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This prospective case review was performed with the aim to compare and asses the diagnostic values of cone-beam computed tomography (CBCT) and high-resolution computed tomography (HRCT) in the preoperative evaluation of otosclerosis. A total of 43 patients with histologically confirmed stapedial otosclerosis, who underwent unilateral stapedectomies were analyzed. Preoperative temporal bone CBCT and HRCT scans were performed in all cases. Both CBCT and HRCT imaging were characterized by a slice thickness of 0.4-0.625 mm and multiplanar image reconstruction. Histopathologic examination of the removed stapes footplates was performed in all cases. Findings of CBCT and HRCT were categorized according to the modified Marshall's grading system (fenestral or retrofenestral lesions). Histopathologic results were correlated with multiplanar reconstructed CBCT and HRCT scans, respectively. Negative control groups for CBCT (n = 36) and HRCT (n = 27) examinations consisted of patients, who underwent CBCT imaging due to various dental disorders or HRCT analysis due to idiopathic sudden sensorineural hearing loss. Histologically active foci of otosclerosis (n = 31, 72 %) were identified by both CBCT and HRCT in all cases with a sensitivity of 100 %. However, CBCT could not detect histologically inactive otosclerosis (n = 12, 23 %; sensitivity 0 %). In contrast, HRCT showed inactive otosclerosis with a sensitivity of 59.3 %. According to CBCT results, no retrofenestral lesions were found and the overall sensitivity for hypodense lesions was 61.37 %. In conclusion, CBCT is a robust imaging method in the detection of histologically active fenestral hypodense foci of otosclerosis with high sensitivity and radiologic specificity. In the light of these results, HRCT still remains the basic imaging method in the preoperative diagnosis of otosclerosis, since it has much greater sensitivity and specificity in the detection of retrofenestral hypodense lesions and histologically inactive otosclerotic foci in the oval window niche.

OBJECTIVES To establish a mathematical model of middle ear gas pressure regulation and to discuss potential implications for pathophysiology-oriented theoretical approach to middle ear surgery, with particular attention to mastoid obliteration. BACKGROUND Numerous studies support that small mastoid volume is associated with cholesteatoma. Latest studies show that mastoid obliteration is an effective technique to lower the recurrence rate in these ears. METHODS A mathematical model was used to predict the development of gas pressure balance in the function of different middle ear volumes (VME), considering normal and dysfunctional Eustachian tube. Published data as gas pressure input values and our 3D CT reconstruction data in healthy and pathologic middle ears of children were applied. RESULTS The model predicted ≤6.66 daPa pressure fluctuations in VME ≥3 ml, compared to ≥16 daPa of a VME ≤1 ml at perfect ET function, because of the different pressure change rate and pressure buffer effect of the MEs. Substantially larger fluctuations can be expected in a VME

Microbial biofilms have been implicated in the pathogenesis of chronic rhinosinusitis with nasal polyposis (CRSwNP). Intranasal application of corticosteroids (INCS) is a reliable option in the management of CRSwNP. INCS medication has been suspected to influence the presence and thickness of microbial biofilms and inflammatory cell patterns in CRSwNP. Two series of identical nasal polyps obtained from non-allergic patients with CRSwNP (n = 56), who underwent endoscopic sinus surgery (ESS), were processed to hematoxylin–eosin (H.E.) and Gram staining, respectively. Patients were recruited into three groups. Group A (n = 21) consisted of patients with continuous preoperative INCS treatment. In group B (n = 17), patients were never treated by INCS, while in group C (n = 18) INCS medication was stopped at least 6 months before ESS. Biofilm positivity varied from 76.4 to 88.8 % in different subject groups. These values and average thickness of biofilms did not reach statistically significant levels (Mann–Whitney’s U probe, p > 0.05) in different patient groups. In contrast, microscopic pattern and numbers of predominant inflammatory cell populations displayed obvious differences according to INCS treatment (Mann–Whitney’s U probe, p < 0.001). According to these observations, INCS treatment does not affect the presence and thickness of microbial biofilms in CRSwNP. In contrast, it has significant effects on the pattern of inflammatory cells infiltrating the subepithelial layer, which might result in beneficially altered extracellular matrix production and cytokine release.

INTRODUCTION Recent studies have reported genetic associations between with single nucleotide polymorphism (SNP) of the several genes of the renin-angiotensin-aldosterone (RAA) system in otosclerosis without the confirmation of RAA system expression in human stapes footplates. There are conflicting results. These results are conflicting because RAA system expression has been attributed exclusively to neural, vascular, and renal tissues, exclusively. MATERIALS AND METHODS Ankylotic stapes footplates (n = 20), cortical bone fragments (n = 10), and human kidney tissue specimens (n = 10) were processed to hematoxylin-eosin (HE) staining and RAA system-specific immunofluorescent assay (IFA), respectively. RESULTS Histologic diagnosis of otosclerosis was established in all ankylotic stapes footplates. Histologically active- (n = 13) and inactive (n = 7) foci of otosclerosis were consequently characterized by negative immunoreactions for renin, angiotensin converting enzyme (ACE), angiotensin-II (AT-II), and angiotensin-II receptor (AT-IIR), consequently. In cortical bones, a considerable RAA system expression was observed confirmed in the perivascular bone marrow progenitor cells. Kidney specimens, applied as positive controls, showed intense RAA system-specific immunoreactions. CONCLUSION Concerning current observations, the 4 studied members of RAA system that did not display active expression were not expressed at protein level in otosclerotic stapes footplates. This phenomenon was independent from the histologic activity of otosclerosis. Between these conditions, the etiologic role of RAA system is questionable in the pathogenesis of otosclerosis.

Otosclerosis is a unique osseous remodeling disorder of the human temporal bone, which is also considered as a disease of measles virus-associated inflammatory-autoimmune reaction against the middle layer of the otic capsule: globuli interossei. Its preoperative diagnosis is rather difficult, and there is no consensus-based diagnostic protocol with enough high sensitivity and specificity for the clinical confirmation of the disease. On the other hand, the preoperative diagnosis or clinical diagnosis of otosclerosis was potentially important considering several differential diagnostic-, prognostic-, and legal-ethical factors and problems. At this time, combination of various well-defined and new preoperative diagnostic methods might serve a strong clinical suspicion for otosclerosis. This fact might provide the basis of diagnosis and helps to avoid unnecessary stapes surgeries, serious intraoperative complications, and “blinded surgeries”: explorative tympanostomies that are unacceptable for most of the patients with conductive hearing loss. In this chapter, an overview is provided about the potential preoperative diagnostic tools and their specificity and sensitivity levels in case of otosclerosis or non-otosclerotic stapes fixations. Finally, authors recommend a considerable preoperative diagnostic protocol for the confirmation or exclusion of otosclerosis.

The main goal of this report is to review our current knowledge about the etiopathogenesis of otosclerotic bone remodeling disorder focusing on measles virus infection. Otosclerosis is a disease of pathologically increased bone turnover of the human otic capsule; however, the etiopathogenesis remained unclear. Persisting measles virus infection, genetic predisposition, disturbed bone metabolism, inflammatory processes, autoimmunity, and hormonal and environmental factors also may play contributing roles in the pathogenesis of otosclerosis. In the future, prospective studies based on comprehensive histopathologic, molecular biologic, and genetic analysis are necessary to get further information about the background of disease in order to clarify the role of measles in the etiopathogenesis and to find the most promising treatment option.

