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In 1965, a strange illness, which afterwards was diagnosed as the intoxication caused by organic mercury compounds, began to affect the inhabitants of the riverside areas of the Aganogawa River, Niigata, Japan. The authors have investigated the neurotological disturbances, which occurred in 144 cases intoxicated with organic mercurials. The results obtained are summarized as follows: Recruitment (in SISI and other tests) was negative in all the cases except for 32 with inner ear deafness, and Békèsy’s audiometry (TTS) showed type II: unsettled wide amplitude in 17 cases and severe abnormal adaptation characterizing the type III pattern in nine cases. Spontaneous and positional nystagmus were recorded with ENG in 94 of 144 cases. In 62 of 144 cases, pathological findings of horizontal optokinetic nystagmus were recorded, and those of vertical optokinetic nystagmus were frequently observed in 81 of the 118 cases tested (69 %). Judging from the authors’ observations, neurotological disturbances due to chronic mercurial intoxication may be considered mainly as lesions of the retrocochlea and of the oculomotor system in the brain stem and the cerebellum.

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We report a case of serotonin syndrome that occurred in a patient with chronic heart failure associated with a panic disorder. The 39-year-old Japanese man had been treated with paroxetine at 20 mg/d for 1 1/2 years. He presented with rhabdomyolysis, renal failure, fulminant liver failure, cardiac conduction disturbance, and disseminated intravascular coagulation, as well as conventional symptoms of serotonin syndrome including alterations in cognition (disorientation, confusion) and behavior (restlessness), autonomic nervous system dysfunction (fever, shivering), and abnormal neuromuscular activity (ataxia, hyperreflexia, myoclonus). All medications prescribed before hospital admission were discontinued. After 24 hours of continuous venovenous hemofiltration, diuresis resumed and renal and liver function improved rapidly. Disorientation, restlessness, hyperreflexia, and myoclonus abated slowly over the next 72 hours. The patient's anxiety subsided more slowly, and he recovered completely 1 week later. The plasma concentration of paroxetine was elevated far above the upper limit of the therapeutic range. The patient had cytochrome P-450 (CYP) 2D6*1/*5, a heterozygosity of an inactivated allele of CYP2D6, which metabolizes paroxetine. The patient was determined to be an intermediate metabolizer who was potentially vulnerable to paroxetine, a major inhibitor of CYP2D6. Heart failure is often accompanied by psychiatric disorders. A wide range of drugs commonly prescribed for these conditions, including beta-blockers, antiarrhythmics, and antidepressants, are metabolized by CYP2D6. Genetic screening for CYP2D6 in patients with these conditions may prevent life-threatening drug intoxication.

Background The prevalence of congestive heart failure (CHF) is increasing with the aging of the community. Management of patients with systolic dysfunction (SD) is important for prevention of CHF, but there is little information regarding the burden of SD on Japanese communities. Methods and ResultsIn order to delineate the epidemiological and clinical characteristics of SD patients, the medical records of patients from Sado Island were collected and summarized in 2003. From the 5 years prior to 2003, data for 497 patients were extracted. The mortality rate was significantly higher compared with the general population; and the total number of survivors had decreased to 410 by 2003. The proportion of SD patients in the general population increased sharply after the age of 65 years in males and 70 years in females, reaching 3.3% and 1.7% for men and women, respectively, in their 80 s. In 49% of the patients, the Charlson comorbidity index was ≥2, whereas 24% of females led a solitary life. Conclusions The total count of outpatients with SD is progressively increasing with age. These patients have multiple comorbidities, making the outcome of SD a poor one. The gender difference in disease characteristics and living conditions should be taken into consideration when establishing preventive strategies for CHF in Japanese communities. (Circ J 2007; 71: 1004 -1012