Hearing loss in facioscapulohumeral muscular dystrophy.

The coincidence of facioscapulohumeral muscular dystrophy (FSHD) with sensorineural hearing loss and retinal abnormalities might imply genetic heterogeneity of FSHD. We performed screening audiometry in 56 patients with autosomal dominant FSHD and in 72 healthy family members, and found that the difference in hearing level between 4,000 Hz and 6,000 Hz was significantly greater in FSHD patients than in controls, independently both for the left and right ear. We conclude that this change of hearing function is part of the disease and may lead to severe hearing loss in some patients. The fact that it was present in all families is another argument against genetic heterogeneity.

Effect of implantation site on phagocyte/polymer interaction and fibrous capsule formation.

Implants of Silastic, Estane, polypropylene oxide and an HPOE/PBT segmented polyether polyester copolymer were qualitatively and quantitatively evaluated, with respect to interaction with mononuclear and multinucleated phagocytes as well as fibrous capsule formation, after implantation at three sites in the rat middle ear. The volume of the phagocyte exudate surrounding the implants, the degree of implant degradation and fragmentation and the thickness of the fibrous capsules were found to be correlated with the implantation site. From these findings, it can be concluded that it is important to assess the biological performance of a biomaterial at carefully chosen implantation sites.

Macropore tissue ingrowth: a quantitative and qualitative study on hydroxyapatite ceramic.

The aim of this study was to obtain more information about macropore tissue ingrowth into the pores of sintered hydroxyapatite implanted in the rat middle ear, for the assessment of the usefulness of this material in reconstructive middle-ear surgery. The exudate filing the pores during the early post-operative period was gradually replaced by equal amounts of fibrous tissue and bone. The percentage of the macropore area occupied by bone was directly correlated with the macropore size. Bone was deposited not only from the pore wall towards the pore centre, but also in the opposite direction. Bonding osteogenesis was demonstrated. At sites of mechanical irritation, the presence of multinucleated cells and proliferatively active mononuclear phagocytes persisted for as long as a year. Under appropriate conditions hydroxyapatite seems to be a promising material for bone substitution in reconstructive middle-ear surgery.

Bioreactions at the tissue/hydroxyapatite interface.

The events at the hydroxyapatite implant material/tissue interface in the rat middle ear were studied by light microscopy, autoradiography, morphometry, transmission electron microscopy (TEM), scanning electron microscopy (SEM), and X-ray microanalysis. Deposition of calcium, partially in the form of calcium phosphate, was found at the interface. Resorption of the implant material occurred as the result of mono- and multinuclear phagocyte activity. Resorption decreased 6 mnth after the operation, possibly due to the decreasing number of phagocytes at the interface and the increasing amount of bone in the macropores.

Endotoxin and tumor necrosis factor-alpha in middle ear effusions in relation to upper airway infection.

OBJECTIVES/HYPOTHESIS: This study was performed to elucidate the role of endotoxin and tumor necrosis factor-alpha (TNF-alpha) in the middle ear effusions (MEEs) of children with otitis media with effusion (OME) in relation to the chronicity of the disease and the presence of upper respiratory tract infection (URTI). STUDY DESIGN: In a retrospective study 140 MEEs were collected from 101 children between 2 and 12 years of age, and evaluated for the cytokine TNF-alpha and the lipopolysaccharide endotoxin. The amounts were quantified and correlated with the type of MEE, OME duration, and the presence of URTI. METHODS: Endotoxin levels were measured using a limulus amebocyte lysate assay and TNF-alpha levels were measured with an enzyme-linked immunosorbent assay (ELISA). Means of the different variables were compared using the one-way ANOVA least significance difference test with P<.05. RESULTS: In MEEs classified as mucopurulent (22.8%) both endotoxin and TNF-alpha levels (11.9+/-3 ng/mg total protein and 61.1+/-21 pg/mg total protein, respectively) were significantly higher compared with serous- (23.6%) or mucoid- (53.6%) type effusions. Fifty-five percent of the children who were classified as having chronic OME also had significantly higher amounts of endotoxin and TNF-alpha. The majority of the children (61%) had no URTI, although children with URTI (36%) did also have significantly higher levels of endotoxin and TNF-alpha in their middle ears. CONCLUSIONS: These results indicate that there is a strong correlation between the endotoxin and the TNF-alpha concentration in the middle ear and the type of MEE, the presence of URTI, and the chronicity of the disease.

Otitis media with effusion and chronic upper respiratory tract infection in children: a randomized, placebo-controlled clinical study.

