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The aims of this study were to evaluate the efficacy of partial parotidectomy using retrograde dissection of the marginal mandibular branch of the facial nerve for benign tumours of the parotid gland and to establish the indications for its use. We examined 106 consecutive patients with previously untreated benign tumours in the lower portion of the parotid gland who were treated by parotidectomy. The first group (anterograde group, n=52) consisted of those who had standard anterograde parotidectomy. The remaining patients, who underwent retrograde parotidectomy, were further divided into two groups: those in whom the upper edge of the tumour was located below the mastoid tip (below mastoid group, n=46) or those in whom it was above the mastoid tip (above mastoid group, n=8). The operating time was significantly shorter in the below mastoid group (141.2, 127.5, and 98.1minutes, respectively) as was intraoperative blood loss (41.1, 53.0, and 24.4ml, respectively), compared with the other two groups. There was a higher incidence of facial nerve dysfunction in the above mastoid group postoperatively (4/8) than in the other two groups. The results suggested that the presence of a tumour of any size located below the mastoid tip is a good indication for parotidectomy using retrograde dissection of the marginal mandibular branch of the facial nerve.

Salivary duct carcinoma is a highly aggressive disease with a poor prognosis. Surgical resection is currently the only curative treatment, as there is no effective systemic therapy for this malignancy. Recently, trastuzumab has been shown to exhibit therapeutic efficacy in the treatment of salivary duct carcinoma; similarly, molecularly targeted agents, such as cetuximab, are expected to be useful for salivary duct carcinoma treatment. We herein describe the case of a 56-year-old man diagnosed with salivary duct carcinoma in the left submandibular region, with ipsilateral multiple metastases to the neck lymph nodes. Radical resection of the tumor and submandibular gland with neck dissection were performed. One month after radical surgery, computed tomography (CT) scans indicated metastasis in the lower lobe of the left lung. CT-guided transthoracic fine-needle aspiration biopsy revealed a single metastasis and lung metastasectomy was immediately performed. The tumor cells of the primary lesion and those of the lung metastasis were immunohistochemically positive for epidermal growth factor receptor. One month later, multiple right lung metastases appeared, and the patient was treated with cisplatin/5-fluorouracil (5-FU) chemotherapy plus cetuximab, achieving a complete radiographic response. However, multiple lung metastases developed during adjuvant weekly cetuximab monotherapy. Subsequently, treatment with S-1 and weekly cetuximab was initiated, and the multiple lung metastases have been maintained as stable disease for 5 months. To the best of our knowledge, this is the first report of cetuximab use for the treatment of salivary duct carcinoma. Although cisplatin/5-FU chemotherapy plus cetuximab was efficacious in treating the lung metastasis, cetuximab monotherapy was insufficient for controlling tumor growth.

Presbycusis is the impairment of auditory function associated with aging, which stems from peripheral cochlear lesions and degeneration of the central auditory process. The effect of age-induced peripheral hearing loss on the central auditory process is not fully understood. C57Bl/6 (C57) mice present accelerated peripheral hearing loss, which is well developed by middle-age and mimics the human presbycusis pattern. The aim of this study was to elucidate the molecular effects of peripheral hearing loss in the inferior colliculus (IC) with age between young and middle-aged C57 mice using cDNA microarray. Glutamate receptor ionotropic NMDA ζ1 (GluN1) exhibited the greatest decrease in the middle-aged group as determined using cDNA microarray and by further assessment using real-time PCR (qPCR). Histological assessment with in situ hybridization of GluN1 showed significantly decreased expression in all IC subdivisions of the middle-aged group. GluN1 is a receptor for excitatory neurotransmission, and significant downregulation of this gene may be subsequent to the decline of afferent input from the cochlea in aging C57 mice. Consequently, using the combination of microarray, qPCR, and in situ hybridization, we showed that the decline of GluN1 in the IC of aging animals might have a key role in the pathogenesis of presbycusis.

