bluuebunny/crossref_metadata_2025 huggingface dataset:
Resistance to Propagation of Amygdaloid Kindling Seizures in Rats with Genetic Absence Epilepsy
Authors: Eşkazan Esat , Onat Filiz Yõlmaz , Aker Rezzan , Öner Gülay
Published: March 2003

Summary:  Purpose: The existence of absence epilepsy and temporal partial seizure pattern in the same patient is an uncommon state. In the present study, we aimed to evaluate whether the process of kindling as a model of complex partial seizures with secondary generalization is altered in rats with genetic absence epilepsy.

Methods: Six‐ to 12‐month‐old nonepileptic control Wistar rats and genetic absence epileptic rats from Strasbourg (GAERS) were used in the experiments. One week before the experiments, bilateral stimulation and recording electrodes were implanted stereotaxically into the basolateral amygdala and cortex, respectively. Animals were stimulated at their afterdischarge threshold current twice daily for the process of kindling and accepted as fully kindled after the occurrence of five grade 5 seizures. Bilateral EEGs from amygdala and cortex were recorded continuously during 20 min before and 40 min after each stimulus.

Results: All control Wistar rats were fully kindled after stimulus 12 to 15. Although the maximal number of stimulations had been applied, GAERS remained at stage 2, and no motor seizures were observed. The afterdischarge duration in bilateral amygdala and the cortex after the kindling stimulus was shorter in GAERS when compared with control rats.

Conclusions: Occurrence of only grade 2 seizures and no observation of grade 3–5 seizures in GAERS with the maximal number of stimulations would suggest that the generalized absence seizures may be the reason of the resistance in the secondary generalization of limbic seizures during amygdala kindling.
Topiramate and Metabolic Acidosis in Infants and Toddlers
Authors: Philippi Heike , Boor Rainer , Reitter Bernd
Published: March 2003

Summary:  Purpose: Topiramate (TPM) inhibits carbonic anhydrase, with metabolic acidosis as a possible side effect, although this has been reported in only two adult cases. We investigated the acid–base metabolism in infants and toddlers treated with TPM.

Methods: Nine infants and toddlers aged 5 months to 2.3 years (median, 6 months) were treated with TPM at maximal doses of 8.2–26 mg/kg/day (median, 11 mg/kg/day). The maximal TPM dose was achieved after 8–35 days (median, 17 days). TPM was given in addition to other antiepileptic drugs (AEDs) in five cases and as a sole AED in four patients with refractory epilepsy resistant to multiple AEDs. The diagnoses were infantile spasms (n = 5), epilepsia partialis continua (n = 1), infantile epileptic encephalopathy (n = 1), and Lennox–Gastaut syndrome (n = 2).

Results: The blood gases were normal before treatment with TPM in all nine children. Metabolic acidosis developed in eight children after 8–26 days (median, 14 days) of TPM treatment with a minimum of serum bicarbonate between 15 to 18 mM (median, 17 mM), a minimal base excess between –6.2 and –11.2 mM (median, –7.9 mM), and pH between 7.22 and 7.40 (median, 7.35). Four of nine children showed clinical signs of hyperventilation and received oral sodium bicarbonate (1–2 mmol/kg), while TPM was still effective.

Conclusions: Because metabolic acidosis developed in eight of the nine infants and toddlers taking TPM, we would suggest that the acid–base metabolism be monitored in young children who receive TPM.
Epilepsy and Mortality: A Record Linkage Study in a U.K. Population
Authors: Morgan Christopher Ll. , Kerr Michael P.
Published: March 2003

Summary: Purpose:To examine patterns of mortality for a population with epilepsy compared with the nonepilepsy population.

Methods:The study used cross‐sectional record linkage, combining an electronic death register with an epilepsy patient register constructed from a variety of routine health data sources collected from 1991 to 1997. The study was conducted in Cardiff and the Vale of Glamorgan, Wales, U.K., and included all deaths recorded between 1993 and 1996.

Results:There were 352 deaths for patients with epilepsy, 2.0% of all deaths. The crude mortality rates for patients with and without epilepsy were 36.2 and 9.9 per 1,000. The Standardised Mortality Ratio was 2.14 (95% CI, 1.74–2.55) for 1996 deaths. The single most common disease group was cancer, accounting for 66 (18.8%) of deaths for people with epilepsy (SMR, 1.47; 95% CI, 1.11–1.82). Significant excesses were demonstrated for cerebrovascular disease, diseases of the digestive system, respiratory diseases, and other causes of death.

Conclusions:People with epilepsy have an increased mortality over the population as a whole. The main causes of death are those most common in the population as a whole and those that underlie the epilepsy itself.
Increased Excitability and Decreased Sensitivity to GABA in an Animal Model of Dysplastic Cortex
Authors: Benardete Ethan A. , Kriegstein Arnold R.
Published: March 2003

Summary: Purpose:Cortical dysplasia (CD) is associated with epilepsy in both the pediatric and adult populations. The mechanism underlying seizures with cortical malformations is still poorly understood. To study the physiology of dysplastic cortex, we developed an experimental model of CD.

Methods:Pregnant rats were given intraperitoneal injections of carmustine (1‐3‐bis‐chloroethyl‐nitrosourea; BCNU) on embryonic day 15 (E15). Cortical histology was examined in the resulting pups at P0, P28, and P60. In addition, evoked and spontaneous field potential recordings were obtained in cortical slices from adult control and BCNU‐exposed rats. Finally, we used whole‐cell recordings to compare physiologic properties of pyramidal neurons and γ‐aminobutyric acid (GABA) responses in control and BCNU‐treated animals.

