bluuebunny/crossref_metadata_2025 huggingface dataset:
Relatives’ knowledge of decision making in intensive care: Table 1
Authors: Booth M G , Doherty P , Fairgrieve R , Kinsella J
Published: October 2004

Background/Aim:The law on consent has changed in Scotland with the introduction of the Adults with Incapacity (Scotland) Act 2000. This Act introduces the concept of proxy consent in Scotland. Many patients in intensive care are unable to participate in the decision making process because of their illness and its treatment. It is normal practice to provide relatives with information on the patient’s condition, treatment, and prognosis as a substitute for discussion directly with the patient. The relatives of intensive care patients appeared to believe that they already had the right to consent on behalf of an incapacitated adult. The authors’ aim was to assess the level of knowledge among relatives of intensive care patients of both the old and new law using a structured questionnaire.

Methods:The next of kin of 100 consecutive patients completed a structured questionnaire. Each participant had the questions read to them and their answers recorded. Patients were not involved in the study.

Results:Few (10%) were aware of the changes. Most (88%) thought that they previously could give consent on behalf of an incapacitated adult. Only 13% have ever discussed the preferences for life sustaining treatment with the patient but 84% felt that they could accurately represent the patient’s wishes.

Conclusions:There appeared to be a lack of public awareness of the impending changes. The effectiveness of the Act at improving the care of the mentally incapacitated adult will depend largely on how successful it is at encouraging communication and decision making in advance of incapacity occurring.
There is a difference between selecting a deaf embryo and deafening a hearing child
Authors: Häyry M
Published: October 2004

If genetic diagnosis and preimplantation selection could be employed to produce deaf children, would it be acceptable for deaf parents to do so? Some say no, because there is no moral difference between selecting a deaf embryo and deafening a hearing child, and because it would be wrong to deafen infants. It is argued in this paper, however, that this view is untenable. There are differences between the two activities, and it is perfectly possible to condone genetic selection for deafness while condemning attempts to deafen infants at birth.
Pressure and coercion in the care for the addicted: ethical perspectives
Authors: Janssens M J P A , Van Rooij M F A M , ten Have H A M J , Kortmann F A M , Van Wijmen F C B
Published: October 2004

The use of coercive measures in the care for the addicted has changed over the past 20 years. Laws that have adopted the “dangerousness” criterion in order to secure patients’ rights to non-intervention are increasingly subjected to critique as many authors plead for wider dangerousness criteria. One of the most salient moral issues at stake is whether addicts who are at risk of causing danger to themselves should be involuntarily admitted and/or treated. In this article, it is argued that the dilemma between coercion on the one hand and abandonment on the other cannot be analysed without differentiated perspectives on the key notions that are used in these debates. The ambiguity these notions carry within care practice indicates that the conflict between the prevention of danger and respect for autonomy is not as sharp as the legal systems seem to imply. Some coercive measures need not be interpreted as an infringement of autonomy—rather, they should be interpreted as a way to provide good care.
Troponin T: how high is high? Relationship and differences between serum cardiac markers according to level of creatine kinase and type of myocardial infarction
Authors: Williams S G , Silas J H , Joseph F , Jackson M , Rittoo D , Currie P
Published: October 2004

Cardiac troponins have emerged over recent years as the “gold standard” serum biochemical marker for the diagnosis and management for patients with acute myocardial infarction (MI). The relationship between old (creatine kinase; CK) and new (troponin T; TT) markers of myocardial injury were examined in this study of 392 consecutive patients admitted to a district hospital with a diagnosis of an acute MI. Significant correlation of serum TT and peak CK levels were seen (R = 0.58, p<0.0001) in all types of MI. A significant relationship was also seen according to type of MI (Q wave or non-Q wave MI) or peak CK level. The regression equation (TT (μg/l) = 0.0027 (peak CK) + 1.1160 (IU/l)) may be used by clinicians to estimate TT release from a known peak CK result and thus provide some guidance on equivalence between the two tests. Our findings provide physicians with a benchmark reference range between the two cardiac markers, according to level of peak CK.
The 12, 24, or is it 26 cranial nerves?
Authors: Welsby P D
Published: October 2004

Many of our perceptions are gained through interpretative organs that we assume to be providing objective accounts. Notably, however, neither vision nor hearing provide an objective account of reality. This paper challenges the “conventional wisdoms” held regarding the optic, auditory, and hypoglossal nerves, and the nerves of eye movement.
Therapeutic impact of percutaneous spinal biopsy in spinal infection
Authors: Rankine J J , Barron D A , Robinson P , Millner P A , Dickson R A
Published: October 2004

Objective: To investigate the therapeutic impact of percutaneous spinal biopsy in patients with suspected spinal infection.

Design and patients: A review of the case notes and imaging features of 36 patients who underwent percutaneous spinal biopsy was performed. From this group 20 patients with a prebiopsy diagnosis of spinal osteomyelitis were identified. Management before biopsy was noted including the use of antimicrobial therapy. The results of the histology and microbiology were noted along with the subsequent diagnosis and management.

Results: Eight of the 20 patients (40%) had received antibiotics before the biopsy. An organism was isolated in 8/20 cases (40%). Of the eight patients on antibiotics, two grew an organism (25%), including one case of candida in a patient receiving flucloxacillin. Out of 12 patients not on antibiotics there were six cases where an organism was isolated (50%). The result of the biopsy led to a change in management in seven of the 20 patients (35%).

