Quantification of abciximab-induced platelet inhibition is assay dependent: a comparative study in patients undergoing percutaneous coronary intervention.

BACKGROUND: The best method for measuring the degree of platelet inhibition with glycoprotein (GP) IIb-IIIa antagonists during percutaneous coronary intervention (PCI) and the optimal degree of periprocedural inhibition is uncertain. Low molecular weight heparins have been reported to cause less platelet activation than unfractionated heparin. Therefore, compared with unfractionated heparin (UHF), a low molecular weight heparin could enhance measured platelet inhibition. In this study, we compared 3 methods of measuring platelet inhibition and investigated the effects of half doses of abciximab in combination with either UFH or the low molecular weight heparin dalteparin in patients undergoing PCI with planned abciximab administration. METHODS: Abciximab-induced platelet inhibition was measured serially by means of 3 assays: 1) GP IIb-IIIa receptor occupancy, 2) binding of the activated GP IIb-IIIa-specific monoclonal antibody PAC1, and 3) agglutination of platelets with fibrinogen-coated beads (RPFA). Forty patients were randomly allocated to receive either UFH (70 U/kg) or dalteparin (60 IU/kg), followed by a half dose of abciximab (0.125 mg/kg) administered twice at 10-minute intervals. Assays were obtained 10 minutes after each half dose of abciximab and 8 to 10 and 24 hours after abciximab administration. RESULTS: No differences between UFH and dalteparin were observed. At each time-point measured, the mean percent platelet inhibition as determined by means of the receptor occupancy assay and PAC1 binding assay was less than the degree of inhibition determined by means of the RPFA. CONCLUSIONS: The results of targeted levels of platelet inhibition cannot be extrapolated between different clinical trials of GP IIb-IIIa antagonists unless the same assay is used. Dalteparin, compared with UFH, does not enhance platelet inhibition or receptor occupancy by abciximab, as demonstrated by means of 3 separate assays.

Development of an analytical methodology for sarin (GB) and soman (GD) in various military-related wastes.

The Army requires analytical methods that can detect chemical agents down to the low part-per-billion (ppb) levels in their waste streams in order to meet various state regulations regarding the classification of hazardous waste. Analytical methods were developed for the measurement of sarin (GB) and soman (GD) at ppb levels that involved preconcentration of relatively large volumes (40-150 microliters) of a chloroform extract onto a sorbent cartridge, followed by thermal desorption and analysis by GC-flame photometric detection. Certified reporting limits (CRLs) achieved with these methods ranged from 8.3 to 19 ppb for GB and from 1.8 to 5.3 ppb for GD in the three matrices screened. Method detection limits (MDLs) achieved with these methods ranged from 1.7 to 8.2 ppb for GB and from 0.39 to 1.2 ppb for GD. The methods are capable of achieving lower CRLs and MDLs with only minor modification.

Durable clinical benefit following Sr90 Beta irradiation therapy for in-stent restenosis in high-volume community practice.

Although randomized clinical trials have demonstrated efficacy of coronary irradiation versus placebo for the treatment of in-stent restenosis (ISR), durable long-term benefit in community practice is less well defined. From January 1, 2001, through June 30, 2002, consecutive percutaneous coronary intervention (n = 3,869) were analyzed at our center with a total of 330 patients undergoing coronary irradiation for ISR (53, Ir192; 12, P32; 265 Novoste Sr90). Novoste Sr90 was successfully performed in 265 of 270 (98%) of patients attempted by 10 operators. The mean patient age was 63 years (range 35 90) with 55% male (145/265) and 45% female (120/265). ISR anatomic subsets included multi-lesion (45/265; 17%), multi-vessel (27/265; 10.0%) and saphenous vein graft (16/265; 6.0%) interventions. At a mean follow-up of 10.5 2.8 (SD) months, fifty-three (20%) of the Novoste Sr90 treated patients had returned for symptoms requiring repeat angiography. Of these, 23 patients had repeat percutaneous coronary intervention (PCI) including 2 target site revascularizations (TSR), twelve non-TSR (distinct from the radiated segment of the target vessel), and 9 non-target vessel revascularizations (TVR). Coronary artery bypass surgery was performed in 11 total patients, 4 due to TSR, and 7 due to non-TVR. Clinical TSR was 2.3% (6/265) and TVR was 6.8% (18/265). In conclusion, the Novoste SR90 Beta-Cath System for the treatment of ISR is associated with a high procedural success rate and low TSR and TVR. Revascularization in follow-up is predominantly due to progressive disease outside the radiated segment and aggressive secondary prevention, especially prolonged anti-platelet therapy, appear critical to long-term procedural success.

Plasma levels of cortisol and corticosteroid-binding globulin (CBG) and hepatic CBG mRNA expression in pre- and postnatal pigs.

The relationships among hepatic corticosteroid-binding globulin (CBG) mRNA expression and plasma concentrations of cortisol and CBG was evaluated in fetal pigs (n=7-14 per age) on days 50, 70, 80, 90, and 104 of gestation and postnatal pigs (n=8 per age) on days 1, 3, 10, 20, 30, and 40 following birth. In fetal pigs, hepatic CBG mRNA expression was highest (P<0.01) on day 50 as compared to days 90 and 104, exhibiting an overall negative relationship (r=-0.63; P<0.01) with estimated gestation age. Plasma porcine CBG (pCBG) concentration was correlated (r=0.34; P<0.05) with hepatic CBG mRNA level. Plasma cortisol concentrations were not different over this same period. In postnatal pigs, hepatic CBG mRNA expression increased (P<0.01) from days 3 to 40. The pCBG concentration increased (P<0.01) from days 1 (6.1+/-3.4 microg/ml) to 10 (15.1+/-3.7 microg/ml), while plasma cortisol concentration remained constant. An understanding of the relation between hepatic CBG mRNA and circulating pCBG concentrations may provide insight into the mechanisms determining the bioavailability of cortisol necessary in prenatal development and the conservation of cortisol during postnatal development in the pig.

Mercury transformations in chemical agent simulant as characterized by X-ray absorption fine spectroscopy.

Chemical analyses of U.S. stockpiled mustard chemical warfare agent show some agent destined for destruction contains mercury [L. Ember, Chem. Eng. News 82 (2004) 8]. Because of its toxicity, mercury must be removed from agent prior to incineration or be scrubbed from incineration exhaust to prevent release into the atmosphere. Understanding mercury/agent interactions is critical if either atmospheric or aqueous treatment processes are used. We investigate and compare the state of mercury in water to that in thiodiglycol, a mustard simulant, as co-contaminants are introduced. The effects of sodium hypochlorite and sodium hydroxide, common neutralization chemicals, on mercury in water and simulant with and without co-contaminants present are examined using X-ray absorption fine spectroscopy (XAFS).