[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.

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.

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.

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.

Ground-based near-infrared imaging observations of venus during the galileo encounter.

Near-infrared images of Venus, obtained from a global network of ground-based observatories during January and February 1990, document the morphology and motions of the night-side near-infrared markings before, during, and after the Galileo Venus encounter. A dark cloud extended halfway around the planet at low latitudes (>+/-40 degrees ) and persisted throughout the observing program. It had a rotation period of 5.5 +/- 0.15 days. The remainder of this latitude band was characterized by small-scale (400 to 1000 kilometers) dark and bright markings with rotation periods of 7.4 +/- 1 days. The different rotation periods for the large dark cloud and the smaller markings suggests that they are produced at different altitudes. Mid-latitudes (+/-40 degrees to 60 degrees ) were usually occupied by bright east-west bands. The highest observable latitudes (+/-60 degrees to 70 degrees ) were always dark and featureless, indicating greater cloud opacity. Maps of the water vapor distribution show no evidence for large horizontal gradients in the lower atmosphere of Venus.

The nature of the near-infrared features on the venus night side.

Near-infrared images of the Venus night side show bright contrast features that move from east to west, in the direction of the cloud-top atmospheric superrotation. Recently acquired images of the Venus night side along with earlier spectroscopic observations allow identification of the mechanisms that produce these features, their level of formation, and the wind velocities at those levels. The features are detectable only at wavelengths near 1.74 and 2.3 micrometers, in narrow atmospheric windows between the CO(2) and H(2)O bands. The brightest features have brightness temperatures near 480 Kelvin, whereas the darkest features are more than 50 Kelvin cooler. Several factors suggest that this radiation is emitted by hot gases at altitudes below 35 kilometers in the Venus atmosphere. The feature contrasts are produced as this thermal radiation passes through a higher, cooler, atmospheric layer that has horizontal variations in transparency. The 6.5-day east-west rotation period of the features indicates that equatorial wind speeds are near 70 meters per second in this upper layer. Similar wind speeds have been measured by entry probes and balloons at altitudes between 50 and 55 kilometers in the middle cloud layer. The bright features indicate that there are partial clearings in this cloud deck. The presence of these clearings could decrease the efficiency of the atmospheric greenhouse that maintains the high surface temperatures on Venus.

Cortical reorganization after acute unilateral hearing loss traced by fMRI.

Unilateral acoustic stimulation produces a functional MRI (fMRI)-blood-oxygenation-level-dependent (BOLD) response mainly in the contralateral auditory cortex. In unilateral deaf patients, the BOLD response is bilateral. We studied a subject with sudden hearing loss after cochlear nerve resection before and repeatedly after surgery. During normal bilateral hearing, contralateral cortical BOLD responses were found. Progressing compensatory reorganization with bilateral representation of unilateral stimulation was detected over a period of approximately 1 year.

Concurrent platinum-based chemotherapy and hyperfractionated radiotherapy with late intensification in advanced head and neck cancer.

PURPOSE: To determine whether a course of hyperfractionated radiation therapy concomitant with escalated radiosensitizing platinum compounds can be administered with acceptable morbidity and achieve a high rate of loco-regional control for Stage III and IV head and neck cancer and whether the patients can be tumor free at the primary site after initial therapy and cured by the additional chemoradiation without radical resection of the primary tumor. METHODS AND MATERIALS: Patients with Stage III/IV head and neck cancer were treated in this multicenter Phase II Study with 1.8 Gy fraction radiotherapy for 2 weeks, with escalation to 1.2 Gy b.i.d. hyperfractionation to 46.8 Gy. Concomitant continuous infusion cisplantinum (CDDP) 20 mg per meter square on day 1 to 4 and 22 to 25 was given. Reassessment by biopsy of primary and nodes was done. Patients with a complete response continued with hyperfractionated radiotherapy to 75.6 Gy with simultaneous carboplatinum (Carbo), 25 mg per meter square b.i.d. for 12 consecutive treatment days. Patients with residual disease at 46.8 Gy required curative surgery. Seventy-four patients were treated at the three institutions; 20 were Stage III and 54 were Stage IV. All patients had daily mouth care, nutritional, and psychosocial support. RESULTS: This regime was well tolerated. Eighty-five percent of toxicities were Grade 1 or 2 and there was only one Grade 4 hematologic toxicity. Late toxicities included xerostomia in 25 patients, dysphasia in 18, and mild speech impediment in 11. Biopsies of primary site were done after the first course of treatment in 59 patients. Neck dissections were performed in 35 patients. Forty-four of 59 (75%) primary sites and 16 of 35 (46%) lymph nodes had pathologically complete response (CR). Of the 74 patients, only 12 required surgical resection of the primary site. Thirty-five of the 50 node positive patients had neck dissections, 16 of these were CRs at surgery. At 4 years (median follow-up of 26 months), disease-specific survival is 63%. The actuarial survival for all patients is 51%. Patients with pathological CR after initial treatment have disease specific survival of 73% at 4 years vs. 48% of patients with partial response (PR) only. CONCLUSION: This study, developed on the basis of radiobiological and cell kinetic precepts, produced results that compare favorably with other reports of management of patients with advanced head and neck cancer. In comparison with our previous study, these results are comparable, not impressively better. The associated morbidity was somewhat worse.

