bluuebunny/crossref_metadata_2025 huggingface dataset:
X-RAY PHOTOELECTRON DIFFRACTION STUDY OF A LONG-RANGE-ORDERED ACETATE LAYER ON Ni(110)
Authors: NOWICKI M. , EMUNDTS A. , WERNER J. , PIRUG G. , BONZEL H. P.
Published: May 2003

An investigation of acetic acid adsorption on Ni(110) at room temperature by LEED and X-ray photoelectron diffraction reveals a well-ordered c(2 × 2) acetate overlayer with a molecular coverage near 0.5. Large solid angle maps of angle-resolved C 1s and O 1s intensities from this layer show intense maxima due to electron forward scattering by nearby atoms, either of the same acetate or of neighboring acetate species. The data provide strong evidence for acetate in a bidentate configuration, bonded through both oxygen atoms to the surface and aligned along the [Formula: see text] surface azimuth. A real space model for the c(2 × 2) acetate layer has been derived and single scattering cluster calculations for this model layer have been carried out for C 1s and O 1s emissions. Allowing for changes in intramolecular bond length of the acetate relative to those in a Ni-acetate complex, good agreement between experimental and theoretical C 1s and O 1s distributions was obtained.
THE UNUNITED SCAPHOID: Prognostic Factors in Delayed and Nonunions of the Scaphoid
Authors: Gupta Amit , Risitano Giovanni , Crawford Robert J. , Burke Frank D.
Published: May 2003

This study attempts to classify scaphoid nonunions, identify the prognostic indicators of scaphoid nonunions and report the clinical, functional and radiographic results of scaphoid nonunions treated by Herbert screw and bone grafting. The patient population included 51 scaphoid nonunions in 50 patients treated by Herbert screw with or without bone graft. Group I was patients with delayed union; Group II was stable nonunions, Group IIIA consisted of unstable nonunions without DISI; Group IIIB included unstable nonunions with DISI deformity. Although the overall union rate was 84%, 87% stable nonunions (Groups I and II) united compared to only 60% unstable (Groups IIIA and B). This was statistically significant using the Chi-square test at p < 0.05. Thus, delayed unions and stable nonunions unite readily but unstable and displaced nonunions have significantly lower rates of union even after Herbert screw and bone grafting.
A POLYNOMIAL DESCRIPTION OF THE RIJNDAEL ADVANCED ENCRYPTION STANDARD
Authors: ROSENTHAL JOACHIM
Published: May 2003

The paper gives a polynomial description of the Rijndael Advanced Encryption Standard recently adopted by the National Institute of Standards and Technology. Special attention is given to the structure of the S-Box.
PROCESS SELECTION METHODOLOGY FOR ADVANCED MACHINING PROCESSES
Authors: JAIN NEELESH K. , JAIN VIJAY K.
Published: May 2003

Manufacture of a product in a desired shape and size with the desired characteristics and properties depends not only on the design of the product but also on the selection of an appropriate manufacturing process(es), which requires knowledge about the various alternatives available. This paper describes the process selection methodology for unconventional or advanced machining processes (AMPs), along with a preliminary selection strategy for basic type of manufacturing process. These two tasks along with parametric optimization form the core of an integrated and automated process planning system for an advanced machining environment. The process selection methodology for the AMPs is based on elimination and ranking strategy. To facilitate the process selection, AMPs have been reclassified or regrouped according to their material application capabilities, shape or manufacturing feature generating capabilities, operational capabilities, economic aspects, and environmental aspects. The described process selection methodologies for basic manufacturing process and AMPs, have been implemented in a software named as APSPOAMPS (Automated Process Selection and Parametric Optimization of AMPs). This paper also describes the proposed reclassifications of AMPs, implementation details of the developed software along with the two test examples.
CAD-GUIDED SPRAY GUN TRAJECTORY PLANNING OF FREE-FORM SURFACES IN MANUFACTURING
Authors: CHEN HEPING , XI NING , CHEN YIFAN , DAHL JEFFREY
Published: May 2003

Automatic trajectory generation for spray painting is highly desirable for today's automotive manufacturing. Generating paint gun trajectories for free-form surfaces to satisfy paint thickness requirements is still highly challenging due to the complex geometry of free-form surfaces. In this paper, a CAD-guided paint gun trajectory generation system for free-form surfaces has been developed. The system utilizes the CAD information of a free-form surface to be painted and a paint gun model to generate a paint gun trajectory to satisfy the paint thickness requirements. The paint thickness deviation from the required paint thickness is optimized by modifying the paint gun velocity. A paint thickness verication method is also provided to verify the generated trajectories. The results of simulations have shown that the trajectory generation system achieves satisfactory performance. This trajectory generation system can also be applied to generate trajectories for many other CAD-guided robot trajectory planning applications.
MANUFACTURING SYSTEMS MODELLING USING SYSTEM DYNAMICS: FORMING A DEDICATED MODELLING TOOL
Authors: OYARBIDE A. , BAINES T. S. , KAY J. M. , LADBROOK J.
Published: May 2003

Discrete event simulation is a popular aid for manufacturing system design; however in application this technique can sometimes be unnecessarily complex. This paper is concerned with applying an alternative technique to manufacturing system design which may well provide an efficient form of rough-cut analysis. This technique is System Dynamics, and the work described in this paper has set about incorporating the principles of this technique into a computer based modelling tool that is tailored to manufacturing system design.

