bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of Ganaxolone's Anticonvulsant Activity Using a Randomized, Double‐Blind, Presurgical Trial Design
Authors: Laxer Kenneth , Blum David , Abou‐Khalil Basil W. , Morrell Martha J. , Lee David A. , Data Joann L. , Monaghan Edward P. ,   the Ganaxolone Presurgical Study Group
Published: August 2005

Summary: Purpose: A double‐blind, randomized, placebo‐controlled clinical trial to examine the safety, tolerability, and antiepileptic activity of ganaxolone in patients after withdrawal from other antiepileptic drugs during presurgical evaluations was performed.

Methods: Fifty‐two eligible patients were withdrawn from antiepileptic drugs and randomized to receive ganaxolone (24 patients) or placebo (28 patients) for up to 8 days. Ganaxolone was administered at a dose of 1500 mg/d on day 1 and 1875 mg/d on days 2 to 8. Dosing occurred three times per day: immediately after breakfast, lunch, and dinner.

Results: The primary measure of antiepileptic activity was duration of treatment before withdrawal from the trial. Kaplan‐Meier curves depicted a clear separation between treatment groups, with 50% of the ganaxolone‐treated patients completing the entire study, compared with 25% of patients treated with placebo. Intent‐to‐treat survival analyses revealed a trend toward efficacy with ganaxolone (p = 0.0795, log rank test). Covariate analyses revealed a significant treatment effect on survival time in men (p = 0.03). Post‐hoc χ2 probe analyses focusing on patients who completed the entire study revealed a significant difference (p = 0.04) between treatment groups. The tolerability of ganaxolone was similar to that of placebo, with adverse events being reported by 79% of patients in the ganaxolone group and 68% of patients in the placebo group.

Conclusions: Ganaxolone monotherapy was well tolerated for the duration of this clinical trial, and the results provide preliminary evidence that ganaxolone does have antiepileptic activity.
Lateral Asymmetry in Activation of Hypothalamic Neurons with Unilateral Amygdaloid Seizures
Authors: Silveira D. C. , Klein P. , Ransil B. J. , Liu Z. , Hori A. , Holmes G. L. , de LaCalle S. , Elmquist J. , Herzog A. G.
Published: August 2005

Summary: Purpose: Reproductive disorders are unusually frequent among women with temporal lobe seizures. The particular type of disorder may be related to the laterality and focality of epileptiform discharges. Here we examined whether unilateral amygdaloid seizures activate hypothalamic neurons involved in reproductive function and reproductive endocrine secretion in female rats and whether such activation shows lateral asymmetry.

Methods: Numbers of Fos‐immunoreactive (Fos‐ir) neurons in various hypothalamic regions were compared for three groups of animals: (a) unilateral amygdala‐kindled, (b) implanted but unstimulated, and (c) unimplanted.

Results: Fos‐ir neurons showed strong ipsilateral occurrence in the medial preoptic, ventrolateral part of the ventromedial, and ventral premammillary nuclei, sexually dimorphic regions involved in reproductive endocrine regulation. No significant lateral asymmetry was observed for other investigated hypothalamic regions.

Conclusions: Unilateral amygdaloid seizures activate hypothalamic neurons that regulate reproductive endocrine secretion in a laterally asymmetric fashion. This may explain the clinical association of different reproductive endocrine disorders with left and right temporal epileptiform discharges.
Electroclinical Picture of Autosomal Dominant Nocturnal Frontal Lobe Epilepsy in a Japanese Family
Authors: Ito Masatoshi , Kobayashi Kenichiro , Fujii Tatsuya , Okuno Takehiko , Hirose Shinichi , Iwata Hiromi , Mitsudome Akihisa , Kaneko Sunao
Published: August 2005

Summary: Purpose: Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is the first described partial epilepsy syndrome known to be due to a single gene mutation. We found a first Japanese ADNFLE family with a novel mutation of the neuronal nicotinic acetylcholine receptor (nAChR) α4 subunit (CHRNA4) gene. The aim of this report is precisely to describe the electroclinical manifestations of ADNFLE in this family and to compare these findings with those of other families reported previously in the literature.

Methods: Three affected family members were investigated electroclinically by close clinical observation, interictal EEG, video‐EEG monitoring, magnetic resonance imaging, and single‐photon‐emission tomography. Information about other affected family members was obtained from either the spouse or the parents. Mutations within the CHRNA4 gene were examined in seven family members.

Results: The clinical manifestations and diagnostic findings in the members of this family were consistent with ADNFLE. However, there were intrafamilial and interfamilial variations in clinical features. The seizures of the patients were brief tonic seizures, with hyperventilation in children and secondarily generalized tonic–clonic convulsions in adults. The onset of the children's seizures began in infancy and early childhood. The children's seizures were sometimes provoked by movement and sound stimulation, and did not respond to antiepileptic drugs. On the other hand, the adults’ seizures disappeared spontaneously or were easily controlled with carbamazepine. Three children showed hyperactivity, and two children had mild mental retardation. All patients had impaired consciousness during their seizures and no auras. A novel missense mutation (c755C>T) in exon 5 of the CHRNA4 gene was found in four affected family members.

