bluuebunny/crossref_metadata_2025 huggingface dataset:
Sex-based transmural differences in cardiac repolarization and ionic-current properties in canine left ventricles
Authors: Xiao Ling , Zhang Liming , Han Wei , Wang Zhiguo , Nattel Stanley
Published: February 2006

The female sex is associated with longer electrocardiographic QT intervals and increased proarrhythmic risks of QT-prolonging drugs. This study examined the hypothesis that sex differences in repolarization may be associated with differential transmural ion-current distribution. Whole cell patch-clamp and current-clamp were used to study ionic currents and action potentials (APs) in isolated canine left ventricular cells from epicardium, midmyocardium, and endocardium. No sex differences in AP duration (APD) were found in cells from epicardium versus endocardium. In midmyocardium, APD was significantly longer in female dogs (e.g., at 1 Hz, female vs. male: 288 ± 21 vs. 237 ± 8 ms; P < 0.05), resulting in greater transmural APD heterogeneity in females. No sex differences in inward rectifier K+current ( IK1) were observed. Transient outward K+current ( Ito) densities in epicardium and midmyocardium also showed no sex differences. In endocardium, female dogs had significantly smaller Ito(e.g., at +30 mV, female vs. male: 2.5 ± 0.2 vs. 3.5 ± 0.3 pA/pF; P < 0.05). Rapid delayed-rectifier K+current ( IKr) density and activation voltage-dependence showed no sex differences. Female dogs had significantly larger slow delayed-rectifier K+current ( IKs) in epicardium and endocardium (e.g., at +40 mV; tail densities, female vs. male; epicardium: 1.3 ± 0.1 vs. 0.8 ± 0.1 pA/pF; P < 0.001; endocardium: 1.2 ± 0.1 vs. 0.7 ± 0.1 pA/pF; P < 0.05), but there were no sex differences in midmyocardial IKs. Female dogs had larger L-type Ca2+current ( ICa,L) densities in all layers than male dogs (e.g., at −20 mV, female vs. male, epicardium: −4.2 ± 0.4 vs. −3.2 ± 0.2 pA/pF; midmyocardium: −4.5 ± 0.5 vs. −3.3 ± 0.3 pA/pF; endocarium: −4.5 ± 0.4 vs. −3.2 ± 0.3 pA/pF; P < 0.05 for each). We conclude that there are sex-based transmural differences in ionic currents that may underlie sex differences in transmural cardiac repolarization.
Temperature modulates P2X receptor-mediated cardiovascular responses to muscle afferent activation
Authors: Gao Zhaohui , Kehoe Valerie , Xing Jihong , Sinoway Lawrence , Li Jianhua
Published: February 2006

Static muscle contraction increases ATP release into the muscle interstitial space. Elevated ATP in muscle stimulates thin fiber muscle afferents and increases blood pressure via engagement of purinergic P2X receptors. In addition, ATP activates P2X receptors and enhances cardiovascular responses induced by stimulation of muscle mechanoreceptors. In this study, we examined whether elevated muscle temperature would attenuate and whether reduced temperature would potentiate P2X effects on reflex muscle responses. α,β-Methylene ATP (α,β-MeATP) was injected into the arterial blood supply of hindlimb muscle to stimulate P2X receptors, and muscle stretch was induced to activate mechanically sensitive muscle afferents as α,β-MeATP was injected in 10 anesthetized cats. Femoral arterial injection of α,β-MeATP (1.0 mM) increased mean arterial pressure (MAP) by 35 ± 5 (35°C), 26 ± 3 (37°C), and 19 ± 3 mmHg (39°C; P < 0.05 vs. 35°C), respectively. Muscle stretch (2 kg) elevated MAP. The MAP response was significantly enhanced 34% and 36% when α,β-MeATP (0.2 mM) was arterially infused 5 min before muscle stretch at 35° and 37°C, respectively. However, as muscle temperature reached 39°C, the stretch-evoked response was augmented only 6% by α,β-MeATP injection, and the response was significantly attenuated compared with the response with muscle temperature of 35° and 37°C. In addition, we also examined effects of muscle temperature on α,β-MeATP enhancement of the cardiovascular responses to static muscle contraction while the muscles were freely perfused and the circulation to the muscles was occluded. Because muscle temperature was 37°C, arterial injections of α,β-MeATP significantly augmented contraction-evoked MAP response by 49% (freely perfused) and 53% (ischemic condition), respectively. It is noted that this effect was significantly attenuated at a muscle temperature of 39°C. These data indicate that the effect of P2X receptor on reflex muscle response is sensitive to alternations of muscle temperature and that elevated temperature attenuates the response.
Flecainide sensitivity of a Na channel long QT mutation shows an open-channel blocking mechanism for use-dependent block
Authors: Zhu Yujie , Kyle John W. , Lee Peter J.
Published: February 2006

