bluuebunny/crossref_metadata_2025 huggingface dataset:
Differentiation of Temporal Lobe Ictal Behavior Associated with Hippocampal Sclerosis and Tumors of Temporal Lobe
Authors: Saygi Serap , Spencer Susan S. , Scheyer Richard , Katz Amiram , Mattson Richard , Spencer Dennis D.
Published: October 2005

Summary: Ictal behavioral characteristics may reflect seizure spread patterns and provide a clue to seizure onset location, between or within specific cerebral lobes. Sequential symptomatology might therefore distinguish patients with hippocampal sclerosis from patients with temporal lobe tumors. To determine ictal behavioral differences in patients of these groups, we analyzed 145 seizures of 33 patients with hippocampal sclerosis (group I) and 79 seizures of 22 patients with temporal lobe tumors (group 11). First appearance of a variety of ictal behavioral characteristics was determined in three phases (first 5 s, 5–60 s, and from 60 s to mental clearing) for patients in both groups. Ipsilateral hand automatisms were significantly more frequent in the first 60 s in group I (p < 0.005). Onset of contralateral head turning was observed in the first 5 s only in group Il (p < 0.05). First appearance of leg automatisms in group I and of oral automatisms in group Il were very rare in phase 2 (p < 0.01, p < 0.005). Time of onset of other ictal behavioral characteristics and duration of seizures were not statistically different between the two groups. Ictal behavioral characteristics varied among and within patients and patient groups, but certain behavioral characteristics were helpful in differentiating these two groups of temporal lobe epilepsy (TLE) patients.
Likelihood of Pregnancy in Individuals with Idiopathic/Cryptogenic Epilepsy: Social and Biologic Influences
Authors: Schupf Nicole , Ottman Ruth
Published: October 2005

Summary: We interviewed 1,558 adults with idiopathic1 cryptogenic epilepsy ascertained from voluntary organizations and 316 of their siblings without epilepsy to determine their personal history of marriage and pregnancy. We examined the effects of seizure type, age at onset, and family history of epilepsy on the sex‐specific likelihood of pregnancy in individuals with idiopathic/cryptogenic epilepsy as compared with their same‐sex siblings. Overall, men with idiopathic/cryptogenic epilepsy were only 36% as likely as male unaffected siblings ever to have fathered a pregnancy. In men, the reduced likelihood of fathering a pregnancy was associated with partial‐onset seizures, early age at onset (<20 years), and a negative family history of epilepsy, and the effects of these epilepsy characteristics appeared to be mediated through reduced marriage rates. Among men with epilepsy who had ever been married, reproductive disadvantage was confined to those with early‐onset (<10 years) partial epilepsy. Overall, women with idiopathiclcryptogenic epilepsy were only 37% as likely ever to have had a pregnancy as female unaffected siblings; this effect was not strongly influenced by seizure type, age at onset, or family history of epilepsy. In women who had ever been married, unlike in men, reduced likelihood of pregnancy persisted, regardless of seizure type, age at onset, or family history of epilepsy.
Provocation of Nonepileptic Seizures by Suggestion in a General Seizure Population
Authors: Bazil C. W. , Kothari M. , Luciano D. , Moroney J. , Song S. , Vasquez B. , Weinreb H. J. , Devinsky O.
Published: October 2005

Summary: Nonepileptic seizures (NES) are common and are often diagnosed at epilepsy centers by video‐EEG recording of both spontaneous and suggestion‐induced episodes, but no study has evaluated provocative testing in a general seizure population. We studied consecutive patients with a tentative diagnosis of epilepsy using saline provocation during video–EEG recording, suggesting that this could produce a typical seizure. Of 52 patients, 40% had no response, 23% had responses unlike their seizures, and 37% had typical episodes (positive test). Patients whose usual episodes resembled complex partial seizures (CPS) were more likely to have NES than were patients with a history of generalized tonic‐clonic seizures (GTC). Of patients with positive provocations, the primary physician predicted NES in 68% of cases. This preliminary study suggests that NES are frequent in a general neurology setting, and that saline provocation is a sensitive method of identifying NES.
Gabapentin (Neurontin) as Add‐on Therapy in Patients with Partial Seizures: A Double‐Blind, Placebo‐Controlled Study
Authors: Anhut H. , Ashman P. , Feuerstein T. J. , Sauermann W. , Saunders M. , Schmidt B. ,   The International Gabapentin Study Group
Published: October 2005

Summary: A multicenter, double‐blind, randomized, placebo‐controlled study evaluated the efficacy and safety of gabapentin (Neurontin, GBP) as add‐on therapy in 272 patients with refractory partial seizures who were receiving one to two standard antiepileptic drugs (AEDs). Efficacy assessments compared the frequency of partial seizures during the 12‐week treatment phase (T) and the 12‐week baseline period (B). The primary analysis compared data for patients receiving GBP 900 mg/day with placebo; the GBP 1,200‐mglday group provided doseresponse data. Efficacy criteria were percentage of change in seizure frequency (PCH), responder rate (percentage of patients with ≥50% reduction in seizure frequency), and response ratio, where RRatio = (T B)/(T + B). Median PCH was–21.8% in the 900‐mg/day group and −17.8% in the 1,200‐mg/day group as compared with −0.3% in the placebo group. Responder rate was 22.9% in the 900‐mg/day group and 10.1% in the placebo group (p = 0.020, Fisher's exact test). Adjusted mean Rratio was‐0.136 in the 900‐mg/day group and −0.025 in the placebo group (p = 0.0046, analysis of variance ANOVA). Results showed slightly greater improvement for the 1,20‐mg/day than for the 900‐mg/day group (RRatio =−0.157, responder rate 28.0%). Adverse events (AE) occurred in 69% of patients in the 900‐mg/day group and in 64% in the 1,200‐mg/day group as compared with 52% in patients receiving placebo as add‐on therapy. The most frequent AE among patients treated with GBP were somnolence, dizziness, and fatigue. Clinical laboratory evaluations showed no clinically important trends and no evidence of hepatic or hematopoietic effects. GBP is safe and effective in treating some patients with refractory partial seizures.
Reduction in Internal Carotid Arterial Blood Flow Velocity in Children During Antiepileptic Drug Therapy with Clinical Dosages
Authors: Futagi Yasuyuki , Otani Kazumasa , Imai Katsumi
Published: October 2005

