IL-5 and Eotaxin Levels in Middle Ear Effusion and Blood from Asthmatics with Otitis Media with Effusion

Objective--The purpose of this study was to evaluate eosinophil infiltration as well as IL-5 and eotaxin levels in middle ear effusion (MEE) and blood from otitis media with effusion (OME) patients with asthma and to compare the findings with those from OME patients without asthma (control group). Material and methods--Levels of IL-5 and eotaxin in MEE and blood were measured by means of enzyme-linked immunosorbent assay. Results--IL-5 levels in MEE were significantly higher than those in blood in both groups of patients and in OME patients with asthma than in the control group. In addition, in OME patients with asthma, there was a significant correlation between the percentage of eosinophils and IL-5 levels in MEE. Eotaxin levels in blood were significantly higher than those in MEE in both groups of patients and in OME patients with asthma than in the control group. In addition, in OME patients with asthma, the percentage of eosinophils and eotaxin levels in blood tended to correlate, but did not reach statistical significance. Conclusion--These data suggest that, in OME patients with asthma, eosinophilia in MEE depends more on IL-5 than on eotaxin, and that eotaxin may play an important role in the mobilization of eosinophils from the bone marrow into the blood.     

Evaluation of the Interleukin-1 Receptor Antagonist and Immunoregulatory Interleukin-10 in the Middle Ear in Chronic Otitis Media With Effusion in Children With and Without Atopy

ObjectivesThe role of pro-inflammatory cytokines in the course of chronic otitis media with effusion (COME) has been documented. However, there are fewer studies on the action of anti-inflammatory cytokines in the middle ear. We sought determine whether there is an association between COME and anti-inflammatory cytokines and whether there are any differences in the cytokine profile in COME children with and without atopy.MethodsEighty-four children were divided into 3 groups: 32 nonatopic children with COME (group NA), 31 atopic children with COME (group A), and 21 children without COME and without atopy (control group C). Specimens from the middle ear were collected and evaluated by enzyme-linked immunosorbent assay for the cytokines interleukin-1 receptor antagonist (IL-1Ra) and immunoregulatory IL-10.ResultsSignificantly higher IL-10 concentrations were found in both nonatopic and atopic children with COME compared to controls. No significant differences in IL-1Ra levels were found between atopic and nonatopic children with COME and the control group.ConclusionWe found no differences in the levels of IL-1Ra in atopic and nonatopic children with COME compared to controls. However, we found elevated IL-10 levels in the middle ear effusions from children with COME, with or without atopy. These elevated immunoregulatory cytokine levels suggest a role for new immunomodulatory treatments to prevent disease progression in COME, regardless of atopy.     

Microarray Analysis of Gene Expression Alteration in Human Middle Ear Epithelial Cells Induced by Asian Sand Dust

Objectives

The primary aim of this study is to evaluate the gene expression profile of Asian sand dust (ASD)-treated human middle ear epithelial cell (HMEEC) using microarray analysis.

Methods

The HMEEC was treated with ASD (400 µg/mL) and total RNA was extracted for microarray analysis. Molecular pathways among differentially expressed genes were further analyzed. For selected genes, the changes in gene expression were confirmed by real-time polymerase chain reaction.

Results

A total of 1,274 genes were differentially expressed by ASD. Among them, 1,138 genes were 2 folds up-regulated, whereas 136 genes were 2 folds down-regulated. Up-regulated genes were mainly involved in cellular processes, including apoptosis, cell differentiation, and cell proliferation. Down-regulated genes affected cellular processes, including apoptosis, cell cycle, cell differentiation, and cell proliferation. The 10 genes including ADM, CCL5, EDN1, EGR1, FOS, GHRL, JUN, SOCS3, TNF, and TNFSF10 were identified as main modulators in up-regulated genes. A total of 11 genes including CSF3, DKK1, FOSL1, FST, TERT, MMP13, PTHLH, SPRY2, TGFBR2, THBS1, and TIMP1 acted as main components of pathway associated with 2-fold down regulated genes.

