Isao Nishida

Attenuation of Aminoglycoside Ototoxicity by Glutathione

Aminoglycoside antibiotics are commonly used for the treatment of serious gram-negative infections despite a high incidence of associated ototoxicity. Attempts to elucidate the mechanisms of toxicity or prevent the adverse effects have previously been unsuccessful. Recently, the damaging effects of aminoglycosides on the inner ear have been shown to be caused by a metabolite of the drug, implying an enzymatic conversion of the parent compound. Glutathione has been suggested to be closely related to the detoxification mechanisms of this metabolite. This study revealed the possible attenuation of aminoglycoside ototoxicity by glutathione. Guinea pigs were given amikacin alone or amikacin with prior intramuscular injection of glutathione. The pretreatment of glutathione significantly reduced the damage of outer hair cells of the organ of Corti. This may indicate that glutathione reduces the aminoglycoside ototoxicity and can be favorably applied in clinical use.

Effect of Dosing Schedule on Aminoglycoside Ototoxicity: Comparative Cochlear Ototoxicity of Amikacin and Isepamicin

The effect of the dosing schedule on aminoglycoside ototoxicity was investigated in the guinea pig. The animals were given amikacin or isepamicin either by once-daily intramuscular injection of 200 mg/kg or by twice-daily injections of 100 mg/kg for 28 days. The once-daily treatment induced a lesser degree of ototoxicity than the twice-daily injections, which may indicate that the once-daily treatment therapy has a potential value in the clinical use of aminoglycoside antibiotics. Isepamicin sulfate is a new aminoglycoside antibiotic currently undergoing clinical investigation. This study revealed that isepamicin also has ototoxic properties as has been observed in all other aminoglycosides. The degree of ototoxicity, however, was markedly less than that of amikacin.

Cochlear fistula found in a naturally healed tympanic cavity

A cochlear fistula found in a naturally healed mastoid cavity is reported. The patient is a 53-year-old Japanese woman who was complaining of unsteadiness. She had a long history of otorrhoea in childhood. Her tympanic and mastoid cavities were widely open and were covered by thin epithelium. The posterior wall of the ear canal was missing. She had no hearing in the ear but responded to electrical promontory testing. Exploratory surgery was indicated at which fistulae of the basal turn of the cochlea and the horizontal semicircular canal were found. These fistulae were sealed by pieces of bone and muscle.

Low Dose Long Term Clarithromycin Therapy for Chronic Sinusitis in Children.

Long terme rythromicin (EM) therapy has been reported to be useful in chronic sinusitis. We investigated the clinical effectiveness of low dose long term clarithromycin (CAM) therapy for chronic sinusitis in children. Children were treated with 100 or 200mg of CAM perday for 4 to 18 weeks.1) Total clearing of subjective symptons was revealed in 93.8% of the patients.2) Total improvement rates were 93.8% for rhinoscopic findings and 90.6% for X-ray appearance.3) The clinical effectiveness of CAM therapy tended to be better than that of EM therapy.4) No significant side effects were noted during the therapy.It is the refore concluded that CAM therapy is very useful in the treatment of chronic sinusitis in children.

Aminoglycoside Ototoxicity Reduced by Glutathione in Guinea Pigs.

Aminoglycoside antibiotics are commonly used in the treatment of serious gram negative infections despite a high incidence of associated ototoxicity. Attempts to elucidate the mechanism of the toxicity or prevent the adverse effects have so far been unsuccessful. Recently the damaging effects of aminoglycoside on the inner ear have been shown to be caused by a metabolite of the drug, implying an enzymatic conversion of the parent compound and glutathione has been suggested to be closely related to the mechanism of detoxication of this metabolite. This study demonstrates the attenuation of aminoglycoside ototoxicity by glutathione. Guinea pigs were given amikacin or amikacin+glutathione by intramuscular injection. Pretreatment with glutathione significantly reduced damage to the outer hair cells of the organ of Corti. This finding suggests that glutathione can reduce aminoglycoside ototoxicity and that it can be considered for clinical use.

Long-term results of treatment for carcinoma of the maxillary sinus.

Seventy-three patients with previously untreated carcinoma of the maxillary sinus, treated during an 11-year period were investigated retrospectivelyThe overall three-year and five year survival rates were 51.5% and 42.7% respectively. The five-year survival rate for the group treated with combined therapy consisting of local chemotherapy, radiation and necrotomy was 12.9%, it was 54.8% in the group treated with combined therapy followed by surgery, such as partial or total resection of the maxilla.The most successful treatment was intraarterial infusion of adriamycin (bolus) and 5-FU (continuous), combined with radiotherapy and necrotomy, followed by surgery. The five-year survival rate in this group was 61.7%.