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Estimating paternity and genetic relatedness is central to many empirical and theoretical studies of social insects. The two important measures of a queen's mating number are her actual number of mates and her effective number of mates. Estimating the effective number of mates is mathematically identical to the problem of estimating the effective number of alleles in population genetics, a common measure of genetic variability introduced by ). We derive a new bias-corrected estimator of effective number of types (mates or alleles) and compare this new method to previous methods for estimating true and effective numbers of types using Monte Carlo simulations. Our simulation results suggest that the examined estimators of the true number of types have very similar statistical properties, whereas the estimators of effective number of types have quite different statistical properties. Moreover, our new proposed estimator of effective number of types is approximately unbiased, and has considerably lower variance than the original estimator. Our new method will help researchers more accurately estimate intracolony genetic relatedness of social insects, which is an important measure in understanding their ecology and social behaviour. It should also be of use in population genetic studies in which the effective number of alleles is of interest. [ABSTRACT FROM AUTHOR]

Background: The purpose of the study was to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of piperacillin and tazobactam during high-volume haemodiafiltration (HVHDF)., Methods: A single dose of piperacillin/tazobactam (4/0.5 g) was administered as 30 minute infusion during HVHDF to 10 patients with acute kidney injury due to septic shock. Arterial blood samples were collected before and at 30 or 60 min intervals over 8 h (12 samples) after study drug administration. Concentrations of piperacillin and tazobactam were determined by HPLC-MS/MS. R software was used for population PK analysis and Monte Carlo Simulation of probability of PK/PD target attainment (PTA) in 1000 subjects., Results: A total of 101 samples were collected during HVHDF. The median (IQR) estimated glomerular filtration rate of the patients was 16 (11.25-27.5) ml/min/1.73 m(2) and HVHDF effluent rate was 208 (146.3-298.3) ml/kg/h. A final two-compartment population PK model predicted mean (%SE) total piperacillin clearance on HVHDF was 6.9 (6.4) l/h, volume of distribution of central compartment 9.0 (10.1) l and of peripheral compartment 11.2 (12.2) l. The PTA of 50% fT>MIC for piperacillin 4 g/tazobactam 0.5 g dosed every 8 h as 0.5-h and 4-h infusion was 84.3% and 100% for MIC of 16 mg/l respectively. Aiming 100% fT>MIC of 16 mg/l, the PTA values were 88.6% and 61.0%, for piperacillin 4 g/tazobactam 0.5 g 4-h infusion every 6 and 8 h respectively., Conclusions: For bactericidal PK/PD target attainment piperacillin/tazobactam doses of 4/0.5 g every 8 h appear appropriate in septic shock patients with minimal residual renal function during HVHDF., (© 2015 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Neuromuscular electrical stimulation (NMES) is an established method for functional restoration of muscle function, rehabilitation, and diagnostics. In this work, NMES was applied with surface electrodes placed on the anterior thigh to identify the main differences between current-controlled (CC) and voltage-controlled (VC) modes. Measurements of the evoked knee extension force and the myoelectric signal of quadriceps and hamstrings were taken during stimulation with different amplitudes, pulse widths, and stimulation techniques. The stimulation pulses were rectangular and symmetric biphasic for both stimulation modes. The electrode-tissue impedance influences the differences between CC and VC stimulation. The main difference is that for CC stimulation, variation of pulse width and amplitude influences the amount of nerve depolarization, whereas VC stimulation is only dependent on amplitude variations for pulse widths longer than 150 μs. An important remark is that these findings are strongly dependent on the characteristics of the electrode-skin interface. In our case, we used large stimulation electrodes placed on the anterior thigh, which cause higher capacitive effects. The controllability, voltage compliance, and charge characteristics of each stimulation technique should be considered during the stimulators design. For applications that require the activation of a large amount of nerve fibers, VC is a more suitable option. In contrast, if the application requires a high controllability, then CC should be chosen prior to VC., (Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

