中耳胆脂瘤分子生物学研究进展

中耳胆脂瘤的发病机理是一个分子难题，分子生物学的发展把研究带入了一个新的领域，本文介绍了与中耳胆脂瘤发病有关的细胞因子的作用机制及相互关系。但中耳胆脂瘤的发病机制是一复杂的病生理过程，有待进一步发展与中耳胆脂瘤发病有关的因素，指导其预防，诊断与治疗。     

小儿中耳胆脂瘤

本文就小儿中耳胆脂瘤的分类、发病率、病因与发病机理以及诊断、治疗和预后进行了综述。同时阐述了小儿与成人中耳胆脂瘤的异同以及小儿中耳胆脂瘤的临床特点。     

HIF-1α与VEGF在中耳胆脂瘤中的研究进展

中耳胆脂瘤是一种主要由角蛋白碎片和角化鳞状上皮及其周围的结缔组织组成的具有侵袭性的疾病,受很多因素影响,发病机制不明确。随着科学技术的进步,研究学者开始从分子生物学方面研究中耳胆脂瘤的发病机制,其中缺氧诱导因子-1α(HIF-1α)及血管内皮生长因子(VEGF)具有多种生物学功能,在中耳胆脂瘤的发病机制中可能有着重要作用。本文主要综述HIF-1α和VEGF的生物学特性,以及两者在中耳胆脂瘤的增殖、凋亡、免疫反应及侵蚀性生长等方面可能的作用,从而为了解HIF-1α和VEGF在胆脂瘤的发病机制中的作用和中耳胆脂瘤的非手术治疗、药物研发提供可能。     

中耳胆脂瘤动物模型的建立及研究进展

中耳胆脂瘤发病机理至今尚未明确,且目前尚无一种药物能够有效地治疗中耳胆脂瘤。动物模型是研究中耳胆脂瘤的发病机制及防治方法的重要工具。常见的胆脂瘤动物模型建立方法有外耳道结扎方法、咽鼓管封闭方法、中耳化学试剂注射模型、自体皮肤鼓室移植+绿脓杆菌注射模型和活体电穿孔基因转染法等,本文对上述5种胆脂瘤动物模型的建立方法与特征进行综述,以期为研究中耳胆脂瘤的发病机制(内陷囊袋学说、上皮移行学说、基底细胞层过度增生学说)及防治方法提供一个良好的实验参考。     

中耳胆脂瘤药物治疗的实验研究进展

中耳胆脂瘤是因角质化鳞状上皮在中耳堆积,造成周围渐近性损害的一种疾病,为耳鼻咽喉科常见病,会导致患者听力下降、耳流脓甚至严重的颅内外并发症.目前针对中耳胆脂瘤的治疗主要采用外科手术,但存在并发症和术后复发的风险,因此中耳胆脂瘤的药物治疗近年来得到国内外学者的重视.本文就中耳胆脂瘤的发病机制和药物治疗研究进展做一综述.     

中耳胆脂瘤药物治疗的实验研究进展[综述]

中耳胆脂瘤是因角质化鳞状上皮在中耳堆积，造成周围渐近性损害的一种疾病，为耳鼻咽喉科常见病，会导致患者听力下降、耳流脓甚至严重的颅内外并发症。目前针对中耳胆脂瘤的治疗主要采用外科手术，但存在并发症和术后复发的风险，因此中耳胆脂瘤的药物治疗近年来得到国内外学者的重视。本文就中耳胆脂瘤的发病机制和药物治疗研究进展做一综述。     

中耳胆脂瘤的遗传学研究进展

中耳胆脂瘤是一类位于鼓室和/或乳突内的团块,由角化的鳞状上皮细胞、上皮下的结缔组织以及角化碎片构成,伴/不伴炎症反应。临床表现主要为耳流脓和听力下降,当侵袭周围组织结构时则可产生眩晕、周围性面瘫、颅内感染等一系列颅内外并发症,甚至危及生命。手术是目前唯一有效的治疗方式。其病因及发病机制仍未完全清楚。随着全外显子测序等新一代测序技术的发展,中耳胆脂瘤的遗传学研究取得了一些突破性进展。近年来,关于胆脂瘤的家族聚集性、基因突变及其与综合征的关系的相关研究越来越多,本文将对上述内容进行综述,从而为中耳胆脂瘤的非手术治疗、药物研发提供参考。     

缺氧诱导因子-1α在中耳胆脂瘤组织中的表达

目的:探讨缺氧诱导因子- 1α(HIF- 1α)在中耳胆脂瘤发病机制中的作用,检测其在中耳胆脂瘤和外 耳道正常上皮中的表达情况。方法:取31例中耳胆脂瘤和10例外耳道正常上皮标本,用免疫组织化学技术检测 HIF-1α蛋白的表达。结果:在中耳胆脂瘤中HIF-1α的表达较外耳道正常上皮明显增多(P<0.05)。结论:中耳 胆脂瘤中HIF-1α的表达显著升高,推测HIF-1在中耳胆脂瘤的发生、发展过程中具有极其重要的作用,并且缺 氧有可能是中耳胆脂瘤发病机制中的一个诱因。     

