bluuebunny/crossref_metadata_2025 huggingface dataset:
Diastolic Dysfunction Is Associated with Insulin Resistance, but Not with Aldosterone Level in Normotensive Offspring of Hypertensive Families
Authors: Žižek Bogomir , Poredoš Pavel , Trojar Andrej , Željko Tadej
Published: February 2008

Background and Aims: We investigated left ventricular (LV) morphology and function in association with insulin level/insulin resistance (IR) and aldosterone level in normotensive offspring of subjects with essential hypertension (familial trait, FT). Methods: The study encompassed 76 volunteers of whom 44 were normotensive with FT (aged 28–39 years) and 32 age-matched controls without FT. LV mass and function were measured using conventional echocardiography and tissue Doppler imaging. LV diastolic function was reported as peak septal annular velocities (Em and Em/Am ratio) in tissue Doppler imaging. Fasting insulin and aldosterone were determined. Results: In subjects with FT, the LV mass was higher than in controls (92.14 ± 24.02 vs. 70.08 ± 20.58 g; p < 0.001). The study group had a worse LV diastolic function than control subjects (lower Em and Em/Am ratio; p < 0.001). In subjects with FT, the Em/Am ratio was independently associated with IR (partial p = 0.029 in multivariate model, R2 = 0.51), but not with LV mass. The aldosterone level was comparable in both groups. Conclusions: In normotensive individuals with FT, LV morphological and functional abnormalities were found. LV dysfunction but not an increase in LV mass is associated with IR. The aldosterone level is probably not responsible for the development of early hypertensive heart disease.
Atrial Fibrillation following Device Closure of Patent Foramen Ovale
Authors: Burow Annika , Schwerzmann Markus , Wallmann Dieter , Tanner Hildegard , Sakata Takao , Windecker Stephan , Meier Bernhard , Delacrétaz Etienne
Published: February 2008

Objectives: Recurrent embolic events after device closure of patent foramen ovale (PFO) have been related to incomplete closure. Another cause could be atrial fibrillation (AF). The aim of this study was to determine the incidence of AF in stroke patients after PFO closure. Methods: Consecutive patients with device closure of a PFO after a stroke or transient ischemic attack and control patients with stroke underwent 7-day event loop recordings 3 and 6 months after PFO closure or stroke, respectively. Results: Forty patients treated by PFO device closure 96 ± 68 days after cryptogenic ischemic stroke and 70 control patients with ischemic stroke of other etiologies (known AF excluded) were compared. AF was identified in 6 patients (15%) of the treated group and in 12 control patients (17%, p = 0.77). In multivariate analysis, the presence of an occluder device was not an independent risk factor for AF. Conclusions: The incidence of AF is high after device closure of a PFO in stroke patients and similar to that in patients with stroke of non-PFO etiology and, hence, with no device. Further studies are required to determine the risk of thromboembolism and the optimal treatment in patients developing AF after device closure of a PFO.
Determinants of Endothelial Function in a Cohort of Patients with Peripheral Artery Disease
Authors: Golledge J. , Leicht A.S. , Crowther R.G. , Glanville S. , Clancy P. , Sangla K.S. , Spinks W.L. , Quigley F.
Published: February 2008

Objectives: Endothelial dysfunction assessed by brachial artery flow-mediated dilatation (FMD) has been associated with cardiovascular events. There have been relatively few studies examining FMD or other measures of endothelial function in patients with peripheral artery disease (PAD). The aim of this study was to examine determinants of FMD in a homogenous cohort of patients with PAD. Methods: We prospectively assessed patients presenting with life style-limiting intermittent claudication to establish the presence of cardiovascular risk factors, obesity and metabolic syndrome. Fasting serum was assayed for lipids, C-reactive protein, adiponectin, leptin, resistin and osteoprotegerin (OPG). FMD was measured by high-resolution ultrasound. Results: Serum concentrations of OPG were elevated in patients with obesity and metabolic syndrome. FMD was impaired in patients with obesity and metabolic syndrome and negatively correlated with serum concentrations of OPG. By multiple regression analysis, metabolic syndrome was independently associated with impaired FMD after adjustment for age, smoking, ischaemic heart disease, cerebrovascular disease and severity of PAD. Conclusions: Our findings suggest that metabolic syndrome is an important determinant of endothelial function in patients with PAD, and OPG may be a useful biomarker of this effect.
Biphasic versus Monophasic Shock for External Cardioversion of Atrial Flutter
Authors: Mortensen Kai , Risius Tim , Schwemer Tjark F. , Aydin Muhammet Ali , Köster Ralf , Klemm Hanno U. , Lutomsky Boris , Meinertz Thomas , Ventura Rodolfo , Willems Stephan
Published: February 2008

Background: External cardioversion is effective to terminate persistent atrial flutter. Biphasic shocks have been shown to be superior to monophasic shocks for ventricular defibrillation and atrial fibrillation cardioversion. The purpose of this trial was to compare the efficacy of rectilinear biphasic versus standard damped sine wave monophasic shocks in symptomatic patients with typical atrial flutter. Methods: 135 consecutive patients were screened, 95 (70 males, mean age 62 ± 13 years) were included. Patients were randomly assigned to a monophasic or biphasic cardioversion protocol. Forty-seven patients randomized to the monophasic protocol received sequential shocks of 100, 150, 200, 300 and 360 J. Forty-eight patients with the biphasic protocol received 50, 75, 100, 150 or 200 J. Results: First-shock efficacy with 50-Joule, biphasic shocks (23/48 patients, 48%) was significantly greater than with the 100-Joule, monophasic waveform (13/47 patients, 28%, p = 0.04). The cumulative second-shock efficacy with the 50- and 75-Joule, biphasic waveform (39/48 patients, 81%) was significantly greater than with the 100- and 150-Joule, monophasic waveform (25/47 patients, 53%, p < 0.05). The cumulative efficacy for the higher energy levels showed naturally no significant difference between the two groups. The amount of the mean delivered energy was significantly lower in the biphasic group (76 ± 39 J) compared to the monophasic one (177 ± 78 J, p < 0.05). Conclusions: For transthoracic cardioversion of typical atrial flutter, biphasic shocks have greater efficacy and the mean delivered current is lower than for monophasic shocks. Therefore, biphasic cardioversion with lower starting energies should be recommended.
High Prevalence of Risk Factors in Coronary Artery Disease in EUROPA Gives HOPE for ACE Inhibitors after PEACE
Authors: Pedersen Sune A. , Galatius Søren , Hecht Olsen Michael , Kühn Madsen Bente , Kyst Madsen Jan , Nielsen Olav W.
Published: February 2008

