Published papers

Introduction: During the acute phase, patients with vestibular neuritis suffer from severe vertigo. With time, the intensity of vertigo gradually decreases. The aims of the present study were: (1) to determine whether changes in the subjective visual vertical (SVV) system reflect how patients subjectively experience vertigo, and (2) to determine the relationship between changes in SVV and canal paralysis (CP). Methods: Our subjects comprised 23 patients with vestibular neuritis. We measured the SVV of each patient several times to evaluate the recovery of SVV and CP over time. The intensity of vertigo was graded numerically as follows: (1) 5 - very intense (patient cannot stand with eyes open), (2) 4 - intense (patient cannot stand with eyes closed), (3) 3 - moderate (patient can stand with eyes closed), (4) 2 - slight vertigo, and (5) 1 - no vertigo. We also evaluated CP in 10 patients using the thermal caloric test. Results: The temporal process of SVV recovery was grouped into three categories: (1) small fluctuation/rapid recovery (N=7); (2) small fluctuation/delayed recovery (N=8); and (3) large fluctuation (N=8). For CP recovery, we observed cases that failed to recover (N=4) and others that did recover (N=6). When tested 30 days and 1 year after the initial examination, the CP recovery group displayed larger SVV fluctuations accompanied by intense subjective vertigo, whereas the group that did not recover exhibited fewer fluctuations accompanied by weak vertigo. Conclusions: SVV represents the subjective perception of the direction of gravity. Fluctuations in SVV, rather than absolute SVV, correlate well with the subjective intensity of vertigo. This suggests that, during the recovery process, fluctuations in SVV, rather than the dysfunction itself, causes dizziness. Measuring SVV is very straightforward and quantifying SVV fluctuations is an effective measure of the intensity of vertigo.

PURPOSE OF THE REPORT: Although salivary gland scintigraphy has been useful for the diagnosis of Warthin's tumor (WT), there are no reports concerning the clinical impact of this scintigraphy. MATERIALS AND METHODS: We retrospectively investigated 127 patients with solitary parotid tumors who had undergone salivary gland scintigraphy. RESULTS: For patients who had surgery, the sensitivity, specificity, and accuracy of differentiating WT from non-WTs were 95%, 91%, and 92%, respectively. There was a significant correlation between scintigraphic results and the treatment decisions made for the 127 patients (χ = 16.5, P = 0.00026). The proportion of WT patients among those who underwent surgery was 19%, whereas 42% of those who were suspected to have WT from scintigraphy were followed without surgical intervention. The main reasons for clinical observation in these patients were comorbidity, refusal of surgery, and age. CONCLUSIONS: The high percentage of nonsurgical patients suspected to have WT can be explained by the high diagnostic accuracy of salivary gland scintigraphy, which is useful for determining further management when surgery is contraindicated or is refused by the patient.

To define the role of free radical formation and potential energy depletion in noise induced hearing loss (NIHL), we measured the effectiveness of tempol (free radical scavenger) and creatine (enhances cellular energy storage) alone and in combination to attenuate NIHL. Guinea pigs were divided into four treatment groups: controls, 3% creatine diet (2 weeks prior to noise exposure), tempol (3 mM in drinking water 2 weeks prior to exposure), and creatine plus tempol and exposed to 120 dB SPL one-octave band noise centered at 4 kHz for 5 h. The noise-only control group showed frequency-dependent auditory threshold shifts (measured by auditory brainstem response, ABR) of up to 73 dB (16 kHz) on day 1, and up to 50 dB (8 kHz) on day 10. Creatine-treated subjects had significantly smaller ABR threshold shifts on day 1 and on day 10. Tempol alone significantly reduced ABR threshold shifts on day 10 but not on day 1. ABR shifts after combination treatment were similar to those in the creatine group. Hair cell loss on day 10 was equally attenuated by creatine and tempol alone or in combination. Our results indicate that the maintenance of ATP levels is important in attenuating both temporary and permanent NIHL, while the scavenging of free radicals provides protection from permanent NIHL.

