bluuebunny/crossref_metadata_2025 huggingface dataset:
The potential of split-gate transistors as one-dimensional electron waveguides revealed through the testing and analysis of yield and reproducibility
Authors: Yang Q.-Z. , Kelly M. J. , Farrer I. , Beere H. E. , Jones G. A. C.
Published: January 2009

We study the yield and reproducibility of quantized conductance in short one-dimensional quantum wires in split-gate transistors. In order to get an unambiguous assessment, more than 500 split gates have been fabricated and tested at 1.4 K. The study clearly shows that the devices are too sensitive to the inherent dopant structures and to variations of processing. The limitations of split gates also have been revealed through the fluctuations of the pinch-off voltage and the characteristics of the first quantized plateau.
Na,K-ATPase signal transduction triggers CREB activation and dendritic growth
Authors: Desfrere Luc , Karlsson Marie , Hiyoshi Hiromi , Malmersjö Seth , Nanou Evanthia , Estrada Manuel , Miyakawa Ayako , Lagercrantz Hugo , El Manira Abdeljabbar , Lal Mark , Uhlén Per
Published: January 2009

Dendritic growth is pivotal in the neurogenesis of cortical neurons. The sodium pump, or Na,K-ATPase, is an evolutionarily conserved protein that, in addition to its central role in establishing the electrochemical gradient, has recently been reported to function as a receptor and signaling mediator. Although a large body of evidence points toward a dual function for the Na,K-ATPase, few biological implications of this signaling pathway have been described. Here we report that Na,K-ATPase signal transduction triggers dendritic growth as well as a transcriptional program dependent on cAMP response element binding protein (CREB) and cAMP response element (CRE)-mediated gene expression, primarily regulated via Ca
2+
/calmodulin-dependent protein (CaM) kinases. The signaling cascade mediating dendritic arbor growth also involves intracellular Ca
2+
oscillations and sustained phosphorylation of mitogen-activated protein (MAP) kinases. Thus, our results suggest a novel role for the Na,K-ATPase as a modulator of dendritic growth in developing neurons.
Evidence that DmMANF is an invertebrate neurotrophic factor supporting dopaminergic neurons
Authors: Palgi Mari , Lindström Riitta , Peränen Johan , Piepponen T. Petteri , Saarma Mart , Heino Tapio I.
Published: January 2009

In vertebrates the development and function of the nervous system is regulated by neurotrophic factors (NTFs). Despite extensive searches no neurotrophic factors have been found in invertebrates. However, cell ablation studies in
Drosophila
suggest trophic interaction between neurons and glia. Here we report the invertebrate neurotrophic factor in
Drosophila
, DmMANF, homologous to mammalian MANF and CDNF. DmMANF is expressed in glia and essential for maintenance of dopamine positive neurites and dopamine levels. The abolishment of both maternal and zygotic DmMANF leads to the degeneration of axonal bundles in the embryonic central nervous system and subsequent nonapoptotic cell death. The rescue experiments confirm
DmMANF
as a functional ortholog of the human
MANF
gene thus opening the window for comparative studies of this protein family with potential for the treatment of Parkinson's disease.
Cellulosic ethanol production from AFEX-treated corn stover using
Saccharomyces cerevisiae
424A(LNH-ST)
Authors: Lau Ming W. , Dale Bruce E.
Published: January 2009

Current technology using corn stover (CS) as feedstock, Ammonia Fiber Expansion (AFEX) as the pretreatment technology, and
Saccharomyces cerevisiae
424A(LNH-ST) as the ethanologenic strain in Separate Hydrolysis and Fermentation was able to achieve 191.5 g EtOH/kg untreated CS, at an ethanol concentration of 40.0 g/L (5.1 vol/vol%) without washing of pretreated biomass, detoxification, or nutrient supplementation. Enzymatic hydrolysis at high solids loading was identified as the primary bottleneck affecting overall ethanol yield and titer. Degradation compounds in AFEX-pretreated biomass were shown to increase metabolic yield and specific ethanol production while decreasing the cell biomass generation. Nutrients inherently present in CS and those resulting from biomass processing are sufficient to support microbial growth during fermentation. This platform offers the potential to improve the economics of cellulosic ethanol production by reducing the costs associated with raw materials, process water, and capital equipment.
The Paf1 complex is required for efficient transcription elongation by RNA polymerase I
Authors: Zhang Yinfeng , Sikes Martha L. , Beyer Ann L. , Schneider David A.
Published: January 2009

Regulation of RNA polymerase I (Pol I) transcription is critical for controlling ribosome synthesis. Most previous investigations into Pol I transcription regulation have focused on transcription initiation. To date, the factors involved in the control of Pol I transcription elongation are poorly understood. The Paf1 complex (Paf1C) is a well-defined factor that influences polymerase II (Pol II) transcription elongation. We found that Paf1C associates with rDNA. Deletion of genes for Paf1C subunits (
CDC73
,
CTR9
, or
PAF1
) reduces the rRNA synthesis rate; however, there is no significant alteration of rDNA copy number or Pol I occupancy of the rDNA. Furthermore, EM analysis revealed a substantial increase in the frequency of large gaps between transcribing polymerases in
ctr9
Δ mutant cells compared with WT. Together, these data indicate that Paf1C promotes Pol I transcription through the rDNA by increasing the net rate of elongation. Thus, the multifunctional, conserved transcription factor Paf1C plays an important role in transcription elongation by Pol I in vivo.
Limitations of 64-detector-row computed tomography coronary angiography: Calcium and motion but not short experience
Authors: Mir-Akbari H. , Ripsweden J. , Jensen J. , Pichler P. , Sylvén C. , Cederlund K. , Rück A.
Published: January 2009

Background: Recently, 64-detector-row computed tomography coronary angiography (CTA) has been introduced for the noninvasive diagnosis of coronary artery disease.

