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Background and Objectives This work investigates the clinical characteristics of benign paroxysmal positional vertigo (BPPV) according to etiology by comparing idiopathic BPPV (iBPPV), BPPV occurring after head trauma (tBPPV) and BPPV associated with idiopathic sudden sensory neural hearing loss (sBPPV).Subjects and Method A total of 869 patients who were diagnosed and treated for BPPV were reviewed retrospectively. Patients were divided into three groups according to the probable etiology of BPPV: iBPPV vs. tBPPV vs. sBPPV. We investigated and compared demographics, the affected sides and canals, the number of canalith repositioning procedure (CRP) performed to achieve successful reposition, canal conversion and recurrence among the three groups. Among the three groups, BPPV patients who performed caloric test and/or video head impulse test (vHIT) were additionally evaluated and compared.Results The iBPPV group (n=787) had greater female preponderance (72%, 567/787) than the tBPPV (n=51) and sBPPV groups (n=31, p

Background/Aim: This study aimed to investigate the process of homeostatic restoration in the tracheal mucosa (TM) after thyroid surgery. Materials and Methods: Fifty-four rats were divided into normal controls (NC) and three experimental groups: (i) flap elevation (FE), (ii) thyroid exposure (TE), and (iii) thyroid isthmusectomy (TI). Expression of mRNA and proteins of key factors regulating homeostasis were evaluated in the TM obtained 3, 7, and 21 days after thyroid surgery. Results: Increased mRNA expression of transforming growth factor-β1 (TGF-β1), hypoxia-inducible factor-1α (HIF-1α), and matrix metalloproteinase-9 (MMP-9) were observed 21 days after thyroid surgery in all experimental groups compared to that of NC group. Conclusion: Thyroid surgery leads to an actual increase of TGF-β1, HIF-1α, and MMP-9 expression in the TM. This increased expression of key regulators of homeostatic restoration in the TM lasts for a considerable period of time after surgery, especially if the extent of surgery increased.

Objectives. Human amniotic membrane extract (AME) is known to contain numerous bioactive factors and anti-inflammatory substances. However, the anti-inflammatory effects of AME on the middle ear (ME) mucosa are unclear. This study assessed the effects of AME on the growth of the ME mucosa in response to bacterially-induced otitis media (OM).Methods. OM was induced by inoculating nontypeable Haemophilus influenzae (NTHi) into the ME cavity of rats. ME mucosal explants were cultured in AME concentrations of 0, 5, 10, or 50 μg/mL. The area of explant outgrowth was measured in culture and analyzed at 1, 3, 5, and 7 days after explantation. The expression of Ki-67, mucin 5AC (MUC5AC), tumor necrosis factor-α (TNF-α), and interleukin-10 (IL-10) in the explants was also evaluated using quantitative polymerase chain reaction (PCR) and immunocytochemistry (ICC).Results. The NTHi-induced ME mucosa growth increased gradually over the 7-day culture period in all explants at different AME concentrations. There was a trend for mucosal growth inhibition at higher concentrations of AME, although the growth was not significantly different among the groups until day 5. The ME mucosal explants treated with the 50 μg/mL concentration of AME showed significantly suppressed growth on postexplantation day 7 compared with other explants on the same day. PCR and ICC staining revealed that the expression of Ki-67, MUC5AC, TNF-α, and IL-10 further decreased in the explants with higher concentrations of AME than in those with lower concentrations of AME.Conclusion. Our results showed that higher concentrations of AME reduced the mucosal proliferative response in bacterial OM in rats. These findings provide evidence that AME has an influence on the inflammatory and proliferative responses to NTHi infection in ME mucosa.

Objectives. The objectives of this study were to identify the clinical features and chest computed tomography (CT) findings of coronavirus disease 2019 (COVID-19) patients and to compare the characteristics of patients diagnosed in Wuhan and in other areas of China by integrating the findings reported in previous studies.Methods. We conducted a proportion meta-analysis to integrate the results of previous studies identified in online databases, and subsequently compared the overlapping of 95% confidence intervals (CIs) between locations of diagnosis. The heterogeneity of the results of the included studies was also demonstrated.Results. Nine studies with level IV evidence were considered to be eligible for the meta-analysis, and a comparative analysis was only possible between patients diagnosed in Wuhan and outside of Wuhan in China. Fever (84.8%; 95% CI, 78.5% to 90.1%) was identified as the most common clinical manifestation in all COVID-19 patients, and signs of respiratory infection were also frequently present in these patients. When comparing the clinical features according to the location of diagnosis, fever and dyspnea were less frequent in patients diagnosed outside of Wuhan (fever: 78.1%; 95% CI, 73.2% to 82.7%; dyspnea: 3.80%; 95% CI, 0.13% to 12.22%) than in patients diagnosed in Wuhan (fever: 91.7%; 95% CI, 88.0% to 94.8%; dyspnea: 21.1%; 95% CI, 13.2% to 30.3%). The chest CT findings exhibited no significant differences between the groups.Conclusion. Fever was found to be the most common symptom in COVID-19, and respiratory infection signs were also commonly present. Fever and dyspnea were less frequently observed in the patients diagnosed outside of Wuhan, which should be considered in COVID-19 screening programs. These results may be attributable to the earlier diagnosis of the disease and the younger age of patients outside of Wuhan although further analysis is needed. The role of chest CT in COVID-19 diagnosis is inconclusive based on this study.

