Spontaneous inversion of nystagmus without a positional change in the horizontal canal variant of benign paroxysmal positional vertigo.

OBJECTIVE: We investigated the neuro-otological findings, including nystagmus, and the clinical course of patients with the horizontal canal variant of benign paroxysmal positional vertigo (HC-BPPV), who showed spontaneous inversion of nystagmus without a positional change. Furthermore, we speculated on the possible mechanism of spontaneous inversion of nystagmus without a positional change. PATIENTS AND METHODS: The characteristics of spontaneous inversion of positional nystagmus without a positional change were analyzed in 7 patients with HC-BPPV. RESULTS: All patients were diagnosed as having HC-BPPV. During the positional test, the spontaneous inversion of nystagmus was observed in the same head position in all patients. Spontaneous inversion was observed on both sides in 5 patients, and only on 1 side in 2 patients. All patients presented with geotropic nystagmus in the first phase, and ageotropic nystagmus in the second phase. CONCLUSIONS: The coexistence of cupulolithiasis and canalolithiasis appears to be a possible mechanism of the spontaneous inversion of positional nystagmus.

Ocular vestibular evoked myogenic potentials induced by bone-conducted vibration in patients with unilateral inner ear disease.

CONCLUSION: Patients with vestibular neuritis (VN) with complete canal paresis (CP) showed a higher rate of abnormal ocular vestibular evoked myogenic potential (oVEMP) than those with partial CP. From these results, it is speculated that the superior vestibular nerve function mainly affects oVEMP. Significant correlation was found between the grades of the hearing outcome and oVEMP in sudden sensorineural hearing loss (SSHL). OBJECTIVE: We attempted to correlate the results of oVEMP with the results of cervical VEMP (cVEMP), results of subjective visual vertical (SVV), and clinical course in patients with various vestibular disorders. METHODS: Twenty-two patients with VN, 65 with SSHL, and 22 with Meniere's disease (MD), were enrolled in this study. We compared the results of oVEMP with those of cVEMP, SVV, and the caloric test. Furthermore, the oVEMP results were compared with the initial hearing threshold, presence of vertigo, and hearing recovery in the patients with SSHL. RESULTS: The patients with VN with complete CP showed a higher rate of abnormal oVEMP than those with partial CP. In the patients with SSHL, the hearing recovery rate was lower in the patients with abnormal oVEMP than in those with normal oVEMP.

Intermittent positional downbeat nystagmus of cervical origin.

Intermittent positional down beat nystagmus (p-DBN) is rare. We describe an unusual case of intermittent p-DBN which was induced by rotation, anteflexion, and lateral flexion of the neck. A 59-year-old man complained of loss of consciousness and lightheadedness. Positional testing revealed the p-DBN. The evoked p-DBN had latency and the patient had a feeling of passing out while the p-DBN was present. There were no abnormal findings in the vestibular functional examinations. Findings of the MRI were negative. MRA revealed no stenosis of the vertebral artery bilaterally, but there was an anatomical difference. The p-DBN characteristics were documented by electronystagmography during the positional test. The p-DBN lasted intermittently while maintaining the provoking position. It was found that p-DBN occurred with not only the rotation of the neck, but also in the anteflexion and lateral flexion of the neck. There was no stenosis of the vertebral artery (VA) on angiography, but we speculated that the cause of the p-DBN was the VA occlusion due to rotation, anteflexion, and lateral flexion of the neck.

Subjective visual vertical perception in patients with vestibular neuritis and sudden sensorineural hearing loss.

