A new method for drug application to the inner ear

Inner ear sensory cells are very susceptible to injuries and recovery after damage is very difficult. Recently several drugs including neurotrophic factors have been reported to protect against inner ear injury. The purpose of this experimental study is to find new methods for applying drugs to the inner ear that effectively protect against inner ear damage. Biodegradable hydrogel was used as a carrier for application of brain-derived neurotrophic factor (BDNF) into the inner ear of guinea pigs through the round window membrane. After application of BDNF the number of surviving spiral ganglion neurons increased following injury of inner ear hair cells and spiral ganglion neurons by ototoxic treatment. This result indicates that BDNF provides effective protection against inner ear damage and that biodegradable hydrogel is useful for application of drugs to the inner ear.     

Quantitative analysis of inner ear anomalies by high resolution CT scanning of the temporal bone

High resolution CT-scanning of the temporal bone revealed malformations of the labyrinthine capsule in 50 ears in our clinic from November 1980, to the end of 1984. Detailed assessment of the nature and extent of the abnormality allowed each ear to be awarded a mathematical score. Using statistical methods, the score was then correlated with the patient's hearing in that ear. By this method it was possible, with an 80% chance of being correct, to allocate a patient into one of two groups, i.e. partial deafness or total deafness.     

Ventral approach to rat inner ear preserves cochlear function

CONCLUSION: This technique enabled us to visualize the cochlea without causing damage. OBJECTIVE: The mammalian inner ear is difficult to approach surgically. This is particularly true in the cases of the rat and mouse, which both have small cochleae. Rat and mouse research is particularly important because their genomes are well characterized, and significantly similar to that of the human. The aim of the present study was to develop a method of accessing the rat cochlea without affecting its function. MATERIALS AND METHODS: In the ventral approach, a small hole was made for access to the scala tympani. Cochlear function was assessed through auditory brainstem response (ABR) threshold measurements. RESULTS: The ventral approach enabled the direct visualization of the tympanic bulla. Thus, the tympanic bulla could be easily opened in a manner that was benign to cochlear function. There was no significant difference in ABR threshold before and after surgery.     

A novel vestibular approach for gene transfer into the inner ear

The aim of gene transfer to the cochlea and vestibular organ is to protect the inner ear from different disorders. Although various vectors for gene delivery have been used with some success, there remains a need for a reliable transfer of genes into the inner ear without damaging cochlear function. Here, we have tested a novel application method for gene transfer into the rat inner ear in vivo using herpes simplex virus type-1(HSV-1)-based amplicon vectors. Our goal was to find an entry route into the inner ear that leaves its function intact. Besides other non-invasive and invasive application techniques, we applied the viral vector via injection through a small opening of the utriculus. Using this method, efficient -galactosidase reporter gene expression was achieved in nearly all neurons in the vestibulum and cochlea, without functional hearing deficits. At the time point of maximal expression 5 days after injection, -galactosidase activity was also observed in axonal fibres and synaptic endings close to inner and outer hair cells. Our results thus describe an efficient and reliable protocol for short-term expression of potential therapeutic genes in the neuronal compartment of the inner ear.     

Preservation of basal inner ear structures in cochlear implantation

The aim of this report was to examine basal trauma in implanted human temporal bones and discuss modified approaches to the basal cochlear turn to avoid destruction of basal cochlear structures. Thirty-three human temporal bones were implanted with four different cochlear implant electrode arrays manufactured by MED-EL using either a caudal approach cochleostomy or round window membrane insertions. All specimens were processed with a special histological technique that allows sectioning of undecalcified bone with the electrode in situ. All bones were evaluated histologically in terms of basal cochlear trauma. Two pathomechanisms of basal trauma could be distinguished and were evaluated separately, buckling of the basal end of the array and trauma by drilling. Using the caudal approach cochleostomy, the total percentage of destructive basal trauma was 48% compared to less than 15% when performing round window membrane insertions. Although it is still unclear whether basal cochlear trauma influences apical cochlear function or not, adapted surgical procedures and no forceful insertion maneuvers should be used when performing cochlear implantations with hearing preservation.     

