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Biomedical subjects

S Johannes

Publications and source records attributed to S Johannes.

At least 19 recordsLinked to original sources

Developmental dyslexics show altered allocation of attention in visual classification tasks.

OBJECTIVES: Event-related brain potentials (ERPs) were recorded to investigate allocation of attention in adult developmental dyslexics. SUBJECTS AND METHODS: Twelve adult developmental dyslexics and 12 matched normal controls performed three visual choice reaction tasks. In the passive oddball condition, subjects watched two different simple visual stimuli presented with 87.5 and 12.5% probability. In the active oddball condition, participants responded to the low-probability target stimulus. In the active 50/50-condition, both stimuli were presented with 50% probability and a response was required to the target stimulus only. RESULTS: No group differences emerged for performance, P300 latency or laterality and for N200 amplitude, latency or laterality. An enhancement of P300 amplitude with a frontal distribution was found for NoGo (standard)-stimuli in both active conditions for the dyslexic sample. CONCLUSION: Results are discussed in the context of deviances in allocation of attentional resources in dyslexic readers.

Adult↗

Experimental Escherichia coli epididymitis in rats: a model to assess the outcome of antibiotic treatment.

OBJECTIVE: To assess the effect of initial antimicrobial therapy with a new highly potent quinolone (sparfloxacin) on the outcome of infection, especially acute and chronic inflammation, in a rat model of unilateral Escherichia coli epididymitis. MATERIALS AND METHODS: The study included 60 Sprague-Dawley rats, each of which received 0.1 mL of an E. coli (0:6 strain) suspension (106 colony forming units/mL) injected into the right ductus deferens. At 24 h after infection an oral antimicrobial treatment with sparfloxacin was initiated in half of the animals. The rats were killed 14 days, 3 and 6 months after infection, and both epididymes and the prostate gland cultured to re-isolate E. coli. To evaluate the grade of inflammation in both epididymes, histological variables, including acute and chronic inflammation and scar formation, were evaluated and a total inflammatory score, representing the sum of all variables, computed. RESULTS: Whereas antimicrobial therapy eradicated the pathogen, in untreated animals the pathogen was detectable for up to 6 months after infection in the infected epididymis and/or the prostate gland, while the contralateral epididymis was sterile. The inflammatory reaction in the infected epididymis was significantly less in treated animals (P < 0.001). Subclinical nonbacterial inflammation was present in the contralateral epididymis. CONCLUSIONS: Although adequate antimicrobial treatment eradicated the pathogen and reduced the grade of epididymal damage, inflammation was not avoided. Subclinical inflammation of the contralateral epididymis may contribute to impaired fertility. These results indicate that an inflammatory reaction initiated by bacteria might persist as a nonbacterial process despite early therapy, or by bacteria undetectable by conventional culture techniques, and may compromise male fertility.

Animals↗

Batch potency testing of inactivated erysipelas vaccines by ELISA--development, validation and implementation.

Inactivated erysipelas vaccines are widely used to protect pigs against erysipelas disease caused by the bacterium Erysipelothrix (E.) rhusiopathiae. Quality control tests for this vaccine are laid down in the European Pharmacopoeia (Ph.Eur.) Monograph No. 64. A laboratory animal model using a vaccination-challenge procedure is currently required as batch potency test. More than 10 years ago we initiated the first studies to develop an alternative ELISA potency model to replace this regulatory challenge test in mice. A short retrospective outline of the various steps from the development of the method until implementation into the regulatory requirements is described.

Animal Testing Alternatives↗

Discrepant target detection and action monitoring in obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) has been related to altered mechanisms of action monitoring and target detection, and it has been hypothesized that hyperactive striatal-cortical circuits constitute the underlying pathophysiology. This study used event-related brain potentials (ERPs) to explore this hypothesis. A choice reaction time experiment was carried out in a group of OCD patients and a normal comparison group. The P3b component of the ERP to targets was taken as an indicator of the target-evaluation process and the response-locked error-related negativity (ERN) served as an indicator of action monitoring. We hypothesized that the OCD group would show a shortened P3b latency and an amplitude-enhanced ERN. Consistent with our expectations, the P3b latency was shorter and the ERN amplitude was higher in the OCD group. Unexpectedly, we also observed a prolonged ERN latency in the OCD group and a more posterior topography of this component. The data provide partial support for the hypothesis of a hyperactive neural network in OCD. In addition the disorder must involve pathophysiological processes that are presumably related to other aspects of its complex and heterogeneous clinical hallmarks.

