bluuebunny/crossref_metadata_2025 huggingface dataset:
Hyperhomocysteinemia and other thrombotic risk factors in women with placental vasculopathy
Authors: van der Molen E. F. , Verbruggen B. , Nováková I. , Eskes T. K. A. B. , Monnens L. A. H. , Blom H. J.
Published: August 2005

Objective
To investigate coagulation inhibitors and abnormalities of the homocysteine metabolism, which are related to an increased thrombotic risk, as risk factors for placental vasculopathy.

Design
A case‐control study comparing nonpregnant women with an obstetric history of placental vasculopathy (study group) with nonpregnant women (control group) matched for age and occupation.

Setting
Obstetric outpatient clinic in the University Hospital Nijmegen.

Sample
One hundred and one women in the study group and 92 women in a control group.

Methods
Determinations in blood samples of homocysteine concentrations; the occurrence of 677 C→T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene; protein C activities; activated protein C resistance ratios; concentrations of free protein S antigen; antithrombin III activities; and the occurrence of factor V Leiden mutation.

Results
Increased risk for placental vasculopathy was found in the study group with elevated homocysteine (odds ratio 2.28, 95% CI 1.18–4.39), MTHFR mutation (odds ratio 3.29, 95% CI 1.03–10.5), decreased activated protein C resistance ratio (odds ratio 2.46, 95% CI 1.06–5.72) and protein C (odds ratio 2.01, 95% CI 1.11–3.65). Any combination of two risk factors in the same individual resulted in a 3.40 (95% CI 1.80–6.42) higher relative risk for placental vasculopathy; combinations of three risk factors in a 6.83 (95% CI 1.52–30.7) higher risk.

Conclusions
The thrombotic risk factors decreased levels of activated protein C resistance ratios and protein C, elevated homocysteine and the MTHFR 677 C→T mutation are likely risk factors for placental vasculopathy. Combinations of these risk factors in one individual resulted in synergistic increase of risk.
Maternal thyroid disease: a risk factor for newborn encephalopathy in term infants
Authors: Badawi Nadia , Kurinczuk Jennifer J. , Mackenzie Claire L. , Keogh John M. , Burton Paul R. , Pemberton Patrick J. , Stanley Fiona J.
Published: August 2005

Two previously published studies of term newborn encephalopathy showed that maternal thyroid disease to be a risk factor. From these studies we identified 13 case and three control mothers with thyroid disease and investigated them further. The majority of affected case mothers had idiopathic or autoimmune hypothyroidism. Compared with control mothers, case mothers had fewer thyroid function tests in pregnancy, were more likely to remain on the same dose of medication throughout pregnancy and to have experienced other pregnancy complications. The association between maternal thyroid disease and encephalopathy may be the result of a series of different causal pathways, some of which are suggested by our data.
The Developmental Profile of Seizure Genesis in the Inferior Collicular Cortex of the Rat: Relevance to Human Neonatal Seizures
Authors: McCown Thomas J. , Breese George R.
Published: August 2005

Summary: The ontogeny of seizure genesis within the inferior collicular cortex was characterized in rats ranging in age from 3 days old to adult. Brief electrical stimulation of the right inferior collicular cortex in 30‐day‐old rats evoked poststimulus wild running behavior that coincided with afterdischarge activity in the inferior collicular cortex but not in the adjacent occipital cortex. Similar electrical stimulation in 16‐day‐old rats produced poststimulus wild running and jumping behaviors, which also coincided with afterdischarge in the inferior collicular cortex. In 10‐ and 5‐day‐old rats, electrical stimulation of the inferior collicular cortex produced poststimulus locomotion and coincident afterdischarge activity, but unlike older rats the locomotor behaviors consisted of forelimb paddling, hindlimb treading, and rolling/curling movements of the torso. Identical behaviors can be electrically elicited in 3‐day‐old rats. Although many of the seizure characteristics appear to be similar among the different age groups, 5‐day‐old rats were more sensitive to low frequency stimulation than 16‐day‐old rats, who in turn were more sensitive than adult rats. Thus, the inferior collicular cortex is capable of generating seizure activity in rats as young as 3 days of age, providing a focal model of neonatal seizure genesis.
Effects of Seizures, Kindling, and Carbamazepine on Sleep Organization in Cats
Authors: Gigli Gian Luigi , Gotman Jean
Published: August 2005

Summary: We studied the relationships between epilepsy, sleep, and anticonvulsant drugs in kindled cats. No sleep alteration was present at midkindling. When the animals became fully kindled, a reduction in REM sleep percentage and the number of entries into REM sleep were observed compared to baseline. In addition, with further seizures, an increase in the percentage of wake‐fulness appeared, accompanied by a further reduction in the number of entries into REM sleep. It therefore seems that there is a progressive disruption of sleep, dependent on the increasing number of tonic‐clonic generalized seizures. After a seizure‐free interval, REM sleep and wake‐fulness returned to baseline values. A reduction in the percentage of stage II compared to baseline was found and remained as a long‐term effect of the kindling process. Acute administration of carbamazepine (CBZ) reduced the REM sleep percentage. This effect, paralleled by a reduction in the number of entries into REM sleep, was evident both at baseline and when the animals were fully kindled. After a large number of seizures, however, CBZ administration did not cause a further reduction in the already low percentage of REM sleep. Results are discussed with reference to previous literature. We propose a hypothesis of competition between seizure and REM sleep in the elimination of epileptogenic and hypnogenic factors.
Hippocampal Pyramidal Cell Loss in Human Status Epilepticus
Authors: DeGiorgio Christopher M. , Tomiyasu Uwamie , Gott Peggy S. , Treiman David M.
Published: August 2005

