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ABSTRACT: Ecalectin, which is produced in the mucosa of nasal polyps, seems to play an important role in the accumulation and activation of eosinophils in nasal polyps, regardless of the presence or absence of atopic predisposition.
Ecalectin is a recently discovered eosinophil chemoattractant which elongs to the galectin family. We investigated the expression of ecalectin in nasal polyp tissues associated with various nasal and paranasal diseases in order to clarify the pathogenesis of eosinophilia in nasal polyposis.
Nasal polyps were taken from 56 patients diagnosed as having chronic sinusitis with nasal polyposis. The surgically resected polyps and nasal turbinates were immunohistochemically stained using antibodies against EG2, human mast cell tryptase, CD3 and ecalectin.
The number of EG2- and ecalectin-positive cells was significantly higher in nasal polyps than control turbinates. Ecalectin-positive cells were observed in the subepithelial layer, where many EG2-positive cells were present. The number of ecalectin-positive cells correlated significantly with the number of EG2-positive cells in nasal polyps. Many ecalectin mRNA-positive cells were also observed in nasal polyps with an accumulation of EG2-positive cells.
Acta Oto-Laryngologica 02/2006; 126(1):43-50. · 1.08 Impact Factor
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ABSTRACT: Patients with intractable otitis media associated with bronchial asthma have an extensive accumulation of eosinophils in the effusion and mucosa of the middle ear; this condition is called eosinophilic otitis media (EOM). It remained to be determined how eosinophils accumulate in the middle ear.
To clarify the pathogenesis of middle ear diseases, we measured the concentration of eosinophil chemoattractants in middle ear effusion (MEE), and carried out immunohistochemical studies of middle ear mucosa specimens to demonstrate the expression of eosinophil chemoattractants.
Middle ear effusion samples were obtained from 15 EOM patients with bronchial asthma and from six controls for the measurement of eosinophil cationic protein (ECP), IL-5, eotaxin and regulated on activation, normal T expressed and secreted concentrations. Middle ear mucosa samples were also taken from 14 EOM patients and 16 controls for immunohistochemical study. In 10 EOM patients, the numbers of immunoreactive cells as well as apoptotic cells were determined before and after the topical application of triamcinolone acetonide into the middle ear.
In EOM, significantly higher ECP and IL-5 concentrations were detected in MEE than in serum, and ECP, IL-5 and eotaxin concentrations in MEE were higher in the EOM patients than in the controls. ECP concentration positively correlated with that of IL-5. Immunohistochemically, the numbers of cells positive for EG2 and ecalectin were significantly higher in the EOM patients than in the controls. After the topical application of triamcinolone acetonide, the numbers of infiltrating cells and immunoreactive cells distinctly decreased, whereas the number of apoptotic cells significantly increased.
In EOM, locally produced IL-5 may play a crucial role in the accumulation of eosinophils in the middle ear. Chemokines such as ecalectin and eotaxin are also produced in the middle ear, and help activate and enhance the survival of eosinophils to induce the intractable condition in the middle ear. The topical application of triamcinolone acetonide induces the apoptosis of not only eosinophils but also eosinophil chemoattractant-producing cells, thereby improving the middle ear condition.
Clinical & Experimental Allergy 11/2005; 35(10):1370-6. · 5.03 Impact Factor
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ABSTRACT: Many reports about the effect of aging on hearing results after tympanoplasty have been published. However, they have not been evaluated comprehensively, i.e. by taking into consideration other aspects which also affect the outcome. In this study, the effect of aging on hearing results after canal wall reconstruction tympanoplasty was assessed in 236 consecutive ears of 213 patients > 20 years old with middle ear cholesteatoma. The elderly group (n = 34), defined as patients > or = 60 years old, was compared to the younger groups in terms of hearing results of postoperative hearing level, hearing gain, A-B gap and change in bone conduction hearing level at 4000 Hz after adjustment for age, gender, staged operation, preoperative hearing level and type of tympanoplasty, all of which affect hearing results, using the generalized linear regression method. Postoperative hearing level and hearing gain were found to be better amongst patients aged 20-29 and 30-39 years than in the elderly group, whilst A-B gap did not differ between all age categories. Within the elderly group, air conduction hearing level was shown to have improved after surgery. Changes in bone conduction hearing level at 4000 Hz were not significantly different between the age groups, suggesting that operative stress, i.e. mechanical stress or ossicular manipulation stress, does not aggravate sensorineural hearing loss in the elderly. We conclude that surgeons should be encouraged to perform tympanoplasty aimed not only at eradicating the lesion itself but also at improving hearing acuity in the elderly.
