bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of ICD-10 Diagnostic Guidelines and Research Criteria for Enduring Personality Change after Catastrophic Experience
Authors: Beltran Ruth O. , Silove Derrick , Llewellyn Gwynnyth M.
Published: February 2009

Enduring personality change after catastrophic experience (EPCACE) is a diagnostic category included in the International Statistical Classification of Diseases and Related Health Problems, 10th revision (ICD-10), as one of the adult personality disorders. Preliminary investigation suggests there is considerable endorsement in principle for this new category amongst experts in the field of intentional human trauma, yet many aspects of the diagnosis remain contentious. EPCACE is described in 2 sets of ICD-10 criteria: the Diagnostic Criteria for Research (DCR) and the Clinical Description and Diagnostic Guidelines (CDDG). Studies have found that the use of the DCR and CDDG for some disorders has created issues related to lack of compatibility and agreement between these 2 versions. This article examines the similarities and differences between the DCR and CDDG for EPCACE. Using background literature to inform our analysis, this article highlights issues related to the stressor criterion, symptom criteria, impairment criterion, criterion related to exclusion of personal vulnerability and early psychiatric history, symptom duration and relationship of post-traumatic-stress disorder with EPCACE. The similarities and differences between the research criteria and diagnostic guidelines of EPCACE are consistent with concerns already identified in the literature for other disorders. This presents a challenge to the way in which diagnostic criteria are conceptualized and stated.
Bullying Behavior Is Related to Suicide Attempts but Not to Self-Mutilation among Psychiatric Inpatient Adolescents
Authors: Luukkonen Anu-Helmi , Räsänen Pirkko , Hakko Helinä , Riala Kaisa
Published: February 2009

Background: To investigate the association of bullying behavior with suicide attempts and self-mutilation among adolescents. Sampling andMethods: The study sample consisted of 508 Finnish adolescents (age 12–17 years) admitted to psychiatric inpatient care between April 2001 and March 2006. DSM-IV psychiatric diagnoses and variables measuring suicidal behavior (i.e. suicide attempts and self-mutilation) and bullying behavior (i.e. a victim, a bully or a bully-victim) were obtained from the Schedule for Affective Disorder and Schizophrenia for School-Age Children Present and Lifetime (K-SADS-PL). Logistic regression analyses were conducted to examine the impact of being a victim, a bully or both a bully and a victim on suicide attempts and self-mutilation. Results: After adjusting for age, school factors, family factors and psychiatric disorders, there was a higher risk of suicide attempts in girls who were victims of bullying (OR = 2.07, CI = 1.04–4.11, p = 0.037) or who bullied others (OR = 3.27, CI = 1.08–9.95, p = 0.037). Corresponding associations were not found for boys; nor was any association of bullying behavior with self-mutilation found among either sex. Conclusions: Among girls, being bullied or bullying others are both potential risk factors for suicidal behavior. Psychiatric assessment and treatment should thus be considered not only for victims of bullying, but also for bullies. Suicide-prevention programs should also routinely include interventions to reduce bullying. However, the generalization of our findings to all adolescents is limited because our study sample consisted of psychiatric adolescent patients. In addition, some of the possible findings might have remained statistically insignificant due to the small sample size among adolescents who had performed suicide attempts or self-mutilation.
Interaction between Interleukin-8 and Methylenetetrahydrofolate Reductase Genes Modulates Alzheimer’s Disease Risk
Authors: Li Keshen , Liu Shengyuan , Yao Songpo , Wang Binyou , Dai Dawei , Yao Lifen
Published: February 2009

Background/Aim: Interleukin-8 (IL-8), a potent chemoattractant for neutrophils, has been implicated in the pathogenesis of Alzheimer’s disease (AD). The ability of individuals to produce high levels of IL-8 is partially determined by the IL-8 –251 T/A polymorphism. Therefore, we investigated the association between this polymorphism and AD in a Chinese population. Additionally, in light of the stimulatory effect of homocysteine on the production of IL-8, we also sought to determine whether the methylenetetrahydrofolate reductase (MTHFR) gene 677 C/T variant, a genetic modifier of the serum homocysteine level, may interact with the IL-8 –251 polymorphism in determining the AD risk. Methods: Genotyping of 198 AD patients and 240 matched controls was performed by PCR-RFLP. Results: The presence of the MTHFR 677 C/T and 677 T/T genotypes conferred a marginally significant increase in the risk for AD (OR = 1.666, 95% CI = 1.022–2.715, and OR = 1.892, 95% CI = 1.124–3.187) and the presence of the IL-8 –251 polymorphism was not associated with AD. However, the OR for AD associated with joint occurrence of the MTHFR 677 T/T and the IL-8 –251 A/A genotypes was 2.512 (95% CI = 1.151–5.483). Conclusion: Our data suggest a critical role for IL-8/MTHFR interactions in the development of AD.
Associations of Vitamin D Receptor, Calcium-Sensing Receptor and Parathyroid Hormone Gene Polymorphisms with Calcium Homeostasis and Peripheral Bone Density in Adult Finns
Authors: Laaksonen M.M.L. , Outila T.A. , Kärkkäinen M.U.M. , Kemi V.E. , Rita H.J. , Perola M. , Valsta L.M. , Lamberg-Allardt C.J.E.
Published: February 2009