Conclusions: Many clinicians are treating spinal osteomyelitis empirically with antibiotics before biopsy, but this reduces the chance of isolating an organism and determining antibiotic sensitivity. Despite this biopsy led to a change in management in 35% of cases.
Dengue viral infections
Authors: Malavige G N , Fernando S , Fernando D J , Seneviratne S L
Published: October 2004

Dengue viral infections are one of the most important mosquito borne diseases in the world. They may be asymptomatic or may give rise to undifferentiated fever, dengue fever, dengue haemorrhagic fever (DHF), or dengue shock syndrome. Annually, 100 million cases of dengue fever and half a million cases of DHF occur worldwide. Ninety percent of DHF subjects are children less than 15 years of age. At present, dengue is endemic in 112 countries in the world. No vaccine is available for preventing this disease. Early recognition and prompt initiation of appropriate treatment are vital if disease related morbidity and mortality are to be limited. This review outlines aspects of the epidemiology of dengue infections, the dengue virus and its mosquito vector, clinical features and pathogenesis of dengue infections, and the management and control of these infections.
Infective endocarditis from Enterococcus faecalis complicating colonoscopy in Heyde’s syndrome
Authors: Giusti de Marle M , Sgreccia A , Carmenini E , Morelli S
Published: October 2004

A case of infective endocarditis from Enterococcus faecalis after colonoscopy in a patient with aortic stenoinsufficiency and bleeding intestinal angiodysplasia (Heyde’s syndrome) is reported.

A 77 year old man with aortic stenoinsufficiency presented with enterorrhagia and underwent a colonoscopy, which showed normal findings. Fifteen days later he developed a moderate degree of fever. Blood cultures were positive for E faecalis. An echocardiogram showed aortic valve vegetations, and infective endocarditis was diagnosed and successfully treated by antibiotics. Some months later, intestinal bleeding recurred and intestinal resection was performed. Histopathology showed angiodysplasia.

In patients with Heyde’s syndrome antibiotic prophylaxis should be considered before colonoscopy.
Denitrification in the Upper Mississippi River: rates, controls, and contribution to nitrate flux
Authors: Richardson William B , Strauss Eric A , Bartsch Lynn A , Monroe Emy M , Cavanaugh Jennifer C , Vingum Lorrine , Soballe David M
Published: October 2004

We evaluated patterns of denitrification and factors effecting denitrification in the upper Mississippi River. Measurements were taken over 2 years, during which river discharge ranged from record flooding to base flow conditions. Over the period of study, average denitrification enzyme activity was highest in backwater lakes and lowest in the main channel. Throughout the study reach, highest denitrification enzyme activity occurred during fall and lowest occurred in winter. Rates during spring floods (2001) were only slightly higher than during the preceding winter. Mean unamended denitrification rates ranged from 0.02 (fall 2001 in backwaters) to 0.40 µg N·cm2·h1(spring 2001 in backwaters). Laboratory experiments showed that denitrification rates increased significantly with addition of NO3regardless of sediment C content, while rates increased little with addition of labile C (glucose). Denitrification in this reach of the upper Mississippi River appears to be NO3limited throughout the growing season and the delivery of NO3is strongly controlled by river discharge and hydrologic connectivity across the floodplain. We estimate that denitrification removes 6939 t N·year1or 6.9% of the total annual NO3input to the reach. Hydrologic connectivity and resultant NO3delivery to high-C sediments is a critical determinant of reach-scale processing of N in this floodplain system.
Inferring age from otolith measurements: a review and a new approach
Authors: Francis RIC Chris , Campana Steven E
Published: October 2004

In 1985, Boehlert (Fish. Bull. 83: 103117) suggested that fish age could be estimated from otolith measurements. Since that time, a number of inferential techniques have been proposed and tested in a range of species. A review of these techniques shows that all are subject to at least one of four types of bias. In addition, they all focus on assigning ages to individual fish, whereas the estimation of population parameters (particularly proportions at age) is usually the goal. We propose a new flexible method of inference based on mixture analysis, which avoids these biases and makes better use of the data. We argue that the most appropriate technique for evaluating the performance of these methods is a costbenefit analysis that compares the cost of the estimated ages with that of the traditional annulus count method. A simulation experiment is used to illustrate both the new method and the costbenefit analysis.
THE LONG RUN OUTCOMES AND GLOBAL DYNAMICS OF A DUOPOLY GAME WITH MISSPECIFIED DEMAND FUNCTIONS
Authors: BISCHI GIAN-ITALO , CHIARELLA CARL , KOPEL MICHAEL
Published: October 2004

In this paper we study a model of a quantity-setting duopoly market where firms lack knowledge of the market demand. Using a misspecified demand function firms determine their profit-maximizing choices of their corresponding perceived market game. For illustrative purposes we assume that the (true) demand function is linear and that the reaction functions of the players are quadratic. We then investigate the global dynamics of this game and characterize the number of steady states and their welfare properties. We study the basins of attraction of these steady states and present situations in which global bifurcations of their basins occur when model parameters are varied. The economic significance of our result is to show that in situations where players choose their actions based on a misspecified model of the environment, additional self-confirming steady states may emerge, despite the fact that the Nash-equilibrium of the game under perfect knowledge is unique. As a consequence the long run outcome of the game and overall welfare is highly dependent upon initial conditions.
A HUMANOID INTERACTION ROBOT FOR INFORMATION, NEGOTIATION AND ENTERTAINMENT USE
Authors: HACKEL MATTHIAS , SCHWOPE STEFAN
Published: October 2004