Purpose: To evaluate the diagnostic capacity and limitations of a newly established CTA service.

Material and Methods: In 101 outpatients with suspected coronary artery disease, 64-detector-row CTA (VCT Lightspeed 64; GE Healthcare, Milwaukee, Wisc., USA) was performed before invasive coronary angiography (ICA). The presence of >50% diameter coronary stenosis on CTA was rated by two radiologists recently trained in CTA, and separately by an experienced colleague. Diagnostic performance of CTA was calculated on segment, vessel, and patient levels, using ICA as a reference. Segments with a proximal reference diameter <2 mm or with stents were not analyzed.

Results: In 51 of 101 patients and 121 of 1280 segments, ICA detected coronary stenosis. In 274 of 1280 (21%) segments, CTA had non-diagnostic image quality, the main reasons being severe calcifications (49%), motion artifacts associated with high or irregular heart rate (45%), and low contrast opacification (14%). Significantly more women (43%) had non-diagnostic scans compared to men (20%). A heart rate above 60 beats per minute was associated with significantly more non-diagnostic patients (38% vs. 18%). In the 1006 diagnostic segments, CTA had a sensitivity of 78%, specificity of 95%, positive predictive value (PPV) of 54%, and negative predictive value (NPV) of 98% for detecting significant coronary stenosis. In 29 patients, CTA was non-diagnostic. In the remaining 72 patients, sensitivity was 100%, specificity 65%, PPV 79%, and NPV 100%. The use of a more experienced CTA reader did not improve diagnostic performance.

Conclusion: CTA had a very high negative predictive value, but the number of non-diagnostic scans was high, especially in women. The main limitations were motion artifacts and vessel calcifications, while short experience in CTA did not influence the interpretation.
From fragility to stability: a survival strategy for the Saudi monarchy
Authors: Yamani May
Published: January 2009

This paper gives a detailed, insider’s look into the history and intricacies of the royal politics of the Āl Saūd examining the factors that characterize and define the course of modern Saudi Arabia from tribal affiliations to Wahhābī muṭāw ah and muftis. The author examines the internal power struggles amidst the famous ‘Sudeiri Seven’ and their rival claimants to the throne as well as repercussions of the system and its underpinnings on the population as a whole. Oil, powerpolitics, alliances with the United States and the particular means and apparatuses of control emanating from the Najd all factor in a regime that has marginalized significant sectors of society from inhabitants of the Ḥijāz to the Shīah of the Eastern Province and which may or may not survive the effects of a population boom and high unemployment that coincide with an ever-increasing number of claimants to a rule predicated on the ‘custodianship’ of Islam’s two holiest cities.
A topography of Sunni Islamic organizations and movements in Lebanon
Authors: Imad Abdul Ghany
Published: January 2009

In this data-filled account, the author provides a concise and informative topography of Lebanon’s oft-neglected Sunni Islamic movements – dealing with their origins, orientations, founding members and various socio-political and institutional initiatives. Rare details are provided on movements and affiliated institutions – including schools, mosques and media organizations – of the Lebanese tableau where scholarly interest has been dominated by concentration on Ḥizb Allāh. Included are reviews of al-Jamā ah al-Islāmīyah (the Islamic Group); Jabhat al- Amal al-Islāmī (the Islamic Action Front); H: arakat al-Tawḥīd al-Islāmī (the Islamic Tawḥīd Movement); Ḥizb al-Taḥrīr al-Islāmī (the Islamic Liberation Party); Jamā at al-Da wah wa al-Tablı¯gh (the Da wah and Tablīgh Group); Jam iyat al-Mashārī al-Khayrīah al-Islāmı¯yah–al-Ah: bāsh (The Association of Islamic Charitable Initiatives); as well as the major Lebanese salafist movements.
An assessment of conditions in the Kurdish region of Iraq
Authors: Majid Kamal
Published: January 2009

Kamal Majid provides an insider’s assessment of the history, political dynamics, major players and current social and economic conditions in the Kurdish region of Iraq. The author outlines a state of exception that has had an ambiguous and sometimes turbulent relationship both with the previous Ba'th regime and the present Baghdad government which ultimately replaced it. The powerful rival groups of Jalāl Ṭalabānī and the Patriotic Union of Kurdistan (PUK) and Mas'ūd Barazānī and the Kurdistan Democratic Party (KDP) vie for power, control of oil resources and pipelines as well as lucrative trans-national smuggling routes at a time when services have deteriorated and material components of infrastructure have been sold off to Iran. The picture of a region run by the Peshmerga militias of the ruling parties and plagued by corruption and influence peddling in a world of shifting alliances between Turkey, occupation forces and Iran is a dim one.
𝐿log𝐿 results for the maximal operator in variable 𝐿^{𝑝} spaces
Authors: Cruz-Uribe D. , Fiorenza A.
Published: January 2009

We generalize the classical

L
log
⁡
L

L\log L

inequalities of Wiener and Stein for the Hardy-Littlewood maximal operator to variable

L
p

L^p

spaces where the exponent function

p
(
⋅
)

p(\cdot )

approaches

1
1

in value. We prove a modular inequality with no assumptions on the exponent function, and a strong norm inequality if we assume the exponent function is log-Hölder continuous. As an application of our approach we give another proof of a related endpoint result due to Hästö.
Depths of multiplier ideals and integral closure
Authors: Lee Seunghun
Published: January 2009

In this note, we study how the depths of multiplier ideals behave under restriction. We also study possible values of the depths of multiplier ideals in the filtrations induced from maximal ideal sheaves. We then use it to give a sufficient condition for the integral closedness of the product of a multiplier ideal and a power of maximal ideal sheaf in the spirit of Huneke.
Congruence for rational points over finite fields and coniveau over local fields
Authors: Esnault Hélène , Xu Chenyang
Published: January 2009