OBJECTIVE: To determine the subjective visual vertical (SVV) perception in patients with vestibular neuritis (VN) and sudden sensorineural hearing loss (SSHL) using the SVV test and other neuro-otological examinations, namely, the vestibular evoked myogenic potential (VEMP) and caloric tests, and to clarify which vestibular nerve function is associated with an SVV shift. PATIENTS AND METHODS: We performed the SVV test in 36 VN patients and 80 SSHL patients. Thereafter, we investigated directional changes in the SVV in the VN and SSHL patients, and compared the results of the SVV test with those of the VEMP and caloric tests. RESULTS: Abnormal SVV (> 2° was found at a rate of 69.4% in the VN patients and 26.3% in the SSHL patients. In all except 1 VN patient, the SVV tilted to the lesion side. The rate of abnormal SVV was significantly higher in patients with complete canal paresis (CP) than in patients with partial CP. There was no significant relationship between the rates of abnormal SVV and VEMP. In the SSHL patients, neither the SVV nor the VEMP affected the hearing outcome and patients with abnormal VEMP tended to show abnormal SVV. CONCLUSION: VN patients showed a higher rate of abnormal SVV than SSHL patients. From the results, it is speculated that the superior vestibular nerve function mainly affects the SVV tilt, although the inferior vestibular nerve function may also have an effect.

Changes in the cupula after disruption of the membranous labyrinth.

CONCLUSION: Various changes were observed in the cupula, including shrinkage and enlarged volume, following the disruption of the membranous labyrinth. Cupular change after membranous labyrinth disruption may be a pathology of vestibular disorders. OBJECTIVES: To observe the morphological changes of the cupula after disruption of the membranous labyrinth and to compare the cupular changes with changes in the compound action potential (CAP) of the ampullary nerve. METHODS: A labyrinthine injury model was created by puncturing the membranous labyrinth of bullfrogs. The cupula was observed from 3 to 17 days after the membrane puncture. The CAP in response to mechanical endolymphatic flow was recorded from the ampullary nerve. The correlation between cupular change and CAP positivity was evaluated using the authors' scale. RESULTS: Various kinds of cupular changes including shrinkage were observed. Cupular change was more severe after a longer survival period. Large or elongated volume of the cupula was also observed, which was not observed in our previous study using gentamicin. The CAP could be recorded even when the cupular change was severe.

Blockage of longitudinal flow in Meniere's disease: A human temporal bone study.

CONCLUSION: Blockage of the endolymphatic duct is a significant finding in Meniere's disease. The position of the utriculo-endolymphatic valve (UEV) and blockage of the ductus reuniens in the temporal bones were not found to be directly indicative of Meniere's disease. OBJECTIVE: Comparison of blockage of the longitudinal flow of endolymph between ears affected by Meniere's disease and normal ears. METHODS: We examined 21 temporal bones from 13 subjects who had Meniere's disease and 21 normal temporal bones from 12 controls. RESULTS: The endolymphatic duct was blocked in five (23%) ears affected by Meniere's disease (p = 0.016). The utricular duct was blocked in 16 (76%) ears affected by Meniere's disease and 11 (52%) normal ears (p = 0.112). The saccular duct was blocked in 6 (28%) of ears affected by Meniere's disease and 16 (76%) normal ears (p = 0.001). The ductus reuniens was blocked in 10 (47%) ears affected by Meniere's disease and 10 (47%) normal ears (p = 1.000).

Round window membrane in Ménière's disease: a human temporal bone study.

OBJECTIVES: To disclose the histopathologic findings of the thickness of the round window membrane and the presence of false round window membrane in Ménière's disease. METHODS: Twelve temporal bones from 6 patients with bilateral Ménière's disease, 44 temporal bones from 23 patients with unilateral Ménière's disease, and 102 age-matched normal temporal bones from 56 individuals were histopathologically examined. The thickness of the round window membrane was calculated from 3 different places. In addition, the presence of false round window membrane was investigated in temporal bones with Ménière's disease and compared to the normal temporal bones. RESULTS: A significant difference in the mean thickness of the round window membrane was observed in temporal bones with Ménière's disease compared with normal temporal bones. There was no significant difference in the thickness of the round window membrane between the diseased side and contralateral side in patients with unilateral Ménière's disease. A false round membrane was observed in 9 (25.7%) of 35 Ménière's disease cases and in 5 (4.9%) of 102 normal temporal bones. CONCLUSION: The thickened nature of the round window membrane and the frequent presence of false round window membrane in patients with Ménière's disease may impede the intratympanic injection treatments. The thickened middle layer of the round window membrane may be related to perilymphatic pressure changes observed in patients with Ménière's disease.