This paper presents the design, implementation and application of a humanoid interaction robot (H10). In interdisciplinary cooperation H10 was developed as a case study to operate at points of sale, information desks and demonstrations. If the user given speech input matches an entry of the adaptive database, H10 will react with a suitable answer. Synchronously to the speech generation, face animation and pre-defined gestures of hands and arms are triggered by the core of the system. The principles of the speech, gesture and physical interaction interface as well as some fundamental mechanic and electronic details are described.
REAL-TIME SELF-COLLISION AVOIDANCE SYSTEM FOR ROBOTS USING ROBE
Authors: SETO FUMI , KOSUGE KAZUHIRO , HIRATA YASUHISA
Published: October 2004

In this paper, we propose a real-time self-collision avoidance system for robots which cooperate with a human/humans. First, the robot is represented by elastic elements. The representation method is referred to as RoBE (Representation of Body by Elastic elements). Elastic balls and cylinders are used as the elements to simplify collision detection, although elements of any shape could be used for RoBE. When two elements collide with each other, a reaction force is generated between them, and self-collision avoidance motion is generated by the reaction force. Experiments using the mobile robot with dual manipulators, referred to as MR Helper, illustrate the validity of the proposed system.
SENSORS, IDENTIFICATION, AND LOW LEVEL CONTROL OF A FLEXIBLE ANTHROPOMORPHIC ROBOT HAND
Authors: MARTIN JAN , BECK SEBASTIAN , LEHMANN ARNE , MIKUT RALF , PYLATIUK CHRISTIAN , SCHULZ STEFAN , BRETTHAUER GEORG
Published: October 2004

The successful control of a robot hand with multiple degrees of freedom not only requires sensors to determine the state of the hand but also a thorough understanding of the actuator system and its properties. This article presents a set of sensors and analyzes the actuator properties of an anthropomorphic robot hand driven by flexible fluidic actuators. These flexible and compact actuators are integrated directly into the finger joints, they can be driven either pneumatically or hydraulically.

The sensors for the measurement of joint angles, contact forces, and fluid pressure are described; the designs utilize mostly commodity components. Hall sensors and customized half-ring rare-earth magnets are used to integrate the joint angle sensors directly into the actuated joints. A force sensor setup allowing soft finger surfaces is evaluated. Fluid pressure sensors are needed for the model-based computation of joint torques and to limit the actuator pressure.

Static and dynamic actuator characteristics are determined in a theoretical process analysis, and suitable parameters are identified in several experiments. The resulting actuator model incorporates the viscoelastic material behavior and describes the relations of joint angle, actuator pressure, and actuator torque. It is used in simulations and for the design of a joint position controller.
HUMANOID ROBOT APPLICATIONS IN HRP
Authors: YOKOI KAZUHITO , KAWAUCHI NAOTO , SAWASAKI NAOYUKI , NAKAJIMA TOSHIYA , NAKAMURA SHINYA , SAWADA KAZUYA , TAKEUCHI IKUO , NAKASHIMA KATSUMI , YANAGIHARA YOSHITAKA , YOKOYAMA KAZUHIKO , ISOZUMI TAKAKATSU , FUKASE YUTARO , KANEKO KENJI , INOUE HIROCHIKA
Published: October 2004

The Ministry of Economy, Trade and Industry (METI) of Japan ran an R&D project on humanoid robotics, called HRP. In the project, a humanoid robotics platform was developed in the first phase, and contributors of the project followed up with research on the applications of humanoid robots to various industries. In this paper, we describe the five applications that we think are suitable for humanoid robots and expect to open a new industry.
THE STORY OF PINO
Authors: KITANO HIROAKI , YAMASAKI FUMINORI , MATSUI TATSUYA , ENDO KEN , MATSUOKA YUKIKO , KAMINAGA HIROSHI , KATO YUICHIRO
Published: October 2004

PINO is a small-sized, low-cost humanoid robot developed for research. The salient feature of PINO is the use of low-cost components, extensive esthetic design, the disclosure of technical information under GNU General Public Licensing, the use of evolutionarly computing methods to generate stable walking patterns, and numerious commerical developments. In fact, PINO is the first biped humanoid robot that was sold as a commercial product. Currently, PINO-II is on the market with various improved aspects of PINO. This article describe ideas behind PINO, and how it was developed and transferred into the industrial sector.
WHO IS AFRAID OF THE HUMANOID? INVESTIGATING CULTURAL DIFFERENCES IN THE ACCEPTANCE OF ROBOTS
Authors: KAPLAN FRÉDÉRIC
Published: October 2004

Are robots perceived in the same manner in the West and in Japan? This article presents a preliminary exploration of several aspects of the Japanese culture and a survey of the most important myths and novels involving artificial beings in Western literature. Through this analysis, the article tries to shed light on particular cultural features that may account for contemporary differences in our behavior towards humanoids.
Effects of endogenous estrogen on renal calcium and phosphate handling in elderly women
Authors: Dick I. M. , Devine A. , Beilby J. , Prince R. L.
Published: October 2004

