bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of vitronectin and plasminogen activator inhibitor-1 levels with the risk of metabolic syndrome and type 2 diabetes mellitus
Authors: Alessi Marie-Christine , Nicaud Viviane , Scroyen Ilse , Lange Celine , Saut Noemie , Fumeron Frederic , Marre Michel , Lantieri Olivier , Fontaine-Bisson Benedicte , Juhan-Vague Iréne , Balkau Beverley , Tregouet David-Alexandre , Morange Pierre-Emmanuel ,   D.E.S.I.R. Study Group
Published: July 2011

SummaryIt was the objective of this study to investigate the relation between vitronectin and plasminogen activator inhibitor (PAI)-1 plasma levels with nine-year incidences of the metabolic syndrome (MetS) and of type 2 diabetes mellitus (T2DM). Baseline plasma concentrations of vitronectin and PAI-1 were measured in 627 healthy participants from the prospective D.E.S.I.R. cohort who subsequently developed MetS (n=487) and T2DM (n=182) over a nine-year follow-up (42 presented both) and who were matched with two healthy control subjects each by use of a nested case-control design. Parameters composing the MetS explained about 20% of plasma vitronectin levels. An increase of one standard deviation of vitronectin was associated with increased risks of both the MetS (odds ratio [OR] = 1.21 [1.07 – 1.37], p = 0.003) and T2DM (OR = 1.24 [1.01 – 1.53], p = 0.045). Corresponding ORs for PAI-1 levels were 1.46 [1.27 – 1.68] (p < 10−4) and 1.40 [1.14 – 1.72] (p = 0.0012). However, the effects of vitronectin and PAI-1 levels on outcomes were not independent. The vitronectin–MetS association was restricted to individuals with low to modest PAI-1 levels (OR = 1.33 [1.14 – 1.54], p = 0.0003) while no association was observed in individuals with high PAI-1 levels (OR = 0.87 [0.68 – 1.10], p = 0.24), the test for interaction being highly significant (p = 0.0009). In conclusion, baseline plasma vitronectin is a marker of incident MetS at nine years. Its predictive ability for MetS and T2DM should not be assessed independently of PAI-1 levels.
Fibrinogen concentration and its role in CVD risk in black South Africans – effect of urbanisation
Authors: Maat Moniek , Jerling Johann , Hoekstra Tiny , Kruger Annamarie , Pieters Marlien 
Published: July 2011

SummaryThe aim of this study was to investigate correlates of fibrinogen concentration in black South Africans, as well as its association with cardiovascular disease (CVD) risk and whether urbanisation influences this association. A total of 1,006 rural and 1,004 urban black South Africans from the PURE study were cross-sectionally analysed. The association of fibrinogen with CVD risk was determined by investigating the association of fibrinogen with other CVD risk markers as well as with predicted CVD risk using the Reynolds Risk score. The rural group had a significantly higher fibrinogen concentration than the urban group, despite higher levels of risk factors and increased predicted CVD risk in the urban group. Increased levels of CVD risk factors were, however, still associated with increased fibrinogen concentration. Fibrinogen correlated significantly, but weakly, with overall predicted CVD risk. This correlation was stronger in the urban than in the rural group. Multiple regression analysis showed that a smaller percentage of the variance in fibrinogen is explained by the traditional CVD risk factors in the rural than in the urban group. In conclusion, fibrinogen is weakly associated with CVD risk (predicted overall risk as well with individual risk factors) in black South Africans, and is related to the degree of urbanisation. Increased fibrinogen concentration, in black South Africans, especially in rural areas, is largely unexplained, and likely not strongly correlated with traditional CVD-related lifestyle and pathophysiological processes. This does, however, not exclude the possibility that once increased, the fibrinogen concentration contributes to future development of CVD.
Twice daily dosing of aspirin improves platelet inhibition in whole blood in patients with type 2 diabetes mellitus and micro- or macrovascular complications
Authors: Spectre Galia , Arnetz Lisa , Östenson Claes-Göran , Brismar Kerstin , Li Nailin , Hjemdahl Paul 
Published: July 2011

