Reducing antibiotic use in children with acute otitis media. Acute otitis media in children is important.
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Acute Disease↗
Biomedical subjects
R W Clarke
Publications and source records attributed to R W Clarke.
Tonic adrenergic and serotonergic inhibition of a withdrawal reflex in rabbits subjected to different levels of surgical preparation.
The excitability of the heel-gastrocnemius withdrawal reflex pathway has been monitored in rabbits undergoing surgical preparation for electrophysiological experimentation under Saffan anaesthesia. Reflexes were evoked by percutaneous electrodes inserted at the heel and recorded as electromyograph signals from the ipsilateral medial gastrocnemius muscle. Two levels of surgery were carried out. The "full surgical" preparation was performed under deep Saffan anaesthesia. The trachea, carotid artery, jugular vein and intrathecal space (via a small laminectomy at L1) were cannulated, the animals were decerebrated by suction, and the left hindlimb was immobilized by screw clamps applied to the tibia and the femur. The sciatic nerve and its branches were exposed by bisection of the posterior biceps muscle and the anaesthetic was withdrawn. In the "reduced surgery" preparation, procedures were carried out with a lighter level of Saffan anaesthesia and operated tissues were infiltrated with local anaesthetic. Only the cannulations were performed in these animals. The excitability of the heel-gastrocnemius reflex declined throughout the full surgical preparation, with the median threshold increasing from 0.8 to 4.2 mA (n=19) and responses to suprathreshold stimuli reducing in size. Most of this effect was reversed after surgery was complete and anaesthesia withdrawn subsequent to decerebration. There were no significant changes in reflex excitability during the reduced surgery preparation (n = 15). Animals prepared by each of these protocols were given increasing intrathecal doses of either the selective alpha2-adrenoceptor antagonist RX 821002 (0.3 to 300 microg) or the serotonin/5-hydroxytryptamine (5-HT)1A-receptor antagonist WAY-100635 (0.01 to 30 microg). Both drugs caused significant, dose-dependent increases in reflex responses, to four to six times pre-drug control in both groups of animals. There were no differences in the effects on reflexes of either drug between the preparations. Thus, surgical preparation of decerebrated rabbits for electrophysiological recording results in depression of hindlimb withdrawal reflexes, although much of this effect did not persist beyond the completion of surgery. Tonic monoaminergic inhibition of reflexes was present to the same extent in both preparations investigated and is not therefore an epiphenomenon of the way in which the animals were prepared.
Adrenergic alpha-Antagonists↗
Spinal section and opioid receptor blockade induce the appearance of Fos-like immunoreactivity in the spinal cord of the decerebrated rabbit.
The expression of Fos-like immunoreactivity has been studied in spinal segments L5-S1 of decerebrated, unanaesthetized, but otherwise unstimulated rabbits. The aim of the study was to establish baseline levels of Fos in such preparations, and to examine how these might change after spinalization and opioid receptor blockade. In animals with an intact spinal cord, approximately 30 Fos-positive profiles per section were found in the superficial dorsal horns (i.e. laminae I and II) of each 40-microm section, while about 20 profiles per section were found immediately adjacent to the central canal (lamina X). Fos-like immunoreactive profiles were rare elsewhere in the gray matter. When the spinal cord was sectioned at L1 (after blockade with local anaesthetic), significantly more Fos-like immunoreactivity was found in superficial and central regions of the gray matter (approximately 90 profiles per section) in animals perfused 4 h after decerebration, but not when perfusion was performed 2 or 8 h after decerebration. The opioid antagonist naloxone (0.25 mg/kg/h) had little effect on expression of Fos-like immunoreactivity in spinalized preparations, but significantly increased the numbers of Fos-positive profiles in all but the ventral areas of the spinal gray matter in non-spinalized preparations. The present data show that spinal section induces a transient increase in expression of Fos in the superficial and central parts of the spinal gray matter. It appears that spinalization induces spontaneous activity in some neurons in these regions of the cord, presumably as a result of relief of descending inhibition. The effects of naloxone indicate that endogenous opioids exert tonic inhibition over Fos-expressing spinal neurons in non-spinalized rabbits.
