma among first degree relatives was positively correlated with the prevalence of hay fever or eczema or both among relatives and with the degree of atopy in the probands. These findings are consistent with the results of previous investigations in which the expression of asthma was shown to depend on a genetic predisposition to the trait as well as exposure to environmental provoking agents. We further suggest that the presence of atopy in genetically predisposed individuals increases the risk of developing asthma.

Adolescent↗

Histocompatibility antigens in asthma: population and family studies.

One hundred and twenty-two patients with intrinsic asthma, extrinsic atopic asthma, or asthma with allergic bronchopulmonary aspergillosis were tissue typed for the HLA A, B, and C loci. No associations were found with any of the clinical groups, or with serum total IgE concentrations. Sixty-eight members of 10 families where more than one member was affected by asthma were studied. The segregation of haplotypes in siblings of the propositi who were or were not affected by asthma did not differ from the predicted segregation, and there were no differences when atopy or serum total IgE were considered. No biologically important association between HLA and asthma has been shown.

Adolescent↗

Small cell carcinoma: combined approach to treatment.

Fifty-six patients with untreated small cell carcinoma of the bronchus were treated with three courses of chemotherapy (cyclophosphamide, vincristine, and procarbazine and methotrexate) and assessed for response. Thirty-one patients (55.4%) were classified as responders; they were given a course of radiotherapy and were then randomly allocated to continued cyclical chemotherapy or not further chemotherapy until relapse. Non-responders to chemotherapy were treated with radiotherapy or palliatively. The median survival was 10.5 months in responders and 6 months in non-responders (P less than 0.01). The one-year survival in responders was 42%. There was no statistical difference in survival between patients treated with continued chemotherapy and those treated at relapse. Sixty-nine per cent of patients experienced no side effects from chemotherapy. Three indicators of non-response to chemotherapy were identified--exercise tolerance at diagnosis, macroscopic liver metastases, and inappropriate ADH secretion.

Adult↗

Circulating immune complexes in patients with cryptogenic fibrosing alveolitis.

Increased Clq binding levels have been obtained in serum from twenty-one (50%) of forty-two patients with cryptogenic fibrosing alveolitis (CFA) suggesting the presence of circulating immune complexes. There was a low frequency of positive results using a number of other tests for circulating immune complexes. The increased Clq binding levels were observed in six (35%) out of seventeen patients with lone lung involvement and in fifteen (60%) out of twenty-five patients with extrapulmonary connective tissue disorders. There was an especially close correlation between arthritis and elevated Clq binding. A strong correlation between Clq binding levels and levels of circulating rheumatoid factor (RF) and IgG, and enhancement in macrophage radiobioassay tests using RF-containing sera, suggested that RF might be involved in the circulating immune complexes in these patients. DNAase pre-treatment of sera did not influence the findings, and there was no correlation between Clq binding and levels of immunofluorescent ANA, C-reactive protein levels, or platelet counts. A weak correlation between Clq binding and erythrocyte sedimentation rates, and slightly lower binding levels in treated than untreated patients with 'lone' CFA suggested that binding levels may give some indication of disease activity and may in some instances be influenced by treatment.

Adult↗

The role of histocompatibility (HLA) antigens in asbestosis.

Histocompatibility antigens on the A, B and C loci have been studied in 172 asbestos workers, 92 of whom had radiographic evidence of asbestosis and 80 of whom had normal radiographs. Within each population, 77 were selected who matched for age, sex, duration from first exposure, duration of exposure and approximate heaviness of exposure. Results were also compared with 174 normal unexposed volunteers. No differences of statistical significance were found in the frequency of histocompatibility antigens tested when the matched or the total population of asbestos workers with and without asbestosis were compared. There was, however, a consistent trend of increase in B27 amongst those with asbestosis (11%) and this reached conventional significance (P < 0.05) when the 92 asbestotics were compared with the whole group having normal radiographs (asbestos workers 5.0% and volunteers 5.2%). Amongst the group having asbestosis, those with HLA-B27 had a significantly shorter exposure to the dust (13.5 years) compared with those without asbestosis (22.3 years), although the mean radiographic profusion score for the two categories was similar. No statistical differences could be found when B5, B8 and B12 were analysed in a similar way, but there was a trend suggesting that B5 was less frequent amongst a small group of cases showing radiographic progression over a three-year follow-up, compatible with the suggestion that this antigen might be linked with with some protective effect.

Asbestos↗

Lymphocyte responses to phytohaemagglutinin in patients with asbestosis and pleural mesothelioma.

Quantitative impairment of lymphocyte responses to phytohaemagglutinin (PHA) has been demonstrated in six (21%) out of twenty-eight patients with asbestos-associated pulmonary fibrosis, in comparison with a group of unexposed normal controls. The impairment tended to occur in patients with fairly severe fibrosis, comparatively short duration of exposure to asbestos dust and with increases in serum immunoglobulin levels. One patient with asbestosis and an associated bronchial carcinoma also had depressed lymphocyte responses to PHA. These findings suggest a relationship between defective T-lymphocyte function and the fibrotic response in asbestosis. Whether it is also linked with the development of lung cancer, occurring either before or at a pre-clinical stage of tumour growth, and is of value in identifying patients especially at risk should now be explored in longitudinal studies. However, eight out of ten patients with asbestos-associated pleural mesothelioma and without lung fibrosis showed no evidence of impaired cellular immunity, either by in vitro testing with PHA or by vivo delayed hypersensitivity skin testing, indicating that impaired T-lymphocyte function is unlikely to be a common finding in all types of asbestos-associated malignancy.

Adult↗

alpha 1-antitrypsin phenotypes in fibrosing alveolitis and rheumatoid arthritis.

alpha 1-antitrypsin (alpha 1-A.T.) phenotypes were determined in 55 patients with rheumatoid arthritis (R.A.), 33 patients with R.A. and either obstructive airways disease or recurrent chest infections, 49 patients with fibrosing alveolitis (F.A.), 22 patients with R.A. and F.A., and 200 healthy controls. A highly significant increase in the frequency of MZ phenotype was found among patients with F.A., both with and without R.A. Patients with R.A. alone had a normal distribution of phenotypes. Inherited modification of immune function may predispose to F.A. Alternatively, lowered levels of alpha 1-A.T. associated with non-M phenotypes may predispose to tissue damage with subsequent fibrosis.

Alleles↗