SummaryThe efficacy of low-dose aspirin in type 2 diabetes mellitus (T2DM) has been questioned. We tested if twice daily dosing of aspirin would be more effective in T2DM, possibly due to increased platelet turnover. A randomised cross-over study compared 75 mg aspirin OD, 75 mg BID and 320 mg OD (≥2 week treatment periods) in 25 patients with T2DM and micro- or macrovascular complications. Platelet responses were examined by impedance aggregometry (WBA) and the IMPACT-R aspirin test in whole blood, light transmittance aggregometry in plateletrich plasma (LTA), and urinary 11-dehydro-thromboxane B2 (TxM). Aspirin 75 mg BID decreased arachidonic acid (AA)-induced WBA compared to 75 mg OD (9.7 ± 4.5 vs. 12.6 ± 3.5 ohm; p=0.003) or to 320 mg OD (11.5 ± 4.2 Ohms; p=0.049). WBA responses to collagen were similarly attenuated by BID or high dosing (by 12–14%; p=0.02 for both). The IMPACT-R showed a better response to 75 mg BID compared to 75 mg OD (p=0.049), but not to 320 mg OD. AA-induced aggregation by LTA was <6.5% on all occasions, with no differences between aspirin dosages. TxM was reduced after 320 mg OD (p=0.002), but not 75 mg BID (p=0.07). Reticulated platelets were highly correlated with mean platelet volume (MPV; r2=0.74, p<0.0001). Both markers for platelet turnover were correlated with AA-induced WBA, but neither identified patients who benefited from BID dosing dependably. In conclusion, twice daily dosing improved laboratory responses to aspirin in high risk T2DM patients. Studies of whether BID dosing of aspirin can improve clinical outcomes in such patients are of interest.
Sustained impact of electronic alerts on rate of prophylaxis against venous thromboembolism
Authors: Beeler Patrick , Kucher Nils , Blaser Jürg 
Published: July 2011

SummaryAdvanced electronic alerts (eAlerts) and computerised physician order entry (CPOE) increase adequate thromboprophylaxis orders among hospitalised medical patients. It remains unclear whether eAlerts maintain their efficacy over time, after withdrawal of continuing medical education (CME) on eAlerts and on thromboprophylaxis indications from the study staff. We analysed 5,317 hospital cases from the University Hospital Zurich during 2006–2009: 1,854 cases from a medical ward with eAlerts (intervention group) and 3,463 cases from a surgical ward without eAlerts (control group). In the intervention group, an eAlert with hospital-specific venous thromboembolism (VTE) prevention guidelines was issued in the electronic patient chart 6 hours after admission if no pharmacological or mechanical thromboprophylaxis had been ordered. Data were analysed for three phases: pre-implementation (phase 1), eAlert implementation with CME (phase 2), and post-implementation without CME (phase 3). The rates of thromboprophylaxis in the intervention group were 43.4% in phase 1 and 66.7% in phase 2 (p<0.001), and increased further to 73.6% in phase 3 (p=0.011). Early thromboprophylaxis orders within 12 hours after admission were more often placed in phase 2 and 3 as compared to phase 1 (67.1% vs. 52.1%, p<0.001). In the surgical control group, the thromboprophylaxis rates in the three phases were 88.6%, 90.7%, 90.6% (p=0.16). Advanced eAlerts may provide sustained efficacy over time, with stable rates of thromboprophylaxis orders among hospitalised medical patients.
Deletion of human GP1BB and SEPT5 is associated with Bernard-Soulier syndrome, platelet secretion defect, polymicrogyria, and developmental delay
Authors: Bartsch Ingrid , Sandrock Kirstin , Lanza Francois , Nurden Paquita , Hainmann Ina , Pavlova Anna , Greinacher Andreas , Tacke Uta , Barth Michael , Busse Anja , Oldenburg Johannes , Bommer Martin , Strahm Brigitte , Superti-Furga Andrea , Zieger Barbara 
Published: July 2011

