Biomedical subjects

L Linzmayer

Publications and source records attributed to L Linzmayer.

At least 37 records · Page 2Linked to original sources

PubMed1995

Isoflurane narcotherapy in depressive patients refractory to conventional antidepressant drug treatment. A double-blind comparison with electroconvulsive treatment.

This is the first report on a controlled study comparing the therapeutic and non-therapeutic (side) effects of electroconvulsive treatment (ECT) and isoflurane narcotherapy (ISONAR; deep anesthesias with the inhalation of anesthetic isoflurane) in drug-refractory, severely depressed women, who had been randomly allocated either to ECT (n = 10) or ISONAR (n = 10). Patients from each group were subjected to a total of six treatment sessions (two sessions per week) and maintained on a fixed antidepressant drug dose. The antidepressant efficacy of either treatment was evaluated for each treatment session (in search of a 'rapid antidepressant effect') and at weekly intervals. Cognitive functions or signs of an organic brain syndrome were evaluated by means of psychological tests and extensive EEG analyses. Rapid antidepressant effects of the first treatment session were only significant in patients on ISONAR; in the subsequent treatment sessions, ECT also induced rapid antidepressant effects. Antidepressant effects during the treatment period were comparable, and patients on ISONAR improved further during follow-up, whereas patients on ECT tended to relapse. ISONAR-treated patients improved in most psychometric variables, whereas patients on ECT deteriorated. Finally, the EEG patterns of the ISONAR-treated patients remained normal or augmented (dominant alpha power), whereas patients on ECT developed an increase in abnormalities in EEG patterns and theta/delta power. This indicates an organic brain syndrome in patients on ECT.

Adult↗

PubMed1995

Double-blind, placebo-controlled, pharmacokinetic and -dynamic studies with 2 new formulations of piracetam (infusion and sirup) under hypoxia in man.

In a double-blind, placebo-controlled study, pharmacokinetics and pharmacodynamics of 12 g piracetam in 2 different formulations were investigated utilizing blood gas analysis, EEG mapping and psychometry under a transient, reversible, hypoxic hypoxidosis. The latter was induced by a fixed gas combination of 9.8% oxygen (O2) and 90.2% nitrogen (N2, found in 6,000 m altitude), which was inhaled for 23 minutes under normobraic conditions by 18 healthy volunteers. They received after an adaptation session randomized at weekly intervals 12 g piracetam i.v. (250 ml infusion over 30 minutes), 12 g piracetam p.o. (60 ml sirup) and placebo. Blood levels were determined by means of an HPLC at the hours 0, 1, 2, 4, 6, 8 and 24. The 2 formulations showed a very similar time-course, with slightly higher blood levels in the 1st hour after the intravenous than oral administration, and vice versa thereafter. The elimination half-life was 4.3 hours for both formulations, the area under the curve and the clearance value were also almost identical. Evaluation of blood gases, EEG mapping and psychometry were carried out at 0, 2, 4, 6 and 8 hours post-drug. Blood gas analysis demonstrated a drop in SaO2 from 99 to 73 and 70%, in PO2 from 100 to 35 and 33 mmHg, in PCO2 from 36 to 31 and 31 mmHg in the 14th and 23rd minute of inhalation, respectively. pH increased from 7.43 to 7.48 in the respective minutes, while base excess and standard bicarbonate remained stable. EEG mapping exhibited under hypoxia a marked increase of total power, mostly due to an augmentation of delta/theta, and a decrease of alpha activity, which reflects deterioration of vigilance. Both piracetam preparations significantly attenuated this vigilance decrement, with 12 g piracetam i.v. showing its encephalotropic peak effects in the earlier hours, 12 g piracetam sirup in the later hours. At the behavioral level, hypoxic hypoxidosis induced a deterioration of the noo- and thymopsyche, which was mitigated by both piracetam preparations, mostly in the 6th hour. Both formulations were well tolerated.

Administration, Oral↗

PubMed1995

Acute central effects of the calcium channel blocker and antiglutamatergic drug caroverine. Double-blind, placebo-controlled, EEG mapping and psychometric studies after intravenous and oral administration.

