Control Ears Research Articles

A rabbit model for assessment of volatile metabolite changes observed from skin: a pressure ulcer case study

Human skin presents a large, easily accessible matrix that is potentially useful for diagnostic applications based on whole body metabolite changes—some of which will be volatile and detected using minimally invasive tools. Unfortunately, identifying skin biomarkers that can be reliably linked to a particular condition is challenging due to a large variability of genetics, dietary intake, and environmental exposures within human populations. This leads to a paucity of clinically validated volatile skin biomarker compounds. Animal models present a very convenient and attractive way to circumvent many of the variability issues. The rabbit (Leporidae) is a potentially logistically useful model to study the skin metabolome, but very limited knowledge of its skin metabolites exists. Here we present the first comprehensive assessment of the volatile fraction of rabbit skin metabolites using polydimethylsiloxane sorbent patch sampling in conjunction with gas chromatography/mass spectrometry. A collection of compounds that are secreted from rabbit skin was documented, and predominantly acyclic long-chain alkyls and alcohols were detected. We then utilized this animal model to study differences between intact skin and skin with early pressure ulcers, as the latter are a major problem in intensive care units. Four New Zealand female white rabbits underwent ulcer formation on one ear with the other ear as a control. Early-stage ulcers were created with neodymium magnets. Histologic analysis showed acute heterophilic dermatitis, edema, and micro-hemorrhage on the ulcerated ears with normal findings on the control ears. The metabolomic analysis revealed subtle but noticeable differences, with several compounds associated with the oxidative stress-related degradation of lipids found to be present in greater abundances in ulcerated ears. The metabolomic findings correlate with histologic evidence of early-stage ulcers. We postulate that the Leporidae model recapitulated the vascular changes associated with ulcer formation. This study illustrates the potential usefulness of the Leporidae model for skin metabolome studies. Additionally, skin metabolome analysis may enhance an understanding of non-skin sources such as urine or breath.

Can floseal\u2122 be applied safely during otologic surgery? Assessment of ototoxicity in a chinchilla animal model

BackgroundIn otologic surgery good visualization is paramount, and patients with bleeding diatheses or who need to be anti-coagulated can present a significant challenge. Here, we determine whether Floseal™, a hemostatic matrix, is ototoxic in a validated animal model.MethodsNine chinchillas housed in the animal care facilities of the Montreal Children’s Hospital Research Institute were used for the study. After a myringotomy incision was made in each tympanic membrane, baseline auditory brainstem response measurements were performed at 8, 20, and 25 kHz. In each animal one ear was randomized to receive Floseal™ to the middle ear cavity, whereas the other ear served as the control and received 0.9% sodium chloride. Outcome measures included early (day 7) and late (day 30) auditory brainstem response, clinical evidence of facial nerve or vestibular disturbance and histological evidence of ototoxity.ResultsThere was no significant hearing threshold shift on auditory brainstem response across all tested frequencies for both experimental and control ear. No animals receiving Floseal™ developed facial or vestibular nerve dysfunction and there was no histological evidence of ototoxicity.ConclusionBased on the preliminary ototoxicity assessment on nine chinchillas, transtympanic Floseal™ does not appear to be ototoxic. More studies are warranted to assess the safety and applicability of the product in humans.

Safety of transtympanic application of probiotics in a chinchilla animal model

BackgroundChronic suppurative otitis media can be recalcitrant and difficult to treat, particularly with the increasing occurrence of antibiotic resistance. Lactobacillus plantarum is a probiotic that has been shown to decrease S. aureus and P. aeruginosa growth in wounds, making it a good candidate for the treatment of chronic suppurative otitis media. However, before it can be applied in the ear, its ototoxicity potential must be evaluated.MethodsA prospective controlled trial was conducted in a chinchilla animal model at the Animal care research facilities of the Montreal Children’s Hospital Research Institute to determine whether Lactobacillus plantarum is ototoxic when applied transtympanically. Ten chinchillas each had one ear randomly assigned to receive 109 CFU/mL of Lactobacillus plantarum solution, while the contralateral ear received saline. Auditory brainstem responses were measured bilaterally at 8, 20, 25 kHz before, at 7–10 days after application, and at 28 days after application of probiotic or saline. Facial nerve and vestibular function were assessed clinically.ResultsThere were no statistically significant differences in hearing thresholds between control and experimental ears at 28 days after application. A difference of 11 dB was noted in the 25 kHz range at day 7–10, but resolved by day 28. No animals receiving probiotics developed vestibular nerve dysfunction. There was no histologic evidence of auditory hair cell damaged evidenced by scanning electron microscopy.ConclusionOur study suggests that a single application of Lactobacillus plantarum at 109 CFU/mL does not cause ototoxicity in a chinchilla animal model. These preliminary safety evaluations and the pathogen inhibitory effects of L. plantarum demonstrated by previous studies present this probiotic as a candidate of interest for further investigation.

