bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tobacco smoke affects expression of peroxisome proliferator‐activated receptor‐γ in monocyte/macrophages of patients with coronary heart disease
Authors: Amoruso A , Gunella G , Rondano E , Bardelli C , Fresu LG , Ferrero V , Ribichini F , Vassanelli C , Brunelleschi S 
Published: October 2009

Background and purpose: Tobacco smoke represents a relevant risk factor for coronary heart disease (CHD). Although peroxisome proliferator‐activated receptor (PPAR)γ activation reduces inflammation and atherosclerosis, expression of PPARγ in cells and its modulation by smoking are poorly investigated. We previously reported that monocyte/macrophages from healthy smokers exhibited an enhanced constitutive expression of PPARγ. Here, we evaluated PPARγ expression and basal cytokine release in monocytes and monocyte‐derived macrophages (MDMs) from 85 CHD patients, classified by their smoking habit (smokers, non‐smokers and ex‐smokers), and assessed the role of PPARγ ligands in this context.Experimental approach: PPARγ protein was detected by Western blot and semi‐quantified by PPARγ/β‐actin ratio; cytokine release was measured byelisaand nuclear factor‐kappaB (NF‐κB) translocation by electrophoretic mobility shift assays.Key results: As compared to the other groups, MDMs from smoker CHD patients exhibited a reduced PPARγ/β‐actin ratio and an increased spontaneous release of tumour necrosis factor‐α (TNF‐α) and interleukin‐6, but with no major variations in monocytes. In cells from selected CHD patients, rosiglitazone inhibited TNF‐α release and NF‐κB translocation induced by phorbol‐12‐myristate 13‐acetate. The selective PPARγ antagonist GW9662 reversed these effects, with some variations related to smoking habit.Conclusions and implications: In CHD patients, exposure to tobacco smoke profoundly affected PPARγ expression, and this was related to levels of secretion of pro‐inflammatory cytokines. MDMs from CHD smokers showed the lowest PPARγ expression and released more inflammatory cytokines. Moreover, rosiglitazone's ability to inhibit cytokine release and its reversal by GW9662 clearly indicated PPARγ involvement in these changes in CHD patients.
Protective role of the antidiabetic drug metformin against chronic experimental pulmonary hypertension
Authors: Agard C , Rolli‐Derkinderen M , Dumas‐de‐La‐Roque E , Rio M , Sagan C , Savineau JP , Loirand G , Pacaud P 
Published: October 2009

Background and purpose:  Pulmonary arterial hypertension (PAH) is associated with increased contraction and proliferation of pulmonary vascular smooth muscle cells. The anti‐diabetic drug metformin has been shown to have relaxant and anti‐proliferation properties. We thus examined the effect of metformin in PAH.Experimental approach:  Metformin effects were analysed in hypoxia‐ and monocrotaline‐induced PAH in rats. Ex vivo and in vitro analyses were performed in lungs, pulmonary artery rings and cells.Key results:  In hypoxia‐ and monocrotaline‐induced PAH, the changes in mean pulmonary arterial pressure and right heart hypertrophy were nearly normalized by metformin treatment (100 mg·kg−1·day−1). Pulmonary arterial remodelling occurring in both experimental models of PAH was also inhibited by metformin treatment. In rats with monocrotaline‐induced PAH, treatment with metformin significantly increased survival. Metformin increased endothelial nitric oxide synthase phosphorylation and decreased Rho kinase activity in pulmonary artery from rats with PAH. These effects are associated with an improvement of carbachol‐induced relaxation and reduction of phenylephrine‐induced contraction of pulmonary artery. In addition, metformin inhibited mitogen‐activated protein kinase activation and strongly reduced pulmonary arterial cell proliferation during PAH. In vitro, metformin directly inhibited pulmonary artery smooth muscle cell growth.Conclusions and implications:  Metformin protected against PAH, regardless of the initiating stimulus. This protective effect may be related to its anti‐remodelling property involving improvement of endothelial function, vasodilatory and anti‐proliferative actions. As metformin is currently prescribed to treat diabetic patients, assessment of its use as a therapy against PAH in humans should be easier.
Expanding Access to Triptans: Assessment of Clinical Outcome
Authors: Cady Roger K. , Goldstein Jerome , Silberstein Stephen , Juhász Márta , Ramsey Karen , Rodgers Anthony , Hustad Carolyn M. , Ho Tony 
Published: October 2009

