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Biomedical subjects

M Turner-Warwick

Publications and source records attributed to M Turner-Warwick.

At least 145 records · Page 8Linked to original sources

Immune reactions in pulmonary fibrosis.

Two groups of fibrosing lung disorders have been studied, namely connective tissue disorders and fibrogenic inorganic dust diseases. Antinuclear factors (ANA) are frequently raised in both, but to varying extents and having markedly different characteristics when analysed in detail. The evidence for immune complex deposition in the lung in human disease is summarized and the relationship between ANA and the radiographic extent of fibrogenic inorganic dust disease is described. The evidence of lymphocyte responsiveness is incomplete, but holds interesting potential. Preliminary studies of histocompatibility antigens are summarized and warrant further investigation.

Animals↗

A case of pulmonary veno-occlusive disease respondong to treatment with azathioprine.

Histological features of a lung biopsy specimen from a 46-year-old woman showed all the characteristics described in veno-occlusive disease. The clinical features, however, were distinctive in that in addition to the lung involvement there was alopecia, digital vasculitic ulcers, Raynaud's phenomenon, polyarthritis, and muscle weakness. Treatment with azathioprine resulted in a progressive improvement in her condition. It is suggested that pulmonary small vein occlusion may occur as a pattern of tissue response in more than one situation and that is sometimes more amenable to therapy than has been previously reported.

Alopecia↗

Studies in chronic allergic bronchopulmonary aspergillosis. 4. Comparison with a group of asthmatics.

A comparison is made of lung function tests and radiographic findings in 20 asthmatic patients with allergic bronchopulmonary aspergillosis paired in terms of sex, age, and duration of asthma with 20 other asthmatics in whom the diagnosis of aspergillosis was excluded in order to see if the aspergillosis causes more lung damage. One hundred per cent of the patients with aspergillosis and 75% of the patients with asthma alone showed a significantly reduced forced expiratory volume in one second (FEV1) before bronchodilator. All the patients in the two groups had a significantly reduced maximal expiratory flow at 50% vital capacity breathing air (V50air) but the severity of the reduction was statistically greater in the aspergillosis group. Reversibility in FEV1 of 15% and more was found in 50% of patients with asthma alone as against 31% of patients with aspergillosis. The degree of reversibility of FEV1 was also statistically greater in patients with asthma alone. Improvement of less than 20% of V50 after helium-oxygen breathing was found in 33% of the patients with asthma alone and in 75% of the patients with aspergillosis. Patients with aspergillosis also showed significantly (0-001 less than P less than 0-01) more reduced gas transfer factor. Radiological features of overinflation were as common in the two groups. Tubular and ring shadows were found in 95% and 60% respectively of patients with aspergillosis as against 45% and 15% of patients with asthma alone.

Adult↗

Progressive airway obliteration in adults and its association with rheumatoid disease.

Six patients with rapidly progressive airway obliteration in the absence of chronic bronchitis or emphysema are reported. Because this pattern of lung disease is very uncommon and five of the six patients had classical rheumatoid arthritis an association between the two diseases is suggested. The patients presented with rapidly developing breathlessness, and râles and a high-pitched mid-inspiratory squeak were heard over the lung fields. Chest radiographs showed distended lungs but were otherwise normal. Tests of lung fuction showed airflow obstruction, most marked at low lung volumes, with air trapping. The carbon monoxide gas transfer coefficient, maximum static recoil pressure and static compliance were normal. In spite of treatment with antibiotics, bronchodilators and corticosteroids, five died in respiratory failure five to 18 months after first becoming breathless. Post-mortem examination in four patients showed an obliterative bronchiolitis but no mucous gland hypertrophy or significant emphysema.

Adult↗

Autoantibodies in patients with chronic bronchitis.

Antinuclear antibody (ANA) was found in low titre in 28% of a group of 50 patients with chronic bronchitis by MRC criteria and defined as "severe", that is having at least six infective episodes a year, a vital capacity of less than 70% of predicted and less than 30% reversibility of their airways obstruction after inhalation of isoprenaline. By contrast ANA was found in only 4% of age and sex matched non-bronchitic controls and in none of 28 patients with "less severe" chronic bronchitis in whom these three criteria of severity were not fulfilled. The presence of antinuclear antibody was unrelated to the duration of the disease, sputum volume or the presence of purulent sputum at the time of the study. Neither was it related to blood eosinophilia, respiratory function, smoking or the presence of bacterial precipitins in the patient's serum. These findings are important because they suggest that incidental chronic bronchitis, unless it is extremely severe, is unlikely to contribute substantially to the prevalence of antinuclear antibody found in certain other lung diseases. There was no significant increase in smooth muscle or "reticulin" antibodies in this series of patients.