Summary: A pilot case‐control quantitative study of the hippocampus in patients with severe status epilepticus was performed to identify specific patterns of pyramidal cell loss. Pyramidal cell densities from five patients who died following status epilepticus were compared with five normal controls and five controls matched for age, hypoxialischemia, previous epilepsy, and alcohol abuse. Neuronal densities were greatest in the normal control group and least in patients with status epilepticus. Significant reductions were identified in Sommer's sector (prosubiculum and CA1) as well as in CA3 when compared to normal controls.
Prognosis of Epilepsy in Newly Referred Patients: A Multicenter Prospective Study of the Effects of Monotherapy on the Long‐Term Course of Epilepsy
Authors:   Collaborative Group for the Study of Epilepsy
Published: August 2005

Summary:A cohort of 280 previously untreated epilepsy subjects (159 men and 121 women aged 2–81 years) recruited in 14 Italian centers were treated with antiepileptic drug (AED) monotherapy and followed for a median period of 48 months to investigate the rates of seizure remission (i.e., complete control), in general and with reference to various prognostic factors. The cumulative probability of achieving 1‐year remission was 62% by 1 year after onset of treatment, 81% by 2 years, 92% by 3 years, and 98% by 5 years. The corresponding figures for 2‐ and 3‐year remission at 5 years were 92 and 78%, respectively. Sixty‐two patients (22.1%) had no remission period with monotherapy. Remission rates were significantly lower among patients with two or more seizure types and were inversely correlated to the number of seizures before treatment. The rate of seizure relapses during the first year of follow‐up appear to correlate to the risk of developing refractory epilepsy (i.e., with no remission).
Febrile Seizures: Clinical Characteristics and Initial EEG
Authors: Sofijanov N. , Emoto S. , Kuturec M. , Dukovski M. , Duma F. , Ellenberg J. H. , Hirtz D. G. , Nelson K. B.
Published: August 2005

Summary: We examined the relationship between clinical characteristics and EEG classification in all children with febrile seizures examined at the University Pediatric Clinic, Skopje, Yugoslavia between 1982 and 1984. This is the only facility in Macedonia providing EEG or neurologic consultation for children. EEGs were classified as paroxysmally abnormal if they contained spikes, sharp waves, or spike‐wave complexes considered abnormal for age. In all, 22% of the 676 children had an abnormal initial EEG. The most common basis for classification as abnormal was spike‐wave complexes > 3 Hz; the next most common basis was the presence of spikes. Birth weight, gender, accompanying illness, and family history of seizures, and whether the index seizure was single or multiple were not associated with differences in rate of abnormal EEG. Clinically focal index seizures and longer duration were associated with EEG abnormality. Number of previous febrile seizures was associated with an increasing rate of EEG abnormality, from 18% in children with no previous seizures to 63% in those with four or more previous seizures. Age at EEG was linearly related to likelihood of paroxysmal EEG abnormality, both for the total cohort and for the 376 children with no previous seizures. In the total cohort, logistic regression identified leading predictors of abnormal initial EEG to be older age, number of previous febrile seizures, preexisting motor abnormality, and focal seizures. For children with a first febrile seizure, leading predictors were focal seizure, older age, and preexisting motor abnormality.
Neonatal Status Convulsivus, Spongiform Encephalopathy, and Low Activity of Na+/K+ ‐ATPase in the Brain
Authors: Renkawek K. , Renier W. O. , de Pont J. H. H. M. , Vogels O. J. M. , Gabreëls F. J. M.
Published: August 2005

Summary: The first and second child of a family died from neonatal seizures with no detectable brain malformation, metabolic, infectious, or chromosomal etiology. Neuropathological examination of the brain of the second child who died at 11 days revealed a widespread spongy state and a selective vulnerability of the astrocytes characterized by numerous enlarged bare astrocytic nuclei and different forms of astrocyte degeneration. The glial cells were strongly positive for glial fibrillary acidic protein and vimentin immunocytochemical reaction. Cortical measurement of Na+/K+‐ATPase revealed very low enzyme activity. We hypothesize that a defect of Na+/K+ ‐ATPase of the astrocytes could be the common pathogenetic factor for the congenital status convulsivus and for the spongy state.
Kufs’Disease Presenting as Progressive Dementia with Late‐Onset Generalized Seizures: A Clinicopathological and Electrophysiological Study
Authors: Donnet A. , Habib M. , Pellissier J. F. , Régis H. , Farnarier G. , Pelletier J. , Gosset A. , Roger J. , Khalil R.
Published: August 2005

Summary: A 32‐year‐old woman presented with increasing motor difficulties and memory disturbances. Neurological examination only showed mild cerebellar and extrapyramidal symptoms, whereas neuropsychological evaluation disclosed severe cognitive changes consistent with dementia. Her motor and mental status progressively deteriorated until death, which occurred 5 years after the first admission. One year before death, while she was almost bedridden, symptoms of myoclonic epilepsy first appeared, with frequent generalized seizures and generalized myoclonus, occurring especially upon sen sory stimulation or passive joint movements. Pathological examination showed neuronal inclusions typical of Kufs’disease. This case, with primary progressive dementia and late‐onset myoclonic epilepsy, differs from previously reported cases. Three special electrophysiological features were abnormal, “giant”, evoked potentials; unusually marked photosensitivity; and seizure induction by any sensory stimulation.
A Study of Unilateral Brief Focal Atonia in Childhood Partial Epilepsy
Authors: Oguni Hirokazu , Sato Fuminori , Hayashi Kitami , Wang Pen Jung , Fukuyama Yukio
Published: August 2005

