氨基糖苷类药物耳毒性机制及耳保护策略研究进展

氨基糖苷类药物被认为是损伤内耳、导致听力损失的最常见药物之一,其导致的耳聋对于具有遗传易感性的患者往往是极重度且不可逆的.近些年,科学家对耳毒性过程以及如何在细胞水平上进行防护的研究进一步深入,并提出了一些耳保护策略与氨基糖苷类药物导致的耳毒性副作用相抗衡.本文对氨基糖苷类药物耳毒性的作用机制、影响因素以及当前的耳保护...     

耳硬化症的基因学研究进展

耳硬化症（otosclerosis）是骨迷路致密板层骨因局灶性吸收并被富含血管和细胞的海绵状新骨所替代，继而血管减少、骨质沉着，形成骨质硬化病灶而产生的疾病。耳硬化症是原发性骨迷路的病变，多发生在前庭窗前部。病变累及环韧带与镫骨时，可导致镫骨同定，听力下降，尤以语频区听力为甚。临床表现为慢性进行性双耳听力下降．可伴耳呜及眩晕。如病灶仅局限于骨迷路的骨壁内而未侵及传导和感音结构，可无任何症状，只是在尸检作颢骨组织切片时方被发现，这种不引起临床症状的骨迷路组织学的病变，称为“组织学耳硬化症”（histological otosclerosis）：若病变向骨壁范围之外扩展，侵及环韧带，使镫骨活动受限或固定，出现进行性传音功能障碍者，称为“临床耳硬化症”（clinical otosclerosis），也称“镫骨性耳硬化症”（stapedial otosclerosis）；若病变发生在耳蜗区或甚至侵袭内耳道，引起耳蜗损害或听神经变性，临床表现为感音神经性聋，称“耳蜗性耳硬化症”（cochlear otosclerosis）.     

耳硬化症的病因及治疗

耳硬化症（otosclerosis）又名耳海绵化症（otospongio—sis）,是一种以原发性迷路包囊骨海绵样变性为病理特征的内耳疾病。其颞骨病理特征为骨迷路包囊灶性骨质吸收,髓腔扩大,血管增多,呈海绵样变,破骨、成骨现象可同时存在。临床耳硬化症的发病率随种族和地区不同而有所不同。白种人的发病率最高,为0．3％～0．5％,     

持续麻疹病毒感染：——耳硬化症可能的病因

文章介绍了麻疹病毒与耳硬化症之间的关系，认为麻疹病毒应该考虑为自发性耳硬化症的可能病因。     

鼓室硬化症的病因与发病机制相关研究进展[综述]

鼓室硬化症是复发性慢性中耳感染的常见后遗症,其特点是进行性玻璃样变性、鼓膜和中耳腔黏膜下层钙化沉积物的积累。相对于钙化的数量及其对听骨链运动的干扰,患者会出现不同程度的传导性听力损失。尽管目前鼓室硬化症的病因与发病机制尚未完全阐明,但当前普遍认为它是不可逆的。手术治疗是迄今为止恢复听力最有效的方法,却不能阻止其病理变化的发生发展,因此明确本病的病因显得尤为重要。本文就鼓室硬化症的病因与发病机制的最新研究进展做一综述,以期对临床工作提供帮助。     

影像学检查在耳硬化症诊治中的应用及研究进展

耳硬化症是一种表现为鼓膜完整的传导性或混合性听力下降的疾病。耳硬化症的诊断主要根据患者病史和准确的听力学检查,影像学起到辅助作用。但近年来随着影像学技术的发展,影像学检查在耳硬化症的诊疗过程中愈加重要,从术前诊断、鉴别诊断、术前评估手术难度、预测并发症,到术后分析并发症、评估手术疗效等都起到非常重要的作用。本文通过查阅相关文献资料,对耳硬化症影像学的研究进展进行阐述。     