Results:Features characteristic of CD were found in the offspring, including laminar disorganization, cytomegalic neurons, and neuronal heterotopias. Dysplastic cortex also contained abnormal clusters of Cajal–Retzius (CR) cells and disruption of radial glial fibers, as demonstrated with immunohistochemistry. Under conditions of partial GABAA‐receptor blockade with 10 μMbicuculline methiodide (BMI), slices of dysplastic cortex demonstrated a significant increase in the number of spontaneous and evoked epileptiform discharges. Individual pyramidal neurons in dysplastic cortex were less sensitive to application of GABA compared with controls.

Conclusions:BCNU exposure in utero produces histologic alterations suggestive of CD in rat offspring. Dysplastic cortex from this model demonstrates features of hyperexcitability and decreased neuronal sensitivity to GABA. Such physiologic alterations may underlie the increased epileptogenicity of dysplastic cortex.
Influence on Ictal Seizure Semiology of Rapid Withdrawal of Carbamazepine and Valproate in Monotherapy
Authors: Zhou Dong , Wang Ying , Hopp Peter , Kerling Frank , Kirchner Annette , Pauli Elisabeth , Stefan Hermann
Published: March 2003

Summary:  Purpose: To quantify changes in ictal seizure semiology during rapid withdrawal of carbamazepine (CBZ) and valproate (VPA) from a monoregimen in presurgical evaluation.

Methods: Therapeutic intensive seizure analysis (TISA) with video‐EEG monitoring was used in 33 patients with pharmacoresistant partial epilepsy undergoing complete withdrawal of CBZ (20 patients) or VPA (13 patients) from a monoregimen. Monitoring phases included a 3‐day baseline phase, a 3‐day rapid antiepileptic drug (AED) withdrawal phase, and another 3‐day AED‐free phase with AEDs in subtherapeutic levels. Seizure variables as complete processes and their various elements (ictal signs) were analyzed, including duration (seconds), intensity (on a scale of 0 to 3), frequency (number per 3 days), and total duration of seizures and ictal signs in 3 days (seconds). The localization of seizure patterns on ictal EEG recording (EEG seizure onset) and the first appearing clinical ictal phenomena (initial ictal signs) were recorded.

Results: A total of 188 seizures in the CBZ group and 57 seizures in the VPA group were investigated. Compared with the baseline phase, the CBZ group showed increases in duration, frequency of seizures, various ictal signs, and secondarily generalized tonic and clonic signs during the following two phases. Significantly increased values of the VPA group were observed in seizure duration and frequency of hypermotoric phenomena during the AED‐free phase. More patients in the CBZ group had secondarily generalized clonic signs during the AED‐free phase. EEG seizure onset and initial ictal signs showed no obvious changes between study phases.

Conclusions: Withdrawal of CBZ is followed more quickly by an increase of seizure frequency and severity than is the case for VPA withdrawal. Both CBZ and VPA withdrawal influences seizure propagation rather than the seizure‐onset characteristics, which speaks in favor of its use in presurgical evaluation.
Benign Epilepsy with Centro‐temporal Spikes: Spike Triggered fMRI Shows Somato‐sensory Cortex Activity
Authors: Archer John S. , Briellman Regula S. , Abbott David F. , Syngeniotis Ari , Wellard R. Mark , Jackson Graeme D.
Published: March 2003

Summary:  Objective: We performed spike triggered functional MRI (fMRI) in a 12 year old girl with Benign Epilepsy with Centro‐temporal Spikes (BECTS) and left‐sided spikes. Our aim was to demonstrate the cerebral origin of her interictal spikes.

Methods: EEG was recorded within the 3 Tesla MRI. Whole brain fMRI images were acquired, beginning 2–3 seconds after spikes. Baseline fMRI images were acquired when there were no spikes for 20 seconds. Image sets were compared with the Student's t‐test.

Results: Ten spike and 20 baseline brain volumes were analysed. Focal activiation was seen in the inferior left sensorimotor cortex near the face area. The anterior cingulate was more active during baseline than spikes.

Conclusions: Left sided epileptiform activity in this patient with BECTS is associated with fMRI activation in the left face region of the somatosensory cortex, which would be consistent with the facial sensorimotor involvement in BECT seizures. The presence of BOLD signal change in other regions raises the possibility that the scalp recorded field of this patient with BECTs may reflect electrical change in more than one brain region.
Differential Expression of GABA and Glutamate‐receptor Subunits and Enzymes Involved in GABA Metabolism between Electrophysiologically Identified Hippocampal CA1 Pyramidal Cells and Interneurons
Authors: Telfeian Albert E. , Tseng Henry C. , Baybis Marianna , Crino Peter B. , Dichter Marc A.
Published: March 2003

Summary:  Purpose: The balance between synaptic excitation and inhibition within the hippocampus is critical for maintaining normal hippocampal function. Even mild reduction in inhibition or enhancement of excitation can produce seizures. Synaptic excitation is produced by pyramidal cells and granule cells, whereas inhibition is produced by a smaller number of interneurons. To understand how two subpopulations of these excitatory and inhibitory neurons are regulated at the molecular level, we analyzed specific mRNA expression profiles for receptors that are significantly involved in synaptic transmission and in the synthesis and storage of the principal inhibitory neurotransmitter, γ‐aminobutyric acid (GABA). Our hypothesis was that differences in gene expression between inhibitory and excitatory neurons in the rat hippocampus might point to specific new targets for seizure pharmacotherapy.

Methods: We combined the techniques of (a) whole‐cell patch clamping in rat hippocampal slices, (b) biocytin staining for cell identification, (c) single‐cell mRNA amplification, and (d) small‐scale cDNA microarray analysis to allow us to obtain expression profiles for candidate genes from identified CA1 pyramidal neurons and interneurons. Electrophysiologic and morphologic data and expression profiles were obtained from 12 stratum pyramidale and seven stratum radiatum cells.

