bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of basic surgical trainees: can we do more?
Authors: Somaseker K , Shankar J , Conway K P , Foster M E , Lewis M H
Published: June 2003

Introduction

Changes to surgical training and reduction of junior doctors’ working hours has resulted in trainees spending less time in surgical specialties before becoming eligible to apply for specialist registrar posts. A high quality basic surgical training programme is needed to improve the competence of trainees during their shortened period, an essential part of which is to conduct a formal assessment at the end of each training post and regular appraisals during their period of training.

Aims

To analyse the existing practice with regard to conducting assessment and appraisals for basic surgical trainees in the South East Wales region.

Methods

A questionnaire was sent to all the basic surgical trainees in the South East Wales region.

Results

A total of 52 questionnaires were sent out and 44 (84%) were returned. Four candidates were in the first post of their rotation, and were therefore excluded from the study. Nine of the 40 trainees (23%) did not have an assessment in one or more of their posts. There are 17 senior house officer posts available in general surgery in the rotation. Of the 31 “six month” episodes spent in these 17 posts, 27 (87%) underwent an assessment, 12 of the 17 (70%) episodes in trauma and orthopaedics (12 available posts) were assessed, and 31 of the 35 (88%) episodes in accident and emergency (eight available posts) underwent an assessment. Twenty eight of the 40 trainees (70%) did not undergo regular appraisals during the majority of their posts. Only 30%–50% of episodes spent in general surgery, orthopaedics, and accident and emergency underwent appraisals. The majority of the episodes spent in the other surgical specialties (12 posts available in total) had formal assessment and regular appraisals except for urology in which two of seven episodes underwent assessment and one underwent an appraisal. Twelve candidates (30%) expressed the view that operative experience and technical skills must form part of their assessment. Eight trainees (20%) felt that they needed more help from tutors with regard to career advice, preparation of curriculum vitae, and interview techniques for specialist registrar posts. Eight trainees mentioned that they had discussed unsatisfactory posts with their tutors but were not aware of any changes made to these posts.

Conclusions

This study has shown that the formal assessment of basic surgical trainees at the end of each training post has to improve further. The existing practice of conducting regular appraisals for the trainees is grossly inadequate. There appears to be a need for formulating guidelines for conducting such appraisals, which would help to improve practice in the future.
How valuable is ascitic cytology in the detection and management of malignancy?
Authors: Karoo R O S , Lloyd T D R , Garcea G , Redway H D , Robertson G S R
Published: June 2003

Introduction

Ascitic cytology is often requested in the early stages of ascitic assessment. A review of this practice in a major English teaching hospital is presented.

Method

Patients were retrospectively identified using the histopathology and patient administration system between January 1999 and May 2001.

Results

Of 276 samples sent for assessment 35 cases were found to be negative when on further review an intra-abdominal malignancy was present. The malignancy was diagnosed using a radiological modality. The sensitivity of ascitic cytology was found to be 60% with 100% specificity. A delay of up to five days could be incurred awaiting the cytology results before further radiological examinations were undertaken.

Conclusion

Too much hope is placed on ascitic cytology to provide the diagnosis at the expense of other investigations. It is recommended that the initial assessment should concentrate on history, examination, and basic tests on ascitic fluid to assess the serum-ascites albumin gradient. Ovarian malignancy is the only tumour type yielding a significant rate of detection from cytology with some prognostic impact. Results should not be awaited before abdominal ultrasound is undertaken. This more directed practice would help reduce unnecessary workload for the pathologist and has resource implications.
Ventricular fibrillation during electrical cardioversion of pre-excited atrial fibrillation
Authors: Adlam D , Azeem T
Published: June 2003

The Wolff-Parkinson-White syndrome can rarely present with pre-excited atrial fibrillation. In this condition the short refractory period of the accessory pathway can lead to rapid atrioventricular conduction. There is then a danger that at high heart rates the irregular broad complex tachycardia that results can deteriorate into ventricular fibrillation. The initial management of patients presenting in pre-excited atrial fibrillation requires cardioversion to sinus rhythm. This can be performed by DC cardioversion or pharmacological means. This paper describes the case of a patient presenting in pre-excited atrial fibrillation where electrical DC cardioversion lead to transient iatrogenic ventricular fibrillation.
Development of oligonucleotide primers for the specific PCR-based detection of the most frequentEnterobacteriaceaespecies DNA usingwecgene templates
Authors: Bayardelle Paul , Zafarullah Muhammad
Published: June 2003

Oligonucleotide primers were designed for the PCR-based detection of the wec gene cluster involved in the biosynthetic pathway leading to the production of enterobacterial common antigen (ECA). Escherichia coli DNA was detected using wec A, wec E, and wec F gene primers. The wec A primers were specific for E. coli. The wec E and wec F primers enabled the detection of the most frequent species of the Enterobacteriaceae found in blood and urine specimens as well as in water. The sensitivity of the assay was approximately 1.2 × 102bacteria/mL of water. Thus, these primers represent an important step in the molecular diagnosis of major Enterobacteriaceae infections. Their role in the routine testing of contamination in drinking water and food may prove to be very useful. The DNA of Enterobacteriaceae species is detected in a first step PCR, followed by specific identification of important pathogens like E. coli O157, Shigella spp., Salmonella spp., and Yersinia spp.Key words: Enterobacteriaceae, wec gene, enterobacterial common antigen, PCR, biological fluids.
Purification and characterization of an extracellular exochitinase, β-N-acetylhexosaminidase, from the fungal mycoparasiteStachybotrys elegans
Authors: Taylor Greg , Jabaji-Hare Suha , Charest Pierre M , Khan Wajahatullah
Published: June 2003