High postmenopausal endogenous estrogen concentrations are an important determinant of preservation of bone mass and reduced fracture in elderly women. Calcium supplementation can also reduce bone loss in these patients, suggesting an interaction between estrogen deficiency and calcium balance. Potential mechanisms of estrogen on calcium transport include direct effects on the bone, the kidney, and the bowel. Previous studies have demonstrated effects of estrogen on renal phosphate handling. We have used a cross-sectional, population-based analysis of biochemical data obtained from ambulant elderly women to determine the association of endogenous estradiol with urine calcium and phosphorus excretion. The subjects were 293 postmenopausal women >70 yr old. Factors associated with renal calcium and phosphate excretion were measured, including the filtered calcium and phosphate load, parathyroid hormone (PTH), estradiol, and sex hormone-binding globulin (SHBG). The free estradiol concentration (FE) was calculated from a previously described formula. A high plasma estradiol concentration ( r2 = 0.023, P = 0.01) and a high FE ( r2 = 0.045, P = 0.001) were associated with reduced renal calcium excretion. The estradiol and FE effect on renal calcium excretion remained significant after adjusting for calcium filtered at the glomerulus and serum PTH. A high FE was associated with a reduced renal phosphate threshold in univariate analysis ( r2 = 0.023, P = 0.010). The effect remained significant after adjustment for serum PTH. The size of the effect of the FE was of the same order of magnitude as the effect of PTH on reducing renal calcium excretion and increasing renal phosphate excretion. These data support in vitro and animal data demonstrating an effect of estradiol on renal calcium and phosphate handling and indicate that, in elderly postmenopausal women, the effect is of a similar magnitude to the well-recognized effects of PTH on these physiologically regulated parameters.
Polymorphonuclear leukocyte and monocyte activation induced by plasma from patients with heparin-induced thrombocytopenia in whole blood
Authors: Khairy Mahnouch , Lasne Dominique , Amelot Aymeric , Crespin Malvina , Rendu Francine , Aiach Martine , Bachelot-Loza Christilla
Published: October 2004

Heparin-induced thrombocytopenia (HIT), a severe complication of heparin therapy, results from platelet activation by heparin-dependent antibodies. Previously, we have shown that plasma from patients with HIT (HIT plasma) induces leukocyteplatelet aggregation in blood. In this report, we examined leukocyte activation by HIT plasma and the contribution of heparin and platelets to this activation, in whole blood. Degranulation of leukocytes from HIT patients was evaluated as a leukocyte activation marker. We showed that polymorphonuclear leukocytes (PMN) and monocytes were the leukocyte subpopulations involved in platelet-leukocyte aggregation induced by HIT plasma in healthy donor blood. PMN and monocyte activation, reflected by increased surface expression of the CD11b adhesion molecule, was induced by HIT plasma in a heparin-dependent manner. The CD11b increase induced by HIT plasma was observed on PMN only when they were associated with platelets. Moreover, the increased CD11b expression on monocytes and PMN correlated strongly with the degree of platelet adhesion to these cells. Degranulation of leukocytes from HIT patients and control subjects (non-HIT heparin-treated patients and healthy subjects) was evaluated in vivo by measuring the plasma myeloperoxidase concentration. HIT plasma contained higher myeloperoxidase concentrations than control plasma, suggesting leukocyte degranulation during HIT. In conclusion, this study provides the first evidence that PMN activation is induced by HIT plasma. HIT plasma induced PMN and monocyte activation in a heparin-dependent manner. In whole blood, platelet association with monocytes and PMN, and the activation of these leukocytes by HIT plasma were interrelated. Finally, leukocyte degranulation could be involved in HIT physiopathology.
Comparison of two methods to assess variability of platelet response to anti-platelet therapies in patients with acute coronary syndrome undergoing angioplasty
Authors: Boughrassa Faiza , Chapman-Montgomery E. , Poisson Véronique , Gervais André , Okrongly David , Grant Andrew , Ahnadi Charaf
Published: October 2004

The study investigated the clinical usefulness of a new method to evaluate platelet activation and the variability of platelet response to anti-platelet therapy in patients undergoing percutaneous transluminal coronary angioplasty (PTCA). Platelet activation was assessed in parallel by a new method for platelet density measurements (MPC, Mean Platelet Component Concentration), on the automated ADVIA 120 Hematology System and by the classic measurement of P-selectin (CD62P) expression, on a fluorescence flow cytometer. Patients received a loading dose of clopidogrel (300 mg; n = 29) or a bolus of abciximab (0.25 mg/kg; n = 15). Blood samples were collected before (baseline) and at different times after PTCA and antiplatelet drugs administration. Our data showed a close inverse correlation between the change in MPC and the CD62P fluorescence surface marker expression (r = 0.776, P<0.0001). Individual platelet activation determinations in patients receiving either clopidogrel or abciximab showed a variation in platelet activation as assayed by MPC and CD62P expression. Patients were characterized as having either high platelet activity upon admission and positive response to treatment or no detectable platelet activation before or after treatment. This study demonstrates the heterogeneity of platelet activation states in ACS patients undergoing coronary angioplasty. The present work also illustrates the potential use of the MPC parameter, generated on an automated hematology system, to define high risk patients and to monitor the variability of platelet response to anti-platelet therapies.
Effect of Interleukin-6 promoter polymorphisms in survivors of myocardial infarction and matched controls in the North and South of Europe
Authors: Kelberman Daniel , Hawe E. , Luong L. A. , Mohamed-Ali Vidya , Lundman Pia , Tornvall Per , Aillaud M. F. , Juhan-Vague Irène , Yudkin John , Margaglione Maurizio , di Minno Giovanni , Tremoli Elena , Humphries Stephen ,   on behalf of the HIFMECH study group
Published: October 2004

