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Biomedical subjects

R W Marshall

Publications and source records attributed to R W Marshall.

At least 37 records · Page 2Linked to original sources

Neurotransmitter feedback is not important in modulating the noradrenergic component of responses of rat vas deferens to twin pulse electrical field stimulation.

1. Drug effects on the full time-course of tension responses of the rat vas deferens to challenges of twin pulse field stimulation (TPFS) were examined. A microprocessor-controlled system was used to regulate stimulus delivery, on-line data collection and subsequent data analysis. 2. The second, noradrenergic phase of the response to the second stimulus of TPFS was missing when the interpulse interval was set at 3 s but was progressively restored as the interpulse interval was extended to 120 s. 3. With a 3 s interpulse interval, the missing second phase of the response to the second stimulus was not restored by the selective alpha 2-adrenoceptor antagonists yohimbine, imiloxan or idazoxan, indicative that alpha 2-adrenoceptor-mediated feedback inhibition of noradrenaline release is not the predominant mechanism modulating this response component. 4. Incubation with the P1-purinoceptor antagonist 8-phenyl-theophylline also failed to restore the missing noradrenergic component in the response to the second stimulus of TPFS. 5. Nevertheless, both responses to TPFS were impaired by the selective alpha 2-adrenoceptor agonist clonidine and by the P1-purinoceptor agonist 2-chloroadenosine, indicating the presence of functional presynaptic receptors of both types. These agonist-induced inhibitory effects were readily reversed by those antagonists which had failed to restore the missing noradrenergic component in the second response to TPFS.

Adrenergic alpha-Agonists↗

Separation of putative alpha 1A- and alpha 1B-adrenoceptor mediated components in the tension response of the rat vas deferens to electrical field stimulation.

1. The effects of the putative alpha 1B-adrenoceptor antagonist, chloroethylchlonidine (CEC), on tension responses of the rat isolated whole vas deferens to single and multiple pulses of electrical field stimulation have been evaluated by use of a microcomputer system which enables the averaging of like-responses throughout their time course. 2. CEC (10(-7) to 3 x 10(-6) M) selectively and in a concentration-dependent manner blocked the noradrenergic component of the response to a single field stimulus in the absence or presence of nifedipine (10(-5) M, which blocked the purinergic but not the noradrenergic component of the response). The concentration-response curve of the vas to exogenously-applied noradrenaline (NA) was unaffected by CEC (10(-6) M) but was flattened by nifedipine (10(-5) M). 3. The tension response to 10 Hz trains of pulses was biphasic, with an early (less than 2 s) and a plateau (greater than 4 s) phase. We deduce from our pharmacological analysis that the early phase contains a putative alpha 1B-adrenoceptor component (susceptible to CEC or prazosin but not to nifedipine) and a P2-purinoceptor component (susceptible to suramin or nifedipine) whereas the plateau phase contains an alpha 1A-adrenoceptor component (susceptible to prazosin or nifedipine but not to CEC) and a P2-purinoceptor component (susceptible to suramin or nifedipine). 4. We suggest that the putative alpha 1B-adrenoceptors may be functionally confined to the synaptic region whereas the putative alpha 1A-adrenoceptors are excluded from this region. Trains of pulses would allow NA to accumulate and spill out beyond the synaptic region to reach and activate the putative alphalA-adrenoceptors.

Animals↗

Evidence for involvement of nitric oxide in the non-adrenergic non-cholinergic (NANC) relaxation of human lower oesophageal sphincter muscle strips.

Electrical field stimulation of circular muscle strips from human lower oesophageal sphincter reveals a predominant relaxation response. This relaxation is non-adrenergic non-cholinergic (NANC). The nitric oxide synthesis-blocking agent N omega-nitro-L-arginine (10-100 microM) reduces or abolishes this NANC relaxation, suggesting involvement of nitric oxide in the response.

Adrenergic Fibers↗

The detection of artefacts in EEG series.

In a clinical trial of an anticonvulsant drug, series of electroencephalogram readings are sometimes obtained. These may contain artefacts, that is patches of atypical values which must be identified and either removed or compensated for before a full analysis can be carried out. Methods for identifying such artefacts are discussed. These include non-parametric methods and also parametric ones combining the ideas of autoregressive modelling and of influence in regression. These methods are described and illustrated on typical data sets.

Artifacts↗

Effect of low concentrations of nitrous oxide and isoflurane on peak velocity of saccadic eye movements.