The level of sustainable excitability within lumbar spinal cord circuitries is one of the factors determining the functional outcome of locomotor therapy after motor-incomplete spinal cord injury. Here, we present initial data using noninvasive transcutaneous lumbar spinal cord stimulation (tSCS) to modulate this central state of excitability during voluntary treadmill stepping in three motor-incomplete spinal cord-injured individuals. Stimulation was applied at 30 Hz with an intensity that generated tingling sensations in the lower limb dermatomes, yet without producing muscle reflex activity. This stimulation changed muscle activation, gait kinematics, and the amount of manual assistance required from the therapists to maintain stepping with some interindividual differences. The effect on motor outputs during treadmill-stepping was essentially augmentative and step-phase dependent despite the invariant tonic stimulation. The most consistent modification was found in the gait kinematics, with the hip flexion during swing increased by 11.3° ± 5.6° across all subjects. This preliminary work suggests that tSCS provides for a background increase in activation of the lumbar spinal locomotor circuitry that has partially lost its descending drive. Voluntary inputs and step-related feedback build upon the stimulation-induced increased state of excitability in the generation of locomotor activity. Thus, tSCS essentially works as an electrical neuroprosthesis augmenting remaining motor control., (Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

A stimulator for neuromuscular electrical stimulation (NMES) was designed, especially suiting the requirements of elderly people with reduced cognitive abilities and diminished fine motor skills. The aging of skeletal muscle is characterized by a progressive decline in muscle mass, force, and condition. Muscle training with NMES reduces the degradation process. The discussed system is intended for evoked muscle training of the anterior and posterior thigh. The core of the stimulator is based on a microcontroller with two modular output stages. The system has two charge-balanced biphasic voltage-controlled stimulation channels. Additionally, the evoked myoelectric signal (M-wave) and the myokinematic signal (surface acceleration) are measured. A central controller unit allows using the stimulator as a stand-alone device. To set up the training sequences and to evaluate the compliance data, a personal computer is connected to the stimulator via a universal serial bus. To help elderly people handle the stimulator by themselves, the user interface is kept very simple. For safety reasons, the electrode impedance is monitored during stimulation. A comprehensive compliance management with included measurements of muscle activity and stimulation intensity enables a scientific use of the stimulator in clinical trials., (© 2011, Copyright the Authors. Artificial Organs © 2011, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Muscle tissue composition accounting for the relative content of muscle fibers and intramuscular adipose and loose fibrous tissues can be efficiently analyzed and quantified using images from spiral computed tomography (S-CT) technology and the associated distribution of Hounsfield unit (HU) values. Muscle density distribution, especially when including the whole muscle volume, provides remarkable information on the muscle condition. Different physiological and pathological scenarios can be depicted using the muscle characterization technique based on the HU values and the definition of appropriate intervals and the association of such intervals to different colors. Using this method atrophy, degeneration, and restoration in denervated muscle undergoing electrical stimulation treatments can be clearly displayed and monitored. Moreover, finite element methods are employed to calculate Young's modulus on the patella bone and to analyze correlation between muscle contraction and bone strength changes. The reliability of this tool though depends on S-CT assessment and calibration. To assess imaging quality and the use of HU values to display muscle composition, different S-CT devices are compared using a Quasar body scanner. Density distributions and volumes of various calibration elements such as lung, polyethylene, water equivalent, and trabecular and dense bone are measured with different scanning protocols and at different points of time. The results show that every scanned element undergoes HU variations, which are greater for materials at the extremes of the HU scale, such as dense bone and lung inhale. Moreover, S-CT scanning with low tube voltages (80 KV) produces inaccurate HU values especially in bones. In conclusion, 3-D modeling techniques based on S-CT scanning is a powerful follow-up tool that may provide structural information at the millimeter scale, and thus may drive choice and timing to validate rehabilitation protocols., (© 2011, Copyright the Authors. Artificial Organs © 2011, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Background: Gastrointestinal (GI) problems are not uniformly assessed in intensive care unit (ICU) patients and respective data in available literature are insufficient. We aimed to describe the prevalence, risk factors and importance of different GI symptoms., Methods: We prospectively studied all patients hospitalized to the General ICU of Tartu University Hospital in 2004-2007., Results: Of 1374 patients, 62 were excluded due to missing data. Seven hundred and seventy-five (59.1%) patients had at least one GI symptom at least during 1 day of their stay, while 475 (36.2%) suffered from more than one symptom. Absent or abnormal bowel sounds were documented in 542 patients (41.3%), vomiting/regurgitation in 501 (38.2%), high gastric aspirate volume in 298 (22.7%), diarrhoea in 184 (14.0%), bowel distension in 139 (10.6%) and GI bleeding in 97 (7.4%) patients during their ICU stay. Absent or abnormal bowel sounds and GI bleeding were associated with significantly higher mortality. The number of simultaneous GI symptoms was an independent risk factor for ICU mortality. The ICU length of stay and mortality of patients who had two or more GI symptoms simultaneously were significantly higher than in patients with a maximum of one GI symptom., Conclusion: GI symptoms occur frequently in ICU patients. Absence of bowel sounds and GI bleeding are associated with impaired outcome. Prevalence of GI symptoms at the first day in ICU predicts the mortality of the patients.

