Genetic aspects of familial Ménière's disease.

OBJECTIVE: Ménière's disease (MD) is a chronic illness characterized by sensorineural hearing loss, recurring vertigo attacks, and tinnitus. It is possibly of multifactorial origin, although several families with autosomal dominant inheritance and reduced penetrance have been described. To elucidate the genetic basis of MD, patients and their families were investigated, and linkage analysis was performed. STUDY DESIGN: Retrospective and prospective family survey. PATIENTS AND METHODS: Of 193 patients diagnosed with MD, 37 patients could be ascertained as having a positive family history, which means a frequency of 19.2%. Nineteen families with 81 members (52 positive for MD and 29 negative for MD) were investigated according to the guidelines of the Committee on Hearing and Equilibrium of the American Academy of Otolaryngology. Blood samples were obtained, and a genome-wide linkage analysis was performed with microsatellite markers. RESULTS: Age of onset diminished in subsequent generations. We found suggestive evidence of linkage assuming heterogeneity of MD on chromosome 5 with a maximum multipoint logarithm of the odds of linkage (LOD) score of 1.9 for 13 of 17 families and a potential region on chromosome 12 for 8 families. Of the 81 subjects, 27 (33.3%) reported MD only, 25 (30.9%) reported migraine and MD, and 7 (8.6%) reported migraine only. CONCLUSION: Family trees suggest an autosomal dominant inheritance with reduced penetrance and anticipation. A probable candidate region for MD was located on chromosome 5.

[How to create a self-cleaning open mastoid cavity]. / Die Anlage einer selbstreinigenden offenen Mastoidhöhle.

Our experience from multiple open mastoid cavity revisions is that some of the well-proven techniques to create a self-cleaning small open cavity are not anymore practiced everywhere.The crucial steps are to considerably drill down the facial ridge, as well as the lateral bone (to the level of the sigmoid sinus) and - in cases of a well pneumatized mastoid - to ground down the mastoid tip. The bony rims should be smoothened with a diamond burr. Furthermore, the size of the cavity can be reduced by partial obliteration of the retrofacial space and the sinus-dura-angle using bone substitutes. In our hands cartilage chips have proven to be a good substitute, hydroxy apatite pellets or a musculoperiosteal flap according to Palva might be used alternatively. Finally a wide auditory canal entrance has to be created. By applying these techniques, for a selected number of cases the "open technique" still represents an essential part of cholesteatoma surgery these days.

Hyperfractionated accelerated radiotherapy versus conventional fractionation both combined with chemotherapy in patients with locally advanced head and neck carcinomas: a retrospective analysis of a monoinstitutional series.

OBJECTIVE: Hyperfractionated accelerated radiotherapy (HART) has been combined with chemotherapy (CC) for locally advanced head and neck cancer, but no data from randomized trials are available for a comparison with conventionally fractionated radiotherapy (CFRT) and CC. METHODS: This monoinstitutional retrospective study compares the results of both treatment schedules: 315 patients with locally advanced carcinoma (UICC stage III and IV) of the oral cavity and the orohypopharynx were treated from January 1990 to March 2006 with a radiochemotherapy combination based on mitomycin C and fluorouracil (HART-CC: 203 patients, CFRT-CC: 112 patients, total dose: 70-72 Gy) with curative intent. RESULTS: Two- and 4-year survival was 60 and 42 (HART-CC) and 59 and 42% (CFRT-CC; p = 0.82, log-rank test), respectively. Using multivariate Cox regression, pretreatment hemoglobin level, N stage, tumor site but not the year of treatment, gender and T stage were significant prognosticators for survival. For locoregional control, only N stage was significant. The prognostic value of these pretreatment factors did not variate with the fractionation schedule used. CONCLUSIONS: In combination with CC, there was no trend towards an improved efficacy of HART in comparison with CFRT.

The GNAS1 T393C polymorphism predicts survival in patients with advanced squamous cell carcinoma of the larynx.

