Comparative accuracy of supine-only and combined supine-prone myocardial perfusion imaging in men.

BACKGROUND: Combined supine-prone myocardial perfusion imaging (CSP MPI) has been shown to reduce attenuation artifact in comparison to supine-only (SU) MPI in mixed-gender populations with varying risk for coronary artery disease (CAD), often where patients served as their own controls. However, there is limited direct comparison of these imaging strategies in men. METHODS: 934 male patients underwent CSP or SU MPI. Diagnostic certainty of interpretation was compared. Within the cohort, 116 were referred for left heart catheterization (LHC) to assess for CAD. Sensitivity, specificity, and area under the curve (AUC) were compared with additional analysis based on body mass index (BMI). RESULTS: 597 patients completed the SU protocol and 337 patients completed the CSP protocol. Equivocal studies were seen more frequently in the SU group (13%) than in the CSP group (4%, P < .001). At catheterization, the specificity for CSP MPI of 70% was higher than 40% for SU MPI (P = .032). The CSP AUC (0.80 ± 0.06) was significantly larger than SU AUC (0.57 ± 0.05, P = .004). CSP specificity was significantly higher in obese patients. CONCLUSIONS: CSP MPI increases diagnostic certainty and improves test accuracy for CAD detection in men with CAD risk factors, especially obese patients, compared to SU MPI.

Elucidating the Mechanism of Uranium Mediated Diazene N═N Bond Cleavage.

Investigation into the reactivity of reduced uranium species toward diazenes has revealed key intermediates in the four-electron cleavage of azobenzene. Trivalent Tp*2U(CH2Ph) (1a) (Tp* = hydrotris(3,5-dimethylpyrazolyl)borate) and Tp*2U(2,2'-bpy) (1b) both perform the two-electron reduction of diazenes affording η2-hydrazido complexes Tp*2U(AzBz) (2-AzBz) (AzBz = azobenzene) and Tp*2U(BCC) (2-BCC) (BCC = benzo[c]cinnoline) in contrast to precursors of the bis(Cp*) (Cp* = 1,2,3,4,5-pentamethylcyclopentadienide) ligand framework. The four-electron cleavage of diazenes to give trans-bis(imido) species was possible by using Cp*U(MesPDIMe)(THF) (3) (MesPDIMe = 2,6-((Mes)N═CMe)2-C5H3N, Mes = 2,4,6-trimethylphenyl), which is supported by a highly reduced trianionic chelate that undergoes electron transfer. This proceeds via concerted addition at a single uranium center supported by both a crossover experiment and through addition of an asymmetrically substituted diazene, Ph-N═N-Tol. Further investigation of 3 and its substituted analogue, Cp*U(tBu-MesPDIMe)(THF) (3-tBu) (tBu-MesPDIMe = 2,6-((Mes)N═CMe)2-p-C(CH3)3-C5H2N), with benzo[c]cinnoline, revealed that the four-electron cleavage occurs first by a single electron reduction of the diazene with the redox chemistry performed solely at the redox-active pyridine(diimine) to form dimeric [Cp*U(BCC)(MesHPDIMe)]2 (5) and Cp*U(BCC)(tBu-MesPDIMe) (6). While a transient pyridine(diimine) triplet diradical in the formation of 5 results in H atom abstraction and p-pyridine coupling, the tert-butyl moiety in 6 allows for electronic rearrangement to occur, precluding deleterious pyridine-radical coupling. The monomeric analogue of 5, Cp*U(BCC)(MesPDIMe) (7), was synthesized via salt metathesis from Cp*UI(MesPDIMe) (3-I). All complexes have been characterized by 1H NMR and electronic absorption spectroscopies, X-ray diffraction, and, where pertinent, EPR spectroscopy. Further, the electronic structures of 3-I, 5, and 7 have been investigated by SQUID magnetometry.

Discovery of highly selective alkyne semihydrogenation catalysts based on first-row transition-metallated porous organic polymers.

Five different first-row transition metal precursors (V(III), Cr(III), Mn(II), Co(II), Ni(II)) were successfully incorporated into a catechol porous organic polymer (POP) and characterized using ATR-IR and XAS analysis. The resulting metallated POPs were then evaluated for catalytic alkyne hydrogenation using high-throughput screening techniques. All POPs were unexpectedly found to be active and selective catalysts for alkyne semihydrogenation. Three of the metallated POPs (V, Cr, Mn) are the first of their kind to be active single-site hydrogenation catalysts. These results highlight the advantages of using a POP platform to develop new catalysts which are otherwise difficult to achieve through traditional heterogeneous and homogeneous routes.

