bluuebunny/crossref_metadata_2025 huggingface dataset:
Dipyridamole-Associated Headache in Stroke Patients – Interindividual Differences?
Authors: Lökk J.
Published: June 2009

Background: Secondary pharmacological prevention of ischemic stroke or transient ischemic attack (TIA) is often provided with acetylsalicylic acid (ASA), dipyridamole (DP) or a combination of the two. A problem with DP is the occurrence of headache, sometimes leading to medication cessation. By using a titration regime of DP the incidence of headache gets lower. However, there are no studies on interindividual differences in the incidence of headache with regard to age, gender, localization of stroke and the number of days since stroke onset. Method: 20 stroke units in Sweden recruited newly diagnosed stroke and TIA patients in need for thrombocyte antiaggregating therapy. They were offered a titration regime of the combination ASA 25 mg + DP 200 mg once daily for 5 days followed by twice daily. Baseline characteristics of the patients were recorded and headache symptoms were filled in by each patient in a diary for 10 consecutive days. Rescue medication with paracetamol was optional. Results: 174 ischemic stroke patients with a mean age of 70.3 years, 63% men and 37% women, were recruited. Headache of any kind was reported in 70 patients (40.2%) and 37 (21.3%) assessed the headache as moderate/severe. Six patients stopped medication due to headache. A subsiding character of the headache was found with a mean of 3.1 days. Patients with TIA had a significantly higher risk of getting headache compared to manifest stroke, regardless of localization. There was a trend towards higher risk in younger age groups and females. No effect was seen on the number of days since stroke onset. Conclusion: DP is often associated with subsiding headache, however, with only few patients stopping medication due to headache. Being a younger female with a TIA seems to increase the risk of getting headache when having DP medication. Careful and adequate information about the possibly occurring headache should be given to patients prescribed a DP medication in order to increase compliance and optimize the pharmacological secondary stroke prevention.
Serotonin Transporter Gene Polymorphic Element 5-HTTLPR Increases the Risk of Sporadic Parkinson’s Disease in Italy
Authors: Albani Diego , Vittori Angelica , Batelli Sara , Polito Letizia , De Mauro Stefania , Galimberti Daniela , Scarpini Elio , Lovati Carlo , Mariani Claudio , Forloni Gianluigi
Published: June 2009

Parkinson’s disease (PD) is a neurodegenerative disorder causing muscular rigidity, resting tremor and bradykinesia. We conducted an association study assessing how PD risk in Italy was influenced by the serotonin transporter gene (SLC6A4) polymorphic region 5-HTTLPR, consisting of an insertion/deletion (long allele-L/short allele-S) of 43 bp in the SLC6A4 promoter region. The SLC6A4 promoter single nucleotide polymorphism rs25531(A→G) was evaluated too. We collected 837 independent subjects (393 PD, 444 controls). An association between the 5-HTTLPR polymorphism and risk of PD (S/S genotype OR [95% CI]: 1.7[1.2–2.5], p = 0.002) was found. The rs25531 and the haplotype 5-HTTLPR/rs25531 did not associate with risk of PD. Our data indicate that the 5-HTTLPR polymorphic element within the SLC6A4 promoter may govern the genetic risk of PD in Italians.
Tuberculous Temporal Brain Abscess Mimicking Otogenic Pyogenic Abscess
Authors: Muzumdar D. , Balasubramaniam S. , Melkundi S.
Published: June 2009

Tuberculous brain abscess is a rare manifestation of central nervous system tuberculosis. We report the case of a tuberculous temporal lobe abscess in a 14-year-old female child that mimicked an otogenic pyogenic brain abscess. The patient had no prior history of tuberculosis. She had chronic otitis media and presented with signs of raised intracranial tension. Radiological imaging was suggestive of an acute pyogenic left temporal lobe abscess. A left temporal craniotomy was performed and the abscess was completely excised. Histological examination was consistent with a chronic abscess, and bacterial cultures were negative. A left radical mastoidectomy was also carried out. However, she presented with repeated abscess formation at the same site over the next 8 weeks, which was refractory to surgical therapy and broad-spectrum antibiotic administration. Furthermore, the purulent exudate showed strong positivity in the PCR test for tubercular bacilli. After administration of antituberculous treatment, she showed gradual clinical and radiological improvement. At follow-up after 2 years, she is asymptomatic. CT imaging at 2 years showed total resolution of abscess. Tuberculous abscess in the temporal lobe following otogenic infection has not been reported in the pediatric population. Although rare, the possibility of tuberculous etiology should be borne in mind as a differential diagnosis of acute abscess of otogenic origin, especially in endemic areas where the incidence of chronic otitis media as well as tuberculosis is high. The pathogenesis and treatment of tuberculous brain abscess in children is reviewed in light of the current literature on the subject.
Ventricular Reverse Remodeling Early after Mitral Valve Repair for Severe Chronic Mitral Regurgitation with Atrial Fibrillation
Authors: Song Bong Gun , On Young Keun , Jeon Eun-Seok , Park Ji Han , Choi Jin-Oh , Lee Sang-Chol , Park Seung Woo , Kim June Soo , Park Pyo Won
Published: June 2009

