Local antibiotic administration decreases risk of inner ear damage in effodation

BACKGROUND: Mobilising the stapes via the removal of the tympanosclerotic plaques from the oval window niche (effodation) and stapedectomy or malleovestibulopexy are the different procedures generally available for the surgical therapy of stapes fixation due to tympanosclerosis. These techniques bear a significant risk of sensory hearing loss. Here we analyse our results using the mobilisation technique together with locally applied antibiotics. PATIENTS: Nineteen ears in seventeen patients with tympanosclerosis involving the stapes and its footplate which underwent stapes mobilisation between 1991 and 1999 have been investigated retrospectively. According to the literature this operation has a high risk of cochlear hearing loss. To reduce this risk, azlocillin was instilled locally during removal of tympanosclerotic plaques. RESULTS: Different operation techniques have been used: classic type III with placement of a cartilage disc on the head of the stapes (4), interposition of the incus (3), interposition of the head of malleus (1), interposition of a ceramic-PORP (6) and cartilage columella in cases of significant stapes footplate erosion (3). In two operations the chain was intact and no reconstruction was necessary. Pure-tone-audiometry showed no significant decrease of bone-conduction thresholds. Preoperatively 4 (21.1%) ears had an average air-bone-gap < or = 30 dB, while postoperatively 15 (78.9%) ears had this level of hearing. CONCLUSIONS: Until the exact causes of the loss of hearing after mobilisation or stapedectomy in cases of tympanosclerosis are known, the local administration of antibiotics is certainly recommended, bearing in mind the initial hypothesis that infection may be jointly responsible for cochlear hearing loss on mobilisation or stapedectomy in cases of tympanosclerosis.     

Histopathology of chloroform-induced inner ear damage

Inner ear function loss was caused in guinea pigs and rats by injecting chloroform into the middle ear. After symptoms for cochlear and vestibular deficit had been registered, the animals were permitted to survive for one day to five months. Ear histopathology was then studied in celloidin sections. In both species, hair cells and afferent nerve fibers were intact at all survival times. The acute stage of functional loss in guinea pigs was associated with inner ears of normal histological appearance. Within days after chloroform injection a severe otitis media developed which led to fibrous occlusion of the round window and eventually to new bone growth in the middle ear space around the otic capsule. A secondary labyrinthitis was also observed, resulting in endolymphatic hydrops at longer survival times. Different histopathological changes were seen in rats. The tectorial membrane appeared swollen in all cases, the swelling being more severe in more apical turns at longer survival times. It is concluded that only secondary sequela of the initial functional insult can be detected by standard light microscopic histopathology. Chloroform does not cause a chemical labyrinthectomy as previously assumed, although it is severely ototoxic.     

Experimental vibratory damage of the inner ear

The aim of the experiment was to determine the effect of whole-body vibration on the inner ear. The investigations were carried out on 40 guinea pigs, subjected to sinusoidal vibration (10 Hz/5 mm/1.4 g rms) for 1 to 6 months in a noiseless apparatus. Cochlear microphonic measurements were done with a phase-sensitive detection technique for the levels 70, 80 and 90 dB and the frequencies of 0.26, 0.5, 1 and 2 kHz from the apex of the cochlea and for 4 and 8 kHz from the region of the round window. Analysis of 1,440 measurements suggested the possibility of damage appearing in the upper turnings of the cochlea. The subsequent morphological analysis was based on the estimation of the state of the hair cells (a three-degree scale of injury) in a Zeiss DSM 950 scanning microscope and of the structure of the fibers of the acoustic nerve in a Zeiss EM 900 transmission microscope. Vibration-induced changes were seen in all the examined inner ears of the experimental groups. Hair-cell damage was more often seen in the region of the apex, spreading gradually in the direction of the base and from the circumference (outer hair cells of the third row) to the modiolus. The most characteristic vibrational changes of the acoustic nerve fibers occurred in 100% of the examined myelin sheaths and were visible as decreases in their electrodensity. The changes in both the assessed elements of the inner ear appeared simultaneously but independently and were directly connected with the duration of the experiment. The results obtained allow an explanation of the mechanism of hearing loss in persons subjected to whole-body vibration. The damages done to the inner ear structures may cause a worsening of hearing there, especially in the low and medium frequencies.     

