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PubMed1997

Development of tympanosclerosis: can predicting factors be identified?

HYPOTHESIS: The etiological hypothesis is that there might be factors triggering an immunological chain reaction that eventually leads to tympanosclerosis formation. BACKGROUND: Tympanosclerosis is a condition leading to a calcification process in the middle ear and, occasionally, also to the lining of the inner ear. This sometimes leads to hearing loss due to fixation of the middle ear ossicles. In severe cases. deafness may occur as a result of the inner ear impairment. Surgery is the treatment offered, often with poor long-term results, and, alternatively, prescription of hearing aids. Some patients develop tympanosclerosis after mild inflammatory otitis media processes whereas some heal without tympanosclerosis after more aggressive infections. This difference may be due to individual variations in the inflammatory response. The biological mechanism of calcification in tympanosclerosis is probably similar to that occurring in other calcifying tissues due to diseases. METHODS: The present investigation was performed to develop methods for immunohistochemical analyses of this delicate tissue consisting of both hard bone and the very thin tympanic membrane. Sprague-Dawley rats were inoculated with a suspension of Streptococcus pneumoniae, type 3, into the middle ear and sacrificed after 1 week up to 6 months. A new technique was elaborated where the whole specimen was prefixed briefly and then en bloc incubated with the primary antibodies and after that decalcified in edetic acid (EDTA). Primary antibodies against macrophages were used for the immunohistochemical staining. RESULTS: Acute otitis media was successfully induced in the rats and myringosclerosis was seen in 30% of the animals, often localized close to the bony frame where macrophages could also be detected. CONCLUSIONS: Acute otitis media and myringosclerosis were introduced in the animals. Conventional immunological techniques were tested on this delicate tissue. A new method for immunohistochemical staining was elaborated in which specimens were stained en bloc before decalcification and sectioning were performed. Expression of macrophages was demonstrated in the tympanic membrane.

Animals↗
PubMed1980

Cochlear mechanics: implications of electrophysiological and acoustical observations.

Implications of the spatial distribution of distortion products (2f1--f2) and (f2--f1) observed from populations of cochlear nerve fibers for cochlear mechanics are reviewed (the terms f1 and f2 represent the primary stimulus frequencies; f1 < f2). Characteristics of the distortion products (2f1--f2) and (f2--f1) in the ear-canal sound pressure of the cat and the chinchilla are investigated. Physiological origin of the acoustic distortion product (2f1--f2) is supported by demonstrations of the vulnerability of the distortion product to anoxia, to overstimulation and to cyanide perfusion of the cochlea. Observations are presented describing the dependence of levels of acoustic distortion products (2f1--f2) and (f2--f1): (1) on primary levels; (2) on f2 with iso-f1; and (3) on f1 and f2 with iso-(2f1--f2). Observations and interpretations are discussed in support of the conclusions: (1) that the distortion product (2f1--f2) in the ear-canal sound pressure observed in our studies is not generated in the experimental apparatus, in the eardrum, or in the middle ear but in the primary-frequency region of the cochlea; (2) that the distortion-product generation requires normal physiological processes in the cochlear sensory apparatus but not the neural activity; and (3) that the distortion-product is mechanically propagated from the generation region in the cochlea toward the distortion-frequency place and toward the stapes, through the middle ear, and into the ear canal involving gross motions of the cochlear partition and the middle-ear ossicles. It is now inevitable that we accept the notion that, in a normal ear, manifestations of significant nonlinear behavior are present in the mechanical response of the middle ear and the cochlea at most of the physiologically normal sound pressure levels.

Acoustic Stimulation↗
PubMed1998

Eya1 expression in the developing ear and kidney: towards the understanding of the pathogenesis of Branchio-Oto-Renal (BOR) syndrome.

