Metastasis of cancer starts with the penetration of cancer cells through the membrane surrounding the cancer focus into the stroma (extracellular matrix). The focal membrane consists of mainly type-IV collagen. An immunochemical study of 28 patients with benign thyroid nodular diseases and 27 patients with papillary carcinoma revealed the fragmentation of type-IV collagen in 4 patients with papillary carcinoma, Matrix metalloprotease (MMP)-2 and MMP-9 are the major enzymes which decompose type-IV collagen, and they have been suggested to be related to cancer metastasis. Therefore, we conducted biochemical and immunohistochemical studies to determine the relationship between these MMPs and the degree of malignancy in thyroid diseases.
The concentration of MMP-2 in the serum of patients with papillary carcinoma and patients with benign nodules was526.0±96.6and522.7±114.6ng/ml, respectively, and that of MMP-9 was53.8±40.3and39.9±36.0 respectively. There was no significant difference between the two groups in the concentration of either enzyme. The concentration of TIMP-2 in the serum was below the detectable level. On the other hand, the concentration of MMP-2in the tissue of papillary carcinoma, benign nodules and normal tissue was12.1±8.1, 5.7±4.3, and0.6±0.5ng. mg tissue protein respectively, and that of MMP-9 was 4.2±4.1, 2.1±1.7, and0.4±0.3ng/mg tissue protein, respectively. Concentrations of both enzymes were significantly higher in the papillary carcinoma tissue. Immunohistochemical studies revealed a diffuse granular distribution of MMP-2 in the cytoplasm of the tumor cells.
These findings imply that MMP-2 and MMP-9 are related to the degree of malignancy of cancer, especially metastasis.

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Introduction
Oxygenation at high pressure (OHP) is thought to be useful, even though regional blood flow is decreased, because increasing dissolved oxygen prevents the death of nerve tissue. In this report, we retrospectively investigated the effect of OHP on sudden deafness. Object and Method
We reviewed 522 patients treated with OHP at Kagawa Rosai Hospital over a ten-year period (January 1989 to December 1998). We discussed some prognostic factors: comparison between cases which had been treated with OHP previously and those which had not, number of days between onset and beginning of the treatment which included OHP, age. initial averaged five frequency hearing level, vertigo, tinnitus, complications of OHP, cases of
relapse and the time of the onset, which is about season, month and week. OHP was administered at a pressure of 2.5 atmospheres for 80 minutes a day from 10 to 15 times. All patients also received a course of intravenous administration of steroid, vitamin B12, Prostaglandin E1, ATP, and lowmolecular dextran. Results
Overall, complete recovery occurred in 19.7% of the patients, definite improvement in 34.9% (complete recovery included), and slight improvement in 58.1% (definite improvement included). Most of the patients (78.0%) were referred by other hospitals, because our hospital was the only one in the Sikoku area which had a big equipment of OHP. All 161 patients had already been treated in other hospitals over 8 days, but they had shown little improvement after the initial therapy. Of this group, complete recovery after the second course of teatment occurred in 13.0%, of the patients, definite improvement in 19.3%, and slight improvement in 39.1%. OHP was thus effective for about 40% of patients who had been unresponsive to the initial therapy.
Delay in treatment usually produces poor hearing recovery. There was a significant difference between those patients treated within 14 days and those treated 15 days or more after onset. The improvement rate also decreased with age. The prognosis of patients with vertigo was worse than those without vertigo. Tinnitus had no influence on the prognosis. There were no severe complications during the course of OHP, but otitis media with effusion occurred in 90 patients, and paracentesis was performed for 53 patients. Conclusion
The treatment of sudden deafness with OHP has been discussed in this report. Important prognostic factors were time between onset and beginning of the treatment which included OHP, age, vertigo, and the initial averaged five-frequency hearing level. We conclude that OHP should be performed within 14 days from onset, and that OHP was able to achieve hearing improvement in many cases unresponsive to the initial therapy if it was performed very early.