Objectives The objective of this study was to evaluate the effects of allergic rhinitis (AR) on the development, progression, and recovery of acute otitis media (OM) in an animal model and investigate the secondary effects of bacterial infection. Methods BALB/c mice were divided into four groups: AR + OM, AR, OM, and control groups. AR + OM and AR groups were sensitized with ovalbumin (OVA) and alum and then challenged intranasally with OVA. Phosphate-buffered saline (PBS) was administered to the OM and control groups the same number of times. After AR induction, OM was induced by surgical inoculation of non-typeable Haemophilus influenza (NTHi) into the middle ear (ME) cavity of the mice in the AR + OM and OM groups. PBS was injected into the bulla in the AR and control groups. Each group was subdivided into sets of six mice, one for each of the four time points (0, 2, 7, and 10 days post-bacterial inoculation), at which point the mice were euthanized and ME and nasal cavity mucosa were obtained and evaluated. The occurrence of OM and the ME mucosa thickness were evaluated and compared among the four groups. Tissue expression of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) in infected ME mucosa was assessed by immunohistochemical staining. We also investigated IgE, IL-4, and IL-5 in the nasal mucosa. Results Most of the ears showed OM on post-inoculation day 2 in both AR + OM and OM groups. In the AR + OM group, 58.3% of ears still had OM on post-inoculation day 10, while only 16.7% of the OM group had OM. The ME mucosa of all groups increased, and the AR + OM group exhibited the thickest mucosa. The OM group showed peak thickness on post-inoculation day 2 and then decreased, whereas the ME mucosa thickness of the AR + OM group continued to increase to day 7. In the OM group, the expression of IL-1β, IL-6, and TNF-α in the ME also increased significantly, peaking on post-inoculation day 2, and then gradually decreased. In the AR + OM group, the expression of these proteins increased until day 7 and then decreased. The IgE and Th2 response (IL-4 and IL-5) cytokines were expressed at higher levels in the AR + OM and AR groups than in the OM and control groups. Conclusion The inflammatory reaction to NTHi was more intense and lasted longer in the allergic group, which indicates that AR affects the progression and subsequent recovery of acute bacterial OM.

Background/Aim: This study aimed to investigate changes in the tracheal mucosa after thyroidectomy, that can be a cause of post-thyroidectomy discomfort. Materials and Methods: Forty rats were divided into normal controls and 3 surgical groups: (i) thyroid isthmectomy with cauterization, (ii) isthmectomy by a cold instrument without hemostasis, and (iii) sham (exposure of the trachea and thyroid gland without thyroidectomy by dissection through pretracheal fascia). Animals were euthanized at 1 and 4 weeks. Mucosal edema and glandular hyperplasia were measured. Mucin production and basal cell activities were evaluated by mucin 5AC (MUC5AC) and keratin 5 (KRT5) using immunofluorescence staining. Results: Larger mucosal areas were observed in all surgical groups at 1 and 4 weeks. More submucosal glandular hyperplasia was noted in the group with isthmectomy without hemostasis. MUC5AC and KRT5 expressions were significantly higher in the surgical groups. Conclusion: The tracheal mucosa may change after surgery, which could explain postoperative discomfort after thyroidectomy.

The objective of this study was to investigate the expression and the role of surfactant protein A (SP-A) in the middle ear (ME) mucosa in response to bacterial infection in a rat model. Otitis media (OM) was induced by surgical inoculation of non-typeable Haemophilus influenza (NTHi) into the ME cavity of Sprague-Dawley rats. The rats were divided into an NTHi-induced OM group and a phosphate-buffered saline-injected control group. The NTHi-induced OM and control groups were subdivided into sets of 6 rats, one for each of the 6 time points (0, 1, 2, 4, 7, and 14 days post-inoculation), at which point the rats were euthanized after inoculation. The concentrations of SP-A in the ME effusion were determined by an enzyme-linked immunosorbent assay (ELISA). Tissue expression of SP-A, interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in infected ME mucosa was assessed by immunohistochemical staining. For mRNA expression quantification, RNA was extracted from the ME mucosa and SP-A expression was monitored and compared between the control and OM groups using quantitative polymerase chain reaction (PCR). Expression of IL-1β, IL-6, and TNF-α in the ME mucosa was also evaluated. SP-A expression was evaluated in the effusion of pediatric OM patients (70 ears) who received ventilation-tube insertion by ELISA. SP-A was detected in normal rat ME mucosa before bacterial inoculation. SP-A expression was up-regulated in the NTHi-induced OM group (p = 0.046). Immunohistochemical staining revealed increased SP-A expression on post-inoculation day 1, 2, and 4 in the OM group. Expression of proinflammatory cytokines (IL-1β, IL-6, and TNF-α) in the ME also increased significantly on post-inoculation day 1, 2, and 4 in the OM group. It correlated with changes in SP-A expression. Expression of SP-A was also identified in the ME effusion of humans. SP-A exists in the ME of the rat and was up-regulated in the ME of NTHi-induced OM. Expression of IL-1β, IL-6, and TNF-α was increased in the ME of the bacteria-induced OM in the rat model. The results suggest that SP-A may play a significant role in the early phase of OM induction and subsequent recovery from it.

Objective: To investigate whether otoacoustic emissions (OAEs) are impaired in patients with myasthenia gravis (MG) and whether such dysfunction is associated with serological and electrophysiological features of MG.Methods: We tested 15 patients with MG (30 ears) and 10 healthy age- and sex-matched subjects (20 ears) for transiently evoked OAE (TEOAE) and distortion product OAE (DPOAE).Results: Compared with controls, MG patients revealed a significant reduction in the amplitude of TEOAEs (p < 0.05) and DPOAEs at higher frequencies between 2,026 and 4,053 Hz (p < 0.05). In the subgroup analysis, TEOAE and DPOAE amplitudes were significantly lower in the acetylcholine receptor (AChR) antibody-positive group (p < 0.05) as well as in the repetitive nerve stimulation (RNS)-positive (p < 0.05) group. In particular, the OAE alteration significantly correlated with anti-AChR antibody titers. No significant difference of the OAEs was found between thymomatous and non-thymomatous MG or between purely ocular and generalized MG.Conclusions: Our study confirms that OAEs reveal subclinical dysfunction of the cholinergic neurotransmission of cochlear outer hair cells and correlate well with electrophysiological and serological characteristics of MG patients. Our findings imply that the measurement of OAEs might increase the diagnostic accuracy and help to monitor the severity of MG.

