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Biomedical subjects

Kenji Sugai

Publications and source records attributed to Kenji Sugai.

35 records · Page 2Linked to original sources
PubMed2004

Clobazam as a new antiepileptic drug and clorazepate dipotassium as an alternative antiepileptic drug in Japan.

PURPOSE: To confirm the efficacy and to clarify the problems of clobazam (CLB) as a new antiepileptic drug (AED) and clorazepate (CLP) as an alternative AED in Japan. METHODS: CLB and CLP were added on or replaced with conventional AEDs in 55 and 170 patients with refractory epilepsies, respectively. Short-term efficacy was studied after at least 2 months of CLB administration and at least 4 weeks of CLP administration. Long-term efficacy was examined in 31 cases with CLB for > or =6 months and in 86 cases with CLP for > or =6 months. CLB was initiated at 0.15-0.40 mg/kg and increased by 0.1-0.2 mg/kg every 1-2 weeks up to 0.28-1.25 mg/kg. CLP was started at 0.3-0.7 mg/kg and increased by 0.2-0.3 mg/kg every 1-2 weeks up to 2.5 mg/kg. Tolerance was examined in 42 cases with CLB for > or =3 months and 112 cases with CLP for > or =4 weeks. RESULTS: CLB was effective, defined as > or =50% reduction in seizure frequency, in 71% of the short-term subjects and 81% of the long-term subjects. Short-term efficacy was better in symptomatic localization-related epilepsies, but long-term efficacy did not differ according to seizure classification. Short-term efficacy was not different by seizure types or EEG findings. CLP was effective in 70% of the short-term subjects and 80% of the long-term subjects. CLP was more effective in patients with localization-related epilepsies or in patients with partial seizures or focal epileptiform discharges on EEG. Adverse effects developed in 47% of CLB cases and 31% of CLP cases, but the incidence was reduced by lower initial doses and slow dose titration. Tolerance occurred in 24% of CLB cases and 48% of CLP cases, half within 3-4 months after the initiation of CLB and half by 2 months after the start of CLP. Upon rechallenge, 70% of CLB-tolerant cases and 50% of CLP-tolerant cases responded to each drug again by increasing or maintaining the dosage. CONCLUSIONS: Excellent efficacy of CLB and excellent and prolonged efficacy of CLP for refractory epilepsies were confirmed. Frequent tolerance and adverse effects were major problems, but were manageable.

Anticonvulsants↗
PubMed2004

[Serial median nerve SEPs and SSEPs in patients with West syndrome].

We studied serial median nerve somatosensory evoked potentials (SEPs) and short latency somatosensory evoked potentials (SSEPs) in 17 patients with West syndrome. Four of the 7 patients with absent SEPs in the initial examination showed recognizable SEPs in the follow-up studies, associated with improvement of electroencephalogram (EEG). This indicated that SEPs were variable with condition of epilepsy and lack of initial SEPs was not always a poor prognostic factor for seizure control and developmental outcome. Persistent lack of SEPs, however, indicated poor outcome of seizures, EEG and development. Central conduction time in SSEPs did not correlate with seizure or developmental outcome.

Child, Preschool↗
PubMed2003

Six novel nonsynonymous CYP1A2 gene polymorphisms: catalytic activities of the naturally occurring variant enzymes.

Six novel nonsynonymous nucleotide alterations were found in the cytochrome P450 1A2 gene in a Japanese population, which resulted in the following amino acid substitutions: T83M, E168Q, F186L, S212C, G299A, and T438I. These individuals were heterozygous for the amino acid substitutions. The potential functional alterations caused by the amino acid substitutions were characterized by a cDNA-mediated expression system using Chinese hamster V79 cells. Among the six CYP1A2 variants, F186L showed the most profound and statistically significant reduction in O-deethylation of phenacetin and 7-ethoxyresorufin. Kinetic analyses performed for the ethoxyresorufin O-deethylation revealed that the Vmax of the F186L variant was approximately 5% of that of the CYP1A2 wild type, despite a 5-fold lower Km value of the variant, the consequence of which was reduced enzymatic activity toward the substrate. Thus, for the first time, phenylalanine at residue 186 is suggested to be a critical amino acid for catalytic activity.

