分泌性中耳炎咽鼓管及鼓室黏膜的光镜及电镜观察

目的：探讨分泌性中耳炎的发病原因，为临床治疗提供理论依据。方法：通过微波烧灼双侧咽鼓管口，建立分泌性中耳炎动物模型。光镜观察比较咽鼓管管腔及黏一软骨膜和鼓室黏膜变化。电镜观察咽鼓管鼓室段暗颗粒分泌细胞及其表面活性物质样板层体的变化。结果：各组咽鼓管管腔通畅，咽鼓管黏一软骨膜不易受炎症浸润及负压影响。鼓室黏膜水肿、增生、炎性细胞浸润明显，暗颗粒细胞分泌功能受损，表面活性物质板层体结构明显减少或消失。结论：咽鼓管黏一软骨膜在分泌性中耳炎发病过程中起重要作用。表面活性物质减少与分泌性中耳炎的发生密切相关。     

Histo-morphological changes of eustachian tube of guinea pigs with effusion after being treated by pulmonary surfactant]

OBJECTIVE: To study the effect of pulmonary surfactant on otitis media with effusion in guinea pigs to find a new way to manage otitis media with effusion. METHODS: Nonviable heat-killed pneumococci (HKP) solution was inoculated into the middle ear cavity in guinea pigs via a transeardrum approach to set up a model of otitis media with effusion in guinea pigs. Seven days after being injected with pulmonary surfactant (PS) by transeardrum approach, ABR threshold and histomorphological changes of eustachian tube mucosa of guinea pigs were examined by light microscopy and scanning microscopy. RESULTS: Five days following inoculation of HKB serous effusion were present in the middle ear cavity of guinea pigs, but disappearance of light cone. Response (mean +/- s) threshold raised from (14.0 +/- 3.1) dB to (45.0 +/- 5.7) dB. The eustachian tube mucosa was thickened and lined eosin-stained structureless matter over mucosa, while cilia of eustachian tube mucosa irregularly arranged. Seven days after being treated by PS, serous effusion of tympanum was reduced or disappeared, and response threshold decreased from (45.0 +/- 5.7) dB to (23.5 +/- 6.3) dB. There was significantly difference between them (P < 0.001). Eustachian tube mucosa was thinned, Cilia of eustachian tube mucosa regularly arranged to the nasopharynx. CONCLUSION: Pulmonary surfactant plays a important role in otitis media with effusion of guinea pigs.     

Measurement of mucociliary function of the eustachian tube

Mucociliary function of the eustachian tube was measured with a radioisotopic method; 0.01 mL of a human serum albumin labeled with technetium 99m was instilled into the anterior part of the middle ear cavity either through a perforation or by puncturing the tympanic membrane, and its course was followed by a gamma-camera. In the normal eustachian tube, the velocity of the mucociliary transport was 0.7 to 1.1 mm/min. The mucociliary function was totally absent in chronic otitis media, in untreated secretory otitis media, and in the ear with a moist perforation of the tympanic membrane. The mucociliary transport returned to normal when the ear was clinically healed. It is assumed that the impairment of the mucociliary function of the eustachian tube and middle ear plays an important role in the pathogenesis of secretory otitis media and chronic ear discharge.     

Structural changes in the rat middle ear mucosa due to endotoxin and eustachian tube obstruction

