Impact of Regional Systems of Care on Disparities in Care Among Female and Black Patients Presenting With ST-Segment-Elevation Myocardial Infarction.

Background: The American Heart Association Mission: Lifeline STEMI (ST-segment-elevation myocardial infarction) Systems Accelerator program, conducted in 16 regions across the United States to improve key care processes, resulted in more patients being treated within national guideline goals (time from first medical contact to device: <90 minutes for direct presenters to hospitals capable of performing percutaneous coronary intervention; <120 minutes for transfers). We examined whether the effort reduced reperfusion disparities in the proportions of female versus male and black versus white patients.

Methods And Results: In total, 23 809 patients (29.

Prognostic significance of blood markers of inflammation in patients with ST-segment elevation myocardial infarction undergoing primary angioplasty and effects of pexelizumab, a C5 inhibitor: a substudy of the COMMA trial.

Aims: Pexelizumab, a monoclonal antibody inhibiting C5, reduced 90 day mortality and shock in the COMplement inhibition in Myocardial infarction treated with Angioplasty (COMMA) trial without apparent reductions in infarct size. Inflammation is a critical component of ST-elevation myocardial infarction (STEMI); this substudy examines prognostic values of selected markers and treatment effects.

Methods And Results: C-reactive protein, interleukin-6 (IL-6), and tumour necrosis factor-alpha (TNF-alpha) serum levels were assessed in 337 patients enrolled in either the placebo or the pexelizumab 24 h infusion group.

Impact of a critical pathway on acute myocardial infarction quality indicators.

Study Objective: To determine the impact of a critical pathway on acute myocardial infarction (AMI) quality indicators.

Design: Retrospective chart review.

Setting: Large university hospital.

Coronary Angioplasty.

Percutaneous revascularization is a widely accepted procedure to treat patients with coronary artery disease. Since its first description in the 1970s, significant technological and pharmaceutical advances have occurred and subsequently reduced the complications associated with the procedure. Large, randomized controlled trials have provided additional evidence that percutaneous revascularization improves morbidity and mortality in patients with coronary artery disease.

Optimal deployment of third-generation stents: an intravascular ultrasound assessment.

Third-generation intracoronary stents allow deployment at higher pressures, possibly obviating the need for high-pressure postdilations and also possibly reducing restenosis. This study evaluated the ability of the Tristar Coronary Stent System to produce optimal stent deployment as measured by intravascular ultrasound (IVUS) and quantitative coronary angiography in 46 patients. Optimal stent deployment was defined as minimal luminal area > 80% of the average of the proximal and distal reference luminal areas.

Polyethylene glycol diisocyanate decreases platelet deposition after balloon injury of rabbit femoral arteries.

Background: Platelet deposition after angioplasty remains problematic and may contribute to intimal hyperplasia and restenosis. We proposed that polyethylene glycol diisocyanate (PEG-DISO), a polymer that rapidly forms covalent linkages with amine residues on proteins, could mask thrombogenic vascular wall proteins from platelets, thereby abrogating acute platelet deposition.

Methods And Results: To test this hypothesis, we isolated the femoral arteries of 10 New Zealand White rabbits and injured them with 3 passes of a 2F Fogarty catheter which was inserted through a distal arteriotomy.

Four-dimensional analysis of cyclic changes in coronary artery shape.

The objective of this study was to derive a method for quantifying the dynamic geometry of coronary arteries. Coronary artery geometry plays an important role in atherosclerosis. Coronary artery geometry also influences the performance of coronary interventions.

An iron-binding exochelin prevents restenosis due to coronary artery balloon injury in a porcine model.

Background- Vascular smooth muscle cell (VSMC) proliferation is a critical factor in the neointima formation that causes restenosis after coronary angioplasty (PTCA). Desferri-exochelin 772SM (D-EXO), a highly diffusible, lipophilic iron chelator secreted by Mycobacterium tuberculosis, inhibits proliferation of VSMCs in culture. We hypothesized that treatment with D-EXO would inhibit neointima formation in balloon-injured vessels in vivo.

3D coronary reconstruction from routine single-plane coronary angiograms: clinical validation and quantitative analysis of the right coronary artery in 100 patients.

