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Biomedical subjects

W J Doyle

Publications and source records attributed to W J Doyle.

At least 37 records · Page 2Linked to original sources
PubMed1999

A model to explain the rapid pressure decrease after air-inflation of diseased middle ears.

OBJECTIVES: Air-inflation in humans and monkeys with significant negative middle ear pressure or with middle ear inflammation was shown to cause greater than ambient middle ear pressure initially, followed by a rapid rate of pressure decrease to approach the preinflation value. STUDY DESIGN: A mathematical model of middle ear pressure regulation is presented and used to simulate air-inflation of the normal and diseased middle ear. MATERIALS AND METHODS: The model represents the total volume of the middle ear as consisting of three subcompartments representing the airspace, effusion, and mucosa/blood. Gas exchange among those compartments was assumed to be diffusion limited, and the gas exchange between the mucosa/blood compartment and systemic blood was assumed to be perfusion limited. Disease was modeled as an increase in mucosal blood flow or, alternatively, as an increase in the volumes of the effusion and mucosa/blood compartments. RESULTS: The predictions of the model agree better with the experimental data when the increased rate of pressure change after middle ear inflation in diseased ears is driven by an increased volume of the effusion compartment as opposed to an increased perfusion rate. The responsible mechanism is a rapid redistribution among subcompartments of the gas volume introduced into the air compartment. CONCLUSIONS: These results suggest that middle ear inflation with inert gas can be used to diagnose the presence and relative amount of middle ear effusion, and that current protocols for treating otitis media with effusion using inflation need to be modified to optimize their intended effect.

Animals↗
PubMed1999

Illness and otological changes during upper respiratory virus infection.

OBJECTIVES: Upper respiratory virus infection is associated with the expression of symptoms and signs of illness, and with the development of complications in anatomically contiguous structures. In most epidemiological studies, the frequency of the various complications is expressed as a fraction of the total population judged to be ill by report, signs, or symptoms. Because not all infected subjects become ill and because infected non-ill subjects may develop complications, such risk estimates could be inaccurate. The objective of this study was to estimate the magnitude of the presentation bias during controlled, experimental infections. STUDY DESIGN: This was a prospective, experimental study of the relationship between illness and otological complications during experimental upper respiratory virus infection in 316 adult volunteers. METHODS: The data for illness and for abnormal middle ear underpressure in adult (18-54 y) volunteers experimentally infected with one of three viruses (rhinovirus type 39, rhinovirus strain hanks, influenza A virus) were analyzed and expressed as the relative frequencies of infected subjects reporting illness, developing abnormal middle ear pressure, and developing abnormal middle ear pressure in the absence of illness. RESULTS: For all three viruses, illness was documented in approximately 50% of the infected subjects. While the frequency of persons developing abnormal middle ear underpressure was greater in the infected-ill subjects, approximately one third of all infected subjects developing that complication did not report illness. CONCLUSIONS: These results support a large presentation bias in epidemiological surveys of viral upper respiratory infections, and infer that those surveys underestimate the true frequency of complications resulting from such infections.

Adolescent↗
PubMed1999

Repeated inflation does not prevent otitis media with effusion in a monkey model.

OBJECTIVE: Investigate the efficacy of repeated middle ear inflation with an inert gas (argon) for preventing the development of middle ear effusion in monkeys with functional eustachian tube obstruction. STUDY DESIGN: Prospective controlled trial of daily middle ear inflation with five monkeys assigned to the inflation group and four to the control group. METHODS: The right tensor veli palatini muscle of nine monkeys was paralyzed with botulinum toxin. Tympanometry was done before the procedure and then daily for 21 days. Presence and distribution of effusion were assessed before paralysis and on day 15 using magnetic resonance imaging (MRI). In five right ears inflation was done beginning at the first observation of negative middle ear pressure of < or =200 mm H2O and repeated on all days with pressures < or =-100 mm H2O. Four right ears served as uninflated controls. RESULTS: Right middle ear pressure decreased in all animals over the course of the study. Pressure returned to near-ambient levels immediately following the argon inflation but was decreased to control levels at the subsequent observation on the following day. MRI at day 15 documented effusion in all right ears with no quantifiable differences in amount or distribution between ears that were and were not inflated with argon. CONCLUSIONS: Repeated inflation with an inert gas does not prevent middle ear effusion in monkeys with functional eustachian tube obstruction.

Animals↗
PubMed1999

MRI validation of the accuracy of tympanometric gradient for the diagnosis of OME.

