Consultant to the pharmaceutical industry on clinical trials and treatments for cough, colds and flu
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Papers by Ronald Eccles
A Study of the Synthesis and Inactivation of Prostaglandin E by Pig Nasal Mucosa
Acta Oto-laryngologica, 1984
Prostaglandins of the E series have been shown to be more potent than adrenaline as nasal deconge... more Prostaglandins of the E series have been shown to be more potent than adrenaline as nasal decongestants. We now present evidence that prostaglandins of the E series (PGE) can be synthesised and inactivated by the nasal mucosa of the pig. This study demonstrates that PGE may be formed by pieces of pig nasal mucosa in vitro and that PGE formation by the nasal mucosa is inhibited by indomethacin. The nasal mucosa was also shown to contain 15-hydroxy prostaglandin dehydrogenase activity and this enzyme is involved in the inactivation of PGE. The findings of this study may help towards a better understanding of the role of PGE in nasal physiology and nasal disease.
Objective evidence for the efficacy of surgical management of the deviated septum as a treatment for chronic nasal obstruction: a systematic review
Clinical Otolaryngology, Apr 1, 2011
Nasal septal surgery is a common procedure, but there are concerns that the benefits of this surg... more Nasal septal surgery is a common procedure, but there are concerns that the benefits of this surgery are mainly cosmetic. The primary aim is to identify any functional benefits of septal surgery and provide any evidence of a change in patency of the nasal airway, as assessed by objective methods such as rhinomanometry, acoustic rhinometry and peak nasal inspiratory flow. Systematic review. A systematic search of the available literature was performed, using Pubmed, Medline (1950-November 2010), Embase (1947-November 2010) and the Cochrane Controlled Trials Register. Papers written in English that objectively compared pre- and post-surgical treatment of nasal obstruction in adults because of septal deviation were reviewed. Objective measurements of rhinomanometry, acoustic rhinometry and nasal peak inspiratory flow were specified within the search. Searches were restricted to surgery on the nasal septum, which included septoplasty, submucous resection and septal (deviation) corrective surgery. Seven studies (460 participants) involving rhinomanometry, six studies (182 participants) with acoustic rhinometry and one study (22 participants) using nasal peak inspiratory flow were included in the review. All the studies reported an objective improvement in nasal patency after septal surgery. Mean unilateral nasal resistance (data from six studies) decreased from preoperative 1.19 Pa/cm(3) /s to postoperative 0.39 Pa/cm(3) /s, mean minimum cross-sectional area (data from five studies) increased from preoperative 0.45 cm(2) to postoperative 0.61 cm(2) , median peak nasal inspiratory flow (data from one study) increased by 35 L/min after surgery. There is sufficient evidence in the literature to conclude that septal surgery improves objective measures of nasal patency and that improved nasal airflow may have beneficial effects for the patient.
Spontaneous Changes of Unilateral Nasal Airflow in Man. A Re-examination of the ‘Nasal Cycle’
Acta Oto-laryngologica, 1997
It is now over 100 years since Kayser (Archiv für Laryngol Rhinol 1895; 3: 101-120) first reporte... more It is now over 100 years since Kayser (Archiv für Laryngol Rhinol 1895; 3: 101-120) first reported in the scientific literature that the human nasal passages exhibit spontaneous changes in unilateral nasal airway resistance, yet our understanding of this unusual phenomenon is still very confused. Spontaneous, reciprocal changes in unilateral nasal resistance are often referred to as a "nasal cycle" and although this term is now commonly used to describe spontaneous changes in nasal resistance in man and animals, there is little evidence for any true periodicity. A major problem in increasing our knowledge and understanding of the so-called "nasal cycle" is that most studies have relied on simple descriptions of the changes in nasal resistance and have not developed any numerical parameters to quantify the changes in resistance over time. This lack of definition of what actually constitutes a nasal cycle has meant that the literature of the present day generally accepts the views put forward by Heetderks (Am J Med Sci 1927; 174; 231-244) and Stoksted (Acta Otolaryngol (Stockh) 1953; Suppl 109: 159-175) that around 80% of the healthy population exhibit a regular cycle. In order to define the characteristics of the spontaneous changes in nasal airway resistance we have used numerical measures of reciprocity and also developed a measurement of the division of airflow between the nasal passages over time. With these two parameters it is possible to describe the nature of the spontaneous changes in airflow in numerical terms and to define what exactly constitutes a nasal cycle. Fifty-two volunteers underwent hourly measurement of unilateral nasal airflow for 8 h. For each volunteer, two values were derived from the graph of unilateral nasal airflows against time; the correlation coefficient between unilateral airflows (r) and the airflow distribution ratio between the two nasal airways (ADR). The spread of different types of airflow pattern (nasal cycle) throughout the population was illustrated by plotting r against ADR for each subject. A nasal cycle was defined as having an r value between -0.6 and -1.0, and an ADR value between 0.7 and 1.0. Only 21% (11 of the 52 volunteers) exhibited airflow patterns that could be defined as a nasal cycle in these terms. This finding contradicts the generally accepted, but undefined, view that around 80% of the population exhibit a regular nasal cycle. The numerical definition of a nasal cycle in terms of both reciprocity and airflow distribution, as described in this paper may help to clarify our understanding of this interesting phenomenon and allow rhinologists to describe the spontaneous changes in nasal airflow in more exact terms than have been used previously in the literature.
