bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of expiratory muscle fatigue on exercise tolerance and locomotor muscle fatigue in healthy humans
Authors: Taylor Bryan J. , Romer Lee M.
Published: March 2008

High-intensity exercise (≥90% of maximal O2 uptake) sustained to the limit of tolerance elicits expiratory muscle fatigue (EMF). We asked whether prior EMF affects subsequent exercise tolerance. Eight male subjects (means ± SD; maximal O2 uptake = 53.5 ± 5.2 ml·kg−1·min−1) cycled at 90% of peak power output to the limit of tolerance with (EMF-EX) and without (CON-EX) prior induction of EMF and for a time equal to that achieved in EMF-EX but without prior induction of EMF (ISO-EX). To induce EMF, subjects breathed against an expiratory flow resistor until task failure (15 breaths/min, 0.7 expiratory duty cycle, 40% of maximal expiratory gastric pressure). Fatigue of abdominal and quadriceps muscles was assessed by measuring the reduction relative to prior baseline values in magnetically evoked gastric twitch pressure (Pgatw) and quadriceps twitch force (Qtw), respectively. The reduction in Pgatw was not different after resistive breathing vs. after CON-EX (−27 ± 5 vs. −26 ± 6%; P = 0.127). Exercise time was reduced by 33 ± 10% in EMF-EX vs. CON-EX (6.85 ± 2.88 vs. 9.90 ± 2.94 min; P < 0.001). Exercise-induced abdominal and quadriceps muscle fatigue was greater after EMF-EX than after ISO-EX (−28 ± 9 vs. −12 ± 5% for Pgatw, P = 0.001; −28 ± 7 vs. −14 ± 6% for Qtw, P = 0.015). Perceptual ratings of dyspnea and leg discomfort (Borg CR10) were higher at 1 and 3 min and at end exercise during EMF-EX vs. during ISO-EX ( P < 0.05). Percent changes in limb fatigue and leg discomfort (EMF-EX vs. ISO-EX) correlated significantly with the change in exercise time. We propose that EMF impaired subsequent exercise tolerance primarily through an increased severity of limb locomotor muscle fatigue and a heightened perception of leg discomfort.
Spatial and temporal heterogeneity of ventilator-associated lung injury after surfactant depletion
Authors: Otto Cynthia M. , Markstaller Klaus , Kajikawa Osamu , Karmrodt Jens , Syring Rebecca S. , Pfeiffer Birgit , Good Virginia P. , Frevert Charles W. , Baumgardner James E.
Published: March 2008

Volutrauma and atelectrauma have been proposed as mechanisms of ventilator-associated lung injury, but few studies have compared their relative importance in mediating lung injury. The objective of our study was to compare the injury produced by stretch (volutrauma) vs. cyclical recruitment (atelectrauma) after surfactant depletion. In saline-lavaged rabbits, we used high tidal volume, low respiratory rate, and low positive end-expiratory pressure to produce stretch injury in nondependent lung regions and cyclical recruitment in dependent lung regions. Tidal changes in shunt fraction were assessed by measuring arterial Po2 oscillations. After ventilating for times ranging from 0 to 6 h, lungs were excised, sectioned gravitationally, and assessed for regional injury by evaluation of edema formation, chemokine expression, upregulation of inflammatory enzyme activity, and alveolar neutrophil accumulation. Edema formation, lung tissue interleukin-8 expression, and alveolar neutrophil accumulation progressed more rapidly in dependent lung regions, whereas macrophage chemotactic protein-1 expression progressed more rapidly in nondependent lung regions. Temporal and regional heterogeneity of lung injury were substantial. In this surfactant depletion model of acute lung injury, cyclical recruitment produced more injury than stretch.
Body Composition, Changing Physiological Functions and Nutrient Requirements of the Elderly
Authors: Elmadfa Ibrahim , Meyer Alexa L.
Published: March 2008

Age has an important impact on body composition. The decreases of lean body mass and total body water accompanied by an increase of body fat are the most relevant changes leading to a reduction of the basal metabolic rate. Due to this and the fact that elderly people are generally less physically active, energy needs are lower. However, the requirements for most micronutrients are not reduced. Indeed, impaired absorption of some vitamins and minerals like cobalamin and calcium can cause deficiencies. An adequate calcium supply is particularly important as with ongoing age, bone mass decreases as well, making elderly prone to osteoporosis. The reduced ability to synthesize vitamin D and the lower sunlight exposure of many elderly further aggravate this issue. There is evidence to consider the supply of some important dietary antioxidants as critical in some elderly, namely vitamin C and β-carotene as well as zinc. In light of age-related decreases in the activities of antioxidant enzymes, a sufficient supply of dietary antioxidants is important, especially as oxidative damage is thought to contribute to the deteriorating processes associated with aging and promote cardiovascular disease, cognitive disorders, cancer and diabetes mellitus that occur more frequently in older people. The first three are also associated with an insufficiency of folate, another critical nutrient in the elderly. Therefore, dietary guidelines should strive to optimize the immune function and reduce disease risk of the elderly.
Aging, Disability and Frailty
Authors: Topinková Eva
Published: March 2008

