bluuebunny/crossref_metadata_2025_split huggingface dataset:
GABAA receptor‐mediated activation of L‐type calcium channels induces neuronal excitation in surgically resected human hypothalamic hamartomas
Authors: Kim Do Young , Fenoglio Kristina A. , Simeone Timothy A. , Coons Stephen W. , Wu Jie , Chang Yongchang , Kerrigan John F. , Rho Jong M. 
Published: May 2008

Summary
Purpose: The human hypothalamic hamartoma (HH) is a rare, intrinsically epileptogenic lesion associated with gelastic seizures, but the underlying mechanisms remain unclear. Here, we examined the role of GABAA receptors in surgically resected HH tissue.
Methods: HH tissue slices (350 μm) were studied using cellular electrophysiological, calcium imaging, and immunocytochemical techniques.
Results: Two neuronal cell types were seen: small (10–16 μm) spontaneously firing GABAergic neurons and large (20–28 μm) quiescent neurons. In gramicidin‐perforated patch recordings, muscimol (30 μM) induced membrane depolarization in 70% of large (but not small) neurons and a concomitant rise in intracellular calcium. These responses were blocked by bicuculline methiodide (50 μM). Depolarizing neurons also exhibited more positive reversal potentials (Emuscimol) and significantly higher intracellular chloride concentrations compared to those that hyperpolarized. The cation chloride co‐transporters NKCC1 and KCC2 were coexpressed in the majority of large neurons, but fluorometric measurements revealed that 84% of large HH neurons expressed solely or relatively more NKCC1. Bumetanide (20 μM), a NKCC1 antagonist, partially suppressed muscimol‐induced excitation in large neurons. Concordant with robust expression of CaV1.2 and CaV1.3 subunits in HH neurons, the L‐type calcium channel blocker nifedipine (100 μM) prevented muscimol‐induced neuronal excitation.
Conclusions: GABAA receptor‐mediated excitation, due in part to differential expression of NKCC1 and KCC2 and subsequent activation of L‐type calcium channels, may contribute to seizure genesis in HH tissue. Given the ready availability of L‐type calcium channel blockers, our results have clinical ramifications for the treatment of seizures associated with HH lesions.
Do observer and self‐reports of ictal eye closure predict psychogenic nonepileptic seizures?
Authors: Syed Tanvir U. , Arozullah Ahsan M. , Suciu Gabriel P. , Toub Julia , Kim Hyunmi , Dougherty Michelle L. , Wehner Tim , Stojic Andrey , Syed Ishtiaq , Alexopoulos Andreas V. 
Published: May 2008

Summary
Purpose: Diagnostic delay in distinguishing psychogenic nonepileptic seizures (PNES) from epileptic seizures may result in unnecessary therapeutic interventions and higher health care costs. Previous studies demonstrated that video‐recorded eye closure is associated with PNES. The present study prospectively assessed whether observer or self‐report of eye closure could predict PNES, prior to video‐EEG monitoring.
Methods: Adults referred to an epilepsy monitoring unit (EMU) were prospectively enrolled into the study. At baseline, self‐report of eye closure was assessed by questionnaire, and observer report was obtained by interview. Physicians viewed video clips independent of EEG tracings and determined the duration of eye closure during PNES and epileptic seizures. We evaluated whether video‐recorded eye closure identified an episode as PNES using random effects models that accounted for episode clustering by subject. The utility of observer and self‐report of eye closure in predicting a diagnosis of PNES was tested using logistic regression.
Results: Of 132 enrolled subjects, 112 met study criteria during EMU stay for either PNES (n = 43, 38.4%) or epilepsy (n = 84, 75.0%). Fifteen of the 43 PNES subjects (34.9%) had coexisting epilepsy. Self and observer reports of eye closure were neither sensitive nor specific for the diagnosis of PNES. Self‐report of eye closure more accurately predicted actual video‐recorded eye closure than observer report. Video‐recorded eye closure was 92% specific, but only 64% sensitive for PNES identification.
Discussion: Neither observer nor self‐report of eye closure, prior to VEEG monitoring, predicts PNES. Video‐recorded eye closure may not be as sensitive an indicator of PNES as previously reported.
Are MRI‐detected brain abnormalities associated with febrile seizure type?
Authors: Hesdorffer Dale C. , Chan Stephen , Tian Hong , Allen Hauser W. , Dayan Peter , Leary Linda D. , Hinton Veronica J. 
Published: May 2008

