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Biomedical subjects

R W Clarke

Publications and source records attributed to R W Clarke.

102 records · Page 6Linked to original sources

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↗

The effect of selective electrical stimulation of non-myelinated vagal fibres on heart rate in the rabbit.

The bradycardia evoked by electrical stimulation of the peripheral cut end of the rabbit vagus nerve is mediated by both myelinated and non-myelinated fibres. The purpose of this study was to assess the effects of non-myelinated fibres on heart rate in the rabbit using selective electrical stimulation techniques. In 8 rabbits selective activation of non-myelinated fibres using reversed polarity triangular shaped pulses (10 Hz, 20 s), resulted in a slowly developing fall in heart rate of 24.1 +/- 1.1 beats/min which outlasted the period of stimulation by 58.4 +/- 4.2 s. In 4 rabbits stimulation of myelinated fibres at 10 Hz for 20 s resulted in a fall in heart rate of 24.5 +/- 2.6 beats/min. On stimulation of both myelinated and non-myelinated fibres heart rate fell by 39.9 +/- 3.2 beats/min. Heart rate returned rapidly to control value following stimulation of myelinated fibres (5.6 +/- 0.5 s) but only slowly after stimulation of both myelinated and non-myelinated fibres (56.7 +/- 4.9 s). Atropine (5 mg/kg, i.v.) abolished all effects of vagal stimulation on heart rate. Hexamethonium (15 mg/kg, i.v.) abolished the effect of myelinated fibres on heart rate but did not affect the fall in heart rate produced by non-myelinated fibres. We suggest that the prolonged effects on stimulation of non-myelinated fibres may reflect the persistent action of a non-cholinergic excitatory transmitter at the cardiac parasympathetic ganglia.

Animals↗

The contributions of mu-, delta- and kappa-opioid receptors to the actions of endogenous opioids on spinal reflexes in the rabbit.

Spinal reflexes in the rabbit are suppressed tonically by endogenous opioids. The contributions made to this suppression by mu-, delta- and kappa-opioid receptors have been investigated by studying the actions of a range of opioid antagonists and agonists on reflexes evoked by sural nerve stimulation in the ankle extensor gastrocnemius medialis (g.m.), and in the knee flexor semitendinosus (s.t.). When given at a total dose of 88.5 micrograms kg-1 i.v., either of the universal opioid receptor antagonists (-)-naloxone and (-)-quadazocine enhanced the g.m. response to more than 7 times the pre-drug control values, and the s.t. reflex to 1.5 times controls. The effects of quadazocine were stereospecific. The selective delta antagonist ICI 174864 (3.5 mg kg-1 i.v. total) also augmented the g.m. reflex but only to twice pre-drug controls. The mu-agonists fentanyl (100 micrograms kg-1) and morphine (50 mg kg-1) suppressed both g.m. and s.t. reflex responses to less than half control levels by a naloxone-reversible mechanism. The kappa-agonists bremazocine (50 micrograms kg-1 total), tifluadom (100 micrograms kg-1), ethylketocyclazocine (200 micrograms kg-1) and U50488H (1 mg kg-1) potentiated the g.m. reflex and had variable effects on the s.t. response. Naloxone usually added to the facilitatory actions of these drugs. kappa-Opioid receptor agonists also caused a profound, naloxone-reversible depression of arterial blood pressure. It may be concluded that the endogenous opioid-mediated suppression of spinal reflexes in the rabbit is mediated mainly, if not exclusively, through mu-receptors. There are no known endogenous ligands which are specific for the mu-receptor, so in the present case it seems that selectivity is determined by the receptor population rather than by the ligand.

Animals↗

Streptococci as urinary pathogens.

In a 2-month prospective study of streptococci isolated from urine specimens in the laboratory, 242 strains of catalase-negative gram-positive cocci or coccobacilli were isolated in substantial numbers from 11,725 specimens. These comprised 10% of the important isolates. Species identification of all isolates was undertaken. 74 (30%) of the isolates were of species other than Streptococcus faecalis and S agalactiae. 79 (33%) were not detected on cysteine-lactose-electrolyte-deficient agar after overnight incubation in a carbon dioxide incubator. 20 of the 24 isolates of coccobacilli were Gardnerella vaginalis. Many of the isolates of fastidious species were accompanied by pyuria. An isolation protocol practicable in busy laboratories is proposed.

Adolescent↗

The effects of decerebration and destruction of nucleus raphe magnus, periaqueductal grey matter and brainstem lateral reticular formation on the depression due to surgical trauma of the jaw-opening reflex evoked by tooth-pulp stimulation in the cat.

The effects on the jaw-opening reflex evoked by tooth-pulp stimulation of surgical trauma, decerebration and the destruction of a number of nuclei associated with descending inhibition of trigeminal or spinal neurones have been investigated in the cat. Surgical preparation caused a progressive elevation of the digastric reflex threshold. After decerebration, reflex thresholds remained elevated for 8-11 h before returning to close to pre-surgical control values. Destruction of the nucleus raphe magnus and of the periaqueductal grey matter did not affect the depressed reflex in decerebrate or anaesthetized cats. Variable effects were produced by bilateral ablation of the juxta-raphe reticular formation and destruction of the rostral ipsilateral lateral reticular formation of the brainstem.