Diving injuries to the inner ear

Summary Two skin divers and 7 SCUBA divers, all men, aged 21–33 years, are presented. The injury occurred at shallow depths and difficulties with pressure equilibration to the ears were a common complaint. Vertigo and hearing losses. When a perilymph fistula is suspected and decompression sickness can be in the round, the other in the oval window. The latter patient also had a perforated ear drum on the same side, but his hearing normalized after surgical repair of the fistula and perforation. The others suffered lasting sensorineural high tone losses. When a perilymph fistula is suspected and decompression sickness can be ruled out, surgery within two days is recommended if bed rest does not prove effective.     

Delivery of drugs to the inner ear

PURPOSE OF REVIEW: Inner ear delivery of medicines has been a rapidly expanding field in otolaryngology. This technique provides a minimally invasive way of managing a number of otolaryngologic diagnoses and promises to provide a therapeutic option for previously untreatable disorders. The purpose of this review is to examine the literature that has been published recently (since January of 2005) in this field and to explore how this new literature has impacted on current practices. RECENT FINDINGS: While there was a significant volume of work done in this area from 1995 to 2004, publication in this area has slowed considerably. The literature focuses on two areas: the treatment of Ménière's disease with gentamicin and the treatment of sudden sensorineural hearing loss with steroids. The most promising area in this field, which is the development of new medicines to treat a variety of disorders, has not progressed over the last 2 years. SUMMARY: Recent peer-reviewed publications have not had a significant impact on the transtympanic treatment of Ménière's disease or sudden sensorineural hearing loss. We will review the current practices in these two areas, discuss the newest developments and examine how we can progress the field over the next several years.     

An approach for precise three-dimensional modeling of the human inner ear

For further morphological and physiological research, it is vital to establish precise three-dimensional models of the whole inner ear including the details of the membranous components. With the system of a projector and a high-resolution digital camera, 2 complete serial unstained celloidin sections of fresh human temporal bones were digitized as high-resolution images which were then sorted, calibrated, aligned and segmented using the 3D-Doctor software. Finally, 2 precise three-dimensional models of the inner ear were generated by simple surface rendering. The contours of tiny structures such as the crista ampullaris, the macula utriculi and the macula sacculi could be observed clearly. Our study suggests that it is technically feasible to employ complete serial unstained celloidin sections for precise three-dimensional reconstruction and that this helps reduce errors and laboratory workload. Moreover, the use of a high-resolution digital camera and the autoalignment function of 3D-Doctor further increase the accuracy of the models.     

X-ray microanalysis of inner ear fluids in the embryonic and newborn guinea pig

Summary In energy-dispersive histograms, changes in the relative peak intensities were followed, especially Cl and K, which indicate the maturation of endolymph. The maturation of endolymph in the guinea pig occurs prior to birth. In X-ray histograms, distinct peaks for Cl and K, but also for Na, were observed approximately 20 days before birth (DBB). The lesser relative peak intensities for Cl and K as compared with mature endolymph indicate an immature endolymph composition at this stage of development. The relative peak intensities of Cl and K increased at approximately the 10-DBB stage and showed similar values as at birth.Supported by grants from the Swedish Medical Research Council (project 12X-720) and the Foundation Tysta SkolanPresented at the 18th Workshop on Inner Ear Biology in Montpellier/La Grande Motte, September 14–16, 1981     

Homing of lymphocytes to the inner ear.

The migration of lymphocytes to the inner ear was studied during an immune response in the cochlea. Sensitized lymphocytes from peripheral blood, neck lymph nodes and spleen from strain 13 inbred guinea pigs were labelled with 51Cr and injected intravenously into strain 13 recipients undergoing an inner ear immune response. Eighteen hours later the temporal bones and immune organs of the recipients were assayed for radioactivity to detect the infiltration of labelled cells. In addition autoradiography was performed to localize labelled cells in the inner ear. More lymphocytes from the peripheral blood entered the inner ear during the immune response than spleen or lymph node cells. This indicates that the inner ear comes under the immuno-surveillance of the peripheral circulation in response to antigenic stimulation. Most labelled lymphocytes were observed in the basal turn of the scala tympani and in and around the spiral modiolar vein of the challenged cochlea. A few cells were seen also in the control cochleas but almost all where inside the blood vessels. This pattern suggests that the blood vessels of the spiral modiolar vein are the initial site through which lymphocytes entered the inner ear.     