Systemic air embolism, a very rare clinical condition, has many causes. We report a case of multiple air embolisms following laryngopharyngoesophagectomy salvage surgery for hypopharyngeal residual cancer after concurrent chemoradiotherapy. Cervical infection arose from a fistula caused by postoperative suture failure in which the 56-year-old man suddenly lost consciousness and went into shock. A few days post operation, an air embolism happened and caused in the brain, pulmonary, myocardiac and cerebral infarction. The man died two months after initial occurrence. We suspect that air entered through the ruptured left internal jugular vein via infection due to aspiration at the injury site. Air embolisms are associated with different medical maneuvers, and it is necessary to recognize that they may become a serious perioperative complication.

当科における遊離移植の現況を検討した。当科では，腸管移植を除いて，皮弁挙上から皮弁縫着，血管吻合まで全て頭頸部外科医がおこなっている。1987年に遊離組織移植を導入し，20年余りが経過したが，現在までに468症例（470皮弁）を経験した。使用した再建材料の内訳は，前腕皮弁147例，腹直筋皮弁128例，空腸173例，骨付き肩甲皮弁10例，腓骨皮弁6例，などであったが，近年は腹直筋皮弁と空腸が多用される傾向にあった。移植組織の生着率は94.0%であった。壊死症例の検討では，空腸使用例が多くみられ，原因として静脈血栓に起因するものが多かった。当科における根治的化学放射線療法の導入の時期に一致して，空腸壊死症例が増加していることから，術野における何らかの影響が示唆された。

Objectives We examined the effect of platelet-activating factor (PAF) on IL-8 production in cultured rat middle ear epithelial cells (RMECs), and the concentrations of cytokine, PAF, and PAF-acetylhydrolase (PAF-AH) were also examined in the PAF-induced experimental OME (otitis media with effusion) of rats. Methods Using an enzyme-linked immunospecific assay, we measured the levels of cytokines in the cultured RMECs and the PAF-induced OME of rats. The PAF was quantitated by the platelet-aggregating activity and the PAF-AH was measured by radioimmunoassay. Results Both PAF and C-PAF, which is a stable analogue of PAF, significantly induced production of IL-8 in the RMECs in a dose-dependent manner. The PAF-induced IL-8 production was abolished by co-incubation with WEB2170, a specific PAF receptor antagonist. The concentrations of the cytokines and PAF in the PAF-induced OME of rats were higher on day 1 and the PAF and cytokine levels seemed to correspond well with the persistence of OME. Conclusion PAF may stimulate the local production of cytokines and may induce OME in the middle ear.

This study demonstrates that the co-administration of lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF-alpha) (LPS/TNF-alpha) can induce the expression of inducible nitric oxide synthase (iNOS), which results in the generation of apoptosis in cultured human nasal microvascular endothelial cells (HNMECs). Since LPS and TNF-alpha have been suggested to play an important role in the pathophysiology of nasal disease, we conclude that microvascular leakage may therefore contribute to the inflammatory process in nasal disease, such as allergic rhinitis and asthma.The HNMECs were obtained from the inferior turbinate and subsequently cultured. The expression of iNOS induced by both the LPS and TNF-alpha was investigated by fluorescent immunohistochemistry, using confocal laser microscopy. The DNA-binding dye, Hoechist 33342, was also used to analyze the apoptosis in the HNMECs.The fluorescent immunohistochemistory study demonstrated that LPS and TNF-alpha induced the expression of iNOS in HNMECs. LPS/TNF-alpha remarkably augmented the expression of iNOS in HNMECs in comparison to stimulation by either LPS or TNF-alpha alone. LPS/TNF-alpha also induced apoptosis in HNMECs. 1400W, a highly selective inhibitor of iNOS, inhibited both the expression of iNOS and the apoptosis induced by LPS/TNF-alpha.

