Therapeutic drug monitoring of zuclopenthixol in a double-blind placebo-controlled discontinuation study in adults with intellectual disabilities and aggressive behaviour.

The trial was a double-blind, placebo-controlled comparison with a discontinuation design. 49 mentally retarded patients with aggressive behaviour were treated with zuclopenthixol at a dose of 2-20 mg/d. At each visit the clinical effect was evaluated. Correlations between dose, serum concentration, and efficacy measures were calculated. The mean dose was 10.0 mg/day (±5.17); the mean serum concentration 4.19 ng/mL (±3.16). Associations of dosage, serum concentration and clinical efficiency did not result in coherent patterns. Correlations with clinical efficiency measures appeared to be contradictory for dosage and serum concentrations, respectively. As no consistent associations between dosage, serum concentration, and clinical efficiency measures were found, different hypotheses explaining the results are discussed.

Effects of zuclopenthixol on aggressive disruptive behavior in adults with mental retardation--a 2-year follow-up on a withdrawal study.

INTRODUCTION: People with mental retardation often display aggressive behavior against themselves or others making care within institutions or foster families difficult. Due to a lack of viable alternatives, antipsychotics of the first and second generations are often used for long-term treatment despite the fact that only data about short-term treatment exist. METHODS: A short-time withdrawal trial of 12 weeks (n = 39) was extended at open label to 2 years. 31 patients received zuclopenthixol after the end of the withdrawal and were examined using the same instruments as in the withdrawal period (DAS, MOAS, CGI). RESULTS: Patients still treated with zuclopenthixol after 2 years (n = 21) benefitted, compared to the drop-outs (n = 10). Analyses of time trends revealed an early effect of zuclopenthixol which could not be enhanced afterwards. DISCUSSION: Zuclopenthixol proved to be safe and effective to keep a lower rate of aggressive behavior in adults with mental retardation also over a longer period of time.

Modulation of motorcortical excitability by methylphenidate in adult voluntary test persons performing a go/nogo task.

This study investigated the interaction between motorcortical excitability (short interval cortical inhibition, intracortical facilitation and long interval cortical inhibition), different requirement conditions [choice reaction test (CRT), attention/go/nogo], and their pharmacological modulation by methylphenidate (MPH) in normal healthy adults (n = 31) using a transcranial magnetic stimulation paradigm. MPH was administered in a dosage of 1 mg/kg body weight, maximum 60 mg. Additionally, serum level and clearance of MPH were controlled. The statistical analysis of variance revealed a significant three-way interaction of 2 (MPH) x 3 (CRT) x 6 (ISI) predicting motor evoked potential amplitudes (P = 0.032, MPH none and full dose, n = 31). In order to compare effects of dosage an additional between-subjects factor (half vs. full MPH dose) was introduced. None of the interactions involving this between-subject factor reached statistical significance. Exploring interactions with MPH only, a 3 (MPH none, half and full dose) x 3 (CRT) x 6 (ISI) analysis of variance revealed significant two-way interactions for MPH x ISI (P = 0.040) and condition x ISI (P < 0.001, n = 18). Effects observed for MPH were strongest on facilitatory processes, weaker for intracortical inhibition. In sum, MPH seems to interact via striato-thalamo-cortical pathways with original motorcortical processes (ISI), to a lesser extent with task-dependent or behavioral parameters (CRT).

A double-blind placebo-controlled discontinuation study of zuclopenthixol for the treatment of aggressive disruptive behaviours in adults with mental retardation - secondary parameter analyses.

INTRODUCTION: Earlier studies showed risperidone to be effective in the treatment of aggression and self-injurious behaviour in adults with mental retardation but also having adverse side effects. This study was conducted to evaluate the effects of zuclopenthixol withdrawal. METHODS: After open treatment with zuclopenthixol (n=49) responders were randomly assigned to continue (n=19) or discontinue (n=20) zuclopenthixol treatment during a 12-week double-blind, placebo-controlled period. Effects were measured using the Disability Assessment Schedule (DAS), improvement on the Clinical Global Impression Scale (CGI-I), and the Nurse's Observation Scale for Inpatient Evaluation (NOSIE). RESULTS: Ten patients (20%) discontinued the study due to insufficient therapeutic effect or adverse events in the open period. EFFICACY: The superiority of zuclopenthixol over placebo among all randomized patients was supported not only by primary efficacy measure but also by the comparisons of mean scores of all secondary efficacy measures tested in a step-down-procedure (DAS, p<0.001; CGI-I, p<0.002, NOSIE, p<0.005). SAFETY: In both groups, one patient discontinued (5%) for adverse events. Adverse events were generally mild or moderate in severity. DISCUSSION: Zuclopenthixol proved to be safe and effective to keep a low rate of aggressive behaviour in adults with mental retardation.

[Legal aspects of hyperkinetic disorders/ADHD]. / HKS/ADHS und rechtliche Aspekte.

With a prevalence of 2-6%, hyperkinetic disorders (F 90, ICD-10) and disturbances of activity and attention (F 90.0, ADHD, ICD-10) are among the psychiatric disorders most commonly diagnosed in children, adolescents, and adults. Children and adolescents diagnosed with ADHD suffer from hyperactivity and deficits in attention and impulse control. Adults usually have problems focusing on one goal, maintaining their attention, modulating emotions effectively, structuring their tasks, and controlling impulses and in executive functions. Legal implications derive from core symptoms and from treatment with stimulants governed by legislation on narcotics. This paper discusses juridical aspects of ADHD in connection with the administration of medication at school, trips abroad within and outside the Schengen area, driving, competitive sports, military service, the increased risk of delinquency, the individual capacity to incur criminal responsibility, developmental criteria for the ability to act responsibly, and modalities for withdrawal treatment or treatment during detention.

