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Biomedical subjects

R Dengler

Publications and source records attributed to R Dengler.

At least 55 records · Page 3Linked to original sources
PubMed2001

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↗
PubMed2001

Structural requirements for voltage-dependent block of muscle sodium channels by phenol derivatives.

We have studied the effects of four different phenol derivatives, with methyl and halogen substituents, on heterologously expressed human skeletal muscle sodium channels, in order to find structural determinants of blocking potency. All compounds blocked skeletal muscle sodium channels in a concentration-dependent manner. The methylated phenol 3-methylphenol and the halogenated phenol 4-chlorophenol blocked sodium currents on depolarization from -100 mV to 0 mV with IC(50) values of 2161 and 666 microM respectively. Methylation of the halogenated compound further increased potency, reducing the IC(50) to 268 microM in 2-methyl-4-chlorophenol and to 150 microM in 3,5-dimethyl-4-chlorophenol. Membrane depolarization before the test depolarization increased sodium channel blockade. When depolarizations were started from -70 mV or when a 2.5 s prepulse was introduced before the test pulse inducing slow inactivation, the IC(50) was reduced more than 3 fold in all compounds. The values of K(D) for the fast-inactivated state derived from drug-induced shifts in steady-state availability curves were 14 microM for 3,5-dimethyl-4-chlorophenol, 19 microM for 2-methyl-4-chlorophenol, 26 microM for 4-chlorophenol and 115 microM for 3-methylphenol. All compounds accelerated the current decay during depolarization and slowed recovery from fast inactivation. No relevant frequency-dependent block after depolarizing pulses applied at 10, 50 and 100 Hz was detected for any of the compounds. All the phenol derivatives that we examined are effective blockers of skeletal muscle sodium channels, especially in conditions that are associated with membrane depolarization. Blocking potency is increased by halogenation and by methylation with increasing numbers of methyl groups.

Cell Line↗
PubMed2001

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↗
PubMed2001

Coping strategies in episodic and chronic tension-type headache.

OBJECTIVE: To study the importance of coping with illness strategies in tension-type headache (TTH). BACKGROUND: The pathophysiology of TTH is complex, and coping with illness strategies might contribute to the transformation to a chronic form. METHODS: We examined 89 subjects (mean age, 45.6 +/- 14.8 years; range, 18 to 72 years) with episodic (n = 37) and chronic (n = 52) TTH. Patients were required to fill in a Freiburg Questionnaire of Coping with Illness (FQCI), a von Zerssen Depression Scale, quality-of-life questionnaires, and a headache home diary (over 4 weeks). In addition, pressure pain thresholds (temporal muscles) and total tenderness scores were obtained. RESULTS: Patients with chronic TTH exhibited poorer quality-of-life measures, slightly more depressive symptoms, and significantly stronger avoidance behavior and endurance strategies on FQCI scales F4 and F5 (P< .05). There was no difference between episodic and chronic TTH with respect to measures of muscle tenderness or pain thresholds. CONCLUSIONS: We conclude that disadvantageous coping with illness strategies might contribute to a transformation to chronic TTH.

Adaptation, Psychological↗
PubMed2001

Propofol blocks human skeletal muscle sodium channels in a voltage-dependent manner.

UNLABELLED: Propofol decreases muscle tone in the absence of neuromuscular blocking drugs. This effect probably cannot be attributed solely to central nervous depression. We studied the effects of propofol on heterologously expressed skeletal muscle sodium channels. Our hypothesis was that the decrease in muscle tone may partly be attributed to an interaction of propofol with sarcolemmal sodium channels. Cells were voltage clamped and whole-cell sodium inward currents were recorded in the absence and presence of propofol. When depolarizing pulses to 0 mV were started from a holding potential close to the normal resting potential of muscle (-70 mV), or when a 2.5-s prepulse inducing slow inactivation was applied before the test pulse at -100 mV, a significant reduction in the peak current amplitude was achieved by 10 and 5 microM propofol, respectively (P < 0.001). Half-maximum blocking concentrations with these protocols were 23 and 22 microM. Blocking potency increased at depolarized membrane potentials with the fraction of inactivated channels; the estimated dissociation constant K(d) from the inactivated state was 4.6 microM. These results suggest that propofol significantly blocks sarcolemmal sodium channels at clinically relevant concentrations while maintaining potentials close to the physiological resting potential. IMPLICATIONS: Voltage-gated sodium channels mediate the initiation and propagation of action potentials along the sarcolemma. Results from our study show that those channels are targeted and blocked in a concentration- and voltage-dependent manner by propofol. This mechanism may contribute to the reduction in muscle excitability.

