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10–20% der Bevolkerung leiden an allergischer Rhinitis. Eine umstrittene Therapieoption ist der Gebrauch einer lipidhaltigen Nasensalbe. Um den Effekt dieser Nasensalbe als supportive Therapiemasnahme bei allergischer Rhinitis zu testen, wurde eine bizentrische, prospektive, offene, randomisierte, kontrollierte, klinische Studie durchgefuhrt. 17 Patienten mit Prufpraparat wurden gegen 16 Patienten ohne Anwendung des Prufpraparates getestet. Im Vorher-Nacher-Vergleich zeigte sich in der Prufpraparategruppe eine signifikante, etwa 40%ige Verbesserung der mittleren, relativen Gesamtsymptomatik (Wilcoxon-Mann-Whitney U-Test, p

Background. In the present study we investigated the culturing of fibroblasts on fibrin glue embedded suture nets, to analyse the possibility of using these components in a suture application technique for the closure of a CSF-fistula. Results. Placement of centrally perforated dura pieces on fibrin glue coated surfaces resulted in cellular migration from the dura borders into the defect, resulting in a complete cellular closure of the perforation. Inversion microscopic follow-up during culturing and the Alamar blue-essay found strong growth stimulation for oral mucosa fibroblasts on fibrin glue coated surfaces by insulin and FGF. Three-dimensional fibroblast growth was observed along the suture lines in the presence of fibrin glue. Conclusions. Fibrin glue is an attractive extracellular matrix for cellular migration from the dura which is suited to fibroblast culturing in suture nets. Our findings support the idea of achieving closure of cerebrospinal fluid fistulas by suture application ofautologousfibroblasts and fibrin/ thrombin preparations as a realistic future goal.

Due to shortcomings of conventional hearing aid technology, such as unsatisfactory sound quality due to limited frequency range and undesired distortion, occlusion of the outer ear canal, and acoustic feedback with high amplification, but also psychological aspects of stigmatization, a significant of patients in need of hearing aids are actually not wearing them. Active hearing implants can be distinguished in: (1) impedance transformation implants (ITI), (2) cochlear amplifier implants (CAI), (3) cochlear implants (CI), and (4) brain stem implants (BSI). Whereas ITI are designed for patients with middle ear hearing loss, CAI are intended to restore hearing in patients with inner ear hearing loss. Advantages of CAI may be: (1) improved sound fidelity, (2) no occlusion of the outer ear canal, (3) no feedback, and (4) invisibility. However, not all features are true for every device. CI replace inner ear function in deaf or almost deaf patients. This article gives an overview on the range of active hearing implants to restore hearing and outlines the future use of computer and robot aided surgery.

Juvenile Angiofibrome erscheinen histologisch gutartig, wachsen aber lokal aggressiv. Sie treten uberwiegend bei mannlichen Adoleszenten auf. Als einzige genetische Veranderung sind bisher β-Catenin-Mutationen bei diesem Tumor bekannt. Angiofibromgewebe von 7 Patienten wurde mittels der vergleichenden genomischen Hybridisierung (CGH) auf quantitative Genomveranderungen hin analysiert. In 6 von 7 untersuchten Angiofibromen konnten mit der CGH auf 18 verschiedenen Chromsomen Alterationen nachgewiesen werden. Zugewinne von chromosomalen Abschnitten zeigten sich gehauft auf den Chromosomen 4q, 6q und 8q. In 4 von 7 Fallen zeigte sich ein vollstandiger Verlust des Y-Chromosoms. Die CGH ist zur Analyse chromosomaler Veranderungen bei Angiofibromen geeignet. Mogliche Zielsequenzen fur weitere Genomuntersuchungen, v. a. zum Verlust des Y-Chromosoms, konnten lokalisiert werden.

BACKGROUND Angiofibromas are benign, but locally aggressive tumors occurring nearly exclusively in adolescent males. Pathogenesis of this fibrovascular neoplasm is still unknown. Detection of beta-catenin gene mutations and immunohistochemical localization of beta-catenin only in the nuclei of stromal cells has been proposed as evidence for the stromal cells to be the neoplastic cells in angiofibromas (Abraham et al., 2001). METHODS Paraffin embedded tissue of 13 angiofibromas was analysed immunohistochemically for expression of E-cadherin, N-cadherin, alpha-catenin, beta-catenin and gamma-catenin. RESULTS In all angiofibromas stromal cells showed in their cytoplasm and their nuclei strong immunoreaction for beta-catenin. In 10 out of 13 angiofibromas strong immunoreaction was also observed in endothelial cells covering the irregular lined vascular spaces. While gamma-catenin was detected in 7 out of 13 angiofibromas in the stromal cells and endothelial cells, N-cadherin was found only in the stromal cells in 8 out of 13 angiofibromas. No significant immunoreaction in angiofibromas was seen for E-cadherin and alpha-catenin. CONCLUSIONS Proof of strong beta-catenin-expression in stromal cells and endothelial cells stress possible importance of the APC/beta-catenin-pathway in angiofibromas, but gives no certain evidence for the assumption that stromal cells may be the neoplastic cells. As beta-catenin can increase sensitivity of the androgen receptor, it may be assumed that the increased beta-catenin-expression in angiofibromas is involved in the typical growth stimulus of this tumor in adolescent males.

Vasodilator-stimulated phosphoprotein (VASP) is a member of the ENA/VASP-protein family. VASP is considered to be a crucial factor in the regulation of actin dynamics, which involves processes such as motility and cell adhesion, e.g. in filopodia or growth cones. In these processes zyxin acts as an important partner of VASP and is particularly concentrated at sites where VASP-dependent actin dynamics occur. Based on indirect evidence that actin-mediated dynamics may effect the mechanical properties of the cochlea, we have investigated expression of VASP and zyxin in the postnatal and adult rat cochlea using polymerase chain reaction and Western blot approaches, as well as immunohistochemistry and confocal microscopy. Besides an expected expression in vessels and fibroblasts, VASP and zyxin expression was also observed in pillar cells. Here, the staining was restricted to the head and foot plate of the pillar cells. Onset of VASP expression in pillar cells coincided with the beginning of hearing. In pillar cells, VASP and zyxin were co-localised with pan-actin, suggesting actin-based dynamics in these cochlear cells, which until now were rather presumed to form a highly rigid bridge between the inner and outer sensory cells. Thus, pillar cells may be more dynamically involved in controlling longer-lasting mechanical properties of the cochlea as hitherto presumed.

The detection of binaural interaction is of diagnostic interest in patients with central auditory processing disorders (CAPDs), as binaural hearing tasks are frequently affected in these patients. Owing to the comorbidity associated with disorders such as an attention-deficit hyperactivity disorder, pathological results in subjective tests often show extra-auditory factors such as reduced attention rather than impaired central auditory function. Therefore, objective measures for auditory processing disorders are essential. The binaural interaction component (BIC), which is the arithmetical difference between the sum of the monaurally evoked auditory potentials of each ear and the binaurally evoked brainstem potentials, has been used as an objective measure of binaural interaction in humans. BIC measurements can therefore be considered as a possible diagnostic tool in CAPD patients. One aim of the present study was to examine whether and to what extent BIC measurements are capable of differentiating between normal children and children 'at risk for CAPD'. BIC measurements were performed on 17 children at risk for CAPD and in a group of 25 children with normal results in the central audiometric tests used. Using the presence or absence of clearly demonstrable BIC waveforms as an indication of whether a CAPD is present or not, a sensitivity and specificity of 76% could be achieved. We conclude that BIC measurements might be of some diagnostic value in CAPD patients.