Tris(phosphinoamide)-supported uranium-cobalt heterobimetallic complexes featuring Co → U dative interactions.

A series of tris- and tetrakis(phosphinoamide) U/Co complexes has been synthesized. The uranium precursors, (η(2)-Ph2PN(i)Pr)4U (1), (η(2)-(i)Pr2PNMes)4U (2), (η(2)-Ph2PN(i)Pr)3UCl (3), and (η(2)-(i)Pr2PNMes)3UI (4), were easily accessed via addition of the appropriate stoichiometric equivalents of [Ph2PN(i)Pr]K or [(i)Pr2PNMes]K to UCl4 or UI4(dioxane)2. Although the phosphinoamide ligands in 1 and 4 have been shown to coordinate to U in an η(2)-fashion in the solid state, the phosphines are sufficiently labile in solution to coordinate cobalt upon addition of CoI2, generating the heterobimetallic Co/U complexes ICo(Ph2PN(i)Pr)3U[η(2)-Ph2PN(i)Pr] (5), ICo((i)Pr2PNMes)3U[η(2)-((i)Pr2PNMes)] (6), ICo(Ph2PN(i)Pr)3UI (7), and ICo((i)Pr2PNMes)3UI (8). Structural characterization of complexes 5 and 7 reveals reasonably short Co-U interatomic distances, with 7 exhibiting the shortest transition metal-uranium distance ever reported (2.874(3) Å). Complexes 7 and 8 were studied by cyclic voltammetry to examine the influence of the metal-metal interaction on the redox properties compared with both monometallic Co and heterobimetallic Co/Zr complexes. Theoretical studies are used to further elucidate the nature of the transition metal-actinide interaction.

Carbon-carbon reductive elimination from homoleptic uranium(IV) alkyls induced by redox-active ligands.

The synthesis, characterization, and reactivity of the homoleptic uranium(IV) alkyls U(CH(2)C(6)H(5))(4) (1-Ph), U(CH(2)-p-CH(3)C(6)H(4))(4) (1-p-Me), and U(CH(2)-m-(CH(3))(2)C(6)H(3))(4) (1-m-Me(2)) are reported. The addition of 4 equiv of K(CH(2)Ar) (Ar = Ph, p-CH(3)C(6)H(4), m-(CH(3))(2)C(6)H(3)) to UCl(4) at -108 °C produces 1-Ph in good yields and 1-p-Me and 1-m-Me(2) in moderate yields. Further characterization of 1-Ph by X-ray crystallography confirmed η(4)-coordination of each benzyl ligand to the uranium center. Magnetic studies produced an effective magnetic moment of 2.60 µ(B) at 23 °C, which is consistent with a tetravalent uranium 5f(2) electronic configuration. Addition of 1 equiv of the redox-active α-diimine (Mes)DAB(Me) ((Mes)DAB(Me) = [ArN═C(Me)C(Me)═NAr]; Ar = 2,4,6-trimethylphenyl (Mes)) to 1-Ph results in reductive elimination of 1 equiv of bibenzyl (PhCH(2)CH(2)Ph), affording ((Mes)DAB(Me))U(CH(2)C(6)H(5))(2) (2-Ph). Treating an equimolar mixture of 1-Ph and 1-Ph-d(28) with (Mes)DAB(Me) forms the products from monomolecular reductive elimination, 2-Ph, 2-Ph-d(14), bibenzyl, and bibenzyl-d(14). This is confirmed by (1)H NMR spectroscopy and GC/MS analysis of both organometallic and organic products. Addition of 1 equiv of 1,2-bis(dimethylphosphino)ethane (dmpe) to 1-Ph results in formation of the previously synthesized (dmpe)U(CH(2)C(6)H(5))(4) (3-Ph), indicating the redox-innocent chelating phosphine stabilizes the uranium center in 3-Ph and prevents reductive elimination of bibenzyl. Full characterization for 3-Ph, including X-ray crystallography, is reported.

Computational insights into uranium complexes supported by redox-active α-diimine ligands.

The electronic structures of two uranium compounds supported by redox-active α-diimine ligands, ((Mes)DAB(Me))(2)U(THF) (1) and Cp(2)U((Mes)DAB(Me)) (2) ((Mes)DAB(Me) = [ArN═C(Me)C(Me)═NAr]; Ar = 2,4,6-trimethylphenyl (Mes)), have been investigated using both density functional theory and multiconfigurational self-consistent field methods. Results from these studies have established that both uranium centers are tetravalent, that the ligands are reduced by two electrons, and that the ground states of these molecules are triplets. Energetically low-lying singlet states are accessible, and some transitions to these states are visible in the electronic absorption spectrum.