自发性耳声发射的研究进展

耳声发射 (ｏｔｏａｃｏｕｓｔｉｃｅｍｉｓｓｉｏｎ ,ＯＡＥ)是由耳蜗外毛细胞的主动活动产生的、可在外耳道被检测到的声能信号。根据诱发方式的不同 ,将记录到的ＯＡＥ分为诱发性耳声发射 (ｅ ｖｏｋｅｄｏｔｏａｃｏｕｓｔｉｃｅｍｉｓｓｉｏｎｓ ,ＥＯＡＥ)和自发性耳声发射 (ｓｐｏｎｔａ ｎｅｏｕｓｏｔｏａｃｏｕｓｔｉｃｅｍｉｓｓｉｏｎ ,ＳＯＡＥ)两大类[1] 。ＳＯＡＥ是在安静、无外界声刺激的情况下 ,在外耳道检测到的类似纯音的、低强度的窄带声信号[1～ 4 ] 。这种在不施加任何声刺激的情况下 ,耳蜗能够自行发出具有一定特征…     

镫骨手术治疗耳硬化症的术式选择

目的：探讨镫骨手术治疗耳硬化症的最佳术式,提高治疗效果。方法：总结了耳硬化症的镫骨手术７１例（耳）体会。其中镫骨提高术３１例,镫骨部分切除术３４例,镫骨全切除术６例。结果：术后随访,镫骨提高术和镫骨部分切除术具有同样稳定的近、远期听力效果。结论：认为镫骨提高术操作简便易行,前庭反应轻,应作为镫骨手术首先考虑的术式,即使镫骨撼动时足弓折断,也不影响后续手术的进行。     

耳蜗性耳硬化症3例报告及文献复习

目的：探讨耳蜗性耳硬化症的临床特点。方法：结合文献复习,报告3例2007年3月-2008年10月诊治的经高分辨颞骨CT确认的耳蜗性耳硬化症患者。结果：3例以反复发作性眩晕或（和）平衡障碍为首要主诉,同时有进行性听力下降病史。2例（各1耳）为单纯感音神经性聋,考虑为“纯”耳蜗性耳硬化症,其余为伴不同程度骨导下降的混合性聋。高分辨颞骨CT的特点：耳蜗、前庭、半规管及内耳道等部位可见低密度区,耳蜗区呈现“晕影”征或“双环”征,密度有不均。结论：对不能解释原因的感音神经性聋、存在前庭症状的混合性聋并呈进行性听力下降的慢性病史者应考虑耳蜗性耳硬化症的可能,CT对耳蜗性耳硬化症的临床诊断有重要价值。     

中耳共振频率对耳硬化症的诊断作用

目的探讨中耳共振频率对耳硬化症的诊断作用。方法对112例听力正常人、91例耳硬化症患者进行中耳分析,纯音听阈,耳声发射及颞骨CT测试,比较226Hz鼓室图与中耳共振频率及CT检查对耳硬化症的诊断价值。结果正常对照组226Hz鼓室图的声导纳范围为0.45±0.28mmho,耳硬化组226Hz鼓室图声导纳值为0.54±0.47mmho,226Hz鼓室图两组比较,差异无统计学意义。中耳共振频率正常对照组为957±220Hz,耳硬化组为1182±318Hz,较正常组高,两组比较差异有统计学意义。共振频率与226Hz鼓室图比较,对耳硬化症诊断的(Receiver operating characteristic curve)ROC曲线下面积更大。226Hz鼓室图、中耳共振频率、颞骨CT对于耳硬化症诊断的敏感度分别为42.86%,71.4%,62.63%。结论与226Hz鼓室图及颞骨CT相比,中耳共振频率对耳硬化症诊断价值更高。     