Lack of effect of codeine in the treatment of cough associated with acute upper respiratory tract infection
Journal of Clinical Pharmacy and Therapeutics, Jun 1, 1992
Codeine is often used as a standard antitussive against which new antitussives are compared. Howe... more Codeine is often used as a standard antitussive against which new antitussives are compared. However there is little information available about the effects of codeine on cough associated with upper respiratory tract infection. The present study investigated the effects of codeine syrup B.P. (30 mg/10 ml, q.d.s.) or syrup vehicle on cough frequency and the subjective severity of cough during a 3-h laboratory phase and a 4-day home phase of treatment. Cough frequency and subjective scores of cough severity were significantly decreased during the 3-h laboratory phase but at no time point was there a significant difference between the codeine- and placebo-treated groups. The results of the 4-day home phase diary were similar to those of the laboratory phase as at no time point was there a significant difference between the mean scores for the codeine- and placebo-treated groups. The results indicate that codeine, either as a single 30-mg dose or in a total daily dose of 120 mg, is no more effective than the syrup vehicle in controlling cough associated with acute upper respiratory tract infection.
Role of cold receptors and menthol in thirst, the drive to breathe and arousal
Appetite, Feb 1, 2000
Menthol is widely used in candy, chewing gum, toothpastes, cigarettes and common cold medications... more Menthol is widely used in candy, chewing gum, toothpastes, cigarettes and common cold medications. Menthol has been shown to stimulate cold receptors in the mouth and nose. The present paper puts forward the hypothesis that menthol, by its effects on oral and nasal cold receptors, may influence thirst, the drive to breathe, and arousal. The satisfying effects of menthol on thirst and breathing, together with an effect on arousal, may explain the popularity of menthol and account for the very large amount of menthol-containing products that are consumed each day.
Changes in Human Nasal Resistance Associated With Exercise, Hyperventilation and Rebreathing
Acta Oto-laryngologica, 1977
The nasal resistance to airflow determined in four subjects for periods of up to 7 hr. Cyclic cha... more The nasal resistance to airflow determined in four subjects for periods of up to 7 hr. Cyclic changes in the resistance of each nasal passage were demonstrated in 13 or 24 experiments. After exercise on the cycle ergometer the total nasal resistance decreased and this change in nasal resistance was found to be directly related to the work rate. After oral rebreathing, the total nasal resistance decreased, and after hyperventilation the total nasal resistance increased. These changes in resistance are believed to be caused by changes in arterial pCO2 and mediated by the autonomic innervation of the nasal vasculature.
This review examines our present understanding of the physiology, pathophysiology and pharmacolog... more This review examines our present understanding of the physiology, pathophysiology and pharmacology of nasal airflow. The main aim of the review is to discuss the basic scientific and clinical knowledge that is essential for a proper understanding of the usefulness of measurements of nasal airflow in the clinical practice of rhinology. The review concludes with a discussion of the measurement of nasal airflow to assess the efficacy of surgery in the treatment of nasal obstruction. Areas covered by the review include: influence of nasal blood vessels on nasal airflow; nasal valve and control of nasal airflow; autonomic control of nasal airflow; normal nasal airflow; nasal cycle; central control of nasal airflow; effect of changes in posture on nasal airflow; effect of exercise on nasal airflow; effect of hyperventilation and rebreathing on nasal airflow; nasal airflow in animals; cerebral effects of nasal airflow; sensation of nasal airflow; sympathomimetics and sympatholytics; histamine and antihistamines; bradykinin; and corticosteroids.
