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Biomedical subjects

J Krauth

Publications and source records attributed to J Krauth.

At least 19 recordsLinked to original sources

Effects of chronic substance P treatment and intracranial fetal grafts on learning after hippocampal kainic acid lesions.

The purpose of this experiment was to investigate whether the neurokinin substance P (SP) can enhance adaptive graft effects on learning and memory functions in animals with lesions of the hippocampus. Adult male Wistar rats received a bilateral kainic acid (KA) lesion of the dorsal hippocampus. One week postlesion, bilateral grafts of fetal hippocampal tissue suspension were applied into the damaged region in half of the animals, whereas the other half received sham transplants (physiological saline). Animals of the control group received a bilateral sham lesion of the hippocampus and sham transplants. One week after transplantation surgery, the rats were tested in the place version of the Morris water maze over a period of 9 weeks. Then they were tested for SP-induced conditioned place preference and on a step-through inhibitory avoidance task. All animals received IP injections of either SP (5 or 50 micrograms/kg) or the SP vehicle (0.5 ml/kg). The treatment with SP or the vehicle was begun 1 week after transplantation and was performed 5 days a week over a period of 10 weeks. During behavioral tests in the water maze and avoidance task, application of the substances was performed 5 h after testing. For the conditioned place preference test, the conditioning trials were performed immediately after drug administration; the test trials were given 24 h later. Chronic administration of 50 micrograms/kg SP, but not 5 micrograms/ kg SP, was found to improve water maze performance in lesioned animals with and without grafts. Unexpectedly, the lesion group with the graft without additional SP treatment was not superior to the lesion group devoid of the graft in this task. The rats without lesions of the hippocampus still showed a conditioned place preference to 50 micrograms/kg SP after 9 weeks of repeated SP applications. In the inhibitory avoidance task, the grafts facilitated retention performance independent of whether SP treatment was given. The morphological analysis of the transplants revealed higher graft volumes and a higher diameter of large pyramidal neurons (> 10 microns) in rats chronically treated with 50 micrograms/kg SP.

Animals

Single-subject experiments to determine individually differential effects of anxiolytics in generalized anxiety disorder.

In the pharmacotherapy of chronic generalized anxiety disorder (GAD) rationally grounded guidelines on the treatment to choose in individual cases are not evident in the literature. The present study was designed to address this question in 30 patients with chronic GAD. Within a period of 31 weeks amitriptyline 30 mg/day, flupentixole 1.5 mg/day, clotiazepam 15 mg/day and placebo were administered 4 times for 1 week, double-blind and at random to each patient. U tests showed that in 19 patients one agent was superior to the other substances (p < 0.05). There was no significant difference between the drugs in 11 patients. However, a meta-analysis across all single-subject experiments showed that in individual patients suffering from chronic GAD differential effects of anxiolytic agents can be found by means of single-subject experiments (p < 0.001). The findings lend further support to the hypothesis that, in an approach to optimize pharmacological treatment of patients suffering from chronic GAD, single-subject experiments may be useful.

Adult

Parametric analysis of sojourn times in conditioned place preference experiments.

In conditioned place preference experiments, groups of animals are typically compared by means of the total time spent in a treatment environment. The total times are often positively skewed, which prohibits the use of parametric procedures that require normal distributions. Common response time models for such total times are also inadequate because the fit of the models to the data is often poor. The present paper assumes that the sojourn times of a single animal are independent and that they all follow the same 1-parameter exponential model. The exponential parameter allows a number of simple interpretations. We propose point estimates, confidence intervals, a goodness-of-fit test, and a test for comparing 2 samples. The procedures are also applied to single animals, and a test is given for comparing the animals of a group. The kind of parametric analysis suggested enables better interpretation than does the simple distribution-free comparison of 2 groups based on the total time spent in the treatment environment.

Animals

Quantitative analysis of recovery curves.

It is assumed that recovery curves may be produced either by a dynamic process caused by a feedback mechanism or by a linear compensation process which is independent of previous compensation. Based on this assumption, 3 types of recovery functions are derived. Two behavior functions correspond to each of these types of recovery curves, one starting at a low level and the other at a high level. For each of the resulting 6 types of behavior curves, examples of real data have been reported in literature. Elementary parameter estimates are provided and substantial interpretations of the parameters are given. Behavior measures are derived for the data from an illustrative example, and 1 of the 6 behavior curves is fitted to this data. By additionally taking into account a physical repair function which is assumed to cause a certain delay in recovery, it is shown that an even better fit can be achieved.

Animals

Comments on the paper by Möller et al. (1989): problems in single-case evaluation.

Möller et al. (1989) investigated the effects of sleep deprivation on depressive patients using a single-case analysis based on Kleiter's 1986 approach. Here it is discussed why it is so difficult to perform single-case analyses and why Kleiter's approach in particular may lead to wrong interpretations of the data. It is indicated that any kind of single-case analysis is based on assumptions which possibly do not hold and that it is therefore always precarious to base substantial conclusions on this type of analysis.

Bias

The interpretation of significance tests for independent and dependent samples.

The assumptions upon which a correct interpretation of the t-test depends are rarely fulfilled by data from the neurosciences. This applies to both independent and correlated samples. The Mann-Whitney U-test is suggested as an alternative for the t-test for independent samples. The way in which significant results from this test should be interpreted is discussed. The Wilcoxon matched-pairs signed-ranks test is not suggested as an alternative for the t-test for correlated samples, since significant results can occur with this test, even when there are no differences between the distributions of the two samples tested. A modification of the U-test for dependent samples is proposed instead. The use of the latter test, and of the U-test, is illustrated by numerical examples from real data.

Neurophysiology

Methods and problems of prediction.

A review is given of concepts and problems in statistical prediction analysis. First some concepts of prediction (Bayesian, non-Bayesian, time series and others) are introduced. Then in particular prediction by means of multiple linear regression and multiple discrimination is discussed and hints are given with respect to alternative procedures. Various results concerning prediction in time series and by means of contingency tables and cluster analyses are reported.

Bayes Theorem

Nonparametric analysis of response curves.

Many experimental designs in the behavioral sciences and neurosciences yield for each subject a response curve defined by number of correlated measurements. The common parametric and nonparametric statistical tests assume independent measurements and cannot be used in this context. After reviewing contemporary approaches to this problem, procedures for the cases of two independent samples and two matched samples of response curves are proposed. Each curve is approximated by an orthogonal polynomial. In the case of two independent samples the polynomial coefficients are compared by a multivariate median test while in the case of matched samples a multivariate sign test is used. The methods are illustrated by real data sets.

Adult