Conclusion

We identified the differentially expressed genes in ASD-treated HMEEC. Our work indicates that air pollutant like ASD, may play an important role in the pathogenesis of otitis media.     

中耳炎手术中面神经定位和辨认的临床研究

目的探讨中耳炎手术中面神经的定位和辨认。方法回顾性分析2008年1月～2010年12月185例行开放式乳突根治术或加鼓室成形术的慢性化脓性中耳炎及胆脂瘤中耳炎患者的手术资料,对术中面神经探查定位及辨认方法进行分析总结。结果①185例中,面神经探查发现58例面神经裸露;②面神经鼓室段定位标志为匙突、齿突、砧骨短突,185例中33例匙突消失,25例齿突遭到破坏,19例砧骨短突破坏或移位;乳突段定位标志为水平半规管、二腹肌脊,185例中12例水平半规管遭破坏,14例二腹肌脊被破坏;33例鼓索神经变异;③面神经与肉芽组织的关系为肉芽组织覆盖于神经表面78例,肉芽包裹神经47例,肉芽组织来自于面神经本身24例。结论中耳炎手术中面神经的定位主要根据相对固定的砧骨、水平半规管、匙突等结构,当这些结构遭破坏或观察不清时,应联合多个标志综合判断,提高面神经定位的成功率。     

氮气导入中耳腔治疗分泌性中耳炎疗效观察

目的 将氮气(N2)导入分泌性中耳炎患者的中耳腔，希望以此产生并维持长时间的中耳腔正压，达到治疗分泌性中耳炎的目的。方法 用咽鼓管导管吹张法将N2导入20耳分泌性中耳炎患者的中耳腔，用声导抗仪动态观察中耳腔压力的变化，并随访观察患者的症状、体征的变化，判断疗效；将结果与行空气吹张的另20耳分泌性中耳炎作对照组比较。结果 中耳腔在导入N2后能维持较长时间的正压和压力升高。但两组疗效的差别无统计学意义。结论 在治疗分泌性中耳炎时，N2导人中耳腔并未比一般的咽鼓管吹张(空气)显示出更好的疗效。     

Deep Learning Techniques for Ear Diseases Based on Segmentation of the Normal Tympanic Membrane

ObjectivesOtitis media is a common infection worldwide. Owing to the limited number of ear specialists and rapid development of telemedicine, several trials have been conducted to develop novel diagnostic strategies to improve the diagnostic accuracy and screening of patients with otologic diseases based on abnormal otoscopic findings. Although these strategies have demonstrated high diagnostic accuracy for the tympanic membrane (TM), the insufficient explainability of these techniques limits their deployment in clinical practice.MethodsWe used a deep convolutional neural network (CNN) model based on the segmentation of a normal TM into five substructures (malleus, umbo, cone of light, pars flaccida, and annulus) to identify abnormalities in otoscopic ear images. The mask R-CNN algorithm learned the labeled images. Subsequently, we evaluated the diagnostic performance of combinations of the five substructures using a three-layer fully connected neural network to determine whether ear disease was present.ResultsWe obtained the receiver operating characteristic (ROC) curve of the optimal conditions for the presence or absence of eardrum diseases according to each substructure separately or combinations of substructures. The highest area under the curve (0.911) was found for a combination of the malleus, cone of light, and umbo, compared with the corresponding areas under the curve of 0.737–0.873 for each substructure. Thus, an algorithm using these five important normal anatomical structures could prove to be explainable and effective in screening abnormal TMs.ConclusionThis automated algorithm can improve diagnostic accuracy by discriminating between normal and abnormal TMs and can facilitate appropriate and timely referral consultations to improve patients’ quality of life in the context of primary care.     

Toll-like Receptors 2 and 4 and Their Mutations in Patients with Otitis Media and Middle Ear Effusion

Objectives

Toll-like receptors (TLRs) detect microbial infections and they can directly induce innate host defense responses. TLR 2 has been shown to be primarily involved in the recognition of peptidoglycans and lipoteichoic acid of gram positive bacteria. TLR 4 recognizes lipopolysaccharides and lipoteichoic acids from both gram-negative and gram-positive bacteria. Both mutations lead a reduced capacity to elicit inflammation and they increase the risk for gram-positive and negative infections. This study was performed to investigate the expressions of TLR 2 and 4 and their mutations in patients suffering with otitis media and middle ear effusion.

