Post-occlusional hyperemia for fractional flow reserve assessment and pull-back curve analysis.

Balloon occlusion is a potential method for inducing hyperemia to measure post-percutaneous coronary intervention (PCI) fractional flow reserve (FFR). The objective of this study was to determine the clinical usefulness of post-occlusional hyperemia. FFRs measured using post-occlusional hyperemia caused by 30 (FFRoccl30) and 60 s (FFRoccl60) of balloon occlusion after PCI were compared in 60 lesions from 60 patients. The duration of hyperemia was also measured. There was a strong correlation between FFRoccl30 and FFRoccl60 (r = 0.969, p < 0.01). The duration of hyperemia was significantly longer with FFRoccl60 than with FFRoccl30 (68 ± 23 vs. 37 ± 15 s, p < 0.01). The time required for pullback curve analysis was around 45 s. However, in 7 (12%) cases, the duration of hyperemia with FFRoccl60 was < 45 s, which was not enough for pull-back curve analysis. To predict the duration of hyperemia with FFRoccl60 ≥ 45 s, the receiver operating characteristic curve analysis revealed a cut-off value of 25 s of hyperemia with FFRoccl30. FFRoccl30 is sufficient for diagnostic purposes. FFRoccl60 is suitable for pull-back curve analysis in select cases based on predictions made using the duration of hyperemia with FFRoccl30.

Angiogram based fractional flow reserve in patients with dual/triple vessel coronary artery disease.

OBJECTIVE: To assess the performance of angiography derived Fractional Flow Reserve (FFRangio) in multivessel disease (MVD) patients undergoing angiography. BACKGROUND: FFR is the reference standard for physiologic assessment of coronary stenosis and guidance of revascularization, especially in patients with MVD, yet it remains grossly underutilized. The non-wire based FFRangio performs well in non-MVD patients, but its accuracy in MVD is unknown. METHODS: A prospective clinical study was conducted at Gifu Heart Centre, Japan. Patients underwent physiologic assessment of all relevant coronary lesions using wire-based FFR (wbFFR) and FFRangio. Primary outcome was diagnostic performance (sensitivity, specificity, accuracy) for FFRangio with wbFFR as reference. Other outcomes were the correlation between wbFFR/FFRangio, time required for wbFFR/FFRangio measurements, and the effect of wbFFR/FFRangio on the reclassification of coronary disease severity. RESULTS: Fifty patients (118 lesions in total) were included. Mean age was 72 ±â€¯9 years, 72% were male, 36% had triple vessel disease and the average SYNTAX score was 13. The mean measurement of wbFFR and FFRangio were 0.83 ±â€¯0.12 and 0.81 ±â€¯0.11, respectively. Accuracy, sensitivity and specificity for FFRangio were 92.3% (95% CI 79.1-98.4%), 92.4% (95% CI 84.3-97.2%) and 92.4% (95% CI 87.4-97.3%), respectively. Pearson's r between wbFFR and FFRangio was 0.83. FFRangio measurement was faster than wbFFR (9.6 ±â€¯3.4 vs. 15.0 ±â€¯8.9 min, p < 0.001). CONCLUSIONS: In patients with MVD, FFRangio shows good correlation and excellent diagnostic performance compared to wbFFR, and measuring FFRangio is faster than wbFFR. These results highlight the potential clinical benefits of utilizing FFRangio among patients with MVD.

Spontaneous Polarization and Bulk Photovoltaic Effect Driven by Polar Discontinuity in LaFeO_{3}/SrTiO_{3} Heterojunctions.

Structurally coherent and chemically abrupt interfaces formed between polar and nonpolar perovskite oxides provide an ideal platform for examining the purely electronic reconstruction known as the polar catastrophe and the emergence of mobile or bound charges at the interface. The appearance of mobile charges induced by the polar catastrophe is already established in the LaAlO_{3}/SrTiO_{3} heterojunctions. Although not experimentally verified, the polar catastrophe can also lead to the emergence of spontaneous polarization. We report that thin films of originally nonpolar LaFeO_{3} grown on SrTiO_{3} are converted to polar as a consequence of the polar catastrophe. The induced spontaneous polarization evokes photovoltaic properties distinct from conventional p-n junctions, such as a switching of the photocurrent direction by changing the interfacial atomic sequence. The control of the bulk polarization by engineering the interface demonstrated here will expand the possibilities for designing and realizing new polar materials with photovoltaic functions.

