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Biomedical subjects

M Bartels

Publications and source records attributed to M Bartels.

At least 19 recordsLinked to original sources
PubMed2005

Diminished production of proinflammatory cytokines in patients with Alzheimer's disease.

Cerebral inflammation as well as systemic immunological alterations have been reported in Alzheimer's disease (AD). We examined the production of the proinflammatory cytokines interleukin-6, interleukin-12, interferon-gamma, and tumor necrosis factor-alpha in whole blood cell cultures of AD patients and age-matched controls. The production of all measured cytokines after mitogen stimulation is significantly decreased in the AD group compared to controls. The results reflect an attenuated secretory activity of monocytes/macrophages, but also of T-helper cells. The data sustain the assumption that a systemic, possibly age-related alteration of immune mechanisms may play a pathogenetic role in the development of AD.

Aged↗
PubMed2005

Changes in quality of life after renal transplantation.

Quality of life is becoming an increasingly important concept in the evaluation of different therapeutic interventions. In this cross-sectional study, quality of life analyzed in 76 renal transplant patients was compared with 65 patients with end-stage renal disease (ESRD) awaiting transplantation. Both groups were asked to estimate their subjective quality of life by responding to a multidimensional questionnaire that sought information in the following areas: (1) sociodemographic data, (2) a personality test (Giessen-Test), (3) information about employment, (4) assessment of anxiety and depression (GHQ-28), (5) the SF-36 as an important measurement for quality of life, and (6) the ESRD symptom checklist-transplantation module. The sociodemographic profiles of both groups were similar. The SF-36 revealed significantly higher values for transplant recipients in terms of physical functioning (P < or = .001), general health perceptions (P < or = .01), social functioning (P < or = .01), and physical summary value (P < or = .001). The other tests (Giessen-Test and GHQ-28) and employment data showed no significant differences between the two samples. Collectively, the data demonstrate a considerable improvement in quality of life in renal transplant patients. Despite good physical recovery and higher quality of life after transplantation, the rate of vocational rehabilitation remained low, partially explained by the currently high levels of unemployment.

Affect↗
PubMed2005

Computerized CT-based 3D visualization technique in living related liver transplantation.

INTRODUCTION: For living donor liver transplantation (LDLT) accurate diagnostic workup is essential. Multiple imaging approaches are currently used. Problems arise in the assessment of vascular and bile duct anatomy, liver graft volume, and vascular territories involved. A 3D visualization system that improves anatomic assessment, allows interactive surgery planning, and acts as an intraoperative guide with enhanced precision is required. Refinements in computed tomography (CT) technology with the introduction of multidetector-row CT scanners and implementation of mathematical methods on computerized digital data has enabled CT-based 3D visualizations. MATERIALS AND METHODS: Sixteen LDLT candidates and three LDLT recipients were assessed by multislice CT examination. Image processing of the digital raw data for 3D visualization included segmentation and calculation of center lines. A hierarchical mathematical model representing the vascular and biliary tree was created. This allowed calculation of individual vascular territories. RESULTS: 3D CT-based visualization in LDLT facilitates diagnostic workup with high accuracy for analyses of vascular and bile duct variants, volumetry, and assessment of the optimal surgical splitting line of the living donor liver. Resultant areas of either arterial devascularization or venous congestion can be displayed and quantified preoperatively. The diagnostic method is of major impact on patient selection and directly influences intraoperative surgical guidance. The currently practiced "multiple imaging approach" approach, especially with regard to invasive diagnostics, can be avoided in the future.

Family↗
PubMed2004

A multi-laboratory evaluation of a common in vitro pepsin digestion assay protocol used in assessing the safety of novel proteins.