Auditory-pupillary responses in deaf subjects.

Pupillary dilation in response to sound stimuli is well established and is generally considered to represent a startle reflex to sound. We believe that the auditory-pupillary response represents not only a simple startle reflex to sound stimuli but also represents a reaction to stimulation of other sense organs, such as otolith organs. Eight young healthy volunteers without a history of hearing and equilibrium problems and 12 subjects with bilateral deafness participated in this study. Computer pupillography was used to analyze the auditory-pupillary responses of both eyes in all subjects. We found that auditory-pupillary responses occurred even in subjects with bilateral deafness and that this response was comparable to those of normal subjects. We propose that the auditory-pupillary response also relates to vestibular function. Thus, assessing the auditory-pupillary response may be useful for evaluating the vestibulo-autonomic response in patients with peripheral disequilibrium.

Effect of cupula shrinkage on the semicircular canal activity.

CONCLUSION: With half-sized cupula, the semicircular canal nerve potentials decreased under slow stimulus, thus potentially leading to reduced caloric response. This also suggests that shrunken cupula may cause dizziness because of its hypermobility. OBJECTIVES: To examine the physiological effect of half-sized cupula on the semicircular canal nerve potential. METHODS: The isolated cupula of the bullfrog was sectioned in half with fine scissors and was replaced on the crista. Mechanical endolymphatic flow and slow and fast stimuli were delivered and the evoked action potentials were recorded. RESULTS: The cupula was successfully sectioned in half and was replaced on the crista. With the half-sized cupula, the action potentials became smaller under slow stimulus than under fast stimulus.

Model experiments of otoconia stability after canalith repositioning procedure of BPPV.

CONCLUSION: Postural restrictions are probably not necessary after the canalith repositioning procedure (CRP). OBJECTIVES: Epley reported the effect of CRP for benign paroxysmal positional vertigo (BPPV). After CRP, patients are often requested to restrict postural change. However, some studies suggested that CRP may work without postural restrictions. The present study aimed to determine the necessity of post-maneuver postural restriction using the frog labyrinth model. METHODS: The otoconial mass from the sacculus was placed on the utricular macular otoconia, mimicking a condition after CRP. The stability of the otoconial mass was observed by tilting the preparation, immediately, 3 min, and 5 min after it was placed on the macular otoconia. The utricular macula was maintained in the vertical plane for 10 s, during which period the behavior of the otoconial mass was observed. In experiment 1 the utricular macula was intact, in experiment 2 otoconia were partially removed, and in experiment 3 they were totally removed from the macula. RESULTS: In experiments 1 and 2, in all preparations the otoconial mass became stabilized after 3 min. Even in experiment 3, in most preparations the otoconial mass became stabilized after 5 min.

Subjective visual vertical in patients with ear surgery.

CONCLUSION: Dysequilibrium is one of the most important side effects of ear surgery. The subjective visual vertical can be used as a good indicator for the evaluation of otolithic function in patients with ear surgery. OBJECTIVE: To investigate the influence of various types of ear surgery on the otolithic organs. METHODS: Seventy-one patients underwent ear surgery. Subjective visual vertical (SVV) test was performed before and after ear surgery. We investigated the directional changes of SVV before and after the ear surgery. RESULTS: The postoperative SVV of two patients who underwent translabyrinthine removal of vestibular schwannoma shifted toward the operated side, but following other surgical procedures the SVV tended to shift toward the healthy side.

Morphological change of the cupula due to an ototoxic agent: a comparison with semicircular canal pathology.

