[Impact of Microsurgical Exstirpation of Vestibular Schwannomas on the Sense of Taste]. / Effekt der mikrochirurgischen Entfernung von Vestibularisschwannomen auf das Schmeckvermögen.

Patients with single sided vestibular schwannoma may report about a taste dysfunction apart from the well known cardinal symptoms. Very few data are published so far on that topic. The aim of this study was to investigate the influence of microsurgery for vestibular schwannomas on taste perception prospectively using a well validated taste test. 25 patients could be included in the study. No ageusia was claimed by the patients. In average a decrease of the taste score postoperatively could be detected on the tumor as well as on the non treated side. The differences were not statistically significant. But a subgroup of » of the subjects revealed a new onset of side difference in the taste score that was not present before surgery. In all those cases the treated side showed a clinically significant reduced taste score of 6,2 in average. Within this subgroup the temporal access was overpresented in contrast to the whole group. This may indicate an influence of the choosen approach and that for the position of the tumor to the change of the taste score. The observations should be verified on a greater collective.

17ß-Estradiol reduces nitric oxide production in the Guinea pig cochlea.

Intense noise exposure and the application of ototoxic substances result in increased levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS), such as nitric oxide (NO). In order to reduce the free NO concentration in the inner ear under pathological conditions, the use of natural cytoprotective substances such as 17ß-estradiol is a promising therapeutic concept. In male guinea pigs the organ of Corti and the lateral wall were isolated from the cochlea and afterwards incubated for 6 h in cell-culture medium. 17ß-Estradiol was adjusted in 2 concentrations to organ cultures of the right ears (12 animals per concentration). The left ears were used as controls. The NO production was quantified in the supernatant by chemiluminescence after incubation. Depending on the concentration, 17ß-estradiol reduced NO in the organ of Corti by 43% (p=0.015) and 46% (p=0.026), respectively. In the lateral wall, the NO concentration was reduced by 24%, but without statistical significance (p=0.86). However, when analyzing the association between the 2 cochlear regions for each animal separately, the NO concentrations were lower in nearly all 17ß-estradiol-treated ears compared to controls. In order to demonstrate the flexibility of the organ culture system, the NO donor DETA NONOate and the nitric oxide synthase inhibitors L-NAME and L-NMMA were applied. The electron microscopic analysis revealed a well-preserved cochlear cell morphology after incubation. The ability of 17ß-estradiol to influence the NO production preferentially in the organ of Corti might offer new therapeutic perspectives for inner ear protection.

Low-dose aspirin desensitization in individuals with aspirin-exacerbated respiratory disease.

BACKGROUND: Nasal polyposis frequently occurs within the clinical picture of aspirin-exacerbated respiratory disease (AERD). A derailed arachidonic acid metabolism is regarded to be part of the pathophysiology of AERD, and aspirin desensitization is the only causal therapeutic option, so far. The optimal maintenance dose of aspirin desensitization to prevent nasal polyp recurrence on the one hand and to minimize aspirin-related side-effects, on the other hand, is still a matter of debate. The aim of this trial was to investigate the efficacy and safety of a low-dose aspirin desensitization protocol. METHODS: After sinus surgery, 70 individuals with AERD were randomly allocated to a prospective double-blind placebo-controlled aspirin desensitization protocol with a maintenance dose of 100 mg daily. The primary outcome was polyp relapse after 36 months. Nasal endoscopy status, quality of life, and patients' symptom score as well as aspirin-related side-effects were monitored. RESULTS: Due to the high dropout rate, only 31 individuals were evaluated. After 36 months, nasal polyp relapse was less frequent (P = 0.0785) and the polyposis score was lower (P = 0.0702) in the therapy group. Quality of life obviously improved (P = 0.0324), clinical complaints (P = 0.0083) were significantly reduced, and no severe aspirin-related side-effects were observed. CONCLUSION: Aspirin desensitization with a maintenance dose of 100 mg daily has a positive impact on nasal polyp relapse and seems to be a safe and suitable therapy to improve clinical complaints and the quality of life of individuals with AERD.