To estimate the correlations between high-resolution computed tomography (HRCT) scans, preoperative audiometric findings and histopathologic results in stapes ankylosis.Retrospective case review.Tertiary referral center.A total of 57 patients with stapes ankylosis, who underwent unilateral stapedectomies were analyzed.Diagnostic and therapeutic.Preoperative HRCT examinations were performed in all cases. Findings of HRCT were categorized according to Marshall's grading system. Preoperative air-bone gaps (ABGs) and bone conduction (BC) thresholds were determined. Stapes footplates removed surgically were processed using hematoxylin and eosin staining.Active otosclerosis (n = 29) was demonstrated by HRCT with a sensitivity of 76.31%, whereas its sensitivity to establish inactive otosclerosis (n = 13, 61.9%) and nonotosclerotic stapes fixations (n = 15, 51.7%) was much lower. Nonotosclerotic stapes fixations were characterized by pure conductive hearing loss that was not associated with HRCT findings. HRCT grades showed statistically significant association with BC levels at the averages of 0.5-1-2 kHz frequencies in the group of ears with inactive otosclerosis, exclusively (p0.05).HRCT is a reliable imaging method in the preoperative diagnosis of different types of stapes fixations. Imaging findings should be evaluated together with clinical history and audiometric data for obtaining as precise diagnosis for stapes fixation as possible.

Objectives/Hypothesis: Biofilms might play a potential role in the pathogenesis and high recurrence rate of chronic rhinosinusitis with nasal polyposis (CRSwNP). Biofilm persistence has been thought to correlate with epithelial damage, subepithelial inflammatory cell infiltration, and tumor necrosis factor-α receptor (TNFR) expression in CRSwNP. Study Design: Case-control experimental study. Methods: A total of 36 patients with CRSwNP undergoing endoscopic sinus surgery were analyzed. The negative control group consisted of eight patients undergoing septoplasty for nasal obstruction without CRSwNP. The nasal polyps and inferior turbinate mucosa samples applied as negative controls were processed by hematoxylin-eosin (HE) and Gram staining and TNFR-I and TNFR-II–specific immunofluorescent assay. Results: Biofilm was detected in 29 of 36 patients with CRSwNP and in none of the eight negative controls. Staining by HE showed strong correlation with the results of Gram staining protocol. In the biofilm-positive cases, TNFR-I and TNFR-II displayed homogeneous pattern of significantly increased epithelial expression compared to the biofilm-negative nasal polyps. In cases of biofilm absence, the expression pattern of TNF-α receptors was characterized by increased TNFR-II–specific immunoreaction. It was found that biofilm detectability corresponded to the integrity of nasal epithelium and to the dominant inflammatory cell type of the subepithelial layer. Conclusions: Persisting biofilms might increase the epithelial sensitivity against TNF-α that result in epithelium destruction. Coexistence of biofilms and increased TNFR expression might explain the inflammatory mucosal changes, functional disorders, and therapy resistance featuring CRSwNP. Laryngoscope,, 2012

Objectives/Hypothesis: Since the concept of tinnitus dopaminergic pathway emerged, studies have been proposed to investigate if dopaminergic agents influence tinnitus. We hypothesized that pramipexole, an agonist on D2/D3 receptors, may antagonize tinnitus in the presbycusis patients (in the frequency range of 250 to 8,000 Hz) in a dose schedule accepted for the treatment of Parkinson's disease in elderly people. Study Design: We designed a randomized, prospective, placebo-controlled and double-blind trial. Methods: Forty presbycusis patients aged 50 years or older with subjective tinnitus were randomized to two groups (20 patients in both). Patients in the drug group took pramipexole over a period of 4 weeks according to a treatment schedule as follows: week 1, 0.088 mg t.i.d.; week 2, 0.18 mg t.i.d.; week 3, 0.7 mg t.i.d.; week 4, 0.18 mg t.i.d. over 3 days and 0.088 mg t.i.d. the rest of the week. Patients in the second group received placebo. Determination of subjective grading of tinnitus perception, the tinnitus handicap inventory (THI) questionnaire and electrocochleography (ECOG) examinations served as the end points. Subjective audiometry was used to produce secondary data. A significant improvement in tinnitus annoyance is found in the group treated with pramipexole versus placebo with respect to inhibition of tinnitus and a decrease of tinnitus loudness greater than 30 dB. However, neither ECOG nor subjective pure-tone threshold audiometry revealed any change in hearing threshold in response to either pramipexole or placebo. Conclusions: Pramipexole is an effective agent against subjective tinnitus associated with presbycusis at a dose schedule used for the treatment of Parkinson's disease. The drug did not change hearing threshold. Laryngoscope, 2011

There is no significant difference in speech recognition scores obtained with the Vibrant Soundbridge and the open-fit hearing aid. However, the Vibrant Soundbridge may be superior to open-fit hearing aids in improving hearing at high frequencies (4-8 kHz).To assess whether an improvement in speech recognition conferred by Vibrant Soundbridge is more marked than that afforded by open-fit hearing aids in patients with sloping high frequency sensorineural hearing loss (SNHL).This study had a self-control prospective design. Seven patients aged 21-62 years with sloping high frequency SNHL were recruited into the study. Each patient received a Vibrant Soundbridge middle ear implant (Vibrant MED-EL) and wore an open-fit hearing aid (Danavox, DOT 10). Speech recognition tests were performed according to protocols suggested by árpád Götze's speech definition test in Hungarian language. In the first session, conventional hearing thresholds (unaided pure tone thresholds) were measured. In the second session, the aided sound-field threshold, speech understanding score and functional gain obtained using middle ear implants and open-fit hearing aids were determined after programming of the devices.Regarding speech recognition scores, there were no significant differences between data obtained with the middle ear implant and those with the open-fit hearing aid.

OBJECTIVE To characterize the pneumatization of the temporal bone in age-matched healthy children and in children with otitis media with effusion (OME). STUDY DESIGN Prospective case-control study. SETTING Tertiary hospital center. PATIENTS This study included 40 healthy children and 56 children with OME, with age ranging from 2 to 18 years. INTERVENTION Mastoid volume and surface determination by 3-dimensional reconstruction of axial temporal bone computed tomographic images. MAIN OUTCOME MEASURE Mastoid volume and surface area comparison of healthy children and children with OME. RESULTS The mastoid cell system (MCS) grows continuously up to the age of 18 years, with different intensities. The mean ± SD MCS volume and surface of children with OME are significantly lower (2.82 ± 1.51 ml and 40.45 ± 18.14 cm, respectively) than those of healthy children (10.05 ± 5.3 ml and 84.47 ± 37.95 cm, respectively). The mastoid volume and surface area of the left and right ears correlate well in healthy children. In children with bilateral OME, the ipsilateral and contralateral ears can be largely different. The ratio of surface and volume is constant in age groups. CONCLUSION In children with OME, the functional volume of MCS acting as a pressure buffer and the surface area serving for gas exchange are small. In case of OME, 1 ear could be more seriously affected by the disease. Otitis media with effusion presumably has a negative effect on the mastoid pneumatization process. The surface-to-volume ratio is constant through chronological age and is a good indicator of a normal middle ear function.

Objectives To review our current knowledge of the etiopathogenesis of otosclerotic bone remodeling including genetics, viral infection, autoimmunity and inflammation and to discuss disease pathogenesis with relevance for pharmacotherapy. Systematic review methodology Relevant publications on the etiopathogenesis, molecular biology, genetics and histopathology of otosclerosis from 1984 to 2009 were analyzed. Results and conclusions Otosclerosis is a bone remodeling disorder of the human otic capsule, however, the etiopathogenesis remains unclear. Genetic predisposition, disturbed bone metabolism, persistent measles virus infection, autoimmunity, hormonal and environmental factors also may play contributing roles in the pathogenesis of otosclerosis. Since, diagnosis of otosclerosis is still based on histopathological examination of the removed stapes footplate, systemic prospective studies based on comprehensive histopathological and molecular biological analysis are necessary to get further information about the background of disease.