Despite multiple and often overlapping definitions of disability and frailty, both are common clinical characteristics of aged individuals though not identical. The geriatric syndrome of frailty is described as status of global impairment of physiological reserves involving multiple organ systems. The clinical correlate of frailty manifests as increased vulnerability, impaired capability to withstand intrinsic and environmental stressors, and limited capacity to maintain physiological and psychosocial homeostasis. Geriatric frailty is found in 20–30% of the elderly population over 75 years and increases with advancing age. It was reported to be associated with long-term adverse health-related outcomes – increased risk of geriatric syndromes, dependency, disability, hospitalization, institutional placement, and mortality. The clinical phenotype of frailty manifests as multi-system pathologies characterized by low physical activity, global weakness with low muscle strength, fatigability/exhaustion, overall slowness particularly of gait, loss of weight among others. These above-mentioned clinical symptoms could be explained by (or related to) some ‘preclinical’ diagnoses such as sarcopenia, osteopenia, nonspecific balance disorders, nutritional problems, and overall deconditioning. More recent studies found the frailty clinical phenotype to be associated with pathologic laboratory markers (IL-6, CRP, 25-hydroxyvitamin D, IGF-1, D-dimers), which suggest possible pathogenesis involving hormonal dysregulation, immuno-aging, pro-coagulation and pro-inflammatory status. In the article, current recommendations for future research strategies of frailty syndrome will be discussed.
Nutritional Supplementation in Community-Dwelling Elderly People
Authors: Mucci Elena , Jackson S.H.D.
Published: March 2008

There is a large evidence base for nutritional intervention in acutely ill and post-operative hospitalised patients, but the evidence base for nursing home (NH) residents is small. The prevalence of poor nutrition in NHs is high and baseline nutrition appears to be an important determinant of response to nutritional intervention. Residents with mininutritional assessment (MNA) scores above 23.5 tend to show less response than those with lower scores. This relates in part to failure to increase intake in the better nourished as well as to actual response to increased intake. At the low end of the MNA spectrum, the increasing prevalence of multiple pathologies tends to result in a reduced response, but randomised controlled studies in this group is probably not ethical. Most studies have tended to investigate the intermediate group with MNA scores of 17–23.5 or equivalent using other scales. Interventions have usually resulted in increased intake of calories and micronutrients. Other end points have variously shown responses including weight, immunological measures, infection rates, decubitus ulcers, falls and fracture rates. Many studies have been too small to demonstrate benefit and some are likely to have suffered from type l errors – showing benefit by chance. Poorly quantifiable variables likely to be of importance include the local environment and catering as well as pathophysiological variability.
Antimicrobial Activities of Twenty Lysine-Peptoid Hybrids against Clinically Relevant Bacteria and Fungi
Authors: Ryge Trine S. , Frimodt-Møller Niels , Hansen Paul R.
Published: March 2008

Background: This paper describes the antimicrobial activities of 20 lysine-peptoid hybrids against a selection of clinically relevant bacteria and fungi. Methods: Minimal inhibitory concentrations were determined against methicillin-susceptible Staphylococcus aureus (ATCC 29213), methicillin-resistant S. aureus (ATCC 33591), vancomycin-intermediate S. aureus (ATCC 700699 MU50), vancomycin-resistant Enterococcus faecium (ATCC 700221), Pseudomonas aeruginosa (ATCC 27853), Salmonella typhimurium (clinical isolate), Klebsiella pneumoniae (clinical isolate), amphotericin-B-resistant C. albicans (ATCC 200955) and Cryptococcus neoformans (clinical isolate). Results: The lysine-peptoid hybrids proved to be active against all strains tested, except K. pneumoniae. For each susceptible strain, we identified at least 4 lysine-peptoid hybrids showing excellent activity. The most active compounds displayed minimal inhibitory concentrations ranging from ≤1.6 to 6.25 µM. Conclusion: This study demonstrates that lysine-peptoid hybrids show activity against drug-resistant pathogens.
Inhaled Nitric Oxide for the Treatment of Preterm Infants with Respiratory Distress Syndrome
Authors: Dani Carlo , Bertini Giovanna
Published: March 2008

Many authors have hypothesized that inhaled nitric oxide (iNO) might acutely improve oxygenation in preterm neonates with infant respiratory distress syndrome (iRDS) and decrease the risk of bronchopulmonary dysplasia. The studies on the effects of iNO in preterm infants with iRDS have given contradictory results. We report their main methodological characteristics and the observed effects of iNO in preterm infants. Moreover, we discuss the infants’ age at the beginning of the study, the dose and duration of iNO therapy, its potential effect on neurodevelopment, its relationship with surfactant properties, and the need to identify patients who are likely to respond to this therapy. We advise caution against the widespread use of iNO in preterm infants with iRDS. At present, it appears to be premature to have specific recommendations regarding the indications for iNO therapy in this group of patients. The conclusion of current trials and the follow-up studies of recently completed trials will give further data to guide neonatologists’ decisions, and until then it is likely that clinicians will continue to make case-by-case decisions for the treatment of iNO in preterm infants with hypoxia that is unresponsive to other therapies. However, this decision should always be discussed with the parents.
Cultural and Language Differences in Voice Quality Perception: A Preliminary Investigation Using Synthesized Signals
Authors: Yiu Edwin M.-L. , Murdoch Bruce , Hird Kathryn , Lau Polly , Ho Elaine Mandy
Published: March 2008