This paper is structured to first explore the principles of System Dynamics and how they differ from Discrete Event Simulation. The opportunity for System Dynamics is then explored, and this leads to defining the capabilities that a suitable tool would need. This specification is then transformed into a computer modelling tool, which is then assessed by applying this tool to model an engine production facility.
KERNEL-BASED DATA COMPRESSION FOR ADVANCED MANUFACTURING SYSTEM
Authors: GE MING , XU YANGSHENG
Published: May 2003

Manufacturing system is becoming larger and more complicated. Global manufacturing chains have become common in the new millennium. Internet and intranet integrate the advanced manufacturing system. To perform remote monitoring and diagnosis in such chains and systems, real-time data compression has become a core factor in the efficient and effective exchange of information exchange via computer networks. This paper presents a new technique for compressing data using a kernel-based method. Overcoming the drawbacks of support vector techniques — that is, fast decompression but slow compression — the new method exhibits high speed in both phases. In addition, the new method can also be applied for pattern classification. Based on strain signal example tests derived from sheet metal stamping operations, the new method is very effective. The proposed technology has enormous potential in the application of advanced manufacturing system monitoring and control through internet or intranet.
INTELLIGENT MANUFACTURING SYSTEMS PROJECT IRMA — LINKING VIRTUAL REALITY TO SIMULATION
Authors: RUNDE CHRISTOPH , JOOSTEN HOLGER , MERSINGER MARKUS , BIERSCHENK SABINE
Published: May 2003

An international group of industrial companies and research institutions is actually creating an integrated platform for industrial process control, process design, staff training and product design. By linking simulation and virtual reality, project IRMA (A Configurable Virtual Reality system for multi-purpose industrial manufacturing applications) is to improve manufacturing performance. The core integration module is the Delfoi INTEGRATOR™, a PC based message broker used to link a virtual environment and a production/failure database scenario, to different simulations (QUEST and ARENA material flow simulation, IGRIP robot kinematics simulation) or to programmable logic controls using their OPC interface.
DISTRIBUTED MANUFACTURING SIMULATION AS AN ENABLING TECHNOLOGY FOR THE DIGITAL FACTORY
Authors: STRASSBURGER STEFFEN , SCHMIDGALL GÜNTER , HAASIS SIEGMAR
Published: May 2003

In this article the technological possibilities offered by the interoperability standard High Level Architecture (HLA) are introduced and discussed. The main focus is hereby on manufacturing applications, but the same approach is applicable to a wide range of other scenarios, e.g. in the area of supply chains, logistics, product simulation etc.

Especially for challenging objectives like the digital factory which many enterprises are currently facing, simulation applications are gaining growing importance. While simulations nowadays are often still applied for isolated problems, the consideration of the global context has a growing importance. A solution for solving this problem is offered by the distributed simulation paradigm: simulations are no longer single purpose applications. Rather, individual simulation models can be combined with each other for serving different purposes. Coupled simulations of different parts of a factory can be used to perform global optimizations. The same paradigm can be used for entire supply chains.

For applying the distributed simulation paradigm, technological as well as organizational aspects have to be considered. On the technological side, it is necessary to integrate a certain interoperability standard into the tools which need to be coupled with each other. On the organizational level, an enterprise wide process has to be established, which defines how distributed modeling and simulation shall be applied. This article discusses solutions for both issues and illustrates them using a practical application scenario.
THE APPLICATION OF MODERN SOFTWARE ENGINEERING PRACTICES TO CONTROL ENGINEERING
Authors: BERENBACH BRAIN A. , SPOOL PETER R. , BITTERLE DIETER
Published: May 2003

Over the years, control systems have become increasingly dependent on custom software. As hardware has gotten cheaper, attention has focused on improving the processes associated with developing control system software by using approaches such as the Software Engineering Institute's Capability Maturity Model (CMM),1,2 and enabling reuse and long term cost reduction with component-based software development.

This paper discusses the application of the CMM to the software process used in control engineering and the use of component based software development. We also discuss some advanced features of the Siemens SIMATIC STEP 7 Universal Development Environment that provides the tools to plan, configure, evelop, test, troubleshoot, document and support not only PLC programs, but also entire auto, ation projects. STEP 7 also enables and support process improvement and component-based software development.
Riesz basis property of Timoshenko beams with boundary feedbackcontrol
Authors: Feng De-Xing , Xu Gen-Qi , Yung Siu-Pang
Published: May 2003

A Timoshenko beam equation with boundary feedback control is
considered. By an abstract result on the Riesz basis generation
for the discrete operators in the Hilbert spaces, we show that
the closed‐loop system is a Riesz system, that is, the sequence
of generalized eigenvectors of the closed‐loop system forms a
Riesz basis in the state Hilbert space.
Ergodicity and extremality of AMS sources and channels
Authors: Kakihara Yûichirô
Published: May 2003

Asymptotically mean stationary (AMS) sources (probability measures) and channels are considered as an extension of stationary sources and channels. It is shown that each extreme
point of the set of all AMS sources is ergodic, but not vice versa, and that each extreme point in the set of all AMS channels is ergodic, but not vice versa.
On some BK spaces
Authors: de Malafosse Bruno
Published: May 2003

We characterize the spaces sα(Δ), , and and we deal with some sets generalizing the well‐known sets
w0(λ), w∞(λ), w(λ), c0(λ), c∞(λ), and c(λ).
A zero‐inflated occupancy distribution: exact results and Poissonconvergence
Authors: Kolev Nikolai , Mutafchiev Ljuben
Published: May 2003

