bluuebunny/crossref_metadata_2025_split huggingface dataset:
Emergency room visit: a red‐flag indicator for poor diabetes care
Authors: Stern Z. , Calderon‐Margalit R. , Mazar M. , Brezis M. , Tirosh A. 
Published: August 2009

AbstractAim  To determine the association between emergency room (ER) admission and quality of diabetes care in the community.Methods  In a nested case–control study of patients with Type 2 diabetes mellitus (DM) within a large health maintenance organization (HMO) in Israel, 919 patients who were admitted to one of West Jerusalem’s ERs between 1 May and 30 June 2004 were compared with 1952 control subjects not admitted. Data on study covariates were retrieved from the HMO’s computerized database and a subset of the study population was interviewed. Logistic regressions were conducted to estimate the odds ratios of being admitted according to different measures of quality of care, controlling for socio‐demographic variables, co‐morbidities and type of DM treatment.Results  The main indices of quality of primary care that were inversely associated with visiting an ER during the study period included performance of a cholesterol test in the year prior to the index date [adjusted odds ratio (OR) 0.23, 95% confidence interval (CI) 0.19–0.29, P < 0.001], performance of glycated haemoglobin test (OR 0.26, 95% CI 0.24–0.29, P < 0.001), visiting an ophthalmologist (OR 0.47, 95% CI 0.32–0.68, P = 0.001), and recommendations to stop smoking (OR 0.10, 95% CI 0.05–0.21, P < 0.001).Conclusions  Admission to the ER can be used as an indicator for poor quality of diabetes care. There is an association between ER admission and poor quality of diabetes care.
Conservative management of diabetic forefoot ulceration complicated by underlying osteomyelitis: the benefits of magnetic resonance imaging
Authors: Valabhji J. , Oliver N. , Samarasinghe D. , Mali T. , Gibbs R. G. J. , Gedroyc W. M. W. 
Published: August 2009

AbstractAims  To assess efficacy of conservative management of neuropathic forefoot ulcers with underlying osteomyelitis in subjects with diabetes when magnetic resonance imaging (MRI) is used to confirm or establish diagnosis and to guide antibiotic duration.Methods  A retrospective cohort study over 6 years assessing rates of ulcer healing, relapse and amputation. Antibiotics were continued for 3‐month cycles with interval MRI: if the lesion had healed and bone signal change resolved or improved, antibiotics were discontinued; if the lesion had not healed or there was no difference in bone signal change, antibiotics were continued for a further 3‐month cycle; clinical or radiological deterioration resulted in endoluminal or open vascular surgical intervention where appropriate, or digital or more proximal amputation.Results  There were 53 episodes in 47 subjects (mean ± sd age 62 ± 13 years, duration of diabetes 19 ± 13 years, glycated haemoglobin 8.4 ± 1.6%; six with Type 1 diabetes and seven with end‐stage renal failure). Successful healing without relapse was achieved in 40 episodes (75%) [median (range) duration of antibiotics 6 (3–12) months and follow‐up post‐cessation of antibiotics 15 (3–58) months]. Relapse occurred in six episodes (13%) at 31 (2–38) months post‐cessation of antibiotics. There were one major (2%) and eight minor (15%) amputations. Five subjects have died (11%), all without foot ulcers.Conclusions  High rates of healing and low rates of amputation were achieved. The use of MRI was associated with long courses of antibiotics, but particularly low relapse rate.
Global Imbalances: The Role of Emerging Asia
Authors: Cova Pietro , Pisani Massimiliano , Rebucci Alessandro 
Published: August 2009

AbstractThis paper investigates the role played by emerging Asia in the emergence and evolution of the global trade imbalances. Based on simulations in a general‐equilibrium model of the world economy, we find that a productivity slowdown in the nontradable sector of these economies in the second half of the 1990s fits regional macroeconomic developments relatively well, but has limited spillover effect to the United States trade balance. In contrast, an increase in the desired level of emerging Asia net foreign assets starting in 2001 not only fits regional developments relatively well, but also has a significant spillover effect to the United States.
Evidence of shared genetic risk factors for migraine and rolandic epilepsy
Authors: Clarke Tara , Baskurt Zeynep , Strug Lisa J. , Pal Deb K. 
Published: August 2009