If the

ℓ
\ell

-adic cohomology of a projective smooth variety, defined over a local field

K
K

with finite residue field

k
k

, is supported in codimension

≥
1

\ge 1

, then every model over the ring of integers of

K
K

has a

k
k

-rational point. For

K
K

a

p
p

-adic field, this is proved in (Esnault, 2007, Theorem 1.1). If the model

X

\mathcal {X}

is regular, one has a congruence

|

X

(
k
)

|

≡
1

|\mathcal {X}(k)|\equiv 1

modulo

|

k

|

|k|

for the number of

k
k

-rational points (Esnault, 2006, Theorem 1.1). The congruence is violated if one drops the regularity assumption.
Rough path analysis via fractional calculus
Authors: Hu Yaozhong , Nualart David
Published: January 2009

Using fractional calculus we define integrals of the form

∫

a

b

f
(

x

t

)
d

y

t

\int _{a}^{b}f(x_{t})dy_{t}

, where

x
x

and

y
y

are vector-valued Hölder continuous functions of order

β
∈
(

1
3

,

1
2

)

\beta \in (\frac {1}{3}, \frac {1}{2})

and

f
f

is a continuously differentiable function such that

f

′

f^{\prime }

is

λ
\lambda

-Hölder continuous for some

λ
>

1
β

−
2

\lambda >\frac {1}{\beta }-2

. Under some further smooth conditions on

f
f

the integral is a continuous functional of

x
x

,

y
y

, and the tensor product

x
⊗
y

x\otimes y

with respect to the Hölder norms. We derive some estimates for these integrals and we solve differential equations driven by the function

y
y

. We discuss some applications to stochastic integrals and stochastic differential equations.
Universal inequalities for the eigenvalues of Laplace and Schrödinger operators on submanifolds
Authors: El Soufi Ahmad , Harrell Evans , Ilias Saïd
Published: January 2009

We establish inequalities for the eigenvalues of Schrödinger operators on compact submanifolds (possibly with nonempty boundary) of Euclidean spaces, of spheres, and of real, complex and quaternionic projective spaces, which are related to inequalities for the Laplacian on Euclidean domains due to Payne, Pólya, and Weinberger and to Yang, but which depend in an explicit way on the mean curvature. In later sections, we prove similar results for Schrödinger operators on homogeneous Riemannian spaces and, more generally, on any Riemannian manifold that admits an eigenmap into a sphere, as well as for the Kohn Laplacian on subdomains of the Heisenberg group.

Among the consequences of this analysis are an extension of Reilly’s inequality, bounding any eigenvalue of the Laplacian in terms of the mean curvature, and spectral criteria for the immersibility of manifolds in homogeneous spaces.
Scalar parabolic PDEs and braids
Authors: Ghrist R. , Vandervorst R.
Published: January 2009

The comparison principle for scalar second order parabolic PDEs on functions

u
(
t
,
x
)

u(t,x)

admits a topological interpretation: pairs of solutions,

u
1

(
t
,
⋅
)

u^1(t,\cdot )

and

u
2

(
t
,
⋅
)

u^2(t,\cdot )

, evolve so as to not increase the intersection number of their graphs. We generalize to the case of multiple solutions

{

u
α

(
t
,
⋅
)

}

α
=
1

n

\{u^\alpha (t,\cdot )\}_{\alpha =1}^n

. By lifting the graphs to Legendrian braids, we give a global version of the comparison principle: the curves

u
α

(
t
,
⋅
)

u^\alpha (t,\cdot )

evolve so as to (weakly) decrease the algebraic length of the braid.

We define a Morse-type theory on Legendrian braids which we demonstrate is useful for detecting stationary and periodic solutions to scalar parabolic PDEs. This is done via discretization to a finite-dimensional system and a suitable Conley index for discrete braids.

The result is a toolbox of purely topological methods for finding invariant sets of scalar parabolic PDEs. We give several examples of spatially inhomogeneous systems possessing infinite collections of intricate stationary and time-periodic solutions.
Properties and identification of human protein drug targets
Authors: Bakheet Tala M. , Doig Andrew J.
Published: January 2009

Motivation: We analysed 148 human drug target proteins and 3573 non-drug targets to identify differences in their properties and to predict new potential drug targets.

Results: Drug targets are rare in organelles; they are more likely to be enzymes, particularly oxidoreductases, transferases or lyases and not ligases; they are involved in binding, signalling and communication; they are secreted; and have long lifetimes, shown by lack of PEST signals and the presence of N-glycosylation. This can be summarized into eight key properties that are desirable in a human drug target, namely: high hydrophobicity, high length, SignalP motif present, no PEST motif, more than two N-glycosylated amino acids, not more than one O-glycosylated Ser, low pI and membrane location. The sequence features were used as inputs to a support vector machine (SVM), allowing the assignment of any sequence to the drug target or non-target classes with an accuracy in the training set of 96%. We identified 668 proteins (23%) in the non-target set that have target-like properties. We suggest that drug discovery programmes would be more likely to succeed if new targets are chosen from this set or their homologues.

Contact:  andrew.doig@manchester.ac.uk

Supplementary Information:  Supplementary data are available at Bioinformatics online.
The European Heart Failure Self‐care Behaviour scale revised into a nine‐item scale (EHFScB‐9): a reliable and valid international instrument
Authors: Jaarsma Tiny , Årestedt Kristofer Franzén , Mårtensson Jan , Dracup Kathleen , Strömberg Anna
Published: January 2009

Aims

Improved self‐care is the goal of many heart failure (HF) management programmes. The 12‐item European Heart Failure Self‐Care Behaviour Scale (EHFScB scale) was developed and tested to measure patient self‐care behaviours. It is now available in 14 languages. The aim of this study was to further determine reliability and validity of the EHFScB scale.

