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Biomedical subjects

Andreas Becker

Publications and source records attributed to Andreas Becker.

At least 19 recordsLinked to original sources

Psychopathological profile in children with chronic tic disorder and co-existing ADHD: additive effects.

The nature of the co-occurrence of chronic tic disorders (CTD) and attention deficit hyperactivity disorder (ADHD) is unclear. Especially in the field of psychopathology, the relationship of CTD and ADHD remains to be clarified. Thus, the aim of the present chart review study was to specify the contribution of CTD and/or ADHD to the psychopathological profile of the comorbid group (CTD+ADHD). The psychopathological profiles of four large groups (CTD-only (n=112), CTD+ADHD (n=82), ADHD-only (n=129), controls (n=144)) were measured by the eight subscales of the Child Behavior Checklist (CBCL) and analyzed by a 2x2 factorial design followed by contrasts. There were main effects of ADHD diagnosis on all but one subscale of the CBCL (Somatic Complaints). For CTD diagnosis, main effects were found for Attention Problems, Anxious/Depressed, Thought Problems, Social Problems and Somatic Complaints. The only interaction effect was seen for Somatic Complaints. While CTD and ADHD were both related to internalizing psychopathology of children in the CTD+ADHD group, ADHD had the largest effect on externalizing psychopathology in the comorbid group. At the level of psychopathology, an additive model for the co-occurrence of CTD and ADHD is strongly supported. In the comorbid group (CTD+ADHD), the ADHD diagnosis shows the strongest relation to externalizing psychopathology.

Aggression↗

Plasma density inside a femtosecond laser filament in air: strong dependence on external focusing.

Our experiment shows that external focusing strongly influences the plasma density and the diameter of femtosecond Ti-sapphire laser filaments generated in air. The control of plasma filament parameters is suitable for many applications such as remote spectroscopy, laser induced electrical discharge, and femtosecond laser material interactions. The measurements of the filament showed the plasma density increases from 10(15)cm(-3) to 2 x 10(18)cm(-3) when the focal length decreases from 380 cm to 10 cm while the diameter of the plasma column varies from 30 microm to 90 microm. The experimental results are in good qualitative agreement with the results of numerical simulations.

Journal Article↗

Tunable ultrashort laser pulses generated through filamentation in gases.

Tunable and stable ultrashort laser pulses in the visible spectrum are generated with high efficiency by four-wave mixing process during the filamentation of near-infrared and infrared laser pulses in gases. It is shown that these tunable ultrashort pulses have a very low energy fluctuation and an excellent mode quality due to the processes of intensity clamping and self-filtering in the filament.

Journal Article↗

Decreased serum semicarbazide sensitive aminooxidase (SSAO) activity in patients with major depression.

Semicarbazide sensitive aminooxidase (SSAO) is known to interplay with monoamine oxidases (MAO) and several antidepressants. Taking into account the monoamine hypothesis concerning the pathophysiology of depression, the aim of the present pilot study was to evaluate serum SSAO activity in depressed patients. A total of 21 inpatients with major depression and 41 healthy controls were studied. Serum SSAO activity was determined by HPLC on days 1, 5 and 10 of inpatient treatment. At baseline without medication including antidepressants, highly depressed patients (MADRS score>or=30) had significantly decreased serum SSAO activity (mean 385+/-161 mU/l) when compared to healthy controls (mean 526+/-141 mU/l; p=0.003). This SSAO decrease was less pronounced at day 5 and day 10 under an antidepressive drug regime. Decreased serum SSAO activity was observed in patients with major depression, especially in those with high MADRS scores. The present results support the hypothesis of dysfunctional monoaminergic metabolism in the pathogenesis of depressive disorders. The disputable association between depression and monoamine metabolism requires further investigation, particularly with regard to SSAO activity and medication status.

Amine Oxidase (Copper-Containing)↗

Ab initio calculation of the double ionization of helium in a few-cycle laser pulse beyond the one-dimensional approximation.

We present ab initio computations of the ionization of two-electron atoms by short pulses of intense linearly polarized Ti:sapphire laser radiation beyond the one-dimensional approximation. In the model the electron correlation is included in its full dimensionality, while the center-of-mass motion is restricted along the polarization axis. Our results exhibit a rich double ionization quantum dynamics in the direction transversal to the field polarization, which is neglected in the previous models based on the one-dimensional approximation.

