We examined intracellular Ca²⁺ responses of nasal gland acinar cells in order to clarify cellular responses and molecular events with regard to the regulatory mechanism of nasal secretion. The acinar cells of the serous gland, in the guinea-pig nasal septum, were obtained by meticulous and selective dissection with minimal contamination of epithelial lining cells followed by collagenase treatment. The dispersed acini were incubated in an oxygenated solution supplemented with fura-2 acetoxymethyl ester and the intracellular Ca²⁺ concentration ([Ca²⁺] i) was measured using fluorescence ratio imaging microscopy.
The application of acetylcholine (ACh) to the nasal gland acinar cells induced an initially rapid increase in [Ca²⁺] i followed by a sustained plateau. The increase in [Ca²⁺] i induced by ACh was concentration-dependent and ranged from 10^-8 to 10^-5M. The intracellular Ca²⁺ response was completely inhibited by atropine, indicating the presence of muscarinic cholinergic receptors. Removal of external Ca²⁺ with addition of EGTA resulted in a transient increase without a sustained phase. The sustained phase of the [Ca²⁺] i increase induced by ACh was inhibited by Ni²⁺, but not by nifedipine. The initial phase seems to be due to mobilization from cytosolic Ca²⁺ stores while the subsequent sustained phase is dependent on the influx of external Ca²⁺ ions sensitive to Ni²⁺.
We have demonstrated that increasing the Ca²⁺ gradient by elevating external Ca²⁺ accelerates Ca²⁺ entry, and that depolarization of cells due to elevated external K⁺ attenuates Ca²⁺ entry. These findings suggest that the Ca²⁺ entry process in nasal gland acinar cells is dependent on the electrochemical gradient across the membrane. External alkalization from 7.4 to 8.4 resulted in a further elevation of the sustained phase. On the other hand, external acidification from 7.4 to 6.4 had inhibitory effect on the [Ca²⁺] i increase. It is suggested that resposed by alteration in the external surface charge or extracellular H⁺ was competed with extracellular Ca²⁺ in the Ca²⁺ entry.

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Optokinetic afternystagmus, or OKAN, was investigated in 147 normal subjects (69 males and 78 females aged 20-78) for the purpose of obtaining the normal duration range and total number of beats in OKAN of the 1st. phase. OKAN was recorded nystagmographically with the eyes open in darkness immediately after the sudden cessation of horizontal optokinetic stimulation with a constant speed of 60 degrees/sec. for 45sec.
The duration data for OKAN of the 1st. phase were distributed in a very wide range, between 0 and 180sec., in all 294 samples. Therefore, the author arbitrarily divided the times into 3 categories: hypo-response with a duration below 10sec., middle response above 10sec. but below 60sec. and hyper-response above 60sec.
OKAN were classified into 6 groups. with 3 subgroups, based on durations of OKAN of the 1st. phase, as results varied widely.
1. Classified OKAN groups and their rates: symmetric bilateral middle response (1a) was 10.9%, asymmetric bilateral middle response (1b) 15.0%. symmetric bilateral hyper-response (2a) 2.7%, asymmetric bilateral hyper response (2b) 1.4%, bilateral hypo-response (bilateral no response (3a) and others (3b)) 25.2%, unilateral hypo response with contralateral middle response (4) 31.3%, unilateral hypo-response with contralateral hyper-response (5) 4.1%, and, unilateral middle response with contralateral hyper response (6) 9.5%.
2. Classified OKAN groups for each sex and in different age groups: Generally, characteristic changes in the rate of classified OKAN for each sex and in different age groups could not be detected, for example, bilateral hypo-response (3a and 3b) appeared in all age groups from different decades.
3. The mean value of the maximal velocity in the slow phase of OKAN of the 1st. phase was 8.6 degrees/sec, the mean value of the total number of beats in OKAN of the 1st. phase was 22.8 and the average durations of OKAN of the 1st. phase, to the right and to the left, were 27.3sec and 21.7sec., respectively.
OKAN of the 2nd phase appeared in 9 (6.1%) but OKAN of 3rd phase was not observed in any of the subjects.