Methods and results

Data from 2592 HF patients (mean age 73 years, 63% male) from six countries were analysed. Internal consistency was determined by Cronbach's alpha. Validity was established by (1) interviews with HF experts and with HF patients; (2) item analysis; (3) confirmatory factor analysis; and (4) analysing the relationship between the EHFScB scale and scales measuring quality of life and adherence. Internal consistency of the 12‐item scale was 0.77 (0.71–0.85). After factor analyses and critical evaluation of both psychometric properties and content of separate items, a nine‐item version was further evaluated. The reliability estimates for the total nine‐item scale (EHFScB‐9) was satisfactory (0.80) and Cronbach's alpha varied between 0.68 and 0.87 in the different countries. One reliable subscale was defined (consulting behaviour) with a Cronbach's alpha of 0.85. The EHFScB‐9 measures a different construct than quality of life (r = 0.18) and adherence (r = 0.37).

Conclusion

The 12‐item EHFScB scale was revised into the nine‐item EHFScB‐9, which can be used as an internally consistent and valid instrument to measure HF‐related self‐care behaviour.
Role of beta‐blockers in patients admitted for worsening heart failure in a real world setting: data from the Italian Survey on Acute Heart Failure†
Authors: Orso Francesco , Baldasseroni Samuele , Fabbri Gianna , Gonzini Lucio , Lucci Donata , D'Ambrosi Ciro , Gobbi Milva , Lecchi Gabriella , Randazzo Silvia , Masotti Giulio , Tavazzi Luigi , Maggioni Aldo Pietro ,   on behalf of Italian Survey on Acute Heart Failure Investigators
Published: January 2009

Aims

Randomized trials have shown that beta‐blockers (BBs) reduce mortality in chronic heart failure (HF). Less data are available on the role of BBs in patients with acute HF, specifically if BBs should be continued or temporarily withdrawn. The aim of this study was to evaluate the role of BBs on in‐hospital outcomes of patients admitted for worsening HF in a Cardiology setting.

Methods and results

One thousand five hundred and seventy‐two patients enrolled in the Italian Survey on Acute HF were evaluated. According to the BB therapy before and during hospitalization, four groups were defined: group A, no/no (51.6%); group B, no/yes (16.4%); group C, yes/no (9.0%); and group D, yes/yes (23.0%). Groups B and D had a significantly lower in‐hospital mortality rate (group B 1.2%, group D 2.8%, group A 10.1%, and group C 12.1%; P < 0.0001). The association between non‐use or withdrawal of BBs and higher mortality rate was confirmed by the multivariable analysis [group D, reference group; odds ratio (OR) 3.28, 95% confidence interval (CI) 1.47–7.32 and OR 4.20, 95% CI 1.59–11.10 for groups A and C, respectively], whereas no difference was found between groups B and D (OR 0.34, 95% CI 0.07–1.78).

Conclusion

In patients hospitalized for worsening HF, non‐use or discontinuation of BBs was associated with a significant higher mortality.
Novel thermosensitive hydrogel injection inhibits post‐infarct ventricle remodelling
Authors: Wang Tao , Wu De‐Qun , Jiang Xue‐Jun , Zhang Xian‐Zheng , Li Xiao‐Yan , Zhang Jin‐Feng , Zheng Zhao‐Bin , Zhuo Renxi , Jiang Hong , Huang Congxin
Published: January 2009

Aims

Myocardial infarction (MI) remains the commonest cause of cardiac‐related death throughout the world. Adverse cardiac remodelling and progressive heart failure after MI are associated with excessive and continuous damage of the extracellular matrix (ECM). In this study, we hypothesized that implantation of hydrogel into infarcted myocardium could replace the damaged ECM, thicken the infarcted wall, and inhibit cardiac remodelling.

Methods and results

MI was induced in rabbits by coronary artery ligation; 4 days later, 200 µL Dex‐PCL‐HEMA/PNIPAAm gel solution was injected into the infarcted myocardium. Injection of phosphate‐buffered saline served as control. Thirty days after treatment, histological analysis indicated that injection of the biomaterial prevented scar expansion and wall thinning compared with controls. Echocardiography studies showed that injection of hydrogel increased left ventricular ejection fraction and attenuated left ventricular systolic and diastolic dilatation. Haemodynamic analysis demonstrated improved cardiac function following implantation of the hydrogel.

Conclusion

These results suggest that injection of thermosensitive Dex‐PCL‐HEMA/PNIPAAm hydrogel is an effective strategy that prevents adverse cardiac remodelling and dysfunction in MI rabbits.
Cyclophosphamide‐evoked heart failure involves pronounced co‐suppression of cytoplasmic thioredoxin reductase activity and non‐protein free thiol level
Authors: Wang Xufang , Zhang Jinsong , Xu Tongwen
Published: January 2009

Aims

Heart failure is a life‐threatening complication of high‐dose cyclophosphamide (CTX) chemotherapy, and the present study aimed at identifying the mechanism involved in mice.

Methods and results

CTX at 800 mg/kg resulted in heart failure, in which cytoplasmic thioredoxin reductase (TrxR1) activity and non‐protein free thiol (NPFT) level were suppressed by 90 and 62%, respectively. The combination of 350 mg/kg CTX and the glutathione synthesis inhibitor buthionine sulfoximine (BSO) also evoked heart failure, in which TrxR1 activity and NPFT level were suppressed by 66 and 62%, respectively. NPFT depletion alone by BSO did not cause cardiac toxicity. CTX at 350 mg/kg alone also did not cause cardiac toxicity, even though it suppressed TrxR1 activity by 68%. Previous studies have shown that half inactivation of TrxR1 in tumour, bladder, and kidneys was associated with toxicological consequences. Cardiac TrxR1 is dispensable, but cardiac cytoplasmic thioredoxin (Trx1) is essential. The potential uncoupling between TrxR1 and Trx1 may explain why there is no cardiac toxicity following TrxR1 inhibition. However, TrxR1 inactivation may still play a role in CTX‐evoked heart failure because inactivated TrxR1 gains cytotoxic function, which may engender noticeable toxicity when massive NPFT is deleted.

