bluuebunny/crossref_metadata_2025_split huggingface dataset:
Benign Myoclonic Epilepsy in Infants: Electroclinical Features and Long‐term Follow‐up of 34 Patients
Authors: Auvin Stéphane , Pandit Florence , De Bellecize Jullita , Badinand Nicole , Isnard Hervé , Motte Jacques , Villeneuve Nathalie , Lamblin Marie‐Dominique , Vallée Louis ,   Epilepsy Study Group of the French Pediatric Neurology Society
Published: February 2006

Summary: Purpose:Benign myoclonic epilepsy in infants (BMEI) is a rare epileptic syndrome characterized only by generalized myoclonic seizures (MSs) in normal children during the first 2 years. Our aim was to assess the electroclinical features and the follow‐up of this syndrome.Methods:BMEI was confirmed by electroencephalogram (EEG) in four neuropediatric units in France between 1981 and 2002. Clinical and electroencephalographic findings at diagnosis and during the follow‐up were collected. The Vineland scale or Wechsler scale or both were used to perform neuropsychological evaluations.Results:We report 34 patients with BMEI characterized by MSs occurring many times a day. The ictal EEG showed a generalized discharge of polyspikes, polyspikes‐and‐waves, or spikes‐and‐waves. The interictal EEG was usually normal. A family history of febrile seizures (FSs) or epilepsy was noted in six patients. A history of FSs was noted in 11 patients. Eleven patients had reflex MSs. Monotherapy with valproic acid was effective in 23 of 30 treated patients. The onset of epilepsy was known in all patients. Four patients had seizures after the initial symptoms. Juvenile myoclonic epilepsy developed in two patients, and cryptogenic partial epilepsy in another. Neuropsychological outcome was evaluated in 20 patients (10 with Wechsler scales and 17 with the Vineland scale). Cognitive functions were normal in 17 patients, whereas developmental delay was observed in three others.Conclusions:BMEI is clinically characterized by myoclonic seizures involving the upper part of the body, occurring many times a day. The ictal EEG showed a generalized discharge of polyspikes, polyspikes‐and‐waves, or spikes‐and‐waves. The interictal EEG was usually normal. Reflex MSs were frequently observed, suggesting that two distinctive syndromes are not necessary. BMEI may be followed by juvenile myoclonic epilepsy. Despite a generally favorable neuropsychological outcome, mental retardation can be observed more frequently than in the general population.
Postsurgical Outcome in Pediatric Patients with Epilepsy: A Comparison of Patients with Intellectual Disabilities, Subaverage Intelligence, and Average‐Range Intelligence
Authors: Gleissner Ulrike , Clusmann Hans , Sassen Robert , Elger Christian E. , Helmstaedter Christoph 
Published: February 2006

Summary: Purpose:Intellectual disabilities are often associated with bilateral or diffuse morphologic brain damage. The chances of becoming seizure free after focal surgery are therefore considered to be worse in patients with intellectual disabilities. The risk of postoperative cognitive deficits could increase because diffuse brain damage lowers the patient's ability to compensate for surgically induced deficits. Several studies in adult patients have indicated that IQ alone is not a good predictor of postoperative cognitive and seizure outcome. Our study evaluated this subject in children and adolescents.Methods:Pediatric patients with intellectual disabilities (IQ ≤ 70), subaverage intelligence (IQ between 71 and 85), or average‐range intelligence (IQ > 85) were matched according to several clinical and etiologic criteria to determine the influence of IQ (N = 66).Results:No dependency of seizure outcome, postoperative cognitive development, and behavioral outcome on the IQ level was found. All groups slightly improved in attention while memory functions tended to decrease and executive functions were stable. School placement remained unchanged for the majority of patients. Between 67 and 78% were seizure free 1 year after surgery (Engel outcome class I).Conclusions:IQ alone is not a good predictor of postoperative outcome in pediatric patients with epilepsy. As with patients of average‐range intelligence, the decision to operate on patients with a low level of intelligence should depend on the results of the presurgical diagnostics. If the results of the neuropsychological examination indicate diffuse functional impairment, this should not hinder further steps, if all other findings are consistent.
A Modified Atkins Diet Is Effective for the Treatment of Intractable Pediatric Epilepsy
Authors: Kossoff Eric H. , McGrogan Jane R. , Bluml Renee M. , Pillas Diana J. , Rubenstein James E. , Vining Eileen P. 
Published: February 2006

