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Biomedical subjects

R Eccles

Publications and source records attributed to R Eccles.

At least 55 records · Page 3Linked to original sources

Changes in the amplitude of the nasal cycle associated with symptoms of acute upper respiratory tract infection.

Nasal airflow is normally asymmetrical and subject to spontaneous reciprocal changes which are often referred to as the 'nasal cycle'. The nature of these spontaneous changes in nasal resistance is poorly understood and little information is available about how they are affected by nasal disease. In order to understand the changes in nasal resistance in health and disease it is important to record unilateral resistance rather than express results as total nasal resistance. Unilateral resistance is subject to continuous reciprocal changes and therefore new measurements were developed in this study in order to quantify the nasal resistance of each nasal passage. Twelve human subjects (age 19-38) with symptoms of acute respiratory tract infection (URTI) were recruited for the study which involved serial measurements of unilateral nasal airway resistance using the technique of posterior rhinomanometry over a period of six hours. Measurements were made on one day when subjects had symptoms of URTI and then repeated 6-8 weeks later when subjects were healthy. The results of this study show that all of the subjects exhibited spontaneous reciprocal changes in nasal airway resistance on both study days but that there was a significant increase in the amplitude of the changes in resistance when the subjects had symptoms of URTI with one nasal passage often becoming severely congested. In order to quantify the amplitude of the reciprocal changes in nasal resistance two new measures were used. The minimum and maximum nasal airway resistance recorded for each nasal passage during the six hour recording period (MIN NAR and MAX NAR). Mean MIN NAR with URTI was 0.4 Pa cm3s +/- 0.07 which was not significantly different from mean MIN NAR in health which was 0.36 Pa cm3s +/- 0.05 (p = 0.22, n = 20). The mean MAX NAR during URTI was 2.44 Pa cm3s +/- 0.38 and this decreased significantly to 1.36 +/- 0.17 when recorded during healthy conditions (p = 0.01, n = 20). The increased amplitude of spontaneous reciprocal changes in nasal airway resistance associated with symptoms of URTI is proposed to be due to an increased filling pressure to the nasal venous sinusoids associated with a nasal inflammatory response. A model is proposed to explain the role of the nasal sympathetic vasoconstrictor tone and nasal venous filling pressure in the control of nasal airway resistance and to help explain the periods of unilateral nasal obstruction often associated with allergic and infective rhinitis.

Acute Disease↗

Gender difference in the concentration of the antioxidant uric acid in human nasal lavage.

The entire respiratory tract is continually exposed to a variety of oxidants, of which a large percentage may react within the nasal passages. In the secretions lining the human nasal cavity uric acid has been shown to be the only low molecular weight antioxidant present in abundance. Because this uric acid originates in the plasma, it is possible that factors affecting the levels of plasma uric acid will also alter the levels recovered in lavage fluids. Lavage fluid from 15 men (20-68 years) and 11 women (20-59 years) were collected using a modified Foley catheter which allowed each subject to supply a basal lavage (saline removed immediately after instillation) and an "accrued' lavage (saline left in situ for 5 min) from each nasal cavity. Lavage fluids were assayed for protein, lysozyme and uric acid. The levels of protein and lysozyme in the recovered fluids were found not to be affected by subject age or gender. Uric acid, however, was found to have a weak negative (r2 = -0.685 basal and -0.62 accrued) correlation with age in women, but no such correlation was noted in men. Also, the levels of uric acid in women (1.3 +/- 0.3 microM/L basal and 4.5 +/- 0.6 microM/L accrued) were found to be lower than those seen in men (3.1 +/- 0.6 microM/L basal and 8.4 +/- 1.3 microM/L accrued) (p = 0.0681 and 0.0394 respectively). It is concluded that women have lower levels of uric acid in lavage fluids than men, with subject age also possibly affecting lavage uric acid. It is also proposed that such factors which lead to decreased levels of uric acid may be related to individual sensitivity to inhaled oxidants such as ozone.

Adult↗

Differential depletion of human respiratory tract antioxidants in response to ozone challenge.

