bluuebunny/crossref_metadata_2025 huggingface dataset:
Intralamellar relationships within the collagenous architecture of the annulus fibrosus imaged in its fully hydrated state
Authors: Pezowicz Celina A. , Robertson Peter A. , Broom Neil D.
Published: September 2005

The anisotropic, inhomogeneous, multiply collagenous architecture of the annulus reflects the complex pattern of mainly tensile stresses developed in this region of the disc during normal function. Structural and mechanical responses of fully hydrated in‐plane sections taken from within single lamellae of the outer annulus of healthy bovine caudal discs have been investigated using a micromechanical technique in combination with simultaneous high‐resolution differential interference contrast optical imaging. Responses both along and across (i.e. transverse to) the primary direction of the mono‐array of collagen fibres were studied. Stretching along the alignment direction revealed a biomechanical response consistent with the behaviour of an array whose overall strength is governed primarily by the strength of embedding of the fibres in the vertebral endplates, rather than from interfibre cohesion along their length. The mono‐aligned array, even when lacerated, is highly resistant to any further tearing across the alignment direction. Although not visible in the relaxed mono‐arrays, transverse stretching revealed a highly complex set of interconnecting structures embodying hierarchical relationships not previously revealed. It is suggested that these structures might play an important role in the containment under pressure of the nuclear contents. The dramatic differences in rupture behaviour observed along vs. across the primary fibre direction are consistent with the known clinical consequences arising from varying degrees of annular wall damage, and might also explain various types of disc herniation. The lamellar architecture of the healthy disc revealed by this investigation provides an important reference framework for exploring structural changes associated with disc trauma and degeneration.
An immunohistochemical study of the development of sensorimotor components of the early fetal human spinal cord
Authors: Clowry Gavin J. , Moss Jennifer A. , Clough R. Lee
Published: September 2005

Sections from all spinal cord levels from 20 human fetuses, age range 7.5–17 gestational weeks (GW) were immunostained for non‐phosphorylated neurofilaments (to reveal motoneurones, spinocerebellar neurones and other large neurones), the calcium‐binding protein parvalbumin (large proprioreceptive afferents), growth‐associated protein 43 kDa (growing axons), glial fibrillary acidic protein (radial glia), synaptophysin (synaptic terminals) the cell–cell recognition molecule ephrin A4 (EphA4) and the ETS transcription factor Er81 (subclasses of motoneurone and proprioreceptive neurone). Muscle afferents crossed the dorsal horn by 7.5 GW and innervated motoneurones by 9 GW. An alignment of glial fibres guided them from dorsal columns to ventral horn, at right angles to the radial glia. They continued to provide a dense innervation of motoneurone pools up to 17 GW. By 13 GW motoneurones were segregated into distinct columns, all of which expressed EphA4 although only certain lateral groups expressed Er81. However, Er81 expression was more widespread amongst dorsal root ganglion neurones. From 9 GW Clarke's column neurones were identified and by 14 GW were heavily innervated by parvalbumin‐positive afferents whilst their efferent axons could be traced to the lateral funiculus. This investigation contributes towards a timetable for the functional development of human motor control and makes comparisons with well‐studied rodent models.
Ultrastructural anatomy of CALT follicles in the rabbit reveals characteristics of M‐cells, germinal centres and high endothelial venules
Authors: Knop Nadja , Knop Erich
Published: September 2005

Conjunctiva‐associated lymphoid tissue (CALT) is a part of the eye‐associated lymphoid tissue (EALT) at the ocular surface. Its lymphoid follicles are usually characterized by using light microscopy, but its ultrastructure remains largely unknown. In this study, flat whole‐mount conjunctival tissues (n = 42) from 21 young adult rabbits were investigated native in reflected light, and further stained and cleared (n = 6), in paraffin histology sections (n = 6), scanning electron microscopy (SEM,n = 4) and transmission electron microscopy (TEM,n = 4). Secondary lymphoid follicles accumulated into a dense group nasally towards the lacrimal punctum of the lower lid. High endothelial venules (HEV) with typical ultrastructure occurred in the parafollicular zone. The bright germinal centre (GC) contained lymphoblasts, follicular dendritic cells, apoptotic cells and tingible body macrophages. The follicle‐associated epithelium (FAE) was devoid of goblet cells and contained groups of lymphoid cells. TEM showed these cells to be located in cytoplasmic pockets of superficial electron‐lucent cells with a thin cytoplasmic luminal lining that contained a fine filament meshwork and numerous endocytotic vesicles. These M‐cells were sitting between and on top of the ordinary dense epithelial cells that were located basally and formed pillar‐like structures. In stereoscopic SEM, the surface cells were very large, had a polygonal outline and covered cavernous spaces. The rabbit has a CALT with typical follicular morphology, including HEV for regulated lymphocyte migration and epithelial cells with ultrastructural characteristics of M‐cells that allow antigen transport as indicated by the GC‐reaction. The arrangement of these M‐cells on top of and between epithelial pillar cells may reflect a special structural requirement of the multilayered CALT FAE.
Maternal attachment state of mind moderates the impact of postnatal depression on infant attachment
Authors: McMahon Catherine A. , Barnett Byranne , Kowalenko Nicholas M. , Tennant Christopher C.
Published: September 2005

Background:  Empirical studies have revealed a significant, but modest association between maternal depression and insecure mother–child attachment. Across studies, however, a substantial number of mothers with depression are able to provide a sensitive caretaking environment for their children. This paper aimed to explore whether a mother's own state of mind regarding attachment moderated the association between postpartum depression and insecure mother–child attachment.

