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Biomedical subjects

G K Scadding

Publications and source records attributed to G K Scadding.

At least 37 records · Page 2Linked to original sources
PubMed1996

Characterization of the bradykinin receptor in the human nasal airway using the binding of [125I]-Hoe 140.

1. The aim of this study was to characterize the kinin receptor in the human nasal airway using [125I]-Hoe 140 binding to a membrane preparation from human nasal turbinates and to compare Ki values from binding displacement by antagonists with the functional effects of these drugs in vivo. We also investigated the effect of Hoe 140 ([D-Arg0, Hyp3, Thi5, D-Tic7, Oic8]-bradykinin), on bradykinin release into the nasal airway. 2. In a membrane preparation from human nasal turbinates removed during surgery, [125I]-Hoe 140 labelled a single, saturable binding site. The equilibrium dissociation constant (at 20 degrees C) for [125I]-Hoe 140 binding to the receptor was 0.46 +/- 0.08 nM. The Bmax was 0.136 +/- 0.003 pmol mg-1 protein and the Hill coefficient was 1.01 +/- 0.07. 3. The association rate constant for [125I]-Hoe 140 binding to the receptor was 0.20 +/- 0.06 nM-1 min-1 and the dissociation rate constant was 0.14 +/- 0.01 min-1. These values were determined at 4 degrees C. The equilibrium dissociation constant calculated from these rate constants was 0.70 nM. 4. Bradykinin and the B2 receptor antagonists, NPC 567, NPC 17731, NPC 17761, [1-adamantane acetyl-D-Arg0, Hyp3, Thi5,8, D-Phe7]-bradykinin, WIN 64338 and Hoe 140 displaced [125I]-Hoe 140 binding: the Ki values from binding displacement are consistent with values expected from a B2 receptor. The B1 agonist, [des-Arg9]-bradykinin and the B1 antagonist, [des-Arg9]-Hoe 140 failed to displace [125I]-Hoe 140 binding at concentrations up to 1 microM. 5. The bradykinin antagonist, Hoe 140, 10 to 200 micrograms, given by intranasal aerosol, produced a dose-related inhibition of the reduction in minimal nasal cross-sectional area (Amin) induced by bradykinin in normal subjects and by house dust mite antigen in subjects with allergic rhinitis to house dust mite. Hoe 140, 10 to 200 micrograms, also caused a dose-related inhibition of the release of albumin into the nasal cavity following challenge with bradykinin. 6. [1-Adamantane acetyl-D-Arg0, Hyp3, Thi5,8, D-Phe7]-bradykinin, 30 to 200 micrograms, caused a dose-related inhibition of the reduction in Amin and the release of albumin into the nasal cavity induced by bradykinin. NPC 567 ([D-Arg0, Hyp3, D-Phe7]-bradykinin) failed to inhibit the reduction in Amin or the release of albumin into the nasal cavity at a dose of 10 mg. 7. Challenge of allergic subjects with house dust mite antigen caused a significant elevation of the bradykinin concentration in nasal lavage fluid and a reduction in Amin. Hoe 140, 100 micrograms, prevented the antigen-induced reduction in Amin and also abolished the antigen-induced increase of bradykinin in nasal lavage fluid. 8. We conclude that there is a B2 bradykinin receptor in the human nasal airway which mediates nasal blockage and plasma extravasation induced by either bradykinin or antigen challenge. It is possible that Hoe 140 inhibits kallikrein in the human nasal airway as well as blocking the B2 receptor.

Adult↗
PubMed1995

The effect of long-term antibiotic therapy upon ciliary beat frequency in chronic rhinosinusitis.