Amino Acid Sequence↗
PubMed2003

Molecular genetic study in Japanese patients with Alexander disease: a novel mutation, R79L.

Since the first report by Brenner et al. of mutations in the glial fibrillary acidic protein (GFAP) gene in patients with Alexander disease, several molecular genetic studies have been performed in different ethnic groups. We previously reported a Japanese patient with a mutation, R239C, which is identical to one commonly found in American patients. Here we have analyzed four additional Japanese patients by screening for known mutations or, if no known mutation was found, by sequencing of all exons of the GFAP gene. We detected three missense mutations; one was a novel mutation, R79L, and two were previously reported mutations, R239C and R79C. All of our patients were heterozygous for their mutations. Together with the novel mutation, R79L, four different nucleotide changes altering the R79 residue have been reported, implying that any alternation of this arginine residue can give the GFAP protein a dominant negative effect, leading to accumulation of GFAP as Rosenthal fibers. We conclude that molecular genetic analysis of the GFAP gene is feasible for antemortem diagnosis of Alexander disease in Japanese patients.

Alexander Disease↗
PubMed2003

Congenital monomelic neurogenic disorder with calf muscle hypertrophy.

An 8-year-old girl had hypertrophy of the right calf muscle since birth, with progressive ankle contracture and mild muscle weakness. Her right leg was 3 cm shorter than her left. Electromyography and biopsy of the affected muscle showed neurogenic changes. She also had neurogenic bladder and spina bifida occulta at the S1 level. We believe that the spina bifida was responsible for the neurogenic changes in her right calf, but could not find definite evidence for this association. Although cases with neurogenic muscle hypertrophy, especially calf muscle hypertrophy, have been reported, none of them was congenital or associated with spina bifida occulta.

Child↗
PubMed2003

Five novel single nucleotide polymorphisms in the EPHX1 gene encoding microsomal epoxide hydrolase.

Five novel single nucleotide polymorphisms (SNPs) were found in the EPHX1 gene from 96 Japanese epileptic patients. The detected SNPs were as follows: 1) SNP, MPJ6_EX1009; GENE NAME, EPHX1 ACCESSION NUMBER, NT_004525.12; LENGTH, 25 bases; 5'-CCTCACTTCAGTG/ACTGGGCTTTGCC-3'. 2) SNP, MPJ6_EX1013; GENE NAME, EPHX1; ACCESSION NUMBER, NT_004525.12; LENGTH, 25 bases; 5'-TCCGCAGCCAGGG/CAGGACGACAGCA-3'. 3) SNP, MPJ6_EX1026; GENE NAME, EPHX1; ACCESSION NUMBER, NT_004525.12; LENGTH, 25 bases; 5'-GTTCTCCCTGGAC/TGACCTGCTGACC-3'. 4) SNP, MPJ6_EX1028; GENE NAME, EPHX1; ACCESSION NUMBER, NT_004525.12; LENGTH, 25 bases; 5'-AGGCAGGGGGACG/AGCCAGTCTTGGG-3'. 5) SNP, MPJ6_EX1030; GENE NAME, EPHX1; ACCESSION NUMBER, NT_004525.12; LENGTH, 25 bases; 5'-TGAAAAGTGGGTG/AAGGTTCAAGTAC-3'. The frequencies were 0.016 for MPJ6_EX1028 (IVS8+54G>A) and 0.005 for the other SNPs. The SNP MPJ6_EX1013 (130G>C) results in an amino acid alteration (E44Q). The other three SNPs in the coding region, MPJ6_EX1009 (30G>A), MPJ6_EX1026 (1056C>T), and MPJ6_EX1030 (1239G>A) result in synonymous changes (V10V, D352D, and V413V, respectively).

Journal Article↗
PubMed2003

[Three cases with severe motor and intellectual disabilities presenting the severest condition caused by prolonged non-convulsive status epilepticus].