Comparison of subjective olfaction ratings in patients with and without olfactory disorders.

OBJECTIVE: Olfactory dysfunction is common. The reliability of self-assessment tools for smell testing is still controversial. This study aimed to provide new data about the accuracy of olfactory self-assessment compared with a standardised smell test. DESIGN: Prospective, controlled, cohort study of patients with olfactory disorders and healthy controls. SUBJECTS: Ninety-six patients with a smell deficit and 71 controls were asked to rate their sense of smell on a visual analogue scale. Their olfactory abilities were also evaluated with the Sniffin' Sticks tests. RESULTS: The whole cohort showed a significant correlation between visual analogue scale smell scores and Sniffin' Sticks total scores. This correlation was also significant in the patient group, but not in the control group. These results were independent of olfactory deficit aetiology and subject age. CONCLUSION: Self-assessment of olfaction is only a reliable indicator in smell-impaired patients, not in healthy controls. For an accurate assessment of olfaction, reliable, standardised tests are needed.

Lack of neurofibromatosis type 2 gene promoter methylation in sporadic vestibular schwannomas.

BACKGROUND: Vestibular schwannomas (VS) are benign tumors of the nervous system that are usually sporadic but also occur in the inherited disorder neurofibromatosis type 2 (NF2). In VS, losses of chromosomal material and mutations of the NF2 gene have been established to be causative. For a subset of VS without detectable gene alterations, promoter inactivation by hypermethylation has been suggested. However, published data are very limited and contradictory. METHODS: We analyzed NF2 gene promoter methylation in 35 sporadic VS by methylation-specific PCR. RESULTS: Twenty-three of the tumors were informative, showing no promoter methylation. In the remaining 12 tumors, promoter methylation could neither be verified nor excluded. CONCLUSIONS: Our study suggests that NF2 gene inactivation by promoter hypermethylation is a rare or very uncommon mechanism of NF2 gene inactivation in sporadic VS. Other mechanisms destabilizing the NF2 gene product, yet to be identified, might play a role in the genesis of VS apart from the loss or mutation of the NF2 gene.

[Subglottic tracheal stenosis]. / Subglottische Trachealstenosen.

OBJECTIVES: To assess the results of endoscopic CO(2) laser resections combined with mitomycin-C and/or triamcinolone acetonide therapy in the treatment of patients with symptomatic subglottic tracheal stenosis. MATERIALS AND METHODS: Eleven patients (all female) with subglottic tracheal stenosis were divided into two groups: six patients with idiopathic subglottic tracheal stenosis and five with subglottic tracheal stenosis of known etiology (four with Wegener's disease and one with polychondritis of the trachea). Three patients showed signs of reflux. The primary outcome measure was improvement of the clinical symptoms and the secondary the postoperative reduction of airway resistance. RESULTS: All patients were treated with CO(2) laser resections combined with mitomycin-C and/or triamcinolone acetonide therapy. Postoperative examinations during a period of 7 to 72 months demonstrated a reduction of symptoms and of airway resistance in all patients. CONCLUSIONS: One or more endoscopic CO(2) laser resections combined with mitomycin-C and/or triamcinolone acetonide therapy are effective in the treatment of subglottic tracheal stenoses. Long-term oral steroid and immunosuppressive therapy as well as the use of proton pump inhibitors positively influences the postoperative outcome.

[Deficits in medical counseling in olfactory dysfunction]. / Defizite der ärztlichen Beratung bei Riechstörungen.

Olfactory dysfunctions are common with a prevalence of up to 20% in the population. An impaired sense of smell can lead to specific dangers, therefore, counseling and warning of hazardous situations to raise patient awareness is an important medical function. In this study 105 patients presenting to the University of Mainz Medical Centre with dysosmia were evaluated using a questionnaire. For quantification of the olfactory dysfunction a standardized olfactory test (Sniffin' Sticks) was used. Of the patients 46% were hyposmic and 40% were functionally anosmic. The median duration of the olfactory impairment was 10 months and the main causes of dysosmia were upper respiratory tract infections and idiopathic disorders. More than 90% of the patients consulted an otorhinolaryngologist and 60% a general practitioner before presenting to the University of Mainz Medical Center. More than two thirds of the patients conducted a professional activity, 95% of patients reported that they had not received any medical counseling and 6% of the subjects were forced to discontinue their profession because of olfactory dysfunction. In patients with olfactory dysfunctions appropriate diagnostics, including olfactometry should be performed. Furthermore, correct medical counseling concerning necessary additional arrangements (e.g. installation of smoke or gas detectors, precautions while cooking or for hygiene) has to be performed. For patients in a profession an analysis of the hazards at work is crucial.

