bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endothelium‐mediated control of vascular tone: COX‐1 and COX‐2 products
Authors: Félétou Michel , Huang Yu , Vanhoutte Paul M 
Published: February 2011

Endothelium‐dependent contractions contribute to endothelial dysfunction in various animal models of aging, diabetes and cardiovascular diseases. In the spontaneously hypertensive rat, the archetypal model for endothelium‐dependent contractions, the production of the endothelium‐derived contractile factors (EDCF) involves an increase in endothelial intracellular calcium concentration, the production of reactive oxygen species, the predominant activation of cyclooxygenase‐1 (COX‐1) and to a lesser extent that of COX‐2, the diffusion of EDCF towards the smooth muscle cells and the subsequent stimulation of their thromboxane A2‐endoperoxide TP receptors. Endothelium‐dependent contractions are also observed in various models of hypertension, aging and diabetes. They generally also involve the generation of COX‐1‐ and/or COX‐2‐derived products and the activation of smooth muscle TP receptors. Depending on the model, thromboxane A2, PGH2, PGF2α, PGE2 and paradoxically PGI2 can all act as EDCFs. In human, the production of COX‐derived EDCF is a characteristic of the aging and diseased blood vessels, with essential hypertension causing an earlier onset and an acceleration of this endothelial dysfunction. As it has been observed in animal models, COX‐1, COX‐2 or both isoforms can contribute to these endothelial dysfunctions. Since in most cases, the activation of TP receptors is the common downstream effector, selective antagonists of this receptor should curtail endothelial dysfunction and be of therapeutic interest in the treatment of cardiovascular disorders.LINKED ARTICLES This article is part of a themed issue on Vascular Endothelium in Health and Disease. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.164.issue‐3
Cardiac ion channel modulation by the hypoglycaemic agent rosiglitazone
Authors: Hancox JC 
Published: February 2011

The hypoglycaemic thiazolidinedione rosiglitazone is used clinically in the treatment of type 2 diabetes. However, in 2010, information relating to rosiglitazone‐associated increased cardiovascular risk led the European Medicines Agency to recommend suspension of marketing authorizations for rosiglitazone‐containing anti‐diabetes drugs, while the US Food and Drug Administration recommended significant restriction on the agent's use. Two timely studies in this issue of the British Journal of Phrarmacology provide new information regarding modification of cardiac cellular electrophysiology by rosiglitazone. Szentandrássy et al. demonstrate canine ventricular action potential modification and concentration‐dependent suppression of L‐type Ca current and of transient outward and rapid delayed rectifier K currents. Jeong et al. demonstrate concentration‐dependent inhibition of recombinant Kv4.3 channels, providing mechanistic insight into the likely molecular basis of transient outward K current inhibition by the compound. Further studies using diabetic models would be of value to determine whether, in a diabetic setting, rosiglitazone modification of these channels could affect the risk of arrhythmia at clinically relevant drug concentrations.LINKED ARTICLES This article is a commentary on Szentandrássy et al., pp. 499–509 of this issue and Jeong et al., pp. 510–520 of this issue. To view these papers visit http://dx.doi.org/10.1111/j.1476‐5381.2011.01215.x and http://dx.doi.org/10.1111/j.1476‐5381.2011.01210.x
Use of School Nurse Services Among Poor Ethnic Minority Students in the Urban Pacific Northwest
Authors: Fleming Robin 
Published: February 2011

ABSTRACT
Objective: To determine whether patterns in student use of school nurse services existed according to poverty, race, and ethnicity.Design and Sample: Cross‐sectional descriptive study of 51,767 visits to school nurses made by 12,797 middle and high school students was conducted. Data were collected and analyzed by race, ethnicity, and poverty.Measures: Individual‐level quantitative data on student visits to school nurses were collected via the School Nurse Entry Database. Numbers and types of student visits were measured, along with the demographic characteristics of student visitors.Results: Poverty was the largest driver of visits to school nurses among all racial and ethnic groups. Poverty was a larger influence on White students' use of services, suggesting that factors related to race, ethnicity, or culture may have larger effects on promoting visits to school nurses by students of color. Subethnic Asian and Hispanic groups showed visit patterns that deviated from aggregated visit rates.Conclusions: Knowledge of visit patterns among poor, ethnic, and subethnic populations is important—and particularly urgent with the advent of national health reform—in informing and improving public health and school nursing policy and practice.
Psychosocial Impact of a Positive HSV‐2 Diagnosis on Adults with Unrecognized HSV‐2 Infection
Authors: Provenzale Allison , Evans Kara , Russell Julie , Hoory Tammy , Mark Hayley 
Published: February 2011