Animals↗
Differences in opioidergic inhibition of spinal reflexes and Fos expression evoked by mechanical and chemical noxious stimuli in the decerebrated rabbit.
Noxious mechanical and chemical stimuli were applied to the toes of the left hind limb of decerebrated, spinalized rabbits and their effects on a hind limb spinal withdrawal reflex and expression of Fos-like immunoreactivity in the spinal cord were measured. The animals were prepared so as to minimize nociceptive inputs arising from surgery. A single crush stimulus applied with a pair of haemostatic forceps caused long-lasting (c. 20 min) inhibition of reflexes evoked in medial gastrocnemius motoneurons by electrical stimulation of the skin at the heel. Naloxone (0.25 mg/kg i.v.) increased reflexes to more than 1000% of pre-drug controls and reversed crush-evoked inhibition. Mustard oil applied to the toes had no consistent effects on the heel-gastrocnemius reflex before or after naloxone. Both crush and mustard oil stimuli gave rise to unilateral increases in the number of Fos-immunopositive profiles in the superficial dorsal horn of spinal segments L7 and S1. There were significantly more Fos-immunoreactive elements in the central and lateral parts of lamina I of both segments in animals receiving the crush stimulus than there were in animals receiving the mustard oil stimulus. Immunochemical localization of enkephalins in rabbit spinal cord showed a dense network of fibres and terminals in laminae I and II, accompanied by infrequent but distinctly stained neuronal cell bodies. The same pattern, with increased numbers of visible cell bodies, was seen after treatment with colchicine. The present data show that tonic and stimulus-evoked opioidergic inhibition of the heel-gastrocnemius reflex of the rabbit are not epiphenomena of surgical preparation of the hindlimb. Opioid-mediated inhibition of the heel-gastrocnemius withdrawal reflex of the rabbit was evoked by noxious mechanical but not by chemical stimulation of the toes. Of these stimuli, the former gave rise to greater activation of neurons in central and lateral lamina I of segments L7 and S1, the region of termination of afferent fibres from the heel and the location of some enkephalin-positive neuronal cell bodies. Thus, noxious mechanical stimulation of the toes elicits inhibition of the heel-gastrocnemius withdrawal reflex, probably via activation of enkephalinergic neurons in the lateral half of lamina I in the L7 and S1 segments.
Animals↗
Early post-operative morbidity following tonsillectomy in children: implications for day surgery.
Adenotonsillectomy and tonsillectomy are amongst the most commonly performed surgical procedures. In our prospective study we looked at early post-operative morbidity (haemorrhage, vomiting and pyrexia) in 521 consecutive children following tonsillectomy, adenotonsillectomy and adenoidectomy. While the incidence of reactionary haemorrhage is low, pyrexia and vomiting are common. The implications of this high early post-operative morbidity for day surgery are discussed.
Adenoidectomy↗
On the role of 5-HT1B/1D receptors in modulating transmission in a spinal reflex pathway in the decerebrated rabbit.
1. In decerebrated rabbits, the selective 5-HT1B/1D receptor antagonist GR 127,935 had no significant effects on reflexes evoked in medial gastrocnemius motoneurones by electrical stimulation of the sural nerve, or on arterial blood pressure or heart rate when given by the intrathecal (up to 543 nmol cumulative) or intravenous (up to 1.8 micromol cumulative) routes. 2. In decerebrated, spinalized rabbits, intrathecal GR 127,935 in doses of up to 543 nmol, had no effect on the sural-gastrocnemius reflex. Furthermore, this drug failed to alter enhancement of the sural-gastrocnemius reflex induced by 8-hydroxy-2-(di-n-propyl)aminotetralin (8-OH-DPAT), given at 300 nmol kg-1 i.v. 3. In decerebrated, spinalized rabbits, the selective 5-HT1B/1D receptor agonists L-694,247 (cumulative doses of 2 - 243 nmol kg-1 i.v.) and L-741,604 (cumulative doses of 3 - 307 nmol kg-1 i.v.), each caused the sural-gastrocnemius reflex to increase to 140% of pre-drug levels, and arterial blood pressure to rise by about 10 mmHg. Subsequent administration of GR 127,935 at 0.9 - 1.8 micromol kg-1 reversed the pressor effect of the agonists but not the increase in reflexes. The 5-HT1A receptor antagonist WAY-100,635 (185 nmol kg-1 i.v.) also failed to reverse the increase in reflexes, but the 5-HT1B/1D/5-HT2/5-HT7 ligand ritanserin (1.6 micromol kg-1 i.v.) restored reflexes to pre-drug control values after L-741,604 (it was not tested against L-694,247). 4. These data indicate that 5-HT1B/1D receptors do not significantly modulate transmission in the sural-gastrocnemius reflex pathway, and that the enhancement of reflexes by 8-OH-DPAT and L-741,604 is probably mediated by 5-HT7 receptors.