The toxicity of ozone, the major component of photochemical smog, is related to its powerful oxidising ability, and many of its deleterious effects are mediated through free radical reactions. As the majority of ozone oxidation events are thought to be confined to the pulmonary epithelial lining fluid, we studied the interaction of ozone with a range of small molecular weight antioxidants found within this compartment: ascorbic acid (AH2), uric acid (UA), and reduced glutathione (GSH). Epithelial lining fluid obtained as bronchoalveolar lavage (BAL) fluid, was taken from 16 male subjects and the antioxidant concentrations determined for each subject. BAL fluid samples from nine of these subjects were then exposed, using an interfacial exposure system, to a range (50-1000 ppb) of ozone concentrations. Both AH2 and UA were consumed by ozone in a time and ozone concentration dependent manner, with mean consumption rates of 1.7 +/- 0.8 and 1.0 +/- 0.5 pmol L-1 s-1 ppb-1, respectively. Considerable intersubject variation was however observed. The individual rates of consumption for each antioxidant were significantly correlated with the respective initial antioxidant concentration. In contrast, although GSH was consumed at 50 ppb ozone, the rate of consumption did not change with increasing ozone concentration. We conclude that there is differential depletion of BAL fluid antioxidants, suggesting a reactivity hierarchy toward ozone in human ELF of AH2 > UA > > GSH.

Antioxidants↗

The effect of changes in ambient temperature on the reliability of acoustic rhinometry data.

The effect of changing ambient temperature on the reliability of acoustic rhinometer data was examined. The acoustic rhinometer was set up in a climate chamber, and connected to a simple cylindrical model containing a constriction. This constriction was at 22.5 cm from the microphone. This would be the position of the tip of a 7.5-cm nose piece, relative to the microphone, when attached to the rhinometer. The ambient temperature was increased from 10 degrees C to 40 degrees C. The position of the constrictions as recorded by the acoustic rhinometer was compared in the same stable model at intervals during the temperature increase. The point of identification of the constriction varied with ambient temperature and the change almost perfectly followed the expected changes in the readings given the relationship of the speed of sound in air to ambient temperature. A shift of approximately 1 mm along the X-axis per 2.5 degrees C change in temperature is seen for this constriction. In a human subject the whole acoustic rhinometry trace would shift along the X-axis to the same degree when using a 7.5-cm nose piece. Volume estimates are calculated between two fixed points on the X-axis and may be profoundly affected by even a small shift of the acoustic reading along this axis. Acoustic rhinometry data should always be collected under the same stable environmental conditions.

Acoustics↗

Rhinitis as a mechanism of respiratory defense.

The incidence of rhinitis is on the increase, especially in towns and cities with high levels of pollution from motor traffic and industry. There is a growing body of evidence which links this increased incidence of rhinitis to chronic nasal irritation from industrial pollution. Studies on the mechanisms of nasal inflammation and the nasal immune response are now providing insights into the etiology of rhinitis. This knowledge will help in the development of therapies aimed at alleviating the symptoms of rhinitis and controlling the development of rhinitis in susceptible individuals. This review discusses some of the factors that may explain the increased incidence of rhinitis and examines basic mechanisms involved in the nasal response to infection and allergy.

Air Pollution↗

Depletion of urate in human nasal lavage following in vitro ozone exposure.

Ozone, a strong oxidant present in summer smog, is thought to primarily react with antioxidant molecules found in the epithelial lining fluid of the respiratory tract. In humans, as much as 40% of inhaled ozone can be removed in the nasal cavity where the major extracellular antioxidant has been identified as uric acid. The present study was undertaken to examine urate/oxidant interactions in human nasal lavage fluid following in vitro exposure to ozone at concentrations relevant to the U.K. Lavage fluid was collected from 8 volunteers using a modified Foley catheter which permits prolonged contact of isotonic saline with the anterior nasal cavity. Nasal lavage samples in multiwell plates were exposed to ozone at concentrations of 50, 100 and 250 ppb. Samples were removed at intervals from 15 to 240 min following exposure and assayed for uric acid depletion. Uric acid concentrations in the nasal lavage were found to fall from 8.52 (time zero) to 3.99 microM, 0.05 and 0.07 microM after 240 min at 50, 100 and 250 ppb ozone respectively. At a non-environmentally relevant ozone concentration of 1000 ppb, uric acid was completely depleted after 60 min. Regression analysis showed a linear correlation between rate of loss of urate and ozone concentration (R2 = 0.97). A novel, non-invasive technique is described to investigate antioxidant compromise and its importance in individual subjects. We conclude that uric acid in nasal lavage samples is scavenged by ozone in a dose and time dependent manner.

