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D Burke

Publications and source records attributed to D Burke.

At least 73 records · Page 4Linked to original sources

Strength-duration properties and their voltage dependence as measures of a threshold conductance at the node of Ranvier of single motor axons.

In a number of clinical studies, measurement of axonal strength-duration properties has been used to provide indirect insight into conductances at the node of Ranvier, particularly persistent Na(+) conductance. However, the specificity of any changes is limited because other factors can affect strength-duration behavior. The present study was undertaken to define the relationship between different strength-duration measures at rest and at different membrane potentials, and also to determine the limits within which strength-duration behavior can be used as a measure of nodal conductances. The strength-duration time constant (tau(SD)) and rheobase of 20 single motor units in the flexor carpi ulnaris were calculated from thresholds defined using threshold tracking. "True" rheobase and rheobasic latencies were measured using test stimuli of 100-ms duration. For ten units, the technique of latent addition was used to measure threshold changes directly attributable to nodal conductances, and for six units these were compared with strength-duration properties at different membrane potentials. The data indicate that measurements of tau(SD) and rheobase can provide sensitive indicators of conductances present at the node of Ranvier when membrane potential changes. There is a reciprocal relationship between tau(SD) and rheobase for single motor units at different membrane potentials, and this relationship may allow changes in tau(SD) due to depolarization and demyelination to be differentiated.

Action Potentials↗

Characterization of bovine collagens using capillary electrophoresis.

A capillary electrophoresis method was developed and characterized for analyzing the spectrum of collagen subspecies in collagen preparations. The Bio-Rad CE-SDS protein kit was used for the dynamic sieving separation of collagen subspecies in this CE method (DSCE). The optimized method utilized a 36 cm (or 24 cm) x 50 microm uncoated capillary, electrophoretic injection at 10 kV for 10 s, a run voltage of 15 kV, a capillary temperature of 20 degrees C, and UV detection at 220 nm. A preliminary validation of the method was performed. The assay had good repeatability (RSDs for peaks were 15%), and responses were linear for assay solutions with collagen concentrations from 0.125 to 1.25 mg/ml. The DSCE electropherogram of bovine skin collagen provided a profile of subspecies similar in number and relative abundance to that generated by scanning of Coomassie-stained SDS-PAGE gels.

Animals↗

Reproducibility of indices of axonal excitability in human subjects.

OBJECTIVES: Different indices of axonal excitability are now being measured in human subjects, both normal volunteers undergoing some test manoeuvre and patients with a variety of peripheral nerve disorders. The reproducibility of these indices has not previously been established, and was determined for cutaneous afferents in the median nerve of 12 healthy subjects, using threshold tracking techniques. METHODS: Refractoriness and supernormality were determined as the change in stimulus current required to produce a predetermined target potential when conditioned by a supramaximal stimulus at appropriate conditioning-test intervals. Strength-duration time constant was calculated from the threshold currents using unconditioned test stimuli of 0.1 ms and 1.0 ms. The effects of changes in membrane potential on these indices was assessed by applying subthreshold DC currents (from 50% depolarizing to 50% hyperpolarizing), using the reciprocal of threshold (i.e., 'excitability') as an indicator of membrane potential. The intraindividual reproducibility was determined by repeating the study on each subject up to 10 times. RESULTS: Refractoriness and supernormality were variable between subjects (mean +/- SD of 31.5 +/- 9.5% and 13.2 +/- 3.8%, respectively) and within subjects (coefficient of variation 0.2104 and 0.21849, respectively). TauSD showed even greater interindividual variability (499.2 +/- 115 micros) and intraindividual variability (coefficient of variation 0.2339). The slopes of relationships between each of the indices and axonal 'excitability' suggest that refractoriness is extremely sensitive to changes in excitability (0.9767 +/- 0.1907), tauSD less so (0.3766 +/- 0.1322), supernormality least (0.2223 +/- 0.1268). CONCLUSIONS: Under controlled conditions, refractoriness is the most sensitive and least variable of the indices of axonal excitability. However, small decreases in temperature greatly increase refractoriness but have little effect on tauSD. Given that 3 indices reflect different biophysical mechanisms, nodal and internodal, greater insight into the functional state of peripheral nerve axons will come when there are coherent changes in all 3 indices.

