Impact of diabetes mellitus on acute outcomes of percutaneous coronary intervention in chronic total occlusions: insights from a US multicentre registry.

AIM: To examine the impact of diabetes mellitus on procedural outcomes of patients who underwent percutaneous coronary intervention for chronic total occlusion. METHODS: We assessed the impact of diabetes mellitus on the outcomes of percutaneous coronary intervention for chronic total occlusion among 1308 people who underwent such procedures at 11 US centres between 2012 and 2015. RESULTS: The participants' mean ± sd age was 66 ± 10 years, 84% of the participants were men and 44.6% had diabetes. As compared with participants without diabetes, participants with diabetes were more likely to have undergone coronary artery bypass graft surgery (38 vs 31%; P = 0.006), and to have had previous heart failure (35 vs 22%; P = 0.0001) and peripheral arterial disease (19 vs 13%; P = 0.002). They also had a higher BMI (31 ± 6 kg/m2 vs 29 ± 6 kg/m2 ; P = 0.001), similar Japanese chronic total occlusion scores (2.6 ± 1.2 vs 2.5 ± 1.2; P = 0.82) and similar final successful crossing technique: antegrade wire escalation (46 vs 47%; P = 0.66), retrograde (30 vs 28%; P = 0.66) and antegrade dissection re-entry (24 vs 25%; P = 0.66). Technical (91 vs 90%; P = 0.80) and procedural (89 vs 89%; P = 0.93) success was similar in the two groups, as was the incidence of major adverse cardiac events (2.2 vs 2.5%; P = 0.61). CONCLUSIONS: In a contemporary cohort of people undergoing percutaneous coronary intervention for chronic total occlusion, nearly one in two (45%) had diabetes mellitus. Procedural success and complication rates were similar in people with and without diabetes.

Molecular imaging of macrophage protease activity in cardiovascular inflammation in vivo.

Macrophages contribute pivotally to cardiovascular diseases (CVD), notably to atherosclerosis. Imaging of macrophages in vivo could furnish new tools to advance evaluation of disease and therapies. Proteolytic enzymes serve as key effectors of many macrophage contributions to CVD. Therefore, intravital imaging of protease activity could aid evaluation of the progress and outcome of atherosclerosis, aortic aneurysm formation, or rejection of cardiac allografts. Among the large families of proteases, matrix metalloproteinases (MMPs) and cysteinyl cathepsins have garnered the most interest because of their participation in extracellular matrix remodelling. These considerations have spurred the development of dedicated imaging agents for protease activity detection. Activatable fluorescent probes, radiolabelled inhibitors, and nanoparticles are currently under exploration for this purpose. While some agents and technologies may soon see clinical use, others will require further refinement. Imaging of macrophages and protease activity should provide an important adjunct to understanding pathophysiology in vivo, evaluating the effects of interventions, and ultimately aiding clinical care.

Mutual influence of cholesterol esterase and pseudocholinesterase on the biodegradation of dental composites.

It has been demonstrated that human saliva contains cholesterol esterase (CE)- and pseudocholinesterase (PCE)-like hydrolase activities. While PCE has been shown to preferentially degrade triethylene glycol dimethacrylate (TEGDMA) and its derivatives, CE has a greater catalytic effect on the breakdown of bis-phenol-A-diglycidyl dimethacrylate (bisGMA) components in composite dental resins. The current study seeks to determine if there is a mutual influence between the different esterases with respect to the biodegradation of resin composite. Photopolymerized model composite resin samples (containing 60% by weight fraction of silanated barium glass filler) based on bisGMA/TEGDMA (bis) or urethane-modified bisGMA/TEGDMA/bisEMA (ubis) monomers were incubated in buffer, CE and/or PCE solutions (pH=7.0, 37 degrees C) for 8 and 16 days. The incubation solutions were analyzed for degradation products using high-performance liquid chromatography, UV spectroscopy and mass spectrometry. In the bis system, higher amounts (p<0.05) of a bisGMA derived product, bishydroxy-propoxyphenyl-propane (bisHPPP), were detected in the combined enzyme group as compared to the sum of the two individual enzyme groups. In the ubis system, similar comparisons showed that higher levels (p<0.05) of bisHPPP were detected in the combined group at 8 days while higher amounts (p<0.05) of a bisEMA derived product, ethoxylated bis-phenol A, were detected in the combined group at 16 days. The study concluded that CE and PCE act synergistically to increase the biodegradation of both composite resin materials.