Methods:  Mothers (n = 111), mainly middle‐class mothers, and their infants participated in a longitudinal study of postnatal depression, maternal attachment state of mind and child attachment. Depression was assessed using a diagnostic interview (at 4 and 12 months) and symptom checklists (at 4, 12 and 15 months). The Adult Attachment Interview was conducted at 12 months and the Strange Situation procedure at 15 months.

Results:  Mothers diagnosed as depressed were more likely to have an insecure state of mind regarding attachment. Infants of chronically depressed mothers were more likely to be insecurely attached; however, the relationship between maternal depression and child attachment was moderated by maternal attachment state of mind.

Conclusions:  Results are discussed with reference to resiliency factors for women with postnatal depression and implications for intervention.
Heritability for adolescent antisocial behavior differs with socioeconomic status: gene–environment interaction
Authors: Tuvblad Catherine , Grann Martin , Lichtenstein Paul
Published: September 2005

Background: Socioeconomic status is often assumed to be of importance for the development of antisocial behavior, yet it explains only a fraction of the variance. One explanation for this paradox could be that socioeconomic status moderates the influence of genetic and environmental effects on antisocial behavior.

Method: TCHAD is a Swedish longitudinal population‐based twin study that contains 1,480 twin pairs born 1985–1986. The present study included 1,133 twin pairs, aged 16–17 years. Antisocial behavior was measured through self‐report. Family socioeconomic status was assessed by parental‐reported education and occupational status. Neighborhood socioeconomic conditions were assessed using five aggregated level variables: ethnic diversity, basic educational level, unemployment level, buying power, and crime‐rate. We used structural equation modeling to test whether socioeconomic status interacted with latent genetic and environmental effects for antisocial behavior.

Results: Genetic influences on antisocial behavior were more important in adolescents in socioeconomically more advantaged environments, whereas the shared environment was higher in adolescents in socioeconomically less advantaged environments. Heritability for antisocial behavior was higher in girls than in boys, irrespective of socioeconomic background.

Conclusions: Our results suggest that different intervention policies should be considered in different socioeconomic areas. In socioeconomically advantaged areas, it might be more fruitful to focus on individually based preventions and treatments. In socioeconomically disadvantaged areas, intervention and prevention policies might be more effective on a community level, to account for shared environmental risk factors.
Pre‐purchase and post‐purchase satisfaction and fashion involvement of female tennis wear consumers
Authors: Chae Myung‐Hee , Black Catherine , Heitmeyer Jeanne
Published: September 2005

This study examined the relationship among pre‐purchase and post‐purchase satisfaction and fashion involvement of women who participated in tennis. As women's activities in sports, including tennis, are growing, it is necessary to investigate their clothing needs in order to meet consumers’ needs. A final sample consisted of 124 women who attended a Cortec United States Tennis Association Women's Pro Tournament. The questionnaires were personally distributed and collected during the tournament. The theoretical base for this study was the Engel, Blackwell, and Miniard model on consumer decision making. There was a positive significant relationship between pre‐purchase satisfaction and post‐purchase satisfaction (P < 0.01). There was a positive significant relationship between pre‐purchase satisfaction and fashion involvement (P < 0.001). Also, there was a positive significant relationship between post‐purchase satisfaction and fashion involvement (P < 0.001). Comfort was identified as the most important clothing attribute and fit the second most important for women to achieve satisfaction before and after purchasing tennis apparel. Seventy‐two percent of the women indicated the need for improved fit of tennis wear. Women of all ages reported garment length as a problem for each garment type. Two major reasons for not purchasing tennis clothing were high prices and inappropriate sizes.
Consumer purchase behaviour for oysters: an empirical study in some state capital cities of Australia
Authors: Liu Yu , Kow Felicia , Grewal Devinder , FitzGerald Des
Published: September 2005

Oysters represent an excellent source of major nutrients, especially proteins, vitamins and minerals. The consumption of oysters in Australia has not grown enough to match to their increased availability. This study is designed to provide information for the oyster industry to better attract more consumers to eat oysters. Six antecedent variables affecting the consumer choice of oysters: quality, safety, labelling, presentation, psychological aspects and preferred values for packaging and price, were identified by principal component factor analysis. A logistic regression approach predicts the consumer choice of oysters using these six factors and the demographic factors in the binary choice model. The outcome of the modelling predicts that the consumer choice of ‘dine in or out’ for oysters is significantly linked to age, gender, residence, labelling and preferred values, while the frequency of eating oysters annually is significantly influenced by the factors of age and preferred values. The oyster promotions such as nutritional marketing of oysters that have low cholesterol, cooking shows and special activities that target specific subsections of the consumer market are recommended in the study.
Altered CD38 expression in thioacetamide‐induced rat model of liver cirrhosis
Authors: Gan Bong Hwa , Ng Geok Lan , Bay Boon Huat , Chang Chan Fong
Published: October 2005

Abstract: Background: Cirrhosis is a gradually developing, chronic disease which involves the whole liver. Here, we have shown that CD38 undergoes altered expression upon thioacetamide‐induced cirrhosis in rats. CD38 is a type II transmembrane glycoprotein that exhibits ADP‐ribosyl cyclase and cADPR hydrolase activities. In this study, the gene and protein expressions of CD38 were investigated in a thioacetamide‐induced rat model of cirrhosis.

