Morphological vestibular changes caused by barotrauma were studied in guinea pigs. Animals were exposed to rapid decompression from 2 absolute atmospheric pressures (ATA) to 1 ATA, which causes inner ear barotrauma in the ginea pig. During decompression, spontaneous nystagmus was recorded, which consisted of irritative symptoms initially, followed by paralytic nystagmus. After pressure loading and observation to confirm the abscense of Preyer's reflex with vertigo, the animals were tested for caloric nystagmus using ice water and then sacrificed at varying intervals. Then, morphological changes in vestibular organs and the organ of Corti were studied.
Half of the experimental animals showed canal paresis on caloric testing.
Damage to the organ of Corti was severe while that to vestibular organs was very slight. Damage to the sensory cells of the vestibular organs was not clear on light microscopy, despite a partial collapse of labyrinthine membranes. Under scanning electron microscopy, local damage was observed in a portion of the crista ampularis of the semicircular canals. In this area, incomplete or complete disappearance of kinocillia and stereocilia, similar to that seen after rotatostimulation, was observed. However, no damage to sensory hairs was seen in the utricles and saccules.
The observed vestibular organ damage, resulting from inner ear barotrauma, suggested effects on endolymphatic flow.

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Orthostatic dysregulation (OD) generally implies a systemic condition indicating poor circulatory function resulting from autonomic imbalance, which usually appears in a rather young population at or around puberty, predominantly in females. This condition can be recognized from the results of a questionnaire which has been proposed and prepared by the Pediatric OD Study Group of Japan as diagnostic criteria for OD. Schellong testing has also been developed as a screening method to determine OD or orthostatic hypotension.
We carried out a survey and analyzed data collected with the questionnaire and Schellong test results among 152 young normal females ranging in age from 18 to 21 years in order to obtain the actual prevalence of OD in these subjects.
Among 152 young normal females, 39 (25.7%) were confirmed to have OD based on the questionnaire. Although orthostatic dizziness was relatively common in this series of young females, regardless of the presence or absence of OD (90/152, 59.2%), this symptom, which is listed as one of the 5 major items on the questionnaire, was much more prevalent in subjects with OD (37/39, 94.9%). Similar prevalence patterns for fatigability or unexplained tiredness were also found in subjects with OD (28/39, 71.8%) when compared with total subjects (55/152, 36.2%).
As for the positive rate of the Schellong test, subjects with and without OD showed 33.3% and 31.3%, respectively, and this difference was not statistically significant. There was, however, a highly significant difference in the fall in systolic pressure during the Schellong test procedure between subjects without OD and 10 subjects with OD in whom orthostatic dizziness frequently occurred.
Although it is often said that the clinical value of the Schellong test for assessing OD and other related conditions may be questionable because of its relatively poor specificity, our impression was that this test procedure may still be useful and applicable to assessment of OD or autonomic nerve dysfunction as a screening measure, since the test has the advantage of being simple enough to carry out in clinical practice.

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Extratympanic electrocochleography with click stimulation at 80 dBnHL was performed in 15 subjects with normal hearing (28 ears) during the glycerol dehydration test. Testing was performed before oral administration of glycerol (1.2 ml/Kg) as well as after 1, 2, and 3 hours. The mean electrocochleography response from 12 recordings was determined to obtain stable values.
Although some ear action potential (AP) amplitudes increased at 1 hour after administration, the AP amplitudes gradually decreased during the test. There were significant differences between before and at 2 and 3 hours after administration. Summating potential (SP) amplitudes increased slightly, but there were no significant differences between before and each time after glycerol administration. Negative SP/AP ratios gradually increased during the test, and there were significant differences between before and each time after glycerol administration.
Laterality of the glycerol-induced changes in 13 subjects having both ears tested was positive at 1 and 2 hours after glycerol administration, but the laterality had diminished by 3 hours after administration. It was thus reasonable to compare both ears at 3 hours after glycerol administration.

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Localization of epidermal growth factor receptor (EGFR) was investigated immunohistologically in 68 untreated patients with squamous cell carcinoma of the head and neck regions. These patients consisted of 16 with cancer of the lips and mouth, seven with mesopharyngeal cancer, six with epipharyngeal cancer, 15 with hypopharyngeal cancer, 10 with laryngeal cancer, 12 with maxillary cancer and two with other tumors (cancer of the auricle and cancer of the eyelid in one patient each). The patients consisted of 57 men and 11 women, with a mean age of 60 years. In cases with a normal oral mucosa, marked expression of EGFR was observed in the epithelial cell membrane, while expression decreased toward the luminal surface. Cancer cells also showed positive staining of EGFR in all patients, but the intensity of staining was inconsistent among them. Among the 32 patients in whom the staining intensity of EGFR was equal to or weaker than that in basal cells of the normal oral mucosa, 12 patients had lymph node metastasis. Twenty-eight of the 36 patients in whom the staining was stronger than that in the normal cells had lymph node metastasis, suggesting that overexpression of EGFR in carcinoma cells is a risk factor for lymph node metastasis of head and neck cancers (P<0.005). On the other hand, there were no obvious relationships between either the size or the degree of keratinization of the primary lesion and EGFR expression.

