Retraction: Volume Fraction of the Human Pathologic Ossicles Destructed by Cholesteatoma Using Micro-CT / 대한이비인후과학회지

No abstract available.

Retraction: Development of the Secretory Elements in the Murine Middle Ear and Eustachian Tube / 대한이비인후과학회지

No abstract available.

Retraction: Study for ReVersibility of Experimental Cholesteatoma Using Mongolian Gerbil / 대한이비인후과학회지

No abstract available.

Retraction: Clinical Characteristics and Diagnostic Classification of Vertigo in Children / 대한이비인후과학회지

No abstract available.

Retraction: The Morphologic Study of Elastic Structures in the Developing Murine Eustachian Tube / 대한이비인후과학회지

No abstract available.

Development of Sentences for Korean Hearing in Noise Test(KHINT) / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Hearing in Noise Test (HINT) is a modified speech reception test using digitally recorded sentences. It is useful in assessing speech communication in noise. This test is easy to set up and to standardize by the commercialized HINT system. We aimed to develop sentences for the Korean HINT system so as to enable international comparative studies. SUBJECTS AND METHOD: Seven hundred fifty natural written sentences were prepared. They were digitally recorded by a professional voice actor, and long-term average spectrum of recorded sentences was calculated for masking noise. The performance-intensity test estimated the relationship between signal-to-noise ratio (S/N ratio) and percent word intelligibility by testing ten normal hearing adults. The next step was to equate the intelligibility of sentences when they were presented in masking noise at a fixed level, and 250 sentences were chosen. Individual phonemes in each sentence were counted after phonemic transcription using international phonemic alphabet. RESULTS: Long-term speech spectrum of Korean sentences showed relatively lower level, especially in high tone, compared to other foreign languages. One dB change of SNR resulted in 9% word intelligibility change. Twenty five lists of ten sentences were formed by adjusting composition of sentences to obtain even phoneme distribution, which were had 9.21.1 syllables. CONCLUSION: Prepared sentences for the Korean HINT will be useful for assessing functional hearing activity as well as international cross-language studies.

Effect of HGF in Invasion of Hypopharyngeal Squamous Cell Carcinoma Cell Line / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Recent reports revealed that hepatocyte growth factor (HGF) is related to tumor invasion and metastasis. Activation of the urokinase-type plasminogen activator (u-PA)/plasmin proteolytic network and matrix metalloproteinase has been shown to play a key role in tumor invasion and dissemination of various malignancies. So we examined the effect of HGF/c-Met on MMP-2, 9 and u-PA in FaDu cell, a hypopharyngeal squamous cell carcinoma cell line. MATERIALS AND METHOD: We performed RT-PCR and Western blot in FaDu. Tumor cell invasiveness was assessed by the membrane invasion assay (using Transwell chamber). To examine the role of MMP-2, 9 and the relation between HGF and MMP in the invasion of hypopharyngeal cancer, RT-PCR and zymography were performed in FaDu cells. We tested to confirm the HGF-mediated plasmin activation. RESULTS: The expressions of c-Met mRNA and protein were detected in the hypopharyngeal cell line while that of HGF was not. HGF markedly enhanced the invasion of cancer cells in a Transwell invasion chamber in a dose-dependent manner (p<0.05). The expression of MMP was detected in hypopharyngeal cancer cells and exogenous HGF slightly enhanced the induction of MMP-2 activity in zymogram analysis. The activity of u-PA was detected in FaDu and HGF (above 10 units/mL) enhanced the activity of u-PA (p<0.05). CONCLUSION: These results suggest that HGF may play an important role in hypopharyngeal cancer through the activation of u-PA and matrix metalloproteinase.

Gene Regulatory Regions Required for beta Defensin-2 Up-Regulation by Interleukin-1alpha in the Human Middle Ear Epithelial Cell Line / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Innate immunity is important in the middle ear because of the lack of immune cells in the region. Among innate immunities beta-defensin-2 is known to play an important role in the immune function of the middle ear. But we still do not understand well about the signal transduction pathway and gene regulatory region of beta-defensin-2 (hBD-2). MATERIALS AND METHOD: The expression of beta-defensin-2 (hBD-2) by IL-1alpha in HMEEC was detected by RT-PCR. The luciferase-expressing vector containing diverse lengths of the hBD-2 5' flanking region made by the progressive unidirectional deletion was transferred to HEEMC (Human Middle Ear Cell). We analyzed the function of 5' flanking region by luciferase activity measured using a luminometer after supplementing corresponding substrates to the cell lysate. RESULTS: hBD-2 was upregulated by IL-1alpha in HMEEC-1. The treatment of IL-1alpha up-regulated the activity of promoter by 7.60+/-1.45 (average+/-standard deviation) folds in 2.7 kpb sized 5' flanking region, 3.81+/-0.78 folds in 1.1 kbp, and 4.00+/-0.73 folds in 500 bp. CONCLUSION: These results indicate there are two effective gene regions that regulate the hBD-2 expression by IL-1alpha between 2.7 kbp and 1.1 kbp, and at 500 bp upstream of the translation starting point of hBD-2 in HMEEC-1.

