Fatal tracheo-innominate artery fistula after tracheostomy in a patient with Pelizaeus-Merzbacher disease.

Tracheo-innominate artery fistula (TIF) is a serious, life-threatening complication following tracheostomy. We report a fatal TIF in a 15-year-old girl with Pelizaeus-Merzbacher disease. She received a tracheostomy for prolonged translaryngeal intubation due to acute respiratory failure without a trial of noninvasive ventilatory support before intubation. Severe hemorrhage from the TIF occurred 6 months after tracheostomy; immediate resuscitation failed. Antemortem fiberoptic bronchoscopy showed tracheal stenosis accompanied by granulation tissue, and postmortem examination revealed TIF with ulcerative granulation. Preventive intervention is required to avoid catastrophic TIF due to its high mortality rate. Moreover, to avoid prolonged translaryngeal intubation leading to tracheostomy, noninvasive ventilatory support before translaryngeal intubation, if applicable, is beneficial.

Bilateral progressive hearing loss and vestibular dysfunction with inner ear antibodies.

Autoimmune inner ear disease (AIED) is a clinical syndrome of uncertain etiology. We present the neuro-otological findings of 2 cases of bilateral hearing loss, dizziness and the antibody profiles of the inner ears. Case 1 had bilateral progressive hearing loss, vestibular dysfunction and abnormal eye movement as the disease progressed. She had inner ear antibodies against 42 and 58kDa protein antigency on Western blot immune assay, and responded to glycocorticosteroid but not to immunosuppressant treatment. Intratympanic steroid injection temporally eliminated her symptoms. However, she developed idiopathic Cushing's syndrome and underwent labyrinthectomy. Case 2 became deaf as a teenager and experienced dizziness 10 years after becoming deaf. He reacted strongly to 68kDa protein and was a good responder to immunosuppressant with steroid. As we still lack a definitive diagnostic test for AIED, careful observation of the clinical course is critical for differential diagnosis regarding the bilateral progressive hearing loss.

Expression of cochlin in the vestibular organ of rats.

The COCH gene mutated in autosomal dominant sensorineural deafness (DFNA9) encodes cochlin, a major constituent of the inner ear extracellular matrix. Cochlin constitutes 70% of the inner ear protein and cochlin isoforms can be classified into three subgroups, p63s, p44s and p40s. Symptoms of some DFNA9 patients are consistent with those of Ménière's disease. Here, we report the expression of cochlin in the vestibular organ of rats using isoform-specific antibodies that recognize all three isoforms. Cochlin is highly expressed in the stromata of the maculae of otolithic organs and cristae of semicircular canals, and in the channels in the bony labyrinth that transmit the dendritic innervation to the cristae and maculae. Cochlin cannot be detected in the sensory cells, dark cells, nor in the acellular structures, otolithic membrane or in the cupula. These findings support the theory that deposition of acidophilic substance in the inner ear caused by mutation of cochlin can induce a secondary retrograde dendritic degeneration of the vestibular nerves.

Interferon-gamma expression in the inner ear of rats following secondary immune reaction in the endolymphatic sac.

Recently, we demonstrated increased intercellular adhesion molecule-1 (ICAM-1) expression in the inner ear of systemically pre-sensitized rats after antigen [keyhole limpet hemocyanin (KLH)] challenge into the endolymphatic sac (ES), in good correlation with the cellular infiltration. Interferon-gamma (IFN-gamma) is an important cytokine that upregulates the expression of ICAM-1. Here, we report upregulation of IFN-gamma expression in the inner ear of systemically pre-sensitized rats after antigen (KLH) challenge into the ES. Immunoreactivity for IFN-gamma was detected in the spiral ligament, suprastrial region, spiral modiolar veins, spiral collecting venules, surface membrane of the perilymphatic compartment and perilymphatic space of immunized, but not control, rats. IFN-gamma expression was detected at 1.5 h post-challenge, peaked at 6 h and gradually returned to baseline levels after 7 days. Interestingly, the time kinetics of IFN-gamma expression were in good correlation with those of ICAM-1. These observations demonstrate that antigen challenge into the ES induces IFN-gamma expression, which can then upregulate ICAM-1 expression and induce cell infiltration, suggesting that IFN-gamma may play a crucial role in immune-mediated inner ear diseases.