Age Factors↗

Cryptogenic pulmonary eosinophilia.

The clinical and immunological features of fifteen cases of cryptogenic pulmonary eosinophilia are reported. There were ten women (mean age 35.4 years) and five men (mean age 42 years). Eight gave a previous history of asthma and seven had none. Thirteen of the fifteen patients had negative skin test to common allergens. Many features of a systemic illness were present in the asthmatic and non-asthmatic groups including anaemia, weight loss, fever and a grossly raised ESR. An absolute polymorphonuclear leucocytosis was frequent as well as the obligatory increase in blood eosinophils used as one of our criteria for inclusion. Hepatomegaly (three cases), splenomegaly (four cases) and hilar node enlargement (one case) were seen in the group without asthma. Evidence of renal involvement or necrotizing vasculitis was notably absent and the response to small doses of corticosteroids was dramatic. Immunologically the striking feature was a disproportionate increase in blood eosinophils compared with only minor elevations in the total serum IgE levels. This stands in contrast to patients with bronchopulmonary aspergillosis and helminth infestation. Studies of cytophilic antibodies using histamine liberation after challenge with antibodies to immunoglobulin sub-classes in six patients showed a marked increase in IgG2 and lesser increases of IgE and IgG3. No evidence of antibodies specific to A. fumigatus was found. The amount of cytophilic antibody was also in contrast to that found in bronchopulmonary aspergillosis.

Adolescent↗

Lymphocyte sensitization to Aspergillus fumigatus antigens in pulmonary diseases in man.

In vitro studies of T-lymphocyte responses using five different batches of Aspergillus fumigatus antigens, were undertaken in twelve patients with A. fumigatus related lung disease and in three normal controls. Using a leucocyte migration method, five of the twelve patients showed significant inhibition of leucocyte migration with a migration index of 0-80 or less to A. fumigatus, but in only three was this demonstrated with more than one batch of antigen (one patient with aspergilloma and two with bronchopulmonary aspergillosis). The same antigens were used in lymphocyte transformation tests. Only two patients, one with aspergilloma and one with bronchopulmonary aspergillosis, showed clearly significant transformation although there were several borderline results. Only three patients had evidence of delayed skin responses to A. fumigatus antigens in vivo, one with aspergilloma, one with bronchopulmonary aspergillosis and one with atypical bronchopulmonary aspergillosis. Two of these three patients also had one or more positive in vitro test results. Thus T-lymphocyte sensitization to A. fumigatus as demonstrated by these in vitro methods, although present in occasional patients, was not clearly related to any one particular clinical syndrome in this small group of patients with aspergillus related pulmonary disease. There was, however, one of the three aspergilloma patients with positive lymphocyte transformation to all five batches of antigens and having higher transformation indices than in any other patient. This suggest that lymphocyte studies should be extended in this group. In contrast to the frequent negative results using A. fumigatus antigens, evidence of T-lymphocyte sensitization to either Candida albicans or Mycobacterium tuberculosis or both, was shown by positive delayed hypersensitivity skin responses and in vitro inhibition of leucocyte migration in the majority of the patients, despite which lymphocyte transformation was often negative. The possibility of impaired capacity to transform is supported by the finding of an impaired response to phytohaemagglutinin (PHA) in four of the twelve cases. This information, together with other data discussed, helps to complete the contrasting immunological profiles seen in different Aspergillus fumigatus related lung diseases.

Antigen-Antibody Reactions↗

High prevalence of antinuclear antibodies in sandblasters' silicosis.

Of 39 silicotic sandblasters evaluated in 1972 and 1973, 17 (44 per cent) had positive serum antinuclear antibody reactions. This prevalence is higher than those reported for other pneumonconioses. Comparison of the groups positive and negative for antinuclear antibodies showed that patients positive for antinuclear antibodies were unlikely to have normal ventilatory function and were more likely to have roentgenograms showing large opacities. Both groups had similar proportions showing lobar cavitation or contraction.

Antibodies, Antinuclear↗

Respiratory involvement in systemic lupus erythematosus. A clinical and immunological study.

Thirty patients fulfilling conventional criteria for systemic lupus erythematosus and who presented with extensive pleural and pulmonary involvement were studied retrospectively. Four overlapping patterns of respiratory disease were identified and observations were made on their clinical presentation, radiographic abnormalities and response to treatment. A low incidence of severe renal disease was found in this series of patients and this was in keeping with the general finding of low serum binding using native DNA in a globulin Farr-binding technique (greater than 20% binding in only 4/21 (19%) of the series) and normal or elevated serum complement (C3) levels. Precipitating antibody detected by double diffusion and counter-current immunoelectrophoresis and probably reacting in most cases with single-stranded DNA was, however, detected in 66% of pretreatment serum samples tested. This evidence supports the idea that different types of anti-nuclear antibody may be associated with different clinical manifestations seen within a group of patients who broadly fulfil the criteria for SLE.

