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Biomedical subjects

J Elek

Publications and source records attributed to J Elek.

16 recordsLinked to original sources

Remote F-wave changes after local botulinum toxin application.

OBJECTIVE: Although the therapeutic effects of botulinum toxin A can be explained by its action at the neuromuscular junction, central or more proximal effects have also been discussed. METHODS: Eleven patients with torticollis spasmodicus and 3 patients with writer's cramp were studied before and 1 and 5 weeks after the first treatment with botulinum toxin. We measured compound muscle action potentials (CMAPs), motor conduction velocities (MCVs), the shortest (SFL) and the mean F-wave latencies (MFL) and F-wave persistence (30 trials) of untreated muscles for each side (ulnar nerve-abductor digiti minimi muscle, peroneal nerve-tibialis anterior muscle). RESULTS: CMAPs and MCVs showed no significant changes. For both nerves, however, SFL and MFL were prolonged slightly 1 week after treatment and returned to about baseline after 5 weeks (t test). The F-wave persistence was reduced 1 week after treatment for the right ulnar and both peroneal nerves (t test). CONCLUSIONS: These results are not likely due to an impairment of neuromuscular transmission. Instead, we propose a decreased excitability of alpha-motoneurons supplying non-treated muscles. A reduction of muscle spindle activity or changes of the recurrent inhibition are discussed as possible causes.

Action Potentials↗

Activation of high-threshold motor units in man by transcranial magnetic stimulation.

Motor units (MUs) with low voluntary recruitment thresholds are the first to be activated by transcranial magnetic stimulation. It is not clear, however, if high-threshold MUs can also be activated and if they contribute to motor evoked potentials (MEPs). We therefore studied 11 high-threshold motor units in the first dorsal interosseous muscle of 11 healthy subjects. Voluntary recruitment thresholds ranged from 22 to 41% (29.5 +/- 5.6%; mean +/- S.D.) of maximal muscle force. When MUs were driven at their recruitment thresholds, transcranial magnetic stimuli were applied to the vertex. Peri-stimulus time histograms of MU discharges were constructed. All MUs studied revealed a period of increased firing probability at 19-27 ms after the stimulus (primary peak). Stimulus intensities were lower by 10-57% of the maximal stimulator output than required to produce near maximal MEPs in conventional surface EMG recordings in the same subjects. We conclude that high-threshold MUs can be activated by transcranial magnetic stimulation and that they contribute to conventionally recorded MEPs.

Adult↗

[The use of endoprostheses (stents) in airway stenosis].

Six patients with obstruction of the trachea were treated with silicone rubber endothracheal stents implanted with flexible bronchoscope. In every case the stent caused significant clinical improvement of the ventilation. At the postintubation stenosis the stent can result a final recovery, at the malignant processes the implantation seems to be a new palliative method.

Accidents↗

F waves and motor unit size.

M responses and twitch contractions were evoked in single motor units (MUs) of the first dorsal interosseus muscle by intramuscular microstimulation of motor axons. Two-hundred nine MUs were studied in 21 subjects. Thirty-five MUs (17%) showed F waves in addition to M responses. Twitch force was used to provide an indirect measure of MU size; additionally, twitch contraction time was measured. There was no select group of MUs generating F waves with regard to the above contraction parameters. However, four of five MUs with very high twitch forces, above 70 mN, generated F waves. We conclude that MUs of all sizes produce F waves with similar probability. Only few MUs with very strong twitch forces, i.e., very large MUs, may be more subject to F-wave production and may be involved in the generation of the so-called repeater F waves.

Action Potentials↗

Attenuation of pathological tremors by functional electrical stimulation. I: Method.

In this study we explored the possibility of suppressing pathological tremors using closed-loop functional electrical stimulation (FES) to activate the tremorogenic muscles out-of-phase. A displacement signal monitored with a transducer was filtered so as to be "tuned" to the tremor frequency at the wrist or elbow. The filtered signal was used to amplitude-modulate the electrical stimulation. The design process was based on measurements of the open-loop frequency response characteristics of the forearm and hand to stimulation of the elbow and wrist flexors and extensors in a number of subjects. These data allowed us to identify closed-loop configurations, which attenuated 2-5 Hz tremors substantially, while only minimally attenuating functional movements in the 0-1 Hz range. There was a fairly delicate balance between efficacy and the risk of instability. However, designs were identified that offered enough tremor suppression and adequate immunity to muscle/load variations for the technique to be considered seriously for clinical application.