This study was performed to investigate the course of spontaneous recovery from otitis media with effusion in children with chronic rhinosinusitis treated in various ways. One hundred forty-one children between 3 and 10 years of age were selected for the presence of chronic rhinosinusitis and unilateral or bilateral otitis media with effusion. The children were assigned at random to one of four treatment groups, i.e., placebo, amoxicillin combined with xylometazoline hydrochloride nose drops, maxillary sinus drainage, or a combination of the latter two forms of therapy. The follow-up period was 6 months. Drainage of the maxillary sinus had no effect on either the recovery of the chronic upper respiratory tract infection or otitis media with effusion. Amoxicillin combined with xylometazoline nose drops had no significant effect on recovery from the upper respiratory tract infection, but did have a small but significant effect on recovery from otitis media with effusion. However, the general tendency of the upper respiratory tract and ears to recover was poor. Persistence of the chronic upper respiratory tract infection during the follow-up period proved to be a negative prognostic factor with respect to cure of otitis media with effusion. Children with chronic rhinosinusitis as defined in this study appear to have a high risk of developing chronic otitis media with effusion. The results of the study are discussed.

The importance of human cochlear anatomy for the results of modiolus-hugging multichannel cochlear implants.

HYPOTHESIS: The fact that the anatomy of the basal turn of the human cochlea, especially, is essentially different from that of other species is likely to influence the outcome of cochlear implantation. BACKGROUND: Multichannel cochlear implants give better speech understanding than single-channel devices. They are intended to make use of the tonotopic organization of the cochlea by selectively stimulating subpopulations of the auditory nerve. At higher stimulus levels and with monopolar stimulation, excitation of nerve fibers from other turns may interfere with this concept, especially with modiolus-hugging electrodes. METHODS: A three-dimensional spiraling computer model of the human cochlea, based on histologic data, was used to test the spatial selectivity and the dynamic range before cross-turn stimulation takes place for the Clarion HiFocus implant with and without a positioner. The results were compared with a similar model of the guinea pig cochlea. RESULTS: In humans (in contrast to the guinea pig), a well-designed modiolus-hugging electrode yielded reduced current thresholds and high spatial selectivity without reduction of the useful dynamic range. The apical turn of the human cochlea, however, is largely comparable in this respect with the guinea pig cochlea, where cross-turn stimulation reduces the dynamic range substantially. CONCLUSION: The clinical success of cochlear implantation in humans and the favorable results with modiolus-hugging devices depend on the anatomy of the human cochlea.

Lipopolysaccharide concentration and bone resorption in cholesteatoma.

HYPOTHESIS: There is a relationship between the local lipopolysaccharide (LPS) concentration in cholesteatoma and local bone resorption in chronic otitis media (COM) with cholesteatoma. BACKGROUND: During the past decade, it has become known that the recruitment of osteoclasts is the main causative factor that induces bone destruction in COM with cholesteatoma. Cellular inflammation factors like cytokines may trigger the osteoclast. Sequel to this, LPS is able to up-regulate cytokines. This makes it of interest to study whether the local LPS concentration is related to bone resorption in cholesteatoma. MATERIALS AND METHODS: Twenty-four cholesteatoma samples and control tissue from COM patients without cholesteatoma were collected. During surgery, the degree of bone resorption was established and classified. Retrospectively, the authors checked whether patients had chronic purulent otorrhea. LPS concentration of the tissue samples was measured by the limulus amebocyte lysate test. The one-way analysis of variance test was used to determine the relation between LPS concentration, otorrhea, and local bone resorption. RESULTS: A significantly higher concentration of LPS was measured in samples from patients with cholesteatoma with bone resorption and otorrhea compared with cholesteatoma without bone resorption and control tissue. There were no significant differences between the LPS levels of the different groups of patients with bone resorption. CONCLUSION: It is suggested that LPS is one of the first factors in the cascade of bone resorption in COM with cholesteatoma.

Effect of HA-1A monoclonal IgM antibody on endotoxin-induced proliferation of cultured rat middle ear epithelium.