中耳胆脂瘤成因的基础研究进展

中耳胆脂瘤发病机理至今尚未十分明确 ,本文就中耳胆脂瘤溶骨机制、胆脂瘤上皮的增殖与凋亡及其细胞遗传学方面的研究进展进行综述     

热休克蛋白70相关蛋白在中耳乳突胆脂瘤中的表达与定位

热休克蛋白 (ｈｅａｔｓｈｏｃｋｐｒｏｔｅｉｎｓ,ＨＳＰ)是生物细胞在受到各种损伤因素刺激时产生的高度保守的蛋白质。大量实验证明ＨＳＰ参与炎症和免疫反应[1 3 ] 。中耳胆脂瘤是中耳的慢性炎症性疾病 ,研究和探讨中耳胆脂瘤ＨＳＰ的表达与定位 ,了解ＨＳＰ在中耳胆脂瘤的病因及发病机理中的作用具有重要意义。本研究主要观察ＨＳＰ70相关蛋白在中耳胆脂瘤中的表达与定位。一、材料与方法1 检测标本 :1 6例中耳乳突胆脂瘤组织从 1 997～ 1 999年的中耳乳突手术中获得 ,4例面部皮肤从面部外伤以及面部美容手术中获得 ,2例外耳道皮肤及…     

分泌性中耳炎中耳积液成分研究进展

分泌性中耳炎(SOM)是指以传导性聋及鼓室积液为主要特征的不伴有急性炎性表现的中耳积液的非化脓性中耳炎。其病因与生理机制复杂,以耳闷、耳鸣、耳痛等耳部症状为主,各年龄段均可发生,而学龄前儿童是高发人群。目前,SOM病因及发病机制尚未完全阐明,对SOM中耳积液的成分分析是研究SOM病因及发病机制的常见方法,也是指导临床治疗的重要途径,本文通过查阅国内外发表的相关文献,对SOM中耳积液的成分研究进展进行比较总结,以提高临床医师对该病的认识。     

中耳胆固醇肉芽肿

目的 探讨中耳胆固醇肉芽肿的病因、发病机制以及治疗方法。方法 回顾性总结分析我院1988年3月～2003年3月经手术和病理证实的70例(耳)中耳胆固醇肉芽肿病人的临床资料。70例(耳)中，术前诊断为胆脂瘤型中耳炎37例，骨疡型中耳炎13例，此二者之中考虑胆固醇肉芽肿者13例；中耳乳突术后感染5例，分泌性中耳炎7例，特发性血鼓室8例，其中考虑可能为胆固醇肉芽肿者2例。所有病人均有不同程度听力下降、耳闭塞感或伴耳鸣，亦可有耳溢液、头痛、头昏及其他症状。70例(耳)均接受手术治疗，依照术前检查，根据病变程度不同而选择不同术式。结果 65例(耳)干耳，随访1年以上无复发。3例(耳)行改良乳突根治加鼓室成形术，术后半年流脓，后改行乳突根治术，术后均干耳；2例(耳)行鼓室探查加鼓窦开放术，术后半年及1年又流脓伴听力下降，后改行改良乳突根治加鼓室成形术，术后干耳。结论 中耳胆固醇肉芽肿的病因主要有：含气腔通气受阻、引流障碍及含气腔出血。中耳胆固醇肉芽肿与特发性血鼓室、分泌性中耳炎及胆脂瘤关系密切。术式的选择应根据病变范围和程度来决定，其原则是彻底清除病变，保持通畅引流。     

中耳胆固醇肉芽肿并发胆脂瘤的回顾性分析

目的 探讨中耳胆固醇肉芽肿并发胆脂瘤的病因、发病机制及二者间的相互关系,并就该病的诊断及治疗方法进行讨论。方法 采用回顾性研究,总结分析我院1988年3月－2000年5月经手术和病理诊断证实的63例中耳胆固醇肉芽肿患者中并发胆脂瘤15例患者的临床资料。结果 15例患者均有较长时间的病史,除不同的程度的听力下降外,皆有耳溢然,其中脓血性及血性耳溢液8例;均有鼓膜穿孔,其中松弛部穿孔10例。11例颞骨CT扫描者均报告为胆脂瘤型中耳炎。15例皆行手术治疗,术中发现胆固醇肉芽肿与胆脂瘤交错存在,胆固醇肉芽肿多好发于鼓窦、上鼓室及乳突腔,6例乳突气化良好者气房内有咖啡色粘液蓄积,并有闪烁发亮的点状胆固醇结晶。12例出现鼓窦扩大、上鼓室外侧壁破坏、听骨链侵蚀、鼓室天盖及面神经水平段暴露等骨质破坏。6例咽鼓管鼓口、15例鼓峡阻塞。所有病例术后均干耳,12例行鼓室成形术者11例术后听力有不同程度的提高。结论 中耳胆固醇肉芽肿与胆脂瘤的病理生理改变有共同之处,即均有通气受阻、引流障碍,二者可能为同一致病因素引起的两个不同且相互作用的病理过程。对慢性中耳炎患者出现不 明原因的血性耳溢液者应想到本病可能,应结合CT、磁共振成像（magnetic resonance imaging,MRI)提高术前诊断率。治疗应根据病变部位、范围和程度不同采取不同的术式,其原则是彻底清除病变、通畅引流。     

