bluuebunny/crossref_metadata_2025 huggingface dataset:
When energy balance is maintained, exercise does not induce negative fat balance in lean sedentary, obese sedentary, or lean endurance-trained individuals
Authors: Melanson Edward L. , Gozansky Wendolyn S. , Barry Daniel W. , MacLean Paul S. , Grunwald Gary K. , Hill James O.
Published: October 2009

Fat oxidation during exercise is increased by endurance training, and evidence suggests that fat oxidation during exercise is impaired in obesity. Thus the primary aim of this study was to compare the acute effects of exercise on 24-h fat oxidation and fat balance in lean sedentary [LS, n = 10, body mass index (BMI) = 22.5 ± 6.5 kg/m2], lean endurance-trained (LT, n = 10, BMI = 21.2 ± 1.2 kg/m2), and obese sedentary (OS, n = 7, BMI = 35.5 ± 4.4 kg/m2) men and women. Twenty-four-hour energy expenditure and substrate oxidation were measured under sedentary (control; CON) and exercise (EX) conditions while maintaining energy balance. During EX, subjects performed 1 h of stationary cycling at 55% of aerobic capacity. Twenty-four-hour fat oxidation did not differ on the CON or EX day in LS (43 ± 9 vs. 29 ± 7 g/day, respectively), LT (53 ± 8 vs. 42 ± 5 g/day), or OS (58 ± 7 vs. 80 ± 9 g/day). However, 24-h fat balance was significantly more positive on EX compared with CON ( P < 0.01). Twenty-four-hour glucose, insulin, and free fatty acid (FFA) profiles were similar on the EX and CON days, but after consumption of the first meal, FFA concentrations remained below fasting levels for the remainder of the day. These data suggest that when exercise is performed with energy replacement (i.e., energy balance is maintained), 24-h fat oxidation does not increase and in fact, may be slightly decreased. It appears that the state of energy balance is an underappreciated factor determining the impact of exercise on fat oxidation.
Sequence Variants in BMPR2 and Genes Involved in the Serotonin and Nitric Oxide Pathways in Idiopathic Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension: Relation to Clinical Parameters and Comparison with Left Heart Disease
Authors: Ulrich Silvia , Szamalek-Hoegel Justyna , Hersberger Martin , Fischler Manuel , Garcia Jesus Solera , Huber Lars C. , Grünig Ekkehard , Janssen Bart , Speich Rudolf
Published: October 2009

Background: Idiopathic pulmonary arterial hypertension (IPAH) and chronic thromboembolic pulmonary hypertension (CTEPH) share important pathogenic and clinical features. BMPR2 mutations are important in the pathogenesis of IPAH, but little is known about the genetic background in CTEPH. Objective: To search for mutations and polymorphisms in genes involved in the BMPR2, serotonin and nitric oxide pathways possibly associated with pulmonary and cardiac disorders in IPAH and CTEPH. Methods: In a cohort of Swiss patients with IPAH (n = 16) and CTEPH (n = 16), and in 24 controls with left heart disease without PH, polymorphisms in the BMPR2, 5-HHT, 5-HTR-2A and eNOS genes were analyzed and correlated with various clinical, functional and hemodynamic parameters. Results: We found a BMPR2 missense mutation in a patient with coronary artery disease (CAD) without PH but no BMPR2 mutations in our collective with late-onset sporadic PH. In patients with polymorphic variants of the BMPR2 gene, the number of blood platelets and oxygen saturation were increased. The c.600A→C synonymous variant was associated with worse exercise capacity and decreased quality of life in PH. We found no significant differences for any measured parameter according to the eNOS, 5-HTR2A and the 5-HTT polymorphisms, although there was a higher allelic frequency of the 5-HTT long variant in IPAH than in CTEPH and controls. Conclusion: Our first report of a BMPR2 mutation in a patient with CAD without PH is interesting and warrants further investigation. Our study may reflect the clinical status and genetic background in a typical PH cohort as seen in a single tertiary care referral center.
Efficacy of a Single Educative Intervention in Patients with Chronic Plaque Psoriasis
Authors: Lora Viviana , Gisondi Paolo , Calza Anna , Zanoni Mauro , Girolomoni Giampiero
Published: October 2009

Background: An effective patient-physician relationship is important in the management of psoriatic patients. Objective: Our purpose was to investigate the efficacy of an educational intervention for patients with psoriasis in improving disease knowledge and attitude towards physicians and systemic treatments. Methods: The intervention consisted of a single, 2-hour educational programme conducted either by a dermatologist or by a dermatologist and a psychologist. Information on psoriasis and its treatment was given. A questionnaire concerning knowledge about psoriasis was administered before and after the programme, and after 6 months. Results: 123 patients were enrolled. They reported a high degree of satisfaction with the intervention, improvement in knowledge about the disease and a better attitude towards therapy. After 6 months a better knowledge about the disease and a higher attitude to treatment were retained. Conclusions: A single educational intervention may be helpful in improving psoriasis knowledge and give psychological relief to patients.
Anthropometric Measures of Obesity and Risk of Venous Thromboembolism
Authors: Borch Knut H. , Brækkan Sigrid K. , Mathiesen Ellisiv B. , Njølstad Inger , Wilsgaard Tom , Størmer Jan , Hansen John-Bjarne
Published: October 2009

Objectives—

The purpose of this study was to assess the impact of various obesity measures on identification of subjects at risk and their respective risk estimates for VTE in a prospective population-based study.

