bluuebunny/crossref_metadata_2025 huggingface dataset:
CXC Ligand 9 Response to Malaria during Pregnancy Is Associated with Low-Birth-Weight Deliveries
Authors: Dong Shu , Kurtis Jonathan D. , Pond-Tor Sunthorn , Kabyemela Edward , Duffy Patrick E. , Fried Michal
Published: June 2012

Placental infection withPlasmodium falciparumis associated with increased levels of proinflammatory cytokines, including tumor necrosis factor alpha (TNF-α) and gamma interferon (IFN-γ), and previous studies have associated increased levels of these cytokines with low birth weight (LBW), especially for malaria-infected primigravidae. To define the contribution of TNF-α and IFN-γ networks to placental-malaria-associated LBW, we measured chemokines induced by TNF-α and IFN-γ and related them to birth weight in a birth cohort of 782 mother-infant pairs residing in an area ofP. falciparumholoendemicity in Tanzania. Among primigravidae, levels of CCL2, CXC ligand 9 (CXCL9), and CXCL13 were significantly higher during malaria infection in both the placenta and peripheral blood. Placental CXCL9 and CXCL13 levels were also higher in placental blood from secundigravidae and multigravidae. In multivariate analyses adjusted for known predictors of birth weight, malaria-infected primigravidae with placental CXCL9 levels in the lowest tertile gave birth to babies who weighed 610 g more than babies born to mothers with high CXCL9 levels. CXCL9 expression is induced by IFN-γ, and the strong association between birth weight and placental CXCL9 is consistent with previous observations relating IFN-γ to poor pregnancy outcomes.
Novel aneurysm neck reconstruction device: initial experience in an experimental preclinical bifurcation aneurysm model
Authors: Turk Aquilla , Turner Raymond D , Tateshima Satoshi , Fiorella David , Jang Kyung-Sool , Chaudry Imran , Kelly Michael
Published: June 2012

Introduction

Treatment of wide-necked bifurcation aneurysms often poses procedural and long-term outcome challenges. The initial preclinical experience with the Pulsar Vascular Aneurysm Neck Reconstruction Device (PVANRD) in a canine bifurcation model is described.

Methods

Experimental bifurcation vein pouch aneurysms were surgically created in the carotid arteries of eight dogs. Endovascular coiling of the aneurysms with assistance of the PVANRD was performed in all cases with acute performance compared with Y-stenting.

Results

Twelve devices were deployed in the eight cases. Deployment of the devices was straightforward and successfully protected the parent artery and maintained patency of the bifurcation in all cases, despite the use of oversized coils.

Conclusion

The PVANRD is a novel bifurcation stent that facilitates treatment of wide-necked bifurcation aneurysms compared with currently available adjunctive devices.
A Curator's Tools and To-Do List
Authors: Meeker Kelly
Published: June 2012

A curator takes objects and creates a meaningful experience by organizing them within a useful context. This model is a blueprint for the future of learning, where the role of the learning professional is to enable meaningful consumption of information.This to do list is your guide to start implementing curation in your organization, with recommendations for creating, collecting and sharing-and building a culture of open conversation.
Chasing Down the Elusive Credits for Facts and Fictions in Learning and Improvement
Authors: Christensen Brett , Wallace Guy W.
Published: June 2012

"Only 20 percent of performance issues are rooted in the individual versus the system (or environment)." You may have lost count of the many times this well-known phrase has been repeated. It's popular, but is it true? And more importantly from whence did it come?
How to Build and Lead Successful Online Communities: How Is A Community Different From A Network?
Authors: Laycock Nic
Published: June 2012

In Part 2 of 4 in his series on learning communities, eLearn contributor Nic Laycock discusses what distinguishes a community from a network.
Redefining, Reinventing, and Rebuilding Schools for the 21st Century
Authors: Levin-Goldberg Jennifer
Published: June 2012

In the words of acclaimed author, Thomas Freidman, our world has gone flat. The workforce has gone global galvanizing international competition. The billion dollar question is Do our students have the skills to succeed and excel in this 21st century market? According to an exhaustive 2006 study conducted by The Conference Board, Corporate Voices for Working Families, Partnership for 21st Century Skills, and the Society for Human Resource Management, the answer is a grim no. The next question should be "How do we rectify this?" The potential solutions are to redefine, reinvent, and rebuild our schools to mirror 21st century exigencies. This article offers effective, judicious, and manifold actions educational institutions can immediately execute to engender 21st century workforce ready graduates.
The Universal Campus: An open virtual 3-D world infrastructure for research and education
Authors: Baldi Pierre , Lopes Crista
Published: June 2012

The Universal Campus is a 3-D virtual world infrastructure consisting of a campus with multiple buildings and meetings rooms together with a set of avatars. The Universal Campus is built using a server-client architecture, with an OpenSim-based server and a Second Life-based client. The entire infrastructure is open and can be fully downloaded, replicated, shared, and customized. The Universal Campus enables the deployment and exploration of virtual worlds in research and education, in particular the deployment of meetings of various sizes, such as group meetings, classes, and conferences, in a 3-D virtual world where avatars can move around, view presentations, meet serendipitously, and engage in multiway communication supported by both chat and voice.
Analysis and Design of Ultra-Wideband 3-Way Bagley Power Divider Using Tapered Lines Transformers
Authors: Al Shamaileh Khair , Qaroot Abdullah , Dib Nihad , Sheta Abdelfattah , Alkanhal Majeed A.
Published: June 2012

An ultra-wideband (UWB) modified 3-way Bagley polygon power divider (BPD) that operates over a frequency range of 2–16 GHz is presented. To achieve the UWB operation, the conventional quarter-wave transformers in the BPD are substituted by two tapered line transformers. For verification purposes, the proposed divider is simulated, fabricated, and measured. The agreement between the full-wave simulation results and the measurement ones validates the design procedure.
Multiresolution Analysis for Stochastic Finite Element Problems with Wavelet‐Based Karhunen‐Loève Expansion
Authors: Proppe Carsten
Published: June 2012

