bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantitative evaluation of mirror movements in adults with focal brain lesions
Authors: Uttner I. , Mai N. , Esslinger O. , Danek A.
Published: November 2005

Mirror movements (MM), involuntary movements of homologous muscles opposite to unilateral limb activity, decrease in the course of motor development, but may reappear in adults after brain damage. To better characterize this type of acquired MM, grip forces of 36 healthy subjects and 35 patients suffering from focal brain lesions were compared. Holding force transducers in a pinch grip between thumb and index fingers of each hand, subjects had to repeatedly change the grip force in one hand, whilst the other (mirror) hand just had to prevent the manipulandum from dropping. In a second task, force changes had to be produced either in a symmetric or in an antiparallel manner. No significant group differences between patients and controls in the extent of coupling were found. During unimanual squeezing, only six patients had a co‐activation in the pathologic range. Whilst performing bimanual asymmetric grip force changes, pathologic coupling was seen only in five patients. No association was found between the presence of pathologic MM and clinical or neuroanatomical features. Brain lesions in adults seem only rarely to be associated with pathologic MM. They might be non‐specific and not related to the characteristics of the lesion.
Toward a more efficient and effective neurologic examination for the 21st century*
Authors: Glick T. H.
Published: November 2005

Practice pressures and quality improvement require greater efficiency and effectiveness in the neurologic examination. I hypothesized that certain ‘marginal’ elements of the examination rarely add value and that ‘core’ elements, exemplified by the plantar response (Babinski), are too often poorly performed or interpreted. I analyzed 100 published, neurologic clinicopathologic conferences (CPCs) and 180 ambulatory neurologic consultations regarding 13 hypothetically ‘marginal’ examination components (including ‘frontal’ reflexes, olfaction, jaw strength, corneal reflex, etc.); also, 120 exams on medical inpatients with neurologic problems, recording definitive errors. I surveyed the recalled practices of 24 non‐neurologists and reviewed the literature for relevant data or guidance. In the CPCs the ‘marginal’ elements of the examination were rarely provided, requested, or used diagnostically, nor did they contribute in the 180 ambulatory consultations. In the chart review errors and omissions dominated testing of plantar responses, with missed Babinski signs in 14% of all cases and 77% of patients with Babinski signs. House officers harbored unrealistic expectations for performance of ‘marginal’ examination elements. Most textbooks omit detailed guidance (and none cite evidence) on achieving greater efficiency. Exams should be streamlined, while improving ‘core’ skills. Neurologists should apply evidence to update the exam taught to students and non‐neurologists.
Paroxysmal intracranial hypertension
Authors: Kidd D. , Wilson P. L. , Unwin B.
Published: November 2005

We present the case of a man who presented with headache and severe papilloedema which was caused not by chronic intracranial hypertension but by paroxysms of raised intracranial pressure, and we speculate what relationship this disorder has to idiopathic intracranial hypertension.
Pharmacologic Evidence for Abnormal Thalamocortical Functioning in GABAA Receptor β3 Subunit–Deficient Mice, a Model of Angelman Syndrome
Authors: Handforth Adrian , DeLorey Timothy M. , Homanics Gregg E. , Olsen Richard W.
Published: November 2005

Summary:  Purpose:γ‐Aminobutyric acid receptor (GABAAr) subunit β3–deficient mice model Angelman syndrome by displaying impaired learning, abnormal EEG with interictal spikes and slowing, myoclonus, and convulsions. The β3‐subunit deficiency causes a failure of intrathalamic reticular nucleus inhibition, leading to abnormally synchronized thalamocortical oscillations. We postulated that this pathophysiology underlies the abnormal cortical EEG and triggers interictal spikes and seizures, but extrathalamic regions also contribute to interictal spikes and seizures, so that the EEG slowing should reveal an absence‐like response profile, whereas spikes and seizures have dual responsiveness to absence and partial‐seizure drugs.

Methods: Recording electrodes were implanted over the parietal cortices of wild‐type, heterozygotes, and homozygous null mice. In each experiment, EEG was recorded for 45 min, either drug or vehicle administered, and EEG recorded for another 3 h. Each EEG was scored for slow‐wave activity, interictal spikes, and seizures by a reader blinded to treatments.

Results: Interictal spiking and percentage of time in EEG slowing in heterozygotes were increased by the proabsence drug baclofen (GABAB‐receptor agonist), whereas CGP 35348 (GABAB‐receptor antagonist) had the opposite effect. The antiabsence drug ethosuximide markedly suppressed EEG slowing and interictal spiking in heterozygote and null mice. Broad‐spectrum clonazepam and valproate were more effective on interictal spiking than on EEG slowing, and fosphenytoin suppressed only interictal spiking.

Conclusions: The results suggest that this model of Angelman syndrome, although not expressing typical absence seizures, is characterized by hypersynchronous thalamocortical oscillations that possess absence‐like pharmacologic responsiveness and promote EEG slowing, interictal spikes, and convulsive seizures.
Epileptogenesis and Reduced Inward Rectifier Potassium Current in Tuberous Sclerosis Complex‐1–Deficient Astrocytes
Authors: Jansen Laura A. , Uhlmann Erik J. , Crino Peter B. , Gutmann David H. , Wong Michael
Published: November 2005

Summary:  Purpose: Individuals with tuberous sclerosis complex (TSC) frequently have intractable epilepsy. To gain insights into mechanisms of epileptogenesis in TSC, we previously developed a mouse model of TSC with conditional inactivation of the Tsc1 gene in glia (Tsc1GFAPCKO mice). These mice develop progressive seizures, suggesting that glial dysfunction may be involved in epileptogenesis in TSC. Here, we investigated the hypothesis that impairment of potassium uptake through astrocyte inward rectifier potassium (Kir) channels may contribute to epileptogenesis in Tsc1GFAPCKO mice.