The objective of this study was to evaluate the role of group 3 innate lymphoid cells (ILC3) in the middle ear (ME) mucosal response to bacterial infection in a rat model. To confirm the role of ILC3 in bacterially induced otitis media (OM), the serum concentrations of IL-17 and IL-22 were determined by ELISA, and the tissue expression of IL-17 and IL-22 in infected ME mucosa was assessed by immunohistochemical staining. Immunohistochemical staining of specific cell surface markers was also assessed to confirm the origin of the cells expressing IL-17 and IL-22. Twenty Sprague-Dawley rats were used in the surgically-induced animal model of OM. OM was induced by inoculation of non-typeable Haemophilus influenzae into the ME cavity of the rats. The rats were divided into four experimental groups: three infected groups and one control group. Infected groups were subdivided into sets of 5 rats, one for each of the three time points (1, 4 and 7 days post-inoculation). For determination of rat IL-17 and IL-22 levels in infected rats and control rats, infected or control ME mucosa sections were analyzed by immunohistochemistry with specific antibodies directed against IL-17 and IL-22. Immunohistochemical staining for CD3, RORγt, and NKp46 were also conducted on the samples to confirm the origin of cells expressing IL-17 and IL-22. IL-17 and IL-22 serum concentrations were significantly increased in the infected rats compared to control rats. Immunohistochemical staining revealed increased IL-17 and IL-22 expressions in all infected ME mucosae from the first day after inoculation. In addition, the results of tissue staining for the specific surface markers were negative for CD3 and NKp46, but were highly positive for RORγt. IL-17 and IL-22 revealed their association with the bacterially induced proliferative and hyperplastic responses of ME mucosa, which are characteristic features in pathogenesis of OM. Surface marker examination showed that the source cells for IL-17 and IL-22 seemed to be lymphoid tissue inducer (LTi) cells. The results suggest that LTi cells release IL-17 and IL-22, and play a significant role in both the early phase of OM induction and recovery from it.

Objectives/Hypothesis Oral ulcers are very common and can compromise the quality of life of patients with pain. The objective of this study was to evaluate mucosal healing with curcumin in an animal oral ulcer model. Study Design Experimental study. Methods Twenty New Zealand white rabbits were used. Round filter paper 6 mm in diameter was soaked with 15 μl 50% acetic acid and applied over the upper labial gingiva, creating a uniform circular ulcer. After creation of an oral ulcer, curcumin, the active substance in tumeric, was applied twice over the ulcer in the experimental group but not in the control group. The ulcer area was calculated by maximal (D) and minimal (d) diameter : π × D × d/4. All animals were weighed, and the area was measured on days 0, 7, and 14. On days 7 and 14, half of the animals were sacrificed and gingival specimens were acquired. Results Curcumin treatment exhibited accelerated healing such that the gross appearance of the ulcer demonstrated a recognizable difference in wound healing between the curcumin-treated and control groups with time. Weight loss was observed after the creation of oral ulcer in the control group. However, the curcumin-treated group gained weight with time, resulting in a significant weight difference. On day 14, epithelial regeneration was completed in the treated group but incomplete in the control group. Conclusion Topical application of curcumin enhanced the wound-healing process of oral ulcer in the animal model, which implicate that curcumin can be used as an effective and safe medical tool in the treatment of oral ulcer. Level of Evidence NA. Laryngoscope, 2015

Introduction: Glucocorticoids are considered the first-line therapy for sudden sensorineural hearing loss. But there is currently no consensus on administering them as a single dose versus multiple divided daily doses. Objective: We aim to evaluate the treatment outcome of sudden sensorineural hearing loss between a single-dose and multiple divided daily doses of steroid treatment. Methods: A total of 94 patients who were diagnosed and treated for sudden sensorineural hearing loss and followed up for more than three months were reviewed retrospectively. Patients were divided into single-dose and multiple divided-dose groups, based on their medication regimens. Hearing thresholds were repeatedly measured: on the initial visit and 1 week, 1 month, and 3 months after the initial treatment. Treatment outcomes were analyzed by comparing hearing recovery rates and post-treatment audiometric changes. Results: The hearing threshold was significantly reduced at three months post-treatment in both groups. The hearing recovery rate of the single-dose group was significantly higher than that of the multiple divided-dose groups. Audiometric changes showed no statistical difference either in pure tone threshold or speech discrimination. Conclusion: When oral steroids are indicated for sudden sensorineural hearing loss, both a single dose and multiple divided doses can be effective for treatment and have comparable results. However, the single-dose regimen seems to be more efficacious than the divided-dose regimen. Resumo: Introdução: Os glicocorticoides são considerados terapia de primeira linha para perda auditiva neurossensorial súbita. Contudo, atualmente não há consenso em como para administrá-los, se em dose única ou múltiplas doses diárias. Objetivo: Nosso objetivo é avaliar o resultado do tratamento da perda auditiva neurossensorial súbita com uma dose única ou várias doses diárias de tratamento com esteróides. Método: Um total de 94 pacientes que foram diagnosticados e tratados para perda auditiva neurossensorial súbita e acompanhados por mais de três meses pós-tratamento foram avaliados retrospectivamente. Os pacientes foram divididos em grupos de dose única diária e dose diária dividida em múltiplas tomadas, baseado em seu regime medicamentoso. Os limiares auditivos foram medidos repetidamente: na visita inicial e em 1 semana, 1 mês e 3 meses após o tratamento inicial. Os resultados do tratamento foram analisados comparando-se as taxas de recuperação da audição e as alterações audiométricas pós-tratamento. Resultados: O limiar auditivo foi significativamente reduzido aos três meses pós-tratamento em ambos os grupos. A taxa de recuperação auditiva no grupo de dose única foi significativamente maior do que no grupo de dose diária dividida em múltiplas tomadas. As alterações audiométricas não mostraram diferença estatística, tanto no limiar de tom puro quanto na discriminação da fala. Conclusão: Quando esteroides orais são indicados para perda auditiva neurossensorial súbita, tanto uma dose única quanto múltiplas doses podem ser eficazes para o tratamento e têm resultados comparáveis. No entanto, o regime de dose única diária parece ser mais eficaz do que o regime de dose diária dividida em múltiplas tomadas. Keywords: Sudden sensorineural hearing loss, Steroid, Dose, Regimen, Palavras-chave: Perda auditiva neurossensorial súbita, Esteroide, Dose, Regime

BACKGROUND We hypothesize that excessive fibrin formation and inflammation induced by antiadhesive material, SurgiWrap (SW), would have an adverse effect on wound healing. It was evaluated by a thyroidectomy murine wound model. METHODS Excessive fibrin formation was induced by isthmectomy without hemostasis. Rats were allocated into isthmectomy with SurgiWrap (I+SW+), I+SW-, I-SW+, I-SW-, and isthmectomy after electrocautery for hemostasis (I+C+SW-). The SWs were placed on the superficial and visceral layers for gross and microscopic evaluation. RESULTS Microscopic examination showed collagen deposition occurred in the I-SW- sham group and at a higher level in I+C+SW-. The collagen deposition decreased in groups without SW with time but increased in groups with SW. Use of SW produced more inflammation and more collagen deposition. The I+SW + group developed the largest area of collagen deposition at 4 weeks and more collagen deposition than the I-SW + group. CONCLUSION The SW induced more collagen deposition increasing with time. The collagen deposition produced by SW was worsened by excessive fibrin formation and inflammation.