Aminoglycoside Increases Permeability of Osseous Spiral Laminae of Cochlea by Interrupting MMP-2 and MMP-9 Balance.

The spiral ganglion neurons (SGNs) located in the Rosenthal's canal of cochlea are essential target for cochlear implant. Previous studies found that the canaliculi perforantes, small pores on the surface of the osseous spiral lamina (OSL) of the scala tympanic (ST) of cochlea, may provide communication between the cochlear perilymph and SGNs. In this study, we found that chronic treatment of aminoglycosides antibiotics, which is well known to cause sensory cell damage in the cochlea, induced significant damage of bone lining cells on the OSLs and increased the permeability of the Rosenthal's canal. The pores among the bone lining cells became significantly wider after chronic treatment of amikacin (100mg/kg/day for 3-7days). Injection of Evans Blue in the ST resulted in significant increase in its migration in the modulus in the amikacin-treated cochlea compared to the control ears, suggesting increased permeability of these passages. Treatment of amikacin with oxytetracycline, an inhibitor of matrix metalloproteases (MMPs), significantly reduced the amount of dye migrated from the ST to the modiolus. These results suggest that amikacin enhanced the permeability between the ST and SGNs by increasing MMPs. Aggregating the permeability of the bone lining cells on the OSLs may benefit gene and stem cell delivery to the SGNs in the cochlea.

L-Asparaginase-Induced Allergy in Mice: Effects of Concomitant Drugs and Anti-IgE Antibody

BACKGROUND: L-Asparaginase (L-Asp) derived from E. coliis one of the essential drugs for the treatment of acute lymphoblastic leukemia (ALL) and lymphoma. Native L-Asp often causes hypersensitivity reactions, including anaphylaxis, which account for termination and inferior outcome of L-Asp therapy of ALL. Since the characteristics of L-Asp-induced hypersensitivity are not well documented, there is neither suitable treatment for hypersensitivity to L-Asp nor animal model of L-Asp allergy. In addition, some anti-cancer drugs, used concomitantly with L-Asp, affect lymphocyte activities, the role of such drugs on L-Asp hypersensitivity is not known.Aims:In this study, we induced type I hypersensitivity to E. coliL-Asp in mice in order to investigate the mechanism and treatment of L-Asp allergy. Anti-IgE antibody, binding to Fc region of IgE to block the binding to FcεRI receptor, was used as a candidate for the treatment of L-Asp hypersensitivity. Furthermore, we examined the effects of methotrexate (MTX) and cyclophosphamide (CY). which reportedly impair the functions of Th17 and Treg cells, respectively.Methods: Male BALB/c mice (7 week old) were intraperitoneally injected L-Asp (10, 20, 100 IU/mouse) with Al (OH)3gel on days 0 and 14. The right ears of the mice were locally sensitized on days 17, 20, 23 by intradermal injection of L-Asp (1, 2, 10 IU/mouse). Antigen challenge was carried out on day 26 by intradermal injection of L-Asp. MTX (50, 100, 200 mg/kg) and CY (150 mg/kg) were intraperitoneally administrated on day -2 and day 12. On day 25, either anti-IgE antibody (50, 100 mg/mouse) or control IgG was intraperitoneally administered to the sensitized mice. The ear thickness was measured (n=6 or more). H&E and toluidine blue stainings of ear sections were performed.Results: L-Asp challenge immediately induced ear edema, in a dose-dependent manner. The reaction reached to a peak at 1 hr after stimulation (dosage: sensitization = 100 IU/mouse, challenge = 10 IU/mouse; edema thickness: 31.25±3.8 μm vs control 4.38±1.9 μm, p<0.01), which subsided within 24 hr. Microscopic observations showed eosonophil infiltration (H&E staining; 0.5±0.2 cells/HPF in control ears and 10.4±1.0 cells/HPF in challenged ears, P<0.001) and degranulation of mast cells (toluidine blue staining; 8.4±0.9 % in control ears and 47.6±5.8 % in challenged ear, P<0.001). Anti-IgE antibody significantly inhibited the ear swelling to 7.3±1.2 μm (P<0.01) as well as microscopic changes in eosinophil infiltration and mast cell degranulation. When the mice were treated with anticancer drugs prior to sensitization, the ear swellings were augmented by CY (43.54±4.0 μm, P<0.05) but not MTX (31.67±5.5 μm, not significant). Anti-IgE antibody also inhibited CY-augmented ear swelling.Conclusions: From these results, we firstly established animal model for type I hypersensitivity to L-Asp. Using this model, we conclude that non-anaphylactogenic neutralizing antibody of IgE, such as omalizumab, can be a candidate drug for the treatment of L-Asp hypersensitivity. Also, CY-induced suppression of Treg function may enhance Th2 responses so as to augment L-Asp hypersensitivity. Further investigations for the detection and avoidance of L-Asp hypersensitivity are under the way. DisclosuresNo relevant conflicts of interest to declare.

