[Hearing loss in patients with Fabry disease]. / Hörstörungen bei Morbus Fabry.

BACKGROUND: Fabry disease is an X-linked lysosomal storage disease involving deficient activity of alpha-galactosidase A, which leads initially to pain, and later to renal insufficiency, cardiomyopathy and stroke. Until now few details are available on hearing impairment in patients with Fabry disease, and especially few relating to female patients. PATIENTS AND METHODS: We examined 43 female and 29 male patients. In this study we looked into the question of whether and to what extent patients of both genders are affected by hearing impairment. RESULTS: Hearing loss is characteristic being more severe at high frequencies frequencies. Overall, 22 female and 15 male patients were found to have suffered a hearing loss. Patients with severe symptoms of Fabry disease usually demonstrate more prominent hearing losses. CONCLUSIONS: Both men and women with Fabry disease are affected by hearing impairment. It seems that the hearing loss is less marked in female than in male patients. Children with Fabry disease complain of tinnitus more frequently than other children and quite early in the course of the disease.

Deficient membrane integration of the novel p.N14D-GJB2 mutant associated with non-syndromic hearing impairment.

Mutations in GJB2, the gene encoding for the Gap Junction protein Connexin 26 (Cx26), have been established as the major cause of hereditary, non-syndromic hearing impairment (HI). We report here the identification of a novel point mutation in GJB2, c.40A>G [p.N14D], detected in compound heterozygosity with the c.35delG mutation in two brothers with moderate non-syndromic sensorineural HI. The mother who carried one wildtype and a p.N14D allele displayed normal hearing. The mutation leads to substitution of the neutral amino acid asparagine (N) by the negatively charged aspartic acid (D) at amino acid number 14, a position that is conserved among Cx26 of different organisms and among many other connexin isoforms. To investigate the impact of this mutation on protein function, Cx26 activity was measured by depolarization activated hemichannel conductance in non-coupled Xenopus laevis oocytes. Oocytes injected with the p.N14D mutant cRNA showed strongly reduced currents compared to wildtype. Coinjection of wildtype and mutant cRNA at equimolar levels restored the conductive properties supporting the recessive character of this mutation. Total Cx26 protein expression and cell surface abundance examined by western blotting and by quantitative immunoassays revealed that the hemichannel was properly synthesized but not integrated into the plasma membrane. In this study we have shown that the GJB2 mutation p.N14D is associated with recessively inherited HI and exhibits a defective phenotype due to diminished expression at the cell surface.

[Diagnosis and therapy of auditory synaptopathy/neuropathy]. / Diagnostik und Therapie der auditorischen Synaptopathie/Neuropathie.

Pathological auditory brainstem responses (lack of responses, elevated thresholds and perturbed waveforms) in combination with present otoacoustic emissions are typical audiometric findings in patients with a hearing impairment that particularly affects speech comprehension or complete deafness. This heterogenous group of disorders first described as "auditory neuropathy" includes dysfunction of peripheral synaptic coding of sound by inner hair cells (synaptopathy) and/or of the generation and propagation of action potentials in the auditory nerve (neuropathy). This joint statement provides prevailing background information as well as recommendations on diagnosis and treatment. The statement focuses on the handling in the german language area but also refers to current international statements.

Possibilities and limitations of current stereo-endoscopy.

BACKGROUND: Stereo-endoscopy has become a commonly used technology. In many comparative studies striking advantages of stereo-endoscopy over two-dimensional presentation could not be proven. To show the potential and fields for further improvement of this technology is the aim of this article. METHOD: The physiological basis of three-dimensional vision limitations of current stereo-endoscopes is discussed and fields for further research are indicated. New developments in spatial picture acquisition and spatial picture presentation are discussed. RESULTS: Current limitations of stereo-endoscopy that prevent a better ranking in comparative studies with two-dimensional presentation are mainly based on insufficient picture acquisition. CONCLUSION: Devices for three-dimensional picture presentation are at a more advanced developmental stage than devices for three-dimensional picture acquisition. Further research should emphasize the development of new devices for three-dimensional picture acquisition.

[Comparative study of spatial imaging techniques in stereo-endoscopy]. / Vergleichende Untersuchung räumlicher Darstellungsverfahren in der Stereoendoskopie.

PURPOSE: This study compares the two-dimensional presentation of stereo-endoscopic video data with three-dimensional presentation using polarization glasses and three-dimensional presentation with an autostereoscopic display. The aim of this study was to evaluate possible advantages of the three display technologies. MATERIAL AND METHODS: Fifty-nine test persons untrained in endoscopy had to complete three endoscopic tasks with different levels of difficulty. Each test involved a new presentation method. Different measurements were noted such as speed of task completion, accuracy of task performance, and quantity of solved tasks. The data collected were statistically evaluated. RESULTS: Neither sex, handedness, nor level of stereopsis had any statistically significant impact on the test results. The differences between the three presentation methods of stereo-endoscopic pictures were not statistically significant. CONCLUSION: Similar results were achieved with all three presentation methods. None of the presentation methods was significantly superior in the values measured. A final assessment of the possibilities of spatial endoscopy should await future technological developments in endoscopic devices (e.g., picture acquisition).