OBJECTIVES/HYPOTHESIS: In previous studies, we have demonstrated that the T-allele of a specific single nucleotide polymorphism (SNP) in the Galphas gene (T393C) correlates with increased Galphas expression and hence apoptosis. The T-allele was associated with a favorable outcome in a variety of human cancers, for example, carcinoma of the urinary bladder, kidney, colorectal, oro- and hypopharynx. STUDY DESIGN: The prognostic value of the T393C SNP was retrospectively evaluated in an unselected series of patients treated with curative intent for laryngeal squamous cell carcinomas including all tumor stages with different therapeutic regimens. METHODS: DNA analysis was performed using DNA from paraffin-embedded tissue samples from 157 patients (142 men, 15 women) with a median follow-up of 68 (3-143) months. The various genotypes were correlated with the overall survival. RESULTS: Survival was significantly dependent on the T393C genotype in advanced American Joint Committee on Cancer (AJCC) stages (III-IV) with an apparent gene-dose effect (P = .0437). Five-year survival rates were 76% for TT, 49% for TC, and 43.5% for CC. In multivariate analysis including age at diagnosis, AJCC stage, grade, gender, and T393C genotypes, patients with CC genotype displayed a higher risk for death with a hazard ratio of 2.59 (95% confidence interval: 1.01-6.64, P = .047) compared with the reference group consisting of T393 homozygous individuals. CONCLUSIONS: The T393C SNP is a prognostic marker that could help to identify high risk patients suffering from head and neck cancer.

Association study of the G-protein beta3 subunit C825T polymorphism with disease progression an overall survival in patients with head and neck squamous cell carcinoma.

The T-allele of a common C825T single nucleotide polymorphism (SNP) in the gene GNB3, encoding the G3 subunit of heterotrimeric G-proteins, is associated with a truncated form of the G3 protein that imparts a greater signaling capacity than the alternative C-allele encoding a nontruncated protein. We analyzed the C825T-allele status with regard to disease progression in patients with head and neck squamous cell carcinoma (HNSCC). The prognostic value of the SNP was evaluated in an unselected series of 341 patients treated with curative intent for HNSCC including all tumor stages with different therapeutic regimens. Genotype analysis was done by Pyrosequencing using DNA from paraffin-embedded tissue samples. Genotypes were correlated with relapse-free and overall survival. Proportions of 5-year relapse-free intervals were 62% for CC, 60% for TC, and 42% for TT genotypes. Kaplan-Meier curves revealed a significant genotype-dependent relapse-free interval (P = 0.036). In multivariate analysis with stage, localization, grade, gender, and smoking habits as covariates, GNB3 825T homozygous patients displayed a higher risk for relapse than C825 homozygous patients (TT versus CC, hazard ratio; 95% confidence interval, 1.4-4.8; P = 0.002). The same genotype effect was found for overall survival, TT genotypes were at higher risk for death compared with CC genotypes (hazard ratio, 2.6; 95% confidence interval, 1.6-4.3; P < 0.001), and 5-year survival proportions were 60% for CC, 52% for TC, and 33% for TT. The GNB3 C825T SNP thus represents a host derived prognostic marker in HNSCC, which allows identifying high-risk patients, which could benefit from novel and/or more aggressive therapeutic regimes.

Overall and relapse-free survival in oropharyngeal and hypopharyngeal squamous cell carcinoma are associated with genotypes of T393C polymorphism of the GNAS1 gene.