Objective: Chronic mitral regurgitation (MR) results in volume overload followed by left ventricular (LV) and left atrial remodeling. The aim of this study was to investigate the relation of clinical, echocardiographic findings and N-terminal B-type natriuretic peptide (NT-proBNP) to LV reverse remodeling (LVRR) early after valve repair for severe chronic MR concomitant with modified maze procedure for atrial fibrillation (AF). Methods: We retrospectively evaluated 60 patients who were surgically treated for severe chronic MR and AF. Plasma NT-proBNP and echocardiographic measurements were performed before surgery, before discharge and 12 months after surgery. Echocardiogram was additionally performed at 6 months. LVRR was assessed by looking at regression of LV mass index (LVMI) using echocardiography. Results: Fifty-two patients (87%) were classified in the LVRR group, defined as having a postoperative reduction in LVMI. The remaining patients were classified in the non-LVRR group. The non-LVRR group was older (p = 0.004), had a significantly higher ratio of patients with hypertension (p = 0.022), higher NT-proBNP levels (p = 0.007) and lower ejection fraction (p = 0.034) compared to the LVRR group. In multivariate analysis, age (odds ratio 0.874, p = 0.013) and NT-proBNP levels (odds ratio 0.185, p = 0.040) were independent predictors of LVRR. Conclusions: Preoperative lower NT-proBNP levels and younger age may predict LVRR early after surgical correction of chronic MR with AF.
Huntington’s Disease – New Perspectives Based on Neuroendocrine Changes in Rodent Models
Authors: Petersén Åsa , Hult Sofia , Kirik Deniz
Published: June 2009

Huntington’s disease (HD) is a neurodegenerative disorder caused by an expanded CAG repeat in the huntingtin gene. Although it is characterized by progressive motor impairments, cognitive changes and psychiatric disturbances are major components of the disease. In addition, recent studies have shown that other non-motor symptoms such as alterations in sleep pattern, disruption of the circadian rhythm and increased energy metabolism are common and occur early. Emerging evidence suggests that the latter symptoms are likely results of disturbed functions of the hypothalamus and neuroendocrine circuits, which are known to be central in the regulation of emotion, sleep and metabolism. Whereas clinical data are essential to define key pathological features of HD, animal models that can recapitulate the neurobiological and behavioral features of the disorder are critical tools to elucidate the underlying pathogenic mechanisms. Recent studies employing different HD rodent models have been instrumental in identifying a number of neuroendocrine alterations as well as in highlighting novel potential disease pathways. This review summarizes the current state of knowledge derived from neuroendocrine studies in rodent models of HD in light of clinical relevance and points to future implications for this emerging field.
Global Gene Analysis of Erigeron canadensis-Treated TNF-α-, IL-4- and IL-1β-Stimulated A549 Human Epithelial Cells
Authors: Sohn Sung-Hwa , Ko Eunjung , Oh Bang-Gul , Kim Jinju , Choi Eunsung , Kim Sung-Hoon , Kim Yangseok , Shin Minkyu , Hong Moochang , Bae Hyunsu
Published: June 2009

Background/Aims: This study was conducted to evaluate the anti-inflammatory mechanisms of Erigeron canadensis (EC) on the tumor necrosis factor-α (TNF-α)-, interleukin (IL)-4- and IL-1β-induced stimulation of A549 cells. Methods: In the present study, the anti-inflammatory effects of EC on TNF-α-, IL-4- and IL-1β-induced A549 cells were determined by analyzing eotaxin secretion using ELISA. In addition, the effects of ECon gene expression profiles in stimulated A549 cells were evaluated by microarray analysis. Results: Oligonucleotide microarray analysis revealed that inflammatory-related genes such as NOS1, NOS2A, IL-1β, IL-8 and CSF2 and cell adhesion-related genes such as SELE, MMP3, VCAM1, ICAM1, ITGA7 and ITGB2 were downregulated in EC-treated A549 cells that had been pretreated with TNF-α, IL-4 and IL-1β. In addition, significant decreases in Eotaxin, ICAM, VCAM and IL-8 gene expression were observed in EC-treated A549 cells. Conclusions: EC has an anti-inflammatory effect in stimulated A549 cells. Microarray-based genomic survey is a high-throughput approach that is suitable for the evaluation of gene expression in cell lines that have been treated with EC.
Luteinizing Hormone-Releasing Hormone Receptor-Targeted Chemotherapy Using AN-152
Authors: Emons Günter , Sindermann Herbert , Engel Jürgen , Schally Andrew V. , Gründker Carsten
Published: June 2009

The luteinizing hormone-releasing hormone (LHRH; also known as gonadotropin-releasing hormone) receptor can be utilized for targeted chemotherapy with cytotoxic LHRH analogues such as AN-152, in which doxorubicin is linked to [D-Lys6]LHRH. Our studies demonstrate receptor-mediated actions of the cytotoxic LHRH analogue AN-152 in LHRH receptor-positive endometrial and ovarian tumors in vivo. Intravenous administration of AN-152 is far less toxic and inhibits the growth of LHRH receptor-positive tumors better than equimolar doses of the cytotoxic agent doxorubicin. AN-152 has no antitumor activity in LHRH receptor-negative cancers. This provides evidence for the principle of targeted cytotoxic chemotherapy to tumor cells expressing LHRH receptors. In addition, we were able to show that LHRH binding sites were only slightly reduced after AN-152 treatment. Therefore, repeated therapy is considered to be possible. The majority (80%) of human endometrial and ovarian cancers and about 50% of breast cancers express LHRH receptors. In addition, apart from reproductive organs, which are normally removed during surgical therapy, other organs and hematopoietic stem cells do not express LHRH receptors. Thus, cytotoxic LHRH analogues such as AN-152 appear to be suitable drugs for a more efficacious and less toxic targeted chemotherapy for endometrial and ovarian cancers. A recently finished phase I study assessed the dose limitations, maximum tolerated dose and pharmacokinetics of AN-152 given once every 3 weeks in patients with gynecological and breast cancers. A phase II study was started in January 2008.
Immunoglobulin A Nephropathy in China: Progress and Challenges
Authors: Cai Guang-Yan , Chen Xiang-Mei
Published: June 2009

