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Cerebral venous thrombosis as a manifestation of paraneoplastic angitis and otitis media, revealing non-Hodgkin B-cell lymphoma (NHBL), is extremely rare. A 57-year-old woman presented with headache, auditory disturbance and recalcitrant otitis media. Magnetic resonance imaging showed brain edema in the temporal lobe and transverse sinus thrombosis. External drainage under antibiotic treatment was repeated based on a diagnosis of invasive otitis media and mastoiditis associated with infectious sinus thrombosis, but the condition deteriorated progressively. Open surgery for otitis media was performed 6 years after the initial symptoms and after a tumorous lesion had been detected in the middle ear. Pathological findings revealed NHBL. We report a rare case of NHBL presenting as otitis media and mastoiditis associated with sinus thrombosis, and a literature review.

Mutations in SLC26A4 cause a broad phenotypic spectrum, from typical Pendred syndrome to nonsyndromic hearing loss associated with enlarged vestibular aqueduct. Identification of these mutations is important for accurate diagnosis, proper medical management and appropriate genetic counseling and requires updated information regarding spectrum, clinical characteristics and genotype-phenotype correlations, based on a large cohort. In 100 patients with bilateral enlarged vestibular aqueduct among 1511 Japanese hearing loss probands registered in our gene bank, goiter data were available for 79, of whom 15 had Pendred syndrome and 64 had nonsyndromic hearing loss. We clarified the mutation spectrum for the SLC26A4 mutations and also summarized hearing levels, progression, fluctuation and existence of genotype-phenotype correlation. SLC26A4 mutations were identified in 82 of the 100 patients (82.0%). Of the Pendred syndrome patients, 93% (14/15) were carriers, as were 77% (49/64) of the nonsyndromic hearing loss patients. Clinical characteristics of patients with SLC26A4 mutations were congenital, fluctuating and progressive hearing loss usually associated with vertigo and/or goiter. We found no genotype-phenotype correlations, indicating that, unlike in the case of GJB2 mutations, the phenotype cannot be predicted from the genotype. Our mutation analysis confirmed the importance of mutations in the SLC26A4 gene among hearing loss patients with enlarged vestibular aqueduct and revealed the mutation spectrum, essential information when performing genetic testing.

労災認定において詐聴, とくに誇大難聴が存在することは広く知られているところである。今回我々は2006年1月から2009年12月までの4年間に当科を受診し騒音性難聴の労災認定を希望した14症例を対象として, 従来施行してきた検査に加えて聴性定常反応検査 (ASSR) を行った。詐聴の診断はASSR閾値と純音聴力閾値を比較し, 純音聴力閾値がASSR閾値よりも高い場合を詐聴とした。結果は14症例中7例 (50%) を詐聴と診断し, その7例いずれも難聴の存在自体は明らかであり誇大難聴と考えられた。詐聴と診断した7例中6例は, 従来行ってきた検査からも詐聴と診断可能であり, ASSR検査結果と一致した。これまで騒音性難聴の意見書作成の際に, 詐聴の判断に苦慮するケースを少なからず経験してきたが, ASSR検査を行うことによりこれまでよりも正確に詐聴の診断ができる可能性が考えられた。

今回我々は, 多人数の町民を対象とした岩木健康増進プロジェクトの一環として, 20歳以上の弘前市の旧岩木町民のうち956名に対して, 聴覚検診とアンケート調査を行い, 年代別聴力像と種々の検査項目との関連について検討した。年代別平均聴力閾値は年代順に上昇しており, 特に高音域でその上昇幅が増大していた。また, 男女別聴力像では, 1,000Hzにおいては男女間に有意差を認めなかったが, 4,000Hzにおいては50歳代以降の男性が女性に比べて有意に閾値が上昇していた。男性の騒音暴露の機会が多いことが誘因と考えられ, 農業従事者が多いという調査地域の特性がその一因ではないかと考えた。さらに, 耳鳴, 耳閉感, 難聴については, それぞれ32.2%, 15.9%, 36.9%の人が自覚していた。難聴を自覚する人は70歳代以降で多くみられたが, 耳鳴を訴える人は80歳代で減少した。

新生児聴覚スクリーニング (以下スクリーニング) は全国的に実施率が増加傾向にある。今回我々は青森県内産科施設に対し, アンケート調査を行い, スクリーニング状況を調査した。結果, 産科施設の6割が検査機器を保有しており, 県内でも地域差が認められた。さらにH16年, 17年の県内スクリーニング施行症例数の概算と, 同年の県の出生数から求めるスクリーニング実施率は約25%であり, 全国の報告からしても低いという結果であった。機器を持たない施設では経済的, 人手不足の問題から, 今後も導入予定がないという回答であり, 青森県での実施率向上には, 機器保有施設での全例施行, または機器のない施設での出生児を機器保有施設で検査するなどの対策を検討するべきではないかと思われた。今後は検査実施率の向上に向け, 産婦人科, 小児科と更なる協力体制をと考えている。

Patients with vertigo caused by psychological problems have increased in recent years. It has been reported that many outpatients with vertigo also suffer from depression. Selective serotonin reuptake inhibitors are widely used for the treatment of depression because of their efficacy and relatively favorable side-effects profile compared to those of tricyclic antidepressants. We used Paroxetine to treat patients with vertigo who were diagnosed with depression by self-rating questionnaires for depression (SRQ-D). Twenty-six patients experienced relief after taking Paroxetine. Fifteen of them were relieved of their vertigo symptoms, 8 were improved, one was not changed, and two were worse. SRQ-D scores were compared between the day of commencement and the day after 4 weeks. Fifteen patients were normalized. Side effects occurred in seven patients; nausea in five and sleepiness in two. The average duration of taking the medicine was 24.4 weeks. Since Paroxetine showed beneficial clinical effects for patients with vertigo, this medicine might be useful for vertiginous patients with depression.