8-Hydroxy-2-(di-n-propylamino)tetralin↗
Urban air particulate inhalation alters pulmonary function and induces pulmonary inflammation in a rodent model of chronic bronchitis.
Epidemiological studies have reported increased morbidity in human populations following inhalation of elevated levels of urban particulate matter. These responses are especially prevalent in populations with chronic obstructive pulmonary diseases, including chronic bronchitis. Toxicological studies have reported altered pulmonary function and increased pulmonary inflammation following particulate inhalation in the laboratory setting. However, most of these studies have utilized artificial particles that may not accurately mimic outdoor air pollutant conditions. Few studies have utilized actual urban air particle samples in inhalation studies. In the present study, the effects of inhaled concentrated urban air particulates on pulmonary function and pulmonary inflammation are addressed. Normal rats and rats with chronic bronchitis induced by approximately 200 ppm SO(2) for 6 wk were subsequently subjected to filtered air or concentrated air particles (CAPs). Twelve rats per group in 4 groups (48 rats total) were exposed for 5 h/day for 3 consecutive days. The CAPs aerosol levels were 206, 733, and 607 microg/m(3) (MMAD = 0.18 microm, sigma(g) = 2.9) on days 1, 2, and 3, respectively. Following the final day of exposure, pulmonary function parameters, including peak expiratory flow (PEF), tidal volume (TV), respiratory frequency (RF), and minute volume (MV), were measured and compared to preexposure baseline levels. Twenty-four hours following the final day of exposure, bronchoalveolar lavage was performed for total cell counts, differential cell counts, and total lavage protein levels. Pulmonary responses to CAPs in chronic bronchitic animals indicated a significant increase in tidal volume as well as peak expiratory flow. In CAPs-exposed animals without underlying bronchitis, significantly increased tidal volume was observed. Significant pulmonary inflammation was observed in the CAPs-exposed animals, particularly those with chronic bronchitis. Significant increases in neutrophils, lymphocytes, and total lavage protein were observed. These results suggest two distinct mechanistic responses to inhaled particles: a stress-type pulmonary function response marked by increases in flow and volume, that is, deeper breathing; and acute pulmonary inflammation marked by cellular influx, particularly neutrophils. From these data it is concluded that inhaled urban air particles alter pulmonary breathing parameters and increase pulmonary inflammation.
Air Pollutants↗
Benchmarking for the competitive marketplace.
One would get little argument these days regarding the importance of performance measurement in the health care industry. The traditional approach has been the straightforward use of measurable units such as financial comparisons and clinical indicators (e.g., length of stay). Also we in the health care industry have traditionally benchmarked our performance and strategies against those most like ourselves. Today's competitive market demands a more customer-focused set of performance measures that go beyond traditional approaches such as customer service. The most important task in today's environment is to study the customers' emerging priorities and adjust our business to meet those priorities.
Ambulatory Care↗
Freshly generated stainless steel welding fume induces greater lung inflammation in rats as compared to aged fume.