Rationale. Evaluation of the potential allergenicity of proteins derived from genetically modified foods has involved a weight of evidence approach that incorporates an evaluation of protein digestibility in pepsin. Currently, there is no standardized protocol to assess the digestibility of proteins using simulated gastric fluid. Potential variations in assay parameters include: pH, pepsin purity, pepsin to target protein ratio, target protein purity, and method of detection. The objective was to assess the digestibility of a common set of proteins in nine independent laboratories to determine the reproducibility of the assay when performed using a common protocol. Methods. A single lot of each test protein and pepsin was obtained and distributed to each laboratory. The test proteins consisted of Ara h 2 (a peanut conglutin-like protein), beta-lactoglobulin, bovine serum albumin, concanavalin A, horseradish peroxidase, ovalbumin, ovomucoid, phosphinothricin acetyltransferase, ribulose diphosphate carboxylase, and soybean trypsin inhibitor. A ratio of 10U of pepsin activity/microg test protein was selected for all tests (3:1 pepsin to protein, w:w). Digestions were performed at pH 1.2 and 2.0, with sampling at 0.5, 2, 5, 10, 20, 30, and 60min. Protein digestibility was assessed from stained gels following SDS-PAGE of digestion samples and controls. Results. Results were relatively consistent across laboratories for the full-length proteins. The identification of proteolytic fragments was less consistent, being affected by different fixation and staining methods. Overall, assay pH did not influence the time to disappearance of the full-length protein or protein fragments, however, results across laboratories were more consistent at pH 1.2 (91% agreement) than pH 2.0 (77%). Conclusions. These data demonstrate that this common protocol for evaluating the in vitro digestibility of proteins is reproducible and yields consistent results when performed using the same proteins at different laboratories.

Clinical Laboratory Techniques↗
PubMed2004

Genetic and environmental mechanisms underlying stability and change in problem behaviors at ages 3, 7, 10, and 12.

Maternal ratings on internalizing (INT) and externalizing (EXT) behaviors were collected in a large, population-based longitudinal sample. The numbers of participating twin pairs at ages 3, 7, 10, and 12 were 5,602, 5,115, 2,956, and 1,481, respectively. Stability in both behaviors was accounted for by genetic and shared environmental influences. The genetic contribution to stability (INT: 43%; EXT: 60%) resulted from the fact that a subset of genes expressed at an earlier age was still active at the next time point. A common set of shared environmental factors operated at all ages (INT: 47%; EXT: 34%). The modest contribution of nonshared environmental factors (INT: 10%; EXT: 6%) could not be captured by a simple model. Significant age-specific influences were found for all components, indicating that genetic and environmental factors also contributed to changes in problem behavior.

Adolescent↗
PubMed2004

Heritability of attention problems in children: longitudinal results from a study of twins, age 3 to 12.

BACKGROUND: Twin studies of childhood behavior problems support the conclusion that individual differences in impulsivity, hyperactivity, and inattention are largely due to genetic influences. Non-genetic variation is due to environmental influences that are unique to the individual, and possibly to rater contrast effects. In the present longitudinal twin study, we report on the size of genetic and environmental effects on individual differences in attention problems at ages 3, 7, 10 and 12 years. METHODS: Mothers were asked to complete the CBCL for their twin offspring when the children were 3 (n = 11,938), 7 (n = 10,657), 10 (n = 6,192), and 12 years old (n = 3,124). We focus on the Overactivity (OA) scale in the Child Behavior Checklist (CBCL/2-3), and on the Attention Problem (AP) scale of the CBCL/4-18. The data were analyzed using longitudinal structural equation modeling. RESULTS: Broad heritability of OA and AP is estimated at nearly 75%, at each age. A contrast effect was observed at age 3 only. The results revealed less stability of OA at age 3 to AP at age 7 (r = .40), compared to the stability from AP at age 7 and beyond (r = .70). Genetic effects explained between 76% and 92% of the covariance between OA and AP. CONCLUSIONS: OA and AP are highly heritable at all ages in both genders. The same set of genes appears to be expressed in boys and girls. The size of genetic and environmental contributions remains the same across the ages studied. Stability in OA and AP is accounted for by genetic influences. Children who do not display OA or AP at a given age are unlikely to develop these problems at a subsequent age.

Attention Deficit Disorder with Hyperactivity↗
PubMed2003

Heritability of attention problems in children: I. cross-sectional results from a study of twins, age 3-12 years.