Background: Routine use of ACE inhibitors (ACE-I) as secondary preventive therapy for all patients with coronary artery disease (CAD) is challenged by the PEACE trial. Currently it is unclear to what extent ACE-I should be used in CAD populations. Purpose: To analyze the prevalence of left ventricular systolic dysfunction, diabetes, myocardial infarction and hypertension in an unselected and consecutive population of patients with documented CAD and evaluate the potential need for ACE-I treatment in a real-life scenario. Methods: We searched a database containing all invasive cardiac investigations in three hospitals in Copenhagen from July 1, 2000 to June 30, 2003. Patients with no angiographic sign of CAD were excluded. Results: Among 7,345 patients, 4,180 had stable CAD and 3,165 had acute coronary syndrome (ACS). Among the stable CAD patients 78% had at least one of the following indications for treatment with an ACE-I: left ventricular ejection fraction <0.45 (20%), hypertension (39%), diabetes (19%), systolic blood pressure >159 mm Hg (21%), and/or myocardial infarction (42%). Among ACS patients, 90% had an indication for ACE-I treatment. Conclusion: Depending on the definitions, at least 78% of the patients with stable CAD and 90% with ACS have an accepted indication for treatment with an ACE-I.
Impact of All-Day Physical Activity on Ventilatory Perfusion Coupling in Patients Undergoing Cardiac Resynchronization Therapy
Authors: Berger Thomas , Zwick Ralf Harun , Poelzl Gerhard , Hoertnagl Helmut , Pachinger Otmar , Stuhlinger Markus , Roithinger Franz Xaver , Hintringer Florian
Published: February 2008

Objectives: There is still little information about the cardiorespiratory effects of cardiac resynchronization therapy (CRT) in patients undergoing all-day physical activity. This study aimed to assess the effects of CRT on ventilatory perfusion coupling during submaximal exercise. Methods: Metabolic and hemodynamic parameters were obtained during treadmill exercise testing as well as during rest for each single-right (RV), -left (LV) and biventricular (BiV) pacing mode as well as during intrinsic conduction (VVI 30) in 37 patients. Only responders to CRT (>10% increase in cardiac output (CO) during BiV pacing; n = 27) were included into the evaluation. Results: LV and BiV pacing increased systolic (144 ± 25 and 142 ± 28 vs. 118 ± 29 mm Hg, p < 0.05) and mean blood pressure (108 ± 19 and 109 ± 19 vs. 94 ± 25 mm Hg, p < 0.05) as well as CO (7.0 ± 0.6 and 7.2 ± 0.8 vs. 6.0 ± 0.6 l/min, p < 0.05 and p < 0.01) during exercise as compared to VVI 30. Simultaneously, LV and BiV pacing decreased dead space ventilation (18 ± 3 and 17 ± 3 vs. 20 ± 4, p < 0.01) and the ventilatory equivalent for oxygen (31 ± 4 and 31 ± 5 vs. 36 ± 6; p < 0.05) compared to intrinsic conduction. Conclusion: The improvement in ventilatory efficacy during CRT, which is demonstrated by the decrease in the ventilatory equivalent for oxygen, results from an increase in CO and thus from a reduction in the ventilatory perfusion mismatch.
Public Health Impact of Hearing Impairment and Disability
Authors: Kotby M.N. , Tawfik S. , Aziz A. , Taha H.
Published: February 2008

This presentation of the public health impact of hearing impairment highlights the important elements of interaction between the disability and community. Objectives: Retrospective study to identify the size of the problem of hearing loss, illustrating not only the magnitude but also the serious effect of the lack of reliable data concerning this matter. It highlights the challenges met within a mid-economy community regarding the handling of the impact of the disability. The Egyptian data is given as an example of the situation in a mid-economy community. Study Design: A brief introduction of some epidemiological factors of hearing impairment is presented including the size of the problem in Egypt. Data of the neonatal hearing screening program of the Audiology Unit, Ain Shams University, is presented. The impact of the disability is then discussed in relation to the age of onset and the degree and type of hearing loss. This is followed by the description of the nature and effect of the disability in the different age groups. A discussion of the various factors that may modify the capability of the community to deal with such disability follows. This includes various economic indices with their possible limitations on the part of the community. Such a briefing illustrates the challenges met in the rehabilitation of the deaf and the hearing-impaired in a developing mid-economy country. The broad lines of the management of the problem both at the prophylactic as well as the rehabilitative levels are discussed. A final remark on recommendations and possible future development in a developing country is presented.
Caki-1 Cells as a Model System for the Interaction of Renally Secreted Drugs with OCT3
Authors: Glube Natalie , Langguth Peter
Published: February 2008

