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Zusammenfassung Hintergrund Infektionen der Atemwege sind die Hauptindikation für eine ambulante Antibiotikatherapie im Kindes- und Jugendalter. In den letzten Jahren ist die Antibiotika-Verordnungsrate (AVR) in der pädiatrischen Bevölkerung im Saarland deutlich zurückgegangen. Ziele und Fragestellung Ziel des retrospektiven Mastoiditis-Audits im PaedineSaar Netzwerk ist es, die Inzidenz der stationären akuten Mastoiditis (AM) im Saarland (2014–2019) im Hinblick auf die sinkende AVR bei Kindern zu untersuchen sowie Daten zum klinischen Verlauf der AM zu erheben. Methoden Es wurden alle stationären AM-Fälle (2014–2019) aus 6 Kliniken für Kinderheilkunde und/oder HNO-Heilkunde im Saarland und Trier retrospektiv ausgewertet. Patienten mit AM im Alter von 0–17 Jahren mit Wohnsitz im Saarland wurden in die Studie eingeschlossen. Ergebnisse Zwischen 2014 und 2019 wurden 53 stationär behandelte AM-Fälle erfasst. Während des Studienzeitraums gab es keinen signifikanten Anstieg der AM-Inzidenz (mittlere Inzidenz 2014–2019 6,1/100 000). 34% (18/53) der Patienten erhielten prästationär eine orale antibiotische Therapie. Mindestens eine Komplikation trat bei 30% der Patienten (16/53) auf. Es zeigte sich ein leichter Trend zu mehr Komplikationen bei Kindern ohne orale Antibiotikabehandlung vor der stationären Aufnahme (14/35 (40%) vs. 2/18 (11%) P=0,056). Diskussion Die Inzidenz der stationär behandelten AM im Saarland ist 2014–2019 trotz eines signifikanten Rückgangs der ambulanten AVR nicht gestiegen. Die Ergebnisse dieses Audits sollen zur Entwicklung eines standardisierten Vorgehens bei der Diagnostik und Behandlung von Kindern mit AM dienen.

Infections of the respiratory tract are the main indication for outpatient antibiotic therapy in children and adolescents. In recent years the antibiotic prescription rate (APR) in the pediatric population has decreased significantly.The aim of the retrospective mastoiditis audit in the PaedineSaar network is to investigate the incidence of inpatient acute mastoiditis (AM) in Saarland (2014-2019) regarding to the decreasing APRs in children, as well as to gather data of the clinical course of AM.All inpatient AM cases 2014-2019 were analyzed retrospectively from 6 hospitals for pediatrics and/or otorhinolaryngology in Saarland and Trier. Children and adolescents aged 0-17 years and residing in Saarland were included in the study.2014-2019 53 inpatient treated AM cases have been recorded. During the study period there was no significant increase of AM incidence (mean incidence 2014-2019: 6.1/100,000). 34% (18/53) of the patients received prehospital antibiotic treatment (main indication: acute otitis media (AOM) 15/18, 83%). At least one complication occurred in 30% of the patients (16/53). There was a slight trend to more complications in children without oral antibiotic treatment before admission (14/35 (40%) vs. 2/18 (11%) p=0.056).The incidence of AM leading to inpatient treatment in children in Saarland did not increase 2014-2019 despite a significant and sustained decline in the outpatient APRs. The results of this audit should be used for the development of a more standardized approach concerning the diagnostics and treatment of children with AM.Infektionen der Atemwege sind die Hauptindikation für eine ambulante Antibiotikatherapie im Kindes- und Jugendalter. In den letzten Jahren ist die Antibiotika-Verordnungsrate (AVR) in der pädiatrischen Bevölkerung im Saarland deutlich zurückgegangen.Ziel des retrospektiven Mastoiditis-Audits im PaedineSaar Netzwerk ist es, die Inzidenz der stationären akuten Mastoiditis (AM) im Saarland (2014–2019) im Hinblick auf die sinkende AVR bei Kindern zu untersuchen sowie Daten zum klinischen Verlauf der AM zu erheben.Es wurden alle stationären AM-Fälle (2014–2019) aus 6 Kliniken für Kinderheilkunde und/oder HNO-Heilkunde im Saarland und Trier retrospektiv ausgewertet. Patienten mit AM im Alter von 0–17 Jahren mit Wohnsitz im Saarland wurden in die Studie eingeschlossen.Zwischen 2014 und 2019 wurden 53 stationär behandelte AM-Fälle erfasst. Während des Studienzeitraums gab es keinen signifikanten Anstieg der AM-Inzidenz (mittlere Inzidenz 2014–2019 6,1/100 000). 34% (18/53) der Patienten erhielten prästationär eine orale antibiotische Therapie. Mindestens eine Komplikation trat bei 30% der Patienten (16/53) auf. Es zeigte sich ein leichter Trend zu mehr Komplikationen bei Kindern ohne orale Antibiotikabehandlung vor der stationären Aufnahme (14/35 (40%) vs. 2/18 (11%) P=0,056).Die Inzidenz der stationär behandelten AM im Saarland ist 2014–2019 trotz eines signifikanten Rückgangs der ambulanten AVR nicht gestiegen. Die Ergebnisse dieses Audits sollen zur Entwicklung eines standardisierten Vorgehens bei der Diagnostik und Behandlung von Kindern mit AM dienen.