We introduce the generalized zero‐inflated allocation scheme of
placing n labeled balls into N labeled cells. We study the asymptotic behavior of the number of empty cells when (n, N) belongs to the “right” and “left” domain of attraction. An application to the estimation of characteristics of agreement among a set of raters which independently classify subjects into one of two categories is also indicated. The case when a large number of raters acts following the zero‐inflated binomial law with small probability for positive diagnosis is treated using the zero‐inflated Poisson approximation.
Derivations on Banach algebras
Authors: Hejazian S. , Talebi S.
Published: May 2003

Let D be a derivation on a Banach algebra; by using the
operator D2, we give necessary and sufficient conditions for
the separating ideal of D to be nilpotent. We also introduce an
ideal M(D) and apply it to find out more equivalent conditions
for the continuity of D and for nilpotency of its separating
ideal.
Solutions to H‐systems by topological and iterative methods
Authors: Amster P. , Mariani M. C.
Published: May 2003

We study H‐systems with a Dirichlet boundary data g. Under some conditions, we show that if the problem admits a solution for some (H0, g0), then it can be solved for any (H, g) close enough to (H0, g0). Moreover, we construct a solution of the problem applying
a Newton iteration.
Asymptotic behavior of solutions for a semibounded nonmonotone evolution equation
Authors: Karachalios Nikos , Stavrakakis Nikos , Xanthopoulos Pavlos
Published: May 2003

We consider a nonlinear parabolic equation involving nonmonotone
diffusion. Existence and uniqueness of solutions are obtained, employing methods for semibounded evolution equations. Also shown is the existence of a global attractor for the corresponding dynamical system.
Bounded solutions of Carathéodory differential inclusions: a bound sets approach
Authors: Andres Jan , Malaguti Luisa , Taddei Valentina
Published: May 2003

A bound sets technique is developed for Floquet problems of Carathéodory differential inclusions. It relies on the construction of either continuous or locally ipschitzian Lyapunov‐like bounding functions. Proceeding sequentially, the existence of bounded trajectories is then obtained. Nontrivial examples are supplied to illustrate our approach.
Contribution of von Willebrand Factor to Thrombus Formation on Neointima of Rabbit Stenotic Iliac Artery Under High Blood-Flow Velocity
Authors: Yamashita Atsushi , Asada Yujiro , Sugimura Hiroshi , Yamamoto Hiroshi , Marutsuka Kousuke , Hatakeyama Kinta , Tamura Shozo , Ikeda Yasuo , Sumiyoshi Akinobu
Published: May 2003

Objective—

It has become clear that von Willebrand factor (vWF) plays important roles in platelet adhesion and aggregation under high blood-flow velocity conditions observed in stenotic atherosclerotic arteries. However, its roles in thrombus formation in vivo on diseased arteries have not been fully understood. We examined the contribution of vWF to thrombus formation and subsequent intimal growth by using a repeated balloon-injury model in rabbits.

Methods and Results—

Rabbit iliac arteries 4 weeks after a first balloon injury showed 37% luminal stenosis by neointimal growth, and blood velocity increased by 2.1 times compared with that of uninjured arteries. The second balloon injury induced fibrin-rich thrombus formation on the injured neointima. Intravenous administration of a monoclonal antibody against vWF (AJW200, 1.0 mg/kg body weight) remarkably prevented botrocetin-induced platelet aggregation ex vivo for 2 days; moreover, thrombus formation, cell proliferation, and subsequent neointimal growth were significantly reduced at 30 minutes, 5 days, and 4 weeks, respectively, after the second balloon injury.

Conclusions—

These results indicate that vWF plays a potent role in fibrin-rich thrombus formation on the neointima under high blood-flow velocity conditions. Inhibition of plasma vWF activity might be effective for the reduction of thrombus formation and/or subsequent neointimal development after coronary interventions.
Lysosomal Enzymes Are Released From Cultured Human Macrophages, Hydrolyze LDL In Vitro, and Are Present Extracellularly in Human Atherosclerotic Lesions
Authors: Hakala Jukka K. , Oksjoki Riina , Laine Petri , Du Hong , Grabowski Gregory A. , Kovanen Petri T. , Pentikäinen Markku O.
Published: May 2003

Objective—Human atherosclerotic lesions have been shown to contain lipid droplets and vesicles resembling those of in vitro enzymatically modified LDL. However, little is known about the hydrolytic enzymes in the arterial intima that induce fusion of LDL particles and so produce lipid droplets or that induce foam cell formation.

Methods and Results—Human coronary atherosclerotic lesions obtained at surgery and at autopsy were stained for lysosomal acid lipase and cathepsin D. The extracellular areas of macrophage-rich intimal regions of the atherosclerotic lesions stained positively for both cathepsin D and lysosomal acid lipase, whereas normal arteries were negative. When monocyte-derived macrophages were incubated with opsonized zymosan to stimulate the release of lysosomal enzymes from the cells and LDL was incubated with the macrophage-conditioned media, the apolipoprotein B-100, cholesteryl esters, and triacylglycerols of LDL were hydrolyzed. These hydrolytic modifications rendered the LDL particles unstable and induced their fusion. Cultured macrophages and smooth muscle cells took up the hydrolase-modified LDL particles avidly and were transformed into foam cells.

Conclusions—Our in vivo and in vitro results suggest that lysosomal enzymes released from macrophages may induce hydrolytic modification of LDL and foam cell formation in the human arterial intima.
Small, Dense LDL and Elevated Apolipoprotein B Are the Common Characteristics for the Three Major Lipid Phenotypes of Familial Combined Hyperlipidemia
Authors: Ayyobi Amir F. , McGladdery Sandra H. , McNeely Marguerite J. , Austin Melissa A. , Motulsky Arno G. , Brunzell John D.
Published: May 2003

Objective—

Familial combined hyperlipidemia (FCHL) is associated with variable lipid and lipoprotein phenotypes arbitrarily defined as type IIa, IIb, and IV based on plasma total cholesterol and triglyceride levels. This study sought to characterize consistent lipoprotein and lipid abnormalities across the 3 lipoprotein phenotypes in 62 patients with documented FCHL (IIa [n=14], IIb [n=19], and IV [n=29]) and 44 healthy individuals.