Background: Perceptual voice evaluation is a common clinical tool. However, to date, there is no consensus yet as to which common quality should be measured. Some available evidence shows that voice quality is a language-specific property which may be different across different languages. The familiarity of a language may affect the perception and reliability in rating voice quality. Aims: The present study set out to investigate the effects of listeners’ cultural and language backgrounds on the perception of voice qualities. Methods and Procedures: Forty speech pathology students from Australia and Hong Kong were asked to rate the breathy and rough qualities of synthesized voice signals in Cantonese and English. Outcome and Results: Results showed that the English stimulus sets as a whole were rated less severely than the Cantonese stimuli by both groups of listeners. In addition, the male Cantonese and English breathy stimuli were rated differently by the Australian and Hong Kong listeners. Conclusions and Implications: These results provided some evidence to support the claim that cultural and language backgrounds of the listeners would affect the perception for some voice quality types. Thus, the cultural and language backgrounds of judges should be taken into consideration in clinical voice evaluation.
Increased Matrix Metalloproteinase 2 Activity in the Human Internal Mammary Artery Is Associated with Ageing, Hypertension, Diabetes and Kidney Dysfunction
Authors: Chung A.W. , Booth A.D. , Rose C. , Thompson C.R. , Levin A. , van Breemen C.
Published: March 2008

Dysregulation of matrix metalloproteinase (MMP)-2 in the vasculature has been suggested to be associated with increased prevalence of cardiovascular disease and renal injury. In this descriptive study, we hypothesized that arterial MMP-2 activity is elevated in the presence of cardiovascular risk factors such as diabetes, hypertension, smoking and ageing, and that it correlates with the degree of kidney function. MMP-2 activity in internal mammary arteries (n = 37) was measured using gelatinolytic zymography, and cutoffs were determined using sample-derived medians. Patient demographics and clinical data were analyzed, and the estimated glomerular filtration rate (eGFR) was calculated. High MMP-2 activity (>60,000 units) was associated with age, hypertension and diabetes (p = 0.0034, 0.06 and 0.0034, respectively). Multivariate analysis showed that age and diabetes were independent predictors of high MMP-2 activity. There is a trend towards increased MMP-2 activity and reduced eGFR (p = 0.010). The current exploratory work describes that the activity of MMP-2 in the internal mammary artery is correlated with age, hypertension, diabetes and eGFR. It is the first report suggesting that MMP-2 in the arterial vasculature could be the possible mediator crucial in linking the progression of kidney function to cardiovascular disease.
Late Posttraumatic Meningitis with Concealed CSF Otorrhea
Authors: Lui Tai-Ngar , Lee Shih-Tseng
Published: March 2008

An 11-year-old girl with repeated pneumococcal meningitis after head injury is reported. High resolution CT scan with metrizamide cisternogram disclosed a fracture in petrous bone with collection of contrast medium in middle ear. Operative repair of the dura defect successfully stopped further intracranial infection. In cases of late posttraumatic infection, aggressive survey of the skull base is indicated.
Stereotactic Resection of Pediatric Vascular Malformations
Authors: Partington Michael D. , Davis Dudley H. , Kelly Patrick J.
Published: March 2008

The technique of computer-assisted stereotactic resection of intra-axial neoplasms can also be used in the treatment of vascular malformations. We report a series of 12 pediatric patients with supratentorial lesions who underwent stereotactic resections between 1985 and 1988. There were 5 boys and 7 girls, with mean age 8 years (range 3–16). Epilepsy was the presenting symptom in 8 children, hemorrhage in 3, and in 1 the lesion was incidentally diagnosed. Seven lesions were angiographically occult. All lesions were resected without mortality or morbidity. Seizures resolved in 7 of 8 cases, with the remaining patient experiencing a reduction in seizure frequency. Illustrative cases are presented.
Use of Epidural Morphine for Control of Postoperative Pain in Selective Dorsal Rhizotomy for Spasticity
Authors: Sparkes Mary Louise , Klein Alan S. , Duhaime Ann-Christine , Mickle Parker
Published: March 2008

Postoperative pain control can be a major problem after selective dorsal rhizotomy for the treatment of spasticity. We report the use of epidural morphine delivered via a catheter placed at surgery for postoperative analgesia in 28 consecutive patients undergoing this procedure. Pain was well controlled using this technique, and no patients required concomitant parenteral analgesia. There were no instances of respiratory depression, wound infection, or central nervous system depression, and the patients were easily mobilized in the early postoperative period. Epidural morphine is concluded to be a safe and very efficacious method of analgesia after selective dorsal rhizotomy.
Effects of Statins on Adipose Tissue Inflammation
Authors: Abe Manabu , Matsuda Morihiro , Kobayashi Hironori , Miyata Yugo , Nakayama Yuki , Komuro Ryutaro , Fukuhara Atsunori , Shimomura Iichiro
Published: March 2008

Objectives—

Macrophage-mediated chronic inflammation of adipose tissue is causally linked to insulin resistance in obesity. The beneficial effects of 3-hydroxy-3-methylglutaryl (HMG) coenzyme A (CoA) reductase inhibitors (statins) on glucose metabolism have been suggested, but the effects of these agents on adipose tissue inflammation are unclear. The aim of the present study is to define the effects of statins on adipose tissue inflammation and macrophages.

Methods and Results—

Pravastatin or pitavastatin treatment of obese mice attenuated an increase in mRNA expressions of proinflammatory genes, including MCP1 and IL6, in adipose tissue. The supernatant of TLR4-stimulated RAW264 macrophages strongly induced the expression of these genes in 3T3-L1 adipocytes, which was inhibited by pretreatment of macrophages with either statin. Statins inhibited TLR4-mediated activation of interferon (IFN) regulatory factor (IRF)3 by either lipopolysaccharide (LPS) or palmitic acid, resulting in suppression of IFN-β expression, but not that of NF-κB or JNK. Moreover, statins strongly downregulated TLR3-mediated gene expressions by poly(I:C), but not TLR2-stimulation by zymosan A. Neutralization of IFN-β attenuated proinflammatory activities of the macrophage supernatant.