Background/Aims: Organic cation transporters (OCT) in the proximal tubules (PTs) participate in the renal secretion of several therapeutic agents. The exact role of OCT3 in renal secretion remains undetermined, partially due to the lack of an appropriate in vitro model system. The current work introduces the PT representative cell line, Caki-1, as a model system for studying the involvement of OCT3 in renal secretion. Methods: Caki-1 cells were characterized for OCT3 expression via real-time RT-PCR and immunocytochemical staining techniques. Uptake kinetics of OCT3 in Caki-1 cells was determined using prototypical substrates and inhibitors. Inhibition of OCT3-mediated uptake via several renally secreted drugs and those specifically of quaternary ammonium structure were determined. Results: OCT3 expression was confirmed at the gene level and subcellular localization to the basolateral membrane (BLM) was illustrated for the first time. Caki-1 cells exhibited trademark kinetics of OCT3 and interacted with all therapeutic agents tested with varying affinities. The apparent IC50 values for cimetidine and trimethoprim were pharmacologically relevant. Conclusion: Confirmation for the usefulness of Caki-1 cells as a PT model system for investigations of OCT3 was obtained, a novel BLM localization of OCT3 was possible and relevant interactions between OCT3 and renally secreted drugs were shown.
Lymphocyte Subsets and the Role of Th1/Th2 Balance in Stressed Chronic Pain Patients
Authors: Kaufmann Ines , Eisner Christoph , Richter Peter , Huge Volker , Beyer Antje , Chouker Alexander , Schelling Gustav , Thiel Manfred
Published: February 2008

Background: The complex regional pain syndrome (CRPS) and fibromyalgia (FM) are chronic pain syndromes occurring in highly stressed individuals. Despite the known connection between the nervous system and immune cells, information on distribution of lymphocyte subsets under stress and pain conditions is limited. Methods: We performed a comparative study in 15 patients with CRPS type I, 22 patients with FM and 37 age- and sex-matched healthy controls and investigated the influence of pain and stress on lymphocyte number, subpopulations and the Th1/Th2 cytokine ratio in T lymphocytes. Results: Lymphocyte numbers did not differ between groups. Quantitative analyses of lymphocyte subpopulations showed a significant reduction of cytotoxic CD8+ lymphocytes in both CRPS (p < 0.01) and FM (p < 0.05) patients as compared with healthy controls. Additionally, CRPS patients were characterized by a lower percentage of IL-2-producing T cell subpopulations reflecting a diminished Th1 response in contrast to no changes in the Th2 cytokine profile. Conclusions: Future studies are warranted to answer whether such immunological changes play a pathogenetic role in CRPS and FM or merely reflect the consequences of a pain-induced neurohumoral stress response, and whether they contribute to immunosuppression in stressed chronic pain patients.
Competing Risk Factor Analysis of End-Stage Renal Disease and Mortality in Chronic Kidney Disease
Authors: Agarwal Rajiv , Bunaye Zerihun , Bekele Dagim M. , Light Robert P.
Published: February 2008

Background: Death and dialysis are competing outcomes in patients with chronic kidney disease (CKD). The factors associated with end-stage renal disease (ESRD) versus death in this population are unknown. The purpose of our study was to evaluate the competing risk of ESRD versus mortality and to evaluate the risk factors associated with these two outcomes. Methods: We prospectively recruited 220 consecutive patients at a Veterans Administration Medical Center attending a renal clinic who met the definition of CKD (estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 or urine protein/creatinine ratio of >0.22 g/g). Using age, race, proteinuria, eGFR, systolic blood pressure, and coronary artery disease as predictors, we calculated the competing end-points of ESRD or death using a competing Cox regression model. Results: The cumulative incidence for ESRD was 17.6% and death 18.5% during follow-up that lasted up to 7 years. ESRD was predicted by younger age (hazard ratio (HR) 0.91/year), black race (HR 2.75), higher systolic blood pressure (HR 1.02/mm Hg), proteinuria (HR 1.37/log urine protein/creatinine ratio) and low eGFR (0.014/log eGFR ml/min/1.73 m2). Death was predicted by older age (HR 1.07/year), lower eGFR (HR 0.43/log eGFR ml/min/1.73 m2), proteinuria (HR 1.26/log urine protein/creatinine ratio) and coronary artery disease (HR 2.52). The coefficients were statistically different for age (p < 0.001), log eGFR (p < 0.001) and systolic blood pressure (p = 0.04) for ESRD and death outcomes. Conclusions: The risk for mortality is similar to the risk of ESRD in the CKD population of veterans seen by nephrologists. Risk factors for ESRD and death appear to differ in this population. Certain clinical and demographic factors may discriminate between the end-points of death or dialysis and may influence decisions about planning for ESRD.
Inhibition of Plasminogen Activator Inhibitor-1
Authors: Izuhara Yuko , Takahashi Satoru , Nangaku Masaomi , Takizawa Shunya , Ishida Hideyuki , Kurokawa Kiyoshi , van Ypersele de Strihou Charles , Hirayama Noriaki , Miyata Toshio
Published: February 2008

Objective—Serine protease inhibitors (serpin) play a central role in various pathological processes including coagulation, fibrinolysis, malignancy, and inflammation. Inhibition of serpins may prove therapeutic. As yet, however, only very few small molecule serpin inhibitors have been reported. For the first time, we apply a new approach of virtual screening to discover novel, orally active, small molecule serpin inhibitors and report their effectiveness.

Methods and Results—We focused on a clinically important serpin, plasminogen activator inhibitor-1 (PAI-1), whose crystal structure has been described. We identify novel, orally active molecules able to enter into the strand 4 position (s4A) of the A β-sheet of PAI-I as a mock compound. In vitro they specifically inhibit the PAI-1 activity and enhance fibrinolysis activity. In vivo the most effective molecule (TM5007) inhibits coagulation in 2 models: a rat arteriovenous (AV) shunt model and a mouse model of ferric chloride–induced testicular artery thrombosis. It also prevents the fibrotic process initiated by bleomycin in mouse lung.