Conclusion

CTX‐evoked heart failure involves pronounced co‐suppression of TrxR1 activity and NPFT level.
Transplantation of mesenchymal stem cells within a poly(lactide‐co‐ɛ‐caprolactone) scaffold improves cardiac function in a rat myocardial infarction model
Authors: Jin Jiyong , Jeong Sung In , Shin Young Min , Lim Kwang Suk , Shin Heung soo , Lee Young Moo , Koh Hyun Chul , Kim Kyung‐Soo
Published: January 2009

Aims

Cardiac tissue engineering has been proposed as an appropriate method to repair myocardial infarction (MI). Evidence suggests that a cell with scaffold combination was more effective than a cell‐only implant. Nevertheless, to date, there has been no research into elastic biodegradable poly(lactide‐co‐ε‐caprolactone) (PLCL) scaffolds. The aim of this study was to investigate the effect of mesenchymal stem cells (MSCs) with elastic biodegradable PLCL scaffold transplants in a rat MI model.

Methods and results

Ten days after inducing MI through the cryoinjury method, a saline control, MSC, PLCL scaffold, or MSC‐seeded PLCL scaffold was transplanted onto the hearts. Four weeks after transplantation, cardiac function and histology were evaluated. Transplanted MSCs survived and differentiated into cardiomyocytes in the injured region. Left ventricular ejection fraction in the MSC + PLCL group increased by 23% compared with that in the saline group; it was also higher in the MSC group. The infarct area in the MSC + PLCL group was decreased by 29% compared with that in the saline group; it was also reduced in the MSC group.

Conclusion

Mesenchymal stem cells plus PLCL should be an excellent combination for cardiac tissue engineering.
Rationale and design of the Karolinska‐Rennes (KaRen) prospective study of dyssynchrony in heart failure with preserved ejection fraction
Authors: Donal Erwan , Lund Lars H. , Linde Cecilia , Edner Magnus , Lafitte Stéphane , Persson Hans , Bauer Fabrice , Öhrvik John , Ennezat Pierre‐Vladimir , Hage Camilla , Löfman Ida , Juilliere Yves , Logeart Damien , Derumeaux Geneviève , Gueret Pascal , Daubert Jean‐Claude
Published: January 2009

Aims

Heart failure with preserved ejection fraction (HFPEF) is common but not well understood. Electrical dyssynchrony in systolic heart failure is harmful. Little is known about the prevalence and the prognostic impact of dyssynchrony in HFPEF.

Methods and results

We have designed a prospective, multicenter, international, observational study to characterize HFPEF and to determine whether electrical or mechanical dyssynchrony affects prognosis. Patients presenting with acute heart failure (HF) will be screened so as to identify 400 patients with HFPEF. Inclusion criteria will be: acute presentation with Framingham criteria for HF, left ventricular ejection fraction ≥ 45%, brain natriuretic peptide (BNP) > 100 pg/mL or NT‐proBNP > 300 pg/mL. Once stabilized, 4–8 weeks after the index presentation, patients will return and undergo questionnaires, serology, ECG, and Doppler echocardiography. Thereafter, patients will be followed for mortality and HF hospitalization every 6 months for at least 18 months. Sub‐studies will focus on echocardiographic changes from the acute presentation to the stable condition and on exercise echocardiography, cardiopulmonary exercise testing, and serological markers.

Conclusion

KaRen aims to characterize electrical and mechanical dyssynchrony and to assess its prognostic impact in HFPEF. The results might improve our understanding of HFPEF and generate answers to the question whether dyssynchrony could be a target for therapy in HFPEF.
Isoproterenol‐induced heart failure in the rat is associated with nitric oxide‐dependent functional alterations of cardiac function
Authors: Krenek Peter , Kmecova Jana , Kucerova Dana , Bajuszova Zuzana , Musil Peter , Gazova Andrea , Ochodnicky Peter , Klimas Jan , Kyselovic Jan
Published: January 2009

Aims

The role of nitric oxide (NO) in heart failure (HF) is complex and remains controversial. We tested the hypothesis that the role of NO in isolated atria and cardiomyocytes is altered in isoproterenol‐induced HF.

Methods and results

Rats received isoproterenol (ISO, 5 mg/kg/day, intraperitoneally) or vehicle for 1 week. Haemodynamic parameters were obtained by left ventricular catheterization. Effects of NOS inhibition on isolated atria and on electrically paced left ventricular myocytes were determined. Additionally, expressions of nitric oxide synthases and their allosteric modulators hsp90, caveolin‐1, and caveolin‐3 proteins in the left ventricles were measured. ISO increased left ventricular mass by 33% and decreased indices of left ventricular systolic and diastolic function dp/dtminand dp/dtmax(bothP< 0.05). Isolated atria from HF rats had a lower spontaneous beating rate (P< 0.05). NOS inhibition by L‐NAME increased basal frequency and attenuated the positive chronotropic effect of beta‐adrenergic stimulation in the HF group (P< 0.05). Ventricular myocytes from failing hearts had impaired cell shortening. L‐NAME decreased contractility of control, but not failing myocytes. Left ventricular expressions of eNOS, hsp90, iNOS, but not nNOS or caveolins, were increased.

Conclusion

Despite the increased capacity for NO synthesis in isoproterenol‐induced HF, NO does not sustain contractility of failing myocytes. NO may contribute to the decreased basal heart rate and it may accelerate beta‐adrenergic stimulation of chronotropy.
A randomized trial of the addition of home‐based exercise to specialist heart failure nurse care: the Birmingham Rehabilitation Uptake Maximisation study for patients with Congestive Heart Failure (BRUM‐CHF) study
Authors: Jolly Kate , Taylor Rod S. , Lip Gregory Y.H. , Davies Mick , Davis Russell , Mant Jonathan , Singh Sally , Greenfield Sheila , Ingram Jackie , Stubley Jane , Bryan Stirling , Stevens Andrew
Published: January 2009

Aims

Supervised exercise can benefit selected patients with heart failure, however the effectiveness of home‐based exercise remains uncertain. We aimed to assess the effectiveness of a home‐based exercise programme in addition to specialist heart failure nurse care.

