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Biomedical subjects

W Mayr

Publications and source records attributed to W Mayr.

At least 19 recordsLinked to original sources

Atrophy, but not necrosis, in rabbit skeletal muscle denervated for periods up to one year.

Our understanding of the effects of long-term denervation on skeletal muscle is heavily influenced by an extensive literature based on the rat. We have studied physiological and morphological changes in an alternative model, the rabbit. In adult rabbits, tibialis anterior muscles were denervated unilaterally by selective section of motor branches of the common peroneal nerve and examined after 10, 36, or 51 wk. Denervation reduced muscle mass and cross-sectional area by 50-60% and tetanic force by 75%, with no apparent reduction in specific force (force per cross-sectional area of muscle fibers). The loss of mass was associated with atrophy of fast fibers and an increase in fibrous and adipose connective tissue; the diameter of slow fibers was preserved. Within fibers, electron microscopy revealed signs of ultrastructural disorganization of sarcomeres and tubular systems. This, rather than the observed transformation of fiber type from IIx to IIa, was probably responsible for the slow contractile speed of the muscles. The muscle groups denervated for 10, 36, or 51 wk showed no significant differences. At no stage was there any evidence of necrosis or regeneration, and the total number of fibers remained constant. These changes are in marked contrast to the necrotic degeneration and progressive decline in mass and force that have previously been found in long-term denervated rat muscles. The rabbit may be a better choice for a model of the effects of denervation in humans, at least up to 1 yr after lesion.

Animals↗

Implantable device for long-term electrical stimulation of denervated muscles in rabbits.

Although denervating injuries produce severe atrophic changes in mammalian skeletal muscle, a degree of functional restoration can be achieved through an intensive regime of electrical stimulation. An implantable stimulator was developed so that the long-term effects of different stimulation protocols could be compared in rabbits. The device, which is powered by two lithium thionyl chloride batteries, is small enough to be implanted in the peritoneal cavity. All stimulation parameters can be specified over a wide range, with a high degree of resolution; in addition, up to 16 periods of training (10-180 min) and rest (1-42 h) can be set in advance. The microcontroller-based device is programmed through a bidirectional radiofrequency link. Settings are entered via a user-friendly computer interface and annotated to create an individual study protocol for each animal. The stimulator has been reliable and stable in use. Proven technology and rigorous quality control has enabled 55 units to be implanted to date, for periods of up to 36 weeks, with only two device failures (at 15 and 29 weeks). Changes in the excitability of denervated skeletal muscles could be followed within individual animals. Chronaxie increased from 3.24 +/- 0.54 ms to 15.57 +/- 0.85 ms (n = 55, p < 0.0001) per phase in the 2 weeks following denervation.

Animals↗

Autoimmune diseases in vitiligo: do anti-nuclear antibodies decrease thyroid volume?

An increased prevalence of autoimmune thyroiditis (AT) in vitiligo patients is well known. The aim of this study was firstly, to evaluate the clinical course of patients with both vitiligo and AT and secondly, to identify additional autoimmune disorders affecting the thyroid gland in a large cohort of vitiligo patients. We analysed a study group of 106 vitiligo patients and 38 controls. A detailed thyroid examination including sonography was performed in all study participants. In addition, the study participants were HLA typed and screened for various autoimmune disorders. AT was significantly more frequent in vitiligo patients than in controls (21%versus 3%; P < 0.01). In 12 of the 22 patients with AT, vitiligo was the initial disease preceding AT by 4-35 years. In the other 10 patients with AT, both vitiligo and AT were diagnosed within one year. There were two individuals with diabetes mellitus type 1 and a single patient with Addison's disease. Anti-nuclear antibody (ANA), anti-smooth muscle cell antibody, and parietal cell antibody levels occurred with a similar frequency in patients and controls. In all vitiligo patients with both elevated ANA levels and AT (n = 6), the atrophic but not the goitrous variant was diagnosed. These vitiligo patients with both AT and elevated ANA levels had a significantly smaller thyroid volume compared to the vitiligo patients with AT whose ANA levels were normal (6.7 +/- 4.5 ml versus 13.4 +/- 9.1 ml, respectively; P < 0.05). The same was found in the entire study group: Thyroid volume of all vitiligo patients (with or without concomitant AT) was significantly smaller in the presence of ANA (6.9 +/- 5.3 versus 10.5 +/- 5.9 ml, respectively; P < 0.05). However, this phenomenon was not observed in the control group. There was a trend for a decreased frequency of HLA-DR3 (6.7%versus 23%) in our study group, but after correction for the number of comparisons, no HLA-allele was statistically significant associated neither with vitiligo nor with multiple autoimmune diseases in our patient sample. Our findings suggest that AT is the most frequent autoimmune disease associated with vitiligo. In our patients, AT presented simultaneously or after the onset of vitiligo but not before. Elevated ANA levels were associated with the atrophic variant of AT and may affect the volume of the thyroid gland, and there was no statistically significant association with the HLA system.