Fistulas of the cerebrospinal fluid are often repaired by insertion of grafts of various kinds. However, current knowledge of wound healing after graft insertion is limited, and only a few animal studies are available. The objective of this study is to test whether an in vitro model is suited to analyze cellular healing aspects after duraplasty and to assess dura substitutes in such conditions in regard to their surface attractiveness for cellular migration from the dura margins. Harvested dura pieces from minipigs were perforated to mimic central dura lesions, placed on various coated surfaces (collagen, laminin, poly-L-lysine) or grafts, and investigated in a cell culture for cellular closure of the perforation. Cellular migration from the dura into the central perforation was noted on collagen-coated surfaces and when defects were filled with collagen gels, but there was no cell growth on surfaces with poly-L-lysine or laminin coating. Immunocytochemistry identified the migrating cells mainly as fibroblasts with some intermingled epithelial cells. Scanning electron microscopy proved cellular closure of defects after dura placement on allogenic non-crosslinked collagen transplants. Less cellular migration was observed on poly-p-dioxanon sheets, while no cells migrated into the central dura perforation after placement on a cartilage substitute. Cell counting indicated enhanced cellular closure of the dura opening after introduction of insulin or fibroblast growth factor (sign test for both: 0.031). Our study succeeded in establishing a cell culture model for duraplasty and indicated cellular migration from the dura borders at the site of the defect during the wound healing process. The cell culture model presented in this report shows that collagen grafts are best suited for duraplasty. In accordance with the immunocytological finding of fibroblast migration from the dura borders additional application of fibroblast-stimulating growth factors accelerated cellular defect closure.

Pathophysiology and treatment of tinnitus still are fields of intensive research. The neuroscientifically motivated Heidelberg Model of Music Therapy, previously developed by the German Center for Music Therapy Research, Heidelberg, Germany, was applied to explore its effects on individual distress and on brain structures. This therapy is a compact and fast application of nine consecutive 50-minutes sessions of individualized therapy implemented over one week. Clinical improvement and long-term effects over several years have previously been published. However the underlying neural basis of the therapy’s success has not yet been explored. In the current study, the therapy was applied to acute tinnitus patients (TG) and healthy active controls (AC). Non-treated patients were also included as passive controls (PTC). As predicted, the therapeutic intervention led to a significant decrease of tinnitus-related distress in TG compared to PTC. Before and after the study week, high-resolution MRT scans were obtained for each subject. Assessment by repeated measures design for several groups (two-way ANOVA) revealed structural gray matter (GM) increase in TG compared to PTC, comprising clusters in precuneus, medial superior frontal areas, and in the auditory cortex. This pattern was further applied as mask for general GM changes as induced by the therapy week. The therapy-like procedure in AC also elicited similar GM increases in precuneus and frontal regions. Comparison between structural effects in TG versus AC was calculated within the mask for general GM changes to obtain specific effects in tinnitus patients, yielding GM increase in right Heschl's gyrus, right Rolandic operculum, and medial superior frontal regions. In line with recent findings on the crucial role of the auditory cortex in maintaining tinnitus-related distress, a causative relation between the therapy-related GM alterations in auditory areas and the long-lasting therapy effects can be assumed.

Sham acupuncture turned out to be more effective than expected. The effect of acupuncture cannot be assessed by optical rhinometry (ORM).In most cases nasal congestion is caused by hypertrophy of the inferior turbinate as a result of allergic and chronic rhinitis. Topical decongestants cause severe side effects. As a consequence, there is an increasing demand for alternative treatment options such as traditional Chinese medicine (TCM).A total of 25 patients with nasal congestion due to hypertrophic inferior turbinate were recruited. The mucosal swelling status of the inferior turbinate was assessed by continuous ORM for 20 min. Patients were asked to score the severity of their nasal congestion on a visual analogue scale (VAS) before and 10 and 20 min after acupuncture. Specific verum acupuncture points related to nasal congestion were tested against non-specific control sham acupuncture points.Sham acupuncture improved VAS scores, whereas ORM measured an increase in nasal swelling. The ORM revealed a quicker onset of the effect of verum acupuncture on the nasal blood flow. Also, verum acupuncture reaches its maximum effect in a shorter time period, so that the net reaction time was much shorter. However, ORM could not prove a decongestant effect of verum acupuncture on inferior turbinate.

Hintergrund. Die totale Pharynxrekonstruktion nach einer Rettungspharyngolaryngektomie bei Rezidivtumoren nach vorangegangener chirurgischer und/oder strahlentherapeutischer Behandlung stellt eine grose Herausforderung fur den Kopf-Hals-Chirurgen dar. Patienten. Wir berichten uber 6 Patienten mit Plattenepithelkarzinomen des Oro-und Hypopharynx und/oder Larynx und totaler Pharynxrekonstruktion. Methode. Bei 3 Patienten erfolgte die Pharynxrekonstruktion 2-zeitig geplant mit Deltopectorallappen, eine Patientin verstarb vor der 2.Operation.Bei 2 Patienten wurde die Pharynxrekonstruktion mit einem zum Rohr geformten myokutanen Pectoralismajor-Lappen durchgefuhrt. Ein Patient erhielt nach Nekrotisierung eines Jejunuminterponats eine Rekonstruktion mit einem gestielten M.-pectoralis-major-Lappen.Zur Fistelpravention wurden bei 3 Patienten Silikontuben und bei den 3 anderen Patienten selbstexpandierende Nitinolstents eingesetzt. Ergebnisse. Von den 5 erfolgreich rekonstruierten Patienten ernahren sich 2 ausschlieslich oral, einer kombiniert oral und uber PEG sowie 2 uber PEG. Schlussfolgerungen. Der Einsatz von Silikontuben und Nitinolstents zur Fistelprotektion hat sich bewahrt. Eine grosere Anzahl von Patienten wurde eine genauere Bewertung dieser Methode ermoglichen.

Hintergrund. Die rasante Entwicklung der Informations- und Kommunikationstechnik bewirkt eine Veranderung aller Lebensbereiche und wird auch in der Medizin die Interaktion zwischen Praxis und Klinik beeinflussen. Methode. Die Arbeit gibt ein Bild uber aktuelle Entwicklungen und Trends der Telemedizin im Einsatz zwischen Praxis und Klinik. Ergebnisse und Schlussfolgerungen. Im Gegensatz zu telemedizinischen Vorreiterstaaten wie Australien liegt in Deutschland ein anderes Anforderungsprofil vor. Nicht die spektakulare Behandlung aus der Ferne, sondern eine zunehmende Verzahnung ist das Ziel des telemedizinischen Einsatzes in Deutschland. Wichtige potenzielle Anwendungen sind der elektronische Arztbrief und die Telekonsultation. Die Einfuhrung der Telemedizin wird praktisch wahrscheinlich eine zunehmende Standardisierung im Gesundheitswesen bewirken.

