bluuebunny/crossref_metadata_2025 huggingface dataset:
Mucosal Immunization with a Urease B DNA Vaccine Induces Innate and Cellular Immune Responses Against Helicobacter pylori
Authors: Hatzifoti Caterina , Roussel Yvonne , Harris Andrew G. , Wren Brendan W. , Morrow John W. , Bajaj‐Elliott Mona
Published: March 2006

Background:  Helicobacter pylori is recognized as a major risk factor for recurrent gastroduodenal inflammatory diseases and gastric adenocarcinoma. The high prevalence of H. pylori infection worldwide, the risks of side‐effects from antibiotic therapy, and increasing resistance to antibiotics are the main primers for the development of improved H. pylori vaccines. The antigenic potential of its urease enzyme, a critical virulence factor required for colonization of the gastric mucosa, has been demonstrated in animal and human studies. An important but controversial issue in H. pylori vaccine studies is the type of immune response required to control infection. A new approach in H. pylori vaccinology is the administration of DNA vaccines, which has included heat‐shock protein and catalase DNA vaccines.

Materials and Methods:  The H. pylori urease subunit B construct or vector alone was administered to mice via the intranasal route. Spleens and stomachs were examined on day 0 and weeks 3, 6, and 12 after immunization. Proliferation of spleen cells was assessed using the carboxyfluorescein diacetate succinimidyl ester‐based flow cytometry assay and cytokine secretion from cultured spleen cells was detected by ELISA, after stimulation with the urease subunit B recombinant antigen. Total RNA was isolated from stomach and spleen tissue and the expression of β‐defensin and cytokine genes was monitored by reverse transcription followed by polymerase chain reaction (RT‐PCR). Immunized mice were challenged with H. pylori and bacterial DNA quantified by TaqMan PCR.

Results:  The urease B subunit DNA vaccine increased INF‐γ secretion and splenocyte proliferation without inducing adverse effects in the spleen. Increase in gastric β‐defensin 1 and marked induction in local IL‐10 : IFN‐γ ratio up to 12 weeks post‐immunization suggest a potential role for local innate immune responses in protection at the site of infection. Although significant bacterial reduction in the stomachs of urease B subunit DNA‐immunized mice was observed, intermediate reduction was also noted in the vector group. Increased defensin expression and adjuvant effects of the cytosine preceding guanosine motifs may contribute to this phenomenon. Our data confirm that cytosine preceding guanosine motifs, even without coadministration with antigen, can reduce extracellular bacterial load.

Conclusions:  In this study, a DNA construct encoding the urease B subunit was assessed for its immune profile and its ability to reduce bacterial colonization in the murine stomach. Our studies suggest that local innate immune responses may play a greater role than previously supposed in limiting H. pylori colonization in the gastric mucosa.
Effects of Estradiol and Progesterone on Gastric Mucosal Response to Early Helicobacter pylori Infection in Female Gerbils
Authors: Saqui‐Salces Milena , Rocha‐Gutiérrez Brenda L. , Barrios‐Payán Jorge A. , Ruiz‐Palacios Guillermo , Camacho‐Arroyo Ignacio , Gamboa‐Dominguez Armando
Published: March 2006

Background:  Gender differences have been shown regarding the changes in the inflammatory response, gastrin secretion, and gastric acidity during Helicobacter pylori infection.

Aim:  To investigate the role of estradiol and progesterone in the changes of the gastric mucosa induced by H. pylori during the early stage of infection in female gerbils.

Materials and Methods: Thirty‐three adult ovariectomized female gerbils were infected with H. pylori (SS1); 7 days after infection they were treated with low and high doses of estradiol (50 and 250 µg/60 days pellet), progesterone (15 and 50 mg/60 days pellet) and vehicle. Non‐ovariectomized infected gerbils were used as control. Gerbils were euthanized after 6 weeks of infection. Histologic evaluation, immunohistochemical detection of proliferation cell nuclear antigen (PCNA), gastrin, and apoptosis by terminal deoxynucleotide nick end labeling (TUNEL) assay were performed. Positive cells for PCNA, TUNEL, and gastrin were counted in 10 oriented glands per animal. Two‐sided p = .05 was considered significant.

Results:  Estradiol‐treated groups showed more intense and extended acute and follicular gastritis compared to the vehicle group, whereas progesterone‐treated groups presented less gastritis than the other groups. Proliferation and apoptosis indexes were significantly lower in the vehicle group when compared with those of the control; both indexes were increased in the high‐dose estradiol and progesterone groups as compared with those of the vehicle. Grade I nonmetaplastic atrophy was observed in the vehicle and progesterone groups. The high‐dose progesterone group showed a significant reduction in the number of gastrin cells.

Conclusions:  Estradiol and progesterone participate in the gastric mucosal response to early H. pylori infection in gerbils.
Carbonation of Cl‐rich scapolite boudins in Skallen, East Antarctica: evidence for changing fluid condition in the continental crust
Authors: SATISH‐KUMAR M. , HERMANN J. , TSUNOGAE T. , OSANAI Y.
Published: March 2006