Action Potentials↗
PubMed2001

Unusual presentation of a primary spinal Burkitt's lymphoma.

Primary CNS lymphomas are detected with increasing frequency in immunocompetent and immunodeficient persons. Primary involvement of the spinal roots has only rarely been reported. The unusual history is described of a patient with a primary spinal Burkitt's lymphoma initially presenting as an S1 syndrome showing lymphocytic pleocytosis in the CSF, leading to the misdiagnosis of meningoradiculitis. Repeated spinal MRI disclosed a spinal mass lesion and histological and immunohistological examination of the tumour confirmed the diagnosis of spinal Burkitt's lymphoma.

Adult↗
PubMed2001

Neutralizing botulinum toxin type a antibodies: clinical observations in patients with cervical dystonia.

Neutralization of antibodies poses a problem for a substantial number of cervical dystonia (CD) patients treated with botulinum toxin type A (BoNT/A). Presence of these antibodies may lead to a secondary nonresponse to BoNT/A treatment. In this study, we compared 6 antibody-positive (Ab+) with 12 antibody- negative (Ab-) CD patients treated with BoNT/A (Dysport) and matched for du- ration of treatment, number of BoNT/A injections, and severity of clinical symptoms. The two groups differed in cumulative BoNT/A dose (Ab+, 5984 mouse units [MU ], SD = 3151 MU; Ab-, 3143 MU, SD =1294 MU; P <.05), in addition, ab+ patients were significantly younger (ab+ mean age = 41.3 y, sd =5.9 y; ab - mean age = 56.8 y, sd = 15.3 y; p <.05), in or- der to avoid formation of neutralizing antibodies, doses of bont/a should be kept as low as possible, the risk of antibody formation seems to be higher in younger patients.

Adult↗
PubMed2001

Effect of conditioning transcranial stimulation on motor evoked potentials.

Motor evoked potentials (MEPs) were recorded from extensor carpi radialis muscle in response to paired transcranial magnetic stimuli (interstimulus intervals (ISI) of 3 and 13 ms) with a test stimulus intensity of 120%. The intensity of the subthreshold conditioning stimulus ranged from 55% to 85% of the motor threshold. The threshold of intracortical inhibition (ICI: ISI--3 ms) was significantly lower than the threshold of intracortical facilitation (ICF: ISI--13 ms). The values of test MEP area at 3 ms ISI showed U-shaped dependence on the conditioning intensity while the values of test MEP area at 13 ms ISI recorded over the ICF threshold were augmented with increasing conditioning intensities. The changes of MEP latencies were polyphasic and in one and the same direction for ISIs of 3 and 13 ms. The results are suggesting a simultaneous action of ICF and ICI mechanisms.

Adult↗
PubMed2001

Is tremor an inherent feature of an intact but misadjusted motor control system?

Coordination of voluntary discrete motor responses with ongoing background activity like tremor is investigated for the single-muscle multiple-task condition by experimental and theoretical work. It is shown that the periodic background activity entrains the discrete responses. The experimental results are described by a model of the motor execution stage, and several possible consequences of the model for the motor behavior in Parkinsonian tremor patients are discussed.

Humans↗
PubMed2000

High frequency repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex in schizophrenic patients.

Repetitive transcranial magnetic stimulation (rTMS) has been tried therapeutically in major depression. In order to investigate the therapeutic efficacy of rTMS in psychotic patients, 12 participants (four women, eight men) with schizophrenia according to DSM-IV criteria, aged 25 to 63 years (mean (+/-s.d) 40.4+/-11.0), were enrolled in the study. Following a double-blind crossover design, patients were treated at random with 2 weeks of daily left prefrontal rTMS (20 2s 20 Hz stimulations at 80% motor threshold over 20 min, dorsolateral preforntal cortex) and 2 weeks of sham stimulation. The Brief Psychiatric Rating Scale decreased under active rTMS (p <0.05), whereas depressive symptoms (BDI) and anxiety (STAI) did not change significantly. Prefrontal rTMS might be effective in the non-pharmacological treatment of psychotic patients.

Adult↗
PubMed2000

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↗
PubMed2000

Subthreshold prefrontal repetitive transcranial magnetic stimulation reduces motor cortex excitability.

The prefrontal cortex plays an important role in central motor control. We have examined whether prefrontal repetitive transcranial magnetic stimulation (rTMS) induces changes of motor cortex excitability determined by motor evoked potentials (MEPs) following single-pulse TMS. We studied 18 healthy volunteers stimulated at 5 Hz with 10% subthreshold prefrontal vs. occipital rTMS for 12 s. MEPs from the flexor carpi radialis muscle after single-pulse vertex stimulation were recorded during rTMS at 0, 4, 8, and 12 s. MEP areas decreased significantly after 8 s of prefrontal rTMS (P < 0. 05) but not after occipital rTMS. We conclude that rTMS of the prefrontal cortex may inhibit the primary motor areas.