SummaryPurpose:  Evidence for a specific association between migraine and rolandic epilepsy (RE) has been conflicting. Children with migraine frequently have electroencephalographic (EEG) abnormalities, including rolandic discharges, and approximately 50% of siblings of patients with RE exhibit rolandic discharges. We assessed migraine risk in RE probands and their siblings.Methods:  We used cohort and reconstructed cohort designs to respectively assess the relative risk of migraine in 72 children with RE and their 88 siblings using International Classification of Headache Disorders (ICHD‐2) criteria. Incidences were compared in 150 age and geographically matched nonepilepsy probands and their 188 siblings. We used a Cox proportional hazards model, using age as the time base, adjusting hazard ratios (HRs) for sex in the proband analysis, and for sex and proband migraine status in the sibling analysis.Results:  Prevalence of migraine in RE probands was 15% versus 7% in nonepilepsy probands, and in siblings of RE probands prevalence was 14% versus 4% in nonepilepsy siblings. The sex‐adjusted HR of migraine for an RE proband was 2.46 [95% confidence interval (CI) 1.06–5.70]. The adjusted HR of having ≥1 sibling with migraine in an RE family was 3.35 (95% CI 1.20–9.33), whereas the HR of any one sibling of a RE proband was 2.86 (95% CI 1.10–7.43).Discussion:  Migraine is strongly comorbid in RE and independently clusters in their siblings. These results suggest shared susceptibility to migraine and RE that is not directly mediated by epileptic seizures. Susceptibility gene variants for RE may be tested as risk factors for migraine.
Evaluation of stereoselective anticonvulsant, teratogenic, and pharmacokinetic profile of valnoctylurea (capuride): A chiral stereoisomer of valproic acid urea derivative
Authors: Shimshoni Jakob A. , Yagen Boris , Wlodarczyk Bogdan , Finnell Richard H. , Schurig Volker , Bialer Meir 
Published: August 2009

SummaryPurpose: The purpose of this study was to evaluate the stereoselective anticonvulsant activity, neurotoxicity, pharmacokinetics, and teratogenic potential of two stereoisomers of valnoctylurea (VCU), a central nervous system (CNS)–active urea derivative of valnoctic acid, which is a constitutional isomer of valproic acid (VPA).Methods: VCU stereoisomers (2S,3S)‐VCU and (2R,3S)‐VCU were synthesized. Their anticonvulsant activity was determined and compared to VPA and racemic‐VCU in rats utilizing the maximal electroshock seizure (MES) and the subcutaneous pentylenetetrazole (scMet) tests. Neurotoxicity was determined in rats using the positional sense test, muscle tone test, and gait and stance test. The induction of neural tube defects (NTDs) by VCU stereoisomers was evaluated in a mouse strain highly susceptible to VPA‐induced teratogenicity. The pharmacokinetics of VCU was studied in a stereoselective manner following intraperitoneal (i.p.) administration to rats.Results: (2S,3S)‐VCU and (2R,3S)‐VCU median effective dose ED50values were 29 mg/kg [95% confidence interval (CI) = 8–60 mg/kg] and 42 mg/kg (95% CI = 36–51 mg/kg) (MES) and 22 mg/kg (95% CI = 13–51 mg/kg) and 12 mg/kg (95%CI = 7–21 mg/kg) (scMet), respectively. (2S,3S)‐VCU was more potent and had a wider safety margin (p < 0.05), defined as the protective index (PI = TD50/ED50), at both the MES (PI > 17) and scMet (PI > 23) tests than racemic‐VCU or (R,S)‐VCU (PI = 2.8 and 9.9, respectively). VCU stereoisomers caused NTDs at doses >4 times that of their anticonvulsant ED50values. At a dose of 112 mg/kg, (2R,3S)‐VCU was nonteratogenic and less embryotoxic than its stereoisomer (2S,3S)‐VCU. No stereoselective pharmacokinetics was observed following intraperitoneal dosing of racemic‐VCU to rats. VCU was mainly eliminated by metabolism with a half‐life of 2 h.Conclusions: VCU anticonvulsant activity and wide PI values make it a potential candidate for development as a new, potent antiepileptic drug (AED).
Seizures increase cell proliferation in the dentate gyrus by shortening progenitor cell‐cycle length
Authors: Varodayan Florence P. , Zhu Xin‐Jian , Cui Xiao‐Nan , Porter Brenda E. 
Published: August 2009

