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Biomedical subjects

R W Clarke

Publications and source records attributed to R W Clarke.

At least 73 records · Page 4Linked to original sources
PubMed1996

Inhalation of acid coated carbon black particles impairs alveolar macrophage phagocytosis.

A flow-past nose-only inhalation system was used for the co-exposure of mice to carbon black aerosols (CBA) and sulfur dioxide (SO2) at varying relative humidities (RH). The conversion of SO2 to sulfate (SO4(-2)) on the CBA, at a fixed aerosol concentration, was dependent on RH and SO2 concentration. The effect of the aerosol-gas mixture on alveolar macrophage (AM) phagocytosis was assessed three days following exposure for 4 h. Exposure to 10 mg/m3 CBA alone at low RH (10%) and high RH (85%), to 10 ppm SO2 alone at both RH, and to the mixture at low RH had no effect on AM phagocytosis. In contrast, AM phagocytosis was significantly suppressed following co-exposure at 85% RH, the only circumstance in which significant chemisorption of the gas by the aerosol and oxidation to SO4(-2) occurred. The results suggest that fine carbon particles can be an effective vector for the delivery of toxic amounts of SO4(-2) to the periphery of the lung.

Administration, Inhalation↗
PubMed1996

Spinal 5-HT-receptors and tonic modulation of transmission through a withdrawal reflex pathway in the decerebrated rabbit.

1. In decerebrated, non-spinalized rabbits, intrathecal administration of either of the selective 5-HT1A-receptor antagonists (S)WAY-100135 or WAY-100635 resulted in dose-dependent enhancement of the reflex responses of gastrocnemius motoneurones evoked by electrical stimulation of all myelinated afferents of the sural nerve. The approximate ED50 for WAY-100635 was 0.9 nmol and that for (S)WAY-100135 13 nmol. Intrathecal doses of the antagonists which caused maximal facilitation of reflexes in non-spinalized rabbits had no effect in spinalized preparations. 2. In non-spinalized animals, intravenous administration of (S)WAY-100135 was significantly less effective in enhancing reflexes than when it was given by the intrathecal route. 3. When given intrathecally, the selective 5-HT 2A/2C-receptor antagonist, ICI 170,809, produced a bellshaped dose-effect curve, augmenting reflexes at low doses (< or = 44 nmol), but reducing them at higher doses (982 nmol). Idazoxan, the selective alpha 2-adrenoceptor antagonist, was less effective in enhancing reflex responses when given intrathecally after ICI 170,809 compared to when it was given alone. Intravenous ICI 170,809 resulted only in enhancement of reflexes and the facilitatory effects of subsequent intrathecal administration of idazoxan were not compromised. 4. The selective 5-HT3-receptor blocker ondansetron faciliated gastrocnemius medialis reflex responses in a dose-related manner when given by either intrathecal or intravenous routes. This drug was slightly more potent when given i.v. and it did not alter the efficacy of subsequent intrathecal administration of idazoxan. 5. None of the antagonists had any consistent effects on arterial blood pressure or heart rate. 6. These data are consistent with the idea that, in the decrebrated rabbit, 5-HT released from descending axons has multiple roles in controlling transmission through the sural-gastrocnemius medialis reflex pathway. Thus, it appears 5-HT tonically inhibits transmission between sural nerve afferents and gastrocnemius motoneurones by an action at spinal 5-HT1A-receptors. Spinal 5-HT2A/2C-receptors may mediate a weak inhibition of transmission in the spinal cord, but more convincing evidence was obtained for their involvement in descending facilitatory tone. Further, some of the facilitatory consequences of spinal alpha 2-adrenoceptor blockade may be mediated through 5-HT2 type receptors. Spinal 5-HT3 receptors do not appear to have a major role in tonic modulation of the sural-gastrocnemius medialis reflex.

Animals↗
PubMed1995

NK1-tachykinin receptors and prolonged, stimulus-evoked alterations in the excitability of withdrawal reflexes in the decerebrated and spinalized rabbit.