ABSTRACT
Objective: To evaluate the current research on the psychosocial impact of a positive herpes simplex virus type 2 (HSV‐2) diagnosis on asymptomatic adults.Design and Sample: A structured review of PubMed, CINAHL, and MEDLINE resulted in 8 articles published between 2000 and 2008.Measures: Articles were included if they investigated psychosocial reactions to HSV serological testing, including asymptomatic individuals, and used measurement instruments with adequate psychometric properties.Results: The studies included participants of various backgrounds, including individuals with a new HSV‐2 diagnosis concurrently receiving human immunodeficiency virus treatment, students within a university setting, and an HMO population. Current research indicates that a diagnosis of HSV‐2 does not result in persistent psychosocial morbidity. However, studies that assessed for more nuanced reactions noted an impact on quality of life related to herpes.Conclusions: Further research is needed to confirm these findings among varied populations, to explore quality of life following HSV screening, and to identify the characteristics that may make particular individuals more susceptible to adverse psychological consequences.
A New Way to Reduce Flow Disturbance in Endovascular Stents: A Numerical Study
Authors: Chen Zengsheng , Fan Yubo , Deng Xiaoyan , Xu Zaipin 
Published: February 2011

AbstractTraditional commercial stents are made of wires with square or semi‐circular cross‐sections that lead to flow disturbance, which plays an important role in the initiation and progression of restenosis. A new stent with streamlined cross‐sectional wires was proposed and researched numerically for its hemodynamic performance. Simplified models of stents with square, semi‐circular, or streamlined cross‐sectional wires were constructed numerically. Blood flows in the three models were simulated using computational fluid dynamics methods, and compared in terms of flow pattern, wall shear stress (WSS), and oscillating shear index (OSI). The results showed that when compared with the two traditional stents, the new stent with streamlined cross‐sectional wires induced almost no flow disturbance, significantly enhanced WSS, and reduced the value of OSI within the stent. The present preliminary study indicates that the optimization of the cross‐sectional shape of stent wires ought to be considered in the structural design for endovascular stents.
A randomized, double‐blind, placebo‐controlled study of the efficacy, safety, and tolerability of adjunctive carisbamate treatment in patients with partial‐onset seizures
Authors: Halford Jonathan J. , Ben‐Menachem Elinor , Kwan Patrick , Ness Seth , Schmitt Jennifer , Eerdekens Mariëlle , Novak Gerald 
Published: February 2011

SummaryPurpose:  To assess the efficacy, safety, and tolerability of adjunctive carisbamate treatment at 800 mg/day and 1,200 mg/day in patients with partial‐onset seizures (POS).Methods:  Patients ≥16 years of age with an established diagnosis of POS for ≥1 year and uncontrolled on one to three antiepileptic drugs were enrolled. Eligible patients remained on stable doses of prescribed antiepileptic drugs for an 8‐week pretreatment baseline phase and were then randomized (1:1:1) to receive carisbamate (800 mg/day or 1,200 mg/day), or placebo, for a 14‐week double‐blind phase. Primary efficacy endpoints were percentage reduction in POS frequency and responder rate (patients with ≥50% reduction in POS frequency) during the double‐blind versus baseline phase.Key Findings:  Five hundred forty‐seven patients were randomized; 540 composed the intent‐to‐treat (ITT) analysis. Four hundred thirty‐four patients (79%) completed the study. The median percent reduction from baseline to treatment phase in POS frequency was: 21% (placebo); 30% (carisbamate 800 mg); 36% (carisbamate 1,200 mg), and 32% (combined carisbamate doses). The combined carisbamate dose group was not significantly different from placebo for the median percent reduction of POS frequency (p = 0.20) or responder rate (p = 0.18). Therefore, the difference from placebo for the individual carisbamate dose groups was also considered nonsignificant, based on a prespecified step‐down analysis. Dizziness was the most common treatment‐emergent adverse event, with a higher incidence (≥5% difference) in the combined carisbamate group (31%) than placebo (9%); the incidence was higher with carisbamate 1,200 mg (32%, n = 58) than with carisbamate 800 mg (30%, n = 53).Significance:  Adjunctive carisbamate therapy in patients with POS did not demonstrate efficacy across the dose range assessed versus placebo. No new safety findings were observed.
Seizure outcome in infantile spasms—A retrospective study
Authors: Mohamed Basheer Peer , Scott Rod C. , Desai Nivedita , Gutta Pranathi , Patil Shekhar 
Published: February 2011