Background: Thus far the search for osteoporosis candidate genes has focused less attention on the regulation of calcium homeostasis. Associations of vitamin D receptor (VDR) FokI, calcium-sensing receptor (CaSR) A986S and parathyroid hormone (PTH) BstBI polymorphisms with calcium homeostasis and peripheral bone density were investigated in adult Finns. Methods: The subgroup of the population-based FINRISK survey consists of 339 healthy adults aged 31–43 years. Lifestyle data were assessed with questionnaires and food diaries. DNA was isolated from blood, and biochemical determinants of calcium metabolism were measured from blood and 24-hour urine samples. Bone mineral density (BMD) was measured using the DXA method at the distal forearm and by quantitative ultrasound (broadband ultrasound attenuation and speed of sound) at the calcaneus. Subjects were genotyped for VDR FokI, CaSR A986S and PTH BstBI polymorphisms. Results: The CaSR 986S allele was associated with higher serum ionized calcium (p = 0.014). Forearm BMD was lowest for the PTH BstBI genotype bb in males (p = 0.023). VDR FokI and PTH BstBI polymorphisms showed a significant interaction on serum PTH (p = 0.010). The other gene–gene or diet–gene interactions studied showed no significant results. Conclusions: VDR, CaSR and PTH contribute to the genetic regulation of calcium homeostasis and peripheral bone density.
Brain-Derived Neurotrophic Factor mRNA Expression in the Brain of the Teleost Fish, Anguilla anguilla, the European Eel
Authors: Dalton Victoria S. , Borich Suzanne M. , Murphy Paula , Roberts Barry L.
Published: February 2009

The spatial expression pattern of Brain-Derived Neurotrophic Factor (BDNF) mRNA in the brain of the European eel (Anguilla anguilla) was determined using non-radioactive in situ hybridization, and mapped and compared to that of other vertebrates. Riboprobes were prepared based on a partial cDNA coding sequence for A. anguilla BDNF that was amplified using degenerate primers, cloned and sequenced. As in other animal groups, in the eel, BDNF mRNA expression was seen in the telencephalon, hypothalamus, tectum, many primary and secondary sensory centers, and cranial motor nuclei. However, in contrast to mammals, BDNF mRNA expression was observed in some brain stem nuclei, such as the reticular formation, that contain cell bodies of neurons that project down the spinal cord. We suggest that these differences might relate to the continual growth of teleost fish.
A Nutrigenomic Inflammation-Related PBMC-Based Approach to Predict the Weight-Loss Regain in Obese Subjects
Authors: Goyenechea Estibaliz , Parra Dolores , Crujeiras Ana B. , Abete Itziar , Martínez J. Alfredo
Published: February 2009

Background: Long-term maintenance of a dietary-induced weight loss continues to be a major health problem and warrants research on innovative approaches to understand weight stability. We investigated the role of the proinflammatory status on weight changes in obese subjects receiving a low-calorie diet (LCD) and during the subsequent 6-month weight maintenance period. Methods: Eighty-four subjects (age: 34.2 ± 0.53 years; body mass index, BMI: 30.4 ± 1.8 kg/m2) followed an 8-week LCD intervention and were contacted again 6 months later. Body composition, circulating proinflammatory markers [tumor necrosis factor (TNF)α, interleukin-6, C-reactive protein and leptin] and mRNA levels of inflammation-related genes [TNFα and nuclear factor (NF) κBtranscription subunits] in peripheral blood mononuclear cells (PBMC) were evaluated. Results: The 6-month weight regain was predicted by high concentrations of TNFα at LCD completion (OR = 4.21, p = 0.036) along with the baseline amount of fat mass (OR = 7.23, p = 0.029). In addition, baseline leptin concentrations (p = 0.028) as well as mRNA levels of TNFα and NFκB subunits were higher at the end of the dietary intervention (p < 0.05) in PBMC of subjects who regained ≥10% of the dietary-induced weight loss. Conclusions: These findings demonstrate a role for the proinflammatory state and body adiposity in the prediction of weight-loss regain. This relationship could contribute to the design of more personalized nutritional treatments in obese patients and favor the weight maintenance process.
Changes in the PQRST Intervals and Heart Rate Variability Associated with Rewarming in Two Newborns Undergoing Hypothermia Therapy
Authors: Lasky Robert E. , Parikh Nehal A. , Williams Amber L. , Padhye Nikhil S. , Shankaran Seetha
Published: February 2009

Background: Little is known about the effects of hypothermia therapy and subsequent rewarming on the PQRST intervals and heart rate variability (HRV) in term newborns with hypoxic-ischemic encephalopathy (HIE). Objectives: This study describes the changes in the PQRST intervals and HRV during rewarming to normal core body temperature of 2 newborns with HIE after hypothermia therapy. Methods: Within 6 h after birth, 2 newborns with HIE were cooled to a core body temperature of 33.5°C for 72 h using a cooling blanket, followed by gradual rewarming (0.5°C per hour) until the body temperature reached 36.5°C. Custom instrumentation recorded the electrocardiogram from the leads used for clinical monitoring of vital signs. Generalized linear mixed models were calculated to estimate temperature-related changes in PQRST intervals and HRV. Results: For every 1°C increase in body temperature, the heart rate increased by 9.2 bpm (95% CI 6.8–11.6), the QTc interval decreased by 21.6 ms (95% CI 17.3–25.9), and low and high frequency HRV decreased by 0.480 dB (95% CI 0.052–0.907) and 0.938 dB (95% CI 0.460–1.416), respectively. Conclusions: Hypothermia-induced changes in the electrocardiogram should be monitored carefully in future studies.
Comparison of Survival in Advanced Non-Small Cell Lung Cancer Patients in the Pre- and Post-Gefitinib Eras
Authors: Kim Hyo Song , Park Keunchil , Jun Hyun Jung , Yi Seong Yoon , Lee Jeeyun , Ahn Jin Seok , Park Yeon Hee , Kim Seonwoo , Lee Sangcheol , Ahn Myung-Ju
Published: February 2009

