Mucin Production and Mucous Cell Metaplasia in Otitis Media

Otitis media (OM) with mucoid effusion, characterized by mucous cell metaplasia/hyperplasia in the middle ear cleft and thick fluid accumulation in the middle ear cavity, is a subtype of OM which frequently leads to chronic OM in young children. Multiple factors are involved in the developmental process of OM with mucoid effusion, especially disorders of mucin production resulting from middle ear bacterial infection and Eustachian tube dysfunction. In this review, we will focus on several aspects of this disorder by analyzing the cellular and molecular events such as mucin production and mucous cell differentiation in the middle ear mucosa with OM. In addition, infectious agents, mucin production triggers, and relevant signaling pathways will be discussed

The genetics of cholesteatoma. A systematic review using narrative synthesis

Objective: A cholesteatoma is a mass of keratinising epithelium in the middle ear. It is a rare disorder that is associated with significant morbidity, and its causative risk factors are poorly understood; on a global scale up to a million people are affected by this each year. We have conducted a systematic literature review to identify reports about the heritability of cholesteatoma or any constitutional genetic factors that may be associated with its aetiology. Data Sources: A systematic search of MEDLINE (EBSCO) and 2 databases of curated genetic research (OMIM and Phenopedia) was conducted. Study Selection: The participants and populations of interest for this review were people treated for cholesteatoma and their family members. The studies of interest reported evidence of heritability for the trait, or any association with congenital syndromes and particular genetic variants. Data Extraction: The searches identified 449 unique studies, of which 35 were included in the final narrative synthesis. Data Synthesis: A narrative synthesis was conducted and data were tabulated to record characteristics, including study design; genetic data; and author conclusions. Most of the studies identified in the literature search, and described here, are case reports and so represent the lowest level of evidence. In a few case-reports, congenital and acquired cholesteatoma have been shown to segregate within families in the pattern typical of a monogenic or oligogenic disorder with incomplete penetrance. Evidence from syndromic cases could suggest that genes controlling ear morphology may be risk factors for cholesteatoma formation. Conclusions: This is the first systematic review about the genetics of cholesteatoma; and we have identified a small body of relevant literature that provides evidence of a heritable component for its aetiology. Cholesteatoma is a complex and heterogeneous clinical phenotype, it is often associated with chronic otitis media and with some rare congenital syndromes known to affect ear morphology and related pathologies

Genetic and Epigenetic Alterations of the NF2 Gene in Sporadic Vestibular Schwannomas

BACKGROUND: Mutations in the neurofibromatosis type 2 (NF2) tumor-suppressor gene have been identified in not only NF2-related tumors but also sporadic vestibular schwannomas (VS). This study investigated the genetic and epigenetic alterations in tumors and blood from 30 Korean patients with sporadic VS and correlated these alterations with tumor behavior. METHODOLOGY/PRINCIPAL FINDINGS: NF2 gene mutations were detected using PCR and direct DNA sequencing and three highly polymorphic microsatellite DNA markers were used to assess the loss of heterozygosity (LOH) from chromosome 22. Aberrant hypermethylation of the CpG island of the NF2 gene was also analyzed. The tumor size, the clinical growth index, and the proliferative activity assessed using the Ki-67 labeling index were evaluated. We found 18 mutations in 16 cases of 30 schwannomas (53%). The mutations included eight frameshift mutations, seven nonsense mutations, one in-frame deletion, one splicing donor site, and one missense mutation. Nine patients (30%) showed allelic loss. No patient had aberrant hypermethylation of the NF2 gene and correlation between NF2 genetic alterations and tumor behavior was not observed in this study. CONCLUSIONS/SIGNIFICANCE: The molecular genetic changes in sporadic VS identified here included mutations and allelic loss, but no aberrant hypermethylation of the NF2 gene was detected. In addition, no clear genotype/phenotype correlation was identified. Therefore, it is likely that other factors contribute to tumor formation and growth

The Multifunctional Host Defense Peptide SPLUNC1 Is Critical for Homeostasis of the Mammalian Upper Airway

Otitis media (OM) is a highly prevalent pediatric disease caused by normal flora of the nasopharynx that ascend the Eustachian tube and enter the middle ear. As OM is a disease of opportunity, it is critical to gain an increased understanding of immune system components that are operational in the upper airway and aid in prevention of this disease. SPLUNC1 is an antimicrobial host defense peptide that is hypothesized to contribute to the health of the airway both through bactericidal and non-bactericidal mechanisms. We used small interfering RNA (siRNA) technology to knock down expression of the chinchilla ortholog of human SPLUNC1 (cSPLUNC1) to begin to determine the role that this protein played in prevention of OM. We showed that knock down of cSPLUNC1 expression did not impact survival of nontypeable Haemophilus influenzae, a predominant causative agent of OM, in the chinchilla middle ear under the conditions tested. In contrast, expression of cSPLUNC1 was essential for maintenance of middle ear pressure and efficient mucociliary clearance, key defense mechanisms of the tubotympanum. Collectively, our data have provided the first in vivo evidence that cSPLUNC1 functions to maintain homeostasis of the upper airway and, thereby, is critical for protection of the middle ear

Foreign bodies in the ears causing complications and requiring hospitalization in children 0-14 age: results from the ESFBI study

The occurrence of foreign bodies (FBs) in otorhinolaryngological practice is a common and serious problem among patients in paediatric age. The aim of this work is to characterize the risk of complications and prolonged hospitalization due to foreign bodies in ears in terms of the characteristics of the injured patients (age, gender), typology and features of the foreign bodies, the circumstances of the accident and the hospitalization's details

A new wide-diameter bone-anchored hearing implant-prospective 1-year data on complications, implant stability, and survival

OBJECTIVE: To investigate a new wide bone-anchored hearing implant considering initial stability, stability over time, implant loss, and skin reaction. STUDY DESIGN: Consecutive, prospective case series. SETTING: Tertiary referral center. PATIENTS: Twenty adult patients were enrolled. All operations were 1-stage, single-incision technique with subcutaneous reduction. INTERVENTION(S): Measurement of implant stability. MAIN OUTCOME MEASURE(S): Implant stability quotient (ISQ) values were recorded using resonance frequency analysis at the time of implantation and at 10 days, 6 weeks, 6 months, and 1 year after surgery. Skin and soft tissue reactions according to Holgers grading system. RESULTS: Implant stability quotient measurements revealed a significant increase in ISQ during the first 10 days after operation, and the ISQ values continued to rise throughout the 1-year observation period. No implants were lost. Skin and soft tissue reactions were rare and minor, as no reaction was seen in 93% of the follow-up examinations and no grade 4 reactions occurred. CONCLUSION: The new wide implant showed good stability at surgery. Osseointegration was fast, and implant stability increased throughout the 1-year observation period. No implants were lost. Skin and soft tissue reactions were rare and minor