Conclusions—

Statins partially attenuated the development of adipose tissue inflammation in obese mice, which might be associated with an inhibitory effect of statins on TLR4-triggered expression of IFN-β via MyD88-independent signaling pathway in macrophages.
Phosphatidylinositol-3-Kinase-γ Is Integral to Homing Functions of Progenitor Cells
Authors: Chavakis Emmanouil , Carmona Guillaume , Urbich Carmen , Göttig Stephan , Henschler Reinhard , Penninger Josef M. , Zeiher Andreas M. , Chavakis Triantafyllos , Dimmeler Stefanie
Published: March 2008

Endothelial progenitor cells (EPCs) and hematopoietic progenitor cells are recruited to ischemic regions, improving neovascularization. β1 and β2 integrins play a crucial role for progenitor cell homing to ischemic tissues. Integrin activity is regulated by chemokines and their respective G protein–coupled receptors. The phosphatidylinositol-3-kinase catalytic subunit γ (PI3Kγ) is the PI3K isoform that selectively transduces signals from G protein–coupled receptors. Here, we investigated the role of PI3Kγ as a signaling intermediate in the chemokine-induced integrin-dependent homing functions of progenitor cells. A pharmacological PI3Kγ inhibitor significantly reduced chemokine-induced chemotaxis and stromal cell–derived factor (SDF)1α-induced transmigration of human EPCs. Moreover, the PI3Kγ inhibitor significantly reduced SDF1α-induced adhesion of EPCs to intercellular adhesion molecule-1 and human umbilical vein endothelial cell monolayers. These findings were corroborated with Lin
−
bone marrow–derived progenitor cells from PI3Kγ-deficient mice that displayed reduced SDF1α-induced migration and intercellular adhesion molecule-1 adhesion as compared with wild-type cells. Pharmacological inhibition or genetic ablation of PI3Kγ reduced SDF1α-induced integrin activation in human EPCs and in murine Lin
−
BM-derived progenitor cells, respectively. In vivo, the homing of PI3Kγ-deficient Lin
−
progenitor cells to ischemic muscles after intravenous infusion in the model of hindlimb ischemia and their neovascularization-promoting capacity was reduced as compared with wild-type cells. In conclusion, PI3Kγ is integral to the integrin-dependent homing of progenitor cells.
Epac Mediates β-Adrenergic Receptor–Induced Cardiomyocyte Hypertrophy
Authors: Métrich Mélanie , Lucas Alexandre , Gastineau Monique , Samuel Jane-Lise , Heymes Christophe , Morel Eric , Lezoualc’h Frank
Published: March 2008

Cardiac hypertrophy is promoted by adrenergic overactivation and can progress to heart failure, a leading cause of mortality worldwide. Although cAMP is among the most well-known signaling molecules produced by β-adrenergic receptor stimulation, its mechanism of action in cardiac hypertrophy is not fully understood. The identification of Epac (exchange protein directly activated by cAMP) proteins as novel sensors for cAMP has broken the dogma surrounding cAMP and protein kinase A. However, their role and regulation in the mature heart remain to be defined. Here, we show that cardiac hypertrophy induced by thoracic aortic constriction increases Epac1 expression in rat myocardium. Adult ventricular myocytes isolated from banded animals display an exaggerated cellular growth in response to Epac activation. At the molecular level, Epac1 hypertrophic effects are independent of its classic effector, Rap1, but rather involve the small GTPase Ras, the phosphatase calcineurin, and Ca
2+
/calmodulin-dependent protein kinase II. Importantly, we find that in response to β-adrenergic receptor stimulation, Epac1 activates Ras and induces adult cardiomyocyte hypertrophy in a cAMP-dependent but protein kinase A–independent manner. Knockdown of Epac1 strongly reduces β-adrenergic receptor–induced hypertrophic program. Finally, we report for the first time that Epac1 is mainly expressed in human heart as compared with Epac2 isoform and is increased in heart failure. Taken together, our data demonstrate that the guanine nucleotide exchange factor Epac1 contributes to the hypertrophic effect of β-adrenergic receptor in a protein kinase A–independent fashion and may, therefore, represent a novel therapeutic target for the treatment of cardiac disorders.
Beneficial Effect of the Central Nervous System β-Adrenoceptor Blockade on the Failing Heart
Authors: Gourine Andrey , Bondar Svetlana I. , Spyer K. Michael , Gourine Alexander V.
Published: March 2008

Heart failure patients are routinely given β-adrenoceptor antagonists (β-blockers), although the mechanism(s) underlying their beneficial effects is not fully resolved. It is not entirely clear how long-term application of negative inotropic compounds improves cardiac performance, slows remodeling processes, and decreases mortality. All β-blockers, which produce a beneficial effect in heart failure, have in common a high degree of lipophilicity and, therefore, have the ability to cross the blood–brain barrier. Here, we show that blockade of β-adrenoceptors directly in the brain (chronic intracerebroventricular administration of metoprolol) attenuates the progression of left ventricular remodeling in a rat model of myocardial infarction-induced heart failure. These results provide the first direct evidence that the action of certain β-blockers in the brain could contribute to their beneficial effect on the failing heart.
Oxygen Deprivation Triggers Upregulation of Early Growth Response-1 by the Receptor for Advanced Glycation End Products
Authors: Chang Jong Sun , Wendt Thoralf , Qu Wu , Kong Linghua , Zou Yu Shan , Schmidt Ann Marie , Yan Shi-Fang
Published: March 2008