Application of argon laser to the inner ear

The effects of argon laser irradiation on the inner ear were studied morphologically. The stria vascularis showed focal coagulation, vesicle formation, perforation and atrophy after irradiation through the otic capsule. These changes vary according to the power and duration of irradiation. Atrophy of the stria vascularis can be produced without injuring the organ of Corti, by suitable application of the laser beam. The round window membrane transmits the argon laser. Tissues in the hook region and a part of the lower basal turn demonstrated changes of varying degree. Loss of the nerve fibres was observed in the osseous spiral lamina, which was fractured and dislocated. Irradiation through the stapedectomized oval window destroyed the macula sacculi without rupturing the saccular wall.     

A new immunohistochemical method for the detection of gentamicin in inner ear fluid compartments

A new method was developed for frozen section detection of antigens that natively occur in the cochlear peri- and endolymph. A combination of immunohistochemistry and immunoblot assay enabled topological and quantitative detection of small and hydrophilic molecules (such as the aminoglycoside antibiotics) in frozen sections of the inner ear compartments (scala tympani, scala vestibuli and cochlear duct). A selective localization is possible in the peri- and endolymphatic region of each coil of the cochlea. During sectioning of the cochlea, a small piece of a nitrocellulose membrane is placed to the surface of the intersection and briefly warmed. The sections are cut, simultaneously attached to a nitrocellulose membrane on which the aminoglycoside antibiotics remain adsorbed without any fixation procedure. Using this method, immunoincubation to detect gentamicin was performed in a way usually done in western blot analysis. Results with two different enzyme reactions with the enzyme conjugated to a second antibody (i.e., dye as substrate and the chemiluminescence detection system) are presented and compared. This histoimmunoblot assay provides a general non-radioactive and sensitive immunohistochemical tool for the localization of compounds occurring in extracellular body fluid compartments. For inner ear research this method now enables the investigation of the penetration and distribution of therapeutics in peri-and endolymphatic sites and can even be applied to separately quantifying concentrations of a substance in different coils of the same cochlear section.     

内耳结构异常患者人工耳蜗植入术的疗效观察

目的分析研究内耳结构异常患者人工耳蜗植入术的安全性及手术后的疗效情况。方法选取2011.07-2015.06在我院住院接受人工耳蜗植入的17例内耳结构异常患者的临床资料,其中语前聋14例,语后聋3例,针对内耳结构异常情况采用不同术式。用听觉分级行为标准(Categorise of Auditory Performance,CAP)、言语可懂度分级标准(Speech Intelligibility Rating,SIR)进行术后效果评估。选取24例同期接受人工耳蜗植入的内耳正常的语前聋患者作为对照组,分析并比较两组患者手术并发症及术后疗效。结果:17例患者手术顺利,术后出现1例眩晕,所有患者术后均无脑脊液耳漏、面瘫等并发症。内耳结构异常语前聋患者术后CAP和SIR值分别为5.8±1.4、3.5±1.1;对照组CAP和SIR值分别为6.9±1.3、3.8±0.9,两者差异无统计学意义(P>0.05)。结论内耳结构异常非人工耳蜗植入术的绝对禁忌证,根据异常程度制定个性化的手术方案,可以减少并发症的发生。内耳结构异常语前聋患者术后言语康复情况、对声音的自发性觉察能力与耳蜗形态正常患者术后无明显差异。     

Symposium: new data for noise standards. 3. Organ culture of the mammalian inner ear: a tool to study inner ear deafness

Twelfth gestation day kreisler otocysts were explanted into an organ culture system and allowed to develop for nine days. The homozygotic (kr/kr) kreisler otocysts showed significant developmental differences when compared to the development that occurred in the organ culture specimens of the otocysts of its heterozygotic (+ /kr) litter mates. The differences in development observed in vitro were the same major developmental differences that had been observed in vivo. The phenotypic expression of the kreisler genome has expressed itself in vitro in the homozygotic kreisler otocyst.