PubMed Health⌕ Search

Biomedical subjects

W J Doyle

Publications and source records attributed to W J Doyle.

At least 19 recordsLinked to original sources
PubMed1992

Third-generation cephalosporins in the treatment of acute pneumococcal otitis media. An animal study.

There is concern that third-generation cephalosporins may not be effective in the treatment of acute otitis media due to Streptococcus pneumoniae. Using the chinchilla animal model, we compared two third-generation cephalosporins, cefixime (Suprax) and ceftibuten (investigational), with ampicillin and saline controls in an investigator-blinded, randomized trial. Whereas the saline controls performed worse than all other groups, no significant differences were detected among the three antibiotics regarding the time required to sterilize the middle ear cleft, or the prevalence of positive cultures after 10 days of therapy. The statistical power of the comparisons of cefixime and ceftibuten with ampicillin were 98% and 67%, respectively. The results of this in vivo animal study fail to support the contention that the two third-generation cephalosporins investigated are not effective in the treatment of pneumococcal acute otitis media. Caution is advised when extrapolating these results to the general clinical setting.

Acoustic Impedance Tests↗
PubMed1992

Inhibition of lymphoproliferation by middle ear effusion in experimental otitis media.

In this study, experimental otitis media was created in the chinchilla by direct middle ear challenge with Escherichia coli endotoxin, Streptococcus pneumoniae, Haemophilus influenzae, or Pseudomonas aeruginosa. The effusions recovered from the chinchillas in all four challenge groups were shown to inhibit the lymphoproliferative response of chinchilla peripheral blood lymphocytes to stimulation with phytohemagglutinin. The effect was dose dependent, and for effusions of infectious origin, the degree of inhibition was directly related to the duration of infection. Presence of the inhibitor in plasma was undocumented, suggesting a local production within the middle ear. Lymphocytes from middle ears infected with bacteria but not middle ears challenged with endotoxin were hyporesponsive or nonresponsive to stimulation with phytohemagglutinin. These results confirm the presence of an inhibitor of the lymphoproliferative response in experimental otitis media of different etiologies.

Animals↗
PubMed1992

Otologic effects of interferon beta serine in experimental rhinovirus colds.

To evaluate the efficacy and otologic effects of recombinant interferon beta serine for experimental rhinovirus colds, 38 healthy adults received nasal drops of recombinant interferon beta serine, 12 x 10(6) U, or placebo three times daily for 4.3 days beginning 36 hours after infection. Illness rates and severity did not differ between the groups, but the frequency of virus shedding was reduced on the fourth (37% vs 74%) and sixth (11% vs 42%) postchallenge days in recipients of recombinant interferon beta serine. Abnormal eustachian tube function in at least one ear was identified by the inflation-deflation test during 44% of observations in 13 infected recipients of recombinant interferon beta serine compared with 62% of observations in five placebo recipients. Tympanometry revealed middle-ear pressure abnormalities (less than -50 or greater than 20 mm H2O) in at least one ear during 18% of observations in recipients of recombinant interferon beta serine compared with 38% of observations in placebo recipients. These results suggest that antiviral therapy may alter the course of middle-ear dysfunction associated with experimental colds.

Administration, Intranasal↗
PubMed1992

Physiologic abnormalities in the paranasal sinuses during experimental rhinovirus colds.

Six (18%) of 34 healthy, asymptomatic young adults had mucosal thickening or fluid in the paranasal sinuses on screening magnetic resonance imaging (MRI) examination. When 19 of these subjects were challenged with rhinovirus, 18 became infected. Twelve of the 18 infected subjects had technically satisfactory serial MRI examinations, and four (33%) of these developed MRI abnormalities of the ethmoid or antral sinuses that were temporally associated with the acute infection. The mean total nasal secretion weights were 22 gm/5 days in the four subjects whose MRI abnormalities were associated with the acute infection compared with 5.5 gm/5 days in the eight subjects who had normal MRI examinations during the acute infection (p = 0.06). Abnormalities of the paranasal sinuses, which were associated with increased volumes of nasal secretion, were detected by MRI examination during rhinovirus infection. These abnormalities may have a role in the pathogenesis of acute sinusitis associated with colds.

Acute Disease↗
PubMed1992

Rhinovirus 39 infection in allergic and nonallergic subjects.

To determine if individuals with allergic rhinitis are hyperresponsive to upper respiratory tract viral infections, 20 allergic and 18 nonallergic, susceptible, adult volunteers were challenged and infected with rhinovirus type 39 before the pollen seasons. Before challenge and on each of 6 days of cloister, all volunteers were interviewed for symptoms and completed a test battery consisting of evaluations of secretion production by weighed tissues, nasal patency by active posterior rhinomanometry, nasal clearance by the dyed saccharin technique, pulmonary function by spirometry, eustachian tube function by sonotubometry, and middle ear status by tympanometry. The symptomatology and pathophysiology resulting from the rhinovirus infection were consistent with those reported in previous studies with this challenge system. Between-group comparisons revealed no differences in symptom presentation, nasal secretion production, or overall pathophysiologic response. However, for decreased mucociliary clearance rate, increased nasal congestion, eustachian tube dysfunction, and symptoms of sneezing, the allergic group demonstrated an earlier onset compared with that of the nonallergic group. The biologic significance of the differences in onset of dysfunction is tempered by the observation that the temporal pattern of responses in the allergic group was similar with that of nonallergic subjects in previous studies. The results of the present study do not support the hypothesis of a physiologic hyperresponsiveness to rhinovirus type 39 infection in allergic subjects during nonallergy seasons.