Methods and Results—

Measures of body composition such as body mass index (BMI), waist circumference (WC), hip circumference (HC), and waist-hip ratio (WHR) were registered in 6708 subjects aged 25 to 84 years, who participated in the Tromsø Study (1994–1995). Incident VTE-events were registered during follow-up until September 1, 2007. There were 222 VTE-events during a median of 12.3 years of follow-up. All measures of obesity exhibited significantly increased HR for VTE in multivariable models with highest risk estimates for WC in both genders. The risk of VTE increased across quartiles of BMI, WC, and HC in both genders, but not for WHR. WC identified more subjects at risk using established criteria for obesity. WC had the highest area under the curve in both genders in ROC analysis, and WC above ROC-derived cut-off values (WC ≥85 cm in women and ≥95 cm in men) were associated with HRs of 1.92 (95% CI: 1.05 to 3.48) in women and 2.78 (95% CI: 1.47 to 5.27) in men.

Conclusions—

Our findings indicate that WC is the preferable anthropometric measure of obesity to identify subjects at risk and to predict risk of VTE.
Bone Marrow AT
1
Augments Neointima Formation by Promoting Mobilization of Smooth Muscle Progenitors via Platelet-Derived SDF-1α
Authors: Yokoi Hirokazu , Yamada Hiroyuki , Tsubakimoto Yoshinori , Takata Hiroki , Kawahito Hiroyuki , Kishida Sou , Kato Taku , Matsui Akihiro , Hirai Hideyo , Ashihara Eishi , Maekawa Taira , Iwai Masaru , Horiuchi Masatsugu , Ikeda Kouji , Takahashi Tomosaburo , Okigaki Mitsuhiko , Matsubara Hiroaki
Published: October 2009

Objectives—

Bone marrow (BM)-derived endothelial progenitor cells (EPCs) and vascular smooth muscle progenitor cells (VPCs) contribute to neointima formation, whereas the angiotensin II (Ang II) type 1 receptor (AT
1
)-mediated action on BM-derived progenitors remains undefined.

Methods and Results—

A wire-induced vascular injury was performed in the femoral artery of BM-chimeric mice whose BM was repopulated with AT
1
-deficient (BM-Agtr1
−/−
) or wild-type (BM-Agtr1
+/+
) cells. Neointima formation was profoundly reduced by 38% in BM-Agtr1
−/−
mice. Although the number of circulating EPCs (Sca-1
+
Flk-1
+
) and extent of reendothelialization did not differ between the 2 groups, the numbers of both circulating VPCs (c-Kit
−
Sca-1
+
Lin
−
) and tissue VPCs (Sca-1
+
CD31
−
) incorporated into neointima were markedly decreased in BM-Agtr1
−/−
mice. The accumulation of aggregated platelets and their content of stromal cell–derived factor-1α (SDF-1α) were significantly reduced in BM-Agtr1
−/−
mice, accompanied by a decrease in the serum level of SDF-1α. Thrombin-induced platelets aggregation was dose-dependently inhibited (45% at 0.1 IU/mL,
P
<0.05) in Agtr1
−/−
platelets compared with Agtr1
+/+
platelets, accompanied by the reduced expression and release of SDF-1α.

Conclusions—

The BM-AT
1
receptor promotes neointima formation by regulating the mobilization and homing of BM-derived VPCs in a platelet-derived SDF-1α–dependent manner without affecting EPC-mediated reendothelialization.
JAK/STAT Signaling Pathway Regulates Nox1 and Nox4-Based NADPH Oxidase in Human Aortic Smooth Muscle Cells
Authors: Manea Adrian , Tanase Laurentia Irina , Raicu Monica , Simionescu Maya
Published: October 2009

Objective—

Oxidative stress mediated by Nox1- and Nox4-based NADPH oxidase (Nox) plays a key role in vascular diseases. The molecular mechanisms involved in the regulation of Nox are not entirely elucidated. Because JAK/STAT regulates many genes linked to inflammation, cell proliferation, and differentiation, we questioned whether this pathway is involved in the regulation of Nox1 and Nox4 in human aortic smooth muscle cells (SMCs).

Methods and Results—

Cultured SMCs were exposed to interferon γ (IFNγ) for 24 hours. Using lucigenin-enhanced chemiluminescence and dihydroethidium assays, real-time polymerase chain reaction, and Western blot analysis, we found that JAK/STAT inhibitors significantly diminished the IFNγ-dependent upregulation of Nox activity, Nox1 and Nox4 expression. In silico analysis revealed the presence of highly conserved GAS elements within human Nox1, Nox4, p22phox, p47phox, and p67phox promoters. Transient overexpression of STAT1/STAT3 augmented the promoter activities of each subunit. JAK/STAT blockade reduced the Nox subunits transcription. Chromatin immunoprecipitation demonstrated the physical interaction of STAT1/STAT3 proteins with the predicted GAS elements from Nox1 and Nox4 promoters.

Conclusions—

JAK/STAT is a key regulator of Nox1 and Nox4 in human vascular SMCs. Inhibition of JAK/STAT pathway and the consequent Nox-dependent oxidative stress may be an efficient therapeutic strategy to reduce atherogenesis.
Postmenopausal Hormone Therapy and Risk of Idiopathic Venous Thromboembolism
Authors: Canonico Marianne , Fournier Agnès , Carcaillon Laure , Olié Valérie , Plu-Bureau Geneviève , Oger Emmanuel , Mesrine Sylvie , Boutron-Ruault Marie-Christine , Clavel-Chapelon Françoise , Scarabin Pierre-Yves
Published: October 2009

Objective—

Oral estrogen therapy increases venous thromboembolism risk among postmenopausal women. Although recent data showed transdermal estrogens may be safe with respect to thrombotic risk, the impact of the route of estrogen administration and concomitant progestogens is not fully established.