A 12-year-old male experienced left-sided hearing impairment, tinnitus, and vertigo after being hit by a volleyball. Pure tone audiometry showed severe, mixed left hearing loss and nystagmus to the right side. We diagnosed perilymphatic fistula and treated it conservatively. After ten days, his vertigo had disappeared and hearing on his left side showed improvement except at 2,000 and 8,000 Hz. However, he experienced slight dizziness after discharge from our hospital. About eleven months later, because of severe vertigo, he again came to our hospital. We diagnosed benign paroxysmal positional vertigo (BPPV) based on his symptoms and the characteristic nystagmus. We performed the Epley maneuver, and his vertigo and nystagmus disappeared the next day. Exploratory tympanotomy was carried out, but no sign of a perilymphatic fistula was detected. He experienced BPPV again, and so we tried the Epley and Lempert maneuver. We believed his prolonged dizziness was due to a partial collapse of the utricular wall, a condition called floating labyrinth. This phenomenon may occur with migration of otoliths from the utricle, leading to BPPV.

The development of motor protein activity in the lateral membrane of the mouse outer hair cell (OHC) from postnatal day 5 (P5) to P18 was investigated under whole-cell voltage clamp. Voltage-dependent, nonlinear capacitance (C (v)), which represents the conformational fluctuations of the motor molecule, progressively increased during development. At P12, the onset of hearing in the mouse, C (v) was about 70% of the mature level. C (v) saturated at P18 when hearing shows full maturation. On the other hand, C (lin), which represents the membrane area of the OHC, showed a relatively small increase with development, reaching steady state at P10. This early maturation of linear capacitance is further supported by morphological estimates of surface area during development. These results, in light of recent prestin knockout experiments and our results with quantitative polymerase chain reaction, suggest that, rather than the incorporation of new motors into the lateral membrane after P10, molecular motors mature to augment nonlinear capacitance. Thus, current estimates of motor protein density based on charge movement may be exaggerated. A corresponding indicator of motor maturation, the motor's operating voltage midpoint, V (pkcm), tended to shift to depolarized potentials during postnatal development, although it was unstable prior to P10. However, after P14, V (pkcm) reached a steady-state level near -67 mV, suggesting that intrinsic membrane tension or intracellular chloride, each of which can modulate V (pkcm), may mature at P14. These developmental data significantly alter our understanding of the cellular mechanisms that control cochlear amplification and provide a foundation for future analysis of genetic modifications of mouse auditory development.

When we treat patients with pollen allergy, we require correct information about pollen release. The total count of pollen and the date of first pollen release are strongly influenced by local weather conditions, so we wanted to predict local pollen release. Patients have degrees of sensitivity to pollen, with symptoms triggered in some cases by only small amounts. Therefore, we wanted to determine the previous dates of first pollen release (A), the first of two consecutive dates when one (count/cm2) or more grains were released (B), and the first of two consecutive dates when ten (count/cm2) or more grains were released (C). Aomori Prefecture has three different weather zones because it is surrounded by three oceans the Sea of Japan, the Pacific Ocean, and Mutsu Bay. We predicted pollen release in the major cities--Aomori, Hirosaki, and Hachinohe. Using nine years (1996-2004) of temperature data for each city from January 1 through February 1, we recorded the number of days in which the daily highest temperature was higher than each of five set temperatures (0 degree C, 1 degree C, 2 degrees C, 3 degrees C, 4 degrees C) up to the dates of A, B, and C. Multiple recordings were made for each year with the initial date of recording staggered at 10-day intervals. We then calculated the standard deviation and the efficient of variation of total days and totals of temperatures over set temperatures. For Aomori, results indicated that A was predicted as day 19 with temperatures over 4 degrees C after January 21. B was day 23 over 4 degrees C after January 21. C was the day 31 with over 4 degrees C after January 21. For Hirosaki, A was expected to be day 26 having temperatures over 0 degrees C after February 1. B was day 21 over 3 degrees C after February 1. C was day 30 over 3 degrees C after January 21. For Hachinohe, A was day 34 with temperatures over 0 degrees C after February 1. B was day 33 over 1 degree C after January 21. C was day 27 over 4 degrees C after January 21. We examined the day of pollen release in 2005.