Background: IgA nephropathy (IgAN) is the most common primary glomerulonephritis in China. In about 20% of patients it will lead to renal insufficiency within 10 years, even in those with clinically early IgAN, which causes a great burden for patients and society. Methods: We reviewed basic and clinical research work in China. Comparisons between data from China and those from other countries were made. Results: The genetic variations conferring susceptibility to IgAN and disease progression as well as the pathogenic role of polymeric IgA1 were investigated in Chinese patients. Clinical features of Chinese IgAN with isolated microscopic hematuria, malignant hypertension, crescentic glomerulonephritis, intrarenal arterial and tubulointerstitial lesions have been characterized. Clinical trials showed that the combined therapy with urokinase + ACEI, or steroid + ACEI was more effective than with ACEI alone in reducing proteinuria and protecting renal function. The therapeutic role of MMF in IgAN remains debated, although two Chinese studies demonstrated its efficacy. Severe pneumonia can possibly occur in some cases after MMF administration for 3 months. Conclusion: IgAN remains a great challenge to Chinese nephrologists. In-depth basic studies and multicenter clinical trials are needed in the future.
The Selective Vitamin D Receptor Activator for Albuminuria Lowering (VITAL) Study: Study Design and Baseline Characteristics
Authors: Lambers Heerspink H.J. , Agarwal R. , Coyne D.W. , Parving H.-H. , Ritz E. , Remuzzi G. , Audhya P. , Amdahl M.J. , Andress D.L. , de Zeeuw D.
Published: June 2009

Background: Patients with diabetic nephropathy are at high risk for further progressive renal function loss. Treatments that decrease albuminuria have been linked with renal and cardiovascular protection. However, even when taking optimal treatment, residual renal and cardiovascular risk remains high which correlates with the magnitude of residual albuminuria. Use of vitamin D receptor activators, such as calcitriol and paricalcitol, is associated with improved sur- vival. A small study with paricalcitol showed reductions in albuminuria. The VITAL study tests the hypothesis whether paricalcitol persistently reduces albuminuria in diabetic subjects already receiving angiotensin-converting enzyme inhibitor (ACEI) and/or angiotensin receptor blocker (ARB) therapy. Methods: Randomization in this double-blind trial is equal allocation to paricalcitol 1 μ/day, 2 μg/day, or placebo. Inclusion criteria include: a diagnosis of type 2 diabetes, urinary albumin/creatinine ratio (UACR) between 100–3,000 mg/g, estimated glomerular filtration rate (eGFR) between 15–90 ml/min/1.73 m2, serum calcium <9.8 mg/dl, and parathyroid hormone (PTH) between 35–500 pg/ml. Results: Baseline characteristics of the 281 subjects are: 69% men, mean age 64.9 ± 10.4 years, eGFR 40.7 ± 16.7 ml/min, median UACR (interquartile range) 612.3 mg/g (281–1,181 mg/g) and PTH 98.4 ± 63.8 pg/ml. Conclusion: This trial will be the first clinical test of the hypothesis that paricalcitol possesses pleiotropic effects and can modulate albuminuria in the setting of ACEI and/or ARB therapy. Results will have important clinical implications and are expected in November 2009.
Importance of Junctional Adhesion Molecule-C for Neointimal Hyperplasia and Monocyte Recruitment in Atherosclerosis-Prone Mice–Brief Report
Authors: Shagdarsuren Erdenechimeg , Djalali-Talab Yassin , Aurrand-Lions Michel , Bidzhekov Kiril , Liehn Elisa A. , Imhof Beat A. , Weber Christian , Zernecke Alma
Published: June 2009

Objective—

Although junctional adhesion molecule (JAM)-C has been implicated in the control of inflammatory leukocyte recruitment, its role in neointima formation after arterial injury has not been elucidated.

Methods and Results—

In apolipoprotein E–deficient (
Apoe
−/−
) mice fed an atherogenic diet, antibody blockade of JAM-C significantly reduced neointimal hyperplasia after wire injury of carotid arteries without altering medial area and decreased neointimal macrophage but not smooth muscle cell (SMC) content. An increased expression of JAM-C was detected in colocalization with luminal SMCs 1 day after injury and neointimal SMCs after 3 weeks. Blocking JAM-C inhibited monocytic cell arrest and leukocyte adhesion to carotid arteries perfused ex vivo and in vivo. Furthermore, monocyte adhesion to activated coronary artery SMCs under flow conditions in vitro was diminished by blocking JAM-C.

Conclusions—

Our data provide the first evidence for a crucial role of JAM-C in accelerated lesion formation and leukocyte recruitment in atherosclerosis-prone mice.
Lack of Phosphatidylethanolamine
N
-Methyltransferase Alters Plasma VLDL Phospholipids and Attenuates Atherosclerosis in Mice
Authors: Zhao Yang , Su Brian , Jacobs René L. , Kennedy Brian , Francis Gordon A. , Waddington Emma , Brosnan John T. , Vance Jean E. , Vance Dennis E.
Published: June 2009

Objective—

Impaired hepatic phosphatidylcholine (PC) synthesis lowers plasma lipids. We, therefore, tested the hypothesis that lack of phosphatidylethanolamine N-methyltransferase (PEMT), a hepatic enzyme catalyzing PC biosynthesis, attenuates the development of atherosclerosis.

