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Intravenous acute and subacute toxicity studies of 6315-S (flomoxef), a new oxacephem antibiotic, were conducted in beagles. Acute toxicity study: Dogs received as a single i. v. infusion 1, 250 ... mg/kg, 2, 500 mg/kg or 5, 000 mg/kg, of 6315-S or 1, 250 mg/kg, or 2, 500 mg/kg of CEZ as a reference compound. They tolerated 6315-S up to 5, 000 mg/kg, while one of three dogs died after administration of 2, 500 mg/kg of CEZ. Toxic signs were salivation, vomiting and defecation during and immediately after infusion of 6315 -S or CEZ, these signs being more prominent in the CEZ-treated dogs. An other finding was hematuria, which was observed in the dogs treated with 2, 500 mg/kg or more of 6315-S. Subacute toxicity study: Dogs received 0 (saline), 250 mg/kg, 500 mg/kg or 1, 000 mg/kg of 6315-S, or 1, 000 mg/kg of CEZ i. v. for one month. All dogs tolerated treatment withboth substances. Salivation, vomiting and defecation were observed in those receiving 1, 000 mg/kg of 6315-S or CEZ. Hematological examination revealed a decrease in platelet count and prolonged clotting time in a few dogs receiving more than 500 mg/kg of 6315-S or 1, 000 mg/kg of CEZ, but the changes were slight and dose-unrelated. The main histological finding was inflammatory reaction at the injection site of all dogs, including the saline-treated group. The results showed that the maximum tolerated dose of 6315 -S in the acute toxicity study was more than 5, 000 mg/kg and the maximum no-effect dose in the one-month toxicity study was 250 mg/kg/day. more

背景：在宅で生活する乳幼児期の先天性心疾患児は，計画外に入院することがある．計画外入院を防ぐ支援を検討するためには，原因を明らかにする必要があると考え，患児数や原因などの実態を調査した．方法：A病院で5年間に入院歴のある乳幼児期の先天性心疾患児のDPCと診療記録を対象にデータ収集し分析を行った．結果：乳幼児期の先天性心疾患児の35.4％が計画外入院を要した．そのうち，0歳児は31.7％と有意に多く，染色体異常を合併する患児が多かった．主な原因は，肺炎や気管支炎などの呼吸器合併症，心不全，SpO2低下やチアノーゼ，低酸素血症などを含む呼吸状態の悪化であった．在宅酸素療法は50.3％，在宅人工呼吸療法は7.9％，在宅経管栄養療法は26.0％で使用していた．結論：先天性心疾患児の計画外入院は，0歳児が最も多く，先天性心疾患による体肺循環の障害に加え，呼吸機能と循環機能の未発達さや脆弱性による影響があった．計画外入院を防ぐためには，病院から在宅と切れ目のない支援，訪問看護などの医療職の支援が必要である．

The toxicity of tobramycin, a new aminoglycoside antibiotic, when administered to beagle dogs by daily consecutive intramuscular injections for 28 days was studied and compared with that of ... gentamicin. Recovery tert after withdrawal of the drug was performed for a month after the 28 days administration. No significant findings appeared in behavior, hematologic and biochemical parameters except slight loss of hearing in 2 of 8 dogs given tobramycin 15 mg/kg/day. There was no histologic evidence of the drug effect in any organs, other than muscular injuries at the injection sites. All dogs given 30 mg/kg/day showed reduction of locomotor activity and weight loss after day 21. In the terminal stage, 25 to 26 days, disappearance of neurological reflexes, abnormal ECG, convulsions and prostration were noted in 2 of 4 female dogs. Such elevations of the BUN and the creatinine values with the decrease or Ca ion content in blood plasma as those of uremic syndroms developed in all the dogs on this regimen. Histological examination revelaed that the renal cortical tubular necrosis with concomitant epithelial regeneration and the necrosis of muscle fibers at the injection site were comparable, qualitatively and quantitatively, to those obtained in the gentamicin 15 mg/kg/day group. However, these changes returned to the normal rapidly after the withdrawal of the drug. All dogs administered gentamicin 30 mg/kg/day showed marked alteration of renal function on about day 20 with the most severe necrosis of proximal convoluted tubules of all the dogs examined and became moribund due to uremia. more