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G C Leslie

Publications and source records attributed to G C Leslie.

At least 19 recordsLinked to original sources
PubMed1994

Correlations between dose, plasma concentrations, and antispastic action of tizanidine (Sirdalud).

In a double blind, placebo controlled, cross over study the correlations between single doses (2, 4, and 8 mg), plasma concentrations, and antispastic action of tizanidine were investigated in 16 patients with extensor spasticity of the legs due to multiple sclerosis. An electrogoniometer was used to assess muscle tone at knee extensors, applying Wartenberg's pendulum test. Blood samples, a clinical assessment of muscle tone by the Ashworth scale, and muscle strength by the British Medical Research Council scale were obtained concomitantly. Confirmatory analysis using the change in the relaxation index (R2 value) 1.5 hours after each treatment, showed a statistically significant (p = 0.0123) linear dose-response relation between single doses and antispastic action of tizanidine. Further statistical analysis showed a strong within patient linear correlation between plasma concentrations and antispastic action at 4 and 8 mg doses (p = 0.014 and 0.004 respectively), but only weak between patient correlations. The analysis of the dose-plasma concentration relation showed results consistent with linear pharmacokinetics. The comparison of changes in the R2 ratio with concomitant Ashworth scores showed a significant correlation between the two. It is concluded that there are linear correlations between single doses, plasma concentrations, and antispastic action of tizanidine. Because of the strong within patient but weak between patient correlation between plasma concentrations and antispastic action of tizanidine the effective doses should be determined individually.

Adult↗
PubMed1994

Pharmacokinetics and pharmacodynamics of tizanidine.

The relationship among tizanidine dose, plasma concentration, and antispastic action is linear in nature. Response to a given dose of this agent varies among patients, and determining the appropriate clinical dose requires individual titration.

Clonidine↗
PubMed1989

The effect of EU4093 (azumolene sodium) on the contraction of intrafusal muscle in the soleus muscle of the anaesthetized rat.

1. EU4093 (azumolene sodium) is a direct acting, skeletal muscle relaxant with structural similarities to dantrolene sodium in that the para-nitro phenyl group of dantrolene sodium is replaced by a para-bromo phenyl group. 2. The effect of EU4093 on the twitch of the intact rat soleus preparation is nearly maximal at a dose of 20 mg kg-1. This dose of EU4093 reduces the amplitude of the twitch to 31.9% of the control value. By comparison, dantrolene sodium reduced the twitch amplitude to 31.3% of the control value at a dose of 5 mg kg-1. 3. The contraction of intrafusal muscle as measured by the response of spindle afferent discharge was also reduced by EU4093. 4. The most significant difference between the effect of EU4093 and dantrolene sodium on the contraction of intrafusal muscle was that EU4093 had an appreciable depressant action at high stimulation frequencies at which dantrolene sodium had only a minimal relaxant effect on the intrafusal muscle contraction. 5. The significance of this difference in the actions of EU4093 and dantrolene sodium is discussed in terms of the possible effect of the drug in the intact animal and human patient. It is concluded that, because the discharge frequency is not likely to move into the high frequency range at which dantrolene sodium and EU4093 have significantly different effects, the overall effect of these two drugs is likely to be similar.

Anesthesia↗
PubMed1988

Observations on the applicability of the Wartenberg pendulum test to healthy, elderly subjects.

Wartenberg developed his pendulum test as a simple but precise test to assist examination of muscle tone in patients with Parkinson's disease. It has recently been reintroduced, and computerised, to evaluate spasticity in young hemiplegics. The results are reported on the highly successful application of this computerised test to large numbers of healthy, elderly subjects. The data have provided normal values for a number of measurements. Analysis of variance has shown that differences between individual subjects account for a major part of the total variabilities seen in all measurements taken. Factors such as position, leg and time trend contribute very little to total variation and, for practical purposes, can be ignored.

Adult↗
PubMed1988

Does the Wartenberg pendulum test differentiate quantitatively between spasticity and rigidity? A study in elderly stroke and Parkinsonian patients.

