bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.
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

Summary: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

Summary: 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

Summary: 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.
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

ABSTRACTManufacturing 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

ABSTRACTThe 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.