Significance: Optoacoustic-induced vibrations of the hearing organ can potentially be used for a hearing device. To increase the efficiency of such a hearing device, the conversion of the light energy into vibration energy within each type of irradiated tissue has to be optimized. Aim: To analyze the wavelength-dependency of optoacoustic-induced vibrations within the tympanic membrane (TM), and to define the most efficient and best-suited optical stimulation parameters for a novel auditory prosthesis. Approach: Single nanosecond laser pulses, continuously tunable in a range of visible to near-infrared, were used to excite the guinea pig TM. The induced vibrations of the hearing organ were recorded at the malleus using a laser Doppler vibrometer. Results: Our results indicate a strong wavelength-dependency of the vibration’s amplitude correlating with the superposition of the absorption spectra of the different specific tissue components. Conclusions: We investigated the spectrum of the vibrations of the hearing organ that were induced optoacoustically within a biological membrane embedded in air, in an animal model. First applications for these results can be envisioned for the optical stimulation of the peripheral hearing organ as well as for research purposes.

Pressure sensitive adhesives based on silicone materials are used particularly for skin adhesion, e.g., the fixation of electrocardiogram (ECG) electrodes or wound dressings. However, adhesion to sensitive tissue structures is not sufficiently addressed due to the risk of damage or rupture. We propose an approach in which a poly-(dimethylsiloxane) (PDMS)-based soft skin adhesive (SSA) acts as cellular scaffold for wound healing. Due to the intrinsically low surface free energy of silicone elastomers, functionalization strategies are needed to promote the attachment and spreading of eukaryotic cells. In the present work, the effect of physical adsorption of three different proteins on the adhesive properties of the soft skin adhesive was investigated. Fibronectin adsorption slightly affects adhesion but significantly improves the cellular interaction of L929 murine fibroblasts with the polymeric surface. Composite films were successfully attached to explanted tympanic membranes. This demonstrates the potential of protein functionalized SSA to act as an adhesive scaffold in delicate biomedical applications.

Inspired by the gecko foot, polymeric microstructures have demonstrated reliable dry adhesion to both stiff objects and sensitive surfaces such as skin. Microstructured silicone patches are proposed, herein, for the treatment of tympanic membrane perforations with the aim of serving as an alternative for current surgical procedures that require anesthesia and ear canal packing. Sylgard 184 PDMS micropillars of 20 μm in diameter and 60 μm in length are topped by a Soft Skin Adhesive (SSA) MG7‐1010 terminal layer, of about 25 μm thickness. The adhesion is evaluated by specially designed tack tests against explanted murine eardrums and, for comparison, against a rigid substrate. Functional effects are evaluated using auditory brainstem responses (ABRs) and distortion product otoacoustic emissions (DPOAE). The adhesion strength of the microstructure and unstructured controls to explanted murine tympanic membranes is comparable (typically 12 kPa), but the microstructured patches are easier to handle by the surgeon. For the first time, partial recovery of hearing performance is measured immediately after patch application. The novel patches adhere without the need for further fixation, removing the need for ear canal packing. The proposed material design holds great promise for improving clinical treatments of tympanic membrane perforations.