CONCLUSION: The cupula shows various degrees of changes after gentamicin (GM) injection into the inner ear, with or without damage of the sensory cells. This cupula change may be a part of the etiology of peripheral vertigo, and is also potentially one of the mechanisms of reduced caloric response. OBJECTIVES: To observe the morphological changes of the cupula after injecting GM in the frog inner ear and to compare the changes of the cupula with those of the ampullary sensory cells. METHODS: We injected 300 microg (7.5 microl) of GM into the inner ear of 30 bullfrogs (Rana catesbeiana) using a microsyringe under ether anesthesia. The same amount of saline was injected into the other ear as control. The cupulae were observed at 3, 7, and 14 days after GM injection by stereoscopic microscope. The ampullae were fixed, and the sensory cells were assessed using a scanning electron microscope (SEM). The correlation between the changes in the cupula and sensory cells was evaluated using our own scale. RESULTS: In over half of the cupulae in the 7- and 14-day groups, cupula changes such as shrinkage were observed. In about 50% of the total cases, the degree of cupula and sensory cell change correlated in the two groups. In the 14-day group, these changes were more marked. However, there were cases in which the changes of the cupula and sensory cells did not correlate, indicating that the cupula alone can sustain changes without sensory cell damage.

Bilateral progressive hearing loss and vestibular dysfunction with inner ear antibodies.

Autoimmune inner ear disease (AIED) is a clinical syndrome of uncertain etiology. We present the neuro-otological findings of 2 cases of bilateral hearing loss, dizziness and the antibody profiles of the inner ears. Case 1 had bilateral progressive hearing loss, vestibular dysfunction and abnormal eye movement as the disease progressed. She had inner ear antibodies against 42 and 58kDa protein antigency on Western blot immune assay, and responded to glycocorticosteroid but not to immunosuppressant treatment. Intratympanic steroid injection temporally eliminated her symptoms. However, she developed idiopathic Cushing's syndrome and underwent labyrinthectomy. Case 2 became deaf as a teenager and experienced dizziness 10 years after becoming deaf. He reacted strongly to 68kDa protein and was a good responder to immunosuppressant with steroid. As we still lack a definitive diagnostic test for AIED, careful observation of the clinical course is critical for differential diagnosis regarding the bilateral progressive hearing loss.

Fluctuating mixed-type hearing loss associated with synovitis-acne-pustulosis-hyperostosis-osteomyelitis (SAPHO) syndrome.

Synovitis, acne, palmoplantar pustulosis (PPP), hyperostosis, and osteitis (SAPHO) are the characteristic features of SAPHO syndrome. A 53-year-old woman had been treated for PPP for 2 years. She complained of hearing loss in the right ear, and otitis externa was diagnosed. The pure-tone audiogram (PTA) indicated mild hearing loss in the right ear, and her hearing continued to deteriorate despite recovery from inflammation. Her tympanogram was of the As-type, and acoustic reflex was absent in the right ear. A computed tomography (CT) scan revealed bilateral normal ossicles and cochleas. Bone scintigraphy revealed tracer uptake in the bilateral sternoclavicular joints, glenohumeral joints, and the capital humerus. She was hospitalized for arthralgia, and the pain was controlled with steroid therapy. Her right hearing deteriorated soon after the tapering of the steroid; her hearing recovered after cyclosporine therapy was initiated. The first tonsil provocation test showed increased blood cells in the urine, and the second test showed exacerbation of pustulosis. Despite immunosuppressant therapy, the arthritis attacks and hearing loss persisted; therefore, tonsillectomy was performed, which improved PPP. However, her hearing remained unchanged after the operation. We considered that irreversible changes might have already developed in the ossicular joints, and ossicular reconstruction was performed. Thereafter, her hearing and earache improved.

[Clinical photodynamic diagnosis and therapy efficiency in oropharyngeal cancer].

