[Nodal metastasis and value of neck dissection in T1/2 oropharyngeal and hypopharyngeal carcinomas]. / Nodale Metastasierung und Stellenwert der Neck Dissection bei T1/2-Oro- und Hypopharynxkarzinomen.

BACKGROUND: Due to heterogeneous data, the indication for elective neck dissection (END) in patients with squamous cell carcinoma of the hypopharynx and oropharynx (HPSCC and OPSCC) in stages T1/2N0 is somewhat unclear. Therefore, in this multicenter study, we performed detailed analysis of the metastatic behavior of HPSCC and OPSCC. MATERIAL AND METHODS: The nodal metastatic patterns of 262 HPSCC and OPSCC patients who had undergone surgery was retrospectively investigated. In addition, recurrence-free and overall survival were recorded. Furthermore, a systematic literature review on the topic was completed. RESULTS: In patients with HPSCC, a discrepancy between clinical and pathologic N status was recorded in 62.1% of patients vs. 52.4% for p16- OPSCC, and 43.6% for p16+ OPSCC. The occult metastasis rate in cT1/2cN0 primary tumors was 38.9% for HPSCC vs. 17.8% (p16- OPSCC) and 11.1% (p16+ OPSCC). Contralateral metastases occurred in 22.2% of cases for HPSCC at stages cT1/2cN0, compared to only 9.1% for p16- OPSCC, and 0% for p16+ OPSCC patients.Patients with p16+ OPSCC had better recurrence-free and overall survival than p16- OPSCC and HPSCC patients. A direct association between patient survival and the extent of neck surgical therapy could not be demonstrated in our patients. CONCLUSION: Patients with HPSCC are at risk for bilateral neck metastases from stage cT1/2cN0, justifying bilateral END. Patients with T1/2 OPSCC present with occult metastases ipsilaterally in >20% of cases; however, the risk for contralateral occult metastasis is <10%. Hence, in strictly lateralized cT1/2CN0 tumors, omission of contralateral END may be considered.

[Enhanced quality of documentation for biologic therapy of chronic rhinosinusitis through structured digital reporting and indication?] / Qualitätssteigerung der Dokumentation zur Biologikatherapie der chronischen Rhinosinusitis durch digitale, strukturierte Befunderhebung und Indikationsstellung?

BACKGROUND: With targeted inhibition of type 2 inflammation, biologics represent the standard add-on therapy for inadequately controlled severe forms of chronic rhinosinusitis with nasal polyps (CRSwNP). Despite standardization with paper-based checklists, the documentation of medical history and current findings pertinent to indication criteria are a significant challenge for physicians. Through development of an application based on structured reporting, the current study aimed to improve documentation quality and simplify the decision-making process. Previously available paper checklists served as a comparison. METHODS: For this study, a digital incremental tool was programmed to record current findings and check for fulfilment of indication criteria. The tool was compared with other checklists in terms of completeness, time required, and readability. RESULTS: A total of 20 findings were collected for each of the three documentation options and included in the analysis. Documentation with the two paper-based checklists had comparable information content: 17.5 ± 5.1/21.7 ± 7.6 points out of a maximum of 43 points; p > 0.05. Documentation using the digital application led to a significant increase in information content compared to all paper-based documentation. The average score was 38.25 ± 3.7 (88.9% of maximum; p < 0.001). On average, user satisfaction was high (9.6/10). Use of the digital application was initially more time consuming, but as more cases were documented, the time taken improved significantly. CONCLUSION: In the future, structured reporting using apps could replace paper-based reporting for the indication of biologic therapy in CRSwNP patients and offer additional benefits in terms of data quality and traceability of results. The increasing volume of documentation in the future, the progress of digitalization, and the possibility of networking between individual centers make introduction of the app in the near future both likely and economical.

Surprise-minimization as a solution to the structural credit assignment problem.