Potential of using host plant resistance, nitrogen and phosphorus fertilizers for reduction of Aspergillus flavus colonization and aflatoxin accumulation in maize in Tanzania

Aflatoxin contamination (AC) in maize, caused by the fungal pathogen Aspergillus flavus (Link), starts at pre-harvest stage. Hence, interventions that reduce entry and development of A. flavus in the field are required. Trials were carried out at Seatondale and Igeri, to evaluate the effects of nitrogen and phosphorus fertilizer combinations, hereafter referred to as fertilizers, on A. flavus and AC in maize kernels. The main treatments were four combinations of N and P fertilizers (60 or 120 kg Nha−1 with 15 or 30 kg Pha−1) and sub-treatments were of six popular maize hybrids. Plants at 50% silking were inoculated with the fungus through the silk channels. Grains from inoculated and control ears were analysed for AC using Enzyme Linked Immunosorbent Assay, and pathogen content quantified by Quantitative Polymerase Chain reaction. Higher AC (mean 6.51 μg kg−1) occurred at Seatondale than Igeri (mean 0.45 μg kg−1), probably due to low temperatures (8–23 °C) at Igeri. Fertilizers didn't cause significant differences in neither pathogen colonization nor AC at both sites. However, mean A. flavus accumulation, as measured by pathogen host DNA ratio, was thrice (0.16) as high in sub-optimal fertilizer conditions compared to optimal fertilizer rate (0.05). All hybrids were susceptible to A. flavus and AC, though a difference in AC was noted among the hybrids at both sites. PAN 691 showed the highest AC (14.68 μg kg−1), whereas UHS 5210 had the lowest AC (1.87 μg kg−1). The susceptibility varied among the hybrids and was mostly associated with ear droopiness, husk tightness, days to 50% silking, 50% pollen shed, Anthesis to silking interval, diseased ears, insect damaged ears, kernel texture, dry matter, grain filling, ear height, kernel ash content and kernel moisture content. At Seatondale, A. flavus accumulation was positively correlated with aflatoxin (r = 0.606), and both A. flavus accumulation and AC were positively correlated with diseased ears. Selection and growing of less susceptible varieties under optimal fertilizer regime offer ideal strategy for sustainable reduction of A. flavus and aflatoxin contamination in maize at pre-harvest.

Outcomes of Bone Anchored Hearing Aids (BAHA) for Single Sided Deafness in Nontraditional Candidates.