Adult↗

Quality control of inactivated erysipelas vaccines: results of an international collaborative study to establish a new regulatory test.

According to the specifications of the European Pharmacopoeia (Ph. Eur.) monograph (Swine Erysipelas Vaccine (Inactivated), Monograph no. 64, European Pharmacopoeia, 3rd edn., 1997) on erysipelas vaccines for veterinary use, batch potency is estimated in a multi-dilution assay after immunisation and infection of mice. Recently, we described a serological assay system (ELISA) which has the potential to replace this challenge-based model (Beckmann R, Cussler K. Wirksamkeitsprüfung von Rotlaufimpfstoffen an der Labormaus. ELISA kontra Infektionsversuch. ALTEX 1994;Suppl. 1:39-45; Rosskopf-Streicher U, Johannes S, Hausleithner D, Gyra H, Cussler K. Suitability of an ELISA for the batch potency test in laboratory mice. Pharmeuropa BIO 1998;1:65-70). The humoral immune response is quantified in pooled sera of ten mice three weeks after immunisation. The results are expressed as relative potency (RP) in comparison to a reference serum. After a pre-validation study had been performed with success (Rosskopf-Streicher U, Johannes S, Wilhelm M, Gyra H, Cussler K. Potency testing of swine erysipelas vaccines by serology - results of a pre-validation study. ALTEX 1999;16:123-8), we initiated an international collaborative study with five European manufacturers and seven regulatory authorities to validate the assay and model. All participants were provided with blind-coded erysipelas vaccines of different potencies, the ELISA kit and test instructions. The participants had to immunise mice, to prepare serum samples and to perform the ELISA. Inter-laboratory reproducibility was reported by the pass/fail criteria of the vaccines under test. Intra-laboratory precision was assessed by comparing repeated measurements on three consecutive days. Day-to-day variation within the laboratories was statistically analysed by comparing pairs of RPs using Lin's concordance correlation coefficient. The results show that the ELISA is indeed a suitable alternative to replace the vaccination-challenge test. Furthermore, this new model reduces the number of animals required for the potency test by approximately 80%.

Analysis of Variance↗

Central effects of sildenafil (Viagra) on auditory selective attention and verbal recognition memory in humans: a study with event-related brain potentials.

The purpose of this study was to assess possible central side-effects of sildenafil (Viagra) on attention and memory functions. Sildenafil and placebo were administered in young male subjects in a double-blind balanced cross-over design. Behavioral patterns and event-related brain potentials (ERP) were recorded in a spatial auditory attention and a visual word recognition task. While behavioral patterns did not reveal any overt effects of sildenafil, auditory ERPs were indicative of an enhanced ability to focus attention (amplitude enhancement of Nd-effect) and to select relevant target stimuli in the sildenafil condition (P3 component). In the memory task, CNS-effects of sildenafil were evident in a reduction of a negativity in the 150-250 ms range. No overt effects on behavior were observed. Nevertheless, the data reveal CNS-effects of sildenafil necessitating further studies.

Adult↗

Oxazepam alters action monitoring.

RATIONALE: Oxazepam has been demonstrated to slow reaction times and increase the rate of omission errors in attentional experiments. This suggests that action monitoring might also be impaired. OBJECTIVES: The present study used the event-related brain potential (ERP) technique to investigate this hypothesis. The P3b component to targets was taken as an indicator of the target evaluation process, and the response-locked error-related negativity (ERN) served as an indicator of action monitoring. We hypothesized that the amplitudes of ERN and P3b would be reduced as an effect of oxazepam. METHODS: A simple "oddball" reaction time experiment was conducted in a double-blind crossover study of 30 mg oxazepam versus placebo. In order to investigate variations in attentional allocation, separate experimental runs were undertaken with target frequencies of 50% and 80%. RESULTS: ERN and P3b amplitudes were lower in the 80% target condition than in the 50% condition. Oxazepam did not affect behavioral parameters but was associated with an ERN of lower amplitude than the placebo condition. ERN amplitude variations between target conditions remained unchanged. CONCLUSIONS: Although the intake of 30 mg oxazepam did not impair behavioral performance, measures of the electrophysiological recordings show that action monitoring processes were altered. We argue that this may be related to the anxiolytic properties of the drug and may constitute an important causal factor for behavioral impairments after the intake of oxazepam.