Peak velocity of saccadic eye movements was studied in six healthy volunteers who were each given, on separate days, 5% and 10% MAC of nitrous oxide (5% and 10% end-tidal) or of isoflurane (0.06% and 0.12% end-tidal) or air, each gas for 25 min. Subjective assessment following each treatment was also undertaken. No significant difference was found between air and either 5% or 10% nitrous oxide. However, significant differences occurred at 15 and 25 min after 0.06% isoflurane compared with air (P less than 0.05) and highly significant differences were present 5, 15 and 25 min after 0.12% isoflurane when compared with air and nitrous oxide (P less than 0.01). In contrast, there was little difference between the three gases by subjective assessment.

Adult↗

Effects of low concentrations of cyclopropane and halothane on peak velocity of saccadic eye movements.

We have investigated the effect of 4.7 and 8.8% MAC of cyclopropane, and 5.3 and 9.3% MAC of halothane on the peak velocity of saccadic eye movements (PSV) in six healthy volunteers. Both concentrations of cyclopropane and halothane significantly depressed PSV (P less than 0.01) compared with air, in a dose-related fashion. Halothane depressed PSV significantly more than cyclopropane (P less than 0.05). PSV returned to baseline within 5 min after discontinuation of the agents. There was no significant difference between cyclopropane, halothane and air in subjective assessment of sedation.

Adult↗

Tremor in Parkinson disease: acute response to oral levodopa.

A single blind placebo-controlled study has been performed in order to investigate objectively the acute tremorolytic effect of oral L-Dopa in ten parkinsonians chronically treated with L-Dopa. Finger tremor was assessed by means of a computerized accelerometer method, at rest and during maintenance of a fixed posture. Both resting and postural tremor were significantly influenced by L-Dopa. An "acute test" with oral L-Dopa, especially when different tremor components are investigated, may be useful for identifying objectively parkinsonians whose tremor does not respond to drug therapy or shows a deterioration of drug-responsiveness.

Administration, Oral↗

A surgical approach to the cervicothoracic spine.

We describe a method for approaching the lower cervical and upper thoracic spine, the brachial plexus and related vessels. The method involves the elevation of the medial corner of the manubrium, the sternoclavicular joint, and the medial half of the clavicle on a pedicle of the sternomastoid muscle. We have used this exposure in 17 cases with few complications and good results. Its successful performance requires high standards of anaesthesia, surgical technique and postoperative care.

Adult↗

The effect of theophylline on thyrotoxic tremor.

1. The effect of intravenous aminophylline on theophylline-induced tremor were studied in six hyperthyroid patients before and after treatment to euthyroidism. 2. Baseline tremor power was significantly greater in the hyperthyroid compared with the euthyroid state (P less than 0.05). 3. Aminophylline produced a significantly greater increase in tremor power in the hyperthyroid compared with euthyroid state. 4. There was a significant increase in plasma theophylline clearance and reduction in t1/2 elimination when patients were hyperthyroid but volume of distribution did not change. 5. Intravenous aminophylline potentiates the tremor produced in hyperthyroidism despite an increase in plasma theophylline clearance. A pharmacodynamic mechanism is therefore likely.

Aged↗

Operations to restore elbow flexion after brachial plexus injuries.

We have reviewed 50 patients at a mean period of 2.7 years after operations to restore elbow flexion lost as a result of traction injuries of the brachial plexus. A variety of operations were used and, in general, patient satisfaction was high. Objectively, however, the power in the transferred muscles was poor; less than half of the patients had a significant improvement in function. Poor control of the shoulder often compromised the result. Latissimus dorsi and triceps transfers proved most reliable, and some Steindler flexorplasties also gave satisfactory results. Pectoralis major transfers were disappointing and we do not recommend their use in women.

Adolescent↗

Effect of drugs, hormones and electrical field stimulation on isolated muscle strips from human choledochoduodenal junction.

The behaviour of in vitro strips from the human choledochoduodenal junction would appear to be related to the anatomical location of origin of the strip. Strips from the papillary region showed low tone and obvious spontaneous rhythmic contractions (0 X 5-6/min). Strips from the region of the inferior choledochal sphincter showed, in ten out of fifteen specimens, spontaneous myogenic tone and gave a relaxation or a biphasic response (relaxation followed by contraction) to electrical field stimulation (0 X 3 ms pulses at 10 Hz for 5 s). All strips from human choledochoduodenal junction are remarkably insensitive to a variety of gastrointestinal hormones and to opioid agents.

Acetylcholine↗

Human cognitive function following binedaline (50 mg and 100 mg) and imipramine (75 mg): results with a new battery on tests.

The effects of two single oral doses of binedaline (50 and 100 mg), imipramine (75 mg) and placebo were compared on a range of psychological tasks (logical reasoning, the Stroop test, and five-choice serial reaction) in healthy young volunteers. The tasks, together with a mood adjective check-list, were completed prior to drug administration and 1, 2, 4 and 8 h post-dose. Binedaline had no significant effect on any of the task parameters. Imipramine impaired performance on all but the Stroop test at 2 h after drug administration. At 1, 2 and 4 h, ratings on the "deactivation" dimension of the mood adjective check-list were significantly higher following imipramine when compared to placebo. The results are discussed in terms of some general considerations about the selection and scoring of tasks to be used in the screening of drugs.