The structural credit assignment problem arises when the causal structure between actions and subsequent outcomes is hidden from direct observation. To solve this problem and enable goal-directed behavior, an agent has to infer structure and form a representation thereof. In the scope of this study, we investigate a possible solution in the human brain. We recorded behavioral and electrophysiological data from human participants in a novel variant of the bandit task, where multiple actions lead to multiple outcomes. Crucially, the mapping between actions and outcomes was hidden and not instructed to the participants. Human choice behavior revealed clear hallmarks of credit assignment and learning. Moreover, a computational model which formalizes action selection as the competition between multiple representations of the hidden structure was fit to account for participants data. Starting in a state of uncertainty about the correct representation, the central mechanism of this model is the arbitration of action control towards the representation which minimizes surprise about outcomes. Crucially, single-trial latent-variable analysis reveals that the neural patterns clearly support central quantitative predictions of this surprise minimization model. The results suggest that neural activity is not only related to reinforcement learning under correct as well as incorrect task representations but also reflects central mechanisms of credit assignment and behavioral arbitration.

Assessing unknown potential-quality and limitations of different large language models in the field of otorhinolaryngology.

BACKGROUND: Large Language Models (LLMs) might offer a solution for the lack of trained health personnel, particularly in low- and middle-income countries. However, their strengths and weaknesses remain unclear. AIMS/OBJECTIVES: Here we benchmark different LLMs (Bard 2023.07.13, Claude 2, ChatGPT 4) against six consultants in otorhinolaryngology (ORL). MATERIAL AND METHODS: Case-based questions were extracted from literature and German state examinations. Answers from Bard 2023.07.13, Claude 2, ChatGPT 4, and six ORL consultants were rated blindly on a 6-point Likert-scale for medical adequacy, comprehensibility, coherence, and conciseness. Given answers were compared to validated answers and evaluated for hazards. A modified Turing test was performed and character counts were compared. RESULTS: LLMs answers ranked inferior to consultants in all categories. Yet, the difference between consultants and LLMs was marginal, with the clearest disparity in conciseness and the smallest in comprehensibility. Among LLMs Claude 2 was rated best in medical adequacy and conciseness. Consultants' answers matched the validated solution in 93% (228/246), ChatGPT 4 in 85% (35/41), Claude 2 in 78% (32/41), and Bard 2023.07.13 in 59% (24/41). Answers were rated as potentially hazardous in 10% (24/246) for ChatGPT 4, 14% (34/246) for Claude 2, 19% (46/264) for Bard 2023.07.13, and 6% (71/1230) for consultants. CONCLUSIONS AND SIGNIFICANCE: Despite consultants superior performance, LLMs show potential for clinical application in ORL. Future studies should assess their performance on larger scale.

[Results of a survey on the current management of chronic rhinosinusitis with nasal polyps in Germany]. / Ergebnisse einer Umfrage zur aktuellen Behandlung der chronischen Rhinosinusitis mit nasalen Polypen.

INTRODUCTION: With a prevalence of 0.55% to 4%, chronic rhinosinusitis with nasal polyps (CRSwNP) is a relevant part of the daily work of German otolaryngologists. The aim of the questionnaire-based data collection was to assess the current treatment status of CRSwNP in Germany. MATERIAL AND METHODS: For this purpose, 24 questions within an anonymized online questionnaire were sent to all German ENT departments. RESULTS: Of 160 contacted ENT departments, 50 participated in the survey (31.3%). Among these, 76% performed more than 100 sinus surgeries annually and 38% treated more than 50 patients with biologics. Saline irrigations (80%) and intranasal glucocorticoids (GCS, 96%) were the most common conservative therapies. Systemic GCSs (52%) and intranasal GCS irrigation (20%) were less common. 80% of departments used biologics in the therapy of CRSwNP with an overall preference for dupilumab (70%). For therapy of aspirin intolerance, biologics (52%) were preferred to aspirin desensitization (26%). Prior to treatment with biologics clinical workup included the nasal polyp score (90%), the SNOT-22 questionnaire (84%), surrogate markers of type 2 inflammation (60%-72%), and computer tomography (50%). Final treatment success was assessed after 24 weeks (50%). CONCLUSION: Mostly, the responding departments followed German and European recommendations for diagnosis and therapy of CRSwNP. Therapy with biologics is widely used. The value of preoperative systemic GCS and the frequent performance of CT before initiation of therapy with a biologic should be debated in regard to its currently widespread use.