Summary: We studied the effect of antiepileptic drugs (AEDs) on internal carotid artery (ICA) blood flow velocity, as an index of total cerebral blood flow (CBF). The subjects were 45 newly diagnosed children with febrile convulsion or epilepsy who were seizure‐free for a period long enough not to affect the results. They had no neurologic deficit, received fixed monotherapy, and were examined by a noninvasive Doppler ultrasound method, in comparisonwith 13 age‐matched normal volunteers with no AED. In 30 patients, the measurements were performed before and after AED administration [10 with phenobarbital (PB), 10 with carbamazepine (CBZ), and 10 with valproate (VPA)], and performed before and after AED discontinuation in the remaining 15 patients (all with PB). Normal volunteers underwent the two consecutive examinations with a mean interval equal to that of the entire patient group, and there was no difference in velocity values between the measurements. In patients receiving CBZ or VPA, a significant reduction was noted in blood flow velocity after drug administration. Although velocity values in the patients receiving PB did not change after drug administration, they were significantly increased after complete discontinuation. In the present study, a slight but significant reduction in CBF caused by AED administration at therapeutic doses in children was suggested.
In Vivo and In Vitro Effects of Phenytoin (PHT) on ATPases and [14C]‐PHT Binding in Synaptosomes and Mitochondria from Rat Cerebral Cortex
Authors: Vargas F. , Vargas P. , Aoki K. , Martinez‐Munoz D.
Published: October 2005

Summary: The effect of phenytoin (PHT) on Na+‐K+‐ATPase and Mg2+‐ATPase activities and on [14C]‐PHT binding in vitro to synaptosomal and mitochondrial sub cellular fractions from rat cerebral cortex was studied after chronic PHT treatment. Synaptosomal and mitochondrial fractions were characterized with plasma membrane and mitochondrial enzymatic markers. Synaptoso‐mal Na+‐K+‐ATPase was not affected in vitro by PHT 1–200 μM or by chronic treatment with 2–50 mg/kg/day of the unlabeled drug for 8 days. Mitochondria1 Mg2+‐ATPase was significantly stimulated by PHT after chronic treatment with 5 mg/kg/day for 8 days; reaching maximal effect (76%), at 10–25 mg/kg. PHT had no effect on mitochondrial Mg2+‐ATPase when added in vitro. [14C]‐PHT binding in vitro to the subcellular fractions was determined by dialysis to assess in vivo binding of the unlabeled PHT during chronic treatment. Indeed, [14C]‐PHT bound to synaptosomes was significantly reduced by chronic PHT treatment from 218 ±10 to 119 & 11 pmol/mg protein after 1 week of treatment; a similar effect was obtained after 2–3 weeks with 10 mg/kg/day. Mitochondrial fraction bound 117 ±10 pmol/mg protein labeled PHT. Chronic treatment with unlabeled PHT also reduced the amount of [14C]‐PHT bound to 19.9 ± 2.2 pmol/mg protein. These results show slow reversible PHT in vivo binding to synaptosomes and mitochondrias from rat cerebral cortex, supporting the idea that the modulatory action of PHT on Na+ and Ca2+ permeabilities are mediated through these slow reversible binding proteins. The data also suggest a possible role of intra synaptosomal mitochondria in [Ca2+]i buffering.
Simultaneous and Continuous Measurement of Free Concentration of Valproate in Blood and Extracellular Space of Rat Cerebral Cortex
Authors: Lücke A. , Mayer T. , Altrup U. , Lehmenkiihler A. , Düsing R. , Speckmann E.‐J.
Published: October 2005

Summary: Free concentration of valproate (VPA) was measured simultaneously and continuously in blood and in the extracellular space of cerebral cortex of rats by VPA‐selective microelectrodes. Constant amounts of VPA were injected into the femoral vein with differing duration of injection. Immediately after drug application, the concentration of free VPA in blood and brain increased to a peak value, the degree of which increased with the speed of injection. Ten to 15 min after VPA injection, a plateau value was reached. This plateau value was equal in the extracellular space of cortex and in blood. The data indicate that VPA can “freely” cross the blood‐brain barrier (BBB).
Early Seizures After Acute Stroke: A Study of 1,640 Cases
Authors: Giroud M. , Gras P. , Fayolle H. , André N. , Soichot P. , Dumas R.
Published: October 2005