Spectacular reaction textures in poikiloblastic scapolitite boudins, within marbles in the continental crust exposed in the Lützow–Holm Complex, East Antarctica, provide insights into the changing fluid composition and movement of fluid along grain boundaries and fractures. Petrographic and geochemical features indicate scapolite formation under contrasting fluid compositions. Core composition of scapolite poikiloblasts (ScpI) are marialitic (Cl = 0.7 apfu) whereas rims in contact with biotite or clinopyroxene are meionite rich. Fine‐grained recrystallized equigranular scapolite (ScpII) shows prominent chemical zoning, with a marialitic core and a meionitic rim (Cl = 0.36 apfu). Scapolite poikiloblasts are traversed by ScpIII reaction zones along fractures with compositional gradients. Pure CO2 fluid inclusions are observed in healed fractures in scapolite poikiloblasts. These negative crystal‐shaped fluid inclusions are moderately dense, and are believed to be coeval with ScpIII formation at temperatures >600 °C and a minimum pressure of c. 3.8 kbar. Grain‐scale LA‐ICPMS studies on trace and rare earth elements on different textural types of scaplolites and a traverse through scapolite reaction zone with compositional gradient suggest a multistage fluid evolution history. ScpI developed in the presence of an internally buffered, brine‐rich fluid derived probably from an evaporite source during prograde to peak metamorphism. Recrystallization and grain size reduction occurred in the presence of an externally sourced carbonate (CaCO3)‐bearing fluid, resulting in the leaching of Cl, K, Rb and Ba from ScpI along fractures and grain boundaries. Movement of fluids was enhanced by micro‐fracturing during the transformation of ScpI to ScpIII. Fractures in fluorapatite are altered to chlorapatite proving evidence for the pathways of escaping Cl‐bearing fluids released from ScpI. The present study thus provides evidence for the usefulness of scapolite in fingerprinting changing volatile composition and trace element contents of fluids that percolate within the continental crust.
Preservation of evidence for prograde metamorphism in ultrahigh‐temperature, high‐pressure kyanite‐bearing granulites, South Harris, Scotland
Authors: HOLLIS J.A. , HARLEY S.L. , WHITE R.W. , CLARKE G.L.
Published: March 2006

Mineralogical and mineral chemical evidence for prograde metamorphism is rarely preserved in rocks that have reached ultrahigh‐temperature (UHT) conditions (>900 °C) because high diffusion and reaction rates erase evidence for earlier assemblages. The UHT, high‐pressure (HP) metasedimentary rocks of the Leverburgh belt of South Harris, Scotland, are unusual in that evidence for the prograde history is preserved, despite having reached temperatures of ∼955 °C or more. Two lithologies from the belt are investigated here and quantitatively modelled in the system NaO–CaO–K2O–FeO–MgO–Al2O3–SiO2–H2O: a garnet‐kyanite‐K‐feldspar‐quartz gneiss (XMg = 37, A/AFM = 0.41), and an orthopyroxene‐garnet‐kyanite‐K‐feldspar quartzite (XMg = 89 A/AFM = 0.68). The garnet‐kyanite gneiss contains garnet porphyroblasts that grew on the prograde path, and captured inclusion assemblages of biotite, sillimanite, plagioclase and quartz (<790 °C, <9.5 kbar). These porphyroblasts preserve spectacular calcium zonation features with an early growth pattern overgrown by high‐Ca rims formed during high‐P metamorphism in the kyanite stability field. In contrast, Fe‐Mg zonation in the same garnet porphyroblasts reflects retrograde re‐equilibration, as a result of the relatively faster diffusivity of these ions. Peak P–T are constrained by the occurrence of coexisting orthopyroxene and aluminosilicate in the quartzite. Orthopyroxene porphyroblasts [y(opx) = 0.17–0.22] contain sillimanite inclusions, indicative of maximum conditions of 955 ± 45 °C at 10.0 ± 1.5 kbar. Subsequently, orthopyroxene, kyanite, K‐feldspar and quartz developed in equilibrated textures, constraining the maximum pressure conditions to 12.5 ± 0.8 kbar at 905 ± 25 °C. P–T–X modelling reveals that the mineral assemblage orthopyroxene‐kyanite‐quartz is compositionally restricted to rocks of XMg > 84, consistent with its very rare occurrence in nature. The preservation of unusual high P–T mineral assemblages and chemical disequilibrium features in these UHT HP rocks is attributed to a rapid tectonometamorphic cycle involving arc subduction and terminating in exhumation.
Lack of Interactions between Breast Cancer Resistance Protein (BCRP/ABCG2) and Selected Antiepileptic Agents
Authors: Cerveny Lukas , Pavek Petr , Malakova Jana , Staud Frantisek , Fendrich Zdenek
Published: March 2006

Summary:  Purpose: Recent studies have indicated constitutive expression of efflux transporter, breast cancer resistance protein (BCRP, ABCG2), in endothelial cells of the blood–brain barrier (BBB). In epileptogenic brain tumors such as ganglioma, astrocytoma, anaplastic astrocytomas, or glioma multiforme, strong expression of BCRP in the microvasculature of the BBB was observed. Therefore it was hypothesized that this phenomenon could critically influence the bioavailability of drugs in these tumors and potentially contribute to the failure of antiepileptic treatment. The aim of this study was to test whether some commonly used antiepileptic drugs (AEDs) are substrates transported by human BCRP. In particular, we focused on phenobarbital, phenytoin, ethosuximide, primidone, valproate, carbamazepine, clonazepam, and lamotrigine. Furthermore, the inhibitory potency of these AEDs to BCRP was examined.

Methods: To study substrate affinity of tested AEDs to BCRP, transport experiments were performed in epithelial BCRP‐expressing MDCKII‐BCRP and MDCKII‐parent cell lines cultured on microporous membrane. For detection of inhibitory potency of AEDs to BCRP, accumulation assays were carried out in MEF3.8‐BCRP cells with known BCRP substrates, BODIPY FL prazosin and mitoxantrone.

Results: No obvious interactions of tested AEDs with BCRP transporter were observed. Therefore these drugs in relevant therapeutic concentrations are neither substrates nor inhibitors of BCRP.