SummaryThe bleeding disorder Bernard-Soulier syndrome (BSS) is caused by mutations in the genes coding for the platelet glycoprotein GPIb/IX receptor. The septin SEPT5 is important for active membrane movement such as vesicle trafficking and exocytosis in non-dividing cells (i.e. platelets, neurons). We report on a four-year-old boy with a homozygous deletion comprising not only glycoprotein Ibβ (GP1BB) but also the SEPT5 gene, located 5’ to GP1BB. He presented with BSS, cortical dysplasia (polymicrogyria), developmental delay, and platelet secretion defect. The homozygous deletion of GP1BB and SEPT5, which had been identified by PCR analyses, was confirmed by Southern analyses and denaturing HPLC (DHPLC). The parents were heterozygous for this deletion. Absence of GPIbβ and SEPT5 proteins in the patient’s platelets was illustrated using transmission electron microscopy. Besides decreased GPIb/IX expression, flow cytometry analyses revealedimpaired platelet granule secretion. Because the bleeding disorder was extremely severe, the boy received bone marrow transplantation (BMT) from a HLA-identical unrelated donor. After successful engraftment of BMT, he had no more bleedingepisodes. Interestingly, also his mental development improved strikingly after BMT. This report describes for the first time a patient with SEPT5 deficiency presenting with cortical dysplasia (polymicrogyria), developmental delay, and platelet secretion defect.
Progression of the Prothrombotic State in Aging Bmal1-Deficient Mice
Authors: Hemmeryckx Bianca , Van Hove Cor E. , Fransen Paul , Emmerechts Jan , Kauskot Alexandre , Bult Hidde , Lijnen H. Roger , Hoylaerts Marc F. 
Published: July 2011

Objective—
The goal of this study was to examine the functional relationship between aging endothelium and thrombogenicity in a mouse model of premature aging.

Methods and Results—

Coagulation tests and factors, blood cell counts, aorta endothelial function, aorta gene expression, and FeCl
3
-induced thrombosis in mesenteric blood vessels were analyzed in 10- to 30-week-old brain and muscle ARNT-like protein-1 (Bmal1)–deficient (knockout [KO]) mice and wild-type littermates. Ten-week-old KO mice manifested shortened prothrombin times (9.7 versus 11.3 seconds in wild-type) and elevated plasma fibrinogen (264 versus 172 mg/dL). At 30 weeks, factor VII (198% versus 149%), and platelet counts (2049 versus 1354 K/μL) were increased in KO mice. Gene deficiency reduced the vasoactive nitric oxide production at 10 and 30 weeks and tended to reduce and increase the protein expression of thrombomodulin and von Willebrand factor, respectively, with aging. Shortened venular and arteriolar occlusion times on FeCl
3
-induced injury in 10-week-old KO mice confirmed higher thrombogenicity, culminating in priapism, observed in 60% of 25- to 30-week-old KO males.

Conclusion—
Endothelial dysfunction and a hypercoagulable state cause early arterial and venous thrombogenicity in Bmal1 KO mice. With aging, progressive endothelial dysfunction, rising platelet counts, and high factor VII further enhance thrombogenicity, provoking priapism.
Essential Domains of A Disintegrin and Metalloprotease With Thrombospondin Type 1 Repeats-13 Metalloprotease Required for Modulation of Arterial Thrombosis
Authors: Xiao Juan , Jin Sheng-Yu , Xue Jing , Sorvillo Nicoletta , Voorberg Jan , Zheng X. Long 
Published: July 2011

Objective—
A disintegrin and metalloprotease with thrombospondin type 1 repeats-13 (ADAMTS13) inhibits platelet aggregation and arterial thrombosis by cleavage of von Willebrand factor. However, the structural components of ADAMTS13 required for inhibition of arterial thrombosis are not fully defined.

