Surgical treatment of otosclerosis using a unique stapes prosthesis without a hook.

BACKGROUND: During stapes surgery, the Teflon wire piston prosthesis is prone to postoperative 'slips' and subsequent necrosis and fracture of the long process of the incus. AIMS/OBJECTIVE: We invented and used a novel cup-shaped apatite prosthesis to reduce the incidence of necrosis of the long process of the incus and analysed the postoperative results. MATERIAL AND METHODS: Thirty-one ears in 25 patients with otosclerosis who underwent stapes surgery with our apatite prosthesis were evaluated. RESULTS: The air conduction improved by 24.0 dB (the average) from pre- to post-operation. Additionally, 84.8% of patients achieved an air-bone gap of ≤10 dB for the 4-frequency measurements (p < .01). CONCLUSIONS: Our findings indicate that our new prosthesis was associated with a good postoperative prognosis in patients with otosclerosis. SIGNIFICANCE: Our unique prosthesis yielded good outcomes for the treatment of otosclerosis even in the short term.

Tetraethylammonium and tetrodotoxin: effects on cochlear potentials.

Tetraethylammonium chloride, which is believed to decrease potassium conductance, and tetrodotoxin, which apparently decreases sodium conductance in nerve fibers, were introduced iontophoretically into the organ of Corti or the scala media of guinea pig cochlea. The former depressed the direct-current endocochlear potential and also the alternating-current cochlear microphonics (the receptor potential of the ear), but tetrodotoxin was ineffective except on the nerve impulses.

Activation of matrix metalloproteinase-2 in head and neck squamous cell carcinoma: studies of clinical samples and in vitro cell lines co-cultured with fibroblasts.

We undertook this present study to investigate the activation of matrix metalloproteinase-2 (MMP-2) in human head and neck squamous cell carcinomas (HNSCC) tissues and cell lines. Gelatinolytic activities of active MMP-2 were significantly higher in carcinoma samples than in normal portions. Furthermore, the activation ratio of proMMP-2 significantly correlated with cervical lymph node metastasis. In vitro studies revealed an HNSCC cell line, HEp-2, to produce neither the pro form nor the active form of MMP-2, but human fibroblasts were found to produce proMMP-2. However, coculture of HEp-2 cells with fibroblasts resulted in the production of not only proMMP-2 but also activeMMP-2 in the culture medium. Northern blot analysis revealed a stronger expression of membrane-type 1 matrix metalloproteinase (MT1-MMP),which is a specific activator of MMP-2, mRNA in HEp-2 cells than in fibroblasts. These results suggest the activation of proMMP-2 as an important event in the process of HNSCC metastasis. They also suggest MMP-2 is secreted in its pro form by stromal fibroblasts surrounding the cancer cells and activated by MT1-MMP localized on the cancer cells.

Granulocyte-macrophage colony-stimulating factor upregulates matrix metalloproteinase-2 (MMP-2) and membrane type-1 MMP (MT1-MMP) in human head and neck cancer cells.

Matrix metalloproteinase-2 (MMP-2) and membrane type 1-MMP (MT1-MMP) play an important role in the invasion and metastasis of head and neck squamous cell carcinoma (HNSCC), but the mechanism of their regulation is not clearly understood. Recently, granulocyte-macrophage colony-stimulating factor (GM-CSF) has been shown to be associated with cancer invasion and metastasis. We hypothesized that GM-CSF may upregulate MMP-2 and/or MT1-MMP expression in HNSCC cells, and may thereby influence their ability to invade and metastasize. We studied the effects of GM-CSF on the production of MMP-2 and MT1-MMP in HNSCC cell lines SAS and HSC-2. Gelatin zymography of conditioned media derived from HNSCC cells revealed a major band of 68 kDa, which was characterized as proMMP-2. GM-CSF stimulated the production of proMMP-2 in both cell lines in a dose-dependent manner. Treatment with 50 ng/ml GM-CSF for 24 h increased the proMMP-2 activity 3.4-fold in SAS cells and 2.3-fold in HSC-2 cells compared with untreated controls. Northern blot analyses demonstrated that GM-CSF led to elevated mRNA levels of MMP-2 and MT1-MMP in both cell lines. The results identify GM-CSF as a regulator of MMP-2 and MT1-MMP expression in certain types of HNSCC, and suggest that GM-CSF may contribute to the invasiveness of HNSCC through the regulation of MMP-2 and MT1-MMP expression.