Methods and Results—

We used data from the E3N French prospective cohort of women born between 1925 and 1950 and biennially followed by questionnaires from 1990. Study population consisted of 80 308 postmenopausal women (average follow-up: 10.1 years) including 549 documented idiopathic first venous thromboembolism. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional models. Compared to never-users, past-users of hormone therapy had no increased thrombotic risk (HR=1.1; 95% CI: 0.8 to 1.5). Oral not transdermal estrogens were associated with increased thrombotic risk (HR=1.7; 95% CI: 1.1 to 2.8 and HR=1.1; 95% CI: 0.8 to 1.8; homogeneity:
P
=0.01). The thrombotic risk significantly differed by concomitant progestogens type (homogeneity:
P
<0.01): there was no significant association with progesterone, pregnanes, and nortestosterones (HR=0.9; 95% CI: 0.6 to 1.5, HR=1.3; 95% CI: 0.9 to 2.0 and HR=1.4; 95% CI: 0.7 to 2.4). However, norpregnanes were associated with increased thrombotic risk (HR=1.8; 95% CI: 1.2 to 2.7).

Conclusions—

In this large study, we found that route of estrogen administration and concomitant progestogens type are 2 important determinants of thrombotic risk among postmenopausal women using hormone therapy. Transdermal estrogens alone or combined with progesterone might be safe with respect to thrombotic risk.
Familial Combined Hyperlipidemia Is Associated With Alterations in the Cholesterol Synthesis Pathway
Authors: van Himbergen Thomas M. , Otokozawa Seiko , Matthan Nirupa R. , Schaefer Ernst J. , Buchsbaum Aaron , Ai Masumi , van Tits Lambertus J.H. , de Graaf Jacqueline , Stalenhoef Anton F.H.
Published: October 2009

Objectives—

Familial combined hyperlipidemia (FCH) is a common familial lipid disorder characterized by increases in plasma total cholesterol, triglyceride, and apolipoprotein B-100 levels. In light of prior metabolic and genetic research, our purpose was to ascertain whether FCH cases had significant abnormalities of plasma markers of cholesterol synthesis and absorption as compared to unaffected kindred members.

Methods and Results—

Plasma levels of squalene, desmosterol, and lathosterol (cholesterol synthesis markers) and campesterol, sitosterol, and cholestanol (cholesterol absorption markers) were measured by gas-liquid chromatography in 103 FCH patients and 240 normolipidemic relatives (NLR). Squalene, desmosterol, and lathosterol levels were 6% (0.078), 31%, (
P
<0.001) and 51% (
P
<0.001) higher in FCH as compared to NLR, and these differences were especially pronounced in women. An interaction with obesity was also noted for a subset of these markers. We did not observe any apparent differences for the cholesterol absorption markers among FCH patients and NLR.

Conclusions—

Our data indicate that both men and women with FCH have alterations in the cholesterol synthesis pathway, resulting in 51% higher levels of lathosterol (and additionally desmosterol in women). Plasma levels of the cholesterol precursor sterol squalene were only slightly increased (6%), suggesting enhanced conversion of squalene to lathosterol in this disorder.
Discoidin Domain Receptor 1 on Bone Marrow–Derived Cells Promotes Macrophage Accumulation During Atherogenesis
Authors: Franco Christopher , Britto Karen , Wong Eric , Hou Guangpei , Zhu Su-Ning , Chen Mian , Cybulsky Myron I. , Bendeck Michelle P.
Published: October 2009

Rationale
:

We described a critical role for the discoidin domain receptor (DDR)1 collagen receptor tyrosine kinase during atherosclerotic plaque development. Systemic deletion of
Ddr1
in
Ldlr
−/−
mice accelerated matrix accumulation and reduced plaque size and macrophage content. However, whether these effects reflected an independent role for macrophage DDR1 during atherogenesis remained unresolved.

Methods
:

In the present study, we performed sex-mismatched bone marrow transplantation using
Ddr1
+/+
;
Ldlr
−/−
and
Ddr1
−/−
;
Ldlr
−/−
mice to investigate the role of macrophage DDR1 during atherogenesis. Chimeric mice with deficiency of DDR1 in bone marrow–derived cells (
Ddr1
−/−→+/+
) or control chimeric mice that received
Ddr1
+/+
;
Ldlr
−/−
marrow (
Ddr1
+/+→+/+
) were fed an atherogenic diet for 12 weeks.

Results
:

We observed a 66% reduction in atherosclerosis in the descending aorta and a 44% reduction in plaque area in the aortic sinus in
Ddr1
−/−→+/+
mice compared to
Ddr1
+/+→+/+
mice. Furthermore, we observed a specific reduction in the number of donor-derived macrophages in
Ddr1
−/−→+/+
plaques, suggesting that bone marrow deficiency of DDR1 attenuated atherogenesis by limiting macrophage accumulation in the plaque. We have also demonstrated that the effects of DDR1 on macrophage infiltration and accumulation can occur at the earliest stage of atherogenesis, the formation of the fatty streak. Deficiency of DDR1 limited the appearance of 5-bromodeoxyuridine–labeled monocytes/macrophages in the fatty streak and resulted in reduced lesion size in
Ldlr
−/−
mice fed a high fat diet for 2 weeks. In vitro studies to investigate the mechanisms involved revealed that macrophages from
Ddr1
−/−
mice had decreased adhesion to type IV collagen and decreased chemotactic invasion of type IV collagen in response to monocyte chemoattractant protein-1.