Large anisotropic deformation of skyrmions in strained crystal.

Mechanical control of magnetism is an important and promising approach in spintronics. To date, strain control has mostly been demonstrated in ferromagnetic structures by exploiting a change in magnetocrystalline anisotropy. It would be desirable to achieve large strain effects on magnetic nanostructures. Here, using in situ Lorentz transmission electron microscopy, we demonstrate that anisotropic strain as small as 0.3% in a chiral magnet of FeGe induces very large deformations in magnetic skyrmions, as well as distortions of the skyrmion crystal lattice on the order of 20%. Skyrmions are stabilized by the Dzyaloshinskii-Moriya interaction, originating from a chiral crystal structure. Our results show that the change in the modulation of the strength of this interaction is amplified by two orders of magnitude with respect to changes in the crystal lattice due to an applied strain. Our findings may provide a mechanism to achieve strain control of topological magnetic structures based on the Dzyaloshinskii-Moriya interaction.

Magnetization amplified by structural disorder within nanometre-scale interface region.

Direct magnetization measurements from narrow, complex-shaped antiphase boundaries (APBs; that is, planar defect produced in any ordered crystals) are vitally important for advances in materials science and engineering. However, in-depth examination of APBs has been hampered by the lack of experimental tools. Here, based on electron microscopy observations, we report the unusual relationship between APBs and ferromagnetic spin order in Fe70Al30. Thermally induced APBs show a finite width (2-3 nm), within which significant atomic disordering occurs. Electron holography studies revealed an unexpectedly large magnetic flux density at the APBs, amplified by approximately 60% (at 293 K) compared with the matrix value. At elevated temperatures, the specimens showed a peculiar spin texture wherein the ferromagnetic phase was confined within the APB region. These observations demonstrate ferromagnetism stabilized by structural disorder within APBs, which is in direct contrast to the traditional understanding. The results accordingly provide rich conceptual insights for engineering APB-induced phenomena.

Pleomorphic adenoma in the lung.

Pleomorphic adenoma arising from right middle lobe bronchus is reported in an 18-year-old female. Right middle lobectomy was performed and the histologic pattern of the resected tumor was indistinguishable from that commonly described for pleomorphic adenoma of the salivary glands. Mitotic figures were not present. There has been no recurrence two years following surgery.

[Early replacement of intravenous aminophylline administration with oral theophylline in treating acute exacerbation of asthma].

Intravenous (i.v.) administration of aminophylline has been used to relieve acute exacerbation of bronchial asthma for almost a century. Despite confidence in its effectiveness, controversy has arisen about its efficacy. We currently use aminophylline in the routine treatment of asthma since the drug is essentially useful. Continuous aminophylline infusion tends to be used rather haphazardly in hospital wards, and the criteria for termination of an infusion have not been clarified. We therefore attempted to determine: 1) whether continuous aminophylline infusion is actually beneficial, 2) whether the TDM (treatment drug monitoring) system can be used to establish a protocol for prescribed dosing after an early switch from i.v. to oral administration, and 3) whether adherence to the protocol would contribute to decreases in the duration of hospitalization and in medical expenses. Seventeen patients with acutely exacerbated asthma were enrolled in this study. Nine patients were prescribed oral theophylline on the second hospital day (p.o. group), while eight received continuous i.v. aminophylline (i.v. group). The serum theophylline concentrations were maintained in the therapeutic range in both groups. Peak flow, symptom scores, and QOL scores showed significant improvements in the p.o. group on the third hospital day. It might therefore be possible, by using the TDM system, to set the dosage of theophylline so that hospitalization is shortened.

Reversal of airflow obstruction and improvement in cystic lesions with treatment of HIV associated PCP.

A 54-year-old Japanese male smoker in whom lung function had been normal developed airflow obstruction coincident with the development of human immunodeficiency virus (HIV)-associated Peumocystis carinii pneumonia (PCP). Chest high resolution computed tomography (HRCT) revealed cystic lesions involving the upper lung fields. Both cystic lesions and airflow obstruction improved simultaneously with treatment of PCP and acquired immunodeficiency syndrome (AIDS). Bronchiolar PCP lesions creating a check-valve mechanism may explain these reversible changes.