Summary
Objective: Whether magnetic resonance imaging (MRI) is informative in febrile seizures (FS) is unknown. We undertook a study to determine the frequency of MRI‐detected brain abnormalities and to evaluate their association with FS type and with specific features of complex FS.
Methods: A prospective cohort study, from 1999 to 2004, included children with first FS from one Pediatric Emergency Department. MRI of the brain was performed within 1 week of the seizure. FS type was categorized by experts blind to the prior clinical history and MRI results. MRI examinations were read blind to the child's clinical history and FS type, and interviewers were blind to MRI results.
Results: In 159 children with a first FS, imaging abnormalities occurred in 12.6% (N = 20). Eight of the 54 with complex FS had imaging abnormalities compared to 12 of the 105 with simple FS (n.s.). Compared to children with simple FS, children with both focal and prolonged FS (N = 14) were more likely to have imaging abnormality (OR = 4.3, 95% CI = 1.2–15.0), even after adjustment for abnormal neurological examination. Imaging abnormalities included those known to be associated with seizures (e.g., focal cortical dysplasia) and those not typically associated with seizures (e.g., subcortical focal hyperintensities ≥ 5 mm).
Discussion: Our data suggest that brain abnormalities may lower seizure threshold in febrile children, predisposing to the development of FS. Clinical management was unaffected and therefore these data do not alter the recommendation that MRI is unnecessary in children with FS, without some other neurological indication.
Cytogenesis in the dentate gyrus after neonatal hyperthermia‐induced seizures: What becomes of surviving cells?
Authors: Lemmens Evi M.P. , Schijns Olaf E.M.G. , Beuls Emile A.M. , Hoogland Govert 
Published: May 2008

SummaryPurpose:Febrile seizures (FS) are early‐life seizures thought to play a role in epileptogenesis. By labeling cells that were dividing immediately following experimental FS, we previously demonstrated that significantly more of these newborn cells in the dentate gyrus (DG) survived 8 weeks later, relative to animals that did not experience FS. The purpose of the present study was to determine the long‐term fate of these newborn cells.Methods:On postnatal day (PN) 10, hyperthermia‐induced seizures (HT, ±42°C core temperature) were evoked in Sprague‐Dawley rats and littermates were used as normothermia controls (NT, ±35°C core temperature). From PN11 to PN16, rats were injected with bromodeoxyuridine (BrdU) to label dividing cells. At PN66, we evaluated the number of BrdU‐labeled cells in the DG that colocalized with the neuronal marker NeuN, glial marker glial fibrillary acidic protein (GFAP), neuronal excitatory amino acid transporter 3 (EAAT3), GABAergic neuronal marker glutamic acid decarboxylase 67 (GAD67) or microglia marker tomato lectin (TL).Results:In all rats, almost all BrdU‐labeled cells in the DG, that showed double‐labeling, colocalized with NeuN, and rarely with GFAP, GAD67, or TL. In NT controls and HT rats that did not experience seizures (“HT‐no seizures”), ∼23% of BrdU‐labeled cells colocalized with EAAT3, which was significantly different from 14% in HT rats that did experience seizures (HT + FS).Discussion:Early‐life seizures decrease the population of newborn cells that survive and mature into EAAT3‐positive neurons and do not affect the GABAergic cell population. This may affect hippocampal physiology in young adulthood.
Effects of early‐life LiCl‐Pilocarpine‐induced status epilepticus on memory and anxiety in adult rats are associated with mossy fiber sprouting and elevated CSF S100B protein
Authors: De Oliveira Diogo Losch , Fischer Alice , Jorge Renan Sanna , Da Silva Mariane Castro , Leite Marina , Gonçalves Carlos Alberto , Quillfeldt Jorge Alberto , Souza Diogo Onofre , E Souza Tadeu Mello , Wofchuk Susana 
Published: May 2008

