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Biomedical subjects

M Althaus

Publications and source records attributed to M Althaus.

At least 19 recordsLinked to original sources
PubMed2003

Face recognition in children with a pervasive developmental disorder not otherwise specified.

This study investigates the accuracy and speed of face recognition in children with a Pervasive Developmental Disorder Not Otherwise Specified (PDDNOS; DSM-IV, American Psychiatric Association [APA], 1994). The study includes a clinical group of 26 nonretarded 7- to 10-year-old children with PDDNOS and a control group of 65 normally developing children of the same age. Two computerized reaction time tasks were administered: a face recognition task and a control task designed to measure the recognition of abstract visuospatial patterns. The latter were either easy or difficult to distinguish from a set of alternative patterns. The normally developing children recognized the faces much faster than the hardly distinguishable abstract patterns. The children in the PDDNOS group needed an amount of time to recognize the faces that almost equalled the time they needed to recognize the abstract patterns that were difficult to distinguish. The results suggest that, when processing faces, children with PDDNOS use a strategy that is more attention-demanding and, hence, less automatic or "Gestalt-like" than the one used by the control children. The results are discussed in the light of a theory that explains the development of coherent mental representations.

Attention↗
PubMed2001

Erythromycin increases plasma concentrations of alpha-dihydroergocryptine in humans.

OBJECTIVE: Our objective was to investigate the potential for relevant pharmacotherapeutic interaction between cytochrome P4503A4 (CYP3A4)-inhibiting agents such as erythromycin and the dopamine agonist alpha-dihydroergocryptine (DHEC). METHODS: The study was carried out as a single-center, controlled, nonblinded, 2-way crossover clinical trial with randomly allocated period-balanced sequences, investigating two treatments of a single oral dose of 10 mg DHEC (on the morning of day 1), once administered alone (reference), once along with a 4-day treatment (days -2 to 1) of 500 mg erythromycin 3 times daily. Periods were separated by a washout of at least 14 days. Nine healthy white male volunteers, 22 to 42 years old, with a body weight range of 58 to 90 kg (body mass index, 20.2-25.1 kg x m(-2)) began the study. One subject discontinued prematurely, and 8 concluded the study in accordance with the study protocol. RESULTS: The plasma and urinary pharmacokinetics of DHEC and its metabolites were characterized by a large variability. Concomitant treatment with erythromycin led to respective increases of 9.5 (95% confidence interval [CI], 6.5 to 13.9) and 16.5 (95% CI, 8.7 to 31.5) times the maximum observed plasma drug concentration and the area under the time course of the plasma concentrations up to the last quantifiable concentration after dosing of unchanged DHEC (determined by radioimmunoassay). The 24-hour urinary excretion was on average 11 times larger (95% CI, 5.9 to 20.7). Qualitatively similar findings were recorded for the total of DHEC plus metabolites (as determined by enzyme immunoassay). CONCLUSIONS: The concomitant use of erythromycin or similarly CYP3A4-inhibiting agents along with direct dopaminergic agonists such as the ergoline DHEC may cause a clinically relevant increase in pharmacokinetic exposure, which may induce exaggerated dopaminergic effects.

Administration, Oral↗
PubMed2001

Plasma and urine pharmacokinetics of the dopamine agonist alpha-dihydroergocryptine in patients with hepatic dysfunction.