Clinical significance of expression of membrane type 1 matrix metalloproteinase and matrix metalloproteinase-2 in human head and neck squamous cell carcinoma.

Three different membrane-type matrix metalloproteinases (MT-MMPs) activate in vitro the latent form of matrix metalloproteinase-2 (MMP-2), which is one of the key proteinases in invasion and metastasis of various cancers. We examined the mRNA expression of MT1, 2, and 3-MMPs and MMP-2 in cell lines of head and neck squamous cell carcinoma (HNSCC) and quantitated the relative expression levels in human HNSCC tissues by Northern blotting. The tissue localization of MT1-MMP and MMP-2 was determined by immunohistochemistry and in situ hybridization. Their implications in clinicopathologic factors were statistically evaluated. All cell lines examined consistently expressed MT1-MMP and MMP-2, but not MT2, 3-MMP. In the clinical specimens, there was a significant correlation in coexpression of messenger of RNA (P = .0005) and colocalization by immunohistochemistry (P < .0001) for MT1-MMP and MMP-2. Relative mRNA expression levels of MT1-MMP and MMP-2 in the carcinoma tissues were significantly higher than those of the control tissues (P = .0045 and P = .0122, respectively). Both mRNA expression level and immunopositivity of MT1-MMP significantly correlated with lymph node metastasis (P = .0081 and P = .0193, respectively), which was confirmed by multivariate logistic regression analysis. Immunoreaction of MT1-MMP and its mRNA expression were observed in both carcinoma cells and stromal cells. The localization of MMP-2 closely corresponded to that of MT1-MMP. These observations suggest that MT1-MMP possesses a role as a determinant of lymph node metastasis in HNSCC, and that concurrent expression of MT1-MMP and MMP-2 are involved in progression of HNSCC.

A clinical study on T1 glottic cancer treated by laser technique.

It is commonly accepted that radiotherapy is a first choice for treatment of T1 glottic cancer. However, side effects caused by irradiation are sometimes troublesome to a patient and to a physician. Among side effects, oncogenic problem and late radiation change are most undesirable and may become fatal. Hence, we avoid radiation therapy especially for younger aged patients. We prefer surgical therapy to radiotherapy for such a case. In our clinic, laser therapy has been employed. A laser beam is introduced through an operation microscope and a lesion can be microscopically vaporized. In this study, a survey of 40 patients with T1 glottic cancer submitted to laser surgery was reviewed. From those patients 25 were T1a and 15 were T1b. From our experience, laser vaporization is recommendable for T1 glottic cancer in younger aged patients. However, in order to obtain cure rate comparable to radiation therapy, the indication must be correctly designated.

Expression of matrix metalloproteinase-1 mRNA related to eosinophilia and interleukin-5 gene expression in head and neck tumour tissue.

In situ hybridization (ISH) of the expression of matrix metalloproteinase-1 (MMP-1) in areas of local invasion of head and neck tumours was performed. Expression of MMP-1 mRNA was found in stromal inflammatory cells adjacent to the tumour nests, apparently in eosinophils. MMP-1 mRNA expression was seen only in cases with moderate or greater stromal eosinophilia. MMP-1 mRNA was detected in benign papilloma and verrucous carcinoma. In squamous cell carcinomas, expression of the gene was detected only in well-differentiated cases. Expression of MMP-1 mRNA was not related to the grade of malignancy, and appeared in stromal eosinophils, suggesting to us that it is involved in a remodelling process in the reaction of the host to tumour invasion. ISH examination of the expression of interleukin-5 (IL-5), the activating factor for eosinophils, was also performed. In the tumour, its expression was consistent with the location of eosinophils, as with MMP-1 mRNA, suggesting an autocrine mechanism.

The glutamate receptor agonist, AMPA, induces acetylcholine release in guinea pig cochlea; a microdialysis study.

Acetylcholine (Ach) has been considered a major neurotransmitter in the inner ear efferent nerve endings. A bioassay analysis has shown that the electrical stimulation of the crossed olivocochlear bundle increased the Ach-like activity in the perilymph. Applying in vivo microdialysis techniques and high-performance liquid chromatography to the perilymph, the change of Ach level was thus measured before and after alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA), a glutamate receptor agonist, was added to the perfusate. Ach was only detectable when the perfusate contained an acetylcholinesterase inhibitor. The level of Ach increased 2-3-fold immediately after AMPA was administered. Our data suggest that the afferent stimulation, such as the administration of AMPA, may therefore induce the release of Ach from the efferent nerve endings.

