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Myringosclerosis caused by increased oxygen concentration in traumatized tympanic membranes. Experimental study.

The purpose of this study was to elucidate possible relationships between the oxygen concentration of the middle ear cavity and the development of myringosclerosis. Three groups of rats with myringotomized tympanic membranes were exposed to different oxygen concentrations of 10%, 15%, and 40%, respectively, for 1 week. A fourth group was kept in ambient air. Two other groups of rats with myringotomized and intubated tympanic membranes were exposed to oxygen concentrations of 10% and 40%, respectively, for the same period of time. Otomicroscopically, all hyperoxic animals had more numerous myringosclerotic lesions compared with the ambient air group, and also displayed a pronounced hyperplasia of the keratinizing epithelium around the perforation border. By contrast, the hypoxic animals showed less pronounced myringosclerotic lesions or even completely lacked them. It is inferred that an increased oxygen concentration in the middle ear cavity will increase the likelihood of myringosclerotic deposits. The mechanism involved could be related to the formation of oxygen radicals.

Animals↗

Myringotomy: a prerequisite for the development of myringosclerosis?

Streptococcus pneumoniae was inoculated into the left middle-ear cavity in two groups of rats, resulting in purulent otitis media. After 3 days, one group of infected animals and a third group of noninfected animals were subjected to left-sided myringotomy. The tympanic membranes were examined both otomicroscopically and histologically 1 and 3 months later. On otomicroscopic examination the noninfected myringotomized animals had developed extensive myringosclerotic lesions, whereas only minimal sclerotic deposits were noted in the myringotomized animals with acute otitis media (AOM). On histologic examination both the noninfected myringotomized animals and the myringotomized animals with AOM were similar in the frequency and extension of sclerotic lesions in the tympanic membrane. The nonmyringotomized rats with AOM were free of sclerotic lesions, except for minor changes found in one animal.

Acute Disease↗

Sex distribution in children with tympanosclerosis after insertion of a tympanostomy tube.

Tympanostomy tube insertion is an accepted treatment for otitis media with effusion in children. Several clinical studies have shown that tube insertion may cause myringosclerosis. During the period 1988 to 1997 we treated 533 ears from 311 children who had otitis media with effusion by inserting tympanostomy tubes. Most of these (431 ears from 251 children) were re-examined in 1998 and sex and occurrence of myringosclerosis at the tube insertion site were noted. Myringosclerosis was observed in 31% of ears of girls treated with tubes, whereas in boys 71% of ears showed myringosclerosis. This difference between sexes may indicate a genetic predisposition such as that seen in atherosclerosis.

Adult↗

Tympanic membrane/middle ear pathologic correlates in chronic otitis media.

OBJECTIVE: To correlate pathologic findings of the tympanic membrane with pathologic changes in the middle ear cleft in chronic otitis media. STUDY DESIGN: Retrospective. MATERIAL AND METHODS: One hundred-fifty temporal bones from 97 subjects with chronic otitis media (defined as middle ear pathologic changes including granulation tissue, fluid, cholesteatoma, cholesterol granuloma, tympanosclerosis, and ossicular changes) were selected to correlate the presence of these middle ear pathologies with histopathologic changes of the tympanic membrane. The tympanic membrane pathologies included perforation, myringosclerosis, retraction, hemorrhage, fluid-filled cystic spaces, or dilated vessels. Temporal bones were also assessed for atelectasis. Fifty-six normal temporal bones were taken as controls for measurements. RESULTS: Significant correlations between tympanic membrane and middle ear pathology included myringosclerosis and granulation tissue, myringosclerosis and ossicular pathology, retraction and cholesterol granuloma, retraction and cholesteatoma, retraction and ossicular pathology, perforation and ossicular pathology, and hemorrhage and granulation tissue. Additive effects of some pathologies were also observed. Almost half the bones with middle ear pathology had no associated tympanic membrane pathology, whereas multiple pathologic changes in the tympanic membrane generally showed underlying multiple pathologic changes in the middle ear. CONCLUSION: When tympanic membrane pathology is detected otoscopically, its presence, alone or in combination, can be a strong indicator of underlying middle ear pathology. However, a normal-appearing tympanic membrane does not exclude the possibility of middle ear pathology. These findings suggest the need for other diagnostic tools such as multifrequency tympanometry and otoacoustic emissions to complement otoscopy for diagnosis of middle ear pathology, especially in a tympanic membrane that appears "normal."