The mycoparasite Stachybotrys elegans produces two exo- and one endo-acting chitinases when grown on chitin. We purified to homogeneity one of the exo-acting chitinases, β-N-acetylhexosaminidase and partially characterized its physical and biochemical properties. The native enzyme has a molecular mass of 120 kDa when determined by gel filtration and 68 kDa by sodium dodecyl sulfate  polyacrylamide gel electrophoresis indicating that the native protein probably occurs as a dimer in solution. The purified β-N-acetylhexosaminidase is most active at pH 5.0 and 40°C and hydrolyzes the ρ-nitrophenyl-N-acetyl-β-D-glucosaminide with apparent Kmof 84.6 µM. Polyclonal antibodies raised against the 68-kDa β-N-acetylhexosaminidase (NAG-68) indicated that the antibody is highly specific and recognizes the protein in crude filtrate preparation. This suggests that the protein is a not a proteolytic product of another protein. Western blot analysis showed that the activity of NAG-68 was induced when S. elegans was grown on purified cell wall fragments of its host, Rhizoctonia solani, as well as during antagonistic interaction of the mycoparasite and host when both were grown on synthetic medium with or without supplemental carbon source.Key words: chitinases, protein purification, mycoparsite, Rhizoctonia solani.
The pathway of dephosphorylation of myo-inositol hexakisphosphate by phytate-degrading enzymes of different Bacillus spp.
Authors: Greiner Ralf , Farouk Adelazim , Alminger Marie Larsson , Carlsson Nils-Gunnar
Published: June 2003

The pathway of dephosphorylation of myo-inositol hexakisphosphate by the phytate-degrading enzymes of Bacillus subtilis 168, Bacillus amyloliquefaciens ATCC 15841, and Bacillus amyloliquefaciens 45 was established using a combination of high-performance ion chromatography analysis and kinetic studies. The data demonstrate that all the Bacillus phytate-degrading enzymes under investigation dephosphorylate myo-inositol hexakisphosphate by sequential removal of phosphate groups via two independent routes; the routes proceed via D-Ins(1,2,4,5,6)P5 to Ins(2,4,5,6)P4 to finally Ins(2,4,6)P3 or D-Ins(2,5,6)P3 and via D-Ins(1,2,4,5,6)P5 to D-Ins(1,2,5,6)P4 to finally D-Ins(1,2,6)P3. The resulting myo-inositol trisphosphate D-Ins(1,2,6)P3 was degraded via D-Ins(2,6)P2 to finally Ins(2)P after prolonged incubation times in combination with increased enzyme concentration. Key words: Bacillus spp., myo-inositol phosphate isomers, phytase, phytate degradation.
Properties of a hydrophobin isolated from the mycoparasitic fungus Verticillium fungicola
Authors: Calonje Myriam , Bernardo Dolores , Novaes-Ledieu Monique , Mendoza Concepción García
Published: June 2003

Verticillium fungicola, isolated from Agaricus bisporus (commercial mushroom), produced significant extracellular hydrophobin when grown for 7 days in a static liquid culture of synthetic minimal medium. The hydrophobin was purified by precipitation with ammonium sulphate (80% saturation), Sephadex G-100 gel filtration, and hydroxyapatite column chromatography. The purified protein yielded a single band in polyacrylamide gel electrophoresis under native conditions, with an apparent molecular mass of 70 ± 4 kDa, and also another single band in SDSPAGE, with a molecular mass of 7 ± 3 kDa. Molecular mass determined with matrix-assisted laser desorption ionizationmass spectrometry (MALDIMS) resulted in 7563.9 m/z. The same protein was extracted from the V. fungicola mycelium. Analysis of the amino acid composition revealed the presence of about 50% hydrophobic residues, detecting at least six cysteines, evaluated as cystines, and no free sulfhydryl groups. The protein did not show any glycosylation. On the basis of similarities in hydropathy patterns and solubility characteristics, V. fungicola hydrophobin can be included as a new member of Class II hydrophobins.Key words: Verticillium fungicola, Agaricus bisporus, hydrophobin, mycoparasitism.
A HIGHLY ACCURATE BOOTSTRAPPING ALGORITHM FOR WORD SENSE DISAMBIGUATION
Authors: MIHALCEA RADA F. , MOLDOVAN DAN I.
Published: June 2003

In this paper, we present a bootstrapping algorithm for Word Sense Disambiguation which succeeds in disambiguating a subset of the words in the input text with very high precision. It uses WordNet and a semantic tagged corpus, for the purpose of identifying the correct sense of the words in a given text. The bootstrapping process initializes a set of ambiguous words with all the nouns and verbs in the text. It then applies various disambiguation procedures and builds a set of disambiguated words: new words are sense tagged based on their relation to the already disambiguated words, and then added to the set. This process allows us to identify, in the original text, a set of words which can be disambiguated with high precision; 55% of the verbs and nouns are disambiguated with an accuracy of 92%.
GENETIC ALGORITHMS AND REINFORCEMENT LEARNING FOR THE TACTICAL FIXED INTERVAL SCHEDULING PROBLEM
Authors: SANTOS EUGENE , ZHONG XIAOMIN
Published: June 2003