Synthesis, characterization, and multielectron reduction chemistry of uranium supported by redox-active α-diimine ligands.

Uranium compounds supported by redox-active α-diimine ligands, which have methyl groups on the ligand backbone and bulky mesityl substituents on the nitrogen atoms {(Mes)DAB(Me) = [ArN═C(Me)C(Me)═NAr], where Ar = 2,4,6-trimethylphenyl (Mes)}, are reported. The addition of 2 equiv of (Mes)DAB(Me), 3 equiv of KC(8), and 1 equiv of UI(3)(THF)(4) produced the bis(ligand) species ((Mes)DAB(Me))(2)U(THF) (1). The metallocene derivative, Cp(2)U((Mes)DAB(Me)) (2), was generated by the addition of an equimolar ratio of (Mes)DAB(Me) and KC(8) to Cp(3)U. The bond lengths in the molecular structure of both species confirm that the α-diimine ligands have been doubly reduced to form ene-diamide ligands. Characterization by electronic absorption spectroscopy shows weak, sharp transitions in the near-IR region of the spectrum and, in combination with the crystallographic data, is consistent with the formulation that tetravalent uranium ions are present and supported by ene-diamide ligands. This interpretation was verified by U L(III)-edge X-ray absorption near-edge structure (XANES) spectroscopy and by variable-temperature magnetic measurements. The magnetic data are consistent with singlet ground states at low temperature and variable-temperature dependencies that would be expected for uranium(IV) species. However, both complexes exhibit low magnetic moments at room temperature, with values of 1.91 and 1.79 µ(B) for 1 and 2, respectively. Iodomethane was used to test the reactivity of 1 and 2 for multielectron transfer. While 2 showed no reactivity with CH(3)I, the addition of 2 equiv of iodomethane to 1 resulted in the formation of a uranium(IV) monoiodide species, ((Mes)DAB(Me))((Mes)DAB(Me2))UI {3; (Mes)DAB(Me2) = [ArN═C(Me)C(Me(2))NAr]}, which was characterized by single-crystal X-ray diffraction and U M(4)- and M(5)-edge XANES. Confirmation of the structure was also attained by deuterium labeling studies, which showed that a methyl group was added to the ene-diamide ligand carbon backbone.

Synthesis and characterization of a uranium(III) complex containing a redox-active 2,2'-bipyridine ligand.

Hydrotris(3,5-dimethylpyrazolyl)borate uranium(III) diiodide derivatives have been prepared as an entry into low-valent uranium chemistry with these ligands. The bis(tetrahydrofuran) adduct, Tp*UI(2)(THF)(2) (1) (Tp* = hydrotris(3,5-dimethylpyrazolyl)borate), was synthesized by addition of sodium hydrotris(3,5-dimethylpyrazolyl)borate (NaTp*) to an equivalent of UI(3)(THF)(4). Addition of 2,2'-bipyridine (2,2'-bpy) to 1 displaced the THF molecules producing Tp*UI(2)(2,2'-bpy) (2). Both derivatives were characterized by (1)H NMR and IR spectroscopies, magnetic measurements, and X-ray crystallography. Reduction of both species was attempted with two equivalents of potassium graphite. The reduction of 1 did not result in a clean product, but rather decomposition and ligand redistribution. However, compound 2 was reduced to form Tp*(2)U(2,2'-bpy), 3, which is composed of a uranium(III) ion with a radical monoanionic bipyridine ligand. This was confirmed by X-ray crystallography, which revealed distortions in the bond lengths of the bipyridine consistent with reduction. Further support was obtained by (1)H NMR spectroscopy, which showed resonances shifted far upfield, consistent with radical character on the 2,2'-bipyridine ligand. Future studies will explore the reactivity of this compound as well as the consequences for redox-activity in the bipyridine ligand.

Crystallographic evidence of a base-free uranium(IV) terminal oxo species.

The uranium(IV) terminal oxo species Tp*(2)U(O) has been synthesized by oxygen-atom transfer from pyridine-N-oxide to Tp*(2)U(2,2'-bipyridine), a trivalent uranium species with a monoanionic bipyridine ligand. Full characterization of the oxo species using (1)H NMR and IR spectroscopies, X-ray crystallography, and computational studies was performed.

Immediate computed tomography coronary angiography versus delayed outpatient stress testing for detecting coronary artery disease in emergency department patients with chest pain.

