Universitätsklinik für Hals-, Nasen- und 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: 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.

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.

Adult human neural crest-derived stem cells (NCSCs) are of extraordinary high plasticity and promising candidates for the use in regenerative medicine. Here we describe for the first time a novel neural crest-derived stem cell population within the respiratory epithelium of human adult inferior turbinate. In contrast to superior and middle turbinates, high amounts of source material could be isolated from human inferior turbinates. Using minimally-invasive surgery methods isolation is efficient even in older patients. Within their endogenous niche, inferior turbinate stem cells (ITSCs) expressed high levels of nestin, p75(NTR), and S100. Immunoelectron microscopy using anti-p75 antibodies displayed that ITSCs are of glial origin and closely related to nonmyelinating Schwann cells. Cultivated ITSCs were positive for nestin and S100 and the neural crest markers Slug and SOX10. Whole genome microarray analysis showed pronounced differences to human ES cells in respect to pluripotency markers OCT4, SOX2, LIN28, and NANOG, whereas expression of WDR5, KLF4, and c-MYC was nearly similar. ITSCs were able to differentiate into cells with neuro-ectodermal and mesodermal phenotype. Additionally ITSCs are able to survive and perform neural crest typical chain migration in vivo when transplanted into chicken embryos. However ITSCs do not form teratomas in severe combined immunodeficient mice. Finally, we developed a separation strategy based on magnetic cell sorting of p75(NTR) positive ITSCs that formed larger neurospheres and proliferated faster than p75(NTR) negative ITSCs. Taken together our study describes a novel, readily accessible source of multipotent human NCSCs for potential cell-replacement therapy.

Speech understanding and subjective preference for three different speech coding strategies (spectral peak coding [SPEAK], continuous interleaved sampling [CIS], and advanced combination encoders [ACE]) were investigated in 11 post-lingually deaf adult subjects, using the Nucleus CI 24M cochlear implant system. Subjects were randomly assigned to two groups in a balanced crossover study design. The first group was initially fitted with SPEAK and the second group with CIS. The remaining strategies were tested sequentially over 8 to 10 weeks with systematic variations of number of channels and rate of stimulation. Following a further interval of 3 months, during which subjects were allowed to listen with their preferred strategy, they were tested again with all three strategies. Compound action potentials (CAPs) were recorded using neural response telemetry. Input/output functions in relation to increasing stimulus levels and inter-stimulus intervals between masker and probe were established to assess the physiological status of the cochlear nerve. Objective results and subjective rating showed significant differences in favour of the ACE strategy. Ten of the 11 subjects preferred the ACE strategy at the end of the study. The estimate of the refractory period based on the inter-stimulus interval correlated significantly with the overall performance with all three strategies, but CAP measures could not be related to individual preference of strategy or differences in performance between strategies. Based on these results, the ACE strategy can be recommended as an initial choice specifically for the Nucleus CI 24M cochlear implant system. Nevertheless, access to the other strategies may help to increase performance in individual patients.

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.

Seit der Consensus Conference 1995 ist das Cochlear Implant (CI) als Methode der Wahl bei cochleäer Taubheit etabliert. Mit Hilfe des CI ist es erstmals möglich, den auditiven Sinneskanal nach dem Funktionsverlust des Perzeptionsorganes wieder zu nutzen. Weltweit tragen heute mehr als 30 000 Patienten ein CI. Mittlerweile erscheint es bereits selbstverständlich, die Therapie mit Innenohrimplantaten in das Spektrum der HNO-ärztlichen Behandlung als eine Standardtherapie einzubeziehen.

The goal of treatment for supraglottic cancer is to achieve cure and to preserve laryngeal function. Organ preservation strategies include both endoscopic and open surgical approaches as well as radiation and chemotherapy. The challenge is to select the correct modalities for each patient. Endoscopic procedures should be limited to tumors that can be completely visualized during diagnostic microlaryngoscopy. If complete resection can be achieved, the oncologic results of transoral laser surgery appear to be comparable to those of classic supraglottic laryngectomy. In addition, functional results of transoral laser resection are superior to those of the conventional open approach, in terms of the time required to restore swallowing, tracheotomy rate, incidence of pharyngocutaneous fistulae, and shorter hospital stay. The management of the neck remains of paramount importance, as survival of patients with supraglottic cancer depends more on cervical metastasis than on the primary tumor. Most authors advocate bilateral elective neck dissection. However, in selected cases (T1,T2 clinically negative [N0] lateral supraglottic cancers), ipsilateral selective neck dissection could be performed without compromising survival. The authors conclude that with careful selection of patients, laser supraglottic laryngectomy is a suitable, and often the preferred, treatment option for supraglottic cancer.