Methods and Results—

Mice deficient in both PEMT and low-density lipoprotein receptors (

Pemt
−/−
/Ldlr
−/−

mice) were fed a high-fat/high-cholesterol diet for 16 weeks. Atherosclerotic lesion area was ≈80% lower (
P
<0.01) in

Pemt
−/−
/Ldlr
−/−

mice than in

Pemt
+/+
/Ldlr
−/−

mice, consistent with the atheroprotective plasma lipoprotein profile (ie, significant reduction in very low–density lipoprotein [VLDL]/intermediate-density lipoprotein/low-density lipoprotein–associated phospholipids [≈45%], triacylglycerols [≈65%], cholesterol [≈58%], and cholesteryl esters [≈68%]). Plasma apoB was decreased by 40% to 60%, whereas high-density lipoprotein levels were not altered. In addition, PEMT deficiency reduced plasma homocysteine by 34% to 52% in

Pemt
−/−
/Ldlr
−/−

mice. The molar ratio of PC/phosphatidylethanolamine in nascent VLDLs produced by

Pemt
−/−
/Ldlr
−/−

mice was lower than in VLDLs in

Pemt
+/+
/Ldlr
−/−

mice. Furthermore, deletion of PEMT modestly reduced hepatic VLDL secretion in

Ldlr
−/−

mice and altered the rate of VLDL clearance from plasma.

Conclusion—

This is the first report showing that inhibition of hepatic phospholipid biosynthesis attenuates atherosclerosis.
Lysophosphatidylcholine Activates a Novel PKD2-Mediated Signaling Pathway That Controls Monocyte Migration
Authors: Tan Mingqi , Hao Feng , Xu Xuemin , Chisolm Guy M. , Cui Mei-Zhen
Published: June 2009

Objective—

Monocyte activation and migration are crucial events in the development of atherosclerosis and other inflammatory diseases. This study examined the role of protein kinase D (PKD) in monocyte migration.

Method and Results—

PKD2 is the predominant isoform of PKD expressed in monocytic THP-1 cells and primary human monocytes. Lysophosphatidylcholine (lysoPC), a prominent component of oxidized low-density lipoprotein, induces rapid and marked PKD activation in these cells. Using multiple approaches, including dominant-negative mutants and small interfering RNA knock-down, we found that lysoPC-induced PKD2 activation was required for the activation of both ERK and p38 MAPK. p38 MAPK mediation of lysoPC-induced monocytic cell migration was reported previously; our results reveal that the lysoPC-induced PKD2-p38 pathway controls monocyte migration.

Conclusions—

This study provides the first evidence that (1) lysoPC activates PKD, (2) PKD2 has a novel role in p38 activation, and (3) the PKD2-activated p38 pathway is responsible for lysoPC-induced migration of THP-1 cells and human monocytes. Thus, PKD is a novel and functional intracellular regulator in both lysoPC signaling and monocyte migration. These results suggest a new role for PKD2 in the development of atherosclerosis and other inflammatory diseases.
Dissociation of Pentameric to Monomeric C-Reactive Protein on Activated Platelets Localizes Inflammation to Atherosclerotic Plaques
Authors: Eisenhardt Steffen U. , Habersberger Jonathon , Murphy Andrew , Chen Yung-Chih , Woollard Kevin J. , Bassler Nicole , Qian Hongwei , von zur Muhlen Constantin , Hagemeyer Christoph E. , Ahrens Ingo , Chin-Dusting Jaye , Bobik Alex , Peter Karlheinz
Published: June 2009

C-reactive protein (CRP) is a predictor of cardiovascular risk. It circulates as a pentamer (pentameric CRP) in plasma. The in vivo existence of monomeric (m)CRP has been postulated, but its function and source are not clear. We show that mCRP is deposited in human aortic and carotid atherosclerotic plaques but not in healthy vessels. pCRP is found neither in healthy nor in diseased vessels. As source of mCRP, we identify a mechanism of dissociation of pCRP to mCRP. We report that activated platelets, which play a central role in cardiovascular events, mediate this dissociation via lysophosphatidylcholine, which is present on activated but not resting platelets. Furthermore, the dissociation of pCRP to mCRP can also be mediated by apoptotic monocytic THP-1 and Jurkat T cells. The functional consequence is the unmasking of proinflammatory effects of CRP as demonstrated in experimental settings that are pathophysiologically relevant for atherogenesis: compared to pCRP, mCRP induces enhanced monocyte chemotaxis; monocyte activation, as determined by conformational change of integrin Mac-1; generation of reactive oxygen species; and monocyte adhesion under static and physiological flow conditions. In conclusion, we demonstrate mCRP generation via pCRP dissociation on activated platelets and H
2
O
2
-treated apoptotic THP-1 and Jurkat T cells, thereby identifying a mechanism of localized unmasking of the proinflammatory properties of CRP. This novel mechanism provides a potential link between the established cardiovascular risk marker, circulating pCRP, and localized platelet-mediated inflammatory and proatherogenic effects.
Avoidance of Transient Cardiomyopathy in Cardiomyocyte-Targeted Tamoxifen-Induced MerCreMer Gene Deletion Models
Authors: Koitabashi Norimichi , Bedja Djahida , Zaiman Ari L. , Pinto Yigal M. , Zhang Manling , Gabrielson Kathleen L. , Takimoto Eiki , Kass David A.
Published: June 2009

Cardiac myocyte targeted MerCreMer transgenic mice expressing tamoxifen-inducible Cre driven by the α-myosin heavy chain promoter are increasingly used to control gene expression in the adult heart. Here, we show tamoxifen-mediated MerCreMer (MCM) nuclear translocation can induce severe transient dilated cardiomyopathy in mice with or without loxP transgenes. The cardiomyopathy is accompanied by marked reduction of energy/metabolism and calcium-handling gene expression (eg, PGC1-α, peroxisome proliferator-activated α, SERCA2A), all fully normalized with recovery. MCM-negative/flox-positive controls display no dysfunction with tamoxifen. Nuclear Cre translocation and equally effective gene knockdown without cardiomyopathy is achievable with raloxifene, suggesting toxicity is not simply from Cre. Careful attention to controls, reduced tamoxifen dosing and/or use of raloxifene is advised with this model.
L-Type Calcium Channel Blockers Exert an Antiinflammatory Effect by Suppressing Expression of Plasminogen Receptors on Macrophages
Authors: Das Riku , Burke Tim , Van Wagoner David R. , Plow Edward F.
Published: June 2009

