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.     

Treatment of refractoriness to platelet transfusion by protein A column therapy

Ten thrombocytopenic patients (platelets < 10–24 × 10(9)/L) who were refractory to platelet transfusion were investigated for their responsiveness to staphylococcal protein A column therapy. Nine patients had previously been treated with steroids, intravenous immune globulin, and/or other forms of immunosuppressive therapy without improvement in their transfusion response. All patients were receiving multiple platelet transfusions without achieving 1-hour corrected count increments (CCIs) > or = 7500. Eight patients had antibodies that reacted with platelets and were directed against HLA class I antigens, ABO antigens, and/or platelet-specific alloantigens. Plasma (500-2000 mL) from each patient was passed over a protein A silica gel column and then returned to the patient. Patients received from 1 to 14 treatments. A positive response to protein A therapy was defined as at least a doubling of the pretreatment platelet count and/or two successive 10- to 120-minute posttransfusion CCIs > or = 7500. Following plasma treatments, 6 of 10 patients responded with daily platelet counts that averaged 48 +/− 11 × 10(9) per L as compared with counts of 16 +/− 7 × 10(9) per L (p < 0.0005) before treatment. Posttransfusion CCI values determined in four of these patients averaged 2480 +/− 810 and 10,010 +/− 3540 (p < 0.005) before and after treatment, respectively. In contrast, among the four unresponsive patients, platelet counts averaged 10 +/− 9 and 13 +/− 10 × 10(9) per L (p = NS), respectively, while posttransfusion CCIs were 700 +/− 1410 and 1520 +/− 2460 (p = NS), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Perforated colorectal neoplasms: correlation of clinical, contrast enema, and CT examinations

Results of clinical, contrast enema (CE), and computed tomographic (CT) examinations in 39 patients with perforated colorectal neoplasms were retrospectively reviewed. Twenty patients were toxemic at initial presentation, but in only four patients was the diagnosis of perforated colorectal neoplasm initially suspected clinically. CE study was performed in 22 patients and enabled the diagnosis of perforated neoplasm in 11 cases, neoplasm alone in eight, and neither neoplasm nor perforation in three. CT was performed in 38 patients and enabled the diagnosis of perforated neoplasm in 36; pericolic phlegmon but no mass lesion was evident in two. In 16 patients, CT also demonstrated metastatic disease. Because of its reliability in establishing the diagnosis and staging the extent of the inflammatory and neoplastic disease, CT is indicated in cases of suspected or proved perforated colorectal neoplasm and in cases in which CE study findings are indeterminate or suggestive of perforated neoplasm.