In conductive hearing loss with an intact ear drum, even though preoperative examinations including audiometry, tympanometry and CT scan are applied, exploratory tympanotomy is necessary to make an exact diagnosis of ossicular interruption and stapes fixation. In the exploratory tympanotomy, if an ossicular problem is detected during the procedure, it is usually followed by ossicular reconstruction surgery.Our current strategy for treatment of conductive hearing loss without tympanic membrane perforation is presented.The presurgical diagnosis is made in the outpatient clinic by transtympanic endoscopy through the circular and non-hemorrhagic perforation made by laser-assisted myringotomy (LAM). An endoscopic view of the ossicular chain through 30- or 70-degree angled tip endoscopes held immediately to the outer side of the perforation was obtained to diagnose conduction disturbance locus in conductive hearing loss cases. Precise preoperative diagnosis is useful for patient counseling, surgical indications and planning.When an ossicular interruption is diagnosed, endoscopic transtympanic tympanoplasty (ETT), a newly developed minimally invasive procedure, is planned. In the endoscopic visualization through the dry, circular myringotomy perforation using a 1.9mm diameter rigid angled endoscope, ossiculoplasty was performed by inserting a trimmed tragal cartilage through the myringotomy perforation. As opposed to conventional methods, this procedure does not require surgical exposure such as otosclerosis drilling and skin incision, and avoids the substantial risk of unnecessary injury to the chorda tympani. ETT for a disrupted ossicular chain is an adequate and minimally invasive procedure and should prove a useful surgical procedure in future endoscopic tympanoplasty.

Japanese cedar is the most common pollinosis allergen in Japan. Predictions of total pollen counts and the first 2 or more days of the Japanese cedar pollen season are beneficial to patients. We developed predictive methods for those 2 factors in Hirosaki. We conducted an atmospheric Japanese cedar pollen survey from 1996 to 2002 in Hirosaki and compared yearly data with the male flowering index counted in 50 cedar trees in the preceding autumn. The male flowering index correlated highly positively with total cedar pollen counts in regression analysis, indicating its usefulness in predicting total pollen counts. Although the number of days from January 1 to the first day of continuous pollen emission showed no correlation with the cumulative maximum temperature during these days, the number of days from the day of first detection of pollen emission (minimum of 1 particle per sq. cm) to the first day of continuous pollen emission correlated highly with the cumulative maximum temperature and cumulative amount of snowfall on these days, suggesting that it is possible to predict the first day of continuous pollen emission by the cumulated daily maximum temperature after the day of first detection of pollen emission.

It has been reported that the sensitization to house dust-mites (HD-mites) is one factor which affects the onset of Japanese cedar (JC) pollinosis. So, we investigated whether sensitization to HD-mites affected the incidence and age of onset of JC pollinosis in 126 outpatients and 351 medical students.Allergic subjects who visited allergy clinics in Hirosaki University Hospital were classified into two groups based on the CAP results for JC and HD-mites; one was JC-positive and HD-mite-negative, and the other was JC-positive and HD-mite-positive. The former showed a higher age at onset of JC pollinosis than the latter. With regard to the CAP score for JC, there were no significant differences. This result seems to suggest that sensitization to HD-mites affects the onset of JC pollinosis.The medical students were also divided in the same manner. The incidence of JC pollinosis in the JC-positive and HD-mite-negative group was significantly higher than that in the JC-positive and HD-mite-positive group. Regarding orchard grass (OG) pollinosis, the incidence in the HD-mite-negative group was significantly higher than that in the HD-mite-positive group. Since pollinosis is related to the degree of exposure to the dominant pollen antigen, the students were divided by their native area (Kanto area, JC dominant; Tohoku/Hokkaido area, OG dominant). The incidence of JC pollinosis was highest in JC-positive and HD-mite-negative students from the Kanto area, and that of OG pollinosis was highest in OG-positive and HD-mite-negative students from the Tohoku/Hokkaido area. These results suggested that exposure to the dominant pollen antigen is most important to onset of pollinosis, although sensitization to HD-mites affects the onset of JC pollinosis.

We report a case of unilateral idiopathic stenosis of the internal auditory canal, without middle or inner ear anomalies. The patient, a 17-year-old female, presented with right deafness. High resolution computed tomography of the temporal bone showed stenosis of the right internal auditory canal. ABR stimulated from the right ear showed no response and bilateral DPOAE levels were within normal limits. These results implied that the outer hair cell function was well preserved, although damage to the inner hair cells and/or cochlea nerve was severe. It seems that evaluation by both ABR and OAE is necessary to determine the cause of hearing loss due to idiopathic stenosis of the internal auditory canal.

We report a case of otogenic intracranial complication. The patient was a 34-year-old female who complained of left otalgia and headache. She was hospitalized because of deterioration of her level of consciousness and high fever. On examination, her cerebrospinal fluid showed an elevated cell count. A bacterial culture of the otorrhea and cerebrospinal fluid found Streptococcus pneumoniae. A CT scan showed left acute otitis media and mastoiditis with paranasal sinusitis of the same side. This patient was successfully treated with intravenous antibiotic therapy without surgery. After she recovered, a CT scan with coronal sections showed bony defects and a thin bony wall in the left tympanic and mastoidal tegmina. This suggested that in this case the bacterial meningitis was secondary to acute otitis media and mastoiditis.When headache and high fever persist in patients with otitis media, we should suspect intracranial complications.

Mutation analysis of the PDS gene and the EYA1 gene, which are reported to be responsible for hearing loss associated with ear anomalies, was performed in 24 deaf patients with various middle and inner ear anomalies. The present study was done to clarify the spectrum of middle and inner ear malformations covered by these two genes. PDS mutations were found only in patients with enlarged vestibular aqueducts and EYA1 mutations were detected only in patients with ear pits and cervical fistulae, indicating that these two genes are associated with particular forms of middle and inner ear malformation. The genetic approach provides a strong tool for the diagnosis of hearing loss associated with ear anomalies.