Conclusions
:

Taken together, our data support an independent and critical role for DDR1 in macrophage accumulation at early and late stages of atherogenesis.
Pressure-Mediated Hypertrophy and Mechanical Stretch Induces IL-1 Release and Subsequent IGF-1 Generation to Maintain Compensative Hypertrophy by Affecting Akt and JNK Pathways
Authors: Honsho Shoken , Nishikawa Susumu , Amano Katsuya , Zen Kan , Adachi Yasushi , Kishita Eigo , Matsui Akihiro , Katsume Asako , Yamaguchi Shinichiro , Nishikawa Kenichiro , Isoda Kikuo , Riches David W.H. , Matoba Satoaki , Okigaki Mitsuhiko , Matsubara Hiroaki
Published: October 2009

Rationale
:

It has been reported that interleukin (IL)-1 is associated with pathological cardiac remodeling and LV dilatation, whereas IL-1β has also been shown to induce cardiomyocyte hypertrophy. Thus, the role of IL-1 in the heart remains to be determined.

Objective
:

We studied the role of hypertrophy signal-mediated IL-1β/insulin-like growth factor (IGF)-1 production in regulating the progression from compensative pressure-mediated hypertrophy to heart failure.

Methods and Results
:

Pressure overload was performed by aortic banding in IL-1β–deficient mice. Primarily cultured cardiac fibroblasts (CFs) and cardiac myocytes (CMs) were exposed to cyclic stretch. Heart weight, myocyte size, and left ventricular ejection fraction were significantly lower in IL-1β–deficient mice (20%, 23% and 27%, respectively) than in the wild type 30 days after aortic banding, whereas interstitial fibrosis was markedly augmented. DNA microarray analysis revealed that IGF-1 mRNA level was markedly (≈50%) decreased in the IL-1β–deficient hypertrophied heart. Stretch of CFs, rather than CMs, abundantly induced the generation of IL-1β and IGF-1, whereas such IGF-1 induction was markedly decreased in IL-1β–deficient CFs. IL-1β released by stretch is at a low level unable to induce IL-6 but sufficient to stimulate IGF-1 production. Promoter analysis showed that stretch-mediated IL-1β activates JAK/STAT to transcriptionally regulate the IGF-1 gene. IL-1β deficiency markedly increased c-Jun N-terminal kinase (JNK) and caspase-3 activities and enhanced myocyte apoptosis and fibrosis, whereas replacement of IGF-1 or JNK inhibitor restored them.

Conclusions
:

We demonstrate for the first time that pressure-mediated hypertrophy and mechanical stretch generates a subinflammatory low level of IL-1β, which constitutively causes IGF-1 production to maintain adaptable compensation hypertrophy and inhibit interstitial fibrosis.
Intravenous Thrombolysis in Stroke Attributable to Cervical Artery Dissection
Authors: Engelter Stefan T. , Rutgers Matthieu P. , Hatz Florian , Georgiadis Dimitrios , Fluri Felix , Sekoranja Lucka , Schwegler Guido , Müller Felix , Weder Bruno , Sarikaya Hakan , Lüthy Regina , Arnold Marcel , Nedeltchev Krassen , Reichhart Marc , Mattle Heinrich P. , Tettenborn Barbara , Hungerbühler Hansjörg J. , Sztajzel Roman , Baumgartner Ralf W. , Michel Patrik , Lyrer Philippe A.
Published: October 2009

Background and Purpose—

Intravenous thrombolysis (IVT) for stroke seems to be beneficial independent of the underlying etiology. Whether this is also true for cervical artery dissection (CAD) is addressed in this study.

Methods—

We used the Swiss IVT databank to compare outcome and complications of IVT-treated patients with CAD with IVT-treated patients with other etiologies (non-CAD patients). Main outcome and complication measures were favorable 3-month outcome, intracranial cerebral hemorrhage, and recurrent ischemic stroke. Modified Rankin Scale score ≤1 at 3 months was considered favorable.

Results—

Fifty-five (5.2%) of 1062 IVT-treated patients had CAD. Patients with CAD were younger (median age 50 versus 70 years) but had similar median National Institutes of Health Stroke Scale scores (14 versus 13) and time to treatment (152.5 versus 156 minutes) as non-CAD patients. In the CAD group, 36% (20 of 55) had a favorable 3-month outcome compared with 44% (447 of 1007) non-CAD patients (OR, 0.72; 95% CI, 0.41 to 1.26), which was less favorable after adjustment for age, gender, and National Institutes of Health Stroke Scale score (OR, 0.50; 95% CI, 0.27 to 0.95;
P
=0.03). Intracranial cerebral hemorrhages (asymptomatic, symptomatic, fatal) were equally frequent in CAD (14% [7%, 7%, 2%]) and non-CAD patients (14% [9%, 5%, 2%];
P
=0.99). Recurrent ischemic stroke occurred in 1.8% of patients with CAD and in 3.7% of non-CAD-patients (
P
=0.71).

Conclusion—

IVT-treated patients with CAD do not recover as well as IVT-treated non-CAD patients. However, intracranial bleedings and recurrent ischemic strokes were equally frequent in both groups. They do not account for different outcomes and indicate that IVT should not be excluded in patients who may have CAD. Hemodynamic compromise or frequent tandem occlusions might explain the less favorable outcome of patients with CAD.
Normal Cortical Energy Metabolism in Migrainous Stroke
Authors: Schulz Ursula G. , Blamire Andrew M. , Davies Paul , Styles Peter , Rothwell Peter M.
Published: October 2009

Background and Purpose—

Previous
31
P–magnetic resonance spectroscopy (
31
P-MRS) studies have shown that cerebral cortical energy metabolism is abnormal in migraine and that cortical energy reserves decrease with increasing severity and duration of aura. Migrainous infarction is a rare complication of migraine with aura, and its pathophysiology is poorly understood. We used
31
P-MRS to determine whether migrainous stroke shows similar interictal abnormalities in cortical energy metabolism as severe, prolonged aura.