Branchio-Oto-Renal (BOR) syndrome is an autosomal dominant, early developmental defect characterised by varying combinations of branchial (fistulas, sinuses, and cysts), outer, middle and inner ear, and renal anomalies. The gene underlying this syndrome, EYA1, is homologous to the Drosophila developmental gene eyes absent which encodes a transcriptional co-activator required for eye specification. We report here the temporal and spatial pattern of expression of the murine homologue, Eya1, throughout ear and kidney development in relation to the anomalies of BOR syndrome. The expression of Eya1 in the branchial arch apparatus (namely in the 2nd, 3rd, and 4th branchial clefts and pharyngeal pouches) at embryonic day (E)10.5, can be correlated with the branchial fistulas, sinuses, and cysts but not with the outer and middle ear anomalies. In contrast, Eya1 is expressed during the slightly more advanced stage of outer and middle ear morphogenesis at E13.5, in the mesenchyme adjacent to the first branchial cleft (the cleft will give rise to the external auditory canal and the surrounding mesenchyme to the auricular hillocks) and surrounding the primordia of the middle ear ossicles, and in the epithelium of the tubotympanic recess (the future tympanic cavity). During early inner ear development, Eya1 is expressed in the ventromedial wall of the otic vesicle (the site of the future sensory epithelia), in the statoacoustic ganglion, and in the periotic mesenchyme, consistent with the cochlear anomalies and sensorineural hearing loss of BOR syndrome. Subsequently, Eya1 expression is observed in the differentiating hair and supporting cells of the sensory epithelia, as well as in the associated ganglia, and persists after differentiation has taken place. This suggests that, in addition to a role in the morphogenetic process, Eya1 could also be implicated in the differentiation and/or survival of these inner ear cell populations. Finally, Eya1 expression in the condensing mesenchymal cells of the kidney is consistent with the excretory and collecting system anomalies of BOR syndrome. From the comparison of the Eya1 and Pax2 expression patterns during ear and kidney development, a contribution of these two genes to the same regulatory pathway can only be suggested in the mesenchymal-epithelial transition directing renal tubule formation.

Animals↗
PubMed1990

Retinoid-induced ear malformations.

Treatment of pregnant Sprague-Dawley rats with retinoic acid or etretinate pregnancy day 8.5 to 9.0 resulted in craniofacial defects in 100% of the embryos. A morphologic investigation of the malformations occurring in the ear was performed. Outer ears were missing, microtic, low-placed, and dorsally situated. External acoustic meatus was short or absent. Middle ear structures were delayed in differentiation, middle ear ossicle primordia were hypoplastic and malformed, the stapedial artery and facial nerve were hypoplastic, and their relation to the stapes was variable. In the inner ear, the otic capsule was thick, the cochlea had fewer turns and the semicircular ducts showed poor differentiation.

Abnormalities, Drug-Induced↗
PubMed1984

Congenital anomalies of the ear resulting from cyclophosphamide treatment in the rat.

A single dose of cyclophosphamide (20 mg/kg) administered on day 12 of gestation to CF rats resulted in microtia in 97.5% of fetuses at term. The ears of affected fetuses were low set and dorsally placed. Histological examination revealed persistence of meatal plug, branching of the primordium of external acoustic meatus, periotic hemorrhages, narrowing of tympanic cavity, presence of only one to two primordia of middle ear ossicles, hypoplasia of stapedial artery, a maximum of two turns of cochlea and under differentiation of the organ of Corti and the semicircular ducts. Hemorrhages in and around the region of the ear were extensive. Bilaterally symmetrical distribution of microtia and consistency of associated anomalies suggest that this is a good animal model for further investigation into the pathogenetic mechanisms of these ear anomalies.

Animals↗
PubMed1997

The Er:YAG laser in ear surgery: first clinical results.