Background Several genes are candidates for treating inner ear diseases. For clinical applications, minimally invasive approaches to the inner ear are desirable along with minimal side-effects. Methods Adeno-associated virus (AAV) was used as a vector into the guinea pig inner ear. Six AAV-cytomegalovirus hybrids (AAV-2/1, -2/2, -2/5, -2/7, -2/8 and -2/9) were infused into perilymph of the cochlea basal turn, an approach that could be used in cochlear implant surgery. At 7 days after injection, distribution of gene expression, hearing and morphology were evaluated. Adenoviral vector was also used to compare distributions of gene expression. Moreover, distribution of cell surface receptors of AAV in the cochlea was examined using immunohistochemistry. Results Using the perilymphatic approach, adenovirus could be transferred to mesothelial cells lining the perilymph, but not sensory cells. Conversely, all AAV serotypes displayed tissue tropism to inner hair cells, with AAV-2/2 showing particularly efficient transfer to sensory cells. This tissue tropism of AAV could not be explained by the distribution of AAV receptors. Hearing and morphology were largely unaffected. Conclusions Our results indicate that AAV vector can be safely applied to the inner ear and AAV-2/2 offers a good tool for transferring transgenes into sensory cells of the inner ear efficiently without toxicity. Copyright © 2008 John Wiley & Sons, Ltd.

Nitric oxide (NO) production during hyposmotic stimulation in outer hair cells (OHCs) of the guinea pig cochlea was investigated using the NO sensitive dye DAF-2. Simultaneous measurement of the cell length and NO production showed rapid hyposmotic-induced cell swelling to precede NO production in OHCs. Hyposmotic stimulation failed to induce NO production in the Ca(2+)-free solution. L-N(G)-nitroarginine methyl ester (L-NAME), a non-specific NO synthase inhibitor and gadolinium, a stretch-activated channel blocker inhibited the hyposmotic stimulation-induced NO production whereas suramin, a P2 receptor antagonist did not. S-nitroso-N-acetylpenicillamine (SNAP), a NO donor inhibited the hyposmotic stimulation-induced increase in the intracellular Ca(2+) concentrations ([Ca(2+)](i)) while L-NAME enhanced it. 1H-[1,2,4]oxadiazole[4,3a]quinoxalin-1-one, an inhibitor of guanylate cyclase and KT5823, an inhibitor of cGMP-dependent protein kinase (PKG) mimicked effects of L-NAME on the Ca(2+) response. Transient receptor potential vanilloid 4 (TRPV4), an osmo- and mechanosensitive channel was expressed in the OHCs by means of immunohistochemistry. 4alpha-phorbol 12,13-didecanoate, a TRPV4 synthetic activator, induced NO production in OHCs. These results suggest that hyposmotic stimulation can induce NO production by the [Ca(2+)](i) increase, which is presumably mediated by the activation of TRPV4 in OHCs. NO conversely inhibits the Ca(2+) response via the NO-cGMP-PKG pathway by a feedback mechanism.

Information to the cerebellum enters via many afferent sources collectively known as precerebellar nuclei. We investigated the distribution of cholinergic terminal-like structures in the mouse precerebellar nuclei by immunohistochemistry for vesicular acetylcholine transporter (VAChT). VAChT is involved in acetylcholine transport into synaptic vesicles and is regarded as a reliable marker for cholinergic terminals and preterminal axons. In adult male mice, brains were perfusion-fixed. Polyclonal antibodies for VAChT, immunoglobulin G-peroxidase and diaminobenzidine were used for immunostaining. In the mouse brain, immunoreactivity was seen in almost all major cholinergic cell groups including brainstem motoneurons. In precerebellar nuclei, the signal could be detected as diffusely beaded terminal-like structures. It was seen heaviest in the pontine nuclei and moderate in the pontine reticulotegmental nucleus; however, it was seen less in the medial solitary nucleus, red nucleus, lateral reticular nucleus, inferior olivary nucleus, external cuneate nucleus and vestibular nuclear complex. In particular, VAChT-immunoreactive varicose fibers were so dense in the pontine nuclei that detailed distribution was studied using three-dimensional reconstruction of the pontine nuclei. VAChT-like immunoreactivity clustered predominantly in the medial and ventral regions suggesting a unique regional difference of the cholinergic input. Electron microscopic observation in the pontine nuclei disclosed ultrastructural features of VAChT-immunoreactive varicosities. The labeled bouton makes a symmetrical synapse with unlabeled dendrites and contains pleomorphic synaptic vesicles. To clarify the neurons of origin of VAChT-immunoreactive terminals, VAChT immunostaining combined with wheat germ agglutinin-conjugated horseradish peroxidase retrograde labeling was conducted by injecting a retrograde tracer into the right pontine nuclei. Double-labeled neurons were seen bilaterally in the laterodorsal tegmental nucleus and pedunculopontine tegmental nucleus. It is assumed that mesopontine cholinergic neurons negatively regulate neocortico-ponto-cerebellar projections at the level of pontine nuclei.

