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Biomedical subjects

Christian Hofer

Publications and source records attributed to Christian Hofer.

12 recordsLinked to original sources

Posterior root-muscle reflexes elicited by transcutaneous stimulation of the human lumbosacral cord.

Continuous epidural stimulation of lumbar posterior root afferents can modify the activity of lumbar cord networks and motoneurons, resulting in suppression of spasticity or elicitation of locomotor-like movements in spinal cord-injured people. The aim of the present study was to demonstrate that posterior root afferents can also be depolarized by transcutaneous stimulation with moderate stimulus intensities. In healthy subjects, single stimuli applied through surface electrodes placed over the T11-T12 vertebrae with a mean intensity of 28.6 V elicited simultaneous, bilateral monosynaptic reflexes in quadriceps, hamstrings, tibialis anterior, and triceps surae by depolarization of lumbosacral posterior root fibers. The nature of these posterior root-muscle reflexes was demonstrated by the duration of the refractory period, and by modifying the responses with vibration and active and passive movements. Stimulation over the L4-L5 vertebrae selectively depolarized posterior root fibers or additionally activated anterior root fibers within the cauda equina depending on stimulus intensity. Transcutaneous posterior root stimulation with single pulses allows neurophysiological studies of state- and task-dependent modulations of monosynaptic reflexes at multiple segmental levels. Continuous transcutaneous posterior root stimulation represents a novel, non-invasive, neuromodulative approach for individuals with different neurological disorders.

Adult↗

Thermoacoustic tomography with integrating area and line detectors.

Thermoacoustic (optoacoustic, photoacoustic) tomography is based on the generation of acoustic waves by illumination of a sample with a short electromagnetic pulse. The absorption density inside the sample is reconstructed from the acoustic pressure measured outside the illuminated sample. So far measurement data have been collected with small detectors as approximations of point detectors. Here, a novel measurement setup applying integrating detectors (e.g., lines or planes made of piezoelectric films) is presented. That way, the pressure is integrated along one or two dimensions, enabling the use of numerically efficient algorithms, such as algorithms for the inverse radon transformation, for thermoacoustic tomography. To reconstruct a three-dimensional sample, either an area detector has to be moved tangential around a sphere that encloses the sample or an array of line detectors is rotated around a single axis. The line detectors can be focused on cross sections perpendicular to the rotation axis using a synthetic aperture (SAFT) or by scanning with a cylindrical lens detector. Measurements were made with piezoelectric polyvinylidene fluoride film detectors and evaluated by comparison with numerical simulations. The resolution achieved in the resulting tomography images is demonstrated on the example of the reconstructed cross section of a grape.

Acoustics↗

Electrical stimulation of denervated muscles: first results of a clinical study.

To evaluate the effects of electrical stimulation on denervated muscles in spinal cord injured humans, the EU Project RISE was started in 2001. The aims of this project are: to design and build sufficient stimulators; to develop stimulation protocols by means of mathematical models, animal experiments, and practice in humans with denervated lower limbs; to develop examination methods and devices for evaluation of electrical stimulation training effects; and to acquire basic scientific knowledge on denervated and stimulated denervated muscle. In the clinical study 27 spinal cord injured individuals were included, furthermore 13 pilot patients participated. After a series of initial examinations they underwent an electrical stimulation program for their denervated lower limb muscles. Some of the patients have already follow up examinations. A marked increase of muscle mass and quality was observed, the trophic situation of the denervated lower limbs had improved obviously.

Adult↗

Stimulation parameter optimization for FES supported standing up and walking in SCI patients.