Clinical Analysis of Hearing Aid Failure / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: An hearing aid is a useful tool for hearing rehabilitation when surgical hearing correction is not indicated. Successful hearing aid rehabilitation is affected by various factors such as the degree and types of hearing impairment, personality, motivation and duration of adaptation. We aimed to identify factors for satisfying hearing aid by analysis and comparison of the successful and the failure groups of hearing aid users, and to recognize problems of hearing aid prescribed in the non-medical institutes. SUBJECTS AND METHOD: Two hundred and sixty six ears of 202 hearing aid users were referred to the Ajou Hearing Center for two years, and their clinical data were retrospectively reviewed including hearing status and hearing aid type. Twenty ears were prescribed by the non-medical institutes and others were 1st time users. The failure group of hearing aid users was defined when they gave up using hearing aid and requested for refund after an adaptation period of more than one month. RESULTS: Hearing aids failed to work in 9% of 266 ears. All problems of previous hearing aid users were solved by represcription and functional modification of hearing aids. The portion of patients older than 65 year old was not different in two groups, but the portion of female patients in the failure group was significantly larger than that in the success group (p=0.01). The unaided speech discrimination score was significantly higher in the success group (p=0.02). The most common cause of hearing aid failure was poor speech discrimination than expectation. CONCLUSION: The speech discrimination score and sex are considered as important factors for successful rehabilitation of hearing aid. The prescription of hearing aids and follow-ups in the experienced medical institutes would predict better outcome. The realization of expectation level is of importance when interviewing hearing aid candidates. Further clinical study is necessary for satisfying hearing aid rehabilitation.

Effect of HGF in Proliferation, Dispersion and Migration of Hypopharyngeal Squamous Cell Carcinoma / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Hepatocyte growth factor (HGF) is known to stimulate motility, invasiveness, proliferation, and morphogenesis of endothelial cells. Recent reports revealed that this growth factor is also related to tumor invasion and metastasis. We examined the role of HGF/c-Met on the proliferation, dispersion and migration of FaDu cell, a hypopharyngeal squamous cell carcinoma cell line. MATERIALS AND METHOD: We performed RT-PCR and Western blot in FaDu. Proliferation of the FaDu cells was assayed by counting the number of cells after treatment by HGF of different concentrations of 0, 10, 30 ng/mL. Dispersion of the cells was observed by measuring the separation and morphologic changes of cells after the colony of FaDu cells was formed in the media and then treated with HGF of 10 ng/mL or 30 ng/mL for 24 hours. Tumor cell migration was assessed by wound healing assay. Lastly, we examined the enhancement of HGF production in human fibroblast (MRC-5) by putative inducer secreted from FaDu cells. RESULTS: The expresssion of c-Met mRNA and protein was detected in the hypopharyngeal cell line while that of HGF was not. Exogenous HGF significantly enhanced the growth of FaDu in a dose-dependent manner 30 ng/ml (p<0.05). HGF stimulated the dispersion and enhanced the migration of cancer cells in a dose-dependent manner (p<0.05). HGF produced by human stromal fibroblast (MRC-5) was increased by a certain inducer originated from FaDu cells (p<0.05). CONCLUSION: These results suggest that HGF may play an important role in the progression of hypopharyngeal cancer through the enhancement of proliferation, dispersion and migration.

Volume Fraction of the Human Pathologic Ossicles Destructed by Cholesteatoma Using Micro-CT / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Conventional studies for the middle ear ossicles destructed by cholesteatoma give relatively limited information on shape, mechanical strength and 3-dimensional relationship. Recently, Micro-CT scanning technology has been applied to analysis of skeletal structure. This study aims to reconstruct the 3-dimensional structure of normal ossicles and destructed ossicles by different cholesteatomas and to compare volume fraction of destructed ossicles with that of normal ossicles. MATERIALS AND METHOD: 13 pathological ossicles obtained during cholesteatoma surgery were used in this study (2 malleuses and 2 incuses from attic cholesteatoma;1 malleus and 2 incuses from sinus cholesteatoma;2 malleuses and 2 incuses from tensa retraction cholesteatoma; 2 incuses from congenital cholesteatoma). As a control, normal ossicles harvested from cadaveric temporal bone specimens were used. The structure of obtained ossicles was analyzed through Micro-CT (SkySan-1072, Belgium) by filming the 2-dimensional cross section image running perpendicular to the long axis of the ossicles. The 3-dimensional images were thereby reconstructed for each, and were analyzed using CT-Analyzer(TM) and ANTTM. Based on the results, the strength of each ossicle were measured. RESULTS: The volume fraction, indicating relative strengths of ossicles, was lower in the portion of destructed surface. The pattern of destructed ossicles by cholesteatoma was different according to pathological status of cholesteatoma. CONCLUSION: Our preliminary data of ossicular structure analyzed by Micro-CT scan will be helpful for elucidation of pathological ossicles in middle ear cholesteatoma and will make a great contribution to research of middle ear cholesteatoma.

