[Antiseptics in otorhinolaryngology-a substance overview]. / Antiseptika in der HNO-Heilkunde ­ eine Substanzübersicht.

For preoperative skin antisepsis, alcohol-containing iodine solutions and octenidine are suitable. For wound antisepsis, polyhexanide and hypochlorous acid (HOCL) are also available, but only PVP-iodine and HOCL can be applied to cartilage. Chlorhexidine should only be used as mouth- and bodywash for Staphylococcus aureus (MRSA) decolonization. For the many other throat antiseptics, evidence of clinical efficacy is lacking. For decolonization of the nares, polyhexanide and octenidine are available as nasal gels, but these are inferior to mupirocin for MRSA decolonization. PVP-iodine and HOCL are safe to use for nasal irrigation, but only HOCL has proven effective to improve symptoms of chronic rhinosinusitis. All antiseptics exhibit a certain ototoxicity. With an intact eardrum, acetic acid-containing eardrops can be used to prevent and treat external otitis and myringitis. When the eardrum is perforated, only alcohol-free PVP-iodine and HOCL may be used.

Randomized, placebo-controlled study on efficacy, safety and tolerability of drug-induced defibrinogenation for sudden sensorineural hearing loss: the lessons learned.

PURPOSE: Disturbance of cochlear microcirculation is discussed as final common pathway of various inner ear diseases. Hyperfibrinogenemia causing increased plasma viscosity is a possible factor for a critical reduction of cochlear blood flow that might lead to sudden sensorineural hearing loss (SSHL). The aim was to determine the efficacy and safety of drug-induced defibrinogenation by ancrod for SSHL. METHODS: Double-blind, randomized, placebo-controlled, multicenter, parallel group, phase II (proof-of-concept) study (planned enrollment: 99 patients). Patients received an infusion of ancrod or placebo (day 1) followed by subcutaneous administrations (day 2, 4, 6). Primary outcome was the change in pure tone audiogram air conduction average until day 8. RESULTS: The study was terminated early due to slow recruiting (31 enrolled patients: 22 ancrod, 9 placebo). A significant improvement of hearing loss was registered in both groups (ancrod: - 14.3 dB ± 20.4 dB, - 39.9% ± 50.4%; placebo: - 22.3 dB ± 13.7 dB, - 59.1% ± 38.0%). A statistically significant group-difference was not detected (p = 0.374). Placebo response of 33.3% complete and 85.7% at least partial recovery was observed. Plasma fibrinogen levels were reduced significantly by ancrod (baseline: 325.2 mg/dL, day 2: 107.2 mg/dL). Ancrod was tolerated well, no adverse drug reaction was of severe intensity, no serious adverse events occurred. CONCLUSION: Ancrod reduced fibrinogen levels that support its mechanism of action. The safety profile can be rated positively. Since the planned number of patients could not be enrolled, no efficacy conclusion can be drawn. The high rate of placebo response challenges clinical trials for SSHL and needs to be considered in future investigations. Trial registrations This study was registered in the EU Clinical Trials Register, EudraCT-No. 2012-000066-37 at 2012-07-02.

Frequency of bilateral cervical metastases in hypopharyngeal squamous cell carcinoma: a retrospective analysis of 203 cases after bilateral neck dissection.

The decision whether to perform an elective neck dissection in patients with head and neck squamous cell carcinoma and clinically negative lymph nodes (cN0) is made based on the probability of micrometastases in the neck for the given subsite and size of the primary. A retrospective chart review was performed of 203 patients with hypopharyngeal SCC who received a bilateral neck dissection. The frequency of histologically unveiled bilateral neck metastases was determined. A high frequency of contralateral metastases above 20% was detected for all carcinomas affecting the midline and those involving the medial wall of the pyriform sinus except of T1-stages (13%) and a low frequency for laterally located primaries (3%). Ipsilateral nodal status predicted contralateral neck metastases. Bilateral neck dissection should be recommended for primaries affecting the midline and T2-4 tumors involving the medial wall of the pyriform sinus.