Inner hair cell (IHC) Cav1.3 Ca2+ channels are multifunctional channels mediating Ca2+ influx for exocytosis at ribbon synapses, the generation of Ca2+ action potentials in pre-hearing IHCs and gene expression. IHCs of deaf systemic Cav1.3-deficient (Cav1.3-/-) mice stay immature because they fail to up-regulate voltage- and Ca2+-activated K+ (BK) channels but persistently express small conductance Ca2+-activated K+ (SK2) channels. In pre-hearing wildtype mice, cholinergic neurons from the superior olivary complex (SOC) exert efferent inhibition onto spontaneously active immature IHCs by activating their SK2 channels. Because Cav1.3 plays an important role for survival, health and function of superior olivary complex (SOC) neurons, SK2 channel persistence and lack of BK channels in systemic Cav1.3-/- IHCs may result from malfunctioning neurons of the SOC. Here we analyze cochlea-specific Cav1.3 knockout mice with green fluorescent protein (GFP) switch reporter function, Pax2::cre;Cacna1d-eGFPflex/flex and Pax2::cre;Cacna1d-eGFPflex/-. Profound hearing loss, lack of BK channels and persistence of SK2 channels in Pax2::cre;Cacna1d-eGFPflex/- mice recapitulated the phenotype of systemic Cav1.3-/- mice, indicating that in wildtype mice, regulation of SK2 and BK channel expression is independent of Cav1.3 expression in SOC neurons. In addition, we noticed dose-dependent GFP toxicity leading to death of basal coil IHCs of Pax2::cre;Cacna1d-eGFPflex/flex mice, likely because of high GFP concentration and small repair capacity. This and the slower time course of Pax2-driven Cre recombinase in switching two rather than one Cacna1d-eGFPflex allele lead us to study Pax2::cre;Cacna1d-eGFPflex/- mice. Notably, control Cacna1d-eGFPflex/- IHCs showed a significant reduction in Cav1.3 channel cluster sizes and currents, suggesting that the intronic construct interfered with gene translation or splicing. These pitfalls are likely to be a frequent problem of many genetically modified mice with complex or multiple gene-targeting constructs or fluorescent proteins. Great caution and appropriate controls are therefore required.

Significance: Worldwide, ∼460 million people suffer from disabling hearing impairment. Many of these patients are still not sufficiently supplied with currently available auditory technologies. Optical stimulation of the hearing organ offers a promising alternative for a new generation of auditory prostheses. Aim: To assess the biocompatibility margins of our laser pulse amplitude strategy in vitro, we designed a protocol and present the effects on normal human dermal fibroblasts, human chondrocytes, and human osteoblasts. Approach: Laser pulses of 532 nm were applied over 120 s using our laser pulse amplitude modulation strategy. We then assessed cell viability and cytotoxicity through fluorescence staining and quantitative polymerase chain reaction-analysis regarding 84 key player-genes for cytotoxicity and stress response. Results: The first in vitro biocompatibility margins for our stimulation parameters applied to cells of the peripheral hearing organ were between 200 and 223 mW (3348 J/cm2). After irradiation with a subphototoxic laser power of 199 mW (2988 J/cm2), only the fibroblasts showed a significant upregulation of GADD45G. Conclusion: Further studies are underway to optimize parameters for the optoacoustic stimulation of the auditory system. Our protocol and results on laser–tissue interactions can be useful for translational laser applications in various other irradiated biological tissues.

The tympanic membrane (TM) separates the outer ear from the tympanic cavity. Repeated pathologies can permanently decrease its tension, inducing conductive hearing loss and adhesive processes up to cholesteatoma. The current main therapy is its surgical reconstruction. Even though lasers have been proposed to tighten atrophic TMs, details of this effect, specifically histological analyses, are missing. We therefore used laser pulses to induce TM collagen remodeling in an animal model to compare the histological and electrophysiological effects of different applied laser intensities before entering clinical studies. We irradiated Fuchsin-stained areas of the TM in anesthetized mice with 532-nm laser-pulses of 10 mW for 30 s (0.3 J), 25 mW for 30 s (0.75 J) or 50 mW for 30 s (1.5 J) monitoring hearing with auditory brainstem responses (ABRs). The mice were sacrificed after 2 to 8 weeks and histologically analyzed. An increase in the TM thickness within the defined, stained, and irradiated areas could be observed after 4 weeks. Polarized light microscopy and transmission electron microscopy demonstrated the tissue volume increase majorly due to new collagen-fibrils. Directly after irradiation, ABR thresholds did not increase. We herein demonstrate a controlled laser-induced collagen remodeling within defined areas of the TM. This method might be the prophylactic solution for chronic inflammatory ear pathologies related to decreased TM tension.

Repeated pathologies of the tympanic membrane (TM) decrease its tension inducing conductive hearing loss and adhesive processes up to cholesteatoma. Our results regarding the development of a laser based noninvasive procedure to strengthen the structure of the TM are herein presented.

Hearing impairment affects ∼460 million people worldwide. Conservative therapies, such as hearing aids, bone conduction systems, and middle ear implants, do not always sufficiently compensate for this deficit. The optical stimulation is currently under investigation as an alternative stimulation strategy for the activation of the hearing system. To assess the biocompatibility margins of this emerging technology, we established a method applicable in whole-mount preparations of murine tympanic membranes (TM). We irradiated the TM of anesthetized mice with 532-nm laser pulses at an average power of 50, 89, 99, and 125 mW at two different locations of the TM and monitored the hearing function with auditory brainstem responses. Laser-power-dependent negative side effects to the TM were observed at power levels exceeding 89 mW. Although we did not find any significant negative effects of optical stimulation on the hearing function in these mice, based on the histology results further studies are necessary for optimization of the used parameters.