Prionkrankheiten sind histologisch durch eine spongiforme Enzephalopathie gekennzeichnet. Die fruhen Symptome der Creutzfeldt-Jakob-Krankheit (CJK) und der Variante der Creutzfeldt-Jakob-Krankheit (vCJK) sind unspezifisch. Die sichere Diagnose einer Prionkrankheit ist bisher auch nur durch histopathologische Untersuchungen an Hirngewebe zu stellen. Dies geschieht entweder durch eine Hirnbiopsie oder durch die Sektion post mortem. Deshalb wird an diagnostischen Tests gearbeitet, die mit Liquor oder Blut auskommen. Anders als bei der sporadischen Form der Creutzfeldt-Jakob-Krankheit (CJK), bei der ausschlieslich das zentrale Nervensystem betroffen ist, kommt es bei der Variante der Creutzfeldt-Jakob-Krankheit (vCJK) zu einer Anreicherung des pathologischen Prionproteins im lymphoretikularen System und somit auch der Tonsillen. Damit besteht hier die Moglichkeit einer Tonsillenbiopsie als Alternative zur Hirnbiopsie. Die Diagnosekriterien der CJK und vCJK werden besonders dargestellt.

Hintergrund. Die Domane der Operationsroboter liegt heute in Frasarbeiten an knochernen Strukturen, ihr Einsatz bietet sich z. B. bei den langwierigen und zugleich hochprazisen Frasvorgangen im Bereich der lateralen Schadelbasis an. In jungsten Arbeiten wurden Prozessparameter zur Anlage eines Implantatlagers bspw. fur ein Kochleaimplantat oder fur eine roboterunterstutzte Mastoidektomie ermittelt. Hieraus ergaben sich Optimierungsparameter fur solche Frasvorgange.

Recurrent gain on chromosome 3q26 encompassing the gene locus for the transcription factor SOX2 is a frequent event in human squamous cell carcinoma, including head and neck squamous cell carcinoma (HNSCC). Numerous studies demonstrated that SOX2 expression and function is related to distinct aspects of tumor cell pathophysiology. However, the underlying molecular mechanisms are not well understood, and the correlation between SOX2 expression and clinical outcome revealed conflicting data. Transcriptional profiling after silencing of SOX2 expression in a HNSCC cell line identified a set of up-regulated genes related to cell motility (e.g. VIM, FN1, CDH2). The inverse regulation of SOX2 and aforementioned genes was validated in 18 independent HNSCC cell lines from different anatomical sites. The inhibition of cell migration and invasion by SOX2 was confirmed by constant or conditional gene silencing and accelerated motility of HNSCC cells after SOX2 silencing was partially reverted by down-regulation of vimentin. In a retrospective study, SOX2 expression was determined by immunohistochemical staining on tissue microarrays containing primary tumor specimens of two independent HNSCC patient cohorts. Low SOX2 expression was found in 19.3% and 44.9% of primary tumor specimens, respectively. Univariate analysis demonstrated a statistically significant correlation between low SOX2 protein levels and reduced progression-free survival (Cohort I 51 vs. 16 months; Cohort II 33 vs. 12 months) and overall survival (Cohort I 150 vs. 37 months; Cohort II 33 vs. 16 months). Multivariate Cox proportional hazard model analysis confirmed that low SOX2 expression serves as an independent prognostic marker for HNSCC patients. We conclude that SOX2 inhibits tumor cell motility in HNSCC cells and that low SOX2 expression serves as a prognosticator to identify HNSCC patients at high risk for treatment failure.

Background Dysregulated expression of Kallikrein-related peptidase 6 (KLK6) is a common feature for many human malignancies and numerous studies evaluated KLK6 as a promising biomarker for early diagnosis or unfavorable prognosis. However, the expression of KLK6 in carcinomas derived from mucosal epithelia, including head and neck squamous cell carcinoma (HNSCC), and its mode of action has not been addressed so far. Methods Stable clones of human mucosal tumor cell lines were generated with shRNA-mediated silencing or ectopic overexpression to characterize the impact of KLK6 on tumor relevant processes in vitro. Tissue microarrays with primary HNSCC samples from a retrospective patient cohort (n = 162) were stained by immunohistochemistry and the correlation between KLK6 staining and survival was addressed by univariate Kaplan-Meier and multivariate Cox proportional hazard model analysis. Results KLK6 expression was detected in head and neck tumor cell lines (FaDu, Cal27 and SCC25), but not in HeLa cervix carcinoma cells. Silencing in FaDu cells and ectopic expression in HeLa cells unraveled an inhibitory function of KLK6 on tumor cell proliferation and mobility. FaDu clones with silenced KLK6 expression displayed molecular features resembling epithelial-to-mesenchymal transition, nuclear β-catenin accumulation and higher resistance against irradiation. Low KLK6 protein expression in primary tumors from oropharyngeal and laryngeal SCC patients was significantly correlated with poor progression-free (p = 0.001) and overall survival (p

Objectives Tinnitus is a very common symptom, yet the quest for an effective treatment is challenging. Results from several clinical trials support the notion that neuro-music therapy is an effective means to reduce tinnitus distress with short duration and long lasting effect. However, until now, the effectiveness has not been tested in a controlled trial against an active comparator. Methods The trial was designed as two-center, parallel intervention group controlled study with two intervention groups: Counseling (50 minute individualized personal instruction) or neuro-music therapy (counseling plus eight 50-minute sessions of individualized music therapy). Data of n = 290 patients suffering from chronic tinnitus were analyzed. Outcome measure was the change in Tinnitus Questionnaire Total Scores (TQ) from baseline (admission) to end of treatment. Results Both treatment groups achieved a statistically relevant reduction in TQ scores, though 66% of patients in the music therapy group attained a clinically meaningful improvement compared to 33% in the counseling group. A binary logistic regression revealed two variables significantly influencing therapy outcome: initial tinnitus score and type of therapy with an OR for the music therapy compared to the counseling of 4.34 (CI 2.33–8.09). Conclusions Counseling is an appropriate treatment option with well above chance of improvement. The neuro-music therapy outperformed the counseling. This treatment targets the tinnitus sound itself, is short in duration, intrinsically motivating and easy to operate and thus presents a possible complement to the therapeutic spectrum in chronic tinnitus. The trial was registered at the ClinicalTrials.gov registry (ID: NCT01845155).

Introduction Epistaxis is the most frequent manifestation in hereditary hemorrhagic telangiectasia, in which no optimal treatment exists. It can lead to severe anemia and reduced quality of life. Positive effects of tranexamic acid, an antifibrinolytic drug, have been reported on epistaxis related to this disorder. We sought to evaluate the efficacy of treating nosebleeds in hereditary hemorrhagic telangiectasia with tranexamic acid. Materials and Methods In a randomized, double-blind, placebo controlled, cross-over phase IIIB study, 1 gram of tranexamic acid or placebo was given orally 3 times daily for 3 months for a total of 6 months. Results 22 patients were included in the intention-to-treat analysis. Hemoglobin levels, the primary outcome measure, did not change significantly (p = 0.33). The secondary outcome measure was epistaxis score and patients reported a statistically significant reduction in nosebleeds, equaling a clinically relevant 54% diminution (p = 0.0031), as compared to the placebo period. No severe side effects were observed. Conclusion Tranexamic acid reduces epistaxis in patients with hereditary hemorrhagic telangiectasia. (Clinical trial registration numbers: BfArM 141 CHC 9008–001 and ClinicalTrials.gov NCT01031992 )

Local therapy is practiced for middle and inner ear diseases but is usually restricted to cases of ear drum perforation or repeated invasive intratympanic drug application. Perfusion of drugs on the round window or through the scalae of animals using a pump system suggests that the chronic local drug treatment might also be feasible in humans. However, drug delivery systems that are currently on the market involve repeated reimplantation if they are to be used for long-term drug supply. A bone-anchored, totally implantable micro-drug delivery system (MDS) for patient-controlled drug supply has been developed [Lehner et al., 1997]. In this study, we show the first successful long-term in vivo test of the MDS micro-pump in rats. The process of implantation and first functional tests will be described. The biomaterial used to manufacture the delivery system did not cause any inflammation reaction in any of the 9 animals successfully implanted. After activation of the micro-pump, the drug reservoir and port was found to be fluid-tight. Bolus applications of tetrodotoxin (TTX) to the round window induced a transient decrease of evoked brainstem responses. In 2 animals which carried the MDS for more than 8 months the proper functioning of the pumping device was examined in a 2–3 week interval over a 3 month period. The MDS can be autoclaved even after long-term implantation and can then be reused for subsequent implantations. Designed for life-long implantation in humans, the demonstration of an effective long-term drug supply to the inner ear using the MDS provides an encouraging first step towards future long-term drug treatment of the inner ear in humans.