Summary
Purpose: This study investigated putative correlations among behavioral changes and: (1) neuronal loss, (2) hippocampal mossy fiber sprouting, and (3) reactive astrogliosis in adult rats submitted to early‐life LiCl‐pilocarpine‐induced status epilepticus (SE).
Methods: Rats (P15) received LiCl (3 mEq/kg, i.p.) 12–18 h prior pilocarpine (60 mg/kg; s.c.). At adulthood, animals were submitted to behavioral tasks and after the completion of tasks biochemical and histological analysis were performed.
Results: In SE group, it was observed an increased number of degenerating neurons in the CA1 subfield and in the hilus of animals 24 h after SE. At adulthood, SE group presented an aversive memory deficit in an inhibitory avoidance task and the animals that presented lower latency to the step down showed a higher score for mossy fiber sprouting. In the light‐dark exploration task, SE rats returned less and spent less time in the light compartment and present an increased number of risk assessment behavior (RA). There was a negative correlation between the time spent in the light compartment and the score for mossy fiber sprouting and a positive correlation between score for mossy fiber sprouting and number of RA. LiCl‐pilocarpine‐treated animals showed higher levels of S100B immunocontent in the CSF as well as a positive correlation between the score for sprouting and the GFAP immunocontent in the CA1 subfield, suggesting an astrocytic response to neuronal injury.
Conclusions: We showed that LiCl‐pilocarpine‐induced SE during development produced long‐lasting behavioral abnormalities, which might be associated with mossy fiber sprouting and elevated CSF S100B levels at adulthood.
Evaluation of epileptogenic networks in children with tuberous sclerosis complex using EEG‐fMRI
Authors: Jacobs Julia , Rohr Axel , Moeller Friederike , Boor Rainer , Kobayashi Eliane , LeVan Meng Pierre , Stephani Ulrich , Gotman Jean , Siniatchkin Michael 
Published: May 2008

Summary
Purpose: Ninety percent of patients with tuberous sclerosis complex (TSC) have epilepsy. Identification of epileptogenic areas can be difficult and studies are needed to characterize the epileptogenic network in more detail.
Methods: Five children with TSC and focal epilepsy were studied using simultaneous EEG and functional MRI recordings. Tubers were marked by a neuroradiologist on the anatomical MRI. Spike‐associated BOLD (blood oxygenation level‐dependent) responses were superimposed with lesions.
Results: Thirteen different types of interictal epileptiform discharges (IED) were analyzed with 12 showing a BOLD response, all involving more than one tuber. Five studies had tubers with activations exclusively within the lesion, three studies had lesional activations extending to perilesional areas, and two studies had activations involving exclusively perilesional areas of at least one tuber. Deactivations exclusively within a tuber were found in six studies, lesional deactivations extending to perilesional areas were found in four studies, and tubers with exclusively perilesional deactivations were found in five studies. A BOLD response was found in at least one tuber in the lobe of IED generation and presumed seizure onset (according to telemetry) in all patients. In four patients, the same tubers were involved following different IED localizations. The observed changes were always multifocal, sometimes involving tubers distant from the IED field.
Discussion: These findings suggest extended epileptogenic networks in patients with TSC, which exceed networks described in PET and SPECT studies. It was possible to identify specific interictally active tubers. EEG‐fMRI provides a noninvasive method to select tubers and areas at their borders for further presurgical investigations.
Quality of Pharmacotherapy and Outcomes for Older Veterans Discharged from the Emergency Department
Authors: Hastings S. Nicole , Schmader Kenneth E. , Sloane Richard J. , Weinberger Morris , Pieper Carl F. , Goldberg Kenneth C. , Oddone Eugene Z. 
Published: May 2008

OBJECTIVES: To determine whether suboptimal pharmacotherapy increases the risk of adverse outcomes in older adults discharged from the emergency department (ED).DESIGN: Retrospective, cohort study.SETTING: Academically affiliated Veterans Affairs Medical Center.PARTICIPANTS: Nine hundred forty‐two veterans aged 65 and older discharged from the ED.MEASUREMENTS: The primary independent variable, suboptimal pharmacotherapy, was based on drugs‐to‐avoid criteria, drug–drug interactions, drug–disease interactions, or failure to satisfy explicit quality indicators (QIs). An adverse outcome was defined as one or more repeat ED visits or hospitalizations or death within 90 days of ED discharge.RESULTS: Four hundred twenty‐one patients were prescribed a new medication at ED discharge. Of these, 134 (31.8%) had suboptimal pharmacotherapy; 49 (11.6%) were prescribed a drug to avoid, 53 (12.6%) received a drug that introduced a new drug–drug interaction, 24 (5.7%) were given a drug that introduced a drug–disease interaction, and 74 (17.6%) did not have a QI satisfied. Overall, 320 patients (34.0%) experienced an adverse outcome within 90 days. Multivariable analyses suggested a trend toward greater risk of adverse outcomes in patients with suboptimal pharmacotherapy (hazard ratio=1.32, 95% confidence interval=0.95, 1.84).CONCLUSION: A substantial number of older male veterans discharged from the ED may be at risk for adverse events due to suboptimal prescribing and inadequate medication monitoring. Efforts to improve the quality of pharmacotherapy in this vulnerable population are warranted.
Use of Urinary Collection Devices in Skilled Nursing Facilities in Five States
Authors: Rogers Mary A. M. , Mody Lona , Kaufman Samuel R. , Fries Brant E. , McMahon Laurence F. , Saint Sanjay 
Published: May 2008