中耳胆固醇肉芽肿并发胆脂瘤的回顾性分析

目的探讨中耳胆固醇肉芽肿并发胆脂瘤的病因、发病机制及二者间的相互关系,并就该病的诊断及治疗方法进行讨论.方法采用回顾性研究,总结分析我院1988年3月～2000月5月经手术和病理诊断证实的63例中耳胆固醇肉芽肿患者中并发胆脂瘤15例患者的临床资料.结果15例患者均有较长时间的病史,除不同程度的听力下降外,皆有耳溢液,其中脓血性及血性耳溢液8例;均有鼓膜穿孔,其中松驰部穿孔10例.11例颞骨CT扫描者均报告为胆脂瘤型中耳炎.15例皆行手术治疗,术中发现胆固醇肉芽肿与胆脂瘤交错存在,胆固醇肉芽肿多好发于鼓窦、上鼓室及乳突腔,6例乳突气化良好者气房内有咖啡色粘液蓄积,并有闪烁发亮的点状胆固醇结晶.12例出现鼓窦扩大、上鼓室外侧壁破坏、听骨链侵蚀、鼓室天盖及面神经水平段暴露等骨质破坏.6例咽鼓管鼓口、15例鼓峡阻塞.所有病例术后均干耳,12例行鼓室成形术者11例术后听力有不同程度的提高.结论中耳胆固醇肉芽肿与胆脂瘤的病理生理改变有共同之处,即均有通气受阻、引流障碍,二者可能为同一致病因素引起的两个不同且相互作用的病理过程.对慢性中耳炎患者出现不明原因的血性耳溢液者应想到本病可能,应结合CT、磁共振成像(magneticresonanceimaging,MRI)提高术前诊断率.治疗应根据病变部位、范围和程度不同采取不同的术式,其原则是彻底清除病变、通畅引流.     

A new pathogenesis of mesotympanic (congenital) cholesteatoma

OBJECTIVES: To introduce a new, acquired pathogenetic theory of mesotympanic cholesteatoma behind an intact eardrum in children and to present some doubts on congenital pathogenesis. STUDY DESIGN: Literature review. METHODS: The incidence and origination of mesotympanic cholesteatoma in children were thoroughly analyzed in the world literature and correlated to the histopathological studies on human middle ear epithelia and to epidemiological studies on secretory otitis, tubal occlusion, and acute suppurative otitis media. RESULTS: The new, acquired theory is based on the fact that that the place of origin of the anterosuperior mesotympanic cholesteatoma is the area of the malleus handle and malleus neck, and of the posterosuperior cholesteatoma, the long process of the incus. During the common pathological conditions there is a great risk of retractions and adhesions of the eardrum to these ossicles. After subsequent loosening of the retracted eardrum some cells of the keratinized squamous epithelium may be left behind and become included into the tympanic cavity, eventually causing an inclusion cholesteatoma. Four basic mechanisms of inclusions are proposed and the presence of great dynamics in middle ear disease in children, with high incidence of tubal dysfunction, retractions, secretory otitis, and acute suppurative otitis, is documented, making the acquired pathogenesis probable. The place of origin does not fit with the congenital pathogenesis of epithelial formation localized on the lateral wall of the eustachian tube close to the annulus. The origination around the malleus and incus fits better with the proposed acquired pathogenesis. CONCLUSIONS: There are no definitive proofs for the acquired pathogenesis of the mesotympanic cholesteatoma, nor is there experimental research to prove or disprove it. Mesotympanic cholesteatoma, congenital cholesteatoma, acquired pathogenesis of mesotympanic cholesteatoma, cholesteatoma in children, cholesteatoma behind intact eardrum.     

