Vismodegib for periocular basal cell carcinoma: an international multicentre case series.

INTRODUCTION: Vismodegib (Erivedge, Genentech) is a first-in-class inhibitor of the hedgehog (Hh) pathway, which is licensed for use in locally advanced basal cell carcinoma (BCC) and metastatic BCC. The National Institute for Health and Care Excellence withdrew recommendation for use of vismodegib secondary to a lack of data comparing vismodegib to standard supportive care. The purpose of this multicentre, international case series is to report outcomes of patients with locally advanced periocular BCC who have been treated with vismodegib. METHODS: The medical records of all patients treated with vismodegib were retrospectively reviewed across seven institutions in the United Kingdom, Australia, and New Zealand. RESULTS: Thirteen patients were identified. Seven (54%) patients were male. All BCCs were ill-defined, with seven (58%) having orbital involvement at presentation. Median treatment time was 7 months (range 2-36 months). Eleven out of 13 patients developed side effects, the most common being fatigue in six patients (46%). Median follow-up was 24 months (range 12-48 months). Complete response was found in 5/13 patients (38%) and a partial response in 8/13 patients (62%). Six patients had further surgery after vismodegib, with three classed as globe-sparing operations. Three patients developed recurrence (23%). Three patients (23%) ultimately underwent exenteration. DISCUSSION: This study demonstrates vismodegib to be a well-tolerated treatment which may, in some cases, facilitate globe-sparing surgery and hence avoid disfiguring operations such as exenteration. Uncertainty does remain regarding the long-term outcomes of patients treated with vismodegib.

Reduced emotional empathy in adults with subclinical ADHD: evidence from the empathy and systemizing quotient.

Studies in children with ADHD suggest impairments in social cognitive functions, whereas studies in adults with ADHD are scarce and inconclusive. The aim of this study was to investigate the relationship between ADHD traits and self-reported social cognitive style in a sample of adults from the general population. For this purpose, a community sample of 685 adults filled out online self-report questionnaires about ADHD symptoms (ADHD Rating Scale, ARS), social cognitive functioning and friendships. The Empathy Quotient (EQ) with the subscales Cognitive Empathy (CE), Emotional Empathy (EE) and Social Skills (SS), and the Systemizing Quotient (SQ) were included for measuring social cognitive style and the Friendship Questionnaire (FQ) for the quality of friendships. Participants who met the DSM-5 criteria on the ARS ('subclinical ADHD'; n = 56) were compared regarding their social cognitive functioning scores with a control group (n = 56) that was matched for age, sex and student status. With small effect sizes, the subclinical ADHD group showed reduced EE scores on the EQ and a more male social cognitive profile. This result was not influenced by sex or ADHD subtype. This study points to a relationship between traits of ADHD and the emotional aspect of empathy, whereas more complex aspects of empathy were unrelated. These findings should be corroborated in clinical patients with ADHD, employing neuropsychological tests rather than self-report questionnaires.

Phosphocholine - an agonist of metabotropic but not of ionotropic functions of α9-containing nicotinic acetylcholine receptors.

We demonstrated previously that phosphocholine and phosphocholine-modified macromolecules efficiently inhibit ATP-dependent release of interleukin-1ß from human and murine monocytes by a mechanism involving nicotinic acetylcholine receptors (nAChR). Interleukin-1ß is a potent pro-inflammatory cytokine of innate immunity that plays pivotal roles in host defence. Control of interleukin-1ß release is vital as excessively high systemic levels cause life threatening inflammatory diseases. In spite of its structural similarity to acetylcholine, there are no other reports on interactions of phosphocholine with nAChR. In this study, we demonstrate that phosphocholine inhibits ion-channel function of ATP receptor P2X7 in monocytic cells via nAChR containing α9 and α10 subunits. In stark contrast to choline, phosphocholine does not evoke ion current responses in Xenopus laevis oocytes, which heterologously express functional homomeric nAChR composed of α9 subunits or heteromeric receptors containing α9 and α10 subunits. Preincubation of these oocytes with phosphocholine, however, attenuated choline-induced ion current changes, suggesting that phosphocholine may act as a silent agonist. We conclude that phophocholine activates immuno-modulatory nAChR expressed by monocytes but does not stimulate canonical ionotropic receptor functions.

