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| 1994 | ||||
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Cytokeratin immunohistochemistry of congenital cholesteotoma in the middle ear The 17th Midwinter Meeting of Association for Research in Otolaryngology; St. Petersburg , U.S.A.: Feb 6-10, 1994 Identificaction and classification of different cytokeratins (the intermediate-sized filaments distinctive of epithelial cells) have been substantially improved by the use of monoclonal antibodies. The actual detailed cytokeratins composition in a given epithelial cell varies in relation to cell type, growing environment, stage of development, differentiation, and disease condition, and shows great specificity and stability. It appeared to us that an investigation into the characteristics of epithalia involved in the genesis of cholesteatoma, as made possible by the monoclonal antibodies technique, might result in some useful contributions to the solution of classical problems concerning the nature and origin of middle ear cholesteatomas. In this study, we investigated cytokeratin expression of congenital cholesteatoma to compare with that of acquired cholesteatoma, using immunohistochemical technique with five subtypes of monoclonal anti-epithelial keratin (ICN Immuno Biologicals, Costa Mesa , CA). The expression of the cytoskeletal protein from the mesenchymal cell origin, vimentin, was also studied. The cholesteatoma matrix and ear canal skin were obtained by surgery from one patient from external ear canal cancer whose middle ear mucosa was normal. Similarity of cytokeratin patterns were observed among congenital cholesteatoma, acquired cholesteatoma and ear canal skin. Several differences of cytokeratin patterns were observed between cholesteatoma and middle ear mucosa. These findings support the skin type epithelial origin of congenital cholesteatoma and strongly favor the immigration theory in the genesis of cholesteatoma. Cytokeratin immunohistochemistry of open cavity mastoidectomized skin The 4th International Academic Conference on Immunobiology in Otology, Rhinology and Laryngology; Oita, Japan : Apr 4-7, 1994 Cavity problems which can develop after an open cavity mastoidectomy have received much attention in the field of otology. One of the cavity problems is that squamous debris accumulates in the ear canal which occasionally causes some troubles. Lately, morphology of this newly formed skin in the open-mastoidectomized cavity (cavity skin) was partly investigated to compare with that of cholesteatoma matrix. Identification and classfication of different cytokeratins (the intermediate-sized filaments distinctive of epithelial cells) have been substantially improved by the use of monoclonal antibodies. The actual detailed cytokeratin composition in a given epithelial cell varies in relation to cell type, growing environment, stage of development, differentiation, and disease condition, and shows great specificity and stability. It appeared to us that an investigation into the characteristics of epithelia involved in the genesis of cholesteatoma, as made possible by the monoclonal antibodies technique, might result in some useful contributions to the solution of classical problems concerning the nature and origin of middle ear cholesteatomas. The aim of this study was to compare the cytokeratin pattern of cavity skin with that of middle ear cholesteatoma and ear canal skin and to search the pathogenesis of cholesteatoma. In this study, we investigated cytokeratin expression of cavity skin, cholesteatoma and ear canal skin, using immunohistochemical technique with five subtypes of monoclonal antiepithelial keratin (ICN ImmunoBiologicals, Costa Mesa , CA). Similarity of cytokeratin patterns was observed among cavity skins, middle ear cholesteatomas and ear canal skins. These findings support the skin type epithelial origin of cholesteatoma and strongly favor the immigration theory in the genesis of cholesteatoma. Clinical experience of a new combined therapy of laser and ginkgo-extract on tinnitus and sudden deafness. The 5th Japan-Korea Joint Meeting of Otolaryngology-Head and Neck Surgery; Kyongju , Korea: Apr 29, 1994 Tinnitus and sudden deafness are frequently encountered with various kinds of etiology in clinical practice. Many treatment protocols about these diseases have been introduced until now, but they did not make us satifiable. A new combined therapy of Laser and Ginko-Extract was tried to 40 patients with tinnitus and 20 patients with sudden deafness. The rationale of this trial is reactivation of decreased cell metabolism by stabilizing vascular wall, washing out toxic materials from blood and gene activation. The purpose of this study is to analyse the clinical results of this trial and to provide the basic data for application of this therapy as a new treatment modality on inner ear disorders. Treatment with this trial had relatively good results even though all cases had already treatment failure with ordinary methods. Cholesteatoma in the middle ear: review of its pathogenesis. The 5th Japan-Korea Joint Meeting of Otolaryngology-Head and Neck Surgery; Kyongju , Korea: Apr 29, 1994 Congenital cholesteatoma of the middle ear is a rare clinical entity that classically presents as a pearly epidermal cyst seen behind the normal tympanic membrane. Many otologist have speculated on the pathogenesis of congenital cholesteatoma (Lack of tympanic ring, epithelal inclusions resulting from invagination of otic capsule or from defective closure of the neural tube, metaplasia, epidermoid formation), but lack of further study has been due mainly to the rarity of this abnormality. In this study, we reviewed 4 cases of congenital cholesteatoma to determine its pathogenesis by analysing findings of operation and temporal bone computed tomography. This review supports Lack of tympanic ring theory (Aimi, 1983) as proposed mechanism of congenital cholesteatoma, and storongly favors abberant migration of squamous epithelium from a distant source in the genesis of congenital cholesteatoma. Lectin binding patterns of open cavity mastoidectomized skin. The 98th Annual Meeting of American Academy of Otolaryngology-Head and Neck Surgery; San Diego, U.S.A. : Sep 18-21, 1994 Cavity problems which can develop after open cavity mastoidectomy have received much attention in the field of otology. One of the cavity problems is that squamous debris accumulates in the ear canal which occasionally causes some troubles like cholesteatoma. Lately, morphology of this newly formed skin in the open-mastoidectomized cavity (cavity skin) was partly investigated to compare with that of cholesteatoma matrix. Glycoconjugates play an important role in cell recognition, differentiation and growth control in many normal and malignant tissues. The epidermis of human skin can be considered as a multilayered organ in which undifferentiated basal cell undergo stepwise maturation, migrating into the upper cell layers. During this differentiation process, expression of glycoconjugate on the keratinocyte membrane alters in each epidermal layer, and many authors reported that alteration of cell surface glycoconjugates in the human epidermis can be dectected as a differential lectin-binding specificity. Lectins are carbohydratebinding proteins of a nonimmune nature that agglutinate cells or precipitate polyssacharides of glycoconjugates. The carbohydrate- binding specificity of lectins is comparable to that of enzymes, and lectins can therefore act as a probe to localize different carbohydrate moieties. Through the use of lectins, a detailed analysis can be made of carbohydrate residues present on epithelial cell surfaces. In this study, we investigated lectin-binding patterns of cavity skin to verify its differentiating characteristics by comparing with those of cholesteatoma matrix and postauricular skin, using cytochemical technique (ABC method) with seven types of biotinylated lectins (Vector Lab., Burlingame, CA). In general, similarity of lectin-binding patterns was observed among cavity skin, middle ear cholesteatoma and postauricular skin, but some lectins had the difference between cavity skin and cholesteatoma. We suggest that there is a lack or modification of certain carbohydrates in the cavity skin, and this might account for the characteristic differences between cavity skin and cholesteatoma. |
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| 1995 | ||||
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Cytokeratin expression in experimental cholesteatoma of gerbil. The 18th Midwinter Meeting of Association for Research in Otolaryngology; St. Petersburg , U.S.A.: Feb 5-9, 1995 Cholesteatoma is characterized by the presence of a keratinizing epithelium in the middle ear. It is thought to be derived from ingrowth of the migratory keratinocytes of the epidermis covering the tympanic membrane and deep external ear canal. Also, the accumulation of desquamous epithelial cells appears to be a crucial factor in the pathogenesis of the middle ear proliferation, and differentiation of basal keratinocytes. In the present study, we examines the expression of the specific cytokeratins in the normal and cholesteatomatous meatal epithelium of Mongolian gerbil for a better understanding of the state of differentiation and proliferation of cholesteatoma. Similarity of cytokeratin patterns was observed among cholesteatoma, deep meatal skin and other epidermis. However, cholesteatoma showed more hyperproliferation and some variations of the differetiation. Also, some nonepidermal cytokeratin sets were present in cholesteatoma and normal meatal epithelium. lmmunohistochemical study on cytokeratin expression in experimental cholesteatoma. The 6th International Symposium on Recent Advances in Otitis Media; Ft. Lauderdale , U.S.A.: Jun 4-6, 1995 Cholesteatoma is characterized by the presence of a keratiniz 35 ing epithelium in the middle ear which is frequently accociated with chronic otitis media. The pathogenesis of cholesteatoma is still unknown. Several laboratory animals have been used as a model of cholesteatoma formation. This experimental approach is of interest because it can potentially provide new information on cholesteatoma pathogenesis in response to chronic middle ear inflammation. Identification and classification of different cytokeratins (the intermediate sized filaments distinctive of epithelial cells) have been substantially improved by the use of monoclonal antibodies. The actual detailed cytokeratin composition in a given epithelial cell varies in relation to cell type, growing environment, stage of development, differentiation, and disease condition, and shows great specificity and stability. It appeared to us that an investigation into the characteristics of epithelia involved in the pathogenesis of cholesteatoma, as made possible by the monoclonal antibodies technique, might result in some useful contributors to the solution of classical problems concerning the nature and origin of middle ear cholesteatoma. In this study, we induced cholesteatoma in two groups of Mongolian gerbil: One is by surgical ligation of the external auditory canal and the other is by implanting ear canal skin in the otic bulla. Using immunohistochemical technique with several subtypes of anticytokeratin monoclonal antibodies, we investigated cytokeratin expression of two groups of experimental cholesteatoma to compare with that of the ear canal skin and middle ear mucosa of Mongolian gerbil. These results indicate that the cellular differentiation in normal deep meatal skin may be maintained in induced cholesteatoma. Also, this finding indicates the hyperproliferative characteristic of deep meatal skin of the gerbil. Myringoscopic findings of the skull base tumors. The 3rd Asian-Oceanian International Congress on Skull Base Surgery; Seoul , Korea: Nov 2-3, 1995 Some skull base tumors involving the temporal bone present as a middle ear cavity mass. This shows through the intact tympanic membrane, and also represents the otological symptoms such as hard of hearing, tinnitus and facial palsy. By photographing the tympanic membrane, we analysed the occurrence of 16 cases of the tumorous lesions (2 facial nerve tumors, 1 vagus nerve tumor, 1 trigeminal nerve tumor, 2 glomus tumors, 2 high jugular bulbs, 4 congenital cholesteatomas, 4 cholesterol granulomas) in the temporal bone according to four quadrants of the tympanic membrane. Radiographic materials (temporal bone CT and MRI) were included for clarifying the ear drum findings. The purpose of this study was to familiarize the neurotologist with the eardrum findings of the tumourous lesion in the temporal bone. A surgical results of nasopharyngeal carcinoma. The 3rd Asian-Oceanian International Congress on Skull Base Surgery; Seoul , Korea: Nov 2-3, 1995 A retrospective analysis of therapeutic results of 9 cases of nasopharyngeal carcinoma was conducted. All case received radiation therapy preoperatively and followed more than 6 months. 1) Tumors with stage III (n=2), stage IV (n=7) were included in this study and had the adenoid cystic carcinoma (n=1), squamous cell carcinoma (n=4), undifferentiate cell carcinoma (n=4). 2) The surgical techniques used were infratemporal fossa approach type C (n=6), maxillary swing technique (n=2), facial translocation technique (n=1). 3) Two cases had incomplete resection and two cases had distant metastasis and one died with disease. 4) Four cases were no evidence of disease, two cases were alive with disease, two cases died of disease and one case was dead without disease. Complete resection has the limitation in cases invading to the carvernous sinus. Preoperative comprehensive therapeutic planning is required to get the satisfactory result. |
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| 1996 | ||||
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Hyperproliferative characteristics of human middle ear cholesteatoma. The 19th Midwinter Meeting of Association for Research in Otolaryngology; St. Petersburg , U.S.A.: Feb 4-8, 1996 Human epidermis is a continously dividing tissue, in which keratinocytes gradually differentiate and maturate while moving from basal cells to suprabasal cell layers. In normal epidermis, the expression of cell surface saccharides appeared to be related to the stage of cellular differentiation, and keratinocytes in different cell layers excess different terminal saccharides. Cholesteatoma is characterized by the presence of a squamous epithelium invading the middle ear, which is believed to have hyperproliferative properties. The hyperproliferative character of cholesteatoma epithelium was confirmed through hyperproliferation- associated cytokeratin expression (Sasaki and Huang. Otolaryngol Head Neck Surg 1994 ;110: 310-7). The aim of this study was to determine whether the hyperproliferative character of cholesteatoma is associated with high capacity of keratin synthesis of basal cells or associated with hyperproliferative suprabasal cells. Using immunohistochemical technique with anticytokeratin monoclonal antibodies (proliferating and basal cell markers), we investigated cytokeratin expression of human middle ear cholesteatoma to compare with that of the postauricular skin. We also investigated lectin-binding to N-acetylgalactosamine (Dolichos biflorus agglutini) of cholesteatoma to verify its differetiating characteristics. These results suggest that hyperkeratinization in cholesteatoma may not be due to hyperproliferation of basal cell compartment, but may rather be caused by proliferative suprabasal compartment. Clinical features of ear canal cholesteatoma in children. 6th Japan- Korea Joint Meeting of Otolaryngology ; Morioka, Japan : May 9, 1996 In recent years there has been an increasing number of case reports and an apparent increase in interest in ear canal cholesteatoma, especially in children. The aim of this study is to describe clinical characteristics of ear canal cholesteatoma in children, and to compare them with those of ear canal cholesteatoma in adults. In this study, we reviewed 6 cases of child canal cholesteatoma and 10 cases of adult ear canal cholesteatoma by analyzing findings of myringoscopy, operation and temporal bone computed tomography. This review supports that the lesion in child ear canal cholesteatoma is more extensive than in adult ear canal cholesteatoma. Immunohistochemical detection of proliferating cell nuclear antigen in experimental cholesteatoma 1996 Sendai Ear Symposium; Sendai , Japan: May 11, 1996 Human cholesteatoma in the middle ear is characterized by the presence of a keratinizing epithelium which is believed to have hyperproliferative properties. The pathogenesis of cholesteatoma including its hyperproliferative characteristic is still unknown. Several laboratory animals have been used as model of cholesteatoma formation. This experimental approach is of interest because it can potentially provide new information on cholesteatoma pathogenesis. Among the various approaches for evaluating the proliferative activity, proliferating cell nuclear antigen (PCNA) has been recently introduced as an antigenic marker of cellular proliferation. PCNA is 36KD nuclear antigen which appears at S and G1 phases in cell cycle. Proliferating cell can be detected using anti-PCNA antibody. In this study, we induced the aural cholesteatoma by surgical ligation of the external auditory canal in Mongolian gerbils. Using immunohistochemical technique with anti-PCNA monoclonal antibody (PC10; Novocastra Lab. , United Kingdom ), we investigated mitotic activity of experimental cholesteatoma epithelium to verify its hyperproliferative characteristic by comparing it with that of the ear canal skin. Congenital cholesteatoma in the middle ear which can cause acquired cholesteatoma: fact or fancy. 5th International Conference on Cholesteatoma and Mastoid Surgery; Algehro , Italy: Sep 2, 1996 Congenital cholesteatoma of the middle ear is a rare clinical entity that classically presents as a pearly epidermal cyst seen behind the normal tympanic membrane. In recent years there has been an increasing number of case reports and an apparent increase in interest in congenial cholesteatoma in the middle ear. The actual incidence of congenital cholesteatoma is substantially greater than the literature indicates. Several otologists have speculated on the pathogenesis of congenital cholesteatoma but to date pathogenesis of acquired cholesteatoma related to congenital origin has been sketchy. In this study, we reviewed 8 cases of congenital cholesteatoma including 5 suspicious cases to determine whether congenital cholesteatoma may also be a source of acquired cholesteatoma by analyzing findings of myringoscopy, operation and temporal bone computed tomography. This review supports that some acquired cholesteatoma in the middle ear may have the possibility of congenital origin. Epithelial mitotic activity of induced aural cholesteatoma in Mongolian gerbil. 5th International Conference on Cholesteatoma and Mastoid Surgery; Algehro , Italy: Sep 2, 1996 Mongolian gerbil is well known to form aural cholesteatomas. This animal model is useful to study changes in the keratinizing epithelium. Ligation of external auditory canal of the Mongolian gerbil stimulates the spontaneous development of cholesteatoma in that keratin egress from the ear canal blocked. But it is still obscure whether keratin accumulation can increase the proliferative activity of the keratinizing epithelium in tympanic membrane and deep meatal skin. In this study, the proliferation of the epidermis in the various areas of the ear canal including tympanic membrane in normal gerbil, was investigated using monoclonal anti-5-bromo-2-deoxiuridine (BrdU) to detect intraperitoneally injected BrdU. Also cell prolifer 37 ation of the epidermis in the induced aural cholesteatoma at various stages was monitored using the same antibody. Deep meatal epidermis and some annular area in normal gerbil showed unusual proliferative capacity. Also the induced aural cholesteatoma showed more active generation of epithelial cell. These observation suggested that extensive accumulation of the keratinous mass in the external meatus might induce the change in cellular differentiation and proliferation. The management of extensive juvenile anigiofibroma with facial translocation approach. The 2nd International Skull Base Congress; San Diego , U.S.A. : Jun 29 - Jul 4, 1996 The management of large juvenile nasopharyngeal angiofibroma with intracranial extension is controversial. The author reports two cases of extensive juvenile nasopharyngeal angiofibroma invading the cranial base. The diagnostic and treatment approach consisted of preoperative MRI, embolization of the feeding vessels from the external carotid artery, as well as intratumoral embolization of the feeding branches from the internal carotid artery. Complete tumor resection was attempted using the facial translocation approach. Intraoperative and postoperative complications were minimal. In the author experience, this therapeutic strategy is a safe method for extensive nasopharyngeal angiofibroma. Chondromyxoid fibroma of the jugular fossa invading the posterior cranial base. The 2nd International Skull Base Congress; San Diego , U.S.A. : Jun 29 - Jul 4, 1996 The authors describe a case of chondromyxoid fibroma of the jugular fossa extending along the posterior cranial base in a 40-year-old woman. The presence of this tumor was heralded only by pulsatile tinnitus. The tumor arose from the jugular fossa, eroding the mastoid cavity, and invading the infra-labryrinthine portion of the petrous bone and posterior cranial base. The incidence of these tumors is extremely rare, and, to the fossa. The clinical appearance of this tumor and its pathological findings were presented with reference to other articles. A surgical results of nasopharyngeal carcinoma. The 2nd International Skull Base Congress; San Diego , U.S.A. : Jun 29 - Jul 4, 1996 A retrospective analysis of therapeutic results of ten cases of nasopharyngeal carcinoma was conducted. All cases received radiation therapy preoperatively and were followed for more than six months. Tumors with stage III (n=2) and stage IV (n=7) were included in this study and had adenoid cystic carcinoma (n=2), squamous cell carcinoma (n=4), or undifferentiated cell carcinoma (n=4). The surgical techniques used were the infratemporal fossa approach type C (n=6), maxillary swing technique (n=2), and facial translocation technique (n=1). Two cases had incomplete resection, two cases had distant metastasis, and one died of disease. In four cases there was no evidence of disease, three cases are alive with disease, two cases died of disease and one case died without disease. Preoperative comprehensive therapeutic planning is required to obtain a satisfactory result. Clinical study of levofloxacin treatment of acute infectious disease in ENT field. The 5th Western Pacific Congress on Chemotherapy and Infectious Diseases; Singapore : Dec 2-4 , 1996 This study was carried out to evaluate the efficacy of levocabastine, a new topical antihistamine, in the treatment of allergic rhinitis. The total 264 child and adult patients with symptoms and signs of allergic rhinitis and positive skin reactions were included in this study. Nasal symptoms with a scale of 4 were recorded daily with diary cards for two weeks. The treatment efficacy were globally assessed at the end of clinical trials. The onset of symptom relief was observed within 15 minutes in 77% of patients. There was excellent or good symptomatic improvement in 61% of patients. The adverse effects were insignificant. The results of this study suggest that levocabastine may be effective in the treatment of allergic rhinitis without significant side effects. |
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| 1997 | ||||
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Ossicular disruption after head trauma. The 16th World Congress of Otorhinolaryngology-Head & Neck Surgery; Sydney , Australia: Mar 2-7, 1997 Mechanization and reliance on motorized transportation place everyone in our society at risk for head injury. Temporal bone trauma is usually the result of blunt head injury in patients suffering from multiple body injury. So hearing problem can be neglected initially. But many patients complain hard of hearing immediately or later. By Schuknecht and Davision (1953), hearing loss after head trauma can develop with or without temporal bone fracture. The aim of this study was to analyze the types of ossicular disruption after head trauma and to review their pathophysiology. In the present study, we analyzed 23 cases of ossicular disruption after head trauma (mean age: 20.0 years, M:F = 3:2) which diagnosis was based on history, physical examination, findings of temporal bone computed tomography and confirmed with operative findings. Incus dislocation which was divided into two groups (complete and incomplete) was the most common type of the ossicular disruptions. Second most common type was incudostapedial joint separation. In 8 cases, there was no visible temporal bone fracture line. These findings propose that ossicular disruptions can occur with or without temporal bone fracture line, and mechanisms of ossicular disruption are effect of concussion, effect of inertia, tetanic contraction of intratympanic muscles, twisting effect, and torsion effect. Incus has no muscular anchor and has the weakest soft tissue attachment among all ossicles, so it is possible that incus can be dislodged easily with or without skull fracture. Comparison of nicotinic acetylcholine receptor subunit a 9 between rat and guinea pig. Sendai Ear Symposium 97; Sendai, Japan : Apr 20, 1997 We determined the guinea pig alpha 9 cDNA sequence from the guinea pig organ of Corti cDNA library. The guinea pig and rat alpha 9 cDNA sequence are similar at both nucleotides transmembrane segments 3 and 4. These changes could account for the different responses to the agonist DMPP reported for rat and guinea pig outer hair cells. Clinical characteristics of middle ear cholesteatoma in children related to its pathogenesis. The 3rd Extraordinary International Symposium on Recent Advances in Otitis Media; Copenhagen , Denmark: Jun 1-5, 1997 Cholesteatoma occuring in childhood is often said to be more aggressive than that seen in adults. Charachon (1985) attributes this to the greater growth potential of tissues in childhood, along with common secondary infection and progression of the normal evolution of mastoid pneumatization that offers less resistance to the cholesteatoma. In these sense, the pathogenesis of children cholesteatoma can be suspected to be different from that of adults cholesteatoma. The purpose of this study is to investigate the clinical characteristecs of cholesteatoma in children by comparing them with those of adults cholesteatoma, and eventually to search the pathogenesis of children cholesteatoma different from that of adults cholesteatoma. In present study, we reviewed 30 cases of children cholesteatoma and compaired them with 157 cases of adults cholesteatoma by analysing drum finding, cholesteatoma extent, ossicular destruction status, complication and temporal bone pneumatization of both two groups. Children cholesteatoma, when compared with adults cholesteatoma, had more variable ear drum findings, less suppressive pneumatization of the mastoid air cells, more extensive in intraoperative finding, different ossicular destruction patterns and rarely occurred complications. These findings proposed us to search the possibility that the pathogenesis of children cholesteatoma can be different from that of adults cholesteatoma. Pathogenesis of cholesteatoma. The 1st China-Korea Medical Conference; Beijing, China : Jul 8-10, 1997 In spite that cholesteatoma in the middle ear is one of the most important diseases in otological field, its pathogenesis has had a long discussion which has not ended yet. All theories published so far can be divided into two main groups: epidermal theory, in situ theory. All theories that belong to epidermal theory assume that the origin of the cholesteatoma must be sought in the existing epidermal lining of the ear durm or external auditory canal. How this epidermis invades the middle ear cleft is explained by three main concepts, namely the migration theory, the retraction theory and the proliferation theory. The hypotheses that can be assigned to in situ theories have the view that the site of origin of the cholesteatoma was located within the temporal bone. The two main concepts are the congenital and metaplasia theories. In recent years there has been an increasing number of case reports and an apparant in crease in interest in the middle ear congenital cholesteatoma. The actual incidence of congenital cholesteatoma is substantially greater than the literature indicates. I reviewed a number of cases of the middle ear cholesteatoma which supports that some acquired cholesteatoma in the middle ear may have the possibility of congenital origin. Hyperproliferation of middle ear cholesteatoma. The 1st China-Korea Medical Conference; Beijing, China : Jul 8-10, 1997 Human epidermis is a continuously dividing tissue, in which keratinocytes gradually differentiate and maturate while moving from basal cells to suprabasal cell layers. In normal epidermis, the expression of cell surface saccharides appears to be related to the stage of cellular differentiation, and keratinocytes in 39 different cell layers express different terminal saccharides. Cholesteatoma is characterzed by the presence of a squamous epithelium invading the middle ear, which is believed to have hyperproliferative properties. The hyperproliferative character of cholesteatoma epithlium was confirmed through hyperproliferation associated cytokeratin expression. The aim of this study was to determine whether the hyperproliferative character of cholesteatoma is associated with high capacity of keratin synthesis of basal cell or associated with hyperproliferative suprabasal cell. Using immunohistochemical technique with anticytokeratin monoclonal antibodies (prolifeating and basal cell markers), we investigated cytokeratin expression of human middle ear cholesteatoma to compare with that of the postauricular skin. We also investigated lectin-binding to N-acetylgalactosamine (Dolichos biflorus agglutinin) of cholesteatoma to verify its differentiating characteristics. These results suggest that hyperkeratinization in cholesteatoma may not be due to hyperproliferation of basal cell compartment, but may rather be caused by proliferative suprabasal compartment. Computed tomographic changes of maxillary sinus after Caldwell-Luc operation. The 1st China-Korea Medical Conference; Beijing, China : Jul 8-10, 1997 For over 100 years, the Caldwell-Luc operation was one of the most frequently performed operations for the management of maxillary sinus diseases. The purpose of this paper is to observe the postoperative changes of maxillary antral walls after Caldwell- Luc operation by computed tomograms of maxillary antra. Computed tomograms of 69 cases of maxillary antra were reviewed. Among them, there were 29 cases of normal control group, 16 cases of chronic sinusitis group and 24 cases of post Caldwell-Luc operation group. The average period after the surgery was 25.3¡¾10.4 years. There were 6 parameters which were thought to represent the dimension of maxillary sinus. In coronal plane, 5 parameters were measured at the mid-portion of the crista galli level. And one parameter (AP diameter) was measured in the axial plane. In postoperative group, there were significant decreases in the parameters of maxillary width, middle meatal communication width and AP diameter in comparison with the normal or chronic sinusitis group. Also in postoperative group, there were significant increase in the distance between inferior turbinate and medial wall of maxillary sinus. The results showed that the bony walls of maxillary antrum after Caldwell-Luc operation were contracted centripetally and quite similar to hypoplastic maxilla. The contributing factors for this change were thought to be loss of bony walls (anterior, middle meatal and inferior meatal), bony wall thickening and radical removal of antral mucosa which later replaced with fibrotic tissues. |