Summary: We evaluated prospectively the occurrence of seizures within 15 days of a first stroke or transient ischemic episode in 1,640 patients to study relation between seizures and type of stroke. Seizures occurred in 90 patients (5·4%), including 36 (4·4%) of 814 with infarct owing to atheroma, 21 (16·6%) of 126 with infarct owing to cardiogenic embolus, 3 (1%) of 273 owing to lacunar infarct, 5 (1·9%) of 259 owing to transient ischemic attack (TIA), 21 (16·2%) of 129 owing to supratentorial he matoma, and 4 (16·6%) of 24 owing to subarachnoid hemorrhage. Thirteen (14·6%) of 89 subcortical infarcts were associated with seizures. Seizures were the initial sign of stroke in 80 (89%) of 90 cases and were usually single and partial. Seizure symptoms were most often motor, sensory, or visual.
Influence of Additional Therapy with Zonisamide (Excegran) on Protein Binding and Metabolism of Carbamazepine
Authors: Minami Taketsuga , Ieiri Ichiro , Ohtsubo Kenji , Hirakawa Yoshihiro , Ueda Kohji , Higuchi Shun , Aoyama Toshinobu
Published: October 2005

Summary: The influence of comedication with zonisamide (ZNS) on protein binding and carbamazepine (CBZ) metabolism was studied in 16 pediatric epileptic patients. Correlations were evaluated between ZNS daily dose and individual change of level per dose ratio (L/D ratio), free fraction, and carbamazepine‐10,11‐epoxide/CBZ level ratio (CBZEKBZ). Statistical significant negative correlation was observed between LID ratio and ZNS daily dose. Despite alteration in the L/D ratio, the free fraction of CBZ was unaltered in combination with ZNS. To assess the effect of addition of ZNS on CBZ metabolism, the CBZE/CBZ level ratio was compared; this ratio showed a tendency to increase with increase in ZNS dose. Consequently, ZNS is considered to have a significant effect on CBZ metabolism but not on protein binding.
Efficacy and Tolerance of Long‐Term, High‐Dose Gabapentin: Additional Observations
Authors: Handforth Adrian , Treiman David M.
Published: October 2005

Summary: Gabapentin (GBP) has shown antiepileptic efficacy and good tolerance in clinical trials. Much remains to be learned about its clinical use. As a participating center in the US Gabapentin Study Group, we report observations that have practical implications for patient management. Twenty‐three patients with intractable partial‐onset seizures initiated open‐label treatment after a blinded placebo‐controlled add‐on dose efficacy study. In the titration phase, GBP and concurrent antiepileptic drugs (AEDs) were adjusted to achieve optimal efficacy on maximally tolerated GBP doses. Nine patients had no significant improvement in seizure control and discontinued GBP. The remaining 14 patients were observed while treated long‐term with stable‐dose GBP and concurrent AEDs. Improvement was maintained as long as patients were followed: ≤4 years. The protocol‐allowed upper dose limit, 2,400 mg/day, was well tolerated by 16 of 23 patients, indicating that higher doses may be tolerated. GBP discontinuation did not cause rebound increases in seizure frequency. The most common adverse events (AEs) (in 14 of 23) were similar to those induced by concurrent AEDs and responded to reduction of concurrent AEDs. Many patients reported positive psychostimulatory effects. These observations extend previous findings indicating that GBP is an effective and well‐tolerated drug for treatment of partial‐onset seizures.
Differentiating Clinical Features of Right and Left Temporal Lobe Seizures
Authors: Fakhoury Toufic , Abou‐Khalil Bassel , Peguero Edwin
Published: October 2005

Summary: We reviewed 127 seizures in 19 consecutive patients with temporal lobe epilepsy (TLE) documented by EEG/closed‐circuit TV (EEG‐CCTV) monitoring. Ten patients had seizure onset in the right temporal lobe (RTL, 54 seizures), and 9 had seizure onset in the left temporal lobe (LTL, 73 seizures). We compared the clinical characteristics in the two groups and analyzed the seizures for frequency of auras, seizures secondarily generalized, automatisms, tonic head deviation, focal posturing and jerking, ictal speech, and postical manifestations. Automatisms overall were more common in the RTL group, but individual categories (extremity, head and trunk, oroalimentary) were comparable among the two groups. Contralateral focal jerking and tonic head deviation were more common in LTL lobe seizures, as were secondarily generalized seizures. In addition to focal motor symptoms, three features were most statistically significant in distinguishing the two groups: Postictal aphasia occurred exclusively in the LTL group, whereas well‐formed ictal speech and rapid return to baseline postictally were noted only in RTL seizures.
Long‐Term Subdural Strip Electrocorticographic Monitoring of Ictal Déjà Vu
Authors: Weinand Martin E. , Hermann Bruce , Wyler Allen R. , Carter L. Philip , Oommen K. J. , Labiner David , Ahern Geoff , Herring Anne
Published: October 2005

Summary: We report a series of 8 patients with ictal déjà vu. Subdural strip electrocorticographic (ECoG) monitoring localized the ictal epileptogenic focus as follows: right (n = 6) and left (n = 2) mesiotemporal lobe. In all 8 patients, the left hemisphere was dominant for language function based on intracarotid amytal testing. In 6 right‐handed patients, ictal déjà vu was associated with a right temporal lobe focus. However, in the 2 left‐handed patients, the ictal focus was left temporal lobe. Although ictal déjà vu localizes the epileptic focus to temporal lobe, this experiential phenomenon appears to lateralize to the hemisphere nondominant for handedness.
Paradoxical Normalization in Childhood Epilepsy
Authors: Amir N. , Gross‐Tsur V.
Published: October 2005