Multiple twin studies of attention problems (AP) from the Child Behavior Checklist or ADHD from the DSM criteria have reported on the genetic and environmental influences on these behaviors. The majority of these have studied AP and ADHD symptoms in twin samples combined across wide age spans, combined rater information and both genders. Thus, it is possible that the results are complicated by developmental, informant, and gender differences. The purpose of this study was to assess for the genetic and environmental contributions to overactive behavior (a syndrome highly related to AP in 7-, 10-, and 12-years olds) in 3-years olds (3,671 twin pairs), and attention problems in 7- (3,373 twin pairs), 10- (2,485 twin pairs), and 12-years olds (1,305 twin pairs) while controlling for developmental, gender and rater contrast contributions. Using a cross-sectional twin design, contributions from genetic additive, genetic dominance, unique environmental and rater contrast effects were estimated for CBCL maternal reports. We found that genetic influences on overactive behavior and attention problems are high across an age span that covers pre-school and elementary school age. Although girls display less problem behavior compared to boys, heritability estimates were found equal for both genders at each age. Environmental experiences that are unique to the individual accounted for the remaining influence. At the age of 3 years, a rater contrast effect was detected. We hypothesize that the contrast effect represents a maternal rater bias effect that is dependent on the age of the twins. The implications of these findings are discussed with reference to the clinical setting and in the context of future research.

Age Factors↗
PubMed2003

Heritability of cortisol levels: review and simultaneous analysis of twin studies.

Cortisol has a pivotal role in physical and mental health, but relatively few studies have paid attention to individual differences in cortisol levels and the etiology of these differences, in particular their possible genetic basis. In this article we review the existing literature on the heritability of cortisol levels. Most of the studies, which have been carried out in genetically informative samples, lack methodological consistency with regard to frequency and timing of sample collection. The circadian rhythm in cortisol levels was often not taken into account. A power analysis shows that none of these studies used adequate sample sizes to distinguish genetic from shared environmental influences as a cause for familial aggregation. Results of a simultaneous analysis of 5 comparable twin studies suggest a heritability of 62%. Hence, we conclude that, to understand the contribution of genetic and (shared) environmental influences to variation in basal cortisol levels, future studies should be designed more rigorously with strict collection and sampling protocols, sufficient sample size and repeated measures across multiple days.

Circadian Rhythm↗
PubMed2003

Causes of stability of aggression from early childhood to adolescence: a longitudinal genetic analysis in Dutch twins.

This study investigated the contribution of genetic and environmental influences on the stability of aggressive behavior from early childhood to adolescence. Two developmental models, the simplex model and the common factor model, were tested to study the underlying processes of stability and change. Measures of aggressive behavior (AGG) were obtained from maternal CBCL data as part of a large ongoing longitudinal study of the Netherlands Twin Registers (NTR) and included data from 6488 three-year-old twin pairs, 5475 seven-year-old twin pairs, 2983 ten-year-old twin pairs, and 1509 twelve-year-old twin pairs. AGG showed moderate to high stability during childhood. The stability coefficients ranged from 0.41 to 0.77 across varying intervals. Averaged across boys and girls, genetic factors accounted for approximately 65% of the total stability. Longitudinal genetic analysis indicated a simplex model for genetic effects, which suggests a dynamic development process consisting of transmission of existing genetic effects interacting with new genetic influences. This is especially true at age 7, when the influence of new genetic factors was large. Shared environmental factors accounted for approximately 25% of phenotypic stability, and it seemed that a stable set of the same shared environmental factors underlay the development of AGG. Nonshared environmental factors, when important, are age specific. Sex-specific differences for stability were identified. For boys, genetic influences were greater, whereas for girls shared environmental factors were more important. These data support the idea that both genetic and environmental influences play a role in the stability of AGG from age 3 to 12.

Aggression↗
PubMed2003

Individual differences in aggression: genetic analyses by age, gender, and informant in 3-, 7-, and 10-year-old Dutch twins.

