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Biomedical subjects

P Anderer

Publications and source records attributed to P Anderer.

At least 91 records · Page 5Linked to original sources

EEG-brain mapping in schizophrenics with predominantly positive and negative symptoms. Comparative studies with remoxipride/haloperidol.

EEG brain maps obtained in 48 drug-free hospitalized schizophrenics diagnosed according to DSMIII demonstrated significant differences as compared with normal controls characterized by a decrease of alpha-1 activity, increase of beta activity and acceleration of the centroid. These findings suggest a state of sustained hyperarousal in schizophrenia. While the patients with negative schizophrenia showed a bi-temporal and frontal augmentation of delta/theta activity, patients with florid symptomatology exhibited just the opposite findings. Alpha-1 activity was attenuated, beta activity augmented in both groups with the findings more pronounced in the positive schizophrenia group. The increase of slow activity suggests an organic factor in the pathogenesis of the negative syndrome, which was supported by correlation maps between EEG measures and the apathy syndrome as measured by the AMDP system. Treatment of schizophrenics with predominantly positive symptoms with 2 different neuroleptics such as remoxipride and haloperidol resulted also in differential effects on brain activity: while haloperidol augmented delta/theta and alpha activity and decreased beta activity, remoxipride produced a decrease of slow and increase of beta activity as well as an acceleration of the centroid suggesting vigilance-promoting properties of the drug. These differential effects on the neurophysiological level were also reflected at the behavioural one evaluated by psychometry, while global clinical evaluation showed, as expected, similar improvement with both drugs (apart from extrapyramidal side effects being significantly more pronounced after haloperidol than remoxipride). Our findings suggest that brain electrical signal topography is a promising method in regard to a better understanding of pathogenesis and treatment in schizophrenia.

Adult↗

Sleep laboratory studies on single dose effects of suriclone.

1. In a double-blind, placebo-controlled sleep laboratory study single doses of suriclone, a new non-benzodiazepine anxiolytic binding to benzodiazepine receptors, were investigated with respect to sleep and awakening. 2. Sixteen healthy young volunteers spent 10 nights in the sleep laboratory: 1 adaptation night, 1 baseline night and 4 drug nights (placebo; 0.2 mg, 0.4 mg suriclone; 2 mg lorazepam as reference drug) and 4 subsequent wash-out nights (drug-interval: 1 week). Somnopolygraphic investigations (22.30 h to 06.00 h) were commenced 0.5 h after drug-intake. A self-rating scale for sleep and awakening quality as well as psychometric tests were completed in the morning. 3. Hypnotic effects were most pronounced after lorazepam in regard to total sleep time and sleep efficiency. After lorazepam as well as after 0.4 mg suriclone nocturnal awakenings decreased significantly as compared with placebo, which was reflected in an improved subjective sleep quality after both dosages. Suriclone 0.2 mg did not induce any alterations in all night sleep. 4. In the morning, well-being, drowsiness and reaction time performance deteriorated after lorazepam as compared with placebo but not after suriclone. The latter was significantly superior to lorazepam with respect to subjective awakening quality, well-being, emotional rapport, drowsiness and attention. 5. Blood pressure and pulse remained unchanged after all of the drugs. Critical flicker frequency and muscle strength decreased only after lorazepam as compared with placebo.

Adult↗

Smooth pursuit eye movements in schizophrenia: influences of neuroleptic treatment and the question of specificity.

The authors investigated smooth pursuit eye movements (SPEMs) in 66 schizophrenic and 40 major affective patients and 39 healthy controls. The results showed significant differences of both patient groups as compared to the controls. Schizophrenics with neuroleptic treatment in the preceding 2 years were significantly more disturbed than the controls, the affective patients and the untreated schizophrenics. Acute neuroleptic medication and neuroleptic treatment of a duration of 4-6 weeks appear not to significantly influence the quality of SPEMs.

Adolescent↗

Differential effects of a new central adrenergic agonist--modafinil--and D-amphetamine on sleep and early morning behaviour in young healthy volunteers.