Electrophysiological evaluation of chloroform-induced inner ear damage

Summary Local placement of chloroform in either the external or the middle ear has been previously reported to induce a chemical labyrinthectomy. In order to examine the value of this effect as a research tool, we injected chloroform into the middle ears of guinea pigs and rats. Cochlear damage was assessed by electrocochleography (ECochG) and auditory brainstem response (ABR) audiometry. Both species developed complete deafness within a few hours after instillation of the chloroform. The deafness was permanent in the guinea pigs, whereas there was a partial recovery of auditory function in the rats. The survival rate of the auditory nerve fibers was estimated by measuring the ABR evoked by electrical stimulation via the scala tympani (EABR). A normal EABR recruitment pattern suggested that the main chloroform effect was located peripheral to the afferent axons. In conclusion, chloroform must be considered a severely ototoxic agent when applied locally.Dr. Hu Ke is on academic leave from the Department of Otolaryngology, Peking Union Medical College Hospital, Beijing, China.Supported by Pacific Otolaryngology Foundation and Medical Research Council, Canada     

Electrophysiological evaluation of chloroform-induced inner ear damage

Local placement of chloroform in either the external or the middle ear has been previously reported to induce a chemical labyrinthectomy. In order to examine the value of this effect as a research tool, we injected chloroform into the middle ears of guinea pigs and rats. Cochlear damage was assessed by electrocochleography (ECochG) and auditory brainstem response (ABR) audiometry. Both species developed complete deafness within a few hours after instillation of the chloroform. The deafness was permanent in the guinea pigs, whereas there was a partial recovery of auditory function in the rats. The survival rate of the auditory nerve fibers was estimated by measuring the ABR evoked by electrical stimulation via the scala tympani (EABR). A normal EABR recruitment pattern suggested that the main chloroform effect was located peripheral to the afferent axons. In conclusion, chloroform must be considered a severely ototoxic agent when applied locally.     

Mechanism of inner ear damage due to hyperlipidemia

Some clinical data concerning the relationship between hyperlipidemia and sensorineural hearing loss have been reported, however, definite mechanism causing pathological changes in the cochlea and hearing loss has not yet been clarified. We studied the mechanism of hearing loss due to hyperlipidemia in rabbits by ABR hearing examination, biochemical study of the sera, observation of the inner ear morphology by Sem and Tem. We suggest that the decreased blood supply in the inner ear during hyperlipidemia because of increased platelet aggregation and blood viscosity may be responsible for the inner ear damage. At the same time, a high lipid peroxide level in the serum and the inner ear, as well as the metabolic disorder of lipids in the inner ear may also contribute to the development of hearing loss.     

Viral origin of postnatally acquired inner ear damage

Experimental and clinical data exist which point at a possible role of herpes virus infections in postnatally acquired inner ear disturbances. The presence of viral DNA in the inner ear and vestibular organ of experimentally infected mice and pigs suggests that not only primary infections but also the reactivation of latent herpes viruses can cause severe inner ear damage. Serological examinations are presented and therapeutic considerations discussed.     

Fixation of soft tissue surrounded by bone with microwave irradiation: electron microscopic observation of guinea pig inner ear

When electron microscopy is performed on organs such as the inner ear that cannot be removed immediately after decapitation of animals, it is necessary to fix the target organ or tissue by systemic or regional perfusion fixation. However, such methods of fixation can increase vascular pressure or perilymphatic pressure, making it difficult to perform precise morphological observation of the vascular endothelial cells and membranous labyrinth. We recently attempted fixation of the cochlea by microwave irradiation. Guinea pigs were decapitated. The bullas were then removed from each animal and fixed in a mixture of 2% paraformaldehyde and 0.5% glutaraldehyde. Microwave (300 W) irradiation was then applied to the specimen for 1 minute. The fixative was immediately replaced with new fixative (4 degrees C). This sequence of manipulations was repeated 10 times, for a cumulative microwave irradiation time of 10 minutes. During the microwave irradiation period, the fixative temperature was kept at about 30 degrees C. After the last round of irradiation, the specimens were kept immersed in the fixative for 1 hour. After a small slit was created in the bone on the lateral wall of the cochlea, the specimens were post-fixed in osmic acid and embedded in Epon 812. Each specimen was cut into halves along the plane containing the modiolus of the cochlea. After the bone on the lateral wall of the cochlea was cut off under a stereoscopic microscope, ultrathin sections were prepared for observation under a transmission electron microscope. With this technique, the stria vascularis and the organ of Corti were fixed to a degree comparable to or better than that achieved with the conventional method of fixation. Fixation with microwave irradiation is relatively simple and can solve the problems associated with perfusion fixation, and thus provides an excellent means of fixation. This technique appears to be particularly promising for fixation for soft tissue surrounded by bone.     

