Biomedical subjects

C K Cook

Publications and source records attributed to C K Cook.

8 recordsLinked to original sources

PubMed2004

Treatment with intranasal fluticasone propionate significantly improves ocular symptoms in patients with seasonal allergic rhinitis.

BACKGROUND: If monotherapy with an intranasal corticosteroid can alleviate both nasal and ocular symptoms of allergic rhinitis, treatment may be simplified and costs may be reduced. OBJECTIVE: The purpose of this study was to evaluate the efficacy of once-daily fluticasone propionate (FP) aqueous nasal spray 200 microg compared with vehicle placebo and oral loratadine (LOR) 10 mg in reducing ocular symptoms associated with seasonal allergic rhinitis. METHODS: A total of 471 patients received vehicle placebo, LOR, or FP in this multi-centre, double-blind, double-dummy, randomized study. Patients were > or =12 years old with a history of seasonal allergic rhinitis and a positive skin test for a relevant allergen. During the baseline and treatment periods, patients rated the severity of eye itching, tearing, and redness via visual analogue scales that ranged from 0 (no symptoms) to 100 (most severe symptoms). The three ocular ratings were added to derive the total ocular symptom score (TOSS). Patients with a TOSS > or =120 on at least 4 of the 7 days before the randomization visit were enrolled. The primary outcome was the difference between FP and vehicle placebo in the mean change from baseline in the reflective TOSS overall (averaged over the 28-day treatment period). A difference between FP and vehicle placebo of 25.5 was considered clinically significant. RESULTS: The overall mean change from baseline in the TOSS was significantly greater in the FP group compared with vehicle placebo (clinically significant difference of 28.8; P<0.001) and compared with LOR (difference of 16.2; P=0.028). Overall mean (SEM) changes were -59.9 (5.4) for the placebo group, -72.5 (5.4) for the LOR group, and -88.7 (5.3) for the FP group. The FP treatment group also showed significantly greater overall mean changes in ocular itching, tearing, and redness compared with vehicle placebo (P<0.001) and compared with LOR (P< or =0.045). CONCLUSION: Patients treated with intranasal FP had clinically and statistically significant decreases in ocular symptom scores compared with vehicle placebo. Data also suggest that FP reduced ocular symptoms more than or comparable with oral LOR. Patients experiencing ocular symptoms associated with allergic rhinitis may benefit from monotherapy with intranasal FP.

Administration, Topical↗

PubMed2003

Visual and ocular changes associated with exposure to two tertiary amines.

AIMS: To determine if exposure to dimethylisopropanolamine (DMIPA) and dimethylaminoethanol (DMAE) in a label printing plant was associated with visual disturbances and/or ocular changes. METHODS: Questionnaires, eye examinations (visual acuity, contrast sensitivity at 2.5% and 1.25% contrast, slit lamp biomicroscopy, and pachymetry), and industrial hygiene monitoring for DMIPA and DMAE were performed over a two week period. RESULTS: Eighty nine per cent of line workers reported having experienced blurry vision while at work in the past 12 months, compared to 12.5% of prime workers. A total of 108 full shift personal breathing zone (PBZ) air samples for the amines were collected. The mean time weighted average (TWA) concentration of DMIPA was significantly higher in the line division than in the prime division, as was the mean TWA concentration for total amines. The mean TWA concentration of DMAE was higher in the prime division than the line division. Higher levels of total amines were associated with increased risk of reporting blurry vision, halo vision, and blue-grey vision. The risk of corneal opacity rose with increasing exposure to total amines. The prevalence of corneal opacity also increased with increasing concentration of total amines. Median corneal thickness increased with increasing grades of corneal opacity. There was a statistically significant relation between total amine concentration and increased risk of reduced bilateral visual acuity and 2.5% contrast sensitivity. CONCLUSIONS: Exposure to tertiary amines was associated with blurry, halo, and blue-grey vision, corneal opacity, and decrements in visual acuity and contrast sensitivity at 2.5% contrast.

Amines↗

PubMed2001

Absence of nasal mucosal atrophy with fluticasone aqueous nasal spray.

