ABSTRACT
OBJECTIVES: The evaluation of success and complication rates of ultra high-dose recombinant tissue plasminogen activator (rt-PA) administered over a short time frame in the treatment of acute lower limb ischemia. METHODS: This was a prospective single-center study. The outcome of treatment in 97 patients with acute limb ischemia (<14 days) with the use of catheter directed rt-PA infusion was evaluated. The mean total dose of rt-PA was 54.1 mg (50-60 mg) and was administered for a mean of 2.51 hours (2-4 hours). Thrombolytic success was defined as 95% thrombolysis of an occluded segment with return of antegrade flow. Thirty-day complication and amputation-free survival rates were calculated. RESULTS: Thrombolytic success was achieved in 83.5%. Overall clinical success was 88.7%. The 30-day amputation-free survival rate was 93.8%. Major bleeding complications occurred in 10 patients (10.3%). There were two deaths (2.1%) and four amputations (4.1%). Long-term amputation-free survival was 70%. CONCLUSIONS: Administration of ultra-high doses of rt-PA over a short time period gives promising results. Such delivery improves patient tolerance by rapid restoration of limb perfusion; however further studies are required to confirm these results.
Subject(s)
Fibrinolytic Agents/adverse effects , Ischemia/drug therapy , Leg/blood supply , Thrombolytic Therapy/methods , Tissue Plasminogen Activator/administration & dosage , Acute Disease , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Prospective Studies , Recombinant Proteins/administration & dosage , Recombinant Proteins/adverse effects , Time Factors , Tissue Plasminogen Activator/adverse effectsABSTRACT
The ;malic' enzyme (EC 1.1.1.40) has been purified (300-fold) from wheat germ and its abilities to catalyse the decarboxylation and the hydrogenation of oxaloacetic acid and oxaloacetate esters was studied. The free 1-carboxyl group is essential for the interaction of oxaloacetates and substituted oxaloacetates with the enzyme via cations. The free 4-carboxyl group is required for the decarboxylation but is not indispensable for the hydrogenation. At high concentrations, cations inhibit the enzymic hydrogenation of oxaloacetic acid but not that of 4-ethyl oxaloacetate. A plausible inhibitory mechanism is proposed.