Adolescent↗

Basic design and construction of the Vienna FES implants: existing solutions and prospects for new generations of implants.

We can distinguish 3 generations of FES implants for activation of neural structures: 1. RF-powered implants with antenna displacement dependent stimulation amplitude; 2. RF-powered implants with stabilised stimulation amplitude; and 3. battery powered implants. In Vienna an 8-channel version of the second generation type has been applied clinically to mobilisation of paraplegics and phrenic pacing. A 20-channel implant of the second generation type for mobilisation of paraplegics and an 8-channel implant of the third generation type for cardiac assist have been tested in animal studies. A device of completely new design for direct stimulation of denervated muscles is being tested in animal studies. There is a limited choice of technologically suitable biocompatible and bioresistant materials for implants. The physical design has to be anatomically shaped without corners or edges. Electrical conductors carrying direct current (D.C.) have to be placed inside a hermetic metal case. The established sealing materials, silicone rubber and epoxy resin, do not provide hermeticity and should only embed DC-free components. For electrical connections outside the hermetic metal case welding is preferable to soldering; conductive adhesives should be avoided. It is advisable to use a hydrophobic oxide ceramic core for telemetry antenna coils embedded in sealing polymer. Cleaning of all components before sealing in resin is of the utmost importance as well as avoidance of rapid temperature changes during the curing process.

Animals↗

Functional and biological test of a 20 channel implantable stimulator in sheep in view of functional electrical stimulation walking for spinal cord injured persons.

A newly developed implantable stimulator with 20 output channels, mainly intended for the stimulation of lower extremities in paraplegics, was implanted in 6 sheep over a time period of 26 weeks. Five epineural electrodes each were used to contact various nerves at different locations to elicit hip and knee extension and flexion and to make carrousel and selective stimulation possible. Different electrode application strategies in view of paraplegic standing and walking were investigated. Additional implanted electrodes allowed M-wave monitoring for selectivity investigations in 3 sheep. Stimulator, electrode leads, and electrodes proved to be reliable. Selective stimulation with electrodes placed on the trunk of the sciatic nerve could be demonstrated but with bad reproducibility. Histological investigation of the tissues surrounding electrodes and leads showed the expected stable foreign body response. Strong hip and knee extension could be gained in all cases while only weak flexion forces could be elicited in most cases. Muscle biopsies showed that daily stimulation for 8 h at threshold level caused an increase in muscle Type I fibers and a decrease in Type IIc fibers. Implants and electrodes fulfill the most important functional and biological criteria for their clinical application for paraplegic walking. The intention to provide selective flexion functions via epineural stimulation could not be demonstrated sufficiently in this animal model.

Animals↗

Improvement of thigh muscles by neuromuscular electrical stimulation in patients with refractory heart failure: a single-blind, randomized, controlled trial.

OBJECTIVE: To determine the impact of an 8-wk neuromuscular stimulation program of thigh muscles on strength and cross-sectional area in patients with refractory heart failure listed for transplantation. DESIGN: Forty-two patients with a stable disease course were assigned randomly to a stimulation group (SG) or a control group (CG). The stimulation protocol consisted of biphasic symmetric impulses with a frequency of 50 Hz and an on/off regime of 2/6 sec. RESULTS: Primary outcome measures were isometric and isokinetic thigh muscle strength and muscle cross-sectional area. Our results showed an increase of muscle strength by mean 22.7 for knee extensor and by 35.4 for knee flexor muscles. The CG remained unchanged or decreased by -8.4 in extensor strength. Cross-sectional area increased in the SG by 15.5 and in the CG by 1.7. CONCLUSIONS: Activities of daily living as well as quality of life increased in the SG but not in the CG. Subscales of the SF-36 increased significantly in the SG, especially concerning physical functioning by +7.5 (1.3-30.0), emotional role by +33.3 (0-66.6), and social functioning by +18.8 (0-46.9), all P < 0.05. Neither a change nor a decrease was observed in the CG. Neuromuscular electrical stimulation of thigh muscles in patients with refractory heart failure is effective in increasing muscle strength and bulk and positively affects the perception of quality of life and activities of daily living.