Ascorbic Acid↗

External facial dimensions and minimum nasal cross-sectional area.

The relationship of the total minimum nasal cross-sectional area of the decongested nasal cavity to specific, easily measured, facial dimensions was examined. The nasal cavities of 51 healthy volunteers were examined using acoustic rhinometry following nasal decongestant and their minimum nasal cross-sectional area was estimated. This was compared with several personal characteristics, including height and weight, facial width and height, inter-canthal width, and nasal height, alar breadth and the nasal triangular area (half the product of nasal height and alar breadth). The total minimum nasal cross-sectional area showed a good correlation with both the alar breadth, 0.55 (P < 0.0001) and the nasal triangular area, 0.62 (P < 0.0001). No significant correlation was seen with the remaining personal characteristics. The results suggest that it may be possible to produce a clinically useful formula that would be able to predict the expected normal total minimum cross-sectional area of the nasal cavity from these external dimensions. This predicted cross-sectional area could be compared with that measured by acoustic rhinometry. This may prove of value to a clinician wishing to establish if a given patient has a pathologically narrow nasal cavity.

Adolescent↗

A clinical study to evaluate the efficacy of the antihistamine doxylamine succinate in the relief of runny nose and sneezing associated with upper respiratory tract infection.

Antihistamines are widely used in common cold medications, although the role of histamine in the development of common cold symptoms is unclear and the use of antihistamines for the treatment of common cold is controversial. It is clear that antihistamines do not offer a cure for common cold but they may alleviate symptoms of sneezing and runny nose. The present study was designed to investigate the efficacy of an antihistamine, doxylamine, on the symptoms of runny nose and sneezing associated with common cold. We conducted a randomized double-blind study in cold sufferers. One thousand and one volunteers with cold symptoms were screened in four centres (UK, Denmark, Belgium, Germany) and 688 satisfied the entry criteria of the study. The main reasons for excluding subjects were a low nasal secretion weight (secretion weight < 0.2g, 72%) and a low subjective rhinorrhoea score (24%). Volunteers were randomized to receive either doxylamine succinate 7.5 mg by mouth four times a day up to nine doses (n = 345) or placebo (n = 343). The principal measurements were prospectively defined as runny nose and sneezing symptom scores. Data were analysed on an intention-to-treat basis, using Cochran-Mantel-Haenszel statistics controlling for baseline symptom scores. A between-group comparison showed that doxylamine-treated volunteers benefited from a significantly greater reduction in runny nose scores (P < 0.01) and sneezing scores (P < 0.001), than those volunteers in the placebo group. Doxylamine therapy was well tolerated; the incidence of unexpected side-effects was comparable with placebo. Of the expected side-effects, 13.3% of doxylamine-treated patients reported drowsiness. The incidence of sedative effects was lower than has been reported for other commonly used first-generation antihistamines.

Common Cold↗

Errors arising in cross-sectional area estimation by acoustic rhinometry produced by breathing during measurement.

Standardization of acoustic rhinometry is becoming increasingly important as the use of this technique becomes more widespread. The effects of breathing through the nose during acoustic rhinometry were investigated to determine if this affected the measurements of minimal cross-sectional area. During inspiration, and inspiration with the contralateral nasal airway obstructed, the minimal cross-sectional area decreased by 12.48% (p < 0.05) and 56.68% (p < 0.01), respectively, from the measurement made during a breathing pause. During expiration the reverse was observed, with increases in the minimal cross-sectional area of 13.95% (p > 0.05) and 40.20% (p < 0.05), respectively. In all but quiet expiration, the minimum cross-sectional area recorded during respiratory manoevres, differed significantly from those measured during a breathing pause. We recommend that in order to avoid changes in nasal measurements during breathing, acoustic rhinometry should be performed during a brief breathing pause.

Acoustics↗

Menthol and related cooling compounds.

Menthol and related cooling compounds such as 'coolant agent 10', are widely used in products ranging from common cold medications to toothpastes, confectionery, cosmetics and pesticides. The review brings together a range of information on production and chemistry of menthol, and its metabolism, mechanism of action, structure-activity relationships, pharmacology and toxicology. In particular, the coolant action and carminative actions of menthol are discussed in terms of actions on calcium conductance in sensory nerves and smooth muscle. The actions of menthol on the nose, respiratory reflexes, oral cavity, skin and gastrointestinal tract are reviewed.