The mucociliary escalator is the first line of defence of the upper and lower respiratory tracts (Greenstone and Cole, 1985; Sleigh et al., 1988). Failure of mucociliary clearance is associated with chronic or recurrent respiratory tract infection. Ten patients with chronic rhinosinusitis underwent nasal brushings for the assessment of ciliary beat frequency. In two no beating cilia were seen; in the remainder the mean value was 9.3 Hz +/- 2.3; range 6.1-12.8 Hz (n = 8). Following three months continuous oral antibiotic therapy repeat nasal brushings demonstrated increased ciliary beat frequencies in all patients, mean value 13.7 Hz +/- 1.6; range 11.5-16.3 Hz (n = 10); (p < 0.01; paired t-test). Depression of mucociliary clearance can occur secondarily to chronic infection and is improved by prolonged antibiotics.

Adolescent↗
PubMed1995

A placebo-controlled study of fluticasone propionate aqueous nasal spray and beclomethasone dipropionate in perennial rhinitis: efficacy in allergic and non-allergic perennial rhinitis.

BACKGROUND: Fluticasone propionate is a new potent, topically active corticosteroid with negligable oral bioavailability. Data on its comparative efficacy in perennial allergic and non-allergic rhinitis are limited. OBJECTIVE: To compare the efficacy and safety of fluticasone propionate aqueous nasal spray (FPANS) 200 micrograms once or twice daily with beclomethasone dipropionate aqueous nasal spray (BPD) 200 micrograms twice daily and placebo in patients with allergic and non-allergic perennial rhinitis. METHODS: The 12-week study had a multicentre, double-blind, randomized, parallel group design. Efficacy was assessed from symptom scores recorded on daily diary cards. RESULTS: FPANS 200 micrograms once or twice daily was significantly better than placebo but not better than BDP in relieving the nasal symptoms of rhinitis. FPANS at either dose was equally effective in the treatment of allergic and non-allergic perennial rhinitis. There were few adverse events and no treatment-related abnormalities in laboratory measurements in either FPANS-treated group. Comparison between treatment groups indicated that FPANS was as well tolerated as placebo and BDP at the doses studied. CONCLUSIONS: In the majority of patients FPANS 200 micrograms once daily in as effective as BDP 200 micrograms twice daily in the relief of perennial allergic rhinitis.

Administration, Intranasal↗
PubMed1995

Intranasal lysine aspirin in recurrent nasal polyposis.

Twenty patients with recurrent nasal polyposis but without any history of aspirin sensitivity were given 2000 micrograms of intranasal lysine aspirin to one nostril and saline to the other once a week for periods of up to 15 months. Two patients had increased nasal obstruction following the initial test doses of lysine aspirin and were excluded from the trial proper. In the remainder symptomatic polyp recurrence was delayed compared with the previous experience while on intranasal steroids, with eight patients remaining symptom free at 15 months compared with an expected number of three (P = < 0.05, chi 2 test). Polyp recurrence was bilateral but there was a tendency for the lysine aspirin treated side to have less polyp tissue as assessed by nasendoscopy and by acoustic rhinometry.

Administration, Intranasal↗
PubMed1995

Reduction by NG-nitro-L-arginine methyl ester (L-NAME) of antigen-induced nasal airway plasma extravasation in human subjects in vivo.

In non-allergic subjects, histamine induced a reduction of minimal nasal cross-sectional area (Amin) and an increase in albumin release into nasal lavage. The effect of histamine on albumin release was inhibited by pretreatment with NG-nitro-L-arginine methyl ester (L-NAME), 1 mumol but not by D-NAME, 1 mumol. L-NAME, 1 and 10 mumol, did not inhibit the histamine-induced reduction of Amin. In subjects allergic to grass pollen, antigen challenge induced a reduction in Amin that was not changed by pretreatment with L-NAME, and an increase in albumin release that was inhibited by L-NAME, 1 mumol. The data support a role for nitric oxide in mediating plasma extravasation in the nose induced by antigen challenge or histamine.

Adult↗
PubMed1994

Association of Gm allotypes with the antibody response to the outer membrane proteins of a common upper respiratory tract organism, Moraxella catarrhalis.