OBJECTIVE: The aim of this study was to evaluate the pharmacokinetic behavior of unchanged alpha-dihydroergocryptine (DHEC, Almirid, Desitin Arzneimittel GmbH, Hamburg, Germany, under licence of Polichem S.A., Luxembourg) and total DHEC (unchanged DHEC and pooled metabolites) in plasma and urine in patients with impaired hepatic function, following administration of single oral doses. METHODS: The study was carried out according to an open, uncontrolled, parallel-group design, investigating two study groups: patients with hepatic dysfunction, i.e. with evidence of stable cirrhosis (n = 10) and age- and sex-matched healthy subjects (n = 8). Each subject received a single dose of 20 mg DHEC. Blood samples were taken at specified intervals up to 72 h after dosing and urine was collected fractionally for 24 h. Concentrations of unchanged DHEC were determined by RIA and concentrations of total DHEC (unchanged and pooled metabolites) by EIA. RESULTS: The plasma and urinary pharmacokinetics of DHEC and its metabolites were characterized by large variability. In patients with impaired hepatic function, the geometric mean Cmax and AUC(0-infinity) values for unchanged DHEC were 571.3 pg/ml (CV: 0.87) and 4038 pg x h/ml (CV: 1.04) and were approximately 2 times (2.04, 95% CI: 0.93 to 4.46 and 2.11, 95% CI: 0.58 to 7.73 for Cmax and AUC(0-infinity), respectively) larger than those measured in age-matched healthy controls. The 24-hour urinary excretion was approximately 3 times (3.41, 95% CI: 0.95 to 12.21) higher in patients with hepatic dysfunction. Similar results were obtained for total DHEC. CONCLUSIONS: The results reflect an increased systemic exposure in patients with impaired hepatic function which is not due to a reduced urinary excretion/elimination or reduced renal clearance. The most likely mechanism involved is a reduction in pre-systemic biotransformation. The observed range of effects on the pharmacokinetics of DHEC in patients with compromized hepatic function does not suggest the need to revise the dosage recommendations, since treatment with DHEC is generally started with low doses and is slowly up-titrated according to the individual response and the occurrence of adverse effects. Nevertheless, lower maintenance doses are likely to be achieved.

Adolescent↗
PubMed2000

The dopamine D2 receptor agonist alpha-dihydroergocryptine modulates voltage-gated sodium channels in the rat caudate-putamen.

Alpha-Dihydroergocryptine (alpha-DHEC), a Dopamine (DA) D2 receptor agonist, is widely used as dopaminergic drug in the treatment of Parkinson's disease. To study the mechanisms involved in the signal transduction process induced by alpha-DHEC on the presynaptic site of the dopaminergic neuron, we incubated slices of the rat caudate-putamen with alpha-DHEC and the indicated substances in static chambers. Following incubation the resulting DA outflow was measured by high-performance-liquid chromatography with electrochemical detection. The addition of alpha-DHEC (10 microM-0.1mM) did not modulate basal DA outflow. Activation of voltage-gated sodium channels by veratridine (VER) from low to relatively high concentrations (1-10 microM) led to a concentration-dependent increase of DA outflow. Using concentrations as high as 10 microM a dramatic increase of DA levels (600% of baseline levels) was observed. The ability of VER to provoke DA release was sensitive to the addition of tetrodotoxin (TTX) and was completely blocked by 1 mM TTX. Coincubation of alpha-DHEC (10microM-0.1mM) and VER (10microM) reduced VER-stimulated DA outflow in a concentration-dependent manner. The time-concentration course of VER-induced DA outflow was not modulated by alpha-DHEC. As described in our earlier studies, the specific D2 receptor antagonist (-)sulpiride (SLP) concentration-dependently enhances extracellular DA levels. Addition of alpha-DHEC almost completely blocked SLP-induced DA-outflow. When slices were incubated with the non-selective DA receptor agonist haloperidol (HLP, 0.1 mM) the effect of alpha-DHEC on VER-induced DA outflow was partially but not completely abolished. These data strongly suggest that the effect of alpha-DHEC on the presynaptic site implies an activation of D2 receptors as well as an inhibitory action on voltage-gated sodium channels. Alpha-DHEC seems to modulate voltage-gated sodium channels in part independently from DA receptors since blockade of D2 receptors with saturating concentrations of haloperidol did not completely abolish its effect. Based on our data we have no evidence that voltage-gated potassium channels, N-type calcium channels or D1, D3-receptors are involved in the action of alpha-DHEC at the presynaptic site of the dopaminergic neuron. The results give one rationale for the proposed neuroprotective effect of alpha-DHEC.

Animals↗
PubMed2000

How unspecified are disorders of children with a pervasive developmental disorder not otherwise specified? A study of social problems in children with PDD-NOS and ADHD.