Animals↗

The opioid agonist codeine and antagonist naltrexone do not affect voluntary suppression of capsaicin induced cough in healthy subjects.

Opioids exert an analgesic action by mimicking the effects of endogenous neurotransmitter substances in the central nervous system. Opioids are widely used as antitussives, and it is reasonable to assume that endogenous opioids are involved in the control of cough. In order to investigate this hypothesis, a parallel design study was carried out to examine the effects of 50 mg codeine (opioid agonist), 50 mg naltrexone (opioid antagonist) and placebo on capsaicin-induced cough in 80 healthy volunteers (mean age 25 yrs). Volunteers received two capsaicin challenge units (each consisting of five inhalations of different concentrations of capsaicin, 0.00-3.33 x 10(-4) M). On one challenge unit subjects were instructed to suppress cough, and on the other challenge unit subjects coughed freely. Coughs were recorded on a tape cassette player and later played back into a pen recorder to produce integrated sound traces. The number of coughs in the suppression challenge unit was significantly reduced in all three treatment groups compared to that recorded in the non-suppression challenge unit. Comparisons between the three treatment groups showed that there was no statistical difference between the three groups both before and 90 min after treatment for the total coughs in the suppression challenge unit and for the total coughs in the non-suppression challenge unit. These results demonstrate that capsaicin-induced cough can be voluntarily suppressed, but that both suppressed and non-suppressed cough were unaffected by treatment with codeine, naltrexone or placebo. These results do not provide any support for the hypothesis that capsaicin-induced cough is influenced by endogenous opioid substances.

Adolescent↗

Voice changes in acromegaly.

The fundamental frequency of 14 patients undergoing hypophysectomy was studied. Eight patients had acromegaly, 3 had a prolactinoma, and 3 had nonfunctioning adenomas. The fundamental frequency of 22 normal, healthy volunteers was measured for comparison. In addition, the external size of the larynx of all patients and volunteers was measured and a relationship between external laryngeal size and the mean fundamental frequency was identified in the volunteers. The mean fundamental frequency in patients with acromegaly was significantly lower than the other 6 patients undergoing hypophysectomy and, in addition, was also lower than the 22 normal volunteers. Postoperatively the fundamental frequency of the acromegalic patients increased rapidly to within the expected normal range. Patients with acromegaly have a lowered fundamental frequency which is most likely due to altered vocal cord mass and elasticity, which is a reversible change. Patients with acromegaly can expect a rapid and complete return of normal fundamental frequency within 2 weeks of surgery to remove the pituitary adenoma.

Acromegaly↗

Sore throat following nasal and oropharyngeal bradykinin challenge.

Nasal challenge with bradykinin has been previously reported to cause sore throat. The aim of the present study was to investigate the mechanism of sore throat by comparing the effects of nasal and oropharyngeal challenge with bradykinin on the sensation of sore throat. Twelve healthy volunteers (6 male, 6 female, mean age 29.9 years), were given nasal followed by oropharyngeal challenge with bradykinin. The nasal and oropharyngeal challenges were separated by 1 week and 1 mg of bradykinin dissolved in 10% ethanol in 0.9% saline was administered as a spray to both nasal passages or to the posterior oropharyngeal wall and tonsillar fauces. The same group of volunteers were also given a control nasal challenge with the ethanol/saline vehicle. Subjects were asked to score symptoms of throat irritation using a ten point visual analogue scale with the extremes labelled 'Worst ever throat irritation' and 'No throat irritation', before and at intervals after bradykinin challenge. Nasal challenge with vehicle did not cause any throat irritation, but both nasal and oropharyngeal challenge with bradykinin caused a significant increase in throat irritation scores at 5 and 15 min following challenge when compared with baseline scores. At 30 min following challenge, the throat irritation scores obtained on nasal challenge were significantly greater than those obtained on oropharyngeal challenge. The results demonstrate that nasal challenge with bradykinin causes a sensation of sore throat which is just as intense as that caused by oropharyngeal challenge and with the sensation of sore throat persisting for a longer period on nasal challenge when compared with oropharyngeal challenge.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Indexing guidelines: applications in use of pulmonary artery catheters and pressure ulcer prevention.