Use of virtual monoenergetic images for reduction of extensive dental implant associated artifacts in photon-counting detector CT.

Aim of this study was to assess the impact of virtual monoenergetic images (VMI) on dental implant artifacts in photon-counting detector computed tomography (PCD-CT) compared to standard reconstructed polychromatic images (PI). 30 scans with extensive (≥ 5 dental implants) dental implant-associated artifacts were retrospectively analyzed. Scans were acquired during clinical routine on a PCD-CT. VMI were reconstructed for 100-190 keV (10 keV steps) and compared to PI. Artifact extent and assessment of adjacent soft tissue were rated using a 5-point Likert grading scale for qualitative assessment. Quantitative assessment was performed using ROIs in most pronounced hypodense and hyperdense artifacts, artifact-impaired soft tissue, artifact-free fat and muscle tissue. A corrected attenuation was calculated as difference between artifact-impaired tissue and tissue without artifacts. Qualitative assessment of soft palate and cheeks improved for all VMI compared to PI (Median PI: 1 (Range: 1-3) and 1 (1-3); e.g. VMI130 keV 2 (1-5); p < 0.0001 and 2 (1-4); p < 0.0001). In quantitative assessment, VMI130 keV showed best results with a corrected attenuation closest to 0 (PI: 30.48 ± 98.16; VMI130 keV: - 0.55 ± 73.38; p = 0.0026). Overall, photon-counting deducted VMI reduce the extent of dental implant-associated artifacts. VMI of 130 keV showed best results and are recommended to support head and neck CT scans.

Exposure-response relationship between work-related hand-arm vibration exposure and musculoskeletal disorders of the upper extremities: the German hand-arm vibration study.

Objective. To quantify the exposure-response relationship between hand-arm vibration exposure and the risk of musculoskeletal disorders of the upper extremities (UMSDs), a case-control study was carried out among workers in the construction, mining, metal and woodworking industries. Methods. In total, 209 male cases and 614 controls were recruited. Cases were newly reported patients with UMSDs. Controls were a random sample of persons with compensable occupational injuries. Standardized personal interviews were performed among cases and controls by well-trained safety engineers. In addition to leisure activities and comorbidities, work histories of all participants were collected in detail. To quantify hand-arm vibration exposures, a database of vibration measurements of over 700 power tools was used. This database allows the detailed quantification of vibration exposures over time. A dose-response relationship between hand-arm vibration exposure and UMSDs was quantified by conditional logistic regression analyses. Results and conclusions. After adjusting for relevant confounders, statistically significant exposure-response relationships between cumulative hand-arm vibration exposure and UMSDs were established. A cumulative hand-arm vibration exposure of Dhv (vibration total value in three measuring directions) = 142,300 (95% confidence interval [CI] [90,600-333,200]) m2/s4·day or Dhw (vibration value in the direction along the forearm) = 38,700 (95% CI [25,400-80,900]) m2/s4·day is associated with a doubled risk of UMSDs.

Structured Reporting of Head and Neck Sonography Achieves Substantial Interrater Reliability.