Myocardial infarction, stroke, and venous thromboembolism are characterized by oxygen deprivation. In hypoxia, biological responses are activated that evoke tissue damage. Rapid activation of early growth response-1 in hypoxia upregulates fundamental inflammatory and prothrombotic stress genes. We probed the mechanisms mediating regulation of early growth response-1 and demonstrate that hypoxia stimulates brisk generation of advanced glycation end products (AGEs) by endothelial cells. Via AGE interaction with their chief signaling receptor, RAGE, membrane translocation of protein kinase C-βII occurs, provoking phosphorylation of c-Jun NH
2
-terminal kinase and increased transcription of early growth response-1 and its downstream target genes. These findings identify RAGE as a master regulator of tissue stress elicited by hypoxia and highlight this receptor as a central therapeutic target to suppress the tissue injury–provoking effects of oxygen deprivation.
Sphingosine-1-Phosphate Induces an Antiinflammatory Phenotype in Macrophages
Authors: Hughes Jeniter E. , Srinivasan Suseela , Lynch Kevin R. , Proia Richard L. , Ferdek Pawel , Hedrick Catherine C.
Published: March 2008

Activated macrophages acquire a proinflammatory (classic) or antiinflammatory (alternative) phenotype that influences atherosclerosis. The present study investigated whether sphingosine-1-phosphate (S1P), with its known antiinflammatory effects, could regulate the inflammatory phenotype of lipopolysaccharide (LPS)-stimulated mouse macrophages. Activation of macrophages by LPS significantly increases proinflammatory cytokine secretion. Pretreatment of macrophages with 500 nmol/L S1P markedly reduced LPS-mediated secretion of tumor necrosis factor-α, monocyte chemoattractant protein-1, and interleukin-12. Such antiinflammatory actions were also evident in LPS-stimulated macrophages treated with the S1P1 receptor–specific agonist SEW2871. Pharmacological antagonism of the S1P1 receptor on macrophages using the S1P1-specific antagonist VPC44116 also blocked proinflammatory cytokine secretion in response to LPS. Studies using bone marrow–derived macrophages from S1P2-deficient mice revealed that the S1P2 receptor did not play a pivotal role in this process. Thus, activation of the S1P1 receptor in mouse macrophages limits the expression of proinflammatory cytokines. Furthermore, we demonstrated that S1P increased arginase I activity and inhibited LPS-induced inducible NO synthase activity in LPS-treated macrophages, again through S1P1 receptor activation on macrophages. Analysis of a 1.7-kb region of the murine inducible NO synthase promoter revealed the presence of putative nuclear factor κB, activator protein-1, and STAT-1 response elements. Using inducible NO synthase promoter-reporter constructs, we found that S1P significantly reduced the nuclear factor κB–mediated induction of inducible NO synthase. These findings demonstrate an important role for S1P in the regulation of macrophage phenotypic switching. Therefore, we conclude that S1P promotes the production of an alternative antiinflammatory macrophage phenotype through activation of the macrophage S1P1 receptor.
Cigarette Smoking, Systolic Blood Pressure, and Cardiovascular Diseases in the Asia-Pacific Region
Authors: Nakamura Koshi , Barzi Federica , Lam Tai-Hing , Huxley Rachel , Feigin Valery L. , Ueshima Hirotsugu , Woo Jean , Gu Dongfeng , Ohkubo Takayoshi , Lawes Carlene M.M. , Suh Il , Woodward Mark
Published: March 2008

Background and Purpose—

Smoking and increased levels of blood pressure (BP) substantially increase the risk of cardiovascular diseases (CVD). If these 2 risk factors have a synergistic impact on cardiovascular events, lowering BP and quitting smoking will contribute more to reducing CVD than would be expected from ignoring their interaction.

Methods—

Individual participant data were combined from 41 cohorts, involving 563 144 participants (82% Asian). During a median of 6.8 years follow-up, 4344 coronary heart disease (CHD) and 5906 stroke events were recorded. Repeat measures of systolic blood pressure (SBP) were used to adjust for regression dilution bias. Hazard ratios (HRs) and 95% confidence intervals (CIs) for SBP by cigarette smoking status were estimated from Cox proportional hazard models adjusted for age and stratified by study and sex.

Results—

Data suggested a log-linear relationship between SBP and all subtypes of CVD. The HRs relating SBP to both CHD and ischemic stroke were broadly similar irrespective of smoking status (
P
≥0.1). For hemorrhagic stroke (intracerebral hemorrhage), the HRs (95% CIs) for an additional 10 mm Hg increment in SBP were 1.81 (1.73 to 1.90) for present smokers and 1.66 (1.59 to 1.73) for nonsmokers (
P
=0.003). For every subtype of cardiovascular events, similar results were found for analyses involving only fatal events.

Conclusions—

Smoking exacerbated the impact of SBP on the risk of hemorrhagic stroke. Although quitting smoking and lowering BP are both crucial for prevention of CVD, combining the 2 could be expected to have extra beneficial effect on preventing hemorrhagic stroke.
Misclassified Tissue Volumes in Alzheimer Disease Patients With White Matter Hyperintensities
Authors: Levy-Cooperman Naama , Ramirez Joel , Lobaugh Nancy J. , Black Sandra E.
Published: March 2008

Background and Purpose—

MRI-based quantification of gray and white matter volume is common in studies involving elderly patient populations. The aim of the present study was to describe the effects of not accounting for subcortical white matter hyperintensities (WMH) on tissue volumes in Alzheimer Disease patients with varying degrees of WMH (mild: n=19, moderate: n=22, severe: n=18).

