Biomedical subjects

W J Doyle

Publications and source records attributed to W J Doyle.

At least 127 records · Page 7Linked to original sources

PubMed1985

Eustachian tube function in the chinchilla.

Eustachian tube function (ETF) was evaluated in 22 ears of 18 chinchillas using the inflation-deflation and forced-response protocols. The results of the ETF tests showed an unusual function in the chinchilla. Of the 22 tests, one indicated a patulous eustachian tube (ET) and 20 suggested a semipatulous ET. This was evidenced by a passive, pressure-dependent, complete reduction of applied positive or negative ME pressures in these ears. This phenomenon has no counterpart in the ETF of rhesus monkeys or humans. Discrete changes in the continual leakage of applied pressures, indicative of active tubal dilation, were only observed during tests in four ears. Passive tubal resistance was similar to that of humans, though all values were characterized by large variances. Active tubal resistance could only be defined for four of the test ears. The ET of eight ears constricted with swallowing. In nine test ears, neither constriction or dilation was observed during the forced-response test, and four tests showed dilation of the ET with swallowing. These results show that the ETF of the chinchilla is radically different from that of humans or monkeys.

Acoustic Impedance Tests↗

PubMed1985

The role of allergy in the pathogenesis of otitis media with effusion.

To explain an allergic basis for the development of otitis media with effusion (OME), it was suggested that the middle ear mucosa can act as an allergic "shock organ." To evaluate this possibility, 16 juvenile rhesus monkeys were passively sensitized to pollen by intravenous injection of allergic human serum. All ears were then challenged by insufflation of pollen via the nose and eustachian tube (ET), twice daily, for four to five days. Daily tympanometry and otomicroscopy were performed, and on the last day of challenge, tympanocentesis was done to recover effusions. Five animals were killed and the middle ears were processed for histologic study. The results showed that none of the ears developed a middle ear effusion or OME. It is concluded that middle ear challenge with an appropriate pollen antigen in passively sensitized rhesus monkeys does not initiate an inflammatory reaction in the middle ear or induce OME.

Animals↗

PubMed1985

The effects of hypothermia on the latencies of the auditory brain-stem response (ABR) in the rhesus monkey.

The effect of hypothermia on the ABR latencies was evaluated in 14 rhesus monkeys. Data from 6 preliminary experiments showed that middle ear pressure decreased with decreasing body temperature and consequently, all experiments were conducted on animals with tympanostomy tubes inserted to maintain constant middle ear pressure. All animals were sedated with curare and anesthetized with ketamine. Hypothermia was induced by applying ice packs to the animal's body. Rectal temperatures and the ABR to click stimuli were recorded at 3-5 min intervals over a temperature range of from 38 degrees C to 20 degrees C. The pattern of latency change is characterized by increasing latency with decreasing temperature, a greater rate of change for temporally later waves and increasing rate of change for any one wave with decreasing temperature. An exponential function was applied to the data and explained at least 93% of the variances in latency. In general, a single exponential identical for all waves of an animal explained the latency change between 37 and 26 degrees C. Below 26 degrees C, a second and sometimes a third function was required. These findings are similar to those reported previously and to those describing the effect of maturation on the ABR.

Animals↗

PubMed1985

The effects of intranasal histamine challenge on eustachian tube function.

Eustachian tube (ET) function was evaluated bilaterally by use of the inflation-deflation and forced-response test before and after nasal challenge with various doses of histamine in five adult and 10 infant rhesus monkeys (Macaca mulatta). Of the 20 experiments conducted on the infant and juvenile monkeys, functional ET obstruction resulted in six ears after a dose of 0.5 mg of histamine, in 10 ears after a dose of 1 mg, and in four ears after a dose of 2 mg. In contrast, of the 10 experiments conducted on the adult monkeys, functional ET obstruction developed in two ears after a dose of 1 mg of histamine and in two ears after a dose of 4 mg. Six ears failed to respond at doses of 8 mg of histamine. The ET obstruction was characterized by increases in the values of the passive function parameters and an abolition of the ability to equilibrate applied middle ear pressures by muscular activity. ET obstruction was not observed in any ears after challenge with a saline control. The severity of the induced ET obstruction was lessened within 60 minutes after challenge. These data are similar to those reported for intranasal pollen challenges in sensitized rhesus monkeys and human volunteers and suggest that type I allergic reactions at the site of the nasopharyngeal mucosa disrupts the normal functioning of the ET by a mechanism potentially mediated by histamine release.