Introduction: Using the near-infrared spectroscopy (NIRS), we evaluated the central circulation of patients with either dizziness and orthostatic dysfunction or dizziness alone. Methods: We used the NIRO-200 NIRS instrument to monitor bilateral oxygenation changes in cerebellar hemoglobin levels in 57 subjects during an orthostatic exam. Of the 46 patients with dizziness, 8 had orthostatic dysfunction. To determine whether NIRS is useful for evaluating patients with dizziness, we compared blood pressure changes with orthostatic dysfunction test scores. Diagnostic criteria for orthostatic dysfunction were as follows: (1) a greater than 21 mmHg reduction in systemic blood pressure, (2) a greater than 16 mmHg reduction in pulse pressure, and (3) a greater than 21 beats per minute increase in pulse rate. Results: We observed four different types of changes in oxy-hemoglobin during the orthostatic test. In type I, a rapid temporal decline of oxy-hemoglobin was followed by rapid recovery. In type II, the decline of oxy-hemoglobin was followed by recovery of oxy-hemoglobin levels above the initial levels. In type III, the decline of oxy-hemoglobin was followed by recovery of oxy-hemoglobin levels below the initial levels. In type IV, the decline of oxy-hemoglobin persisted without recovery. Most of the control patients displayed type I changes. Patients with orthostatic hypertension more frequently displayed type II and IV changes. Nine of the dizzy patients had a positive orthostatic test. Of these patients, 3 displayed type II changes and 6 displayed type IV changes. Conclusions: In normal subjects, cerebellar circulation remains stable, at least if orthostatically induced changes in blood pressure remain within normal ranges due to autoregulation. We suspect that dysfunctional autoregulation was responsible for the reduced cerebellar circulation in patients with orthostatic dysfunction. We propose that NIRS is an excellent, non-invasive tool for evaluating patients with dizziness that present with orthostatic dysfunction.

Introduction: For the repair of large orbital floor defects due to blow-out fractures or those involved by tumours, it is necessary to understand the detailed morphology. The purpose of the present study was to elucidate how age and gender affect its three-dimensional morphology. Methods: The 3-D computer tomography data of 305 orbits of 182 patients were included in the study. Using the CT data, the orbital floor angle (the angle between the orbital floor and the horizontal plane) and the location of the most inferior point of the orbital floor were measured. Patients were classified into subgroups according to their gender and age. Data were compared among the subgroups. Results: The orbital floor angle was greater in males than in females, and in children than in adults. The location of the lowest point of the orbital floor moves postero-inferiorly with increasing age. Conclusion: The present study demonstrated that gender and age affects morphology of the orbital floor. These findings should be useful for reconstruction of the orbital floor.

We report a unique case of cholesterol granuloma (CG) surrounding the endolymphatic sac (ES). A 49-year-old man presented with the left side of sensorineural hearing loss, tinnitus, and vertigo. Magnetic resonance and computed tomography imaging revealed a CG surrounding the left ES. The patient initially underwent left transmastoid surgical resection of the tumor. At the time of surgery, brown fluid was aspirated from the tumor, but no other tumors were found. Histopathological examination revealed that the tumor contained cholesterol crystals, confirming the diagnosis of CG. At his 12-month postoperative follow-up, there was no evidence of recurrence. We discuss the radiology, pathology, and surgical removal of CGs surrounding ES.

Small oropharyngeal carcinomas with advanced neck metastases (stage N2 or greater) are common. Patients with small T with large N oropharyngeal carcinoma have high rates of local control but lower rates of regional control when treated with chemoradiotherapy. Clinical assessment after chemoradiotherapy cannot ensure the absence of neck disease. In the last 5 years, we have treated patients with T1-2 with N2-3 oropharyngeal carcinoma with weekly docetaxel radiotherapy followed by planned neck dissection (PND). Our objectives were to clarify the pathologically complete response (CR) rate of neck metastasis after weekly docetaxel radiotherapy, to identify the clinical predictor of residual neck disease, and to determine the mobidity of planned neck dissection. After chemoradiotherapy, all 12 patients had a complete response at the primary site. We conducted 15 neck dissections. Of these, 6 (40%) had positive nodes. The pathological CR rate of neck metastasis was 58.3%, whereas overall 2-year neck control rate was 91.7%. These findings lend support to the role of PND after chemoradiotherapy in N2-3 neck disease. After chemoradiotherapy, clinical parameters including TN status, feasibility of chemoradiotherapy, largest lymph node size or size reduction in MRI, did not identify patients with residual neck disease. We conducted selective neck dissection (SND) in 80% of patients. SND as PND appears to be appropriate in this group of patients because of the low incidence of complications. A further cohort study including the comparison of PND nonenforcement group is necessary to clarify the validity of the addition of PND in weekly docetaxel radiotherapy.

