Biomedical subjects
Publications and source records attributed to T Nobori.
A simple synthesis of adenylyl-(2'----5')-adenylyl (2'----5')-adenosine (2-5A core) has been achieved on the basis of selective 3'-O-silylation of 5'-O-p-monomethoxytrityladenosine and chemo-selective formation of the 2'-5' internucleotide linkage using N-unprotected nucleosides.
Pharmacokinetics of ceftizoxime (CZX), a new cephalosporin antibiotic, was investigated in 9 children with normal renal and hepatic function. In addition, the clinical effect of CZX was evaluated in 26 pediatric patients with various infections. In 4 of the 9 children with normal renal and hepatic function, intravenous bolus injection of CZX in a dose of 20 mg/kg yielded a mean peak serum level of 36.5 micrograms/ml at 1/2 hour after infusion, and mean serum levels of 12.5 micrograms/ml at 2 hours and 6.0 micrograms/ml at 4 hours after infusion. The biological half-lives of CZX were estimated to be 1.25--2.55 hours. In another child, serum levels of CZX at 1/2, 2 and 4 hours after intravenous bolus injection in a dose of 10 mg/kg were 19.60, 5.96 and 2.06 micrograms/ml, respectively. The clear difference in dose response between 20 mg/kg and 10 mg/kg reflected the doubled dose levels. In the remaining 4 children, drip infusion of CZX in a dose of 20 mg/kg (1 child 17 mg/kg) over 0.5--1.5 hours yielded peak serum levels at the end of infusion. The biological half-lives of CZX were estimated to be 0.95--1.50 hours. About 80% of CZX was excreted in the urine within 6 hours after infusion in the 4 children tested. Twenty-six pediatric patients with various infections were treated with CZX intravenous doses of 20 mg/kg to 118 mg/kg b.i.d.--q.i.d. for 3--14 days. Of the 12 patients with acute bronchitis and pneumonia, 5 showed excellent response, 6 good and 1 fair response. Of the 5 patients with urinary tract infection, 4 showed excellent response and 1 good response. One patient each with colitis, tonsillitis and facial cellulitis, pharyngitis showed excellent response and 1 patient each with purulent thyroiditis and gluteal abscess showed good response. The single patients with sepsis showed excellent response. One patient each with pyothorax, purulent arthritis and cerebral abscess showed poor response. Overall effectiveness rate was 84.6%. although 22 of all 26 patients treated had serious underlying diseases such as APL, AML. A mild increase in GOT and GPT was observed in 1 patient during treatment with CZX, and the values returned to normal after discontinuation of the drug. These results suggest that ceftizoxime is 1 of the most important antibiotics for treating a wide range of infections in children as well as in adults.
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Thirteen patients with malignant solid tumors, mainly osteogenic sarcomas, were treated by high-dose MTX therapy, 50-400 mg/kg, in a total of 72 cycles. It has been proved that this therapy was relatively safe provided careful clinical surveillance were assured. Of 8 patients with osteogenic sarcomas, 6 had no metastatic lesions on the chest X-rays before this therapy: three were alive without any evidence of disease for 18-25 months after high-dose MTX therapy. In some cases of other malignant solid tumors, particularly intracranial tumors, clinical efficacy was observed. Dose-time relationships, etc. should further be studied for more therapeutic efficacies of high-dose MTX therapy.
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