Methods—

An automated tissue segmentation protocol that was optimized for an elderly population, a brain regional parcellation procedure, and a lesion segmentation protocol were applied to measure tissue volumes (whole brain and regional lobar volumes) with and without lesion segmentation to quantify the volume of misclassified tissue.

Results—

After application of the tissue segmentation protocol and lesion analysis, mean total percentage misclassified volume across all subjects was 2% (17.9 cm
3
) of whole brain volume (corrected for total intracranial capacity). Mean percentage of misclassified tissue volumes for the severe group was 4.8% of whole brain, which translates to a mean volume 42.2 cm
3
. Gray matter volume was most overestimated in the severe group, where 6.4% of the total gray matter volume was derived from misclassified WMH. The regional analysis showed that frontal (41%, 7.4 cm
3
) and inferior parietal (18%, 3.25 cm
3
) lobes were most affected by tissue misclassification.

Conclusion—

MRI-based volumetric studies of Alzheimer Disease that do not account for WMH can expect an erroneous inflation of gray or white matter volumes, especially in the frontal and inferior parietal regions. To avoid this source of error, MRI-based volumetric studies in patient populations susceptible to hyperintensities should include a WMH segmentation protocol.
MMP-9–Positive Neutrophil Infiltration Is Associated to Blood–Brain Barrier Breakdown and Basal Lamina Type IV Collagen Degradation During Hemorrhagic Transformation After Human Ischemic Stroke
Authors: Rosell Anna , Cuadrado Eloy , Ortega-Aznar Arantxa , Hernández-Guillamon Mar , Lo Eng H. , Montaner Joan
Published: March 2008

Background and Purpose—

An abnormal expression of some matrix metalloproteinases (MMPs) is related with hemorrhagic transformation events after stroke. Our aim was to investigate MMP-2 and MMP-9 in the ischemic brain and its relation with blood–brain barrier breakdown after hemorrhagic transformation in human stroke.

Methods—

We assessed 5 cases of fatal ischemic strokes with hemorrhagic complications; brain samples were obtained from infarct, hemorrhagic, and contralateral tissue. MMP-9 and MMP-2 content was analyzed by zymography and immunohistochemistry was performed to localize MMP-9 and to assess collagen IV integrity in the basal lamina. Laser capture microdissection was performed to isolate blood–brain barrier vessels to study these MMPs.

Results—

Overall, MMP-9 levels were higher both in hemorrhagic and nonhemorrhagic infarcted tissue compared to contralateral areas (
P
<0.0001 and
P
<0.05). Moreover, levels of the cleaved MMP-9 85kDa-form were significantly elevated in the hemorrhagic compared to nonhemorrhagic and contralateral areas (
P
=0.033 and
P
<0.0001). No changes were found for MMP-2 content. Immunostaining revealed a strong MMP-9–positive neutrophil infiltration surrounding brain microvessels associated with severe basal lamina type IV collagen degradation and blood extravasation. Microdissection confirmed that content of MMP-9 was similarly high in microvessel endothelium from hemorrhagic and infarcted areas compared to contralateral hemisphere vessels (
P
<0.05), pointing to neutrophils surrounding dissected microvessels as the main source of MMP-9 in hemorrhagic areas.

Conclusions—

Our results show a strong neutrophil infiltration in the infarcted and hemorrhagic areas with local high MMP-9 content closely related to basal lamina collagen IV degradation and blood–brain barrier breakdown. Microvessel and inflammatory MMP-9 response are associated with hemorrhagic complications after stroke.
Induction of Immunologic Tolerance to Myelin Basic Protein Prevents Central Nervous System Autoimmunity and Improves Outcome After Stroke
Authors: Gee J. Michael , Kalil Angela , Thullbery Matthew , Becker Kyra J.
Published: March 2008

Background and Purpose—

Animals subjected to an inflammatory insult at the time of stroke are predisposed to the development of an inflammatory autoimmune response to brain. This response is associated with worse neurological outcome. Because induction of immunologic tolerance to brain antigens before stroke onset is associated with improved outcome, we sought to determine whether this paradigm could prevent the deleterious autoimmune response to brain provoked by an inflammatory stimulus at the time of ischemia.

Methods—

Male Lewis rats were tolerized to myelin basic protein (MBP) or ovalbumin by intranasal administration before middle cerebral artery occlusion. At the time of reperfusion, all animals received lipopolysaccharide (1 mg/kg intraperitoneal). Behavioral tests were performed at set time intervals.

Results—

One month after middle cerebral artery occlusion, lymphocytes from the spleens of MBP-tolerized animals were less likely to evidence an autoimmune response and more likely to evidence a regulatory response (T
reg
) toward MBP than those from ovalbumin-tolerized animals. Animals that had an inflammatory response toward MBP (a T
h
1 response) performed worse on behavioral tests than those that did not. Fractalkine, a surrogate marker of inflammation, was elevated in animals with a T
h
1 response to MBP.

Conclusions—

These data extend our previous findings and suggest that deleterious autoimmunity to brain antigens can be prevented by prophylactically inducing regulatory T-cell responses to those antigens.
Albumin Therapy Augments the Effect of Thrombolysis on Local Vascular Dynamics in a Rat Model of Arteriolar Thrombosis
Authors: Park Hee-Pyoung , Nimmagadda Anitha , DeFazio Richard A. , Busto Raul , Prado Ricardo , Ginsberg Myron D.
Published: March 2008

Background and Purpose—

Results of our recent pilot clinical trial suggest that the efficacy of thrombolytic therapy in acute ischemic stroke may be enhanced by the coadministration of high-dose albumin. Here, we explored the microvascular hemodynamic effects of this combined therapy in a laboratory model of cortical arteriolar thrombosis.