Modafinil (CRL 40476) is a recently developed central alpha adrenergic agonist with vigilance-promoting properties. In a double-blind, placebo-controlled sleep laboratory study, its single-dose effects on objectively and subjectively evaluated sleep, morning awakening, and early morning behaviour were investigated and compared with amphetamine. Ten young healthy volunteers of both sexes spent 12 nights in the sleep laboratory: one adaptation night, one baseline night, five drug nights (100 mg and 200 mg modafinil; 10 mg and 20 mg d-amphetamine; placebo) and five subsequent washout nights. The drugs were administered in one week intervals according to a Latin square design. Somnopolygraphic investigations were performed between 22h30 and 06h00. Subjects received the drug orally half an hour before bedtime. A self-rating scale for sleep and awakening quality and early morning behavior was completed subsequent to the morning toilet. Thereafter, noopsychic and thymopsychic variables were evaluated utilizing a psychometric test-battery. Statistical analyses of objective sleep variables demonstrated that modafinil causes no significant changes as compared to a placebo. Sleep initiation remained unchanged after all of the drugs, while sleep maintenance was impaired dose-dependently after d-amphetamine. Thus, total sleep time and sleep efficiency decreased significantly after 20 mg d-amphetamine as compared to the placebo and modafinil. In regard to sleep architecture a reduction of sleep stage 2 and rapid eye movement-sleep occurred under d-amphetamine while modafinil did not exhibit such an effect. Subjective sleep quality was significantly better after modafinil than after the reference compound. Subjective awakening quality and well-being in the morning did not show any significant findings. Furthermore, no differences were observed between the placebo and the other drugs concerning objective awakening quality (evaluated by psychometric tests). Critical flicker frequency increased significantly after 20 mg d-amphetamine as compared to the placebo. Pulse rate and evening and morning blood pressure remained unchanged. These data stress the necessity to differentiate between "vigility-increasing" properties of amphetamine and "vigilance-promoting" properties of modafinil.

Adult↗

Differential effects of the new central adrenergic agonist modafinil and d-amphetamine on sleep and early morning behaviour in elderlies.

Modafinil (CRL 40476) is a new central alpha-adrenergic agonist with vigilance-promoting properties. In a double-blind, placebo-controlled sleep laboratory study its single-dose effects on sleep and early morning behaviour were investigated and compared with d-amphetamine. Ten elderly healthy volunteers (mean age: 68 years) spent 12 nights in the sleep laboratory: one adaptation night, one baseline night, five drug nights (100 mg and 200 mg modafinil; 10 mg and 20 mg d-amphetamine; placebo) and five subsequent washout nights. The drugs were administered orally in one week intervals at 10:00 p.m., and all-night somnopolygraphic investigations were performed between 10:30 p.m. and 6:00 a.m. A self-rating scale for sleep and awakening quality as well as psychometric tests were completed in the morning. d-amphetamine caused a dose-dependent impairment of sleep maintenance and sleep architecture, while modafinil did not. Thus, a significant reduction of total sleep time, REM-sleep and sleep stage 2 was seen after d-amphetamine when compared to placebo and 100 mg modafinil. Corresponding with these objective results, subjective sleep quality deteriorated significantly only after 20 mg d-amphetamine as compared to placebo. Morning investigations revealed an increase of CFF after 20 mg d-amphetamine. Pulse rate, evening and morning blood pressure remained unchanged. These findings suggest a different mode of action of the two compounds.

Aged↗

Psychophysiological research in psychiatry and neuropsychopharmacology. I. Methodological aspects of the Viennese Psychophysiological Test-System (VPTS).