Results: Presumed inhibitory neurons expressed significantly more GAD65, GAD67, vGAT, GABAA‐receptor α3, and N‐methyl‐d‐aspartate (NMDA)‐receptor IIB mRNA, and presumed excitatory neurons expressed more GABAA‐receptor α1, and NMDA‐receptor I mRNA.

Conclusions: Differential expression of candidate neurotransmitter‐receptor subunits distinguished CA1 pyramidal neurons from interneurons. These differences may indicate potential new targets for altering the balance of inhibition and excitation in the treatment of epilepsy.
Mesial Temporal Sclerosis in Acute Childhood Leukemias
Authors: Goyal Monisha , Bangert Barbara A. , Wiznitzer Max
Published: March 2003

Summary:  Purpose: Although seizures are relatively common in acute childhood leukemias, evolution into epilepsy is rare.

Methods: We describe three patients with acute leukemias who received chemotherapy. One patient also received cranial irradiation.

Results: All three developed recurrent complex partial seizures after initiation of chemotherapy. Initial neuroimaging performed in two patients was normal. Subsequent neuroimaging in all three revealed mesial temporal sclerosis.

Conclusions: The association of mesial temporal sclerosis in acute childhood leukemias has not been previously described and may be secondary to antileukemic treatment and recurrent seizures.
Lateralising Value of Neuropsychological Protocols for Presurgical Assessment of Temporal Lobe Epilepsy
Authors: Akanuma Nozomi , Alarcón Gonzalo , Lum Francis , Kissani Najib , Koutroumanidis Michael , Adachi Naoto , Binnie Colin D. , Polkey Charles E. , Morris Robin G.
Published: March 2003

Summary:  Purpose: To estimate the value of neuropsychological measurements in determining the side of seizure onset for presurgical assessment in patients with temporal lobe epilepsy. The lateralising value of neuropsychological protocols was evaluated for all patients and in subpopulations depending on surgical outcome with regard to seizure control, speech dominance, neuropathology, and need for intracranial EEG recordings.

Methods: A battery of neuropsychological procedures was carried out preoperatively in 125 patients who underwent left (n = 66) or right (n = 59) temporal lobectomies. Binary logistic regression analysis was performed to find sets of variables that allowed the best prediction of the side of seizure onset (assumed to be the operated‐on side).

Results: Combinations of noninvasive neuropsychological tests and Wada subscores showed the highest lateralising values: 80.8% for all patients, 79.4% in seizure‐free patients, 86.0% in patients not rendered seizure free, 85.7% in left speech patients, 77.8% in non–left speech patients, 89.3% in patients with mesial temporal sclerosis (MTS), 78.1% in non‐MTS patients, 80.3% in patients who underwent intracranial EEG recordings, and 77.3% in those who did not.

Conclusions: The lateralising value (80‐90%) of neuropsychological protocols appears similar to that of other tests widely accepted for lateralisation (ictal and interictal scalp EEG and neuroimaging). Attention should be paid to neuropsychological results, particularly from the Wada test, during presurgical assessment of temporal lobe epilepsy, as they can provide strong support for findings from other lateralising tests, particularly in patients with presumed MTS or in left‐speech patients.
Bilateral Rasmussen Encephalitis: Postmortem Documentation in a Five‐year‐old
Authors: Tobias Sharon M. , Robitaille Yves , Hickey William F. , Rhodes C. Harker , Nordgren Richard , Andermann Frederick
Published: March 2003

Summary: A case of Rasmussen encephalitis with bilateral involvement and onset at age 2 years is reviewed. Rasmussen encephalitis is a rare progressive disease that causes intractable seizures, cognitive decline, and inflammatory changes in the brain. The neurologic involvement is characteristically unilateral. Bilateral involvement in this case was suspected within 5 months of presentation and was confirmed by bilateral frontal lobe biopsies. The severity and progression of the disease in this case was remarkable and resulted in the patient's death by age 5 years, despite numerous attempted therapeutic interventions. Autopsy findings confirmed the diagnosis of Rasmussen encephalitis with bilateral involvement.
Is It Status?
Authors: Brenner Richard P.
Published: March 2003

Summary: Nonconvulsive status epilepticus (NCSE) is difficult to diagnose in the obtunded/comatose patient. Such patients often have other serious medical conditions, and the diagnosis is frequently delayed. We review criteria for diagnosis, treatment, and prognosis of NCSE in this setting. Terms that have been used to describe SE in obtunded/comatose patients without tonic–clonic convulsions include subtle generalized SE, electrographic SE, SE in comatose patients, generalized electrographic SE, non–tonic–clonic SE, subclinical SE, and NCSE. Sometimes the same term has been used when describing different disorders, and different terms are often applied for the same entity. The incidence of NCSE in obtunded/comatose patients is uncertain. Clinically they may display subtle, intermittent focal or multifocal rhythmic movements suggestive of seizures; there may not be movements. NCSE can occur in a variety of disorders, including hypoxia, metabolic disturbances, and after convulsive seizures. A number of EEG patterns have been described in NCSE, and many of these are controversial, particularly as to whether they are ictal. These include periodic lateralized epileptiform discharges (PLEDS), bilateral independent PLEDS (BIPLEDS), periodic epileptiform discharges (PEDS), which can be either focal or generalized, and generalized triphasic waves (TWs). The diagnostic criteria for NCSE also are controversial, and there are no agreed‐on criteria to diagnose NCSE in obtunded/comatose patients, nor is there consensus on how it should it be treated. Furthermore, outcome is poor, and several studies suggest that treatment may not be helpful.
Epileptogenesis After Self‐Sustaining Status Epilepticus
Authors: Mazarati Andrey , Bragin Anatol , Baldwin Roger , Shin Don , Wilson Charles , Sankar Raman , Naylor David , Engel Jerome , Wasterlain Claude G.
Published: March 2003

Summary:  Purpose: To describe the natural history of chronic epilepsy after experimental self‐sustaining status epilepticus (SSSE) and to correlate patterns of SSSE with ictal, interictal, and plastic changes that characterize chronic epilepsy.