Methods: Kir channel function and expression were examined in cultured Tsc1‐deficient astrocytes. Kir mRNA expression was analyzed in astrocytes microdissected from neocortical sections of Tsc1GFAPCKO mice. Physiological assays of astrocyte Kir currents and susceptibility to epileptiform activity induced by increased extracellular potassium were further studied in situ in hippocampal slices.

Results: Cultured Tsc1‐deficient astrocytes exhibited reduced Kir currents and decreased expression of specific Kir channel protein subunits, Kir2.1 and Kir6.1. mRNA expression of the same Kir subunits also was reduced in astrocytes from neocortex of Tsc1GFAPCKO mice. By using pharmacologic modulators of signalling pathways implicated in TSC, we showed that the impairment in Kir channel function was not affected by rapamycin inhibition of the mTOR/S6K pathway, but was reversed by decreasing CDK2 activity with roscovitine or retinoic acid. Last, hippocampal slices from Tsc1GFAPCKO mice exhibited decreased astrocytic Kir currents, as well as increased susceptibility to potassium‐induced epileptiform activity.

Conclusions: Impaired extracellular potassium uptake by astrocytes through Kir channels may contribute to neuronal hyperexcitability and epileptogenesis in a mouse model of TSC.
Brain Perfusion Following Single Seizures
Authors: Leonhardt Georg , De Greiff Armin , Weber Johannes , Ludwig Tanja , Wiedemayer Helmut , Forsting Michael , Hufnagel Andreas
Published: November 2005

Summary:  Purpose: The aim of this study was to assess the regional relative interictal and postictal perfusion changes in temporal and parietal lobe epilepsy.

Methods: We investigated interictal and postictal magnet resonance perfusion changes in five patients with temporal lobe epilepsy either with hippocampal sclerosis (n = 3) or without (n = 2), and in one patient with extratemporal (parietal lobe) epilepsy. T2*‐weighted single‐shot echo‐planar images were acquired after bolus application of 0.2 mmol/kg gadolinium‐diethylene triamine pentaacetic acid (GD‐DTPA) at baseline and after intervals of 2–12 min, 15–23 min, 28–50 min, 63–72 min, and 180–240 min. The bolus‐peak ratio was calculated in regions of interest in the hippocampus (HIP), parahippocampal gyrus (PHG), thalamus (THA), cortex (COR), and white matter (WM), yielding relative perfusion changes.

Results: Interictally, we found relative hyperperfusion of the ictogenic side in five of six patients in the HIP. Postictally, the perfusion decreased in the HIP by 25–39% as compared to baseline, whereas the PHG showed a reverse pattern. In the late postictal phase, perfusion increased in the HIP again and decreased in the PHG. In the THA, the inter‐ and postictal changes were small (5–19%). COR and WM showed equivocal results.

Conclusion: Postictal relative hypoperfusion in the HIP appears to be associated with the cessation of neuronal ictal discharge, whereas postictal hyperperfusion in the PHG lags behind and may reflect increased metabolism to restore the interictal state of neuronal excitability.
Levetiracetam Efficacy in Epileptic Syndromes with Continuous Spikes and Waves during Slow Sleep: Experience in 12 Cases
Authors: Aeby Alec , Poznanski Nathalie , Verheulpen Denis , Wetzburger Catherine , Van Bogaert Patrick
Published: November 2005

Summary: Purpose:To assess the add‐on efficacy of levetiracetam on the EEG, behavior, and cognition of children with continuous spikes and waves during slow sleep (CSWS).

Methods:Charts of children with behavioral and/or cognitive deterioration associated with CSWS who received levetiracetam at 50 mg/kg/day as add‐on treatment were retrospectively reviewed. Awake and sleep EEG recordings and detailed neuropsychological and behavioral assessments were available at baseline and 2 months after levetiracetam initiation. In children showing clinical and/or electrophysiological improvement after 2 months, levetiracetam was continued with a new evaluation at 1 year.

Results:Twelve patients were included (9 cryptogenic and 3 symptomatic cases). Seven patients (58.3%) showed improvement of EEG record. Among these seven patients, neuropsychological evaluation was improved in three, and in the other four patients, not testable because of severe cognitive impairment, behavior was improved. Two patients improved in neuropsychological evaluation despite the lack of EEG improvement. Eight patients (66.6%) continued levetiracetam treatment after 2 months. After 1 year, four patients were still on levetiracetam, two because sustained effect on EEG and behavior and the two others because improvement in neuropsychological testing despite unchanged EEG. Levetiracetam was discontinued in the other four patients because of neuropsychological or behavioral deterioration associated with CSWS pattern, between 9 and 11 months after treatment initiation.

