Jun Kusakari

The Effect of Methylprednisolone on Acoustic Trauma

The effect of methylprednisolone (mPSL) upon acoustic trauma was studied using albino guinea pigs which were exposed to 2 kHz pure tone of 110, 115 or 120 dB SPL for 10 min. After the exposure to intense sound, mPSL of 6, 12 or 40 mg/kg was intraperitoneally given daily for 7 days and the threshold of the compound action potential (CAP) was examined on the 8th day. Compared with CAP of the control animals given physiological saline solution, no significant difference was observed in the CAP threshold shift between the mPSL group and the controls following exposures to the sound of 115 and 120 dB SPL, respectively. However, when the animals were exposed to the sound of 110 dB SPL, the CAP threshold shift was significantly smaller in the mPSL animals than in the controls. The present results indicate that mPSL possesses a therapeutic effect in cases of mild acoustic overstimulation.

Proton Therapy for Head and Neck Malignancies at Tsukuba

Purpose:To evaluate the effectiveness and feasibility of proton therapy for head and neck cancers.Patients and Methods:From 1983 to 2000, 33 patients with head and neck malignancies but no history of surgical resection were treated with 250-MeV protons with or without X-ray irradiation. This study retrospectively evaluated local control, survival, and treatment sequelae of these patients. The median total target dose using protons with or without X-rays was 76 Gy (range: 42–99 Gy) and the median proton dose per fraction 2.8 Gy (range: 1.5–6.0 Gy).Results:Overall 5-year survival and local control rates were 44% and 74%, respectively. One (3%) and six patients (18%) suffered from treatment-related acute and late toxicity > grade 3 (RTOG/EORTC acute and late radiation morbidity scoring criteria). One patient with a history of radiotherapy suffered from acute toxicity > grade 3.Conclusion:Proton therapy appeared to offer high local control rates with few toxicities relative to conventional radiotherapy. However, late toxicity was seen in areas where large radiation doses had been given.Ziel:Prüfung der Wirksamkeit und Durchführbarkeit einer Protonentherapie bei Kopf-Hals-Malignomen.Patienten und Methodik:Von 1983 bis 2000 wurden 33 Patienten mit Kopf-Hals-Malignomen, aber ohne chirurgische Vorbehandlung mit 250-MeV-Protonen mit oder ohne Röntgenstrahlung behandelt. Diese Studie wertet retrospektiv lokale Kontrolle, Überleben und Therapiefolgen aus. Die mediane Gesamtdosis bei Anwendung von Protonen mit oder ohne Röntgenstrahlung betrug 76 Gy (Spanne 42–99 Gy), und die mediane Protonenfraktionsdosis war 2,8 Gy (Spanne 1,5–6,0 Gy).Ergebnisse:Die Fünf-Jahres-Überlebens- und Lokalkontrollraten betrugen 44% bzw. 74%. 1 (3%) und 6 (18 %) Patienten litten unter therapiebedingten Akut- und Langzeitnebenwirkungen höher als Grad 3 (RTOG/EORTC-Kriterien für Akut- und Langzeitstrahlennebenwirkungen). 1 Patient mit vorausgegangener Strahlentherapie erlitt akute Nebenwirkungen höher als Grad 3.Schlussfolgerung:Die Protonentherapie führte zu hohen Raten lokaler Kontrolle bei—verglichen mit konventioneller Radiotherapie—geringen Nebenwirkungen. Allerdings wurden Langzeitnebenwirkungen in Arealen beobachtet, die hoher Strahlungsdosis ausgesetzt gewesen waren.

The effect of mannitol upon cochlear dysfunction induced by transient local anoxia

Transient local anoxia of the cochlea was induced by pressing the labyrinthine artery, and compound action potential (CAP) or endocochlear potential (EP) was measured before and after transient local anoxia ranging from 5 to 60 min using 106 albino guinea pigs. The complete interruption of the cochlear blood flow by this procedure and its full restoration after releasing the pressure on the artery was confirmed by a laser-Doppler flowmeter. The anoxia of less than 10 min induced no post-anoxic cochlear dysfunction, whereas the anoxia of a longer duration induced an irreversible dysfunction of the cochlea. It was evident that the post-anoxic recovery of the CAP threshold was worse as the anoxia period was prolonged, and CAP was almost completely abolished after 60-min anoxia. In animals which were administered mannitol intravenously just after the restoration of the cochlear blood circulation, the recovery of the CAP threshold was significantly better than that in the control animals, when the animals were subjected to local anoxia of 15- to 30-min duration. No beneficial effect, however, was observed in the 60-min anoxia group. In conclusion, local anoxia of 10 min or longer caused cochlear dysfunction, which was partially but significantly alleviated by mannitol.

Nonsyndromic hearing loss caused by a mitochondrial T7511C mutation

Objectives The aims of the present study were to identify a mutation in a Japanese family showing nonsyndromic sensorineural hearing loss and to relate the mutation to characteristics of patients, including audiovestibular findings.

Determination of prednisolone in the cochlear tissue.

