Fractional flow reserve at 2013: an update.

Fractional flow reserve (FFR) has become an extremely valuable tool for assessing the hemodynamic significance of intermediate coronary lesions in patients with stable coronary syndromes. This manuscript delineates the current data supporting FFR use to guide cardiovascular interventions in comparison to other invasive and non-invasive modalities. The correlation between FFR, symptom severity and likelihood of future major cardiovascular events are critically examined in view of the FAME-2 study results. The authors delineate the scientific gaps, potential pitfalls and misconceptions related to FFR with regards to current and emerging indications. Described are the most important developments related to FFR in 2012: instantaneous wave free ratio and non-invasive CT angiography based FFR. The manuscript proposes areas of future research to enhance the scientific data supporting current FFR clinical algorithms and strategies.

Fractional flow reserve (FFR): changing the practice of interventional cardiology.

Fractional flow reserve (FFR) has become an extremely valuable tool for assessing the hemodynamic significance of intermediate coronary lesions. This manuscript delineates the current guidelines regarding the use of FFR and discusses emerging indications for the use of this diagnostic tool and how they compare with and complement non-invasive or other invasive diagnostic modalities. The manuscript addresses some of the key unanswered questions related to FFR, the potential pitfalls of this tool and discusses future directions of use and research.

Tunnel magnetoresistance for coherent spin-flip processes on an interacting quantum dot.

Spin-polarized electronic tunneling through a quantum dot coupled to ferromagnetic electrodes is investigated within a nonequilibrium Green function approach. An interplay between coherent intradot spin-flip transitions, tunneling processes and Coulomb correlations on the dot is studied for current-voltage characteristics of the tunneling junction in parallel and antiparallel magnetic configurations of the leads. It is found that due to the spin-flip processes electric current in the antiparallel configuration tends to the current characteristics in the parallel configuration, thus giving rise to suppression of the tunnel magnetoresistance (TMR) between the threshold bias voltages at which the dot energy level becomes active in tunneling. Also, the effect of a negative differential conductance in symmetrical junctions, splitting of the conductance peaks, significant modulation of TMR peaks around the threshold bias voltages as well as suppression of the diode-like behavior in asymmetrical junctions is discussed in the context of coherent intradot spin-flip transitions. It is also shown that TMR may be inverted at selected gate voltages, which qualitatively reproduces the TMR behavior predicted recently for temperatures in the Kondo regime, and observed experimentally beyond the Kondo regime for a semiconductor InAs quantum dot coupled to nickel electrodes.

Phonon-assisted spin-polarized tunneling through an interacting quantum dot.

Using the nonequilibrium Green function technique we study theoretically spin-polarized transport in double-barrier tunneling junctions based on a single-level quantum dot interacting with a local phonon mode. Phonon emission and absorption spectra have been calculated for arbitrary Coulomb correlations on the dot and for different temperatures. It is shown that in the nonlinear response regime the electron-phonon interaction gives rise to current suppression in symmetric junctions as well as to oscillations of the tunnel magnetoresistance (TMR). In asymmetric junctions, the same mechanism may lead effectively to enhancement of the diode-like characteristics. We have also found that at sufficiently low temperatures additional phonon-induced resonance peaks appear in the linear spectral function on both sides of the main resonance peaks corresponding to the quantum dot energy levels. The case of negative effective charging energy is also analyzed numerically. A significant enhancement of electric current (or suppression of TMR) above the threshold bias voltages at which the dot energy level enters the tunneling window is observed. The gate voltage-controlled rectification effect of the tunneling current in asymmetric junctions with positive and negative effective Coulomb correlations is also discussed.

Angle-corrected imaging transcranial doppler sonography versus imaging and nonimaging transcranial doppler sonography in children with sickle cell disease.

