An animal model for external ear canal inflammation.

OBJECTIVE: To develop an animal model for testing efficacy of anti-inflammatory drugs designed to treat external ear canal (EAC) disease. METHODS: Histological and morphometric methods were used to characterize EAC inflammation produced by topical application of tetradecanoylphorbol acetate (TPA) in mice. The effects of both single and repeated TPA applications were studied. A treatment trial was performed to evaluate the effects of a ciprofloxacin/hydrocortisone suspension on TPA-induced EAC inflammation. In 10 animals, two bilateral applications of TPA were made, spaced 24 hours apart. Immediately after the second TPA application, otic suspension was applied unilaterally four times over a 48-hour period. The contralateral EACs were left untreated to provide TPA-only controls. RESULTS: Twenty-four hours after a single TPA application, EAC skin showed polymorphonuclear (PMN) leukocyte infiltration, vascular dilation, and thickening of the dermis and epidermis. Dermal and epidermal thickening were more pronounced after two TPA applications and PMN leukocyte infiltration remained high 48 hours after a second TPA placement. After treatment with the otic suspension, PMN leukocyte counts were reduced by an average of 76% relative to EACs that received TPA only. There was also statistically significant reduction of dermal swelling and a trend toward reduced epidermal thickness. Vascular dilation was clearly reduced as well EACs that received four applications of the suspension alone showed no adverse effects compared with those that received saline. CONCLUSION: TPA-induced inflammation of the mouse EAC provides a suitable model for testing the therapeutic efficacy of anti-inflammatory agents being considered for clinical use.

Open-cavity tympanomastoidectomy.

A large number of considerations determine whether an open-cavity or closed-cavity technique is most appropriate for an individual patient. These considerations in the selection of technique, as well as the advantages and disadvantages of both open-cavity and closed-cavity tympanomastoidectomy are reviewed in this article. Emphasis is placed on the technical details required to produce a problem free and functional open-cavity tympanomastoidectomy.

Salt-load electrocochleography.

OBJECTIVE: To introduce a new protocol for diagnostic electrocochleography using a pretest oral salt load to improve test sensitivity in patients with suspected inner ear fluid imbalance. STUDY DESIGN: A retrospective review of patients who reported vertigo that, by medical history, was suggestive of an inner ear fluid imbalance was preformed. The patients received a complete audiovestibular evaluation that included a baseline electrocochleogram. Despite the incapacitating nature of their vertigo, there were no symptoms or electrophysiologic abnormalities that would isolate an etiologic ear. After the baseline studies, the patients received 4 g of sodium chloride daily for 3 days before repeat electrocochleography. A control group of 13 healthy volunteers with normal baseline electrocochleography and pure tone audiometry was tested under similar conditions. SETTING: This study was conducted at an ambulatory care clinic associated with a tertiary referral medical center. INTERVENTION: Electrocochleography was performed using alternating polarity clicks presented at a rate of 9.7/sec at 95 dB nHL by an extratympanic TIPtrode electrode and recorded with a Nicolet Spirit (Nicolet Instrument Corp., Madison, WI, U.S.A.). Responses were averaged for 1000 sweeps using a 10-msec time base with bandpass filtering from 5 to 1500 Hz. A summating potential/action potential (SP/AP) ratio of 0.37 was considered the upper limit of normal. MAIN OUTCOME MEASURES: Enhancement in the SP/AP ratio from a normal baseline value to > 0.37 after oral salt loading was indicative of a positive test. RESULTS: None of the ears from control subjects had a positive salt load electrocochleogram, and one or both ears in 38% of the patients in the study group with normal baseline SP/AP ratios and symptoms of inner ear fluid imbalance converted to abnormal. The mean SP/AP ratio of the control group for the conditions before and after salt-load was not statistically different (p = 0.48), although the difference in the mean SP/AP ratio in the study group after salt loading was statistically significant (p = 1.329 x 10(-5)). CONCLUSIONS: A group of patients who reported vertigo with no localizing abnormalities had a statistically significant increase in the mean SP/AP ratio after ingestion of a large quantity of sodium chloride. A modest percentage had elevation of the SP/AP ratio above the upper limit of normal for our audiovestibular lab. The localization of a "salt-senstitive" ear could assist the clinician in the management of these difficult problems with long-term medical therapy or surgical treatment when alternative measures fail.