Tympanometry provides a rapid, non-invasive and objective assessment of middle ear (ME) status and is widely used for the clinical diagnosis and follow-up of otitis media with effusion (OME). ME pressure, acoustic admittance and tympanometric gradient are the main test parameters used in making assignments to diagnostic classes (i.e. presence or absence of effusion, effusion quantity). Of these, the tympanometric gradient was suggested to be more sensitive to the presence of effusion, but this has not been demonstrated conclusively and no standard definition of that gradient is accepted. In this study, 10 cynomolgus monkeys with experimental OME were used to compare the diagnosis of OME made using three different methods to estimate tympanometric gradient with that provided by simultaneous magnetic resonance imaging (MRI) of the ME. All three methods of tympanometric gradient measurement were highly correlated with the quantity of ME effusion measured by the MRI. Although not significant, the MRI results were better correlated with those for the 'width' method when compared to either the 'difference' or the 'ratio' method of gradient estimation. This study demonstrates the use of MRI as a gold standard for evaluating the accuracy of other methods to diagnose ME effusion.

Acoustic Impedance Tests↗
PubMed1998

Daily tympanometry in children during the cold season: association of otitis media with upper respiratory tract infections.

The causal association between otitis media and viral upper respiratory tract infections (URI) suggests that early intervention during the course of a viral URI could prevent many episodes of otitis media. However, the feasibility of this approach can not be assessed at present since many aspects of the epidemiology and natural history of URI-associated otitis media are undefined. To address this deficiency, daily monitoring of middle ear status (tympanometry) and cold symptoms and weekly pneumatic otoscopy were done on a pilot cohort of 20 children. These children, between the ages of 2 and 6, were followed from November 1996 to April 1997. Compliance with symptom diaries was 85%, with tympanograms was 90%, and with weekly physician visits was 70%. During the study period, there were 53 'colds' (average 2.65 per child) and 28 new episodes of middle ear effusion (10 unilateral and 9 bilateral). Overall, 47.3% of the tympanograms were Type A, 17.2% Type C1, 9.4% Type C2, and 21.8% Type B. Children who developed MEE during the study spent more time with abnormal MEP (either MEP < -150 or flat) during both cold and healthy days than children who did not develop MEE. Temporally, during colds, high negative pressures preceded the development of Type B tympanograms in children who developed middle ear effusions. Children who did not develop effusions still had high negative pressures during colds, but recovered to a normal pressure within days. These observations document the feasibility of this investigational format for study of the sequential changes in middle ear status before, during and after a URI.

Acoustic Impedance Tests↗
PubMed1998

Types of stressors that increase susceptibility to the common cold in healthy adults.

Two-hundred seventy-six volunteers completed a life stressor interview and psychological questionnaires and provided blood and urine samples. They were then inoculated with common cold viruses and monitored for the onset of disease. Although severe acute stressful life events (less than 1 month long) were not associated with developing colds, severe chronic stressors (1 month or longer) were associated with a substantial increase in risk of disease. This relation was attributable primarily to under- or unemployment and to enduring interpersonal difficulties with family or friends. The association between chronic stressors and susceptibility to colds could not be fully explained by differences among stressed and nonstressed persons in social network characteristics, personality, health practices, or prechallenge endocrine or immune measures.

Adolescent↗
PubMed1998

Exchange rates of gases across the tympanic membrane in rhesus monkeys.

The exchange rates of CO2 and He across the tympanic membrane were estimated in 5 monkeys. For these experiments, the monkey was anesthetized and one arm of a polyethylene "T" tube was introduced into the external canal of the test ear and sealed to the ambient environment with wax. One arm of the T tube was attached to a pressure transducer and the other to an argon gas source via a valve. Silica tubing sealed within the probe provided periodic gas samples for composition analysis by an online mass spectrometer. Prior to each experiment, the probe was washed with Argon. In 5 experiments the probe was sealed within the external canal of animals with physiological middle ear gas compositions, and in 5 experiments the probe was sealed within the external canal of animals whose middle ears were partially washed with He. The gas in the probe was sampled and analyzed at 10-min intervals for up to 4 h. The results documented a significant increase in the percentage composition of CO2 but not He in the experiments conducted with physiological middle ear gas compositions, and increases in both He and CO2 in the experiments conducted after the middle ear was washed with He. Estimated, average exchange constants for He and CO2 were 0.0005 microl/min/mmHg and 0.0103 microl/min/mmHg, respectively. Using data from previous experiments, the relative trans-mucosal to trans-tympanic membrane gas exchange rates in monkeys are estimated to be in the order of 10:1 for inert gases and 180:1 for chemically active gases.