Methods: SSSE was induced in adult Wistar rats by 30‐min intermittent electrical stimulation of the perforant path. In some animals, SSSE was treated by short‐term administration of antiepileptic drugs (AEDs). After SSSE, EEG and animal behavior were monitored for ≤1 year. Some animals were killed to study mossy fiber sprouting in the dentate gyrus.

Results: Despite the high reproducibility of the electrographic and behavioral manifestations of SSSE, patterns of chronic epilepsy varied considerably among animals in terms of seizure frequency, initial seizure pattern at the onset of chronic epilepsy, and frequency of interictal spikes. Statistically significant correlations were found between spike frequency during SSSE and interictal spike frequency, as well as between the frequency of spontaneous seizures and degree of mossy fiber sprouting. Early treatment of SSSE prevented the occurrence of spontaneous seizures and significantly decreased frequency of interictal spikes. Late treatment of SSSE did not prevent spontaneous seizures, but significantly decreased their frequency, and eventually may lead to remission of epilepsy.

Conclusions: SSSE leads after a “silent” period to chronic epilepsy, which is maintained for ≥1 year in the rat. The silence is only behavioral, because EEG paroxysmal activity is seen in every animal. In this model of SSSE, the timing of treatment is a major determinant of outcome. Early treatment reduces the incidence of chronic epilepsy, whereas late treatment only reduces its severity. The possibility that this reduction of the severity of epilepsy may led to spontaneous remissions merits further study.
Seizures Decrease Postnatal Neurogenesis and Granule Cell Development in the Human Fascia tDentata
Authors: Mathern Gary W. , Leiphart James L. , De Vera Adelaine , Adelson P. David , Seki Tatsunori , Neder Luciano , Leite Joao P.
Published: March 2003

Summary:  Purpose: There is considerable controversy whether childhood seizures damage existing neurons and/or adversely affect neurogenesis and synaptogenesis. This study addressed this question by examining fascia dentata neurogenesis, cell death, and aberrant axon connections in hippocampi from children with extratemporal seizure foci.

Methods: Surgically resected (n = 53) and age‐comparable autopsy (n = 22) hippocampi were studied for neuronal densities, polysialic acid (PSA) neural cell adhesion molecule (NCAM) immunoreactivity (IR), TUNEL, and neo‐Timm's histochemistry.

Results: Compared with autopsy cases, hippocampi from children with frequent seizures showed (a) decreased fascia dentata granule cell densities; (b) decreased PSA NCAM IR cell densities in the stratum granulosum, infragranular, and hilar regions; (c) no positive TUNEL‐stained cells; and (d) aberrant supragranular mossy fiber axon connections.

Conclusions: These results indicate that severe seizures during early childhood are associated with anatomic signs of decreased postnatal granule cell neurogenesis (PSA NCAM IR) and aberrant mossy fiber axon connections (neo‐Timm's) without evidence of seizure‐induced cell death (TUNEL). In humans, these results support the concept that seizures do not damage existing neurons, but adversely affect processes involved with normal postnatal neuronal development such as neurogenesis and axon formation. Such alterations probably negatively affect normal brain development, and/or promote epileptogenesis.
Estrogen Treatment Protects GABAB Inhibition in the Dentate Gyrus of Female Rats after Kainic Acid–Induced Status Epilepticus
Authors: Velíšek Libor , Velíšková Jana
Published: March 2003

Summary:  Purpose: We used the paired‐pulse inhibition paradigm to determine whether the cell loss in the hilus of the dentate gyrus of female rats after kainic acid (KA)‐induced status epilepticus (SE) is associated with functional changes in the dentate gyrus. Additionally, we determined whether the lost function could be preserved by using estrogen neuroprotection.

Methods: Female rats were ovariectomized and treated either with estrogen replacement (four doses of 2 μg of estradiol every 24 h: two doses before SE, two doses after) or oil. SE was induced by I.P. administration of KA (16 mg/kg) and terminated after 5 h with pentobarbital. After 2 days, hippocampal/dentate gyrus slices were prepared. Population spikes were recorded in the granule cell layer as a response to mixed perforant‐path stimulation (10‐ to 1,000‐ms interstimulus intervals). Ratios of the test response to conditioning response were evaluated. γ‐Aminobutyric acid type B (GABAB) receptors were blocked with 400 μM CGP 35348.

Results: In slices from oil‐treated rats, SE induced a loss of paired‐pulse inhibition in the dentate gyrus at the interstimulus intervals marking intermediate facilitation and late depression. There was no such loss of paired‐pulse inhibition in estrogen‐treated rats. CGP 35348 was unable to alter paired‐pulse inhibition in slices form oil‐treated rats. In slices from estrogen‐treated rats, CGP decreased paired‐pulse inhibition at 50–150‐ms interstimulus intervals. Comparison of paired‐pulse inhibition in slices from oil‐treated rats with slices from estrogen‐treated rats with CGP 35348 revealed a GABAB‐independent difference at interstimulus intervals >300 ms.