Influence of the individual DPOAE growth behavior on DPOAE level variations caused by conductive hearing loss and elevated intracranial pressure.

OBJECTIVES: Minor conductive hearing loss (CHL) can compromise the evaluation of the inner ear function with distortion product otoacoustic emissions (DPOAE). Elevation of the intracranial pressure (ICP) is also expected to alter the middle ear (ME) sound transmission. An impaired ME sound transmission leads to an attenuation of the DPOAE primary tone levels (L1 and L2) during forward transmission and of DPOAE levels (LDP) during backward transmission. The effect of the attenuation of L1 and L2 is complex and might have unexpected effects on DPOAE levels. In this work, CHL- and ICP-induced alterations of LDP versus L1 growth functions (constant L2 and increasing L1) are investigated. The first aim of this study is to explain how alterations of ME sound transmission can affect DPOAEs and to characterize the dependency of DPOAE level alterations on L2,L1 combinations and on the individual shape of LDP versus L1 growth functions. The second aim is to identify analogies between CHL- and ICP-induced alterations of DPOAEs and to discuss implications for a potential noninvasive ICP monitoring. DESIGN: This study focuses on general theoretical considerations, supported by selected experimental observations in different species and simulations. DPOAEs were measured in guinea pigs before and after induction of a CHL (1 ear) and during increased ICP (1 ear), and in humans during changes of the postural position to alter the ICP (4 ears). RESULTS: In both CHL and elevated ICP, DPOAE levels are not only reduced, but LDP versus L1 growth functions exhibit a shift to higher L1. The absolute DPOAE level alterations strongly depend on the L2,L1 combinations and the individual shape of the LDP versus L1 growth functions. In steeper LDP versus L1 growth functions, the DPOAE level alterations exhibit a larger variation. DPOAE levels can even increase. The largest variation can be found in ears with a nonmonotonic DPOAE growth behavior. An example of a guinea pig ear is presented with a nonmonotonic DPOAE growth behavior and a CHL of 4 dB, where the DPOAE level alterations varied between -32 and +9 dB depending on L1. CONCLUSIONS: The data enable a more comprehensive view of DPOAE level alterations during CHL and elevated ICP. The observations also explain the problem that DPOAE and ICP alterations do not correlate linearly. An evaluation of the shift of the LDP versus L1 growth function along the L1 axis provides a potential tool to improve both the assessment of the inner ear function in the presence of a CHL and noninvasive ICP monitoring with DPOAEs.

Simvastatin and Ginkgo biloba in the treatment of subacute tinnitus: a retrospective study of 94 patients.

OBJECTIVES: Studies suggest that hypercholesterolemia promotes the development of inner ear disorders such as tinnitus. However, the underlying pathomechanisms are still not clearly defined. METHODS: A retrospective study was performed to assess whether a reduction of serum cholesterol by 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors may result in a relief of subacute tinnitus. Remission rates of 58 patients were investigated after 4 months of treatment with simvastatin (40 mg). Results were compared to treatment with Ginkgo biloba (120 mg; n = 36) as control group. Differences between tinnitus score at the day of first treatment and after 4 months were used as main outcome measure. RESULTS: After treatment with simvastatin or G biloba, tinnitus score decreased from 41.3 ± 10.4 to 37.4 ± 17.3 and from 44.7 ± 11.2 to 41.2 ± 8.7, respectively. However, independently of the treatment regimen, differences of tinnitus scores were considered not significant. CONCLUSIONS: After administration of simvastatin over 4 months, this retrospective study has shown no significant efficacy in treatment of subacute tinnitus. For a more conclusive answer, further prospective, double-blind, and placebo-controlled studies with a larger number of patients are needed.

Does laryngopharyngeal reflux cause intraoral burning sensations? A preliminary study.