Background: The aim of this study was to analyze the survival difference between advanced non-small cell lung cancer (NSCLC) patients in the pre-gefitinib and post-gefitinib eras in Korea. Patients and Methods: 830 patients with advanced/metastatic or recurrent NSCLC who received palliative chemotherapy were retrospectively reviewed. Using a matched-pair case-control study design, 334 pairs from the pre-gefitinib era (January 1999 to December 2001) and the post-gefitinib era (January 2002 to December 2005) were matched by age, sex and histology. Results: The median overall survival from the date of first administration of palliative chemotherapy was significantly longer in the post-gefitinib era (11.5 vs. 19.3 months, p< 0.001). Multivariate analysis showed that gefitinib was associated with longer overall survival (hazard ratio 0.58, p< 0.001) as were never having been a smoker, adenocarcinoma histology, good performance, stage IIIB, ≥3 prior episodes of chemotherapy, platinum-based chemotherapy and previous docetaxel or pemetrexed treatment. Patients in the post-gefitinib era showed significantly longer overall survival in almost all subgroups. Gefitinib treatment was of significantly greater benefit in patients with adenocarcinoma than in those with non-adenocarcinoma (test for interaction p< 0.001). Conclusion: These results indicate a significant improvement of survival in advanced NSCLC patients treated with gefitinib in Korea.
Comparison of Gastric Emptying and Plasma Ghrelin Levels in Patients with Functional Dyspepsia and Non-Erosive Reflux Disease
Authors: Shindo Tomotaka , Futagami Seiji , Hiratsuka Tetsuro , Horie Akane , Hamamoto Tatsuhiko , Ueki Nobue , Kusunoki Masafumi , Miyake Kazumasa , Gudis Katya , Tsukui Taku , Iwakiri Katsuhiko , Sakamoto Choitsu
Published: February 2009

Background and Aims: The symptoms of postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS), the two subtypes of functional dyspepsia (FD) under the new Rome III classification, tend to overlap with those of non-erosive reflux disease (NERD). Plasma ghrelin levels have been associated with gastric motility; however, clinical studies have yet to examine this relationship among patients with PDS, EPS or NERD. Thus, this study aims to evaluate the correlation between gastric emptying and ghrelin levels as possible candidate factors for gastric motility in these diseases. Methods: One hundred and fifty-one patients presenting with typical symptoms of FD (EPS, n = 36; PDS, n = 76) or NERD (n = 39), and 20 healthy volunteers were enrolled. Gastric motility was evaluated with the Tmax value as a marker of gastric emptying using the 13C-acetate breath test. We used Rome III criteria to evaluate upper abdominal symptoms, and SRQ-D scores to determine depression status. We measured both acylated and des-acylated ghrelin levels by ELISA methods. Results: The Tmax value in PDS patients was significantly higher than in healthy volunteers. Acylated ghrelin levels were significantly lower in NERD and PDS patients than in healthy volunteers. Interestingly, there was significant correlation between the acylated ghrelin levels and Tmax value in PDS patients but not in EPS or NERD patients. Conclusion: Our results suggest that acylated ghrelin might play an important role in the pathophysiology of PDS patients through its effect on gastric emptying.
Clinical and Organizational Content of Clinical Pathways for Digestive Surgery: A Systematic Review
Authors: Lemmens L. , van Zelm R. , Borel Rinkes I. , van Hillegersberg R. , Kerkkamp H.
Published: February 2009

Background/Aims: Oncology surgery of the gastrointestinal tract is complex and infamous for its high complication rates. One of the methods for implementing interventions to optimize the patients’ condition and to enhance postoperative outcome is the development and implementation of a clinical pathway. The aim of this study was to analyze the content, i.e. the interventions of clinical pathways for digestive surgery and their effects on postoperative outcome measures. Methods: We performed a systematic review to study clinical pathways in hospital care for adult patients undergoing elective surgery of the stomach, esophagus, pancreas, liver, colon or rectum. The MEDLINE, EMBASE and CINAHL literature databases were searched. Results: The most common interventions in the clinical pathways in this review were defined in the pre- and postoperative phase and included: nutritional management, pain management, mobilization, education and discharge planning. The primary aim of these interventions was to enhance postoperative recovery. Conclusion: Clinical pathways for digestive surgery contain specific interventions to improve postoperative outcome. Most of these interventions are in accordance with the Enhanced Recovery After Surgery (ERAS) protocol, which is an evidence-based protocol for care after colon resections. They result in reduced length of stay without compromising other postoperative outcome measures.
Activation of the Bone Morphogenetic Protein Receptor by H11Kinase/Hsp22 Promotes Cardiac Cell Growth and Survival
Authors: Sui Xiangzhen , Li Dan , Qiu Hongyu , Gaussin Vinciane , Depre Christophe
Published: February 2009