This study examines possible differences and similarities between social behaviour problems in children with problems classified as pervasive developmental disorder not otherwise specified (PDD-NOS) and a group of children with problems classified as ADHD, as measured by parent questionnaires. The instruments involved were the CBCL (Child Behaviour Checklist), the ABC (Autism Behaviour Checklist) and a new instrument: the CSBQ (Children's Social Behaviour Questionnaire). In comparing the PDD-NOS group and the ADHD group, the results show that, according to parent reports, both groups have severe problems in executing appropriate social behaviour, but the PDD-NOS group can be distinguished from the ADHD group by the nature and the extent of these problems. The PDD-NOS group had significantly more social problems (as measured by the CBCL Social scale), withdrawn problems (as measured by the CBCL Withdrawn scale) and PDD-specific problems (as measured on the ABC Relating scale, the ABC Language scale, the CSBQ total score, the CSBQ Social Interaction scale and CBSQ Communication scale). In addition, although the descriptions of the social problems are global, i.e. on scale level, the results also show that the social problems of PDD-NOS children can be positively formulated and described as at least including severe social interaction problems, withdrawn behaviours and communication problems.

Attention Deficit Disorder with Hyperactivity↗
PubMed2000

Study on the interaction of the dopamine agonist alpha-dihydroergocryptine with the pharmacokinetics of digoxin.

AIM: The study was carried out to explore the potential for pharmacokinetic interaction of a single oral dose of alpha-dihydroergocryptine (CAS 14271-05-7, DHEC, Almirid) with digoxin. METHODS: The serum pharmacokinetics of digoxin were analysed after the administration of single oral doses of 0.5 mg digoxin administered either alone or concomitantly with 20 mg DHEC according to a randomised, non-blinded, two-period cross-over design, with study periods 2 weeks apart. Twelve healthy male subjects, 23 to 39 years of age were enrolled and were investigated in accordance with the protocol. Venous blood was sampled up to 48 h after dosing. Concentrations of digoxin in serum were determined by a competitive radioimmunoassay. RESULTS: The mean Cmax were 1.97 +/- 0.87 (after a median tmax of 1 h) and 2.05 +/- 0.95 ng/ml (after a median tmax of 0.83 h) after the administration of digoxin with (test) and without (reference) concomitant DHEC, respectively; the corresponding estimated treatment ratio for test: reference was 0.939, 95% CI: 0.781 to 1.129. The mean AUC(0-48) were 13.6 +/- 5.0 ng.h/ml and 13.3 +/- 4.7 ng.h/ml for the test and reference treatment, respectively; the corresponding estimated treatment ratio for test: reference was 1.011, 95% CI: 0.866 to 1.142. In addition, no clinically significant changes were observed by ECG monitoring. The tolerability of digoxin alone was good, significantly more adverse events occurred when co-administered with DHEC; these corresponded with the known adverse reaction profile and were of moderate intensity. No premature study termination was thus necessary. CONCLUSION: The present study did not demonstrate clinically relevant interaction of a single dose of DHEC on the pharmacokinetics of digoxin. On the basis of these observations there is no indication for an a priori adjustment of the dose of digoxin when concomitant treatment with DHEC is initiated.

Adolescent↗
PubMed2000

In vitro identification of the cytochrome P450 isoform responsible for the metabolism of alpha-dihydroergocryptine.

1. The in vitro metabolism of alpha-dihydroergocryptine (DHEC, Almirid), an ergot-derived dopamine agonist for the treatment of Parkinson's disease, has been studied in cultured cell lines following incubation with DHEC. Human hepatocytes as well as two sets of metabolically competent cell lines expressing one single human cytochrome P450 (1A1, 1A2, 1B1, 2A6, 2C8, 2C9, 2C18, 2C19, 2D6, 2E1, 3A4) were used. 2. Mono- and dihydroxy metabolites of DHEC could only be detected in the culture media of the cell line expressing human cytochrome CYP3A4. The same metabolites were found in the media of cultured human hepatocytes derived from three different donors. After 24-h incubation with 1 microM DHEC, approximately 60% mono- and approximately 20% dihydroxy metabolites were detected, i.e. approximately 80% of DHEC was metabolized. Further, DHEC demonstrated an inhibitory effect on CYP3A4-mediated testosterone metabolism and additionally could induce CYP3A4 and CYP2E1 mRNA when added at 10 microM to cultured human hepatocytes. 3. The data suggest that DHEC metabolism in humans is primarily mediated by the CYP3A4 isoform. The results are in accordance with findings derived from other ergot alkaloids.