Clinical management of traumatic bone cyst in children: a case report.

A case report of a traumatic bone cyst occurring in a 10-year-old girl which persisted after endodontic treatment of the teeth involved in lesion is presented. The importance of established clinical and radiographic diagnosis in order to avoid radical surgery or unnecessary endodontic treatment in children is discussed.

[Organic somatoform disorder. Case report]. / Transtorno somatoforme de causa orgânica. Relato de caso.

Based on the neuropsychological and imagenological evaluation of a frontal damaged patient with a somatoform disorder, we study the differential diagnosis of this condition compared to that of other patients: temporal or parietal damaged ones, schizophrenics, melancholics, obsessives, hypochondriacs and dismorphophobics.

[Emotionally-loaded narrative increases dyslogia in schizophrenics]. / Aumento da dislogia do discurso em narrativa emocionalmente carregada na esquizofrenia.

We tested the degree of dyslogia in the narrative of ten schizophrenic non-medicated outpatients while they narrated emotionally-loaded or neutral facts. The "emotional narratives" were much more dyslogic than the "neutral narratives". In order to explain these facts we evoke: 1. A fronto-temporo-limbic connection dysfunction would disturb an adequate cognitive treatment of emotions that would be, in this way, highly disruptive over logical processes. 2. A working memory/supervisory attentional system dysfunction that would produce both a loss of the normal connections among the fragments of speech and a lack of global strategical planning of the thought.

The effect of high external pressure on DPPC-cholesterol multilamellar vesicles: a pressure-tuning Fourier transform infrared spectroscopy study.

We have investigated the effect of incorporation of cholesterol on the barotropic phase behavior of aqueous dispersions of 1,2-dipalmitoylphosphatidylcholine (DPPC) using Fourier-transform infrared spectroscopy (FTIR) in combination with the diamond anvil technique. Infrared spectral parameters, such as the frequencies, intensities, bandshapes and band splittings have been used to detect structural and dynamical changes upon incorporation of cholesterol into the DPPC bilayer. Analysis of these spectral parameters yields information on conformer population, reorientational fluctuations, interchain interaction, hydrogen bonding, interdigitation packing, and phase transformations of the DPPC/cholesterol mixtures. We present FTIR data of aqueous DPPC dispersions at 0, 10, 20, 30, 40, and 50 mol% cholesterol in the pressure range from 0.001 to 20 kbar at two temperatures, 25 degrees C and 55 degrees C. In addition, comprehensive temperature dependent measurements in the range from 20 degrees C to 80 degrees C were performed at ambient pressure. Analysis of the CH2 symmetric and antisymmetric stretching modes yields information of the effect of cholesterol concentration on the phase transition phenomena occurring in the lipid bilayer. Observation of the correlation field splittings of the CH2 bending and rocking modes monitors structural changes and dynamical properties of the lipid mixtures. Cholesterol induces more orientational disorder of the lipid molecules in terms of an increase of the reorientational fluctuations of the molecules and twisting/torsion motions of the acyl chains in the gel phase even at elevated pressures. It therefore appears that one important role of cholesterol is to make the membrane insensitive to changes in external environment, such as high hydrostatic pressure. Increase of pressure leads to a decrease in half width of the C = O band contour of pure DPPC and of DPPC/cholesterol mixtures, especially for cholesterol concentrations equal and higher than 30 mol%, which might be due to a marked increase in free carbonyl groups. At high pressure part of the bound water from the interfacial zone of the membrane is withdrawn. Increase of the cholesterol concentration and increase in pressure have opposite effects on the population of free and hydrated carbonyl ester groups of DPPC in the gel phases.

Estimulaçäo alfa-adranérgica na secreçäo de hormônio de crescimento: comparaçäo da clonidina com guanabenz / Cepha adrenergic stimulation in growth hormone secretion: comparison between clonidine and guanabenz

Avaliamos o efeito da administraçäo aguda de clonidina e de guanabenz na secreçäo de hormônio de crescimento (GH0 em nove pacientes com deficiência isolada idiopática de GH (DGH), seis do sexo masculino e três do feminino, e em 15 indivíduos de baixa estatura sem deficiência de GH (CN), 11 do sexo masculino e quatro do feminino. Nesses últimos sob hipoglicemia induzida o pico de GH foi de 11,34 ñ 4,48ng/ml e no teste seqüencial exercício L-DOP o pico foi de 12,97 ñ 3,94ng/ml (Mñep). Sob a a çäo da clonidina e do guanabenz os CN apresentaram picos de GH de 22,07 ñ 3,2 e 19,24 ñ 2,26ng/ml respectivamente. Esses resultados näo foram estatisticamente diferentes daqueles obtidos com os testes clássicos de liberaçäo de GH. Os pacientes com DGH näo respoderam a nenhum dos testes de liberaçäo utilizados. Nossos dados sugerem que ambos agonistas alfa-adrenérgicos säo potentes liberadores de GH, podendo ser utilizados na avaliaçäo da reserva hipofisária