Multiresolution analysis for problems involving random parameter fields is considered. The random field is discretized by a Karhunen‐Loève expansion. The eigenfunctions involved in this representation are computed by a wavelet expansion. The wavelet expansion allows to control the spatial resolution of the problem. Fine and coarse scales are defined, and the fine scales are taken into account by projection operators. The influence of the truncation level for the wavelet expansion on the computed reliability is documented.
In VivoVisualization of Heterogeneous Intratumoral Distribution of Hypoxia-Inducible Factor-1αActivity by the Fusion of High-Resolution SPECT and Morphological Imaging Tests
Authors: Fujii Hirofumi , Yamaguchi Masayuki , Inoue Kazumasa , Mutou Yasuko , Ueda Masashi , Saji Hideo , Kizaka-Kondoh Shinae , Moriyama Noriyuki , Umeda Izumi O.
Published: June 2012

Purpose. We aimed to clearly visualize heterogeneous distribution of hypoxia-inducible factor 1α(HIF) activity in tumor tissuesin vivo.Methods. We synthesized of125I-IPOS, a125I labeled chimeric protein probe, that would visualize HIF activity. The biodistribution of125I-IPOS in FM3A tumor-bearing mice was evaluated. Then, the intratumoral localization of this probe was observed by autoradiography, and it was compared with histopathological findings. The distribution of125I-IPOS in tumors was imaged by a small animal SPECT/CT scanner. The obtainedin vivoSPECT-CT fusion images were compared withex vivoimages of excised tumors. Fusion imaging with MRI was also examined.Results.125I-IPOS well accumulated in FM3A tumors. The intratumoral distribution of125I-IPOS by autoradiography was quite heterogeneous, and it partially overlapped with that of pimonidazole. High-resolution SPECT-CT fusion images successfully demonstrated the heterogeneity of125I-IPOS distribution inside tumors. SPECT-MRI fusion images could give more detailed information about the intratumoral distribution of125I-IPOS.Conclusion. High-resolution SPECT images successfully demonstrated heterogeneous intratumoral distribution of125I-IPOS. SPECT-CT fusion images, more favorably SPECT-MRI fusion images, would be useful to understand the features of heterogeneous intratumoral expression of HIF activityin vivo.
Solar Energy Prediction for Malaysia Using Artificial Neural Networks
Authors: Khatib Tamer , Mohamed Azah , Sopian K. , Mahmoud M.
Published: June 2012

This paper presents a solar energy prediction method using artificial neural networks (ANNs). An ANN predicts a clearness index that is used to calculate global and diffuse solar irradiations. The ANN model is based on the feed forward multilayer perception model with four inputs and one output. The inputs are latitude, longitude, day number, and sunshine ratio; the output is the clearness index. Data from 28 weather stations were used in this research, and 23 stations were used to train the network, while 5 stations were used to test the network. In addition, the measured solar irradiations from the sites were used to derive an equation to calculate the diffused solar irradiation, a function of the global solar irradiation and the clearness index. The proposed equation has reduced the mean absolute percentage error (MAPE) in estimating the diffused solar irradiation compared with the conventional equation. Based on the results, the average MAPE, mean bias error and root mean square error for the predicted global solar irradiation are 5.92%, 1.46%, and 7.96%. The MAPE in estimating the diffused solar irradiation is 9.8%. A comparison with previous work was done, and the proposed approach was found to be more efficient and accurate than previous methods.
Clarithromycin Suppresses Human Respiratory Syncytial Virus Infection-InducedStreptococcus pneumoniaeAdhesion and Cytokine Production in a Pulmonary Epithelial Cell Line
Authors: Yokota Shin-ichi , Okabayashi Tamaki , Hirakawa Satoshi , Tsutsumi Hiroyuki , Himi Tetsuo , Fujii Nobuhiro
Published: June 2012

Human respiratory syncytial virus (RSV) sometimes causes acute and severe lower respiratory tract illness in infants and young children. RSV strongly upregulates proinflammatory cytokines and the platelet-activating factor (PAF) receptor, which is a receptor forStreptococcus pneumoniae, in the pulmonary epithelial cell line A549. Clarithromycin (CAM), which is an antimicrobial agent and is also known as an immunomodulator, significantly suppressed RSV-induced production of interleukin-6, interleukin-8, and regulated on activation, normal T-cell expressed and secreted (RANTES). CAM also suppressed RSV-induced PAF receptor expression and adhesion of fluorescein-labeledS. pneumoniaecells to A549 cells. The RSV-inducedS. pneumoniaeadhesion was thought to be mediated by the host cell’s PAF receptor. CAM, which exhibits antimicrobial and immunomodulatory activities, was found in this study to suppress the RSV-induced adhesion of respiratory disease-causing bacteria,S. pneumoniae, to host cells. Thus, CAM might suppress immunological disorders and prevent secondary bacterial infections during RSV infection.
Mechanisms of HIV Transcriptional Regulation and Their Contribution to Latency
Authors: Schiralli Lester Gillian M. , Henderson Andrew J.
Published: June 2012

Long-lived latent HIV-infected cells lead to the rebound of virus replication following antiretroviral treatment interruption and present a major barrier to eliminating HIV infection. These latent reservoirs, which include quiescent memory T cells and tissue-resident macrophages, represent a subset of cells with decreased or inactive proviral transcription. HIV proviral transcription is regulated at multiple levels including transcription initiation, polymerase recruitment, transcription elongation, and chromatin organization. How these biochemical processes are coordinated and their potential role in repressing HIV transcription along with establishing and maintaining latency are reviewed.
Differential Tumorigenic Potential and Matriptase Activation between PDGF B versus PDGF D in Prostate Cancer
Authors: Najy Abdo J. , Won Joshua J. , Movilla Lisa S. , Kim Hyeong-Reh C.
Published: June 2012

