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Biomedical subjects

D Burke

Publications and source records attributed to D Burke.

At least 19 recordsLinked to original sources
PubMed1999

Temperature dependence of excitability indices of human cutaneous afferents.

The temperature dependence of different indices of axonal excitability (threshold, latency, refractoriness, supernormality, strength-duration time constant, and rheobase) was studied for cutaneous afferents of 8 healthy human volunteers using threshold tracking. Cooling from approximately 32 - approximately 22 degrees C dramatically increased the threshold for a conditioned potential evoked during the relatively refractory period (average increase 573%) but had little effect on the threshold for unconditioned potentials (increased by 4% with 0.1-ms test stimuli), strength-duration time constant (increased by 18%), or rheobase (decreased by 12%). Cooling increased the latency of the unconditioned test potential by 41%, but this slowing was small compared with the effect of cooling on the latency slowing attributable to refractoriness. This measure of refractoriness was initially 0.17 ms at a conditioning-test interval of 2 ms, and increased with cooling to 1.30 ms at the same interval. With cooling, refractoriness was both greater at any one conditioning-test interval and longer in duration, extending into intervals normally associated with supernormality. It is concluded that, although cooling affects all excitability indices to some extent, the most prominent feature is the increase in refractoriness. By contrast, strength-duration time constant is influenced little by temperature.

Action Potentials↗
PubMed1998

The development of conduction block in single human axons following a focal nerve injury.

1. Using microneurography with a conventional monopolar electrode, the action potentials of ten myelinated axons in the peripheral nerves of human subjects were followed while they developed conduction block. 2. The action potentials had initially (n = 6) or developed (n = 4) a positive double-peaked morphology. The time interval between the two positive peaks represents the conduction time across the impaled internode. 3. When the interpeak interval was < 500 micros, conduction across the site of impalement was secure, even if the conduction time was markedly prolonged. When the interval was > 600 microseconds, intermittent conduction failure occurred. For all units the longest interpeak interval recorded just prior to complete conduction failure was, on average, 1.12 ms (range, 0.8-1.4 ms). 4. For five axons, there was evidence that natural activity triggered the conduction failure. 5. Impalement of the nerve fibre by the microelectrode impairs the ability of the axon to conduct impulses across the site of injury, but impulse transmission can be secure even when the conduction time across individual internodes is prolonged to 500 microseconds. These findings are therefore relevant to the conduction deficits that occur in focal injuries of human axons.

Action Potentials↗
PubMed1998

Biochemical characterization and subcellular localization of the mouse retinitis pigmentosa GTPase regulator (mRpgr).

The retinitis pigmentosa GTPase regulator (RPGR) gene encodes a protein homologous to the RCC1 guanine nucleotide exchange factor and is mutated in 20% of patients with X-linked retinitis pigmentosa. We have characterized the full-length and variant cDNAs corresponding to the mouse homolog of the RPGR gene (mRpgr). Comparison with the human cDNA revealed sequence identity primarily in the region of RCC1 homology repeats. As in humans, the mRpgr gene maps within 50 kilobases from the 5'-end of the Otc gene. The mRpgr transcripts are detected as early as E7 during embryonic development and are expressed widely in the adult mice. Variant mRpgr isoforms are generated by alternative splicing and by utilizing two in-frame initiation codons. The products of mRpgr cDNAs migrate aberrantly in SDS-polyacrylamide gels because of a charged domain. In transfected COS cells, the mRpgr protein is isoprenylated and is localized in the Golgi complex. This subcellular distribution is not observed after treatments with brefeldin A or mevastatin and when the conserved isoprenylation sequence (CTIL) at the carboxyl terminus is deleted or mutagenized. These studies suggest a role for the mRpgr protein in Golgi transport and form the basis for investigating the mechanism of photoreceptor degeneration in X-linked retinitis pigmentosa.

Alternative Splicing↗
PubMed1998

Activity-dependent hyperpolarization of human motor axons produced by natural activity.