Artemin and its receptors are upregulated in the auditory nerve of deafened rats as a possible intrinsic protective mechanism against ototoxicity-related apoptosis. Consequently, we examined the effect of artemin on spiral ganglion neurons in vitro and in vivo. Spiral ganglion neurons were isolated from neonatal rats and cultured in serum-free medium supplemented with artemin and/or brain-derived neurotrophic factor (BDNF). In vitro, the survival rate of spiral ganglion neurons cultivated with artemin or BDNF was significantly improved compared with negative controls. In addition, artemin was delivered to the inner ear of deafened guinea pigs for 28 days. In-vivo artemin was as effective as BDNF in spiral ganglion neuron protection. Therefore, artemin promotes the survival of spiral ganglion neurons in vitro and in vivo.

Objectives: Contact endoscopy is a noninvasive tool that allows in vivo and in situ examination of superficial mucosa. Its use for early diagnosis of cancerous lesions of the oropharynx and larynx has not been evaluated. The aim of the study was to validate contact endoscopy for the examination of pharyngeal and laryngeal mucosa. Study Design: Prospective clinical study. Methods: Superficial cells of the mucosa were stained with methylene blue and examined with contact endoscopes. The documented images were assessed by a cytopathologist and by an otolaryngologist independently for each patient. Biopsies for histopathological examination of the area were performed and correlated with contact endoscopic findings of both examiners. Results: Of the 42 examined specimen, 32 (76.2%) showed benign changes in the histological analysis. Squamous cell carcinoma was revealed in 10 specimen (23.8%). Using contact endoscopy, the cytopathologist accurately identified 90.6% of the benign findings (29 of 32); however, only seven of 10 (70%) carcinomas were correctly categorized. In comparison, the otolaryngologist made a correct diagnosis in 93.75% (30 of 32) of the benign and in 90% (nine of 10) of the malignant cases. Thus, a sensitivity of 90% and a specificity of 93.75% can be achieved by contact endoscopy. Conclusions: Contact endoscopy offers valuable support for the evaluation of oropharyngeal, hypopharyngeal, and laryngeal mucosa. Contact endoscopy can be a useful contribution to rapid intraoperative evaluation of mucosal alterations for early diagnosis of tumors and might reduce diagnostic biopsy sampling. Even so, it does not replace biopsy sampling. Laryngoscope, 2010

Background Gene therapy may provide a way to restore cochlear function to deaf patients. The most successful techniques for cochlear gene therapy have been injection of early-generation adenoviral vectors into scala media in guinea pigs. However, it is important to be able to perform gene therapy research in mice because there is wide availability of transgenic strains with hereditary hearing loss. Purpose We demonstrate our technique for delivery of a third-generation adenoviral vector, helper-dependent adenovirus (HDAd), to the adult mouse cochlea. Methods Mice were injected with an HDAd that contained a reporter gene for either beta-galactosidase or green fluorescent protein into scala media. After 4 days, the cochleae were harvested for analyses. Auditory brainstem response monitoring of cochlear function was performed before making a cochleostomy, after making a cochleostomy, and before killing the animal. Results Beta-galactosidase was identified in the spiral ligament, the organ of Corti, and spiral ganglion cells by light microscopy. Green fluorescent protein epifluorescence was assessed in whole-mount organ of Corti preparations using confocal microscopy. This demonstrated transduction of inner hair cells, outer hair cells, and supporting cells. Paraffin-embedded cross sections similarly revealed gene transduction within the organ of Corti. Threshold shifts of 39.8 +/- 5.4 and 37.7 +/- 5.5 dB were observed in mice injected with HDAd or control buffer, respectively. Conclusion The technique of scala media HDAd injection reliably infects the adult mouse cochlea, including cells within the organ of Corti, although the procedure itself adversely affects hearing.