Conclusions: The electroclinical pictures of a Japanese family with ADNFLE were basically the same as those of other families reported, but with slight differences. ADNFLE is probably not uncommon, and it is very likely that there are unidentified patients with this inherited disorder in Japan.
Interpretation of Wada Memory Test for Lateralization of Seizure Focus by Use of 99mTechnetium‐HMPAO SPECT
Authors: Gon Kim Byung , Lee Sang Kun , Kim Joo‐Young , Kang Dong‐Wha , Lee Won‐ou , Song Ho chun , Lee Dong Soo
Published: August 2005

Summary: Purpose: Although the intracarotid amobarbital procedure (IAP) or Wada test is useful in lateralizing seizure focus in patients with temporal lobe epilepsy (TLE), the results of the IAP memory test are frequently nonlateralizing. An insufficient suppression of the medial temporal region contralateral to the seizure focus may contribute to the failure of lateralization. We tried to correlate IAP memory results with the functional changes in the contralateral medial temporal region as measured by single photon emission computed tomography. (SPECT) during IAP.

Methods: We performed a 99mtechnetium‐(Tc) hexamethylene‐propylene‐amine‐oxime (HMPAO) brain SPECT in 19 medial TLE patients during a contralateral IAP (sodium amobarbital injected contralateral to the seizure focus). Regional cerebral blood flow (rCBF) was measured in the contralateral medial temporal region. The amount of decrease in the rCBF was calculated by subtracting the previous measurement from the one obtained with the interictal SPECT.

Results: Ten (53%) patients passed and nine (47%) failed the contralateral IAP. The mean percentage decrease in rCBF was 5.3 ± 5.3%. There was a significant negative correlation between a decrease in the rCBF and the IAP memory‐retention score by Spearman correlation (p =–0.53; p > 0.021). Patients with smaller decreases in rCBF (>5%) more frequently passed the contralateral IAP memory test than did those with larger decreases (80 vs. 22%; p > 0.023).

Conclusions: We suggest that an insufficient suppression of the contralateral medial temporal function is partly responsible for nonlateralizing IAP memory tests. An IAP‐SPECT may be useful in interpreting IAP memory tests for the lateralization of seizure focus in TLE patients.
Sudden Unexplained Death and Injury in Epilepsy
Authors: Ficker David M.
Published: August 2005

Summary: Seizures may be associated with risk of injury or death. Injuries are common in patients with epilepsy, with up to 30% of patients reporting injuries, most commonly blunt trauma and lacerations. Seizures associated with falls increase the risk of injury, but any seizure that is associated with alteration in consciousness may cause injury. Patients with seizures may injure others, especially by causing motor vehicle accidents. Each state has restrictions on driving, requiring seizure‐free intervals that range from 3 to 18 months. Mortality is increased in patients with epilepsy. The standardized mortality ratio is increased two to three times in epilepsy cohorts. Sudden unexplained death in epilepsy (SUDEP) is responsible for 2% to 17% of all deaths in patients with epilepsy, depending on the cohort studied. Population‐based studies of SUDEP show a lower overall SUDEP rate compared with clinical trials or epilepsy referral center cohorts. Overall, the risk of sudden death is increased in the epilepsy population by 24 times compared with the general population. Risk factors for SUDEP may include poorly controlled seizures, early onset of epilepsy, and generalized tonic‐clonic seizures. The pathophysiology of SUDEP is unknown, but animal data suggest apnea may be the initial factor that results in sudden death.
Status Epilepticus: Risk Factors and Complications
Authors: Fountain Nathan B.
Published: August 2005

Summary: Status epilepticus is common and associated with significant mortality and complications. It affects approximately 50 patients per 100,000 population annually and recurs in >13%. History of epilepsy is the strongest single risk factor for generalized convulsive status epilepticus. More than 15% of patients with epilepsy have at least one episode of status epilepticus and low antiepileptic drug levels are a potentially modifiable risk factor. Other risks include young age, genetic predisposition, and acquired brain insults. Fever is a very common risk in children, as is stroke in adults. Mortality rates are 15% to 20% in adults and 3% to 15% in children. Acute complications result from hyperthermia, pulmonary edema, cardiac arrhythmias, and cardiovascular collapse. Long‐term complications include epilepsy (20% to 40%), encephalopathy (6% to 15%), and focal neurologic deficits (9% to 11%). Neuronal injury leading to temporal lobe epilepsy is probably mediated by excess excitation via activation of the N‐methyl‐D‐aspartate (NMDA) subtype of glutamate receptors and consequent elevated intracellular calcium that causes acute necrosis and delayed apoptotic cell death. Some forms of nonconvulsive status epilepticus may also lead to neuronal injury by this mechanism, but others may not. Based on clinical and experimental observations, complex partial status epilepticus is more likely to result in neuronal injury similar to generalized convulsive status epilepticus. Absence status epilepticus is much less likely to result in neuronal injury, and complications because it may be mediated primarily through excess inhibition. Future research strategies to prevent complications of status epilepticus include the study of new drugs (including NMDA antagonists, new drug delivery systems, and drug combinations) to stop seizure activity and prevent acute and delayed neuronal injury that leads to the development of epilepsy.
Uses and Abuses of the EEG in Epilepsy
Authors: Fowle Adrian J. , Binnie Colin D.
Published: August 2005