Oxytocin enhances orienting to social information in a selective group of high-functioning male adults with autism spectrum disorder.

OBJECTIVE: The study investigated the effects of nasally administered oxytocin on neurophysiological orienting to empathy-evoking pictures in normally intelligent male adults with and without an autism spectrum disorder (ASD). It further investigated whether these effects might be moderated by the individual's approach and avoidance tendencies. METHODS: All subjects participated in a randomised double-blind placebo controlled crossover trial where either oxytocin (OXT) or placebo was administered preceding the viewing of affective pictures.The pictures, selected from the International Affective Picture System (IAPS), represented a systematic variation of pleasant, unpleasant and neutral scenes with and without humans. Both cardiac (ECR) and cortical (LPP) evoked orienting responses were measured and both were enhanced for the pictures with humans, in particular for the unpleasant ones. RESULTS: No significant group differences were found, nor were there any treatment effects. Moderator analysis, however, demonstrated that OXT did enhance orienting to affective pictures with humansin male adults with ASD who are easily distressed when seeing others in stressful situations and in healthy males who are highly sensitive to anticipated punishment and criticism or have a low drive for goal achievement. CONCLUSION: Individual differences in stress-related avoidance tendencies should be taken into account when considering OXT as a treatment of social deficiencies in autism.

The Empathy and Systemizing Quotient: The Psychometric Properties of the Dutch Version and a Review of the Cross-Cultural Stability.

The 'Empathy Quotient' (EQ) and 'Systemizing Quotient' (SQ) are used worldwide to measure people's empathizing and systemizing cognitive styles. This study investigates the psychometric properties of the Dutch EQ and SQ in healthy participants (n = 685), and high functioning males with autism spectrum disorder (n = 42). Factor analysis provided support for three subscales of the abridged 28-item EQ: Cognitive Empathy, Emotional Empathy and Social Skills. Overall, the Dutch EQ and SQ appeared reliable and valid tools to assess empathizing and systemizing cognitive style in healthy adults and high functioning adults with autism. The literature showed good cross-cultural stability of the SQ and EQ in Western countries, but in Asian countries EQ is less stable and less sensitive to sex differences.

Are there sex differences in ERPs related to processing empathy-evoking pictures?

OBJECTIVE: This study aimed to investigate sex differences in the temporal dynamics of experiencing empathy by using electrophysiological measurements. METHODS: Twenty-five females and 27 males viewed 414 pictures of the International affective picture system varying in emotional valence (positive, negative and neutral) and presence of humans (human and scenes). EEG event related potentials (ERPs) were obtained and correlations were computed with self-reported empathy. RESULTS: Compared to males, females showed increased anterior N2 and parietal LPP amplitudes to humans contrasted with scenes (independent of emotional valence) and to negative contrasted with neutral emotions (independent of human presence). Independent of sex the N1 and anterior N2 were specifically increased for positive human emotions and the parietal LPP for negative human emotions. Across sexes, the N2 and LPP human emotion effects and LPP human effects were associated with self-reported affective empathy, but not with cognitive empathy. CONCLUSIONS: This study provides electrophysiological evidence that women prioritize the processing of socially relevant and negative emotional information, but that women did not show enhanced brain potentials to pictures with positive or negative emotions in humans.

The gasotransmitter hydrogen sulphide decreases Na⁺ transport across pulmonary epithelial cells.