Objective.— To evaluate whether access to more liberal quantities of rizatriptan improves clinical outcome in patients with episodic migraine.Background.— Currently many pharmacy benefit programs limit the number of triptan tablets/injections per month based on perceived cost savings and the belief that too‐frequent use of triptans may lead to medication overuse headache and headache chronification.Methods.— This observer‐blind, randomized, parallel‐group study enrolled 197 subjects with migraine with or without aura. Subjects completed a 3‐month baseline period to establish migraine frequency and then were randomly assigned to receive 9 (formulary limit [FL]) or 27 (clinical limit [CL]) tablets of 10 mg rizatriptan orally disintegrating tablet (ODT) per month for 3 months. The primary endpoint was change in the mean number of migraine days from the baseline to treatment period.Results.— There was no statistically significant difference between the FL and CL groups in mean number of migraine days (FL‐CL LS mean: −0.08 [−0.39, 0.23]; P = .613). Subjects in the CL group treated attacks at lower headache severity. No CL subjects were reported to have developed chronic migraine despite utilization of greater than 10 rizatriptan ODT tablets per month. Rizatriptan was generally well tolerated by both groups.Conclusion.— Providing a greater quantity of rizatriptan ODT 10 mg did not reduce the number of migraine days compared with providing 9 tablets per month for this population with episodic migraine with a frequency of 3‐8 migraines per month. Regardless of quantity provided, rizatriptan was generally well tolerated.
Adherence to Acute Migraine Medication: What Does It Mean, Why Does It Matter?
Authors: Katić Božena J. , Krause Steven J. , Tepper Stewart J. , Hu Henry X. , Bigal Marcelo E. 
Published: October 2009

(Headache 2010;50:117‐129)Proper use of medications is an important part of successfully managing migraine headache, yet migraineurs frequently switch, discontinue, or delay taking effective prescription therapies such as triptans. Medication persistence in the treatment of chronic‐episodic disorders such as migraine is not well understood. In this article we review this topic, by critically reviewing studies conducted using pharmacy claims, clinical records, survey, and patient‐reported data to explore acute medication use for migraine headache. While efficacy, cost, drug tolerability, and side effects impact whether a patient takes migraine medication, low perceived disease importance and factors related to the patient's internal decision‐making process play a strong role in the sustained use of acute medication for migraine attack. We propose a model that combines the patient's perceived severity of migraine, their beliefs regarding the safety of acute medications, and factors related to the physician–patient relationship to identify migraineurs at high risk for medication adherence problems.
Cerebellar Tonsillar Herniation After Weight Loss in a Patient With Idiopathic Intracranial Hypertension
Authors: Graber Jerome J. , Racela Rikki , Henry Katherine 
Published: October 2009

(Headache 2010;50:146‐148)Acquired cerebellar tonsillar herniation is a known complication of lumboperitoneal shunt (LPS) for any indication, including idiopathic intracranial hypertension (IIH), also known as pseudotumor cerebri.1 While the underlying pathophysiology of IIH remains unknown, increasing body mass index is a clear risk factor for the development of IIH. We describe an obese patient with IIH unresponsive to LPS who developed symptoms of intracranial hypotension and cerebellar tonsillar herniation after bariatric surgery and a 50‐kg weight loss.
Refractory status epilepticus: A prospective observational study
Authors: Novy Jan , Logroscino Giancarlo , Rossetti Andrea O. 
Published: October 2009

