Tinnitus and mobile phone use.

OBJECTIVES: The mechanisms that produce tinnitus are not fully understood. While tinnitus can be associated with diseases and disorders of the ear, retrocochlear diseases and vascular pathologies, there are few known risk factors for tinnitus apart from these conditions. There is anecdotal evidence of an link between mobile phone use and tinnitus, but so far there have been no systematic investigations into this possible association. METHODS: 100 consecutive patients presenting with tinnitus were enrolled in an individually matched case-control study. For each case a control subject was randomly selected from visiting outpatients matched for sex and age. The patient's history was obtained and clinical examinations were conducted to exclude patients with known underlying causes of tinnitus. Mobile phone use was assessed based on the Interphone Study protocol. ORs were computed by conditional logistic regression with years of education and living in an urban area as covariates. RESULTS: Mobile phone use up to the index date (onset of tinnitus) on the same side as the tinnitus did not have significantly elevated ORs for regular use and intensity or for cumulative hours of use. The risk estimate was significantly elevated for prolonged use (≥4 years) of a mobile phone (OR 1.95; CI 1.00 to 3.80). CONCLUSIONS: Mobile phone use should be included in future investigations as a potential risk factor for developing tinnitus.

Analysis of 60 patients after tympanotomy and sealing of the round window membrane after acute unilateral sensorineural hearing loss.

OBJECTIVE: This retrospective study was performed to evaluate the effectiveness of tympanotomy and sealing of the round window membrane after unilateral acute hearing loss. DESIGN: All patients presenting idiopathic sudden hearing loss, acoustic, or barotrauma were treated with prednisolone and caroverine. Thirty-six patients had a mean pure tone hearing level worse than 70 dB. Recovery was defined as improvement of hearing threshold for 5 frequencies (250, 500, 1000, 2000, and 4000 Hz). If hearing did not improve after conservative treatment, an exploratory tympanotomy and sealing of the round window membrane were suggested. In the last 8 years, 60 patients with idiopathic sudden hearing loss, acoustic, or barotrauma underwent tympanotomy. RESULTS: In 40 patients, we observed improvement of hearing level up to complete remission. In 20 patients, no change could be detected. In the group of patients with documented barotrauma, 12 patients showed improved hearing levels. Of 37 patients with idiopathic sudden hearing loss, 26 had an improved hearing after surgery. Most patients were operated on within 14 days (range, 1-60 days), but time of surgery had no influence on outcome in patients with idiopathic hearing loss. In contrast, in patients with barotrauma, time of surgery seems to have an influence on outcome. CONCLUSIONS: Tympanotomy and sealing of the round window membrane can be recommended in cases of acute hearing loss after failure of conservative treatment.

Improved postural control after computerized optokinetic therapy based on stochastic visual stimulation in patients with vestibular dysfunction.

Balance is accomplished by the congruent integration of visual, vestibular and somatosensory input and the execution of adequate control movements. With increasing age, nonlinear dynamics of central control systems become more regular. In unilateral vestibular dysfunction, sensory input to central systems is similarly less complex, because of one sided reduction of information influx. This study aimed to increase postural stability in patients with vestibular asymmetry and resulting disequilibrium by implementing a computerized visual training method relying on the principles of stochastic resonance. 24 subjects (average age 64a, 31-78a, 15 women, 9 men), with minimum 3 months of persisting disequilibrium due to vestibular dysfunction, were either treated with computerized optokinetic therapy (COKT), or solely observed. Treated patients were requested to read texts, stochastically moving in a previously defined matrix, during 10 sessions over three weeks. The Sensory Organization Test (SOT) was used for comparative posturographic measurements. COKT patients showed significant improvement in conditions 4, 6 and composite score. A significant post-therapeutic difference was seen between therapy and control groups in conditions 1, 6 and composite score. The results show a clinical benefit and we conclude COKT to be an effective rehabilitation method in patients with chronic disequilibrium.

Topical administration of Caroverine in somatic tinnitus treatment: proof-of-concept study.

This prospective study, which conformed with good clinical practice (GCP-conform), tested the concept that the topical transtympanic administration of the quinoxaline derivative Caroverine promises a new approach to the treatment of tinnitus. The rationale for the study is the hypothesis that tinnitus reflects sequelae of auditory neurotoxicity that can prevented and repaired by the neuroprotective and neuroregenerative activities of quinoxaline derivatives exhibited in previous preclinical tests. In a representative patient cohort, the probability of a long-lasting tinnitolytic effect of lipophilic eardrops containing 1% Caroverine as their active ingredient gained in significance, crossing from low-intensity levels to high-intensity levels of individual tinnitus sensations. These results encouraged us to design consequential GCP-conform phase 2 and phase 3 studies.

The antioxidant activity of caroverine.