In order to find a psychophysiological paradigm for clinical application we have developed the Viennese Psychophysiological Test-System (VPTS), which includes a special selection and combination of experimental situations, physiological measurements, behavioral measurements and data analysis. This study presents detailed information concerning these four aspects. Experimental situations are related to the human model of information processing, where short changes of stimulus-reaction-correlated processes are selected: resting conditions (eyes open, eyes closed), habituation-orienting test, psychomotor-performance test, signal-detection test and reaction-time test. Physiological measures include central and peripheral activity of the cerebrospinal and autonomic nervous system: cortical activity (spontaneous electroencephalogram, auditory evoked potentials, late positive components, slow potentials), ocular activity (eye and eyelid movements), electrodermal activity (skin conductance), cardiac activity (heart rate measurement), respiratory activity (rate of respiration) and peripheral vascular activity (finger pulse volume). Behavioral measurements extend from micro behavior to complex diagnostic systems: psychomotor measurements, self-reported mood, arousal and visceral perception, psychological and psychiatric interviews. The application of this test system in 15 elderly subjects of both sexes aged 58-77 years gives information which exceeds the sum of the singular constructing elements of the VPTS.

Electrocardiography↗

Psychophysiological research in psychiatry and neuropsychopharmacology. II. The investigation of antihypoxidotic/nootropic drugs (tenilsetam and co-dergocrine-mesylate) in elderlies with the Viennese Psychophysiological Test-System (VPTS).

In a double-blind placebo-controlled study, the effects of tenilsetam, a novel antihypoxidotic/nootropic agent, on spontaneous and event-related activity of the central and autonomous nervous system were studied in 15 elderly subjects of both sexes aged 58-77 years by means of the Viennese Psychophysiological Test-System (VPTS). The VPTS includes a special selection and combination of experimental situations, physiological measurements, behavioral measurements and data analysis. At weekly intervals, the subjects received randomized single oral doses of placebo, 150 mg, 300 mg and 900 mg tenilsetam (TEN) and 5 mg co-dergocrine-mesylate (CDM) as reference drug. Psychophysiological testings were carried out before and 2 h after drug administration. Evaluation of the spontaneous EEG-activity demonstrated no significant drug effects as compared to placebo. In contrast, TEN showed a dose-dependent augmentation of the N1-P2 and N2-P300 amplitudes of the event-related potentials (ERPs) in specific experimental conditions. In reference to placebo, the increase of N2-P300 amplitude after the highest dosage of TEN, as well as after CDM, amounted to approximately 5 microV, which confirms the hypothesis that nootropic drugs may influence the P300 amplitude in the sense of an improved availability of cognitive processing resources. There was no effect on ERP latencies, on mean amplitudes of contingent negative variation and of post-imperative negative variation, on autonomous nervous system, on psychological measurements, nor on reaction time. However, specific improvements were observed in psychomotor measures, such as synchronization accuracy and rhythmicity. These findings highlight the importance of using EEG and ERP measures in different experimental situations in conjunction with behavioral, psychological and autonomous nervous system measures to study nootropic drug effects.

Aged↗

Double-blind, placebo-controlled quantitative EEG and psychometric studies in elderlies on vigilance-promoting effects of an almitrine/raubasine combination (Duxil).

In a double-blind, placebo-controlled study the encephalotropic and psychotropic properties of an acutely and 3-weeks subacutely administered novel drug Duxil (consisting of 30 mg of the antihypoxic almitrine which increases the oxygenation of the arterial blood by specific action on the pulmonary exchange system and of 10 mg raubasine, which potentiates this effect via increase in peripheral circulation), were investigated in 12 elderly subjects in their 70s. Each subject had a treatment of 3 weeks with Duxil and placebo (1 tablet b.i.d.) with an interval of 1 week in between (the order of drug sequence was randomized). EEG recordings, psychometric and psychophysiological tests as well as evaluation of pulse, blood pressure and side effects were carried out at 0, 2, 4, 6 and 8 h after the administration of one single dose on day 1 (acute effect), at the 0 h on day 21 (subacute effect) as well as at the 2, 4, 6, and 8 h after one additional superimposed dosage on day 21 (superimposed effect). Computer-assisted spectral analysis of the EEG demonstrated after single doses of two tablets of Duxil only subtle changes in the resting EEG, while after subacute administration and even more so after one superimposed dosage highly significant changes were observed, which were characterized by an increase of total power, alpha and alpha-adjacent beta activity, decrease in fast beta activity, and by an augmentation of absolute and relative power of the dominant frequency. These findings are indicative of an improvement in vigilance. The latter was seen also at the behavioral level, as psychometric tests showed specifically in noopsychic variables a significant improvement in intellectual, mnestic and psychomotor performance after the novel antihypoxic compound, as compared with placebo. There were practically no changes in thymopsychic variables. Evaluation of psychophysiological variables and side effects showed extremely good tolerability of the drug.