Interactions between resin monomers and commercial composite resins with human saliva derived esterases.

Cholesterol esterase (CE) and pseudocholinesterase (PCE) have been reported to degrade commercial and model composite resins containing bisphenylglycidyl dimethacrylate (BisGMA), triethylene glycol dimethacrylate (TEGDMA) or the latter in combination with urethane modified BisGMA monomer systems. In addition, human saliva has been shown to contain esterase like activities similar to CE and PCE. Hence, it was the aim of the current study to determine to what extent human saliva could degrade two common commercial composite resins (Z250 from 3M Inc. and Spectrum TPH from L.D. Caulk) which contain the above monomer systems. Saliva samples from different volunteers were collected, processed, pooled, and freeze-dried. TEGDMA and BisGMA monomers were incubated with human saliva derived esterase activity (HSDEA) and their respective hydrolysis was monitored using high performance liquid chromatography (HPLC). Both monomers were completely hydrolyzed within 25 h by HSDEA. Photopolymerized composites were incubated with buffer or human saliva (pH 7.0 and 37 C) for 2, 8 and 16 days. The incubation solutions were analyzed using HPLC and mass spectrometry. Surface morphology characterization was carried out using scanning electron microscopy. Upon biodegradation, the Z250 composite yielded higher amounts of BisGMA and TEGDMA related products relative to the TPH composite. However, there were higher amounts of ethoxylated bis-phenol A released from the TPH material. In terms of total mass of products released, human saliva demonstrated a greater ability to degrade Z250. In summary, HSDEA has been shown to contain esterase activities that can readily catalyze the biodegradation of current commercial composite resins.

Biological characterization of a novel biodegradable antimicrobial polymer synthesized with fluoroquinolones.

Biomaterial-related infections continue to represent a significant challenge to the medical community. Several approaches have been utilized to incorporate antimicrobial agents at the surface of implant devices in attempts to delay or eliminate the formation of biofilms. To date, most of these strategies have focused on drug conjugation or diffusion-limited systems for the delivery of such pharmaceutical agents. More recently, work has been presented on the feasibility of incorporating drugs into the backbone of polymers as a main-chain monomer. When sequenced into the backbone of the polymer with other monomers that are hydrolytically sensitive to enzyme-catalyzed breakdown, it is thought that drugs may be able to be selectively released. Specifically, degradable polyurethanes have been synthesized with fluoroquinolone antibiotics and have shown an ability to kill bacteria when released following degradation of the polymer chains by the macrophage-derived enzyme cholesterol esterase. However, specificity of the cleavage sites in the polymer was difficult to control. Since cholesterol esterase has specificity for hydrophobic moieties, it is desirable to alter the formulation of the polyurethanes to incorporate long hydrophobic monomers immediately adjacent to the ciprofloxacin molecule. Hence, the current study focuses on evaluating the enzyme-catalyzed degradation of a degradable polyurethane synthesized with 1,12 diisocyanatododecane as a substitute for 1,6 diisocyanatohexane, which was used in previous work. Validation of specific ciprofloxacin release and the generation of antimicrobial are shown. A preliminary cell study to assess the cytotoxicity of this biodegradable antibiotic polymer shows that the material has no observable effects on cell proliferation or cell membrane structure.

Scan reproducibility of magnetic resonance imaging assessment of aortic atherosclerosis burden.