Applicability of Hyland's Living with Asthma Questionnaire for Japanese asthmatic patients.

OBJECTIVE: To assess the applicability of Hyland's Living with Asthma Questionnaire (LWAQ, 1991), one of the international health-related quality of life scales, for Japanese asthmatic patients with reference to its reproducibility and validity. SUBJECTS AND METHODS: The LWAQ was given to randomly selected asthmatic patients on two occasions separated by a 12-week interval. RESULTS: The mean scale score in the first study (n=304) was 1.83 (range, 1.14-2.77) and logarithmic values of the scores approached normal distribution. The scale scores in the first and second (n=158) studies were well correlated (r=0.81), however, the mean score decreased (0.08) significantly. The questions were further separated into 11 domains. The sex-domain was notable for a low response rate (68%), and scale scores in the sleep-, colds- and sex-domains in the first study varied considerably from those of the other domains. Frequency distributions of scores in the five constructs (Hyland 1996) were not normal and, with the exception of the colds construct, the relations among the remaining four constructs were similar to those previously reported (Hyland 1996). CONCLUSION: Analysis using the mean scale score, domain and construct in the LWAQ is applicable to Japanese asthmatic patients.

Increased production of nitrotyrosine in lung tissue of rats with radiation-induced acute lung injury.

The purposes of this study were 1) to identify the nitric oxide (NO) synthase (NOS) isoform responsible for NO-mediated radiation-induced lung injury, 2) to examine the formation of nitrotyrosine, and 3) to see whether nitrotyrosine formation and lung injury are reduced by an inducible NOS (iNOS) inhibitor, aminoguanidine. The left hemithorax of rats was irradiated (20 Gy), and the degree of lung injury, the expression of NOS isoforms, and the formation of nitrotyrosine and superoxide were examined after 2 wk. iNOS mRNA was induced, and endothelial NOS mRNA was markedly increased in the irradiated lung. Nitrotyrosine was detected biochemically and immunohistochemically. Aminoguanidine prevented acute lung injury as indicated by decreased protein concentration and lactate dehydrogenase activity in bronchoalveolar lavage fluid and improved NMR parameters and histology. Furthermore, the formation of nitrotyrosine was significantly reduced in the aminoguanidine group. We conclude that iNOS induction is a major factor in radiation-induced lung injury and that nitrotyrosine formation may participate in the NO-induced pathogenesis.

[Peak inspiratory flow during a diskhaler use in subjects unfamiliar with dry powder devices].

Dry power steroid was firstly introduced in Japan in 1998. We measured peak inspiratory flow (PIF) through a Diskhaler in the following groups: well-trained medical representative (EX group, n = 5), respiratory physicians (RP group, n = 19) and non-medical staffs (NM group, n = 31) who were not familiar with Diskhaler, and asthmatic patients who had been briefly trained by a video movie (TP group, n = 93). When PIF was less than 50 l/m dry powders were frequently remained in the brister. The mean PIF in the EX group was 96.1 +/- 12.6 l/m (mean +/- SD). Since the relationship between the PIF and airway pressure (Paw) during Diskhaler use was expressed as PIF = 16.3 square root of Paw-1.19 (r = 0.97), we calculated PIF from Paw measured by a handy barometer made by ourselves. The mean PIF in RP group was 77.0 +/- 30.1 l/m, and 36.8% of the subjects developed inappropriate PIF (i.e., above 100 l/m or below 50 l/m). In NM group the mean PIF was 53.5 +/- 20.4 l/m which was significantly higher than RP group. In this group 54.8% of the subjects yielded inappropriate PIF. The mean PIF in TP group was 64.9 +/- 24.5 l/m which was significantly lower than that in RP group. Those who developed inappropriate PIF occupied 43.2% of the RP subjects. We concluded that a quantitative presentation of PIF in mandatory to achieve an effective use of Diskhaler.

Massive hemoptysis due to Mycobacterium fortuitum infection controlled with bronchial artery embolization - a case report.

