bluuebunny/crossref_metadata_2025 huggingface dataset:
17β-Estradiol Increases Basal but Not Bradykinin-Stimulated Release of Active t-PA in Young Postmenopausal Women
Authors: Pretorius Mias , van Guilder Gary P. , Guzman Raul J. , Luther James M. , Brown Nancy J.
Published: February 2008

Angiotensin-converting enzyme inhibition potentiates basal and bradykinin-stimulated tissue-type plasminogen activator (t-PA) release to a greater extent in women than in men. This study tested the hypothesis that 17β-estradiol enhances the effect of angiotensin-converting enzyme inhibition on t-PA release in young postmenopausal women. We conducted a double-blind, prospective, crossover study in 14 young postmenopausal women (mean age 48.2±2.3 years) who were randomized to receive 17β-estradiol (1 mg/d) or matching placebo for 4 weeks. At the end of each treatment period, we measured the effect of intraarterial infusion of bradykinin, methacholine, and nitroprusside on forearm blood flow and net t-PA release, before and during intraarterial enalaprilat (0.33 μg/min/100 mL forearm volume). 17β-estradiol significantly reduced baseline venous plasminogen activator inhibitor-1 antigen (4.4±1.4 versus 10.4±2.5 ng/mL,
P
=0.001) and t-PA antigen (5.5±0.6 versus 7.5±1.3 ng/mL,
P
=0.022) compared with placebo. 17β-estradiol increased basal forearm vascular release of active t-PA compared with placebo (1.2±0.3 IU/mL/min versus 0.4±0.1 IU/mL/min respectively,
P
=0.032), without increasing t-PA antigen release (
P
=0.761). Enalaprilat significantly increased basal net t-PA antigen release (from −0.8±1.0 to 3.2±1.2 ng/min/100 mL,
P
=0.012), but not the release of active t-PA, during either placebo or 17β-estradiol. Enalaprilat potentiated bradykinin-stimulated vasodilation and t-PA antigen and activity release similarly during placebo and 17β-estradiol treatment. 17β-estradiol treatment does not alter the effect of angiotensin-converting enzyme inhibition on basal t-PA antigen or on bradykinin-stimulated t-PA antigen or activity release. 17β-estradiol increases basal release of active t-PA in young postmenopausal women, consistent with enhanced vascular fibrinolytic function.
Smoking in Moderate/Severe Preeclampsia Worsens Pregnancy Outcome, but Smoking Cessation Limits the Damage
Authors: Pipkin F. Broughton
Published: February 2008

We studied phenotypic and clinical outcome data in an observational, multicenter cohort study of 1001 Western European white women and their singleton babies, with stringently defined moderate-to-severe preeclampsia. Ninety women admitted to being current smokers; 71 had stopped smoking before entry to the study. Across the categories of never-smoker, stopped, and current smoker there were significant increases in the proportion of women delivering before 34 weeks’ gestation (
P
=0.011), delivering a baby below the third birth weight centile (
P
<0.001), or delivering a baby with any adverse outcome (
P
=0.011). By comparison with never-smokers, smoking during pregnancy was associated with a doubling of risk of being delivered before 34 weeks’ (odds ratio: 1.98; 95% CI: 1.24 to 3.16;
P
=0.004), of delivering babies below the third centile of corrected birth weight (odds ratio: 2.20; 95% CI 1.41 to 3.44;
P
<0.0001), or for their babies to have any adverse outcome (odds ratio: 1.87; 95% CI: 1.19 to 2.95;
P
<0.006). Worryingly, the risk of developing eclampsia was increased 5-fold (odds ratio: 4.88; 95% CI: 1.44 to 16.61;
P
=0.005). The proportion of smokers in these preeclamptic women was lower than in our pregnant population generally. However, preeclampsia still carries significant perinatal morbidity, and cigarette smoking in preeclamptic pregnancies exacerbates this. Stopping smoking decreases the risks. Smoking in young women should be a particular target for advice by general practitioners before pregnancy, with active encouragement after conception to enroll in such trials as the current Smoking, Nicotine and Pregnancy Trial to support cessation.
Low-Intensity Exercise Training Delays Heart Failure and Improves Survival in Female Hypertensive Heart Failure Rats
Authors: Chicco Adam J. , McCune Sylvia A. , Emter Craig A. , Sparagna Genevieve C. , Rees Meredith L. , Bolden David A. , Marshall Kurt D. , Murphy Robert C. , Moore Russell L.
Published: February 2008

Exercise training improves functional capacity and quality of life in patients with heart failure. However, the long-term effects of exercise on mortality associated with hypertensive heart disease have not been well defined. In the present study, we investigated the effect of low-intensity exercise training on disease progression and survival in female spontaneously hypertensive heart failure rats. Animals with severe hypertension (16 months old) were treadmill trained (14.5 m/min, 45 min/d, 3 d/wk) until they developed terminal heart failure or were euthanized because of age-related complications. Exercise delayed mortality resulting from heart failure (
P
<0.001) and all causes (
P
<0.05) and transiently attenuated the systolic hypertension and contractile dysfunction observed in the sedentary animals but had no effect on cardiac morphology or contractile function in end-stage heart failure. Training had no effect on terminal myocardial protein expression of antioxidant enzymes, calcium handling proteins, or myosin heavy chain isoforms but was associated with higher cytochrome oxidase activity in cardiac mitochondria (
P
<0.05) and a greater mitochondrial content of cardiolipin, a phospholipid that is essential for optimal mitochondrial energy metabolism. In conclusion, low-intensity exercise training significantly delays the onset of heart failure and improves survival in female hypertensive heart failure rats without eliciting sustained improvements in blood pressure, cardiac function, or expression of several myocardial proteins associated with the cardiovascular benefits of exercise. The effects of exercise on cytochrome oxidase and cardiolipin provide novel evidence that training may improve prognosis in hypertensive heart disease by preserving mitochondrial energy metabolism.
Hormonal and Volume Dysregulation in Women With Premenstrual Syndrome
Authors: Rosenfeld Rimma , Livne Dana , Nevo Ori , Dayan Lior , Milloul Victor , Lavi Shahar , Jacob Giris
Published: February 2008