PURPOSE: In previous studies, we have shown that the T allele of a specific single-nucleotide polymorphism (SNP) in the Galphas gene (T393C) correlates with increased Galphas expression and hence apoptosis. The T allele was associated with a favorable outcome in a variety of human cancers, e.g., carcinoma of the urinary bladder, kidney, and colorectum. EXPERIMENTAL DESIGN: The prognostic value of the T393C SNP was evaluated in an unselected series of patients treated with curative intent for oropharyngeal and hypopharyngeal squamous cell carcinomas, including all tumor stages with different therapeutic regimens. Genotype analysis was done using DNA from paraffin-embedded tissue samples from 202 patients (162 men, 40 women) with a median follow-up of 38 months (1-133 months). The various genotypes were correlated with relapse-free and overall survival. RESULTS: GNAS1 393C homozygous patients displayed a higher risk for disease progression than T393 homozygous patients (hazard ratio CC versus TT, 1.9; 95% confidence interval, 1.1-3.2; P = 0.019). The same genotype effect was observed for overall survival with CC genotypes at higher risk for death compared with TT genotypes (hazard ratio, 1.7; 95% confidence interval, 1.1-2.9; P = 0.015). Multivariate analysis showed that, besides American Joint Committee on Cancer stage, tumor localization, and gender, the T393C polymorphism was an independent prognostic factor for disease progression and death. CONCLUSION: The T393C SNP could be considered as a genetic marker to predict the clinical course of patients suffering from oropharyngeal and hypopharyngeal cancer.

Immunohistochemical evidence of BMP-2, -4 and -7 activity in otospongiosis.

CONCLUSION: This study is the first to show that bone morphogenetic proteins (BMP)-2, -4 and -7 play a role in active phase otosclerotic bone remodelling (otospongiosis). OBJECTIVES: The role of BMPs in various tissue growth and repair mechanisms is an ongoing topic in the literature. BMP-2, -4 and -7 are known to be of major importance in bone formation and repair. Their role in otosclerotic bone transformation has not been analysed previously. The main goal of this study was to perform an immunohistological analysis of BMP-2, -4 and -7 in otoclerosis. MATERIALS AND METHODS: Parts of the stapedial footplates, collected during partial stapedectomies in 30 patients with clinical otosclerosis, were analysed for histological otosclerotic lesions after staining haematoxylin and eosin. Immunohistochemical analysis was performed using polyclonal IgG antibodies for BMP-2, -4 and -7, as well as biotinylated secondary antibodies, avidin-biotin-peroxidase complex reaction and alkaline phosphatase staining. RESULTS: In all, 14 specimens contained otosclerosis; 3 of these were otospongiotic, 8 fibrotic, 2 sclerotic and 1 had both sclerotic and fibrotic lesions. Thus in total 14/30 specimens (47%) showed histological otosclerosis. Only the multiple osteoblasts and osteoclasts in those specimens exhibiting an otospongiotic phase showed distinct immunochemical staining for BMP-2, -4 and -7.

Infections with human rhinovirus induce the formation of distinct functional membrane domains.

The plasma membrane contains distinct domains that are characterized by a high concentration of sphingolipids and cholesterol. These membrane microdomains also referred to as rafts, seem to be intimately involved in transmembranous signaling and often initiate interactions of pathogens and the host cell membranes. Here, we investigated the further reorganization of membrane rafts in cultured epithelial cells and ex vivo isolated nasal cells after infection with rhinoviruses. We demonstrate the formation of ceramide-enriched membrane platforms and large glycosphingolipid-enriched membrane domains and the co-localization of fluorochrome-labeled rhinoviruses with these membrane domains during attachment and uptake of human rhinovirus. Destruction of glycosphingolipid-enriched membrane domains blocked infection of human cells with rhinovirus. Furthermore, our studies indicate that the activation of the acid sphingomyelinase (ASM) is intrigued in the formation of ceramide- or GM1- enriched membrane platforms. Inhibition of the ASM reduces the number of ceramide-enriched platforms and glycosphingolipid-enriched membrane domains. These data reveal a critical role of the ASM for the formation of membrane platforms and infection of human cells with rhinoviruses.

Signaling by way of type IB and II bone morphogenetic protein receptors regulates bone formation in otospongiosis.