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The distribution, number, projections and nature of ganglia and ganglionic neurons in the feline larynx were investigated morphologically. Six to eight large oval or spindle-shaped ganglia (including 50-80 ganglionic neurons per ganglion) in rostral portions of the paraglottic spaces, four to six small spindle-shaped ganglions (containing 5-25 ganglionic perkarya in each ganglion) dorsal to the posterior cricoarytenoid muscles and one to three small elliptical ganglia (having 15-25 ganglionic cells in each ganglion) around the inferior laryngeal nerves were observed in the larynx. Each ganglion was covered with a fibrous capsule and ganglionic neurons with a diameter of 25-30μm totaled 600 to 800. Ganglionic neurons received projections from the dorsal motor nucleus of vagus, the superior cervical ganglion (SCG) and the nodose ganglion (NG) ipsilaterally. On the other hand, ganglionic neurons projected to SCG, NG, ipsilaterally and the laryngeal mucosa bilaterally with ipsilateral predominance. Ganglionic neurons showed acetylcholinesterase positive reactions, presumably parasympathetic. On immunocytochemistry, many vasoactive intestinal polypeptide (VIP) -immunoreactive (ir) neurons, and a few tyrosine hydroxylase (TH) -ir and substance P (SP) -ir cells were recognized in ganglions, but no calcitonin gene-related peptide (CGRP) -ir neurons were found. These VIP, TH, SP-ir neurons did not change after denervation of the ipsilateral superior and recurrent laryngeal nerves. Many VIP- and some TH-, SP-, CGRP-ir fibers were also observed around vessels and glandular cells. The present findings show that intralaryngeal ganglionic neurons not only have an endogenic cholinergic nature, but are also involved in local sympathetic and sensory nervous systems.

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It is very difficult to differentiate follicular adenoma from follicular carcinoma in thyroid follicular lesions. The authors investigated the biological behavior of these thyroid follicular lesions using immunohistochemical techniques.
Specimens taken from normal thyroid, 2 cases; follicular adenoma, 9 ; atypical adenoma, 7; and follicular carcinoma, 8; were observed.
Proliferating cell nuclear antigen (PCNA) is a marker of cellular proliferation. Nucleoli are also increased in number and move to the nuclear margin in cases of cellular proliferation. The PCNA labeling index was calculated by counting the number of PCNA-positive cells per 2, 000 tumor cells.
PCNA labeling indices were 0.025% in the normal thyroid, 1.41% in follicular adenoma, 5.73% in atypical adenoma, and 6.16% in follicular carcinoma, respectively. Nucleoli retaining rate of the tumor cells were 40.0% in follicular adenoma, 63.7% in atypical adenoma, and 71.8% in follicular carcinoma. Rates of nucleolus margination were 20.9% in follicular adenoma, 34.4% in atypical adenoma, and 36.0% in follicular carcinoma.
Changes in the basement membrane were morphologically classified into three groups as follows; membrane structure almost preserved (group I), partial discontinuity (breaks) (group II), and widespread absence of membrane structure (group III), based on immunohistochemical investigation of Type IV collagen. Group I was demonstrated in 8 cases of follicular adenoma and one case of atypical adenoma. Group II was observed in one case of follicular adenoma, 3 cases of atypical adenoma and 3 cases of follicular carcinoma. In addition, group III was noted in 3 cases of atypical adenoma and 5 cases of follicular carcinoma.
However, the p53 mutation was observed in only one of 24 cases. These results suggest that the correlation between biological and morphological findings in tumors is very important for the differential diagnosis of thyroid follicular lesions.

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Transiently evoked otoacoustic emissions (TEOAEs) from 16 normal human ears and 26 normal guinea pig ears were measured with the ILO 88 (ver 3.91). The following results were obtained:
1) In one animal ear, waveforms of TEOAEs were unchanged after administration of muscle relaxants, and showed reversible changes before and after asphyxia.
2) In 3 guinea pig and 2 human ears, the input-output functions showed a strong saturation at higher stimulus levels, when measurement of the highest peak-to-peak amplitude was used as the output energy.
3) Highest peak frequencies (HPFs) of TEOAEs were distributed at around 1 kHz in human ears but were concentrated around frequencies of 2 kHz to 3 kHz in almost all guinea pig ears.
4) Latencies of predominant TEOAEs in human and guinea pig ears were 9.26±1.89 msec and 2.37±0.47 msec, respectively. Endpoint times of TEOAEs were 16.37±1.79 msec and 5.74±1.10 msec, respectively.
Both indicators in human ears were 3-4 times longer than those in guinea pig ears.
From these results, we conclude that click-evoked TEOAEs can be detected even in guinea pigs. In addition, our measurements showed that HPFs of TEOAEs in guinea pig ears were higher than those in human ears, and that latencies and durations in guinea pig ears were much shorter than those in human ears. The higher HPFs of TEOAEs in guinea pig ears may be attributable to higher resonant frequencies in the middle ear than are found in human ears. The short latencies of TEOAEs in guinea pig ears may be related to travel time through the guinea pig basilar membranes.