Methods and Results—

Using recombinant proteins and a murine model, we demonstrated that an ADAMTS13 variant truncated after either the eighth thrombospondin type 1 repeat or the spacer domain inhibits ferric chloride–induced arterial thrombosis in
ADAMTS13
−/−
mice with efficacy similar to that of full-length ADAMTS13. The results obtained from monitoring thrombus formation in carotid and mesenteric arteries were highly concordant. Further analyses by site-directed mutagenesis and human monoclonal antibody inhibition assay revealed that the Cys-rich and spacer domains of ADAMTS13, particularly the amino acid residues between Arg559 and Glu664 in the spacer domain, may be critical for modulation of arterial thrombosis in vivo. Finally, the thrombosis-modulating function of ADAMTS13 and variants/mutants was highly correlated with the von Willebrand factor–cleavage activity under fluid shear stress.

Conclusion—
Our results suggest that the amino terminus of ADAMTS13, specifically the variable region of the spacer domain, is crucial for modulation of arterial thromboses under (patho)physiological conditions. These findings shed more light on the structure-function relationship of ADAMTS13 in vivo and may be applicable for rational design of protein- or gene-based therapy of arterial thromboses.
Serum Low-Density Lipoprotein Cholesterol Level Predicts Hematoma Growth and Clinical Outcome After Acute Intracerebral Hemorrhage
Authors: Rodriguez-Luna David , Rubiera Marta , Ribo Marc , Coscojuela Pilar , Pagola Jorge , Piñeiro Socorro , Ibarra Bernardo , Meler Pilar , Maisterra Olga , Romero Francisco , Alvarez-Sabin Jose , Molina Carlos A. 
Published: July 2011

Background and Purpose—
Lower serum low-density lipoprotein cholesterol (LDL-C) levels have been associated with increased risk of death after intracerebral hemorrhage (ICH). Nevertheless, their link with hematoma growth (HG) is unknown. Therefore, we aimed to investigate the relationship between LDL-C levels, HG, and clinical outcome in patients with acute ICH.

Methods—
We prospectively studied 108 consecutive patients with primary supratentorial ICH presenting within 6 hours from symptoms onset. National Institutes of Health Stroke Scale score and ICH volume on computed tomography scan were recorded at baseline and at 24 hours. Lipid profile was obtained during the first 24 hours. Significant HG was defined as hematoma enlargement >33% or >6 mL at 24 hours. Early neurological deterioration as well as mortality and poor long-term outcome (modified Rankin Scale score >2) at 3 months were recorded.

Results—

Although LDL-C levels were not correlated with ICH volume (
r
=−0.18;
P
=0.078) or National Institutes of Health Stroke Scale score (
r
=−0.17;
P
=0.091) at baseline, lower LDL-C levels were associated with HG (98.1±33.7 mg/dL versus 117.3±25.8 mg/dL;
P
=0.003), early neurological deterioration (89.2±31.8 mg/dL versus 112.4±29.8 mg/dL;
P
=0.012), and 3-month mortality (94.9±37.4 mg/dL versus 112.5±28.5 mg/dL;
P
=0.029), but not with poor long-term outcome (109.5±31.3 mg/dL versus 108.3±30.5 mg/dL;
P
=0.875). Moreover, LDL-C levels were inversely related to the amount of hematoma enlargement at 24 hours (
r
=−0.31;
P
=0.004). In multivariate logistic regression analysis, LDL-C level <95 mg/dL emerged as an independent predictor of HG (OR, 4.24; 95% CI, 1.26–14.24;
P
=0.020), early neurological deterioration (OR, 8.27; 95% CI, 1.66–41.16;
P=
0.010), and 3-month mortality (OR, 6.34; 95% CI, 1.29–31.3;
P
=0.023).