The effect of human monoclonal antibody HA-1A (Centoxin) on the effect of endotoxin on cultured rat middle ear epithelium was investigated. The addition of endotoxin to the standard culture medium revealed a concentration-related proliferative effect on cultured rat middle ear epithelium, leading to cobblestone cells, cell tracks, and stratification of epithelium, whereas rat middle ear epithelium cultured in standard medium grew as a monolayer composed of flat polygonal cells. Addition of HA-1A to standard medium supplemented with endotoxin gave rise to a statistically significant suppression of the proliferative effects of endotoxin on these cells. The morphology of rat middle ear epithelium cultured in the presence of HA-1A and endotoxin showed that these cells still had a tendency to form cobblestone-like cells and cell tracks, but to a substantially lower degree. The present results support the hypothesis that HA-1A suppresses the proliferative and morphological effects of endotoxin on rat middle ear epithelium and may play an important role in the pathogenesis of otitis media.

Cytokeratin patterns of tissues related to cholesteatoma pathogenesis.

Specimens of cholesteatoma matrix, meatal epidermis, and middle ear epithelium were removed during surgery, and immunohistochemical techniques were used to investigate cytokeratin expression. The use of five chain-specific anticytokeratin monoclonal antibodies and one broad specific anticytokeratin monoclonal antibody showed the divergent behavior of middle ear epithelium compared with the cytokeratin expression of the other two types of epithelium. Middle ear epithelium was characterized by the presence of cytokeratins 4, 8, 18, and 19, whereas in both cholesteatoma and meatal epidermis cytokeratin 10 predominated. Furthermore, cholesteatoma showed an infrequent focal presence of cytokeratins 4, 18, and 19. The similarity between cholesteatoma and meatal epidermis with respect to morphology, and the presence of cytokeratin 10 support an epidermal origin of cholesteatoma. However, a metaplastic origin cannot be excluded, because of the infrequent occurrence of a small amount of cytokeratins 4, 18, and 19 in cholesteatoma matrix that was not found in meatal epidermis but was a component of the cytokeratin pattern of middle ear epithelium.

Treatment of chronic maxillary sinusitis in children.

In the present study 141 children aged between 3 and 10 years and suffering from chronic maxillary sinusitis were treated non-selectively in one of 4 ways: amoxicillin combined with decongestive nose drops, drainage of the maxillary sinus, a combination of the two, or a placebo. The duration of the follow-up period was 6 months. The therapeutic effects of the 4 forms of treatment did not differ significantly. Haemophilus influenzae and streptococcus pneumoniae were the micro-organisms encountered most often in these children. The results are discussed.

The diagnostic value of transillumination for maxillary sinusitis in children.

In 52 children between 3 and 9 years of age drainage of the maxillary sinus was performed because of chronic purulent rhinitis and opacity of the maxillary sinuses on the radiographs. The results of preoperative transillumination were compared with the drainage findings. In this selected group of children the sensitivity of transillumination for the demonstration of congestion in the maxillary sinuses was found to be limited. The authors consider transillumination to be an obsolete method for this purpose in children.

Otitis media with effusion: disease or defense? A review of the literature.

Many studies of otitis media with effusion (OME) have been published, most of them dealing with risk factors. The literature correlates this condition with various patient characteristics and socio-economic factors, but none of these have been identified as the sole causative factor. A review of the literature suggests that otitis media with effusion is a response to pathogenic bacteria and thus a normal protective reaction of the body. Therefore, the decision on whether or not treatment is indicated should take the natural course of that response into account. In light of the literature reviewed here, we conclude that there is usually no need to treat middle ear effusion in young children.

Long-term follow-up of chronic maxillary sinusitis in children.

In 26 children, aged between 3 and 7 years, the course of therapy-resistant chronic maxillary sinusitis over a mean period of 6 years and 3 months, was analysed. The results showed that spontaneous cure had occurred in 24 of the 26 children, on average after they reached the age of 7 years. The chronic character of upper respiratory tract infections in young children is difficult to explain.

Hearing loss in very preterm and very low birthweight infants at the age of 5 years in a nationwide cohort.

In a geographically defined population of very preterm and very low birthweight infants (gestational age < 32 weeks and/or birthweight < 1500 g) hearing was evaluated in 890 children by pure-tone audiometry at the age of 5 years. Hearing loss was conductive/unspecified in 123 (13.8%) and sensorineural in 13 (1.5%) children. The prevalence of sensorineural hearing loss was 15 times as high as in 5-7 year old children in the Dutch population at large. The sensorineural hearing loss prevalence in very low birthweight and extremely low birthweight infants was similar. On account of communication disorders 10 (1.1%) children were classified as disabled and 6 (0.7%) as handicapped, following the definitions of the International Classification of Impairments, Disabilities, and Handicaps of the World Health Organisation. Children with conductive hearing loss had a higher risk of impairments, disabilities and handicaps of language and speech development, than children with normal hearing, the difference being statistically significant. The same holds for children with sensorineural hearing loss; moreover they had a significantly higher risk of impairments, disabilities and handicaps of mental development. Overall comparison of children with and without sensorineural hearing loss proved that the children with sensorineural hearing loss had a significantly less favourable outcome, based on 15 perinatal factors simultaneously. The age at which sensorineural hearing loss in very preterm and/or very low birthweight infants is detected has to be improved.