Premenstrual syndrome (PMS) presents with emotional and physical symptoms. Although the emotional symptoms have been extensively studied, the pathophysiology of the fluid-retention symptoms is not currently known. We tested the hypothesis that the fluid regulatory mechanisms are disturbed in PMS. Nine regularly menstruating women with PMS were compared with 9 healthy age-matched women. Hemodynamic parameters and upright plasma volume shift (extrapolated from changes in hematocrit), plasma renin activity (PRA), and plasma aldosterone and sex hormones were measured at different times during the menstrual cycle. During the early follicular and the midluteal phases, the plasma volume shift, supine and upright PRA, and plasma aldosterone were similar in both groups, and none of the participants had edema. However, during the late luteal phase, ankle edema was present only in women with PMS, and their maximal plasma volume shift was lower compared with controls (11.7±1.3 versus 15.6±0.6;
P
=0.004). The area under the curve (estimates the amount of the total plasma shift during 30 minutes standing) was 300±28 and 406±16 in PMS and controls, respectively (
P
=0.01). PRA and aldosterone levels were higher during the late luteal phase in women with PMS compared with controls (supine PRA: 1.4±0.3 [PMS] versus 1.1±0.4 [control;
P
value not significant], upright PRA: 3.9±0.08 versus 1.6±0.3 ng/mL per hour [
P
=0.015], supine plasma aldosterone: 131±30 versus 68±17 pg/mL [
P
=0.09], and upright plasma aldosterone: 208±40 versus 102±16 pg/mL [
P
=0.03]). We, therefore, conclude that women with PMS have increased plasma fluid-regulatory hormones and disturbed fluid distribution only during their late luteal menstrual phase.
Chronic Tempol Prevents Hypertension, Proteinuria, and Poor Feto-Placental Outcomes in BPH/5 Mouse Model of Preeclampsia
Authors: Hoffmann Darren S. , Weydert Christine J. , Lazartigues Eric , Kutschke William J. , Kienzle Martha F. , Leach Jenny E. , Sharma Jennifer A. , Sharma Ram V. , Davisson Robin L.
Published: February 2008

Recently we described a mouse model, BPH/5, that spontaneously develops the hallmark clinical features of preeclampsia. BPH/5 exhibit impaired placentation before the onset of hypertension and proteinuria, supporting a causal role for the placenta in the pathogenesis of preeclampsia. Here we tested the hypothesis that an increase in reactive oxygen species (ROS) early in pregnancy results in placental abnormalities leading to the maternal symptoms of preeclampsia. We further hypothesized that chronic antioxidant therapy would ameliorate both feto-placental abnormalities and maternal symptoms. ROS levels measured by dihydroethidium revealed significant increases in oxidative stress in BPH/5 placentas at midgestation compared with C57 controls. This increase in ROS was correlated with reduced expression and activity of cytoplasmic superoxide dismutase in early and midgestation BPH/5 placentas. These abnormalities in placental oxidant factors occurred before the onset of maternal symptoms, suggesting a possible causal link between increased ROS and maternal and feto-placental pathology in this model. In support of this, chronic treatment of BPH/5 with the superoxide dismutase-mimetic Tempol throughout gestation significantly improved fetal growth and survival. Furthermore, Tempol ameliorated pregnancy-induced increases in blood pressure and proteinuria in BPH/5 mothers. We confirmed that Tempol radical was present in plasma, and it normalized ROS levels in all placental zones in BPH/5. These data for the first time demonstrate an important causative role for increased ROS in the placenta in the pathogenesis of preeclampsia in a model that spontaneously develops the disease. The results also strongly suggest the potential utility of antioxidant therapy in treating preeclampsia.
Hormonal Influences on Cardiovascular Norepinephrine Transporter Responses in Healthy Women
Authors: Moldovanova Iryna , Schroeder Christoph , Jacob Giris , Hiemke Christoph , Diedrich Andre , Luft Friedrich C. , Jordan Jens
Published: February 2008