We injected a recombinant Sendai virus (SeV) vector into the guinea pig cochlea using two different approaches - the scala media and scala tympani - and investigated which cell types took up the vector. The hearing threshold shift and distribution of transfected cells in animals using the scala media approach were different compared to those using the scala tympani approach. SeV can transfect very different types of cells, including stria vascularis, spiral ganglion neurons, and sensory epithelia of the organ of Corti, and fibrocytes of the scala tympani. Because SeV vectors can potentially deliver stimuli to the cochlea to induce hair cell regeneration, it may be a powerful tool for repairing the organ of Corti.

Glossopharyngeal nerve paralysis caused by varicella zoster virus reactivation is rare. We present a case of glossopharyngeal zoster confirmed by direct immunofluorescence staining for virus antigens. A 35-year-old man presented with right-sided, severe swallowing pain and dysgeusia. Physical examination showed a loss of ipsilateral gag reflex. White spots on the posterior wall of the right pyriform sinus were seen by laryngofibroscopy, and a loss of taste on the right posterior part of the tongue was confirmed by gustometry using the filter paper disc method. The varicella zoster virus antigen was revealed by direct immunofluorescence staining by fluorescein isothiocyanate labelled mouse monoclonal antibody specific for varicella zoster virus glycoprotein, using samples obtained from the mucosal lesion by abrasion with a cotton swab. The patient was treated by intravenous administration of acyclovir. His throat pain and dysgeusia completely resolved. We discuss the advantages of direct immunofluorescence staining for varicella zoster virus antigen for the diagnosis of glossopharyngeal zoster.

Objective: Although first line therapy of sleep-disordered breathing (SDB) in children is adeno-tonsillectomy, the indications for this operation have not yet been clearly established. We investigated whether pulse-oximetry is useful for determining the optional treatment modality for pediatric SDB. Method: Two hundred and thirty-two children presenting with snoring and gasping had their oxygen saturation levels examined during sleep. Among them, 86 underwent on adeno-tonsillectomy and were evaluated pre- and post-surgery. We also examined 25 healthy children as controls. Results: Little desaturation was observed in healthy children. The difference in oxygen saturation levels of the patients between pre- and post-surgery was closely correlated with the pre-surgery levels. We examined the reaction operation characteristics and concluded that children with an oxygen desaturation index of 4% or more (ODI4) of more than 1.5 and/or ODI3 of more than 3.5 should undergo surgery. Conclusion: Pulse-oximetry is useful in determining the indications for adeno-tonsillectomy.

We report on 2 cases of hypothyroidism presenting clinical symptoms that occurred after radiotherapy for cancer of the head and neck and on the results of estimating thyroid function in patients with head and neck cancer who received radiotherapy. The first patient underwent total laryngectomy for laryngeal cancer without sacrificing the thyroid gland and partial gastrectomy for gastric cancer. Radiotherapy of the neck was carried out postoperatively. Two years later, the patient developed chest pain; pericardial effusion was detected, leading to a diagnosis of myxedema caused by hypothyroidism. The second patient received radiotherapy alone for laryngeal cancer. Two months later, low serum sodium concentration and anemia were detected in this patient. The cause of these changes was subsequently found to be hypothyroidism. Based on our experience with these 2 cases, we measured thyroid function in 35 patients who had undergone neck radiation for head and neck cancer at our hospital over the past 10 years. Hypothyroidism was observed in 13 of the 35 patients (37%). The prevalence of hypothyroidism was 46% (6/13) for patients treated with both radiation and surgery, as compared with 32% (7/22) for those who received radiation alone. The risk factors responsible for hypothyroidism were not evident from the statistical analysis of these cases. We believe that thyroid function should be evaluated periodically in patients who have undergone neck radiation because it is often difficult to diagnose hypothyroidism only from clinical symptoms.

