bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long‐term effects of losartan on structure and function of the thoracic aorta in a mouse model of Marfan syndrome
Authors: Yang HH Clarice , Kim Jong Moo , Chum Elliott , van Breemen Cornelis , Chung Ada WY 
Published: October 2009

Background and purpose:  During development of thoracic aortic aneurysms in a mouse model of Marfan syndrome, upregulation of matrix metalloproteinase (MMP)‐2 and ‐9 was accompanied by compromised aortic constriction and endothelium‐dependent relaxation. Losartan has been proposed for the prevention of thoracic aortic aneurysm. We hypothesized that losartan would suppress MMP‐2/‐9 activation and improve aortic vasomotor function in this model.Experimental approach:  A well‐characterized mouse model of Marfan syndrome (Fbn1C1039G/+) was used. Starting at 6 weeks old, Marfan mice were untreated or given losartan (0.6 g·L−1 in drinking water, n= 30). The littermate Fbn1+/+ mice served as control. Thoracic aortas were studied at 3, 6 and 9 months by histology and by contractility assays in isolated segments in vitro.Key results:  Losartan improved elastic fibre organization and increased aortic breaking stress. Losartan reduced the activity and protein expression of MMP‐2 and MMP‐9 at all ages. Aortic constriction in response to membrane depolarization or phenylephrine was increased by losartan at 3 and 9 months by 100–200%. Active force of aortic smooth muscle was also increased at 6 and 9 months. Acetylcholine‐induced endothelium‐dependent relaxation was improved by 30% after 3 months of losartan treatment, but such improvement disappeared with longer duration of treatment, accompanied by reduced phosphorylation of endothelial nitric oxide (NO) synthaseSer1177, AktThr308 and AktSer473, compared with the control.Conclusions and implications:  Losartan improved the contractile function of aorta and reduced MMP activation. However, the endothelial NO pathway remained suppressed in the thoracic aorta during losartan treatment, which might limit its long‐term benefits in Marfan syndrome.
HIT‐6 and MIDAS as Measures of Headache Disability in a Headache Referral Population
Authors: Sauro Khara M. , Rose Marianne S. , Becker Werner J. , Christie Suzanne N. , Giammarco Rose , Mackie Gordon F. , Eloff Arnoldas G. , Gawel Marek J. 
Published: October 2009

(Headache 2010;50:383‐395)Objective.— The objective of this study was to compare the headache impact test (HIT‐6) and the migraine disability assessment scale (MIDAS) as clinical measures of headache‐related disability.Background.— The degree of headache‐related disability is an important factor in treatment planning. Many quality of life and headache disability measures exist but it is unclear which of the available disability measures is the most helpful in planning and measuring headache management.Methods.— We compared HIT‐6 and MIDAS scores from 798 patients from the Canadian Headache Outpatient Registry and Database (CHORD). Correlation and regression analyses were used to examine the relationships between the HIT‐6 and MIDAS total scores, headache frequency and intensity, and Beck Depression Inventory (BDI‐II) scores.Results.— A positive correlation was found between HIT‐6 and MIDAS scores (r = 0.52). The BDI‐II scores correlated equally with the HIT‐6 and the MIDAS (r = 0.42). There was a non‐monotonic relationship between headache frequency and the MIDAS, and a non‐linear monotonic relationship between headache frequency and the HIT‐6 (r = 0.24). The correlation was higher between the intensity and the HIT‐6 scores (r = 0.46), than MIDAS (r = 0.26) scores. Seventy‐nine percent of patients fell into the most severe HIT‐6 disability category, compared with the 57% of patients that fell into the most severe MIDAS disability category. Significantly more patients were placed in a more severe category with the HIT‐6 than with the MIDAS (McNemar chi‐square = 191 on 6 d.f., P < .0001).Conclusions.— The HIT‐6 and MIDAS appear to measure headache‐related disability in a similar fashion. However, some important differences may exist. Headache intensity appears to influence HIT‐6 score more than the MIDAS, whereas the MIDAS was influenced more by headache frequency. Using the HIT‐6 and MIDAS together may give a more accurate assessment of a patient's headache‐related disability.
Noxious Inhibition of Temporal Summation is Impaired in Chronic Tension‐Type Headache
Authors: Cathcart Stuart , Winefield Anthony H. , Lushington Kurt , Rolan Paul 
Published: October 2009