Memory B cells (mBCs) are a key to immunologic memory, yet their distribution within lymphoid organs and the individual role of these for mBC functionality remain largely unknown. This study characterized the distribution and phenotype of human (Ag-specific) mBCs in peripheral blood (PB), spleen, tonsil, and bone marrow. We found that the spleen harbors most mBCs, followed by tonsils, BM, and PB, and we detected no major differences in expression of markers associated with higher maturity. Testing the distribution of tetanus toxoid-specific (TT(+)) mBCs revealed their presence in PB during steady state, yet absolute numbers suggested their largest reservoir in the spleen, followed by tonsils. To explore the role of both tissues in the maintenance of reactive B cell memory, we revaccinated controls and splenectomized and tonsillectomized individuals with TT. All donor groups exhibited comparable emergence of anti-TT IgG, TT(+) plasma cells, and TT(+) mBCs in the PB, together with similar molecular characteristics of TT(+) plasma cells. In summary, human mBCs recirculate through PB and reside in different lymphoid organs that do not reflect different mBC maturity stages. The spleen and tonsil, although harboring the largest number of overall and TT(+) mBCs, appear to be dispensable to preserve adequate responsiveness to secondary antigenic challenge.

The effect of vasodilation on simultaneously measured interstitial fluid pressure (IFP, micropuncture) and blood flow (laser-Doppler) in the low compliant pulpal connective tissue was investigated in 10 cats. Vasodilation was induced by electrical stimulation of the tooth after pretreatment with the sympathetic blocker guanethidine. Visualization of the sensory neuropeptides calcitonin gene-related peptide (CGRP) and substance P (SP) was performed using immunocytochemistry. The study was designed to answer the following questions. (1) Does vasodilation promptly increase IFP in low compliant tissues? (2) Does an increase in IFP counteract the blood flow increase? (3) Does repeated electrical stimulation cause reduced staining of CGRP- and SP-immunoreactive nerve fibers in the dental pulp? Electrical stimulation resulted consistently in a nearly synchronous increase in both blood flow and IFP. IFP was nearly doubled, from 6.3 +/- 0.18 mm Hg in control to 11.7 +/- 0.44 mm Hg, whereas blood flow increased by 28%. However, despite continued vasodilation the IFP fell to control level, or even lower, within 1-5 min. The results indicate that the increased IFP will promote fluid absorption into the blood, counteracting a further IFP increase in low compliant tissues during vasodilation. Accordingly, transmural pressure is only transitorily reduced and compression of vessels does not take place. There was considerably less CGRP- and SP-immunoreactive fibers in the stimulated teeth than in the contralateral controls, suggesting that the vasodilation was caused by liberation of these sensory neuropeptides.

Three kava pyrones, the natural compounds (+)-methysticine and (+)-kavain, and the synthetic racemate (+/-)-kavain, were tested concerning their action on in vitro uptake of monoamines in synaptosomes prepared from the cerebral cortex and hippocampus of rats. (+/-)-Kavain and (+)-kavain were found to potently inhibit the uptake of [3H]-noradrenaline. Uptake of [3H]-noradrenaline was inhibited in the following order of potency: (+/-)-kavain = (+)-kavain > (+)-methysticine, whereas none of the kava pyrones efficiently blocked the uptake of [3H]-serotonin. The results indicate a pyrone-specific non-stereo-selective inhibition of the [3H]-noradrenaline uptake which might be responsible for or, at least, contribute to the psychotropic properties of kava pyrones.

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.