H11 kinase/Hsp22 (H11K) is a chaperone promoting cardiac cell growth and survival through the activation of Akt, a downstream effector of phosphatidylinositol 3-kinase (PI3K). In this study, we tested whether H11K-induced activation of the PI3K/Akt pathway is mediated by the bone morphogenetic protein (BMP) signaling, both in a transgenic mouse model with cardiac-specific overexpression of H11K and in isolated cardiac myocytes. Microarrays in hearts from transgenic compared to wild-type mice showed an upregulation of the BMP receptors Alk3 and BMPR-II, and of their ligand BMP4 (
P
<0.01 versus wild type). Activation of the BMP pathway in transgenic mice was confirmed by increased phosphorylation of the “canonical” BMP effectors Smad 1/5/8 (
P
<0.01 versus wild type). In isolated myocytes, adenovirus-mediated overexpression of H11K was accompanied by a significant (
P
<0.01) increase in PI3K activity, phospho-Akt, Smad 1/5/8 phosphorylation and [
3
H]phenylalanine incorporation, and by a 70% reduction in H
2
O
2
-mediated apoptosis. All these effects were abolished by the BMP antagonist noggin. In presence of BMP4, Smad 1/5/8 phosphorylation was enhanced by 5-fold on H11K overexpression but decreased by 3-fold on H11K knockdown (
P
<0.01 versus control), showing that H11K potentiates the BMP signaling. In pull-down experiments, H11K increased both the association of Alk3 and BMPR-II together, and their interaction with the transforming growth factor-β–activated kinase (TAK)1, a “noncanonical” mediator of the BMP receptor signaling. TAK1 inhibition prevented H11K-mediated activation of Akt. Therefore, potentiation of the BMP receptor by H11K promotes an activation of the PI3K/Akt pathway mediated by TAK1, which dictates the physiological effects of H11K on cardiac cell growth and survival.
Osteopontin
Authors: Szalay Gudrun , Sauter Martina , Haberland Michael , Zuegel Ulrich , Steinmeyer Andreas , Kandolf Reinhard , Klingel Karin
Published: February 2009

The characteristics of dilated cardiomyopathy (DCM) resulting from chronic viral myocarditis are remodeling processes of the extracellular matrix. Based on our findings of enhanced osteopontin (OPN) expression in inflamed human hearts, we further investigated in the murine model of acute and chronic coxsackievirus (CV)B3-myocarditis the role of OPN regarding its involvement in resolution of cardiac virus infection and fibrosis. In hearts of A.BY/SnJ mice susceptible to chronic CVB3-myocarditis, a pronounced increase of OPN expression levels was detected by microarray analysis and quantitative RT-PCR during acute stages of myocarditis. Combined immunohistochemistry and in situ hybridization identified infiltrating macrophages as main OPN producers. In contrast to resistant C57BL/6 and OPN gene-deficient mice, transcription levels of matrix metalloproteinase-3, TIMP1 (tissue inhibitor of metalloproteinases-1), uPA (urokinase-type plasminogen activator), and transforming growth factor β1 were elevated in susceptible mice, and as a consequence, procollagen-1α mRNA expression and fibrosis was considerably enhanced. Treatment of infected susceptible mice with the vitamin D analog ZK 191784 led to decreased myocardial expression levels of OPN, metalloproteinase-3, TIMP1, uPA, and procollagen-1α and subsequently to reduced fibrosis. Concurrently, the fibrosis-relevant signaling molecules pERK (phosphorylated extracellular signal-regulated kinase) and pAkt (phosphorylated Akt), increased in A.BY/SnJ mice, were diminished in ZK 191784–treated mice. Here, we show that high expression levels of OPN in acute myocarditis are associated with consecutive development of extensive fibrosis that can be reduced by treatment with a vitamin D analog. Thus, OPN may serve as a diagnostic tool as well as a potential therapeutic target to limit cardiac remodeling in chronic myocarditis.
Cardiac Myosin Binding Protein-C Phosphorylation in a β-Myosin Heavy Chain Background
Authors: Sadayappan Sakthivel , Gulick James , Klevitsky Raisa , Lorenz John N. , Sargent Michelle , Molkentin Jeffery D. , Robbins Jeffrey
Published: February 2009

Background—

Cardiac myosin binding protein-C (cMyBP-C) phosphorylation modulates cardiac contractility. When expressed in cMyBP-C–null (cMyBP-C
(t/t)
) hearts, a cMyBP-C phosphomimetic (cMyBP-C
AllP+
) rescued cardiac dysfunction and protected the hearts from ischemia/reperfusion injury. However, cMyBP-C function may be dependent on the myosin isoform type. Because these replacements were performed in the mouse heart, which contains predominantly α-myosin heavy chain (α-MyHC), the applicability of the data to humans, whose cardiomyocytes contain predominantly β-MyHC, is unclear. We determined the effect(s) of cMyBP-C phosphorylation in a β-MyHC transgenic mouse heart in which >80% of the α-MyHC was replaced by β-MyHC, which is the predominant myosin isoform in human cardiac muscle.

Methods and Results—

To determine the effects of cMyBP-C phosphorylation in a β-MyHC background, transgenic mice expressing normal cMyBP-C (cMyBP-C
WT
), nonphosphorylatable cMyBP-C (cMyBP-C
AllP
−
), or cMyBP-C
AllP+
were bred into the β-MyHC background (β). These mice were then crossed into the cMyBP-C
(t/t)
background to ensure the absence of endogenous cMyBP-C. cMyBP-C
(t/t)/β
and cMyBP-C
AllP
−
:(t/t)/β
mice died prematurely because of heart failure, confirming that cMyBP-C phosphorylation is essential in the β-MyHC background. cMyBP-C
AllP+:(t/t)/β
and cMyBP-C
WT:(t/t)/β
hearts showed no morbidity and mortality, and cMyBP-C
AllP+:(t/t)/β
hearts were significantly cardioprotected from ischemia/reperfusion injury.