Adolescent↗

Genetic predisposition for tympanosclerotic degeneration.

Atherosclerosis and tympanosclerosis are disorders that affect different organs in the body. When tissue samples taken from atherosclerotic and tympanosclerotic lesions are compared under light and electron microscopes, common pathological characteristics become apparent in both tissues. These similarities indicate that genetic predisposition to atherosclerosis is also seen in the middle ear. For the purpose of evaluating this genetic predisposition, the incidence of tympanosclerosis in atherosclerotic patients was examined and compared with the normal population. Otoscopic examination of 1,024 atherosclerotic patients was performed, and myringosclerosis was revealed in 66.6%. Myringosclerosis was found in 36 out of 300 non-atherosclerotic patients (12%). In the group of atherosclerotic patients, 174 individuals had past histories of previous ear infections. Myringosclerosis was detected in 147 of these patients (84.5%) during ear examinations. In 637 non-atherosclerotic patients with histories of ear infections, this figure was 114 (17.7%). The high rate of tympanosclerosis observed in atherosclerotic patients in comparison to the normal population was found to be statistically significant. These findings indicate that there must be a genetic predisposition for sclerotic degeneration in some individuals.

Adult↗

Calcium deposition and expression of bone modelling markers in the tympanic membrane following acute otitis media.

BACKGROUND AND OBJECTIVES: In accordance with clinical findings, myringosclerosis develops after otitis media (OM) and paracentesis in an experimental setting. The pathogenesis of this phenomenon of calcification is poorly understood. As the calcification process and the sclerotic plaques of the drum mimics features of bone tissue, this study explores tympanic membrane calcium deposition in association with the expression of three bone modelling markers: osteopontin (OPN), osteoprotegerin (OPG) and osteonectin (ON). OPN is secreted by osteoblasts and is found at calcification sites, e.g. during pathological calcification in chronic OM. The cytokine OPG is an inhibitor of bone resorption and consequently bone remodelling. ON is a calcium binding glycoprotein necessary for the maintenance of bone mass and remodelling. It is found in bone matrix and synthesized by osteoblasts. METHOD: A rat model of acute otitis media (AOM) caused by non-typeable Haemophilus influenzae was used. Four days following middle ear inoculation, a myringotomy was performed in six animals. Another group of ten animals was inoculated only. The drum was dissected in two animals from each group on day 4, 7, 14 and 28 post-inoculation, and the expression of OPN, OPG and ON was determined by immunohistochemistry. von Kossa staining determined the deposition of calcium and immune staining for CD68 identified macrophages. RESULTS: Calcium depositions were initially accumulated in the cytoplasm of macrophages and dispersed in the connective tissue layers of the pars flaccida and tensa. Late accumulation occurred in the lamina propria of pars tensa, more extensively in myringotomized ears. OPN expression was found early in inflammatory cells including especially macrophages and late in pars tensa fibrocytes. OPG expression was initially located to inflammatory cells and late to pars tensa fibrocytes and the inner basal membrane of pars flaccida. Some ears displayed a marked pars flaccida expression of ON in the connective tissue matrix on early days and at the inner basal membrane on later days. The latter cases were from myringotomized ears. Otherwise, no apparent differences of marker expression occurred between myringotomized and non-myringotomized animals. CONCLUSION: We conclude that osteopontin, osteoprotegerin and osteonectin are expressed by different cell types in the tympanic membrane during calcification in association with AOM, with or without myringotomy. These molecules may accordingly play a role in the pathogenesis of myringosclerosis, in which macrophages and fibrocytes appear as potential major players.