We treated a patient suffering from a huge lipoma of the neck, which extended into the parapharyngeal space. CT scans and MRI were useful for the diagnosis and we extirpated the lipoma by incising the parotid gland. CT scans, MRI and operative findings showed that this was a case of a very rare lipoma originating in the deep lobe of the parotid gland.

Advances in molecular genetics have recently revealed that mutations in the EYA1 gene are responsible for branchio-oto-renal (BOR) syndrome in European and other populations. This is the first report confirming that an EYA1 gene mutation is also disease-causing in an Asian population. We have described one Japanese BOR syndrome family showing a novel mutation in exon 7 of the EYA1 gene. There was extensive variation of clinical phenotypes within this family. When the physician is confronted with a BOR family showing a wide variation in clinical expression, molecular genetic testing helps to achieve accurate diagnosis.

Mitochondrial mutations are known to be one of the causes of non-syndromic sensorineural hearing loss (SNHL). Of these mutations, a 1555A→G mutation has been reported to cause susceptibility to aminoglycoside antibiotics. The pedigrees shown in this study revealed maternal inheritance exclusively of the hearing impairment, consistent with the hypothesis of a mitochondrial inheritance. Although the hearing loss found in these patients sharing the 1555 mutation exhibited individual variation, there were some common features. Many subjects who harbor this mitochondrial mutation exhibited mild, high frequency, progressive hearing loss even without aminoglycoside injections. Regardless of aminoglycoside exposure, the hearing loss was usually associated with permanent tinnitus. Most of our patients had no history of vestibular dysfunction, such as dizziness and/or vertigo. The results presented here support the hypothesis that the A1555G mutation may play a more general role in causing hearing loss. This indicates the necessity for widespread screening of this mutation in the general population.

The expression of glutathione S-transferase (GST)-pi and four oncogene products, c-Jun, c-Fos, c-H-Ras, and c-Myc, in human squamous cell carcinomas of the head and neck was investigated immunohistochemically before and after radiation therapy, to examine whether these oncogene products might be involved in GST-pi expression, and also to examine the relationship between their expression and therapeutic response. Clinical response to radiation was evaluated in terms of both tumor regression and relapse over two-year follow-up periods. The overall positive rates in 83 carcinoma specimens before therapy were 60.2% for GST-pi and 28.9-51.8% for the individual oncogene products, the positive rates for the oncogene products being higher in GST-pi-positive than in GST-pi-negative cancers. c-Jun was most highly correlated with GST-pi expression. Following radiation, the expression of GST-pi and the oncogene products was altered in about a half of 30 patients. Eleven of the 18 patients who exhibited prior positivity for GST-pi showed negative conversion, while 4 of the 12 patients with prior negativity demonstrated positive conversion. In most cases, changes in c-Jun staining coincided with those in GST-pi. Regarding clinical response to radiation therapy, the positive rates for GST-pi and c-Jun before radiation were higher in the residual cancer or relapse cases than in the group showing complete response without relapse. Examination of 26 patients with laryngeal cancer revealed that relapse occurred more frequently in cases exhibiting positive reactions for GST-pi, c-Jun, or c-H-Ras. These results suggest a direct link between c-Jun and GST-pi in head and neck cancers before and after radiation. Although GST-pi and the oncogene products can be influenced by radiation, GST-pi and c-H-Ras expression may be a risk factor for relapse of laryngeal cancer.

The present study investigated the immunocytochemical localization of putative neurotransmitters/neuromodulators and their receptors in the vestibular periphery.Excitatory amino acids, such as glutamate and aspartate are abundant in hair cells, indicating that these amino acids may be candidates for hair cell transmitters. The level of glutamate is significantly higher in both types of hair cells, in contrast with the glutamine level which is significantly higher in supporting cells only. This complementary localization pattern is consistent with the existence of a glutamate-glutamine cycle between hair cells and supporting cells. The existence of NMDAR1 and AMPA type, GluR2/3, 4 glutamate receptors in the vestibular ganglion cells further supports the hypothesis that glutamate may serve as a hair cell transmitter.Primary afferent neurons (vestibular ganglion cells) can be divided into at least two chemically distinct subpopulations based on the consentrations of a neuropeptide (substance P). Substance P-immunoreactive small ganglion cells may receive information from the peripheral region of the endorgans.In addition to acetylcholine, a known efferent neurotransmitter, CGRP and GABA are also distributed in vestibular efferent neurons. The localization of CGRP- and GABA-like immunoreactivities found in the efferent nerve fibers varied according to species. This difference in the distribution patterns of neuroactive substances, found in the efferent system, may indicate that each species has a chemically (and probably functionally) distinct efferent system related to the specific environment and/or evolution.

The prevalence and factors relating to the appearance of nasal allergies were investigated, in a group of 351 medical students. The prevalence of nasal allergies in the 351 students was 39.6%. About 56% of the students were sensitized by some inhalation antigen. The primary antigens among the students who had grown up in Aomori Prefecture were house dust, mites and orchard grass.It was suggested that the appearance of nasal allergies is nearly always due to the presence of both environmental and hereditary factors.