A long QT mutation in the cardiac sodium channel, D1790G (DG), shows enhanced flecainide use-dependent block (UDB). The relative importance of open and inactivated states of the channel in flecainide UDB has been controversial. We used a modifiable, inactivation-deficient mutant channel that contains the F1486C mutation in the IFM motif to investigate the UDB difference between the wild-type (WT-ICM) and DG (DG-ICM) channels. UDB at 5 Hz was greater in DG-ICM than WT-ICM, and IC50 values for steady-state UDB were 7.19 and 18.06 μM, respectively. When [2-(trimethyammonium) ethyl]methanethiosulfonate bromide (MTSET) was included in the pipette and fast inactivation was disabled, IC50 was 5.04 μM for DG-ICM and 12.63 μM for WT-ICM. We measured open-channel block by flecainide directly in MTSET-treated, noninactivating ICM channels. Steady-state block was higher for DG-ICM than WT-ICM (IC50 was 2.34 μM for DG-ICM and 5.87 μM for WT-ICM), suggesting that open-channel block is an important determinant of flecainide UDB. We obtained association ( kon) and dissociation ( koff) rates for open-channel block by the Langmuir-isotherm model. They were koff = 31.37 s−1, kon = 5.83 s−1·μM−1, and calculated Kd = 5.38 μM for WT-ICM (where Kd = koff/ kon); and koff = 24.88 s−1, kon = 9.54 s−1·μM−1, and calculated Kd = 2.61 μM for DG-ICM. These Kd values were similar to IC50 measured from steady-state open-channel block. Furthermore, we modeled UDB mathematically by using these kinetic rates and found that the model predicted experimental UDB accurately. The recovery from UDB had a minor contribution to UDB. Flecainide UDB is predominantly determined by an open-channel blocking mechanism, and DG-ICM channels appeared to have an altered open-channel state with higher flecainide affinity than WT-ICM.
Transvascular protein transport in mice lacking endothelial caveolae
Authors: Rosengren Bert-Inge , Rippe Anna , Rippe Catarina , Venturoli Daniele , Swärd Karl , Rippe Bengt
Published: February 2006

Caveolae are Ω-shaped vesicular structures postulated to play a role in transvascular protein transport. Studies on mice lacking endothelial caveolae, caveolin-1 knockout (Cav-1-KO) mice, indicate increased macromolecular transport rates. This was postulated to be due to the appearance of an alternative pathway. The present study tested whether an alternative pathway had appeared in Cav-1-KO mice. Male Cav-1-KO ( n = 12) and male control mice ( n = 13) were intubated and anesthetized using 2% isoflurane.125I-labeled albumin,131I-labeled immunoglobulin M (IgM), and polydisperse FITC-Ficoll were administered intravenously. During tracer administration, a 90-min peritoneal dialysis dwell was performed. Clearance of tracers to dialysate and permeability-surface area product for glucose were assessed. Transvascular protein transport was higher in Cav-1-KO compared with control mice. Albumin clearance from plasma to peritoneum was 0.088 ± 0.008 μl/min in control and 0.179 ± 0.012 μl/min in Cav-1-KO ( P = 0.001) mice. IgM clearance was 0.049 ± 0.003 and 0.083 ± 0.010 μl/min in control and Cav-1-KO mice, respectively ( P = 0.016). Ficoll clearance was increased in Cav-1-KO mice. In conclusion, the lack of caveolae in Cav-1-KO mice resulted in a marked increase in macromolecular transport. A two-pore analysis of the Ficoll clearance data revealed that the higher transport rate in Cav-1-KO mice was not compatible with the appearance of an alternative pathway for macromolecular transport. In contrast, the higher transperitoneal protein and Ficoll clearance is consistent with passive porous transport through an unperturbed two-pore system, presumably at an elevated capillary hydraulic pressure. Alternatively, the data may be explained by reductions in the selectivity of the endothelial glycocalyx, leading to an increased capillary hydraulic conductivity and large solute filtration.
Eicosapentaenoic acid prevents endothelin-1-induced cardiomyocyte hypertrophy in vitro through the suppression of TGF-β1 and phosphorylated JNK
Authors: Shimojo Nobutake , Jesmin Subrina , Zaedi Sohel , Maeda Seiji , Soma Masaaki , Aonuma Kazutaka , Yamaguchi Iwao , Miyauchi Takashi
Published: February 2006

The cardiovascular benefit of fish oil in humans and experimental animals has been reported. Endothelin (ET)-1 is a well-known cardiac hypertrophic factor. However, although many studies link a fish oil extract, eicosapentaenoic acid (EPA), to cardiac protection, the effects of EPA on cardiac hypertrophy and underlying mechanism(s) are unclear. The present study investigated whether EPA prevents ET-1-induced cardiomyocyte hypertrophy; the potential pathways likely to underlie such an effect were also investigated. Cardiomyocytes were isolated from neonatal rat heart, cultured for 3 days, and then treated for 24 h with vehicle only (control), treated with 0.1 nM ET-1 only, or pretreated with 10 μM EPA and then treated with 0.1 nM ET-1. The cells were harvested, and changes in cell surface area, protein synthesis, expression of a cytoskeletal (α-actinin) protein, and cell signaling were analyzed. ET-1 induced a 97% increase in cardiomyocyte surface area, a 72% increase in protein synthesis rate, and an increase in expression of α-actinin and signaling molecule [transforming growth factor-β1 (TGF-β1), c-Jun NH2-terminal kinase (JNK), and c-Jun]. Development of these ET-1-induced cellular changes was attenuated by EPA. Moreover, the hypertrophied cardiomyocytes showed a 1.5- and a 1.7-fold increase in mRNA expression of atrial and brain natriuretic peptides, the classical molecular markers of cardiac hypertrophy, respectively; these changes were also suppressed by EPA. Here we show that ET-1 induces cardiomyocyte hypertrophy and expression of hypertrophic markers, possibly mediated by JNK and TGF-β1 signaling pathways. These ET-1-induced effects were blocked by EPA, a major fish oil ingredient, suggesting that fish oil may have beneficial protective effects on cardiac hypertrophy.
Coronary flow reserve and heart failure in experimental coxsackievirus myocarditis. A transthoracic Doppler echocardiography study
Authors: Saraste Antti , Kytö Ville , Saraste Markku , Vuorinen Tytti , Hartiala Jaakko , Saukko Pekka
Published: February 2006

