C3H/HeJ mouse model for spontaneous chronic otitis media

OBJECTIVES/HYPOTHESIS: Chronic otitis media is a significant clinical problem. Understanding the mechanisms of chronic otitis media is critical for its control. However, little is known of these processes as a result of lack of animal models of spontaneous otitis media. The C3H/HeJ mouse has a single amino acid substitution in its toll-like receptor 4 (TLR4), making it insensitive to endotoxin. As a result, these mice cannot clear Gram-negative bacteria. The chronically inflamed middle ear in this animal provides us the opportunity to study spontaneous chronic otitis media. STUDY DESIGN AND METHODS: Otoscopy and auditory brain response (ABR) evaluation of C3H/HeJ mice at 3, 5, 7, 9, and 11 months were carried out under sedation. At 12 months of age, mice were killed and histologic analysis of the middle ear, inner ear, and eustachian tube was carried out. RESULTS: Tympanic membrane visualization and ABR thresholds in 7- to 8-month-old C3H/HeJ mice showed that approximately half developed middle and inner ear disease spontaneously. The significant elevation of thresholds suggested a sensorineural component in addition to the conductive loss. Middle and inner ear histology showed some degree of middle and inner ear inflammation in half the mice, paralleling the ABR data. CONCLUSIONS: The histopathologic changes reported here in the C3H/HeJ mouse model of chronic otitis media have been reported in human chronic otitis media. This spontaneous model of chronic otitis media will be valuable for the characterization of middle and inner ear inflammatory disease processes that are induced by middle ear infections.     

豚鼠分泌性中耳炎模型的建立

目的 建立豚鼠分泌性中耳炎的动物模型。方法 20只豚鼠均分为对照组和造模组,造模组将0.1ml灭活的肺炎链球菌悬浮液注入豚鼠的鼓室内,5天后耳内窥镜下观察鼓室积液情况,检测反应阈,了解光镜下咽鼓管的组织形态变化。结果 20耳中有14耳出现鼓室积液,光锥消失。反应阈由14.00±3.08dB提高至45.00±5.67dB,光镜下咽鼓管的黏膜面有无结构的红染物覆盖,杯状细胞增多,胞质及胞核深染。结论 灭活的肺炎链球菌悬浮液注入豚鼠的鼓室内制造豚鼠分泌性中耳炎的动物模型切实可行。     

Repeated Inflation Does Not Prevent Otitis Media With Effusion in a Monkey Model

Objective: Investigate the efficacy of repeated middle ear inflation with an inert gas (argon) for preventing the development of middle ear effusion in monkeys with functional eustachian tube obstruction. Study Design: Prospective controlled trial of daily middle ear inflation with five monkeys assigned to the inflation group and four to the control group. Methods: The right tensor veli palatini muscle of nine monkeys was paralyzed with botulinum toxin. Tympanometry was done before the procedure and then daily for 21 days. Presence and distribution of effusion were assessed before paralysis and on day 15 using magnetic resonance imaging (MRI). In five right ears inflation was done beginning at the first observation of negative middle ear pressure of ≤?200 mm H₂O and repeated on all days with pressures ≤?100 mm H₂O. Four right ears served as uninflated controls. Results: Right middle ear pressure decreased in all animals over the course of the study. Pressure returned to near-ambient levels immediately following the argon inflation but was decreased to control levels at the subsequent observation on the following day. MRI at day 15 documented effusion in all right ears with no quantifiable differences in amount or distribution between ears that were and were not inflated with argon. Conclusions: Repeated inflation with an inert gas does not prevent middle ear effusion in monkeys with functional eustachian tube obstruction.     

management of otitis media with effusion

Otitis media with effusion is one of the most common diseases in children. Its treatment remains controversial. Clinical practice guidelines of OME allow watchful waiting for 3 months before treatment if the child with OME is not at risk for speech/language/or learning problems. Tympanostomy tube insertion is the preferred initial procedure when a child becomes a surgical candidate. Complementary or alternative medicine is not recommended as a treatment for OME. This paper provides a systematic review of management of OME, which we hope will be helpful for clinicians.     

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.     