The VEGF/VEGF-R axis in sporadic vestibular schwannomas correlates with irradiation and disease recurrence.

BACKGROUND/AIMS: The molecular mechanisms downstream of mutated neurofibromatosis type 2 (NF2) gene resulting in the growth and development of vestibular schwannoma (VS) are controversial. Several lines of evidence suggest the involvement of the vascular endothelial growth factor (VEGF) pathway in VS development. Given that recent studies of VEGF blockade in patients with NF2-associated VS showed positive effects on VS growth control, we initiated this comprehensive study of the VEGF pathway in sporadic VS. METHODS: A tissue microarray analysis of 182 sporadic VS was conducted. The expression of VEGF and its receptors as well as the proliferative activity of the tumors were quantified. The expression data were correlated to tumor volumes and diameters as well as to tumor recurrence and previous irradiation. RESULTS: All studied tumors expressed VEGF and its receptors. Proliferative activity was related to the growth characteristics of the tumors. Moreover, we found significantly higher VEGF levels in recurrent tumors (p = 0.0387) and in preoperatively irradiated tumors (p = 0.0213). CONCLUSION: Our data suggest a relevant role of the VEGF pathway in VS growth and therapy outcome. Therefore, targeting this pathway using antiangiogenic compounds might be beneficial for patients with sporadic VS, especially those with recurrent or irradiated tumors.

[Possible molecular mechanisms of spontaneous remission in sudden idiopathic hearing loss]. / Mögliche molekulare Mechanismen einer Spontanremission nach Hörsturz.

According to current knowledge, it must be assumed that temporary idiopathic hearing loss and its spontaneous remission are based on mechanical and/or pathological alterations in the inner ear. The causal mechanisms might be based on inter-individual variations. Induced by dose-dependent activators, temporary as well as permanent damage might occur. Sudden hearing loss may be initiated by an increase in the local nitric oxide (NO) concentration. Spontaneous remission, i.e. functional restoration, can be explained by a local decrease in the NO concentration. In this context, regulatory systems such as the gap-junction system, blood vessels or synapses might be affected. In addition, alterations in the hormone level of estrogen and mineralocorticoids, as well as cellular glutathione and vitamin levels, might lead to temporary alterations in the inner ear. Recent experimental findings indicate a role for the shuttle protein Survivin in the spontaneous remission of sudden hearing loss.

No evidence for a correlation of glutathione S-tranferase polymorphisms and chronic rhinosinusitis.

OBJECTIVE: Cellular detoxification mechanisms are mandatory for cellular protection against oxidative stress and reactive oxygen species. One major group of antioxidative active enzymes involved in cellular detoxification are the Glutathione S-Transferases (GST). Multiple subtypes like GSTM1, GSTP1, and GSTT1 and variants of them are known, arising from allelic variations of the GST loci. Moreover, functional variants occur in high percentages and have been associated with diseases like bronchial asthma and bronchial hyperresponsiveness. The interplay of oxidative stress, detoxifying genes like GSTs and the genesis of respiratory tract illness is under contradictory debate. In this study, we analysed the potential association of GST-polymorphisms and chronic rhinosinusitis (CRS). METHODS: In total 170 nasal tissue samples, 49 tissue samples from patients with CRS without nasal polyps, 69 tissue samples from CRS with nasal polyps and 52 healthy tissue controls of the inferior turbinate were analysed for their individual GST-status. Genotypes for GSTM1 (null versus present), GSTT1 (null versus present), and GSTP1 (Ile105Val) were determined by Polymerase Chain Reaction. The respective genotypes were correlated to the incidence of CRS with and without nasal polyps in aspirin-tolerant and intolerant patients and to the individual health status concerning asthma and allergies. RESULTS: No correlation between any GST-polymorphism and CRS with and without nasal polyps or allergies or asthma or aspirin-intolerance was observed. CONCLUSION: Our results do not suggest that there is a relevant genetic predisposition considering the individual GST-status for the susceptibility of nasal respiratory epithelia leading to CRS.

