bluuebunny/crossref_metadata_2025 huggingface dataset:
Discovery of the hepatitis C virus
Authors: Houghton Michael
Published: January 2009

After nearly 6 years of intensive investigations between 1982 and 1988 in my laboratory at Chiron corporation, in which numerous molecular biological methods were used to investigate the viral aetiology of parenterally transmitted non‐A, non‐B viral hepatitis (NANBH), a single cDNA clone (5‐1‐1) was isolated that was shown to be derived from a new flavi‐like virus, termed the hepatitis C virus (HCV). After screening hundreds of millions of bacterial cDNA clones derived from different liver and plasma samples obtained from experimentally infected chimpanzees, a single HCV clone was eventually isolated using a novel, blind immunoscreening method in which antibodies derived from a clinically diagnosed NANBH patient were used to identify a cDNA clone encoding an immunodominant epitope within HCV nonstructural protein 4. Its viral origin was demonstrated by its specific hybridization to a large single‐stranded RNA molecule of ∼10 000 nucleotides found only in NANBH‐infected samples that shared distant sequence identity with flaviviruses. Further, HCV clone 5‐1‐1 was shown to be extrachromosomal and to encode an antigen eliciting antibody seroconversion only in NANBH‐infected chimpanzees and humans. Subsequent work demonstrated that HCV was the principal cause of parenterally transmitted NANBH around the world, with an estimated 170 million global carriers and that blood screening tests detecting circulating HCV antibodies and viral RNA could effectively eradicate the transmission of transfusion‐associated NANBH. Key viral‐encoded enzymes essential to its life cycle are now the targets of vigorous, ongoing drug development activities, and the feasibility of successful vaccination strategies has been demonstrated using the valuable chimpanzee model, without which any progress on HCV would not have been possible. My colleagues and coworkers who made essential contributions to the discovery of HCV were George Kuo, who had his own laboratory at Chiron and who provided intellectual and practical input, Dan Bradley of the Centers for Disease Control and Prevention, who provided a large supply of well‐characterized chimpanzee samples and knowledge of the NANBH field, and Qui‐Lim Choo, in my own laboratory, who provided many years of outstandingly dedicated and precise molecular biology expertise.
HBeAg‐negative chronic hepatitis B: why do I treat my patients with nucleos(t)ide analogues
Authors: Lampertico Pietro , Colombo Massimo
Published: January 2009

Antiviral therapy is aimed to persistently suppress hepatitis B virus (HBV) to prevent liver complications and improve survival and long‐term administration of nucleos(t)ide analogues represents an attractive treatment strategy.

Five oral analogues are available, and all inhibit viral replication in most patients during the first year of therapy. By converse, long‐term monotherapy is associated to high rates of resistance with lamivudine, and intermediate rates with Adefovir and Telbivudine. Third‐generation analogues such as Entecavir and Tenofovir may efficiently inhibits viral replication in most patient for many years as they couple potency and high genetic barrier. In patients developing drug‐resistance, specific rescue protocols based upon ‘early add‐on’ have been developed to rapidly and efficiently control viral replication. In cirrhotics, long‐term effective analog‐based therapy prevented clinical decompensation for many years, but not liver cancer development. Long‐term administration of NUCs, either as a monotherapy or as a sequential combination, inhibits HBV replication in most HBeAg‐negative patients for at least 5 years, preventing clinical decompensation in cirrhotics.
Hepatitis B and pregnancy: an underestimated issue
Authors: Jonas Maureen M.
Published: January 2009

Hepatitis B infection during pregnancy presents a unique set of management issues. Aspects of care that must be considered include maternal and fetal effects of hepatitis B, effects of pregnancy itself on the course of hepatitis B infection and its complications, treatment of hepatitis B during pregnancy and prevention of perinatal infection. There are insufficient studies to date regarding these concerns; most are from the Far East, and many have important limitations, but some have yielded valuable data. Pregnant women with acute hepatitis B virus (HBV) infection typically have a course not very different from that in the general adult population, but the risk of transmission of HBV to neonates increases the later in gestation the acute infection occurs. Chronic HBV infection is usually mild in pregnant women, but may flare shortly after delivery. The risk of perinatal transmission is highest in women with high levels of viraemia; this may be a factor in the small but reproducible failure rate of current immunoprophylaxis strategies. Obstetrical policies must be assessed with respect to detection of maternal infection and liver disease, as well as with respect to perinatal transmission risk. In addition to the usual issues of drug efficacy and safety in the affected individuals, effects on the developing fetus must be considered. This paper reviews the current experience in each of these areas, and highlights the need for further investigation into this critical but often underestimated topic.
The global burden of hepatitis C
Authors: Lavanchy Daniel
Published: January 2009

Hepatitis C is of concern both to industrialized and developing countries. Preliminary unpublished estimates of the global burden of disease (GBD) attributable to HCV‐related chronic liver disease seem to be substantial. Therefore, the reduction of global mortality and morbidity related to chronic hepatitis C should be a concern to public health authorities, and primary, secondary and tertiary prevention activities should be implemented and monitored in each country, with precise targets set to be reached. In order to decide on national health policies, there is a need to estimate the burden of disease, globally, regionally and nationally. To evaluate the GBD, three components have to be assessed: 1) The global, regional and national burden of morbidity and mortality associated with HCV infection, based on prevalence, incidence, transmission and economics; 2) The natural history of HCV infection, including ‘healthy individuals’; and 3) The areas for which more research is needed. A working group was created to assist the World Health organization (WHO) in estimating the GBD associated with HCV infection.
Management and prevention of drug resistance in chronic hepatitis B
Authors: Zoulim Fabien , Durantel David , Deny Paul
Published: January 2009