Injection laryngoplasty is widely used for treatment of vocal fold palsy. To test the efficacy and safety of newly developed injection materials for vocal fold augmentation, we need reliable animal model for objective evaluation of glottal insufficiency. In this study, we aimed to develop an animal model to quantitatively evaluate the histological and functional changes of the paralyzed vocal fold. Left side recurrent laryngeal nerves were identified at tracheoesophageal groove of the New Zealand white rabbits and they were resected. Endoscopic examination was performed immediately after operation and 1, 2, 4, 8, 12 week after the operation to identify left vocal fold immobility. Total laryngectomy was performed 1, 2, 4, 8, 12 weeks after the operation. We have developed the method to quantify the changes of the intralaryngeal muscles. Histologic exam revealed significant decrease in thyroarytenoid muscle volume in the paralyzed side 12 weeks after the operation. We have also developed the method to quantify the laryngeal functions by analyzing vocal fold vibration. High speed recording of induced phonation showed irregular and asymmetric movement of vocal fold in the glottal insufficiency model. Videokymographic analysis showed increased open quotient and asymmetric index compared with the normal vocal fold. This model could be used to provide fundamental changes related with vocal fold paralysis. Even more, this animal model could be utilized to test efficacy and safety of various injection materials to augment the vocal fold.

Background Congenital and acquired tracheal stenosis continues to be challenging problems. The purpose of this study was to evaluate the efficacy of an asymmetrically porous membrane (APM) to induce tracheal reconstruction by inhibition of granulation tissue growth into the tracheal lumen whereas minimizing graft failure. Methods The APM was fabricated with polycaprolactone (PCL) and pluronic F127 to have nano-size pores at top side, whereas the bottom side had micro-size pores. Fifteen rabbits underwent tracheal defect, which was then reconstructed with the APM. Rabbits were euthanized 1, 4, and 12 weeks postoperatively, and endoscopic, histologic, and radiologic evaluations were conducted. Results Endoscopy did not reveal granulation ingrowth into tracheal lumen. APM was well incorporated into the surrounding tissue on histologic evaluation. CT scans showed well maintained airways. Conclusion Off-the-shelf use of APM for tracheal reconstruction seems to be a promising strategy in the treatment of tracheal defects. © 2013 Wiley Periodicals, Inc. Head Neck 36: 643–651, 2014

A major aspect of pathology in otitis media (OM), the most common childhood bacterial disease, is hyperplasia of the middle ear mucosa. Activation of innate immune receptors during OM leads to the activation of NF-κB, a pleiotropic transcription factor involved both in inflammation and tissue growth. To explore the role of NF-κB in mucosal hyperplasia during OM, we evaluated the expression of genes involved in two modes of NF-κB activation during a complete episode of acute, bacterial OM in mice. We also determined the effects of inhibitors of each pathway on infection-stimulated mucosal growth in vitro. A majority of the genes that mediate both the canonical and the non-canonical pathways of NF-κB activation were regulated during OM, many with kinetics related to the time course of mucosal hyperplasia. Inhibition of either pathway reduced the growth of cultured mucosal explants in a dose-dependent manner. However, inhibition of the canonical pathway produced a greater effect, suggesting that this mode of NF-κB activation dominates mucosal hyperplasia during OM.

In this study, the gene expression profile of early in vitro Streptococcus pneumoniae biofilm with respect to planktonic cells in cDNA microarray analysis is reported. Microarray analysis with respect to planktonic cells was performed on total RNA extracted from biofilms grown in 24-well microtiter plates. To validate the microarray results, real-time RT-PCR was performed on 13 differentially expressed genes and one constitutively expressed gene. The cDNA-microarray analyses identified 89 genes that were significantly differentially expressed in biofilm and planktonic cells. Genes involved in isoprenoid biosynthesis, cell wall biosynthesis, translation and purine and pyrimidine nucleotide metabolic pathways were exclusively expressed in the biofilms, whereas transcription regulator genes were exclusively expressed in planktonic cells. The real-time RT-PCR results of 13 differentially regulated genes were completely in agreement with the microarray data. The exclusive up regulation in biofilms of genes involved in the mevalonate pathway, cell wall biosynthesis, translation and purine and pyrimidine nucleotide metabolic pathways suggests that expression of these genes may be required for initial biofilm formation, and growth and survival of bacteria in biofilms. The up regulation of related genes suggests that cells in biofilms may be under stress conditions and possibly actively involved in the protein synthesis required to adapt to a new environment.

The expression of all three subunits of the epithelial sodium channel (ENaC) decreased after the lipopolysaccharide (LPS) injection and normalized as the fluid collection resolved. This implies that fluid collection in acute otitis media may be caused by the inhibition of ENaC function.We investigated the expression levels of subunits of ENaC after an injection of LPS into the middle ear cavity of rats.Seventy-two Sprague-Dawley rats were assigned randomly into the five groups that received an LPS injection and the control group. A transtympanic injection of LPS (1 mg/ml) was done and rats were sacrificed 6, 12, 24, 72, and 120 h after the procedure. Real-time RT-PCR was carried out for ENaC-α, -β, -γ, and immunohistochemistry was performed for ENaC-α and -β.The level of ENaC-α expression decreased 0.50-fold and 0.55-fold at 6 and 12 h, respectively (p0.05), but it normalized at 24 h. It increased 3.64-fold at 72 h and 3.24-fold at 120 h (p0.05). At 6 and 12 h after the LPS injection into the middle ear cavity, inflammation was induced and ENaC-α immunoreactivity decreased. At 24 h, ENaC-α immunoreactivity was normalized, then at 72 and 120 h after the injection it was increased.