Summary: We studied unilateral brief focal atonia (BFA) in seven patients with childhood partial epilepsy. BFA was observed as a transient dropping of one arm lasting from 100 to 150 ms when patients were asked to keep both arms outstretched in front of the body. Close examination using simultaneous video‐polygraphic recordings showed dropping of the arm to correspond exactly with a single sharp and slow wave complex arising from the contralateral centrotemporoparietal region. The BFA occasionally would progress to atonic seizures or atonic absence seizures, when the localized epileptic discharge evolved into generalized discharges. In one patient we found a positive correlation between the intensity of BFA and the amplitude of the contralateral epileptic discharges. A higher amplitude corresponded to more pronounced BFA and a lower amplitude to less pronounced BFA. These results led us to conclude that the apparently interictal single sharp and slow wave complex in the rolandic region may inhibit contralateral motor control, thus producing BFA that corresponds with the spike amplitude.
Effects of a Broad‐spectrum Behavioral Medicine Treatment Program on Children with Refractory Epileptic Seizures: An 8‐Year Follow‐Up
Authors: Dahl JoAnne , Brorson Lars‐Olov , Melin Lennart
Published: August 2005

Summary: We present an 8 year follow‐up on a group of children with refractory epileptic seizures who participated in the early 1980s in a controlled group study on the effects of a broad‐spectrum behavior modification treatment program on children with refractory epileptic seizures. In the original study, 18 children were divided into three groups: behavior modification group, attention control group, and control group. The purpose was to investigate the effects of a learning‐based treatment program superimposed on a regular medical treatment program. Also, the effects of professional attention were evaluated. At the 10 week and 1 year follow‐ups, only the group receiving the behavior modification intervention had a significantly reduced rate of seizure index. The present study investigates these same children 8 years later using the same methods of investigation for an additional 10 week period. The results indicate that a significant reduction in seizures was obtained only for the behavior modification group at the 8 year follow‐up.
Effects of Antiepileptic Drugs on Sperm Motility of Normal Controls and Epileptic Patients with Long‐Term Therapy
Authors: Chen Shun‐Sheng , Shen Meng‐Ru , Chen Tsan‐Ju , Lai Shung‐Long
Published: August 2005

Summary: The in vitro effects of four antiepileptic drugs (AEDs) on human sperm motility were studied with a transmembrane migration method. Sperm motility of epileptic patients receiving chronic AED therapy was also investigated. Sperm motility was measured immediately after semen had been mixed with AED and after a 2‐h preincubation at 37°C. Both in vitro and in vivo studies demonstrated that AEDs inhibited sperm motility. When the drug effect was evaluated after the semen‐AED mixture had been preincubated for 2 h, sperm motility was inhibited to 50% of control at concentrations of 1.59,4.23, and 5.00 mM for phenytoin, carbamazepine, and valproate, respectively. Both with and without preincubation, phenobarbital, even up to 12.92 mM, did not inhibit the motility to <50% of the control. In the in vivo study, poor sperm motility was noted in epileptic patients with long‐term AED therapy despite serum levels within the therapeutic range. Shorter duration of activity of spermatozoa was also observated in these patients. Interference with sperm membrane function by AEDs may be the underlying mechanism.
The Effect of Chronic Phenytoin Treatment on Serum Lipid Profile in Adult Epileptic Patients
Authors: Calandre Elena Pita , Porta Blanca Sinués , de la Calzada Dolores García
Published: August 2005

Summary: Total cholesterol, high‐density lipoprotein (HDL), low‐density lipoprotein (LDL), and very‐low‐density lipoprotein cholesterol, apolipoproteins A, A and B and gamma‐glutamyltransferase (ggt) serum concentrations were measured in 100 adult epileptic patients receiving chronic phenytoin (PHT) treatment and in 100 control subjects. In relation to controls, patients showed higher HDL cholesterol, apolipoproteins A and A, and ggt levels and lower LDL cholesterol and apolipoprotein B values; the significance of the results was greater in women than in men. Among patients, ggt levels were positively correlated with PHT plasma concentrations; likewise, a negative correlation was found between the apolipoprotein A/A, ratio and the PHT and ggt plasma levels, and a positive correlation between the apolipoprotein AIA, ratio and the LDL/HDL cholesterol ratio. These data indicate that PHT exerts a beneficial effect on the serum lipids profile.
Treatment of Intractable Childhood Epilepsy with High‐Dose Valproate
Authors: Ohtsuka Yoko , Amano Rumi , Mizukawa Michiko , Oka Eiji , Ohtahara Shunsuke
Published: August 2005