Summary: Our purpose was to indicate clinical situations in epilepsy in which the EEG provides useful information and those in which it is unhelpful and should be avoided. We performed an overview of the formal evidence available through Medline, Cochrane, and the Internet, as well as a traditional review based on the questions commonly asked of the authors'department in a London teaching hospital. We found that there is insufficient high‐quality evidence to informed decisions regarding EEG utility. The EEG has many uses in epilepsy but, without attention to detail in the referral, may be abused. Good liaison between the referrer and the EEG department is essential to make proper use of the EEG.
Seizure‐Induced Neuronal Necrosis: Implications for Programmed Cell Death Mechanisms
Authors: Fujikawa Denson G. , Shinmei Steve S. , Cai Baiyuan
Published: August 2005

Summary: Purpose: To determine definitively the morphology of neuronal death from lithium‐pilocarpine (LPC)‐and kainic acid (KA)‐induced status epilepticus (SE), and to correlate this with markers of DNA fragmentation that have been associated with cellular apoptosis. Endogenous glutamate release is probably responsible for neuronal death in both seizure models, because neuronal death in both is N‐methyl‐D‐aspartate receptor‐mediated.

Methods: SE was induced for 3 hours in adult male Wistar rats with either LPC or KA, and 24 or 72 hours later the rats were killed. One group of rats had brain sections, stained with hematoxylin and eosin and the terminal deoxynucleotidyl transferase dUTP nick‐end labeling (TUNEL) technique, examined by light microscopy and by electron microscopy. A separate group of rats had DNA extracted from the same brain regions examined by electron microscopy in the first group. The extracted DNA was electrophoresed on an agarose gel with ethidium bromide and was examined for the presence or absence of internucleosomal DNA cleavage (DNA “laddering”).

Results: Twenty‐four and 72 hours after 3 hours of LPC‐ or KA‐induced SE, neuronal death in the hippocampus, amygdala, and piriform, entorhinal, and frontal cortices was morphologically necrotic, in spite of DNA laddering in these regions 24 and 72 hours after SE and positive TUNEL staining in some of the regions 72 hours after SE. Ultrastructurally, necrotic neurons were dark and shrunken, with cytoplasmic vacuoles and pyknotic nuclei with small, irregular, dispersed chromatin clumps.

Conclusions: Our results, together with those of other reports, suggest that programmed cell death‐promoting mechanisms are activated by SE in neurons that become necrotic rather than apoptotic and point to the possibility that such mechanisms may contribute to SE‐induced neuronal necrosis.
Neuroprotective Effects of Estrogens on Hippocampal Cells in Adult Female Rats After Status Epilepticus
Authors: Velíšková Jana , Velíšek Libor , Galanopoulou Aristea S. , Sperber Ellen F.
Published: August 2005

Summary: Purpose: Estrogens have neuroprotective effects in ischemia, stroke, and other conditions leading to neuronal cell death (e.g., Alzheimer's disease). The present study examined whether estrogens may have neuroprotective effects after seizures.

Methods: The kainic acid model was used to determine if estrogens protect hippocampal cells after status epilepticus in adult female rats. Rats were ovariectomized 1 week before hormone replacement. β‐Estradiol benzoate (EB; 2 μg in 0·1 mL of oil) was injected subcutaneously 48 and 24 hours before seizure testing. We administered kainic acid (16 mg/kg intraperitoneally) and behaviorally monitored the rats for 5 hours. After this time, all rats were injected with pentobarbital (50 mg/kg intraperitoneally) irrespective of seizure severity. Some rats received two additional doses of EB, one immediately and one 24 hours after the seizures. Another group of rats received only these two doses of EB after the seizures, and yet another group of rats received pretreatment with the intracellular EB receptor antagonist tamoxifen before each of four EB injections. Control rats received oil instead of EB. Rats were killed 48 hours after seizures. Neuronal damage was evaluated in silver‐impregnated and Nissl‐stained sections.

Results: Estrogen treatment before kainic acid administration significantly delayed the onset of kainic acid–induced clonic seizures, whereas it did not change the onset of status epilepticus compared with oil‐treated controls. Furthermore, estrogen treatment significantly protected against kainic acid–induced seizure‐related mortality. In control rats, examination of Nisslstained and silver‐impregnated slides revealed severe neuronal damage in the vulnerable pyramidal neurons of the hippocampal CA3 subfield and in the hilus of the dentate gyrus. Estrogen pretreatment, as well as the combination of pretreatment and posttreatment, significantly reduced the number of argyrophilic neurons in both the CA3 and the dentate gyrus. Posttreatment only had no protective effects. The data indicate that intracellular EB receptors mediate this type of neuroprotective effect, because the tamoxifen pretreatment abolished EB neuroprotection.

Conclusions: Our results suggest that estrogens can be beneficial in protecting against status epilepticus—induced hippocampal damage. Hormonal conditions may have differential effects on underlying epileptic state in some patients. Therefore, more studies are necessary to determine the prospective therapeutic advantage of hormonal treatment in seizure‐related damage.
Granule Cell Neurogenesis After Status Epilepticus in the Immature Rat Brain
Authors: Sankar Raman , Shin Don , Liu Hantao , Katsumori Hiroshi , Wasterlain Claude G.
Published: August 2005

Summary: Purpose: Several experimental paradigms of seizure induction that produce epilepsy as a consequence have been shown to be associated with the proliferation of dentate granule cells. In developing animals, the acute sequela of hilar damage and the chronic sequelae of spontaneous seizures and mossy fiber synaptic reorganization, in response to status epilepticus, occur in an age‐dependent manner. We investigated seizure‐induced granule cell neurogenesis in developing rat pups to study the association between hilar injury, granule cell neurogenesis, and epilepsy.

