bluuebunny/crossref_metadata_2025 huggingface dataset:
Cell-based therapy facilitates venous thrombus resolution
Authors: Ballmoos Moritz Wyler von , Diehm Nicolas , Völzmann Jan , Baumgartner Iris , Santo Stefano Di , Tepper Oren M. , Kalka Christoph
Published: February 2009

Endothelial progenitor cells (EPC) are involved in many healing processes in cardiovascular diseases and can be found in spontaneously resolving venous thrombi. The purpose of the present study was to investigate whether the therapeutic administration of EPC might enhance the resolution of venous thrombi. For this purpose, venous thrombosis was induced in the infrarenal inferior vena cava (IVC) in 28 athymic nude rats. Culture expanded EPC derived from human peripheral blood mononuclear cells were injected intravenously two and four days after thrombus induction. Recanalisation of the IVC and thrombus organisation were assessed by laser Doppler measurements of the blood flow and immunohistochemical detection of endothelialised luminal structures in the thrombus. EPC transplantation resulted in significantly enhanced thrombus neovascularisation (capillary density: 186.6 ± 26.7/HPF vs. 78 ± 12.3/HPF, p<0.01; area covered by capillaries: 8.9 ± 1.7 µm2 vs. 2.5 ± 1.3 µm2, p<0.01) and was accompanied by a substantial increase in intrathrombus blood flow (perfusion ratio: 0.7 ± 0.07 vs. 0.3 ± 0.08, p<0.02). These results were paralleled by augmented macrophage recruitment into resolving thrombi in the animals treated with EPC (39.4 ± 4.7/HPF vs. 11.6 ± 1.9/HPF, p<0.01). Our data suggest that EPC transplantation might be of clinical value to facilitate venous thrombus resolution in cases where current therapeutic options have limited success.
Rapid molecular diagnosis of von Willebrand disease by direct sequencing. Detection of 12 novel putative mutations in VWF gene
Authors: Corrales Irene , Ramírez Lorena , Altisent Carme , Parra Rafael , Vidal Francisco
Published: February 2009

Molecular diagnosis of von Willebrand Disease (VWD) is particularly complex. The autosomal von Willebrand factor gene (VWF) is large and highly polymorphic, and there is a highly homologous (>96%) partial pseudogene in chromosome 22. Because of these difficulties, application of molecular study of VWD to the clinical routine has been considerably delayed. Recent advances in sequencing technology and bioinformatics could convert direct sequencing of the complete VWF into a routine diagnostic tool for VWD, which is especially desirable in types 1 and 3. This study describes a highly optimized procedure in which all the coding and intronic flanking regions of VWF are amplified under identical thermocycling parameters in a ready-to-use PCR plate format. The entire sequencing procedure, from blood extraction to mutation identification, can be done within 24 hours, resulting in a simple, versatile, cost-effective strategy with little hands-on time requirements. To validate the method, we performed full-length VWF sequencing of 21 index cases including seven of each VWD type. A total of 30 VWF genetic variations were identified. Twelve of these sequence variations are new, including four missense, one nonsense, one insertion, the first insertion-deletion described in VWF, and 5 potential splice site mutations. To our knowledge, this is the fastest and most efficient protocol designed to date for complete sequencing of the VWF coding region in the molecular diagnosis of VWD.
Levels of inflammatory markers and the development of the post-thrombotic syndrome
Authors: Shbaklo Hadia , Holcroft Christina A. , Kahn Susan R.
Published: February 2009

The post-thrombotic syndrome (PTS) occurs frequently after deep venous thrombosis (DVT) despite appropriate anticoagulant therapy. A close relationship between inflammation and thrombosis exists. While the inflammatory process at the time of DVT appears to improve thrombus resolution, it may promote destruction of venous valves, valvular reflux and subsequent development of PTS. We prospectively evaluated the association between levels of four cytokines (IL-6, IL-8, IL-10 and MCP-1), two adhesion molecules (ICAM-1 and VCAM-1) and the development of PTS in a well-defined cohort of patients with DVT. The study population consisted of 387 patients with objectively diagnosed symptomatic DVT who were followed for two years to determine the incidence of PTS. At the end of follow-up, plasma samples frozen at the four-month visit in 307 study patients were thawed and analyzed for the above inflammatory markers using the Luminex beads technology. Mean levels of IL-6 were significantly higher in patients with PTS compared to patients without PTS (7.35 pg/ml ± 14.26 [SD] vs. 4.60 pg/ml ± 4.90;p=0.03). Logistic regression analyses showed significant associations between PTS and levels above vs. below the median of IL-6 [odds ratio (OR) 1.66; 95% confidence interval (CI) 1.05, 2.62 (p=0.03)] and ICAM-1 [OR 1.63; 95% CI 1.03, 2.58 (p=0.04)]. None of the other markers showed any association with PTS. Our study suggests the presence of significant associations between markers of inflammation such as IL-6 and ICAM-1 and the development of PTS. Further work is needed to evaluate this relationship and to analyse other candidate markers that could be implicated etiologically in the association between DVT and PTS. If confirmed, this could lead to identification of new therapeutic targets for preventing PTS after DVT.
Cell-derived microparticles in haemostasis and vascular medicine
Authors: Burnier Laurent , Fontana Pierre , Kwak Brenda R. , Angelillo-Scherrer Anne
Published: February 2009