Caroverine, 1-(2-diethylaminoethyl)-3-(p-methoxy benzyl)-1,2-dihydro-2-quinoxalin-2-on-hydrochloride, is a class B calcium-channel-blocker and antiglutamatergic agent with significant effects on the brain function. Caroverine exhibits competitive AMPA antagonism, and at higher concentrations, noncompetitive NMDA antagonism. In clinical practice caroverine is used as a spasmolytic and otoneuroprotective agent. Since reactive oxygen species are supposed to be involved in the pathogenesis of inner ear diseases in which caroverine shows beneficial effects, the present study aimed to investigate the antioxidant properties of caroverine. Lipid peroxidation of liposomal membranes was suppressed in the presence of caroverine. In order to understand the mechanism of this antioxidant action of caroverine, we determined the rate constants both for a possible reaction with superoxide (O(2)(.-)) radicals from xanthine/xanthine oxidase and for a possible reaction with hydroxyl (.OH) radicals in Fenton system. Using a defined chemical reaction model O(2)(.-) scavenging was found to occur at a rather low rate constant only (3 x 10(2)M(-1)s(-1)). Thus, a reaction of caroverine with O(2)(.-) radicals is of marginal significance. In contrast, the reaction of caroverine with .OH radicals occurs at an extremely high rate constant (k=1.9 x 10(10)M(-1)s(-1)). The strong antioxidant activity of caroverine is therefore based both on the partial prevention and highly active scavenging of hydroxyl radicals.

Do middle ear muscles trigger attacks of Menière's disease?

OBJECTIVE: Current surgical methods for treating Ménière's disease (MD), e.g. endolymphatic sac surgery, mastoidectomy or insertion of middle ear ventilation tubes, only improve vertigo and fail to influence the hearing threshold. In this retrospective study we examined the long-term effects of tenotomy on the symptoms of MD. MATERIAL AND METHODS: A total of 45 patients suffering from definite MD underwent middle ear muscle tenotomy, a treatment that is very rarely considered nowadays. Of these 45 patients, 20 were observed postoperatively for a period of > 2 years. The disease was scored pre- and postoperatively and the results were evaluated according to the American Academy of Otolaryngology-Head and Neck Surgery Committee on Hearing and Equilibrium guidelines for the diagnosis and evaluation of therapy for MD. RESULTS: Sectioning of the tensor tympani and stapedius muscle tendons significantly reduced the frequency and intensity of vertigo and improved both the functional profile and tinnitus. Pure-tone audiometry at frequencies between 500 and 3000 Hz substantiated the improvement in hearing threshold, as did the pure-tone average. The therapeutical outcome was stable in cases where both tendons remained persistently disconnected. Intratympanal inflammatory reactions were observed in most patients during surgery. CONCLUSION: Our results prove that tenotomy is a successful and enduring therapeutic approach for treating the auditory and vestibular symptoms of MD and strongly suggest that it should be reconsidered as a promising surgical treatment for the symptoms of MD.

The quinoxaline derivative caroverine in the treatment of sensorineural smell disorders: a proof-of-concept study.

The treatment of non-conductive olfactory disorders is to a large extent an unsolved problem. This proof-of-concept study focused on possible effects of the N-methyl-D-aspartate (NMDA) antagonist caroverine. Potential mechanisms for the hypothesized effect included reduced feedback inhibition in the olfactory bulb as a consequence of NMDA antagonistic actions and antagonism of an excitotoxic action of glutamate. A total of 77 consecutive patients with non-conductive olfactory disorders were included in the study. Fifty-one patients received caroverine for 4 weeks (120 mg/day); 26 controls matched for age, gender and duration of olfactory loss were treated with zinc sulfate for the same length of time (400 mg/day). Olfactory sensitivity was evaluated before and after treatment. Testing included assessment of n-butanol odor threshold and odor identification. When compared to baseline, treatment with caroverine improved both odor thresholds (p = 0.005) and odor identification (p = 0.042) in anosmic patients. In hyposmic patients it significantly improved odor identification ability (p = 0.041). In contrast, zinc sulfate had no significant effect on olfactory function. These results indicate that caroverine appears to be effective for the treatment of non-conductive smell disorders.

7beta-hydroxycholesterol induces apoptosis and regulates cyclooxygenase 2 in head and neck squamous cell carcinoma.

