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Biomedical subjects

R W Clarke

Publications and source records attributed to R W Clarke.

At least 19 recordsLinked to original sources
PubMed1992

An analysis of adrenergic influences on the sural-gastrocnemius reflex of the decerebrated rabbit.

The sural-gastrocnemius reflex was observed in decerebrated rabbits during intrathecal application of four alpha-adrenoceptor antagonists. Idazoxan and yohimbine, which are antagonists at the alpha 2-receptor, caused facilitation of the reflex, although idazoxan was more potent and produced a larger overall increase in the reflex response. However, when given after yohimbine, idazoxan elicited no further increase in reflex responses. The differences between the two drugs may result from the interaction of yohimbine with receptors for 5-hydroxytryptamine. The selective alpha 1-receptor antagonist prazosin had no consistent effects when given alone, but reduced the facilitatory effects of idazoxan. The putative selective post-junctional alpha 2-receptor blocker SK&F 104078 had no significant effects when given alone, nor did it influence the facilitatory action of a subsequent dose of idazoxan. Section of the spinal cord in the presence of idazoxan always caused a decrease in gastrocnemius responses to sural nerve stimulation. These data show that the facilitatory effects of idazoxan are almost certainly mediated at the spinal cord and that they do not involve blockade of alpha 1-receptors. It appears that idazoxan acts by blockade of adrenergic descending inhibition in combination with increased descending facilitation. The inhibition is probably mediated through noradrenaline acting at alpha 2-receptors, and the facilitation may be the result of release of noradrenaline (acting at alpha 1-receptors) and 5-hydroxytryptamine in the spinal cord.

Adrenergic alpha-Antagonists↗
PubMed1992

Prolonged potentiation of transmission through a withdrawal reflex pathway after noxious stimulation of the heel in the rabbit.

The sural-gastrocnemius reflex of the spinalized rabbit was potentiated to an average of 3-6 times control levels after the application of noxious mechanical, thermal or chemical stimuli to the skin of the heel. Facilitation of the reflex was maximal within 1 min of the noxious stimulus, and in many cases persisted for more than 1 h. Prolonged increases in the excitability of the sural-gastrocnemius reflex were not seen after innocuous mechanical or thermal stimulation of the heel. Repetitive electrical stimulation of the sural nerve (100 shocks given at 0.5 Hz) caused persistent facilitation of the reflex when small myelinated A delta fibres or non-myelinated C-fibres were recruited by the conditioning stimulus. Such protracted increases in the excitability of the sural-gastrocnemius pathway would enhance the protective functions of this reflex. The mechanisms described here have probably evolved to provide a high level of reflex protection to the heel after tissue damage has occurred at that site.

Animals↗
PubMed1992

Squamous carcinoma of the head and neck in the young adult.

We present a series of 2305 previously untreated histologically proven squamous carcinomas of the mucosal surfaces of the upper aerodigestive tract managed by one of us in a 27-year period. 62 (2.7%) of the patients were aged 40 years or younger. The sex ratio between young and old patients was similar but, as expected, the younger patients were in better physical condition. Furthermore, 90% of young patients were treated, compared with only 78% of the older patients. Younger patients had a higher incidence of oropharyngeal tumours and lymph node metastases, but the proportion of poorly differentiated tumours, and stage T3-T4 tumours, was similar, as was the metastatic rate. The crude survival of the younger patients was 10% better than that of the older group, and adjusted (life-table) survival was 9% better, and this better survival in younger patients was significant when differing site incidence and N-stage were allowed for by multivariate analysis. The recurrence rate at the primary site was 19% in the younger patients and 15% in older patients, but this difference was not significant. The recurrence rate in cervical lymph nodes was similar in both age groups: 37% at 2 years in young patients and 38% in older patients.

Adult↗
PubMed1992

The role of mucosal receptors in the nasal sensation of airflow.