Three patients with severe motor and intellectual disabilities presented deterioration of the activities of daily living, which was revealed to be caused by prolonged non-convulsive status epilepticus (NCSE). Their condition improved by the treatment with antiepileptics. Case 1, a 4-year-old girl with profound psychomotor retardation and past history of West syndrome of unknown etiology, became unable to sit and eat orally above age of two years. EEG showed continuous generalized slow spike and wave bursts indicating NCSE. Continuous intravenous infusion of midazolam abolished EEG abnormalities of NCSE, and she regained the ability of oral feeding. Case 2, a 3-year-old boy with Angelman syndrome and past history of West syndrome, presented decreased mental response, poor oral intake and somnolence. EEG showed continuous slow spike and wave bursts, indicating NCSE. High-dose phenobarbital therapy and continuous intravenous injection of vitamin B6 were effective, and remarkably improved his psychomotor activities. Case 3, a 3-year-old boy with Lennox-Gastaut syndrome, developed decreased psychomotor activity and loss of vocalization and walking. He could not sit by himself and became nearly bed-ridden. EEG showed very frequent generalized spike and wave bursts, showing NCSE. Continuous infusion of thiopental diminished NCSE, and he could walk again. Psychomotor deterioration in patients with severe motor and intellectual disabilities may be caused by NCSE, which should not be overlooked.

Child, Preschool↗
PubMed2003

[Adverse effects of dichloroacetate in a girl with mitochondrial disorder].

We present the effects and adverse effects of dichloroacetate (DCA) in a girl with mitochondrial disorder. Oral administration of DCA 50 mg/kg per day, reduced the elevated levels of lactate to below the normal range. Treatment with DCA ameliorated electroencephalogram abnormalities, but caused the adverse effects with hepatomegaly and decreased activity, which were improved by reduction or withdrawal of DCA. The decreased activity may be an adverse effect on the central nervous system. The dosage of DCA should be adjusted for each patient.

Administration, Oral↗
PubMed2003

[The parents' assessment and needs for home mechanical ventilation in patients with pediatric neurological disorders].

Parents' of patients with pediatric neurological disorders were sent a questionnaire, on their assessment and needs for home mechanical ventilation (HMV). Nine of 12 enrolled families responded. Respirator troubles were handled by a contracted HMV company. Decreased SpO2 levels and endotracheal bleeding were cared by family members under telephone instructions of doctors, though they felt anxious about dealing the problems. The mothers felt happy to live with their children by virtue of HMV, however, they had strong stress about the management of emergency care and medical care technique. They also felt very tired physically, but refreshed by being free from daily HMV care for a short time and enjoying their own time. The parents were not satisfied with the present house facilities and education system. They evaluated the induction of HMV positively but were most anxious for a better home care nursing system, doctors responding to a house call, more information on HMV, reduction of their anxieties and fatigue, and improvement of economical and educational environments.

Adolescent↗
PubMed2003

[Three cases of benign myoclonus of early infancy].

Benign myoclonus of early infancy (BMEI) is a non-epileptic paroxysmal phenomenon. Some patients with BMEI were mistakenly treated as infantile spasms, because the fits resemble to tonic spasms in infantile spasms and they occur in cluster. However, the patients have normal development and no abnormal electroencephalograms (EEG), and the fits spontaneously subside without sequelae. There are only a few reports on BMEI, and it is not widely recognized in Japan. We report three cases of BMEI. All the cases were suspected to have infantile spasms from the characteristic features of paroxysmal events, and the parents had strong anxiety because of recurrent fits. However, the fits decreased dramatically in about three months, and spontaneously disappeared within one year without any sequelae. BMEI might be included in cases of suspected infantile spasms, and such patients should be followed by monthly EEG examinations and close observation for other seizure phenomena. To avoid unnecessary treatments, such patients should be observed without any therapeutic trials including antiepileptic drugs.

Diagnosis, Differential↗
PubMed2003

[A six year-old case of narcolepsy].