Aged↗

Comparative bioavailability studies with a new mixed-micelles solution of diazepam utilizing radioreceptor assay, psychometry and EEG brain mapping.

In a double-blind, placebo-controlled study the pharmacokinetic and pharmacodynamic properties of a standard solution of diazepam (DZ) (ValiumR) were compared with those of a novel diazepam mixed-micelles solution (DZ MM) (Valium MMR) both after i.v. and i.m. application utilizing radioreceptor assay, quantitative pharmaco-EEG and brain mapping techniques as well as psychometric and psychophysiological methods. The local tolerance was studied as well. The subjects received randomized and, in weekly intervals, following injections: (1) 10 mg DZ i.v. + placebo i.m.; (2) 10 mg DZ MM i.v. + placebo i.m.; (3) placebo i.v. + 10 mg DZ i.m.; (4) placebo i.v. + 10 mg DZ MM i.m.; (5) placebo i.v. + placebo i.m. Blood sampling, EEG-recordings, psychometric and psychophysiological tests as well as tolerance evaluations were carried out at 0, 1/2, 1, 2, 4, 6 and 8 h. Blood level evaluation demonstrated after i.m. application a significantly shortened tmax, a higher Cmax and generally higher plasma concentrations in the first and second hour following the mixed-micelles solution than the standard formulation, which suggests better absorption of the former than the latter in the muscle. Subsequent to i.v. administration, lower blood levels were observed between 30 min and 2 h after DZ MM than DZ. Power spectral density analysis of the EEG resulted in typical anxiolytic-sedative pharmaco-EEG profiles after all 4 active substances as compared with placebo. However, there were significant inter-drug differences as far as topographic aspects (pharmaco-EEG maps) were concerned. DZ MM i.v. induced significantly more initial but also late delta augmentation, alpha attenuation and centroid slowing than DZ i.v. which suggests more sedative effects at those times. Following i.m. application, a significantly more pronounced delta/theta attenuation, beta augmentation and centroid acceleration after DZ MM than DZ suggested more anxiolytic effects of the novel than the standard formulation. Discriminant analysis of changes in 6 thymopsychic, 12 noopsychic and 17 psychophysiological variables demonstrated the best discrimination of the 4 substances based on thymopsychic effects. Considering the latter, all 4 active compounds differed significantly from placebo, with no inter-drug differences after i.v. application but a marked superiority of the novel mixed-micelles solution over the standard solution after i.m. application. Specifically, DZ MM i.m. induced more desactivation and affect-attenuation than DZ i.m.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Topographic brain mapping of EEG before and after open-heart surgery.

The brain function of 60 patients undergoing open-heart surgery (36 patients receiving coronary artery bypass, 21 patients valve replacements, 3 both) was investigated before and 10 days after the operation utilizing topographic brain mapping of the electroencephalogram (EEG). The postoperative EEG changes were characterized by a slight delta-theta increase, an alpha decrease [especially in the fast alpha (10.5-13 Hz) band] and a beta increase in the relative power. The total power and the absolute power of the delta-theta, alpha and beta showed a decrease, the dominant frequency a significant slowing from 9.7 to 9.3 Hz. The centroid of alpha and beta activity decreased as well. These results are similar to findings obtained in patients with organic brain syndrome. The EEG changes were prominent over the left hemisphere, which may be of particular clinical relevance.