Functional electrical stimulation (FES) of long-term denervated, degenerated human skeletal muscle has proven to be a suitable method for improving a number of physiological parameters. The underlying mechanisms of activation of a denervated muscle fiber can be described with suitably modified and extended Hodgin-Huxley type models, coupled with three-dimensional (3D) finite element models of the surrounding electrical field. Regions of activation within a muscle can be determined using a 3D computer model. However, simulation results have not yet been validated experimentally. During and immediately after exercise, muscle shows increased T2-relaxation times. It is thus possible to estimate muscle activation noninvasively and spatially resolved with the magnetic resonance imaging (MRI) method of T2 mapping, which was, therefore, chosen as a suitable validation approach. Six patients were scanned prior to FES training with a multislice multiecho MSME-sequence at 3 Tesla and then asked to perform one of their regular daily training-sessions (leg extensions). Subjects were then repositioned in the MR-scanner and two to five postexercise scans were recorded. Pre- and postexercise scans were coregistered and T2-parameter maps were calculated. Regions of interest (ROIs) were drawn manually around quadriceps femoris and its antagonists. Activation was detected in all patients. In well-trained patients, activation in the quadriceps was found to be considerably higher than in its antagonists. These experimental results will help further improve existing models of FES of denervated degenerated human skeletal muscle.

Objective: Juvenile idiopathic arthritis (JIA) is an autoimmune disease of the young. The pathogenesis is not completely understood. Premature aging, associated thymic involution, and compensatory autoproliferation could play important roles in the pathogenesis of autoimmunity. We undertook this study to determine whether patients with JIA demonstrate premature immunosenescence., Methods: To test this hypothesis, we measured 3 indicators of aging: the percentages and total counts of peripheral blood naive T cells, the frequency of T cell receptor excision circles (TRECs) in naive T cells, and telomeric erosion and Ki-67 expression as estimates of the replicative history of homeostatic proliferation., Results: JIA patients showed an accelerated loss of CD4+,CD45RA+,CD62L+ naive T cells with advancing age and a compensatory increase in the number of CD4+,CD45RO+ memory T cells. JIA patients demonstrated a significantly decreased frequency of TRECs in CD4+,CD45RA+ naive T cells compared with age-matched healthy donors (P = 0.002). TREC numbers correlated with age only in healthy donors (P = 0.0001). Telomeric erosion in CD4+,CD45RA+ naive T cells was increased in JIA patients (P = 0.01). The percentages of Ki-67-positive CD4+,CD45RA+ naive T cells were increased in JIA patients (P = 0.001) and correlated with disease duration (P = 0.003), which was also an independent factor contributing to telomeric erosion (P = 0.04)., Conclusion: Our findings suggest that age-inappropriate T cell senescence and disturbed T cell homeostasis may contribute to the development of JIA. In patients with JIA, dysfunction in the ability to reconstitute the T cell compartment should be considered when exploring new therapeutic strategies.

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.

The pendulum test was applied to evaluate functional electrical stimulation (FES)-induced joint moments in paraplegics with denervated muscles. Therefore a manipulandum was connected to the knee joint and programmed to elicit gravity-induced leg oscillations. The FES-induced output torque was compensated for in order to keep the leg in a mean vertical position (knee angle 90 degrees ). A second-order dynamical model was applied to extract the elastic and viscous moments from the recorded leg oscillations. This model provided an almost adequate description of the relaxed and FES-contracted states. In the relaxed state the elastic moment was 15.3 +/- 2.37 Nm/rad and the viscous moment was 0.41 +/- 0.21 Nms/rad. The FES-induced elastic moment was 29.4 +/- 28.5 Nm/rad and the FES-induced viscous moment was 1.53 +/- 1.03 Nms/rad (N = 10, before FES-training).