Aim The increasing number of newborns requiring intubation and artificial ventilation in the sophisticated premature and intensive care units of recent years has been followed by a concomitant increase in the number of children who develop tracheal stenosis as a sequela of prolonged intubation, with a consequent increasing need for tracheal surgical repair. The aim of this study was to evaluate tracheal reconstruction by monolayered autologous mesenchymal stem cells (MSCs) with small intestine submucosa (SIS) in a rabbit model. Methods Twelve male rabbits were randomly divided into three groups: rabbits with tracheal defects without reconstruction (untreated group, n = 4), rabbits with tracheal defects given porcine small intestine submucosa graft (SIS group, n = 4), and rabbits with tracheal defects that underwent transplantation of monolayered mesenchymal stem cells on SIS (SIS+MSC group, n = 4). Histological and endoscopic analyses were performed by hematoxylin–eosin staining (H&E), Prussian blue staining and endoscopy. Results Tracheal stenosis in the SIS+MSC group was minimal, compared to the untreated group and SIS group. Specimens obtained from the untreated and SIS groups showed severe infiltration of inflammatory cells and granulation tissue formation into the trachea. In the SIS+MSC group, however, minimal infiltration of the inflammatory cells and granulation tissue formation were observed. Twelve weeks following the operation, regeneration of pseudostratified columnar epithelium was confirmed by H&E staining with minimal inflammatory cell infiltration in the SIS+MSC group. Moreover, Prussian blue staining clearly demonstrated the presence of labeled MSCs in the regenerated tissue of SIS+MSC group. Conclusions These results demonstrate that tracheal reconstruction by MSCs with SIS is effective in rabbits with tracheal defects with minimal mortality and morbidity, which appears to be a promising strategy in the treatment of tracheal defects.

Background Vitamin D plays an important role in the immune response against infection. The purpose of the present study was to investigate the influence of vitamin D deficiency on the progression of otitis media (OM) using an experimental rat model. Methods Four-week-old male Sprague-Dawley rats (n=72) were divided into two groups based on their diet: a control diet group (n=36) and a vitamin D-deficient diet group (n=36). After 8 weeks of diet, experimental OM was induced by inoculation of non-typeable Haemophilus influenzae in the middle ear cavity. The rats were evaluated with otomicroscopy to determine the inflammation in the middle ear mucosa on days 1, 2, 4, 7, and 14 post-inoculation. Bullae from sacrificed rats were collected and analyzed histologically. Results The middle ear mucosa from rats with vitamin D deficiency showed a significantly higher thickness than that of controls during the course of OM. The maximum mucosal thickness was 56.0±9.1 μm in the vitamin D deficiency group, and 43.9±9.8 μm in the control group, although there was no significant difference in the tympanic membrane score between the two groups evaluated with otomicroscopy. An immunohistochemical study showed increased expression of interleukin 6 (IL-6) and tumor necrosis factor α in rats manifesting vitamin D deficiency and decreased expression of IL-10 compared with controls. Conclusion Our results showed that vitamin D deficiency may exacerbate the pathophysiological changes of OM via altered cytokine production. Therefore, maintaining vitamin D status in the optimal range may be beneficial for proper management of OM.

CHARGE syndrome was first described by Pagon, and was named for its six major clinical features, which are; coloboma of the eye, heart defects, atresia of the choanae, retarded growth and developmental anomalies, which include CNS anomalies, genital hypoplasia and/or urinary tract anomalies, and ear anomalies and/or hearing loss. The authors experienced a case of CHARGE syndrome that displayed bilateral jugular foramen atresia and a collateral emissary vein. In addition, the authors reviewed the literatures pertaining to CHARGE syndrome.

Summary Objectives Myringosclerosis is a common sequela of ventilation tube insertion for the treatment of the otitis media with effusion. Several antioxidants have been identified to prevent myringosclerosis. The objective of this study was to investigate the effect of caffeic acid phenethyl ester (CAPE) on the prevention of experimentally induced myringosclerosis. Methods Thirty-five Sprague–Dawley rats were unilaterally myringotomized. The rats were divided into four groups randomly: group 1 received no treatment, group 2 received intraperitoneally administered saline and group 3 received intraperitoneally administered CAPE. The tympanic membranes were examined by otomicroscopy on the 15th day after treatment. The membranes were then harvested and evaluated histologically by light microscopy. Results The tympanic membranes from group 1 showed extensive myringosclerosis; those from group 2 showed a similar occurrence of myringosclerosis. However, group 3 had a reduced occurrence of myringosclerosis by otomicroscopic evaluation. Under light microscopic examination, the lamina propria of the pars tensa was found to be thicker and more sclerotic in groups 1 and 2 when compared with group 3. Conclusions Systemic treatment with CAPE was found to be effective in the prevention of sclerotic lesions in myringotomized rat tympanic membranes.

Oral ulcers are very common and can compromise the quality of life of patients with pain. The objective of this study was to evaluate mucosal healing with curcumin in an animal oral ulcer model.Experimental study.Twenty New Zealand white rabbits were used. Round filter paper 6 mm in diameter was soaked with 15 μl 50% acetic acid and applied over the upper labial gingiva, creating a uniform circular ulcer. After creation of an oral ulcer, curcumin, the active substance in tumeric, was applied twice over the ulcer in the experimental group but not in the control group. The ulcer area was calculated by maximal (D) and minimal (d) diameter : π × D × d/4. All animals were weighed, and the area was measured on days 0, 7, and 14. On days 7 and 14, half of the animals were sacrificed and gingival specimens were acquired.Curcumin treatment exhibited accelerated healing such that the gross appearance of the ulcer demonstrated a recognizable difference in wound healing between the curcumin-treated and control groups with time. Weight loss was observed after the creation of oral ulcer in the control group. However, the curcumin-treated group gained weight with time, resulting in a significant weight difference. On day 14, epithelial regeneration was completed in the treated group but incomplete in the control group.Topical application of curcumin enhanced the wound-healing process of oral ulcer in the animal model, which implicate that curcumin can be used as an effective and safe medical tool in the treatment of oral ulcer.NA.

The GSTP1 and NQO1 have been reported to be associated with an increased risk for smoking related head and neck squamous cell carcinoma (HNSCC). The purpose of this study was to determine the effect of these metabolic gene polymorphisms on the risk of HNSCC. The study population included 294 histologically confirmed HNSCC cases and 333 controls without cancer. Genotyping analysis of the GSTP1 Ile105Val and NQO1 Trp139Arg genes was performed by polymerase chain reaction-based techniques on DNA prepared from peripheral blood. The Mantel-Haenszel chi2 test was used for statistical analysis. The allele frequencies of the GSTP1 and NQO1 polymorphisms were not statistically significant between cases and controls. In analyzing the association between smoking amounts and genetic polymorphisms, GSTP1 and NQO1 polymorphisms were associated with cigarette smoking amounts in cases. G allele containing genotypes in GSTP1 and T allele containing genotypes in NQO1 were associated with a tobacco dose-dependent increase in risk of HNSCC and these genotype distributions were statistically significant (p0.05). We found that the GSTP1 105Val allele and NQO1 139Arg allele were associated with tobacco dose-dependent increase in risk of HNSCC. GSTP1 and NQO1 genotype polymorphisms may play an important role in the development of smoking related HNSCC.