SummaryPurpose:  A prolonged seizure, status epileptics (SE), is a potent stimulus for increased neurogenesis in the dentate gyrus of the hippocampus. Molecular mechanisms that regulate normal and pathologic cell birth in the dentate gyrus are poorly understood.Methods:  Lithium–pilocarpine was used to induce SE in immature postnatal day 20 rats. Newborn cells in the dentate were labeled with bromo‐deoxyuridine to determine a time‐course of cell proliferation, and measure cell‐cycle length. In addition, we studied expression by Western blot and immunohistochemistry of two known inhibitors of G1–S cell‐cycle progression P27/Kip1 and P15/Ink4b following SE.Results:  Cell proliferation in the dentate gyrus increases starting 2 h after SE and is sustained for 40 days. Increased cell proliferation following SE is associated with a shortened dentate gyrus progenitor’s cell cycle, 15 h in control to 12 h in the SE animals. To identify molecules responsible for the shortened progenitor cell cycle we studied inhibitors of cell‐cycle progression P27/Kip1, and P15/Ink4b. We find decreased phosphorylation at P27/Kip1 Serine 10 and Threonine 187 following SE. Although total P27/Kip1 and P15/Ink4b levels were not altered after SE, P27/Kip1 immunoreactivity was minimal in newborn but increased with maturation of the dentate granule neurons.Discussion:  The sustained increase in dentate gyrus cell proliferation following SE provides a large pool of immature dentate granule cells prior to development of spontaneous seizures. A decrease in cell‐cycle length of dentate gyrus progenitors is at least partially responsible for increased numbers of newborn cells following SE.
Bitemporal form of partial reading epilepsy: Further evidence for an idiopathic localization‐related syndrome
Authors: Maillard Louis , Vignal Jean‐Pierre , Raffo Emmanuel , Vespignani Hervé 
Published: August 2009

SummaryIdiopathic partial reading epilepsy (RE) is a rare syndrome. We report the clinical and electroencephalographic characteristics of two right‐handed patients with the following: reading‐induced independent bilateral temporal lobe seizures, accompanied by alexia in left (dominant) sided seizures recorded on video‐EEG (electroencephalography); subclinical activation over left posterior temporal and occipital electrodes during reading; no spontaneous seizure and no other trigger than reading; onset in adolescence; and history of varying resistance to treatment. Bilateral independent temporal lobe reflex seizures are part of the clinical spectrum of RE. It may result from hyperexcitability of bilateral cortical networks involved in the early steps of the reading process.
A novel mouse model for sudden unexpected death in epilepsy (SUDEP): Role of impaired adenosine clearance
Authors: Shen Hai‐Ying , Li Tianfu , Boison Detlev 
Published: August 2009

SummarySudden unexpected death in epilepsy (SUDEP) is a significant cause of mortality in people with epilepsy. Two postulated causes for SUDEP, cardiac and respiratory depression, can both be explained by overstimulation of adenosine receptors. We hypothesized that SUDEP is a consequence of a surge in adenosine as a result of prolonged seizures combined with deficient adenosine clearance; consequently, blockade of adenosine receptors should prevent SUDEP. Here we induced impaired adenosine clearance in adult mice by pharmacologic inhibition of the adenosine‐removing enzymes, adenosine kinase and deaminase. Combination of impaired adenosine clearance with kainic acid–induced seizures triggered sudden death in all animals. Most importantly, the adenosine receptor antagonist caffeine, when given after seizure onset, increased survival from 23.75 ± 1.35 min to 54.86 ± 6.59 min (p < 0.01). Our data indicate that SUDEP is due to overactivation of adenosine receptors and that caffeine treatment after seizure onset might be beneficial.
Reevaluating the mechanisms of focal ictogenesis: The role of low‐voltage fast activity
Authors: De Curtis Marco , Gnatkovsky Vadym 
Published: August 2009

SummaryThe mechanisms that control the transition into a focal seizure are still uncertain. The introduction of presurgical intracranial recordings to localize the epileptogenic zone in patients with drug‐resistant focal epilepsies opened a new window to the interpretation of seizure generation (ictogenesis). One of the most frequent focal patterns observed with intracranial electrodes at seizure onset is characterized by low‐voltage fast activity in the beta‐gamma range that may or may not be preceded by changes of ongoing interictal activities. In the present commentary, the mechanisms of generation of focal seizures are reconsidered, focusing on low‐voltage fast activity patterns. Experimental findings on models of temporal lobe seizures support the view that the low‐voltage fast activity observed at seizure onset is associated with reinforcement and synchronization of inhibitory networks. A minor role for the initiation of the ictal pattern is played by principal neurons that are progressively recruited with a delay, when inhibition declines and synchronous high‐voltage discharges ensue. The transition from inhibition into excitatory recruitment is probably mediated by local increase in potassium concentration associated with synchronized interneuronal firing. These findings challenge the classical theory that proposes an increment of excitation and/or a reduction of inhibition as a cause for the transition to seizure in focal epilepsies. A new definition of ictogenesis mechanisms, as herewith hypothesized, might possibly help to develop new therapeutic strategies for focal epilepsies.
Protective effects of naloxone in two‐hit seizure model
Authors: Yang Lu , Li Fuhai , Ge Wei , Mi Changrui , Wang Rong , Sun Ruopeng 
Published: August 2009