Discrete optimization problems are usually NP hard. The structural characteristics of these problems significantly dictate the solution landscape. In this paper, we explore a structure-based approach to solving these kinds of problems. We use a reinforcement learning system to adaptively learn the structural characteristics of the problem, hereby decomposing the problem into several subproblems. Based on these structural characteristics, we develop a Genetic Algorithm by using structural operations to recombine these subproblems together to solve the problem. The reinforcement learning system directs the GA. We test our algorithm on the Tactical Fixed Interval Scheduling Problem(TFISP) which is the problem of determining the minimum number of parallel non-identical machine such that a feasible schedule exists for a given set of jobs. This work continues our work in exploiting structure for optimization.
DEVELOPING A TOOL FOR UNIFIED COGNITIVE MODELING USING A MODEL OF LEARNING AND UNDERSTANDING IN YOUNG CHILDREN
Authors: HANNON CHARLES , COOK DIANE J.
Published: June 2003

To reduce the complexity of studying a parallel mechanism for natural language learning and understanding which supports both utterance and discourse processing, we propose a computational model demonstrating the performance of a young language user just starting to construct one and two word utterances. This model is constructed using discoveries from both connectionism and symbolic research which guided the construction of our own cognitive modeling system. This system consists of 1) a cognitive theory, 2) a cognitive and a computational architecture, and 3) the support environment necessary to construct concurrent symbolic-based cognitive models using a multi-agent environment. After providing the discourse performance of the resulting model, we also address the pragmatic consideration of building and supporting the resulting modeling system and language model on a cluster of SMP computers.
CONSTRUCTING MODULAR HYBRID RULE BASES FOR EXPERT SYSTEMS
Authors: HATZILYGEROUDIS I. , PRENTZAS J.
Published: June 2003

Neurules are a kind of hybrid rules integrating neurocomputing and production rules. Each neurule is represented as an adaline unit. Thus, the corresponding neurule base consists of a number of autonomous adaline units (neurules). Due to this fact, a modular and natural knowledge base is constructed, in contrast to existing connectionist knowledge bases. In this paper, we present a method for generating neurules from empirical data. To overcome the difficulty of the adaline unit to classify non-separable training examples, the notion of 'closeness' between training examples is introduced. In case of a training failure, two subsets of 'close' examples are produced from the initial training set and a copy of the neurule for each subset is trained. Failure of training any copy, leads to production of further subsets as far as success is achieved.
ADVANCES IN ADAPTIVE PROTOTYPE WEIGHTING AND SELECTION
Authors: NOCK R. , SEBBAN M.
Published: June 2003

The noise intolerance and the storage requirements of Nearest-Neighbor-based algorithms are the two main obstacles to their use for solving complex classification tasks. From the beginning of the 70's (with Hart and Gates), many methods have been proposed for dealing with these problems, by eliminating mislabeled instances, and selecting relevant prototypes. These models often have the distinctive feature of optimizing during the process the accuracy. In this paper, we present a new original approach which adapts the properties of boosting (which optimizes an other criterion) to the prototype selection field. While in a standard boosting algorithm the final classifier combines a set of weak hypotheses, where each one is a classifier built according to a given distribution over the training data, we defined in our approach each weak hypothesis as a single weighted prototype. The distribution update (a key step of boosting) and the criterion optimized during the process are slightly modified to allow an efficient adaptation of boosting to the prototype selection field.

In order to show the interest of our new algorithm, called PSBOOST, we achieved a wide experimental study, comparing our procedure with the state-of-the-art prototype selection algorithms. Taking into account many performance measures, such as storage reduction, noise tolerance, generalization accuracy and learning speed, we can claim that PSBOOST seems to be very efficient by providing a good balance between all these performance measures. A statistical analysis is presented to validate all the results.
OVERRIDING THE EXPERTS: A FUSION METHOD FOR COMBINING MARGINAL CLASSIFIERS
Authors: HAPPEL MARK D. , BOCK PETER
Published: June 2003

The design of an optimal Bayesian classifier for multiple features is dependent on the estimation of multidimensional joint probability density functions and therefore requires a design sample size that increases exponentially with the number of dimensions. A method was developed that combines classification decisions from marginal density functions using an additional classifier. Unlike voting methods, this method can select a more appropriate class than the ones selected by the marginal classifiers, thus "overriding" their decisions. It is shown that this method always exhibits an asymptotic probability of error no worse than the probability of error of the best marginal classifier.
AN AUTOMATED THEOREM PROVER BASED ON CONNECTION TABLEAU CALCULI WITH DISJUNCTIVE CONSTRAINTS
Authors: IBENS ORTRUN , FUCHS MARC
Published: June 2003

Automated theorem proving with connection tableau calculi imposes search problems in tremendous search spaces. In this paper, we present a new approach to search space reduction in connection tableau calculi. In our approach structurally similar parts of the search space are compressed by means of disjunctive constraints. We describe the necessary changes of the calculus, and we develop elaborate techniques for an efficient constraint processing. Moreover, we present an experimental evaluation of our approach.
A KNOWLEDGE-BASED ANSWER ENGINE FOR OPEN-DOMAIN QUESTIONS
Authors: HARABAGIU SANDA M. , PAŞCA MARIUS A. , MAIORANO STEVEN J.
Published: June 2003

This paper describes a knowledge-based methodology of mining textual answers from large collections of texts. We present an answer engine capable of providing answers to any question posed in natural language, regardless of the domain of interest. The answers are produced by combining semantic data from question taxonomies with information abductively inferred from texts. The high precision of the retrieved answers is due to novel, efficient knowledge processing techniques.
GENETIC ALGORITHMS FOR PARTITIONING SETS
Authors: GREENE WILLIAM A.
Published: June 2003