Conclusions: Based on our in vitro data we can conclude that resistance to treatment with the tested AEDs probably is not caused by the overexpression of BCRP in the BBB of epileptogenic brain tumors.
Beta and Gamma Range EEG Power‐Spectrum Correlation with Spiking Discharges in DBA/2J Mice Absence Model: Role of GABAB Receptors
Authors: Marrosu Francesco , Santoni Federico , Fà Mauro , Puligheddu Monica , Barberini Luigi , Genugu Fabrizio , Frau Roberto , Manunta Mario , Mereu Giampaolo
Published: March 2006

Summary:  Purpose: To describe the correlations between spiking pattern and EEG power spectrum frequency in DBA/2J mice, a model for murine absence seizures, after γ‐aminobutyric acid (GABA)B modulation.

Methods: The animals were first tested with the GABAB agonist l‐baclofen followed by the GABAB antagonist SCH 50911. Moreover, digital EEGs recorded under experimental conditions were processed at baseline and 10 and 20 min after l‐baclofen injection. This procedure was followed by injection of the GABAB antagonist SCH50911 and by an additional EEG evaluation at 10 and 20 min from drug administration. The power spectra analysis of signals was obtained for delta (0.5–3 Hz), theta (3.5–7.5 Hz), alpha (8–12 Hz), beta (13–20 Hz), and gamma (21–50 Hz) frequencies.

Results: The spiking pattern and power spectrum of beta activity was increased by ≤80% after administration of 5 mg/kg l‐baclofen, whereas gamma power frequency decreased to the same extent. After administration of 50 mg/kg SCH 50911, spiking activity and beta power frequencies were markedly reduced (>80%), whereas gamma power increased (correlation, 0.92; p < 0.001). The remaining frequency bands were unaffected.

Conclusions: This study confirms the potential of GABAB antagonists in contrasting seizure absence in rodent models and suggests the application of drugs with a similar mechanism in humans. In addition, because GABAB antagonists not only contrast seizure in rodent models of absence but also improve “cognitive” performance, it could be hypothesized that gamma increase, correlated with optimized cortical binding during coherent percepts, may produce potential cognition‐enhancing effects.
Brain Homocarnosine and Seizure Control of Patients Taking Gabapentin or Topiramate
Authors: Petroff Ognen A. C. , Hyder Fahmeed , Rothman Douglas L. , Mattson Richard H.
Published: March 2006

Summary:  Purpose: To assess the relation between seizure control and brain homocarnosine and γ‐aminobutyric acid (GABA) levels of patients with complex partial seizures taking gabapentin (GBP) or topiramate (TPM) as adjunctive therapy.

Methods: In vivo measurements of GABA and homocarnosine were made of a 14‐cc volume in the occipital cortex by using 1H spectroscopy with a 2.1‐Tesla magnetic resonance spectrometer and an 8‐cm surface coil. Poor seizure control was defined as more recent seizures than the median for the two groups of patients studied.

Results: Homocarnosine levels were higher in patients with better seizure control than in those with poor control. No differences were found in the intracellular GABA levels between the patients who responded to GBP or TPM compared with those who did not.

Conclusions: In the visual neocortex, which is remote from the presumed seizure‐onset zone, higher homocarnosine levels were associated with better seizure control in the patients taking GBP or TPM as adjunctive therapy; elevated intracellular GABA levels appeared to offer no additional protection.
Suppressive Efficacy by a Commercially Available Blue Lens on PPR in 610 Photosensitive Epilepsy Patients
Authors: Capovilla Giuseppe , Gambardella Antonio , Rubboli Guido , Beccaria Francesca , Montagnini Alessandra , Aguglia Umberto , Canevini Maria Paola , Casellato Susanna , Granata Tiziana , Paladin Francesco , Romeo Antonino , Stranci Giuseppe , Tinuper Paolo , Veggiotti Pierangelo , Avanzini Giuliano , Tassinari Carlo Alberto
Published: March 2006

Summary:  Purpose: Photosensitivity can represent a serious problem in epilepsy patients, also because pharmacologic treatment is often ineffective. Nonpharmacologic treatment using blue sunglasses is effective and safe in controlling photosensitivity, but large series of patients have never been studied.

Methods: This multicenter study was conducted in 12 epilepsy centers in northern, central, southern, and insular Italy. A commercially available lens, named Z1, obtained in a previous trial, was used to test consecutively enrolled pediatric and adult epilepsy patients with photosensitivity. Only type 4 photosensitivity (photoparoxysmal response, PPR) was considered in the study. A standardized method was used for photostimulation.

Results: Six hundred ten epilepsy patients were tested. Four hundred (66%) were female patients; 396 (65%) were younger than 14 years. Three hundred eighty‐one (62%) subjects were pharmacologically treated at the time of investigation. Z1 lenses made PPR disappear in 463 (75.9%) patients, and PPR was considerably reduced in an additional 109 (17.9%) of them. PPR remained unchanged only in the remaining 38 (6.2%) patients. The response of PPR to Z1 lenses was not significantly influenced by the patients' age, sex, or type of epilepsy. No difference was found between pharmacologically treated and untreated patients.

Conclusions: The Z1 lens is highly effective in controlling PPR in a very large number of photosensitive epilepsy patients irrespective of their epilepsy or antiepileptic drug treatment. The lens might become a valid resource in the daily activity of any clinician who cares for patients with epilepsy.
Role ofSOX2Mutations in Human Hippocampal Malformations and Epilepsy
Authors: Sisodiya Sanjay M. , Ragge Nicola K. , Cavalleri Gianpiero L. , Hever Ann , Lorenz Birgit , Schneider Adele , Williamson Kathleen A. , Stevens John M. , Free Samantha L. , Thompson Pamela J. , Van Heyningen Veronica , FitzPatrick David R.
Published: March 2006

Summary: Purpose:Seizures are noted in a significant proportion of cases of de novo, heterozygous, loss‐of‐function mutations inSOX2,ascertained because of severe bilateral eye malformations. We wished to determine the underlying cerebral phenotype inSOX2mutation and to test the candidacy ofSOX2as a gene contributing to human epilepsies.