Summary: We report 5 children aged 2·5 to 9 years with refractory epilepsy who, in the wake of a change in anti‐epileptic drug (AED) regimen, developed paradoxical normalization (PN). Their acute psychiatric symptoms were associated with abrupt seizure cessation and normalization of the EEG. The latency periods between first seizure and advent of psychosis ranged from 1·9 to 7·0 years. Behavioral manifestations were schizophrenialike psychosis in 1, autistic withdrawal in 3, and organic mental syndrome not otherwise specified in 1. PN has heretofore been reported only in adolescents and adults after prolonged periods of poorly controlled seizures. The hypothesized precipitating factors relate to drug‐induced changes in neurotransmitter systems.
Postictal Courses of Cognitive Deficits in Focal Epilepsies
Authors: Helmstaedter C. , Elger C. E. , Lendt M.
Published: October 2005

Summary: Patients with epileptic seizures frequently complain of long‐lasting cognitive impairment after a seizure. We evaluated this issue in 31 patients with epileptic seizures of a frontal (n = 8) or temporal lobe origin [right temporal lobe (RTL) n = 8/left temporal lobe (LTL) n = 151. Seizures were secondarily generalized in 18 patients. Computerized testing of verbal and nonverbal recognition memory was performed before the seizure, directly after postictal reorientation, and 30 min and 1 h later. Repeated testing of 14 healthy persons served as control. The following results were obtained: Depending on seizure generalization, postictal reorientation times were 1–45 min. Frontal lobe seizures showed no effect on postictal memory performances, but verbal and visual recognition memory was significantly decreased after temporal lobe seizures. Decrease in either verbal or visual memory and time of recovery were related to lateralization of seizure onset. Functional recovery after reorientation lasted 30 min to 1 h. The decrease in performance was more severe after generalized seizures. Decision times during memory performance were not significantly affected by the seizures. Temporal lobe seizures lead to circumscribed and long‐lasting memory deficits, which can be assumed to affect patients'capabilities seriously. Preand postictal testing is a useful tool for determining postictal cognitive impairment and in determining the site of seizure onset.
Epidemiology of Infantile Spasms in Sweden
Authors: Sidenvall Ragnar , Eeg‐Olofsson Orvar
Published: October 2005

Summary: We performed a retrospective study of infantile spasms (IS) in 57 children (19 girls and 38 boys) from the east‐central region of Sweden for the period 1987 1991. The incidence was 0.45/1,000newbornsa year, with a spread of 0.17–0.76 between the seven counties included. Forty‐three cases (75%) were symptomatic and 14 (25%) were idiopathic. Cerebral malformations were diagnosed in 8 children, and chromosomal aberrations were diagnosed in 5. In addition, 2 children each were diagnosed as having tuberous sclerosis and neurofibromatosis. At follow‐up, 57% in the idiopathic group had normal development, whereas 91% in the symptomatic group had died or developed a multihandicap. The value of modern neuroradiological techniques for etiological diagnosis is stressed.
Secular Trends and Birth Cohort Effects in Unprovoked Seizures: Rochester, Minnesota 1935‐1984
Authors: Annegers J. F. , Hauser W. A. , Lee J. R‐J. , Rocca R. W. A.
Published: October 2005

Summary: The incidence of idiopathic/lcryptogenic epilepsy and isolated unprovoked seizures has been relatively stable in the population of Rochester, Minnesota, for the 50‐year period 1935 through 1984. In each decade, the age‐specific rates exhibited a consistent U‐shaped pattern of decreasing rates from infancy to age 40–49 and a progressive increase thereafter to a second peak at age 70 years. Males had a 15% higher incidence of cryptogenic unprovoked seizures than females. The most pronounced secular trend was a decrease in the incidence in children aged <10 years for the first 4 decades of the study; however, this trend was interrupted by a slight rebound in the decade 1975–1984. There has been a progressive decrease in the incidence of cryptogenic unprovoked seizures in individuals aged 350 from 1965 through 1984. This decrease paralleled the decrease in cerebrovascular disease in the community. The decrease in idiopathic unprovoked seizures may be related to a concurrent trend in “silent stroke.” Plots and Poisson regression analysis did not show patterns in the incidence of idiopathic unprovoked seizures related to successive birth cohorts. However, significantly lower incidence rates were observed for the 1930–1934 birth cohort, about half that of all others, between the ages of 5 and 54 years.
Interaction Between Two Quantitative Trait Loci Affects Fetal Haemoglobin Expression
Authors: Garner C. , Menzel S. , Martin C. , Silver N. , Best S. , Spector T. D. , Thein S. L.
Published: October 2005

The biological mechanisms controlling complex quantitative traits are likely to be affected by interactions between genetic factors, sometimes referred to as epistasis. The identification of interacting loci through genetic analyse faces many challenges, and few examples of replicated findings of interaction exist for humans and model system organisms. The replication of an interaction, or the non‐independence, of two quantitative trait loci (QTL) affecting the developmental switch from the expression of fetal to adult haemoglobin is reported here. Fetal haemoglobin expression in adults is a highly heritable, yet complex, phenotype. Using a sample of 874 dizygotic twin pairs of European descent, we found linkage to a QTL on chromosome 8 to be conditional on the twin pairs' genotypes at a polymorphism in the β‐globin complex; an interaction originally identified in a large Asian Indian kindred. The β‐globin polymorphism has been previously shown to be associated with fetal haemoglobin levels in adults. This study reports the first known replication of a genetic interaction between QTLs influencing a complex human trait.
The Association of Mitochondrial DNA 5178 C > A Polymorphism with Plasma Lipid Levels Among Three Ethnic Groups
Authors: Lal S. , Madhavan M. , Heng C. K.
Published: October 2005