BACKGROUND AND PURPOSE: Nonimaging transcranial Doppler sonography (TCD) and imaging TCD (TCDI) are used for determination of the risk of stroke in children with sickle cell disease (SCD). The purpose was to compare angle-corrected, uncorrected TCDI, and TCD blood flow velocities in children with SCD. MATERIALS AND METHODS: A total of 37 children (mean age, 7.8 +/- 3.0 years) without intracranial arterial narrowing determined with MR angiography, were studied with use of TCD and TCDI at the same session. Depth of insonation and TCDI mean velocities with and without correction for the angle of insonation in the terminal internal carotid artery (ICA) and middle (MCA), anterior (ACA), and posterior (PCA) cerebral arteries were compared with TCD velocities with use of a paired t test. RESULTS: Two arteries were not found on TCDI compared with 15 not found on TCD. Average angle of insonation in the MCA, ACA, ICA, and PCA was 31 degrees , 44 degrees , 25 degrees , and 29 degrees , respectively. TCDI and TCD mean depth of insonation for all arteries did not differ significantly; however, individual differences varied substantially. TCDI velocities were significantly lower than TCD velocities, respectively, for the right and left sides (mean +/- SD): MCA, 106 +/- 22 cm/s and 111 +/- 33 cm/s versus 130 +/- 19 cm/s and 134 +/- 26 cm/s; ICA, 90 +/- 14 cm/s and 98 +/- 27 cm/s versus 117 +/- 18 cm/s and 119 +/- 23 cm/s; ACA, 74 +/- 24 cm/s and 88 +/- 25 cm/s versus 105 +/- 23 cm/s and 105 +/- 31 cm/s; and PCA, 84 +/- 27 cm/s and 82 +/- 21 cm/s versus 95 +/- 23 cm/s and 94 +/- 20 cm/s. TCD and angle-corrected TCDI velocities were not statistically different except for higher angle-corrected TCDI values in the left ACA and right PCA. CONCLUSION: TCD velocities are significantly higher than TCDI velocities but are not different from the angle-corrected TCDI velocities. TCDI identifies the major intracranial arteries more effectively than TCD.

Fractional flow reserve and instantaneous wave free ratio in 2015.

In the recent years it has become apparent that angiography-based assessment of coronary artery stenosis suffers from considerable inaccuracy and pitfalls. Besides interobserver variability in assessing stenosis severity, the correlation between angiographic severity and ischemia is suboptimal. Percutaneous coronary intervention (PCI) guided by the physiologic lesion assessment employing fractional flow reserve (FFR) is rendered superior to angiographic lesion assessment and proven to improve cardiovascular outcomes and reduce cost. In this manuscript we discuss the accepted and emerging clinical indications for FFR use. The correlation between FFR and symptoms, stress imaging and intravascular ultrasound are reviewed along with the inherent limitations and pitfalls of these diagnostic technologies. The data regarding the correlation between Instantaneous (vasodilator free) wave-free ratio (iFR) and conventional FFR is summarized.

Advanced therapeutic options in pulmonary hypertension: who, what and when?

Pulmonary hypertension (PH) is the common hemodynamic consequence of various pathophysiologic mechanisms. Since the publication of the most current American and European guidelines (2009) new agents were introduced into the clinical arena while data regarding former drugs has been substantiated. The therapeutic endeavor of evaluating new therapies for PH targets patients based on their PH type and symptom severity with the hope to demonstrate hemodynamic and functional benefits along with reduction in morbidity and mortality. Although patients' outcomes (predominantly among type I and IV) have improved, the hemodynamic and symptomatic benefit is modest and not uniform. The purpose of this review is to objectively assess the benefits of the currently available dedicated agents. It is our hope that with early detection and careful individual titration of new combination therapy in expert hands, we will better serve a larger proportion of our PH patients.

Biodegradable polymeric nanoparticles as drug delivery devices.

This review presents the most outstanding contributions in the field of biodegradable polymeric nanoparticles used as drug delivery systems. Methods of preparation, drug loading and drug release are covered. The most important findings on surface modification methods as well as surface characterization are covered from 1990 through mid-2000.

On the applicability of Arrhenius plot methods to determine surface energetic heterogeneity of adsorbents and catalysts surfaces from experimental TPD spectra.