Methods

Middle ear fluid samples were collected from 40 otitis media effusion (OME) patients who had ventilating tubesinserted. Bacteria in the effusion fluid were detected by standard bacterial culture. The secreted IgG, IgA and IgM were measured by Enzyme-linked immunosorbent assay. TLR 2 and 4 were assessed by performing RT-PCR. The genomic DNA from each patient was isolated from the middle ear fluid samples that were collected from 60 OME patients, and the presence of mutations was determined by performing restriction digestion and DNA sequencing analysis.

Results

Among the 40 middle ear fluid samples, bacteria were detected in 13 middle ear fluid samples. The amounts of IgM, IgA, and IgG were 151.20±60.94 ng/mL, 21.59±7.96 ng/mL and 11.55±16.98 ng/mL, respectively. TLR 2 and 4 were expressed in the middle ear fluid and the expression of TLR 2 was higher than that of TLR 4. However, there was no correlation between the expressions of TLR 2 and 4, and the concentration of immunoglobulin or the presence of bacteria (P>0.05). There ware no mutations of TLR 2 (Arg753Gln, Arg677Trp) and TLR 4 (Asp299Gly, Thr399Ile).

Conclusion

TLR 2 and 4 were expressed in all the middle ear fluid samples of OME, but the mutations of TLR 2 and 4 were not detected. TLR 2 and 4 may play a vital role in the immunological responses of patients with OME.     

Influence of Vibration to the Neck,Trunk and Lower Extremity Muscles on Equilibrium in Normal Subjects and Patients with Unilateral Labyrinthine Dysfunction

To investigate the role of proprioceptors of different skeletal muscles in postural control, in normal subjects and patients with unilateral labyrinthine dysfunction (ULD), the effect of vibration on these muscles was studied by postulography. The subjects comprised 59 normal subjects and 12 patients with ULD due to resection of acoustic tumours. Sagittal body sway was observed during vibration to the triceps surae, tibialis anterior and upper dorsal neck muscles. No significant change in sway was observed in the frontal plane in normal subjects. Significant differences between normal subjects and patients were found on stimulation of the muscle groups of triceps surae and biceps femoris during vibration. In patients with ULD, vibration to the dorsal neck muscles caused a deviation towards the diseased side. It can be speculated that the upper dorsal neck muscle plays an important role in maintaining the body balance in the frontal plane in patients with ULD. On the other hand, the lower extremity muscles, especially the muscles on the dorsal side of the body, play a significant role in adjusting the standing posture in the sagittal plane.     

钠离子浓度变化对大鼠中耳液体吸收功能影响的研究

目的 探讨健康大鼠中耳黏膜中液体吸收速度和钠离子浓度的相关性.方法 24只大鼠分成Ⅰ、Ⅱ、Ⅲ、Ⅳ组,每组6只,全身麻醉后分别在各组实验耳注入10、40、80、140 mM的NaC1溶液,对照耳注入140 mMNaC1溶液.30分钟后,中耳腔液体的体积开始发生稳定变化,监测液体体积的变化,描记体积和时间变化曲线,通过线性回归计算液体吸收速率(K);吸收速率比(KR=K试验/K对照)定义为实验耳的吸收速率(K试验)与对照耳的吸收速率(K对照)的比值.结果 Ⅰ、Ⅱ、Ⅲ、Ⅳ组的KR值分别为:0.5455±0.0685、0.6353±0.0579、0.7575±0.0611、0.9774±0.0585,差异有显著统计学意义(P＜0.001);通过线性回归分析,KR值和钠离子浓度呈正相关性(r=0.9424,P＜0.001).结论 本实验证实了活体动物中耳黏膜具有吸收功能,其吸收速度与钠离子的浓度呈正相关.     