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| 1998 | ||||
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Mechanism of apoptotic cell death in cholesteatoma epithelium. The 21st Midwinter Meeting of Association for Research in Otolaryngology; St. Petersburg , U.S.A.: Feb 15-19, 1998 Accumulation of keratin debris in the middle ear is one of the characteristics of the cholesteatoma. It is related to increased rate of cell death and differentiation of keratinocytes compared to normal skin. This kind of cell death is known as apoptosis. Fas protein is a cell surface protein known to perform critical functions in the events of apoptotic cell death. In this study, we planned to investigate the apoptotic cell death and expression of Fas in both normal and cholesteatoma epithelia. Ten cholesteatomas and retroauricular skins were obtained from patients undergoing middle ear operations. Detection of the fragmented DNA in apoptosis was done by in situ TUNEL methods and agarose gel electrophoresis. For the morphologic confirmation of apoptosis, transmission electron microscopy (TEM) was done. Immunohistochemistry was also performed for detection of Fas expression on the tissues. In TUNEL staining, many positive staining nuclei were observed in entire layer of cholesteatoma epithelium whereas a few positive cells were found on the upper layer of retroauricular skin. Typical ¡°ladder pattern¡± was seen on the gel electrophoresis of the genomic DNA of cholesteatoma. On TEM study, we observed condensation of chromatin in the keratinocytes of the cholesteatoma epithelium. Immunohistochemical studies revealed that Fas protein was expressed in all layers, especially strong in the upper layer of the cholesteatoma epithelium. Retroauricular skin showed weak Fas positive reactions only in the upper layer. Above results shows the increased apoptotic cell death and up-regulated expression of Fas in cholesteatoma epithelium. Since Fas is known as an apoptosis triggering protein, the authors suggest that the accumulation of keratin debris is due to increased apoptotic cell death related to Fas protein. Further investigation about the roles of Fas in the cholesteatoma epithelium would be needed. Expression of lysozyme and lactoferrin in the immortalized rat middle ear and eustachian tube epithelial cells. The 21st Midwinter Meeting Association for Research in Otolaryngology; St. Petersburg , U.S.A.: Feb 15-19, 1998 The secretory lysozyme and lactoferrin have been found in most of the bodily secretions that cover the human mucosal surfaces and immuno-localized various mucosal epithelial and glandular cells. Large amounts of lysozyme and lactoferrin have been detected in the middle ear effusion. Immunohistochemical demonstration of these bactericidal secretory products in the epithelial cells of the tubotympanum have been observed in several species. Even though there are some differences among different species, it is generally believed serous cells of the epithelium as well as submucosal gland in the respiratory tract secrete these bactericidal products. In particular, middle ear epithelial cells have no subepithelial gland, therefore secretory cells of the epithelium might play a role as main sources of bactericidal secretory products. The regulation of synthesis and secretion of these enzymes in the middle ear and eustachian tube, however, is poorly understood. The purpose of this pilot study was to establish an in vitro model in order to investigate molecular mechanism regulating these bactericidal secretory products as well as cellular and molecular mechanisms involved in bacteria-host interaction. We have already established immortalized cells from rat middle ear epithlial and eustachian tube epithelial cells These immortalized cells have been obtained from the transfection of primary culture of middle ear and eustachian tube epithelial cells with Adeno 12-SV 40 hybrid virus. Immunocytochemistry and immunoblotting analysis were used to investigate the expressions of these bactericidal secretory products in theses cell lines. Both analysis reveal the expressions of lysozyme and lactoferrin in middle ear as well as eustachian tube cells. The present results suggest that these cell lines expressed these secretory products in our culture condition. These cell lines will provide a new avenue of research in defining cellular and molecular mechanisms involved in the regulating expression of these bacteriostatic and bactericidal secretory products. A combined therapy of low power laser and Gingko-extract on sudden deafness. The 7th Korea-Japan Joint Meeting of Otorhinolaryngology-Head and Neck Surgery; Seoul : Apr 10-11, 1998 Sudden deafness is a rapidly progressive, partial or complete, typical unilateral sensorineural hearing impairment, which is frequently encountered with no known specific etiology in clinical practice. Many treatment protocols about this disease have introduced until now, but they did not make us satisfied. Recently, a new combined therapy of Laser and Gingko-extract has been introduced, which rationale is reactivation. The purpose of this study is to analyze clinical result of this trial by comparing with that of basic data for application of this therapy as a new treatment modality on sudden deafness. In this study, 51 patients was treated with Laser and Gingko-extract therapy and 37 patients was treated with anticoagulant therapy as control. Both groups were combined with steroid therapy. Treatment with this trial had as a good result as anticoagulant therapy, and it was more comfortable to patients without side reactions. Laser-assisted uvulopalatopharyngoplasty for snoring and obstructive sleep apnea: a long-term follow-up. The 7th Korea-Japan Joint Meeting of Otorhinolaryngology-Head and Neck Surgery; Seoul : Apr 10-11, 1998 LAUP has been introduced in Koreafor 5 years as a new modality of treatment for snoring and obstructive sleep apnea syndrome (OSAS). We tried to evaulate the effects of the LAUP at 3 months and 3 years after the surgery. We analyzed the 67 patients of snoring and OSAS who were treated with LAUP. The results of the surgery were evaluated with interview at 3 years after the surgery. Among them, 27 patients of OSAS underwent polysomnographical studies preoperatively and postoperatively. For the simple snorers, significant improvements were observed in 77.5%(31/40) at 3 months and 67.5% (27/40) at 3 years after the surgery. However among the OSAS patients, 48.1%(13/27) at 3 months and 37%(10/27) showed significant improvement (change in RDI over 50%). In conclusion, LAUP is a good treatment modality for simple snorers. However, we need long-term follow-up for deciding the successful surgical result in patients of OSAS. Congenital cholesteatoma in children with special reference to a cause of acquired cholesteatoma. The 7th International Congress of Pediatirc Otorhinolaryngology; Helsinki , Finland: June 7-10, 1998 The cause of middle ear cholesteatoma has its origins in processes that occur in early infancy. In recent there has been an increasing number of case reports and an apparent increase in interest in congenital middle ear cholesteatoma in children. The actual incidence of congenital cholesteatoma in children is substantially greater than the literature indicates. In this sense, we believe that congenital cholesteatoma in the middle ear can cause acquired cholesteatoma in children. To determine whether congenital cholesteatoma in children may be also a 41 source of acquired cholesteatoma. By analysing findings of myringoscopy, temporal bone computed tomography and operation, we reviewed 10 suspicious congenital cholesteatomas in children including 8 typical congenital cholesteatomas in children. Suspicious cases, when compared with typical cases, had similar cholesteatoma involvement and extension, similar ossicualr destruction patterns, and less suppressive pneumatization of the mastoid air cells. This review supports that these clinical evidences may be possibly a greater source of congenital origin in some children cholesteatomas than we expected. Correlation of ECP and IgA in atopic and non-atopic nasal polyp. The 3rd Asian Research Symposium in Rhinology; Nagoya, Japan : Aug 28-29, 1998 The eosinophils are the most prevalent inflammatory cell type in nasal polyp tissues. They are up-regulated by autocrine and paracrine signals by cytokines such as IL-3, IL-5 and GMCSF. And the polyp environments are related with delayed eosinophil apoptosis. Currently there are evidences suggesting that IgE, IgG and IgA, especially sIgA stimulate eosinophil degranulations in vitro. Also there is a report that the concentration of ECP and IgA are correlated in the nasal and bronchial lavage fluid. This study was designed to compare the levels of ECP with the levels of total IgA and secretory form IgA antibodies in the nasal polyp tissues. We studied polyp tissues of 51 patients with nasal polyposis. They were classified into 2 groups as allergy(N=37) and nonallergy group(N=14). Group I was allergy (N=37) with criteria of skin prick test wheal size > 1mm to Dermatophagoides pteronyssinus and RAST positive. Group II was defined as non-allergy(N=14) excluding allergy by all negative response to 50 common allergens on skin prick test and < 160 IU/ml of serum total IgE. The nasal polyps were taken with nasal cutting forceps under general or local anesthesia. The polyp tissues were immediately frozen and stored at -70¡£ C. The samples were thawed, ground in Elvejhem-Potter homogenizer, centrifuged and stored as fluid state at -70 ¡£ C. ECP concentration was measured by commercial RIA kit. The total IgA and sIgA were measured ELISA. The immunohistochemical staining of the polyp tissues for EG2+ cells were performed by monoclonal antibodies to EG2 cell. The cell counts were performed under light microscopy (¡¿200) and presented as cells/mm2. The statistical significance was tested using non-paired T-test and Spearman¡¯s rank correlation. In the nasal polyp tissues the results can be summarized as follows; ECP levels showed variable values in allergic or nonallergic groups. And ECP level did not correlate with EG2+cell counts. The mean values of total IgA and sIgA were 330.18 ¡¾303.918 and 32.77¡¾45.60(mg/mL) in allergy polyp group and 240.45¡¾275.16 and 27.47¡¾41.22(mg/mL) in non-allergic group. The total IgA and sIgA concentrations were correlated. The correlation between the ECP concentrations and total IgA showed statistical significance(R=0.38, p < 0.05) in atopic group. But the correlation between the polyp ECP concentrations and total IgA in non-atopic group. Also the correlation between the polyp ECP concentrations and did not show statistical significance in both group. In the atopic nasal polyp; 1) The function of IgA could be considered as related with the release of the ECP from the eosinophils in the nasal polyp tissues. 2) The factors for the recruiting the IgA in the nasal polyp tissues should be further evaluated. Epithelial differentiation in the developing murine Eustachian tube and middle ear. The 102nd Annual Meeting of American Academy of Otolaryngology –Head and Neck Surgery; San Antonio , U.S.A.: Sep 13-16, 1998 The mechanism involved in cell differentiation during organogenesis of the eustachian tube and middle ear are not well understood. However, the differentiation of one type of epithelial cell into a specialized cell, such as a ciliated or secretory cell, is believed to be controlled by a genetic message encoded in the cell and by the influence of the mesenchymal cells underlying the epithelium. It is well known that epithelial-mesenchymal interactions are required for epithelial differentiation in organogenesis. A detailed study on the development of the epithelium in the eustachian tube and middle ear will be helpful in understanding how an epithelial differentiation occurs in the developing eustachian tube and middle ear. The present study was undertaken to establish the expression of cytokeratin, laminin and cadherin in developing murine eustachian tube and middle ear using immunohistochemistry. 34 BALB/c mice, ranging in age from gestational day 13 through postriatal day 7, were used for this study. Gestational age was determined by the vaginal plug technique. All specimens of different ages were prepared for immunohistochemical staining(cytokeratin, laminin, cadherin). In this study, laminin A was intensively recognized in the epithelium on gestational day 16 in which the development of ciliated cells was first observed. The expression pattern of cytokeratin, laminin and cadherin seemed to reflect the maturation of the epithelium in the murine developing eustachian tube and middle ear. These findings suggest that epithelial differentiation of developing murine eustachian tube and middle ear is controlled by epithelial-mesenchymal interaction. Immunohistochemical study on proliferative activity of experimental cholesteatoma. The 5th International Academic Conference on Immunobiology in Otology, Rhinology and Laryngology; Siena, Italy : Oct 11-14, 1998 Cholesteatoma is characterized by the presence of a squamous epithelium invading the middle ear, which is believed to have hyperproliferative properties. The hyperproliferative character of human cholesteatoma epithelium was confirmed through various hyperproliferation associated antibody expressions. Several animal models have been introduced to study cholesteatoma pathogenesis. Among them, canal ligation model using Mongolian gerbils is of much interest because it can potentially provide new information on cholesteatoma pathogenesis, especially bone destruction mechanism. In this study, we induced canal ligation cholesteatoma using Mongolian gerbils and investigated the hyperproliferative nature of canal ligation cholesteatoma by using immunohistochemical technique with proliferation markers (cytokeratin 16, PCNA, EGF-R) and PLC-rl. In this result, canal ligation cholesteatoma using Mongolian gerbils showed the hyperproliferative character in the suprabasal cell layer like human cholesteatomas. This result will provide a good morphological basis for future cholesteatoma animal research concerning the pathogenesis of cholesteatoma. Detection of DNA virus in atopic and non-atopic polyps with PCR. The 3rd Asian Pacific Congress of Allergology and Clinical Immunology; Manila , Philippine: Dec 8-12, 1998 The purpose of this study is to provide basic data for the presence of DNA virus in human nasal polyps and to compare the difference of viral detection between atopic and non-atopic nasal polyps. We defined atopic patients as demonstrating a specific IgE RAST positive reaction or >2 positive reaction score on an allergic skin test. We obtained polyp tissues from 10 atopic (seven patients were allergic to D.pteronyssinus and D.farinae) patients from whom viral DNA was isolated and analyzed by PCR and electrophoresis. The number of atopic and non-atopic patients showing viral infection by PCR analysis was low. EB virus was detected in 2 of 10 atopic and 1 of 10 non-atopic nasal polyp patients. Other viruses (including Human Herpes virus type 6, cytomegalo virus, human papiloma virus type 16, 18, 33 and adeno virus) were not detected in any patients. In polyps. However, our results suggest that the EB virus may not be as significant in the formation of nasal polyps as previously reported in China. The role of viral infection should be further studied in RNA viruses such as rhino viruses. Primary parapharyngeal space neuroblastoma. The 1st World Congress on Head and Neck Oncology; Madrid, Spain : Dec 12, 1998 Although neuroblastoma is a relatively common malignancy of childhood, it is rarely of head and neck origin. Fifty-to-eighty percent of neuroblastoma arise from the adrenal medulla and retroperitoneal sympathetic ganglia. While less than 5% of neuroblastoma arise from the cervical sympathetic chain, the head and neck is most affected with metastatic disease. This tumor can not easily be distinguished from the other malignancies that may originate in or metastasis to head and neck. We encountered a case of primary neuroblastoma arising from parapharyngeal space in an infant. The patient, a 7-monthold male, presented with multiple neck masses without any other symptoms. Needle aspiration cytology showed small round cell malignancy. Urine VMA, HVA were elevated. Magnetic resonance imaging showed multiple lymph nodes. Abdominal and chest computed scan showed no abnormal uptake except cervical area. Complete surgical excision was done at the expense of sacrificing the sympathetic nerve trunk. The pathologic metastatic neuroblastoma in 8 out of 17 nodes. No recurrence was noted during follow-up, although rightsided Horner syndrome persisted. Surgical intervention can result in a good prognosis for low stage cervical neuroblastoma; however, long term follow-up is important. |
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| 1999 | ||||
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Expression of muc1, muc2, and muc5ac mRNAs in the immortalized rat middle ear and eustachian epithelial cells. The 22nd Midwinter Meeting of Association for Research in Otolarylgology; St. Petersburg , U.S.A.: Feb 13-18, 1999 Mucus is an integral part of the mucociliary system of the tubotympanum in that it play an important role in the protection of the middle ear from invading pathogenic organisms and in the pathogenesis of otitis media. Several mucin genes that are expressed in upper airway have been cloned in recent 43 years. It has been shown that in human middle ear effusions, there is an expression of Muc5AC (DA Hutton, Glycoconjugate J. 15:285, 1998). In addition, Muc5B mRNA has been shown to be expressed in human middle ear epithelial cells obtained from patients suffering from otitis media (H Kawano, Abstract of 21st ARO). In an effort to establish the normal cellular function and pathogenesis of the otitis media, we have established cell lines from the rat middle ear (SJ Jin et al, Annals Otol, Rhinol and Larygol, in press) and eustachian tube epithelia (SJ Jin, unpublished). As a part of the characterization of these cell lines, we have screened the expression of a battery of mucin genes in these cells using partial cDNAs of three rat mucin genes (rMuc1, rMuc2, and rMuc5AC). These three mucin genes were consistently expressed in both middle ear and eustachian tube epithelial cell lines as well as in the primary cultured epithelial cells. These results suggest that these cell lines will be a useful cell model to study the cell biololgy of the middle ear and tubal epithelial cells as well as to study the molecular pathogenesis of otitis media such as bacteriahost interaction and signaling transduction. Expression of PLC- 1 in experimental cholesteatoma. The 7th International Symposium on Recent Advances in Otitis Media; Ft. Lauderdale , Florida, U.S.A. : Jun 1-5, 1999 Cholesteatoma otitis media is characterized by the presence of a squamous epithelium invading the middle ear. Its pathogenesis including hyperproliferative nature is still unknown. Several laboratory animals have been used to model cholesteatoma formation to provide new information on cellular proliferation. Phospholipase C (PLC)-1 plays a central role in signal transduction and it is important in cellular growth, differentiation and proliferation. The purpose of this study is to elucidate the distribution of PLC-1 in normal meatal skin and cholesteatoma matrix of experimental animals. In this study, we induced canal ligation cholesteatoma using Mongolian gerbils and investigated the expression of PLC-1 in this model by using western blot analysis and immunohistochemistry. On immunohistochemistry, PLC-1 was detected only in basal layer of the deep meatal skin, but was readily detectable in both the basal and suprabasal layers in cholesteatoma matrix. By western blot analysis, considerable higher levels of PLC-1 protein were detectable in experimental cholesteatoma matrix. In conclusion, overexpression of PLC-1 in experimental cholesteatoma matrix suggest a possible derangement of enhanced growth signal transduction in keratinocytes. So this animal cholesteatoma model can be used for the future study of cellular proliferation of cholesteatoma. Signal transduction mechanism involved in bacteria-induced mucin overproduction. The 7th International Symposium on Recent Advances in Otitis Media; Ft. Lauderdale , Florida, U.S.A. : Jun 1-5, 1999 Bacteria-induced mucin overproduction has been known to play an important role in the pathogenesis of upper respiratory infectious diseases including otitis media and chronic bronchitis. In chronic otitis media with effusion, mucin has been shown clearly as an important factor in causing hearing loss. The molecular mechanism underlying H. influenza-induced mucin overproduction are unclear. Here we show that H. influenzae up-regulates mucin MUC2 and MUC5 transcription via activation of MAP kinase pathways. Activation of MUC2 and MUC5 transcription is mediated by unclear factor NF-B. These studies bring new insights into signal transduction mechanism underlying host-bacterial interactions and more specifically into molecular pathogenesis of H. influenzae-caused infectious diseases and may lead to new therapeutic intervention for inhibiting mucus overproduction in both otitis media and chronic bronchitis. Secretory gene expression in the immortalized rat middle ear eustachian tube epithelial cells. The 7th International Symposium on Recent Advances in Otitis Media; Ft. Lauderdale , Florida, U.S.A. : Jun 1-5, 1999 Mucus is an integral part of the mucocilliary system of the tubotympanum, in that it plays an important role in the protection of the middle ear from invading pathogenic organism and in the pathogenesis of otitis media. Several mucin genes that are expressed in the upper airway have been cloned in recent years. In addition, large amounts of lysozyme and lactoferrin have been detected in the middle ear effusion. These secretory mucin and antimicrobial proteins have been known to be regulated depending upon their differentiation or pathogenic conditions. Thus, it is important for the understanding of pathogenesis of otitis media to reveal these regulation mechanisms. Recently, we have established cell lines from the rat middle ear (SJ Jin et al, Annals otol, Rhinol and Laryngol, in press) and eustachian tube epithelia (SJ Jin, unpublished). The goal regulation of these secretory proteins. To achieve this goal, we performed a reverse transcription-polymerase chain reaction (RT-PCR) using MUC1, MUC2, MUC5AC, lysozyme, and lactoferrin probes. All these genes were consistently expressed in both middle ear and eustachian tube epithelial cell lines, as well as in the primary cultured epithelial cells. These results suggest that these cell lines will be a useful cell model to study the cell biology of the middle ear and tubal epithelial cells, as well as to study the molecular pathogenesis of otitis media, such as becterial host interaction and signaling transduction. Expression of aquaporin family of water channel protein in rat tubotympanum in vivo & in vitro. The 7th International Symposium on Recent Advances in Otitis Media; Ft. Lauderdale , Florida, U.S.A. : Jun 1-5, 1999 Proper hydration of airway epithelium in necessary to maintain an adequate oxygen and CO 2 balance, and for the maintenance of appropriate defence mechanisms. The complex fluid movements occurring in the respiratory tract are thought to involve several different aquaporins(AQPs) acting in concert. AQPs are a family of intrinsic membrane proteins that function water selective channels in the plasma membranes of the cells of water transporting tissues. The pathophysiology of several airway diseases such as cystic fibrosis and asthma are also known to involve movements of water into or put of the respiratory tracts. In recent studies, the abnormalities of AQPs would lead to fluid accumulation , mediator release or changes in membrane potential. Here, we investigated the expression of AQPs in rat middle ear and eustachian tube mucosa, immortalized middle ear cell, and eustachian cell by using RT-PCR and immunolabelling to understand the normal distribution of AQPs, which are known 9 different family members. Using RT-PCR with 9 different AQP specific primers, transcripts of all aquaporin families except AQP 2 and AQP 6 were consistently expressed in both middle ear and eustachian tube epithelium. Moreover, these AQP and mRNA were expressed in RMEC-1 and REEC-1, which are rat middle ear and eustachian tube epithelial cell lines, respectively. Interestingly, such a distribution of AQPs showed similar patterns in tracheobronchial systems. Based on these findings, we suggest that AQPs may play important roles in normal physiology and pathophysiology of tubotympanum. MEK 1/2-MAPK pathway is involved in IL-1-induced downregulation of surfactant protein-B(SP-B) transcription in immortalized human middle ear epithelial cell. The 7th International Symposium on Recent Advances in Otitis Media; Ft. Lauderdale , Florida, U.S.A. : Jun 1-5, 1999 Efficient middle ear ventilation and clearance of mucus is dependent on the tubal patency function. Although it has been demonstrated that surfactant like substance in the tubotympanum may act as a surface active agent to lower the amount of pressure required to open the eustachian tube, their role in the pathogenesis of otitis media is unknown. Recently, we have shown that surfactant phospholipids, expressed consistently in the human middle ear epithelial cell line. The aim of this study is how SP-B is regulated by IL-1¡¤, which is one of the most common proinflammatory cytokine, and determine the signal pathway involved. Here we showed that IL-1inhibited SP-B transcription in the human middle ear cell line. These results suggest that the synthesis of surfactant-like substance might be down-regulated in the inflammatory condition such as acute otitis media, and this down-regulation was inhibited by PD98059, a chemical inhibitor selectively blocking the activity of MAP kinase (MEK). Taken together, these results strongly suggest that MEK 1/2-MAPK pathway is involved in IL-1-induced down-regulation of SP-B transcription in human middle ear epithelial cell line. We suggest that the down regulation of SP-B during the early stage of inflammatory process of otitis media aggravate normal tubal patency causing high negative pressure, and MEK blocking agent may be