Summary: Forty‐six children with refractory epilepsy (12 with symptomatic generalized epilepsy, 14 with symptomatic partial epilepsy, and 20 with undetermined epilepsy) were treated by high‐dose (serum level above 100 μg/ml) valproate (VPA) therapy. Monotherapy was used with 34 patients and two drugs with 12. Serum VPA concentrations ranged from 105.1 to 198.4 μg/ml. Assessment of initial response to treatment, after the serum level had reached the appropriate level, showed seizures to be completely controlled in 15 (32.6%) of 46 patients and improved in 12 (26.1%) (50% or more). Follow‐up of more than 6 months after the time of initial response showed control of seizures in 14 (30.4%) and improvement in 11 (23.9%). The initial effect on EEG was the disappearance of epileptic discharges in 3 (6.5%) of 46 patients and marked improvement in 15 (32.6%). Follow‐up revealed the disappearance of epileptic discharges in 7 (15.2%) and marked improvement in 9 patients (19.6%). High‐dose VPA therapy was especially effective for West syndrome and for epilepsy with continuous spike‐waves during slow‐wave sleep. Control of atypical absences and myoclonic seizures was relatively good. Hypofibrinogenemia and thrombocytopenia were sometimes encountered but these side effects were reversible with reduction of dosage.
Abnormal Action‐Potential Bursts and Synchronized, GABA‐Mediated Inhibitory Potentials in an In Vitro Model of Focal Epilepsy
Authors: Troyer Matthew D. , Blanton Mark G. , Kriegstein Arnold R.
Published: August 2005

Summary: Focal, freeze‐induced lesions were made in isolated hemispheres of turtle cerebral cortex in vitro, permitting the investigation of epileptiform discharges in a preparation with preserved intracortical circuitry. Freeze lesions resulted in interictal discharges and occasional ictal‐like events. The interictal discharges were dependent upon activation of non‐NMDA excitatory amino acid receptors and were affected by but did not require NMDA receptor activation. Voltage clamp and current clamp recordings revealed abnormal bursts of low‐amplitude action potentials in 36% of recorded neurons, while large, repetitive inhibitory potentials, mediated by GABAA, receptors, were recorded in 90% of the neurons. Thus, prominent findings in this model include abnormalities of both excitatory and inhibitory activity. Since these changes in neuronal excitability resulted from a localized physical injury, they may resemble the changes that occur in acute posttraumatic epilepsy.
Excitatory Amino Acids Modulate Phosphoinositide Signal Transduction in Human Epileptic Neocortex
Authors: Dubeau F. , Sherwin A. , Olivier A. , Villemure J. , Leblanc R. , Quesney L. F. , Andermann E. , Andermann F.
Published: August 2005

Summary: Stimulation of phosphoinositide (PI) hydrolysis by norepinephrine (NE), carbachol (Carb), and excitatory amino acids (EAAs) was measured in slices prepared from neocortex excised during epilepsy surgery. NE and Carb markedly enhanced PI turnover (EC50: NE, 12 μM; Carb, 661 μM) as reflected by [3H]inositol monophosphate (IP1) accumulation in tissue slices prelabeled with [3H]myoinositol. These effects were dose‐dependent, saturable, and five to six times higher than basal IP1 accumulation. A weaker stimulation (twofold) was observed with quisqualate (QUIS; EC50, 1.1 μM) and glutamate (GLU; EC50, >1 mM), while minimal or no stimulation was seen with kainate (KA) and N‐methyl‐D‐aspartate (NMDA). Agonist‐stimulated PI turnover was significantly reduced in samples from actively spiking epileptic neocortex versus nonspiking areas as defined by electrocorticography (NE, ‐23%, p < 0.05; Carb, ‐44%, p < 0.01). Preincubation of slices with various EEAs inhibited Carb‐induced IP1 formation. The maximal extent of inhibition (1 mM) was both amino acid‐(NMDA > KA > QUIS > GLU) and concentration‐dependent (IC50: NMDA, 5 μM; KA, 3.3 μM; QUIS, 47 μM; GLU, > 1 mM). These data suggest that epileptic activity modulates PI metabolism and alters receptor‐effector coupling. As important mediators of epileptogenesis, EAAs may interfere with the efficiency of this second messenger system.
Localization of the Epileptic Focus During Methohexital‐Induced Anesthesia
Authors: Hufnagel Andreas , Burr Wieland , Elger Christian E. , Nadstawek Joachim , Hefner Gerda
Published: August 2005

Summary: A short anesthesia was provided by methohexital for painless percutaneous removal of subdural electrodes in 27 patients with medically intractable, complex partial seizures who had undergone invasive preoperative evaluation. Electrocorticographic(ECoG) recordings performed before and during the narcosis were submitted to visual (n = 27) and computerized (n = 3) analysis to obtain additional information about the location of the epileptic focus (or foci). The following observations were made: focal epileptiform potentials were induced in 24 of 27 patients (89%); (b) in 20 of these 24, the induced spikes appeared amid or were followed by isoelectric or subdelta activity. These spikes were characterized by high amplitude as well as rhythmic and synchronized appearance over a circumscribed focal area (or areas) known to be spontaneously epileptogenic. This phenomenon, termed spike‐burst‐suppression (SBS) pattern, allowed identification of the primary epileptic focus in many patients with temporal lobe epilepsy. Further‐more, it indicated a good outcome of epilepsy surgery. Computerized analysis of the induced synchronized spikes (n = 3) allowed further delineation of the primary site of epileptogenicity and quantitative comparison of multiple epileptic generators. ECoG recording during deep methohexital‐induced narcosis is a valuable tool for lateralization and delineation of the primary epileptogenic focus.
Temporal Lobectomy in Early Childhood
Authors: Duchowny Michael , Levin Bonnie , Jayakar Prasanna , Resnick Trevor , Alvarez Luis , Morrison Glenn , Dean Patricia
Published: August 2005