ALH-L1005 attenuates endotoxin induced inner ear damage

Objective

To assess whether this compound (ALH-L1005) is conceivably an effective agent in protecting against cochlear damage induced by LPS.

Materials and methods

Tube formation using human umbilical vein endothelial cell (HUVEC) and matrix metalloproteinase (MMP)-9 inhibition assay was performed. 24 guinea pigs were randomly divided into three groups. Intratympanic instillation of LPS (n = 8) as negative control, instillation of oxytetracycline 1 h after LPS as positive control (n = 8), and intratympanic instillation of ALH-L1005 (n = 8) 1 h after LPS were considered experimental group. Evaluation by auditory brainstem response (ABR) measurement, cochlear blood flow, and blood–labyrinth barrier (BLB) permeability were performed. Cochlear hair cells were observed by field emission-scanning electron microscopy (FE-SEM). MMP-9 activation was measured by gelatin zymography.

Results

For HUVEC, the tube formation was suppressed in a dose dependant manner. ALH-L1005 inhibited the MMP-9 activity prominently. It also attenuated the elevation of LPS-induced hearing threshold shift and recovery of CBF. By FE-SEM, cochlear hair cells could be preserved in experimental group. ALH-L1005 significantly reduced the BLB opening compared to LPS group. Active MMP-9 expression could be detected in the LPS group. In contrast to ALH-L1005 group, active MMP-9 expression was not detected.

Conclusion

Our results conclude that ALH-L1005 showed a protective effect in the cochlear lateral wall damage induced by LPS.     

Lightning causing inner ear damage and intracranial haematoma

Lightning can transmit energy by way of the telephone network to the middle and the inner ear and thus cause pronounced injuries. In the patient mentioned here, the middle ear remained intact, while the inner ear was the seat of widespread damage combined with vascular rupture, the latter causing the formation of an intracranial haematoma. This was originally interpreted wrongly as a neoplasm.     

Analysis of immunocompetent cells following inner ear immunostimulation

Immunohistochemical methods were used to investigate the development of inner ear immunocompetent cells in healthy, BALB/c mice over a 3-week period as a result of a secondary inner ear response against keyhole limpet hemocyanin. Antibodies against murine macrophages and granulocytes (anti-Mac-1), T-cells (anti-Lyt-1, anti-Lyt-2), and immunoglobulins (anti-IgM, anti-IgG, anti-IgA) were used. Mac-1 positive (Mac-1+) cells were observed at 6 hours post-challenge in the endolymphatic sac and cochlea and rapidly increased in both sites. Lyt-1+ cells gradually increased in the endolymphatic sac after challenge, peaking at 2 and 3 weeks post-challenge. In the cochlea, Lyt-1+ cells were detected at 1 day post-challenge and then increased. Lyt-2+ cells were detectable in the endolymphatic sac and the cochlea by 3 weeks post-challenge. The predominant immunoglobulin-bearing cell in the endolymphatic sac was IgG, followed by IgM, with IgA seen late in the response. We conclude that the inner ear has the capacity to mount an immune response through the accumulation of the needed immunocompetent cells for antigen processing, antibody production, and modulation of the response through T-helper and suppressor cell activity.     

电离辐射对内耳的迟发性损害

为探讨电离辐射所致内耳迟发性损伤的特点和机理，观察了分割剂量６０Ｃｏγ射线照射豚鼠颞骨，当总剂量达６０Ｇｙ后８个月期间内耳功能和形态变化。形态研究应用光镜、扫描电镜与透射电镜，而功能测定采用耳蜗电图（ＥＣｏｃｈＧ）和眼震电图（ＥＮＧ）技术。结果发现：辐射耳照射前ＣＡＰ（复合动作电位）反应阈平均３５．６７±６．７８ｄＢ（ｘ±ｓ），总剂量结束后第一天为４１．１７±７．７６ｄＢ，３个月后４７．００±８．８２ｄＢ，８个月后７１．００±７．６３ｄＢ。放射结束后第一天与照射前比较无统计学差异（Ｐ＞０．０５），３个月后ＣＡＰ反应阈上升，８个月后听觉功能损害更明显（Ｐ＜０．０１）。辐射前眼震持续时间４０．００±５．４４秒，辐射后８个月２２．７１±７．３９秒，差异非常显著（Ｐ＜０．０１）。病理变化特点：耳蜗血管纹萎缩、变性，毛细血管数目减少，血管壁增厚，内皮细胞受损，细胞连接破坏；外毛细胞变性、坏死，底回毛细胞损伤率明显高于二、三回；前庭感觉细胞变性。结果表明：放射治疗剂量可致内耳的迟发性损害，内耳微血管辐射损伤后氧供和新陈代谢障碍可能是主要的致病机理。     