Expression of beta Defensins in the Human Middle Ear Mucosa / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: It is believed that the innate immunity plays a critical role in protecting the tubotympanum from being infected because the middle ear cavity is normally sterile despite of a paucity of immune cells. Among known antibacterial molecules, defensins have been shown to contribute significantly to innate immunity. However, it is still unclear whether or not beta defensins are expressed in human middle ear mucosa. MATERIALS AND METHOD: Immunolabeling and RT-PCR were performed with the mucosal specimen from normal subjects and otitis media patients, respectively. Expression of beta defensin 2 mRNA was compared between the control group and experimental group that was treated by inflammatory stimuli in the animal models using RT-PCR. RESULTS: beta defensin 1 was expressed in both normal and inflamed middle ear mucosa of human, but beta defensin 2 and 3 were found only in the inflamed mucosa. The expression of beta defensin 2 mRNA was up-regulated when the interleukin-1alpha (IL-1alpha) or lipopolysaccharide (LPS) was treated in the middle ear mucosa of the experimental animals. CONCLUSION: We could show that beta defensins are expressed in the human middle ear mucosa and that beta defensin 2 is up-regulated by the inflammatory stimuli, IL-1alpha or LPS.

Proposal for Classification of Isolated Congenital Ossicular Anomalies / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: There are many different types of congenital ossicular anomalies, which may be broadly divided into major ear anomalies and minor ear anomalies. Minor congenital anomalies are restricted to the middle ear, while major congenital anomalies are malformations of the middle ear and external meatus and sometimes the auricle. The great diversity of anomalies of the middle ear described in the literature makes it difficult to compare and analyze it. The objective of this study is to review and analyze the isolated congenital ossicular anomalies published in the Korean literatures with special reference to the pattern of anomalies and surgical treatment results, and to propose a new systematic classification of isolated congenital ossicular anomalies. SUBJECTS AND METHOD: We reviewed retrospectively 10 Korean literatures concerning isolated congenital ossicular anomalies, which included 117 cases. We also reviewed 9 cases of isolated congenital ossicular anomalies from Ajou University Hospital from Jan 2002 to June 2003, which were not reported in the literature. Among the total 126 cases of isolated congenital ossicular anomalies, follow-up on the hearing results was possible in 112 ears. RESULTS: We proposed a new classification of isolated congenital ossicular anomalies using 5 types based on the stapes status. Twenty-six anomalous patterns were detected out of 126 cases of isolated congenital ossicular anomalies. Using the new classification, the more severe anomaly stapes could be displayed, and the worse postoperative hearing gain could be also predicted. CONCLUSION: Ossicular anomalies were detected without a certain rule of pattern, and big variety of those patterns could be detected in the future. Our proposed new classification will be helpful to analyze the pattern and surgical result of congenital ossicular anomalies.

A Case of Cochlear Implantation in a Postlingual Deaf Patient with Behcet Disease / 대한이비인후과학회지

Recurrent iritis and oral/genital ulcers have been described for the first time as a separate pathological entity by the Turkish dermatologist Hulusi Behcet. Behcet disease is a chronic, multi-systemic disorder, which affects many organs as a result of vasculitis. The clinical manifestations are divided into two groups: major (oral ulcers, eye lesions, genital ulcerations, and skin lesions) and minor (arthritis, gastrointestinal lesions, epididymitis, thrombophlebitis, and central nervous system involvement) criteria. The incidence of hearing loss in Behcet disease has been reported as 12% to 80% in several studies. A 37-year-old man diagnosed as Behcet disease was admitted to our department with complaints of profound right hearing loss and dizziness. He was treated with steroid without improvement. After one year, he suffered from complete hearing loss on the left side. A temporal bone CT scan revealed right cochlear ossification. Cochlear implantation was performed within 4 weeks after the completion of steroid therapy in the left cochlea, which was partially obstructed by fibrotic tissue. However, the electrode was fully inserted without resistance. Wound healing complications were not encountered in the postoperative period. The hearing threshold was restored to 30 dBHL, while speech discrimination did not improve as much as expected. We propose that the routine hearing examinations be employed in the evaluation and management of Behcet disease. According to our experience, we find that cochlear implantation should be carried out at an early stage, before the development of labyrinthine ossification.