Methods—

We used
31
P-MRS to study patients with a diagnosis of either migrainous infarction or migraine with persistent aura without infarction (aura duration >7 days) according to International Headache Society criteria. We compared clinical presentation and metabolite ratios between patient groups. We also studied healthy controls with no history of migraine.

Results—

Patients with persistent aura without infarction had lower phosphocreatine-phosphate (PCr/Pi) ratios (mean±SD, 1.61±0.10) compared with controls (1.94±0.35,
P
=0.011) and with patients with migrainous stroke (1.96±0.16,
P
<0.0001). These differences were present in cortical tissue only. In migrainous stroke patients, the metabolite ratios did not differ significantly from those of controls without migraine.

Conclusions—

The differences in cortical energy reserves between patients with migrainous stroke and in those with migraine with persistent aura suggest that the pathomechanisms of these conditions differ and that migrainous infarction does not simply represent a particularly severe form of migrainous aura. This finding supports the revised International Headache Society criteria, which now distinguish between migrainous infarction and migraine with persistent aura without infarction.
Chagas Disease
Authors: Paixão Leonardo C. , Ribeiro Antonio L. , Valacio Reginaldo A. , Teixeira Antonio L.
Published: October 2009

Background and Purpose—It has been suggested that Chagas disease (CD) and particularly CD cardiomyopathy are independent risk factors for cerebrovascular events. Strong evidence is scarce, cardioembolic and inflammatory mechanisms have been proposed, and most studies lack representative and well-matched controls. We sought to investigate CD, defined by positive serology, as an independent risk factor for stroke, by comparing patients admitted with ischemic stroke with representative control patients with a very similar cardiovascular risk factor profile.

Methods—We performed a case-control study with 101 consecutive stroke patients and 100 consecutive acute coronary syndrome patients admitted to an emergency hospital. CD was investigated in all patients and was confirmed when both immunofluorescence and hemagglutination tests were positive. Clinical, laboratory, and ECG findings were analyzed.

Results—We found that age (P=0.006), female sex (P=0.01), systolic blood pressure (P=0.001), diastolic blood pressure (P=0.03), previous stroke/transient ischemic attack history (P<0.001), atrial fibrillation (P=0.005), other arrhythmias (P=0.05), and CD-positive serology (P=0.002) were more frequent among stroke patients than among patients with acute coronary syndromes. After a multivariable analysis with a backward elimination procedure, previous stroke/transient ischemic attack history (odds ratio=6.98; 95% CI, 2.99 to 16.29), atrial fibrillation (odds ratio=4.52; 95% CI, 1.45 to 14.04), and CD-positive serology (odds ratio=7.17; 95% CI, 1.50 to 34.19) remained independently associated with stroke.

Conclusions—CD seems to be an independent risk factor for ischemic stroke. For patients in or coming from endemic regions, CD should be considered an etiologic or contributing factor for stroke.
Significance of Large Vessel Intracranial Occlusion Causing Acute Ischemic Stroke and TIA
Authors: Smith Wade S. , Lev Michael H. , English Joey D. , Camargo Erica C. , Chou Maggie , Johnston S. Claiborne , Gonzalez Gilberto , Schaefer Pamela W. , Dillon William P. , Koroshetz Walter J. , Furie Karen L.
Published: October 2009

Background and Purpose—

Acute ischemic stroke due to large vessel occlusion (LVO)—vertebral, basilar, carotid terminus, middle and anterior cerebral arteries—likely portends a worse prognosis than stroke unassociated with LVO. Because little prospective angiographic data have been reported on a cohort of unselected patients with stroke and with transient ischemic attack, the clinical impact of LVO has been difficult to quantify.

Methods—

The Screening Technology and Outcome Project in Stroke Study is a prospective imaging-based study of stroke outcomes performed at 2 academic medical centers. Patients with suspected acute stroke who presented within 24 hours of symptom onset and who underwent multimodality CT/CT angiography were approached for consent for collection of clinical data and 6-month assessment of outcome. Demographic and clinical variables and 6-month modified Rankin Scale scores were collected and combined with blinded interpretation of the CT angiography data. The OR of each variable, including occlusion of intracranial vascular segment in predicting good outcome and 6-month mortality, was calculated using univariate and multivariate logistic regression.

Results—

Over a 33-month period, 735 patients with suspected stroke were enrolled. Of these, 578 were adjudicated as stroke and 97 as transient ischemic attack. Among patients with stroke, 267 (46%) had LVO accounting for the stroke and 13 (13%) of patients with transient ischemic attack had LVO accounting for transient ischemic attack symptoms. LVO predicted 6-month mortality (OR, 4.5; 95% CI, 2.7 to 7.3;
P
<0.001). Six-month good outcome (modified Rankin Scale score ≤2) was negatively predicted by LVO (0.33; 0.24 to 0.45;
P
<0.001). Based on multivariate analysis, the presence of basilar and internal carotid terminus occlusions, in addition to National Institutes of Health Stroke Scale and age, independently predicted outcome.

Conclusion—

Large vessel intracranial occlusion accounted for nearly half of acute ischemic strokes in unselected patients presenting to academic medical centers. In addition to age and baseline stroke severity, occlusion of either the basilar or internal carotid terminus segment is an independent predictor of outcome at 6 months.
Biology of Vascular Malformations of the Brain
Authors: Leblanc Gabrielle G. , Golanov Eugene , Awad Issam A. , Young William L. ,   Biology of Vascular Malformations of the Brain NINDS Workshop Collaborators
Published: October 2009

Background and Purpose—

This review discusses recent research on the genetic, molecular, cellular, and developmental mechanisms underlying the etiology of vascular malformations of the brain (VMBs), including cerebral cavernous malformation, sporadic brain arteriovenous malformation, and the arteriovenous malformations of hereditary hemorrhagic telangiectasia.