Acta Oto-Laryngologica 01/2002; 121(8):919-24. · 1.08 Impact Factor
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ABSTRACT: Materials were 236 ears of 213 patients with middle ear cholesteatoma undergoing canal wall reconstruction during 1993-1998. Subjects were followed up for at least 1 year after final operation. Of 236 ears, 147 (62%) underwent 1-stage operation and 89 ears (38%) required 2-stage operation. Hearing results were successful in 157 ears (67%) based on criteria proposed by the Otological Society of Japan. The success in ears undergoing 1-stage operation was 74% and 54% in ears undergoing 2-stage operation. Postoperative hearing and air-bone gap in the 1-stage group were significantly better than in the 2-stage group. For tympanoplasty, success was 97% in type I, 64% in type III, and 53% in type IV. The likelihood of undergoing 2-stage operation increased with the type of tympanoplasty, from type I to IV. Postoperative hearing was significantly worse in older age groups. Of the 89 ears, 13 (15%) had recurrent cholesteatoma and 29 (33%) had residual cholesteatoma at 2-stage operation. In the 135 in the 1-stage group, recurrent cholesteatoma was observed at follow-up in 13 ears (9.6%). When we analyzed clinical risk factors for both recurrent and residual cholesteatoma in age, gender, otorrhea, types of cholesteatoma, and types of tympanoplasty, no significant factors were seen for recurrent or residual cholesteatoma. These results indicate that canal wall reconstruction tympanoplasty for middle ear cholesteatoma yields relatively good hearing results. However, more effort is needed to reduce the incidence of recurrent and residual cholesteatoma.
Nippon Jibiinkoka Gakkai Kaiho 10/2001; 104(9):843-51.
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ABSTRACT: Although patients with intractable otitis media associated with bronchial asthma have extensive accumulation of eosinophils in the middle ear mucosa and middle ear effusion, systematic histological and immunohistochemical studies have not been performed.
To clarify the pathogenesis of middle ear diseases, we carried out immunohistochemical studies on middle ear specimens, particularly focusing on the characteristics of accumulated eosinophils.
Middle ear specimens obtained from eight adult patients and from 17 controls were immunohistochemically stained using monoclonal antibodies against EG1, EG2, mast cell tryptase, IgA and IgE. The concentration of eosinophil cationic protein (ECP) in middle ear effusion samples was also measured.
In the asthmatic patients, severe round-cell infiltration was observed in the submucosa and most of the EG1-positive cells were also EG2-positive. In the control patients, the mucosa showed a fibrotic change with a few inflammatory cells, and EG1- or EG2-positive cells were quite few. The expression of IgE was found not only on the surface of mast cells but also within the plasma cells in the asthmatic patients, and the number of IgE-positive cells was about twice as high as that of mast cells. A significantly higher concentration of ECP was noted in middle ear effusion obtained from the asthmatic patients than that from the control patients.
Most of the eosinophils in the middle ear mucosa and middle ear effusion were activated, resulting in degranulation and release of ECP, and local IgE production occurs in the middle ear mucosa, indicating that the intractable inflammation is closely associated with IgE-mediated late phase response with eosinophil accumulation.
Clinical & Experimental Allergy 08/2001; 31(7):1135-43. · 5.03 Impact Factor
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ABSTRACT: To investigate post-operative hearing results in children with middle ear cholesteatoma, and to analyze the correlation between hearing results and clinical factors and findings before and during the operation.
One hundred and twenty-four ears of 123 children were operated on for middle ear cholesteatoma at the age of 10 years or younger by canal wall reconstruction tympanoplasty and were followed up more than 1 year after the final operation. We evaluated the average air and bone conduction hearing levels at the speech ranges before the first operation (pre-operative hearing) and after the final operation (post-operative hearing).
The mean of the average air conduction hearing level of 124 ears was significantly improved from 34.7 to 27.1 dB after the final operation. Among them, 84 ears (67.8%) showed a hearing level of 30 dB or less post-operatively. Post-operative hearing was better in the one-stage group than in the staged group. However, more than one-half of the ears which underwent type IV tympanoplasty in the staged group showed post-operative air conduction hearing level of < or =30 dB. Significant improvement in post-operative hearing was noted in ears with normal middle ear mucosa or middle ear effusion at the final operation. No correlation between hearing improvement and clinical factors such as age, type of cholesteatoma or presence of otitis media with effusion at the first operation was found.