Conclusions:This retrospective study suggests that levetiracetam has a positive effect on the EEG, the behavior, and the cognition of patients with epilepsy and CSWS. Additional studies are warranted in order to assess the place of this drug in these epileptic conditions.
Taylor‐type Focal Cortical Dysplasia in Infants: Some MRI Lesions Almost Disappear with Maturation of Myelination
Authors: Eltze Christin M. , Chong Wui K. , Bhate Sanjay , Harding Brian , Neville Brian G. R. , Cross J. Helen
Published: November 2005

Summary:  Identification of focal cortical dysplasia (FCD) on magnetic resonance (MR) images of young children with refractory focal epilepsy is important, as surgical resection may offer improvement of seizure control and subsequent developmental progress. However, the MR appearances of malformations of cortical development may change during brain maturation. We report 4 children with refractory focal epilepsy, whose MR images in infancy showed localized cortical and subcortical signal abnormalities (hypointense on T2‐weighted and hyperintense on T1‐weighted images), suggestive of abnormal cortical development. The visibility of these lesions was significantly reduced on later MR images. Subtle blurring of the gray–white matter junction in these areas was the only indicator of cortical abnormality in 3 patients, which was recognized only after comparison with earlier images. Taylor‐type FCD was subsequently confirmed in all patients, following surgical cortical resection of the lesions. MR images performed early within the first year of life in children with epilepsy are important to identify areas of FCD. The appearances of FCD on later scans can be very subtle escaping recognition, and conclusions may be misleading with respect to diagnosis and appropriateness of surgical treatment.
The Prevalence of Autistic Spectrum Disorder in Children Surveyed in a Tertiary Care Epilepsy Clinic
Authors: Clarke Dave F. , Roberts Wendy , Daraksan Mina , Dupuis Annie , McCabe Jane , Wood Halyey , Snead O. Carter , Weiss Shelly K.
Published: November 2005

Summary:  It is well documented that children with autistic spectrum disorder (ASD) have an increased prevalence of seizures; however, studies have not been done to evaluate the prevalence of ASD in children with epilepsy. This comorbidity is important to define as early diagnosis and intervention in some children with ASD has been shown to improve outcome.

Method: Children with epilepsy seen in a tertiary care epilepsy clinic were evaluated using validated autism screening questionnaires (ASQ). In addition, questions about sleep‐related disorders, behavior, seizure characteristics, antiepileptic agents, and body mass index (BMI) were requested. An attempt was then made to determine if there was a correlation between the factors identified and ASD.

Results: Of the 107 questionnaires returned, 97 ASQ's were properly completed and used in this study. Approximately 32% of children fit the ASQ criteria for having ASD. Most children had not been previously diagnosed. Worst behavior and daytime sleepiness was seen in those at greater risk (p < 0.01). Seizures also occurred earlier (approximately 2 years) in children at risk of having ASD.

Conclusion: Though confirmatory diagnostic evaluations are needed, this questionnaire‐based study suggests that children with epilepsy are at greater risk of having ASD, and illustrates the need for more clinical vigilance. Behavioral difficulties and daytime sleepiness identified in these children could potentially affect their ability to learn. It is of interest that the age of seizure onset identified in those at greater risk corresponds with the approximate age of regression identified in some children with ASD.
The Role of Parent and Peer Support in Predicting Adolescent Depression: A Longitudinal Community Study
Authors: Young Jami F. , Berenson Kathy , Cohen Patricia , Garcia Jesenia
Published: November 2005

This study examines whether perceived parent support, peer support, and the interaction between them predict depression symptoms and depression diagnosis 2 years later in a community sample of 389 adolescents. Controlling for Time 1 depression, parent support and anticipated peer support were not independently related to Time 2 depression in either linear or logistic regression analyses. However, there was a significant interaction between the two support variables, suggesting that parent support moderates the relationship between anticipated peer support and depression symptoms and diagnosis. Anticipated peer support is protective among adolescents with high parental support, but may act as a risk factor for adolescents with low parental support. Regarding developmental differences, low anticipated peer support at Time 1 was a stronger predictor of Time 2 depression symptoms among older, compared with younger, adolescents. These findings highlight the importance of parent and peer support in predicting future depression among community adolescents.
Body Image and Self‐Esteem Among Adolescent Girls: Testing the Influence of Sociocultural Factors
Authors: Clay Daniel , Vignoles Vivian L. , Dittmar Helga
Published: November 2005

In Western cultures, girls' self‐esteem declines substantially during middle adolescence, with changes in body image proposed as a possible explanation. Body image develops in the context of sociocultural factors, such as unrealistic media images of female beauty. In a study of 136 U.K. girls aged 11–16, experimental exposure to either ultra‐thin or average‐size magazine models lowered body satisfaction and, consequently, self‐esteem. Self‐esteem was also lower among older than among younger girls. Structural equation modeling showed that this age trend was partially accounted for by a corresponding downward trend in body satisfaction; this, in turn, was fully accounted for by upward age trends in awareness and internalization of sociocultural attitudes toward appearance, and in social comparison with media models. Results support calls for early educational interventions to help girls to deconstruct advertising and media images.
Life Course Heterogeneity in the Transition from Adolescence to Adulthood Among Adolescent Mothers
Authors: Oxford Monica L. , Gilchrist Lewayne D. , Lohr Mary Jane , Gillmore Mary Rogers , Morrison Diane M. , Spieker Susan J.
Published: November 2005

Longitudinal data were used to examine pathways taken by 227 adolescent mothers during the transition from adolescence into adulthood. Latent profile analysis identified three sub‐groups of adolescent mothers from 6 months to 6 years postpartum: a problem‐prone profile (15%), a psychologically vulnerable profile (42%), and a normative profile (43%). Group membership was related to long‐term adult outcomes (adult status markers, health‐risk and deviant behaviors, substance use, mental health, and intimate relationships) when respondents were nearing age 30. The psychologically vulnerable group reported greater health and mental health problems, relational problems, and substance use than the normative profile group. Only the problem‐prone profile group, taken together, reported serious problems in all domains of adult outcomes examined including financial, relational, behavioral, and health and mental health problems. Results confirm the existence of different pathways through adolescent parenthood that are associated with adult functioning 12 years postpartum.
Coping Trajectories from Adolescence to Young Adulthood: Links to Attachment State of Mind
Authors: Seiffge‐Krenke Inge , Beyers Wim
Published: November 2005

