Prolonged binding of radiolabeled recombinant tissue-type plasminogen activator after angioplasty and enclosed thrombolysis of the femoropopliteal arteries.

The authors measured the binding of indium-111-labeled recombinant tissue-type plasminogen activator (rt-PA) within the recanalized femoropopliteal segment after percutaneous transluminal angioplasty (PTA) and enclosed thrombolysis. In patients with long occlusions (n = 3), 91 micrograms of rt-PA was bound 1 hour after the procedure, and the half-time of the final washout curve averaged 114 hours. After PTA in patients with multiple stenoses (n = 6), 45 micrograms of rt-PA was bound, and the half-time averaged 32 hours. These values were significantly smaller than those in patients with occlusions (P < .01). In patients with a single stenosis (n = 4), 19 micrograms of rt-PA was bound, and the half-time averaged 5 hours. These values were significantly smaller than those in patients with multiple stenoses (P < .01). The progressive accumulation of rt-PA at the sites of PTA therapy is most likely related to increasing presence of fibrin with increasing lesion severity. Fibrin accumulation may be partly responsible for early failures after PTA in extensive lesions. Removal of this fibrin with enclosed thrombolysis might improve patency.

Detection of deep venous thrombosis with indium 111-labelled monoclonal antibody against tissue plasminogen activator.

The administration of a radiolabelled monoclonal antibody against tissue plasminogen activator allows detection of areas with increased fibrinolytic activity, i.e. those with an active thrombotic lesion. Eight patients with phlebographically verified deep venous thrombosis were examined. At the time of immunoscintigraphy study they were examined receiving anticoagulant therapy. Some 75-85 MBq indium 111-labelled antibody were injected, and scintigrams were obtained after 30 min and after 24 h. The precise site of the thrombus could not be visualized after 30 min due to high background activity, whereas after 24 h it was detectable in all patients. The thrombus/background ratios achieved are twice as high as those observed in a human antifibrin antibody study. These preliminary data suggest a high sensitivity of our t-PA-specific antibody for the detection of active deep venous thrombosis in man, and our antibody seems to offer theoretical advantages over both platelet and fibrin-specific antibodies.

The therapeutic effect of methyl-salazosulphapyridine versus salazosulphapyridine in active ulcerative colitis. A double-blind controlled trial.

In an attempt to improve the ratio between therapeutic effect and side effects of salazosulphapyridine (SASP), methyl-salazosulphapyridine (methyl-SASP) was compared with SASP in a randomized controlled double-blind trial, without cross-over, in patients with active ulcerative colitis. The patient group comprised 53 patients. The daily doses were 1 g SASP x 3 and 125 mg methyl-SASP x 3. The methyl-SASP group comprised 26 patients, the SASP group 27 patients. The treatment period was 4 weeks. Applying clinical symptoms (bowel movements, registered by the patients on special charts), clinical condition (assessed by the patient), proctoscopic signs, and registration of side effects, it is concluded that methyl-SASP had an effect on ulcerative colitis indistinguishable from that of SASP. The rate of side effects was significantly less in the methyl-SASP group. The blood concentrations of SASP, methyl-SASP, sulphapyridine, and methyl-sulphapyridine were estimated at start during, and at the end of the trial. The methyl-SASP concentration was on an average twice as high as that of SASP, and the methyl-sulphapyridine on an average 1/13 of sulphapyridine, the differences being significant. It is concluded that methyl-SASP presents an improvement in the effect/side effect ratio when dealing with symptomatic ulcerative colitis. The discrepancy between the outcome of the present trial and the lack of effect in a controlled trial on the relapse-preventing effect of methyl-SASP is at present unexplained. A type II error in the present trial (or a type I error in the prophylactic one) is a possibility, or the patient-group selected for the present trial had a spontaneously benign course, cases demanding prednisone or colectomy having been excluded.

The relapse-preventing effect of methyl-salazosulphapyridine compared to salazosulphapyridine during long-term treatment of ulcerative colitis. A double-blind controlled trial.

In an attempt to improve the relapse-preventing effect of salazosulphapyridine (SASP) and to encircle the part of the molecule essential for therapeutic actin, methyl-SASP was compared to SASP in a controlled double-blind trial without cross-over. The patient group comprised 33 patients with ulcerative colitis who had been symptom-free for 1--6 months on continuous treatment with SASP (on an average 2 g daily). The daily doses were SASP 1 g X 3 and methyl-SASP 125 mg x 3. Thirty patients completed the trial, 14 on SASP and 16 on methyl-SASP. Applying clinical criteria, the relapse rate after 6 months was 0.14 in the SASP group and 0.69 in the methyl-SASP group. The difference is highly significant. The blood concentrations of SASP, methyl-SASP, sulphapyridine (SP), and methyl-sulphapyridine (methyl-SP) were measured after 3 and 6 months. The methyl-SASP concentration was on an average twice as high as that of SASP, and the methyl-SP on an average 1/10 of SP (the differences are significant). It is concluded that whereas SASP showed a relapse-preventing effect in ulcerative colitis in this study comparable to that previously reported, the effect of methyl-SASP was only comparable to that of placebo, and the active substance in SASP does not seem to be unsplit SASP.