Histologic demonstration of glycosaminoglycans in inner ear fluids.

Hyaluronic acid is a glycosaminoglycan (GAG) which has been demonstrated by biochemical and histochemical methods to be present in inner ear fluids and tissues. However, consistent labeling of hyaluronic acid or other GAGs in inner ear fluid compartments in histologic sections has not been previously reported. Staining and characterization of GAGs in the normal inner ear fluids of humans and guinea pigs are described in this report. It was initially observed that alcian blue produces dense staining of the endolymphatic and perilymphatic fluid compartments in celloidin embedded material. Results obtained with alcian blue were subsequently compared to staining obtained with hematoxylin/eosin and periodic acid/Schiff base. Enzyme digestion was also performed with testicular hyaluronidase (bovine and ovine), streptomyces hyaluronidase, chondroitase ABC, and alpha-amylase. Results of the differential staining and enzyme digestion studies suggest that the substances in inner ear fluids that stain with alcian blue are a combination of chondroitin sulfate-4, -5 and/or -6 and hyaluronic acid.

Postnatal persistence of epidermoid rests in the human middle ear.

It is widely believed that congenital cholesteatoma originates from epidermoid cell rests in the temporal bone. Congenital cholesteatomas of the anterior-superior middle ear may arise from such a rest, known as the epidermoid formation (EF), which has been described by Michaels and others. The EF is thought to disappear by 33 weeks' gestation in most cases; however, if it persists beyond fetal life, it may provide a nidus for cholesteatoma formation. The authors studied human temporal bones from individuals ranging from 20 weeks' gestation to 5 years of age to investigate pre- and postnatal occurrence of the EF. A total of 106 temporal bones were surveyed; 76 of these were fetal specimens and 30 were postnatal. EFs were present in 14 (18.4%) of the fetal specimens; they were identified in four (13.3%) of the postnatal temporal bones, with the oldest being 2 years, 7 months of age. Multiple EFs within a single temporal bone were also present in some cases. Although the EFs were composed of cells morphologically identical to those of the external ear canal epidermis, none of the specimens showed keratinization. These findings support the contention that EFs do occasionally persist into postnatal life and may be a source of cholesteatoma. However, a clear transition from epidermoid formation to unequivocal cholesteatoma has not yet been demonstrated.

Congenital dermoid cyst of the middle ear.

Dermoid cysts of the head and neck are rare lesions comprised of epidermal and mesodermal elements. We report a dermoid cyst presenting in the middle ear of the youngest patient reported to date. Structures of endodermal descent were also identified, but, given that the entire middle ear mucosa is of endodermal origin, specific classification as a teratoma would be imprecise. This lesion is interesting in that it did not directly involve the mastoid. Possible embryologic sites of origin are discussed.

Electrocochleographic evaluation of the guinea pig model of endolymphatic hydrops.

Electrocochleography (ECochG) was used to evaluate cochlear function in guinea pigs with experimentally induced endolymphatic hydrops (ELH) before and after osmotic dehydration with either glycerol or urea. We surgically induced ELH in the right ears of 9 guinea pigs, while the right ears of 6 guinea pigs received a sham operation. The left ears of the 15 animals constituted the normal group. Eight weeks after surgery, summating potential (SP) and action potential (AP) amplitudes were measured prior to and following the administration of glycerol or urea. The SPs and SP/AP ratios were reduced in all groups, with no significant differences among groups or between dehydrating agents. Some of the hydropic ears, however, did show an increased AP threshold and a recruitment effect. In measurements from 6 additional animals, serum osmolarity increased more with urea than with glycerol. The guinea pig model remains valuable for investigation of ELH, even though it differs in significant respects from ELH in humans.

Effect of basic fibroblast growth factor on perforated chinchilla tympanic membranes.

