Enalapril, the ethyl ester of a potent angiotensin converting enzyme inhibitor, enalaprilat, was administered to healthy volunteers as a capsule containing 10 mg of the maleate salt, every 24h for eight doses. Serum profiles show little accumulation of enalaprilat following eight daily doses of enalapril maleate. An average effective half-life for accumulation of approximately 11h was calculated from urine data. Comparison of observed 24-h urinary recoveries of enalaprilat to predicted steady-state recovery indicates that an 'average' steady state for enalaprilat is attained by the third or fourth dose of enalapril maleate. Statistical comparison of daily urinary recoveries, as well as Cmin values for enalaprilat, confirm this. Observed fluctuations in serum and urine data during apparent steady state suggest some day-to-day variability in the absorption of enalapril maleate and/or its hydrolysis to enalaprilat. An accumulation ratio of 1.3 for enalaprilat was calculated from the predicted steady-state urinary recovery and observed urinary recovery for dose one.

in elderly patients, common bile duct stones often present atypically and co-existence with malignancy is not unusual; ampullary carcinoma has a relatively good prognosis and ERCP is a safe and effective procedure in the management of biliary obstruction.

Summary: Strep. pneumoniae was diagnosed as the cause of pneumonia in 40 (50%) of 80 consecutive adults admitted to St Stephen's Hospital with community-acquired pneumonia. None of the patients had evidence of Mycoplasma pneumoniae infection, and Legionella pneumophila serology was positive on only one occasion. In 29 patients (36%) no causative organism was demonstrated. The diagnosis of pneumococcal infection was obtained in 15 cases by isolating Strep. pneumoniae from the sputum, in 13 further cases by demonstrating pneumococcal capsular antigen in sputum, and in 12 other cases by detecting pneumococcal antigen in serum only. Only 2 cases with pneumococcal pneumonia were bacteraemic and 3 patients (7%), all aged more than 75 years, died. The relatively low bacteraemic and mortality rates suggest that community-acquired pneumococcal pneumonia currently seen in patients admitted to hospital in central London may not be so severe as in some other areas.

Eighteen patients who had developed a chylothorax during a 25 year period, 1955-80, were reviewed. The chylothoraces occurred as a complication of cardiothoracic surgery in 11 patients, of whom eight were children in the first decade of life. Five cases followed operations for coarctation of the aorta and two occurred as a complication of a Blalock shunt for Fallot's tetralogy. The chylothorax was evident within 48 hours of the operation in all but two patients. In seven cases a second operation was performed to prevent further chylous leakage and in two infants the thoracic duct was ligated. The remainder of the postsurgical chylothoraces responded to either continuous drainage or repeated aspiration and a low fat diet. There were no late sequelae of chylothorax following surgery. Spontaneous chylothorax was identified in seven patients and in five of these it was bilateral. Patients with spontaneous chylothorax were all adults and, despite treatment, had a poor prognosis. Three with malignant disease and two with pulmonary lymphangioleiomyomatosis had died within two years of the appearance of the chylothorax. Two patients with chronic idiopathic chylothoraces survived for more than two years and one of these developed a secondary fibrothorax.Chylothorax, the accumulation of thoracic duct lymph or "chyle" in the pleural space,' is a relatively uncommon condition and consequently few clinicians will have experience of more

In a double-blind controlled trial 14 chronic asthmatic patients with regular nocturnal exacerbations took 16 mg slow-release oral salbutamol (two Ventolin spandets), 450 mg slow-release aminophylline (two Phyllocontin Continus tablets), or placebo at midnight. Mean peak expiratory flow rates on waking were significantly higher on the active drugs than on placebo (p<001 for salbutamol; p < 005 for aminophylline) but neither drug abolished the overnight fall in PEFR. Plasma drug levels at 0600 hr were 17-3 ng/ml (+5 3 ng/ml SD) for salbutamol, and 7-1 ig/ml (±3 1 ig/ml SD) for theophylline. Steady-state data derived from plasma levels of salbutamol during intravenous infusion indicated that the morning salbutamol levels were probably in a therapeutic range for asthma. The morning theophylline levels, however, were suboptimal when aminophylline was given only at night.Early morning wheezing is a common symptom of asthma for which sustained release bronchodilator tablets are frequently prescribed. In normal people a diurnal variation of peak expiratory flow (PEFR) of up to 10% has been obs,erved.1 However, in asthma much larger variations frequently occur, and may sometimes pass unnoticed by the patient.2 These overnight falls in PEFR may continue apparently harmlessly foTr many years or may be associated with deterioration in the overall control of the subject's asthma.3 4Although slow-release bronchodi-lator preparations are widely prescribed to prevent nocturnal symptoms of asthma, there are few data to suggest the correct dose based on measurement of drug plasma levels. Information is available on the therapeutically effective range of plasma levels of theophylline for acute and chronic asthma, but there is no such information for salibuta,mol. This study was undertaken to investigate the plasma levels of salbutamol and theophylline produced by slow-release oral preparations, and to relate these to the degree of control achieved in chronic nocturnal asthma and