Methods and Results—

The lipoprotein cholesterol distribution was determined over 38 fractions obtained by density gradient ultracentrifugation. As expected, FCHL patients with hypertriglyceridemia (IIb and IV) had higher cholesterol levels in VLDL than IIa, whereas IIa showed higher cholesterol in the big, buoyant LDL and in HDL. LDL cholesterol was higher in IIb than IV; most of the increase in LDL cholesterol was associated with big, buoyant LDL rather than small, dense LDL (sdLDL). The differences in lipoproteins between phenotypes were attributable to changes in VLDL and big, buoyant LDL levels. Comparison of the FCHL patients with healthy individuals showed a significant elevation in plasma apolipoprotein B levels and sdLDL in all 3 FCHL phenotypes.

Conclusions—

Although triglyceride and cholesterol levels are variable by lipoprotein phenotype, sdLDL and elevated plasma apolipoprotein B levels are consistent characteristics of FCHL shared by the 3 different lipoprotein phenotypes.
Inhibition of Purified Factor Xa Amidolytic Activity May Not Be Predictive of Inhibition of In Vivo Thrombosis
Authors: Sinha Uma , Lin Pei Hua , Edwards Susan T. , Wong Paul W. , Zhu Bingyan , Scarborough Robert M. , Su Ting , Jia Zhaozhong J. , Song Yonghong , Zhang Penglie , Clizbe Lane , Park Gary , Reed Andrea , Hollenbach Stanley J. , Malinowski John , Arfsten Ann E.
Published: May 2003

Objective—

In this study we test the hypothesis that blood/plasma-based prothrombinase assays, rather than inhibition of purified factor Xa (fXa), are predictive of in vivo antithrombotic activity.

Methods and Results—

Six fXa inhibitors with equivalent nanomolar K
i
were studied in thrombin generation assays using human plasma/blood and endogenous macromolecular substrate. In all assays, benzamidine inhibitors were more potent (100 to 800 nmol/L) than the aminoisoquinolines (5 to 58 μmol/L) or neutral inhibitors (3 to10 μmol/L). A similar rank order of compound inhibition was also seen in purified prothrombinase assays as well as in a rabbit model of deep vein thrombosis.

Conclusions—

Assays using prothrombinase with protein substrates are better predictors of in vivo efficacy than fXa K
i
using amidolytic substrates.
Plasma PAI-1 Levels Are More Strongly Related to Liver Steatosis Than to Adipose Tissue Accumulation
Authors: Alessi Marie-Christine , Bastelica Delphine , Mavri Alenka , Morange Pierre , Berthet Bruno , Grino Michel , Juhan-Vague Irene
Published: May 2003

Objective—

Because obesity and insulin resistance (IR) are strongly associated with liver steatosis (LS), we investigated the relation between the degree of LS and plasminogen activator inhibitor-1 (PAI-1) in
ob/ob
mice, in C57/BL6 mice with alcoholic LS, and in severely obese humans.

Methods and Results—

In both mouse models, plasma PAI-1 levels were associated with PAI-1 expression in the liver and with the degree of LS. Liver PAI-1 antigen was associated with the tumor necrosis factor receptor-II (TNFRII) antigen, whereas association with TNF antigen content was found in
ob/ob
mice only. No significant correlation between plasma PAI-1 and PAI-1 expression in adipose tissue of
ob/ob
mice was observed. Furthermore, the relation between plasma PAI-1 levels and body weight was positive in
ob/ob
mice but negative in C57/BL6 mice (both
P
<0.001). In humans, PAI-1 levels were correlated with the degree of LS, and 26% of plasma PAI-1 activity was independently explained by LS and serum insulin levels.

Conclusions—

Plasma PAI-1 levels are more closely related to fat accumulation and PAI-1 expression in the liver than in adipose tissue. In steatotic liver, PAI-1 antigen content is associated with those of TNF and TNFRII. Therefore, we suggest that TNF pathway dysregulation in LS could be involved in increased plasma PAI-1 in obesity with IR.
Mechanisms of Renal Structural Alterations in Combined Hypercholesterolemia and Renal Artery Stenosis
Authors: Chade Alejandro R. , Rodriguez-Porcel Martin , Grande Joseph P. , Zhu Xiangyang , Sica Vincenzo , Napoli Claudio , Sawamura Tatsuya , Textor Stephen C. , Lerman Amir , Lerman Lilach O.
Published: May 2003

Objective—

Atherosclerotic renovascular disease (ARVD) aggravates renal scarring more than other causes of renal artery stenosis (RAS), but the underlying pathogenic mechanisms of this potential profibrotic effect remain unclear. We tested the hypothesis that coexistence of atherosclerosis and RAS interferes with renal tissue remodeling.

