bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk Factor, Pattern, Etiology and Outcome in Ischemic Stroke Patients with Cancer: A Nested Case-Control Study
Authors: Zhang Yun Yun , Cordato Dennis , Shen Qing , Sheng Ai Zhen , Hung Wai Tak , Chan Daniel K.Y.
Published: December 2006

Background: Coagulation disorders are seen in cancer patients, but it is not clear whether cancer predisposes stroke patients to unique characteristics. The aim of the study was to investigate risk factors, pattern,etiology and outcome in stroke patients with cancer. Methods: A retrospective review of all ischemic stroke (IS) patients with cancer (n = 56) admitted to Bankstown-Lidcombe Hospital, Sydney, Australia, between January 1999 and December 2004 was conducted and comparison made to age- and gender-matched noncancer IS patients admitted to the same hospital during the same period. Results: Vascular risk factors and stroke pattern were comparable in cancer and noncancer groups. Poststroke thrombotic episodes (myocardial infarction, deep vein thrombosis or pulmonary emboli) were more common in the cancer group than in the noncancer group (11 vs. 0%, p = 0.031). Depression was also more common in the cancer group than in the noncancer group (14 vs. 2%, p = 0.039). There was a tendency for more patients in the cancer group to die in hospital (30 vs. 14%, p = 0.078). Conclusions: Coagulation disorders were more likely to be seen in stroke cancer patients, and patients with cancer tended to have a higher in-hospital poststroke mortality. Larger sample size studies may identify further differences in the characteristics of stroke patients with cancer.
Lp(a) Lipoprotein and Plasminogen Activity in Patients with Different Etiology of Ischemic Stroke
Authors: Petersen Nils H. , Schmied Alexander B. , Zeller Jörn A. , Plendl Hansjörg , Deuschl Günther , Zunker Peter
Published: December 2006

Background and Purpose: Lp(a) lipoprotein plays an important part in atherothrombogenesis and is considered an independent risk factor for coronary heart disease. However, its role in cerebrovascular disease remains unclear, in particular because of the heterogeneous nature of strokes. We investigated whether elevated Lp(a) is more frequent in ischemic stroke related to atherothrombosis than in other etiologies of stroke. Because of the close structural homology between Lp(a) and plasminogen, we also studied the role of plasminogen in different stroke subtypes and whether there is a dependency on Lp(a) plasma levels. Methods: Lp(a) levels and plasminogen activity were measured in 253 consecutive patients with acute ischemic stroke and in 63 controls (CS). Subtypes of stroke were established according to the TOAST criteria. Results: Median Lp(a) levels were found to be higher in the total cerebral infarction group and in patients with large artery atherosclerosis (LAA) when compared with CS (20.9 and 22.0 mg/dl, respectively, vs. 16.0 mg/dl; p < 0.05). In addition, elevated Lp(a) levels >30 mg/dl were more frequent among the LAA subgroup than among CS (39.4 vs. 11.1%; p < 0.001). Mean plasminogen activity was lower in the total cerebral infarction group (110.8 vs. 120.3%; p < 0.001) and in patients with cardioembolic stroke (109.8 vs. 120.3%; p < 0.05) when compared with CS. There was no correlation between Lp(a) levels and plasminogen activity. Conclusions: Our results support the hypothesis that elevated Lp(a) is a risk factor for ischemic stroke and especially for strokes caused by LAA. Low plasminogen activity may play a role in the pathogenesis of cerebrovascular disease, especially for the development of cardioembolic stroke.
Specialized Stroke Services: A Meta-Analysis Comparing Three Models of Care
Authors: Foley Norine , Salter Katherine , Teasell Robert
Published: December 2006

Background: Using previously published data, the purpose of this study was to identify and discriminate between three different forms of inpatient stroke care based on timing and duration of treatment and to compare the results of clinically important outcomes. Methods: Randomized controlled trials, including a recent review of inpatient stroke unit/rehabilitation care, were identified and grouped into three models of care as follows: (a) acute stroke unit care (patients admitted within 36 h of stroke onset and remaining for up to 2 weeks; n = 5), (b) units combining acute and rehabilitative care (combined; n = 4), and (c) rehabilitation units where patients were transferred onto the service approximately 2 weeks following stroke (postacute; n = 5). Pooled analyses for the outcomes of mortality, combined death and dependency and length of hospital stay were calculated for each model of care, compared to conventional care. Results: All three models of care were associated with significant reductions in the odds of combined death and dependency; however, acute stroke units were not associated with significant reductions in mortality when this outcome was analyzed separately (OR 0.80; 95% CI: 0.61–1.03). Postacute stroke units were associated with the greatest reduction in the odds of mortality (OR 0.60; 95% CI: 0.44–0.81). Significant reductions in length of hospital stay were associated with combined stroke units only (weighted mean difference –14 days; 95% CI: –27 to –2). Conclusions: Overall, specialized stroke services were associated with significant reductions in mortality, death and dependency and length of hospital stay although not every model of care was associated with equal benefit.
Executive Function Is Independently Associated with Performances of Balance and Mobility in Community-Dwelling Older Adults after Mild Stroke: Implications for Falls Prevention
Authors: Liu-Ambrose Teresa , Pang Marco Y.C. , Eng Janice J.
Published: December 2006