Methods: CD38 expression was studied by using real‐time RT‐PCR, immunohistochemistry, and immunoblotting. cADPR content in liver was measured using cycling assay.

Results: There was a significant increase in CD38 mRNA and protein expressions as well as ADP‐ribosyl cyclase activity in cirrhotic liver compared to the control liver. cADPR level was found to be modestly but significantly augmented in cirrhotic liver.

Conclusions: These results raised the possibility that altered CD38 expression and a concomitant elevation of the enzymatic activity as well as cADPR may be involved in the pathogenesis of liver cirrhosis.
Comparison of outcome in patients with cirrhosis and ascites following treatment with albumin or a synthetic colloid:
Authors: Moreau Richard , Valla Dominique‐Charles , Durand‐Zaleski Isabelle , Bronowicki Jean‐Pierre , Durand François , Chaput Jean‐Claude , Dadamessi Innocenti , Silvain Christine , Bonny Corinne , Oberti Frédéric , Gournay Jérôme , Lebrec Didier , Grouin Jean‐Marie , Guémas Eric , Golly Dominique , Padrazzi Bruno , Tellier Zéra
Published: October 2005

Abstract: Background: The question of which colloid (albumin or synthetic colloids) used for plasma expansion following paracentesis or other complications requiring fluid loading in patients with cirrhosis remains controversial.

Aims: To compare outcome and hospital‐related cost in patients with cirrhosis treated with 20% human albumin with those treated with a synthetic colloid (3.5% polygeline).

Methods: The primary end point was occurrence of a first liver‐related complication.

Results: When the trial was prematurely discontinued because of safety concerns about bovine‐derived products, 30 patients were assigned to receive albumin and 38 were assigned to receive a synthetic colloid. Sixty‐three patients were included for ascites removal by paracentesis and five patients for ascites removal by paracentesis and renal impairment. The median time to first liver‐related complication was not significantly longer in the albumin group (20 vs. 7 days). However, the total number of liver‐related complications adjusted to a 100‐day period was significantly lower in the albumin group. The median hospital cost for a 30‐day period was significantly lower in the albumin group (1915 euros vs. 4612 euros).

Conclusions: In patients with cirrhosis and ascites, human albumin appears to be more effective in preventing liver‐related complications than synthetic colloid. This may be associated with decreased hospital costs.
Editorials: Parathyroid Hormone Assay Drift: An Unappreciated Problem in Dialysis Patient Management
Authors: Cantor Tom
Published: September 2005

The Kidney Disease Outcomes Quality Initiative (K/DOQI) bone metabolism guidelines assume that clinicians use the Nichols intact parathyroid hormone immunoradiometric assay (iPTH IRMA) upon which K/DOQI was based. But for more than a decade, virtually all PTH assay results used for routine end‐stage renal disease (ESRD) clinical management have not been generated with this test. Results from the most widely used PTH assays for ESRD patient testing in the United States have varied from 1999 to 2005. The Nichols chemiluminescent Advantage iPTH assay results shifted upwards significantly in 1999 and remained elevated until 2005. From 2003 to 2005, results from the Nichols Advantage Bio‐Intact PTH assay shifted upward on average by 29% to 52%. These changes in the most widely used PTH assays have made use of the K/DOQI guidelines with these assays both inappropriate and potentially harmful to patients.
Recent Advances in Understanding the Malnutrition‐Inflammation‐Cachexia Syndrome in Chronic Kidney Disease Patients: What is Next?
Authors: Kalantar‐Zadeh Kamyar
Published: September 2005

Several recent clinical trials using single modalities to correct the conventional cardiovascular risk factors in patients with chronic kidney disease (CKD) or to improve dialysis dose and techniques in maintenance dialysis patients have failed despite the high rate of cardiovascular mortality in these individuals. Protein‐energy malnutrition and inflammation, two relatively common and concurrent conditions in CKD patients, have been implicated as the main cause of poor short‐term survival in this population. The “malnutrition‐inflammation‐cachexia syndrome” (MICS) appears to be the main cause of worsening atherosclerotic cardiovascular disease in the CKD population. The MICS is associated with low serum cholesterol and homocysteine levels and leads to “cachexia in slow motion.” Hence a reverse epidemiology of cardiovascular risk factors is observed in dialysis patients with a paradoxical association of obesity, hypercholesterolemia, and hyperhomocysteinemia with better survival. Correction of MICS can potentially ameliorate the cardiovascular epidemic in CKD patients. Because MICS is multifactorial, its correction will require an integral approach rather than a single intervention. The ongoing obsession with conventional cardiovascular risk factors largely reflecting overnutrition in a population that suffers from the short‐term consequences of undernutrition and excessive inflammation may well be fruitless. Clinical trials focusing on the causes and consequences of MICS and its modulation using nutritional interventions may be the key to improving survival in these individuals.
Kinetics of β2‐Microglobulin and Phosphate during Hemodialysis: Effects of Treatment Frequency and Duration
Authors: Leypoldt John K.
Published: September 2005