Methods: Rat pups of 2 and 3 weeks postnatal age were subjected to lithium‐pilocarpine status epilepticus (LiPC SE). Rats were given bromodeoxyuridine (BrdU; 50 mg/kg intra‐peritoneal) twice daily for 4 days beginning 3 days after SE to label dividing cells. Routine immunocytochemistry and quantification of BrdU labeling by image analysis were performed. Results were compared with previously reported data on cellular injury, mossy fiber sprouting, and spontaneous seizures in rat pups of these ages after LiPC SE.

Results: In 3‐week‐old pups, which demonstrate SE‐induced hilar damage and develop spontaneous seizures accompanied by mossy fiber sprouting, the BrdU‐immunoreactive area (percent) in the subgranular proliferative zone increased to 10·6 ± 2·5 compared with 1·4 ± 0·5 in the control animals (p < 0·05). The 2‐week‐old animals, which show neither hilar damage nor sprouting and rarely develop spontaneous seizures, also showed a comparable extent of SE‐induced neurogenesis [8·0 ± 1·4 (LiPC SE) versus 0·4 ± 0·2 (control), p < 0·05].

Conclusions: Seizure‐induced granule cell neurogenesis does not appear to be a function of seizure‐induced hilar cellular damage. Granule cell neurogenesis induced by SE does not determine epileptogenesis in the developing rat.
Plastic Changes in Neuropeptide Y Receptor Subtypes in Experimental Models of Limbic Seizures
Authors: Vezzani A. , Moneta D. , Mulé F. , Ravizza T. , Gobbi M. , French‐Mullen J.
Published: August 2005

Summary: Purpose: Neuropetide Y (NPY)‐mediated neuro‐transmission in the hippocampus is altered by limbic seizures. The functional consequences of this change are still unresolved and clearly depend on the type of NPY receptors involved. NPY Y2 and Y1 receptors are increased on mossy fiber terminals and decreased on granule cell dendrites after seizures, respectively. We investigated (a) whether seizures modify the NPY Y5 receptors in the hippocampus, and (b) the effect of an agonist at Y2/Y5 receptors and antagonists at Y1 receptors on acute and chronic seizure susceptibility.

Methods: Limbic seizures were induced in rats by electrical stimulation of the dorsal hippocampus, leading to stage 5 kindled seizures, or by intrahippocampal or systemic injections of kainic acid. Pentylentetrazol was administered to epileptic rats to assess their enhanced susceptibility to seizures. NPY Y5 receptor protein was measured in hippocampal homogenates using a specific polyclonal antibody and quantitative Western blotting.

Results: Y5 receptors (57‐kD band) were transiently decreased (23 to 35%) in all hippocampal subregions 2 and 7 days, but not 2·5 hours, after seizures induced by systemic kainic acid. A minor band of 51 kD was reduced significantly in CA3 and dentate gyrus, although it was increased in CA1, 30 days after seizures, suggesting long‐term posttranslational changes in this protein. NPY Y5 receptors were increased by 200% in total homogenate from the stimulated hippocampus 2 days but not 30 days after fully kindled seizures. Intracerebral injections of NPY 13–36 (Y2/Y5 receptor agonist) or BIBP 3225 and BIBO 3304 (selective Y1 receptor antagonists) decreased seizure susceptibility in rats.

Conclusions: These results indicate that NPY Y5 receptors change after limbic seizures and suggest that NPY receptors may provide novel target(s) for the treatment of epilepsy.
Inhibitory Circuits in Human Dysplastic Tissue
Authors: Spreafico R. , Tassi L. , Colombo N. , Bramerio M. , Galli C. , Garbelli R. , Ferrario A. , Russo G. Lo , Munari C.
Published: August 2005

Summary: Purpose: Different types of epilepsies and seizures depend on the nature and location of the primary disturbance and are presumably mediated by different physiopathological mechanisms. We immunocytochemically investigated possible changes in the inhibitory ‐aminobutyric acid (GABA)ergic system in specimens taken from four patients who underwent surgery for intractable epilepsy and presented two different types of focal cortical dysplasia in the temporal lobe.

Methods: The patients were selected on the basis of electro‐clinical, imaging, and routine neuropathological data: two had Taylor focal dysplasia, and two had non‐Taylor dysplasia (microdysgenesia). The study was performed using antibodies against parvalbumin (PV), glutamic acid decarboxylase (GAD), and GABA‐transporter 1 (GAT1).

Results: In the patients with Taylor dysplasia, laminar disorganization of the cortex was associated with the presence of giant neurons and ballooned cells; there was a reduced number of PV‐positive neurons and terminals, the giant neurons were surrounded by clusters of PV‐ and GAD‐positive terminals, and there was an overall reduction in GAT1. Despite the presence of cortical laminar disorganization, no giant or ballooned cells were found in the patients with non‐Taylor microdysgenesia; there was a marked decrease in PV and GAD immunoreactive elements, with a patchy distribution of GAD and GAT1 immunoreactivity but no clustering of PV and GAD terminals.