Background: Stroke survivors have a high incidence of falls. Impaired executive-controlled processes are frequent in stroke survivors and are associated with falls in this population. Better understanding of the independent association between executive-controlled processes and physiological fall risk (i.e. performances of balance and mobility) could enhance future interventions that aim to prevent falls and to promote an independent lifestyle among stroke survivors. Methods: Cross-sectional analysis of 63 adults who suffered a mild stroke >1 year prior to the study, aged ≧50 years. Results: Cognitive flexibility was independently associated with performances of balance and mobility in community-dwelling older adults after mild stroke, after accounting for age, quadriceps strength of the paretic side and current physical activity level. Conclusions: Clinicians may need to consider cognitive function when assessing and treating impaired balance and mobility in community-dwelling older adults after mild stroke.
Barriers to Stroke Thrombolysis in a Geographically Defined Population
Authors: Engelter S.T. , Gostynski M. , Papa S. , Ajdacic-Gross V. , Lyrer P.A.
Published: December 2006

Objective: Barriers to thrombolysis are rather assessed for hospitalized stroke patients than among geographically defined populations. In a population-based approach, we assessed (1) the utilization rate of stroke thrombolysis in the community, and (2) the significance of the chosen stroke care provider as a potential barrier to thrombolysis. Methods: We performed a databank-based post hoc analysis, derived from data ascertained in a prospective, population-based stroke study among the permanent residents of the canton Basel-City, Switzerland. For the cohort with an onset assessment interval (OAI) ≤3 h, we compared thrombolyzed with nonthrombolyzed patients concerning demographic variables, the National Institutes of Health stroke scale (NIHSS) score, OAI, risk factors, and the type of stroke care provider. For patients without thrombolysis despite an OAI ≤3 h, barriers to thrombolysis were compiled. Results: Among 269 patients, 49 had an OAI ≤3 h (18% of all patients and 38% of those 128 patients with exactly known time of onset). Fourteen patients received thrombolysis, amounting to a utilization rate of 5.2% (95% CI 2.9–8.6) for all patients and 29% (95% CI 17–43) for the OAI ≤3-hour cohort. For the latter, thrombolyzed differed from nonthrombolyzed patients in higher NIHSS score and type of stroke care provider, but not in demographic variables, OAI, or risk factors. Fourteen of 40 patients (35%) primarily admitted to the stroke unit received thrombolysis, compared with none of 9 patients primarily treated elsewhere (p < 0.04). In the OAI ≤3-hour cohort, mild or regressing stroke severity (48%), admission to hospitals not offering thrombolysis (20%), computed tomography or laboratory contraindications (17%) and severe comorbidity (14%) were barriers to thrombolysis. Conclusion: In this geographically defined population, every 20th stroke patient received thrombolysis. Only a minority of patients had an OAI ≤3 h, rendering late admission the most common barrier to thrombolysis. In the OAI ≤3-hour cohort, admission to hospitals not offering thrombolysis prompted exclusion from thrombolysis as often as established contraindications. Thus, acute stroke patients should solely be brought to hospitals providing thrombolysis.
Long-Term Mortality, Morbidity and Hospital Care following Intracerebral Hemorrhage: An 11-Year Cohort Study
Authors: McGuire Alistair J. , Raikou Maria , Whittle Ian , Christensen Michael C.
Published: December 2006

Background and Purpose: Intracerebral hemorrhage (ICH) represents the severest form of stroke, yet examinations of long-term prognosis and associated health care use are rare. This study assessed survival, morbidity and cost of hospital care over 11 years following a first-ever ICH in the UK. Methods: We used a population-based retrospective inception cohort design using data from the Hospital Record Linkage System in Scotland. Long-term survival, morbidity and treatment provided in hospitals were evaluated in all patients with a first diagnosis of ICH in 1995. A cohort of ischemic stroke (IS) patients was also examined for comparison. Results: A total of 705 patients with ICH and 8,893 with IS were identified. The mean age was 65 years (SD = 17.2) for ICH and 73 years (SD = 11.8) for IS at stroke onset. The acute in-hospital mortality was 45.7 and 30.1% for ICH and IS, 51.2 and 39.9% at 1 year, while 76.0 and 80.4% were dead 11 years later. The cumulative risk of nonfatal or fatal ICH was 8.0, 12.7 and 13.7% at 1, 5 and 10 years, and 7.0, 11.1 and 12.9% for IS in the ICH cohort. The mean cost of initial hospital care was GBP 10,332 (SD = 19,919) for ICH and GBP 9,937 (SD = 15,777) for IS. The mean total costs over 11 years were GBP 18,629 (SD = 29,943) for ICH and GBP 21,505 (SD = 27,190) for IS. Conclusion: Following a first ICH, individuals have a poorer short-term prognosis than individuals with IS, yet both ICH and IS imply significant follow-up care.
Glutathione-S-Transferase Pi Expression in Toxic Epidermal Necrolysis: A Marker of Putative Oxidative Stress in Keratinocytes
Authors: Paquet P. , Piérard G.E.
Published: December 2006

Background: Toxic epidermal necrolysis (TEN) is a dramatic drug-induced emergency related to extensive destruction of the epidermis. There is evidence that its pathomechanism involves impaired detoxication of xenobiotics. Glutathione-S-transferase π (GST-π) is a phase II detoxifying enzyme involved in drug metabolization by human keratinocytes. Method: Immunohistochemistry was performed in order to assess the expression of GST-π in keratinocytes of TEN, other cutaneous adverse drug reactions and bullous pemphigoid. Results: GST-π was disclosed in the involved epidermis of 16/16 TEN patients. It was present in the cytoplasm of suprabasal keratinocytes. GST-π was also expressed in the clinically uninvolved skin in a majority (8/12) of TEN patients. By contrast, it was rarely and poorly expressed in the other tested dermatoses. Conclusion: The pathomechanism of TEN is not related to an impaired quantitative expression of GST-π. GST-π expression is an early event in TEN. As oxidative stress is a major inducer of GST-π, this mechanism might be involved in TEN. Its GST-π expression mainly restricted to the suprabasal keratinocytes suggests that the pathomechanisms leading to keratinocyte death in TEN are distinct at different levels of the epidermis.
Antiseptic Efficacy of a Low-Dosed Topical Triclosan/Chlorhexidine Combination Therapy in Atopic Dermatitis
Authors: Wohlrab J. , Jost G. , Abeck D.
Published: December 2006

