The purpose of this experimental study was to investigate the disseminating routes of viruses, bacteria, tumor cells and various substances along the trigeminal nerve sheaths. Thirty-four rabbits weighing approximately 3kg were used for this study. After an intraperitoneal injection of sodium pentobarbital, the left infraorbital foramen was exposed surgically. Then, various amounts of Indian ink solution were injected with a syringe driver for continuous microinfusion into the infraorbital nerve trunk at a rate of 0.03ml per minute. In all cases, during the appropriate state of general anesthesia, intravascular perfusion was performed with 10% folmaldehyde. The cranial and facial part of the rabbit were separated, decalcificated by Plank & Rychlo's method, dehydrated in an alcohol series, and embedded in 8% celloidin. Finally, 30 or 40 micrometer thick sections were stained with Hematoxilin-Eosin.
The following results were obtained: (1) The Indian ink injected into the infraorbital nerve trunk at the infraorbital foramen diffused along the infraorbital nerve and maxillary nerve, but did not reach the trigeminal ganglion. (2) The Indian ink diffused along the nasal branches of the infraorbital nerve and reached a point near the nose tip. (3) The small branches of the infraorbital nerve and its accompanying vessels penetrated the bony wall of the maxillary sinus, and the Indian ink reached the proper layer of the sinus mucous membrane.

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The bone mineral density of the internal auditory meatus was investigated by means of quantitative computed tomography (QCT) in 12 patients with acoustic tumor. Investigated portions of the internal auditory meatus were the anterior and posterior porus and the anterior and posterior fundus. The bony vestibule and cortical bone of the mastoid cavity were also investigated. The bone density values (calcium carbonate equivalent value) for each portion were analyzed statistically. Another investigation by CT program "Profile" revealed changes in CT values along the posterior wall of the internal auditory meatus, and the results were compared with that of the QCT.
The following results were obtained:
1) The highest calcium carbonate equivalent value was found in the posterior fundus, the lowest in the anterior porus. There were significant differences between the bilateral fundus and porus values.
2) There was a marked difference only in the anterior fundus of the abnormal side in comparison with the normal side, while differences in the other 5 portions were not statistically significant.
3) There were no significant differences in any of the portions between cases of superior vestibular nerve origin and those of inferior vestibular nerve origin.
4) In Profile, the CT values increased gradually from the porus to the fundus on both sides. A dip formation, indicating a lower CT value, was found between the porus and fundus in many cases. It was suggested that this dip formation was influenced by pneumatization of the posterior wall of the internal auditory meatus.

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The author succeeded in producing vestibular ganglionitis by inoculating herpes simplex virus type 1 (HSV-1) into the back of the auricle of a new-born mouse. Postural deviation to the inoculated side was observed in 14 of 275 mice (5.1%) 6 to 10 days after the inoculation. In 6 of the 14 mice (42.9%) with postural deviation, HSV antigens were demonstrated immunohistochemically in the vestibular ganglion cells of the inoculated side. No antigens were identified in the animals with normal posture or in controls.
Vestibular functions were evaluated in 5 animals suffering from postural deviation by the following test procedures. 1. behavior in an open field, 2. righting reflex, 3. transversing a narrow path, 4. ascending a rope, 5. negative geotaxis, 6. grasping a rod, 7. swimming. None could perform these tasks due to impairment of vestibular function. Histopathological and immunohistochemical examinations showed degeneration of the vestibular ganglion cells in 4 of the 5 mice, while HSV-1 antigens were recognized in 2 of them. The results of the present study show that inoculation of HSV into the back of the auricle of a new-born mouse can cause infection of the vestibular ganglion resulting in symptoms similar to those of vestibular neuritis, though the inci-
dence is low compared to that of facial paralysis.

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The expression of cytokeratin (CK) subclasses was immunohistologically investigated in normal laryngeal epithelia by the ABC technique using monospecific monoclonal antibodies. There are two types of epithelium in the larynx; squamous epithelium of the glottis and ciliated epithelium mainly of the supraglottis. A difference in expression pattern was observed between these two epithelia only in 3 CKs, specifically CK-8, CK-13 and CK-19.
In the glottis, CK-8 was negative in all layers, CK-13 was positive in the suprabasal and superficial layers, and CK-19 was strongly positive in the basal layer, but apparently reduced in suprabasal layers and completely negative in the superficial layers.
In the supraglottis, on the contrary, CK-8 was positive except in the basal layer, CK-13 was negative in all layers, and CK-19 was positive in all layers.
When ciliated epithelia were reduced to squamous metaplasia, the epithelial cells were morphologically similar to the squamous cells, and the CK xpression also showed the same pattern. In proximity to this squamous metaplasia, however, there were lesions whose cell type morphologically still resembled that of the ciliated epithelium, but whose pattern of CK expression had already been reduced to that of the squamous cell.