Conservation of Mucous Epithelial Characteristics in the Human Middle Ear Epithelial Cell Line / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: The stable cell line system of middle ear epithelial cells is essential for studying molecular pathogenesis of otitis media. Recently, we succeeded in establishing the human middle ear epithelial cell line (HMEEC) using a retrovirus. The cell line retains many of the phenotypic and morphological properties of the non-transformed, parental cultures such as the expression of cytokeratin and tight junctions. We aimed to show the conservation of mucosal characteristics and subcellular mechanisms of transcriptional regulation in this cell line. MATERIALS AND METHOD: RT-PCR was performed using mucin gene specific primers and total RNA extracted from HMEEC. The luciferase-expressing vector containing 5' flanking region of human beta defensin 2 (hBD-2), an inducible antimicrobial peptide, was transfected to HMEEC. After starvation of serum, HMEEC was treated with interleukin 1 alpha (IL-1alpha) and subsequently harvested 10 hrs later. Luciferase activity was measured using luminometer after the corresponding substrate was supplemented to the cell lysate. RESULTS: Expression of mucin genes (MUC1, 2 and 5B) in HMEEC was demonstrated by RT-PCR. Luciferase assay showed that IL-1alpha up-regulates the promoter activity of hBD-2 more than 10 fold. This transcriptional regulatory mechanism was also demonstrated in the well established reference cell lines, HeLa cells and A549 cells. CONCLUSION: We demonstrated the conservation of mucin gene expression and transcriptional regulatory mechanism of hBD-2 in HMEEC. The proposed cell line can serve as a useful experimental model for elucidating the pathogenesis of middle ear mucosa-related diseases.

Expression of HGF/c-Met in Hypopharyngeal Squamous Cell Carcinoma / 대한이비인후과학회지

Hepatocyte growth factor (HGF), a potent stimulator of hepatocyte growth, stimulates motility, invasiveness, proliferation, and morphogenesis of epithelium, and may be involved in physiologic and pathologic processes such as embryogenesis, wound healing, organ regeneration, inflammation, and tumor invasion. So we examined the role of the HGF/c-Met on invasion and metastasis of hypopharyngeal squamous cell carcinoma (SCC). We performed immunohistochemical stains on 40 normal mucosas and 40 SCCs of hypopharynx with HGF antibody and c-Met antibody. For RT-PCR and Western blot, fresh normal tissues and cancer tissues in hypopharynx obtained from five patients were used. The positive rates of HGF and c-Met expression in hypopharyngeal SCC were 77.5% and 70%, respectively. HGF staining was significantly correlated with lymph node metastasis and pathologic stage (p<0.05). c-Met staining was only significantly correlated with lymph node metastasis (p<0.05). The increased expresssion of c-Met mRNA (RT-PCR) and protein (Western Blot) were detected in hypopharyngeal cancer tissue. These results suggest that HGF may play an important role in the progression of hypopharyngeal cancer.

Three Cases of Waardenburg Syndrome Type 2 in a Korean Family

Waardenburg syndrome (WS) is a rare, autosomal dominant disorder characterized by sensorineural hearing loss, pigmentary disturbances of the skin, hair, and iris, and other developmental defects such as lateral displacement of both medial canthi and lacrimal puncta called dystopia canthorum. While mutations of the PAX3 (paired box) gene have been identified in about 99% of WS type 1 cases, WS type 2 is a heterogeneous group, with about 15% of cases caused by mutations in microphthalmia associated transcription factor (MITF). We have experienced three cases of typical WS type 2 in a Korean family, for whom full ocular examination and genetic studies were performed. The genetic studies revealed no mutation in either PAX3 or MITF genes. The genetic basis, as yet unknown for most cases of WS type 2, might be found with further investigation.