(Headache 2010;50:403‐412)Objective.— To examine effects of stress on noxious inhibition and temporal summation (TS) in tension‐type headache.Background.— Stress is the most commonly reported trigger of a chronic tension‐type headache (CTH) episode; however, the mechanisms underlying this are unclear. Stress affects pain processing throughout the central nervous system, including, potentially, mechanisms of TS and diffuse noxious inhibitory controls (DNIC), both of which may be abnormal in CTH sufferers (CTH‐S). No studies have examined TS of pressure pain or DNIC of TS in CTH‐S to date. Similarly, effects of stress on TS or DNIC of TS have not been reported in healthy subjects or CTH‐S to date.Methods.— The present study measured TS and DNIC of TS in CTH‐S and healthy controls (CNT) exposed to an hour‐long stressful mental task, and in CTH‐S exposed to an hour‐long neutral condition. TS was elicited at finger and shoulder via 10 pulses from a pressure algometer, applied before and during stimulation from an occlusion cuff at painful intensity.Results.— Algometer pain ratings increased more in the CTH compared with the CNT group, and were inhibited during occlusion cuff more in the CNT compared with CTH groups. Task effects on TS or DNIC were not significant.Conclusions.— The results indicate increased TS to pressure pain and impaired DNIC of TS in CTH‐S. Stress does not appear to aggravate abnormal TS or DNIC mechanisms in CTH‐S.
Urinary 6‐Sulphatoxymelatonin Levels Are Depressed in Chronic Migraine and Several Comorbidities
Authors: Masruha Marcelo R. , Lin Jaime , De Souza Vieira Domingos S. , Minett Thais S.C. , Cipolla‐Neto José , Zukerman Eliova , Vilanova Luiz C.P. , Peres Mario F.P. 
Published: October 2009

(Headache 2010;50:413‐419)Objective.— To assess urinary 6‐sulphatoxymelatonin levels in a large consecutive series of patients with migraine and several comorbidities (chronic fatigue, fibromyalgia, insomnia, anxiety, and depression) as compared with controls.Background.— Urine analysis is widely used as a measure of melatonin secretion, as it is correlated with the nocturnal profile of plasma melatonin secretion. Melatonin has critical functions in human physiology and substantial evidence points to its importance in the regulation of circadian rhythms, sleep, and headache disorders.Methods.— Urine samples were collected into a single plastic container over a 12‐hour period from 8:00 pm to 8:00 am of the next day, and 6‐sulphatoxymelatonin was measured by quantitative ELISA. All of the patients were given a detailed questionnaire about headaches and additionally answered the following questionnaires: Chalder fatigue questionnaire, Epworth somnolence questionnaire, State‐Trait Anxiety Inventory, and the Beck Depression Inventory.Results.— A total of 220 subjects were evaluated – 73 (33%) had episodic migraine, 73 (33%) had chronic migraine, and 74 (34%) were enrolled as control subjects. There was a strong correlation between the concentration of 6‐sulphatoxymelatonin detected and chronic migraine. Regarding the comorbidities, this study objectively demonstrates an inverse relationship between 6‐sulphatoxymelatonin levels and depression, anxiety, and fatigue.Conclusions.— To our knowledge, this is the first study to evaluate the relationship between the urinary concentration of melatonin and migraine comorbidities. These results support hypothalamic involvement in migraine pathophysiology.
Neocortical seizure foci localization by means of a directed transfer function method
Authors: Wilke Christopher , Van Drongelen Wim , Kohrman Michael , He Bin 
Published: October 2009

