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Biomedical subjects

D Burke

Publications and source records attributed to D Burke.

At least 19 recordsLinked to original sources

Limitations of laser treatment for malignant dysphagia.

Of 86 patients with inoperable malignant dysphagia, 68 (79 per cent) underwent successful palliation by endoscopic laser therapy, of whom 24 remained well palliated until the time of death. In 18 patients laser treatment was unsuccessful and nine of these underwent intubation, eight successfully. After successful laser therapy, dysphagia recurred in 44 patients a mean of 7.8 weeks later. Of these, 31 received palliation until death by dilatation with or without laser therapy, and 13 required intubation. The overall laser-related complication rate was 12 per cent with a mortality rate of 4 per cent. The intubation-related mortality rate was 9 per cent.

Adenocarcinoma

The function of large and small nerve fibers in renal failure.

Previous clinical and neurophysiological studies of uremic neuropathy have focused almost exclusively on the function of large sensory and motor axons. The sensations of heat and cold depend on the function of unmyelinated afferents and small myelinated afferents, respectively, and these sensations can be quantified using a standardized psychophysical technique. Thermal thresholds were measured in 20 patients with end-stage renal failure to determine the extent of small afferent fiber involvement and to compare this with the clinical and electrophysiological evidence of large fiber involvement. Whereas abnormalities of standard nerve conduction studies were found in 16 patients, abnormal thermal thresholds were found in only 6 patients. In the nerve conduction studies, the amplitudes of nerve potentials were reduced more than their conduction velocities, consistent with an axonopathy. This study found little evidence of significant dysfunction of small afferent fibers in end-stage renal failure and, when such changes occurred, they did not correlate with the clinical evidence of polyneuropathy. The functional sparing of axons of small diameter is consistent with the relative sparing of these axons in pathological studies.

Electromyography

Kinaesthetic signals and muscle contraction.

Signals generated both peripherally and centrally contribute to the group of sensations termed kinaesthesia. Many experiments report sensations of position and movement under passive relaxed conditions without muscle contraction. However, kinaesthetic acuity is probably of greater functional value when subjects are active rather than passive and, accordingly, movement detection is markedly improved by muscular contraction. One mechanism contributing to this enhancement is likely to involve muscle spindle volleys. When identical microstimulation techniques are applied to skin, joint and muscle spindle endings innervating the hand, some cutaneous afferents and some joint afferents elicit a sensation, but activation of certain other cutaneous afferents and muscle spindle afferents rarely does. Activity in more than one muscle spindle afferent may be required for kinaesthetic sensations, whereas some single cutaneous and joint afferents may have a more 'secure' central projection.

Animals

Assessment of corticospinal and somatosensory conduction simultaneously during scoliosis surgery.

The function of descending motor pathways and that of ascending sensory pathways in the spinal cord were monitored at the same time in 120 patients undergoing surgery for scoliosis. Transcranial electrical stimulation of the motor cortex was performed simultaneously with stimulation of the tibial nerves in the popliteal fossae, and the descending and ascending volleys were recorded from the spinal cord at two levels using epidural electrodes. Stable recordings of both volleys have been obtained in all neurologically normal patients and in many with pre-existing neurological deficits. The experimental conditions which resulted in reliable recordings were explored in select patients and include: a vertex-anode/lateral cathode montage for transcranial stimulation, epidural recording of evoked corticospinal and somatosensory volleys at two spinal levels, a high-pass filter of 500 Hz, and stable anaesthesia. The epidural recording allows full muscle relaxation and the use of volatile anaesthetics; recording at two levels allows a deterioration in function to be identified quickly and distinguished from an artifactual change.

Anesthetics

Anodal and cathodal stimulation of the upper-limb area of the human motor cortex.

