Infusion Subject

The implication of these functionai studies is that shifts in receptor occupancy by allergen-specific IgE could restore basophil mediator reiease. Further support for this hypothesis was obtained from iater portions of the same phase I E25 trial. After 28 weeks of biweekly infusions, subjects were randomized to receive a 3 to 20-fold reduction in E25 dosing and continued for another 18 weeks. The result of this reduction was an increase reflected in free serum IgE levels from a mean of 7 ng/mL at week 28 to approximately 21 ng/mL at the termination of infusions (68). By the end of this treatment period, the ievels of basophii surface IgE expression and FceRIa rose three- to fourfoid, with the average number of receptors per basophil rising to nearly 35,000 per cell at the... 

In normal human subjects, ANP infusion for one hour causes increased absolute and fractional sodium excretion, urine flow, GFR, and water clearance (53—55). As shown in many in vitro and in vivo animal studies, ANP achieves this by direct effect on the sodium reabsorption in the inner medullary collecting duct, ie, by reducing vasopressin-dependent free-water and sodium reabsorption leading to diuresis and by indirect effect through increased hemodynamic force upon the kidney. ANP inhibits the release of renin and aldosterone resulting in the decreased plasma renin activity and aldosterone concentration (56,57). 

A reversed bridging approach has been proposed by Keris et al. In this study, 12 patients (three ICA occlusions and nine MCA occlusions) out of the 45 enrolled (all with an NIHSS score >20) were randomized to receive an initial lA infusion of 25 mg of rt-PA over 5-10 minutes, followed by IV infusion of another 25 mg over 60 minutes, within 6 hours of stroke onset (total combined dose 50 mg with a maximum dose of 0.7 mg/kg). The remaining 33 patients were assigned to a control group and did not undergo any thrombolysis. TIMI 2 and 3 recanalization occurred in 1 of 12 and 5 of 12 of the patients, respectively. There were no symptomatic ICHs. At 12 months, 83% of the patients in the thrombolysis group were functionally independent, whereas only 33% of the control subjects had a good outcome. 

The Interventional Management of Stroke (IMS I) Study was a multicenter, open-labeled, single-arm pilot study in which 80 patients (median NIHSS 18) were enrolled to receive IV rt-PA (0.6 mg/kg, 60 mg maximum, 15% of the dose as a bolus with the remainder administered over 30 minutes) within 3 hours of stroke onset (median time to initiation 140 minutes). " Additional rt-PA was subsequently administered via a microcatheter at the site of the thrombus in 62 of the 80 patients, up to a total dose of 22 mg over 2 hours of infusion or until complete recanalization. Primary comparisons were with similar subsets of the placebo and rt-PA-treated subjects from the NINDS rt-PA Stroke Trial. The 3-month mortality in IMS I subjects (16%) was numerically lower but not statistically different than the mortality of the placebo (24%) or rt-PA-treated subjects (21%) in the NINDS rt-PA Stroke Trial. The rate of symptomatic ICH (6.3%) in IMS I subjects was similar to that of the rt-PA-treated subjects (6.6%) but higher than the rate in the... 

In a mechanistic study of renovascular response to angiotensin II infusion, Hopkins et al. showed that the expected decrease in renal blood flow after a mild pressor dose of angiotensin II was least in TT subjects [52]. Thus, the M235T angiotensinogen gene polymorphism was associated with a blunted renovascular response. 

The product displays a mean serum half-life of 18.8 h in humans. It has been evaluated in four clinical trials involving a total of 128 subjects and in the context of both spontaneous bleeding and surgery. Some 88 per cent of the total infusions administered for bleeding were rated as providing a good or excellent response. Reported side effects, although uncommon, included hypersensitivity, as well as headache, fever and nausea. BeneFix is marketed by Wyeth. 

As shown in double-blind, placebo-controlled, randomized studies with healthy subjects, both infused [145] and oral [146] L-arg significantly inhibited (by =40%) ADP-induced platelet aggregation in vitro and potentiated platelet cGMP content. The effect, though, was weak the plasma concentration of L-arg required to produce an anti-platelet effect was some 2-fold above normal, steady-state levels, and the oral anti-aggregatory L-arg dose was 4-fold greater than the usual daily L-arg intake in humans. The infused L-arg dose that effectively inhibited platelet activity (30 g total) was hypotensive and increased heart rate, whereas the oral anti-platelet dose (7 g per day over 3 days) did not affect blood pressure, suggestive of oral L-arg platelet selectivity. 

A comprehensive, randomized, placebo-controlled trial of infused bolus L-arg and its enantiomer (D-arg) included healthy subjects, non-insulin dependent diabetics, hypertensive subjects, and normotensives with primary hypercholesterolemia [147]. A blood-pressure drop and an acute inhibition of ADP-induced aggregation in platelet-rich plasma were observed in all subjects after L-arg administration (<5 g). Both responses to L-arg infusion closely correlated in magnitude, were weaker in noninsulin dependent diabetics and hypercholesterolemics, and declined with increasing age. Notably, D-arg did not elicit any of the L-arg effects, which were reduced by some 70% when superimposed upon ongoing, nonselective NOS inhibition with infused L-N-monomethyl-arginine (L-NMMA). Since D-arg is not a NOS substrate, and L-NMMA is a substrate-competitive NOS inhibitor, the L-arg effects observed in this study were theorized to reflect a rise in vascular NO production by eNOS. In contrast, the inhibition of platelet aggregation observed in vitro after a 5 min L-arg infusion (160 mg total dose) into healthy subjects and patients with angiographic... 

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