Intense natural or electrical stimulation of afferents from the toes or the heel results in prolonged changes in the excitability of the heel withdrawal reflex pathway in the rabbit. This study has investigated the roles played by tachykinin NK1 receptors in mediating these effects. Reflexes were evoked by electrical stimulation of the sural nerve and recorded from the gastrocnemius medialis muscle nerve. High-intensity electrical stimulation of the common peroneal nerve, or application of a crush stimulus to the toes, resulted in suppression of gastrocnemius reflex responses to between 30 and 50% of controls, from which recovery was complete in 15-25 min. In contrast, intense electrical stimulation of the sural nerve, or application of mustard oil to the heel, facilitated the sural to gastrocnemius reflex to two to four times control values. Recovery was rarely complete within 30 min of these stimuli. Administration of the NK1 receptor antagonist CP-96,345, but not its enantiomer CP-96,344, reduced gastrocnemius reflex responses to sural nerve stimulation per se; significantly decreased the time to recovery after common peroneal nerve stimulation and toe crush (but did not affect maximum inhibition); and significantly reduced the facilitation of reflexes resulting from sural nerve stimulation or mustard oil applied to the heel in the first 3-5 min after the application of the stimuli. Both CP-96,345 and CP-96,344 reduced blood pressure and heart rate. These data show that: (i) blockade of NK1-receptors reduces excitatory drive from sural nerve afferents to GM motoneurones; (ii) NK1-receptors are involved in the generation of the early excitatory events which follow stimulation of nociceptive afferents from the heel; and (iii) have a role in the later stages of prolonged, opioid-mediated inhibition of reflexes resulting from activation of fine afferents from the toes. We believe that (ii) and (iii) reflect a role for tachykinins as transmitters from small diameter primary afferent fibres.

Afferent Pathways↗
PubMed1995

Tachykininergic tone in the spinal cord of the rabbit: dependence on nociceptive input arising from invasive surgery.

In the decerebrated and spinalized rabbit, reflexes evoked in the gastrocnemius medialis muscle nerve by electrical stimulation of teh sural nerve are suppressed after blockade of NK-tachykinin receptors. This observation suggests that endogenous tachykinins tonically enhance transmission between sural nerve afferents and gastrocnemius motoneurons. In the present study we have investigated some possible sources of this tachykininergic tone. Electrical stimulation of the sural nerve at 1 Hz, as used in our previous investigation, leads to increased gastrocnemius reflex responses with successive stimuli. We examined reflexes evoked by pairs of sural stimuli separated by intervals of 10-1000 ms, and found that responses to the second stimuli of such pairs were significantly enhanced at intervals from 50 to 500 ms. Treatment with the NK receptor antagonist CP-99,994 [(+)-(2S,3S)-3-(2-methoxybenzylamino)-2-phenylpiperidine; 1 mg/kg, i.v.] reduced gastrocnemius reflex responses per se, but did not alter the facilitatory effects of pairing sural stimuli. Subsequent treatment with the glutamate N-methyl-D-aspartate receptor blocker dizocilpine (0.5 mg/kg, i.v.) further reduced reflex responses and abolished paired-pulse facilitation. In a second set of experiments, rabbits were prepared so that reflexes could be studied with minimal surgical preparation of the hindlimb. Reflex responses recorded in this way were enhanced by treatment with CP-99,994 (up to 1 mg/kg, i.v.). Subsequent administration of the opioid receptor antagonist naloxone (1-10 microg/kg, i.v.) increased reflexes, as seen previously in surgically-prepared animals. These data show that tachkininergic modulation of spinal reflexes in the rabbit results from the nociceptive input arising from surgical preparation of the leg. In contrast, tonic opioidergic inhibition of reflexes is not substantially dependent on such input.

Animals↗
PubMed1995

Peak nasal inspiratory flow--the plateau effect.

To study the efficacy of peak nasal inspiration flow (PNIF) as a means of recording change in nasal patency 20 subjects were given increasing doses of intranasal xylometazoline. Nasal resistance (NR) and peak nasal inspiratory flow (PNIF) were measured in the resting state and after each xylometazoline administration. Successive increases in dose caused a progressive decrease in nasal resistance and an increase in PNIF but the change in peak nasal inspiratory flow (PNIF) was much less. Peak nasal inspiratory flow shows a plateau effect as nasal resistance decreases. The reasons for this plateau are discussed in terms of respiratory flow mechanics.