The management of hepatitis B virus resistance to antivirals has evolved rapidly in recent years. The definition of resistance is now well established, with the importance of partial response and the improvement of assays to detect genotypic resistance and virological breakthrough. Data on phenotypic resistance have allowed to define the cross‐resistance profile for the main resistant mutants, providing a rationale for treatment adaptation. Clinical studies have shown that an early treatment intervention in case of a virological breakthrough or a partial response with the addition of a second drug having a complementary cross‐resistance profile allows one to maintain the majority of patients in clinical remission. The prevention of resistance should rely on the use of the most potent antivirals with a high genetic barrier to resistance as a first‐line therapy. The future perspectives are to design strategies to hasten the HBsAg clearance, which should become a new treatment endpoint, to prevent drug resistance and to decrease the incidence of complications of chronic hepatitis B.
Hepatitis B and hepatitis C in 2009
Authors: Marcellin Patrick
Published: January 2009

Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are among the most frequent viral infections in humans, and represent a major global public health problem. HBV‐ and HCV‐related chronic hepatitis are the main causes of cirrhosis and hepatocellular carcinoma (HCC) that are responsible for a high rate of morbidity and mortality. End‐stage HBV‐ and HCV‐related liver disease and HCC are the main causes of liver transplantation. In the last few years, knowledge of the epidemiology and the natural history of HBV and HCV infection has markedly improved. Furthermore, considerable progress has been made in the efficacy of therapy. New drugs and new therapeutic strategies that are currently under evaluation could further improve the efficacy of therapy in the near future.
Palaeopedological marker horizons in northern central Europe: characteristics of Lateglacial Usselo and Finow soils
Authors: KAISER KNUT , HILGERS ALEXANDRA , SCHLAAK NORBERT , JANKOWSKI MICHAŁ , KÜHN PETER , BUSSEMER SIXTEN , PRZEGIĘTKA KRZYSZTOF
Published: January 2009

Lateglacial buried soil horizons, which occur widely in sandy aeolian sequences of northern central Europe, were analysed in order to evaluate their regional pedostratigraphical and palaeoenvironmental potential. Data on stratigraphy, sedimentology, pedology, geochronology and palaeobotany from 29 palaeosol‐bearing profiles at terrestrial sites are presented. Greyish Ahb and Eb horizons occur, as well as brownish Bwb and BwAhb horizons. They are 5–30 cm thick, showing similar pedological properties except colour, and they frequently bear charcoal typically from pine. Soil classification results in Albic Arenosols (Dystric) and Brunic Arenosols (Dystric) representing palaeosols of the Usselo and Finow types, respectively. Radiocarbon dating of the palaeosols reveals a dominance of Allerød ages followed by Younger Dryas and Preboreal ages. Most luminescence ages on overlying aeolian sands date into the Allerød–Younger Dryas interval. Mapping of all Usselo and Finow soil occurrences (n=96) in northern central Europe known so far reveals a nearly closed Finow soil province between Usselo soil areas in NW Germany and central Poland, mainly situated in NE Germany. Most Usselo soils compiled contain charcoal, indicating widespread and repeated fires. Recent claims that the Usselo soil represents an event layer from rapid aeolian sedimentation caused by an extraterrestrial impact is rejected. Instead, both Usselo and Finow soils can be assumed to be pedostratigraphical marker horizons in northern central Europe and beyond.
Morphology of Younger Dryas subglacial and ice‐proximal submarine landforms, inner Vestfjorden, northern Norway
Authors: FLØISTAD KAI ROGER , LABERG JAN SVERRE , VORREN TORE O.
Published: January 2009

The sea‐floor morphology of two pronounced across‐fjord bedrock thresholds located at the mouths of Ofotfjorden and Tysfjorden, northern Norway, has been analysed based on swath bathymetry and seismic data. The Younger Dryas ice front was located here during the recession of one of the large palaeo‐ice streams of the Fennoscandian Ice Sheet. The thresholds are several kilometres long and wide, rising to several hundred metres above the adjacent sea floor, and the slopes are steep, up to 25°. The Ofotfjorden threshold is draped by acoustically discontinuous to chaotic sediments partly infilling the bedrock relief. A pattern of well‐developed, subglacial bedforms (e.g. crag‐and‐tail formations, drumlins and glacial lineations) on top of both thresholds suggests fast‐flowing ice. A series of smaller transverse ridges is identified on both thresholds and probably records ice‐front oscillations during the final deglaciation. The distal parts of the sediments have been remobilized by slides that occurred after glacial retreat from the thresholds. Earthquake activity due to the isostatic rebound following ice retreat from this area was the most likely triggering mechanism for the slides. The location of the ice front on a prominent bedrock threshold indicates that the basin configuration was important in locating the maximum position of the climatically induced re‐advance, i.e. a topographic control on the maximum Younger Dryas position in the Ofotfjorden and Tysfjorden area is suggested.
Visual fields at school‐age in children treated with vigabatrin in infancy
Authors: Gaily Eija , Jonsson Henna , Lappi Marjatta
Published: January 2009

Purpose:  The use of vigabatrin (VGB) as an antiepileptic drug (AED) has been limited by evidence showing that it causes vigabatrin‐attributed visual field loss (VAVFL) in at least 20–40% of patients exposed at school age or later. VGB is an effective drug for infantile spasms, but there are no reports on later visual field testing after such treatment. Our aim was to investigate the risk of VAVFL in school‐age children who had received VGB in infancy.

