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Biomedical subjects

D Burke

Publications and source records attributed to D Burke.

At least 145 records · Page 8Linked to original sources

Effects of femoral nerve stimulation on the electromyogram and reflex excitability of tibialis anterior and soleus.

The present study was undertaken to determine whether femoral nerve stimulation would produce heteronymous reflex responses in tibialis anterior (TA) and soleus, demonstrable by averaging the electromyogram (EMG) produced by a voluntary contraction, and whether the responsible changes in excitability were sufficient to affect the H reflexes of TA and soleus. In both muscles, femoral stimuli produced short-latency, presumably monosynaptic excitation, better defined in poststimulus averages of unrectified EMG, followed by long-lasting inhibition, better defined in averaged rectified traces. The H reflexes underwent changes at appropriate latencies. The thresholds for excitation and inhibition were, respectively, below and above threshold for the quadriceps M wave. The heteronymous responses were largely independent of stimulus rate and, within limits, scaled with the level of background contraction. The ability to define these heteronymous connections using relatively simple methodology extends their utility. Such tests may prove useful in probing pathophysiological mechanisms in individual patients.

Adult↗

Morphology of action potentials recorded from human nerves using microneurography.

This study investigated the morphology of action potentials and the frequency of occurrence of the various waveforms encountered when using microneurography to record single-unit muscle afferent activity in humans. With 75% of the afferents recorded in this study (55 of 73 afferents), action potentials had a double-peaked morphology. For action potentials with an initial, positive double-peaked morphology, the relevant afferent conducts impulses past the microelectrode, with the second peak representing current fluctuations at the node of Ranvier proximal to the electrode. Accordingly, in the majority of recordings, the afferent is capable of conducting impulses to the spinal cord. The mean interpeak interval for these double-peaked units was 168 microseconds (range 90-310 microseconds). This represents marked prolongation of conduction time across the impaled internode. When the interpeak interval was relatively short (90-120 microseconds), the double-peaked morphology could be recognized only if the low-pass filter was high (> or = 10 kHz). The probability of recording a double-peaked unit was the same whether the recording was acquired early or late in a 3-h experiment. Conduction block developed in 6 of 73 single units during the recordings. These findings indicate that the majority of isolated single afferents and, indeed, the majority of afferents within the relevant fascicle are capable of transmitting impulses across the recording site, even though conduction across the impaled internode is slow. Conduction block due to direct injury or pressure is relatively uncommon.

Action Potentials↗

Further evidence for monocular determinants of perceived plaid direction.

This report adds to existing evidence that a monocular, feature-sensitive motion mechanism is involved in two-dimensional (2-D) motion processing, and also accounts for an earlier, unexplained result [Alais et al.(1994) Vision Research, 34, 1823-1834]. The central finding is that the perceived direction of a monocularly viewed type II plaid changes over a period of continuous exposure such that post-adaptation direction judgements exhibit more of the component-direction bias known to occur with these stimuli than pre-adaptation judgements. These adaptation effects are confined to the adapted eye: when the adapting stimulus is presented to one eye, pre- and post-adaptation direction judgements made with the other, non-adapted eye are identical. These results strongly suggest the involvement of a monocular motion mechanism in two-dimensional motion processing, in addition to the more commonly presumed binocular mechanisms.

Adaptation, Ocular↗

Differences in stiffness of the interface between a cementless porous implant and cancellous bone in vivo in dogs due to varying amounts of implant motion.