In a double-blind, placebo-controlled study, the effects of caroverine (CAS 23465-76-1, Spasmium)--a quinoxaline derived from isoquinoline, the basic structure of papaverine, originally developed as a spasmolytic drug which may, however, exert central effects due to an unspecific calcium channel blocking action and glutamate antagonism--were investigated utilizing EEG-mapping, psychometric and psychophysiological measures. Fifteen healthy volunteers (8 males and 7 females), aged 20-35 years, received randomized and at weekly intervals 40 and 80 mg caroverine intravenously, 40 and 80 mg caroverine orally, as well as placebo. EEG recordings, psychometric and psychophysiological tests, as well as evaluation of pulse, blood pressure and side-effects were carried out at 0, 1, 2, 4, 6 and 8 h. Multivariate analysis of EEG mapping data demonstrated that caroverine exerted a significant action on human brain function, as compared with placebo, at all given dosages, as early as in the 1st and as late as in the 8th hour after both intravenous and oral administration during resting (R-EEG) and vigilance-controlled recording (V-EEG). Subsequent univariate analyses revealed, however, differential effects of caroverine--dependent on recording conditions and doses. In the resting condition, an increase of absolute and relative delta and theta power, a decrease of alpha and beta power and a slowing of the centroid of the delta and theta activity occurred, reflecting sedative action. The latter was slightly time- and dose-dependent (more sedation in earlier hours after higher doses). However, in the vigilance-controlled EEG, a dose-dependent decrease of delta and theta power, an increase of alpha power and an acceleration of the centroid of the delta and theta suggested vigilance-promoting effects, which were more pronounced in the later than earlier hours. Psychometric investigations confirmed these differential central effects. In regard to the noopsyche, an improvement was noted 6 h after the lowest oral dose. In the thymopsyche, a deterioration occurred after all doses except the highest oral dose, suggesting sedation. The latter was also seen after all active compounds as a trend in psychophysiological variables. The drug was well tolerated.

Administration, Oral↗

PubMed1995

[Assessment of experimentally-induced pain effects and their elimination by hypnosis using pupillometry studies].

Hypnotherapeutical technique were often used for control of pain. However, an objective examination of this phenomenon was seldom carried out. The aim of the study was the psychophysiological objectivation of the effect of experimental induced pain and the elimination of pain by means of hypnosis. 22 healthy volunteers (11 female and 11 male) aged between 22 and 35 years participated in the study. In the 1st phase of the experiment static pupillometry was carried out before randomized presentation of a light stimulus (143 lux, 0.3 sec) and of a pain stimulus (coldness-spray, -50 degrees C, 0.5 sec) respectively. Afterwards the dynamic pupillary measurement was done. Additionally the Fourier analyses of pupillary oscillations reflecting central nervous activation during the static measurement (25,6 sec) was calculated. In the 2nd phase the subjects were investigated by means of the same techniques during hypnosis with specific suggestions for elimination of pain. Under light condition as well as after induction of pain an autonomic deactivation could be observed during hypnosis. Furthermore under pain condition a central deactivation could also be found, reflecting the depth of the hypnosis and the reduced perception of pain.

Adult↗

PubMed1995

[A new method for testing the psychopharmacologic pupil oscillation hypothesis following administration of a nootropic substance].

Recently a new, precise and economical method for measuring central nervous activation in psychopathological groups was presented. By means of this procedure, the ¿psychopharmacological pupillary oscillations hypothesis¿ after administration of the nootropic compound bifemelane (CAS 90293-01-9) was examined in oder to assess pharmacologically induced changes in central activation. Before calculating the Fourier analysis, blinks have to be identified and eliminated by means of a new technique, which is called ¿smoothing¿. After application of bifemelane, a marked improvement of symptoms caused by cerebro-vascular disorders was reported. 18 subjects (7 females and 11 males), aged between 60 and 80 years, with a neurological and psychic age-adequate state, from whom a written, informed consent was obtained, participated voluntarily in the study. A placebo-controlled and double-blind design were administered in an interval of 8 days in cross-over design. The study, which also included measurement of noopsychic and thymopsychic changes, was carried out before and in the 2nd, 4th, 6th and 8th hour after application of the substances. In the slow frequency band, after application of bifemelane, an increase of activation (higher amplitudes) could be observed, which lasted from the 2nd to the 4th hour. However, differences between bifemelane and placebo did not reach the level of statistical significance. In faster frequencies, a reduction of the height of the amplitudes was found. Regarding the total spectrum, in the 2nd hour a moderate increase of activation could be demonstrated.