Summary:  Purpose: The Atkins diet may induce ketosis as does the ketogenic diet, without restrictions on calories, fluids, protein, or need for an inpatient fast and admission. Our objective was to evaluate the efficacy and tolerability of a modified Atkins diet for intractable childhood epilepsy. Methods: Twenty children were treated prospectively in a hospital‐based ambulatory clinic from September 2003 to May 2005. Children aged 3–18 years, with at least three seizures per week, who had been treated with at least two anticonvulsants, were enrolled and received the diet over a 6‐month period. Carbohydrates were initially limited to 10 g/day, and fats were encouraged. Parents measured urinary ketones semiweekly and recorded seizures daily. All children received vitamin and calcium supplementation. Results: In all children, at least moderate urinary ketosis developed within 4 days (mean, 1.9). Sixteen (80%) completed the 6‐month study; 14 chose to remain on the diet afterward. At 6 months, 13 (65%) had >50% improvement, and seven (35%) had >90% improvement (four were seizure free). Mean seizure frequency after 6 months was 40 per week (p = 0.005). Over a 6‐month period, mean serum blood urea nitrogen increased from 12 to 17 mg/dl (p = 0.01); creatinine was unchanged. Cholesterol increased from 192 to 221 mg/dl, (p = 0.06). Weight did not change significantly (34.0–33.7 kg); only six children lost weight. A stable body mass index over time correlated with >90% improvement (p = 0.004). Conclusions: A modified Atkins diet is an effective and well‐tolerated therapy for intractable pediatric epilepsy.
The Outcome of Children with Intractable Seizures: A 3‐ to 6‐Year Follow‐up of 67 Children Who Remained on the Ketogenic Diet Less Than One Year
Authors: Marsh Elisabeth B. , Freeman John M. , Kossoff Eric H. , Vining Eileen P. G. , Rubenstein James E. , Pyzik Paula L. , Hemingway Cheryl 
Published: February 2006

Summary: Purpose:To determine the long‐term outcome of children with difficult‐to‐control seizures who remained on the ketogenic diet for <1 year.Methods:Between 1994 and 1996, 150 children with epilepsy, refractory to at least two medications, initiated the ketogenic diet according to the Hopkins protocol. Three to six years after diet initiation, all the families were contacted by telephone or questionnaire to assess their child's current seizure status, medications, and therapies.Results:Sixty‐seven children discontinued the diet within 1 year of initiation. Follow‐up data were available for 54 of these children. Ten subsequently had surgery, and three underwent VNS implantation. These operated‐on children were significantly more likely to be >50% controlled at follow‐up than were those managed with medications alone (p < 0.05). A statistically significant difference in long‐term outcome was noted between those who responded while on the diet, even if they discontinued it before 1 year, and those who did not (p < 0.05), but no statistical correlation was found between length of time that they had remained on the diet and long‐term prognosis.Conclusions:Almost half of the children who discontinued the diet during the first year had a decrease in seizures when assessed 3–6 years later. Twenty‐two percent of these had become seizure free without surgery. We were unable to ascertain whether this may have been due to new medications. Those who saw some improvement while on the diet were more likely to have a favorable long‐term outcome. Resective surgery, in children who were candidates, or vagal nerve stimulation (VNS) implantation, was more likely to result in significant seizure improvement than was management with medications alone. Whether or not the diet was effective, most families did not regret trying it and would recommend it to others.
Lack of Association between a GABAB Receptor 1 Gene Polymorphism and Temporal Lobe Epilepsy
Authors: Stogmann Elisabeth , Zimprich Alexander , Baumgartner Christoph , Gleiss Andreas , Zimprich Fritz 
Published: February 2006

Summary:  Purpose: Recently a coding nonsynonymous single‐nucleotide polymorphism (SNP; G1465A) in the GABBR1 gene was reported to be associated with the incidence and severity of temporal lobe epilepsy (TLE). To clarify the role of this polymorphism in TLE, we attempted to replicate this study. Methods: We genotyped 188 unrelated patients with TLE (110 women, 78 men) and 259 controls of middle European descent by a restriction‐length polymerase chain reaction (PCR) assay. Results: Only two (0.5%) patients and none of the controls exhibited the heterozygous A/G genotype, which was previously reported to be overrepresented among patients as compared with controls. Conclusions: Although our study was sufficiently powered, we could not replicate the original association. Potential reasons for this failure could lie in subtle genetic differences between the studied populations or differences in the TLE phenotypes.
Linking Generalized Spike‐and‐Wave Discharges and Resting State Brain Activity by Using EEG/fMRI in a Patient with Absence Seizures
Authors: Laufs Helmut , Lengler Ulrike , Hamandi Khalid , Kleinschmidt Andreas , Krakow Karsten 
Published: February 2006