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Middle ear adenomas are rare and difficult to diagnose. Recent histological studies suggest the presence of a distinct disease entity known as a middle ear adenoma.
A 16-year-old boy with a middle ear tumor was treated by partial temporal bone resection, and the tumor was removed by a combined method using the middle cranial fossa and infratemporal fossa approaches. Histological and immunohistochemical studies on this tumor showed the findings of a benign adenoma. Left facial palsy was noted postoperatively, but it subsequently recovered almost completely.

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Two-route infusion chemotherapy with a smaller dose of CDDP was applied for combined modality treatment with radiation therapy for head and neck cancer from 1985 to 1992. To determine the appropriate dose of CDDP in this treatment, we investigated parameters concerned with its toxicity by comparing two groups given 5 and 10mg of CDDP as a daily dose. Complete response was attained in 18 of 24 cases in the 5mg group and 8 of 11 cases in the 10mg group. The toxicity due to CDDP in this protocol was found generally to be slight in both groups. Among the parameters of toxicity, creatinine clearance was most affected. A decrease in 24 hr. creatinine clearance was noted in 15 of 29 cases in the 5mg group and 10 of 12 cases in the 10mg group. We had to discontinue this treatment after the first course because of lowered creatinine clearance in a patient in the 5mg group. Stomatitis due to radiation therapy appeared to become worse in combination with this chemotherapy. The 10mg dose of CDDP can be applied as a safe combination treatment with radiation therapy for head and neck cancer. To improve the outcome of this treatment modality for carcinomas of the tongue and oral floor, the 10mg dose of CDDP was thought to be more beneficial. However, in the case of cumulative doses of CDDP over 100mg, precaution should be taken to avoid the risk from the toxicity of more CDDP administration.

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Inverted papilloma on the sino-nasal cavity (IP on SN) is a rare benign tumor. However, local recurrence and distant metastasis do occasionally occur. The histogenesis and histological prospects for the biological behavior of this tumor are still unknown. To clarify these issues, we histologically studied 25 cases of IP on SN and 10 cases of IP on the urinary bladder (IP on UB), which were biopsied or resected in the National Shikoku Cancer Center Hospital. Since, with regard to aspects of histogenesis such as metaplasia, dysplasia and malignant transformation, there were some similarities and differences between these two benign tumors. Biopsied or resected specimens were microscopically examined with hematoxylin-eosin (HE), periodic acid-Shiff (PAS), and Azan stains.
Sixteen of 25 IP on SN presented a typical inward growth Pattern and 9 cases were simultaneously associated with an exophilic proliferation pattern. In cases of IP on UB, a typical inverted growth Pattern was observed in 3 cases. Seven of 10 IP on UB showed a complex of inward and exophilic patterns. Subsequently, we focused on metaplasia of IP, probably caused by certain physiological, chemical and inflammatory stimuli. All IP on SN bore squamous metaplasia and 5 cases simultaneously showed features of transitional metaplasia. Often, these two types of metaplasia were observed in the submucosal glands. In IP on UB, 7 of 10 cases showed squamous metaplasia and 9 cases presented intestinal metaplasia.
These metaplastic changes were also found in Brunn's nest. Furthermore, the metaplastic epithelium in 24 IP on SN demonstrated stratified proliferation, atypical nuclei and/or mitosis which were considered to be evidence of malibnancy. In fact, 9 of 25 IP on SN partially contained a component of squamous cell carcinoma and 7 cases out of 10 IP on UB showed features of transitional carcinoma in a portion of the papilloma lesion.
This evidence suggests that both IP on SN and IP on UB originate in submucosal glands, specifically exocrine glands in the sino-nasal region and Brunn's nest in the urinary bladder. Also, in these glands, metaplastic change was commonly seen, and occasionally revealed malignant features such as squamous cell carcinoma in the sino-nasal cavity and transitional carcinoma in the urinary bladder.
We finally concluded that the process of growth and the mechanism of malignant transformation might be similar between IP on SN and IP on UB and metaplastic change might play an important role in the maligant transformation of IP on SN and IP on UB.

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Nocturnal polysomnography (n-PSG) and diurnal polysomnography using diazepam (d-PSGD) were performed on 46 patients with sleep related breathing disorders including sleep spnea syndrome (SAS) patients and simple snorers.
Sleep stage, apnea type, and various indices of breathing disorders were examined, and the results obtained by the two different sleep studies were compared.
There were no significant differences in either the apnea type or the indices of breathing disorders between the two sleep studies.
Concerning the sleep stage, significant differences in the duration of REM sleep between the two sleep studies were observed.
In the duration of each stage of NREM sleep, however, there were no significant differences.
Also, no significant differences were observed in the indices of breathing disorders between SAS patients and simple snorers.
In conclusion: d-PSGD can be utilized as a substitute for n-PSG clinically, in patients with sleep related breathing disorders, as far as the study of NREM stages is concerned.

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