Intraoral burning sensations are a common problem in the otolaryngological practice. The aim of this study was to evaluate if laryngopharyngeal reflux can cause intraoral burning sensations by measuring oropharyngeal acid reflux. Patients with recurring intraoral burning sensations underwent oropharyngeal pH monitoring in our outpatient clinic. The pH catheter was placed at the level of the uvula. The catheter contained an externally worn transmitter, which wirelessly sent the data to a monitor. In addition, patients were instructed to indicate meals or the occurrence of burning sensations by pressing provided buttons on the monitor. Corresponding events of burning sensations and a significant decrease in oropharyngeal pH values should be visualized. Twenty two patients suffering from recurring intraoral burning sensations underwent oropharyngeal pH measurement for 21-25 h. We could find oropharyngeal reflux episodes in 11 patients. However, we could not detect any episodes of burning sensations in the mouth corresponding with a decrease in oropharyngeal pH values. Our results suggest that there is no causal connection between LPR episodes and the occurrence of intraoral burning sensations in the examined patients. Although further studies with more patients are necessary in the future, we conclude from our findings that recurring intraoral burning sensations are not an indication for proton pump inhibitor therapy.

Exhaled and nasal nitric oxide in laryngectomized patients.

BACKGROUND: Nitric oxide (NO) shows differing concentrations in lower and upper airways. Patients after total laryngectomy are the only individuals, in whom a complete separation of upper and lower airways is guaranteed. Thus the objective of our study was to assess exhaled and nasal NO in these patients. METHODS: Exhaled bronchial NO (FENO) and nasal nitric oxide (nNO) were measured in patients after total laryngectomy (n = 14) and healthy controls (n = 24). To assess lung function we additionally performed spirometry. Co-factors possibly influencing NO, such as smoking, infections, and atopy were excluded. RESULTS: There was a markedly (p < 0.001) lower FENO in patients after total laryngectomy (median (range): 4 (1-22) ppb) compared to healthy controls 21 (9-41) ppb). In contrast, nNO was comparable between groups (1368 versus 1380 in controls) but showed higher variability in subjects after laryngectomy. CONCLUSIONS: Our data suggest that either bronchial NO production in patients who underwent laryngectomy is very low, possibly due to alterations of the mucosa or oxidant production/inflammation, or that substantial contributions to FENO arise from the larynx, pharynx and mouth, raising FENO despite velum closure. The data fit to those indicating a substantial contribution to FENO by the mouth in healthy subjects. The broader range of nNO values found in subjects after laryngectomy may indicate chronic alteration or oligo-symptomatic inflammation of nasal mucosa, as frequently found after total laryngectomy.

An animal model for the analysis of cochlear blood flow [corrected] disturbance and hearing threshold in vivo.

Impairment of cochlear blood flow (CBF) is considered to be important in inner ear pathology. However, direct measurement of CBF is difficult and has not been investigated in combination with hearing function. Six guinea pigs were used to show feasibility of an animal model for the analysis of cochlear microcirculation by intravital microscopy in combination with investigation of the hearing threshold by brainstem response audiometry (ABR). By the application of sodium nitroprusside (SNP), CBF was increased over 30 min. Reproducibility of measurements was shown by retest measurements. Mean baseline velocity of CBF was 109 +/- 19 mum/s. Vessel diameters had a mean value of 9.4 +/- 2.7 mum. Mean hearing threshold was 19 +/- 6 dB. In response to SNP, CBF velocity increased significantly to 161 +/- 26 mum/s. Mean arterial pressure decreased significantly to 36 +/- 11 mmHg. After the end of the application, CBF velocity recovered to a minimum of 123 +/- 17 microm/s. Within the retest, CBF velocity significantly increased to a maximum of 160 +/- 31 microm/s. Second recovery of CBF velocity was 125 +/- 14 mum/s. Within the second retest, CBF increased significantly to 157 +/- 25 microm/s. ABR thresholds did not change significantly. The increase in blood flow velocity occurred in spite of substantial hypotension as induced by a vasodilator. This may explain the fact that ABR threshold remained unchanged reflecting a maintained blood supply in this part of the brain. This technique can be used to evaluate effects of treatments aimed at cochlear microcirculation in inner ear pathologies.