We first revisit a problem from the literature, that of partitioning a given set of numbers into subsets such that their sums are as nearly equal as possible. We devise a new genetic algorithm, Eager Breeder, for this problem. The algorithm is distinctive in its novel and aggressive way of extracting parental genetic material when forming a child partition, and its results are a substantial improvement upon prior results from the literature. Then we extend our algorithm to the more general setting, of partitioning a set in the case that the environment provides us a measure of the fitness of individual subsets in the partition. We apply the extension to two artificial problems, one with a targeted partition whose subsets are of very diverse sizes, and one whose subsets are the same size. Finally, we apply our approach to several map coloring problems, and obtain good results there as well. In our different stages of work, we exploit different heuristics, which are attuned to the particular partitioning problem under attack.
NEURAL NETWORK BASED CLASSIFICATION USING BLUR DEGRADATION AND AFFINE DEFORMATION INVARIANT FEATURES
Authors: ZHANG YANI , WEN CHANGYUN , ZHANG YING , SOH YENG CHAI
Published: June 2003

Identification of affine deformed and simultaneously blur degraded images is an important task in pattern analysis. In this paper, we introduce an image normalization approach to derive blur and affine combined moment invariants (BACIs). In our scheme, the lowest order blur invariant moments are used as the normalization constraints and an appropriate normalization procedure is designed to guarantee that the constraints used in each step should not be affected in the subsequent normalization steps. A neural network (NN) model is then employed to classify the degraded images using the proposed BACIs. Experimental results show that the system has high classification accuracy.
AN ALGEBRAIC APPROACH TO INDUCTIVE LEARNING
Authors: MARKOV ZDRAVKO
Published: June 2003

The paper presents a framework to induction of concept hierarchies based on consistent integration of metric and similarity-based approaches. The hierarchies used are subsumption lattices induced by the least general generalization operator (lgg) commonly used in inductive learning. Using some basic results from lattice theory the paper introduces a semantic distance measure between objects in concept hierarchies and discusses its applications for solving concept learning and conceptual clustering tasks. Experiments with well known ML datasets represented in three types of languages - propositional (attribute-value), atomic formulae and Horn clauses, are also presented.
EFFECTIVE AND EFFICIENT CACHING IN GENETIC ALGORITHMS
Authors: SANTOS EUNICE E. , SANTOS EUGENE
Published: June 2003

Hard discrete optimization problems using randomized methods such as genetic algorithms require large numbers of samples from the solution space. Each candidate sample/solution must be evaluated using the target fitness/energy function being optimized. Such fitness computations are a bottleneck in sampling methods such as genetic algorithms. We observe that the caching of partial results from these fitness computations can reduce this bottleneck. We provide a rigorous analysis of the run-times of GAs with and without caching. By representing fitness functions as classic Divide and Conquer algorithms, we provide a formal model to predict the efficiency of caching GAs vs. non-caching GAs. Finally, we explore the domain of protein folding with GAs and demonstrate that caching can significantly reduce expected run-times through both theoretical and extensive empirical analyses.
Remarks on nonlinear biharmonic evolution equation of Kirchhofftype in noncylindrical domain
Authors: Límaco J. , Clark H. R. , Medeiros L. A.
Published: June 2003

We investigate a boundary value problem for a nonlinear evolution
biharmonic operator motivated by flexion of fully clamped beam in two different physical situations. In the first, the supports of the ends of the beam are fixed and in the second one, the supports of the ends of the beam have small displacements.
Specific Phospholipid Oxidation Products Inhibit Ligand Activation of Toll-Like Receptors 4 and 2
Authors: Walton Kimberly A. , Cole Amy L. , Yeh Michael , Subbanagounder Ganesamoorthy , Krutzik Stephan R. , Modlin Robert L. , Lucas Robert M. , Nakai Junko , Smart Eric J. , Vora Deven K. , Berliner Judith A.
Published: June 2003

Objective—We have previously shown that phospholipid oxidation products of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (ox-PAPC) inhibit lipopolysaccharide (LPS)-induced E-selectin expression and neutrophil binding in human aortic endothelial cells (HAECs). The current studies identify specific phospholipids that inhibit chemokine induction by Toll-like receptor-4 (TLR4) and -2 (TLR2) ligands in

ECs and macrophages.

Methods and Results—Measurements of interleukin (IL)-8 and monocyte chemotactic protein-1 levels secreted from ox-PAPC- and LPS-cotreated ECs indicate that ox-PAPC inhibits activation of TLR4 by LPS. The effects of IL-1β and tumor necrosis factor-α, which utilize the same intracellular signaling molecules, were not inhibited. Cell fractionation and immunofluorescence analyses demonstrate that LPS induces membrane translocation of the LPS receptor complex to a lipid raft/caveolar fraction in ECs. Ox-PAPC inhibits this translocation and alters caveolin-1 distribution. Supporting an important role for caveolae in LPS action, overexpression of caveolin-1 enhanced LPS-induced IL-8 synthesis. Ox-PAPC also inhibits the effect of TLR2 and TLR4 ligands in human macrophages.

Conclusions—These studies report a novel mechanism that involves alterations to lipid raft/caveolar processing, by which specific phospholipid oxidation products inhibit activation by TLR4 and TLR2 ligands. These studies have broader implications for the role of ox-PAPC as a regulator of specific lipid raft/caveolar function.
Genetic Loci Contribute to the Progression of Vascular and Cardiac Hypertrophy in Salt-Sensitive Spontaneous Hypertension
Authors: Siegel Anja-Kristin , Planert Michael , Rademacher Sibylle , Mehr Ali Poyan , Kossmehl Peter , Wehland Markus , Stoll Monika , Kreutz Reinhold
Published: June 2003

Objective—

The salt-sensitive Dahl rat and the spontaneously hypertensive rat develop comparable spontaneous hypertension on a low-salt diet, whereas only the salt-sensitive Dahl rat strain develops a striking increase in blood pressure and cardiovascular hypertrophy on a high-salt diet. We set out to identify quantitative trait loci (QTLs) contributing to the progression of salt-induced organ damage in hypertension by studying an F
2
population derived from both strains.