Acoustic Impedance Tests↗

PubMed1985

Otitis media with effusion in preschool children.

The incidence, prevalence, and natural history of otitis media with effusion (OME) and middle ear high negative pressure (HNP) were investigated in a group of 2 to 6 year old preschool children. The children were examined monthly over a two year period from September 1981 to August 1983. The middle ear status was assessed using a decision-tree algorithm which combined the findings of pneumatic otoscopy, tympanometry, and acoustic reflex measurements. Fifty-three percent of the children in the first year and 61% in the second year developed OME; also during the two years, HNP was documented in 66% of the children. Eighty percent of OME episodes lasted only two months. The prevalence of OME and HNP showed a seasonal variation and a strong association with the presence of upper respiratory infections (URIs). The incidence of OME was independent of age. These data indicate that OME and HNP are prevalent conditions with a high spontaneous recovery in the preschool population.

Audiometry, Pure-Tone↗

PubMed1985

Eustachian tube function in the rhesus monkey model of cleft palate.

Past studies showed that surgical clefting of the palate resulted in impaired active eustachian tube (ET) function and otitis media with effusion (OME) in a Rhesus monkey model. In the present study, this model was used to evaluate the effect of palatal healing on ET function in eight juvenile Rhesus monkeys. Following insertion of bilateral tympanostomy tubes and collection of baseline ET function data, the soft palate was surgically clefted to the right of the midline, and bilateral ET function tests were repeated weekly until the cleft had healed. Results showed that tubal function was severely compromised on the right side but was relatively unaffected on the left side following surgical clefting; active muscular-assisted function was more affected than the passive function; and the abnormal function was reversible with healing of the cleft.

Animals↗

PubMed1985

A comparison of craniofacial growth in normal and cleft palate rhesus monkeys.

In an attempt to better understand the etiology of middle ear disease in humans with cleft palate, a rhesus monkey model was developed. In this study, the model was extended to deal with the specific problem of otitis media in infants with cleft palate. Fifteen rhesus monkeys, Macaca mulatta, were utilized in the present investigation. Soft palate clefts were surgically produced in ten of the subjects, and five served as unoperated controls. Longitudinal data on middle ear status and craniofacial growth were collected until an approximate age of 2 years. Comparisons of linear regression coefficients representing size and rates of growth of craniofacial dimensions were made between operated and control group animals. No significant (p less than .05) differences were found between the groups. It is concluded that surgically produced clefts of the soft palate alter middle ear function and produce ear disease but do not change the rates of growth of the measured components of the craniofacial complex.

Animals↗

PubMed1984

Effect of topical timolol maleate on exercise performance.

The effect of topical timolol maleate on exercise performance was investigated in a randomized double-blind study. Healthy young subjects underwent two graded maximal exercise evaluations on a treadmill. The evaluations were given one week apart. Before each trial, the subjects were given a single drop of either placebo or 0.5% timolol maleate in each eye. The results indicate that topical timolol has a statistically significant effect on both maximal heart rate and time to exhaustion. However, we found that the drug had no effect on the physiologic parameters of Vo2, respiratory rate, Vco2, or respiratory quotient.

Administration, Topical↗

PubMed1984

Eustachian tube obstruction after provocative nasal antigen challenge.

To test if allergic rhinitis is associated with abnormal eustachian tube function (ET), juvenile rhesus monkeys were passively sensitized with serum samples from patients allergic to timothy grass or ragweed pollen. Tympanostomy tubes were inserted for direct measurement of ET function by inflation-deflation and forced-response testing before and after provocative intranasal challenge. Intranasal challenge with pollen (antigen) resulted in rhinorrhea and nasal obstruction. Slight increases in passive ET function values and significantly impaired active ET function were observed after antigen challenge. No changes in nasal airway patency or active ET function resulted from control nonantigen pollen challenges. These data complement our studies in man and support the use of this model to evaluate the relationships among allergic rhinitis, ET function and middle ear disease.

Adult↗

PubMed1984

Antigen-induced eustachian tube obstruction: an intranasal provocative challenge test.