Genomic changes in salivary gland pleomorphic adenomas detected by comparative genomic hybridization.

The aim of this study was to investigate whether so far unknown chromosomal alterations in pleomorphic adenoma (PA) exist. To this end, tissue samples from 18 patients with parotid gland PA were studied by comparative genomic hybridization (CGH) using Phi-29-DNA-polymerase for DNA amplification. The most common aberrations were losses of chromosomal material of 19p (6/18), 9q, 16p, and 19q (in 3 out of 18 patients each). Additional losses were observed on 4p, 5q, and 17q (2 / 18 each). Gains involved chromosomes 2p, 4p, 6p, 17q, and 21q (2 / 18 each). Losses of 19p have been associated with inactivation of tumor-suppressor genes in carcinomas previously. As a result, pleomorphic adenomas show a considerable diversity of chromosomal gains and losses detected by CGH. The 19p arm, and particularly its 19p13 region, need be further studied to elucidate the potential impact of associated lost tumor suppressor genes on PA development.

Evaluation of the efficacy of the 'nasal airflow-inducing manoeuvre' for smell rehabilitation in laryngectomees by means of the Sniffin' Sticks test.

OBJECTIVE: To determine the efficacy of the nasal airflow-inducing manoeuvre (NAIM) as a method for olfactory rehabilitation in laryngectomees by the means of the Sniffin' Sticks test. STUDY DESIGN: Prospective open interventional trial. SETTING: Tertiary academic hospital. PARTICIPANTS: Thirty-seven patients after laryngectomy have been screened and 25 patients have been included into the study. The participant's sense of smell was tested with the Sniffin' Sticks test before and after learning the nasal airflow inducing manoeuvre. The individual level of threshold, discrimination and identification (TDI) was determined and the individual threshold, discrimination and identification score was used to classify the patients as being anosmic, hyposmic or normosmic. MAIN OUTCOME MEASURES: The primary endpoint was the change of the threshold, discrimination and identification score before and after learning the nasal airflow inducing manoeuvre. The secondary endpoint was a change in the diagnostic group (normosmic, hyposmic and anosmic) after learning of the nasal airflow inducing manoeuvre. RESULTS: There was a statistically significant increase in the total threshold, discrimination and identification score (P < 0.001) and the three sub-scores (P ≤ 0.02) before and after the learning of the nasal airflow inducing manoeuvre. Patients gained seven points on average in the threshold, discrimination and identification score. Twenty of 25 patients showed an increase of five or more point in the threshold, discrimination and identification score. In the classification of the smell ability, 15 of 25 patients showed a change to a higher class (hyposmic to normosmic or from anosmic to hyposmic or normosmic). CONCLUSION: The nasal airflow inducing manoeuvre is a method for the successful rehabilitation of the sense of smell in laryngectomees. The evaluation with the Sniffin' Sticks tests showed a clinically relevant increase of olfaction in 80% of patients. The teaching of the nasal airflow inducing manoeuvre should be included in post-laryngectomy rehabilitation programmes.

An otoprotective role for the apoptosis inhibitor protein survivin.