Methods:We examined high‐resolution MRI scans in four patients withSOX2mutations, two of whom had seizures. We determined theSox2expression pattern in developing murine brain. We searched forSOX2mutation in 24 patients with typical hippocampal sclerosis and for common variations inSOX2in 655 patients without eye disease but with epilepsy, including 91 patients with febrile seizures, 93 with hippocampal sclerosis, and 258 with temporal lobe epilepsy.

Results:Striking hippocampal and parahippocampal malformations were seen in all cases, with a history of febrile seizures or epilepsy in two of four cases. TheSox2expression pattern in developing mouse brain supports the pattern of malformations observed. Mutation screening in patients with epilepsy did not reveal any abnormalities inSOX2. No associations were found between any clinical epilepsy phenotype and common variation inSOX2.

Conclusions: SOX2haploinsufficiency causes mesial temporal malformation in humans, makingSOX2dysfunction a candidate mechanism for mesial temporal abnormalities associated with chronic epilepsy. However, although mutation ofSOX2in humans causes hippocampal malformation,SOX2mutation or variation is unlikely to contribute commonly to mesial temporal lobe epilepsy or its structural (hippocampal sclerosis) or historic (febrile seizures) associations in humans.
Analyzing the Etiology of Benign Rolandic Epilepsy: A Multicenter Twin Collaboration
Authors: Vadlamudi Lata , Kjeldsen Marianne J. , Corey Linda A. , Solaas Marit H. , Friis Mogen L. , Pellock John M. , Nakken Karl O. , Milne Roger L. , Scheffer Ingrid E. , Harvey A. Simon , Hopper John L. , Berkovic Samuel F.
Published: March 2006

Summary:  Purpose: Benign rolandic epilepsy (BRE) is considered a genetically determined idiopathic partial epilepsy. We analyzed a large sample of twins from four international twin registers to probe the genetics of BRE. We also aim to synthesize the apparently conflicting family and twin data into a model of BRE etiology.

Methods: Large population‐based twin registries of epilepsies from Odense (Denmark), Richmond, Virginia (United States), and Oslo (Norway) were reviewed for BRE cases and added to our Australian twin data. Diagnosis of classic BRE was based on electroclinical criteria with normal neurologic development. Cases with a compatible electroclinical picture but abnormal neurologic development were termed nonclassic BRE.

Results: Eighteen twin pairs were identified (10 monozygous; eight dizygous) of whom at least one twin was diagnosed with classic BRE among a total sample of 1,952 twin pairs validated for seizures, and all were discordant for BRE. The estimated monozygous pairwise concordance for BRE in this sample was 0.0 [95% confidence interval (CI), 0.0–0.3). Four twin pairs (one monozygous, three dizygous) had nonclassic BRE, and all co‐twins had seizures.

Conclusions: The twin data showing an absence of any concordant twin pairs with classic BRE suggest that noninherited factors are of major importance in BRE. Modelling the data shows that the familial occurrence of centrotemporal spikes makes only a minor contribution to the familial aggregation of BRE. Genetic factors are probably more important in nonclassic BRE. The etiology and mode(s) of inheritance of BRE are much more complicated than initially conceptualized.
Seizure Outcome after Resection of Cavernous Malformations Is Better When Surrounding Hemosiderin‐stained Brain Also Is Removed
Authors: Baumann Christian R. , Schuknecht Bernhard , Lo Russo Giorgio , Cossu Massimo , Citterio Alberto , Andermann Frederick , Siegel Adrian M.
Published: March 2006

Summary:  Purpose: Considering the epileptogenic effect of cavernoma‐surrounding hemosiderin, assumptions are made that resection only of the cavernoma itself may not be sufficient as treatment of symptomatic epilepsy in patients with cavernous malformations. The purpose of this study was to test the hypothesis whether seizure outcome after removal of cavernous malformations may be related to the extent of resection of surrounding hemosiderin‐stained brain tissue.

Methods: In this retrospective study, 31 consecutive patients with pharmacotherapy‐refractory epilepsy due to a cavernous malformation were included. In all patients, cavernomas were resected, and all patients underwent pre‐ and postoperative magnetic resonance imaging (MRI). We grouped patients according to MRI findings (hemosiderin completely removed versus not/partially removed) and compared seizure outcome (as assessed by the Engel Outcome Classification score) between the two groups.

Results: Three years after resection of cavernomas, patients in whom hemosiderin‐stained brain tissue had been removed completely had a better chance for a favorable long‐term seizure outcome compared with those with detectable postoperative hemosiderin (p = 0.037).

Conclusions: Our study suggests that complete removal of cavernoma‐surrounding hemosiderin‐stained brain tissue may improve epileptic outcome after resection of cavernous malformations.
Prognostic Factors in Neocortical Epilepsy Surgery: Multivariate Analysis
Authors: Yun Chang‐Ho , Lee Sang Kun , Lee Seo Young , Kim Kwang Ki , Jeong Sang Wook , Chung Chun‐Ki
Published: March 2006

Summary:  Purpose: Defining prognostic factors for neocortical epilepsy surgery is important for the identification of ideal candidates and for predicting the prognosis of individual patients. We use multivariate analysis to identify favorable prognostic factors for neocortical epilepsy surgery.