Conclusions: Our study demonstrated that there is a complete loss of GABAB receptor–mediated inhibition after KA‐induced SE in the dentate gyrus. Pretreatment with estrogen can save GABAB‐receptor function, probably by neuroprotection of neurons containing the postsynaptic GABAB receptors.
Extracellular Matrix Components are Altered in the Hippocampus, Cortex, and Cerebrospinal Fluid of Patients with Mesial Temporal Lobe Epilepsy
Authors: Perosa S. R. , Porcionatto M. A. , Cukiert A. , Martins J. R. M. , Amado D. , Nader H. B. , Cavalheiro E. A. , Leite J. P. , Naffah‐Mazzacoratti M. G.
Published: March 2003

Summary:  Purpose: This work studied the profile of glycosaminoglycans (GAGs) in the hippocampus, cortex, and cerebrospinal fluid of patients with temporal lobe epilepsy (TLE).

Methods: The GAGs were analyzed by agarose gel electrophoresis, enzymatic degradation, and enzyme‐linked immunosorbent assay (ELISA).

Results: The hippocampus of TLE patients showed increased levels of chondroitin sulfate and hyaluronic acid against normal levels of these GAGs in the neocortex and cerebrospinal fluid (CSF).

Conclusions: These results suggest that these matrix components could be involved in the pathophysiology of TLE.
Determinants of Ictal Epileptiform Patterns in the Hippocampal Slice
Authors: Rutecki Paul A. , Sayin Umit , Yang Yili , Hadar Eldad
Published: March 2003

Summary:  Purpose: The transition from an interictal to an ictal pattern of epileptiform activity is a strategic target for antiepileptic drug (AED) action. Both the muscarinic agonist pilocarpine and the selective group I metabotropic glutamate receptor (mGluR) agonist (RS)‐3,5‐dihydroxyphenylglycine (DHPG) produce prolonged synchronous activity in the hippocampal slice that resembles ictal discharges. We evaluated the role of synaptic mechanisms and release of calcium from intracellular stores in the generation of prolonged ictal oscillations.

Methods: Pilocarpine (10 μM) in 7.5 mM[K+]o or DHPG (100 μM) in 5 mM[K+]o artificial cerebrospinal fluid (ACSF) were bath applied to hippocampal slices, and extracellular recordings were made from the CA3 region. The pattern of activity was characterized as ictal if prolonged oscillations of discharges occurred at >2 Hz lasting for >3 s. The pattern of epileptiform activity was characterized and compared with the pattern observed after bath application of pharmacologic agents.

Results: The AMPA/kainic acid (KA) glutamate receptor blocker DNQX (20 μM) dampened and stopped ictal oscillations; however, antagonism of N‐methyl‐d‐aspartate (NMDA) or γ‐aminobutyric acid (GABAA) receptors had minimal effects on ictal patterns. Ictal discharges were suppressed by dantrolene (30–100 μM), which blocks release of calcium from intracellular stores, or thapsigargin (1–5 μM), which inhibits the adenosine triphosphatase (ATPase) that maintains intracellular calcium stores. The L‐type calcium channel antagonist nifedipine (1 μM) blocked ictal activity produced by pilocarpine or DHPG.

Conclusions: Ictal discharges produced by pilocarpine or DHPG depended on intact synaptic transmission mediated by AMPA/KA receptors, release of calcium from intracellular stores, and L‐type calcium channel activation. The results suggest that muscarinic and group I mGluRs activate a positive‐feedback system that creates calcium oscillations and prolonged neuronal synchronization mediated by recurrent excitatory synaptic connections in the CA3 region of the hippocampus.
Involvement of the Neuropeptide Orphanin FQ/Nociceptin in Kainate and Kindling Seizures and Epileptogenesis
Authors: Bregola G. , Zucchini S. , Frigati L. , Candeletti S. , Romualdi P. , Reinscheid R. , Simonato M.
Published: March 2003

Summary:  Purpose: To investigate the role of orphanin FQ/nociceptin (OFQ/N) in epilepsy, we analyzed (a) proOFQ/N (the OFQ/N precursor) and ORL‐1 (the OFQ/N receptor) messenger RNA (mRNA) levels in the kainate and in the kindling models of epilepsy in the rat; and (b) seizure expression in proOFQ/N knockout mice.

Methods: Epilepsy models: kainate and kindling. Northern blot analysis, radioactive in situ hybridization.

Results: Increased proOFQ/N mRNA levels were found in the thalamus (reticular nucleus) after kainate administration. In contrast, ORL‐1 gene expression decreased dramatically in the amygdala, hippocampus, thalamus, and cortex after kainate administration. OFQ/N knockout mice displayed reduced susceptibility to kainate‐induced seizures, in that (a) lethality was reduced, (b) latency to generalized seizure onset was significantly prolonged, and (c) behavioral seizure scores were significantly reduced. Furthermore, kindling progression was delayed in OFQ/N–/– mice.

Conclusions: These data indicate that limbic seizures are associated with increased OFQ/N release in multiple brain areas, causing downregulation of ORL‐1 receptors and activation of OFQ/N biosynthesis in selected areas, and support the notion that the OFQ/N‐ORL‐1 system may play a facilitatory role in ictogenesis and in epileptogenesis.
Effect on Epileptogenesis of Carbamazepine Treatment During the Silent Period of the Pilocarpine Model of Epilepsy
Authors: Capella H. M. , Lemos T.
Published: March 2003

Summary:  Purpose: This study addresses the question of epileptogenesis by investigating the effects of carbamazepine (CBZ) on the silent period of the pilocarpine model of epilepsy.

Methods: Adult Wistar rats were subjected to status epilepticus (SE) induced by pilocarpine and treated with CBZ or saline, i.p, during 56 days. Latency for the first spontaneous seizure, incidence, frequency, and duration of seizures were monitored for ≤56 days after treatment. Hippocampal histologic analysis was performed.

Results: CBZ reduced the frequency and duration of the seizures and the hippocampal damage.