To characterize the groups of middle ear effusions (MEE) defined on the basis of the ratio of albumin and immunoglobulin G concentrations (A/G) in the effusion and to identify the correlation between these groups of MEE and the clinical features of otitis media with effusion (OME).A laboratory analysis of 88 samples of MEE and a retrospective analysis of the medical history of all patients was performed.Tertiary referral center.Thirty-three girls and 23 boys with OME were included in the study.The concentrations of albumin, immunoglobulins (IgG, IgA, and IgM), complement factors (C3, C4), and C-reactive protein were determined by means of nephelometry. Enzyme-linked immunosorbent assay was used to measure cytokines interferon-gamma, tumor necrosis factor alpha, interleukin (IL)-4, and IL-10 concentrations. Groups were defined according to A/G ratio in the effusions. Thirty-five children underwent allergy testing.Two groups of MEE could be recognized on the basis of A/G ratio; the ratio was lower than 0.7 in group A and was higher than 0.7 in group B.Increased levels of interferon-gamma and tumor necrosis factor alpha were observed in group A, whereas IL-4 and IL-10 were dominating in group B. No association was found between the MEE groups and the clinical features of the disease or the atopic status of the patient.These results suggest that various groups of OME can be categorized according to the differences in A/G ratio in the effusions. These differences can reflect the variances in the pathomechanism of the development of the effusion, the stage of the disease, or the clinical background of the patients.

A 25-year-old woman who developed transient neurological abnormalities after scuba diving is reported. The subsequent day she experienced transient left-side monocular blindness. Arterial ocular occlusion in apparently healthy young women is unusual, and a search for the cause of this devastating vascular event is mandatory. Occlusion of the left branch retinal artery, total occlusion of the left internal carotid artery, and a petrous apex epidermoid were found, together with a shortened prothrombin time (INR: 0.73), a slightly elevated serum cholesterol level (6.1 mmol/l) and combined thrombophilia (elevated FVIIIC plus type 2 sticky platelet syndrome). This case underlines the complex mechanism of thromboembolic diseases, and the importance of the acquired trigger (in the present case scuba diving) in addition to the long-term anatomical and biochemical risk factors.

Hypothesis: Persistent measles virus infection of the otic capsule is suggested to be an etiologic factor in otosclerosis. Otosclerosis is a disease of complex unknown etiology causing progressive conductive and/or sensorineural hearing loss (HL). Background: Diagnostic methods of otosclerosis are sensitive to ossicular chain fixation with low specificity for otosclerotic stapes ankylosis. Methods: Nucleic acid was extracted from stapes footplates of clinically stapes fixation patients (N = 213). Measles virus nucleoprotein RNA was amplified by reverse-transcriptase polymerase chain reaction. Amplification results were correlated to histologic findings in 49 cases. Antimeasles IgG levels of all clinically stapes fixation as well as control sera specimens were measured by enzyme-linked immunosorbent assay. Results: Among clinically stapes fixation patients, 141 stapes footplates contained measles virus RNA. Among 49 histologic specimens, viral RNA was detectable only in histologically otosclerotic stapes footplates (n = 35). Histology for virus-negative footplates (n = 14) excluded otosclerosis. Antimeasles IgG levels were significantly lower in the sera of patients with virus-positive stapes than in control sera. Conclusions: Combination of decreased antimeasles IgG serum level and conductive HL has a great specificity and sensitivity as a diagnostic method in the preoperative evaluation of ossicular chain fixations otosclerosis. Low antimeasles IgG level indicates otosclerosis, whereas high level suggests nonotosclerotic ossicular chain fixations. Preoperative elucidation of the cause of a conductive HL may suggest optional medical treatment in preference to surgical methods.

The aim of the present work was to study whether neurotoxicity produced by cisplatin modified tissue insulin sensitivity in guinea-pigs. One week after selective sensory denervation of the anterior hepatic plexus by means of perineurial 2% capsaicin treatment, hyperinsulinaemic euglycaemic glucose clamp were performed to estimate insulin sensitivity in male guinea-pigs. The guinea-pigs underwent regional sensory denervation of the anterior hepatic plexus exhibited insulin resistance, whereas systemic capsaicin desensitization increased insulin sensitivity. Intraportal administration of l -nitro-arginine methyl esther (L-NAME decreased, whereas capsaicin increased insulin sensitivity. Neither atropine nor acetylcholine produced any significant effect. In animals with preceding regional capsaicin desensitization, none of the pharmacological maneuvers modified the resulting insulin resistant state. Cisplatin pretreatment induced sensory neuropathy and decreased insulin sensitivity. Insulin sensitivity did not change after either regional or systemic capsaicin desensitization in the cisplatin-treated animals. CGRP8–37, a nonselective calcitonin gene-related peptide (CGRP) antagonist (50 μg/kg i.v.), significantly increased insulin sensitivity in normal animals but only a tendency to insulin sensitization was seen after cisplatin treatment. Cisplatin treatment, similar to regional capsaicin desensitization of the anterior hepatic plexus, produced a significant decrease in insulin-stimulated uptake of 2-deoxy- d [ l- 14C] glucose in cardiac and gastrocnemius muscle with no effect on percentage suppression of endogenous glucose production by hyperinsulinaemia. We conclude that the majority of cisplatin-induced insulin resistance is related to functional deterioration of the hepatic insulin sensitizing substance (HISS) mechanism.

Hypothesis Persistent measles virus infection of the otic capsule is presumed to be one of the etiologic factors in otosclerosis. The viral pathogenesis of otosclerosis could be established only by correlative analysis: histologic examination of the stapes footplates and reverse-transcriptase polymerase chain reaction amplification of the viral RNA. At present, histologic analysis of the removed stapes footplates is the only appropriate method of distinguishing otosclerotic and nonotosclerotic stapes fixations. Background The presence of measles virus was shown in otosclerotic patients by reverse-transcriptase polymerase chain reaction amplification of the viral RNA and detecting the viral proteins by immunohistochemistry. Methods Nucleic acids (mRNA, vRNA, and DNA) were extracted from ankylotic stapes footplates of stapes fixation patients (n = 44). Measles virus genomic nucleoprotein RNA was amplified by seminested reverse-transcriptase polymerase chain reaction. Amplification results were correlated to postoperative histologic findings. Results Measles virus RNA was detectable only in histologically otosclerotic stapes footplates (n = 32). Histology for virus-negative footplates (n = 12) excluded otosclerosis. Virus-negative stapes footplates showed annular calcification (n = 8), bone resorption with increased numbers of hemosiderophages (n = 2), and mononuclear cell infiltration with osteolysis (n = 2). Conclusion Stapes ankylosis is a heterogenous disease causing conductive hearing loss with different causes. Nonotosclerotic stapes fixations may belong to degenerative disorders with variable histopathology. Otosclerosis is an inflammatory disease resulting from persisting measles virus infection of the otic capsule.

