Enhanced intracoronary thrombolysis with urokinase using a novel, local drug delivery system. In vitro, in vivo, and clinical studies

BACKGROUND: Current pharmacological regimens for treating intracoronary thrombus in the cardiac catheterization laboratory generally involve the administration of thrombolytic agents that result in a systemic fibrinolytic state and/or require prolonged arterial drug infusion. The purpose of the present study was to assess a new technique for treating intracoronary thrombus consisting of the local infusion of limited quantities of urokinase with a novel drug delivery device. METHODS AND RESULTS: THe Dispatch coronary infusion catheter is a new local drug delivery system that allows for the prolonged infusion of therapeutic agents at an angioplasty site while distal coronary flow is maintained. Three experimental protocols were performed to determine the in vitro, in vivo, and clinical efficacy of this device. First, in vitro thrombolysis of fresh, porcine thrombus trapped in a 4-mm plastic tube with a 50% constriction and perfused with 20% porcine plasma was measured. Twenty-three thrombi were weighed before and after no treatment (n = 5), "systemic" urokinase administration (n = 4), local infusion of 150,000 U urokinase with a standard end-hole catheter (n = 4), local infusion of saline with the Dispatch catheter (n = 5), and local infusion of 150,000 U urokinase with the Dispatch catheter (n = 5). Second, 25 porcine coronary arteries in 23 pigs were dilated in vivo with conventional balloon angioplasty and then treated with 123I-labeled urokinase that was administered either by the Dispatch catheter (150,000 U; n = 16), intravenous systemic bolus (1,000,000 U; n = 3), guiding catheter infusion (500,000 U; n = 3), or local end-hole catheter infusion (150,000 U; n = 3). All vessels were subsequently harvested to quantify intramural deposition and subsequent washout of urokinase at the angioplasty site. Finally, 19 patients with angiographic evidence of intracoronary thrombus were treated with local urokinase infusion with the Dispatch catheter either before or after balloon angioplasty or directional atherectomy. In vitro studies demonstrated that infusion of urokinase with the Dispatch catheter decreased thrombus weight by 66% compared with no treatment (-25%), "systemic" urokinase administration (25%), end-hole catheter urokinase infusion (32%), or infusion of saline by the Dispatch catheter (32%) (P < or = .005). In vivo studies demonstrated immediate deposition of 0.12% of the urokinase delivered by the Dispatch catheter to the angioplasty site, compared with 0.0007% with systemic bolus, 0.003% with guiding catheter infusion, and 0.007% with local infusion with an end-hole catheter (P < .001). Urokinase deposited by the Dispatch catheter persisted intramurally for at least 5 hours. Patient studies demonstrated reduction of thrombus-containing stenoses and complete disappearance of intracoronary thrombus in all cases in which 150,000 U urokinase was locally infused over 30 minutes. There was no evidence of abrupt closure, distal embolization, or no reflow in any patient. CONCLUSIONS: Local urokinase delivery with the Dispatch catheter can result in rapid and complete intracoronary thrombolysis using substantially less drug than standard thrombolytic techniques. Intramural deposition of drug with this technique creates a local reservoir of urokinase that may provide prolonged thrombolytic activity at the infusion site.     

Effects of process parameter variations on the removal rate in chemical mechanical polishing of 4H-SiC

The effects of temperature, slurry pH, applied pressure, and polishing rotation rate on the material removal rate during chemical mechanical polishing (CMP) of 4H-silicon carbide wafers using colloidal silica slurry and polyurethane/polyester fiber polishing pads have been studied. Measured removal rates varied from around 100 Å/hr to nearly 2500 Å/hr depending on the values of the various parameters. The amount of material removed was determined by measuring the wafer mass before and after polishing. Variations in temperature and slurry pH did not produce significant changes in the measured removal rates. Higher polishing pressures resulted in increased material removal rates from 200 to 500 Å/hr but also produced excessive polishing pad damage. Variations in pad rotational speeds produced the largest changes in material removal rates, from around 200 to around 2000 Å/hr for rotational speeds between 60 and 180 rpm, but the variations were non-linear and somewhat inconsistent. This CMP formula is shown to consistently produce damage free surfaces but the optimum removal rate is slow.     

Designing Phase Selectively Soluble Polymer-Supports for Dimethylaminopyridine and Phosphine-Ligated Pd(0) Catalysts

Soluble poly(4-alkylstyrene) containing 4-methyl-, 4-tert-butyl, 4-dodecyl-, and 4-octadecylstyrene were formed either with monomers containing dyes-, ligands, or catalysts or with 5–10 mol% of 4-chloromethylstyrene and studied as supports for ligands or catalysts. Studies with dye-labeled polymers showed that polymers containing longer alkyl groups alone or at ca. 10 mol% loading are highly soluble in heptane can be used to separate and recycle organo- and transition metal catalysts.     