Level alterations of the 2f (1)-f (2) distortion product due to hypoxia in the guinea pig depend on the stimulus frequency.

Increased intracranial pressure (ICP) is known to affect the levels of distortion product otoacoustic emissions (DPOAEs) in a frequency-specific manner. DPOAEs might, therefore, be used for monitoring the ICP non-invasively. Hypoxia can also cause alterations of DPOAE levels, which can be distinguished from ICP-related changes only, when their characteristics, in particular frequency specificity, are known in detail. DPOAEs at f (2) = 2, 4, 8, 12 and 16 kHz and oxygen saturation (SaO(2)) were continuously monitored in nine spontaneously breathing guinea pigs, anaesthetized by i.m. administration of midazolam, medetomidin and fentanyl, during the respiration of a gas mixture of N(2)O and O(2) containing either 30% O(2) or 13% O(2). Fourteen hypoxic intervals in eight animals were included into final data analysis. Characteristic hypoxic level alterations with a level decrease and a remarkable level destabilization during hypoxia, and a pronounced reversible level decrease after reoxygenation were observed at the frequencies of 4, 8 and 16 kHz. At 2 and 12 kHz, the only reproducible effect of hypoxia was an increased fluctuation of the DPOAE level, which was significantly less pronounced compared with the other frequencies (P < 0.05 for 12 vs. 16 and 8 kHz and for 2 vs. 16 kHz). DPOAE level alterations due to hypoxia depend on the frequency in guinea pigs. Studies in human are warranted to improve non-invasive ICP monitoring with DPOAE by the detection of hypoxia-related changes.

Quantitative estimation of minor conductive hearing loss with distortion product otoacoustic emissions in the guinea pig.

Subclinical conductive hearing losses (CHLs) can affect otoacoustic emissions and therefore limit their potential in the assessment of the cochlear function. Theoretical considerations to estimate a minor CHL from DPOAE measurements [Kummer et al. (2006). HNO 54, 457-467] are evaluated experimentally. They are based on the fact, that the level difference of the stimulus tones L(1) and L(2) for optimal excitation of the inner ear is given by L(1)=aL(2)+b. A CHL is presumed to attenuate both L(1) and L(2) to the same extent such that excitation of the inner ear is no longer optimal. From the change of L(1) that is necessary to restore optimal excitation of the inner ear and thus to produce maximal DPOAE levels, the CHL can be estimated. In 10 guinea pig ears an experimental CHL was produced, quantified by determination of compound action potential (CAP) thresholds at 8 kHz (CHL(CAP)) and estimated from DPOAE measurements at 8 kHz (CHL(DPOAE)). CHLs up to 12 dB could be assessed. CHL(DPOAE) correlated well with CHL(CAP) (R=0.741, p=0.0142). Mean difference between CHL(DPOAE) and CHL(CAP) was 4.2±2.6 dB. Estimation of minor CHL from DPOAE measurements might help to increase the diagnostic value of DPOAEs.

Calculated parenteral initial treatment of bacterial infections: Infections in the ear, nose, throat and mouth and jaw area.

This is the sixth chapter of the guideline "Calculated initial parenteral treatment of bacterial infections in adults - update 2018" in the 2nd updated version. The German guideline by the Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. (PEG) has been translated to address an international audience. The chapter deals with the antibacterial treatment of more severe infections of the ear, the nose, the throat and the maxillofacial region, including odontogenic and salivary gland infections.

Microbiome and Culture Based Analysis of Chronic Rhinosinusitis Compared to Healthy Sinus Mucosa.