Conclusions: These results suggest that the two forms of cortical dysplasia are characterized by different and selective morphofunctional alterations in the GABAergic system.
An Overview of the Preclinical Aspects of Topiramate: Pharmacology, Pharmacokinetics, and Mechanism of Action
Authors: Shank Richard P. , Gardocki Joseph F. , Streeter Anthony J. , Maryanoff Bruce E.
Published: August 2005

In this overview, we discuss the discovery and development of topiramate (TPM) as an anticonvulsant, including notable aspects of its chemical, biologic, and pharmacokinetic properties. In particular, we highlight its anticonvulsant profile in traditional seizure tests and animal models of epilepsy and the results of recent electrophysiological and biochemical studies using cultured neurons that have revealed a unique combination of pharmacologic properties of TPM. Finally, we present a hypothesis for the mechanistic basis of the anticonvulsant activity of TPM, which proposes that TPM binds to certain membrane ion channel proteins at phosphory‐lation sites and thereby allosterically modulates channel conductance and secondarily inhibits protein phosphorylation.
Topiramate in the Long‐Term Management of Refractory Epilepsy
Authors: Abou‐Khalil Bassel ,   Topiramate YOL Study Group
Published: August 2005

Purpose: A total of 292 adult patients (mean age, 33 years) with partial and/or generalized seizures previously resistant to antiepileptic drug (AED) therapy (median baseline seizure rate, 12 seizures/month) were treated with open‐label topiramate (TPM) in dosages of 100–1,600 mg/day.

Methods: The mean duration of TPM treatment was 413 days (range, 84–804 days), and the mean TPM dosage was 503 mg/day (range, 100–1,600 mg/day; median TPM dosage, 300 mg/day). Seizure reduction was calculated from seizure counts during the last 3 months and last 6 months of TPM therapy compared with baseline.

Results: Overall, >50% of patients achieved ges;50% seizure reduction. More important, 11 % of patients were seizure‐free for ges;3 months at the last visit; 10% of patients were seizure free for ges;6 months at the last visit. This robust therapeutic response was consistent for patients receiving TPM dosages >400 and <400 mg/day. The most commonly reported adverse events were related to the central nervous system. Over the 2·2‐year treatment period, 19% of patients discontinued TPM therapy because of inadequate seizure control; 32% discontinued because of adverse events. Findings from this study show that TPM is a useful agent for long‐term seizure control, with some patients becoming seizure free for extended periods despite failing previous AED therapy.
Nonfocal Generalized Tonic–Clonic Seizures: Response During Long‐Term Topiramate Treatment
Authors: Montouris Georgia D. , Biton Victor , Rosenfeld William E. ,   Topiramate YTC/YTCE Study Group
Published: August 2005

Purpose: A total of 131 adults and children (mean age, 27 years; range, 3–59 years) with generalized tonic‐clonic seizures (GTCS) of nonfocal origin resistant to other antiepileptic drugs (AEDs) were treated with open‐label topiramate (TPM) after completing double‐blind placebo‐controlled trials.

Results: The mean duration of open‐label TPM treatment was 387 days (range, 14–909 days); the mean TPM dose was 7 mg/kg/day (range, 1–16 mg/kg/day). At the last study visit, the frequency of GTCS was reduced 50% from baseline in 63% of patients and by 75% in 44%. Among patients treated 6 months, 16% were GTCS free ges;6 months despite a pretreatment seizure frequency of one GTCS/week (median). Treatment with TPM was being continued in 82% of patients (n = 107) at the last visit. During treatment periods of up to 2·5 years, 11 (8%) patients discontinued TPM because of adverse events and seven (5%) because of inadequate seizure control.

Conclusions: TPM therapy was well tolerated, and seizure control was maintained with long‐term, open‐label therapy in patients with GTCS, leading to prolonged seizure‐free intervals in some patients with seizures previously resistant to AED therapy.
Limitations in the Medical Treatment of Cryptogenic or Symptomatic Localization‐Related Epilepsies of Childhood Onset
Authors: Aso Kosaburo , Watanabe Kazuyoshi
Published: August 2005

Summary: We retrospectively examined 169 patients who had cryptogenic or symptomatic localization‐related epilepsies (LRE) and were followed‐up for more than 5 years. The probability of seizure control was 0.13 during the first year of treatment, 0.25 during the first 5 years, and 0.09 during the second and third 5 years. No patients who continued to have intractable seizures for 15 years became free of seizures. The onset of LRE at the age of 3 years or less, seizure cluster, mesial temporal sclerosis (MTS), and temporal lobe epilepsy (TLE) were significantly associated with a poor seizure control. If an antiepileptic drug (AED) failed to control seizures, probability of seizure control by the next drug was low, in particular in patients in whom more than 4 AEDs have already been tried, and seizure control could not be expected after a trial of 6 AEDs. A tentative indication of epilepsy surgery for LRE of childhood onset may be 5 years of poor seizure control and/or failure of four AEDs.
Manufacturing Practices and Strategy Integration: Effects on Cost Efficiency, Flexibility, and Market‐Based Performance
Authors: Swink Morgan , Narasimhan Ram , Kim Soo Wook
Published: August 2005