A modified extended middle cranial fossa approach for acoustic nerve tumors. Results of 125 operations.

During the past 10 years, 125 operations for acoustic nerve tumors were performed on 114 patients at the authors' institution using a modified extended middle cranial fossa approach. This approach is based on a combination of King and Morrison's translabyrinthine-transtentorial approach and on the extended approach through the middle cranial fossa described by Bochenek and Kukwa. There were two hospital deaths (operative mortality 1.6%). In 102 operations on the initial tumor, total removal was performed in 89 cases (87%), and in 71 (80%) of these the facial nerve was anatomically preserved. Intracranial end-to-end anastomosis was performed on five of the 18 sacrificed facial nerves; a facial-hypoglossal anastomosis was carried out in the remaining 13 patients and in five (7%) of the 71 patients whose anatomically preserved facial nerve functioned poorly. In seven (39%) of the 18 patients in whom an attempt to preserve hearing was made, postoperative hearing was saved. In 23 operations on 17 patients for recurrent tumors, most of which had previously been removed subtotally via the suboccipital approach, total removal was accomplished in 13 (57% of the 23 reoperations and 76% of the 17 patients). At reoperation, the facial nerve was preserved in six (55%) of the 11 patients in whom the facial nerve had not been sacrificed. Postoperative leakage of cerebrospinal fluid occurred in 11 cases (8.8%), with rhinorrhea in 10 cases and otorrhea in one. Five of the fistulas were corrected by surgery and the rest healed spontaneously. Other complications were not significant.

Ultrastructure of astrocytes in the transitional region of the human eighth cranial nerve.

The nerve root segment where the transition from central to peripheral nervous tissue occurs is referred to as the transitional region (TR). Part of the TR is a continuation of the subpial glial limiting membrane (SGLM) which covers the surface of the brain. To assess the physiological and pathophysiological roles of astrocytes in the TR of the human eighth cranial nerve, electron microscopy was performed on surgically resected specimens of the eight cranial nerve root obtained from patients with cerebellopontine angle tumors. The astrocytic glial dome was sharply bounded by a basement membrane and was mainly composed of the bodies and processes of fibrous astrocytes. Desmosomes and gap junctions were found between these astrocytic processes. Half-desmosomes were found on the edge of the astrocytic glial dome and at the luminal surface of the perivascular glial limiting membrane. These ultrastructural features indicate that the astrocytes of the TR might have some motility capacity that allows adjustment to changes in the pressure exerted by the vessels, the peripheral nervous tissue, and the cerebrospinal fluid. In addition, it is also suggested that lack of structures linking the central and peripheral portions of the nerve and the abrupt change of nerve composition at the TR might predispose this area to injury by tractional forces or pathologic conditions such as tumor or arterial compression.

The vasculature of the peripheral portion of the human eighth cranial nerve.

The vasculature of the peripheral portion of the human eighth cranial nerve (VIIIN) was investigated by light and transmission electron microscopy. Arterioles and venules running longitudinally around the VIIIN formed the extrinsic vascular system. The anatomical relationship between these extrinsic vessels and the VIIIN sheath was similar to that between blood vessels on the surface of the brain and the pia mater. In the endoneurium, postcapillary venules and large capillaries were sparsely distributed and longitudinally arranged, and these microvessels formed the intrinsic microvascular system, which was supported by the extrinsic vascular system via anastomosing vessels. The ultrastructural features of the internal auditory artery and its main branches were the same as those of other intracranial arteries. Ultrastructural study also revealed myo-endothelial junctions in anastomosing arterioles, and endothelio-pericytic junctions in extrinsic and anastomosing venules. Microvascular endothelial cells were connected by tight junctions in both the vestibular ganglion and the rest of the VIIIN. These features of the vasculature were considered to be effective for maintenance of the endoneurial fluid and regulation of the circulation in the peripheral portion of the human VIIIN.

Effects of changes in stimulus level on phases of distortion product otoacoustic emissions.