Objective: To present the preliminary results of new malleus replacement prosthesis combined with a total ossicular prosthesis in middle ear reconstruction in patients missing the malleus and stapes. Study Design: Prospective experimental and nonrandomized clinical study. Setting: Tertiary referral center. Methods: An original titanium malleus replacement prosthesis (MRP) was designed to be inserted into the external auditory canal and to replace a missing malleus for various middle ear pathologies. The MRP was tested experimentally and clinically. The vibratory properties of the new prosthesis were measured using laser Doppler vibrometry. Ninety patients with missing malleus and stapes, undergoing 92 ossicular reconstructions were enrolled in this study from September 1994 to March 2012. Comparative analyses were made between a group of 34 cases of ossicular reconstructions with total prosthesis (TORP) positioned from the tympanic membrane to the stapes footplate (TM-to-footplate assembly) and a group of 58 cases of ossicular reconstructions with TORP positioned from a newly designed malleus replacement prosthesis (MRP) to the stapes footplate (MRP-to-footplate assembly). Preoperative and postoperative audiometric evaluation using conventional audiometry, that is, air-bone gap (ABG), bone-conduction thresholds (BC), and air-conduction thresholds (AC) were assessed. Results: Experimentally, the vibratory properties of the MRP are promising and remain very good even when the MRP is cemented into the bony canal wall mimicking its complete osseous-integration, if this were to occur. This finding supports the short-term clinical results as in the TM-to-footplate group; the 3-month postoperative mean ABG was 23.3 dB compared with 12.5 dB in the MRP-to-footplate group (difference, 10.8; 95% confidence interval, 4.0-17.6); 37.0% of patients from the TM-to-footplate group had a postoperative ABG of 10 dB or less, and 48.1% of patients had a postoperative ABG of 20 dB or less, as compared with 58.1% and 79.1%, respectively, in the MRP-to-footplate group. The average gain in AC was 11.0 dB in the TM-to-footplate group as compared with 21.3 dB in the MRP-to-footplate group (difference, -10.3; 95% confidence interval, -18.2 to -2.4). Conclusion: The results of this study indicate that superior postoperative hearing thresholds could be achieved using a MRP-to-footplate assembly, compared with a TM-to-footplate assembly in patients with an absent malleus undergoing ossiculoplasty. The postoperative AC thresholds, after 3 months and 1 year, are significantly lower in patients treated with the MRP-to-footplate assembly.

Background Despite numerous studies, the tumor biology of pleomorphic adenomas, the most common salivary gland tumors, is still not completely defined. In order to identify further candidate genes important for tumor biology of pleomorphic adenomas, extended cytogenetic and molecular analysis are mandatory. Methods We performed a detailed molecular cytogenetic analysis using comparative genomic hybridization (CGH) followed by fluorescence in situ hybridization (FISH) with probes for chromosome X, 16p, 17, and 20 on a large cohort of pleomorphic adenomas (n = 29). Results We could confirm previously described deletions in pleomorphic adenomas affecting 16p, 17, 20q, and 22 by FISH and/or CGH analysis. Moreover, our CGH study revealed novel candidate regions on 8p23.1pter, 9p, 10q25.1q25.3, and 11q24qter in the series of analyzed pleomorphic adenomas. Conclusion Our present study reveals new insights in novel candidate regions implicated in pleomorphic adenoma tumorigenesis which should be considered in further molecular studies. © 2012 Wiley Periodicals, Inc. Head Neck 35: 1431–1438, 2013

The treatment of choice for profound sensorineural hearing loss (SNHL) is direct electrical stimulation of spiral ganglion cells (SGC) via a cochlear implant (CI). The number and excitability of SGC seem to be critical for the success that can be achieved via CI treatment. However, SNHL is associated with degeneration of SGC. Long-term drug delivery to the inner ear for improving SGC survival may be achieved by functionalisation of CI electrodes with cells providing growth factors. Therefore, the capacity of brain-derived neurotrophic factor (BDNF)-secreting NIH3T3 cells grown on cylindrically shaped silicone elastomers (SE) to exert local and sustained neuroprotective effects was assessed in vitro and in vivo. An in vitro model to investigate adhesion and cell growth of lentivirally modified NIH3T3 cells synthesising BDNF on SE was established. The bioactivity of BDNF was characterised by co-cultivation of SGC with cell-coated SE. In addition, cell-coated SE were implanted into deafened guinea pigs. The recombinant NIH3T3 cells proliferated on silicone surfaces during 14 days of cultivation and expressed significantly increasing BDNF levels. Enhanced survival rates and neurite outgrowth of SGC demonstrated the bioactivity of BDNF in vitro. Implantation of SE with adhering BDNF-secreting NIH3T3 cells into the cochleae of systemically deafened guinea pigs induced a significant increase in SGC survival in comparison to SE without cell coating. Our data demonstrate a novel approach of cell-based long-term drug delivery to support SGC survival in vitro and in vivo. This therapeutic strategy--once transferred to cells suitable for clinical application--may improve CI performance.

