Effects of chronic peanut consumption on energy balance and hedonics.

OBJECTIVE: To investigate the effects of chronic peanut consumption on energy balance and hedonics. DESIGN: Thirty-week, cross-over, intervention study. Participants were provided 2113+/-494 kJ/day (505+/-118 kcal/day) as peanuts for 8 weeks with no dietary guidance (free feeding-FF), 3 weeks with instructions to add peanuts to their customary diet (addition-ADD) and 8 weeks where peanuts replaced an equal amount of other fats in the diet (substitution-SUB). SUBJECTS: Fifteen, healthy, normal-weight (BMI of 23.3+/-1.8) adults, aged 33+/-9 y. MEASUREMENTS: Dietary intake, appetitive indices, energy expenditure, body weight and hedonics. RESULTS: During FF, peanut consumption elicited a strong compensatory dietary response (ie subjects compensated for 66% of the energy provided by the nuts) and body weight gain (1.0 kg) was significantly lower than predicted (3.6 kg; P<0.01). When customary dietary fat was replaced with the energy from peanuts, energy intake, as well as body weight, were maintained precisely. Participants were unaware that body weight was a research focus. Resting energy expenditure was increased by 11% after regular peanut consumption for 19 weeks (P<0.01). Chronic consumption of peanuts did not lead to a decline in pleasantness or hunger ratings for peanuts nor did it lead to any hedonic shift for selected snack foods with other taste qualities during any of the three treatments. CONCLUSIONS: Despite being energy dense, peanuts have a high satiety value and chronic ingestion evokes strong dietary compensation and little change in energy balance.

Prevention of otitis media with effusion by repeated air inflation in a monkey model.

OBJECTIVES: To test the following hypotheses that (1) middle ear (ME) air inflation prevents the development of otitis media with effusion in a monkey model of functional eustachian tube obstruction, and (2) ME inflation treatment of otitis media with effusion can cause artifactual clinical improvements due to fluid displacement from the tympanum to the adjacent airspaces. DESIGN: Randomized controlled trial. SUBJECTS: Twelve cynomolgus monkeys. INTERVENTIONS: Eustachian tube dysfunction was induced by botulinum paralysis of the right tensor veli palatini muscle in all monkeys. Before and on study days 9, 15, and 21 after paralysis, the presence or absence, and distribution of ME effusion were documented using magnetic resonance imaging (MRI). Right and left ears were examined twice daily for 21 days using tympanometry, and right ME air inflation (n = 6 ears) or sham inflation (n = 6 ears) was done immediately after those examinations if the ME pressure was -100 mm H2O or less. On 10 of the scheduled MRI evaluations, the MRI was repeated immediately after an inflation to document the possible redistribution of fluid within the ME caused by the maneuver. RESULTS: Middle ear pressure remained within normal limits for the follow-up period in 11 of the 12 nonparalyzed left ears, in none of the 6 sham-inflated right ears, and in 3 of the 6 air-inflated right ears. Three air-inflated right ears developed flat tympanograms (ie, days 14 through 16). Magnetic resonance imaging documented inflammation and fluid in 1 of the 11 nonparalyzed left ears and in all sham-inflated right ears. Lesser degrees of inflammation and effusion based on MRI evaluations were noted for the 3 air-inflated right ears that retained near-ambient pressures when compared with the right 3 ears that developed a flat tympanogram. The MRI measure of effusion quantity within the tympanum was decreased acutely after inflation, but was simultaneously increased in the adjacent airspaces of the temporal bone. CONCLUSIONS: Repeated air inflation prevented the development of otitis media with effusion in 50% of the ears with functional eustachian tube obstruction. Postinflation MRI documented the displacement of fluid by inflation from the tympanum to the mastoid and petrous air cells. Using standard clinical evaluations such as tympanometry and otoscopy, this fluid redistribution can cause a false diagnosis of improvement.

The effects of changing middle ear pressure and gas partial pressure on mucosal blood flow and vascular permeability in the chinchilla.