Considerable interest for cell-derived microparticles has emerged, pointing out their essential role in haemostatic response and their potential as disease markers, but also their implication in a wide range of physiological and pathological processes. They derive from different cell types including platelets – the main source of microparticles – but also from red blood cells, leukocytes and endothelial cells, and they circulate in blood. Despite difficulties encountered in analyzing them and disparities of results obtained with a wide range of methods, microparticle generation processes are now better understood. However, a generally admitted definition of microparticles is currently lacking. For all these reasons we decided to review the literature regarding microparticles in their widest definition, including ectosomes and exosomes, and to focus mainly on their role in haemostasis and vascular medicine.
Venous thromboembolism in pregnancy: diagnosis, management and prevention
Authors: Bates Shannon M. , Chunilal Sanjeev D.
Published: February 2009

A pregnant woman has a two- to five-fold higher risk of venous thromboembolism (VTE) than a non-pregnant woman of the same age and, in developed countries, she is more likely to die from fatal pulmonary embolism (PE) than from obstetric haemorrhage. The increased VTE risk is mediated through normal physiological changes of pregnancy including alterations in haemostasis that favour coagulation, reduced fibrinolysis and pooling and stasis of blood in the lower limbs. Thrombophilia, smoking, obesity, immobility and postpartum factors such as infection, bleeding and emergency surgery (including emergency caesarian section) also increase the risk of pregnancy-related VTE. The diagnosis of VTE can be safely established with acceptable radiation exposure to the fetus using readily available imaging modalities such as ultrasound, ventilation perfusion lung scanning and computed tomographic pulmonary angiography. However, the optimal diagnostic strategies still remain to be determined. If there is no contraindication to anticoagulation, commencing treatment prior to objective confirmation should be strongly considered. For the mother and fetus, effective and safe treatment is readily available with low-molecular-weight heparin (LMWH), but optimal dosing of these agents in pregnancy remains controversial. Emerging data support antepartum LMWH prophylaxis for women with previous VTE if the event was unprovoked or in the presence of thrombophilia. On the other hand, women with prior provoked VTE and no thrombophilia or women with asymptomatic thrombophilia (but a family history of VTE) can safely be managed with antepartum surveillance. Postpartum prophylaxis is recommended for women with prior VTE or thrombophilia (and a family history of VTE).
International normalised ratio (INR) measured on the CoaguChek S and XS compared with the laboratory for determination of precision and accuracy
Authors: Larsen Torben B. , Jensen Claus , Maegaard Marianne , Sørensen Benny , Christensen Thomas D.
Published: February 2009

Oral anticoagulation therapy is monitored by the use of international normalised ratio (INR). Patients performing self-management estimate INR using a coagulometer, but studies have been partly flawed regarding the estimated precision and accuracy. The objective was to estimate the imprecision and accuracy for two different coagulometers (CoaguChek® S and XS). Twenty-four patients treated with coumarin were prospectively followed for six weeks. INR’s were analyzed weekly in duplicates on both coagulometers, and compared with results from the hospital laboratory. Statistical analysis included Bland-Altman plot, 95% limits of agreement, coefficient of variance (CV), and an analysis of variance using a mixed effect model. Comparing 141 duplicate measurements (a total of 564 measurements) of INR, we found that the CoaguChek S and CoaguChek XS had a precision (CV) of 3.4% and 2.3%, respectively. Regarding analytical accuracy, the INR measurements tended to be lower on the coagulometers, and regarding diagnostic accuracy the CoaguChek S and CoaguChek XS deviated more than 15% from the laboratory measurements in 40% and 43% of the measurements, respectively. In conclusion, the precision of the coagulometers was found to be good, but only the CoaguChek XS had a precision within the predefined limit of 3%. Regarding analytical accuracy, the INR measurements tended to be lower on the coagulometers, compared to the laboratory. A large proportion of measurement of the coagulometers deviated more than 15% from the laboratory measurements. Whether this will have a clinical impact awaits further studies.
Subtherapeutic oral anticoagulant therapy: Frequency and risk factors
Authors: Rombouts Eva K. , Rosendaal Frits R. , van der Meer Felix J. M.
Published: February 2009

Subtherapeutic anticoagulation levels increase both the risk and severity of thromboembolism. The aim of this study was to determine the cumulative incidence of subtherapeutic international normalised ratios (INRs) and to identify risk factors associated with a low INR. We performed a cohort study in 7,419 patients from a Dutch anticoagulation clinic. Patients who started a first treatment with oral anticoagulants between January 2000 and December 2005 and who were stably anticoagulated (4 consecutive INRs in the therapeutic range) were included. Within the cohort a nested case control study was performed to identify risk factors of subtherapeutic INRs and to determine how often a subtherapeutic INR is the result of medical interference in case of invasive procedures, hospital admissions, haemorrhage or overanticoagulation. In patients with a stable anticoagulation, the median time to a first low INR was 40 weeks. A subtherapeutic INR occurred twice as often in patients using acenocoumarol as in those using phenprocoumon (hazard ratio [HR] 2.1, 95% confidence interval [95%CI]:2.0 – 2.3) and was more common in patients with a high therapeutic range compared to a low therapeutic range (HR 1.8, 95%CI:1.5 – 2.2). Occurrence of a low INR also depended on indication for anticoagulant therapy, with the highest risk in patients who used anticoagulants as prophylaxis and the lowest risk in patients with mechanical heart valves. In 30% of cases the subtherapeutic INR was preceded by an event necessitating vitamin K or discontinuation of the anticoagulant drug.
Plasma free tissue factor pathway inhibitor (TFPI) levels and TF-induced thrombin generation ex vivo in men with low testosterone levels
Authors: Agledahl Ingvild , Svartberg Johan , Hansen Bjarne , Brodin Ellen
Published: February 2009