Clinical Follow-up of Hearing-Impaired Infants Detected by Newborn Hearing Screening / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: When screened using cord blood, congenital hearing loss are detected more frequently than other congenital metabolic diseases such as phenylketonuria or congenital hypothyroidism. Newborn hearing screening is important because the early identification and intervention of neonatal hearing loss is beneficial for the language development. We aimed to analyze clinical characteristics including associated diseases and present hearing state, and the effects of speech rehabilitation in the hearing-impaired infants detected by newborn hearing screening program of Ajou University Hospital. SUBJECTS AND METHOD: Seventy nine hundred twelve neonates (6915 well babies and 997 NICU babies) were screened by transient evoked otoacoustic emission (TEOAE) and auditory brainstem response (ABR). Medical records of infants with bilateral hearing loss of more than 60 dB were evaluated, and they were further studied with temporal bone CT scan and follow-up hearing tests using ABR. The exon2 of the connexin26 gene was sequenced to detect the mutation. RESULTS: Fourteen of 7912 infants initially had bilateral hearing loss of more than 60 dB. Associated diseases were prematurity, hyperbilirubinemia, sepsis, low birth weight, chromosomal anomaly, cleft palate, congenital nevus, and congenital aural atresia. Three of 14 infants were revealed to have normal hearing after follow-up hearing test, which were associated with cleft palate, hyperbilirubinemia or prematurity. One of them had 235delC mutation of the connexin26, and the temporal bone CT scan demonstrated the finding of enlarged vestibular aqueduct syndrome (EVAS) in one infant. Two infants participated in the connected speech rehabilitation program and showed significant development of language. CONCLUSION: Follow-up hearing tests are important in case of failures of newborn hearing screening test. The establishment of auditory and speech rehabilitation program connected with newborn hearing screening is essential in treating hearing-impaired neonates.

Treatment Effects of Glutamate Antagonist for Tinnitus / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Tinnitus is one of the most widespread disorders of the auditory system, affecting approximately 17% of the general population, with the frequency increasing to about 33% in the elderly. However, little is known about the underlying physiological mechanism that causes tinnitus and there is no definite treatment. Recently, several studies have showed that subjective tinnitus is mostly generated at the synapse between inner hair cells and their afferent nerves and in addition, some have showed that glutamate is likely to act as the neurotransmitter. The aim of this study has been to evaluate the effective use of caroverine hydrochloride and memantine hydrochloride for tinnitus treatment and to determine their appropriate indication of glutamate antagonist therapy. MATERIALS AND METHOD: From May 1998 through June 2000, 188 patients with subjective tinnitus were treated with caroverine hydrochloride (Spamon(R)). Of the patients, 153 were followed, and 20 of these patients who did not respond to caroverine hydrochloride were treated additionally with memantine hydrochloride (Akatinol(R)). Audiological evaluations were performed in all of the patients. Pre and post-treatment status was analyzed by handicap inventories. RESULTS: Subjective tinnitus was improved in 55 (35.9%) of 153 patients who were treated with caroverine hydrochloride and 11 (55.0%) of 20 patients with memantine hydrochloride. The response group had tendency of shorter duration history of tinnitus than the non-response group. There was no difference between the response group and the non-response group in age, sex, site, and tinnitus characteristics. CONCLUSION: We suggest that glutamate antagonists such as caroverine hydrochloride and memantine hydrochloride can be used as an alternative modality for treatment of subjective tinnitus.

Study for Reversibility of Experimental Cholesteatoma Using Mongolian Gerbil / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Epidermal characteristics of cholesteatoma such as invasion, migration, uncoordinated proliferation, and altered differentiation may arise as a result of defectiVe wound healing process, induction of preneoplastic transformation or genetic alteration. To date, a number of genes haVe been shown to be differentially regulated in cholesteatoma, which might be responsible for these clinical characteristics. HoweVer, it is still unclear whether these phenomena is only oVert when cholesteatoma is under specific conditions such as inflammation or infection. If these genetic alterations in the deVelopment of cholesteatoma are transient, the pathology of cholesteatoma may be reVersible. We hypothesized that once cholesteatoma is in the normal environment, the cellular or molecular pathology of cholesteatoma can return to normal epidermal characteristics. The aim of this study was to determine whether common molecular characteristics are reVersible or not after removal of inductive factors in aural cholesteatoma induced gerbils. MATERIALS AND METHODS: We induced canal ligation cholesteatoma using Mongolian gerbils. The treated group was untied and managed for 2 weeks. We examined differences between treated cholesteatoma and untreated cholesteatoma by using a TUNEL staining and immunohistochemical technique with proliferation markers (PCNA, cytokeratin 13/16). RESULTS: With PCNA and CK 13/16, untreated group showed positive staining in the suprabasal cells as well as in the basal cells, but the treated group showed weakly positive staining only in the basal cell layer. With TUNEL staining, positive cells increased more in the untreated group than in the treated group. CONCLUSION: These results encourage our belief that some cholesteatomas, especially cholesteatoma in early stages, might be managed with only minimal treatments such as control of inflammation and maintenance of adequate Ventilation.