Adult↗

Contralateral eye movements and alpha reactivity of lithium patients in recognition tasks.

For the purpose of analyzing memory deficits in patients on lithium therapy the Psychological Labor (E. Opgenoorth et al.) and Lithium Department (R. Wolf et al.) studied not only psychological performance but also biosignals of elementary complexity (characteristic values of eye movements as a reaction to simple light stimuli) and of higher complexity, i.e. those which accompany the cognitive processing of information. Recall and recognition performance for incidentally learned word and picture items was tested in 14 patients receiving lithium treatment. Simultaneously registered EEG (O1-Cz and O2-Cz) and lateral eye movements (LEM) were analyzed with reference to different stimuli. Absolute alpha power and relative event-related desynchronization (ERD) show differences in EEG reactivity between healthy individuals and lithium patients demonstrated by differences in the amplitudes. LEM are characterized by a slight delay of the peaks.

Adult↗

Comparative placebo-controlled pharmacodynamic studies with zotepine and clozapine utilizing pharmaco-EEG and psychometry.

In a double-blind, placebo-controlled study the encephalotropic and psychotropic properties of zotepine - a new tricyclic dibenzothiepine with antidopaminergic, adrenolytic and antiserotoninergic properties - were investigated utilizing quantitative EEG, psychometric and psychophysiological tests as well as clinical observations. Fifteen normal volunteers received randomized (latin square design) and at weekly intervals single oral doses of placebo, 25 mg, 50 mg and 100 mg zotepine as well as 50 mg clozapine as reference compound. Plasma samplings for blood levels, EEG recordings, and evaluation of blood pressure, pulse rate and side-effects were carried out at the hours 0, 1, 2, 4, 6 and 8, while psychometric data were recorded at the same time except the first hour. Computer-assisted spectral analysis of the EEG demonstrated after all three doses significant changes as compared with placebo characterized by an augmentation of delta and theta activity, decreased of alpha and beta activity, slowing of the centroid of the total activity and alpha activity, and decrease of the dominant frequency and its absolute and relative power. Such changes are typical for low-potency basic neuroleptics of the sedative type such as chlorpromazine. Clozapine also augmented slow activities, decreased alpha activity, the dominant frequency and the alpha centroid, but induced in contrast to zotepine a concomitant increase of fast beta activity, acceleration of the beta centroid and no slowing of the dominant frequency, while the total power was significantly attenuated. These findings confirm earlier reports about the pharmaco-EEG profile of clozapine, which has a resemblance to profiles of anticholinergic antidepressants of the amitriptyline type. Psychometric tests demonstrated after the higher doses of zotepine and clozapine a deterioration of noopsychic and thymospsychic functions which was more pronounced after the reference compound than after zotepine. The lowest dose of zotepine, 25 mg, even produced an improvement in numerical memory and complex reaction. CFF, skin conductance, pupillary diameter and pupillary response measurements decreased after both compounds. Dose-efficacy calculations showed 100 mg zotepine and clozapine to be the most CNS-effective compounds, followed by 50 mg and 25 mg zotepine, while placebo induced the least changes. Time-efficacy calculations showed neurophysiological and behavioral peak effects after zotepine at the 4th and 6th hour, as compared with the 2nd and 4th hour after clozapine. Pulse rate increased with both compounds; blood pressure decreased after clozapine but remained unchanged after zotepine.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Topographic brain mapping of EEG in neuropsychopharmacology--Part II. Clinical applications (pharmaco EEG imaging).