50 subjects were admitted into a randomized double-blind placebo controlled cross-over trial with 4% lignocaine as the active drug and normal saline as the placebo. Each subject had 2 ml of solution sprayed into each nasal cavity and all subjects had both sprays but on different occasions. The order in which the sprays were administered was randomized. The subjective sensation of nasal airflow was measured using a visual analogue scale before and after the spray. These measurements were made under conditions of the same airflow rate, which was monitored throughout the experiment using a reprogrammed NR6 rhinomanometer. Objective nasal patency was measured as peak nasal inspiratory flow rate. It was found that the nasal sensation of airflow decreased slightly after both lignocaine (difference between medians 5.0; 95% confidence interval -2.91 to 6.11) and normal saline (difference between medians 6.0; 95% confidence interval -1.02 to 7.21). Nonparametric analysis of variance showed this difference to be non-significant (P = 0.73). In addition there was no significant change in objective nasal patency. The results suggest that nerve endings in the nasal mucosa play no part in sensing nasal airflow during respiration.

Adolescent↗
PubMed1992

Nasal airflow receptors: the relative importance of temperature and tactile stimulation.

The receptors responsible for the nasal sensation of airflow have not been identified with certainty. Although both mechanoreceptors and thermoreceptors have been implicated, evidence suggests that the nose is more sensitive to cold air than to air at body temperature. The present study was designed to investigate the relationship between the velocity and the temperature of an airjet as regards its ability to stimulate the nasal lining. Both the nasal vestibule and the nasal cavum are more sensitive to cold air than to air at mean intranasal temperature (P < 0.001). A similar effect is seen with warm air which is as stimulating as cold air. The nasal vestibule is twice as sensitive as the nasal cavum to an airjet at mean intranasal temperature (P < 0.001). It is concluded that the nasal vestible is very sensitive to the tactile stimulation of an airjet. This effect is highly temperature dependent being much more pronounced for air temperatures above or below the mean intranasal temperature. The temperature effect is relatively more important in the nasal cavum which is very much less sensitive to stimulation than the vestibule.

Adult↗
PubMed1992

Neck dissection for non-squamous malignancy.

Of 1030 patients who underwent neck dissection (radical, modified or selective) in a 27-year period 103 had malignant neck nodes from a primary site in the head and neck with a histological diagnosis other than squamous carcinoma. There were 71 men and 32 women in this group with a mean age of 55 years. 28 patients had neck dissection as part of their initial treatment and 75 for later nodal recurrence. Five-year survival was 52% (40-63%). Survival was site dependent, best for thyroid tumours and worst for tumours of the major salivary glands (chi 1(2) = 6.52, P < 0.05). Histology significantly affected survival, best for papillary tumours and worst for melanoma and undifferentiated tumours (chi 1(2) = 3.85, P < 0.05). Survival was worse with advanced N stage but varied little with node level. The number of nodes invaded had a highly significant effect on survival (chi 4(2) = 23.94, P < 0.001), but extracapsular rupture had no effect. Advanced T stage at the time of surgery had a significant adverse effect on survival using univariate analysis, but this effect disappeared using multivariate analysis. In the 75 patients who had neck dissections for nodal recurrence the presence of a simultaneous recurrence at the primary site had no significant effect on survival. These patients had a better 5-year survival than patients having neck dissection for squamous disease, but the usual predictors of survival in squamous carcinoma do not always apply to non-squamous malignancy.

Female↗
PubMed1992

Opioidergic inhibition of flexor and extensor reflexes in the rabbit.

1. Recordings were made from gastrocnemius medialis (GM), semitendinosus (ST) and tibialis anterior/extensor digitorum longus (TA/EDL) motor nerves during mechanical and electrical stimulation of the skin of the foot in decerebrated and spinalized rabbits. 2. GM motoneurones were excited from the heel and not from the toes, whereas TA/EDL responded to stimulation at the toes but not at the heel. ST also responded to electrical and mechanical stimulation at the toes, but there was a disparity between the effects of the two types of stimuli when they were applied at the heel: ST motoneurones fired in response to electrical stimulation of the heel but showed only an 'off' response to mechanical stimulation at this site. 3. The opioid antagonist naloxone caused a dose-dependent increase in all reflexes evoked by electrical stimulation of the skin. The heel-GM, toes-ST and toes-TA/EDL reflexes all increased to more than 3 times control levels with naloxone, which also caused significant decreases in the latencies of these reflex responses. On the other hand, the heel-ST response increased to just 1.4 times control levels and showed no decrease in latency with the opioid antagonist. 4. These data suggest that segmental withdrawal reflex pathways in the rabbit are suppressed by endogenous opioid peptides. This opioid-mediated inhibition seems to operate non-selectively on reflex pathways between cutaneous afferents and motoneurones.

