Biomedical subjects
Publications and source records attributed to Stephen J Green.
Ferrocene-containing amidopyridine receptors bind carboxylic acids and the amino acid phenylalanine in acetonitrile via a novel proton transfer process that enables guests to be electrochemically sensed by positive shifts in the ferrocene-centred redox potentials.
BACKGROUND: Percutaneous coronary rotational atherectomy (PCRA) is a potent stimulus of platelet activation and aggregation in vivo. For this reason, many patients undergoing PCRA are treated with platelet glycoprotein (GP) IIb/IIIa inhibitors. However, there is limited data regarding the ability of GP IIb/IIIa inhibitors to reduce ischemic complications of PCRA and no data regarding their effect on long-term survival. METHODS: Data on 1138 consecutive patients undergoing PCRA in 5 hospitals in 1998-1999 were pooled and analyzed. Long-term survival was available for all 530 patients treated in 3 of the hospitals. RESULTS AND CONCLUSIONS: GP IIb/IIIa inhibitors were administered to 315 of 1138 (28%) PCRA patients. There was no difference in age, gender or race among patients treated with and without GP IIb/IIIa antagonists. The prevalence of hypertension, diabetes, renal insufficiency and peripheral vascular disease did not differ between groups. Unstable angina was more common among patients treated with GP IIb/IIIa inhibitors (45% vs. 38%, P = 0.036) Patients treated with GP IIb/IIIa inhibitors had lower ejection fractions (50% vs. 55%, P < 0.001) and more 3-vessel coronary disease (24% vs. 16%, P = 0.002). Angiographic success was over 99% in both groups (P = NS). The frequency of major adverse cardiovascular events (MACE) was slightly greater in GP IIb/IIIa inhibitor treated patients (3.8% vs. 2.2%, P = 0.126). At a mean follow-up of 3 years, mortality was 13.3% in the GP IIb/IIIa treated patients and 12% in the untreated patients (P = 0.224). On Cox proportional hazards analysis, treatment with a GP IIb/IIIa inhibitor was not significantly associated with increased survival (Hazard Ratio, 0.81, 95% Confidence Interval, 0.631-1.039, P = 0.098). These data do not indicate a significant association between GP IIb/IIIa inhibitor treatment during PCRA and MACE or survival. CONDENSED ABSTRACT: There is limited data regarding the ability of GP IIb/IIIa inhibitors to reduce ischemic complications of percutaneous coronary rotational atherectomy (PCRA) and no data regarding their effect on long-term survival. These data do not indicate a significant association between GP IIb/IIIa inhibitor treatment during PCRA and MACE or survival.
A heterodifunctionalised ferrocene, containing a carboxylic acid and an amidopyridine unit, self-assembles in organic solvents through complementary hydrogen bonds.
A series of quinolinequinones bearing various substituents has been synthesized, and the effects of substituents on the metabolism of the quinones by recombinant human NAD(P)H:quinone oxidoreductase (hNQO1) was studied. A range of quinolinequinones were selected for study, and were specifically designed to probe the effects of aryl substituents at C-2. A range of 28 quinolinequinones 2-29 was prepared using three general strategies: the palladium(0) catalyzed coupling of 2-chloroquinolines, the classical Friedländer synthesis and the double-Vilsmeier reaction of acetanilides. One example of an isoquinolinequinone 30 was also prepared, and the reduction potentials of the quinones were measured by cyclic voltammetry. For simple substituents R(2) at the quinoline 2-position, the rates of quinone metabolism by hNQO1 decrease for R(2)=Cl>H approximately Me>Ph. For aromatic substituents, the rate of reduction decreases dramatically for R(2)=Ph>1-naphthyl>2-naphthyl>4-biphenyl. Compounds containing a pyridine substituent are the best substrates, and the rates decrease as R(2)=4-pyridyl>3-pyridyl>2-pyridyl>4-methyl-2-pyridyl>5-methyl-2-pyridyl. The toxicity toward human colon carcinoma cells with either no detectable activity (H596 or BE-WT) or high NQO1 activity (H460 or BE-NQ) was also studied in representative quinones. Quinones that are good substrates for hNQO1 are more toxic to the NQO1 containing or expressing cell lines (H460 and BE-NQ) than the NQO1 deficient cell lines (H596 and BE-WT).