Conclusions—

cMyBP-C phosphorylation is necessary for basal myocardial function in the β-MyHC background and can preserve function after ischemia/reperfusion injury. Our studies justify exploration of cMyBP-C phosphorylation as a therapeutic target in the human heart.
Reciprocal Regulation of Myocardial microRNAs and Messenger RNA in Human Cardiomyopathy and Reversal of the microRNA Signature by Biomechanical Support
Authors: Matkovich Scot J. , Van Booven Derek J. , Youker Keith A. , Torre-Amione Guillermo , Diwan Abhinav , Eschenbacher William H. , Dorn Lisa E. , Watson Mark A. , Margulies Kenneth B. , Dorn Gerald W.
Published: February 2009

Background—

Much has been learned about transcriptional control of cardiac gene expression in clinical and experimental congestive heart failure (CHF), but less is known about dynamic regulation of microRNAs (miRs) in CHF and during CHF treatment. We performed comprehensive microarray profiling of miRs and messenger RNAs (mRNAs) in myocardial specimens from human CHF with (n=10) or without (n=17) biomechanical support from left ventricular assist devices in comparison to nonfailing hearts (n=11).

Methods and Results—

Twenty-eight miRs were upregulated >2.0-fold (
P
<0.001) in CHF, with nearly complete normalization of the heart failure miR signature by left ventricular assist device treatment. In contrast, of 444 mRNAs that were altered by >1.3-fold in failing hearts, only 29 mRNAs normalized by as much as 25% in post–left ventricular assist device hearts. Unsupervised hierarchical clustering of upregulated miRs and mRNAs with nearest centroid analysis and leave-1-out cross-validation revealed that combining the miR and mRNA signatures increased the ability of RNA profiling to serve as a clinical biomarker of diagnostic group and functional class.

Conclusions—

These results show that miRs are more sensitive than mRNAs to the acute functional status of end-stage heart failure, consistent with important functions for regulated miRs in the myocardial response to stress. Combined miR and mRNA profiling may have superior potential as a diagnostic and prognostic test in end-stage cardiomyopathy.
Prevention of Rheumatic Fever and Diagnosis and Treatment of Acute Streptococcal Pharyngitis
Authors: Gerber Michael A. , Baltimore Robert S. , Eaton Charles B. , Gewitz Michael , Rowley Anne H. , Shulman Stanford T. , Taubert Kathryn A.
Published: February 2009

Primary prevention of acute rheumatic fever is accomplished by proper identification and adequate antibiotic treatment of group A β-hemolytic streptococcal (GAS) tonsillopharyngitis. Diagnosis of GAS pharyngitis is best accomplished by combining clinical judgment with diagnostic test results, the criterion standard of which is the throat culture. Penicillin (either oral penicillin V or injectable benzathine penicillin) is the treatment of choice, because it is cost-effective, has a narrow spectrum of activity, and has long-standing proven efficacy, and GAS resistant to penicillin have not been documented. For penicillin-allergic individuals, acceptable alternatives include a narrow-spectrum oral cephalosporin, oral clindamycin, or various oral macrolides or azalides. The individual who has had an attack of rheumatic fever is at very high risk of developing recurrences after subsequent GAS pharyngitis and needs continuous antimicrobial prophylaxis to prevent such recurrences (secondary prevention). The recommended duration of prophylaxis depends on the number of previous attacks, the time elapsed since the last attack, the risk of exposure to GAS infections, the age of the patient, and the presence or absence of cardiac involvement. Penicillin is again the agent of choice for secondary prophylaxis, but sulfadiazine or a macrolide or azalide are acceptable alternatives in penicillin-allergic individuals. This report updates the 1995 statement by the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee. It includes new recommendations for the diagnosis and treatment of GAS pharyngitis, as well as for the secondary prevention of rheumatic fever, and classifies the strength of the recommendations and level of evidence supporting them.
Reporting Standards for Endovascular Repair of Saccular Intracranial Cerebral Aneurysms
Authors: Meyers Philip M. , Schumacher H. Christian , Higashida Randall T. , Derdeyn Colin P. , Nesbit Gary M. , Sacks David , Wechsler Lawrence R. , Bederson Joshua B. , Lavine Sean D. , Rasmussen Peter
Published: February 2009

Background and Purpose—

The goal of this article is to provide consensus recommendations for reporting standards, terminology, and written definitions when reporting on the radiological evaluation and endovascular treatment of intracranial, cerebral aneurysms. These criteria can be used to design clinical trials, to provide uniformity of definitions for appropriate selection and stratification of patients, and to allow analysis and meta-analysis of reported data.

Methods—

This article was written under the auspices of the Joint Writing Group of the Technology Assessment Committee, Society of NeuroInterventional Surgery, Society of Interventional Radiology; Joint Section on Cerebrovascular Neurosurgery of the American Association of Neurological Surgeons and Congress of Neurological Surgeons; and Section of Stroke and Interventional Neurology of the American Academy of Neurology. A computerized search of the National Library of Medicine database of literature (PubMed) from January 1991 to December 2007 was conducted with the goal to identify published endovascular cerebrovascular interventional data about the assessment and endovascular treatment of cerebral aneurysms useful as benchmarks for quality assessment. We sought to identify those risk adjustment variables that affect the likelihood of success and complications. This article offers the rationale for different clinical and technical considerations that may be important during the design of clinical trials for endovascular treatment of cerebral aneurysms. Included in this guidance article are suggestions for uniform reporting standards for such trials. These definitions and standards are primarily intended for research purposes; however, they should also be helpful in clinical practice and applicable to all publications.