Hypothesis: Otosclerosis is a disease of unknown etiology causing conductive or sensorineural hearing loss. Persistent measles virus infection of the otic capsule is considered to be one of the etiologic factors in otosclerosis. Background: Determinants of measles virus infection and reactive inflammation were studied in otosclerosis. The presence of measles virus was shown in otosclerotic patients by reverse-transcription polymerase chain reaction (RT-PCR) amplification of the viral RNA. No report is available, however, on the types and features of paracrine cytokines in otosclerosis. Methods: Nucleic acid was extracted from stapes footplate samples of clinically otosclerotic patients. Measles virus nucleoprotein RNA was amplified by seminested RT-PCR. Tumor necrosis factor (TNF)-alpha mRNA expression was detected by RT-PCR in otosclerotic bone and was correlated with preoperative audiologic findings and measles virus positivity. Results: Among 154 clinically otosclerotic patients, 99 stapes footplate specimens contained measles virus RNA. TNF-alpha mRNA was detectable in 88 virus-positive and in 6 virus-negative stapes footplates. There was no detectable TNF-alpha mRNA expression in virus negative cases. Conclusion: The etiologic role of measles virus in the pathogenesis of otosclerosis should be considered. Detection of TNF-alpha mRNA demonstrates activated osteoclast functions and inflammatory pathways in otosclerotic stapes footplates associated with measles virus presence. Virus-associated and virus-negative pathomechanisms of otosclerosis should be distinguished.

Objective To test the application of the nerve-muscle pedicle (NMP) technique for selective reinnervation of previously denervated posterior cricoarytenoid (PCA) muscle. Methods The left recurrent laryngeal nerve (RLN) was severed in 5 mongrel dogs, and an ansa cervicalis-sternohyoid muscle pedicle was sutured to the left PCA muscle. Three dogs underwent a sham operation. Videolaryngoscopy was performed, and electromyographic data were collected after 1 year on average. Finally, histologic analysis of the NMP was performed. Results The video records showed the return of mobility of the PCA muscle reinnervated by the NMP. EMG data as to show evoked polyphasic potentials showed also evidence of reinnervation of the PCA muscle. With immunohistochemical reaction (antineurofilament antibody+biotin) we could show neurofilaments and motor endplates in both sides in all 5 animals. Conclusions The NMP technique could eliminate the need for arytenoidectomy and laterofixation in patients with unilateral or bilateral vocal fold paralysis. The quality of life and voice may be improved.

To determine whether chronic suppurative otitis media may cause sensorineural hearing loss.The files of 121 patients with unilateral chronic suppurative otitis media were reviewed in a retrospective study. Air conduction and bone conduction threshold averages were calculated over the speech frequencies (500 Hz, 1,000 Hz, and 2,000 Hz). Thresholds at 4 kHz were examined separately but in a similar way. Multiple linear regression models were used to clarify the relationships between sensorineural hearing loss and chronic otitis media.Chronic suppurative otitis media was seen to be associated with sensorineural hearing loss. When age and normal side were corrected for, pure-tone threshold and bone conduction threshold at either the speech frequencies or at 4 kHz increased gradually according to the duration of the chronic suppurative otitis media. The threshold shift was more accentuated as age increased. The sensorineural hearing loss at 4 kHz seemed to be higher than that at the speech frequencies.The inner ear is vulnerable against chronic suppurative otitis media. Older age increases this vulnerability. The proximity of the sensory cells to the potential source of harm (inflamed middle ear) may mean higher exposure, as reflected by the fact that sensory cells processing higher frequencies are more seriously damaged.

There are a number of well-known stimulation methods for the investigation of the central projection of the vestibular system. In addition to optokinetic, galvanic and neck vibration tests, the most widespread method is caloric stimulation. These listed methods cause not only vestibular, but also other effects on the central nervous system (CNS) (acoustic, tactile and nociceptive). In this paper, positron emission tomography (PET) was used to investigate whether caloric stimulation contains a non-vestibular (extravestibular) component, which would cause a distortion in the cortical activity and therefore in the vestibular effect on the CNS. Caloric stimulation was carried out in six patients who had been operated on due to cerebello-pontine angle tumour. These patients suffered post-operatively from a complete lesion of the vestibular system and anacusis on the operated side. Ipsilaterally activated areas were the inferior pole of the post-central gyrus and temporoparietal junction, caudal part of the post-central gyrus (SI, SII), inferior parietal lobule and medial frontal gyrus. Contralaterally activated areas were the anterior cingulate gyrus, medial frontal gyrus, posterior part of the insula, post-central gyrus and temporoparietal junction (SII). Ipsilaterally deactivated areas were the caudal and cranial part of the medial occipital gyrus (V2, V3, V4, V5). Contralaterally deactivated areas were the lingual gyrus, inferior occipital gyrus (V2, V3) and fusiform gyrus. On the basis of these data, it was postulated that, during caloric stimulation, extravestibular reaction also occurs, which corresponds to the subjective feeling of heat and pain. The deactivation of the occipital cortex due to an extravestibular effect was demonstrated. This is the first observation to suggest the possibility of nociceptivevisual interaction.

Evaluation of voice quality parameters of esophageal speech in different neoglottis forms after total laryngectomy.Presentation of voice analysis of 20 patients, who underwent total laryngectomy. The success of acquiring this technique was estimated by means of a voice analyzing program (pitch, sound-holding, loudness, spectrogram),and by the intelligibility via the telephone. Shape of the different types of neoglottis that developed and its functioning during vocalization and continuous speech were observed by nasal endoscopy. Data obtained from the voice analysis were compared among the observed three different neoglottis forms.The average dysphonia index of the 20 patients was 1.67 ± 0.38 (mean ± SD). Nasal fiberoscopic examination revealed three different types of neoglottis forms – a small mucosal button, two mucosal battens, and a mucosal lip. Voice quality of the esophageal speech of the patients with the mucosal button was found to be the closest to normal by subjective and objective acoustical evaluation.These findings emphasize the importance of the proper wound closure technique which can facilitate the development of a special button shape neoglottis form and help to acquire esophageal speech with the best quality parameters shortly after total laryngectomy.

Twenty temporal bones (TBs) were removed from autopsy cases and prepared for immunohistochemical examination. Ten TBs were free of ear disease whereas the other ten TBs showed the signs of chronic otitis media. Expression of markers for monocyte-macrophages (25F9, 27E10) and natural killer cells (anti-Leu-11) was examined immunohistochemically. There were no specific positive stainings with 25F9 or anti-Leu-11 antibodies in any of the specimens. Staining for 27E10 was found to be negative in each section obtained from normal cochlea. However, 27E10 positivity was detected in three of ten TBs with signs of chronic ear inflammation. This positivity can be explained by two theories: (1) activated monocytes can enter the inner ear from the systemic circulation as a consequence of chronic antigen challenge; (2) mesothelial cells could become activated as a result of a cross-reaction, with resultant positivity. Development of sensorineural hearing loss in some cases of chronic otitis media may be due to these immunological reactions.

Hintergrund und Fragestellung. Die Verbreitung der funktionellen bildgebenden Verfahren eroffnete neue Moglichkeiten bei den vestibularen Forschungen. Obwohl die zerebrale Projektion des Systems von mehreren Verfassern untersucht wurde, werfen die aus den Beschreibungen sich ergebenden Unterschiede weitere Fragen auf. In unserer Publikation stellen wir unsere mittels Positronen-Emissions-Tomographie (PET) erhaltenen Ergebnisse bei gesunden, rechtshandigen Personen dar. Patienten und Methodik. Bei allen Personen wurden rechts- und linksseitige kalorische Prufungen durchgefuhrt (n=6). Die ausgearbeitete Methode kann als eine Standardmethodik angesehen werden, die eine Moglichkeit schafft, aus verschiedenen Forschungsinstituten stammende Untersuchungsergebnisse zu vergleichen. Wir publizieren detaillierte Karten uber die infolge der angewendeten vestibularen Stimulation auftretenden Veranderungen (Gehirnaktivierung: Zunahme der regionalen Blutdurchstromung, bzw. Gehirndeaktivierung: Abnahme der regionalen Blutdurchstromung). Ergebnisse. Die aktivierten Hirnareale stimmen z. T. mit Daten von anderen Forschern uberein. Wir heben aber die Aktivitatszunahme in der Region Brodmann 6 hervor, als eine kortikale Offenbarung der unwillkurlichen isometrischen Skelettmuskulaturspannung. Hinsichtlich der Abnahme der Blutdurchstromung haben wir zahlreiche, bisher nicht beschriebene Regionen gefunden. Schlussfolgerungen. Unter den beschriebenen Regionen mit verminderter Durchblutung mochten wir auf die funktionelle Beziehung von Hippocampus und vestibularem System aufmerksam machen, indem wir als erste eine Deaktivierung ausgewiesen haben.