HYPOTHESIS: The main goal of this study was to perform an immunohistologic analysis of bone morphogenetic protein receptors (BMPR) in otospongiosis. BACKGROUND: BMP-2, -4, and -7 play an essential role in bone formation and repair. They do so as well in otosclerosis. It has been shown that these BMPs are traceable in osteocytes and osteoclasts in the active phase of otosclerosis (otospongiosis). The role of the different BMP receptors in otosclerotic bone transformation has not been previously analyzed. METHODS: The posterior parts of the stapes footplates, collected during partial stapedectomies in 35 patients with clinical otosclerosis, were analyzed for histologic otosclerotic lesions after hematoxylin staining. Immunohistochemical analysis was performed using polyclonal immunoglobulin G antibodies for BMPR-IA, -IB, and -II, as well as biotinylated secondary antibodies, avidin-biotin-peroxidase complex reaction, and alkaline phosphatase staining with nitroblue-tetrazolium-chloride. RESULTS: Seventeen of 35 (49%) specimens contained otosclerosis, but only 5 of these exhibited an otospongiotic phase. The abundant osteoblasts and osteoclasts in these cases showed distinct immunochemical staining for BMP-2, -4, and -7. In two cases, there could also be found an immense positive staining for BMPR-IB and modest staining for BMPR-II, whereas BMPR-1A always remained negative. CONCLUSION: It was demonstrated for the first time that in otospongiosis, the actions of the BMPs are mediated through BMPR-IB and BMPR-II. To determine this role in detail, further investigations, especially for the phosphorylated Smad proteins within the BMP dependent mediator cascade, will be necessary.

Revision stapes surgery.

We present the results of our revision stapes operations from 1989 to 2004 (n = 217). Long-term follow-up was performed in the first 135 cases. Eighteen of these patients were revised because of inner ear symptoms, predominantly within the first year. One hundred and sixteen cases underwent revision surgery due to conductive hearing loss, on average after 10.6 years. One patient was operated because of dysgeusia. In 1999, we first described inner ear damage after implantation of gold prostheses. Therefore, we developed a titanium implant that was initially investigated in cell culture and subsequently tested in a clinical trial. We report on the most frequent causes that led to revision surgery such as adhesions, prosthetic problems, erosions of the long process of the incus, or refixation of the footplate, and on the different surgical techniques. In a first series of patients with a conductive hearing loss, a significant hearing improvement of 69.4% of these cases was obtained. However, this result very much depends on the selection of cases. There was no case of additional sensorineural hearing loss. Since 1999, we had mainly used titanium implants for replacement in stapes revision surgery. In a second series, a significant hearing improvement of 76.2% was found. One patient with a platinum Teflon implant had to be revised because of vertigo and conductive hearing loss which was observed during MRI.

Prototype of a silicon nitride ceramic-based miniplate osteofixation system for the midface.

OBJECTIVE: The favorable properties of silicon nitride (Si3N4) ceramics, such as high mean strength level and fracture toughness, suggest biomedical use as an implant material. Minor reservations about the biocompatibility of Si3N4 ceramics were cleared up by previous in vitro and in vivo investigations. STUDY DESIGN AND SETTING: A Si3N4 prototype minifixation system was manufactured and implanted for osteosynthesis of artificial frontal bone defects in 3 minipigs. After 3 months, histological sections, computed tomography (CT) scans, and magnetic resonance imaging (MRI) scans were obtained. Finite element modeling (FEM) was used to simulate stresses and strains on Si3N4 miniplates and screws to calculate survival probabilities. RESULTS: Si3N4 miniplates and screws showed satisfying intraoperative workability. There was no implant loss, displacement, or fracture. Bone healing was complete in all animals. The formation of new bone was observed in direct contact to the implants. The implants showed no artifacts on CT and MRI scanning. FEM simulation confirmed the mechanical reliability of the screws, whereas simulated plate geometries regarding pullout forces at maximum load showed limited safety in a bending situation. CONCLUSIONS: Si3N4 ceramics show a good biocompatibility outcome both in vitro and in vivo. In ENT surgery, this ceramic may serve as a biomaterial for osteosynthesis (eg, of the midface including reconstruction the floor of the orbit and the skull base). To our knowledge, this is the first introduction of a ceramic-based miniplate-osteofixation system. Advantages compared with titanium are no risk of implantation to bone with mucosal attachment, no need for explantation, and no interference with radiologic imaging. Disadvantages include the impossibility of individual bending of the miniplates.