Acute Disease↗

Elevated autoantibodies in sera from otosclerotic patients are related to the disease duration.

In this study an indirect ELISA with patients' sera was performed using human collagen type II, double- (dsDNA) and single-stranded DNA (ssDNA), thyroid microsomal antigen, insulin and lysozyme as antigens. Since many preoperated otosclerotic patients demonstrated the signs of myringosclerosis (n=7). they were classified separately and compared with otosclerotic patients without myringosclerosis (n=28), with healthy controls (n=42) and with patients with tympanosclerosis (n=5) of other origin. The otosclerotic patients had serum antibodies to antigens tested similar to normal controls. However, elevated antibody levels to human collagen type II, dsDNA and ssDNA were observed only in patients with a disease duration between 3 and 5 years as compared to other otosclerotic patients. The same duration association was observed in the level of the total serum alkaline phosphatase activity. These observations would suggest that the enzymatic bone resorption is the driving force in human otosclerosis. Elevated serum autoantibodies during tissue reparation in the otosclerotic stage may be a transient response to sustained excess antigen turnover in the primary lesion.

Adolescent↗

Determination of reactive oxygen species in myringotomized tympanic membranes: effect of vitamin e treatment.

OBJECTIVES/HYPOTHESIS: Recent studies have established a strong relationship between the development of myringosclerosis and reactive oxygen species (ROS). The aims of the present study were to directly detect ROS in the tympanic membrane and middle ear mucosa of rats by measuring luminol amplified chemiluminescence, to evaluate the changes in the levels of ROS after treatment with vitamin E, and to examine the possible changes in the tympanic membranes otomicroscopically and histologically. STUDY DESIGN: Prospective controlled animal study. METHODS: Forty healthy Sprague-Dawley rats were divided into five groups of eight animals each. Animals in all groups except group 1 were bilaterally myringotomized. Group 2 received no treatment, group 3 was treated with topical olive oil, group 4 received topical vitamin E, and group 5 received intramuscular vitamin E. After 24 hours of myringotomy, tympanic membranes were examined otomicroscopically; thereafter, tympanic membranes and middle ear mucosa were peeled off. The right ears of the animals were used for biochemical assay, and the left ears were used for histological study. RESULTS: Reactive oxygen species levels were significantly decreased in group 4 with topical application of vitamin E compared with untreated and myringotomized animals in group 2. Reactive oxygen species levels were also decreased in group 5, although the decrease was not statistically significant when compared with groups 2 and 3. Histological studies confirmed sclerotic changes in the untreated myringotomized animals. The tympanic membranes of animals in groups 2 and 3 showed a white, chalk-like pattern of sclerotic changes, whereas animals in groups 4 and 5, with the exception of two animals in group 5, lacked these changes. CONCLUSION: Although the relationship between the development of myringosclerosis and ROS had been well documented previously, the present study is the first that has directly measured the levels of ROS in the tympanic membrane and middle ear mucosa. These results are relevant because they correlate with histological findings. It has also been demonstrated that topically applied vitamin E is effective in decreasing the ROS levels.

Administration, Topical↗

Does passive smoking affect the outcome of grommet insertion in children?

Bilateral myringotomy with insertion of ventilation tube (grommet) is the most common surgical procedure done on children under general anaesthetic. A prospective study was conducted on children undergoing grommet insertion to ascertain any relationship between exposures of passive smoking to the outcome of grommet insertion. Six hundred and six children (with 1174 ears) who underwent grommet insertion for recurrent secretory otitis media were followed up till the grommets were extruded. Thirty-three children (65 per cent), whose mothers smoked when they were pregnant, had bilateral narrow external ear canals. The median survival rate of grommet was 59 weeks in children who were exposed to passive smoking as compared to 86 weeks for non-exposed children and the extrusion rate of grommet was 36 per cent higher at the end of one year if both parents smoked compared to the non-smoking group. Post-extrusion myringosclerosis was 64 per cent if both parents smoked and less than 20 per cent if neither parents smoked. It is concluded that post-operative infection rate, attic retraction, post-extrusion myringosclerosis and permanent perforations of tympanic membrane were more common in children exposed to passive smoking. The study provides further support to professional and governmental advice that passive smoking is harmful.