In 18 neurologically normal subjects the corticofugal volleys evoked by anodal and cathodal electrical stimulation of the motor cortex were recorded using epidural electrodes at the high-thoracic and low-thoracic regions of the spinal cord during surgery for scoliosis. At and just above threshold, anodal and cathodal stimulation of the upper-limb area and motor cortex produced a D wave that propagated to the low-thoracic region. The stimulus intensity required to produce D waves was significantly lower with anodal stimulation. I waves were recorded at higher stimulus intensities than the D wave but not more readily with cathodal stimulation. There was no significant difference in the extent to which stimulus intensity had to be increased above D-wave threshold to produce I waves with the two stimulus polarities, and the number of I waves was the same when the stimulus was increased by the same amount above D-wave threshold. After withdrawal of isoflurane, I waves could not be recorded when the stimulus intensity was below D-wave threshold with either stimulus polarity. Anodal stimulation over the upper-limb area remained more effective than cathodal stimulation in producing both D and I waves. These results indicate that, at threshold, regardless of anaesthesia, anodal and cathodal stimuli access upper-limb corticospinal neurons directly at a similar site, the anodal stimuli being more effective. In addition, the results suggest that some corticospinal neurons in the upper-limb area of motor cortex have projections to lumbar segments.

Adolescent

Convergence of descending and various peripheral inputs onto common propriospinal-like neurones in man.

1. The patterns of excitation and convergence by peripheral afferents on propriospinal-like neurones projecting to forearm flexor carpi radialis (FCR) motoneurones in human subjects were determined at rest and during various voluntary contractions, using H reflex testing. 2. At rest, the FCR H reflex could be facilitated by mixed nerve (ulnar, musculocutaneous) and cutaneous (afferents from both sides of the hand) inputs. The characteristics of this facilitation (low threshold, long central latency, short duration) were compatible with those of the propriospinal-like system. Quantitatively this facilitation was rare and weak. 3. Voluntary contraction increased the extent of the propriospinal-like facilitation of the FCR H reflex. It is shown in the companion paper (Burke, Gracies, Meunier & Pierrot-Deseilligny, 1992) that this increase results not from a decrease in presynaptic inhibition of afferents to propriospinal-like neurones, but from increased excitation of these neurones. It is argued that at the onset of contraction this excitation is purely descending in origin, whereas the contraction-induced afferent discharge is probably the major factor during weak tonic contraction. 4. The distribution of the increased facilitation of the FCR H reflex depended on the muscles involved in the contraction: ulnar nerve-evoked facilitation was increased much more at the onset of voluntary wrist flexion than voluntary elbow flexion, and vice versa for the musculo-cutaneous-induced facilitation. This finding is consistent with the view that there are subsets of propriospinal-like neurones, specialized with regard to afferent input, and indicates that descending excitation is directed preferentially to the subset of neurones which receives excitatory feedback from the contracting muscle. 5. To investigate the convergence of different afferent inputs onto common neurones the spatial facilitation technique was used. When present the convergence had a threshold and time course compatible with those of the propriospinal-like system. Convergence was found between the different mixed nerves and between ulnar and superficial radial nerves. 6. The wide convergence found between different inputs onto common neurones and the finding that, during contraction of a given muscle, descending excitation reaches subsets of neurones projecting to motor nuclei of muscles operating at other joints suggest that the propriospinal-like system would be operative during complex multi-joint movements.

Adult

Changes in presynaptic inhibition of afferents to propriospinal-like neurones in man during voluntary contractions.

1. The possibility was investigated that the facilitation of the transmission in the propriospinal-like system during voluntary contraction, documented in the companion paper (Burke, Gracies, Mazevet, Meunier & Pierrot-Deseilligny, 1992), is due to a decrease in presynaptic inhibition of afferents projecting to propriospinal-like neurones. 2. The radial nerve was stimulated to evoke presynaptic inhibition of the monosynaptic Ia projections to forearm flexor motoneurones (Berardelli, Day, Marsden & Rothwell, 1987) and, hopefully, of the afferent input to propriospinal-like neurones projecting to these motoneurones. 3. The propriospinal-like excitation of forearm motoneurones evoked from mixed afferent inputs was depressed by radial nerve stimulation, and this depression was long-lasting (200 ms). Despite the convergence of mixed nerve and cutaneous afferents onto common propriospinal-like neurones, the radial stimulation did not depress the cutaneous-induced excitation. This differential effect and the time course of the depression suggest that it results from presynaptic inhibition of mixed nerve afferents (presumably large muscle afferents) projecting to propriospinal-like neurones. 4. With voluntary contractions, phasic or tonic, the radial-induced depression of the propriospinal-like excitation evoked by mixed nerve afferents was much greater than at rest, but the cutaneous-evoked excitation was unchanged. Thus, with voluntary contractions, there was no evidence of decreased gating of the afferent input to propriospinal-like neurones whether the input was of muscle or cutaneous origin and it is concluded that changes in presynaptic inhibition cannot account for the facilitation of the transmission in the propriospinal-like system during voluntary contraction. 5. By contrast, presynaptic inhibition of the monosynaptic Ia projections to motoneurones was consistently reduced at the onset of contraction, and to a much lesser extent during a weak tonic contraction.