Unusual aggressive course of a giant cell tumor of soft tissue during immunosuppressive therapy.

Giant cell tumor of soft tissue with low malignant potential (GCT-ST) is a low-grade, primary soft tissue sarcoma with histological and clinical features similar to giant cell tumor of the bone. The main tumor localizations are the extremities, but it may also occur in the head and neck region. GCT-ST shows a recurrence rate of approximately 15%, but it very rarely metastasizes. The risk of cancer development, especially of the skin, is up to fivefold increased in immunosuppressed patients after organ transplantation. The association of sarcomas and immunosuppressive therapy is best known for Kaposi sarcomas, whereas other types of sarcomas are rarely found. We report of a GCT-ST of low malignant potential, which developed under long-term immunosuppression in a patient 12 years after heart transplantation. The tumor presented with an unusual aggressive course and metastatic site: the parotid gland. Therefore, we suggest that in patients with immunosuppression, even low malignant cancerous lesions should be carefully observed, as their local behavior may be aggressive with development of metastasis.

Laser-tonsillotomy for treatment of obstructive tonsillar hyperplasia in early childhood: a retrospective review.

INTRODUCTION: Tonsillar hyperplasia leading to dyspnea, dysphagia and other symptoms of obstruction represents a common problem especially in young children where tonsillectomy should be avoided in order to preserve the immunological function of the tonsils. Aim of the study was to assess carbon-dioxide-laser-tonsillotomy as a considered alternative procedure to reduce the tonsillar volume in these children. METHODS: Between 1993 and 2004, 109 children with tonsillar hyperplasia without former episodes of tonsillitis received laser-tonsillotomy mostly (n=98) combined with adenoidectomy. The protruding part of the tonsil was reduced by a CO2-laser. Seventy-five children were available for follow-up with a standard questionnaire. Five patients required a subsequent tonsillectomy due to a recurrence of tonsillar hyperplasia. Histological investigations were performed. Twenty-two children were reevaluated by clinical examination. RESULTS: Most of the patients were relieved from obstructive symptoms. There was no occurrence of postoperative hemorrhage or peritonsillar abscesses. The histological investigations on the specimens from later performed tonsillectomy (n=5) showed no evidence of inflammation or scar formations, but open and deep crypts. The clinical examination did not reveal any signs of chronic infections. CONCLUSION: In this retrospective study tonsillotomy with CO2-laser in early childhood leads to a long-term elimination of obstructive symptoms due to tonsillar hyperplasia with minimal discomfort for the patient while preserving normally functioning immunocompetent tonsillar tissue. Further prospective studies are planned.

Antiphospholipid antibodies in patients with sensorineural hearing loss.

Sensorineural hearing loss can be associated with autoimmune diseases and the presence of antiphospholipid antibodies. Sixty patients (mean age 47 years, range 18-76 years) with sudden sensorineural hearing loss were studied with audiograms, stapedial thresholds, otoacoustic emissions, positional and caloric testing. The serologic testing included antibodies against phosphatidylserine and beta(2)-glycoprotein. Additionally, a group of 34 patients (mean age 65 years, range 31-81 years) with normal tension glaucoma was examined because in a previous study these patients were reported to have elevated concentrations of antiphospholipid antibodies with a coincidence of progressive sensorineural hearing loss. The baseline for antiphospholipid antibody levels was established in a control group of 40 healthy blood donors. In 12 of the 60 patients with sudden sensorineural hearing loss, levels of antiphospholipid antibodies were elevated. Antiphosphatidylserine IgM antibodies were significantly lower compared to controls and patients with the combination of hearing loss and normal tension glaucoma (Fisher's exact two-sided test, P < 0.01). Our data suggest that antibodies against beta2-glycoprotein seem to coincidence with an acute event, such as sudden sensorineural hearing loss, whereas antibodies against phosphatidylserine IgG are detectable in the prolonged sequel, such as in patients with progressive sensorineural hearing loss and normal tension glaucoma.