To assess both quality of life (QOL) and hearing outcomes in bone anchored hearing aid (BAHA) users for single sided deafness with 1) less than total hearing loss in the deaf ear, or 2) some degree of hearing loss in the better ear and compare them to traditional candidates. Prospective comparative cohort study. Tertiary referral center. Patients with a BAHA for single sided deafness were assigned into groups based on hearing thresholds in the deaf ear (> or <90 dBHL) and the control ear (> or <25 dBHL). A panel of QOL measures (GBI, HUI Mark 3, and the Outer EAR) and a prospective assessment of hearing including Quick SIN and HINT in quiet and noise, and a localization task. Differences in QOL, hearing performance in noise, and localization ability. Nineteen patients were tested. Patients with residual hearing in the BAHA ear showed nonsignificant trends toward improved performance in noise localization compared with those without residual hearing. There were no statistically significant differences in QOL between groups. Patients with hearing loss in the control ear had equivalent QOL scores to those with normal hearing in the control ear despite performing worse on speech in noise tasks. BAHA patients with hearing loss in the better ear seem to perform worse in noise relative to those without but have equivalent perceived benefit. Residual hearing in the implanted ear may improve performance. A larger sample size is needed to confirm these trends.

Applying Neurotrophins to the Round Window Rescues Auditory Function and Reduces Inner Hair Cell Synaptopathy After Noise-induced Hearing Loss.

Applying neurotrophins to the round window immediately after a single noise exposure will prevent noise-induced hidden hearing loss. Loud noise can eliminate neural connections between inner hair cells and their afferent neurons (thereby diminishing sound perception) without causing a detectable change on audiogram. This phenomenon is termed hidden hearing loss. Guinea pigs were exposed for 2 hours to 4 to 8 kHz noise at either 95 or 105 dB SPL. Immediately afterward a 4 μl bolus of neurotrophins (brain-derived neurotrophic factor 1 μg/μl, and neurotrophin-3 1 μg/μl) was delivered to the round window of one ear, and saline to the other. Auditory brainstem responses to pure-tone pips were acquired preoperatively, and at 1 and 2 weeks' postexposure. Cochleae were removed and whole mounted for immunohistochemical analysis, with presynaptic ribbons of inner hair cells and associated postsynaptic glutamatergic AMPA receptors identified using CtBP2 and GluA2 antibodies respectively. After exposure to 105 dB noise, threshold did not change, but the amplitude growth of the auditory brainstem response was significantly reduced in control ears in response to 16 and 32 kHz tones. The amplitude growth was also reduced neurotrophin ears, but to a lesser degree and the reduction was not significant. Similar results were obtained from control ears exposed to 95 dB, but amplitude growth recovered in neurotrophin-treated ears, this reaching statistical significance in response to 16 kHz tones. There were significantly more presynaptic ribbons, postsynaptic glutamate receptors, and colocalized ribbons after neurotrophin treatment. A single dose of neurotrophins delivered to the round window reduced synaptopathy and recovered high-frequency hearing in ears exposed to 95 dB noise. These findings suggest that hidden hearing loss may be reduced by providing trophic support to the cochlea after injury.

Rhamnolipid Biosurfactant against Fusarium verticillioides to Control Stalk and Ear Rot Disease of Maize.

Antifungal activity of rhamnolipids (RLs) has been widely studied against many plant pathogenic fungi, but not against Fusarium verticillioides, a major pathogen of maize (Zea mays L.). F. verticillioides causes stalk and ear rot of maize or asymptomatically colonizes the plant and ears resulting in moderate to heavy crop loss throughout the world. F. verticillioides produces fumonisin mycotoxins, reported carcinogens, which makes the contaminated ears unsuitable for consumption. In this study, the RL produced using glucose as sole carbon source was characterized by FTIR and LCMS analyses and its antifungal activity against F. verticillioides was evaluated in vitro on maize stalks and seeds. Further, the effect of RL on the mycelia of F. verticillioides was investigated by scanning electron microscopy which revealed visible damage to the mycelial structure as compared to control samples. In planta, treatment of maize seeds with a RL concentration of 50 mg l-1 resulted in improved biomass and fruiting compared to those of healthy control plants and complete suppression of characteristic disease symptoms and colonization of maize by F. verticillioides. The study highlights the potential of RLs to be used for an effective biocontrol strategy against colonization of maize plant by F. verticillioides.