Aggression in humans is associated with substantial morbidity and mortality. In this study we report on the aggressive behavior syndrome (AGG) in young children as defined by the Child Behavior Checklist (CBCL) and the Teacher Report Form (TRF). We assessed aggression in a large sample of Dutch twins at ages 3, 7, and 10 years. The purpose of this study was three-fold. First, we determined the number of children who are "clinically deviant" on the AGG scale. Second, we assessed the genetic and environmental contributions to AGG for the maternal, paternal, and teacher ratings at each age, for boys and girls. Third, we explored issues of rater bias by analyzing parental and teacher data simultaneously. CBCL data were available from mothers on 6436 three-year-old, 5451 seven-year-old, and 2972 ten-year-old twin pairs and CBCL data from fathers on 4207 three-year-old, 4269 seven-year-old, and 2295 ten-year-old twin pairs. Teacher report data from the TRF were collected for 1036 seven-year-old and 903 ten-year-old twin pairs from the Netherlands Twin Registry. Structural equation modeling was employed to obtain genetic and environmental estimates at each age. Analyses were conducted separately by age and informant, as well as simultaneously, for all informants. Differences in raw scores across gender were found, with boys being rated as more aggressive than girls by all informants. Mothers reported more symptoms than fathers, who reported more symptoms than teachers. Evidence for moderate to high genetic influence (51%-72%) was seen for AGG by all three informants at all ages with only small sex differences in heritability estimates. Best fitting models for AGG by parent reports also included a small contribution of common environment. The largest sex differences in heritabilities were seen at age 10. Contributions of common (13%-27%) and unique (16%-31%) environment were small to moderate. There was some evidence of genetic dominance by teacher report for 10-year-old girls.

Adolescent↗
PubMed2003

Co-occurrence of aggressive behavior and rule-breaking behavior at age 12: multi-rater analyses.

Aggressive Behavior (AGG) and Rule-Breaking Behavior (RB) are two of the eight CBCL syndromes. The phenotypic correlation between AGG and RB ranges from.48 to.76, and varies depending on the rater and the sex of the child. Prevalence of AGG and RB (i.e., T > or = 67) is in the range of 6%-7% in both boys and girls. Fifty percent to 60% of the children who are deviant on AGG are also deviant on RB and vice versa. Why so many children show problem behavior in the clinical range for both syndromes is unclear. This co-occurrence could be due to genetic factors influencing both traits, to environmental factors influencing both traits, or to both. The purpose of this study is to use a genetically informative sample to estimate genetic and environmental influences on AGG and RB and to investigate the etiology of the co-occurrence of both behaviors. We do this using multiple informants to take into account underlying sources of parental agreement and disagreement in ratings of their offspring. To this end, mother and father ratings of AGG and RB were collected by using the Child Behavior Checklist in a large sample of 12-year-old twins. Parental agreement is represented by an interparent correlation in the range of .53-.76, depending on phenotype (AGG or RB) and sex of the child. Genetic influences account for 79% and 69% of the individual differences in RB and AGG behavior (defined as AGG and RB on which both parents do agree) in boys. In girls 56% and 72% of the variance in RB and AGG are accounted for by genetic factors. Shared environmental influences are significant for RB in girls only, explaining 23% of the total variance. Eighty percent of the covariance between AGG and RB, similarly assessed by both parents, can be explained by genetic influences. So, co-occurrence in AGG and RB is mainly caused by a common set of genes. Parental disagreement seems to be a combination of so-called rater bias and of parental specific views.

Aggression↗
PubMed2002

[Correlation of diffusion-weighted magnetic resonance imaging with neurological deficits in sporadic Creutzfeldt-Jakob Disease].

This case report describes the sporadic Creutzfeldt-Jakob disease (CJD) of a 53-year-old man who initially complained about vertigo and dizziness. Within 18 weeks, he developed impaired memory, hemineglect, and sensory impairment of the left half of the body. A CSF tap was positive for 14-3-3 protein and showed increased tau protein, neuron-specific enolase (NSE), and the astroglial protein S-100 B. The EEG showed right temporal sharp waves without periodicity. Diffusion-weighted MRI revealed hyperintensities in the right temporo-occipital cortex which corresponded well with hypometabolic areas in a PET scan and the neurological and neuropsychological deficits. The morphological FLAIR T2 MRI showed no pathological changes. Within 20 weeks, the patient developed severe dementia with decreased spatial orientation and myoclonia, became incontinent, and was confined to bed. He died within 22 weeks after the first presentation of symptoms.

Creutzfeldt-Jakob Syndrome↗
PubMed2002

The neural correlates of intentional and incidental self processing.