Adult↗
PubMed1995

The effect of nasal mucosal vasoconstriction on nasal airflow sensation.

The correlation between the objective measurement of nasal resistance and nasal airflow sensation is usually regarded as poor. To investigate the relationship between these two parameters 20 healthy volunteers had nasal resistance to airflow measured by rhinomanometry compared with nasal sensation by visual analogue scoring before and after nasal mucosal vasoconstriction using topical 0.1% xylometazoline. The median change in nasal resistance was 0.2 kPal-1s (95% CI 0.08-0.28 kPal-1s) and in nasal sensation 24 mm (95% CI 17 mm-35 mm). A significant relationship between nasal sensation and nasal resistance to airflow was found (Kendall's Rank correlation (P < 0.05). This function can be described by the linear regression equation: dS = 13.2 + 70.dNR where dS = change in nasal sensation and dNR = change in nasal resistance. There may be a much closer relationship between subjective and objective measures of nasal patency than has previously been thought.

Adult↗
PubMed1994

Identification of nocifensor reflex-related neurons in the rostroventromedial medulla of decerebrated rats.

Extracellular single unit recordings were made from neurons in the rostroventromedial medulla of decerebrated rats. The previously described 'on-cell' and 'off-cell' classes were found in this preparation, and this classification, which is based on tail flick-related changes in activity, was not altered by the introduction or removal of halothane anesthesia. It is therefore evident that the identifying physiological properties of on- and off-cells are not dependent on the presence of anesthesia in decerebrate rats, or on brain structures rostral to the inferior colliculi.

Anesthesia↗
PubMed1994

Novel methods for the preparation of antibody microprobes.

Antibody microprobes are devices which have been used to determine the release sites of several neuropeptides. The production of microprobes using the previous methodology is a time-consuming procedure requiring a high level of skill. The aim of the study was to investigate alternative methods for the production of microprobes which would simplify this procedure. Specific antibodies to thyrotrophin-releasing hormone (TRH) were bound to the outside of glass and tungsten wire microprobes using (a) an aminosilane coating, (b) a polycarbonate plastic coating and (c) an epoxylite resin-activated charcoal coating. Microprobes were assessed in vitro and in vivo for their ability to measure the neuropeptide TRH. All methods considerably reduced the time required to manufacture microprobes (more than 5-fold) and the aminosilane and epoxylite resin/charcoal-coated probes were suitable for use in vivo. The preferred binding coat was epoxylite/charcoal which has now been used to determine sites of TRH release in rat brain.

Animals↗
PubMed1994

The distribution of nasal airflow sensitivity in normal subjects.

Nasal airflow modifies the pattern of ventilation presumably due in part to nervous signals arising in the nose and transmitted along the trigeminal nerve to the respiratory centre. Nasal receptor tissue must also be important in determining the sensation of airflow at a conscious level but little attention has been paid to the distribution and function of these receptors. An experimental model to deliver a pulse of air at different velocities to various nasal test sites is described. In this way nasal sensitivity to an air jet can be mapped out. Sensitivity of the nose to an air jet is greatest at the entrance to the nose--the region of the nasal vestibule.

Adult↗
PubMed1994

Vocal rehabilitation after pharyngo-laryngectomy--the Provox valve.

We describe our experience using the Provox voice prosthesis in patients undergoing free jejunal loop transfer following total pharyngo-laryngectomy. From our series and the few reports in the literature, the use of a voice prosthesis appears to be an effective method of speech rehabilitation in this group of patients.

Aged↗
PubMed1994

The limitations of peak nasal flow measurement.

The Youlten Peak Nasal Flow Meter is a convenient device for obtaining objective measurments of nasal patency and gives static values which correlate well--though inversely--with resistance measured by rhinomanometry. In this study peak nasal flow and nasal resistance are compared before and after intranasal challenge using histamine. The comparatively small change in nasal resistance induced by low-dose histamine is not reliably detected by the peak flow meter. Large changes in nasal resistance with a higher dose of histamine are reflected by significant but small changes in peak nasal inspiratory flow. It is concluded that changes in nasal patency as measured by the Youlten meter are an insensitive measure of nasal patency compared with rhinomanometrically measured resistance changes. Continued use of the latter is recommended for physiological research.