Gender differences in human cardiovascular norepinephrine transporter function may be mediated through female sex hormones. We studied 16 healthy eumenorrheic women (25±1 years) during the early follicular phase (day 5±0) and midluteal phase (day 22±0) of the menstrual cycle. In a randomized, crossover, double-blind fashion, subjects ingested 8 mg of the selective norepinephrine transporter inhibitor reboxetine or placebo. We monitored heart rate, blood pressure, and thoracic bioimpedance at rest and during standard autonomic function tests, including head-up tilt. Venous estradiol and progesterone concentrations were higher in the luteal than in the follicular phase but did not differ between placebo and norepinephrine transporter inhibition testing days. On placebo, hemodynamics at rest and in response to different stressors were mostly identical between cycle phases. In the supine position, norepinephrine transporter inhibition increased blood pressure and stroke volume to a greater extent during the follicular than during the luteal phase. Conversely, the increase in heart rate and cardiac output with norepinephrine transporter inhibition was augmented in the luteal compared with the follicular phase. During head-up tilt with norepinephrine transporter inhibition, blood pressure and stroke volume decreased to a greater extent in the follicular than in the luteal phase. The tachycardic response to head-up tilt with norepinephrine transporter inhibition was augmented in the follicular phase. Our study suggests that sex hormones alter the hemodynamic response to norepinephrine transporter inhibition in women. The phenomenon may be explained by an effect of female sex hormones on norepinephrine transporter function, on compensatory cardiovascular responses, or both.
Gender Differences in Left Ventricular Structure and Function During Antihypertensive Treatment
Authors: Gerdts Eva , Okin Peter M. , de Simone Giovanni , Cramariuc Dana , Wachtell Kristian , Boman Kurt , Devereux Richard B.
Published: February 2008

In hypertensive patients with left ventricular hypertrophy, antihypertensive treatment induces changes in left ventricular structure and function. However, less is known about gender differences in this response. Baseline and annual echocardiograms until the end of study or a primary end point occurred were assessed in 863 hypertensive patients with electrocardiographic left ventricular hypertrophy aged 55 to 80 years (mean: 66 years) during 4.8 years of randomized losartan- or atenolol-based treatment in the Losartan Intervention for Endpoint Reduction in Hypertension Echocardiography substudy. Left ventricular hypertrophy was diagnosed as left ventricular mass divided by height
2.7
≥46.7 g/m
2.7
and 49.2 g/m
2.7
in women and men, respectively, and systolic function as ejection fraction and stress-corrected midwall fractional shortening. Women included more patients with obesity, isolated systolic hypertension, and mitral regurgitation (all
P
<0.01). Ejection fraction, stress-corrected midwall shortening, and prevalence of left ventricular hypertrophy were higher in women at baseline and at the end of study (all
P
<0.01). In particular, more women had residual eccentric hypertrophy (47% versus 32%;
P
<0.01) in spite of similar in-treatment reduction in mean blood pressure. In logistic regression, left ventricular hypertrophy at study end was more common in women (odds ratio: 1.61; 95% CI: 1.16 to 2.26;
P
<0.01) independent of other significant covariates. In linear regression analyses, female gender also predicted 2% higher mean in-treatment ejection fraction and 2% higher mean stress-corrected midwall shortening (both β=0.07;
P
<0.01). Hypertensive women in this study retained higher left ventricular ejection fraction and stress-corrected midwall shortening in spite of less hypertrophy regression during long-term antihypertensive treatment.
Wine Polyphenols Improve Endothelial Function in Large Vessels of Female Spontaneously Hypertensive Rats
Authors: López-Sepúlveda Rocío , Jiménez Rosario , Romero Miguel , Zarzuelo Maria José , Sánchez Manuel , Gómez-Guzmán Manuel , Vargas Félix , O’Valle Francisco , Zarzuelo Antonio , Pérez-Vizcaíno Francisco , Duarte Juan
Published: February 2008

Red wine polyphenols (RWPs) have been reported to prevent hypertension and endothelial dysfunction. Several individual RWPs exert estrogenic effects. We analyzed the possible in vivo protective effects on blood pressure and endothelial function of RWPs in female spontaneously hypertensive rats (SHR) and its relationship with ovarian function. RWPs (40 mg/kg by gavage) were orally administered for 5 weeks. Ovariectomized rats showed both increased isoprostaglandin F2αexcretion and aortic superoxide production and reduced relaxant response to acetylcholine and contraction to the endothelial nitric oxide synthase (eNOS) inhibitorl-NAME measured in the aorta but similar blood pressure, as compared with sham-operated rats. Moreover, in ovariectomized rats aortic eNOS expression was unchanged, whereas caveolin-1, angiotensin II receptor (AT)-1, and the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits p22phoxand p47phoxexpression was increased compared with sham-operated rats. In both ovariectomized and sham-operated SHR, RWPs reduced systolic blood pressure, urinary isoprostaglandin F2αexcretion, and aortic O2−production, improving the endothelium-dependent relaxant response to acetylcholine in SHR. These changes were associated with unchanged aortic eNOS expression, whereas caveolin-1 was increased and the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits p22phoxand p47phoxexpression was reduced. RWPs had no effect on the AT-1 overexpression found in ovariectomized animals. All these results suggest that a chronic treatment with RWPs reduces hypertension and vascular dysfunction through reduction in vascular oxidative stress in female SHR in a manner independent of the ovarian function.
Diagnostic Criteria of Vascular Dementia in CADASIL
Authors: Benisty Sarah , Hernandez Karen , Viswanathan Anand , Reyes Sonia , Kurtz Annie , O’Sullivan Michael , Bousser Marie-Germaine , Dichgans Martin , Chabriat Hugues
Published: February 2008

Background and Purpose—

Subcortical ischemic vascular dementia (SIVD) is a major subtype of vascular dementia (VaD). Recently, the diagnostic criteria of VaD have been modified to encompass this entity. Application of these criteria in CADASIL, a genetic model of SIVD, may help to better assess their significance. The aim of this study was to compare different sets of diagnostic criteria of VaD in a population of CADASIL patients.

Methods—

Different sets of diagnostic criteria of VaD (DSMIV, ICD10, standard NINDS-AIREN, modified NINDS-AIREN for SIVD) were applied to 115 CADASIL patients. Diagnosis of VaD was made through 2 steps: (1) diagnosis of dementia and (2) association of dementia to lesions of vascular origin. The percentage of patients satisfying the different sets and the concordance between these criteria was analyzed.