Humans↗
PubMed1992

Experimental otitis media evaluated by magnetic resonance imaging: an in vivo model.

The use of magnetic resonance imaging in otitis media research is being explored in our laboratory. In this study, we present a new method for studying changes in the middle ear cleft due to an episode of induced otitis media in the chinchilla model. It uses gadolinium-diethylenetriamine pentaacetic acid, a magnetic resonance imaging contrast agent, to examine the uptake and washout characteristics of middle ear mucosa during an inflammatory episode. Parameters such as the time to maximum intensity of the mucosa and the washout rate of the contrast agent from the mucosa were significantly correlated to the duration of the infection.

Animals↗
PubMed1991

Assessment of middle-ear status during experimental otitis media using magnetic resonance imaging.

Magnetic resonance imaging has proved to be a useful tool for in vivo imaging of a variety of tissues. In this study, magnetic resonance imaging was applied to the middle ear of experimental animals with otitis media. Results showed that the presence and distribution of effusion within the middle-ear space could be readily determined. Moreover, following injection of gadolinium-diethylenetriaminepentaacetic acid, a contrast agent, the inflamed middle-ear mucosa could be resolved. A comparison between magnetic resonance imaging and tympanometry with respect to the diagnosis of effusion showed that negative pressure tympanograms were equivocal (50% effusion) and that flat or normal tympanograms were in error in approximately 20% of the observations. These data document a role for magnetic resonance imaging in in vivo studies of the pathogenesis of otitis media with effusion.

Acoustic Impedance Tests↗
PubMed1991

Neonatal conductive hearing loss does not compromise brainstem auditory function and structure in rhesus monkeys.

The effect of conductive hearing loss on the maturation of the auditory pathway was evaluated using the auditory brainstem response (ABR) in rhesus monkeys. Ten newborn rhesus monkeys were assigned to control (N = 4), unilateral hearing loss (N = 3), or bilateral hearing loss (N = 3) groups. Hearing loss was created by surgically excising a 3 mm section of the external auditory canal and suturing the canal. Auditory brainstem responses to click stimuli were recorded prior to and after the surgical procedure and bi-monthly or monthly for a 14 month follow-up period. Results showed that after surgery all ears developed an estimated 30-50 dB conductive hearing loss which was retained throughout the follow-up period. Contrary to expectations, the latencies of the ABR component waves decreased with age in all ears. When adjusted for hearing level, there were no differences between ears in maturation of the component waves of the ABR. These data suggest that, in primates, a conductive hearing loss does not affect the maturation of those aspects of the auditory pathway reflected in the ABR. Furthermore, the conductive losses were not accompanied by any discernible change in the neuronal sizes of brainstem auditory neurons or the volume of the cochlear nuclei.

Animals↗
PubMed1991

Effect of terfenadine on nasal, eustachian tube, and pulmonary function after provocative intranasal histamine challenge.

Previous studies have documented that intranasal histamine challenge results in nasal and eustachian tube obstruction (ETO) in human volunteers. The purpose of the present study was to assess the effect of pretreatment with terfenadine, a nonsedating antihistamine on the pathophysiologic consequences of intranasal histamine challenge. Fifteen subjects with allergic rhinitis were challenged intranasally with saline and increasing histamine doses (0.01, 0.1, 0.5, 1.0, 5.0, and 10.0 mg) before pretreatment (baseline) and after 1 week of pretreatment with terfenadine, 60 mg b.i.d., terfenadine, 120 mg b.i.d., and placebo. Nasal conductance as measured by posterior rhinomanometry showed a dose-dependent, monotonic decrease following sequential administration of the histamine solutions, but there were no apparent differences in the average responses among the four challenge sessions. The frequency of ETO after histamine challenge was decreased by pretreatment with both doses of terfenadine, although this was not significant. Histamine-induced sneezing and rhinorrhea, but not congestion, were significantly reduced by terfenadine pretreatment. There was no evidence of extension of the histamine effects to the lower airway. The results of the present study suggest that terfenadine, a nonsedating antihistamine, had a favorable effect on sneezing and rhinorrhea after provocative intranasal histamine challenge, but did not significantly attenuate the subjective or objective nasal and ET obstructive responses.

Administration, Intranasal↗
PubMed1990

Physiologic responses to intranasal dose-response challenges with histamine, methacholine, bradykinin, and prostaglandin in adult volunteers with and without nasal allergy.