Adolescent↗

Cytophilic antibodies in bronchopulmonary aspergilloma and cryptogenic pulmonary eosinophilia.

The immunoglobulin class and subclass of cytophilic antibodies have been studied using peripheral leucocytes from twenty-two patients with allergic bronchopulmonary aspergillosis, aspergilloma and cryptogenic pulmonary eosinophilia. In patients with allergic bronchopulmonary aspergillosis, significantly increased histamine liberation occurred following challenge of their leucocytes with antisera to IgE, IgG2, IgG3 and IgG4 as well as with Aspergillus fumigatus antigen. The results were considerably modified if the patient was receiving corticosteroids at the time of the test. The presence of IgG2-specific antibody to A. fumigatus in the serum of one patient, capable of sensitizing donor leucocytes, was demonstrated in passive sensitization experiments. In two patients with uncomplicated aspergillomas no evidence of cytophilic antibody to any class was found although large amounts of precipitating IgG antibody was present in the serum. Two patients with aspergilloma and systemic symptoms of weight loss and fatigue (which have been interpreted by others as 'hypersensitivity' responses) had increased amounts of cytophilic antibody similar to those with allergic bronchopulmonary aspergillosis. Six patients with cryptogenic pulmonary eosinophilia were also studied. No evidence of specific antibody to A. fumigatus was found but, as a group, significantly increased histamine liberation using antisera to IgG2 was demonstrated. Individual patients also showed evidence of other classes of cytophilic antibody, one having IgE, three IgG3 and two IgG4. The relationship between heat-stable short-term sensitizing antibody (IgG STS) inducing immediate skin responses and the pattern of cytophilic antibodies found in our patients with bronchopulmonary aspergillosis having dual (immediate and late reactions) is discussed. Clinically these tests are of diagnostic value and they may be helpful in assessing symptomatic patients with aspergillomas for corticosteroid treatment.

Adult↗

The HL-A system in asbestos workers.

In a study of the HL-A system in 56 selected asbestos workers referred to the Pneumoconiosis Medical Panel with definite or suspected asbestosis, the W 27 antigen was found more often than among a control population. Six of the 10 asbestos workers with the W 27 antigen had definite radiographic evidence of asbestosis compared to 13 out of 46 without the W 27 antigen. These observations, if confirmed, suggest that the W 27 antigen may provide a useful marker of an enhanced susceptibility to the tissue-damaging effects of asbestos dust.

Adult↗

Diagnosis and management of alveolar proteinosis: the rôle of electron microscopy.

The diagnosis and management of three cases of pulmonary alveolar proteinosis are described. The electron microscopic appearances of lung biopsy material, lung washings, and sputum and the value of this method of sputum examination in extremely ill patients are demonstrated. The practical details of controlled volume bronchial lavage are described and the good clinical and physiological response of patients reported. The findings have been compared with those of experimental pulmonary alveolar proteinosis, and the pathogenesis of the condition is discussed.

Adult↗

Autoantibodies in patients with bronchial carcinoma.

No overall increase in the incidence of antinuclear, smooth muscle or reticulin antibodies was observed in a group of 105 patients with bronchial carcinoma of various classified histological types. Smooth muscle antibody was, however, demonstrated in 27% of patients with undifferentiated carcinoma compared to 5% of controls (P less than 0-05). A highly significant increase in antinuclear antibodies in patients with adenocarcinoma was found (31% compared with 5% of controls--P less than 0-01). There as no apparent correlation between the presence of these antibodies and age, sex or other clinical features studied. A detailed study of the reproducibility of the antibody results, studied by indirect immunofluorescence in patients with bronchial carcinoma, is reported.

Adenocarcinoma↗

Nocturnal and morning asthma. Relationship to plasma corticosteroids and response to cortisol infusion.

Nocturnal and early morning breathlessness is a common and important symptom in asthmatic patients. Six patients in whom these symptoms were a major clinical problem have been studied by serial measurements of peak expiratory flow rate (PEFR) and plasma corticosteroids over two 24-hour periods. Although PEFR and plasma corticosteroids are lowest during the night or early morning, preventing the nocturnal fall in plasma corticosteroids by cortisol infusion did not prevent the fall in PEFR in five out of the six patients. The circadian rhythm of corticosteroid secretion does not appear to be the main cause of nocturnal and early morning asthma.

Adrenal Cortex Hormones↗