Subclinical atherosclerosis precedes the onset of clinical disease by many years. Noninvasive magnetic resonance imaging (MRI) offers the opportunity to visualize and quantify atherosclerotic plaque. However, the reproducibility of MRI measurements of abdominal and thoracic aortic atherosclerosis has not been reported. Electrocardiogram-gated, T2-weighted, turbo spin echo MRI of the descending thoracic and abdominal aorta was performed on 16 subjects, comprising 10 subjects with multivessel coronary artery disease (CAD) and 6 subjects without angiographic CAD. Three identical MRIs were performed on each subject, with subject repositioning between the second and third scans. Aortic anatomic and plaque measurements were performed in a blinded fashion. Fourteen subjects (88%) had MRI evidence of atherosclerotic plaque on at least one image. Slice plaque burden, plaque area, and plaque perimeter were greater in the CAD group (52% vs. 9%, p = 0.002; 264 vs. 18 mm2, p = 0.009; 159 vs. 15 mm, p = 0.006, respectively). Measurements of total aortic lumen area, lumen circumference, plaque area, and plaque perimeter correlated highly among the three scans (all r = 0.96, all p < 0.001). Measurements of slice-specific aortic lumen area and lumen circumference also correlated highly (all r = 0.98, all p < 0.001). Correlations of slice-specific plaque area and plaque perimeter were significant (all p < 0.001) but less robust (r = 0.62-0.85). These data demonstrate that MRI is a reproducible technique for assessing aortic anatomy and total aortic atherosclerosis, but increased slice density should be considered if serial evaluation of slice-specific data is desired.

Centric ordering is superior to gradient moment nulling for motion artifact reduction in EPI.

Echo-planar imaging (EPI) is sensitive to motion despite its rapid data acquisition rate. Compared with traditional imaging techniques, it is more sensitive to motion or flow in the phase-encode direction, which can cause image artifacts such as ghosting, misregistration, and loss of spatial resolution. Consequently, EPI of dynamic structures (eg, the cardiovascular system) could benefit from methods that eliminate these artifacts. In this paper, two methods of artifact reduction for motion in the phase-encode direction are evaluated. First, the k-space trajectory is evaluated by comparing centric with top-down ordered sequences. Next, velocity gradient moment nulling (GMN) of the phase-encode direction is evaluated for each trajectory. Computer simulations and experiments in flow phantoms and rabbits in vivo show that uncompensated centric ordering produces the highest image quality. This is probably due to a shorter readout duration, which reduces T2* relaxation losses and off-resonance effects, and to the linear geometry of phantoms and vessels, which can obscure centric blurring artifacts.

A method to improve the B0 homogeneity of the heart in vivo.

A homogeneous static (B0) magnetic field is required for many NMR experiments such as echo planar imaging, localized spectroscopy, and spiral scan imaging. Although semi-automated techniques have been described to improve the B0 field homogeneity, none has been applied to the in vivo heart. The acquisition of cardiac field maps is complicated by motion, blood flow, and chemical shift artifact from epicardial fat. To overcome these problems, an ungated three-dimensional (3D) chemical shift image (CSI) was collected to generate a time and motion-averaged B0 field map. B0 heterogeneity in the heart was minimized by using a previous algorithm that solves for the optimal shim coil currents for an input field map, using up to third-order current-bounded shims (1). The method improved the B0 homogenelty of the heart in all 11 normal volunteers studied. After application of the algorithm to the unshimmed cardiac field maps, the standard deviation of proton frequency decreased by 43%, the magnitude 1H spectral linewidth decreased by 24%, and the peak-peak gradient decreased by 35%. Simulations of the high-order (second- and third-order) shims in B0 field correction of the heart show that high order shims are important, resulting for nearly half of the improvement in homogeneity for several subjects. The T2* of the left ventricular anterior wall before and after field correction was determined at 4.0 Tesis. Finally, results show that cardiac shimming is of benefit in cardiac 31P NMR spectroscopy and cardiac echo planar imaging.