Hearing impairment caused by ototoxic insults, such as noise or gentamicin is a worldwide health problem. As the molecular circuitries involved are not yet resolved, current otoprotective therapies are rather empirical than rational. Here, immunohistochemistry and western blotting showed that the cytoprotective protein survivin is expressed in the human and guinea pig cochlea. In the guinea pig model, moderate noise exposure causing only a temporary hearing impairment transiently evoked survivin expression in the spiral ligament, nerve fibers and the organ of Corti. Mechanistically, survivin upregulation may involve nitric oxide (NO)-induced Akt signaling, as enhanced expression of the endothelial NO synthase and phosphorylated Akt were detectable in some surviving-positive cell types. In contrast, intratympanic gentamicin injection inducing cell damage and permanent hearing loss correlated with attenuated survivin levels in the cochlea. Subsequently, the protective activity of the human and the guinea pig survivin orthologs against the ototoxin gentamicin was demonstrated by ectopic overexpression and RNAi-mediated depletion studies in auditory cells in vitro. These data suggest that survivin represents an innate cytoprotective resistor against stress conditions in the auditory system. The pharmacogenetic modulation of survivin may thus provide the conceptual basis for the rational design of novel therapeutic otoprotective strategies.

[Management of Graves' orbitopathy: evidence-based recommendations]. / Vorgehen bei endokriner Orbitopathie. Evidenzbasierte Empfehlungen.

Patients with Graves' orbitopathy (GO) suffer from disfiguring proptosis, orbital pain and diplopia. Compression of the optic nerve may cause functional restrictions to the point of loss of vision. Since suboptimal management of GO seems to be widespread, the European Group On Graves' Orbitopathy (EUGOGO) provided a consensus statement on the management of GO. According to EUGOGO, patients with GO should be referred to multidisciplinary specialist centers. All patients should be encouraged to quit smoking. Prompt treatment of thyroid dysfunction is mandatory in order to restore and maintain euthyroidism. The first-line treatment for optic neuropathy and/or corneal ulceration are intravenous glucocorticoids. If the response is poor after 1-2 weeks, orbital decompression surgery should follow. Intravenous glucocorticoids are also recommended in patients with moderate-to-severe and active GO. If GO is inactive, surgery should be considered. Local measures and an expectant strategy are sufficient in most patients with mild GO, but if quality of life is affected significantly, specific treatment may be justified. Thus, management of GO remains challenging and is best performed within a multidisciplinary orbital center.

[Malignant thyroid neoplasms: a diagnostic challenge for ENT specialists]. / Das Schilddrüsenmalignom: Eine diagnostische Herausforderung für den HNO-Arzt.

BACKGROUND: Thyroid carcinoma is frequently diagnosed incidentally during routine ENT examinations. METHODS: Symptoms and clinical findings of 40 patients with thyroid malignancies presenting in our department were analysed retrospectively. The aim was to define characteristics indicative for the final diagnosis of thyroid malignancy. RESULTS: In 48% the initial presentation was not because of thyroid-specific complaints, however during the course of the general ENT examination, unspecific thyroid pathology was detected and further evaluated using sonography, scintigraphy and fine needle biopsy (FNB). The results of scintigraphy were suspicious in 67% and FNB was positive in 30%, inconclusive in 30% and false negative in 40%. For suspected malignancies a rapid frozen section examination was carried out which was positive only in 60% and false negative or inconclusive in 20% each. CONCLUSION: Thyroid lesions incidentally found during ENT examination should undergo ultrasound examination, FNB and scintigraphy with the clear understanding that there is no single diagnostic feature leading to the correct diagnosis and that only the synopsis of various findings and sometimes only final histology leads to the correct diagnosis.

[Protection of the cochlea by ascorbic acid in noise trauma]. / Protektion der Kochlea durch Vitamin C bei Lärmexposition.

BACKGROUND: The protective effect of ascorbic acid against noise-induced hearing loss and increased nitric oxide (NO) formation after noise exposure have already been demonstrated in animal models. However, the influence of ascorbic acid on noise-induced NO production within the cochlea is still unclear. METHODS: Guinea pigs (n=48) were fed for 7 days with low [25 mg/kg bodyweight (bw)/day] and high (525 mg/kg bw/day) doses of ascorbic acid. Then half of the animals were exposed to noise (90 dB for 1 h). The hearing levels were recorded beforehand, on the 3rd and 7th days after feeding, and directly after noise exposure. Finally, the organ of Corti and the lateral wall were removed from the inner ear and incubated separately for 6 h in culture medium, and the nitrite content was determined in the supernatant. RESULTS: Compared with low-dose feeding, feeding of high doses of ascorbic acid resulted in a reduction of hearing impairment of about 8 dB after noise exposure. A correlation between hearing improvement and decreased NO production was detectable for both cochlea regions but was more pronounced in the lateral wall. CONCLUSION: A high dose of ascorbic acid lowers NO production in the inner ear, reduces hearing loss, and protects the cochlea from nitroactive stress.

