Search PubMed⌕ Search

Biomedical subjects

W M Herrmann

Publications and source records attributed to W M Herrmann.

At least 73 records · Page 4Linked to original sources
PubMed1987

COMSTAT rule for vigilance classification based on spontaneous EEG activity.

For the classification of sleep stages, international standards based on visual EEG analysis have been established and are in common use, although we are well aware of their limitations. Several authors have suggested different procedures for classifying the stages of vigilance during the waking stages. No universally accepted paradigm, however, has yet been developed. The proposed vigilance classification procedures are based either on visual or automatic analysis procedures. Even though the EEG activity and patterns that reflect vigilance changes have been identified and described as indicators of the state of alertness, opinion is divided on how these should be combined in a vigilance classification rule. Automatic methods, on the other hand, have up to now used only part of the information available, the relationship of which to vigilance indicators has only been partially explored. The COMSTAT (Dept. of Computation and Statistics, AFB-Arzneimittelforschung, Berlin, FRG) rule combines visual and automatic analysis procedures. Different vigilance-dependent EEG patterns, such as the proportion of occipital background rhythm under resting conditions and its replacement by either faster or slower waves, the frequency range of the occipital rhythm and the anteriorization phenomena, have been used as information for a latent class analysis (LCA5) with 5 classes (stages of vigilance). There is a high correlation between the results of the LCA5 with visual classification rules made by experts. Using a robust discriminant analysis function which takes into account prior probabilities of the classes, and with a linear cost function for misclassification, an automatic rule with power spectrum variables was fitted to the results of the LCA5. Reclassification and split-half classification showed a high overlap between LCA5 and automatic classification. The result of this procedure is a new vigilance classification rule that is based on an objective mathematical rationale for the combination of different vigilance-indicative EEG activities and patterns but which can be applied to power-spectral estimators in an automatic EEG analysis procedure.

Aged↗
PubMed1987

Psychotropic drug profiles: comparisons by topographic maps of absolute power.

In a double-blind fourfold crossover design, 11 subjects were randomly assigned to placebo, 10 mg diazepam, 75 mg amitriptyline, and 75 mg chlorpromazine. During a simple vigilance task, 12 midline and left hemisphere leads were recorded before and 3 h after drug administration. The EEG was quantified by spectrum analysis, the topographic structure displayed by brain mapping techniques, and the results compared with earlier studies which used the same design and drugs. Diazepam showed the expected increase in beta; however, fast beta was increased as much as slow beta. Amitriptyline showed an increase of slow wave power and a reduction of alpha. In contrast to earlier studies, a decrease of fast beta was found. In addition, the spatial pattern of alpha changed from an occipital to a parietal maximum. Chlorpromazine showed an increase in the theta band. In occipital regions, there was a small decrease of fast beta; however, centrally there was an increase of both slow and fast beta. These results were confirmed by a multivariate analysis of variance.

Adult↗
PubMed1987

The analgesic efficacy of flupirtine in comparison to pentazocine and placebo assessed by EEG and subjective pain ratings.

In a placebo-controlled double-blind study the analgesic efficacy of the non-narcotic analgesic flupirtine (80 mg i.v.) was evaluated in comparison with the opioid pentazocine (30 mg i.v.). The variables investigated were the subjects' pain ratings (E), the somatosensory evoked cerebral potentials (SEP), the auditory evoked potentials (AEP) and the power spectral density of the ongoing EEG (PSD). One stimulus block before (PRE) and one stimulus block after (POST) medication were applied. In one stimulus block 80 intracutaneous electrical stimuli of two- and three-fold pain threshold amperage were given in randomized order of intensity and inter-stimulus intervals. Both treatments reduced the subjects' pain ratings significantly, while the placebo values were constant. These effects on pain ratings were in parallel with the SEP changes. The peak-to-peak amplitudes of the late components were significantly diminished by both drugs. Placebo had no effect on this variable. The AEPs remained considerably constant after all three treatments indicating specific drug effect on the pain-related somatosensory pathways. Flupirtine showed effects similar to those of pentazocine in terms of pain relief. The changes in ongoing EEG activity, however, were of a different kind. Pentazocine changed the EEG in an opiate-like manner, while flupirtine increased relative power in the theta and beta range.

