Vestibular Hair Cell Regeneration in Guinea Pig after Gentamicin Damage / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: The recovery of the vestibular sensory epithelia of guinea pigs after gentamicin (GM) induced hair cell injury was assessed both quantitatively and qualitatively with a functional study of the vestibular system using animal rotatory chair. MATERIALS AND METHOD: Evaluations were made via calculating the number of utricle cells bearing hair bundles using scanning electron microscopy (SEM). The number of ampullar hair cells and supporting cells were calculated by toluidine blue staining. Animal rotatory chair test was performed for the evaluation of functional recovery of vestibular system after gentamicin damage in guinea pigs. RESULTS: The initial loss of hair cells in utricle and ampulla were followed by the recovery of hair cell number. The quantitative analyses indicated that the lost hair cells were replaced or regenerated after the end of GM administration, or at 3 months. SEM revealed the morphological recovery of the damaged hair cells and new hair cell regeneration in utricle. In animal rotatory chair test, the gain in slow harmonic acceleration were decreased immediate after GM application, and the gain increased over 3 months. The value of bias off the vertical axis rotation also decreased immediatly after the GM application, and the decreased value of bias were partially recovered. CONCLUSION: We find guinea pig vestibular hair cell regeneration after gentamicin damage with morphologic and functional study.

iNOS Expression in Inner Ears of Guinea Pigs Injured by PAF / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Platelet-activating factor (PAF) in middle ear effusion is thought to induce hearing loss. The purpose of this study is to determine the effects of PAF placed on round window membrane (RWM) on hearing and cochlear hair cells in guinea pigs, and we also wanted to investigate the role of nitric oxide (NO) in the mechanism of PAF-induced hearing loss by comparing its immunoreactivity to iNOS between the control group and PAF application group. MATERIALS AND METHOD: Guinea pigs were divided into 2 groups: PBS, PAF. The PBS group received phosphate buffered saline (PBS) and the PAF groups received 10, 20, and 40 mug/ml of PAF soaked in gelfoam placed on the RWM. The following three tests were performed on each animal group: hearing was tested with an auditory brainstem response (ABR) test through 24 hours. At the end of 24 hours, cochlear hair cells were examined by scanning electron microscopy (SEM) and immunohistochemistry was carried out on the cochlea to test the expression of inducible nitric oxide (iNOS). RESULTS: The PAF group developed significant elevation of ABR threshold and cochlear hair cell damage in SEM compared with the PBS control group. Strong expression of iNOS on cochlea was observed in the PAF group and lighter expression was seen in PBS group. CONCLUSION: This study demonstrated that PAF placed on the RWM induced hearing loss, and cochlear hair cell damage, and strong iNOS expression in the cochlea. These findings suggest that the PAF-induced hearing loss caused by cochlear hair cell damage may have been mediated by NO. PAF-antagonists and NOS inhibitor may have future therapeutic implications in preventing sensorineural hearing loss associated with chronic otitis media.

Evaluation and Prevention of Gentamicin-induced Vestibulotoxicity in Rabbits Using Off-Vertical Axis Rotation / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: The purposes of this study was to investigate the characteristics of gentamicin-induced vestibulotoxicity of s otolith organs by assessing the results of earth vertical and the off-vertical axis rotation tests with a morphologic study. MATERIALS AND METHODS: Rabbits were grouped into two groups, ototoxic and ototoxic prevention group. Vestibulotoxicity was induced by injecting gentamicin (GM) into the peritoneum. Prevention of the vestibulotoxicity was studied by injecting NMDA receptor inhibitors (MK-801), iron chelating agents (deferoxamine) peritonially, and osmotic pumps filled with neurotrophic factors (GDNF, BDNF), respectively. The animal rotation system was designed to rotate the animal sinusoidally or in velocity step (constant velocity) rotation. Off-vertical rotation was applied to evaluate the otolithic function. Scanning electron microscopy were examined for the structural changes of the otolithic organs. RESULTS AND CONCLUSIONS: GM-induced vestibulotoxicity was confirmed by gain decreasing in the earth vertical SHA rotation test and bias decreasing in the off-vertical rotation test. However, changes in modulation was not definite. Bilateral prevention of GM-induced vestibulotoxicity was confirmed by systemic injection of deferoxamine and MK-801, and characteristics of unilateral prevention was confirmed by local application of the neurotrophic factors using osmotic pumps. In the SEM study, the GM-induced hair cell damages of the vestibule were identified, which was prevented by the preventive drugs. The reduction of bias value without change of modulation was comparable with the reduction of gain in the earth vertical axis rotation after GM-induced vestibulotoxicity.