儿童与成人分泌性中耳炎临床特征比较

目的 探讨儿童与成人分泌性中耳炎的临床特征的异同.方法 回顾性分析我科2004年3月～2006年3月诊治的84例(104耳)儿童和41例(53耳)成人分泌性中耳炎患者的临床资料,比较其病因、病程、首发症状和听力受损特征的异同.结果 儿童分泌性中耳炎患者平均病程较成人短,病因以腺样体肥大和上呼吸道感染为主,首诊原因多为耳痛,其次为听力下降;成人患者病程较长,病因以慢性鼻窦炎鼻息肉和鼻咽部新生物为主,首诊原因多为听力下降,其次为耳闷.儿童与成人患者都可出现骨导听阈提高,以2、4、8 kHz为主.结论 儿童与成人分泌性中耳炎患者在病因、病程及首发症状等方面有所不同,且儿童患者可造成言语语言发育迟缓,应及早诊治.     

The Evaluation of Oxidative Stress in the Serum and Tissue Specimens of Patients With Chronic Otitis Media

Objectives

To underline the effect of oxidative stress in chronic otitis media with and without cholesteatoma and to compare the oxidative stress values in the serum and tissue specimens in these two forms.

Methods

The study included a total of 75 individuals, 35 cases with chronic otitis media (COM; 16 females and 19 males) and a healthy control group of 40 cases (20 females and 20 males). The COM patient group was comprised of 18 patients with cholesteatoma and 17 patients without cholesteatoma. All patients underwent mastoidectomy. Serum specimens were taken prior to surgery and diseased tissue specimens from the ear were obtained during surgery from all patients. Only serum specimens were taken from the healthy control cases. The malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GHPx) were measured in the serum and tissue samples of the patient group and in the serum specimens of the control group.

Results

The age ranged from 14 to 48 years in the patient group (mean age, 20.4±12.2 years) and from 19 to 40 years in the control group (mean age, 26.4±4.64 years). When the serum values of all COM patients were compared with those of the control group, in the patient group MDA, which reflects lipid peroxidation, was found to be significantly higher (P<0.01) whereas the antioxidant enzymes SOD, CAT, and GHPx were found to be significantly lower (P<0.01). When the serum and tissue MDA, SOD, CAT, and GHPx values in patients with and without cholesteatoma were compared, no significant difference was found these parameters (P>0.01).

Conclusion

Although oxidative stress plays a role in the pathogenesis of COM with or without cholesteatoma, it may not reflect the severity of the disease. In patients with COM, the evaluation of only serum oxidative stress values without tissue evaluation may be sufficient for assessing oxidative stress.     

In VitroStreptococcus pneumoniae Biofilm Formation and In Vivo Middle Ear Mucosal Biofilm in a Rat Model of Acute Otitis Induced by S. pneumoniae

Objectives

Streptococcus pneumoniae is one of the most common pathogens of otitis media (OM) that exists in biofilm, which enhances the resistance of bacteria against antibiotic killing and diagnosis, compared to the free-floating (planktonic) form. This study evaluated biofilm formation by S. pneumoniae on an abiotic surface and in the middle ear cavity in a rat model of OM.

Methods

In vitro biofilm formation was evaluated by inoculation of a 1:100 diluted S. pneumoniae cell suspension in a 96-well microplate. Adherent cells were quantified spectrophotometrically following staining with crystal violet by measurement of optical density at 570 nm. The ultrastructure of pneumococcal biofilm was assessed by scanning electron microscopy (SEM). For in vitro biofilm study, S. pneumoniae cell suspensions containing 1×10⁷ colony forming units were injected through transtympanic membrane into the middle ear cavity of Sprague Dawley rats. The ultrastructure of middle ear mucus was observed by SEM 1 and 2 weeks post-inoculation.

Results

The in vitro study revealed robust biofilm formation by S. pneumoniae after 12-18 hours of incubation in high glucose medium, independent of exogenously supplied competence stimulating peptide and medium replacement. Adherent cells formed three-dimensional structures approximately 20-30 µm thick. The in vivo study revealed that ciliated epithelium was relatively resistant to biofilm formation and that biofilm formation occurred mainly on non-ciliated epithelium of the middle ear cavity. One week after inoculation, biofilm formation was high in 50% of the treated rats and low in 25% of the rats. After 2 weeks, biofilm formation was high and low in 25% and 37.5% of rats, respectively.