The role of bacteria in chronic rhinosinusitis (CRS) is still not well understood. Whole microbiome analysis adds new aspects to our current understanding that is mainly based on isolated bacteria. It is still unclear how the results of microbiome analysis and the classical culture based approaches interrelate. To address this, middle meatus swabs and tissue samples were obtained during sinus surgery in 5 patients with CRS with nasal polyps (CRSwNP), 5 patients with diffuse CRS without nasal polyps (CRSsNP), 5 patients with unilateral purulent maxillary CRS (upm CRS) and 3 patients with healthy sinus mucosa. Swabs were cultured, and associated bacteria were identified. Additionally, parts of each tissue sample also underwent culture approaches, and in parallel DNA was extracted for 16S rRNA gene amplicon-based microbiome analysis. From tissue samples 4.2 ± 1.2 distinct species per patient were cultured, from swabs 5.4 ± 1.6. The most frequently cultured species from the swabs were Propionibacterium acnes, Staphylococcus epidermidis, Corynebacterium spp. and Staphylococcus aureus. The 16S-RNA gene analysis revealed no clear differentiation of the bacterial community of healthy compared to CRS samples of unilateral purulent maxillary CRS and CRSwNP. However, the bacterial community of CRSsNP differed significantly from the healthy controls. In the CRSsNP samples Flavobacterium, Pseudomonas, Pedobacter, Porphyromonas, Stenotrophomonas, and Brevundimonas were significantly enriched compared to the healthy controls. Species isolated from culture did not generally correspond with the most abundant genera in microbiome analysis. Only Fusobacteria, Parvimonas, and Prevotella found in 2 unilateral purulent maxillary CRS samples by the cultivation dependent approach were also found in the cultivation independent approach in high abundance, suggesting a classic infectious pathogenesis of odontogenic origin in these two specific cases. Alterations of the bacterial community might be a more crucial factor for the development of CRSsNP compared to CRSwNP. Further studies are needed to investigate the relation between bacterial community characteristics and the development of CRSsNP.

Reduction of olfactory sensitivity during normobaric hypoxia.

OBJECTIVE: Acute mountain sickness (AMS) is caused by a low partial pressure of oxygen and may occur above 2500m. The aim of this research was to evaluate olfactory and gustatory abilities of healthy subjects during baseline conditions and after seven hours of normobaric hypoxia. METHODS: Sixteen healthy subjects were assessed using the Sniffin' Sticks, as well as intensity and pleasantness ratings. Gustatory function was evaluated utilizing the Taste Strips. Experiments were carried out under baseline conditions (518m altitude) followed by a second testing session after seven hours of normobaric hypoxia exposure (comparable to 4000m altitude). RESULTS: During normobaric hypoxia olfactory sensitivity and intensity estimates were significantly reduced. CONCLUSIONS: We conclude that normobaric hypoxia leads to a significant decrease of olfactory sensitivity and intensity ratings.

Effect of atorvastatin on progression of sensorineural hearing loss and tinnitus in the elderly: results of a prospective, randomized, double-blind clinical trial.

OBJECTIVE: To test whether the 3-hydroxy-3-methylglutaryl- coenzyme A reductase inhibitor atorvastatin can slow down the progression of presbycusis. PATIENTS: Fifty patients 60- to 75-years-old with presbycusis and moderately elevated serum cholesterol. INTERVENTION(S): In a double-blind design, patients were randomly assigned to treatment with either atorvastatin (40 mg/d orally) or placebo. MAIN OUTCOME MEASURE(S): Pure-tone audiometry and tinnitus evaluation at enrolment and after 7 and 13 months. RESULTS: Development of hearing thresholds after 7 and 13 months showed no significant differences between the groups. Tinnitus score continuously improved in the atorvastatin group (34.8 at 7 and 27.6 at 13 mo), whereas it slightly deteriorated in the placebo group (24.8 at 7 and 26.8 at 13 mo). The effect on tinnitus was a tendency without statistic significance (p = 0.0833). CONCLUSION: Atorvastatin had no effect on the development of hearing thresholds, but resulted in a trend toward a relief of tinnitus.