Methods—

We studied the cortical microcirculation of physiologically monitored rats in vivo by two-photon laser-scanning microscopy after plasma-labeling with fluorescein-dextran. We induced focal thrombosis in 30- to 50-μm cortical arterioles by laser irradiation and measured arteriolar flow velocity by repeated line-scanning. At 30 minutes post-thrombosis, we treated animals with the thrombolytic agent, reteplase, which was coadministered with either human albumin, 2 g/kg, or with saline control.

Results—

Baseline arteriolar flow velocity averaged 3.8±0.7 mm/s, was immediately reduced by thrombosis to 22% to 25% of control values, and remained unchanged before treatment. Subthrombolytic doses of reteplase combined with saline led to a median increase in flow velocity to 37% of control distal to the thrombus (
P
=nonsignificant versus pretreatment). By contrast, reteplase combined with albumin therapy resulted in a prompt, highly significant increase of median flow velocity to 58% of control levels (
P
=0.013 versus reteplase+saline), which remained significantly higher than the reteplase+saline group at multiple time-points over the subsequent hour.

Conclusions—

The beneficial effect of subthrombolytic doses of reteplase on microvascular hemodynamics distal to a cortical arteriolar thrombosis is markedly enhanced by the coadministration of high-dose albumin therapy; these results have important clinical implications for the management of patients with acute ischemic stroke.
Predictors and Outcomes of Intraprocedural Rupture in Patients Treated for Ruptured Intracranial Aneurysms
Authors: Elijovich Lucas , Higashida Randall T. , Lawton Michael T. , Duckwiler Gary , Giannotta Steven , Johnston S. Claiborne
Published: March 2008

Background and Purpose—

Intraprocedural rupture (IPR) is a well known complication of intracranial aneurysm treatment. Risks and predictors of IPR and its impact on outcome have not been clearly established.

Methods—

Potential predictors of IPR were evaluated in patients treated in the Cerebral Aneurysm Rerupture After Treatment (CARAT) study using multivariate logistic regression with stepwise elimination stratified by treatment modality. Periprocedural death or disability was defined as death or a change of ≥2 points on the Modified Rankin Scale at discharge compared to before treatment.

Results—

IPR occurred in 14.6% of 1010 patients (299 coiled, 711 clipped): 19% with clipping and 5% with coiling (
P
<0.001). Among those clipped, 31% with IPR had periprocedural death or disability compared to 18% without IPR (
P
=0.001); among those coiled, 63% with IPR had periprocedural death or disability compared to 15% without IPR (
P
<0.001). Overall, coronary artery disease and initial lower Hunt and Hess Grade were independent predictors of IPR. For those undergoing coiling, independent predictors of IPR were Asian race, black race, COPD, and lower initial Hunt and Hess Grade. Among those undergoing clipping, hyperlipidemia and lower initial Hunt and Hess Grade were both independent predictors of IPR.

Conclusions—

IPR was common in patients undergoing treatment of ruptured aneurysms, particularly with surgical clipping. The frequency of IPR with new disability was similar in the surgical and endovascular treatment groups. Coronary artery disease, hyperlipidemia, race, COPD, and lower Hunt and Hess Grade were associated with greater risk of IPR, which may reflect differences in vessel fragility but requires further confirmation.
Metabolic Syndrome Is Associated With Silent Ischemic Brain Lesions
Authors: Bokura Hirokazu , Yamaguchi Shuhei , Iijima Kenichi , Nagai Atsushi , Oguro Hiroaki
Published: March 2008

Background and Purpose—

Metabolic syndrome (MetS) is a recognized risk factor for stroke, but it is unclear whether MetS is also related to subclinical ischemic lesions. We examined the association of MetS with the prevalence of silent brain infarction, periventricular hyperintensity, and subcortical white matter lesions in healthy adults.

Methods—

We conducted a cross-sectional study in 1151 Japanese healthy subjects. Three types of silent lesions were assessed by MRI scans. MetS was diagnosed using the criteria by the National Cholesterol Education Adult Treatment Panel III.

Results—

After adjusting for age and other factors, MetS was significantly associated with silent brain infarction, periventricular hyperintensity and subcortical white matter lesions. Among the MetS components, elevated blood pressure was commonly associated with all types of lesions. Dyslipidemia and elevated fasting glucose levels were associated with subcortical white matter lesions and periventricular hyperintensities, respectively. Positive trends were observed between the number of MetS components and prevalence of silent lesions.

