bluuebunny/crossref_metadata_2025 huggingface dataset:
Normative Trends in Children's Perceptions of Availability and Utilization of Attachment Figures in Middle Childhood
Authors: Kerns Kathryn A. , Tomich Patricia L. , Kim Patricia
Published: January 2006

Two studies addressed the normative aspects of attachments to mothers and fathers in middle childhood. Using both cross‐sectional and longitudinal comparisons, we tested the hypothesis that children show no changes in perceptions of availability of attachment figures across the later middle childhood years, but do utilize attachment figures less at older ages. The first study included a cross‐sectional comparison of third and sixth graders, and the second study was a follow‐up on the third graders when they were in fifth grade. Both studies suggested a decline in utilization, but not in perceptions of availability of attachment figures within the later middle childhood years. Study 1 also demonstrated that children turn to parents to meet attachment needs, and peers to meet companionship needs. Study 2 examined individual differences in attachment by exploring how changes in attachment to mothers from third to fifth grade were related to children's social adjustment at fifth grade. Increases in perceptions of availability forecast better emotional and behavioral regulation at fifth grade. Changes in utilization of attachment figures showed both linear and nonlinear relations to regulation.
Preschool Boys with Pervasive Hyperactivity: Early Peer Functioning and Mother–Child Relationship Influences
Authors: Keown Louise J. , Woodward Lianne J.
Published: January 2006

This study compared the peer functioning of a community sample of preschool boys with pervasive hyperactivity (N=33) and comparison boys (N=34), and examined the extent to which any differences in peer functioning between these groups could be explained by comorbid child conduct problems and parenting factors. The quality of boys’ peer relations was assessed on the basis of teacher and observer ratings of peer‐related behavior at preschool. The quality of parenting and boys’ behavior at home were assessed using the Parental Account of Children's Symptoms Interview, the Parenting Scale, and videotaped mother–son interactions. Boys with hyperactive behavior problems showed higher rates of aggressive, noncompliant, and nonsocial behaviors, and lower rates of prosocial behavior and peer acceptance than boys in the comparison group. These between‐group differences in social functioning remained significant following statistical control for the effects of conduct problems, highlighting the wide range of peer difficulties associated with preschool hyperactivity. Results of further analyses suggest that the quality of early mother–child interactions and the behavioral features of hyperactivity may make unique contributions to the 00development of peer relationship difficulties in preschool children with pervasive hyperactivity.
Self‐perceived Social Acceptance and Peer Social Standing in Children with Aggressive–Disruptive Behaviors
Authors: Pardini Dustin A. , Barry Tammy D. , Barth Joan M. , Lochman John E. , Wells Karen C.
Published: January 2006

Examining children's perceptions of their social acceptance in conjunction with others’ ratings of their peer social standing can enhance our understanding of the heterogeneity in children exhibiting disruptive behavior problems. Using a sample of 213 youth rated in the top 31 percent of their class on aggressive–disruptive behaviors, the current study examined the interaction between children's perceptions of their social acceptance and their peer‐rated social standing in predicting emotional and behavioral problems. Overall, lower peer‐rated social standing was associated with higher levels of antisocial behavior, academic problems, and hyperactivity/inattention. On the other hand, higher self‐perceived social acceptance was associated with increased levels of peer‐rated fighting at school. For children who were rated as having high social standing among their peers, poorer self‐perceived social acceptance was associated with increased oppositional behaviors and conduct problems at home. In addition, children who reported lower self‐perceived social acceptance exhibited increased levels of depressive symptoms, even when they were relatively well liked by their peers. The potential implications for working with subgroups of children with aggressive–disruptive behaviors are discussed.
Children's and Adolescents’ Expectations of Aggressive Responses to Provocation: Females Predict More Hostile Reactions in Compatible Dyadic Relationships
Authors: Benenson Joyce F. , Sinclair Nancy , Dolenszky Eva
Published: January 2006

Children and adolescents between 6 and 15 years of age were asked to report on typical same‐sex peers’ aggressive responses to a hostile act that had occurred in dyads and groups that were either compatible or incompatible. Results demonstrated that females were expected to display the highest levels of aggression in compatible one‐on‐one relationships as opposed to in compatible group relationships or in incompatible relationships. Males did not differ across the type of relationship in the level of aggression that they were expected to display. The connection between investment in a relationship and aggression is considered.
Gender Differences in Verbal Communication between Popular and Unpopular Children During an Interactive Task
Authors: Murphy Suzanne M. , Faulkner Dorothy
Published: January 2006

This study investigated gender differences in communication effectiveness between popular and unpopular 5‐ to 7‐year‐old children. Because previous research suggests that there may be gender differences in how popular and unpopular children communicate with each other, 24 same‐gender pairs (each containing a popular and an unpopular child) were videotaped playing a game. Communication effectiveness was assessed by measuring the incidence of forms of speech associated with successful collaboration (questions, directives, and elaborations). Results revealed a popularity by gender interaction. Popular girls used a greater incidence of these forms of speech compared to unpopular girls. By contrast, there was no difference in the speech of popular and unpopular boys. Findings are interpreted in relation to the nature of the task and the characteristics of popular and unpopular children.
Concepts of Real and Imaginary Friendships in Early Childhood
Authors: Gleason Tracy R. , Hohmann Lisa M.
Published: January 2006