Methods and Results—

Single-kidney hemodynamics and function were quantified in vivo with electron-beam computed tomography in 3 groups of pigs (n=7 each): normal pigs, pigs 12 weeks after induction of unilateral RAS (RAS group), and pigs with similar-degree RAS fed a 12-week 2% hypercholesterolemic diet (HC+RAS, simulating early ARVD). Kidneys were studied ex vivo by Western blotting and immunohistochemistry. Renal volume, renal blood flow, and glomerular filtration rate were similarly decreased in RAS and HC+RAS ischemic kidneys, accompanied by similar increased expression of profibrotic factors like transforming growth factor-β, tissue inhibitor of metalloproteinase-1, and plasminogen activator inhibitor-1. Nevertheless, HC+RAS kidneys showed increased intrarenal fibrosis compared with RAS-only kidneys. Furthermore, expression of nuclear factor-κB was increased, expression of extracellular (matrix metalloproteinase-2) and intracellular (ubiquitin) protein degradation systems was decreased, and apoptosis was blunted.

Conclusions—

Diet-induced HC superimposed on RAS accelerates the development of fibrosis in the stenotic kidney by amplifying profibrotic mechanisms and disrupting tissue remodeling. These alterations might contribute to renal disease progression in ARVD and might account for the increased propensity for end-stage renal disease.
The p17 Cleaved Form of Caspase-3 Is Present Within Viable Macrophages In Vitro and in Atherosclerotic Plaque
Authors: Nhan Thomas Q. , Liles W. Conrad , Chait Alan , Fallon John T. , Schwartz Stephen M.
Published: May 2003

Objective—

In vitro studies of macrophage death in response to oxidized LDL (oxLDL) were undertaken as a model for the formation of the necrotic core of atherosclerotic plaque.

Methods and Results—

Thioglycollate-elicited mouse peritoneal macrophages avidly incorporated both oxLDL and acetylated LDL (acLDL) to become foam cells. oxLDL-treated macrophages, but not acLDL-treated macrophages, showed nearly 100% death, with characteristics consistent with apoptosis, including cell surface phosphatidylserine exposure, intracellular caspase-3 activity, cleavage of caspase-3 substrates, and DNA fragmentation, as shown by TUNEL assay. The activated form of caspase-3 (p17 cleaved form) was present in attached, viable macrophages before exposure to oxLDL. This p17 form was also found in apparently viable as well as in TUNEL-positive cells within atherosclerotic lesions of chow-fed apolipoprotein E–deficient (ApoE
−/−
) mice. The amount of p17 caspase-3 was reduced by in vitro blockade of FasL with an FasL-blocking antibody and was absent in macrophages from
lpr/lpr
mice, which lack functional Fas. Moreover,
lpr/lpr
macrophages resisted oxLDL cytotoxicity.

Conclusions—

The naturally occurring Fas-FasL induction of caspase-3 cleavage after macrophage attachment may represent an important physiologic mechanism that primes for cytotoxicity by oxLDL and possibly, other death-inducing molecules.
Probing the Contribution of
I
Ks
to Canine Ventricular Repolarization
Authors: Volders Paul G.A. , Stengl Milan , van Opstal Jurren M. , Gerlach Uwe , Spätjens Roel L.H.M.G. , Beekman Jet D.M. , Sipido Karin R. , Vos Marc A.
Published: May 2003

Background—

In large mammals and humans, the contribution of
I
Ks
to ventricular repolarization is still incompletely understood.

Methods and Results—

In vivo and cellular electrophysiological experiments were conducted to study
I
Ks
in canine ventricular repolarization. In conscious dogs, administration of the selective
I
Ks
blocker HMR 1556 (3, 10, or 30 mg/kg PO) caused substantial dose-dependent QT prolongations with broad-based T waves. In isolated ventricular myocytes under baseline conditions, however,
I
Ks
block (chromanols HMR 1556 and 293B) did not significantly prolong action potential duration (APD) at fast or slow steady-state pacing rates. This was because of the limited activation of
I
Ks
in the voltage and time domains of the AP, although at seconds-long depolarizations, the current was substantial. Isoproterenol increased and accelerated
I
Ks
activation to promote APD
95
shortening. This shortening was importantly reversed by HMR 1556 and 293B. Quantitatively similar effects were obtained in ventricular-tissue preparations. Finally, when cellular repolarization was impaired by
I
Kr
block,
I
Ks
block exaggerated repolarization instability with further prolongation of APD.

Conclusions—

Ventricular repolarization in conscious dogs is importantly dependent on
I
Ks
.
I
Ks
function becomes prominent during β-adrenergic receptor stimulation, when it promotes AP shortening by increased activation, and during
I
Kr
block, when it limits repolarization instability by time-dependent activation. Unstimulated
I
Ks
does not contribute to cellular APD at baseline. These data highlight the importance of the synergism between an intact basal
I
Ks
and the sympathetic nervous system in vivo.
Adjuvant Treatment With a Glycoprotein IIb/IIIa Receptor Inhibitor Increases the Therapeutic Window for Low-Dose Tissue Plasminogen Activator Administration in a Rat Model of Embolic Stroke
Authors: Zhang Li , Zhang Zheng Gang , Zhang Ruilan , Morris Daniel , Lu Mei , Coller Barry S. , Chopp Michael
Published: May 2003

Background—

Platelet aggregation and fibrin deposition are key events leading to microvascular thrombosis and progressive impairment of downstream microvascular perfusion after stroke. We tested the hypothesis that inhibition of platelet function with a GP IIb/IIIa receptor antagonist would increase the efficacy and safety and increase the time window for thrombolytic therapy for stroke with full- and half-dose tissue plasminogen activator (tPA).