Methods and results

This was a randomized controlled trial of a home‐based walking and resistance exercise programme plus specialist nurse care (n= 84) compared with specialist nurse care alone (n= 85) in a heart failure population in the West Midlands, UK. Primary outcome: Minnesota Living with Heart Failure Questionnaire (MLwHFQ) at 6 and 12 months. Secondary outcomes: composite of death, hospital admission with heart failure or myocardial infarction; psychological well‐being; generic quality of life (EQ‐5D); exercise capacity. There was no statistically significant difference between groups in the MLwHFQ at 6 month (mean, 95% CI) (−2.53, −7.87 to 2.80) and 12 month (−0.55, −5.87 to 4.76) follow‐up or secondary outcomes with the exception of a higher EQ‐5D score (0.11, 0.04 to 0.18) at 6 months and lower Hospital Anxiety and Depression Scale score (−1.07, −2.00 to −0.14) at 12 months, in favour of the exercise group. At 6 months, the control group showed deterioration in physical activity, exercise capacity, and generic quality of life.

Conclusion

Home‐based exercise training programmes may not be appropriate for community‐based heart failure patients.
Self‐assessment of health status is associated with inflammatory activation and predicts long‐term outcomes in chronic heart failure
Authors: Parissis John T. , Nikolaou Maria , Farmakis Dimitrios , Paraskevaidis Ioannis A. , Bistola Vassiliki , Venetsanou Koula , Katsaras Dimitrios , Filippatos Gerasimos , Kremastinos Dimitrios T.
Published: January 2009

Aims

Clinicians lack a generally accepted means for health status assessment in chronic heart failure (CHF). We investigated the correlation between health status and inflammation burden as well as its long‐term prognostic value in CHF outpatients.

Methods and Results

Kansas City Cardiomyopathy Questionnaires (KCCQ) were completed by 137 CHF outpatients (aged 64 ± 12 years, mean ejection fraction 27 ± 7%). Inflammatory markers [interleukin (IL)‐6, IL‐10, TNF‐α, soluble Fas, Fas ligand, ICAM‐1, VCAM‐1], plasma B‐type natriuretic peptide (BNP), 6 min walk test (6MWT), Zung self‐rating depression scale, and Beck Depression Inventory were also assessed. Patients were followed for major cardiovascular events (death or hospitalization for disease progression) for up to 250 days. Patients with worse KCCQ‐summary (KCCQ‐s < 50) score had lower 6MWT (P < 0.05), and higher BNP (P < 0.05) and pro‐inflammatory markers (P < 0.05) than those with KCCQ‐s ≥ 50. Worse health status was also associated with shorter event‐free survival (115 ± 12 days for KCCQ‐s < 50 vs. 214 ± 15 days for KCCQ‐s ≥ 50, P = 0.0179). Separating patients according KCCQ‐functional score (KCCQ‐f, cut‐off 50) showed similar results. In multivariate Cox regression analysis, only LVEF (HR = 0.637, 95% CI 0.450–0.900, P = 0.011) and KCCQ‐f (HR = 0.035, 95% CI 0.002–0.824, P = 0.037) were independent predictors of event‐free survival at 250 days.

Conclusion

KCCQ‐s reflects neurohormonal and inflammatory burden in CHF. Among studied questionnaires, only KCCQ‐f is an independent predictor of long‐term event‐free survival in CHF.
Rapid left ventricular recovery after cabergoline treatment in a patient with peripartum cardiomyopathy
Authors: de Jong Jonas S.S.G. , Rietveld Kirsten , van Lochem Laura T. , Bouma Berto J.
Published: January 2009

The aetiology of peripartum cardiomyopathy (PPCM) is still largely unknown. Recent evidence suggests that the breakdown products from prolactin can induce cardiomyopathy. Prolactin secretion can be reduced with bromocriptine which had beneficial effects in a small study. We present a case of a patient with PPCM who received cabergoline, a strong and long lasting antagonist of prolactin secretion. Following treatment, her prolactin levels dropped swiftly. N‐terminal pro‐BNP levels, which had remained high up to that point, dropped within 1 day (7006 to 4408 pg/mL). Echocardiographic left ventricular ejection fraction recovered from 26% on Day 4 postpartum to 32% and later 47% on Days 2 and 5 after cabergoline treatment. To our knowledge, this is the first description of a case of PPCM in which cabergoline was administered.
The cyclic guanosine monophosphate/B‐type natriuretic peptide ratio and mortality in advanced heart failure
Authors: Lourenço Patrícia , Araújo José Paulo , Azevedo Ana , Ferreira António , Bettencourt Paulo
Published: January 2009

Aims

Attenuation of the effects of natriuretic peptides has been demonstrated in animal models but studies in humans are scarce, particularly concerning renal attenuation. We investigated the attenuation of B‐type natriuretic peptide (BNP) in chronic advanced heart failure (HF).