Mitochondria are eukaryotic cytoplasmic organelles responsible for oxidative phosphorylation. The C to A nucleotide transversion in the NADH dehydrogenase subunit 2 (MT‐ND2) coding region of mitochondrial DNA has been reported to be associated with plasma lipid levels, adult onset diseases and longevity. We have examined the role of this polymorphism in relation to plasma lipid levels and age in a total of 713 healthy individuals belonging to 3 ethnic groups in Singapore. The frequency of the A allele was significantly higher (p < 0.05) among the Chinese (0.15) in comparison to the Malays (0.05) and Indians (0.02). No significant difference in the frequency of the allele was observed between healthy and coronary artery disease subjects, and between age‐stratified subjects. We found that the polymorphism is significantly associated in an ethnic‐ and gender‐specific manner with plasma apoB levels in the Chinese males (p < 0.05). This is the first epidemiological report of the mt5178 C > A polymorphism and its association with plasma lipid levels in Asian populations outside Japan.
SNP Selection for Association Studies: Maximizing Power across SNP Choice and Study Size
Authors: Pardi F. , Lewis C. M. , Whittaker J. C.
Published: October 2005

Selection of single nucleotide polymorphisms (SNPs) is a problem of primary importance in association studies and several approaches have been proposed. However, none provides a satisfying answer to the problem of how many SNPs should be selected, and how this should depend on the pattern of linkage disequilibrium (LD) in the region under consideration. Moreover, SNP selection is usually considered as independent from deciding the sample size of the study. However, when resources are limited there is a tradeoff between the study size and the number of SNPs to genotype. We show that tuning the SNP density to the LD pattern can be achieved by looking for the best solution to this tradeoff. Our approach consists of formulating SNP selection as an optimization problem: the objective is to maximize the power of the final association study, whilst keeping the total costs below a given budget. We also propose two alternative algorithms for the solution of this optimization problem: a genetic algorithm and a hill climbing search. These standard techniques efficiently find good solutions, even when the number of possible SNPs to choose from is large. We compare the performance of these two algorithms on different chromosomal regions and show that, as expected, the selected SNPs reflect the LD pattern: the optimal SNP density varies dramatically between chromosomal regions.
The Significant Increase in Cardiovascular Disease Risk in APOEɛ4 Carriers is Evident Only in Men Who Smoke: Potential Relationship Between Reduced Antioxidant Status and ApoE4
Authors: Talmud P. J. , Stephens J. W. , Hawe E. , Demissie S. , Cupples L. A. , Hurel S. J. , Humphries S. E. , Ordovas J. M.
Published: October 2005

Data from 1668 men (316 cardiovascular disease events) from the Framingham Offspring Study was reanalysed, specifically examining APOE:smoking interactions. Overall hazard ratio (HR) for smoking was 1.95 (1.52, 2.50) compared to non‐smokers. Using ɛ3/3 as a referent group, in non‐smokers HRs for ɛ2 carriers (ɛ2+; 1.04 (0.61, 1.76) and ɛ4 carriers (ɛ4+; 1.04 (0.70, 1.54) showed no major risk increase. In smokers, HRs were 1.96 (1.26, 2.78) in ɛ3ɛ3 men, 3.46 (2.14, 5.60; p = 0.09 for interaction) in ɛ2+ and 3.81 (2.49, 5.84; p = 0.01 for interaction), with a significant interaction between daily cigarette consumption and APOE genotype on risk (p = 0.03). The potential mechanism for this APOEɛ4:smoking interaction was examined in a second study of 728 Caucasian patients with diabetes, where markers of reactive oxygen species were available. APOE genotype was not associated with plasma OX‐LDL or total antioxidant status (TAOS) in non‐smokers. However, in smokers ɛ4+ had 26.7% higher plasma OX‐LDL than other genotypes (APOE:smoking interaction p = 0.04), while ɛ2+ had 28.4% higher plasma TAOS than ɛ3ɛ3 and ɛ4+ combined (APOE:smoking interaction p = 0.026). Although direct extrapolation needs to be considered with caution, these results identify that the cardiovascular disease risk‐raising effect of ɛ4+ is confined to smokers, and a feasible mechanism is presented by the reduced antioxidant capacity/increased OX‐LDL of apoE4.
Assessment of the Role of Genetic Polymorphism in Venous Thrombosis Through Artificial Neural Networks
Authors: Penco S. , Grossi E. , Cheng S. , Intraligi M. , Maurelli G. , Patrosso M. C. , Marocchi A. , Buscema M.
Published: October 2005

Purpose: To assess the role of genetic polymorphisms in venous thrombosis events (VTE) using Artificial Neural Networks (ANNs), a model for solving non‐linear problems frequently associated with complex biological systems, due to interactions between biological, genetic and environmental factors.

Methods: A database was generated from a case‐control study of venous thrombosis, using 238 patients and 211 controls. The database of 64 variables included age, gender and a panel of 62 genetic variants. Three different ANNs were compared, with logistic regression for the accuracy of predicting cases and controls

Results: ANNs yielded a better performance than the logistic regression algorithm. Indeed, through ANNs models, the 62 variables related to genetic variants were first reduced to a set of 9, and then of 3 (MTHFR 677 C/T, FV arg506gln, ICAM1 gly214arg).

Conclusions: The findings of this study illustrate the power of ANN in evaluating multifactorial data, and show that the different sensitivities of the models of elaboration are related to the characteristics of the data. This may contribute to a better understanding of the role played by genetic polymorphisms in VTE, and help to define, if possible, a test panel of genetic variants to estimate an individual's probability of developing the disease.
Characteristics and Outcomes of Older Adults with Community‐Acquired Pneumococcal Bacteremia
Authors: Chi Ru‐Chien , Jackson Lisa A. , Neuzil Kathleen M.
Published: October 2005

Objectives: To describe baseline characteristics and clinical outcomes of older adults with pneumococcal bacteremia, compare the frequency of serious outcomes according to pneumococcal vaccination status, and assess factors associated with mortality.