Methods and Results—

Rats were subjected to embolic middle cerebral artery occlusion. Four hours after ischemia, rats were treated with 7E3 F(ab′)
2
(6 mg/kg) in combination with tPA at doses of 10 and 5 mg/kg, tPA alone at a dose of 10 or 5 mg/kg, 7E3 F(ab′)
2
(6 mg/kg) alone, or saline. Combination treatment with 7E3 F(ab′)
2
and tPA (full- or half-dose) significantly (
P
<0.05) reduced infarct volume and neurological deficits compared with saline-treated rats. However, treatment with 7E3 F(ab′)
2
or tPA (full- or half-dose) alone did not reduce infarct volume. Quantitative measurements of cerebral microvessels perfused by FITC-dextran revealed that combination treatment with 7E3 F(ab′)
2
and full-dose tPA significantly (
P
<0.05) increased the percentage of FITC-dextran–perfused vessels compared with saline and full-dose tPA–treated rats. In addition, treatment with 7E3 F(ab′)
2
in combination with full-dose tPA significantly (
P
<0.05) decreased microvascular platelet accumulation and matrix metalloproteinase 9 immunoreactivity and protected against loss of collagen IV immunoreactivity.

Conclusions—

Combination treatment with 7E3 F(ab′)
2
with full- and half-dose tPA at 4 hours after ischemia significantly reduces infarct volume and improves neurological outcome. Enhancement of patency and integrity of cerebral microvessels most likely contributes to the benefits observed with this combination therapy.
Role of L-Type Calcium Channels in Pacing-Induced Short-Term and Long-Term Cardiac Memory in Canine Heart
Authors: Plotnikov Alexei N. , Yu Hangang , Geller J. Christoph , Gainullin Ravil Z. , Chandra Parag , Patberg Kornelis W. , Friezema Steven , Danilo Peter , Cohen Ira S. , Feinmark Steven J. , Rosen Michael R.
Published: May 2003

Background—

We tested the hypothesis that
I
Ca,L
is important to the development of cardiac memory.

Methods and Results—

The effects of L-type Ca
2+
channel blockade and β-blockade were tested on acutely anesthetized and on chronically instrumented, conscious dogs. Short-term memory (STM) was induced by 2 hours of ventricular pacing and long-term memory (LTM) by ventricular pacing for 21 days. STM dogs received placebo, nifedipine, or propranolol, and LTM dogs received placebo, atenolol, or amlodipine. AT
1
receptor blockade (candesartan) and ACE inhibition (trandolapril) were also tested in LTM. Microelectrodes were used to record transmembrane potentials from isolated epicardial and endocardial slabs using a protocol simulating STM in intact animals. Left ventricular epicardial myocytes from LTM or sham control dogs were dissociated, and
I
Ca,L
was recorded (whole-cell patch-clamp technique). Evolution of STM and LTM was attenuated by
I
Ca,L
blockers but not β-blockers. Neither AT
1
receptor blockade nor ACE inhibition suppressed LTM. In microelectrode experiments, pacing induced an epicardial-endocardial gradient change mimicking STM that was suppressed by nifedipine. In patch-clamp experiments, peak
I
Ca,L
density in LTM and control were equivalent, but activation was more positive and time constants of inactivation longer in LTM (
P
<0.05).

Conclusions—

I
Ca,L
blockade but not β-adrenergic blockade suppresses cardiac memory. LTM evolution is unaffected by angiotensin II blockade and is associated with altered
I
Ca,L
kinetics.
Phased-Array Intracardiac Echocardiography Monitoring During Pulmonary Vein Isolation in Patients With Atrial Fibrillation
Authors: Marrouche Nassir F. , Martin David O. , Wazni Oussama , Gillinov A. Marc , Klein Allan , Bhargava Mandeep , Saad Eduardo , Bash Dianna , Yamada Hirotsugu , Jaber Wael , Schweikert Robert , Tchou Patrick , Abdul-Karim Ahmad , Saliba Walid , Natale Andrea
Published: May 2003

Background—

The objective of this study was to assess the impact of intracardiac echocardiography (ICE) on the long-term success and complications in patients undergoing pulmonary vein isolation (PVI) for treatment of atrial fibrillation (AF).

Methods and Results—

Three hundred fifteen patients underwent PVI for treatment of AF. Each patient underwent ostial isolation of all PVs using a cooled-tip ablation catheter. PVI was performed using circular mapping (CM) alone (group 1, 56 patients), CM and ICE (group 2, 107 patients), and CM and ICE with titration of radiofrequency energy based on visualization of microbubbles by ICE (group 3, 152 patients). After a mean follow-up time of 417±145 days, 19.6% (11 of 56), 16.8% (18 of 107), and 9.8% (15 of 152) of patients in groups 1, 2, and 3 experienced recurrence of AF, respectively. Moreover, whereas no group 3 patient experienced severe (>70%) PV stenosis, severe PV stenosis was documented in 3 (3.5%) of 56 patients in group 1 and in 2 (1.8%) of 107 patients in group 2 (
P
<0.05). No embolic events were detected in group 3 patients.

Conclusions—

Intracardiac echocardiography improves the outcome of cooled-tip PVI. Power adjustment guided by direct visualization of microbubble formation reduces the risk of PV stenosis and improves long-term cure.
Mulibrey Heart Disease
Authors: Lipsanen-Nyman Marita , Perheentupa Jaakko , Rapola Juhani , Sovijärvi Anssi , Kupari Markku
Published: May 2003

Background—

Mulibrey nanism is a rare inherited disease characterized by growth failure and multiorgan manifestations, including constrictive pericarditis. Its long-term course, the results of pericardiectomy, and the details of myocardial involvement have not been reported previously.