BACKGROUND AND OBJECTIVE: The goal of this study was to gain experiences about the possibilities and limits of the Er:YAG laser for ear operations. STUDY DESIGN/PATIENTS AND METHODS: Eighty-three ear operations were performed with the aid of an Er:YAG laser: 32 stapedotomies, 15 tympanoplasties type III, 10 tympanoplasties type I, 18 ear operations in cholesteatoma, and 8 removals of hyperostosis in the outer ear canal. RESULTS: The Er:YAG laser facilitated stapedotomies and removal of hyperostosis from the outer ear canal. In cases of beginning cholesteatoma, the Er:YAG laser allowed matrix removal of the ear ossicles left in situ. Furthermore, in tympanoplasty it was possible to achieve an osteosynthesis of the auditory ossicles, which was done for the first time during this study. No hearing loss attributable to laser dose was found during postoperative hearing tests. CONCLUSION: The Er:YAG laser seems to become a useful tool in middle ear surgery.

Adolescent↗
PubMed1995

Ear malformations in the mouse embryo following maternal administration of triazene, with clinical implications.

Triazene administration to 10-day pregnant mice gave rise to severe ear abnormalities, including middle ear ossicle malformations. The head of the malleus and the body of the incus were sometimes absent. In some instances, the stapes appeared dysplastic. The stapedial artery was often quite dilated, as well as other cephalic vessels, but qualitatively normal. Severe inner ear abnormalities were observed, as well as auditory nerve disruption, which was associated with central nervous system lesions. Multiple haematomas were present in the embryonic face, but ear abnormalities occurred even in the absence of local hemorrhages. We postulate a direct effect of the teratogen on the branchial mesenchyme. This model seems to be useful for the comprehension of human middle ear abnormalities, but does not constitute a phenocopy of hemicranial microscomia.

Abnormalities, Drug-Induced↗
PubMed2000

["Vibrant Soundbridge" middle ear implant for auditory rehabilitation in sensory hearing loss. I. Clinical aspects, indications and initial results].

BACKGROUND: The adequate therapy for patients suffering from a sensory hearing loss consists of fitting electronic hearing devices. Conventional hearing aids, however, present with significant inherent drawbacks such as insufficient amplification in the high frequency range, problems with the ear mold (feed back, occlusion, external otitis), or distortion of sound with an "unnatural" hearing impression. METHODS: The partially implantable middle ear device Vibrant Soundbridge provides a sound wave conversion into mechanical vibrations at the middle ear ossicles using the Floating Mass Transducer (FMT). The audiological advantages are due to a direct moving force to the perilymph via incus and stapes. The Vibrant Soundbridge system is indicated in patients with a medium to severe symmetrical sensory hearing loss and a normal middle ear. Candidates need previous experience with conventional hearing aids without satisfactory results. RESULTS: The eight operated patients report a "natural" quality of sound and speech, a better hearing perception at high frequencies and the absence of feed back phenomena. Audiological evaluation and questionnair results support the patients subjective hearing impression. CONCLUSIONS: The Vibrant Soundbridge improves hearing quality in patients with sensory hearing loss. The hearing implant is indicated in particular in patients that are unable to wear conventional hearing aids.

Adult↗
PubMed2001

An ossified Meckel's cartilage in two Cretaceous mammals and origin of the mammalian middle ear.

An ossified Meckel's cartilage has been recovered from two early Cretaceous mammals from China. This element is similar to Meckel's cartilage in prenatal and some postnatal extant mammals and indicates the relationship of Meckel's cartilage with the middle ear in early mammals. The evidence shows that brain expansion may not be the initial factor that caused the separation of postdentary bones from the dentary as middle ear ossicles during mammalian evolution. The failure of the dentary to seize reduced postdentary elements during ontogeny of early mammals is postulated as an alternative mechanism for the separation. Modifications of both feeding and hearing apparatuses in early mammals may have led to the development of the definitive mammalian middle ear.

Animals↗
PubMed1985

Recent advances in otitis media with effusion.