useful to improve tubal patency. Mucin gene expression in the immortalized human middle ear epithelial cells. The 7th International Symposium on Recent Advances in Otitis Media; Ft. Lauderdale , Florida, U.S.A. : Jun 1-5, 1999 The mucus of respiratory tract epithelium including middle ear cleft plays an important role in the normal biology and defense by the mucocilliary system. On the other hand, the overproduction and accumulation of mucus is frequently associated with chronic otitis media with effusion(OME). An increased understanding of the nature of regulation of mucus secretion under controlled culture conditions will shed new light on the normal biology and abnormal regulation in pathologic conditions. Using normal human middle ear epithelial cell line, we investigated expression and regulation of mucin genes. We performed RT-PCR using MUC2, MUC5AC and MUC5B oligoprimers to identify their transcripts in the cell line as compared to those of human middle ear eputhelium results 45 show that MUC2, MUC5AC, and MUC5B genes were consistently expressed, especially in the presence of a high concentration of retinoic acid(10 -7M). Therefore, we suggest that his human middle ear cell line established will provide useful tool for the study of normal biology of the middle ear epithelial cell and in the cell and molecular pathogenesis of the otitis media. Inhibition of bacterial-induced mucin MUC2 and MUC5 transcription by glucocorticoids in epithelial cells. The 7th International Symposium on Recent Advances in Otitis Media; Ft. Lauderdale , Florida, U.S.A. : Jun 1-5, 1999 Bacteria-induced mucin overproduction has been known to play an important role in the pathogenesis of upper respiratory infectious diseases including otitis media and cystic fibrosis. In chronic otitis media with effusion, mucin has been shown clearly as an important factor in causing hearing loss. In cystic fibrosis, 95% of the morbidity and mortality arises from lung disease characterized by chronic lung infection and airway mucin overproduction and obstruction. Although we recently showed that bacteria uoregulates mucin MUC2 transcription via activation of a Src-dependent Ras-MARK-pp90rsk-NF-B pathway, however, little is known about the efficient inhibitors of mucus overproduction and the relevant molecular mechanisms. Because glucocorticoids exert anti-inflammatory activities via inhibiton of nuclear factor NF-B-dependent transcription, we investigated the possibility that glucocorticoids inhibit bacteria-induced mucin MUC2 transcription. Our results indicated that glucocorticoids inhibit bacteria-induced upregulation of mucin MUC2 transcription via a I-B-dependent downregulation of NF-B activity. These studies may lead to new therapeutic intervention for inhibiting mucus overproduction in both otitis media and cystic fibrosis patients. Decision analysis for early diagnosis of small acoustic neuroma. The 3rd International Conference on Acoustic Neuroma and Other CPA Tumors; Rome , Italy: Jun 12-17, 1999 For the past 10 years with the development of imaging techniques such as MRI with gadolinium, small acoustic tumors can be detected before significant symptoms have developed. However, in earlier stage of acoustic tumor, due to the lack of its characteristic symptom, suspicion of acoustic neuroma is not easy and detection rate of traditional audiologic methods such as ABR, pure tone audiogram with speech discrimination score is relatively low contrary to expectation. So need for other method to make the correct diagnosis at an earlier stage raises its head. We reviewed symptomatology, diagnostic approach and management of small acoustic neuromas to make a decision analysis tree their diagnostic work-up. From June 1994 through May 1998, 25 patients with a small acoustic neuroma (less than 1.5cm) were managed at 2 University Hospitals. we analysed these 25 patients through age, sex, chief complaint, size of tumor, preoperative and postoperative audiologic studies, caloric test, treatment modalities and preoperative and postoperative imaging study. Acoustic neuroma had variable symptoms and most common initial symptom of our case was tinnitus (48.8%). One third of cases had unusual intial presentation such as sudden deafness and detection by chance. About half of cases showed near normal hearing and the sensitivity of ABR was relatively lower than we thought. Two out of 5 in observation group showed a abrupt deterioration of hearing. In conclusion, because suspicion of acoustic neuroma in patient with unilateral hearing loss, tinnitus and dizziness is very important, we made the decision analysis tree in diagnosis of small acoustic neuroma which consisted of earlier intervention of MRI based on a costeffective approach. Management of attic cholesteatoma: personal experience. The 22nd Polizer Society Meeting: 2000; Zurich, Switzaerland: Aug 15-19, 1999 The goal of the surgery for cholesteatoma in the middle ear is to provide the patient with a dry, safe ear and good hearing. An additional goal is not only to maintain a normal ear canal contour, that is, avoiding cavity problems, but also to minimize the need for long-term care of the operated ear. These are some attic cholesteatomas in which the middle ear is aerated and free of significant disease. So attic cholesteatoma surgery is thought to be reconstructive rather than destructive and it can be a prophylactic operation. In this study, I attempted to describe prerequisities for atticoplasty for attic cholesteatoma, which is one of the reconstructive surgical procedures for the middle ear. During the last 10 years, I managed surgically about 200 cases of attic cholesteatoma, among which there were 30 cases of atticoplasty, about 30 cases of mastoid obliteration, about 30 cases of intact canal wall mastoidectomy, and about 110 cases of open cavity mastoidectomy. I analysed 30 cases of atticoplasty with special reference to period of postoperative care and hearing results, as compared to cases with mastoid obliteration and open cavity mastoidectomy. I concluded that the prerequisties for atticoplasty during surgery for attic cholesteatoma were as follows; (1) no otorrhea at the time of operation; (2) intact posterior mesotympanum in the operation field; and (3) removal of incus and malleus head during the operarion. Detection of DNA virus with PCR in human nasal polyp. The 103rd Annual Meeting of American Academy of Otolaryngology-Head and Neck Surgery; New Orleans, U.S.A. : Sep 26-30, 1999 The virus has been considered as an etiological agent in the formation of nasal polyp. But controversy still exists. For example, study from Canadahad shown that there was no detectable virus from human nasal polyp with DNA hybridization (EBV, HSV I, Adenovirus). But study from Hong Konghad shown that EBV was detected in 69% of the nasal polyp patients with PCR and in situ hybridization. To compare the difference of viral detection rate between atopic and non-atopic nasal polyps, we performed routine allergy screening test (nasal smear, TEC, TIgE, Dp and Df specific IgE, allergic skin test with 50 allergens). Nasal polyp tissues were obtained and processed for PCR in 20 patients (atopy:10, non-atopy:10). PCR for viral DNA was performed with primers of EBV, HHV 6, CMV, adenovirus and HPV type 16, 18, and 33. EBV was detected in 3 patients(3/20, 15%) including 2 atopic patients (2/10) and 1 non-atopic patient(1/10). No other virus (HHV 6, CMV, adenovirus and HPV type 16, 18, and 33) was detected with PCR. In this study, HHV 6, CMV, Adenovirus and HPV type 16, 18 and 33 could not be considered as an etiological agent for nasal polyp formation. In Korea, total ENV detection rate(15%) in nasal polyp tissues was higher than Canadabut relatively lower than in Hong Kong where EBV infection is prevalent. EBV was detected in both atopic and non-atopic nasal polyp tissue without significant difference. Virus such as EBV can be regarded as an etiological factor for nasal polyp formation in Korea. Careful post-operative follow-up for reccurence of nasal polyps of the EBV positive patients is needed for further study. |
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| 2000 | ||||
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Connexin 26 mutations in Korean non-syndromic hearing loss. The 23th Midwinter Meeting of Association for Reseach in Otolaryngology; St. Petersberg , U.S.A.: Feb 20-24,2000 Mutation in the GJB2 are a major cause of autosomal recessive and sporadic types of congenital deafness. The 35delG is the most frequent type of mutation in Caucasian and European population. However, several other forms were reported, like 167delT among Ashkenazi Jews and R143W in Africans. The present study investigated the mutations of connexin 26 (Cx 26) found in non-synromic hearing loss(NSHL) patients and newborns in Koreans. The sequencing data for a total of 147 unrelated NSHL patients and 100 audiologically screened newborns were included in this prospective study. Genomic DNA samples from all patients and newborns were sequenced in both directions for detection of Cx 26 mutations. Thirteen different types of mutation were found in the patients and newborns. V271 and E114G are the popular types of polymorphic mutations in both groups. 235delC, deletion and frameshift, was detecte in patients(15 in 294 alleles) and newborns (1 in 200 alleles). 35delG was rarely found in both group. In addition to above mutations, several types of mutations S85P, K41R, S72C, V84A, 176-191del and 299-300del were identified. The family study of the 235delC showed a typical autosomal recessive trait of NSHL in their audiologic evaluation. These results suggest that the different types of Cx26 mutations affect autosomal recessive NSHL depending on different ethnic backgrounds. Connexin 26 mutations associated with non-syndromic hearing loss. The 8th Korea-Japan Joint Meeting of Otorhinolaryngology Head and Neck Surgery; Kyoto , Japan: Apr 6-7,2000 OBJECTIVE : Mutations in the GJB2 gene are a major cause of autosomal recessive and sporadic types of congenital deafness. The 35delG mutation is the most frequent type of mutation in white population. However, several other forms were reported, such as 167delT among Ashkenazi Jews and R143W in Africans. The present study investigated the mutations of connexin 26 (Cx 26) found in patients with nonsyndromic hearing loss (NSHL) and newborns in the Korean population. STUDY DESIGN : The sequencing data for 147 unrelated patients with congenital NSHL and 100 audiologically screened newborns were included in this prospective study. METHODS : Genomic DNA samples from all patients and newborns were sequenced in both directions for detection of Cx26 mutations. RESULTS : Thirteen different types of mutations were found in the patients and newborns. V27I and E114G are the popular type of polymorphic 47 mutations in both groups. 235delC-deletion and frameshift was detected in patients (15 in 294 alleles) and newborns (1 in 200 alleles). 35delG was rarely found in both group. In addition to above mutations, several types of mutations -S85P, K41R, S72C, V84A, 176-191del, and 299-300del-were identified. The family study of the 235delC showed a typical autosomal recessive trait of NSHL in their audiological evaluation of hearing threshold. CONCLUSION : The frequency of 235delC allele showed much higher in the patients (5%) than in newborns (0.5%). We rarely found 35delC mutant in both groups. These results suggest that the different types of Cx26 mutations affect autosomal recessive NSHL according to ethnic background. Inner ear anomaly with CSF leakage. The 2nd Video Seminar on Otology and Neuro-otology; Stara Zagora , Bulgaria : May 19-20,2000 Anomaly of the inner ear is associated with varying degrees of hearing impairment. There is also a risk of fistulous communication between the subarachnoid space and the middle ear cavity in some cases that are presented as cerebrospinal fluid otorhinorrhea follwed by recurrent attacks of meningitis. A 13-year-old boy with sensorineural hearing loss of the left ear was presented with watery rhinorrhea. He had two episodes of bacterial meningitis. RN cisternography using Tc-99m- DTPA depicted abnormal radioactivity in the region of the left ear suggesting CSF otorrhea. High resolution CT scans of his temporal bone revealed severe cochlear dysplasia of the left ear. Surgery revealed common cavity anomaly of the left inner ear with CSF leakage into the middle ear through the perilymph fistula which was repaired successfully through translabyrinthine approach. The patient is doing well and has no rhinorrhea or recurrent attacks of meningitis. Hyperproliferation of experimental cholesteatoma. The 2nd Video Seminar on Otology and Neuro-otology; Stara Zagora , Bulgaria : May 19-20,2000 In this study, we induced canal ligation cholesteatoma using Mongolian gerbils and investigated the hyperproliferative nature of canal ligation cholesteatoma by using immunohistochemical technique with proliferation markers (cytokeratin 13/16, PCNA, EGFR, thrombomodulin, PLC-1, PI3K) and western blot analysis (EGFR, PLC-1, PI3K). In this result, canal ligation cholesteatoma showed more intense localization of cytokeratin 13/16, PCNA, EGFR, thrombomodulin, PLC-1 and PI3K proteins than controls on immunohistochemistry. By western blot analysis, considerable higher levels of EGFR, PLC-1 and PI3K protein were detectable in canal ligation cholesteatoma. This result will provide a good morphological basis for future cholesteatoma animal research concerning the pathogenesis of cholesteatoma. Signal transduction pathway in experimental cholesteatoma using Mongolian gerbils. The 6th International Conference on Cholesteatoma and Mastoid Surgery; Cannes , France: Jun 29 - Jul 2,2000 Cholesteatoma is characterized by the presence of a keratinizing epithelium that is believed to have hyperproliferative nature. Several laboratory animals have been used to model cholesteatoma formation to provide new information on cellular proliferation. The proliferation and differentiation of cell in specialized tissues and expression of their properties are under the control of a large number of regulatory processes and complex interactions called signal transduction. Signal transduction pathway may be initiated by external signals such as growth factors, which bind to receptors and activate tyrosine kinases in the plasma membrane. These kinases activate phospholipase C-1 (PLC-1)protein, which in turn stimulates a downstream switch kinases to initiate transcriptional activation of genes in the nuclei of keratinocytes. The purpose of this study is to elucidate the distribution of epidermal growth factor receptor (EGFR), phosphatidylinositol 3 kinase (PI3K), and PLC-1 in deep meatal skin, retroauricular skin and cholesteatoma matrix of experimental animals. In this study, we induced canal ligation cholesteatoma using Mongolian gerbils and investigated the expression of EGFR, PI3K, and PLC-1 in this model by using western blot analysis and immunohistochemistry. By western blot analysis, considerably higher levels of EGFR, PI3K and PLC-1 proteins were detectable in experimental cholesteatoma. On immunohistochemistry, experimental cholesteatoma showed more intense localization of EGFR, PI3K and PLC-1 proteins than deep meatal skins and retroauricualr skins. In conclusion, overexpression of EGFR, PI3K, and PLC- 1 may contribute to abnormal proliferation and differentiation of experimental cholesteatoma in Mongolian gerbils. So this animal model can be used for the future study of cellular proliferation of cholesteatoma. Cholesteatoma: reversible or irreversible. The 6th International Conference on Cholesteatoma and Mastoid Surgery; Cannes , France: Jun 29 - Jul 2,2000 The clinical characteristics, such as invasion, migration, uncoordinated proliferation, altered differentiation, may arise as a result of defective wound healing process, or the induction of preneoplastic transformation or genetic alteration. To date, a number of the 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 may only be overt when cholesteatoma is under specific conditions such as inflammation and infection etc. If these genetic alterations in the development of cholesteatoma may be transient, the pathology of cholesteatoma may be reversible disease. In fact, this reversibility of cholestetoma could be not infrequently experienced in patients with ear canal cholesteatoma. We hypothesize that once cholesteatoma is in normal environment, the cellular or molecular pathology of cholesteatoma may be able to return to normal epidermal characteristics. The aim of this study was to determine whether the hyperproliferation and altered differentiation of cholesteatoma are reversible or not. For this purpose, we used experimental cholesteatoma model induced in gerbils by canal ligation. Although the process of the development of cholesteatoma in this model are different from human middle ear cholesteatoma, the resultant cellular and molecular pathology have been well documented as identical as in the latter. After induction of aural cholesteatoma, ligations were removed and keratin debris was evacuated. Then adequate ventilation was maintained until grossly normal appearance. Using several proliferation and differentiation markers, we examined how different between these treated skin and untreated cholesteatomatous skin. None of our data showed that there were any obvious differences between them. These suggest the altered differentiation and uncoordinated proliferation of induced cholesteatoma may be reversible to be normal. We will here discuss in detail. Functional middle ear surgery for management of retraction pocket & cholesteatoma: short term report. The 6th International Conference on Cholesteatoma and Mastoid Surgery; Cannes , France: Jun 29 - Jul 2,2000 While the incidence of extensive or complicated cholesteatoma has dramatically decreased for the last decades, the early staged or less extensive cholesteatoma and retraction pockets are more frequently found. Especially localized adhesive otitis media, usually in the posterior tympanic membrane, is one of the most difficult dilemmas for the otologist. There are several controversial issues for managing patients with these types of otitis media: 1) conservative care or surgical treatment; 2) which techniques of surgery; 3) whether or not mastoidectomy. We propose a strategy, so-called functional middle ear surgery (FMES) for the management of types of retraction pockets (RP) and early cholesteatoma (CH). FMES was based on safe marsupialization of RP or CH, mucosal preservation, the adequate ventilation, and prevention of RP. In case of attic RP or CH, atticotomy with scutumplasty was made. On the other hand, the procedure to remove posterior annular bone and posterior scutum to allow access tympanic sinus and posterior attic space (designated as posterior sinusectomy with reconstruction were applied to sinus RP or CH.Early tensa cholesteatoma would be managed as the combination of atticotomy and posterior sinusectomy. If the disease seems to extend to mastoid, endoscopes were introduced transmeatally or transcortically. If cholesteatoma extensively occupied in mastoid, complete mastoidectomy was made. However, other inactive pathologic conditions such as effusion, cholesterol granuloma, and granulation etc. would be managed as endoscopic removal or mininal mastoidectomy. Over a period of 4 years, 50 primary procedures based on FMES were performed for these diseases. We will discuss the achievements providing safe dry ear and minimal care to the patients by using this strategy as well as its limitation. Analysis of lymph nodes number according to various modification of neck dissection in head and neck cancer. The 5th International Conference on Head and Neck Cancer; San Francisco , U.S.A. : Jul 29- Aug 2, 2000 BACKGROUND AND PURPOSE : The type of neck dissection performed for head and neck cancers depends on the experience of the surgeon and the status of the neck metastasis. The purpose of this study was to quantify the extent of lymphadenectomy achieved according to the various modification of neck dissection based on microscopic pathologic analysis and to analyze the difference among the types of neck dissection. MATERIALS AND METHOD : Charts and pathologic reports in patients who underwent neck dissection from June 1994 to October 1999 were reviewed. Patients who received selective neck dissection or preoperative radiotherapy to the neck were excluded. The 49 samples were 65 cases and then divided four groups : radical neck dissection (group 1), Type 1 modified radical neck dissection (Type 1 MRND by Medina classification, group 2), Type 2 MRND (group 3), Type 3 MRND (group 4). The number of lymph nodes counted by pathologic microscopic examination for each regions of specimens was recorded. Intergroup difference was analyzed by one-way between-group analysis of variance (ANOVA). RESULTS : The mean number of dissected lymph nodes per specimen was 43.6 in group 1, 38.8 in group 2 and 3, 30.3 in group 4. Group 4 significantly differed from group 1 (p < 0.05). The number of dissected lymph nodes from level II, III, IV of group 4 was significantly different from that of group 1 (p < 0.05). There was no significant difference among the other groups. CONCLUSIONS : The number of dissected lymph nodes decreases as the number of preserved non-lymphatic tissue structures increases and level II, III, IV are less complete regions in functional neck dissection. In functional neck dissection, need more concern for the prevention of possible missed, non-resected lymph nodes. |
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| 2001 | ||||
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Role of downstream signal transduction molecules in experimental cholesteatoma. The 4th Extraordinary Symposium on Recent Advances in Otitis Media; Sendai , Japan: Apr 16-21, 2001 The proliferation and differentiation of cells in specialized tissues and expression of their properties are under control of a large number of regulatory process and complex interactions called signal transduction. Signal transduction pathway may be initiated by external signals such as growth factors, which bind to receptors and activate Src homology 2(SH2)-domain containing signal transduction molecules such as phospholipase C-1(PLC-1) and phosphatidylinositol 3 kinase(PI3K), which in turn stimulates a downstream switch to initiate transcriptional activation of genes in the nuclei of cells. The purpose of this study is to elucidate the distribution of epidermal growth factor receptor(EGFR) and platelet-derived growth receptors-and-(PDGFR-and-) including PLC- 1 and PI3K in deep meatal skin, retroauricular skin and cholesteatoma matrix of experimental animals, and to clarify the role of growth factor receptors and downstream signal transduction molecules in experimental cholesteatomas. In this study, we induced canal ligation cholesteatomas using Mongolian gerbils and investigated the expression of EGFR, PDGFR-and-, PLC-1 and PI3K in this model by using western blot analysis and immunohistochemistry. Higher levels of EGFR, PI3K and PLC-1 were detectable in experimental cholesteatomas. Detectable levels of either PDGFR-or PDGFR-‚ were not expressed by experimental cholesteatoma specimens. In this result, the increased expression of PLC-1 and PI3K by experimental cholesteatomas supports the conjecture that defective regulation of PLC-1 and PI3K functions may play roles in both signal transduction pathway and the invasive potential of this pathology. PLC-1 and PI3K may colocalize in signal transduction system of experimental cholesteatomas. Surgery for cholesteatoma in children with special reference to congenital origin. The 4th Extraordinary Symposium on Recent Advances in Otitis Media; Sendai , Japan: Apr 16-21, 2001 The concept of childhood cholesteatoma with features that are different from those of adult cholesteatoma is open to controversy. It can be seen that cholesteatoma is not as frequent in children as in older people. However, the cause of middle ear cholesteatoma has its origins in processes that occur in early infancy. Cholesteatoma occuring in childhood is usually said to be more aggresive than that seen in adults because cholesteatoma in children is more often associated with larger mastoid air cells, more frequent recurrence, and shorter disease history. I believe that some cholesteatoma in children might be of congenital origin, and that eustachian tube dysfunction and infection followed by eardrum perforation are secondary. Infection can activate the dormant congenital cholesteatoma, which may in time perforate the tympanic membrane and exteriorize; the condition may then be diagnosed as acquired cholesteatoma. There is a need for a broader approach during the surgery in differentiating the pathogenesis of cholesteatoma in children from that of adults. I retrospectively reviewed child patients surgically treated for cholesteatoma which origin was congenital or possibly congenital. I present here how to treat and operate on congenital cholesteatoma with my concept. Human -defensin genes expression in normal and inflamed middle ear epithelium. The 4th Extraordinary Symposium on Recent Advances in Otitis Media; Sendai , Japan: Apr 16-21, 2001 We believe that several secretory products such as lysozyme lactoferrin, and other unknowns might play an important role in protection against pathogen and maintenance of the immunity in tubotympanum. Human -defensin (hBDs) is antimicrobial peptides that may play a role in mucosal defense. To define the role of defensin in middle ear cleft, I analysed the expression and regulation of two human -defensin genes (hBD-1, hBD-2) in human middle ear epithelial tissue and human middle ear epithelial cell line (HEI-HMEEC cell line) by using RTPCR. The normal human middle ear epithelium expressed hBD-1 mRNA but a little hBD-2 mRNA. While hBD-2 mRNA was markedly up-regulated in inflamed middle ear epithelium, the expression of hBD-1 mRNA was slightly elevated in four cases of ten inflamed middle ear mucosa, the others of which were similar with those of control mucosa. On the other hand, the pro-inflammatory cytokines such as TNF-and IL-stimulated the expression of hBD-2 mRNA, but not hBD-1 mRNA in HEI-HMEEC cell line. The present study might be a first report to identify human -defensin genes expression at mucosal surface in human middle ear tissue. Moreover these genes may play an important role in maintenance of middle ear innate imunity. These data suggest that in middle ear hBD-2 expression is induced by inflammation, whereas hBD-1 may serve as a defense in the absence of inflammation. Furthermore, these results provide insights into defining mechanisms of dysfunction of tubotympanum and allow better idea of its treatment and prevention of otitis media. Isolated congenital ossicular anomalies. The 7th Bulgarian National Congress of Otorhinolaryngology with International Participation; Plovdiv , Bulgaria: Oct 18-20, 2001 A nonprogressive and conductive hearing loss in the range of 40 to 60 dB with normal tympanic membrane which has no history of trauma or infection is highly suggestive of a congenital ossicular malformation. Stapes anomaly is the most common among the ossicular anomalies, and they are clinically important because hearing loss can be corrected by appropriate procedure. In this study, I attempted to describe pattern of ossicular anomalies encountered in patients who have a normal eardrum. I also analysed the surgical result with special reference to the pattern of ossicular anomaly. I expected 55 cases of congenital ossicular anomalies which were confirmed through the explotympanotomy for the last 15 years. The preoperative and postoperative audiologic findings, operative fingings and CT findings were analysed. In this results, there were 5 types of ossicular anomalies with 13 anomalous patterns among which stapes footplate fixation was the most common anomaly. In conclusion, there was a great diversity of patterns of ossicular anomalies. Stapes anomaly was the most frequently detected in the ossicular anomalies. Stapes footplate fixation was the most common type which was usually bilateral. Anomalies associated with incus and malleus were usually unilateral. The surgical result of congenital ossicular anomaly was generally good. |