The dose-response (dose, 0.01, 0.05, 0.1, 0.5, 1, and 5 mg) profiles of 10 atopic and 10 nonatopic subjects were determined for nasal patency, secretion weight, pulmonary function, eustachian tube function, middle-ear function, and symptoms after intranasal inhalation challenges with histamine, bradykinin, methacholine, prostaglandin D2, and prostaglandin F2 alpha (PGF2 alpha). Results demonstrated that challenge with PGF2 alpha increased nasal patency, whereas challenge with all other substances decreased patency. The relationship between substances in eliciting a nasal congestive response was prostaglandin D2 greater than histamine greater than bradykinin greater than methacholine. A similar effect ordering was noted for the postchallenge development of eustachian tube dysfunction. Secretion weights were significantly greater after challenge with histamine compared to all other substances. A decrease in pulmonary function was observed only after challenge with PGF2 alpha, although the effect was not statistically significant. No changes in middle-ear pressure were observed for challenges with any of the substances. Only histamine challenge provoked sneezing, whereas challenge with either of the prostaglandins provoked cough. With the exception of methacholine, all substances caused symptoms of rhinorrhea, congestion, and sore throat. Bradykinin was particularly effective in provoking "pain/pressure"-related symptoms. With the exception of secretion weight, the differences between responses of atopic and nonatopic subjects were not statistically significant. These results document mediator specificity in the physiologic and symptomatic responses to intranasal challenge.

Adolescent↗
PubMed1990

A randomized controlled trial of glucocorticoid prophylaxis against experimental rhinovirus infection.

The effects of combined intranasal and systemic glucocorticoid steroids on the local inflammatory response, and symptoms due to experimental rhinovirus infection were studied in 45 adults randomized to prophylaxis with either placebo or steroids. Intranasal beclomethasone (168 micrograms twice a day) was begun 4 days before viral challenge and continued 5 days after challenge. Oral prednisone (30 mg twice daily) was given for 3 days beginning 1 day before challenge. During the first 48 h after viral inoculation, nasal obstruction, nasal mucus weights, and kinin concentrations in nasal lavages were lower in steroid recipients, but subsequent increases in these variables in the steroid group resulted in no significant cumulative differences between treatment groups. These data suggest that steroid prophylaxis may suppress nasal inflammation and cold symptoms during the first 2 days in experimental rhinovirus colds.

Administration, Intranasal↗
PubMed1990

Nasal physiology and inflammatory mediators during natural pollen exposure.

Nasal allergen challenges in allergic rhinitis subjects provoke characteristic alterations in nasal and eustachian tube (ET) function. The purpose of this study was to examine the effect of natural pollen exposure on nasal physiology and inflammatory mediators. Grass pollen counts, ET function (sonotubometry), nasal resistance (rhinomanometry), symptoms, mediator levels (saline wash), and skin test reactivity in nine adults with grass allergy were monitored weekly before (week 1), during (weeks 2 to 9) and after (weeks 10 and 11) grass pollen season. Pollen counts peaked at week 3, and then decreased gradually. Mean nasal resistance (cm H2O/L/sec) increased from a baseline of 2.4 +/- 0.5 to 3.7 +/- 1.1 at week 3, peaked at week 4 (5.3 +/- 1.2), remained elevated (weeks 5-8), peaked again at week 9 (6.6 +/- 1.4), and then decreased, Bilateral ET obstruction was not present in any of the subjects at baseline, but was present in five of the nine subjects at week 4. Symptom severity paralleled grass pollen counts. Peak mediator levels were observed at weeks 2 and 9 for histamine and at weeks 3 and 10 for leukotriene C4. Seasonal increases in grass and histamine-induced wheal sizes were also observed. These data show that measurable changes in the function of the nose and ET and the levels of nasal mediators and dermal reactivity accompany and track pollen counts during seasonal exposure and suggest that therapy for seasonal allergic rhinitis should be (1) directed at reducing airway inflammation and (2) continued well beyond the time of peak pollen exposure.

Adult↗
PubMed1989

Alterations of the eustachian tube, middle ear, and nose in rhinovirus infection.

This study measured the changes in 64 ears of 32 adult volunteers in eustachian tube function by the nine-step test, middle ear pressure by tympanometry, and nasal patency by active posterior rhinomanometry for 18 days following type 39 or Hanks rhinovirus infection. Abnormal measures were limited to the 75% of subjects (24) with clinical illness (colds) defined by symptom scores. Two days after infection, tubal function was present in only 50% of ears (48) and 20% of persons (5), middle ear underpressures of less than -50 mm H2O were measured in 50% of volunteers (12), and decreased nasal patency was observed in 54% of those with colds (13). These changes resolved 6 to 10 days after challenge. These results support a causal relationship between viral upper respiratory tract infection eustachian tube obstruction and abnormal middle ear pressure.

Acoustic Impedance Tests↗