分泌性中耳炎复发的相关因素分析

目的：探讨分泌性中耳炎（otitis media with effusion,OME）复发相关的影响因素。方法分析经鼓膜切开置管术治疗的255例慢性分泌性中耳炎患者的临床资料,其中取出通气管后一年内复发者85例,未复发者170例。对与分泌性中耳炎复发相关的可能因素包括年龄、性别、病程、吸烟环境、反复呼吸道感染、慢性鼻－鼻窦炎、鼻腔结构异常、腺样体肥大或鼻咽淋巴组织增生、乳突气化情况、既往置管手术史、中耳通气管留置时间等进行单因素分析及多因素 Logistic 回归分析。结果单因素分析发现,年龄、反复呼吸道感染（χ2＝22．546,P＝0．000）、慢性鼻－鼻窦炎（χ2＝5．211,P＝0．023）、腺样体肥大或鼻咽淋巴组织增生（χ2＝10．338,P＝0．002）、乳突气化不良（χ2＝15．196,P＝0．000）、通气管留置时间（3～6月）（χ2＝11．347,P＝0．001）对分泌性中耳炎复发的影响有统计学意义。Logistic回归分析显示,小龄、反复呼吸道感染（P＝0．001,OR＝2．992）、腺样体肥大或鼻咽淋巴组织增生（P＝0．021,OR＝2．198）、乳突气化不良（P＝0．000,OR＝3．433）、通气管留置时间（3～6 m）（P＝0．010,OR＝2．237）5个因素对分泌性中耳炎复发的影响有统计学意义。反复呼吸道感染对学龄前、学龄期儿童和青少年复发性分泌性中耳炎影响有显著意义,腺样体肥大或鼻咽淋巴组织增生对学龄前儿童O ME复发的影响有显著意义（P＜0．05）。结论小龄、反复呼吸道感染、慢性鼻－鼻窦炎、腺样体肥大或鼻咽淋巴组织增生、乳突气化不良、通气管留置时间较短可能是导致分泌性中耳炎复发的主要因素。反复呼吸道感染对学龄前、学龄期儿童和青少年的影响较成人更为显著,腺样体肥大对学龄前儿童的影响最为明显。     

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。     

Effect of Nebulized Bovine Surfactant for Experimental Otitis Media with Effusion

Objectives

In this study, we evaluated the efficacy of nebulized bovine pulmonary surfactant on experimentally induced otitis media with effusion (OME) in guinea pigs.

Methods

Twenty guinea pigs were divided into three groups. Four untreated animals served as normal controls. Experimental OME was established in both ears of the remaining 16 animals by a transbullar injection of 10 µL of Pseudomonas aeruginosa lipopolysaccharide in saline. Thereafter, the guinea pigs received nebulized phosphate buffered saline (n=8) or nebulized bovine pulmonary surfactant (n=8). Nebulization was given daily for 7 days. On day 8, all the animals'' passive opening pressure (POP) of the Eustachian tube was measured and histopathological observations of the bulla were made by light microscopy.

Results

Nebulized bovine pulmonary surfactant significantly reduced the POP compared to that of saline nebulization. The bovine pulmonary surfactant improved the tubal patency and produced less histopathologcally-evident edematous bullar mucosa.

Conclusion

Nebulization of bovine pulmonary surfactant plays an important role in treating otitis media with effusion in guinea pigs. Our results suggest that the chosen nebulized bovine pulmonary surfactant can be of good clinical benefit for treating OME in the future.     

分泌性中耳炎中耳积液免疫复合物和抗核抗体测定

４０例（４５耳）中耳积液分别用聚乙二醇沉淀法测免疫复合物（ＩＣ）和荧光显微镜法检测抗核抗体（ＡＮＡ）。结果显示ＩＣ的Ａ值均大于正常人的血清阈值０．１２，波动范围在０．１２４～０．５１２。ＡＮＡ阳性者３２耳，占７１．１％。可以认为，免疫复合物的沉积损伤中耳粘膜是造成中耳积液的重要致病原因。     

Management for the Children with Otitis Media with Effusion in the Tertiary Hospital

Objectives

Recently, new evidence-based recommendations have been introduced for diagnosing and managing otitis media with effusion (OME) in children. However, there are some difficulties to follow the general guidelines in the tertiary hospitals. The purpose is to evaluate the efficiency of antibiotics or antihistamines for treatment of children with OME in the tertiary hospital with a randomized prospective clinical study.