Multi-lead analysis of drug-induced changes in human brain function as monitored by the scalp-recorded electroencephalogram (EEG) and subsequent imaging of topographic pharmaco-EEG maps has become possible and practical with the advent of modern mini- and micro-computers. The present paper gives a survey about topographic analyses of pharmaco-EEG data obtained in systematic double-blind, placebo-controlled studies in normal healthy volunteers involving representative drugs of 5 different psychopharmacological classes, such as neuroleptics (chlorprothixene), antidepressants (imipramine), tranquilizers (diazepam), psychostimulants (caffeine), and antihypoxidotics/nootropics (pyritinol). The determination of cerebral bioavailability utilizing time- and dose-efficacy relations, as well as the evaluation of bioequipotency of different formulations of compounds is shown. Topographic pharmaco-EEG seems not only to confirm our previous knowledge that quantitative analysis of the human EEG in combination with certain statistical procedures ("quantitative pharmaco-EEG") is a valuable method to determine if, how, when and at which dosage a drug will be centrally effective, but also to have the potential to show effects of psychotropic drugs on the target organ--the human brain--which could not be previously picked up by single lead recordings. Topographic pharmaco-EEG imaging can be viewed as an enlargement of our armamentarium to better understand the mode of action of psychotropic drugs in human neuropsychopharmacology, as well as to monitor and (eventually) predict therapeutic efficacy in patients.

Adult↗

Short-term sleep laboratory studies with cinolazepam in situational insomnia induced by traffic noise.

In a double-blind, placebo-controlled sleep-laboratory study the short-term effects of cinolazepam--a recently introduced 1,4 benzodiazepine with a half-life of 9 h--on the all-night sleep, morning awakening and early morning behaviour were investigated in 20 young normal subjects, whose sleep was experimentally disturbed by nocturnal traffic noise. The latter was prerecorded on tape and reproduced by loud speakers throughout the night with a sound pressure level of 68-90 dB(A) (energy equivalent mean noise level LAeq: 79dB(A)). According to the parallel group design subjects received either a placebo or 40 mg cinolazepam. Specifically, they spent nine nights in the sleep laboratory: two adaptation nights, one baseline night on placebo, three drug or placebo nights, and three post-drug/placebo nights under traffic noise. Somnopolygraphic investigations were carried out between 22h30 and 06h00. The drug was given orally half an hour before bedtime. Each 30 sec epoch was scored according to the criteria of Rechtschaffen and Kales. In the morning the subjects were awakened by 1000 Hz tones which were increased in loudness in 10 dB steps in two minute intervals. A sleep self-rating scale for sleep and awakening quality was completed half an hour after the morning toilet. Thereafter noopsychic and thymopsychic variables were evaluated utilizing a psychometric test battery. Statistical analyses of objective sleep variables demonstrated a significant improvement of sleep maintenance after 40 mg cinolazepam as reflected by an increase of sleep efficiency, decrease of wake time (during total sleep period) and number of awakenings as compared with the placebo. Sleep architecture was only affected slightly: sleep stage S1 decreased, S2 increased, while S3, S4 and SREM (S rapid eye movement) remained unchanged. Subjective sleep quality improved significantly as well. In the mornings there were no hangover signs, neither in subjective nor in objective psychometric and psychophysiological variables. Finally, the study suggests that man can adapt subjectively to nocturnal traffic noise over one week, although the improvement of objective sleep variables over time did not reach the level of statistical significance.

Adult↗

Topographic brain mapping of EEG in neuropsychopharmacology--Part I. Methodological aspects.

Topographic brain mapping of the electroencephalogram (EEG) is a promising new method in neuropsychiatry and neuropsychopharmacology. Rapid advances in computer technology allow on-line analysis by means of micro-computers. This paper describes an acquisition and signal analysis system for studying neurophysiological and neuropsychopharmacological aspects of human brain function. It consists of a server micro-computer functioning as an acquisition unit which is connected to a workstation micro-computer for statistical analysis and subsequent documentation of data on a printer and color plotter. According to the recommendations for standardization of data acquisition and signal analysis in pharmaco-electroencephalography, the paper mediates detailed information concerning recording and analysis equipment with special emphasis on the treatment of artifacts. Since up to now there is no normative consensus on the choice of reference conventions and interpolation algorithms, the system is designed for high flexibility to enable empirical comparisons between different methods.

Brain↗