The platelet-derived growth factors (PDGF A, B, C, and D) and their receptors (α-PDGFR and β-PDGFR) play an indispensible role in physiologic and pathologic conditions, including tumorigenesis. The transformative β-PDGFR is overexpressed and activated during prostate cancer progression, but the identification and functional significance of its complementary ligand have not been elucidated. This study examined potential oncogenic functions of β-PDGFR ligands PDGF B and PDGF D, using nonmalignant prostate epithelial cells engineered to overexpress these ligands. In our models, PDGF D induced cell migration and invasion more effectively than PDGF B in vitro. Importantly, PDGF D supported prostate epithelial cell tumorigenesis in vivo and showed increased tumor angiogenesis compared with PDGF B. Autocrine signaling analysis of the mitogen-activated protein kinase and phosphoinositide 3-kinase pathways found PDGF D–specific activation of the c-jun-NH2-kinase (JNK) signaling cascade. Using short hairpin RNA and pharmacologic inhibitors, we showed that PDGFD-mediated phenotypic transformation is β-PDGFR and JNK dependent. Importantly, we made a novel finding of PDGF D–specific increase in the shedding and activation of the serine protease matriptase in prostate epithelial cells. Our study, for the first time to our knowledge, showed ligand-specific β-PDGFR signaling as well as PDGF D–specific regulation of matriptase activity and its spatial distribution through shedding. Taken together with our previous finding that matriptase is a proteolytic activator of PDGF D, this study provides a molecular insight into signal amplification of the proteolytic network and PDGF signaling loop during cancer progression. Mol Cancer Res; 10(8); 1087–97. ©2012 AACR.
Neuropeptide TLQP-21, a VGF Internal Fragment, Modulates Hormonal Gene Expression and Secretion in GH3 Cell Line
Authors: Petrocchi Passeri Pamela , Biondini Laura , Mongiardi Maria Patrizia , Mordini Nadia , Quaresima Stefania , Frank Claudio , Baratta Mario , Bartolomucci Alessandro , Levi Andrea , Severini Cinzia , Possenti Roberta
Published: June 2012

In the present study we demonstrated that TLQP-21, a biologically active peptide derived from the processing of the larger pro-VGF granin, plays a role in mammotrophic cell differentiation. We used an established in vitro model, the GH3 cell line, which upon treatment with epidermal growth factor develops a mammotrophic phenotype consisting of induction of prolactin expression and secretion, and inhibition of growth hormone. Here we determined for the first time that during mammotrophic differentiation, epidermal growth factor also induces Vgf gene expression and increases VGF protein precursor processing and peptide secretion. After this initial observation we set out to determine the specific role of the VGF encoded TLQP-21 peptide on this model. TLQP-21 induced a trophic effect on GH3 cells and increased prolactin expression and its own gene transcription without affecting growth hormone expression. TLQP-21 was also able to induce a significant rise of cytoplasmic calcium, as measured by Fura2AM, due to the release from a thapsigargin-sensitive store. TLQP-21-dependent rise in cytoplasmic calcium was, at least in part, dependent on the activation of phospholipase followed by phosphorylation of PKC and ERK. Taken together, the present results demonstrate that TLQP-21 contributes to differentiation of the GH3 cell line toward a mammotrophic phenotype and suggest that it may exert a neuroendocrine role in vivo on lactotroph cells in the pituitary gland.
Raloxifene Acutely Relaxes Rabbit Coronary Arteries In Vitro by an Estrogen Receptor–Dependent and Nitric Oxide–Dependent Mechanism
Authors: Figtree Gemma A. , Lu Ying-qing , Webb Carolyn M. , Collins Peter
Published: June 2012

Background
—Selective estrogen receptor modulators (SERMs) have been defined as compounds that display tissue specificity with regard to estrogenic effects. They appear to share the beneficial effects of estrogen on bone and lipids but are not associated with an increased risk of breast or uterine carcinoma. Estrogen relaxes coronary arteries and has long-term protective effects on the vascular system. The effect of SERMs on the coronary vasculature is unknown. We therefore investigated the effects of the SERM raloxifene on isolated rabbit coronary arteries.

Methods and Results
—–Rings of coronary artery from adult male and nonpregnant female New Zealand White rabbits were suspended in organ baths containing Krebs solution; isometric tension was then measured. Raloxifene induced coronary arterial relaxation in male and female coronary arteries by an endothelium-dependent and estrogen receptor–dependent mechanism involving nitric oxide. Raloxifene also had a direct calcium antagonistic effect on the coronary myocyte. Estrogen, however, induced only endothelium-independent coronary arterial relaxation. The endothelium-dependent component of relaxation induced by raloxifene 10
−6
mol/L resulted in almost 100% (79±7% versus 43±3%,
P
<0.001) more relaxation than that induced by estrogen 10
−6
mol/L.

Conclusions
—These data demonstrate that raloxifene has vascular relaxing properties. The surprising finding is that the receptor-dependent effects via the endothelium are observed in coronary arteries from both male and female animals.
Treatment of Experimental Viral Myocarditis With Interleukin-10
Authors: Nishio Ryosuke , Matsumori Akira , Shioi Tetsuo , Ishida Hiroshi , Sasayama Shigetake
Published: June 2012

Background
—The T helper cell type 2–associated cytokine interleukin (IL)-10 has a variety of immunomodulatory properties. However, the effects of the cytokine on viral myocarditis remain unclear.

