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Biomedical subjects

P Schuster

Publications and source records attributed to P Schuster.

At least 19 recordsLinked to original sources

Mutation in autocatalytic reaction networks. An analysis based on perturbation theory.

A class of kinetic equations describing catalysed and template induced replication, and mutation is introduced. This ODE in its most general form is split into two vector fields, a replication and a mutation field. The mutation field is considered as a perturbation of the replicator equation. The perturbation expansion is a Taylor series in a mutation parameter lambda. First, second and higher order contributions are computed by means of the conventional Rayleigh-Schrödinger approach. Qualitative shift in the positions of rest points and limit cycles on the boundary of the physically meaningful part of concentration space are predicted from flow topologies. The results of the topological analysis are summarized in two theorems which turned out to be useful in applications: the rest point migration theorem (RPM) and the limit cycle migration theorem (LCM). Quantitative expressions for the shifts of rest points are computed directly from the perturbation expansion. The concept is applied to a collection of selected examples from biophysical chemistry and biology.

Catalysis

[Noninvasive studies of the left ventricular systolic function in patients over 65 years old].

Left ventricular functions were assessed in 96 patients (26 men, 70 women aged over 65 years; mean age 74.6 +/- 6.3 years) with various cardiovascular diseases (arterial hypertension, coronary heart disease, cardiomyopathy, various cardiac defects) by comparing various left-ventricular time intervals obtained from resting ECGs, apex cardiograms, carotid-pulse curves and phonocardiograms with left-ventricular ejection fractions by echocardiography. The correlations were strongest with the Weissler index (ratio of pre-ejection and left-ventricular ejection times), PEP/LVET (r = -0.76; P less than 0.001), with PEP itself (r = -0.65; P less than 0.001), as well as with rate-corrected PEP (r = -0.71; P less than 0.001). The plain chest X-ray did not make it possible to assess quantitatively patients with diminished cardiac pump function, despite radiological signs of congestion.

Age Factors

Dynamics of small autocatalytic reaction networks--I. Bifurcations, permanence and exclusion.

Catalysis in replication networks has become an important issue in biophysics and other areas of biology. Examples are RNA catalysis, idiotype recognition in the immune response and dynamical models of Maynard-Smith games in sociobiology. Chemical reaction networks describing catalysed, template-induced reproduction of three species are analysed in full generality. The nine-dimensional parameter space is reduced to three relevant angular coordinates which determine completely the phase portraits (PPs) and the bifurcation patterns. All cases are classified and all generic as well as most of the non-generic transitions are listed and described.

Catalysis

Psychometric assessment of DSM-III personality disorders: another facet of the problem.

An empirical study with the Personality Diagnostic Questionnaire, which in substance follows exactly the criteria of personality disorders described in the DSM-III, is used to highlight a number of problems connected with the DSM-III. Criticisms of the DSM-III previously expressed by other authors, e.g. concerning multiple choice between characteristics and equal weighting of different symptoms, are supported by this empirical study.

Cluster Analysis

[Comments on the diagnostic principles of DSM-III exemplified by the borderline personality disorder].

The first disputes around the DSM-III, which were charged with emotion and cathected by ideologies, are now followed by criticisms based on practical experience with the criteria used in the diagnostic approach of the DSM-III. The present paper is an attempt to show for the area of personality disorders, (and here in particular for borderline personality disorders) that the specific formulation of individual diagnostic questions is a contributory factor to the diagnostic assessment in this field, despite the descriptive approach of the DSM-III. By comparing different item formulations for the same criterion we try to illustrate the problems involved in a purely quantitative registration of characteristics. When criteria, such as identity, interhuman relationship, etc. are concerned, subjective variables will always contribute to the diagnostic assessment.

Borderline Personality Disorder

Error thresholds of replication in finite populations mutation frequencies and the onset of Muller's ratchet.

The occurrence of thresholds for error propagation in asexually replicating populations is investigated by means of a simple birth and death model as well as by numerical simulation. Previous results derived for infinite population sizes are extended to finite populations. Here, replication has to be more accurate than in infinitely large populations because the master sequence can be lost not only by accumulation of errors--similar to the loss of wildtype through the operation of Muller's ratchet--but also by natural fluctuations. An analytical expression is given which allows straight computation of highly accurate values of error thresholds. The error threshold can be expanded in a power series of the reciprocal square root of the population size and thus increases with 1 square root of N in sufficiently large populations.

Computer Simulation

Fixation probabilities for advantageous mutants: a note on multiplication and sampling.

If the average number of gametes produced by the individual is small, as may be the case for haploid organisms, then sampling with and without replacement can lead to considerable differences in the fixation probabilities of mutant alleles. As a function of the population size N, these probabilities converge quickly to the survival probabilities given by branching processes with Poisson or Bernoulli offspring distributions.

Biological Evolution

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

A computer model of evolutionary optimization.