The objective of this study was to examine the links between coping and attachment. In a longitudinal study of 112 participants, coping behavior was assessed at five points in time during adolescence (starting at the age of 14 years) and early adulthood. In addition, at the age of 21 years, state of mind regarding current and earlier attachment experiences was assessed by employing the Adult Attachment Interview (AAI). In both adolescence and early adulthood, differences in coping styles were found to be related to differences in attachment. Individuals classified as secure dealt with their problems more actively by using their social network during adolescence and at the age of 21 years. Both secure and dismissing individuals used more internal coping than those with a preoccupied state of mind. Latent growth curve modeling revealed that differences in active and internal coping between secure and insecure individuals applied to the rate of change in these coping styles between 14 and 21 years, with participants in the secure group showing much steeper growth in both coping styles. Only minor differences were found with respect to withdrawal as a coping style. The results represent first evidence that coping trajectories during adolescence and young adulthood are linked with attachment state of mind.
Self‐Competence Mediates Earlier and Later Anxiety in Adolescent Mothers: A 3‐Year Longitudinal Perspective
Authors: Schiefelbein Virginia L. , Susman Elizabeth J. , Dorn Lorah D.
Published: November 2005

Anxiety is prevalent in adolescents and may be particularly problematic in pregnant adolescents. The purpose of this structural equation modeling analysis was to test a biobehavioral model in which postpartum self‐competence mediated pathways from anxiety and cortisol during pregnancy to anxiety 3 years later. Self‐reports of anxiety and self‐competence and salivary cortisol samples were obtained from 78 healthy primiparous and 57 nonpregnant comparison adolescent girls matched for age and socioeconomic status. Assessments were done during the first half of pregnancy, 3–4 weeks after childbirth, and at a 3‐year follow up. For pregnant girls, linkages from initial anxiety to self‐competence to follow‐up anxiety were significant and negative, as hypothesized. Direct and indirect pathways between initial and follow‐up anxiety were significant. Cortisol levels did not predict self‐competence or anxiety. For nonpregnant adolescents, the model fit poorly. Findings suggest self‐competence may play a mediating role in young mothers' anxiety across time.
Multiple Losses, EX ANTE Moral Hazard, and the Implications for Umbrella Policies
Authors: Breuer Michael
Published: November 2005

Abstract

Under certain cost conditions the optimal insurance policy offers full coverage above a deductible, as Arrow and others have shown. However, many insurance policies currently provide coverage against several losses although the possibilities for the insured to affect the loss probabilities by several prevention activities (multiple moral hazard) are substantially different. This article shows that optimal contracts under multiple moral hazard generally call for complex reimbursement schedules. It also examines the conditions under which different types of risks can optimally be covered by a single insurance policy and argues that the case for umbrella policies under multiple moral hazard is limited in practice.
Deterring Fraud: The Role of General Damage Awards in Automobile Insurance Settlements
Authors: Loughran David S.
Published: November 2005

Abstract

Awards for pain and suffering and other noneconomic losses account for over half of all damages awarded under third‐party auto insurance bodily injury settlements. This article hypothesizes that third‐party insurers use general damage awards to reduce the incentive to submit exaggerated claims for specific damages for injuries and lost wages. Consistent with this hypothesis, the article finds evidence using data on over 17,000 closed bodily injury claims that special damage claims that exceed their expected value receive proportionally lower general damage awards than claims that do not. Among the implications of this research is the possibility that insurers will be less zealous in challenging fraudulent special damage claims under a third‐party insurance regime than they will be under a first‐party insurance regime in which access to general damages is limited.
On the Consequences of Behavioral Adaptations in the Cost–Benefit Analysis of Road Safety Measures
Authors: Gossner Olivier , Picard Pierre
Published: November 2005

Abstract

It is sometimes argued that road safety measures or automobile safety standards fail to save lives because safer highways or safer cars induce more dangerous driving. A similar but less extreme view is that ignoring the behavioral adaptation of drivers would bias the cost–benefit analysis of a traffic safety measure. This article derives cost–benefit rules for automobile safety regulation when drivers may adapt their risk‐taking behavior in response to changes in the quality of the road network. The focus is on the financial externalities induced by accidents because of the insurance system as well as on the consequences of drivers' risk aversion. We establish that road safety measures are Pareto improving if their monetary cost is lower than the difference between their (adjusted for risk aversion) direct welfare gain with unchanged behavior and the induced variation in insured losses due to drivers' behavioral adaptation. The article also shows how this rule can be extended to take other accident external costs into account.
A Note on Bonus Scales
Authors: Andrade e Silva João Manuel , Centeno Maria de Lourdes
Published: November 2005

Abstract

We revisit the optimal bonus scales introduced by Norberg (Norberg, R., 1976, Scandinavian Actuarial Journal (2): 92‐107), Borgan, Hoem, and Norberg (Borgan, O., J. Hoem, and R. Norberg, 1981, Scandinavian Actuarial Journal (2): 165‐178), and Gilde and Sundt (Gilde, V., and B. Sundt, 1989, Scandinavian Actuarial Journal (1): 13‐22) and underline some potential problems of the linear scales. As a possible solution we propose the use of geometric scales.
Symptom dimensions in obsessive–compulsive disorder: prediction of cognitive‐behavior therapy outcome
Authors: Rufer M. , Fricke S. , Moritz S. , Kloss M. , Hand I.
Published: November 2005

Objective:  A significant number of patients with obsessive–compulsive disorder (OCD) fail to benefit sufficiently from treatments. This study aimed to evaluate whether certain OCD symptom dimensions were associated with cognitive‐behavioral therapy (CBT) outcome.