Summary: Children with medically resistant temporal lobe seizures that persist into adolescence often experience psychosocial deterioration and medical morbidity. It is therefore especially important to evaluate the contribution of surgical therapy in preadolescent children. We describe our experience with temporal lobectomy in 16 children <12 years (mean age 7 years) who had intractable seizures of temporal lobe origin. Structural lesions were identified on neuroimaging studies in 11 patients. In all patients, the standard anterior temporal lobectomy was tailored according to the extent of the lesion and epileptogenic field. At follow‐up, 11 children were seizure‐free, three were 90% improved, one was 50% improved, and one was unchanged. Neuropathological abnormalities were identified in virtually all children. Prenatally acquired abnormalities of neurogenesis were the most common, whereas mesial temporal sclerosis was found in only two children. We conclude that tailored temporal lobectomy in the first decade of life is highly beneficial in carefully selected children with medically refractory seizures.
Double‐Blind Randomized Study Comparing Brand‐Name and Generic Phenytoin Monotherapy
Authors: Mikati Mohamad , Bassett Nancy , Schachter Steven
Published: August 2005

Summary: Ten patients with well‐controlled seizures receiving chronic phenytoin (PHT) monotherapy for seizure prophylaxis completed a randomized double‐blind crossover study comparing brand‐name and generic PHT. Each patient received the same dose of each preparation for 3 months during which trough PHT concentrations and adverse effects were monitored. The average predose steady‐state total PHT concentration was 11.9 ± 4.9 μg/ ml during brand‐name therapy and 14.2 ± 8.2 pg/ml during generic therapy. The average predose steady‐state free PHT concentrations were 0.93 ± 0.47 μg/ml (brand name) and 1.14 ± 0.64 μg/ml (generic), respectively (p < 0.005). The potency (capsule content) values for the lots used in the study were 99.2% for the brand‐name and 104.6% for generic. Because of the nonlinear MichaelisMenten kinetics of PHT, a 5.4% difference in potency could account for the observed differences in plasma concentrations. When compared with brand‐name PHT therapy, the generic drug was associated with an increase in serum concentration. This increase was consistent with the reported difference in capsule content between the generic and brand‐name lots used in this study.
Important Roles of N‐Methyl‐D‐Aspartate Receptors in Expression of Amygdaloid‐Kindled Seizure Demonstrated by Intraperitoneal Administration of L‐Aspartate in Dimethyl Sulfoxide
Authors: Mori Norio , Wada Juhn A. , Sato Takashi , Saito Hiroki , Kumashiro Hisashi
Published: August 2005

Summary: Intraperitoneally (i.p.) administered L‐aspartate (Asp) (20 mmol/kg) produced no behavioral or EEG change in nonkindled rats. Nonkindled rats that received 18, 19, or 20 mmol/kg Asp, dissolved in 10 or 15% dimethylsulfoxide (DMSO), i.p. developed masticatory movement, head nodding, and myoclonic jerks of the limbs, followed by wild running and subsequent tonic extension of the whole body. In contrast to the effects in nonkindled rats, i.p. injection of Asp 20 mmollkg in 15% DMSO in amygdala‐kindled rats precipitated electroclinical generalized seizures identical to kindled ones. When the kindled amygdala was pretreated with 2‐amino‐7‐phosphonoheptanoic acid (2‐APH), a potent and specific antagonist of N‐methyl‐D‐aspartate (NMDA) receptors, the Asp/DMSO‐induced generalized convulsion identical to kindled amygdala seizure was suppressed. 2‐APH treatment of the contralateral amygdala was without such suppression. The results suggest that (a) Asp is ineffective when given alone (when given with DMSO, however, Asp evokes generalized seizures identical to kindled ones in amygdala‐kindled rats, while it induces a qualitatively different generalized seizure in nonkindled rats; (b) NMDA receptors of the kindled amygdala play an important role in activation of the transsynaptic neurocircuit underlying the expression of kindled amygdala seizure; and (c) DMSO is useful in assessing potential central effects of compounds that do not readily penetrate the blood‐brain barrier (BBB).
Daytime Sleep Tendency Before and After Discontinuation of Antiepileptic Drugs in Preadolescent Children with Epilepsy
Authors: Palm Lars , Anderson Harald , Elmqvist Dan , Blennow Gösta
Published: August 2005

Summary: In 9 preadolescent children treated for epilepsy who had been free from seizures long enough for treatment to be discontinued, daytime vigilance was studied before and after discontinuation of antiepileptic drugs (AEDs). Comparisons were made with healthy controls. Multiple sleep latency test (MSLT), EEG, and a questionnaire were used. As part of the analysis of the MSLT, a new measure, the daily average sleep tendency (DAST), was constructed to overcome the problems with data censoring of the classic MSLT analysis. The patients had significantly (p < 0.001) higher daytime sleep tendency, even after drug discontinuation, than controls, a result that could neither be attributed to AED treatment nor to recent epileptic seizures or complicated epilepsy.
External Leakage from Feeding Gastrostomies in Patients Receiving Valproate Sprinkle
Authors: Jones‐Saete Carolyn , Kriel Robert L. , Cloyd James C.
Published: August 2005