Aged↗

PubMed1994

Pharmacokinetic and -dynamic studies with a new anxiolytic, suriclone, utilizing EEG mapping and psychometry.

1. In a double-blind, placebo-controlled, cross-over study, acute pharmacokinetic, neurophysiological and psychotropic effects of suriclone, a new cyclopyrrolone derivative, were investigated and compared with alprazolam. 2. Fifteen normal young volunteers received randomized oral single doses of placebo, 0.1, 0.2 and 0.4 mg suriclone as well as 1 mg alprazolam as reference compound. Investigations were carried out before and 1, 2, 4, 6 and 8 h after drug administration. 3. Pharmacokinetic investigations by radioimmunoassay showed a dose-dependent fast rise of plasma concentrations with a peak at 1 h and a rapid decline thereafter. Both the Cmax and the AUC values exhibited a linear relationship to dose. 4. EEG brain mapping demonstrated significant CNS effects of both compounds, characteristic for tranquillizers (increase of beta, decrease of alpha and increase of delta activity; attenuation of total power and acceleration of the centroid, i.e. centre of gravity frequency). When compared with alprazolam, suriclone exerted less sedative effects. 5. Time-efficacy calculations showed the pharmacodynamic peak effect of suriclone from the 2nd to the 4th hour, and of alprazolam in the 1st hour. Dose-efficacy calculations showed that the most pronounced CNS changes occurred after 1 mg alprazolam, followed by 0.4, 0.2 and 0.1 mg suriclone. 6. Psychometric investigations demonstrated no significant effects after the two lower doses of suriclone, while 0.4 mg and 1 mg alprazolam induced a decrement both in noopsychic and thymopsychic variables seen after higher doses of anxiolytic sedatives. Psychophysiology (critical flicker fusion, pupillometry, and skin conductance measures) pulse rate, systolic and diastolic blood pressure remained unchanged. 7. Psychophysiology (critical flicker fusion, pupillometry and skin conductance measures) showed differential dose-dependent effects. Pulse rate, systolic and diastolic blood pressure remained unchanged. Anxiolytic-characteristic side-effects (tiredness, drowsiness, etc.) occurred predominantly after the highest doses 0.4 mg suriclone and 1 mg alprazolam.

Administration, Oral↗

PubMed1994

[A new method for measuring central activation: fourier analysis of pupillary oscillations in depressed patients].

While the changes in pupillary size during wakefulness and drowsiness are easy to understand, the origin of pupillary oscillations is quite mysterious. Waves of spontaneous pupillary constriction and dilation accompany periods of increasing sleepiness and spontaneous arousal. Lowenstein et al. (1963) demonstrated that in the dark, the pupils of young normal alert subjects show waves of dilatation and contraction lasting from about 4 to 40 s and measuring up to 0.5 mm. Furthermore, superimposed fast and very extensive oscillations were observed. The first described oscillations seemed to reflect central nervous activation. Therefore we analysed pupillary oscillations during the recording period of static pupillometry (described by the authors in 1992) which lasted for 25.6 s. Before calculating the Fourier analysis, blinks have to be identified and eliminated by means of a new technique which is called "smoothing". Using the Fourier analysis, the spectrum was divided into 5 frequency bands (0.0-0.2; 0.21-0.4; 0.41-0.60; 0.61-0.8; 0.81-1 Hz). We were also interested in the total spectrum. In order to demonstrate utilisation of the new technique, 146 male and female depressed patients (ICD-Diagnosis 296.1, 296.3, 296.1, 296.3 + 300, respectively, 300.4, 301.1, 296.1, 296.3 + 290, respectively), aged between 18 and 45 years, were investigated by means of pupillometry, followed by analysis of pupillary oscillations. The whole group of depressive patients who received antidepressive medication was compared with 64 healthy subjects of similar age to demonstrate differences in the frequency bands.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1993

The effect of biologically-active light on the noo- and thymopsyche and on psychophysiological variables in healthy volunteers.