Methods and results

We included 62 outpatients with HF and severe left ventricular systolic dysfunction. Cases had at least one hospital admission or emergency department visit for acute HF in the previous year and were in NYHA class III/IV despite optimized therapy. The individual age‐ and sex‐matched controls were symptomatically controlled (NYHA I and II). We collected 24 h urine and a blood sample from all patients. Plasma BNP and plasma (pcGMP) and urine cyclic guanosine monophosphate (ucGMP) were measured. Patients were followed for 3 months for hospital admission or all‐cause death. ucGMP to plasma BNP (ucGMP/BNP) ratio was attenuated in cases vs. controls [median (IQR): 8354 (4293–16 456) vs. 12 693 (6896–22 851)]. There were no differences in pcGMP to BNP (pcGMP/BNP) ratio or urine cGMP excretion. Patients with worse outcome had lower pcGMP/BNP [260 (86–344) vs. 381 (244–728) in patients without adverse outcome events] and lower ucGMP/BNP [4146 (2207–9363) vs. 10 922 (7495–19 971)].

Conclusion

Renal NP's second messenger production is attenuated in advanced HF. Patients with worse outcome have lower ucGMP/BNP and pcGMP/BNP ratios.
Immunological mechanisms of pentoxifylline in chronic heart failure
Authors: Shaw Steven M. , Shah Mohammed K.H. , Williams Simon G. , Fildes James E.
Published: January 2009

The progressive syndrome of chronic heart failure (CHF) represents a common disease pathway that may be derived from a host of varying insults (including myocardial ischaemia and infarction, hypertension, viral infection, pregnancy, etc). Despite this multifarious aetiology, a common phenomena observed in CHF patients is elevated levels of tumour necrosis factor (TNF)‐α. This has led to the widespread concept that TNF‐α is directly involved in the pathophysiology of CHF and as such, attempts have been made to inhibit TNF‐α production in this cohort. However, to date, there have been no clear beneficial effects from TNF‐α inhibition and indeed trials of direct anti‐TNF therapy have provoked worsening of clinical outcomes. Conversely, a possible exception is pentoxifylline (PTX), a putative TNF‐α inhibitor with possible (but ill‐defined) vasodilatory properties. Several small clinical trials assessing the use of PTX in CHF have suggested beneficial effects on multiple surrogate clinical markers. Interestingly, these trials failed to show a concordant effect on circulating TNF despite the clinical improvement, suggesting other key beneficial properties of this novel agent. This review article provides an insight into the potential beneficial mode of the action of PTX in CHF and calls for more investigation of this interesting agent.
Inflammation as a therapeutic target in heart failure? A scientific statement from the Translational Research Committee of the Heart Failure Association of the European Society of Cardiology
Authors: Heymans Stephane , Hirsch Emilio , Anker Stefan D. , Aukrust Pal , Balligand Jean‐Luc , Cohen‐Tervaert Jan W. , Drexler Helmut , Filippatos Gerasimos , Felix Stephan B. , Gullestad Lars , Hilfiker‐Kleiner Denise , Janssens Stefan , Latini Roberto , Neubauer Gitte , Paulus Walter J. , Pieske Burkert , Ponikowski Piotr , Schroen Blanche , Schultheiss Heinz‐Peter , Tschöpe Carsten , van Bilsen Marc , Zannad Faiez , McMurray John , Shah Ajay M.
Published: January 2009

The increasing prevalence of heart failure poses enormous challenges for health care systems worldwide. Despite effective medical interventions that target neurohumoral activation, mortality and morbidity remain substantial. Evidence for inflammatory activation as an important pathway in disease progression in chronic heart failure has emerged in the last two decades. However, clinical trials of ‘anti‐inflammatory’ therapies (such as anti‐tumor necrosis factor‐α approaches) have to date failed to show benefit in heart failure patients. The Heart Failure Association of the European Society of Cardiology recently organized an expert workshop to address the issue of inflammation in heart failure from a basic science, translational and clinical perspective, and to assess whether specific inflammatory pathways may yet serve as novel therapeutic targets for this condition. This consensus document represents the outcome of the workshop and defines key research questions that still need to be addressed as well as considering the requirements for future clinical trials in this area.
Clinical trials update from the Heart Failure Society of America and the American Heart Association meetings in 2008: SADHART‐CHF, COMPARE, MOMENTUM, thyroid hormone analogue study, HF‐ACTION, I‐PRESERVE, β‐interferon study, BACH, and ATHENA
Authors: Coletta Alison P. , Clark Andrew L. , Cleland John G.F.
Published: January 2009

This article provides information and a commentary on trials relevant to the pathophysiology, prevention, and treatment of heart failure presented at the Heart Failure Society of America and the American Heart Association meetings in 2008. Unpublished reports should be considered as preliminary, as analyses may change in the final publication. (i) SADHART‐CHF showed no difference in outcome for heart failure patients with depression treated with sertraline compared with placebo. (ii) A controlled release carvedilol formulation showed similar LV haemodynamic effects to the standard carvedilol formulation in the COMPARE study. (iii) A post hoc analysis of the MOMENTUM study suggested that patients with less severe heart failure may be more likely to benefit from a continuous aortic flow augmentation device. (iv) A thyroid hormone analogue was poorly tolerated in patients with heart failure. (v) HF‐ACTION showed that exercise training is safe and offers modest clinical benefits in patients with heart failure. (vi) Irbesartan failed to improve outcomes in patients with preserved ejection fraction in the I‐PRESERVE study. (vii) A phase II study of beta‐interferon administration in patients with dilated cardiomyopathy showed encouraging results. (viii) The BACH study showed that mid‐regional pro‐adrenomedullin was more accurate than BNP or NT‐proBNP at predicting outcome at 90 days in patients with acute heart failure. (ix) A secondary analysis from ATHENA showed a reduction in cardiovascular hospitalizations and strokes for patients with atrial fibrillation receiving dronedarone compared with placebo.
Interexaminer Variance of Median Nerve Compound Muscle Action Potential Measurements in Hand Position With and Without Fixation in Plaster
Authors: Higuchi Keiichi , Narita Yugo , Kuzuhara Shigeki
Published: January 2009

Objectives:

We examined how hand fixation affects interexaminer variance in measuring compound muscle action potential (CMAP) during nerve conduction studies of the median nerve.