Methods:  Visual fields of 16 children treated with VGB for infantile spasms were examined by Goldmann kinetic perimetry at age 6–12 years. Normal fields were defined as the temporal meridian extending to more than 70°, and mild VAVFL between 50 and 70°. Abnormal findings were always confirmed by repeating the test. Exposure data were collected from hospital charts.

Results:  Vigabatrin was started at a mean age of 7.6 (range, 3.2–20.3) months. The mean duration of therapy was 21.0 (9.3–29.8) months and cumulative dose 655 g (209–1,109 g). Eight children were never treated with other AEDs, five received only adrenocorticotropic hormone (ACTH) in addition to VGB, and three children had been treated with other AEDs. Fifteen children had normal visual fields. Mild VAVFL was observed in one child (6%) who had been treated with VGB for 19 months and who received a cumulative dose of 572 g.

Conclusions:  The risk of VAVFL may be lower in children who are treated with VGB in infancy compared to patients who receive VGB at a later age.
Glutamine induces epileptiform discharges in superficial layers of the medial entorhinal cortex from pilocarpine‐treated chronic epileptic rats in vitro
Authors: Sandow Nora , Zahn Robert K. , Gabriel Siegrun , Heinemann Uwe , Lehmann Thomas‐Nicolas
Published: January 2009

Purpose:  Glutamine (GLN) is a precursor for synthesis of glutamate and γ‐aminobutyric acid (GABA) and has been found in the cerebrospinal fluid (CSF) at mean concentrations of 0.6 mM. Experiments on slices are usually performed in artificial CSF (aCSF) kept free of amino acids. Therefore, the role of glutamine, particularly in tissue of epileptic animals, remains elusive.

Methods:  Using extracellular recordings we studied effects of GLN on field potentials and stimulus‐evoked field responses in the medial entorhinal cortex (MEC) of combined entorhinal cortex hippocampal slices from pilocarpine‐treated chronic epileptic rats and age‐matched saline‐injected control rats.

Results:  In presence of GLN (0.5 and 2 mM) recurrent epileptiform discharges (REDs) were observed in slices from epileptic rats (64% and 80%, respectively), but not in slices from control rats. REDs were restricted to the superficial MEC, suppressed by the α‐Amino‐3‐hydroxy‐5‐methyl‐4‐isoxazol‐propionate (AMPA)/kainate receptor antagonist 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (30 μM), attenuated by the inhibitor of neuronal glutamine transporters methylamino‐isobutyric acid (10 mM), and apparently augmented and prolonged by the GABAA receptor antagonist bicuculline‐methiodide (5 μM). In contrast, amplitudes of stimulus evoked nonsynaptic and synaptic field responses increased in slices from control rats (+23% and +12% of the reference values) and insignificantly less or not in those of epileptic rats (+6.5% and −0.25%, respectively). Notably, stimulus‐evoked slow negative transients confined to slices of epileptic animals were reduced in amplitude (−18%).

Discussion:  In combined entorhinal hippocampal slices from chronic epileptic animals, GLN induces glutamatergic REDs via neuronal uptake in superficial layers of the MEC where inhibitory function seemed to be partially preserved.
Oral automatisms induced by stimulation of the mesial frontal cortex
Authors: Unnwongse Kanjana , Lachhwani Deepak , Tang‐Wai Richard , Matley Kirk , O’Connor Timothy , Nair Dileep , Bingaman William , Wyllie Elaine , Diehl Beate
Published: January 2009

Extraoperative electrical stimulation is frequently used to identify eloquent areas in patients with pharmacoresistant epilepsy who undergo subdural grid evaluation for epilepsy surgery. Oral automatisms elicited by cortical stimulation have been described in the mesial temporal lobe, but also in the mesial frontal lobe, particularly the cingulate gyrus. However oral automatisms attributed to stimulation in the superior frontal gyrus without afterdischarges have never been reported. Herein we present two patients with right frontal lobe epilepsy with oral automatisms induced by electrical stimulation of the right mesial superior frontal gyrus.
A substantial number of Rasmussen syndrome patients have increased IgG, CD4+ T cells, TNFα, and Granzyme B in CSF
Authors: Takahashi Yukitoshi , Mine Jyun , Kubota Yuko , Yamazaki Etsuko , Fujiwara Tateki
Published: January 2009

Purpose:  We studied the immunologic molecules in cerebrospinal fluid (CSF) and discussed their evolutional changes in pediatric patients with Rasmussen syndrome (RS).

Methods:  CSF samples collected from 27 patients with RS (average onset age, 7.5 ± 5.6 years) were studied. Cell count, protein, glucose, albumin, chloride, and immunoglobulin G (IgG) levels were measured by conventional methods. Surface markers of lymphocytes in CSF were examined by a cell sorter. Granzyme B, interferon γ (IFNγ), interleukin 4 (IL‐4), tumor necrosis factor α (TNFα), and IL‐12 in CSF were quantitated by enzyme‐linked immunosorbent assay (ELISA). Autoantibodies against GluR ε2 (NR2B) were examined by immunoblot.

Results:  The data of the first CSF examination showed that IgG levels (Mann‐Whitney U test, p < 0.01), CD4+ T cells (p = 0.02), TNFα levels (p < 0.01), and Granzyme B levels (p < 0.01) were elevated compared with disease controls. White blood cell count, IFNγ level, IL‐12 level, and Granzyme B level were elevated, especially in the early stage of disease. CD4+ T cells, CD8+ cells, CD3+ T cells, IgG levels, and TNFα levels were elevated at all stages of disease evolution. Protein levels and albumin levels were elevated in the progressed stage. Autoantibodies against GluR ε2 (NR2B) (IgG) were found in 50% of patients in the early stage, and the positive rate was low at the progressed stage.