Manufacturing plant managers have sought performance improvements through implementing best practices discussed in World Class Manufacturing literature. However, our collective understanding of linkages between practices and performance remains incomplete. This study seeks a more complete theory, advancing the idea that strategy integration and enhanced manufacturing capabilities such as cost efficiency and flexibility serve as intermediaries by which practices affect performance. Hypotheses related to this thesis are tested using data from 57 North American manufacturing plants that are past winners and finalists in Industry Week's“America's Best” competition (Drickhamer, 2001). The results suggest that strategy integration plays a strong, central role in the creation of manufacturing cost efficiency and new product flexibility capabilities. Furthermore, strategy integration moderates the influences of product‐process development, supplier relationship management, workforce development, just‐in‐time flow, and process quality management practices on certain manufacturing capabilities. In turn, manufacturing cost efficiency and new product flexibility capabilities mediate the influence of strategy integration on market‐based performance. These findings have implications for practice and for future research.
Schedule Recovery: Unplanned Absences in Service Operations*
Authors: Easton Fred F. , Goodale John C.
Published: August 2005

The U.S. service sector loses 2.3% of all scheduled labor hours to unplanned absences, but in some industries, the total cost of unplanned absences approaches 20% of payroll expense. The principal reasons for unscheduled absences (personal illness and family issues) are unlikely to abate anytime soon. Despite this, most labor scheduling systems continue to assume perfect attendance. This oversight masks an important but rarely addressed issue in services management: how to recover from short‐notice, short‐term reductions in planned capacity.

In this article, we model optimal responses to unplanned employee absences in multi‐server queueing systems that provide discrete, pay‐per‐use services for impatient customers. Our goal is to assess the performance of alternate absence recovery strategies under various staffing and scheduling regimes. We accomplish this by first developing optimal labor schedules for hypothetical service environments with unreliable workers. We then simulate unplanned employee absences, apply an absence recovery model, and compute system profits.

Our absence recovery model utilizes recovery strategies such as holdover overtime, call‐ins, and temporary workers. We find that holdover overtime is an effective absence recovery strategy provided sufficient reserve capacity (maximum allowable work hours minus scheduled hours) exists. Otherwise, less precise and more costly absence recovery methods such as call‐ins and temporary help service workers may be needed. We also find that choices for initial staffing and scheduling policies, such as planned overtime and absence anticipation, significantly influence the likelihood of successful absence recovery. To predict the effectiveness of absence recovery policies under alternate staffing/scheduling strategies and operating environments, we propose an index based on initial capacity reserves.
Is there an association between periodontal disease, prematurity and low birth weight? A population‐based study
Authors: Lunardelli Abelardo Nunes , Peres Marco Aurélio
Published: August 2005

Background: The relationship between periodontal diseases in pregnancy and children born prematurely or with low birth weight has been increasingly investigated, showing inconclusive results.

Objectives: To test the link between periodontal disease in pregnant women and low birth weight or prematurity.

Methods: A population‐based, cross‐sectional study was carried out in Southern Brazil. The sample consisted of 449 parturients who were interviewed and examined up to 48 h post‐partum. Three outcomes were investigated: low birth weight, prematurity and prematurity and/or birth weight. Periodontal disease, the exposure, was defined as (i) at least one site with a periodontal pocket; (ii) the presence of pockets at four or more sites. Socio‐demographic information relating to health and maternal habits was collected through a questionnaire and by hospital medical records. Simple and multiple regression analysis was performed.

Findings: There was no statistically significant association between periodontal disease and low birth weight. Periodontal pocket was not associated with low birth weight and/or pre‐term birth after being adjusted. A periodontal pocket in at least one site was associated with prematurity (odds ratio=2.6; 95% confidence interval 1.0–6.9) even after adjusting for maternal schooling, parity, number of previous children of low birth weight, number of pre‐natal consultations and body mass index. After the introduction of variables relating to maternal health during pregnancy, this association disappeared.

Conclusions: No association was found between periodontal disease in the mother and the low birth weight. An association between prematurity and periodontal pockets was found but it was confounded by maternal health variables.
Impact of smoking on the clinical, microbiological and immunological parameters of adult patients with periodontitis
Authors: Apatzidou D. A. , Riggio M. P. , Kinane D. F.
Published: August 2005

Objectives: The aim of the current study was to assess the impact of smoking on the clinical indices, the humoral immune response and the detection frequency of putative periodontal pathogens in patients with periodontitis cross‐sectionally and following therapy.

Material and Methods: Clinical measurements, subgingival plaque samples, gingival crevicular fluid (GCF) and sera were collected from 40 untreated patients with moderate‐to‐advanced chronic periodontitis before and after treatment over a period of 6 months. The treatment consisted of the initial therapy of scaling and root planing. Smoking status was self‐reported and was confirmed by cotinine enzyme inhibition assay (CEIA). Whole‐mouth clinical measurements were recorded with a manual periodontal probe at baseline (BAS) and at 6 months (RAS). Selected‐site analyses were performed on the deepest site in each quadrant before and after therapy and clinical indices were recorded with an electronic pressure‐sensitive probe. GCF sample volume was quantified using the Periotron 6000. Polymerase chain reaction (PCR) was utilized to determine the presence of Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, Prevotella intermedia, Treponema denticola and Tanerella forsythensis in subgingival plaque. Enzyme‐linked immunosorbent assay examined the systemic antibody titres to these bacteria, and thiocyanate disassociation determined the antibody avidity to these organisms.