The evaluation of dielectric resonators containing H2O or D2O as RF coils for high-field MR imaging and spectroscopy.

Electromagnetic resonators consisting of low-loss dielectric material and/or metallic boundaries are widely used in microwave technologies. These dielectric resonators usually have high Q factors and well-defined field distributions. Magnetic resonance imaging was shown as a way of visualizing the magnetic field distribution of the resonant modes of these resonators, if the dielectric body contains NMR sensitive nuclei. Dielectric resonators have also been proposed as RF coils for magnetic resonance experiments. The feasibility of this idea in high-field MR is discussed here. Specifically, the dielectric resonances of cylindrical water columns were characterized at 170.7 MHz (4 T 1H Larmor frequency), and evaluated as NMR transmit and receive coils. The dielectric resonance of a cylindrical volume of D2O was used to image a hand at 170.7 MHz. This study demonstrated that MRI is an effective way of visualizing the magnetic field in dielectric structures such as a water cylinder, and can potentially be generalized to solid-state dielectric devices. The possible applications of dielectric resonators other than simple cylindrical volumes in MRI and MR solution spectroscopy at high field strengths are also discussed.

An in vivo automated shimming method taking into account shim current constraints.

Many in vivo imaging techniques require magnetic field homogeneity in the volume of interest. Shim coils of the second and third order spherical harmonics have been used successfully to compensate for complicated field variations caused by the human anatomy itself. The available currents of these coils are invariably limited. In this note we demonstrate that these limits significantly affect the optimal shim condition. We propose an automated in vivo shimming method for arbitrary volumes of interest using 3-dimensional (3D) field maps. This method is a modification of previous works using least-squares criteria. The main difference is that a constrained optimization is performed in vivo under the current limits of the shim coils, which improved the field homogeneity significantly over simple truncations of the least-squares solutions. This shimming method was used with head scans of five normal volunteers on a 4.0 tesla scanner. A fast double-echo sequence was used to obtain field maps, and a new field uniformity measure was derived for this method. The field mapping sequence was tested against a standard single-echo Dixon sequence used by previous investigators, and the stability of the shimming method was tested by repeated studies on the same subject.

Radiofrequency shielding of surface coils at 4.0 T.

Because radiation loss associated with a radiofrequency (RF) coil increases as roughly the fourth power of the frequency, this loss mechanism may become important in high-field studies above 2.0 T. In this study, the contribution of radiation losses at 4.0 T were determined in a rectangular surface coil using an RF shield to modify the radiation losses. The effect of this shield was determined on coil Q, B1 distribution, and signal to noise as a function of distance between the coil and the shield. Phantoms and human tissue were evaluated to characterize the loss mechanisms. The results demonstrate a large radiation loss in the unshielded surface coil. However, the radiation losses in vivo were not dominant owing to a large inductive loss occurring from dielectric currents in the body at 170 MHz.

Musculoskeletal MR imaging at 4 T and at 1.5 T: comparison of relaxation times and image contrast.

PURPOSE: To evaluate the relaxation time-based contrast between the main tissues of the musculoskeletal system as measured in the human knee with magnetic resonance imaging at 4 T and 1.5 T. MATERIALS AND METHODS: Five volunteers underwent 4-T and 1.5-T imaging. Inversion-recovery series were used to measure T1 values, and T2 values were measured with a spin-echo sequence. RESULTS: T1 values increased in all tissues with 4-T imaging. Values increased in muscle from 1 to 1.8 seconds, in fat from 0.3 to 0.4 seconds, and in cartilage from 0.8 to 1.5 seconds. T2 values were 10%-20% shorter in all tissues at 4 T. CONCLUSION: Advantages of 4-T imaging compared with 1.5-T imaging include a higher signal-to-noise ratio and an improved signal difference-to-noise ratio. However, any improvement in signal-to-noise ratio at high field strengths can partially be reduced by the increase in the T1 value. The slightly shorter T2 values at 4 T do not affect image contrast.