Tuberculosis remains one of the most challenging infectious diseases, which rarely manifests in the middle ear cleft exclusively. Typical symptoms of tuberculosis have become more and more confusing due to the genetic evolution of different Mycobacterium species. In the diagnosis of tuberculous otitis media (TOM), clinical suspicion plays a fundamental role, when topical and/or systemic antibiotic treatment cannot lead to improvement in ear discharge and inflammation. If there is no other reason of persisting otorrhea, microbiological sampling and culturing are the subsequent steps of diagnosis. These investigations, however, have low sensitivity; therefore a canal wall-up mastoidectomy is recommended, which includes the removal of necrotic bone and multiple histological sampling from various locations. Currently, histopathological analysis is the most robust and reliable method in the diagnosis of TOM. Tuberculin skin test, Mycobacterium-specific PCR and interferon-gamma release assay cannot distinguish between active, inactive or post-infective conditions. According to these considerations, these methods may serve as supplementary assays for the final diagnosis. Having the appropriate diagnosis after surgical intervention and laboratory analysis, medical management should be continued by anti-tuberculosis chemotherapy. Hereby, we demonstrate two cases with primary TOM and provide an overview of the literature in the light of diagnostic and therapeutic guidelines in the management of TOM.

Previous experiments suggested the possibility of a short-term sound stimulus-evoked and transient increase in DPOAE amplitudes. This phenomenon is possibly due to the complexity of the outer hair cells and their efferent control system and the different time scales of regulatory processes. A total of 100 healthy subjects ranging from 18 to 40 years of age with normal hearing and normal DPOAE values in the range of 781–4000 Hz were recruited in the study. Diagnostic DPOAE measurements were performed after short-term sound exposure. We proposed a 10 sec, 50 dB sound impulse as the most effective stimulus for clinical practice between 40 and 60 sec poststimulus time to detect the aforementioned transient DPOAE increase. We developed a procedure for detection of this transient increase in DPOAE by the application of a short-term sound exposure. The phenomenon was consistent and well detectable. Based on our findings, a new aspect of cochlear adaptation can be established that might be introduced as a routine clinical diagnostic tool. A mathematical model was provided that summarizes various factors that determine electromotility of OHCs and serves as a possible clinical application using this phenomenon for the prediction of individual noise susceptibility.

This retrospective case review was performed with the aim to asses the value of cone-beam computed tomography (CBCT) in the preoperative diagnosis of otosclerosis. A total of 32 patients with histologically confirmed stapedial otosclerosis, who underwent unilateral stapedectomies were analyzed. Preoperative temporal bone CBCT scans were performed in all cases. CBCT imaging was characterized by a slice thickness of 0.3 mm and multiplanar image reconstruction. Histopathologic examination of the removed stapes footplates was performed in all cases. Findings of CBCT were categorized according to Marshall's grading system (from grade 0 to grade 3). Histopathologic results were correlated to multiplanar reconstructed CBCT scans, respectively. Histologically active foci of otosclerosis (n = 21) were identified by CBCT in all cases with a sensitivity of 100 %. However, CBCT was unable to detect histologically inactive otosclerosis (n = 11, sensitivity = 0 %). According to CBCT scans, no retrofenestral lesions were found and all positive cases were recruited into the grade 1 group indicating solely fenestral lesions at the anterior pole of stapes footplates. In conclusion, CBCT is a reliable imaging method with considerably lower radiation dose than high-resolution CT (HRCT) in the preoperative diagnosis of otosclerosis. These results indicate that CBCT has high sensitivity and specificity in the detection of hypodense lesions due to histologically active otosclerosis.

Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a multifactorial disease that seems to be associated with the presence of microbial biofilms and corresponding subepithelial inflammatory reactions. Optical coherence tomography (OCT) might be applied to detect bacterial and fungal biofilms in patients with CRSwNP. A total of 27 patients with CRSwNP undergoing endoscopic sinus surgery (ESS) were analyzed. The negative control group consisted of six patients undergoing septoplasty for nasal obstruction without CRSwNP. The nasal polyps and inferior turbinate mucosa specimens applied as negative controls were processed to OCT analysis and H.E. and Gram staining. Biofilm was detected in 22 of 27 patients (81.5 %) with CRSwNP and in none of six negative controls. In our series, OCT scan showed an obvious association with the findings of H.E. and Gram staining and was allocated to be a good predictor of biofilm existence. On OCT images, biofilms were displayed as distinct superficial layers with high optical density. It was found that microscopic architecture of biofilms was strongly associated with the integrity of nasal mucosa and to the cellular pattern of subepithelial inflammatory reaction. This study confirmed the presence of microbial biofilms in patients with CRSwNP according to OCT scans and histological analysis. Since biofilms may affect the severity and recurrence rate of CRS treated by ESS they should be detected preoperatively. In conclusion, single application of OCT analysis or combination with conventional histological protocols provides a robust and reliable method for the detection of bacterial and fungal biofilms in CRSwNP. Level of evidence 3b, individual case–control study.

Objective. Adenoid hypertrophy is a common condition in childhood, which may be associated with recurring acute otitis media (RAOM), otitis media with effusion (OME), and obstructive sleep apnea syndrome (OSAS). These different clinical characteristics have some clinical overlap; however, they might be explained by distinct immunologic and infectious profiles and result in various histopathologic findings of adenoid specimens.Methods. A total of 59 children with adenoid hypertrophy undergoing adenoidectomy were studied. Three series of identical adenoid specimens were processed to hematoxylin-eosin (H.E.) and Gram staining and to respiratory virus specific real-time PCR, respectively.Results. According to the clinical characteristics, patients were recruited into three groups: RAOM (). Bacterial biofilms were detected in 21 cases, while at least one of the studied respiratory viruses was detected in 52 specimens. RAOM cases were significantly associated with biofilm existence (). In contrast, OME group was characterized by the absence of bacterial biofilm and by normal mucosa. Showing a statistically significant correlation, all OME cases were positive for human bocavirus (HBoV, ).Conclusions. Bacterial biofilms might contribute to the damage of respiratory epithelium and recurring acute infections resulting in RAOM. In OME cases persisting respiratory viruses, mainly HBoV, can cause subsequent lymphoid hyperplasia leading to ventilation disorders and impaired immunoreactivity of the middle ear cleft.

Biofilm-positive cases of chronic rhinosinusitis with nasal polyposis (CRSwNP) may form a separate clinical entity, which is characterized by high recurrence rates and resistance against different therapeutic strategies. This can be explained by a special immunologic phenotype. Biofilm existence has been supposed to correlate with increased amount of dendritic cells that are responsible for antigen presentation in CRSwNP. A total of 20 patients with CRSwNP undergoing endoscopic sinus surgery (ESS) were analyzed. The negative control group consisted of ten patients undergoing septoplasty without CRSwNP. Three series of individual nasal polyps and control specimens were processed to hematoxylin–eosin (HE) and Gram staining and to CD209-specific immunofluorescent assay, respectively. Biofilm was detected in 13 of 20 patients (65 %) with CRSwNP and in none of the ten negative controls. The subepithelial layer of biofilm-positive nasal polyps displayed a statistically significant (p < 0.001) increase in the numbers of CD209-expressing dendritic cells compared to biofilm-negative specimens. It was found that biofilm detectability showed strong correlation to the architecture of respiratory mucosa and to the dominant inflammatory cell type of the subepithelial layer. Persisting bacterial biofilms may affect the type of antigen presentation and consecutive immune reactions in the subepithelial layer of nasal mucosa. This phenomenon may result in different inflammatory pathways with specific cytokine profile compared to biofilm-negative cases. Co-existence of bacterial biofilms and dominant pattern of dendritic cells suggest a biofilm-associated immunologic phenotype in CRSwNP. This can explain the mucosal changes, functional disorders and therapy resistance featuring CRSwNP.

