Klinik und Poliklinik für Hals-, Nasen-, Ohrenheilkunde

Combined electric and acoustic stimulation (EAS) of the auditory system is a new therapy for patients with severe to profound high- and mid-frequency hearing loss but remaining low-frequency hearing. In a prospective study, 13 patients with low-frequency hearing of better than 60 dB below 1 kHz were implanted with a MED-EL COMBI 40+ cochlear implant. Pure tone thresholds as well as monosyllabic word scores and Hochmair-Schulz-Moser sentences in quiet and in noise were measured with hearing aids, cochlear implant alone and in the combined stimulation mode (EAS) in the same ear. Hearing could be partially preserved in 11 out of the 13 patients. All patients scored significantly higher with cochlear implant alone than with hearing aids. Seven patients scored higher in the EAS mode than with cochlear implant alone for sentences in noise, 4 remained unchanged, and 2 could not use EAS. Synergistic effects of EAS were most prominent for hearing in noise with increases of up to 72% as compared to cochlear implant alone.

BACKGROUND AND PURPOSE: Our aim was to determine the value of echo-planar diffusion-weighted MR imaging (epiDWI) in differentiating various types of primary parotid gland tumors. MATERIALS AND METHODS: One hundred forty-nine consecutive patients with suspected tumors of the parotid gland were examined with an epiDWI sequence by using a 1.5T unit. Image analysis was performed by 2 radiologists independently, and the intraclass correlation coefficient was computed. Histologic diagnosis was obtained in every patient. For comparison of apparent diffusion coefficients (ADCs), a paired 2-tailed Student t test with a Bonferroni correction was used. RESULTS: In 136 patients, a primary parotid gland tumor was confirmed by histology. Among the observers, a high correlation was calculated (0.98). ADC values of pleomorphic adenomas were significantly higher than those of all other entities, except for myoepithelial adenomas (P = .054). ADC values of Warthin tumors were different from those of myoepithelial adenomas, lipomas, and salivary duct carcinomas (P < .001, 0.013, and .037, respectively). Mucoepidermoid carcinomas, acinic cell carcinomas, and basal cell adenocarcinomas were not differentiable from Warthin tumors (P = .094, .396, and .604, respectively). CONCLUSION: epiDWI has the potential to differentiate pleomorphic adenoma and myoepithelial adenomas from all other examined entities. Due to an overlap not only within the group of benign and malignant lesions but also between groups, diagnoses should not be addressed on the basis of ADC values solely. Therefore, further studies combining DWI, morphologic criteria, and probably other MR imaging techniques seem warranted.

CONCLUSION: The comprehensive Hearing Preservation classification system presented in this paper is suitable for use for all cochlear implant users with measurable pre-operative residual hearing. If adopted as a universal reporting standard, as it was designed to be, it should prove highly beneficial by enabling future studies to quickly and easily compare the results of previous studies and meta-analyze their data. OBJECTIVES: To develop a comprehensive Hearing Preservation classification system suitable for use for all cochlear implant users with measurable pre-operative residual hearing. METHODS: The HEARRING group discussed and reviewed a number of different propositions of a HP classification systems and reviewed critical appraisals to develop a qualitative system in accordance with the prerequisites. RESULTS: The Hearing Preservation Classification System proposed herein fulfills the following necessary criteria: 1) classification is independent from users' initial hearing, 2) it is appropriate for all cochlear implant users with measurable pre-operative residual hearing, 3) it covers the whole range of pure tone average from 0 to 120 dB; 4) it is easy to use and easy to understand.