To investigate the pathophysiology of benign paroxysmal positional vertigo (BPPV), we observed positional nystagmus and assessed the efficacy of the canalith repositioning procedure (CRP). Nystagmus was recorded using an infrared CCD camera. Subjects were 36 patients who exhibited typical rotatory nystagmus of BPPV with Hallpike maneuvers. The therapy given to the control group (Group A, n=18) was medication only, while Group B (n=18) was treated by both CRP and medication. In almost all patients, rotatory nystagmus was provoked by slow position change from the healthy ear down (head hanging position with a 45-degree tilt to the healthy side) to the affected ear down (head hanging position with a 45-degree tilt to the affected side). This phenomenon indicates that rapid movement is not necessary for provocation, and a 45-degree off sagittal tilt indicates that the lesion is in the posterior semicircular canal. The period of disease in Group B was significantly shorter than that in Group A. In Group B, CRP was effective in 16 patients (89%). We conclude that free-moving particles in the posterior semicircular canal is the cause of BPPV. We suggest that rotatory positional nystagmus is a result of ampullofugal flow of sinking particles in the posterior semicircular canal and secondary ampullof ugal flow in the anterior semicircular canal.

To determine age-related changes in vestibular compensation we measured the frequency of spontaneous nystagmus and yaw head tilt after unilateral labyrinthectomy. Albino guinea pigs were divided into two groups: the control group (3 to 12 months of age; n=8) and the aged group (36 to 39 months of age; n=3). We found that the frequency of spontaneous nystagmus in the aged group was significantly lower than in the control group (p

Cholesterol is an essential component of cell membranes, and determines their rigidity and fluidity. Alterations in membrane cholesterol by MβCD or water-soluble cholesterol affect the stiffness, capacitance, motility, and cell length of outer hair cells (OHCs). This suggests that reconstruction of the cytoskeleton may be induced by cholesterol alterations. In this study, we investigated intracellular signaling pathways involving G proteins to determine whether they modulate the changes in voltage-dependent capacitance caused by cholesterol alterations. Membrane capacitance of isolated guinea pig OHCs were assessed using a two-sine voltage stimulus protocol superimposed onto a voltage ramp (200 ms duration) from −150 to +140 mV. One group of OHCs was treated with 100 μM guanosine 5′-O-(3-thiotriphosphate) tetralithium salt (GTPγS), the GTP analog, administrated into individual cells via patch pipettes. Another group of OHCs was internally perfused with 600 μM guanosine 5′-(β-thio) diphosphate trilithium salt (GDPβS), the GDP analog. A third group was perfused with internal solution only as a control. Application of 1 mM MβCD shifted non-linear capacitance curves to the depolarized direction of the control group with reduction of the peak capacitance (C mpeak). After the 10-min application of MβCD, shifts of voltage at C mpeak (V cmpeak) and reduction of C mpeak were 73.32 ± 11.09 mV and 9.09 ± 2.10 pF, respectively (n = 4). On the other hand, in the GTPγS-treated group, the shift of V cmpeak and reduction of C mpeak were attenuated remarkably. The shift of V cmpeak and reduction of C mpeak in the 10-min application of MβCD were 9.73 ± 10.92 mV and 3.08 ± 1.91 pF, respectively (n = 7). MβCD decreased the cell length by 16.53 ± 4.27 % in the control group and by 6.45 ± 6.22 % in the GTPγS group. In addition, we investigated the effects of GDPβS on cholesterol-treated OHCs. One millimolar cholesterol was externally applied after the 4-min application of 1 mM MβCD because the shift of V-C m function caused by cholesterol alone was small. Application of cholesterol shifted V-C m curves of the control group to the hyperpolarized direction with increase of the C mpeak. After the 10-min application of cholesterol, changes of V cmpeak and C mpeak were −9.19 ± 6.68 mV and 2.14 ± 0.44 pF, respectively (n = 4). On the other hand, in the GDPβS-treated OHCs, the shift of V cmpeak and increase of C mpeak were attenuated markedly. The shift of V cmpeak and increase of C mpeak after 10 min were 5.13 ± 10.46 mV and −0.55 ± 1.39 pF, respectively (n = 6). This study demonstrated that internally perfused GTPγS inhibited the MβCD effects and GDPβS inhibited the cholesterol effects, raising the possibility that G proteins may be involved in outer hair cell homeostasis as well as the possibility that cholesterol response may be G protein mediated. More study is required to clarify the detailed role of G proteins in the relation between cholesterol and the OHC cytoskeleton.

Three patients with traumatic positional vertigo were neurotologically examined. The first and second patients were middle-aged females who had suffered head injuries in traffic accidents. The first patient had left total deafness, and the second patient had no cochlear symptoms. The third patient was a male worker who was injured by falling rocks and had right sensorineural hearing loss. In all the three patients, we found brisk rotatory nystagmus accompanied with vertigo in the head hanging position. The theory of free-floating particles in the posterior semicircular canal seems to explain the rotatory nystagmus and the gradual decrease in its intensity. On the basis of this theory, a canalith repositioning procedure (CRP) was performed in all three patients. It was effective in the second and third patients, but in the first patient positional nystagmus and vertigo were unchanged.