Elevated plasma IL-6 levels have been implicated in the pathogenesis of coronary heart disease. We have investigated the association of two polymorphisms in the promoter of IL-6 (-572G>C and -174G>C) with levels of inflammatory markers and risk of myocardial infarction (MI) in a European study of MI survivors and age-matched controls from two high-risk centres in the North of Europe, and two low risk centres in the South. IL-6 and CRP levels were similar in controls in both regions, but were higher in cases. For the -174G>C polymorphism the rare -174C allele showed a regional difference in allele frequency, being more common in the North European group (0.43 vs 0.28; p < 0.0005), where -174C allele carriers showed an apparent reduced risk of MI compared to -174GG homozygotes (OR 0.53, 95%CI 0.32, 0.86). No such effect was observed in the South or with the -572G>C in either group. Neither genotype was associated with a significant effect on plasma IL-6 levels in either cases or controls. Furthermore, no regional difference was observed in the frequency of the -572G>C SNP, suggesting that these polymorphisms are unlikely to be contributing to the observed increased risk of cardiovascular disease in Northern Europe.
Herpes simplex virus type 1-encoded glycoprotein C enhances coagulation factor VIIa activity on the virus
Authors: Sutherland Michael , Friedman Harvey , Pryzdial Edward
Published: October 2004

Tissue factor (TF) is the blood coagulation initiator, whose cofactor function is required for physiological factor VIIa (FVIIa)-mediated activation of factor X (FX) to FXa. A previous study reported TF on herpes simplex virus type 1 (HSV1), but this explained only part of FVIIa-dependent FXa generation observed on the virus surface (Sutherland et al. (1997) Proc. Natl. Acad. Sci. USA. 94:13510-14). In the current study, we investigated the role of HSV1-encoded glycoprotein C (gC) in this process. Purified gC-deficient HSV1 facilitated several fold less FX activation by FVIIa than either wild type or gC-rescued strains.To confirm the implication of gC in FVIIa-dependent FX activation, purified soluble gC (sgC) enhanced FXa production in the absence of TF. sgC required FVIIa, calcium and anionic phospholipid to participate in FX activation, suggesting similarity to TF. When purified virus was combined with sgC, the sgC-dependent FXa generation was enhanced three orders of magnitude, suggesting synergy with an additional HSV1 component and explaining the relatively low activity of purified sgC compared to the viral counterpart. FX activation on gC-competent HSV1 was inhibited 20% by a gC-specific antibody, inhibited 40% by a TF-specific antibody, inhibited 65% by combining the gCand TF-specific antibodies, and nearly completely inhibited by the TF antibody alone on gC-deficient HSV-1. Cumulatively, these observations show that two pathways initiating FX activation function in parallel on the virus surface. In addition to the previously described TF-dependent pathway, HSV-1-encoded gC also enhances FXa generation, and like TF, requires FVIIa.
The story of the serpin plasminogen activator inhibitor 1: is there any need for another mutant?
Authors: De Taeye Bart , Gils Ann , Declerck Paul
Published: October 2004

The importance of obtaining insight in the structure/function relationship in the serpin plasminogen activator inhibitor type1 can be understood from the major role PAI-1 plays in different (patho)physiological processes, mainly because of its involvement in the plasminogen/plasmin system. Moreover, during the past years, studies indicated a contribution of PAI-1 to the development of cardiovascular disease in common syndromes such as atherosclerosis, diabetes and hypertension. Furthermore, PAI-1 also inhibits u-PA, attributing a role in phenomena such as cell migration and tissue remodelling. Considering the role of PAI-1 in such various pathogenic pathways, detailed insight into the structure/function relationship in PAI-1 might provide a means of interfering with a given pathological situation without disturbing other physiological processes. Therefore, since the discovery of PAI-1 and the cloning of its cDNA 20 years ago, over 600 PAI-1 variants have been constructed, elucidating the most important structural features of PAI-1. This review gives an overview of the contribution of the different PAI-1 variants to the understanding of the structure/function relationship in PAI-1, based on the different functional features of PAI-1.
Elevated D-dimer level is an independent risk factor for cardiovascular death in out-patients with symptoms compatible with heart failure
Authors: Dahlström Ulf , Lindahl Tomas , Alehagen Urban
Published: October 2004

D-dimer, a marker of fibrin turnover, exhibits many interesting properties as a biological marker of thrombosis. Some of the properties of D-dimer might also be used to provide additional information about patients with heart failure. In this study, we evaluate the prognostic information acquired from D-dimer concerning increased risk of cardiovascular mortality in an elderly population with symptoms associated with heart failure. A cardiologist examined 458 elderly patients, out of 548 invited, attending primary care for symptoms of dyspnoea, fatigue and/or peripheral oedema and assessed NYHA functional class and cardiac function. Abnormal systolic function was defined as EF <40% on Doppler echocardiography. Abnormal diastolic function was defined as reduced E/A ratio and/or an abnormal pattern of pulmonary venous flow. Blood samples were drawn, and BNP and D-dimer were analysed. D-dimer was analysed using an automated micro-latex assay. A statistical analysis was performed to identify the prognostic value of increased plasma concentration of D-dimer. Results showed that during a median follow-up period of 5.5 years, 68 (14%) patients died of cardiovascular disease. No gender difference was noted. A plasma concentration of D-dimer >0.25mg/L increased the risk almost 4-fold. In conclusion, D-dimer is an independent risk factor for cardiovascular mortality that may be used to risk-stratify patients with heart failure.
Plasma fibrinogen concentration predicts the risk of myocardial infarction differently in various parts of Europe: effects of β-fibrinogen genotype and environmental factors
Authors: Silveira Angela , Hawe Emma , Eriksson Per , Aillaud Marie , Juhan-Vague Irene , Yudkin John , Margaglione Maurizio , di Minno Giovanni , Mussoni Luciana , Tremoli Elena , Humphries Steve , Hamsten Anders , Mannila Maria ,   the HIFMECH study group
Published: October 2004