Hyperfractionated accelerated chemoradiation with concurrent fluorouracil-mitomycin is more effective than dose-escalated hyperfractionated accelerated radiation therapy alone in locally advanced head and neck cancer: final results of the radiotherapy cooperative clinical trials group of the German Cancer Society 95-06 Prospective Randomized Trial.

PURPOSE: To report the results and corresponding acute and late reactions of a prospective, randomized, clinical study in locally advanced head and neck cancer comparing concurrent fluorouracil (FU) and mitomycin (MMC) chemotherapy and hyperfractionated accelerated radiation therapy (C-HART; 70.6 Gy) to hyperfractionated accelerated radiation therapy alone (HART; 77.6 Gy). PATIENTS AND METHODS: Three hundred eighty-four stage III (6%) and IV (94%) oropharyngeal (59.4%), hypopharyngeal (32.3%), and oral cavity (8.3%) cancer patients were randomly assigned to receive either 30 Gy (2 Gy every day) followed by 1.4 Gy bid to a total of 70.6 Gy concurrently with FU (600 mg/m(2), 120 hours continuous infusion) days 1 through 5 and MMC (10 mg/m(2)) on days 5 and 36 (C-HART) or 14 Gy (2 Gy every day) followed by 1.4 Gy bid to a total dose of 77.6 Gy (HART). The data were analyzed on an intent-to-treat basis. RESULTS: At 5 years, the locoregional control and overall survival rates were 49.9% and 28.6% for C-HART versus 37.4% and 23.7% for HART, respectively (P = .001 and P = .023, respectively). Progression-free and freedom from metastases rates were 29.3% and 51.9% for C-HART versus 26.6% and 54.7% for HART, respectively (P = .009 and P = .575, respectively). For C-HART, maximum acute reactions of mucositis, moist desquamation, and erythema were lower than with HART, whereas no differences in late reactions and overall rates of secondary neoplasms were observed. CONCLUSION: C-HART (70.6 Gy) is superior to dose-escalated HART (77.6 Gy) with comparable or less acute reactions and equivalent late reactions, indicating an improvement of the therapeutic ratio.

Immunohistochemical investigations on external auditory canal cholesteatomas.

OBJECTIVE: The aim of the study was to analyze the biological behavior of external auditory canal cholesteatoma (EACC). The expression and distribution of relevant markers such as transforming growth factor-alpha (TGF-alpha), epidermal growth factor-receptor (EGFR), and the proliferation marker MIB 1 were studied in comparison with normal auditory meatal skin. BACKGROUND: EACC are uncommon and knowledge concerning etiology and pathogenesis is limited. Whether this is a unique entity remains controversially discussed. MATERIALS AND METHODS: Immunohistochemical methods were used to study the expression and distribution TGF-alpha, EGFR, and the proliferation marker MIB 1 on 15 tissues samples. Only the spontaneous form of EACC was included in this study. RESULTS: Positive immunoreactivity for the proliferation marker MIB 1 could be demonstrated in keratinocytes in the basal and suprabasal layers of the epithelium. The number of MIB 1-positive proliferating cells in cholesteatoma was significantly higher than in normal external auditory skin. Cholesteatoma epithelium also showed an enhanced expression of TGF-alpha and EGFR. Inflammatory infiltrate was observed in the perimatrix to various degrees. CONCLUSION: These results suggest that similar to the middle ear cholesteatoma, a chronic inflammatory process underlies the EACC, and the inflammatory stimuli may alter keratinocyte proliferation.

Type III tympanoplasty applying the palisade cartilage technique: a study of 61 cases.