The neuroscientific study of the 'Self' is just beginning to emerge. We used functional Magnetic Resonance Imaging (fMRI) to investigate cerebral activation while subjects processed words describing personality traits and physical features, in two experiments with contrasting designs: incidental and intentional. In the first experiment (intentional self processing), subjects were presented with personality trait adjectives and made judgements as to their self descriptiveness (versus non self descriptiveness). In the second experiment (incidental self processing), subjects categorised words according to whether they described physical versus psychological attributes, while unaware that the words had been arranged in blocks according to self descriptiveness. The subjects had previously rated all words for self descriptiveness 6 weeks prior to the scanning session. A reaction time advantage was present in both experiments for self descriptive trait words, suggesting a facilitation effect. Common areas of activation for the two experiments included the left superior parietal lobe, with adjacent regions of the lateral prefrontal cortex also active in both experiments. Differential signal changes were present in the left precuneus for the intentional and the right middle temporal gyrus for the incidental experiment. The results suggest that self processing involves distinct processes and can occur on more than one cognitive level with corresponding functional neuroanatomic correlates in areas previously implicated in the awareness of one's own state.

Adult↗
PubMed2002

Genetic and environmental influences on the development of intelligence.

Measures of intelligence were collected in 209 twin pairs at 5, 7, 10, and 12 years of age, as part of a longitudinal project on intelligence, brain function, and behavioral problems. Intelligence was measured at 5, 7, and 10 years of age with the RAKIT, a well-known Dutch intelligence test, consisting of 6 subscales. At 12 years of age, the complete WISC-R was administered (12 subscales). Both intelligence tests resulted in a measure of full-scale IQ (FSIQ). Participation rate is around 93% at age 12. Correlation coefficients over time are high: (r(5-7) = .65; r(5-10) = .65; r(5-12) = .64; r(7-10) = .72; r(7-12) = .69 and r(10-12) = .78). Genetic analyses show significant heritabilities at all ages, with the expected increase of genetic influences and decrease of shared environmental influences over the years. Genetic influences seem to be the main driving force behind continuity in general cognitive ability, represented by a common factor influencing FSIQ at all ages. Shared environmental influences are responsible for stability as well as change in the development of cognitive abilities, represented by a common factor influencing FSIQ at all ages and age-specific influences, respectively.

Child↗
PubMed2002

Heart-rate variability (HRV) in the ECG trace of routine EEGs: fast monitoring for the anticholinergic effects of clozapine and olanzapine?

Drug monitoring in psychiatry usually serves psychoactive drug plasma concentration measurement. Anticholinergic properties offer a faster approach to monitoring pharmacodynamic intraindividual effects of the drug by measuring their effects on heart rate variability (HRV), which is sympathetically and parasympathetically controlled via cholinergic synapses. The plasma concentrations of the atypical antipsychotics clozapine and olanzapine correlated with parameters of HRV in 59 patients suffering from schizophrenia or schizoaffective disorder. HRV during 4 minutes at rest was extracted from the ECG trace of a routine digital EEG registration in addition to blood sampling for plasma concentration measurement (HPLC method). We calculated sympathetically and parasympathetically controlled heart frequency bands (low, medium and high frequency) and other HRV parameters, coefficient of variation (CV), and root mean square of successive differences (RMSSD). All HRV parameters were significantly more impaired in clozapine patients (n = 33, mean clozapine plasma concentration 331 +/- 294 ng/ml) than in olanzapine patients (n = 26, mean olanzapine plasma concentration 42 +/- 32 ng/ml) and demonstrated 1.7 - 4.8 times the cardiac anticholinergic properties of clozapine in vivo. 14 out of 14 patients with a CV beyond 3.2 % had clozapine plasma concentrations below the proposed optimal therapeutic concentration of 350 ng/ml. All HRV parameters were inversely and significantly correlated with the clozapine plasma concentrations (such as lgCV: r = - 0.73, p < 0.001) and, to a lesser extent, with the olanzapine plasma concentrations (lgCV r = - 0.44, p < 0.05). These results underline the potential clinical value of HRV parameter extraction from routine ECGs in predicting plasma concentrations and objective individual neurocardiac effects of drugs with anticholinergic properties.

Adolescent↗
PubMed2002

Increased serum levels of CD95 in Alzheimer's disease.

There is growing evidence for a role of apoptosis in Alzheimer's disease (AD). Recent findings suggest an increased susceptibility of lymphocytes to apoptosis in AD. To prove the hypothesis of systemic alterations in the apoptotic balance in AD, serum and cerebrospinal fluid levels of soluble CD95, which is known to mediate apoptosis, were measured. In the serum, AD patients exhibited significantly higher levels of CD95 than the controls (p = 0.017), suggesting an involvement of peripheral markers in AD.

Aged↗