Functional Electrical Stimulation (FES) to restore leg movement for standing up and walking (stepping) in SCI patients with intact lower motor neuron is used by several groups. Usually quadriceps muscles are stimulated for hip and knee extension, gluteus muscles for hip stabilization, and the common peroneal nerve to elicit the flexion reflex. The requirement to get a natural movement would need a huge number of stimulation channels--a request that could be easily fulfillled from the engineer's point of view but not from the point of practicability since each stimulated muscle requires two skin-attached electrodes resulting in a prolonged time for donning and doffing. In the described project a newly developed eight channel stimulator that can vary the stimulation parameters in many ways and over a wide range is used. The goal is to achieve a natural movement with a minimum of surface electrodes by optimizing the stimulation parameters. Seven experienced FES users and five unexperienced persons (all between Th4-Th11) participate in this study. Standing up can be significantly improved by optimizing the time delay between the onset of quadriceps and gluteus muscles (0.2-0.4 s) and the duration of the ramp. A 0.2 s delay gives good results in heavy patients while slower ramps (0.4 s) are required in slim patients. During stepping, gluteus muscle timing is not very crucial. Gluteus stimulation is turned off 0.1-0.2 s before quadriceps muscle and with the same delay turned on again. Of major influence on the gait quality is the timing during heel strike when peroneal stimulation is switched off and quadriceps stimulation is turned on. Six patients require 0.0-0.1 s where neither peroneal nor quadriceps stimulation is applied, the others require an overlap of 0.1-0.2 s. Activation of adductor muscles during standing up and during the swing phase helps to avoid hip abduction and improves knee trajectories.

Electric Stimulation Therapy↗

In vivo assessment of conduction velocity and refractory period of denervated muscle fibers.

Stimulation needle electromyography was used to study the muscle fiber conduction velocity and refractory period in 4 patients with long-term denervation of the lower limb muscles due to lesion of the conus cauda or cauda equina (2 untrained and 2 trained by functional electrical stimulation). In untrained patients, the results demonstrated that propagation velocity is reduced and refractory period of the muscle fiber is increased with time of denervation. The patients performing electrical stimulation training showed higher conduction velocities and reduced refractory period despite longer lasting denervation. This suggests that electrical stimulation training is effective to improve the electrical properties of the muscle fiber. Since the obtained data show a good correlation to other clinical tests and biopsy investigations, this method could serve as an additional measurement technique to specify the status of the denervated muscle. Further animal experiments and clinical studies are necessary to proof the results in comparison to more invasive established techniques.

Electric Stimulation↗

Use of real-time reverse transcriptase polymerase chain reaction assay and cell culture methods for detection of swine influenza A viruses.

OBJECTIVE: To evaluate sensitivity and specificity of a real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay performed on pooled nasal swab specimens, compared with virus isolation performed on individual nasal swab specimens by use of 2 cell culture lines for detection of swine influenza A viruses. SAMPLE POPULATION: 900 nasal swab specimens obtained from pigs at an abattoir and 62 nasal swab specimens submitted for diagnostic testing. PROCEDURES: Primers were chosen to amplify a conserved portion of the influenza virus matrix gene. Assay sensitivity was initially determined by testing serial dilutions of various subtypes of swine influenza viruses. Sensitivity and specificity were confirmed by use of nasal swab specimens with or without addition of known concentrations of influenza virus and further validated by testing nasal swab specimens obtained through an abattoir surveillance program or submitted for diagnostic testing. Aliquots of specimens were pooled in sets of 10, and results of real-time RT-PCR assays were compared with results of virus isolation of individual specimens in Madin Darby canine kidney (MDCK) and mink lung (Mv1Lu) cells. RESULTS: Real-time RT-PCR assay was highly specific (100%) and sensitive (88% to 100%). Among the 16 viruses isolated, 3 grew only in Mv1Lu cells and 3 grew only in MDCK cells. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate that real-time RT-PCR assay is a fast and accurate test for screening numerous nasal swab specimens for swine influenza virus. Some viruses were isolated in only MDCK or Mv1Lu cells, indicating that use of >1 cell line may be required to isolate a broad range of influenza A viruses.

Animals↗

Transcutaneous IL-2 uptake mediated by Transfersomes depends on concentration and fractionated application.