Methods and Results—

We studied 49 patients (26 men) born before 1985 and followed for up to 25 years. By 1999, 25 patients (51%) had developed congestive heart failure (CHF), 19 (39%) had undergone pericardiectomy for constrictive pericarditis, 10 (22%) had died of cardiac causes, and 5 (10%) had died of noncardiac causes. Of the 19 pericardiectomized patients, 12 derived lasting clinical benefit, whereas 1 patient suffered an early noncardiac death and 6 died later of unrelieved or recurrent CHF. At echocardiography in 34 living patients, left ventricular mass adjusted for body height and weight averaged (±SEM) 149±5 g in 21 unoperated patients, 144±8 g in 13 pericardiectomized patients, and 104±7 g in 16 healthy persons matched for age and sex (
P
=0.000). Autopsies of 11 patients showed fibrotic thickening of the pericardial leaves with myocardial hypertrophy and variable but mostly mild myocardial fibrosis. Endocardial thickening was seen in 3 patients.

Conclusions—

Constrictive pericarditis, myocardial hypertrophy, and variable myocardial fibrosis constitute the main elements of Mulibrey heart disease. At least one half of patients ultimately develop CHF. Pericardiectomy generally provides clinical benefit, but in approximately one third of patients, CHF may recur because of coexisting myocardial involvement.
Temporal Trends in Sudden Cardiac Arrest
Authors: Rea Thomas D. , Eisenberg Mickey S. , Becker Linda J. , Murray John A. , Hearne Thomas
Published: May 2003

Background—

Little is known about temporal trends in survival and prognostic characteristics of patients with out-of-hospital cardiac arrest treated by emergency medical services (EMS). We hypothesized that an evolving combination of beneficial and adverse factors may contribute to temporal patterns of survival.

Methods and Results—

We evaluated a population-based cohort of EMS-treated adult patients with cardiac arrest (n=12 591) from 1977 to 2001 in King County, Washington. Time was grouped into an initial 5-year period and 5 successive 4-year periods. We sought to determine the potential impact of temporal changes in prognostic factors typically beyond EMS control termed “fate” factors (for example, patient age) and factors implemented by EMS termed “program” factors (programs of dispatcher-assisted cardiopulmonary resuscitation and basic life support defibrillation). Several characteristics associated with survival changed over time. Observed survival did not change over time among all patients with cardiac arrest (OR=0.98 [0.95, 1.01], trend for each successive time period) and improved over time among patients with witnessed ventricular fibrillation (OR=1.05 [1.01, 1.09]). In models that included all patients with cardiac arrest and controlled for fate factors, advancing time period was associated with an increase in survival (OR=1.08 [1.05, 1.11]). Conversely, in models that controlled for program factors, advancing time period was associated with a decrease in survival (OR=0.95 [0.93, 0.98]). Results were similar among patients with witnessed ventricular fibrillation.

Conclusions—

The static temporal pattern of survival from cardiac arrest appeared to result from an evolving balance of prognostic factors. Programs implemented by EMS appeared to counter adverse temporal trends in prognostic factors typically beyond EMS control.
Microvascular Filtration Is Increased in Postural Tachycardia Syndrome
Authors: Stewart Julian M.
Published: May 2003

Background—

Postural tachycardia syndrome (POTS) is related to defective peripheral vasoconstriction of dependent extremities with redistributive hypovolemia.

Methods and Results—

To test whether enhanced microvascular filtration produces leg enlargement, we studied 12 patients 13 to 19 years of age with POTS and defective leg vasoconstriction and 13 age-matched healthy control subjects, with strain-gauge plethysmography used to measure venous pressure (P
v
), forearm and calf blood flow, vascular capacitance, and the microvascular filtration coefficient (K
f
). Measurements were made while the patient was supine and at steady state during upright tilt to 35°. Supine P
v
was not different in POTS, but upright leg P
v
tended to be increased above control. Arm and leg peripheral arterial resistance was decreased in the supine and upright positions in patients with POTS compared with control subjects (
P
=0.01, upright legs). Supine K
f
was not significantly increased in the forearm in patients with POTS but was increased in the calf (9.3±2.2 versus 5.7±2.4 [10
−3
] mL/100 mL per minute per mm Hg,
P
=0.04), correlating with calf blood flow (r
s
=0.84,
P
=0.002). K
f
was invariant with orthostasis. The hydraulic contribution to upright filtered flow at 35° tilt, the product of K
f
and P
v
, was approximately twice that of control (0.41±0.09 versus 0.19±0.04 mL/100 mL per minute,
P
=0.04).

Conclusions—

Increased microvascular filtration accounts for enhanced leg swelling in patients with POTS with increased arterial blood flow.
Improving Guideline Adherence
Authors: Ansari Maria , Shlipak Michael G. , Heidenreich Paul A. , Van Ostaeyen Denise , Pohl Elizabeth C. , Browner Warren S. , Massie Barry M.
Published: May 2003

Background—

The dissemination of clinical practice guidelines often has not been accompanied by desired improvements in guideline adherence. This study evaluated interventions for implementing a new practice guideline advocating the use of β-blockers for heart failure patients.

Methods and Results—

This was a randomized controlled trial involving heart failure patients (n=169) with an ejection fraction ≤45% and no contraindications to β-blockers. Patients’ primary providers were randomized in a stratified design to 1 of 3 interventions: (1) control: provider education; (2) provider and patient notification: computerized provider reminders and patient letters advocating β-blockers; and (3) nurse facilitator: supervised nurse to initiate and titrate β-blockers. The primary outcome, the proportion of patients who were initiated or uptitrated and maintained on β-blockers, analyzed by intention to treat, was achieved in 67% (36 of 54) of patients in the nurse facilitator group compared with 16% (10 of 64) in the provider/patient notification and 27% (14 of 51) in the control groups (
P
<0.001 for the comparisons between the nurse facilitator group and both other groups). The proportion of patients on target β-blocker doses at the study end (median follow-up, 12 months) was also highest in the nurse facilitator group (43%) compared with the control (10%) and provider/patient notification groups (2%) (
P
<0.001). There were no differences in adverse events among groups.