OBJECTIVE: To evaluate whether 1 year of continuous treatment with intranasal fluticasone propionate would lead to atrophy in the nasal mucosa compared with an active control, oral terfenadine. DESIGN: Prospective, randomized, multicenter, open-label, parallel-group study. SETTING: Two tertiary care academic institutions. PATIENTS: Seventy-five subjects older than 18 years with perennial allergic rhinitis. INTERVENTIONS: Patients received either fluticasone propionate aqueous nasal spray, 200 microg once daily, or terfenadine, 60 mg twice daily, for 1 year. Nasal biopsy specimens were obtained before and after 1 year of treatment and were evaluated for evidence of atrophy. MAIN OUTCOME MEASURES: Epithelial and collagen layer thickness of the nasal mucosa as assessed by light microscopy and the presence and degree of edema, and regularity of collagen fibrils as assessed by electron microscopy. Analyses were performed without knowledge of subject identity or treatment assignment. RESULTS: Neither fluticasone nor terfenadine treatment led to atrophy in the nasal mucosa by clinical or histologic observation. No significant changes from baseline were observed for any assessment of atrophy. In contrast to what would have been expected if atrophy were to occur, mean epithelial layer thickness in the fluticasone group significantly increased compared with terfenadine treatment (P = .03). CONCLUSIONS: Treatment with intranasal fluticasone for 1 year increases the thickness of the nasal epithelium as compared with a year's treatment with terfenadine and does not lead to atrophy in the nasal mucosa. The increased thickness in the fluticasone treatment may represent repair from epithelial damage caused by chronic allergic inflammation.

Administration, Intranasal↗

PubMed2001

Onset of therapeutic effect of fluticasone propionate aqueous nasal spray.

BACKGROUND: The effectiveness of fluticasone propionate (FP) aqueous nasal spray in the treatment of rhinitis has been demonstrated in multiple controlled clinical studies. The onset of therapeutic effect of FP in these clinical trials appears to occur within 12 hours after administration of the initial dose. OBJECTIVE: This article presents an analysis from previous clinical trials that examined the efficacy of intranasal FP in patients with rhinitis to ascertain whether the time to onset of the therapeutic effect of this medication could be determined. METHODS: Completed randomized, double-blind, placebo-controlled studies with FP were evaluated to determine whether onset of effect could be evaluated based on the study designs. A study was deemed acceptable for evaluation of onset of effect if at least one evaluation of the intensity of nasal symptoms was completed within 12 hours after the initial dose of study medication and daily evaluations were made thereafter. Adult patients were included in the onset analysis if they received an initial FP dose of 200 microg. Pediatric patients who received an initial FP dose of 100 microg were also included. Onset of effect was evaluated by 1) examining the timepoints at which statistically significant differences were observed between FP and placebo in mean change from baseline for total nasal symptom score (TNSS); and by 2) using a binary probability model of success/failure to determine statistically significant differences from placebo. RESULTS: Twenty-two studies met the criteria to evaluate onset of therapeutic effect; 3,605 patients with rhinitis received FP and 2,271 patients received placebo. This database represents the largest compilation of data ever assembled to determine the onset of therapeutic effect of a corticosteroid nasal spray. Two studies used a "park design" to examine onset of effect; statistically significant differences in TNSS favoring FP were achieved at hours 2 to 4 and at hour 12, respectively. Using a binary probability model of success/failure for analysis of TNSS in the remaining 20 studies not specifically designed to evaluate onset of effect, numerically greater improvements in TNSS for FP compared with placebo were found in 19 of the 20 studies within 12 hours of the administration of the first dose (P < .001). Pairwise comparisons showed statistically significant improvement for TNSS within 12 hours postdose in five of the studies for FP compared with placebo and in none for placebo compared with FP. CONCLUSIONS: Onset of therapeutic effect occurs within 12 hours, and as early as 2 to 4 hours in some patients, after administration of the first dose of FP aqueous nasal spray.

Administration, Intranasal↗

PubMed1998

A comparison of the efficacy of fluticasone propionate aqueous nasal spray and loratadine, alone and in combination, for the treatment of seasonal allergic rhinitis.

BACKGROUND: Intranasal corticosteroids and oral antihistamines are both effective in the treatment of seasonal allergic rhinitis, although the therapeutic value of administering the two types of agents concurrently has rarely been evaluated. This study was designed to compared the efficacy, safety, and impact on quality of life of fluticasone propionate aqueous nasal spray (FP ANS), loratadine, FP ANS plus loratadine, and placebo (an aqueous nasal spray plus tablet) in the treatment of seasonal allergic rhinitis during the mountain cedar allergy season in south central Texas. METHODS: Six hundred patients with seasonal allergic rhinitis were treated for 2 weeks with either FP ANS 200 microgram once daily, loratadine 10 mg once daily, the FP ANS and loratadine regimens combined, or placebo in a multicenter, randomized, double-blind, double-dummy, parallel-group study. RESULTS: Clinician- and patient-rated total and individual nasal symptom scores after 7 and 14 days of therapy and overall evaluations were significantly lower (P < .001) in the FP ANS and FP ANS plus loratadine groups compared with the loratadine only and placebo groups. Loratadine was not statistically different from placebo in clinician and patient symptom score ratings nor in overall clinician and patient evaluations. FP ANS plus loratadine and FP ANS monotherapy were comparable in efficacy in almost all evaluations; for some patient-rated symptoms the combination was found superior. Mean score changes in the Rhinoconjunctivitis Quality of Life Questionnaire from baseline to day 14 showed significantly greater improvement (P < .001) in quality of life in the FP ANS group than in the group of patients receiving loratadine only or placebo and no significant benefit was demonstrated in the FP ANS plus loratadine group over the FP ANS monotherapy group. No serious or unusual drug-related adverse events were reported. Combining loratadine with FP ANS did not alter the adverse events profile or frequency.