Actions of platelet-derived growth factor isoforms in mesangial cells.

Platelet-derived growth factor (PDGF) occurs as homodimers or heterodimers of related polypeptide chains PDGF-BB, -AA, and -AB. There are two receptors that bind PDGF, termed alpha and beta. The beta receptor recognizes PDGF B chain and is dimerized in response to PDGF BB. The alpha receptor recognizes PDGF B as well as A chains and can be dimerized by the three dimeric forms of PDGF AA, AB, and BB. To characterize PDGF receptor signaling mechanisms and biologic activities in human mesangial cells (MC), we explored the effects of the three PDGF isoforms on DNA synthesis, phospholipase C activation, and PDGF protooncogene induction. PDGF-BB homodimer and AB heterodimer induced a marked increase in DNA synthesis, activation of phospholipase C, and autoinduction of PDGF A and B chain mRNAs, whereas PDGF-AA homodimer was without effect. The lack of response to PDGF AA could be accounted for by down-regulation of the PDGF-alpha receptor since preincubation of MC with suramin restored PDGF AA-induced DNA synthesis. Ligand binding studies demonstrate specific binding of labeled PDGF BB and AB and to a lower extent PDGF AA isoforms to mesangial cells. These results are consistent with predominant expression of PDGF beta receptor in MC, which is linked to phospholipase-C activation. The potent biologic effects of PDGF-AB heterodimer in cells that express very few alpha receptors and do not respond to PDGF AA are somewhat inconsistent with the currently accepted model of PDGF receptor interaction and suggest the presence of additional mechanisms for PDGF isoform binding and activation.

Endothelin stimulates PDGF secretion in cultured human mesangial cells.

Endothelin, a 17-DKa peptide originally described as a potent vasoconstrictor, also stimulates the release of important regulators of glomerular hemodynamics such as atrial natriuretic factor and renin. In the present study we investigated the role of endothelin in the release of another potent vasoconstrictor and mitogen of human mesangial cells, the platelet-derived growth factor. Endothelin stimulated PDGF release at 12 hours and the effect was sustained for 36 hours. This effect was associated with the enhanced induction of mRNAs encoding PDGF A- and B-chain. Endothelin also induced mitogenesis in human mesangial cells which was accompanied by activation of phospholipase C with increased inositol phosphate turnover. These data suggest a mechanism by which endothelin may regulate mesangial cell function in disease states.

Phosphatidic acid modulates DNA synthesis, phospholipase C, and platelet-derived growth factor mRNAs in cultured mesangial cells. Role of protein kinase C.

Increases in cell phosphatidic acid content occur in response to a wide variety of agonists, many of which have growth promoting properties. These changes have correlated with calcium flux, enzyme activation, gene induction, or cell proliferation. In the current studies we show that exogenous phosphatidic acid (PA) and phosphatidylserine stimulate phosphoinositide hydrolysis and DNA synthesis in cultured human renal mesangial cells. These phospholipids also induce mRNAs for platelet-derived growth factor (PDGF). The activation of phospholipase C by PA appears to be desensitized via protein kinase C as brief preincubation with phorbol ester abrogates the effect. PA-induced DNA synthesis is only partly mediated via protein kinase C as co-incubation with the inhibitor staurosporine blunts DNA synthesis by only one-third. In contrast, induction of PDGF A-chain mRNA is almost totally inhibited by staurosporine. We propose that changes in endogenous phospholipids such as PA or phosphatidylserine may serve as common signaling pathway for a variety of growth factors. Induction of PDGF proto-oncogenes via protein kinase C may represent one mechanism by which this cell activation occurs.

Regulation of mesangial cell growth by polypeptide mitogens. Inhibitory role of transforming growth factor beta.