Low testosterone levels in men have been associated with cardiovascular risk factors, some prothrombotic factors, and lately also an increased risk of both cardiovascular disease and all-cause mortality. Experimental studies have shown increased synthesis and release of tissue factor pathway inhibitor (TFPI) by physiological levels of testosterone in endothelial cells. Our hypothesis was that elderly men with low testosterone levels would have lower plasma levels of plasma free TFPI with subsequent increased thrombin generation. Elderly men with low (n=37) and normal (n=41) testosterone levels were recruited from a general population, and tissue factor (TF)-induced thrombin generation ex vivo and plasma free TFPI Ag were measured. Elderly men with low testosterone levels had lower plasma free TFPI Ag (10.9 ± 2.3 ng/ml vs. 12.3 ± 3.0 ng/ml, p=0.027) and shorter initiation phase of TF-induced coagulation assessed by lag-time (5.1 ± 1.0 min vs. 5.7 ± 1.3, p=0.039). The differences between groups remained significant and were strengthened after adjustment for waist circumference and other cardiovascular risk factors. Lag-time increased linearly across quartiles of plasma free TFPI Ag (p<0.001). Multiple regression analysis revealed that total and free testosterone were independent predictors of plasma free TFPI Ag. Our findings suggest that low testosterone levels in elderly men is associated with low plasma free TFPI Ag and subsequent shortened initiation phase of TF-induced coagulation.
Endothelial Function Predicts Progression of Carotid Intima-Media Thickness
Authors: Halcox Julian P.J. , Donald Ann E. , Ellins Elizabeth , Witte Daniel R. , Shipley Martin J. , Brunner Eric J. , Marmot Michael G. , Deanfield John E.
Published: February 2009

Background—

Endothelial dysfunction develops early and has been shown to predict the development of clinical complications of atherosclerosis. However, the relationship between early endothelial dysfunction and the progression of arterial disease in the general population is unknown. We investigated endothelial dysfunction, risk factors, and progression of carotid intima-media thickness (cIMT) in late-middle-aged individuals at low to intermediate cardiovascular risk in a prospective study between 1997 and 2005.

Methods and Results—

Brachial artery flow-mediated dilatation and cIMT were measured in 213 nonsmoking British civil servants recruited from a prospective cohort (Whitehall II study). Participants (age, 45 to 66 years) were free of clinical cardiovascular disease and diabetes mellitus. Risk factors and Framingham Risk Score were determined at baseline. cIMT was repeated 6.2±0.4 years later. At baseline, age, blood pressure, low-density lipoprotein cholesterol, and Framingham Risk Score correlated with cIMT. However, only flow-mediated dilatation, not risk factors or Framingham Risk Score, was associated with average annual progression of cIMT. This relationship remained significant after adjustment for risk factors whether entered as separate variables or as Framingham Risk Score. Further adjustment for waist circumference, triglycerides, and employment grade had no significant effect.

Conclusions—

Systemic endothelial function was associated with progression of preclinical carotid arterial disease over a 6-year period and was more closely related to cIMT changes than conventional risk factors. Thus, the relationship between endothelial dysfunction and adverse outcome is likely to be due not only to destabilization of established disease in high-risk populations but also to its impact on the evolution of the atherosclerotic substrate. Flow-mediated dilatation testing provides an integrated vascular measure that may aid the prediction of structural disease evolution and represents a potential short- to intermediate-term outcome measure for evaluation of preventive treatment strategies.
Temporal Changes in Coronary Revascularization Procedures, Outcomes, and Costs in the Bare-Metal Stent and Drug-Eluting Stent Eras
Authors: Ryan Jason , Linde-Zwirble Walter , Engelhart Luella , Cooper Liesl , Cohen David J.
Published: February 2009

Background—

Although drug-eluting stents have been shown to be cost-effective compared with bare-metal stents for select clinical trial patients, whether these findings apply to the general population is unknown.

Methods and Results—

We used data from the Medicare 5% Standard Analytic Files to compare the practice and outcomes of coronary revascularization (by either percutaneous coronary intervention or coronary artery bypass grafting) in the United States between 2001 (pre–drug-eluting stent era, n=14 362) and 2004 (post–drug-eluting stent era, n=16 374). Between 2001 and 2004, the rate of revascularization increased from 837 to 931 per 100 000, whereas the proportion of patients who underwent percutaneous coronary intervention as an initial revascularization procedure increased from 67.5% to 75.2% (
P
<0.001). Over a median follow-up period of 25.5 months, no significant changes in mortality were found between 2001 and 2004 (13.8% versus 13.3%,
P
=0.193). Significant decreases were seen, however, in the incidence of repeat revascularization (17.1% versus 16.0%,
P
=0.012) and myocardial infarction (10.6% versus 8.5%,
P
<0.001). Over this same time period, total cardiovascular care costs per revascularized patient decreased by $1680 (95% confidence interval $1164 to $2196,
P
<0.001) whereas total noncardiovascular costs increased by $2481 per patient (95% confidence interval $1844 to $3118,
P
<0.001). When the impact of overall procedural volumes was considered, aggregate cost to the Medicare program for cardiovascular services increased by $544 million over the 2-year follow-up period. Risk-adjusted results for both the clinical and economic outcomes showed similar trends.