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Activation of a Src-dependent Raf-MEK1/2-ERK signaling pathway is required for IL-1 induced up-regulation of human beta defensin 2 in human middle ear epithelial cells. The 25th Midwinter Meeting of Association for Research in Otolaryngology; St. Petersburg , Florida: Jan 27-31, 2002 Otitis media is the most common cause of hearing impairment and the most frequent bacterial infectious disease in children. The molecular pathogenesis of otitis media, however, is not well understood. 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 greatly contribute to innate immunity. -defensins, unlike -defensins, are produced by epithelial cells and serve as the first line of defense mechanism in urinary and respiratory tracts and skin. It is still unclear whether or not -definsins are expressed in human middle ear mucosa. The molecular mechanisms underlying the cytokineinduced up-regulation of human defensin 2(hBD-2) have yet to be defined. Here we show that hBD-2 is expressed at higher level in the diseased human middle ear mucosa and that IL- ¡¤ up-regulates hBD-2 transcription via activation of a Srcdependent Raf-MEK1/2-ERK signaling pathway. These studies may open up novel therapeutic targets for the treatment of patients with otitis media. Expression of defensin in human middle ear cholesteatoma. 2002 Meeting of Collegium Oto-Rhino-Laryngologicum Amicitae Sacrum; Noordwijk, Netherland: Aug 25-28, 2002 BACKGROUND : Human immune system consists of innate and adaptive immunity. Innate immunity ensures prompt and nonspecific defensive response. Physical barriers (skin, mucosa), macrophages, complement and wide scope of antimicrobial peptides are the major components of innate immune system. In comparison, adaptive immunity acts specificially and potently, ensuring Ab-dependent and cell-mediated cytotoxicity. Defensins are members of a peptide family with broad spectrum of antimicrobial activity. Recent reports suggest that humandefensin(hBD) 1 is an important component of the mucosal innate immune response towards pathogen colonization. Middle ear cholesteatoma is composed of stratified squamous epithelium (matrix) surrounded by well-vascularized granulation tissue (perimatrix). The invagination theory of the genesis of cholesteatoma considers negative pressure and recurrent episodes of inflammation in middle ear cavity as pathogenetical prerequisites for attic retraction pocket, with subsequent attic cholesteatoma development. STUDY DESIGN : This study aimed, using immunohistochemical techniques and RT-PCR, to establish the eventual presence of human -defensins in middle cholesteatoma and paired retroauricular skin samples, obtained during the surgical treatment. It could be hypothesized that defensin 1, 2 & 3 are up-regulated in cholesteatoma in comparison with retroauricular skin. RESULTS : The immunohistochemical study demonstrated stronger hBD-2 positive staining in middle ear cholesteatoma in comparison with retroauricular skin. No significant differences in hBD-1 expression was detected between cholesteatoma and skin samples. RT-PCR established elevated expression of hBD-2 and hBD-3 mRNA in middle ear cholesteatoma. hBD-1 mRNA was constitutively expressed in cholesteatoma and retroauricular specimens. CONCLUSION : Preliminary experimental results gave us ground to conclude that human -defensins could play an important role in the chronic inflammatory state of middle ear cholesteatoma. Study on the three dimensional structure of the human ossicle using micro CT. The 9th Korea-Japan Joint Meeting of Otorhinolaryngology-Head and Neck Surgery; Seoul , Korea: Apr 25, 2002 BACKGROUND AND OBJECTIVES : Conventional studies of the middle ear ossicles give relatively limided 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 the ossicles, including the length, thickness, strength and angle. MATERIALS AND METHOD : The structure of ossicles obtained from 3 cadavers were analyzed through micro CT 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, length and angle of each ossicle were measured. RESULT : The ratio between the handle of malleus (4.413mm) and the long process of incus (3.559mm) was 1.24 : 1, which acts as a lever of middle ear impedance transformer. The volume fraction, indicating relative strength of ossicles, was higher in the portion close to the articular surface. CONCLUSION : Our preliminary data of ossicular structure analysed by micro CT scan will be helpful for elucidation of ossicles¡¯ structure and further development of artificial prosthesis. Differential diagnosis of ear canal mass. The 9th Korea-Japan Joint Meeting of Otorhinolaryngology-Head and Neck Surgery; Seoul , Korea: Apr 25, 2002 INTRODUCTION : Some middle ear pathologies can extend into the external ear canal. These pathologies are required to underline the importance of their inclusion in the differential diagnosis of the ear canal mass. Moreover, taking a biopsy of these pathologies in the outpatient clinic without proper radiological study is sometimes hazardous. PURPOSE : The purpose of this study is to familiarize the otologists with the ear canal masses. MATERIALS AND METHODS : We analyzed middle ear lesions extending to the external ear canal and lesions peculiar to the external ear canal. These lesions were documented by photographing ear canal and operation finding including radiographic materials (temporal bone CT and MRI). RESULTS : In this study, we experienced 10 middle ear lesions extending to the external ear canal (ear polyps, granulation tissues, tuberculosis, leukemia, Langerhan cell histiocytosis, fibrous dysplasia, chondromyxoid fibroma, papillary adenoma, trigeminal schwannoma, squamous cell carcinoma) and 10 lesions peculiar to the external ear canal (ear canal cholesteatoma, traumatic cholesteatoma, iatrogenic cholesteatoma, cholesterol granuloma, osteoma, wart, ear canal bone fracture, foreign body, facial schwannoma, squamous cell carcinoma). CONCLUSION : In conclusion, we experienced that very rare conditions including skull base tumors could be presented as an ear canal mass. |
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| 2003 | ||||
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Comparative analysis of green fluorescent protein-labeled connexin 26 in the wild type and mutations. The 26th Midwinter Meeting of Association for Research in Otolaryngology; Daytona Beach , Florida, U.S.A. : Feb 23-27, 2003 INTRODUCTION : Connexin 26 (Cx26), one of gap junction proteins, is a critical molecule of potassium recycling between perilymph and endolymph of the cochlea. Mutation of Cx26 causes congenital profound sensorineural hearing loss and it is the major mutant gene of non-syndromic hereditary deafness. In our previous study we showed the differences in the subcellular distribution and the function between the wild type and the mutation of Cx26. The purpose of this study is to demonstrate the difference in the trafficking and assembly of green fluorescent protein (GFP)-labeled Cx26 between the wild type and the mutation in the living mammalian cells. MATERIALS : Coding sequences of connexin 26 were cloned from the genomic DNA of normal subjects and connexin 26 mutation-related deaf patients and inserted into GFP expressing vector to express GFP-labeled chimeric connexin 26 (Cx26-GFP). The vector construct was transfected into HeLa cells using cationic lipid. The expression of GFP tagged connexin 26 was traced in the living cells under the fluorescent microscope. RESULTS : Fluorescence microscopy showed that the wild type Cx26-GFP chimeras were expressed and assembled into the cell membrane. In contrast, mutated Cx26-GFP chimeras were expressed, however, localized only in the cytosol. CONCLUSIONS : Our preliminary data shows the different trafficking and assembling patterns between the wild type and the mutated Cx26 in the living cells. This experimental system using GFP can allow us to do further functional analysis of Cx26 and to prepare the basic data for the gene therapy. Significance of intercellular ¡°cross-talking¡± in 3D-in vitro middle ear cholesteatoma model. The 8th International Symposium on Recent Advances in Otitis Media; Ft. Lauderdale , U.S.A.: Jun 3-7, 2003 BACKGROUND : During years, etiopathogenicity of middle ear cholesteatoma raised many controversies and still a unanimous concept doesn¡¯t exist. From histological point of view this pathological tissue is composed of 2 integrated parts-matrix and perimatrix. It our firm belief that the interaction between their cellular components is essential for the major histopathologicalfeatures of cholesteatoma-hyperproliferation and bone destruction. OBJECTIVES : In order to prove our concept, we design and in vitro model using primary keratinocytes and fibroblasts isolated from middle ear cholesteatoma tissue. An alternative model, using HaCaT cell line as a ¡°skin equivalent¡±, has been developed and the grade of homogeneity between cholesteatoma keratinocytes and HaCaT cells was compared in vitro, focusing on the cytokeratin profile. METHODS : Using enzymatic disaggregation protocol we isolated cholesteatoma keratinocytes and fibroblasts from cholesteatoma samples, obtained during surgery. A subconfluent feeder layer from cholesteatoma fibroblasts was prepared using Mitomycin C (Sigma) and cultured on Transwell (Costrar) system. Upon reaching the confluence, cholesteatoma keratinocytes were trypsinised and co-cultured on the feeder layer for 3-5 days and subsequently air-exposed for 14 days. Cholesteatoma keratinocytes and HaCaT cells seeded without a feeder layer have been used as a control. The protein profile of cholesteatma keratinocytes and HaCaT cells was evaluated through SDS-PAGE electrophoresis and Coomassie blue staining. Immunoblot analysis and immunohistochemistry have been advocated to estimate the cytokeratin profiles, using mouse monoclonal antibody K 8.12 (Sigma) against cytokeratin (CK) 13 and 16. RESULTS : Different protein profile and stronger expression of CK 13 and 16 was demonstrated in middle ear cholesteatoma keratinocytes in comparison with HaCaT cells. The cytokeratins were expressed both in basal and suprabasal layers in cholesteatoma matrix. Bigger stratification was observed in 3D-in vitro system when cholesteatoma keratinocytes and HaCaT cells were cultured with fibroblasts in comparison with control group without fibroblasts. CONCLUSION : Using 3D-in vitro model we demonstrated the significance of intercellular interaction between cholesteatoma matrix and perimatrix. The different cytokeratin profile between cholesteatoma keratinocytes and HaCaT cells gives and argument against the simplified definition for middle ear cholesteatoma as a ¡°skin in the wrong place. Matrix metalloproteinase activity in otitis media with effusion. The 8th International Symposium on Recent Advances in Otitis Media; Ft. Lauderdale , U.S.A.: Jun 3-7, 2003 BACKGROUND : Different pathologic conditions such as tympanosclerosis, atelectasis, adhesion, perforation, and attic retraction appeared in the middle ear and tympanic membrane (TM) as a result of natural course of otitis media with effusion (OME). Atrophic changes both in Matrix metalloproteinase (MMPs) are a family of zinc- and calcium- dependent endopeptidases, which dissolve the unmineralized components of extracellular matrix. Previously Jenning et al reported the presence of MMP-2 and 9 and their putative role in maintaining the chronicity of OME. Chronic activation og MMPs could cause degradation of the extracellular matrix substrates of TM (collagen, fibronectin or laminin) and thus could be attributable to development of OME sequelae. OBJECTIVES : The purpose 53 of this study is to compare the activities of MMP-2, 3, 7 and 9 in mucous, serous and hemorrhagic effusion of otitis media. METHODS : Individual samples were separated in three groups mucous, serous and hemorrhagic (from idiopathic hemotympanum), on the basis of clinical experience. Five samples were selected from eachgroup and subsequently processed with Bradford assay to measure the total protein concentration. Metalloproteinase acitivity was assessed by zymography using gelatin and casein gels. The area of enzymatic degradation was quantitated by densitometry. RESULT : The precursor of MMP-2 (72kDa) was expreesed in all effusions. Its active form (66kDa) was expressed strongly in the mucous effusion, weakly in the hemorrhagic one, and absent in theserous one. MMP-3 and 7 were demonstrated only in the mucous effusion. The precursor of MMP-9(92kDa) was established in all effusions. CONCLUSIONS : We hypothesized that increased expression of the active forms of MMPs in mucous effusion involves changes of TM elasticity and development of OME sequelae such as retraction, atelectasis and effusion. 3D micro-CT images for human ossicles. The 3rd Symposium of Middle Ear Mechanics in Research and Otology; Matsuyama , Japan: Jul 9-12, 2003 PURPOSE : Conventional studies of the middle ear ossicles 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 the ossicles, including the length, strength, and the angle. MATERIALS AND METHOD : The structures of ossicles obtained from 3 cadavers were analyzed through micro-CT( Skyscan , 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 CTAnalyzer TM and Ant TM . Based on the results, the strength, length, and angle of each ossicle were measured. RESULTS : The ratio between the handle of malleus (4.413mm) and the long process of incus (3.559mm) was 1.24 : 1, which acts as a lever of middle ear impedance transformer. The volume fraction, indicating relative strengths of ossicles, was higher in the portion close to the articular surface. CONCLUSION : Our preliminary data of ossicular structure analyzed by Micro-CT scan will be helpful for elucidation of ossicles¡¯ structure and further development of artificial prosthesis. 3D micro-CT images for ossicles destructed by middle ear cholesteatoma. 2003 Meeting of Collegium Oto-Rhino-Laryngologicum Amicitiae Sacrum; Helsinki , Finland: Aug 24-27, 2003 BACKGROUND : Conventional studies of 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. STUDY DESIGN : 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 control, normal ossicles obtained from cadaver were used. The structure of obtained ossicles was analyzed through micro-CT (Skyscan, 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 length and strength of each ossicle were measured. RESULTS : The normal ratio between the handle of malleus (4.413mm) and the long process of incus (3.559mm) was 1.24 : 1, which acts as a levr of middle ear impedance transformer. The volume fraction, indicating relative strengths of normal ossicles, was higher in the portion close to the articular 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 normal and pathological structure of ossicles and further development of artificial prosthesis. Cochlear implantation in a clinical case with Behcet disease. The 24th Polizer Society Meeting; Amsterdam, Netherland: Aug 31- Sep 4, 2003 Recurrent iritis and oral/genital ulcers have been described for the first time as a separated pathological entity by the Turkish dermatologist Hulasi 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. Inner ear involvement in Behcet disease was first reported by Alajouanine et al in 1961. The incidence of hearing loss in Behcet disease has been reported as 12% to 80% in several studies. A 37-year-old man diagnosed with Behcet disease was admitted to our department with complaint of the right side profound hearing loss and dizziness. He was treated with steroid therapy without further improvement. After a period of one year, he suffered from complete hearing loss on the left side. Temporal bone CT scan revealed right cochlear ossification. Cochlear implantation was performed in the left cochlea, partially obstructed by fibrosis, and the electrode was fully inserted without resistance. No healing deficiency was encountered in the following postoperative period. The hearing threshold was restored to 30dBHL, while the dynamic range was relatively narrower than others. We propose the routine hearing check in Behcet disease as a diagnostic strategy. According to our experience, we consider that cochlear implantation is not contraindicated in those clinical cases associated with Behcet disease. A clinical significance of AAO-HNS guideline for Meniere¡ disease. The 107th Annual Meeting of American Academy of Otolaryngology-Head and Neck Surgery; Orlando, Florida , U.S.A.: Sep 21-24, 2003 BACKGROUND AND PURPOSE : The guidelines for Meniere disease recommended from the Committee on Hearing and Equilibrium of the American Academyof Otolaryngology- Head and Neck Surgery (AAO-HNS) in 1995 have been used for reporting results of treatments for Meniere disease. However, these guidelines are sometimes not appropriate for management and reporting for some patients clinically considered as Meniere disease. But there are few publications about their efficacy and significance. The objectives of this study is to review and analyze the symptoms, vertiginous episodes, audiometry, vestibular function test and results of treatment of Meniere disease and to evaluate the significance of AAOHNS guidelines. MATERIALS AND METHODS : The patients with Meniere symptom visited the dizziness clinic of Ajou university hospital between 1994 and 2001 wer eincluded in this study. The medical records were reviewed retrospectively. The characteristics of dizziness (duration, frequency, and episodes), pure tone audiometry (PTA), vestibular function test, and treatment results were carefully analyzed according to AAO-HNS guidelines. RESULTS : Of 550 patients with Meniere symptoms, 198 patients were in the criteria of Meniere disease. They were classified to 75 (37.9%) of the definite, 120 (60.6%) of the possible, and only 3 (1.5%) of the probable. In definite group, mean threshold of PTA was 54.3dB and canal paresis (CP) was showed in 33 patients (44%) with mean CP of 53.6%, and peak and descend types of the PTA were dominant (62%). In possible group, mean threshold of PTA was 19.4dB and CP was found in 30 patients (25%) with mean CP of 50.1%. CONCLUSION : Nevertheless, AAO-HNS guidelines for Meniere disease are helpful for communications between doctors, they should be considered to have limitations for diagnosis and treatment in clinical practices. Surgical anatomy of the sphenopalatine artery in lateral nasal wall. The 10th Congress of International Rhinologic Society; Seoul, Korea : Oct 23-26, 2003 OBJECTIVES : We investigated the surgical anatomy of the sphenopalatine artery. First, the location of the sphenopalatine foramen on the lateral nasal wall and the pattern of the main branches of the sphenopalatine artery from the sphenopalatine artery were studied. Second, the course of the posterior lateral nasal artery with respect to the posterior wall of the maxillary sinus, the perpendicular plate of the palatine bone, and the pattern of distribution of its branches on the fontanelle was determined. Third, the distribution pattern on the inferior turbinate was analyzed. STUDY DESIGN : Fifty midsagittal sections of randomly selected Korean adult cadaver heads with intact sphenoid sinus and surrounding structures were used in the study. METHODS : The mucosa on the sphenopalatine foramen and its surrounding mucosa were removed with a microscissors, a fine forceps, and a pick to expose the sphenopalatine artery under an operating microscope (original magnification ¡¿6). RESULTS : The feeding vessels of the superior turbinate were from the septal artery in 36 cases (72%). The feeding vessels to the middle turbinate branch originated from the proximal portion of the posterior lateral nasal artery just after exiting the sphenopalatine foramen in 44 cases (88%). Some portion of the posterior lateral nasal artery ran anterior to the posterior wall of the maxillary sinus in 38%. The major feeding arteries to the fontanelle were from the inferior turbinate branch in 25 cases (50%). In most cases, the inferior turbinate branch was the 55 end artery of the posterior lateral nasal artery (98%). CONCLUSION : The study provides detailed information concerning the sphenopalatine artery, which we hope will help explain the arterial bleeding that may occur during ethmoidectomy, middle meatal antrostomy, conchotomy, and endoscopic ligation of the sphenopalatine artery. Cochlear implantation in a case with Waardenburg syndrome. The 4th Asia Pacific Symposium on Cochlear Implantation; Taipei , Taiwan: Dec 2-6, 2003 Waardenburg syndrome (WS), an autosomal dominant syndromic deafness, is characterized by pigmentary abnormalities and deafness with/without dystopia canthorum (lateral displacement of inner canthi of eye). The prevalence of this syndrome is 1/42000 of the population and 1.43 % of the congenital deafness. This syndrome is both clinically and genetically heterogeneous and is clinically classified into four types, WS types 1-4 according to the accompanying signs such as dystopia canthorum, limb deformity and Hirschsprung disease. Of the four clinical subtypes of WS, the most common are WS1 and WS2. The genetic basis of WS2 is unknown, but 15% of WS2 cases are caused by mutation in MITF (microphthalmia-associated transcription factor). We here present a Korean family of Waardenburg syndrome type 2, which is not associated with MITF mutations. Three affected patients of four family members demonstrate various pigmentary lesions of iris and deafness. Temporal bone CT scan showed the modiolar defect and the hypoplasia of lateral semicircular canals. Severe CSF gush out was noted during the cochlear implantation, however, it was controlled by soft tissue packing around the cochleostomy site, head elevation and mannitol infusion. The patient was discharged without complications and the hearing threshold was restored to 30 dB HL after mapping. |
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| 2004 | ||||
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Expression of gap junction protein connexin 43 and connexin 26 in human choelsteatoma. The 27th Midwinter Meeting of Association for Research in Otolaryngology; Daytona Beach , Florida, U.S.A. : Feb 21-26, 2004 BACKGROUND AND OBJECTIVES : Cholesteatoma is an otologic disease having characteristics of hyperproliferation and differentiation of epithelial cells, and needs intercellular signal exchange through gap junctions as well as intracellular signal pathway. Connexin (Cx) is a gap junction protein for intercellular communication, and especially Cx 26 and Cx 43 are plenty in human epithelial cells. The objective of this study was to analyze the expression and possible roles of Cx 43 and Cx 26 in human cholesteatomas comparing normal epitheliums. MATERIALS AND METHODS : Ten retroauricular skins (RAS), external auditory canal skins (EACS), and cholesteatomas were taken during middle ear operations in Department of Otolaryngology, Ajou University Hospital for this study. Immunohistochemical staining and reverse transcription- polymerase chain reaction(RT-PCR) were used for detection of Cx 43 and Cx 26. The expression patterns of Cx 43 and Cx 26 were also compared with that of a proliferation marker Ki67 for identification of the roles of Cx in cholesteatomas. RESULTS : In human cholesteatomas, Cx 43 were expressed in whole suprabasal layers, especially in middle portion, except basal layer, and Cx 26 were usually expressed supra- and basal layers. But normal RAS showed weak expression of Cx 43 in upper spinosal and granular layers, but not in basal layers, and the restricted localization of Cx 26 in basal layer. The expression of Cx 43 and Cx 26 in EACS was weak but similar patterns to that of cholesteatomas. In RT-PCR, the expression of Cx 43 and Cx 26 were increased in cholesteatomas than in RASs. And Cx 43, and Cx 26-expressed epithelial cells in cholesteatomas were not identical to the Ki-67 expressed cells, suggesting Cx 43 and 26 may be related to differentiation rather than to proliferation. CONCLUSION : Human cholesteatomas showed upregulated expression and different localization of Cx 43 and Cx 26, gap junction proteins for intercellular communication, compared with normal RASs, suggesting that perturbations of intercellular communication through gap junctions may be associated with the pathology of human cholesteatomas. Congenital middle ear cholesteatoma: our experience in 50 cases. The 10th Japan-Korea Joint Meeting of Otorhinolaryngology-Head and Neck Surgery; Tokyo , Japan: Apr 1-3, 2004 INTRODUCTION : There is an increasing awareness of congenital cholesteatomas in recent decades. The location of the congenital cholesteatoma, when possible initially, can be classified in relation to the four quadrant of the eardrum. Gross-pathologically, there are two types of congenital cholesteatoma: a closed keratotic cyst and an open matrix. Patients with opentype congenital cholesteatoma may have a different clinical presentation from the classical description of congenital cholesteatoma. This study aimed to analyze clinical characteristics of each pathologic type of congenital cholesteatoma and to facilitate better understanding of its pathogenesis. MATERIALS AND METHOD : We reviewed retrospectively 45 patients who were diagnosed as congenital middle ear cholesteatoma under its definite criteria in Ajou University Hospitalfor the last 10 years (1994-2003). This study was done by analyzing the patient history, drum finding, temporal bone CT finding, operative finding and pathologic finding. RESULTS : The opentype congenital cholesteatoma which usually originated from posterosuperior quadrant of the mesotympanum showed higher degree of hearing loss and more frequent unusual presentation, and detected at an older age than the closed-type congenital cholesteatoma. CONCLUSIONS : The pathogenesis of congenital cholesteatoma may be different according to its location and pathologic type. The diversity of clinical presentation of congenital cholesteatoma requires further study on its pathogenesis. Activity of matrix metalloproteinase and its tissue inhibitor in effusion of otitis media. The 10th Japan-Korea Joint Meeting of Otorhinolaryngology-Head and Neck Surgery; Tokyo , Japan: Apr 1-3, 2004 Matrix metalloproteinases (MMPs), zinc- and calcium-dependent endopeptidases, dissolve the unmineralized extracellular matrix. They are inhibited by tissue inhibitor of metalloproteinase (TIMP), and the relationship of the levels of activated MMP and TIMP determines the balance between degradation and formation of matrix. Chronic activation of MMPs could cause degradation of the extracellular matrix substrates of tympanic membrane (collagen, fibronectin or laminin) and thus could be attributable to development of OME sequelae. We aim to compare the activities of MMP-2, 3, 7, 9 and TIMP in mucous, serous and hemorrhagic effusions of otitis media. Individual samples were separated into three groups - mucous, serous and hemorrhagic (from idiopathic hemotympanum) on the basis of clinical experience. Five samples were selected from each group and the total protein concentration was measured with Bradfordassay. Metalloproteinase activity was assessed by zymography using gelatin and casein gels. The area of enzymatic degradation was quantitated by denstinometry. TIMP-2 level was measured by ELISA. The precursor of MMP-2 (72 kDa) was expressed in all effusions. Its active form (66 kDa) was expressed strongly in the mucous effusion, weakly in the hemorrhagic one, and absent in the serous one. MMP-3 and 7 were demonstrated only in the mucous effusion. The precursor of MMP-9 (92 kDa) was established in all effusions, while the active form (84 kDa) was detected in both mucous and hemorrhagic effusions. TIMP-2 was expressed only in the serous effusion. We hypothesized that increased expression of the active forms of MMPs and relatively low level of TIMP involves changes of TM elasticity and development of OME sequelae such as atelectasis and adhesion. Isolated congenital stapes anomaly. International Symposium of the Politzer Society on Otosclerosis and Stapes Surgery; Saas-Fee , Switzerland: Apr 22-25, 2004 A non-progressive and conductive hearing loss with normal eardrum, which has no history of trauma and infection, is highly suggestive of a congenital ossicular malformation. Among osscular anomalies, stapes anomaly is the most common, and it is clinically important because hearing loss can be corrected by appropriate procedures. The purpose of this study is to describe patterns of stapes anomaly and to analyse its surgical result with special reference to the patterns of stapes anomaly. I experienced 33 cases (38 ears) of congenital stapes anomalies which were confirmed through the explotympanotomy at Ajou University Hospitalfor the last 10 years. In this studiy, there were 11 anomalous patterns of the stapes among which footplate fixation was the most common anomaly. I could get hearing improvement in 68.4% of my cases after stapes surgery. In conclusion, footplate fixation was usually bilateral, while anomalies associated with incus anomaly were unilateral. The success of the surgical treatment of stapes anomaly might depend on developmental status of the oval window. Unusual presentation of mesotympanic congenital cholesteatoma. The 7th International Conference on Cholesteatoma and Mastoid Surgery; Hague, The Netherland: Jun 22-25, 2004 BACKGROUND AND OBJECTIVE : Many otologists have speculated on the pathogenesis of mesotympanic congenital cholesteatoma which includes epidermoid formation, ingrowth of meatal epidermis, metaplasia, and reflux of amniotic fluid. Recently, tympmic membrane origin theory was proposed as a new pathogenesis of mesotympanic congenital cholesteatoma (Tos; 2000). The location of mesotympanic congenital cholesteatoma, when possible initially, can be classified in relation to the four quadrant of the eardrum. This location, especially anterosuperior and posterosuperior quadrant, is said to be related to its pathogenesis. Some patients with congenital cholesteatoma may have a different location and presentation from the classical description of congenital cholesteatoma. This study aimed to 57 describe unusual presentation of mesotymypanic congenital cholesteatoma with special reference to its pathogenesis. MATERIALS AND METHODS : We reviewed retrospectively 50 patients who were diagnosed as congenital middle ear cholesteatoma under its definite criteria in Ajou University Hospital for the last 10 years (1994-2003), among which 30 patients had lesions confined to the mesotympanum, In this syudy, 30 patients with mesotympanic congenital cholesteatoma were included by analyzing patient history, drum finding, temporal bone CT findings, and operative findings. RESULTS : 15 of 30 cholesteatomas were confined to the posterosuperior mesotympanum, 11 to the anterosuperior, 1 to the anteroinferior, 1 to the posteroinferior, and 1 undetermined origin. Interestingly, there was a case which had two masses both in anterosuperior and anteroinferior portion. 