The sympathetic nervous system, which originates in the superior cervical ganglion (SCG) and is distributed in vestibular end organs, has been proposed to have some influence on vestibular function. The present investigation was conducted to assess the effects of unilateral electrical stimulation of the SCG, administration of a vasopressor drug, and introduction of KCl (0.7 M/ml) into the tympanic cavity on vestibular function in alert guinea pigs. Nystagmus was not observed as result of electrical irritation of the SCG (22 test animals), infusion of the KCl solution into the middle ear cavity (5 test animals), or the combination of SCG stimulation and vasopressor drug administration (7 test animals). However, when the SCG was stimulated electrically after introduction of the KCl solution into the ipsilateral cavity, nystagmus and postural deviation were observed (5 out of 12 animals). Furthermore, after the administration of a vasopressor drug to these 12 animals, irrespective of the manifestation of nystagmus, the same changes took place in response to the electrical stimulation (7 animals). These results suggest that SCB stimulation is a provocative factor for nystagmus, that infusion of KCl solution into the tympanic cavity induces a hypersensitive state in the inner ear, and that high blood pressure increases this hypersensitivity.

Using infrared CCD camera and electronystagmography, we analyzed positional nystagmus in 33 patients with peripheral positional vertigo.1) Patients were classified into three categories: (a) lateral type: horizontal nystagmus occurs in lateral position; (b) sagittal type: rotatory nystagmus occurs in head-hanging position (so-called benign paroxysmal positional vertigo); and (c) mixed type.2) Vertigo and nystagmus began with a few seconds latency after the head was tilted, briefly increased to a maximum, and then gradually decreased.3) In all types, the number of female patients was greater than that of male patients.4) In the lateral type, the mean period from the onset to the disappearance of vertigo was about 3 weeks. However, in those with the sagittal type or mixed type it was much longer.5) The intensity of positional nystagmus was influenced by the direction of gravity in all types.The free-floating particles theory seems to be able to explain the latency of the nystagmus, the gradual decrease in its intensity, and recurrence of the vertigo. Lateral type lesions are thought to be in the lateral semicircular canal, and sagittal type lesions perhaps in the posterior semicircular canal; mixed type lesios are thought to be in both.

Triludan® was administered to 75 patients with Japanese cedar pollinosis to determine its effectiveness and safety. Triludan® was effective not only in patients who started using it before the beginning of the pollen season, but also in those who began taking it after the season had started. The drug was most effective for “sneezing” and “rhinorrhea”, but “nasal obstruction” was not so markedly improved. Side effects were reported by six patients (7.9%), three of whom complained of drowsiness.

A 9-year-old boy with the Kabuki make-up syndrome visited our clinic. His face had the appearance of a Kubuki actor, and he had cleft palate. Bilateral mixed hearingloss was noted by audiometry, and a caloric test showed bilateral canal paresis. Temporal bone CT showed Mondini dysplasia in both inner ears.

A careful analysis was made of the results of electronystagmography in 3 patients with spontaneous vertical nystagmus, and the causes of their nystagmus are discussed.Case 1 : a 24-year-old man showed primary position upbeat nystagmus with large amplitude (4°-6°) and 2 Hz frequency, which decreased on upward gaze and increased on downward gaze. This nystagmus changed to downbeat nystagmus when convergent gaze was maintained. Marked bilateral diminution of vestibular response was noted during rotation tests and caloric tests.Case 2 : an 80-year-old man had primary position downbeat nystagmus at a frequency of 1.5Hz and an amplitude of 2°-4°, which was not influenced by changes of eye position. Vertical optokinetic nystagmus tests were abnormal, but other neuro-otological findings were almost normal.Case 3 : a 47-year-old woman showed primary position downbeat nystagmus with small amplitude (1°-2°) and 3 Hz frequency, which increased in intensity in the supine right-side-down position and changed to an upward vector in the head-hanging-position. VOR gain was greater than normal. There was almost total absence of visual suppression of caloric nystagmus.The nystagmus observed in Case 1 seemed to reflect bilateral dysfunction of the caudal brainstem, including both vestibular nuclei, resulting from Wernicke's encephalopathy. The nystagmus in Case 3 originated from caudal brainstem compression by a large menigioma. In Case 2, no diagnosis was established.

The immunocytochemical localization of substance P (SP) in vestibular endorgans of various mammals (rat, guinea pig, rabbit, squirrel monkey, and man) was investigated. SP-like immunoreactivity was found in all the vestibular endorgans studied. Most SP immunoreactive fibers were thick and distributed around or beneath sensory hair cells. A smaller group of SP immunoreactive varicose thin fibers was present in the stroma of vestibular endorgans, nerve trunks, and along blood vessels around the vestibular nerves. The former, probably corresponding to the afferent nerve endings of hair cells, was found predominantly in the peripheral region of each endorgan. There were no great species differences in staining patterns, except in rat vestibular endorgans, where numerous thin SP immunoreactive fibers were distributed beneath the sensory epithelium. SP immunoreactive fibers were also found in human vestibular endorgans, suggesting that SP may play an important role in human vestibular function.

The value of the radio allergosorbent test (RAST) in the detection of specific IgE antibody has been investigated by many researches.However, the clinical usefullness of the CAP-fluoro enzyme immuno assay (CAP-FEIA) method recently introduced for the same purpose as the RAST method is still not clear. The authors used both the RAST and the CAP-FEIA methods to test the same patients with nasal allergy and compared the results.It was found that the CAP-FEIA method was more sensitive than the RAST method in the detection of specific IgE antibodies to single or multiple antigens in patients with nasal allergy, except for house dust antigens. Further investigation showed that the lower sensitivity to house dust antigen was due to the impurities in the house dust extract.Reexamination with a new standard house dust extract showed as high sensitivity as to the other antigens. The CAP-FEIA method showed a better correlation with the results of skin tests than did the RAST method.It is concluded that CAP-FEIA is an excellent method for the diagnosis of nasal allergy.