Methods: One hundred ninety‐three neocortical epilepsy patients, including 91 without focal lesions on MRI, were included. Sixty‐one had frontal lobe epilepsy (FLE), 80 had neocortical temporal lobe epilepsy (nTLE), 21 had parietal lobe epilepsy (PLE), and 22 had occipital lobe epilepsy (OLE). The primary outcome variable was patient status ≥2 years after surgery (i.e., seizure free or not). Clinical characteristics and the recent presurgical diagnostic modalities were considered as probable prognostic factors. Univariate and standard multiple logistic regression analyses were used to identify favorable prognostic factors.

Results: The seizure‐free rate was 57.5%. By univariate analysis, a focal lesion on MRI, localized ictal onset on surface EEG, epilepsies other than FLE, localized hypometabolism on fluorodeoxyglucose–positron emission tomography (FDG‐PET), and pathologies other than cortical dysplasia were significantly associated with a seizure‐free outcome (p < 0.05). Multivariate analysis revealed that a focal lesion on MRI (p = 0.003), correct localization by FDG‐PET (p = 0.007), and localized ictal onset on EEG (p = 0.01) were independent predictors of a good outcome.

Conclusions: The presence of a focal lesion on MRI, correct localized hypometabolism on FDG‐PET, or localized ictal rhythms on EEG were identified as predictors of a seizure‐free outcome. Our results suggest that these findings allow the selection of better candidates for neocortical epilepsy surgery.
Autonomic Symptoms during Childhood Partial Epileptic Seizures
Authors: Fogarasi András , Janszky József , Tuxhorn Ingrid
Published: March 2006

Summary: Purpose:To analyze systematically the occurrence and age dependence as well as the localizing and lateralizing value of ictal autonomic symptoms (ASs) during childhood partial epilepsies and to compare our results with those of earlier adult studies.

Methods:Five hundred fourteen video‐recorded seizures of 100 consecutive children 12 years or younger with partial epilepsy and seizure‐free postoperative outcome were retrospectively analyzed.

Results:Sixty patients produced at least one AS; 43 (70%) of 61 with temporal and 17 (44%) of 39 with extratemporal lobe epilepsy (p = 0.012). Apnea/bradypnea occurred more frequently in younger children (p < 0.01), whereas the presence of other ASs was neither age nor gender related. Postictal coughing (p < 0.01) and epigastric aura (p < 0.05) localized to the temporal lobe, whereas no ASs lateralized to the seizure‐onset zone.

Conclusions:Our study shows that ASs are common in childhood focal epilepsies, appearing in infants and young children, too. As in adults, childhood central autonomic networks might have a close connection to temporal lobe structures but do not lateralize the seizure‐onset zone. To our knowledge, this is the first study comprehensively assessing ASs in childhood epilepsy.
Language and Motor fMRI Activation in Polymicrogyric Cortex
Authors: Araujo David , De Araujo Draulio B. , Pontes‐Neto Octavio M. , Escorsi‐Rosset Sara , Simao Gustavo N. , Wichert‐Ana Lauro , Velasco Tonicarlo R. , Sakamoto Americo C. , Leite Joao P. , Santos Antonio C.
Published: March 2006

Summary:  Purpose: To analyze the patterns of brain activation in polymicrogyric cortex in epilepsy patients by blood oxygenation level–dependent (BOLD) functional MRI (fMRI), during language and motor activation tasks.

Methods: Five patients with extratemporal epilepsy associated with polymicrogyria were scanned in a 1.5‐T Siemens scanner with BOLD fMRI sequences, by following language and motor paradigms. Functional images were processed by using Brain Voyager software.

Results: Activation of polymicrogyric cortex in the brain area that corresponds to the motor strip was present in all patients. Language studies revealed activation of polymicrogyric cortex over Broca's area in three cases.

Conclusions: Functionality was shown in polymicrogyric areas. Therefore if surgical resection is indicated, a careful functional planning is necessary because of functionality of the polymicrogyric cortex.
fMRI Shows Atypical Language Lateralization in Pediatric Epilepsy Patients
Authors: Yuan Weihong , Szaflarski Jerzy P. , Schmithorst Vincent J. , Schapiro Mark , Byars Anna W. , Strawsburg Richard H. , Holland Scott K.
Published: March 2006

Summary:  Purpose: The goal of this study was to compare language lateralization between pediatric epilepsy patients and healthy children.

Methods: Two groups of subjects were evaluated with functional magnetic resonance imaging (fMRI) by using a silent verb‐generation task. The first group included 18 pediatric epilepsy patients, whereas the control group consisted of 18 age/gender/handedness‐matched healthy subjects.

Results: A significant difference in hemispheric lateralization index (LI) was found between children with epilepsy (mean LI =−0.038) and the age/gender/handedness–matched healthy control subjects (mean LI = 0.257; t = 6.490, p < 0.0001). A dramatic difference also was observed in the percentage of children with epilepsy (77.78%) who had atypical LI (right‐hemispheric or bilateral, LI < 0.1) when compared with the age/gender/handedness‐matched group (11.11%; χ2= 16.02, p < 0.001). A linear regression analysis showed a trend toward increasing language lateralization with age in healthy controls (R2= 0.152; p = 0.108). This association was not observed in pediatric epilepsy subjects (R2= 0.004, p = 0.80). A significant association between language LI and epilepsy duration also was found (R2= 0.234, p < 0.05).