Journal Article↗

Serum level of semicarbazide-sensitive amine oxidase in children with ADHD.

BACKGROUND: The objective of this study was to analyze the extracellularly acting semicarbazide-sensitive amine oxidase (SSAO) serum levels in children with ADHD for the first time. SSAO is known to show deviations from normal in various somatic disorders and to interplay with the intracellularly active MAO. In humans two forms of SSAO a circulating form in plasma and a membrane-bound form are involved in monoaminergic metabolism. METHODS: We analyzed serum levels of SSAO in 27 children meeting ICD-10 criteria of Hyperkinetic Disorder (F90) or DSM-IV criteria of ADHD combined type by HPLC method and fluorimetric detection. A group of 42 healthy volunteers within the same age range (7.0 - 14.0 years) served as controls. RESULTS: No significant differences between children with ADHD (SSAO activity M = 773, SD = 217 mU/l) and healthy controls (SSAO activity M = 775, SD = 256 mU/l) in SSAO serum levels were found (F = 2.18; p > 0.14). Further, stimulant medication status had no influence on the result (F = 2.52; p > 0.11). CONCLUSION: There is no evidence for a deviation of SSAO serum activity in ADHD. Hence, extracellularly acting SSAO does not seem to be a promising factor for further research in ADHD. But progress in knowledge of its physiologic role and of the relationship between the membrane-bound and the circulating serum form may open new avenues for research on SSAO in ADHD.

Journal Article↗

Daily monitoring of nucleated red blood cells in the blood of surgical intensive care patients.

BACKGROUND: In intensive care patients the appearance of nucleated red blood cells (NRBC) in blood is associated with a variety of severe diseases. Generally, when NRBCs are detected in the patients' blood the prognosis is poor. MATERIAL AND METHODS: In the present study the detection of NRBCs was used for a day-to-day monitoring of 284 surgical intensive care patients. RESULTS: NRBCs were found at least once in 32.0% of all patients. The mortality of NRBC-positive patients was 44.0% (40/91); this was significantly higher (P<0.001) than the mortality of NRBC-negative patients (4.2%, 8/193). With regard to intensive care mortality, NRBCs in blood showed sensitivity and specificity of 83.3% and 78.9%, respectively. The area under curve (C-statistic) was 0.86. Mortality increased with increasing NRBC concentration. All patients with more than 2000 NRBCs/microl died. Moreover, mortality increased with increasing frequency of occurrence. When after first detection of NRBCs in blood, during the further course of intensive care treatment the NRBCs have disappeared from the circulation, the mortality again decreased to values of NRBC-negative patients. The detection of NRBCs is associated with an increased mortality rate, the odds ratio after adjustment for other laboratory prognostic indicators being 1.8 (P<0.001) for each increase in the NRBC category (1-40/microl; 41-80/microl; 81-240/microl, >240/microl). NRBCs were detected for the first time, on average, 9 days (median 5 days) before death. CONCLUSIONS: The routine analysis of NRBC in blood is of potential prognostic power with regard to mortality of critically ill patients. Therefore, this parameter could possibly serve as a daily indicator of patients at high mortality risk.

Adolescent↗

Psychopathological screening of children with ADHD: Strengths and Difficulties Questionnaire in a pan-European study.

OBJECTIVE: To examine the psychometric properties of the Strengths and Difficulties Questionnaire (SDQ) parent version and to determine the effects of age, gender, country and investigator type (paediatrician, child psychiatrist, other physician) on the SDQ scores in the prospective, non-interventional ADORE study. METHODS: The SDQ was completed for 1,459 children with ADHD (aged 6-18 years) in 10 European countries. RESULTS: Factor analysis provided an exact replication of the original 5-factor SDQ subscale structure. All subscales were sufficiently homogeneous. The mean total difficulties and SDQ subscale scores of the ADORE sample clearly differed from UK normative data. Younger children were more impaired on different SDQ scales than older children, and girls were more emotionally affected than boys. Differences between countries were found for each SDQ scale, but the investigator type had no significant effect. Correlation coefficients between SDQ scales and other scales used in ADORE ranged from low (r<0.30) to high (r>0.50). CONCLUSIONS: The present study confirmed the validity and reliability of the parent-reported SDQ scale structure and showed that the scale scores are dependent on age and gender. In contrast to investigator type, different cultures had a significant effect on SDQ scores. Correlations with other scales used in the ADORE study underline both separate domains and meaningful associations.