Results: At baseline, smokers showed significantly less gingival inflammation and lower GCF volume compared with non‐smokers. After treatment, a compromised clinical outcome was noted for smokers in terms of pocket depth reduction and gain in attachment levels. No significant differences in the detection of putative periodontal pathogens in subgingival plaque existed between smokers and non‐smokers. A consistent trend was noted in that smokers had lower sera immunoglobulin G antibody titres to these organisms before and after treatment (statistically significant for A. actinomycetemcomitans). This pattern was less clear when antibody avidities were considered, revealing only small differences, if any, between the two groups of patients.

Conclusion: Current data indicate that smokers with periodontal disease have a suppressed inflammatory response, a significantly less favourable clinical outcome and seem to have an altered host antibody response to antigenic challenge than non‐smokers. In contrast, the subgingival microflora of smokers appears similar to that of non‐smokers.
CORRELATING SHRINKAGE WITH YIELD, WATER CONTENT AND TEXTURE OF PORK HAM BY COMPUTER VISION
Authors: DU CHENG‐JIN , SUN DA‐WEN
Published: August 2005

An automatic method for shrinkage evaluation of pork ham was developed using computer vision. First, a sequence of image‐processing algorithms was developed to estimate the average diameter, short axis, long axis, perimeter, volume and surface area before and after cooking and cooling. This sequence consisted of three steps, i.e., shape extraction, protrusion deletion and measurement. Based on the estimated shape characteristics, three kinds of shrinkage were evaluated as the percentage change before and after a process, i.e., shrinkages caused by the cooking process, cooling process and total shrinkage during the entire cooking and cooling processes. Then the cooking shrinkage was related to cooking loss; the cooling shrinkage to cooling loss and the total shrinkage to yield, water content and texture. It was found that among the three shrinkages, the cooking shrinkage in volume was the highest with up to 9.36%, and was significantly correlated with cooking loss (r = 0.91). The total shrinkage was highly negatively correlated with water content, and had positive correlations with the texture attributes. However, no significant relationships were found between cooling shrinkage and cooling loss, and between total shrinkage and yield.
Effect of Prestrain on Tensile and Fracture Toughness Properties of Line Pipes
Authors: Fukuda Naoki , Hagiwara Naoto , Masuda Tomoki
Published: August 2005

To investigate the mechanical properties of pipeline subjected to plastic deformation, tensile tests and crack-tip-opening displacement (CTOD) tests were conducted on X60, X65, and X80 line pipe steels with uniaxial tensile or compressive prestrain, εpr. The tensile tests revealed that the Bauschinger effect and work hardening were dependent on the yield-to-tensile ratio (Y∕T) of the steels; the change in yield stress due to prestrain linearly depended on the Y∕T of the base metal. A critical CTOD for crack initiation decreased with increasing ∣εpr∣. Compressive prestrain had a larger effect on the reduction of the critical CTOD than tensile prestrain. The test results showed that the reduction in the critical CTOD due to tensile prestrain was predictable with a simplified theoretical model employing a critical fracture strain of the base metal.
Inelastic Postbuckling and Cyclic Behavior of Tubular Braces
Authors: Asgarian B. , Aghakouchack A. A. , Bea R. G.
Published: August 2005

A nonlinear fiber element for the simulation of buckling, post buckling, and hysteric responses of tubular struts is formulated and implemented in the nonlinear program DRAIN-3DX. In this element both material and geometric nonlinearities are considered. The element is applied to simulate post buckling and hysteric response of pinned and fixed tubular struts subjected to cyclic loading. The results are in good agreement with available results, i.e., experiment and other analytical models data in terms of buckling load, load-deformation curve, strength, and stiffness degradation.
Analytical Variance-Based Global Sensitivity Analysis in
Simulation-Based Design Under Uncertainty
Authors: Chen Wei , Jin Ruichen , Sudjianto Agus
Published: August 2005

The importance of sensitivity analysis in engineering design cannot be over-emphasized. In design under uncertainty, sensitivity analysis is performed with respect to the probabilistic characteristics. Global sensitivity analysis (GSA), in particular, is used to study the impact of variations in input variables on the variation of a model output. One of the most challenging issues for GSA is the intensive computational demand for assessing the impact of probabilistic variations. Existing variance-based GSA methods are developed for general functional relationships but require a large number of samples. In this work, we develop an efficient and accurate approach to GSA that employs analytic formulations derived from metamodels. The approach is especially applicable to simulation-based design because metamodels are often created to replace expensive simulation programs, and therefore readily available to designers. In this work, we identify the needs of GSA in design under uncertainty, and then develop generalized analytical formulations that can provide GSA for a variety of metamodels commonly used in engineering applications. We show that even though the function forms of these metamodels vary significantly, they all follow the form of multivariate tensor-product basis functions for which the analytical results of univariate integrals can be constructed to calculate the multivariate integrals in GSA. The benefits of our proposed techniques are demonstrated and verified through both illustrative mathematical examples and the robust design for improving vehicle handling performance.
Improving an Ergonomics Testing Procedure via Approximation-based Adaptive Experimental Design
Authors: Sasena Michael J. , Parkinson Matthew , Reed Matthew P. , Papalambros Panos Y. , Goovaerts Pierre
Published: August 2005