Administration, Intranasal↗

PubMed1996

Comparison of the structural requirements for bacteriochlorophyll binding in the core light-harvesting complexes of Rhodospirillum rubrum and Rhodospirillum sphaeroides using reconstitution methodology with bacteriochlorophyll analogs.

Bacteriochlorophyll (BChl) structural requirements for formation of the core light-harvesting complex (LH1) and its structural subunit complex were examined by reconstitution with BChl analogs and the alpha- and beta-polypeptides of Rhodospirillum rubrum and Rhodobacter sphaeroides. Comparable results were obtained with most of the BChl analogs and the polypeptides of each bacterium, indicating the conservation of BChl binding sites. These systems showed the following common requirements for formation of the subunit complex and LH1: (1) Mg or a metal of similar size and coordination chemistry (e.g., Zn, Cd, Ni), (2) a bacteriochlorin oxidation state of the macrocyclic ring, (3) a 13(2)-carbomethoxy group, and (4) an intact ring V. Some structural features were not as critically important. For example, the subunit complex and LH1 could be formed with both sets of polypeptides and BChl b, as well as with analogs containing either short (ethanol) or long (phytol) esterifying alcohols. Two derivatives were identified that behave differently with the two sets of polypeptides. The 3-acetyl group is required to form LH1 in both bacteria, although a subunit-type complex was readily formed with [3-vinyl]BChl a and the polypeptides of Rs. rubrum but formed only slightly under special conditions with polypeptides of Rb. sphaeroides. [13(2)-OH]BChl a(p) formed both subunit- and LH1-type complexes with the alpha- and beta-polypeptides of Rb. sphaeroides but not with those of Rs. rubrum. Thus, some subtle differences in the BChl binding sites exist in the LH1 complexes of these two bacteria.

Amino Acid Sequence↗

PubMed1996

Intranasal fluticasone propionate inhibits recovery of chemokines and other cytokines in nasal secretions in allergen-induced rhinitis.

BACKGROUND: Allergen-induced nasal responses are associated with the recovery of proinflammatory mediators and cytokines. In recent years, a distinct group of chemotactic cytokines, chemokines, has been the focus of intense investigation as to their possible role in the pathogenesis of allergic diseases. Although corticosteroids have been known to be effective in the treatment of allergic diseases, their mechanism(s) of action has not been fully elucidated. OBJECTIVES: To study the effect of topical fluticasone on the recovery of chemokines (IL-8, MIP-1 alpha, and RANTES) and other cytokines (IL-1 beta, IL-6, and GM-CSF) from nasal mucosa following allergen challenge. To correlate the improvement of rhinitis symptoms with cytokine levels during early-phase and late-phase allergic responses. METHODS: A randomized, double-blind, placebo-controlled crossover study of fluticasone propionate, 200 micrograms q d, was performed in ten subjects with allergic rhinitis. Allergen challenge was administered after 1 week of treatment. Nasal secretions were collected immediately after challenge and during the late-phase reactions; symptom scores were recorded simultaneously. Nasal cytokines were assayed by specific ELISA. RESULTS: The allergen challenge caused early-phase and late-phase allergic reactions and increased recovery of IL-1 beta, IL-6, IL-8, RANTES, MIP-1 alpha, and GM-CSF from the nasal mucosa. Intranasal fluticasone inhibited the allergen-induced increase in nasal symptoms. This was associated with decreases in cytokine recovery. A significant correlation was observed between decreases in cytokine levels and in symptom scores after treatment. CONCLUSION: Our results suggest that treatment with topical fluticasone propionate inhibits allergen-induced nasal responses and the associated increase in the production/secretion of chemokines and other proinflammatory cytokines.

Administration, Topical↗

PubMed1979

The nasopharyngeal soft tissue sign: a reappraisal.

An increase in the thickness of the soft tissues of the posterior nasopharyngeal wall has been described in patients with a fracture of the skull base (Andrew, 1978). Measurements of this soft tissue layer made in the same way, in Southampton, have shown a striking difference in the mean and in the normal range both in adolescents and adults. The normal measurements overlap those found in patients with a fracture of the skull base and the sign is not therefore a reliable indication of the presence of such a fracture.

Adolescent↗