Conclusions: This study shows that epilepsy during childhood is associated with neuroplasticity and reorganization of language function.
Family Predictors of Psychopathology in Children with Epilepsy
Authors: Rodenburg Roos , Marie Meijer Anne , Deković Maja , Aldenkamp Albert P.
Published: March 2006

Summary: Purpose:To examine the contribution of epilepsy‐related factors, proximal (parent–child relationship quality), distal (parental characteristics), and contextual (quality of other family relationships) family factors to psychopathology (both broad‐band and narrow‐band syndromes) in children with epilepsy and normal intelligence.

Methods:Parents of 91 children (mean, 8.5 years) participated by filling out questionnaires about family factors and child psychopathology. Regression analyses were used to analyze the unique and combined predictive power of family factors in relation to psychopathology.

Results:In contrast to epilepsy‐related factors, family factors, especially those related to the quality of the parent–child relationship, appeared to be strong predictors of psychopathology. The results supported the mediational model: Distal and contextual factors affect child psychopathology by affecting proximal factors.

Conclusions:In treating children with epilepsy, clinicians should be aware of the importance of the parent–child relationship quality. Strengthening the relationship quality may prevent or reduce psychopathology.
Physical Activity in Children/Teens with Epilepsy Compared with That in Their Siblings without Epilepsy
Authors: Wong Judy , Wirrell Elaine
Published: March 2006

Summary:  Purpose: To determine (a) whether children and teens with epilepsy participate in less physical activity and have higher body mass index (BMI) percentiles for age than do their siblings without epilepsy; and (b) what epilepsy‐specific factors limit their participation.

Methods: Patients 5–17 years, with a ≥3 month history of epilepsy, a development quotient ≥80, no major motor or sensory impairments, and at least one sibling without epilepsy in a similar age range, were identified from the Neurology Clinic database or at the time of clinic visit. Parents completed a questionnaire regarding sedentary activities and group, individual, and total sports activities. Children aged 11–15 years also completed the physical activity portion of the Health Behavior in School Aged Children questionnaire. Clinic charts were reviewed for seizure type, etiology, frequency, duration of epilepsy, and number of antiepileptic drugs (AEDs) ever taken.

Results: Teens with epilepsy participated in fewer group and total sports activities than did controls and were more likely to be potentially overweight or overweight. Receiving three or more AEDs in the past showed a significant negative correlation with sports participation. Although a trend was noted for those with higher seizure frequency to be less active, no other epilepsy‐specific factors or prior seizures or seizure‐related injury during a sports event correlated with participation in physical activity.

Conclusions: Programs that promote exercise in adolescents with epilepsy should be encouraged to improve their physical, psychological, and social well‐being.
Clinical and Genetic Findings in 26 Italian Patients with Lafora Disease
Authors: Franceschetti Silvana , Gambardella Antonio , Canafoglia Laura , Striano Pasquale , Lohi Hannes , Gennaro Elena , Ianzano Leonarda , Veggiotti Pierangelo , Sofia Vito , Biondi Roberto , Striano Salvatore , Gellera Cinzia , Annesi Grazia , Madia Francesca , Civitelli Donata , Rocca Francesca E. , Quattrone Aldo , Avanzini Giuliano , Minassian Berge , Zara Federico
Published: March 2006

Summary:  Purpose:
EPM2B mutations have been found in a variable proportion of patients with Lafora disease (LD). Genotype–phenotype correlations suggested that EPM2B patients show a slower course of the disease, with delayed age at death, compared with EPM2A patients. We herein report clinical and genetic findings of 26 Italian LD patients.

Methods: Disease progression was evaluated by means of a disability scale based on residual motor and cognitive functions and daily living and social abilities, at 4 years from the onset. Mutational analysis was performed by sequencing the coding regions of the EPM2A and EPM2B genes.

Results: Age at onset ranged from 8.5 to 18.5 years (mean, 13.7 ± 2.6). The mean duration of follow‐up was 7.1 ± 3.9 years. Daily living activities and social interactions were preserved in five of 24 patients. The remaining patients showed moderate to extremely severe limitations of daily living and social abilities. Sixteen (72%) of 22 families showed mutations in the EPM2B gene, and five (22%), in the EPM2A gene. One family showed no mutations. A novel EPM2B mutation also was identified.

Conclusions: In our series, EPM2B mutations occurred in 72% of families, thus indicating that EPM2B is the major gene for LD in the Italian population. Moreover, we found that six of 17 EPM2B patients preserved daily living activities and social interactions at 4 years from onset, suggesting a slow disease progression. Additional clinical and functional studies will clarify whether specific mutations may influence the course of the disease in LD patients.
Socrates and Temporal Lobe Epilepsy: A Pathographic Diagnosis 2,400 Years Later
Authors: Muramoto Osamu , Englert Walter G.
Published: March 2006

Summary:  Purpose: Some enigmatic remarks and behaviors of Socrates have been a subject of debate among scholars. We investigated the possibility of underlying epilepsy in Socrates by analyzing pathographic evidence in ancient literature from the viewpoint of the current understanding of seizure semiology.

Methods: We performed a case study from a literature survey.

Results: In 399 BCE, Socrates was tried and executed in Athens on the charge of “impiety.” His charges included the “introduction of new deities” and “not believing in the gods of the state,” because he publicly claimed that he was periodically and personally receiving a “divine sign,” or daimonion, that directed him in various actions. We found textual evidence that his daimonion was probably a simple partial seizure (SPS) of temporal lobe origin. It was a brief voice that usually prohibited Socrates from initiating certain actions. It started when he was a child, and it visited Socrates unpredictably. Moreover, we found at least two descriptions of Socrates' unique behavior that are consistent with complex partial seizures (CPSs). The fact that Socrates had been experiencing both SPSs and CPSs periodically since childhood makes the diagnosis of temporal lobe epilepsy (TLE) likely.

