bluuebunny/crossref_metadata_2025 huggingface dataset:
Mossy Fiber Zinc and Temporal Lobe Epilepsy: Pathological Association with Altered “Epileptic”γ‐Aminobutyric Acid A Receptors in Dentate Granule Cells
Authors: Coulter Douglas A.
Published: August 2005

Summary: Temporal lobe epilepsy is associated with circuit rearrangements within the hippocampus. Mossy fibers sprout and pathologically innervate the inner molecular layer of the dentate gyrus, providing a recurrent excitatory pathway not present in the control brain. In addition to releasing glutamate, these recurrent collaterals also release zinc, which can accumulate in high concentrations in the extracellular space. Accompanying these dentate gyrus circuit rearrangements are alterations in the subunit expression patterns and pharmacology of γ‐aminobutyric acid A (GABAA) receptors in dentate granule cells. In normal, control granule cells, GABAA receptors are zinc insensitive as a result of high levels of expression of the α1 subunit in these cells. In epileptic brain, expression of α1 subunits decreases and expression of α4 and δ subunits increases, leading to the assembly of GABAA receptors that are exquisitely zinc sensitive. This temporal and spatial association of the expression of zinc‐sensitive GABAA receptors and the emergence of a zinc‐delivery system unique to the epileptic hippocampus has led to the formulation of an hypothesis that suggests that zinc release during repetitive activation of the dentate gyrus may lead to a catastrophic failure of inhibition under conditions mediating seizure initiation. This could contribute to the limbic hyperexcitability characteristic of temporal lobe epilepsy.
Self‐Sustaining Status Epilepticus: A Condition Maintained by Potentiation of Glutamate Receptors and by Plastic Changes in Substance P and Other Peptide Neuromodulators
Authors: Wasterlain Claude G. , Liu Hantao , Mazarati Andrey M. , Baldwin Roger A. , Shirasaka Yukiyoshi , Katsumori Hiroshi , Thompson Kerry W. , Sankar Raman , de Vasconselos Anne Pereira , Nehlig Astrid
Published: August 2005

Summary: We describe a model of self‐sustaining status epilepticus (SSSE) induced by stimulation of the perforant path in free‐running rats. In this model, seizures can be transiently suppressed by intrahippocampal injection of a blocker of α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid/kainate synapses but return in the absence of further stimulation when the drug ceases to act. However, seizures are irreversibly abolished by blockers of N‐methyl‐d‐aspartate receptors given locally or systemically. SSSE is enhanced by substance P and its agonists and blocked by its antagonists. SSSE induces novel expression of substance P‐like immunoreactivity in hippocampal principal cells. These changes and those in other limbic peptides may contribute to the maintenance of SSSE and to the modulation of hippocampal excitability during epileptic seizures.
Neurons Recorded from Pediatric Epilepsy Surgery Patients with Cortical Dysplasia
Authors: Mathern Gary W. , Cepeda Carlos , Hurst Raymond S. , Flores‐Hernandez Jorge , Mendoza Delia , Levine Michael S.
Published: August 2005

Summary: Purpose: Cortical dysplasia (CD) is a common pathological substrate in patients with early‐onset childhood epilepsy. In CD tissue, little is known about the mechanisms responsible for cellular hyperexcitability. In this study, we report initial electrophysiological and morphological observations from normal and dysmorphic cells in pediatric CD patients.

Methods: Neocortical “most” and “least” epileptogenic areas were sampled based on neuroimaging and electrocorticography from 15 CD patients (ages 0.3 to 14 years). Whole‐cell voltage clamp recordings combined with infrared videomicroscopy sampled abnormal cells (cytomegalic neurons, cells with bifurcated dendrites, disoriented pyramidal cells, etc.) compared with normal‐appearing neurons from the same patient. Cells were filled with biocytin, and adjacent tissue blocks were stained for neuronal and glial markers.

Results: About 15% of the 161 recorded cells were abnormal in appearance. Abnormal cells showed electrophysiological irregularities ranging from intrinsic cellular hyperexcitability to hyposensitivity after application of ionotropic receptor agonists. Other findings included increased excitatory postsynaptic currents and alterations in γ‐aminobutyric acid reversal potentials.

Conclusions: In pediatric CD tissue, these preliminary results indicate that abnormal‐appearing cells showed abnormalities in electrophysiological measures compared with normal‐appearing neurons. The abnormalities varied from hyperexcitability to hypoexcitability. More detailed results and conclusions will be forthcoming as additional patient material is analyzed.
Loss of Hilar Mossy Cells in Ammon's Horn Sclerosis
Authors: Blümcke I. , Suter B. , Behle K. , Kuhn R. , Schramm J. , Elger C. E. , Wiestler O. D.
Published: August 2005

Summary: Purpose: Hilar mossy cells represent an important excitatory subpopulation of the hippocampal formation. Several studies have identified this cell type as particularly vulnerable to seizure activity in rat models of limbic epilepsy. Here we have subjected hilar mossy cell loss in the hippocampus of patients with chronic temporal lobe epilepsy (TLE) to a systematic morphological and immunohistochemical analysis.

Methods: Hippocampal specimens from 30 TLE patients were included; 21 patients presented with segmental neuronal cell loss [Ammon's horns clerosis (AHS)] and 8 with focal lesions (tumors, scars, malformations) not involving the hippocampus proper. In one additional TLE patient, no histopathological alteration could be observed. Surgical specimens from tumor patients without epilepsy (n = 2) and nonepileptic autopsy brains (n = 8) were used as controls. Hilar mossy cells in the human hippocampus were visualized using a novel polycloncal antiserum directed against the metabotropic glutamate receptor subtype mGluR7b or by intracellular Lucifer Yellow injection, confocal laser scanning microscopy, and three‐dimensional morphological reconstruction.