This investigation focused on the friendship concepts of pre‐school‐aged children. Eighty‐four 3‐ to 5‐year‐old children responded to questions about social provisions, or benefits of relationships, available from reciprocal friends (both children in a pair nominate each other as friends), unilateral friends (one child nominates the other), non‐friends (neither child of a pair nominates the other), and imaginary friends (for those who had them). Results indicated that reciprocal and imaginary friends were the best sources of social provisions, followed by unilateral friends and non‐friends. Major implications are that children draw distinctions between reciprocal and unilateral friends based on the levels of social provisions available in these relationships, and that relationship schemas underlying relationships with imaginary companions may be akin to those for reciprocal friends. Children's friendship schemata may also differ by gender, as girls discriminated more than boys between reciprocal and unilateral friends for the social provision of companionship.
Triadic Interaction among Newly Acquainted 2‐year‐olds
Authors: Ishikawa Fumiko , Hay Dale F.
Published: January 2006

Are children as young as 2 years old able to interact in groups of three? The study applied the family triad model first introduced by Parke, Power, and Gottman (1979) to the case of peer interaction. In Experiment 1, the model was refined for use in studies of peer interaction and applied to an existing dataset of 16 triads of newly acquainted 24‐month‐olds. In Experiment 2, the triadic coding system was further refined and applied to 12 single‐sex triads of newly acquainted 2‐year‐olds. The findings demonstrated that 2‐year‐olds are capable of triadic interaction although the predominant interaction pattern in triads is still dyadic. Contrary to past reports, triadic interaction was more likely to occur when the children were not in conflict. Both girls and boys were capable of triadic interaction.
An Exploration of Students’ Statistical Thinking
Authors: Groth Randall E.
Published: January 2006

The statistical thinking exhibited by 14–19 year‐old students during clinical interview sessions is described. The students’ thinking with regard to fundamental statistics concepts is reported in order to help inform instructional practice.
Accuracy and Precision in Measurements: Two Complementary Approaches
Authors: Piskulic Laura , Racca Liliana , Bottai Hebe , Leiva Mercedes
Published: January 2006

This article presents two different approaches to studying the accuracy and precision of a measurement.
Exploring Correlation Coefficients with Golf Statistics
Authors: Quinn Robert J
Published: January 2006

This article explores the relationships between several pairs of statistics kept on professional golfers on the PGA tour. Specifically, two measures related to the player's ability to drive the ball are compared as are two measures related to the player's ability to putt. An additional analysis is made between one statistic related to putting and another that measures how effectively the player tends to reach the green. An analysis of which statistic has the most impact on a player's score is also included. The article concludes with an interesting extension relating the statistics of professionals to the performance of an amateur golfer.
Height, Foot Length and Threat to Woodland: Positive Learning from Pupil Relevant Data
Authors: Turner Claire
Published: January 2006

This article shows how the CensusAtSchool project can be implemented in the classroom to make data handling much more real and relevant. It includes full lesson plans and notes on what the pupils achieved.

Editor's Note

The lesson plans for this article are provided in figure 4, which has been placed at the end of the article for convenience. The plans are based directly on CensusAtSchool material.

Overview of Year 9 Project: Lesson Plans.

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Reasoning with Data – Time for a Rethink?
Authors: Nicholson James , Ridgway Jim , McCusker Sean
Published: January 2006

Reasoning with data is already pervasive in society, and its importance as a life skill is increasing. We argue that the current statistics curriculum in the United Kingdom at the secondary level does not prepare our young people adequately, and suggest ways in which it could be improved.
Relationship of deep white matter hyperintensities and cerebral blood flow in severe carotid artery stenosis
Authors: Patankar T. , Widjaja E. , Chant H. , McCollum C. , Baldwin R. , Jeffries S. , Sutcliffe C. , Burns A. , Jackson A.
Published: January 2006

Leukoaraiosis (LA) has been associated with abnormalities of both large and small blood vessels. This study attempts to clarify the pathogenesis of LA by testing the hypothesis that increased frequency of LA with occlusive extra‐cranial arterial disease results directly from global reduction in cerebral blood flow (CBF). Thirty‐five normal subjects and 55 patients with carotid stenosis (>70%) were studied using MR. CBF was measured using phase contrast MR angiography and LA was scored using previously validated scoring system. Patients were divided into those with evidence of previous infarction on MRI and those without. LA was more severe in patients than in normal subjects (P < 0.01) and correlated with age in normal subjects but not in patients. CBF in patients with (809 ± 214 ml/min) and without infarction (mean 792 ± 181 ml/min) was significantly lower than in normal subjects (mean 1073 ± 194 ml/min). There was no correlation between the severity of LA and measured CBF in any group. The severity of LA is greater in patients with severe carotid stenosis but is not correlated to reductions in CBF. This suggests that microvascular abnormality is the dominant pathogenetic factor in LA even in the presence of severe stenotic/occlusive large vessel disease.
Functional decline in frail community‐dwelling stroke patients
Authors: Landi F. , Onder G. , Cesari M. , Zamboni V. , Russo A. , Barillaro C. , Bernabei R. ,   The Silvernet‐HC study group
Published: January 2006