BACKGROUND: According to the World Health Organization (WHO), by 2025 there will be approximately 1.2 billion people in the world over the age of 60, which marks a shift in world population to a greater proportion of older people. An estimated 70-80% of adults between 65 and 75 years of age suffer from presbycusis, or age-related, bilateral sensorineural hearing loss (HL) in the high frequencies. Presbycusis is correlated with decreased quality of life (QoL) and depression and according to WHO, is a leading cause of years lived with disability in the adult years. OBJECTIVE: The purpose of the current study was to review the body of literature on treatment options and considerations for the elderly population, as there is a variety of audio-technology available today to treat presbycusis. METHODS: A PubMed literature search was conducted using the keywords 'presbycusis/presbyacusis/geriatric AND hearing aids/cochlear implants/electric acoustic stimulation/middle ear implants' and 'elderly AND cochlear implants'. References were also mined from papers found. RESULTS: 431 articles were considered in this review of treatment options for elderly patients suffering from presbycusis. CONCLUSION: Hearing aids and cochlear implants (CIs) are the most commonly used devices for treating mild-severe presbycusis. Reported outcomes with hearing aids indicate they are an effective method for treating mild-moderate HL in cases where the patient is appropriately fitted and is willing, motivated, and able to use the device. Depending on the type and severity of the HL and the specific needs of the patient, electric-acoustic stimulation and active middle ear implants may also be appropriate solutions for treating presbycusis. Finally, very positive QoL and speech perception outcomes have been documented in treating severe-profound presbycusis with CIs. In some studies, QoL outcomes have even exceeded expectations of elderly patients.

UNLABELLED: SAFETY and efficacy of sublingual (sublingual-swallow) immunotherapy (IT) with house dust mite extract were evaluated in 30 children (6-15 2/3 years of age) over the first 12 months of an ongoing study. The cumulative dose was 570 micrograms Der p I (five times that administered with subcutaneous therapy). SAFETY: One patient on active treatment dropped out after 8 weeks because of a subjective feeling of severe weakness, questionably induced by the therapy. Five patients on active therapy and one patient on placebo reported minor local side effects. EFFICACY: Pulmonary symptoms were reduced after 12 months in actively treated asthmatics, but this was not consistent with the lack of improvement in bronchial reactivity, skin sensitivity and specific IgG and IgG4 against D.pt. in this group. In patients with rhinitis nasal sensitivity was reduced in the placebo group without concomitant improvement in the nasal symptom score. Specific IgE (D.pt. and D.f.) increased significantly more in the active treatment group after 3 and 12 months. We conclude that sublingual IT over 12 months with the fivefold Der p 1 dose of subcutaneous IT was well tolerated, but there was no consistent clinical or immunological benefit compared to placebo.

BACKGROUND: According to the World Health Organization, hearing loss is one of the six leading contributors to the global burden of disease. It is becoming an ever more important problem in society at large, not just because the population is aging, but also because young people increasingly spend their leisure time in activities that expose them to excessive noise. On the other hand, the treatment of hearing loss is improving, as the result of technical developments in otological surgery, hearing aids, and cochlear implants. For nearly every type of hearing loss, there is now some type of rehabilitative treatment. The prerequisite to effective care is timely and accurate diagnosis. METHOD: Review of the pertinent literature and national guidelines. RESULTS AND CONCLUSION: The available epidemiological data on hearing loss in Germany are inadequate. It is roughly estimated that 13 to 14 million people in Germany are in need of treatment for hearing loss. The most common types of permanent hearing loss are those associated with old age, chronic otitis media, and acoustic trauma. Transient hearing loss is particularly common in childhood as a result of inadequate ventilation of the middle ear. The further technical development of cochlear implants has now widened their indications to include severe congenital deafness and presbycusis.

A high intracellular chloride concentration in immature neurons leads to a depolarizing action of GABA that is thought to shape the developing neuronal network. We show that GABA-triggered depolarization and Ca2+ transients were attenuated in mice deficient for the Na-K-2Cl cotransporter NKCC1. Correlated Ca2+ transients and giant depolarizing potentials (GDPs) were drastically reduced and the maturation of the glutamatergic and GABAergic transmission in CA1 delayed. Brain morphology, synaptic density, and expression levels of certain developmental marker genes were unchanged. The expression of lynx1, a protein known to dampen network activity, was decreased. In mice deficient for the neuronal Cl(-)/HCO(3)(-) exchanger AE3, GDPs were also diminished. These data show that NKCC1-mediated Cl(-) accumulation contributes to GABAergic excitation and network activity during early postnatal development and thus facilitates the maturation of excitatory and inhibitory synapses.