Results: Compared with controls, a significant loss of mGluR7 immunoreactive mossy cells was observed in patients with AHS (p < 0·05). In contrast, TLE patients with focal lesions but structurally intact hippocampus demonstrated only a discrete, nonsignificant reduction of this neuronal subpopulation. This observation was confirmed by analysis of 62 randomly injected hilar neurons from AHS patients, in which we were unable to detect neurons with a morphology like that of hilar mossy cells.

Conclusion: Our present data indicate significant hilar mossy cell loss in TLE patients with AHS. In contrast, hilar mossy cells appear to be less vulnerable in patients with lesion‐associated TLE. Although the significance of mGluR7 immunoreactivity in mossy cells remains to be studied, loss of this cell population is compatible with alterations in hippocampal networks and regional hyperexcitability as pathogenic mechanism of AHS and TLE.
Role of Nitric Oxide in the Epileptogenesis of EL Mice
Authors: Murashima Yoshiya L. , Yoshii Mitsunobu , Suzuki Jiro
Published: August 2005

Summary: Purpose: To understand the role of nitric oxide (NO) in the regulation of seizures, we measured the extracellular levels of the NO metabolites nitrite and nitrate as indices of NO generation in the parietal cortex, hippocampus, and temporal cortex of EL mice. Furthermore, alterations of neuronal, endothelial, and inducible nitric oxide synthetase (nNOS, eNOS, and iNOS, respectively) were observed to correlate them with epileptogenesis.

Methods: EL mice of 20 weeks and 30 weeks of age (before and after the establishment of epileptogenesis, respectively) were used. Nitrite was quantified using the specific absorbancy of diazo dye. NOS isoenzymes (nNOS, iNOS, and eNOS) were also investigated in the hippocampus during development until mice were 30 weeks old. Samples (total protein, 8·33 to 8·43 μg) were separated by sodium dodecyl sulfate—polyacrylamide gel electrophoresis and identified by immunoblotting.

Results: EL mice that experienced repetitive seizures showed a remarkable increase in nitrite in the hippocampus at 30 weeks of age compared with EL mice that had no experience of seizures. nNOS and iNOS were major and minor components, respectively, and both increased in parallel with the development of epileptogenesis. eNOS was not detectable.

Conclusions: Excess iNOS (and subsequent increase in harmful NO) and deficient eNOS (and subsequent decrease in NO identified as an endothelium‐derived relaxing factor) may work together to form a focus complex.
Cellular Actions of Topiramate: Blockade of Kainate‐Evoked Inward Currents in Cultured Hippocampal Neurons
Authors: Gibbs John W. , Sombati Sompong , DeLorenzo Robert J. , Coulter Douglas A.
Published: August 2005

Purpose: This study was undertaken to evaluate the effects of topiramate (TPM) on excitatory amino acid‐evoked currents.

Methods:Kainate and N‐methyl‐d‐aspartate (NMDA) were applied to cultured rat hippocampal neurons by using a concentration‐clamp apparatus to selectively activate the AMPA (α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid)/kainate and NMDA receptor subtypes, respectively. The evoked membrane currents were recorded by using perforated‐patch whole‐cell voltage‐clamp techniques.

Results:TPM partially blocked kainate‐evoked currents with an early‐onset reversible phase (phase I) and a late‐onset phase (phase II) that occurred after a 10‐ to 2‐min delay and did not reverse during a 2‐h washout period. Application of dibutyryl cyclic adenosine monophosphate (cAMP; 2 mM) during washout after phase II block enhanced reversal, with the kainate current amplitude being restored by =50%. Phase II but not phase I block was prevented by prior application of okadaic acid (1 μM), a broad‐spectrum phosphatase inhibitor, suggesting that phase II block may be mediated through interactions with intracellular intermediaries that alter the phosphorylation state of kainate‐activated channels. Topiramate at 100 μM blocked kainate‐evoked currents by 90% during phase II, but had no effect on NMDA‐evoked currents. The median inhibitory concentration (IC50) values for phase I and II block of kainate currents were 1·6 and 4·8 μM, respectively, which are within the range of free serum levels of TPM in patients.

Conclusions:The specific blockade of the kainate‐induced excitatory conductance is consistent with the ability of TPM to reduce neuronal excitability and could contribute to the anti‐convulsant efficacy of this drug.
Topiramate Modulates GABA‐Evoked Currents in Murine Cortical Neurons by a Nonbenzodiazepine Mechanism
Authors: White H. Steve , Brown S. Douglas , Woodhead J. H. , Skeen Gwendolyn A. , Wolf Harold H.
Published: August 2005

Purpose: These studies further investigate the ability of topiramate (TPM) to enhance γ‐aminobutyric acid (GABA)‐mediated inhibition through a benzodiazepine‐insensitive pathway.

Methods: Topiramate (30 and 100 μM) enhancement of GABA (1 μM)‐evoked currents in primary cultures of mouse cortical neurons was studied by using whole‐cell electrophysiologic techniques. Results obtained with TPM (30 μM) were compared with those obtained with clonazepam (CZP; 1 μM).