Recovering adsorption energy distribution from experimental data belongs to most difficult problems of adsorption science. In the case when thermodesorption data are used as a source of information, that difficult problem is overcome by the common use of the Arrhenius plot methods. So, we decided to carry out an extensive model investigation to show, how reliable information concerning the surface energetic heterogeneity is obtained by using the Arrhenius plot methods. Like in our previous publications we have used the Statistical Rate Theory of Interfacial Transport to describe the adsorption/desorption kinetics. Our model investigations showed, that the Arrhenius plot methods, cannot provide reliable information about the surface energetic heterogeneity. Moreover, for strongly heterogeneous surfaces a linear relationship exists between the logarithm of the pre-exponential constant and the adsorption energy, for certain adsorption coverages. That kind of compensation effect has, so far, been ascribed to interactions between the adsorbed molecules. The failure of the popular Arrhenius plot method puts, as an urgent agenda, the development of reliable methods for recovering adsorption energy distribution from the thermodesorption data.

Calorimetric effects accompanying ion adsorption at the charged metal oxide/electrolyte interfaces: effects of the correlations between the binding-to-surface energies of various surface complexes.

As has been shown in our earlier publications, a theoretical description of ion adsorption at the real, energetically heterogeneous oxide/electrolyte interfaces, involves necessary assumption about the correlations between the adsorption energies of the various surface complexes formed at this interface. So far, only two extreme models have been considered in such theoretical descriptions: one model assuming that high correlations exist, and the other assuming that practically no correlations exist. The purpose of this paper is to develop yet another description based on a model assuming that some partial correlations exist between the adsorption energies of the various surface complexes. The other purpose of this publication is to test these three models by analysing some experimental data reported so far in literature. Such data sets must include necessary information about the enthalpic effects accompanying ion adsorption. This is because enthalpic effects are known to be more sensitive to the mechanistic models underlying a theoretical description of adsorption systems. With such requirements in mind, we have selected three adsorption systems: Al2O3/NaCl, TiO2/NaCl and silica/NaCl, for our analysis. Our theoretical-numerical analysis of the behaviour of these adsorption systems suggests that either none or partial correlations exist between the adsorption energies of the various surface complexes. However, that analysis also shows, that the present accuracy of the experimental data does not allow us to draw more elaborate conclusions.

The Raman spectra of selenomethionine and selenocystine.

The trace element selenium is known to be a part of the enzyme glutathione peroxidase (glutathione-hydrogen peroxide oxidoreductase, E.C.1.11.1.9). Studies have shown that selenium in the enzyme exists in at least two forms or oxidation states. It is probable that selenium has been incorporated into the enzyme as the selenocysteine amino acid. In the present study, the Raman spectra of selenocystine and selenomethionine have been obtained, structural assignments have been verified, and the behavior of the two selenoamino acids have been monitored under varying conditions of oxidative stress. The assignments will assist in the interpretation of the spectrum of the actual enzyme.

In-vitro release kinetics of cefadroxil-loaded sodium alginate interpenetrating network beads.

This paper reports the development of new interpenetrating polymeric networks of sodium alginate with gelatin or egg albumin cross-linked with a common cross-linking agent, glutaraldehyde, for the in-vitro release of cefadroxil. The beads formed were characterized by Fourier transform infra-red spectroscopy, scanning electron microscopy and differential scanning calorimetry. Swelling/drying experiments were performed to compute the diffusion coefficients and the molecular mass between cross-links of the beads. The release results were evaluated using an empirical equation to understand the transport mechanism. The extent of cross-linking was studied in terms of the size and release characteristics of the beads. The experimental and derived quantities have been used to study their dependencies on the nature of the polymeric beads, transport mechanism, encapsulation efficiency and drug diffusion, as well as the cross-linking abilities of the polymers.

[Transcranial color-coded Doppler sonography: getting started]. / Przezczaszkowa ultrasonografia dopplerowska z obrazowaniem w kolorze: podstawy metodologii badania.

Transcranial color Doppler sonography, in contrary to conventional transcranial Doppler ultrasound, allows outlining of the parenchymal structures and visualization of the vessel examined. Angle-corrected blood velocities can be obtained which are closer to in-situ values. In this educational assay, we demonstrate cerebral vascular anatomy using 3-D MR angiographic images of the major cerebral arteries to show their relationship to neighboring structures, the acoustic window, and the ultrasound beam. We describe principles of the examination, and discuss the different types of physiological flow velocity spectra. We show how to identify with color Doppler ultrasonography the main intracranial arterial trunks, and how to avoid pitfalls caused by anatomic variability of their course and location. We draw attention on significant age and sex dependency of blood flow parameters which makes standardization of obtained transcranial Doppler results indispensable for clinical valuable concluding.