Telemedicine includes all medical activities in diagnosis, therapeutics, or social medicine undertaken by means of an electronic transfer medium, enabling the transmission of visual and acoustic information over long distances to doctors not personally present at the place of the requested consultation. Most experience with telemedicine applications has been gained in the field of diagnosis (teleconsultation, teleradiology, telepathology) and is expanding to quality control and quality assurance. Decisive for each form of application is its availability, practicability, cost, safety, and especially quality of audiovisual transmission. For telesurgical applications, particularly the use of minimally invasive techniques in otorhinolaryngology, head, and neck surgery, the high quality transmission of audiovisual data in real time is necessary. Rapid expansion and further developments in transmission technologies and networks in the last decade have created several technologies with increased quality and costs. In this paper, we tested different transmission media for audiovisual telecommunication--integrated services digital network (ISDN), Internet, and asynchronous transfer mode (ATM)--using real time video transmission of typical operations in otorhinolaryngology. Their applications, costs, and future perspectives are discussed.

"Telemedicine" is a major new development with great potential for improving health care delivery. It therefore affects each department in medicine. There is a great deal of telemedicine activity around the world. However, the term telemedicine is not clear. It describes all forms of medical information, transferred from a relevant distance by an electronic transfer media. An essential condition for communication is the intelligibility between transmitter and receiver. Because of different transmitting technologies and networks in distinct countries, towns, or even academic institutions, satisfactory contact is not possible. In the last decade, the demand for worldwide audiovisual data transmission has led to the standardization of telecommunication media. Therefore it is no longer necessary to transport medical data (or even patients) by conventional manners, e.g., post, car, or aircraft. Telemedicine for diagnosis and management can be bidirectional in real-time, long-distance videoconferencing, in which the patient consults a specialist located at the remote site, or it can be the transmission of either real-time or pre-recorded images and data to a remote expert, as in teleradiology or telepathology. Another application is the use of videoconference systems in the course of meetings. The remote specialist has the opportunity to take part in the session, e.g., with a lecture. Furthermore, the remote specialist can demonstrate special operative techniques for teleteaching purposes, some of which may be specialities of the particular medical unit, e.g., operation in open NMR, telemanipulation, or telerobotic procedures. In this paper, we describe the use and benefit of a videoconference between the departments of otolaryngology and head and neck surgery of the Universities of Tubingen and Leipzig by means of an "ISDN-based videoconference system". During the meeting, the "operating course for reconstructive surgery in the head and neck", the practicability, reliability, costs and quality were determined and compared with other technologies for audiovisual data transfer.

Der Begriff Telemedizin umfasst alle medizinischen Arbeitsfelder. Durch ein elektronisches Transfermedium wird die Ubertragung visueller und akustischer Informationen von ausreichend hoher Qualitat vermittelt. Hierdurch konnen anderen Orts tatige Spezialisten in die Entscheidungsfindung oder Operation eingebunden werden. In den letzten Jahren hat die Weiterentwicklung der digitalen Datenubertragung z. B. ISDN (integrated service digital network), die Anwendung der Telekommunikation wesentlich verbessert. Eine Echtzeitubertragung visueller und akustischer Information ist in naherer Zukunft durch die Weiterentwicklung neuer Netzwerke wie z. B. ATM (asynchronous transfer modus) zu erwarten. In der minimal-invasiven-HNO-Chirurgie hat die Telemedizin den experimentellen Rahmen in Teilbereichen verlassen und gewinnt zunehmend auch klinische Bedeutung. Die 3 telechirurgischen Anwendungsformen Telekonsultation, Teleassistenz sowie Telemanipulation konnen dabei differenziert werden. Fur die verschiedenen Anwendungsformen werden die moglichen telemedizinischen Ubertragunsarten erklart und diskutiert.

Introduction Mucosal melanomas of the head and neck region are rare, aggressive tumors with a poor prognosis. The standard treatment is radical tumor resection, classical chemotherapies in advanced disease have shown little benefit. Kallikrein-related peptidase 6 (KLK6) belongs to a large family of peptidases, representing secreted chymotrypsin- and trypsin-like serine proteases with diverse expression under physiological and pathological conditions, including common types of human cancer. However, detailed immunohistochemical analyses on skin melanoma tissue sections revealed that KLK6 levels are not elevated due to cellular expression, but rather due to its expression in adjacent keratinocytes and endothelial cells within the tumor microenvironment. The aim of this study is to further classify mucosal melanomas molecularly with regard to KLK6 and to identify new possible targets or biomarkers. Material and methods In cooperation with the Departments of Otorhinolaryngology at Technical Medical Center Munich and Essen, we were able to identify 22 patients with mucosal melanoma, medical history, tumor stage and paraffin-embedded tissue was available. Immunohistochemical staining with Kallikrein-related peptidase 6 was done, the results were correlated to the clinical data and course. Results Tumors were located endonasally, within the nasal sinuses and the eyes in 10/22, 10/22 and 2/22. All patients had undergone surgery; in 34% of the cases adjuvant radiation was administered and 14% were given systemic interferon-therapy. The probability of one-year-survival was 81.8% (18/22) and of five-year-survival 50% (5/10). The mean overall-survival was 51 months, the mean recurrence-free-survival 26 months. Immunohistochemical analyses resulted in an expression of KLK6 in 72.7% of the analyzed cases. Cutaneous melanoma samples examined as reference showed weak staining in 33%. Additional to the cytoplasmatic staining in mucosal melanoma, nuclear staining was observed in 6 cases. Cross table analysis revealed that low or no KLK6 expression was significantly correlated with local tumor recurrence. Conclusion The investigated Kallikrein-related peptidase 6 shows high expression in mucosal melanoma and – in contrast to most other human malignancies where KLK6 has been described before – a significant correlation of high KLK6 expression and low risk of local tumor recurrence.