Results: Topiramate enhanced GABA currents in a subset of cortical neurons tested. In addition, TPM enhanced GABA‐evoked currents in CZP‐insensitive neurons, and CZP was effective in a subset of TPM‐insensitive neurons. Related studies in vivo demonstrated that intraperitoneal (i.p.) administration of either TPM (25 mg/kg) or CZP (0.012 mg/kg) increases pentylenetetrazol (PTZ) seizure threshold. This effect of CZP, but not TPM, was reversed by the benzodiazepine (BZD) antagonist flumazenil (FMZ; 40 mg/kg, i.p.).

Conclusions: These results indicate that GABAA‐receptor sensitivity to TPM is not dependent on the presence of BZD sensitivity. Enhancement of GABA‐mediated inhibition through a BZD‐insensitive pathway may represent one mechanism through which TPM exerts its anticonvulsant action.
Differential Sensitivity of Recombinant GABAA Receptors Expressed in Xenopus Oocytes to Modulation by Topiramate
Authors: Gordey Marina , DeLorey Timothy M. , Olsen Richard W.
Published: August 2005

Purpose: This study evaluated the modulatory effects of topiramate (TPM) on various subtypes of recombinant rat γ‐aminobutyric acid A (GABAA) receptors expressed in Xenopus oocytes.

Methods: Specific subunits of GABAA receptors were expressed in Xenopus oocytes. Voltage‐clamp recordings of currents were performed after application of TPM (1–100 μM) to these oocytes in the presence or absence of GABA.

Results: In a concentration‐dependent fashion, TPM (1–100 μM) reversibly inhibited GABA‐evoked Cl− currents in oocytes expressing either α1β2γ2S and α2β2γ2S recombinant GABAA receptors and reduced the current‐fading rate in α1β2γ2S‐expressing oocytes. Topiramate was effective at GABA concentrations of 1–10 μM but not at 100 μM. Topiramate (1–100 μM) potentiated GABA‐evoked Cl− currents and increased the fading rate in oocytes expressing the α6β2γ2S GABAA receptor. It had no effect on Cl− currents mediated through the α4β2γ2S receptor or through the mixed population of GABAA receptors expressed from rat brain mRNA. In general, the observed effects of TPM were more pronounced on fading rates than on peak Cl− currents.

Conclusions: These results indicate that TPM may affect desensitization of GABAA receptors as assessed by changes in the fading rates of GABA‐evoked Cl− currents, possibly by effects on second‐messenger systems.
Topiramate Blocks Kainate‐Evoked Cobalt Influx into Cultured Neurons
Authors: Skradski Shana , White H. Steve
Published: August 2005

Purpose: This study evaluated topiramate (TPM) antagonism of glutamate receptors activated by kainate.

Methods: The ability of TPM (3–30 μM) to attenuate kainate (300 μM)‐activated cobalt (Co2+) flux through nonselective cation channels permeable to Co2+, Mn2+, and Ca2+ into cultured cerebellar granule neurons [9–14 days in vitro (div)] was investigated. Results were compared with those obtained with the non‐N‐methyl‐d‐aspartate (non‐NMDA) antagonist 6,7‐dinitroquinoxalone‐2,3‐dione (DNQX) (10 μM).

Results: Topiramate produced a concentration‐ and time‐dependent inhibition of Co2+ uptake into cerebellar granule cells cultured 9–11 div. Inhibition was evident at 10 μM, and complete inhibition was observed at 30 μM. Maximal inhibition of Co2+ uptake required pretreatment with TPM for ges;30 minutes before stimulation by kainate. The effect of 30 μM TPM on Co2+ uptake was similar to that of 10 μM DNQX. However, TPM, unlike DNQX, did not affect kainate‐evoked Co2+ uptake into older neurons (i.e., 13–14 div).

Conclusions: These results provide additional support for an antagonistic effect of TPM on some types of α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐proprionic acid (AMPA) and/or kainate receptors, and specifically suggest that TPM interacts with a Ca2+‐permeable non‐NMDA receptor that is develop‐mentally regulated. This observation may provide insight into the molecular biology underlying the pathophysiology of seizure disorders and antiepileptic drug resistance.
Modulation of High‐Voltage–Activated Calcium Channels in Dentate Granule Cells by Topiramate
Authors: Zhang Xiao‐lei , Velumian Alexander A. , Jones Owen T. , Carlen Peter L.
Published: August 2005

Purpose: In this study, we assessed the effects of topiramate (TPM) on high‐voltage‐activated calcium channel (HVACC) currents in vitro.

Methods: HVACC currents were recorded from rat dentate gyrus granule cells by using whole‐cell patch‐clamp techniques. The biophysical properties of HVACCs were used to separate voltage‐activated Ca2+ currents into different subtypes. Three concentrations of TPM were tested: 1, 10, and 50 μM.

Results: TPM inhibited L‐type currents and was more effective at 10 μM than at 50 μM, suggesting that there may be an optimal concentration at which TPM decreases L‐type currents. Non‐L‐type currents were transiently increased by TPM at a high concentration (50 μM).

Conclusions: Because the location of L‐type calcium channels on soma and proximal dendrites gives these channels a crucial role in controlling dendritic excitability and in providing calcium for intracellular effectors, the decrease in the L‐type HVA Ca2+ currents may be an important anticonvulsant mechanism of TPM.
Topiramate as Add‐On Therapy: Pooled Analysis of Randomized Controlled Trials in Adults
Authors: Reife Ross , Pledger Gordon , Wu Shu‐Chen
Published: August 2005

Purpose: Six double‐blind, placebo‐controlled trials were conducted with topiramate (TPM) initiated as adjunctive therapy in adults with treatment‐resistant partial‐onset seizures with or without secondary generalization.