Conclusions—The present study demonstrates beneficial in vitro and in vivo effects of novel PAI-1 inhibitors. Our methodology proves to be a useful tool to obtain effective inhibitors of serpin activity.
Ex Vivo Priming of Endothelial Progenitor Cells With SDF-1 Before Transplantation Could Increase Their Proangiogenic Potential
Authors: Zemani Faouzia , Silvestre Jean-Sébastien , Fauvel-Lafeve Françoise , Bruel Arlette , Vilar José , Bieche Ivan , Laurendeau Ingrid , Galy-Fauroux Isabelle , Fischer Anne Marie , Boisson-Vidal Catherine
Published: February 2008

Objectives—

As SDF-1 and its cognate receptor CXCR4 play a key role in the survival and mobilization of immature cells, we examined whether preconditioning of endothelial progenitor cells (EPCs) with SDF-1 could further promote their capacity to enhance angiogenesis.

Methods and Results—

EPC exposure to 100 ng/mL SDF-1 for 30 min induced a proangiogenic phenotype, with cell migration and differentiation into vascular cords in Matrigel and increased their therapeutic potential in a nude mouse model of hindlimb ischemia. This pretreatment enhanced EPC adhesion to activated endothelium in physiological conditions of blood flow by stimulating integrin-mediated EPCs binding to endothelial cells. Pretreated EPCs showed significantly upregulated surface α4 and αM integrin subunit expression involved in the homing of immature cells to a neovasculature and enhanced FGF-2 and promatrix metalloproteinase (MMP)-2 secretion. All these effects were significantly attenuated by EPC incubation with AMD-3100, a CXCR4 antagonist, by prior HSPGs disruption and by HUVEC incubation with anti–intercellular adhesion molecule1 (ICAM-1) and anti–vascular cell adhesion molecule (VCAM) blocking antibodies. Pretreated EPCs adhered very rapidly (within minutes) and were resistant to shear stresses of up to 2500s
−1
.

Conclusions—

SDF-1 pretreatment during EPC expansion stimulates EPC adhesion to endothelial cells and thus augments the efficiency of cell therapy for ischemic vascular diseases.
Dimethylarginine Dimethylaminohydrolase Overexpression Enhances Insulin Sensitivity
Authors: Sydow Karsten , Mondon Carl E. , Schrader Joerg , Konishi Hakuoh , Cooke John P.
Published: February 2008

Objective—

Previous studies suggest that nitric oxide (NO) may modulate insulin-induced uptake of glucose in insulin-sensitive tissues. Asymmetrical dimethylarginine (ADMA) is an endogenous inhibitor of NO synthase (NOS). We hypothesized that a reduction in endogenous ADMA would increase NO synthesis and thereby enhance insulin sensitivity.

Methods and Results—

To test this hypothesis we used a transgenic mouse in which we overexpressed human dimethylarginine dimethylaminohydrolase (DDAH-I). The DDAH-I mice had lower plasma ADMA at all ages (22 to 70 wk) by comparison to wild-type (WT) littermates. With a glucose challenge, WT mice showed a prompt increase in ADMA, whereas DDAH-I mice had a blunted response. Furthermore, DDAH-I mice had a blunted increase in plasma insulin and glucose levels after glucose challenge, with a 50% reduction in the insulin resistence index, consistent with enhanced sensitivity to insulin. In liver, we observed an increased Akt phosphorylation in the DDAH-I mice after i.p. glucose challenge. Incubation of skeletal muscle from WT mice ex vivo with ADMA (2 μmol/L) markedly suppressed insulin-induced glycogen synthesis in fast-twitch but not slow-twitch muscle.

Conclusions—

These findings suggest that the endogenous NOS inhibitor ADMA reduces insulin sensitivity, consistent with previous observations that NO plays a role in insulin sensitivity.
Targeting Connexin 43 Prevents Platelet-Derived Growth Factor-BB–Induced Phenotypic Change in Porcine Coronary Artery Smooth Muscle Cells
Authors: Chadjichristos Christos E. , Morel Sandrine , Derouette Jean-Paul , Sutter Esther , Roth Isabelle , Brisset Anne C. , Bochaton-Piallat Marie-Luce , Kwak Brenda R.
Published: February 2008

We previously reported that reducing the expression of the gap junction protein connexin (Cx)43 in mice restricts intimal thickening formation after acute vascular injury by limiting the inflammatory response and the proliferation and migration of smooth muscle cells (SMCs) toward the damaged site. SMC populations isolated from porcine coronary artery exhibit distinct phenotypes: spindle-shaped (S) and rhomboid (R). S-SMCs are predominant in the normal media, whereas R-SMCs are recovered in higher proportion from stent-induced intimal thickening, suggesting that they participate in the restenotic process. Here, we further investigate the relationship between connexin expression and SMC phenotypes using porcine coronary artery SMCs. Cx40 was highly expressed in normal media of porcine coronary artery in vivo, whereas Cx43 was barely detectable. In contrast, Cx40 was downregulated and Cx43 was markedly upregulated in stent-induced intimal thickening. In vitro, S-SMCs expressed Cx40 and Cx43. In R-SMCs, Cx43 expression was increased and Cx40 was absent. We confirmed that S-SMCs treated with platelet-derived growth factor-BB acquire an R phenotype. This was accompanied by an upregulation of Cx43 and a loss of Cx40. Importantly, platelet-derived growth factor-BB–induced S-to-R phenotypic change was prevented by a reduction of Cx43 expression with antisense, ie, S-SMCs retained their typical elongated appearance and the expression of α-smooth muscle actin, a well-known SMC differentiation marker, whereas the expression of S100A4, a typical marker of R-SMCs, was prevented. In conclusion, limiting Cx43 expression in S-SMCs prevents platelet-derived growth factor-BB–induced S-to-R modulation. This suggests that Cx43 may be an additional target for local delivery strategies aimed at reducing restenosis.
Milrinone for the Treatment of Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage
Authors: Fraticelli Amanda Tarabini , Cholley Bernard P. , Losser Marie-Reine , Saint Maurice Jean-Pierre , Payen Didier
Published: February 2008

Background and Purpose—

Attempts to reverse cerebral vasospasm (CVS) after aneurysmal subarachnoid hemorrhage (aSAH) rely on a limited number of treatments. Calcium channel blockers have proven a benefit but their vasodilating effect on spastic cerebral arteries is relatively modest. Milrinone, a phosphodiesterase inhibitor, combines vasodilating and inotropic properties, but limited data exist to support its use for the treatment of CVS. We assessed the efficacy and tolerance of milrinone in patients with CVS secondary to aSAH.