Fur die Mehrzahl der Innenohrschwerhorigen kann selbst mit modernster Horgeratetechnik keine die Patienten zufriedenstellende Horrehabilitation erzielt werden. Fur diese grose Zahl von Betroffenen ohne adaquate Versorgung sind teilimplantierbare Horgerate entwickelt worden, die konventionellen Horgeraten besonders bei Klangtreue und Sprachverstandlichkeit deutlich uberlegen sein konnen. Allerdings konnen sie den Kranken durch ausen an Kopf oder Korper zu tragende Teile stigmatisieren. Auch nutzen sie die Storschallunterdruckung als auch die auditorische Raumorientierung mittels des auseren Gehorgangs noch nicht aus. Hier berichten wir uber die ersten Implantationen eines neuartigen, vollstandig implantierbaren Horsystems (TICA® LZ 3001) bei Innenohrschwerhorigen. Es nimmt den Schall uber ein trommelfellnahes Mikrophon durch die intakte Gehorgangshaut auf. Ein retroaurikular subkutan implantierter, mehrkanaliger digital programmierbarer Audioprozessor verarbeitet das Signal und gibt es uber einen piezoelektronischen Wandler im Mastoid an den Amboskorper weiter. Energie wird durch eine implantierbare Batterie bereitgestellt. Implantierte Patienten empfinden das Gehorte als verzerrungsfrei und transparent. Sie verstehen Sprache und empfinden Musik besser als ohne Implantat. Insbesondere im Storlarm kann z.T. ein erheblich verbessertes Sprachverstandnis erreicht werden. Die bisherigen Ergebnisse ermutigen, weitere Implantationserfahrungen mit dem vollstandig implantierbaren Horsystem zu sammeln.

Since the discovery of distortion product otoacoustic emissions (DPOAE) there has been a controversial discussion about their cochlear generation sites. Suppression experiments suggest that the place near f2 is the main generation site. On the other hand, the fact that DPOAE can be perceived subjectively indicates that there is also a cochlear excitation at the place of 2f1−f2 resulting in a stimulus frequency otoacoustic emission (SFOAE). The contribution of this SFOAE to the overall emission is still unknown. Different studies showed contradictory results. We demonstrate a secondary generator by successive suppression of the SFOAE with a sine wave close to the frequency 2f1−f2. Suppression growth functions (SGF) showed a three-step behavior. For low suppressor levels, the emission either decreased or increased when increasing the suppressor. For intermediate suppressor levels, DP amplitude was constant and independant of suppressor level. For high suppressor levels, the emission always decreased with further increase of the suppressor. The behavior of the SGF in the first section depends on the fine structure of the DP-gram, which shows minima and maxima. Emissions at a maximum decreased while emissions at a minimum increased in the first section of the SGF. We conclude that the fine structure of the DP-gram is produced by alternate constructive and destructive interference of the two generators. By adding a third tone near 2f1−f2 the SFOAE and thus the interference are suppressed. The fine structure of the DP-gram vanishes and the resulting DP-gram should be more closely related to the cochlear status near f2.

BACKGROUND Characteristic features of cholesteatoma of the middle ear are destruction of the bone and a high tendency for recurrent disease. The choice of surgical procedure is determined by audiological results and the rate of recurrent cholesteatoma. PATIENTS One hundred fifty patients who underwent primary cholesteatoma surgery were investigated 3-5 years postoperatively. Preoperative and postoperative audiological results and rate of revision surgery were compared for the respective surgical procedures. All cholesteatomas were treated with an open surgical technique. The lateral attic walls and cholesteatomas were removed. RESULTS Cholesteotoma recurred in 15 patients (10%). Primary reconstruction of the ossicular chain with a tympanoplasty (type III) was performed in 98 patients in the first operation. Approximately 80% of patients treated with a type III tympanoplasty had a maximum postoperative air-bone gap of 20 dB in the main speech range, depending on the frequency. In about 50% of patients, this value was 10 dB or less. Comparison of preoperative and postoperative conductive hearing loss between 250 Hz and 8000 Hz revealed an improvement (p < 0.05) of 10 dB (500 Hz, 3000 Hz, 4000 Hz) and 15 dB (250 Hz, 1500 Hz, 2000 Hz, 8000 Hz). CONCLUSIONS In our opinion, a second look operation should be performed in cases where a large cholesteatoma cannot be removed with sufficient reliability. This applies especially to a cholesteatoma in the oval window. Here, we suggest second-look surgery after one year.

Ergebnisse von 192 an der Universitats-HNO-Klinik Tubingen zum ersten Mal wegen einer chronischen Schleimhauteiterung behandelten Patienten wurden retrospektiv erfast. Der Beobachtungszeitraum betrug minimal 1 bis maximal 4,5 Jahre. Die Gehorknochelchenkette war bei 43 Ohren (22,4%) unterbrochen. Sie wurde mit dem patienteneigenen Ambos (31 Falle) und Hammer (12 Falle) rekonstruiert. Rezidivdefekte des Trommelfells traten in 40 Fallen (20,8%) auf. Die meisten Rezidive traten bei Patienten im mittleren Lebensalter auf. Die in der Literatur oft als Problemfall geschilderten Kinder hatten in der eigenen Untersuchung vergleichsweise weniger Rezidivdefekte (14%). Das Material mit der hochsten Quote an Rezidivdefekten war die Temporalisfaszie mit 28,6%. Nach dem Verschlus des Trommelfells mit Perichondrium oder einem Tragusknorpel-Perichondrium-Transplantat gab es nur 6,8 bzw. 4,8% Rezidive. Bei 1,5 kHz hatten 3–6 Monate postoperativ 62,7% aller Patienten eine Schalleitungskomponente von 10 dB oder weniger. Eine Schalleitungskomponente von 20 dB oder weniger hatten bei derselben Frequenz 91,2% der Patienten. Das hauptsachliche Problem bei der chronischen Schleimhauteiterung ist weniger die Rekonstruktion der Schalleitungskette als vielmehr der dauerhafte Verschlus des Trommelfells. Hier erbringt das Knorpel-Perichondrium-Transplantat die besten Resultate und ist deshalb zumindest fur Patienten mit ungunstigen Mittelohrverhaltnissen zu empfehlen. Ein langfristiger Trommelfellverschlus wurde auch bei Kindern (≤15 Jahre) erreicht. Deshalb raten wir zu einer fruhen Operation, um den Kindern ein normales Leben zu ermoglichen.

Distorsionsprodukte otoakustischer Emissionen (DPOAE) entstehen unzweifelhaft im Uberlappungsbereich der Wanderwellen fur die beiden Primartone f1 und f2 (primarer Entstehungsort). Da DPOAE subjektiv wahrnehmbar sind, ist davon auszugehen, das auch am Ort 2f1–f2 der kochleare Verstarker aktiviert wird, wodurch eine Stimulusfrequenzemission (SFOAE) entsteht (sekundare Emissionsquelle). In Suppressionsexperimenten untersuchten wir den Ort der postulierten 2. Emissionsquelle mit einem zusatzlichen 3. Ton (Suppressor), dessen Frequenz 25 Hz oberhalb von 2f1–f2 lag. Die Distorsionsprodukt(DP-)amplitude veranderte sich mit wachsender Amplitude des Suppressors (−20 bis 80 dB SPL). Dieser Suppressionseffekt erscheint jedoch unterschiedlich in Abhangigkeit von der Position des supprimierten Distorsionsproduktes innerhalb der DP-Feinstruktur. Bei einem Maximum der Feinstruktur reduzierte ein leiser Suppressor (