Methods and Results
—We studied the effects of recombinant human IL-10 (rhIL-10) fully active on mouse cells in a murine experimental model of acute viral myocarditis caused by the encephalomyocarditis virus (EMCV). Four-week-old DBA/2 mice were inoculated with EMCV (day 0). rhIL-10 (10 μg/mouse) was administered once daily, starting on day 0, and control mice received vehicle only. Survival rates were determined on day 14. Myocardial histopathology, cytokine levels in the heart by ELISA assay, and myocardial virus concentration were examined on day 6, and the expression levels of myocardial inducible nitric oxide synthase (iNOS) mRNA were measured by competitive polymerase chain reaction. The 14-day survival in mice treated with rhIL-10 was significantly higher (80%) than in the control group (30%, n=10 in each,
P
<0.05). rhIL-10 treatment significantly attenuated myocardial lesions and suppressed tumor necrosis factor-α and IL-2 in the heart. rhIL-10 treatment had little effect on myocardial virus concentration. The expression levels of myocardial iNOS mRNA were significantly decreased in the group treated with rhIL-10 (8.6±4.7 amol/mg total RNA in treated versus 26.5±7.1 amol/mg total RNA in control mice,
P
<0.05).

Conclusions
—These findings provide new insights into the in vivo effects of IL-10 on viral infection and suggest a therapeutic effect of IL-10 on viral myocarditis.
Relation of Atrial Refractoriness to Upper and Lower Limits of Vulnerability for Atrial Fibrillation/Flutter Following Implantable Ventricular Defibrillator Shocks
Authors: Katz Amos , Sweeney Robert J. , Gill Robert M. , Reid Philip R. , Prystowsky Eric N.
Published: June 2012

Background
—Implantable ventricular cardioverter defibrillator (ICD) shocks can cause atrial fibrillation/flutter (AF). This study investigated the pathogenesis of AF after ICD shocks in a canine model.

Methods and Results
—The study was conducted in 8 dogs. In 5 dogs (group 1), truncated exponential (8 ms, 78% tilt) monophasic and biphasic shocks were delivered through a bipolar epicardial (patch) or endocardial lead. After the last S1 of atrial pacing at a cycle length of 350 ms, shocks of 0.1 to 7.6 A (0.005 to 27.7 J) were delivered, timed to the atrial effective refractory period (AERP). Ventricular defibrillation thresholds were also determined. In 3 dogs (group 2), the effect of the open versus closed chest technique on AF induction was tested in the endocardial biphasic shock configuration. AF was induced in all 8 dogs and in all waveforms and configurations. Mean AF duration was 11.5±6 s, with a mean ventricular rate of 184±37 bpm. Ventricular shocks could induce AF only if they were timed between an AERP of −60 to 40 ms, −40 to 60 ms, −40 to 60 ms, and −20 to 60 ms in the epicardial monophasic, epicardial biphasic, endocardial monophasic, and endocardial biphasic configurations, respectively. The mean±SD of the upper limit of vulnerability (ULV) for AF induction (in J) was 5.2±0.6, 3.5±0.4, 5.2±1.2, and 2.5±0.1 for the epicardial monophasic, epicardial biphasic, endocardial monophasic, and endocardial biphasic configurations, respectively (
P
<0.05). The lower limit of vulnerability (LLV) was 0.8±0.1, 0.8±0.1, 0.9±0, and 0.6±0 for the epicardial monophasic, epicardial biphasic, endocardial monophasic, and endocardial biphasic configurations, respectively (
P
=NS). The ventricular defibrillation threshold (in J) for all wave forms and configurations was higher than the ULV (
P
<0.05).

Conclusions
—(1) An atrial LLV and ULV exist for ventricular ICD shock–induced AF; (2) the shock-induced AF is related to both shock intensity and its timing to AERP; and (3) avoiding this atrial window of vulnerability may minimize the risk of post-ICD shock AF.
Impaired Pulmonary Diffusion During Exercise in Patients With Chronic Heart Failure
Authors: Smith Alan A. , Cowburn Peter J. , Parker Matthew E. , Denvir Martin , Puri Sundeep , Patel Kanti R. , Cleland John G. F.
Published: June 2012

Background
—Pulmonary diffusion is impaired at rest in patients with chronic heart failure (CHF) and has been implicated in the generation of symptoms and exercise intolerance. The aim of this study was to determine whether pulmonary diffusion is impaired during exercise in CHF, to examine its relationship to pulmonary blood flow, and to consider its functional significance in relation to metabolic gas exchange.

Methods and Results
—Carbon monoxide transfer factor (TLCO) and pulmonary blood flow (Q
C
) were measured by a rebreathe technique at rest and during steady-state cycling at 30 W in 24 CHF patients and 10 control subjects. Both patients and control subjects were able to raise TLCO and Q
C
during exercise. However, the patient group had a lower diffusion for a given blood flow (TLCO/Q
C
) both at rest (3.6±0.16 and 4.8±0.23 mL · L
−1
· mm Hg
−1
;
P
<0.001) and during exercise (2.8±0.16 and 3.4±0.13 mL · L
−1
· mm Hg
−1
for CHF patients and control subjects, respectively;
P
<0.05). TLCO/Q
C
was related to the ventilatory equivalent for carbon dioxide (VEVCO
2
) production at 30 W (TLCO/Q
c
versus VEVCO
2
,
r
=−0.58,
P
<0.01) and to peak exercise oxygen consumption measured during a progressive test (TLCO/Qc versus V
o
2peak
,
r
=0.57,
P
<0.01) in these patients.