Animals↗

The effects of anaesthetics and remote noxious stimuli on the jaw-opening reflex evoked by tooth-pulp stimulation in the cat.

Previous studies indicate that the threshold of the jaw opening reflex (JOR) evoked by tooth-pulp stimulation is much lower in cats subjected to minimal surgical trauma and a short period of anaesthesia than in animals prepared for stereotaxic recording from the brainstem. Experiments have been carried out to determine whether the higher JOR thresholds observed in the latter group of cats could be attributed to the duration of the anaesthesia or the greater surgical trauma to which they were subjected. The effects on the JOR evoked by tooth-pulp stimulation of brief episodes of noxious and high intensity electrical stimulation of other tissues have been studied in anaesthetized cats. In lightly anaesthetized, control animals, the reflex threshold was usually below 100 microA, 0.1 ms and maintained anaesthesia did not affect this. Alphaxalone/alphadolone, methohexitone and alpha-chloralose produced similar results. Noxious or high intensity electrical stimuli applied to a paw, a pinna or the scalp caused either no change or a decrease in the JOR threshold of cats lightly anaesthetized with alphaxalone/alphadolone. With deeper anaesthesia, these same conditioning stimuli caused a maintained increase in JOR threshold which could be reversed by decreasing the anaesthetic dose. The results suggest that the high threshold of the JOR observed in earlier experiments was not due to anaesthesia but may have been caused by trauma.

Anesthetics↗

Post-tetanic depression of spinal reflexes in the rabbit and the possible involvement of opioid peptides.

In spinally transected, decerebrated rabbits, the reflex evoked in the ankle extensor gastrocnemius medialis by stimulation of the ipsilateral sural nerve was depressed for periods of 12-45 min following tetanic stimulation of the high-threshold afferents of the ipsilateral tibial, common peroneal, gastrocnemius medialis and sural nerves. It was unaffected by similar tetanic stimulation of ipsilateral saphenous or semitendinosus nerves, or of any nerve in the contralateral limb. The extension reflex between saphenous nerve and vastus lateralis was depressed after tetanic stimulation of saphenous nerve. Post-tetanic depression was partially reversed by the opioid antagonist (-)-naloxone in a dose of 50 micrograms/kg I.V., implicating the involvement of endogenous opioids. The sural-semitendinosus flexion reflex was depressed only by stimulation of the homonymous muscle nerve. It was enhanced for up to 20 min after iterative stimulation of the high-threshold fibres of the ipsilateral sural nerve. This reflex was unaffected by tetanic stimulation of any of the other ipsilateral or contralateral nerves tested. Tetanic stimulation of high-threshold afferents of hind-limb nerves apparently stimulates the release of endogenous opioids within the spinal cord. It is proposed that this is brought about by the activation of enkephalin-containing neurones in the superficial laminae of the dorsal horn.

Action Potentials↗

Naloxone enhancement of spinal reflexes in the rabbit.

The effects of intravenous morphine, (-)-naloxone and (+)-naloxone have been studied on three ipsilateral cutaneo-muscular reflexes in spinal rabbits. Morphine, 3 mg/kg caused a slow-onset depression of all three reflexes. This effect was naloxone reversible. The ipsilateral extensor reflexes, sural to gastrocnemius medialis and saphenous to vastus lateralis were both enhanced to more than double control size following a 5 micrograms/kg dose of naloxone given in the absence of morphine. For the sural-gastrocnemius reflex, naloxone potentiated the reflex drive from all groups of myelinated afferent fibres. The ipsilateral flexion reflex, sural to semitendinosus, was only weakly enhanced by naloxone, the 5 micrograms dose leading to an increase in the size of the reflex to 130% of control. All observed actions of naloxone were stereospecific as the enantiomer (+)-naloxone failed to affect any of the reflexes even in a dose of 50 micrograms/kg. We conclude from these findings that opioid peptides are tonically released in rabbit spinal cord, and that they have differential effects in control of flexion and extension reflexes. It is suggested that the ipsilateral extension reflexes are held under a more powerful opioid-mediated depression than that operating upon the flexion reflexes, and that this difference may be related to the greater inhibitory inflow to extensor motoneurones from ipsilateral skin areas.

Action Potentials↗

Options for change in the NHS consultant contract.

The lead negotiators for the management and consultant sides in an NHS trust in northern England responded to debate in their trust about consultant contracts by offering to research the attitudes of their peers towards a variety of contract options. The options tested included the current contract; models already examined in the trust and elsewhere, such as time sensitive and mild performance related contracts; and some more radical and speculative possibilities, including consultants franchising their services to the trust. Beyond the predictable conclusion that consultants would prefer no change while managers desired it, a time sensitive contract emerged as having potential for successful negotiation. On the other hand, neither consultants nor managers favoured a strict performance related contract or a fee for service contract. There was a strong similarity of opinion between the two groups on the relative salary values of the options, though the consultants consistently priced these higher than the managers.

Consultants↗

Physicians can benefit from a patient-focused hospital.

To maintain leadership in their markets, a few innovative hospitals, in the late 1980s, developed a revolutionary concept of health care delivery--patient-focused care. Results from pilot projects have shown a considerable increase in patient satisfaction and increased physician productivity. The patient-focused care model boasts faster turnaround times, increased bedside care by caregivers (especially nurses), and an overall increase in the quality of care provided by the staff.

Ancillary Services, Hospital↗