Shigetaka Shimizu

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.

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.

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 Cushings 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.

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 μg (7.5 μl) 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.

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.

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

Abstract Conclusion: Blockage of the endolymphatic duct is a significant finding in Menieres 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 Menieres disease. Objective: Comparison of blockage of the longitudinal flow of endolymph between ears affected by Menieres disease and normal ears. Methods: We examined 21 temporal bones from 13 subjects who had Menieres disease and 21 normal temporal bones from 12 controls. Results: The endolymphatic duct was blocked in five (23%) ears affected by Menieres disease (p = 0.016). The utricular duct was blocked in 16 (76%) ears affected by Menieres disease and 11 (52%) normal ears (p = 0.112). The saccular duct was blocked in 6 (28%) of ears affected by Menieres disease and 16 (76%) normal ears (p = 0.001). The ductus reuniens was blocked in 10 (47%) ears affected by Menieres disease and 10 (47%) normal ears (p = 1.000).

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

Abstract 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 Menieres 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.

Effect of cupula shrinkage on the semicircular canal activity.

Abstract 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.

Efficacy of physical therapy for intractable cupulolithiasis in an experimental model.

OBJECTIVE To investigate what kinds of stimuli are effective in detaching otoconia from the cupula in three experimental models of cupulolithiasis. METHODS Three experimental models of cupulolithiasis were prepared using bullfrog labyrinths. Three kinds of stimuli were applied to the experimental models. In experiment one (gravity), the labyrinth preparation was placed so that the cupula-to-crista axis was in the horizontal plane with the canal side in the downward position. In experiment two (sinusoidal oscillation), the labyrinth preparation was placed 3 cm from the rotational centre of a turntable, which was sinusoidally rotated with a rotational cycle of 1 Hz and a rotational angle of 30°. In experiment three (vibration), mechanical vibration was applied to the surface of the bony capsule around the labyrinth using a surgical drill. RESULTS In experiments one, two and three, the otoconial mass was respectively detached in 2 out of 10 labyrinth preparations, none of the labyrinth preparations, and all of the labyrinth preparations. CONCLUSION Vibration was the most effective stimulus for detaching the otoconia from the cupula in these experimental models of cupulolithiasis.

Relationship between clinical features and therapeutic approach for benign paroxysmal positional vertigo outcomes.

OBJECTIVE To examine the clinical features, age and gender distribution of patients, treatment methods, and outcomes of benign paroxysmal positional vertigo. METHODS This paper reports a review of 357 patients treated for this condition at a single institution over a duration of 5 years. Patients with posterior canal benign paroxysmal positional vertigo were divided into two groups: one group underwent the Epley manoeuvre and the other received medication. The lateral canal canalolithiasis patients were also divided into two groups: one underwent the Lempert manoeuvre and the other received medication. Lastly, the lateral canal cupulolithiasis patients were treated with medication and non-specific physical techniques. RESULTS AND CONCLUSION For patients with posterior canal benign paroxysmal positional vertigo, resolution time was significantly shorter in the Epley manoeuvre group than in the medication group. For the lateral canal canalolithiasis patients, resolution time was significantly shorter in the Lempert manoeuvre group than in the medication group. Resolution time was significantly longer in the lateral canal cupulolithiasis patients than in the other patients. The average age of patients increased with the number of recurrences, as did predominance in females. Average age and rate of sensorineural hearing loss were significantly higher in patients with intractable benign paroxysmal positional vertigo compared with those in the curable benign paroxysmal positional vertigo group.