Conclusions—

The evaluation and treatment of brain aneurysms often involve multiple medical specialties. Recent reviews by the American Heart Association have surveyed the medical literature to develop guidelines for the clinical management of ruptured and unruptured cerebral aneurysms. Despite efforts to synthesize existing knowledge on cerebral aneurysm evaluation and treatment, significant inconsistencies remain in nomenclature and definition for research and reporting purposes. These operational definitions were selected by consensus of a multidisciplinary writing group to provide consistency for reporting on imaging in clinical trials and observational studies involving cerebral aneurysms. These definitions should help different groups to publish results that are directly comparable.
Reporting Standards for Angioplasty and Stent-Assisted Angioplasty for Intracranial Atherosclerosis
Authors: Schumacher H. Christian , Meyers Philip M. , Higashida Randall T. , Derdeyn Colin P. , Lavine Sean D. , Nesbit Gary M. , Sacks David , Rasmussen Peter , Wechsler Lawrence R.
Published: February 2009

Background and Purpose—

Intracranial cerebral atherosclerosis causes ischemic stroke in a significant number of patients. Technological advances over the past 10 years have enabled endovascular treatment of intracranial atherosclerotic stenosis. The number of patients treated with angioplasty or stent-assisted angioplasty for this condition is increasing. Given the lack of universally accepted definitions, the goal of this document is to provide consensus recommendations for reporting standards, terminology, and written definitions when reporting clinical and radiological evaluation, technique, and outcome of endovascular treatment using angioplasty or stent-assisted angioplasty for stenotic and occlusive intracranial atherosclerosis.

Summary of Report—

This article was written under the auspices of Joint Writing Group of the Technology Assessment Committee, Society of NeuroInterventional Surgery, Society of Interventional Radiology; Joint Section on Cerebrovascular Neurosurgery of the American Association of Neurological Surgeons and Congress of Neurological Surgeons; and the Section of Stroke and Interventional Neurology of the American Academy of Neurology. A computerized search of the National Library of Medicine database of literature (PubMed) from January 1997 to December 2007 was conducted with the goal to identify published endovascular cerebrovascular interventional data in stenotic intracranial atherosclerosis that could be used as benchmarks for quality assessment. We sought to identify those risk adjustment variables that affect the likelihood of success and complications. This document offers the rationale for different clinical and technical considerations that may be important during the design of clinical trials for endovascular treatment of intracranial stenotic and occlusive atherosclerosis. Included in this guidance document are suggestions for uniform reporting standards for such trials. These definitions and standards are primarily intended for research purposes; however, they should also be helpful in clinical practice and applicable to all publications.

Conclusion—

In summary, the definitions proposed represent recommendations for constructing useful research data sets. The intent is to facilitate production of scientifically rigorous results capable of reliable comparisons between and among similar studies. In some cases, the definitions contained here are recommended by consensus of a panel of experts in this writing group for consistency in reporting and publication. These definitions should allow different groups to publish results that are directly comparable.
Analysis of 1008 Consecutive Patients Aged 15 to 49 With First-Ever Ischemic Stroke
Authors: Putaala Jukka , Metso Antti J. , Metso Tiina M. , Konkola Nina , Kraemer Yvonn , Haapaniemi Elena , Kaste Markku , Tatlisumak Turgut
Published: February 2009

Background and Purpose—

To analyze trends in occurrence, risk factors, etiology, and neuroimaging features of ischemic stroke in young adults in a large cohort.

Methods—

We evaluated all 1008 consecutive ischemic stroke patients aged 15 to 49 admitted to Helsinki University Central Hospital, 1994 to 2007. Etiology was classified by Trial of Org 10172 in Acute Stroke Treatment criteria. Comparisons were done between groups stratified by gender and age.

Results—

Estimated annual occurrence was 10.8/100 000 (range 8.4 to 13.0), increasing exponentially with aging. Of our 628 male and 380 female (ratio 1.7:1) patients, females were preponderant among those <30, whereas male dominance rapidly increased around age of 44. The most frequent risk factors were dyslipidemia (60%), smoking (44%), and hypertension (39%). Males and patients >44 clearly had more risk factors. Cardioembolism (20%) and cervicocerebral artery dissection (15%) were the most frequent etiologic subgroups. Proportions of large-artery atherosclerosis (8%) and small-vessel disease (14%) began to enlarge at age 35, whereas frequency of undetermined etiology (33%) decreased along aging. Posterior circulation infarcts were more common among patients <45 years of age. Left hemisphere infarcts were more frequent in general. There were 235 (23%) patients with multiple and 126 (13%) with silent infarcts, and 55 (5%) patients had leukoaraiosis.

Conclusions—

The frequency of ischemic stroke increases sharply at age 40. Etiology and risk factors start resembling those seen in the elderly in early midlife but causes defined in younger patients still are frequent in those aged 45 to 49. Subclinical infarcts were surprisingly common in the young.
Excessive Daytime Sleepiness Is an Independent Risk Indicator for Cardiovascular Mortality in Community-Dwelling Elderly
Authors: Empana Jean-Philippe , Dauvilliers Yves , Dartigues Jean-François , Ritchie Karen , Gariepy Jerome , Jouven Xavier , Tzourio Christophe , Amouyel Philippe , Besset Alain , Ducimetiere Pierre
Published: February 2009

Background and Purpose—

Excessive daytime sleepiness, one of the most frequent sleep complaints in the elderly, may affect survival, but inconsistent results have been observed in that population so far. We therefore estimated the risk of mortality for excessive daytime sleepiness (EDS) in community-dwelling elderly participating in the Three City Study.