It has been previously reported that both short- and long-lived reactive oxygen species (ROS) are present on the surface of freshly generated fumes. The objective of this study was to determine if freshly formed welding fume induces greater lung inflammation and injury in rats due to the presence of reactive oxygen species than aged welding fume. Fume was collected during gas metal arc welding using a stainless steel consumable electrode and found to be of respirable size with a mean diameter of 0.77 microm +/- 0.48. Male CD/VAF rats were dosed intratracheally with the welding fume 30 min (fresh) and 1 and 7 days (aged) after fume collection at a dose of 1.0 mg/100 g b wt. Bronchoalveolar lavage (BAL) was performed 24 h post-instillation. Lung injury and inflammation were assessed by measuring the concentration of neutrophils, albumin, lactate dehydrogenase (LDH), and glucosaminidase (GLU) in the recovered BAL fluid. More neutrophils and enhanced GLU activity were observed for the 'fresh' group as compared to both 'aged' groups (P < 0.05). Slight, but not significant, elevations were seen in albumin content and LDH activity for the 'fresh' group as compared to the 'aged' groups. No significant differences were observed for any of the parameters when fume aged for 1 and 7 days were compared. When the 'fresh' and 'aged' fumes (12.5, 25, and 50 microg/ml) were suspended in dichlorofluorescin (15 microM), a probe which becomes fluorescent when oxidized, the concentration-dependent increases in fluorescence were greater for the 'fresh' fume versus the 'aged' fumes. We have demonstrated that freshly generated stainless steel welding fume induces greater lung inflammation than 'aged' fume. This is likely due to a higher concentration of ROS on fresh fume surfaces.
Air Pollutants, Occupational↗
Opioidergic modulation of spinal reflexes activated by mechanical stimulation of the heel in the decerebrated, spinalized rabbit.
The effects of opioid receptor blockade on reflex responses elicited in medial gastrocnemius and semitendinosus motor nerves by controlled mechanical stimulation of the skin over the heel have been investigated in decerebrated, spinalized rabbits. Pinch forces of 173 mN, 561 mN (light touch), 1642 mN (firm pinch) and 4632 mN (firm to painful) were used. In the control state, background activity was absent from gastrocnemius motoneurones and low in semitendinosus. Pinches of 561 mN and above evoked brisk reflexes in gastrocnemius motoneurones, whereas delayed responses (median latency 1 s) were elicited in semitendinosus by pinches of 1642 mN and 4632 mN. Intravenous administration of the non-selective opioid receptor antagonist (-)-quadazocine (1-781 microg kg(-1)) dose-dependently and stereospecifically increased background activity and enhanced reflex responses to all pinch strengths in both medial gastrocnemius and semitendinosus muscle nerves. Pinches of 173 mN became reflexogenic and higher intensity stimuli evoked significantly larger responses than in the control state. These findings show that tonic opioidergic inhibition in rabbit spinal cord is wide-spread and non-selective, having a powerful influence on transmission of signals to motoneurones from high- and low-threshold cutaneous afferents.
Animals↗
Palatoplasty for snoring: a randomized controlled trial of three surgical methods.
In a randomized, controlled trial, 62 patients (47 men and 15 women) with severe antisocial snoring, but no sleep apnea, were allocated to one of three surgical treatments. These were uvulopalatopharyngoplasty, laser palatoplasty, and diathermy palatoplasty. Postoperative morbidity was measured on a visual analogue scale of severity of pain, dysphagia, and nasal regurgitation at 1, 2, and 7 days after the operation. Efficacy of each procedure was measured by asking the sleeping partner to record the severity of snoring before and after the operation, again on a visual analogue scale. Measurements were taken at 1, 3, and 6 months. There were no significant differences in early postoperative morbidity among the treatment groups. Diathermy palatoplasty is a new technique for the relief of snoring that is associated with low morbidity and requires little in the way of expensive equipment.
Adult↗
Effect of RX 821002 at 5-HT1A-receptors in rabbit spinal cord in vivo.