Despite its rarity, information on the diagnosis of parapharyngeal space tumors such as through imaging and aspiration biopsy cytology, is slowly accumulating. Little detailed examination has been conducted, however, on surgical approach, complications, and sequelae. We report the results of a retrospective review of 27 patients with primary parapharyngeal space tumors-25 with benign disease and 2 with malignant lesions-treated surgically. Surgical approach, postoperative complications, sequelae, and operative indications of parapharyngeal space tumors were examined in 28 operations on the 27 patients. Tumors found in the prestyloid region in CT or MRI are treated as salivary gland or malignant tumors. Those found in the poststyloid region are treated as shwannoma or paraganglioma. The transcervical approach is often used in patients with shwannoma, while a variety of approaches are selected for patients with salivary gland tumors. Complications occur in 50% of patients, however, bias based on pathological diagnosis has not been examined to the degree needed. Sequelae in our series occurred in 46.4% of our patients. Sequela in the patients with shwannoma, however, is 81.8%, compared to 9.1% in patients with salivary gland tumors. Prestyloid parapharyngeal space tumors seem to be "automatically" indicated for surgery, because the surgical risk is lower than the risk of inaction. In poststyloid parapharyngeal space tumors, however, it appears necessary to judge indication for surgery more carefully while considering the social background, age, and occupation of prospective surgical candidates.

We reviewed 11 patients (7 women and 4 men) with acquired dacryostenosis who underwent a dacryo-cysto-rhinostomy (DCR) at Saiseikai Utsunomiya Hospital between May 2000 and April 2004. The etiology was considered chronic inflammation in six, trauma in two and complications of paranasal sinus surgery in two. In addition to lacrymal probing and irrigation, we investigated all patients by anterior rhinoscopy and CT. One patient showed pneumatization in the lacrymal sac on CT and dacryoatresia was confirmed with irrigation. We diagnosed the common canaliculi as the site of atresia, and this was confirmed intraoperatively. We treated 7 cases by traditional extenal DCR (EXT-DCR) and 4 by endonasal endoscopic DCR (EE-DCR). We treated one case of relapsed obstruction with EE-DCR but treated well with the same method. The EXT-DCR cases have not show any recurrence to date. There were two cases of stenosis at the common canaliculi and both were improved after EE-DCR with silicone tube insertion. With EE-DCR, the duration of surgery was shorter and there was no scar formation or facial deformity. We suggest that ENT doctors should pay more attention to diseases of the naso-lacrymal system and cooperate with ophthalmologist when designing treatment regimens.

Bones conduct sound in the middle ear. The three ossicles-the malleus, incus, and stapes-form a chain that transmits vibrations from the tympanic membrane to the oval window of the inner ear. Little is known about bone remodeling events in these ossicles and about potential effects of osteoporosis on hearing loss. Osteoclastic bone resorption is enhanced in Opg-/- mice lacking osteoprotegerin, which is a soluble decoy receptor for the osteoclastogenic cytokine RANKL. We asked whether auditory ossicles are resorbed in Opg-/- mice, and whether these mice suffer from impaired auditory function. All three ossicles in Opg-/- mice showed thinning, especially at the malleal manubrium and incus body. Most notably, unlike in the case in wild-type mice, the junction between the stapes and the otic capsule was fixed in Opg-/- mice, and the stapedial footplate was thinner and broader. Radiological analyses revealed that malleal cortical thickness was positively correlated with tibial bone mineral density in Opg-/- and control littermate mice. Furthermore, progressive hearing loss was detected in Opg-/- mice starting at 6 to 15 weeks of age. These data suggest that osteoprotegerin plays a crucial role in hearing by protecting the auditory ossicles and otic capsule from osteoclastic bone resorption.