Current understanding of β2‐microglobulin (β2M) and phosphate (or inorganic phosphorus) kinetics during hemodialysis is reviewed. The postdialysis:predialysis concentration ratio for β2M is determined by dialyzer clearance for β2M, treatment time, patient body size (specifically, extracellular fluid volume), and total ultrafiltration volume during the treatment. Evaluation of these treatment parameters can be used to calculate dialyzer clearance for β2M; however, such calculated values are only approximations, since they neglect intradialytic generation, nonrenal (nondialyzer) clearance, and postdialysis rebound of β2M. The detailed kinetics of β2M during hemodialysis are best described using a two‐compartment model. Theoretical predictions from such two‐compartment models suggest that the product of dialyzer clearance for β2M and weekly treatment duration, independent of treatment frequency, is the main determinant of plasma β2M concentrations. The kinetics of phosphate removal during hemodialysis are incompletely understood. Phosphate is removed from both extracellular and intracellular compartments during hemodialysis; the plasma phosphate concentration levels off after the first 1 or 2 hours of treatment and plasma concentrations can rebound even before therapy is complete. Increases in dialyzer clearance of phosphate have been previously achieved only by increasing dialysis membrane surface area or by the use of hemodiafiltration. A four‐compartment model of phosphate kinetics proposed recently by Spalding et al. suggests that the major barrier to phosphate removal is limited transfer of phosphate between the intracellular and extracellular compartments, although other complex factors also play important roles. Theoretical predictions using the model of Spalding et al. suggest that increasing either treatment frequency or treatment duration can increase phosphate removal. The kinetics of β2M are representative of middle molecules whose removal during hemodialysis is governed predominantly by clearance at the dialyzer. In contrast, phosphate removal is limited primarily by its sequestration in the intracellular compartment (and possibly other compartments), not by its clearance at the dialyzer. The kinetics of phosphate may therefore be representative of uremic toxins whose removal is limited by sequestration into compartments or by protein binding. Enhanced removal of both of these uremic toxins using a given therapy will require treatments of increased frequency and longer duration.
ASDIN Original Investigations: Creation of Secondary Arteriovenous Fistulas: Maximizing Fistulas in Prevalent Hemodialysis Patients
Authors: Asif Arif , Unger Stephen W. , Briones Patricia , Merrill Donna , Cherla Gautam , Lenz Oliver , Roth David , Pennell Phillip
Published: September 2005

National Kidney Foundation Dialysis Outcomes Quality Initiative (NKF‐DOQI) guideline 29 suggests that a patient should be evaluated for a secondary arteriovenous fistula (AVF) following each episode of dialysis access failure. Regretfully, it does not appear that this approach is used, even though recent data have emphasized that veins suitable for the creation of a secondary AVF can be identified in dialysis patients who are receiving dialysis via a synthetic arteriovenous graft (AVG) or other type of potentially dysfunctional vascular access. In this study nine patients (five with an AVG and four with an AVF) with vascular access dysfunction undergoing percutaneous interventions were evaluated for secondary AVF creation. All were found to have suitable vascular anatomy and had the AVF created. The secondary fistula was successful in all nine patients with a mean follow‐up of 4.8 ± 1.4 months in post‐AVG cases and 5.6 ± 1.7 months in the post‐AVF patients. In addition, it was possible to continue uninterrupted dialysis without the use of a tunneled dialysis catheter in three of the patients with AVGs. This experience demonstrates the validity and success of this approach to the management of dialysis access dysfunction. In the ongoing effort to optimize vascular health status, we suggest that during percutaneous interventions, patients should routinely have identification of vessels suitable for creation of a secondary AVF.
Fellows’ Forum in Dialysis   edited by Mark A. Perazella: A Patient With an Uncommon Etiology of Intradialytic Hypotension
Authors: Masani Naveed N. , Miyawaki Nobuyuki , Maesaka John K.
Published: September 2005

Hemodialysis is associated with various complications, the most common being intradialytic hypotension (IDH). In the majority of cases, IDH is easily corrected and does not represent a life‐threatening condition. We present a patient in whom IDH was unresponsive to various corrective strategies. A new mitral valve regurgitant lesion was diagnosed that eventually led to the patient's demise. Unusual etiologies of IDH need to be considered, particularly in instances where routine therapeutic measures are ineffective.
Natriuretic Peptides and the Dialysis Patient
Authors: Suresh Mathavakkannan , Farrington Ken
Published: September 2005

The natriuretic peptide family consists of four structurally similar, but genetically distinct molecules with pronounced cardiovascular and renal actions. They are counterregulatory hormones playing an important role in fluid volume homeostasis. Atrial natriuretic peptide (ANP) and B‐type natriuretic peptide (BNP) cause diuresis, natriuresis, and vasodilatation. C‐type natriuretic peptide (CNP) has antimitogenic effects and causes vascular smooth muscle relaxation. Dendroaspis natriuretic peptide (DNP) shares many of the actions of ANP and BNP, but its function in humans is not yet fully understood. Natriuretic peptides have been extensively investigated as biochemical markers of the fluid state. Levels are elevated in disease conditions characterized by fluid overload and are closely related to survival in various cardiac disease states. In the dialysis population, BNP correlates significantly with cardiac function, whereas ANP is sensitive to volume changes during dialysis. However, changes in concentration do not predict achievement of euvolemia, and short half‐life, combined with complicated assay techniques, make ANP a less than satisfactory tool for assessing hydration. BNP is a superior prognosticator for risk stratification in dialysis patients, and serial estimations will help in the identification of occult cardiac disease.
Expression of Multidrug Transporters MRP1, MRP2, and BCRP Shortly after Status Epilepticus, during the Latent Period, and in Chronic Epileptic Rats
Authors: Van Vliet Erwin A. , Redeker Sandra , Aronica Eleonora , Edelbroek Peter M. , Gorter Jan A.
Published: September 2005

Summary:  Purpose: Overexpression of multidrug transporters may play a role in the development of pharmacoresistance by decreasing extracellular drug levels in the brain. However, it is not known whether overexpression is due to an initial insult or evolves more gradually because of recurrent spontaneous seizures. In the present study, we investigated the expression of different multidrug transporters during epileptogenesis in the rat. In addition, we determined whether these transporters affected phenytoin (PHT) distribution in the brain.