Methods—

Twenty-two consecutive patients with angiographically-proven CVS (arterial diameter reduction >40%) have been studied. Intraarterial milrinone was infused in the cerebral territory(ies) involved and followed by continuous intravenous infusion until Day 14 after initial bleeding. We evaluated angiographic reversal of CVS, hemodynamic tolerance, and neurological outcome 1 year after aSAH.

Results—

Thirty-four selective intraarterial infusions of milrinone were required to treat 72 vasospastic territories. Intraarterial milrinone resulted in 53±37% increase in arterial diameter (
P
<.0001). Milrinone infusion resulted in moderately increased heart rate, but systemic arterial pressure remained unchanged. Five patients (23%) had angiographically-proven vasospasm recurrence within 48 hours after the procedure. Two of them were successfully reversed after another intraarterial infusion of milrinone. The remaining 3 underwent mechanical angioplasty. Two patients (9%) died in ICU, and 2 were lost to follow-up. All other patients had very good neurological outcome (modified Rankin scale: 0.8±1.0; Barthel index: 100 [95–100]).

Conclusion—

This study suggests that milrinone is effective and safe for reversal of CVS after aSAH and should be tested in a large randomized trial.
Risk of Thromboembolic Events in Controlled Trials of rFVIIa in Spontaneous Intracerebral Hemorrhage
Authors: Diringer Michael N. , Skolnick Brett E. , Mayer Stephan A. , Steiner Thorsten , Davis Stephen M. , Brun Nikolai C. , Broderick Joseph P.
Published: February 2008

Background and Purpose—

Recombinant activated factor VII (rFVIIa) reduces hematoma expansion and improves outcome after intracerebral hemorrhage (ICH), with an apparent increase in nonfatal thromboembolic events (TEs) with higher doses. Despite low incidences of such events in rFVIIa-treated hemophiliacs, the frequency in older patients with more atherosclerosis and immobility has yet to be defined.

Methods—

Data were pooled from 3 randomized placebo-controlled studies in patients diagnosed within 3 hours of spontaneous ICH who received a single dose of rFVIIa (5 to 160 μg/kg; n=371) or placebo (n=115). Clinical/laboratory evaluations, lower extremity Doppler studies, and 72-hour CT scans were used to monitor for TEs. Adverse events occurring while hospitalized and serious events occurring through day 90 were carefully reviewed.

Results—

There was no overall increase in risk of total TEs in rFVIIa-treated patents; however, there were more arterial, but not venous, TEs in the high dose group (120 to 160 μg/kg) compared with placebo (5.4% versus 1.7%;
P
=0.13). Arterial events occurring within 7 days of drug administration classified as possibly or probably associated with study drug included myocardial ischemia (n=9, 8 were non–ST-segment elevation and non–Q-wave events; 2 of the 9 had sequelae) and ischemic stroke (n=9, 4 of which had likely causes other than rFVIIa). Regression analysis identified high doses (120 to 160 μg/kg) of rFVIIa as the only factor associated with arterial TEs (odds ratio=6.75;
P
=0.02).

Conclusions—

There appears to be a increased risk of arterial TEs associated with higher doses of rFVIIa in ICH patients as compared with placebo. Further studies are underway to identify specific factors associated with these events and to define the dose that maximizes benefit and minimizes risk.
Inflammatory and Injury Responses to Ischemic Stroke in Obese Mice
Authors: Terao Satoshi , Yilmaz Gokhan , Stokes Karen Y. , Ishikawa Mami , Kawase Takeshi , Granger D. Neil
Published: February 2008

Background and Purpose—

Although epidemiological studies reveal an increased incidence of obesity and an association between obesity and the prevalence/severity of ischemic stroke, little is known about the mechanisms that link obesity to ischemic stroke. This study tested the hypothesis that obesity exacerbates the cerebrovascular dysfunction and tissue injury induced by brain ischemia and reperfusion.

Methods—

The adhesion of leukocytes and platelets in cerebral venules, blood–brain barrier permeability, brain water content, and infarct volume were measured in wild-type, obese (
ob/ob
), and leptin-reconstituted
ob/ob
mice subjected to 30 minutes middle cerebral artery occlusion and reperfusion. Tissue and plasma cytokine levels were determined by cytometric bead array, and a role for monocyte chemoattractant protein-1 and interleukin-6 was assessed using blocking antibodies.

Results—

Compared with wild-type mice,
ob/ob
exhibited larger increases in leukocyte and platelet adhesion, blood–brain barrier permeability, water content, and infarct volume after middle cerebral artery occlusion–reperfusion. Reconstitution of leptin in
ob/ob
mice tended to further enhance all reperfusion-induced responses.
Ob/ob
mice also exhibited higher plasma levels of monocyte chemoattractant protein-1 and interleukin-6 than wild-type mice. Immunoneutralization of monocyte chemoattractant protein-1, but not interleukin-6, reduced infarct volume in
ob/ob
mice.