Purpose Ultrasound examinations are often criticized for having higher examiner dependency compared to other imaging techniques. Compared to free-text reporting, structured reporting (SR) of head and neck sonography (HNS) achieves superior time efficiency as well as report quality. However, there are no findings concerning the influence of SR on the interrater reliability (IRR) of HNS. Materials and Methods Typical pathologies (n=4) in HNS were documented by video/images by two certified head and neck ultrasound instructors. Consequently, structured reports of these videos/images were created by n=9 senior physicians at departments of otolaryngology or maxillofacial surgery with DEGUM instructors on staff. Reports (n=36) were evaluated regarding overall completeness and IRR. Additionally, user satisfaction was assessed by a visual analog scale (VAS). Results SR yielded very high report completeness (91.8%) in all four cases with a substantial IRR (Fleiss' κ 0.73). Interrater agreement was high at 87.2% with very good user satisfaction (VAS 8.6). Conclusion SR has the potential to ensure high-quality examination reports with substantial comparability and very high user satisfaction. Furthermore, big data collection and analysis are facilitated by SR. Therefore, process quality, workflow, and scientific output are potentially enhanced by SR.

Cochlear implantation impairs intracochlear microcirculation and counteracts iNOS induction in guinea pigs.

Introduction: Preservation of residual hearing remains a great challenge during cochlear implantation. Cochlear implant (CI) electrode array insertion induces changes in the microvasculature as well as nitric oxide (NO)-dependent vessel dysfunction which have been identified as possible mediators of residual hearing loss after cochlear implantation. Methods: A total of 24 guinea pigs were randomized to receive either a CI (n = 12) or a sham procedure (sham) by performing a cochleostomy without electrode array insertion (n = 12). The hearing threshold was determined using frequency-specific compound action potentials. To gain visual access to the stria vascularis, a microscopic window was created in the osseous cochlear lateral wall. Cochlear blood flow (CBF) and cochlear microvascular permeability (CMP) were evaluated immediately after treatment, as well as after 1 and 2 h, respectively. Finally, cochleae were resected for subsequent immunohistochemical analysis of the iNOS expression. Results: The sham control group showed no change in mean CBF after 1 h (104.2 ± 0.7%) and 2 h (100.8 ± 3.6%) compared to baseline. In contrast, cochlear implantation resulted in a significant continuous decrease in CBF after 1 h (78.8 ± 8.1%, p < 0.001) and 2 h (60.6 ± 11.3%, p < 0.001). Additionally, the CI group exhibited a significantly increased CMP (+44.9% compared to baseline, p < 0.0001) and a significant increase in median hearing threshold (20.4 vs. 2.5 dB SPL, p = 0.0009) compared to sham after 2 h. Intriguingly, the CI group showed significantly lower iNOS-expression levels in the organ of Corti (329.5 vs. 54.33 AU, p = 0.0003), stria vascularis (596.7 vs. 48.51 AU, p < 0.0001), interdental cells (564.0 vs. 109.1 AU, p = 0.0003) and limbus fibrocytes (119.4 vs. 18.69 AU, p = 0.0286). Conclusion: Mechanical and NO-dependent microvascular dysfunction seem to play a pivotal role in residual hearing loss after CI electrode array insertion. This may be facilitated by the implantation associated decrease in iNOS expression. Therefore, stabilization of cochlear microcirculation could be a therapeutic strategy to preserve residual hearing.

Impact of Bariatric Surgery on the Stability of the Genetic Material, Oxidation, and Repair of DNA and Telomere Lengths.

Obesity causes genetic instability, which plays a key-role in the etiology of cancer and aging. We investigated the impact of bariatric surgery (BS) on DNA repair, oxidative DNA damage, telomere lengths, alterations of antioxidant enzymes and, selected proteins which reflect inflammation. The study was realized with BS patients (n = 35). DNA damage, base oxidation, BER, and NER were measured before and 1 month and 6 months after surgery with the single-cell gel electrophoresis technique. SOD and GPx were quantified spectrophotometrically, malondealdehyde (MDA) was quantified by HPLC. Telomere lengths were determined with qPCR, and plasma proteome profiling was performed with high-resolution mass spectrophotometry. Six months after the operations, reduction of body weight by 27.5% was observed. DNA damage decreased after this period, this effect was paralleled by reduced formation of oxidized DNA bases, a decline in the MDA levels and of BER and NER, and an increase in the telomere lengths. The activities of antioxidant enzymes were not altered. Clear downregulation of certain proteins (CRP, SAA1) which reflect inflammation and cancer risks was observed. Our findings show that BS causes reduced oxidative damage of DNA bases, possibly as a consequence of reduction of inflammation and lipid peroxidation, and indicate that the surgery has beneficial long-term health effects.