Time course and frequency specificity of sub-cortical plasticity in adults following acute unilateral deprivation

Auditory deprivation and stimulation can change the threshold of the acoustic reflex, but the mechanisms underlying these changes remain largely unknown. In order to elucidate the mechanism, we sought to characterize the time-course as well as the frequency specificity of changes in acoustic reflex thresholds (ARTs). In addition, we compared ipsilateral and contralateral measurements because the pattern of findings may shed light on the anatomical location of the change in neural gain. Twenty-four normal-hearing adults wore an earplug continuously in one ear for six days. We measured ipsilateral and contralateral ARTs in both ears on six occasions (baseline, after 2, 4 and 6 days of earplug use, and 4 and 24 h after earplug removal), using pure tones at 0.5, 1, 2 and 4 kHz and a broadband noise stimulus, and an experimenter-blinded design. We found that ipsi- as well as contralateral ARTs were obtained at a lower sound pressure level after earplug use, but only when the reflex was elicited by stimulating the treatment ear. Changes in contralateral ARTs were not the same as changes in ipsilateral ARTs when the stimulus was presented to the control ear. Changes in ARTs were present after 2 days of earplug use, and reached statistical significance after 4 days, when the ipsilateral and contralateral ARTs were measured in the treatment ear. The greatest changes in ARTs occurred at 2 and 4 kHz, the frequencies most attenuated by the earplug. After removal of the earplug, ARTs started to return to baseline relatively quickly, and were not significantly different from baseline by 4–24 h. There was a trend for the recovery to occur quicker than the onset. The changes in ARTs are consistent with a frequency-specific gain control mechanism operating around the level of the ventral cochlear nucleus in the treatment ear, on a time scale of hours to days. These findings, specifically the time course of change, could be applicable to other sensory systems, which have also shown evidence of a neural gain control mechanism.

Motion of tympanic membrane in guinea pig otitis media model measured by scanning laser Doppler vibrometry

Otitis media (OM) is an inflammatory or infectious disease of the middle ear. Acute otitis media (AOM) and otitis media with effusion (OME) are the two major types of OM. However, the tympanic membrane (TM) motion differences induced by AOM and OME have not been quantified in animal models in the literature. In this study, the guinea pig AOM and OME models were created by transbullar injection of Streptococcus pneumoniae type 3 and lipopolysaccharide, respectively. To explore the effects of OM on the entire TM vibration, the measurements of full-field TM motions were performed in the AOM, OME and untreated control ears by using scanning laser Doppler vibrometry (SLDV). The results showed that both AOM and OME generally reduced the displacement peak and produced the traveling-wave-like motions at relatively low frequencies. Compared with the normal ear, OME resulted in a significant change of the TM displacement mainly in the inferior portion of the TM, and AOM significantly affected the surface motion across four quadrants. The SLDV measurements provide more insight into sound-induced TM vibration in diseased ears.

Sustained Inner Ear Steroid Delivery via Bioabsorbable Stent: A Tolerability and Feasibility Study on Guinea Pigs.

To determine the feasibility and tolerability of a steroid-eluting middle ear device on an animal model. Prospective experimental. Experimental animal study. Mometasone furoate (MF)-eluting miniature sticks were implanted through a myringotomy incision into the middle ear of 10 guinea pigs. Two additional ears of 2 animals served as controls. Fourteen days after implantation, perilymphatic fluid was collected through an endaural cochleostomy. MF concentrations were measured with high-performance liquid chromatography, and the middle ear mucosal inflammation was graded with hematoxylin and eosin colorations. Fourteen days after implantation, all tympanic membranes had fully healed. An average of 165 ng/mL of MF was detected in the perilymphatic fluid of the experimental ears, and none was measured in control ears. Microscopic residues of the ministicks were found in 90% of the samples, confirming the bioabsorbable properties of this device. Histologic analysis of the middle ear mucosa found similar inflammation profiles in both groups, thereby suggesting middle ear tolerability. MF-coated bioabsorbable miniature stick allows for prolonged delivery over 14 days without injuring the middle ear mucosa. Middle ear-sustained steroid delivery may prove to be beneficial in numerous neurotologic conditions.