Effect of changes in stimulus levels of both lower (f(1)) and higher (f(2)) stimulus tones on phases of 2f(1)-f(2) component of the distortion product otoacoustic emission (DPOAE) was examined in five normal hearing adults. The f(2) was fixed at 4004 Hz in all of the measurements, and the stimulus frequency ratio (f(2)/f(1)) was varied from 1.15 to 1.3. Change of the level of lower stimulus tone (L(1)) and the level of higher stimulus tone (L(2)) showed different effects on the DPOAE phases. The phase lags increased with increasing L(1), when f(2)/f(1) was above 1.22, whereas the phase gains increased with increasing L(1), when f(2)/f(1) was below 1.22. On the other hand, the difference in L(2) minimally affected DPOAE phase at most f(1)s. The previous studies about basilar membrane vibration revealed that phase lags increase with increasing stimulus level, when the stimulus frequency is below the best frequency, while phase gains increase with increasing stimulus level, when the stimulus frequency is above the best frequency, and the effect of phase change in stimulus level diminished, when the stimulus frequency was far above the best frequency. Based on the comparison between the results of the present study and the previous findings of others concerning basilar membrane vibration, the DPOAE generation site is assumed to be located at apical of the peak of the f(2) traveling wave.

Human leukocyte antigen in childhood unilateral deafness.

Human leukocyte antigen frequencies were examined in 40 Japanese patients with severe unilateral sensorineural hearing loss found in childhood. Human leukocyte antigen-Bw54 was significantly increased in frequency. No statistically significant deviation in the Bw54 frequency was observed among several possible subgroups studied. Although this group of patients may have various causes, and underlying mechanism is still unclear, this preliminary study suggests that childhood unilateral deafness may be associated with a genetically determined factor(s).

Role of CD44 variant exon 6 in invasion of head and neck squamous cell carcinoma.

OBJECTIVES: To determine the correlation between the expression of CD44 variant exon 6 (v6) and the clinicopathological features of head and neck squamous cell carcinomas (HNSCCs), and to study the role of CD44v6 in cell invasion using a human HNSCC cell line (HSC-2). DESIGN: The expression of CD44v6 was evaluated using immunohistochemical analysis in paraffin-embedded tissue specimens from 89 primary lesions. The concentration of CD44v6 protein in 37 cryopreserved tumor specimens was evaluated using the enzyme-linked immunosorbent assay. The HSC-2 cells were treated with 2F10, a monoclonal antibody against CD44v6. The effects of 2F10 on HSC-2 cell proliferation, migration, and invasion potential were evaluated. RESULTS: The down-regulation of CD44v6 expression or the concentration of cancer tissue significantly correlated with a lower degree of pathohistological differentiation and a higher rate of cervical metastasis. The invasion of HSC-2 cells into type I collagen gel and the expression of CD44v6 were decreased in invading cells released from the upper layer. Furthermore, the treatment of HSC-2 cells with 2F10 significantly enhanced cell invasion. However, 2F10 did not affect either the proliferation or migration properties of HSC-2 cells. CONCLUSIONS: The down-regulation of CD44v6 expression may be useful as a biological marker for the degree of malignancy in HNSCCs. We assume that the loss or dysfunction of CD44v6 is involved in the acquisition of invasion ability in HSC-2 cells. In addition, the potential existence of a CD44v6-mediated signal transduction pathway may play a role in inhibiting the invasion in HNSCCs.

Analysis of vocal fold vibration by x-ray stroboscopy with multiple markers.

OBJECTIVE: To derive a more precise description of vocal fold vibration, experimental phonation of excised canine larynxes was studied. STUDY DESIGN AND SETTING: Multiple X-ray-positive markers were inserted, and their vibratory movement was observed with x-ray stroboscopy with change of pitch and intensity. A histologic study was also carried out. RESULT: Regular waves were observed just above the lowest point of the lamina propria of the mucous membrane, which shifted upward at high pitch, but downward in high intensity. CONCLUSIONS: The starting point of the mucosal wave was confirmed on the lower surface of the vocal fold, histologically just above the lowest point of the lamina propria of the mucous membrane and shifted upward at high pitch, but downward in high intensity. SIGNIFICANCE: This is the first study investigating the starting point of mucosal wave in vocal fold vibration in a frontal plane using x-ray stroboscopy, providing the evidence for the body-cover theory.