Development and Integration of DOPS as Formative Tests in Head and Neck Ultrasound Education: Proof of Concept Study for Exploration of Perceptions.

In Germany, progress assessments in head and neck ultrasonography training have been carried out mainly theoretically and lack standardisation. Thus, quality assurance and comparisons between certified courses from various course providers are difficult. This study aimed to develop and integrate a direct observation of procedural skills (DOPS) in head and neck ultrasound education and explore the perceptions of both participants and examiners. Five DOPS tests oriented towards assessing basic skills were developed for certified head and neck ultrasound courses on national standards. DOPS tests were completed by 76 participants from basic and advanced ultrasound courses (n = 168 documented DOPS tests) and evaluated using a 7-point Likert scale. Ten examiners performed and evaluated the DOPS after detailed training. The variables of "general aspects" (6.0 Scale Points (SP) vs. 5.9 SP; p = 0.71), "test atmosphere" (6.3 SP vs. 6.4 SP; p = 0.92), and "test task setting" (6.2 SP vs. 5.9 SP; p = 0.12) were positively evaluated by all participants and examiners. There were no significant differences between a basic and advanced course in relation to the overall results of DOPS tests (p = 0.81). Regardless of the courses, there were significant differences in the total number of points achieved between individual DOPS tests. DOPS tests are accepted by participants and examiners as an assessment tool in head and neck ultrasound education. In view of the trend toward "competence-based" teaching, this type of test format should be applied and validated in the future.

The German hearing in noise test with a female talker: development and comparison with German male speech test.

PURPOSE: The aim of the study was to develop the German Hearing in Noise Test (HINT) with female speaker by fulfilling the recommendations by International Collegium of Rehabilitative Audiology (ICRA) for using a female speaker to create new multilingual speech tests and to determine norms and to compare these norms with German male speech tests-the male speakers HINT and the Oldenburg Sentence Test (OLSA). METHODS: The HINT with a female speaker consists of the same speech material as the male speaking HINT. After recording the speech material, 10 normal hearing subjects were included to determine the performance-intensity function (PI function). 24 subjects were part of the measurements to determine the norms and compare them with the norms of male HINT and OLSA. Comparably, adaptive, open-set methods under headphones (HINT) and sound field (OLSA) were used. RESULTS: Acoustic phonetic analysis demonstrated significant difference in mean fundamental frequency, its range and mean speaking rate between both HINT speakers. The calculated norms by three of the tested four conditions of the HINT with a female speaker are not significantly different from the norms with a male speaker. No significant effect of the speaker's gender of the first HINT measurement and no significant correlation between the threshold results of the HINT and the OLSA were determined. CONCLUSIONS: The Norms for German HINT with a female speaker are comparable to the norms of the HINT with a male speaker. The speech intelligibility score of the HINT does not depend on the speakers' gender despite significant difference of acoustic-phonetic parameters between the female and male HINT speaker's voice. Instead, the speech intelligibility rating must be seen as a function of the used speech material.

Hearing rehabilitation for unilateral deafness using a cochlear implant: the influence of the subjective duration of deafness on speech intelligibility.