The results of applying the Wartenberg pendulum test to the assessment of muscle tone in populations of stroke and Parkinsonian patients are described. The test was able to distinguish between increased muscle tone of the spastic or rigid type. The Parkinsonian patients showed a marked reduction of the maximum velocity of the leg swing, with the relaxation index tending to a value of about one. In contrast the affected limb of stroke patients showed a lesser reduction of the velocity of the swing, the relaxation index tending to a value of less than one.

Aged↗
PubMed1986

How is ventilation maintained in the presence of the muscle relaxant, dantrolene sodium? A study in the anaesthetized rat.

The effects of intravenous injection of the muscle relaxant dantrolene sodium on ventilation, integrated EMG of external intercostal muscles and motor unit discharge in these muscles were measured in anaesthetized rats. Dantrolene sodium was administered in a carrier solution at pH 10. The carrier was not responsible for the effects seen on dantrolene sodium infusion. Dantrolene sodium (5 mg kg-1 body weight) reduced inspired ventilation (VI) on average from 308 +/- 106 ml min-1 (s.d., n = 8) in the control period to 247 +/- 118 ml min-1 (n = 8) after dantrolene sodium. Expired ventilation was reduced likewise from 274 +/- 132 ml min-1 (n = 8) to 229 +/- 109 ml min-1 (n = 8). These changes are significant at P less than 0.05. The integrated EMG was increased by 40.0 +/- 29.3% (n = 9), a change significant at P less than 0.001. Dantrolene sodium not only decreased the mean interspike interval of individual motor units by 16.2 +/- 11.1% (n = 13), a change significant at P less than 0.001, but also increased the duration of the burst of activity of each individual motor unit on average by 36.2 +/- 52.4% (n = 13), a change significant at P less than 0.05. The recruitment of additional motor units was also effected by dantrolene sodium. These units did not behave in any noticeably different manner from units previously active. It is concluded that the nervous system compensates for the effect of dantrolene sodium only to a limited extent by increasing the frequency of discharge of active motor units. Recruitment ofadditional motor units and increased burst duration play at least as important a role.

Anesthesia↗
PubMed1984

The action of dantrolene sodium on individual fast and slow motor units of the rat anaesthetized with urethane.

Rats, anaesthetized with urethane, were injected intravenously with dantrolene sodium in a vehicle of 5% mannitol taken to pH 10 with NaOH. The muscle relaxant action of dantrolene sodium was measured from the contractions of individual motor units of the extensor digitorum longus (EDL), soleus (SOL) and segmental tail (ST) muscles. Data were also collected from their parent whole muscle preparations. The depressant action of dantrolene sodium on the percentage-normalized amplitude of contraction of the individual motor units was greater than its effect on the whole muscle twitch amplitude, in all three muscles. The twitch amplitude of fast contracting motor units was significantly more reduced (P less than 0.001) by dantrolene sodium than was that of slow contracting motor units. Dantrolene sodium reduced the contraction time of all motor units. The effect of the drug on half-relaxation time varied within and between groups of motor units studied. The drug was confirmed to have a greater depressant action on the twitch contraction than on the fused tetanus of whole muscle. This was true also for single motor units. With tetanic stimulation the effect of dantrolene sodium was also dependent upon the motor unit type, fast or slow. A maximum depression of contractile tension occurred at a stimulation frequency of 64 Hz for fast EDL motor units whereas the maximum depression for ST slow units, the slowest units tested, was at a stimulation frequency of 14 Hz.

Anesthesia↗
PubMed1981

The action of dantrolene sodium on rat fast and slow muscle in vivo.