The topical application of triclosan as an antistaphylogenic antiseptic has proven beneficial in atopic dermatitis. Especially in lipophilic carriers, triclosan is applied in a concentration range between 1 and 5%, usually 2%. However, as a phenol, triclosan is not undisputed and may result in local exacerbation of the disease by eliciting irritative secondary reactions, especially in high concentrations. Chlorhexidine is also an antiseptic which is very effective against Staphylococciand nearly equivalent to triclosan with respect to its antistaphylogenic efficacy. In light of this, the combination of the two active substances in very low concentrations offers a possible option of using the additive effects of the two substances to minimize the risk of side effects. In a uniform W/O emulsion carrier alternatively containing 0.3% triclosan combined with 0.34% chlorhexidine dihydrochloride or 2.0% triclosan, the antibacterial efficacy against Gram-positive skin bacteria could be proven in a preclinical comparison with a reference preparation containing fusidic acid. Subsequently, the pathogen-reducing effect was examined in a clinical study of the influence on clinical severity in patients with atopic dermatitis. Both investigation methods showed that the two test preparations were slightly inferior to the reference preparation, but result in the same degree of pathogen reduction and improvement in the severity of existing atopic dermatitis in direct comparison. The overall results support the conclusion that a combination of triclosan and chlorhexidine in low concentrations as well as the existing antiseptic standard of a 2% triclosan preparation are suitable for pathogen reduction and thus for improving atopic dermatitis.
Influence of Different Anesthetics on Skin Oxygenation Studied by Electron Paramagnetic Resonance in vivo
Authors: Abramovic Z. , Sentjurc M. , Kristl J. , Khan N. , Hou H. , Swartz H.M.
Published: December 2006

The effects of two general anesthetics on skin oxygenation in mice are evaluated by electron paramagnetic resonance oximetry. Up to now no data on the effects of different anesthetics on skin oxygenation could be found. In this study animals were anesthetized with ketamine/xylazine or isoflurane, and partial pressure of oxygen (pO2) in the skin, heart rate and hemoglobin oxygen saturation were followed as a function of time and inhaled oxygen concentration. The skin pO2 significantly increased continuously for about 60 min in mice anesthetized with isoflurane and remained constant after that. During ketamine/xylazine anesthesia, the pO2 in the skin only slightly decreased. The skin pO2 increased with higher inspired oxygen concentrations for both anesthetics groups. When breathing 21% oxygen, mice anesthetized with isoflurane had two-fold higher pO2 in the skin compared to mice anesthetized with ketamine/xylazine. The heart rate was significantly lower in animals anesthetized with ketamine/xylazine, while hemoglobin saturation was almost the same in both groups at all inhaled oxygen concentrations. These results show that the type of anesthesia is an important parameter that needs to be considered in experiments where skin pO2 is followed.
Elastin Expression in a Newly Developed Full-Thickness Skin Equivalent
Authors: Mewes K.R. , Raus M. , Bernd A. , Zöller N.N. , Sättler A. , Graf R.
Published: December 2006

The resilience of the human skin is mediated by elastic fibres mainly consisting of fibrillins and elastin. In order to establish a model system to study the impact of cosmetic and pharmaceutical compounds on the elastic system in vitro, we analyzed the expression of elastin in a newly developed full-thickness skin model. After a 5-week cultivation period the skin model developed a fully differentiated epidermis including a stratum corneum. The dermis contains fibroblasts embedded in extracellular matrix proteins. The models were viable until at least 51 days at the air-liquid interface (ALI) culture. Using immunohistochemistry we detected elastin first on day 7 of ALI. With proceeding culture time, elastin-positive fibres of different lengths and distribution patterns accumulated in the dermal compartment. Elastin mRNA expression started on day 7 of ALI, increased until day 10 and then dropped to a level comparable to that of day 7. Our results demonstrate that in our full-thickness skin model an in vivo-like elastic system, which clearly mimics at least two subsets of dermal elastic fibres, is generated. This physiological property favours the model as a promising animal-free approach to study those processes leading to an environment- and age-dependent decrease in skin elasticity.
Healing Impairment Effect of Cyclooxygenase Inhibitors on Dextran Sulfate Sodium-Induced Colitis in Rats
Authors: Tsubouchi Ryoichi , Hayashi Shusaku , Aoi Yoko , Nishio Hikaru , Terashima Shun , Kato Shinichi , Takeuchi Koji
Published: December 2006

We examined the effects of various cyclooxygenase (COX) inhibitors on the healing of colonic lesions induced by dextran sulfate sodium (DSS) in the rat. Colonic lesions were induced by 2.5% DSS in the drinking water for 7 days, and then the animals were fed with tap water for subsequent 7 days. Indomethacin (a nonselective COX inhibitor), SC-560 (a selective COX-1 inhibitor), or rofecoxib (a selective COX-2 inhibitor) was given orally twice daily after termination of the DSS treatment. DSS treatment caused severe colonic lesions with a decrease in body weight gain and colon length as well as an increase in myeloperoxidase activity and thiobarbituric acid reactant levels. The severity of colitis gradually reduced, with an improvement of morphological and histological alterations. Daily administration of indomethacin and rofecoxib significantly delayed the healing of colitis with deleterious influences on histological restitution as well as mucosal inflammation, while SC-560 had no effect. Although COX-1 mRNA was expressed in the colon without much alteration during the test period, the expression of COX-2 was upregulated with a peak on day 3 and decreased thereafter. The mucosal prostaglandin E2 content in the colon showed a biphasic change, in parallel with that of the COX-2 expression. The increased prostaglandin E2 production in the injured mucosa was attenuated by indomethacin and rofecoxib, but not by SC-560. These results suggest that endogenous prostaglandins produced by COX-2 play an important role in the healing of DSS-induced colonic lesions. Caution should be paid to the use of selective COX-2 inhibitors as well as nonsteroidal anti-inflammatory drugs in patients with colitis.
Incidence and Predictors of Development of Acute Renal Failure Related to Treatment of Congestive Heart Failure with ACE Inhibitors
Authors: Cruz Constança S. , Cruz Luzia S. , Silva Giulliana R. , Marcílio de Souza Carlos A.
Published: December 2006