Adolescent↗

Sequelae of secretory otitis media: changes in middle ear biomechanics.

A new method previously introduced investigating the pressure volume relationship of the middle ear system describes dynamic mechanical properties of the system: the variables measured are hysteresis, compliance, and P(ec0) expressing the zero position of the tympanic membrane. The present study investigates the mechanical properties in 69 adolescents treated with ventilation tubes during childhood due to secretory otitis media. The tympanic membranes displayed various degrees of atrophy, sclerosis, and retraction of the pars flaccida. Atrophy was quantitatively related to decreasing hysteresis and increasing compliance, while myringosclerosis showed opposite effects. P(ec0) was significantly lower for the group of former secretory otitis media than for normals (p < 0.001). This reflects a retraction pattern of the tympanic membrane, which may be explained by a low opening pressure of the eustachian tube or previous pressure load of the drum. Signs of retraction were not found by tympanometry. Treatment with ventilation tubes was associated with a dramatic increase of tympanic membrane pathology (66%) compared to untreated ears (12%), as assessed by otomicroscopy (p < 0.001). However, these changes specific to treatment were not found in the corresponding mechanical variables of the middle ear system, as the effects of combined atrophy and myringosclerosis tend to counterbalance.

Acoustic Impedance Tests↗

Development of tympanosclerosis: can predicting factors be identified?

HYPOTHESIS: The etiological hypothesis is that there might be factors triggering an immunological chain reaction that eventually leads to tympanosclerosis formation. BACKGROUND: Tympanosclerosis is a condition leading to a calcification process in the middle ear and, occasionally, also to the lining of the inner ear. This sometimes leads to hearing loss due to fixation of the middle ear ossicles. In severe cases. deafness may occur as a result of the inner ear impairment. Surgery is the treatment offered, often with poor long-term results, and, alternatively, prescription of hearing aids. Some patients develop tympanosclerosis after mild inflammatory otitis media processes whereas some heal without tympanosclerosis after more aggressive infections. This difference may be due to individual variations in the inflammatory response. The biological mechanism of calcification in tympanosclerosis is probably similar to that occurring in other calcifying tissues due to diseases. METHODS: The present investigation was performed to develop methods for immunohistochemical analyses of this delicate tissue consisting of both hard bone and the very thin tympanic membrane. Sprague-Dawley rats were inoculated with a suspension of Streptococcus pneumoniae, type 3, into the middle ear and sacrificed after 1 week up to 6 months. A new technique was elaborated where the whole specimen was prefixed briefly and then en bloc incubated with the primary antibodies and after that decalcified in edetic acid (EDTA). Primary antibodies against macrophages were used for the immunohistochemical staining. RESULTS: Acute otitis media was successfully induced in the rats and myringosclerosis was seen in 30% of the animals, often localized close to the bony frame where macrophages could also be detected. CONCLUSIONS: Acute otitis media and myringosclerosis were introduced in the animals. Conventional immunological techniques were tested on this delicate tissue. A new method for immunohistochemical staining was elaborated in which specimens were stained en bloc before decalcification and sectioning were performed. Expression of macrophages was demonstrated in the tympanic membrane.

Animals↗

Chronic otitis media with effusion sequelae in children treated with tubes.