Background: Current coronary angiographic techniques display complex three-dimensional (3D) coronary structures in two dimensions (2D). We have developed a 3D reconstruction (3DR) algorithm using standard single-plane angiographic images that allows for 3D display of coronary structures. The purpose of this study was to validate our 3DR algorithm and quantify anatomic characteristics of the right coronary artery (RCA) in vivo.

Predictors of death and reinfarction at 30 days after primary angioplasty: the GUSTO IIb and RAPPORT trials.

Background: Thirty-day death among recipients of fibrinolytic therapy for acute myocardial infarction (MI) is tightly correlated with easily obtainable key demographic and clinical parameters such as age, blood pressure, heart rate, and infarct location. Similar data for primary angioplasty are not available.

Methods And Results: Data from 2 large, contemporary, primary angioplasty trials were formally combined and analyzed with respect to death and death/repeat MI at 30 days through the use of multivariate logistic regression models.

Effect of abciximab on the pattern of reperfusion in patients with acute myocardial infarction treated with primary angioplasty. RAPPORT investigators. ReoPro And Primary PTCA Organization and Randomized Trial.

We investigated the effect of platelet fibrinogen receptor blockade on infarct size after primary angioplasty. Abciximab significantly reduced the time-to-peak creatine kinase without affecting enzymatic infarct size, suggesting a beneficial effect on the pattern and speed of reperfusion.

Feasibility of combined percutaneous transluminal angioplasty and minimally invasive direct coronary artery bypass in patients with multivessel coronary artery disease.

Background: Angioplasty has become an accepted treatment of patients with coronary artery disease and is now commonly used to treat patients with multivessel disease. The major disadvantage of angioplasty has been restenosis requiring repeat interventions with resultant loss of initial cost savings. Compared with the right and the circumflex coronary arteries, the left anterior descending artery (LAD) has been more adversely affected by restenosis.

Randomized, placebo-controlled trial of platelet glycoprotein IIb/IIIa blockade with primary angioplasty for acute myocardial infarction. ReoPro and Primary PTCA Organization and Randomized Trial (RAPPORT) Investigators.

Background: The benefit of catheter-based reperfusion for acute myocardial infarction (MI) is limited by a 5% to 15% incidence of in-hospital major ischemic events, usually caused by infarct artery reocclusion, and a 20% to 40% need for repeat percutaneous or surgical revascularization. Platelets play a key role in the process of early infarct artery reocclusion, but inhibition of aggregation via the glycoprotein IIb/IIIa receptor has not been prospectively evaluated in the setting of acute MI.

Methods And Results: Patients with acute MI of <12 hours' duration were randomized, on a double-blind basis, to placebo or abciximab if they were deemed candidates for primary PTCA.

Effect of direct thrombin inhibition with Bivalirudin (Hirulog) on restenosis after coronary angioplasty.

The direct antithrombin, bivalirudin, did not reduce angiographic restenosis measured either as the dichotomous restenosis rate of 62% for bivalirudin and 58% for heparin (p = 0.70), or as the late loss in lumen diameter of 0.44 +/- 0.

The lack of effect of beta-carotene on restenosis in cholesterol-fed rabbits.

The success of percutaneous transluminal coronary angioplasty is limited by restenosis in 30-50% of cases. Cellular production of reactive oxygen species at the site of injury has been implicated as a contributing factor in the process of restenosis. beta-Carotene is a lipid-soluble antioxidant whose effects on this process have not been previously investigated.

Nucleosides. CXXXV. Synthesis of some 9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-9H-purines and their biological activities.

Seven purine nucleosides containing the 2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl moiety were synthesized and tested for their antitumor activity. Direct condensation of 3-O-acetyl-5-O-benzoyl-2-deoxy-2-fluoro-D-arabinofuranosyl bromide (1) with N6-benzoyladenine in CH2Cl2 followed by saponification of the product afforded the adenine nucleoside (I, 2'-F-ara-A). Deamination of I with NaNO2 in HOAc gave the hypoxanthine analogue (II, 2'-F-ara-H).

Phase I trial of alpha-difluoromethyl ornithine (DFMO) and methylglyoxal bis (guanylhydrazone) (MGBG) in patients with advanced prostatic cancer.