Methods: Because protocols and study populations were similar, data from the studies were pooled and analyzed for 527 patients treated with TPM and 216 treated with placebo.

Results: Seizures were reduced 50% in 43% of TPM‐treated patients and in 12% of placebo‐treated patients (p < 0·001); 5% of TPM‐treated patients, but no placebo‐treated patients, were seizure free during 11–19 weeks of double‐blind treatment (p < 0·001). The therapeutic effect was consistent regardless of seizure type, age, gender, baseline seizure rate, or concomitant antiepileptic drug (AED). With 100 mg/day TPM as a starting dosage and weekly dosage increments of 100–200 mg/day added to maximally tolerated dosages of AEDs, the most common treatment‐emergent adverse events (TEAEs) were dizziness, somnolence, fatigue, psychomotor slowing, nervousness, paresthesia, ataxia, memory difficulty and speech problems. These central nervous system effects were generally mild to moderate in severity, usually occurred early in treatment, often during titration, and resolved with continued treatment. Other notable TEAEs were weight loss and, in a small percentage of patients, renal calculi.
Effectiveness, Tolerability, and Safety of Topiramate in Children with Partial‐Onset Seizures
Authors: Ritter Frank , Glauser Tracy A. , Elterman Roy D. , Wyllie Elaine ,   the Topiramate YP Study Group
Published: August 2005

Purpose: Children with partial‐onset seizures, with or without secondary generalization, participating in a double‐blind, placebo‐controlled trial of topiramate (TPM) as adjunctive therapy were eligible to participate in an open‐label, long‐term extension study.

Methods: A total of 83 children (mean age, 9 years) continued long‐term open‐label TPM therapy in which the dosages of TPM and concomitant antiepileptic drugs (AEDs) were adjusted according to clinical response (mean TPM dosage, 9 mg/kg/day).

Results: Seizure frequency over the last 3 months of therapy was reduced ges;50% in 57% of children; 14% of children were seizure‐free ges;6 months at the last visit. During treatment periods up to 2 1/2 years (mean, 15 months), 6% of children discontinued because of treatment‐emergent adverse events; 13% discontinued because of inadequate seizure control.

Conclusions: From these findings, TPM is well tolerated and provides long‐term seizure control in children with partial‐onset seizures.
Long‐Term Response to Topiramate in Patients with West Syndrome
Authors: Glauser Tracy A. , Clark Peggy O. , McGee Kathy
Published: August 2005

Purpose: The long‐term effectiveness of topiramate (TPM) was evaluated in children with West syndrome previously refractory to antiepileptic drug (AED) therapy.

Methods: Children with infantile spasms who completed a pilot study were eligible to enter a long‐term extension phase in which the dosages of TPM and other AEDs could be adjusted to optimal response (maximum, 50 mg/kg/day TPM). The mean duration of long‐term therapy was 18 months in the 11 children who were followed; the mean TPM dosage was 29 mg/kg/day.

Results: Eight (73%) children were continuing TPM therapy at the time data were analyzed; four (50%) children were spasm free, seven (88%) had experienced a ges;50% reduction in spasms, and three (38%) were able to achieve TPM mono‐therapy.

Conclusions: TPM was well tolerated in that no patients discontinued because of adverse events. The response achieved with TPM during the pilot study was maintained in most children.
Increment of Synapsin I Protein in the Hippocampus of Kindled Rats
Authors: Suemaru Shuji , Sato Keiko , Sato Toshiki , Kodama Masazumi , Kitamura Yoshihiro , Koyama Fumihiko , Sato Soichiro , Ninomiya Yotaro , Morimoto Kiyoshi , Yamada Norihito , Kuroda Shigetoshi
Published: August 2005

Introduction: Synapsin is a vesiele‐associated protein considered to be involved in synaptogenesis and neurotransmitter release. Previously, we havc reported that synapsin I mRNA is significantly increased in the bilalcral dentate gyrus after amygdala‐kindled scizures. In this study, we investigated amygdala kindling‐induced changes i n synapsin I protein using immunohistochemistry. Quantitativc densitomctry (Mathern ct al., Ncurosciene, 1997) was performed to evaluatc changes i n synapsin I protein i n the hippocampus.

Method: Fifteen inale Sprague‐Dawley rats weighing 300–350 g wcre uscd. A tripolar elcctrode was implanted stcreotaxically in the hasolateral amygdala under pcntobarbital anesthesia. After a recovery period, the rats were subjected to daily kindling stimuli (a 2‐second train of 50 HL, I‐ins rectangular waves at a currcnt intensity of 75–250 PA). Animals with implanted electrodes without atimulation were used as controls (n = 7). They werc then pcrfused 8 hours aftcr the 24–32nd (average 293th) stage 4 or 5 (Racine's classification) generalized seiztirc under anesthesia. The brains were removed and placed in 4% paraloriiialdehyde for 2 days and then transferred to 15% sucrose dissolved in 0.1 M phosphate buffer (PB) for I week. They werc then quickly frozen with dry ice powder, and coronal scctions 20 +in thick wcrc cut with a cryostat. Immunohistochemistry was performcd with polyclonal synapsin I antibody (Calhiochem). The optical density of hippocampus staining was mcasured by a computer‐bascd image analyhtem as an average of the gray value, compensated by the original control sample between white (0) and black (255). Sections were imaged using a chat‐ged‐couplcd devicc camera attached to a microscope and captured and digitized using a Macintosh computer. Illuminance waa unformly maintained and checkcd after cvery I0 measurements using the original control samplc. The image was analysed using imaging software (NIH Image). Measurements were taken at the right and left hippocampus in >2 coronal sections for each animal.