Patients who suffer a stroke event are at high risk of functional decline after the post‐acute rehabilitation period. The aim of the present study was the evaluation of factors associated with functional decline in a large sample of older patients with stroke living in the community. The study population consisted of all patients admitted to home care programs after a post‐acute rehabilitation program – with at least 1 year of follow‐up – in twenty‐two Italian Home Health Agencies from 2000 to 2002 (n =1338). For the present study we selected 355 (26%) patients with diagnosis of stroke. After 1 year of in‐home care program, 149 out of 355 stroke survivors (42%) had presented a worsening in the activities of daily living (ADL) scale score. In the final adjusted model, patients with cognitive impairment (OR 2.59, 95% CI, 1.45–4.64), pressure ulcer (OR 2.74, 95% CI, 1.45–5.18), urinary incontinence (OR 1.64, 95% CI, 1.01–3.29), or hearing impairment (OR 1.83, 95% CI, 1.02–3.29) were more likely to significantly decline in physical functioning after a period of 1 year in‐home care program. Our study documents that functional decline of stroke patients was largely dependent on specific subjects’ clinical characteristics. Three of four concomitant disabling conditions associated in our sample with functional decline – pressure ulcer, urinary incontinence, hearing – can be prevented and eventually treated or modified. Appropriate post‐acute rehabilitation programs and adequate home care interventions focused on the prevention and treatment of these conditions might be correlated to better outcomes in older post‐stroke patients.
Adult abdominal migraine: a new syndrome or sporadic feature of migraine headache? A case report
Authors: D'Onofrio F. , Cologno D. , Buzzi M. G. , Petretta V. , Caltagirone C. , Casucci G. , Bussone G.
Published: January 2006

Abdominal migraine is one of the variants of migraine headache typically occurring in children and coded as 1.3.2 in the revised edition of IHS classification within the group ‘Childhood periodic syndromes that are commonly precursors of migraine’. The affected children frequently develop typical migraine later in their life. We report a case of a 23 years old woman affected by attacks of recurrent abdominal pain accompanied by migraine. Abdominal pain attacks started in the adolescence and persisted without headache until the patient was 21. At this time, she experienced migraine pain accompanied by nausea, photophobia and phonophobia and associated to acute abdominal pain. Neuroimaging investigations and laboratory testing excluded any underlying organic disease. Complete remission of abdominal attacks was obtained during 4‐month treatment period with pizotifen. Attacks fulfil IHS diagnostic criteria for ‘abdominal migraine’, although of late onset. This case report suggests that ‘abdominal migraine’ is a migraineous disorder to be hypothesized in adult patients after having disclosed any organic disease. As reported in the literature, ‘adult abdominal migraine’ is a sporadic migraine subtype in adult patients and it is not to be considered as a new migraineous syndrome.
Influence of melatonin on fatigue severity in patients with chronic fatigue syndrome and late melatonin secretion
Authors: van Heukelom R. O. , Prins J. B. , Smits M. G. , Bleijenberg G.
Published: January 2006

The effect of melatonin, a chronobiotic drug, was explored in 29 patients with chronic fatigue syndrome (CFS) and Dim Light Melatonin onset (DLMO) later than 21.30 hours, reflective of delayed circadian rhythmicity. The patients took 5 mg of melatonin orally, 5 h before DLMO during 3 months. Their responses to the checklist individual strength (CIS), a reliable questionnaire measuring the severity of personally experienced fatigue, were assessed twice with a 6‐week interval immediately before the treatment and once after 3 months treatment. In the pre‐treatment period the fatigue sub‐score improved significantly. After treatment, the total CIS score and the sub‐scores for fatigue, concentration, motivation and activity improved significantly. The sub‐score fatigue normalized in two of the 29 patients in the pre‐treatment period and in eight of 27 patients during treatment. This change was significant. In the patients with DLMO later than 22.00 hours (n = 21) the total CIS score and the sub‐scores for fatigue, concentration and activity improved significantly more than in the patients (n = 8) with DLMO earlier than 22.00 hours. Melatonin may be an effective treatment for patients with CFS and late DLMO, especially in those with DLMO later than 22.00 hours.
Aging and oxidative stress in progressive supranuclear palsy
Authors: Aoyama K. , Matsubara K. , Kobayashi S.
Published: January 2006

Progressive supranuclear palsy (PSP) is a neurodegenerative disorder, which may possibly be induced by oxidative stress. However, the age‐related alteration of the endogenous antioxidant system is not well understood. To better understand this, we measured Cu/Zn‐superoxide dismutase (SOD), glutathione peroxidase (GPx), and 4‐hydroxynonenal (HNE)‐conjugated GPx in cerebrospinal fluid of PSP patients by enzyme linked immunosorbent assay. A significant increase in the Cu/Zn‐SOD level was detected in PSP group compared with controls. The levels of Cu/Zn‐SOD and GPx in PSP group showed positive correlations with age. Two‐thirds of total GPx was present as the HNE‐conjugated form with positive correlation in PSP group. In conclusion, the endogenous antioxidant system of PSP patients appears to be activated with aging, however, it might be unable to function effectively because of conjugation with HNE.
Repeat intrathecal triamcinolone acetonide application is beneficial in progressive MS patients
Authors: Hoffmann V. , Kuhn W. , Schimrigk S. , Islamova S. , Hellwig K. , Lukas C. , Brune N. , Pöhlau D. , Przuntek H. , Müller T.
Published: January 2006