SummaryPurpose:  Determination of the origin of extratemporal neocortical onset seizures is often challenging due to the rapid speed at which they propagate throughout the cortex. Typically, these patients are poor surgical candidates and many times experience recurrences of seizure activity following resection of the assumed seizure focus.Methods:  We applied a causal measurement technique—the directed transfer function (DTF)—in an effort to determine the cortical location responsible for the propagation of the seizure activity. Intracranial seizure recordings were obtained from a group of 11 pediatric patients with medically intractable neocortical‐onset epilepsy. Time windows were selected from the recordings following onset of the ictal activity. The DTF was applied to the selected time windows, and the frequency‐specific statistically significant source activity arising from each cortical recording site was quantified. The DTF‐estimated source activity was then compared with the seizure‐onset zone(s) identified by the epileptologists.Results:  In an analysis of the 11 pediatric patients, the DTF was shown to identify estimated ictal sources that were highly correlated with the clinically identified foci. In addition, it was observed that in the patients with multiple ictal foci, the topography of the casual source activity from the analyzed seizures was associated with the separate clinically identified seizure‐onset zones.Discussion:  Although localization of neocortical‐onset seizures is typically challenging, the causal measures employed in this study—namely the directed transfer function—identified generators of the ictal activity that were highly correlated with the cortical regions identified as the seizure‐onset zones by the epileptologists. This technique could prove useful in the identification of seizure‐specific propagation pathways in the presurgical evaluation of patients with epilepsy.
Pathologic cardiac repolarization in pharmacoresistant epilepsy and its potential role in sudden unexpected death in epilepsy: A case–control study
Authors: Surges Rainer , Adjei Patrick , Kallis Constantinos , Erhuero Joy , Scott Catherine A. , Bell Gail S. , Sander Josemir W. , Walker Matthew C. 
Published: October 2009

SummaryPurpose:  To determine whether abnormal cardiac repolarization and other electrocardiography (ECG) predictors for cardiac mortality occur in epilepsy patients and whether they are associated with an increased risk for sudden unexpected death in epilepsy (SUDEP).Methods:  In a matched‐pair case–control study, recordings of adult patients with pharmacoresistant focal epilepsies who died from SUDEP and who had previously had presurgical video‐EEG (electroencephalography) telemetry were reviewed. Living controls were matched for age, gender, and date of admission for video‐EEG telemetry. Periictal heart rate (HR), corrected QT interval (QTc), postictal HR recovery, HR variability, and cardiac rhythm were assessed. QT dispersion was analyzed with 12‐lead ECG.Results:  A total of 38 patients (19 per group) had 91 recorded seizures. QTc was prolonged above pathologic upper limits in 9 of 89 seizures and 5 of 38 patients. Nine of 34 patients displayed pathologic QT dispersion. Presence of neither pathologic cardiac repolarization nor other ECG features were specifically associated with SUDEP. SUDEP patients were, however, more likely to lack pathologic cerebral magnetic resonance imaging (MRI) findings, less likely to experience antiepileptic drug reduction during telemetry, and had more secondarily generalized tonic–clonic seizures (SGTCS) per year.Discussion:  Our study did not reveal a clear‐cut ECG predictor for SUDEP. Pathologic cardiac repolarization is not uncommon in adult patients with pharmacoresistant focal epilepsy and could favor occurrence of fatal tachyarrhythmia as one plausible cause for SUDEP. SGTCS are a risk factor for SUDEP, have, as compared to complex‐partial seizures, a greater, unfavorable impact on heart activity, and may thereby additionally compromise cardiac function.
Comparison of antiepileptic drug prescribing in children in three European countries
Authors: Hsia Yingfen , Neubert Antje , Sturkenboom Miriam C.J.M. , Murray Macey L. , Verhamme Katia M.C. , Sen Fatma , Giaquinto Carlo , Ceci Adriana , Wong Ian C.K. ,   on behalf of the TEDDY Network of Excellence
Published: October 2009