OBJECTIVE: To determine if middle ear (ME) gas composition and/or total pressure regulates local mucosal blood flow (MBF) and vascular permeability. The hypotheses tested are: (1) relatively high local CO2 tensions and/or low O2 tensions increase the ME MBF and vascular permeability; and (2) sub-atmospheric total ME pressure provokes similar effects. METHODS: The responses of ME MBF and vascular permeability parameters were measured during 60 min exposures of chinchilla MEs to one of two test gas mixtures (16.3% O2, 5.1% CO2, balance N2, or 5.3% O2, 15.6% CO2, balance N2) applied at different levels of underpressure (ref. ambient). In the first set of experiments (n = 19), mucosal perfusion parameters were recorded using a Laser Doppler Flowmeter for 60 min before and 60 min after exposure to the experimental conditions. In the second set of experiments (n = 19 chinchillas, 38 ears), the MEs were exposed to the gas mixtures and then maintained for 60 min at ambient pressure or at negative pressures of -200, -400, -600 mmH2O. Fifty minutes into the experiment, the animals were injected intravenously with 60 mg/kg of horseradish peroxidase (HRP). The animals were killed and existing effusion was aspirated, its volume recorded and then analyzed for total protein. From surface preparations of the ME mucosa, vascular leakage sites were measured as percent total surface area using an image analysis program with the threshold window set to discriminate HRP stain. RESULTS: Throughout the 120 min in the first set of experiments, the measured MBF parameters decreased in all exposure groups. Comparisons among groups for the absolute magnitude of the change from baseline showed that high local CO2 partial pressures decreased MBF and ME underpressures increased MBF, but the effects did not achieve statistical significance. The results of the second set of experiments demonstrated no effect of gas composition on any of the measured parameters of vascular permeability. All measures of permeability were linearly related to the magnitude of the underpressure. CONCLUSION: These data support a role for total ME pressure, but not CO2 partial pressure in regulating ME MBF and vascular permeability.

Treatment of chronic suppurative otitis media with topical tobramycin and dexamethasone.

OBJECTIVES: To investigate the safety and efficacy of a topical combination of tobramycin and dexamethasone in a primate model of chronic suppurative otitis media (CSOM) and to explore the contribution of the added topical steroid for the treatment of CSOM. DESIGN: Blinded, randomized, placebo-controlled trial. SUBJECTS: Sixty juvenile cynomolgus monkeys randomized into the following 6 treatment groups of 10 monkeys each: 0.3% tobramycin (group 1), combined 0.3% tobramycin-0.1% dexamethasone (group 2), combined 1.0% tobramycin-0.33% dexamethasone (group 3), 0.1% dexamethasone (group 4), vehicle (group 5), and phosphate-buffered saline solution (group 6). INTERVENTIONS: Chronic suppurative otitis media was established by inoculating the right ear with Pseudomonas aeruginosa. After 4 weeks of drainage, animals were treated according to the group assignment with 3 drops twice daily for 7 weeks. Hearing thresholds were monitored with repeated auditory brainstem response testing (ABR), and clinical response was monitored with repeated otoscopic examinations and cultures throughout the study. Cytocochleograms were evaluated for quantification of outer hair cell loss. RESULTS: Rapid resolution of otorrhea and eradication of P aeruginosa occurred in all groups receiving tobramycin. The inclusion of dexamethasone accelerated the resolution of otorrhea and negative yields of cultures compared with tobramycin alone. Otorrhea and positive culture findings persisted in the groups not treated with topical antibiotic. Results of ABRs at 4 and 8 weeks and cytocochleograms for outer cell hair loss were not affected by drug administration. Perilymph samples collected at the end of the study showed no detectable tobramycin. CONCLUSIONS: Combined tobramycin-dexamethasone ear drops were safe and effective in the monkey CSOM model. Dexamethasone enhanced the efficacy of tobramycin.

Validation by magnetic resonance imaging of tympanometry for diagnosing middle ear effusion.

This study was performed to correlate tympanometric gradient with measurements of effusion quantity by use of MRI during an experimental otitis media with effusion episode in 4 cynomolgus monkeys. Paired results for the intensity values of the T(2)-weighted MRI scans and the tympanometric width measured in the right ear of all animals before and on days 15, 21, 29, and 36 after botulinum paralysis of the tensor veli palatini muscle were analyzed. All right ears showed a progressive increase during the study period in the signal intensity of the MRI. Whereas the average middle ear pressures decreased, the average tympanometric widths demonstrated a progressive increase during the course of the experimental otitis media with effusion. Significant correlations between tympanometric width and MRI measures of effusion were documented, confirming the high predictive value of the tympanometric width for diagnosing the presence and quantity of middle ear effusion.

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.

Middle ear inflation for diagnosis and treatment of otitis media with effusion.