Animals↗
PubMed1998

Prechallenge antibodies moderate disease expression in adults experimentally exposed to rhinovirus strain hanks.

This double-blind study determined the influence of serum neutralizing antibody titers on the rate of infection and magnitude of disease expression after experimental exposure of adult volunteers to rhinovirus strain Hanks (RV-H). A total of 133 healthy volunteers were tested for antibody status, cloistered for a 6-day period, and challenged with RV-H at the end of the first cloister day. On these days, response to viral challenge is assessed with symptom diaries and physical examinations. The low-titer infected group was significantly different from the intermediate-titer infected and the uninfected groups in terms of postchallenge nasal and throat symptoms, expelled secretion weights, nasal mucociliary clearance rates, and frequency of negative middle ear pressures. A similar trend held for the infected high-titer vs. low-titer group comparisons. These data show that high homotypic serum neutralizing antibody titers are associated with protection from infection and lessened signs and symptoms following experimental RV-H exposure.

Adult↗
PubMed1998

Effect of rimantadine treatment on clinical manifestations and otologic complications in adults experimentally infected with influenza A (H1N1) virus.

Susceptible adults (n = 105) were enrolled into a randomized double-blind study of rimantadine treatment of experimental influenza A infection. Subjects were cloistered for 8 days and challenged with a rimantadine-sensitive strain of influenza A H1N1 virus at the end of the first day. Forty-eight hours after challenge and for 8 days, 54 subjects received placebo and 51 received rimantadine (100 mg orally, twice a day). Symptoms, signs, and pathophysiologies were monitored. Nine subjects were not infected. Seventeen subjects (38%) in the rimantadine and 26 (53%) in the placebo group became ill. A beneficial effect of rimantadine was documented for virus shedding, symptom load, and sinus pain. Rimantadine had no effect on nasal patency, mucociliary clearance, nasal signs, or on symptoms and signs of otologic complications. These results do not support a preventive effect of rimantadine on the development of otologic manifestations of influenza A infection in adults.

Adolescent↗
PubMed1998

Rhinovirus infection induces mucus hypersecretion.

Rhinorrhea is a prominent symptom of the common cold. Although increases in vascular permeability and serous cell secretion have been demonstrated in human nasal mucus during active rhinovirus infections, changes in mucin constituents have not been quantified. Nonallergic (n = 48) and asymptomatic allergic rhinitis (n = 32) subjects were inoculated with rhinovirus type hanks before the spring allergy season. Nasal lavages were performed before inoculation (day 0), then daily for 5 days afterward. The subjects were divided into infected and noninfected groups on the basis of evidence of successful rhinovirus infection (nasal shedding of virus or fourfold increases in specific serum antibodies). Concentrations of interleukin (IL)-8, markers of vascular leak (IgG), seromucous cells (lysozyme), and mucoglycoprotein exocytosis [7F10-immunoreactive mucin (7F10-irm) and Alcian blue staining of acidic mucoglycoproteins] were measured in lavage fluids. The infected subgroup had maximal increases in nasal lavage fluid concentrations of IL-8 (sevenfold), IgG (fourfold), total protein (twofold), and gel-phase 7F10-irm (twofold) on day 3. There were no differences between infected allergic and nonallergic subjects. IL-8 and gel-phase 7F10-irm were significantly higher in infected than in noninfected subjects. In addition to promoting plasma exudation, rhinovirus hanks infection increases IL-8 and gel-phase mucin secretion. These processes may contribute to a progression from watery rhinorrhea to mucoid discharge, with mild neutrophilic infiltration during the common cold.

Adolescent↗
PubMed1998

Expression of acute otitis media after receptor blockade of platelet activating factor, thromboxane, and leukotrienes in the chinchilla.