1. The changes in excitability of motor axons produced by natural activity were measured in six healthy subjects using voluntary contractions lasting 15 s, 30 s and 1 min, by recording the changes in stimulus current required to produce a compound muscle action potential of approximately 60 % of maximum. 2. On cessation of the contractions there was a prominent increase in the current required to produce the target potential, accompanied by an increase in rheobase, a decrease in strength-duration time constant, and an increase in axonal supernormality. These changes indicate that the hypoexcitability was due to axonal hyperpolarization. 3. The activity-dependent hypoexcitability increased in depth and duration the longer the contraction. Following a 1 min contraction, it produced a 24 % increase in threshold, waning over 15 min. The hypoexcitability was greater than in cutaneous afferents tetanized to produce an equivalent rate-dependent stress. 4. It is concluded that natural activity results in substantial hyperpolarization of active axons and that, for similar discharge rates, the degree of hyperpolarization is greater in motor axons than cutaneous afferents. The greater effect of activity on the excitability of motor axons could be due to less inward rectification and less persistent Na+ conductance than in sensory axons. It is suggested that motor axons may therefore be more susceptible than cutaneous afferents to conduction block at sites of impaired safety margin for impulse conduction.

Adult↗
PubMed1998

Threshold tracking techniques in the study of human peripheral nerve.

Conventional electrophysiological tests of nerve function focus on the number of conducting fibers and their conduction velocity. These tests are sensitive to the integrity of the myelin sheath, but provide little information about the axonal membrane. Threshold tracking techniques, in contrast, test nerve excitability, which depends on the membrane properties of the axons at the site of stimulation. These methods are sensitive to membrane potential, and to changes in membrane potential caused by activation of ion channels and electrogenic ion pumps, including those under the myelin sheath. This review describes the range of threshold tracking techniques that have been developed for the study of human nerves in vivo: resting threshold is compared with the threshold altered by a change in environment (e.g., ischemia), by a preceding single impulse (e.g., refractoriness, superexcitability) or impulse train, or by a subthreshold current (e.g., threshold electrotonus). Few clinical studies have been reported so far, mainly in diabetic neuropathy and motor neuron disease. Threshold measurements seem well suited for studies of metabolic and toxic neuropathies but insensitive to demyelination. Until suitable equipment becomes more widely available, their full potential is unlikely to be realized.

Animals↗
PubMed1998

Ischemic resistance of cutaneous afferents and motor axons in patients with amyotrophic lateral sclerosis.

Compared with control subjects, patients with amyotrophic lateral sclerosis (ALS) have been reported to experience less or no paresthesias during and after release of ischemic compression of the upper arm for 10 min. This is reminiscent of the resistance to ischemia of diabetic patients, in whom sensory and motor axons undergo less ischemic depolarization and less postischemic hyperpolarization than in control subjects. The present study compared the changes in axonal excitability produced by ischemia for 10 min in 21 patients with ALS and 14 age-matched control subjects. Fewer patients reported intraischemic or postischemic paresthesias and the intensity of paresthesias was less, but this was significant only for postischemic paresthesias. There were quantitatively similar changes in refractoriness, supernormality, and strength-duration time constant during ischemic compression, but the increase in excitability of motor axons was less during the second half of ischemia in the patients. After release of ischemia the postischemic hyperpolarization was greater in the ALS patients, the opposite of what occurs in diabetes. These changes could reflect reduced intraneural K+ accumulation due to loss of motor axons or an alteration in nerve metabolism or membrane properties. Either way, the present study has failed to confirm previous reports of "ischemic resistance" in ALS, and indicates that the changes in axonal properties in ALS are not analogous to those in diabetes mellitus.

Adult↗
PubMed1998

Fibroblast growth factor receptors: lessons from the genes.

The fibroblast growth factor receptors (FGFRs) are a family of transmembrane tyrosine kinases involved in signalling via interactions with the family of fibroblast growth factors (FGFs). Genetic findings have provided a way of dissecting these interactions. Mutations in three members of the FGFR family have been found in patients with birth defects involving craniosynostosis (premature fusion of the cranial sutures) or skeletal abnormalities. Analyses of the spectrum of mutations found predict that many of them will result in ligand-independent activation of the receptors. Amino acids have also been identified that are likely to be important in determining the specificity of FGFR-FGF interactions.

Amino Acid Sequence↗
PubMed1998

Management of symptomatic locoregional recurrence during regional chemotherapy for colorectal liver metastases.