Conclusions—

Among the Medicare population undergoing coronary revascularization, the introduction of drug-eluting stents was associated with increased use of initial percutaneous coronary intervention and reduced bypass surgery along with improved clinical outcomes over ≈2 years of follow-up. Although total cardiovascular-related costs per revascularized patient decreased over this time period, total cost to the Medicare system still increased owing to greater overall use of revascularization procedures.
Lipoprotein Particle Profiles by Nuclear Magnetic Resonance Compared With Standard Lipids and Apolipoproteins in Predicting Incident Cardiovascular Disease in Women
Authors: Mora Samia , Otvos James D. , Rifai Nader , Rosenson Robert S. , Buring Julie E. , Ridker Paul M
Published: February 2009

Background—

Nuclear magnetic resonance (NMR) spectroscopy measures the number and size of lipoprotein particles instead of their cholesterol or triglyceride content, but its clinical utility is uncertain.

Methods and Results—

Baseline lipoproteins were measured by NMR in 27 673 initially healthy women followed up for incident cardiovascular disease (n=1015) over an 11-year period. After adjustment for nonlipid risk factors, hazard ratios and 95% confidence intervals for the top versus the bottom quintile of NMR-measured lipoprotein particle concentration (measured in particles per liter) were 2.51 (1.91 to 3.30) for low-density lipoprotein (LDL
NMR
), 0.91 (0.75 to 1.12) for high-density lipoprotein (HDL
NMR
), 1.71 (1.38 to 2.12) for very low–density lipoprotein (VLDL
NMR
), and 2.25 (1.80 to 2.81) for the LDL
NMR
/HDL
NMR
ratio. Similarly adjusted results for NMR-measured lipoprotein particle size (measured in nanometers) were 0.64 (0.52 to 0.79) for LDL
NMR
size, 0.65 (0.51 to 0.81) for HDL
NMR
size, and 1.37 (1.10 to 1.70) for VLDL
NMR
size. Hazard ratios for NMR measures were comparable but not superior to standard lipids (total cholesterol 2.08 [1.63 to 2.67], LDL cholesterol 1.74 [1.40 to 2.16], HDL cholesterol 0.52 [0.42 to 0.64], triglycerides 2.58 [1.95 to 3.41], non-HDL cholesterol 2.52 [1.95 to 3.25], total/HDL cholesterol ratio 2.82 [2.23 to 3.58]) and apolipoproteins (B
100
2.57 [1.98 to 3.33], A-1 0.63 [0.52 to 0.77], and B
100
/A-1 ratio 2.79 [2.21 to 3.54]). Essentially no reclassification improvement was found with the addition of the LDL
NMR
particle concentration or apolipoprotein B
100
to a model that already included the total/HDL cholesterol ratio and nonlipid risk factors (net reclassification index 0% and 1.9%, respectively), nor did the addition of either variable result in a statistically significant improvement in the c-index.

Conclusions—

In this prospective study of healthy women, cardiovascular disease risk prediction associated with lipoprotein profiles evaluated by NMR was comparable but not superior to that of standard lipids or apolipoproteins.
Weekend Versus Weekday Admission and Mortality After Acute Pulmonary Embolism
Authors: Aujesky Drahomir , Jiménez David , Mor Maria K. , Geng Ming , Fine Michael J. , Ibrahim Said A.
Published: February 2009

Background—Optimal management of acute pulmonary embolism (PE) requires medical expertise, diagnostic testing, and therapies that may not be available consistently throughout the entire week. We sought to assess whether associations exist between weekday or weekend admission and mortality and length of hospital stay for patients hospitalized with PE.

Methods and Results—We evaluated patients discharged with a primary diagnosis of PE from 186 acute care hospitals in Pennsylvania (January 2000 to November 2002). We used random-effect logistic models to study the association between weekend admission and 30-day mortality and used discrete survival models to study the association between weekend admission and time to hospital discharge, adjusting for hospital (region, size, and teaching status) and patient factors (race, insurance, severity of illness, and use of thrombolytic therapy). Among 15 531 patient discharges with PE, 3286 patients (21.2%) had been admitted on a weekend. Patients admitted on weekends had a higher unadjusted 30-day mortality rate (11.1% versus 8.8%) than patients admitted on weekdays, with no difference in length of stay. Patients admitted on weekends had significantly greater adjusted odds of dying (odds ratio 1.17, 95% confidence interval 1.03 to 1.34) than patients admitted on weekdays. The higher mortality among patients hospitalized on weekends was driven by the increased mortality rate among the most severely ill patients.