OBJECTIVES: To assess use of urinary collection devices (external, intermittent, and indwelling catheters; pads or briefs) and examine predictors of indwelling catheters in skilled nursing facilities (SNFs).DESIGN: Retrospective cohort study.SETTING: SNFs in California, Florida, Michigan, New York, and Texas.PARTICIPANTS: All patients admitted to SNFs in 2003 who remained there for 1 year (N=57,302).MEASUREMENTS: Characteristics of patients who used different collection strategies (indwelling, intermittent, and external catheterization; pads or briefs) and predictors of indwelling urinary catheterization from the Nursing Home Minimum Data Set using multinomial logistic regression.RESULTS: The prevalence of indwelling catheterization was 12.6% at admission and 4.5% at the annual assessment (P<.001). Intermittent and external catheterization were infrequently used (<1% at admission and annual assessment). Paraplegia, quadriplegia, multiple sclerosis, and comatose state were strongly associated with indwelling catheterization. Male residents were more likely to use an indwelling catheter at every assessment, as were obese patients; individuals with diabetes mellitus, renal failure, skin conditions, deep vein thrombosis, aphasia, or end‐stage disease; and those who were taking more medications.CONCLUSION: Coinciding with federal regulations, urinary catheterization was lower than has been reported previously and declined over time. Further reduction should be targeted at the evaluation of skin problems, appropriateness of multiple medications, and alternative measures in patients with diabetes mellitus, obesity, deep vein thrombosis, and communication problems.
Effect of viral nucleic acid testing on contamination frequency of manufacturing plasma pools
Authors: Nübling C. Micha , Unkelbach Uwe , Chudy Michael , Seitz Rainer 
Published: May 2008

BACKGROUND:In Europe, all plasma pools used for manufacturing of plasma derivatives must be tested negative for hepatitis C virus (HCV) RNA by nucleic acid amplification techniques (NAT) with a defined minimal sensitivity. For a subset of pools, quantitative B19V DNA NAT is also mandatory. NAT for further viral targets was introduced by most of the manufacturers on a voluntary basis. The contamination frequency of plasma pools with HCV RNA, human immunodeficiency virus (HIV)‐1 RNA, and hepatitis B virus (HBV) DNA was investigated with representative pools before and after introduction of NAT.STUDY DESIGN AND METHODS:A total of 873 pools from 1996 and 331 pools from 2006 were analyzed for the detection of HCV RNA, HIV RNA, and HBV DNA with an automated multiplex NAT system. The pools were obtained from different manufacturers and the source material was of European and US origin.RESULTS:HCV RNA, HIV‐1 RNA, and HBV DNA were detectable in plasma pools from 1996 with the following frequencies: 17.8 percent (HCV RNA), 0.8 percent (HIV‐1 RNA), and 0.5 percent (HBV DNA). Viral genome concentrations were up to 3 × 104 IU HCV RNA per mL and 7 × 103 IU HIV RNA per mL, whereas HBV DNA was below the quantitation limit of the quantitative NAT assay. Among the pools from 2006, one pool (0.3%) was found HCV RNA–positive at low titer (<10 IU/mL), whereas no HIV RNA or HBV DNA was detectable in any pool.CONCLUSION:The results imply that the introduction of NAT systems for the detection of viral genomes has largely reduced the contamination frequency and viral loads of manufacturing plasma pools and thereby improved the safety margin for human medicinal products manufactured from human plasma. Even with NAT, however, low‐titer contamination may occur, which will be coped with by virus inactivation steps included into the manufacturing of plasma derivatives.
Long‐term survival rate of pediatric patients after blood transfusion
Authors: Gauvin France , Champagne Martin A. , Robillard Pierre , Le Cruguel Jean‐Pierre , Lapointe Hélène , Hume Heather 
Published: May 2008