Design: Population‐based case‐series.

Setting: Group Health Cooperative, a health maintenance organization in Washington State.

Participants: Community‐dwelling adults aged 65 and older with a first episode of pneumococcal bacteremia between 1988 and 2002.

Measurements: Demographic characteristics, underlying medical conditions, vaccination status, and clinical outcomes, including death, hospitalization, length of hospital stay, and postdischarge care, were assessed using chart review.

Results: The mean age of the 200 elderly patients with pneumococcal bacteremia was 78; 61% were female. Forty percent had had chart‐documented pneumococcal vaccination before the onset of bacteremia. The spectrum of clinical severity and consequences was broad. Ten percent were treated as outpatients. Of the 90% who were hospitalized, 16% were admitted to the intensive care unit. All‐cause mortality at 30 days was 11%. Of survivors, 23% were discharged with home services, and another 20% were discharged to a nursing home. After controlling for age, sex, and pneumococcal vaccination status, predictors of death included coronary artery disease (odds ratio (OR)=4.6, 95% confidence interval (CI)=1.4–14.5) and immunocompromising conditions (OR=5.0, 95% CI=1.6–15.7). Outcomes were similar in patients who did and did not receive pneumococcal vaccination.

Conclusion: In this elderly group, pneumococcal bacteremia was associated with substantial morbidity, mortality, and loss of independence. Coronary artery disease and immunocompromising conditions were independent predictors of death.
The Mechanism of Atrial Antiarrhythmic Action of RSD1235
Authors: FEDIDA DAVID , ORTH PETER M.R. , CHEN JANET Y.C. , LIN SHUNPING , PLOUVIER BERTRAND , JUNG GRACE , EZRIN ALAN M. , BEATCH GREGORY N.
Published: October 2005

Introduction: RSD1235 is a novel drug recently shown to convert AF rapidly and safely in patients.1 Its mechanism of action has been investigated in a rat model of ischemic arrhythmia, along with changes in action potential (AP) morphology in isolated rat ventricular myocytes and effects on cloned channels.

Methods and Results: Ischemic arrhythmias were inhibited with an ED50 of 1.5 μmol/kg/min, and repolarization times increased with non‐significant effects on PR and QRS durations. AP prolongation was observed in rat myocytes at low doses, with plateau elevation and a reduction in the AP overshoot at higher doses. RSD1235 showed selectivity for voltage‐gated K+ channels with IC50 values of 13 μM on hKv1.5 (1 Hz) versus 38 and 30 μM on Kv4.2 and Kv4.3, respectively, and 21 μM on hERG channels. RSD1235 did not block IK1 (IC50 > 1 mM) nor ICa,L (IC50= 220 μM) at 1 Hz in guinea pig ventricular myocytes (n = 4–5). The drug displayed mild (IC50= 43 μM at 1 Hz) open‐channel blockade of Nav1.5 with rapid recovery kinetics after rate reduction (10→1 Hz, 75% recovery with τ= 320 msec). Nav1.5 blocking potency increased with stimulus frequency from an IC50= 40 μM at 0.25 Hz, to an IC50= 9 μM at 20 Hz, and with depolarization increasing from 107 μM at −120 mV to 31 μM at −60 mV (1 Hz).

Conclusions: These data suggest that RSD1235's clinical selectivity and AF conversion efficacy result from block of potassium channels combined with frequency‐ and voltage‐dependent block of INa.
Physical education undergraduates and dental trauma knowledge
Authors: Panzarini Sônia Regina , Pedrini Denise , Brandini Daniela Atili , Poi Wilson Roberto , Santos Manoel Ferreira , Correa João Paulo Toscani , Silva Fernando Ferreira
Published: October 2005

Abstract –  The aim of the present study was to assess the level of knowledge of undergraduates from the College of Physical Education (Toledo, Araçatuba) concerning dental avulsion injuries. Data showed that 95% of the respondents did not know what dental avulsion is, 73.5% said they know how to define dental replantation, however, only 26% were able to do it correctly. When asked about first emergency measures after an avulsion, 50% of the respondents said they know what they should do, and the most cited measure was to seek a dentist. When asked about optimal storage media, 45.5% would keep it in a favorable one, and 28% did not know where to keep the tooth until treatment. Only 25.6% indicated a suitable extra‐oral time for replantation; 90.3% of the respondents had received no advice about the emergency management of dental avulsion; 90% said they consider this an important and necessary subject. The results indicated that educational campaigns are necessary to improve the emergency management of dental injuries by those future P.E. professors for a better prognosis of dental replantation.
POLICY AND INTERVENTION CONSIDERATIONS OF A NETWORK ANALYSIS OF STREET GANGS*
Authors: MCGLOIN JEAN MARIE
Published: October 2005

Research Summary:

This study details a network analysis of the street gang landscape in Newark, New Jersey. Using individual gang members as the unit of analysis and multiple layers of associations as the linkages within the networks, the results suggest that the gangs in Newark are loosely organized with pockets of cohesion. In addition, there is variation with regard to individual connectedness within the gangs, and certain gang members emerge as “cut‐points” or the only connection among gang members or groups of gang members.