Protection of horse ears against Simulid parasitism: Efficacy of a mammal semiochemical solution over 10 hours

Hematophagous insects can be vectors of pathogens and cause significant economic loss in zootechnical production. Among biting insects, many dipteran species feed on horse blood. The black fly (Diptera: Simuliidae) group, is responsible for several disorders in horses and inflicts painful bites that lead to undesirable behaviours in horses, particularly when bites occur in sensitive areas such as the inner ear. A field study was conducted in a French equestrian center during which a semiochemical was applied on horses’ ears to assess repellent efficacy against simulid infestation. During the first phase of the study, efficacy was evaluated over a one hour period. Then, during the second phase of the study, persistency of the effect was tested at 8, 9 and 10h after application. The results of the study’s first phase showed 90% efficacy over one hour, with 121.5 insects found in control ears and 12 insects in treated ears (p=0.001). In the second phase of the study, a total amount of 411 insects were observed on control ears whereas only 2 insects were observed on treated ears (p<0.0001); the treatment remained over 98% effective up to 10hours after application. When using a slow release excipient, this semiochemical may offer at least 10h of protection against simulids. This safe, efficient, and long lasting protection could help horses and their owners to manage simulid parasitism.

Endolymphatic space size in patients with Meniere’s disease and healthy controls

Conclusions: The incident ratios of cochlear and/or vestibular endolymphatic hydrops (EH) were significantly higher in the affected ears of patients with Meniere’s disease (MD) than in the ears of healthy controls. There were no significant differences between controls and the contralateral ears of MDs. Objectives: The aim was to compare the incidence ratios of EH between unilateral/bilateral MD and controls using 3T magnetic resonance imaging (MRI) with intravenous gadolinium. Methods: A total of 41 patients were diagnosed with MD: 32 with unilateral MD (uMD) and nine with bilateral MD (bMD). Fifteen healthy volunteers were enrolled as controls. The patients underwent 3T MRI 4 h after intravenous injection of gadolinium. Results: Cochlear EH was present in 3.3% of 30 ears of 15 controls, 6.3% of 32 contralateral (contra) ears of 32 uMDs, 62.5% of 32 affected ears of 32 uMDs, and 55.6% of 18 affected ears of nine bMDs. Vestibular EH was observed in 6.7% of control ears, 3.1% of contra-uMD ears, 65.6% of affected uMD ears, and in 55.6% of affected bMD ears. Either cochlear or vestibular EH was present in 10.0% of control ears, 6.3% of contra-uMD ears, 81.3% of affected uMD ears, and 44.4% of affected bMD ears.

Reduced sensory stimulation alters the molecular make-up of glutamatergic hair cell synapses in the developing cochlea

Neural activity during early development is known to alter innervation pathways in the central and peripheral nervous systems. We sought to examine how reduced sound-induced sensory activity in the cochlea affected the consolidation of glutamatergic synapses between inner hair cells (IHC) and the primary auditory neurons as these synapses play a primary role in transmitting sound information to the brain. A unilateral conductive hearing loss was induced prior to the onset of sound-mediated stimulation of the sensory hair cells, by rupturing the tympanic membrane and dislocating the auditory ossicles in the left ear of P11 mice. Auditory brainstem responses at P15 and P21 showed a 40–50-dB increase in thresholds for frequencies 8–32kHz in the dislocated ear relative to the control ear. Immunohistochemistry and confocal microscopy were subsequently used to examine the effect of this attenuation of sound stimulation on the expression of RIBEYE, which comprises the presynaptic ribbons, Shank-1, a postsynaptic scaffolding protein, and the GluA2/3 and 4 subunits of postsynaptic AMPA receptors. Our results show that dislocation did not alter the number of pre- or postsynaptic protein puncta. However, dislocation did increase the size of RIBEYE, GluA4, GluA2/3 and Shank-1 puncta, with postsynaptic changes preceding presynaptic changes. Our data suggest that a reduction in sound stimulation during auditory development induces plasticity in the molecular make-up of IHC glutamatergic synapses, but does not affect the number of these synapses. Up-regulation of synaptic proteins with sound attenuation may facilitate a compensatory increase in synaptic transmission due to the reduced sensory stimulation of the IHC.