Objectives/Hypothesis: Microbial biofilms have been implicated in the pathogenesis of chronic rhinosinusitis with nasal polyposis (CRSwNP). Although biofilms are characterized by an extremely high resistance against chemical and physical agents, low-frequency ultrasound (LFU) treatment has been suspected to be an efficient and safe method for biofilm disruption. Study Design: Basic science experimental study. Methods: A total of 10 patients with CRSwNP undergoing endoscopic sinus surgery were analyzed. Two series of identical nasal polyps (n = 20) were processed to hematoxylin-eosin (HE) and Gram staining and to continuous-wave LFU treatment (5 minutes, 0.4 MHz, 37°C), respectively. Results: Presence of microbial biofilms was confirmed in all patients with CRSwNP. HE staining showed a strong correlation with the results of Gram protocol in biofilm detection. In the LFU-treated group (n = 10), a significantly decreased inflammatory cell count was found in the subepithelial layer of nasal polyps (P < .001). In addition, bacterial biofilms were completely removed from the surface of the epithelial layer. Microscopic tissue injuries or significant temperature changes were not detected due to LFU treatment. Conclusions: Between in vitro conditions, LFU treatment appeared to be a reliable and microscopically safe method for the disruption of microbial biofilms in CRSwNP. These results may provide a basis for a prospective human study investigating the efficacy and safety of this therapeutic modality alone or in combination with antibiotics or topical steroids in biofilm-positive cases of CRSwNP. Laryngoscope, 2013

To review our current knowledge of the pathologic bone metabolism in otosclerosis and to discuss the possibilities of non-surgical, pharmacological intervention. Otosclerosis has been suspected to be associated with defective measles virus infection, local inflammation and consecutive bone deterioration in the human otic capsule. In the early stages of otosclerosis, different pharmacological agents may delay the progression or prevent further deterioration of the disease and consecutive hearing loss. Although effective anti-osteoporotic drugs have become available, the use of sodium fluoride and bisphosphonates in otosclerosis has not yet been successful. Bioflavonoids may relieve tinnitus due to otosclerosis, but there is no data available on long-term application and effects on sensorineural hearing loss. In the initial inflammatory phase, corticosteroids or non-steroidal anti-inflammatory drugs may be effective; however, extended systemic application may lead to serious side effects. Vitamin D administration may have effects on the pathological bone loss, as well as on inflammation. No information has been reported on the use of immunosuppressive drugs. Anti-cytokine targeted biological therapy, however, may be feasible. Indeed, one study on the local administration of infliximab has been reported. Potential targets of future therapy may include osteoprotegerin, RANK ligand, cathepsins and also the Wnt-β-catenin pathway. Finally, anti-measles vaccination may delay the progression of the disease and potentially decrease the number of new cases. In conclusion, stapes surgery remains to be widely accepted treatment of conductive hearing loss due to otosclerosis. Due to lack of solid evidence, the place of pharmacological treatment targeting inflammation and bone metabolism needs to be determined by future studies.

The pathomechanism of chronic rhinosinusitis with nasal polyposis (CRS/NP) seems to be unclear. Bacterial-, fungal- and combined biofilms might play a potential role in the pathogenesis of various inflammatory diseases and recently in CRS/NP. A prospective, blinded observational study was performed to confirm that the combination of conventional hematoxylin–eosin (HE) and Gram staining protocols could be used to detect bacterial and fungal biofilms in patients with CRS/NP. A total of 50 patients with CRS/NP undergoing endoscopic sinus surgery (ESS) were analyzed. The negative control group consisted of 12 patients undergoing septoplasty for nasal obstruction without CRS/NP. The nasal polyps and inferior turbinate mucosa specimens applied as negative controls were processed to HE and Gram staining. Biofilm was detected in 44 of 50 patients with CRS/NP and in none of 12 negative controls. In our series, HE method showed an obvious correlation with the results of Gram staining and was allocated to be a good predictor of biofilm existence. It was found that the microscopic structure and thickness of biofilms were strongly associated with the integrity of nasal mucosa and with the characteristics of subepithelial cellular infiltration. This study confirmed the presence of bacterial and fungal biofilms on the surface of NPs obtained from patients with CRS. Since biofilms may affect the severity and recurrence rate of CRS treated by ESS they should be detected histologically. In conclusion, HE staining combined with Gram protocol is a robust and reliable method for the detection of bacterial and fungal biofilms in CRS/NP.

Otosclerosis is a complex bone dystrophy of the human otic capsule leading to conductive and sensorineural hearing loss. Since otosclerosis may, at least in part, be considered as an autoimmune-inflammatory disease, disturbed balance of TNF-alpha and osteoprotegerin (OPG) expression has been implicated in the pathological bone remodeling. It has been supposed that active otosclerosis is characterized by decreased or missing local OPG production with invariable OPG sensitivity of the otosclerotic foci. Ankylotic stapes footplates (n = 41) removed by stapedectomy were processed to histological examination, OPG-specific RT-PCR, tissue culturing and alkaline-phosphatase (AP) activity assessment, respectively. OPG concentration of serum specimens (n = 41) was measured by ELISA. Cortical bone fragments harvested from the external ear canal were used as negative controls of otosclerosis. Among 41 ankylotic stapes footplates, 22 active and 19 inactive otosclerosis cases were histologically diagnosed. OPG expression was significantly lower (p < 0.001) in active otosclerosis compared to inactive cases. Osteoclast cultures originated from active otosclerotic foci showed a considerable susceptibility against external OPG dosage, which resulted in a significant decrease of AP activity (p < 0.001). In contrast, OPG serum levels were in the normal range (5–100 ng/ml) indicating a non-systemic bone resorption. In conclusion, secondary decreased local OPG production might play an important role in the pathogenesis of otosclerotic bone remodeling disorder. As to previous and current results, decreased OPG sensitivity of lesion-forming cells should be excluded. These observations may indicate the potential role of recombinant OPG treatment in early stages of otosclerosis.

The objectives of our study was to review our current knowledge of the etiopathogenesis of otosclerotic bone remodeling including genetics, viral infection, autoimmunity and inflammation and to discuss disease pathogenesis with relevance to pharmacotherapy. Relevant publications on the etiopathogenesis, molecular biology, genetics and histopathology of otosclerosis from 1984 to 2009 were analyzed. Otosclerosis is a bone remodeling disorder of the human otic capsule; however, the etiopathogenesis remains unclear. Genetic predisposition, disturbed bone metabolism, persistent measles virus infection, autoimmunity, and hormonal and environmental factors also may play contributing roles in the pathogenesis of otosclerosis. Since diagnosis of otosclerosis is still based on histopathological examination of the removed stapes footplate, systemic prospective studies based on comprehensive histopathological and molecular biological analysis are necessary to obtain further information on the background of the disease.