Methods: Expression of multidrug resistance–associated proteins MRP1 and MRP2 and breast cancer–resistance protein (BCRP) was examined after electrically induced status epilepticus (SE) by immunocytochemistry and Western blot analysis. Brain/blood PHT levels were determined by high‐performance liquid chromatography (HPLC) analysis in the presence and absence of the MRP inhibitor probenecid.

Results: Shortly after SE, MRP1, MRP2, and BCRP were upregulated in astrocytes within several limbic structures, including hippocampus. In chronic epileptic rats, these proteins were overexpressed in the parahippocampal cortex, specifically in blood vessels and astrocytes surrounding these vessels. Overexpression was related to the occurrence of SE and was present mainly in rats with a high seizure frequency. Brain PHT levels were significantly lower in epileptic rats compared with control rats, but pharmacologic inhibition of MRPs increased the PHT levels.

Conclusions: Overexpression of MRP and BCRP was induced by SE as well as recurrent seizures. Moreover, overexpression was associated with lower PHT levels in the brain, which was reversed through inhibition of MRPs. These data suggest that administration of antiepileptic drugs in combination with specific inhibitors for multidrug transporters may be a promising therapeutic strategy in pharmacoresistant patients.
Gender Differences in Febrile Seizure–induced Proliferation and Survival in the Rat Dentate Gyrus
Authors: Lemmens Evi M. P. , Lubbers Tim , Schijns Olaf E. M. G. , Beuls Emile A. M. , Hoogland Govert
Published: September 2005

Summary:  Purpose: Febrile seizures are fever‐associated early‐life seizures that are thought play a role in the development of epilepsy. Seizure‐induced proliferation of dentate granule cells has been demonstrated in several adult animal models and is thought to be an integral part of epileptogenesis. The aim of the present study was to investigate proliferation and survival of dentate gyrus (DG) cells born after early‐life hyperthermia (HT)‐induced seizures in male and female rats.

Methods: At postnatal day (PN) 10, male and female rats were exposed to heated air to induce seizures. Littermates were used as normothermia controls. Convulsive behavior was observed by two researchers. From PN11 to PN16, rats were injected with bromodeoxyuridine (BrdU) to label dividing cells. The number of BrdU‐immunoreactive cells in the DG was counted at PN17 and PN66.

Results: At PN17, male as well as female HT rats had the same amount of BrdU‐positive cells compared with controls. At PN66, significantly more BrdU‐positive cells were left in HT females (53%) than in controls (44%, percentage of BrdU‐positive cells at PN17), whereas no difference was found between HT males and male controls. The net result of proliferation and survival at PN66 was that female HT rats had the same number of BrdU‐immunoreactive cells as controls, whereas male HT rats had 25% more BrdU‐immunoreactive cells than did controls (p < 0.05).

Conclusions: Early‐life seizures cause a sexually dimorphic cytogenic response that results in an increased population of newborn DG cells in young adult males, while leaving that of young adult females unaltered.
Quinine, a Blocker of Neuronal Cx36 Channels, Suppresses Seizure Activity in Rat Neocortex In Vivo
Authors: Gajda Zita , Szupera Zoltán , Blazsó Gábor , Szente Magdolna
Published: September 2005

Summary:  Purpose: The selective contribution of neuronal gap junction (GJ) communication via connexin 36 (Cx36) channels to epileptogenesis and to the maintenance and propagation of seizures was investigated in both the primary focus and the mirror focus by using pharmacologic approaches with the 4‐aminopyridine in vivo epilepsy model.

Methods: ECoG recording was performed on anesthetized adult rats, in which either quinine, a selective blocker of Cx36, or the broad‐spectrum GJ blockers carbenoxolone and octanol were applied locally, before the induction or at already active epileptic foci.

Results: The blockade of Cx36 channels by quinine before the induction of epileptiform activity slightly reduced the epileptogenesis. When quinine was applied after 25–30 repetitions of seizures, a new discharge pattern appeared with frequencies >15 Hz at the initiation of seizures. In spite of the increased number of seizures, the summated ictal activity decreased, because of the significant reduction in the duration of the seizures. The amplitudes of the seizure discharges of all the patterns decreased, with the exception of those with frequencies of 11–12 Hz. The blockade of Cx36 channels and the global blockade of the GJ channels resulted in qualitatively different modifications in ictogenesis.

Conclusions: The blockade of Cx36 channels at the already active epileptic focus has an anticonvulsive effect and modifies the manifestation of the 1‐ to 18‐Hz seizure discharges. Our findings indicate that the GJ communication via Cx36 channels is differently involved in the synchronization of the activities of the networks generating seizure discharges with different frequencies. Additionally, we conclude that both neuronal and glial GJ communication contribute to the manifestation and propagation of seizures in the adult rat neocortex.
Reversible Cytotoxic Edema in the Splenium of the Corpus Callosum Related to Antiepileptic Treatment: Report of Two Cases and Literature Review
Authors: Prilipko Olga , Delavelle Jacqueline , Lazeyras Francois , Seeck Margitta
Published: September 2005

Summary:  Purpose: Clinically silent lesions localized in the splenium of the corpus callosum (SCC) are a rare finding in the magnetic resonance imaging (MRI) of patients receiving antiepileptic drugs (AEDs). They are usually of benign character but may induce unnecessary complementary examinations if their nature is unrecognized. So far, 22 cases have been described in the literature, for which different etiologies have been proposed. We describe two further cases and discuss the probable lesion etiology.