1. Rats, anaesthetized with urethane, were injected intravenously with dantrolene sodium in a carrier solution of 5% mannitol taken to pH 10 with NaOH. This carrier solution itself was without effect on extrafusal muscle contraction. 2. Dantrolene sodium (5 mg/kg) had a greater depressant action on the twitch contraction of the fast extensor digitorum longus (EDL) muscle than on the slow soleus (SOL) muscle. The EDL twitch was depressed to 25.9% +/- 1.2% (mean + s.e. mean, n = 7) of control whereas the SOL twitch was depressed to 31.3% +/- 0.4% (n = 9). These values were significantly different at the P less than 0.001 level. 3. The twitch contraction time to peak was reduced by approximately 35% in both EDL and SOL by dantrolene sodium. However, the drug reduced the half relaxation time of SOL by approximately 30% but that of EDL was hardly affected. 4. The effect of dantrolene sodium on contractions elicited by repetitive stimulation was dependent upon the stimulation frequency. For the SOL muscle the greater depression was produced at a stimulation frequency of 25 Hz and for EDL at 75 Hz. The minimum of depression was produced for a full fused tetanus for both muscles. 5. The significance of these findings is discussed in terms of the action of dantrolene sodium on motor control in the intact animal.

Animals↗
PubMed1981

The effect of dantrolene sodium on intrafusal muscle fibres in the rat soleus muscle.

1. The action of the skeletal muscle relaxant drug, dantrolene sodium, given intravenously, on the intrafusal fibres of the soleus muscle of the urethane-anaesthetized rat has been investigated. The experiments were made on functionally single spindle afferents and gamma fusimotor fibers isolated in dorsal and ventral roots respectively. 2. Dantrolene sodium was without effect on the discharge of primary and secondary afferents from the passive muscle spindle, nor were the dynamic indices of these endings affected. 3. Intrafusal muscle contraction was measured indirectly by means of the spindle afferent discharge. 4. The intrafusal muscle twitch contraction, as measured by means of the amplitude of the frequencygram, was depressed more slowly to a lesser extent than was the twitch of the extrafusal contraction. 5. Intrafusal contraction resulting from tetanic stimulation of the gamma fibre was depressed by dantrolene sodium to an extent dependent upon the stimulation frequency. At frequencies of 10, 25 and perhaps 50 Hz the depression was complete, that is, no afferent response was evoked; at 200 Hz stimulation, the depression was minimal (or non-existent). 6. For a muscle spindle primary ending under dynamic gamma activation dantrolene sodium caused a reduction of dynamic index whereas for the ending under static activation it caused an increase. 7. The significance of the findings in terms of the clinical use of the drug is considered.

Action Potentials↗
PubMed1978

Some observations on the efferent innervation of rat soleus muscle spindles.

In the small segmental tail muscles of the rat beta fibres provide exclusively the dynamic fusimotor control, while gamma fibres provide exclusively the static fusimor control. The present experiments were made to investigate the fusimotor innervation of spindles in a large muscle of the rat, the soleus, and thus to determine the occurrence and significance of beta innervation in this muscle. Our results have revealed no case of beta innervation in the rat soleus. As a consequence of our experimental method, however, we would not claim that beta innervation does not exist in the soleus, only that it must play an insignificant role relative to that seen in the tail segmental muscles. Investigations of the fusimotor innervation of eight spindles were sufficiently complete to warrant detailed illustration. The number of gamma fibres ranged from two to four. In every case the slowest conducting gamma fibre was dynamic. However, the conduction velocity spectra for the static and dynamic gamma fibres to rat soleus overlap to such an extent that it is impossible to use conduction velocity as the sole guide to functional gamma fibre classification. The pooled results from the eight spindles fully investigated provide a ratio of static to dynamic gamma fibres of approximately 1:1. Other evidence discussed in the paper suggests that in the muscle nerve the ratio is considerably higher. These differences are reconciled if the dynamic gamma fibres branch more profusely and innervate more spindles than do the static gamma fibres.

Animals↗
PubMed1978

A low pass filter with amplifier for measurement of active and passive tensions of skeletal muscle in vitro.

When displaying and measuring passive and active twitch tensions developed by skeletal muscle in vitro, the problems of amplification may be resolved by recording two traces. One, recorded at relatively low gain, is used for measurements of twitch tension amplitude. The other, recorded simultaneously, is a modified version of the first trace, in which the voltage signals are passed through a suitably constructed low pass filter, amplified and displayed. This second trace, recorded at relatively high gain, is used for measurements of changes in passive tension and contracture responses of relatively small amplitude.

Amplifiers, Electronic↗