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A balloon has been developed that completely fills the choana, preventing water from leaking into the pharynxeven when the water is entering into the nasal cavity at a rate of 1000ml per minute. The balloon enables endoscopic sinus surgery (ESS) to be safely performed in "flowing water" This surgical technique is similar to that used in transurethral resections of the prostate because the tip of the endoscope is kept clean, and blood, debris and resected tissues are continuously removed by the water flow.
In addition, the water pressure helps to suppress bleeding. This technique enables ESS to be performed with greater ease and efficiency.
We have performed ESS in flowing water on 38 patients with chronic sinusitis under local anaesthesia. No complications, such as water leakage into the pharynx, were encountered, and only a few patients felt discomfort from the insertion of the balloon. Even if the balloon had burst, an emergency could have been easily prevented by withdrawing the endoscope from the nasal cavity and stopping the flow of water.
Ultrasonography (USG) was used to examine the water-filled nasal cavity during surgery (SSD-2000 and Micro Tip Radial [ASU-101]; Aloka, Ltd., Japan). Using USG, the middle turbinate, the inferior turbinate and the nasal septum could be visualized in a single coronal image. When the sensor was in the posterior ethmoid sinus, the orbit and its optic nerve could also be visualized. Since this surgery is performed under local anesthesia, eye movements can rapidly alter the position of the optic nerve. Thus, visualization of the optic nerve's exact position is extremely important.
Unfortunately, USG is not very useful for localizing structures and guiding the surgeon to distant tumors or cysts located behind thick bones, since ultrasound can not penetrate hard masses or bones. In this situation, navigation systems are more reliable than USG. Nevertheless, USG is often useful for depicting surgical sites, especially during a crisis, if the medial wall of the orbit is thin or if the skull base has been broken, exposing the dura. USG can also provide early warning of an impending complication.
USG also has several practical advantages over navigation systems: the cost of USG is much lower, preparation for surgery is unnecessary, visual information can be obtained in real time, and measurement accuracy (estimated to be about 2mm for navigation systems) is not a consideration. Thus, USG can be easily used to avoid complications in most surgeries for chronic sinusitis.
Flowing water also allows the nasal eavity to be completely washed and sterilized at the end of the surgery. This not only prevents post-operative infection, but enables sinus function to be more quickly recovered. In addition, the pressure from the balloon also prevents post-operative nasal hemorrhaging. This allows patients to be safely discharged from the hospital at an earlier time.
The balloon can also be used for non-surgical purposes. For example, emergent epistaxis can be easily stopped by the insertion of this balloon, even if the doctor is not an otorhinolaryngologist. In addition, the balloon's soft pressure allows it to be left in the nose for long periods without any complications.
We conclude that this simple balloon, which we have named the "Noda Balloon", is extremely useful for nasal treatments.

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Between June/1986 and June/1999, we treated 18 cases of previously untreated metastatic carcinoma in cervical lymph nodes from an unknown primary tumor. Among them, 15 cases were squamous cell carcinoma, 2 were adenocarcinoma, and one was undifferentiated carcinoma.
The dose of radiotherapy, which was planned only for the cervical lymph nodes, was 60-70Gy at the metastatic sites. Preventive radiotherapy at possible primary sites was performed only in one case. After these treatments, a primary lesion appeared in only two cases: in one case a tumor was found in the hypopharynx, and the other, which had been diagnosed as undifferentiated carcinoma, proved to be malignant lymphoma. Outcomes were analyzed except for these two cases.
The five-year survival rate was 31%. The loco-regional control rate was 57% after radiation treatment limited to the affected cervical lymph nodes. Distant metastasis appeared more often in open biopsy cases than in those receiving fine-needle aspirations (FNA).
According to these results, teratment of possible primary sites may not be necessary, and for initial pathological diagnosis, FNA is recommended, while open biopsy should be avoided, if possible.

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Quick change of the interaural time difference (ITD) generates moving sound stimuli. Specific biphasic eventrelated potentials called "time-shift evoked potentials (TSEPs)" can be recorded when this moving sound is given.
The results of TSEPs in various types of hearing loss were analyzed in comparison with auditory brainstem response (ABR) and slow vertical response (SVR) in order to evaluate clinial applicability of TSEPs. Firstly, the detection threshold of TSEPs was established in groups of patients with low tone sensorineural hearing loss and with steep high tone sensorineural hearing loss. The usefulness of TSEPs was then evaluated in patients with retrocochlear hearing loss and with functional deafness.
The patients with retrocochlear hearing loss were divided into 2 subgroups, one with auditory nerve disorder and the other with cortical disorder. It was found that TSEPs participate in the transference of auditory timefactors. They reflect the function of not only the auditory nerve and brainstem which form major components of ABR, but also the central nervous system superior to the inferior colliculus. TSEPs could be recorded in most patients with functional deafness and are more useful for its diagnosis than using the conventional directional hearing test. It is concluded that TSEPs is useful as a clinical test for detection of cortical disorder and functional deafness.