Audiologic Follow-up Evaluation of Patients with Hyperbilirubinemic Sensorineural Hearing Loss / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: In neonates with hyperbilirubinemic sensorineural hearing loss, the lesion site is supposed to be confined to the retrocochlea. The purpose of this study is to investigate the changes of hearing level and the progression of the lesion site involving cochlear area after a lapse of time in the patients with hyperbilirubinemic sensorineural hearing loss. MATERIALS AND METHOD: ABR, TEOAE and IA tests were performed on 11 neonates with severe hyperbilirubinemia with exchange transfusion in the period of neonates. After more than 4 years, follow-up ABR, TEOAE, and IA tests were carried out in the same 11 children. RESULTS: In the initial ABR test, 4 neonates showed abnormal or no response and the other 7 neonates demonstrated normal response. All 11 neonates passed TEOAE and showed A type in IA In the follow-up tests after more than 4 years, 7 children who had shown normal ABR, TEOAE and IA test results as neonates showed normal ABR, TEOAE, and IA. In 4 children who had abnormal ABR results, showed decreased ABR thresholds. In TEOAE, 3 children showed bilateral failures and 1 child showed unilateral failure. CONCLUSIONS: The results of this study suggests that the sites of lesion in hearing loss caused by hyperbilirubinemia were at the retrocochlear location as neonates. But the lesions may affect the cochlear lesions after a lapse of time. And some residual hearing may be preserved.

The Ototoxicity of Cisplatin is Mediated by NO: A Study using L-NAME and MK-801 in Guinea pigs / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Nitric oxide has been suggested to play an important role in the pathogenesis of cisplatin ototoxicity. L-NAME (NG-Nitroarginine Methyl Ester) is an inhibitor of nitric oxide synthase. MK-801 (Dizocilpine Maleate) is a NMDA receptor antagonist. To evaluate a role of nitric oxide in cisplatin ototoxicity, we investigated whether L-NAME and MK-801 can block the cisplatin ototoxicity in guinea pigs. MATERIALS AND METHOD: In the Group 1, normal saline was injected intraperitoneally as a control group. Group 2, 3, 4, and 5 were injected intraperitoneally as described in the following: Group 2, cisplatin only; Group 3, L-NAME+isplatin; Group 4, MK-801+cisplatin; Group 5, L-NAME+K-801+cisplatin. Using an auditory brainstem response, hearing threshold was tested before cisplatin administration and 5 days after cisplatin injection in each group. The morphological changes of the cochlea were observed by scanning electron microscopy. RESULTS: In the Group 2, a significant hearing loss was observed comparing to Group 1. In contrast , Group 3, 4, and 5 did not demonstrate any significant hearing loss compared to Group 1. In the scanning electron microscopy, the Group 2 showed distorsion and loss of stereocilia of the hair cells. However, the Group 1, 3, 4, and 5 demonstrated well preserved cochlear hair cell morphology. CONCLUSION: Hearing loss induced by ototoxicity of cisplatin was prevented by L-NAME and MK-801. This study suggests that NO may mediate cisplatin ototoxicity.

Clinical Analysis of Bilateral Vestibulopathy

From retrospective review of medical charts of patients diagnosed as bilateral vestibulopathy during the past seven years, this study investigated incidence, etiologies, symptoms, vestibular function test findings; electronystagmography (ENG) studies, rotatory chair testing, and posturography, and post-vestibular rehabilitation (VRT) follow-up results. we have an incidence of 1.2% of all the 3423 patients who have undergone vestibular function test. Ototoxicity was the first known etiology and we had a lot of patients of idiopathic bilateral vestibulopathy. Most patients in our study had experiences of sudden onset vertigo rather than slowly progressive symptoms. The most frequently complained symptoms were dysequilibrium and oscillopsia. Post-VRT courses were better in patients whose initial gain of vestibulo-ocular reflex(VOR) was high or ascending type.