Adolescent↗

Colour perception in ADHD.

Attention-deficit/hyperactivity disorder (ADHD) is associated with unexplained impairments on speeded naming of coloured stimuli. These deficits may reflect hypofunctioning retinal dopaminergic mechanisms impairing particularly blue-yellow colour discrimination. Colour perception and rapid colour naming ability were investigated in 14 children with ADHD and 13 healthy peers matched for age, gender, and IQ, using the Farnsworth-Munsell 100 Hue Test (FMT) and the Stroop-Colour-Word test. Children with ADHD committed more errors on the FMT, particularly on discrimination of colours along the blue-yellow axis, and were slower on Stroop subtests involving colour naming. However, the latter deficit was accounted for similarly by blue-yellow and red-green discrimination abilities. Blue-yellow colour perception problems in ADHD contribute to but do not fully explain the observed slowed colour naming.

Adolescent↗

Poor prognosis indicated by nucleated red blood cells in peripheral blood is not associated with organ failure of the liver or kidney.

BACKGROUND: The appearance of nucleated red blood cells (NRBCs) in peripheral blood is associated with a variety of severe diseases. When NRBCs are detected in blood, this is generally associated with increased mortality. METHODS: In a prospective study, NRBCs and other laboratory parameters were measured daily in the peripheral blood of surgical intensive care patients. The appearance of NRBCs was analyzed in relation to laboratory indicators of organ injury. RESULTS: A total of 284 surgical intensive care patients were included in this study. The mortality of NRBC-positive patients was 44.0% (40/91). This was significantly higher (p<0.001) than the mortality of NRBC-negative patients (4.2%, 8/193). Mortality increased with the NRBC concentration and the length of the NRBC-positive period. Multiple logistic regression analysis of several other clinical and laboratory risk indicators revealed a significant association between NRBCs and increased mortality, with an odds ratio of 1.95 (95% CI 1.35-2.82; p<0.001) for each increment in NRBC category (0, 1-40, 41-80, 81-240 and >240 NRBC/microL). After the initial detection of NRBCs in blood, there were no significant increases in creatinine concentrations or alanine aminotransferase activity. However, the appearance of NRBCs coincided with increasing C-reactive protein and thrombocyte concentrations. CONCLUSIONS: The detection of NRBCs in blood of surgical intensive care patients is of prognostic power with regard to patient mortality. This prognostic significance of NRBCs was independent of some clinical and other laboratory risk parameters. The appearance of NRBCs in blood was not associated with kidney failure or lesion of the liver.

Adolescent↗

Molecular basis for the glyphosate-insensitivity of the reaction of 5-enolpyruvylshikimate 3-phosphate synthase with shikimate.

The shikimate pathway enzyme 5-enolpyruvyl shikimate-3-phosphate synthase (EPSP synthase) has received attention in the past because it is the target of the broad-spectrum herbicide glyphosate. The natural substrate of EPSP synthase is shikimate-3-phosphate. However, this enzyme can also utilize shikimate as substrate. Remarkably, this reaction is insensitive to inhibition by glyphosate. Crystallographic analysis of EPSP synthase from Escherichia coli, in complex with shikimate/glyphosate at 1.5 Angstroms resolution, revealed that binding of shikimate induces changes around the backbone of the active site, which in turn impact the efficient binding of glyphosate. The implications from these findings with respect to the design of novel glyphosate-insensitive EPSP synthase enzymes are discussed.

3-Phosphoshikimate 1-Carboxyvinyltransferase↗

Crystal structure of the GTPase domain of rat dynamin 1.

Here, we present the 1.9-A crystal structure of the nucleotide-free GTPase domain of dynamin 1 from Rattus norvegicus. The structure corresponds to an extended form of the canonical GTPase fold observed in Ras proteins. Both nucleotide-binding switch motifs are well resolved, adopting conformations that closely resemble a GTP-bound state not previously observed for nucleotide-free GTPases. Two highly conserved arginines, Arg-66 and Arg-67, greatly restrict the mobility of switch I and are ideally positioned to relay information about the nucleotide state to other parts of the protein. Our results support a model in which switch I residue Arg-59 gates GTP binding in an assembly-dependent manner and the GTPase effector domain functions as an assembly-dependent GTPase activating protein in the fashion of RGS-type GAPs.