Activities of Daily Living↗

Test bed with force-measuring crank for static and dynamic investigations on cycling by means of functional electrical stimulation.

Cycling by means of functional electrical stimulation (FES) is an attractive training method for individuals with paraplegia. The physiological benefits of FES are combined with the psychological incentive of independent locomotion. In addition, cycling has the advantage in that the generated muscle forces are converted into drive power with relatively high efficiency compared to other means of locomotion, e.g., walking. For the design of an appropriate cycling device and the development of optimal stimulation patterns, it has to be investigated how the geometry for FES cycling, influenced by individual parameters of the FES-generated drive torques and the magnitude of variations among subjects with paraplegia, can be optimized. This study shows the design of a freely adjustable test bed with additional motor drive which allows static and dynamic measurements of force components and drive torque at the crank. Furthermore, the influence of geometry and various individual parameters on FES pedaling can be tested for each subject individually. A pedal path realized by a three-bar linkage that was optimized according to preliminary simulations further increases leg cycling efficiency. Safety precautions avoid injuries in case of excessive forces, e.g., spasms. Test results illustrate the application of the test bed and measurement routines. A test series with four paraplegic test persons showed that the presented static and dynamic measurement routines allow to provide optimal stimulation patterns for individual paraplegic subjects. While pedaling with these optimal stimulation patterns only negligible negative active drive torques, due to active muscle forces, were applied to the crank and sufficient drive power was generated to power a cycle independently.

Adult↗

Pruritometer 2: portable recording system for the quantification of scratching as objective criterion for the pruritus.

Studies to evaluate therapies for itching (pruritus) related diseases often require the quantification of the itch sensation. Like all subjective symptoms the evaluation of itching is difficult and can only be done indirectly. With the Pruritometer 2 a measuring system is introduced that evaluates itching by detecting scratching movements. Based on the Pruritometer 1, that processes the signals of a piezoelectric vibration sensor, fixed on the midfinger of the patients dominant hand, and triggers a simple counter, the Pruritometer 2 allows to store the scratch activity during a 24 hours period. For each adjustable time slice of this time period, the amount of scratches and the scratch intensity are recorded. All data can be transferred to a PC via infrared link for further processing with a standard software package. An additional PC-software allows to set various parameters for optimal scratch detection and to test the patient attached system, also via the infrared link. All electronic components are shockproof encapsulated in a milled housing and are attached to a textile watchstrap that is worn by the patient like a wristwatch.

Equipment Design↗

13-week drinking water toxicity study of hydrogen peroxide with 6-week recovery period in catalase-deficient mice.

A GLP OECD guideline study was conducted to evaluate the subchronic toxicity of hydrogen peroxide (HP) when administered continuously in the drinking water of catalase-deficient (C57BL/6N) mice and reversibility of toxic effects. Groups of mice (15/sex/group) received solutions of 0, 100, 300, 1000 or 3000 ppm HP in distilled water for 13 weeks; five/sex/group continued on untreated distilled water for an additional 6 weeks. Animals drinking 3000 ppm HP exhibited depressed water and food consumption and body weight. Females drinking 1000 ppm HP had reduced water consumption with intermittent effects on food consumption, but no body weight effects. HP administration did not produce any mortality, clinical signs, hematological effects or organ weight effects on brain, liver, kidneys, adrenals, testes, heart or spleen. Total protein and globulin were depressed among high dose males. Mild to minimal duodenal mucosal hyperplasia was noted in animals receiving 1000 and 3000 ppm HP and one male receiving 300 ppm for 13 weeks. There were no other histopathological findings. All effects noted during the treatment period, including the duodenal hyperplasia, were reversible during the 6-week recovery period. Females dosed with 300-3000 ppm HP during the treatment period showed increased water consumption during the recovery period. The no-observed-effect level (NOEL), based on duodenal mucosal hyperplasia, is 100 ppm in drinking water or 26 and 37 mg/kg/day HP, respectively, for males and females.

Acatalasia↗

[EMG monitoring in functional electrostimulation].