Comparison between three-dimensional presentation of endoscopic procedures with polarization glasses and an autostereoscopic display.

BACKGROUND: Most endoscopic procedures are done with a two-dimensional (2D) view or a spatial presentation with polarization glasses. A new method of presenting three-dimensional (3D) spatial views is the autostereocopic display. We compared the performances of untrained test persons using these methods. METHODS: We designed three tests that had to be performed with one of the presentations. We used a Karl Storz 3D set with a 0 degrees stereooptic and a grasper. The autostereoscopic display was the Dresden 3D display. The 59 test persons were students who had never before worked with endoscopic devices. RESULTS: There were few differences between the tests, and none were statistically significant. The results with 2D were slightly better than those with polarization glasses, and the results with polarization glasses were slightly better than those with the autostereoscopic display. CONCLUSIONS: There are few differences between the procedures. A true spatial view is limited by the similarity of the two half-pictures.

A novel microperfusion system for the long-term local supply of drugs to the inner ear: implantation and function in the rat model.

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

Thyroid hormone-deficient period prior to the onset of hearing is associated with reduced levels of beta-tectorin protein in the tectorial membrane: implication for hearing loss.

The genes for alpha- and beta-tectorin encode the major non-collagenous proteins of the tectorial membrane. Recently, a targeted deletion of the mouse alpha-tectorin gene was found to cause loss of cochlear sensitivity (). Here we describe that mRNA levels for beta-tectorin, but not alpha-tectorin, are significantly reduced in the cochlear epithelium under constant hypothyroid conditions and that levels of beta-tectorin protein in the tectorial membrane are lower. A delay in the onset of thyroid hormone supply prior to onset of hearing, recently described to result in permanent hearing defects and loss of active cochlear mechanics (), can also lead to permanently reduced beta-tectorin protein levels in the tectorial membrane. beta-Tectorin protein levels remain low in the tectorial membrane up to one year after the onset of thyroid hormone supply has been delayed until postnatal day 8 or later and are associated with an abnormally structured tectorial membrane and the loss of active cochlear function. These data indicate that a simple delay in thyroid hormone supply during a critical period of development can lead to low beta-tectorin levels in the tectorial membrane and suggest for the first time that beta-tectorin may be required for development of normal hearing.

Can testosterone alone maintain the gonadotrophin-releasing hormone antagonist-induced suppression of spermatogenesis in the non-human primate?

The combination of gonadotrophin-releasing hormone (GnRH) antagonist and delayed testosterone substitution provides a promising approach towards male contraception. However, the GnRH antagonists used clinically so far cause side-effects and have to be administered continuously. We therefore used the non-human primate model to see whether the GnRH antagonist cetrorelix (which exhibits a favourable benefit-to-risk ratio in terms of anti-gonadotrophic action in normal men) induces complete and reversible suppression of spermatogenesis and whether GnRH antagonist-induced suppression of spermatogenesis can be maintained by testosterone alone. Four groups of adult cynomolgus monkeys (Macaca fascicularis; five per group) were injected daily with 450 micrograms cetrorelix/kg ([N-acetyl-D-2-naphthyl-Ala1, D-4-chloro-Phe2, D-pyridyl-Ala3, D-Cit6, D-Ala10]-GnRH). Group 1 received the GnRH antagonist for 7 weeks followed by vehicle administration for another 11 weeks; group 2 was treated with GnRH antagonist for the entire 18 weeks with each animal receiving a single testosterone implant during weeks 11-18 to restore the ejaculatory response to electrostimulation; group 3 received the GnRH antagonist for 18 weeks and testosterone buciclate (TB) was injected during week 6 of GnRH antagonist treatment; group 4 was subjected to GnRH antagonist administration for 7 weeks and received TB (200 mg/animal) during week 6. Under GnRH antagonist treatment alone serum concentrations of testosterone were suppressed. TB maintained testosterone levels two- to fourfold above baseline levels in groups 3 and 4 and prevented the recovery of LH secretion for about 20 weeks after GnRH antagonist withdrawal, whereas inhibin levels increased significantly from week 8 onwards. Group 2 animals were azoospermic during weeks 12-18 of GnRH antagonist administration. The TB-replaced groups developed azoospermia or became severely oligozoospermic. Quantitation of cell numbers by flow cytometry during weeks 6 and 18 revealed that TB (groups 3 and 4) had prevented a further decline of germ cell production compared with group 2 but had maintained the spermatogenic status present at week 6 (onset of TB substitution). All inhibitory effects of cetrorelix and/or TB were reversible after cessation of treatment. These findings demonstrate that cetrorelix reversibly inhibits spermatogenesis in a non-human primate model. Although TB maintained the GnRH antagonist-induced suppression of spermatogenesis, azoospermia was not achieved. This latter effect may reflect either a direct spermatogenesis-supporting effect of the high dose of TB or the partial recovery of inhibin secretion (indirectly reflecting FSH secretion) or a combination of both.(ABSTRACT TRUNCATED AT 400 WORDS)