Previously, Gm allotypes have been shown to influence human serum Ig subclass levels as well as the Ab levels achieved after Ag stimulation. The majority of the latter studies have focused on Ab responses to polysaccharide Ags. In this study, we have investigated the relationship between Gm allotypes and naturally occurring serum Ab levels to a bacterial protein Ag, the outer membrane proteins of a common microorganism, Moraxella catarrhalis. In the sera of 160 patients having chronic/recurrent sinusitis, there was a highly significant correlation between the level of specific anti-M. catarrhalis IgG3 level and certain Gm phenotypes. After additional investigation, we found that the presence of G3m(21) homozygosity correlated significantly with lower levels of Ag-specific IgG3. Specific anti-M. catarrhalis IgG3 levels were found to be independent of total serum IgG3 concentrations, and there was no correlation between the serum level of IgG3 and any Gm phenotype. Total IgG and IgG2 that were specific for pneumococcal cell wall polysaccharide also were measured in this group of patients, and no correlation was found between the naturally occurring IgG2 subclass levels to pneumococcal cell wall polysaccharide and the interactive effect of G2m(23) (syn: G2m(n)) and Km(1). Gm allotypes may influence Ab responses other than the anti-carbohydrate responses and, therefore, should be taken into account when investigating IgG subclass responses to protein Ags.

Adolescent↗
PubMed1994

Objective assessment of endoscopic sinus surgery in the management of chronic rhinosinusitis: an update.

Whilst clinical success of endoscopic surgery for chronic rhinosinusitis has necessarily depended primarily upon subjective evaluation, a range of objective techniques are now available which may facilitate our interpretation of results. A group of 200 patients underwent assessment of symptoms by sequential visual analogue scoring, olfaction by qualitative and quantitative testing, nasal airflow by forced inspiratory peak flow, anterior rhinomanometry, nasomucociliary function by ciliary beat frequency and nasal topography by acoustic rhinometry performed pre- and post-operatively. Significant improvement was demonstrated in all symptoms examined, olfactory tests and ciliary beat frequency whilst acoustic rhinometry provided an attempt to quantify the surgical cavities. These results offer an interesting perspective on the pathology of rhinosinusitis and the rationale for surgery within the ostiomeatal complex.

Adolescent↗
PubMed1994

Effect of short-term treatment with fluticasone propionate nasal spray on the response to nasal allergen challenge.

The aim of the study was to investigate the effect of short-term treatment with fluticasone propionate on the response to nasal allergen challenge in patients with allergic rhinitis. Responses to nasal allergen challenge were assessed subjectively by recording symptom scores on visual analogue scales, and objectively by measuring histamine, PGD2 and LTC4 in nasal lavage and by measuring nasal inspiratory peak flow following challenge. Nasal allergen challenge resulted in an increase in all symptom scores (P < 0.05); an increase in histamine and PGD2 (P < 0.05), and a decrease in nasal inspiratory peak flow at 1 h, 5 h and 7 h following challenge (P < 0.05). The allergen-induced changes in symptom scores, mediator levels and nasal inspiratory peak flow were attenuated by treatment with fluticasone propionate (P < 0.05 for all parameters measured). Post-challenge nasal obstruction was decreased by 45%; sneezing, itching and rhinorrhoea by 73, 78 and 80% respectively in the group as a whole comparing scores whilst on fluticasone propionate with those on no therapy. Fluticasone propionate, 200 micrograms twice daily for 2 weeks is effective in reducing significantly the early and late response to nasal allergen challenge.

Administration, Intranasal↗
PubMed1994

Acoustic rhinometry compared with anterior rhinomanometry in the assessment of the response to nasal allergen challenge.

Acoustic rhinometry was used to assess nasal airway patency objectively and was compared with the more established method of anterior rhinomanometry. Ten patients with allergic rhinitis underwent 15 nasal challenges with allergen to which they showed positive skin-prick tests. Responses were assessed by measuring the minimum nasal cross-sectional area (Amin.) using acoustic rhinometry and by measuring nasal airway resistance (NAR) using anterior rhinomanometry. The measurements of Amin. and NAR showed a significant negative correlation. Acoustic rhinometry appears to be superior to anterior rhinomanometry in quantifying the response to nasal allergen challenge and may be particularly useful in patients with initial nasal blockage.