The study was carried out to show how bright light affects intellectual mnestic performance alertness, mood and psychophysiological variables in order to understand the mechanism of bright light which is still unclear. 15 healthy normal volunteers (8 males, 7 females) aged 22-34 years (mean 27) participated in the study. Exposure to bright light (2500 lux) or dim light (500 lux) was intermittent for 4 h between 9 a.m. and 5 p.m. Psychometric investigations for assessment of noopsychic variables, such as attention and concentration on the one hand, and thymopsychic variables, such as drive, on the other hand, as well as flexibility and psychophysiological measurements were carried out before, as well as 1, 2, 4, 6 and 8 h after baseline. As compared to the dim-light condition, subjects who were exposed to biologically-active light showed an improvement of noopsyche in the 6th and 8th hour. Also, the subjective thymopsyche revealed an improvement lasting for the whole investigation period. Psychophysiological measurements reflected an improvement of central and autonomous activation, which was parallel to the improvement of cognition and of well-being. However, biologically-active light did not affect flexibility.

Adult↗

PubMed1993

Clinical-pharmacological study with the two isomers (d-, l-) of fenfluramine and its comparison with chlorpromazine and d-amphetamine: psychometric and psychophysiological evaluation.

In a double-blind, placebo-controlled, crossover study, the single oral dose effects of 15, 30 mg d- and 30 mg l-fenfluramine (FEN) on psychometric and psychophysiological variables were investigated and compared with those of 50 mg chlorpromazine (CPZ) and 20 mg d-amphetamine (AMPH). Eighteen healthy young volunteers randomly (latin square) received at weekly intervals the 6 different treatments. Noopsychic, thymopsychic, psychophysiological and flexibility evaluations were carried out at 0, 2, 4, 6 and 8 h after drug administration. Either dose of d- or l-FEN induced only minimal noopsychic and thymopsychic changes. In contrast, 50 mg CPZ produced highly significant deterioration in attention, concentration, reaction time, psychomotor activity and complex reaction, as well as subjective deactivation, while 20 mg d-AMPH produced subjective activation. Critical flicker frequency was only decreased by 50 mg CPZ and increased by 20 mg d-AMPH. In regard to pupillary measurements, 15, 30 mg d-, 30 mg l-FEN and 20 mg d-AMPH produced opposite changes (widening of pupillary diameter) to those observed after 50 mg CPZ (narrowing of pupil size). Flexibility remained unchanged after FEN treatments, while it consistently decreased after both 50 mg CPZ and 20 mg d-AMPH. Time- and dose/treatment efficacy relations based on discriminant analysis (centroids) of changes in all variables showed 50 mg CPZ as the most psychoactive drug inducing significant changes from the 2nd until the 8th h, followed by 20 mg d-AMPH inducing significant changes from the 4th until the 8th h, but with opposite signs, while FEN treatments exerted only slight effects between the 2nd to 8th h postdrug.

Adult↗

PubMed1992

Dose-response studies with co-dergocrine mesylate under hypoxia utilizing EEG mapping and psychometry.

In a double-blind, placebo-controlled trial, human brain function and mental performance were studied under two different degrees of hypoxia after administration of two different doses (6 mg and 9 mg) of co-dergocrine mesylate (CDM) utilizing blood gas analysis, EEG mapping and psychometry. Hypoxic hypoxidosis (i.e. impairment of cerebral metabolism due to hypoxia) was experimentally induced by a fixed gas combination of 9.8% oxygen (O2) and 90.2% nitrogen (N2) (found in 6000 m altitude), and of 8.6% O2, 91.4% N2 (found in 7000 m altitude), which was inhaled for 23 min under normobaric conditions by 18 healthy volunteers. They received randomized after an adaptation session placebo, 6 mg and 9 mg co-dergocrine mesylate (CDM). Evaluation of blood gases, brain mapping and psychometry was carried out at 0, 2, 4, 6, 8 h after oral drug administration. Blood gas analysis demonstrated a drop in PO2 to 42 and 32 mm Hg 23 min after inhalation of the 9.8% and 8.6% gas mixture, respectively, PCO2 decreased to 32 and 31 mm Hg, pH increased to 7.46 and 7.47 and base excess increased to 0.50 and 0.90 nmol/l, respectively. EEG mapping demonstrated an increase in delta and decrease of alpha power and a slowing of the centroid over almost the whole brain. 6 mg and slightly less so 9 mg CDM attenuated this deterioration of vigilance (i.e. dynamic state of the neuronal network determining adaptive behavior). At the behavioral level, moderate hypoxia induced a deterioration of noopsychic performance, which was mitigated by 6 mg, but not by 9 mg CDM. A deepening of the hypoxia resulted in a loss of these brain protective effects of both doses. Decrement of the thymopsyche increased after both doses in the moderate hypoxic condition, while under marked hypoxia 6 mg CDM attenuated and 9 mg aggravated this deterioration. Time-wise, brain protective effects reached the level of statistical difference between the 2nd and the 6th hour. Somatic complaints like feeling dazed, giddiness and headache were mitigated dose dependently by CDM in the moderate, but not in the marked hypoxic hypoxidosis.