Duplications of the distal long arm of the X chromosome are rare and carrier females are usually phenotypically normal. We report on a 14-year-old short statured (height and weight <3rd centile) girl with dup(X)(q26.2q27.1) inherited from a short mother. The proband has minor dysmorphic features, lordosis, lack of menarche, late signs of puberty, low prepuberal levels of gonadotrophins and steroids, but borderline low IGF-1 and normal IGF-Bp3 serum levels. Both the proposita and her mother have severe speech problems with stuttering and dyslalia. The 44-year-old mother with a strikingly aged face and a prominent nose, had menarche at 15 years. Both maternal sisters and the grandmother of the proposita are also short. Karyotyping revealed an additional band at Xq26 in all metaphases from the proband, her mother, and two maternal aunts. Molecular cytogenetic investigations revealed an Xq26.2-q27.1 direct duplication of approximately 7.5 Mb that encompasses or disrupts the SOX3 gene, which maps at the distal border of the duplicated segment. A similar chromosomal duplication was reported recently in five families and in each was associated with an abnormal phenotype in males with short stature [Hol et al., 2000; Solomon et al., 2002, 2004]. Using an androgen-receptor (HUMARA) gene methylation assay and FISH, we show that despite preferential inactivation of the dup(Xq) chromosome a significant proportion of lymphocytes in both mother and daughter carry an active duplicated X chromosome. Our findings further suggest that a dosage effect of SOX3 may to be responsible for a speech disorder in addition to short stature secondary to hypopituitarism.

RATIONALE: Endothelial dysfunction and atherosclerosis are chronic inflammatory diseases characterized by activation of the innate and acquired immune system. Specialized protein receptors of the innate immune system recognize products of microorganisms and endogenous ligands such as nucleic acids. Toll-like receptor 3 (TLR3), for example, detects long double-stranded RNA and is abundantly expressed in endothelial cells. Whether innate immunity contributes to atherogenic mechanisms in endothelial cells is poorly understood. OBJECTIVE: We sought to determine the effects of TLR3 activation in endothelial cells. METHODS AND RESULTS: We first investigated whether stimulation of TLR3 influences endothelial biology in mice. Intravenous injection of polyinosine polycytidylic acid, a synthetic double-stranded RNA analog and TLR3 ligand, impaired endothelium-dependent vasodilation, increased vascular production of reactive oxygen species, and reduced reendothelialization after carotid artery injury in wild-type mice compared with controls but had no effect in TLR3(-/-) animals. TLR3 stimulation not only induced endothelial dysfunction but also enhanced the formation of atherosclerotic plaques in apolipoprotein E-deficient mice. In vitro incubation of endothelial cells with polyinosine polycytidylic acid induced production of the proinflammatory cytokines interleukin-8 and interferon-γ-induced protein 10, increased formation of reactive oxygen species, diminished proliferation, and increased apoptosis, which suggests that endothelial cells are able to directly detect and respond to TLR3 ligands. Neutralization of interleukin-8 and interferon-γ-induced protein 10 antagonizes the observed negative effects of polyinosine polycytidylic acid. We found elevated levels of circulating endothelial progenitor cells in polyinosine polycytidylic acid-treated mice, although they displayed increased endothelial dysfunction. Stimulation of TLR3 in cultured endothelial progenitor cells, however, led to increased formation of reactive oxygen species, increased apoptosis, and reduced migration. Injection of endothelial progenitor cells that had been incubated with polyinosine polycytidylic acid ex vivo hindered reendothelialization after carotid artery injury. Therefore, endothelial progenitor cell function was affected by TLR3 stimulation. Finally, apolipoprotein E-deficient/TLR3-deficient mice exhibited improved endothelial function compared with apolipoprotein E-deficient/TLR3(+/+) littermates. CONCLUSIONS: Immunorecognition of long double-stranded RNA by endothelial cells may be an important mechanism involved in endothelial cell activation and development of endothelial dysfunction.