Kurzlich konnte von unserer Arbeitsgruppe ein implantierbarer piezoelektrischer Horgeratwandler vorgestellt werden, der aufgrund seiner Eigenschaften fur die Implantation bei Innenohrschwerhorigen geeignet ist. Dabei ubertragt der Wandler keinen Schall, sondern mikromechanische Schwingungen auf das Gehor. Die Wirksamkeit dieses Wandlerimplantats zur direkten Ubertragung von Schwingungen im horbaren Frequenzbereich uber die Gehorknochelchenkette auf das Innenohr oder direkt in das Vestibulum des Innenohrs wurde tierexperimentell an 10 Katzenohren untersucht. Nach praoperativer (akustischer) BERA-Schwellenbestimmung wurde das Mittelohr eroffnet und der piezoelektrische Wandler an Gehorknochelchen oder die Perilymphe angekoppelt. Dadurch konnten bei Stimulation am Umbo, langem Ambosfortsatz, Steigbugelkopfchen und an der Fusplatte sowie im Vestibulum die BERA-Schwellen an 8 Katzenohren erfolgreich aufgenommen werden. Durch einen Vergleich der akustischen mit der mikromechanischen Horschwelle konnte eine Korrelation zwischen den Reizpegeln der akustischen und mechanischen Stimulation gefunden werden. Es zeigte sich, das mit einer elektrischen Ansteuerspannung des angekoppelten Wandlers von 1 VRMSaquivalente Schalldruckpegel vor dem Trommelfell zwischen 100 und 128 dB SPL erreicht wurden. Zur Beurteilung des Horeindrucks wurden neben den Horschwellen die Latenzen der fruhen akustisch und mechanisch evozierten Potentiale (Wellen P1 bis P5) reizpegelabhangig analysiert und einander gegenubergestellt. Die Auswertung erfolgte an 4 normalhorenden Ohren, bei denen der piezoelektrische Wandler am langen Ambosfortsatz angekoppelt war. Die Mittelwerte der Latenzen und deren Streuungen zeigten sehr gute Ubereinstimmungen zwischen beiden Stimulationsarten. Sie waren nahezu deckungsgleich bei Zuordnung eines aquivalenten Schalldruckpegels von 100 dB SPL zur maximal verwendeten elektrischen Ansteuerspannung von 1 VRMS. Nach der in vitro-Testung [22, 23] und der hier vorgelegten in vivo-Untersuchung besitzt der Wandler damit fundamentale Eigenschaften, die es sinnvoll erscheinen lassen, den Prototypen zu einem Bauteil eines implantierbaren Horgerats fur Innenohrschwerhorige weiterzuentwickeln.

During routine middle ear surgery prototypes of implantable piezoelectric hearing aid transducers were coupled to the ossicular chain of 28 patients. Pure tone thresholds in a broad frequency range (250 Hz-8 kHz) and perception of music were the basis of psychoacoustic evaluation of the transfer properties of the prototypes in this human study. The piezoelectric transducer reached an equivalent transducer sound-pressure level of up to 145 dB SPL and frequencies of 10 kHz. The dynamics for music reached 32 dB, which was identical with the results of the preoperative investigations using hi-fi headsets (33 dB). The low nonlinear distortions of around 0.1% and the frequency range up to 10 kHz are reflected in the positive evaluation of sound quality by 84% of the patients involved. The study is the basis for realizing a piezoelectric transducer designed for routine clinical implantations. The transducer is thought to be part of a totally implantable future hearing aid for rehabilitation of moderate and severe sensory neural hearing loss predominantly in the middle and high frequency range.

Musical training positively influences the cortical plasticity of the brain and has proven to be effective in treating chronic tinnitus.A neuro-music therapy concept, the "Heidelberg Neuro-Music Therapy" treatment was developed and evaluated.A prospective, cross-sectional design was used.N = 135 patients (mean age 47 years) with chronic, tonal tinnitus attended a standardized protocol for Neuro-Music Therapy (either "standard therapy" ST or "compact therapy" CT). The results were compared to a cognitive behavioral placebo music therapy procedure (PT). Tinnitus distress was assessed using the German version of the Tinnitus-Questionnaire (TQ) at admission, at discharge and six months after therapy. Changes were assessed statistically and by means of clinical significance.TQ scores significantly improved - independent of group allocation. But more than 80% of the music therapy patients (both ST and CT) revealed a reliable improvement ("responder") compared to 44% in the PT group. Therapy impact seems to be lasting since TQ scores remained stable until follow-up at six months.The "Heidelberg Neuro-Music Therapy" is a method with fast onset and long lasting effect for patients with "tonal" tinnitus. A number of potential working factors accounting for the treatment success are highlighted.

In the present study a music therapeutic intervention according to the ‘Heidelberg Model’ was evaluated as a complementary treatment option for patients with acute tinnitus whom medical treatment only brought minimal or no improvement. The central question was if music therapy in an early phase of tinnitus was able to reduce tinnitus symptoms and to prevent them from becoming chronical. 23 patients with acute tinnitus (6-12 weeks) were included in this study and took part in our manualized short term music therapeutic treatment which lasted ten consecutive 50-minutes sessions of individualized therapy. Tinnitus severity and individual tinnitus related distress were assessed by the Tinnitus Beeinträchtigungs-Fragebogen (i.e. Tinnitus Impairment Questionnaire, TBF-12) at baseline, start of treatment, and end of treatment. Score changes in TBF-12 from start to end of the treatment showed significant improvements in tinnitus impairment. This indicates that this music therapy approach applied in an initial stage of tinnitus can make an important contribution towards preventing tinnitus from becoming a chronic condition.

Aberrant expression of the receptor for advanced glycation end products (RAGE) and its ligands, such as S100/Calgranulins, has been demonstrated in squamous cell carcinomas of the upper aerodigestive tract. However, the question whether RAGE signaling is causally linked with neoplastic transformation of keratinocytes in mucosal epithelia has not been addressed so far. We used the well-established mouse model of 4-nitroquinoline-1-oxide (4-NQO) induced tumorigenesis to investigate tumor development in control and RAGE-deficient (Rage(-/-)) animals. Although 4-NQO induced lesions of the tongue and the esophagus showed strong induction of the RAGE ligands S100a8 and S100a9, we did not observe any significant difference in tumor incidence or multiplicity between control and Rage(-/-) mice. Furthermore, detailed analysis of tumor sections by histological and immunohistochemical staining revealed no difference in either the size or histological architecture of dysplastic lesions, tumor cell proliferation, or the number of inflammatory immune cells in the tumor microenvironment. Finally, we detected induced transcript and protein levels of the Toll-like receptor 4 (Tlr4) in 4-NQO induced lesions, suggesting that signaling via the S100-Tlr4 axis may compensate for the lack of RAGE in early stages of tumor development. Our data demonstrate that RAGE is dispensable in the onset of genotoxic induced oral and esophageal squamous cell carcinoma and provide evidence for an alternative pathway of S100-Calgranulin signaling via Tlr4.

High-risk types of human papilloma virus (HPV) are increasingly associated with oropharyngeal squamous cell carcinoma (OPSCC). Strikingly, patients with HPV-positive OPSCC are highly curable with ionizing radiation and have better survival compared with HPV-negative patients, but the underlying molecular mechanisms remain poorly understood. We applied an array-based approach to monitor global changes in CpG island hypermethylation between HPV-negative and HPV-positive OPSCCs and identified a specific pattern of differentially methylated regions that critically depends on the presence of viral transcripts. HPV-related alterations were confirmed for the majority of candidate gene promoters by mass spectrometric, quantitative methylation analysis. There was a significant inverse correlation between promoter hypermethylation of ALDH1A2, OSR2, GATA4, GRIA4, and IRX4 and transcript levels. Interestingly, Kaplan-Meier analysis revealed that a combined promoter methylation pattern of low methylation levels in ALDH1A2 and OSR2 promoters and high methylation levels in GATA4, GRIA4, and IRX4 promoters was significantly correlated with improved survival in 3 independent patient cohorts. ALDH1A2 protein levels, determined by immunohistochemistry on tissue microarrays, confirmed the association with clinical outcome. In summary, our study highlights specific alterations in global gene promoter methylation in HPV-driven OPSCCs and identifies a signature that predicts the clinical outcome in OPSCCs.