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Rosenhall reported the polarization of kinocilium of otolith organs in the avian inner ear by LM. However, the otolith lagena, which is called the third otolith organ, is not well known, especially in terms of the 3-dimensional relationship between each maculae (utricular maculae, saccular maculae, maculae of the otolith lagena), the details of the striola and otoconial layers, and so on.
Therefore, the author conducted a study to clarify these points using 20 Columba Domestica pigeons (40 ears), under the rules for animal experiments established by Nihon University School of Medicine.
The pigeons were divided into 4 groups, 1. observations of the membranous labyrinth with binocular microscopes, 2. histological examination of serial sections of inner ear, 3. observations of the otolith lagena by SEM, 4. computer-aided 3-dimensional reconstruction of the membranous labyrinth.
The following results were obtained. 1. the mean angle between the utricular maculae and maculae of the otolith lagena was 31° (n=3), the mean angle between the saccular maculae and maculae of the otolith lagena was 45° (n=3). 2. striola of the otolith lagena demonstrated a C form and the kinocilium exhibited an orientation identical to that of the striola of the outer saccular maculae. 3. the otolithic membrane of the otolith lagena demonstrated a mesh form and the otoconial layer was observed to be thin above the striola. 4. the surface area of the maculae of the otolith lagena was 0.98mm² (n=3) and the number of sensory cells was 16, 800 (n=3).
The author also considered the functions of the otolith lagena.

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Surgical treatment of petrous cholesteatoma that involves the petrous pyramid and extends beyond the internal auditory canal is often difficult because of the site and extent of the cholesteatoma. Various problems pertaining to the operation are discussed from our experience with fourteen patients who underwent surgery in our hospital.
When accompanied with otorrhea, the middle ear was eradicated by radical mastoidectomy before total removal of the cholesteatoma in order to avoid intracranial infection. Staging operation was conducted in 6 patients in which otorrhea could not be stopped by conservative treatment. The surgical approach was translabyrinthine in 10 patients, middle cranial fossa plus transmastoid in 2, and a combination of these methods in 2. The postoperative large cavity was totally exteriorized in 5 cases in which eradication of the cholesteatoma was deemed too risky, although the exposed internal auditory canal and the denuded dura were supplemented locally. In the other 9 cases, the cavity was obliterated with abdominal fat and/or muscle flap. Facial nerve palsy was present preoperatively in 11 patients. They were treated by decompression in 7 cases, nerve-anastomosis in 2 and nerve grafting in one. In one patient, atrophy of the nerve was too severe to perform nerve grafting. Plastic surgery, such as suspension of the eyelid and masseter muscle transfer, was additionally carried out in 6 of the above patients. Postoperative follow-up study with CT and MRI is very important. In 3 of our cases, the cholesteatoma recurred and the reoperation was needed.

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Photodynamic therapy (PDT) is an innovative treatment involving the use of a photosensitizer and low powered laser to selectively destroy tumor cells. In the head and neck, its application to laryngeal papilloma. metastatic tumor and oral cancer have been reported but our report on PDT for laryngeal cancer is the only clinical report in Japan. At present, we treat laryngeal cancer by PDT using argon and excimer dye lasers such as the HpD. In the present study, we assessed the utility and safety of PDT and investigated long-term prognosis after this therapy. The subjects were 12 patients with laryngeal cancer who underwent PDT between February 1988 and October 1993. Among them, ten with cancer of the vocal cords underwent PDT as the primary treatment and two underwent PDT because of recurrence after radiotherapy. Under local anesthesia, PDT was performed using a video endoscope (Pentax EB2000). The optimal dose from an argon dye laser was set at 200-500mW/cm² of continuous waves for 20 minutes and that from the excimer dye laser was set at 200J/cm² of pulse waves (3-4mJ/pulse, 30-40Hz). The argon dye laser used was the Fujinon PDT developed by Fuji Photo Optical Co., Ltd. The excimer dye laser used was a product of Hamamatsu Photonics Co., Ltd.
1) Effect of PDT
The effect of PDT as a primary treatment for ten patients was classified as CR in eight and PR in two cases, the CR rate being 80.0%. When evaluated only for T1 patients, the results were classified as CR in eight and PR in one. The patient whose response was classified as PR had refused repeated PDT. CR was maintained for five and 13 months in the two patients who underwent PDT as a secondary treatment after radiotherapy. CR was obtained in 83.3% of all patients studied.
2) Duration of the effect of PDT and long-term prognosis
The patients were followed up for 14 to 71 months. The longest duration of CR achieved by PDT monotherapy was 65 months. Among the patients who underwent PDT as a sprimary treatment, one developed local recurrence and underwent radiotherapy. However, the prognosis was uneventful in all other patients. CR after PDT monotherapy was maintained for 42 months in one T3 patient. Two patients with a history of previous treatment thereafter relapsed and underwent total laryngectomy. The larynx could be conserved in 83.3% of all patients. However, it could be conserved in 100% of patients who underwent PDT as a primary treatment. When the prognosis of laryngeal cancer was investigated in all patients, two deaths from other causes, that is, leukemia and esophageal cancer, were confirmed, but there were no patients who died from the primary disease. Based on the results presented, PDT may be as effective as conventional therapies for early laryngeal cancer.
3) Adverse reactions and complications of PDT
Photosensitivity occurred in all patients, but required no therapy or other intervention. Laboratory tests for liver, renal and bone marrow function revealed no abnormal values attributable to PDT. There were no adverse reactions of clinical relevance and patients with severe complications and elderly patients were also treated safely with this therapy.