Aminopyridines↗
PubMed1987

On the adverse reactions and efficacy of long-term treatment with flupirtine: preliminary results of an ongoing twelve-month study with 200 patients suffering from chronic pain states in arthrosis or arthritis.

In order to investigate the efficacy and safety of long-term treatment with flupirtine in patients with chronic pain, in particular arthrosis and arthritis, a study was planned which, when completed, will encompass the treatment of 200 patients over a 12-month period. The present paper is a preliminary report of this ongoing study. The report deals with 104 patients: 55 of whom completed the 12-month treatment period and a 2-week follow-up phase, during which flupirtine was replaced by placebo in order to be able to detect drug-withdrawal effects. Forty nine patients withdrew from the study. Most of the patients were suffering from degenerative rheumatic arthrosis or inflammatory rheumatic arthritis. The average daily dosage was 300 mg. The incidence of drop-outs was highest in the first months with hardly any patients withdrawing in the last six months. Fifteen patients dropped out because of side effects (dizziness, nausea, sleep disturbances, and headache). Ten patients dropped out because of ineffectiveness, seven because of side effects plus ineffectiveness, and three because of side effects and other reasons. The remaining 14 patients dropped out because of other or non-medical reasons. For the 55 patients who completed the study, the analgesic took effect within 45 minutes to 2 hours, the duration of effect was 4-6 hours. Three-quarters of the patients responded to the drug, one-quarter did not. The analgesic effect remained constant during the 12-month treatment, as did the average number of capsules taken per month. There was no evidence that tolerance developed. The most frequent side effects were drowsiness (9% of patients), dizziness (11%), dry mouth (5%) and pruritus (9%). The withdrawal symptom scale completed every month during treatment (to determine baseline values) and every day throughout the 2-week placebo post-treatment phase showed no changes in the median. The mean value increased during the withdrawal phase, however, indicating that the symptomatology was more pronounced in some subjects. After withdrawal, the non-specific symptoms increased to a greater extent than symptoms from the opiate scale. The symptoms were present throughout the withdrawal phase. If the withdrawal phenomena had corresponded to the flupirtine's terminal half-life, then the symptoms ought to have been present mainly in the first few days. There was a slight trend for lowering systolic blood pressure but no changes in diastolic blood pressure or heart rate, nor changes in the ECG or laboratory analysis that could be related to flupirtine. These preliminary data suggest that flupirtine is safe when given for a period of one year.

Adult↗
PubMed1987

Are nootropics a separate class of drugs? A differentiation in various models.

Psychostimulants, analeptics, and nootropics are three classes of drugs that have been used with varying success in the treatment of impaired brain functions. They all produce an excitatory and disinhibitory effect on the CNS but can be distinguished through their characteristic properties. Psychostimulants are drugs that lead to a general, but nonphysiological activation, which is followed by a phase of inhibition. Analeptics are drugs that stimulate the CNS, in particular the respiratory and circulatory centers, and which in high doses lead to convulsions. Nootropics are drugs that (in impaired brain functions) lead to a physiological activation of adaptation.

Aged↗
PubMed1987

[Effect of lormetazepam, triazolam and flunitrazepam on rapid eye movements, K-complexes and sleep spindles in normal probands].

"Equipotential" doses of lormetazepam, triazolam and flunitrazepam were tested regarding their influence on K-complexes, sleep spindles and rapid eye movements. The receptor affinity was used to determine the equipotency. In this respect triazolam, lormetazepam and flunitrazepam show a relationship of 1:2:4. Lormetazepam, however, showed only slight changes of the three neurophysiological parameters even when given as double dosage. Triazolam and flunitrazepam reduce K-complexes considerably, increase sleep spindles enormously and reduce REM activity markedly; both substances suppress the first REM period, flunitrazepam even the second one. All three of the benzodiazepines have the same effect on the dissociation of K-complexes and sleep spindles; epochs with K-complexes or sleep spindles are favored compared to epochs with K-complexes and sleep spindles. The general reduction of K-complexes and the increase in sleep spindles can be interpreted as a sleep protective function. When deciding on the dosage, however, REM-suppression should be used as a guide since it has the strongest effect on the cyclic structure of sleep which nowadays is considered to be the safest evidence of well balanced sleep behavior.