Conclusion

The results imply that glucose level is important for the S. pneumoniae biofilm formation and S. pneumoniae biofilm formation may play important role in the pathophysiology of OM.     

咽鼓管吹张器治疗儿童分泌性中耳炎的Meta分析

目的 通过Meta分析系统评价咽鼓管吹张器(Autoinflation)在儿童慢性分泌性中耳炎(OME)临床疗效、依从性、安全性.方法 检索PubMed、OVID、Embase、Cochrane Library、Proquest、Web of Science、中国生物医学文献数据库、万方、CNKI数据库(自建库至202...     

耳内窥镜在中耳疾病诊治中的应用

目的 耳内窥镜在中耳疾病诊治中的作用。方法 使用内窥镜系统对300例(340耳)耳病患者进行了诊治,并对其中57例(68耳)分泌性中耳炎进行了穿刺抽液注药或置管治疗,42例(50耳)慢性化脓性中耳炎进行了吸脓、去肉芽及胆脂瘤治疗,15例(17耳)胆脂瘤中耳炎术后清理术腔病变,以及21例(21耳)干性鼓膜穿孔进行了鼓膜修补术。结果 发现内窥镜的应用使中耳疾病的诊断率从常规检查的93.5％提高到100％,内窥镜下对分泌性中耳炎、慢性化脓性中耳炎、胆脂瘤中耳炎术后复发及干性穿孔的鼓膜修补治愈率分别为75％、88％、100％及95.2％。结论 耳内窥镜具有图像清晰、操作简便、不同视角、损伤小等优点,有利中耳疾病的诊治,应积极推广。     

Long-term Changes of Hearing Thresholds and Eustachian Tube Function After Balloon Dilation of the Eustachian Tube in Patients With Chronic Otitis Media

ObjectivesThis study aimed to evaluate long-term changes after balloon dilation of the Eustachian tube (BDET) in chronic otitis media (COM) patients with Eustachian tube (ET) dysfunction that persisted after tympanomastoidectomy (TM).MethodsWe retrospectively reviewed the medical records of consecutive patients who were diagnosed with COM and ET dysfunction and underwent TM at our tertiary hospital from 2016 to 2017. The tympanic membrane status, the presence of a ventilation tube, ability to perform the Valsalva maneuver, and audiologic changes after dilation of the ET were analyzed.ResultsThis study included 20 patients (with 21 ears) who underwent TM but could not perform the Valsalva maneuver, showed a persistent air-bone gap, and eventually underwent BDET (male:female, 8:13; right:left, 11:10). Four ears showed perforation of the tympanic membrane after TM. Among the remaining 17 ears, 15 ears underwent ventilation tube insertion before BDET, while two ears underwent ventilation tube insertion and BDET simultaneously. Although none of the patients were capable of the Valsalva maneuver before BDET, 13 (62%) were able to perform the Valsalva maneuver successfully after BDET. When evaluating the tympanic membrane status at the latest follow-up, ventilation tubes were still present in eight ears. In the other 13 ears, intact tympanic membranes were present in nine out of 11 ears n the successful Valsalva group, whereas none of them were intact in the unsuccessful Valsalva group (P=0.014). The successful Valsalva group after BDET showed an improved air-bone gap of 8.9±12.4 dB, while the unsuccessful Valsalva group showed an aggravated air-bone gap of 3.8±11.8 dB at 1 year after BDET; this difference was statistically significant (P=0.031).ConclusionThe Valsalva maneuver could be performed successfully after BDET by 62% of patients with COM and ET dysfunction. BDET is helpful for successful hearing improvement and improved tympanic aeration in COM patients with ET dysfunction.     

外、中耳术后残腔异物1例

1 临床资料 患者,男性,25岁,因助听器耳样及耳障嵌顿于右外耳道半日,于2010年3月19日就诊.患者右耳选配助听器,取耳样时将其折断,剩余耳样及耳障嵌顿于耳道内术后残腔,因外耳道口较狭窄不能取出就诊时右耳疼痛,堵塞感,无流水.     

