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Biomedical subjects

R B Stein

Publications and source records attributed to R B Stein.

At least 37 records · Page 2Linked to original sources

Minimizing discomfort with surface neuromuscular stimulation.

The purpose of this study was to evaluate the effects of stimulus parameters, electrode types, and electrode positions on the perception of discomfort during lower extremity surface neuromuscular stimulation. Ten normal and eight neurologically impaired (four incomplete spinal cord and four stroke) subjects were enrolled. Neurologically impaired subjects had some sensation, although it was often reduced. Parameters of the stimulation were varied in a way that produced the same level of ankle dorsiflexion, as measured with a goniometer. Discomfort was assessed after each stimulation with a 0-10 verbal scale (0, no discomfort; 10, worst pain). Increasing the pulse frequency was associated with increased discomfort for subjects in both groups (p > 0.05). Increasing the pulse duration was associated with increased discomfort in the neurologically impaired subjects (p > 0.05), but not in the normal subjects (p > 0.05). The electrode size and type had no effects on discomfort (p > 0.05). Stimulation of the peroneal nerve over the fibular head was better tolerated than the direct motor point stimulation of the tibialis anterior motor point (p < 0.05). The data suggest that to minimize discomfort, surface stimulation should be applied over nerves rather than motor points, and frequency and pulse duration should be set as low as possible for a given degree of contraction.

Adult↗

Comparative tolerability of treatments for inflammatory bowel disease.

Despite limited understanding of therapeutic aetiopathogenesis of ulcerative colitis and Crohn's disease, there is a strong evidence base for the efficacy of pharmacological and biological therapies. It is equally important to recognise toxicity of the medical armamentarium for inflammatory bowel disease (IBD). Sulfasalazine consists of sulfapyridine linked to 5-aminosalicylic acid (5-ASA) via an azo bond. Common adverse effects related to sulfapyridine 'intolerance' include headache, nausea, anorexia, and malaise. Other allergic or toxic adverse effects include fever, rash, haemolytic anaemia, hepatitis, pancreatitis, paradoxical worsening of colitis, and reversible sperm abnormalities. The newer 5-ASA agents were developed to deliver the active ingredient of sulfasalazine while minimising adverse effects. Adverse effects are infrequent but may include nausea, dyspepsia and headache. Olsalazine may cause a secretory diarrhoea. Uncommon hypersensitivity reactions, including worsening of colitis, pancreatitis, pericarditis and nephritis, have also been reported. Corticosteroids are commonly prescribed for treatment of moderate to severe IBD. Despite short term efficacy, corticosteroids have numerous adverse effects that preclude their long term use. Adverse effects include acne, fluid retention, fat redistribution, hypertension, hyperglycaemia, psycho-neurological disturbances, cataracts, adrenal suppression, growth failure in children, and osteonecrosis. Newer corticosteroid preparations offer potential for targeted therapy and less corticosteroid-related adverse effects. Azathioprine and mercaptopurine are associated with pancreatitis in 3 to 15% of patients that resolves upon drug cessation. Bone marrow suppression is dose related and may be delayed. The adverse effects of methotrexate include nausea, leucopenia and, rarely, hypersensitivity pneumonia or hepatic fibrosis. Common adverse effects of cyclosporin include nephrotoxicity, hypertension, headache, gingival hyperplasia, hyperkalaemia, paresthesias, and tremors. These adverse effects usually abate with dose reduction or cessation of therapy. Seizures and opportunistic infections have also been reported. Antibacterials are commonly employed as primary therapy for Crohn's disease. Common adverse effects of metronidazole include nausea and a metallic taste. Peripheral neuropathy can occur with prolonged administration. Ciprofloxacin and other antibacterials may be beneficial in those intolerant to metronidazole. Newer immunosuppressive agents previously reserved for transplant recipients are under investigation for IBD. Tacrolimus has an adverse effect profile similar to cyclosporin, and may cause renal insufficiency. Mycophenolate mofetil, a purine synthesis inhibitor, has primarily gastrointestinal adverse effects. Biological agents targeting specific sites in the immunoinflammatory cascade are now available to treat IBD. Infliximab, a chimeric antibody targeting tumour necrosis factor-or has been well tolerated in clinical trials and early postmarketing experience. Additional trials are needed to assess long term adverse effects.

Adrenal Cortex Hormones↗

Complications after ileal pouch-anal anastomosis.

Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is currently the procedure of choice for ulcerative colitis patients who require colectomy. Despite its wide acceptance, a variety of long-term complications of the procedure exist that can be severe and even lead to pouch excision. Pouchitis occurs in up to one half of patients after IPAA, but is usually well controlled with medical therapy. A small percentage of patients develop chronic persistent pouchitis, which often requires long-term medical therapy and may result in pouch failure. Fistulas and strictures can also complicate the pouch procedure. In general, patients with Crohn's disease are not usually offered IPAA, because recurrence of disease, fistulas, abscesses, and strictures may lead to a higher incidence of pouch failure. Some ulcerative colitis patients develop complications after IPAA and are subsequently diagnosed with Crohn's disease. These patients may develop refractory fistulas, strictures, and extraintestinal manifestations of inflammatory bowel disease. Neoplastic transformation of the pelvic pouch has also been reported, particularly in patients with chronic pouchitis. Thorough follow-up and endoscopic surveillance with biopsies of the ileal pouch are therefore recommended.

Anastomosis, Surgical↗

Interaction of the Jendrássik maneuver with segmental presynaptic inhibition.

Since its initial description in 1883, the Jendrássik maneuver (JM) has been used in clinical neurological practice as an effective means of potentiating the tendon tap in neurologically impaired patients. The JM also potentiates its electrical analogue, the Hoffman (H-) reflex, but the mechanism of the reflex modulation has not been clearly established. We studied soleus H-reflex modulation in neurologically intact subjects while at rest and during a mild plantarflexion contraction (EMG level equivalent to approximately 10% maximum voluntary contraction). The control H-reflex was elicited by stimulating the tibial nerve in the popliteal fossa with single pulses of 1 ms duration. Conditioning of the reflex was by: (1) increasing segmental presynaptic inhibition via common peroneal nerve (CP) stimulation; (2) pulling the arms and clenching the teeth (JM); or (3) applying both together (JM+CP). CP stimulation significantly (P<0.05) suppressed the H-reflex (50% Hmax), while JM significantly (P<0.05) facilitated it during contraction. From either an analysis of the grouped data or by a within-subject analysis, we found that the combined effect of stimulating JM+CP was significantly lower than JM alone, but did not differ from control values or from CP alone. The simplest mechanism would be that the effects of the two sum algebraically on the interneurones producing segmental presynaptic inhibition of the H-reflex.

Adult↗

Effects of inhibitory neurotransmitters on the mudpuppy (Necturus maculatus) locomotor pattern in vitro.

Effects of inhibitory neurotransmitters on the locomotor rhythm and pattern generation were investigated using an in vitro preparation isolated from the mudpuppy (Necturus maculatus). The preparation consisted of the first five segments of the spinal cord and the right forelimb attached by the brachial nerves. During N-methyl-d-aspartate (NMDA)-induced locomotion, the rhythmic motor output (EMG) was recorded unilaterally from elbow flexor and extensor muscles. While neither glycine nor gamma-aminobutyric acid (GABA)-related substances induced locomotion in the absence of NMDA, they modulated NMDA-induced locomotion. Bath application of glycine and GABA suppressed the rhythmic motor pattern induced by NMDA. Addition of glycine receptor antagonist strychnine or GABA(A) receptor antagonist bicuculline disrupted the phase relationship between antagonistic motor pools during ongoing locomotion, thereby changing the normal alternating pattern into synchronous EMG bursts. Both the GABA(A) receptor agonist muscimol and GABA(B) receptor agonist baclofen mimicked the effects of GABA as they either slowed down or stopped locomotion. Nipecotic acid, a GABA uptake blocker, had a similar effect. This suggested that an endogenous release of GABA modulated the locomotor rhythm. The endogenous release was antagonized by the GABA(A) and GABA(B) receptor antagonists bicuculline and CGP-35348, respectively. Immunocytochemistry revealed that glycine and GABA-positive neurons and fibers were present in mudpuppy spinal cord. Although the GABAergic neurons were more numerous than glycinergic neurons, both cell types contributed processes directed towards the white matter and occasionally towards the ependymal lining of the central canal. Our results suggest that inhibitory neurotransmitters exert powerful actions upon the neuronal network governing forelimb locomotion in the mudpuppy. The effects we observed may be mediated by a network of segmentally distributed glycinergic and GABAergic spinal neurons.