The detectability of bone destruction is discussed and a comparison is presented of Caldwell's and Waters' views, maxillary tomography and CT scans of 10 patients with maxillary cancer. Destruction of the lateral wall of the maxillary sinus was confirmed in all 10 patients by CT scan, but destruction of the tuber maxillary line (T-M line) could not be seen in Caldwell's and Waters' views in 5 of the patients. As a rule, frontal tomography was helpful in the observation of the orbital base, the median wall of the maxillary sinus and the nasal cavity. However, CT scan was the best method, and accurate with observation of the anterior wall of the maxillary sinus was possible only with axial CT.

The gene responsible for DNFB1 and DFNA3, connexin 26 (GJB2), was recently identified and more than 20 disease causing mutations have been reported so far. This paper presents mutation analysis for GJB2 in Japanese non-syndromic hearing loss patients compatible with recessive inheritance. It was confirmed that GJB2 mutations are an important cause of hearing loss in this population, with three mutations, 235delC, Y136X, and R143W, especially frequent. Of these three mutations, 235delC was most prevalent at 73%. Surprisingly, the 35delG mutation, which is the most common GJB2 mutation in white subjects, was not found in the present study. Our data indicated that specific combinations of GJB2 mutation exist in different populations. Keywords: connexin 26; GJB2; Japanese; non-syndromic hearing loss

Three cases of maxillofacial trauma could be more precisely diagnosed by three dimensional computed tomography, which showed stereotaxically the extent and course of the fracture-line. The stereotaxic investigation of pre- and post- operative X-ray images, not only improves the effectiveness of surgery, but also makes possible a more exact evalution of what reconstructive procedure can be performed.

A statistical analysis was made on 639 cases of esophageal foreign bodies treated in the Department of Otorhinolaryngology, Hirosaki and Tohoku Universities, during the years from 1949 to 1989 and from 1972 to 1989, respectively. The results were as follows:1) The annual mean incidences of the disease were 9.8 and 13.3 at Hirosaki and Tohoku Univ., respectively. Year-to-year change in the incidence was not observed.2) Male and female ratio was 4: 3, and 327 cases (51%) were under 6 years of age.3) The foreign objects were coins (44%), fish bones (19%), dentures (12%), P.T.P. (press through pack of medicine, 4%) and others.4) Comparison of the foreign objects between two periods, 1949-61 and 1982-89, revealed that the frequencies of the disease due to coins and fish bones decreased. P.T.P. and meat as foreign bodies occurred in the later period. These tendencies led to an increased variety of objects in recent years.5) In the urban area the trends noted in 4) were more prominent than in the rural area.6) It was noteworthy that in the rural area the aspiration of dentures was more frequent thanin the urban area.7) Approximately 70% of the foreign bodies were lodged at the entrance of esophagus.8) Complications of the disease, such as periesophageal abscess, mediastinitis and aspiration pneumonia, occurred only in 7 out of 303 cases in the recent 18 years.

Five patients with typical manifestations of vestibular neuronitis were examined repeatedly for spontaneous nystagmus, positional nystagmus, caloric responses and Contraves rotation test results determined by electronystagmography.1) Spontaneous nystagmus was observed for more than 2 months. The duration of spontaneous nystagmus in patients with vestibular neuronitis was longer than patients in those with other acute vestibular disorders.2) No patient showed direction-changing positional nystagmus, but in 2 cases, nystagmus amplitude was increased in the supine healthy-ear-downn position.3) Four of 5 patients showed no caloric reaction on the affected side in the early stage of the disease; however, at the follow-up examination after several months, all patients showed reappearance of the caloric responses.4) In the rotation test, all patients showed directional preponderance to the healthy side, but the “recruitment type”, which is observed exclusively in disturbances of the vestibular organ, was not observed in any patient.5) It was thought that vestibular neuronitis represented a neuropathy due to a viral infection, such as varicella zoster or herpes simplex.

The 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors, also called statins, are commonly used as lipid-lowering drugs that inhibit cholesterol biosynthesis. An anticancer effect, as a pleiotropic function of certain statins, has been hypothesized. In the present study, we investigated the effect of simvastatin, one of the natural statins, on cell proliferation, cell cycle, invasive activity, and molecular expressions associated with cell-extracellular matrix adhesion, signal transduction, and DNA synthesis in Tu167 and JMAR cells from head and neck squamous cell carcinoma. The addition of simvastatin resulted in a dose-dependent inhibition of cell growth and migration into the extracellular matrix. Considerable morphological changes occurred after treatment with simvastatin, demonstrating loss of cell adhesion and disruption of actin filaments in cytoplasm. The inhibitory effect of simvastatin on cell proliferation seemed to be associated with cell cycle arrest and increased expression of p21, p27, and activated caspase-3. The expression of beta1-integrin, a counter adhesion for the extracellular matrix, phosphorylated FAK, and phosphorylated ERK was decreased by treatment with simvastatin. The proapoptotic effect of simvastatin was inhibited by treatment with mevalonate. cDNA microarray assay demonstrated that molecular changes resulting from treatment with simvastatin included the up-regulation of cell cycle regulators and apoptosis-inducing factors and the down-regulation of integrin-associated molecules and cell proliferation markers. Of down-regulated genes induced by simvastatin treatment, a significant depletion of thymidylate synthase was confirmed using western blot analysis. These results imply that simvastatin has the potential to be effective for the prevention of the growth and metastasis of cancer cells.

