[Surgery for tympanosclerotic stapes fixation accompanied by malleus fixation at the anterior malleus: report of 2 cases].

Most tympanosclerotic stapes fixation involves fixation or erosion of the malleus and/or incus. This status of the ossicular chain is one reason that ossiculoplasty for tympanosclerotic stapes fixation is more difficult than that for otosclerosis. In some cases, the malleus is fixed only at the anterior, while the incus is intact. In such cases, anterior spinotomy can recover mobilization of the malleus, then a prosthesis can be used for the long process of the incus during ossiculoplasty. We conducted stapedectomy with anterior spinotomy on 3 ears in 2 patients. Over 15 dB of hearing was regained in all 3 ears 6 months after surgery. No significant sensorineural hearing loss was seen in any ear. To adapt this surgical procedure, it is necessary to evaluate preoperative CT findings and the status of the ossicular chain during surgery.

Expression of mucins in mucoid otitis media.

A hallmark of mucoid otitis media (MOM, i.e., chronic otitis media with mucoid effusion) is mucus accumulation in the middle ear cavity, a condition that impairs transduction of sounds in the ear and causes hearing loss. The mucin identities of mucus and the underlying mechanism for the production of mucins in MOM are poorly understood. In this study, we demonstrated that the MUC5B and MUC4 were major mucins in MOM that formed distinct treelike polymers (mucus strands). The MUC5B and MUC4 mRNAs in the middle ear mucosa with MOM were up regulated 5-fold and 6-fold, compared with the controls. This upregulation was accompanied by the extensive proliferation of the MUC5B- and MUC4-producing cells in the middle ear epithelium. Further study indicated that the mucin hyperproduction was significantly linked to CD4+ and CD8+ T cells and/or CD68+ monocyte macrophages. It suggests that MUC5B and MUC4 expression may be regulated by the products of these cells.

Analysis by cDNA microarrays of altered gene expression in middle ears of rats following pneumococcal infection.

OBJECTIVE: Streptococcus pneumoniae is the most common pathogen in otitis media. Infection of the middle ear with S. pneumoniae potentiates development of thick effusion in the middle ear which frequently causes hearing loss and communication disorders in children. What has changed immediately in the middle ear cleft following pneumococcal infection is extensively studied and characterized but what has changed ever after remains elusive. The purpose of this study is to explore the cellular and molecular basis that remains on a longer time after acute pneucmococcal middle ear infection and potentiates development of thick effusion in the middle ear. METHODS: 12 rats were intrabullarly inoculated with pneumococcus at 2.5x10(6) CFU/ear and profiles of gene expression in the middle ear were examined by cDNA microarrays in combination with reverse transcription-polymer chain reaction (RT-PCR) 6 weeks after infection while the morphologic changes in middle ear were simultaneously characterized by histopathologic techniques. Twelve rats receiving phosphate-buffered saline (PBS) served as controls. RESULTS: it demonstrated that pneumococcus infected ears had the expression of the following genes at a high level compared to the controls: mitogenic signaling proteins (mitogen-activated protein kinase [MEK1 and MEK2], helix-loop-helix transcriptional regulators (Id3 and Id1), ion channels (sodium channel beta 1 and sodium channel 2), and mucin glycoproteins (Muc2 and Muc5). The morphology demonstrated a thickened mucosa and submucosa with increased expression of macroglycoconjugates compared to the controls. CONCLUSION: the expression of several genes remains high even after the acute episode of pneumococcal otitis media has been resolved. The up-regulated expression of these genes may serve as the basis for the development of thick effusion and mucous cell metaplasia/hyperplasia once it is complicated with other factors such as dysfunction of the Eustachian tube.

Induction of mucous cell metaplasia by tumor necrosis factor alpha in rat middle ear: the pathological basis for mucin hyperproduction in mucoid otitis media.