Conclusions
—Patients with CHF are able to recruit reserves of TLCO and Q
C
during exercise. However, the TLCO/Q
C
ratio is consistently impaired in these patients and relates to both exercise hyperpnea and peak exercise oxygen consumption. Whether this impairment in alveolar gas exchange is reversible in CHF and therefore is a potential target for therapy has yet to be determined.
Endothelial Vasodilator Function Is Preserved at the Spastic/Inflammatory Coronary Lesions in Pigs
Authors: Miyata Kenji , Shimokawa Hiroaki , Yamawaki Tohru , Kunihiro Ikuko , Zhou Xuchen , Higo Taiki , Tanaka Eriko , Katsumata Naoki , Egashira Kensuke , Takeshita Akira
Published: June 2012

Background
—The question of whether or not endothelial vasodilator function in the spastic coronary artery is preserved is still controversial. We recently developed a porcine model in which long-term and local treatment with interleukin-1β (IL-1β) from the adventitial site causes coronary arteriosclerotic changes and vasospastic responses to autacoids. The aim of this study was to examine the endothelial vasodilator function in our new porcine model of the spasm both in vivo and in vitro.

Methods and Results
—A segment of the porcine coronary artery was aseptically wrapped with cotton mesh that held absorbed IL-1β–bound microbeads. Two weeks after the procedure, intracoronary administration of serotonin caused coronary vasospasm at the IL-1β–treated site (n=10). Coronary vasodilatation to bradykinin, substance P, or an increase in coronary blood flow was preserved at the spastic site. Vasodilator responses to 3-morpholinosydnonimine (an NO donor) and nitroglycerin also were comparable between the 2 sites. The vasoconstricting response to
N
G
-monomethyl-
l
-arginine and the extent of the augmentation of the serotonin-induced vasoconstriction were comparable between the 2 sites. Organ chamber experiments showed that endothelium-dependent relaxations to bradykinin, the calcium ionophore A23187, and even the vasospastic agonist serotonin were preserved at the spastic site, whereas contractions to serotonin were augmented at the spastic site regardless of the presence or absence of the endothelium (n=6). Endothelium-independent relaxations to sodium nitroprusside were also preserved at the spastic site.

Conclusions
—These results indicate that endothelial vasodilator function is preserved at the spastic site and that the spasm is caused primarily by smooth muscle hypercontraction in our porcine model.
Enoxaparin Prevents Death and Cardiac Ischemic Events in Unstable Angina/Non–Q-Wave Myocardial Infarction
Authors: Antman Elliott M. , McCabe Carolyn H. , Gurfinkel Enrique P. , Turpie Alexander G. G. , Bernink Peter J. L. M. , Salein Diana , Bayes de Luna Antonio , Fox Kim , Lablanche Jean-Marc , Radley David , Premmereur Jerome , Braunwald Eugene
Published: June 2012

Background
—Low-molecular-weight heparins are attractive alternatives to unfractionated heparin (UFH) for management of unstable angina/non–Q-wave myocardial infarction (UA/NQMI).

Methods and Results
—Patients (n=3910) with UA/NQMI were randomized to intravenous UFH for ≥3 days followed by subcutaneous placebo injections or uninterrupted antithrombin therapy with enoxaparin during both the acute phase (initial 30 mg intravenous bolus followed by injections of 1.0 mg/kg every 12 hours) and outpatient phase (injections every 12 hours of 40 mg for patients weighing <65 kg and 60 mg for those weighing ≥65 kg). The primary end point (death, myocardial infarction, or urgent revascularization) occurred by 8 days in 14.5% of patients in the UFH group and 12.4% of patients in the enoxaparin group (OR 0.83; 95% CI 0.69 to 1.00;
P
=0.048) and by 43 days in 19.7% of the UFH group and 17.3% of the enoxaparin group (OR 0.85; 95% CI 0.72 to 1.00;
P
=0.048). During the first 72 hours and also throughout the entire initial hospitalization, there was no difference in the rate of major hemorrhage in the treatment groups. During the outpatient phase, major hemorrhage occurred in 1.5% of the group treated with placebo and 2.9% of the group treated with enoxaparin (
P
=0.021).

Conclusions
—Enoxaparin is superior to UFH for reducing a composite of death and serious cardiac ischemic events during the acute management of UA/NQMI patients without causing a significant increase in the rate of major hemorrhage. No further relative decrease in events occurred with outpatient enoxaparin treatment, but there was an increase in the rate of major hemorrhage.
Myocardial Uptake of
99m
Tc-N-NOET and
201
Tl During Dobutamine Infusion
Authors: Calnon Dennis A. , Ruiz Mirta , Vanzetto Gérald , Watson Denny D. , Beller George A. , Glover David K.
Published: June 2012

Background
—The myocardial uptake of
99m
Tc-sestamibi is attenuated by dobutamine stress, resulting in underestimation of ischemia.
N
-Ethyl-
N
-ethoxy-dithiocarbamato-
N
-
99m
Tc (
99m
Tc-N-NOET) is a new
99m
Tc-labeled perfusion agent that is highly extracted by the myocardium by a mechanism different from that defined for
99m
Tc-sestamibi. We therefore hypothesized that
99m
Tc-N-NOET uptake would not be attenuated by dobutamine and that
99m
Tc-N-NOET uptake would be comparable to
201
Tl uptake during dobutamine stress.

Methods and Results
—In 28 open-chest dogs, after placement of a stenosis in the left anterior descending coronary artery that reduced flow reserve by >50%, adenosine (300 μg · kg
−1
· min
−1
; n=15) or dobutamine (2.5 to 30 μg · kg
−1
· min
−1
; n=13) was infused. During adenosine stress, the stenotic-to-normal activity ratio for
99m
Tc-N-NOET was 0.55±0.05. The stenotic-to-normal flow ratio was 0.33±0.04 at the time of
99m
Tc-N-NOET injection. During dobutamine stress, the stenotic-to-normal
99m
Tc-N-NOET activity ratio was 0.63±0.04, comparable to the
201
Tl activity ratio of 0.59±0.04. The stenotic-to-normal flow ratio was 0.47±0.04 at the time of
99m
Tc-N-NOET and
201
Tl injection. The relationship between
99m
Tc-N-NOET uptake and blood flow was comparable for adenosine and dobutamine stress, with no evidence of attenuation of
99m
Tc-N-NOET extraction by dobutamine.