A comparison of transiently evoked and distortion-product otoacoustic emissions in humans.

The measurement of transiently evoked otoacoustic emissions (TEOAEs) can identify a hearing loss exceeding 25-30 dB HL with high sensitivity. However, further quantification of the hearing loss is not possible, and the frequency specificity of TEOAEs has been questioned. Distortion-product otoacoustic emission (DPOAE) measurements are being developed for clinical use in the hope that they will be more frequency-specific than are TEOAEs. We have compared TEOAEs and DPOAEs in both normally hearing and hearing-impaired subjects with the purpose of learning more about the frequency specificity of these two types of emissions. In a first investigation, toneburst-evoked OAEs were compared to DPOAEs stimulated at 1, 2 and 4 kHz in ten ears without spontaneous otoacoustic emissions of ten normally hearing subjects. Input/output (I/O) functions of DPOAEs at frequency regions of 1 and 2 kHz were characterized by roll-overs and irregularities that were not present in either DPOAE I/O functions at 4 kHz or in TEOAE I/O functions at 1, 2 and 4 kHz. Mean slopes of the I/O functions increased with increasing frequency for DPOAEs and decreased for TEOAEs. In a second investigation, click-evoked OAEs and DPOAEs (stimulated by pure tones in the frequency range of 0.75-6 kHz) were measured in 42 ears of 21 normally hearing subjects and 128 ears of 64 subjects with varying degrees of sensorineural hearing loss. Results from both investigations revealed that the amplitude ratio between DPOAEs and TEOAEs changed systematically with frequency. DPOAE amplitudes became larger with increasing frequency and TEOAE amplitudes became smaller.(ABSTRACT TRUNCATED AT 250 WORDS)

Silicone stents in the management of inoperable tracheobronchial stenoses. Indications and limitations.

BACKGROUND: Various stent models have been developed for the treatment of inoperable stenoses of the central airways caused by external compression. Increasing use is made of the silicone stents designed by Dumon. We tested their technical feasibility, tolerance, and long-term efficacy in relieving respiratory symptoms in patients referred for endoscopic palliation of malignant disease. METHODS: All procedures were performed under general anesthesia with the use of the rigid bronchoscope. We inserted 38 stents in 31 patients (median age, 67 years; 25 men and 6 women) whose airways showed residual obstruction of > 50 percent of the lumen after laser resection of endobronchial tumor and/or mechanical dilatation of extrinsic compressions. RESULTS: Stent placement and removal--where necessary--were easy in all patients, but five stents inserted in three patients with short (< or = 2.5 cm) and conical stenoses migrated, necessitating emergency removal. In 27 of the remaining 28 patients, stent tolerance was excellent; 1 proximal tracheal stent (< 1 cm below the vocal cords) had to be removed because of otalgia and dysphagia. One lethal hemoptysis occurred within hours after a repeated laser therapy and removal of an indwelling stent. No other serious complications occurred. Immediate and lasting relief of dyspnea and improvement in performance status (Karnofsky scale, activity index) was achieved in 90 percent (28/31) of patients (p < 0.01). The influence of adjuvant radiotherapy on local tumor recurrence and survival was analyzed in a subgroup of ten patients with stage IIIB squamous cell carcinoma with comparable performance status. Five did not undergo adjuvant radiotherapy (group A) and five did (group B). In group A, four of five stents were occluded by tumor recurrence above or below the stent after a median follow-up of 2 months; in group B, zero of five were occluded (p < 0.05) after 4 months. Median survival was 4 months in group A and 6 months in group B; the difference did not reach significance. CONCLUSIONS: The silicone stents designed by Dumon are easily inserted and removed; they are also well tolerated and very efficacious in relieving respiratory symptoms caused by extrinsic airway compression. Short and conical stenoses present limitations for their use due to increased risk of migration. Combined treatment with laser resection, stent insertion, and subsequent radiotherapy is necessary to prevent local tumor recurrence and may improve survival.