The propensity to atherothrombotic disease differs in Europe, with high-risk regions located in the North of Europe and lowrisk regions in the South of Europe. The HIFMECH study (Hypercoagulability and Impaired Fibrinolytic function MECHanisms predisposing to myocardial infarction (MI) study) was undertaken to elucidate genetic and environmental mechanisms underlying MI based on investigations of postinfarction patients and healthy individuals recruited from Stockholm, Sweden, London, England (North of Europe), Marseille, France and San Giovanni Rotondo, Italy (South of Europe). In the present report, emphasis was placed on fibrinogen, a multifunctional protein, widely recognized as an independent predictor of atherothrombotic disease. The adjusted plasma fibrinogen concentration was an independent discriminator between cases and controls in London (SOR 3.58; 95% CI 1.31; 9.83), but not in the other centres. Genotyping for six β-fibrinogen promoter single nucleotide polymorphisms was performed of which -249C/T, -455G/A and -854G/A were used in analysis as a consequence of the linkage disequilibrium pattern. Four haplotypes, with similar distribution across Europe, were detected: CGG (46.7%), CAG (20.3%), TGG (18.2%) and CGA (14.8%). A significant haplotype effect on plasma fibrinogen concentration was observed in patients (p <0.001) but not in controls (p = 0.08).The -455G/A genotype related to plasma fibrinogen concentration amongst patients along with centre and IL-6 concentration (together explaining 11.5% of the variation), whereas predictors amongst controls included centre, body mass index, IL-6 and smoking habit (explaining 15.7%). Thus, plasma fibrinogen concentration contributes differently to MI across Europe, and a disease-related stimulus is required to evoke allele-specific regulation of fibrinogen synthesis.
Accelerating ability of synthetic oligosaccharides on antithrombin inhibition of proteinases of the clotting and fibrinolytic systems Comparison with heparin and low-molecular-weight heparin
Authors: Olson Steven , Swanson Richard , Raub-Segall Elke , Bedsted Tina , Sadri Morvardi , Petitou Maurice , Hérault Jean-Pascal , Herbert Jean-Marc , Björk Ingemar
Published: October 2004

The abilities of three synthetic oligosaccharides to accelerate antithrombin inhibition of ten clotting or fibrinolytic proteinases were compared with those of unfractionated, fractionated high-affinity and low-molecular-weight heparins. The results show that the anticoagulant effects of the latter three heparins under conditions approximating physiologic are exerted almost exclusively by acceleration of the inactivation of thrombin, factor Xa and factor IXa to near diffusion-controlled rate constants of ∼106 – 107 M−1·s−1. All other proteinases are inhibited with at least 20-fold lower rate constants. The anticoagulant ability of the synthetic regular (fondaparinux) and high-affinity (idraparinux) pentasaccharides is due to a common mechanism, involving acceleration of only factor Xa inhibition to rate constants of ∼106 M−1·s−1. A synthetic hexadecasaccharide, containing both the pentasaccharide sequence and a proteinase binding site, exerts its anticoagulant effect by accelerating antithrombin inactivation of both thrombin and factor Xa to rate constants of ∼106 – 107 M−1·s−1, although thrombin appears to be the more important target. In contrast, factor IXa inhibition is appreciably less stimulated. The conformational change of antithrombin induced both by the pentasaccharides and longer heparins contributes substantially, ∼150–500-fold, to accelerating the inactivation of factors Xa, IXa and VIIa and moderately, ∼50-fold, to that of factor XIIa and tissue plasminogen activator inhibition. The bridging effect due to binding of antithrombin and proteinase to the same, long heparin chain is dominating, ∼1000–3000-fold, for thrombin inhibition and is appreciably smaller, although up to ∼250-350-fold, for the inactivation of factors IXa and XIa. These results establish the proteinase targets of heparin derivatives currently used in or considered for thrombosis therapy and give new insights into the mechanism of heparin acceleration of antithrombin inhibition of proteinases.
Thrombin activatable fibrinolysis inhibitor and its fibrinolytic effect in normal pregnancy
Authors: Mousa Hatem , Downey Colin , Alfirevic Zarko , Toh Cheng-Hock
Published: October 2004