Conclusions
—In the presence of coronary stenoses that reduced regional flow reserve, the myocardial uptake of
99m
Tc-N-NOET and
201
Tl are closely proportional to blood flow during both adenosine and dobutamine stress, suggesting that the adverse effect of dobutamine on
99m
Tc-sestamibi uptake is a tracer-specific phenomenon rather than a generalized effect. The clinical implication of this finding is that
99m
Tc-N-NOET might be preferable to
99m
Tc-sestamibi when used with dobutamine stress for detection of coronary stenoses.
Reference Chart Derived From Post–Stent-Implantation Intravascular Ultrasound Predictors of 6-Month Expected Restenosis on Quantitative Coronary Angiography
Authors: de Feyter P. J. , Kay P. , Disco C. , Serruys P. W.
Published: June 2012

Background
—Intravascular ultrasound (IVUS)–guided stent implantation and the availability of a reference chart to predict the expected in-stent restenosis rate based on operator-dependent IVUS parameters may interactively facilitate optimal stent placement. The use of IVUS guidance protects against undue risks of dissection or rupture.

Methods and Results
—IVUS-determined post–stent-implantation predictors of 6-month in-stent restenosis on quantitative coronary angiography (QCA) were identified by logistic regression analysis. These predictors were used to construct a reference chart that predicts the expected 6-month QCA restenosis rate. IVUS and QCA data were obtained from 3 registries (MUSIC [Multicenter Ultrasound Stenting in Coronaries study], WEST-II [West European Stent Trial II], and ESSEX [European Scimed Stent EXperience]) and 2 randomized in-stent restenosis trials (ERASER [Evaluation of ReoPro And Stenting to Eliminate Restenosis] and TRAPIST [TRApidil vs placebo to Prevent In-STent intimal hyperplasia]). In-stent restenosis was defined as luminal diameter stenosis >50% by QCA. IVUS predictors were minimum and mean in-stent area, stent length, and in-stent diameter. Multiple models were constructed with multivariate logistic regression analysis. The model containing minimum in-stent area and stent length best fit the Hosmer-Lemeshow goodness-of-fit test. This model was used to construct a reference chart to calculate the expected 6-month restenosis rate.

Conclusions
—The expected 6-month in-stent restenosis rate after stent implantation for short lesions in relatively large vessels can be predicted by use of in-stent minimal area (which is inversely related to restenosis) and stent length (which is directly related to restenosis), both of which can be read from a simple reference chart.
Antiarrhythmic Efficacy of Selective Blockade of the Cardiac Slowly Activating Delayed Rectifier Current,
I

Ks

, in Canine Models of Malignant Ischemic Ventricular Arrhythmia
Authors: Lynch Joseph J. , Houle Melanie S. , Stump Gary L. , Wallace Audrey A. , Gilberto David B. , Jahansouz Hossain , Smith Garry R. , Tebben Andrew J. , Liverton Nigel J. , Selnick Harold G. , Claremon David A. , Billman George E.
Published: June 2012

Background
—To date, the lack of potent and selective inhibitors has hampered the physiological assessment of modulation of the cardiac slowly activating delayed rectifier current,
I
Ks
. The present study, using the
I
Ks
blocker L-768,673, represents the first in vivo assessment of the cardiac electrophysiological and antiarrhythmic effects of selective
I
Ks
blockade.

Methods and Results
—In an anesthetized canine model of recent (8.5±0.4 days) anterior myocardial infarction, 0.003 to 0.03 mg/kg L-768,673 IV significantly suppressed electrically induced ventricular tachyarrhythmias and reduced the incidence of lethal arrhythmias precipitated by acute, thrombotically induced posterolateral myocardial ischemia. Antiarrhythmic protection afforded by L-768,673 was accompanied by modest 7% to 10% increases in noninfarct zone ventricular effective refractory period, 3% to 5% increases in infarct zone ventricular effective refractory period, and 4% to 6% increases in QTc interval. In a conscious canine model of healed (3 to 4 weeks) anterior myocardial infarction, ventricular fibrillation was provoked by transient occlusion of the left circumflex coronary artery during submaximal exercise. Pretreatment with 0.03 mg/kg L-768,673 IV elicited a modest 7% increase in QTc, prevented ventricular fibrillation in 5 of 6 animals, and suppressed arrhythmias in 2 additional animals.

Conclusions
—The present findings suggest that selective blockade of
I
Ks
may be a potentially useful intervention for the prevention of malignant ischemic ventricular arrhythmias.
Chromosomal Mapping of Quantitative Trait Loci That Influence Renal Hemodynamic Functions
Authors: Iwai Naoharu , Kinoshita Masahiko , Shimoike Hitoshi
Published: June 2012

Background
—Impaired renal hemodynamic function has been suspected to be responsible for hypertension in the spontaneously hypertensive rat (SHR).