The middle ears of 48 rats were used to examine the effects of endotoxin injection, eustachian tube obstruction or a combination of eustachian tube obstruction and endotoxin injection. Animals were killed after 1, 2, 4, or 12 weeks and the middle ears processed for light and scanning electron microscopy. Compared to the normal middle ear mucosa, the epithelial layer was more pseudostratified, cuboidal or cylindrical after endotoxin injection or obstruction of the eustachian tube. In the early phase, numerous ciliated cells occurred in areas originally almost devoid of these cells. At 3 months, degeneration of ciliated cells was observed. The combination of eustachian tube obstruction and endotoxin injection also induced a more pseudostratified, cuboidal or cylindrical epithelium with an increased number of goblet cells. However, an early decrease occurred in the number of ciliated cells in the tympanic orifice of the eustachian tube. Furthermore, inflammatory cells, mainly PMNs, macrophages and lymphocytes, invaded the subepithelial layer after eustachian tube obstruction and endotoxin injection. These structural changes resulted in an impairment of the mucociliary transport system for clearance of the middle ear cavity. For this reason we believe that both endotoxin and eustachian tube obstruction or dysfunction play an important role in inducing persistent mucosal changes in the middle ear cavity, thereby prolonging otitis media with effusion. Received: 13 February 1998 / Accepted: 4 August 1998     

Experimental otitis media with effusion induced by middle ear effusion.

Experimental otitis media with effusion was induced in chinchillas by middle ear effusion, which was induced by an injection of immune complex into the tympanic cavity. To elucidate the pathogenesis of otitis media with effusion, cytologic and biochemical findings of the effusion and histopathology of the middle ear mucosa of effusion-induced chinchillas were compared with those of experimental otitis media with effusion induced by different procedures; eustachian tube obstruction, intratympanic inoculation of endotoxin, and immune reaction. No significant differences were seen in cytology, biochemistry, and histopathology among OMEs induced by these procedures. However, middle ear effusions, when compared with the corresponding sera, were proven to contain higher amounts of histamine and prostaglandin E2. These findings seem to demonstrate that middle ear effusion containing a large number of inflammatory mediators is essential for induction and prolongation of inflammatory reaction in the middle ear.     

Clinical characteristics of so called eosinophilic otitis media.

OBJECTIVE: Although "eosinophilic otitis media" is not as uncommon a condition as was previously believed, its cause and pathogenesis are not yet fully understood. The purpose of this study was to describe the clinical characteristics in patients with "eosinophilic otitis media" to clarify its pathogenesis. METHODS: Seven adult patients with persistent and intractable otitis media with viscous middle ear effusion containing many eosinophils, who were also under treatment for bronchial asthma, were studied. The following examinations were conducted: nasopharyngeal endoscopy, pure-tone audiometry, eustachian tube function test, temporal bone CT scan, blood analysis, bacterial and fungal culture of middle ear effusion, histological study of the middle ear and nasal specimens, and measurement of eosinophilic cationic protein (ECP) in middle ear effusion. RESULTS: Some patients had persistent perforation with papillomatous granulation tissue arising from the mesotympanic mucosa, and all the patients had nasal polyposis. The pure-tone audiometry showed the mixed-type of hearing loss in all the patients, and the hearing level deteriorated progressively during the course in some patients. The eustachian tube function was not always poor but was patulous in some cases. The most severely diseased areas were in the eustachian tube and mesotympanum by temporal bone CT images. All the seven patients had the high levels of total serum IgE, but the RAST scores were negative in three patients and low grade in three patients. The accumulation of eosinophils was observed in middle ear effusion, middle ear mucosa and nasal polyps, and the eosinophils were highly activated with degranulation. High level of ECP was also recovered from middle ear effusion. CONCLUSIONS: Active eosinophilic inflammation occurs in the entire respiratory tract, including the middle ear in these patients. From our present investigation, we propose the criteria and clinical characteristics of "eosinophilic otitis media".     

Otitis media induced by inoculation of a chemotactic factor.

Phagocytic cells in middle ear effusion obtained from patients with acute or chronic otitis media, have antibacterial activity which is an element of the host defense system. In addition, they modify inflammatory responses as they release degranulated substances, phospholipid-derived substances, and active oxygens. To demonstrate both the direct and indirect biological activities of chemotactic factor through migrating inflammatory phagocytic cells in acute otitis media, a synthetic chemotactic peptide, formyl-methionyl-leucyl-phenylalanine (fmlp), was inoculated into the middle ear of guinea pigs. Fmlp induced severe vascular damage, mucosal edema, and infiltration of phagocytic cells 1 and 3 days after inoculation and interstitial fibrosis and calcification 2 weeks after inoculation. Chemotactic factor in the middle ear cavity caused middle ear tissue damage and may play a role in the development of acute and chronic otitis media.     