Available immunomodulatory and conventional steroid treatment regimens provide a limited symptomatic benefit for patients with progressive multiple sclerosis (MS). We performed an open trial on the short‐term efficacy of repeated intrathecal application of the sustained release steroid triamcinolone acetonide (TCA) in 27 progressive MS patients. Six TCA administrations, performed every third day, reduced the Expanded Disability Status Scale (EDSS) score [initial: 5.4 ± 1.3, 3–7.5 (mean ± SD, range); end: 4.9 ± 1.1; 2.5–6.5; P < 0.001] and significantly increased the walking distance and speed in particular after the fourth TCA injection. Concomitantly serially determined cerebrospinal fluid (CSF) markers of cell injury, neuron‐specific enolase, total τ‐protein, S‐100, and β‐amyloid did not significantly change within the interval of TCA treatment. No serious side effects appeared. We conclude that repeat intrathecal injection of 40 mg TCA provides a substantial benefit in progressive MS patients with predominant spinal symptoms and does not alter CSF markers of neuronal cell injury.
A recommended treatment algorithm in relapsing multiple sclerosis: report of an international consensus meeting
Authors: Karussis D. , Biermann L. D. , Bohlega S. , Boiko A. , Chofflon M. , Fazekas F. , Freedman M. , Gebeily S. , Gouider R. , Havrdova E. , Jakab G. , Karabudak R. , Miller A. ,   the International Working Group for Treatment Optimization in MS
Published: January 2006

An International Working Group for Treatment Optimization in MS met to recommend evidence‐based therapeutic options for the management of suboptimal responses or intolerable side‐effects in patients treated with disease‐modifying drugs (DMDs) for multiple sclerosis (MS). Several DMDs are now available for the treatment of MS that have been shown to alter the clinical course of the disease by decreasing disease activity and delaying the progression of disability. Nevertheless, many patients continue to experience disease activity whilst on treatment, and recommendations have been made on how the success of therapy in an individual patient can be assessed. However, even after having identified criteria for a suboptimal response to current treatments, clinicians require guidance on how to improve the outcomes. This report summarizes the conclusions from a workshop at which this issue was addressed. We suggest treatment pathways for optimizing therapy for those patients with suboptimal responses to DMDs, and therapeutic options for patients with unacceptable side‐effects on their current therapy.
A 9‐year review of dystonia from a movement disorders clinic in Singapore
Authors: Jamora R. D. G. , Tan A. K. Y. , Tan L. C. S.
Published: January 2006

The clinical features of dystonia have not been evaluated in Southeast Asia. We therefore investigated the clinical spectrum and characteristics of dystonia in Singapore, a multi‐ethnic Southeast Asian country comprising 77% Chinese, 14% Malays, and 8% Indians. We identified all dystonia patients from the Movement Disorders database and Botulinum Toxin clinic between 1995 and November 2004. Their medical records were reviewed to verify the diagnosis of dystonia and obtain demographic and clinical data using a standardized data collection form. A total of 119 (73%) patients had primary dystonia whilst 45 (27%) had secondary dystonia. There were 77% Chinese, 9% Malays, and 8% Indians. The most common focal dystonia were cervical dystonia (47%), writer's cramp (32%), and blepharospasm (11%). There was no significant difference in the distribution of dystonia between the different races. Males were noted to have earlier onset of dystonia overall. There was a significant male predominance in primary dystonia overall (M:F 1.6:1, P = 0.008) and in the subgroup of focal dystonia (M:F 1.6:1, P = 0.037). This contrasts with previous studies that found a female predominance. The role of genetic, hormonal, and environmental factors and their interactions need to be investigated to better understand the gender differences in the occurrence of dystonia.
Cerebral blood flow velocity changes during meaningful and meaningless gestures – a functional transcranial Doppler study
Authors: Matteis M. , Federico F. , Troisi E. , Pasqualetti P. , Vernieri F. , Caltagirone C. , Petrosini L. , Silvestrini M.
Published: January 2006

The aim of the study was to use functional transcranial Doppler to investigate the possibility of revealing different activation patterns during healthy subjects’ performance of meaningful and meaningless actions. Mean flow velocity (MFV) changes were recorded in middle cerebral arteries (MCAs) of 26 normal subjects during a rest phase and during performance of meaningful and meaningless actions. The meaningful task consisted of pouring sugar into a cup with a teaspoon. The meaningless action was an arm movement similar to that necessary for pouring sugar in a cup but without any tool and thus without a goal. Performing actions with or without meaning was associated with different patterns of MFV changes, as documented by the triple interaction condition × performing arm × side of recording [F(1, 25) = 10.977; P = 0.003]. During the meaningful action, MFV in MCAs increased significantly more than during the meaningless action. During the meaningless action, the MFV increase was significantly higher in the contralateral than in the ipsilateral MCA to the arm performing the task and the meaningful action determined a bilateral MFV increase only when the task was performed with the left arm. When the same task was performed with the right arm, the MFV increase was significantly higher in the contralateral than in the ipsilateral MCA. These findings suggest that the content of an action can influence MFV changes and further confirm the usefulness of transcranial Doppler in neuropsychological investigation.
Tryptophan metabolism and oxidative stress in patients with chronic brain injury
Authors: Mackay G. M. , Forrest C. M. , Stoy N. , Christofides J. , Egerton M. , Stone T. W. , Darlington L. G.
Published: January 2006