Policy Implications:

The results lend further credence to the notion that problem analysis should precede gang interventions. In particular, the findings suggest that particular groups of gang members may be amenable to the collective accountability tactic, whereas others may become more cohesive as a consequence. Indeed, an intervention focused on individuals may be more productive in Newark. The cut‐points within gangs are particularly worthy of attention, both for their capacity to act as communication agents for a deterrence message and for their potential vulnerability to the pulling levers strategy.
Acute response to intracisternal bupivacaine in patients with refractory pain of the head and neck
Authors: Lambert Gavin , Elam Mikael , Friberg Peter , Lundborg Christopher , Gao Sinsia , Bergquist Jonas , Nitescu Petre
Published: October 2005

Continuous intracisternal infusion of bupivacaine for the management of intractable pain of the head and neck is effective in controlling pain in this patient group. With the catheter tip being located at the height of the C1 vertebral body, autonomic regulatory information may also be influenced by the infusion of bupivacaine. By combining direct sampling of cerebrospinal fluid (CSF), via a percutaneously placed catheter in the cisterna magna, with a noradrenaline and adrenaline isotope dilution method for examining sympathetic and adrenal medullary activity, we were able to quantify the release of brain neurotransmitters and examine efferent sympathetic nervous outflow in patients following intracisternal administration of bupivacaine. Despite severe pain, sympathetic and adrenal medullary activities were well within normal range (4.2 ± 0.6 and 0.7 ± 0.2 nmol min−1, respectively, mean ±s.e.m.). Intracisternal bupivacaine administration caused an almost instantaneous elevation in mean arterial blood pressure, increasing by 17 ± 7 mmHg after 10 min (P< 0.01). Heart rate increased in parallel (17 ± 5 beats min−1), and these changes coincided with an increase in sympathetic nervous activity, peaking with an approximately 50% increase over resting level 10 min after injection (P< 0.01). CSF levels of GABA were reduced following bupivacaine (P< 0.05). CSF catecholamines and serotonin, and EEG, remained unaffected. These results show that acutely administered bupivacaine in the cisterna magna of chronic pain sufferers leads to an activation of the sympathetic nervous system. The results suggest that the haemodynamic consequences occur as a result of interference with the neuronal circuitry in the brainstem. Although these effects are transient, they warrant caution at the induction of intracisternal local anaesthesia.
Hypoxic pulmonary vasoconstriction: mechanisms and controversies
Authors: Aaronson Philip I. , Robertson Tom P. , Knock Gregory A. , Becker Silke , Lewis Tristan H. , Snetkov Vladimir , Ward Jeremy P. T.
Published: October 2005

The pulmonary circulation differs from the systemic in several important aspects, the most important being that pulmonary arteries constrict to moderate physiological (∼20–60 mmHg PO2) hypoxia, whereas systemic arteries vasodilate. This phenomenon is called hypoxic pulmonary vasoconstriction (HPV), and is responsible for maintaining the ventilation–perfusion ratio during localized alveolar hypoxia. In disease, however, global hypoxia results in a detrimental increase in total pulmonary vascular resistance, and increased load on the right heart. Despite many years of study, the precise mechanisms underlying HPV remain unresolved. However, as we argue below, there is now overwhelming evidence that hypoxia can stimulate several pathways leading to a rise in the intracellular Ca2+ concentration ([Ca2+]i) in pulmonary artery smooth muscle cells (PASMC). This rise in [Ca2+]i is consistently found to be relatively small, and HPV seems also to require rho kinase‐mediated Ca2+ sensitization. There is good evidence that HPV also has an as yet unexplained endothelium dependency. In this brief review, we highlight selected recent findings and ongoing controversies which continue to animate the study of this remarkable and unique response of the pulmonary vasculature to hypoxia.
An Algorithmic Strategy for Automated Generation of Multicomponent Software Tools for Virtual Manufacturing
Authors: Bless Patrick N. , Kapoor Shiv G. , DeVor Richard E. , Klabjan Diego
Published: October 2005

This paper describes an algorithmic strategy to facilitate the generation of multicomponent software tools for computer-aided manufacturing (CAM) and virtual manufacturing (VM). Components that are often used to build CAM and VM applications include a wide range of domain-specific knowledge sources and also more general utility components with often very heterogeneous characteristics. The identification of a suitable and compatible set of these components is the first and arguably most important step during the development process of any CAM or VM application. This paper presents an algorithmic strategy that automates this development step by solving a time-expanded network problem, referred to as the component set identification (CSI) problem. A definition of the CSI problem, a mathematical formulation, a solution procedure, and some computational results are presented. Finally, an application to predict hole quality in drilling is used to illustrate the functionality of the proposed algorithmic strategy.
The Effects of Post-Weld Cold Working Processes on the Fatigue Strength of Low Carbon Steel Resistance Spot Welds
Authors: Spitsen R. , Kim D. , Flinn B. , Ramulu M. , Easterbrook E. T.
Published: October 2005

The investigation on the use of a post-weld cold working process to improve fatigue strength of low carbon steel resistance spot welds is presented. The cold working process generates uniform and consistent large zones of compressive residual stresses in resistance spot-welded low carbon steel structures using a specially designed indentation device. The effect of the indentation process parameters on the mechanical properties of the resistance spot weld was investigated. Comparisons of the mechanical properties and qualitative results between the as-resistance spot-welded specimens and the post-weld cold worked resistance spot-welded specimens have been made in this investigation. Fatigue testing was also conducted to evaluate the effect of post-weld cold working process on the fatigue characteristics of resistance spot welds. Results showed that a significant improvement in the fatigue strength has been achieved through the post-weld cold working process.
Modeling and On-Line Estimation of Electrode Wear in Resistance Spot Welding
Authors: Li Wei
Published: October 2005