Method:  Symptoms of 104 CBT‐treated in‐patients with OCD were assessed with the clinician‐rated Yale‐Brown Obsessive–Compulsive Scale symptom checklist. Logistic regression analyses examined outcome predictors.

Results:  The most frequent OCD symptoms were aggressive and contamination obsessions, and compulsive checking and cleaning. Patients with hoarding symptoms at baseline (n = 19) were significantly less likely to become treatment responders as compared to patients without these symptoms. Patients with sexual and religious obsessions tended to respond less frequently, although this failed to reach statistical significance (P = 0.07). Regression analyses revealed that higher scores on the hoarding dimension were predictive of non‐response, even after controlling for possible confounding variables.

Conclusion:  Our results strongly indicate that in‐patients with obsessive–compulsive hoarding respond poorly to CBT.
The interaction between TPH2 promoter haplotypes and clinical–demographic risk factors in suicide victims with major psychoses
Authors: De Luca V. , Hlousek D. , Likhodi O. , Van Tol H. H. M. , Kennedy J. L. , Wong A. H. C.
Published: November 2005

Tryptophan hydroxylase isoform 2 (TPH2) is a rate‐limiting enzyme in the biosynthesis of serotonin (5‐HT) and is predominantly localized in the brain. Previous studies have suggested that there is an association between serotonergic dysfunction in the brain and suicidality. This study was designed to examine whether the −473T > A and −8396G > C polymorphisms of the TPH2 gene may be associated with completed suicide in subjects with major psychoses from the Stanley Foundation Brain Bank sample. TPH2 genotypes were determined in 69 subjects with a diagnosis of schizophrenia or bipolar disorder, among which 22 died by suicide. Genomic DNA was amplified by polymerase chain reaction and typed by automated methods. Both markers were found to be in Hardy–Weinberg equilibrium and in strong linkage disequilibrium. No association with history of suicide was found for either polymorphism. Haplotype analysis with ehap showed no association between completed suicide and haplotype distribution (χ2 = 1.877; 3 df; P = 0.598). Nor was there any association between suicide and these genetic markers even when clinical–demographic factors were considered as covariates in the haplotype analysis. These findings suggest that these 5′ marker haplotypes in the TPH2 gene do not influence suicidal behaviour.
Epidermale Stammzellen
Authors: Rzepka Karin , Schaarschmidt Grit , Nagler Michael , Wohlrab Johannes
Published: November 2005

Das moderne Verständnis der Biologie epidermaler Stammzellen eröffnet eine völlig neue Sichtweise der Funktion der Epidermis und angrenzender Epithelien. Aus dem Wissen um die Proliferation, Differenzierung und Regeneration von Keratinozyten ergeben sich eine Vielzahl pathogenetischer sowie klinisch‐therapeutischer Ansatzpunkte für verschiedenste Dermatosen.

Das Reservoir epidermaler Stammzellen findet sich in der interfollikulären Epidermis, der Haarbalgregion und der germinalen Haarfollikelmatrix. Hier existieren eigene Stammzellklone, die als Nachkommen transient amplifizierende und postmitotische Zellen bilden. Diese sind das zellbiologische Äquivalent des Stratum germinativum der Epidermis. Die Stammzellklone sind in Clustern organisiert und weisen eine hohe Expression von Adhäsionsproteinen auf, die ihre Stabilität in einer spezifischen Umgebung aus Subpopulationen von Gewebszellen und extrazellulären Substraten in der so genannten Stammzellnische sichern. Die Differenzierung wird durch eine regulatorische Kaskade chemischer Signale aus dem Umfeld der Stammzellen sowie dem Erbgut der Zelle bestimmt.

Die klinische Bedeutung von Stammzellen liegt vor allem in der Nutzung zur Therapie von Krankheiten, wobei durch Reimplantation autologer Stammzellen Epithelien rekonstruiert bzw. durch gezielte Transfektion gentherapeutische Ziele verfolgt werden können. Allerdings kann das Verhältnis von therapeutischem Nutzen zu den Risiken bisher nur begrenzt abgeschätzt werden.
Transglutaminases as diagnostically relevant autoantigens in patients with gluten sensitivity
Authors: Heil Peter Maximilian , Volc‐Platzer Beatrix , Karlhofer Franz , Gebhart Walter , Huber Wolf‐Dietrich , Benesch Thomas , Vogelsang Harald , Stingl Georg
Published: November 2005

Background: Patients with gluten sensitivity, i. e. celiac disease and dermatitis herpetiformis have anti‐endomysial antibodies recognizing transglutaminases, which are usually detected on appropriate tissue sections. It would be desirable to have available a reliable, tissue‐independent serological diagnostic tool. We compared disease‐specificity and sensitivity of tTG versus eTG‐based detection systems for the diagnosis of anti‐endomysial IgA‐antibodies.