Conclusions—

The use of a nurse facilitator was a successful approach for implementing a β-blocker guideline in heart failure patients. The use of provider education, clinical reminders, and patient education was of limited value in this setting.
Low Paraoxonase Activity Predicts Coronary Events in the Caerphilly Prospective Study
Authors: Mackness Bharti , Durrington Paul , McElduff Patrick , Yarnell John , Azam Naheed , Watt Michael , Mackness Michael
Published: May 2003

Background—

The hypothesis that paraoxonase (PON1) has a role in preventing atherosclerosis is based on experimental, transgenic, and case-control studies but has not previously been tested prospectively.

Methods and Results—

The Caerphilly Prospective Study is a cohort study of men aged 49 to 65 years observed for coronary heart disease (CHD) events (fatal and nonfatal myocardial infarction) over a mean period of 15 years. Serum PON1 activity toward paraoxon was measured in 1353 participants. PON1 activity was 20% lower in the 163 men who had a coronary event (
P
=0.039). Men in the highest quintile of PON1 activity had a decreased risk compared with those in the lowest quintile (OR 0.57 [95% CI, 0.33 to 0.96]). The inverse relationship between quintiles of serum PON1 activity and CHD risk was graded, the median change in OR across each quintile being 0.87 (0.77 to 0.98). After adjustment for all other CHD risk factors, including HDL cholesterol, this median value became 0.90 (0.78 to 1.02). PON1 was most predictive of a new CHD event in patients at highest risk by virtue of preexisting CHD (adjusted median OR for each quintile, 0.74 [0.59 to 0.93]; n=313) or the presence of other risk factors. For the highest tertile of CHD risk (n=390) calculated by the Framingham equation, adjusted median OR for each quintile was 0.84 (0.66 to 1.05); n=390.

Conclusions—

Low serum PON1 activity toward paraoxon is an independent risk factor for coronary events in men at high risk because of preexisting disease or other CHD risk factors.
Combined Steroid Treatment for Congenital Heart Surgery Improves Oxygen Delivery and Reduces Postbypass Inflammatory Mediator Expression
Authors: Schroeder Valerie A. , Pearl Jeffery M. , Schwartz Steven M. , Shanley Thomas P. , Manning Peter B. , Nelson David P.
Published: May 2003

Background—

Steroid administration during cardiopulmonary bypass is thought to improve cardiopulmonary function by modulating bypass-related inflammation. This study was designed to compare preoperative and intraoperative methylprednisolone (MP) to intraoperative MP alone with respect to postbypass inflammation and clinical outcome.

Methods and Results—

Twenty-nine pediatric patients undergoing bypass procedures were randomly assigned to receive preoperative and intraoperative MP (30 mg/kg 4 hours before bypass and in bypass prime, n=14) or intraoperative MP only (30 mg/kg, n=15). Myocardial inflammatory mediator mRNA expression was determined in paired atrial biopsies (before and after bypass) by ribonuclease protection. Before and after bypass, serum IL-6 and IL-10 were measured by ELISA. Postoperative outcome was assessed by intubation time, CICU length of stay, fluid balance, arterio-venous O
2
difference (ΔA−V
o
2
), and inotrope requirements. Compared with intraoperative MP alone, combined preoperative and intraoperative MP was associated with reduced myocardial mRNA expression for IL-6, MCP-1, and ICAM-1 both before and after bypass (
P
<0.05). Patients who received combined steroids had lower serum IL-6 and increased IL-10 at end-bypass (
P
<0.05), although differences were negligible by 24 hours. Combined MP treatment was associated with reduced fluid requirements, lower body temperature, and lower ΔA−V
o
2
for the first 24 hours after surgery (
P
<0.05), along with trends toward improvement in other clinical outcomes.

Conclusions—

Compared with intraoperative steroid treatment, combined preoperative and intraoperative steroid administration attenuates inflammatory mediator expression more effectively and is associated with improved indexes of O
2
delivery in the first 24 hours after congenital heart surgery. These findings need to be confirmed in a larger multicenter trial.
Real-Time Magnetic Resonance Imaging-Guided Coronary Catheterization in Swine
Authors: Omary Reed A. , Green Jordin D. , Schirf Brian E. , Li Yongzhong , Finn J. Paul , Li Debiao
Published: May 2003

Background—

We tested the hypothesis that real-time magnetic resonance imaging (MRI) can guide coronary artery catheterization in swine via a percutaneous femoral artery approach.

Methods and Results—

In 12 pigs, we accessed femoral arteries percutaneously. We used 6- or 7-French coronary Judkins catheters filled with dilute 4% gadolinium (Gd) contrast agent and coaxially inserted 0.030-inch diameter active guidewires as endovascular devices. For catheter tracking, we used a 2-dimensional (2D) inversion recovery–prepared spoiled gradient echo sequence at a temporal resolution of 7 frames/s. For guidewire tracking, we used 2D steady-state free precession imaging at a temporal resolution of 9 frames/s. Coronary artery catheterization under MRI guidance was successful in 12/12 pigs. Successful coronary catheterization was verified by obtaining MR angiographic images after direct catheter-based injections of dilute Gd.

Conclusions—

Real-time MRI-guided catheterization of coronary arteries in swine is feasible via a percutaneous femoral artery approach. Selective coronary MR angiography can then be performed with dilute contrast agent injections.