Summary: We reviewed the incidence of external leakage from feeding gastrostomies in 8 patients who received valproate sprinkle (VPA‐S). We also identified a control group of 31 children with feeding gastrostomies who were also cared for in our clinic, but who did not receive VPA‐S. All patients in both groups have had their feeding gastrostomy ≥6 months. Four of 8 children who received VPA‐S through feeding gastrostomies developed problems with recurrent external leakage. The incidence of external leakage in our control group of children who had not received VPA‐S was 2 in 31 (6.4%). We hypothesize that the external leakage is caused by adherence of the undissolved VPA‐S particles to the exterior of the tube, preventing close approximation of the tube to the gastrostomy stoma. In most cases, VPA‐S could continue to be administered and the problem of leakage reduced if the tubes were more frequently changed and/or a larger size were used. Complications with either leakage or occlusion were noted in all patients with the button feeding tube who had received VPA‐S. Because of the especially high complication rate associated with administration of VPA‐S in children with the “button” feeding tubes, we discourage VPA‐S administration to children with that device.
Dihydropyridine Calcium Antagonists in Mice: Blood and Brain Pharmacokinetics and Efficacy Against Pentylenetetrazol Seizures
Authors: Larkin J. G. , Thompson G. G. , Scobie G. , Forrest G. , Drennan J. E. , Brodie M. J.
Published: August 2005

Summary: Dihydropyridine calcium antagonists are candidate anticonvulsants, but little is known of their penetration into brain. Nifedipine (NFD) and nimodipine (NMD) pharmacokinetics were compared in mouse blood and brain, and their activity against pentylenetetrazol (PTZ) was assessed. After intraperitoneal (i.p.) injection, both dihydropyridines achieved peak blood and brain concentrations in 5 min. Estimated blood and brain elimination half‐lives (t1/2) of NMD (16.7 and 22.4 min) were slightly longer than those of NFD (11.2 and 14.7 min). Brain and blood concentrations correlated with both NFD (r = 0.701, p < 0.001) and NMD (r = 0.572, p < 0.001). Injection of the dihydropyridines as a suspension (Tween 80) did not alter brain penetration, although systemic absorption was more erratic. NFD (p < 0.001), NMD (p < 0.021, and carbamazepine (CBZ, p < 0.001) i.p. inhibited PTZ‐induced seizures. Brain concentrations of PTZ were not altered by NFD pretreatment. Combining NFD and CBZ was less effective than giving NFD alone (p < 0.005). NFD (p < 0.002) and NMD (p < 0.001) inhibited PTZ seizures after 2‐week oral dosing, but low dosing was more effective than high dosing (p < 0.002). NFD and NMD cross the blood‐brain barrier (BBB) in mice and inhibit PTZ seizures. A possible therapeutic window was identified, and NFD and CBZ were less effective in combination than singly. A pharmacodynamic interaction may exist, inhibiting effective use of dihydropyridines as adjunctive therapy in epileptic patients.
Moral Development in Adolescence
Authors: Hart Daniel , Carlo Gustavo
Published: August 2005

Themes in the papers in this special issue of the JRA on moral development are identified. We discuss the intersection of moral development research with policy concerns, the distinctive qualities of moral life in adolescence that warrant investigation, the multiple connotations of “moral,” the methods typical of moral development research, and the influences that shape adolescent moral development. Suggestions are made for new methods and new directions in the study of moral development.
Age Changes in Prosocial Responding and Moral Reasoning in Adolescence and Early Adulthood
Authors: Eisenberg Nancy , Cumberland Amanda , Guthrie Ivanna K. , Murphy Bridget C. , Shepard Stephanie A.
Published: August 2005

Age changes' measures of prosocial responding and reasoning were examined. Participants' reports of helping, empathy‐related responding, and prosocial moral reasoning were obtained in adolescence (from age 15–16 years) and into adulthood (to age 25–26 years). Perspective taking and approval/interpersonal oriented/stereotypic prosocial moral reasoning increased from adolescence into adulthood, whereas personal distress declined. Helping declined and then increased (a cubic trend). Prosocial moral judgment composite scores (and self‐reflective empathic reasoning) generally increased from late adolescence into the early 20s (age 17–18 to 21–22) but either leveled off or declined slightly thereafter (i.e., showed linear and cubic trends); rudimentary needs‐oriented reasoning showed the reverse pattern of change. The increase in self‐reflective empathic moral reasoning was for females only. Thus, perspective taking and some aspects of prosocial moral reasoning—capacities with a strong sociocognitive basis—showed the clearest increases with age, whereas simple prosocial proclivities (i.e., helping, sympathy) did not increase with age.
Family and Religious Antecedents of Civic Involvement In Middle Class African American Late Adolescents
Authors: Smetana Judith G. , Metzger Aaron
Published: August 2005

We examined family and religious/spiritual antecedents and correlates of current and intended civic involvement in 76 middle class African American late adolescents (M=18.43 years) who had been followed longitudinally for 3 years. Adolescents' spirituality/religiosity and mothers' current involvement influenced the overall ratings and more specifically, current church and community (but not political) involvement, as assessed on a 14‐item measure expanded from Youniss et al. (1997). In addition, greater family income, earlier spirituality, and less receptivity to mothers in observed dyadic interactions led to more community involvement in late adolescence. Intended civic involvement was predicted by greater spirituality and mothers' (and in exploratory analyses, fathers') observed positive communication (but not mothers' warmth and prosocial behavior) in dyadic interactions 3 years earlier; the effect of middle adolescents' spirituality on late adolescents' ratings of future civic involvement was fully mediated by adolescents' current spirituality/religiosity.
Consumption, Dividends, and the Cross Section of Equity Returns
Authors: BANSAL RAVI , DITTMAR ROBERT F. , LUNDBLAD CHRISTIAN T.
Published: August 2005