Features of the human spinal cord motor control are described using two spinal cord injury models: (i) the spinal cord completely separated from brain motor structures by accidental injury; (ii) the spinal cord receiving reduced and altered supraspinal input due to an incomplete lesion. Systematic studies using surface electrode polyelectromyography were carried out to assess skeletal muscle reflex responses to single and repetitve stimulation in a large number of subjects. In complete spinal cord injured subjects the functional integrity of three different neuronal circuits below the lesion level is demonstrated: first, simple mono- and oligosynaptic reflex arcs and polysynaptic pathways; second, propriospinal interneuron system with their cell in the gray matter and the axons in the white matter of the spinal cord conducting activity between different spinal cord segments; and third, internuncial gray matter neurons with short axons and dense neuron contact within the spinal gray matter. All of these three systems participate continuously in the generation of spinal cord reflex output activating muscles. The integration of these systems and their relative degree of excitation and set-up produces characteristic functions of motor control. In incomplete spinal cord injured patients, the implementation of brain motor control depends on the profile of residual brain descending input and its integration with the functional neuronal circuits below the lesion. Locomotor patterns result from the establishment of a new structural relationship between brain and spinal cord. The functions of this new structural relationship are expressed as an alternative, but characteristic and consistent neurocontrol. The more we know about how the brain governs spinal cord networks, the better we can describe human motor control. On the other hand such knowledge is essential for the restoration of residual functions and for the construction of new cord circuitry to expand the functions of the injured spinal cord.

Morphologic characteristics of the long-term denervated muscle in animals suggest that some original fibers are lost and some of those seen are the result of repeated cycles of fiber regeneration. Muscle biopsies from lower motoneuron denervated patients enrolled in the EU Project RISE show the characteristics of long-term denervation. They present a few atrophic or severely atrophic myofibers dispersed among adipocytes and connective tissue (denervated degenerated muscle, DDM). Monoclonal antibody for embryonic myosin shows that regenerative events are present from 1- to 37-years postspinal cord injury (SCI). After 2- to 10-years FES-training the muscle cryosections present mainly large round myofibers. In the FES-trained muscles the regenerative events are present, but at a lower rate than long-term denervated muscles (myofiber per mm2 of cryosection area: 0.8 +/- 1.3 in FES vs. 2.3 +/- 2.3 in DDM, mean +/- SD, P = 0.011). In our opinion this is a sound additional evidence of effectiveness of the Kern's electrical stimulation protocol for FES of DDM. In any case, the overall results demonstrate that the FES-training is safe: at least it does not induce more myofiber damage/regeneration than denervation per se.

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.

Measurements of the rheobase and chronaxie can be used to define the excitability of nerves and muscles. The aim of this study was to obtain a record over many weeks of changes in the rheobase and chronaxie of denervated rabbit tibialis anterior muscle (TA). A custom-built electronic stimulator was implanted into the peritoneal cavity of New Zealand White rabbits. Large stainless steel electrodes were placed on the denervated TA muscle. Rheobase and chronaxie were measured noninvasively at weekly intervals by means of a laptop PC, which communicated with the stimulator via a radio-frequency link. At each setting the denervated TA was palpated manually to detect the response of the muscle. During the first few days after denervation the rheobase increased transiently to 0.8 +/- 0.13 mA, approximately twice the value for normal innervated muscle, then decreased to normal for the remainder of the experimental period. Chronaxie underwent a significant 3-fold increase from 4.5 +/- 1.1 ms to 14.1 +/- 1.1 ms during the first two weeks of denervation and remained elevated throughout. The custom-built implantable electronic stimulator allowed changes in muscle excitability to be studied over a long period of denervation within individual animals, providing an accurate assessment of the time course of denervation-induced changes in muscle excitability.

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.

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.

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.

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.