Basic fibroblast growth factor (bFGF) is a polypeptide mitogen which stimulates proliferation of epidermal and connective tissue cells. When applied to tympanic membrane perforations it has been reported to enhance healing and produce connective tissue hyperplasia. Previous work with animal models has shown that hyperplastic alterations of the tympanic membrane play an essential role in cholesteatoma development. This study was designed to further investigate the hyperplastic effects of bFGF and to determine if it might induce cholesteatoma formation during the healing process. Ten chinchillas received bilateral tympanic membrane perforations. In each animal, three doses of bFGF (400 nanograms per dose) were applied to the perforated tympanic membrane on one side; the opposite (control) ear received saline alone. The animals were terminated at either two or four weeks and studied histologically. Although the dosage and administration schedule used were consistent with previous studies utilizing other rodent species, there was little evidence that bFGF affected tympanic membrane healing in chinchillas. In both control and bFGF-treated ears, dense connective tissue occupied the lamina propria of the tympanic membrane, providing an effective barrier against ingrowth of skin toward the middle ear. No cholesteatomas developed in any animals included in the study. The results of this work indicate that the risk of cholesteatoma formation following administration of bFGF is minimal when it is applied short-term to acute perforations.

Summating potential and action potential gradients on and in the vicinity of the round window in guinea pig.

The purpose of this study was to determine the spatial gradients of summating potential (SP) amplitudes, action potential (AP) amplitudes, and SP/AP ratios for recording loci on the round window (RW) membrane and in its vicinity. Sixteen guinea pigs were tested by means of free-field click and tone burst (2.0 kHz) stimuli. Seven recording regions were specified: five equal-area regions on the RW membrane and two basal promontory regions. Statistically significant differences were found between the promontory regions and the RW membrane regions for the SP, AP, and SP/AP obtained with click stimuli, and for the SP and AP obtained with tone burst stimuli. The SP/AP ratio for tone burst stimuli did not differ significantly across the seven regions. The RW membrane was found to be isoelectric, but there were marked spatial gradients on the basal promontory. These results are of consequence for the interpretation of transtympanic electrocochleography recordings.

Use of an implantable hearing device.

PURPOSE: The purpose of this paper was to discuss our experiences with an implantable bone conduction hearing prosthesis, the XOMED Audiant Bone Conductor (Jacksonville, FL). PATIENTS AND METHODS: Twenty-four patients who had been implanted with the Audiant Bone Conductor were interviewed by telephone following implantation. Questions were asked regarding use of the device and subjective benefit. RESULTS: Eleven patients are using their devices, 12 patients are not using their devices, and one patient has been lost to follow-up. Patients using the device report satisfaction and prefer the Audiant to other amplification systems, whereas those not using the device indicate that insufficient amplification or weak magnetic attraction prevent its use. CONCLUSIONS: Analysis of failures has altered our criteria for implantation. With improvements that have been made by XOMED and stricter patient criteria, the Audiant should be considered a viable amplification alternative for certain hearing-impaired patients.

Middle ear mucocele: an unusual complication of the tranlabyrinthine approach to acoustic neuroma.

The complications of posterior fossa surgery continue to decrease in incidence as our collective experience broadens. Most complications are seen in the immediate postoperative period and the minimized by careful attentiveness to subtle changes in mental status, vital signs, and cranial nerve examination. Long-term follow-up is necessary to identify tumor recurrence, but strict imaging protocols as yet do not exist to facilitate the early identification of recurrent disease, as recurrence is very rare. We report the first case of secondary mucocele formation in the middle ear cleft following translabyrinthine excision of an intracanalicular acoustic neuroma. This complication was found in the fourth postoperative year on routine magnetic resonance imaging, which itself followed previously normal contrasted magnetic resonance imaging in the second postoperative year. The genesis of this complication and possible treatment options are discussed.

Use of a screening RAST in a large neuro-otologic practice.