Aged↗
PubMed1999

Cardiac adaptivity to attention-demanding tasks in children with a pervasive developmental disorder not otherwise specified (PDD-NOS).

BACKGROUND: Decreases in heart rate variability (HRV) have been repeatedly demonstrated to be an index of effort allocation to attention-demanding tasks. Children with autistic-type problems in social interaction and in adapting to unfamiliar situations (DSM-IV: PDD-NOS) have been shown to have specific attention deficits. These children were hypothesized to exhibit less cardiac adaptivity to attention-demanding tasks. METHODS: Two groups of 18 children with PDD-NOS, judged to be hyperactive and nonhyperactive, were compared to 18 healthy children with respect to their performances on a visual attention task and the differences in HRV measured during periods of task performance and periods of rest. RESULTS: Compared to the control group, both clinical groups were found to have a stronger capacity limitation in processing high loads of information, and to be less capable of maintaining a stable task performance throughout the whole task. Both clinical groups showed significantly less decreases in HRV during the periods of task performance. The magnitude of rest-task differences in HRV was found to correlate significantly with a behavioral measure of resistance to unexpected changes in daily routines. CONCLUSIONS: Children with PDD-NOS are significantly less flexible in their autonomic adaptation to attention-demanding tasks. The findings are interpreted as reflecting a deficiency in the functional organization of those neural pathways that provide cortical control of the visceral efferents.

Adaptation, Physiological↗
PubMed1998

Influence of respiratory activity on the cardiac response pattern to mental effort.

A group of 32 healthy adult volunteers completed three blocks of a reaction time task that varied in the degree of controlled processing load. A rest period preceded each of the task blocks. The task blocks were presented in the order of either increasing or decreasing cognitive load. For each of the six periods, mean values and spectral measures of heart rate and respiration variability were calculated. The spectral measures were obtained for three different frequency bands. Differences between the cardiac measures of the task and preceding rest periods were compared with respect to differences in task load and the order of task presentation. All comparisons were carried out while adjusting for respiratory variability in the corresponding frequency band. The frequency band in which task load-related changes in heart rate variability became manifest appeared to be dependent on the individual's breathing pattern.

Adult↗
PubMed1995

Emotional role-taking abilities of children with a pervasive developmental disorder not otherwise specified.

Seven to 12-year-old children with a Pervasive Developmental Disorder Not Otherwise Specified (PDDNOS) were compared with normal, healthy children of the same age and sex on three different emotional role-taking tasks. In these tasks, children had to use person-specific information to make an inference about another child's emotional reaction and behaviour, Significant differences were found between the PDDNOS group and control group: PDDNOS children performed worse on all three role-taking tasks. However, the differences on one of these tasks could be completely explained by intelligence differences between the two groups. On the other tasks, differences could not or be partially explained by intelligence differences. The results of this study led to the formulation of a more specific hypothesis, namely that PDDNOS children might have problems interpreting social information when affectively charged background information has to be used.

Aptitude↗
PubMed1995

Lack of effect of clonidine on stuttering in children.

OBJECTIVE: The authors studied the effects of the alpha 2-receptor agonist clonidine on stuttering in children. METHOD: Using a double-blind crossover study, they gave placebo or 4 micrograms/kg body weight per day to 25 stuttering children who were 6-13 years old. Stuttering was measured by counting the occurrences of four elementary speech difficulties and by asking parents and teachers to give an overall impression of the amount of stuttering, as well as their impression of how troublesome the stuttering was to the children. RESULTS: Clonidine did not improve stuttering. CONCLUSIONS: Clonidine cannot be recommended as a useful drug for treating children who stutter.

Adolescent↗
PubMed1994

The assessment of individual differences between young children with a pervasive developmental disorder by means of behaviour scales which are derived from direct observation.