Objective:To describe the first published case of superficial angiomyxoma with an epithelial component occurring in the retropharynx.Method:Case report of a patient with swallowing difficulties caused by a rare case of superficial angiomyxoma in the retropharynx.Results:Superficial angiomyxoma is a distinct entity among the dermal myxomatous lesions. Superficial angiomyxoma is poorly circumscribed, and local recurrence is common unless the tumour is excised with clear margins. Distinctive histological features include a myxoid mass composed of spindle and stellate-shaped cells and occasional multinucleated cells. There is prominent vasculature and a mixed inflammatory infiltrate in the stroma, particularly by neutrophil polymorphs. Epithelial structures are seen in about one-third of cases. A case of retropharyngeal tumour with morphological features of superficial angiomyxoma is reported. The tumour cells, including multinucleated ones, were negative for soft tissue differentiation markers. The inflammatory cells included lymphocytes, histiocytes and neutrophil polymorphs.Conclusion:This case demonstrates that a cutaneous type of angiomyxoma with epithelial-lined structures can occur in deep soft tissue, such as the retropharynx.

HYPOTHESIS Otosclerosis is an inflammatory bone remodeling disorder of the human otic capsule, which might be characterized by variable levels and unique expression pattern of TNF-alpha receptors. BACKGROUND Histologic characteristics of otosclerosis have been well described during the latest decades; however, the grading of different histopathologic and clinical stages has not been attributed precisely to the molecular biology of the pathologically increased metabolism of osteoclast-osteoblast axis. METHODS Forty otosclerotic- and 40 nonotosclerotic ankylotic stapes footplates (n = 80; men, 29; women, 51) were histologically analyzed: conventional hematoxylin-eosin staining and tumor necrosis factor-alpha receptor I and II (TNFRI/II)-specific immunofluorescent assay was performed. RESULTS Active otosclerosis (Grades I-II; n = 24) was featured by increased expression of TNFRII and moderate expression of TNFRI; inactive cases (Grades III-IV) were characterized by permanent expression of TNFRI; however, TNFRII-specific immunoreaction was absent. Nonotosclerotic stapes specimens showed a negligible TNFR expression. Tumor necrosis factor receptor expression pattern showed a strong correlation with the histologic activity of otosclerosis (chi2 test; p < 0.001). CONCLUSION Detection of elevated TNFR expression demonstrates activated osteoclast metabolism and inflammatory pathways in otosclerosis. Different etiopathogenesis of otosclerotic and nonotosclerotic stapes ankylosis should be distinguished. Administration of monoclonal anti-TNF-alpha antibody may be a reasonable option in the medical treatment of active stages of otosclerosis.

Objective:We report an extremely rare case of recurrent laryngeal nerve paralysis due to subclinical Lyme borreliosis.Method:Case report presenting a 15-year-old girl referred with hoarseness and soft voice.Results:Right-sided recurrent laryngeal nerve paralysis was observed using videolaryngoscopy. Imaging was used to exclude intracranial, cervical and intrathoracic embryological lesions, vascular malformations and tumours. Laboratory and electrophysiological investigations were used to exclude inflammatory and paraneoplastic processes, endocrinopathy and metabolic disorders. Serological testing was positive for Lyme disease. Parenteral ceftriaxone therapy was commenced. The patient's nerve paralysis showed complete recovery on the seventh day of antibiotic treatment; this was confirmed by videolaryngoscopy.Conclusion:Recurrent laryngeal nerve paralysis is an extremely rare complication of neuroborreliosis associated with Lyme disease. In patients with recurrent laryngeal nerve paralysis in whom the clinical history is uncertain and the usual diagnostic methods give negative results, screening with anti-borrelia immunoglobulin M is suggested.

Background: Viral respiratory infections play an important role in the pathogenesis of otitis media with effusion (OME) in children. The most common human rhinoviruses (HRVs) have been detected in middle ear effusions (MEE), but there is only limited data available about the closely related human enteroviruses (HEVs). The newly discovered human bocavirus (HBoV) has not, however, been identified in MEE of OME children. Objectives: The aim of our study was to determine the presence of HBoV and HRV/HEV and the rate of coinfection in a set of MEE samples collected from OME children. Study design: Seventy-five MEE samples from 54 children with no acute respiratory symptoms were studied with reverse transcription polymerase chain reaction (RT-PCR) for detection of HRV/HEV and quantitative PCR for detection of HBoV. Results: Twenty-six (35%) of 75 MEE samples were positive for viral nucleic acid, 22 (29%) for HEV, 10 (13%) for HRV and 2 (3%) for HBoV. There was no statistically significant difference between mucoid and serous effusions in the rate of virus detection. Forty-three percent of bilateral cases showed a contra-lateral difference in viral finding. Conclusions: Our results suggest that these common respiratory viruses can be associated with OME in children. Whether these viruses are causative etiologic factors of MEE persistence or merely remnants of previous infections is not known.

Bone destruction is a key step in the progression of cholesteatomas. Some of the lesions can grow without affecting the surrounding anatomic structures, whereas others can cause severe bone destruction despite their limited size. This study aims to identify factors that could play important role during the invasion of the disease.Cholesteatoma tissue samples were examined immunohistochemically. Tissue samples were arranged on the basis of bone destruction (destructive cholesteatomas [DC] and nondestructive cholesteatomas [NDC]). Double-immunofluorescent labeling was performed to detect simultaneously 1) tenascin (TN) and cytokeratin; 2) matrix metalloproteinase 9 (MMP-9) and TN; 3) TN and Ki-67. An in situ apoptosis detection kit was used to detect apoptotic cells. External auditory canal skin samples were used as control.1) In DCs, more widespread stromal TN labeling was seen compared with NDCs or external auditory canal skin samples. 2) More enhanced MMP-9 staining was detected in DCs compared with NDCs. 3) The proportion of Ki-67-positive cells in DC samples was significantly higher than in NDCs. 4) The percentage of apoptotic cells was higher in NDC than in DC samples.Our present study demonstrates that levels of TN, MMP-9, and proliferative activity are increased in cholesteatomas. It has also been shown that increased levels of TN, MMP-9-positive cells, and proliferative activity of the lesions, as well as decreased levels of apoptosis, can be linked to more aggressive clinical behavior of cholesteatomas. Our findings also indicate that TN and MMP-9 can be key molecules of bone destruction during cholesteatoma progression.

Hypothesis Different diseases without exact histopathologic classification can cause stapes ankylosis. Background Otosclerosis is a complex bone remodeling disorder of the otic capsule due to persisting measles virus infection and consecutive inflammatory reaction. In fact, clinical and demographic features of otosclerosis have reference to stapes ankylosis. In the clinical practice, otosclerosis and stapes ankylosis are incorrect synonyms. Methods Nonotosclerotic stapes footplates (n = 284) removed during stapedectomy were analyzed histologically. Otosclerosis was excluded during the histologic preselection (n = 437). Total RNA was extracted, and measles virus-specific reverse-transcriptase-polymerase chain reaction was performed. Results Nonotosclerotic stapes ankylosis was associated with total absence of measles virus RNA. Six main types of nonotosclerotic stapes fixations could be distinguished histologically: annular calcification (n = 152; 53.5%), globular fibrosis (n = 49; 17.25%), lymphocytic infiltration (n = 31; 10.9%), hemosiderosis (n = 22; 7.75%), granulomas (n = 17; 6%) and amyloidosis (n = 13; 4.6%). Fragmentation of nonotosclerotic stapes footplates was infrequent (7%) during stapes surgery. Only 1 floating footplate (0.35%) was reported. Conclusion Two thirds of nonotosclerotic stapes footplates represented complete pathologic bone remodeling. Unlike otosclerosis, nonotosclerotic stapes fixations were characterized by basic histopathologic findings without organ specificity that can also be identified in case of different diseases. Prevalence of nonotosclerotic stapes ankylosis is approximately 30 to 40% among stapes fixation cases. The long-term prognosis and surgical considerations theoretically differ from those of otosclerosis.