[Tonsillotomy with bipolar coagulation scissors]. / Die Tonsillotomie mit der bipolaren Koagulationsschere.

BACKGROUND: Nowadays, tonsillotomy is an accepted operating procedure for the diagnosis of tonsillar hyperplasia in small children. Up to now many different techniques such as laser, radiofrequency, coblation or micro-debrider have been used. In this study, for the first time bipolar coagulation scissors were utilized. METHODS: Up to December 2006, a total of 91 children with benign tonsillar hyperplasia were tonsillotomized by bipolar coagulation scissors. Of these 91 children, 38 (average age 74 months) were recruited for this study. Pre-operative and post-operative complaints were documented and the success of the operation was evaluated by the parents. RESULTS: In more than 90 % of the children, pre-operative complaints had disappeared completely after surgery. The operation was considered by all parents to have been very helpful. With no child did re-tonsillotomy or tonsillectomy have to be performed in the observation interval, which was a maximum of three years. CONCLUSION: Tonsillotomy with the bipolar coagulation scissors is a reliable method of surgery in children with tonsillar hypertrophy. This type of scissors offers an ideal combination of dissection and coagulation. From an economic point of view, the bipolar coagulation scissors offer a clear advantage over laser.

[No correlation between reflux of gastric contents and obstructive sleep apnea]. / Besteht ein Zusammenhang zwischen der Refluxerkrankung und dem obstruktiven Schlafapnoesyndrom?

Reflux of gastric contents can be associated with many ENT disorders. Some authors describe an association with obstructive sleep apnea, but it is not clear whether the reflux causes the apnea or vice versa. Furthermore, authors did not distinguish between gastroesophageal reflux and extraesophageal reflux, which is essential to understand a connection with obstructive sleep apnea. Therefore, we performed polysomnography and two-channel pH testing simultaneously in patients with obstructive sleep apnea syndrome (OSAS) and compared the findings with data of healthy volunteers. After exclusion of a changed sleep architecture due to the pH testing system, the results show that patients with OSAS do not suffer more often from reflux than healthy volunteers. This is true for gastroesophageal as well as for extraesophageal reflux. Furthermore, an increasing number of reflux events during the night is not correlated with the number of apnea events. Thus, in summary our data cannot support the postulation that there is a connection between obstructive sleep apnea syndrome and reflux disease.

Multifocal adult rhabdomyoma of the head and neck: a case report and literature review.

Adult rhabdomyoma is a rare, usually solitary, primary tumour of striated muscle origin that almost exclusively presents in the head and neck region with predilection for male. We herein present a rare case of a multifocal adult rhabdomyoma in a 72-year-old woman. The lesions were located, the first one in the area of the left aryepiglottic fold and the second one right cervical arising from oesophagus. The diagnosis of the cervical mass was obtained prior to resection through cytological examination (FNAC). We discuss the clinical, cytological and histological findings and we provide a brief review of the literature on this entity.

[Determination of normal values of extraesophageal reflux in 24-h two-channel pH testing]. / Normalwertbestimmung des extraösophagealen Reflux (EER) in der 24-h-2-Kanal-pH-Metrie.

Extraesophageal reflux (EER) causes multiple diseases of the upper aerodigestive tract. EER is diagnosed by two-channel pH testing. However, little data exist about normal values. Therefore, we performed ambulatory two-channel pH testing in healthy volunteers and determined normal values for the number of reflux episodes, fraction, and reflux area index. These values were determined for pH 14.72 were excluded from the evaluation. In the other patients, the mean number of reflux episodes was 2.6+/-0.9 (95(th) percentile 4.4), the fraction of pH