Summary:  Purpose: To illustrate a functional interpretation of blood oxygen level–dependent (BOLD) signal changes associated with generalized spike‐and‐wave discharges in patients with absence seizures and to demonstrate the reproducibility of these findings in one case. Methods: In a 47 year‐old patient with frequent absence seizures, BOLD signal changes during generalized spike‐and‐wave discharges (GSWD) were mapped by using simultaneous and continuous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) at 1.5 T and 6 months later at 3 T. GSWDs were modeled as individual events and as blocks. Results: The patient studied exhibited frequent generalized spike–wave activity with temporal properties ideal for study with EEG/fMRI. Highly reproducible GSWD‐associated fMRI signal decreases (deactivations) were seen in bilateral frontal and temporoparietal cortices and the precuneus, in addition to activations in occipital cortex and, at 3 T, the posterior thalamus. Conclusions: The GSWD‐associated changes seen here involve cortical regions that have been shown to be more active at conscious rest compared with sleep and with various types of extroverted perception and action. These regions have been proposed to constitute the core of a functional “default mode” system. We propose that the findings of deactivation of this distributed brain system during GSWDs mirrors the clinical manifestation of GSWDs (i.e., absence seizures). Furthermore, we suggest that these deactivations may reflect the functional consequences of GSWDs on physiologic brain activity at rest rather than direct hemodynamic correlates of epileptic discharges.
Structural Constraints for Alcohol‐Stimulated Ca2+Release in Neural Crest, and Dual Agonist/Antagonist Properties ofn‐Octanol
Authors: Garic‐Stankovic Ana , Hernandez Marcos , Flentke George R. , Smith Susan M. 
Published: February 2006

Background:Prenatal ethanol exposure is a leading cause of mental retardation. Alcohol damages susceptible neuronal populations through its alteration of signaling pathways that direct cellular activity and survival. In early neural crest cells, ethanol elicits an intracellular Ca2+transient that is necessary and sufficient to cause apoptosis. We tested the hypothesis that ethanol's activity represents a saturable and selective effect of alcohols upon this pathway.Methods:Fura‐2–loaded chick embryos, at the 3‐somite stage, were exposed ton‐alcohols ranging in size from ethanol (C2) to decanol (C10). Thereafter, Ca2+mobilization was measured using Fura‐2 and ratiometric imaging. Apoptosis was assessed using acridine orange uptake.Results:Ethanol caused the dose‐dependent mobilization of intracellular Ca2+within neural crest populations, with an EC50of 52.0 mM.n‐Alcohols displayed increasing potency for Ca2+mobilization through pentanol. Hexanol and heptanol were inactive. Unexpectedly, micromolarn‐octanol concentrations triggered significant Ca2+release and apoptosis in a G‐protein–dependent manner. Decanol was inactive. Coaddition of either octanol or decanol antagonized the ability of ethanol to stimulate Ca2+release.Conclusions:The selective, saturable effect ofn‐alcohols upon Ca2+mobilization in neural crest is consistent with a hypothesis that ethanol stimulates these signals through specific interaction with one or more alcohol‐binding sites on a target protein. Octanol may overcome structural constraints imposed upon C6 and C7 in interacting with this protein target; alternatively, it may interact through a unique binding site.
Effects of Amino Acid Substitutions in Transmembrane Domains of the NR1 Subunit on the Ethanol Inhibition of RecombinantN‐Methyl‐d‐aspartate Receptors
Authors: Thetford Smothers C. , Woodward John J. 
Published: February 2006