Conclusions: We hypothesize that Socrates had a mild case of TLE without secondary generalization. This is the first report in 2,400 years to present a pathographic diagnosis of TLE in Socrates based on specific diagnostic features in the ancient textual evidence. Our study demonstrates that the knowledge of modern epileptology could help understand certain behaviors of historic figures.
The Public Pension Reform Debate in the United States and International Experience
Authors: Diamond Peter A.
Published: March 2006

Abstract

This article describes the recent debate on Social Security in the United States. To provide some perspectives on the U.S. system, comparisons with public pension systems in other countries are made throughout the article. The article is organized as follows. The first section discusses financing problems in the U.S. Social Security system. Following this, the U.S. Social Security system is described. Options for fixing public pension systems are discussed next. The topic of individual accounts appears in its own section.
Bayesian Dose‐Finding in Phase I/II Clinical Trials Using Toxicity and Efficacy Odds Ratios
Authors: Yin Guosheng , Li Yisheng , Ji Yuan
Published: March 2006

Summary A Bayesian adaptive design is proposed for dose‐finding in phase I/II clinical trials to incorporate the bivariate outcomes, toxicity and efficacy, of a new treatment. Without specifying any parametric functional form for the drug dose–response curve, we jointly model the bivariate binary data to account for the correlation between toxicity and efficacy. After observing all the responses of each cohort of patients, the dosage for the next cohort is escalated, deescalated, or unchanged according to the proposed odds ratio criteria constructed from the posterior toxicity and efficacy probabilities. A novel class of prior distributions is proposed through logit transformations which implicitly imposes a monotonic constraint on dose toxicity probabilities and correlates the probabilities of the bivariate outcomes. We conduct simulation studies to evaluate the operating characteristics of the proposed method. Under various scenarios, the new Bayesian design based on the toxicity–efficacy odds ratio trade‐offs exhibits good properties and treats most patients at the desirable dose levels. The method is illustrated with a real trial design for a breast medical oncology study.
A Proposal for Standardization in Forensic Canine DNA Typing: Allele Nomenclature of Six Canine‐Specific STR Loci
Authors: Hellmann Andreas P. , Rohleder Udo , Eichmann Cordula , Pfeiffer Ina , Parson Walther , Schleenbecker Uwe
Published: March 2006

ABSTRACT: In this study a proposal for the allele nomenclature of six polymorphic short tandem repeat (STR) loci (PEZ3, PEZ6, PEZ8, PEZ10, FHC2161, and FHC2328) for canine genotyping (Canis lupus familiaris) is presented. The nomenclature is based on the sequence data of the polymorphic region of the microsatellite markers as recommended by the DNA commission of the International Society of Forensic Haemogenetics (ISFH) in 1994 for human DNA typing. To cover commonly and rarely occurring alleles, a selection of homozygous and heterozygous animals were analyzed and subjected to sequence studies. The alleles consisted of simple tri‐ and tetra‐nucleotide repeat patterns as well as compound and highly complex repeat patterns. Several alleles revealing the same fragment size but different repeat structures were found. The allele designation described here was adopted to the number of repeats, including all variable regions within the amplified fragment. In a second step the most commonly occurring alleles were added to an allelic ladder for each marker allowing a reliable typing of all alleles differing in size. A total number of 142 unrelated dogs from surrounding municipal animal homes, private households, and canines in police duty were analyzed. The data were added to a population database providing allele frequencies for each marker.
Color Analysis of Apparently Achromatic Automotive Paints by Visible Microspectrophotometry
Authors: Kopchick Kristin A. , Bommarito Christopher R.
Published: March 2006

ABSTRACT: Chromatic secondary pigments are utilized in achromatic automotive paints to create unique paint systems. These pigments may not be observable in reflected light; however, utilizing visible microspectrophotometry (MSP) discriminating data may be gathered. This study analyzed 160 apparently achromatic automotive paints via this technique for spectral evidence of secondary pigmentation. These results were compared with visual observations made via polarizing light microscopy. Positive spectral results were attained in approximately 25% of the black and gray/silver topcoat sample sets, whereas the white topcoat and gray undercoat set yielded no probative spectral data. The black sample set did yield several samples that produced spectral evidence of pigmentation when no visual chromatic data was observed. The results of this study suggest that paint analysis schemes should incorporate visible MSP for apparently achromatic black and gray/silver paint samples.
Identification of a Novel Polymorphism in the X‐Chromosome Region Homologous to the DYS456 Locus
Authors: Chang Chien‐Wei , Mulero Julio J. , Budowle Bruce , Calandro Lisa M. , Hennessy Lori K.
Published: March 2006

ABSTRACT: During an extensive multipopulation study with Y‐short tandem repeat (STR) loci, amplified using the AmpFℓSTR® Yfiler™ PCR amplification kit, amplification of a 71 bp fragment was observed in 2.32% of the male samples analyzed (N=3141). By direct sequencing of this fragment, it was determined that the primer binding sequences were identical to those of the DYS456 locus. A T to G single‐nucleotide polymorphism (SNP) enabled amplification of the 71 bp fragment. The SNP is located within an X–Y homologous region at Xq21.31 and was observed with the highest frequency within the African American and Sub‐Saharan African populations in our study. Presence of SNP on the X chromosome did not interfere with the reliability of typing the DYS456 locus and the other Y‐STR loci typeable using the AmpFℓSTR® Yfiler™ PCR amplification kit. Full profiles in a mixture of male:female at 1:4000 were obtained using the current configuration of the AmpFℓSTR Yfiler kit even in the presence of female DNA containing the G variant.
Sudden Death Due to an Unrecognized Cardiac Hydatid Cyst: Three Medicolegal Autopsy Cases
Authors: Pakis Isil , Akyildiz Elif Ulker , Karayel Ferah , Turan Arzu Akcay , Senel Berna , Ozbay Mehmet , Cetin Gursel
Published: March 2006