Methods and Results—

We determined systolic blood pressure (SBP), vascular aortic hypertrophy (AH), cardiac left ventricular (LV) hypertrophy (LVH), and LV fibrosis in 230 male F
2
-animals on a high-salt diet. A strong correlation between AH and LVH was found (
r
=0.58,
P
<0.0001), and genome-wide QTL mapping detected suggestive or significant QTLs in overlapping chromosomal fragments for AH and LVH on chromosomes 1, 3, and 19, respectively. A significant influence of SBP on the extent of LVH and AH was evident at all QTLs, although significant linkage to SBP (together with LVH) was only found on chromosome 9. No QTLs for LV fibrosis were detected.

Conclusions—

This study demonstrates a strong correlation between AH and LVH in salt-sensitive hypertension and identifies QTLs contributing to the progression of cardiovascular hypertrophy in this condition.
Von Willebrand Factor But Not α-Thrombin Binding to Platelet Glycoprotein Ibα Is Influenced by the HPA-2 Polymorphism
Authors: Ulrichts Hans , Vanhoorelbeke Karen , Cauwenberghs Sandra , Vauterin Stephan , Kroll Hartmut , Santoso Sentot , Deckmyn Hans
Published: June 2003

Objective—

Glycoprotein (GP) Ibα is the functionally dominant subunit of the platelet GPIb-IX-V receptor complex. The N-terminal domain of the GPIbα chain contains binding sites for α-thrombin and von Willebrand factor (VWF). The human platelet alloantigen (HPA)-2 polymorphism of the GPIbα gene is associated with a C/T transition at nucleotide 1018, resulting in a Thr/Met dimorphism at residue 145 of GPIbα. To study the structural and functional effects of this dimorphism, N-terminal fragments (AA1-289) of the HPA-2a and HPA-2b alloform of GPIbα expressed in CHO cells were used.

Methods and Results—

Of 74 moAbs directed against human GPIbα, 2 antibodies with epitope between AA1-59 could differentiate between both alloforms. In addition, VWF bound with a higher affinity to the recombinant HPA-2a fragment or to homozygous HPA-2a platelets. In contrast, no difference was found in the binding of α-thrombin to the recombinant alloform fragments or of antibodies directed against the α-thrombin binding anionic sulfated tyrosine sequence (AA269-282).

Conclusions—

Whereas the Thr145Met dimorphism does not affect α-thrombin binding, it does influence the conformation of the N-terminal flanking region and first leucine-rich repeat of GPIbα and by this has an effect on VWF binding.
C-Reactive Protein, Interleukin-6, and Fibrinogen as Predictors of Coronary Heart Disease
Authors: Luc Gérald , Bard Jean-Marie , Juhan-Vague Irène , Ferrieres Jean , Evans Alun , Amouyel Philippe , Arveiler Dominique , Fruchart Jean-Charles , Ducimetiere Pierre
Published: June 2003

Objective—This study was undertaken to examine the association of plasma inflammatory markers such as C-reactive protein (CRP), interleukin-6, and fibrinogen with the incidence of coronary heart disease within the prospective cohort study on myocardial infarction (PRIME study).

Methods and Results—Multiple risk factors were recorded at baseline in 9758 men aged 50 to 59 years who were free of coronary heart disease (CHD) on entry. Nested case-control comparisons were carried out on 317 participants who suffered myocardial infarction (MI)-coronary death (n=163) or angina (n=158) as an initial CHD event during a follow-up for 5 years. After adjustment for traditional risk factors, incident MI-coronary death, but not angina, was significantly associated with CRP, interleukin-6, and fibrinogen, but only interleukin-6 remained significantly associated with MI-coronary death when the 3 inflammatory markers were included in the model. The different interleukin-6 levels in Northern Ireland and France partly explained the difference in risk between these countries. Interleukin-6 appeared as a risk marker of MI-coronary death, and it improved the definition of CHD risk beyond LDL cholesterol.

Conclusions—This association may reflect the underlying inflammatory reaction located in the atherosclerotic plaque or a genetic susceptibility on the part of CHD subjects to answer a proinflammatory stimulus and subsequent increase in hepatic CRP gene expression.
Restoration of Endothelial Function by Increasing High-Density Lipoprotein in Subjects With Isolated Low High-Density Lipoprotein
Authors: Bisoendial Radjesh J. , Hovingh G. Kees , Levels Johannes H.M. , Lerch Peter G. , Andresen Irmgard , Hayden Michael R. , Kastelein John J.P. , Stroes Erik S.G.
Published: June 2003

Background—

Loss-of-function mutations in the ATP-binding cassette (ABCA)-1 gene locus are the underlying cause for familial hypoalphalipoproteinemia, providing a human isolated low-HDL model. In these familial hypoalphalipoproteinemia subjects, we evaluated the impact of isolated low HDL on endothelial function and the vascular effects of an acute increase in HDL.

Methods and Results—

In 9 ABCA1 heterozygotes and 9 control subjects, vascular function was assessed by venous occlusion plethysmography. Forearm blood flow responses to the endothelium-dependent and -independent vasodilators serotonin (5HT) and sodium nitroprusside, respectively, and the inhibitor of nitric oxide synthase
N
G
-monomethyl-
l
-arginine (L-NMMA) were measured. Dose-response curves were repeated after systemic infusion of apolipoprotein A-I/phosphatidylcholine (apoA-I/PC) disks. At baseline, ABCA1 heterozygotes had decreased HDL levels (0.4±0.2 mmol/L;
P
<0.05), and their forearm blood flow responses to both 5HT (maximum, 49.0±10.4%) and L-NMMA (maximum, −22.8±22.9%) were blunted compared with control subjects (both
P
≤0.005). Infusion of apoA-I/PC disks increased plasma HDL to 1.3±0.4 mmol/L in ABCA1 heterozygotes, which resulted in complete restoration of vasomotor responses to both 5HT and L-NMMA (both
P
≤0.001). Endothelium-independent vasodilation remained unaltered throughout the protocol.