We reported a case of first reported pulmonary infection due to Mycobacterium fortuitum (M. fortuitum) with massive hemoptysis, successfully treated by bronchial artery embolization (BAE). A 78-year-old male was admitted to our hospital complaining of massive hemoptysis. A biochemical examination and DNA/DNA hybridization revealed M. fortuitum in the culture of his sputum. He was treated by BAE, and antituberculous agents and levofloxacin. The patient remains well without recurrence more than one and a half years after the admission.

The importance of polymorphonuclear leukocytes in lipopolysaccharide-induced superoxide anion production and lung injury: ex vivo observation in rat lungs.

The purpose of this study is to determine if the polymorphonuclear leukocyte (PMN) is a major causative agent for lipopolysaccharide (LPS)-induced lung injury and responsible for the excess production of superoxide anion in the lung. We measured superoxide anion production from the lung and pulmonary capillary permeability in rats with and without PMN depletion. The superoxide anion production from the lung was measured using a purpose-built ex vivo chemiluminescence apparatus. Pulmonary capillary permeability was evaluated by the Evans blue dye extravasation method. PMN sequestration was determined by counting PMNs in histologic tissue specimens using microscopy. All rats received 3 mg/kg LPS intravenously. Examinations were undertaken at 2, 6, and 12 h after the LPS injection. The PMN-depleted group received cyclophosphamide 4 days before the LPS injection, which resulted in a PMN count of less than 200 cells/microliter. In rats without PMN depletion, Evans blue dye extravasation increased significantly at 12 h after the LPS injection; PMN sequestration increased at 2, 6, and 12 h after the LPS injection; and superoxide anion production increased at 6 h and remained elevated at 12 h after the LPS injection. The increased permeability, PMN sequestration, and superoxide anion production were not seen in the PMN-depleted group. The contribution of the xanthine/xanthine oxidase system and alveolar macrophages to the observed superoxide anion production was negligible. We conclude that, in rats, the PMN is a major causative agent in LPS-induced lung injury and is responsible for the excess production of superoxide anion in the lung.

Dependence of transverse relaxation time T2 of biologic tissues on the interpulse delay time in Carr-Purcell-Meiboom-Gill (CPMG) measurements.

To determine the transverse relaxation time (T2) of biological tissues in nuclear magnetic resonance measurements, the Carr-Purcell-Meiboom-Gill (CPMG) method has been recommended to avoid the effect of external magnetic field inhomogeneity on T2 values. However, a dependence of T2 on the interpulse delay time (IPDT) in the CPMG measurements has been shown for biological tissues. The present study examined the dependence of the T2 on IPDT for muscle, lung (passively collapsed or degassed), and brain tissues. It was found that the CPMG T2 of the lung was strongly dependent upon the IPDT, in contrast to muscle and brain tissues. The IPDT dependence of the CPMG T2 for lung tissue, which was lessened by degassing, was affected by the magnetic field inhomogeneity due to air-tissue interfaces, but not by the spin-locking effect, since the T2 measured by the Carr-Purcell-Freeman-Hill (CPFH) method did not show this dependence. These results should aid in the evaluation of T2 values for biological tissues measured under various conditions and by different techniques.

Rapid response to inhaled frusemide in severe acute asthma with hypercapnia.

We report 7 patients with severe acute asthma unresponsive to standard medication, including sympathomimetic agents, aminophylline and corticosteroids, who responded to inhaled frusemide. All were hypercapneic with a mean PaCO2 of 7.7 kPa (57.7 mm Hg) [range 6.2-8.8 kPa (46.2-66.3 mm Hg)]. Following nebulization of 20 mg frusemide, clinical response was rapid, and the mean PaCO2 fell significantly to 5.4 kPa (40.6 mm Hg) [range 5.0-6.2 kPa (37.5-46.5 mm Hg)] within 20-60 min. No adverse effect was recognized. Inhaled frusemide should be considered for treatment of acute asthma refractory to conventional therapy.

Furosemide given by inhalation ameliorates acute exacerbation of asthma.