Results and Discussion: The kindled slice exhibited bilatcrd increases i n synapsin I protein of approximately 20%–30% in the bilateral str. lucidurn of CA3, and by approximately 20%–40% in the bilateral dentate gyrus. In the hippocampus, neuronal plastic changes including sprouting have becn shown to develop as generalized kindled scizures are repeated. Therefore, the increased synapsin I protein in these brain regions may reilect the enhanced synaptic activity and the prcsynaptic plastic changes in the specific neural network of the hippocampus of kindled rats.
Regional Relationships Between Focal Abnormalities on SPECTs and High Power Zones on EEG Topographies of Background H Activities in Adult Patients with Partial Epilepsies
Authors: Jibiki Itsuki , Nakamura Mitsuhiko
Published: August 2005

Purpose: In previous studics regarding adult patients with partial epilepsies, we statistically found that the relativc power of 8 band with power spectral analysis of their hackground EEGs showed significant inverse correlation with absolute rCBF values with 123Tc‐HMPAO SPECT or the binding potential of benzodiaapinc receptors with 1211 ‐ iomazcnil SPECT, i n each cerebral region including epileptic foci or even in the whole cerebral regions. As ii series of study aiming at iuvcstigating the utility of SPECT scans for the clinic of epilepsy, we examined with visual inspection whether thcrc were regional relationships between EEG topographies of H hand i n the background EEGs and focal ahnormalitics on 123Tc‐HMPAO SPECT or 2I‐iomazenil SPECT i n adult patients with partial epilepsies.

Methods: Subjects were 27 adult epilcptic patients, composed of I4 mcn and I women, age range of 20–57 years old. Or the 27 patients, 6, 14, 2, and I patients had frontal, temporal, parietal, and occipital lobe epilepsies, respectively. The remaining 4 patients had u n tial epilepsies. Furthermore, 16 o l the 27 patients had intractable epilcpsics with seizure interval of days or weeks. All the subjects received 123Tc‐HMPAO SPECT and 99mI‐iomazenil SPECT scans and EEG examinations in the interictal periods, once an each within two weeks. MRI examinations were performed on 24 patients. EEG topographies of 0 band in background EEG activities were produced in the torm of 2‐dimensional brain mapping based on a quantitative analysis of the discontinuous monopolar recording of 24 sessions per EEG, each of which consisted of a continuous record of 5 second duration without artifacts or seizurc discharges.

Results: Epileptic foci on EEG were definitely dctcrmiiicd in 24 of the 27 patients, and 18 of the 24 patients (75.0%) showed a regional agrccment between the epileptic EEG foci and the highest or higher power zones in the topographies of H band in background EEG. Thirteen of the 27 patients showed focal abnormalities consisting of hypoperfusion images in 123Tc‐HMPAO SPECT scans. Eight of the 13 patients (6 I .5%) had a regional agreement between the hypoperfusion areas and the highest or higher 0 power m i e s in EEG topographies, whereas 9 of the 13 patients (69.2%) showed a regional agreement between the hypoperfusion areas and epilcptic EEG foci. 99m1‐ iomazenil SPECT scans revealed focal hypoaccumulation images i n 17 of thc 27 patients. Twelve of thc 17 patients (70.6%) showed a regional agreement between the hypoaccumulation areas and the highest or higher H power xones i n EEG topographies, although 10 of the 17 patients (58.8%1) had a regional agreement between the hypoaccumulation areas and epileptic EEG foci. In addition, MRI showed focal organic lesions in 9 of the 24 patients, and 4 of the 9 patients (44.4%J) showed a regional agreement between the lesions and the highest or higher 0 power zones in EEG topographies.
Delayed Reaction Time in Patients with Temporal Lobe Epilepsy.
Authors: Zheng Jiying , Okajima Hiroaki , Aikawa Hiroshi , Yamauchi Toshio
Published: August 2005

Purpose: Many reports have indicated that patients with temporal lobe epilepsy display a variety of cognitive impairments. The delay of reaction time is one of these impairments. However, it has been suggested that most of the tests used to measure cognitive function, such as reaction time, are influenced by motor speed. To clarify this ques‐ tion, we measured reaction times and carried out a Finger Tapping Test (FTT) in patients and controls, and differences in reaction time between these groups were analyzed after the motor speed component was removed. To avoid the influence of difference in stimulation and test difficulty, we measured 3 different reaction times. In addition, we investigated relationships between performance on these tasks and clinical characteristics to clarify factors related to these impairments.

Methods: The subjects were 21 patients with temporal lobe epilepsy (mean age 31.8 years: mean duration of illness 14.5 years) and 11 normal controls (mean age 31.2years). All patients had received AEDs. All subjects were examined by auditory simple reaction time, visual simple reaction time, visual choice reaction time, and FTT. Student's t test was applied to each variable across the 2 groups. Analysis of covariance was then applied, by which the variance in reaction times between the 2 groups that could be attributed to the most simple measure of motor speed (FTT) was factored out. Spearman's correlation analysis was applied to investigate relationships between performance on these tasks and clinical characteristics Resulrs: Performance on all 3 reaction times, including auditory simple reaction time (p<0.05), visual simple reaction time (p<O.O1), and visual choice reaction time (p<0.05), were longer in patients than controls. FTT yielded a significant (p<O.O1) inter‐group difference. When the variance in reaction times attributable to a simple measure of motor speed were factored out, differences in performance on visual simple reaction time (F=5.51, p<0.05) and in performance on visual choice reaction time (F=3.88, p<O.I) persisted. There was a significant positive correlation between performance on the FTT and seizure frequency (rs=O.48, p<0.05), as well as dosage of AEDs (rs= 0.65, p<O.Ol).