Discussion:  The present findings suggest that complex pathophysiologic mechanisms involving CD4+ T cells and CD8+ T cells change evolutionally during the progression of RS. A crucial cytotoxic process occurs in the early stage, and declines in the progressed stage.
Facial emotion recognition impairment in chronic temporal lobe epilepsy
Authors: Meletti Stefano , Benuzzi Francesca , Cantalupo Gaetano , Rubboli Guido , Tassinari Carlo Alberto , Nichelli Paolo
Published: January 2009

Purpose:  To evaluate facial emotion recognition (FER) in a cohort of 176 patients with chronic temporal lobe epilepsy (TLE).

Methods:  FER was tested by matching facial expressions with the verbal labels for the following basic emotions: happiness, sadness, fear, disgust, and anger. Emotion recognition performances were analyzed in medial (n = 140) and lateral (n = 36) TLE groups. Fifty healthy subjects served as controls. The clinical and neuroradiologic variables potentially affecting the ability to recognize facial expressions were taken into account.

Results:  The medial TLE (MTLE) group showed impaired FER (86% correct recognition) compared to both the lateral TLE patients (FER = 93.5%) and the controls (FER = 96.4%), with 42% of MTLE patients recording rates of FER that were lower [by at least 2 standard deviations (SDs)] than the control mean. The MTLE group was impaired compared to the healthy controls in the recognition of all basic facial expressions except happiness. The patients with bilateral MTLE were the most severely impaired, followed by the right and then the left MTLE patients. FER was not affected by type of lesion, number of antiepileptic drugs (AEDs), aura semiology, or gender. Conversely, the early onset of seizures/epilepsy was related to FER deficits. These deficits were already established in young adulthood, with no evidence of progression in older MTLE patients.

Conclusion:  These results on a large cohort of TLE patients demonstrate that emotion recognition deficits are common in MTLE patients and widespread across negative emotions. We confirm that early onset seizures with right or bilateral medial temporal dysfunction lead to severe deficits in recognizing facial expressions of emotions.
Focal cortical dysplasia: A genotype–phenotype analysis of polymorphisms and mutations in the TSC genes
Authors: Gumbinger Christoph , Rohsbach Constantin B. , Schulze‐Bonhage Andreas , Korinthenberg Rudolf , Zentner Josef , Häffner Monika , Fauser Susanne
Published: January 2009

Purpose:  Focal cortical dysplasia (FCD) is a common cause of pharmacoresistant human epilepsy. FCD has frequently been discussed as a “forme fruste” of tuberous sclerosis complex (TSC) because of the radiologic and histologic resemblance of dysplastic areas to tubers in TSC. Mutations or a germ‐line predisposition in terms of increased polymorphisms in the TSC genes have been presumed to influence the pathogenesis of FCD. A detailed genotype–phenotype analysis of these patients has not been performed so far.

Methods:  In this study, 33 patients with FCD (among them 23 with FCD type 2 and 4 patients with multifocal FCD) were investigated (1) clinically as to dermatologic manifestations, retinal hamartoma, cardial rhabdomyoma, and renal angiomyolipoma, and (2) genetically by considering lesional brain tissue and blood using single strand conformation polymorphism (SSCP) electrophoresis and sequencing of the TSC1 and TSC2 genes.

Results:  In the clinical examinations, no subtle features of TSC could be detected in this large group of patients with FCD, pointing to the fact that this is a different patient group without clinical overlap. Several sequence alterations were found in the TSC1 and TSC2 genes in both lesional brain tissue and blood of FCD patients, however, in similar frequencies to that of the normal population. Moreover, most of these sequence alterations were silent.

Discussion:  This study shows that FCD—even multifocal FCD—is not caused by mutations in the TSC genes and seems not to be promoted by polymorphisms in the TSC genes. Therefore, FCD cannot be regarded as a “forme fruste” of TSC.
Palilalia, echolalia, and echopraxia–palipraxia as ictal manifestations in a patient with left frontal lobe epilepsy
Authors: Cho Yang‐Je , Han Sang‐Don , Song Sook Keun , Lee Byung In , Heo Kyoung
Published: January 2009

Palilalia is a relatively rare pathologic speech behavior and has been reported in various neurologic and psychiatric disorders. We encountered a case of palilalia, echolalia, and echopraxia–palipraxia as ictal phenomena of left frontal lobe epilepsy. A 55‐year‐old, right‐handed man was admitted because of frequent episodes of rapid reiteration of syllables. Video‐electroencephalography monitoring revealed stereotypical episodes of palilalia accompanied by rhythmic head nodding and right‐arm posturing with ictal discharges over the left frontocentral area. He also displayed echolalia or echopraxia–palipraxia, partially responding to an examiner’s stimulus. Magnetic resonance imaging revealed encephalomalacia on the left superior frontal gyrus and ictal single photon emission computed tomography showed hyperperfusion just above the lesion, corresponding to the left supplementary motor area (SMA), and subcortical nuclei. This result suggests that the neuroanatomic substrate involved in the generation of these behaviors as ictal phenomena might exist in the SMA of the left frontal lobe.
Sleep‐related hypermotor seizures in aspartylglucosaminuria: A case report
Authors: Ambrosetto Giovanni , Santucci Margherita
Published: January 2009

