[Multicenter trial for sudden hearing loss therapy - planning and concept]. / Multizentrische Studie zur Hörsturztherapie - Planung und Konzeption.

Systemic steroids are widely used worldwide as a standard of care for primary therapy of idiopathic sudden sensorineural hearing loss (ISSHL). The German ISSHL guideline recommends high-dose steroids for primary therapy of ISSHL, without evidence from randomized controlled trials (RCTs). The rationale for the treatment of ISSHL using high dose steroids is only based on retrospective cohort studies.This article describes the planning and initiation of a multicenter, national, randomized, controlled clinical trial entitled Efficacy and safety of high dose glucocorticosteroid treatment for idiopathic sudden sensorineural hearing loss - a three-armed, randomized, triple-blind, multicenter trial (HODOKORT). This clinical trial aims to compare standard dose with two types of high-dose steroids for primary systemic therapy with respect to their efficacy in improving hearing, and thus communication ability, in patients with idiopathic sudden sensorineural hearing loss.This study is funded by the "Clinical Trials with High Patient Relevance" research program in the health research framework of the German Federal Ministry of Education and Research. It is one of two studies by the German Study Center of Clinical Trials of the German Society of Otorhinolaryngology, Head and Neck Surgery (DSZ-HNO). Planning and initiation was done in cooperation with the DSZ-HNO, the Coordination Center of Clinical Trials of the Martin-Luther-University Halle-Wittenberg, and the Study Center of the University Hospital Freiburg.

Nonlinear amplification of side-modes in frequency combs.

We investigate how suppressed modes in frequency combs are modified upon frequency doubling and self-phase modulation. We find, both experimentally and by using a simplified model, that these side-modes are amplified relative to the principal comb modes. Whereas frequency doubling increases their relative strength by 6 dB, the growth due to self-phase modulation can be much stronger and generally increases with nonlinear propagation length. Upper limits for this effect are derived in this work. This behavior has implications for high-precision calibration of spectrographs with frequency combs used for example in astronomy. For this application, Fabry-Pérot filter cavities are used to increase the mode spacing to exceed the resolution of the spectrograph. Frequency conversion and/or spectral broadening after non-perfect filtering reamplify the suppressed modes, which can lead to calibration errors.

[Bilateral deafness due to labyrinthitis in a patient with Crohn's disease]. / Beidseitige Ertaubung durch Labyrinthitis bei M. Crohn.

Labyrinthitis with vestibulocochlear dysfunction in chronic inflammatory bowl disease is a rare but well described manifestation or complication. The diagnostic and therapeutic possibilities and limitations of this inflammatory otopathy are presented and discussed in the context of a case report. A bilateral loss of vestibular function and sensorineural hearing loss occurred in a 26-year-old male patient with previously diagnosed Crohn's disease. He was treated with immune suppressive therapy during the onset and development of cochleovestibular symptoms. Diagnostic tests included pure tone audiograms, speech audiometry, caloric tests, VEMPs, and MRI. Therapy included azathioprine, corticosteroids (systemic and intratympanic), monoclonal antibodies, and cochlear implants. Despite immunosuppressive therapy including monoclonal antibodies, the patient progressively lost his hearing. Finally, bilateral cochlear implantation was carried out with good results. The treatment of patients with systemic inflammatory or autoimmune disease affecting the cochlear-vestibular organ is challenging. An interdisciplinary approach is needed. In cases of bilateral deafness, cochlear implantation is a satisfactory treatment and should not be delayed unnecessarily.

14 GHz visible supercontinuum generation: calibration sources for astronomical spectrographs.

We report the use of a specially designed tapered photonic crystal fiber to produce a broadband optical spectrum covering the visible spectral range. The pump source is a frequency doubled Yb fiber laser operating at a repetition rate of 14 GHz and emitting sub-5 pJ pulses. We experimentally determine the optimum core diameter and achieve a 235 nm broad spectrum. Numerical simulations are used to identify the underlying mechanisms and explain spectral features. The high repetition rate makes this system a promising candidate for precision calibration of astronomical spectrographs.

Planar Steering of a Single Ferrofluid Drop by Optimal Minimum Power Dynamic Feedback Control of Four Electromagnets at a Distance.

Any single permanent or electro magnet will always attract a magnetic fluid. For this reason it is difficult to precisely position and manipulate ferrofluid at a distance from magnets. We develop and experimentally demonstrate optimal (minimum electrical power) 2-dimensional manipulation of a single droplet of ferrofluid by feedback control of 4 external electromagnets. The control algorithm we have developed takes into account, and is explicitly designed for, the nonlinear (fast decay in space, quadratic in magnet strength) nature of how the magnets actuate the ferrofluid, and it also corrects for electro-magnet charging time delays. With this control, we show that dynamic actuation of electro-magnets held outside a domain can be used to position a droplet of ferrofluid to any desired location and steer it along any desired path within that domain - an example of precision control of a ferrofluid by magnets acting at a distance.