7 cases had no mass shadow on the eardrum which were all originated from the posterosuperior portion of the mesotympanum. The posterosuperior mesotympanic cholesteatoma showed relatively larger size and older age when diagnosed, higher degree of hearing loss, and more frequent unusual presentation than the anterosuperior origin. CONCLUSIONS : The unusual presentation of congental cholesteatoma could not be explained by previously proposed mechanisms. This review suggests that the unusual presentation of mesotympanic cholesteatoma may have a possibility of tympanic membrane origin. Expression of female sex hormone receptors in middle ear cholesteatoma. The 7th International Conference on Cholesteatoma and Mastoid Surgery; Hague, The Netherland: Jun 22-25, 2004 OBJECTIVE : To establish the eventual presence of progesterone receptor (PGR) and estrogen receptor (EGR) in middle ear cholesteatoma (MECh) tissue and to compare their expression between male and female patients. MATERIAL AND METHODS : Immunohistochemical technique was employed for detection of PGR- and EGR-specific immunoreactivity in MECh samples using formalin-fixed paraffin-embedded tissue sections. The positive results were verified with reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS : The morphological study revealed stable expression of progesterone receptor in suprabasal layers of all cholesteatoma samples. Weaker immunoreactivity for PGR was demonstrated in external auditory canal skin (EACS) samples in comparison with MECh, while in retroauricular skin (RAS) samples PGR-specific staining was not discovered. EGR was detected only at mRNA levels. Stronger expression of EGR PCR-products was disclosed in female cholesteatoma samples, while PGR mRNA was predominantly detected in male cholesteatoma specimens. CONCLUSIONS : Our preliminary experimental results give us ground to assume that female sex hormones may play an important role in the regulation of proliferation of middle ear cholesteatoma keratinocytes. Audio-vestibular involvement in patients with Behcet syndrome. The 23rd International Congress of the Barany Society; Paris, France : Jul 7-9, 2004 BACKGROUND : Behcet syndrome, originally described by Dr. Hulusi Behcet in 1937, is a chronic systemic relapsing disorder of young adults with a generalized vasculitis of small vessels with unknown etiology. It has been demonstrated that central nervous system, cardiovascular system, pulmonary and gastrointestinal tract involvement are present. However, there are few articles about ear and vestibular involovement in Behcet syndrome. OBJECTIVES : The present study prospectively investigated the results of the audiologic test and the vestibular function test in patients with Behcet syndrome and analyzed their characteristics. METHODS : Twenty consecutive patients with Behcet syndrome (7 male and 13 female) who were diagnosed and followed by the Department of Dermatology (Behcet clinic) were included in this study. The mean age of the group was 38.9 (21-54) years. The patients were divided into three groups according to the number of criteria (involved site), complete, incomplete, and suspected type. Three of patients were in complete type, nine were in incomplete type, and eight were in suspected type. All the patients were performed the pure tone audiometry and vestibular function test. The patients groups were compared with 20 age- and sex matched healthy controls. RESULTS : The patients complainted auditory symptoms (hard of hearing, tinnitus, and aural fullness) in three (15%), a dizziness in eleven (55%) of 20 patients. Sensorineural hearing loss was present in three patients (15%), one of the were treated with cochlear implantation due to bilateral sudden deaf. Spontaneous nystagmus were detected in two patients (10.0%). And abnormal findings were noted in one (5%) in saccadic movement, five (25%) for bithermic caloric test, and nine (45%) in rotation chair test. Totally, audiologic and/or vestibular involvement were noted in fourteen (70%) of patients with Behcet syndrome, including all three in complete type and eight of nine in incomplete type, and three of eight in suspected type. However, audio-vestibular abnormalities were not noted in age and sex matched healthy controls. CONCLUSION: Audio-vestibular involvement is not infrequent in Behcet syndrome compared with healthy controls. We consider that the audio-vestibular assessment and management may be helpful for the diagnostic evaluation and consultation for the patients with Behcet syndrome. Reversibility of experimental cholesteatoma epithelium using Mongolian gerbils. 2004 Meeting of Collegium Oto-Rhino-Laryngologycum Amicitiae Sacrum: Salvador , Brazil; Aug 22-25, 2004 BACKGROUND : 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 are 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 experimental cholesteatoma induced in gerbils. STUDY DESIGN : 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, CK13/16). 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. Clinical analysis of orbital complications of acute sinusitis according to the age. The 108th Annual Meeting of American Academy of Otolaryngology-Head and Neck Surgery: Newyork , U.S.A.: Sep 19-22, 2004 OBJECTIVES : The purpose of this study is to analyze the common types of orbital complication in children and adults and to compare the symptoms, prognosis and treatment of children with those of adults. METHODS : Retrospective review of patients treated for orbital complications from sinusitis at the Department of Otolaryngology, Ajou University Hospital, Suwon, Korea between March 1998 and July 2003 yield 34 patients. Symptoms, duration of treatment, treatment modality, prognosis and CT finding were analysed. RESULTS : Children less than 17 years old were 24 and 7 years old were 10. Preseptal cellulites were 8 (33.3%) in children and 16 (60%) in adults. Subperiosteal abscess were 10 (41.7%) in children and 2 (20%) in adults. Orbital cellulites were 6 (25%) in children and 2 (20%) in adults. Lid swelling, diplopia and limit of motion were observed 24/24 (100%), 4/24 (16.6%), in children and 10/10 (100%), 2/10 (20%) in adults. Medical treatment was done only 17/22 (70.8%) in children, 6/10 (60%) in adults. Surgical treatment was done 7/24 (29.2%) in children and 4/10 (40%) in adults. Postseptal cellulitis type of orbital complications are much more in children than adults. Orbital complications of children can be more conservatively treated than adults. CONCLUSION : Orbital complications of children are more severe than those of adults. |
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| 2005 | ||||
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Meniere's disease in children The 5th International Symposium on Meniere's Disease and Inner Ear Homeostasis Disorder (California, U.S.A. : Apr 2-5, 2005) Objective: It is a common opinion that typical Meniere's disease seldom occurs during childhood. Meniere's disease in children comprises only a small percentage of all patients with Meniere's disease. The progression pattern of Meniere's disease in children is not known well. The purpose of this study is to analyze the incidence and the characteristic progression of Meniere's disease in children. Study design: Retrospectively study. The patients were diagnosed from Jan, 1995 to Apr, 2003 according to the guideline from AAO-HNS Committee on Hearing and Equilibrium in 1995. Results: The incidence of children with Meniere's disease compared with total number of patients with Meniere's disease for 9 years is 2.6% (3/114), and the incidence of Meniere's disease in children with vertigo is 2.0% (3/147). The three cases of children with Meniere's disease are two 14 and 13-year-old boys and a 10-year-old girl. Two of three cases initially complained of only recurrent bouts of vertigo without any tinnitus, ear fullness, and hearing impairment. And, the early pure tone audiograms showed only high tone loss regardless of complaining hearing loss in all three cases. Thispattern of audiograms was different from usual initial audiograms in adult with Meniere's disease. The decrease of the hearing threshold was observed 1-8 years after the dizziness attacks started. They were usually decreased to a level of mild or moderate hearing impairment. After diuretic treatment, vertigo was generally well controlled, and some cases showed improvement in hearing. Conclusions: Meniere's disease in children rarely develops and may have characteristics of high tone loss in initial audiograms . Management of otitis media with effusion associated with congenital middle ear cholesteatoma The 5th Extraordinary International Symposium on Recent Advances in Otitis Media (Amsterdam, The Netherland: Apr 24-27,2005) Background and objective: Otitis media with effusion (OM E) is sometimes concomitant with congenital cholesteatoma of the middle ear in children. In such cases, the diagnosis might not be made until myringotomy for insertion of a ventilation tube or perhaps not until some time later. Some authors described that congenital cholesteatoma in the middle ear might extend toward and occlude the Eustachian tube orifice, secondarily resulting in acute otitis media or OME. In management of congenital cholesteatoma in children with concomitant middle ear effusion, tympanostomy tube placement prior to or together with definitive cholesteatoma surgery remains a challenging process. This study aimed to analyse clinical characteristics of congenital cholesteatoma associated with OME with special reference to its pathogenic mechanism and management. Methods : I reviewed retrospectively 56 cases who were diagnosed as mesotympanic congenital cholesteatoma under its definitive criteria for the last 10years. Among them, 14case (25%) were associated with middle ear effusion. Results: In this study, 5 out of 14 case with concomitant middle ear effusion were confined to the anterosuperior mesotympanum, 8 to the posterosuperior, 1 undetermined origin. All case were managed with tympanostomy tube placement with or without adenoidectomy together with definitive cholesteatoma removal. Only one case showed recurrent disease. Conclusions: OME can be coincidently associated with congenital cholesteatoma of the middle ear in children because the cumulative· incidence of acute otitis media up to age of 5 years is about 80%. Middle ear ventilation with or without adenoidectomy together with definitive cholesteatoma surgery is necessary in management of congenital cholesteatoma in children with concomitant OME. Do we need antibiotics and antihistamines for treatment of otitis media witheffusion in tertiary care hopital? The 5th Extraordinary International Symposium on Recent Advances in Otitis Media (Amsterdam, The Netherland: Apr 24-27,2005) Background and Objectives: Recently new evidence-based recommendations were introduced for diagnosing and managing otitis media with effusion(OME) in children. However, there are some difficulties to follow the general guidelines in tertiary hospital, because the referred children had previously medications and also showed several symptoms such as allergy and sinusitis. The purpose of this prospective study is to evaluate the efficiency of antibiotics or antihistamines for treatment of children with OME in tertiary hospital. Materials and Methods: One hundred twenty two children with OME diagnosed by pneumatic otoscopy, tympanograms, pure tone audiograms in tertiary Ajou University Hospital, Suwon, Korea, were randomized to receive 6 different medications for 2weeks. We randomly prescribed antibiotic(amoxicillin-clavulanate syrup) in Group l(n=19), antibiotic and steroid(prednisolone) in Group II(n=24), antibiotic and antihistamine(ebastine) in Group lI(n=22), antibiotic, steroid, antihistamine in Group IV(n=21), antibiotic, steroid, mucolytic(Prospan syrup) in group V(n=11), and mucolytic in Group VI(n=24) for control. The children were regularly followed-up every 2 weeks and the decision for cure, observation, or operation was based on usual recommendations. Results: Forty(32.8%) of 122 children were controlled in average 6.9weeks after treatment, and 39(32.0%) were treated with operation(ventilation tube insertion). Fourteen(11.5%) were continuouslyobserved and 29(23.8%) were not followed-up. There was no difference of cure rate of OME among the different six protocols(p>0.05). There was no difference of cure rate among groups used antihistamine(Group III, IV), steroid(Group II, V), and other drugs(Group I, VI) in each to manage the 59 children showing allergic symptoms or positive response in allergic skin tests(p=0.385). Conclusions: In tertiary care hospital, the cure rate of children with OME was not as high as the well-known information, and antibiotics or anti-allergic medications were not more effective than controlfor management of OME. Effect of HGF in invasion of hypopharyngeal squamous cell carcinoma cell line The 10th International Congress on Oral Cancer (Crete, Greece: May 7-11,2005) Background and Objectives: Hepatocyte growth factor (HGF) has known to stimulate proliferation scattering, migration and invasion of various cancer cells. Induction of the matrix metalloproteinase (MMP)-2, 9 and urokinase type plasminogen activator (u-PA) by HGF plays an important role in tumor cell invasion. We examined the effect of HGF/c-Met on matrix metalloproteinase (MMP)-2, 9 and urokinase type plasminogen activator (u-PA) in FaDu cell, a hypopharyngeal squamous cell cancer(SCC) cell line. Materials and Method: We performed RTPCR and Western blot in FaDu cell. Tumor cell invasiveness was assessed by the membrane invasion assay. To examine the role of the MMP-2, 9 and the relation between HGF and MMP in invasion of FaDu cell, RT-PCR and zymography were performed in FaDu cells. And we tested to comfirm the HGF-mediated plasmin activation. Results: 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 FaDuceli and exogenous HGF slightly enhanced the induction of MMP activity in zymogram analysis. The activity of u-PA was detected in FaDu cell and HGF enhanced the activity of u-PA(p < 0.05). Conclusions: These results suggest that HGF may play an important role ininvasion of hypopharyngeal cancer through the activation of u-PA and MMP . Effects of otitis media with effusion on the vestibular system in children XVIII International Federation of Oto-rhino-Iaryngological Societies World Congress (Rome, Italy: Jun 25-30, 2005) Idea: Otitis media with effusion (OME) is one of the most common diseases in children and may be frequently related with dizziness. However, the as~ociation between OME and dizziness seems to be not clear and remains controversy. The purpose of this study is to determine the incidence of dizziness in children with OME, and to investigate whether there is any difference in vestibular function tests between children with OME and control group Method: Twenty six children who had long-lasting (over than 6 months in history) OME, and 21 normal hearing children without OME scheduled for adenotonsillectomy, were given questionnaires and vestibular function tests (VFT) including electronystagmography (ENG) and rotation chair test (RCT). Results: Dizziness was found in 6(23.1 %) of 26 children with OME and 1 (4.8%) of 21 controls (p>0.01). The difference of abnormal findings in VFT between OME group and control was not significant except visuo-vestibular ocular reflex in RCT. Most of the correlations, bilateral vs. unilateral OME, OME with dizziness vs. OME without dizziness, and preoperative vs. postoperative, were not significant. Conclusions: We did not find any evidence of subjective or significantly objective vestibular involvement in children with OME. Long-standing OME (or middle ear effusion) in children may not affect the vestibular function. Conductive deafness with normal eardrum: absence of long process of the Incus 25th Politzer Society Meeting(Seoul, Korea: Oct 5-9, 2005) Objectives: A non-progressive and conductive hearing loss with normal eardrum which has no history of trauma and infection, is highly suggestive of a congenital ossicular malformation. Among ossicular anomalies, absence of long process of the incus have been sometimes suggested. However, there is a suggestion that this kind of pathology may be due to acute otitis media to which the patients succumbed in their infancy or childhood. This conductive hearing loss with normal eardrum is due to resorption of long process of the incus by its potential inflammation. The purpose of this study is to clarify whether the absence of long process of the incus is caused by inflammation or congenital anomaly. Materials and Methods: We experienced 7 cases (4 bilateral cases, 3 unilateral cases) of absence of long process of the incus which were confirmed through explotympanotomy at Ajou University Hospital for the last 10 years. Temporal bone CT, operative and histopathologic findings were analyzed. We also demonstrated 3D reconstructive image and volume fraction of pathologic incuses through 3D micro-CT. Result: 2 bilateral cases showed fibrous changes of long process of the incus instead of its complete absence. All unilateral cases showed resoprtive evidence by inflammation on light micrograph and volume fraction of 3D mjcro-CT of the incus. In temporal bone CT, 1 out of 3 unilateral cases showed relatively decreased pneumatization of the temporal bone of the diseased side in comparison with that of the healthy side. Conclusions: The most likely causes of the lesion of long process of the incus had a possibility of a potential inflammation. However, we could not completely exclude a possibility of congenital anomaly of this lesion. A new method to determine the site of horizontal canal benign paroxysmal positional vertigo; Bowing and Leaning nystagmus 25th Politzer Society Meeting(Seoul, Korea: Oct 5-9, 2005) Objectives : Horizontal canal benign paroxysmal positional vertigo (HC-BPPV) accounts for about 10-20% of all patients presenting with BPPV. The cure rate of HC-BPPV by otolith repositioning maneuver is about 60-90% less than those of posterior canal BPPV. One of causes of this low rate is the difficulty of determining the exact causing site for HC-BPPV using Ewald's second law. The purpose of this study is to develop the new method which can easily determine the causing site of HC-BPPV and evaluate its efficiency. Methods: Seventeen patients with HCBPPV diagnosed in the Dizziness Clinic in Ajou University Hospital, Suwon, Korea, from September, 2004 to July, 2005, were included in this study. The classical method for determining the site is based on comparing the intensity of positioning nystagmus or symptoms in the head positioning test (Ewald second law). The following is the new method. First, we confirm whether the type of HC-BPPV is canalolithiasis or cupulolithiasis on supine position. Then we check the direction of nystagmus when the patient bows the head over 90° (bowing nystagmus) and leans the head backward over 45° (leaning nystagmus) on Sitting position. For canalolithiasis, the causing site is determined as the same direction as that of bowing nystagmus and the opposite direction to that of leaning nystagmus. For cupulolithiasis, the causing site is determined as the opposite direction to that of nystagmus and same direction as that of leaning nystagmus. In the patients showed different causing site between in the Ewald's second law and in new method, we compared the efficiency of two methods using Barbecue maneuver (BM). Results: In 17 patents, there were 9 cases of cupulolithiasis and 8 cases of canalolithiasis. The patients showed the different causing site between two methods were 9 cases including 6 cases of canaloithiasis and 3 cases of cupulolithiasis. Three of these 9 patients were not completely treated by BM based on the causing site following the Ewald's second law, and then cured by just one trial of BM (oppositedirection) based on new method. The rest 6 cases were easily treated by BM based on the direction following new method, but not the classical method (Ewald's second law). Conclusions: The bowing and leaning nystagmus (called by 'Choung's method') is a new method which can easily determine the causing site of HC-BPPV . The relationship between anatomic variations of paranasal sinuses in children and chronic sinusitis The 11 th Congress of the International Rhinologic Society (Sydney, Austrailia : Oct 25-29, 2005) Background: Nowadays, the number of endoscopic sinus surgery taken place in children has increased. Therefore, we need to know the precise anatomy and anatomic variations of the nose, and we also need to know the relationship between the anatomic variations and sinusitis. Method : To assess the extent and distribution of disease as well as associated anatomic abnormalities in this pediatric population, 94 OMU CT scans of children with continued symptoms of sinusitis after failure of extensive medical therapy were reviewed retrospectively. Results : Maxillary sinusitis was the most common sinus infection, followed by ethmoidal, sphenoidal and frontal sinusitis in that order. The agger nasi cell was the most common anatomic variation, followed by the septal deviation, the Haller's cell, the concha bullosa, the paradoxical middle turbinate and the Onodi's cell. There was no significant relationship between the sinusitis and anatomic variations. Conclusion: Anatomic variations in the nose are common in children. Due to the absence of a definitive relationship between the anatomic variations and sinus disease, local, systemic or environmental factors appear to be more important in pediatric sinusitis than the anatomic variations. Clinical manifestations of extranodal NKJT Cell lymphoma. nasal type The 11 th Congress of the International Rhinologic Society (Sydney, Austrailia : Oct 25-29, 2005) Introduction: Extranodal NKfT cell lymphoma, nasal type formerly known as lymphomatoid granulomatosis, polymorphic reticulosis, midline malignant reticulosis, angiocentric immunoproliferative lesions. Extranodal NKfT cell lymphoma, nasal type according to the new WHO classification published in 2001, was relatively common in Asia. It has extremely poor prognosis, the prognostic factor is not well known. Purposes: The purpose of our study was to evaluate prognosis of extranodal NKfT cell lymphoma, nasal type, and to improve treatment outcome of extranodal NKfT cell lymphoma, nasal type. Materials and Methods: We retrospectively analyzed 68 Patients with extranodal NKfT-celis lymphoma, nasal type between 1984 and 2003 in Ajou university hospital and Yonsei university hospital. The study enlolled the patients aged 60 years or less, having B symptoms, serum LDH level, Eastern Cooperative Oncology Group score, International Prognostic Index, Ann Arobr stage. Results: Sixty eight patients were analyzed. 39 patients were male, 29 patients were female. After induction 48% achieved complete remission. The 2-year overall survival rate was 63%. The 5-year overall survival rate was 42.6%. In univariate analysis ECOG, Ann Arbor stage, B symptoms, IPI were significant prognostic factors for CR and survival (p < 0.05). Conclusions: NKfT cell lymphoma has extremely poor prognosis. ECOG, Ann Arbor stage, B symptoms, IPI can be prognostic factors of NKfT cell lymphoma . Modulation of E-cadherin by HGF induces aggressiveness of hypopharyngeal squamous cell carcinoma The 1 st International Symposium on Prognostic Factors in Head and Neck, Salivary and Thyroid Cancer (Leiden, The Netherland: Nov 10-12, 2005) Hepatocyte growth factor (HGF) is known to induce scattering in various epithelial cells, and E-cadherin plays important roles in the maintenance of cell-cell adhesion. However, the mechanisms surrounding these actions are not fully understood. Therefore, we examined how HGF affects the expression and distribution of E-cadherin. In addition, we observed the relationship between prognosis and modulation of E-cadherin by HGF in hypopharyngeal carcinoma. Tumor tissues from 66 patients with hypopharyngeal squamous cell carcinoma (SCC)were evaluated for the expression of HGF, its receptor (c-Met), and E-cadherin. RT-PCR and Western blotting were performed on hypopharyngeal cancer tissues. The association and changes of E-cadherin with HGF treatment in a hypopharyngeal cancer cell line were investigated by RT-PCR, Western blot analysis, inhibition assay, immunofluorescence staining, and invasion assay. E-cadherin expression was found in 87.9% of sces; these could be further classified as membranous type (46.9%) or nonmembranous type (53.1 %). The expression of HGF in tumors with nonmembranous type E-cadherin expression was significantly higher than in tumors with membranous expression. Nonmembranous type E-cadherin expression correlated significantly with lymph node metastasis, distant metastasis, and recurrence (p < 0.05). HGF decreased the expression of E-cadherin and induced the translocation of E-cadherin to the cytoplasm. HGF and E-cadherin neutralizing antibody stimulated dispersion, and HGF significantly enhanced the invasion of hypopharyngeal cancer cells in a dose-dependent manner (p < 0.05). In conclusion, these results suggest that HGF can modulate the expression and intracellular localization of E-cadherin in hypopharyngeal cancer cells. In addition, these results indicate that changes in E-cadherin by HGF can affect the prognosis of hypopharyngeal carcinoma. A new method to determine the causing site of horizontal canal benign paroxysmal positional vertigo ; Bow and Lean test The 29th Annual Midwinter Research Meeting in Association for Research in Otolaryngology (Baltimore, U.S.A. : Feb 5-9,2006) Objectives: Horizontal canal benign paroxysmal positional vertigo (HC-BPPV) accounts for about 10-20% of all patients presenting with BPPV. The cure rate of HC-BPPV by otolith repositioning maneuver is about 60-90% less than those of posterior canal BPPV. One of causes of this low rate is the difficulty of determining the exact causing site for HC-BPPV using Ewald's second law. The purpose of this study is to develop the new method which can easily determine the causing site of HC-BPPV and evaluate its efficiency. Methods: Twenty eight patients with HCBPPV diagnosed in the Dizziness Clinic in Ajou University Hospital, Suwon, Korea, from September, 2004 to September, 2005, were included in this study. The classical method for determining the site is based on comparing the intensity of positioning nystagmus or symptoms in the head positioning test (Ewald second law). The following is the new method. First, we confirm whether the type of HC-BPPV is canalithiasis or cupulolithiasis on supine position. Then we check the direction of nystagmus when the patient bows the head over 900 (bowing nystagmus) and leans the head backward over 450 (leaning nystagmus) on sitting position. For canalithiasis, the causing site is determined as the same direction as that of bowing nystagmus and the opposite direction to that of leaning nystagmus. For cupulolithiasis, the causing site is determined as the opposite direction to that ofnystagmus and same direction as that of leaning nystagmus. In the patients showed different causing site between in the Ewald's second law and in new method, we compared the efficiency of two methods using Barbecue maneuver (BM). Results: In 28 patents (16 cases of canalolithiasis and 12 cases of cupulolithiasis), the patients showed the different causing site between two methods were 11 cases including 7 cases of canaloithiasis and 4 cases of cupulolithiasis. Three of these 11 patients were not completely treated by BM based on the causing site following the Ewald's second law, and then cured by just one trial of BM(opposite direction) based on the new method. The rest 8 cases were easily treated by BM based on the direction following the new method. Just one case did not show any bowing or leaning nystagmus. Conclusions: The bowing and leaning nystagmus (called by 'Choung's method') is a new method which can easily determine the causing site of HC-BPPV. Regulation of intercellular communication through gap junction protein. connexins in immortalized human keratinocytes cells (HaCaT cells). Background and Objectives: Middle ear cholesteatoma needs intercellular communication through gap junctions connexins (Cx) as well as intracellular signal pathway for hyperproliferation. The objectives of this study are to identify regulating materials to control intercellular communication through gap junction proteins Cxs, and to provide basic information to help making in-vitro models for the formation and prevention of middle ear cholesteatoms using immortalized human keratinocytes cells (HaCaT). Materials: H202, acetic acid (AA), dexamethasone, all-trans-retinoic acid (RA), and green tea extracts - epicatechin (EC) and epigallocatechin gallate(EGCG) were used for Cx controlling substances. Methods: To evaluate cytotoxicity of controlling substances, we performed 'neutral red uptake test'. Reverse transcription-polymerase chain reaction (RT-PCR), Western blot, and immunocytochemistry staining were done to identify the change of the connexin (Cx26, 30, 31, 43) expression. 'Scrape load dye transfer assay' (SLOTA) was done to evaluate the intercellular communication of HaCaT cells. Results: Cx26, Cx30, Cx43, and Cx31 in that order were expressed well in HaCaT cells. Through RT-PCR, substances that up-regulated the expression Cx26 mRNA were EGCG(50tJg/ fJ,1), EC, and RA, and the substances that down-regulated Cx26 were AA, H202, EGCG(100tJg/fJ,1). In Western blot, EGCG(50tJg/ fJ,1) up-regulated Cx26 protein, and AA, H202, and dexamethasone down-regulated it. Immunocytochemistry of HaCaT cells showed decreased expression and abnormal location of Cx26 and Cx43 under AA, H202, and EGCG(50 tJg/ fJ,1). SLOTA for functional study showed that acetic acid, H202, and dexamethasone down-regulated intercellular communication, while EC upregulated it. Conclusion: The intercellular communication through gap junction proteins, connexins in HaCaT cells can be easily controlled by several substances. Acetic acid, H202, dexamethasone are considered to be useful substances to inhibit the advancement of middle ear cholesteatomas, and EC may be useful when we are making in vitro cholesteatoma models using HaCaT cells. |