Conclusions—

In ABCA1 heterozygotes, isolated low HDL is associated with endothelial dysfunction, attested to by impaired basal and stimulated NO bioactivity. Strikingly, both parameters were completely restored after a single, rapid infusion of apoA-I/PC. These findings indicate that in addition to its long-term role within reverse cholesterol transport, HDL per se also exerts direct beneficial effects on the arterial wall.
B-Type Natriuretic Peptides and Ejection Fraction for Prognosis After Myocardial Infarction
Authors: Richards A. Mark , Nicholls M. Gary , Espiner Eric A. , Lainchbury John G. , Troughton Richard W. , Elliott John , Frampton Christopher , Turner John , Crozier Ian G. , Yandle Timothy G.
Published: June 2003

Background—

A recent landmark report has demonstrated that plasma B-type natriuretic peptide (BNP) measured in acute coronary syndromes independently predicts mortality, heart failure, and new myocardial infarction. After acute cardiac injury, left ventricular ejection fraction (LVEF) is also of prognostic significance and plays a major role in determining the therapeutic response.

Methods and Results—

The present report is the first from a substantial (n=666) cohort of patients with acute myocardial infarction to test the prognostic utility of concurrent measurements of BNP, amino-terminal BNP (N-BNP), norepinephrine, and radionuclide LVEF. The B-type peptides and LVEF were predictors of death, heart failure, and new myocardial infarction (all
P
<0.001) independent of patient age, gender, previous myocardial infarction, antecedent hypertension or diabetes, previous heart failure, plasma norepinephrine, creatinine, cholesterol, drug therapy, and coronary revascularization procedures. The combination of N-BNP (or BNP) with LVEF substantially improved risk stratification beyond that provided by either alone. Elevated N-BNP (or BNP) predicted new myocardial infarction only in patients with LVEF <40%. LVEF <40% coupled to N-BNP over the group median conferred substantial 3-year risks of death, heart failure, and new myocardial infarction of 37%, 18%, and 26%, respectively. N-BNP and BNP were equivalent prognostic markers for these clinical outcomes.

Conclusions—

Plasma N-BNP (or BNP) and LVEF are complementary independent predictors of major adverse events on follow-up after myocardial infarction. Combined measurement provides risk stratification substantially better than that provided by either alone.
Enhancement of Contractility With Sustained Afterload in the Intact Murine Heart
Authors: Reyes Maricela , Freeman Gregory L. , Escobedo Daniel , Lee Shuko , Steinhelper Mark E. , Feldman Marc D.
Published: June 2003

Background—

It has been hypothesized that because of its rapid heart rate, the intact murine heart functions near maximal contractility in the basal state. If this hypothesis is correct, then the fast and slow components of myocardial length-dependent activation should be blunted compared with larger mammals.

Methods and Results—

Mice (n=24) were anesthetized, and via an open chest, LV pressure-volume relationships were determined by a dual-frequency conductance catheter system. Baseline pressure-volume relationships were determined during transient occlusion of the inferior vena cava, and repeat measurements were made after 1 (n=10) and 7 (n=21) minutes of sustained aortic occlusion. Control experiments were performed in a subset of mice (n=3). For baseline to 1 minute, an increase in afterload (maximal pressure 95±9 to 126±7 mm Hg;
P
<0.001) and effective arterial elastance (5.9±3.1 to 9.2±3.9 mm Hg/μl;
P
<0.001) resulted in an increase in end-diastolic volume (31±8 to 35±9 μL;
P
<0.001). The result was maintenance of stroke volume (17±6 to 15±6;
P
=NS) owing to an increase in contractility (leftward shift in V
100
[the volume of end-systolic elastance at 100 mm Hg], 24±9 to 16±5 μL;
P
<0.001). No additional augmentation of systolic function was found at 7 minutes.

Conclusions—

This study demonstrates that the fast phase of length-dependent activation is intact but not the slow phase, consistent with murine myocardium functioning near maximal contractility in the basal state.
Coronary Endothelial Dysfunction Is Associated With an Increased Risk of Cerebrovascular Events
Authors: Targonski Paul V. , Bonetti Piero O. , Pumper Geralyn M. , Higano Stuart T. , Holmes David R. , Lerman Amir
Published: June 2003

Background—

Stroke, mainly attributable to atherothrombotic disease, represents a leading cause of disability and death in the Western world. Endothelial dysfunction, which is considered a key factor in atherogenesis, is associated with an increased risk of cardiovascular events. However, the magnitude of the association between coronary endothelial dysfunction (CED) and cerebrovascular events is unknown. This study was performed to investigate the association between CED and cerebrovascular events.

Methods and Results—

We studied 503 patients without obstructive coronary artery disease (CAD) who underwent coronary endothelial function testing by intracoronary acetylcholine infusion. Patients were divided according to the presence (n=305) or absence (n=198) of CED, and medical records were examined for the occurrence of ischemic or hemorrhagic stroke or transient ischemic attack either before (prevalent) or after (incident) coronary endothelial function testing. Among the study population, a total of 25 cerebrovascular events were documented, 22 in patients with CED (15 prevalent) and 3 in patients without (all prevalent) (
P
=0.008). Multivariable logistic regression, which included traditional cerebrovascular disease–related risk factors, identified the presence of CED as the single strongest factor associated with cerebrovascular events (OR, 4.32; 95% CI, 1.26 to 14.83). Kaplan-Meier analysis indicated that patients with CED had a significantly higher cumulative cerebrovascular event rate than those without (
P
=0.04).