Bone conduction thresholds and skull vibration measured on the teeth during stimulation at different sites on the human head.

Vibratory auditory stimulation or bone conduction (BC) reaches the inner ear through both osseous and non-osseous structures of the head, but the contribution of the different pathways of BC is still unclear. In this study, BC thresholds in response to stimulation at several different locations including the eye were assessed, while the magnitudes of skull bone vibrations were measured on the front teeth in human subjects with either normal hearing on both sides or unilateral deafness with normal hearing on the other side. The BC thresholds with stimulation at the ipsilateral mastoid and ipsilateral temporal region were lower than the BC thresholds with stimulation at the other sites, as reported by previous works. The lower thresholds with stimulation at the ipsilateral mastoid and ipsilateral temporal region matched higher amplitudes of skull bone vibrations measured on the teeth, but only at frequencies below 1 kHz. With stimulation at the eye, the thresholds were significantly higher than those with stimulation at the bony sites in the frequency range of 0.25-4 kHz. While skull bone vibrations as measured on the teeth during stimulation at the eye were low for low frequencies, significant bone vibrations were measured at 3 and 4 kHz, indicating different pathways for BC for either the soft tissue or bony site stimulation. This finding contradicts a straightforward relationship between vibrations of the skull bones and BC hearing thresholds.

Sub-20 fs pulses shaped directly in the UV by an acousto-optic programmable dispersive filter.

Direct pulse shaping in the UV was used to compress and structure pulses throughout the range of 250 - 400 nm. Broadband pulses generated by SHG of a NOPA were used as input to an acousto-optic programmable dispersive filter. As this shaper creates lateral dispersion, aspects of Gaussian and geometric optics had to be considered for the design of the beam path. Special care was taken to produce a homogeneous input beam. We show nearly Fourier-limited pulses as short as 16.8 fs at 320 nm and 19.5 fs at 260 nm. Full control over amplitude and phase is demonstrated by generating arbitrary shapes like square pulses and complex pulse sequences. The subpulses were manipulated individually in intensity, temporal delay, chirp, relative phase and central wavelength.

Hearing loss and fluctuating hearing levels in X-linked hypophosphataemic osteomalacia.

BACKGROUND AND OBJECTIVE: X-linked hypophosphataemic osteomalacia is the most common of the genetically determined forms of osteomalacia. The occurrence of hearing loss in X-linked hypophosphataemic osteomalacia has been known since 1984. However, observations on the progression of such hearing loss, and suggestions regarding possible therapy, have not previously been published. METHODS: Case report of a patient with X-linked hypophosphataemic osteomalacia and hearing loss, with three years' audiological follow up, description of empirical therapy and literature review. RESULTS: The patient presented with fluctuating hearing. An audiogram showed mild to severe sensorineural hearing loss mainly in the low and high frequencies. A temporary improvement of 20-40 dB after steroid therapy was observed. Four weeks later, hearing had deteriorated again, mainly in the low frequencies. After one year of fluctuating hearing levels, stabilisation occurred. CONCLUSIONS: In X-linked hypophosphataemic osteomalacia, hearing loss occurs predominantly in the low and high frequencies. The hearing loss type and progression pattern point to an endolymphatic hydrops as the pathogenetic mechanism. Steroid therapy may be of some benefit.

[Universal newborn hearing screening--a silent revolution]. / Das allgemeine Neugeborenenhörscreening--eine stille Revolution.

Significant hearing loss is one of the most frequent congenital diseases and present at birth in approximately one in 1000 newborns. During the first years of life, this number of children with permanent hearing loss rises by approximately the same amount. Hearing impairment is not an obvious condition in newborns in most cases and produces very few signs in infancy. Such hearing loss threatens normal speech and personality development. The longer the child is without auditory stimulation by speech, the more difficult it is to acquire the missed linguistic skills. Therefore, early detection and rehabilitation of such hearing loss is crucial. Universal newborn hearing screening is the most effective method to detect such impairment and is based on objective audiometric test methods that were recently developed and adapted for screening requirements. Useful tests are otoacoustic emissions and the auditory brainstem response. This article reviews this new screening tests in general and with special regard to the situation in Switzerland.

Influence of artifacts and pass/refer criteria on otoacoustic emission hearing screening.