Results—

At least 1 set of criteria was satisfied for diagnosis in 29 subjects with dementia. In this group of patients, the sensitivity of the DSM IV, ICD 10, and standard NINDS-AIREN criteria for VaD was, respectively, 79%, 72%, and 45%. In contrast, the sensitivity of the NINDS-AIREN criteria for SIVD was 90%. The incomplete sensitivity of these last criteria was related to the absence of focal signs in some patients. The neuroimaging criteria were satisfied in all patients with dementia.

Conclusions—

The modified NINDS-AIREN criteria of SIVD are the most sensitive VaD criteria in CADASIL. Among these criteria, the neuroimaging criteria, although poorly specific to dementia, have a complete sensitivity. In contrast, focal signs were inconstant in CADASIL patients with dementia.
Independent Cognitive Effects of Atrophy and Diffuse Subcortical and Thalamico-Cortical Cerebrovascular Disease in Dementia
Authors: Swartz Richard H. , Stuss Donald T. , Gao Fuqiang , Black Sandra E.
Published: February 2008

Background and Purpose—

Brain atrophy, cortical infarction, and subcortical ischemic vasculopathy have all been associated with cognitive dysfunction. The interrelationships between these pathologies and their independent contributions to cognitive function remain unclear. Despite the high frequency of Alzheimer disease (AD) in those with clinically diagnosed vascular dementia, and the frequent findings of vascular disease in those with clinically diagnosed AD, many studies of brain-behavior relationships in dementia consider these populations separately. The present study sought to identify the correlates of independent domains of cognitive impairment in an unselected sample across a large range of severity and overlap of AD and VaD.

Methods—

Two hundred five individuals from the Sunnybrook Dementia Study recruited from a university Memory clinic had detailed neuropsychological testing and MRI quantification using a multi-step postprocessing algorithm. A factor analysis of the cognitive protocol yielded a 3-factor solution, provisionally labeled: (1) short-term memory and language, (2) attention and working memory, and (3) mental flexibility.

Results—

A factor analysis of brain measures identified 3 independent factors with measures of (1) brain atrophy, (2) subcortical vascular disease, and (3) strategic infarcts (anterior-medial thalamus and cortical infarcts). After accounting for the effects of age and education, measures of brain atrophy were the strongest correlates of all cognitive domains. Small vessel disease was independently associated with general severity, impaired short-term memory/language, and reduced mental flexibility, but not with poor working memory, presumably through disruption of frontal-subcortical connections. In contrast, strategic infarcts to anterior-medial thalamus and cortical gray matter were associated with poor short-term and working memory, but not with impairments in mental flexibility or global severity measures.

Conclusions—

These data support the hypothesis that the thalamico-cortical network subserves both short-term and working memory. The findings also suggest that each type of pathology (atrophy, small vessel disease, and strategic infarcts) contribute independently to the pattern of cognitive disabilities associated with dementia. Particular attention to cerebrovascular disease in deep white or gray matter structures of the thalamico-cortical system is certainly warranted.
Higher Stroke Incidence in the Spring Season Regardless of Conventional Risk Factors
Authors: Turin Tanvir Chowdhury , Kita Yoshikuni , Murakami Yoshitaka , Rumana Nahid , Sugihara Hideki , Morita Yutaka , Tomioka Nobuyoshi , Okayama Akira , Nakamura Yasuyuki , Abbott Robert D. , Ueshima Hirotsugu
Published: February 2008

Background and Purpose—

Seasonal variation in stroke incidence was examined using 14-year stroke registration data in a Japanese population. We also examined if this variation was modified by conventional stroke risk factors hypertension, diabetes mellitus, drinking, and smoking.

Methods—

Data were obtained from the Takashima Stroke Registry, which covers a stable population of ≈55 000 in Takashima County in central Japan. There were 1665 (men, 893; women, 772) registered first-ever stroke cases during 1988 to 2001. The average age of stroke onset for men and women patients was 69.4 and 74.2 years, respectively. Incidence rates (per 100 000 person-years) and 95% CI were calculated by gender, age, and stroke subtype for winter, spring, summer, and autumn. After stratifying patients by their risk factor history, the OR (with 95% CI) of having a stroke in autumn, winter, and spring were calculated, with summer serving as a reference.

Results—

Among the seasons, stroke incidence per 100 000 person-years was highest in the spring (231.3; 95% CI, 211.1 to 251.5). Spring incidence was highest in both men (240.8; 95% CI, 211.5 to 270.2) and women (222.1; 95% CI, 194.4 to 249.9), and in subjects younger than 65 years (72.6; 95% CI, 60.0 to 85.3) and 65 years or older (875.9; 95% CI, 787.5 to 964.3). Among stroke subtypes, spring incidence was highest for cerebral infarction (154.7; 95% CI, 138.2 to 171.2) and cerebral hemorrhage (53.7; 95% CI, 44.0 to 63.4). The spring excess in stroke incidence was observed regardless of the presence or absence of the risk factor histories.

Conclusions—

Stroke incidence appears to be highest in the spring among a Japanese population regardless of conventional risk factor history. Factors that explain this excess need further investigation.
Histological Characterization of Restenotic Carotid Plaques in Relation to Recurrence Interval and Clinical Presentation
Authors: Hellings Willem E. , Moll Frans L. , de Vries Jean-Paul P.M. , de Bruin Peter , de Kleijn Dominique P.V. , Pasterkamp Gerard
Published: February 2008

Backgrounds and Purpose—

Restenosis is an important complication after carotid endarterectomy, but little is known about plaque composition in early versus late restenosis and which plaque characteristics are associated with symptomatic clinical presentation of restenotic lesions.