Adult↗

Differences in brain potentials to open and closed class words: class and frequency effects.

Closed class (determiners, pronouns, conjunctions, prepositions etc. ) and open class (nouns, verbs, adjectives, adverbs) words have different linguistic functions and have been proposed to be processed by different neural systems. Here, event-related potentials (ERPs) were recorded in young German-speaking subjects while they read closed class and open class words flashed upon a video-screen. In the first experiment closed class words were sorted into four different frequency categories and open class words into three categories. The words were presented in a list with the subjects' task to detect occasional non-words. A centroparietal negativity (N400) with a peak latency of about 400 ms varied in amplitude as a function of frequency in both classes. The N400 in closed class items, however, was considerably smaller than that in open class words of similar frequency. A left anterior negativity (N280/LPN) showed some degree of frequency-sensitivity regardless of word class. Only for the very high frequency closed class words a frontal negativity with an onset of about 400 ms was obtained (N400-700). This N400-700 effect was replicated in the second study, in which medium frequency closed and open class words and very high frequency closed class words were presented at the fifth position of simple German sentences. It is suggested that neither N400 nor the left anterior negativity (N280/LPN) distinguish qualitatively between the two word classes and thus claims about different brain systems involved in the processing of open and closed class words are not substantiated electrophysiologically. The N400-700 effect is possibly related to specific grammatical functions of some closed class items, such as determiners.

Adult↗

Altered inhibition of motor responses in Tourette Syndrome and Obsessive-Compulsive Disorder.

OBJECTIVES: The Gilles de la Tourette Syndrome (TS) and Obsessive Compulsive Disorder (OCD) have been shown to display impaired cognitive and motor inhibition. This study investigated inhibitory mechanisms of motor responses in order to expand the understanding of sensorimotor integration processes in both disorders. We hypothesized that both patient groups would display altered frontal inhibitory activity. MATERIAL AND METHODS: To this end event-related brain potentials (ERPs) were recorded in a STOP-paradigm in groups of TS and OCD patients and in a control group. The paradigm required the execution of a motor response after a "go" signal was given and the occasional suppression of this response after a second "stop" signal occurred. RESULTS: Behavioral parameters and Lateralized Readiness Potential (LRP) confirmed that both patient groups were well able to initiate motor responses. "Go" and "stop" stimuli elicited an enhanced frontal negative activity in both patient groups. In addition, "stop" stimuli were associated with a frontal shift of the NoGo-Anteriorization (NGA) in the TS group but not in the OCD group. CONCLUSIONS: The data are interpreted to indicate altered frontal inhibitory functions. Similarities and dissimilarities between the findings for TS and OCD are discussed with respect to other pathophysiologic aspects of the disorders.

Adolescent↗

Electrophysiological measures and dual-task performance in Tourette syndrome indicate deficient divided attention mechanisms.

Tourette syndrome has been associated with impairments of attentional functions such as distractability, even in subjects without co-morbid attention deficit hyperactivity disorder. Based on the results of earlier research we hypothesized that Tourette syndrome patients might employ altered control mechanisms of attentional processes and have concurrent difficulties in allocating their attentional resources among competing tasks. Event-related brain potentials (ERPs) were recorded in a group of Tourette syndrome patients and in a matched control group during a dual task experiment. This experiment required the simultaneous detection of visual and auditory target stimuli which were manipulated to yield two different difficulty levels each of which were varied orthogonally. The behavioural parameters confirmed the intended performance differences between difficult-to-detect targets and easy-to-detect targets. This was paralleled by lower amplitudes and longer latencies of the corresponding P3b-ERP subcomponents. Although Tourette syndrome patients were unimpaired in overall performance they showed an increased interference of visual task demands with auditory target perception. In parallel they also exhibited a reduced amplitude of the P3b component to auditory targets. The findings show that Tourette syndrome patients are not generally impaired in their dual task performance. The allocation of attentional resources to competing tasks however, is altered. We speculate that this may be related to deficient inhibitory functions.