Conclusions: Our results suggest that the delayed reaction time in patients with temporal lobe epilepsy was not only due to reduction of motor speed but also due to impairment of other cognitive processes. It is generally accepted that many patients have some kind of cognitive impairments and many factors such as seizure, epileptic discharge, AEDs, and others may influence cognitive function. In present study it is indicated that delayed reaction time is due to several cognitive processes. Impairments of motor speed may have a relation to seizure frequency and dosage of AEDs. Several prior reports have indicated that some AEDs affect motor function. Our findings may reflect such a relationship.
A Case with Absence Seizures After Neuroimaging Changes of Rasmussen Syndrome
Authors: Yamanaka Erik , Noma Yurie , Ono Taeko , Yamada Keisuke , Takahashi Ryutarou , Miyake Susumu , Endo Shoichi
Published: August 2005

Case Report The patient was a 5 year and 5 month‐old boy. A brother had a history of febrile convulsions. The patient was born after 38 weeks of pregnancy, birth weight 3,260 g. The neonatal period was uneventful. His development was normal until 1 year and 3 months of age, after which he suffered generalized tonic seizures 2–3 times per year. Episodes of unconsciousness as often as ten times per day began at 5 years of age. Brain MRI, performed at 2 years of age, was normal. EEG revealed spikes from the right mid‐temporel and right central regions and diffuse irregular spike and waves at 4 years of age. Cryptogenic localization‐related epilepsy was diagnosed and treated with phenobarbital, carhamazepine, valproic acid, and acetazolamide without control of his convulsions. After 5 years of age, he began losing consciousness approximately 10 times per day. At 5 years and 5 months of age, he had fever, cough, rhinorrhea, and 2 generalized tonic‐clonic convulsions for about 2 minutes and subsequently generalized tonicclonic convulsive status epilepticus for 30 minutes. He was admitted to Kagawa Prefectural Central Hospital. At admission, his consciousness score was 200 points (JCS) and he had intermittent clonic convulsions of the right hand and face. He also exhibited right hemiplegia. Partial seizures continued for about 2 weeks, Blood examination revealed CRP of 1.4 mg/dl, with negative antibody titers for herpes simplex and EB virus. CSF findings were normal. At 6 days of admission, T2‐weighted brain MRI studies revealed high density i n the gray matter in the left hemisphere. After 2 months of hospitalization, MRI revealed remarkable left hemispheric atrophy. Two SPECT studies done at an interval of 2 months disclosed hyperperfusion of the left hemisphere. These findings were considered compatible with Rasmussen syndrome. At admission, the EEG revealed left high‐voltage slow wave activity and frequent spikes in the left anterior temporal region. After 4 months of hospitalization, tonic‐clonic convulsions occurred once per month. After 8 months of hospitalization, episodes of unconsciousness occurred 10 times per day. The ictal EEG revealed diffuse right hemisphere dominant 3isecond spike and wave bursts, which were induced by hyperventilation. Ethosuximide completely controlled these episodes and also improved EEG findings.

Conclusion: The clinical findings suggested that this patient had RdS‐ mussen syndrome during the course of a cryptogenic localizationrelated epilepsy and subsequently experienced absence seizures. Despite his organic brain damage, his ictal 3/second spike and wave bursts exhibited no preceding focal spikes or slow waves, and ethosuximide markedly improved these absence seizures and EEG abnormalities. The mechanism of these absence seizures was thus not secondary bilateral synchrony and appeared to be the same as that of the primary generalized seizures.
Examining the Impact of Interorganizational Systems on Process Efficiency and Sourcing Leverage in Buyer–Supplier Dyads
Authors: Saeed Khawaja A. , Malhotra Manoj K. , Grover Varun
Published: August 2005

Manufacturing firms are increasingly seeking cost and other competitive advantages by tightly coupling and managing their relationship with suppliers. Among other mechanisms, interorganizational systems (IOS) that facilitate boundary‐spanning activities of a firm enable them to effectively manage different types of buyer–supplier relationships. This study integrates literature from the operations and information systems fields to create a joint perspective in understanding the linkages between the nature of the IOS, buyer–supplier relationships, and manufacturing performance at the dyadic level. External integration, breadth, and initiation are used to capture IOS functionality, and their effect on process efficiency and sourcing leverage is examined. The study also explores the differences in how manufacturing firms use IOS when operating under varying levels of competitive intensity and product standardization. In order to test the research models and related hypothesis, empirical data on buyer–supplier dyads is collected from manufacturing firms. The results show that only higher levels of external integration that go beyond simple procurement systems, as well as who initiates the IOS, allow manufacturing firms to enhance process efficiency. In contrast, IOS breadth and IOS initiation enable manufacturing firms to enhance sourcing leverage over their suppliers. In addition, firms making standardized products in highly competitive environments tend to achieve higher process efficiencies and have higher levels of external integration. The study shows how specific IOS decisions allow manufacturing firms to better manage their dependence on the supplier for resources and thereby select system functionalities that are consistent with their own operating environments and the desired supply chain design.
An Enhanced Data Perturbation Approach for Small Data Sets
Authors: Muralidhar Krishnamurty , Sarathy Rathindra
Published: August 2005