Children with middle ear cholesteatoma at the age of 10 years or younger exhibited good hearing post-operatively. Satisfactory hearing improvement is expected even in ears without the superstructure of the stapes if staged tympanoplasty is conducted. Canal wall reconstruction tympanoplasty for pediatric cholesteatoma was successful in terms of hearing results and the success was unrelated to various clinical factors.
International Journal of Pediatric Otorhinolaryngology 07/2001; 60(1):65-72. · 1.17 Impact Factor
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ABSTRACT: To clarify the basis of macrolide therapy for improvement of chronic sinusitis, we investigated the effect of macrolides on the expression of HLA-DR and costimulatory molecules such as CD54 and CD80 on macrophages in nasal polyps. Nasal polyps taken from 54 patients who had or had not been treated with macrolides were immunohistochemically studied. The percentages of CD68-positive macrophages expressing HLA-DR or CD54 were not significantly different between patients treated with macrolides and those not treated with macrolides. However, among patients exhibiting no atopic predisposition, the number of CD80-positive macrophages was higher in patients treated with macrolides than in those not treated. In addition, the percentage of CD80-positive macrophages was negatively correlated with the percentage of infiltrating eosinophils in the polyps. These results demonstrate that macrophages act as antigen-presenting cells, expressing both major histocompatibility complex II and costimulators, and that the expression of CD80 may play a key role in the immune responses occurring in a nasal polyp. Macrolides may modulate the mucosal immune responses through CD80 expression.
The Annals of otology, rhinology, and laryngology 06/2001; 110(5 Pt 1):457-63. · 1.05 Impact Factor
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ABSTRACT: A 49-year-old male developed left abducens nerve palsy as a result of metastatic spread of carcinoma of the cervical esophagus to Rouviere's node and infiltration of the petrous portion of the left temporal bone. Postmortem temporal bone histology revealed that cancer cells had invaded the greater superficial petrosal nerve (GPN), lesser superficial petrosal nerve, tensor tympani muscle (TTM) and the skin covering the anterior wall of the left external auditory meatus. These findings suggest that the carcinoma metastasized from the cervical esophagus to Rouviere's node and directly invaded the middle cranial fossa and then the temporal bone, and further infiltrated the middle ear via perineural invasion.
Auris Nasus Larynx 05/2001; 28(2):169-72. · 0.76 Impact Factor
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The Japanese journal of antibiotics 03/2001; 54 Suppl A:10-11.
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ABSTRACT: The most common symptoms of patients with carcinomas of the middle ear or mastoid are otorrhea, facial paralysis, and hearing loss, including a sensorineural element and vertigo. The latter two symptoms are indicators of inner ear damage. However, few reports have been made concerning the histopathological changes that occur in the inner ear in the presence of a tumor. The present study was performed to determine the pattern of tumor invasion in the inner ear and the histopathological changes that occur in the inner ear in cases of ear carcinomas. Temporal bone sections from five patients (age: #39-73 years; 3 males and 2 females) who died from a primary carcinoma of the ear were studied histologically. The following features were examined: 1) localization of the tumor in the temporal bone, 2) pattern of tumor invasion in the inner ear, 3) pathological changes in the inner ear, including the cochlea, vestibule and semicircular canals. Tumor cells were still present in the temporal bone sections of all the patients except one, even though the patients had received various treatments for the carcinoma, including radiation therapy, surgery and chemotherapy. Marked inflammatory and necrotic changes were observed in cases where the tumor had invaded the external auditory canal, middle ear cleft, internal auditory canal, and in some cases the inner ear. In cases where the tumor invaded the inner ear via the internal auditory canal rather than directly from the middle ear, the otic capsule is thought to have acted as a barrier against tumor invasion. In addition, marked degenerative changes throughout the entire inner ear structures were noted. These changes may have arisen from an attenuated blood supply to the inner ear as a result of pressure from the tumor in the internal auditory canal, tumor infiltration of the labyrinthine artery.
Nippon Jibiinkoka Gakkai Kaiho 11/2000; 103(10):1141-9.
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The Japanese journal of antibiotics 02/2000; 53 Suppl A:39-41.