Paragangliomas are rare tumors of neural crest origin. They are benign in the majority of cases and are characterized by a strong vascularisation.In the head and neck region they most commonly occur as carotid body tumors. Jugulotympanic and especially vagal paragangliomas are seen less frequently. Complete surgical resection represents the only curative treatment option even though resection of locally advanced tumors regularly results in lesions of the lower cranial nerves and major vessels. Appoximately 30% of all head and neck paragangliomas (HNPs) are hereditary and associated with different tumor syndromes. The paraganglioma syndromes 1, 3 and 4 (PGL 1, 3 and 4) make up the majority of those familial cases. PGL 1 is associated with mutations of the succinate dehydrogenase subunit D (SDHD) gene, PGL 3 is caused by SDHC and PGL 4 by SDHB gene mutations. Multiple HNPs and the occurance of HNPs together with pheochromocytomas are seen in SDHD as well as SDHB mutation carriers. In patients with SDHB mutations the risk for the development of malignant paraganglial tumors is significantly higher compared to SDHC and SDHD patients as well as patients with sporadic tumors. SDHC mutation carriers almost exclusively present with benign HNP that are unifocal in the majority of cases. The role of transmission is autosomal dominant for all three symptoms. Interestingly, there is a "parent-of-origin-dependent-inheritance" in subjects with SDHD gene mutations. This means that the disease phenotype may only become present if the mutation is inherited through the paternal line. We recommend screening for mutations of the genes SDHB, SDHC and SDHD in patients with HNPs. Certain clinical parameters can help to set up the order in which the three genes should be tested.

Aconitum and Delphinium alkaloids are currently under investigation in search for new analgesic and anti-inflammatory drugs. It has been reported that the analgesic compound lappaconitine (LA), a C19 diterpenoid alkaloid from Aconitum sinomontanum nakai is an inhibitor of tetrodotoxin-sensitive, voltage-dependent sodium channels. In the present study we investigated the cardiac effects of LA and its metabolite N-deacetyllappaconitine (DLA) in electrically stimulated left and spontaneously beating right atria isolated from guinea-pig hearts. In all experiments, equieffective concentrations were larger with DLA than with LA. At a stimulation frequency of 2.5 Hz the time constant for the onset of LA effects (tau = 56 +/- 29 min) was markedly larger than the one for DLA effects (tau = 14 +/- 8 min). The compounds exerted a significant negative inotropic action at 0.06 microM (LA) and 0.2 microM (DLA). Asystolia of right atria occurred at 4.5 microM (LA) and 10 microM (DLA). Therefore, cardiotoxicity of LA and DLA was much lower compared to aconitine, which caused arrhythmia at 10 nM in our model. For both alkaloids a use-dependent mode of action could be demonstrated. In addition, preincubation with 0.3 microM LA prevented arrhythmia induced by aconitine or ouabain. We conclude that lappaconitine is a naturally occurring compound with class-I antiarrhythmic action.

Tumours of the neuroendocrine system in the head and neck region are mostly paragangliomas of the glomus tympanicum or jugulare, or of the carotid body. The majority of these tumours are benign, and the coexistence of multiple paragangliomas seems to be rare. Pre-operative embolization and surgery are regarded as primary therapy for these tumours. The treatment regimen in any patient depends on age, general health, hearing status and the function of the lower cranial nerves. Several presentations are possible in which paragangliomas occur as systemic disease. 1. Paragangliomas may occur bilaterally, or, in rare cases, in multiple areas. Pre-operative bilateral angiography is of utmost importance. In case of multicentricity, it might be necessary to proceed without, or just with, unilateral surgery for preservation of adjacent structures. In surgery of jugular vein paraganglioma, we usually perform a modified transmastoidal and transcervical approach with preservation of middle-ear structures and the ossicles. As an alternative or supplement to surgery, radiotherapy or definitive embolization may be used in the treatment of paragangliomas. 2. Paragangliomas may occur as multiple endocrine neoplasia (MEN) syndrome combined with medullary thyroid gland carcinoma, and, facultatively, pheochromocytoma. In these cases, endocrinological examination and magnetic resonance imaging (MRI) of the adrenal region, the thorax and the neck are required for an adequate therapeutic strategy. As MEN may be inherited, family history should be evaluated. 3. Paragangliomas can became malignant and metastasize. Thus, cervical lymph node metastases or distant metastases may occur. We recommend the removal of all ipsilateral lymph nodes and their histological examination.