Purpose: Previous research on psychosocial adaptation of sensory-impaired older adults has focused mainly on only one sensory modality and on a limited number of successful aging outcomes. We considered a broad range of successful aging indicators and compared older adults with vision impairment, hearing impairment, and dual sensory impairments and without sensory impairment. Design and Methods: Data came from samples of severely visually impaired (VI; N = 121), severely hearing-impaired (HI; N = 116), dual sensory-impaired (DI; N = 43), and sensory-unimpaired older adults (UI; N = 150). Participants underwent a wide-ranging assessment, covering everyday competence, cognitive functioning, social resources, self-regulation strategies, cognitive and affective well-being, and 4-year survival status (except the DI group). Results: The most pronounced difference among groups was in the area of everyday competence (lowest in VI and DI). Multigroup comparisons in latent space revealed both similar and differing relationship strengths among health, everyday competence, social resources, self-regulation, and overall well-being, depending on sensory status. After 4 years, mortality in VI (29%) and HI (30%) was significantly higher than in UI (20%) at the bivariate level, but not after controlling for confounders in a multivariate analysis. Implications: A multidimensional approach to the understanding of sensory impairment and psychosocial adaptation in old age reveals a complex picture of loss and maintenance.

Background: Whereas a tubular adenoma is a unique finding within the paranasal sinuses, intestinal adenocarcinomas are especially in patients with long-term exposure to wood dust, common tumours in this location. Case: In a 65 year old joiner endonasal sinus surgery performed to treat suspected chronic pansinusitis brought up by chance the histological finding of a tubular adenoma. As the patient at first refused surgical revision, but magnetic resonance imaging during follow-up revealed evidence for a space occupying lesion affecting the ethmoid and sphenoid sinuses revision surgery took place one year later. Histopathological evaluation now found a papillary adenocarcinoma. Clinical follow-up and magnetic resonance imaging one year after second surgery found no evidence for tumour recurrence. Conclusions: Progression of a tubular adenoma to an adenocarcinoma like in the adenoma-carcinoma model well known for colorectal carcinomas has so far not been observed within the paranasal sinuses. But, an adenocarcinoma already present at the time of first surgery can not be ruled out completely in the presented case as histopathological evaluation may have failed to detect an adenocarcinoma in the available specimens after first surgery. Either malignant transformation of a tubular adenoma had occurred or proof of an adenocarcinoma has failed with misdiagnosis of a tubular adenoma. A tubular adenoma as well as an adenocarcinoma require complete resection and careful clinical and radiological follow-up to avoid adenocarcinoma development from a tubular adenoma or to detect an adenocarcinoma by histological evaluation of the whole specimen.

This article reports on a 62-year-old man, who presented with cervical mass and rather nonspecific symptoms. The medical history and clinical workup initially favored a malignant disease such as a carcinoma of unknown primary as the underlying cause. Eventually, the patient was diagnosed with a granulomatous lymphadenitis caused by Francisella tularensis subsp holarctica. Tularemia is a rare disease in Western Europe and can present in multiple ways encompassing almost asymptomatic infections and fatal disease. A rapid diagnosis is often hampered by nonspecific symptoms and the generally low prevalence and incidence of this disease in endemic countries. This case report also provides a comprehensive review of the literature on cervical tularemia and discusses the differential diagnoses.

Facial nerve preservation and oncological safety are crucial in surgery of parotid tumors. An unexpected histopathologic diagnosis of a malignant parotid tumor, however, may unfavorably require a second, more radical surgery. The aim of this study was to find out whether the assessment of serological tumor markers in parotid saliva might have some diagnostic significance in the preoperative differentiation between benign and malignant parotid lesions. STUDY DESIGN, SETTING, PATIENTS, AND METHODS: In a prospective pilot study performed at a university medical center in 28 patients with a unilateral parotid tumor, 7 serological tumor markers established in the clinical routine were quantitatively assessed in parotid saliva collected simultaneously on both sides after stimulation. The results were correlated with the histopathological diagnosis.Of the 4 investigated tumors that were malignant neoplasms, 3 had a sufficient quantity of saliva available for tumor marker measurements. Carbohydrate antigen 19-9 (CA 19-9) consistently revealed high levels compared with the unaffected side in all malignant tumors, thus allowing malignant tumors to be differentiated from benign lesions.The results of this pilot study are encouraging, showing that preoperative tumor marker investigation in saliva from parotid glands is feasible and merits further investigation. CA 19-9 might be a valuable new diagnostic tool in the preoperative differentiation between malignant and benign parotid tumors and should be investigated in a larger number of patients.

Background Surgery after (chemo)radiation (RCTX/RTX) is felt to be plagued with a high incidence of wound healing complications reported to be as high as 70%. The additional use of vascularized flaps may help to decrease this high rate of complications. Therefore, we examined within a retrospective single-institutional study the peri--and postoperative complications in patients who underwent surgery for salvage, palliation or functional rehabilitation after (chemo)radiation with regional and free flaps. As a second study end point the Karnofsky performance status (KPS) was determined preoperatively and 3 months postoperatively to assess the impact of such extensive procedures on the overall performance status of this heavily pretreated patient population. Findings 21 patients were treated between 2005 and 2010 in a single institution (17 male, 4 female) for salvage (10/21), palliation (4/21), or functional rehabilitation (7/21). Overall 23 flaps were performed of which 8 were free flaps. Major recipient site complications were observed in only 4 pts. (19%) (1 postoperative haemorrhage, 1 partial flap loss, 2 fistulas) and major donor site complications in 1 pt (wound dehiscence). Also 2 minor donor site complications were observed. The overall complication rate was 33%. There was no free flap loss. Assessment of pre- and postoperative KPS revealed improvement in 13 out of 21 patients (62%). A decline of KPS was noted in only one patient. Conclusions We conclude that within this (chemo)radiated patient population surgical interventions for salvage, palliation or improve function can be safely performed once vascularised grafts are used.

Oral squamous cell carcinoma (OSCC) is a challenging disease with a high mortality rate. Natural products represent a valuable source for the development of novel anticancer drugs. We investigated the cytotoxic potential of essential oil from the leaves of a medicinal plant, Levisticum officinale (lovage) on head and neck squamous carcinoma cells (HNSCC).Cytotoxicity of lovage essential oil was investigated on the HNSCC cell line, UMSCC1. Additionally, we performed pharmacogenomics analyses.Lovage essential oil extract had an IC₅₀ value of 292.6 μg/ml. Genes involved in apoptosis, cancer, cellular growth and cell cycle regulation were the most prominently affected in microarray analyses. The three pathways to be most significantly regulated were extracellular signal-regulated kinase 5 (ERK5) signaling, integrin-linked kinase (ILK) signaling, virus entry via endocytic pathways and p53 signaling.Levisticum officinale essential oil inhibits human HNSCC cell growth.