中耳炎颞骨咽鼓管峡部粘-软骨膜的组织病理学观察

目的：了解中耳炎性病咽鼓管峡部粘－软骨膜的影响。方法：用光镜对３２耳各型中耳炎颞骨（中耳炎组）与５０耳正常颞骨（正常组）标本连续切片的咽这峡部粘－软骨膜，中耳腔鼓岬粘骨组织病理学比较观察。结果：中耳炎组和正常组颞骨标本咽鼓管峡部均无病理性阻塞；中耳炎组峡部粘－软骨膜厚度测量和病理观察，未见有明显炎症改变，与正常组比较无明显差异；而其中耳腔粘骨膜均明显炎症病变。这种炎症截然不同反应的界限恰好在咽这的     

Presence of an 80 kilodalton protein, cross-reacted with monoclonal antibodies to pulmonary surfactant protein A, in the human middle ear.

We report the presence of a middle ear protein that has the same epitope as human surfactant protein A. Monoclonal antibodies (PC-6 and PE-10) against human pulmonary surfactant protein A stained faint granules of the mucosal epithelial cell cytoplasm in the orifice of the eustachian tube immunohistochemically. These antibodies also reacted with middle ear effusion of patients with otitis media with effusion by dot immunoassay, and recognized an 80 kd protein by Western blot analysis. These findings indicate that a protein immunoreactive with PC-6 and PE-10 occurs in the mucosal epithelial cells of the middle ear, and is also present in middle ear effusion. It is therefore likely that this 80 kd protein might be secreted from the mucosal epithelial cells to the middle ear cavity.     

Effects of human middle ear effusions on the mucociliary system of the tubotympanum in the guinea pig

Effusion fluid resulting from otitis media contains a variety of inflammatory substances. This middle ear effusion (MEE) may be itself affect the mucosa of the tubotympanum and contribute to chronicity of the condition. The present study was designed to elucidate in vitro and in vivo effects of MEEs on the mucosa of the guinea pig tubotympanum. The results obtained demonstrated that the ciliary activity of the eustachian tube was reduced in the presence of human MEEs. This activity decreased to approximately 80% in the presence of serous MEE at 48 h and was 60% after exposure to mucoid MEE. Intratympanic inoculation of human MEEs resulted in accumulation of a serous effusion in the tympanic cavity. Histologic study of the tubotympanum in inoculated animals demonstrated mucociliary dysfunction as well as a general inflammatory process and increased vascular permeability. This damage was more prominent following inoculation with the mucoid MEEs. The ciliary depression and inflammation found in the tubotympanum suggest that the pathologic nature of MEEs may be, at least partially, responsible for the chronicity of otitis media.     

First forty-eight hours of developing otitis media: an experimental study

The early inflammatory changes in the tympanic membrane were explored in 2 rat models. Acute otitis media was induced by instillation of Streptococcus pneumoniae type 3 into the middle ear cavity, and otitis media with effusion was induced by blockage of the eustachian tube. Otomicroscopic examination was performed before the rats were painlessly sacrificed at 3, 6, 9, 12, 18, 24, or 48 hours after initiation of the otitis media conditions. The tympanic membrane was studied by light and electron microscopy. Both acute otitis media and otitis media with effusion caused early inflammatory changes of the tympanic membrane, and the pars flaccida was the portion that reacted first. The inflammatory alterations were most pronounced in the acute otitis media model. The course of inflammation showed a bimodal pattern with an early deposition of a filamentous material with a band pattern, typical of fibrin. Despite a fluid-filled middle ear cavity, the inflammatory changes in the otitis media with effusion model were moderate, as was consistent with the clinical appearance of the tympanic membrane.     

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.     