Administration, Intranasal↗
PubMed1994

Reduction by Hoe 140, the B2 kinin receptor antagonist, of antigen-induced nasal blockage.

In subjects with allergic rhinitis to house-dust mite (HDM), antigen challenge produced a significant increase in nasal blockage but had no effect on nasal vascular permeability. The B2 kinin receptor antagonist, [D-Arg0,Hyp3,Thi5,D-Tic7,Oic8]-bradykinin (Hoe 140), 200 micrograms administered by intranasal aerosol 2 min prior to challenge with HDM, 500 u significantly reduced nasal blockage induced by the antigen challenge. The data are compatible with a role for B2 kinin receptors in the nasal response to challenge with antigen which is responsible for nasal blockage.

Adult↗
PubMed1994

Acoustic rhinometry in rhinological practice: discussion paper.

Acoustic rhinometry is a new technique which evaluates nasal obstruction by analysing reflections of a sound pulse introduced via the nostrils. The technique is rapid, reproducible, non-invasive and requires minimal cooperation from the subject. Unlike rhinomanometry it does not require airflow. A graph of nasal cross-sectional area as a function of distance from the nostril is produced, from which several area and volume estimates of the nasal cavity can be derived. The reliability of the method is greatest in the anterior nasal cavity, which is the site of the nasal valve. We have applied the technique to the study of normal nasal physiology in adults and children and to a range of pathological conditions. The role of acoustic rhinometry in diagnosis is somewhat limited compared to nasal endoscopy, but it is useful for nasal challenge and for quantifying nasal obstruction. Monitoring of medical and surgical therapy is a more promising application. In future, acoustic rhinometry is likely to be of particular help in evaluating childhood nasal obstruction, as it is well tolerated by children as young as 3 years old-a group of patients to whom objective tests have hitherto been difficult to apply.

Humans↗
PubMed1994

IgG subclass levels in chronic rhinosinusitis.

Sera from seventy-four adult patients with chronic or recurrent rhinosinusitis (mean duration 10.3 years) were tested for levels of total immunoglobulin and IgG subclasses. Fourteen (19%) had low levels of one of the major immunoglobulin classes and 23 (31%) had one or more IgG-subclass deficiencies, i.e. values less than the mean minus 2 standard deviations of a control population sample. Nineteen patients had low IgG3 levels. The group as a whole showed significantly low mean levels of IgG3, 46.9 +/- 19.5 mg/dl compared to 76 +/- 21 mg/dl for the controls, p < 0.0005 (Student's t-test). Since there was no clinical difference between those with and without IgG3 deficiency, there exists the possibility of an underlying immune defect, possibly involving heavy chain switching, in all these patients.

Adult↗
PubMed1993

The role of acoustic rhinometry in studying the nasal cycle.

The nasal cycle has been demonstrated in man using several techniques, including magnetic resonance imaging, anterior rhinoscopy, rhinomanometry, all of which have limitations due to expense, discomfort, limited scope or poor reproducibility. Acoustic rhinometry is a new technique which analyses nasal geometry throughout the nasal cavity, not just at the flow-limiting segment. Six adult volunteers were examined at 15-to 30-min intervals using acoustic rhinometry. The classical alternating cycle was seen in three subjects, a non-classical cycle was seen in two, and no cycle seen in one subject. Changes occurred throughout the nasal cavity and corresponded with fluctuations in subjective scores of obstruction and, in one case, with nasal resistance measurements. Acoustic rhinometry is a rapid, reproducible and non-invasive technique. This pilot study demonstrates that it has potential for studying in detail the physiology of the nasal cycle.

Acoustics↗