Background/Aims: Recent studies have shown high rates of morbimortality associated with hyperkalemia in congestive heart failure (CHF) patients treated with angiotensin-converting enzyme inhibitors (ACEI) plus spironolactone and the best predictor of this electrolytic disorder was a decrease in renal function. We aim to identify the incidence and predictors of acute renal failure (ARF) related to treatment with ACEI associated or not with spironolactone. Methods: We conducted a cohort study and followed 114 consecutive cases of CHF patients treated with ACEI at admission to a University Hospital. We performed measurements of serum creatinine and potassium levels three times a week, and systolic and diastolic blood pressures every 8 h, daily. Results: Among 114 patients, 25% developed ARF, 15% hyperkalemia and 3% severe hyperkalemia. Predictors of ARF were a decrease in average blood pressure 25 mm Hg (OR 18.2; 95% CI: 6.2, 53.5); class IV CHF (OR 4.7; 95% CI: 1.7, 12.7), diabetes (OR 2.6; 95% CI: 1.1, 6.4) and hypertension (OR 3.0; 95% CI: 1.2, 7.4). Conclusions: ARF and hyperkalemia are common complications in CHF patients after treatment with ACEI. Diabetic, hypertensive and class IV CHF patients who experienced a decrease in average blood pressure 25 mm Hg were more susceptible to ARF.
Fatal Bleeding following Delivery: A Manifestation of the Vascular Type of Ehlers-Danlos’ Syndrome
Authors: Björck M. , Pigg M. , Kragsterman B. , Bergqvist D.
Published: December 2006

Introduction: The vascular form of Ehlers-Danlos’ syndrome (type IV) is a potentially lethal genetic condition because of rupture of major arteries, often in the peri-partum period. Case Report: We report a 31-year-old primipara who died from a rupture of the right subclavian artery. The patient had several symptoms and signs typical of the disease. The rupture occurred during the expulsion-phase of delivery but was recognized only on day 9. Conclusion: Early recognition is crucial to avoid maternal mortality due to this genetic disorder. Once the condition is suspected, the clinical diagnosis is straightforward.
Fetal Intravenous Immunoglobulin Therapy in Rhesus Hemolytic Disease
Authors: Kriplani Alka , Malhotra Singh Bhawna , Mandal Kavita
Published: December 2006

Intrauterine blood transfusion is the mainstay of treatment of fetal rhesus hemolytic anemia with optimal perinatal outcome. Postnatal immunoglobulin therapy has been successfully used in the management of alloimmunized neonates and has shown to decrease the need for exchange transfusion. We report the first case series of fetal immunoglobulin therapy in the antenatal management of severe Rh incompatibility.
A Systematic Review of the Psychological Risk Factors Associated with Near Fatal Asthma or Fatal Asthma
Authors: Alvarez G.G. , FitzGerald J.M.
Published: December 2006

Psychological factors such as anxiety, depressive disorders and/or personality disorders may predispose patients with asthma to near fatal asthma (NFA) or fatal asthma (FA). NFA is defined by an asthma exacerbation resulting in respiratory arrest requiring mechanical ventilation or a pCO2 ≧45 mm Hg. Most studies have used the case-control study design. Several studies analyzing the effects of psychological factors on the risk of NFA or FA have shown conflicting results. We reviewed all of the literature found by the systematic search done of psychological factors on the risk NFA or FA. A MEDLINE search identified 423 articles between 1960 and March 2006. Seven case-controlled studies were identified following strict applications of the inclusion and exclusion criteria. Due to the significant heterogeneity in the measurement of the psychological factors, a summary statistic was not calculated. The trial characteristics were tabulated and qualitative trends were observed to explain the heterogeneity in the results of the studies. Recommendations on future studies in the field are outlined in detail. Following a systematic assessment of all published studies, we cannot conclude that psychological factors increase the risk of NFA and FA.
Effect of Corticosteroids on Hemostasis and Pulmonary Arterial Pressure during Chronic Obstructive Pulmonary Disease Exacerbation
Authors: Kunter Erdogan , Ilvan Ahmet , Ozmen Namik , Demirer Ersin , Ozturk Ahmet , Avsar Kadir , Sayan Ozkan , Kartaloğlu Zafer
Published: December 2006