We report results of a retrospective study of 12 cases of adenoid cystic carcinoma (ACC) in the parotid gland. Local pain was often observed in ACC among other malignant parotid tumors. Although fine-needle aspiration cytology (FNA) was not effective for preoperative diagnosis, frozen section diagnosis (FS) during surgery showed excellent results. Cases with T3 or T4 underwent total or enlarged parotidectomy, but, often showed positive surgical margins. Postoperative radiation therapy seemed useful in these cases and the 5-and 10-year disease-specific survivals in these 12 cases were 90.0% and 80.8%. These compare favorably with other reports in the literature. All 12 cases showed NO and no cervical relapse with or without neck dissection, indicating little effectiveness in prophylactic neck dissection. Tumor size, positive surgical margins, and perineural invasion are risk factors for this tumor as mention previously. Patients with perineural invasion, especially preoperative facial nerve palsy (T4a), are more likely to fail than those with two other factors, so, it seems conceivable for cases of T4a to undergo more positive treatment with surgery and postoperative radiation.

Tumors arising in the parapharyngeal space are rare. We reviewed 13 cases of parapharyngral space tumors that had been operated on between 1999 and 2004, and investigated the preoperative diagnosis, method of operation, and complications after surgery. Computed tomography, magnetic resonance imaging and fine-needle aspiration cytology were very useful for preoperative diagnosis, judging the extent of involvement and localization, and assessing the pathology of the tumor in the parapharyngeal space. The pathological diagnosis of these tumors was pleomorphic adenoma (6 cases), neurilemmoma (5 cases), ganglioneuroma (1 case), and malignant pleomorphic adenoma (1 case). The cervical approach was the most common, and was used in seven cases. Other surgical approaches included the cervical approach with mandibulotomy (2 cases), cervical-parotid approach (2 cases), and parotid approach (2 cases). First bite syndrome (FBS) has recently been reported as a complication after surgical removal of parapharyngeal space tumors. We experienced 4 cases of FBS. Since FBS was very difficult to treat in these patients, it is necessary to be aware of this syndrome.

We report a 47-year-old woman with polyostotic fibrous dysplasia. She complained of a painless swelling of the left cheek since she was two years old. A craniofacial CT examination showed sclerotic changes of the left maxilla, sphenoid and temporal bone. Bone scintigraphy showed high uptakes at not only these craniofacial bones but also thoracic vertebrae, rib, left humerus and pelvis. A biopsy of the left maxilla bone was performed, and a histopathological examination showed fibrous dysplasia. Therefore, we diagnosed her as having polyostotic fibrous dysplasia. At present, the left maxillary tumor has not progressed. We are continuing careful follow-up.