Conclusions—

Obesity worsens the inflammatory and injury responses to middle cerebral artery occlusion and reperfusion by a mechanism independent of leptin deficiency. monocyte chemoattractant protein-1 appears to contribute to the exaggerated responses to ischemic stroke in obese mice.
Effective and Safe Conditions of Low-Frequency Transcranial Ultrasonic Thrombolysis for Acute Ischemic Stroke
Authors: Saguchi Takayuki , Onoue Hisashi , Urashima Mitsuyoshi , Ishibashi Toshihiro , Abe Toshiaki , Furuhata Hiroshi
Published: February 2008

Background and Purpose—

Transcranial ultrasound (TUS) enhances thrombolysis and is expected to be useful for the treatment of ischemic stroke. However, neither its effectiveness in improving neurologic outcome nor its safety in living tissue has been fully established. We examined the efficacy and safety of low-frequency TUS under appropriate conditions of ultrasound for thrombolytic treatment in a rat middle cerebral artery stroke model.

Methods—

Sixty-five male Wistar rats were used. Rats with right middle cerebral artery stroke exhibiting left hemiparesis were blindly selected and randomly assigned to 1 of 3 groups: (1) control, no therapy; (2) tPA, intravenous administration of tissue plasminogen activator 3 hours after middle cerebral artery stroke, or (3) TUS, tPA administration and application of TUS (490 kHz, continuous wave, at an intensity of 0.8 W/cm
2
). Twenty-four hours after the onset of stroke, neurologic improvement was evaluated and brains were then removed. Thrombolysis at the origin of the right middle cerebral artery was examined. Thrombolysis ratio, cerebral infarct ratio, and rate of histologic evidence of hemorrhage were compared in the 3 groups.

Results—

Significantly better neurologic improvement (
P
=0.008), a higher thrombolysis ratio (
P
=0.041), and a reduction of cerebral infarct volume (
P
=0.047) were obtained in the TUS group compared with the tPA group, without an increase in hemorrhagic transformation.

Conclusions—

Our findings suggest that thrombolytic treatment with low-frequency TUS under appropriate conditions could be an effective and safe method of treatment for ischemic stroke.
Weight Loss After Stroke
Authors: Jönsson Ann-Cathrin , Lindgren Ingrid , Norrving Bo , Lindgren Arne
Published: February 2008

Background and Purpose—

Data on the prevalence and indicators of weight loss in population-based groups of stroke survivors are scarce. We aimed to find the predictors and indicators of weight loss >3 kg as a possible marker of malnutrition after stroke.

Methods—

We registered weight at baseline, after 4 months, and 1 year later in 305 survivors from a population-based cohort of first-ever stroke patients. Characteristics of the patients were registered at baseline and follow-ups, including glycosylated hemoglobin at baseline and follow-up II, eating difficulties at both follow-ups, and screening for depression at follow-up II. We used univariate and multivariate analyses to find baseline predictors and follow-up indicators related to weight loss >3 kg from baseline.

Results—

Among the 305 patients, 60% were male, the mean age was 72.5 years, and mean body mass index was 25.8 kg/m
2
. The main stroke types were cerebral infarction (89%), intracerebral hemorrhage (7%), and subarachnoid hemorrhage (4%). Weight loss >3 kg was found in 74 (24%) patients (mean, −6.6 kg) after 4 months and in 79 patients (26%; mean, −8.3 kg) 1 year later. Severe stroke and elevated glycosylated hemoglobin levels were baseline predictors of weight loss >3 kg. Indicators associated with short-term weight loss (at follow-up I) were eating difficulties, low prealbumin value, and dependence (Barthel Index), whereas indicators associated with long-term weight loss (follow-up II) were eating difficulties, hemorrhagic stroke, and low prealbumin value.

Conclusions—

Weight loss >3 kg after stroke indicates the need for closer observation regarding nutritional status. Monitoring of body weight may be useful, particularly among patients with severe stroke, eating difficulties, low prealbumin values, and impaired glucose metabolism.
Antidepressant Treatment and Worsening White Matter on Serial Cranial Magnetic Resonance Imaging in the Elderly
Authors: Steffens David C. , Chung Hyoju , Krishnan K. Ranga R. , Longstreth W.T. , Carlson Michelle , Burke Gregory L.
Published: February 2008

Background and Purpose—

In some studies, late life depression is associated with white matter lesions on MRI. The effect of different classes of antidepressants on progression of white matter lesions is unknown. Selective serotonergic reuptake inhibitors (SSRIs) may decrease platelet aggregation. We hypothesized that Cardiovascular Health Study participants taking SSRIs would less often have worsening white matter on serial MRI than participants not on antidepressants.

Methods—

Among 1826 participants who were not using an antidepressant at initial MRI scan, we examined the association of worsening in white matter grade from initial to follow-up MRI scans, 5 years apart on average, and antidepressant use between the scans. Logistic regression models were used, controlling for a variety of potential confounding variables.

Results—

Use of any antidepressant during the period of study was associated with worsening white matter. In a multivariable model, risk was slightly increased, not reduced, with use of serotonergic agents (OR 1.36, 95% CI 0.87 to 2.12) and was significantly increased with the use of tricyclic antidepressants (OR 1.77, 95% CI 1.07 to 2.94).

Conclusions—

The association between worsening white matter and use of tricyclic antidepressants was an unexpected finding that may relate to indications for use other than depression or to side effects such as hypotension. Protection against worsening was not seen with use of serotonergic agents.
Metabolic Syndrome and Its Components as Predictors of Ischemic Stroke in Type 2 Diabetic Patients
Authors: Protopsaltis Ioannis , Korantzopoulos Panagiotis , Milionis Haralampos J. , Koutsovasilis Anastasios , Nikolopoulos Georgios K. , Dimou Eftihia , Kokkoris Stelios , Brestas Paris , Elisaf Moses S. , Melidonis Andreas
Published: February 2008

Background and Purpose—

The available data regarding the association between metabolic syndrome (MS) or MS components and ischemic stroke in type 2 diabetics are limited and inconsistent. This study aimed to investigate these associations.