OME is similar to other chronic inflammatory diseases with the additional fact that ventilation of the middle ear is an extremely important and necessary part of therapy. Antimicrobial therapy alone may not cure middle ear inflammatory disease as long as Eustachian tube dysfunction persists. If Eustachian tube dysfunction and middle ear fluid persists, all forms of immunologic reactivity may occur in the middle ear which may result in persistent effusion and damage to the mucosal system, to the middle ear ossicles, and to the mastoid mucosal system. These changes may require more aggressive surgical management. It is obvious that we must learn more about the physiology and pathophysiology of the Eustachian tube; about understanding of the systemic, and particularly the local humoral and cell-mediated immune response in the middle ear. Finally, we must determine the potential role of inflammatory mediators, both in the protection against disease and also in the potential role that they play in tissue injury. Encouraging progress is being made in all of these areas and it seems likely that the increased research interest and productivity from laboratories throughout the world will eventually lead to the goal of enhanced prevention and improved treatment of OME.

Child, Preschool↗
PubMed2004

Three-dimensional finite element modeling of human ear for sound transmission.

An accurate, comprehensive finite element model of the human ear can provide better understanding of sound transmission, and can be used for assessing the influence of diseases on hearing and the treatment of hearing loss. In this study, we proposed a three-dimensional finite element model of the human ear that included the external ear canal, tympanic membrane (eardrum), ossicular bones, middle ear suspensory ligaments/muscles, and middle ear cavity. This model was constructed based on a complete set of histological section images of a left ear temporal bone. The finite element (FE) model of the human ear was validated by comparing model-predicted ossicular movements at the stapes footplate and tympanic membrane with published experimental measurements on human temporal bones. The FE model was employed to predict the effects of eardrum thickness and stiffness, incudostapedial joint material, and cochlear load on acoustic-mechanical transmission through the human ossicular chain. The acoustic-structural coupled FE analysis between the ear canal air column and middle ear ossicles was also conducted and the results revealed that the peak responses of both tympanic membrane and stapes footplate occurred between 3000 and 4000 Hz.

Acoustic Stimulation↗
PubMed1989

A temporal bone preparation for the study of cochlear micromechanics at the cellular level.

An in vitro preparation of the guinea pig temporal bone was developed for studying the micromechanical behaviour of the cochlea. The preparation consists of the cochlea opened at the apex, allowing observation of cellular structures within the cochlear partition with an optical sectioning microscope and measurements of cellular vibration with laser interferometry. The middle ear ossicles and the tympanic membrane are left intact as well as the bony part of the external auditory canal, which is used for delivering a sound stimulus to the cochlea.

Acoustic Stimulation↗
PubMed2004

Axial mesodermal dysplasia sequence: autopsy findings.

We describe an infant with the phenotype of the "axial mesodermal dysplasia spectrum" who had the oculo-auriculo-vertebral sequence and caudal dysgenesis. Postmortem studies identified anomalies of the middle ear ossicles, and muscles, in association with microtia and atresia of the external auditory canals, but no cerebral abnormalities.

Abnormalities, Multiple↗
PubMed2001

High-resolution imaging of the middle ear with optical coherence tomography: a feasibility study.

BACKGROUND: Optical coherence tomography (OCT) is a new medical imaging technology that generates cross-sectional images of tissue microstructure with micron-scale resolution. Optical coherence tomography is analogous to ultrasound, measuring the intensity of infrared light rather than acoustical waves. OBJECTIVE: To demonstrate the feasibility of using OCT for ultra-high-resolution imaging of the middle ear via ex vivo imaging studies of human tissue. DESIGN: Images of the tympanic membrane and middle ear were acquired ex vivo, through the ear canal, without perforating the tympanic membrane. MATERIALS: Four excised intact temporal bones and the auditory apparatus were harvested from cadavers and imaged fresh, without previous fixation. RESULTS: The resulting images were compared with the gross sample and verified the ability of OCT to delineate relevant structures, such as the tympanic membrane and its sublayers, and the middle ear ossicles, nerves, and tendons at higher resolutions than possible with standard clinical imaging technologies. CONCLUSION: The ability of OCT to produce high-resolution images of tissue structure, without contact and in real time, as well as its ability to be integrated with endoscopes, suggests that this technology could become a useful modality for the diagnosis and management of a range of clinical middle ear abnormalities.