Cerebrovascular reactivity across the menstrual cycle in young healthy women.

This study evaluated the relationship of cerebrovascular reactivity in young healthy women with changes in concentrations of circulating ovarian hormones throughout the menstrual cycle. Nineteen healthy nulliparous, right-handed, regularly menstruating women (age 23-25 years) underwent color-coded duplex sonography of the common (CCA), internal (ICA) and external (ECA) carotid arteries on both sides. Mean blood flow velocity values measured before and ten minutes after intravenous administration of 1000 mg acetazolamide (ACE) were assessed in relation to the serum concentration of estrogen and progesterone on days 5, 13 and 26 of the cycle. After ACE administration flow velocity in the right CCA and ICA increased by 23% and 35% on day 5, 12% and 31% on day 13 and 30% and 47% on day 26 respectively, and the changes were significantly larger on the right side (F=6.793 and F=4.098 respectively; both p<0.05). Changes in blood flow velocity in the right CCA and ICA after ACE injection were significantly associated with ovarian hormone concentrations (F=3.828, P=0.028 and F=3.671, P=0.032 respectively). We conclude that cerebrovascular reactivity changes across the menstrual cycle are associated with ovarian steroid hormone changes, and are asymmetric. The results imply that vasculature of the right hemisphere may undergo cyclic vasodilation across the menstrual cycle and this effect should be considered in studies of cerebrovascular reactivity in women with migraine and mood disorders.

Kinetic adsorption energy distributions of rough surfaces: a computational study.

The adsorption energy distribution usually refers to localized monolayers of adsorbate at thermodynamic equilibrium. Many papers have been published that analyze its influence on adsorption isotherms, heats of adsorption, and adsorption kinetics. However, the adsorption energy distribution, in its classical thermodynamic equilibrium sense, may be not as useful as expected. This is because many important processes involving adsorption have dynamic character and reactant particles have a finite time for penetration of the adsorbent. The above suggests that some adsorption centers located in less accessible fragments of the surface can be invisible in a dynamic process. However, under conditions allowing the thermodynamic equilibrium such adsorption centers could noticeably contribute to the adsorption energy distribution. The aim of this work is to measure the adsorption energy distributions of special rough surfaces using a dynamic method. This method is based on the molecular dynamics simulation of an ideal gas flowing over a sample surface. The ideal gas particles penetrate the surface, and at the moment of collision of a gas particle with the surface the Lennard-Jones potential energy is calculated. This energy can be identified with the adsorption energy at a given point on the surface. The surfaces used in the calculations have been created using two surface growth models (i.e., random deposition and ballistic deposition). The application of these highly disordered surfaces enables us to draw some general conclusions about the properties of real surfaces that are usually far from any deterministic geometry.

Determination of hexamethylene diisocyanate-based isocyanates in spray-painting operations. Part 2. Comparison of high performance liquid chromatography with capillary zone electrophoresis.

A capillary zone electrophoresis (CZE) approach was developed for the determination of hexamethylene diisocyanate (HDI) monomer and HDI-based oligomers. A comparison of CZE with high performance liquid chromatography (HPLC) indicates that the CZE separation completely isolates isocyanates from excess solvent, derivatizing reagent and pigment while offering a fivefold increase in sensitivity. The CZE approach allows for the quantification of HDI monomer and oligomer within a 1 min time window under the run conditions selected. For the determination of HDI-based oligomer, provided that the relative response with respect to HDI monomer is calculated, there is no significant difference (p < 0.05, n = 10) in the isocyanate air concentration when using either HPLC or CZE. The results are significant because they indicate that CZE has advantages for the determination of both HDI-based oligomer and HDI monomer generated during spray-painting operations.

Evaluation of tryptamine in an impinger and on XAD-2 for the determination of hexamethylene-based isocyanates in spray-painting operations.