Patients and Methods: We examined 204 serum samples in duplicates with commercial human ELISA‐kits: 54 healthy blood donors, 20 celiac disease, 29 dermatitis herpetiformis and 101 with other autoimmune dermatoses.

Results: The tTG‐based ELISA proved to be very disease‐specific (100 %) and sensitive for the diagnosis of gluten sensitivity (95 % celiac disease; 96.6 % dermatitis herpetiformis). The eTG‐based ELISA was also perfectly specific (100 %), but only 15 % of celiac disease‐sera and 44.8 % of dermatitis herpetiformis‐sera yielded positive results.

Conclusions: The human tTG‐ELISA fulfills all criteria of a screening test and, because of being investigator‐independent, inexpensive and highly reproducible, compares favorably with the current diagnostic gold standard (indirect immunofluorescence and biopsy) of celiac disease and dermatitis herpetiformis. The low sensitivity of the eTG‐ELISA may have technical reasons, but could theoretically also be linked to disease activity or indicate the existence of an as yet undefined disease subset. Studies are currently under way to address these issues.
Anogenitaldermatosen – allergische und irritative Auslösefaktoren Analyse von Daten des IVDK1 und Literaturübersicht
Authors: Kügler Katrin , Brinkmeier Thomas , Frosch Peter J. , Uter Wolfgang
Published: November 2005

Hintergrund: Anogenitaldermatosen (AGD) sind häufige und psychisch sehr belastende Erkrankungen. Klinisch ist oft unklar, ob eine Kontaktallergie oder irritative Faktoren beteiligt sind. Bezüglich Therapie und Prophylaxe ist von Bedeutung, welche Allergene oder Irritantien dann die Hauptrolle spielen.

Patienten und Methoden: Daten des Informationsverbundes Dermatologischer Kliniken (IVDK, Zentrale in Göttingen) von 1999 bis 2003 wurden ausgewertet. 1 168 Patienten mit der Hauptdiagnose AGD wurden bezüglich klinischer Parameter und der Ergebnisse der Epikutantestung mit dem Gesamtkollektiv verglichen. Die Reaktionsquoten wurden alters‐ und geschlechtsstandardisiert.

Ergebnisse: Der Verdacht auf ein allergisches Kontaktekzem bestand bei 39,5 % vor der Epikutantestung. Nach der Testung wurde bei 24,6 % die AGD als allergisches Kontaktekzem eingeordnet; eine chronisch irritative Dermatitis wurde bei 11,8 % diagnostiziert. Sonstige Diagnosen waren „Balanitis”, Lichen sclerosus et atrophicus sowie Herpes genitalis. Signifikant erhöhte Sensibilisierungsquoten gegenüber dem Kontrollkollektiv zeigten sich bei Patienten mit AGD für Cinchocain (6,6 %), Bufexamac (3,5 %) und Benzocain (2,4 %). Sofern irritative Faktoren eine Rolle als Ko‐Faktoren spielten (n = 422), wurden Feuchtigkeit (38,4 %), okklusives Milieu (30,3 %), mechanische Belastung (4,7 %) und Hitze (3,6 %) genannt.

Schlussfolgerung: Sensibilisierungen auf Cinchocain, Benzocain und Bufexamac kommen bei Patienten mit AGD häufiger vor als bei Patienten mit anderen Dermatosen. Daher sollten Medikamente mit diesen Wirkstoffen in der Praxis sehr zurückhaltend eingesetzt werden. Die Inhaltsstoffe von Wasch‐/Pflegemitteln sowie Kontrazeptiva verschiedenen Typs scheinen nach der Literatur insgesamt selten zu einer Kontaktallergie zu führen, obwohl kasuistische Mitteilungen vorhanden sind. Die ausführliche Testung mit der DKG‐Standardreihe, den oben genannten Hauptsensibilisatoren Cinchocain, Benzocain und Bufexamac, und insbesondere mit den vom Patienten verwendeten Pflege‐ und Hilfsmitteln wird empfohlen.
Polling Opinions in the 2005 Election
Authors: Baines Paul
Published: November 2005

The winners of the General Election in May were not the political parties but the opinion pollsters, says Paul Baines. After 1992, when most pollsters predicted a hung parliament rather than a Conservative win, and 2001, when they overestimated the Labour lead, the 2005 election result was awaited by many pollsters with trepidation. Would their final eve-of-poll results be accurate or not?
Meeting the Statistical Needs of 21st-Century Science
Authors: Mardia Kanti , Gilks Walter
Published: November 2005

Kanti Mardia and Walter Gilks consider the future role of statistics in scientific explanation and prediction, through views expressed by eminent scientists, philosophers and statisticians and through their own experience, particularly in the field of bioinformatics.
Do the Left-Handed Die Young?
Authors: Altman Doug , Bland Martin
Published: November 2005

Martin Bland and Doug Altman have been writing together for nearly 30 years, much of it about the consequences of misleading statistical analyses. In what they estimate to be their 79th publication, they comment on a long-running controversy: do left-handed people have shorter lives than the right-handed?
Career Story: Inside National Statistics
Authors: Dunnell Karen
Published: November 2005

Karen Dunnell has worked as a government statistician for most of her career, and when Len Cook resigned as National Statistician earlier this year she was appointed to take over from him. She tells Helen Joyce about her career and the challenges that lie ahead.
Structure And Uncertainty: Graphical Models for Understanding Complex Data
Authors: Best Nicky , Green Peter
Published: November 2005