The pharmacokinetics of gentamicin, tobramycin, and amikacin in inner ear fluids, serum, cerebrospinal fluid, and the compartments of the eye were studied and compared in guinea pigs. The concentrations of antibiotic were determined by microbiologic methods and were confirmed by the use of 14C-labeled gentamicin. Retention was clearly demonstrated in perilymph, in which the half-lives of gentamicin, tobramycin, and amikacin were 12, 11, and 10 hr, respectively. The concentrations of drug in perilymph were symmetrical and were many times higher than the concentrations of antibiotic in the brain. There was no difference between the concentration of drug in endolymph and that in perilymph. A linear relation between concentrations in the perilymph and the dosage of gentamicin was ascertained. Long-term treatment did not influence the pharmacokinetics of the three antibiotics in the inner ear. However, increased levels of drug in the inner ear in animals with uremia and in some animals with otitis media explained the increased ototoxicity that occurs in treatment of these two conditions. Suboccipital puncture and diuresis did not change the concentrations of aminoglycoside antibiotics in the inner ear. Antibiotics applied locally in the middle ear had high degrees of ototoxicity.

Zusammenfassung Die Übersichtarbeit fasst die aktuellen Erkenntnisse der Auswirkung der COVID-19-Pandemie für die Arbeit der HNO-Ärztin und des HNO-Arztes zusammen. Die aktuell diskutierte Rolle einer Anosmie oder Hyposmie als COVID-19-assoziiertes Symptom wird dargestellt. Wir diskutieren das klinische Management aller HNO-Fälle, aber insbesondere von COVID-19-erkrankten Patienten aus Sicht der HNO-Heilkunde. Ein besonderes Augenmerk gilt den Auswirkungen auf die HNO-Untersuchung und auf HNO-ärztliche Operationen.

Die Insomnie, d. h. eine Ein- und/oder Durchschlafstörung, die sich negativ auf die Leistungsfähigkeit und Tagesbefindlichkeit auswirkt, ist eine der häufigsten Erkrankungen in der Allgemeinbevölkerung. Sie wird derzeit meistens pharmakologisch und/oder psychotherapeutisch behandelt, wobei die pharmakologische Behandlung mit Benzodiazepin-Rezeptor-Agonisten zu Abhängigkeit führen kann und die Verfügbarkeit von für die Insomnie-Therapie ausgebildeten Psychotherapeuten momentan nicht in ausreichendem Maße gegeben ist. Durch innovative Behandlungsmethoden könnte hier eine Versorgungslücke effektiv geschlossen werden. Hierzu zählt die auditorische Stimulation, welche vorhandene Sinneskanäle nutzt, um den Schlaf zu beeinflussen. Bisher wurde die auditorische Stimulation vor allem zur Untersuchung von Prozessen der Gedächtniskonsolidierung bei gesunden Probanden angewendet, wobei erfolgreich eine Erhöhung langsamer Oszillationen erreicht wurde, welche vor allem während des Tiefschlafs auftreten. Erste Befunde und sekundäre Outcome-Parameter liefern Hinweise, dass die Potenzierung langsamer Oszillationen durch auditorische Stimulation den Schlaf vertiefen kann, jedoch wurde hierzu bislang keine Studie mit Insomniepatienten durchgeführt. Weitere Forschung bezüglich des Einflusses der Potenzierung langsamer Oszillationen auf die Linderung von Ein- und Durchschlafproblemen bei vorliegender nichtorganischer Insomnie erscheint daher geboten zu sein, um der hohen Beschwerdelast dieser Patientengruppe entgegenzuwirken.

