Shigeru Inafuku

A Quantitative Analysis of Cedar Pollen-Specific Immunoglobulins in Nasal Lavage Supported the Local Production of Specific IgE, Not of Specific IgG

Many studies have proved the relevance of local immune responses, rather than systemic immunity, to the pathogenesis of allergic rhinitis. Indeed, allergen‐specific B lymphocyte undergoes class switching to IgE in situ. However, the relative contribution of in situ production to the amount in serum is still ambiguous. Here, a quantitative comparison of the local concentration of allergen‐specific IgE with the systemic concentration was explored for the estimation. Among seasonal rhinitis patients, total and Japanese cedar pollen (JCP)‐specific IgE, IgA and IgG antibodies were quantified in nasal lavage fluid (NLF) and serum with the time‐resolved fluorescence immunosorbent assay. Although the total amounts of IgE and IgG classes in the NLF, which were apparently passive discharge from the mucosal tissue, were smaller and variable, the relative proportions of JCP‐specific antibodies could be quantitatively compared between NLF and serum or between subjects. The proportions of specific IgE in the NLF were remarkably higher than in serum (average 13.2‐fold) in most subjects, which strongly supported the predominant in situ production of the specific IgE and subsequent dilutions in the systemic circulations. Similar but smaller values were obtained for IgA (average 3.7‐fold). In contrast, the specific proportions of IgG in the NLF were surprisingly consistent with serum (average 1.0‐fold), suggesting that the specific IgG was mostly produced in the downstream lymphoid organs. The local productions of specific IgE would encourage the topical therapies and the usage of the NLF for the diagnosis of allergic rhinitis.

Differential diagnosis of obstructive sleep apnea syndrome patients and snorers using cephalograms

Abstract Severe snoring is thought by many to be an early stage of obstructive sleep apnea syndrome (OSAS), but the anatomical relation between snoring and OSAS, if any, has remained unclear. To compare the morphology of the airway between snorers and OSAS patients for possible similarities, we conducted a cephalometric analysis of Japanese OSAS patients (n = 10), habitual snorers (n = 10), and non‐snoring controls (n = 50). There was no significant difference in SNB (the angle formed by the sella, nasion and point B) between OSAS patients and the control subjects. Obstructive sleep apnea syndrome patients tended to have an anteriorly positioned maxilla, and an anteroposterior misalignment between the maxilla and mandible. There was also a tendency toward skeletal openbite. Both OSAS patients and snorers had large tongues and large soft palates, thus causing constriction of the airway with resultant smaller airway diameter and smaller airway surface area. Significant differences between OSAS patients and snorers were found in thickness and length of soft palate surface area, and thickness, length, and position of the hyoid bone. These results suggest that cephalographic measurements may be of considerable use in determining the seriousness of a patients condition.

Effects of MRI contrast agents (Omniscan™) on vestibular end organs

Conclusion: These findings indicate that application of 4–16-fold diluted Omniscan™ could have depressant effects on the frog vestibular end organs. Based on cochlear studies on cytotoxicity using 8-fold diluted Omniscan, 16-fold diluted Omniscan is optimal for the inner ear and its application could be useful for visualization of endolymphatic hydrops as well as the control of vertiginous attacks in Menieres disease. Objectives: Endolymphatic hydrops could be visualized recently by intratympanic injection of Omniscan diluted 8- or 16-fold with saline using three-dimensional fluid attenuated inversion recovery (3-D FLAIR) MRI. However, the effects of the Omniscan on vestibular end organs are not clearly understood. The purpose of this study was to investigate the effects of Omniscan on vestibular end organs both morphologically and physiologically. Materials and methods: Vestibular hair cells isolated from bullfrogs were loaded with 4–32-fold diluted Omniscan (gadolinium hydrate) and morphological changes were observed. Moreover, compound action potentials of posterior semicircular canals were also observed after application of Omniscan. Results: Application of 4–16-fold diluted Omniscan caused morphological damage of isolated vestibular hair cells and decreased action potentials of the posterior semicircular canal. After application of 32-fold diluted Omniscan, no apparent changes were noted even after 20 min, both morphologically and physiologically.