Current aspects of etiology, diagnosis and therapy of otosclerosis

The presented article shows the current scientific concept including diagnostics and therapy of otosclerosis with an emphasis on surgical treatment options. The three main proposed causes for otosclerosis are viral and hormonal origin as well as a genetic predisposition. In 25 to 50% a familiar accumulation can be seen. Usually patients become aware of clinical problems by a progressive middle ear hearing loss in the young adulthood. In up to 80% of cases both ear become affected during lifetime. Surgical options of therapy are the stapedotomy, stapedectomy and the laser-assisted stapedotomy. In every case the alternative use of a hearing aid must be offered during the consultation. Typical surgical complications are rare but can be persistent vertigo, secondary facial palsy and a sensorineural hearing loss up to complete single-sided deafness in up to 1% of the cases. The most common finding which necessitates stapes revision surgery is the necrosis of the long incus process with dislocation of the stapes piston.     

Current research in otosclerosis

PURPOSE OF REVIEW: The aim of this article is to summarize and put into historical perspective current advances in research in otosclerosis, a disorder of the human temporal bone with a hereditary predisposition that is among the most common causes of acquired hearing loss. RECENT FINDINGS: Genetic studies have revealed that otosclerosis is heterogeneous, with evidence for defects in at least seven genes associated with six distinct chromosomal loci. Measurements of high levels of osteoprotegerin expression in the normal otic capsule and soft tissues of the cochlea provide the first molecular insight as to why the normal otic capsule remodels minimally, if at all. Osteoprotegerin knockout mice provide the best available animal model to date to study abnormal otic capsule remodeling that closely resembles otosclerosis. There is mounting evidence that the measles virus plays an important role in pathogenesis of otosclerosis although the mechanisms by which the virus results in otosclerosis remain unknown. Quantitative measures of angiogenesis can reliably distinguish between clinical and histological otosclerosis. Advances in the emerging field of osteoimmunology will likely impact and benefit from the research in otosclerosis. SUMMARY: Insights into molecular mechanisms that inhibit extensive remodeling in the normal otic capsule, and understanding of how these mechanisms are dysregulated in otosclerosis will allow future design of rational treatment strategies for otosclerosis.     

An overview of the etiology of otosclerosis

Otosclerosis is the primary disease affecting the homeostasis of otic capsule and is among the most common causes of acquired hearing loss. Otosclerosis is considered as a multifactor disease, caused by both genetic and environmental factors. The aim of the present review is to summarize and analyze the bibliographic data, associated with the etiology of the disease. In some cases, the otosclerosis has an autosomal dominant mode of inheritance with incomplete penetrance. Genetic studies reveal the occurrence of at least nine chromosomal loci as candidate genes of the disease. The localized measles virus infection of the otic capsule has been postulated as a possible etiological theory. The role of hormonal factors, immune and bone-remodeling system in the etiopathogenesis of otosclerosis and the association of the disease with the disorders of the connective tissue are the issues of the present study. Despite the extensive research, many etiological factors and theories have been suggested and the process of development of the otosclerosis remains unclear.     

Biochemical studies of otosclerosis

Summary Ossicles and cortical bone from the inner end of the posterior meatal wall were obtained from otosclerotic and non-otosclerotic patients and assayed for hexosamine (an index of total mucopolysaccharide) and for hydroxyproline and proline (an index of collagen content). Ossicles and curettings from various regions of uninvolved temporal bone were similarly assayed. Hexosamine and hexuronic acid (an index of acid mucopolysaccharide) were determined in samples of vein from otosclerotic and non-otosclerotic subjects.No differences were found between otosclerotic and non-otosclerotic individuals with respect to the hexosamine or the hydroxyproline and proline content of ossicles and cortical bone. These results indicate that no quantitative changes in the amount of total mucopolysaccharide or in the fibrillar content of the bone matrix occur as a result of the otosclerotic process. Differences in hexosamine content were observed among samples of bone from various regions of uninvolved temporal bone. Since similar differences were found among samples of bone from otosclerotic patients, the indication is that these differences are inherent. There was no correlation between the inherent regional variations in the mucopolysaccharide content of the ground substance of the otic capsule and the frequency of occurrence of otosclerotic foci.No differences were observed in either the hexosamine or the hexuronic acid content of vein from otosclerotic and non-otosclerotic subjects.

