To determine whether asthma alone can cause irreversible airflow obstruction 42 men and 47 women with chronic asthma (mean duration 22 (SD 13) years) without evidence of other disease likely to cause irreversible airflow obstruction were treated with theophylline orally and a beta agonist both orally and by inhalation for four weeks. After two weeks of treatment the FEV, was less than 85% of the predicted normal value (%P) in 48 patients and these individuals then received prednisolone 0*6 mg/kg/day for two weeks. Duration and severity of asthma and smoking history were quantified by questionnaire; 38 patients were current smokers or ex-smokers. FEV1 was measured at 0, 2, and 4 weeks. The mean difference between the best FEV1 during the study and the predicted normal value was 0-29 1 (p < 0.001); FEVy %P decreased with age (r = -030, p < 0.01) and with the duration (r = -0 47, p < 0.001) and severity (r = -0*55, p < 0.001) of asthma. Similar findings were noted when the results for non-smokers and those whose asthma started in adult life were analysed separately. We conclude that asthma alone can cause irreversible airflow obstruction and that the degree of obstruction is a function of the duration and severity of previous asthma. The results suggest the possibility that irreversible airflow obstruction in asthma may be preventable by minimising the degree of persistent asthma.
1591Clostridium tetani, however, have been found in up to 40%/o of samples of human faeces.' Another of our patients developed postoperative tetanus, which was attributed to self-contamination, after removal of a tumour of the buttock. Since rubber-band ligation of haemorrhoids produces an avascular area, and since this is in contact with a potential source of Cl tetani, the tetanus in this case may reasonably be attributed the operation. Certainly the time relationship fits in with the incubation period of tetanus. Case reportsA 76-year-old man developed pruritus after four years' continuous treatment with practolol 300 mg daily for angina of effort. He had an eczematous rash with palmar erythema; dryness of the eyes was confirmed by Schirmer filter paper testing. Smooth, non-tender hepatomegaly was noted. The following measurements were made: serum bilirubin 25 ,tmol/l (1.5 mg/100 ml) (normal 1-7-17,tmol/l (0.1-1.0 mg/100 ml)), alkaline phosphatase (liver isoenzyme) 405 IU/l (normal 20-90), serum aspartate transaminase (SGOT) 12 IU/I (normal 4-20), serum albumin 36 g/l, serum total globulin 40 g/l, serum IgM 2 2 g/l (0-7-2 0), IgG 11-6 g/l (9-5-16 5). Hepatitis B antigen was absent. Antinuclear factor was present (titre 1/80) as was smooth muscle antibody (1/20) and mitochondrial antibody (1/80). Liver scan and histological examination of a needle biopsy specimen confirmed the presence of cirrhosis.He remained well after practolol was stopped, but liver function tests showed persisting cholestasis. The development of cervical lymphadenopathy two years later, however, led to the diagnosis of nodular sclerosing Hodgkin's lymphoma. Despite radiotherapy he died after six months. Patent bile ducts were found at necropsy, and histology of tissue obtained a few minutes after death confirmed advanced cirrhosis with proliferating bile ducts and lymphocyte aggregates consistent with primary biliary cirrhosis. Staining with orcein and rubeanic acid showed hepatocytic metalloprotein complex as found in PBC.3 Typical sclerosing peritonitis affecting the jejunum was also present.A 57-year-old man was treated with practolol 300 mg/day for angina. After seven months he developed a psoriasiform rash and two months later he complained of dryness of the eyes. Liver function was not tested until 16 months after discontinuing the drug. Findings were: serum bilirubin concentration 50 ,imol/l (3 0 mg/100 ml), alkaline phosphatase concentration 144 IU/l, and SGOT 15 IU/I. Serum protein and immunoglobulins were normal as were autoantibody tests except mitochondrial antibody, which was positive to a titre of 1/160. A needle biopsy specimen of the liver showed normal lobular architecture, but near bile ducts were large epithelioid granulomata with surrounding lymphocytes (fig calculate the probability of men with PBC being exposed to practolol. By making several assumptions, an estimate of the figure may be obtained from the number of prescriptions for practolol and the number of certified deaths from PBC a year. Two cases of PBC expos...
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