Methods: We report two cases including a 25‐year‐old male patient and a 12‐year‐old female patient with a transient SCC lesion discovered in the context of a presurgical epilepsy evaluation.

Results: Comprehensive MRIs, including diffusion tensor imaging–based fiber tracking of the lesion, revealed a cytotoxic edema not disrupting neuronal fibers. Serum arginine vasopressin (AVP) measurements revealed an altered secretion during the acute phase in one patient.

Conclusions: On the basis of our results, we hypothesize that the lesion consists of a cytotoxic edema, possibly induced by abrupt AED concentration changes and associated to alterations of AVP secretion.
The Prognostic Value of [18F]FDG‐PET in Nonrefractory Partial Epilepsy
Authors: Weitemeyer Lars , Kellinghaus Christoph , Weckesser Matthias , Matheja Peter , Loddenkemper Tobias , Schuierer Gerhard , Schober Otmar , Ringelstein E. Bernd , Lüdemann Peter
Published: September 2005

Summary:  Purpose: Regional abnormalities of cerebral glucose metabolism, as identified by 18‐fluorodeoxyglucose positron emission tomography (FDG‐PET) have prognostic value regarding the outcome of epilepsy surgery in patients with refractory partial epilepsy. The value of FDG‐PET abnormalities in nonrefractory patients has not been investigated systematically. This study examines whether FDG‐PET could be used for early identification of nonrefractory epilepsy in patients who will become pharmacoresistant later during the course of their disease.

Methods: We investigated interictal abnormalities of cerebral glucose metabolism by using FDG‐PET in 125 consecutive patients with nonrefractory cryptogenic partial epilepsy and normal cranial magnetic resonance imaging (MRI), and we compared relative changes in seizure frequency in 90 patients after ≥2 years of follow‐up.

Results: Regional asymmetry of tracer distribution was seen in 43 of the 90 patients. Forty‐one patients had regional glucose hypometabolism in the temporal and two patients in an extratemporal region. No difference between patients with and without a hypometabolic focus was found regarding seizure freedom after follow‐up. This held true also for the subgroup of patients with epilepsy onset within 1 year before admission. Only patients with regional glucose metabolism showed an increase in seizure frequency. Multivariate analysis showed that only anticonvulsive treatment before index admission and the possibility of localizing the epileptogenic focus by using all available clinical and EEG data were independently associated with continuing seizures after a median follow‐up period of 43 months.

Conclusions: Regional hypometabolism in FDG‐PET is not significantly associated with a lower likelihood of successful anticonvulsant drug therapy in patients with nonrefractory partial epilepsy. Careful analysis of all routinely available clinical and neurophysiologic data has a much better predictive power to identify patients with medically refractory epilepsy early in the course of the disease. However, if PET data are available, they could help in identifying patients with a less benign course.
Subcortical Nuclei Volumetry in Idiopathic Generalized Epilepsy
Authors: Seeck Margitta , Dreifuss Sylvain , Lantz Goran , Jallon Pierre , Foletti Giovanni , Despland Paul‐Andre , Delavelle Jacqueline , Lazeyras Francois
Published: September 2005

Summary:  Purpose: The exact anatomic and neurophysiologic correlates of idiopathic generalized epilepsy (IGE) in humans are still not well understood, although the thalamus has frequently been invoked as the crucial structure in the generation of primary generalized seizures. The few in vivo magnetic resonance (MR)‐based studies in IGE patients suggest an altered cortical/subcortical gray matter ratio, but with no evidence of structural alterations of the thalamus. In this study, we sought to determine the volumes of the other subcortical structures.

Methods: The volumes of the caudate nucleus, putamen, pallidum as well as the thalamus were each determined in both hemispheres in 11 patients with various IGE syndromes, normalized for whole‐brain volumes and then compared with 15 age‐matched controls.

Results: No differences were noted in thalamic volumes, confirming previous reports. However, smaller subcortical volumes were noted in the IGE patients (p < 0.009), mainly due to smaller putamen bilaterally (p ≤ 0.015).

Conclusions: It is speculated that the presence of discrete frontal dysfunction, as noted in neuropsychological studies in IGE patients, indirectly supports our results because the putamen projects predominantly to the frontal cortex. Larger studies with more homogeneous patient populations are needed to determine the robustness of these findings and whether they are specific for particular IGE syndromes.
Effects of Nefiracetam, a Novel Pyrrolidone‐type Nootropic Agent, on the Amygdala‐kindled Seizures in Rats
Authors: Kitano Yutaka , Komiyama Chika , Makino Mitsuhiro , Kasai Yoshio , Takasuna Kiyoshi , Kinoshita Masakazu , Yamazaki Osamu , Takazawa Akira , Yamauchi Toshio , Sakurada Shinobu
Published: September 2005

Summary: Purpose:Nefiracetam (NEF) is a novel pyrrolidonetype nootropic agent, and it has been reported to possess various pharmacologic effects as well as cognition‐enhancing effects. The present study focused on the effects of NEF in amygdala‐kindled seizures and its potential for antiepileptic therapy.