Adolescent↗

Alterations of cognitive functions induced by exogenous application of thyroid hormones in healthy men: a double-blind cross-over study using event-related brain potentials.

The influence of experimentally induced subclinical hyperthyroidism on cognitive functions was tested using exogenous thyroxine or placebo. In a double-blind cross-over design, 24 healthy young men received either 300 microg of levothyroxine or placebo for two consecutive 3-week periods. Determination of thyrotropin (TSH), total triiodothyronine (T3), thyroxine (T4), and sex hormone binding globulin (SHBG) confirmed the induction of subclinical hyperthyroidism. Three weeks after treatment with placebo or T4, subjects were tested in two visual search tasks, one requiring the serial scanning of a stimulus array of eight items in order to detect a missing feature (serial task), while the other task allowed the parallel processing of eight items in order to detect an extra feature. Reaction times varied greatly between the tasks while no effect of T4 medication was revealed on overt search behavior. The late cognitive components of the event-related brain potentials (ERP) were registered during the tasks using a multichannel recording. The late positive component (P300) to target stimuli showed a significant reduction in amplitude in the parallel search task in hyperthyroidism, while for the serial search task a significant frontal negativity was revealed for target stimuli, both suggesting an increased effort to be exerted for the execution of visual search tasks. Thus, short periods of subclinical hyperthyroidism in the range commonly induced in the treatment of thyroid cancer patients induce distinct alterations in brain-electric activity.

Adult↗

Differential effects of emotional content on event-related potentials in word recognition memory.

The aim of this study was to delineate the influence of the emotional content of stimuli to be remembered on the recognition performance of normal subjects by means of the event-related potential (ERP) technique. When words are presented repeatedly, brain responses to repeated and recognized items are characterized by a more positive waveform, referred to as "old/new effect". Words judged for their emotional connotation ("negative", "positive" and "neutral") were presented successively on a video monitor to subjects, who had the task to indicate whether a given word occurred for the first ("new") or second ("old") time within the list by pressing one of two buttons. For each word category, the ERPs of the old words were more positive compared to those of the new items from about 250 ms after stimulus. The old/new effect was significantly enhanced for the negative and positive items compared to the neutral stimuli between 450 and 650 ms after stimulus pointing to a significant influence of the emotional content of words on verbal memory processes. This paradigm appears to be feasible to investigate interactions of emotion and cognition in psychiatric patients.

Adult↗

Emotion/cognition-coupling in word recognition memory of depressive patients: an event-related potential study.

Depressive patients show deficits in memory functions. However, the underlying mechanisms remain unclear. Experiments with a special emphasis on the link between emotion and cognition appear challenging. The aim of this study is to investigate the influence of the emotional content of words on memory in non-medicated depressive patients (n=11) compared with a control group (n=11) utilizing event-related brain potentials (ERPs). In a continuous word recognition paradigm brain responses to repeated items are characterized by more positive waveforms of ERPs. This recognition effect ('old/new effect') has been shown to be sensitive to parameters relevant for memory processing. For the purpose of this ERP experiment visually presented words were classified into three different categories of emotional content. The ERPs for the correctly detected 'old' (repeated) words showed an increased positivity beginning approximately 250 ms post-stimulus, concurring with a good recognition performance. In addition, old/new effect and behavioral data were sensitive to words' different emotional connotations in the control group. In contrast, the depressive patients performed worse and showed no significant old/new effect. Nevertheless, their recognition performance was also enhanced by the emotional content. Furthermore, a differential effect of the emotional content on frontal ERPs was found between groups. In contrast to the control group, a reduced old/new effect indicates a reduced working memory capacity in the moderately depressed patients. This is suggested to be partially due to changes of the emotion/cognition coupling related to ruminations with preferably negative emotional connotation. However, the emotional content also affects recognition performance in the depressive patients.