Objective: In subjects who are deaf and who also have tinnitus in the affected ear, tinnitus treatments based on acoustic input are impossible. On the other hand, tinnitus suppression using electric stimulation has been reported to be successful. Therefore, a study was initiated to investigate the potential of cochlear implantation (CI) in unilateral deaf subjects regarding tinnitus suppression, device acceptance, and restoration of spatial hearing. Method: Five subjects with severe to profound unilateral deafness having also ipsilateral tinnitus were enrolled. In monthly visits, the speech processor program was optimized, and the hearing performance as well as tinnitus were monitored. In addition, it was investigated whether the CI improves hearing in adverse listening situations when combined with the normal hearing side. Results: In 3 participants, the tinnitus was significantly suppressed while wearing the device. In the other 2 participants, the tinnitus could be reduced in certain situations. Speech perception tests revealed a significant benefit with the CI in combination with the normal-hearing side for 3 participants. All participants accepted the device in a clinical setting; adaptation of the frequency allocation was not required. Conclusion: Improvements were found regarding the hearing and the tinnitus. Not all participants benefit from the CI to the same degree and in the same situations. The results indicate that cochlear implantation in subjects with unilateral severe to profound hearing loss and ipsilateral tinnitus may be beneficial on a case-to-case basis. Further work needs to be performed to define the appropriate indication criteria. Key Words: Acoustic and electric hearingVCochlear implantVFrequency allocationVSpatial hearingVTinnitusVUnilateral deafness. Otol Neurotol 31:1381Y1385, 2010.

An acoustic transient can be generated inside an absorbing tissue as a result of laser-tissue interaction after pulsed laser irradiation. Herein we report a novel application of this physical process, the optoacoustic wave generation in the inner ear and subsequently the induction of basilar membrane vibrations. These laser induced vibrations show a direct correlation to the laser energy and an indirect correlation to the distance from the irradiation focus. Through these characteristics they may be used, in a new generation of cochlear implants, to improve the frequency specific cochlear activation and consequently improve speech perception in hearing impaired patients with residual hearing.

Contact endoscopy is a noninvasive tool that allows in vivo and in situ examination of superficial mucosa. Its use for early diagnosis of cancerous lesions of the oropharynx and larynx has not been evaluated. The aim of the study was to validate contact endoscopy for the examination of pharyngeal and laryngeal mucosa.Prospective clinical study.Superficial cells of the mucosa were stained with methylene blue and examined with contact endoscopes. The documented images were assessed by a cytopathologist and by an otolaryngologist independently for each patient. Biopsies for histopathological examination of the area were performed and correlated with contact endoscopic findings of both examiners.Of the 42 examined specimen, 32 (76.2%) showed benign changes in the histological analysis. Squamous cell carcinoma was revealed in 10 specimen (23.8%). Using contact endoscopy, the cytopathologist accurately identified 90.6% of the benign findings (29 of 32); however, only seven of 10 (70%) carcinomas were correctly categorized. In comparison, the otolaryngologist made a correct diagnosis in 93.75% (30 of 32) of the benign and in 90% (nine of 10) of the malignant cases. Thus, a sensitivity of 90% and a specificity of 93.75% can be achieved by contact endoscopy.Contact endoscopy offers valuable support for the evaluation of oropharyngeal, hypopharyngeal, and laryngeal mucosa. Contact endoscopy can be a useful contribution to rapid intraoperative evaluation of mucosal alterations for early diagnosis of tumors and might reduce diagnostic biopsy sampling. Even so, it does not replace biopsy sampling.

Gacyclidine, a non-competitive NMDA receptor antagonist, is a phencyclidine derivative with neuroprotective properties. It has been previously safely administered intravenously to acute traumatic brain-injured patients. Experiments in guinea pigs have shown that local administration of gacyclidine to the cochlea can suppress salicylate-induced tinnitus. Thus, we thought that patients with therapy-resistant sensorineural tinnitus might benefit from a local therapy with gacyclidine. As a compassionate treatment, we administered aqueous gacyclidine solution via a Durect RWmuCath(TM) into the round window niche in six patients with unilateral deafness associated with tinnitus. The response of each patient to the drug treatment was given a numerical value by the use of a visual analogue scale (VAS) on a scale of 0-10 for tinnitus intensity, where 0 represented no tinnitus and 10 represented unbearable tinnitus-intensity or -annoyance (subjective). After constant perfusion of gacyclidine for 40-63 h, four out of six patients experienced a temporary relief from their tinnitus. No serious side effects were recorded in any of the cases. Gacyclidine might present a potent drug for the suppression of sensorineural tinnitus in humans and therefore should be considered for future double-blinded, placebo-controlled clinical trials. For lasting effective treatment, controlled intracochlear and long-term delivery of the drug seems to be necessary. Further studies investigating the toxicological effects of gacyclidine intracochlear perfusion as well as different dosages and therapy durations are under way to ensure the safety of the drug for long-term human use and warrant clinical trials.