The use of electrical stimulation for denervated muscles is still considered to be a controversial issue by many rehabilitation facilities and medical professionals because prior clinical experience has shown that treating denervated muscle tissue using exponential current over a long time period constitutes an impossible task. Despite this fact, we managed to evoke tetanic contractions in denervated muscle using a long duration stimulation with anatomically shaped electrodes and sufficiently high amplitudes. The pulse amplitudes, which were being used for this purpose, exceeded by far the MED-GV and EC regulations (300 mJ/impulse). For this reason, an application has recently been submitted to have the EC regulations changed accordingly. It takes a tetanic contraction to achieve the desired muscle fiber tension, constituting a hypertrophic stimulus. It is also an appropriate means of exercise, which is capable of creating the metabolic and structural conditions needed (e.g, increased mitochondrial volume and capillary density) to obtain satisfactory muscle performance. With patients suffering from a complete spinal cord injury at level D12/L1, having motor and sensory loss in both lower extremities, we were able to train denervated muscle using long-duration stimulation, evoking single muscle contractions at first, soon followed by tetanic contractions against gravity. To increase the efficacy of this functional electrical stimulation (FES) strengthening program, we used ankle weights. With daily FES training over a period of 1-2 years, denervated muscle was exercised until it produced torques between 16 and 38 Nm in the m. quadriceps. With that muscle force, it is possible to stand up from a sitting position in parallel bars. Our results show that denervated muscle in humans is indeed trainable and can perform functional activities with FES. Furthermore, this method of stimulation can assist in decubitus prevention and significantly improve the mobility of paraplegics.

Today functional electrical stimulation (FES) is used among other treatments to restore hand and arm function, to restore mobility of the lower extremities, for phrenic pacing, and in cardiomyoplasty. Common to all FES applications is that they require careful setup of stimulation parameters. To improve these tasks, personal computer (PC) based software for stimulation parameter evaluation and data acquisition was written. First, the described software was used to mobilize paraplegic patients in conjunction with an 12C bus controlled 8 channel surface stimulator. Electrodes were placed on each leg on the m. quadriceps and m. gluteus for hip and knee extension and the peroneal nerve to elicit flexion reflex. The fourth channel was used to correspond to subjects' individual needs. The stimulation patterns for standing up, walking, and sitting down easily could be set up and optimized by adjusting up to 128 stimulation parameters in a task-specific way.

We are reporting on the clinical and physiological effects of 8 months of functional electrical stimulation (FES) of the quadriceps femoris muscle on 10 paraplegic patients. Each patient had muscle biopsies, computed tomography (CT) muscle diameter measurements, and knee extension strength testing both before and after 8 months of FES training. Skin perfusion was documented through infrared telethermography and xenon clearance; muscle perfusion was recorded through thallium scintigraphy. After 8 months of FES training, the baseline skin perfusion showed an 86% increase; muscle perfusion was augmented by 87%. Muscle fiber diameters showed an average increase of 59% after 8 months of FES training. Muscles in patients with spastic paresis showed an increase in aerobic and anaerobic muscle enzymes up to the normal range of healthy humans. The increment in muscle area, as visible on CT scans of the quadriceps femoris muscle, was 30%. Using FES, we were able to improve metabolism and to induce positive trophic changes in our patients' lower extremities. In spastic paraplegics, rising and walking achieved through FES are much better training than FES ergometer training. Larger muscle masses are activated, and the heart rate is increased; therefore, the impact on cardiovascular fitness and metabolism is much greater. This effectively addresses and prevents the problems that result from inactivity in paraplegic patients.

Transcutaneous electrical stimulation of the quadriceps femoris muscle was applied in 14 paraplegic patients (10 spastic patients with spinal cord lesions and 4 patients with conus-cauda lesions with denervation atrophy). In both the spastic and the denervated group, the vastus lateralis muscle was biopsied and computed tomography (CT) images of the entire upper leg were made both at the onset and termination of the 8-month training period. The stimulation was carried out twice a day for 20 min. The increase in muscle tissue was significant in the CT images. The biopsies showed that the fiber diameter of both fiber types increased during the training period in the spastic group from 47 to 67 microns and in the denervated group from 22 to 38 microns. In both groups, the differences were significant between the first and second biopsies. Both groups showed a marked Type 2 fiber predominance. The histological and CT findings correlated with the clinical improvement of muscle function.