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| 2006 | ||||
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Congenital middle ear cholesteatoma: our experience in 78 cases The 10th Korea-Japan Joint Meeting of Otolaryngology-Head and Neck Surgery (Busan, Korea: Apr 7-8,2006) Background and Objectives: There is an increasing awareness of congenital cholesteatoma in recent decades. The location of the congenital cholesteatoma, when possible initially, can be classified in relation to the four quadrant of the eardrum: anterosuperior and posterosuperior. This study aimed to analyze clinical characteristics of congenital cholesteatoma and facilitate better understanding of its pathogenesis. Materials and Methods: We reveiwed retrospectively 78 patients who were diagnosed as congenital middle ear cholesteatoma under its definite criteria in Ajou University Hospital for the last 11 years(1994-2005). This study was done by analyzing the patients' history, drum finding, temporal bone CT finding, operative finding and pathologic finding. Results: The posterosuperior origin congenital cholesteatoma showed higher degree of hearing loss and more frequent unusual presentation, and detected at an older age than the anterosuperior origin congenital cholesteatoma. The posterosuperior origin congenital cholesteatoma needed more invasive surgery than the anterosuperior origin congenital cholesteatoma. Conclusions: The pathogenesis of congenital cholesteatoma may be different according to its location. The posterosuperior origin congenital cholesteatoma can be explained by epithelial migration theory (Aimi), while the anterosuperior origin congenital cholesteatoma can be explained by epidermoid formation theory (Michael). The diversity of clinical presentation of congenital cholesteatoma requires further study on its pathogenesis. The efficacy of 'Bow and Lean test' for the management of horizontal canal benign paroxysmal positional vertigo The 10th Korea-Japan Joint Meeting of Otolaryngology-Head and Neck Surgery (Busan, Korea: Apr 7-8,2006) Objectives: One problem in the management of horizontal semicircular canal benign paroxysmal positional vertigo (HSC-BPPV) is the difficulty of determining the affected ear using Ewald's second law. The authors developed a new method, 'Bow and Lean Test (BL T)' to more easily determine the affected ear of HSC-BPPV. The purpose of this study was to evaluate the efficacy of BL T for the management of HSC-BPPV comparing the classical method (CM) using Ewald's second law. Methods: Sixty seven patients with HC-BPPV diagnosed in the Dizziness Clinic in Ajou University Hospital, Suwon, Korea between March 2001 and December 2005, were included in this study. We treated the patients using the barbecue rotation (BR) for Cap and BR after vibration (BRA V) for Cup, and we compared the treatment results of both methods. CM was applied to 31 patients (45.6 ±17.1 years) and BLT was applied to 36 patients (48.9±14.2 years). CM is based on Ewald's second law comparing the intensity of nystagmus or symptoms in a head roll test. BL T is based on the directions of both 'bowing nystagmus (BN)'and 'leaning nystagmus (LN)' in the head's bowing and leaning states in a seated position. The affected ear is the same direction of BN in canalolithiasis (Can) and the same direction of LN in cupulolithiasis (Cup). Results: Thirty three cases (31 patients) applied with CM were composed of 24 Can and 9 Cup. In 24 Can, the cured cases were 15 (62.5%) with the first session of BR, 6(25.0%) with the second, and 3(12.5%) with the third. One case showed a switch to Cup type. In 9 Cup, the cured cases were 4 with the first session with BRAV and4 with the second session, and 1 case changed to Cap type. Forty two cases (36 patients) applied with BL T were composed of 29 Can and 13 Cup. Twenty six (90.0%) of 29 Can were successfully treated with the first session of BR, and 3 (10.0%) cases were cured with the second session. Ten (76.9%) of 13 Cup were cured with the first session of BRA V and 2 cases showed a switch to Can type, and 1 case was treated with the fourth session. In 42 cases, 5 (11.9%, 4 Can and 1 Cup) cases did not show a definite affected ear in CM, and 7 (16.7%, 5 Can and 2 Cup) patients showed the different affected ear between two methods. Four (9.5%) cases did not show any BN or LN. Conclusions: BL T (also called 'Choung's test') is very effective in determining the affected ear for the management in HSC-BPPV. Management of cervical necrotizing fasciitis The 10th Korea-Japan Joint Meeting of Otolaryngology-Head and Neck Surgery (Busan, Korea: Apr 7-8,2006) Background and Objectives: Cervical necrotizing fasciitis (CNF) is a rare but potentially lifethreatening soft-tissue infection, primarily affecting the superficial fascial planes. Surgical debridement or incisional drainage is essential for the treatment of CNF. The purpose of this study was to report various causes and courses of the disease, and outcomes of treatment. Patients and Methods: A retrospective chart review of 24 patients treated between January 2000 and February 2007 was performed. All patients were studied with CT scans and treated with intravenous antibiotics. We discuss the history, diagnostic points, and treatment of each patient, and their analysis. Results: Eighteen male and six female patients had an age distribution of 17-81 years. Eight patients had diabetes mellitus, one patient had leukemia, and one patient had Buerger's disease. Four patients died from sepsis, whereas the others were discharged with no complications. Only one was treated with simple aspiration and the others were treated with wide debridement. Wound reconstruction was performed in two patients. Conclusions: Treatment consists of early diagnosis, aggressive surgical debridement, and drainage of the involved necrotic fascia and tissues, together with broad-spectrum intravenous antibiotic coverage . Functional study of regulation for gap junctional intercellular communication by green tea extracts in HNSCC 11th International Congress on Oral Cancer (ICOOC) (Grado, Italy: May 14-17, 2006) Objectives: Reduced expression of connexins (Cxs), gap junction proteins, is frequently reported in various malignant tumors. The anticarcinogenic effects of epicatechin (EC) and epiallocatechin gallate (EGCG), which are major components of green tea, were investigated using a model system of gap junctional intercellular communication (GJIC) in FaDu, hypopharyngeal cancer cell line. Methods: We surveyed Cx isoforms in head and neck cancer cell lines and tissue with RT-PCR and immunohistochemistry. To confirm the effect of EC and EGCG on GJIC, we performed RT-PCR, Western blot, immunofluorescent staining of Cxs using a laser confocal microscope, and scrap loading/dye transfer assay. Results: FaDu cells showed the expression of gap junction protein, Cx26, Cx30, and Cx43. The major connexin in FaDu cells that show response to green tea extracts is Cx 26 and green tea is related to up-regUlation of Cx26 in FaDu cells (dose dependant manner). The intracellular transfer of Lucifer yellow was observed in FaDu cells using scrape-loaded dye transfer technique and its intracellular transfer was increased in epicathecin treated groups (dose dependant manner). Conclusion: Theses results suggest that EC and EGCG may prevent hypopharyngeal cancers by preventing the down-regulation of GJIC during the cancer promotion phase. Significant correlation between serum level of HGF and progression of HNSCC 11th International Congress on Oral Cancer (ICOOC) (Grado, Italy: May 14-17, 2006) Background & Objective: Hepatocyte growth factor (HGF) has known to stimulate motility, invasiveness, proliferation, and morphogenesis of various cells. Recent reports revealed that the growth factor is also related to tumor invasion and metastasis and we already reported that HGF effected on prognosis of hypopharyngeal carcinoma. Material and Methods: To study the role of HGF in the progression of head and neck cancer, HGF levels were measured by an enzyme immunoassay (EIA) system in sera of head and neck cancer patients and followed up the levels after the operation. Results: The mean serum HGF level in 71 healthy control subjects, 78 patients with primary head and neck cancer, and 8 patients with recurrent head and neck cancer were 0.538±0.163, 0.701±0.252, and 0.925±0.349 ng/ml, respectively. The increase of the levels was significantly correlated with the progression of tumor stage. The levels decreased to normal levels 1 month after curative resection of the tumors. However, the levels did not decrease significantly in non resected cases. During the follow-up of the patients for several months, the level was Significantly increased in recurrent head and neck cancer patients, whereas there was no increase in nonrecurrent patients. Conclusion: The serum HGF levels significantly correlated with the aggressiveness of the tumors, suggesting an important role of HGF in the progression of head and neck cancer . The efficacy of 'Bow and Lean Test' for the management of horizontal canal benign paroxysmal positional vertigo XXIV International Congress of Barany Society Meeting(Uppsala, Sweden: Jun 11-14,2006) The relationship between anatomic variations of paranasal sinuses and chronic sinusitis in children The 21 st Congress of the European Rhinologic Society (ERS) & the 25th International Symposium on Infection and Allergy of the Nose (ISIAN) (Tampere, Finland: Jun 11-15, 2006) Objective: Chronic sinusitis is increasing in the pediatric population. Following the initial reports of functional endoscopic sinus surgery (FESS) for children, the majority of patients undergoing this procedure have experienced improved quality of life. Thus, we need to know the precise anatomy and anatomical variations of the nose, as well as the relationship between such anatomy and chronic sinusitis. Patients and Methods: To determine the extent and distribution of disease, as well as associated anatomic abnormalities, computed tomography (CT) scans were performed on 113 children with persistent symptoms of sinusitis after failure of medical therapies. Results: The maxillary sinus was the most commonly involved sinus, followed by the ethmoid, sphenoid, and frontal sinuses. There was no relationship between age and severity of sinusitis. Agger nasi cell was the most common anatomical variation, followed by septal deviation, Haller cell, concha bullosa, paradoxical middle turbinate, and Onodi cell. The prevalence of septal deviation increased with age. There was no significant relationship between the sinusitis and anatomic variations. Conclusions: Anatomical variations in the nose and paranasal sinuses are common in children. Due to the absence of a definitive relationship between anatomical variations and sinus disease, local, systemic or environmental factors appear to be more significant in pediatric sinusitis than the anatomic variations. Functional study of regulation for gap junctional intercellular communication by EGCG and Epicathecin in laryngeal SCC The 4th World Voice Congress (Istanbul, Turkey: Jun 19-24, 2006) Conductive deafness with normal eardrum : absence of the long process of the incus 2006 Meeting of Collegium Oto-Rhino-Laryngologicum Amicitiae Sacrum (Moscow, Russia: Aug 28-30, 2006) Background: A non-progressive and conductive hearing loss with normal eardrum which has no history of trauma and infection is highly suggestive of a congenital ossicular malformation. Among ossicular anomalies, absence of long process of the incus has been sometimes suggested. However, there is a suggestion that this kind of pathology may be due to acute otitis media to which the patients succumbed in their infancy or childhood. This conductive hearing loss with normal eardrum is due to resorption of long process of the incus by its potential inflammation. The purpose of this study is to clarity whether the absence of long process of the incus is caused by inflammation or anomaly. Study design: I experienced 21 cases (5 bilateral cases, 16 unilateral cases) of absence of the incus long process which were confirmed through explotympanotomy at Ajou University Hospital for the last 10 years. Temporal bone CT, operative and histopathologic findings were analyzed. Results: 8 cases showed only absence of the incus long process, among which 5 cases were bilateral. 2 unilateral cases and 1 bilateral case out of 8 cases with absence of the incus long process showed a fibrous band instead of the incus long process. 3 unilateral cases out of 8 cases showed resorptive evidence in the incus body by a possible inflammation such as fibrosis, Harvasian canal widening and osteoclast activity. 13 cases showed absence of the incus long process associated with stapes anomaly, among which 4 cases showed stapes footplate fixation. Conclusions: The most likely cause of the lesion of the incus long process had a possibility of congenital anomaly because many of them were associated with the stapes anomaly. However, I could not completely exclude a possibility of a potential inflammation of this lesion. Green tea extracts inhibits HGF-induced HNSCC progression in vitro 18th EORTC-NCI-AACR International Conference on 'Molecular Targets and Cancer Therapeutics' (Prague, Czech republic: Nov 7-10,2006) Purpose: Aberrant activation of hepatocyte growth factor (HGF) and its receptor, c-Met, has been known to be involved in many human cancer development and progression. During the search for an effective molecule inhibitor of HGF/c-Met signaling, we have found that Epigallocatechin-3-gallate (EGCG), the major bioactive polyphenol present in green tea, might inhibit HGF/c-Met signaling. Studies were performed to address whether EGCG inhibit HGFdependent tumor proliferation and invasion in HNSCC. Method: We performed RT-PCR and Western blot of HNSCC cell line. Proliferation assay, dispersion assay, wound healing assay, and invasion assay were performed in HGF 0,10,30 ng/mL HGF10+EGCG 1IJM, HGF10+EGCG10IJM, HGF30+EGCG1IJM, HGF30+EGCG10IJM. RT-PCR and zymography were performed to examine the roles of MMP-2 and MMP-9, as well as the relationship between HGF and MMPs in FaDu invasiveness. In addition, we confirmed HGF-mediated plasmin activation. Results: Exogenous HGF significantly enhanced the growth of HNSCC cell and this phenomenon was inhibited by EGCG in dose-dependant manner.(p < 0.05) EGCG inhibited HGF-induced scattering of HNSCC cell. EGCG inhibited HGF-mediated migration and invasion of HNSCC cell in dosedependant.(p < 0.05). EGCG inhibits the HGF-Met-uPA-Plasmin network and MMP2, 9. Conclusions: Inhibition of HGF/Met signaling by EGCG leads to decrease of proliferation and invasion in vitro, suggesting the possible use of EGCG in HNSCC associated with downregulation of HGF/Met signaling and the HGF-Met-uPA-Plasmin network and MMP2, 9 . The efficacy of 'Bow and Lean test' for the management of horizontal canal' benignparoxysmal positional vertigo Effect of ototoxic drugs on intercellular communication in cochlear cell line and preventive effects of green tea and gingko biloba extracts The 7th International Academic Conference on Immunobiology in Otorhinolaryngology (Melbourne, Australia: Nov 12-14, 2006) Background and Aims: Inner ear needs intercellular communication through gap junction connexins (Cx) as well as intracellular signal pathway for hearing. Definite ototoxic mechanisms of cisplatin and aminoglycosides have not been well known. Their ototoxic effect may be related with deterioration of intercellular communication in the cochlea. The objectives of this study are to examine the effect of ototoxic drugs on intercellular communication in cochlear cell line (HEI-OC1) and to evaluate the preventive effect of green tea and ginkgo biloba extracts against such a ototoxicity. Methods: To evaluate ototoxicity of gentamicin (GM), streptomycin (SM), and cisplatin, we performed 'neutral red uptake test'. Reverse transcription-polymerase chain reaction (RT-PCR), Western blot, immunocytochemistry staining were done to identify the change of the connexin (Cx26, 29, 30, 31,43) expression. 'Scrape load dye transfer assay' (SLOTA) was done to evaluate the intercellular communication of HEI-OC1 cells. We also carried out the above experiments by treating HEI-OC1 cells with epicatechin (EC), epigallocatechin gallate (EGCG), and ginkgo biloba extracts (GB) before administrating ototoxic drugs. Results: Cx26, Cx30, Cx31 , and Cx43 were expressed in HEI-OC1 cells. Through RT-PCR and Western blot, ototoxic drugs down-regulated the expression of Cxs, and EC (50 1l9/M£) , EGCG (50IJM), and GB (300 IJM) inhibited downregulation effect of these ototoxic drugs. Immunocytochemistry of HEI-OC1 cells showed the decreased expression and abnormal location of Cxs under ototoxic drugs. SLOTA for functional study showed that GM, SM, and cisplatin down-regulated intercellular communication, while EC, EGCG, and GB prevented down-regulation effect of these ototoxic drugs. Conclusion: The intercellular communication through gap junction protein, connexins in cochlear cell line (HEI-OC1 cells) was down-regulated by aminoglycosides and cisplatin, while green tea and Ginko biloba extracts could prevent this deterioration of intercellular communication. Gap junctional intercellular communication may play an important role in ototoxic mechanism of these drugs. Development of new artificial patches to repair traumatic tympanic membrane perforations The 7th International Academic Conference on Immunobiology in Otorhinolaryngology (Melbourne, Australia: Nov 12-14, 2006) Background and Objectives: Perforated tympanic membranes (TM) and otitis media can be managed with a paper patch or tympanoplasty. However, a paper patch is not bio-compatible and tympanoplasty requires aseptic complex surgical procedures. The aim of this study is to develop new artificial eardrum patches using tissue engineering techniques for the treatment of TM perforations. Materials and Methods: We made two kinds of novel bio-compatible patches composed of chitosan water-soluble and water-nonsoluble patches. We made about 50% sized perforations in both TMs in rats. We covered these patches over the right-sided perforations and considered left TMs without any patches as control. We evaluated the healing state of TM perforations and the change of patches at 7, 10, 14, 21 days after applying patches under a microscope. We also analyzed histologic findings of hematoxylin and eosin (H & E) staining and electron microscope. Results: All 18 (100%) TMs with water-soluble patches in 18 young rats showed no perforations in one week, but left control TMs showed healing of 14 (77.8%) in one week and 17 (94.4%) in two weeks. Water-soluble patches were almost resolved within two weeks. Four (21.1%) and 17 (89.5%) TMs with water-nonsoluble patches in 19 adult rats showed no perforations in one and two weeks, respectively. Conclusion: The artificial chitosan patches is more effective than spontaneous healing to repair traumatic TM perforations. The efficacy of 'Bow and Lean test' for the management of horizontal canal benign paroxysmal positional vertigo Management of cervical necrotizing fasciitis The effect of septoplasty on turbinate hypertrophy 2006 Joint Meeting of Eight Departments of Otolaryngology (Taipei, Taiwan: Nov 25-26,2006) Objective: The objective of this study was to measure the effect of septoplasty on the volume of the inferior turbinate in patients with a deviated nasal septum. Design: Prospective analysis. Blind. Patients who underwent septoplasty without turbinate surgery from May 2003 to April 2006 were studied. The thicknesses and cross sectional areas of mucosa and conchal bones were measured using computed tomography (CT) before the operations and at least one year after the operations. Setting: University hospital Patients: A total of 20 patients presenting with a primary complaint of nasal obstruction. Main Outcome Measure: Comparisons of the thicknesses of the medial mucosa, bone, and lateral mucosa and cross sectional area of turbinate before and after septoplasty were performed using the Wilcoxon signed rank test. P values less than .05 were considered statistically significant. Results: The medial mucosa, lateral mucosa, and cross-sectional area of the inferior turbinate on the concave side of the septum were significantly decreased byseptoplasty, and the medial mucosa and cross-sectional area of the inferior turbinate on the convex side of the septum were significantly increased by septoplasty (P < 0.05). The thicknesses and cross-sectional areas of the conchal bone on the concave and convex sides of the septum were not affected by septoplasty. Conclusions: We identified the change of inferior turbinate hypertrophy after septoplasty. And inferior turbinate hypertrophy, especially medial mucosa, may reverse. Turbinate surgery by staged operations after septoplasty may be one of the surgical options in selected cases. |
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| 2007 | ||||
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The effect of septoplasty on turbinate hypertrophy The 26th International Symposium on Infection and Allergy of the Nose, Kuala Lumpur(Kuala Lumpur, Malaysia: Jan 1-4, 2007) Development of water-insoluble chitosan artificial patches to repair traumatic tympanic membrane perforations The 30th Annual Midwinter Research Meeting in Association for Research In Otolaryngology (Denver, U.S.A.: Feb 10-15, 2007) Background and Objectives: Perforated tympanic membranes (TM) and otitis media can be managed with a paper patch or tympanoplasty. However, a paper patch is not bio-compatible and tympanoplasty requires aseptic complex surgical procedures. The aim of this study is to develop new artificial eardrum patches using tissue engineering techniques for the treatment of TM perforations. Materials and Methods: We made a novel bio-compatible patch of which main component is a water-nonsoluble chitosan. We analyzed the mechanical characteristics (tensile strength, elongation rate, toxicity etc) and surface contour with a scanning electron microscope (SEM). In vivo study, we made about 50% sized perforations in both TMs in adult rats. We covered these patches over the right-sided perforations and considered left TMs without any patches as control. We evaluated the healing state of TM perforations and the change of patches at 7, 10, 14, 21 days after applying patches under a microscope. Results: Optimal mechanical characteristics of a water-nonsoluble chitosan patch scaffold was around 0.04mm in thickness, 6MPa in tensile strength, and 107% in elongation, even though the characteristics was very various depending on the components of chitosan and glycerol. SEM showed very smooth surface of a patch. In vivo study, four (21.1 %) and 17 (89.5%) TMs with water-nonsoluble patches in 19 adult rats showed no perforations in one and two weeks, respectively. However, left control TMs showed healing of 0 (0%) in one week and 18 (94.7%) in two weeks. Conclusion: This novel water-nonsoluble chitosan artificial patch is more effective than spontaneous healing to repair traumatic TM perforations. This study was supported by a grant of the Korea Health 21 R&O Project, Ministry of Health & Welfare, Republic of Korea (A06-00043782) Effects of ototoxic drugs on intercellular communication in cochlear cell line (HEI-OC1) and preventive effect of green tea and Ginkgo Biloba Extracts The 30th Annual Midwinter Research Meeting in Association for Research In Otolaryngology (Denver, U.S.A.: Feb 10-15, 2007) Background and Objectives: The ototoxic mechanisms of cisplatin and aminoglycosides may be related with deterioration of intercellular communication in the cochlea. The objectives of this study are to examine the effect of ototoxic drugs on intercellular communication in cochlear cell line (HEI-OC1) and to evaluate the preventive effect of green tea and ginkgo biloba extracts against ototoxicity. Methods: To evaluate ototoxicity of gentamicin (GM), streptomycin (SM), and cisplatin, we performed 'neutral red uptake test'. Reverse transcription-polymerase chain reaction (RT-PCR), Western blot, immunocytochemistry staining were done to identify the change of the connexin (Cx26, 29, 30, 31,43) expression. 