中咽頭癌において上側壁が切除された場合，術後にしばしば鼻呼吸，嚥下，構音障害をきたす。著者らはこのような欠損における再建にGehanno法を用い，術直後より良好な術後機能を得ている。今回Gehanno法の長期的成績について評価をおこない，同法の有用性につき検討をおこなった。1997年より現在までに33例に対しGehanno法を施行し，今回8例に対して，術後機能評価を行うことができた。それらの症例については概ね順調に術後機能の維持ができていると思われるが，前腕皮弁使用例の一部において，術後徐々に機能が悪化してくる症例があった。元来前腕皮弁は柔軟性に優れており，中咽頭のような複雑な形態の再建に適しているとされていたが，Gehanno法による再建材料としては，周囲組織の瘢痕による形態的変化を受けやすい可能性が示唆され，皮弁の第一選択としては腹直筋皮弁が推奨されると思われた。

Objective: Chemoradiation based on S-1, a novel oral antitumor agent of fluorinated pyrimidines, is the treatment for T2N0 glottic carcinoma; however, the optimal scheduling and dosing have still not been established. A phase I study was conducted to determine the maximum tolerated dose of S-1 with radiotherapy of 2 Gy/day for 5 days a week to a total dose of 60 Gy. Endpoints of this study were to examine the toxicity profile of this regimen and to determine the recommended dose of S-1. Methods: Concomitant administration with the above-mentioned radiotherapy of S-1 once a day for 2 weeks, beginning on the day therapy was started, followed by 2 weeks off the drug and 2 weeks on the drug with the dose escalating from S-1 60 mg/body (level 1) to 80 mg/body/day (level 2), and then to 100 mg/body/day (level 3). Results: Twenty-one patients were valid for safety. Eighteen patients were enrolled in the dose-escalation phase. In all patients, S-1 was administered. The maximum tolerated dose was determined to be 100 mg/body/day and the dose-limiting toxicity was indicated by the onset of grade 3 chemoradiation dermatitis. Therefore, the determined recommended dose of S-1 was 80 mg/body/day. Objective response according to Response Evaluation Criteria in Solid Tumors were observed in 20 of 21 patients who had measurable disease (95.2%). Conclusion: Concurrent S-1 and radiotherapy was feasible and well tolerated, and was suggested to produce a worthwhile response in T2N0 glottic carcinoma. These results warrant further investigation, and a phase II has already been started.

In this report, we provide evidence using a serial bone marrow transplantation (BMT) protocol that intra-bone marrow (IBM)-BMT (IBM-BMT) can efficiently reconstitute the hemopoietic system with cells of donor origin, in contrast to conventional intravenous (IV)-BMT (IV-BMT). Furthermore, the hematolymphoid system of secondary recipients that had received bone marrow cells (BMCs) from primary recipients treated with IBM-BMT recovered earlier than that of the secondary recipients of BMCs from primary recipients treated with IV-BMT. This was the case when the Lin-/c-kit+ progenitor cells of the secondary and tertiary recipients were examined. These findings indicate that IBM-BMT can facilitate the development of not only cells of various lineages but also the effective generation and, more importantly, the maintenance of the progenitor cells. Furthermore, we show that IBM-BMT can reconstitute the dendritic cell (DC) subsets (myeloid and lymphoid DCs), which are critical for the initiation of both adaptive and innate immune responses. The frequency of both myeloid and lymphoid DC subsets was approximately equal to that of normal age-matched untreated controls and, after second and third BMT, this ratio was close to that observed in the normal controls. However, the lymphoid DCs were clearly reduced in the secondary and tertiary recipients of BMCs from mice that had received IV-BMT. Therefore, the development of DC subsets is also normally maintained in the IBM-BMT group.

Warthin's tumor is benign and exclusively involves the parotid gland but may, however, often show multifocal and/or bilateral growth. The aim of this study was to evaluate the surgical procedure for removal of this tumor. Sixty patients with Warthin's tumor in the parotid gland who presented at the Kansai Medical University Hospital from 1990 to 1999 were the subjects of the present study. The surgical procedures were as follows. We performed enucleation for tumors in the deep lobe. Tumors in the superficial lobe were resected with partial parotidectomy, and an enucleative procedure was also performed at the bottom of the tumor where the tumor capsule directly touched the facial nerve. No recurrence was observed in all sixty cases including cases of rupture of the capsule before or during surgery. Therefore, we recommend that enucleation is a useful choice as a surgical procedure for the removal of Warthin's tumor after accurate detection of the tumors using MRI. The overall incidences of temporary and permanent facial nerve palsy were 19.7% and 0%, respectively. The incidence of palsy increased after surgery for multiple tumors or deep lobe tumors. These findings indicate that more careful consideration for preservation of the facial nerve should be given in such cases and that simultaneous surgery for such tumors in the bilateral parotid glands should be avoided to prevent bilateral facial nerve palsy.