BACKGROUND: The incidence of symptomatic locoregional recurrence is doubled in patients receiving regional chemotherapy with hepatic arterial floxuridine infusion (HAI) compared with that in those with colorectal liver metastases treated by symptom control. This study assessed the management of symptomatic locoregional recurrence in HAI-treated patients with colorectal liver metastases. METHODS: A retrospective review of all patients with colorectal liver metastases treated by HAI in one hospital over a 10-year period was carried out and the management of those who developed symptomatic locoregional recurrence was studied. RESULTS: Twenty-three (14 per cent) of 166 HAI-treated patients with colorectal liver metastases developed symptoms of locoregional recurrence. Liver metastases were responding to HAI at the onset of symptoms in 19 (ten abdominal, nine pelvic recurrence) of the 23 patients. Resection of abdominal recurrence was possible in seven of the ten patients, with a median hospital stay of 14 days; there was one perioperative death. Resected patients survived a median of 15 months after resection of the recurrence, with five of seven remaining free of symptoms of locoregional recurrence. In contrast, six of nine HAI-responding patients with pelvic recurrence treated by external beam radiotherapy died from uncontrolled symptomatic pelvic disease. CONCLUSION: Resection of abdominal recurrence achieved worthwhile palliation in patients with HAI-controlled liver metastases, but palliation of pelvic recurrence by irradiation was unsatisfactory.

Abdominal Neoplasms↗
PubMed1998

Quantitative description of the voltage dependence of axonal excitability in human cutaneous afferents.

The voltage dependence of indices of axonal excitability were quantified for cutaneous afferents in eight normal subjects, using the threshold for a target compound sensory action potential as a measure of membrane potential. The membrane potential was altered using subthreshold depolarizing and hyperpolarizing currents of various sizes (-50% to +50% of threshold). Refractoriness and supernormality were determined as the threshold change required to produce the target potential when preceded by a supramaximal stimulus at appropriate conditioning-test intervals. The strength-duration time constant (tauSD) was calculated from the threshold currents using unconditioned test stimuli of 0.1 and 1 ms. There was a near-linear relationship between each of these indices and the reciprocal of threshold (a measure of 'excitability'). It is argued that the voltage dependencies of refractoriness and tauSD largely reflect the behaviour of transient and persistent Na+ channels, respectively, and that the present data therefore quantify aspects of Na+ channel behaviour in human nerves.

Axons↗
PubMed1998

Strength-duration properties of sensory and motor axons in amyotrophic lateral sclerosis.

In normal subjects, the strength-duration time constant is longer for cutaneous afferents than for motor axons, probably because the former express a greater non-inactivating (persistent) Na+ conductance that is active at threshold. Using a threshold-tracking system the strength-duration properties of cutaneous afferents and motor axons were recorded from 23 patients with amyotrophic lateral sclerosis, and compared with those of 32 healthy subjects. In control subjects and patients, the strength-duration time constant of sensory fibres declined with age, and there was no difference between the two groups when age was taken into account. The motor time constant did not change with age when expressed as a percentage of the time constant for sensory fibres in the same nerve, but was significantly longer for the patients than control subjects. In addition, motor rheobase was significantly lower for the patients, when expressed as a percentage of sensory rheobase. There was an inverse relationship between the time constant and rheobase for sensory and motor axons, and this was the same for the patients and the control subjects, suggesting that the variations in time constant within and between the groups were related to the expression of a common factor. Measurements of refractoriness and supernormality provided no evidence for a difference in resting membrane potential between the patients and control subjects. These findings are consistent with the interpretation that motor axons of the patients with amyotrophic lateral sclerosis have a greater persistent Na+ conductance than normal motor axons. This could contribute to the ectopic activity responsible for fasciculation.

Adult↗
PubMed1998

Surgical monitoring of motor pathways.

Intraoperative monitoring of corticospinal function is no longer an experimental technique, having been introduced into routine practice in a number of centers, each of which has now accumulated large series of some hundreds of cases. Different techniques have been developed by these centers; each has advantages and disadvantages, and it is clear that no one technique in particular is optimal for all surgical procedures. The corticospinal system can be activated by transcranial stimulation of the motor cortex or by direct stimulation of the spinal cord with electrical or magnetic stimuli delivered singly or as double or multiple pulses. The evoked activity may be recorded directly from the spinal cord using epidural electrode, or as a postsynaptic volley in motor axons ("neurogenic motor evoked potentials," MEP), or as a compound muscle action potential (CMAP) from innervated muscles. For scoliosis surgery, we use transcranial electrical stimulation, recording the evoked volley from the spinal cord using epidural electrodes at two spinal levels. By simultaneously stimulating the tibial nerves in the popliteal fossae, descending corticospinal volleys and ascending somatosensory volleys can be recorded in the same sweep. Accordingly, this technique allows monitoring of two different modalities of function at two separate levels of the nervous system, a goal that is most desirable because it helps identify the earliest evidence of dysfunction and at the same time minimizes false-positive reports to the surgeon. Our technique has the advantage of being relatively immune to the depressant effects of anesthesia, and full muscle relaxation is possible--even desirable. More peripheral recordings of neurogenic MEP or CMAP, are sensitive to the choice of anesthetic, and the latter requires incomplete curarization. However, these techniques may be appropriate when the pathology is in the low spinal cord or nerve roots.