We investigated changes in both thrombin activatable fibrinolysis inhibitor (TAFI) antigen levels and its functional effect on in vitro fibrinolysis in normal pregnancy. 152 pregnant women and 31 women in the immediate postpartum period were studied, with pregnancy divided into 6 windows at 4 weekly intervals. As TAFI influences and is in turn influenced by components of the protein C (PC) pathway, its measurements were correlated with levels of soluble thrombomodulin, PC, protein S (PS) and the overall phenotype of activated PC resistance (APCR). Compared with mean TAFI levels at booking gestation (6.6 +1.2 μg/ml), levels peaked at 35-39 weeks gestation (9.6 +2 μg/ml, p = 0.001), followed by a significant drop within 24 hours of delivery (7.2 + 1.1 μg/ml). In functional terms, the mean clot lysis time (CLT) (101 + 13 min at booking) also peaked at 35-39 weeks gestation (141 + 42 min, p = 0.007) and dropped after delivery (99 + 33 min), and was significantly correlated with gestational age (r = 0.410, p = 0.001) and could be abrogated in the presence of an inhibitor to TAFI activation. A significant negative correlation was found between TAFI levels and APCR (r = −0.478, p <0.001), APCRV (r = −0.598; p <0.001), PS (r = −0.490, P <0.001) and PC (r = −0.198, p = 0.02). In summary, there is a significant increase in TAFI levels, which translates into increased CLT during pregnancy. Furthermore, changes in TAFI contribute to the increasing APCR of pregnancy.
Ambient Pollution and Blood Pressure in Cardiac Rehabilitation Patients
Authors: Zanobetti Antonella , Canner Marina Jacobson , Stone Peter H. , Schwartz Joel , Sher David , Eagan-Bengston Elizabeth , Gates Karen A. , Hartley L. Howard , Suh Helen , Gold Diane R.
Published: October 2004

Background—

Multiple studies have demonstrated a consistent association between ambient particulate air pollution and increased risk of hospital admissions and deaths for cardiovascular causes. We investigated the associations between fine particulate pollution (PM
2.5
) and blood pressure during 631 repeated visits for cardiac rehabilitation in 62 Boston residents with cardiovascular disease.

Methods and Results—

Blood pressure, cardiac risk factor, and exercise data were abstracted from records of rehabilitation visits between 1999 and 2001. We applied mixed-effect models, controlling for body mass index, age, gender, number of visits, hour of day, and weather variables. For an increase from the 10th to the 90th percentile in mean PM
2.5
level during the 5 days before the visit (10.5 μg/m
3
), there was a 2.8-mm Hg (95% CI, 0.1 to 5.5) increase in resting systolic, a 2.7-mm Hg (95% CI, 1.2 to 4.3) increase in resting diastolic, and a 2.7-mm Hg (95% CI, 1.0 to 4.5) increase in resting mean arterial blood pressure. The mean PM
2.5
level during the 2 preceding days (13.9 μg/m
3
) was associated with a 7.0-mm Hg (95% CI, 2.3 to 12.1) increase in diastolic and a 4.7-mm Hg (95% CI, 0.5 to 9.1) increase in mean arterial blood pressure during exercise in persons with resting heart rate ≥70 bpm, but it was not associated with an increase in blood pressure during exercise in persons with heart rate <70 bpm.

Conclusions—

In patients with preexisting cardiac disease, particle pollution may contribute to increased risk of cardiac morbidity and mortality through short-term increases in systemic arterial vascular narrowing, as manifested by increased peripheral blood pressure.
Atherosclerosis in Patients Infected With HIV Is Influenced by a Mutant Monocyte Chemoattractant Protein-1 Allele
Authors: Alonso-Villaverde Carlos , Coll Blai , Parra Sandra , Montero Manuel , Calvo Nahum , Tous Mònica , Joven Jorge , Masana Lluis
Published: October 2004

Background—

Patients infected with HIV present with premature atherosclerosis, and the 2 diseases share common pathogenic pathways. We investigated mutations in the monocyte chemoattractant protein-1 (MCP-1) and CCR-2 genes, which are known to control aspects of these pathways, to ascertain whether they are involved in atherogenesis in these patients.

Methods and Results—

We performed carotid and femoral artery ultrasonography to detect subclinical atherosclerosis in patients infected with HIV (n=183). MCP-1–2518G and CCR-2 64I polymorphisms were determined in the HIV group and in a population-based control group (n=348). We also determined MCP-1 circulating levels in the HIV group. The presence of MCP-1–2518G in the group of patients with subclinical atherosclerosis was significantly higher than in patients without atherosclerotic lesions (47.5% versus 18.2%, respectively;
P
<0.001). Furthermore, the patients with atherosclerotic lesions had higher MCP-1 plasma concentrations than did patients without lesions (74.15 [4.03] versus 57.81 [3.67] pg/mL, respectively;
P
=0.03). When adjusted for known cardiovascular risk factors, the MCP-1–2518G allele was associated with subclinical atherosclerosis (OR 5.72, 95% CI 1.74 to 18.80,
P
=0.004). Compared with measurements conducted ≈2.5 years earlier in a subset of 40 patients, intima-media thickness (IMT) in the carotid artery progressed at a mean rate of 0.06 mm/y more rapidly in patients bearing the MCP-1-mutated allele (
P
=0.08).

Conclusions—

HIV-infected patients with the MCP-1–2518G allele have a 5-fold increased risk for atherosclerosis, as assessed by ultrasonography.
Signaling Molecules in Overcirculation-Induced Pulmonary Hypertension in Piglets
Authors: Rondelet Benoit , Kerbaul François , Van Beneden Ronald , Motte Sophie , Fesler Pierre , Hubloue Ives , Remmelink Myriam , Brimioulle Serge , Salmon Isabelle , Ketelslegers Jean-Marie , Naeije Robert
Published: October 2004

Background—

The phosphodiesterase type-5 (PDE-5) inhibitor sildenafil has been reported to improve pulmonary arterial hypertension (PAH), but the mechanisms that account for this effect are incompletely understood. Severe pulmonary hypertension has been characterized by defects in a signaling pathway involving angiopoietin-1 and the bone morphogenetic receptor-2 (BMPR-2). We investigated the effects of sildenafil on hemodynamics and signaling molecules in a piglet overcirculation-induced model of early PAH.