OBJECTIVE: To determine whether treatment with 7beta-hydroxycholesterol (7beta-HC) would trigger cell death in head and neck squamous cell carcinoma (HNSCC) cell lines in a dose-dependent fashion. DESIGN: In vitro study. SUBJECTS: The study included HNSCC cell lines SCC9, SCC25, CAL27, and FaDu. INTERVENTION: We treated HNSCC cell lines with increasing doses of 7beta-HC. Proliferation assays were performed to assess cell viability after treatment. Western blots were carried out to evaluate cyclooxygenase (COX)-1 and -2 expression levels. RESULTS: Using proliferation assays and immunocytochemical analysis, we detected significant growth inhibition via apoptosis in 4 different HNSCC cell lines after treatment with 7beta-HC (P < .001). The 50% inhibitory concentration levels were between 13.19 and 20.79 micromol/L after 72 hours. Western analysis indicated that COX-2, but not COX-1, levels were suppressed after treatment. CONCLUSIONS: Treatment with 7beta-HC resulted in suppression of HNSCC growth in vitro. Our data warrant further investigations for the potential use of 7beta-HC as a cytotoxic agent in head and neck cancer.

Multiple aspects related to self-awareness and the awareness of others: an electroencephalography study.

The effect of possessive pronouns on the encoding of pronoun-noun associations (e.g., my garden) was investigated using the electroencephalography (EEG). Following an alphabetical, semantic and a contextual encoding instruction depth of noun processing was varied within three separate experiments in order to manipulate the grade of awareness related to verbal information processing. Only for the semantic encoding task (lexical decision) response time was significantly longer for nouns associated with the pronoun "mein" (German for "my") than for nouns associated with the pronoun "ein" (German for "a") although pronouns were not to be consciously processed at all. Following recognition tests related to nouns (without their previously associated pronouns) revealed no significant differences related to the number of correctly identified repeated nouns (hits) depending on the kind of previously associated pronoun. The analysis of neurophysiological data revealed a time range between about 250 ms and 400 ms after stimulus onset within which significant pronoun x electrode interactions occurred. No interaction with depth of word processing was found. Overlaid EEG curves, t maps and low resolution brain electromagnetic tomography (LORETA) demonstrate that in this time range "mein" and "sein" associated conditions elicit similar brain activity, both more negative, compared to the "ein" associated condition over occipital electrodes. On the other hand, at left temporal sites the "mein" condition elicited more negative potentials than both other conditions. It is interpreted that EEG recordings reveal two relevant areas, which are sensitive to the concept of a person (as represented by a personal pronoun) between about 250 ms and 400 ms after stimulus onset. One area is located in the occipital region and can distinguish between personal engagement and a neutral condition and the other area is located in the temporal region and is able to distinguish between oneself and somebody else. Together with our previous MEG results (Walla et al. in Neuropsychologia 45:796-809, 2007) we want to combine the inferences in the frame of the "multiple aspects" hypothesis related to research on self-awareness and the awareness of others.

Clinical experience with caroverine in inner ear diseases.

The glutamatergic synapses between the cochlear inner hair cells and their afferent neurons seem to be mostly involved in the pathophysiology of the cochlea. Glutamatergic neurotoxicity is characterized by a mitochondrial overproduction of free oxygen radicals damaging lipid membranes and DNA structures of the postsynaptic neuron followed by the clinical symptoms of hearing loss and tinnitus. In preclinical tests, quinoxaline derivatives antagonized these deleterious consequences of too high an amount of free radicals. Therefore the clinically available quinoxaline dione caroverine provides a new approach to a successful treatment of tinnitus, sudden hearing loss and speech discrimination disorders in presbyacusis. The results of corresponding clinical trials are presented.

Different action of memantine and caroverine on glutamatergic transmission in the mammalian cochlea.

Glutamate is the major transmitter candidate between inner hair cells and the afferent neurons of the mammalian cochlea. We investigated the action of memantine (1-amino-3,5-dimethyl-adamantane) and the quinoxaline derivative caroverine [1-diethylaminoethyl-3,8-(p-methoxybenzyl)-1,2-dihydro-quinoxaline-dione] on the glutamatergic transmission in the guinea pig cochlea utilizing extracellular recording techniques and microiontophoretic ejection of substances. While memantine was able to inhibit the NMDA (N-methyl-D-aspartate)-induced firing, the AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid)-stimulated activity was unaffected. In contrast, caroverine could block both NMDA- as well as AMPA-induced firing. As memantine and caroverine are currently in clinical use, these substances could be introduced to the treatment of several cochlear disorders.

Change of complexity patterns in human posture during aging.

Human posture is a prototypical example of a complex control system. The joint output of several physiological - most likely nonlinearly interacting - processes leads to correctional movements which enable us to stand upright. These correctional body movements reflect some features of the underlying control mechanisms. We analyze the movements of quietly standing persons by means of various types of fractal measures, which are designed to capture 'degrees of complexity'. We observe changes of these fractal measures as a function of age and show that aging goes hand in hand with a decrease of complexity in movement patterns towards more regular movements. We try to explain these results in a stochastic resonance framework. We conjecture that the reduction of posture complexity is linked to deteriorated balance performance and argue that clinical treatment of age-related balance problems should focus on regaining this complexity therapeutically. We line out two possible starting points for actual therapy.