Methods—

Endarterectomy specimens of 822 consecutive patients undergoing carotid endarterectomy (33 restenotic; 789 primary) were subjected to histological examination for the presence of macrophages, smooth muscle cells, collagen, calcifications, luminal thrombus, intraplaque bleeding and lipid core size.

Results—

Early restenotic plaques showed marked accumulation of smooth muscle cells and fibrous tissue, whereas late restenotic plaques demonstrated increased macrophage infiltration, calcification and lipid core (
P
trend <0.05), resembling primary plaques. Patients with symptomatic restenosis had plaques with higher macrophage infiltration (
P
=0.01) and a larger lipid core (
P
=0.02) than asymptomatic patients, independent of recurrence interval.

Conclusions—

Restenosis occurring >5 years after primary carotid endarterectomy resembles primary plaques. Symptomatic presentation of restenotic lesions is independently associated with an unstable plaque phenotype.
Genetics of Intracranial Aneurysms
Authors: Ruigrok Ynte M. , Rinkel Gabriel J.E.
Published: February 2008

Background and Purpose—

Genetic determinants probably play a role in the development of intracranial aneurysms. We review the present knowledge on this issue.

Methods—

This work entailed a comprehensive search of the literature, a critical appraisal of the identified papers, and a personal view of limitations and future directions.

Results—

We identified 10 genome-wide linkage studies in families and sib pairs with intracranial aneurysms. These studies have identified several loci, but only 4 (1p34.3–p36.13, 7q11, 19q13.3, and Xp22) have been replicated in different populations. For the loci on 1p34.3–p36.13 and 7q11 association with positional candidate genes has also been demonstrated: for locus on 1p34.3–p36.13 association with the perlecan gene and for 7q11 association with the elastin and collagen type 1 A2 genes.

Conclusions—

The progress in identifying genetic determinants for intracranial aneurysms is modest. Reasons for this modest progress include limitations of the present studies, limitations because of the nature of the disease, and limitations in our concept of aneurysms and aneurysm development. Future studies may benefit from strict definitions of familial aneurysms, reduced phenotypic heterogeneity (separating ruptured from unruptured aneurysms, and within these subsets probably also reduce morphological heterogeneity, eg, by grouping similar sites of aneurysms), taking into account age and other risk factors of the patients with aneurysms, and sufficiently large numbers of patients. In future studies we should not only look for genetic determinants of aneurysms, but also for genetic determinants of rupture of aneurysms. This would help in selecting patients for preventive treatment of aneurysms.
MRI Detection of Early Blood-Brain Barrier Disruption
Authors: Hjort Niels , Wu Ona , Ashkanian Mahmoud , Sølling Christine , Mouridsen Kim , Christensen Søren , Gyldensted Carsten , Andersen Grethe , Østergaard Leif
Published: February 2008

Background and Purpose—

Blood-brain barrier disruption may be a predictor of hemorrhagic transformation (HT) in ischemic stroke. We hypothesize that parenchymal enhancement (PE) on postcontrast T1-weighted MRI predicts and localizes subsequent HT.

Methods—

In a prospective study, 33 tPA-treated stroke patients were imaged by perfusion-weighted imaging, T1 and FLAIR before thrombolytic therapy and after 2 and 24 hours.

Results—

Postcontrast T1 PE was found in 5 of 32 patients (16%) 2 hours post-thrombolysis. All 5 patients subsequently showed HT compared to 11 of 26 patients without PE (
P
=0.043, specificity 100%, sensitivity 31%), with exact anatomic colocation of PE and HT. Enhancement of cerebrospinal fluid on FLAIR was found in 4 other patients, 1 of which developed HT. Local reperfusion was found in 4 of 5 patients with PE, whereas reperfusion was found in all cases of cerebrospinal fluid hyperintensity.

Conclusions—

PE detected 2 hours after thrombolytic therapy predicts HT with high specificity. Contrast-enhanced MRI may provide a tool for studying HT and targeting future therapies to reduce risk of hemorrhagic complications.
Statin Therapy for Stroke Prevention
Authors: Nassief Abdullah , Marsh James D.
Published: February 2008

Background and Purpose—

Statins are widely used to reduce the risk of stroke in patients with coronary artery disease (CAD), but less so in patients without CAD. We reviewed recent trials for new evidence for the reduction in risk of stroke.

Summary of Review—

In patients with CAD, moderate-intensity statin treatment has been associated with reductions in risk of stroke, with no increase in hemorrhagic stroke. Additionally, in the TNT trial, intensive lipid lowering provided further stroke risk reduction compared with moderate lipid lowering in patients with stable CAD. Evidence is now available that statin therapy also reduces stroke risk in patients without CAD but at high cardiovascular risk, or with diabetes mellitus. The SPARCL trial showed that intensive statin therapy started within 6 months after a cerebrovascular event significantly reduced stroke risk and stroke severity. Low cholesterol levels have been associated with increased risk of hemorrhagic stroke, but although an increased risk of hemorrhagic stroke was observed in patients with prior hemorrhagic stroke in SPARCL, this was not related to low-density lipoprotein cholesterol levels. Clinical trials have recruited few patients with both coronary and cerebrovascular disease, but these patients are also expected to experience significant cardiovascular benefit with statin therapy.