Animals↗
PubMed1991

The effects of midlumbar spinal cord section on opioidergic modulation of the sural-gastrocnemius reflex of the rabbit.

In decerebrated rabbits spinalized at the thoraco-lumbar junction, crushing the spinal cord between segments L4 and L5 resulted in enhancement of the sural-gastrocnemius reflex. After midlumbar crush, naloxone increased the reflex response to significantly greater levels than observed in earlier experiments in rabbits with only a low thoracic spinal section. Naloxone-reversible, stimulus-evoked inhibition of the reflex response was not affected by midlumbar crush. These findings show that neurones in midlumbar segments of the spinal cord do not contribute to opioidergic modulation of the sural-gastrocnemius reflex.

Animals↗
PubMed1991

Opioidergic inhibition of reflexes evoked by selective stimulation of sural nerve C fibres in the rabbit.

Reflexes were evoked in the gastrocnemius medialis (GM) muscle nerve by selective electrical stimulation of the non-myelinated C fibres of the ipsilateral sural nerve of decerebrated, spinalized rabbits. The opioid antagonist (-)-quadazocine (555 micrograms/kg i.v.) enhanced responses to sural C fibre stimulation to an average of 236% of pre-drug levels. In addition, C fibre-evoked reflexes were depressed for 7-9 min after repetitive activation of the high threshold axons of the common peroneal nerve, and this effect was reversed after quadazocine. Thus, GM responses to stimulation of non-myelinated sural afferent fibres are suppressed by endogenous opioid peptides, but the degree of inhibition does not appear to be as profound as that previously reported for reflexes evoked by myelinated fibres.

Animals↗
PubMed1991

Prolonged inhibition of a spinal reflex after intense stimulation of distant peripheral nerves in the decerebrated rabbit.

1. In decerebrated rabbits, repetitive stimulation of the high-threshold afferents of the left common peroneal (CP) nerve evokes prolonged depression of the sural-gastrocnemius medialis (GM) reflex recorded in the same limb. This inhibition is antagonized by co-administration of the opioid antagonist naloxone with the alpha 2-adrenoceptor antagonist idazoxan. The present study was designed to investigate whether such inhibition could be elicited from the contralateral hindlimb or the forelimbs. 2. The sural-GM reflex of decerebrated rabbits was depressed for more than 15 min after stimulation of either ipsilateral or contralateral common peroneal (CP) or median nerves with 500 pulses of 20 V, 1 ms given at 5 Hz. The order of efficacy for generating this inhibition was ipsilateral CP greater than contralateral CP greater than or equal to ipsilateral median = contralateral median. In three of thirty-nine rabbits, stimulation of the median nerves caused facilitation of the sural-GM reflex. 3. Idazoxan (1-2 mg/kg I.V.) did not significantly alter the depressant effect of ipsilateral CP stimulation but reduced that evoked by either median nerve and almost abolished the inhibition evoked from the contralateral CP nerve. 4. Naloxone (0.25 mg/kg I.V.) reduced the effects of ipsilateral CP stimulation, did not alter the inhibition evoked from contralateral CP, and had equivocal actions on the responses to median nerve stimulation. 5. When given together, the two antagonists almost abolished the effects of stimulating the median nerves and the contralateral CP nerve, and markedly reduced the inhibition evoked from the ipsilateral CP nerve. 6. These data show that prolonged inhibition of the sural-GM reflex can be evoked by stimulation of nerves in all four limbs and that in each case the inhibition can be blocked or reduced by co-administration of antagonists to opioid and alpha 2-adrenergic receptors. Such persistent inhibition of reflexes may serve to inhibit withdrawal reflexes in situations where interruptions to normal movement would be disadvantageous.

Adrenergic alpha-Antagonists↗
PubMed1990

Release and spread of immunoreactive neurokinin A in the cat spinal cord in a model of acute arthritis.

Antibody microprobes were used to study the release of immunoreactive neurokinin A into the spinal cord of anaesthetised cats during and following injection of a knee joint with kaolin and carrageenan. A basal level of immunoreactive neurokinin A was detected prior to any noxious stimuli. Innocuous mechanical joint stimuli (flexion or pressure) did not alter this basal level of release. However, on injection of kaolin and carrageenan into a knee joint, evidence of release into the ipsilateral spinal cord was immediately observed. Initially, immunoreactive neurokinin A was detected in 2 regions: one at the dorsal surface of the spinal cord and the other centred on the superficial dorsal horn. Within 1 h of joint injection, however, immunoreactive neurokinin A was detected throughout the dorsal horn and the adjacent white matter. The extensive spread and persistence of immunoreactive neurokinin A in the spinal cord may underlie some of the prolonged excitability changes evoked by brief noxious stimuli and peripheral inflammation reported by other laboratories.