Relationship Between Severity of Middle Ear Mucosal Lesion and Middle Ear Pneumatic Space Volume in Patients with Otitis Media with Effusion

If we assume that the state of suppression of pneumatic cells is the result of suppression of pneumatic cell growth by inflammatory stimulation in the middle ear pneumatic space, it is possible to improve the state of suppression by performing sufficient treatment during the growth period of the pneumatic cells. We indwelt a tympanic membrane ventilation tube (hereinafter referred to as tube) for treatment of otitis media with effusion (OME) in child patients aged 3-13 years and investigated the following points: i) relationship between the severity of inflammation of the lamina propria of middle ear mucosal specimens (hereinafter referred to as lamina propria) collected at the time of tube indwelling and the degree of growth of the pneumatic space; and ii) changes in the pneumatic space associated with treatment by tube indwelling, which was studied by comparing the above-described mucosal severity with the pneumatic space area of 2 years after tube indwelling, and with increase in the pneumatic space volume measured periodically after tube indwelling. The results indicated that mastoid cell growth suppression is higher in patients with a higher degree of inflammatory changes in the lamina propria. In association with treatment by tube indwelling, effusion accumulated in the pneumatic space and mucosal swelling disappeared early after the treatment, or 2 months of tube indwelling. After that, in patients with severe mucosal lesion, a long time, 1.5-2 years, was found to be required for repneumatization accompanying regrowth of the temporal bone. We confirmed that the severity of inflammation of the lamina propria is deeply involved in the growth and repneumatization of the pneumatic cells.     

Expression of EGFR and Microvessel Density in Middle Ear Cholesteatoma

Objectives

Cholesteatoma destructs bony tissue by the interactions between hyperproliferative epithelial cells and subepithelial inflammatory cells. The aim of this study was to evaluate the expression of epidermal growth factor receptor (EGFR) and microvessel density (MVD) in middle ear cholesteatoma tissue in an effort to determine the relationship between expression of EGFR and neovascularization.

Methods

We evaluated the expression of EGFR and MVD by immunohistochemical staining for CD31 and Factor VIII in 32 cholesteatoma tissue samples and 7 normal postauricular skin samples. We also analyzed the correlation between EGFR expression and MVD.

Results

The expression of EGFR was higher in cholesteatoma than in postauricular skin, but the difference was not statistically significant. EGFR was more highly expressed in the suprabasal layer than in the basal layer. Using CD31 and Factor VIII, we analyzed the MVD and found that it was significantly higher in cholesteatoma than in postauricular skin, and significantly correlated with the expression of EGFR.

Conclusion

Our results suggest that overexpression of EGFR and neovascularization are correlated with the growth of cholesteatoma.     

低龄及学龄儿童鼓膜置管手术预后及其影响因素分析

目的　探讨低龄和学龄儿童鼓膜置管术的预后及其影响因素。方法　2012年1～12月间因分泌性中耳炎于我科行鼓膜置管术的100例儿童患者病例,对其进行2年的术后随访,依据年龄将病例分成两组,低龄组和学龄组,比较两组间术前纯音测听平均听阈、术后（2周、0.5年、1年和2年）纯音测听平均听阈、手术方式、置管脱出时间、鼓膜愈合情况、OME复发和二次置管情况。结果　两组术前纯音测听平均听阈比较,差异无统计学意义;两组术前与术后各阶段纯音测听平均听阈比较,差异有统计学意义;两组手术方式比较,差异有统计学意义（χ2=-2.067,P =0.039）;两组置管脱出或取出时间比较,差异有统计学意义（Z=-0.045,P =0.952）;两组OME复发比较,差异无统计学意义;两组二次置管情况比较,差异有统计学意义（χ2=-2.254,P =0.012）。鼓膜出现钙斑者5例,残留穿孔者2例,1例行鼓膜修补术;术后出现耳漏者7例,均治愈。手术方式及置管时间与二次置管之间具有显著相关性。结论　低龄组二次置管情况低于学龄组,可能与同期行腺样体切除术有关。