SummaryPurpose: Early life status epilepticus (SE) could enhance the vulnerability of the immature brain to a second SE in adulthood (two‐hit seizure model). Naloxone has been proved to possess inflammation inhibitory effects in nervous system. This study was designed to evaluate the dose‐dependent protective effects of naloxone in kainic acid (KA)–induced two‐hit seizure model.Methods: After KA‐induced SE at postnatal day 15 (P15), Sprague‐Dawley rats were infused with either saline or different doses (1.92, 3.84, 5.76, and 7.68 mg/kg) of naloxone continuously for 12 h. De novo synthesis of cytokines (interleukin‐1β [IL‐1β], S100B) was assessed by real‐time polymerase chain reaction (PCR) and enzyme‐linked immunosorbent assay (ELISA) at 12 h after P15 SE. Glial activation states were analyzed by western blotting of glial markers (glial fibrillary acidic protein [GFAP], S100B, Iba1) both at 12 h after P15 SE and at P45. After a second SE at P45, cognitive deteriorations were evaluated by Morris water tests and neuron injuries were evaluated by TdT‐mediated dUTP nick end labeling (TUNEL) assays.Results: Naloxone reduced IL‐1β synthesis and microglial activation most potently at a dose of 3.84 mg/kg. Attenuation of S100B synthesis and astrocyte activation were achieved most dramatically by naloxone at a dose of 5.76 mg/kg, which is equal to the most powerful dose in ameliorating cognitive injuries and neuron apoptosis after second SE.Conclusions: Naloxone treatment immediately after early life SE could dose‐dependently reduce cytokine production, glial activation, and further lower the vulnerability of immature brains to a second hit in adulthood.
Incidence of newly diagnosed epileptic seizures in a French South Indian Ocean Island, La Réunion (EPIREUN)
Authors: Mignard Claude , Tchalla Edem , Marin Benoît , Tabailloux Emmanuel , Mignard Didier , Jallon Pierre , Preux Pierre‐Marie 
Published: August 2009

SummaryPurpose:  To assess the incidence of newly diagnosed epileptic seizures in the population of La Réunion.Methods:  From July 1, 2004 to June 30, 2005, we conducted a prospective, observational, and multicenter epidemiologic study to identify patients with newly diagnosed epileptic seizures. Febrile and neonatal seizures were excluded.Results:  Seven hundred sixty‐six patients were included. The standardized (2000 U.S. population) incidence rate of all suspected cases of newly diagnosed (provoked and unprovoked) epileptic seizures was 115.4/100.000 person‐years [95% confidence interval (CI) 106.7–124.0]. We observed a bimodal distribution: The crude incidence was 99.5/100,000 in the group aged 0–14 years and 330.8/100,000 in those older than 65 years. One hundred thirty‐five cases were classified as provoked seizures (17.6%; incidence 17.7/100,000). Alcohol consumption, cranial trauma, and cerebrovascular disease were the most frequent causes (27.4%, 11.1%, and 10.4%, respectively). Six hundred twenty cases were classified as unprovoked seizures (single and recurrent) (80.9%; incidence, 81.2/100,000). Two hundred sixty cases of seizures were due to stable neurologic conditions (incidence, 34.1/100,000) and the most common causes were cerebrovascular disease (46.2%), alcoholism (20.4%), and cranial trauma (5.4%). Evolutive neurologic conditions contributed to 23 cases (incidence, 3.0/100,000). Lastly, unprovoked seizures with unknown etiology were 337 (incidence, 44.2/100,000).Conclusions:  The global incidence rate of newly diagnosed epileptic seizures in La Réunion was clearly higher than those observed in industrialized countries and similar to those observed in developing countries. The major risk factors were represented by cerebrovascular disease, alcohol consumption, and cranial trauma. Surprisingly, there were few infections.
Optical suppression of experimental seizures in rat brain slices
Authors: Yang Xiao‐Feng , Schmidt Brigitte F. , Rode Daniel L. , Rothman Steven M. 
Published: August 2009