Conclusions—

MetS is associated with the prevalence of silent lesions independent of other risk factors. The clustering of MetS components tends to increase the prevalence of silent lesions.
Modeling Local Coherence: An Entity-Based Approach
Authors: Barzilay Regina , Lapata Mirella
Published: March 2008

This article proposes a novel framework for representing and measuring local coherence. Central to this approach is the entity-grid representation of discourse, which captures patterns of entity distribution in a text. The algorithm introduced in the article automatically abstracts a text into a set of entity transition sequences and records distributional, syntactic, and referential information about discourse entities. We re-conceptualize coherence assessment as a learning task and show that our entity-based representation is well-suited for ranking-based generation and text classification tasks. Using the proposed representation, we achieve good performance on text ordering, summary coherence evaluation, and readability assessment.
Teleconnection between NAO and Climate Downstream of the Tibetan Plateau
Authors: Li Jian , Yu Rucong , Zhou Tianjun
Published: March 2008

Analysis of the monthly NCEP–NCAR reanalysis data and station data reveals a teleconnection pattern (NAULEA) that links climate changes over the North Atlantic and Eurasia. The NAULEA pattern has five action centers. It extends from the North Atlantic to northwestern Europe, and then stretches eastward to the Urals, with its eastern end over North China. Certain climate changes over East Asia, such as the cooling changes in both the upper troposphere and surface in the last few decades of the twentieth century, can be attributed to the NAULEA pattern anomalies and traced upstream to the North Atlantic. The NAULEA pattern is suggested to be another NAO-related teleconnection pattern. Compared with the pattern with the Asian jet waveguide path, which leads to temperature anomalies over northeastern Asia, the NAULEA pattern with a high-latitude path exerts stronger influences on the climate of southwestern China.
A New Sea Surface Temperature and Sea Ice Boundary Dataset for the Community Atmosphere Model
Authors: Hurrell James W. , Hack James J. , Shea Dennis , Caron Julie M. , Rosinski James
Published: March 2008

A new surface boundary forcing dataset for uncoupled simulations with the Community Atmosphere Model is described. It is a merged product based on the monthly mean Hadley Centre sea ice and SST dataset version 1 (HadISST1) and version 2 of the National Oceanic and Atmospheric Administration (NOAA) weekly optimum interpolation (OI) SST analysis. These two source datasets were also used to supply ocean surface information to the 40-yr European Centre for Medium-Range Weather Forecasts Re-Analysis (ERA-40). The merged product provides monthly mean sea surface temperature and sea ice concentration data from 1870 to the present: it is updated monthly, and it is freely available for community use. The merging procedure was designed to take full advantage of the higher-resolution SST information inherent in the NOAA OI.v2 analysis.
A Study on Optimum Tilt Angle for Wind Estimation Using Indian MST Radar
Authors: Anandan V. K. , Rao I. Srinivasa , Reddy P. Narasimha
Published: March 2008

The effect of tilt angle on horizontal wind estimation is studied using Indian mesosphere–stratosphere–troposphere (MST) radar located at Gadanki (13.45°N, 79.18°E). It operates in Doppler beam swinging (DBS) mode with a beamwidth of 3°. Horizontal winds are computed for different tilt angles from 3° to 15° with an increment of 3° from a height range of 3.6–18 km. The effective beam pointing angle (θeff) is calculated to determine the effect of aspect sensitivity on the determination of horizontal wind components. For different tilt angles radar-derived winds are compared with simultaneous GPS sonde wind measurements, which were launched from a nearby site. The first method utilizes direct comparison of radar-derived winds with those of GPS sondes using the actual beam pointing angle; the second method uses the effective beam pointing angle derived from the ratios of two oblique beams. For this study a variety of statistics were explored in terms of standard deviation, correlation coefficient, and percentage error. From the results it is observed that in agreement with previous studies, the effective beam pointing angle deviates from the actual beam pointing angle, which results in the underestimation of horizontal wind components, and also when tilt angle is close to zenith and far from zenith, the estimation of horizontal winds is found to be far from true values at different heights. Radar wind estimation has better agreement with GPS sonde measurement when the off-zenith angle is around 10°. It is also found that correction to the actual beam pointing angle provides 3%–6% improved agreement between the radar and GPS wind measurements.
Skill of Multimodel ENSO Probability Forecasts
Authors: Tippett Michael K. , Barnston Anthony G.
Published: March 2008

The cross-validated hindcast skills of various multimodel ensemble combination strategies are compared for probabilistic predictions of monthly SST anomalies in the ENSO-related Niño-3.4 region of the tropical Pacific Ocean. Forecast data from seven individual models of the Development of a European Multimodel Ensemble System for Seasonal-to-Interannual Prediction (DEMETER) project are used, spanning the 22-yr period of 1980–2001. Skill of the probabilistic forecasts is measured using the ranked probability skill score and rate of return, the latter being an information theory–based measure. Although skill is generally low during boreal summer relative to other times of the year, the advantage of the model forecasts over simple historical frequencies is greatest at this time. Multimodel ensemble predictions, even those using simple combination methods, generally have higher skill than single model predictions, and this advantage is greater than that expected as a result of an increase in ensemble size. Overall, slightly better performance was obtained using combination methods based on individual model skill relative to methods based on the complete joint behavior of the models. This finding is attributed to the comparatively large expected sampling error in the estimation of the relations between model errors based on the short history. A practical conclusion is that, unless some models have grossly low skill relative to the others, and until the history is much longer than two to three decades, equal, independent, or constrained joint weighting are reasonable courses.
The Cost—Benefit Framework and Perceptions of Decision Strategies
Authors: Chu P.C. , Spires Eric E.
Published: March 2008

Cost—benefit theories of decision strategy choice provide a conceptual foundation for studying human decision behavior. Central to cost—benefit theories are decision makers' perceptions of the efficacy and effort of various decision strategies. The authors apply the cost—benefit framework to study perceptions of decision strategies for samples of university students from the People's Republic of China and the United States. The results show cross-cultural differences in the perceptions. Noncompensatory strategies, especially the lexicographic strategy, are perceived more favorably by the Chinese than by the Americans. Strategies using attribute weights are perceived important by the Chinese, more so than by the Americans. Furthermore, the perceived efficient frontiers of the two cultures differ markedly.