OBJECTIVES: We studied photodynamic diagnosis (PDD) and therapy (PDT) applicability using NPe6 in with oropharyngeal cancer patients. METHODS: Of 11 subjects diagnosed with oropharyngeal cancer undergoing PDT and PDD using NPe6, 6 were stage T1 and 5 stage T2. None had nodal or distant metastases. Four hours before PDD, NPe6 (40 mg/mD) was injected intravenously. Under general anesthesia, tumor fluorescence observed by laser irradiation, and marked was followed by PDT and photobleaching was confirmed. Tissue collected from tumor centers confirming NPe6 was then compared to normal tissue specimens and the relationship between NPe6 concentration and treatment effectiveness studied. RESULTS: Tumor marking enabled us ensure a safety margin because the fluorescence scope exceeded tumor scope to the naked eye. Photobleaching was confirmed in all subjects. NPe6 tumor tissue concentration was 1.57-6.84 microg/g, with a ratio of 2.32-5.69 compared to normal tissue. Treatment achieved complete recovery (CR) in all subjects and shortened hospitalization over other treatment such as radiation. CONCLUSION: PDD using NPe6 clearly benefited oropharyngeal cancer patients, and made PDT more accurate. NPe6 accumulated more than twice the level in tumor tissue than in normal tissue.

Positional and positioning down-beating nystagmus without central nervous system findings.

We report the clinical features of 4 cases with positional or positioning down-beating nystagmus in a head-hanging or supine position without any obvious central nervous system disorder. The 4 cases had some findings in common. There were no abnormal findings on neurological tests or brain MRI. They did not have gaze nystagmus. Their nystagmus was observed only in a supine or head-hanging position and it was never observed upon returning to a sitting position and never reversed. The nystagmus had no or little torsional component, had latency and tended to decrease with time. The positional DBN (p-DBN) is known to be indicative of a central nervous system disorder. Recently there were some reports that canalithiasis of the anterior semicircular canal (ASC) causes p-DBN and that patients who have p-DBN without obvious CNS dysfunction are dealt with anterior semicircular canal (ASC) benign paroxysmal positional vertigo (BPPV). There are some doubts as to the validity of making a diagnosis of ASC-BPPV in a case of p-DBN without CNS findings. It is hard to determine the cause of p-DBN in these cases.

Therapeutic effects of a new photosensitizer for photodynamic therapy of early head and neck cancer in relation to tissue concentration.

OBJECTIVE: Talaporfin sodium (Laserphyrin, Meiji Seika, Tokyo, Japan) is a second-generation photosensitizer developed in Japan. It is characterized by both mild and short-term skin photosensitivity. The objective of this study was to evaluate the efficacy and the pharmacokinetic characteristics in tumor tissues in patients with head and neck cancer. METHODS: (1) Four hours after administration intravenous injection of talaporfin sodium (40 mg/m(2)), 100mg tissue specimens were taken from the central part of the tumor. The samples were analyzed by reverse phase liquid chromatography and concentrations were measured. (2) Four hours after intravenous injection of talaporfin sodium (40 mg/m(2)), we gave 60-150 J/cm(2) of 664 nm laser irradiation with a diode laser (PD laser, Panasonic, Japan). Biopsies were performed at 4 weeks and at 3 months after treatment and periodically thereafter to confirm the treatment efficacy of photodynamic therapy (PDT). RESULTS: Of the 14 patients who grope informed consent, more than 1 microg/g of talaporfin sodium was found in the tumor tissues in 13. Moreover, in 9 patients, tumor-to-normal-tissue ratios ranged from 2.32:1 to 5.69:1, which indicates that more than double the amount of talaporfin sodium was maintained within the tumor than in normal tissues. We have enrolled 22 patients with head and neck cancer with no clinically recognizable metastases after obtaining written informed consent to participate in this study. PDT using talaporfin sodium exhibited the equivalent efficacy to that of conventional PDT using hematoporphyrin derivative (HpD). CONCLUSIONS: The results using a combination of talaporfin sodium and PD laser achieved a primary treatment outcome equivalent to that of conventional PDT. This method has also proven to be advantageous because of the reduced incidence of side effects such as photosensitivity and local edema.

A phase I-II study of bi-weekly docetaxel combined with radiation therapy for patients with cancer of the larynx/hypopharynx.