ABSTRACT: Echinococcosis is a human infection caused by the larval stage of Echinococcocus granulosus. The most common sites of infection are the liver and the lungs. Cardiac hydatid cysts are very rare, even in regions where hydatic cysts are endemic (the Mediterranean, South America, Africa, and Australia). It has been reported that cardiac involvement is seen in about 0.5–3% of human echinococcosis cases. Three cases of cardiac hydatid disease that caused sudden death and which were histopathologically diagnosed are reported. Cardiac echinococcosis is rare, but due to its insidious presentation and affinity to cause sudden death, it is important that it be identified in the histopathological examination.
Minisequencing‐Based Genotyping of Duffy and ABO Blood Groups for Forensic Purposes
Authors: Ferri Gianmarco , Bini Carla , Ceccardi Stefania , Ingravallo Francesca , Lugaresi Federica , Pelotti Susi
Published: March 2006

ABSTRACT: Duffy and ABO blood group genetic polymorphisms were studied by minisequencing analysis of single‐nucleotide polymorphisms (SNPs) at nucleotide positions—33, 125, 265, and 298 of the Duffy gene and at nucleotide positions—261, 297, 467, 646, and 703 of the ABO gene. In an Italian population sample, we found four alleles and seven genotypes for the Duffy and six alleles and 16 genotypes for the ABO systems. The lower limit for reproducible results was 200 pg DNA, with a range of up to 10 ng and an optimum at 1 ng. All of the 16 analyzed inclusive paternity tests were also consistent with parentage and two out of four inconsistencies with parentage cases were excluded by one or more SNPs. Although Duffy and ABO SNP typing show lower informativeness than most current forensic tests, their robustness, the limited population distribution of FY*Fy type, and the sensitivity of the minisequencing technology suggest that these markers can be useful in selected forensic applications.
Pediatric Homicides Related to Burn Injury: A Retrospective Review at the Medical University of South Carolina
Authors: Zaloga William F. , Collins Kim A.
Published: March 2006

ABSTRACT: Many burn injuries are mistakenly referred to as “accidents” because they occur suddenly and seem unpredictable and uncontrollable; however, injuries often occur in predictable patterns. We reviewed all pediatric forensic cases referred to the Medical University of South Carolina Forensic Pathology Section over a 28‐year period from January 1975 to December 2002. There were 124 cases with 121 fire‐related fatalities and three scald fatalities. Ninety of the burn victims were in the 0–5‐year age group. The manner of deaths showed 108 accidents and 12 homicides (four undetermined). Eleven of 12 burn‐related homicides occurred at the home with all of the victims in the 1–8‐year age group. The perpetrator of the home fire homicides was the mother in five cases and the sister in one case (two undetermined). Homicide involved a vehicle fire in one case in which the father caused an explosion with an accelerant. The three scald death perpetrators were the father, mother's boyfriend, and an aunt.This retrospective study and review of the literature may reveal patterns useful for evaluation of manner of death. By recognizing scene characteristics, potential perpetrators, and children at risk, we can better classify pediatric burn‐related fatalities.
The Influence of Site of Collection on Postmortem Morphine Concentrations in Heroin Overdose Victims
Authors: Crandall Cameron S. , Kerrigan Sarah , Agüero Blau Roberto L. , LaValley Jonathon , Zumwalt Ross , McKinney Patrick E.
Published: March 2006

ABSTRACT: When assaying for postmortem morphine concentration, significant site sampling variability exists between central and peripheral sampling sites and even within sampling regions of the body. To study the variation, 76 suspected heroin overdoses were identified. Each had femoral artery (FA) and vein (FV), left and right ventricle and pooled heart blood samples obtained at autopsy. Forty‐four tested positive for morphine. Morphine concentrations were determined by gas chromatography/mass spectrometry, with sampling site differences reported as log‐transformed ratios and compared by signed rank test.The mean FA to FV ratio for total morphine was 1.2 (range 0–4.5). The ratio for left heart to right heart total morphine was 1.1 (range 0.4–3.2). Left ventricular to FV total morphine ratio was 2.0 (range 0.6–6.9). In these opioid overdose deaths, FA and FV morphine concentrations are usually similar, although up to 4.5‐fold differences were noted. Centrally obtained morphine concentrations are on average twice as high compared with peripheral morphine concentrations. Left and right ventricular morphine concentrations were usually similar, although up to 3.2‐fold differences were noted (left side higher).
Esophageal Causes of Sudden and Unexpected Death
Authors: Byard Roger W.
Published: March 2006

ABSTRACT: Gastrointestinal conditions are uncommon causes of sudden and/or unexpected death as compared to cardiovascular diseases, motor vehicle trauma, or suicide, and may involve an array of fatal mechanisms. Lethal esophageal conditions are encountered even less often, the manifestations of which include acute upper airway occlusion from tumors or foreign material, intraluminal hemorrhage from vascular abnormalities, or perforation with fistula formation resulting in hemorrhage and sepsis. When encountered at autopsy, a particular condition may also be a manifestation of a disease that does not primarily involve the esophagus. For this reason, a detailed autopsy investigation is required for evidence of systemic or remote disease when lesions are found within the esophagus. In this report, possible life‐threatening esophageal conditions are reviewed with a description of lethal mechanisms, mention of rare associated diseases, and comment on difficulties that may arise at autopsy in the evaluation of such cases.