Conclusions: CBZ did not abort the epileptogenesis but minimized the expression of seizures and hippocampal damage.
Functional and Morphological Changes in the Hippocampal Neuronal Circuits Associated with Epileptic Seizures
Authors: Maru Eiichi , Kanda Masutaro , Ashida Hiroshi
Published: March 2003

Summary:  Purpose: We review what is currently known about functional and morphologic plasticity of hippocampal neuronal circuits in animal epilepsy models.

Results: Perforant‐path kindling has been shown to enhance excitatory synaptic transmission in the dentate gyrus significantly, and this enhancement has lasted for ≥1 month after kindling. However, in our rapid kindling experiment with an interstimulus interval of 5 min, perforant‐path kindling resulted in behavioral convulsions and prolonged the afterdischarge duration, but dentate synaptic transmission remained depressed during kindling.

Conclusions: These results indicate that kindling‐induced synaptic potentiation is not necessary for kindling development. Conversely, epileptic seizures have led to the anomalous sprouting of mossy fibers, a process thought to induce hyperexcitation of granule cells. We conclude that the sprouting of mossy fibers did not play a critical role in kindling, because we observed no significant correlation between the mossy fiber sprouting and kindling development. Epileptic seizures also have been shown to increase γ‐aminobutyric acid (GABA)A receptor–mediated inhibition during interictal periods. Although this strengthening of GABAergic inhibition is likely to be a defensive measure against seizure initiation, some studies have suggested that another type of GABAergic response facilitates seizure activity. The possibility of GABAA receptor–mediated excitation during ictal periods is theoretically examined.
Problems and Pitfalls in Developing Countries
Authors: Sylaja Padmavathy N. , Radhakrishnan Kurupath
Published: March 2003

Summary: Despite major challenges, in the last decade several epilepsy centers in the developing world have successfully implemented epilepsy surgery programs and produced results comparable to those from developed countries. If the program is to have a lasting impact, it would be essential to work with and educate the local professionals and public about the recent advances in the treatment of epilepsies. The epilepsy surgery centers in developing countries should initially restrict their surgical candidates to patients with mesial temporal lobe epilepsy and those with circumscribed potentially epileptogenic lesions in whom the epileptogenic zone can be unquestionably localized by using locally available relatively inexpensive and noninvasive technologies, and in whom an excellent postoperative outcome can be guaranteed. It is important for such epilepsy center to assess its capabilities and limitations regularly and adopt a stepwise progressive approach to increasing levels of complex presurgical evaluation and surgical treatment strategies.
Epilepsy Control Program in India: A District Model
Authors: Gourie‐Devi M. , Satishchandra P. , Gururaj G.
Published: March 2003

Summary: Based on data originating from neuroepidemiologic studies in India, epilepsy has been identified as a public health problem. The treatment gap varies from 50 to 70% among persons with epilepsy and is compounded further by limited availability of neurologists, often working in urban metropolises, thus restricting the availability of services in a predominantly rural agrarian country. Cost‐effective, sustainable epilepsy care programs are urgently required in India. To bridge this wide gap, a district model was developed with the central focus on training the district medical officers in providing epilepsy care with sensitization of state health administrators and nodal neurologists to support and sustain the program. Workshops were conducted for all three groups during the period 1999–2001, with the involvement of 21 state health administrators, 148 district medical officers, and 28 neurologists. Preliminary evaluation indicates a growing interest, enthusiastic commitment, and willingness among health professionals to expand epilepsy care to the periphery. The program revealed that it is possible to reach people with epilepsy on the premise of early diagnosis and management, need‐based referral network, and a rational planning for uninterrupted availability of antiepileptic drugs along with education of families. Policy‐level initiatives are required further to transform this on a wider scale and to evaluate the efficacy and effectiveness of this approach.
Assessment of Left and Right Ventricular Systolic and Diastolic Synchronicity in Normal Subjects by Tissue Doppler Echocardiography and the Effects of Age and Heart Rate
Authors: Yu Cheuk‐Man , Lin Hong , Ho Pui‐Ching , Yang Hua
Published: March 2003

Objectives: This study examined inter‐ and intraventricular synchronicity in systole and diastole by tissue Doppler imaging (TDI), and investigated if these parameters and the regional velocities were affected by age and heart rate. Methods: TDI was performed in 106 normal subjects (64.3 ± 9.5 years, 60% male) using three apical views and a six‐basal, six mid‐segmental model. The regional parameters measured off line in both ventricles included peak isovolumic contraction velocity (IVCM), peak sustained systolic velocity (SM), peak early diastolic velocity (EM), peak late diastolic velocity (AM), and the E/AM ratio, as well as their time to these peak velocities: TIVC, TS, TE, and TA. Results: The systole and diastole within the left ventricle (LV) was highly synchronized without difference in TIVC, TS, TE, and TA. However, the right ventricle (RV) was about 20 msec later than the LV for TIVC and TS. For regional velocities, IVCM, SM, EM, and AM were significantly higher in basal than mid‐segments (all
P < 0.001
). In the base of the LV, SM, and EM were the highest at the lateral segment and the lowest at the anterolateral segment. Age and heart rate did not affect systolic velocities or the timing of events. In diastole, age correlated negatively with EM

(r =−0.36 to −0.48, P ≤ 0.001)

and E/AM ratio

(r =−0.37 to −0.51, P ≤ 0.01)

, while increasing heart rate affected AM (

r = 0.17

to 0.43) positively and TE

(r =−0.49 to −0.66, P < 0.001)

and TA

(r =−0.85 to −0.93, P < 0.001)

negatively. Conclusion: (1) Systolic and diastolic functions of the normal hearts are highly synchronized, though LV contraction slightly preceded that of RV. (2) Age and heart rate predominantly affect the diastolic, but not systolic, parameters that need to be taken into account. (ECHOCARDIOGRAPHY, Volume 20, January 2003)
Immunsuppressive Therapie und Knochenstoffwechsel nach Nierentransplantation
Authors: Koller H. , Mayer G.
Published: March 2003