Animals↗

Multicenter evaluation of electrical stimulation systems for walking.

OBJECTIVE: To test the long-term benefits of several noninvasive systems for functional electrical stimulation (FES) during walking. DESIGN: Forty subjects (average years since injury, 5.4) were studied in four centers for an average time of 1 year. Gait parameters were tested for all subjects with and without FES. Thus, subjects served as their own controls, since the specific effect of using FES could be separated from improvements resulting from other factors (e.g., training). SETTING: Subjects used the devices in the community, but were tested in a university or hospital setting. PATIENTS: Subjects with spinal cord injury (n = 31) were compared to subjects with cerebral damage (n = 9). MAIN OUTCOME MEASURES: Gait parameters (speed, cycle time, stride length). Acceptance was studied by means of a questionnaire. RESULTS: Some initial improvement in walking speed (average increase of >20%) occurred, and continuing gains were seen (average total improvement, 45%). The largest relative gains were seen in the slowest walkers (speeds of <0.3 m/sec). Acceptance of the FES systems was good and improved systems have been developed using feedback from the subjects. CONCLUSIONS: Based on the improvements in speed and the acceptance of these FES systems, a greatly increased role for FES in treating gait disorders is suggested.

Adolescent↗

Biomechanics of human quadriceps muscles during electrical stimulation.

The quadriceps muscles of neurologically intact and spinal cord injured (SCI) human subjects were stimulated with constant current pulses. Up to three, separately adjustable stimulating electrodes over the motor points for vastus medialis (VM), vastus lateralis (VL) and rectus femoris (RF) muscles were used to maximize torque generation while minimizing discomfort. The torque generated by stimulation increased as the knee was slowly flexed to about 1 rad (50-60 degrees) and decreased beyond that point (a 'negative slope' on a torque-angle curve). Despite this region of negative slope the force generated by small oscillations remained positively correlated to the angle changes. When the knee was slowly extended again from a flexed position, the torque continued to decline and therefore showed a large degree of 'hysteresis'. Of the three heads studied, only stimulation of RF muscle generally produced this behavior. VL and VM had torques that increased monotonically with knee flexion over the range studied. The torques generated with electrical stimulation of normal subjects represented up to about 30% of maximum voluntary contraction. When subjects generated similar torques voluntarily, the negative slope region and substantial hysteresis were not observed. Thus, SCI subjects may be adversely affected by hysteresis during electrically-induced transitions from sitting to standing and vice versa, while normal subjects are not.

Adult↗

What functions do reflexes serve during human locomotion?

Studies on the reflex modulation of vertebrate locomotion have been conducted in many different laboratories and with many different preparations: for example, lamprey swimming, bird flight, quadrupedal walking in cats and bipedal walking in humans. Emerging concepts are that reflexes are task-, phase- and context-dependent. To function usefully in a behaviour such as locomotion wherein initial conditions change from step to step, reflexes would have to show modulation. Papers are reviewed in which the study of different reflexes have been conducted during different behaviours, with an emphasis on experiments in humans. A framework is developed in which the modulation and flexibility of reflexes are demonstrated. Alterations in cutaneous, and muscle (stretch and load receptor) reflexes between sitting, standing and walking are discussed. Studies in which both electrical, mechanical and 'natural' receptor activation have been conducted during walking are reviewed. Reflexes are shown to have important regulatory functions during human locomotion. A framework for discussion of reflex function throughout the step cycle is developed. The function of a given reflex pathway changes dynamically throughout the locomotor cycle. While all reflexes act in concert to a certain extent, generally cutaneous reflexes act to alter swing limb trajectory to avoid stumbling and falling. Stretch reflexes act to stabilize limb trajectory and assist force production during stance. Load receptor reflexes are shown to have an effect on both stance phase body weight support and step cycle timing. After neurotrauma or in disease, reflexes no longer function as during normal locomotion, but still have the potential to be clinically exploited in gait modification regimens.

Animals↗

Medical therapy for inflammatory bowel disease.