L-type Ca
2+
channel (LTCC) blockers, represented by amlodipine and verapamil, are widely used antihypertensive drugs that also have antiinflammatory activities. Plasminogen (Plg) is an important mediator of macrophage recruitment, and this role depends on its interaction with Plg receptors (Plg-Rs). Plg-Rs include histone 2B, α-enolase, annexin 2, and p11, all proteins which lack signal sequences for cell surface export. When human or murine monocytoid cells were induced to differentiate into macrophages, their Plg binding and Plg-R expression increased by 4-fold. These changes were suppressed by pretreatment with verapamil and amlodipine. Expression of the Ca
v
1.2 LTCC pore subunit was induced in differentiated macrophages, and siRNA against this subunit suppressed the upregulation of Plg binding and Plg-Rs. In vivo, amlodipine and verapamil suppressed peritoneal macrophage recruitment in response to thioglycollate by >60% at doses that did not affect blood pressure. In drug-treated animals, macrophages migrated into but not through the peritoneal membrane tissue and showed reduced surface expression of Plg-Rs. These findings demonstrate that Plg-R expression on macrophages is dependent on Ca
v
1.2 LTCC subunit expression. Suppression of Plg-Rs may contribute to the antiinflammatory effects of the widely used LTCC blockers.
Glycemic Status Underlies Increased Arterial Stiffness and Impaired Endothelial Function in Migrant South Asian Stroke Survivors Compared to European Caucasians
Authors: Gunarathne Ashan , Patel Jeetesh V. , Kausar Shahid , Gammon Brian , Hughes Elizabeth A. , Lip Gregory Y.H.
Published: June 2009

Background—

The pathophysiology of an increased risk of cerebrovascular disease mortality among South Asians (SA) remains unclear. Indices of arterial stiffness and endothelial dysfunction are independent markers of vascular disease, having both prognostic and diagnostic implications. We hypothesized that there are ethnic variations in indices of arterial stiffness and endothelial dysfunction between SA and European Caucasian (EC) stroke patients, which may underline a poorer prognosis in the former, and further investigated promoters of vessel wall abnormalities.

Methods—

Using a cross-sectional approach, a total of 100 SA stroke survivors were prospectively recruited from the ongoing West Birmingham Stroke Project. Indices of vessel wall characteristics (arterial stiffness and endothelial function [change in reflective index]) were measured noninvasively using the digital volume pulse analysis technique in a temperature-controlled environment, using a direct standardized approach. SA stroke subjects were compared to 60 EC stroke survivors, 60 SA with risk factors, and 73 healthy controls.

Results—

Among stroke patients, both ethnic groups were comparable for cardiovascular risk profile, except for more diabetes mellitus in SA (
P
=0.007) subjects and a higher prevalence of atrial fibrillation in EC (
P
=0.04) subjects. According to the TOAST and Bamford classifications, SA subjects had more small vessel (
P
=0.04) and lacunar infarctions (
P
=0.01). SA subjects had higher measurements of arterial stiffness (
P
<0.001) and impaired endothelial-dependent vascular function (change in reflective index %;
P
<0.001). On univariate analysis, endothelial function was negatively correlated with fasting plasma glucose (
r
=−0.4;
P
<0.001) and total cholesterol level (
r
=−0.2;
P
<0.001). On multivariate analysis, glycemic status was independently associated with impaired endothelial function (
P
=0.008) and increased arterial stiffness (
P
<0.001) among SA subjects.

Conclusion—

SA stroke survivors had more small vessel disease-related cerebrovascular events compared to EC subjects. Underlying glycemic status in SA subjects had an adverse impact on the vascular system, leading to abnormal vessel wall characteristics.
Mast Cells Are Early Responders After Hypoxia-Ischemia in Immature Rat Brain
Authors: Jin Yuxuan , Silverman Ann J. , Vannucci Susan J.
Published: June 2009

Background and Purpose—

Perinatal hypoxia-ischemia (HI) produces acute and prolonged inflammation of the brain. Mast cells (MCs), numerous in the pia and CNS of neonatal rats, can initiate inflammation attributable to preformed mediators. MCs contribute to HI brain damage in the neonatal rat; MC stabilization protects through 48 hours of reperfusion. Here we hypothesize that HI induces early MC migration, activation, and release of proinflammatory molecules.

Methods—

HI was induced by right CCA ligation and 75 minutes 8% oxygen. Histochemistry and immunocytochemistry described the time course of early cellular changes in the CNS. For neuroprotection by MC stabilization, pups were treated with Cromolyn (CR) during the initial 24 hours post-HI; brains were examined through 4 weeks.

Results—

Brain MC number and activation were elevated in ipsilateral hemisphere immediately after HI (
P
<0.05), before detection of cleaved caspase-3 in neurons (NeuN+; 2 hours post-HI), astroglial activation (GFAP+ with swollen cell body, 4 hours post-HI), or microglial activation (OX42+, 4 hours post-HI). TNF-α-positive MCs were present in a subpopulation of MCs in control animals and the percent of TNF-α MCs increased dramatically ipsilaterally immediately after HI (
P
<0.01). Microglial TNF-α was evident at 4 hours; endothelial cells had no detectable TNF-α until 48 hours post-HI. Cromolyn prevented MC migration, reduced brain damage/neuronal loss, glial activation, and brain atrophy through 4 weeks of recovery (
P
<0.05).