Methods

Eighty-four children with OME who had been diagnosed in the tertiary hospital were randomized to receive 5 different medications for 2 weeks. We prescribed antibiotics (amoxicillin-clavulanate syrup) in Group I (n=16), antibiotics/steroids (prednisolone) in Group II (n=18), antibiotics/antihistamines (ebastine) in Group III (n=15), antibiotics/steroids/antihistamines in Group IV (n=17), and mucolytics (ivy leaf extract) in Group V (n=17) for control. We followed-up children every 2 weeks and evaluated the state of OME at 3 months.

Results

Thirty six (42.9%) of 84 children were resolved within average 6.9 weeks after the treatments. Thirty-six (42.9%) were treated with ventilation tube insertion and 12 patients (14.3%) were observed. There was no difference in the resolution rates of OME among the five different protocols (P>0.05). There was no difference in the resolution rates among groups who used steroids, antihistamines, steroids and antihistamines, or other medications to manage 42 children with allergies (P>0.05).

Conclusion

In the tertiary hospital, the cure rate of children with OME was not as high as well-known, and antibiotics or anti-allergic medications were not more effective than control. We may, therefore, need any other guidelines which are different from the previous evidence-based recommendations, including early operation in the tertiary hospitals.     

小白鼠实验性分泌性中耳炎粘附分子的表达

目的 研究粘附分子表达与分泌性中耳炎的关系。方法 采用灭活未分类流感嗜血杆菌制备小白鼠分泌性中耳炎模型，了解中耳粘膜的病理改变，检测其对白细胞粘附分子表达的影响。结果 实验组小白鼠粘附分子Mac-1和L-selectin的表达明显增加，伴有相应中耳粘膜病理改变。结论 死亡的细菌可能作为一种抗原，导致中耳粘膜的炎症反应及中耳渗出，粘附分子Mac-1及L-selectin的表达与炎症反应密切相关。     

咽鼓管测压对儿童分泌性中耳炎疗效评估的价值

目的 探讨儿童分泌性中耳炎(otitis media with effusion,OME)治疗前后咽鼓管测压(tubomanometry,TMM)对预测OME预后的价值.方法 66例(98耳)OME患儿(中耳炎组,其中单耳34例,双耳32例)分别在治疗前及正规药物治疗后1月内进行声导抗和TMM测试,记录鼓室导抗图类型及咽鼓管评分(eustachian tube scores,ETS)值,并比较二者之间关系,以单耳患者的正常耳(34耳)作为正常对照组.结果 治疗前,中耳炎组ETS平均值(2.27±1.98分)低于正常对照组(5.14±0.98分)(P＜0.01),鼓室导抗图B型耳的ETS平均值(1.70±1.68分)低于C型耳(3.02±2.11分)(P＜0.01).治疗后中耳炎组ETS平均值(3.62±1.85分)显著高于治疗前(P＜0.05),但治疗后鼓室导抗图B型耳的ETS平均值(3.58±1.69分)与C型耳(3.98±1.45分)差异无统计学意义(P＞0.05),B型耳的ETS提高值(1.84±1.7分)高于C型耳(0.72±0.03分)(P＜0.05).无论B型耳还是C型耳,有效组治疗前后ETS平均值及治疗前后ETS差值均高于无效组(P＜0.01).结论 儿童分泌性中耳炎患耳治疗后ETS值提高,咽鼓管功能改善;治疗前鼓室导抗图B型耳的ETS值较C型耳低,治疗后B型耳的ETS提高值高于C型耳;TMM可为临床评估儿童OME预后提供一定参考.     