Studies of interfacial layers between 4H-SiC (0 0 0 1) and graphene

The region between epitaxial graphene and the SiC substrate has been investigated. 4H-SiC (0 0 0 1) samples were annealed in a high temperature molecular beam epitaxy system at temperatures between 1100 and 1700 °C. The interfacial layers between the pristine SiC and the graphene layers were studied by X-ray photoelectron spectroscopy. Graphene was found to grow on the SiC surface at temperatures above 1200 °C. Below this temperature, however, sp³ bonded carbon layers were formed with a constant atomic Si concentration. C1s and Si2p core level spectra of the graphene samples suggest that the interface layer we observe has a high carbon concentration and its thickness increases during the graphitization process. A significant concentration of Si atoms is trapped in the interface layer and their concentration also increases during graphitization.     

High field activation of micropipes in high resistivity silicon carbide

Micropipes in high resistivity (p≥5 kΩcm) SiC are highly activated in parallel electric fields (vertical devices) at room temperature starting at very low fields of 5-10 kV/cm, especially in the doped material. No activation of micropipes is observed in high fields (>100 kV/cm) perpendicular to their orientation (lateral devices). In the last case, the high field limitation is due to surface flashover phenomena taking place at 100-175 kV/cm in vacuum ambient and depending strongly on the material growth technology and the gap length. Non-ohmic behavior was not observed in lateral devices up to high applied fields. The high field characterization method is proposed as a powerful tool for the evaluation of the quality of SiC material for next-generation high voltage/high power devices.     

Pain-reducing properties of rewarding electrical brain stimulation in the rat.

In 4 experiments with 13 male Charles River rats, electrodes implanted along the medial forebrain bundle were screened for self-stimulation and stimulation-induced analgesia. Analgesia was defined by changes in unconditioned or escape responses to footshock. Almost all electrodes produced both self-stimulation and analgesia or neither. Thresholds for the 2 effects were highly correlated. Brain stimulation produced an analgesic aftereffect comparable in duration with the poststimulation enhancement of performance in self-stimulation (the priming effect). The refractory period of neurons underlying analgesia, assessed by behavioral means, was similar to that previously found for the priming effect in self-stimulation (.8-1.2 msec). Results suggest a common neural system mediating electrical analgesia and the priming effect of self-stimulation. (25 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Carbon structural transitions and ohmic contacts on 4H-SiC

The structural properties of sputtered carbon films on SiC are investigated using X-ray photoelectron spectroscopy (XPS) and Raman scattering. The as-deposited films are amorphous with an sp²/sp³ ratio of 1. The sp² carbon structures gradually increase with increasing temperatures and consist of amorphous aromatic-like carbon, polyene-like carbon, and nano-size graphite flakes. Schottky contacts on carbon/SiC are converted to ohmic contacts after annealing. The concentration of nano-graphitic flakes relative to the aromatic-like and polyene-like carbon increases nearly linearly with annealing temperature. Stacked graphitic structures are not observed. The specific contact resistivities are at 10⁻³–10⁻⁴Ωcm² on the carbon/SiC after annealing from 1050°C to 1350°C.     

ENDO-LAB: an integrated, portable endocrinology laboratory software system

ENDO-LAB is an IBM PC-based system which performs calculations and record-keeping for the Vanderbilt University Medical Center Endocrinology Laboratory. It manages maintenance and quality control, and prints reports for regulatory agencies. The system was designed to minimize paperwork without changing laboratory procedures in any way. Key features of ENDO-LAB include a uniform user interface, and error detection mechanisms. The system is designed to detect data which has been incorrectly entered. In addition, where the efficacy of a test can be determined on the basis of limited data, preliminary graphs are screened as soon as possible, so that the user can terminate lengthy calculations whose outcome would be invalid or inconclusive. ENDO-LAB is an integrated system in that the same statistical and calibration programs can be applied to all of the analyses. The system is both extensible and portable; it has been successfully implemented outside Vanderbilt.     

Observation of differences in the quenching of the Photocurrent in GaAs containing EL2 and EL0

The quenching of the photocurrent and photo-Hall effect of several undoped semi-insulating gallium arsenide samples has been measured and compared with the deep-level photoluminescence spectra from neighboring samples. Samples that show either EL2 (0.68 eV) or ELO (0.63 eV) photoluminescence have distinctly different photocurrent quenching behaviors. EL2 samples show a photocurrent decrease of several orders of magnitude, and a change fromn-type to p-type conduction during quenching at 80 K with 1.1 eV light. ELO samples show a reduction in photocurrent of less than an order of magnitude with no change in the carrier type at this temperature. Photo-Hall effect experiments at 80 K indicate that the conduction isn-type for the ELO samples, but changes fromn- to p-type during the quench for the EL2 samples. The temperature dependence of the quenching has also been studied. EL2 samples show little variation in the range 10-80 K, while ELO samples show significant quenching similar to EL2 after the temperature is reduced below 70 K. These results indicate that defects other than EL2 can significantly affect photocurrent quenching experiments.