There is increasing demand for reconstruction of glottal insufficiency. Several injection materials have been examined for this purpose, but all had limitations, such as poor long-term durability, migration from the injection site, inflammation, granuloma formation, and interference with vocal fold vibration due to viscoelastic mismatch. Here, we developed a novel injection material, consisting of polycaprolactone (PCL) microspheres, which exhibits better viscoelasticity than conventional materials, and Pluronic F127 carrier, which decreases the migration of the injection materials. The material was injected into rabbits with glottal insufficiency and compared with the FDA-approved injection material, calcium hydroxylapatite (CaHA). Endoscopic and histological examinations indicated that PCL/Pluronic F127 remained at the injection site with no inflammatory response or granuloma formation, whereas CaHA leaked out and migrated from the injection site. Therefore, vocal fold augmentation was almost completely retained during the 12-month follow-up period in this study. Moreover, induced phonation and high-speed recording of vocal fold vibration showed decreased vocal fold gap area in the PCL/Pluronic F127 group. Our newly developed injection material, PCL/Pluronic F127, permits efficient augmentation of paralyzed vocal fold without complications, a concept that can be applied clinically, as demonstrated by the successful long-term follow-up.

Objectives. Based on studies of the extensive tropism of neural stem cells (NSCs) toward malignant brain tumor, we hypothesized that NSCs could also target head and neck squamous cell carcinoma (HNSCC) and could be used as a cellular therapeutic delivery system. Methods. To apply this strategy to the treatment of HNSCC, we used a human NSC line expressing cytosine deaminase (HB1.F3-CD), an enzyme that converts 5-fluorocytosine (5-FC) into 5-fluorouracil (5-FU), an anticancer agent. HB1. F3-CD in combination with 5-FC were cocultured with the HNSCC (SNU-1041) to examine the cytotoxicity on target tumor cells in vitro. For in vivo studies, an HNSCC mouse model was created by subcutaneous implantation of human HNSCC cells into athymic nude mice. HB1.F3-CD cells were injected into mice using tumoral, peritumoral, or intravenous injections, followed by systemic 5-FC administration. Results. In vitro, the HB1.F3-CD cells significantly inhibited the growth of an HNSCC cell line in the presence of the 5-FC. Independent of the method of injection, the HB1.F3-CD cells migrated to the HNSCC tumor, causing a significant reduction in tumor volume. In comparison to 5-FU administration, HB1.F3-CD cell injection followed by 5-FC administration reduced systemic toxicity, but achieved the same level of therapeutic efficacy. Conclusion. Transplantation of human NSCs that express the suicide enzyme cytosine deaminase combined with systemic administration of the prodrug 5-FC may be an effective regimen for the treatment of HNSCC.

Congenital and acquired tracheal stenosis continues to be challenging problems. The purpose of this study was to evaluate the efficacy of an asymmetrically porous membrane (APM) to induce tracheal reconstruction by inhibition of granulation tissue growth into the tracheal lumen whereas minimizing graft failure.The APM was fabricated with polycaprolactone (PCL) and pluronic F127 to have nano-size pores at top side, whereas the bottom side had micro-size pores. Fifteen rabbits underwent tracheal defect, which was then reconstructed with the APM. Rabbits were euthanized 1, 4, and 12 weeks postoperatively, and endoscopic, histologic, and radiologic evaluations were conducted.Endoscopy did not reveal granulation ingrowth into tracheal lumen. APM was well incorporated into the surrounding tissue on histologic evaluation. CT scans showed well maintained airways.Off-the-shelf use of APM for tracheal reconstruction seems to be a promising strategy in the treatment of tracheal defects.

Background and ObjectivesZZSeveral prognostic factors are known to be related to the recovery of sudden sensorineural hearing loss (SSNHL). Recent studies have suggested that cardiovascular risk factors (CVRFs) are associated with the occurrence of SSNHL. However, the value of CVRFs as a predictor of recovery in patients with SSNHL has been rarely evaluated. We aim to evaluate the prognostic value of CVRFs in relation to hearing recovery of SSNHL. Subjects and MethodZZA total of 278 patients who were diagnosed and treated for SSNHL and who underwent blood sampling and follow-ups for more than 3 months were reviewed retrospectively. We reviewed CVRFs such as age, body mass index, blood pressure, cholesterol, smoking history, the presence of diabetes mellitus and other related underlying diseases. Patients were divided into three groups (low, medium, and high CVRF groups) according to the CVRF grades. Hearing thresholds were repeatedly measured on the initial visit, 1 week, 1 month and 3 months after treatment. Treatment outcome was analyzed by comparing hearing recovery rate and post-treatment audiometric changes among the three CVRF groups. ResultsZZSeventy (25.2%), 129 (46.4%) and 79 (28.4%) patients were included into the low, medium and high CVRF groups, respectively. The hearing threshold was significantly reduced at 3 months after treatment in all three groups (p＜0.001). The hearing recovery rate of the low CVRF group was significantly higher than that of the medium and high CVRF group (p=0.011). On the last visit, the high CVRF group significantly showed more poor hearing im provement than the low CVRF group did (p=0.045). ConclusionZZOur findings suggest that the presence of CVRFs may be a poor prognostic sign for hearing recovery in patients with SSNHL.