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A 6-years 9-month-old child with congenital severely hearing impaired received a Nucleus 22 channel implant. Twenty-two CG electrodes are now in use. In the 5 months since the cochlear implant, the patient has made good progress. Her vowel discrimination score has reached 100%. However, her consonant discrimination has remained at the chance level. On the other hand, auditory reception of environmental sounds has shown relative improvement. Problems encountered in pediatric use of the cochlear implant are also discussed herein.

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The anti-tumor effects of recombinant human interleukin-2 (rIL-2) and sizofiran (SPG) were evaluated individually and in combination in C57BL/6 mice intraperitoneally inoculated with EL4 lymphoma. The anti-tumor effects were evaluated by analysis of the intraperitoneal cell population in Giemsa-stained specimens, surface marker analysis of peritoneal exudative cells with flow cytometry, cytotoxic assay of cells against autologous tumor and Yac-1 lymphoma and a negative selection method, to identify the anti-tumor effector cells showing cytotoxic activity.
The administration of SPG and/or rIL-2 reduced the lymphoma cells and proliferating lymphocytes, resulting in a decreased tumor/lymphocyte ratio in the order:control mice>SPG-treated mice>rIL-2-treated mice>rIL-2 plus SPG-treated mice.
On day 5 after tumor inoculation, elevations in the number of L3T4⁺, Lyt2⁺, asialo GM1⁺ or Mac-1⁺ were demonstrated in the order:control mice<SPG-treated mice<rIL-2-treated mice>rIL-2 plus SPG-treated mice. The cytotoxic activity of peritoneal exudative cells against autologous tumor and the NK (natural killer) activity were increased in the same order.
The anti-tunor effector cells which showed cytotoxic activity against autologous tumor cells were cytotoxic T lymphocytes, NK cells and cytotoxic macrophages. In the mice treated with SPG and rIL-2 plus SPG, especially, cytotoxic macrophages were shown to be the main anti-tumor effector cells.
On day 10 after the inoculation, both a marked reduction in Lyt2⁺ lymphocytes and an elevation of L3T4⁺ lymphocytes were observed in all groups of mice. NK cells and cytotoxic macrophages were thought to be the main effector cells against autologous tumor, but their cytotoxic activities
were lower than those examined on day 5.
It was demonstrated that the administration of SPG and/or rIL-2 to the EL-4 lymphomabearing mice activated immune response cells in the peritoneal cavity such as T lymphocytes, NK cells or macrophages, which caused a reduction in lymphoma cells. The combination rIL-2 and SPG therapy was shown to activate the anti-tumor immune response at the tumor site more effectively than when either agent was administered alone.

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There are two types of cholesteatoma in children, congenital and acquired. The pathogenesis of each type is thought to be different. The pathogenesis of congenital cholesteatoma is thought to be the embryonic inclusion of squamous epithelium, whereas acquired cholesteatoma is thought to develop from various factors including recurrent otitis media and tubal insufficiency.
We reviewed a series of 23 patients with congenital cholesteatoma and 27 patients with acquired cholesteatoma, aged 2-15 years, who were operated on at our institution between January 1981 and December 1990. Planned staged surgery was performed in all patients. In the firststage operation, the canal-wall-up technique was used in all cases. About 12 months after the first operation, the second-stage operation was performed to investigate the course of the disease. The presence of recurrent and residual cholesteatoma was evaluated at this time.
In the congenital cholesteatoma series, 11 cases of residual cholesteatoma (48%) were detected at the second-stage operation. Since recurrent cholesteatoma was not observed in the series of congenital cholesteatoma cases, the prognosis of these cases was considered to be good.
On the other hand, in the acquired cholesteatoma series, 9 cases (33%) of recurrent cholesteatoma and 13 (48%) of residual cholesteatoma were detected at the second-stage operation. For the second-stage operation, the canal-wall-up technique was performed on 18 patients with no recurrence, whereas the canal-wall-down technique was used on all 9 patients with recurrence. Additional mastoid obliteration was performed on 7 of these 9 patients. The prognosis of the patients who underwent obliteration was good, and there was no recurrence of cholesteatoma after the second operation.
From these observations, it was concluded that planned staged tympanoplasty was useful for eliminating recurrent and residual cholesteatoma. It is also apparent that, in order to prevent recurrent cholesteatoma, it is necessary to reduce the air space to compensate for poor eustachian tube ventilation.

