New leupeptin analogues: synthesis and inhibition data

Syntheses of several tripeptide analogues of leupeptin containing C-terminal argininal, lysinal, or ornithinal units are presented. The synthetic analogues were tested as inhibitors of trypsin, plasmin, and kallikrein. (Benzyloxycarbonyl)-L-leucyl-L-leucyl-L-argininal (2a) was significantly less effective as an inhibitor of trypsin and plasmin activity than leupeptin. (Benzyloxycarbonyl)-L-leucyl-L-leucyl-L-lysinal (2e) and (benzyloxycarbonyl)-L-leucyl-L-leucyl-L-ornithinal (2i) display different inhibition characteristics than (benzyloxycarbonyl)-L-leucyl-L-leucyl-L-argininal (2a). While (benzyloxycarbonyl)-L-leucyl-L-leucyl-L-argininal (2a) showed moderate inhibition of all three enzymes tested, (benzyloxycarbonyl)-L-leucyl-L-leucyl-L-lysinal (2e) was less effective as an inhibitor of trypsin and plasmin activity. Of the three enzymes tested, (benzyloxycarbonyl)-L-leucyl-L-leucyl-L-ornithinal (2i) showed significant inhibition of kallikrein activity only. Modifications made in the composition and sequence of the P2 and P3 amino acids also resulted in variations in the inhibitory activity of the analogues. In general, plasmin showed a strong preference for inhibitors which contain an L-phenylalanyl-L-leucyl or an L-leucyl-L-valyl unit in the P2 and P3 positions.     

Fluoroscopic peroperative cholangiography: technique and associated radiation hazards

The techniques specific to peroperative fluorocholangiography are discussed based on an experience of 632 cholangiograms and an estimation has been made of the associated radiation doses to staff and patients. Rapid and accurate information can be obtained during fluorocholangiography using appropriate techniques with acceptably low radiation hazards.     

The emerging role of induced hypothermia in the management of acute stroke.

Current treatment of acute stroke remains unsatisfactory. This review presents experimental and clinical data which suggest that mild induced hypothermia could be a potent and practicable neuroprotective treatment of acute ischaemic stroke and intracerebral haemorrhage. Hypothermia, if proven to be safe, effective and widely practicable in patients with acute stroke, could have an enormous positive impact on reducing the burden of stroke worldwide. Critical issues that will need to be considered in a well designed randomised controlled trial of induced hypothermia in acute stroke patients are discussed.     

Prediction of choledocholithiasis using a pocket microcomputer

A computerized method, using a small pocket computer, has been used to predict the presence of choledocholithiasis in a prospective series of 239 patients undergoing cholecystectomy. From an initial data base of 424 patients 36 factors were evaluated and the most important 2 of these were determined by multivariate analysis for use in the prospective analysis. Satisfactory operative cholangiograms were a prerequisite to evaluation of the statistical method and were obtained in 90.4 per cent of cases. Using the computerized method a common bile duct stone would have been overlooked in only 1 patient but 17 unnecessary explorations would have been carried out. The overall accuracy of the computerized method was 92.5 per cent. When the method was applied to a further study of 97 patients from a separate centre the overall accuracy was 85.6 per cent. If the method was used to aid selective use of operative cholangiography, cholangiograms would be performed in 20 per cent and stones would be overlooked in less than 1 per cent.     

Bone mineral content in patients with primary hyperparathyroidism: a comparison of conservative management with surgical treatment.

The management of patients with asymptomatic hyperparathyroidism remains controversial. This study examined the extent to which the presence of prospect of bone disease should influence treatment. Bone mineral content (BMC) of the distal forearm was measured by single photon absorptiometry in 67 patients with mild hyperparathyroidism. Twenty-six patients treated surgically and 17 managed conservatively were reviewed regularly for up to 4 years. Eighty per cent of patients had a baseline fat-corrected BMC within the local reference interval for age and sex, but about 75 per cent of values fell below the mean. BMC at the 'distal' site of the surgically treated patients improved or stabilized, but a continuing decline was seen in the patients managed conservatively (P less than 0.01). Differences were small and concern about future osteoporotic fracture should seldom be a major factor in making decisions about surgical correction of mild hyperparathyroidism.