Adaptive design refers to experimental design where the next sample point is determined by information from previous experiments. This article presents a constrained optimization algorithm known as superEGO (a variant of the EGO algorithm of Schonlau, Welch, and Jones) that can create adaptive designs using kriging approximations. Our primary goal is to illustrate that superEGO is well-suited to generating adaptive designs which have many advantages over competing methods. The approach is demonstrated on a novel human-reach experiment where the selection of sampling points adapts to the individual test subject. Results indicate that superEGO is effective at satisfying the experimental objectives.
Metamodeling Development for Vehicle Frontal Impact
Simulation
Authors: Yang R. J. , Wang N. , Tho C. H. , Bobineau J. P. , Wang B. P.
Published: August 2005

Response surface methods or metamodels are commonly used to approximate large computationally expensive engineering systems. Five response surface methods are studied: Stepwise Regression, Moving Least Square, Kriging, Multiquadric, and Adaptive and Interactive Modeling System. A real-world frontal impact design problem is used as an example, which is a complex, highly nonlinear, transient, dynamic, large deformation finite element model. To study the accuracy of the metamodel, the optimal Latin Hypercube Sampling method is used to distribute the sampling points uniformly over the entire design space. The Root Mean Square Error (RMSE) is used as the error indicator. Convergence rate, widely used in the arena of the finite element method for evaluating new element’s performance, was exploited in this vehicle impact example.
Mechanism of Formation Damage at Elevated Temperature
Authors: Schembre J. M. , Kovscek A. R.
Published: August 2005

The pore and grain surface of reservoir rocks often has clay and other fine material attached onto pore walls. It has been long recognized that brine salinity and pH are key factors affecting the attractive forces between pore surfaces and fines. If mobilized particles are assembled in sufficient quantities, they obstruct pore throats and reduce the permeability of the formation. There is anecdotal evidence of substantial fines migration during steam injection enhanced oil recovery operations. As of yet, the mechanism of fines release with temperature is unexplained. The Derjaguin, Landau, Verwey, and Overbeek theory of colloidal stability is used in conjunction with laboratory, core-scale experiments to demonstrate that high temperature, alkaline pH, and low salinity (typical characteristics of steam condensate) are sufficient to induce fines mobilization. Temperature is a key variable in calculations of fines stability. Hot-water floods are performed in Berea sandstone at temperatures ranging from 20°C to 200°C. Permeability reduction is observed with temperature increase and fines mobilization occurs repeatably at a particular temperature that varies with solution pH and ionic strength. A scanning electron microscope is used to analyze composition of the effluent samples collected during experiments. It confirms the production of fine clay material. On the practical side, this study provides design criteria for steam injection operations so as to control fines production.
Uniform Internal Finishing of SUS304 Stainless Steel Bent Tube Using a Magnetic Abrasive Finishing Process
Authors: Yamaguchi Hitomi , Shinmura Takeo , Sekine Megumi
Published: August 2005

This research studies the factors affecting the conditions required for successful uniform internal finishing of SUS304 stainless steel bent tube by a Magnetic abrasive finishing process. In particular, the effects of the magnetic field and ferrous particles were investigated. Local intensification of the magnetic field is accomplished by offsetting the axis of pole rotation from elbow axis. This effect enables local control of the material removal rate, which leads to uniformity in the finished surface regardless of the initial surface conditions. A two-phase finishing process controlling the size of the ferrous particles is proposed to achieve efficient fine surface finishing.
CtsR Is the Master Regulator of Stress Response Gene Expression inOenococcus oeni
Authors: Grandvalet Cosette , Coucheney Françoise , Beltramo Charlotte , Guzzo Jean
Published: August 2005

Although many stress response genes have been characterized inOenococcus oeni, little is known about the regulation of stress response in this malolactic bacterium. The expression of eubacterial stress genes is controlled both positively and negatively at the transcriptional level. Overall, negative regulation of heat shock genes appears to be more widespread among gram-positive bacteria. We recently identified an ortholog of thectsRgene inO. oeni. InBacillus subtilis, CtsR negatively regulates expression of theclpgenes, which belong to the class III family of heat shock genes. ThectsRgene ofO. oeniis cotranscribed with the downstreamclpCgene. Sequence analysis of theO. oeniIOB 8413 (ATCC BAA-1163) genome revealed the presence of potential CtsR operator sites upstream from most of the major molecular chaperone genes, including theclpgenes and thegroESanddnaKoperons. UsingB. subtilisas a heterologous host, CtsR-dependent regulation ofO. oenimolecular chaperone genes was demonstrated with transcriptional fusions. No alternative sigma factors appear to be encoded by theO. oeniIOB 8413 (ATCC BAA-1163) genome. Moreover, apart from CtsR, no known genes encoding regulators of stress response, such as HrcA, could be identified in this genome. Unlike the multiple regulatory mechanisms of stress response described in many closely related gram-positive bacteria, this is the first example wherednaKandgroESLare controlled by CtsR but not by HrcA.