Methods—

Five hundred ninety-nine consecutive type 2 diabetic patients (mean age 60.4±9.6 years, 54% men) were followed-up for 10.1 years (median period). Baseline clinical and laboratory characteristics and the occurrence of a first-ever ischemic stroke during follow-up were recorded.

Results—

Seventy-eight patients developed a first-ever ischemic stroke. According to Cox proportional hazard model, waist circumference (hazard ratio, HR:1.006, 95% CI:1.002 to 1.010,
P
=0.003) and age (HR:1.061, 95% CI:1.002 to 1.125,
P
=0.04) were significant predictors. After incorporating various combinations of MS components in multivariate models, only age and waist circumference remained significant.

Conclusions—

MS per se at baseline or combinations of its components do not predict the development of ischemic stroke in type 2 diabetic patients. Waist circumference represents an independent prognostic factor and could be used as a clinical tool for stroke prevention in this population.
Ischemic Postconditioning Protects Against Global Cerebral Ischemia/Reperfusion-Induced Injury in Rats
Authors: Wang Jing-ye , Shen Jia , Gao Qin , Ye Zhi-guo , Yang Shui-you , Liang Hua-wei , Bruce Iain C. , Luo Ben-yan , Xia Qiang
Published: February 2008

Background and Purpose—

Ischemic postconditioning has been found to decrease brain infarct area and spinal cord ischemic injury. In this study, we tested the hypothesis that ischemic postconditioning reduces global cerebral ischemia/reperfusion-induced structural and functional injury in rats.

Methods—

Ten-minute global ischemia was induced by 4-vessel occlusion in male Sprague-Dawley rats. The animals underwent postconditioning consisting of 3 cycles of 15-second/15-second (Post-15/15), 30-second/30-second (Post-30/30), or 60-second/15-second (Post-60/15) reperfusion/reocclusion or 15-second/15-second reperfusion/reocclusion applied after a 45-second reperfusion (Post-45-15/15).

Results—

Ten minutes of ischemia and 7 days of reperfusion destroyed 85.8% of CA1 hippocampal neurons and 64.1% of parietal cortical neurons. Three cycles of Post-15/15, Post-30/30, and Post-45-15/15 reperfusion/reocclusion markedly reduced neuronal loss after 7 days or 3 weeks of reperfusion and diminished the deficiency in spatial learning and memory. After reperfusion, a period of hyperperfusion followed by hypoperfusion was observed, both of which were blocked by postconditioning. The cytosolic level of cytochrome
c
increased significantly after 48 hours of reperfusion, and this was inhibited by Post-15/15, Post-30/30, and Post-45-15/15. However, 3 cycles of 60-second/15-second reperfusion/reocclusion failed to protect against neuronal damage, behavioral deficit, or cytochrome
c
translocation.

Conclusions—

Our data provide the first evidence that an appropriate ischemic postconditioning strategy has neuroprotective effects against global cerebral ischemia/reperfusion injury and a consequent behavioral deficit and that these protective effects are associated with its ability to improve disturbed cerebral blood flow and prevent cytochrome
c
translocation.
Does Carotid Stent Cell Design Matter?
Authors: Schillinger Martin , Gschwendtner Manfred , Reimers Bernhard , Trenkler Johannes , Stockx Luc , Mair Johann , Macdonald Sumaira , Karnel Franz , Huber Kurt , Minar Erich
Published: February 2008

Background and Purpose—

Carotid stent cell design has recently been suggested to be a determinant of periprocedural and early postprocedural neurologic complications. We investigated the impact of closed- versus open-cell stent design on neurologic adverse events and mortality after carotid artery stenting.

Methods—

We studied 1684 consecutive patients (1010 asymptomatic, 674 symptomatic) from 10 European centers who underwent carotid artery stenting with either closed-cell (n=859, 51%) or open-cell (n=825, 49%) design stents. Rates of transient ischemic attack, stroke, and death on the day of the procedure (acute events) and from day 1 to day 30 after the procedure (subacute events) were analyzed (95% CIs).

Results—

Combined transient ischemic attack, stroke, or death rates, and stroke or death rates within 30 days of treatment were 6.1% (95% CI, 5.0 to 7.2) and 3.1% (95% CI, 2.3 to 3.9) for the closed-cell design versus 4.1% (95% CI, 3.2 to 5.0) and 2.4% (95% CI, 1.7 to 3.1) for the open-cell design stents (
P
=0.077,
P
=0.38), respectively, without significant differences in asymptomatic and symptomatic patients. By propensity-score–adjusted multivariable analysis, the open-cell carotid stent design was not associated with a differential risk for combined acute and subacute neurologic complications compared with closed-cell stents (adjusted odds ratio=0.84,
P
=0.53). When analyzed separately, the risk for acute events on the day of the procedure (adjusted odds ratio=0.83,
P
=0.57) and the risk for subacute events at days 1 to 30 (adjusted odds ratio=1.61,
P
=0.51) also were not significantly different between the groups.