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ABSTRACT: In order to secure both long-lasting carefree ears and hearing-preservation/restoration, the best method to apply is the closed-method tympanoplasty, especially for cholesteatomatous otitis media in children. We agree with this method, in spite of the high percentages of postoperative residual cholesteatoma in children. Until a better way of irradicating cholesteatoma becomes available, either staged operations or periodical check-ups for many years are mandatory. While postoperative attic retraction/cholesteatoma formation seems to be preventable in most cases, the rate of residual cholesteatoma is very high in our data and in other reports. Looking for a reason, the differences between the cholesteatoma in children and those in adults are to be investigated in macro-, micro- and ultramicroscopic observations. In addition, basic rather than clinical studies on cholesteatoma in children are requested.
International Journal of Pediatric Otorhinolaryngology 11/1999; 49 Suppl 1:S91-3. · 1.17 Impact Factor
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ABSTRACT: Although the insertion of tympanostomy tubes is regarded as an effective treatment for otitis media with effusion in the general population, it remains to be determined whether tympanostomy tube insertion is also effective for otitis media with effusion in children with Down syndrome. The present study was carried out to determine the efficacy of tympanostomy tube insertion in children with Down syndrome.
We studied 28 children (18 males and ten females) with Down syndrome and 28 age-matched control children who underwent tympanostomy tube insertion and were followed up for more than 2 years, up to 7 years of age or older. The children were followed up every month for 6 months after the operation and every 2 months thereafter. The tympanostomy tubes were not removed unless granulation tissue appeared around the ventilation tubes.
The cure rate for otitis media with effusion was lower in the children with Down syndrome than in the age-matched control children. Sequelae of otitis media with effusion (atelectatic eardrum, permanent perforation of the eardrum and middle ear cholesteatoma) were significantly often encountered in the former group. The children with Down syndrome had more frequent episodes of otorrhea from the tympanostomy tubes than the control children and antibiotic-resistant-bacteria were frequently isolated. Moreover, improvement in hearing acuity after the placement of tympanostomy tubes was not always achieved in children with Down syndrome.
The efficacy of the tympanostomy tube insertion for children with Down syndrome was much lower than in control children. We propose that in children with Down syndrome conservative management should be the treatment of first choice and that the insertion of tympanostomy tubes should be indicated only when hearing loss due to middle ear effusion is in a severe degree and when pathological changes of the eardrum, such as adhesion and deep retraction pocket formation, are going to occur.
International Journal of Pediatric Otorhinolaryngology 09/1999; 49(2):143-9. · 1.17 Impact Factor
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ABSTRACT: In infancy the head of the malleus and body of the incus normally contain bone marrow, which is gradually replaced by bone and converted into vascular channels with age. This study was carried out to clarify the age at which ossification of the ossicles is complete and to examine factors influencing the ossification process.
Human temporal bone sections from 32 infants and children with or without congenital anomalies, aged 1 day to 9 years, who were born at term were studied.
The percentage bone marrow area occupying the head of the malleus and body of the incus was calculated in three horizontal temporal bone sections for each case, using computer-aided digital processing of images.
Bone marrow was observed in both the malleus and incus in children until 25 months of age, while after the age of 25 months no bone marrow tissue was present in either of the ossicles. It appeared that the bone marrow space disappeared somewhat earlier in the malleus than in the incus. The bone marrow space around the otic capsule disappeared much earlier than that within the ossicles. The age at completion of ossification was correlated with neither the presence of congenital anomalies nor the presence of residual mesenchyme in the middle ear.
Ossification of the ossicles seems to occur steadily throughout fetal life and after birth during development of the middle ear. Although the clinical significance of postnatal residual bone marrow within the ossicles is not known, it possibly plays a role as a blood-forming organ in early infancy.
The Laryngoscope 07/1999; 109(6):927-30. · 1.75 Impact Factor
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ABSTRACT: To clarify the risk factors for the development of recurrent and residual cholesteatoma in children.
We studied 84 ears of 83 children aged 10 years or younger who underwent a second stage operation 1 year after primary surgery with a canal wall reconstruction procedure, and analyzed the clinical risk factors for recurrent and residual cholesteatoma.
Recurrent cholesteatoma was detected in 21 ears (25%) and residual cholesteatoma was noted in 35 (42%) of 84 ears. With respect to recurrent cholesteatoma, significant risk factors were determined to be male gender, pars flaccida type of cholesteatoma and the association of otitis media with effusion either in the side affected by cholesteatoma or on the opposite side. On the other hand, congenital type of cholesteatoma was a significant negative risk factor. With respect to residual cholesteatoma, the only risk factor was a posterosuperior type of cholesteatoma. Residual cholesteatoma was sometimes found even when the surgeon had declared complete removal of the cholesteatoma matrix at the time of primary surgery.