It is unknown whether the benefits of parenteral platelet glycoprotein (GP) IIb/IIIa inhibitors as an adjunct to percutaneous coronary intervention (PCI) demonstrated in randomized clinical trials extend to patients treated outside the setting of clinical trials. A contemporary registry of 10,847 consecutive PCI procedures was analyzed to determine the effect of GP IIb/IIIa inhibitor treatment on in-hospital major adverse coronary events ([MACEs] composite of death, urgent coronary artery bypass surgery, periprocedural myocardial infarction, abrupt closure, and stent thrombosis). In this registry, GP IIb/IIIa inhibitors were administered to 20.1% of patients. These patients were younger, more often men, and less often hypertensive than untreated patients. GP IIb/IIIa inhibitor-treated patients were more likely to present with acute myocardial infarction or unstable angina. Stents were placed in 79% of patients treated with GP IIb/IIIa inhibitors. MACEs occurred in 7.8% of GP IIb/IIIa inhibitor-treated patients compared with 3.8% of untreated patients (p <0.001). After multivariable adjustment for the propensity of GP IIb/IIIa inhibitor treatment as well as other possible confounders and interactions known to influence MACEs, GP IIb/IIIa inhibitor treatment was associated with a 57% increase in the risk of a MACE (odds ratio 1.57, 95% confidence interval 1.22 to 2.03; p = 0.0004). In a data set consisting of patients with a high degree of acuity predominantly treated with stent placement, GP IIb/IIIa inhibitor treatment is associated with an increase in thrombotic complications of PCI.
The cyclic voltammetry of ferrocene (CpFeCp) adsorbed as a monolayer of CpFeCpCO2(CH2)8SH, self-assembled onto the Hg-based high-temperature superconductor Hg0.8Re0.2Ba2Ca2Cu3O10 (Tc = 134 K), via an ultrathin (3.1 nm) Ag film, has been performed in liquid electrolyte (16:7:1 EtCl/THF/2-MeTHF; 0.2 M LiBF4) at a range of temperatures spanning the superconducting transition. Kinetic analysis based on the Marcus density-of-states theory affords standard heterogeneous rate constants, k degrees , for the ferrocene/ferricinium electron-transfer reaction. Casting these data in Arrhenius form yields a value of k degrees (273 K) = 357 s-1, which is 10-fold lower than that previously reported for the same reaction at a metal electrode in a similar electrolyte, while the reorganizational energy of 0.92 eV for the superconductor interface is very close to that for the related metal interface of 0.95 eV. There is, however, no effect of the onset of superconductivity on the electron-transfer rate for this system; the Arrhenius plot is linear through Tc. This is the first sub-Tc electrochemistry of any kind on a Hg-based superconductor and demonstrates the ease with which kinetic data can be obtained for these very high-Tc materials, opening the way for the routine study of a range of electron-transfer reactions as novel probes of the superconducting state.
The first kinetic measurements for electron transfer (ferrocene/ferricinium reaction) at the interface between an HTSC (Tl,Pb1223) and a redox polymer (ferrocene-tagged poly-pyrrole) show that superconductivity affects electron transfer rate, which thus offers a novel probe of the superconducting state.
Coronary heart disease is the leading cause of death among the elderly (> 65 years) and the very elderly (> 85 years). Little information is available regarding the outcome of very elderly patients referred for PCI in the current era of improved techniques, devices, and pharmacotherapy. The objective of the current study was to evaluate the clinical characteristics and outcomes of very elderly patients > or = 85 years of age in a large, contemporary, multi-institutional PCI database. Five hospitals in the New York City metropolitan area contributed these prospectively defined data elements on consecutive patients undergoing PCI from 1 January 1998 to 1 October 1999. Of 10,847 patients, 5,341 (49%) were younger than 65 years, 3,342 (31%) were 65-74 years, 1,885 (17%) were 75-84 years, and 279 (2.6%) were at least 85 years of age. Following PCI, the very elderly developed stroke (P < 0.001) and renal failure requiring dialysis (P = 0.002) more commonly than younger patients following PCI. The very elderly had a significantly increased in-hospital mortality rate at 2.5% (P < 0.001). However, on multivariate analysis, age > or = 85 years was not an independent predictor of in-hospital mortality (OR = 1.22; 95% CI = 0.37-4.07). The very elderly should not be refused PCI on the basis of advanced age alone.