Labial Salivary Glands in Infants: Histochemical Analysis of Cytoskeletal and Antimicrobial Proteins.

Human labial glands secrete mucous and serous substances for maintaining oral health. The normal microbial flora of the oral cavity is regulated by the acquired and innate immune systems. The localization and distribution of proteins of the innate immune system were investigated in serous acinar cells and the ductal system by the method of immunohistochemistry. Numerous antimicrobial proteins could be detected in the labial glands: ß-defensin-1, -2, -3; lysozyme; lactoferrin; and cathelicidin. Cytoskeletal components such as actin, myosin II, cytokeratins 7 and 19, α- and ß-tubulin were predominantly observed in apical cell regions and may be involved in secretory activities.

Atmospheric Pressure and Onset of Episodes of Menière's Disease - A Repeated Measures Study.

BACKGROUND: External changes of air pressure are transmitted to the middle and inner ear and may be used therapeutically in Menière's disease, one of the most common vertigo disorders. We analyzed the possible relationship of atmospheric pressure and other meteorological parameters with the onset of MD vertigo episodes in order to determine whether atmospheric pressure changes play a role in the occurrence of MD episodes. METHODS: Patients of a tertiary outpatient dizziness clinic diagnosed with MD were asked to keep a daily vertigo diary to document MD episodes (2004-2009). Local air pressure, absolute temperature and dew point temperature were acquired on an hourly basis. Change in meteorological parameters was conceptualized as the maximum difference in a 24 hour time frame preceding each day. Effects were estimated using additive mixed models with a random participant effect. We included lagged air parameters, age, sex, weekday and season in the model. RESULTS: A total of 56 persons (59% female) with mean age 54 years were included. Mean follow-up time was 267 days. Persons experienced on average 10.3 episodes during the observation period (median 8). Age and change in air pressure were significantly associated with vertigo onset risk (Odds Ratio = 0.979 and 1.010). We could not show an effect of sex, weekday, season, air temperature, and dew point temperature. CONCLUSIONS: Change in air pressure was significantly associated with onset of MD episodes, suggesting a potential triggering mechanism in the inner ear. MD patients may possibly use air pressure changes as an early warning system for vertigo attacks in the future.

Susceptibility-weighted angiography visualizes hypoxia in cerebral veins.

OBJECTIVES: The objective of this study was to evaluate the influence of short- and long-term hypoxia on the depiction of cerebral veins in the susceptibility-weighted angiography (SWAN) sequence. MATERIALS AND METHODS: In the context of a study on brain adaptation mechanisms to hypoxia, 16 healthy men (aged 20-28 years) were studied through magnetic resonance imaging (MRI) under room air conditions, short-term-hypoxia (7 minutes before and during the MRI scan), and long-term hypoxia (8.5 hours before and during the MRI scan). Oxygen saturation was continuously measured using a finger-mounted pulse oximeter. Two independent blinded readers compared the 3 scans of each participant and graded the SWAN source images and minimum intensity projections according to the size, number, and signal intensity of the cerebral veins. Signal intensities of deep cerebral veins were measured, and signal intensity proportions of deep cerebral veins to different parenchymal brain regions were calculated. RESULTS: Nine subjects could be included in the study. In all of them, both readers correctly distinguished the 2 hypoxia scans from the baseline scan, grading the SWAN images acquired under hypoxic conditions as visualizing cerebral veins more prominently. Signal intensities of the deep cerebral veins and signal intensity proportions were significantly lower in the hypoxia scans. No significant differences between short-term and long-term hypoxia were found on visual inspections and signal intensity measurements. This correlated with the results of the pulse oximetry: mean O2 saturation values were 97.9% ± 1.2% (baseline), 84.1% ± 3.8% (short-term hypoxia), and 82.8% ± 4.4% (long-term hypoxia), respectively. CONCLUSIONS: Hypoxia leads to visible and measurable changes in cerebral veins as depicted through SWAN. Possible clinical implications of this finding include stroke and tumor imaging and need further investigation.