As modern organizations gather, analyze, and share large quantities of data, issues of privacy, and confidentiality are becoming increasingly important. Perturbation methods are used to protect confidentiality when confidential, numerical data are shared or disseminated for analysis. Unfortunately, existing perturbation methods are not suitable for protecting small data sets. With small data sets, existing perturbation methods result in reduced protection against disclosure risk due to sampling error. Sampling error may also produce different results from the analysis of perturbed data compared to the original data, reducing data utility. In this study, we develop an enhancement of an existing perturbation technique, General Additive Data Perturbation, that can be used to effectively mask both large and small data sets. The proposed enhancement minimizes the risk of disclosure while ensuring that the results of commonly performed statistical analyses are identical and equal for both the original and the perturbed data.
Bone reactions to longstanding functional load at implants: an experimental study in dogs
Authors: Berglundh T. , Abrahamsson I. , Lindhe J.
Published: August 2005

Objectives: The aims of the present investigation were (i) to study marginal bone level alterations following implant installation, abutment connection and functional loading and (ii) to analyse bone tissue reactions to functional load.

Material and Methods: Six beagle dogs, about 1‐year old, were used. All mandibular pre‐molars were extracted. Three months later four implants of the Astra Tech Implants® Dental System were installed in one side of the mandible and four standard fixtures of the Brånemark System® were placed in the contralateral side of the mandible. Abutment connection was performed 3 months later and a plaque control programme was initiated. Three months after abutment connection fixed partial dentures (FPDs) made in gold were cemented to the maxillary canines and pre‐molars. FPDs were also connected to the three posterior implants in each side of the mandible, while the mesial implant in each side was used as an unloaded control. Radiographs were obtained from all implant sites following implant installation, abutment connection and FPD placement. Ten months after the FPD placement the radiographic examination was repeated. The animals were sacrificed and biopsies from all implant sites were obtained and prepared for histological analysis.

Results: The radiographic analysis revealed that largest amount of bone loss occurred following implant installation and abutment connection and that this loss was more pronounced at Brånemark than at Astra implants. The bone level alterations that were observed at implants exposed to 10 months of functional load in both implant systems were small and did not differ from control sites. The histological analysis revealed that implants exposed to functional load exhibited a higher degree of bone‐to‐implant contact than control implants in both implant systems.

Conclusion: It is suggested that functional load at implants may enhance osseointegration and does not result in marginal bone loss.
Analysis of rat calvaria defects implanted with a platelet‐rich plasma preparation: histologic and histometric observations
Authors: Pryor Mary E. , Polimeni Giuseppe , Koo Ki‐Tae , Hartman Michael J. , Gross Howard , April Milton , Safadi Fayez F. , Wikesjö Ulf M. E.
Published: August 2005

Objectives: It has been suggested that degranulating platelet α‐granules release growth factors having a potential to modulate bone formation. The objective of this study was to evaluate the osteoconductive potential of a platelet‐rich plasma (PRP) preparation.

Methods: Thirty adult male Sprague–Dawley rats were used. The PRP preparation was obtained from 10 ml of whole blood drawn from one age‐matched donor rat. The preparation was processed by gradient density centrifugation and stored at −80°C until use. Using aseptic techniques, the PRP preparation soak loaded onto an absorbable collagen sponge (ACS) or ACS alone was surgically implanted into contralateral critical size 6‐mm calvaria osteotomies in 18 animals. Twelve animals received ACS versus sham surgery in contralateral defects. Animals were sacrificed at 4 and 8 weeks when biopsies were collected for histologic and histometric analysis.

Results: The animals were maintained without adverse events. Bone formation was highly variable in sites receiving PRP and control treatments. Defect bone fill at 4 weeks averaged (±SD) 28.8±27.4% (PRP/ACS) versus 39.1±24.4% (ACS; p=0.2626) and 62.0±20.0% (ACS) versus 71.6±32.2% (sham surgery; p=0.1088), and at 8 weeks 81.0±12.9% (PRP/ACS) versus 64.5±28.1% (ACS; p=0.2626) and 75.6±34.1% (ACS) versus 74.1±24.2% (sham surgery; p=0.7353). Remnants of the ACS biomaterial were observed at both 4 and 8 weeks in sites implanted with PRP/ACS or ACS.

Conclusions: The results suggest that the PRP preparation has a limited potential to promote local bone formation.
Autogenous bone chips: influence of a new piezoelectric device (Piezosurgery®) on chip morphology, cell viability and differentiation
Authors: Chiriac G. , Herten M. , Schwarz F. , Rothamel D. , Becker J.
Published: August 2005

Aim: The aim of the present study was to investigate the influence of a new piezoelectric device, designed for harvesting autogenous bone chips from intra‐oral sites, on chip morphology, cell viability and differentiation.

Methods: A total of 69 samples of cortical bone chips were randomly gained by either (1) a piezoelectric device (PS), or (2) conventional rotating drills (RD). Shape and size of the bone chips were compared by means of morphometrical analysis. Outgrowing osteoblasts were identified by means of alkaline phosphatase activity (AP), immunhistochemical staining for osteocalcin (OC) synthesis and reverse transcriptase‐polymerase chain reaction phenotyping.

Results: In 88.9% of the RD and 87.9% of the PS specimens, an outgrowth of adherent cells nearby the bone chips was observed after 6–19 days. Confluence of cells was reached after 4 weeks. Positive staining for AP and OC identified the cells as osteoblasts. The morphometrical analysis revealed a statistically significant more voluminous size of the particles collected with PS than RD.

