Inhibition of the platelet glycoprotein (GP) IIb/IIIa receptor with the murine monoclonal antibody 7E3 abolishes ex vivo platelet aggregation, reduces thrombogenicity, and sustains arterial recanalization with recombinant tissue-type plasminogen activator (rt-PA). A chimeric murine/human Fab fragment of 7E3 (c7E3-Fab) has a markedly reduced immunogenicity, but its potency as an adjunct for thrombolysis with rt-PA has not been evaluated. The effects of a single intravenous bolus injection of aspirin (17 mg/kg) or c7E3-Fab (0.45 mg/kg) on thrombolysis and reocclusion induced with rt-PA were studied in groups of six baboons with femoral arterial thrombosis and superimposed high-grade stenosis. This dose of c7E3-Fab blocked 96 +/- 1% of the platelet GPIIb/IIIa receptors and abolished ADP-induced platelet aggregation. Bolus intravenous injections of rt-PA (0.25 mg/kg) were repeated at 15-minute intervals until reperfusion occurred (maximum of four injections). In the aspirin group, reperfusion was obtained within 51 +/- 16 minutes (mean +/- SD) but was rapidly followed by reocclusion within 6 +/- 9 minutes and by cyclic reflow and reocclusion. In the c7E3-Fab group, reperfusion was obtained within 25 +/- 8 minutes (P < .01 versus aspirin group) and was associated with a delayed reocclusion of 63 +/- 63 minutes (P < .05 versus aspirin group). Template bleeding times remained unchanged in the aspirin/rt-PA group but were markedly prolonged (to > 30 minutes) in the c7E3-Fab/rt-PA group.(ABSTRACT TRUNCATED AT 250 WORDS)
Probucol administration of 4 weeks produced torsades de pointes associated with exacerbated QTinterval prolongation in a 36-year-old womanwith Romano-Wardsyndrome. With discontinuance of probucol, the QTinterval corrected for rate shortened from 620 msec to 500 msec and ventricular ectopic beats disappeared completely. Although probucol is known to prolong the QTinterval, associated ventricular tachyarrhythmia has not been reported in humansas yet. This case suggests that one should be very careful in the administration of probucol to patients with long baseline QT intervals.
Objective The purpose of this study is to investigate the physical changes of the lower leg muscles in the compartment by observing the changes in the shear wave velocity of the gastrocnemius, soleus and tibialis anterior muscles with time in the sitting position for 2 hours and after elevation of the lower leg. Materials and methods The subjects were 24 healthy adult males (average age 26.6 years). Shear wave velocity was measured by Aplio 500 in immobilized leg immediately after the start of sitting, 60 minutes and 120 minutes after the start of sitting. After 120 minutes the subjects raised the lower leg for 3 minutes, then measured again. Results In the lateral and medial gastrocnemius, there was a significant increase in the velocity at 60 (1.58 ± 0.06, 1.70 ± 0.09 m/s) and 120 minutes (1.70 ± 0.10, 1.83 ± 0.11 m/s) after the start of the test (1.52 ± 0.06, 1.66 ± 0.10 m/s), respectively (p<0.01). In the soleus and the tibialis anterior, there was a significant increase in the velocity at 120 minutes (1.89 ± 0.17, 2.30 ± 0.24 m/s) compared to after the start (1.60 ± 0.15, 2.15 ± 0.26 m/s), respectively (p<0.01). In all muscles, there was a significant decrease in the velocity after the raising compared to that of 120 minutes (p<0.01). Conclusions It has been reported that the change of shear wave velocity with time is proportional to the intramuscular pressure in the leg compartment, and it is assumed that the increase of shear wave velocity in the 2-hour seated leg is due to fluid retention in extra-cellular space of the compartment.
Arg-Gly-Asp-containing pentapeptide, has a high affinity (dissociation constant of 4 nM) for the platelet glycoprotein (GP) Ilb/IIIa receptor. The effects of its intravenous or endobronchial administration on thrombolysis, reocclusion, and bleeding time prolongation induced with 0.45 mg/kg bolus injections of recombinant tissue-type plasminogen activator in combination with intravenous heparin (4,000-unit bolus and 1,000 units each hour) were studied in a canine model consisting of an erythrocyte-rich blood clot in the left anterior descending coronary artery. Coronary patency was monitored for 3 hours both by ultrasonic flow probe and by repeat coronary angiography. Four groups of six to 10 dogs were studied with intravenous infusions of 0, 0.1, 0.2, or 0.3 mg/kg G4120 over 60 minutes. G4120 at a dose of 0.3 mg/kg reduced the time to reflow from a mean control value of 45 to 8 minutes (p=0.036) and delayed reocclusion (p=0.001). Four groups of five or six dogs were studied with endobronchial instillation of G4120 in a randomized, blinded study design using 0,0.13,0.25, or 0.5 mg/kg G4120. Endobronchial G4120 at a dose of 0.5 mg/kg reduced the time to reflow from a mean control value of 52 to 7 minutes (p=0.039) and abolished cyclic reocclusion and reflow (p=0.008). G4120 induced a dose-related transient prolongation of the template bleeding time and inhibition of ADP-induced platelet aggregation. G4120, a synthetic low-molecular-weight GPIIb/IIIa inhibitor that may be produced by chemical synthesis, may be of clinical value as a conjunctive agent for thrombolysis in patients with ischemic coronary syndromes. (Arteriosclerosis and Thrombosis 1993;13:738-747) KEY WORDS • acute myocardial infarction • thrombolytic therapy • arterial reocclusion • template bleeding time • glycoprotein Ilb/IIIa receptor I t is well established that thrombolytic therapy improves the outcome of acute myocardial infarction and that the conjunctive use of anticoagulants and /or antiplatelet agents increases the efficacy of coronary arterial thrombolysis. 12 The efficacy of heparin and aspirin in enhancing and sustaining coronary arterial recanalization in humans is, however, limited,
Introduction: Prolonged sitting causes leg discomfort. We evaluated shear wave velocity (SWV) of leg muscles, leg circumference, and leg discomfort associated with 2 h sitting. Methods: Twenty-one middle-aged men and 19 middle-aged women participated in the study. SWV and leg circumference was measured just after sitting, 60 min, 120 min, and after 3 min of leg raising. Leg discomfort was assessed before sitting and 120 min. Results: SWV was significantly greater in men than women and increased over time, and decreased with leg raising. The percentage increase in lower leg circumference was significantly greater in women than in men, and it increased over time. Leg discomfort significantly increased after 120 min in both men and women. Discussions: Because SWV is proportional to an increase in intramuscular compartment pressure in the lower leg, intramuscular compartment pressure increased over time with sitting and decreased with leg raising. Considering the changes in SWV and leg circumference, it was inferred that prolonged sitting causes an increase in intramuscular compartment pressure and intravascular blood volume, as well as an increase in water content in the leg subcutaneous tissue. Leg discomfort was estimated to be due to increased intra-leg fluid. Brief leg raising may resolve leg edema and discomfort.
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