The kynurenine pathway generates the excitotoxic N‐methyl‐d‐aspartate receptor agonist, quinolinic acid and the glutamate antagonist, kynurenic acid, as well as free‐radical generators. We investigated the status of the pathway following severe brain injury sustained at least 1 year previously in 15 patients compared with controls. At baseline, patients with brain injury showed increased levels of neopterin, erythrocyte sedimentation rate, C‐reactive protein and peroxidation products in the blood compared with controls, indicating persistent inflammation and oxidative stress. At baseline and following tryptophan depletion, more tryptophan was converted to kynurenine in patients than controls, but less kynurenine was converted into the neuroprotectant, kynurenic acid. This suggests that neuroprotection by kynurenic acid may be inadequate in brain‐damaged patients even many years after injury. On tryptophan loading, patients metabolized more kynurenine into kynurenic acid than controls, a process which may be neuroprotective. In addition, lower levels of 3‐hydroxykynurenine and 3‐hydroxyanthranilic acid in patients after tryptophan loading should be protective since these compounds generate free radicals. The results suggest that for brain‐damaged patients, increased activation of the kynurenine pathway, oxidative stress and raised levels of inflammation continue many years after the original insult, possibly contributing to the continuing cerebral dysfunction in these patients.
The corticobasal syndrome triggered by central pontine myelinolysis
Authors: Shamim A. , Siddiqui B. K. , Josephs K. A.
Published: January 2006

Single case reports have described movement disorders including parkinsonism, dystonia and chorea, but not corticobasal syndrome as a consequence of central pontine and extrapontine myelinolysis. We report a case of a 61‐year‐old woman who developed progressive asymmetric parkinsonism with ideomotor apraxia and cortical sensory deficits following central pontine myelinolysis.
A 24‐week, double‐blind, placebo‐controlled study of three dosages of Cerebrolysin in patients with mild to moderate Alzheimer's disease
Authors: Alvarez X. A. , Cacabelos R. , Laredo M. , Couceiro V. , Sampedro C. , Varela M. , Corzo L. , Fernandez‐Novoa L. , Vargas M. , Aleixandre M. , Linares C. , Granizo E. , Muresanu D. , Moessler H.
Published: January 2006

Cerebrolysin (Cere) is a compound with neurotrophic activity shown to be effective in Alzheimer's disease in earlier trials. The efficacy and safety of three dosages of Cere were investigated in this randomized, double‐blind, placebo‐controlled, study. Two hundred and seventy‐nine patients were enrolled (69 Cere 10 ml; 70 Cere 30 ml; 71 Cere 60 ml and 69 placebo). Patients received iv infusions of 10, 30, 60 ml Cere or placebo 5 days/week for the first 4 weeks and thereafter, two iv infusions per week for 8 weeks. Effects on cognition and clinical global impressions were evaluated 4, 12 and 24 weeks after the beginning of the infusions using the CIBIC+ and the modified Alzheimer's Disease Assessment Scale (ADAS)‐cog. At week 24, significant improvement of cognitive performance on the ADAS‐cog (P = 0.038) and global function (CIBIC+; P > 0.001) was observed for the 10 ml dose. The 30 and 60 ml doses showed significant improvement of the global outcome but failed to show significant improvement of cognition. The results are consistent with a reversed U‐shaped dose–response relationship for Cere. The percentage of patients reporting adverse events was similar across all study groups. Cere treatment was well tolerated and led to significant, dose‐dependent improvement of cognition and global clinical impression.
EFNS guidelines on management of neurological problems in liver transplantation
Authors: Guarino M. , Benito‐Leon J. , Decruyenaere J. , Schmutzhard E. , Weissenborn K. , Stracciari A.
Published: January 2006

Neurological impairment after orthotopic liver transplantation (OLT) is common and represents a major source of morbidity and mortality. The diagnosis and management of neurological problems occurring after OLT are difficult and evidence‐based guidelines for this task are currently lacking. A Task Force was set up under the auspices of the European Federation of Neurological Societies to devise guidelines to prevent and manage neurological problems in OLT. We selected six major neurological problems and approached them combining an evidence‐based scientific literature analysis with a search of consensus by means of a Delphi process. Search results were translated into a series of recommendations constituting a basis for better care of patients with neurological complications after OLT.
Evaluating the IHS Criteria for Cluster Headache – a Comparison between Patients Meeting all Criteria and Patients Failing One Criterion
Authors: van Vliet JA , Eekers PJE , Haan J , Ferrari MD ,   for the Dutch RUSSH Study Group
Published: January 2006