SummaryPurpose:  To determine if a small ultraviolet emitting diode (UV LED) could release sufficient γ‐aminobutyric acid (GABA) from a caged precursor to suppress paroxysmal activity in rat brain slices.Methods:  Electrophysiologic recordings were obtained from rat brain slices bathed with caged GABA: 4‐[[(2H‐benzopyran‐2‐one‐7‐amino‐4‐methoxy)carbonyl]amino]butanoic acid (BC204), at concentrations between 3 and 30 μm. Seizure‐like activity was induced by perfusing slices with extracellular medium lacking magnesium and containing 4‐aminopyridine (4‐AP; 100 μm). A small, high‐power UV LED was used to uncage BC204 and determine whether an increase in ambient GABA could alter normal or paroxysmal activity in the slice.Results:  UV LED illumination, in the absence of BC204, had no effect on CA1 population spikes or seizure‐like activity. The light did induce a small temperature elevation (<0.15°C) over the current intensities and exposure durations used in these experiments. In the presence of BC204, UV light decreased the CA1 population spike and seizure‐like activity. The BC204 effect can be best accounted for by release of GABA: The reduction of population spikes and seizure‐like activity was blocked by the GABA antagonist picrotoxin, and BC204 illumination produced a membrane polarization that reversed at the expected potential for GABAA receptors.Discussion:  These experiments establish that illumination of a low concentration of caged GABA with a tiny UV LED can release sufficient GABA to attenuate seizure‐like activity in brain slices. Because our seizure model is very severe, it is probable that this technique would have a robust effect in human focal epilepsy.
Balance impairment in chronic antiepileptic drug users: A twin and sibling study
Authors: Petty Sandra J. , Hill Keith D. , Haber Natalie E. , Paton Lynda M. , Lawrence Kate M. , Berkovic Samuel F. , Seibel Markus J. , O’Brien Terence J. , Wark John D. 
Published: August 2009

SummaryPurpose:  Patients taking antiepileptic drugs (AEDs) have an increased incidence of fractures. This study investigated chronic AED use and physical contributors to falls risk using an AED‐discordant, twin and sibling matched‐pair approach, and assessed clinically relevant subgroups: AED polytherapy; longer‐duration AED; and falls history.Methods:  Twenty‐nine same‐sex (mean age 44.9 years, 59% female), ambulatory, community‐dwelling twin and sibling pairs, discordant for AED exposure (and AED‐indication), were recruited. Validated clinical and laboratory tests of strength, gait, and balance were performed. Relevant AED levels, and fasting serum samples for 25‐hydroxyvitamin D (25OHD), 1,25‐dihydroxyvitamin D [1,25(OH)2D], and immunoreactive parathyroid hormone (iPTH) levels were taken.Results:  There were significant mean within‐pair differences in tests of static and dynamic balance, with the AED user having poorer balance function than the AED nonuser. No difference was seen in lower limb strength or gait measures. Increased duration of AED therapy and AED polytherapy were independent predictors of increased sway. No significant within‐pair differences were seen in fasting serum levels of 1,25(OH)2D, 25OHD and iPTH after Bonferroni correction.Discussion:  Balance performance is impaired in AED users compared to their matched nonuser siblings. Pairs where the AED users took AED polytherapy, or had a longer duration of AED use, had more impaired balance performance. These balance deficits may contribute to the increased rate of fractures in this population.
Parkinsonism induced by VNS in a child with double‐cortex syndrome
Authors: Cukiert Arthur , Mariani Pedro Paulo , Burattini Jose Augusto , Cukiert Cristine Mella , Forster Cassio , Baise Carla , Argentoni‐Baldochi Meire , Mello Valeria 
Published: August 2009

SummaryWe describe a child with epilepsy associated with double‐cortex syndrome in whom vagus nerve stimulation (VNS) generated parkinsonian symptoms. A 13‐year‐old girl presented with refractory secondary generalized epilepsy from the age of 6 years and mental retardation. Her electroencephalography (EEG) showed diffuse polyspike and wave discharges. Magnetic resonance imaging (MRI) showed double‐cortex syndrome. She was submitted to extended callosal section at the age of 10 years, which yielded 50% seizure frequency reduction. She was submitted to VNS by the age of 12 years. As stimulation intensity was increased, there was appearance of extrapyramidal symptoms: She developed bilateral tremor and rigidity, and gait and postural disturbance. All symptoms disappeared 7–10 days after VNS was turned off. Several attempts to reactivate VNS led to the same results. During the periods when VNS was on she presented with marked seizure frequency reduction. This is the first report of a clinically evident direct effect of VNS on the basal ganglia.