SummaryPurpose:  Antiepileptic drug (AED) use in young people is increasing. However, evidence of its use at a multinational level is limited. This study aims to characterize AED prescribing in the young in three European countries and to assess the capacity of drug safety surveillance.Methods:  A retrospective cohort study was conducted in 2001–2005 using primary care databases: PEDIANET (Italy, 0–11 years), IPCI (The Netherlands, 0–18 years), and IMS Disease Analyzer (United Kingdom, 0–18 years). Prescribing prevalence was calculated by country, patient age, and drug type.Results:  In 2005, AED prevalence in children (0–11 years) was highest in Italy [3.9 subjects/1,000 person‐years (PY)] followed by the United Kingdom (3.0 subjects/1,000 PY) and The Netherlands (2.2 subjects/1,000 PY). Over the study period, prescribing prevalence in 0–11 year olds was stable in all countries. In contrast, a steady rise of AED prevalence was observed in adolescents (12–18 years) in the United Kingdom (p = 0.0003) but not in The Netherlands (p = 0.88). All countries showed a slight increase in prevalence for newer AEDs. Simultaneously, the prevalence of conventional AEDs decreased in The Netherlands and Italy, but not in the United Kingdom. In 2005, lamotrigine use was highest in The Netherlands and the United Kingdom, whereas topiramate was favored in Italy.Discussion:  In Europe, conventional AEDs are still the main treatment choice for children with epilepsy, and the use of newer AEDs remains low. Our study highlights a lack of research capacity to conduct multinational AED safety studies in children. Further work should explore large databases and other health care settings to meet these research needs.
Cerebrospinal fluid levels of the endocannabinoid anandamide are reduced in patients with untreated newly diagnosed temporal lobe epilepsy
Authors: Romigi Andrea , Bari Monica , Placidi Fabio , Marciani M. Grazia , Malaponti Marilena , Torelli Federico , Izzi Francesca , Prosperetti Chiara , Zannino Silvana , Corte Francesca , Chiaramonte Carlo , Maccarrone Mauro 
Published: October 2009

SummaryPurpose:  The endocannabinoid system is involved in excitatory/inhibitory balance mechanisms within the central nervous system (CNS). Growing evidence shows that its perturbation leads to development of epileptic seizures in experimental models, thus indicating that endocannabinoids play an intrinsic protective role in suppressing pathologic neuronal excitability. Experimental data also demonstrate that the endocannabinoid anandamide (AEA) can antagonize epileptic discharges in hippocampal tissue. The objective of our study was to measure endocannabinoids levels in the cerebrospinal fluid (CSF) of drug‐naive patients affected by temporal lobe epilepsy (TLE).Methods:  We measured the levels of both AEA and the other endocannabinoid, 2‐arachidonoylglycerol (2‐AG), in the CSF of drug‐naive patients with TLE.Results:  A significant reduction of AEA was found in the CSF of patients with compared with healthy controls (epileptic patients = 2.55 ± 1.78 pmol/ml; healthy controls = 11.65 ± 7.53 pmol/ml; n = 9 for both groups, p < 0.01). 2‐AG levels, however, were not affected (epileptic patients = 209.5 ± 146.56; healthy controls = 159.6 ± 110.2) (n = 6 for both groups, p = 0.48).Discussion:  Our findings seem to be consistent with experimental evidence demonstrating a significant prevention of epileptic seizures induced by endocannabinoids in models of epilepsy. Furthermore, they support the hypothesis that AEA may be involved in its pathogenesis, suggesting a hypothetical primary impairment of the endocannabinoid system in untreated TLE. The actual role of this in vivo dysregulation still remains unclear.
Contralateral MRI abnormalities in candidates for hemispherectomy for refractory epilepsy
Authors: Hallbook Tove , Ruggieri Paul , Adina Chirla , Lachhwani Deepak K. , Gupta Ayaj , Kotagal Prakash , Bingaman William E. , Wyllie Elaine 
Published: October 2009