BACKGROUND: We performed a phase I/II study of bi-weekly docetaxel in combination with concurrent radiotherapy to enhance the cytotoxic effect and radiosensitization and improve the rate of laryngeal preservation. METHODS: Patients with T2N0-1M0, T3N0M0 hypopharyngeal cancer or T2N0-1M0, T3N0-1M0 larynx cancer were enrolled. Docetaxel was administered bi-weekly (days 1, 15, 29) from the first day of radiotherapy, while 2 Gy/day of radiation was given on 5 days weekly from day 1, reaching a total of 60 Gy in 30 fractions. RESULTS: 12 patients took part in the phase I study. The maximum tolerated dose (MTD) was 40 mg/m2 and the recommended dose (RD) was determined as 35 mg/m2. The phase II study was conducted with docetaxel at 35 mg/m2 for 25 patients. Treatment was completed without interruption in 24 patients, with a protocol implementation rate of 96%. The complete response rate was 100% in laryngeal cancer, and 80% in hypopharyngeal cancer, and total (including partial response) overall response rate was 100%. The laryngeal preservation rate was 96%, and the overall local control rate was 92%. All patients have been alive for at least 3 years without any recurrence. CONCLUSIONS: The chemoradiation therapy using bi-weekly docetaxel is an extremely effective treatment for cancer of the larynx/hypopharynx, provided that it is used for the specified stage of cancer.

Differentiation and apoptosis in human malignant melanoma G-361 cells induced by 2-aminophenoxazine-3-one.

Inhibitory effects of 2-amino-4,4alpha-dihydro-4alpha,7-dimethyl-3H-phenoxazine-3-one (Phx-1), 2-amino-4,4alpha-dihydro-4alpha,7-dimethyl-3H-phenoxazine-3-one (Phx-2) and 2-aminophenoxazine-3-one (Phx-3), which were produced by the reaction of o-aminophenol and its derivatives with bovine hemoglobin, on the proliferation of human malignant melanoma G-361 cells were studied under various conditions. Phx-1 and Phx-3 showed anti-proliferative effects on human malignant melanoma G-361 cells, however Phx-2 did not. Phx-3, which exerted the strongest anti-proliferative effects, inhibited the proliferation of human malignant melanoma G-361 cells during 24 h incubation at concentrations of >or=10 microM. Apoptosis and G1 arrest in the cells, which were detected by DNA laddering on electrophoresis and flow cytometry, respectively, were observed when the melanoma G-361 cells were treated with Phx-3 at 37 degrees C for 24 h. Concomitantly, the increased melanin formation in G-361 cells was indicated by biochemical and morphological detection of melanin within 24 h exposure to Phx-3. The present results suggest that Phx-3 exclusively demonstrates anti-tumor activity against human malignant melanoma G-361 cells by inducing cell cycle accumulation at G1, differentiation and apoptosis.

Phenoxazine compounds produced by the reactions with bovine hemoglobin show antimicrobial activity against non-tuberculosis mycobacteria.

We studied the anti-microbial effects of phenoxazines produced by the reaction of o-aminophenol or its derivatives with bovine hemoglobin, on seven species of mycobacteria such as Mycobacterium tuberculosis, Mycobacterium marinum, Mycobacterium intracellulare, Mycobacterium scrofulaceum, Mycobacterium fortuitum, Mycobacterium kansasii and Mycobacterium smegmatis and some bacteria such as Escherichia coli, Pseudomonas aeruginosa, Salmonella enterica serovar Typhimurium, Staphylococcus aureus, Listeria monocytogeneses. These phenoxazines, including 2-amino-4, 4alpha-dihydro-4alpha, 7-dimethyl-3H-phenoxzine-3-one (Phx-1), 3-amino-1, 4alpha-dihydro-4alpha, 8-dimethyl-2H-phenoxazine-2-one (Phx-2), and 2-aminophenoxazine-3-one (Phx-3), prevented the proliferation of four non-tuberculosis mycobacteria including M. scrofulaceum, M. kansasii, M. marinum, and M. intracellulare dose-dependently, though the inhibitory effects of these phenoxazines differed according to the species of mycobacteria. However these phenoxazines failed to prevent the proliferation of M. tuberculosis, M. fortuitum, and M. smegmatis, and the concerned bacteria other than mycobacteria. The present results may contribute to development of novel antibiotics against non-tuberculolsis mycobacteria.