Conclusions—

MCs are early responders to HI in neonatal brain. MC stabilization provides lasting protection and suggests a new target for therapeutic interventions.
Single Limb Exercise Induces Femoral Artery Remodeling and Improves Blood Flow in the Hemiparetic Leg Poststroke
Authors: Billinger Sandra A. , Gajewski Byron J. , Guo Lisa X. , Kluding Patricia M.
Published: June 2009

Background and Purpose—

After stroke, individuals have decreased mobility of the hemiparetic leg, which demands less muscle oxygen consumption; thus, blood flow decreases. The purpose of this study was to determine the effect of single limb exercise (SLE) on femoral artery blood flow, diameter, and peak flow velocity in the hemiparetic leg after stroke.

Methods—

Twelve individuals (60.6±14.5 years of age; 5 male) with chronic stroke (69.1±82.2 months; 5 with right-sided hemiparesis) participated in the study. The intervention consisted of a SLE knee extension/flexion protocol 3 times per week for 4 weeks. Using Doppler ultrasound, bilateral femoral artery blood flow, diameter, and peak flow velocity were assessed at baseline, after 2 weeks, and after 4 weeks of SLE.

Results—

Using repeated-measures analysis of variance, femoral artery blood flow, arterial diameter, and blood flow velocity in the hemiparetic limb were significantly improved (
P
<0.0001) after the SLE. No significant changes occurred in the nontrained limb for any outcome measures.

Conclusions—

These data suggest that a 4-week SLE training program that increases muscular activity in the hemiparetic limb improves femoral artery blood flow, diameter, and peak velocity. SLE may be an important training strategy in stroke rehabilitation to minimize the vascular changes that occur poststroke due to decreased activity of the hemiparetic limb.
Does ABCD
2
Score Below 4 Allow More Time to Evaluate Patients With a Transient Ischemic Attack?
Authors: Amarenco Pierre , Labreuche Julien , Lavallée Philippa C. , Meseguer Elena , Cabrejo Lucie , Slaoui Tarik , Guidoux Céline , Olivot Jean-Marc , Abboud Halim , Lapergue Bertrand , Klein Isabelle F. , Mazighi Mikael , Touboul Pierre-Jean
Published: June 2009

Background and Purpose—

The National Institute for Clinical Excellence (NICE) recommends that patients with a transient ischemic attack and ABCD
2
score ≥4 and those with >2 transient ischemic attacks within 1 week be admitted for urgent complete etiologic evaluation within 24 hours and that those with an ABCD
2
score <4 be evaluated less urgently within 1 week.

Methods—

Using data from 1176 patients with a definite or possible transient ischemic attack or minor stroke included in the SOS-TIA registry (January 2003 to June 2007), we studied the usefulness of the conventional ABCD
2
score cutoff as well as the NICE criteria for urgent admission to a stroke unit defined as presence of symptomatic internal carotid artery stenosis ≥50%, symptomatic intracranial artery stenosis ≥50%, or major cardiac source of embolism.

Results—

Among 697 patients with an ABCD
2
score <4, 20% required immediate consideration for emergency treatment (eg, symptomatic internal carotid stenosis ≥50% in 9.1% of patients, symptomatic intracranial stenosis in 5.0%, atrial fibrillation in 5.9%, other major cardiac source of embolism in 2.1%) in comparison to 31.6% of 497 patients with an ABCD
2
score ≥4. The sensitivity and specificity of ABCD
2
score ≥4 or NICE criteria for discriminating between patients requiring admission or not were <62% with low positive predictive values (<30%) and high negative predictive values (≥80%).

Conclusions—

One in 5 patients with an ABCD
2
score <4 had high-risk disease requiring urgent treatment decision-making. When triaging on an ABCD
2
score, we recommend adding systematic carotid ultrasound (or a default angiographic CT scan) and electrocardiography within 24 hours before postponing complete transient ischemic attack evaluation.
Withdrawal of Statins and Risk of Subarachnoid Hemorrhage
Authors: Risselada Roelof , Straatman Huub , van Kooten Fop , Dippel Diederik W.J. , van der Lugt Aad , Niessen Wiro J. , Firouzian Azadeh , Herings Ron M.C. , Sturkenboom Miriam C.J.M.
Published: June 2009

Background and Purpose—

Vascular endothelium, which can be affected by statins, is believed to play a substantial role in subarachnoid hemorrhage (SAH). Our objective was to estimate the association between use and withdrawal of statins and the risk of SAH.

Methods—

We conducted a population-based case–control study within the PHARMO database. A case was defined as a person hospitalized for SAH (ICD-9-CM code 430) in the period January 1, 1998 to December 31, 2006. Ten randomly chosen controls were matched to each case on age, gender, and calendar date.

Results—

During the study period 1004 incident cases of SAH were identified. Current use of statins did not significantly decrease the risk of SAH (OR=0.77, 95% CI 0.55 to 1.07). The odds ratio for recent withdrawal compared to nonusers was 1.62 (95% CI 0.96 to 2.73). Compared to current use, recent withdrawal was associated with an increased risk of SAH (OR=2.34, 95% CI 1.35 to 4.05). Interaction analysis showed that the effect of statin withdrawal was highest in patients who had also recently stopped antihypertensive drugs (OR=6.77, 95% CI 2.10 to 21.8).

Conclusions—

Current use of statins seems to lower the risk of SAH, although the reduction was not significant in new users. Statin withdrawal increased the risk of SAH by a factor 2, even more in patients who had also recently stopped their antihypertensive treatment.
Coiling of Intracranial Aneurysms
Authors: Ferns Sandra P. , Sprengers Marieke E.S. , van Rooij Willem Jan , Rinkel Gabriël J.E. , van Rijn Jeroen C. , Bipat Shandra , Sluzewski Menno , Majoie Charles B.L.M.
Published: June 2009

Background and Purpose—

The proportion of incompletely occluded aneurysms after coiling varies widely between studies. To assess overall outcome of coiling, we systematically reviewed the literature to determine initial occlusion, reopening, and retreatment rates of coiled aneurysms according to predefined criteria and subgroups.