Total laryngectomy or laryngopharyngectomy are commonly performed for the treatment of laryngeal cancer or hypopharyngeal cancer. However pharyngocutaneous fistula and cervical esophageal stenosis have been reported as postoperative complications of these procedures. We used a silicon pharyngeal tube in cases that developed pharyngocutaneous fistula and cervical esophageal stenosis. The pharyngeal tube was useful for controlling aspiration pneumonia and for starting oral feeding in a case of pharyngocutaneous fistula after a total laryngectomy. It was also helpful for starting oral feeding in a case with cervical esophageal stenosis after total laryngopharyngectomy and free jejunum interposition. This patient was able to maintain a good quality of life until re-operation. Adverse effects from the insertion of the tube included a foreign body sensation and pharyngeal pain that was tolerable with the use of NSAIDs for a short time. Silicon pharyngeal tubes are useful for the treatment of pharyngocutaneous fistula and cervical esophageal stenosis.

Calcium phosphate cement (CPC) consists of powder and liquid, which become an injectable paste after mixing, self-hardening and recrystallizing to calcium hydroxylapatite (CaHA) after injection into a living body. In this study, we investigated the suitability of CPC as an injectable material for injection laryngoplasty using rabbits. All rabbits underwent left recurrent laryngeal nerve section and injection laryngoplasty with CPC. At 7 days, scanning electron microscopic findings revealed that complete recrystallization from CPC to CaHA was achieved in the larynx. At 1, 3, and 6 months, injected CPC stayed in the paraglottic space and did not migrate, and the average remaining CPC volume percentage was 91.7%. Focal foreign body reaction to injected CPC was almost the same as that of autologous fat for all time periods observed. These results indicated that CPC appears to be biocompatible, nonabsorbable, nonmigratory, and suitable for injection laryngoplasty.

Recent studies have showed that inflammatory responses occur in inner ear under various damaging conditions including noise-overstimulation. We evaluated the time-dependent expression of proinflammatory cytokines in noise-exposed rat cochlea. Among several detected cytokines, real-time RT-PCR showed that interleukin-1beta (IL-1β) and interleukin-6 (IL-6) were significantly induced 3 hr after noise exposure, and quickly downregulated to the basal level. Tumor necrosis factor-alpha (TNF-α) was also slightly upregulated immediately after noise exposure, Immunohistochemical analysis showed that IL-6 expression was distinctively induced within the lateral side of the spiral ligament. Sequential expression analysis showed that IL-6 immunoreactivity was initially found in the cytoplasm of lateral wall cells, including Type IV and III fibrocytes, and expanded broader throughout the lateral wall, finally to the stria vascularis. Because of the negative Iba-1 staining, IL-6 expression in the early-phase was not due to macrophage or microglia activation. IL-6 was also detected in spiral ganglion neurons at 12 and 24 hr after noise exposure. Our data demonstrates the production of proinflammatory cytokines, including TNF-α, IL-1β, and IL-6, in early phase of noise overstimulated cochlea. IL-6 expression was observed in the spiral ligament, stria vascularis, and spiral ganglion neurons. These cytokines, produced by the cochlear structure itself in response to noise exposure, may initiate an inflammatory response and have some role in the mechanism of noise-induced cochlear damage.