Functional recovery after facial nerve surgery is poor. Axotomized motoneurons (hyperexcitable upon intracellular current injections, but unable to discharge upon afferent stimulation) outgrow supernumerary branches which are misrouted towards improper muscles. We hypothesized that alterations in the trigeminal input to axotomized electrophysiologically silent facial motoneurons might improve specificity of reinnervation. To test this we compared, in the rat, behavioural, electrophysiological, and morphological parameters after transection and suture of the buccal facial nerve (buccal-buccal anastomosis, BBA) with those after BBA plus excision of the ipsi- or contralateral infraorbital nerve (ION). After BBA, the mystacial vibrissae dropped and remained motionless until 18-21 days post operation (days PO). After BBA plus ipsilateral ION excision, there was no recovery of vibrissae whisking at all. Following BBA plus contralateral ION excision, full restoration of whisking occurred at 7-10 days PO. Electromyography of whiskerpad muscles showed normal waveform and amplitude was also most rapidly restored after BBA plus contralateral ION excision. Neuron counts after retrograde tracing showed that the intact buccal nerve contained axons of the superior (91%) and inferior (9%) buccolabial nerves. After BBA, the superior nerve comprised 56%, the inferior 21%, and 23% of the motoneurons projected within both nerves. After BBA plus ipsilateral ION excision, misdirection worsened and values changed to 48, 39 and 13%, respectively. After BBA plus contralateral ION excision, portions improved to 69, 23 and 8%. We conclude that, by reducing the redundant axon branching, lesion of contralateral ION provides the best conditions for recovery of vibrissae rhythmical whisking after reconstructive surgery on the facial nerve.

BACKGROUND: There is an increasing need for an instrument, which allows to quickly and reliably assess the auditory behaviour of infants and toddlers. SCIENTIFIC QUESTION AND OBJECTIVE: The objective of this study was to develop and validate the "LittlEARS Hearing Questionnaire", a tool for assessing auditory behaviour in children up to 24 months of age. METHODS: Questionnaire construction followed the principles of classical test theory. The psychometric properties of 45 questions on infant auditory behaviour were examined in a sample of 218 parents of normal hearing infants up to age 24 months. Parental responses also served for computing normative values of the development of early auditory behaviour by regression analysis. RESULTS: The final questionnaire contains 35 items, to be answered with either "yes" or "no". The sum of "yes"-answers yields an overall score, which can be compared to age-related normative values in order to appraise the age-appropriateness of the infant's auditory behaviour. The following scale characteristics have been found with the above sample: internal consistency: Cronbach's Alpha = 0.96; reliability: split-half r = 0.88; predictive accuracy: Guttman's Lambda = 0.96; correlation between overall score and age of the children: r = 0.91. CONCLUSION: The "LittlEARS Hearing Questionnaire" is suitable for the quick assessment of a little child's hearing behaviour, e. g. at physical examinations, at the postnatal hearing screening, or when evaluating rehabilitative measures.

(+)-Kavain, a 4-methoxy-alpha-pyrone prepared from Piper methysticum Forst. (Piperaceae), was investigated regarding its assumed antithrombotic action on human platelets which was deduced from its ability to suppress arachidonic acid (AA)-induced aggregation, exocytosis of ATP, and inhibition of cyclooxygenase (COX) and thromboxane synthase (TXS) activity, the latter two effects being estimated from the generation of prostaglandin E2 (PGE2) and thromboxane A2 (TXA2), respectively. Exogenously applied AA (100 mumol/l) provoked a 90% aggregation of platelets, the release of 14 pmol ATP, and the formation of either 220 pg TXA2 or 43 pg PGE2, each parameter being related to 10(6) platelets. An application of (+)-kavain 5 min before AA, dose-dependently diminished aggregation, ATP-release, and the synthesis of TXA2 and PGE2 with IC50 values of 78, 115, 71, and 86 mumol/l, respectively. The similarity of the IC50 values suggest an inhibition of COX by (+)-kavain as primary target, thus suppressing the generation of TXA2 which induces aggregation of platelets and exocytosis of ATP by its binding on TXA2-receptors.

BACKGROUND: T-cells extravasation and CNS parenchyma infiltration during autoimmune neurodegenerative disease can be evoked by local antigen presenting cells. Studying the chemoattracting potential of spinal perivascular macrophages (SPM) during experimental allergic encephalomyelitis (EAE), we observed numerous infiltrates of densely-packed mononuclear cells. Apart from the poor spatial and optical resolution, no differentiation between the resident SPM (mabs ED1+, ED2+) and the just recruited monocytes/macrophages (mab ED1+) was possible. RESULTS: This is why we labeled SPM by injections of different fluoresecent dyes into the lateral cerebral ventricle before induction of active EAE. Within an additional experimental set EAE was induced by an intraperitoneal injection of T-cells specifically sensitized to myelin basic protein (MBP) and engineered to express the green fluorescent protein (GFP). In both experiments we observed a strong activation of SPM (mabs OX6+, SILK6+, CD40+, CD80+, CD86+) which was accompanied by a consistently increased expression of ICAM-1, VCAM-1, and the chemokines MCP-1 and MIP-1alpha. CONCLUSION: These observations indicate that SPM play a role in promoting lymphocyte extravasation.