From the age of 24 years a young man with a definitive diagnosis of aspartylglucosaminuria (AGU) presented short‐lasting sleep‐related paroxysmal events characterized by sudden awakening with a frightened look, hyperventilation, and complex bilateral motor activity. Nocturnal video‐polysomnography recorded several events consistent with a diagnosis of hypermotor epileptic seizures. This pattern of sleep‐related epileptic seizures has been reported in rare familial cases, more often in cryptogenic and symptomatic patients in the spectrum of nocturnal frontal lobe epilepsy. Epilepsy and sleep‐related nonepileptic problems are common in patients with AGU, but no case of hyperkinetic nocturnal frontal lobe seizures has been reported to date. Differential diagnosis of abnormal paroxysmal motor events in sleep is frequently a challenge for the clinician: Video‐polysomnographic recordings might serve to identify the possible epileptic origin of some of the excessive motor activities during sleep referred in patients with AGU.
Epilepsy surgery in the first 3 years of life: A Canadian survey
Authors: Steinbok Paul , Gan Peter Y.C. , Connolly Mary B. , Carmant Lionel , Barry Sinclair D. , Rutka James , Griebel Robert , Aronyk Keith , Hader Walter , Ventureyra Enrique , Atkinson Jeffrey
Published: January 2009

Objective:  To determine the clinical characteristics, surgical challenges, and outcome in children younger than 3 years of age undergoing epilepsy surgery in Canada.

Methods:  Retrospective data on patients younger than age 3 years who underwent epilepsy surgery at multiple centers across Canada from January 1987 to September 2005 were collected and analyzed.

Results:  There were 116 patients from eight centers. Seizure onset was in the first year of life in 82%, and mean age at first surgery was 15.8 months (1–35 months). Second surgeries were done in 27 patients, and a third surgery in 6. Etiologies were malformations of cortical development (57), tumor (22), Sturge‐Weber syndrome (19), infarct (8), and other (10). Surgeries comprised 40 hemispheric operations, 33 cortical resections, 35 lesionectomies, 7 temporal lobectomies, and one callosotomy. There was one surgical mortality. The most common surgical complications (151 operations in 116 patients) were infection (17) and aseptic meningitis in 13. Of 107 patients with seizure outcome assessed more than one year postoperatively, 72 (67.3%) were seizure free (Engel I), 15(14%) had >90% improvement (Engel II), 12 had >50% improvement (Engel III), and 8 did not benefit from surgery (Engel IV). Development improved in 55.3% after surgery.

Conclusion:  Epilepsy surgery in children younger than 3 years of age is relatively safe and is effective in controlling seizures. Very young age is not a contraindication to surgery in children with refractory epilepsy, and early surgery may impact development positively.
The spectrum of benign myoclonus of early infancy: Clinical and neurophysiologic features in 102 patients
Authors: Caraballo Roberto H. , Capovilla Giuseppe , Vigevano Federico , Beccaria Francesca , Specchio Nicola , Fejerman Natalio
Published: January 2009

Purpose: To redefine benign myoclonus of early infancy (BMEI) through analysis of clinical and neurophysiologic features in 102 patients with the aim to widen the spectrum of the syndrome, including a number of different clinical expressions of transient nonepileptic paroxysmal movements occurring in normal infants.

Methods: We recruited patients from one center in Argentina and two in Italy, including infants with normal neurologic and psychomotor development presenting with brief paroxysmal abnormal movements. Children with motor phenomena occurring only during sleep were excluded. Patients with abnormal interictal or ictal electroencephalography (EEG) findings were also excluded. The follow‐up ranged from 2–40 years.

Results: One hundred and two infants (60 male) met the inclusion criteria. Age at onset ranged from 1–12 months, with a median age of 6.2 months. The following nonepileptic paroxysmal motor phenomena were recognized: (1) myoclonus, (2) spasms and brief tonic contractions, (3) shuddering, (4) atonia or negative myoclonus, (5) more than one type of motor phenomenon. In the majority of cases the episodes occurred only while awake and repeated several times a day. In 45 (44.1%) of the 102 cases contractions appeared in clusters.

Conclusions: Based on the analysis of clinical and EMG features in this large series of infants, we postulate that the spectrum of the syndrome is wider than initially suspected, and that the different transient motor manifestations and their correlation with different EMG patterns will allow recognition of this definitely benign condition comprising a variety of episodic motor phenomena in normal babies.
Assessment and surgical outcomes for mild type I and severe type II cortical dysplasia: A critical review and the UCLA experience
Authors: Lerner Jason T. , Salamon Noriko , Hauptman Jason S. , Velasco Tonicarlo R. , Hemb Marta , Wu Joyce Y. , Sankar Raman , Donald Shields W. , Engel Jr Jerome , Fried Itzhak , Cepeda Carlos , Andre Veronique M. , Levine Michael S. , Miyata Hajime , Yong William H. , Vinters Harry V. , Mathern Gary W.
Published: January 2009