Management of chronic otitis media in the only hearing ear

OBJECTIVE: Chronic ear surgery is difficult. The management of such a disease either with or without cholesteatoma and in an only hearing ear is particularly challenging. Consequences of disease or unintended outcomes of therapy can both result in patient lifestyle alterations of major proportion. This report offers a diagnostic and treatment plan for chronic otitis media with and without cholesteatoma in the only hearing ear. METHODS: More than 10,000 charts of patients with chronic otitis media were retrospectively reviewed. Twenty-seven charts of patients with chronic otitis media in an only hearing ear who underwent surgical treatment were identified. The patients were followed for an average time of 43 months. RESULTS: Overall, the chronic otitis media was well controlled, and there was no change in the average discrimination or hearing thresholds when comparing preoperative and postoperative results. CONCLUSIONS: Chronic otitis media with and without cholesteatoma in an only hearing ear can be treated successfully with hearing preservation. Canal wall down tympanomastoidectomy is performed in most cases. Manipulation of the ossicular chain is avoided, and cholesteatoma that lies over a potential fistula is exteriorized.     

Epidemiologic patterns in childhood hearing loss: a review

In an attempt to clarify international epidemiologic trends, a review of the published literature pertaining to childhood hearing loss is presented. Inconsistencies of methodology and classification, which complicate the interpretation of data and make difficult the quantification of the influence of genuine population differences, are discussed. Selective review of the literature allows certain crude statements to be made regarding childhood hearing loss. In developed countries, serous otitis media is the most common cause of hearing loss in children, affecting up to two thirds of preschool children. In addition, 1.0-2.0/1000 children have bilateral SNHL of at least 50 dB. In underdeveloped countries, suppurative middle ear disease is common and is still frequently associated with either an intratemporal or intracranial complication. SNHL appears to occur almost twice as often as in developed countries, with a greater proportion being of infectious etiology. In specific populations, the Inuits, Amerindians and Aboriginals, acute and chronic suppurative otitis media are almost endemic, yet both cholesteatoma and serous otitis media are uncommon.     

Effect of bacterial endotoxin and middle ear effusion on ciliary activity: implications for otitis media

OBJECTIVES/HYPOTHESIS: Otitis media with effusion (OME) is the most common cause of childhood deafness. The pathogenesis is not fully understood, especially the reasons for failure of mucociliary clearance of the middle ear. It is not clear whether the cilia function normally in the middle ear and eustachian tube in the chronic phase of otitis media with effusion. However, impaired ciliary function in primary ciliary dyskinesia is known to be frequently associated with the development of otitis media with effusion. We hypothesized that endotoxin or the bacterial products in middle ear fluid in otitis media with effusion would adversely affect ciliary activity, thereby contributing to the pathogenesis of the disease. STUDY DESIGN: Laboratory-based study of human ciliary activity with reference to otitis media with effusion. METHODS: We have studied the activity of human adenoidal cilia under various conditions. Ciliary activity in the presence of Haemophilus influenzae endotoxin additions (at varying concentrations) to cultured adenoidal explants has been measured. In addition, ciliary activity of these explants was also observed after addition of middle ear effusion aspirated from patients. RESULTS: We have shown that endotoxin in concentrations far in excess of those found in the middle ear with chronic otitis media with effusion had no effect on ciliary activity. Furthermore, ciliary activity was completely unaffected by the presence of middle ear effusion. CONCLUSION: There is no evidence that ciliary activity is reduced by the constituents of middle ear fluid in chronic otitis media with effusion.     

Detection of bacterial biofilms in different types of chronic otitis media

Biofilms are organized bacterial communities that may be homogeneous or heterogeneous. They play a significant role in the pathogenesis of chronic nasal sinusitis, chronic tonsillitis, cholesteatomas, and device-related infections. Despite this, few studies have been done that examine the presence of bacterial biofilms in tissues from patients with different types of COM or middle ear cholesteatomas. In the current study, we examined the presence of biofilms in surgical tissue specimens from humans with chronic ear infections using scanning electron microscopy (SEM). We hypothesize that bacterial biofilms present differently in patients with different types of chronic otitis media. Our results provide new insights regarding treatment of chronic otitis media. A prospective study was conducted in which middle ear tissues were obtained from 38 patients who underwent tympanoplasty and/or tympanomastoid surgery due to chronic ear infections. A total of 50 middle and mastoid tissue samples were processed for SEM analysis. In addition, 38 middle ear secretion specimens were obtained for routine bacterial culture analysis. Bacterial biofilms were present in 85 % (11 of 13) of patients with middle ear cholesteatoma, 92 % (12/13) of patients with chronic otitis suppurative media (CSOM), and 16 % of patients (2/12) with tympanic membrane perforation (TMP). Fungal biofilms were found in two cases of cholesteatoma. The positive coincidence rate between bacterial biofilms visualized by SEM and bacteria detected by culture was 82 %. Our findings suggest that bacterial biofilms are very common in CSOM and middle ear cholesteatomas. Positive bacterial cultures imply the presence of biofilm formation in CSOM and cholesteatomas. As such, our results provide new insights regarding treatment of chronic otitis media.