Conclusions—Patients with PE who are admitted on weekends have a significantly higher short-term mortality than patients admitted on weekdays. Quality-improvement efforts should aim to ensure a consistent approach to the management of PE 7 days a week.
Leptin Is Associated With Blood Pressure and Hypertension in Women From the National Heart, Lung, and Blood Institute Family Heart Study
Authors: Ma Duanduan , Feitosa Mary F. , Wilk Jemma B. , Laramie Jason M. , Yu Kai , Leiendecker-Foster Catherine , Myers Richard H. , Province Michael A. , Borecki Ingrid B.
Published: February 2009

Leptin is a key neuroendocrine hormone regulating food intake, metabolism, and fat accumulation, and it may also affect blood pressure and contribute to hypertension through sympathetic activation in the vasculature or at the renal level. Although previous studies have shown that the distribution of leptin is significantly different between males and females, as is the risk of hypertension between males and females, results regarding the role of leptin in the gender-specific regulation of blood pressure are controversial. Thus, we performed family-based association analyses in the National Heart, Lung, and Blood Institute Family Heart Study to test the hypothesis that
LEPTIN
gene variants and the plasma leptin level influence variability in blood pressure and the risk of hypertension differently by gender. We identified significant associations between
LEPTIN
single nucleotide polymorphisms with blood pressure and hypertension, but in postmenopausal women only. We also identified significant associations between plasma leptin levels and both blood pressure and hypertension in women. The current study supports a role for
LEPTIN
and plasma leptin levels in blood pressure regulation in women. It also provides insight into the gender differences in hypertension, as well as the differential distribution and activity of leptin in men and women.
Targeted Expression of Receptor-Associated Late Transducer Inhibits Maladaptive Hypertrophy via Blocking Epidermal Growth Factor Receptor Signaling
Authors: Cai Jun , Yi Fang-Fang , Yang Long , Shen Di-Fei , Yang Qinling , Li Ankang , Ghosh Asish K. , Bian Zhou-Yan , Yan Ling , Tang Qi-Zhu , Li Hongliang , Yang Xin-Chun
Published: February 2009

Receptor-associated late transducer (RALT) is a feedback inhibitor of epidermal growth factor receptor signaling. RALT has been shown previously to be induced in the ischemic heart and to promote cardiomyocyte apoptosis in vitro. However, the role of RALT in cardiac hypertrophy remains unclear. We hypothesized that forced expression of RALT in the murine heart would protect the heart against cardiac hypertrophy in vivo. We investigated the effect of cardiac overexpression of rat RALT on cardiac hypertrophy induced by angiotensin II and isoproterenol in RALT transgenic mice and wild-type littermates. The extent of cardiac hypertrophy was assessed by 2D and M-mode echocardiography as well as by molecular and pathological analyses of cardiac samples. Constitutive expression of rat RALT in cardiac myocytes of murine heart attenuated both hypertrophic and inflammatory responses and preserved cardiac function. These beneficial effects were associated with the attenuation of the epidermal growth factor receptor–dependent cascade that was triggered by angiotensin II and isoproterenol stimulation. Additional evidence demonstrated that RALT expression blocked fibrosis in vivo and collagen synthesis in vitro. Therefore, cardiac overexpression of RALT improves cardiac function and inhibits maladaptive hypertrophy, inflammation, and fibrosis through attenuating epidermal growth factor receptor–dependent signaling.
Continued Improvement in Hypertension Management in England
Authors: Falaschetti Emanuela , Chaudhury Moushumi , Mindell Jennifer , Poulter Neil
Published: February 2009

This study evaluate whether blood pressure management has improved in England between 2003 and 2006, using cross-sectional, nationally representative, random samples of 8834 (in 2003) and 7478 (in 2006) noninstitutionalized adults (aged ≥16 years) of mean age 46 (in 2003) and 47 (in 2006) years. Overall mean blood pressure levels in 2006 were 130.8/74.2 mm Hg in men and 124.0/72.4 mm Hg in women. Awareness of hypertension increased significantly in the overall population (from 62% in 2003% to 66% in 2006;
P
<0.001), the increase being significant in women (from 64% in 2003% to 71% in 2006;
P
<0.001) but not in men (from 60% to 62%;
P
=0.26). Similarly, the proportion treated had risen significantly overall (from 48% to 54%;
P
<0.001) and in women (from 52% to 62%;
P
<0.001) but not in men (from 43% to 47%;
P
=0.05). Control rates (<140/90 mm Hg) were higher in 2006 than in 2003 (from 22% to 28%;
P
<0.001) and had increased more among women than men: from 23% to 32% in women (
P
<0.001) and from 21% to 24% in men (
P
=0.02). Among those on treatment, control rates increased from 46% to 52% (
P
<0.001; from 44% to 53% in women,
P
<0.001; and from 48% to 52% in men,
P
=0.18). The most common agents used for monotherapy have changed since 2003 and were angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Where ≥2 drugs were used, the most common antihypertensive class used varied by age and ethnicity. Awareness, treatment, and control of hypertension increased between 2003 and 2006, particularly in women, but opportunities for further improvement remain.
Association of Remote Hypertension in Pregnancy With Coronary Artery Disease
Authors: Valdés Gloria , Quezada Felipe , Marchant Eugenio , von Schultzendorff Astrid , Morán Sergio , Padilla Oslando , Martínez Alejandro
Published: February 2009