To determine the role of inflammatory products of phospholipid metabolism in acute otitis media (AOM), we infected 128 chinchillas with Streptococcus pneumoniae and randomly assigned them to one of four equal-sized treatment groups receiving intramuscular ampicillin sodium (control) or intramuscular ampicillin plus receptor blockers of platelet activating factor (WEB 2086, 5 mg/d orally), of leukotriene (MK 571, 0.5 mg/d orally), or of thromboxaneA2 (GR 32191B, 5 mg/d orally). All treatments were begun on day 2 postinoculation and continued for 10 days. On days 3, 6, 9, and 12, 8 animals from each group were sacrificed. Effusions were recovered for biochemical assay, and the right middle ears were prepared for histologic study. Differences among groups in the number of ears with effusion or in effusion volume were not statistically significant. In comparison to the control group, mucosal thickness and the number of ears with histopathologic signs of inflammation were significantly less in the GR and WEB treatment groups, but not the MK group. Also, effusion concentrations of free fatty acids, protease, and hydrolytic enzymes were significantly less in those groups. These results show that the addition of a receptor blocker for either platelet activating factor and/or thromboxane to ampicillin in the treatment of AOM reduces mucosal inflammation and decreases the production of other inflammatory chemicals. The failure of a receptor blocker of leukotrienes to moderate disease expression suggests either a less important role for these chemicals in AOM or an insufficient bioavailability of the specific MK 571 inhibitor. These results confirm that platelet activating factor and thromboxane are active mediators of inflammation in AOM.

6-Ketoprostaglandin F1 alpha↗
PubMed1998

Upregulation of messenger RNA for inflammatory cytokines in middle ear mucosa in a rat model of acute otitis media.

A rat model for acute otitis media has been established and was used to delineate the temporal expression of messenger RNA for key inflammatory cytokines. Inoculation with live Streptococcus pneumoniae induced a rapid expression of tumor necrosis factor alpha (within 6 hours) followed by upregulation of message for interleukin (IL)-6 (peak at 12 to 24 hours, remaining elevated through 120 hours) and IL-10 (peak at 24 hours). Inducible nitric oxide synthase message was also selectively increased following live bacterial inoculation (peak at 12 to 24 hours). Although there was a detectable inflammatory response to killed bacteria, it was minimal, was of short duration, and preceded the peak for live bacteria; only expression of IL-6 was significantly increased in this group (peak at 12 hours, remaining elevated through 72 hours). We interpret this to be due to an inflammatory response to bacterial products (such as lipopolysaccharide) in the heat-killed bacterial inoculum. The phosphate-buffered saline (PBS)-inoculated group exhibited a transient increase of IL-6 message, which indicates that this cytokine is a sensitive marker of the acute response to trauma. Otherwise, PBS invoked only a slight reaction in the mucosa with respect to the other inflammatory mediators being measured.

Acute Disease↗
PubMed1998

Comparative evaluation of culture and PCR for the detection and determination of persistence of bacterial strains and DNAs in the Chinchilla laniger model of otitis media.

This study was designed to determine the persistence of culturable bacteria versus DNA in the presence of a middle ear effusion in a chinchilla model of otitis media. Cohorts of animals were either infected with an ampicillin-resistant Haemophilus influenzae strain or injected with a tripartite inoculum consisting of freeze-thawed Streptococcus pneumoniae; pasteurized Moraxella catarrhalis; and DNA from H influenzae. The H influenzae-infected animals displayed culture positivity and polymerase chain reaction positivity through day 35. In the chinchillas infected with the low-copy number inocula of S pneumoniae, DNA was not detectable after day 1 from the co-inoculated pasteurized M catarrhalis bacteria or the purified H influenzae DNA; however, amplifiable DNA from the live low-copy number bacteria persisted through day 21 even though they were not culture-positive past day 3. These results demonstrate that DNA, and DNA from intact but nonviable bacteria, does not persist in an amplifiable form for more than a day in the presence of an effusion; however, live bacteria, while not culturable, persist in a viable state for weeks.

Ampicillin Resistance↗
PubMed1998

Treatment of chronic suppurative otitis media with topical ciprofloxacin.

To date, only ofloxacin has been approved by the US Food and Drug Administration for treatment of ears with a nonintact tympanic membrane. The purpose of this study was to determine the safety and efficacy of topical ciprofloxacin hydrochloride in the treatment of experimental chronic suppurative otitis media caused by Pseudomonas aeruginosa infection in cynomolgus monkeys. Forty adult cynomolgus monkeys were divided into 4 equal groups, and their ears were challenged with P aeruginosa, drained for 3 weeks, then treated twice daily for 4 weeks with 1 of 4 randomly assigned agents: 1) ciprofloxacin, 2) saline, 3) Cortisporin, or 4) vehicle. The animals were followed up with auditory brain stem response testing, culture, otoscopy, and histopathology. Both ciprofloxacin and Cortisporin treatment resulted in a significantly more rapid rate of clearance of P aeruginosa as compared to treatment with saline (100% versus 20%). Eradication was not associated with resolution of otorrhea after a 4-week period of treatment. There were no significant changes in auditory brain stem response wave latencies for any of the treatment groups. Histopathologic data revealed that there was no statistically significant difference in the amount of outer hair cell loss for the ciprofloxacin group as compared to the control ear and other treatment groups. We conclude, therefore, that topical ciprofloxacin is not ototoxic and is effective in sterilizing the otorrhea, but does not promote resolution of the drainage, in this animal model.