SummaryPurpose:  To assess the impact of contralateral magnetic resonance imaging (MRI) findings on seizure outcome after hemispherectomy for refractory epilepsy.Methods:  We retrospectively reviewed 110 children, 0.4–18 (median 5.9) years of age, who underwent hemispherectomy for severe refractory epilepsy at Cleveland Clinic Children’s Hospital. In children with contralateral (as well as ipsilateral) MRI findings appreciated preoperatively, the decision to proceed to surgery was based on other features concordant with the side with the most severe MRI abnormality, including ipsilateral epileptiform discharges, lateralizing seizure semiology, and side of hemiparesis.Results:  We retrospectively observed contralateral MRI abnormalities (predominantly small hemisphere, white matter loss or abnormal signal, or sulcation abnormalities) in 81 patients (74%), including 31 of 43 (72%) with malformations of cortical development (MCD), 31 of 42 (73%) with perinatal injury from infarction or hypoxia, and 15 of 25 (60%) with Rasmussen’s encephalitis, Sturge‐Weber syndrome, or posttraumatic encephalomalacia. Among 84 children (76%) with lesions that were congenital or acquired pre‐ or perinatally, 67 (83%) had contralateral MRI abnormalities (p = 0.02). Contralateral findings were subjectively judged to be mild or moderate in 70 (86%). At follow‐up 12–84 (median 24) months after surgery, 79% of patients with contralateral MRI abnormalities were seizure‐free compared to 83% of patients without contralateral MRI findings, with no differences based on etiology group or type or severity of contralateral MRI abnormality.Discussion:  MRI abnormalities, usually mild to moderate in severity, were seen in the contralateral hemisphere in the majority of children who underwent hemispherectomy for refractory epilepsy due to various etiologies, especially those that were congenital or early acquired. The contralateral MRI findings, always much less prominent than those in the ipsilateral hemisphere, did not correlate with seizure outcome and may not contraindicate hemispherectomy in otherwise favorable candidates.
A comparison of two fMRI methods for predicting verbal memory decline after left temporal lobectomy: Language lateralization versus hippocampal activation asymmetry
Authors: Binder Jeffrey R. , Swanson Sara J. , Sabsevitz David S. , Hammeke Thomas A. , Raghavan Manoj , Mueller Wade M. 
Published: October 2009

SummaryPurpose:  Language lateralization measured by preoperative functional magnetic resonance imaging (fMRI) was shown recently to be predictive of verbal memory outcome in patients undergoing left anterior temporal lobe (L‐ATL) resection. The aim of this study was to determine whether language lateralization or functional lateralization in the hippocampus is a better predictor of outcome in this setting.Methods:  Thirty L‐ATL patients underwent preoperative language fMRI, preoperative hippocampal fMRI using a scene encoding task, and pre‐ and postoperative neuropsychological testing. A group of 37 right ATL (R‐ATL) surgery patients was included for comparison.Results:  Verbal memory decline occurred in roughly half of the L‐ATL patients. Preoperative language lateralization was correlated with postoperative verbal memory change. Hippocampal activation asymmetry was strongly related to side of seizure focus and to Wada memory asymmetry but was unrelated to verbal memory outcome.Discussion:  Preoperative hippocampal activation asymmetry elicited by a scene encoding task is not predictive of verbal memory outcome. Risk of verbal memory decline is likely to be related to lateralization of material‐specific verbal memory networks, which are more closely correlated with language lateralization than with overall asymmetry of episodic memory processes.
Vanoxerine: Cellular Mechanism of a New Antiarrhythmic
Authors: LACERDA ANTONIO E. , KURYSHEV YURI A. , YAN GAN‐XIN , WALDO ALBERT L. , BROWN ARTHUR M. 
Published: October 2009