Electric Stimulation↗

Attenuation of pathological tremors by functional electrical stimulation. II: Clinical evaluation.

In this study we evaluated a technique for tremor suppression with functional electrical stimulation (FES), the technical details of which were described in the previous paper. Three groups of patients were investigated: those with essential tremor, parkinsonian tremor, and cerebellar tremor associated with multiple sclerosis. In each group, tremor was attenuated by significant amounts (essential tremor: 73%; parkinsonian tremor: 62%; cerebellar tremor: 38%). These attenuations were in good accord with predictions based on the dynamic analyses and filter designs derived in the previous paper. With filters "tuned" to the lower mean tremor frequency encountered in the cerebellar patients, more attenuation was possible in this group as well. We identified some practical limitations in the clinical application of the technique in its present form. The most important was that in daily use, only one antagonist pair of muscles can realistically be controlled. At first sight, this restricts the usefulness of the system to patients with single-joint tremors. However, the concomitant use of mechanical orthoses may broaden the scope of application.

Adult↗

[Is the origin of the F-wave dependent on the magnitude of the motor unit?].

It is still unknown why only few motor units (MUs) generate F-waves in response to supramaximal stimulation of a motor nerve. Therefore we investigated whether the F wave production might depend on MU-size. According to the size principle of Henneman we used the twitch force as indirect measure of MU-size. MU twitch force was determined applying the technique of intramuscular microstimulation of single motor axons. 127 MUs were analysed in 16 normal subjects. F-waves were observed in 35 MUs (27%). It was found that MUs of different sizes produced F-waves with approximately the same probability. Obviously size is not a relevant factor for the capability of a MU to produce F-waves. Only the few very large MUs of a pool may have an increased tendency to produce F-waves because four of five MUs with extremely large twitch forces (> 70 mN) generated F-waves.

Adult↗

In-series compliance of gastrocnemius muscle in cat step cycle: do spindles signal origin-to-insertion length?

1. It has been claimed that stretch in the non-contractile (extramysial) portion of muscles is substantial, and may produce large discrepancies between the origin-to-insertion muscle length and the internal length variations 'seen' by muscle spindle endings. 2. In eight pentobarbitone-anaesthetized cats, we estimated stretch in the extramysial portion of medial gastrocnemius (MG) muscle with a method similar to the spindle null technique. 3. Length variations of MG previously monitored in a normal step cycle were reproduced with a computer-controlled length servo. The responses of test MG spindle endings were monitored in dorsal root filaments. Distributed stimulation of ventral root filaments, rate-modulated by the step-cycle EMG envelope, served to reproduce step-cycle forces. The filaments were selected so as to have no fusimotor action on the test spindle. 4. Spindle responses in active cycles were compared with those in passive cycles (stretch, but no distributed stimulation). In some cases concomitant tonic fusimotor stimulation was used to maintain spindle responsiveness throughout the cycle, both in active and passive trials. Generally, small discrepancies in spindle firing were seen. The passive trials were now repeated, with iterative adjustments of the length function, until the response matched the spindle firing profile in the active trial. The spindle 'saw' the same internal length change in the final passive trial as in the active trial. Any difference between the corresponding length profiles was attributed to extramysial displacement. 5. Extramysial displacement estimated in this was was maximal at short mean muscle lengths, reaching about 0.5 mm in a typical step cycle (force rising from 0 to 10 N). At longer mean muscle lengths where muscle force rose from say 2 to 12 N in the cycle, extramysial displacement was in the range 0.2-0.4 mm. 6. Except at very short lengths, the displacement was probably mainly tendinous. On this assumption, our results suggested that the stiffness of the MG tendinous compartment was force related, and about double that of cat soleus muscle at any given force. Calculations indicated that though the stretch was small, the MG tendon would store and release enough strain energy per cycle to contribute significantly to the E3 phase of the step cycle. The discrepancies in spindle firing were generally quite subtle, so we reject the claim that extramysial stretch poses a serious difficulty for inferences about fusimotion from chronic spindle afferent recordings.

Action Potentials↗

The impact of paired motor unit discharges on tremor.

We studied paired discharges (PDs) of single motor units (MUs) of the first dorsal interosseus muscle in parkinsonian and essential tremor. The number of PDs increased with increasing tremor strength and the duration of their intervals shortened. The amplitudes of the single tremor beats showed a significant negative correlation to the duration of the intervals of the preceding PDs. It is concluded that PDs play an important role as tremor amplifiers. The basic mechanism is probably the more than linear summation of two twitch contractions with short interval which is known from animal experiments.