Cluster headache (CH) is diagnosed according to criteria of the International Headache Society (IHS), but, in clinical practice, these criteria seem too restrictive. As part of a nation-wide study, we identified a group of patients who met all criteria minus one (IHS-CH-1), and assessed in which way they differed from CH patients meeting all criteria (IHS-CH). We performed a nation-wide questionnaire study for CH and CH-like syndromes, including questions based on the IHS criteria, and additional features such as restlessness during attacks, nocturnal onset of attacks, circadian rhythmicity of attacks and response to treatment. IHS-CH and IHS-CH-1 patients were compared. Of 1452 responders to two questionnaires, 1163 were IHS-CH and 289 were IHS-CH-1. The majority of the IHS-CH-1 patients were classified as such because their attacks exceeded 3 h (64%, median attack duration: 5 h), or came in a frequency of less than 1 per 2 days (16%). Age at onset was similar between the groups. The male to female ratio was 3.7 : 1 in the IHS-CH group and around 1.6 : 1 in the IHS-CH-1 groups ( P < 0.005). Patients with attacks exceeding 3 h less often reported a circadian rhythmicity (IHS-CH-1: 49%, IHS-CH: 64%), episodic periodicity (IHS-CH-1: 65%, IHS-CH: 78%), nocturnal attacks (IHS-CH-1: 67%, IHS-CH: 78%), smoking (IHS-CH-1: 90%, IHS-CH: 80%) and restlessness during attacks (IHS-CH-1: 64%, IHS-CH: 76%) than IHS-CH patients ( P < 0.005). Photo- or phono-phobia (IHS-CH-1: 67%, IHS-CH: 54%) and nausea (IHS-CH-1: 38%, IHS-CH: 27%) were more frequently reported by patients who reported to have attacks exceeding 3 h ( P < 0.005). Similar proportions reported effect of verapamil on their attacks (IHS-CH-1: 54%, IHS-CH 61%). We conclude that average attack duration exceeding 3 h was frequently the reason for not fulfilling IHS CH criteria. Symptoms often accompanying CH such as restlessness, nocturnal attacks and an episodic attack pattern were relatively frequently present in IHS-CH-1 patients with longer attacks. These patients may therefore be diagnosed with CH. Attack frequency may not be a useful criterion for the diagnosis of CH. The upper limit of 3 h should be increased in future diagnostic criteria.
Preference for Rizatriptan 10-mg Wafer vs. Eletriptan 40-mg Tablet for Acute Treatment of Migraine
Authors: Láinez MJA , Evers S , Kinge E , Allais G , Allen C , Rao NA , Massaad R , Lis K
Published: January 2006

Preference is a composite, patient-oriented endpoint incorporating efficacy, tolerability, formulation, and convenience of medications. The objective of this study was to compare patient preference for rizatriptan 10-mg wafer vs. eletriptan 40-mg tablet for acute treatment of migraine. In this multicentre, open-label, two-period, crossover study, out-patients were randomly assigned to treat the first of two moderate to severe migraines with rizatriptan or eletriptan and the second with the alternate therapy. Patients completed diary assessments at baseline and up to 24 h after taking study medication. At the last visit, patients completed a psychometrically validated preference questionnaire. A total of 372 patients (mean age 38 years, 85% female) treated two migraine attacks, and 342 patients (92%) expressed a preference for treatment. Significantly more ( P ≤ 0.001) patients preferred rizatriptan 10-mg wafer [61.1%; 95% confidence interval (CI) 55.7, 66.3] to eletriptan 40-mg tablet (38.9%; 95% CI 33.7, 44.3). The most common reason given for preference of either treatment was speed of headache relief. At 2 h, 80% and 69% of patients reported that rizatriptan and eletriptan, respectively, was convenient or very convenient to take (mean convenience score 1.99 vs. 2.31, respectively; P ≤ 0.001). Both triptans were well tolerated. In this head-to-head study designed to evaluate global patient preference, significantly more patients preferred the rizatriptan 10-mg wafer to the eletriptan 40-mg tablet for acute treatment of migraine. The single most important reason for preference was speed of relief, consistent with results from previous preference studies.
PGH2‐derived levuglandin adducts increase the neurotoxicity of amyloid β1–42
Authors: Boutaud Olivier , Montine Thomas J. , Chang Lei , Klein William L. , Oates John A.
Published: January 2006

The body of evidence indicating that oligomers of amyloid β1−42 (Aβ1−42) produce toxicity to neurons, together with our demonstration that prostaglandin H2 (PGH2) oligomerizes amyloid β1−42, led to the examination of the neurotoxicity of amyloid β1−42 treated with PGH2. The neurotoxic effects of Aβ1−42 incubated with PGH2 was examined in primary cultures of cerebral neurons of mice, monitoring the reduction of 3‐(4,5‐dimethylthiazole‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) as an indicator of cell toxicity. Whereas Aβ1−42 itself, incubated for 24 h, has little or no effect on MTT reduction, Aβ1−42 24 h after exposure to PGH2 produced a marked inhibition of MTT reduction, comparable with the inhibition resulting from Aβ1−42 that has been oligomerized by incubation for 6 days. Similar results were obtained when Aβ1−42 was incubated with levuglandin E2 (LGE2), a reactive aldehyde formed by spontaneous rearrangement of PGH2. The oligomers formed from reaction of Aβ1−42 with LGE2 exhibit immunochemical similarity with amyloid‐derived diffusible ligands (ADDLs), as determined by analysis of the products of reaction of Aβ1−42 with LGE2 using western blotting with an antibody that is selective for ADDLs.
Sialylation enhances the secretion of neurotoxic amyloid‐β peptides
Authors: Nakagawa Kazuhiro , Kitazume Shinobu , Oka Ritsuko , Maruyama Kei , Saido Takaomi C. , Sato Yuji , Endo Tamao , Hashimoto Yasuhiro
Published: January 2006