When using functional electrical stimulation (FES), correct adjustment of stimulation parameters, and monitoring of the stimulated muscle is mandatory if tissue damage is to be avoided. Although several FES systems are already in regular use, a method for direct muscle monitoring is still lacking. This paper investigates the suitability of the electromyogram (EMG) for such a purpose. In six sheep, the right latissimus dorsi muscle (LDM) and the associated thoracodorsal nerve were exposed. Stimulation was effected via electrodes placed on the nerve. Three electrodes were placed in the LDM for EMG recording, and the tendon was connected to a force transducer for isometric force measurement. Stimulation was applied for one second (burst), followed by a three-second pause. The stimulation current was increased in 0.2 mA steps, starting at 0 mA and ending at 4 mA. Throughout the investigation, the EMG signal was monitored with an oscilloscope. In addition, the EMG signal and the force transducer signal were recorded for subsequent analysis. An analysis of the data of all six sheep revealed an almost linear relationship between muscle force and m-wave amplitude (magnitude of r = 0.95, p < 0.001). M-wave monitoring during EMG recording with three intramuscular electrodes is a reliable method of monitoring FES-induced muscle activity, but the absolute force cannot be measured.

Animals↗

[Distraction osteogenesis with a fully implantable system. Experimental study].

Distraction osteogenesis using external or intraoral devices is an established method for lengthening the human mandible. In this preliminary study on sheep, a completely implanted device for mandibular lengthening is presented. After osteotomy of the mandible, the electromechanical device was fixed to the mandible and the power and control unit were inserted subcutaneously in the neck region. After a healing period of 5 days, the device was activated magnetically and allowed calibrated distraction steps of 0.04 mm/h, achieving a total of 1.0 mm per day. With this method, it was possible to lengthen the mandible automatically over a period of 14 days without transmucosal activation. In our study, this newly designed internal device was successfully used for distraction osteogenesis, and a maximum mandibular lengthening of 13.6 mm was achieved. Further research is necessary to achieve progression to human clinical application in the near future.

Animals↗

Multifunctional implantable nerve stimulator for cardiac assistance by skeletal muscle.

Different methods are used, clinically and experimentally, to assist severely impaired heart function by means of skeletal muscle. The efficiency of these methods is restricted by skeletal muscle losing strength after transpositioning and during conditioning and not being sufficiently resistant to fatigue. This is mainly due to the nonphysiological activation of the nerves by electrical stimulation. We have developed a battery operated, ECG triggered multichannel implant that is capable of implementing various advanced stimulation techniques. The stimulator can activate 2 skeletal muscles via the motor nerves. It allows for application of multichannel stimulation methods, i.e., carousel stimulation and sequential stimulation, as well as the programming of optimized pulse trains. Synchronization delay and burst duration can be automatically and dynamically adapted to the heart rate. The multichannel stimulator is hermetically sealed in a titanium case. Its calculated life span on the basis of the integrated battery is 3-5 years, depending on the programmed stimulation parameters. The implant dimensions are 65 x 17 mm (diameter x height), and it weighs 93 g. The implant has been tested in vitro as well as in vivo.

Animals↗

Long-term electromyogram recording from the posterior cricoarytenoid muscle as a potential biological trigger for phrenic pacing: results of an animal study.

Diaphragm pacing has been used to restore respiration in approximately 1,000 patients worldwide suffering from high quadriplegia or from central alveolar hypoventilation syndrome. Compared with conventional mechanical ventilation, electrophrenic respiration (EPR) reduces the risk of pulmonary infections and increases the mobility of patients. Voluntary activation of the pacemaker during speech would improve patients' quality of life and allow application of EPR in a more physiological way. An animal study was performed to investigate the electromyogram (EMG) of the posterior cricoarytenoid (PCA) muscle and the movement of the glottis via impedance measurement (electroglottography) with the aim to examine reproducibility and stability of the recordings from the PCA muscle as a potential biological trigger for a phrenic pacemaker. The EMG of the PCA muscle was recorded via implanted electrodes for a 200 day period. The EMG signal proved stable for that period, artifacts caused by movements can be suppressed, and swallowing can be detected. In contrast, impedance measurement to detect movement of the glottis proved not useful. Based on the results of this study, the use of the PCA EMG as a biological trigger for a phrenic pacemaker has to be considered a realistic option.

Animals↗