Recent findings on the clinical, electroencephalography (EEG), neuroimaging, and surgical outcomes are reviewed comparing patients with Palmini type I (mild) and type II (severe) cortical dysplasia. Resources include peer‐reviewed studies on surgically treated patients and a subanalysis of the 2004 International League Against Epilepsy (ILAE) Survey of Pediatric Epilepsy Surgery. These sources were supplemented with data from University of California, Los Angeles (UCLA). Cortical dysplasia is the most frequent histopathologic substrate in children, and the second most common etiology in adult epilepsy surgery patients. Cortical dysplasia patients present with seizures at an earlier age than other surgically treated etiologies, and 33–50% have nonlocalized scalp EEG and normal magnetic resonance imaging (MRI) scans. 2‐(18F)Fluoro‐2‐deoxy‐D‐glucose positron emission tomography (FDG‐PET) is positive in 75–90% of cases. After complete resection, 80% of patients are seizure free compared with 20% with incomplete resections. Compared with type I, patients with type II cortical dysplasia present at younger ages, have higher seizure frequencies, and are extratemporal. Type I dysplasia is found more often in adult patients in the temporal lobe and is often MRI negative. These findings identify characteristics of patients with mild and severe cortical dysplasia that define surgically treated epilepsy syndromes. The authors discuss future challenges to identifying and treating medically refractory epilepsy patients with cortical dysplasia.
Altered Impulse Control in Alcohol Dependence: Neural Measures of Stop Signal Performance
Authors: Li Chiang‐shan Ray , Luo Xi , Yan Peisi , Bergquist Keri , Sinha Rajita
Published: January 2009

Background:  Altered impulse control has been implicated in the shaping of habitual alcohol use and eventual alcohol dependence. We sought to identify the neural correlates of altered impulse control in 24 abstinent patients with alcohol dependence (PAD), as compared to 24 demographics matched healthy control subjects (HC). In particular, we examined the processes of risk taking and cognitive control as the neural endophenotypes of alcohol dependence.

Methods:  To this end, functional magnetic resonance imaging (fMRI) was conducted during a stop signal task (SST), in which a procedure was used to elicit errors in the participants. The paradigm allowed trial‐by‐trial evaluation of response inhibition, error processing, and post‐error behavioral adjustment. Furthermore, by imposing on the subjects to be both fast and accurate, the SST also introduced a distinct element of risk, which participants may or may not avert during the task. Brain imaging data were analyzed with Statistical Parametric Mapping in covariance analyses accounting for group disparity in general performance.

Results:  The results showed that, compared to HC, PAD demonstrated longer go trial reaction time (RT) and higher stop success rate (SS%). HC and PAD were indistinguishable in stop signal reaction time (SSRT) and post‐error slowing (PES). In a covariance analysis accounting for go trial RT and SS%, HC showed greater activity in the left dorsolateral prefrontal cortex than PAD, when subjects with short and long SSRT were contrasted. By comparing PAD and HC directly during stop errors (SE), as contrasted with SS, we observed greater activity in PAD in bilateral visual and frontal cortices. Compared to HC, PAD showed less activation of the right dorsolateral prefrontal cortex during PES, an index of post‐error behavioral adjustment. Furthermore, PAD who showed higher alcohol urge at the time of the fMRI were particularly impaired in dorsolateral prefrontal activation, as compared to those with lower alcohol urge. Finally, compared to HC subjects, PAD showed less activity in cortical and subcortical structures including putamen, insula, and amygdala during risk‐taking decisions in the SST.

Conclusion:  These preliminary results provided evidence for altered neural processing during impulse control in PAD. These findings may provide a useful neural signature in the evaluation of treatment outcomes and development of novel pharmacotherapy for alcohol dependence.
Healthcare Costs Associated with Depression in Medically Ill Fee‐for‐Service Medicare Participants
Authors: Unützer Jürgen , Schoenbaum Michael , Katon Wayne J. , Fan Ming‐Yu , Pincus Harold A. , Hogan Diane , Taylor Jennifer
Published: January 2009

OBJECTIVES: To examine the association between depression and healthcare costs in medically ill fee‐for‐service (FFS) Medicare recipients.

STUDY DESIGN: Observational analysis of Medicare claims data.

SETTING: Medicare Health Support (MHS) program at Green Ribbon Health.

PARTICIPANTS: Fourteen thousand nine hundred two participants with diabetes mellitus, congestive heart failure (CHF), or both.

MEASUREMENTS: This study examined participant data for a 12‐month period before MHS enrollment (collected between November 2004 and August 2006). Twelve‐month healthcare costs (based on Medicare claims) in 2,108 participants with International Classification of Diseases, Ninth Revision, claims diagnoses of depression, 1,081 participants with possible depression (positive depression screen on the two‐item Patient Health Questionnaire or self reported antidepressant use), and 11,713 participants without depression were compared. Gamma regression models were used to adjust for demographic and clinical differences and nonnormal distribution of cost data.

RESULTS: Participants with depression had significantly higher total healthcare costs than those without ($20,046 vs $11,956; P<.01). Higher costs were observed in participants with depression in every cost category except specialty mental health care, which accounted for less than 1% of total healthcare costs. Participants with depression had higher costs in each quartile of increasing medical severity (measured using the Charlson Comorbidity Index). These differences remained statistically significant after adjusting for demographic and other clinical differences.

CONCLUSION: Depression is associated with significantly higher healthcare costs in FFS Medicare recipients with diabetes mellitus and CHF. Only a small proportion of the increased costs are spent on mental health specialty care.
Activity of clotting factors in fresh‐frozen plasma during storage at 4°C over 6 days
Authors: Von Heymann Christian , Keller Mareike Kristina , Spies Claudia , Schuster Michael , Meinck Kristian , Sander Michael , Wernecke Klaus‐Dieter , Kiesewetter Holger , Pruss Axel
Published: January 2009

BACKGROUND: Fresh‐frozen plasma (FFP) requires thawing, which delays availability. We investigated clotting factor activity and bacterial contamination of FFP when stored at 4°C ± 2°C for 6 days.