Alzheimer's disease (AD) is characterized by amyloid‐β peptide (Aβ) deposition in the brain. Aβ is produced by sequential cleavage of amyloid precursor protein (APP) by β‐secretase (BACE1: β‐site APP‐cleaving enzyme 1) and γ‐secretase. Previously, we demonstrated that BACE1 also cleaves β‐galactoside α2,6‐sialyltransferase (ST6Gal‐I) and down‐regulates its transferase activity. Here, we report that overexpression of ST6Gal‐I in Neuro2a cells enhanced α2,6‐sialylation of endogenous APP and increased the extracellular levels of its metabolites [Aβ by two‐fold, soluble APPβ (sAPPβ) by three‐fold and sAPPα by 2.5‐fold). Sialylation‐deficient mutant (Lec‐2) cells secreted half as much Aβ as wild‐type Chinese hamster ovary (CHO) cells. Furthermore, wild‐type CHO cells showed enhanced secretion of the APP metabolites upon ST6Gal‐I overexpression, whereas Lec‐2 cells did not, indicating that the secretion enhancement requires sialylation of cellular protein(s). Secretion of metabolites from a mutant APP (APP‐Asn467,496Ala) that lacked N‐glycosylation sites was not enhanced upon ST6Gal‐I overexpression, suggesting that the N‐glycans on APP itself are required for the enhanced secretion. In the mouse brain, the amount of α2,6‐sialylated APP appeared to be correlated with the sAPPβ level. These results suggest that sialylation of APP promotes its metabolic turnover and could affect the pathology of AD.
Differential regulation of corticotropin releasing factor 1α receptor endocytosis and trafficking by β‐arrestins and Rab GTPases
Authors: Holmes Kevin D. , Babwah Andy V. , Dale Lianne B. , Poulter Michael O. , Ferguson Stephen S. G.
Published: January 2006

The corticotropin releasing factor (CRF) type 1α receptor, a member of the G protein‐coupled receptor (GPCR) subfamily B, is involved in the aetiology of anxiety and depressive disorders. In the present study, we examined the internalization and trafficking of the CRF1α receptor in both human embryonic kidney (HEK)293 cells and primary cortical neurons. We found that CRF1α receptor activation leads to the selective recruitment of β‐arrestin2 in both HEK293 cells and neurons. We observed distinct distribution patterns of CRF1α receptor and β‐arrestin2 in HEK293 cells and cortical neurons. In HEK293 cells, β‐arrestin2‐green fluorescent protein (GFP) co‐localized with CRF1α receptor in vesicles at the plasma membrane but was dissociated from the receptor in endosomes. In contrast, in primary cortical neurons, β‐arrestin2 and CRF1α receptor were internalized in distinct endocytic vesicles. By bioluminescence resonance energy transfer, we demonstrated that β‐arrestin2 association with CRF1α receptor was increased in cells transfected with G protein‐coupled receptor kinase (GRK)3 and GRK6 and decreased in cells transfected with GRK2 and GRK5. In both HEK293 cells and cortical neurons, internalized CRF1α receptor transited from Rab5‐positive early endosomes to Rab4‐positive recycling endosomes and was not targeted to lysosomes. However, CRF1α receptor resensitization was blocked by the overexpression of wild‐type, but not dominant‐negative, Rab5 and Rab4 GTPases. Taken together, our results suggest that β‐arrestin trafficking differs between HEK293 cells and neurons, and that CRF1α receptor resensitization is regulated in an atypical manner by Rab GTPases.
Substrate‐mediated enhancement of phosphorylated tyrosine hydroxylase in nigrostriatal dopamine neurons: evidence for a role of α‐synuclein
Authors: Drolet Robert E. , Behrouz Bahareh , Lookingland Keith J. , Goudreau John L.
Published: January 2006

Tyrosine hydroxylase (TH) protein, phosphorylated at serine‐40, serine‐31 and serine‐19, and enzyme catalytic activity were compared under basal conditions and in activated nigrostriatal dopamine (NSDA) neurons of wild‐type and homozygous α‐synuclein knockout mice. Mice were injected with the D2 antagonist raclopride to stimulate NSDA neuronal activity in the presence or absence of supplementall‐tyrosine. There was no difference in phosphorylated TH levels or TH catalytic activity between wild‐type and α‐synuclein knockout mice under basal conditions or following raclopride‐induced acceleration of NSDA activity. In wild‐type animals, tyrosine administration potentiated the raclopride‐induced increase in phosphorylated TH and enzyme activity. However, tyrosine administration did not enhance phosphorylated TH levels or enzyme catalytic activity in raclopride‐stimulated NSDA neurons in α‐synuclein knockout mice. These findings suggest that α‐synuclein plays a role in the ability of tyrosine to either enhance TH phosphorylation or hinder TH inactivation during accelerated neuronal activity. The present study supports the hypothesis that α‐synuclein functions as a molecular chaperone protein that regulates the phosphorylation state of TH in a substrate and activity‐dependent manner.
Compensation in pre‐synaptic dopaminergic function following nigrostriatal damage in primates
Authors: McCallum S. E. , Parameswaran N. , Perez X. A. , Bao S. , McIntosh J. M. , Grady S. R. , Quik M.
Published: January 2006