1. The activity of RX 821002 (2-methoxy idazoxan) at 5-HT1A-receptors in the spinal cord has been investigated in decerebrated, spinalized rabbits. Reflexes evoked in medial gastrocnemius motoneurones by electrical stimulation of the sural nerve were unaffected by intrathecal (i.th.) administration of RX 821002 (111 and 664 nmol cumulative, n = 7), although the highest dose of this drug did produce a significant increase in heart rate of 28 +/- 7 beats min(-1). Subsequent administration of the 5-HT1A-receptor agonist (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) at 300 nmol, i.th., facilitated reflexes to a median of 144% of pre-drug controls, an effect that was partially reversed (to a median value of 120% of pre-drug values) by subsequent administration of the 5-HT1A-receptor antagonist WAY-100635, at 185 nmol i.th. 2. In a separate set of experiments, 8-OH-DPAT was given at 30 nmol i.th. and potentiated reflexes to a median of 170% of pre-drug levels (n = 8). Subsequent administration of RX 821002 (at a cumulative dose of 1.11 micromol, i.th., n = 5) significantly reduced gastrocnemius responses to a median of 154% of control values. 3. After a 3 h recovery period, 8-OH-DPAT was re-administered at 30 nmol, i.th., and increased reflexes to a median value of 151% of pre-drug levels, an effect not significantly different from when it was given alone. WAY-100635 dose-dependently antagonized this effect, causing significant reductions in reflexes at a cumulative dose of 0.55 nmol, i.th., and complete reversal of the effects of 8-OH-DPAT at a cumulative dose of 5.5 nmol. 4. These data show that, at intrathecal doses up to 664 nmol, RX 821002 is devoid of agonist activity at 5-HT1A-receptors. It appears to be a very weak antagonist at these sites in vivo, being some 2000 times less potent than WAY-100635. The inability of WAY-100635 to block completely the effects of high doses of 8-OH-DPAT has been noted previously and can be explained by non-selective actions of the agonist. However, it would appear that a 30 nmol i.th. dose of 8-OH-DPAT is selective for 5-HT1A receptors in this preparation.
8-Hydroxy-2-(di-n-propylamino)tetralin↗
The causes of variations in unit labour costs: a preliminary study.
This paper reports a study of eight National Health Service Trusts, using data drawn from the Unit Labour Costs database and supplementary data collected for the purposes of the study, which set out to begin to explain the large variations in unit labour cost that exist. On the basis of extensive discussions within and between units, it was found that major causes of variations in productivity related to length of stay and bed utilization, which were in turn a result of variations in case mix. Staff utilization was a further major factor. Another observation was that the quality of data, particularly the integration of financial, activity and manpower data, was often poor.
Cost Allocation↗
Oliver St John Gogarty.
Oliver St John Gogarty--Otolaryngologist to fashionable Edwardian Dublin--was a distinguished poet and a Senator in the fledgling Irish Free State after its establishment in 1922. He numbered amongst his acquaintances the poet William Butler Yeats, the novelist James Joyce and a host of political and literary persona who helped to shape modern Ireland. He was satirised as 'stately plump Buck Mulligan' in Joyce's novel Ulysses.
History, 19th Century↗
The surgical treatment of snoring.
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Humans↗
Enhancement and depression of spinal reflexes by 8-hydroxy-2-(di-n-propylamino)tetralin in the decerebrated and spinalized rabbit: involvement of 5-HT1A- and non-5-HT1A-receptors.