The protective effect of nitirc oxide synthase inhibitor on hearing loss induced by TNF-alpha and IL-1beta injection into CSF in guinea pigs / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: One of the most serious complications of bacterial meningitis, particularly in childhood, is sensorineural hearing loss; yet the mechanisms of this hearing loss are not clearly understood. It is also known that the levels of TNF-alpha, IL-1beta in CSF are significantly elevated in bacterial meningitis patients. This study is designed to evaluate the role of nitric oxide (NO) in the ototoxic effect of TNF-alpha and IL-1beta injected into CSF of guinea pigs. MATERIALS AND METHODS: Twenty-six guinea pigs (52 ears) were randomly assigned into six groups consisting of a control group, a NG-nitro-L-arginine methyl ester (L-NAME) group, a TNF-alpha group, a TNF-alpha plus L-NAME group, a IL-1beta group and a IL-1beta plus L-NAME group. The thresh shifts of the auditory brain stem response (ABR) were measured before, 6 and 24 hours after the administration of cytokines. TNF-alpha and IL-1beta were directly injected into the cisterna magna in a dosage of 0.1 microgram in 10 microgram/ microliter concentration. L-NAME, a NO synthase (NOS) inhibitor, was injected intraperitoneally 30 minutes prior to the administration of cytokines. Scanning electron microscopy was used to find the morphological damage of the hair cells. RESULTS: In TNF-alpha group, the ABR thresh shift after injection of 6 and 24 hours was 19.2 +/- 10.2 dB, 18.3 +/- 10.3 dB, in the TNF-alpha plus L-NAME group, 3.3 +/- 2.6 dB, 8.3 +/- 4.1 dB, in the IL-1beta group, 6.9 +/- 4.6 dB, 11.25 +/- 8.3 dB, and in the IL-1beta plus L-NAME group, 1.7 +/- 2.7 dB, 1.3 +/- 2.5 dB, respectively. There was damage in the 2nd, 3rd row of the outer hair cells in the TNF-alpha and IL-1beta group. CONCLUSION: This study suggests that the sensorineural hearing loss associated with bacterial meningitis is caused in part by the actions of proinflammatory cytokines such as TNF-alpha, IL-1beta and that these are mediated by NO.

DNA-mediated Immunization Methods with the HCMV gB for the Induction of Neutralizing Antibodies to HCMV in BALB/c Mice

No abstract available.

Culture of Tonsillar Follicular Dendritic Cells / 대한면역학회지

Presentation of antigen in a suitable form to lymphocytes is prerequsite for the initiation of primary immune response. Dendritic cells (DC) provide an effective pathway for presenting antigens to lymphocytes in situ. The aim of this study was to establish a dendritic cell-line from human tonsils and to investigate the changes in surface phenotype during culture. Immunohistochemical studies using various surface markers indicated that cultured DC were follicular dendritic cells (FDC) from human tonsils. Cultured DC showed typical dendritic morphology at early stage of culture. Their shape changed into fibroblast-like cells over culture time. Surface phenotype study suggested that cultured DC were distinct from human fibroblast. Antigenic pattern of FDC was changed during culture; I-ILA-DR antigens decreased and HJ2 antigens increased with aging of culture. Functional characteristics of human tosillar FDC will be investigated in the future.