Proliferation of mesangial cells is a common histologic abnormality in glomerular diseases. In vivo studies suggest a role for platelets and monocytes-macrophages in mediating glomerular hypercellularity. The authors recently reported that several peptide growth factors stimulate DNA synthesis and growth of human mesangial cells. This article reports that transforming growth factor beta (TGF-beta), a peptide released by inflammatory cells and platelets, inhibits DNA synthesis and growth of human mesangial cells. The stimulatory and inhibitory effects of these mitogens on DNA synthesis and growth was confirmed by autoradiography and cell counting. The inhibitory effect of TGF-beta is not mediated at the receptor level because TGF-beta did not inhibit the binding of epidermal growth factor (EGF) or platelet-derived growth factor (PDGF) to mesangial cells. Because peptide growth factors that stimulate DNA synthesis in mesangial cells induce expression of PDGF mRNAs, the effect of TGF-beta on PDGF mRNAs expression induced by peptide growth factors was studied. TGF-beta did not lower the increased levels of PDGF mRNAs caused by EGF or PDGF. These data show that TGF-beta is a potent inhibitor of DNA synthesis and growth of mesangial cells. The mechanism of the inhibitory effect of TGF-beta remains to be determined.

Platelet-derived growth factor synthesis in mesangial cells: induction by multiple peptide mitogens.

Platelet-derived growth factor (PDGF) has been implicated in several nonmalignant pathophysiological processes, including proliferative diseases of the kidney. Glomerular mesangial cells secrete a PDGF-like factor and express the PDGF A-chain and c-sis (or B-chain) mRNAs. We report here that both mRNAs are induced by serum and this effect can be mimicked by recombinant PDGF, which also markedly stimulates DNA synthesis. Other growth factors, such as epidermal growth factor (EGF), transforming growth factor type alpha, basic fibroblast growth factor (bFGF), and tumor necrosis factor type alpha (TNF-alpha) also are mitogenic for human mesangial cells and induce expression of the PDGF mRNAs. EGF, TNF-alpha, and bFGF also stimulate these cells to secrete a PDGF-like factor. Furthermore, anti-PDGF antibody partially abrogates the mitogenic effect of EGF, suggesting that mitogen-stimulated PDGF synthesis in mesangial cells is at least partly responsible for cell growth induced by other growth factors. In contrast to these results, transforming growth factor type beta (TGF-beta), while inducing both mRNAs, is not mitogenic, indicating that its effect on message levels can be dissociated from DNA synthesis. These data suggest that several peptide growth factors regulate the growth of mesangial cells and that PDGF may be an effector molecule that plays a role in the mitogenic response to many of these growth stimuli.

Massive resection and allograft transplantation in the treatment of malignant bone tumors.

Nineteen massive resections and allograft transplantations have been performed for malignant or aggressive bone tumors. Allograft procurment technic uses freezing of the segment to decrease immunogenicity of the bony portion and glycinerization of the cartilage to maintain chondrocyte viability during freezing and thawing. Fifteen Fifteen of the patients have been followed for an average of almost two years and were evaluated for early results by serial follow-up studies, including clinical, laboratoy, x-ray and scan data. Despite numerous complications (related to both tumor and operation) none have metastases, local recurrence, or major functional impairment except for two whose grafts became infected. We conclude that, although still experimental, allograft replacement may in the future serve as an important approach to certain neoplastic conditions of bones and joints.

Interpretation of roentgenograms via interactive television.

The diagnostic quality of roentgenographic images transmitted by interactive television was evaluated. A series of 100 kidney, ureter and bladder, chest, and bone radiographs were read individually by five radiologists, both on direct viewing and on viewing a monitor image of the television signal. The latter was transmitted by microwave a distance of 28 miles, including four transmission legs. Analysis in terms of receiver operating characteristic curves and critical tables indicated that the television interpretations were of acceptable accuracy, in view of the participants' inexperience with teleradiology.