Acute Disease↗
PubMed1990

Noxious stimulation of the toes evokes long-lasting, naloxone-reversible suppression of the sural-gastrocnemius reflex in the rabbit.

Repetitive stimulation of the small myelinated and non-myelinated afferents of the common peroneal (c.p.) nerve evokes a long-lasting (20-25 min), naloxone-reversible inhibition of the sural-gastrocnemius reflex in the decerebrated and spinalized rabbit. Altering the number and frequency of stimuli applied to the c.p. nerve showed that this inhibition was dependent on temporal summation of afferent input from that nerve, and that the optimum frequency for producing the effect was between 2 and 10 Hz. Application of natural conditioning stimuli in and around the receptive field of the c.p. nerve showed that noxious, but not innocuous, mechanical and thermal stimuli could evoke long-lasting inhibition of the sural-gastrocnemius reflex. Thermal stimuli produced a biphasic change in the excitability of the reflex with facilitation followed by inhibition. The opioid antagonist naloxone (250 micrograms.kg-1) blocked all suppression resulting from these natural noxious stimuli. Chemical stimulation of the skin with mustard oil did not evoke naloxone-reversible inhibition of the reflex. These results indicate that intensely noxious stimuli can promote the release of opioid peptides in the spinal cord, and that one of the functions of these peptides may be to regulate the level of excitability in withdrawal reflex pathways.

Animals↗
PubMed1990

The thresholds of the jaw-opening reflex and trigeminal brainstem neurons to tooth-pulp stimulation in acutely and chronically prepared cats.

Electrical stimuli were applied to tooth-pulp in cats and the thresholds of the jaw-opening reflex and of neurons in the trigeminal sensory nuclei were determined. The effects of the method of preparation of the animal for stereotaxic recording were determined by making observations on animals set up in one of three ways: acutely in the usual manner; chronically, three to five days before recording; and acutely with precautions to minimize nociceptive input to the central nervous system. The threshold of the jaw-opening reflex increased progressively during the setting up of the normal, acute preparations and at the time brainstem recording began was significantly higher in these than in either the chronic or low-trauma acute preparations. Previous studies have shown that the increase in threshold is maintained for several hours and is not due to the effects of the anaesthetic. In normal acute preparations, few units (27/154) were found that had thresholds below 50 microA, 0.1 ms, whereas many units were encountered that responded to such a stimulus in chronic (147/152) and low-trauma acute (99/127) animals. In the chronic and in low-trauma acute preparations, there was no significant difference between the thresholds of the units in the main sensory trigeminal nucleus and spinal subnucleus oralis compared with those in subnucleus caudalis. Thus the preparation of an animal for stereotaxic recording can cause a severe and long-lasting depression in the excitability of neurons in the trigeminal sensory nuclei and an increase in the threshold of the jaw-opening reflex. This effect will have influenced the results of previous studies on the responses evoked in central neurons by stimulation of tooth-pulp, and may have similarly affected recordings from other regions.

Anesthesia↗
PubMed1989

Activation by high intensity peripheral nerve stimulation of adrenergic and opioidergic inhibition of a spinal reflex in the decerebrated rabbit.

The short-latency sural to gastrocnemius reflex in the decerebrated rabbit was depressed for 20-30 min following high intensity conditioning stimulation of the common peroneal nerve. This effect was observed in animals with or without spinal section, but was greater in non-spinalized preparations. Graded conditioning stimuli showed that it was necessary to activate fine myelinated common peroneal axons to inhibit the reflex. In spinalized rabbits, maximal inhibition was achieved with conditioning stimulation of fine myelinated axons and was completely reversed by the opioid antagonist naloxone. In non-spinalized rabbits, maximal inhibition was only obtained with conditioning stimuli which activated non-myelinated axons. In these preparations the effects of common peroneal nerve stimuli were only blocked by co-administration of naloxone with the alpha 2-adrenoceptor antagonist idazoxan. Thus high intensity peripheral nerve stimuli activated a segmental opioidergic and a supraspinal adrenergic suppression of the sural-gastrocnemius withdrawal reflex. Such long-lasting suppression of reflex excitability may contribute to recovery from intensely noxious stimuli.