The success of conventional hearing aids and electrical cochlear implants have generally been limited to hearing in quiet situations, in part due to a lack of localized (i.e., frequency specificity) sensorineural activation and subsequent impaired speech discrimination in noise. Laser light is a source of energy that can be focused in a controlled manner and may provide more localized activation of the inner ear, the cochlea. Compound action potentials have been elicited using 2.12 µm laser pulses through activation of auditory nerve fibers (Izzo et al. 2006). Laser stimulation (813 nm) of the cochlea has shown to induce basilar membrane motion and cochlear microphonic potentials (Fridberger et al. 2006). We sought to assess if visible light (green, 532 nm, 10 ns pulses) could be used to consistently activate the cochlea. The laser parameters were selected based on our initial attempt to induce an optoacoustic effect as the energy transfer mechanism to the cochlea. Click evoked auditory brainstem responses (AABRs) were recorded preoperatively in ketamine-anesthetized guinea pigs to confirm normal hearing. The bulla and then the cochlea were exposed. Optically evoked ABRs (OABR) were recorded in response to laser stimulation with a 50 µm optical fiber (532 nm, 10 ns pulses, 500 repetitions, 10 pulses/s; Nd:YAG laser) at the round window (RW) directed towards the basilar membrane (BM). OABRs similar in morphology to acoustically evoked ABRs, except for shorter latencies, were obtained for stimulation through the RW with energy levels between 1.7-30 µJ/pulse. The OABRs increased with increasing energy level reaching a saturation level around 13-15 µJ/pulse. Furthermore the responses remained consistent across stimulation over time, including stimulation at 13 µJ/pulse for over 30 minutes, indicating minimal or no damage within the cochlea with this type of laser stimulation. Overall we have demonstrated that laser light stimulation with 532 nm has potential for a new type of auditory prosthesis that can activate the cochlea without any apparent functional damage. Further studies are needed to determine the optimal laser parameters and fiber placement locations for localized and tonotopic activation.

The association of unilateral, rapidly progressive hearing loss, tinnitus and vestibular dysfunction in combination with a contrast-enhancing mass within the internal auditory canal on MRI is suggestive of a vestibular schwannoma (VS). We report the rare finding of a HIV-associated cerebral lymphocyte infiltration, most probably malignant lymphoma, which was presumed initially to be a VS. A 36-year-old male presented with progressive unilateral hearing loss accompanied by acute, ipsilateral tinnitus. Interpreted first as sudden sensorineural hearing loss, his symptoms were treated with rheologic therapy. Ipsilateral facial palsy appeared. MRI with gadolininium disclosed a contrast-enhancing mass within the internal auditory meatus of the left side. Within five weeks an extended leptomeningeal lymphocyte infiltration evolved and the diagnosis of an underlying HIV infection was made. Unilateral, rapidly progressive hearing loss and a fast growing cerebello-pontine mass is atypical for VS and highly suspicious of malignant disease. To our knowledge we report the first case of an HIV-associated cerebral lymphocyte infiltration, mimicking a VS. In such cases the diagnostic work-up should include a HIV test.

Background and Objectives The cochlea is the part of the inner ear that transduces sound waves into neural signals. The basilar membrane, a connective tissue sheet within the cochlea, is tonotopically tuned based on the spatial variation of its mass, stiffness, and damping. These biophysical properties are mainly defined by its constituent collagen fibers. We sought to assess the effect of laser irradiation on collagen within the basilar membrane using histological analysis. Study Design/Materials and Methods Four excised guinea pig cochleae were stained with trypan blue. From these, two were irradiated with a 600 nm pulsed dye laser and two were used as controls. Collagen organization was visualized using polarization microscopy. Results Laser irradiation reduced the birefringence within the basilar membrane as well as within other stained collagen-containing structures. Larger reductions in birefringence were measured when more laser pulses were given. The effects were similar across all turns of each cochlea. Conclusions Laser irradiation causes immediate alterations in collagen organization within the cochlea that can be visualized with polarization microscopy. These alterations may affect cochlear tuning. Ongoing research is aimed at analyzing the effect of laser irradiation on cochlear function. It is conceivable that this technique may have therapeutic benefits for patients with high-frequency sensorineural hearing loss. Lasers Surg. Med. 35:174–180, 2004. © 2004 Wiley-Liss, Inc.