SummaryPurpose:  Prior to the United Kingdom Infantile Spasms Study (UKISS), our practice was to initiate vigabatrin for infantile spasms. However, since then we tend to use steroids as first‐line agent for infantile spasms. Herein we compare seizure‐free outcomes in children with infantile spasms on steroid therapy or vigabatrin therapy.Methods:  This was a retrospective case study over 8 years of children with infantile spasms who were treated at our center. A positive response to therapy was defined as a two‐week spasm‐free interval.Key Findings:  Of the 98 children presenting to us, 75 were included for this study. The ratio of cryptogenic to symptomatic spasms was 24:51. The response rate for steroid therapy was 61.1% and 42.5% for vigabatrin. Cessation of spasms was achieved faster in the group receiving steroids. Both groups had similar relapse rates. Steroids had significantly better response in the cryptogenic group, whereas in the symptomatic group both the medications were equally effective. Cryptogenic spasms have a better neurodevelopmental outcome. Early introduction of therapy for spasms did not predict a good neurodevelopmental outcome. Seventy‐eight percent of children with spasms had seizures of other types at 12 months follow‐up.Significance:  At our center, steroids are now the preferred choice for initial therapy of infantile spasms. This is likely to have been a beneficial change, particularly for children with cryptogenic spasms. Spasms in 25% of the patients tend to be refractory, and the majority of patients from the cohort continue to have epilepsy with motor and cognitive disabilities.
The adverse event profile of pregabalin: A systematic review and meta‐analysis of randomized controlled trials
Authors: Zaccara Gaetano , Gangemi Pierfranco , Perucca Piero , Specchio Luigi 
Published: February 2011

SummaryPurpose:  Despite the widespread use of antiepileptic drugs (AEDs) across different neurologic and psychiatric disorders, no study has systematically reviewed all available randomized controlled trials (RCTs) of a given AED to fully uncover its tolerability profile.We aimed at identifying treatment emergent adverse events (AEs) associated with pregabalin through a systematic review and meta‐analysis of all available RCTs. We also assessed the association between serious AEs and pregabalin, and investigated whether pregabalin AEs display a dose–response relationship.Methods:  We searched MEDLINE, EMBASE, and Cochrane CENTRAL to February 2010 for RCTs. Additional studies were identified from reference lists of retrieved papers and from online clinical databases. We selected placebo‐controlled, double‐blind RCTs investigating the therapeutic effects of pregabalin in adults with any condition. Studies had to include at least 20 subjects per arm and have a duration of at least 4 weeks. AEs were assessed for their association with pregabalin after identification/exclusion of synonyms, rare AEs, and nonassessable AEs due to methodologic limitations. We used relative risks (RRs) to assess the association of any [99% confidence intervals (CIs)] or serious AEs (95% CIs) with pregabalin, and risk differences (RDs, 95% CIs) to investigate dose–response relationships of pregabalin AEs.Key findings:  Thirty‐eight RCTs were included in our study. Of 39 AEs, 20 (51%) were significantly associated with pregabalin (dizziness, vertigo, incoordination, balance disorder, ataxia, diplopia, blurred vision, amblyopia, tremor, somnolence, confusional state, disturbance in attention, thinking abnormal, euphoria, asthenia, fatigue, edema, peripheral edema, dry mouth, constipation). The highest RRs were found for cognition/coordination AEs. There was no significant association between serious AEs and pregabalin. There was a selective dose–response pattern in the onset of pregabalin AEs, with certain AEs appearing at lower doses than others.Significance:  Individuals starting treatment with pregabalin are at increased risk for several AEs, particularly those affecting cognition/coordination. Pregabalin AEs appear according to a selective dose–response pattern, possibly reflecting the severity of dysfunction of distinct anatomic structures. These findings may aid clinicians in providing better patient management, and support the value of including in meta‐analyses of AED tolerability profiles RCTs performed in different conditions.
A population‐based study of long‐term outcomes of cryptogenic focal epilepsy in childhood: Cryptogenic epilepsy is probably not symptomatic epilepsy
Authors: Wirrell Elaine C. , Grossardt Brandon R. , So Elson L. , Nickels Katherine C. 
Published: February 2011