Adult↗

Correlation between tumour blood flow and fluorouracil distribution in a hypovascular liver metastasis model.

The poor response of colorectal liver metastases to fluorinated pyrimidine chemotherapy may be due to poor drug penetration into the tumour. Chemotherapy delivered by the blood to well perfused areas of tumour must reach less well perfused areas by diffusion. This study examined the relationship between intratumoural blood flow and drug uptake in a hypovascular liver metastasis animal model. We used a double isotope technique to examine the microdistribution of the blood flow tracer [125I]-iodoantipyrine (IAP) and fluorinated pyrimidine 5-[6-3H]-fluorouracil (5-FU) within intrahepatic, hypovascular HSN tumours. There was a significant fall (P < 10(-6)) in both IAP and 5-FU uptake between the liver/tumour edge and tumour centre which resulted in a significant covariation (P < 10(-5)) in tracer uptake with distance. The finding of a close covariation between blood flow and drug uptake in liver metastases suggested that 5-FU diffusion did not compensate for low 5-FU delivery in areas of poor tumour blood flow. The lower 5-FU levels in low compared with high areas of tumour blood flow could reduce the cytotoxic effect and increase the potential for development of drug resistance.

Animals↗

Integration of the genetic and physical maps of the chicken macrochromosomes.

A large amount of genetic mapping information has been obtained in the chicken from the East Lansing, Compton and Wageningen reference populations. Physical mapping information has however, been more limited. We have mapped 14 new clones, both genetically and physically, and all 14 have been assigned to macrochromosomes. The orientation of linkage groups E01C01C11W01 (Chr 1), E06C02W02 (Chr 2), E02C03W03 (Chr 3), E05C04W04 (Chr 4), E07E34C05W05 (Chr 5), E11C10W06 (Chr 6), E45C07W07 (Chr 7) and E43C12W11 (Chr 8) has been established. Here we present integrated maps of the eight macrochromosomes and the Z chromosome of the chicken and correlate genetic with physical distances for chromosomes 1-3 and the Z sex chromosome.

Animals↗

Short-term effects of dynamic lycra splints on upper limb in hemiplegic patients.

OBJECTIVE: To assess acceptability, effects on swelling, resting posture, spasticity, and active (AROM) and passive range of motion (PROM) of individually tailored upper limb Lycra garments, designed as dynamic splints to exert directional pull on certain limb segments, when worn for 3 hours by hemiplegic patients. DESIGN: Crossover trial. SETTING: Outpatient and inpatient rehabilitation center. PATIENTS: Convenience sample of 16 patients with hemiparesis and upper limb spasticity caused by a stroke more than 3 weeks before the study. INTERVENTIONS: Assessments performed at the start and end of a 3-hour period during a standard rehabilitation day when the patients were and were not wearing the garment. MAIN OUTCOME MEASURES: (1) Comfort assessed by questionnaire; (2) circumference of each limb segment; (3) resting posture at elbow and wrist; (4) spasticity at shoulder, elbow, and wrist using the Tardieu scale; and (5) AROM and PROM at shoulder, elbow, and wrist measured using a goniometer; (6) elbow proprioception using McCloskey's method; (7) visual neglect syndrome using the line bisection test. Differences between changes occurring with and without the garment were compared using Wilcoxon's signed rank test for ordinal variables (spasticity grading) and Student's t test for continuous variables (all other data). RESULTS: During 3 hours, garments worn on the arm by patients with hemiplegia (1) were comfortable, (2) improved wrist posture and reduced wrist and finger flexor spasticity, (3) reduced swelling in patients with swollen limbs (digit circumference decreased by 4%; p<.01), (4) improved PROM at shoulder (mean increase in range, 4.1 degrees +/- 13.0 degrees per shoulder movement; p<.01); and (5) impaired ability to flex fingers (range of voluntary flexion of digit III reduced from 107.3 degrees +/-79.6 degrees to 91.4 degrees +/-74.1 degrees; p<.05). CONCLUSION: Lycra garments, designed to produce continuous stretch of spastic muscles when worn for several hours each day, have rapid splinting and antispastic effects on wrist and fingers in patients with hemiplegia. These garments may help severely affected patients with major spasticity or painful swollen limbs.

Adult↗

Potentially reversible cognitive impairment in patients presenting to a memory disorders clinic.