Action Potentials↗
PubMed1989

Reflex actions of selective stimulation of sural nerve C fibres in the rabbit.

Selective electrical stimulation of the non-myelinated C fibres of the sural nerve in the decerebrated, spinalized rabbit evoked long-latency (76-160 ms), long-lasting (greater than 100 ms) reflex responses in the ipsilateral ankle extensor gastrocnemius medialis (GM). Activation of the same fibres elicited little or no response from the ipsilateral knee flexor semitendinosus (ST). Reflex responses were evoked in both GM and ST muscle nerves by stimulation of the A beta afferents of the sural nerve. The A beta-elicited reflex in GM was enhanced, and that in ST depressed by prior activation of sural nerve C fibres. Strychnine, but not picrotoxin or mecamylamine, blocked C fibre-induced inhibition of the flexor reflex. Pinching the heel with serrated forceps produced an immediate reflex discharge in GM motoneurones, whereas ST responded upon termination of the stimulus. Pinching the second toe evoked reflex activity in ST but not in GM. After strychnine (0.5 mg kg-1), both sets of motoneurones responded simultaneously to stimulation of either the heel or the toe. These data show that sural and other afferent fibres from the heel excite ipsilateral GM motoneurones and inhibit ST reflex responses. One interpretation of these findings is that fine sural afferents activate parallel inhibitory and excitatory pathways, of which the former is sensitive to strychnine and therefore probably mediated by glycine.

Afferent Pathways↗
PubMed1988

Thyrotropin releasing hormone, cholecystokinin and endogenous opioids in the modulation of spinal reflexes in the rabbit.

Electrical stimulation of the sural nerve of the rabbit evokes reflexes in the ipsilateral ankle extensor gastrocnemius medialis and in the knee flexor semitendinosus which are differentially modulated by endogenous opioids. Intravenous injection of the putative functional opioid antagonist, thyrotropin releasing hormone (TRH) or its analogue RX77368, caused the extensor response to double in size and the flexor reflex to increase to 1.5-1.7 times pre-drug controls. The opioid RX77368 had no effect on the naloxone-reversible inhibition of the gastrocnemius reflex which followed tetanic stimulation of the fine afferent fibres of the common peroneal or sural nerves. The cholecystokinin antagonist proglumide, which has been shown to enhance the actions of endogenous opioids in some species, had no effects on either reflex. It is possible that TRH acts as an excitatory neurotransmitter or modulator in the spinal cord of the rabbit opposing, but not blocking, the actions of endogenous opioids.

Animals↗
PubMed1988

Adrenergic and opioidergic modulation of a spinal reflex in the decerebrated rabbit.

1. In the decerebrated and spinalized rabbit, electrical stimulation of the sural nerve evokes a short-latency reflex in the ipsilateral ankle extensor gastrocnemius medialis (GM) which is tonically suppressed by endogenous opioids. In the present study we have investigated the inhibitory influences affecting this reflex in non-spinalized, decerebrated rabbits. 2. In non-spinalized rabbits, the thresholds and latencies of the sural-GM reflex were significantly higher than in spinalized preparations. The opioid antagonist naloxone and the alpha-adrenoceptor antagonist idazoxan potentiated the reflex in both preparations. Naloxone was significantly more effective in spinalized rabbits whereas idazoxan had a much larger effect in non-spinalized animals. 3. When the spinal cord was sectioned in the presence of naloxone alone, the GM reflex always increased in size. An ipsilateral hemisection of the cord was as effective as total section in this respect. When the section was performed in the presence of idazoxan and naloxone, the response usually decreased in size. 4. The alpha 2-adrenoceptor agonist clonidine depressed the reflex in spinalized rabbits, an action that was reversed by idazoxan but not by naloxone. 5. These data show that in the decerebrated, non-spinalized rabbit, the sural-GM reflex is tonically suppressed by endogenous opioids, presumably acting at the segmental level, and by an ipsilateral descending pathway which involves an alpha-adrenoceptor-mediated synapse. Activity in this descending pathway masks the facilitatory effects of opioid antagonists on spinal reflexes in this preparation.

Adrenergic alpha-Antagonists↗