Mucoid otitis media (MOM), one of the leading causes of acquired hearing loss in children, is characterized by mucous cell hyperplasia in the middle ear cleft associated with mucin accumulation in the middle ear cavity. The factors that stimulate mucous cell metaplasia-hyperplasia and mucin hyperproduction are poorly understood. Recent studies demonstrated that tumor necrosis factor alpha (TNF-alpha), present in human middle ear effusion, stimulated mucin production in vitro and up-regulated mucin gene expression in vivo. These findings suggest that TNF-alpha is important in the development of mucous cell metaplasia-hyperplasia. This study demonstrated that inoculation of TNF-alpha into the middle ear cavity followed by eustachian tube obstruction stimulated mucous cell metaplasia-hyperplasia in the middle ear cleft, accompanied by abundant mucin or mucin-like glycoproteins in the middle ear effusion--a phenotype of MOM in humans. This finding suggests that TNF-alpha plays a key role in the pathogenesis of MOM through induction of mucous cell metaplasia-hyperplasia and mucin production.

Induction of mucous cell metaplasia in the middle ear of rats using a three-step method: an improved model for otitis media with mucoid effusion.

Otitis media with mucoid effusion, characterized by mucous cell metaplasia in the middle ear cleft and thick fluid accumulation in the middle ear cavity, is a common otological disease that frequently affects young children. Multiple factors are involved in the development of this disease, especially middle ear infection and Eustachian tube dysfunction. In this study, in order to induce otitis media with effusion in rats, we introduced a three-step method, namely inoculation of Streptococcus pneumoniae at 10(7) colony-forming units (CFU)/ear or Haemophilus influenzae at 5 x 10(7) CFU/ear into the middle ear cavity twice at 2-week intervals, followed by Eustachian tube obstruction (ETO) for 4 and 8 weeks. Animals inoculated with phosphate-buffered saline (PBS) twice in the same manner followed by ETO served as controls. Middle ear effusion and mucosa were harvested for evaluation of carbohydrate concentrations and mucous cell density, respectively. We found that rats inoculated with S. pneumoniae twice, followed by ETO at 8 weeks, yielded the highest carbohydrate concentration in middle ear effusion and the highest goblet cell density in the middle ear cavity compared to the H. influenzae and PBS groups. It is tentatively concluded that inoculation of S. pneumoniae at 10(7) CFU/ear into the middle ear cavity of rats twice at 2-week intervals, followed by ETO for 8 weeks, is a promising animal model for otitis media with mucoid effusion which may be valuable for studying the human counterpart.

Feline immunodeficiency virus-mediated gene therapy of middle ear mucosa cells.

HYPOTHESIS: To investigate the feasibility of gene therapy of the middle ear mucosa using a novel vector. BACKGROUND: Given present medications are unable to affect chronic otitis media, cholesteatoma, or tympanic membrane perforation, newer methods of treatment like gene therapy for these diseases must be explored. These genes can then be used to alter cytokines in the middle ear, slow or stop cholesteatoma growth, or improve tympanic membrane perforation healing. Feline immunodeficiency virus (FIV), a new lentiviral vector has been found to have greater than 90% efficiency in transfecting epithelial cells. Therefore, in vivo gene therapy of middle ear mucosa cells was attempted. METHODS: Twenty microliter of 5x10(5) vectors per ml FIV carrying the gene for green fluorescence protein (GFP) was introduced into the middle ears of Sprague-Dawley rats via a bulla approach. RESULTS: Expression of the GFP gene was observed in the middle ear mucosa cells at 1 week post-inoculation indicating transfection. CONCLUSION: Gene therapy of the middle ear is feasible with a FIV-based vector.

[A case of enlarged vestibular aqueduct syndrome with PDS gene mutations].

Enlarged vestibular aqueduct (EVA) is an inner ear anomaly occasionally associated with sensorineural hearing loss (SNHL) and/or dizziness. Recent genetic studies indicate that mutations in the PDS gene may cause EVA. A 10-year-old EVA patient who had undergone annual hearing tests for 7 years had an aunt and cousin who also had hearing loss and EVA, so genetic examinations were conducted for a possible genetic link. Two new PDS gene mutations, S610X and S657N, were found in all 3, including the proband. We discuss the importance of genetic analysis, which offers new insight into SNHL diagnosis and treatment in children.