Methods—

The Three City Study is a French population-based multicenter prospective study including 9294 subjects (60% women) aged ≥65 years at recruitment between 1999 to 2001. At baseline, 8269 subjects rated EDS and nocturnal sleep complaints as never, rare, regular, and frequent in response to an administered questionnaire and provided information on medication use for sleep or anxiety. Hazard ratios (HR) of EDS (regular or frequent) for mortality over 6 years were estimated by a Cox proportional hazard model.

Results—

At baseline, 18.7% of the study participants had regular or frequent EDS. After 6 years of follow-up, 762 subjects had died including 260 from cancer and 196 from cardiovascular disease. EDS was associated with a significant 33% increased risk of mortality (95% CI: 1.13 to 1.61) after adjustment for age, gender, study center, body mass index, previous cardiovascular disease, Mini Mental State Examination score, and cardiovascular risk factors. Further adjustment for current use of medication for sleep and for depressive symptoms slightly diminished the HRs. EDS was equally predictive of mortality in those who snored loudly and in those who did not. EDS was related to cardiovascular mortality but not to mortality attributable to cancer.

Conclusion—

EDS might be independently associated with total and cardiovascular mortality in community-dwelling elderly.
Prevalence of Asymptomatic Carotid Artery Stenosis According to Age and Sex
Authors: de Weerd Marjolein , Greving Jacoba P. , de Jong Anne W.F. , Buskens Erik , Bots Michiel L.
Published: February 2009

Background and Purpose—

In the discussion on the value of population-wide screening for asymptomatic carotid artery stenosis (ACAS), reliable prevalence estimates are crucial. We set out to provide reliable age- and sex-specific prevalence estimates of ACAS through a systematic literature review and meta-regression analysis.

Methods—

We searched PubMed and EmBase until December 2007 for studies that reported the prevalence of ACAS in a population free of symptomatic carotid artery disease. Data were extracted with use of a standardized form on participants’ characteristics, assessment method, study quality, and prevalence estimates for moderate (≥50% stenosis) and severe (≥70% stenosis) ACAS. Metaregression was used to investigate sources of heterogeneity.

Results—

Forty studies fulfilled the inclusion criteria. There was considerable variation among studies with respect to demographics, methods of grading stenosis, and stenosis cutoff point used. The pooled prevalence of moderate stenosis was 4.2% (95% CI, 3.1% to 5.7%). Prevalence of moderate stenosis among people age <70 years was 4.8% (95% CI, 3.1% to 7.3%) in men and 2.2% (95% CI, 0.9% to 4.9%) in women. Among those ≥70 years, prevalence increased to 12.5% (95% CI, 7.4% to 20.3%) in men and to 6.9% (95% CI, 4.0% to 11.5%) in women. Metaregression showed that both age and sex significantly affected the prevalence of moderate stenosis. No contribution of study size, publication year, geographic region, assessment method, and study quality was found. The pooled prevalence of severe stenosis was 1.7% (95% CI, 0.7% to 3.9%).

Conclusions—

Prevalence of moderate stenosis increases with age in both men and women, but men at all ages have the higher prevalence estimates. The number of studies that allowed meaningful data synthesis of severe stenosis was limited.
Altered Fibrin Clot Structure/Function in Patients With Cryptogenic Ischemic Stroke
Authors: Undas Anetta , Podolec Piotr , Zawilska Krystyna , Pieculewicz Monika , Jedliński Ireneusz , Stępień Ewa , Konarska-Kuszewska Ewa , Węglarz Przemysław , Duszyńska Małgorzata , Hanschke Ewelina , Przewłocki Tadeusz , Tracz Wiesława
Published: February 2009

Background and Purpose—

We tested the hypothesis that fibrin structure/function is unfavorably altered in patients with cryptogenic ischemic stroke.

Methods—

Ex vivo plasma fibrin clot permeability, turbidimetry, and efficiency of fibrinolysis were determined in 89 patients with patent foramen ovale (PFO) and a history of first-ever stroke, 58 patients with first-ever stroke and no PFO, and 120 healthy controls.

Results—

Stroke patients, evaluated 3 to 19 months after the event, and controls did not differ with regard to age, sex, smoking, and fibrinogen. Stroke patients with or without PFO had lower clot permeability (
P
<0.0001), faster fibrin polymerization (
P
<0.0001), prolonged clot lysis time (
P
<0.0001), higher maximum D-dimer levels released from clots (
P
<0.0001), and maximum rate of D-dimer release (
P
=0.02) than controls. Time from stroke occurrence showed no association with any clot variables. Scanning electron microscopy of fibrin clots showed increased fiber diameter and density in stroke patients. Clots from stroke patients with PFO were more permeable and showed shorter lysis time compared to those without PFO, and this was related to lower proportion of smokers in the former group.

Conclusions—

Altered fibrin clot structure and resistance to fibrinolysis are associated with cryptogenic stroke.
Induced Normothermia Attenuates Cerebral Metabolic Distress in Patients With Aneurysmal Subarachnoid Hemorrhage and Refractory Fever
Authors: Oddo Mauro , Frangos Suzanne , Milby Andrew , Chen Isaac , Maloney-Wilensky Eileen , Murtrie Eileen Mac , Stiefel Michael , Kofke W. Andrew , Le Roux Peter D. , Levine Joshua M.
Published: February 2009

Background and Purpose—

The purpose of this study was to analyze whether fever control attenuates cerebral metabolic distress after aneurysmal subarachnoid hemorrhage (SAH).