Both alpha-difluoromethyl ornithine (DFMO) and methylglyoxal bis (guanylhydrazone) (MGBG) inhibit sequential enzymatic reactions in the pathway of polyamine biosynthesis. Since polyamines may be important factors in proliferation of cancer cells and DFMO combined with MGBG has shown synergistic cytotoxicity in an experimental prostatic tumor, we evaluated these agents in phase I clinical trial involving 5 patients with advanced, hormone-resistant prostatic cancer. Toxic reaction to combined DFMO and MGBG was dose-related and included nausea, fatigue, and diarrhea especially with the higher doses of MGBG.

Synthesis and biological activities of 5-deaza analogues of aminopterin and folic acid.

N-[p-[[(2,4-Diaminopyrido[2,3-d]pyrimidin-6-yl)methyl] amino]benzoyl]-L-glutamic acid (1a, 5-deazaaminopterin) and the 5-methyl analogue (1b) were synthesized in 14 steps from 5-cyanouracil (4a) and 5-cyano-6-methyluracil (4b), respectively, by exploitation of the novel pyrimidine to pyrido[2,3-d]pyrimidine ring transformation reaction. The 5-cyanouracils 4 were treated with chloromethyl methyl ether to the 1,3-bis(methoxymethyl)uracils (5, which were treated with malononitrile in NaOEt/EtOH to give the pyrido[2,3-d]pyrimidines 6. Diazotization of 6 in concentrated HCl afforded the 7-chloro derivatives 8 in high yield.

Compensatory mutations in receptor function: a reevaluation of the role of methylation in bacterial chemotaxis.

During bacterial chemotaxis membrane receptor proteins are methylated and demethylated at glutamate residues. The generally accepted view is that these reactions play an essential role in the chemosensing mechanism. Strains may be isolated, however, that exhibit chemotaxis in the complete absence of methylation.

Stimulation of Rauscher leukemia virus DNA polymerase DNA-directed DNA synthesis by cationic trypanocides and polyamines.

Activated DNA-directed DNA synthesis catalyzed by Rauscher leukemia virus (RLV) and other type C mammalian retroviral DNA polymerases is uniquely stimulated by biologically active polyamines. Cationic trypanocides may act as antagonists of polyamine function. As described here, several cationic trypanocides stimulate RLV polymerase-catalyzed DNA-directed DNA synthesis at concentrations significantly inhibiting eukaryotic DNA polymerases.

Phase I trial of 1-(2'-deoxy-2'-fluoro-1-beta-D-arabinofuranosyl)-5-methyluracil (FMAU).

1-(2'-Deoxy-2'-fluoro-1-beta-D-arabinofuranosyl)-5-methyluracil (FMAU), a new pyrimidine nucleoside, is of potential clinical interest both as an anticancer and as an antiviral drug. FMAU is active in vitro and in vivo against P815 and L1210 cell lines resistant to cytarabine. Moreover, in mice inoculated ic with herpes simplex virus Type II, FMAU is 100-fold more potent than vidarabine or acyclovir.

Effects of alpha-difluoromethylornithine and methylglyoxal bis(guanylhydrazone) on the growth of experimental renal adenocarcinoma in mice.

alpha-Difluoromethylornithine (DFMO) and methylglyoxal bis-(guanylhydrazone) (MGBG) were tested against a murine renal adenocarcinoma, because polyamines are necessary for neoplastic cell growth and because human renal adenocarcinomas contain higher levels of spermidine than do normal renal cells; MGBG inhibits spermidine synthesis and has some activity against human renal tumors; DFMO irreversibly inhibits ornithine decarboxylase, the first rate-limiting enzyme controlling polyamine biosynthesis; and DFMO promotes intracellular accumulation of MGBG in experimental tumor models and human leukemia. DFMO (2%) in drinking water, MGBG (15 mg/kg i.p.

Phase-II trial of 1,2-diaminocyclohexane (4-carboxyphthalato) platinum (II) (DACCP) in non-small cell lung cancer.

A phase-II trial of the second-generation platinum analog 1,2-diaminocyclohexane (4-carboxyphthalato) platinum (II) (DACCP) was performed in 33 patients with non-small cell lung cancer. The compound was studied because of its lack of cross resistance in vitro and decreased nephrotoxicity in both preclinical testing and in a phase-I trial. The starting dose was 640 mg/m2 IV every 3 weeks, with escalations to 720 mg/m2 in the absence of toxicity.