Zusammenfassung: Der Aufschwung der Transplantationsmedizin durch die verbesserte immunsuppressive Therapie hat dazu geführt, dass die Patienten‐ und Transplantatüberlebenszeiten beträchtlich zugenommen haben. Mit diesem Erfolg und der zunehmenden Anzahl an Nierentransplantationen steigt aber auch die Rate an Spätkomplikationen, die unter anderem das Skelettsystem betreffen können. Der Knochenstoffwechsel vor einer Transplantation weist bereits in vielen Fällen (pathologische) Veränderungen auf. Bei Patienten mit chronischer dialysepflichtiger Niereninsuffizienz treten in der Regel zwei typische Knochenveränderungen auf, einerseits eine „Low‐turnover bone disease”, zu der die Osteomalazie und die adyname Knochenkrankheit gehören, oder eine „High‐turnover bone disease” im Rahmen eines sekundären Hyperparathyroidismus. Viele PatientInnen zeigen Manifestationen beider Erkrankungen (gemischte Osteodystrophie). Vor allem in den ersten Monaten nach der Transplantation ist ein starker Knochenmasseverlust zu beobachten. Einer der dafür verantwortlich gemachten Gründe ist die relative starke Immunsuppression in diesen Zeitraum, insbesondere Glukokortikoide scheinen hier eine zentrale Rolle zu spielen. Inwieweit andere Medikamente Einfluss auf den Knochenstoffwechsel haben, ist nicht vollständig geklärt. Derzeit gibt es kaum Studien über eine standardisierte Therapie gegen diesen Knochenabbau, und die Behandlung stützt sich vor allem auf Erfahrungen mit anderen Osteoporoseformen.
Konservative Therapie bei endokriner Orbitopathie: „State of the Art”
Authors: Weissel M.
Published: March 2003

Zusammenfassung: Die vorliegende Übersicht beschreibt die international anerkannten konservativen (vor allem medikamentösen) Maßnahmen bei endokriner Orbitopathie. Diese müssen sich dem Schweregrad der Erkrankung anpassen. Die Objektivierung desselben kann Schwierigkeiten machen, weshalb auf die Bedeutung von entsprechenden Erhebungssystemen, wie zum Beispiel dem Clinical Activity Score, eingegangen wird. Zunächst steht die Sicherstellung einer normalen Schilddrüsenfunktion im Vordergrund. Bei milden Verlaufsformen reichen zusätzliche supportive lokale Maßnahmen. Bei schweren Verlaufsformen ist Kortison in verschiedenen Dosierungen und Applikationsarten das erste Mittel der Wahl. Die Ansprechrate der per os‐Therapie liegt international bei ca. 63 %, jene der intravenösen hochdosierten Bolustherapie bei ca. 77 %. Als Alternative bzw. zur Kombination steht das ebenfalls nebenwirkungsreiche Immunsuppressivum Cyclosporin zur Verfügung. Die Kombination mit Kortison scheint nach übereinstimmenden Berichten der Kortison‐Monotherapie überlegen. Eine weitere Alternative mit hochdosiertem, intravenös verabreichten Immunglobulinen ist zwar nebenwirkungsärmer bei gleicher Erfolgsrate wie die per os‐Kortisontherapie, birgt aber die Infektionsgefahr aller Plasmaderivate in sich und ist außerdem extrem teuer. Abschließend werden noch neuere Therapieversuche mit Immunmodulatoren wie Pentoxifyllin oder Methotrexat, welche bisher nur an wenigen Patienten mit schweren Verlaufsformen – da allerdings mit eindrucksvollem Erfolg – erprobt worden sind, vorgestellt.
Nierenzellkarzinom‐Metastase in einem mikrofollikulären Adenom der Schilddrüse
Authors: Wolf G. , Aigner Reingard Maria , Humer‐Fuchs Ursula , Schwarz Th. , Krippl P. , Wehrschuetz M.
Published: March 2003

Zusammenfassung: Eine 60jährige Patientin, die sich vor zwei Jahren einer Nephrektomie links propter Nierenzellkarzinom unterzogen hatte, kam zur onkologischen F‐18‐Fluorodeoxyglukose‐Positronenemissionstomographie‐Untersuchung. In der Fluorodeoxyglukose‐Positronenemissionstomographie konnte eine signifikant gesteigerte pathologische Fluorodeoxyglukose‐Anreicherung im Bereich des linken Schilddrüsenlappens festgestellt werden. In der Folge wurde ein Schilddrüsenstatus inklusive Tc‐99 m Pertechnetat‐Szintigraphie durchgeführt. Die Szintigraphie zeigte einen heißen Knoten im linken Schilddrüsenlappen. Der histologische Befund des Operationspräparates ergab eine Metastase eines klarzelligen Nierenzellkarzinoms in einem mikrofollikulären Adenom der Schilddrüse. Es handelt sich dabei um eine äußerst seltene Kombination zweier Pathologien.
Effects of potato plants expressing the nptII‐gus fusion marker genes on reproduction, longevity, and host‐finding of the peach‐potato aphid, Myzus persicae
Authors: Alla Salah , Cherqui Anas , Kaiser Laure , Azzouz Hichem , Sangwann‐Norreel Brigitte S. , Giordanengo Philippe
Published: March 2003