Data obtained by direct observation of 112 3-6-year-old normal children and 31 children with a pervasive developmental disorder aged 3-6 were used to construct behaviour scales by means of simultaneous component analysis. This is a technique for finding behaviour clusters (components) common to different groups by weighting the variables such that the resulting components maximize variance accounted for when summed over the groups (Milsap & Meredith, 1988, Psychometrika, 53, 123-134; Berge & Kiers, 1990, Nederlands Tijdschrift voor de Psychologie, 45, 221-226). An evaluation of the component structure that was found is given for both groups. Results show uncorrelated components for the normal group, while some of the same components are intercorrelated in the clinical group. Scales were constructed which are shown to have discriminative value with respect to subgroups within the group of patients.

Autistic Disorder↗
PubMed1993

[Reliability of assessment of audible stuttering behavior].

The authors examine the essential aspects of the behaviour of the stutterer as perceived by the ear and discuss the reliability of the appreciation. The method of molecular analysis of speech samples of children aged from 7 to 12 years is described. The conclusion is that using this method, four out of the six categories of children examined show complete concordance and can be repeated as required; this is particularly true insofar as elongations, blockages, repetitions and interjections are concerned. However, one cannot consider as valid criteria the length of the pauses and the quality of breathing during phonation.

Child↗
PubMed1992

Damaging backgrounds: later adjustment of international adoptees.

In this study of 2,148 international adoptees aged 10 to 15 years, the influence of early adverse experiences on later adjustment was examined. It was found that early neglect, abuse, and the number of changes of caretaking environment increased the risk for later maladjustment. The older the age of the child at placement, the greater the probability that the child had been subjected to psychosocial adversities. This association sufficiently explained the greater likelihood of later maladjustment with increasing age of the child at placement. Age at placement, as such, did not contribute to the prediction of later maladjustment, independent of the influence of early adversities. The present study underscores the importance that parents and professionals should obtain reliable and detailed information on the child's background and functioning before adoption. This study also showed that the majority of adopted children, even those with backgrounds known to be damaging, seemed to function quite well according to their parents' reports.

Adaptation, Psychological↗
PubMed1991

Joint occurrence of collagen mRNA containing cells and macrophages in human atherosclerotic vessels.

Cells with enhanced levels of collagen type I and III mRNA were identified and localized in frozen tissue sections from samples of human atherosclerotic renal and common iliac arteries by in situ hybridization using complementary 35S-labeled RNA probes. Serial sections were immunohistochemically stained for smooth muscle cells, monocytes, and differentiated macrophages. In the fibromuscular intima and in the fibrous plaques, cells with enhanced transcriptional activity were located mainly in the vicinity of differentiated macrophages. In three patients, lack of enhanced transcriptional activity in a proliferated intima was connected with complete absence of macrophages, thus indicating a quiescent stage of atherosclerosis. Immunohistochemical staining of serial sections for smooth muscle cells (SMC) revealed the presence of this cell type throughout the proliferated intima in atherosclerotic arteries including those areas in which enhanced collagen mRNAs were detected. The present results support the idea that macrophages play an important role in the activation of collagen synthesis in SMC of atherosclerotic vessel walls.

Adolescent↗
PubMed1990

Effects of murine recombinant interferon-gamma on rat liver fat storing cell proliferation, cluster formation and proteoglycan synthesis.

Rat liver fat storing cells (FSC, perisinusoidal lipocytes, Ito cells) in primary culture were exposed to various concentrations of murine recombinant interferon-gamma (rIFN-gamma) in the range of 1 to 50 units/mL medium for 72 hr. FSC kept in complete medium (10% fetal calf serum) showed a dose-dependent increase of both [3H]thymidine incorporation (up to 2.3-fold) and DNA content of culture. Reverse (inhibitory) effects were obtained with cells kept under serum-reduced (0.5% fetal calf serum) conditions. The synthesis of medium proteoglycans and of total cellular protein was not affected by rIFN-gamma. By bromodeoxyuridine-staining (BrdUrd) and phase contrast microscopy it is shown that rIFN-gamma stimulates strongly the cluster growth of FSC in culture. The cluster forming cells differ in their morphology and their cytoskeleton-staining from typical FSC. They were found to be mostly desmin and alpha-actin negative or weakly positive but highly proliferative. Because no contaminating fibroblasts and other cell types were detected in any appreciable amounts in the early cultures we conclude that the clustered cells might be a rapidly proliferating subpopulation of FSC, which is promoted by rIFN-gamma.

Animals↗