Administration, Intranasal↗
PubMed1993

Motor and cardiovascular effects of selective alpha 2-adrenoceptor antagonists in the decerebrated rabbit.

In the decerebrated rabbit, intrathecal administration of the alpha 2-adrenoceptor antagonists idazoxan and yohimbine increases reflex responses of gastrocnemius motoneurones to electrical stimulation of the sural nerve. The maximum effect of idazoxan is about twice that of yohimbine, suggesting that part of the effect of idazoxan may be due to an action at non-adrenergic idazoxan or imidazoline binding sites. RX811059 and RX821002 are selective alpha 2-adrenoceptor antagonists with minimal affinity for imidazoline binding sites. In the present study it was found that intrathecal administration of these compounds in doses of 5-200 micrograms increased the sural-gastrocnemius reflex to the same level as idazoxan, confirming that this reflex is subject to powerful adrenergic inhibition mediated through spinal alpha 2-adrenoceptors. RX811059 and RX821002 also increased arterial blood pressure and heart rate. A retrospective analysis of data from earlier studies showed that whereas intrathecal yohimbine had increased blood pressure, idazoxan had not. It is possible that idazoxan acts at non-adrenergic idazoxan binding sites to cancel out the hypertensive effects which are associated with alpha 2-adrenoceptor blockade.

Adrenergic alpha-Antagonists↗
PubMed1993

Detection of thyrotrophin releasing hormone in rat brain in vivo using novel antibody microprobes: effects of amphetamine.

Antibody microprobes of novel design were used to monitor thyrotrophin releasing hormone (TRH) in rat brain before and after-parenteral administration of amphetamine. Specific antibodies to TRH were bound to the outside of glass microprobes by adsorption to a surface of activated charcoal embedded in epoxylite resin. In male Wistar rats anaesthetised with chloral hydrate a series of antibody microprobes were implanted in forebrain. Amphetamine (10 mg/kg i.p.) caused a highly significant decrease in the binding of 125I-TRH to microprobes, indicating an increase in extracellular TRH localised in the lateral septum. There was also evidence of TRH release in the septo-hypothalamic nucleus. Neither saline, nor amphetamine at 2 mg/kg were able to evoke changes in the release of TRH at any sites.

Amphetamine↗
PubMed1993

Recurrent pleomorphic adenoma.

Of 209 cases of pleomorphic adenoma treated in a 30 year period, 38 were secondary referrals with recurrent disease following surgery. Of these, 25 were women and 13 men with a mean time to recurrence of 9 years 4 months. Thirty-four recurrences were in the parotid gland, three in the submandibular gland and one in the anterior faucial pillar. Seven patients were untreated due to poor general condition or refusal of further treatment. Of the remainder, 15 had superficial parotidectomy and excision of the scar and nine a total parotidectomy. Three of these had extensive surgery with local flap repair. Of the patients with submandibular gland recurrence, two had local excision and one was treated with radiotherapy alone. One patient had a recurrence in the faucial pillar. Three patients developed malignant change in the recurrent tumour, of whom one died of disease.

Adenoma, Pleomorphic↗
PubMed1993

The effect of histamine challenge on nasal airflow sensation.

Objective nasal airflow resistance, as measured by the rhinomanometer, and the subjective sensation of nasal patency are usually regarded as showing poor correlation. However, previous population studies comparing nasal resistance and subjective nasal airflow sensation have failed to take into account the great individual variation in resting nasal resistance. To investigate the potential relationship between the two parameters, 20 healthy volunteers underwent histamine nasal challenge tests. Nasal resistance prior to the intra-nasal administration of histamine ('resting' nasal resistance, NRR) was compared with nasal resistance when the subject reported a subjective sensation of nasal blockage ('obstructed' nasal resistance, NR0) and the two were found to be significantly correlated using the Spearman rank correlation method (rs = 0.648, P = 0.002). Linear regression analysis using the method of least squares demonstrated an association between the two variables (P = 0.029), conforming to the formula NR0 = 1.26NR+0.478, (resistance units kPa.s.l-1). Subjective and objective measurements of nasal patency may be much more closely related than has previously been reported.

Administration, Intranasal↗
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↗