THE INFLUENCE OF AN EXTRANEURONAL COMPARTMENT ON THE RELAXATION OF THE CAT NICTITATING MEMBRANE in vivo
British Journal of Pharmacology, Apr 1, 1978
Contractions of the cat nictitating membrane were elicited on stimulation of the internal carotid... more Contractions of the cat nictitating membrane were elicited on stimulation of the internal carotid nerve, and the effects were studied of desipramine and two inhibitors of catechol‐O‐methyltransferase, U‐0521 and pyrogallol, on the subsequent relaxation of the muscle. The relaxation of the nictitating membrane occurred in at least two phases. The late phase of relaxation was prolonged after increase in the period of nerve stimulation and the duration of this phase was further prolonged after treatment with pyrogallol. After inhibition of neuronal uptake of noradrenaline with desipramine both the early and late phases of relaxation were increased in duration, and subsequent administration of pyrogallol or U‐0521 caused a further increase in the duration of the late phase of relaxation. The results suggest that the late phase of relaxation of the nictitating membrane is influenced by efflux of noradrenaline from an extraneuronal pool.
The isolation of prostaglandin E from pig nasal mucosa
Clinical Otolaryngology, Jun 1, 1983
Prostaglandins of the E series (PGE) have been shown to be potent nasal vasoconstrictors but have... more Prostaglandins of the E series (PGE) have been shown to be potent nasal vasoconstrictors but have not previously been isolated from the nasal mucosa. Here we report the isolation of a biologically active substance with properties similar to PGE from pig nasal mucosa. The substance was identified as PGE on the following criteria: 1 our isolation procedure demonstrated the presence of a biologically active polar acidic lipid; 2 caused contractions of the isolated rat stomach fundic strip similar to PGE2; 3 caused a prolonged nasal vasoconstriction similar to PGE2; 4 travelled on thin layer chromatogram with PGE. The PGE found in the nasal mucosa may have a role in the regulation of mucosal blood flow in normal and pathological conditions.
1. The effects of nasal stimulation using an air jet or balloon on the electro- myographic (e.m.g... more 1. The effects of nasal stimulation using an air jet or balloon on the electro- myographic (e.m.g.) activity ofa nasal muscle, the levator labii superioris alaeque nasi component of the quadratus labii superioris muscle, were studied in the anaesthetized cat. 2. Respiratory related nasal e.m.g. activity was recorded and this normally con- sisted of two components, one coinciding with the onset of inspiratory airflow and a larger component which commenced at the onset of expiratory airflow and often persisted until the onset of the following inspiratory airflow. 3. An air jet (room air, 1-8 1/min, temperature 24 °C) applied to the nasal vestibule by means of a small nozzle caused an increase in the amplitude of the ipsilateral spontaneous nasal e.m.g. activity. 4. The increase in nasal e.m.g. activity caused by the nasal air jet was unaffected by warming the airflow from 30 to 40 'C. 5. A sustained increase in nasal e.m.g. activity was caused by application of pressure to the walls of the nasal vestibule by means of a small balloon. 6. Section of the ethmoidal and infra-orbital branches of the trigeminal nerve abolished the increase in nasal e.m.g. amplitude caused by nasal stimulation with the air jet, whilst section of the facial nerve abolished the spontaneous respiratory nasal e.m.g. activity. 7. The results indicate that there are sensory receptors in the nasal vestibule which respond to nasal positive pressure and cause a reflex increase in nasal e.m.g. activity.
Characteristics of the sympathetic innervation of the nictitating membrane and of the vasculature of the nose and tongue of the cat
Journal of Neural Transmission, Mar 1, 1976
Vasomotor responses from the nasal mucosa and tongue, and contractions of the nictitating membran... more Vasomotor responses from the nasal mucosa and tongue, and contractions of the nictitating membrane, were recorded on stimulation of the cervical sympathetic or internal carotid nerves. Preganglionic sympathetic nerve fibres which elicited a membrane response possessed a lower threshold than those which evoked nasal vasoconstriction, while the latter displayed a lower threshold than fibres which evoked tongue vasoconstriction. The sympathetic vasodilator fibres to the tongue whose activity was revealed after alpha-receptor blockade, had a similar threshold to the vasoconstrictor fibres. Membrane contraction, nasal vasoconstriction and occasionally tongue vasoconstriction could be evoked by stimulating the internal carotid nerve. The postganglionic fibres innervating the nasal mucosa had a similar threshold to those of the nictitating membrane, which may indicate that there are small myelinated fibres innervating the mucosa. The preganglionic compound nerve action potential had four major components, S1-S4. S1, S2 and usually S3 fibres were associated with membrane contraction; S2, S3 and sometimes S1 fibres were associated with nasal vasoconstriction; and S3, usually S2 and occasionally S1 fibres were associated with vasoconstriction in the tongue. It is concluded that each of these three groups of nerve fibres, but not S4 fibres, may include fibres associated functionally with the three effectors. There was a considerable difference between the relative amplitude of the responses of the three effectors elicited by stimulation of the cervical sympathetic nerve at frequencies between 0.2 and 2 Hz. Vasoconstrictor responses were relatively larger than membrane contractions suggesting differences in the mechanisms of neurotransmission at the neuroeffector junctions.