The State-Trait Anxiety Inventory (STAI) test is a self survey method used to study a patient's anxiety status. In this study, we investigated the role of dizzy patients' anxiety psychology by analyzing the STAI. Subjects were 377 patients (141 male and 236 female) who complained of dizziness and visited the Department of Otorhinolaryngology at Kansai Medical University from August 2002 to July 2003.1, In the dizzy patients, State Anxiety (A-State) and Trait Anxiety (A-Trait) score showed significantly higher than in the controls. STAI score in female patients was significantly higher than that in male patients.2, In the same patients, A-State scores were decreased after patients showed improvement in their symptoms, however A-Trait score were not changed.3, The patients whose A-State and A-Trait scores in the first medical examination were very high(V) showed high A-State score even after absence of vertigo and dizziness.Based on these results, we concluded that STAI test was simple to use and might provide some helpful information for therapy of anxiety in dizzy patients.

We reported a patient with pseudogout associated with parathyroidectomy. A 68-year-old woman, diagnosed with primary hyperparathyroidism, presented with serum concentrations of ionized calcium. Patients with hypercalcemia have a high incidence of calcium pyrophosphate dihydrate crystal deposition into joints. Rapid drops in serum calcium levels can cause shedding of these crystals into synovial fluid which may precipitate acute attacks of pseudogout. Furthermore, the patient has diabetes mellitus. Diabetes mellitus inhibits insorption of magnesium which may cause high incidence of calcium pyrophosphate dihydrate crystal deposition into joints, too. It has been well established that acute attacks of pseudogout may be precipitated by parathyroidectomy and/or diabetes mellitus.

We present a patient with metastastic renal cell carcinoma to the ethmoid sinus. A 68-year-old male consulted with complaints of left epistaxis and nasal cavity tumor. His status was post left total nephrectomy for renal cell carcinoma. The histological diagnosis was renal cell carcinoma (clear cell type). We performed skull base surgery for total ethmoid sinus resection. We report on this case and discuss metastasis of renal cell carcinoma to the head and neck region.

The protective effect of dexamethasone (DEX) against noise-induced trauma, as reflected in hair cell destruction and elevation in auditory brainstem response (ABR) sensitivity, was assessed in guinea pigs. The animals were administered DEX (1, 10, 100, and 1000 ng/ml) or artificial perilymph (AP) via a mini-osmotic pump directly into scala tympani and, on the fourth day after pump implantation, exposed to 120 dB SPL octave band noise, centered at 4 kHz, for 24 h. Animals receiving DEX demonstrated a dose-dependent reduction in noise-induced outer hair cell loss (significant at 1, 10 and 100 ng/ml DEX animals compared to AP control animals) and a similar attenuation of the noise-induced ABR threshold shifts, observed 7 days following exposure (significant at 100 ng/ml DEX animals compared to AP control animals). These physiological and morphological results indicate that direct infusion of DEX into the perilymphatic space has protective effects against noise-induced trauma in the guinea pig cochlea.

A 39-year-old female was diagnosed with left acute otitis media and had paracentesis. Because she had continuous vertigo immediately after the paracentesis, she was sent to our hospital. At first she was treated with conservative therapy, but the severe hearing loss, dizziness and tinnitus worsened, so she underwent surgical exploration of the tympanic cavity 10 days after the onset. During the surgery, there was no dislocation of the ossicle, but perilymphatic leakage from the oval window was observed. The window membrane was repaired with temporal fascia and fat. Although her dizziness disappeared completely, her tinnitus persisted. However, the tinnitus disappeared with time and the hearing loss gradually recovered. This case was possibly a medical accident, but it is important to recognize that perilymph fistula is one of the complications of paracentesis, and when it occurs, it must be diagnosed accurately.