Computer assisted surgery (CAS) is a new imaging technique designed to assist the head and neck surgeon during surgery. This method is based upon a three-dimensional volume model of the patient's skull generated by computer tomographic imaging procedures such as CT and MR. Body points can be marked in the 3-D model by intra-operative correlation of model and patient using a volume digitizer. Real-time positioning of surgical instruments without visual control can be achieved. The use of the system in surgery of the skull base, orbit and the paranasal sinuses is demonstrated.

Die faszinierenden Möglichkeiten, die eine Cochlea-Implantat-Versorgung für taub geborene oder ertaubte Kinder und Erwachsene bietet, haben in den letzten zwei Jahrzehnten ein interdisziplinäres Forschungsfeld entstehen lassen, das sich rasant entwickelt hat.

High attrition rates of novel anti-cancer drugs highlight the need for improved models to predict toxicity. Although polo-like kinase 1 (Plk1) inhibitors are attractive candidates for drug development, the role of Plk1 in primary cells remains widely unexplored. Therefore, we evaluated the utility of an RNA interference-based model to assess responses to an inducible knockdown (iKD) of Plk1 in adult mice. Here we show that Plk1 silencing can be achieved in several organs, although adverse events are rare. We compared responses in Plk1-iKD mice with those in primary cells kept under controlled culture conditions. In contrast to the addiction of many cancer cell lines to the non-oncogene Plk1, the primary cells' proliferation, spindle assembly and apoptosis exhibit only a low dependency on Plk1. Responses to Plk1-depletion, both in cultured primary cells and in our iKD-mouse model, correspond well and thus provide the basis for using validated iKD mice in predicting responses to therapeutic interventions. Polo-like kinase 1 is a key regulator of mitosis and is a candidate for drug development to treat cancer. Here, reduced expression of polo-like kinase 1 in adult mice has a minor impact on animal physiology, suggesting that polo-like kinase 1 inhibitors may be useful in the killing of tumour cells while sparing normal cells.

Abstract Hypoglossal–facial anastomosis (HFA), used in humans for the treatment of facial palsy, was experimentally performed in adult female Wistar rats. The time course of facial reinnervation and the extent of the new motor nerve supply of the vibrissal muscles that develops after HFA were estimated by counting all motoneurons in the brainstem labeled by injection of horseradish peroxidase (HRP) into the whisker pad; muscle innervation by motor endplates was not studied. In untreated animals, HRP injection labels 1,254 ± 54 (mean ± S.D.; n = 6) motoneurons, localized exclusively in the lateral subdivision of the facial nucleus. Immediately following HFA, this number drops to zero. The first HRP‐labeled motoneurons appear in the hypoglossal nucleus at 28 days postoperation (dpo) and at 56 dpo their number reaches 1,096 ± 48. Unexpectedly, the facial nerve, whose proximal stump has been left as blind end during surgery, additionally sends axons to the facial periphery. This resprouting is first detected at 42 dpo with HRP‐marked neurons throughout the facial nucleus lacking somatotopic organiza‐tion. The number of these labeled neurons also rises with time, and at 56 dpo, a total of 1,797 ± 142 facial and hypoglossal motoneurons, that is, 43% more motoneurons than in normal animals, supplies the whisker pad. This hyperinnervation, that is, the projection of more moto‐neurons into the target muscle than under normal conditions‐further increases to 1,978 ± 92 motoneurons at 224 dpo and may provide a new animal model for studying the competitive relationships between motoneurons in their search for peripheral targets. © 1993 Wiley‐Liss, Inc.