OBJECTIVE: To determine incidence and prevalence of middle ear sequelae and abnormal tympanometry results among children with chronic otitis media with effusion (OME) who received standard treatment with tympanostomy tubes. DESIGN: Prospective cohort study. SETTING: Community clinic and academic medical center. Patients A total of 140 children followed up for 8 years after tube treatment. MAIN OUTCOME MEASURES: Tympanic membrane perforation, atrophy, retraction, hearing loss, myringosclerosis, low static admittance (SA) and broad-peaked tympanogram, high SA and narrow-peaked tympanogram, and negative tympanometric peak pressure. RESULTS: Annual incidence of sequelae was typically greater during 3 to 5 years than 6 to 8 years of follow-up. Greatest increases in incidence during the 5-year follow-up were for atrophy (67%), high SA and narrow-peaked tympanogram (70%), and retraction pocket (47%). Prevalence of these sequelae also increased over time, whereas low SA and broad-peaked tympanogram and negative tympanometric peak pressure decreased during follow-up. Sequela tended to become bilateral over time, and concordance of different sequelae in the same ear was low (kappa, 0.05-0.42). CONCLUSIONS: Annual incidence of sequelae decreased during follow-up. This finding parallels decreasing incidence of OME and tube placement as children mature and demonstrates that sequelae are more likely to develop during active acute and chronic OME. The cumulative effect of incidence resulted in few ears free of sequelae by 8 years of follow-up. Based on this cohort of healthy children with OME, although the risk of sequelae decreased over time, functional and morphologic sequelae were prevalent and may put children at risk for continuing middle ear problems as they grow into adolescence and adulthood.

Acoustic Impedance Tests↗

Grommets in otitis media with effusion: the most frequent operation in children. But is it associated with significant complications?

INTRODUCTION: Otitis media with effusion is one of the most frequent diseases in children, and its management requires the attention of general practitioners, pediatricians and ear, nose and throat (ENT) surgeons. The main complications associated with tympanostomy tube insertion, are: (1) purulent otorrhea (10-26% of cases), in which local otic preparations might be effective, and biofilm-resistant tubes may decrease this complication in the future; (2) myringosclerosis (39-65% of operated ears), with usually no serious sequelae; (3) segmental atrophy (16-75% of cases); (4) atrophic scars and pars flaccida retraction pockets (28 and 21% of operated ears, respectively); (5) tympanic membrane perforations (3% of cases, although with T-tubes, the incidence may be as high as 24%); (6) cholesteatoma (1% of cases), although tympanostomy tubes may sometimes prevent, rather than contribute to its development; (7) granulation tissue (5-40% of instances), when the duration of tube retention is prolonged. CONCLUSION: It would appear that the complications associated with tympanostomy tube insertion are more frequent than anticipated, reaching 80% of operated ears under specific circumstances and in certain subgroups of children. These complications may resolve with conservative management, but in persistent cases surgical removal of the tubes is mandatory.

Child↗

Eustachian tube function and tympanic membrane findings after chronic secretory otitis media.

OBJECTIVE: The etiology of secretory otitis media (SOM) is multifactorial. The main factors discussed are infection and tubal dysfunction. This study aimed to detect poor tubal function and tympanic membrane pathology in young adults after extremely long-standing SOM. METHODS: Thirty-four patients, 16-25 years old, with previous chronic SOM persisting at least 6 years (mean 11.2 years, range 6.2-18.6 years), were retrospectively examined at a mean of 18 years after their first myringotomy or tube insertion and comparison was made with 15 controls. The medical records were scrutinized, otomicroscopic examination was performed and the Eustachian tube function was studied in a mini pressure chamber. RESULTS: The mean age at SOM onset was 2.4 years (range 0.5-8.4 years) and the mean period from the last myringotomy or when the last tube had disappeared to follow-up was 6.7 years (range 1.3-12.8 years). Tympanic membrane pathology was found in 76% of the ears of SOM patients and in none (0%) of controls (P<0.001). The youngest patients had more atrophy than the older patients (P<0.05) and more myringosclerosis was observed in patients with shorter interval between SOM ending and examination. The patients were found to have significantly poorer active tubal function; i.e. higher inability to equilibrate negative or negative and positive middle ear pressure, compared with controls (P<0.001). The majority of the patients (74%) still experienced some kind of discomfort in their ears at the time of examination. CONCLUSIONS: Still in adulthood patients with chronic SOM during childhood exhibit dysfunction of the tube and tympanic membrane pathology to a high extent.