In a busy clinical environment, access to knowledge must be rapid and specific to the clinical query at hand. This requires indices which support easy navigation within a knowledge source. We have developed a computer-based tool for trouble-shooting pulmonary artery waveforms using a graphical index. Preliminary results of domain knowledge tests for a group of clinicians exposed to the system (N = 33) show a mean improvement on a 30-point test of 5.33 (p < 0.001) compared to a control group (N = 19) improvement of 0.47 (p = 0.61). Survey of the experimental group (N = 25) showed 84% (p = 0.001) found the system easy to use. We discuss lessons learned in indexing this domain area to computer-based indexing of guidelines for pressure ulcer prevention.

Abstracting and Indexing↗

The relationship of skin temperature to the nasal cycle in normal subjects.

Nasal airway resistance and skin temperature at the cheek, nose and forearm were measured at 30-min intervals over a period of 7 h in six healthy subjects (age 22-25 years). Right and left skin temperature measurements were made with an infrared thermometer, and right and left nasal airway resistance was measured by active posterior rhinomanometry. Three of the six subjects exhibited what has previously been described as a nasal cycle with spontaneous reciprocal changes in nasal airway resistance. There was a highly significant negative correlation between right and left nasal airway resistance in these subjects (r = 0.64 to -0.78). In contrast to the nasal airway resistance the right and left skin temperatures had highly significant positive correlations (r = 0.74 to 0.93), which demonstrates that the skin temperature changes on each side of the body occurred in parallel with no evidence of a reciprocal relationship. The results indicate that in normal healthy subjects there is no relationship between nasal airway resistance and skin temperature despite the fact that both are controlled by sympathetic vasoconstrictor nerves.

Adult↗

Voluntary suppression of cough induced by inhalation of capsaicin in healthy volunteers.

The aim of the present study was to investigate the voluntary suppression of cough in response to capsaicin inhalation in healthy volunteers, and to determine if the dose-response curve to capsaicin was significantly altered when volunteers were asked to suppress their cough response. The quantification of the degree of voluntary suppression of induced cough could provide a new methodology for screening antitussive agents as antitussives may act by influencing voluntary control of cough. Cough was induced by inhalation of capsaicin. Two challenges were given 5 min apart, each comprising five ascending concentrations of capsaicin (1 x 10(-5) M-3.33 x 10(-4) M). During one of these challenges the volunteer was allowed to cough when required, and during the other they were asked to suppress cough. These two conditions were given in random order. The cough response was recorded by means of a microphone with the integrated sound trace displayed on a chart recorder. A dose-response relationship was obtained on administration of ascending concentrations of capsaicin. In the non-suppressed challenge 23/24 subjects coughed on inhalation of capsaicin (3.33 x 10(-4) M) with a mean number of coughs of 2.92 +/- 0.34, whereas in the suppressed challenge only 3/24 subjects coughed with a mean number of coughs of 0.29 +/- 0.18 (P < 0.001). These results demonstrate that cough induced by inhalation of capsaicin can be voluntarily suppressed. The mechanism of voluntary suppression of cough is discussed in relation to capsaicin challenge and the screening of antitussive medications.

Administration, Inhalation↗

The relationship between nasal airway resistance and middle ear pressure in subjects with acute upper respiratory tract infection.

Middle ear pressure and nasal airway resistance were measured over 7 1/2h in 8 subjects (age 18-32) with symptomatic acute upper respiratory tract infection. The mean middle ear pressure was -13 +/- 1.5 daPa (s.e.m.) with a range between 65 to -140 daPa. The mean total nasal resistance was 0.4 +/- 0.02 Pa/cm3/s (s.e.m.) with a range between 0.20 to 1.28 Pa/cm3/s. Unilateral nasal airway resistance exhibited reciprocal fluctuations with a range between 0.18-3.60 Pa/cm3/s. The mean difference between the highest and lowest unilateral nasal resistance values for each subject was 1.48 +/- 0.22 Pa/cm3/s (n = 16). No correlation was found between unilateral nasal airway resistance and middle ear pressure. Total nasal airway resistance had an inverse correlation with middle ear pressure r = 0.32, r2 = 0.11, n = 176 (p < 0.001). The results indicate that the generation of a negative middle ear pressure in acute upper respiratory tract infection occurred in a manner consistent with intermittent obstruction of the Eustachian tube and gradual middle ear gas absorption. Rapid increases in middle ear pressure and the generation of a positive middle ear pressure were associated with nose blowing. No evidence was found to support the hypothesis that negative middle ear pressures are associated with sniffing.

Adult↗