Free radical production by antibiotic-killed bacteria in the guinea pig middle ear

OBJECTIVES: Oxygen free radicals are implicated in the pathogenesis of otitis media Recent investigations with animal models have demonstrated that free radical-mediated damage of the middle ear mucosa, measured as lipid hydroperoxide, occurs when the middle ear cavity is inoculated with Streptococcus pneumoniae. The present study was conducted to examine the effect of antibiotics on free radical-mediated damage in pneumococcal acute otitis media. STUDY DESIGN: Animal model of acute otitis media. METHODS: Seventy-eight guinea pigs underwent bilateral middle ear inoculation with 100 microl of 1) sterile saline as a control, 2) 50 microg/mL amoxicillin, 3) 10(7) colony forming units (CFU)/mL Streptococcus pneumoniae killed with 50 microg/mL amoxicillin, or 4) 10(7) CFU/mL S. pneumoniae. Animals were killed on postoperative day 1 or 5, and the middle ear mucosa was examined for lipid peroxidation as evidence of free radical damage. RESULTS: Mucosal lipid hydroperoxide was significantly elevated compared with control subjects on day 1 in both the antibiotic-killed S. pneumoniae group and the S. pneumoniae-infected group. On day 5, the S. pneumoniae-infected mucosa had significantly higher lipid hydroperoxide levels compared with the antibiotic-killed group and the control subjects. Histological studies confirmed mucosal edema and the presence of inflammatory cells in the infected groups. CONCLUSIONS: Antibiotic-killed bacteria seem to produce free radical-mediated damage to the middle ear mucosa in the early phase of acute otitis media. The clinical implication of this study is that free radical damage to the middle ear mucosa may occur in otitis media despite appropriate antibiotic therapy.     

Influence of nasal allergic reactions on the clearance of middle ear effusion

In order to investigate the influence of nasal allergic reactions on the clearance of middle ear effusion, an animal model of nasal allergy and otitis media with effusion was produced in the same guinea pigs simultaneously by passive sensitization with serum of homologous animals containing IgE antibodies (for nasal allergy) and by inoculation of immunocomplex into the tympanic cavity (for otitis media with effusion). Usually, middle ear effusion appeared within 2 to 3 days and disappeared within 7 to 9 days after the inoculation of immunocomplex. Three days after the inoculation of immunocomplex, intranasal antigen challenge was performed three times daily and continued until the animals were killed. Disappearance of middle ear effusion appeared to be delayed in animals in which nasal allergic reactions were induced. Middle ear effusion was not found in those ears that were not inoculated with immunocomplex. Findings of the present study indicate that IgE-mediated allergic reactions of the mucous membrane lining the nose, nasopharynx, and eustachian tube constitute a factor indicative of a chronic state of disease, rather than a cause of otitis media with effusion.     

细菌生物膜在急性中耳炎大鼠中耳腔的形成特点及意义

目的 通过观察细菌生物膜在急性中耳炎大鼠中耳腔的形成特点,分析其与急性中耳炎的关系,并探讨该中耳炎模型用于细菌生物膜研究的可行性.方法 30只健康雄性SD大鼠,采用随机数字表法分为实验组(24只)和对照组(6只).麻醉后将50μl肺炎链球菌悬液[1×108菌落形成单位(colony forming unit,CFU)/...     