Congestion of mastoid mucosa and influence on middle ear pressure – Effect of retroauricular injection of adrenaline

Micro-CT scanning of temporal bones has revealed numerous retroauricular microchannels, which connect the outer bone surface directly to the underlying mastoid air cells. Their structure and dimensions have suggested a separate vascular supply to the mastoid mucosa, which may play a role in middle ear (ME) pressure regulation. This role may be accomplished by changes in the mucosa congestion resulting in volumetric changes, which ultimately affect the pressure of the enclosed ME gas pocket (Boyle's law). Further, such mucosa congestion may be susceptible to α-adrenergic stimulation similar to the mucosa of the nose. The purpose of our study was to investigate these hypotheses by recording the ME pressure in response to adrenergic stimulation administered by retroauricular injections at the surface of the microchannels.In a group of 20 healthy adults we measured the ME pressure by tympanometry initially in the sitting position, and then in the supine position over a 5 min period with 30 s intervals. In each subject, the study included 1) a control reference experiment with no intervention, 2) a control experiment with subcutaneously retroauricular injection of 1 ml isotonic NaCl solution, and 3) a test experiment with subcutaneously retroauricular injection of 1 ml NaCl-adrenaline solution. In both control experiments the ME pressure displayed an immediate increase in response to changing body position; this pressure increase remained stable for the entire period up to five minutes. In the test experiments the ME pressure also showed an initial pressure increase, but it was followed by a distinct significant pressure decrease with a maximum after 90 s. The test group was injected with both a 5 and 10% adrenaline solution, but the responses appeared similar for the two concentrations.Subcutaneous retroauricular injection of adrenaline caused a significant pressure decrease in ME pressure compared with control ears. This may be explained by the microchannels conveying the adrenaline to the underlying mastoid mucosa, where it may result in a vascular constriction and decongestion, ultimately resulting in a ME pressure decrease. These findings suggest that the microchannels contain vascular connections to the mastoid mucosa, and that the mastoid mucosa is susceptible to vasoactive mediators, which may play a role in ME pressure regulation. Further anatomical and physiological experiments should be carried out to confirm these suggestions including pharmacological interactions with the mastoid mucosa.

Comparison of packing material in an animal model of middle ear trauma

PurposeTo compare the performance of absorbable gelatin sponge (AGS) with polyurethane foam (PUF) as middle ear packing material after mucosal trauma. Materials and methodsUsing a randomized, controlled and blinded study design fifteen guinea pigs underwent middle ear surgery with mucosal trauma performed on both ears. One ear was packed with either PUF or AGS while the contralateral ear remained untreated and used as non-packed paired controls. Auditory brainstem response (ABR) thresholds were measured pre-operatively and repeated at 1, 2, and 6weeks postoperatively. Histological analysis of middle ear mucosa was done in each group to evaluate the inflammatory reaction and wound healing. Another eighteen animals underwent middle ear wounding and packing in one ear while the contralateral ear was left undisturbed as control. Twelve guinea pigs were euthanized at 2weeks postoperatively, and six were euthanized at 3days post-operatively. Mucosal samples were collected for analysis of TGF-β1 levels by enzyme-linked immunosorbent assay. ResultsABR recordings demonstrate that threshold level changes from baseline were minor in PUF packed and control ears. Threshold levels were higher in the AGS packed ears compared with both control and PUF packed ears for low frequency stimuli. Histological analysis showed persistence of packing material at 6weeks postoperatively, inflammation, granulation tissue formation, foreign body reaction and neo-osteogenesis in both AGS and PUF groups. TGF-β1 protein levels did not differ between groups. ConclusionPUF and AGS packing cause inflammation and neo-osteogenesis in the middle ear following wounding of the mucosa and packing.

Detection of eustachian tube openings by tubomanometry in adult otitis media with effusion.