Previous studies have suggested that inhaled furosemide may have a protective effect against a wide variety of bronchoconstrictor agents, but a therapeutic effect has not been established in acute exacerbation of asthma. The purpose of this study was to investigate whether inhaled furosemide would exhibit any therapeutic benefit in acute asthma. We conducted a double-blind, placebo-controlled, randomized study in 40 patients with acute mild or moderate exacerbation of asthma. All patients received intravenous (i.v.) aminophylline 250 mg for 90 min and i.v. hydrocortisone 100 mg at entry. After randomization, 3 patients were excluded from the final analysis. At 30 min after starting i.v. aminophylline, 20 patients were given inhaled furosemide 20 mg and 17 patients received normal saline as placebo-control. Both inhalations were given by a jet nebulizer. The baseline forced expiratory volume at 1 sec (FEV1), peak expiratory flow rate (PEFR), and serum concentration of theophylline did not differ between the two groups. An increase in FEV1 in the furosemide group by 28.2 +/- 5.9% (mean +/- SE) was noted at 60 min, and this was significantly higher than in the control group. PEFR at 60 min was also significantly higher in the furosemide group than in control group. We conclude that inhaled furosemide has a bronchodilator effect on mild to moderate exacerbation of asthma when it is used with i.v. theophylline. Inhaled furosemide may benefit certain acute asthma patients, especially those suffering complications from the adverse effects of beta 2-agonists.

Magnetic resonance relaxation times in acute hydrostatic pulmonary edema induced by noradrenaline in rats.

Models of pulmonary edema have been used to study the nuclear magnetic resonance (NMR) characteristics of lung water. Several investigators have measured changes in the relaxation times in the permeability type of pulmonary edema, but relatively few have measured relaxation times in the hydrostatic type of pulmonary edema. In this study we determined the characteristics of NMR relaxation times T1, T2 (Hahn spin-echo decay) and water content in acute hydrostatic pulmonary edema induced by noradrenaline administration in rats. Changes in T1 and T2 showed a significant prolongation in hydrostatic pulmonary edema. T2 decay curves for peripheral lung tissues were multiexponential and fit two components [T2 fast (T2f) and T2 slow (T2s)]. With two-component T2 analysis, T2s showed greater prolongation than did T2f. The increase in T2s was significantly correlated with an increase in water content, but the increase in the T2f value was not correlated with water content or with a change in T2s. The T2s component, which likely reflected changes in interstitial water, was more closely related than the T2f component to an increase in water content in hydrostatic pulmonary edema. Results suggested that regional changes in hydrostatic pulmonary edema may be evaluated by multicomponent T2 analysis.

Effect of the NADPH oxidase inhibitor apocynin on septic lung injury in guinea pigs.

Reactive oxygen species (ROS) produced by NADPH oxidase activation in neutrophils play a major role in mediating sepsis-induced acute lung injury. To provide insight into whether the NADPH oxidase inhibitor apocynin might attenuate oxidant-induced lung injury, we examined the effect of apocynin on (1) sepsis-induced lung injury in guinea pigs, (2) ROS generation by LPS-stimulated neutrophils measured by chemiluminescence (CL), and (3) LPS-stimulated neutrophil-mediated human umbilical vein endothelial cell (HUVEC) injury assessed by 51Cr release. Sepsis-induced lung injury in guinea pigs was assessed by comparing 125I-labeled albumin concentrations in lung tissue and bronchoalveolar lavage (BAL) fluid relative to plasma (L/P and BAL/P), lung wet-to-dry weight ratios, and the number of neutrophils in BAL fluid. The lung wet-to-dry weight ratio, L/P, and the number of neutrophils in BAL fluid decreased after pretreatment and post-treatment with apocynin. BAL/P decreased upon pretreatment but not upon post-treatment with apocynin. Apocynin at concentrations from 10 to 100 micrograms/ml significantly reduced LPS-stimulated neutrophil CL and neutrophil-mediated HUVEC 51Cr release. We conclude that the NADPH oxidase inhibitor apocynin attenuates (1) sepsis-induced lung injury in guinea pigs, (2) neutrophil ROS generation measured by CL, and (3) neutrophil-mediated HUVEC injury assessed by 51Cr release.

TGF-beta 1 causes increased endothelial ICAM-1 expression and lung injury.