The objective of this study was to apply transthoracic Doppler echocardiography (TTDE) in mice to study coronary flow reserve (CFR), an index of coronary microvascular function, in mild and severe forms of experimental viral myocarditis. Regarding methodology, BALB/c mice were infected with cardiotropic coxsackieviruses causing either a mild (Nancy strain) or a severe (Woodruff strain) myocarditis. Left ventricular dimensions, fractional shortening, and CFR (ratio of left coronary artery flow velocity during maximal adenosine-induced vasodilatation to rest) were measured by TTDE before infection and again 1 or 2 wk after infection. As a result, the resting flow velocity did not change after infection. In contrast, CFR reduced significantly 1 wk after infection with either virus variant [from 2.5 (SD 0.3) to 1.4 (SD 0.1) in severe and from 2.4 (SD 0.4) to 2.1 (SD 0.3) in mild myocarditis], being significantly lower in the severe than mild myocarditis. CFR remained low in severe myocarditis 2 wk after infection. Fractional shortening decreased to the same levels 1 wk after infection with either virus variant [from 0.54 (SD 0.02) to 0.43 (SD 0.03) in severe and from 0.51 (SD 0.03) to 0.44 (SD 0.02) in mild myocarditis, P < 0.05]. However, 2 wk after infection, mice with severe myocarditis had enlarged left ventricles and lower fractional shortening [0.31 (SD 0.03)] than mice with mild myocarditis [0.47 (SD 0.02), P < 0.01]. In conclusion, CFR measured with TTDE is reduced in coxsackievirus myocarditis in mice. Low CFR is associated with progressive heart failure, indicating that dysfunction of coronary microcirculation is a determinant of poor outcome in viral myocarditis.
Neither SP-A nor NH2-terminal domains of SP-A can substitute for SP-D in regulation of alveolar homeostasis
Authors: Zhang Liqian , Ikegami Machiko , Korfhagen Thomas R. , McCormack Francis X. , Yoshida Mitsuhiro , Senior Robert M. , Shipley J. Michael , Shapiro Steven D. , Whitsett Jeffrey A.
Published: February 2006

Surfactant proteins (SP)-A and -D are members of the collectin family of host defense proteins that share four distinct structural domains: NH2-terminal oligomerization, collagenous, neck, and carbohydrate recognition (CRD). To determine the specificity of the functions of these domains, the SFTPC promoter was used to express 1) full-length rat (r) Sftpa; 2) NH2- rSftpa/d, consisting of NH2-terminal and collagenous domains of SP-A with neck domain and CRD of SP-D; and 3) rSftpd/a, consisting of NH2-terminal and collagenous domains of SP-D with neck domain and CRD of SP-A, in Sftpd−/−mice. Increased expression of SP-A in Sftpd−/−mice did not correct the increased pulmonary saturated phosphatidylcholine levels, emphysema, or foamy alveolar macrophage and lymphocyte infiltrations characteristic of Sftpd−/−mice, indicating that the decreased SP-A level noted in Sftpd−/−mice does not account for the observed pulmonary abnormalities. The chimeric protein NH2-rSftpa/d was expressed and detected in the airways of transgenic mice, migrating as an SP-A-like oligomer that associated with large aggregate surfactant in a manner similar to that of SP-A rather than SP-D. NH2-rSftpa/d did not correct emphysema, foamy macrophage and lymphocyte infiltration, or the increased lipid accumulations characteristic of Sftpd−/−mice. Thus oligomerization and surfactant lipid association of SP-D requires its NH2-terminal and collagenous domains, which are needed for SP-D-dependent regulation of surfactant homeostasis in vivo. Attempts to express rSftpd/a fusion protein in vivo were unsuccessful. Mmp9−/−/Sftpd−/−and Mmp12−/−/Sftpd−/−mice developed air space enlargement similar to Sftpd−/−mice, supporting the concept that the increased expression of each metalloproteinase seen in Sftpd−/−lungs is not the major cause of emphysema.
Persistent mucus accumulation: a consequence of delayed bronchial mucous cell apoptosis in RAO-affected horses?
Authors: Bartner Lisa R. , Robinson N. Edward , Kiupel Matti , Tesfaigzi Yohannes
Published: February 2006

This study examined the contribution of delayed apoptosis of bronchial mucous cells to mucus accumulation in equine recurrent airway obstruction (RAO). In pilot studies, Bcl-2, an apoptosis inhibitor, was detected in airway mucous cells of RAO-affected horses in remission and during acute disease, when most mucus was secreted. To study whether delayed apoptosis results in an increase in the number of mucous cells during disease recovery, six RAO-affected and six control horses were fed hay for 5 days to induce inflammation and then pellets for 7 days to partially resolve RAO before euthanasia. RAO-affected horses had more airway obstruction and luminal mucus than control horses under both management systems. At the time of euthanasia, RAO-affected horses had more inflammation and Bcl-2-positive bronchial mucous cells than control animals. In horses with >10 and <10 neutrophils per microliter of bronchoalveolar lavage fluid, >50% and <10% of mucous cells stained positive for Bcl-2, respectively. No differences in mucous cell number or amount of stored mucosubstance were observed between RAO-affected and control horses, but in RAO-affected animals, the amount of stored mucosubstance decreased as the number of neutrophils in bronchoalveolar lavage fluid increased. Because the number of mucous cells was similar in both groups of horses but only mucous cells of RAO-affected horses expressed Bcl-2 during recovery from acute disease, a conclusive role for Bcl-2 in prolonging bronchial mucous cell life could not be determined. Future studies are needed to compare horses that are kept in remission for prolonged periods when all mucous cells are fully developed.
Dietary isoflavone supplementation modulates lipid metabolism via PPARα-dependent and -independent mechanisms
Authors: Mezei Orsolya , Li Yilan , Mullen Eimear , Ross-Viola Jennifer S. , Shay Neil F.
Published: March 2006