We show that aggregate consumption risks embodied in cash flows can account for the puzzling differences in risk premia across book‐to‐market, momentum, and size‐sorted portfolios. The dynamics of aggregate consumption and cash flow growth rates, modeled as a vector autoregression, are used to measure the consumption beta of discounted cash flows. Differences in these cash flow betas account for more than 60% of the cross‐sectional variation in risk premia. The market price for risk in cash flows is highly significant. We argue that cash flow risk is important for interpreting differences in risk compensation across assets.
Board Seat Accumulation by Executives: A Shareholder's Perspective
Authors: PERRY TOD , PEYER URS
Published: August 2005

While reformers have argued that multiple directorships for executives can destroy value, we investigate firms with executives that accept an outside directorship and find negative announcement returns only when the executive's firm has greater agency problems. When fewer agency concerns exist, additional directorships relate to increased firm value. Announcement returns are also higher when executives accept an outside directorship in a financial, high‐growth, or related‐industry firm. Our results suggest that outside directorships for executives can enhance firm value, which has important implications for firms employing executives nominated for outside boards and for policy recommendations restricting the number of directorships.
Confronting the Challenges: Epidemiological Study of Female Sexual Dysfunction and the Menopause
Authors: Dennerstein Lorraine , Hayes Richard D.
Published: August 2005

Introduction

Despite rapid current and anticipated growth in the number of women who will spend a substantial portion of their life span in the postmenopausal period, the nature, incidence, and prevalence of changes in sexual function during and after the menopausal transition remain poorly characterized.

Aim

Challenges inherent in studying the menopausal transition and proposed additions and changes that have emerged from recent consensus conferences on female sexual dysfunction are reviewed.

Methods

Specific topics related to female sexual dysfunction were presented in a Postmenopausal FSD Roundtable in which multidisciplinary international experts participated.

Main Outcome Measure

Expert opinion was based on a review of evidence-based medical literature, presentation, and internal discussion.

Results

Knowledge concerning sexual function in the menopause is limited, in part, due to the difficulty in designing and conducting studies that adequately address these changes over time, and which also permit the effects of menopause to be distinguished from more general changes associated with aging. Moreover, the study of female sexual function and dysfunction is in the midst of significant transition: a tentative definition of the stages of reproductive aging and menopause has recently been advanced, and a set of comprehensive changes to the diagnostic framework that defines female sexual dysfunction is under review.

Conclusions

In spite of fast-moving changes in this field of study, it is possible to reach some tentative conclusions about how women's sexual function changes after menopause: postmenopausal women report a relatively high rate of sexual dysfunction (higher than men). There is a marked decline in sexual interest and frequency of sexual activity. This decline can be ameliorated by a number of psychosocial factors, although vaginal dryness and dyspareunia seem to be driven primarily by declining estradiol. The effects of menopause appear to be incremental and additional to those characteristic of aging.
Biological and Psychosocial Pathophysiology of Female Sexual Dysfunction During the Menopausal Transition
Authors: Graziottin Alessandra , Leiblum Sandra R.
Published: August 2005

Introduction

Although increasing age is a primary determinant of reduced sexual function in older women, hormonal changes may be significant contributors to female (and couples’) sexual dysfunction.

Aim

To analyze the most relevant biological, psychosexual, and/or contextual factors that influence changes in women's sexuality during and after menopause.

Methods

A Postmenopausal FSD Roundtable consisting of multidicsiplinary international experts was convened to review specific issues related to postmenopausal women and sexual dysfunction.

Main Outcome Measure

Expert opinion was based on a review of evidence-based medical literature, presentation, and internal discussion.

Results

Menopause is associated with physiological and psychological changes that influence sexuality: the primary biological change is a decrease in circulating estrogen levels. Estrogen deficiency initially accounts for irregular menstruation and diminished vaginal lubrication. Continual estrogen loss is associated with changes in the vascular, muscular, and urogenital systems, and also alterations in mood, sleep, and cognitive functioning, influencing sexual function both directly and indirectly. The age-dependent decline in testosterone and androgen function, starting in the early 20s, may precipitate or exacerbate aspects of female sexual dysfunction; these effects are most pronounced following bilateral ovariectomy and consequent loss of 50% or more total testosterone. The contribution of progestogens to sexual health and variability in the effects of specific progestogens are being increasingly appreciated. Comorbidities, influenced by loss of sexual hormones, between mood and desire disorders and urogenital and sexual pain disorders are common and remain frequently overlooked in clinical practice. Physical and psychosexual changes may contribute to lower self-esteem, and diminished sexual responsiveness and sexual desire. Nonhormonal factors that affect sexuality are health status and current medication use, changes in or dissatisfaction with partner, partner's health and/or sexual problems, and socioeconomic status.

Conclusion

Determination of the best way to provide optimal management of sexual dysfunction associated with menopause requires additional controlled studies.
HOW WELL DOES THE 9‐POINT HEDONIC SCALE PREDICT PURCHASE FREQUENCY?
Authors: ROSAS‐NEXTICAPA M. , ANGULO O. , O'MAHONY M.
Published: August 2005

One hundred and one consumers assessed three strawberry‐flavored yogurts, using the 9‐point hedonic scale and a purchase intent scale, both blind and with their appropriate cartons. They were then monitored for a year, to determine whether their ratings had any predictive value for their purchase behavior. It was found that the highest rated yogurts tended to be the ones that were purchased during the year. Any correspondence between rank order of rating and of purchase frequency was negligible. Predictions were better when the yogurts were rated with their cartons. The ratings were a better predictor of purchase frequency than price. Various consistency measures were also made.
THOUGHTS ON SUBJECTIVE MEASUREMENT, SENSORY METRICS AND USEFULNESS OF OUTCOMES
Authors: MOSKOWITZ HOWARD R.
Published: August 2005