Tryptamine was evaluated as a reagent for derivatizing hexamethylene diisocyanate (HDI) monomer and oligomers during actual spray-painting operations. In one side-by-side sampling study, an impinger filled with 1-(2-methoxyphenyl)piperazine in toluene was compared with a second impinger filled with tryptamine in dimethyl sulfoxide (DMSO). The amount of HDI monomer obtained was below the limit of quantification for both impingers. The amount of HDI oligomer obtained when using 1-(2-methoxyphenyl)piperazine in toluene was comparable to the amount obtained when using an impinger filled with tryptamine in DMSO. In a second side-by-side sampling study, a tryptamine-coated XAD-2 resin was used as a sorbent. The relative collection efficiency of the tryptamine-coated XAD-2 resin was on average 60% of the value obtained using an impinger filled with tryptamine in DMSO. The results indicate that using an impinger filled with tryptamine in DMSO gives higher concentrations of isocyanate than a tryptamine-coated XAD-2 sorbent for HDI monomer and oligomer.

Determination of hexamethylene-based isocyanates in spray-painting operations. Part 1. Evaluation of a polyurethane foam sponge sampler.

A polyurethane foam (PUF) sponge was mounted in a cassette sampler and evaluated as a sorbent for the collection of hexamethylene diisocyanate (HDI) monomer and HDI-based oligomers. Recovery studies indicated 112 +/- 34% average recovery of HDI monomer and 92 +/- 9% and 97 +/- 25% average recovery of HDI-based oligomers when using impregnated PUF sponges. The PUF sponge was also evaluated during actual spray-painting operations. In a series of side-by-side sampling events, an impinger filled with 1-(2-methoxyphenyl)piperazine (MOP) in toluene was compared directly with a cassette sampler containing a PUF sponge impregnated with MOP or 1-(9-anthracenylmethyl)piperazine (MAP) in dimethyl sulfoxide (DMSO). For the analysis of HDI-based oligomer, there is no significant difference (p < 0.05, n = 7) in the air concentration when sampling with either the PUF sponge cassette or the impinger. The results are significant because they indicate that a PUF sponge, which is more convenient than an impinger, may be used for the collection of HDI-based oligomer generated during spray-painting operations.

Microspheres as floating drug-delivery systems to increase gastric retention of drugs.

Gastric emptying is a complex process, which is highly variable and makes in vivo performance of the drug-delivery systems uncertain. In order to avoid this variability, efforts have been made to increase the retention time of the drug-delivery systems for more than 12 h. The floating or hydrodynamically controlled drug-delivery systems are useful in such applications. The present review addresses briefly the physiology of the gastric emptying process with respect to floating drug-delivery systems. In recent years, the multiparticulate drug-delivery systems are used in the oral delivery of drugs. One of the approaches toward this goal is to develop the floating microspheres so as to increase the gastric retention time. Such systems have more advantages over the single-unit dosage forms. The development of floating microspheres involves different solvent evaporation techniques to create the hollow inner core. The present review addresses the preparation and characterization of the floating microspheres for the peroral route of administration of the drug.

A comparison of solid sampler methods for the determination of hexamethylene-based isocyanates in spray-painting operations.

A polyurethane foam sponge impregnated with 1-(2-methoxyphenyl) piperazine in dimethylsulfoxide was mounted in both cassette and inhalable organic monitor samplers and these were then compared with a dual-filter cassette. The samplers were used for the collection of hexamethylene diisocyanate (HDI) monomer and oligomers during actual spray-painting operations. The dual filter cassettes were positioned on a mannequin. The polyurethane foam cassette (PUF CAS) and polyurethane foam inhalable organic monitor (PUF IOM) samplers were positioned on a cart in the same maximum overspray area. Data from this pilot study suggest that there is no significant difference (P < 0.05, n = 6) in the amount of HDI monomer obtained with the PUF IOM sampler when compared with the amount obtained from the dual filter cassette. The data also suggest that the PUF IOM sampler yields a higher amount of HDI oligomer than either the dual filter cassette or the PUF CAS sampler, neither of which exhibited a significant difference (P < 0.05, n = 6) from each other.