Statistics is fundamental to making sense of the complexity of modern science. From the micro-level of the human genome to the macro-level of the universe, scientists need statistical models to help them extract meaning from empirical observations. Graphical models have been used across a wide variety of disciplines for building multivariate probabilistic models to represent, and draw inference about, complex phenomena. Nicky Best and Peter Green explain the ideas behind graphical models and show how they can be used to help tackle the challenges of complex statistical problems.
Exencephaly induction by valproic acid in the genetic polydactyly/arhinencephaly mouse,Pdn/Pdn
Authors: Maekawa Mizuho , Ohta Ken‐ichi , Katagiri Ryu‐ichi , Ueta Etsuko , Naruse Ichiro
Published: November 2005

ABSTRACT Non‐treated homozygous polydactyly/arhinencephaly (Pdn/Pdn) mouse fetuses exhibited exencephaly in 16.7% of cases. Treatment ofPdn/Pdnmice with 350 mg/kg of valproic acid (VPA) on days 8.5 and 9.5 of gestation increased the rate of exencephaly to 66.7%. The responsible gene for thePdnmouse phenotype has been determined to beGli3, and the suppression ofGli3gene expression has been documented inPdn/Pdnembryos. We investigated how the sonic hedgehog (Shh) andFgf8genes, the correlated genes ofGli3, are expressed in the VPA‐treated exencephalicPdn/Pdnembryos on day 10 of gestation, using whole mountin situhybridization (WISH) and real‐time PCR methods. We could not detect any alterations inShhexpression by real‐time PCR, or WISH in the non‐treatedPdn/Pdnand VPA‐treated exencephalicPdn/Pdnembryos. AlteredFgf8expression patterns were observed in the commissural plate and dorsal isthmal neuroepithelium in the non‐treatedPdn/Pdnembryos. We speculated that the altered expression ofFgf8might be the result of down‐regulation ofGli3inPdn/Pdnembryos.Fgf8gene expression in the commissural plate and dorsal isthmal neuroepithelium exhibits wide or altered signal patterns in the VPA‐treated exencephalicPdn/Pdnembryo. From these findings, it was suggested that down‐regulation ofGli3gene expression induced the altered expression ofFgf8in thePdn/Pdnembryos, and that VPA treatment accelerated the alterations ofFgf8gene expression in thePdn/Pdnembryos. It was further speculated that altered expression ofFgf8in the commissural plate may be the fundamental cause of exencephaly, and that the synergistic effect between gene and drug shown in this experiment may explain the differences of sensitivity in the side‐effects of the drug.
Comparative susceptibility of newborn and young rats to six industrial chemicals
Authors: Hasegawa Ryuichi , Hirata‐Koizumi Mutsuko , Takahashi Mika , Kamata Eiichi , Ema Makoto
Published: November 2005

ABSTRACT  To elucidate the comparative susceptibility of newborn rats to chemicals, newborn and young animals were administered six industrial chemicals by gavage from postnatal days (PND) 4 to 21, and for 28 days starting at 5–6 weeks of age respectively, under the same experimental conditions as far as possible. As two new toxicity endpoints specific to this comparative analysis, presumed no‐observed‐adverse‐effect‐levels (pNOAELs) were estimated based on results of both main and dose‐finding studies, and presumed unequivocally toxic levels (pUETLs) were also decided. pNOAELs for newborn and young rats were 40 and 200 for 2‐chlorophenol, 100 and 100 for 4‐chlorophenol, 30 and 100 for p‐(α,α‐dimethylbenzyl) phenol, 100 and 40 for (hydroxyphenyl)methyl phenol, 60 and 12 for trityl chloride, and 100 and 300 mg/kg/day for 1,3,5‐trihydroxybenezene, respectively. To determine pUETLs, dose ranges were adopted in several cases because of the limited results of experimental doses. Values for newborn and young rats were thus estimated as 200–250 and 1000 for 2‐chlorophenol, 300 and 500 for 4‐chlorophenol, 300 and 700–800 for p‐(α,α‐dimethylbenzyl) phenol, 140–160 and 1000 for (hydroxyphenyl)methyl phenol, 400–500 and 300 for trityl chloride, and 500 and 1000 mg/kg/day for 1,3,5‐trihydroxybenzene, respectively. In most cases, newborn rats were 2–5 times more susceptible than young rats in terms of both the pNOAEL and the pUETL. An exception was that young rats were clearly more susceptible than their newborn counterparts for trityl chloride.
Spontaneous regression of congenital cystic adenomatoid malformation of the lung: Longitudinal examinations by magnetic resonance imaging
Authors: Kawamura Makoto , Itoh Hiroaki , Yamada Shigehito , Yura Shigeo , Katsuya Satoko , Kosaka Kenzo , Tatsumi Keiji , Hamanishi Junzo , Suzuki Ayako , Fujii Shingo
Published: November 2005

ABSTRACT  We report a case of large cystic adenomatoid malformation of the lung (CCAM), which occupied almost the entire left lung with a prominent mediastinal shift at 24 weeks of gestation. The volume of the lesion, determined by magnetic resonance imaging (MRI), was 27.0 cm3. Subsequent MRI and ultrasound examinations revealed a spontaneous resolution of the lesion at 32 and 36 weeks of gestation without a mediastinal shift, when the lesion volume was 12.8 cm3 and 5.6 cm3, respectively. At 37 weeks of gestation, a mature male baby weighing 2638 g with an Apgar score of 7 was delivered by elective cesarean section. A lobectomy of the left upper lobe of the lung was carried out at 3 days of age, due to an enlargement of the CCAM after birth.
AT1 receptors are necessary for eccentric training‐induced hypertrophy and strength gains in rat skeletal muscle
Authors: McBride Todd A.
Published: November 2005