Adult↗

Botulinum toxin treatment of cocontractions after birth-related brachial plexus lesions.

The authors studied botulinum toxin type A therapy of severe biceps-triceps cocontractions after nerve regeneration following birth-related brachial plexus lesions. Six children (age, 2 to 4 years) were treated two to three times over a period of 8 to 12 months with 40 mouse units of botulinum toxin at two sites of the triceps muscle. Elbow range of motion improved from 0 to 25 to 50 deg to 0 to 25 to 100 deg (p < 0.05), and muscle force of elbow flexion increased from a mean of Medical Research Council classification 1.7 to 3.7 (p < 0.05). After a 1-year follow-up, there was no clinical recurrence.

Birth Injuries↗

Word recognition memory before and after successful treatment of depression.

One of the most frequent and neuropsychologically well investigated symptoms in depression is reduced memory capacity. In this study, we investigated the course of disease in 16 patients with moderate depression and Borna disease virus (BDV) infection. Recently, it could be shown that BDV infection might play an important role in the etiology of subtypes of depression. Amantadine treatment was used as an antidepressant and antiviral compound. In order to assess memory capacity, event-related potentials (ERPs) were evaluated in ten of sixteen patients in a continuous word recognition experiment using a series of emotionally neutral, positive or negative words. During the treatment period the patients' clinical condition improved significantly. ERPs showed a reduced old/new effect before and after treatment independent of the words' emotional content. These findings suggest a reduced memory capacity being relatively independent of clinical outcome and ability to use emotional connotations for memory mechanisms. However, a significant positive shift over frontal electrodes did occur, which was concomitant with the improvement of depression, suggesting evidence for changed frontal cortical activity.

Adult↗

Changes of laboratory markers of cognitive brain function by thermostimuli in the elderly.

OBJECTIVE: Plain external applications of physical stimuli, which are used quite commonly in geriatric care in Germany, have not been studied for their influence on cognitive brain function. The aim of this randomized crossover study was to examine the influence of dermatoreceptive stimuli on cognitive brain function in healthy geriatric volunteers. METHODS: Twenty-four healthy volunteers (23 women, 1 man) were randomized into two groups (crossover design). Group A (mean age, 68.8+/-6.2 [SD] years) was treated with a 10 degrees C to 12 degrees C cold stimulus for 10 seconds (a so-called "Kneipp face shower"), followed by a cold 10 degrees C to 12 degrees C wetpack at the neck for 1 minute. Group B (mean age, 69.8+/-5.3 [SD] years) was subjected to an identical procedure but with warm to neutral temperatures of 34 degrees C to 36 degrees C. After I week the two groups were interchanged. The parameters of interest were the critical flicker frequency (CFF) and the latencies of the event-related P-300 potentials of the visual evoked potentials (VEP), which can be considered an electroencephalographic marker of the cognitive functional ability. The CFFs and the P-300 latencies and amplitudes were measured directly both before and 10 minutes after the application of the respective stimuli. In addition, the CFFs were recorded 30 and 60 minutes later. RESULTS: After cold water stimuli were applied, the CFF increased from 32.55+/-2.26/sec (mean+/-SD) to 33.06+/-2.25/sec (p = .003) 10 minutes after the stimulus. Thirty minutes later the CFF was still elevated at 32.95+/-2.3/sec (p = .043). The P-300 latencies, after cold water application, decreased by 4.8% (p < .001), from 266.5+/-21.1msec (mean+/-SD) to 253.7+/-16.9msec. After warm stimuli they increased from 258.69+/-14.8msec to 266.17+/-20.1msec (p = .01). The P-300 amplitudes were significantly elevated, by 5% (p = .004), only after cold stimuli. CONCLUSION: Cold water applied locally to the face and neck region can provoke significant changes in electroencephalographic markers as measured by an electroencephalographic marker (VEP and P-300 latency) and, by inference, may help to improve cognitive function in the elderly.

Aged↗