BACKGROUND: For patients with single sided deafness (SSD) or severe asymmetric sensorineural hearing loss (ASHL), cochlear implantation remains the only solution to restore bilateral hearing capacity. Prognostically, the duration of hearing loss in terms of audiological outcome is not yet clear. Therefore, the aim of this study was to retrospectively investigate the influence of subjective deafness duration on postoperative speech perception after cochlear implantation for SSD as well as its impact on quality of life. MATERIALS AND METHODS: The present study included a total of 36 adults aged 50.2 ± 15.5 years who underwent CI for SSD/ASHL at our clinic between 2010 and 2015. Patients were audiometrically assessed at 3 and 12-36 months postoperatively. Test results were correlated with self-reported duration of deafness. Quality of life was assessed by questionnaire. RESULTS: Mean duration of deafness was 193.9 ± 185.7 months. The side-separated hearing threshold showed an averaged target range between 30 and 40 dB HL. Freiburg monosyllable test increased from 0% pre-operatively to 20% after 3 months (p = 0.001) and to 50% after 12-36 months (p = 0.002). There was a significant correlation between audiometric outcome and subjective deafness duration at 12-36 months postoperatively (r = - 0.564; p = 0.02) with a cutoff for open-set monosyllable recognition at a duration of deafness of greater than 408 months. Quality of life was significantly improved by CI. CONCLUSIONS: CI implantation in unilaterally deafened patients provides objective and subjective benefits. Duration of deafness is unlikely to be an independent negative predictive factor and thus should not generally be considered as contraindication.

Acute physiological and functional effects of repetitive shocks on the hand-arm system: a pilot study on healthy subjects.

Objectives. Exposure to hand-transmitted shocks is a widespread phenomenon in the workplace. Separate risk assessments for shocks do not exist in current international hand-arm vibration regulations, leading to potential underestimation of associated health risks. Methods. In a pilot study approach, eight healthy males were exposed to sets of 3 × 5 min of repetitive shocks and 1 × 5 min of random vibration, controlled at a weighted vibration total value of 10 m/s2. Baseline and post-exposure measurements of vibration perception thresholds, finger skin temperature, maximal grip/pinch force and the Purdue pegboard test were conducted. Muscle activity was monitored continuously by surface electromyography. Results. Shock exposures evoked a temporary increase of vibration perception thresholds with high examination frequencies. A decrease of skin temperature was hinted for shocks of 1 and 20 s-1. Electromyographical findings indicated an additional load on two forearm muscles during shock transmission. Maximum grip force and manual dexterity were not affected, and pinch force only partially reduced after the exposures. Conclusion. Physiological effects from shock exposure conform to those described for hand-arm vibration exposure in principle, although some divergence can be hypothesized. Randomized designs are required to conclusively assess the need of occupational health concepts specifically for hand-transmitted shocks.

Task Learnability Modulates Surprise but Not Valence Processing for Reinforcement Learning in Probabilistic Choice Tasks.

The goal of temporal difference (TD) reinforcement learning is to maximize outcomes and improve future decision-making. It does so by utilizing a prediction error (PE), which quantifies the difference between the expected and the obtained outcome. In gambling tasks, however, decision-making cannot be improved because of the lack of learnability. On the basis of the idea that TD utilizes two independent bits of information from the PE (valence and surprise), we asked which of these aspects is affected when a task is not learnable. We contrasted behavioral data and ERPs in a learning variant and a gambling variant of a simple two-armed bandit task, in which outcome sequences were matched across tasks. Participants were explicitly informed that feedback could be used to improve performance in the learning task but not in the gambling task, and we predicted a corresponding modulation of the aspects of the PE. We used a model-based analysis of ERP data to extract the neural footprints of the valence and surprise information in the two tasks. Our results revealed that task learnability modulates reinforcement learning via the suppression of surprise processing but leaves the processing of valence unaffected. On the basis of our model and the data, we propose that task learnability can selectively suppress TD learning as well as alter behavioral adaptation based on a flexible cost-benefit arbitration.

Investigations concerning the impact of consumption of hot beverages on acute cytotoxic and genotoxic effects in oral mucosa cells.