STUDY DESIGN AND METHODS: Plasma of 20 healthy plasma donors was sampled, frozen, and analyzed at baseline and repeatedly over a period of 6 days after thawing. The activity of fibrinogen, Factor (F)II, FV, FVII, FVIII, F IX, FX, XI, FXII, FXIII, antithrombin III (ATIII), von Willebrand factor antigen (VWF‐Ag), protein C (PC), and free protein S (FPS) were determined and analyzed over time.

RESULTS: Immediately after thawing there was a significant decrease of fibrinogen (−9%), FII (−7%), FV (−14%), FVII (−12%), FX (−11%), FXIII (−20%), PC (−7%), and ATIII (−4%), whereas FVIII (+8%), F IX (+1%), FXI (+11%), FXII (−1%), FPS (−1%), and VWF‐Ag (−6%) remained stable without significant change. Over 6 days after thawing fibrinogen, ATIII (+2%) and VWF‐Ag (+2%) remained stable whereas FXII (+2%), FXIII (+6%), and PC (+3%) changed significantly over time and increased at the end. FII (−8%), FV (−16%), FVII (−31%), FVIII (−47%), F IX (−12%), FX (−10%), FXI (−25%), and FPS (±0%) changed also significantly over time and decreased at the end. All clotting factors and inhibitors remained within the reference range requested by quality assurance regulations. No FFP bag showed bacterial contamination.

CONCLUSION: This provides evidence for maintaining quality of thawed FFP and may improve rapid availability in emergency situations and reduce cost for health care givers.
P‐selectin mRNA is maintained in platelet concentrates stored at 4°C
Authors: Stiegler Gabriele , Fischer Gottfried , Ramanathan Gajalakshmi , Bencur Peter , Weigel Günter , Mannhalter Christine
Published: January 2009

BACKGROUND: Platelets (PLTs) contain mRNA and synthesize proteins in response to activation. Most guidelines for PLT concentrates (PCs) recommend ambient temperature for storage but the impact of the storage temperature on PLT mRNA content has not yet been investigated.

STUDY DESIGN AND METHODS: Ten leukoreduced apheresis PCs were split and stored at 22 and 4°C. P‐selectin mRNA, its expression on PLTs, and its soluble form were quantified. In parallel, cellular (cell count, mean PLT volume), metabolic (pH, pO2, pCO2, HCO3, glucose), and functional markers (swirling, hypotonic shock response, aggregation to collagen) were analyzed. Rotation thrombelastography was used to monitor the hemostatic potential of PLTs. All measurements were performed on Days 1 and 5 of storage.

RESULTS: After 5 days of storage at 4°C, only 31 ± 27 percent of P‐selectin mRNA and 29 ± 41 percent of glyceraldehyde‐3‐phosphate dehydrogenase mRNA were lost, while minute amounts of the mRNAs were detectable at 22°C. In PCs stored at 4°C the percentage of P‐selectin–positive PLTs was significantly higher when compared to PCs stored at 22°C. Soluble P‐selectin concentrations did not significantly differ between both storage temperatures. Thrombelastography revealed significantly shorter reaction times in PLTs kept at 4°C.

CONCLUSION: Our data indicate that storage at 4°C is accompanied by maintained mRNA levels. PLTs with intact mRNA levels and short reaction times in thrombelastography might be functionally superior to PLTs that are devoid of mRNA and show less augmented P‐selectin surface expression. In therapeutic applications, that is, if PLTs are transfused to control acute bleeding, PLTs kept at 4°C may be advantageous.
Assessment of safety in neonates for transfusion of platelets and plasma prepared with amotosalen photochemical pathogen inactivation treatment by a 1‐month intravenous toxicity study in neonatal rats
Authors: Ciaravino Vic , Hanover Jessica , Lin Lily , Sullivan Theresa , Corash Laurence
Published: January 2009

BACKGROUND: It is estimated that approximately 300,000 neonates undergo transfusions annually. The neonatal immune system is immature, making such patients more susceptible to the effects associated with transfusion‐transmitted bacteria, viruses, protozoa, and white blood cells (WBCs). The INTERCEPT Blood System is a photochemical process (PCT) utilizing amotosalen and long‐wavelength ultraviolet to inactivate pathogens and WBCs in both platelet (PLT) and plasma components for transfusion. A series of clinical studies has shown PCT PLTs and PCT plasma to be safe and effective for transfusion in adults and pediatric patients. Because clinical studies in neonates are technically difficult and ethically challenging, preclinical toxicologic studies were conducted in neonatal rats to evaluate the safety of PCT blood components for neonates.

STUDY DESIGN AND METHODS: This study examined daily intravenous administration to neonatal rats of amotosalen in 35 percent:65 percent plasma:InterSol from 1 µg per kg per day (representing 1‐unit transfusion) to 457 µg per kg per day (representing multiple transfusions) from Postnatal Day 4 (PND4) to PND31. Rats were observed for viability, clinical signs, and body weights until PND31 and then subjected to pathology evaluation. Hematology, clinical chemistry, and urinalysis data were also collected on PND31. Toxicokinetic parameters were evaluated on PND4 and PND31.

RESULTS: There were no amotosalen‐related effects on clinical signs, body weight, hematology, clinical chemistry, urinalysis, gross pathology, or histopathology, despite the exposure of neonatal rats to amotosalen concentrations as high as approximately 48 times the standard exposure in adult patients.