Methods and Results
—We measured renal hemodynamic functions, including the glomerular filtration rate, renal plasma flow, and renal vascular resistance, in an F2 rat population derived from spontaneously hypertensive and Wistar-Kyoto (WKY) rats and performed a genome-wide screening to map quantitative trait loci that influence these functions to gain insight into the relationship between renal hemodynamic functions and blood pressure control. The
D1 Mit7
locus was identified as a major locus that influenced renal hemodynamic functions, and we transferred the SHR chromosomal segment around the
D1 Mit7
locus into the WKY strain. The congenic rats exhibited impaired renal hemodynamic functions. The systolic blood pressure of the congenic rats was significantly higher than that of age-matched WKY rats, but only at nighttime. No significant differences in systolic blood pressure during daytime or diastolic blood pressure were observed between the 2 strains

Conclusions
—We have identified a chromosome segment that influences renal hemodynamic function. The SHR chromosome segment around the
D1 Mit7
locus had significant, but not dramatic, effects in increasing blood pressure in the WKY genetic background. However, further studies will be necessary to determine the significance of this locus in SHR hypertension.
Are Electrophysiological Changes Induced by Longer Lasting Atrial Fibrillation Reversible?
Authors: Rodriguez Luz-Maria , Timmermans Carl , Wellens Hein J. J.
Published: June 2012

Background
—Studies in animal hearts have shown shortening of the atrial effective refractory period (AERP) and loss of the relation between the AERP and heart rate after prolonged periods of atrial fibrillation (AF). The purposes of this study were (1) to evaluate atrial electrophysiology after a long period of sinus rhythm in patients who had longer lasting recurrent AF that was successfully treated with the Metrix Atrioverter and (2) to analyze the effect of prompt cardioversion on subsequent AF episodes and the duration of sinus rhythm.

Methods and Results
—Four patients with recurrent AF (duration, 3 to 21 years; mean±SD, 13±7.6 years) were studied after the implantation of an Atrioverter. The Atrioverter stores and analyzes 3 minutes of cardiac rhythm every hour. Before implantation, AERP was measured. During a mean follow-up of 14 months, 52 spontaneous (39 treated and 18 nontreated) AF episodes occurred while the patients were on antiarrhythmic drugs. All patients were electrophysiologically studied after they had been in sinus rhythm for at least 1000 hours (range, 1052 to 2675 hours). Before Atrioverter implantation, AF was induced by 1 atrial premature beat in 3 patients and not induced in the remaining patient. After a long period in sinus rhythm (>1000 hours), AF could be induced in the same 3 patients in the same way as before implantation. In the patient in whom no AF was induced, right AERP values measured using the single extrastimulus technique at 3 pacing cycle lengths (600, 500, and 430 ms) were similar to those before implantation.

Conclusions
—AF was still inducible by a single atrial premature beat after long episodes of sinus rhythm in 3 of 4 patients with previously longer lasting AF. In the patient in whom no AF was induced, AERP behaved like it did before implantation. In these patients with longer lasting recurrent AF, no return to “normal” atrial electrophysiology could be demonstrated.
Infection With
Helicobacter pylori
Is Not a Major Independent Risk Factor for Stable Coronary Heart Disease
Authors: Koenig Wolfgang , Rothenbacher Dietrich , Hoffmeister Albrecht , Miller Markus , Bode Guenther , Adler Guido , Hombach Vinzenz , März Winfried , Pepys Mark B. , Brenner Hermann
Published: June 2012

Background
—There is controversy about the association between
Helicobacter pylori
infection and manifestations of coronary heart disease (CHD), the potential role of the more virulent
H pylori
strains, and whether or not a positive serostatus is related to increased levels of markers of systemic inflammation.

Methods and Results
—We assessed the prevalence of an infection with
H pylori
and in particular the anti–cytotoxin-associated protein A (CagA) antibody response of the more virulent strains expressing CagA in 312 patients with stable CHD and in 479 control subjects. Serological prevalence of
H pylori
infection (IgG titer) was significantly higher in patients than in control subjects after adjustment for age and sex (44.2% versus 31.3%,
P
<0.001). After adjustment for various covariates in multiple logistic regression, the odds ratio (OR) for CHD was 1.3 (95% CI, 0.9 to 1.9) given a positive IgG serostatus. The prevalence of CagA-positive strains was 27.9% in patients and 21.7% in control subjects (
P
=0.076 adjusted for age and sex). The OR for CHD in the fully adjusted model was 1.1 (95% CI, 0.7 to 1.7). None of the inflammatory markers (C-reactive protein, fibrinogen, plasma viscosity, or leukocytes) was significantly different according to serostatus.

Conclusions
—In this large case-control study, the association of
H pylori
infection with stable CHD was strongly reduced and was no longer statistically significant after controlling for potential confounders. We also found no independent association between the more virulent strains and CHD. In addition, a positive serostatus was not associated with a systemic inflammatory response. Thus, these data do not support the hypothesis that infection with
H pylori
might be a major risk factor for stable CHD.
Methylenetetrahydrofolate Reductase Genotypes and Early-Onset Coronary Artery Disease
Authors: Mager Aviv , Lalezari Shadan , Shohat Tamar , Birnbaum Yochai , Adler Yehuda , Magal Nurit , Shohat Mordechai
Published: June 2012

Background
—Homozygosity for the common (677C→T) mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is associated with hyperhomocysteinemia, but there is uncertainty as to the association between this mutation and coronary artery disease (CAD). This study examined the association between MTHFR genotypes and age at onset of CAD.

Methods and Results
—Patients (n=169) with documented myocardial infarction or angiographically documented CAD who were aged ≤55 years at onset of CAD symptoms and DNA samples from control subjects (n=313) were studied. The prevalence of homozygosity among patients with early CAD onset (aged ≤45 years) was 28%, which was significantly higher than that in patients with later onset (13%) and in control subjects (14%) (odds ratio 2.4, 95% CI 1.24 to 4.69,
P
=0.006, and odds ratio 2.7, 95% CI 1.15 to 6.42,
P
=0.01, respectively). Plasma folate was lower in TT homozygotes who had early CAD onset than in those with later onset (
P
=0.005). Among patients with plasma folate in the lowest quintile (≤12.6 nmol/L), 31% were homozygotes, as were 45% of those with low plasma folate and early CAD onset. There was no difference in the prevalence of traditional risk factors among genotypes. The frequency of homozygosity in patients with ≤1 risk factor was higher than in those with ≥2 risk factors (30% versus 12%,
P
<0.05). In multiple regression analysis, TT homozygosity and plasma folate were independently associated with CAD, but the impact of folate was small.