Otosclerosis is an inflammatory disease associated with persistent measles virus (MV) infection of the otic capsule. The nature of sensorineural hearing loss (SNHL) related to otosclerosis can be due to the chronic TNF-alpha release from the foci. TNF-alpha enters the inner ear fluid spaces in histologically active stages of otosclerosis and may cause outer hair cell functional disorder and subsequent SNHL without morphological changes of the organ of Corti. On the contrary, non-otosclerotic stapes ankylosis being a non-inflammatory disease is not harmful for hair cells. Theoretically, SNHL should not associate to this type of stapes fixation. Stapes footplates (N = 248) were examined by hematoxylin-eosin staining and corresponding MV-, OPG- and TNF-alpha-specific RT-PCR. Anti-measles IgG levels of serum specimens were measured by ELISA. Preoperative audiological results were correlated with otosclerotic and non-otosclerotic histopathologies. Among patients with stapes fixation, we found 93 active and 67 inactive otosclerosis, and 88 non-otosclerotic stapes ankylosis. MV could only be detected in otosclerotic stapes footplates. Audiometry revealed bone conduction threshold elevation toward the high frequencies in otosclerotic patients, which was associated to the duration of hearing loss. OPG mRNA expression was significantly lower in the TNF-alpha positive specimens, which was independent from virus positivity. In about one-third of stapes fixations, the etiology is non-otosclerotic stapes ankylosis. Histologic otosclerosis exhibits a strong correlation with MV presence in the bone as a sign of persistent MV infection and related inflammation with TNF-alpha release. This causes SNHL in the function of time. Non-otosclerotic stapes fixations do not cause high-frequency SNHL.

Otosclerosis is a bone remodeling disorder of complex etiology. Persistent measles virus infection of the otic capsule could increase the expression level of measles virus receptors (CD46) on the osteoclasts and endothelial cells of the otosclerotic foci. Presence of measles virus RNA was demonstrated in the footplates of histologically diagnosed otosclerotic patients by RT–PCR; however, no reports were available about the CD46 expression pattern and level in otosclerosis. Nucleic acid was extracted from stapes footplates of clinically otosclerotic patients (N = 116). Genomic RNA of measles virus was amplified by RT–PCR. Amplification results were correlated with postoperative histologic and CD46 specific immunhistologic findings. Among 116 stapes fixation cases, 87 otosclerotic stapes contained measles virus RNA. Histology for virus negative stapes (N = 29) represented degenerative disorders with heterogeneous histopathology. Active otosclerosis was featured by increased numbers of osteoclasts showing strong CD46 expression. In virus negative, non-otosclerotic stapes fixation and in normal stapes footplates weak CD46 immunoreaction was demonstrated on the osteocytes and fibroblasts. In otosclerosis, it is reasonable to assume that measles virus increases the expression level of its own cellular receptor. Furthermore, intensive CD46 reaction could relate to active virus replication and continuous receptor internalisation. Otosclerosis is a disease of disturbed osteoid turnover due to persistent measles virus infection and special CD46 receptor pattern of the otic capsule.

Hypothesis: Stapes ankylosis is supposed to be a disease with variable histopathology caused by otosclerosis or pseudo-otosclerosis. Persistent measles virus infection of the otic capsule could induce reactivation of quiescent embryonic osteoclasts in otosclerosis. Background: Presence of measles virus RNA was demonstrated in the footplates of otosclerotic patients by reverse-transcription polymerase chain reaction (RT-PCR). Histology of active otosclerosis is featured by the presence of numerous osteoclasts with unknown phenotype. Methods: Nucleic acid was extracted from stapes footplates of clinically otosclerotic patients (n = 261). Genomic RNA of measles virus was amplified by RT-PCR. Amplification results were correlated to postoperative histologic and CD51/61 specific immunohistologic findings. A parallel alcalic phosphatase activity assessment was performed to evaluate the metabolic activity of osteoclasts in each section. Results: Among 261 stapes fixation cases, 175 otosclerotic stapes contained measles virus RNA. Histology for virus negative stapes (n = 86) represented nonotosclerotic, degenerative disorders. Histologically confirmed otosclerosis was featured by the presence of osteoclasts with renewed, embryonic phenotype. In otosclerosis, alcalic phosphatase activity was significantly higher compared with nonotosclerotic stapes ankylosis (P < .001). Conclusion: The presence of CD51/61 positive osteoclasts in otosclerotic bone containing viral sequences provides the basis for an inflammatory bone remodeling disorder. Otosclerosis is a disease caused by persistent measles virus infection and reactivation of resting embryonic osteoclasts in the otic capsule.

Hypothesis: Otosclerosis is a bone remodeling disorder of the otic capsule causing conductive and sensorineural hearing loss. Persistent measles virus infection of the temporal bone with increased tumor necrosis factor (TNF)-alpha and decreased osteoprotegerin mRNA expression is supposed to be the main etiologic factor in otosclerosis. Background: Determinants of measles virus infection and reactive inflammation were studied in otosclerosis. The presence of measles virus was shown in otosclerotic patients by reverse transcriptase-polymerase chain reaction (RT-PCR) amplification of the viral RNA. No report is available, however, about the role and interactions of bone-specific cytokines in otosclerosis. Methods: Nucleic acid was extracted from stapes footplates of clinically otosclerotic patients. Measles virus nucleoprotein RNA was amplified by seminested RT-PCR. TNF-alpha and osteoprotegerin mRNA coexpression was detected by RT-PCR in otosclerotic bone and was correlated to measles virus positivity. Results: Among 154 clinically stapes fixation otosclerotic patients, 99 stapedes contained measles virus RNA. TNF-alpha mRNA was detectable in 88 virus-positive and in 6 virus-negative stapes footplates. Osteoprotegerin mRNA expression was significantly lower in the TNF-alpha-positive specimens (P < .0001) that was independent from virus positivity. Conclusion: Detection of TNF-alpha mRNA demonstrates activated osteoclast functions and inflammatory pathways in otosclerotic stapes footplates associated with measles virus presence. Increased expression of TNF-alpha and its action on RANK production inhibits the protective functions of osteoprotegerin on normal bone turnover in the otic capsule.

Contains fulltext : 47828.pdf (Publisher’s version ) (Closed access) Hearing impairment (HI) affects 1 in 650 newborns, which makes it the most common congenital sensory impairment. Despite extraordinary genetic heterogeneity, mutations in one gene, GJB2, which encodes the connexin 26 protein and is involved in inner ear homeostasis, are found in up to 50% of patients with autosomal recessive nonsyndromic hearing loss. Because of the high frequency of GJB2 mutations, mutation analysis of this gene is widely available as a diagnostic test. In this study, we assessed the association between genotype and degree of hearing loss in persons with HI and biallelic GJB2 mutations. We performed cross-sectional analyses of GJB2 genotype and audiometric data from 1,531 persons, from 16 different countries, with autosomal recessive, mild-to-profound nonsyndromic HI. The median age of all participants was 8 years; 90% of persons were within the age range of 0-26 years. Of the 83 different mutations identified, 47 were classified as nontruncating, and 36 as truncating. A total of 153 different genotypes were found, of which 56 were homozygous truncating (T/T), 30 were homozygous nontruncating (NT/NT), and 67 were compound heterozygous truncating/nontruncating (T/NT). The degree of HI associated with biallelic truncating mutations was significantly more severe than the HI associated with biallelic nontruncating mutations (P