1. In decerebrated, spinalized and paralyzed rabbits, intravenous administration of the 5-HT1A-receptor agonists (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 3-300 nmol kg(-1), cumulative) and flesinoxan (22-2200 nmol kg(-1), cumulative) significantly increased the short latency reflex evoked in gastrocnemius medialis motoneurones by electrical stimulation of all myelinated afferents (Abeta and Adelta fibres) of the sural nerve. Reflexes increased to median values of 198% (inter-quartile range (IQR) 148-473%) and 296% (IQR 254-522%) of pre-drug values with the highest doses of 8-OH-DPAT and flesinoxan, respectively. The enhancement of reflexes induced by 5-HT1A-receptor agonists was not reversed by the selective 5-HT1A-receptor antagonist (S)WAY-100135 (2.05 micromol kg[-1]). 2. The effects of 8-OH-DPAT were tested after pretreatment with (S)WAY-100135 (2.05 micromol kg[-1]), its more potent analogue WAY-100635 (185 nmol kg[-1]), and the 5-HT2/5-HT1D-/5-HT7-receptor ligand ritanserin (1.67 micromol kg[-1]). 8-OH-DPAT (300 nmol kg(-1) single dose) significantly increased gastrocnemius reflex responses in the presence of (S)WAY-100135 and WAY-100635, to median values of 260% (IQR 171-295%) and 165% (IQR 136-170%) of pre-drug levels, respectively. These values were not significantly different from each other, or from the effects of 8-OH-DPAT given alone. When 8-OH-DPAT was given after ritanserin, reflexes were a median of 102% (IQR 76-148%) of pre-drug values: i.e. there was no significant increase in responses. Neither WAY-100635 nor ritanserin had any effects on reflexes per se. 3. WAY-100635 (185 nmol kg[-1]) and ritanserin (1.67 micromol kg[-1]) were given after 8-OH-DPAT (300 nmol kg[-1]). The agonist increased reflexes to a median value of 184% (IQR 135-289%), after which WAY-100635 significantly reduced responses to 165% (IQR 130-254%) and ritanserin further decreased reflexes to a median of 107% (IQR 100-154%) of pre-drug levels, i.e. not significantly different from controls. 4. Previous studies have shown that reflexes evoked by large myelinated axons tend to be suppressed, rather than enhanced, by 5-HT1A-receptor agonists. When tested against reflexes evoked by stimulation of the sural nerve at strengths between 1.5 and 2.5 times threshold, 8-OH-DPAT (3-300 nmol kg(-1), cumulative) and flesinoxan (22-2200 nmol kg(-1), cumulative) significantly reduced gastrocnemius responses to median values of 36% (IQR 15-75%) and 17% (IQR 12-38%) of pre-drug levels, respectively. This inhibition was fully reversed by (S)WAY-100135 (2.05 micromol kg[-1]). 5. These data show that drugs that are agonists at 5-HT1A-receptors increase polysynaptic spinal reflexes evoked by moderate to high stimulus intensities and depress responses to very low intensity stimuli. The inhibitory effects of these drugs were mediated through 5-HT1A-receptors as they were abolished by a selective antagonist for these sites. However, the facilitatory effects of 8-OH-DPAT could be completely blocked only by a combination of ritanserin, which has no significant affinity for 5-HT1A-receptors, with WAY-100635. It appears that the enhancement of reflexes by 8-OH-DPAT arises from a combined action at 5-HT1A-receptors and other, ritanserin-sensitive, sites which could be 5-HT1D- or 5-HT7-receptors.
8-Hydroxy-2-(di-n-propylamino)tetralin↗
How we do it: diathermy palatoplasty.
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Adult↗
Characterization of a descending system that enables crossed group II inhibitory reflex pathways in the cat spinal cord.
In the cat, stimulation of group II afferents from hindlimb muscles evokes different crossed reflex actions depending on the integrity of the spinal cord: with the cord intact, extensor motoneurons are inhibited by activation of contralateral group II afferents; after spinal transection, the same stimuli excite these neurons (crossed extension reflex). We have investigated the mechanisms underlying this descending control. To delimit the descending pathway, the effects of funicular lesions of the thoracic cord on the crossed actions on motoneurons were examined. Bilateral lesions of the dorsolateral funiculi abolished the crossed IPSPs as effectively as complete spinal section. If either dorsolateral funiculus was spared, the IPSPs remained. To examine whether serotonergic fibers were involved, the effects of agents selective for 5-hydroxytryptamine (5-HT)1A receptors were examined. After abolishing the crossed IPSPs by spinal transection, systemic administration of the 5-HT1A receptor agonist (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8-OH-DPAT; 0.1-1.3 mg/kg, i.v.) restored the crossed inhibition. This effect was antagonized by the selective 5-HT1A receptor antagonist WAY-100135 (0.7-3.7 mg/kg, i.v.). The simplest explanation of these findings is that a serotonergic pathway, descending via the dorsolateral funiculi and acting via 5-HT1A receptors, is involved: with the spinal cord intact, the pathway would be tonically active and thus enable the crossed inhibition. This raises the possibility that a serotonergic pathway is involved in the selection of specific spinal reflex patterns via 5-HT1A receptors.
Afferent Pathways↗