Conclusions—

Trial data show that statins reduce the risk of stroke, in addition to providing cardiovascular benefits. Consequently, physicians should consider statin therapy in all patients at high risk of stroke.
Regional White Matter Pathology in Mild Cognitive Impairment
Authors: Delano-Wood Lisa , Abeles Norm , Sacco Joshua M. , Wierenga Christina E. , Horne Nikki R. , Bozoki Andrea
Published: February 2008

Background and Purpose—

Associations between regional white matter lesion pathology and neuropsychological performance across the aging spectrum are not well understood and, to date, research has been largely contradictory and inconclusive. The current study set out to clarify some of the inconsistencies in the literature by relating volumetric analyses of white matter lesions (deep white matter lesions and periventricular lesions) to neuropsychological performance in a large clinical sample of older adults diagnosed with mild cognitive impairment.

Methods—

Seventy older adults with mild cognitive impairment were administered a comprehensive neuropsychological battery. White matter lesions identified on T2-weighted FLAIR images were quantified using a semi-automated volumetric approach (pixel thresholding).

Results—

Results showed that, in contrast to performance on memory and naming tasks, total white matter lesions strongly predicted executive impairments, slowed processing speed, and visuospatial/construction difficulties. In addition, separate regression analyses demonstrated that results were primarily accounted for by deep white matter lesions (but not periventricular lesions), most likely due to frontal-subcortical circuitry disruption. Moreover, deep white matter lesions, but not periventricular lesions, significantly predicted overall poorer neuropsychological functioning after controlling for age, education, and level of depression.

Conclusions—

Taken together, findings demonstrate a differential influence of lesion type on cognitive impairment in mild cognitive impairment and implicate deep white matter lesions as being most detrimental in terms of neuropsychological functioning. Clinical, theoretical, and methodological implications of these results are discussed.
Pharmacokinetics of Licarbazepine in Healthy Volunteers: Single and Multiple Oral Doses and Effect of Food
Authors: Souppart Claire , Gardin Anne , Greig Gerard , Balez Sebastien , Batard Yannick , Krebs‐Brown Axel , Appel‐Dingemanse Silke
Published: February 2008

Two studies characterized single‐ and multiple‐dose pharmacokinetics of licarbazepine immediate‐release tablets and food effects on single‐dose pharmacokinetics. In 1 study, 12 volunteers received 500 mg licarbazepine on day 1, 500 mg bid on days 3 to 6, and 500 mg on day 7. In the second study, 12 subjects received one 500‐mg licarbazepine dose under fasted and fed conditions. After multiple dosing, geometric mean (%CV) Cmaxss, Cminss, and AUCτ were 77.6 μmol/L (18), 45.3 μmol/L (25), and 747 hṁμmol/L (19), respectively, with a tmax of 2 hours. Mean half‐lives were 9.3 and 11.3 hours for single and multiple dosing, respectively. Food had no clinically significant effect on single‐dose pharmacokinetics. Half‐life (∼10 hours) and low intersubject variability in main pharmacokinetic parameters were similar under fasted and fed conditions. Median tmax increased from 1.5 to 2.5 hours with food. Licarbazepine is well tolerated and has predictable pharmacokinetics.
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic Properties of Taranabant, a Novel Selective Cannabinoid‐1 Receptor Inverse Agonist, for the Treatment of Obesity: Results From a Double‐Blind, Placebo‐Controlled, Single Oral Dose Study in Healthy Volunteers
Authors: Addy Carol , Li Susie , Agrawal Nancy , Stone Julie , Majumdar Anup , Zhong Ling , Li Hankun , Yuan Jinyu , Maes Andrea , Rothenberg Paul , Cote Josee , Rosko Kim , Cummings Corinne , Warrington Steven , Boyce Malcolm , Gottesdiener Keith , Stoch Aubrey , Wagner John
Published: February 2008

Taranabant is a novel cannabinoid CB‐1 receptor (CB1R) inverse agonist in clinical development for the treatment of obesity. This double‐blind, randomized, placebo‐controlled, single oral dose study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of taranabant (0.5–600 mg) in 24 healthy male volunteers. Single‐dose AUC0‐∞ and Cmax values for taranabant increased approximately linearly ith dose up to 200 mg, with slightly less than dose‐proportional increases in AUC0‐∞ and Cmax values for doses >200 mg. Plasma taranabant had a biphasic disposition, with a median tmax of 1 to 2.5 hours and a terminal elimination tl/2 of 38 to 69 hours. Coadministration of taranabant with a high‐fat meal led to a 14% increase in Cmax and a 74% increase in AUC0‐∞, Clinical adverse experiences ssociated with single doses of taranabant were generally mild and transient. Of the 198 clinical adverse experiences reported, the most common drug‐related ones were nausea (36), headache (22), drowsiness (14), abdominal discomfort/abdominal pain/stomachache (14), hiccups (9), dizziness (8), decreased appetite (7), increased bowel movement (7), mood change (6), tiredness (4), vomiting (4), and sweating increased (4). Taranabant has pharmacokinetic characteristics suitable for a once‐daily dosing regimen.
Disentrenching Experiment
Authors: Bonneuil Christophe , Joly Pierre-Benoit , Marris Claire
Published: February 2008