Innate and antigen-specific antiviral immunity are triggered by immunorecognition of viral nucleic acids. The helicase retinoic acid-inducible gene I (RIG-I) (also known as DDX58) is the key sensor of negative strand RNA viruses in the cytosol of cells. RNA containing a triphosphate at the 5'-end was shown to activate RIG-I, but the exact structure of RNA supporting 5'-triphosphate recognition, the requirement of a 5'-triphosphate group, as well as the existence of RNA structures detected by RIG-I in the absence of 5'-triphosphate remain controversial. Here, we revisit the literature on RIG-I and RIG-I ligands. The literature proposes at least six different RIG-I ligands: (i) single strand with a 5'-triphosphate, (ii) double-stranded RNA with a 5'-triphosphate, (iii) 5'-triphosphate single-stranded RNA with A- and U-rich 3'-sequences, (iv) double-stranded RNA of intermediate length (>300 and <2000 bp) without 5'-triphosphate, (v) blunt-end short double-stranded RNA (23-30 bp) without 5'-triphosphate, and (vi) short double-stranded RNA (23-30 bp) with 5'-monophosphate. RIG-I thus seems promiscuous for a variety of different RNA molecules, very similar to the Toll-like receptors, of which 10 family members are sufficient for the safe detection of the microbial cosmos. In the light of these outstanding publications, it seems an unlikely possibility that there is a fundamental shortcoming in the design of all studies. Looking closely, the only issue that comes to mind is the in vitro transcription technique used by all investigators without confirming the identity of RNA products. This technique, together with the different biological systems used, the lack of dose responses and of proper comparison of different published ligands and controls leave us with more questions than answers as to what the exact RIG-I ligand is, if in fact it exists.

The article describes the first successful application of endoscopically controlled laserlithotripsy in the ENT field in a patient with recurrent purulent sialadenitis of the left submandibular gland due to sialolithiasis. By means of endoscopically controlled laserinduced lithotripsy of salivary gland stones, it was possible to achieve complete stone fragmentation without harming the glandular duct and the gland.

The neuropeptides galanin and pituitary adenylate cyclase-activating peptide (PACAP) are markedly up-regulated in response to peripheral nerve lesion. Both peptides are involved in neuronal differentiation and neurite outgrowth during development. In this study, we investigated the effects of galanin and PACAP on axonal elongation and sprouting by adult rat sensory neurones in vitro and facial motor neurones in vivo. Dissociated rat dorsal root ganglion neurones were plated on laminin substrate and analysed morphometrically. Both the mean axonal length and the number of branch points significantly increased in the presence of galanin or PACAP (2-5 microm). Effects on axonal collateralization were investigated in the rat facial nerve lesion model by direct application of the peptides to collagen-filled conduits entubulating the transected facial nerve stumps. Triple retrograde labelling of brainstem neurones confirmed that the peptides potently induce axonal sprouting of cranial motor neurones. The number of neurones regenerating into identified rami of the facial nerve increased up to fivefold. Biometrical analysis of whisking behaviour revealed that galanin and PACAP impaired the functional outcome when compared with vehicle-treated animals 8 weeks after surgery. In conclusion, although galanin and PACAP have been established as neurotrophic molecules with respect to axonal development and regeneration, their potential as treatments for peripheral nerve lesions appears limited because of the extensive stimulation of collateral axon branching. These branches are misrouted towards incorrect muscles and cause impairment in their coordinated activity.

OBJECTIVES: To assess the subjective and objective performance of the new fine structure processing strategy (FSP) compared to the previous generation coding strategies CIS+ and HDCIS. METHODS: Forty-six adults with a minimum of 6 months of cochlear implant experience were included. CIS+, HDCIS and FSP were compared in speech perception tests in noise, pitch scaling and questionnaires. The randomized tests were performed acutely (interval 1) and again after 3 months of FSP experience (interval 3). The subjective evaluation included questionnaire 1 at intervals 1 and 3, and questionnaire 2 at interval 2, 1 month after interval 1. RESULTS: Comparison between FSP and CIS+ showed that FSP performed at least as well as CIS+ in all speech perception tests, and outperformed CIS+ in vowel and monosyllabic word discrimination. Comparison between FSP and HDCIS showed that both performed equally well in all speech perception tests. Pitch scaling showed that FSP performed at least as well as HDCIS. With FSP, sound quality was at least as good and often better than with HDCIS. CONCLUSIONS: Results indicate that FSP performs better than CIS+ in vowel and monosyllabic word understanding. Subjective evaluation demonstrates strong user preferences for FSP when listening to speech and music.