Patulous eustachian tube following otitis media

Loss of weight, dehydration, pregnancy, fatigue, and otitis media are among the factors proposed as causes of a patulous eustachian tube, but true details remain obscure. We studied patients who developed a patulous eustachian tube following otitis media and discuss the relationship between these 2 conditions. Subjects were 12 patients diagnosed with otitis media at our department who later developed a patulous eustachian tube. The initial middle ear disease progressed from acute otitis media to otitis media with effusion in 2, acute otitis media in or acute mastoiditis in 1 each, and otitis media with effusion in the remaining 8 patients. Seven patients evidenced a low body mass index (BMI), weight loss, and underlying disease, but 5 with a patulous eustachian tube following otitis media did not. We retrospectively analyzed 119 patients diagnosed with a patulous eustachian tube in our department for whether they had been diagnosed by an ENT physician as having otitis media, i.e., acute otitis media or otitis media with effusion. Some 42 (35.3%) had a history of otitis media. At acute otitis media or otitis media with effusion, the tympanic cavity becomes inflamed, accompanied by inflammation of the eustachian tube mucosa and a stenotic tendency. Healing from otitis media is accompanied by decreased eustachian tube mucosa inflammation. We surmise that, depending on how inflammation disappears, fibrosis of the eustachian tube mucosa occurs, leading to a pathologically patulous eustachian tube. Many aspects of the causation of this condition remain unclear, but we surmised that in patients with earlier otitis media, a pathological patulous eustachian tube develops during resolution of inflammation. Our findings indicate the involvement of otitis media as a causative factors in a patulous eustacian tube.     

Panel discussion: Pathogenesis of otitis media. Bacteriology and immunology

Three features of otitis media with effusion (OME) are important in understanding its pathogenesis: 1. it is most common among children, when the eustachian tube is poorly developed; 2. it is most common during the winter months, when the common cold is prevalent; and 3. bacteria are found in a large number of middle ear effusions from OME patients. Although middle ear effusions are conventionally thought to be sterile, numerous recent investigations favor a bacterial pathogenesis of OME. Four possibilities can be considered: 1. bacteria are modified by antibiotics or antibodies, causing a lingering inflammation; 2. early antibiotic treatment may interfere with the development of local immunity; 3. bacterial antigen trapped in the middle ear causes immune injury leading to OME; and 4. bacterial endotoxin and inflammatory mediators cause middle ear effusions.     

Otitis media with effusion: Specific antibody activities against exotoxins in middle ear effusions

Findings of recent immunologic studies on otitis media with effusion indicate that antibodies in middle ear effusions can either originate from serum and/or from local production in the middle ear cavity and Eustachian tube. Determination of specific antibody activity of different immunoglobulin classes in effusions and sera against certain bacterial antigens may aid in a better understanding of the pathogenesis of otitis media with effusion. A radioimmunosorbent assay was employed in the present study to determine specific antibody activity against streptolysin or staphylolysin. Although these antibody activities were mainly limited to IgG and IgA class antibodies in effusion as well as in serum, it was also found that SIgA of various types of the effusion possesses the antibody activity against these exotoxins. Findings of this study suggest that a local immunity functions in the middle ear cavity of patients with otitis media with effusions and that bacterial infection may contribute to the development of middle ear effusion in certain cases.     

Type I allergic reactions of the middle ear and eustachian tube: an experimental study

To clarify the role of type I allergic reactions in etiology and pathogenesis of otitis media with effusion and to determine whether or not the middle ear is an allergic "shock" organ, we made animal models of nasal allergy in guinea pigs by passive sensitization with serum of homologous animals containing specific IgE antibodies. We also examined the eustachian tube, tympanic cavity (histologically), and tubal function after the induction of type I allergic reactions of the nose. However, the involvement of histologic changes was limited only up to the area near the pharyngeal orifice. The tubal dysfunction evoked by nasal allergic reactions was transient, culminating in no middle ear effusion. Upon direct antigen-challenge into the tympanic cavity, allergic changes were observed in the mucosa lining the tympanic bulla, even though no microscopic effusion was present. Findings of the present study suggest that type I allergic reactions of the nose are not an etiologic factor for otitis media with effusion, although the middle ear is potentially an allergic shock organ.     

分泌性中耳炎患者鼻咽癌表面活性物质的检测

通过定量测定健康人及分泌性中耳炎患者鼻咽部灌洗液中代表面活性物质的卵磷脂含量,进一步证实鼻咽部表面活性物质的存在,在探讨ＳＯＤ的发病机理。方法采集健康人和ＳＯＭ患者鼻咽部灌洗液,用分光光度法测定卵磷脂含量并进行对照。