Electric Stimulation

Physiological evidence for a slow K+ conductance in human cutaneous afferents.

1. The depression in axonal excitability that follows short trains of impulses (H1) may lead to spike frequency adaptation to a sustained stimulus, and has been attributed to a slow K+ conductance. The present experiments sought indirect evidence for slow K+ channels at the node of Ranvier of human cutaneous afferents based on the demonstration of post-tetanic changes in excitability typical of H1. 2. The excitability changes in low-threshold cutaneous afferents in the digital nerves of the index finger were explored using a submaximal test pulse conditioned by trains of supramaximal stimuli, containing up to 100 impulses. Changes in the amplitude of the compound sensory action potential set up by a constant test stimulus were used as a measure of the changes in excitability. These changes in amplitude were paralleled by inverse changes in latency. 3. When the conditioning stimulus was a single supramaximal pulse, excitability was enhanced at conditioning-test intervals of 4-40 ms, with a peak at 6-8 ms. When the conditioning stimulus consisted of a train of ten pulses delivered at 200 Hz, the recovery cycle was dominated by subnormality that was maximal at 20 ms and subsided gradually over 50 ms. 4. The post-train depression in excitability increased as the number of pulses in the conditioning train increased to ten but changed little with further increases in train duration. The degree of depression increased with the pulse frequency within the train. Cooling the hand from a skin temperature of 35 to 25 degrees C slowed the recovery processes but did not alter the magnitude of the post-train depression. 5. These characteristics are typical of the H1 phase of post-tetanic depression in axonal excitability. The extent of the depression in excitability suggests, first, that there may be a significant K+ conductance at the nodes of human cutaneous afferents and, secondly, that H1 may play a significant role in limiting repetitive discharge in normal and pathological afferents.

Axons

Coherence between the sympathetic drives to relaxed and contracting muscles of different limbs of human subjects.

1. This study was undertaken to quantify the simultaneous sympathetic drives to muscles in the two legs of human subjects, and to elucidate the extent to which a common drive determines sympathetic outflow to different limbs at rest, during apnoea and during voluntary contractions. 2. Sympathetic efferent activity was recorded simultaneously from fascicles of both peroneal nerves, innervating the pretibial flexor muscles. At rest the similarity was quantified for a sample of records by manual measurement of equivalent bursts in the two recordings, and for all records by cross-correlation and power spectral analysis of the two recordings. During contractions, only the latter method was used. 3. At rest the correlation coefficient for the relationship between the burst amplitudes for the two recordings was 0.72 (S.D. 0.1). For the same sequences, the computed coherence between the two recordings was 85.6% (S.D. 6.7%) at the cardiac period. There was a statistically significant linear relationship between these two measures of similarity, and this was stronger when data from sequences recorded during apnoea were included in the analysis. At rest the mean difference in coherence between consecutive sequences with no intervening manoeuvre (apnoea, contraction, change in recording site) was 4.2% (S.D. 4.3%). In only two of forty-nine such instances was the difference in coherence > 10%. 4. Apnoea at end-expiration increased the amplitude and frequency of sympathetic bursts and increased the similarity between the two recordings. The correlation coefficients increased from a mean of 0.72 at rest to 0.89 during apnoea. Coherence increased from a mean of 82.1% at rest to 91.9% during apnoea. 5. On the right side, graded voluntary contractions were performed at 5, 10, 20 or 30% maximal force using the muscle innervated by the fascicle from which the recording was made. The coherence between the recordings made from the right and left legs decreased by > 10% at each contraction level. Pooling the data for all contractions, there was a significant decrease in power at the cardiac frequency in the sympathetic recording from the contracting leg. Contraction of a synergist or antagonist at 10% maximum produced negligible changes in coherence. 6. It is concluded that, at rest, homologous muscles of the lower limbs are subject to a common drive and that, during apnoea, this common drive can dominate the sympathetic outflow to the virtual exclusion of regional drives. During voluntary activity, the importance of this common drive is lessened, presumably because of regionally specific changes involving the contracting muscle.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult

Corticospinal volleys evoked by electrical stimulation of human motor cortex after withdrawal of volatile anaesthetics.

1. In twenty-two neurologically normal patients undergoing surgery for scoliosis, corticospinal volleys to transcranial electrical stimulation of the motor cortex were recorded from the spinal cord using epidural electrodes. While anaesthesia was maintained by nitrous oxide and narcotics, volatile anaesthetics were withdrawn to determine whether such agents had a depressant effect on the evoked corticospinal volley. 2. Profound changes were documented in liminal D waves, there being an increase in amplitude averaging 392% following withdrawal of the volatile anaesthetic. There was a proportionately smaller increase (averaging 26%) in supraliminal D waves; these had a complex bifid or trifid shape indicating that some corticofugal axons were being activated deep to cortex. In general the effect on the D wave of withdrawing the anaesthetic agent was similar to that of increasing stimulus intensity. 3. Withdrawal of isoflurane dramatically increased the number of I waves and their mean amplitude. In the absence of isoflurane, I3 (mean latency 3.5 ms after the D wave) became the dominant I wave. The amplitude of I2 (mean latency 2.2 ms) became slightly smaller. The change in I waves could not be likened to an increase in stimulus intensity, because I waves invariably increase in, or remain of the same, amplitude as stimulus intensity is increased. 4. These findings indicate that changes in motor cortex excitability can result in major changes in the corticospinal volley produced by transcranial electrical stimulation, affecting both the D wave and I waves. They caution against identifying a cortical action solely on the basis of a change in the responses to magnetic stimulation of motor cortex but no such change to electrical stimulation.

Adolescent

Postural proprioceptive reflexes in standing human subjects: bandwidth of response and transmission characteristics.

1. This study investigated the reflex control of postural sway during human bipedal stance. The experiments were designed to: (i) find evidence for the operation of 'stretch reflex' pathways during quiet stance, (ii) determine the bandwidth of the reflex response, (iii) describe the reflex transmission characteristics in standing subjects, and (iv) assess the ability of subjects to make a task-dependent change in the reflex. 2. A continuous random perturbation that did not threaten stability was applied at waist level to nine standing subjects. The effects of the perturbation on ankle torque, ankle movement and soleus electromyographic activity (EMG) were identified by cross-correlation. The bandwidth of the reflex response and the transmission characteristics of reflexes that respond to ankle movement were identified by spectral analysis. Changes in these reflex responses were investigated when subjects attempted to stand as still as possible, had their eyes closed, or balanced a load equivalent to their own body in a situation in which neither visual nor vestibular reflexes would be activated. 3. When standing, a reflex response coherent with the perturbation was seen in soleus EMG at frequencies up to 5 Hz, with maximal coherence at 1.0-2.0 Hz. Reflex gain increased with frequency, and there was a frequency-dependent phase advance of soleus EMG on ankle movement reaching 135 deg at 3 Hz. When attempting to minimize sway, subjects produced a more coherent reflex response and significantly increased reflex gain. 4. The response and transmission characteristics of the lower limb proprioceptive reflex in freely standing subjects were similar to those in subjects balancing a load at the ankle, a situation in which vestibular and visual inputs could not contribute. 5. It is concluded that reflex feedback related to ankle movement contributes significantly to maintaining stance, and that much of the reflex response originates from lower limb mechanoreceptors stimulated by ankle rotation. Although reflex gain may be relatively low during quiet stance it can be increased when necessary to maintain stability.

Adult

Reflex responses in active muscles elicited by stimulation of low-threshold afferents from the human foot.