Conclusions—
Lower serum LDL-C level independently predicts HG, early neurological deterioration, and 3-month mortality after acute ICH.
Cilostazol, Not Aspirin, Reduces Ischemic Brain Injury via Endothelial Protection in Spontaneously Hypertensive Rats
Authors: Oyama Naoki , Yagita Yoshiki , Kawamura Miki , Sugiyama Yukio , Terasaki Yasukazu , Omura-Matsuoka Emi , Sasaki Tsutomu , Kitagawa Kazuo 
Published: July 2011

Background and Purpose—
It is well-established that hypertension leads to endothelial dysfunction in the cerebral artery. Recently, cilostazol has been used for the secondary prevention of ischemic stroke. Among antiplatelet drugs, phosphodiesterase inhibitors including cilostazol have been shown to have protective effects on endothelial cells. The aim of the present study is to investigate the effects of cilostazol and aspirin on endothelial nitric oxide synthase (eNOS) phosphorylation in the cerebral cortex, endothelial function, and infarct size after brain ischemia in spontaneously hypertensive rats (SHR).

Methods—

Five-week-old male SHR received a 5-week regimen of chow containing 0.1% aspirin, 0.1% cilostazol, 0.3% cilostazol, or the vehicle control. The levels of total and Ser
1177
-phosphorylated eNOS protein in the cerebral cortex were evaluated by Western blot. To assess the contribution of eNOS in maintaining cerebral blood flow, we monitored cerebral blood flow by laser-Doppler flowmetry after L-N
5
-(1-iminoethyl)ornithine infusion. Additionally, we evaluated residual microperfusion using fluorescence-labeled serum protein and infarct size after transient focal brain ischemia.

Results—

In SHR, the blood pressure and heart rate were similar among the groups. Cilostazol-treated SHR had a significantly higher ratio of phospho-eNOS/total eNOS protein than vehicle-treated and aspirin-treated SHR. Treating with cilostazol, but not aspirin, significantly improved cerebral blood flow response to L-N
5
-(1-iminoethyl)ornithine. Cilostazol also increased residual perfusion of the microcirculation and reduced brain damage after ischemia compared to vehicle control and aspirin.

Conclusions—
These findings indicate that cilostazol, but not aspirin, can attenuate ischemic brain injury by maintaining endothelial function in the cerebral cortex of SHR.
Trends in Pregnancy Hospitalizations That Included a Stroke in the United States From 1994 to 2007
Authors: Kuklina Elena V. , Tong Xin , Bansil Pooja , George Mary G. , Callaghan William M. 
Published: July 2011

Background and Purpose—
Stroke is an important contributor to maternal morbidity and mortality, but there are no recent data on trends in pregnancy-related hospitalizations that have involved a stroke. This report describes stroke hospitalizations for women in the antenatal, delivery, and postpartum periods from 1994 to 1995 to 2006 to 2007 and analyzes the changes in these hospitalizations over time.

Methods—
Hospital discharge data were obtained from the Nationwide Inpatient Sample, developed as part of the Healthcare Cost and Utilization Project sponsored by the Agency for Healthcare Research and Quality. Pregnancy-related hospitalizations with stroke were identified according to the International Classification of Diseases, Ninth Revision. All statistical analyses accounted for the complex sampling design of the data source.

Results—
Between 1994 to 1995 and 2006 to 2007, the rate of any stroke (subarachnoid hemorrhage, intracerebral hemorrhage, ischemic stroke, transient ischemic attack, cerebral venous thrombosis, or unspecified) among antenatal hospitalizations increased by 47% (from 0.15 to 0.22 per 1000 deliveries) and among postpartum hospitalizations by 83% (from 0.12 to 0.22 per 1000 deliveries) while remaining unchanged at 0.27 for delivery hospitalizations. In 2006 to 2007, ≈32% and 53% of antenatal and postpartum hospitalizations with stroke, respectively, had concurrent hypertensive disorders or heart disease. Changes in the prevalence of these 2 conditions from 1994 to 1995 to 2006 to 2007 explained almost all of the increase in postpartum hospitalizations with stroke during the same period.