Adult↗

PubMed1992

Neuropsychological findings and psychiatric symptoms in HIV-1 infected and noninfected drug users.

Reports available on the extent and incidence of cognitive deficits in human immunodeficiency virus (HIV-1) patients are variable. To assess the influence of drug abuse and psychiatric symptoms on the extent of the cognitive deficit, we examined 42 drug-addicted HIV-1 patients and compared them with a group of seronegative drug addicts (n = 31) as well as with a group of healthy controls (n = 50), using a psychometric test battery and standardized psychiatric scales. We found no significant difference in the extent and incidence of cognitive deficits in the group of HIV-1 patients as compared with the seronegative drug addicts. Both groups, however, differed from the normal population group. Remarkable depressive symptoms were found in the HIV-1 infected patient group. We assume that long-term drug abuse contributes markedly to the cognitive deficit of HIV-1 patients, which is further influenced by depressive symptoms.

AIDS Dementia Complex↗

PubMed1992

[Noopsychological changes and psychopathological characteristics of HIV-1 patients of various risk groups].

Reports on neuropsychological assessment and psychopathological symptoms in HIV-1 patients are rather different. The aim of the study was to assess frequency and extent of noopsychic changes and psychopathological symptoms in HIV-1 patients of different risk groups. Of the 77 patients being included in the study 35 patients belonged to risk group 1, 42 to risk group 2. The patient groups were compared to a control-group of healthy volunteers (n = 50) and to a control-group of HIV-negative i.v. drug-addicts (n = 31). The psychometric test battery included Raven and MWT Test, Benton Test, numerical memory Test, ARG Test. Personality variables were assessed by MMPI, Psychopathology by AMDP-System, Hamilton Depression Scale, Wellbeing Scale (von Zerssen), STAI 1 and 2 and BPRS. Patients of risk group 1 showed significantly less impairment of noopsychic performance than patients of risk group 2. Risk group 1 showed only in the Benton Test significant impairment compared to healthy volunteers while risk group 2 in most of the tests was impaired. Risk group 2 did not show impairment compared to the control-group of seronegative drug users. Depressive syndromes mainly in risk group 2 showed a significant influence on the noopsychic performance.

AIDS Dementia Complex↗

PubMed1992

Pharmacodynamics of venlafaxine evaluated by EEG brain mapping, psychometry and psychophysiology.

1. In a double-blind, placebo-controlled study the effects of venlafaxine--a novel nontricyclic compound inhibiting neuronal uptake of serotonin, noradrenaline and to a lesser extent dopamine--were investigated utilizing EEG brain mapping, psychometric and psychophysiological measures. 2. Sixteen healthy volunteers (eight males, eight females) aged 21-36 years received randomized and at weekly intervals single oral doses of placebo, 12.5 mg, 25 mg and 50 mg venlafaxine. EEG recordings, psychometric and psychophysiological tests, and evaluation of pulse, blood pressure and side-effects were carried out at 0, 2, 4, 6, and 8 h. 3. EEG brain mapping demonstrated that venlafaxine exerted a significant action on human brain function as compared with placebo at all three doses, characterized mostly by attenuation of absolute power, increase of relative delta/theta and beta, and decrease of alpha power, as well as by an acceleration of the total centroid fronto-temporally and by its slowing centrally and parietally. These findings are similar to antidepressants such as imipramine. Topographically, drug-induced alterations were most pronounced over both fronto-temporal and the right temporal to temporo-occipital regions. 4. Psychometric and psychophysiological investigations demonstrated significant dose-dependent psychotropic properties of the drug. Multivariate statistics exhibited an improvement of both the noopsyche (e.g. attention, concentration, attention variability, memory, fine motor activity, reaction time performance) and thymopsyche (e.g. drive, wakefulness)) but also significant psychophysiological activation (e.g. in c.f.f., pupillary and skin conductance measures). 5. Time-efficiency calculations showed significant central effects from the 2nd hour onwards, with increasing differences between placebo and treatment up to the 8th hour. Nausea was the most frequent complaint and appeared dose dependent.