This study was undertaken to measure the response of skeletal muscle to eccentric contractions (EC) in the presence of the angiotensin type 1 (AT1) receptor blocker, losartan. It was hypothesized that blocking AT1 receptors prior to an initial bout of EC would prevent the muscle from developing the normal adaptation to EC as demonstrated by the repeated bout effect. It was also hypothesized that continuous AT1 receptor blockade during EC training would significantly reduce muscle hypertrophy and strength gains that occur with repeated EC. Rats received losartan in their drinking water at either a low dose (20 mg (kg body weight)−1 day−1) or a high dose (40 mg (kg body weight)−1 day−1). Each bout of EC consisted of a total of 24 contractions. Rats were assigned to four groups: a single acute bout of EC (n= 6); two bouts of EC separated by 14 days (n= 8); and 4 weeks of training twice a week on the low dose (n= 5) or the high dose (n= 9). There was no effect of AT1 receptor blockade on the initial loss of function following a single acute bout of EC, or on the repeated bout effect following a second exposure to EC. AT1 receptor blockade did alter the results of EC training, in both the low and high dose groups. Losartan treatments prevented EC training‐induced increases in muscle wet and dry weights compared to untreated rats. Finally, the low and high dose losartan treatments also prevented an increase in muscle contractile force following EC training compared to the untreated group. Functional AT1 receptors are therefore not necessary for an acute adaptation to EC as demonstrated by the repeated bout effect, but are necessary for muscle hypertrophy and increased contractile force associated with EC training.
Estimation of Resonance Energy from Forced Nonplanar Conformations of Conjugated Molecules
Authors: Böhm Stanislav , Exner Otto
Published: November 2005

Energies of 39 derivatives of buta-1,3-diene in the twisted conformation were calculated within the framework of the density functional theory at the B3LYP/6-311+G(d,p) level. By comparing with the same molecules in their natural minimum-energy conformations, a scale of resonance effects of various substituents was obtained and expressed in terms of isodesmic reactions. Comparison with other similar scales revealed that this model is not particularly advantageous, its main shortcoming being the relatively small effect. In any case it confirmed that the scales of resonance effects obtained from different models are only very roughly proportional: the classical model of resonance works well in representative examples but has its clear limitation when unduly extended.
Syntheses and 1H, 13C, 15N, 17O, 205Tl NMR of New Ring-Functionalised Chelating Half-Sandwich Complexes of Thallium(I) Containing an N-, O- or S-Donor Atom
Authors: Tromp Dorette S. , Frühauf Hans-Werner , Elsevier Cornelis J.
Published: November 2005

Novel, ring-functionalised cyclopentadienylthallium(I) complexes have been synthesised in good to moderate yields from thallium ethoxide and N-, O- and S-alkyl substituted cyclopentadienes in diethyl ether at 0 °C. The new compounds have been analysed by 1H, 13C, 15N, 17O and 205Tl NMR, which revealed that cyclopentadienyl ring and the donor atom in the side chain are coordinated to thallium; they are mononuclear complexes. Hence, these compounds can be viewed as analogues of their parent, CpTl, but their solubility is much enhanced because of the mononuclear nature due to the presence of the side chain. The thallium(I) complexes with the (dimethylamino)ethyl, methoxyethyl and (methylsulfanyl)ethyl side chain are promising reagents for transmetallation reactions.
A Synthesis of the C1-C9 Fragment of Ionomycin Using Cationic η3-Allylicmolybdenum and -Iron Complexes
Authors: Cooksey John , Kocienski Philip , Li Ying-Fa
Published: November 2005

A key step in the synthesis of the C1-C9 fragment of the ionophore antibiotic ionomycin involves the addition of an alkylcopper(I) reagent to an ester-functionalised cationic η3-allylicmolybdenum and an alkylzinc cuprate to the corresponding η3-allyliciron complex. The reaction is regioselective and the metal directs enantiofacial attack (anti). The stereochemistry of the reactions is proven by an independent synthesis.
Informed consent and participant perceptions of influenza vaccine trials in South Africa
Authors: Moodley K , Pather M , Myer L
Published: November 2005

Background and objectives:There are few insights from sub-Saharan Africa on research participants’ experiences of the informed consent process, particularly in the context of randomised controlled trials, where issues of randomisation and the use of placebos may be confusing concepts for participants. This study investigated the knowledge and perceptions of the informed consent process among individuals participating in influenza vaccine trials in two disadvantaged communities in South Africa.

Method:Four to 12 months after completion of the trials, participants were contacted to return to participate in the informed consent study. The semistructured questionnaire administered to assess recall of trial procedures and the informed consent process covered key issues including: purpose of the study; awareness that the study was not part of routine treatment; voluntary nature of participation and freedom to withdraw; randomisation; placebos; and remuneration.

Results:A total of 334 participants (93% of the original vaccine trial sample; mean age 68 years, median level of education grade 8, 69% women) completed the questionnaire. Only 21% were able to recall that they were allocated randomly to the different treatment arms. Only 19% of those involved in the placebo controlled study had interpreted the concept of placebo as an inactive medication.

Conclusion:Although a good general recall of trial concepts was demonstrated, only a small proportion of the participants correctly interpreted and recalled the concepts of randomisation and placebos. Informed consent in this and similarly disadvantaged communities may often be inadequate and new ways to improve understanding of the research process should be explored.