Methods and Results—

Thirty 3-week-old piglets were randomized to placebo or sildenafil therapy 0.75 mg/kg TID after anastomosis of the left subclavian artery to the pulmonary arterial trunk or after a sham operation. Three months later, the animals underwent a hemodynamic evaluation followed by pulmonary tissue sampling for morphometry, immunohistochemistry or radioimmunoassay, and real-time quantitative-polymerase chain reaction. Chronic systemic-to-pulmonary shunting increased pulmonary mRNA for angiopoietin-1, endothelin-1 (ET-1), angiotensin II, inducible nitric oxide synthase, vascular endothelial growth factor, and PDE-5. Pulmonary messenger RNA for BMPR-1A and BMPR-2 decreased. Pulmonary angiotensin II, ET-1, and vascular endothelial growth factor proteins increased. Pulmonary artery pressure increased from 20±2 to 33±1 mm Hg, and arteriolar medial thickness increased by 91%. The expressions of angiopoietin-1, ET-1, and angiotensin II were tightly correlated to pulmonary hypertension. Sildenafil prevented the increase in pulmonary artery pressure, limited the increase in medial thickness to 41%, and corrected associated biological perturbations except for the angiopoietin-1/BMPR-2 pathway, PDE-5, and angiotensin II.

Conclusions—

Sildenafil partially prevents overcirculation-induced PAH and associated changes in signaling molecules. Angiotensin II, PDE-5, and angiopoietin-1/BMPR-2 signaling may play a dominant role in the early stages of the disease.
Allopurinol Attenuates Left Ventricular Remodeling and Dysfunction After Experimental Myocardial Infarction
Authors: Engberding Niels , Spiekermann Stephan , Schaefer Arnd , Heineke André , Wiencke Antje , Müller Maja , Fuchs Martin , Hilfiker-Kleiner Denise , Hornig Burkhard , Drexler Helmut , Landmesser Ulf
Published: October 2004

Background—

Accumulating evidence suggests a critical role for increased reactive oxygen species (ROS) production in left ventricular (LV) remodeling and dysfunction after myocardial infarction (MI). Increased expression of xanthine oxidase (XO), a major source of ROS, has recently been demonstrated in experimental and clinical heart failure; however, a potential role for LV remodeling processes remains unclear. We therefore studied the effect of long-term treatment with allopurinol, a potent XO inhibitor, on myocardial ROS production and LV remodeling and dysfunction after MI.

Methods and Results—

Mice with extensive anterior MI (n=105) were randomized to treatment with either vehicle or allopurinol (20 mg · kg
−1
· d
−1
by gavage) for 4 weeks starting on day 1 after surgery. Infarct size was similar among the groups. XO expression and activity were markedly increased in the remote myocardium of mice after MI, as determined by electron spin resonance spectroscopy. Myocardial ROS production was increased after MI but markedly reduced after allopurinol treatment. Importantly, allopurinol treatment substantially attenuated LV cavity dilatation and dysfunction after MI, as assessed by echocardiography, and markedly reduced myocardial hypertrophy and interstitial fibrosis.

Conclusion—

The present study reveals a novel beneficial effect of treatment with allopurinol, ie, a marked attenuation of LV remodeling processes and dysfunction after experimental MI. Allopurinol treatment therefore represents a potential novel strategy to prevent LV remodeling and dysfunction after MI.
Histological Correlates of Carotid Plaque Surface Morphology on Lumen Contrast Imaging
Authors: Lovett J.K. , Gallagher P.J. , Hands L.J. , Walton J. , Rothwell P.M.
Published: October 2004

Background—

Carotid angiographic plaque surface morphology is a powerful risk factor for stroke and systemic vascular risk. However, the underlying pathology is unclear, and a better understanding is required both to evaluate other forms of carotid imaging and to develop new treatments. Previous studies comparing angiographic plaque surface morphology with pathology have been small and unblinded, and the vast majority assessed only the crude macroscopic appearance of the plaque. We performed the first large study comparing angiographic surface morphology with detailed histology.

Methods and Results—

Carotid plaque surface morphology was classified as ulcerated, irregular, or smooth on 128 conventional selective carotid artery angiograms from consecutive patients undergoing endarterectomy for severe symptomatic stenosis. Blinded angiographic assessments were compared with 10 histological features recorded on detailed microscopy of the plaque using reproducible semiquantitative scales. Angiographic ulceration was associated with plaque rupture (
P
=0.001), intraplaque hemorrhage (
P
=0.001), large lipid core (
P
=0.005), less fibrous tissue (
P
=0.003), and increased instability overall (
P
=0.001). For example, angiographically ulcerated plaques were much more likely than smooth plaques to be ruptured (OR=15.4, 95% CI=2.7 to 87.3,
P
<0.001), show a large lipid core (OR=26.7, 95% CI=2.6 to 270,
P
<0.001) or a large hemorrhage (OR=17.0, 95% CI=2.0 to 147,
P
=0.02). The equivalent odds ratios for angiographically irregular versus smooth plaque were 6.3 (1.3 to 31,
P
=0.02), 6.7 (1.5 to 30,
P
=0.008), and 9.2 (1.1 to 77,
P
=0.02), respectively.

Conclusions—

In contrast to previous studies based on macroscopic assessment, we found very strong associations between detailed histology and carotid angiographic plaque surface morphology. Plaque surface morphology on carotid angiography is a highly sensitive marker of plaque instability. Studies of the predictive value of MR- and CT-based lumen contrast plaque surface imaging are required.