Adult↗

[Double discharges of motor units and tremor strength].

The relationship between the double-discharges (DDs) of single motor units (MUs) and the tremor strength was studied in 7 patients with parkinsonism and 3 with essential tremor. The potentials of single MUs and the force of the first dorsal interosseus muscle were recorded during slight isometric contractions. The rate of DDs and their interval duration were correlated with the global tremor strength and the amplitudes of the single tremor beats. With increasing tremor strength, the rate of DDs increased and the duration of their intervals decreased. It is concluded that DDs act as tremor amplifiers. This effect is probably accounted for by a more than linear summation of two consecutive MU contractions with short interval which is known from animal experiments.

Adult↗

Fatty degeneration in cultured hepatocytes. A new experimental model.

In co-cultures of adult rat hepatocytes and a neonatal rat liver cell line, severe fatty degeneration was induced by the addition of 50% rat serum. The light and electron microscopic patterns did not differ significantly from those of in vivo fatty degeneration and the changes were reversible on removal of the serum. The in vitro system is considered to simulate some forms of fatty degeneration of the liver and to be suitable for testing the effects of liver-protecting agents.

Animals↗

Morphological investigations on co-cultures of rat hepatocytes and the neonatal liver cell line RL 19.

Hepatocytes isolated from mature rats were cultivated together with proliferating liver cells derived from newborn rats (RL 19 line). The hepatocytes of the co-cultures were viable for long period and preserved their glucose-6-phosphatase activity and glycogen content longer than the mature rat hepatocytes cultured alone. Electron microscopy revealed that the RL 19 cells were covering the hepatocytes and growing beneath them. Both the RL 19 cells and the adult hepatocytes established tight contact with each other, but between the two cell types there was always a gap bridged by microvilli and resembling Disse's space. It is assumed that the envelope formed by the RL 19 cells may have a role in the maintenance of the differentiated hepatocyte structure.

Age Factors↗

Microarray-based expression profiling in prostate tumors.

High throughput gene expression profiling is increasingly becoming a desirable method for identifying genes differentially expressed in disease versus normal tissues. Microarrays and gene chips containing hundreds to thousands of genes of interest, both known and novel, can be used to establish the expression profile of numerous genes in a single experiment. In order to validate the hits emerging out of such an experiment it is necessary to use an appropriate panel of the cDNA repository. We investigated the usefulness of such a method to identify prostate cancer-specific genes. A microarray containing 588 known genes was analyzed using cDNA probes derived from normal and three independent prostate tumors. At least 19/588 genes were found to be differentially expressed in the tumors in comparison to the normal tissue. Among the nine test genes chosen, one gene, Glutathione-S-transferase theta 1 (GSTT1), showed a correlation with the microarray results when analyzed by RT-PCR. Using a comprehensive panel of normal and tumor tissues and cancer-derived cell lines, we have rapidly validated the expression relevance of GSTT1 in solid tumors. The microarray was also useful in the preliminary identification of androgen-regulated genes in the prostate tumor models. These results indicate that microarray in combination with a relevant cDNA repository can facilitate rapid identification of potential targets for therapy and diagnosis of prostate and other cancers.

Female↗

Relevant genomics of neurotensin receptor in cancer.

The expressed sequence tag (EST) databases are an attractive starting point for gene discovery for diseases like cancer. Validation of gene targets from these sequences (both known and novel) in cancers requires a comprehensive expression profiling. We identified from the Cancer Gene Anatomy Project database (CGAP), a hit called neurotensin receptor (NT-r) that was expressed in the pancreatic cancer cDNA libraries. Neurotensin (NT), a neuroendocrine peptide, exerts trophic effects in vivo and stimulates the growth of cancer-derived cell lines in vitro. High affinity neurotensin receptors (NT-r) are expressed in cancer-derived cell lines and in some primary tumors. To date, a comprehensive expression profile of the NT-r in diverse cancers and normal tissues has not been reported. A cancer-selective expression of NT-r, if demonstrable, may provide a basis for a diagnostic and potential therapeutic utility. We demonstrate that the NT-r is expressed in a variety of cancer-derived cell lines as well as primary tumors, but only in a select few normal tissues. The expression of NT, on the other hand, was detected in many normal tissues, but not in the cancer-derived cell lines. The NT expression however, was detected in the primary tumors. We further demonstrate that NT expression is stimulated by androgen deprivation in the prostate cancer models. These results demonstrate the usefulness of a panel of cDNA repository for rapid validation of potential cancer targets.

Breast Neoplasms↗