The paper investigates how field experimentation of genetically modified crops became central to the French controversy on genetically modified organisms (GMOs) in recent years. Initially constructed in the 1980s as a cognitive endeavor to be preserved from lay interference, field trials of genetically modified crops were reconceived as “an intrusion in the social space,” which had to be negotiated with actors from that space. In order to analyze this transformation, the authors suggest that it is necessary to develop an interpretive framework that combines theoretical perspectives from science and technology studies and the sociology of social problems, and emphasizes the importance of the way in which actors compete in a heterogeneous public space, to put forward alternative framings of problems. The authors present a detailed analysis of the interactions and conflicts between actors in diverse social arenas in order to better understand the dynamics of this sociotechnical controversy.
Gender and National ICT Policy in Africa: issues, strategies, and policy options
Authors: Olatokun Wole Michael
Published: February 2008

The paper commences with a review of the concept of Information Communication technology (ICT) and points out how it has become a potent force in transforming social, economic and political life globally. It then discusses the linkage between gender and ICT especially how ICT has widened the digital divide gap between Africa and the rest of the world on one hand, and between males and females on the other. It later gives an overview of the ICT policy formulation situation in Africa pointing out the gender provisions in the national ICT policy documents of some African countries. It then reviews illiteracy rates and access to telephone facilities, computers, and Internet facilities in Africa and indicates that there is a digital divide on the continent between those who have access to the Internet and related technologies and those who do not. It finally presents the policy options and strategies to be adopted by African governments to enable women to benefit from opportunities offered by ICT. The paper concludes by submitting that unless gender issues are incorporated in national ICT policies in Africa, the digital divide will continue to widen and most women that live in African rural populations would continue to be excluded from the benefits of ICT.
Toward a Transactional Model of Parent-Adolescent Relationship Quality and Adolescent Psychological Adjustment
Authors: Fanti Kostas A. , Henrich Christopher C. , Brookmeyer Kathryn A. , Kuperminc Gabriel P.
Published: February 2008

The present study includes externalizing problems, internalizing problems, mother-adolescent relationship quality, and father-adolescent relationship quality in the same structural equation model and tests the longitudinal reciprocal association among all four variables over a 1-year period. A transactional model in which adolescents' internalizing and externalizing problems are negatively related to the quality of adolescents' relationships with their parents and relationship quality is related to internalizing and externalizing problems is hypothesized. Moderation by gender, ethnicity, and parental marital status is also investigated. The sample consists of 246 boys and 253 girls from the sixth and seventh grades of a large public middle school. The study's final model suggests a longitudinal, reciprocal association between the quality of adolescents' relationships with their mothers and internalizing problems. Results suggest longitudinal unidirectional effects from externalizing problems to the quality of adolescents' relationships with their fathers and from the quality of adolescents' relationships with their mothers to externalizing problems.
Apples and Oranges
Authors: McElhaney Kathleen Boykin , Porter Maryfrances R. , Thompson L. Wrenn , Allen Joseph P.
Published: February 2008

This study examines the hypothesis that effective parental influence stems from the qualities of the parent-adolescent relationship rather than from explicit efforts to alter adolescents' behaviors. Adolescents' versus parents' perceptions of parental influence as predictors of parent-adolescent relationship quality and of adolescents' social functioning are examined using observational and multireporter data obtained from a sample of 167 adolescents (90 female, 77 male; age M = 13.34 years, SD = 0.65), their parents, and their same-sex peers. Analyses revealed that adolescents' and parents' perceptions of parental influence were uncorrelated with one another and were differentially related to qualities of adolescents' relationships with parents and friends. Adolescents' perceptions of high parental influence were linked to observations and self-reports of warm, supportive relationships with parents (particularly mothers). In contrast, parents' reports of high influence were linked to lower levels of adolescent autonomy with parents and friends and less relatedness with mothers and friends.
Sociological, Social Psychological, and Psychopathological Correlates of Substance Use Disorders in the U.S. Jail Population
Authors: Kerridge Bradley T.
Published: February 2008

The objective of this study was to examine sociological, social psychological, and psychopathological correlates of substance abuse disorders in a nationally representative sample of jail inmates. Criminal history and clinical factors most strongly differentiated convicted inmates with and without substance use disorders regardless of current index offense. Policy implications are discussed in terms of targeting antisocial attitudes and peer associations and more effective clinical treatments for substance use disorders among the inmate population. High rates of co-occurring depression symptoms and anger dyscontrol found among inmates with substance use disorders in this study underscore the need for assessment and evaluation of specialized programs for co-occurring disorders and anger management programs among U.S. inmates.
Headache in Children's Drawings
Authors: Wojaczyńska-Stanek Katarzyna , Koprowski Robert , Wróbel Zygmunt , Gola Małgorzata
Published: February 2008