Background:TheN‐methyl‐d‐aspartate (NMDA) subtype of glutamate receptor is involved in a variety of processes that regulate neuronal plasticity and is an important target for the acute and chronic effects of ethanol. However, the specific sites where ethanol interacts with the receptor protein have yet to be fully elucidated. We previously demonstrated that a phenylalanine to alanine mutation in the third transmembrane domain (TM3) of the NR1 subunit decreased the ethanol inhibition of NMDA receptors expressed in HEK293 cells. In this study, we characterized the ethanol inhibition of NMDA receptors containing additional mutations within the TM3 and TM4 domains of the NR1 subunit.Methods:Site‐directed mutagenesis was used to alter specific amino acid residues in the TM3 and TM4 domains of the NR1 subunit. Mutant NR1 subunits were coexpressed with the NR2A subunit in HEK293 cells and examined for alterations in ethanol sensitivity using whole‐cell voltage‐clamp electrophysiology.Results:Replacing phenylalanine at TM3 position 639 in the NR1 subunit (F639) with 9 different amino acids produced functional receptors when coexpressed with the NR2A subunit. All mutants showed a concentration‐dependent inhibition by ethanol (10–100 mM), with the alanine and serine mutants being significantly less sensitive to ethanol. Amino acid substitutions at the F639 site also produced variable changes in the concentration–response relationship to glycine. However, no significant correlation between glycine EC50values and the magnitude of ethanol inhibition was observed. Alanine mutations at TM4 positions 813 (M813A) and 819 (L819A), but not at 817 (F817A), of the NR1 subunit enhanced ethanol inhibition. Substitution of tryptophan for TM4 residues in the NR1 subunit (positions 820–822) that are homologous to a site in the NR2A subunit shown to reduce ethanol inhibition (A825W) had no effect on ethanol sensitivity. However, these NR1 TM4 tryptophan mutants restored the ethanol inhibition of the NR1 TM3 F639A mutant to wild‐type levels in a stepwise fashion.Conclusions:These results indicate that the ethanol sensitivity of NMDA receptors may be regulated by discrete sites within the TM3 and TM4 domains of the NR1 subunit.
Brain Metabolite Concentrations and Neurocognition During Short‐term Recovery from Alcohol Dependence: Preliminary Evidence of the Effects of Concurrent Chronic Cigarette Smoking
Authors: Durazzo Timothy C. , Gazdzinski Stefan , Rothlind Johannes C. , Banys Peter , Meyerhoff Dieter J. 
Published: February 2006

Background: Longitudinal studies of brain tissue metabolite recovery in short‐term abstinent alcoholics have primarily investigated the frontal lobes and cerebellum with variable results. Preliminary proton magnetic resonance spectroscopic imaging (1H MRSI) suggested that chronic cigarette smoking exacerbates alcohol‐induced brain injury in 1‐week abstinent alcoholics. However, the potential effects of chronic cigarette smoking on the recovery of alcohol‐induced brain injury have not been studied.Methods: Multislice short‐echo time 1H MRSI was used to measure longitudinal changes in common brain metabolites in 25 recovering alcohol‐dependent individuals (RA), retrospectively assigned to smoking (n=14) and nonsmoking (n=11) subgroups. Recovering alcohol‐dependent individuals in longitudinal analyses were studied after approximately 7 and 34 days of abstinence from alcohol. In cross‐sectional analyses, 36 RA (19 smokers, 17 nonsmokers) with approximately 34 days of sobriety were compared with 29 light drinkers (LD). Relationships between neurocognition and metabolite concentrations in abstinent RA were also examined.Results: Over 1 month of abstinence from alcohol, RA, as a group, showed significant increases of regional N‐acetylaspartate (NAA; marker of neuronal viability) and choline‐containing compounds (Cho; marker of cell membrane synthesis/turnover) primarily in frontal and parietal lobes. These increases appeared to be driven by nonsmoking RA. Cross‐sectional results indicate that metabolite levels in RA at 35 days of sobriety are not significantly different from those in LD in most regions, except for lower NAA and Cho in parietal WM and subcortical structures. However, metabolite levels at that time appear to be strongly modulated by smoking status. The patterns of metabolite–neurocognition relationships were different for nonsmoking and smoking RA.Conclusions: Within the first weeks of sobriety, regional brain NAA and Cho levels increased, but metabolite levels did not normalize in all brain regions after 35 days of sobriety. Neurobiologic recovery in RA appeared to be adversely affected by chronic smoking. Greater consideration of the effects of continued cigarette smoking on the neurobiologic and neurocognitive recovery of alcohol‐dependent individuals is warranted.
Fatty Acid Ethyl Esters in Human Mononuclear Cells: Production by Endogenous Synthesis Greatly Exceeds the Uptake of Preformed Ethyl Esters
Authors: Alhomsi Khaled , Cluette‐Brown Joanne E. , Laposata Michael 
Published: February 2006