Ear, Middle↗
PubMed1991

Shape and derived geometrical parameters of the adult, human tympanic membrane measured with a phase-shift moiré interferometer.

The shape of the tympanic membrane is fairly complex and seems to be of significant importance in the coupling of the acoustic sound pressure in the external ear canal to the motion of the middle ear ossicles. A moiré shift interferometer was used to measure with great precision the shape of the external surface of human tympanic membrane. The dense matrix of z(x,y) values thus obtained is used to calculate different geometrical parameters (area, curvature, ...). We show further how the same data can be used to specify exactly the shape of the tympanic membrane in a mathematical finite-element model of the middle ear.

Adult↗
PubMed1994

Case reports: heterotopic brain tissue of middle ear associated with cholesteatoma.

Heterotopic brain tissue reportedly occurs occasionally in various sites, including rare occurrences in the middle ear. Association with cholesteatoma in middle ear cases, however, has not been reported yet. In this article, the authors describe three cases of heterotopic brain tissue in the middle ear associated with cholesteatoma: a 3-year-old boy with recurrent meningitis resulting in right acute otitis media and bony dehiscence of the right attic; a 36-year-old man with chronic right ear infections, right radical mastoidectomy 2 years previously, and brain herniation through the tegmen tympani; and a 65-year-old man with chronic otitis for many years, right ear surgery 25 years previously, and extensive involvement of right middle ear ossicles and mastoid antrum by cholesteatoma. The heterotopic brain tissue in each of these cases was diagnosed by histologic examination, and its glial component was confirmed by immunohistochemical staining for glial fibrillary acidic protein. After a microscopic review of 40 additional surgical pathology cases of cholesteatoma, no evidence of heterotopic brain tissue was found. With these findings, it is suggested that the unusual occurrence of heterotopic brain tissue in the middle ear associated with cholesteatoma may result from local destruction of bone secondary to the cholesteatoma, otitis media, meningitis, or previous surgery.

Adult↗
PubMed1999

Middle ear defects associated with the double knock out mutation of murine goosecoid and Msx1 genes.

A number of developmental regulatory genes, including homeobox genes, are dynamically expressed in the mammalian cephalic ectomesenchyme during craniofacial morphogenesis. Owing to the vast amount of gene knock out experiments, functions of such genes are now being revealed in the mammalian skeletal patterning process. The murine goosecoid (Gsc) and Msx1 genes are expressed during craniofacial development and each mutant mouse displays intriguing facial abnormalities including those of middle ear ossicles, suggesting that both genes play roles in spatial programming of craniofacial regions. In order to examine whether these genes could function in concert to direct particular craniofacial morphogenesis, double knock out mice were analyzed. The phenotype of the double mutant mice was restricted to the first arch derivatives and was apparently additive of the single gene mutant mice, implying region specific genetic interactions of these homeobox genes expressed in overlapping regions of middle ear forming ectomesenchyme. Our results also suggested that the patterning of distal portions of the malleus depends on the tympanic membrane, for which normal expressions of both the genes are prerequisite.

Animals↗
PubMed2007

Microtia, severe micrognathia and absent ossicles: auriculo-condylar syndrome or new entity?

The differential diagnosis of syndromes with anomalies of the first and second branchial arches includes the oculo-auriculo-vertebral syndrome, the Treacher-Collins syndrome, the acrofacial dysostoses (including Nager and Miller syndromes), the dysgnathia complex and the auriculo-condylar syndrome. Isolated microtia may also be present with involvement of other facial structures and distant organs. We report here a patient with first and second branchial arch anomalies, born to consanguineous parents. Pertinent physical findings include severe micrognathia, absence of the upper portion of the helices, atresia of the external meati and absence of the middle ear ossicles, mildly down-slanting palpebral fissures and a highly arched palate with a submucous cleft. Discussion of the differential diagnosis highlights the clinical overlap between these conditions. This constellation of findings may represent a more severe manifestation of the auriculo-condylar syndrome or a previously undescribed syndrome.

Adolescent↗