This paper aims to describe a memory disorders clinic (MDC) for the assessment of patients presenting with early cognitive impairment, to examine the predictive utility of laboratory tests conducted on patients with early memory complaints, and, to investigate the potential reversibility of cognitive impairment in 80 consecutive patients presenting to an MDC. Abnormal laboratory results did not significantly correlate with diagnosis at presentation, with presence or absence of cognitive impairment at presentation or at one year follow up, or with cognitive outcome. Thorough assessment of a person presenting with memory impairment is mandatory. We suggest that a routine battery of laboratory investigations be replaced with selected investigations based on clinical indicators only. The term 'reversible dementia' is a misnomer, and we recommend instead the use of 'potentially reversible cognitive impairment'. We argue that the term 'dementia' should only be used to describe cognitive impairment in cases of irreversible degenerative brain disease.

Adult↗

Rehabilitation of a person with severe traumatic brain injury.

A case study report of a long and intensive rehabilitation programme for a young woman after she sustained a severe diffuse axonal injury in a motor vehicle accident is described in detail. The purpose of this paper is to encourage specialist brain injury rehabilitation services to offer extended rehabilitation programmes to patients, even with very severe injuries. Significant functional improvements and enhanced quality of life frequently reward the high cost and hard work involved.

Accidents, Traffic↗

The impact of the organisation of mental health services on the quality of assessment provided to older patients with depression.

OBJECTIVE: The objective of this study was to examine the impact of the organisation of mental health services on the quality of medical and psychiatric assessment provided to patients with depression over 50 years of age. METHOD: A retrospective clinical audit of 99 patients with primary depressive disorders who were over 50 years of age was used. These patients were assessed initially by specialised psychogeriatric outpatient and community services (44%), community-based adult mental health services (35%) or an inpatient service (21%). At 2-3 years follow up, clinical outcomes were rated by treating physicians and included current depression status, cognitive and medical status, course of illness since initial assessment and current living circumstances. RESULTS: Patients who were assessed by the community-based adult mental health service received the least comprehensive assessment. Although these patients were more likely to be living independently, they tended to have the poorest depression outcome. Patients who were assessed by the specialised or inpatient services received more comprehensive initial assessment and better coordinated long-term care. Although these patients had more medical and cognitive comorbidity they had better overall depression outcomes. CONCLUSIONS: Within a service system that determines access according to an arbitrary age of onset, patients with depression receive the best assessment from specialised psychogeriatric services. However, patients with an early age of onset, more chronic disorders and poor outcomes are treated largely within community-based adult services. Psychiatric services need to ensure that all older patients with depression receive appropriate biomedical and psychosocial assessment, as well as continuity of medical and psychological treatment.

Age Factors↗

The effects of a volatile anaesthetic on the excitability of human corticospinal axons.

The recovery of excitability following a conditioning volley and the strength-duration properties of corticospinal axons were measured in 10 neurologically normal patients in whom corticospinal function was being monitored during scoliosis surgery. Corticospinal volleys were produced using transcranial electrical stimulation of the motor cortex, and recorded from the spinal cord using epidural leads. Administration of a volatile anaesthetic, sevoflurane 2%, increased the threshold current required to produce a submaximal test volley by 35.8% (P = 0.0005), indicating that the anaesthetic depressed the excitability of the site at which the transcranial stimulus activated the corticospinal system. Following a strong transcranial stimulus, axons were relatively refractory for conditioning-test intervals up to approximately 2.5 ms, and then superexcitable for intervals of >10 ms. In two patients, the time course and extent of refractoriness and superexcitability did not differ when receiving sevoflurane 2% and after its withdrawal. Strength-duration properties were determined by measuring the stimulus current required to produce a submaximal corticospinal volley of fixed amplitude using test stimuli of different duration, from 50 micros to 1 ms. Strength-duration curves were well described by a hyperbolic function, with which there is a linear relationship between stimulus charge and stimulus duration. In the absence of sevoflurane, the strength-duration time constant (tau(SD)) was 432.2 +/- 70.5 micros. When sevoflurane 2% was administered to 6 patients, tau(SD) decreased to 203.7 +/- 93.8 micros, a change that was significant (P = 0.04). The decrease in tau(SD) was accompanied by an increase in rheobase. These findings imply that the lowest-threshold component of the corticospinal volley produced by transcranial electrical stimulation probably arises from nodes of Ranvier of corticospinal axons, where it would not be affected by changes in the excitability of cortical neurons. It is suggested that the increase in threshold produced by sevoflurane is due to depression of Na(+) currents at the nodes of Ranvier of corticospinal axons.