Transgenesis developed in the last 20 years offers new possibilities for crop protection. The transgenic process, however, requires the use of marker fusion genes to select and visualize the transformed tissues. Although the expression products of these marker genes are stably expressed in crops, little attention has been given to assess the eventual risks of these recombinant proteins on phytophage populations. Three independent transgenic potato (Solanum tuberosum) clones from the cultivar Désirée (DG5, DG18, and DG20) carrying the commonly used nptII‐gus gene construct and exhibiting different β‐glucuronidase activity (0.843 ± 0.011, 0.576 ± 0.096, and 0.002 ± 0.000 pmol min−1.mg−1, respectively) were evaluated to determine the impact of the encoded proteins on the behaviour, development, reproduction, and demography of the peach‐potato aphid, Myzus persicae, under laboratory‐controlled light and temperature. Our results revealed that the transgenic event can alter aphid physiology or behaviour. Experiments showed a probiotic effect of one transgenic line, the DG5, resulting in reduced prereproductive period and mortality, and enhanced daily fecundity, which was expressed in a greater population growth potential (rm = 0.205 vs. rm = 0.174 of the control). In contrast, aphids fed with the DG18 line exhibited reduced adult survival and reproductive period but no alteration of their demographic parameters (rm = 0.176). Finally, no physiological alteration was induced in aphids fed on a DG20 diet (rm = 0.170). Behavioural experiments conducted in a 4‐choice olfactometer demonstrated that insects were significantly more attracted by the odour of transgenic DG18 potato plant than that of Désirée non‐transformed plant, spending twice as much time in the DG18 plant odour. The two other transformed clones (DG5 and DG20) were as attractive as the non‐transformed cultivar. It is concluded that the β‐glucuronidase expression in potato plants might be responsible for the probiotic effect measured on the feeding aphids, whereas alteration of the foliage odour would result from a pleiotropic effect.
Recognition of a Single Transmembrane Degron by Sequential Quality Control Checkpoints
Authors: Fayadat Laurence , Kopito Ron R.
Published: March 2003

To understand the relationship between conformational maturation and quality control–mediated proteolysis in the secretory pathway, we engineered the well-characterized degron from the α-subunit of the T-cell antigen receptor (TCRα) into the α-helical transmembrane domain of homotrimeric type I integral membrane protein, influenza hemagglutinin (HA). Although the membrane degron does not appear to interfere with acquisition of native secondary structure, as assessed by the formation of native intrachain disulfide bonds, only ∼50% of nascent mutant HA chains (HA++) become membrane-integrated and acquire complex N-linked glycans indicative of transit to a post-ER compartment. The remaining ∼50% of nascent HA++chains fail to integrate into the lipid bilayer and are subject to proteasome-dependent degradation. Site-specific cleavage by extracellular trypsin and reactivity with conformation-specific monoclonal antibodies indicate that membrane-integrated HA++molecules are able to mature to the plasma membrane with a conformation indistinguishable from that of HAwt. These apparently native HA++molecules are, nevertheless, rapidly degraded by a process that is insensitive to proteasome inhibitors but blocked by lysosomotropic amines. These data suggest the existence in the secretory pathway of at least two sequential quality control checkpoints that recognize the same transmembrane degron, thereby ensuring the fidelity of protein deployment to the plasma membrane.
Grb2 Regulates Internalization of EGF Receptors through Clathrin-coated Pits
Authors: Jiang Xuejun , Huang Fangtian , Marusyk Andriy , Sorkin Alexander
Published: March 2003

The molecular mechanisms of clathrin-dependent internalization of epidermal growth factor receptor (EGFR) are not well understood and, in particular, the sequence motifs that mediate EGFR interactions with coated pits have not been mapped. We generated a panel of EGFR mutants and stably expressed these mutants in porcine aortic endothelial (PAE) cells. Interestingly, mutations of tyrosine phosphorylation sites 1068 and 1086 that interact with growth-factor-receptor-binding protein Grb2 completely abolished receptor internalization in PAE cells. Quantitative analysis of colocalization of EGF-rhodamine conjugate and coated pits labeled with yellow-fluorescent-protein–tagged β2 subunit of clathrin adaptor complex AP-2 revealed that EGFR mutants lacking Grb2 binding sites do not efficiently enter coated pits. The depletion of Grb2 from PAE as well as HeLa cells expressing endogenous EGFRs by RNA interference substantially reduced the rate of EGFR internalization through clathrin-dependent pathway, thus providing the direct evidence for the important role of Grb2 in this process. Overexpression of Grb2 mutants, in which the SH3 domains were either deleted or inactivated by point mutations, significantly inhibited EGFR internalization in both PAE and HeLa cells. These findings indicate that Grb2, in addition to its key function in signaling through Ras, has a major regulatory role at the initial steps of EGFR internalization through clathrin-coated pits. Furthermore, the EGFR mutant lacking Grb2 binding sites did not efficiently recruit c-Cbl and was not polyubiquitinated. The data are consistent with the model whereby Grb2 participates in EGFR internalization through the recruitment of Cbl to the receptor, thus allowing proper ubiquitylation of EGFR and/or associated proteins at the plasma membrane.
Analysing a Web‐based e‐commerce learning community: a case study in Brazil
Authors: Joia Luiz Antonio
Published: March 2003

This paper demonstrates usage of a Web‐based participative virtual learning environment, which has enabled graduate students in e‐commerce classes on the Masters in Business Administration Programme taught by the Brazilian School of Public and Business Administration of the Getulio Vargas Foundation, based in Rio de Janeiro, Brazil, to share and disseminate their knowledge among themselves. An illustrative single case study methodology is applied in order to achieve this purpose. The structure of this virtual environment on the Web is analysed. Findings about the participation level of the students in this group, the impact of regional influences – since classes are given throughout Brazil – and the role of the moderator in the leverage of this environment are also presented in this research, which attempts to establish how Internet technology can be effective in the development of virtual learning communities.