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A statistical analysis was performed in patients with press-through-pack (PTP) foreign body in the esophagus encountered in the Department of Otorhinolaryngology, Tohoku University School of Medicine. from 1986 to 1993. Furthermore, the radiolucency of PTP and the possibility of mucosal injury of the esophagus by PTP were examined by experimental methods. We obtained the following results:
1) The incidence of PTP foreign body in the esophagus increased in the period from 1986 to 1994 as compared with that from 1978 to 1985.
2) PTP foreign body was lodged in the following area: cricopharyngeal narrowing>bronchioaortic narrowing>hiatal narrowing.
3) Fluoroscopy with or without contrast material and flexible endoscopy were useful tools for diagnosis.
4) Direct esophagoscopy revealed mucosal erosion, hematoma, edema and intact mucosa in 14, 3, 3, and 6 patients. respectively.
5) The period of hospitalization was longer in patients with mucosal erosion than in those with intact mucosa.
6) The base of PTP made of aluminium could be detected as a radiopaque material by lateral projections, suggesting that PTP foreign bodies require roentgenograms made pararell to the base of PTP.
7) Histological study indicated that traumatic lesions in the extracted esophagus manually produced by the sharp corner of PTP were present in the mucosal layer and partially in the submucosal layer, suggesting that esophageal perforation by PTP was generated by additional factors such as secondary infection and iatrogenic trauma induced by esophagoscopy.

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Precision and problems in interpretation of results obtained by acoustic rhinometry (AR) in cases of mass lesion in the nasal cavity were evaluated with two models, a simple tubal model and a model based on the cast of a cadaver's nasal cavity (cadaver model), and with a human subject. A simple tubal model of 2cm inside diameter was used. Spherical claies with volumes of 1, 2, 3, and 3.5cm³. located at same point in the tube, were measured by AR, and a high correlation was found between the clay volume calculated by AR and the real volume of the clay (r=0.996). But the peak of decrease on the acoustic curve caused by clay was seen a bit posterior to the point where it was actually located. In the entire segment posterior to the peak on the acoustic curve, the value of the area was shown to be smaller than the value of the control. And the larger the volume of clay, the greater the degree of decrease in this segment. In the study using the cadaver model, a pill (0.3cm³) was put at nine sites in the nasal cavity, and AR was performed in eath case. The results were compared with the control curve. The decrease in the area on the acoustic curve corresponding to the site of pill placement was recognized, as in the simple tubal model study, and a decrease in the area in the posterior segment of the acoustic curve was also observed. When a small cylindrical foreign body was put at the center of the common nasal meatus of a subject, AR was performed ten times each before and after removal. The results were evaluated statistically, and the value of the area in the posterior segment, which was supposed to correspond to the cavity posterior to the foreign body, showed a significant increase after removal in comparison with the value before, as was shown by the model studies. The presence of a mass lesion might affect the course of the acoustic pulse, and the amount of sound volume reflected from the posterior cavity to the mass lesion is considered to be less than could be expected in theory. The results obtained by model studies revealed that it is impossible to diagnose the correct site of a mass lesion in the nasal cavity, especially its vertical dimension. But with AR even a fairly small mass lesion could be detected and its distance from the entrance of the nasal cavity diagnosed. We confirmed that AR enabled us to determine sites of mass lesions in the nasal cavity to a certain extent. But we have to be careful in interpreting the value measured by AR, especially the value of the posterior cavity to the mass lesion, because in some cases the value may differ from the actual value.

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Ambient pressure changes are known to induce vertigo and bodily disequilibrium, e.g. alternobaric vertigo. It is predicted, based on clinical observations of such vertigo, that the rates of pressure change are responsible for alternobaric vertigo. The aim of the present study was to clarify the influence of the rates of pressure change on the activities of primary vestibular neurons using an animal model of alternobaric vertigo. The responses of primary vestibular neurons to middle ear pressure stimuli were investigated in guinea pigs under 2 different rates of pressure change (±50, ±100mmH₂O/sec). The following results were obtained.
1. The response rates and the gains of firing rates with pressure stimuli were larger under ±100mmH₂O/sec than under ±50mmH₂O/sec.
2. The onsets of responses to pressure stimuli were faster under ±100mmH₂O/sec than under ±50mmH₂O/sec.
The results obtained in the present study reveal that vestibular activities are altered by the rates of ambient pressure change.