Otitis media with effusion (OME) is a common disease and eustachian tube (ET) dysfunction is widely known to be related to the incidence of OME; however, objective evaluation tools for ET function are lacking. To evaluate ET openings by tubomanometry (TMM) in adult patients with otitis media with effusion (OME), the ET patency of 123 ears, including 63 ears of OME patients and 60 control ears, were tested using TMM and tympanometry. ET patency was evaluated by the R value and ET score, and was compared to the tympanogram results. The eustachian tube dysfunction questionnaire (ETDQ-7) was used to assess the severity of the symptoms in OME patients. The results showed that the rates of restricted opening or blocked ET under pressures of 30, 40, and 50mbar by TMM testing were 10, 5, and 0%, respectively (control group) and 76.19, 66.7, and 57.97%, respectively (OME group) (p<0.05 for all pressure groups). However, the rates were 77.42, 71.97, and 61.29% in the type B tympanogram group, and 75, 62.5, and 46.87% in the type C tympanogram group; no significant difference was found at each testing pressure (p=0.821, 0.246, and 0.516; respectively) between these tympanogram groups. The mean ETDQ-7 score in OME patients was 16.40±10.72, which was significantly negatively correlated with the ET score at 30 and 40mbar (30mbar: correlation coefficient -0.29, p=0.025; 40mbar: correlation coefficient -0.28; p=0.030), but not at 50mbar (correlation coefficient -0.013, p=0.924). These findings showed that ET blockage or delayed opening were found in most adult patients with OME when evaluated by this innovative and semi objective TMM, testing pressures should be considered when assessing the results of TMM in OME patients.

The Influence of Tinnitus on the Audiometric Threshold of Sufferers.

Introduction Tinnitus is a worldwide problem. Objective The objective of this study is to evaluate the audiometric hearing thresholds of adult patients with ongoing tinnitus as their only otological symptom. Methods We evaluated the hearing thresholds of 43 adult patients with ongoing tinnitus and no history of hearing loss from the otolaryngology department of a tertiary health institution at speech and high frequencies. A total of 56 tinnitus ears were compared against 30 contralateral normal ears as well as with the 100 ears of 50 healthy volunteers. Results The study group consisted of 11 (25.6%) males and 32 (74.4%) females with a mean age of 40.9 ± 11.7. The mean Pure Tone Average of the 56 tinnitus ears was 14.8 ± 9, while that of the 100 control ears was 11.2 ± 6 (U = 2078, p = 0.008). The mean pure tone average of the control was also significantly lower than that of the 30 contralateral normal ears of the tinnitus sufferers (U = 1136, p = 0.02). We observed mild to moderate hearing loss in 10 (23%) of the participants. We observed no hearing loss among the control group. Conclusion A proportion of tinnitus sufferers with self-professed normal hearing are likely to have mildly elevated pure tone audiometric thresholds. In patients with unilateral tinnitus, such elevated pure tone hearing thresholds are likely to be in the tinnitus ear and the contralateral non-tinnitus ear.

Mouse model of experimental Eustachian tube occlusion: a surgical technique

Conclusion: The present study demonstrates a mouse model of chronic Eustachian tube (ET) dysfunction using a surgical technique that is reproducible and effective with low mortality and morbidity.Objective: To create a reproducible and effective mouse model of ET obstruction with a low operative morbidity.Methods: Forty healthy, male CBA/CaJ mice underwent the procedure. ET obstruction was performed on one side under general anesthesia; A small piece of dental material (Gutta Percha Points, Meta Biomed, Chungbuk, Korea) was placed via the tympanic orifice of the ET to occlude the entire ET. The contralateral ears of animals served as a control. One month after the operation, all ears were inspected under an operating microscope for signs of ET dysfunction. Primary outcome measures were the signs of ET dysfunction inspected through tympanic membrane (TM) 4 weeks after the operation and confirmation of ET occlusion by post-mortem dissection.Results: Forty (100%) of the treated mice ears developed ET dysfunction, as confirmed by the middle ear appearance on otoscopy and dissection post-mortem and 0% of the control ears at 4 weeks. The most common otoscopic signs were thickened TMs and middle ear effusions. No mortality or morbidity occurred either from anesthesia or surgery.