Adolescent↗

Activity-dependent hyperpolarization and conduction block in chronic inflammatory demyelinating polyneuropathy.

Voluntary activity produces activity-dependent hyperpolarization of the active motor axons. The present study investigated whether this hyperpolarization produces conduction block in chronic inflammatory demyelinating polyneuropathy (CIDP). Studies were performed in 10 healthy control subjects, 7 patients with CIDP, and 3 patients with multifocal motor neuropathy. The compound muscle action potential (CMAP) of the abductor pollicis brevis was recorded in response to supramaximal stimuli to the median nerve at the wrist, alternating with measurements of axonal excitability. After a maximal voluntary contraction for 60 seconds, the amplitude of the maximal CMAP was significantly reduced in symptomatic CIDP patients by 40%, but there were only slight changes in the CMAPs of healthy controls, asymptomatic CIDP patients, and multifocal motor neuropathy patients. In symptomatic CIDP patients, the activity-dependent conduction block paralleled the activity-dependent hyperpolarization and was presumably precipitated by it. In these patients, the safety margin for impulse conduction was estimated to be about 12%. Activity-dependent conduction block may be clinically important in chronic demyelinating diseases and can be demonstrated electrophysiologically if testing occurs across pathological sites.

Action Potentials↗

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Crops, Agricultural↗

Changes in excitability indices of cutaneous afferents produced by ischaemia in human subjects.

1. The present study was undertaken to determine whether mechanisms other than membrane depolarization contribute to the changes in excitability of cutaneous afferents of the median nerve under ischaemic conditions. 2. In six healthy subjects, axonal excitability was measured as the reciprocal of the threshold for a compound sensory action potential (CSAP) of 50% maximal amplitude. Refractoriness and supernormality were measured as threshold changes 2 and 7 ms, respectively, after supramaximal conditioning stimuli. The strength-duration time constant (tauSD) was calculated from the thresholds for unconditioned CSAPs using test stimuli of 0.1 and 1.0 ms duration. Changes in these indices were measured when subthreshold polarizing currents lasting 10 or 100 ms were applied, before, during and after ischaemia for 13 min. 3. At rest, the change in supernormality produced by polarizing currents was greater with the longer polarizing current, indicating that it took up to 100 ms to charge the internodal capacitance. 4. Refractoriness and its dependence on excitability increased more than expected during ischaemia. Supernormality was abolished during ischaemia, and reached a maximum after ischaemia but was then barely altered by polarizing current. tauSD had a similar relationship to excitability before, during and after ischaemia. 5. By contrast, during continuous depolarizing current for 8 min to mimic the depolarization produced by ischaemia, the relationship between excitability and refractoriness was the same during the depolarization as before it. 6. It is suggested that the large increase in refractoriness during ischaemia might be due to interference with the recovery from inactivation of transient sodium channels by an intra-axonal substrate of ischaemia. The post-ischaemic increase in supernormality and the lack of change with changes in axonal excitability can be explained by blockage of voltage-dependent potassium channels.

Action Potentials↗

Evidence for fusimotor drive in stroke patients based on muscle spindle thixotropy.

To study fusimotor function in stroke patients, we compared the amplitude of stretch reflexes elicited in flexor carpi radialis (FCR) after contraction of FCR with the wrist held flexed ('hold-short') or extended ('hold-long'). Seven subjects with impaired hand function and spasticity due to stroke, and seven healthy subjects were investigated. Surface electrodes recorded electromyographic activity of wrist flexors and extensors while subjects performed isometric wrist flexions with the wrist alternately in 15 degrees of flexion or extension. After contractions the wrist was moved passively to the mid-position, and stretch reflexes were elicited via controlled mechanical taps delivered over the FCR tendon. For both groups, the amplitude of the stretch reflex was greater after 'hold-short' than 'hold-long' contractions. This finding is consistent with the 'after-effects' of intrafusal fibre activation, and suggests that fusimotor neurones are activated during voluntary contractions of the paretic limb, just as in the limb of a healthy subject.

Adult↗