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We investigated the influence of ovariectomy on the salivary glands. Thirty-six rats received ovariectomies at the age of 15 weeks, and removal of parotid, submandibular and sublingual glands at the ages of 18, 21, 25, 27, 33, and 39 weeks. The weight of each gland and the total body were measured, Histological examinations noted the point of fatty degeneration. Twelve female rats were used as controls, each gland being observed at the age of 19, 28. and 41 weeks.
Body weights of the ovariectomized rats were greater than those of the controls, but neither the weights of the parotid gland nor the submandiblar sublingual gland were different. Fatty degeneration was observed only in the parotid glands and it increased gradually. There was no change in the parotid gland of the control group.
The ratio of the area of fatty tissue showed a statistically significant increase over time.
These results suggest that the parotid gland requires ovarian hormone to maintain its tissue.

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For 87 male and 100 female patients (average age of 58.5 years) with throat discomfort, we investigated the relationship between the intensity of annoyance caused by throat discomfort and psychological distress. We asked patients to assess their throat discomfort using a 100mm horizontal visual analogue scale (VAS) which defined the left end (0) as no annoyance and the right end (100) as overwhelming annoyance attributed to throat discomfort.
The extent of their psychological distress was evaluated by 3 tests: Cornell Medical Index-Health Questionnaire (CMI), Self-rating Depression Scale (SDS) and Self-rating Questionnaire for Depression (SRQ-D).
Our results indicate that the increase in intensity of annoyance caused by throat discomfort was significantly related to the increase in somatic symptoms (Spearman's ρ=0.164, P=0.025), symptoms connected to autonomic nerve dysfunction (ρ=0.203, p=0.006) as measured by CMI and neurotic condition as classified by Fukamachi's diagnostic method for CMI (p=0.049 by Kruskal-Wallis test). The increase in intensity of annoyance caused by throat discomfort was significantly related to the increase in depressive condition as measured using SRQ-D (ρ=
0.263, p<0.001), but not to that measured using SDS (ρ=0.097, p=0.185).
The results obtained from the present study indicate that VAS is a useful tool for measuring annoyance caused by throat discomfort, yielding valuable information about the intensity of patients' somatic and psychological complaints.

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We have recently been confronted with refractory upper respiratory infections with an increasing prevalence of penicillin (PC)-resistant S. pneumoniae There has been a broad consensus that acute otitis media (AOM) is caused by migration of pathogens from nasopharynx and proliferation in the middle ear space, and thus it is, very important to study the bacterial environment in the nasopharynx as the source of middle ear infections.
Eighty pneumococcal isolates from the nasopharynx of children with acute otitis media were evaluated by polymerase chain reaction (PCR) for mutation of Pcbinding protein (PBP) genes. The results showed mutation of all three PBP genes, pbp la, pbp 2x. and pbp _2b, in 30% of the isolates, while 74% were found to possess various PBP gene mutations, mostly in one-year-old children. Of the 46 isolates whose minimum inhibitory concentration (MIC) of Pc was≤0.06μg/mL. 43% were found to possess a pbp 2x mutaion, which affects cefem resistance. We genotyped each pneumococcal isolate from the nasopharynx of children with recurrent AOM by pulsed field gel electrophoresis (PFGE). In 9 of 11 pairs (82%) of consecutive AOM episodes, the nasopharyngeal isolate in the second episode was different. In addition, discrimination of each isolate based upon the mutation profile of its PBP genes in 8 pairs (72%) of consecutive .AOM episodes showed that the isolates were different, and there was little difference between the results of PBP gene mutation and PFGE analysis.
These findings suggest that most nasopharyngeal isolates from children with AOM possess PBP mutations and children with increased numbers of drugresistant bacteria in their nasopharynx during AOM has been or recolonized by different strains during each episode. We therefore emphasize that clinicians should assess the antibiotic susceptibility of nasopharyngeal isolates from children during each episode. PBP gene mutation analysis of S. Pneumoniae is useful not only in providing valuable information on the antibiotic susceptibility of each strain but for assessing changes in causative strains in the sequential episodes of pneumococcal infection.

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