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Human papillomaviruses (HPVs) are associated with tumor lesions of the larynx. In order to develop a model for investigating the role of HPV in human laryngeal carcinogenesis, normal human laryngeal epithelial cells (HLEC cells) were transfected with a cloned full-length HPV genome. The HPV type 16 (HPV-16) most often associated with cancer of the larynx induced an extended life-span in vitro of HLEC cells by exceeding 100 population doublings, while the HPV-11 that is associated with benign laryngeal papillomas failed to do so. The extended life-span cells (HLEC-16 cells) contained integrated HPV-16 DNA, expressed viral E6 and E7 mRNA, showed anchorage-dependent growth and were non-tumorigenic. Using indirect immunocytochemical staining, nuclear p53 protein was not detectable in any of the HLEC-16 cells, implying that HLEC-16 cells were negative for p53 gene mutations. HLEC-16 cells should be useful for studying mechanisms involved in proliferation, differentiation and neoplastic transformation of HLEC cells.

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Perceptual study: Sixty-seven Japanese monosyllables were whispered by 12 normal speakers and tape-recorded. Listening tests by 24 normal listeners revealed that vowels, semivowels, nasals and fricatives were identified with excellent scores. Although voiced stop consonants were frequently judged as corresponding voiceless consonants, the difference in scores between the two groups was not statistically significant.
Acoustical study: The acoustical features of the samples uttered by the subjects who were skilled in whispering showed that first-formant transition plays an important role in discrimination between voiced and voiceless stop consonants.
Aerodynamic study: In the subjects who were skilled in whispering, intraoral air pressure was significantly higher in voiceless stop consonants than in corresponding voiced consonants.
As a result, it was suggested that the articulation score of whispering would be improved when uttered under acoustical and/or aerodynamic monitoring.

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Extratympanic electrocochleography and pure-tone audiometry were performed in unilateral Meniere's disease patients before and 1, 2 and 3 hours after oral administration of glycerol.
The mean electrocochleographic response from 12 recordings at 80 dBnHL click stimuli was determined to obtain stable values. The electrocochleographic response during the glycerol dehydration test was compared with that in normal subjects(28 ears). A positive result on a pure-tone audiogram was determined by an improvement of at least 10 dB in two octave bands.
In 25 involved ears with Meniere's disease, the action potential (AP) amplitudes gradually decreased during the test, but there were no significant differences. The summating potential (SP) amplitudes decreased during the test and there was a significant difference at 2 hours after administration. The negative SP/AP ratios were unchanged.
The Meniere's disease patients were classified into two groups; one with a positive response on the audiogram and the other negative responses including deterioration. According to multiple comparison testing, there were significant differences in AP amplitudes and SP amplitudes between the positive group and normal controls at 2 and 3 hours after administration, and between the positive group and the negative group at 3 hours. Electrocochleographic changes in the positive audiogram group were significant.
Then, the patients were classified into three groups by negative SP/AP ratio before administration. The first group consisted of negative ears whose negative SP/AP ratios were less than 0.36, which was the upper 95% confidence limit for 40 normal hearing ears, the second consisted of slightly positive ears (0.36_??_negative SP/AP ratio<0.40), the last consisted of severely positive ears whose ratios were more than 0.4, which was the upper 99% confidence limit. There was a significant difference for the SP amplitudes between the slightly positive group and normal controls at 2 hours after administration. Electrocochleographic changes in the slightly positive group with a negative SP/AP ratio were significant at this SP amplitude.
In 18 normal ears with Meniere's disease, electrocochleographic changes showed no significant difference. However, the SP amplitudes in 3 ears and the negative SP/AP ratios in 4 ears decreased to less than 80% of the pre-administration value, although they had not fallen below that in the normal controls. These decreases indicate that some normal ears with Meniere's disease already had the distinctive features of involved ears. Whether the fluctuation in hearing will appear in the normal ears with decreasing SP amplitudes or negative SP/AP ratios, as in the involved ears, remains to be determined.

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