Objectives/Hypothesis The purpose of this study was to explore a novel strategy to restore vocal gap by using polycaprolactone (PCL) spheres with thermosensitive Pluronic F127 in a paralyzed rabbit vocal fold. Study Design In vivo study using a rabbit model. Methods The PCL spheres were fabricated by an isolated particle-melting method. The PCL spheres/Pluronic F127 gel mixture was prepared by a simple mixture of PCL and Pluronic F127 solution. We used 33 New Zealand white rabbits, which were divided into normal (n = 3), vocal fold palsy (VFP, n = 12), PCL/Pluronic F127 gel mixture (PCL, n = 12), and Radiesse (n = 6) groups. After unilateral recurrent laryngeal nerve section, PCL or Radiesse were injected into paralyzed vocal folds. Laryngoscopic exams were performed 1, 2, 4, and 12 weeks after implantation; then larynx specimens were sampled. High-speed camera recording of vocal fold vibration and evaluation by videokymography were performed. Open quotient and asymmetric index were calculated. We evaluated the volume of the implants over time and investigated histologic changes. Results Endoscopic analysis showed that PCL/Pluronic F127 gel mixture maintained its volume without migration or inflammatory response. Vocal fold gap decreased and asymmetric vocal fold movement was improved compared with the VFP group. Histologically, connective tissue growth was observed between the spheres. The remaining volume of injected material was greater than the Radiesse group, without statistical significance. Conclusions Locally injected PCL/Pluronic F127 can enhance glottal contact, suggesting it as a potential new therapeutic approach that may lead to better treatment of vocal fold palsy. Level of Evidence N/A. Laryngoscope, 2013

In this study, the gene expression profile of early in vitro Streptococcus pneumoniae biofilm with respect to planktonic cells in cDNA microarray analysis is reported. Microarray analysis with respect to planktonic cells was performed on total RNA extracted from biofilms grown in 24-well microtiter plates. To validate the microarray results, real-time RT-PCR was performed on 13 differentially expressed genes and one constitutively expressed gene. The cDNA-microarray analyses identified 89 genes that were significantly differentially expressed in biofilm and planktonic cells. Genes involved in isoprenoid biosynthesis, cell wall biosynthesis, translation and purine and pyrimidine nucleotide metabolic pathways were exclusively expressed in the biofilms, whereas transcription regulator genes were exclusively expressed in planktonic cells. The real-time RT-PCR results of 13 differentially regulated genes were completely in agreement with the microarray data. The exclusive up regulation in biofilms of genes involved in the mevalonate pathway, cell wall biosynthesis, translation and purine and pyrimidine nucleotide metabolic pathways suggests that expression of these genes may be required for initial biofilm formation, and growth and survival of bacteria in biofilms. The up regulation of related genes suggests that cells in biofilms may be under stress conditions and possibly actively involved in the protein synthesis required to adapt to a new environment.

Objective: 1) Know the factors that can affect the amount of blood loss or the change of the hemoglobin or hematocrit level after adenotonsillectomy in children. 2) Find any quantitative correlations between factors and bleeding parameters.Method: From 172 child patients receiving adenotonsillectomy, CBC was measured before and after surgery, and then hemoglobin and hematocrit loss percent was calculated respectively. We selected some factors that can affect operative bleeding parameters. Data were analyzed to find any correlation between the factors and bleeding parameters.Results: Data were statistically analyzed with two-tailed Spearman’s rho correlation test and multiple linear regression. Patient body weight factor correlated significantly with hemoglobin (P = .018) or hematocrit loss percent (P = .036), but not with estimated bleeding amount. Regression equation was [Hemoglobin loss percent = 7.172 - 0.096x (body weight)(P = .015)] and [hematocrit loss percent = 6.267 - 0.086x (body weight) (P = .02...

Objectives The primary aim of this study was to reveal the relationship between inflammatory response of human middle ear epithelial cell (HMEEC) and microRNA (miRNA). Methods In experimental group, cells were treated with lipopolysaccharide (LPS) for 2 h. No LPS was treated in the control group. Total RNA was extractedand used for miRNA microarray analysis. The predicted targets of miRNA with significant change were obtained using miRBase. To assess the function of predicted target gene lists, we evaluated the frequency of specific gene ontology (GO) terms among the predicted target genes of the miRNA with significant change using DAVID (Database for Annotation, Visualization and Integrated Discovery). Results After normalization, the number of the differentially expressed genes was 15. Among them, 5 miRNAs were up-regulated and 10 miRNAs were down-regulated in LPS group compared with control group. The most enriched GO terms in the predicted target genes of miRNA with increased expression were developmental process, response to biotic stimulus, acute inflammatory response, and regulation of cell growth. The most enriched GO terms in the predicted target genes of miRNA with decreased expression were developmental process, cell differentiation, endocytosis, cell communication, IκB kinase/NFκB cascade, complement activation, innate immune response and cell adhesion. Conclusions In conclusion, we identified the differentially expressed miRNA in LPS induced acute inflammation of HMEECs whose expression profile may provide a useful clue for the understanding of pathophysiology of otitis media. Our work indicates that miRNA play important role in the pathogenesis of otitis media.

Objective Guggulsterone is a bioactive constituent of resinous sap originating from the guggul tree, Commiphora mukul , which has been used over several thousands of years to treat various diseases, including atherosclerosis, rheumatism, and obesity. However, the effect of guggulsterone inflammatory reactions induced by lipopolysaccharide (LSP) is not known. The aim of this study was to evaluate the anti-inflammatory effect of guggulsterone on cultured human middle ear epithelial cells (HMEEC). Methods The effect of guggulsterone on LPS-induced tumor necrosis factor-alpha (TNF-α) and cyclooxygenase-2 (COX-2) expression was evaluated in HMEEC by real-time reverse transcription polymerase chain reaction (RT-PCR). LPS-induced COX-2 production and degradation of the inhibitor kB-alpha (IkB-α) were determined by Western blot analysis. Results Guggulsterone significantly inhibited LPS-induced upregulation of TNF-α and COX-2 in a dose-dependent manner. COX-2 protein production by LPS was significantly suppressed by the guggulsterone pretreatment. Furthermore, LPS-induced IkB-α degradation was suppressed by the guggulsterone pretreatment. Conclusions These results show that the guggulsterone has inhibitory effect on TNF-α expression and COX-2 production and it may be mediated through its inhibition of nuclear factor-kB activation. Our findings provide an insight into the molecular mechanisms underlying the anti-inflammatory activities of guggulsterone in relationship to otitis media.