儿童与成人慢性化脓性中耳炎听力学分析

目的　探讨儿童组与成人组不同类型慢性化脓性中耳炎 (CSOM)听力损失有何异同。方法　对 70例(85耳 )儿童和 99例 (14 1耳 )成人进行纯音测听检查 ,两组患耳进行比较。结果　两组三个类型CSOM患者纯音测听气导听阈均升高。单纯型CSOM在 1～ 8kHz范围内 ,两组气导检查结果呈现听力损失一致 (P >0 .0 5 )。骨疡型和胆脂瘤型CSOM ,除骨疡型 8kHz外 ,两组患耳各频率听力损失也相同 (P >0 .0 5 )。儿童组单纯型CSOM骨导检查结果基本正常 ,而骨疡型和胆脂瘤型CSOM ,成人组在中高频听力损失比儿童重。结论　虽然儿童CSOM病程短 ,呈现气导检查中频、高频听力损失与成人一样重的趋势 ,但无内耳损害或损害较轻。     

Impact of Sulphurous Water Politzer Inhalation on Audiometric Parameters in Children with Otitis Media with Effusion

Objectives

The positive effects of spa therapy on ear, nose, and throat pathology are known but robust literature in this field, is still lacking. The aim of this study was to assess through a retrospective analysis, the effects on otitis media with effusion of Politzer endotympanic inhalation of sulphurous waters in children aged 5-9 years.

Methods

A cohort of 95 patients was treated with Politzer insufflations of sulphurous water: 58 patients did a cycle consisting of a treatment of 12 days per year for three consecutive years; 37 patients followed the same procedure for 5 years consecutively. The control population was represented by untreated, age-matched children. A standard audiometric test was used before and after each cycle of treatment.

Results

One cycle of Politzer inhalation of sulphur-rich water improved the symptoms. Three cycles definitively stabilized the improvement of hearing function.

Conclusion

Our results show that otitis media with effusion in children can be resolved by an appropriate non-pharmacological treatment of middle ear with sulphur-rich water.     

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...     

鼓室置管治疗儿童分泌性中耳炎疗效观察

目的 探讨鼓室置管治疗儿童分泌性中耳炎(SOM)的疗效和并发症。方法 回顾性分析了我科1997年～2001年经鼓室置管治疗的45例(78耳)儿童SOM的临床资料。结果 45例随访1-2年，85％耳(35例，66耳)听力明显改善，鼓室导抗图恢复成A型。结论 积极改善咽鼓管功能并适当延长留管时间，防止过早脱管对提高儿童SOM的治愈率有着积极的意义。     

口服和鼓室内注射糖皮质激素治疗分泌性中耳炎的疗效观察

目的 探讨口服和鼓室内注射糖皮质激素治疗分泌性中耳炎(otitis media with effusion,OME)的疗效.方法 选择84例病程在8周之内的OME患者(8～56岁)为研究对象,在进行鼓室穿刺抽液及口服抗生素的基础上,随机分成A组,30例34耳,予小剂量短疗程口服泼尼松治疗;B组,30例32耳,予地塞米松鼓室内注射2～4次;C组,24例26耳,口服抗生素,鼓室穿刺抽液.疗程结束后随访3个月.结果　A、B两组分别有70.6%和53.1%的患耳在一周内有不同程度好转.治疗一个月后,A、B、C三组的总有效率分别为88.2%(30/34耳)、90.6%(29/32耳)和69.2%(18/26耳);A组与B组总有效率比较差异无统计学意义(P>0.05),但A、B两组与C组总有效率比较差异有统计学意义(P<0.05).结论 口服或鼓室内注射糖皮质激素均为治疗OME的有效方法.     

慢性化脓性中耳炎活动期鼓室成形术的临床观察

目的探讨慢性化脓性中耳炎活动期鼓室成形术的可行性和疗效。方法对37例单侧慢性化脓性中耳炎活动期患者在恢复咽鼓管功能、清除病变的同时行鼓室成形术,随访观察近期及远期疗效。结果术后1年复查,30例鼓膜形态正常,3例鼓膜再穿孔,4例鼓膜内陷。纯音测听气骨导差(air bone gap,ABG)平均缩小10dB者10例,15~20dB者15例,25~30dB者7例,无变化5例。结论慢性化脓性中耳炎活动期可行鼓室成形术。彻底清除病变,恢复中耳通气功能是手术成功的关键。