INTRODUCTION: Transfersomes (TF) are new, ultradeformable carriers with characteristics that enable them to penetrate the skin spontaneously. TFs are able to transport noninvasively both low- and high-molecular-weight molecules into the body. MATERIALS AND METHODS: TFs contain phosphatidylcholine and sodium cholate. Recombinant human interleukin-2 (Proleukin, Chiron) was added to the TFs and incubated for 24 h at 4 degrees C. The immunotransfersomes (ITF) were isolated from free interleukin-2 (IL-2) by filtration (Centrisart, Sartorius). Twenty-five thousand, 50,000 and 150,000 IU pure IL-2 and ITFs, which had been incubated with the same concentrations of IL-2, were applied subcutaneously (s.c.) (n = 8) and epicutaneously (e.c.) (n = 8) to mice. The IL-2 serum concentrations in the mice were then measured by ELISA after 2, 4, 6, 8, 10 and 24 h. Fractionation of the transdermal IL-2 application was also examined as a means of improving uptake. RESULTS: In concentrations of 25,000 and 50,000 IU IL-2, the subcutaneous application of ITFs resulted in a longer lasting IL-2 serum concentration than did the subcutaneous application of pure IL-2. While at 25,000 IU, the epicutaneous application of ITFs resulted in serum concentrations comparable to those resulting from s.c. application, at 50,000 and 150,000 IU, only 50% and 22.6% of the maximum serum concentration resulting from the s.c. application of pure IL-2 was obtained. Fractionating the transdermal IL-2 application improved uptake. CONCLUSION: We were able to show that biologically active IL-2 can be bonded to TFs up to 75%. It is possible to transport IL-2 through the skin using TFs. Both the concentration-dependent saturation of the TFs with IL-2 and fractionation of the application resulted in differing degrees of transcutaneous IL-2 uptake.

Administration, Cutaneous↗

Beneficial effects of immediate stenting after thrombolysis in acute myocardial infarction.

OBJECTIVES: The Southwest German Interventional Study in Acute Myocardial Infarction (SIAM III) investigated potentially beneficial effects of immediate stenting after thrombolysis as opposed to a more conservative treatment regimen. BACKGROUND: Treatment of acute myocardial infarction (AMI) by thrombolysis is compromised by Thrombolysis In Myocardial Infarction (TIMI) 3 flow rates of only 60% and high re-occlusion rates of the infarct-related artery (IRA). Older studies showed no benefit of coronary angioplasty after thrombolysis compared with thrombolytic therapy alone. This observation has been challenged by the superiority of primary stenting over balloon angioplasty in AMI. METHODS: The SIAM III study was a multicenter, randomized, prospective, controlled trial in patients receiving thrombolysis in AMI (<12 h). Patients of group I were transferred within 6 h after thrombolysis for coronary angiography, including stenting of the IRA. Group II received elective coronary angiography two weeks after thrombolysis with stenting of the IRA. RESULTS: A total of 197 patients were randomized, 163 patients fulfilled the secondary (angiographic) inclusion criteria (82 in group I, 81 in group II). Immediate stenting was associated with a significant reduction of the combined end point after six months (ischemic events, death, reinfarction, target lesion revascularization 25.6% vs. 50.6%, p = 0.001). CONCLUSIONS: Immediate stenting after thrombolysis leads to a significant reduction of cardiac events compared with a more conservative approach including delayed stenting after two weeks.

Aged↗

Denervated muscles in humans: limitations and problems of currently used functional electrical stimulation training protocols.

Prior clinical work showed that electrical stimulation therapy with exponential current is able to slow down atrophy and maintain the muscle during nonpermanent flaccid paralysis. However, exponential currents are not sufficient for long-term therapy of denervated degenerated muscles (DDMs). We initiated a European research project investigating the rehabilitation strategies in humans, but also studying the underlying basic scientific knowledge of muscle regeneration from satellite cells or myoblast activity in animal experiments. In our prior study, we were able to show that high-intensity stimulation of DDMs is possible. At the beginning of training, only single muscle twitches can be elicited by biphasic pulses with durations of 120-150 ms. Later, tetanic contraction of the muscle with special stimulation parameters (pulse duration of 30-50 ms, stimulation frequency of 16-25 Hz, pulse amplitudes of up to 250 mA) can improve the structural and metabolic state of the DDMs. Because there are no nerve endings for conduction of stimuli, large-size, anatomically shaped electrodes are used. This ensures an even contraction of the whole muscle. Contrary to the current clinical knowledge, we were able to stimulate and train denervated muscle 15-20 years after denervation. The estimated amount of muscle fibers that have to be restored is about 2-4 million fibers in each m. quadriceps. To rebuild such a large number of muscle fibers takes up to 3-4 years. Despite constant stimulation parameters and training protocols, there is a high variation in the developed contraction force and fatigue resistance of the muscle during the first years of functional electrical stimulation.