[Immuno-pathogenesis in Meniere's disease].

Since the report of Duke in which an allergic etiology was considered to be the cause of Meniere's disease, the hypothesis that a certain type of Meniere's disease is generated through immuno-pathological mechanisms has been advocated for 70 years. During this period, another entity of immune-mediated inner ear disorders, i. e., autoimmune inner ear disease was introduced. Fundamental immunological phenomena of the inner ear have been rapidly elucidated since 1980. The endolymphatic sac is the only site which contains immuno-competent cells within the inner ear. The inner ear is capable of mounting active immune responses when appropriately stimulated and the endolymphatic sac plays an integral function for inner ear immune response. Actually, many reports have been published that link immunity and Meniere's disease with a variety of proposed immune-related etiologies from autoimmunity to non-autoimmunity. It is suggested that immune injury to the endolymphatic sac plays an important role in the pathogenesis of Meniere's disease. These functional and morphological circumstances strongly suggest that an immunological etiology of Meniere's disease is not theoretically unfounded.

Experimental autoimmune labyrinthitis: assessment of molecular size of autoantigens in fractions of inner ear proteins eluted on the Mini Whole Gel Eluter.

In order to determine the molecular size of the causative autoantigens of experimental autoimmune labyrinthitis, crude inner ear antigen was separated into 14 fractions and the constituent molecules were identified by means of sodium dodecyl sulfate-polyacrylamide gel electrophoresis using the Mini Whole Gel Eluter. The mean total protein recovery was approximately 66%. Sensitization with 55-65 kDa proteins induced the highest number of infiltrating cells among the fractions and sensitization with 38-45 kDa proteins induced the second highest number of inflammatory cells. These results suggest that 38-45 kDa and 55-65 kDa proteins are the causative autoantigens of experimental autoimmune labyrinthitis.

Expression of caspase-activated deoxyribonuclease (CAD) and caspase 3 (CPP32) in the hydropic cochlea of guinea pigs - second report.

Apoptosis was induced in the cochlea by the injection of keyhole limpet hemocyanin (KLH) into the endolymphatic sac of guinea pigs and immunohistochemically examined. Keyhole limpet hemocyanin was injected into the right endolymphatic sac. The temporal bones were fixed via cardiac infusion of fixative and immunohistochemically stained for caspase-activated deoxyribonuclease or caspase 3. Endolymphatic hydrops became evident in the cochlea 1 day after the injection of keyhole limpet hemocyanin (n=6). The temporal bones in the control group did not show any caspase-activated deoxyribonuclease or caspase 3 immunoreactivity (n=6). Immunoreactivity for caspase 3 was detected in the supporting cells of the organ of Corti, the stria vascularis and the spiral ganglion cells. Caspase-activated deoxyribonuclease was also detected in the same areas. These findings suggest that apoptosis is involved in the pathogenesis of endolymphatic hydrops. This phenomenon could lead to cochlear dysfunction, as seen in endolymphatic hydrops.

Local injection of OK-432 in the treatment of ranula: a case report.

We treated a 57-year-old woman for ranula. After aspirating the cyst's contents, we administered 0.1 KE/ml of OK-432 via local injection. One month later, the cyst had still persisted, so we repeated the procedure. After 2 weeks, the ranula began to shrink markedly, and at 4 weeks it had almost disappeared. No recurrence of the ranula was observed during the subsequent 1 year of follow-up. Following each injection, the patient developed transient fever and local swelling but no serious complications. Our experience suggests that OK-432 injection is an effective treatment for ranula. However, because this treatment causes the cyst to collapse rather than disappear completely, patients should be regularly monitored over the long term.