Adolescent↗

[The effectiveness of otoendoscopy in myringoplasty using adipose graft].

OBJECTIVE: The aim of this study was to present our results of endoscopic-guided myringoplasty using adipose graft tissue. Due to its simplicity and reliability, this technique seems be as efficient as other classical graft techniques (fascia temporalis, perichondrium...). PATIENTS AND METHODS: We analyzed data from 81 patients operated on for a tympanic perforation between 1993 and 2002 using an endoscopic-guided technique with adipose graft. Patients were evaluated postoperatively at seven days, one month and three months. Criteria of success were complete closure of the tympanic membrane, absence of lateralization of the tympanic membrane and no audiometric impairment. RESULTS: Treatment was successful in 920f patients with at least two years follow-up. The failures occurred in patients with contraindications such as myringosclerosis, myringitis and perforation size greater than 500f the tympanic surface. CONCLUSION: Endoscopic-guided myringoplasty using an adipose tissue graft is a rapid, safe, reliable and efficient procedure that should be performed in first intention for selected indications.

Adipose Tissue↗

Possible inflammatory mediators in tympanosclerosis development.

OBJECTIVE: Tympano/myringosclerosis is a sequelae following otitis media, causing hearing disability. There is no curative treatment for this condition. In order to illuminate the correlation of inflammatory mediators in otitis media and tympanosclerosis development, the present study was performed. METHODS: In an animal model, Streptococcus pneumonia bacteria were inoculated to the middle ear. Furthermore, biopsies were harvested during surgery, from children suffering from secretory otitis media and from patients with already established tympanosclerosis. The early inflammatory parameters were investigated in the rat model as well as in the patient material. The lymphocytic population, macrophages, interleukin-6, inducible nitric oxide synthase and MHC class II were studied by immunohistochemistry and by mRNA in situ hybridization. RESULTS: Myringosclerosis was produced in 30% of the rats studied. Macrophages were the first cells to invade the middle ear after induction of otitis media, followed by B-cells and T-cells. IL-6 m-RNA was found as early as 1 h after inoculation. Cells, expressing inducible nitric oxide synthase, seemed to be activated macrophages. Osteoclast like cells, positive in immunohistechemical macrophage staining, were found close to the insertion of the tympanic membrane. The human specimens showed a more immunological active stage in the secretory otitis media group as compared to the specimens with tympanosclerosis. CONCLUSIONS: The immunocompetent cells and some mediators are presented time dependently in otitis media and a possible reaction sequence, leading to differentiation of macrophages into osteoclasts is presented. This may lead to tympanosclerosis development.

Animals↗

Otological problems in children with Turner's syndrome.

Ear and hearing disorders are common problems among girls and women with Turner's syndrome. During infancy and childhood the girls often suffer from repeated attacks of acute otitis media and later in life the women frequently complain of a rapid onset of social hearing problems due to sensorineural hearing impairment. A study of 56 girls aged 4-15 years with Turner's syndrome was performed to investigate the prevalence of eardrum pathology and hearing impairment in young children and teenagers with Turner's syndrome. A possible relation to karyotype was also investigated. A high prevalence (61%) of recurrent acute otitis media was found in the study group and 32% had been treated with ventilation tubes. Fifty-seven percent showed eardrum pathology, such as effusion, myringosclerosis, atrophic scars, retraction pockets and perforations. Auricular anomalies were noted in 23% of the cases, most commonly in the 45, X group. The audiometric analysis showed conductive hearing loss (air-bone gap > 10 dB HL) in 43% and the typical sensorineural dip in the middle frequencies was found in 58% of the girls, of whom the youngest was 6 years old. Four percent were using hearing aids. The data of this study further confirm that the dip is progressive over time and may be detectable as early as at the age of 6, giving a chance to predict a future hearing loss. The findings emphasize the importance of regular otological examinations and audiological evaluations of all girls with Turner's syndrome early in life.

Acute Disease↗