The Relationship between Ciliary Beat Frequency and Maxillary Sinus Mucosal Hypertrophy on Computed Tomography in Patients with Chronic Sinusitis / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: This study was designed to investigate the relationship between the sinus mucosal hypertrophy and ciliary beat frequency (CBF) in patients with chronic sinusitis in vitro. MATERIALS AND METHODS: In 14 patients with chronic sinusitis, mucosal samples were obtained from the superior, inferior, and lateral walls of the maxillary sinus. Using a video-computerized analysis technique, we measured two parameters for ciliary activity at five different sites selected randomly from each sample=the ciliated area (%) showing CBF equal to or higher than 10 Hz (A10) and the weighted frequency (Fw). Mucosal hypertrophy of the maxillary sinus was calculated using a computer program on CT scans. RESULTS: A(>or=10) and Fw were 91% and 11.3 Hz in control group, respectively, whereas they were 47% and 9.1 Hz in chronic sinusitis group, respectively (p=0.03). There was a significant inverse correlation between A(>or=10) or Fw and mucosal hypertrophy of the maxillary sinus (p=0.001). CONCLUSION: The results of this study suggest that the severity of mucosal hypertrophy on CT scan may correlate with the ciliary activity.

Peservation of Facial Nerve Function after Acoustic Neuroma Surgery / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Facial nerve paralysis is a visible complication following acoustic neuroma surgery. The pro-gnostic factors which predict postoperative facial nerve function after acoustic neuroma surgery were investigated. MATERIALS AND METHODS:Fifty one patients with acoustic neuroma operated with neurotological approaches from March, 1987 to May, 1997 at Seoul national university hospital were studied by retrospective medical record review. Patient groups were divided according to surgical approach which were selected on the basis of tumor location and size as well as the need for hearing preservation. They were also divided according to the extent of tumor, preoperative facial nerve function, and tumor size. Under the House-Brackmann grading system, preservation of facial nerve function for each of the groups was analyzed before the operation, immediately after the operation (7th day), and at the time of last follow up (>12 month). The mean age of patients was 49.3 years, ranging from 29 to 72 years. Spearman Correlation analysis was used for statistical evaluation. RESULTS: The extent of tumor or different surgical approaches of tumor removal, such as translabyrinthine, transotic, middle fossa, and the combined approach, did not influence on facial nerve preservation. Pre-operative and immediate postoperative facial nerve functions as well as tumor size were important prognostic factors in the long term facial nerve function. As the size of tumor increased, the long term postoperative facial nerve function became poor. CONCLUSION: Early diagnosis and surgery are required for small size tumors in order to have good facial nerve function following acoustic neuroma surgery.

Familial Hearing Loss Associated with mtDNA A1555G Mutation in Korea: 1 Pedigree / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Familial aminoglycoside-induced deafness has been described in a number of Chinese and Japanese pedigrees. Recently, the familial aminoglycoside-induced ototoxicity is proved to be associated with a mutation in mitochondrial (mt) 12S ribosomal RNA (rRNA) gene at nucleotide position 1555 in some families. In this study, we analyzed mt 12S rRNA gene to find out this particular mutation in Korean pedigrees who had a family history of hearing loss. MATERIALS AND METHODS: Peripherial blood was obtained from 91 individuals of 30 families, and total genomic DNA (gDNA) was extracted. A fragment of DNA including a part of mt 12S rRNA gene was amplified by polymerase chain reaction (PCR). The PCR products were analyzed by restriction digestion with Bsm A1 and DNA sequencing. RESULTS: We found one family of mtDNA A1555G. Six family members had mutant genotype and three of them showed severe sensorineural hearing loss or deafness. The mutation was homoplasmic in all affected family members, and the genotype revealed maternal transmission. CONCLUSION: We found the first case of familial hearing loss genetically proved to be associated with the mt 12S rRNA gene mutation, in Korea. Because it is possible that an individual with this mutation shows a progressive sensorineural hearing loss, a screening of mtDNA A1555G mutation for the familial members who have a maternal inheritant hearing loss might be necessary.