The use of the covered Wallstent for the palliative treatment of inoperable tracheobronchial cancers. A prospective, multicenter study.

STUDY OBJECTIVE: To investigate the safety, efficacy, and tolerance of the covered Wallstent for the palliative treatment of inoperable tracheobronchial cancer. DESIGN: An 8-month prospective study employing either a rigid bronchoscope or a flexible delivery system for prosthesis insertion. SETTING: Multicentric setting involving four teaching hospitals in Switzerland and Germany. PATIENTS: Forty patients (29 men, 11 women), average age of 62 years, presenting with an inoperable tracheobronchial cancer. INTERVENTIONS: After partial airway recanalization with an Nd-YAG laser, the covered Wallstent was inserted 23 times using a rigid bronchoscope (Rigidstep device), and 27 times using a flexible delivery system (Telestep device) under fluoroscopic and endoscopic visualization. RESULTS: Clinical and endoscopic examination at 1, 30, and 90 days showed improvement in the bronchial lumen and in the dyspnea index. No serious complication (death, perforation, hemorrhage, inability to remove an improperly placed prosthesis) was observed during surgery. Late complications included migration (12%), inflammatory granulations or tumor regrowth at the tip of the prosthesis (36%), and symptomatic retention of secretion (38%). CONCLUSIONS: Compared with other tracheobronchial prostheses, notably the Dumon stent, the covered Wallstent presents the following advantages: insertion with visual guidance, treatment of extrinsic compressions and esophagobronchial fistulas, and little chance of migration when the prosthesis diameter is chosen correctly. The following disadvantages can be noted: high price; both repositioning and extraction of the released stent are more difficult, though certainly possible; and risk of granulations at the tips of the prosthesis and retention of secretions. Suggestions are made for potential improvements to the stent and insertion system that may result in a significant decrease in early and late complications.

The phenomenon of a high triglyceride response to an oral lipid load in healthy subjects and its link to the metabolic syndrome.

Excessive postprandial triglyceride (TG) responses despite normal fasting TG levels have been described in single cases within small groups of healthy subjects and in patients with obesity or precocious atherosclerosis, known to be associated with high insulin fasting levels. To clarify this association, fasting and postprandial TG and insulin levels were studied in 113 healthy young (25.7 +/- 2.6 years), normal weight (body mass index 20.8 +/- 2.3 kg/m2) male subjects who were selected from among 117 subjects on the basis of TG fasting levels < 200 mg/dl. After a 12-hour fast a standardized liquid lipid load was administered containing 58 g mainly saturated fat and 1,017 kcal energy. Both fasting TG values and postprandial TG peak values showed bimodal frequency distributions. Statistical analysis of fasting TG discriminated two groups: a low fasting TG group with normally distributed values < 150 mg/dl (mean +/- SEM: 79.5 +/- 2.7 mg/dl; n = 104) and a high fasting TG group > 150 mg/dl (194.5 +/- 7.2 mg/dl; n = 13). Likewise, two groups could be differentiated according to their maximal postprandial TG response (TG max) to the lipid load: (1) normal responders with TG max < 260 mg/dl (mean +/- SEM: 123 +/- 4.8 mg/dl; n = 96) and (2) high responders with TG max > 260 mg/dl (272.5 +/- 20.5 mg/dl; n = 17). Fasting TG and TG max were highly correlated (r = 0.745; p < 0.0001). However, 9 of 17 (53%) high responders had fasting TG < 150 mg/dl, which means that the prediction of high response is only 47.0% based on fasting TG values. Fasting insulin levels were significantly higher in high responders than in normal responders, whereas they did not differ between the low and high fasting TG group. In conclusion, the bimodal frequency distribution of TG max after a lipid load permitted the differentiation of two groups, normal responders and high responders, with higher fasting insulin levels, which might indicate a link to the metabolic syndrome.