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By making several improvements in current hearing aid earphones, a new earphone (NC-3) for CM measurement in electrocochleography (ECochG) has been developed. A silicone tube with a 1.5mm inside diameter, 175mm in length, was attached to the acoustic hole side of the earphone. The earphone proper was shielded with aluminum foil and one end of the foil was connected to a low noise cable.
Human forearm was used as a dummy ear and the electrode HN-5 was fixed thereon, and a sound stimulus of 90dBnHL was delivered by the earphone (NC-3). No measurable artifacts, such as electromagnetic conductions and the CM-like mechanical vibrations generated by the acoustic output system, were recorded. By placing the earphone (NC-3) from a right-angle to a diagonal direction toward the electrode circuit, electromagnetic conduction contamination was prevented.
With an extratympanic procedure using the electrode HN-5, ECochG-CM was recorded from normal hearing subjects in both a shielded sound-proof room and a non-shielded ordinary but quiet room. Short tone bursts at 1 and 4kHz were employed as acoustic stimuli and delivered by the earphone (NC-3). In the non-shielded quiet room, no electromagnetic conduction contamination or mechanical vibration was observed and there were no differences in CM responses between the two rooms.
These results suggest that this earphone (NC-3), making CM recordings possible at the ordinary bedside without shielding, may contribute significantly to the subsequent spread of ECochG-CM measurement, by compensating for the disadvantages of a loudspeaker.

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Between 1970 and 1994, 60 pediatric cases, with 81 ears found to have dip type sensory neural hearing loss based on the appearance of an audiogram, were reported to the Department of Otorhinolaryngology at Iwate Medical University.
These findings were clinically evaluated and compared to adult findings.
The following results were obtained;
1) The dip type hearing loss was commonly seen among boys.
2) Approximately 25% were due to acoustic trauma, while 75% were of unknown origin.
3) Out of the 81 ears, 74 (91.4%) had a 4kHz dip.
4) An 8kHz drop indicated “abrupt type” hearing loss.
5) Many fathers of the children with dip type hearing loss were also found to have a hearing disorder. Among these fathers, many were found to have a dip type hearing loss similar to that of their children.
6) There were no differences in the clinical findings of dip type hearing loss between the adult and pediatric cases. Thus, the adult form is essentially equivalent to that in children.
7) Since dip type hearing losses were found mostly in the male group, it was assumed that a hereditary factor is involved.

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Sinusitis has been reported to be one of the major causative etiologies of olfactory disorder. According to our data during last 3 years, 47.5% of all cases of olfactory disorder were attributed to sinusitis. Persistent olfactory disturbance was often critical even after resection of the pathological sinus mucosa by surgery for chronic sinusitis. Accordingly, olfactory epithelial inflammation involved in sinusitis may be considered another important causative factor disturbing the restoration of olfactory acuity. To elucidate this hypothesis, the following experimental and clinical studies were carried out.
(1) A morphological study was done with specimens taken from the olfactory cleft of rabbits with experimentally induced sinusitis to analyze the inflammatory effects, and the degree of inflammatory damage was compared, histopathologically between olfactory and respiratory epithelium. SEM observation in the morphological study showed delayed healing in the olfactory portion in comparison with the respiratory portion (p<0.01). Cell proliferation activity as determined by immunohistochemical study with bromodeoxyuridine (BrdU) was significantly greater in the respiratory area of the cases with sinusitis than in the control (p<0.01). Cell proliferation status may play a significant role in this delay.
(2) Olfaction tests were performed in patients with sinusitis accompanied with olfactory disturbance. In addition to both T&T olfactometry and intravenous olfactometry using fursultiamine (Alinamin Test), Smell Identification Test (SIT) and Threshold Test by graded Phenyl Ethyl Alchol (PEA) were applied to estimate the olfactory acuity of the patients with sinusitis. The results of SIT and PEA tended to parallel not the Alinamin Test but T&T olfactometry. Results showed that the olfactory disorder caused by sinusitis tended to be severe. The results showed that the epithelial factor is important in explaining olfactory disorder etiologically in cases of sinusitis. In particular, olfactory disturbance tended to persist.

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