Methods—

We searched PubMed and EMBASE (January 1999 to September 2008) for studies of >50 coiled aneurysms. Two reviewers independently extracted data. We grouped studies reporting on only ruptured aneurysms, posterior circulation aneurysms, and studies with large proportions of aneurysms >10 mm to assess possible determinants for incomplete occlusion, reopening, and retreatment.

Results—

Forty-six studies totalling 8161 coiled aneurysms met inclusion criteria. Immediately after coiling, 91.2% (95% CI, 90.6% to 91.9%) of the aneurysms were adequately occluded. Aneurysm reopening occurred in 20.8% (95% CI, 19.8% to 21.9%) and retreatment was performed in 10.3% (95% CI, 9.5% to 11.0%). Reopening rate was lower in studies reporting on ruptured aneurysms only compared with all studies (11.4% versus 20.8%; relative risk, 0.55; 95% CI, 0.47 to 0.64) and higher in studies focusing on posterior circulation aneurysms compared with studies with >85% anterior circulation aneurysms (22.5% versus 15.5%; relative risk, 1.5; 95% CI,1.2 to 1.7). Regression analysis showed higher retreatment rates with increasing proportion of aneurysms >10 mm (β=0.252; 95% CI, 0.073 to 0.432). We could not find a relation between reopening and type of coils used.

Conclusion—

At follow-up, one fifth of all coiled intracranial aneurysms shows reopening of which half is retreated. Possible risk factors for aneurysm reopening are location in the posterior circulation and size >10 mm. To confirm our findings, a meta-analysis on individual well-reported patient data is desirable.
Proapoptotic Role of Human Growth and Transformation-Dependent Protein in the Developing Rat Brain After Hypoxia-Ischemia
Authors: Qu Yi , Mao Meng , Zhao Fengyan , Zhang Lin , Mu Dezhi
Published: June 2009

Background and Purpose—

Human growth and transformation-dependent protein (HGTD-P) is a new proapoptotic protein and an effector of cell death induced by hypoxia-ischemia (HI). The function of HGTD-P has been investigated in human prostate cancer cells and mouse neurons cultured in vitro. However, whether HGTD-P is involved in regulating the apoptosis of rat neurons is not clear, and the relevance of HGTD-P in HI animal models is still unknown. Therefore, in the present study, we tried to elucidate the role that HGTD-P plays in apoptosis of rat neurons subjected to HI, both in culture and in the developing rat brain in vivo.

Methods—

Samples from primary cultured neurons and postnatal day 10 rat brains with HI were collected. RT-PCR, Western blotting, and immunocytochemistry were used to detect the expression and distribution of rat HGTD-P, cleaved caspase 3, and apoptosis- inducing factor (AIF). MTT assay, DAPI, TUNEL, and flowcytometry were used to detect cell viability and apoptosis.

Results—

We found that HI upregulated the mRNA and protein levels of HGTD-P in rat neurons in vitro and in vivo. Antisense oligonucleotides (AS) targeted to HGTD-P inhibited the expression of HGTD-P, thus rescuing neuronal viability and attenuating neuronal apoptosis. In addition, we found that HGTD-P played its proapoptotic role by activating caspase 3 and inducing the translocation of AIF to nuclear.

Conclusions—

Our findings show that HGTD-P plays a proapoptotic role in the developing rat brain after HI and that it may be a potential target in treating HI-induced brain damage.
Summer Severe-Rainfall Frequency Trend and Variability over Ontario, Canada
Authors: Cao Zuohao , Ma Jianmin
Published: June 2009

During the last two decades (1979–2002), there has been an ever-increasing frequency of summer severe-rainfall events over Ontario, Canada. This observed upward trend is robust as demonstrated through the Mann–Kendall test with consideration of removing a lag-1 autoregressive process. It is shown through composite analyses using the NCEP reanalysis data that in the presence of warming conditions the summer severe-rainfall events occur more frequently over Ontario, especially under atmospheric conditions with stronger low-level cyclonic circulations and more precipitable water. Further analyses indicate that over north and central Ontario the summer severe-rainfall frequency is linked with a positive trend of precipitable water whereas over central and south Ontario there is a strong interannual response of summer severe-rainfall frequency to the changes in precipitable water through the variations of air temperature.
The Role of the Sahara Low in Summertime Sahel Rainfall Variability and Change in the CMIP3 Models
Authors: Biasutti M. , Sobel A. H. , Camargo Suzana J.
Published: June 2009

Projections for twenty-first-century changes in summertime Sahel precipitation differ greatly across models in the third Coupled Model Intercomparison Project (CMIP3) dataset and cannot be explained solely in terms of discrepancies in the projected anomalies in global SST.

This study shows that an index describing the low-level circulation in the North Atlantic–African region, namely, the strength of the low-level Saharan low, correlates with Sahel rainfall in all models and at the time scales of both interannual and interdecadal natural variability and of the forced centennial trend.

An analysis of Sahel interannual variability provides evidence that variations in the Sahara low can be a cause, not just a consequence, of variations in Sahel rainfall and suggests that a better understanding of the sources of model discrepancy in Sahel rainfall predictions might be gained from an analysis of the mechanisms influencing changes in the Sahara low.
The Effect of Terrestrial Photosynthesis Down Regulation on the Twentieth-Century Carbon Budget Simulated with the CCCma Earth System Model
Authors: Arora V. K. , Boer G. J. , Christian J. R. , Curry C. L. , Denman K. L. , Zahariev K. , Flato G. M. , Scinocca J. F. , Merryfield W. J. , Lee W. G.
Published: June 2009