SummaryPurpose:  Status epilepticus (SE) that is resistant to two antiepileptic compounds is defined as refractory status epilepticus (RSE). In the few available retrospective studies, estimated RSE frequency is between 31% and 43% of patients presenting an SE episode; almost all seem to require a coma induction for treatment. We prospectively assessed RSE frequency, clinical predictors, and outcome in a tertiary clinical setting.Methods:  Over 2 years we collected 128 consecutives SE episodes (118 patients) in adults. Clinical data and their relationship to outcome (mortality and return to baseline clinical conditions) were analyzed.Results:  Twenty‐nine of 128 SE episodes (22.6%) were refractory to first‐ and second‐line antiepileptic treatments. Severity of consciousness impairment and de novo episodes were independent predictors of RSE. RSE showed a worse outcome than non‐RSE (39% vs. 11% for mortality; 21% vs. 63% for return to baseline clinical conditions). Only 12 patients with RSE (41%) required coma induction for treatment.Discussion:  This prospective study identifies clinical factors predicting the onset of SE refractoriness. RSE appears to be less frequent than previously reported in retrospective studies; furthermore, most RSE episodes were treated outside the intensive care unit (ICU). Nonetheless, we confirm that RSE is characterized by high mortality and morbidity.
An optimized voxel‐based morphometric study of gray matter changes in patients with left‐sided and right‐sided mesial temporal lobe epilepsy and hippocampal sclerosis (MTLE/HS)
Authors: Pail Martin , Brázdil Milan , Mareček Radek , Mikl Michal 
Published: October 2009

SummaryPurpose:  To determine whether changes in gray matter volume (GMV) differ according to the affected side in mesial temporal lobe epilepsy/hippocampal sclerosis (MTLE/HS) syndrome, and moreover to test the hypothesis of more pronounced structural changes in right‐sided MTLE/HS. This hypothesis (especially that the contralateral thalamus is more affected in right‐sided MTLE/HS) arose from the results of our recent study, wherein more expressed structural and functional changes were observed in a small sample of patients with right‐sided MTLE/HS (Brázdil et al., 2009).Methods:  Twenty patients with left‐sided and 20 with right‐sided MTLE/HS and 40 sex‐ and age‐matched healthy controls were included in the study. Voxel‐based morphometry (VBM) with a modulation step was applied to magnetic resonance imaging (MRI) brain images. Statistical parametric maps were used to compare structural changes between patients and controls separately for the left‐ and right‐sided MTLE/HS subgroups. We also compared the local GMV of the brain structures (insula and thalamus) between the subgroups of patients.Results:  In the subgroup with right‐sided MTLE/HS, a reduction of GMV was detected in the mesiotemporal structures and the ipsilateral thalamus (as in left‐sided MTLE/HS), but also notably in the ipsilateral insula and contralateral thalamus. A statistical analysis revealed a significantly more extensive reduction of GMV in the ipsilateral/contralateral insula and the contralateral thalamus in the subgroup with right‐sided compared to left‐sided MTLE/HS.Conclusion:  We found asymmetrical morphologic changes in patients with left‐ and right‐sided MTLE/HS syndrome (more pronounced in right‐sided MTLE/HS). These differences could be theoretically explained by different neuronal networks and pathophysiologic changes in temporolimbic structures.
Clinical significance of glutamic acid decarboxylase antibodies in patients with epilepsy
Authors: Liimatainen Suvi , Peltola Maria , Sabater Lidia , Fallah Mahdi , Kharazmi Elham , Haapala Anna‐Maija , Dastidar Prasun , Knip Mikael , Saiz Albert , Peltola Jukka 
Published: October 2009

SummaryPurpose:  Glutamic acid decarboxylase antibodies (GADAs) have been detected in patients with epilepsy, but the clinical determinants of epilepsy associated with GADA have not been defined.Methods:  We analyzed GADA with a radioimmunoassay in sera of 253 well‐characterized patients with epilepsy and 200 control subjects. The positive samples were confirmed by immunohistochemistry and western blotting (WB). Sera were screened for other autoantibodies.Results:  GADA were detected in 15 patients (5.9%) and in three control subjects (1.5%) (p = 0.026). Seven patients (2.8%) had high GADA titers [≥1,000 relative units (RUs)/ml], six of whom had temporal lobe epilepsy (TLE). All three GADA‐positive control subjects had low titers. Two of the five patients with high GADA titers and available cerebrospinal fluid (CSF) samples had intrathecal synthesis (IS) of GADA; one patient had CSF oligoclonal bands. The prevalence of increased levels of GADA tended to be higher in patients with TLE than in patients with extra‐TLE [odds ratio (OR) 1.32, 95% confidence interval (CI) 0.39–4.42; p = 0.657]. The patients with high GADA titers had significantly higher number of other autoantibodies compared to the patients with low GADA titers (p = 0.001) and the patients with normal GADA (p < 0.001).Discussion:  High GADA titers were present in a subgroup of patients; close to 90% had TLE. The immunologic profile of these patients suggests that the most probable origin of their epilepsy is autoimmune. A positive IS of GADA may be a marker of an ongoing immune response that could identify those patients in whom a trial with immunosuppressive therapy might be warranted.
Sublobar dysplasia—A clinicopathologic report after successful epilepsy surgery
Authors: Tuxhorn Ingrid , Woermann Friedrich G. , Pannek Heinz W. , Hans Volkmar H. 
Published: October 2009