1. Reflex responses were elicited in muscles that act at the ankle by electrical stimulation of low-threshold afferents from the foot in human subjects who were reclining supine. During steady voluntary contractions, stimulus trains (5 pulses at 300 Hz) were delivered at two intensities to the sural nerve (1.2-4.0 times sensory threshold) or to the posterior tibial nerve (1.1-3.0 times motor threshold for the intrinsic muscles of the foot). Electromyographic (EMG) recordings were made from tibialis anterior (TA), peroneus longus (PL), soleus (SOL), medial gastrocnemius (MG), and lateral gastrocnemius (LG) muscles by the use of intramuscular wire electrodes. 2. As assessed by averages of rectified EMG, stimulation of the sural or posterior tibial nerves at nonpainful levels evoked a complex oscillation with onset latencies as early as 40 ms and lasting up to 200 ms in each muscle. The most common initial responses in TA were a decrease in EMG activity at an onset latency of 54 ms for sural stimuli, and an increase at an onset latency of 49 ms for posterior tibial stimuli. The response of PL to stimulation of the two nerves began with a strong facilitation of 44 ms (sural) and 49 ms (posterior tibial). With SOL, stimulation of both nerves produced early inhibition beginning at 45 and 50 ms, respectively. With both LG and MG, sural stimuli produced an early facilitation at 52-53 ms. However, posterior tibial stimuli produced different initial responses in these two muscles: facilitation in LG at 50 ms and inhibition in MG at 51 ms. 3. Perstimulus time histograms of the discharge of 61 single motor units revealed generally similar reflex responses as in multiunit EMG. However, different reflex components were not equally apparent in the responses of different single motor units: an individual motor unit could respond slightly differently with a change in stimulus intensity or background contraction level. The multiunit EMG record represents a global average that does not necessarily depict the precise pattern of all motor units contributing to the average. 4. When subjects stood erect without support and with eyes closed, reflex patterns were seen only in active muscles, and the patterns were similar to those in the reclining posture. 5. It is concluded that afferents from mechanoreceptors in the sole of the foot have multisynaptic reflex connections with the motoneuron pools innervating the muscles that act at the ankle. When the muscles are active in standing or walking, cutaneous feedback may play a role in modulating motoneuron output and thereby contribute to stabilization of stance and gait.

Adult

Long-lasting depression of central synaptic transmission following prolonged high-frequency stimulation of cutaneous afferents: a mechanism for post-vibratory hypaesthesia.

High-frequency vibration or electrical stimulation of cutaneous afferents may produce long-lasting hypaesthesia. Such stimulation alters the excitability of axons in the peripheral nerve but there is evidence that this does not completely explain the hypaesthesia. The present study was undertaken to determine whether a prolonged afferent barrage results in depression of synaptic transmission at a central site. Changes in central excitability to cutaneous inputs were examined in normal subjects by measuring the cerebral evoked potential at different stages after high-frequency conditioning stimulation of the digital nerves. Changes in peripheral excitability were eliminated by adjusting the stimulus intensity so that a constant afferent volley entered the central nervous system. Following the conditioning stimulation (4-5 T, 200 Hz, 10 min), the cortical potential evoked by constant submaximal test volleys was depressed by up to 50% for 25 min. The attenuation was less profound (10-20%) but more prolonged (greater than 45 min) when maximal test volleys were used, and occurred regardless of whether the high-frequency stimulation was applied to the test digit or to adjacent digits. It is concluded that prolonged activation of cutaneous afferents causes a depression in central excitability independent of and additional to peripheral changes, and it is suggested that this mechanism contributes to the associated perceptual disturbances. By analogy it is suggested that the hypaesthesia associated with prolonged vibration may be of central rather than peripheral origin.

Adult

Task-dependent changes in the responses to low-threshold cutaneous afferent volleys in the human lower limb.