The simulation of atmospheric–land–ocean CO2 exchange for the 1850–2000 period offers the possibility of testing and calibrating the carbon budget in earth system models by comparing the simulated changes in atmospheric CO2 concentration and in land and ocean uptake with observation-based information. In particular, some of the uncertainties associated with the treatment of land use change (LUC) and the role of down regulation in affecting the strength of CO2 fertilization for terrestrial photosynthesis are assessed using the Canadian Centre for Climate Modelling and Analysis Earth System Model (CanESM1). LUC emissions may be specified as an external source of CO2 or calculated interactively based on estimated changes in crop area. The evidence for photosynthetic down regulation is reviewed and an empirically based representation is implemented and tested in the model. Four fully coupled simulations are performed: with and without terrestrial photosynthesis down regulation and with interactively determined or specified LUC emissions. Simulations without terrestrial photosynthesis down regulation yield 15–20 ppm lower atmospheric CO2 by the end of the twentieth century, compared to observations, regardless of the LUC approach used because of higher carbon uptake by land. Implementation of down regulation brings simulated values of atmospheric CO2 and land and ocean carbon uptake closer to observation-based values. The use of specified LUC emissions yields a large source in the tropics during the 1981–2000 period, which is inconsistent with studies suggesting the tropics to be near-neutral or small carbon sinks. The annual cycle of simulated global averaged CO2, dominated by the Northern Hemisphere terrestrial photosynthesis and respiration cycles, is reasonably well reproduced, as is the latitudinal distribution of CO2 and the dependence of interhemispheric CO2 gradient on fossil fuel emissions. The empirical approach used here offers a reasonable method of implementing down regulation in coupled carbon–climate models in the absence of a more explicit biogeochemical representation.
Gap-Leaping Vortical Currents
Authors: McDonald N. Robb , Johnson E. R.
Published: June 2009

A one-parameter family of exact solutions describing the bifurcation of a steady two-dimensional current with uniform vorticity near a gap in a thin barrier is found. The unsteady evolution of source-driven flows toward these steady states is studied using a version of contour dynamics, appropriately modified to take into account the presence of a barrier with a single gap. It is shown that some of the steady solutions are realizable as large-time limits of the source-driven flows, although some are not owing to persistent eddy-shedding events in the vicinity of the gap. For the special case when there is zero net flux through the gap, numerical experiments show that the through-gap flux of vortical fluid increases with the width of the gap and that this flux approaches a steady limit with time.
Synoptic- and Frontal-Scale Influences on Tropical Transition Events in the Atlantic Basin. Part II: Tropical Transition of Hurricane Karen
Authors: Hulme Andrew L. , Martin Jonathan E.
Published: June 2009

A finescale simulation of the tropical transition of Atlantic Hurricane Karen in October 2001 is examined to determine the processes leading to the development of upshear convection and its effects on the process of tropical transition. The analysis shows that, as in marine extratropical cyclones, the area upshear of the pretransition cyclone is characterized by reduced stability. Lower-tropospheric frontogenesis leads to an intense burst of convection there and instigates three important processes that combine to produce a full-fledged tropical cyclone. First, the convection generates intense low-level vorticity on the western half of the cyclone, which quickly dominates the cyclone’s vorticity field eventually organizing the circulation into a small-scale, intense vortex. Second, the diabatically enhanced circulation hastens the isolation of the cyclone’s developing warm core by intensifying cold air advection on the northern and western sides of the storm and by placing evaporatively cooled air into the boundary layer to the south of the cyclone. Third, upshear convection vertically redistributes potential vorticity (PV) from the tropopause to the surface and introduces a component to the upper-level winds, which advects strong, shear-inducing PV gradients away from the column above the cyclone. These three processes transform the initial extratropical cyclone into a frontless vortex with tropical storm–force winds and a warm core in a low-shear environment. These features are sufficient, given a warm enough ocean surface, to allow self-amplification of the storm as a tropical cyclone.

The results further blur the distinction between tropical and extratropical cyclones as many of the processes identified as important to transition are similar to those that characterize ordinary marine cyclones and the extratropical occlusion process with the key distinctions being that here the convection is stronger and the initial upper-level feature is weaker. Thus, tropical transition of strong extratropical precursors follows the canonical midlatitude cyclone life cycle with upshear convection serving as the catalyst that both induces and organizes processes that favor tropical cyclogenesis in the postmature phase.
Dynamical Forecast of Inter–El Niño Variations of Tropical SST and Australian Spring Rainfall
Authors: Lim Eun-Pa , Hendon Harry H. , Hudson Debra , Wang Guomin , Alves Oscar
Published: June 2009

The relationship between variations of Indo-Pacific sea surface temperatures (SSTs) and Australian springtime rainfall over the last 30 years is investigated with a focus on predictability of inter–El Niño variations of SST and associated rainfall anomalies. Based on observed data, the leading empirical orthogonal function (EOF) of Indo-Pacific SST represents mature El Niño conditions, while the second and fourth modes depict major east–west shifts of individual El Niño events. These higher-order EOFs of SST explain more rainfall variance in Australia, especially in the southeast, than does the El Niño mode. Furthermore, intense springtime droughts tend to be associated with peak warming in the central Pacific, as captured by EOFs 2 and 4, together with warming in the eastern Pacific as depicted by EOF1.

The ability to predict these inter–El Niño variations of SST and Australian rainfall is assessed with the Australian Bureau of Meteorology dynamical coupled model seasonal forecast system, the Predictive Ocean and Atmospheric Model for Australia (POAMA). A 10-member ensemble of 9-month hindcasts was generated for the period 1980–2006. For the September–November season, the leading 2 EOFs of SST are predictable with lead times of 3–6 months, while SST EOF4 is predictable out to a lead time of 1 month. The teleconnection between the leading EOFs of SST and Australian rainfall is also well depicted in the model. Based on this ability to predict major east–west variations of El Niño and the teleconnection to Australian rainfall, springtime rainfall over eastern Australia, and major drought events are predictable up to a season in advance.