Methods—

Eighteen SAH patients, who underwent intracranial pressure (ICP) and cerebral microdialysis monitoring and were treated with induced normothermia for refractory fever (body temperature ≥38.3°C, despite antipyretics), were studied. Levels of microdialysate lactate/pyruvate ratio (LPR) and episodes of cerebral metabolic crisis (LPR >40) were analyzed during fever and induced normothermia, at normal and high ICP (>20 mm Hg).

Results—

Compared to fever, induced normothermia resulted in lower LPR (40±24 versus 32±9,
P
<0.01) and a reduced incidence of cerebral metabolic crisis (13% versus 5%,
P
<0.05) at normal ICP. During episodes of high ICP, induced normothermia was associated with a similar reduction of LPR, fewer episodes of cerebral metabolic crisis (37% versus 8%,
P
<0.01), and lower ICP (32±11 versus 28±12 mm Hg,
P
<0.05).

Conclusions—

Fever control is associated with reduced cerebral metabolic distress in patients with SAH, irrespective of ICP.
SK
Ca
and IK
Ca
Channels, Myogenic Tone, and Vasodilator Responses in Middle Cerebral Arteries and Parenchymal Arterioles
Authors: Cipolla Marilyn J. , Smith Jeremiah , Kohlmeyer Meghan M. , Godfrey Julie A.
Published: February 2009

Background and Purpose—

The role of SK
Ca
and IK
Ca
channels in myogenic tone and endothelium-derived hyperpolarizing factor (EDHF) responsiveness was investigated under control conditions and after ischemia and reperfusion in parenchymal arterioles (PA) versus middle cerebral arteries (MCA).

Methods—

MCA and PA were dissected from male Wistar rats that were ischemic for 1 hour with 24 hours of reperfusion (n=12) or sham controls (n=12). Basal tone and reactivity to apamin (300 nmol/L), TRAM-34 (1.0 μmol/L), and nitro-
l
-arginine (0.1 mmol/L) were compared in PA and MCA pressurized to 40 mm Hg and 75 mm Hg, respectively. SK
Ca
and IK
Ca
channel mRNA expression was measured using real-time PCR.

Results—

PA developed greater basal tone than MCA (42±4% versus 19±3%;
P
<0.01). Addition of apamin and TRAM-34 increased tone of PA by 25±3% and 16±2%, respectively, whereas MCA had no response to either inhibitor. After ischemia and reperfusion, the response to nitric oxide synthase inhibition (NOS) was diminished in PA, whereas EDHF responsiveness was preserved. In addition, stimulated EDHF dilation was partially reversed by apamin and completely reversed by TRAM-34 in both control and ischemic PA. SK
Ca
and IK
Ca
channel mRNA expression was similar in PA and MCA and not altered by ischemia and reperfusion. However, IK
Ca
channel mRNA expression was 4- to 5-fold greater than SK
Ca
channels.

Conclusions—

It appears that SK
Ca
and IK
Ca
channel activity diminishes basal tone of PA, but not MCA. The preservation of EDHF responsiveness of PA after ischemia and reperfusion suggests an important role for this vasodilator under conditions when NOS is inhibited.
Classification of Regional Climate Variability in the State of California
Authors: Abatzoglou John T. , Redmond Kelly T. , Edwards Laura M.
Published: February 2009

A novel approach is presented to objectively identify regional patterns of climate variability within the state of California using principal component analysis on monthly precipitation and temperature data from a network of 195 climate stations statewide and an ancillary gridded database. The confluence of large-scale circulation patterns and the complex geography of the state result in 11 regional modes of climate variability within the state. A comparison between the station and gridded analyses reveals that finescale spatial resolution is needed to adequately capture regional modes in complex orographic and coastal settings. Objectively identified regions can be employed not only in tracking regional climate signatures, but also in improving the understanding of mechanisms behind regional climate variability and climate change. The analysis has been incorporated into an operational tool called the California Climate Tracker.
Boundary Layer Dynamics in a Simple Model for Convectively Coupled Gravity Waves
Authors: Waite Michael L. , Khouider Boualem
Published: February 2009

A simplified model of intermediate complexity for convectively coupled gravity waves that incorporates the bulk dynamics of the atmospheric boundary layer is developed and analyzed. The model comprises equations for velocity, potential temperature, and moist entropy in the boundary layer as well as equations for the free tropospheric barotropic (vertically uniform) velocity and first two baroclinic modes of vertical structure. It is based on the multicloud model of Khouider and Majda coupled to the bulk boundary layer–shallow cumulus model of Stevens. The original multicloud model has a purely thermodynamic boundary layer and no barotropic velocity mode. Here, boundary layer horizontal velocity divergence is matched with barotropic convergence in the free troposphere and yields environmental downdrafts. Both environmental and convective downdrafts act to transport dry midtropospheric air into the boundary layer. Basic states in radiative–convective equilibrium are found and are shown to be consistent with observations of boundary layer and free troposphere climatology. The linear stability of these basic states, in the case without rotation, is then analyzed for a variety of tropospheric regimes. The inclusion of boundary layer dynamics—specifically, environmental downdrafts and entrainment of free tropospheric air—enhances the instability of both the synoptic-scale moist gravity waves and nonpropagating congestus modes in the multicloud model. The congestus mode has a preferred synoptic-scale wavelength, which is absent when a purely thermodynamic boundary layer is employed. The weak destabilization of a fast mesoscale wave, with a phase speed of 26 m s−1 and coupling to deep convection, is also discussed.