Methods:

Subjects comprised 6 experienced examiners [1 woman and 5 men; mean (SD) age, 38.3 ± 8.5 years; range, 28-46 years]. The standardized median nerve motor conduction setting was used for electromyography. The mean of 5 serial stimulations was taken as 1 examination for each subject. Distal latency, conduction velocity, and peak-to-peak amplitude of CMAP were measured as parameters. Subjects were examined without hand fixation and with hands fixed in prepared plaster molds.

Results:

Fixation yielded significantly decreased coefficient of variance for CMAP amplitude (5.0% ± 3.4%) compared with measurement without fixation (8.4% ± 3.7%; P = 0.028). No differences in distal latencies or conduction velocities were evident between fixation and nonfixation.

Conclusions:

This study provides quantitative evidence for empirical observations that hand fixation might decrease CMAP variability in median nerve studies.
Safety of Liquid Intravenous Immunoglobulin for Neuroimmunologic Disorders in the Home Setting: A Retrospective Analysis of 1085 Infusions
Authors: Rigas Michael , Tandan Rup , Sterling Robert J
Published: January 2009

Objective:

To examine the overall safety of intravenous immunoglobulin (IVIG) administered according to a clinically defined, home-based therapeutic regimen in patients with neuroimmunologic diseases.

Methods:

A total of 1085 infusions of a new liquid IVIG 10% preparation were administered to 70 patients diagnosed with neuroimmunologic diseases over a 9-month period. These infusions were retrospectively reviewed for safety and tolerability.

Results:

A very favorable adverse effect (AE) rate (4.7%) was calculated over a wide range of doses (0.9-2.14 g/kg). There were no serious AEs reported, even among patients naive to IVIG therapy. Of 51 nonserious AEs, 53% occurred in 5 patients.

Conclusions:

The results of this review of 1085 high-dose liquid IVIG infusions using a closely monitored, yet highly flexible, home-based therapeutic regimen indicate a very favorable tolerability profile in patients with neuroimmunologic disorders, even in those who were new to IVIG therapy.
Peripheral Nerve Vasculitis Presenting as Complex Regional Pain Syndrome
Authors: Ramchandren Sindhu , Chaudhry Vinay , Hoke Ahmet , Murinson Beth B , Cornblath David R , Treisman Glenn J , Griffin John W
Published: January 2009

Objective:

To report the clinical, electrodiagnostic, and pathologic findings in 3 patients who presented with complex regional pain syndrome as their primary manifestation of peripheral nerve vasculitis.

Design:

Case series.

Setting:

Outpatient clinic in a tertiary care academic medical center.

Patients:

Patient 1 was a 39-year-old woman with a 9-year history of non-length-dependent severe burning pain and swelling in her extremities. Patient 2 was a 67-year-old man with a 2-year history of severe burning pain and swelling in an extremity after a fall. Patient 3 was a 74-year-old man with a 6-month history of severe allodynic pain and atrophy of the right hand after a viral illness

Results:

In all 3 cases, clinical and electrodiagnostic testing were suggestive of multiple mononeuropathies. Nerve biopsy either confirmed vasculitis (patient 1) or was suggestive of angiopathy (patients 2 and 3). Immunomodulative therapy led to marked clinical improvement in all 3 cases.

Conclusions:

To our knowledge, this is the first report demonstrating that the inflammatory nerve injury seen with peripheral nerve vasculitis can result in complex regional pain syndrome. Clinical and electrodiagnostic assessments can help in the identification and management of these patients.
Electrodiagnostic and Clinical Aspects of Guillain-Barré Syndrome: An Analysis of 142 Cases
Authors: Deepak Gupta , Muraleedharan Nair , Baheti Neeraj N , Sarma Sankara P , Abraham Kuruvilla
Published: January 2009

Background:

The incidence of Guillain-Barré syndrome (GBS) and its subtypes varies throughout the world.

Objective and Methods:

We present a retrospective analysis of 142 GBS cases, treated at our center, aimed at classifying GBS electrophysiologically, to study the sequential electrophysiological changes in cases with acute inflammatory demyelinating polyradiculoneuropathy (AIDP), and to look for any clinical and cerebrospinal fluid parameters that can also help in distinguishing the subtypes.

Results:

One hundred twenty-one (85.2%) cases had AIDP, 15 (10.6%) had acute motor axonal neuropathy, and 6 (4.2%) were unclassifiable.

Conclusions:

Motor conduction blocks and temporal dispersion could be observed from days 3 and 5 onward, respectively. Progression of motor conduction slowing in AIDP was most impressive in the median nerves. Varying affection of deep tendon reflexes, cranial nerves, and cerebrospinal fluid albuminocytological dissociation can also help make a distinction between AIDP and acute motor axonal neuropathy. Sural sparing, a marker of demyelinating neuropathy, is more commonly seen in later than in early stages of AIDP.
Steroid-Responsive Paraneoplastic Demyelinating Neuropathy and Myelopathy Associated With Breast Carcinoma
Authors: Rajabally Yusuf A , Qaddoura Bassel , Abbott Richard J
Published: January 2009

Paraneoplastic myeloneuropathy has rarely been reported with breast cancer. We report the case of a 59-year-old woman who presented with a peripheral neuropathy and cranial involvement and later developed a myelopathy. The neuropathy was found to be electrophysiologically and histologically demyelinating in nature. Magnetic resonance imaging studies failed to identify any structural brain or spinal cord abnormalities. The patient was diagnosed with breast carcinoma 4 months after initial presentation and underwent resective surgery, radiotherapy, and hormonotherapy. Paraneoplastic antibodies (anti-Hu, anti-Yo, anti-Ri, anti-CV2, anti-Ma, and anti-amphiphysin) were all negative. Her condition did not progress further after cancer treatment. Partial neurologic improvement occurred with oral steroid therapy, with subsequent deterioration on treatment withdrawal.