Oral cavity squamous cell carcinoma (OCSCC) accounts for 2% to 3% of all malignancies and has a high mortality rate. The majority of anticancer drugs are of natural origin. However, it is unknown whether the medicinal plant Thymus vulgaris L. (thyme) is cytotoxic towards head and neck squamous cell carcinoma (HNSCC).Cytotoxicity of thyme essential oil was investigated on the HNSCC cell line, UMSCC1. The IC₅₀ of thyme essential oil extract was 369 μg/ml. Moreover, we performed pharmacogenomics analyses.Genes involved in the cell cycle, cell death and cancer were involved in the cytotoxic activity of thyme essential oil at the transcriptional level. The three most significantly regulated pathways by thyme essential oil were interferon signaling, N-glycan biosynthesis and extracellular signal-regulated kinase 5 (ERK5) signaling.Thyme essential oil inhibits human HNSCC cell growth. Based on pharmacogenomic approaches, novel insights into the molecular mode of anticancer activity of thyme are presented.

We reasoned that micro-dissection of tumour cells for protein expression studies should be omitted since tumour-stroma interactions are an important part of the biology of solid tumours. To study such interactions in head and neck squamous cell carcinoma (HNSCC) development, we generated reference protein spectra for normal squamous epithelium and connective tissue by SELDI-TOF-MS. Calgranulins A and B, Annexin1 and Histone H4 were found to be strongly enriched in the epithelium. The alpha-defensins 1-3 and the haemoglobin subunits were identified in the connective tissue. Tumour-distant epithelia, representing early pre-malignant lesions, showed up-regulated expression of the stromal alpha-defensins, whereas the epithelial Annexin 1 was down-regulated. Thus, tumour microenvironment interactions occur very early in the carcinogenic process. These data demonstrate that omitting micro-dissection is actually beneficial for studying changes in protein expression during development and progression of solid tumours.

International audience; Vinblastine and vincristine are dimeric indole alkaloids derived from (formerly: ). Their monomeric precursor molecules are vindoline and catharanthine. While vinblastine and vincristine are well-known mitotic spindle poisons, not much is known about vindoline and catharanthine. Vindoline and catharanthine showed weak cytotoxicity, while vinblastine, vincristine, and the semisynthetic vindesine and vinorelbine revealed high cytotoxicity towards cancer cells. This may reflect a general biological principle of poisonous plants. Highly toxic compounds are not only active towards predators, but also towards plant tissues. Hence, plants need mechanisms to protect themselves from their own poisons. One evolutionary strategy to solve this problem is to generate less toxic precursors, which are dimerized to toxic end products when needed. As shown by molecular docking and biochemical approaches, vinblastine, vincristine and vinorelbine bound with high affinity to α?β-tubulin and inhibited tubulin polymerization, whereas the effects of vindoline and catharanthine were weak. Similarly, vinblastine produced high fractions of mono- and multipolar mitotic spindles, while vindoline and catharanthine did only weakly affect bipolar mitotic spindle formation. Inhibition of centrosomal clustering represents a treatment novel strategy leading to multipolar spindle formation and apoptosis. This has been shown for vinblastine by us for the first time. P-glycoprotein-overexpressing multidrug-resistant CEM/VCR1000 cells were highly resistant towards vincristine and cross-resistant to vinblastine, vindesine, and vinorelbine, but not or only weakly cross-resistant to vindoline and catharanthine. In addition to tubulin as primary target, microarray-based mRNA signatures of responsiveness of these compounds have been identified by COMPARE and signaling pathway profiling.

The new length-adjustable titanium prosthesis can give good results in terms of hearing results in ossiculoplasty. The possibility to readjust the length intraoperatively was seen as a good feature.Hearing results of ossiculoplasty with a newly designed prosthesis in 14 patients were evaluated. The prosthesis is designed to allow adjustment of length in situ.A retrospective pilot study was carried out, comparing the preoperative and postoperative audiological and clinical results with an age- and pathology-matched group. The setting was the Department of Otolaryngology at the University of Heidelberg Medical Center, a tertiary referral center. In all, 14 patients underwent tympano-ossiculoplasty in which autologous reconstruction was not an option. The ossiculoplasty was performed as a therapeutic measure with the new titanium prosthesis. We evaluated the air–bone gap closure as established from preoperative and postoperative audiograms. We also looked at the clinical aspect of the tympanic membrane.The average air–bone gap came to a closure within 15 dB in 43% of the cases (6 of 14 patients). No re-perforations or extrusions of the prostheses were observed.

Das Horen spielt fur uns Menschen eine ganz uberragende Rolle. Und dies in jedem Lebensalter. Leider nimmt jedoch das Ausmas einer Horminderung im Laufe des Lebens eher zu. Dieses fuhrt zu einem zunehmenden Verlust an Kommunikation. Bedingt durch diesen Horverlust kommt es dann oft zur Erschwerung der Verstandigung bis hin zur Vereinsamung. Dies gerade, wenn die Betroffenen merken, dass sie nicht mehr an Gesprachen teilnehmen konnen, nachfragen mussen, und damit sich und anderen (zu unrecht!) „dumm“ vorkommen. Die Bewaltigung alltaglicher Lebensaufgaben wird so erheblich schwieriger. Und wenn schlieslich ein nahezu vollstandiger Horverlust vorliegt, ist das Risiko des Autonomieverlustes gros. Aber auch ohne ihn ist der Verlust an Lebensqualitat erheblich und belastend.

Between 1985 and 1991, 36 patients with glomus tumors of the temporal bone were operated. More than 60% of the patients presented with an advanced disease (Class C and D) according to the initially discret and slowly progressive clinical signs. Pulsatile tinnitus, hearing loss and paresis of the lower cranial nerves IV to XII were most often found. The management of the patients requires a complete surgical resection with different approaches depending on the extension of the tumor. High resolution CT of the temporal bone and selective angiography of the tumor feeding vessels proved as reliable and necessary imaging tools to determine the size of the tumor and thereby the surgical procedure. Class A tumors (n = 4) were completely resected by an enaural transmeatal approach. Class B tumors (n = 10) were removed completely in all cases by a combined transmeatal-transmastoid approach. A conductive hearing loss in 2 cases and transient facial paresis in one case were observed. Class C tumors (Glomus jugulare tumors, n = 16) required an infratemporal fossa approach type A. A complete resection was achieved in 87.5%. Class D tumors (n = 6) with intracranial extension were managed in a two stage otoneurosurgical procedure. Due to the tumor size and the required surgical procedure a higher incidence of functional lesions (combined hearing loss, vertigo, cranial nerve pareses) was observed. A facial paresis occurred in all cases but was transient in most of them. The results show that functional conservation surgery for glomus tumors of the temporal bone is only possible in Class A and B and some of the Class C tumors. This requires an early diagnosis.

The active vibration of the basilar membrane as well as evoked otoacoustic emissions (EOAE) are probably based on the motile properties of cochlear outer hair cells (OHC). In the present study we examined the effects of contralateral acoustic stimulation on ipsilateral EOAE and thereby the active cochlear micromechanics. Contralateral white noise with intensities below 30 dB HL enhanced the EOAE amplitude, whereas higher sound levels reduced the evoked acoustic emissions. Similar effects of contralateral acoustic stimuli on ipsilateral EOAE were observed in patients with a conductive hearing loss. However, the required sound levels were higher compared to probands with normal hearing. In controls with unilateral deaf patients white noise up to 60 dB HL did not alter the EOAE amplitude. We concluded, that in patients with normal hearing or unilateral conductive hearing loss, effects of contralateral acoustic stimulation on evoked ipsilateral sound emissions may be due to the activation of crossed olivo-cochlear efferents reaching the OHCs.