Animals↗

Interaction of phosphonate analogues of the tetrahedral reaction intermediate with 5-enolpyruvylshikimate-3-phosphate synthase in atomic detail.

The enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) catalyzes the penultimate step of the shikimate pathway and is the target of the broad-spectrum herbicide glyphosate. Since the functionality of the shikimate pathway is vital not only for plants but also for microorganisms, EPSPS is considered a prospective target for the development of novel antibiotics. We have kinetically analyzed and determined the crystal structures of Escherichia coli EPSPS inhibited by (R)- and (S)-configured phosphonate analogues of the tetrahedral reaction intermediate. Both diastereomers are competitive inhibitors with respect to the substrates of the EPSPS reaction, shikimate-3-phosphate (S3P) and phosphoenolpyruvate (PEP). Remarkably, the (S)-phosphonate (K(iS3P) = 750 nM), whose configuration corresponds to that of the genuine tetrahedral intermediate, is a much weaker inhibitor than the (R)-phosphonate analogue (K(iS3P) = 16 nM). The crystal structures of EPSPS liganded with the (S)- and (R)-phosphonates, at 1.5 and 1.9 A resolution, respectively, revealed that binding of the (R)-phosphonate induces conformational changes of the strictly conserved residues Arg124 and Glu341 within the active site. This appears to give rise to substantial structural alterations in the amino-terminal globular domain of the enzyme. By contrast, binding of the (S)-phosphonate renders the enzyme structure unchanged. Thus, EPSPS may facilitate the tight binding of structurally diverse ligands through conformational flexibility. Molecular docking calculations did not explain why the (R)-phosphonate is the better inhibitor. Therefore, we propose that the structural events during the open-closed transition of EPSPS are altered as a result of inhibitor action.

3-Phosphoshikimate 1-Carboxyvinyltransferase↗

Neuronal network models of ADHD -- lateralization with respect to interhemispheric connectivity reconsidered.

BACKGROUND: Recent research on structural and functional anatomy related to ADHD has concentrated on fronto-striatocerebellar circuits. These findings and resultant neurobiological models of ADHD may explain some of the disturbances. On the other hand, there is some evidence that the restricted look at anterior-posterior anomalies might neglect the important additional information of lateralization problems related to hemispheric connectivity. OBJECTIVE: Hence, the role of lateralization in the pathophysiology of ADHD should be reconsidered. METHOD: After a short review of imaging studies in ADHD the special role of the corpus callosum (including the influence of its anomalies on general brain development, lateralization and functioning) is outlined and the first case of total agenesis of corpus callosum in a child with ADHD is presented and discussed within this context. CONCLUSIONS: In view of the remaining inconsistencies concerning structural and functional brain anomalies in ADHD, attention should be paid not only to anterior- posterior but also to left-right aspects of functional and structural brain anomalies. This should include disturbances probably related to anomalies of the corpus callosum, especially in regard to co-existing problems like dyslexia and developmental coordination disorder.

Agenesis of Corpus Callosum↗

Normative data and scale properties of the German parent SDQ.

BACKGROUND AND OBJECTIVES: The Strengths and Difficulties Questionnaire (SDQ) is a short assessment instrument which addresses positive and negative behavioural attributes of children and adolescents and generates scores for clinically relevant aspects. Although this brief questionnaire has been widely used in Germany to gather information from parents, teachers, and older children themselves, normative results obtained with the German version have not yet been reported to the international scientific community. To allow comparisons with SDQ findings in other countries, normative data for the German parent-rated form as well as a community-based evaluation of scale properties are summarised and complemented by results obtained in a number of clinical samples. METHODS: Parent ratings were collected for a community-based sample of 930 children and adolescents aged between 6 and 16 years, in which both genders and all age levels were equally represented. Statistical evaluation of psychometric properties included a factor analysis verifying the proposed scale structure, assessment of scale homogeneities, and determination of age, gender and social class effects. Based on the distributions of SDQ scores observed in this normative sample, recommended bandings identifying normal, borderline, and clinical ranges were defined for each scale. RESULTS: Exact replication of the original scale structure, satisfactory internal reliabilities, and observation of the expected associations with age and gender confirmed the equivalence of the German SDQ parent questionnaire with the English original. Differences between community-based results and clinical groups provided descriptive evidence of a dramatic impact of clinically defined psychiatric status on SDQ scores. CONCLUSIONS: After evaluating parent ratings obtained in a community-based sample, the German SDQ was shown to possess favourable psychometric properties. Thus, the German translation of this popular and versatile instrument seems to be a similarly reliable and useful assessment tool as the original English questionnaire.