SummaryWe report the clinical presentation, neuroradiologic characteristics, and detailed histopathologic findings in a unique case of drug‐resistant focal epilepsy due to sublobar dysplasia (SLD), treated successfully by resection of the malformed cortex. Histopathology with leptomeningeal and subcortical heterotopia, disturbance of cortical lamination and marked cortical and subcortical astrocytosis, but absence of balloon cells, points to a disorder of neuronal migration and organization rather than proliferation in SLD. The additional presence of a lateral proboscis and meningocele in our case as well as further associated callosal and cerebellar anomalies may suggest an etiologic unknown damage of pathways controlling the embryogenesis of craniofacial field processes.
Group‐specific regional white matter abnormality revealed in diffusion tensor imaging of medial temporal lobe epilepsy without hippocampal sclerosis
Authors: Shon Young‐Min , Kim Yeong‐In , Koo Bang‐Bon , Lee Jong‐Min , Kim Hye J. , Kim Woo J. , Ahn Kook J. , Yang Dong W. 
Published: October 2009

SummaryPurpose:  In comparison to temporal lobe epilepsy (TLE) patients with hippocampal sclerosis (TLE‐HS), TLE patients without HS (TLE‐NH) have a similar clinical course but may result in worse surgical outcome. We investigated whether the clinical features related to the lack of HS in TLE patients (TLE‐NH) can be explained by water diffusion abnormalities throughout diffusion tensor imaging (DTI) by voxel‐based analysis.Methods:  Nineteen patients with TLE‐HS (left/right TLE 12:7), 18 patients with TLE‐NH (left/right TLE 10:8), and 20 controls were included in the study. By statistical parametric mapping (SPM2), the diffusion properties specific to disease characteristics (TLE‐HS vs. TLE‐NH) were analyzed.Results:  In TLE‐HS, we found the areas of increased mean diffusivity (MD) in their ipsilateral temporal and extratemporal areas including the hippocampus, parahippocampal, and frontoparietal regions. Left TLE‐HS showed a characteristic MD increase in the ipsilateral posterior cingulum, isthmus of corpus callosum, and contralateral occipital and temporal regions, which was not observed in right TLE‐HS group. In left TLE‐NH, two regions of increased MD were observed in the ipsilateral posterior fornix (within fusiform gyrus) and posterior cingulum. Right TLE‐NH did not show any increased MD.Discussion:  In left TLE‐NH, we could find the water diffusion change along the posterior cingulum, which was quite different from the extensive abnormality from TLE‐HS. In addition, there was a lesion‐side–specific distribution (left predominant) of pathology in mesial TLE. This provides a possibility that TLE‐NH is a heterogenous or entity different from TLE‐HS.
Louis François Bravais and Jacksonian epilepsy
Authors: Eadie Mervyn 
Published: October 2009

SummaryAlthough it is known that Jacksonian epilepsy was first described by Bravais in 1827, some 40 years before Jackson began his work on the topic, little has been published on what Bravais wrote. Louis François Bravais (1801–1843) came from a French provincial family, which made a number of scientific, mainly botanical, contributions. In his Paris M.D. thesis, based on 25 instances of what he termed “hemiplegic epilepsy,” Bravais described a set of unilateral epileptic seizure phenomena, including postseizure hemiparesis, very similar to those Jackson wrote about in 1870. However, Jackson accepted that the initially unilateral convulsive phenomena could spread to involve both sides of the body, whereas Bravais believed that this was incompatible with his entity, unless the generalization was a very rare event in the sufferer. Bravais in his account refused to go beyond descriptions of phenomena, whereas Jackson reasoned from the phenomena to a new concept of epileptogenesis, and also from them deduced that there must be localized representation of function in the cerebral cortex. Although Bravais had the priority, his work went largely unnoticed until Jackson’s insights had made their impact on medical thinking.
Bilateral hippocampal stimulation for intractable temporal lobe epilepsy: Impact on seizures and memory
Authors: McLachlan Richard S. , Pigott Susan , Tellez‐Zenteno Jose F. , Wiebe Samuel , Parrent Andrew 
Published: October 2009