Adult↗
PubMed1986

Contribution to the search for vigilance-indicative EEG variables. Results of a controlled, double-blind study with pyritinol in elderly patients with symptoms of mental dysfunction.

We used a clinical pharmacological model to test pyritinol versus placebo in patients with mental deficiency and a clinical diagnosis of beginning chronic brain syndrome. Following a two weeks' washout phase, 50 patients were randomly allocated to two treatment groups of 25 patients each, receiving either 200 mg pyritinol three times daily, or placebo under double-blind conditions. The treatment period lasted 8 weeks. To be included in the study, patients had to have at least 50% subvigil phases in the 15-min EEG resting recording. We define such behaviour as a neurophysiological disturbance of vigilance. Scores in the Benton test were to be 2 points below the expected value, and/or the NAF score was to be above a standard value attained in an old peoples' home (greater than or equal to 14). We used this clinical pharmacological model for an internal validation of our Vigilance Index (VI). According to our definition, the Vigilance Index should express vigilance in the sense of an optimalization of the neuronal system to enable this system to perform better. The delta F power and the alpha slow-wave index have been considered as vigilance-indicative variables in the EEG. We believe that vigilance can be better expressed by a multidimensional approach, which takes into account all EEG elements that express vigilance, such as the replacement of the occipital basic rhythm (e.g. alpha or beta rhythm) into slow waves, the lowering of the dominant occipital frequency (be it an alpha or beta frequency), the anteriorization of the basic rhythm in the occipital field to the frontal region.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1986

On the effects of pyritinol on functional deficits of patients with organic mental disorders.

In 120 geriatric patients suffering from cerebral functional disorders with a moderate to rather severe degree of chronic brain syndrome, the effects of pyritinol were investigated in a placebo-controlled, randomized double-blind study. Furthermore, we attempted to find some evidence for the validity of a neurophysiological vigilance model which had already been used earlier. In the previous study it had been possible to show a rise in the vigilance level in patients under pyritinol treatment. The investigation began with a two-week single-blind placebo wash-out phase and continued over a 12-week treatment period, with six weeks' treatment in a hospital ward and six weeks' outpatient treatment (or in a geriatric home within a hospital setting). Pyritinol was administered three times daily in coated tablets each containing 200 mg. The course of the trial was controlled using two rating scales (SCAG, BGP), a physician's Global Impression (GI) and two performance tests (SKT, ZVT-G). There were 13 drop-outs, four because of intercurrent diseases, nine because they did not fulfill the inclusion criteria. The data of 107 patients were included in the statistical analysis, 54 on pyritinol and 53 on placebo. No notable adverse drug reactions were observed that were not similarly reported in the placebo group (Table 1). Statistically significant results were found in favor of pyritinol compared with placebo in both the level of clinical symptomatology (Fig. 1) and the performance level (Fig. 4). Particularly impressive was the superiority of pyritinol in the factor "social behavior" of the SCAG. Considering the clinical relevance of the changes it can be concluded that in both groups improvements occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

Affective Symptoms↗
PubMed1986

Combined pharmaco-EEG and pharmacopsychological study to estimate CNS effects of ketanserin in hypertensive patients.

When developing a new compound, potential side effects on the central nervous system (CNS) should be systematically investigated to determine the drug's safety, e.g., in respect of operating machinery or driving a car. The present study investigated CNS effects of ketanserin, a newly developed S2-serotonergic antagonist, in hypertensive patients. A multidimensional research strategy was used combining pharmaco-EEG and pharmacopsychological methods. The investigation consisted of two separate double-blind, randomized, and placebo-controlled studies, which were, however, planned together and in part included the same patients. The first study was carried out in 2 X 24 patients receiving chronic treatment with 2 X 20 mg ketanserin for 2 weeks, followed by 2 X 40 mg for a further 3 weeks. The second study was performed in 2 X 20 patients after subacute administration of 20 mg twice daily for six days. A multidimensional research strategy was employed to investigate CNS effects on functional and performance measures. Vigilance-related parameters, such as the alpha slow wave index and the absolute delta power, were assessed with pharmaco electroencephalography. Critical flicker-fusion frequency served as a measure of central sedation. Psychomotor performance and concentration tests were used to detect CNS effects which might impair car-driving ability. In addition, subjective well-being and adverse drug reactions were recorded. Ketanserin proved to be a safe drug to lower blood pressure. Only after chronic treatment were there slight indications that ketanserin could have a sedating and inhibiting action on the CNS. However, the differences between placebo and the ketanserin group, and the alterations within each group, were so minimal that they were not considered clinically relevant. A negative effect of ketanserin on car-driving ability is not very likely. The results show that the model was sensitive enough to detect CNS effects with sufficient certainty.