Intake of soy protein has been associated with improvements in lipid metabolism, with much attention being focused on the serum cholesterol-lowering property of soy. The component or components of soy that are responsible for improvements in lipid metabolism have been investigated and their specific actions debated. One component, the isoflavones, has been shown to have weak estrogenic activity, and recently, several research groups have suggested that isoflavones are activating peroxisome proliferator-activated receptors (PPARs). The three different isoforms of PPARs (α, γ, and δ) have overlapping tissue distributions and functions associated with lipid metabolism. The goal of the present study was to investigate the hypothesis that the effect of isoflavones is mediated through the PPARα receptor. Male and female 129/Sv mice were obtained, including both wild-type and genetically altered PPARα knockout mice. Groups of mice were fed high-fat atherogenic diets containing soy protein +/- isoflavones and PPARα agonist fenofibrate for 6 wk. At the end of 6 wk, serum and tissue lipid levels were measured along with hepatic gene expression. Most notably, serum triglycerides were reduced by isoflavone consumption. Compared with intake of a low-isoflavone basal diet, isoflavone intake reduced serum triglyceride levels by 36 and 52% in female and male wild-type mice, respectively, compared with 55 and 52% in fenofibrate-treated mice. Isoflavones also improved serum triglyceride levels in knockout mice, whereas fenofibrate did not, suggesting that two different regulatory mechanisms may be affected by isoflavone intake. Isoflavone intake resembled action of fenofibrate on PPARα-regulated gene expression, although less robustly compared with fenofibrate. We suggest that, at the levels consumed in this study, isoflavone intake is altering lipid metabolism in a manner consistent with activation of PPARα and also via a PPARα-independent mechanism as well.
CADASIL: A Critical Look at a Notch Disease
Authors: Louvi Angeliki , Arboleda-Velasquez Joseph F. , Artavanis-Tsakonas Spyros
Published: March 2006

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a catastrophic late-onset syndrome which manifests itself mainly as a central nervous system degenerative disorder. CADASIL has been associated with mutations in the Notch 3 receptor which appear to cause, mainly, vascular abnormalities. Although more than a decade has passed since Notch 3 mutations were linked with this disease, we still do not have a good grasp on the molecular mechanisms underlying the CADASIL-associated Notch 3 receptor malfunction, nor do we understand many aspects of the CADASIL pathobiology. In this review, we discuss the CADASIL-related literature and attempt to evaluate the various experimental systems and approaches used to address what seems to be a paradigm for studying the pathobiology and genetics of vascular cognitive impairment.
Effect of Aging on the Expression of Peroxisome Proliferator-Activated Receptor γ and the Possible Relation to Insulin Resistance
Authors: Ye Ping , Zhang Xiu-jin , Wang Zhao-jun , Zhang Cheng
Published: March 2006

Background: The morbidity of insulin resistance tends to increase with aging. However, studies on molecular mechanisms underlying insulin resistance in aging process is still in paucity. Objective: The effect of aging on peroxisome proliferator-activated receptor γ (PPARγ) expression, and in addition, the possible association of PPARγ expression with insulin resistance in aging processwere investigated. Methods: The minimal model technique (MMT) based on frequently sampled intravenous glucose tolerance test was adopted and SI and glucose effectiveness of young and aged rats were compared. RT-PCR and Western blot were used to determine the expression of PPARγ at mRNA and protein level in adipose tissue and skeletal muscle, as well as in human colic omentum, respectively. Results: MMT result implied existence of various degrees of insulin resistance in aged rats. The expression of PPARγ at both mRNA and protein levels in adipose tissue of aged rats dramatically decreased; consequently, the expression of its target gene lipoprotein lipases mRNA also markedly decreased compared with those in young rats. Furthermore, the level of PPARγ mRNA and glucose transporter-4 mRNA in skeletal muscle of aged rats attenuated significantly. The expression of PPARγ mRNA in omental adipose tissue of old men was significantly decreased, accompanied by a tendency of higher insulin resistance index, compared with those of the young. Conclusion: Aging may be associated with diminished PPARγ expression affecting insulin resistance in the aged individuals.
Underappreciated Predictors for Postdischarge Mortality in Acute Hospitalized Oldest-Old Patients
Authors: Iwata Mitsunaga , Kuzuya Masafumi , Kitagawa Yoshimi , Suzuki Yusuke , Iguchi Akihisa
Published: March 2006

Background: Although oldest-old, those aged 85 years and older, patients are the fastest growing segment, clinical evidences regarding the acute care of oldest-old patients are still lacking. Because acute medical conditions requiring emergent hospitalization is frequently followed by high rate of progressive physical decline and increased mortality after discharge in oldest-old patients, prognostic information collected during hospitalization can provide the basis for discussion about the goals of care and therapy. The aim of our study was to identify predictive factors for postdischarge mortality in oldest-old patients. Methods: The study included 403 oldest-old patients discharged from the acute care setting of a general hospital, who were followed-up for 1 year. Predictive values of the patients’ characteristics collected during their hospitalization for 1-year mortality were identified utilizing Cox proportional hazard regression analysis. Results: During 1-year follow-up, 104 patients (25.8%) died. The variables independently associated with 1-year mortality in multivariate analysis were the Charlson Comorbidity Index equal or greater than 2 [HR (hazard ratio) 4.71, 95%CI (confidence interval) 1.09–20.42], six or more prescribed medications at discharge (HR 3.12, 95% CI 1.39–6.99), benzodiazepines use (HR 1.64, 95% CI 1.04–2.60), nonsteroidal anti-inflammatory drugs use (HR 1.70, 95% CI 1.10–2.63), albumin less than or equaling 3.4 g/dl (HR 2.16, 95% CI 1.13–4.14), hemoglobin 10–12 g/dl (HR 2.32, 95% CI 1.22–3.56), hemoglobin less than 10 g/dl (HR 2.67, 95% CI 1.43–4.95), the presence of pressure sores (HR 1.84, 95% CI 1.14–2.97), and a history of delirium (HR 2.24, 95% CI 1.32–3.79). Functional impairment assessed by the Katz Index was only weakly associated with mortality (HR 1.24, 95% CI 0.53–2.91). Conclusion: Although often underappreciated, polypharmacy, particular medication use, anemia, the presence of pressure sores, and a history of delirium were important predictors for postdischarge mortality in oldest-old patients.
Imaging Artificial Caries on the Occlusal Surfaces with Polarization-Sensitive Optical Coherence Tomography
Authors: Jones R.S. , Darling C.L. , Featherstone J.D.B. , Fried D.
Published: March 2006