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Zusammenfassung Teile von Hörknöchelchen und Knochenteilchen vom proximalen Ende der hinteren Gehörgangswand von Patienten mit und ohne Otosklerose wurden auf ihren Gehalt an Hexosamin (als Index für Mucopolysaccharide) und für Hydroxyprolin und Prolin (als Index für Kollagen) untersucht. Ebenso warden Hörknöchelchen und Kürettagen von verschiedenen Bezirken des nicht befallenen Felsenbeines untersucht. An Gefäßwänden von Patienten mit und ohne Otosklerose warden Hexosamin und Hexuronsäure (als Index für saure Mucopolysaccharide) bestimmt.Die Untersuchungen von Gehörknöchelehen und Teilchen der knöchernen Gehörgangswand ergaben keinen unterschiedlichen Gehalt von Hexosamin und Hydroxyprolin und Prolin bei Patienten mit und ohne Otosklerose. Diese Resultate zeigen, daß keine quantitativen Veränderungen der Gesamtmucopolysaccharide oder der fibrillären Bestandteile der Knochengrundsubstanz vorkommen, die als Produkt der Otoskleroseerkrankung angesehen werden können. Dagegen fanden sich Untersehiede im Hexosamingehalt der Proben von verschiedenen Gegenden bei nicht befallenen Felsenbeinen. Weil aber ähnliche Untersehiede auch am Felsenbeinknochen von Otosklerosepatienten gefunden werden, mu\ man annehmen, daß diese Unterschiedlichkeiten normalerweise vorkommen. Auch gab es keine Korrelation zwischen den normalerweise vorkommenden regionalen Schwankungen im Mucopolysaccharidgehalt der Grundsubstanz der Labyrinthkapsel und der Häufigkeit von Otoskleroseherden.Ebenfalls konnten keine Untersehiede im Hexosamingehalt und im Hexuronsäuregehalt von Gefäßwänden bei Otosklerosepatienten und bei Patienten ohne Otosklerose nachgewiesen werden.

     

A Contribution to the pathogenesis of otosclerosis

Summary In a histochemical and electron microscopical study the pathogenesis of Otosclerosis was investigated. The morphological changes in the extra- and intracellular space indicated a complex metabolic disturbance of all tissue components. The observed chondrocytic chondrolysis stressed the role of the cartilage remnants in the otic capsule as an etiological factor. There was morphological evidence of a superimposed enzymatic defect.     

The etiology of otosclerosis: A combination of genes and environment

Otosclerosis is a common form of hearing loss characterized by abnormal bone remodeling in the otic capsule. It is a complex genetic disease, caused by a combination of genetic and environmental factors. During the past decade, several attempts have been made to identify factors for otosclerosis. This review provides an overview of the current understanding of the etiology of otosclerosis and describes the genetic and environmental factors that have been implicated in the disease. Environmental factors include fluoride and viral factors, particularly measles. Genetic association studies for otosclerosis have reported several associations of genetic variants that influence the risk of disease, mainly involving bone remodeling pathways, although their individual risk contributions are small. Rare monogenic forms of otosclerosis also exist, which are caused by a mutation in a single gene leading to a clear familial segregation of the disease. Linkage analysis of large otosclerosis families has led to the identification of seven loci, and recently evidence was found that T cell receptor beta is a gene responsible for familial otosclerosis, suggesting an underlying immunological pathway. However, this might also represent an autoimmune process, a hypothesis that is supported by other data as well. In conclusion, a variety of pathways have been identified to be involved in the development of otosclerosis, showing that distinct mechanisms involving both genetic and environmental risk factors can influence and contribute to a similar disease outcome.