SummaryPurpose:  To compare long‐term outcome in a population‐based group of children with cryptogenic versus symptomatic focal epilepsy diagnosed from 1980 to 2004 and to define the course of epilepsy in the cryptogenic group.Methods:  We identified all children residing in Olmsted County, MN, 1 month through 17 years, with newly diagnosed, nonidiopathic focal epilepsy from 1980 to 2004. Children with idiopathic partial epilepsy syndromes were excluded. Medical records were reviewed to determine etiology, results of imaging and EEG studies, treatments used, and long‐term outcome. Children were defined as having symptomatic epilepsy if they had a known genetic or structural/metabolic etiology, and as cryptogenic if they did not.Key Findings:  Of 359 children with newly diagnosed epilepsy, 215 (60%) had nonidiopathic focal epilepsy. Of these, 206 (96%) were followed for >12 months. Ninety‐five children (46%) were classified as symptomatic. Median follow‐up from diagnosis was similar in both groups, being 157 months (25%, 75%: 89, 233) in the cryptogenic group versus 134 months (25%, 75%: 78, 220) in the symptomatic group (p = 0.26). Of 111 cryptogenic cases, 66% had normal cognition. Long‐term outcome was significantly better in those with cryptogenic versus symptomatic etiology (intractable epilepsy at last follow‐up, 7% vs. 40%, p < 0.001; seizure freedom at last follow‐up, 81% vs. 55%, p < 0.001). Of those who achieved seizure freedom at final follow‐up, 68% of the cryptogenic group versus only 46% of the symptomatic group were off antiepileptic medications (p = 0.01). One‐third of the cryptogenic group had a remarkably benign disorder, with no seizures seen after initiation of medication, or in those who were untreated, after the second afebrile seizure. A further 5% had seizures within the first year but remained seizure‐free thereafter. With the exception of perinatal complications, which predicted against seizure remission, no other factors were found to significantly predict outcome in the cryptogenic group.Significance:  More than half of childhood nonidiopathic localization‐related epilepsy is cryptogenic. This group has a significantly better long‐term outcome than those with a symptomatic etiology, and should be distinguished from it.
Isocitrate Dehydrogenase 1 Analysis Differentiates Gangliogliomas from Infiltrative Gliomas
Authors: Horbinski Craig , Kofler Julia , Yeaney Gabrielle , Camelo‐Piragua Sandra , Venneti Sriram , Louis David N. , Perry Arie , Murdoch Geoffrey , Nikiforova Marina 
Published: February 2011

AbstractRecent work has identified novel point mutations in isocitrate dehydrogenase 1 (IDH1) in the majority of the World Health Organization grades II and III infiltrative gliomas and secondary grade IV glioblastomas. Gangliogliomas consist of neoplastic ganglion and glial cells and, in contrast to infiltrative gliomas, are generally indolent. Yet distinguishing between a ganglioglioma and an infiltrative glioma with admixed gray matter can be difficult, perhaps accounting for some “gangliogliomas” that ultimately show aggressive behavior. In this multi‐institutional study, 98 cases originally diagnosed as ganglioglioma were analyzed for IDH1 mutations, 86 of which had follow‐up data available. Eight cases (8.2%) were positive for R132H IDH1 mutations; six had silent IDH2 mutations and two had nonsense IDH2 mutations. The presence of mutant IDH1 in gangliogliomas correlated with a greater risk of recurrence (P = 0.0007) and malignant transformation and/or death (P < 0.0001) compared with tumors that were IDH1 wild type. Furthermore, the age of patients with IDH1‐mutant gangliogliomas was higher than those without mutations (25.5 vs. 46.1 years, P = 0.0033). IDH1/2 testing of tumors suspected of being gangliogliomas may therefore be advisable, particularly in the adult population.
Eco‐evolutionary effects on population recovery following catastrophic disturbance
Authors: Weese Dylan J. , Schwartz Amy K. , Bentzen Paul , Hendry Andrew P. , Kinnison Michael T. 
Published: February 2011