A screening device for otoacoustic emission (OAE) testing was evaluated via measurements of click evoked OAEs (CEOAEs) and/or distortion product OAEs (DPOAEs) obtained in normally hearing young adults and newborns. Moreover, measurements were performed in a passive cavity and in ears with severe sensorineural hearing loss, in which the occurrence of a pass result was assumed to indicate artifacts. Different parameter settings were investigated. In comparison to normally hearing young adults, overall pass rates in newborns were similar using CEOAEs (93 to 100%), but lower using DPOAEs (65 to 95% vs. 83 to 100%). Pass rates in ears with severe hearing loss were 10% at 2 kHz, 13% at 3 kHz, and lower at other frequencies. Pass rates in the test cavity were generally low. The influence of test frequency on pass rates and calculations using computer simulation indicated the presence of artifacts. The discrimination of such artifacts from biological signals is difficult or impossible, and they may represent a serious problem for efficient OAE screening.

Comparison of currently available devices designed for newborn hearing screening using automated auditory brainstem and/or otoacoustic emission measurements.

OBJECTIVE: Suitability in clinical practise of three currently available devices designed for automated newborn hearing screening, one combining evoked otoacoustic emissions (EOAE) and automated auditory brain stem response (AABR), the Echoscreen-TDA from Fischer-Zoth, and two AABR screeners, the Algo 3 from Natus and the Beraphone MB11 from Maico, were tested prospectively. METHODS: Transiently evoked otoacoustic emissions (TEOAE) and distortion product otoacoustic emissions (DPOAE) were measured in one ear of 150 healthy newborns using the Echoscreen-TDA. Three groups of 50 subjects each were tested additionally for AABR recordings either with Echoscreen-TDA, Algo 3 or Beraphone MB11. Measurements were performed after the second day of life. The following aspects were evaluated: (a) subject-instrumentation interface (b) test time (c) costs (unit price and costs for disposable material) and (d) pass rates. RESULTS: Connecting the subjects to the device was the easiest for EOAE measurements with the Echoscreen-TDA, followed by AABR recordings with the Algo 3 and Echoscreen-TDA and were most difficult with the Beraphone MB11. The median test time on one ear was less than 30 s for EOAE measurements and 4-5 min for AABR recordings. Costs for the equipment and for disposable material were lowest for the Echoscreen-TDA and Beraphone MB11, respectively and highest for the Algo 3. Pass rates were highest with 98% for AABR recordings using the Algo 3 and lowest with 92% for AABR recordings using the Beraphone MB11, but differences were not statistically significant. CONCLUSIONS: All tested devices can be used for universal neonatal hearing screening. It was easier to connect the subject to the device and measurements were quicker for OAE than for AABR measurements. Echoscreen-TDA combines the two techniques and had the lowest costs for the AABR equipment. Algo 3 had the highest costs for the equipment and for disposable material, but it was highly reliable, and both ears can be tested simultaneously. Connecting the subject was the most difficult with the Beraphone MB11, but there were no disposable supply costs.

[Subjective and objective audiometry]. / Subjektive und objektive Hörprüfung.

Audiometry uses physically precisely defined acoustic stimuli. The response can be either a subjective reaction of the patient such as to press a button, or it can be a physiological reaction that can be measured objectively such as the acoustic reflex of the stapedial muscle. The aims of both types of audiometry, subjective and objective, are the assessment, the localization and the quantification of hearing loss. Specifically selected subjective or objective tests, and combinations of both, are being used to answer different clinical questions related to audiometric screening, audiological diagnosis, and quantitative description of the hearing loss. The selection of tests should be designed to answer the specific question most effectively.

Relationship of intraoperative electrically evoked stapedius reflex thresholds to maximum comfortable loudness levels of children with cochlear implants.

Previous studies of the relationship between the intraoperatively obtained electrically evoked stapedius reflex threshold (ESRT) and the maximum comfortable loudness (MCL) values used to program the speech processor of cochlear implant (CI) patients have indicated that ESRTs provide an inexact estimate of MCL. In order to determine whether this estimate might be more exact for electrodes in different parts of the electrode array, we studied the electrode-specific relationships between ESRT and MCL in 29 Med-E1 Combi 40+ and 25 Nucleus CI 24 M patients after first fitting of the speech processor and 2 and 6 months later. The MCL values were mostly less than the ESRT values, but increased progressively over the first 6 months, reaching 83% and 72% of the ESRT values, on average, across all electrodes for the Med-E1 and Nucleus systems respectively. The population variation across electrodes decreased over the 6-month observation period and was least for the apical half of the array, for which the correlation coefficients of regressions between ESRT and MCL were around 0.65 for both systems. These results indicate that estimates of MCL values from the ERST are more accurate for the apical half of the intra-cochlear array and could then be described by an offset value plus an increase of MCL by 0.62 and 0.53 of ESRT for the Med-E1 and Nucleus systems, respectively.