Polarization-sensitive optical coherence tomography (PS-OCT) is a nondestructive imaging system that can utilize near-infrared (IR) light to produce depth-resolved images of dental enamel and has the potential to monitor early enamel occlusal caries. The objective of this study was to investigate the relationship between the magnitude of backscattered light and depolarization recorded by PS-OCT with changes in the enamel mineral volume in an artificial caries model. Artificial lesions were created on a selected region on the occlusal surfaces of sound posterior teeth (n = 10) using a well-characterized 14-day pH cycling model. An all-fiber-based PS-OCT system operating at 1,310 nm was used to collect serial images at day 0 and day 14 prior to tooth sectioning. The quantitative mineral content profile and relative mineral loss, ΔZ (%vol × µm), of the carious enamel samples were obtained from transverse sections using high-resolution digital microradiography (DM). Line profiles of PS-OCT and DM images were used to evaluate the artificial caries severity and depth. The integrated reflectivity of the perpendicular-axis PS-OCT image, quantifying lesion severity, was correlated to the ΔZ of the caries lesions. There was also a strong correlation between the lesion depth calculated from both imaging modalities. PS-OCT can image and quantify artificial occlusal caries by measuring the increase in backscattering and depolarization of near-IR light. This optical method has promising applications for in vivo detection and monitoring of early enamel occlusal caries.
Exploratory Study of Some Acoustic and Articulatory Characteristics of Sad Speech
Authors: Erickson Donna , Yoshida Kenji , Menezes Caroline , Fujino Akinori , Mochida Takemi , Shibuya Yoshiho
Published: March 2006

This study examines acoustic and articulatory EMA data of two female speakers(American and Japanese) spontaneously producing emotional speech whileengaged in an informal telephone-type conversation. A set of control data inwhich the speakers imitated or read the original emotional utterance was alsorecorded; for the American speaker, the intonation pattern was also imitated. Theresults suggest (1) acoustic and articulatory characteristics of spontaneous sadspeech differ from that of read speech or imitated intonation speech, (2) spontaneoussad speech and imitated sad speech seem to have similar acoustic characteristics(high F0, changed F1 as well as voice quality), but articulation is different interms of lip, jaw and tongue positions, and (3) speech that is rated highly by listenersas sad is associated with high F0 and changed voice quality.
No Compensatory Upregulation of Placental Dimethylarginine Dimethylaminohydrolase Activity in Preeclampsia
Authors: Siroen Michiel P.C. , Teerlink Tom , Bolte Antoinette C. , van Elburg Ruurd M. , Richir Milan C. , Nijveldt Robert J. , van der Hoven Ben , van Leeuwen Paul A.M.
Published: March 2006

Background/Aims: Placental dysfunction of the asymmetric dimethylarginine (ADMA) degrading enzyme dimethylarginine dimethylaminohydrolase (DDAH) has been suggested as one of the initiating events in the development of preeclampsia (PE). Our primary aim was to investigate the role of the placenta in the metabolism of ADMA during normal pregnancy and PE. Methods: We studied 27 nonpregnant healthy women (C), 15 normotensive pregnant females (P), 16 patients with PE, and 7 patients with the ‘hemolysis, elevated liver enzymes and low platelets’ syndrome (H). Results: There were no significant differences between P and PE with respect to fetomaternal gradient of ADMA, placental DDAH activity and placental ADMA content. During the first stage of labour, mean (±SD) plasma ADMA (μmol/l) was higher in H (0.69 ± 0.22; p < 0.05) compared with C (0.44 ± 0.07), P (0.37 ± 0.06), and PE (0.40 ± 0.06). ADMA was significantly associated with laboratory parameters of hepatic and renal function and with clinical parameters, including systolic and diastolic blood pressure, gestational age, birth weight, and placenta weight. Conclusions: A compensatory upregulation of placental DDAH activity is absent in patients suffering from PE and levels of ADMA in plasma and placenta are normal in patients suffering from PE. However, when the course of PE deteriorates and organ dysfunction (especially liver and kidney) becomes involved, such as during the hemolysis, elevated liver enzymes and low platelets syndrome, ADMA levels increase.
Successful Outcome of Twin Gestation after Endoscopic Metroplasty of Complete Septate Uterus
Authors: Jakiel G. , Robak-Cholubek D.
Published: March 2006

The successful outcome of twin gestation after the endoscopic metroplasty of uterus septus class Va was described. Authors described and discussed the technical details of diagnosis and treatment of this rare malformation. Five months after treatment the patient spontaneously became pregnant. The pregnancy was determined as dizygotic twins. The cesarean section was performed in the 36th week of gestation because of growth arrest of one fetus and two healthy newborns were delivered.
Psychosocial Factors Associated with Knowledge about Affective Disorders in Patients with Depression
Authors: Kronmüller Klaus-Thomas , Saha Rina , Karr Markus , Kratz Benita , Hunt Aoife , Mundt Christoph , Backenstrass Matthias
Published: March 2006