'Scrape load dye transfer assay' (SLOTA) was done to evaluate the intercellular communication of HEI-OC1 cells. And we also carried out the above experiments administrating epicatechin (EC), epigallocatechin gallate (EGCG), and ginkgo biloba extracts (GB) to ototoxic drugs in HEI-OC1 cells. Results: Cx26, Cx30, Cx31 , and Cx43 were expressed in HEIOC1 cells. Through RT-PCR and Western blot, ototoxic drugs down-regulated the expression of Cxs, and EC (50~g/M£), EGCG (50IJM), and GB (300 IJM) inhibited down-regulation effect of these ototoxic drugs. Immunocytochemistry of HEI-OC1 cells showed the decreased expression and abnormal location of Cxs under ototoxic drugs. SLOTA for functional study showed that GM, SM, and cisplatin down-regulated intercellular communication, while EC, EGCG, and GB prevented down-regulation effect of these ototoxic drugs. Conclusion: Gap junctional intercellular communication may play an important role in ototoxic mechanism of aminoglycosides and cisplatin. This work was supported by the Korea Research Foundation Grant funded by the Korean Government (MOEHRO, Basic Research Promotion Fund) (KRF-2006-E00081) Modulation of E-Cadherin by Hepatocyte Growth Factor Effects on the Prognosis of HNSCC American Association for Cancer Research Annual Meeting 2007 (Convention center, LA, U.S.A: April 16-20, 2007) Objective: Hepatocyte growth factor (HGF) is known to induce scattering in various epithelial cells, and E-cadherin plays important roles in the maintenance of cell-cell adhesion. However, the mechanisms surrounding these actions are not fully understood. Therefore, we examined how HGF affects the expression and distribution of E-cadherin. In addition, we observed the relationship between prognosis and modulation of E-cadherin by HGF in hypopharyngeal carcinoma. Material and Methods: Tumor tissues from 66 patients with hypopharyngeal squamous cell carcinoma (SCC) were evaluated for the expression of HGF, its receptor (c-Met), and Ecadherin. RT-PCR and Western blotting were performed on hypopharyngeal cancer tissues. The association and changes of E-cadherin with HGF treatment in a hypopharyngeal cancer cell line were investigated by RT-PCR, Western blot analysis, inhibition assay, immunofluorescence staining, and invasion assay. Results: E-cadherin expression was found in 87.9% of SCCs; these could be further classified as membranous type (46.9%) or nonmembranous type (53.1%). The expression of HGF in tumors with nonmembranous type E-cadherin expression was significantly higher than in tumors with membranous expression. Nonmembranous type E-cadherin expression correlated significantly with lymph node metastasis, distant metastasis, and recurrence (p < 0.05). HGF decreased the expression of E-cadherin and induced the translocation of E-cadherin to the cytoplasm. HGF and E-cadherin neutralizing antibody stimulated dispersion, and HGF significantly enhanced the invasion of hypopharyngeal cancer cells in a dose-dependent manner (p < 0.05). Conclusion: These results suggest that HGF can modulate the expression and intracellular localization of E-cadherin in hypopharyngeal cancer cells. In addition, these results indicate that changes in E-cadherin by HGF can affect the prognosis of hypopharyngeal carcinoma. Detection of Helicobacter pylori in middle ear fluids in patients with otitis media with effusion The 9th International Symposium on Recent Advances in Otitis media (Tampa, USA: June 3-7, 2007) Objective: To determine the presence of Helicobacter pylori (H. pylori) in the middle ear fluid of patients with otitis media with effusion (OME) and evaluate possible role of H. pylori in pathogenesis of OME. Design: Prospective clinical trial Setting: Tertiary referral center Methods: The study was performed in 56 patients with OME (25 children and 31 adults) who were referred to Ajou university medical center from Oct. 2005 to Jan. 2007. In all cases, a myringotomy (with or RESEARCH(CON’D) 15 without placement of ventilation tube) was performed. The effusion samples aspirated from the middle ear were analyzed with rapid urease test (RUT) and PCR assay. Results: A total 64 samples from 56 patients were included in RUT and 36 (56.3%) of 64 samples were shown to be H. pylori positive. In PCR assay using 16sRNA primer, a total 31 samples from 25 patients were included and 12 (38.7%) of 31 samples were shown to be H. pylori positive. Both PCR and RUT were carried out in 31 samples. Of 12 PCR-positive samples, 8 (66.7%) were RUT-positive and 4 (33.3%) were RUT-negative. Of 19 PCR-negative samples, 8 (42.1%) were RUT-positive and 11 (57.9%) were RUT-negative. In multiplex PCR assay, a total 16 samples from 16 patients were included and 13 (81.3%) were shown to be H. pylori positive. Of 13 PCR-positive samples, 9 (69.2%) were RUT-positive and 4 (30.8%) were RUT-negative. Of 3 PCR-negative samples, 2 (66.7%) were RUT-positive and 1 (33.3%) were RUT-negative. Conclusions: This study showed presence of H. pylori in the middle ear effusion of patients with OME. These results indicate that H. pylori has a possible role in OME pathogenesis. The role of peroxiredoxin III in the ototoxic drug-induced mitochondrial apoptosis of cochlear hair cell 2007 Meeting of Collegium Oto-Rhino-Laryngologicum Amicitiae Sacrum (Seoul, Korea: Aug 26-28, 2007) Background: Reactive oxygen species (ROS) are important mediators of tissue injury and have been implicated in a number of adverse drug actions. It has also been speculated that ototoxic drugs exert their adverse cochlear side effects by free radical generation. The mitochondria are an important site for the production of cellular ROS. Aberrant increases in mitochondrial ROS can induce apoptosis by causing the release of proapoptotic factors from the mitochondria. Cells contain a variety of peroxidases including catalase, glutathione peroxidase, and peroxiredoxin (Prx). The newly identified Prx family of peroxidase includes at least six isoforms in mammalian cells. Among them, Prx III is synthesized with a mitochondrial targeting sequence and is then transferred to mitochondria. The aim of this study is to reveal the role of Prx III in the ototoxic druginduced mitochondrial apoptosis of cochlear hair cell. Study design: With the use of RNA interference (RNAi), the effects of depletion of Prx III on the ototoxic drug-induced apoptotic events in UB/OC (University Bristol/Organ of Corti) cell line were investigated. Results: Cisplatin or gentamicin induced accumulation of H2O2 in the mitochondria. The mitochondrial generation of H2O2 contributes to apoptotic signaling independently of the direct contribution of O2-. The rates of mitochondrial membrane potential collapse, cytochrome c release, and caspase activation increased in Prx III-depleted cells. Conclusions: These results suggest that Prx III is a critical regulator of the abundance of mitochondrial H2O2, and that cisplatin-, and gentamicin-induced apoptosis were related to mitochondria-dependent pathway through interaction with H2O2 and Prx III. Green tea extracts induces apoptosis and inhibit HGF-induced HNSCC progression in vitro European Cancer Conference 14 (Barocelona, Spain: September 23-27, 2007) Purpose: Activation of hepatocyte growth factor (HGF) and its receptor, c-Met, has been known to be involved in many human cancer development and progression. During the search for an effective molecule inhibitor of HGF/c-Met signaling, we have found that Epigallocatechin-3-gallate (EGCG), the major bioactive polyphenol present in green tea, might inhibit HGF/c-Met signaling. Studies were performed to address whether EGCG inhibit HGF-dependent tumor proliferation and invasion in HNSCC. Method: We performed RT-PCR and Western blot of HNSCC cell line. Proliferation assay, dispersion assay, wound healing assay, and invasion assay were performed in HGF 0, 10, 30 ng/mL HGF10+EGCG 1μM, HGF10+EGCG10μM, HGF30+EGCG1μM, HGF30+EGCG10μM. RT-PCR and zymography were performed to examine the roles of MMP-2 and MMP-9, as well as the relationship between HGF and MMPs in FaDu invasiveness. In addition, we confirmed HGF-mediated plasmin activation. We performed Tunnel assay, DNA fragmentation analysis, Annexin V staining, and FACS analysis for apoptotic effect of EGCG in HNSCC. Results: Exogenous HGF significantly enhanced the growth of HNSCC cell and this phenomenon was inhibited by EGCG in dose-dependent manner.(p < 0.05) EGCG inhibited HGF-induced scattering of HNSCC cell. EGCG inhibited HGF-mediated migration and invasion of HNSCC cell in dosedependent.(p < 0.05). EGCG inhibits the HGF-Met-uPA-Plasmin network and MMP2, 9. We confirmed EGCG induced apoptotic phenomenon in Tunnel assay, Annexin V staining, DNA fragmentation analysis and FACS. Conclusions: Inhibition of HGF/Met signaling by EGCG leads to decrease of proliferation and invasion in vitro, suggesting the possible use of EGCG in HNSCC associated with downregulation of HGF/Met signaling and the HGF-Met-uPA-Plasmin network and MMP2, 9. Bone density of facial bone in Osteoporosis 12th Congress of the international rhinologic society (Venezia, Italy: Dec 5-8, 2007) Osteoporosis is a systemic skeletal disorder characterized by reduced bone mineral density. In the facial bone, osteoporosis can occurs in both the maxilla and the mandible. In rhinoplasty, osteotomy is very common procedure in the nasal bone and the maxilla. There has been increasing chances performing osteotomy of osteoporosis patients because of changing to aging society. But, there were few studies on osteoporosis in the maxilla and the nasal bone. The purpose of our study is comparing the facial bone density between normal and osteoporosis, considering stability of the facial bone in osteoporosis. A total of 24 osteoporosis patients and 44 controls who underwent both Osteomeatal unit computerized tomography (OMU CT) scans of Dual-Energy X-ray Absorptiometries (DEXA) were included in this study. The Hounsfield unit (HU) was measured at the sites of medial and lateral osteotomies. In the maxilla, osteoporosis group had significantly decreased HU values than control group (Rt; 1094.89 ± 172.73 vs. 1362.80 ±169.06, P < 0.001, Lt; 1102.90 ± 146.75 vs. 1330.30 ± 183.39, P < 0.001). In the nasal bone, osteoporosis group had significantly decreased HU values than control group (Rt; 426.43 ± 123.55 vs. 534.70 ± 126.89, P < 0.001, Lt; 470.92 ± 122.23 vs. 571.88 ± 149.72, P < 0.006).The HU values were significantly different between the nasal bone and the maxilla (553.29 ± 139.23 vs. 1346.55 ± 176.12, P < 0.001). CT is a useful tool to determine the bone density of the concerned areas. Osteoporosis group has lower bone density than normal group in the facial bone. Care may be needed in osteotomy of osteoporosis patient. |
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Detection of Highly-Reactive Oxygen Species (hROS) in Rat Organ of Corti Treated with Gentamicin The 31st Annual MidWinter Research Meeting in Association for Research in Otolaryngology (Phoenix, USA: Feb 16-21, 2008) Background and Objectives: Reactive oxygen species (ROS) are thought to be involved in aminoglycoside induced hair cell (HC) loss. Two new probes, aminophenyl fluorescein (APF) and hydroxyphenyl fluorescein (HPF) are selective dyes for the detection of hROS (-OH, ONOO-,-OCl) in living cells. These probes were used to detect hROS in the cells of neonatal rat organ of Corti (oC) after gentamicin exposure In Vitro and to examine the relationship between cell death and the formation of hROS. Materials and Methods: hROS formation was examined in two conditions. In the first, explants of basal, middle or apical turn oC from p3 Sprague-Dawley rats were maintained in Dulbecco’s modified Eagle’s medium (DMEM) and exposed to gentamicin (50 μM) for 24, 48, or 72 hours. The explants were concurrently treated with APF (15 μM) or HPF (7.5 μM) and their fluorescence was documented. In the second experiment, explants were exposed to higher levels of gentamicin (0.5 and 1 mM), and observed at 0, 2, 10, 20, 40, 60 and 80 minutes. Formation of hROS was compared with HC loss across cochlear turns by co-labeling with phalloidin and DAPI after fixation. The sensitivity of HPF and APF for the detection of hROS was compared by analysis of cell number and fluorescence intensity. Results: In the first study, hROS formation was initially detected in HCs of the basal and middle turn oC exposed to 50 μM gentamicin at 48 hours, with an increase in hROS at 72 hours. The formation of hROS at 48 hours was restricted to outer HCs (OHCs), and occurred before the loss of HC stereocilia. At 72 hours, OHCs that had lost their stereocilia showed hROS, and formation of hROS in a few inner HCs (IHCs) was noted. Very little formation of hROS was observed in apical turn explants, even at 72 hours. In the second experiment, formation of hROS was first detected at 10 minutes primarily in first row OHCs and IHCs, and remained constant for 80 minutes. No HC loss was observed by 80 minutes. In both experiments, APF was more sensitive than HPF in detecting hROS. Conclusion: The generation of hROS appears to be an important initial step in gentamicin-induced hair cell death. The differential sensitivity of basal and middle turn HCs appears to be related to differences in hROS formation, with very little formation in apical HCs. Low dose gentamicin In Vitro produce patterns of hROS formation that are similar to HC loss produced by gentamicin in vivo. The effects of antioxidants on hROS formation in HCs, as well as In Vivo studies, are in progress. 2009 Basic research related to pathogensis of middle ear cholesteatoma: reversibility of its hyperproliferative character The 12th Korea-Japan Joint Meeting of Otolaryngology-Head & Neck Surgery (Nara, Japan: Apr 3-4, 2008) Epidermal homeostasis is maintained by a delicate balance between proliferation and terminal differentiation. Cholesteatoma is characterized by the presence of a squamous epithelium invading the middle ear cavity, which is believed to have hyperproliferative properties. From a histological point of view this pathological tissue is composed of two integrated parts-matrix and peri matrix. The interaction between cellular components is essential for the major histopathological features of cholesteatoma-hyperproliferation and bone destruction. The proliferation and differentiation of cells in cholesteatomas and expression of their properties are under the control of a large number of regulatory processes and complex interactions called inter-and intracellular signal transduction as well as apoptosis. One of the major goals in cholesteatoma study is to estimate its hyperproliferative potential. For the last 15 years, many studies about hyperproliferative character of human and experimental cholesteatomas have been done in my laboratory. I could confirm that the epithelium of cholesteatoma proliferates at a higher rate than in external auditory canal and retroauricular skins, suggesting that extensive accumulation of keratinous mass may induce changes in cellular differentiation and proliferation. I also could confirm that some cholesteatomas, especially cholesteatoma in the early stage, might be managed with only minimal treatment such as control of inflammation and maintenance of adequate ventilation. Congenital stapes anomaly with normal eardrum The 2nd International Symposium of the Politzer Society on Otosclerosis and Stapes Surgery(France: May 8, 2008) Objectives: A non-progressive and conductive hearing loss with normal eardrum, which has no history of trauma and infection, is highly suggestive of a congenital ossicular malformation. Among ossicular anomalies, stapes anomaly is the most common, and it is clinically important because hearing loss can be corrected by appropriate procedures. The purpose of this study is to describe patterns of stapes anomaly and to analyse its surgical result with special reference to the patterns of stapes anomaly. Methods: I experienced 41 cases(47 ears) of congenital stapes anomalies which were confirmed through the explotympanotomy at Ajou University Hospital for the last 12 years. The preoperative and postoperative audiological findings, temporal bone CT finding, and operative finding were analysed. Results: There were 14 anomalous patterns of the stapes among which footplate fixation was the most common anomaly. I classified these patterns of the stapes anomaly into 6 types according to the status of the footplate. I could get hearing improvement in 63.8% of my cases after stapes surgery. Conclusions: Footplate fixation was usually bilateral, while anomalies associated with incus anomaly were unilateral. The success of the surgical treatment of stapes anomaly might depend on developmental status of the footplate and oval window. Stapes anomalies were detected without a certain rule of patterns, and big variety of those patterns can be detected again in the future . Otitis media with effusion: is it precursor? The 8th International Conference on Cholesteatoma & Ear Surgery(Antalya, Turkey: Jun 16-20, 2008) Middle ear cholesteatoma occurs as two principle different entities: congenital and acquired. The latter is divided further into the primary acquired or attic retraction pocket cholesteatoma and the secondary acquired cholesteatoma, which it occurs due to epithelial migration into the middle ear at the site of a tympanic membrane perforation or iatrogenically implanted during an otologic surgery. We need to consider whether there is relationship between OME and congenital or attic retraction pocket cholesteatoma or not. First, we could often find that cholesteatoma comes with OME in our experience about 30% of congenital cholesteatoma. Squamous metaplasia of the inflamed middle ear epithelium is not uncommon. Therefore, the inflammatory condition such as recurrent OME might play an important role in squamous metaplasia of middle ear epithelium and, under that condition, we could easily expect that cholesteatoma may be caused by accumulation of keratin. Second, Retraction pocket, which is occasionally known as precursor of cholesteatoma (but not all the time), is one of many complications associated with tympanostomy tube insertion or with recurrent and persistent OME for lack of prompt and effective medical treatment. Though sequelae of OME are uncommon if proper medical treatment fulfilled, we should not forget that OME may be precursor of cholesteatoma and the diversity of clinical presentation of OME requires further study focused on its correlation with cholesteatoma. Bone resorption in cholesteatoma: the role of the osteoclast The 8th International Conference on Cholesteatoma & Ear Surgery(Antalya, Turkey: Jun 16-20, 2008) Cholesteatoma of the middle ear may lead to the destruction of the middle and inner ear structures, resulting in hearing loss, vestibular dysfunction, facial paralysis, as well as lethal intracranial complications. The mechanisms causing bone destruction by cholesteatoma include, the pressure effect of cholesteatoma, secretion of enzymes by granulation tissue, release of cytokines by inflammatory cells, and the activation of the osteoclast. Studies over the last 10 years, however, have reported conclusive evidence that bone resorption due to cholesteatoma is solely the consequence of osteoclast resorption. As such, the potential role of the osteoclast in cholesteatoma-induced bone destruction must observed. The complex interaction of factors that triggers osteoclasts is not fully known. The possible role of exogenous and endogenous factors has been studied in recent years. One of the most important exogenous factors is lipopolysacharide(LPS), a membrane component of Gram-negative bacteria. In more recent studies. Bone resorption was demonstrated in co-cultures of osteoclasts and osteoblasts in the presence of LPS. LPS may stimulate osteoclastic bone resorption directly and indirectly by inducing maturation of preosteoclastic cells. LPS is involved in the indirect pathway by stimulating the production of bioactive factors or mediators. These factors are related enzyme and cytokines such as the matrix-metalioproteinases(MMPs), transforming growth factor-beta 1 (TGF-beta 1), tumor necrosis factor-alpha(TNF-alpha), interleukin-1(IL-1), nuclear factor-kappa B ligend(RANKL)and receptor activator of nuclear factor-kappa B(RANK). Almost all of them are overexpressed in cholesteatoma and they are associated with bone destruction. The pathologic activation of the osteoclast in cholesteatoma is often associated with chronic inflammation and is mediated by the elaboration of pro-inflammatory cytokines. A variety of factors released during inflammation and local pressure and known to influence osteoclast-mediated bone resorption under pathologic conditions, include interleukins, tumor necrosis factor-a, interferon-[3, prostaglandin, growth factor, neurotransmitters, and nitrate oxide, among others. Though osteoclast bone resorption is initiated from a cascade of molecular events, osteoclast development and resorption is a final common pathway in cholesteatoma-induced bone destruction. Therefore, further studies about biological control of the osteoclast are essential to understanding the pathophysiology and treatment of cholesteatoma. Tracking recurrent and residual cholesteatoma The 8th International Conference on Cholesteatoma & Ear Surgery(Antalya, Turkey: Jun 16-20, 2008) Although Many ENT surgeons treat cholesteatoma by a canal wall up mastoidectomy (CWUM), as part of a multistep surgical strategy, cholesteatoma treated with CWUM has been recognized as having a high rate of residual and recurrent cholesteatoma, in the range of 29% or higher. Therefore, after surgery of cholesteatoma it is important to notice whether cholesteatoma is recurred and residual or not. Recurrent or residual cholesteatoma could be suspected by clinical suspicion and careful physical examination, but if radiologic imaging used we could give more exact diagnosis of this disease and get more information about its conditions. Radiologic evaluations widely used are principally CT and MRI. CT is very effective tool for information on on, delineation of the tympanic segment of the facial nerve, bony erosion and anatomical features, but has limited value for information on soft tissue thickening in the surgical cavity. Although Magnetic resonance imaging (MRI) takes a merit of better tissue differentiation by using different types of sequences, MRI is occasionally used in otologic middle ear surgery for further characterization of soft tissues and description of possible complications. We could well know that MRI is more excellent than CT in detection of soft tissue lesion, such as residual or recurrent cholesteatoma, but couldn't be able to diagnose as residual or recurrent cholesteatoma with only MRI because of its poor sensitivity. Therefore, the diagnosis of recurrent or residual cholesteatoma should be determined by combination of surgeon' experience, radiologic imaging and careful physical examination. Congenital middle ear cholesteatoma: our experience in 106 cases The 8th International Conference on Cholesteatoma & Ear Surgery(Antalya, Turkey: Jun 16-20, 2008) Objectives: To analyze clinical characteristics of congenital middle ear cholesteatoma according to its location and gross-pathological type and to facilitate better understanding of its pathogenesis. Method: We reviewed retrospectively 106 patients who were diagnosed as congenital cholesteatoma in the middle ear under its definite criteria in Ajou University Hospital for the last 13 years(1994-2007). This study was done by analyzing the patient's history, drum finding, temporal bone CT finding, pathologic and operative findings. Results:The posterosuperior origin of congenital cholesteatoma is more common than the anterosuperior origin. The posterior mesotympanic cholesteatoma showed relatively larger size and older age when diagnosed, higher degree of hearing loss, and more frequent unusual presentation than the anterior origin. The opentype congenital cholesteatoma which usually originated from posterosuperior portion of the mesotympanum detected at an older age than the cystic type. 30 cases (28.3%) with congenital cholesteatoma were associated with OME, which was detected more common in the posterior origin. The residual lesion was detected in 8 cases (7.5%), which was more common after tympanotomy. Conclusion: The pathogenesis of congenital cholesteatoma may be different according to its location and pathologic type. The diversity of clinical presentation of congenital cholesteatoma requires further study on its pathogenesis . Isolated congenital ossicular anomaly 2008 Annual Meeting of CORLAS (Berlin, Germany: Aug 24-28, 2008) Background: A nonprogressive and conductive hearing loss in the range of 40 to 60dB with normal tympanic membrane which has no history of trauma or infection is highly suggestive of a congenital ossicular malformation. Stapes anomaly is the most common among the ossicular anomalies, and they are clinically important because hearing loss can be corrected by appropriate procedure. The purpose of this study is to describe patterns of the ossicular anomaly encountered in patents who have a normal eardrum, and to analyse its surgical result with special reference to its patterns. Study design: I experienced 78 cases(94 ears) of congenital ossicular anomaly which were confirmed through the explotympanotomy for the last 20 years. The preoperative and postoperative audiologic findings, operative findings and temporal bone CT findings were analysed. Results: There were 20 anomalous patterns of ossicular anomaly among which stapes footplate fixation was the most common anomaly. I classified congenital ossicular anomaly into 5 types according to the status of the stapes footplate. Stapes footplate fixation was the most common type which was usually bilateral, while anomalies associated with incus and malleus were usually unilateral. I could get hearing improvement in 72.3% of my cases after surgery. Conclusions: There were a great diversity of patterns of ossicular anomaly, which were detected without a certain rule of pattern and big variety of those patterns can be detected again in the future. The success of surgical treatment of congenital ossicular anomaly might depend on the status of the stapes footplate . Absence of the long process of the incus with normal eardrum: congenital or postinflammatory? The 18th Annual Meeting of Japan Otological Society(Kobe, Japan: Oct 15-17, 2008) Introduction: The long process of the incus is derived from branchial arch II as well as the superstructure of the stapes. Congenital absence of the long process of the incus shows a nonprogressive and 40-60 dB conductive hearing loss with a normal eardrum. However, this conductive hearing loss may be due to resorption of the long process of the incus by its potential inflammation: acute otitis media during infancy or childhood. The reasons why the long process of the incus is vulnerable to inflammation are its poor blood supply and floating structure in the middle ear space. Another possible cause is remodeling of the incus through its repeated resorption and regeneration. The aim of this study was to clarify whether the absence of the long process of the incus is caused by inflammation or anomaly. Materials and Method' I already published 21 cases with absence of the long process of the incus(Acta Oto-Laryngologica, 2007;127:816-820). I added 4 more cases, which were analysed through temporal bone CT and operative findings. Result: Added cases showed a more strong evidence of the possibility of the potential inflammation of this lesion. Conclusion: The most likely cause of a lesion with an absence of the long process of the incus was congenital. However, the possibility of a potential inflammation of this lesion can not be completely excluded, especially in cases with an absence of the superstructure of the stapes not associated with its footplate fixation. Present status of research on otitis media 1 st Asean Academy of Neurotology, Otology & Audiology Congress (Manila, Philippine: Nov 28, 2008) Otitis media has been one of the most prevalent form of otological diseases. However, recently, acute otitis media has much variety in its pathogenic pattern of mechanism owing to environmental change. Also, the incidence of chronic otitis media has decreased owing to better economic status and health care. Thus, cases of middle ear surgery have decreased relatively in number. The pathogenesis of otitis media is not clearly understood, but there are abundant epidemiological and clinical evidences in support of the idea that eustachian tube dysfunction is an important predisposing factor in the pathogenesis of otitis media. In recent years, a special interest has been focused on the mucosal biology of the eustachian tube that is related to the protection of the middle ear from infection and the formation of the middle ear effusion. Numerous laboratory and clinical data support the notion that local defense mechanisms, in addition to systemic immunity, protect the tUbotympanum from invading organisms. The eustachian tube is protected by the mucosal defense system common to all mucous membranes. In this presentation, I will review otitis media as an immunologic disease on the basis of current research work-ups. I will focus on the role of viruses and bacterias in otitis media including otitis media as a biofilm disease. In conclusion, future directions of otitis media research is to understand fully the molecular mechanisms involved in bacteria-host cell interaction, and the characterize the cell and molecular biology of the eustachian tube and middle ear. Finally, we have to need to develop innovate therapies using new technologies for preventing and treating otitis media. Generation of highly-reactive oxygen species is correlated with hair cell damage in organ of Corti treated with Gentamicin 1 st Asean Academy of Neurotology, Otology & Audiology Congress (Manila, Philippine: Nov 28, 2008) Reactive oxygen species have been suggested to play a major role in aminoglycosideinduced hair cell (HC) loss, but are difficult to detect. Moreover, reactive oxygen species occur normally in cells, where they have roles in metabolism, cell signaling and other processes. Two new probes, aminophenyl fluorescein (APF) and hydroxyphenyl fluorescein (HPF) are dyes which selectively detect highly reactive oxygen species (hROS), the species most associated with cellular damage. We assessed hROS formation in the neonatal rat organ of Corti (OC) during chronic exposure to 50 !