Evoked Potentials, Motor↗
PubMed1998

Early intervention in schizophrenia in the elderly.

OBJECTIVE: The aim of this paper is to briefly review the literature on early intervention in schizophrenia in the elderly, and to present six cases of schizophrenia in the elderly which highlight the need for assertive management of the type encouraged widely for early onset illness in younger patients. METHOD: Six case histories are presented. RESULTS: All six patients were diagnosed with DSM-IV schizophrenia, all were single and all were socially isolated. They required involuntary admission, treatment with depot antipsychotics, extensive psychosocial intervention and community treatment orders. The use of these treatment strategies led to a positive outcome in each case. CONCLUSION: The authors argue that assertive treatment of elderly patients with schizophrenia should be pursued with the enthusiasm often reserved for younger, early onset patients, and that therapeutic optimism is required and warranted.

Age Factors↗
PubMed1997

Mental rehearsal of motor tasks recruits alpha-motoneurones but fails to recruit human fusimotor neurones selectively.

1. As mental rehearsal of movements activates multiple cortical areas associated with movement, we assessed whether this increases fusimotor drive and whether enhanced muscle spindle activity could contribute to the improvement in skill that accompanies mental rehearsal. 2. Microneurographic recordings were made from six muscle spindle afferents innervating extensor muscles in the forearm or tibialis anterior, which were selected because their discharge increased during very weak contractions. Activity was monitored while subjects imagined performing a range of activities including simple and complex movements involving the relevant muscles. 3. No activation of muscle spindle afferents occurred during imagined motor tasks without EMG. When the relevant muscles contracted during mental rehearsal, spindle discharge increased, much as in weak contractions. 4. Mental rehearsal increased background EMG in the involved muscles and also increased H reflex amplitude independently of EMG changes. 5. Although there was no evidence for selective fusimotor activation during imagined movement, skeletomotor activity and reflex excitability increased. Similar changes occur with preparation for movement following a cue. It is likely that mental rehearsal usually involves unintentional performance of the planned motor task.

Adult↗
PubMed1997

Discharge of human muscle spindle afferents innervating ankle dorsiflexors during target isometric contractions.

1. There are discrepancies in the literature about the reproducibility of forces at which human muscle spindle afferents accelerate their discharge during isometric voluntary contractions. The aim of this study was to determine for single muscle spindle afferents both the reproducibility of the 'acceleration threshold' and the factors contributing to variability of 'acceleration threshold'. 2. Microneurographic recordings were made from muscle spindle afferents innervating tibialis anterior while subjects performed isometric ankle dorsiflexions. Subjects matched the force of their contractions with a visually displayed 'ramp-and-hold' template. Template parameters were determined by the force of maximal isometric ankle dorsiflexion (MVC), and expressed as per cent MVC. The required 'ramp' rate and 'hold' force was adjusted between trials (range, 0.5-5% MVCs-1 and 0.5-20% MVC, respectively). The duration of the hold phase was 4 s and, following each contraction, stretch was applied transversely to the tendon to minimize the influence of any 'after-effects' on spindle afferent responses in subsequent contractions. 3. For each contraction, the force at which the rate of muscle spindle discharge increased was defined as the 'acceleration threshold'. Of twenty-six muscle spindle afferents innervating tibialis anterior, all but two increased their discharge in the test contractions. In 90% of contractions, acceleration thresholds were less than 3.2% MVC (range, 0.01-11.9% MVC). 4. Individual muscle spindle afferents increased their discharge at similar but not identical forces in repeated contractions. There was a positive correlation between the rate of contraction and the acceleration threshold (P < 0.001), but the strength of the target contraction had no effect on the threshold, and there was no trend for thresholds to change over time. 5. The results suggest, first, that most muscle spindle endings in the human pretibial muscles receive a significant increase in fusimotor drive during relatively weak isometric efforts and secondly, that when fusimotor after-effects are controlled, much of the residual variability in 'acceleration threshold' for any one spindle in repeated contractions is due to extrafusal factors, particularly variability in contraction rate.

Acceleration↗