Conclusions—

Presence of CED in patients without obstructive CAD is independently associated with an increased risk of cerebrovascular events. Thus, detection of this early stage of atherosclerosis may provide important information to identify patients who benefit from aggressive preventive strategies.
Interferon-β Treatment Eliminates Cardiotropic Viruses and Improves Left Ventricular Function in Patients With Myocardial Persistence of Viral Genomes and Left Ventricular Dysfunction
Authors: Kühl Uwe , Pauschinger Matthias , Schwimmbeck Peter Lothar , Seeberg Bettina , Lober Conny , Noutsias Michel , Poller Wolfgang , Schultheiss Heinz-Peter
Published: June 2003

Background—

Viral infections are important causes of myocarditis and may induce cardiac dysfunction and finally lead to dilated cardiomyopathy. We investigated whether interferon (IFN)-β therapy is safe and may achieve virus clearance and prevent deterioration of left ventricular (LV) function in patients with myocardial virus persistence.

Methods and Results—

In this phase II study, 22 consecutive patients with persistence of LV dysfunction (history of symptoms, 44±27 months) and polymerase chain reaction–proven enteroviral or adenoviral genomes were treated with 18×10
6
IU/week IFN-β (Beneferon) subcutaneously for 24 weeks. Histological and immunohistological analysis of endomyocardial biopsies was used to characterize myocardial inflammation. LV diameters and ejection fraction were assessed by echocardiography and angiography, respectively. During the treatment period, IFN-β was well tolerated by all patients. No patient deteriorated. Clearance of viral genomes was observed in 22 of 22 of patients after antiviral therapy. Virus clearance was paralleled by a significant decrease of LV end diastolic and end systolic diameters, decreasing from 59.7±11.1 to 56.5±10.0 mm (
P
<0.001) and 43.2±13.6 to 39.4±12.1 mm (
P
<0.001), respectively. LV ejection fraction increased from 44.6±15.5% to 53.1±16.8% (
P
<0.001).

Conclusions—

A 6 months, IFN-β treatment was safe in patients with myocardial enteroviral or adenoviral persistence and LV dysfunction and resulted in elimination of viral genomes (22 of 22 patients) and improved LV function (15 of 22 patients).
Temporal Relations of Atrial Fibrillation and Congestive Heart Failure and Their Joint Influence on Mortality
Authors: Wang Thomas J. , Larson Martin G. , Levy Daniel , Vasan Ramachandran S. , Leip Eric P. , Wolf Philip A. , D’Agostino Ralph B. , Murabito Joanne M. , Kannel William B. , Benjamin Emelia J.
Published: June 2003

Background—

Atrial fibrillation (AF) and congestive heart failure (CHF) frequently occur together, but there is limited information regarding their temporal relations and the combined influence of these conditions on mortality.

Methods and Results—

We studied participants in the Framingham Study with new-onset AF or CHF. Multivariable Cox proportional hazards models with time-dependent variables were used to evaluate whether mortality after AF or CHF was affected by the occurrence and timing of the other condition. Hazard ratios (HRs) were adjusted for time period and cardiovascular risk factors. During the study period, 1470 participants developed AF, CHF, or both. Among 382 individuals with both conditions, 38% had AF first, 41% had CHF first, and 21% had both diagnosed on the same day. The incidence of CHF among AF subjects was 33 per 1000 person-years, and the incidence of AF among CHF subjects was 54 per 1000 person-years. In AF subjects, the subsequent development of CHF was associated with increased mortality (men: HR 2.7; 95% CI, 1.9 to 3.7; women: HR 3.1; 95% CI, 2.2 to 4.2). Similarly, in CHF subjects, later development of AF was associated with increased mortality (men: HR 1.6; 95% CI, 1.2 to 2.1; women: HR 2.7, 95% CI, 2.0 to 3.6). Preexisting CHF adversely affected survival in individuals with AF, but preexisting AF was not associated with adverse survival in those with CHF.

Conclusions—

Individuals with AF or CHF who subsequently develop the other condition have a poor prognosis. Additional studies addressing the pathogenesis, prevention, and optimal management of the joint occurrence of AF and CHF appear warranted.
Intravascular Ultrasound Analysis of Infarct-Related and Non–Infarct-Related Arteries in Patients Who Presented With an Acute Myocardial Infarction
Authors: Kotani Jun-ichi , Mintz Gary S. , Castagna Marco T. , Pinnow Ellen , Berzingi Chalak O. , Bui Anh B. , Pichard Augusto D. , Satler Lowell F. , Suddath William O. , Waksman Ron , Laird John R. , Kent Kenneth M. , Weissman Neil J.
Published: June 2003

Background—

Previous studies have reported diffuse destabilization of atherosclerotic plaques in acute myocardial infarction (AMI).