The results suggest that the anti-inflammatory effect of caffeic acid phenethyl ester (CAPE) is due to its inhibition of tumor necrosis factor (TNF)-alpha expression and interleukin (IL)-8 production. The anti-inflammatory effect of CAPE is possibly through the inhibition of nuclear factor (NF)-kappaB via the suppression of inhibitor-kappaB-alpha (IkappaB-alpha) degradation.CAPE is a biologically active component of propolis, a resinous material obtained from bee hives, which originates from conifer bark. The effect of CAPE on lipopolysaccharide (LPS)-induced inflammatory reactions is not known. The aim of this study was to evaluate the anti-inflammatory effect of CAPE on cultured human middle ear epithelial cells (HMEECs).The effect of CAPE on LPS-induced TNF-alpha expression was evaluated in HMEECs by real-time reverse transcription polymerase chain reaction (RT-PCR). LPS-induced IL-8 production was determined by enzyme-linked immunosorbent assay (ELISA), and LPS-induced IkappaB-alpha degradation was followed by Western blot analysis.CAPE significantly inhibited LPS-induced up-regulation of TNF-alpha in a dose-dependent manner. IL-8 production by LPS was significantly suppressed by the CAPE pretreatment. Furthermore, LPS-induced IkappaB-alpha degradation was suppressed by the CAPE pretreatment.

중이염은 소아기에 가장 흔히 발생하는 질환 중의 하나이며, 3세 이하의 연령에서 3명 중 2명의 비율로 1회 이상 앓게 되고, 이 가운데 20% 이상에서 반복성 혹은 만성 삼출성 중이염으 로 진행한다고 알려져 있다. 반복성 혹은 만성 삼출성 중이 염은 소아기에 오래 지속되는 전음성 난청을 초래하여 언어, 학습 능력의 장애를 초래할 수 있으며, 또한 내이 기능에 장애 를 야기하여 감각신경성 난청을 유발시킬 수 있다. 국내 보고 에 의하면 15세 미만의 대상군에서 급성 중이염은 0.08%, 삼 출성 중이염은 1.22%의 유병률이 보고된 바 있다. 중이염은 다양한 원인이 복합적으로 작용하여 발생한다. 이관 기능의 장애, 면역기능의 성숙도, 세균 감염 및 유전적 요 인 등이 중이염의 발생과 치유 과정에 연관되어 있다. 또한, 흡 연에의 노출, 모유 수유, 집단 보육시설에 다니는지의 여부와 같은 환경적인 요인도 중이염의 발생에 영향을 줄 수 있는 중 요한 요인들로 알려져 있다. 중이염의 병인은 매우 다양하며 아직 완전히 규명되지 않았 지만 가장 큰 병리학적 특징은 중이 점막의 변형(transformation)과 과형성(hyperplasia)이다. 15~20 μm 두께의 단순 상 피로 이루어진 정상적인 상태에서의 중이 점막은 다양한 자 극에 의하여 중이염에 이환되면 점막의 두께가 1000 μm 이상 까지 증가되며, 섬모와 분비기능을 가지는 위 중층 원주상피 (pseudostratified columnar epithelium)로 변환된다. 중이 점막의 과형성과 다양한 염증세포의 점막 내 유입은 가역적 인 특징을 보여 중이염과 연관된 자극이 소실된 후 중이 점막 은 탈분화 과정(de-differentiation)을 거쳐 정상적인 모습으로 회복된다. 하지만 중이 점막의 과형성, 과증식 반응에 의한 Animal Models of Otitis Media

Background and Objectives: The aims of this study were to evaluate the relationship be- tween tinnitus and the level of anxiety and depression experienced by subjective tinnitus pa- tients, and to determine the effect of the level of anxiety and depression to the results of tinnitus treatment. Subjects and Methods: A total of 104 patients were included in this study. All the patients conducted Tinnitus Handicap Inventory (THI), Beck Depression Inventory (BDI), State Trait Anxiety Inventory 1, 2 (STAI 1, 2) to evaluate their psychometric properties. The subjective patterns of tinnitus before and after treatment were assessed through questionnaires. Re- sults: Significant correlation between THI scores and BDI, STAI 1, 2 scores were observed in the moderate and severe tinnitus group. The patients were classified into two groups depend - ing on their THI scores, and also classified into two groups according to BDI, STAI 1, 2 results. Analysis of differences after treatment indicated significantly improved VAS scores after treat - ment in all groups. Conclusions: The subjective level of tinnitus is significantly related with de - pression and anxiety symptoms when inconvenience caused by tinnitus was moderate or over. Assessments on tinnitus after treatment appeared to have improved significantly regardless of the severity of tinnitus, level of depression or anxiety disorder. Korean J Audiol 2013;17:83-89

Bilateral facial palsy is uncommon and it accounts for 0.3-2.0% of the facial palsy cases. In contrast to unilateral facial palsy, bilateral facial palsy may occur in association with a variety of neurological, infectious, neoplastic, traumatic, metabolic or degenerative disorders. Diabetes has been associated with bilateral facial palsy. Diabetes is more common among patients with bilateral facial palsy. But the correlation between diabetics and bilateral facial palsy is unclear. Herein, we report a case of a 66 year-old woman with bilateral Bell’s palsy associated with uncontrolled diabetes mellitus. � Korean J Otorhinolaryngol-Head Neck Surg 2012;55:449-52 Key WordsZZ Bilateral Bell’s palsy ㆍDiabetes mellitus.

Background and ObjectivesZZThe correlation between subjective nasal obstruction symptom and minimal cross-sectional area (MCA) of nasal cavity is uncertain. Some chemicals change subjective nasal obstruction symptoms without changing MCA. The aim of this study is to evaluate the correlation between the tactile pressure sense of nasal mucosa and the nasal obstruction symptom. Subjects and MethodZZFrom 30 healthy adult volunteers, sensitivity to pressure change (P-sensitivity) and sensitivity to MCA change (A-sensitivity) were measured for each side of the nose, respectively. P-sensitivity was obtained as the slope of the regression line which was defined as the change of visual analog scale (VAS) score of the subjective nasal pressure sense divided by the change of inflated intranasal balloon pressure. A-sensitivity was obtained as the slope of the regression line which was defined as the change of VAS score of nasal obstruc tion divided by the change of MCA measured with acoustic rhinometry in experimentally narrowed or blocked nose using pieces of sponge. ResultsZZThere was a strong correlation between P-sensitivity and A-sensitivity. In each volunteer, P-sensitivity or A-sensitivity of one side nose was well correlated with those of the opposite side, respectively. ConclusionZZBoth P-sensitivity and A-sensitivity of human nose vary from person to person, but they have a strong correlation with each other. Nasal obstruction symptom can be influ enced by change of general somatic sense of nasal mucosa. � Korean J Otorhinolaryngol-Head Neck Surg 2011;54:623-8 Key WordsZZAcoustic rhinometry ㆍNasal obstruction ㆍSensation.