In the seismic design of nuclear power plant, it is recently considered to use probability method in addition to certainty method. The former method is called Seismic Probability Safety Assessment (Seismic PSA). In case of seismic PSA for some components of a nuclear power plant using a shaking table, it is necessary for some limited conditions with high level of accelerations such as actual conditions. However, it might be difficult to achieve the test conditions that a current shaking table based on hydraulic power system is intended for the test facility. Therefore, we have been planning out a test method in which both a current and another shaking table called a booster device are applied. This paper describes the verification test of a synchronized control between a current shaking table and a booster device.

We report a case in which mastoiditis caused meningitis with consciousness disturbance due to acute otitis media in patient with cerebral arteriovenous malformation (following AVM surgery), occurring 14 years after surgery.The patient was a 32-year-old, female. X-ray and CT scan of the mastoid showed clouding and a fusion image involving part of the mastoid cells on the affected side. A burr hole showed the presence of mastoid cells, and thus it was thought to be the route of infection.The patient underwent mastoidectomy. A bone defect was recognized in the middle cranial fossa, but there was no dura mater defect or leakage of cerebrospinal fluid observed. However, leakage of cerebrospinal fluid did later develop 12 days after the initial surgery. Craniotomy was performed over a wider area than that during the previous AVM surgery.An increase in the size of the cerebrospinal fluid fistula and in the degree of granulation was recognized in the osteotomy region and in the dura mater that had been incised during the previous AVM surgery. This case supports the findings of previous reports which indicated that factors such as inner ear deformity or duraplasty in an area behind acute otitis media may be related to intracranial otogenic complications. Craniotomy for AVM may be a potential route of infection for intracranial otogenic complications. The surgical method should thus be selected and managed carefully in order to avoid postoperative onset of such infections.

The MRL/lpr mouse, which is homozygous for the recessive lpr genes and has a mutation in the Fas gene encoding a cell-surface receptor for apoptosis, exhibits severe lymphadenopathy and develops systemic lupus erythematosus (SLE)-like disease. It has recently been reported that this mouse also manifests sensorineural hearing loss (SHL) with cochlear pathology at 20 weeks of age. We examined the effects of reconstituting severe combined immunodeficient (SCID) mice with MRL/lpr bone marrow on the development of SHL. These mice normally develop neither SHL nor cochlear pathology. Immune-mediated SHL and cochlear pathology did, indeed, occur following transfer of MRL/lpr bone marrow into SCID mice. These findings suggest that the development of SHL and cochlear pathology observed in MRL/lpr mice and in SCID mice receiving MRL/lpr bone marrow are the result of bone marrow defects rather than the result of a problem intrinsic to the cochlea.

Primary malignant melanoma of the nasopharynx is a rare disease with poor prognosis. There has been no established treatment for the disease.We report herein a case of a 75-year old man, who was referred with hearing impairment and nasal obstruction. Clinical examination demonstrated left middle ear effusion and nasopharyngeal mass. The histological examination indicated malignant melanoma. Magnetic resonance imaging (MRI) showed a gadolinium-enhanced mass on the left side of nasopharynx. Imaging studies could not detect distant metastasis. The patient received combined chemotherapy with DAV treatment (DTIC+ACNU+VCR), but there was no response. Intratumoral administration of Interferon-beta inhibited tumor growth and X-knife was also effective in significantly decreasing tumor size. These therapies may be helpful in the local treatment of malignant melanoma, thus improving the patient's quality of life.