Adult↗

PubMed1992

Pupillometry in clinical psychophysiological diagnostics: methodology and proposals for application in psychiatry.

The change in pupillary reactions may be considered as an important parameter of the autonomic nervous system. By means of pupillometry, it became possible to measure both objectively and economically these reactions. The method of microprocessor-assisted "static" and light evoked "dynamic" pupillometry is demonstrated. A high reliability for the static variable of pupillometry was also evaluated. Variables measured during "static and dynamic" pupillometry were factor-analyzed. Four factors (static, dynamic, stimulus specific and restitution dependent) were obtained regardless of whether investigations were carried out in normals or in psychiatric patients. Examples of utilization of pupillometry in psychopharmacology and mental disorders are also described in this essay.

Adult↗

PubMed1991

Psychophysiological reactions in methadone maintenance patients do not correlate with methadone plasma levels.

In methadone maintenance therapy methadone plasma concentrations of 400 ng/ml are necessary to suppress any further opiate action and to provide stabilized maintenance. In a controlled study we have searched for a differentiation in autonomous activation between patients having low and high methadone plasma levels, using static and dynamic pupillometry and habituation of skin conductance response. Results show that there is no difference in psychophysiological response between patients with high (greater than 400 ng/ml) or low (less than 400 ng/ml) plasma levels of methadone. This indicates that there is no reduction in behavioral arousal in patients with high plasma methadone levels. On the basis of these findings, there is no rationale to maintain patients on plasma levels below 400 ng/ml.

Adult↗

PubMed1991

Comparison between observer assessment and self rating of withdrawal distress during opiate detoxification.

The Subjective Opiate Withdrawal Questionnaire (SOWQ) and the Objective Opiate Withdrawal Scale (OOWS) were administered to detect withdrawal distress during a rapid opiate detoxification. No correlations could be observed between the clinical assessments and self ratings of the 20 patients participating in this study. The observers' ratings of withdrawal reached pre-treatment levels within 3 days. In subjective rating, withdrawal distress returned to normal levels 120 h after detoxification. We conclude, that self reports are as important as observer ratings in assessing treatment efficacy. The use of both scales might prevent early relapse after detoxification.

Adult↗

PubMed1991

Combined naloxone/methadone preparations for opiate substitution therapy.

Every opportunity should be used to reduce the risk of HIV-1 infection and transmission among intravenous drug users (IVDUs). Methadone maintenance is widely accepted to keep the drug user away from risk-laden practices and to stop intravenous drug use. In order to minimize the diversion and intravenous abuse of methadone in maintenance programs, the effects of a combined naloxone/methadone preparation through oral intake and the effects of an intravenous administration were tested. In opiate addicts, the intravenous administration of this mixture caused a severe withdrawal syndrome lasting for 15 to 30 minutes. The oral administration of this combination was indistinguishable from methadone alone. It is argued that this combination therapy prevents the intravenous abuse of methadone in maintenance programs.

Administration, Oral↗

PubMed1991

Similar efficacy of abrupt and gradual opiate detoxification.

A study comparing abrupt and gradual opiate detoxification which identified the efficacy by means of computer-assisted pupilometry and rating of withdrawal distress is presented. This paper concentrates on the efficacies of these two detoxification modes with regard to the identical results after successful opiate detoxification treatment. The findings of the present investigation support the hypothesis that withdrawal distress returns to a normal level after rapid naloxone withdrawal treatment within 6 days. Similar results can be seen for inpatient methadone withdrawal after 3 weeks of treatment. These results indicate that by rapid detoxification therapy, the time of withdrawal can be effectively shortened. Considering the low dropout rate and the high degree of acceptance during rapid detoxification, the rapid detoxification regimen is an effective and economic alternative to gradual withdrawal treatments.

Adult↗