Because hypertensive pregnancies have been associated with increased cardiovascular disease, we aimed to identify whether angiographically characterized coronary artery disease differed in women with previous normotensive pregnancies or hypertensive pregnancies (HPs). The study group included 217 parous women, aged 60.9±9.2 (SD) years, who required coronary angiography between January 2006 and December 2007, 36.8±9.9 and 28.8±10.5 years after their first and last pregnancy, respectively; 146 had normotensive pregnancies and 71 had ≥1 HP, according to a questionnaire including reproductive history and cardiovascular risks. Body mass index, smoking, and frequency of diabetes were similar in both groups. Chronic hypertension (93% versus 78%;
P
=0.007), hyperlipidemia (82% versus 69%;
P
=0.049), and premature familial cardiovascular disease (42% versus 20%;
P
=0.001) prevailed in HPs. Participants with HPs were younger (58.9±8.3 versus 61.9±9.6 years;
P
=0.025) than participants with normotensive pregnancies. Although 49% of all participants had hemodynamically significant coronary artery disease (≥70% stenosis), no differences were observed between groups in the number of stenotic arteries; however, their number increased by 28% and 22% over a 10-year period in HPs and normotensive pregnancies, respectively (
P
=0.034). Multivariate analysis showed that HPs had a nonsignificant risk of having coronary artery disease (odds ratio: 1.21; 95% CI: 0.64 to 2.28), and being a current smoker (odds ratio: 4.13; 95% CI: 1.85 to 9.25), a diabetic (odds ratio: 2.29; 95% CI: 1.85 to 9.25), or having a family history of premature cardiovascular disease (odds ratio: 2.34; 95% CI: 1.17 to 2.39) significantly increased the risk of coronary artery disease. This study demonstrates that women with HPs have earlier coronary disease, probably related to intermediate cardiovascular risks that have a gestational expression.
Corrections on the Box Plots of the Coverage Metric in “Multiobjective Immune Algorithm with Nondominated Neighbor-based Selection”
Authors: Gong Maoguo , Jiao Licheng , Yang Dongdong
Published: February 2009

In this study, we analyze the experimental results in Gong et al. (2008), and find that the box plots of the coverage metric in solving the five three-objective problems are wrong. The corresponding corrected box plots are presented. The corrected results are still consistent with the original conclusions.
A Deeper Look at the Proportionality—Turnout Nexus
Authors: Selb Peter
Published: February 2009

Evidence that turnout is higher under proportional representation (PR) than in majoritarian elections is overwhelming. Yet previous research has largely failed to explain why. One line of argument maintains that higher turnout under PR is a by-product of larger party systems. However, a larger number of parties has been demonstrated to depress turnout. Alternatively, it is argued that majoritarian electoral systems tend to produce safe seats and that voters have little incentive to turn out there. Thus, uneven turnout over electoral districts due to variable intensities of local competition is made responsible for the lower overall turnout. Empirical evidence on this conjecture is scant. This article scrutinizes the relationship between electoral rules, competition, and turnout with district-level data from 31 national elections. Results from a heteroscedastic model indicate that lower net turnout in majoritarian systems is indeed a consequence of uneven turnout over districts due to variable levels of local competitiveness.
Market Reform as a Stimulus to Particularistic Politics
Authors: McMann Kelly M.
Published: February 2009

We know little about how market reform affects political development, especially citizens' behavior. Market reform advocates prescribe that citizens should reduce their reliance on the state, turn to nonstate actors for assistance, and obtain limited state goods and services through their membership in certain social categories, not their particular traits. An analysis of three mass surveys and 232 interviews the author conducted in Central Asia, along with additional data from 24 postcommunist countries, reveals that market reform can have effects opposite from those prescribed: Individuals may make particularistic demands of government officials instead of relying on nonstate actors. This occurs in countries where state economic intervention was substantial and where reforms reduced the state's economic role but failed to develop market-enhancing institutions. Under these conditions individuals informally seek resources from state officials because nonstate actors do not offer substitute resources, and market reform policies discourage reliance on the state.
Two Temples, Three Religions, and a Tourist Attraction
Authors: Xiaofei Kang
Published: February 2009

Huanglong (Yellow Dragon) in northwestern Sichuan province is an old multi ethnic pilgrimage site that has become a UNESCO World Nature Heritage Reserve and a major national tourist attraction since the 1990s. This article focuses on the controversy over the identity and restoration of two major temples in Huanglong and analyzes the interaction of contemporary China's religious revival and the development of tourism. As local state agencies seek to redefine the religious landscape of Huanglong in the service of both state hegemony and the market appeal of ethnic differences, they compete with Han Chinese lay Buddhists and Tibetan and Daoist monastic forces, each of whom take advantage of tourism to further their own religious and ethnic causes.
A Resilience Intervention in African American Adults With Type 2 Diabetes
Authors: Steinhardt Mary A. , Mamerow Madonna M. , Brown Sharon A. , Jolly Christopher A.
Published: February 2009

Purpose The purpose of this pilot study was to determine the feasibility of offering the authors' Diabetes Coaching Program (DCP), adapted for African Americans, in a sample of African American adults with type 2 diabetes.

Methods The study used a 1-group, pretest-posttest design to test the acceptance and potential effectiveness of the DCP. Subjects were a convenience sample of 16 African Americans (8 women, 8 men) with type 2 diabetes; 12 subjects (6 women, 6 men) completed the program. The DCP included 4 weekly class sessions devoted to resilience education and diabetes self-management, followed by 8 biweekly support group meetings. Psychosocial process variables (resilience, coping strategies, diabetes empowerment) and proximal (perceived stress, depressive symptoms, diabetes self-management) and distal outcomes (body mass index [BMI], fasting blood glucose, HbA1C, lipidemia, blood pressure) were assessed at baseline and at 6 months after study entry. Qualitative data were collected at 8 months via a focus group conducted to examine the acceptability of the DCP.

Results Preliminary paired t tests indicated statistically significant improvements in diabetes empowerment, diabetes self-management, BMI, HbA1c, total cholesterol, low-density lipoprotein cholesterol, and systolic and diastolic blood pressure. Medium to large effect sizes were reported. Resilience, perceived stress, fasting blood glucose, and high-density lipoprotein cholesterol improved, but changes were not statistically significant. Focus group data confirmed that participants held positive opinions regarding the DCP and follow-up support group sessions, although they suggested an increase in program length from 4 to 8 weeks.