To determine the mechanical properties of the interface between the tissue ingrowth into porous coatings and the implant, porous-coated cylindrical implants were inserted into the distal femur in 20 mature dogs and oscillated in vivo 8 hours per day for 6 weeks at fixed amounts of micromotion (0, 20, 40 and 150 microns). Applied torques and resulting displacements were recorded. The torsional resistance per unit angular displacement (TR/AD), reflecting the stiffness of the bone-porous coating interface, was 0.88 +/- 0.25 N-M/deg immediately after implantation in the 20-micron displacement group. It increased with time after surgery, reaching a maximum of 1.25 +/- 0.60 N-M/deg at 6 weeks. The TR/AD was lower initially (0.77 +/- 0.43 N-M/deg) in the 40-micron group and gradually decreased with time after surgery, reaching a maximum of 0.54 +/- 0.13 N-M/deg at 6 weeks. The TR/AD was even lower (0.24 +/- 0.10 N-M/deg) in the 150-micron group initially and remained the same (0.16 +/- 0.09 N-M/deg) with time after surgery. Histologic evaluation showed bone ingrowth in continuity with the surrounding bone in the 20-micron group consistent with the high stiffness values at sacrifice. In contrast, a mixture of fibrocallus and bone were found at the bone-porous coating interface in the 40-micron group, consistent with the intermediate stiffness values. In contrast, despite the fact that bone was found in the depth of the porous coating in the dogs in the 150-micron group, the low stiffness values were a reflection of fibrous tissue formation at the interface in that group, because of the large motion disrupting bony ingrowth at the bone-porous coating interface. By monitoring the torsional resistance per unit of angular displacement dynamically in vivo, it was possible to evaluate the mechanical properties of the bone-porous coating interface as tissue ingrowth proceeded. Twenty microns of oscillating displacement was compatible with stable bone ingrowth with high interface stiffness, whereas 40 and 150 microns of motion was not.

Animals↗

Activity-dependent changes in impulse conduction in a focal nerve lesion.

The present study was undertaken to determine whether, in patients with a focal nerve lesion, the axonal hyperpolarization produced by conduction of brief trains of impulses would result in conduction block in cutaneous afferents, thus indicating a site of impaired safety margin for impulse transmission. In 25 patients with focal conduction slowing across the carpal tunnel segment of the median nerve, a conditioning train of 10 supramaximal stimuli at 200 Hz resulted in a reduction in amplitude and an increase in latency of the test volley set up by a supramaximal stimulus. These changes exceeded those seen in control subjects, but followed a similar time course, with full recovery within 150 ms. There was a significant correlation between these changes and the severity of the compression neuropathy as indicated by the degree of focal conduction slowing in routine nerve conduction studies. Control data suggested that the measured changes in amplitude could be explained by temporal dispersion of the compound sensory volley. This view was supported by measurements of the changes in amplitude (and latency) in normal subjects during acute compression before conduction block had developed. In addition, there were similar linear relationships between the activity-dependent amplitude reduction and the corresponding change in latency for both the patients and the control subjects, indicating that there was no need to invoke factors additional to those operating in the control subjects to explain the greater amplitude depression in the patients. It is concluded that, although the depression in amplitude was greater in patients than in healthy subjects, the magnitude of this change can be explained by temporal dispersion of the abnormal compound sensory action potential associated with greater conduction slowing. Activity-dependent conduction block may play little role in the pathophysiology of carpal tunnel syndrome.

Action Potentials↗

Strength-duration properties of human peripheral nerve.

The strength-duration time constant (tau SD) is a property of nodal membrane and, while it depends on a number of factors, its measurement may shed light on axonal properties when taken in conjunction with measurements of axonal excitability. For example, tau SD increases with demyelination as the exposed membrane is enlarged by inclusion of paranodal and internodal membrane, it decreases with hyperpolarization and it increases with depolarization. The present study was undertaken in 20 normal volunteers to compare strength-duration curves for compound sensory and muscle action potentials, to determine the most appropriate curve fitting equation for the data, and to examine the reproducibility of the calculated time constant on different days, for potentials of different amplitude and at different sites along the nerve. Using a computerized threshold-tracking system, stimulus intensity was adjusted to produce an antidromic compound sensory action potential (CSAP) or an orthodromic muscle action potential of 30% of maximum. Stimulus duration was increased every minute in 20 microseconds steps from 20 microseconds to 1 ms. The time constant for compound sensory potentials (665 +/- 182 microsecond) was longer than that for compound EMG potentials (459 +/- 126 microseconds). Weiss's formula, which relates threshold charge to stimulus duration, provided an accurate fit for the experimental data, and the study validated that, using it, relatively few experimental measurements were required to calculate the time constant. In repeated studies on the same subject, time constants usually differed by < 400 microseconds for sensory axons and < 250 microseconds for motor axons. They were identical at different sites along the nerve and did not alter with the size of the compound action potential. These characteristics suggest that the determinations of strength-duration time constant could be suitable for clinical usage.