Summary of Review—

The identification of gene mutations and genetic risk factors associated with cerebral cavernous malformation, hereditary hemorrhagic telangiectasia, and sporadic arteriovenous malformation has enabled the development of animal models for these diseases and provided new insights into their etiology. All of the genes associated with VMBs to date have known or plausible roles in angiogenesis and vascular remodeling. Recent work suggests that the angiogenic process most severely disrupted by VMB gene mutation is that of vascular stabilization, the process whereby vascular endothelial cells form capillary tubes, strengthen their intercellular junctions, and recruit smooth muscle cells to the vessel wall. In addition, there is now good evidence that in some cases, cerebral cavernous malformation lesion formation involves a genetic 2-hit mechanism in which a germline mutation in one copy of a cerebral cavernous malformation gene is followed by a somatic mutation in the other copy. There is also increasing evidence that environmental second hits can produce lesions when there is a mutation to a single allele of a VMB gene.

Conclusions—

Recent findings begin to explain how mutations in VMB genes render vessels vulnerable to rupture when challenged with other inauspicious genetic or environmental factors and have suggested candidate therapeutics. Understanding of the cellular mechanisms of VMB formation and progression in humans has lagged behind that in animal models. New knowledge of lesion biology will spur new translational work. Several well-established clinical and genetic database efforts are already in place, and further progress will be facilitated by collaborative expansion and standardization of these.
Recombinant Human Erythropoietin in the Treatment of Acute Ischemic Stroke
Authors: Ehrenreich Hannelore , Weissenborn Karin , Prange Hilmar , Schneider Dietmar , Weimar Christian , Wartenberg Katja , Schellinger Peter D. , Bohn Matthias , Becker Harald , Wegrzyn Martin , Jähnig Peter , Herrmann Manfred , Knauth Michael , Bähr Mathias , Heide Wolfgang , Wagner Armin , Schwab Stefan , Reichmann Heinz , Schwendemann Günther , Dengler Reinhard , Kastrup Andreas , Bartels Claudia
Published: October 2009

Background and Purpose—

Numerous preclinical findings and a clinical pilot study suggest that recombinant human erythropoietin (EPO) provides neuroprotection that may be beneficial for the treatment of patients with ischemic stroke. Although EPO has been considered to be a safe and well-tolerated drug over 2 decades, recent studies have identified increased thromboembolic complications and/or mortality risks on EPO administration to patients with cancer or chronic kidney disease. Accordingly, the double-blind, placebo-controlled, randomized German Multicenter EPO Stroke Trial (Phase II/III; ClinicalTrials.gov Identifier: NCT00604630) was designed to evaluate efficacy and safety of EPO in stroke.

Methods—

This clinical trial enrolled 522 patients with acute ischemic stroke in the middle cerebral artery territory (intent-to-treat population) with 460 patients treated as planned (per-protocol population). Within 6 hours of symptom onset, at 24 and 48 hours, EPO was infused intravenously (40 000 IU each). Systemic thrombolysis with recombinant tissue plasminogen activator was allowed and stratified for.

Results—

Unexpectedly, a very high number of patients received recombinant tissue plasminogen activator (63.4%). On analysis of total intent-to-treat and per-protocol populations, neither primary outcome Barthel Index on Day 90 (
P
=0.45) nor any of the other outcome parameters showed favorable effects of EPO. There was an overall death rate of 16.4% (n=42 of 256) in the EPO and 9.0% (n=24 of 266) in the placebo group (OR, 1.98; 95% CI, 1.16 to 3.38;
P
=0.01) without any particular mechanism of death unexpected after stroke.

Conclusions—

Based on analysis of total intent-to-treat and per-protocol populations only, this is a negative trial that also raises safety concerns, particularly in patients receiving systemic thrombolysis.
Verification of the First 11 Years of IRI’s Seasonal Climate Forecasts
Authors: Barnston Anthony G. , Li Shuhua , Mason Simon J. , DeWitt David G. , Goddard Lisa , Gong Xiaofeng
Published: October 2009

This paper examines the quality of seasonal probabilistic forecasts of near-global temperature and precipitation issued by the International Research Institute for Climate and Society (IRI) from late 1997 through 2008, using mainly a two-tiered multimodel dynamical prediction system. Skill levels, while modest when globally averaged, depend markedly on season and location and average higher in the tropics than extratropics. To first order, seasons and regions of useful skill correspond to known direct effects as well as remote teleconnections from anomalies of tropical sea surface temperature in the Pacific Ocean (e.g., ENSO related) and in other tropical basins. This result is consistent with previous skill assessments by IRI and others and suggests skill levels beneficial to informed clients making climate risk management decisions for specific applications. Skill levels for temperature are generally higher, and less seasonally and regionally dependent, than those for precipitation, partly because of correct forecasts of enhanced probabilities for above-normal temperatures associated with warming trends. However, underforecasting of above-normal temperatures suggests that the dynamical forecast system could be improved through inclusion of time-varying greenhouse gas concentrations. Skills of the objective multimodel probability forecasts, used as the primary basis for the final forecaster-modified issued forecasts, are comparable to those of the final forecasts, but their probabilistic reliability is somewhat weaker. Automated recalibration of the multimodel output should permit improvements to their reliability, allowing them to be issued as is. IRI is currently developing single-tier prediction components.
Characterization of Precipitating Clouds by Ground-Based Measurements with the Triple-Frequency Polarized Microwave Radiometer ADMIRARI
Authors: Battaglia Alessandro , Saavedra Pablo , Rose Thomas , Simmer Clemens
Published: October 2009