CD and UC represent a spectrum of chronic IBD that present in protean ways and are accompanied by a variety of systemic sequelae. Sulfasalazine and the newer 5-aminosalicylates are important in the management of mild-to-moderate disease, whereas corticosteroids remain the primary therapy for most patients with moderate-to-severe disease (Tables 2-5). The toxicities associated with long-term steroid therapy, combined with their ineffectiveness as maintenance medications, have led to increased use of immunomodulators, such as azathioprine and 6-MP, for the treatment of steroid-dependent and steroid-resistant IBD. Infliximab is a novel therapeutic adjunct for chronically active and fistulizing CD that will herald a new era of biologic therapy for IBD. Meanwhile, CSA remains an alternative to urgent colectomy in severe UC unresponsive to corticosteroids and also for CD patients with severe disease or refractory fistulas. Finally, continued insights into the etiopathogenic pathways in IBD will provide evolving and innovative approaches until the eventual causes and cures are elucidated. In the meantime, clinicians should remain optimistic regarding current ability to reduce the morbidity and maintain the quality of life for patients suffering with these frustrating diseases.

Acute Disease↗

Functional electrical stimulation after spinal cord injury.

This article reviews work mainly from my own laboratory on the effects of electrical stimulation for therapy and function following spinal cord injury. One to two hours per day of intermittent stimulation can increase muscle strength and endurance and also reverse some of the osteoporosis in bones that are stressed by the stimulation. Stimulation during walking can also be used to improve speed and other parameters of the gait. Surface stimulation systems with 1-4 channels of stimulation were used in a multicenter study. Initial increases of almost 20% in walking speed were seen and overall increases of nearly 50% in subjects who continued to receive stimulation for a year on average. Some changes were due to improved strength and coordination with stimulation and additional walking, but a specific effect of stimulation persisted throughout the trial. Improved devices will soon be available commercially that were developed on the basis of feedback from users.

Electric Stimulation↗

Nutrition in inflammatory bowel disease.

Clinical and basic research continues to expand our understanding of the complex pathogenesis of inflammatory bowel diseases. The potential roles played by fatty acid intake, serum leptin, and nitric oxide in the promotion of intestinal inflammation in Crohn's disease and ulcerative colitis will be reviewed. In addition, important advances in the areas of bone disease, vitamin deficiency, growth failure, and home parenteral nutrition will be discussed.

Adult↗

Identification of electrically stimulated quadriceps muscles in paraplegic subjects.

This work establishes a method for the noninvasive in vivo identification of parametric models of electrically stimulated muscle in paralyzed individuals, when significant inertial loads and/or load transitions are present. The method used differs from earlier work, in that both the pulse width and stimulus period (interpulse interval) modulation are considered. A Hill-type time series model, in which the output is the product of two factors (activation and torque-angle) is used. In this coupled model, the activation dynamics depend upon velocity. Sequential nonlinear least squares methods are used in the parameter identification. The ability of the model, using identified time-varying parameters, to accurately predict muscle torque outputs is evaluated, along with the variability of the identified parameters. This technique can be used to determine muscle parameter models for biomechanical computer simulations, and for real-time adaptive control and monitoring of muscle response variations such as fatigue.

Algorithms↗

Characterization of signals and noise rejection with bipolar longitudinal intrafascicular electrodes.

Longitudinal intrafascicular electrodes (LIFE's) are fine electrodes threaded into the extracellular space between axons in peripheral nerves or spinal roots. We are developing these electrodes for application in functional electrical stimulation and in basic physiology. An area of concern in chronic recording application of LIFE's is the possibility of electromyogram and other external noise sources masking the recorded neural signals. We characterized neural signals recorded by LIFE's and confirmed by three independent methods that increasing interelectrode spacing for bipolar LIFE's increases signal amplitude. The spectrum of neural signal from bipolar and monopolar LIFE lies between 300 Hz and 10 kHz. The amplitude of the spectrum increases with increasing interelectrode spacing, although the distribution is not affected. Single unit analysis of LIFE recordings show that they record selectively from units closest to the electrode active site. Units with conduction velocities ranging from 50-120 m/s were identified. Extraneural noise, as stimulus artifact or electromyogram, is much reduced with bipolar LIFE recording, as compared to monopolar recordings. Relative improvement in neural signal to extraneural noise increases with interelectrode spacing up to about 2 mm. Since there is no further improvement beyond 2 mm, we conclude that the preferred interelectrode spacing for bipolar LIFE's is 2 mm.

Animals↗

Optimal control of walking with functional electrical stimulation: a computer simulation study.