A method for studying in vivo the process of neuroeffector transmission in the nictitating membra... more A method for studying in vivo the process of neuroeffector transmission in the nictitating membrane and nasal blood vessels of the cat is described. 2 Administration of desmethylimipramine or cocaine caused increases in both the amplitude and duration of the nasal and membrane responses which may be explained by inhibition of neuronal uptake of noradrenaline. 3 Phenoxybenzamine depressed the responses to nerve stimulation, but had little effect on the relationship between response amplitude and rate of recovery. 4 The relationship between response amplitude and rate of recovery is discussed and related to the sigmoid shape of a log concentration-response curve.
It is the familiar symptoms of sore throat, runny nose, sneezing, and nasal congestion, muscle ac... more It is the familiar symptoms of sore throat, runny nose, sneezing, and nasal congestion, muscle aches, chilliness and fever, etc., that define the common cold and flu syndromes as self-diagnosed illnesses. Although there is much information about the molecular biology of the viruses that cause the common cold and flu syndromes, there is relatively little research on the immunological, physiological and pathophysiological mechanisms involved in generating the symptoms. This chapter studies the mechanisms that cause local symptoms associated with local inflammation of the airway (sore throat, sneezing, rhinorrhoea and purulent nasal discharge, nasal congestion, sinus pain, watery eyes and cough), and the mechanisms that cause systemic symptoms associated with release of cytokines from leukocytes (headache, chilliness and fever, psychological effects, malaise and mood changes, loss of appetite, and muscle aches and pains).
Data from north west England support Oxfordshire findings Editor-Wyllie et al conclude that admis... more Data from north west England support Oxfordshire findings Editor-Wyllie et al conclude that admission cultures accounted for 24% of total hospital methicillin resistant Staphylococcus aureus (MRSA) bacteraemia episodes over seven years to March 2004. 1 Data collected from five district general hospitals and one university hospital in Cheshire and Merseyside and one district general hospital in greater Manchester support this view. This group of hospitals has collected enhanced MRSA bacteraemia surveillance data using published case definitions from the Department of Health since April 2004. Anonymised data are collected on paper forms and analysed using the FORMIC data capture system. In all, 534 cases of S aureus bacteraemia were identified between April 2004 and March 2005, 334 being methicillin sensitive S aureus bacteraemia and 200 MRSA bacteraemia. Sixty six of the MRSA bacteraemia cases occurred within 48 hours of arrival in hospital, 16 being related to a previous hospital admission, 25 in patients known to have been colonised with MRSA, and 13 in patients admitted from nursing or residential homes. Thirty five cases were admitted as medical specialties, 25 of them in patients over 65. Our results support the suggestion by Wyllie et al that anti-MRSA treatment should be considered for patients with possible staphylococcal sepsis who have previously been admitted or known to be colonised with MRSA. In a predominantly district general hospital setting, anti-MRSA treatment should also be considered for possible staphylococcal sepsis in elderly medical admissions and admissions from nursing homes.
The treatment and management of acute cough due to common cold costs billions of dollars of healt... more The treatment and management of acute cough due to common cold costs billions of dollars of healthcare expenditure and there is a growing opinion that a simple linctus containing glycerol with flavourings such as honey and lemon is a safe and effective treatment for acute cough in children and adults. Glycerol is a component of most cough syrups, and although it is often thought of only as a solvent or thickening agent in cough syrups, it may be a major component for the efficacy of cough syrups due to its special properties of lubrication, demulcency, sweetness, and acting as a humectant. The major benefit of cough syrups in soothing cough is likely due to the properties of the syrup rather than the active ingredients and this review discusses the special properties of glycerol in relation to the treatment of acute cough.
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Papers by Ronald Eccles