ETO and symptoms of AR have been demonstrated to develop after an intranasal provocative antigen-challenge test. To determine the antigen dose required to produce ETO, intranasal insufflations of increasing amounts of pollen (ragweed or timothy) from 0.1 to 100 mg were delivered to 29 patients, ages 20 to 31 yr with AR who were skin test positive or had elevated serum-IgE antibodies to ragweed or timothy but not pine pollen. Our results demonstrated ETO developed in four ears at 0.05 mg of pollen, in one at 0.5 mg, in four at 1 mg, in 28 at 10 mg, in 15 at 50 mg, and in two at 100 mg of pollen. ETO persisted from 2 to 120 hr. Dose responses and duration of ETO were compared to patients' serum-IgE antibodies that ranged from 3% to 36% B/T (median 26.4%). The patients with the highest serum-IgE antibody values (greater than or equal to 26.4%) required lower antigen-dose challenges (less than or equal to 10 mg) to develop ETO (p less than or equal to 0.01) that also persisted longer (less than or equal to 48 hr) p less than or equal to 0.05. Symptoms of AR developed with an antigen dose that was less than the antigen dose that resulted in the development of ETO in 22 patients and at the same antigen dose in the other seven subjects. At a later date, these same subjects were also challenged intranasally with 50 mg of pine pollen after which no symptoms of AR or development of ETO were noted. In summary, the expression of ETO after provocative intranasal pollen challenge in AR patients is an immune-mediated reaction that is antigen-dose dependent and related to serum-IgE antibody titer.

Adult↗

PubMed1984

Slow negative evoked potentials in the rhesus monkey (Macaca mulatta): myogenic versus neurogenic influences.

The influence of myogenic activity on the generation of slow negative evoked potentials (SN10) to octave, toneburst stimuli (0.5-2 Hz) was investigated in 5 rhesus monkeys (M. mulatta) by comparing responses obtained prior to and during total paralysis induced with curare. The SN10 could be easily elicited during paralysis, regardless of stimulus intensity, rate, or frequency. During paralysis, there were no systematic changes in either response latency or amplitude; variability in latency was less than 10% and changes in response amplitude were within 30%. These findings suggest that the myogenic contribution to the SN10 response is negligible and that this response is of neurogenic origin in the rhesus monkey.

Acoustic Stimulation↗

PubMed1984

Functional eustachian tube obstruction and otitis media in a primate model. A review.

In most infants and children with chronic otitis media with effusion, an inability to dilate the Eustachian tube actively has been documented. This functional tubal obstruction has been suggested to underlie the development of the disease. To test this possibility a variety of models using the Rhesus monkey were developed. The normal tubal dilatory system was impaired, resulting in sterile otitis media with effusion. The duration and nature of the disease was shown to be dependent on the severity and duration of the impairment in tubal function. These studies support the causative role of functional Eustachian tube obstruction in the development of otitis media with effusion and provide a series of models in which to study the etiology, pathogenesis, sequelae and complications as well as the treatment and preventions of the pathology in an animal species physiologically and anatomically similar to man.

Animals↗

PubMed1983

Effect of levator veli palatini muscle excision on eustachian tube function.

The role of the levator veli palatini (LVP) muscle in eustachian tube (ET) physiology was investigated in five juvenile rhesus monkeys (Macaca mulatta). The baseline ET function and middle ear pressures were documented longitudinally for a period of six months prior to bilateral excision of the LVP muscle, and postoperative ET function and middle ear status were assessed for a period of five months. During the postoperative follow-up period, otitis media with effusion was not observed and middle ear pressure values remained within the normal baseline values. Parameters of ET function as measured by the forced-response test did not show any significant differences in comparison with baseline values. These findings provide additional evidence that the operational biomechanics of the ET are independent of the integrity of the LVP muscle, and that the tensor veli palatini is the only paratubal muscle responsible for normal active opening of the ET.

Animals↗

PubMed1983

Treatment of ampicillin-resistant acute otitis media in the chinchilla.

The efficacy of sulbactam sodium (CP45,899-2) was investigated using the chinchilla animal model of acute otitis media with effusion (AOME). Both ears of 78 chinchillas were inoculated with beta-lactamase-producing nontypable Hemophilus influenzae. Half of the animals were treated with ampicillin sodium alone (group A) and the remaining animals received ampicillin plus sulbactam (group B). On day 14, all of the ears in group B were culture-negative whereas H influenzae was recoverable in over 70% of the effusions in group A. Similarly, the course of middle ear effusion was significantly abbreviated in group B during the two-week study period. These findings suggest that sulbactam in combination with ampicillin is effective in treating AOME secondary to infection with beta-lactamase-producing nontypable H influenzae in the chinchilla animal model.