Background: Increasing importance is attributed to the knowledge that patients have concerning their illness. For psychiatric disorders, imparting information about the illness has become a standard part of treatment. Despite the great clinical relevance of knowledge about depression, only few empirical studies on this subject have been carried out. This study aimed to identify psychosocial factors associated with greater or lesser knowledge about affective disorders. Methods: Sixty-one in-patients with depression were recruited and tested with the Knowledge about Depression and Mania Inventory. Results: Almost all patients sought specific information about their disorder prior to admission to hospital. There were large differences in patients’ knowledge about the disorder and their choice of information source. Older and less educated patients had less knowledge about affective disorders. Patients with less illness knowledge also have a less favourable illness concept, poorer interpersonal relationships and more passive coping strategies. Conclusions: The results show that knowledge about affective disorders is a central illness characteristic that has numerous implications for the ability to cope with the disorder, as well as for psychotherapeutic management. The results contribute to a clarification of the relationship between psychoeducation and psychotherapy.
The Discriminatory Value of the Low-Dose Dexamethasone Suppression Test in the Investigation of Paediatric Cushing’s Syndrome
Authors: Dias R. , Storr H.L. , Perry L.A. , Isidori A.M. , Grossman A.B. , Savage M.O.
Published: March 2006

Background: Low- and high-dose dexamethasone suppression tests (LDDST, HDDST) are used in the investigation of Cushing’s syndrome (CS). In adults with Cushing’s disease (CD), cortisol suppression during LDDST predicts suppression during the HDDST. Methods: We reviewed the results of the LDDST (0.5 mg 6 hourly × 48 h), HDDST (2.0 mg 6 hourly × 48 h) and corticotrophin-releasing hormone (CRH) test in 32 paediatric patients with CS: 24 had CD, 1 ectopic ACTH syndrome, 5 nodular adrenal hyperplasia and 2 adrenocortical tumours. Results: In CD, LDDST suppressed cortisol from 590.7 ± 168.8 (mean ± SD) to 333.7 ± 104.0 nmol/l after 48 h (0 vs. 48 h, p < 0.05; mean suppression, 45.1%; CI (30.8, 59.4%); 16/24 (66%) suppressed >30%; mean suppression 68.1%, CI (58.1, 77.9%)). The HDDST suppressed cortisol from 596.3 ± 174.5 to 47.1 ± 94.8 nmol/l after 48 h (0 vs. 48 h, p < 0.05; mean suppression, 93.5%; CI (88.2, 98.8%) with 17/24 (71%) suppressing to <50 nmol/l and 100% to <50% of baseline). In the LDDST, suppression correlated with that during the HDDST (r = +0.45, p < 0.05) with >30% suppression predicting that in the HDDST and hence CD. CRH increased cortisol by +100.3% (CI 62, 138.5%), 22/24 (91.7%) showing a >20% increase. In the other CS pathologies (n = 8) the LDDST induced no significant decrease in cortisol. Conclusion: The LDDST was of diagnostic value by discriminating between CD and other CS aetiologies. In our view the HDDST is redundant in the investigation of paediatric CS.
Endothelial Dysfunction and Low-Grade Inflammation Explain Much of the Excess Cardiovascular Mortality in Individuals With Type 2 Diabetes
Authors: de Jager Jolien , Dekker Jacqueline M. , Kooy Adriaan , Kostense Piet J. , Nijpels Giel , Heine Rob J. , Bouter Lex M. , Stehouwer Coen D.A.
Published: March 2006

Objective—

The mechanisms responsible for the increased cardiovascular disease risk that accompanies type 2 diabetes (T2D) remain poorly understood. It is commonly held that endothelial dysfunction and low-grade inflammation can explain, at least in part, why deteriorating glucose tolerance is associated with cardiovascular disease. However, there is no direct evidence for this contention.

Methods and Results—

In this population-based study (n=631), T2D was cross-sectionally associated with both endothelial dysfunction and low-grade inflammation, whereas impaired glucose metabolism (IGM) was associated only with low-grade inflammation. These findings were independent of other risk factors that accompany T2D or IGM. During a follow-up of 11.7 years (median; range 0.5 to 13.2 years), low-grade inflammation was associated with a greater risk of cardiovascular mortality (hazard ratio, 1.43 [95% CI, 1.17 to 1.77] per 1 SD difference). For endothelial dysfunction, the association with cardiovascular mortality was stronger in diabetic (hazard ratio, 1.87 [95% CI, 1.43 to 2.45]) than in nondiabetic individuals (hazard ratio, 1.23 [95% CI, 0.86 to 1.75];
P
interaction=0.06). Finally, T2D-associated endothelial dysfunction and low-grade inflammation explained ≈43% of the increase in cardiovascular mortality risk conferred by T2D.

Conclusions—

These data emphasize the necessity of randomized controlled trials of strategies that aim to decrease cardiovascular disease risk by improving endothelial function and decreasing low-grade inflammation, especially for T2D patients.
Predicting Mortality in Spontaneous Intracerebral Hemorrhage
Authors: Godoy Daniel Agustin , Piñero Gustavo , Di Napoli Mario
Published: March 2006

Background and Purpose—A clinical grading scale for intracerebral hemorrhage (ICH), formally ICH score, was recently developed showing to predict 30-day mortality in a simple and reliable manner. The aim of the present study was to validate the original ICH (oICH) score in an independent cohort of patients from a developing country assessing 30-day mortality and 6-month functional outcome and whether its modifications can improve prediction.

Methods—Consecutive patients admitted with acute ICH between January 1, 2003, and July 31, 2004, were prospectively included. oICH score was applied and 2 modified ICH (mICH) scores were created with the same variables, except localization, of the oICH score but with different cutoff values. Outcome was assessed as 30-day mortality and 6-month good outcome (Glasgow Outcome Scale [GOS] 4 to 5).