Trigeminocardiac reflex during surgery in the cerebellopontine angle.

OBJECT: In different experimental studies authors have analyzed the autonomic responses elicited by the electrical, mechanical, or chemical stimulation of the trigeminal nerve system. The trigeminocardiac reflex (TCR) is a well-recognized phenomenon that consists of bradycardia, arterial hypotension, apnea, and gastric hypermotility. It occurs during ocular surgery and during other manipulations in and around the orbit. Thus far, it has not been shown that central stimulation of the trigeminal nerve can also cause this reflex. METHODS: The TCR was defined as clinical hypotension with a drop in mean arterial blood pressure (MABP) of more than 20% and bradycardia lower than 60 beats/minute. Pre-, intra-, and postoperative heart rate (HR) and MABP were reviewed retrospectively in 125 patients who underwent surgery for tumors of the cerebellopontine angle (CPA), and they were divided into two groups on the basis of the occurrence of the TCR during surgery. Of the 125 patients, 14 (11%) showed evidence of the TCR during dissection of the tumor near the trigeminal nerve at the brainstem. Their HRs fell 38% and their MABPs fell 48% during operative procedures as compared with preoperative levels. After cessation of manipulation, the HRs and the MABPs returned to preoperative levels. Risk factors for the occurrence of the TCR were compared with results from the literature. CONCLUSIONS: The authors' results show the possibility of occurrence of a TCR during manipulation of the central part of the trigeminal nerve when performing surgery in the CPA.

The influence of disappearing and reappearing spontaneous otoacoustic emissions on one subject's threshold microstructure.

The effects of a consistently disappearing and reappearing spontaneous otoacoustic emission (SOAE) at around 2280 Hz on microstructure for pure tones of varying durations in a 33 year-old woman with normal hearing was studied. The SOAE began to appear after 10-15 min in a quiet test room and increased in level by up to 22 dB over a 30-40-min period. The SOAE was measured every 12 to 15 min. Between measurements, the subject performed a signal detection task for pure tones with total durations varying from 20 to 320 ms. The signal frequencies were within a +/- 30-Hz range relative to the SOAE frequency. For signal durations of 40-320 ms, there was a local dip at the target SOAE frequency when it was either not detectable or its level was lower than -14 dB SPL. Subjective threshold levels were as much as 12 dB better than those obtained when the SOAE was -6 dB SPL or greater. The results suggest that a region of the cochlea with high sensitivity and instability can be put into self-oscillation producing an SOAE, possibly by a change of efferent activity. Hearing threshold is affected possibly due to adaptation or masking.

Suppression of tone burst evoked otoacoustic emissions in relation to frequency separation.

Tone burst evoked otoacoustic emissions (TBEOAEs) were measured for two tone bursts presented separately and as a two-tone burst complex to examine the linearity of TBEOAE generators for different frequency separations of the stimuli. The stimuli were: (a) tone bursts of 5-ms duration and center frequencies of 1, 1.5, 2 and 3 kHz; (b) complex stimuli with the 1-kHz tone burst combined digitally with each of the other specified tone bursts. Signals were delivered at 70 dB SPL using a non-linear processing method and at 60 dB SPL using a linear method to 21 ears of normally hearing adults. Spectra of TBEOAEs obtained with single-tone bursts were superimposed (composite) and compared to those of the two-tone burst complex. A close correspondence between the composite and complex spectra was present in all ears. However, the components on the higher-frequency slope of the 1-kHz spectral peak were reduced in the complex spectra obtained with a frequency separation of 0.5 kHz when compared to the corresponding composite spectra. The reduction was greater at a stimulus level of 70 dB SPL than with 60 dB SPL. The effect was smaller for a frequency separation of 1 kHz, and almost absent for the tone burst separation of 2 kHz. Thus, suppression leads to weak non-linear frequency superposition for higher-level, closely spaced stimuli.