This note presents a discussion of direct scaling versus paired comparison from the viewpoint of historical, design, field, analytical and interpretation issues. A lot of sensory and consumer research use procedures such as direct measurement, which in turn can lead to major development‐relevant insights. At the same time, other research with the same objectives uses choice methods, which in the author's mind do not, and cannot, lead to these desired development‐relevant insights. It is important to differentiate between the two types of approaches and understand their pros and cons, as well as their intellectual histories. Simply choosing a measurement procedure by the diktat of management or of current fads may actually be counterproductive to the specific task in particular, and to the field of sensory research in general.
A novel osmosensitive voltage gated cation current in rat supraoptic neurones
Authors: Liu Xiao‐Hong , Zhang Wenbo , Fisher Thomas E.
Published: August 2005

The magnocellular neurosecretory cells of the hypothalamus (MNCs) regulate water balance by releasing vasopressin and oxytocin as a function of plasma osmolality. Release is determined largely by the rate and pattern of action potentials generated in the MNC somata. Changes in firing are mediated in part by a stretch‐inactivated non‐selective cation current that causes the cells to depolarize when increased osmolality leads to cell shrinkage. We have obtained evidence for a new current that may regulate MNC firing during changes in external osmolality, using whole‐cell patch clamp of acutely isolated rat MNC somata. In internal and external solutions lacking K+, with high concentrations of TEA, and with Na+ as the only likely permeant cation, the current appears as a slow inward current during depolarizations and yields a large tail current upon return to the holding potential of −80 mV. Approximately 60% of the MNCs tested (79 out of 134 cells) displayed a large increase in tail current density (from 5.2 ± 0.9 to 10.5 ± 1.4 pA pF−1; P < 0.001) following an increase in external osmolality from 295 to 325 mosmol kg−1. The current is activated by depolarization to potentials above −60 mV and does not appear to depend on changes in internal Ca2+. The current is carried by Na+ under these conditions, but is blocked by Cs+ and Ba2+ and by internal K+, which suggests that the current could be a K+ current under physiological conditions. This current could play an important role in regulating the response of MNCs to osmolality.
Epileptiform activity triggers long‐term plasticity of GABAB receptor signalling in the developing rat hippocampus
Authors: Tosetti P. , Ferrand N. , Brun I. Colin‐Le , Gaïarsa J. L.
Published: August 2005

GABAB receptor (GABABR)‐mediated presynaptic inhibition regulates neurotransmitter release from synaptic terminals. In the neonatal hippocampus, GABABR activation reduces GABA release and terminates spontaneous network discharges called giant depolarizing potentials (GDPs). Blocking GABABRs transforms GDPs into longer epileptiform discharges. Thus, GABABR‐mediated presynaptic inhibition of GABA release (GABA auto‐inhibition) controls both spontaneous network activity and excitability in the developing hippocampus. Here we show that extensive release of endogenous GABA during epileptiform activity impairs GABA auto‐inhibition, but not GABABR‐mediated inhibition of glutamate release, leading to hyperexcitability of the neonatal hippocampal network. Paired‐pulse depression of GABA release (PPD) and heterosynaptic depression of glutamate release were used to monitor the efficacy of presynaptic GABABR‐mediated inhibition in slices. PPD, but not heterosynaptic depression, was dramatically reduced after potassium (K+)‐induced ictal‐like discharges (ILDs), suggesting a selective impairment of GABABR‐dependent presynaptic inhibition of GABAergic terminals. Impairing GABA auto‐inhibition induced a 44% increase in GDP width and the appearance of pathological network discharges. Preventing GABA‐induced activation of GABABRs during ILDs avoided PPD loss and most modifications of the network activity. In contrast, a partial block of GABABRs induced network discharges strikingly similar to those observed after K+‐driven ILDs. Finally, neither loss of GABA auto‐inhibition nor network hyperexcitability could be observed following synchronous release of endogenous GABA in physiological conditions (during GDPs at 1 Hz). Thus, epileptiform activity was instrumental to impair GABABR‐dependent presynaptic inhibition of GABAergic terminals. In conclusion, our results indicate that endogenous GABA released during epileptiform activity can reduce GABA auto‐inhibition and trigger pathological network discharges in the newborn rat hippocampus. Such functional impairment may play a role in acute post‐seizure plasticity.
Nano-Scale Effects in the Sliding and Rolling of a Cylinder on a Substrate
Authors: Sari O¨. T. , Adams G. G. , Mu¨ftu¨ S.
Published: August 2005

The behavior of a nano-scale cylindrical body (e.g., a fiber), lying on a substrate and acted upon by a combination of normal and tangential forces, is the subject of this investigation. As the scale decreases to the nano level, adhesion becomes an important issue in this contact problem. Thus, this investigation treats the two-dimensional plane strain elastic deformation of both the cylinder and the substrate during a rolling/sliding motion, including the effect of adhesion using the Maugis model. For the initiation of sliding, the Mindlin approach is used, whereas for rolling, the Carter approach is utilized. Each case is modified for nano-scale effects by including the effect of adhesion on the contact area and by using the adhesion theory of friction for the friction stress. Analytical results are given for the normal and tangential loading problems, including the initiation of sliding and rolling in terms of dimensionless quantities representing adhesion, cylinder size, and applied forces.