Acute Disease↗

PubMed1983

Maturation of the auditory brain stem response in rhesus monkeys (Macaca mulatta).

To document the maturational changes in the auditory brain stem response (ABR) of the rhesus monkey, longitudinal and cross-sectional data were collected on a panel of 31 animals during the first year of life. Each ABR test consisted of averaging 2048 responses to click stimuli delivered at a rate of 21 clicks/sec and elicited at 60, 40, 20 and 10 dB HL intensities in accordance with procedures described previously. The morphology of the ABR wave form recorded at birth was similar to that at 12 months of age and the latencies of the component waves decreased exponentially over this period. The magnitude of decrease in latency was greatest for wave IV and least for wave I. The regression lines for the log of the latencies of 3 waves on age were computed for 3 animals followed longitudinally and for the cross-sectional data set. The slopes of these regression lines were different among animals, indicating differing rates of maturation. However, these slopes were identical for the component waves of any one animal, suggesting that the rate of maturation was constant over the auditory pathway. These changes were similar in pattern to those reported for human data and suggest that the rhesus monkey may serve as an appropriate model of auditory development in man.

Animals↗

PubMed1983

Immunologic-mediated eustachian tube obstruction: a double-blind crossover study.

Eight subjects with seasonal allergic rhinitis confirmed by positive skin tests and serum radioallergosorbent test to ragweed or timothy grass pollen were identified. A double-blind provocative antigen challenge was performed with intranasal insufflation of 50 mg of dry pollen to which the subject was either sensitive (ragweed or timothy) or not sensitive (pine). Before and after pollen insufflation, measurements of nasal function by nasal rhinomanometry and eustachian tube (ET) function by the nine-step tympanometry test were performed for up to 14 days. The ability to dilate the ET was documented in 14 of the 16 ears of the eight subjects before challenge. Within 30 min after antigen challenge transient obstruction of the ET associated with inability to dilate upon swallowing was observed in all 14 ears. Clinical symptoms of allergic rhinitis, including rhinorrhea and nasal obstruction, were produced in all subjects. ET function changes were reversible in three of 14 ears within 2 hr but persisted for more than 3 days in six of the ears. As a control, insufflation of pine pollen did not alter ET function or rhinomanometric values or produce clinical symptoms in the eight subjects. These findings suggest an allergic basis for ET obstruction and possibly for the development of otitis media with effusion.

Adolescent↗

PubMed1983

The anatomy of the auditory tube and paratubal musculature in a one month old cleft palate infant.

The auditory tube, middle and inner ear, and paratubal musculature were removed en bloc at autopsy from a 1 month old white cleft palate female. The specimen was serially sectioned in a coronal plane and studied under light microscopy. Severe inflammatory changes were observed in the middle ear and osseous portion of the auditory tube in association with the presence of a middle ear effusion. While the posterior tubal lumen, tubal cartilage, and tensor veli palatini (TVP) and tensor tympani muscles were similar to those of an age-matched control specimen, the anterior tubal lumen was seen to be superoinferiorly abbreviated with a large intrusive malpositioned levator veli palatini (LVP) muscle occupying the inferior tubal floor. This muscle was noted to divide into two bundles on proceeding posteriorly with the more superior bundle taking an abnormal origin from the inferior surface of the tube. The luminal compression observed in this specimen is reminiscent of that previously described in cleft fetuses though the abnormal morphology of the LVP muscle has not been reported for the few cleft palate specimens studied. It is probable that this morphology is idiomatic to the present specimen and not a characteristic of the cleft palate condition.

Cleft Lip↗

PubMed1982

Acquired subglottic stenosis following prolonged endotracheal intubation. A canine model.

We developed a canine animal model of subglottic stenosis following prolonged intubation with modified non-cuffed endotracheal tubes. None of the puppies intubated for seven days had an irreversible stenosing subglottic lesion, whereas all animals intubated for 14 days or more had at least a 40% to 50% reduction of the subglottic lumen secondary to maturing fibrotic stenosis. The model described is more congruent with the known and suspected pathogenesis in those infants and children who require prolonged endotracheal intubation and subsequently acquire subglottic stenosis, and can be used in evaluating the efficacy of medical therapy or surgical therapy, or both, in the prevention or management of this disease.

Animals↗