AbstractFine‐scale genetic diversity and contemporary evolution can theoretically influence ecological dynamics in the wild. Such eco‐evolutionary effects might be particularly relevant to the persistence of populations facing acute or chronic environmental change. However, experimental data on wild populations is currently lacking to support this notion. One way that ongoing evolution might influence the dynamics of threatened populations is through the role that selection plays in mediating the ‘rescue effect’, the ability of migrants to contribute to the recovery of populations facing local disturbance and decline. Here, we combine experiments with natural catastrophic events to show that ongoing evolution is a major determinant of migrant contributions to population recovery in Trinidadian guppies (Poecilia reticulata). These eco‐evolutionary limits on migrant contributions appear to be mediated by the reinforcing effects of natural and sexual selection against migrants, despite the close geographic proximity of migrant sources. These findings show that ongoing adaptive evolution can be a double‐edged sword for population persistence, maintaining local fitness at a cost to demographic risk. Our study further serves as a potent reminder that significant evolutionary and eco‐evolutionary dynamics might be at play even where the phenotypic status quo is largely maintained generation to generation.
δ18O and chemical composition of Libyan Desert Glass, country rocks, and sands: New considerations on target material
Authors: LONGINELLI Antonio , SIGHINOLFI Giampaolo , De MICHELE Vincenzo , SELMO Enricomaria 
Published: February 2011

Abstract–Oxygen isotope and chemical measurements were carried out on 25 samples of Libyan Desert Glass (LDG), 21 samples of sandstone, and 3 of sand from the same area. The δ18O of LDG samples range from 9.0‰ to 11.9‰ (Vienna Standard Mean Ocean Water [VSMOW]); some correlations between isotope data and typological features of the LDG samples are pointed out. The initial δ18O of a bulk parent material may be slightly increased by fusion due to the loss of isotopically light pore water with no isotope exchange with oxygen containing minerals. Accordingly, the δ18O of the bulk parent material of LDG may have been about 9.0 ± 1‰ (VSMOW). The measured bulk sandstone and sand samples have δ18O values ranging from 12.6‰ to 19.5‰ and are consequently ruled out as parent materials, matching the results of previous studies. However, separated quartz fractions have δ18O values compatible with the LDG values suggesting that the modern surface sand inherited quartz from the target material. This hypothesis fits previous findings of lechatelierite and baddeleyite in these materials. As the age of the parent material reported in previous studies is Pan‐African, we measured the δ18O values of bulk rock and quartz from intrusives of Pan‐African age and the results obtained were compatible with the LDG values. The main element abundances (Fe, Mg, Ca, K, Na) in our LDG samples conform to previous estimates; Fe, Mg, and K tend to be higher in heterogeneous samples with dark layers. The hypothesis of a low‐altitude airburst involving silica‐rich surface materials deriving from weathered intrusives of Pan‐African age, partially melted and blown over a huge surface by supersonic winds matches the results obtained.
Polypharmacy and patterns in drug prescribing at a primary healthcare centre in the Riyadh region of Saudi Arabia
Authors: Asiri Yousif A , Al-Arifi Mohamed N 
Published: February 2011

Abstract

Objective
To elucidate the various patterns in drug prescribing in a non-Ministry of Health-affiliated primary healthcare centre model (Riyadh Kharj Military Hospital) in Saudi Arabia.

Methods
A retrospective analysis of pharmacy records of the Riyadh Kharj Military Hospital was undertaken. A total of 4781 prescriptions archived over a period of 6 months (January–June 2001) were statistically analysed using Statistical Package for the Social Sciences (SPSS). Number, types, therapeutic duration and distribution of drugs were evaluated. Age distribution and documentation adequacy were also reviewed and monitored. Therapeutic classification of drugs was carried out according to the British National Formulary system.

Key findings
Of the total prescriptions, 47.8% were for male patients and 50.1% for females. Prescriptions for the paediatric population accounted for 19.5% whereas 13.7% of drugs were prescribed to the geriatric cohort. A mean of 2.7 ± 1.6 drugs were prescribed per patient. In multidrug prescriptions, 32.3% contained two drugs and 22.1% prescriptions had four drugs or more. Mono-drug prescriptions accounted for 21.6% of prescriptions. Paracetamol (13.9%) was the most commonly prescribed drug followed by multivitamins and cough syrups with 5.0 and 3.7%, respectively. The most common therapeutic classes of drugs prescribed were analgesics, antipyretics, antihistamines, and vitamins and minerals, making up a third of all prescriptions. Dosage form, dose and routes of administration were not present in 21.7, 8.8 and 99.6%, respectively.

Conclusion
Polypharmacy appears to be a problem in primary health care, which requires stricter pharmacovigilance and constant reviewing. We recommend the establishment of an efficient local prescribing policy through an effective practice-based Pharmacy and Therapeutic Committee, training in prescribing to be introduced in medical schools and the lending of support to continuous education programmes targeting prescribing skills.