Molecular evolution is viewed as a typical combinatorial optimization problem. We analyse a chemical reaction model which considers RNA replication including correct copying and point mutations together with hydrolytic degradation and the dilution flux of a flow reactor. The corresponding stochastic reaction network is implemented on a computer in order to investigate some basic features of evolutionary optimization dynamics. Characteristic features of real molecular systems are mimicked by folding binary sequences into unknotted two-dimensional structures. Selective values are derived from these molecular 'phenotypes' by an evaluation procedure which assigns numerical values to different elements of the secondary structure. The fitness function obtained thereby contains nontrivial long-range interactions which are typical for real systems. The fitness landscape also reveals quite involved and bizarre local topologies which we consider also representative of polynucleotide replication in actually occurring systems. Optimization operates on an ensemble of sequences via mutation and natural selection. The strategy observed in the simulation experiments is fairly general and resembles closely a heuristic widely applied in operations research areas. Despite the relative smallness of the system--we study 2000 molecules of chain length v = 70 in a typical simulation experiment--features typical for the evolution of real populations are observed as there are error thresholds for replication, evolutionary steps and quasistationary sequence distributions. The relative importance of selectively neutral or almost neutral variants is discussed quantitatively. Four characteristic ensemble properties, entropy of the distribution, ensemble correlation, mean Hamming distance and diversity of the population, are computed and checked for their sensitivity in recording major optimization events during the simulation.

Base Sequence

Placebo-controlled study of lisinopril in congestive heart failure: a multicentre study.

A double-blind randomised, parallel, placebo-controlled study was performed in patients with congestive heart failure, at 13 centres in 10 countries, to assess the efficacy and safety of lisinopril, a new angiotensin-converting enzyme inhibitor. After a 2-week run-in period, 130 patients receiving digoxin and/or diuretics were randomised to 12 weeks of treatment with lisinopril 5 mg daily (87 patients) or with placebo (43 patients), with an option to increase lisinopril dosage to 10 or 20 mg. Patients treated with lisinopril improved significantly more than placebo-treated patients (p less than 0.05) for all clinical parameters except oedema and paroxysmal nocturnal dyspnoea. Left ventricular ejection fraction rose by 8% in lisinopril patients compared to 2% in the placebo group, while the cardiothoracic ratio and echocardiographic end systolic diameter fell in the lisinopril group (p less than 0.01) but not in the placebo group. Exercise duration was greater in the lisinopril group at all timepoints, and the increase in exercise duration at 12 weeks was greater by more than 2 min in the lisinopril group as compared to the placebo group (p less than 0.01). Changes in clinical and noninvasive parameters such as the New York Heart Association status, were well correlated with changes in exercise duration. Four patients in the lisinopril group and three in the placebo group died in this study, and there were 31 adverse clinical experiences in the 87 lisinopril-treated patients compared to 13 in the 43 placebo-treated patients. We conclude that lisinopril in doses of 2.5-20 mg/day is well tolerated and effective in patients with heart failure who are receiving digitalis and diuretics.

Adolescent

[Angular synthesis in upper tibial valgus osteotomy in osteoarthritis. Apropos of a series of 544 cases].

Five hundred and forty-four valgus osteotomies for medial compartment osteoarthritis of the knee have been performed by two teams working separately over a period of twenty years between 1964 and 1984. From this series the results of a technique which aims to combine precision of correction with stability of fixation have been assessed. The clinical results in the short and medium term are encouraging. Above all, it seems that improvement in the osteoarthritis can be maintained for ten years or more, that is to say greater than the mean expectation of life of the patients.

Adult

A flow system for the study of shear forces upon cultured endothelial cells.

A parallel plate chamber in a flow system has been designed to study the effects of fluid shear stresses on cells. The system was applied to the study of cultured endothelial cells grown on cover slips which were accommodated in recessed wells in the base plate. Dye injection studies in the chamber indicated laminar flow over the cells. Shear rates measured over the cover slips by an electrochemical technique were found to be linear with flow rate. Laser doppler anemometry showed parabolic profiles between the plates. Endothelial cells subjected to flow showed a correlation between the time required for orientation and the magnitude of the shear stress.

Biomechanical Phenomena

Mood-dependent learning. I. Endogenomorphic and psychoreactive depressions--influence of positive and negative feedback on expectancy shifts.

Influenced by Seligman's definition of 'learned helplessness' we studied the change of expectancy after positive and negative reinforcement before the onset and in the course of treatment of endogenomorphic and psychoreactive depressions. Before the onset of treatment patients do not exhibit any systematic change of expectancy after positive or negative reinforcement, in the course of treatment reaction to reinforcement is demonstrable, the type of treatment administered during the observation period causes differences in behavior.

Achievement

Results of learning experiments in the course of treatment of endogenomorphic depression. A comparison of electroconvulsive and pharmacological treatment.

In this study we attempted to break down short-term effects of electroconvulsive therapy (ECT) on memory into anterograde and retrograde amnesia, and for the latter we again separated short-term store performances from those connected with the long-term store of memory. Our experiments included complicated learning tasks. Although impairment caused by ECT was demonstrable in all three test fields, complicated conditioning experiments stored in the long-term store proved to be most sensitive to the disturbing effect of ECT.

Adult