CONCLUSION: This study demonstrates the safety of PCT for transfusion in neonatal rats and augments data from other studies and clinical use supporting the use of PCT in neonatal patients.
High‐resolution HLA matching in double‐umbilical‐cord‐blood reduced‐intensity transplantation in adults
Authors: Delaney Meghan , Cutler Corey S. , Haspel Richard L. , Yeap Beow Y. , McAfee Steven L. , Dey Bimalangshu R. , Attar Eyal , Kao Grace , Alyea Edwin P. , Koreth John , Ho Vincent T. , Saidman Susan , Liney Deborah , Sese Doreen , Soiffer Robert J. , Spitzer Thomas R. , Antin Joseph H. , Ballen Karen K.
Published: January 2009

BACKGROUND: Double‐cord‐blood transplantation (DCBT) offers an option for patients receiving reduced‐intensity transplants. These unique transplants have two donors, both of whom are usually HLA mismatched at one to two loci.

STUDY DESIGN AND METHODS: Fifty‐three patients were recipients of a reduced‐intensity DCBT. Cords were at least 4/6 allele‐level HLA‐A, ‐B, and ‐DR match with the patient and each other with a minimum combined cell dose of more than 3.7 × 107 total nucleated cells per kg. Twenty‐one patients received cyclosporine/mycophenolate mofetil and 32 patients received sirolimus/tacrolimus (SIR/TAC) for graft‐versus‐host disease prophylaxis. The effect of allele level HLA typing on clinical endpoints of overall survival (OS), disease‐free survival (DFS), engraftment, and acute graft‐versus‐host disease (aGVHD) were assessed.

RESULTS: Neutrophil (p = 0.001) engraftment and platelet engraftment (p = 0.027) were significantly faster in patients who have closer Class I (HLA‐A, ‐B, ‐C) matching. Neutrophil engraftment was faster in patients who had closer HLA‐B matching to their combined cords (p = 0.007). There was a low incidence of aGVHD overall, especially in the SIR/TAC group. Class I HLA matching had no effect on aGVHD. HLA‐DR and ‐DQ had no effect on engraftment or aGVHD.

CONCLUSION: Class I allele matching, and HLA‐B matching specifically, were associated with faster neutrophil engraftment. High‐resolution HLA matching did not affect OS or DFS.
Racing to Theory or Retheorizing Race? Understanding the Struggle to Build a Multiracial Identity Theory
Authors: Rockquemore Kerry Ann , Brunsma David L. , Delgado Daniel J.
Published: January 2009

Empirical research on the growing multiracial population in the United States has focused largely on the documentation of racial identification, analysis of psychological adjustment, and understanding the broader political consequences of mixed‐race identification. Efforts toward theory construction on multiracial identity development, however, have been largely disconnected from empirical data, mired in disciplinary debates, and bound by historically specific assumptions about race and racial group membership. This study provides a critical overview of multiracial identity development theories, examines the links between theory and research, explores the challenges to multiracial identity theory construction, and proposes considerations for future directions in theorizing racial identity development among the mixed‐race population.
Multiracial Faces: How Categorization Affects Memory at the Boundaries of Race
Authors: Pauker Kristin , Ambady Nalini
Published: January 2009

Monoracial and multiracial individuals are likely to have different conceptualizations of race and subsequently different approaches toward racial ambiguity. In particular, monoracial individuals may be more likely to rely on categories when processing ambiguous faces, whereas multiracial individuals may tend to ignore such categorizations due to a reduced tendency to essentialize race. We compared monoracial (White and Asian) and biracial (Asian/White) individuals' memory patterns. Specifically, we examined participants' memory for White, Asian, and biracial faces labelled as either White or Asian. Both White and Asian participants relied on the labels, remembering faces labeled as the in‐group better than faces labeled as the out‐group. Biracial participants relied less on the labels, exhibiting better recognition memory overall. Biracial participants’ memory performance was also highly correlated with a less essentialist view of human traits. This cognitive flexibility may serve an adaptive function for biracial individuals and contribute to enhanced facial recognition.
Policing the Borderlands: White‐ and Black‐American Newspaper Perceptions of Multiracial Heritage and the Idea of Race, 1996–2006
Authors: Thornton Michael C.
Published: January 2009

By employing a new policy of “check all that apply,” the Census Bureau accommodated a mushrooming multiracial lobby demanding that its members be allowed a right to self‐identification. With its implied shifting meaning of race, newspapers portrayed the reaction to this change as a firestorm of debate along racial fault lines, highlighted by Black‐American inferences that this was a perilous decision. Using textual analysis, I examine from 1996 to 2006 how five Black‐American and three White‐American newspapers characterized multiracial people. White‐American papers framed the discussion in two ways: (a) multiracial people epitomize a new era in which race has lost its bite, and (b) Black America stands in the way of their gaining their civil rights. There were also two frames for the Black‐American papers: (a) The lobby advocates individual identity and is undergirded by denial or distancing from Blackness, and (b) that focus undermines Black America's future by playing into the misguided notion that race is socially insignificant.
My Choice, Your Categories: The Denial of Multiracial Identities
Authors: Townsend Sarah S. M. , Markus Hazel R. , Bergsieker Hilary B.
Published: January 2009

Mixed‐race individuals often encounter situations in which their identities are a source of tension, particularly when expressions of multiracial and biracial identity are not supported or allowed. Two studies examined the consequences of this identity denial. In Study 1, mixed‐race participants reported that their biracial or multiracial identity caused tension in a variety of contexts. Study 2 focused on one often‐mentioned situation: completing a demographic questionnaire in which only one racial background can be specified. Relative to mixed‐race participants who were permitted to choose multiple races, those compelled to choose only one showed lower subsequent motivation and self‐esteem. These studies demonstrate the negative consequences of constraining mixed‐race individuals’ expression of their chosen racial identity. Policy implications for the collection of racial and ethnic demographic data are discussed.