Conclusions The pilot study documented the feasibility and potential effectiveness of the DCP to enhance diabetes empowerment, diabetes self-management, and reductions in the progression of obesity, type 2 diabetes, and cardiovascular disease in the African American community. Randomized experimental designs are needed to confirm these findings.
National Innovation System
Authors: Godin Benoît
Published: February 2009

In the late 1980s, a new conceptual framework appeared in the science, technology, and innovation studies: the National Innovation System. The framework suggests that the research system's ultimate goal is innovation, and that the system is part of a larger system composed of sectors such as government, university, and industry and their environment. The framework also emphasized the relationships between the components or sectors, as the ``cause'' that explains the performance of innovation systems. Most authors agree that the framework came from researchers like Freeman, Nelson, and Lundvall. In this article, the author want to go further back in time and show what the ``system approach'' owes to the Organisation for Economic Co-operation and Development (OECD) and its very early works from the 1960s. This article develops the idea that the system approach was fundamental to OECD work, and that, although not using the term National Innovation System as such, the organization considerably influenced the above-mentioned authors.
A pilot study of the effects of chronic paroxetine administration on hippocampal N-acetylaspartate in generalized anxiety disorder
Authors: Mathew SJ , Price RB , Shungu DC , Mao X. , Smith ELP , Amiel JM , Coplan JD
Published: February 2009

The neural basis of generalized anxiety disorder (GAD) is poorly characterized. The effect of chronic administration (12 weeks) of paroxetine, a selective serotonin reuptake inhibitor, on N-acetylaspartate (NAA), a marker of neuronal viability, was evaluated in adults with GAD using proton magnetic resonance spectroscopic imaging (1H MRSI) at 1.5 T. We hypothesized that, pretreatment abnormalities in hippocampal NAA/creatine (NAA/Cr) would normalize with symptomatic improvement. Nine GAD patients (mean age = 41.7 year; 4 females) received 12 weeks of open-label paroxetine treatment, flexibly dosed up to 60 mg/day. Clinical outcome was assessed with the Hamilton Anxiety Rating Scale (HAM-A). Multislice 1H MRSI scans were performed at unmedicated baseline and following 6 and 12 weeks of treatment. Ten untreated healthy volunteers (HVs) (mean age = 37.1 year; 4 females) received scans at the same intervals. All patients achieved remission (HAM-A ≤ 7) by week 12. Compared to HVs, GAD patients showed persistently lower levels of bilateral hippocampal NAA/Cr (17.7% mean decrease; Cohen’s d = 1.29) that were maintained across all three time points, despite marked symptom improvement. This pilot study failed to support an association between a hippocampal neuronal marker and anxiolytic response to paroxetine, and suggests further investigation of potential trait-like hippocampal abnormalities in GAD.
Planning Posttherapeutic Oncology Surveillance Visits Based on Individual Risk
Authors: Filleron T. , Barrett A. , Ataman O. , Kramar A.
Published: February 2009

The main objective of posttherapeutic surveillance in oncology is to detect recurrent disease associated with treatment failure. Current follow-up schedules are easy to apply because they are planned on a regular basis (for instance, every 3 months) but do not take into account prognostic factors associated with time to failure. We propose a 2-stage strategy to individualize surveillance by first identifying prognostic factors for time to failure, then modeling cumulative risk or cumulative incidence to plan visits according to equal quantiles of risk or probability of failure, respectively. Using data from a clinical trial of radiotherapy in non—small cell lung cancer patients, we demonstrate how this method could improve the early detection of relapse.
A Prospective Randomized Clinical Trial Comparing Arthroscopic Single-and Double-Row Rotator Cuff Repair
Authors: Burks Robert T. , Crim Julia , Brown Nick , Fink Barbara , Greis Patrick E.
Published: February 2009

Background

Double-row arthroscopic rotator cuff repair has become more popular, and some studies have shown better footprint coverage and improved biomechanics of the repair.

Hypothesis

Double-row rotator cuff repair leads to superior cuff integrity and early clinical results compared with single-row repair.

Study Design

Randomized controlled trial; Level of evidence, 1.

Methods

Forty patients were randomized to either single-row or double-row rotator cuff repair at the time of surgical intervention. Patients were followed with clinical measures (UCLA, Constant, WORC, SANE, ASES, as well as range of motion, internal rotation strength, and external rotation strength). Magnetic resonance imaging (MRI) studies were performed on each shoulder preoperatively, 6 weeks, 3 months, and 1 year after repair.

Results

Mean anteroposterior tear size by MRI was 1.8 cm. A mean of 2.25 anchors for single row (SR) and 3.2 for double row (DR) were used. There were 2 retears at 1 year in each group. There were 2 additional cases that had severe thinning in the DR repair group at 1 year. The MRI measurements of footprint coverage, tendon thickness, and tendon signal showed no significant differences between the 2 repair groups. At 1 year, there were no differences in any of the postoperative measures of motion or strength. At 1 year, mean WORC (SR, 84.8; DR, 87.9), Constant (SR, 77.8; DR, 74.4), ASES (SR, 85.9; DR, 85.5), UCLA (SR, 28.6; DR, 29.5), and SANE (SR, 90.9; DR, 89.9) scores showed no significant differences between groups.