An adult (18 years), healthy, male subject with persistent bilateral middle ear (ME) underpressure and a history of recurrent otitis media into his teen years was identified. The response of his MEs to air inflation was evaluated and showed an immediate pressure increase after a Valsalva maneuver followed by a rapid pressure drop to approach the pre-inflation levels. That response is consistent with the presence of ME effusion, which was not diagnosed by otoendoscopy or tympanometry, but was visualized bilaterally within the mastoid regions using magnetic resonance imaging (MRI). The patient was treated for 25 days with ME inflation (3/day) and then re-examined. On each treatment day, he recorded his ME pressure using tympanometry before and after one inflation maneuver. The patient's compliance with the treatment protocol was high, and successful gas transfers were documented on most days. Over the course of treatment, pre-inflation ME pressure became more normal bilaterally. When compared to the pre-treatment test, the post-treatment inflation test showed a similar rate of ME pressure decrease, but significantly higher terminal pressures. On follow-up but not during the pre-treatment period, discrete changes in ME pressure attributable to ET openings were noted during test sessions. MRI documented lesser amounts of effusion in the mastoid, but not complete disease resolution. The significance of these observations to the design of a well controlled clinical trail of ME inflation as a treatment for otitis media is discussed.

Higher rates of pressure decrease in inflamed compared with noninflamed middle ears.

Recent clinical trials have renewed interest in middle ear inflation as a treatment for otitis media with effusion. However, air inflation in human beings with significant negative middle ear pressures was shown to be followed by a rapid pressure decrease to approach the preinflation values. In this experiment, the middle ears of anesthetized rhesus monkeys with unilateral inflammation were inflated at different times with air or N2, and pressures were recorded by tympanometry until they had stabilized or the animal had recovered from anesthesia. The results for air inflations reproduced those reported for human beings with negative pressures. Similarly, after N2 inflation a significantly greater rate of pressure decrease and significantly lesser terminal pressures were observed for inflamed ears when compared with the contralateral control ears. However, the rate of pressure decrease and the magnitude of the pressure drop were dampened by sequential N2 inflations. These observations have clinical implications with respect to the efficacy of inflation as a treatment for otitis media with effusion.

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.

Trans-mucosal inert gas exchange constants for the monkey middle ear.

OBJECTIVE: The purpose of the study was to estimate the exchange constants for Argon and N2 across the middle ear mucosa of monkeys for use in mathematical models of middle ear pressure regulation. METHODS: In five anesthetized monkeys, the tympanic membrane was perforated and, with the animal breathing room air, a 13-ml probe attached to an Argon gas source and to a pressure transducer was introduced into the ear canal and sealed. The probe and middle ear volume was washed with Argon and then closed to the gas source. Gas samples were withdrawn from the probe at 15-min intervals for composition analysis using an online mass spectrometer. Probe partial pressures of Argon and N2 were regressed on time and the slopes of those functions were divided by the respective average partial pressure gradient for the interval to estimate the exchange constants. RESULTS: The average trans-mucosal exchange constants for Argon and N2 were 0.0007 +/- 0.0001 and 0.0003 +/- 0.0001/min, respectively. The average ratio of the two constants was 2.60 +/- 0.36 which is not different from the value of 2.3 predicted for perfusion limited gas exchange. CONCLUSION: These results confirm a very slow, perfusion limited trans-mucosal exchange of N2 and other inert gases across the middle ear mucosa. They infer that the required frequency of Eustachian tube openings to prevent the development of middle ear effusion is low and on the order of one/day.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Magnetic resonance imaging of the development of otitis media with effusion caused by functional obstruction of the eustachian tube.

In this study, magnetic resonance imaging (MRI) was used to define in vivo the effect of experimental functional obstruction of the eustachian tube (ET) on vascular permeability and the development of middle ear (ME) effusion. After collection of baseline data for ME pressure and MRI, the right tensor veli palatini muscle of 10 cynomolgus monkeys was injected with botulinum toxin A to induce ET obstruction. The left tensor veli palatini muscle was injected with saline in 4 monkeys. Right and left ME pressures and compliances were measured twice daily over a follow-up period of 36 days, and MRI scanning sessions including administration of a contrast agent, gadopentetate dimeglumine, were repeated on days 3, 6, 11, 15, 21, 29, and 36 in 6 animals and on days 15, 21, 29, and 36 in 4 animals. Two right ears did not develop underpressures, 5 developed persistent underpressures, and 3 developed underpressures that resolved. No changes in MRI parameters were noted for the ears that did not develop underpressures, but a progressive brightening of the ME on T2-weighted images, indicative of the development of inflammation and effusion, was noted for the others. Also, an increasing rate of transfer of the contrast agent between the vascular and ME compartments, indicative of increasing vascular permeability, was observed to track the temporal changes in ME pressure. These results support a causal relationship between ET dysfunction, ME underpressures, increased vascular permeability, and otitis media with effusion