Background: Hemodynamic and hemostatic abnormalities are reportedly frequent in chronic obstructive pulmonary disease (COPD). Objectives: We investigated the changes in systolic pulmonary artery pressure (PAPs) and hemostatic status and the effects of systemic steroid treatment (SST) during COPD exacerbation. Methods: Consecutive 26 male and 4 female patients as well as 10 controls were enrolled. The nonsteroid treatment (NST) group received standard treatment without steroids, and the other group received additional SST. Initial values of blood gases, spirometry and PAPs, P-selectin, D-dimer and fibrinogen levels, activities of thrombocyte aggregation, antithrombin III (AT III), protein C (PC), protein S, activated PC resistance (APCR), prothrombin time and partial thromboplastin time were obtained and compared with values at day 10. Results: Improvement in spirometry and blood gases was more prominent with SST. At presentation, patients had higher PAPs, P-selectin, D-dimer and fibrinogen but lower AT III levels than controls. PAPs and fibrinogen levels significantly decreased in the SST group while P-selectin levels further increased in the NST group. The D-dimer level significantly decreased in both groups. Means of AT III, PC and protein S increased in the SST and decreased in the NST group, but only the decrease in PC in the NST group was meaningful. Compared with the controls, AT III levels in the NST group and activated PC resistance in the SST group were significantly decreased. Thrombocyte aggregation tests suggested an incline after 10 days in both groups. Conclusions: We suggest that in patients with COPD exacerbation, addition of systemic corticosteroids to treatment results in better outcome in normalization of PAPs, hemostasis, pulmonary functions and blood gases.
Implications of Early Structural-Functional Changes in the Endothelium for Vascular Disease
Authors: Simionescu Maya
Published: December 2006

By location, between the blood and tissues and the multiple functions, the endothelial cells (ECs) play a major role in securing body homeostasis. The ECs sense all variations occurring in the plasma and interstitial fluid, and respond (function of intensity), initially by modulation of their constitutive functions, then by dysfunction, expressed by temporarily altered functions and a phenotypic shift, and ultimately by injury/death. In dyslipidemia/hyperglycemia, the initial response of EC is the modulation of 2 constitutive functions: permeability and biosynthesis. Increased transcytosis of plasma β-lipoproteins leads to their accumulation within the hyperplasic basal lamina, interaction with matrix proteins, and conversion to modified and reassembled lipoproteins (MRL). This generates a multipart inflammatory process and EC dysfunction characterized by expression of new cell adhesion molecules and MCP-1 that trigger T-lymphocytes and monocyte recruitment, diapedesis, and homing within the subendothelium where activated macrophages become foam cells. The latter, together with the subendothelial accrual of MRL, growth factors, cytokines, and chemokines, and accretion of smooth muscle cells of various sources lead to atheroma formation; in advanced disease, the EC overlaying atheroma take up lipids, become EC-derived foam cells, and the cytotoxic ambient ultimately conducts to EC apoptosis. Understanding the mechanisms of EC dysfunction is a prerequisite for EC-targeted therapy to reduce the incidence of cardiovascular diseases.
Cerebrovascular Nitrosative Stress Mediates Neurovascular and Endothelial Dysfunction Induced by Angiotensin II
Authors: Girouard Helene , Park Laibaik , Anrather Josef , Zhou Ping , Iadecola Costantino
Published: December 2006

Objective—Angiotensin II (AngII) disrupts the regulation of the cerebral circulation through superoxide, a reactive oxygen species (ROS) generated by a nox2-containing NADPH oxidase. We tested the hypothesis that AngII-derived superoxide reacts with nitric oxide (NO) to form peroxynitrite, which, in turn, contributes to the vascular dysfunction.

Methods and Results—Cerebral blood flow (CBF) was monitored by laser Doppler flowmetry in the neocortex of anesthetized mice equipped with a cranial window. AngII (0.25±0.02 μg/kg/min; intravenous for 30 to 45 minutes) attenuated the cerebral blood flow (CBF) increase produced by topical application of the endothelium-dependent vasodilator acetylcholine (−43±1%) and by whisker stimulation (−47±1%). AngII also increased the nitration marker 3-nitrotyrosine (3-NT) in cerebral blood vessels, an effect dependent on NO and nox2-derived ROS. Both the cerebrovascular effects of AngII and the nitration were attenuated by pharmacological inhibition or genetic inactivation of NO synthase. The nitration inhibitor uric acid or the peroxynitrite decomposition catalyst FeTPPS abolished AngII-induced cerebrovascular nitration and prevented the cerebrovascular effects of AngII.

Conclusions—These findings provide evidence that peroxynitrite, formed from NO and nox2-derived superoxide, contributes to the deleterious cerebrovascular effects of AngII. Inhibitors of peroxynitrite action may be valuable tools to counteract the deleterious cerebrovascular effects of AngII-induced hypertension.
Platelet Activity, Coagulation, and Fibrinolysis During Exercise in Healthy Males
Authors: Li Nailin , He Shu , Blombäck Margareta , Hjemdahl Paul
Published: December 2006

Background—

Relationships between exercise-induced activation of platelets, blood coagulation, and fibrinolysis, and the importance of thrombin for responses to exercise are not clear.

Methods and Results—

Effects of thrombin inhibition on hemostatic parameters were examined in a double-blind crossover study comparing the direct thrombin inhibitor argatroban (350 μg/kg intravenous bolus followed by 25 μg/kg per minute of infusion), the indirect thrombin inhibitor enoxaparin (0.75 mg/kg, intravenous bolus), or placebo (saline) in 21 healthy males. Measurements were made at rest, before and during/after thrombin inhibitor treatment, and immediately after exhaustive exercise. At rest argatroban abolished, and enoxaparin attenuated platelet activation by thrombin, but not by adenosine diphosphate. Argatroban and, even more so, enoxaparin decreased thrombin generation (prothrombin F1+2) and the coagulation potential, and increased the fibrinolytic potential. Exercise increased circulating activated platelets (from 5.5±0.3 to 9.4±0.9×10
9
/L;
P
<0.001), circulating platelet–platelet microaggregates, the platelet responsiveness to in vitro stimulation, leukocyte activation (leukocyte CD11b expression and plasma elastase), and platelet–leukocyte aggregation (
P
<0.01 for all). Exercise increased coagulation (F1+2;
P
<0.01) and fibrinolysis, but did not alter the balance between them; fibrin gel permeability increased (
P
<0.01), probably because of release of endogenous tissue plasminogen activator from the vessel wall. Neither argatroban nor enoxaparin counteracted exercise-induced platelet or leukocyte activation. Both thrombin inhibitors augmented exercise effects on fibrinolysis.