Conclusions—
Our results have demonstrated an increasing trend in the rate of pregnancy-related hospitalizations with stroke in the United States, especially during the postpartum period, from 1994 to 1995 to 2006 to 2007.
Sex-Specific Temporal Trends in In-Hospital Mortality After Stroke Among Middle-Age Individuals in the United States
Authors: Towfighi Amytis , Tai Waimei , Markovic Daniela , Ovbiagele Bruce 
Published: July 2011

Background and Purpose—
Recent studies have revealed an increase in stroke prevalence among middle-aged women in the United States. To determine whether this is due to improved survival, we assessed temporal trends in sex-specific in-hospital mortality after stroke.

Methods—
Individuals aged 35 to 64 years hospitalized in 1997 to 2006 with a primary discharge diagnosis of stroke (N=2 537 097) in the United States were identified by the Nationwide Inpatient Sample. Temporal trends in sex-specific mortality after stroke and sex differences in mortality were assessed, before and after controlling for covariates.

Results—
From 1997 to 2006, poststroke mortality decreased in both men (6.06% to 5.15%) and women (6.02% to 4.88%) aged 35 to 64 years. Unadjusted analysis revealed that women aged 35 to 44 years (odds ratio=0.89; 95% CI, 0.83 to 0.95) and 45 to 54 years (odds ratio=0.93; 95% CI, 0.89 to 0.97) had lower mortality compared with men, whereas women aged 55 to 64 years had similar mortality compared with men. After adjustment for covariates, stroke type accounted for the better survival in women aged 35 to 44 years. After adjustment for covariates, women aged 45 to 54 years persistently had better survival than did men. Women aged 55 to 64 years had better survival than did men, once race and insurance type were accounted for.

Conclusions—
This study revealed a decline in stroke mortality rates from 1997 to 2006 among individuals aged 35 to 64 years. Better survival among women compared with men aged 35 to 54 years may partially explain the sex disparity in stroke prevalence.
Impact of Hospital Admission During Nonworking Hours on Patient Outcomes After Thrombolysis for Stroke
Authors: Haeusler Karl Georg , Gerischer Lea M. , Vatankhah Bijan , Audebert Heinrich J. , Nolte Christian H. 
Published: July 2011

Background and Purpose—
Whether the time of hospital admission is relevant for short-term outcome after stroke is under debate and may depend on care facilities.

Methods—
We retrospectively analyzed medical records from patients who received thrombolytic therapy within 4.5 hours of stroke onset in a stroke unit of the Charité–University Hospital Berlin (Charité; n=291) or within the stroke telemedicine (TEMPiS) network, comprising 12 community hospitals with telestroke units in Bavaria (n=616).

Results—

Thrombolytic therapy was administered during nonworking hours in 59.5% (Charité) and 55.0% (TEMPiS) of patients. A trend toward a lower rate of symptomatic intracranial hemorrhage (3.4% versus 9.2%;
P
=0.053), clinical worsening (11.9% versus 19.7%;
P
=0.079), and 7-day mortality (3.4% versus 8.7%;
P
=0.073) after admission during working hours was seen at Charité. However, multivariable analysis did not show a significant impact of the time of admission on clinical worsening, symptomatic intracranial hemorrhage, or 7-day mortality in both cohorts. Thrombolysis based on brain computed tomography instead of magnetic resonance imaging (odds ratio=4.98, 95% CI, 1.09 to 22.7) and more severe National Institutes of Health Stroke Scale score on admission (odds ratio=1.15 per point; 95% CI, 1.07 to 1.24) were associated with 7-day mortality at Charité. National Institutes of Health Stroke Scale score on admission (odds ratio=1.13 per point; 95% CI, 1.06 to 1.19) and older age (odds ratio=1.05 per year; 95% CI, 1.004 to 1.09) were correlated with 7-day mortality in TEMPiS. National Institutes of Health Stroke Scale on admission was the only independent predictor of symptomatic intracranial hemorrhage or clinical worsening in both cohorts.

Conclusions—
The majority of stroke patients received thrombolysis during nonworking hours. The time of hospital admission did not significantly influence the short-term outcome after thrombolysis.