Conclusions

No clinical or MRI differences were seen between patients repaired with a SR or DR technique.
A Prospective Study of Postconcussive Outcomes after Return to Play in Australian Football
Authors: Makdissi Michael , McCrory Paul , Ugoni Antony , Darby David , Brukner Peter
Published: February 2009

Background

Decisions regarding safe return to play after concussion in sport remain difficult.

Objective

To determine whether a concussed player returned to play using an individual clinical management strategy is at risk of impaired performance or increased risk of injury or concussion.

Study Design

Cohort study; Level of evidence, 3.

Methods

All elite Australian football players were followed for 4 seasons. Players were recruited into the study after sustaining a concussive injury. Outcome measures included performance statistics (disposals per hour match-time), injury rates, and recurrence of concussion on return to play. A subset of players had brief screening cognitive tests performed at baseline and after their concussion. Noninjured players matched for team, position, age, and size were chosen as controls.

Results

A total of 199 concussive injuries were observed in 158 players. Sixty-one concussive injuries were excluded from analysis because of incomplete data (45 players) or presence of concurrent injury (16 players). Of the 138 concussive injuries assessed, 127 players returned to play without missing a game (92%). The remainder of concussed players returned to play after missing a single game (8%). Overall, there was no significant decline in disposal rates in concussed players on return to competition. Furthermore, there were no significant differences in injury rates between concussed and team, position, and game-matched controls. In the subset of players who had completed screening cognitive tests, all had returned to their individual baseline performance before being returned to play.

Conclusion

Return to play decisions based on individual clinical assessment of recovery allows safe and appropriate return to sport following a concussive injury.
Does Operative Fixation of an Osteochondritis Dissecans Loose Body Result in Healing and Long-Term Maintenance of Knee Function?
Authors: Magnussen Robert A. , Carey James L. , Spindler Kurt P.
Published: February 2009

Background

Osteochondritis dissecans (OCD) can progress to loose body formation, resulting in a grade IV defect. The decision to fix versus excise the loose body is controversial. Published operative fixation outcomes are small case series with short follow-up.

Hypothesis

Operative fixation (ORIF) of the loose body into the grade IV defect will heal and approximate “normal” knee function at long-term follow-up.

Study Design

Case series; Level of evidence, 4.

Methods

Twelve patients were identified who underwent ORIF of a knee OCD loose body into the grade IV osteochondral defects ranging in size from 2.0 to 8.0 cm 2 (mean, 3.5 cm2). After 12 weeks, hardware was removed, and healing was assessed. Long-term outcomes were assessed with a Knee injury and Osteoarthritis Outcome Score (KOOS) and a Marx activity score.

Results

Arthroscopy for screw removal revealed stable healing in 92% (11 of 12) of patients. No patients required subsequent surgery for a loose body. At an average of 9.2 years’ follow-up (range, 3.8-15.8 years), 83% (10 of 12) of patients completed the KOOS. The KOOS subscale scores for pain (mean, 87.8; range, 67-100), other symptoms (mean, 81.8; range, 61-96), function in activities of daily living (mean, 93.1; range, 72-100), and sports and recreation function (mean, 74.0; range, 40-100) were not significantly lower than those of published age-matched controls. However the KOOS subscale score for knee-related quality of life (mean, 61.9; range, 31-88) was significantly lower (P = .003).

Conclusion

Operative fixation of grade IV OCD loose bodies results in stable fixation. At an average 9 years after surgery, patients did not have symptoms of osteoarthritis pain and had normal function in activities of daily life. However, patients reported significantly lower knee-related quality of life. Operative fixation of OCD loose bodies is a better alternative to lesion excision.
Inhibition of Anterior Tibial Translation or Axial Tibial Rotation Prevents Anterior Cruciate Ligament Failure during Impact Compression
Authors: Yeow Chen Hua , Rubab Shahbaz Khan , Lee Peter V. S. , Goh James C. H.
Published: February 2009

Background

Anterior cruciate ligament injury is prevalent in activities involving large and rapid landing impact loads.

Hypothesis

Inhibition of anterior tibial translation/axial tibial rotation forestalls the ligament from failing at the range of peak compressive load that can induce ligament failure when both factors are unrestrained.

Study Design

Controlled laboratory study.

Methods

Sixteen porcine knee specimens were mounted onto a material testing system at 70° of flexion and were divided into 4 test groups: impact compression without restraint (IC), anterior tibial translation restraint (ICA), axial tibial rotation restraint (ICR), and combination of both restraints (ICC). Compression was successively repeated with increasing actuator displacement until ligament failure or visible bone fracture was observed. During compression, rotational and translational joint data were obtained using a motion capture system.

Results

The IC group underwent ligament failure via femoral avulsion; the peak compressive force during failure ranged from 1.4 to 4.0 kN. The ICA, ICR, and ICC test groups developed visible bone fracture with the ligament intact; the peak compressive force during fracture ranged from 2.2 to 6.9 kN. Posterior femoral displacement and axial tibial rotation for the ICA and ICR groups, respectively, were significantly lower relative to the IC group ( P < .05). Both factors were substantially reduced in the ICC group, but peak compressive force was higher compared with the IC group ( P < .05).

Conclusion

Substantial inhibition of these factors in an impact setup, which can induce ligament failure with the factors unrestrained, was able to prevent failure.

Clinical Relevance

Adequate inhibition of anterior tibial translation and axial tibial rotation by knee bracing during injurious impact is necessary for effective ligament protection.