Adult↗

Computerised axial tomography in traction injuries of the brachial plexus.

Severe traction injuries may damage the brachial plexus at any level from the spinal cord to the axillary outlet. Investigation aims to determine the level of the injury for each of the nerves, trunks or cords, with particular reference to obtaining firm evidence of any intradural (pre-ganglionic) damage. We report the results of computerised axial tomography of the cervical spine in comparison with conventional myelography and with surgical exploration of the plexus. CT scanning with contrast enhancement greatly improves diagnostic accuracy, particularly at C5 and C6 root levels.

Acute Disease↗

Exercise-induced hand tremor: a possible test for beta 2-adrenoceptor selectivity in man?

The effects of intravenous doses of propranolol, sotalol, timolol, atenolol and placebo on exercise-induced tachycardia and exercise-induced increases in hand tremor were assessed in four healthy volunteers. All active drugs produced significant reductions in exercise-induced tachycardia. Exercise caused consistent significant increases in hand tremor which were blocked by the three non-cardioselective drugs but not by atenolol or placebo. The blockade of exercise-induced hand tremor is suggested as a possible test for the assessment of the selectivity of beta-adrenoceptor blockade in man.

Adrenergic beta-Antagonists↗

Tremor: an alternative approach for investigating adrenergic mechanisms in thyrotoxicosis?

The effects of nadolol (or placebo) and carbimazole on thyrotoxic tremor were investigated in 18 thyrotoxic patients. Both nadolol and carbimazole produced significant reductions in tremor power although nadolol did not cause any change in serum free tri-iodothyronine and free thyroxine concentrations. The results are discussed in terms of the pathogenesis of thyrotoxic tremor and the potential usefulness of tremor in the investigation of adrenergic mechanisms in thyrotoxicosis.

Adrenergic beta-Antagonists↗

The tremorolytic action of beta-adrenoceptor blockers in essential, physiological and isoprenaline-induced tremor is mediated by beta-adrenoceptors located in a deep peripheral compartment.

The effects of intravenous propranolol 100 micrograms kg-1, sotalol 500 micrograms kg-1, timolol 7.8 micrograms kg-1, atenolol 125 micrograms kg-1 and placebo on essential, physiological and isoprenaline-induced tremor were studied. These beta-adrenoceptor blocker doses produced equal reduction of standing-induced tachycardia in essential tremor patients. Atenolol produced significantly less reduction of essential and isoprenaline-induced tremor than the non-selective drugs, confirming the importance of beta 2-adrenoceptor blockade in these effects. Propranolol and sotalol produced equal maximal inhibition of isoprenaline-induced tremor but propranolol was significantly more effective in reducing essential tremor. The rate of development of the tremorolytic effect was similar in essential, physiological and isoprenaline-induced tremors but all tremor responses developed significantly more slowly than the heart rate responses. It is proposed that these results indicate that the tremorolytic activity of beta-adrenoceptor blockers in essential, physiological and isoprenaline-induced tremor is exerted via the same beta 2-adrenoceptors located in a deep peripheral compartment which is thought to be in the muscle spindles.

Adrenergic beta-Antagonists↗

Comparison of the effects of therapeutic doses of meptazinol and a dextropropoxyphene/paracetamol mixture alone and in combination with ethanol on ventilatory function and saccadic eye movements.

The respiratory and psychomotor effects of a single oral dose of meptazinol (200 mg) and dextropropoxyphene (65 mg)/paracetamol (650 mg) mixture, was compared alone and in combination with ethanol (0.8 g kg-1). Peak saccade velocity following meptazinol or the dextropropoxyphene/paracetamol mixture was not significantly different from placebo. When each of the treatments was followed by ethanol administration, a significant decrease in saccade velocity (P less than 0.01) was seen. Given alone, neither of the analgesic drugs produced a significant change in the slope of the ventilatory response to hypercapnia. Ethanol did not affect the ventilatory response to hypercapnia when given alone or in combination with meptazinol, but when given with the dextropropoxyphene/paracetamol mixture, a significant reduction in the slope of the ventilatory response to hypercapnia occurred at 1.5 h (P less than 0.05) and 2 h (P less than 0.01) after administration of the analgesic drug. No pharmacokinetic interaction was demonstrated between ethanol and meptazinol or the dextropropoxyphene/paracetamol mixture in the doses used. In contrast to meptazinol, the dextropropoxyphene/paracetamol mixture interacts with ethanol on the ventilatory function.

Acetaminophen↗