Effects of hydrogen peroxide on vestibular hair cells in the guinea pig: importance of cell membrane impairment preceding cell death

Conclusion. Our findings indicate that oxidative stress induces morphological changes in vestibular hair cells and subsequently leads to cell death after 2.5 h. Objectives. The aim of this study was to confirm the direct effects of oxidative stress on vestibular hair cells. Materials and methods. Vestibular hair cells isolated from guinea pigs were loaded with 1 or 10 mM H2O2, and morphological changes were observed. In addition, in a viability/cytotoxicity assay system, the numbers of dead cells in isolated cristae ampullares were counted 1, 3, and 5 h after loading with H2O2 or artificial perilymph (control). Results. Reactive oxygen, in the form of H2O2, directly affects the cell membrane of isolated vestibular hair cells and causes swelling of the cell body, bleb formation, and shortening of the neck region. Morphological changes occur within 30 min after loading with H2O2, but a significant increase in the number of dead cells is noted only after 3 h.

Use of trafermin to treat a skin ulcer after repair of a deep auricular laceration: A case report

We used trafermin (recombinant human basic fibroblast growth factor) to treat a skin ulcer (diameter, 1 cm; depth, 2 mm) that developed after an extremely deep auricular laceration was sutured. Excellent results were obtained after use of trafermin for 2 weeks. To our knowledge, we report the first clinical use of trafermin in a patient with a skin ulcer resulting from auricular trauma. Trafermin may promise to be an effective treatment for skin ulcers.

In Reference to Visualization of Endolymphatic Hydrops in Patients With Meniere's Disease

We read with great interest the paper by Dr. Tsutomu Nakashima et al.1 entitled “Visualization of Endolymphatic Hydrops in Patients With Meniere’s Disease.” The authors could visualize endolymphatic hydrops by intratympanically injecting the test solution (gadolinium hydrate diluted 8-fold with saline) and using three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging. However, the influence of test solution on inner ear cells is not clearly understood. The test solution might not enter all parts of the inner ear because the osmotic pressure of the endolymph increases in patients with Meniere’s disease. However, it is risky to inject test solution intratympanically in patients with sudden deafness (especially patient 8). We measured osmotic pressure of the test solution with an advanced micro-osmometer (Osmostat OM-6040, Arkray, Inc., Kyoto, Japan) and showed it to be 324 to 325 mOsm. The test solution was hypertonic to the osmotic pressure of the endolymph (300–310 mOsm) and perilymph (300 mOsm).2,3 For these reasons, the high osmotic pressure4 of Nakashima et al.’s test solution could result in extensive apoptosis in inner ear hair cells. In fact, our preliminary experiments demonstrated shortening of the isolated cochlear outer hair cells 30 minutes after exposure to Nakashima et al.’s test solution. Moreover, the cells demonstrated shrinking and ballooning after 60 minutes. All cells exposed to Hanks’ Balanced Salt Solution (adjusted to 300 mOsm by HEPES) remained morphologically normal for at least 2 hours. Isolated vestibular hair cell shape changes were shown after exposure to hypotonic (280–90 mOsm) solutions.3 Zou et al.5 suggested that the potential for osmotic damage may exist if the test solution is not osmotically balanced. Therefore, it is important to adjust the osmotic pressure of the test solution to 300 mOsm. Recently, the U.S. Food and Drug Administration warned that a serious late adverse reaction called nephrogenic systemic fibrosis may occur after exposure to the gadolinium-based contrast medium.6 These conditions may result from the accumulation of gadolinium ions in several organs. The gadolinium ions do not usually separate from the contrast medium because of the chelations. However, if they should separate inside the inner ear, the inner ear cells could be oxidized.7 The gadolinium ions also could inhibit the volume regulation8 and mechanotransduction systems9 of the hair cells and could even be involved in irreversible inner ear dysfunction. We believe that the trial by Nakashima et al. is clinically significant. It is necessary to check the safety of their test solution for every cell inside the inner ear and confirm it immediately with in vivo animal experiments.