Conclusions—

Strenuous exercise enhances platelet and leukocyte activation independently of thrombin. Exercise augments both coagulation and fibrinolysis, but the balance between them appears to be maintained. At therapeutic dosages argatroban counteracted thrombin-induced platelet activation most efficiently, whereas enoxaparin had somewhat stronger anticoagulant and profibrinolytic effects.
In Vivo Plaque Characterization Using Intravascular Ultrasound–Virtual Histology in a Porcine Model of Complex Coronary Lesions
Authors: Granada Juan F. , Wallace-Bradley David , Win Htut K. , Alviar Carlos L. , Builes Angela , Lev Eli I. , Barrios Roberto , Schulz Daryl G. , Raizner Albert E. , Kaluza Greg L.
Published: December 2006

Objective—

To determine the accuracy of detection of different tissue types of intravascular ultrasound–virtual histology (IVUS-VH) in a porcine model of complex coronary lesions.

Methods and Results—

Coronary lesions were induced by injecting liposomes containing human oxidized low-density lipoprotein into the adventitia of the arteries. IVUS-VH imaging was performed in vivo at 8.2±1.6 weeks after injection. A total of 60 vascular lesions were analyzed and compared with their correspondent IVUS-VH images. Correlation analysis was performed using linear regression models. Compared with histology, IVUS-VH correctly identified the presence of fibrous, fibro-fatty, and necrotic tissue in 58.33%, 38.33%, and 38.33% of lesions, respectively. The sensitivity of IVUS-VH for the detection of fibrous, fibro-fatty, and necrotic core tissue was 76.1%, 46%, and 41.1% respectively. A linear regression analysis performed for each individual plaque component did not show strong correlation that would allow significant prediction of individual values.

Conclusions—

In a porcine model of complex coronary lesions, IVUS-VH was not accurate in detecting the relative amount of specific plaque components within each individual corresponding histological specimen.
Apolipoprotein E3- and Nitric Oxide–Dependent Modulation of Endothelial Cell Inflammatory Responses
Authors: Mullick Adam E. , Powers Andrew F. , Kota Rama S. , Tetali Sarada D. , Eiserich Jason P. , Rutledge John C.
Published: December 2006

Objective—

Although apolipoprotein E3 (apoE3) is known to be atheroprotective, its mechanisms of protection in endothelial cells remain unclear.

Methods and Results—

Cultured human aortic endothelial cells were stimulated with tumor necrosis factor (TNF)-α in the presence of human recombinant apoE3 solubilized in dimyristoyl phosphatidylcholine liposomes. Using flow cytometry and real-time polymerase chain reaction, a significant increase of inflammatory cell adhesion proteins (vascular cell adhesion molecule-1 and E-Selectin), and MCP-1, interleukin-8, and intercellular adhesion molecule-1 gene expression was observed within 5 hours of TNF-α exposure, which was markedly attenuated in cells coincubated with apoE3. Treatment with apoE4 resulted in increased inflammatory gene expression relative to either TNF treatment alone or TNF + apoE3 treatment. NO synthase inhibition experiments demonstrated NO to be an active participant in the actions of both TNF and apoE. To clarify the role of NO, dose-response experiments were performed with 0.03 to 300 μmol/L DEA-NONOate. Using flow cytometry and real-time polymerase chain reaction, a modulatory role of NO in TNF-induced endothelial cell activation was observed.

Conclusions—

These data suggest a role of vascular wall apoE3 to balance the intracellular redox state in injured endothelial cells via NO-dependent pathways.
Adenovirus-Mediated Expression of Tissue Factor Pathway Inhibitor-2 Inhibits Endothelial Cell Migration and Angiogenesis
Authors: Ivanciu Lacramioara , Gerard Robert D. , Tang Haiwang , Lupu Florea , Lupu Cristina
Published: December 2006

Objective—Extracellular matrix (ECM) remodeling during angiogenesis is accomplished through plasmin-dependent pericellular proteolysis and through the action of matrix metalloproteinases (MMPs). Because tissue factor pathway inhibitor-2 (TFPI-2), a Kunitz-type protease inhibitor with prominent ECM localization, inhibits plasmin and MMPs activity, we investigated the role of TFPI-2 in endothelial cell (EC) migration and angiogenesis.

Methods and Results—Real-time polymerase chain reaction and immunostaining showed that the expression of TFPI-2 mRNA and protein was upregulated in migrating ECs. The effect of TFPI-2 on angiogenesis was studied in mouse models of Matrigel and polyvinylalcohol sponge implants by overexpressing TFPI-2 through infection with a replication-deficient adenovirus (AdTFPI-2). Using (immuno)fluorescence and confocal microscopy we observed that TFPI-2 reduced neovascularization and promoted ECM deposition. Lateral cell migration and capillary tube formation in vitro also were impaired by TFPI-2, a process reversed by anti–TFPI-2 antibodies. Increased apoptosis occurred both in AdTFPI-2–treated ECs and in the mouse implants. Zymography and assays in the absence of plasminogen confirmed plasmin inhibition as a main mechanism through which TFPI-2 inhibits EC migration.

Conclusions—Our data suggest that TFPI-2 may be an important regulator of aberrant angiogenesis associated with tumor growth/metastasis, cardiovascular diseases, chronic inflammation, or diabetes.
Serum Amyloid P and Cardiovascular Disease in Older Men and Women
Authors: Jenny Nancy Swords , Arnold Alice M. , Kuller Lewis H. , Tracy Russell P. , Psaty Bruce M.
Published: December 2006

Objective—Serum amyloid P (SAP), a pentraxin like C-reactive protein (CRP), functions in innate immunity. However, associations of SAP with cardiovascular disease (CVD) are unknown.