Conclusions
—Homozygosity for the 677C→T mutation of MTHFR is common and is associated with an increased risk of premature CAD in this population.
Role of Bradykinin in the Vasodilator Effects of Losartan and Enalapril in Patients With Heart Failure
Authors: Davie Andrew P. , Dargie Henry J. , McMurray John J. V.
Published: June 2012

Background
—ACE inhibitors have been shown to potentiate the effects of exogenous bradykinin by inhibition of its breakdown. Despite this, there is little evidence that inhibition of endogenous bradykinin breakdown actually contributes to the effects of ACE inhibitors, or indeed, other inhibitors of the renin-angiotensin system, such as angiotensin II type I receptor (AT
1
) antagonists, and no evidence at all that it does so in patients with heart failure.

Methods and Results
—Twelve patients with heart failure (11 male, 1 female, ages 59 to 81 years) were randomized to double-blind crossover treatment with enalapril 10 mg BID followed by losartan 25 mg BID, or the reverse, each for 5 weeks. At the end of each treatment period, forearm blood flow was measured by venous occlusion plethysmography during an intrabrachial infusion of bradykinin before and after an intrabrachial infusion of Hoe-140 (a potent, selective, and long-acting bradykinin antagonist). Bradykinin caused profound vasodilatation after enalapril (peak, 357±67%) and less after losartan (peak, 230±46%). Despite this, Hoe-140 had no discernible effects after enalapril or losartan. Similarly, this was despite the finding that Hoe-140 significantly reduced vasodilatation to bradykinin after enalapril (peak, 192±35%) and losartan (peak, 66±13%).

Conclusions
—Inhibition of endogenous bradykinin breakdown does not appear to contribute to the effects of ACE inhibition or AT
1
antagonism in the forearm of patients with heart failure at rest, despite the very obvious effects of ACE inhibition compared with AT
1
antagonism on exogenous bradykinin.
Endothelial Dysfunction in Chronic Myocardial Infarction Despite Increased Vascular Endothelial Nitric Oxide Synthase and Soluble Guanylate Cyclase Expression
Authors: Bauersachs Johann , Bouloumié Anne , Fraccarollo Daniela , Hu Kai , Busse Rudi , Ertl Georg
Published: June 2012

Background
—Endothelial dysfunction of the peripheral vasculature is a well-known phenomenon in congestive heart failure that contributes to the elevated peripheral resistance; however, the underlying mechanisms have not yet been clarified.

Methods and Results
—Dilator responses, the expression of protein and mRNA of the endothelial nitric oxide synthase (eNOS), inducible NOS (iNOS), and soluble guanylate cyclase (sGC), and superoxide anion (O
2
−
) and peroxynitrite production were determined in aortic rings from Wistar rats 8 weeks after myocardial infarction and compared with those in sham-operated animals. In rats with heart failure, the concentration-response curve of the endothelium-dependent vasodilator acetylcholine (after preconstriction with phenylephrine) was significantly shifted to the right, and the maximum relaxation was attenuated. Determination of expression levels of the 2 key enzymes for NO-mediated dilations, eNOS and sGC, revealed a marked upregulation of both enzymes in aortas from rats with heart failure, whereas iNOS expression was not changed. Pretreatment with exogenous superoxide dismutase partially restored the acetylcholine-induced relaxation in aortas from rats with heart failure. Aortic basal and NADH-stimulated O
2
−
production assessed by use of lucigenin-enhanced chemiluminescence was significantly elevated in rats with chronic myocardial infarction. Peroxynitrite-mediated nitration of protein tyrosine residues was not different between the 2 groups of rats.

Conclusions
—These results demonstrate that endothelial dysfunction in ischemic heart failure occurs despite an enhanced vascular eNOS and sGC expression and can be attributed to an increase in vascular O
2
−
production by an NADH-dependent oxidase. By inactivation of NO, O
2
−
production appears to be an essential mechanism for the endothelial dysfunction observed in heart failure.
Is Pulse Pressure Useful in Predicting Risk for Coronary Heart Disease?
Authors: Franklin Stanley S. , Khan Shehzad A. , Wong Nathan D. , Larson Martin G. , Levy Daniel
Published: June 2012

Background
—Current definitions of hypertension are based on levels of systolic blood pressure (SBP) and diastolic blood pressure (DBP), but not on pulse pressure (PP). We examined whether PP adds useful information for predicting coronary heart disease (CHD) in the population-based Framingham Heart Study.

Methods and Results
—We studied 1924 men and women between 50 and 79 years of age at baseline with no clinical evidence of CHD and not taking antihypertensive drug therapy. Cox regression, adjusted for age, sex, and other risk factors, was used to assess the relations between blood pressure components and CHD risk over a 20-year follow-up. The association with CHD risk was positive for SBP, DBP, and PP, considering each pressure individually; of the 3, PP yielded the largest χ
2
statistic. When SBP and DBP were jointly entered into the multivariable model, the association with CHD risk was positive for SBP (HR, 1.22; 95% CI, 1.15 to 1.30) and negative for DBP (HR, 0.86; 95% CI, 0.75 to 0.98). Four subgroups were defined according to SBP levels (<120, 120 to 139, 140 to 159, and ≥160 mm Hg). Within each subgroup, the association with CHD risk was negative for DBP and positive for PP. A cross-classification of SBP-DBP levels confirmed these results.

Conclusions
—In the middle-aged and elderly, CHD risk increased with lower DBP at any level of SBP≥120 mm Hg, suggesting that higher PP was an important component of risk. Neither SBP nor DBP was superior to PP in predicting CHD risk.