Adult↗

Differences in the recovery of excitability in sensory and motor axons of human median nerve.

Following conduction of an action potential there is a stereotyped sequence of changes in excitability as axons are initially refractory, then superexcitable and finally subexcitable. These activity-dependent oscillations in excitability subside over 100 ms and together constitute the recovery cycle. The present study was undertaken first to document the recovery cycle of sensory and motor axons of different threshold and, secondly, to compare the changes in sensory axons with those in motor axons. A computerized threshold-tracking system was used to measure recovery cycles in six healthy subjects; stimuli were applied to the median nerve at the wrist. Changes in the threshold required to produce an antidromic compound sensory action potential (CSAP) and an orthodromic compound muscle action potential (CMAP) of fixed amplitude (30%, 50% and 70% of maximal) were recorded following a single supramaximal conditioning stimulus. Normalized recovery cycles were identical for axons of different threshold, whether sensory or motor, and were reproducible on repeat testing. However, there were significant differences between the changes in sensory and motor axons, with greater supernormality and greater late subnormality in motor axons. The greater changes in motor axons could not be explained by differences in the strength-duration properties of sensory and motor axons. There are biophysical differences in the properties of sensory and motor axons and these differences may underlie the differential susceptibility of sensory and motor axons in peripheral nerve disorders.

Adult↗

Changes in excitability and impulse transmission following prolonged repetitive activity in normal subjects and patients with a focal nerve lesion.

The present study was undertaken to document the excitability changes produced by prolonged high-frequency trains of impulses and to determine whether these changes in excitability would impair neural transmission in cutaneous afferents of patients with focal slowing of conduction across the carpal tunnel. A submaximal test stimulus was used to measure the changes in axonal excitability following trains of supramaximal stimuli delivered at 200 Hz for 30 s, 1 min or 2 min. These trains produced a prolonged depression in excitability in normal axons with gradual recovery to control levels over 20-30 min, presumably due to hyperpolarization associated with activation of the electrogenic Na+/K+ pump. The decrease in excitability was demonstrable at nerve segments remote from the site of tetanic stimulation. Based on these findings, the effects on neural transmission were then assessed in normal subjects and patients using a supramaximal test stimulus following a 1-min tetanic train. In normal subjects there was a small activity-dependent decrease in amplitude of the compound sensory action potential (CSAP) associated with a prolongation in its latency. In patients with focal slowing of conduction across the carpal tunnel there was a more marked post-tetanic prolongation in latency, but the reduction in amplitude of the maximal CSAP was no greater than in the control subjects. It is concluded that activity-dependent conduction block is not a major cause of symptoms in carpal tunnel syndrome. It is suggested that the conduction slowing seen in patients with mild-moderate carpal tunnel syndrome could result from mechanisms other than demyelination.

Action Potentials↗

Colorectal liver metastases.

Each year in the UK, between 12-14,000 people develop liver metastases from colorectal cancer. These metastases will contribute to the death of the patient in about 80% of cases. Treatments aimed at these tumours are best administered when the tumour is small. Current investigative methods allow tumours as small as 0.5 mm to be detected, and should be offered to all colorectal cancer patients at risk of developing liver metastases. Surgery remains the only curative treatment for these tumours, but, unfortunately, only 20% of those who have tumour excision will survive five years. In those patients unsuitable for surgery, chemotherapy with fluoropyrimidines produces the best tumour response. This may be administered systemically or regionally, via a catheter placed within the hepatic artery. The latter approach reduces systemic toxicity, but may produce hepatotoxicity. The results of other forms of systemic chemotherapy currently undergoing clinical trials are awaited. The vast majority of patients will benefit from suitable palliative treatment delivered either locally or systemically. With the wide range of treatments now available for liver metastases, these patients are best assessed in a unit with a special interest in the problem.