Inner ear hair cells play a major role in the auditory pathway that converts sound stimulation into electrical signals, and then into a neural code. However this function is often lost by aminoglycoside ototoxicity. The injury of inner ear hair cells from aminoglycoside treatment is considered apoptosis, and caspase is an important participant in the apoptosis pathway in many organs. It has been reported that calpain, a calcium-dependent protease, is essential for mediation and promotion of cell death. The purpose of the present study was to investigate effects of caspase and calpain inhibitors on the inner ear hair cells after aminoglycoside treatment, and to explore the cell death pathway. Cochlea explant cultures were prepared from mice of postnatal 6 days, cultured with neomycin and/or protease inhibitors, and then stained with phalloidin-fluorescein isothiocyanate (phalloidin-FITC), which was used as a marker to identify surviving hair cells. We demonstrated that neomycin (0.1-1 mM) reduced the number of outer hair cells in a dose-dependent manner. Furthermore, we showed that leupeptin, a calpain inhibitor, significantly protects against the neomycin-induced loss of outer hair cells, whereas a caspase inhibitor was effective only against a lower concentration of neomycin (0.2 mM). Using the TdT-mediated dUTP-biotin nick and labeling method, we also found that a calpain inhibitor, but not a caspase inhibitor, prevents apoptotic DNA fragmentation after treatment with 1 mM neomycin. These results suggest that calpain, rather than caspase, may be responsible for apoptosis induced by aminoglycoside. Thus, leupeptin may prevent hearing loss from aminoglycoside ototoxity.

We surveyed the prevalence of obesity in the general population in Jamaica, and examined the relationship between it and lifestyle. The survey population consisted of 1,935 inhabitants in Jamaica, whose body weight, height, marital status, educational history, employment status and other obesity-associated lifestyle factors were surveyed. Six major findings emerged. The first finding is that the proportion of obesity in women was very high, and there was a big gender difference. Secondly, a lower prevalence towards obesity was associated with cohabitation of the subjects in both genders, and higher educational levels in female subjects. Thirdly, the proportion of the subjects who considered their weight to be quite acceptable was higher in the obese/overweight groups in both genders. Fourthly, exercise frequency showed a negative correlation with the body mass index (BMI) in men, and the frequency of exercising was apparently lower in women than in men. Fifthly, as for dietary factors, in both genders vegetables showed a negative correlation with the BMI. Sixthly, non-smokers were also associated with a lower obesity prevalence in men. In conclusions, these findings suggest that social and lifestyle factors such as the educational level, marital status and dietary habits of the general population influence Jamaican obesity.

Adenoid cystic carcinoma, a relatively uncommon tumor of salivary glands, is characterized by a prolonged clinical course and a fatal outcome. The molecular events underlying their progression are unknown. In this study, we examined the methylation status of E-cadherin gene and its protein expression in 23 cases of adenoid cystic carcinoma and correlated the results with the clinicopathologic factors to determine its role in these tumors. We also analyzed the effect of 5-azacytidine on the re-expression in a methylated cell line of adenoid cystic carcinoma for this gene. In our study, E-cadherin immunoreactivity, although heterogeneous, showed a progressive reduction with high histological grade and in metastatic and recurrent lesions. Promoter methylation was detected in 16 of 23 cases (70%), but there was no correlation with the histological grade or patient prognosis. Microdissection of immuno-negative cells in heterogeneous tumors showed positive methlyation. In the cell line from salivary adenoid cystic carcinoma with methylated E-cadherin, 5-azacytidine restored the E-cadherin expression. Our results indicate that: (1) E-cadherin gene promoter is frequently methylated in adenoid cystic carcinoma, leading to reduced E-cadherin expression, (2) variable E-cadherin expression might result from the intratumoral heterogeneity, and (3) increased extent of methylated areas may be associated with progression and advancement of the disease.

Enlarged vestibular aqueduct (EVA) is an inner ear anomaly occasionally associated with sensorineural hearing loss (SNHL) and/or dizziness. Recent genetic studies indicate that mutations in the PDS gene may cause EVA. A 10-year-old EVA patient who had undergone annual hearing tests for 7 years had an aunt and cousin who also had hearing loss and EVA, so genetic examinations were conducted for a possible genetic link. Two new PDS gene mutations, S610X and S657N, were found in all 3, including the proband. We discuss the importance of genetic analysis, which offers new insight into SNHL diagnosis and treatment in children.

Sixteen Japanese nonsyndromic autosomal dominant sensorineural hearing loss (ADSNHL) families were investigated clinically as well as genetically. Most families showed postlingual hearing loss. Although the severity of their hearing loss varied, most patients showed mild-moderate sensorineural hearing loss of a progressive nature. Mutation analysis was performed for the MYO7A, KCNQ4, and GJB3 genes, which are known to be responsible for autosomal dominant sensorineural hearing loss. The present study reports that a mutation in KCNQ4, a member of a large family of potassium channel genes, was responsible for ADSNHL in one Japanese family.