Although glucocorticoids are widely used to treat inner ear diseases, glucocorticoid concentration has never been determined in the cochlear tissue. The aim of the present study was to measure the prednisolone concentration in the cochlear tissue after intravenous administration. At 0.5, 1, 2, 4 or 8 h after the injection (100 mg/kg), cochlea, hepatic and brain tissue and serum were removed, and prednisolone extracted from these samples was measured using high-performance liquid chromatography. Although prednisolone was not detected in the brain tissue, it was detected in the hepatic tissue and serum, demonstrating the peak value at 30 min after administration and a rather rapid decline with time thereafter. Prednisolone was also detected in the cochlear tissue, but the uptake and elimination patterns were entirely different from other samples. The prednisolone level in the cochlea reached the peak value 1 h after administration and gradually declined. The present study shows that the prednisolone administered is gradually transported to the cochlear tissue from blood and remains at higher concentrations than in the hepatic tissue or serum over several hours. It is highly likely that this slow elimination is closely related to the therapeutic effect of steroids in inner ear diseases.

Steroid-sensitive nephrotic syndrome associated with Kimura disease.

Abstract We report an 11-year-old Japanese boy with Kimura disease and associated nephrotic syndrome. Before the diagnosis of Kimura disease was established, the patient had three episodes of swelling on the left cheek with subsequent nephrotic syndrome. Steroids were effective for both conditions. However, both conditions recurred within months of discontinuation of steroids. For the fourth episode of swelling on the left cheek, cyclosporine (CsA) was used. The subcutaneous tumor responded to CsA and disappeared within a few days. There has been no subsequent relapse of the nephrotic syndrome to date.

Outer hair cells functionally and structurally deteriorate during reperfusion

Transient ischemia of the cochlea was induced in 65 albino guinea pigs by pressing the labyrinthine artery, and the effects of cochlear reperfusion on cochlear potentials (endocochlear potential, compound action potential and cochlear microphonics (CM)) and structural changes in hair cells were examined. Although 15 min ischemia did not elevate the post-ischemic CM pseudo-threshold as compared with the pre-ischemic value, ischemia of 30 min or longer significantly elevated the CM pseudo-threshold. CM amplitude tended to progressively decrease during the reperfusion period in the animals subjected to 45 or 60 min ischemia. After transient ischemia, outer hair cells (OHCs) were swollen and exhibited alterations of the nucleus. Severer structural deterioration of OHCs was induced by 4 h reperfusion than ischemia itself when the ischemic period was 45 or 60 min. Perilymphatic perfusion of dimethylthiourea, a hydroxyl radical scavenger, partially ameliorated the elevation of the CM pseudo-thresholds and the structural changes of OHCs. These results indicate that cochlear reperfusion induces functional and structural deterioration of OHC probably by hydroxyl radical generation.

Effect of nitric oxide synthase inhibitor on cochlear dysfunction induced by transient local anoxia

To evaluate whether nitric oxide (NO) plays a role in the mechanism of generation of cochlear dysfunction induced by anoxia and reperfusion, the effects of a nitric oxide synthase (NOS) inhibitor, N-nitro-L-arginine, were examined using 71 albino guinea pigs. Transient cochlear anoxia of different duration (15, 30 or 60 min) was induced by pressing the labyrinthine artery and compound action potential (CAP) was measured before and 4 h after anoxia. N-nitro-L-arginine (1-30 mg/kg) administered intraperitoneally 1 h before the onset of anoxia alleviated the cochlear dysfunction when the anoxic period was 15 or 30 min. No beneficial effect was observed, however, in the 60-min anoxia. These results indicate that NO contributes to the generation of anoxia-induced cochlear dysfunction and that NOS inhibitor has a protective effect on the cochlear injury induced by anoxia of moderate duration.

Ischemia-reperfusion injury of the cochlea: effects of an iron chelator and nitric oxide synthase inhibitors

Release of free iron from cellular stores and activation of nitric oxide synthase (NOS) has been implicated in a wide variety of cochlear injuries. In order to evaluate the effects of deferoxamine (a iron chelator), 3-bromo-7-nitroindazole (a relatively selective neuronal NOS (nNOS) inhibitor) or aminoguanidine (a relatively selective inducible NOS (iNOS) inhibitor) on the post-ischemic cochlear dysfunction, albino guinea pigs were subjected to 30 min ischemia, and the threshold shifts of the compound action potential (CAP) from pre-ischemic values were compared with those of control animals 4 h after the onset of reperfusion. A statistically significant reduction in the post-ischemic CAP threshold shift was observed in the animals treated with deferoxamine or 3-bromo-7-nitroindazole. However, aminoguanidine did not affect the post-ischemic CAP threshold shift. These results suggest that free iron and nNOS play deleterious roles in the cochlear injury induced by transient ischemia.

Long-term observations on the reversibility of cochlear dysfunction after transient ischemia

To examine the reversibility of functional damage to the cochlea after transient ischemia, cochlear ischemia of 0-60 min was induced in 34 albino guinea pigs. Thresholds of auditory brainstem response (ABR) were then followed for 5 days after ischemia. Although the ABR threshold returned to almost the pre-ischemic value after 15 min ischemia, ischemia of 30 and 60 min duration induced irreversible dysfunction. Aminoguanidine, an inducible NO synthase (iNOS) inhibitor, significantly ameliorated the post-ischemic cochlear dysfunction induced by 60 min ischemia. Morphological findings of the hair cells were consistent with these functional results. These results indicate that ischemia of 30 min or longer induces irreversible damage to the cochlea and that iNOS plays injury-producing roles in this type of injury.