Neutrophil adherence to vascular endothelium is partially mediated by adhesion molecules, including intracellular adhesion molecule 1 (ICAM-1), on endothelial cells. We examined the effect of transforming growth factor-beta 1 (TGF-beta 1) on the expression of ICAM-1 in human umbilical vein endothelial cells (HUVEC). TGF-beta 1 (1 ng/ml) increased ICAM-1 and ICAM-1 mRNA expression in HUVEC, as assessed by flow cytometry and Northern blot analysis, respectively. In addition, we investigated whether exogenous recombinant TGF-beta 1 can cause neutrophil-mediated lung injury in guinea pigs. The plasma half-life of 125I-labeled TGF-beta 1 in guinea pigs was 4.6 +/- 0.1 min, and the 125I activity was 2.8 +/- 0.2% 8 h after injection. The ratio of 125I-labeled albumin concentration in lung tissue and bronchoalveolar lavage (BAL) fluid to that in plasma, lung wet-to-dry weight ratio, numbers of neutrophils in BAL fluid, and numbers of neutrophils per alveolus in fixed lung sections increased in guinea pigs that received a high dose of TGF-beta 1 (25 micrograms i.v. followed by 2 micrograms/h for 8 h) compared with the control group. These results suggest that TGF-beta 1 causes neutrophil-mediated lung injury, possibly through upregulation of ICAM-1 on endothelial cells, and might be important in the pathogenesis of lung injury.

The protein kinase C inhibitor, H-7, induces acute lung injury in guinea pigs.

OBJECTIVES: To determine if the protein kinase C inhibitor, H-7, alone can cause acute lung injury. In cell studies, H-7 inhibited phorbol myristate acetate-induced neutrophil oxygen radical release. Additionally, one animal study demonstrated that H-7 inhibited phorbol myristate acetate-induced lung injury. There have been no studies on the effect of H-7 alone on lung function or on neutrophil release of oxygen radicals. DESIGN: Prospective, randomized, laboratory study along with in vitro studies using flow cytometry and lucigenin-dependent chemiluminescence. SETTING: Experimental laboratory. SUBJECTS: Specific, pathogen-free guinea pigs and isolated human peripheral neutrophils. INTERVENTIONS: Guinea pigs were randomized into three experimental groups: saline control, H-7 low dose (2 mg/kg bolus + 0.2 mg/kg/hr), and H-7 high dose (6 mg/kg bolus + 0.5 mg/kg/hr). Human neutrophils were randomized into control and experimental groups. The effects of H-7 on pulmonary permeability in guinea pigs were examined over an 8-hr period. MEASUREMENTS AND MAIN RESULTS: We measured the wet/dry weight ratio as an index of pulmonary edema and we measured the concentration ratios of 125I-labeled albumin in lung tissue and in bronchoalveolar lavage fluid and compared the ratios with those values in plasma as indices of pulmonary permeability. We also studied the in vitro effect of H-7 on human neutrophil oxygen radical production, using flow cytometry and lucigenin-dependent chemiluminescence. By flow cytometry, we measured oxygen radical production using the 2',7'-dichlorofluorescin and hydroethidine assays. The 2',7'-dichlorofluorescin assay mainly measures hydrogen peroxide, while the hydroethidine assay measures either superoxide anion alone or in combination with other oxygen intermediaries like hydrogen peroxide. Neutrophils (5 x 10(5)) were obtained by Ficoll-Hypaque gradient centrifugation and were incubated with H-7 (5, 25, 100 microM). In the H-7 high-dose group, wet/dry weight ratio, and 125I-labeled albumin ratios in lung/plasma, and bronchoalveolar lavage/plasma were significantly increased (p < .05 for each ratio). Pulmonary endothelial gap and subendothelial bleb formation were demonstrated in the high-dose group by electron microscopy. One hundred micromols of H-7 caused a small, significant decrease (23.3%, p < .05) in neutrophil oxygen radical production assessed by 2',7'-dichlorofluorescin. H-7 had no other effects on neutrophil oxygen radical production. H-7 did not stimulate neutrophil chemiluminescence; it decreased chemiluminescence. CONCLUSIONS: a) Protein kinase C inhibition with high-dose H-7 increased wet/dry weight and albumin in lung/plasma and bronchoalveolar lavage/plasma ratios in guinea pigs; b) the H-7 high-dose group demonstrated damaged pulmonary endothelium by electron microscopy; and c) since neutrophil oxygen radical production was not increased by H-7 as assessed by flow cytometry and chemiluminescence, it appears that H-7-induced acute lung injury and endothelial damage are not mediated by increased neutrophil oxygen radical production.