SummaryThe effect of continuous electrical stimulation of the hippocampus bilaterally on seizures and memory was assessed in two subjects with seizures from both mesial temporal lobes who were not candidates for resective epilepsy surgery. A double blind, randomized, controlled, cross‐over trial design was utilized. Two electrodes with four contacts each were implanted along the axis of the hippocampus bilaterally. Simultaneous stimulation of all electrodes contacts was either on or off during each 3‐month interval. Seizure frequency decreased by 33% in the two patients during stimulation and remained lower by 25% for the 3 months after stimulation was turned off before returning to baseline (p < 0.01). No consistent change in objective or subjective measures of memory occurred. No other adverse effects occurred. Seizure frequency is reduced both during and for a period after bilateral hippocampal stimulation, but the overall impact in this study is not as robust as has been previously reported.
A comparison of midazolam nasal spray and diazepam rectal solution for the residential treatment of seizure exacerbations
Authors: De Haan Gerrit‐Jan , Van Der Geest Peter , Doelman Gerard , Bertram Edward , Edelbroek Peter 
Published: October 2009

SummaryRectal diazepam is established as a standard rescue or emergency treatment for seizure or status epilepticus; however, the rectal route of administration has not been universally accepted. To determine if an alternative route of administration of a benzodiazepine was equally effective, we compared a novel midazolam HCl concentrated nasal spray (MDZ‐n) with diazepam rectal solution (DZP‐r) in the treatment of prolonged seizures in a residential epilepsy center. In 21 adult patients with medically refractory epilepsy, 124 seizure‐exacerbations were treated by their caregivers, alternatively with 10 mg DZP‐r and 10 mg concentrated MDZ‐n, two or three treatments with each medication for each patient. No difference was demonstrated in efficacy or time to effect between the two drugs. Common treatment emerging adverse effects were drowsiness for both drugs in more than 50% of the administrations, and short‐lasting local irritation after 29% of MDZ‐n. No severe adverse events occurred. The nasal spray was preferred to the rectal solution by 16 of 21 caregivers and patients conjointly. MDZ‐n was equal to DZP‐r with respect to efficacy and side effects in the suppression of seizure exacerbations. The majority of patients and caregivers preferred the nasal spray over the rectal formulation.
The teratogenic risk of antiepileptic drug polytherapy
Authors: Vajda Frank J. E. , Hitchcock Alison A. , Graham Janet , O’Brien Terence J. , Lander Cecilie M. , Eadie Mervyn J. 
Published: October 2009

SummaryPurpose:  To compare the risks of fetal malformation during pregnancy associated with antiepileptic drug (AED) polytherapy and monotherapy.Methods:  Statistical analysis of malformation rate and antiepileptic drug exposure data from the Australian Register of Antiepileptic Drugs in Pregnancy, and from the literature.Results:  The calculated relative risk (RR) value for AED polytherapy compared with monotherapy was below 1.0 in only 3 of 14 literature publications. In the register, at 1 year postnatally there were fetal malformations in 5.32% of 282 AED polytherapy pregnancies, and in 7.84% of 791 AED monotherapy pregnancies, an RR of 0.68 [95% confidence interval (CI) 0.39–1.17). For pregnancies exposed to valproate, the RR of fetal malformation (0.39, 95% CI 0.20–0.89) was lower in polytherapy (7.26%) than in monotherapy (17.9%); the difference did not depend on valproate dosage. The RR values for fetal malformation were not significantly different for AED polytherapy and monotherapy when valproate was not involved. Logistic regression suggested that coadministration of lamotrigine may have reduced the malformation risk from valproate.Discussion:  The fetal hazard of AED polytherapy relative to monotherapy may depend more on the degree of exposure to valproate than on the fact of polytherapy per se. Coadministration with lamotrigine may lower the fetal risk of valproate therapy.