Methods and Results—We examined these associations in the Cardiovascular Health Study using a case–cohort design. Nonexclusive case groups were incident angina (n=523), myocardial infarction (MI; n=308), stroke (n=323), and CVD death (n=288). 786 participants had no events. SAP was correlated with CRP, CVD risk factors (obesity, blood pressure, lipids), common and internal carotid wall thickness, and ankle-brachial index (allP<0.02). In Cox regression models adjusted for age, sex, and ethnicity, a standard deviation increase in SAP (9.8 mg/L) was associated with angina (hazard ratio; 95% confidence interval 1.3; 1.2 to 1.5) and MI (1.3; 1.1 to 1.5), but not stroke (1.1; 0.9 to 1.3) or CVD death (1.1; 0.9 to 1.3). Adding CRP to the models had no significant effect on associations. Adjusting for CVD risk factors slightly attenuated SAP associations with CVD events; however, associations with angina and MI remained significant.

Conclusions—Although both are pentraxins, SAP and CRP may represent different facets of inflammation. The association of SAP with CVD in these older adults further supports the role of innate immunity in atherosclerosis.
Nitroxyl Improves Cellular Heart Function by Directly Enhancing Cardiac Sarcoplasmic Reticulum Ca
2+
Cycling
Authors: Tocchetti Carlo G. , Wang Wang , Froehlich Jeffrey P. , Huke Sabine , Aon Miguel A. , Wilson Gerald M. , Di Benedetto Giulietta , O’Rourke Brian , Gao Wei Dong , Wink David A. , Toscano John P. , Zaccolo Manuela , Bers Donald M. , Valdivia Hector H. , Cheng Heping , Kass David A. , Paolocci Nazareno
Published: December 2006

Heart failure remains a leading cause of morbidity and mortality worldwide. Although depressed pump function is common, development of effective therapies to stimulate contraction has proven difficult. This is thought to be attributable to their frequent reliance on cAMP stimulation to increase activator Ca
2+
. A potential alternative is nitroxyl (HNO), the 1-electron reduction product of nitric oxide (NO) that improves contraction and relaxation in normal and failing hearts in vivo. The mechanism for myocyte effects remains unknown. Here, we show that this activity results from a direct interaction of HNO with the sarcoplasmic reticulum Ca
2+
pump and the ryanodine receptor 2, leading to increased Ca
2+
uptake and release from the sarcoplasmic reticulum. HNO increases the open probability of isolated ryanodine-sensitive Ca
2+
-release channels and accelerates Ca
2+
reuptake into isolated sarcoplasmic reticulum by stimulating ATP-dependent Ca
2+
transport. Contraction improves with no net rise in diastolic calcium. These changes are not induced by NO, are fully reversible by addition of reducing agents (redox sensitive), and independent of both cAMP/protein kinase A and cGMP/protein kinase G signaling. Rather, the data support HNO/thiolate interactions that enhance the activity of intracellular Ca
2+
cycling proteins. These findings suggest HNO donors are attractive candidates for the pharmacological treatment of heart failure.
Antiangiogenic Activity of the MDM2 Antagonist Nutlin-3
Authors: Secchiero Paola , Corallini Federica , Gonelli Arianna , Dell’Eva Raffaella , Vitale Marco , Capitani Silvano , Albini Adriana , Zauli Giorgio
Published: December 2006

Nutlin-3, a nongenotoxic activator of the p53 pathway, dose-dependently (range 0.1 to 10 μmol/L) inhibited the formation of capillaries in an in vivo matrigel assay, as well as the formation of capillary-like structures in an in vitro coculture system composed of endothelial cells surrounded by fibroblasts. In contrast to the chemotherapeutic agent doxorubicin, nutlin-3 showed no induction of apoptosis in vitro either in the cocultures or in isolated vascular endothelial cells, even when used at the highest concentration (10 μmol/L). However, treatment with pharmacological inhibitors of the nuclear factor κB and phosphatidylinositol 3-kinase/Akt pathways sensitized endothelial cells to nutlin-3–induced apoptosis. Although nutlin-3 and doxorubicin induced a comparable p53 accumulation in endothelial cells, nutlin-3 was significantly more efficient than doxorubicin in upregulating the p53 target genes CDKN1A/p21, MDM2, and GDF-15, as well as in inhibiting cell cycle progression. However, the predominant in vitro effect of nutlin-3 was its strong antimigratory activity observed at concentrations significantly lower (0.1 μmol/L) than those required to inhibit endothelial cell cycle progression. Taken together, our data suggest that the antiangiogenic activity of nutlin-3 observed in vivo was mainly attributable to inhibition of endothelial cell migration, to some extent attributable to cell cycle arrest, and to a lesser extent attributable to induction of apoptosis.
Depressive Symptoms and Risk of Stroke
Authors: Salaycik Kimberly J. , Kelly-Hayes Margaret , Beiser Alexa , Nguyen Anh-Hoa , Brady Stephen M. , Kase Carlos S. , Wolf Philip A.
Published: December 2006

Background and Purpose—

Emerging evidence raises the possibility of an association between depression and stroke risk. This study sought to examine whether depressive symptoms are associated with an increased risk of cerebrovascular events in a community-based sample.

Methods—

A prospective study was conducted on 4120 Framingham Heart Study participants aged 29 to 100 years with up to 8 years of follow-up. The Center for Epidemiologic Studies Depression Scale was used to measure depressive symptoms. Incident stroke and transient ischemic attack (TIA) events were assessed by uniform diagnostic criteria. The association between depressive symptoms and risk of stroke/TIA was analyzed with Cox proportional-hazards models, after adjusting for traditional stroke risk factors.