We have previously shown that neuroprotective effects of an adenoviral glial cell line-derived neurotrophic factor (GDNF) gene transfer on the lesioned adult rat motoneurons in the nucleus ambiguus. In the present study, we examined neuroprotective effects of adenoviral gene transfer of brain-derived neurotrophic factor (BDNF) or/and GDNF to motoneurons in nucleus ambiguus using an adult rat vagal nerve avulsion model. The animals avulsed and inoculated with adenoviral vectors encoding BDNF (AxCAmBDNFME) or/and GDNF (AxCAhGDNF) showed immunolabeling for BDNF or/and GDNF in the nucleus ambiguus on the treated side, respectively, and expression of virus-induced BDNF or/and GDNF mRNA transcripts in the brainstem tissue that contained the nucleus ambiguus of the treated side. The treatment with AxCAhGDNF or AxCAmBDNFME significantly prevented the loss of vagal motoneurons in comparison to the control; the protective effect of AxCAmBDNFME was greater than that of AxCAhGDNF. The combined treatment with AxCAmBDNFME and AxCAhGDNF acted synergistically and significantly larger number of vagal motoneurons was preserved as compared to either AxCAmBDNFME treatment or AxCAhGDNF treatment. The treatment with AxCAmBDNFME or/and AxCAhGDNF after avulsion also suppressed the activity of nitric oxide synthase in lesioned motoneurons in the nucleus ambiguus. These results indicate that adenovirus-mediated BDNF and GDNF gene transfer may prevent the degeneration of motoneurons in humans after either vagal nerve injury or recurrent laryngeal nerve injury.

To assess the possibility of gene therapy for recurrent laryngeal nerve (RLN) injury, we examined functional and histological recovery after glial cell line-derived neurotrophic factor (GDNF) gene transfer in a rat RLN crush model. Adenoviral vector encoding β-galactosidase gene (AxCALacZ) or human GDNF gene (AxCAhGDNF) was injected into the crush site of the RLN. Neurons in the nucleus ambiguus on the crushed side were labeled with X-gal or GDNF immnohistochemistry after AxCALacZ or AxCAhGDNF injection. Reverse transcription-polymerase chain reaction analysis revealed expression of human GDNF mRNA transcripts in brainstem tissue containing the nucleus ambiguus on the crushed side after AxCAhGDNF injection. Animals injected with AxCAhGDNF displayed significantly improved motor nerve conduction velocity of the RLN and recovery rate of vocal fold movement at 2 and 4 weeks after treatment as compared to controls. AxCAhGDNF-injected animals showed a significantly larger axonal diameter and improved remyelination in crushed RLN as compared to controls. Adenoviral GDNF gene transfer may thus promote laryngeal function recovery after RLN injury. Inoculation of adenoviral vector containing the GDNF gene at the site of damage soon after nerve injury may assist patients with laryngeal paralysis caused by nerve injury during head and neck surgery.

Recently, vertigo or dizziness has been linked to abnormal serotonin regulation in the hippocampus. According to the DSM-VI and ICD-10, vertigo or dizziness is a common symptom of anxiety disorder, somatoform disorder, and depression. In today's stressful society, we are now observing record increases in the number of patients with depression. Because of this increase, otolaryngologists are now encountering an increasing number of patients with depression-related dizziness or vertigo. We treated 41 patients with depression-related vertigo or dizziness with a selective serotonin reuptake inhibitor (SSRI: paroxetine or fluvoxamine) or a selective norepinephrine reuptake inhibitor (SNRI: milnacipran). We graded the effects of treatment according to three levels: outstanding, effective, or not effective. Besides dizziness, the chief complaints of patients we treated were problems with sleep, headache, heavy headedness, shoulder stiffness, and loss of motivation. Drug effectiveness or the overall recovery rate was defined as the ratio of the number of patients showing outstanding and effective improvements to the total number of patients treated with a particular drug. The overall recovery rate for patients treated with paroxetine was 82% (14/17), for patients treated with fluvoxamine it was 90% (10/11), and for patients treated with milnacipran it was 62% (8/13). Side effects were observed in 22% (9/41) of the patients. Symptoms disappeared in about 2 weeks after drug treatment began. SSRIs and SNRIs are now the drugs-of-choice for treating anxiety- or depression-related vertigo because they are associated with fewer adverse effects than traditional antidepressants. Moreover, when compared to tranquilizers, SSRIs and SNRIs tend to be less habit-forming. As an adjunct to psychological counseling, dizziness associated with psychiatric disorders can also be treated in otolaryngological outpatient clinics with relevant drugs. To effectively treat these dizzy patients, collaboration between the patients' otolaryngologists and psychiatrists or psychological counselors is also important.