Antineoplastic Agents↗

Loop gain of reflexes controlling human standing measured with the use of postural and vestibular disturbances.

1. In this study we measured the loop gain of postural reflexes in standing human subjects. Reflex activity is conventionally described in terms of the muscle activation arising from a perturbation, but in this study the ability of the evoked muscle activity to correct the perturbation was also measured, and the behavior of the entire feedback loop is described. 2. A weak continuous random perturbation was applied at waist level to standing subjects. The effects of the perturbation on body sway and soleus electromyogram (EMG) were identified by cross-correlation, and spectral analysis was used to estimate the open-loop reflex transmission characteristics (i.e., sway to EMG). Under the same conditions, activity in the leg muscles was evoked by galvanic vestibular stimulation with the use of a continuous randomly varying current. The effects on soleus EMG and the subsequent body sway were identified by cross-correlation. This allowed calculation of the open-loop muscle and load behavior (i.e., EMG to sway). From these open-loop reflex and muscle and load transfer functions, the loop gain and phase were calculated. 3. In addition to the gain of the feedback loop, the study describes the transmission characteristics of reflex responses in the leg muscles associated with body sway and the effects of excluding visual and proprioceptive contributions to the response; the transfer function of human soleus with a stimulus that preserves the normal recruitment of motoneurons, including the effects of different load conditions on the muscle; and the transmission characteristics of vestibular pathways that evoke responses in the leg muscles during standing in situations that might modify the reflexes. 4. When standing, the loop gain of reflex feedback is approximately unity and is unchanged by eye closure and stability of support. Reflex transmission introduced a marked phase advance, and this served to offset most of the phase lag introduced by muscle and load. The residual phase lag could explain the frequency of tremor observed during standing (6-8 Hz). 5. The gain of the feedback loop (approximately 1) is higher than suggested by both previous estimates and theoretical considerations, but is still insufficient to explain the stability of normal human standing. This implies that, although sensory information is used to control posture, it does not do so exclusively through a negative feedback control process. The experimental findings are consistent with a reflex response based on a feed-forward process, and this would result in prediction of the response necessary to counteract a postural disturbance.

Adult↗

Relation between tumor size, quality of life, and survival in patients with colorectal liver metastases.

PURPOSE AND METHODS: This study assessed the relationship between survival, tumor size, and quality of life (QoL; Rotterdam Symptom Checklist [RSC], Hospital Anxiety and Depression Scale [HAD], and Sickness Impact Profile [SIP]) in 50 patients with colorectal liver metastases (CLM). RESULTS: Physical symptom score (RSC) was a stronger survival predictor than tumor size measured on computed tomographic (CT) scan. The best model for predicting survival included QoL questions about diarrhea, eating, restlessness, and ability to work and sleep. The only clinically measured variable included in this best survival prediction model was serum alkaline phosphatase level. This is the first study to show that QoL indices predict survival in CLM. The findings suggest that differences in tumor products and not just in tumor size could influence patient fitness and survival in CLM. Such differences are more accurately estimated by QoL assessment than measurement of tumor size. CONCLUSION: QoL provides a better survival estimate than measurement of tumor size and could be used as a surrogate end point for survival in treatment trials.

Aged↗

Fluoxetine and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH)

OBJECTIVE: To report three new cases of the fluoxetine-induced syndrome of inappropriate secretion of antidiuretic hormone (SIADH). CLINICAL PICTURE: All three cases occurred in elderly psychiatric inpatients treated for depression with standard doses of fluoxetine within one month of starting the medication. All three patients were clinically symptomatic of SIADH. TREATMENT: In all three patients the medication was ceased and fluid restriction commenced. One patient required intravenous saline. OUTCOME: All three patients recovered fully within three weeks. None were rechallenged. CONCLUSIONS: The symptoms of hyponatraemia due to fluoxetine-induced SIADH may be difficult to distinguish from the symptoms of depression, unless appropriate laboratory investigations are made.

Aged↗