Acute otitis media. An animal experimental study.

This paper describes an investigation performed to study the middle ear events ensuing from Staphylococcus aureus induced infection in the middle ear cavity of the rat. To obtain an evaluation at both the cell and the tissue level, scanning electron microscopy, transmission electron microscopy and histology were used. Staphylococcus aureus infection appears to be characterized by five major events: (i) cellular response, (ii) humoral response, (iii) mucociliary response, (iv) fibroblastic response, (v) bony response. Since these occurrences correspond to the events witnessed in the human middle ear affected by acute otitis media, S. aureus achieved infection might prove a useful tool for the further study of this disease, by means of animal experiments.

Cytokeratin expression in cholesteatoma matrix, meatal epidermis and middle ear epithelium. A preliminary report.

The cytokeratin expression of cholesteatoma matrix, meatal epidermis and middle ear epithelium was investigated with six anticytokeratin monoclonal antibodies. One of these was broad specific and the other antibodies were directed against cytokeratins 4, 8, 10, 18 and 19 respectively. Immunoperoxidase staining of cryosections revealed the presence of cytokeratin 10 in cholesteatoma matrix and meatal epidermis. In contrast, middle ear epithelium was characterized by cytokeratins 4, 8, 18 and 19 and not by cytokeratin 10. An infrequent focal presence of cytokeratins 4, 18 and 19 was found in cholesteatoma. In general, the divergence between the cytokeratin expression of middle ear epithelium versus that of cholesteatoma and meatal epidermis suggests an epidermal origin of cholesteatoma. However, a metaplastic origin of cholesteatoma cannot be excluded because of the infrequent focal presence of cytokeratins 4, 18 and 19 in cholesteatoma.

Selective denervation of the autonomic nerve supply of the nasal mucosa.

The autonomic innervation of the nasal mucosa has been studied in normal rats and in rats in which the supplying nerves had seen selectively transected; postoperative survival times varied from 2 weeks up to 18 months. The vascular structures appeared to be innervated both by acetylcholinesterase- and noradrenalin-containing fibres. Furthermore a nerve plexus consisting of both types of fibres was observed in the subepithelial region. The nasal glands however showed only a cholinergic innervation. The pattern of the autonomic nerve supply deduced from these selective denervation experiments does not differ fundamentally from the generally accepted scheme of this system in the nose of other mammals. Denervation occurred within 2 weeks after transection of the supplying nerves, but after longer survival times reinnervation was observed.

Primary acquired and recurrent cholesteatoma versus residual cholesteatoma. A light- and electron-microscopical study.

A comparative morphological study was performed between the primary acquired and recurrent cholesteatoma on the one hand and the residual type on the other. Between these two groups of cholesteatomas, one can distinguish differences in the pathogenesis and clinical features which may have therapeutic implications. This study, based on light- and electron microscopy, revealed no essential differences in morphology between the two groups of cholesteatoma. In particular, infiltration of matrix into subepithelial tissues could be found in cholesteatoma both with and without signs of inflammation or infection in the perimatrix, and this phenomenon could be applied to both types of cholesteatoma. This morphological uniformity suggests that the differences in clinical features and pathogenesis should not influence the otologist's choice of therapeutic approach. The results of this study emphasize the importance of removing as much as possible of the adjacent subepithelial tissue during eradication of the cholesteatoma, regardless of clinical type of cholesteatoma or signs of infection.

The effect of external stimuli on cultured rat middle ear epithelium. I. Extracellular calcium concentration.

The effect of the extracellular calcium concentration on serially cultured rat middle ear epithelium was investigated with phase contrast microscopy, scanning electron microscopy, and transmission electron microscopy, as well as by a method to induce cornified envelope formation with a calcium ionophore. The results show that calcium concentration affects cell morphology and terminal differentiation. Furthermore, a role in the proliferation rate, secretory activity and migration seems likely. Since the extracellular calcium concentration may fluctuate locally during osteoresorption or osteodeposition, both of which occur during otitis media, this concentration might be an important factor in the pathogenesis of both acute and chronic otitis media.