Adolescent↗

Validation of the parent and teacher SDQ in a clinical sample.

OBJECTIVES: This study examines whether the German translation of the Strengths and Difficulties Questionnaire (SDQ) is a reliable and valid screening instrument and whether it is as effective a tool for clinical diagnostics and scientific applications as the CBCL/TRF. METHODS: We examined 543 children and adolescents (147 girls and 396 boys) with ages ranging from 5 to 17 years and correlated the results of the parent and teacher SDQ as well as the CBCL/TRF with clinical diagnoses. Furthermore, the adequacy of the scale structure of the SDQ was tested using confirmatory and exploratory factor analyses. RESULTS: It was demonstrated that the scales of the parent and teacher versions were sufficiently homogeneous (0.72-0.83). Correlations between SDQ scales and corresponding CBCL/TRF scales showed a high degree of congruence, while an exact replication of the original SDQ scale structure could also be achieved. Parent and teacher versions of both questionnaires presented with good validity, not only with regard to the discrimination between child psychiatric patients and a representative community sample, but also in the identification of different categories of disorders within the clinical sample. CONCLUSION: The parent and teacher SDQs proved to be valid and helpful questionnaires for use in the framework of a multi-dimensional behavioural assessment, and appear to be well suited for screening purposes, longitudinal monitoring of therapeutic effects, and scientific research purposes.

Adolescent↗

Evaluation of the self-reported SDQ in a clinical setting: do self-reports tell us more than ratings by adult informants?

OBJECTIVES: The aim of this study was to evaluate the German self-reported Strengths and Difficulties Questionnaire (SDQ) in a clinical setting. We also investigated whether this additional information gathered directly from older children and adolescents improves the prediction of clinical status when external ratings from their parents and/or teachers are already available. METHODS: SDQ self-reports were collected from 214 in- and outpatients (81 girls and 133 boys) aged 11 to 17 years who were seen at the department of child and adolescent psychiatry of the University of Göttingen. Results obtained with the self-rated questionnaire were compared with the parent and teacher SDQs, corresponding CBCL/YSR scores, and the clinical diagnostic classification. Finally, the additional diagnostic benefits of the self-reports were examined. RESULTS: The scales of the SDQ self-report proved to be sufficiently homogeneous, and acceptable correlations were found with the equivalent parent and teacher ratings. The self-rated version of the SDQ demonstrated good validity with respect to the differentiation between clinically defined cases and non-cases and in detecting various subcategories of psychiatric disorders within the clinic sample. SDQ self-reports significantly contributed to the prediction of diagnostic status, specifically if only parent or teacher ratings were available. CONCLUSIONS: The self-rated version of the SDQ was shown to be a reliable and valid method for the assessment of behavioural problems in children and adolescents. In the absence of adult informant reports from parents and teachers, the diagnostic value of self-ratings was also demonstrated.

Adolescent↗

Autosomal dominant congenital nystagmus is not linked to 6p12, 7p11, and 15q11 in a German family.

PURPOSE: Congenital nystagmus (CN) is an eye-movement disorder that usually starts within the first months of life. Autosomal dominant, autosomal recessive, and X-chromosomal pedigree patterns are observed. Causative genes are yet unknown. Several loci were implicated to contain disease-relevant genes for autosomal dominant CN (AD CN). AD CN cosegregated with a balanced translocation of 7;15 in a family. In a large black pedigree linkage was demonstrated to 6p12. DESIGN: In this study, we describe a large German family with AD congenital nystagmus. Linkage of AD in this family was tested with previously implicated loci. METHODS: Affected family members and unaffected members underwent genetic analysis. Key family members underwent ophthalmologic testing and oculography. RESULTS: No linkage of AD CN to the implicated loci on 6p12, and 7p11, and 15q11 was found in this study. CONCLUSION: In the presented pedigree genes on 15q11, and on the assumption of full penetrance, 6p12 and 7p11 are not involved in the development of AD congenital nystagmus.

Chromosomes, Human, Pair 15↗