Conclusions—

Current data do not support the superiority of a specific carotid stent cell design with respect to neurologic complications, stroke, and mortality risk.
A Scholar in the Company of Female Entertainers: Changing Notions of Integrity in Song to Ming Dynasty Painting
Authors: Blanchard Lara
Published: February 2008

The Ming dynasty painting Su Dongpo Returning to the Hanlin Academy represents an important departure from earlier images of prominent scholars, demonstrating how the visual tropes associated with integrity change over time. First, it depicts the eleventh-century official following his reinstatement in the capital, quite a change from Song and Yuan images of men of integrity retiring to the wilderness. Second, many female entertainers accompany him, a juxtaposition considered inappropriate for viewing in previous periods but increasingly popular in Ming painting. This paper proposes that by the mid-Ming dynasty, the figure of the female entertainer specifically connotes an urban setting, and, when paired with a scholar, suggests the high-minded and untrammeled qualities of the court or city hermit.
Words of Seduction, Lines of Resistance: Writing and Gender in Zheng Xi's Dream of Spring (1318)
Authors: de Pee Christian
Published: February 2008

This article contains a full, annotated translation of A Dream of Spring (Chunmeng lu), written in 1318 by Zheng Xi (1324 jinshi). In A Dream of Spring, Zheng Xi, despite being married, accepts a matchmaker's request to submit a poem to the family of Miss Wu. In the ensuing correspondence with Miss Wu, Zheng Xi uses his masculine literary prerogative to compromise her chastity, which she struggles to defend by the more stringent conventions of feminine composition. The analysis of this fourteenth-century story supplements studies of gendered subjects in the literature of the late Ming and Qing dynasties.
Reconstructing Religions: Jewish place and space in the Jerusalem YMCA Building, 1919-1933
Authors: Gitler Inbal Ben-Asher
Published: February 2008

This paper discusses the representation of Jewish religion and culture in the architecture of the YMCA Building in Jerusalem, a prominent edifice built by the New York architect Arthur Loomis Harmon for the American YMCA. Within it, Jewish place and space were reconstructed as part of an architecture planned to promote Jewish, Christian and Moslem co-existence through an American secular cultural curriculum and a Christian vision of peace.
Distribución sociométrica en las aulas de chicos y chicas a lo largo de la escolaridad
Authors: García-Bacete Francisco-Juan , Sureda Inmaculada , Monjas Inés
Published: February 2008

La muestra está formada por 2173 alumnos escolarizados (45.7% eran chicas y el 54.3% chicos) en 92 aulas de todos los cursos desde el segundo ciclo de infantil al primer ciclo de secundaria, de 24 colegios públicos de Castellón, Valladolid y Palma de Mallorca.

Chicos y chicas son sociométricamente diferentes en todos los ciclos. Ellos son más rechazados y controvertidos y ellas más ignoradas y promedio. Sólo la proporción entre chicos-controvertidos y chicas-controvertidas varía en la escolaridad. La distribución sociométrica de los chicos es estable durante toda la escolaridad, la de las chica cambia (menos preferidas al principio y final de la escolaridad y más controvertidas en secundaria). El rechazo está asociado al género masculino. Hay variaciones en la distribución sociométrica de un aula a otra.
Evidencias a favor de la disrupción de la estrategia en el olvido de información estereotípica
Authors: Iglesias-Parro Sergio , Arias Ana V. , Ortega Almudena
Published: February 2008

Se realizaron dos experimentos que pretendían cubrir dos objetivos principales. En primer lugar, replicar los efectos de olvido que previamente se habían encontrado en el paradigma de señalización de una parte del total (SPT) utilizando atributos de personalidad—estereotípica y personal—. En segundo lugar, se pretendía identificar el mecanismo subyacente a los efectos de olvido encontrados en el paradigma de la SPT. Para ello, se contrastaron las hipótesis y predicciones inhibitorias frente a las hipótesis basadas en la interferencia. Los resultados respecto al primer objetivo, replican los efectos clásicos del paradigma SPT con información estereotípica. Respecto al segundo objetivo, frente a explicaciones inhibitorias, se encontraron evidencias de que el olvido de información, como consecuencia de la presentación de claves de recuerdo, estaría explicado por la hipótesis de la disrupción de la estrategia. Las repercusiones de los resultados obtenidos se discuten por un lado, en el marco del análisis de los procesos de memoria y por otro, en el de los mecanismos que subyacen al mantenimiento y cambio de los estereotipos.
Sobre la resistencia a la Psicología Social
Authors: Briñol Pablo , Blanco Amalio , de la Corte Luis
Published: February 2008

La Psicología Social no se ha traducido en un progreso sustantivo del bienestar y las relaciones humanas, ni tampoco parece haber contribuido a producir los cambios sociales y políticos que se podría esperar de una disciplina dedicada al estudio científico de la conducta social humana. En el presente trabajo se analizan algunas de las barreras con las que se encuentran los psicólogos sociales (entendidos como emisores persuasivos) para transmitir sus conocimientos (la Psicología Social como mensaje persuasivo) a distintos receptores (vistos como agentes activos en la búsqueda, recepción, procesamiento y aceptación de información). Una vez examinados algunos de estos obstáculos y resistencias desde el marco del cambio de actitudes, se sugieren algunas recomendaciones prácticas para comunicar influyendo de forma mas efectiva.
Los turistas nos visitan, los inmigrantes nos invaden. Un estudio de la percepción de amenaza desde el concepto de grupalidad percibida
Authors: Rodríguez Armando , Betancor Verónica , Delgado Naira , Rodríguez Ramón , Pacios Alberto
Published: February 2008

El concepto de entidad o grupalidad percibida, grado en que percibimos a un conjunto de personas como un grupo compacto, explica muchos aspectos diferenciales de la percepción grupal. Sin embargo, la relación entre entidad y amenaza percibida ha recibido escasa consideración. En esta investigación queremos comprobamos si los grupos que se categorizan como una entidad se perciben más amenazantes que los que se categorizan como un agregado de individuos. Para ello, los participantes respondían a un cuestionario en el que se medía tanto la percepción de grupalidad como la percepción de amenaza, de seis categorías sociales y tres agregados. Como se preveía, los resultados muestran que los grupos con más entidad se perciben más amenazantes que los de menos entidad. Los resultados señalan la utilidad del concepto de entidad para entender la percepción diferencial de amenaza de diferentes grupos sociales.