High incidence of recurrent and residual cholesteatoma was noted at the second stage operation. Occurrence of recurrent cholesteatoma is closely related to eustachian tube dysfunction. Thin and highly proliferative cholesteatoma matrix in children may be responsible for high occurrence of residual cholesteatoma. Therefore, planned staged surgery is preferable to single stage surgery for the treatment of pediatric cholesteatoma.
International Journal of Pediatric Otorhinolaryngology 12/1998; 46(1-2):57-65. · 1.17 Impact Factor
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ABSTRACT: The temporal bones of two patients with profound bilateral deafness from infancy were studied immunohistochemically, using a neurofilament protein antibody to detect the cochlear neuronal elements. One patient exhibited Mondini dysplasia of the inner ear, with the organ of Corti almost completely deteriorated. The other patient is the first reported case involving complete aplasia of the organ of Corti in all turns. In both cases, the immunohistochemical staining clearly revealed a severe reduction in the number of afferent neurons, such as dendrites, spiral ganglion cells and cochlear axons. The number of efferent spiral bundles in the osseous spiral lamina and intraganglionic portion also decreased in parallel with the reduction in the number of cochlear afferent neurons. Our results are inconsistent with previously reported cases of presbycusis and acquired deafness induced by the measles virus, in which efferent neurons were preserved while afferent neurons degenerated. The loss of both the efferent and afferent neurons might be characteristics of congenital deafness.
Ear, nose, & throat journal 09/1998; 77(8):662-6, 668. · 0.66 Impact Factor
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ABSTRACT: To clarify mastoid pneumatization in children with congenital cholesteatoma and compare their clinical characteristics.
The mastoid pneumatization of 34 children with congenital middle ear cholesteatoma, of 34 age-matched children with unilateral acquired cholesteatoma, and of 17 age-matched control children without middle ear diseases was studied.
The sizes of the mastoid cells were measured from 1.5-mm sliced semiaxial sections of a temporal bone computed tomography scan. The sum of the two areas from the two images, one showing the lateral semicircular canal and the other, 3 mm below this, was defined as the area of the pneumatized mastoid cells.
The mastoid cells in ears of children with congenital cholesteatoma were poorly pneumatized compared with those of control children without middle ear diseases, but were better pneumatized compared with those of children with acquired cholesteatoma. In children with congenital cholesteatoma, the degree of pneumatization in the cholesteatoma side was significantly poorer than that in the opposite side. A well-pneumatized mastoid was seen in ears with no episode of otitis media, in ears with the open-type cholesteatoma, and in ears with ossicular anomalies.
The presence of cholesteatoma matrix accelerates the inflammatory response when middle ear infections occur, and this probably leads to the suppression of mastoid pneumatization. The authors also propose the hypothesis that cholesteatoma in most congenital cases is the open type, and that middle ear inflammation may contribute to the formation of cystic and closed-type cholesteatoma.
The Laryngoscope 08/1998; 108(7):1071-6. · 1.75 Impact Factor
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ABSTRACT: It is well known that congenital anomalies are often associated with malformation of the inner, middle and external ear. In temporal bone studies, it has been found that abnormality of the facial nerve often occurs in patients with congenital aberrations. The temporal bone collections of the Teikyo University School of Medicine include 32 human temporal bones obtained from 19 infants ranging in age from one day to 7 months, who had chromosomal aberration and severe visceral anomalies. We histologically studied routinely processed sections of these temporal bones under a light microscope. Facial anomaly was observed in 20 of the 32 ears (63%). An abnormal course was observed in 18 ears (56%); 5 ears showed hypoplastic development, 4 showed displacement of geniculate ganglion cells into the internal auditory meatus, and 3 ears showed bifurcation. Abnormal course of the facial nerve was found in a significant number of ears with aural and mandibulal abnormalities (76%). However patients with multiple inner ear anomalies showed an abnormal course and hypoplasia of the facial nerve. There was no correlation between the incidence of facial abnormalities and inner ear anomalies.
Nippon Jibiinkoka Gakkai Kaiho 03/1998; 101(2):192-7.
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The Japanese journal of antibiotics 02/1998; 51 Suppl A:25-6.
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The Japanese journal of antibiotics 02/1998; 51 Suppl A:100-2.