Adult↗
PubMed1986

Pentazocine and flupirtine effects on spontaneous and evoked EEG activity.

Somatosensory (SEP), auditory evoked potentials (AEP) and power spectral density of ongoing EEG (PSD) were investigated under different drug conditions: the opioid pentazocine (30 mg), the centrally acting non-narcotic analgesic flupirtine (80 mg) and placebo were administered i.v. in a double-blind cross-over study (intersession interval 7 days) with 20 healthy male subjects. Intracutaneous electrical stimuli were applied to the finger tip with randomized intensities of two- and threefold individual pain threshold. One stimulus block consisted of 80 trials. Mean values of two stimulus blocks per session were analyzed: one block before and one block 30 min after treatment. Pentazocine significantly reduced the peak-to peak amplitude of the late SEP components (N150-P240) from pretreatment to posttreatment blocks, and flupirtine diminished this amplitude to nearly the same degree. With placebo no substantial reduction was found. In contrast to these drug-induced changes in SEP, the AEP components showed no significant alterations after any treatment. The PSD under pentazocine showed a reduction of total power. This effect was mainly due to a reduced power in the alpha band. The PSD under flupirtine showed slight increases in power of theta, alpha and beta activity. Again, under placebo no changes from pretreatment to posttreatment conditions occurred. The difference in EEG change might suggest different sites of action of the two analgesics.

Aminopyridines↗
PubMed1983

Effect and efficacy - on the function of models for the assessment of therapeutic efficacy.

Whilst the "effect" of a drug can be observed or deduced from observational data, the concept of "therapeutic efficacy" represents mainly a theoretical construction of a high degree of abstraction which is inconceivable without reciprocal combination with other theoretical constructs. The "therapeutic efficacy" of drugs can be investigated only via clinical-pharmacological or clinical models. Several examples are given. The strength of evidence of models is discussed as well as the necessity to continually test them empirically.

Animals↗
PubMed1983

An absolute must in clinico-pharmacological research: pharmaco-electroencephalography, its possibilities and limitations.

During drug development effects on blood cells, metabolism or function of heart and circulation are routinely examined. In case there is evidence of influence on such systems, examinations in clinical pharmacology are done. For the organ central nervous system the same rules should be followed, independently whether a substance is primarily a psychotropic drug or developed for other indications. Besides pharmacopsychological procedures pharmacoelectroencephalography is the most sensitive method to describe drug induced changes on brain function of humans. In event related research (e.g. evoked potentials) it is easier to form hypotheses for the mechanism of reaction after stimulation. About the validity of spontaneous cortical activity, like scalp recorded EEG we have little knowledge. However, a single signal of the spontaneous activity is analyzed into several components, each of which can be influenced differently by various drugs. Important areas of pharmacoelectroencephalography are: 1) Determination of CNS effects on a functional level; judgement whether a pharmacon has a potential for influencing CNS function in comparison to placebo. 2) Characterization of CNS-effects; determination of vigilance changes and classification of the profile in comparison to the EEG-effects of standards. 3) Determination of dose/efficacy and time/efficacy relations; description of kinetic data based on an effect-parameter, in contrast to blood levels; comparison of different galenic formulations; determination of onset and duration of effects; etc. 4) Determination of sleep-wake rhythms; measurement of influence on sleep/waking behaviour in the sleep laboratory or under vigilance controlled conditions during daytime.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain↗
PubMed1983

The COMSTAT algorithm for multimodal factor analysis: an improvement of Tucker's three-mode factor analysis method.