-1M gentamicin (GM) in vitro,to examine the relationship between cell damage and hROS formation across HC type and across the three cochlear turns. hROS formation wa sinitially detected at 48h, with an increase at 72h. At 48h, hROS were restricted to outer HCs(OHCs), and occurred prior to loss of stereocilia. At 72h, OHCs showed both hROS and stereocilia loss, and hROS were noted in a few inner HCs(IHCs). Basal turn HCs showed more hROS formation than middle turn HCs. Very little hROS formation or stereocilia loss was observed in the apical turn, even at 72h. First row OHCs were most vulnerable to GM-induced hROS, followed by second and then third row OHCs. IHCs behaved similarly to third row OHCs. The resul!s suggest that hROS formation is an important initial step in GM-induced HC damage. Moreover, the differential sensitivity of HCs in the OC appears to be closely related to differences in hROS formation. The usefulness of Bow and Lean test as a tool of lateralization of horizontal canal benign 1 st Asean Academy of Neurotology, Otology & Audiology Congress (Manila, Philippine: Nov 28, 2008) paroxysmal positional vertigo Objectives: 'Bow and Lean test (BLT) (also called Choung's test), which we developed in the previous study (Laryngoscope, 2006), is a new method for determining easily the affected ear of horizontal semicircular canal benign paroxysmal positional vertigo (HSC-BPPV). The purpose of this study is to evaluate the efficiency of BL T for diagnosis and management of HSC-BPPV. Materials and Methods: Two hundred seven cases were divided into two groups, BL T or classic method groups according to the method determining the affected ear. We evaluated expression rates of bowing or leaning nystagmus, and compared the resolution rates between two groups. The patients were treated with canalith repositioning procedures (CRP) depending on the affected sites following BL T in the BLT group (n=164) and head roll test (HRT) alone in the classic method group (n=43). Results: In the classic method group, 22 (73.3%) of canalolithiasis type (n=30) and 9 (69.2%) of cupulolithiasis type (n=13) were cured by the second session of CRP. In the BL T group, 126 (76.8%) cases showed bowing and/or leaning nystagmus. By the second session of CRP, 74 (83.1%) of canalolithiasis type (n=89) and 56 (74.7%) of cupulolithiasis type (n=75) were cured. Thirteen (76.5%) of 17 cases showing similar intensity nystagmus in HRT and 22 (78.6%) of 28 cases who showed different affected ears between two methods were cured by the second session of treatment, respectively. Conclusions: BL T is a useful method to determine easily an affected ear in HSC-BPPV, especially when localization is uncertain under the classic HRT . Gingko Biloba Extract(EGb761) prevent cisplantin-induced apoptosis & down-regulation of gap junctional intercellular communication in auditory hair cells The 32nd annual Midwinter Research Meeting in Association for Research In Otolaryngology (Baltimore, U.S.A. :Feb 14-19, 2009) Purpose: Cisplatin is a well-known anticancer drug showing apoptosis and disturbance of gap junctional intercellular communication (GJIC) in auditory hair cells, which is an important process in organ of Corti (0C) for hearing. Gingko biloba extracts (EGb 761) has been used as an antioxidant or a circulation enhancer. The purpose of this study was to examine the efficiency of EGb 761 in protecting against cisplatin-induced apoptosis and disturbance of GJIC. Materials and Methods: For evaluation of anti-apoptotic action of EGb, HEI-OC1 cell line was cultured and treated with cisplatin (50uM) with EGb 761 (300ug/ml) for 24 hrs, and then immunocytochemistry (annexin V/propidium iodide) and Western blotting (caspase 3, PARP) were done. And basal turn oC explants from neonatal (p3) rats were exposed to cisplatin (1-10uM) and EGb (50 - 400ug/ml). The number of intact hair cells was counted by co-labeling with phalloidin, MyoVlla, and DAPI. For evaluation of GJIC, immunocytochemistry and Western blot of connexins (Cxs) and scape loading dye transfer (SLDT) were tested for intracellular location, connexin change, and GJIC on HEI-OC1 cells. Results: EGb prevented cisplatin-induced apoptosis in immunostaining and decreased caspase 3 and PARP bands, which were increased in cisplatin-treated cells in Western blot. In oC explants, EGb significantly prevented cisplatin (6uM, 10uM)-induced hair cell damage compared with cells treated with cisplatin alone. In this experiment, the number of phalloidin staining was less than that of MyoVlla in the same situation. In connexin study, EGb prevented abnormal intracellular locations of Cx 26, 30, 31, 43 in cells treated with cisplatin in immunocytochemistry and increased Cx bands, which were decreased by cisplatin in Western blot. EGb also prevented cisplatin-induced disturbnace of GJIC in SLOT study. Conclusions: EGb 761 prevent cisplatininduced apoptosis and disturbance of GJIC in auditory hair cells. EGb 761 may be one of preventive medications against cisplatin induced ototoxicity. This study was supported by the Korea Research Foundation Grant funded by the Korean Government (MOEHRO, Sasic Research Promotion Fund)(KRF-2006-E00081). Intracellular mechanisms of gentamicin-induced hair cell damage in neonatal rat organ of Corti The 32nd annual Midwinter Research Meeting in Association for Research In Otolaryngology (Baltimore, U.S.A. :Feb 14-19, 2009) Purposes: Apoptosis mediated by reactive oxygen species (ROS) and intracellular signaling pathways is thought to playa role in gentamicin (GM)-induced cochlear hair cell loss, however the mechanisms that mediate this have not fully elucidated. The purpose of this study was to assess the significance of intracellular processes, including highly-reactive oxygen species (hROS) formation, JNK pathway activation and apoptosis, in damage to hair cells in the organ of Corti (oC) after treatment with GM. Materials and Methods: Sasal turn oC explants from postnatal day 3 (p3) or p4 rats were cultured and exposed to GM (35uM) combined with several concentrations of glutathion (GSH, ROS inhibitor), Clostridium difficile toxinS (COTS,JNKinhibitor), ZVAO-FMK (caspaseinhibitor), or combined inhibitors for48hours.Hair cells was assessed morphologically by co-labeling with phalio.id in,MyoVlla, and OAPI. The involvement of each pathway was evaluated by staining for hROS, phospho-c-JNK, or activated caspase3. Results: GSH, COTS, or ZVAO-FMK significantly inhibited hair cell damage in a dose-dependent manner, when compared with GM alone. When the explants were exposed to inhibitor combinations, the use three inhibitors simultaneously significantly protected hair cell loss, compared with combinations of two inhibitors. hROS formation was also significantly inhibited in GSH- or COTS-treated oCs. Caspase 3 activation was decreased most effectively in ZVAO-FMK-treated oCs, followed by GSH, but not in COTS-treated explants. COTS inhibited GM-induced JNK activation more effectively than GSH or ZVAO. Conclusions: hROS formation, activation of the JNK pathway, and caspase activation are each involved in GM-induced damage to oC hair cells. hROS formation appears to be linked to the activation of both the JNK pathway and caspase 3. However, caspase activation may be less dependent on JNK activation, suggesting alternative pathways to hair cell death. The combined use of three inhibitors against ROS formation and the activation of both JNK and caspase 3 showed more effective protection effect against GM-induced hair cell damage that single use of inhibitors, also suggesting that these mechanisms are not completely overlapping. Managements for lateral sinus thrombosis; does it need the ligation of internal jugular vein or anticoagulants? 9th Asian-Oceanian International Congress on Skull Base Surgery(Busan, South Korea, Nov 6-8, 2008) Objective: The lateral sinus thrombosis (LST) obviously requires a prompt mastoid surgery with antibiotics for definitive management, however, the ligation of internal jugular vein (IJV) and use of anticoagulatns in the management of LST are still controversial issues. The purposes of this study were to review the clinical characteristics and treatment outcomes of patients with LST and to discuss the need of IJV ligation or anticoagulants. Methods: We retrospectively reviewed the charts of five patients with LST from 2003 to 2006. Clinical symptoms, imaging findings, clinical course, treatments, prognosis, and complications were reviewed. Results: One male and four female patients had a mean age of 37 years (range; 8 to 65 years). The chief complaints were otalgia, fever, mastoid tenderness, and neck pain. All patients were confirmatively diagnosed with Magnetic Resonance Image - Venography or Angio - Computerized tomography scans. The patients were treated with appropriate antibiotics and operations including mastoidectomies according to their suspected disease course. The authors did not perform the ligation of IJV and use anticoagulants in all cases, but there were no mortalities or morbidities. Conclusion: Although LST is a disease with high mortality, it can be treated with appropriate antibiotics and early operation according to a disease course, without any complications. IJV ligation and use of anticoagulants do not seem to be essential procedures for the management of LST, and it should be carefully considered according to the extents of disease and the state of patients . Effect of septoplasty on inferior turbinate hypertrophy 22nd ERS & 27th ISIAN (Jun 13-20, Crete, Greece) Objective: To measure the effect of septoplasty on the volume of inferior turbinate in patients with a deviated nasal septum. Design: In this retrospective analysis, patients who underwent septoplasty without turbinate surgery from May 1, 2003, through April 30, 2006, were stUdied. The thicknesses and cross-sectional areas of mucosa and conchal bones were measured with computed tomography before the operations and at least 1 year after the operations. Setting: University hospital. Patients: A total of 20 patients who presented with a chief concern of nasal obstruction. Main outcome measures: The thicknesses of the medial mucosa, bone, and lateral mucosa and the cross-sectional area of turbinate before and after septoplasty were compared using the Wilcoxon signed rank test. P < .05 was considered statistically significant. Results: The medial mucosa and cross-sectional area of the inferior turbinate on the concave side of the septum were significantly decreased by septoplasty (both, P = .01), and the medial mucosa and cross-sectional area of the inferior turbinate on the convex side of the septum were significantly increased by septoplasty (P = .01). The thicknesses and cross-sectional areas of the conchal bone on the concave and convex sides of the septum were not affected by septoplasty. Conclusion: After septoplasty, inferior turbinate hypertrophy, especially in the medial mucosa, may reverse. Concurrent BPPV in patients with vestibular neuritis The 12th Japan-Korea Joint Meeting of Otorhinolaryngology H & N surgery (Nara, Japan: Apr 3-5, 2008) Objective: to investigate the causal relationship between benign paroxysmal positional vertigo (BPPV) and vestibular neuritis (VN) by examining the presence and characteristics of BPPV that concurrently occurred in the patients with VN. Study Design: A prospectively designed study. Patients & Method: This study included 60 patients with VN that were diagnosed at the Emergency center, Ajou University Hospital, Suwon, Korea from April 2006 to March 2008. As part of our battery of clinical neurotological examinations, computer analYSis of ENG recordings was routinely performed. Video-oculographic recording included spontaneous nystagmus in the primary position of the eye and positional testing. Provocation test for positional vertigo was done within 3 days of initial diagnosis of VN. Results: Twenty (33.3%) of the 60 patients diagnosed with VN had BPPV within 3 days after the onset of vertigo. Among these 20 patients, 17 (28.3%) patients had VN and BPPV occurring in the same ear, while the other 3 patients had VN and BPPV occurring in the opposite ear. All patients with concurrent BPPV were treated successfully with canalith repositioning maneuver. Conclusion: About 30% of the patients with VN had concurrent BPPV. This result emphasizes the need not to neglect the possibility of BPPV in the patients with VN . Development of anticancer agents using bioactive products of marine Bacillus spp. in head and neck cancer American Association for Cancer Research Annual Meeting 2009 (San Diego, U.S.A.: Apr 11-18, 2008) Background: H31 is a new anti-tumor material that were originally discovered in marine Bacillus spp. H31 has demonstrated powerful anticancer effect against panel of human hypopharyngeal SCC(FaDu), oral cavity SCC(KB), larynx SCC(SNU1066), gastric cancer(SNU1, 16) at very low concentrations. In this study, we investigated the effect of H31 as a chemopreventative or therapeutic agent in head and neck cancer. Method : We finally found 5(1514) candidate materials from marine microbial extracts in anti-cancer drug screening by MTT assay. We investigated the effect of H31(one of the candidates) on HGF-induced proliferation, dispersion, invasion, and expression of MMPs(by RT-PCR, zymogram) and induction of apoptosis(by DNA fragmentation assay, FACScan with Annexin V-FITC) in FaDu cells, a hypopharyngeal cancer cell line. And we analyzed signal pathway of H31 and evaluated neurotoxicity in vivo zebrafish model. Results : H31 is originated from novel marine Bacillus spp. (similarity 95% with Bacillus spp by gene sequencing). H31 inhibited HGF-induced scattering, migration, invasion and MMP-2 activity of hypopharyngeal cancer cells in dose-dependant. (p < 0.05). H31 was tolerable toxic to normal cell line (HaKaT cell) at high concentration. H31 induced tumor cell necrosis and partially apoptosis in test of DNA fragmentation analysis and FACScan with Annexin V-FITC. H31 increased expression of cytochrome C, phosphorated c-Jun in Western blot and induced phosphorated P53, tumor suppressor gene. In vivo test of neurotoxicity, H31 was not toxic to neuromast and auditory hair cell contrary to the cisplatin. Conclusion: This study suggests the potential of using H31 as chemopreventative or therapeutic agents in head and neck squamous cell carcinoma . Green tea extracts-induced expression of NAG-1 is associated with growth inhibition and proapoptotic activity in Head & Neck cancer cell lines. International Congress on Cell Biology(Seoul, Korea, Oct 7-10,2008) NSAID activated gene (NAG-1) was pro-apoptotic and antitumorigenic protein. In this report, we have investigated signaling pathways affected by EGCG and propose herein an overview of how EGCG induces apoptosis in HNSCC. HNSCC lines after treatment of green tea extracts were incubated with varying concentrations. Cell viability was measured by MTT assay. TUNEL & Annexin V-PI staining were performed to detect whether the death of EGCG-induced in cells was caused by apoptosis. We performed transfection of NAG-1 cDNA and siRNA into cells and studied whether ectopic expression of NAG-1 was or not. EGCG decreased the viability of cells in a dosedependent manner. EGCG increased TUNEL-positive cells and Annexin V positive cells. NAG-1 mRNA level was increased dose dependent on EGCG concentration, and HNSCC transfected with NAG-1 cDNA did not survive during expansion and significantly induced apoptosis. In contrast, when NAG-1 knockdown, apoptosis was reduced. NAG-1 as an antitumorigenic activity regulated by EGCG may result in the development of new products for the treatment of HNSCC. Epicatechin protects auditory cells against radiation-induced death International Congress on Cell Biology(Seoul, Korea, Oct 7-10,2008) Radiation is widely used to treat various cancers but promotes ototoxicity at higher doses. In this study, the effect of epicatechin(EC) on radiation-induced hair cell death was investigated in a cochlear organ of Corti-derived cell line, HEI-OC1, and in vivo in zebrafish. Radiation promoted apoptosis and altered mitochondrial membrane potential in HEI-OC1 cells. EC inhibited cisplatininduced apoptosis and intracellular reactive oxygen species (ROS) generation. Labeling of zebrafish lateral line hair cells by the fluorescent dye YO-PR01 was lost and distorted upon exposure to radiation, and EC protected against this radiation-induced loss of labeling in a dosedependent manner. Scanning and transmission electron micrographs showed that treatment with EC protected against radiation-induced loss of kinocilium and stereocilia in zebrafish neuromasts. These results suggest that EC prevents radiation-induced ototoxicity by blocking ROS generation and by preventing changes in mitochondrial membrane potential. |
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| 2009 | ||||
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Isolated congenital ossicular anomaly Seven Departments Joint Meeting of Otolaryngology (Osaka, Japan: Mar 27-28, 2009) Background: A non-progressive and conductive hearing loss in the range of 40 to 60dB with normal tympanic membrane which has no history of trauma or infection is highly suggestive of a congenital ossicular malformation. Stapes anomaly is the most common among the ossicular anomalies, and they are clinically important because hearing loss can be corrected by appropriate procedure. The purpose of this study is to describe patterns of the ossicular anomaly encountered in patients who have a normal eardrum, and to analyze its surgical result with special reference to its patterns. Study design: I experienced 78 cases(94 ears) of congenital ossicular anomaly which were confirmed through the explotympanotomy for the last 20 years. The preoperative and postoperative audiologic findings, operative findings and temporal bone CT findings were analyzed. Results: There were 20 anomalous patterns of ossicular anomaly among which stapes footplate fixation was the most common anomaly. I classified congenital ossicular anomaly into 5 types according to the status of the stapes footplate. Stapes footplate fixation was the most common type which was usually bilateral, while anomalies associated with incus and malleus were usually unilateral. I could get hearing improvement in 72.3% of my cases after surgery. Conclusions: There were a great diversity of patterns of ossicular anomaly, which were detected without a certain rule of pattern and big variety of those patterns can be detected again in the future. The success of surgical treatment of congenital ossicular anomaly might depend on the status of the stapes footplate. Clinical analysis of horizontal canal Benign Paroxysmal Positional Vertigo according to the presence or absence of spontaneous nystagmus Seven Departments Joint Meeting of Otolaryngology (Osaka, Japan: Mar 27-28, 2009) Objective: Benign Paroxysmal Positional Vertigo (BPPV) is a common form of vertigo caused by dislodged otoconia making its way from the utricle mainly into the posterior semicircular canal. In 5% to 22% of cases, the otoconia will be displaced into the horizontal canal, or more rarely, the anterior canal. Recently, there are some reports on horizontal canal BPPV (h-BPPV) who showed spontaneous nystagmus (SN). The aim of this study is to evaluate the incidence of SN in h-BPPV and to compare patients’ response to physical treatment and outcome of patients with h-BPPV with SN with those with h-BPPV without BPPV. Material and Methods: A prospectively designed study was carried out at Department of Otolaryngology, Ajou University Hospital, Suwon, Korea. Computer analysis of ENG recordings was routinely performed. Video-oculographic recording included spontaneous nystagmus in the primary position of the eye and positional testing. Results: Sixteen patients (24.1%) of 66 showed SN. Fifty percent of patients with h-BPPV with SN required repeated physical treatments in comparison to 18% of patients with h-BPPV without SN. Conclusions: It appears that h-BPPV with SN is more difficult to treat than h-BPPV without SN. Significance of osteoporosis in facial bone density using the computerized tomography scan Seven Departments Joint Meeting of Otolaryngology (Osaka, Japan: Mar 27-28, 2009) Objective: To evaluate and compare the variations of bone density in mid-facial bone measured by QCT(Quantitative Computerized Tomography) scan between osteoporosis group and control group. We also tried to find out the region which was closely associated with facial bone fracture due to trauma and iatrogenic osteotomy. Materials and Methods: Eighty two patients who underwent both Osteomeatal unit(OMU) CT scans and Dual-Energy X-ray Absorptiometries (DEXA) at Ajou Univ. Medical Center were included in this retrospective study. Thirty- three patients (25 female, 8 male, mean age 57.66) were in osteoporosis group, forty-nine patients (39 female, 10 male, mean age 56.63) were in control group. Seven skeletal regions were chosen for each patient and each side ;Group A(Ortial floor(OF), Nasal bone(NB)), Group B(Zygomaticomaxillary suture(ZMS), Zygomatic arch(ZA), Zygomaticofrontal suture (ZFS)), Group C(Anterior wall of maxillary antrum(AM), Maxillary process(MP)). As a result, 1148 ROI(Region of Interest) region were considered for this study. The QCT scan were reviewed with the PACS(Picture Archiving and Communication System: Piview, INFINITT Technology Co., Ltd., Seoul, Korea). Pixel intensity was analyzed by indicating the mouse in the ROI and HU(Housefield Unit) were measured. The facial bone mineral density of mid-facial bone region was compared between osteoporosis group and control group. Result: The significant difference in the mean bone density of mid-facial bone had been established between the osteoporosis group and control group (P < 0.01) except only ZMS (P > 0.05). In both groups, the facial bone mineral density of Group A was the smallest and the group C was the largest group. (P < 0.01). Conclusions: We could see the difference of the facial bone mineral density between the osteoporosis and the control group using the QCT scan. Therefore, osteoporosis patients can be traumatized easily in the facial region. Also, delicate care should be provided during osteotomy procedure in these patients. The change of bone conduction threshold in patients with chronic otitis media The 6th Extraordinary International Symposium on Recent Advances in Otitis Media (Seoul, Korea: May 6-10, 2009) Introduction: Chronic otitis media (COM) is generally associated with some degree of hearing loss, which is often the patient’s chief complaint. While the conductive loss can be minimized through surgery, sensorineural hearing loss (SNHL) cannot improve permanently, attenuated only through use of a hearing aid. The objective of this study was to evaluate whether COM can cause worsening of bone conduction (BC) thresholds by comparing affected ears with their normal contralateral counterparts. And it was to clarify whether surgeries could improve bone conduction thresholds in COM patients by comparing the BC threshold of affected ears between preoperatively and postoperatively. Materials and Methods: One hundred and ninety-nine patients from the COM outpatient clinic of Ajou Medical Center were evaluated. Inclusion criteria were: (1) normal tympanic membrane in the contralateral ear; (2) the presence of chronic, unilateral otitis media, defined as inflammation of the middle ear cavity lasting more than 3 months, with tympanic perforation, without associated cholesteatomas; (3) a contralateral audiometry with BC threshold < 30 dB at 0.5, 1, 2, and 4kHz frequencies with no air-bone gap; (4) no specific cause of SNHL such as ototoxicity due to medication, noise exposure, or labyrinthitis; (5) first otologic surgery due to unilateral COM. We analyzed the information of the patients including sex, age, past medical history, duration of symptoms, pre-operative Pure Tone Audiometry (PTA), the name of surgery, and post-operative 2 or 3 months follow-up PTA. Results: It showed that the significant correlation between age and pre-op BC thresholds of the affected ear. In other words, the older, the worse. But, there was no significant correlation between the duration of COM and pre-op BC threshold. Thus, we defined the interaural BC gap; that is the numerical difference between pre-operative BC of the affected ear and BC of the normal ear. There was significant correlation between age and interaural BC gap. The older, the larger. And it also showed that significant correlation between the duration of COM and the interaural BC gap at 0.5 & 1 kHz. The longer the duration was, the larger the interaural BC gap was. As well, there was significant change of BC threshold between preoperative and post-operative hearing level at 0.5, 1, and 2k Hz. But, it showed no significant differences in recovery of BC threshold between tympanoplasty and tympanomastoidectomy. Conclusions: The interaural BC gap is more important to evaluate the change of BC threshold in patients with COM rather than a use of absolute BC threshold. The interaural BC gap depends on patients’ preoperative age and partially on the duration of COM. BC threshold is significantly recovered after surgeries, tympanoplasty or tympanomastoidectomy. These results suggest that BC threshold seems to be caused by both the change of sound conduction and inflammatory mediators. Management of congenital mesotympanic cholesteatoma in children The 19th World Congress of Otorhinolaryngology-Head and Neck Surgery (São Paulo, Brazil: Jun 3, 2009) There is an increasing awareness of congenital cholesteatomas in recent decades. The location of the congenital cholesteatoma, when possible initially, can be classified in relation to the four quadrant of the eardrum. ross-pathologically, there are two types of congenital cholesteatoma: a closed keratotic cyst and an open matrix. Patients with open-type congenital cholesteatoma may have a different clinical presentation from the classical description of congenital cholesteatoma. The staging system of the congenital cholesteatoma which influences its surgical approaches shows its extension according to its involvement and ossicular erosion. This study aimed to analyze clinical characteristics of cases with congenital cholesteatoma in the middle ear under the age of 10, and to facilitate better understanding of its management. We reviewed retrospectively 91 patients who were diagnosed as congenital middle ear cholesteatoma under its definite criteria in Ajou University Hospital for the last 14 years (1994-2008). This study was done by analyzing the patients’ history, drum finding, temporal bone CT finding, operative finding and pathologic finding. In this study, the open-type congenital cholesteatoma which was less common and usually originated from posterosuperior quadrant of the mesotympanum showed higher degree of hearing loss and more frequent unusual presentation, and detected at an older age than the closed-type congenital cholesteatoma. 31 cases (34.1%) with congenital cholesteatoma were associated with OME. 77 cases (84.6%) with congenital cholesteatoma were confined to the mesotympanum, of which surgery were done mostly through the transcanal approach. The recidivism was detected in 10 cases (11.0%). In conclusion, management of mesotympanic congenital cholesteatoma in children may be done as soon as possible when diagnosed. The treatment algorithm of congenital cholesteatoma according to its stage requires further discussion for the better result. Rat model for chronic tympanic membrane perforation and the efficiency of chitosan patch scaffold for treatment 27th Politzer Society Meeting (London, UK: Sep 3-5, 2009) Chronic tympanic membrane perforation (CTMP) is a representative otologic disease that requires surgical procedures. However, there have been no good alternative managements which can easily be applied at outpatient clinics and also no ideal animal models for the study of CTMP. Therefore, we devised rat models for CTMP and assessed the efficiency of chitosan patch scaffolds (CPS) which we had previously developed. We applied the following eight methods to 85 Sprague-Dawley rats to make CTMP which could remain for at least four weeks; I) simple perforation, II) mitomycin C (MC) for 10 min in the perforation areas, III) MC for 10 min and then saline gelfoam for 1 week, IV) MC for 10 min and dexamethasone gelfoam for 1 week, V) MC gelfoam for 1 week, VI) dexamethasone gelfoam for 1 week, VII) making perforation with a heated pick, and VIII) local application of dexamethasone gelfoam for 1 week after making perforations with heated micropicks. Among these methods, the method VIII showed 100% successes rate for maintenance of perforations over 4 weeks, followed by V (75%), IV (35.7%), and III (33.3%), whereas the methods I, II, VI, and VII showed 0%. Next, we assessed the healing efficiency of CPS using the CTMP models by comparing with paper patches and none management. In the method VIII models, there was no perforation healed with any patches during more than 9 weeks. In the animal models prepared with the method V, the CPS-applied rats showed 70% of healing rate which was better than 40% in rats with paper patches or none managements. These results indicate that animal models with CTMP could be prepared with local application of MC for 1 week, and that CPS might be potentially an ideal material that could affordably be used in office-based settings for the regeneration of CTMP. |
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| 2010 | ||||
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The differential vulnerability across cochlear turns in gentamicin-induced hair cell damage is correlated with the differential uptake of gentamicin The 33rd Annual Midwinter Research Meeting in Association for Research in Otolaryngology (Anaheim, CA, USA: Feb 6-10, 2010) Purposes: Basal turn hair cells (HCs) in the organ of Corti (oC) is most vulnerable to gentamicin(GM) followed by middle turns and apical turns. Moreover, the differential sensitivity of HCs appears to be closely related to differences in highly reactive oxygen species (hROS) formation (Choung YH, 2009). The purpose of this study is to evaluate whether the differential vulnerability across cochlear turns in GM-induced HC damage is correlated with the differential uptake of GM. Materials and Methods: Explants of basal, middle or apical turn in organ of Cortis (oCs) from neonatal (p3) rats were cultured and exposed to GM(50uM, 35uM) for 48h. The uptake of GM was evaluated by immunohistochemistry using anti-GM antibody. These explants were colabeled with MyoVIIa (hair cell staining) and DAPI (nucleus staining) for detection HC loss across cochlear turns. The intensities of GM fluorescence expressed in HCs were compared in each turns and rows and also analyzed comparing with the loss of hair cells. Results: Basal turn HCs showed more intense GM fluorescence than middle turn HCs and very little GM uptake was observed in the apical turn when OC explants were exposed to GM 35uM for 48h. The differential uptake of GM across turns was not definite in the OC explants exposed to GM 50uM. The intensity of GM fluorescence was strongest in the 1st row of outer HCs, followed by 2nd and 3rd rows. The expression of GM was correlated with the damage of HCs in all cochlear turns and outer HC rows showing differential vulnerability of HCs. Interestingly, GM uptake was not expressed in HCs with weak staining of MyoVIIa and GM uptake was well correlated with the intensity of MyoVIIa expression. Conclusions: The differential vulnerability across cochlear turns in GM-induced hair cell damage is correlated with the differential uptake of GM and GM uptake may be dependent on MyoVIIa expression in HCs. |
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