Five cases of chondroma involving the external auditory canal

A cartilaginous tumor located in the external auditory canal is a rare finding. Only 48 cases of chondromas of the external auditory canal have been documented in the literature. The natural course of these tumors as well as the diagnosis and management has not been well established. We have encountered five cases of external auditory canal chondroma. The patients consisted of three males, ages 12, 14, and 29, and two females, ages 2 and 3, respectively. Otoscopic examination demonstrated a tiny firm tumor protruding from the anterior wall of the bony external auditory canal. Surgery was performed all cases, and the tumor proved to be a chondroma histologically. All cases could be approached through the ear canal. The postoperative courses were uneventful and no recurrences were found during the follow-up periods. From our experiences, it is important to recognize that chondromas are in the differential of small exophytic tumors on the anterior or superior wall of the external auditory canal and can be removed safely and effectively through the transcanal approach.

A case of polyradiculitis with hearing loss: analysis of auditory brain stem response.

A case of acute polyradiculoneuritis accompanied by rare complications of the VII, VIII and IX cranial nerve disorder was described. There was an elevation of the rubella virus antibody titer, which suggested the case had been infected before. Thirty-eight year-old woman complained of bilateral tinnitus and was proven audiometrically to have sensori-neural hearing loss. Electroacoustical examination disclosed that all the waves were suppressed and that wave I and V were barely detected, while wave II, III and IV were absent. The neurological and audiological disorders were successfully treated with corticosteroid, and the patient had neither sequelae nor recurrence.

Nasal hemangiopericytoma successfully treated with a combination of rIL-2 and extranasal approaches

Abstract Hemangiopericytomas (HPCs) are uncommon vascular tumors originating from extracapillary cells called pericytes, and rarely occur in the nose or paranasal sinuses. We treated a 57-year-old man with nasal HPC who presented with nasal obstruction and hemorrhage. Nasal endoscopy showed a readily bleeding mass between the right nasal septum and inferior turbinate. Enhanced CT revealed a heterogeneous mass lesion with an enhancement effect that filled the right nasal cavity. A biopsy specimen was proved to exhibit a HPC histopathology. Recombinant interleukin-2 (rIL-2) was administered with a measurement of natural killer cell (NK cell) activity. Afterwards, wide excision with an extranasal approach was performed. The use of rIL-2 caused not only increased NK cell activity but also a reduction in the tumor size. With a combination of rIL-2 and wide excision with extranasal approaches, no local recurrence or metastasis has occurred over the last 4 years.

Effects of Dexamethasone on Tissue Injury and Reconstruction in Ethanol/Steroid Injection Therapy for Allergic Rhinitis

Conventional therapies involving radiofrequency tissue ablation or laser cauterization for allergic rhinitis are accompanied by lesioning and restoration of the mucosa, which are important healing processes. The extent of these processes is difficult to control in these therapies, however, and often leads to mucosal erosion and severe pain for patients. To address this problem, we attempted to develop a new clinical treatment for allergic rhinitis that mitigates requisite mucosal damage through the injection of ethanol (E) containing a glucocorticoid into the inferior turbinate mucosa in taking advantage of the superior degeneration and coagulation capabilities of E in tissues [1,2]. We predicted that considerable technical skill would be required to inject ethanol into the nasal mucosa without spreading tissue damage to the mucosal surface. We overcame this technical problem by alleviating tissue damage as much as possible in the early treatment phase after the injection because injury is augmented by an inflammatory response characterized by neutrophil infiltration that accompanies tissue damage upon ethanol administration [3]. In doing so, we found that adding a glucocorticoid with potent anti-inflammatory activity alleviated tissue damage and by preserving the contractile effects of tissue itself, reduced the infiltration of inflammatory cells, especially neutrophils, into inflamed sites in a dose-dependent manner [3]. The clinical application of this E/steroid mixture as so-called submucosal E/steroid injection