Administration, Topical↗
PubMed1997

Social ties and susceptibility to the common cold.

OBJECTIVE: To examine the hypothesis that diverse ties to friends, family, work, and community are associated with increased host resistance to infection. DESIGN: After reporting the extent of participation in 12 types of social ties (eg, spouse, parent, friend, workmate, member of social group), subjects were given nasal drops containing 1 of 2 rhinoviruses and monitored for the development of a common cold. SETTING: Quarantine. PARTICIPANTS: A total of 276 healthy volunteers, aged 18 to 55 years, neither seropositive for human immunodeficiency virus nor pregnant. OUTCOME MEASURES: Colds (illness in the presence of a verified infection), mucus production, mucociliary clearance function, and amount of viral replication. RESULTS: In response to both viruses, those with more types of social ties were less susceptible to common colds, produced less mucus, were more effective in ciliary clearance of their nasal passages, and shed less virus. These relationships were unaltered by statistical controls for prechallenge virus-specific antibody, virus type, age, sex, season, body mass index, education, and race. Susceptibility to colds decreased in a dose-response manner with increased diversity of the social network. There was an adjusted relative risk of 4.2 comparing persons with fewest (1 to 3) to those with most (6 or more) types of social ties. Although smoking, poor sleep quality, alcohol abstinence, low dietary intake of vitamin C, elevated catecholamine levels, and being introverted were all associated with greater susceptibility to colds, they could only partially account for the relation between social network diversity and incidence of colds. CONCLUSIONS: More diverse social networks were associated with greater resistance to upper respiratory illness.

Adolescent↗
PubMed1997

Maxillary sinus mucosal blood flow during nasal vs tracheal respiration.

OBJECTIVE: To determine the effect of changes from nasal to tracheal respiration on maxillary sinus mucosal blood flow in rabbits with unobstructed sinus ostia. DESIGN: Animals underwent tracheotomy with a T tube and then a small window of intact maxillary sinus mucosa was exposed. Mucosal blood flow was recorded during normal nasal respiration using laser-Doppler velocimetry. At hourly intervals, respiration was changed from the nasal to the tracheal route and then back again. SUBJECTS: Ten anesthetized rabbits were used: 5 underwent single and 4 underwent multiple shifts in the respiratory route, while 1 was monitored continuously during long-term nasal breathing only. RESULTS: A significant decrease in maxillary sinus blood flow occurred on switching from nasal to tracheal respiration and a significant increase in blood flow occurred on return to nasal respiration. Where multiple switches were made, blood flow changes diminished in magnitude, but significant decreases (nasal to tracheal) or increases (tracheal to nasal) were evident in all cases. CONCLUSIONS: It is proposed that the maxillary sinus may act in an accessory capacity to the nose for humidification of inspired air via secretions liberated from the sinus ostium. Furthermore, we suggest that nasal airflow is involved with the reflex regulation of sinus blood flow, probably via stimulation of sensory receptors in the nasal cavity. Reduced maxillary sinus mucosal blood flow may thus contribute to supra-systemic levels of antral carbon dioxide. Since elevated carbon dioxide levels have been shown to reduce maxillary sinus mucociliary activity in vitro, nasal airflow compromise may contribute to the initiation of a cascade of pathophysiological events leading to acute sinusitis.

Animals↗
PubMed1997

Effects of systemic hyperoxia on eustachian tube ventilatory function.

Middle ear negative pressure and effusions, decreased middle ear compliance, and abnormal tympanometry results have been described after diving on oxygen. Middle ear gas hyperoxia has been shown to down-regulate the eustachian tube ventilatory function (ETVF). The purpose of the present study was to investigate to what extent systemic hyperoxia in the face of air-equivalent middle ear gas composition might interfere with the ETVF. ETVF was investigated in four young adult female cynomolgus monkeys by the forced-response and inflation-deflation tests using air while the animals breathed either room air or 100% normobaric oxygen. Higher opening, closing, and steady-state pressures were observed under systemic hyperoxia. The percentage of the applied pressure equalized, and the maximal pressure change on a single swallow in the deflation test were both lower under hyperoxic conditions. The results show that systemic hyperoxia might impair ETVF. This observation adds to our understanding of the pathophysiology of middle ear dysfunction observed after diving on oxygen.

Animals↗