Methods and Results—

We used intravascular ultrasound (IVUS) to assess 78 coronary arteries (38 infarct-related arteries [IRAs] with culprit and nonculprit lesions and 40 non-IRAs) from 38 consecutive AMI patients. IVUS analysis included qualitative and quantitative measurements of reference and lesion external elastic membrane (EEM), lumen, and plaque plus media (P&M) area. Positive remodeling was defined as lesion/mean reference EEM >1.0. Culprit lesions were identified by a combination of ECG, wall motion abnormalities (ventriculogram or echocardiogram), scintigraphic perfusion defects, and coronary angiogram. Culprit lesions contained more thrombus (23.7% versus 3.4% in nonculprit IRA plaques and 3.1% in non-IRA plaques;
P
=0.0011). Culprit lesions were predominantly hypoechoic (63.2% versus 37.9% of nonculprit IRA plaques and 28.1% of non-IRA plaques;
P
=0.0022). Culprit lesions were longer (17.5±10.1, 9.8±4.0, and 10.3±5.7 mm, respectively;
P
<0.0001), had larger EEM area (15.0±6.0, 11.5±5.7, and 12.6±5.6 mm
2
, respectively;
P
=0.0353) and P&M area (13.0±6.0, 7.5±3.7, 9.3±4.3 mm
2
, respectively;
P
<0.0001), smaller lumens (2.0±0.9, 4.1±3.1, and 3.4±2.5 mm
2
, respectively;
P
=0.0009), and more positive remodeling (79.4%, 59.0%, and 50.8%, respectively;
P
=0.0155). The frequency of plaque rupture/dissection was greater in culprit, nonculprit IRA, and non-IRA plaques in AMI patients than in a control group of chronic stable angina patients with multivessel IVUS imaging.

Conclusions—

Culprit plaques have more markers of instability (thrombus, positive remodeling, and large plaque mass); however, these markers of instability are not typically found elsewhere. This suggests that the vascular event in AMI patients is determined by local pre-event lesion morphologies.
Adverse Effect of Ventricular Pacing on Heart Failure and Atrial Fibrillation Among Patients With Normal Baseline QRS Duration in a Clinical Trial of Pacemaker Therapy for Sinus Node Dysfunction
Authors: Sweeney Michael O. , Hellkamp Anne S. , Ellenbogen Kenneth A. , Greenspon Arnold J. , Freedman Roger A. , Lee Kerry L. , Lamas Gervasio A.
Published: June 2003

Background—

Dual-chamber (DDDR) pacing preserves AV synchrony and may reduce heart failure (HF) and atrial fibrillation (AF) compared with ventricular (VVIR) pacing in sinus node dysfunction (SND). However, DDDR pacing often results in prolonged QRS durations (QRSd) as the result of right ventricular stimulation, and ventricular desynchronization may result. The effect of pacing-induced ventricular desynchronization in patients with normal baseline QRSd is unknown.

Methods and Results—

Baseline QRSd was obtained from 12-lead ECGs before pacemaker implantation in MOST, a 2010-patient, 6-year, randomized trial of DDDR versus VVIR pacing in SND. Cumulative percent ventricular paced (Cum%VP) was determined from stored pacemaker data. Baseline QRSd <120 ms was observed in 1339 patients (707 DDDR, 632 VVIR). Cum%VP was greater in DDDR versus VVIR (90% versus 58%,
P
=0.001). Cox models demonstrated that the time-dependent covariate Cum%VP was a strong predictor of HF hospitalization in DDDR (hazard ratio [HR], 2.99 [95% CI, 1.15 to 7.75] for Cum%VP >40%) and VVIR (HR 2.56 [95% CI, 1.48 to 4.43] for Cum%VP >80%). The risk of AF increased linearly with Cum%VP from 0% to 85% in both groups (DDDR, HR 1.36 [95% CI, 1.09, 1.69]; VVIR, HR 1.21 [95% CI 1.02, 1.43], for each 25% increase in Cum%VP). Model results were unaffected by adjustment for known baseline predictors of HF hospitalization and AF.

Conclusions—

Ventricular desynchronization imposed by ventricular pacing even when AV synchrony is preserved increases the risk of HF hospitalization and AF in SND with normal baseline QRSd.
Neutrophil Elastase in Human Atherosclerotic Plaques
Authors: Dollery Clare M. , Owen Caroline A. , Sukhova Galina K. , Krettek Alexandra , Shapiro Steven D. , Libby Peter
Published: June 2003

Background—

Catabolism of the extracellular matrix (ECM) contributes to vascular remodeling in health and disease. Although metalloenzymes and cysteinyl proteinases have garnered much attention in this regard, the role of serine-dependent proteinases in vascular ECM degradation during atherogenesis remains unknown. We recently discovered the presence of the metalloproteinase MMP-8, traditionally associated only with neutrophils, in atheroma-related cells. Human neutrophil elastase (NE) plays a critical role in lung disease, but the paucity of neutrophils in the atheromatous plaque has led to neglect of its potential role in vascular biology. NE can digest elastin, fibrillar and nonfibrillar collagens, and other ECM components in addition to its ability to modify lipoproteins and modulate cytokine and MMP activity.

Methods and Results—

Fibrous and atheromatous plaques but not normal arteries contained NE. In particular, NE abounded in the macrophage-rich shoulders of atheromatous plaques with histological features of vulnerability. Neutrophil elastase and macrophages colocalized in such vulnerable plaques (n=7). In situ hybridization revealed NE mRNA in macrophage-rich areas, indicating local production of this enzyme. Freshly isolated blood monocytes, monocyte-derived macrophages, and vascular endothelial cells in culture produced active NE and contained NE mRNA. Monocytes produced NE constitutively, with little regulation by cytokines IL-1β, TNF-α, or IFN-γ but released it when stimulated by CD40 ligand, a cytokine found in atheroma.

Conclusions—

These findings point to a novel role for the serine protease, neutrophil elastase, in matrix breakdown by macrophages, a critical process in adaptive remodeling of vessels and in the pathogenesis of arterial diseases.