Three-mode factor analysis, as developed by Tucker in 1966, is a method for nonredundant representation of data arrays with three subscripts (e.g. observations classified according to persons by variables by conditions). Tucker , however, did not succeed in obtaining a least-squares solution for his model. We derive in this paper a necessary condition for a least-squares solution and construct an algorithm which improves any given initial solution in the least-squares sense. We show that this algorithm converges to a representation satisfying the necessary conditions for a least-squares solution. The method is in no way restricted to three dimensions, but can be applied to any multimodal data array.

Alpha Rhythm↗
PubMed1983

Example for applying the COMSTAT multimodal factor analysis algorithm to EEG data to describe variance sources.

An example is given for the application of the COMSTAT algorithm for multimodal factor analysis to EEG power spectral data. The COMSTAT algorithm enlarges Tucker 's three-mode factor analysis to a multimodal one, and improves his algorithm by a least squares solution. The EEG power spectral data from 65 healthy subjects with an occipital rhythm between 8 and 12 Hz were taken. For demonstration purposes we selected three modes, which have been used by other authors: mode 1: 29 frequency classes, 1n of relative power, in delta f = 1.0-Hz steps between 1 and 30 Hz; mode 2: 16 segments, 40 s each, during the two situational vigilance conditions reaction time (RT) and resting (RS), and mode 3: 65 persons. The frequency mode could be described sufficiently by five factors which we called: delta F/alpha F1; nu F/alpha F2; beta F1/alpha F1; beta F2; beta F3. The factor-loading profiles were similar to those described earlier in independent data. Thus, in the three-mode model we obtained results comparable to those of two-mode models. In the level of 16 situational segments only two factors were extractable. They described the two situations RT, higher vigilance level, and RS, lower vigilance level. In order to demonstrate the changes in factor structure, if a two-mode model is enlarged by a third mode, we used two models for the description of personal (P) variance. When the matrix persons X segments (P X V) was taken, only two factors were extractable.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1982

Relationship between EEG dynamics and pharmacokinetics of the benzodiazepine lormetazepam.

Clinical experience with benzodiazepines shows that observable effects like sedation do not persist as long as predicted by pharmacokinetic data. As a pharmacodynamic parameter closely related to effects of tranquillizers we used the quantitative pharmaco-EEG to compare time courses of these parameters with plasma level time courses. The subjects received single oral doses (1, 2 and 3 mg) of the benzodiazepine lormetazepam. Plasma levels were detected by radioimmunoassay. After fast absorption dose-dependent plasma level peaks could be determined 2 hours after administration. Applying an open two-compartment body model the drug was excreted with an elimination half-life of 10.3 hours. EEG power reached maximum changes after 1 hour in the delta, theta, alpha 2 and beta 1 frequency bands, as well as in the dominant alpha-frequency, and declined after that with different speeds to previous levels. Three to five hours after drug administration no significant changes could be detected. Vigilance sensitive EEG changes (delta, alpha 2) diminished earlier than indicated by plasma level half-lives. In contrast the decline of relative beta-power parallels plasma level time courses more closely under the 3 mg dose. In the present investigation, the computerized EEG appears to be a suitable indicator of monitoring time courses of sedative effects after single oral doses of benzodiazepines.

Administration, Oral↗
PubMed1982

[Comments on the rules by Rechtschaffen and Kales about the visual scoring of sleep EEG recordings].

The rules by Rechtschaffen and Kales present numerous problems; they sometimes even contradict physiological facts. This is due on the one hand to the manual being limited to central leads only, and on the other hand to rules which are partly too narrow, partly too broad and partly too complex. Furthermore, there are situations and physiological facts for which the manual does not have any rules. The exclusive evaluation of central leads has to result in a different scoring for numerous epoches of stages than an evaluation of leads from all hemisphere electrodes. In addition, frontal or occipital graphoelements such as mitten-pattern and sleep lambda are not even included. It is often difficult to make a distinction between an "alpha-sleep type" and pre-arousals (micro-arousals); the latter also applies to alpha groups in REM sleep. In particular however, if frontal, parietal and occipital leads are included, then the stage 2, above all however stages 3 and 4 will be represented more frequently, as sigma spindles, K-complexes and delta-waves are frequently found in a recognizable form only in the non-central leads. Further difficulties result from different paper speeds of 15 or 10 mm/s and from the rule concerning the allocation from stage 1 to stages 2 or REM.

Electroencephalography↗