Bipedal locomotion was simulated to generate a pattern of activating muscles for walking using electrical stimulation in persons with spinal cord injury (SCI) or stroke. The simulation presented in this study starts from a model of the body determined with user-specific parameters, individualized with respect to the lengths, masses, inertia, muscle and joint properties. The trajectory used for simulation was recorded from an able-bodied subject while walking with ankle-foot orthoses. A discrete mathematical model and dynamic programming were used to determine the optimal control. A cost function was selected as the sum of the squares of the tracking errors from the desired trajectories, and the weighted sum of the squares of agonist and antagonist activations of the muscle groups acting around the hip and knee joints. The aim of the simulation was to study plausible trajectories keeping in mind the limitations imposed by the spinal cord injury or stroke (e.g., spasticity, decreased range of movements in some joints, limited strength of paralyzed, externally activated muscles). If the muscles were capable of generating the movements required and the trajectory was achieved, then the simulation provided two kinds of information: 1) timing of the onset and offset of muscle activations with respect to the various gait events and 2) patterns of activation with respect to the maximum activation. These results are important for synthesizing a rule-based controller.

Algorithms↗

Modulation of stretch reflexes during imposed walking movements of the human ankle.

Our overall objectives were to examine the role of peripheral afferents from the ankle in modulating stretch reflexes during imposed walking movements and to assess the mechanical consequences of this reflex activity. Specifically we sought to define the changes in the electromyographic (EMG) and mechanical responses to a stretch as a function of the phase of the step cycle. We recorded the ankle position of a normal subject walking on a treadmill at 3 km/h and used a hydraulic actuator to impose the same movements on supine subjects generating a constant level of ankle torque. Small pulse displacements, superimposed on the simulated walking movement, evoked stretch reflexes at different phases of the cycle. Three major findings resulted: 1) soleus reflex EMG responses were influenced strongly by imposed walking movements. The response amplitude was substantially smaller than that observed during steady-state conditions and was modulated throughout the step cycle. This modulation was qualitatively similar to that observed during active walking. Because central factors were held constant during the imposed walking experiments, we conclude that peripheral mechanisms were capable of both reducing the amplitude of the reflex EMG and producing its modulation throughout the movement. 2) Pulse disturbances applied from early to midstance of the imposed walking cycle generated large reflex torques, suggesting that the stretch reflex could help to resist unexpected perturbations during this phase of walking. In contrast, pulses applied during late stance and swing phase generated little reflex torque. 3) Reflex EMG and reflex torque were modulated differently throughout the imposed walking cycle. In fact, at the time when the reflex EMG response was largest, the corresponding reflex torque was negligible. Thus movement not only changes the reflex EMG but greatly modifies the mechanical output that results.

Adult↗

Turning strategies during human walking.

The mechanisms involved in rapidly turning during human walking were studied. Subjects were asked to walk at a comfortable speed and to turn toward the instructed direction as soon as they felt an electrical stimulus to the superficial peroneal nerve. Stimuli were presented repeatedly at random over 10- to 15-min periods of walking for turning in both directions. Electromyograms (EMGs), joint angular movements of the right leg, and forces under both feet were recorded. The step cycle was divided into 16 parts, and the responses to stimuli in each part were analyzed separately. Two turning strategies were used, depending on which leg was placed in front for braking. For example, to turn to the right when the right foot was placed in front, subjects generally altered direction by spinning the body around the right foot (spin turn). To turn left when the right foot was in front, subjects shifted weight to the right leg, externally rotated the left hip, stepped onto the left leg, and continued turning until the right leg stepped in the new direction (step turn). The step turn is easy and stable because the base of support during the turn is much wider than in the spin turn, so some subjects used it in all parts of the cycle. Initially, the deceleration of walking is similar to a rapid stopping task, which has been previously examined. The deceleration mechanism involves a sequence of distal-to-proximal activation of muscles on one side of the body (soleus, biceps femoris, and erector spinae). This pattern is similar to the "ankle strategy" used in postural control during forward sway. The control of foot placement in the swing leg and muscle activities for rotating the trunk in the stance leg occurred within a step after the cue. The action of ankle inverters and elevation of the pelvis by activity of gluteus medius may contribute to the control of trunk rotation. This activity was closely related to the timing of the opposite foot strike, independent of the part of the step cycle when the stimulus was applied. In most subjects, the turn was completed without resetting the underlying walking rhythm. This first EMG analysis of rapid turning shows how common strategies for postural sway and stopping can be combined with one of two turning strategies. This simplifies the complex task of turning at a random time in the step cycle.

Adult↗