Evidence in the literature emphasizes the role of the immune system in disorders of the inner ear and eustachian tube. We initially investigated the presence of inhalant allergy in selected patients seen for otologic problems by means of a screening radioallergosorbent test (RAST), using either a microscreen or a limited antigen panel. This study analyzed the results of tests performed over a 2-year period on 186 patients seen by one of us (WLM) for treatment of vertigo (66%), tinnitus (63%), hearing loss (49%), aural fullness (48%), Meniere's quadrad (27%), balance disturbance other than true vertigo (21%), and eustachian tube dysfunction (4%). We found an incidence of immunoglobulin E-mediated hypersensitivity of nearly 40% in a patient population selected solely for neuro-otologic symptoms and not for sinonasal symptoms. This figure is more than double that quoted for the general population. We also found a surprisingly high incidence of mold antigen atopy in this selected population. Allergy can contribute to a number of otologic symptoms, including eustachian tube dysfunction, vertigo, tinnitus, hearing loss, aural fullness, and nonspecific balance disturbance. Allergy also has been emphasized as an etiologic factor in a portion of patients diagnosed with Meniere's syndrome. A screening RAST, combined with clinical evaluation, appears to be an excellent tool for evaluating these patients for inhalant allergy as part of a comprehensive workup.

External and middle ear pathology in TGF-alpha-deficient animals.

Transforming growth factor-alpha (TGF-alpha) is a growth-regulatory peptide found in a wide range of embryonic and adult tissues. TGF-alpha is produced by keratinocytes and has been reported to be overexpressed in several epidermal diseases, including middle ear cholesteatoma. This report describes ear pathology in the waved-1 mutant mouse, which is severely deficient in TGF-alpha. Morphologic changes of the external and middle ear were studied histologically in waved-1 mutants 2 weeks to 6.5 months of age. Abnormalities found in the mutants included epidermal hyperplasia of the external ear canal (EAC) and tympanic membrane (TM) and enlargement of specialized sebaceous glands adjacent to the cartilaginous EAC. Sebum and desquamated keratin progressively accumulated within the EAC, displacing the TM into the middle ear. These changes appear similar to those occurring in Mongolian gerbils, which are known to develop cholesteatoma. The alterations found in waved-1 mutants are discussed in relation to the possible involvement of TGF-alpha in cholesteatoma pathogenesis.

Effect of topical hyaluronic acid on experimental cholesteatoma.

PURPOSE: Inflammation and connective tissue hyperplasia are believed to be important etiological factors in cholesteatoma pathogenesis. Previous work has shown that topically applied hyaluronic acid can reduce connective tissue proliferation in healing wounds and accelerate healing of tympanic membrane perforations. This study was undertaken to determine whether the antiproliferative effect of hyaluronic acid may inhibit propylene glycol-induced cholesteatoma in an animal model. MATERIALS AND METHODS: A 60% propylene glycol solution was injected bilaterally into the middle ear cavities of 20 adult chinchillas. The control group (N = 10) received propylene glycol alone. In addition to propylene glycol injections, the experimental group (N = 10) received repeated bilateral topical applications of 1.5% hyaluronic acid onto the tympanic membranes. Animals were killed at 4 weeks for gross and light microscopic examination. RESULTS: Seven control and 10 experimental animals survived the full 1-month study period. At the end of that time, cholesteatoma was found in 71% (10/14) of control ears and 70% (14/20) of experimental ears. Tympanic membrane structure did not differ significantly between groups by light microscopy and, in all animals, cholesteatomas originated by migration of hyperplastic epidermis through the tympanic membrane, as has been observed in previous studies using this animal model. CONCLUSION: Under the conditions of this study, topical hyaluronic acid had no significant effect on cholesteatoma formation.

Simultaneous comparison between transtympanic and extratympanic electrocochleography.

Electrocochleography (ECoG) has become a mainstay in the diagnostic armamentarium used by otolaryngologists and audiologists in the evaluation of patients suffering auditory and vestibular symptoms. Controversy exists, however, regarding the relative accuracy of ECoG when recorded with a non-invasive external auditory canal (EAC) electrode as compared to that recorded using a transtympanic electrode. In an effort to resolve this controversy, 19 healthy volunteers (37 ears) with no history of otologic disease or symptoms and a normal screening pure-tone audiogram were studied. For each volunteer, a transtympanic electrode was placed on the cochlear promontory bilaterally under iontophoretic anesthesia followed by the immediate placement of an EAC TIPtrode (Etymotic Research Laboratory, Elk Grove Village, Illinois). Signals from both the transtympanic electrode and the TIPtrode were recorded simultaneously following click stimulus using the Nicolet CA 1,000. Preliminary analysis of these recordings identify no significant difference in summating potential/action potential ratios between EAC and transtympanic electrodes in this normal subject population.