Results—

In participants <65 years, the risk of developing stroke/TIA was 4.21 times greater (
P
=<0.001) in those with symptoms of depression. After adjusting for components of the Framingham Stroke Risk Profile (hazard ratio=3.43, 95% CI=1.60 to 7.36,
P
=0.002) and education (hazard ratio=4.89, 95% CI=2.19 to 10.95), similar results were obtained. In subjects aged 65 and older, depressive symptoms were not associated with an increased risk of stroke/TIA. Taking antidepressant medications did not alter the risk associated with depressive symptoms.

Conclusions—

In this community-based study, depressive symptoms were an independent risk factor for incident stroke/TIA in individuals <65 years. These data suggest that identification of depressive symptoms at younger ages may have an impact on the primary prevention of stroke.
Smoking and the Platelet Fibrinogen Receptor Glycoprotein IIb/IIIA Pl
A1/A2
Polymorphism Interact in the Risk of Lacunar Stroke and Midterm Survival
Authors: Oksala Niku K.J. , Heikkinen Maarit , Mikkelsson Jussi , Pohjasvaara Tarja , Kaste Markku , Erkinjuntti Timo , Karhunen Pekka J.
Published: December 2006

Background and Purpose—

Smoking, increased fibrinogen levels, and platelet activation are related to the risk of ischemic stroke. The platelet fibrinogen receptor glycoprotein (Gp) IIb/IIIa Pl
A1/A2
polymorphism affects the binding of platelets to fibrinogen and is suggested to interact with smoking.

Methods—

We explored the association of smoking and the Pl
A1/A2
polymorphism with ischemic stroke and survival in the Stroke Aging Memory cohort, comprising 486 consecutive patients (55 to 85 years old) who were analyzed 3 months after an ischemic stroke and followed up for 15 months. Stroke subtype determined by magnetic resonance imaging and GpIIb/IIIa Pl
A1/A2
genotype data were available for 272 patients.

Results—

In multivariate analysis, smoking was the only factor related to the risk of lacunar infarcts (odds ratio [OR]=1.87, 95% CI=1.05 to 3.31;
P
=0.033), and it was also a predictor of death (n=24, 8.8%) at 15 months (OR=5.13, 95% CI=1.61 to 16.36;
P
=0.006), along with age (OR=1.10, 95% CI=1.01 to 1.19;
P
=0.008). The GpIIb/IIIa Pl
A1/A2
polymorphism alone showed no association with stroke subtype or survival. However, there was a smoking-by-genotype association with the risk of lacunar infarcts (OR=2.10, 95% CI=0.90 to 4.89;
P
=0.087) and with survival (OR=2.78, 95% CI=0.89 to 8.61;
P
=0.077). Among younger (55 to 69 years) stroke patients, smokers carrying the Pl
A2
allele were at a higher (OR=5.81, 95% CI=1.26 to 26.80;
P
=0.024) risk of lacunar infarcts than noncarrier smokers (OR=3.12, 95% CI=1.06 to 9.24;
P
=0.039). The effect of Pl
A2
and smoking combined on survival was also stronger (OR=8.86, 95% CI=1.68 to 46.55;
P
=0.010) than the effect of smoking alone (OR=5.06, 95% CI=1.20 to 21.35;
P
=0.027).

Conclusions—

Our results indicate that prothrombotic genetic factors may interact with smoking by modifying the stroke phenotype and affecting midterm survival.
Relation of Adult Height With Stroke Mortality in Japan
Authors: Hozawa Atsushi , Murakami Yoshitaka , Okamura Tomonori , Kadowaki Takashi , Nakamura Koshi , Hayakawa Takehito , Kita Yoshikuni , Nakamura Yasuyuki , Okayama Akira , Ueshima Hirotsugu ,   The NIPPON DATA80 Research Group
Published: December 2006

Background and Purpose—

The age-adjusted stroke mortality rate in Japan was the highest in the world from 1950 to the 1970s, but it started to dramatically decrease after 1965. In addition to improved management of high blood pressure, the increase in average height might also contribute to this reduction. The present study investigates whether height is an independent risk for stroke mortality in Japan.

Methods—

Among participants of the National Survey on Cardiovascular Diseases in 1980 who were randomly selected from the Japanese population, we followed up 3969 and 4955 Japanese men and women without prior cardiovascular disease for a maximum of 19 years and observed 158 and 132 stroke deaths.

Results—

Height was inversely correlated with age and with crude stroke mortality. The relationship was attenuated in men when we adjusted for age or other possible confounders (multivariate adjusted relative hazards of a 5-cm increase of height for stroke mortality: 0.92, 95% CI: 0.79 to 1.08). For women, the inverse relationship (relative hazard: 0.77: 95% CI: 0.64 to 0.91) remained after multivariate adjustment. These relationships persisted when we stratified participants by age.

Conclusions—

Height is inversely related to stroke mortality and the relationship is statistically significant among Japanese women.
Performance Study of Mobility Management Schemes in IP-Based Networks
Authors: Lin Yen-Wen , Chang Hsin-Jung
Published: December 2006

Remarkable advances in mobile technologies and wireless communications allow users to access the Internet anywhere at any time. It becomes increasingly essential to support mobility in IP-based networks. The mobile IP is the most widely known mobility management scheme in IP networks. However, some inherent weaknesses of this protocol are only partially solved. Although the route optimization tries to figure out these problems, it cannot manage mobility binding efficiently. In this article, four binding refreshment schemes, including the always-push scheme, the on-demand scheme, the threshold scheme, and the adaptive push scheme, are proposed and evaluated. Among others, the adaptive push scheme is compared with the well-known mobile IP and route optimization. The simulation results show that the adaptive push scheme proposed in this article outperforms the others and significantly reduces the cost of mobility management in IP-based networks.