Problem: COUP-TFI (Chicken Ovalbumin Upstream Promoter-Transcription Factor I) is an orphan member of the steroid/thyroid nuclear receptor superfamily. It is highly expressed in the developing nervous system. Null mutant COUP-TFI mice have glossopharyngeal nerve dysfunction that compromises feeding ability and usually results in perinatal death. Surviving null mutant mice demonstrate neuronal differentiation defects, altered thalamocortical axon guidance, and apoptosis of cerebral cortical layer IV. COUP-TFI expression is also important for inner ear organogenesis. Null mutants have a shortened cochlear duct, abnormal cochlear innervation, and malformed vestibular chambers. Additionally, by P20 the organ of Corti in the basal turn has degenerated. Interestingly, the organ of Corti at the mid-modiolar region has only subtle anatomic irregularities and, in particular, contains normal-appearing inner and outer hair cells. We sought to determine the effect of this mutation on cochlear function. Methods: We recorded ABR and DPOAE thresholds in P16-18 null mutant and heterozygote COUP TFI mice, as well as age-matched wild-type controls. ABRs were evoked with a 5 msec sine wave tone pip. DPOAEs were elicited using F2 = 1.2*F1 and L2 = L1. All measurements were performed using stimuli up to 80 dB SPL over the frequency spectrum of 1 to 40 kHz. Results: Null mutant mice had no ABR and no DPOAE responses over the range of stimulation. In contrast, heterozygote and wild-type mice had normal ABR and DPOAE thresholds of 30 to 50 dB in the mid-to-high frequencies. In general, these responses occurred above 6.3 kHz. Conclusion: Both measures of hearing indicate that the COUP-TFI null mutant has profound cochlear dysfunction. Cochlear function in heterozygotes is no different than in wild-type mice. Significance: Even though these mutants have cochleae with many normal anatomic features, these features do not appear to have physiologic relevance. These mutants may be a good model of congenital hearing loss associated with otic capsule malformation. Support: None reported.

The hearing performance with conventional hearing aids and cochlear implants is dramatically reduced in noisy environments and for sounds more complex than speech (e. g. music), partially due to the lack of localized sensorineural activation across different frequency regions with these devices. Laser light can be focused in a controlled manner and may provide more localized activation of the inner ear, the cochlea. We sought to assess whether visible light with parameters that could induce an optoacoustic effect (532 nm, 10-ns pulses) would activate the cochlea. Auditory brainstem responses (ABRs) were recorded preoperatively in anesthetized guinea pigs to confirm normal hearing. After opening the bulla, a 50-microm core-diameter optical fiber was positioned in the round window niche and directed toward the basilar membrane. Optically induced ABRs (OABRs), similar in shape to those of acoustic stimulation, were elicited with single pulses. The OABR peaks increased with energy level (0.6 to 23 microJ/pulse) and remained consistent even after 30 minutes of continuous stimulation at 13 microJ, indicating minimal or no stimulation-induced damage within the cochlea. Our findings demonstrate that visible light can effectively and reliably activate the cochlea without any apparent damage. Further studies are in progress to investigate the frequency-specific nature and mechanism of green light cochlear activation.

The cochlea is the mammalian organ of hearing. Its predominant vibratory element, the basilar membrane, is tonotopically tuned, based on the spatial variation of its mass and stiffness. The constituent collagen fibers of the basilar membrane affect its stiffness. Laser irradiation can induce collagen remodeling and deposition in various tissues. We tested whether similar effects could be induced within the basilar membrane. Trypan blue was perfused into the scala tympani of anesthetized mice to stain the basilar membrane. We then irradiated the cochleas with a 694-nm pulsed ruby laser at 15 or 180 Jcm(2). The mice were sacrificed 14 to 16 days later and collagen organization was studied. Polarization microscopy revealed that laser irradiation increased the birefringence within the basilar membrane in a dose-dependent manner. Electron microscopy demonstrated an increase in the density of collagen fibers and the deposition of new fibrils between collagen fibers after laser irradiation. As an assessment of hearing, auditory brainstem response (ABR) thresholds were found to increase moderately after 15 Jcm(2) and substantially after 180 Jcm(2). Our results demonstrate that collagen remodeling and new collagen deposition occurs within the basilar membrane after laser irradiation in a similar fashion to that found in other tissues.

Visible light is a source of energy known to activate the visual system through absorption by photoreceptors in the eye. When the so-called stress-confinement condition is fulfilled, laser light can induce an acoustic signal through an optoacoustic effect. We sought to assess, if visible light with parameters that induce an optoacoustic effect (i.e., 532nm, 10ns pulses) could be used to stimulate the peripheral hearing organ at ear drum and middle ear level. Auditory brainstem responses (ABRs) were recorded preoperatively in anesthetized guinea pigs to confirm normal hearing. After opening the bulla, a 50-µm core-diameter optical fiber was positioned first in the outer ear canal directed towards the tympanic membrane and then within the bulla directed towards the bony structures within the middle ear as well as towards the round window membrane. Optically-induced ABRs (OABRs), similar in shape to those of acoustic stimulation, were elicited with single pulses after stimulation within the outer as well as the middle ear. The OABR peaks increased with energy level (0.6-23µJ/pulse) but varied in magnitude depending on the location of stimulation. Our findings demonstrate that visible light can be used to activate the peripheral hearing organ when applied at the ear drum level or on bony structures within the middle ear that can transmit vibrations to the cochlea or inner ear. We propose that this novel, non-contact laser stimulation method could be used to improve implantable and non-implantable hearing aids as well as for research purposes.