Clinical symptoms of Parkinson's disease only become evident after 70–80% reductions in striatal dopamine. To investigate the importance of pre‐synaptic dopaminergic mechanisms in this compensation, we determined the effect of nigrostriatal damage on dopaminergic markers and function in primates. MPTP treatment resulted in a graded dopamine loss with moderate to severe declines in ventromedial striatum (approximately 60–95%) and the greatest reductions (approximately 95–99%) in dorsolateral striatum. A somewhat less severe pattern of loss was observed for striatal nicotinic receptor, tyrosine hydroxylase and vesicular monoamine transporter expression. Declines in striatal dopamine uptake and transporter sites were also less severe than the reduction in dopamine levels, with enhanced dopamine turnover in the dorsolateral striatum after lesioning. The greatest degree of adaptation occurred for nicotine‐evoked [3H]dopamine release from striatal synaptosomes, which was relatively intact in ventromedial striatum after lesioning, despite > 50% declines in dopamine. This maintenance of evoked release was not due to compensatory alterations in nicotinic receptor characteristics. Rather, there appeared to be a generalized preservation of release processes in ventromedial striatum, with K+‐evoked release also near control levels after lesioning. These combined compensatory mechanisms help explain the finding that Parkinson's disease symptomatology develops only with major losses of striatal dopamine.
Increased levels of cyclins D1 and D3 after inhibition of gap junctional communication in astrocytes
Authors: Tabernero Arantxa , Sánchez‐Alvarez Rosa , Medina José M.
Published: January 2006

We showed previously that the inhibition of gap junctional communication in astrocytes increased bromodeoxyuridine (BrdU) incorporation and promoted changes in the metabolic phenotype destined to fulfil the requirements of cell proliferation. In the present study we investigated the changes in the cell cycle of astrocytes promoted by the inhibition of intercellular communication through gap junctions. Thus, the presence of endothelin‐1 and carbenoxolone, two gap junction uncouplers, promoted an increase in the percentage of astrocytes found in the S, G2 and M phases of the cell cycle, with a concomitant decrease in G0 and G1 phases. In addition, the levels of Ki‐67, a protein present during all active phases of the cell cycle but absent from resting cells, increased after the inhibition of gap junctional communication. These effects were not observed when the inhibition of gap junctions was prevented with tolbutamide, indicating that the inhibition of gap junctional communication promotes the entry of astrocytes into the cell cycle. The passage of the cells from a quiescent state to the cell cycle is ultimately regulated by the degree of retinoblastoma phosphorylation. Inhibition of gap junctions increased the phosphorylation of retinoblastoma at Ser 780 but not at Ser 795 or Ser 807/811. In addition, the levels of cyclins D1 and D3 increased, whereas those of p21 and p27 were not significantly modified. Because D‐type cyclins are key regulators of retinoblastoma protein phosphorylation, it is suggested that the phosphorylation of retinoblastoma protein at Ser 780, observed under our experimental conditions, is a consequence of the increase in the levels of cyclins D1 and D3. Our work provides evidence for the involvement of cyclins D1 and D3 as sensors of the inhibition of gap junctional communication in astrocytes.
Identification of amino acid residues important for assembly of GABAAreceptor α1 and γ2 subunits
Authors: Sarto‐Jackson Isabella , Ramerstorfer Joachim , Ernst Margot , Sieghart Werner
Published: January 2006

Comparative models of GABAAreceptors composed of α1β3γ2 subunits were generated using the acetylcholine‐binding protein (AChBP) as a template and were used for predicting putative engineered cross‐link sites between the α1 and the γ2 subunit. The respective amino acid residues were substituted by cysteines and disulfide bond formation between subunits was investigated on co‐transfection into human embryonic kidney (HEK) cells. Although disulfide bond formation between subunits could not be observed, results indicated that mutations studied influenced assembly of GABAAreceptors. Whereas residue α1A108 was important for the formation of assembly intermediates with β3 and γ2 subunits consistent with its proposed location at the α1(+) side of GABAAreceptors, residues γ2T125 and γ2P127 were important for assembly with β3 subunits. Mutation of each of these residues also caused an impaired expression of receptors at the cell surface. In contrast, mutated residues α1F99C, α1S106C or γ2T126C only impaired the formation of receptors at the cell surface when co‐expressed with subunits in which their predicted interaction partner was also mutated. These data are consistent with the prediction that the mutated residue pairs are located close to each other.
Dynamic regulation of fibroblast growth factor 2 (FGF‐2) gene expression in the rat brain following single and repeated cocaine administration
Authors: Fumagalli Fabio , Di Pasquale Laura , Racagni Giorgio , Riva Marco Andrea
Published: January 2006

Administration of drugs of abuse can produce long‐lasting effects on brain function, which involve modifications at neurotransmitter level as well as changes in proteins important for structural alterations of selected brain regions. The contribution of trophic factors in these events has so far been underestimated. Here, we demonstrate that a single cocaine injection selectively up‐regulated fibroblast growth factor 2 (FGF‐2) mRNA levels in the striatum and prefrontal cortex within 2 h, an effect that vanished by 24 h. However, prolonged exposure (5 or 14 days) to cocaine treatment produced an enduring elevation of FGF‐2 mRNA levels that was evident 72 h after the last injection in the prefrontal cortex and could even persist for 14 days in the striatum, raising the possibility that cocaine treatment primes the brain, resulting in longer‐lasting FGF‐2 up‐regulation in regions that are highly innervated by dopaminergic projections. The expression of FGF‐2 was also significantly increased in the midbrain following acute or 5‐day injection, suggesting that modulation of FGF‐2 biosynthesis in dopamine‐producing cells occurs only during early stages of cocaine exposure. Our results point to important mechanistic conclusions as to how cocaine alters FGF‐2 expression. Whereas cocaine‐induced changes in FGF‐2 gene expression following a single injection could be ascribed to increased release of transmitters (mainly dopamine), enhanced FGF‐2 gene expression following repeated administration identifies the trophic factor as part of the adaptive changes set in motion by cocaine.