Electrode wear is inherent in the resistance spot welding process. It determines the electrical and mechanical contact condition and thus strongly affects the resistance spot weld quality. A practical approach to minimizing the electrode wear effect is to compensate the welding current as the electrodes wear. However, the existing methods for welding current compensation rely on either a predetermined stepper schedule or an expulsion detection algorithm. These methods are not reliable since the welding current is not determined based on the contact condition for each weld made in the welding process. This paper presents an on-line electrode wear estimation approach to determining the contact condition and the welding current needed to make every weld a good weld during the entire life of the electrodes. In the study, an incrementally coupled finite element simulation was first formulated to analyze the contact area behavior in the resistance spot welding process. A lumped parameter model was then developed to characterize the contact area change with the dynamic resistance measurement. A calibration and an estimation algorithm were subsequently devised for on-line applications. The proposed approach has been validated with experimental data. The results have shown that the estimation algorithm is robust under various process conditions including both welding current and electrode force.
Development of a Six-Degree-of-Freedom Geometric Error Measurement System for a Meso-Scale Machine Tool
Authors: Lee Sang Won , Mayor Rhett , Ni Jun
Published: October 2005

This paper presents the development of a six-degree-of-freedom (DOF) geometric error measurement (6GEM) system that can be applied to the simultaneous measurement of six geometric error components of the moving axes of a meso-scale machine tool (mMT). The system consists of a laser module constructed by a cube beam splitter and a pigtailed laser diode, three two-dimensional position sensitive detectors (PSDs), and an additional cube beam splitter. The laser module moving with the positioning system of the developed mMT testbed generates two perpendicular laser beams, one of which is further divided into two laser beams at the second cube beam splitter. These three laser beams are detected by the three PSDs, and the full pose of the laser module is then calculated simultaneously by forward and inverse kinematic computations. The calculated full pose of the laser module is translated into six-DOF geometric errors of the mMT testbed. A series of experiments are performed to demonstrate the effectiveness and accuracy of the proposed 6GEM system. The experimental results show that the measurement accuracy of the 6GEM system was better than ±0.6μm for translational error components and ±0.6arcsec for angular error components.
Computer Modeling of Electromagnetic Fields and Fluid Flows for Edge Containment in Continuous Casting
Authors: Chang Fon-Chieh , Hull John R.
Published: October 2005

A computer model was developed to predict eddy currents and fluid flows in molten steel. The model was verified by comparing predictions with experimental results of liquid-metal containment and fluid flow in electromagnetic (EM) edge dams (EMDs) designed at Inland Steel (Ispat Industries Ltd.) for twin-roll casting. This mathematical model can greatly shorten casting research on the use of EM fields for liquid metal containment and control. It can also optimize the existing casting processes and minimize expensive, time-consuming full-scale testing. The model was verified by comparing predictions with experimental results of liquid metal containment and fluid flow in EM edge dams designed at Inland Steel (Ispat Industries Ltd.) for twin-roll casting. Numerical simulation was performed by coupling a three-dimensional (3D) finite-element EM code (ELEKTRA) and a 3D finite-difference fluids code (CaPS-EM) to solve Maxwell’s equations, Ohm’s law, Navier-Stokes equations, and transport equations of turbulence flow in a casting process that uses EM fields. ELEKTRA is able to predict the eddy-current distribution and EM forces in complex geometry. CaPS-EM is capable of modeling fluid flows with free surfaces and dynamic rollers. The computed 3D magnetic fields and induced eddy currents in ELEKTRA are used as input to flow-field computations in CaPS-EM. Results of the numerical simulation compared well with measurements obtained from both static and dynamic tests.
Attractive Fixture System Based on Magnetic Field and Friction Force for Numerically Controlled Machining of Paper Honeycomb Core
Authors: Ke Yinglin , Liu Gang
Published: October 2005

In order to improve the precision of machining and reduce the processing cost of paper honeycomb core, a new method is presented to fix the honeycomb core work piece to the working platform using magnetic and frictional forces. In this method, iron powder is used as a medium instead of the traditional adhesive-based material to achieve the bonding between the work piece and the working platform. Iron powder is poured into honeycomb cells until it reaches the desired height using a numerically controlled iron powder feeder system. In addition, a magnetic working platform is manufactured and placed on top of the station of the milling machine. The magnetic field produced by the magnetic working platform is leaded to the iron powder while the magnetic field control system switches on. More precisely, the mutual magnetic attraction between the iron powders located in different cells of the honeycomb and between the iron powder and the platform is generated. While cutting force is applied to the work piece, two types of friction force occur. One is between the iron powder and the wall of the honeycomb cells, and other one is between the work piece and the working platform. Once the resultant friction force balances the machining load, the work piece will be then fixed to the platform. In this paper, a new bonding system based on the new method is introduced and demonstrated.
Uncertainty Analysis for Fiber Permeability Measurement
Authors: Dong Chensong
Published: October 2005

An uncertainty study for fiber permeability measurement is presented in this paper. The sources of uncertainty were identified. This paper focuses on the instrument and environmental uncertainties. The parameter uncertainties of both unsaturated and saturated measurements were estimated based on instrument accuracy limitations and environmental influences. Their influences on the permeability uncertainty were investigated by uncertainty propagation and Monte Carlo simulation. The significant factors affecting the permeability measurement uncertainty were identified. The results show that (1) unsaturated measurement has a higher accuracy than saturated measurement; (2) the significant factors affecting measurement results are pressure and viscosity. Based on the simulation results, the approaches to reduce measurement uncertainty were proposed.