[Partially hydrogenated aryl-1,2/1,4-anthraquinone derivatives, 5-lipoxygenase inhibitors with arotinoid structure]. / Partiell hydrierte Aryl-1,2/1,4-anthrachinon-Derivate, 5-Lipoxygenase-Inhibitoren mit Arotinoid-Struktur.

The combination of 5-LOX inhibition and retinoid activity in one molecule could be an interesting pharmacological tool to influence psoriasis. Thus we synthesized compounds with arotinoid structure by anellation of the 5-LOX inhibitors 1 and 2 with 1,1,4,4-tetramethylcyclohexane. A key step was the CuCl-MeCN-O2 oxidation of tetrahydroanthracenol 13 to the corresponding 1,2-anthraquinone 14 which could be converted to the analogous 2-hydroxy-1,4-anthraquinone 19 by Thiele-Winter reaction followed by oxidation. The halogenated quinones 9 and 21 were arylated with 2,6-di-tertbutylphenol and demethylated or hydrolyzed to the target compounds 3 and 4 which were tested in comparison with the non-anellated 5-LOX inhibitors 1 and 2 for LOX inhibition in activated human granulocytes and for antioxidative activity by the method of Popov with the chemiluminometer Photochem. The results are discussed in relation to the corresponding logP values. The 1,2-quinones 1 and 3 are more potent 5-LOX inhibitors than their 1,4-analogues 2 and 4, the tetrahydroanthraquinon derivatives 3 and 4 are less potent than the naphthoquinones 1 and 2. All compounds are devoid of any activity in cell differentiation as compared to retinoic acid as indicated by the NBT test with HL-60 leukemia cells.

Mismatch negativity and psychoacoustic measures of gap detection in normally hearing subjects.

Temporal auditory processing deficits are thought to play an important role in some pathologies of speech understanding difficulties. The purposes of the present study were to determine whether short silent gaps within a pure tone can be used to elicit mismatch negativity (MMN) as an objective measure of temporal resolution, and to investigate the relation between MMN and performance on a behavioral gap-detection task. The stimuli used for both tasks were 1-kHz sinusoids presented in a low-pass masking noise. Behavioral gap-detection thresholds were determined using an adaptive three-alternative forced-choice procedure. To elicit MMN, a series of deviant stimuli with varying gap durations was generated and presented in an oddball paradigm among standard stimuli without a gap. Only the gaps larger than the mean behavioral gap-detection threshold evoked a clear MMN. There was no clear relation between psychoacoustic and MMN thresholds.

Rhesus monkey model for Leishmania major transmitted by Phlebotomus papatasi sandfly bites.

Leishmaniasis research needs a near-human model for investigations of natural infection processes, immunological responses and evaluation of treatments. Therefore, we developed a reproducible system using Leishmania major Yakimoff & Schokhor (Trypanosomatidae: Kinetoplastida), the cause of Old World zoonotic cutaneous leishmaniasis (ZCL), transmitted to rhesus monkeys Macaca mulatta (Zimmerman) (Primates: Cercopithecidae) by sandfly bites of experimentally infected Phlebotomus papatasi (Scopoli) (Diptera: Psychodidae). Eight monkeys of presumed Indian origin (Leishmania naive) were exposed to bites of female sandflies that had been infected with L. major by membrane-feeding on human blood seeded with amastigotes isolated from hamster footpad lesions. Infection rates of membrane-fed sandflies averaged > 85% seven days after the infective feed, with uniformly high numbers of promastigotes in the stomodaeal valve region of the sandfly gut. Nodules and ulcerating dermal lesions developed on 7/8 monkeys 2-4 weeks post-bite and persisted for 3-7 months. Monkeys also developed satellite lesions beyond the area of sandfly bites on the head, but not on the chest. Three re-challenged monkeys developed lesions that healed faster than lesions from their primary challenges. After infection, monkeys developed delayed type hypersensitivity (DTH) responses to a panel of Leishmania skin test antigens (LSTA) and, when tested by ELISA and IFA, showed significant post-infection antibody titres which typically rose for approximately 170 days and then gradually receded during the next 100 days following the first challenge. After the second challenge, antibody titres spiked higher within approximately 50 days and receded more rapidly. In contrast, four rhesus macaques of Chinese origin developed no lesions following infected sandfly bites, although they raised antibodies and LSTA reactions, indicating subclinical infection.