BACKGROUND: Studies in adults report posttransfusion survival rate (PTSR) at 1 to 10 years of 41 to 67 percent. There are no published studies specifically addressing PTSR in pediatric patients. The objectives of this study were to evaluate PTSR and risk factors associated with death in children receiving transfusions.STUDY DESIGN AND METHODS: A database of all patients receiving their first transfusion between 1990 and 1992 at Sainte‐Justine Hospital (SJH) was used. Patients' demographic data, primary diagnosis, surgical procedures, and information on all labile components transfused were collected. Death was confirmed by the SJH database, RAMQ (universal health care provider for Québec residents), and the Quebec Commission for Access to Information (death certificate).RESULTS: The study population consisted of 1100 children. Median age was 16 months (range, 0‐204 months). The most frequent primary diagnoses were cardiac disease (22%), prematurity (21.5%), malignant disease (11%), and hematologic disease (9.5%). Patients received a median of three transfusions (range, 1‐126). PTSR was 86.9 percent at 1 year and 82.3 percent at 10 years. For nonsurvivors, median survival time was 22 days. Multivariate analysis showed that significant risk factors for death are age of less than 1 month, a diagnosis of malignant disease, more than 20 transfusions, and administration of more than one type of blood component.CONCLUSION: PTSR in children receiving their first transfusion between 1990 and 1992 was considerably higher than the PTSR reported in adults. Death occurred early after the first transfusion; survival rate remained relatively stable thereafter.
Quantitative expression of Toll‐like receptor‐2, ‐4, and ‐9 in dendritic cells generated from blasts of patients with acute myeloid leukemia
Authors: Schmitt Anita , Li Li , Giannopoulos Krzysztof , Greiner Jochen , Reinhardt Peter , Wiesneth Markus , Schmitt Michael 
Published: May 2008

BACKGROUND: Dendritic cells (DCs) generated from leukemic blasts constitute a promising tool in immunotherapy for acute myeloid leukemia patients (AML‐DCs), because AML‐DCs express human leukocyte antigens and costimulatory molecules such as CD40, CD80, and CD86 at a higher level than leukemic blasts. Potentiation of AML‐DC vaccine might become feasible by the addition of adjuvants such as lipopolysaccharides (LPS) or CPG‐rich oligodeoxyribonucleotides binding to Toll‐like receptors (TLR) and inducing a stronger Type 1 T‐cell response.STUDY DESIGN AND METHODS: mRNA and protein expression of TLR‐2, ‐4, and ‐9 were analyzed with quantitative real‐time polymerase chain reaction, Western blot, and flow cytometry for mature monocyte‐derived DCs generated from 14 AML patients versus 14 healthy volunteers (HV‐DCs), and the response of the AML‐ and HV‐DCs to different microbial TLR ligands was determined by enzyme‐linked immunosorbent assay for the proinflammatory cytokines tumor necrosis factor (TNF)‐α, inducible protein (Ip)‐10, and interleukin (IL)‐6.RESULTS: AML‐DCs and HV‐DCs strongly expressed TLR‐2 and TLR‐4, while TLR‐9 was expressed at a lower level in both groups. There was no significant difference in TLR expression between the two groups of AML‐DCs and HV‐DCs. In accordance with the TLR expression levels, DCs generated from both AML patients and HVs responded to the known microbial ligands peptidoglycan (PGN) and lipoteichoic acid for TLR‐2 and LPS as ligand for TLR‐4, by producing TNF‐α and IL‐6. A response to the ODNs 2006 and 2216 binding to TLR‐9 was only detected in AML‐DCs.CONCLUSION: Microbial ligands like ODNs and LPS constitute promising adjuvants for enhancing (AML‐) DC vaccines.
Cesarean section due to fetal distress increases the number of stem cells in umbilical cord blood
Authors: Manegold Gwendolin , Meyer‐Monard Sandrine , Tichelli Andre , Pauli Doris , Holzgreve Wolfgang , Troeger Carolyn 
Published: May 2008

BACKGROUND: Umbilical cord blood (UCB) can be used as hematopoietic stem cell source for transplantation. The success of a transplantation is highly correlated with the number of total nucleated cells (TNCs) and CD34+ cells in the UCB. Certain obstetric factors increase the yield of stem cells in the UCB. It is necessary to evaluate optimal conditions in labor to decrease the rate of sample rejection due to low cell count. No data exist regarding the difference between primary and secondary Cesarean sections in terms of efficacy of stem cell harvesting.STUDY DESIGN AND METHODS: Seventy‐nine consecutive UCB units from women who had a Cesarean section between 1997 and 2003 were included. The number of TNCs, CD34+ cells, colony‐forming units (CFUs), white blood cells (WBCs), nucleated red blood cells (NRBCs), and the total collection volume were compared between cases with primary and secondary Cesarean section.RESULTS: UCB obtained after a Cesarean section due to fetal distress has significantly higher numbers of TNCs, CD34+ cells, NRBCs, and WBCs compared to elective Cesarean section. Of the cases with secondary Cesarean section due to fetal distress, 67 percent resulted in UCB units with sufficient TNC numbers (≥80 × 107 TNCs) compared to 42 percent of the cases with primary Cesarean section.CONCLUSION: Fetal distress increases the number of hematopoietic stem cells mobilized into UCB. Particular effort should be made to collect UCB from newborns who experienced fetal distress.