Expression and Role of Adhesion Molecules in the Nasal Mucosa of the Rat with Experimentally Induced Allergic Rhinitis / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Airway allergic reactions are induced by infiltrating inflammatory cells into the human airway tissues through interactions between vascular endothelial cells, inflammatory mediators and adhesion molecules. Accordingly, it is important to study the role of adhesion molecules for the evaluation of pathophysiology of allergy. The aim of this study is to investigate the effect of monoclonal antibodies against intercellular adhesion molecule-1 (ICAM-1) and leukocyte function associated molecule-1 (LFA-1) on the pathophysiology of allergy in ovalbumin-sensitized rats. MATERIALS AND METHODS: We developed an allergy model in rat using the intraperitoneal injection and intranasal nebulization of ovalbumine solution. We evaluated in vivo effects of ICAM-1 and LFA-1 monoclonal antibodies on the expression of ICAM-1 and LFA-1 in ovalbumin sensitized rats. RESULTS: Nasal symptoms after allergen challenge were significantly suppressed and the number of eosinophil in nasal mucosa were significantly inhibited by the treatment of adhesion molecule antibodies. Anti-ICAM-1 and anti-LFA-1 monoclonal antibodies suppressed the expression of ICAM-1 and LFA-1 in nasal mucosa of ovalbumin-sensitized rats. CONCLUSION: It is suggested that allergy can be managed by a useful treatment method using adhesion molecule antibody.

Ciliary Beat Frequency of Middle Ear, Eustachian Tube and Other Upper Respiratory Tract in Mice / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: The aim of this study is to analyze ciliary beat frequency (CBF)and ciliary morphology of the middle ear bulla and the upper respiratory tract in mice. MATERIALS AND METHODS: Fifteen mice with 37-42 gram weight were dissected and specimens were taken from the middle ear bulla, the eustachian tube, the inferior turbinate, the nasopharynx, and the upper trachea. The CBF of each specimen was measured using a video-computerized analysis system and the morphology of cilia was also studied using scanning electron microscopy (SEM). RESULTS: The measured CBF ranged from 9.38 Hz to 13.59 Hz, and there were no significant differences in the CBF values among the middle ear bulla, the eustachian tube, the inferior turbinate and the nasopharynx, except for the upper trachea. The mean CBF value of the upper trachea was 11.6 Hz, which was significantly lower than those of other parts. SEM showed that the cilia of the upper tracheal region were shorter than those of other parts. CONCLUSION: The CBF value of the middle ear bulla is similar to those of other parts in the upper respiratory tract except for the upper trachea. In the upper trachea, the CBF is lower and ciliary lenghth of epithelium is shorter than those of other parts.

Voice Analysis in Reinke's Edema / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Reinke's edema is defined as swelling confined to the space underneath the epithelial layer known as Reinke's space. Patients suffering from Reinke's edema are known to have abnormally low fundamental frequency and high subglottic pressure. We compared the preoperative and postoperative voice results of Reinke's edema to evaluate quantitative changes of vocal function. MATERIALS AND METHODS: The voice analyses of 15 patients, who were diagnosed with Reinke's edema from 1997 January to 1998 September in Seoul National University Hospital, and 15 normal controls were undertaken with Multi-dimensional voice program (MDVP) and Aerophone II of Kay system. Eight preoperative patients, 13 postoperative patients, and 6 preoperative and postoperative patients were analyzed with respect to fundamental frequency (F0), pitch perturbation quotient (PPQ), amplitude perturbation quotient (APQ), noise-to-harmonic ratio (NHR), subglottic pressure (Psg), mean vocal efficiency, mean flow rate (MFR), maximum phonation time (MPT), and contact quotient (CQ). Using videostrobokymography, vibratory patterns of vocal folds were analyzed. RESULTS: The fundamental frequency was lower than the normal preoperative and postoperative values. The PPQ, APQ, and NHR were decreased to the normal value after operation. The subglottic pressure, although elevated preoperatively and decreased postoperatively, remained high. The mean vocal efficiency was increased to average value of normal controls after operation. The MFR, MPT, and CQ were not correlated with the course of Reinke's edema. The vocal folds vibration returned to regular pattern after operation on videostrobokymography. CONCLUSION: The fundamental frequency and subglottic pressure are not normalized after operation, and the PPQ, APQ, and NHR are good parameters of postoperative voice results. The voice therapy might help to correct the vocal habit of voice abuse and prevent recurrence after operation.