1. In seven human subjects who were standing without support the sural nerves were stimulated electrically using trains of non-painful stimuli (five pulses at 300 Hz), designed to activate afferents from cutaneous mechanoreceptors. The reflex effects of the stimulus train on different muscles of the ipsilateral and contralateral legs were sought in post-stimulus averages of rectified EMG. Changes in the pattern of reflex influence were investigated when the subjects maintained different postures. 2. Clear reflex responses were seen in ipsilateral tibialis anterior, soleus, biceps femoris and vastus lateralis, but only when the muscles were actively contracting. In each muscle, inhibition was the dominant reflex response within the first 100 ms. In four of the seven subjects, reflex changes were detectable in the contralateral tibialis anterior and soleus, the peak-to-peak modulation within the first 200 ms being 25-50% of that for the homologous ipsilateral muscle. 3. When subjects attempted to stand on a tilted platform, an unstable platform or on one leg with the other flexed, different combinations of muscles were active, involving both flexors and extensors or predominantly flexors or predominantly extensors. In each posture the reflex effects were demonstrable only in the active muscles. 4. With ipsilateral tibialis anterior, there were task-dependent changes in the short-latency components of the EMG response, approximately 60 ms and 80 ms after the stimulus. When seated performing voluntary contractions these components were difficult to define, and when standing on a platform tilted toe-up they were small. When the ipsilateral leg was flexed or when standing on an unstable base, these early components were more prominent in each subject. With contralateral tibialis anterior, the dominant reflex pattern was inhibition when seated and contracting voluntarily, and facilitation during bipedal stance tilted toe-up. These changes in reflex pattern could not be explained by different levels of background contraction. 5. It is concluded that cutaneous mechanoreceptors of the foot have widespread reflex actions on muscles throughout both limbs, particularly the ipsilateral limb, and that the reflex pattern in different muscles and within a single muscle may change dependent on the task that the subject is undertaking. These task-dependent changes indicate plasticity in the expression of cutaneous reflex activity, affecting both short-latency spinal as well as long-latency pathways.

Adult

Decline in spindle support to alpha-motoneurones during sustained voluntary contractions.

1. To address whether the muscle spindle support to alpha-motoneurones is maintained during prolonged isometric voluntary contractions, the discharge of eighteen muscle spindle afferents, originating in the dorsiflexors of the ankle or toes, was recorded from the common peroneal nerve in eight subjects. Isometric contractions were generally sustained for 1 min, usually below 30% of the maximal voluntary dorsiflexion force. 2. Once the afferent had been identified, subjects were instructed to dorsiflex the foot slowly to recruit the spindle ending, to continue the ramp contraction until a predetermined target force was reached, and then to hold that force until requested to relax. 3. Five muscle spindle afferents maintained a constant discharge frequency during the hold phase of the isometric contraction. Following relaxation of the contraction two spindle afferents from tibialis anterior, exhibited a post-contraction discharge despite the absence of detectable electromyographic activity (EMG). 4. The discharge frequency of most of the spindle afferents (72%) declined progressively during the isometric contraction. The mean firing rates had declined to two-thirds of those at the onset of the contraction by 30 s, and to half after 1 min. The decline in spindle firing rate commenced during the ramp phase of the contraction and was statistically significant by 10 s, when force was held constant. The extent of the decline was greater for those units with the higher initial firing rates and for those units studied after many preceding contractions. 5. In the same contractions a progressive increase in EMG was required to maintain force and consequently the change in EMG was inversely related to the change in spindle discharge. While many mechanisms may contribute to the decline in spindle discharge during a sustained isometric contraction, it is argued that the result will be a progressive disfacilitation of alpha-motoneurones, which may contribute to the decline in motor unit firing rates during a sustained contraction.

Adult

High performance isoelectric focusing using capillary electrophoresis instrumentation.

High performance isoelectric focusing in capillaries provides rapid, high resolution separation of proteins based on their isoelectric points. Results can be obtained in a matter of minutes with little or no sample preparation. The technique requires the use of coated capillaries to reduce electroendosmosis so that stable, focused zones can be attained. Once focused, protein zones may be mobilized by the addition of salt to the catholyte or anolyte buffer. On-tube UV monitoring enables direct detection of sample components during mobilization with mass sensitivity equal to that of silver staining. The linear relationship between mobilization time and isoelectric point allows the technique to be used for estimation of protein pI. Demonstrated applications include separation of proteins in biological fluids with possible clinical applications, and characterization of biopharmaceutical proteins and monoclonal antibodies.

Capillary Action