Psychological aspects of psychogenic deafness in children.

Twenty-nine children with psychogenic deafness were investigated from audiological and psychological aspects. ABR and Békésy audiometry were useful for diagnosing psychogenic deafness. The elapsed time from the start of treatment to audiometric recovery was significantly shorter in patients receiving psychological treatment, indicating that treatment by a team of otologists and counselors was able to hasten recovery in children with psychogenic deafness. The pattern of hearing recovery in the treated group was classified into 3 types and in the control group into 4 types. Counseling seemed to have a positive effect on patients with fluctuating improvement. In the patients in the treated group, the elapsed time to audiometric recovery from the beginning of psychological treatment was 7.5 months; however, in the control group recovery it took 17.1 months. Psychological treatment revealed that the clinical course of psychogenic deafness in children seemed to have some relation to the patient's personality and psychological stresses.

Gliosis of the eighth nerve transitional region in patients with cerebellopontine angle schwannoma.

The central-peripheral transitional region (TR) of the eighth nerve root was obtained from 8 patients with cerebellopontine angle schwannoma and investigated by light microscopy, electron microscopy, and immunohistochemistry. As a control, the TRs of 6 autopsy patients without any otologic disease were studied. Astrocytic proliferation at the TR was more prominent in the schwannoma patients than in the normal controls. Mild gliosis of the mantle zone of the TR was found in 5 schwannoma patients and moderate gliosis was noted in 3. The distribution of capillaries at the TR differed between the schwannoma patients and the normal controls. In the schwannoma patients, capillaries were rarely found in the mantle zone of the TR but were densely clustered at the glial fringe zone, especially near its border with the peripheral nervous tissue. Stasis of the capillaries in the glial fringe zone was frequently noted. These histological findings may indicate the occurrence of gliosis in response to eighth nerve degeneration. We suggest that there is increased susceptibility of the eighth nerve to injury at the TR in patients with schwannoma.

Quality of life of vestibular schwannoma patients after surgery.

The quality of life of vestibular schwannoma (VS) patients after surgery was investigated. The subjects consisted of 236 unilateral VS patients who underwent tumor removal between 1990 and 1997. A questionnaire was sent to all patients regarding their hearing, tinnitus, dizziness and the changes in their daily life after surgery; 176 out of 204 patients (86%) who received the questionnaire completed and returned it. The answers were compared with recent data reported in other clinical studies. Ninety percent of the patients with postoperative class A hearing were satisfied with their hearing. However, only 30% of patients with postoperative class B hearing were satisfied. Tinnitus worsened after surgery more often in patients who underwent a labyrinthectomy than in those who did not. Dizziness improved after surgery in the majority of VS patients. However, 30% of patients had difficulty driving a car and 50% of patients could not enjoy activities such as playing sport after surgery.

Angiogenesis from the eighth cranial nerve to vestibular schwannomas.

Vascularization between vestibular schwannomas and the adjacent eighth cranial nerve was examined in order to elucidate the angiogenic effect of these tumours. Specimens from 12 patients were examined by light microscopy and immunohistochemistry (series 1), while specimens from another 17 patients were examined by light and transmission electron microscopy (series 2). Slight to marked angiogenesis was found in 5 patients from series 1 and 7 patients from series 2. Ultrastructural examination indicated that these blood vessels were more fragile than those in the normal eighth cranial nerve. These findings suggested that sudden hearing loss in vestibular schwannoma patients may be related to the disruption of such blood vessels. In addition, surgical injury to these blood vessels may cause postoperative hearing loss despite preservation of the cochlear nerve.

The limitations of hearing preservation in acoustic neuroma surgery: histological study of the interface between the eighth cranial nerve and the tumor.

The interface between the eighth cranial nerve and acoustic neuroma was investigated by light microscopy and immunohistochemistry in paraffin sections in 13 patients, and in Epon sections in 19 patients. The cochlear nerve was severely invaded by tumor cells in two of six specimens examined, moderately invaded in two specimens, and not invaded in two specimens. Gliosis was frequently found within the cochlear and vestibular nerve. Hemangioma-like tissue was occasionally found attached to the cochlear and vestibular nerve adjacent to the tumor. These findings were considered to be related to difficulty in hearing preservation in some patients although acoustic neuroma surgery was successful.