Conclusion: Within the limits of the present study, it may be concluded that both the harvesting methods are not different from each other concerning their detrimental effect on viability and differentiation of cells growing out of autogenous bone chips derived from intra‐oral cortical sites.
Open flap debridement with or without intentional cementum removal: a 4‐month follow‐up
Authors: Wilson Sallum Antonio , Vasconcelos Alves Renato , Flávio Teixeira Damis Lúcio , Fernanda Roesler Bertolini Patricia , Humberto Nociti Francisco , Antonio Sallum Enilson
Published: August 2005

Objectives: The aim of this study was to investigate the influence of cementum removal on periodontal repair.

Material and Methods: Forty subjects with chronic periodontitis and presenting, at least, two proximal sites in anterior teeth (upper or lower) with probing depth 5 mm were selected. After oral hygiene instructions and ultrasonic supragingival instrumentation, the subjects were randomly assigned for one of the following groups: CIC, scaled with Gracey curettes; CIUS, scaled with ultrasonic device; CDC, calculus deattachment with Gracey curettes and brushing with saline solution; and CDUS, calculus deattachment with ultrasonic device and brushing with saline solution. Full‐thickness flaps were reflected and the instrumentation was performed with a clinical microscope. Probing depth (PD), relative gingival margin level (RGML) and relative attachment level (RAL) were registered at five experimental periods: baseline and 30, 60, 90 and 120 days postoperative.

Results: All the approaches were able to markedly reduce the PD values from the baseline to the other evaluation periods (p<0.0001). The increase in RGML values was statistically significant only for the CDUS group. There were no statistically significant differences between the baseline and postoperative values in all groups for the RAL changes. The changes in RAL were statistically significant only among the groups CDC and CDUS (p<0.0001).

Conclusion: The conventional scaling and root planing and the calculus deattachment were effective in reducing the probing depth values, regardless of the instrumentation method.
Effects of phase I periodontal treatment on gingival crevicular fluid levels of matrix metalloproteinase‐3 and tissue inhibitor of metalloproteinase‐1
Authors: Tüter Gülay , Kurtiş Bülent , Serdar Muhittin , Yücel Ayşegül , Ayhan Eylem , Karaduman Burcu , Özcan Gönen
Published: August 2005

Objectives: The aim of this study was to evaluate the effects of phase I periodontal treatment on gingival crevicular fluid (GCF) levels of matrix metalloproteinase (MMP)‐3 and tissue inhibitors of metalloproteinase (TIMP)‐1.

Methods: Plaque index, gingival index, pocket depth and clinical attachment loss were recorded and GCF samples were collected from 20 chronic periodontitis (CP) patients and 20 periodontally healthy controls (C) before treatment. CP patients received phase I periodontal treatment and all clinical parameters were recorded and GCF samples were collected once more after treatment. Assays were performed by an enzyme‐linked immunosorbent assay.

Results: All of the clinical parameters improved significantly after the therapy (p<0.05). Baseline GCF levels of MMP‐3 were significantly higher than C and that level was reduced significantly by treatment compared with baseline levels (p<0.05). Baseline GCF levels of TIMP‐1 were lower than post‐treatment levels and C (p<0.05). GCF levels of TIMP‐1 increased significantly by treatment compared with baseline levels (p<0.05).

Conclusion: This study shows that the clinical improvements after phase I periodontal therapy are accompanied by reduction in MMP‐3 and increasing in TIMP‐1 GCF levels.
WATER‐ABSORPTION CHARACTERISTICS OF VARIOUS PEARL MILLET CULTIVARS AND SORGHUM GROWN IN NORTHERN NIGERIA
Authors: BADAU M.H. , NKAMA I. , JIDEANI I.A.
Published: August 2005

Ten pearl millet cultivars and one sorghum cultivar were evaluated for physical properties and chemical composition. Water‐absorption characteristics of these grains were also determined using Peleg's equation. Results indicated wide variations in thousand‐kernel weight and volume, grain hardness, percent floaters, in addition to considerable variations in protein, fat and crude fiber. Peleg's equation gave a reasonable fit to experimental data. Peleg constants K1 were obtained for the pearl millet cultivars. Temperature dependence of the reciprocal of the Peleg constant K1 was determined using an Arrhenius equation. Activation energies were in the range of 1.405–6.572 kJ/mol. A linear relationship was proposed to describe the relationship between the rate of absorbed water per unit change in temperature and activation energy.
Design of Multimaterial Compliant Mechanisms Using Level-Set Methods
Authors: Wang Michael Yu , Chen Shikui , Wang Xiaoming , Mei Yulin
Published: August 2005

A monolithic compliant mechanism transmits applied forces from specified input ports to output ports by elastic deformation of its comprising materials, fulfilling required functions analogous to a rigid-body mechanism. In this paper, we propose a level-set method for designing monolithic compliant mechanisms made of multiple materials as an optimization of continuum heterogeneous structures. Central to the method is a multiphase level-set model that precisely specifies the distinct material regions and their sharp interfaces as well as the geometric boundary of the structure. Combined with the classical shape derivatives, the level-set method yields an Eulerian computational system of geometric partial differential equations, capable of performing topological changes and capturing geometric evolutions at the interface and the boundary. The proposed method is demonstrated for single-input and single-output mechanisms and illustrated with several two-dimensional examples of synthesis of multimaterial mechanisms of force inverters and gripping and clamping devices. An analysis on the formation of de facto hinges is presented based on the shape gradient information. A scheme to ensure a well-connected topology of the mechanism during the process of optimization is also presented.