Noninvasive testing for coronary artery disease (CAD) is warranted for symptomatic patients with intermediate pretest likelihood of CAD. Accomplishing testing in an emergency department (ED) environment is challenging. We compared two strategies of CAD testing in ED patients: immediate computed tomography coronary angiography (CTCA) versus delayed outpatient stress testing. We conducted a historical control cohort study comparing symptomatic ED patients without an acute coronary syndrome who warranted noninvasive CAD testing. Two cohorts (50 patients each) were defined by CAD testing strategy, immediate CTCA versus delayed stress testing. Outcomes were duration of ED stay, detection of CAD, and 3-month rates of readmission, myocardial infarction, (MI) or death. Median duration of stay was 417.5 minutes (interquartile range [IQR] 359.0-581.0) in the CT cohort and 400.0 minutes (IQR 338.0-471.0) in the control cohort (P = 0.53). CAD was detected in 14 CT cohort patients versus 1 in control (P = 0.0004), due to low follow-up in the control cohort (18 of 50, 36%). Obstructive CAD was diagnosed in 6 CT cohort patients versus 1 in control (P = 0.11). During 3 months of follow-up, four patients in each cohort were reevaluated in the ED for chest pain; no patients suffered MI or death. A strategy of immediate CTCA is superior to a delayed stress testing strategy for detecting CAD in ED patients with chest pain and prompting appropriate referrals for further management. Delayed stress testing was primarily ineffective due to low follow-up. Immediate CTCA can be used safely without altering the ED duration of stay.

Responsible use of computed tomography in the evaluation of coronary artery disease and chest pain.

Many options are available to clinicians for the noninvasive evaluation of the cardiovascular system and patient concerns about chest discomfort. Cardiac computed tomography (CT) is a rapidly advancing field of noninvasive imaging. Computed tomography incorporates coronary artery calcium scoring, coronary angiography, ventricular functional analysis, and information about noncardiac thoracic anatomy. We searched the PubMed database and Google from inception to September 2009 for resources on the accuracy, risk, and predictive capacity of coronary artery calcium scoring and CT coronary angiography and have reviewed them herein. Cardiac CT provides diagnostic information comparable to echocardiography, nuclear myocardial perfusion imaging, positron emission tomography, and magnetic resonance imaging. A cardiac CT study can be completed in minutes. In patients with a nondiagnostic stress test result, cardiac CT can preclude the need for invasive angiography. Prognostic information portends excellent outcomes in patients with normal study results. Use of cardiac CT can reduce health care costs and length of emergency department stays for patients with chest pain. Cardiac CT examination provides clinically relevant information at a radiation dose similar to well-established technologies, such as nuclear myocardial perfusion imaging. Advances in technique can reduce radiation dose by 90%. With appropriate patient selection, cardiac CT can accurately diagnose heart disease, markedly decrease health care costs, and reliably predict clinical outcomes.

Glomerular podocytopathy in patients with systemic lupus erythematosus.

A series of patients with systemic lupus erythematosus (SLE) and proteinuria were studied to determine whether nephrotic-range proteinuria was associated with diffuse epithelial cell foot process effacement in the absence of peripheral glomerular immune aggregate deposition. Biopsies from patients with known or suspected SLE and a histologic diagnosis of (1) normal by light microscopy, (2) mesangial proliferative glomerulonephritis, or (3) focal segmental glomerulosclerosis were studied. Biopsies were excluded when they demonstrated endocapillary proliferation or necrosis by light microscopy or electron-dense glomerular basement membrane deposits by electron microscopy. Patients were required to fulfill four of 11 American Rheumatologic Association criteria for the diagnosis of SLE, and proteinuria could not be associated with nonsteroidal anti-inflammatory drug use. Eighteen biopsies were studied, eight from patients with nephrotic-range proteinuria (>/=3 g/d) and 10 from patients with non-nephrotic proteinuria. The time from diagnosis of SLE to biopsy was shorter for nephrotic patients that for nonnephrotic patients. Seven of eight biopsies from nephrotic patients demonstrated at least 80% foot process effacement, whereas no biopsy from a nonnephrotic patient exhibited >20% effacement. There were no other significant pathologic differences between the nephrotic and nonnephrotic patients. The single common morphologic feature associated with nephrotic proteinuria was diffuse visceral epithelial cell foot process effacement. It is concluded that the development of nephrotic-range proteinuria in patients with SLE without peripheral immune aggregate deposition or endocapillary proliferation on renal biopsy is more likely a manifestation of SLE than the coexistence of idiopathic minimal-change glomerulopathy and SLE.