A groundbreaking new-concept multiwavelength dual-polarized Advanced Microwave Radiometer for Rain Identification (ADMIRARI) has been built and continuously operated in two field campaigns: the Convective and Orographically Induced Precipitation Study (COPS) and the European Integrated Project on Aerosol Cloud Climate Air Quality Interactions (EUCAARI). The radiometer has 6 channels working in horizontal and vertical polarization at 10.65, 21.0, and 36.5 GHz, and it is completely steerable both in azimuth and in elevation. The instrument is suited to be operated in rainy conditions and is intended for retrieving simultaneously water vapor, rain, and cloud liquid water paths. To this goal the authors implemented a Bayesian retrieval scheme based on many state realizations simulated by the Goddard Cumulus Ensemble model that build up a prior probability density function of rainfall profiles. Detailed three-dimensional radiative transfer calculations, which account for the presence of nonspherical particles in preferential orientation, simulate the downwelling brightness temperatures and establish the similarity of radiative signatures and thus the probability that a given profile is actually observed. Particular attention is devoted to the sensitivity of the ADMIRARI signal to 3D effects, raindrop size distribution, and axial ratio parameterizations. The polarization and multifrequency signals represent key information to separate the effects introduced by non-Rayleigh scatterers and to separate rainwater (r-LWP) from the cloud water component (c-LWP). Long-term observations demonstrate that observed brightness temperatures and polarization differences can be well interpreted and reproduced by the simulated ones for all three channels simultaneously. Rough estimates of r-LWP derived from collocated observations with a micro rain radar confirm the rain/no rain separation and the variability trend of r-LWP provided by the radiometer-based retrieval algorithm. With this work the authors demonstrate the potential of ADMIRARI to retrieve information about the rain/cloud partitioning for midlatitude precipitation systems; future studies with this instrument will provide crucial information on rain efficiency of clouds for cloud modelers that might lead toward a better characterization of rain processes.
Cloud-Top Properties of Growing Cumulus prior to Convective Initiation as Measured by Meteosat Second Generation. Part I: Infrared Fields
Authors: Mecikalski John R. , MacKenzie Wayne M. , Koenig Marianne , Muller Sam
Published: October 2009

Infrared (IR) data from the Meteosat Second Generation (MSG) satellite are used to understand cloud-top signatures for growing cumulus clouds prior to known convective initiation (CI) events, or the first occurrence of a ≥35-dBZ echo from a new convective cloud. In the process, this study proposes how MSG IR fields may be used to infer three physical attributes of growing cumuli, cloud depth, cloud-top glaciation, and updraft strength, with limited information redundancy. These three aspects are observed as unique signatures within MSG IR data, for which this study seeks to relate to previous research, as well as develop a new understanding on which subset of IR information best identifies these attributes. Data from 123 subjectively identified CI events observed during the 2007 Convection and Orograpically Induced Precipitation Study (COPS) field experiment conducted over southern Germany and northeastern France are processed, per convective cell, to meet this study’s objectives. A total of 67 IR “interest fields” are initially assessed for growing cumulus clouds, with correlation and principal component analyses used to highlight the top 21 fields that are considered the best candidates for describing the three attributes. Using between 6 and 8 fields per category, a method is then proposed on how growing convective clouds may be quantified per 3-km2 pixel (or per cumulus cloud object) toward inferring each attribute. No independent CI-nowcasting analysis is performed, which instead is the subject of ongoing research.
Long-Term Changes in Rainfall over Eastern China and Large-Scale Atmospheric Circulation Associated with Recent Global Warming
Authors: Zhao Ping , Yang Song , Yu Rucong
Published: October 2009

Using precipitation data from rain gauge stations over China, the authors examine the long-term variation of the durations of persistent rainfall over eastern China for the past 40 years. The variation in the regional rainfall was related to a change in the global-mean surface temperature from the relatively cold period of the 1960s–70s to the relatively warm period of the 1980s–90s. Compared to the cold period, the persistent rainfall in the warm period began earlier and ended later over southern China, lengthening the rainy season by 23 days, but it began later and ended earlier over northern China, shortening the rainy season by 14 days. This change in the durations of persistent rainfall contributed to the pattern of the long-term change in rainfall: southern floods and northern droughts. The earlier beginning of the rainy season over southern China was associated with a more westward subtropical high over the western North Pacific and a stronger low-level low near the eastern Tibetan Plateau during spring. On the other hand, the later ending of the rainy season over southern China and the shorter rainy season over northern China were related to a more westward subtropical high over the western Pacific and a weaker trough near the eastern Tibetan Plateau during summer.

The snow cover over the Tibetan Plateau exhibited a positive trend in winter and spring, which increased the local soil moisture content and cooled the overlying atmosphere during spring and summer. The sea surface temperature over the tropical Indian Ocean and the western North Pacific also displayed a positive trend. The cooling over land and the warming over oceans reduced the thermal contrast between East Asia and the adjacent oceans. Moreover, the low-level low pressure system over East Asia weakened during summer. Under such circumstances, the East Asian summer monsoon circulation weakened, with anomalous northerly winds over eastern China. Correspondingly, the mei-yu front stagnated over the Yangtze River valley, and the associated pattern of vertical motions increased the rainfall over the valley and decreased the rainfall over northern China.
The Inverse Effect of Annual-Mean State and Annual-Cycle Changes on ENSO
Authors: An Soon-Il , Ham Yoo-Geun , Kug Jong-Seong , Timmermann Axel , Choi Jung , Kang In-Sik
Published: October 2009

The influence of the tropical Pacific annual-mean state on the annual-cycle amplitude and El Niño–Southern Oscillation (ENSO) variability is studied using the Max Planck Institute for Meteorology coupled general circulation model (CGCM) ECHAM5/Max Planck Institute Ocean Model (MPI-OM1). In a greenhouse warming experiment, an intensified annual cycle of sea surface temperature (SST) in the eastern tropical Pacific is associated with reduced ENSO variability, and vice versa.