Adult↗
PubMed2000

Dopamine transporter binding in Gilles de la Tourette syndrome.

Preliminary studies in patients with Gilles de la Tourette syndrome (TS) provided evidence of presynaptic dopaminergic dysfunction, demonstrating increased reuptake sites. Therefore we investigated striatal dopamine transporter binding in 12 TS patients and 9 control subjects using single photon emission computed tomography and 123I-labeled 2beta-carbomethoxy-3beta-(4-iodophenyl)tropane. In TS patients we found significantly higher relative striatal activity ratios (mean +/- SD 12.33 +/- 3.58) than in controls (9.36 +/- 1.35, P< 0.05). Only five patients, however, showed striatum/occipital cortex ratios more than 2 SD above the normal means. Seven patients had activity ratios within the average ratio of the control group plus 2 SD. Regarding the relationship between clinical parameters and striatum/occipital cortex ratios, we found an association between binding ratios and "self-injurious behavior" and "lack of impulse control." This study corroborates previous data suggesting an involvement of the dopaminergic system in TS pathology. Our results demonstrate that an increase in dopamine transporter capacity is a possible but not a necessary alteration, and which appears more likely when self-injurious behavior and lack of impulse control are associated.

Adult↗
PubMed2000

The discontinuous nature of motor execution. I. A model concept for single-muscle multiple-task coordination.

Human movement control requires adequate coordination of different movements, which is particularly important when different motor tasks are simultaneously executed by the same effector(s) (e.g. a muscle or a joint). The process of movement execution involves a series of highly nonlinear elements; for instance, a motor unit of a muscle produces force only in the direction of muscle shortening, thus representing a threshold operator that transforms the bipolar (i.e. excitatory or inhibitory) information at its spinal input into a purely unipolar signal (i.e. muscle force). This tripartite research report addresses the contribution of the nonlinearity of neuromuscular elements to the coordination of different motor tasks simultaneously executed by the same limb. In this first part of the series, a new hypothesis for such a single-muscle multiple-task coordination is presented which suggests an essentially threshold-linear coordination mechanism. Control signals generated by the central nervous system for each individual movement independently and feedback information from peripheral receptors are linearly superimposed. This compound control/feedback signal is processed by a nonlinear limiter element reflecting the discontinuous properties of the muscle and its reflex circuitry. It is shown that threshold-linear interaction of descending commands and afferent feedback information can lead to complex interdependent patterns of compound motor action. This includes the possibility of gating (i.e. the ability of one movement pattern to constrain or even impede the execution of another pattern) and of delayed response initiation when simultaneously performing more than one voluntary motor task. A theoretical analysis of the threshold-linear coordination mechanism and an extensive experimental validation of the model is provided in part II and part III of the report.

Computer Simulation↗
PubMed2000

[Oculopharyngeal muscle dystrophy. Genetic diagnosis in a family in Germany].

Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant myopathy with almost benign course. Its clinical features include ptosis, dysphagia, and proximal limb muscle weakness. The OPMD gene has been localized to chromosome 14, causing expansions of GCG triplets. Scattered families with OPMD belonging to different ethnic groups have been described worldwide. We describe one from northern Germany. In genetic diagnosis, expansion of GCG triplets to 11 was observed, which proved that myopathy, which is very rare in Germany.

Blepharoptosis↗
PubMed2000

Response priming in the Simon paradigm. A transcranial magnetic stimulation study.

The Simon effect refers to the finding of faster responses when stimulus and response locations correspond than when they do not, although a nonspatial stimulus feature is task-relevant. These performance differences are usually accounted for by response priming processes directly induced by the task-irrelevant stimulus location. The present study investigated neural mechanisms of response priming in a Simon task at the level of the motor cortex with the help of transcranial magnetic stimulation (TMS) and motor evoked potentials (MEPs) in both arms. A single TMS was applied contralateral or ipsilateral to the requested response at the time point where response priming was at a maximum. The MEP effects depended on the stimulated hemisphere. Over the left hemisphere, MEP areas were larger when TMS was applied over the primed motor cortex. However, reduced MEPs for the nonprimed hemisphere fell short of significance. Over the right hemisphere, only a MEP reduction for nonprimed left-hand responses was present. Therefore, we conclude that mainly excitatory activation underlies response priming in a Simon task, whereas the role of inhibitory processes is tentative.

Adult↗