Headache is a common health problem in childhood. Children's drawings are helpful in the diagnosis of headache type. Children, especially younger ones, communicate better through pictures than verbally. The aim of the present study is to evaluate the usefulness of drawings of the child's headache in the diagnostic process carried out by a pediatrician and a pediatric neurologist. At the beginning of a visit in a neurological clinic, or on the first day of hospitalization, the child was asked, “Please draw your headache,” or “How do you feel your headache?” without any additional explanations or suggestions. Clinical diagnosis of headache type was made on the basis of the standard diagnostic evaluation. For the purpose of this study, children's headaches were categorized as migraine, tension-type headache, or “the others.” One hundred twenty-four drawings of children with headaches were analyzed by 8 pediatricians and 8 pediatric neurologists. The analysts were unaware of the clinical history, age, sex, and diagnosis of the patients. The clinical diagnosis was considered the “gold standard” to which the headache drawing diagnosis was compared. There were 68 girls 5—18 years of age and 56 boys 7—18 years of age. Of the 124 children, 40 were clinically diagnosed with migraine (32.2%), 47 with tension-type headache (37.9%), and 37 (29.8%) as the others. Children with migraine most frequently draw sharp elements. Children with tension-type headache mainly drew compression elements and pressing elements. In the group of “the other” headaches, 21 children were diagnosed with somatoform disorders. The most frequent element in this group's drawings was a whirl in the head. Colors used most frequently were black and red, which signify severe pain. There was no difference in sensitivity of diagnoses between neurologists and pediatricians. Because the evaluation of drawings by children with headaches done both by pediatricians and pediatric neurologists was correct for approximately half of the children, the authors decided to prepare a set of test pictures, including characteristic presentations of pain. Preparing a ready set of test drawings may facilitate differentiation for the inexperienced doctors and encourage those children who refuse to draw.
Cerebral Perfusion Pressure—Targeted Approach in Children With Central Nervous System Infections and Raised Intracranial Pressure: Is It Feasible?
Authors: Shetty Rakshay , Singhi Sunit , Singhi Pratibha , Jayashree M.
Published: February 2008

This study was conducted to evaluate the feasibility of cerebral perfusion pressure—targeted therapy in children with raised intracranial pressure caused by central nervous system infection. A prospective observational pilot study was conducted in the pediatric intensive care unit of a tertiary care teaching hospital. Twenty children (ages 6 months to 12 years) with a clinical diagnosis of meningitis or meningoencephalitis were included. Intracranial pressure and blood pressure monitoring were initiated soon after enrollment. Interventions to reduce intracranial pressure and elevate blood pressure were used to achieve a target cerebral perfusion pressure of greater than 70 mm Hg in children 2 years of age or older and greater than 60 mm Hg in children less than 2 years. Therapies used to achieve target cerebral perfusion pressure were initial fluid boluses (in 14 patients), vasopressors (in 8), and mannitol (in 10). The target cerebral perfusion pressure was achieved in 6 patients, whereas a cerebral perfusion pressure greater than 50 mm Hg was achieved in 16 patients. All 4 patients with mean cerebral perfusion pressure less than 50 mm Hg died of intractable, raised intracranial pressure. In contrast, only 3 of 16 patients with mean cerebral perfusion pressure more than 50 mm Hg died. In children with raised intracranial pressure caused by central nervous system infection, it was feasible to achieve a cerebral perfusion pressure greater than 50 mm Hg, mainly by increasing the blood pressure within the first 24 hours and by reducing intracranial pressure after the first 24 hours.
Lafora Progressive Myoclonus Epilepsy: Disease Course Homogeneity in a Genetic Isolate
Authors: Turnbull Julie , Kumar Santosh , Ren Zhi-Ping , Muralitharan Shanmugakonar , Naranian Taline , Ackerley Cameron A. , Minassian Berge A.
Published: February 2008

Lafora epilepsy is characterized by starch formation in brain and skin and is diagnosed by skin biopsy or mutation detection. It has variable ages of onset (6-19 years) and death (18-32 years) even with the same mutation, likely due to extramutational factors. The authors identified 14 Lafora epilepsy patients in the genetic isolate of tribal Oman. The authors show that in this homogeneous environment and gene pool, the same mutation, EPM2B-c.468-469delAG, results in highly uniform ages of onset (14 years) and death (21 years). Biopsy, on the other hand, was not homogeneous (positive in 4/5 patients) and is, therefore, less sensitive than mutation testing.
Spinal Muscular Atrophy With Respiratory Distress Type 1 (SMARD1)
Authors: Kaindl Angela M. , Guenther Ulf-Peter , Rudnik-Schöneborn Sabine , Varon Raymonda , Zerres Klaus , Schuelke Markus , Hübner Christoph , von Au Katja
Published: February 2008

Autosomal recessive spinal muscular atrophy with respiratory distress type 1 (SMARD1), recently referred to as distal spinal muscular atrophy 1 (DSMA1; MIM#604320) and also known as distal hereditary motor neuropathy type 6 (dHMN6 or HMN6), results from mutations in the IGHMBP2 gene on chromosome 11q13.3 encoding the immunoglobulin µ-binding protein 2. In contrast to the infantile spinal muscular atrophy type 1 (SMA1; Werdnig-Hoffmann disease) with weakness predominantly of proximal muscles and bell-shaped thorax deformities due to intercostal muscle atrophy, infants with distal spinal muscular atrophy 1 usually present with distal muscle weakness, foot deformities, and sudden respiratory failure due to diaphragmatic paralysis that often requires urgent intubation. In this article, the authors review the clinical, neuropathological, and genetic aspects of distal spinal muscular atrophy 1 and discuss differential diagnoses.
Blinded by Science
Authors: Robbers Monica L. P.
Published: February 2008

Using a social construction of reality perspective, this article examines the social distance between popular media depictions of criminal investigations and reality, and the extent to which these depictions influence criminal jury trials. Data were collected from a nationally representative, random sample of trial counsel and judges and was analyzed using qualitative methods. Results indicate there is a great deal of social distance between popular media depictions of criminal investigation and reality. Moreover, jurors appear to have no tools to assess the credibility of forensic testing on television shows or in trials. Furthermore, the social construction of reality on forensic television shows has not only influenced jury decisions but has also affected the ways in which trial counsel and judges do their jobs. Suggestions for further research and discussion of public policy implications are included in the study.