Analysis showed that the annual-mean states, especially the surface warming in the western Pacific and the thermocline deepening in the central Pacific, which is concurrent with the strong annual cycle, act to suppress ENSO amplitude and to intensify the annual-cycle amplitude, and vice versa. The western Pacific warming acts to reduce air–sea coupling strength and to shorten the ocean adjustment time scale, and the deepening of central Pacific thermocline acts to diminish vertical advection of the anomalous ocean temperature by the annual-mean upwelling. Consequently, ENSO activity is suppressed by the annual-mean states during the strong annual-cycle decades, and the opposite case associated with the weak annual-cycle decades is also true. Furthermore, the time integration of an intermediate ENSO model forced with different background state configurations, and a stability analysis of its linearized version, show that annual-mean background states during the weak (strong) annual-cycle decades are characterized by an enhanced (reduced) linear growth rate of ENSO or similarly large (small) variability of ENSO. However, the annual-cycle component of the background state changes cannot significantly modify ENSO variability.

Using a hybrid coupled model, it is demonstrated that diagnosed annual-mean background states corresponding to a reduced (enhanced) annual cycle suppress (enhance) the development of the annual cycle of SST in the eastern equatorial Pacific, mainly through the weakening (intensifying) of zonal temperature advection of annual-mean SST by the annual-cycle zonal current. The above results support the idea that climate background state changes control both ENSO and the annual-cycle amplitude in opposing ways.
Structural Similarities and Differences in Climate Responses to CO2 Increase between Two Perturbed Physics Ensembles
Authors: Yokohata Tokuta , Webb Mark J. , Collins Matthew , Williams Keith D. , Yoshimori Masakazu , Hargreaves Julia C. , Annan James D.
Published: October 2009

The equilibrium climate sensitivity (ECS) of the two perturbed physics ensembles (PPE) generated using structurally different GCMs, Model for Interdisciplinary Research on Climate (MIROC3.2) and the Third Hadley Centre Atmospheric Model with slab ocean (HadSM3), is investigated. A method to quantify the shortwave (SW) cloud feedback by clouds with different cloud-top pressure is developed. It is found that the difference in the ensemble means of the ECS between the two ensembles is mainly caused by differences in the SW low-level cloud feedback. The ensemble mean SW cloud feedback and ECS of the MIROC3.2 ensemble is larger than that of the HadSM3 ensemble. This is likely related to the 1XCO2 low-level cloud albedo of the former being larger than that of the latter. It is also found that the largest contribution to the within-ensemble variation of ECS comes from the SW low-level cloud feedback in both ensembles. The mechanism that causes the within-ensemble variation is different between the two ensembles. In the HadSM3 ensemble, members with large 1XCO2 low-level cloud albedo have large SW cloud feedback and large ECS; ensemble members with large 1XCO2 cloud cover have large negative SW cloud feedback and relatively low ECS. In the MIROC3.2 ensemble, the 1XCO2 low-level cloud albedo is much more tightly constrained, and no relationship is found between it and the cloud feedback. These results indicate that both the parametric uncertainties sampled in PPEs and the structural uncertainties of GCMs are important and worth further investigation.
The Double-ITCZ Syndrome in Coupled General Circulation Models: The Role of Large-Scale Vertical Circulation Regimes
Authors: Bellucci A. , Gualdi S. , Navarra A.
Published: October 2009

The double–intertropical convergence zone (DI) systematic error, affecting state-of-the-art coupled general circulation models (CGCMs), is examined in the multimodel Intergovernmental Panel on Climate Change (IPCC) Fourth Assessment Report (AR4) ensemble of simulations of the twentieth-century climate. The aim of this study is to quantify the DI error on precipitation in the tropical Pacific, with a specific focus on the relationship between the DI error and the representation of large-scale vertical circulation regimes in climate models. The DI rainfall signal is analyzed using a regime-sorting approach for the vertical circulation regimes. Through the use of this compositing technique, precipitation events are regime sorted based on the large-scale vertical motions, as represented by the midtropospheric Lagrangian pressure tendency ω500 dynamical proxy. This methodology allows partition of the precipitation signal into deep and shallow convective components. Following the regime-sorting diagnosis, the total DI bias is split into an error affecting the magnitude of precipitation associated with individual convective events and an error affecting the frequency of occurrence of single convective regimes. It is shown that, despite the existing large intramodel differences, CGCMs can be ultimately grouped into a few homogenous clusters, each featuring a well-defined rainfall–vertical circulation relationship in the DI region. Three major behavioral clusters are identified within the AR4 models ensemble: two unimodal distributions, featuring maximum precipitation under subsidence and deep convection regimes, respectively, and one bimodal distribution, displaying both components. Extending this analysis to both coupled and uncoupled (atmosphere only) AR4 simulations reveals that the DI bias in CGCMs is mainly due to the overly frequent occurrence of deep convection regimes, whereas the error on rainfall magnitude associated with individual convective events is overall consistent with errors already present in the corresponding atmosphere stand-alone simulations. A critical parameter controlling the strength of the DI systematic error is identified in the model-dependent sea surface temperature (SST) threshold leading to the onset of deep convection (THR), combined with the average SST in the southeastern Pacific. The models featuring a THR that is systematically colder (warmer) than their mean surface temperature are more (less) prone to exhibit a spurious southern intertropical convergence zone.