Cellular Electrophysiology of Vanoxerine. Introduction: There remains an unmet need for safe and effective antiarrhythmic drugs, especially for the treatment of atrial fibrillation. Vanoxerine is a drug that is free of adverse cardiac events in normal volunteers, yet is a potent blocker of the hERG (hKv11.1) cardiac potassium channel. Consequently,we hypothesized that vanoxerine might also be a potent blocker of cardiac calcium (Ca) and sodium (Na) currents, and would not affect transmural dispersion of repolarization.
Methods:
The whole cell patch clamp technique was used to measure currents from cloned ion channels overexpressed in stable cell lines and single ventricular myocytes. We measured intracellular action potentials from canine ventricular wedges and Purkinje fibers using sharp microelectrode technique.
Results:
We found that vanoxerine was a potent hKv11.1 blocker, and at submicromolar concentrations, it blocked Ca and Na currents in a strongly frequency‐dependent manner. In the canine ventricular wedge preparation vanoxerine did not significantly affect transmural action potential waveforms, QT interval or transmural dispersion of repolarization.
Conclusions:
Vanoxerine (1) is a potent blocker of cardiac hERG, Na and Ca channels; (2) block is strongly frequency‐dependent especially for Na and Ca channels; and (3) transmural dispersion of ventricular repolarization is unaffected. The multichannel block and repolarization uniformity resemble the effects of amiodarone, the exemplar atrial fibrillation drug. Vanoxerine is a completely different chemical and has none of amiodarone's toxic effects. Vanoxerine has characteristics of a potentially effective and safe antiarrhythmic. (J Cardiovasc Electrophysiol, Vol. 21, pp. 301–310, March 2010)
Long‐Term Outcomes of Inducible Very Fast Ventricular Tachycardia (Cycle Length 200–250 ms) in Patients With Ischemic Cardiomyopathy
Authors: KUMAR SAURABH , SIVAGANGABALAN GOPAL , CHOI MAN‐CHUN , EIPPER VICKI , THIAGALINGAM ARAVINDA , KOVOOR PRAMESH 
Published: October 2009

Very Fast Ventricular Tachycardia. Background: The long‐term outcomes of patients with inducible very fast ventricular tachycardia (VFVT) of cycle length (CL) 200 to 250 ms have not been well studied.
Methods: Consecutive patients with ischemic cardiomyopathy with a left ventricular ejection fraction (LVEF) of ≤40% (n = 300) underwent programmed ventricular stimulation (PVS) and were divided into 4 groups based on results of the study. Group A were noninducible, had induced ventricular fibrillation (VF), or polymorphic VT (CL < 200 ms); group B had inducible VFVT (200–250 ms); group C had inducible fast ventricular tachycardia (FVT; CL 251–320 ms); and group D had inducible slow VT (CL >320 ms). The primary endpoint was spontaneous ventricular arrhythmia or sudden death.
Results:
The mean age was 63 ± 12 years and mean LVEF was 29 ± 7%. At mean follow‐up of 38 ± 25 months (median 30 months), the primary endpoint rate was 6.6%, 34%, 44%, and 71% in groups A, B C, and D, respectively (P < 0.001). Neither mode of induction of VT nor LVEF altered the observed pattern in the primary endpoint. There was no significant difference in the primary endpoint among implanted cardioverter defibrillator recipients in groups B and C (38% vs 45%, P = 0.43). Adjusted hazard ratios for the primary endpoint compared to group A were 3.2, 3.5, and 7.0 in groups B, C, and D, respectively (P < 0.05).
Conclusions:
Inducible VFVT (200–250 ms) is a clinically significant arrhythmia with adverse long‐term outcomes and should not be considered a nonspecific finding of PVS. (J Cardiovasc Electrophysiol, Vol. 21, pp. 262–269, March 2010)