A novel technique for inducing local inner ear damage

With significant development of mouse genomics and the availability of transgenic and knockout mice, the mouse will be the preferred animal model for inner ear research. However, few studies have used mice as experimental animals for examination of hair cell degeneration, because of their relative resistance to ototoxic agents and difficulties in surgical treatment. This study presents a model for induction of apoptotic cell death in sensory epithelia of the mouse inner ear using injection of neomycin into the posterior semicircular canal. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay revealed that local application of neomycin produced sufficient induction of apoptotic cell death in both auditory and vestibular epithelia over a definite time course. Supplementation of the general caspase-inhibitor significantly reduced induction of TUNEL-positive cells, indicating caspase-dependency of apoptotic cell death observed in the present model. In addition, the approach to the posterior semicircular canal was an easy technique, and sham-operation induced no significant induction of TUNEL-positive cells. This model, hence, enables the use of various genetic tools in studies for mechanisms of hair cell apoptosis.     

Feasibility of inner ear gene transfer after middle ear administration of an adenovirus vector

BACKGROUND: Several groups demonstrated in animal experiments that gene transfer is a feasible tool for inner ear intervention. Various approaches for inoculation of vectors have been successfully used for inner ear gene therapy. One possible way to reduce the risk of hearing loss following the opening of the cochlea for application of the vector into the perilymphatic space is to deliver vectors through the round window. This study was designed to determine whether middle ear application of an adenoviral vector is a feasible approach to inoculate vectors and lead to transduction of cells in the inner ear. METHODS: A unilateral middle ear application of an adenoviral vector was performed in 4 guinea pigs directly on the round window membrane (RWM) and in 4 additional animals by placing a cotton patch soaked with the vector solution on the RWM. The expression of a reporter gene (lacZ) was used to localize vector-transduced cells. RESULTS: Only one out of 8 animals showed cochlear expression of the reporter gene, whereas all 8 animals showed strong lacZ expression in the middle ear mucosa, in the RWM and in the mucosa surrounding the stapes. CONCLUSION: Our results indicate that the RWM presents a close barrier, almost completely preventing the adenovirus to diffuse into the perilymphatic space. Therefore middle ear application of an adenoviral vector cannot be used to induce inner ear gene transfer. However, middle ear application of a viral vector may be useful for developing treatment for diseases of the middle ear mucosa.     

电离辐射对内耳的迟发性损害

To investigate the feature and mechanism of delayed effect of ionizing radiation on the inner ear, the function and structure of the inner ear of the guinea pigs were observed during 8 month's period after exposure to fractional doses of gamma radiation (2 Gy per day) with a total dose of 60 Gy. Morphological study was performed using light microscopy, transmission and scanning electron microscopy while the function was measured with electrocochleography (ECochG) and electronystagmography (ENG). The results showed that the mean CAP response threshold was 35.67 +/- 6.78 dB before radiation, and 41.17 +/- 7.76 dB, 47.00 +/- 8.82 dB and 71.00 +/- 7.63 dB at 1st day, 3rd month and 8th months after completion of treatment, respectively. No significant change was demonstrated in the auditory responses at the 1st day of radiation (P > 0.05), but there was obvious hearing loss at 3rd and 8th month (P < 0.01). The nystagmus duration induced by ice water (ENG) was 40.00 +/- 5.44 seconds before radiation, 22.71 +/- 7.93 seconds at 8th month after radiation (P < 0.01). Histologic examination at 8th month after radiation revealed atrophy and degeneration of stria vascularis, a reduced number of capillaries, degeneration of endotheliocyte in vessels, outer hair cell and supporting cell of Corti's organ. The percentage of damaged hair cells in basal turn of the cochlea was significantly higher than those of the upper turn. Degeneration of vestibular hair cell was found. It is suggested that radiation from routine radiotherapy doses may result in a delayed impairment of the inner ear. The main mechanism of the radiation damage may be interference of oxygen supply and metabolism of the inner ear by radiation vascular lesion.