Methods:Effects of NEF on fully amygdala‐kindled seizures and development of amygdala‐kindled seizures were investigated in rats and compared with those of levetiracetam (LEV), a pyrrolidone‐type antiepileptic drug (AED).

Results:In fully amygdala‐kindled rats, NEF (25, 50, and 100 mg/kg, p.o.) decreased afterdischarge induction, afterdischarge duration, seizure stage, and motor seizure duration in a dose‐dependent manner. LEV (25, 50, and 100 mg/kg, p.o.) had no effects on afterdischarge induction and slightly decreased afterdischarge duration, whereas it markedly decreased seizure stage and motor seizure duration. In contrast to the results in fully amygdala‐kindled rats, NEF (25 and 50 mg/kg/day, p.o.) had few or no effects on the development of amygdala‐kindled seizures. As well as fully amygdala‐kindled seizures, LEV (50 mg/kg/day, p.o.) markedly inhibited the development of behavioral seizures without reducing daily afterdischarge duration.

Conclusions:Although NEF possesses potent anticonvulsant effects on fully amygdala‐kindled seizures, it has few or no effects on the development of amygdala‐kindled seizures. LEV shows marked anticonvulsant effects on both phases of kindling. In fully amygdala‐kindled rats, NEF inhibits both electroencephalographic and behavioral seizures, whereas LEV inhibits only behavioral seizures. This double dissociation suggests that NEF has a distinct anticonvulsant spectrum and mechanisms from those of LEV.
Focal Semiologic and Electroencephalographic Features in Patients with Juvenile Myoclonic Epilepsy
Authors: Usui Naotaka , Kotagal Prakash , Matsumoto Riki , Kellinghaus Christoph , Lüders Hans Otto
Published: September 2005

Summary:  Purpose: A few reports have described focal electroencephalographic or clinical features or both of juvenile myoclonic epilepsy (JME), but without video‐EEG documentation. We examined focal clinical and EEG features in patients with JME who underwent video‐EEG monitoring.

Methods: Twenty‐six patients (nine males and 17 females) who had seizures recorded during video‐EEG monitoring were included. Age at seizure onset was 0 to 22 years (mean, 12.3 years), and age at monitoring was 12 to 44 years (mean, 26.5 years). In one patient with left parietooccipital epilepsy, primary generalized tonic–clonic seizures developed after resection of the parietal tumor. Two patients had both temporal lobe epilepsy and JME. Videotaped seizures in each patient were analyzed. Interictal and ictal EEG also were analyzed for any focal features.

Results: Focal semiologic features were observed in 12 (46%) of 26 patients. Six patients had focal myoclonic seizures, and two had Figure 4 sign: one with version to the left, and another had left version followed by Figure 4 sign, and left arm clonic seizure. Their ictal EEGs were generalized at onset but with a lateralized evolution over the right hemisphere. The patient who had both JME and left parietooccipital epilepsy, right arm clonic seizure, and Figure 4 sign was seen during a generalized EEG seizure. Interictally, one patient had temporal sharp waves, and another had run of spikes in the right frontal region.

Conclusions: Fourteen (54%) of 26 patients with JME exhibited focal semiologic or electroencephalographic features or both. Video‐EEG was essential in reaching a correct diagnosis and choosing an appropriate antiepileptic drug regimen.
Hyperhomocysteinemia in Children Treated with Antiepileptic Drugs Is Normalized by Folic Acid Supplementation
Authors: Huemer Martina , Ausserer Bernd , Graninger Gunther , Hubmann Michael , Huemer Christian , Schlachter Kurt , Tscharre Arthur , Ulmer Hanno , Simma Burkhard
Published: September 2005

Summary:  Purpose: To assess the prevalence of hyperhomocysteinemia in pediatric patients treated with antiepileptic drugs (AEDs) and to evaluate the effect of folic acid supplementation on plasma total homocysteine (tHcy) concentrations in hyperhomocysteinemic patients.

Methods: 123 patients from three regional hospitals participated in the study. Patients with hyperhomocysteinemia were included in a 3‐month double‐blind randomized trial testing oral folic acid supplementation (1 mg/day) versus placebo.

Results: Hyperhomocysteinemia (tHcy >10.4 μmol/L) was present in 19 of 123 patients. Patients with hyperhomocysteinemia were older (13.7 ± 4 vs. 11.0 ± 3.9 years) and had significantly lower folate and cobalamin concentrations. Multidrug (two or more) AED treatment and duration of therapy correlated significantly with elevated total homocysteine (tHcy) and low folate. In contrast, polymorphisms in the methylene tetrahydrofolate reductase gene (MTHFR 677 C→T, 1298 A→C, 1793 G→A) had no significant impact on tHcy. Nine of 19 patients with hyperhomocysteinemia were randomized to placebo, whereas the remaining 10 patients received folic acid supplementation. Folic acid supplementation resulted in a significant increase of folate and decrease of tHcy, whereas both parameters remained unchanged in the placebo group.