Consumption of very hot beverages and foods increases the incidence of oral and esophageal cancer but the mechanisms are not known and the critical temperature is not well defined. We realized a study with exfoliated cells from the oral cavity of individuals (n = 73) that live in an area in Iran which has the highest incidence of EC worldwide. Consumption of beverages at very high temperatures is a characteristic feature of this population. We analyzed biomarkers which are (i) indicative for genetic instability (micronuclei that are formed as a consequence of chromosomal damage, nuclear buds which are a consequence of gene amplifications and binucleated cells which reflect mitotic disturbances), (ii) markers that reflect cytotoxic effects (condensed chromatin, karyorrhectic, karyolitic and pyknotic cells), (iii) furthermore, we determined the number of basal cells which is indicative for the regenerative capacity of the buccal mucosa. The impact of the drinking temperature on the frequencies of these parameters was monitored with thermometers. We found no evidence for induction of genetic damage but an increase of the cytotoxic effects with the temperature was evident. This effect was paralleled by an increase of the cell division rate of the mucosa which was observed when the temperature exceeded 60 °C. Our findings indicate that cancer in the upper digestive tract in drinkers of very hot beverages is not caused by damage of the genetic material but by an increase of the cell division rate as a consequence of cytotoxic effects which take place at temperatures over 60 °C. It is known from earlier experiments with rodents that increased cell divisions lead to tumor promotion in the esophagus. Our findings provide a mechanistic explanation and indicate that increased cancer risks can be expected when the drinking temperature of beverages exceeds 60 °C.

In vivo analysis of noise dependent activation of white blood cells and microvascular dysfunction in mice.

This article contains supporting information on data collection for the research article entitled "Aircraft noise exposure drives the activation of white blood cells and induces microvascular dysfunction in mice" by Eckrich et al. We found that noise-induced stress triggered microvascular dysfunction via involvement of innate immune-derived reactive oxygen species. In this article, we present the instrumentation of mice with dorsal skinfold chambers for in vivo microscopic imaging of blood flow, interaction of leukocytes with the vascular wall (also by fluorescent labelling of blood cells) and vessel diameter. In addition, we explain the preparation of cerebral arterioles for measurement of vascular reactivity in vitro.•visualization of noise-dependent effects in dorsal skinfold chamber.•in vivo microscopy of noise-dependent activation of white blood cells.•analysis of noise-dependent microvascular dysfunction in dorsal skinfold chamber and cannulated cerebral arterioles.

Regulation of Endothelial Nitric Oxide Synthase in the Reticular Lamina of the Organ of Corti by a Nitric Oxide Donor.

In the vertebrate cochlea, the reticular lamina seals the organ of Corti against the endolymph filled scala media. After noise exposure, fast alterations in the endothelial nitric oxide synthase (eNOS) expression level were identified in this cochlear structure. Minor amounts of nitric oxide (NO) produced by eNOS or applied by NO donors such as S-nitroso-N-acetyl-penicillamine (SNAP) might protect this vulnerable part of the organ of Corti, on the line of gap junctions of supporting cells and cochlear microcirculation. In n=5 anesthetized guinea pigs, SNAP was intravenously applied in two concentrations. Six untreated animals served as controls. The cochleae were removed and prepared for immunoelectron microscopy using specific gold-labeled anti-eNOS antibodies. The density of the gold particles was quantified for seven cellular regions in the reticular lamina at the ultrastructural level. Following SNAP application, a significant increase in eNOS expression (+176%) was detected compared with controls (p=0.012). The increase occurred mainly in actin-rich cuticular structures and the prominent microtubules bundles. Correlation analysis revealed three clear and five moderate cellular associations for controls, whereas only one clear and one moderate after SNAP application. Thus, application of the NO donor SNAP resulted in an increase in eNOS expression in distinct regions of the reticular lamina.