Background: Fatty acid ethyl esters (FAEE) are nonoxidative metabolites of ethanol. They are esterification products of ethanol and fatty acids. Fatty acid ethyl esters have been implicated as important mediators of ethanol‐induced cytotoxicity, organ damage, and disease. In addition, they serve as specific and sensitive biomarkers for ethanol intake. Following ethanol consumption, FAEE are found in circulating blood bound to albumin or/and lipoproteins.Objectives: Using a mononuclear fraction of white blood cells (WBC) exposed to ethanol, we investigated FAEE synthesis. We then determined the amount of uptake of preformed FAEE presented to the cells and compared the amounts of FAEE within the cells that were derived from endogenous synthesis with the amount derived from uptake of exposure FAEE. We also measured the persistence of FAEE within these cells and assessed the fate of the FAEE‐associated fatty acid upon FAEE hydrolysis.Methods: A mononuclear fraction of human WBC was incubated with 25, 50, or 100 mM ethanol for 0.08 to 120 minutes, and FAEE synthesis was measured by gas chromatography/mass spectrometry. In other experiments, mononuclear cells were incubated with 25, 50, and/or 100 μM [3H]ethyl oleate, a representative FAEE species, for 0.08–120 minutes, and FAEE uptake and hydrolysis were measured.Results: The total FAEE formed by treating the cells with 25 mM ethanol, which represents a physiologic dose achievable with excess alcohol intake, greatly exceeded the FAEE within cells derived from uptake of 100 μM ethyl oleate, which represents a supraphysiologic dose. There was hydrolysis of FAEE by human mononuclear cells, with free fatty acids as major metabolites of FAEE hydrolysis. Unlike any other cell type or homogenate studied, the only ethyl ester formed by human mononuclear cells exposed to ethanol was ethyl oleate.Conclusions: There is significant synthesis of FAEE by human mononuclear cells within seconds of exposure to physiologic doses of ethanol. The amount of FAEE in these cells derived from endogenous synthesis greatly exceeds the amount acquired by exogenous uptake.
The Alcohol Content of Wine Consumed in the US and Per Capita Consumption: New Estimates Reveal Different Trends
Authors: Kerr William C. , Greenfield Thomas K. , Tujague Jennifer , Brown Stephan E. 
Published: February 2006

Background:To estimate the mean percentage alcohol content by volume (%ABV) for wine sold in the US and in each state for the years 1962 to 2002, and to apply these to per capita wine sales for the years 1970 to 2002.Method:Estimates of wine‐type mean %ABV are calculated using brand‐level sales and %ABV from one state and are extrapolated to other states and to the US using wine‐type sales.Results:The mean %ABV is found to vary substantially over time and across states, with US means ranging from 16.2% in 1962 to a low of 10.5% in 1991. By 2002, the US mean %ABV had risen to nearly 11.5%. Application of %ABV estimates to the per capita consumption of wine indicated significant differences from previous estimates with lower alcohol intake from wine found for all years after 1980 and 6 year‐to‐year changes in opposite directions.Conclusions:Empirically based estimates of the alcohol content of wine sold in the US show changes over time and differences between states that have significance for epidemiologic monitoring and modeling of the determinants and consequences of alcohol use and for improving comparisons with per capita beer and spirits consumption series.
The Effect of the Real Option to Transfer on the Value of Guaranteed Minimum Death Benefits
Authors: Ulm Eric R. 
Published: February 2006

AbstractVariable annuity contracts frequently have many options and option‐like features embedded in the contracts. Some are obvious, such as guaranteed minimum death benefits (GMDBs), while others are less obviously option‐like. In this article, we consider the effect of the real option to transfer funds between fixed and variable accounts. If a GMDB rider is considered in isolation, it is sometimes in the policyholder's interest to transfer to the fixed fund if the fixed fund earns less than the variable fund in a risk‐neutral world. On the other hand, the option to transfer will not be used if the entire annuity and rider are considered together.
Guarantees in With‐Profit and Unitized With‐Profit Life Insurance Contracts: Fair Valuation Problem in Presence of the Default Option
Authors: Ballotta Laura , Haberman Steven , Wang Nan 
Published: February 2006

AbstractThe purpose of the article is to apply contingent claim theory to the valuation of the type of participating life insurance policies commonly sold in the UK. The article extends the techniques developed by Haberman, Ballotta, and Wang (2003) to allow for the default option. The default option is a feature of the design of these policies, which recognizes that the insurance company's liability is limited by the market value of the reference portfolio of assets underlying the policies that have been sold. The valuation approach is based on the classical contingent claim pricing “machinery,” underpinned by Monte Carlo techniques for the computation of fair values. The article addresses in particular the issue of a fair contract design for a complex type of participating policy and analyzes in detail the feasible set of policy design parameters that would lead to a fair contract and the trade‐offs between these parameters.