Conclusions: Hyperhomocysteinemia is present in 15.5% of children receiving long‐term AED treatment. Multidrug treatment and long duration of therapy enhance the risk for hyperhomocysteinemia. Folic acid supplementation significantly reduces tHcy. We recommend assessment of serum folate and plasma tHcy in children receiving AEDs.
A Pilot Study on Brain‐to‐Plasma Partition of 10,11‐Dyhydro‐10‐hydroxy‐5H‐dibenzo(b,f)azepine‐5‐carboxamide and MDR1 Brain Expression in Epilepsy Patients Not Responding to Oxcarbazepine
Authors: Marchi Nicola , Guiso Giovanna , Rizzi Massimo , Pirker Susanne , Novak Klaus , Czech Thomas , Baumgartner Christoph , Janigro Damir , Caccia Silvio , Vezzani Annamaria
Published: September 2005

Summary:  Purpose: We measured the brain‐to‐plasma partition of 10,11‐dihydro‐10‐hydroxy‐5H‐dibenzo(b,f)azepine‐5‐carboxamide (10‐OHCBZ) in epilepsy patients undergoing surgery to alleviate drug‐resistant seizures and administered with different oral doses of oxcarbazepine (OXC). We addressed the possible contribution of the multidrug transporter P‐glycoprotein (P‐gp or MDR1) in determining 10‐OHCBZ brain levels by measuring whether this active metabolite is a substrate of P‐gp and the relation between the level of expression of MDR1 and the drug concentration in the same brain tissue specimens.

Methods: Steady‐state plasma and brain concentrations (Css) of 10‐OHCBZ were determined intraoperatively in 11 patients by high‐performance liquid chromatography (HPLC) with UV detection. The level of expression of MDR1 mRNA was measured in surgically resected brain tissue by reverse transcriptase polymerase chain reaction (RT‐PCR). The ability of 10‐OHCBZ to act as substate of P‐gp was evaluated by measuring its uptake in cell lines expressing different levels of P‐gp, in the presence or absence of a selective P‐gp inhibitor.

Results: OXC was converted to 10‐OHCBZ and to Di‐OHCBZ, the two main metabolites measured in plasma. The brain concentrations of the active metabolite 10‐OHCBZ did not reflect plasma Css. A significant inverse linear correlation was found between 10‐OHCBZ brain‐to‐plasma concentration ratio and the level of brain expression of MDR1 mRNA. In vitro uptake studies demonstrated lower intracellular 10‐OHCBZ levels in cells with higher P‐gp expression. Intracellular drug concentration was increased by XR9576, a specific P‐gp blocker.

Conclusions: Pharmacologic failure of OXC in pharmacoresistant epilepsy is unlikely to be due to alterations in drug metabolism. 10‐OHCBZ does not appear to cross the blood–brain barrier by simple diffusion, and it acts as a substrate of P‐gp. The level of expression of MDR1 is inversely correlated with 10‐OHCBZ concentration in the epileptic tissue. P‐gp may play a role in the pharmacoresistance to OXC by determining the attainment of insufficient concentrations of its active metabolite at neuronal targets.
Prolonged Exposure to Lead Lowers the Threshold of Pentylenetetrazole‐induced Seizures in Rats
Authors: Arrieta Oscar , Palencia Guadalupe , García‐Arenas Guadalupe , Morales‐Espinosa Daniela , Hernández‐Pedro Norma , Sotelo Julio
Published: September 2005

Summary:  Purpose: The aim of this work was to study the effects of prolonged exposure to lead on the threshold of experimental seizures induced by pentylenetetrazole (PTZ).

Methods: The 120 Wistar male rats were allocated randomly into four groups; (A) controls, and lead‐treatment groups (B, C, and D) that received lead acetate in the drinking water for a period of 30 days at concentrations of 250, 500, and 1,000 ppm, respectively. After exposure, a trial of PTZ‐induced seizures was conducted in all groups, and blood contents of lead were determined by atomic absorption spectrophotometry.

Results: Blood lead contents increased in a dose‐dependent manner. Time elapsed to develop the first myoclonic jerk and the tonic–clonic seizure was less in all lead‐exposed groups than in controls. This effect was greater in the groups administered 500 and 1,000 ppm of lead. The required doses of PTZ to induce myoclonic jerks and tonic–clonic seizures were lower in lead‐exposed rats than in controls.

Conclusions: We found a reduction in the threshold for seizures in rats whose blood contents of lead were similar to those of humans from some areas of urban centers with high levels of air pollution.
Association Analysis of Malic Enzyme 2 Gene Polymorphisms with Idiopathic Generalized Epilepsy
Authors: Lenzen Kirsten P. , Heils Armin , Lorenz Susanne , Hempelmann Anne , Sander Thomas
Published: September 2005

Summary:  Purpose: Linkage disequilibrium mapping revealed allelic and haplotypic associations between single‐nucleotide polymorphisms (SNPs) of the gene encoding the malic enzyme 2 (ME2) and adolescent‐onset idiopathic generalized epilepsy (IGE). Homozygote carriers of the associated ME2 haplotype had a sixfold higher risk of IGE compared with any other genotype. The present population‐based association study tested whether genetic variation of the ME2 gene confers susceptibility to common IGE syndromes in the German population.

Methods: The study included 666 German healthy control subjects and 660 German IGE patients (IGE group), of which 416 patients had an age at onset in adolescence (IGEado group). Genotyping was performed for six SNPs and one dinucleotide repeat polymorphism, all located in the ME2 region.

Results: Neither allele nor genotype frequencies of any ME2 polymorphism differed significantly between the controls and the IGE groups (p > 0.22). No hint of an association of the putative risk‐conferring haplotype was seen, when present homozygously, in both IGE groups compared with controls (p > 0.18).

Conclusions: These results do not support previous evidence that genetic variation of the ME2 gene predisposes to common IGE syndromes. Thus if a recessively inherited ME2 mutation is present, then the size of the epileptogenic effect might be too small or not frequent enough to detect it in the present IGE sample.