BACKGROUND AND PURPOSE The transepithelial absorption of Na(+) in the lungs is crucial for the maintenance of the volume and composition of epithelial lining fluid. The regulation of Na(+) transport is essential, because hypo- or hyperabsorption of Na(+) is associated with lung diseases such as pulmonary oedema or cystic fibrosis. This study investigated the effects of the gaseous signalling molecule hydrogen sulphide (H(2) S) on Na(+) absorption across pulmonary epithelial cells. EXPERIMENTAL APPROACH Ion transport processes were electrophysiologically assessed in Ussing chambers on H441 cells grown on permeable supports at air/liquid interface and on native tracheal preparations of pigs and mice. The effects of H(2)S were further investigated on Na(+) channels expressed in Xenopus oocytes and Na(+) /K(+)-ATPase activity in vitro. Membrane abundance of Na(+) /K(+)-ATPase was determined by surface biotinylation and Western blot. Cellular ATP concentrations were measured colorimetrically, and cytosolic Ca(2+) concentrations were measured with Fura-2. KEY RESULTS H(2)S rapidly and reversibly inhibited Na(+) transport in all the models employed. H(2)S had no effect on Na(+) channels, whereas it decreased Na(+) /K(+)-ATPase currents. H(2)S did not affect the membrane abundance of Na(+) /K(+)-ATPase, its metabolic or calcium-dependent regulation, or its direct activity. However, H(2)S inhibited basolateral calcium-dependent K(+) channels, which consequently decreased Na(+) absorption by H441 monolayers. CONCLUSIONS AND IMPLICATIONS H(2) S impairs pulmonary transepithelial Na(+) absorption, mainly by inhibiting basolateral Ca(2+)-dependent K(+) channels. These data suggest that the H(2)S signalling system might represent a novel pharmacological target for modifying pulmonary transepithelial Na(+) transport.

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.

Influence of the dopamine agonist alpha-dihydroergocryptine on the pharmacokinetics of levodopa in patients with Parkinson's disease.

This study investigated whether chronic coadministration of alpha-dihydroergocryptine (DHEC) altered the plasma pharmacokinetics of individualized treatments with levodopa in 12 patients with Parkinson's disease. Steady-state pharmacokinetics of plasma levodopa (L-Dopa) under combined treatment were compared with those under treatment with L-Dopa alone. There was no evidence of increased exposure to L-Dopa caused by concomitant treatment with DHEC. In contrast, additional treatment with DHEC reduced the overall exposure to L-Dopa (17.5% reduction in area under the curve; 95% CI: 23%-6%). This effect was small but statistically significant for the area under the plasma concentration-time curve, whereas tmax (time of maximum plasma concentration) and peak-to-trough fluctuation were not affected. Cmax (maximum plasma concentration), on average, was reduced to a similar extent (-14.5%; 95% CI: 38% to -17%), albeit not significantly. The magnitude of the interaction does not suggest changing the current clinical practice of up-titrating DHEC and subsequently adapting L-Dopa to the individual needs of patients.

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.

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.

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.

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.

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.

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.

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.

Cardiovasculaire adaptiviteit aan de verrichting van aandachts-taken bij kinderen met contact- en communicatieproblemen.

A psychofysiological study of the cardiac adaptivity to attention-demanding reaction time tasks demonstrated that children with a lesser variant of the pervasive developmental disorder (DSM-IV: PDDNOS) exhibit less cardiac responsiveness to attention tasks than healthy children do. We studied changes in heart rate variability (HRV), which were measured in a frequency band ranging from 0.07 to 0.14Hz. During the performance of an attention task, healthy children exhibited task load-related decreases in HRV. These decreases were found to be significantly smaller and not task load-related in a group of children with a PDDNOS who were judged to be not hyperactive. The decreases in HRV during task performance were almost absent in children with a PDDNOS who were moreover judged to be hyperactive. The magnitude of HRV decreases appeared to be significantly related to one of our task performance measures and to behaviour problems reported by the parents. Our results suggest a diminished vagal adaptivity to attention-demanding task situations in children with a PDDNOS, which is related to their resistance to unexpected changes in their daily routines.

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.

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.

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.