OBJECTIVE: To determine the morphologic and hearing results of the combined application of the palisade cartilage technique and titanium ossicular replacement prostheses in Type III tympanoplasty. STUDY DESIGN: Retrospective review of 61 tympanoplasties. SETTING: Tertiary referral center. PATIENTS: 59 patients (39 women and 20 men, mean age 36 years, range 7-81 years) consecutively operated on because of cholesteatoma, adhesive otitis, chronic otitis media, subtotal tympanic membrane defects, and tympanofibrosis requiring tympanoplasty with ossiculoplasty. INTERVENTIONS: Tympanoplasty Type III, with application of the palisade cartilage technique and total or partial titanium ossicular replacement prosthesis. MAIN OUTCOME MEASURES: Otoscopic findings and hearing results using a four-frequency pure tone average air-bone gap. RESULTS: A recurrent defect was seen in 1 ear (1.6%). The graft take rate was 100%. There were no extrusions of prostheses. Preoperatively, a pure tone average air-bone gap of 0 to 10 dB was seen in 1 ear, 11 to 30 dB in 30, and 31 to 50 dB in another 30 ears. Postoperatively, the corresponding numbers were 11, 41, and 9 ears, respectively. Hearing results were better in the total ossicular replacement prosthesis group. CONCLUSIONS: The palisade cartilage technique is suitable to manage difficult pathologic conditions in middle ear surgery. It was demonstrated that the palisade cartilage technique can be combined safely with titanium ossicular replacement prostheses. Regarding postoperative hearing results, the negative preselection of pathologic conditions must be considered.

Connexin30 (Gjb6)-deficiency causes severe hearing impairment and lack of endocochlear potential.

The gap junction protein connexin30 (Cx30) is expressed in a variety of tissues that include epithelial and mesenchymal structures of the inner ear. We generated Cx30 (Gjb6) deficient mice by deletion of the Cx30 coding region. Homozygous mutants (Cx30((-/-))) were born at the expected Mendelian frequency, developed normally and were fertile. However, they exhibit a severe constitutive hearing impairment. From the age of hearing onset, these mice lack the electrical potential difference between the endolymphatic and perilymphatic compartments of the cochlea, i.e. the endocochlear potential, which plays a key role in the high sensitivity of the mammalian auditory organ. In addition, after postnatal day 18, the cochlear sensory epithelium starts to degenerate by cell apoptosis. This degeneration process is likely to account for the concomitant decrease of the endolymphatic potassium concentration and the aggravation of the hearing loss in adult Cx30((-/-)) mice. The Cx30 ((-/-)) phenotype thus reveals the critical role of Cx30 both in generating the endocochlear potential and for survival of the auditory hair cells after the onset of hearing. The Cx30 deficient mice may represent a valuable model to study the mechanism of the hearing loss in human patients carrying a homozygous deletion of the CX30 gene (del Castillo et al., 2002, New Engl. J. Med., 346, 243-249).

Reconstruction of the stapes superstructure with a combined glass-ceramic (Bioverit) implant in guinea pigs.

BACKGROUND: Reconstruction of the stapes superstructure continues to be a problem for otologists. Optimal fixation of implants on the stapes footplate has not yet been achieved. METHODS: We postulated that bony fixation, between implant and stapes, could be confined exclusively to the footplate region by modifying the bioactivity of the implant material. Therefore, after removal of the superstructure in guinea pigs a combined biovitro ceramic implant (Bioverit I and Bioverit II) was placed on the stapes footplate in 10 guinea pigs. As a control, we employed a group of 6 animals in which the stapes superstructure was removed without placing any implant. RESULTS: After 25 weeks the implants were found to be dislocated laterally. We observed fixation with the wall of the middle ear. In the control group we also found new bone formation and even a bow shaped regeneration of the stapes superstructure. CONCLUSION: Combined Bioverit stapedial implants were found to routinely fix to the middle ear wall of the guinea pig. The guinea pigs' enormous potential for bone regeneration in the middle ear ossicular chain make this species unsuitable for exploring hypotheses on human middle ear reconstruction.