Results—A total of 153 patients were included during study period. Thirty-day mortality rate was 34.6% (n=53), and 59 patients (38.6%) had good functional outcome (GOS 4 to 5) at 6 months. The oICH and mICH scores predicted mortality equally well. According to Youden’s index (J), the oICH score was a reliable predictor for mortality (J=0.59) but less reliable for predicting good outcome (J=0.54). The mICH scores were equal in predicting mortality but better for predicting good outcome than the oICH score (J=0.60).

Conclusions—oICH score also confirms its validity in a socially and culturally different population. Modifications of oICH do not improve its 30-day mortality prediction but improve its ability to predict good functional outcome at 6 months.
Postmortem Examination of Vascular Lesions in Cognitive Impairment
Authors: Pantoni Leonardo , Sarti Cristina , Alafuzoff Irina , Jellinger Kurt , Munoz David G. , Ogata Jun , Palumbo Vanessa
Published: March 2006

Background and Purpose—

A full appreciation of the presence of cerebral vascular lesions in cognitively impaired patients can be ultimately reached at the neuropathological level. However, there are no detailed guidelines regarding what neuropathologists should look for at autopsy in cases of suspected vascular dementia or vascular cognitive impairment. We aimed at surveying the postmortem neuropathological procedures used in different centers in examining brain lesions of presumable or possible vascular origin in cognitively impaired patients.

Methods—

Thirteen laboratories participated in the survey by filling in a semistructured questionnaire. We reviewed sampling and histology procedures in use and the neuropathological definitions of some of these lesions. Neuropathological criteria for the definition of a vascular origin of the dementing process were also surveyed.

Results—

A large variability across centers was observed in the procedures used for the neuropathological examination and the histology techniques. Heterogeneity existed also in the definition of commonly found lesions (eg, white matter alterations, small vessel disease), interpretation of whether or not the lesions were reputed to be of vascular origin, and consequently in the interpretation of the cause of cognitive decline.

Conclusions—

The appreciation of the presence of neuropathologically verified vascular lesions in cognitively impaired cases may be heavily influenced by the laboratory tools used and also by the heterogeneity of the criteria applied in different centers. Harmonization of neuropathological procedures is badly needed in the field of vascular dementia and vascular cognitive impairment to better understand the association between various vascular lesions and clinical symptoms such as cognitive impairment.
Influence of Metabolic Syndrome and General Obesity on the Risk of Ischemic Stroke
Authors: Chen Hsin-Jen , Bai Chyi-Huey , Yeh Wen-Ting , Chiu Hou-Chang , Pan Wen-Harn
Published: March 2006

Background and Purpose—

In 2005, the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) guideline lowered the fasting glucose cut point used to define metabolic syndrome (MS). This study investigated the influence of MS on ischemic stroke (IS) risk using both the original and revised definitions. In addition, because abdominal obesity is the measure of obesity used in the guideline to define MS, we also investigated whether general obesity (GOB) should be considered in the definition of MS.

Methods—

Baseline data from 3453 adults (≥20 years of age) in the Cardiovascular Diseases Risk Factor Two-Township Study were linked to insurance claim and death certificate records. The 2001 and 2005 NCEP-ATP III definitions were used with Asian and Taiwanese specific cut-off values for waist circumference and body mass index. Hazard ratios of MS and GOB on IS were calculated using Cox models, and the Kaplan–Meier method was used to derive free-of-IS survival curves.

Results—

During 10.4 years of follow-up, 132 persons developed IS. Hazard ratios of subjects with 1 to 2 and ≥3 MS component disorders were 2.69 and 4.30, respectively, under the 2001 definition, and 3.16 and 5.15, respectively, under the 2005 definition (all
P
values <0.05). MS subjects with GOB had reduced survival at a borderline significance level. Adding GOB in the MS definition did not significantly alter the number of subjects with MS nor the ability to predict stroke risk. Replacing abdominal obesity with GOB in MS definition reduced the number slightly and increased the hazard ratio.

Conclusion—

MS predicted IS and the 2005 NCEP definition showed a stronger dose-response relationship with IS. Adding GOB to the existing MS definition had limited benefit.
Endosaccular Treatment of Intracranial Aneurysms Using Matrix Coils
Authors: Niimi Yasunari , Song Joon , Madrid Mary , Berenstein Alejandro
Published: March 2006

Background and Purpose—

The authors report their experience using Matrix coils in the treatment of cerebral aneurysms.

Methods—

The outcomes of 72 consecutive patients (76 aneurysms) who underwent coiling using Matrix coils at our institution were retrospectively analyzed.

Results—

Seventy-four aneurysms in 70 patients were coiled using Matrix coils (ranging 3% to 100% by coil length; mean 68.8%). Two patients underwent regular platinum coil embolization after failed Matrix coil placement. Thirty-two (42%) ruptured aneurysms were acutely treated. In 46 aneurysms, Matrix composed >50% of coil length. Complete aneurysm occlusion was obtained in 13 aneurysms (17.6%), neck remnant in 30 (40.5%), and dome filling in 31 (41.9%). Procedural morbidity and mortality rates were 1.4% and 1.4%, respectively. Angiographic follow-up was obtained in 63.5% (47 of 74 aneurysms; average 12.2 months; range 0 to 34). In these 47 angiographically followed aneurysms, the overall recanalization rate was 57.4%. In aneurysms with >50% Matrix coils, 76.1% had angiographic follow-up (35 of 46), and in this group, the overall recanalization rate was 54.3% (19 of 35): 25% (1 of 4) for very small (<5 mm); 33% (4 of 12) for small-size (<10 mm)/small-neck (<4 mm); and 63% (5 of 8) for small-size/wide-neck (≥4 mm). A total of 82% (9 of 11) recanalization occurred in large aneurysms (≥10 to 25 mm). Ten aneurysms (21.3%; 10 of 47) underwent retreatment. Clinical follow-up was obtained in 61 (86%) patients (average 15 months; range 1 to 37): 87% of patients were Glasgow Outcome Scale 4 or 5.

