Pharmacokinetic Study on Excretion of Inorganic Fluoride Ion, a Metabolite of Sevoflurane

Blood and urinary inorganic fluoride ion concentration was determined in six healthy volunteers after inhalation of 2% sevoflurane for one hour. The serum inorganic fluoride ion concentration increased 30 min after discontinuation of inhalation to 14.8 ± 3.0 μmol/liter, which was about 10 times higher than the level before inhalation. The serum elimination constant of inorganic fluoride was calculated to be 0.000467 and the half-life was 1,487 min. The urinary excretion rate of inorganic fluoride ion was the highest ( 452 nmol/min) after 12-24 hr. The urinary excretion rate constant of inorganic fluoride was calculated to be 0.000268 and the half-life was 2,583 min. The distribution volume of inorganic fluoride excreted in the urine was calculated to be 127 liters. This value showed that fluoride ion produced in the cell cannot readily pass through the cell membrane due to its polarity, resulting in a delay of the maximum excretion rate of inorganic fluoride until the first or second day after inhalation of the anesthetic.This study was supported in part by a Grant-in-aid for Science Research from the Ministry of Education, Science and Culture of Japan and a Grant-in-aid from the Association for the Advancement of Medicine of the Tsuchiya Foundation

Genetic Analysis with Calcium-induced Calcium Release Test in Japanese Malignant Hyperthermia Susceptible (MHS) Families

Some genetic studies have shown a linkage between malignant hyperthermia susceptibility (MHS) and chromosome 19q or the skeletal muscle ryanodine receptor (RYR1) gene. Some types of MHS seem to be caused by an abnormality of calcium-induced calcium release (CICR). We analyzed the linkage of RYR 1 gene polymorphisms in Japanese MHS families and investigated the correlation between genetic evidence of RYR1 gene mutations and an accelerated rate of CICR.　　 We studied 63 subjects who were referred to our institute for investigation of MHS. CICR rates were measured by the skinned fiber method in 23 subjects. DNA samples were collected from 63 individuals belonging to 22 unrelated families. Restriction fragment length polymorphism (RFLP) analyses on the RYR1 locus and hypervariable microsatellite analysis were performed.　　 We found one family with a linkage between acceleration of the CICR mechanism and a group of RFLPs. In CICR tests, ten of the 11 patients who had presented with fulminant MH showed accelerated rates of CICR. Analysis for the mutation C1840T, which was performed in 63 samples, did not demonstrate an alteration in any of the patients. Although we found heterozygotes in RFLP studies, we did not recognize a specific relationship between the acceleration of CICR and the RFLPs.　　 We suggest a linkage between the acceleration of CICR and an abnormal human RYR1 gene in MHS. These results also suggest that heterogeneity exists for MH. We conclude that genetic tests cannot replace CICR tests or caffeine-halothane contracture tests with muscle biopsy as a diagnosing test for MH in the near future.This work was partly supported by grants-in-aid from the Ministry of Education, Science and Culture of Japan (No.08407052: Osafumi Yuge, No.09771157: Yasuhiro Maehara) and by a research grant from the Labor Welfare Corporation of Japan

Gene therapy for spinal muscular atrophy is considerably effective when administered as early as possible after birth

Introduction: Spinal muscular atrophy (SMA) is a neuromuscular disease characterized by muscle atrophy and progressive muscle weakness. Insurance-approved treatments in Japan include antisense oligonucleotide therapy, gene therapy, and small molecule therapy. The efficacy of these therapies varies depending on the timing of treatment initiation. Case presentation: We report the cases of two infants with SMA born in the same region. Patient 1, who had two copies of SMN2, was born before newborn screening (NBS) was started and received onasemnogene abeparvovec therapy at the age of 4 months. Patient 2, who had three copies of SMN2, was born after the start of NBS and was diagnosed and treated with onasemnogene abeparvovec before symptoms appeared. Unfortunately, Patient 1 became bedridden despite receiving gene therapy, while Patient 2 achieved normal motor development. Discussion: Our findings show that treatment timing is an essential factor affecting patients' motor neurodevelopmental outcomes, although our patients did have differences in the number of copies of SMN2. Therefore, a system should be established to allow all newborns to undergo publicly funded NBS for SMA

Support for Childcare Stressors of Parents with “Children of Concern”

要　　旨 発達の気になる子どもを担当する保育士に対して，親の育児ストレスをふまえた親理解や具体的な親支援についてアンケート調査を実施した． 保育士がふだんの関わりで感じていた担当児の保護者の様子と育児ストレス結果との相違点について，子どもに関する育児ストレスの側面については保育士全体の87.5％がほぼ一致していたと回答した． 一方で，親自身に関する育児ストレスの側面についてほぼ一致していたと回答した者は25％であった． 保護者支援に関しては，対象者の全員が親の育児ストレス調査は保護者理解および支援に有効であると回答した．母への直接的な対応については経験年数にかかわらず記述があった一方で，子どもの発達理解を含めた対応について記述しているものは経験年数が17 年目以上の保育士であった． 発達の気になる子どもをもつ保護者支援を行う際の保育士自身への支援として，育児ストレスの情報は有用であると考える．departmental bulletin pape