Electric Stimulation Therapy↗

The Vienna functional electrical stimulation system for restoration of walking functions in spastic paraplegia.

An eight-channel stimulation system, currently intended for stimulation of lower extremities, was developed and is introduced. The major development goals were easy handling, modularity to make the system easily adaptable for other functional electrical stimulation (FES) applications, and a wide stimulation parameter range for application-specific parameter optimization. For paraplegic stepping, the system worn by the patient consists of 2 four-channel stimulation modules, a central unit holding the battery and circuitry for power management and communication control, a wireless remote control unit, and a palmtop computer as the main control and input device. A software package for Microsoft Windows supports the design and optimization of stimulation sequences in the rehabilitation center. First tests with patients familiar with FES showed smoother movements during stepping and acceptable good handling. In combination with the PC software, the required stimulation sequences could be created in a very short time.

Computer Systems↗

A stimulator for functional activation of denervated muscles.

In recent years various studies proved that electrical stimulation can improve contractile capability and restore muscle function in long-term denervated degenerated muscles. The low excitability of the muscle cells at the initial stage of training and surrounding connective tissue, acting as an electrical shunt, require special stimulation parameters. Until now, no appropriate devices (stimulators) are commercially available. Therefore, we were forced to design our own stimulators. The control unit of the stimulators is based on a microprocessor for maximum flexibility regarding the generation of the parameters such as pulse amplitudes, pulse width, frequency, stimulation times, ramps, and so on. In addition, the microprocessor design allows recording of compliance data such as stimulation date, time, duration, and used programs. The constant voltage output stage of the stimulator is able to generate biphasic charge balanced stimulation impulses with a pulse width of 1 to 300 ms, voltage amplitudes up to +/-80 V (160 VPP), and stimulation currents up to 250 mA. To prevent direct current due to inexact charge compensation, the electrode outputs are decoupled capacitively. Simultaneous 2 channel stimulation with independent intensity levels is possible. The stimulators are programmed using a notebook or a personal digital assistant via infrared serial interface. This concept guarantees the application of correct stimulation parameters because the patient has only access to parameters that are preprogrammed for him in the outpatient clinic. For the home based training, access is limited to variation of intensity within preprogrammed limits. For safety reasons, the portable unit is powered by an internal rechargeable battery. High efficiency switched voltage regulators are used to provide the different required voltage levels while ensuring an acceptable operating time of the stimulator.

Electric Power Supplies↗

Muscle biopsies show that FES of denervated muscles reverses human muscle degeneration from permanent spinal motoneuron lesion.

This paper presents biopsy analyses in support of the clinical evidence of muscle recovery induced by a new system of life-long functional-electrical-stimulation (FES) training in permanent spinal-motoneuron-denervated human muscle. Not earlier than 1 year after subjects experienced complete conus cauda lesion, their thigh muscles were electrically stimulated at home for several years with large skin surface electrodes and an expressly designed stimulator that delivered much longer impulses than those presently available for clinical use. The poor excitability of long-term denervated muscles was first improved by several months of twitch-contraction training. Then, the muscles were tetanically stimulated against progressively increased loads. Needle biopsies of vastus lateralis from long-term denervated subjects showed severe myofiber atrophy or lipodystrophy beginning 2 years after spinal cord injury (SCI). Muscle biopsies from a group of 3.6- to 13.5-year denervated subjects, who underwent 2.4 to 9.3 years of FES, show that this progressive training almost reverted long-term muscle atrophy/degeneration.

Adult↗