Conclusion—

The use of Matrix coils resulted in worse recanalization rates than that reported for Guglielmi detachable bare platinum coils.
Perfusion-CT Assessment of Infarct Core and Penumbra
Authors: Wintermark Max , Flanders Adam E. , Velthuis Birgitta , Meuli Reto , van Leeuwen Maarten , Goldsher Dorit , Pineda Carissa , Serena Joaquin , Schaaf Irene van der , Waaijer Annet , Anderson James , Nesbit Gary , Gabriely Igal , Medina Victoria , Quiles Ana , Pohlman Scott , Quist Marcel , Schnyder Pierre , Bogousslavsky Julien , Dillon William P. , Pedraza Salvador
Published: March 2006

Background and Purpose—

Different definitions have been proposed to define the ischemic penumbra from perfusion-CT (PCT) data, based on parameters and thresholds tested only in small pilot studies. The purpose of this study was to perform a systematic evaluation of all PCT parameters (cerebral blood flow, volume [CBV], mean transit time [MTT], time-to-peak) in a large series of acute stroke patients, to determine which (combination of) parameters most accurately predicts infarct and penumbra.

Methods—

One hundred and thirty patients with symptoms suggesting hemispheric stroke ≤12 hours from onset were enrolled in a prospective multicenter trial. They all underwent admission PCT and follow-up diffusion-weighted imaging/fluid-attenuated inversion recovery (DWI/FLAIR); 25 patients also underwent admission DWI/FLAIR. PCT maps were assessed for absolute and relative reduced CBV, reduced cerebral blood flow, increased MTT, and increased time-to-peak. Receiver-operating characteristic curve analysis was performed to determine the most accurate PCT parameter, and the optimal threshold for each parameter, using DWI/FLAIR as the gold standard.

Results—

The PCT parameter that most accurately describes the tissue at risk of infarction in case of persistent arterial occlusion is the relative MTT (area under the curve=0.962), with an optimal threshold of 145%. The PCT parameter that most accurately describes the infarct core on admission is the absolute CBV (area under the curve=0.927), with an optimal threshold at 2.0 ml×100 g
−1
.

Conclusion—

In a large series of 130 patients, the optimal approach to define the infarct and the penumbra is a combined approach using 2 PCT parameters: relative MTT and absolute CBV, with dedicated thresholds.
Impact of Great Salinity Anomalies on the Low-Frequency Variability of the North Atlantic Climate
Authors: Zhang Rong , Vallis Geoffrey K.
Published: March 2006

In this paper, it is shown that coherent large-scale low-frequency variabilities in the North Atlantic Ocean—that is, the variations of thermohaline circulation, deep western boundary current, northern recirculation gyre, and Gulf Stream path—are associated with high-latitude oceanic Great Salinity Anomaly events. In particular, a dipolar sea surface temperature anomaly (warming off the U.S. east coast and cooling south of Greenland) can be triggered by the Great Salinity Anomaly events several years in advance, thus providing a degree of long-term predictability to the system. Diagnosed phase relationships among an observed proxy for Great Salinity Anomaly events, the Labrador Sea sea surface temperature anomaly, and the North Atlantic Oscillation are also discussed.
Increased Occurrence of Stratospheric Sudden Warmings during El Niño as Simulated by WACCM
Authors: Taguchi Masakazu , Hartmann Dennis L.
Published: March 2006

Experiments with Whole Atmosphere Community Climate Model (WACCM) under perpetual January conditions indicate that stratospheric sudden warmings (SSWs) are twice as likely to occur in El Niño winters than in La Niña winters, in basic agreement with the limited observational dataset. Tropical SST anomalies that mimic El Niño and La Niña lead to changes in the shape of probability distribution functions (PDFs) of stratospheric day-to-day variability, resulting in a warmer pole and weaker vortex on average for El Niño conditions. The tropical SST forcing induces a response similar to the observed response in the enhancement of the planetary wave of zonal wavenumber 1 (wave 1) and the weakening of wave 2 in the upper troposphere and stratosphere of high latitudes. The enhanced wave 1 contributes to a shift of the PDFs of poleward eddy heat flux in the lower stratosphere, or wave forcing entering the stratosphere. The shift of the PDFs includes an increase of strong wave events that induce more frequent SSWs.
Violent Women
Authors: Pollock Joycelyn M. , Mullings Janet L. , Crouch Ben M.
Published: February 2006

Prior research on violent crime by female offenders is reviewed. A Texas female prisoner sample is used to explore specific questions raised by the literature review. Violent and nonviolent offenders were compared, looking specifically at race, socioeconomic status, having been raised in single-parent homes, criminal history, gang membership, marital status, and childhood abuse. Findings indicated that women who are violent were more likely to be younger, African American, unemployed, and having extensive criminal histories. They were more likely to come from dysfunctional families with childhood abuse. Limitations of the study were noted.
Taking Charge
Authors: David Wendy S. , Simpson Tracy L. , Cotton Ann J.
Published: February 2006

The authors describe an overview of the pilot project Taking Charge, a 36-hour comprehensive behavioral intervention involving psychoeducation, personal safety, and self-defense training for 12 female veterans with posttraumatic stress disorder (PTSD) from military sexual trauma. Self-defense training can incorporate the benefits of repeated exposure while teaching proactive cognitive and behavioral responses to the feared stimuli, and thus facilitate emotional and physical rescripting of and mastery over the trauma. Results up to 6 months follow-up indicate significant reductions in behavioral avoidance, PTSD hyperarousal, and depression, with significant increases in interpersonal, activity, and self-defense self-efficacy. The authors propose that this therapeutic self-defense curriculum provides an enhanced exposure therapy paradigm that may be a potent therapeutic tool in the treatment of PTSD.