The Groningen voice prosthesis can be successfully replaced using the back-loading system. We have attempted to minimize patient stress by developing a front-loading system that does not require insertion of the introducer via the tracheo-oesophageal shunt to the oral cavity or the mesopharyngeal anaesthetization regularly used with the back-loading system. Using our front-loading system, the existing prosthesis is removed, then the posterior portion of the replacement Groningen prosthesis is grasped by a pair of nasal forceps with a small jaw to make an acute angle and inserted into the oesophageal cavity through the shunt at a stroke. All 20 patients who underwent forward-loading replacement of a Groningen (n=17) or Blom-Singer (n=3) valve with a Groningen valve tolerated the procedure well and experienced no complications except, in some cases, for minor bleeding just after insertion of the prosthesis.The procedure was completed within 30 seconds.

To investigate the interaction between Ca 2+ and nitric oxide (NO) in inner hair cells of the guinea pig cochlea (IHCs), the extracellular adenosine 5′-triphosphate (ATP)-induced NO production and the effects of NO on ATP-induced increase of intracellular Ca 2+ concentrations ([Ca 2+ ] i ) were investigated in IHCs using the NO-sensitive dye DAF-2 and the Ca 2+ -sensitive dye Fura-2. Extracellular ATP induced an increase in DAF-2 fluorescence, which thus indicates NO production in IHCs. The ATP-induced NO production was mainly due to Ca 2+ influx through the activation of P2 receptor. l -N G -nitroarginine methyl ester, a NO synthesis inhibitor, enhanced the ATP-induced [Ca 2+ ] i increase in IHCs while S -nitroso- N -acetylpenicillamine, a NO donor, inhibited it. We conclude that NO inhibits the ATP-induced [Ca 2+ ] i increase in IHCs by a negative-feedback mechanism.

当教室では, 術後のQOLの向上を考慮し, 近年頸部郭清術の際, 症例に応じて頸神経を温存する術式を行ってきた。しかしながら, 頸神経の詳細な役割については不明な点が多い。今回, 23例に対し術中神経刺激を行うことにより頸神経の運動機能を検討し, また検査しえた術後1ヶ月の19例と, 術後1年以降の28例に対し肩周囲の感覚機能について評価し, 頸神経の役割, 温存の意義について検討を行ったので報告する。術中の電気刺激による検討では, 副神経刺激では全症例で僧帽筋の収縮を認めたが, 頸神経刺激では全症例に筋の収縮は見られなかった。術後の肩甲部の感覚機能における検討では, 頸神経温存により感覚機能が保存され, 頸神経は, 知覚神経としての機能を有するものと推察された。また長期に観察すれば, 頸神経切断例においても, 感覚機能が改善する可能性が推察された。

アルツハイマー病では中枢聴覚系の機能障害を示唆する症状を合併する場合が少なくない．また細胞変性等の病変が疾病脳の聴覚上行路各部位にも確認されている．本研究ではマウス脳のこれらの部位におけるコリン線維とムスカリン性受容体（m2，m3タイプ）の発現分布密度を測定した．聴覚上行路諸核で，これらコリン線維・受容体を介する情報伝達・変換が聴覚の伝達に一定の意義を有することが，本研究から強く示唆された．

Using multiple-site optical recording techniques, the spatiotemporal activity was observed in both the cochlear and vestibular nucleus in newborn mice. The optical responses were obviously enhanced by bath-applied strychnine. A quantitative analysis showed higher enhancements to occur in the cochlear nucleus than in the vestibular nucleus. Optical imaging enables us to visualize the spatiotemporal extent of the inhibitory receptive field after the application of strychnine.

This study demonstrates the attenuation of aminoglycoside ototoxicity by cochlear infusion of dexamethasone (Dex) using a microcannulation-osmotic pump delivery system. The results indicate that treating the cochlea with Dex both before and after kanamycin administration was more effective in preventing ototoxicity than Dex treatment only after kanamycin administration. A concentration of 1 ng/ml Dex showed the greatest protective effect on both kanamycin-induced threshold shift of the auditory brainstem response and outer hair cell survival. These results show that the Dex treatment attenuates both functional and structural damage of the inner ear from aminoglycoside toxicity.