We report here a 6-year-old boy with narcolepsy. The diagnostic criteria were met by the clinical symptoms including excessive daytime sleepiness and cataplexy, and by the results of overnight polysomnography (PSG), multiple sleep latency test (MSLT), and human leukocyte antigen (HLA). PSG showed increased ratio of sleep stages 1 and 2 due to frequent awakening. All the five test session of MSLT showed a sleep onset REM period. HLA typing was positive for DRB1* 1501 and DQB1* 0602. Though the present case had very early onset, all the clinical symptoms and results of sleep studies met the criteria of narcolepsy. The CSF orexin level was far below the lower limit of the control values. It is very useful to measure CSF orexin for the diagnosis of early onset narcolepsy.

Biomarkers↗
PubMed2002

Oral high-dose phenobarbital therapy for early infantile epileptic encephalopathy.

We report oral high-dose phenobarbital therapy for a patient with early infantile epileptic encephalopathy with suppression bursts (Ohtahara syndrome). At 1 month of age, many series of tonic spasms, with raising limbs and crying lasting for a few minutes, developed and increased up to approximately 300 times per day. Initially intravenous midazolam (0.5 mg/kg/hour) slightly decreased the seizures, although oral vitamin B6, valproic acid, clonazepam, and zonisamide had little effect. Oral high-dose phenobarbital therapy was begun at a dosage of 15 mg/kg/day, and the seizures markedly decreased to 5-10 times per day and the epileptic discharges on electroencephalogram greatly decreased. Serum phenobarbital levels ranged between 60 and 100 mg/dL. High-dose phenobarbital therapy should be considered for the treatment of early infantile epileptic encephalopathy with suppression bursts.

Administration, Oral↗
PubMed2002

Eleven novel single nucleotide polymorphisms in the NR1I2 (PXR) gene, four of which induce non-synonymous amino acid alterations.

Eleven novel single nucleotide polymorphisms (SNPs) were found in the NR1I2 (PXR/SXR) gene from 205 Japanese subjects. The detected SNPs were as follows: 1) SNP, MPJ6_1I2001; GENE NAME, NR1I2; ACCESSION NUMBER, AF364606; LENGTH, 25 bases; 5'-TTTCTACCTCTAC/TTATTGAAAGGGC-3'. 2) SNP, MPJ6_1I2004; GENE NAME, NR1I2; ACCESSION NUMBER, AF364606; LENGTH, 25 bases; 5'-AGGCCCAAATGTG/AAGTGATGCATAG-3'. 3) SNP, MPJ6_1I2007; GENE NAME, NR1I2; ACCESSION NUMBER, AF364606; LENGTH, 25 bases; 5'-TGCCAGGCCTGCC/TGCCTGCGCAAGT-3'. 4) SNP, MPJ6_1I2008; GENE NAME, NR1I2; ACCESSION NUMBER, AF364606; LENGTH, 25 bases; 5'-GAGTGAGCAGTGG/CGCGCGCGGGCGG-3'. 5) SNP, MPJ6_1I2010; GENE NAME, NR1I2; ACCESSION NUMBER, AF364606; LENGTH, 25 bases; 5'-CAGAGGAGCAGCG/AGATGATGATCAG-3'. 6) SNP, MPJ6_1I2011; GENE NAME, NR1I2; ACCESSION NUMBER, AF364606; LENGTH, 25 bases; 5'-CTGGAAGTGGCCA/GGGAGGTTCAAAG-3'. 7) SNP, MPJ6_1I2013; GENE NAME, NR1I2; ACCESSION NUMBER, AF364606; LENGTH, 25 bases; 5'-TCTTCCTCTCGCC/TCCCAACTTCTGG-3'. 8) SNP, MPJ6_1I2017; GENE NAME, NR1I2; ACCESSION NUMBER, AF364606; LENGTH, 25 bases; 5'-ATTGAATGCAATC/TGGCCCCAGCCTG-3'. 9) SNP, MPJ6_1I2018; GENE NAME, NR1I2; ACCESSION NUMBER, AF364606; LENGTH, 25 bases; 5'-GGTGAGCACAGCA/GGGGGGTGAGGAC-3'. 10) SNP, MPJ6_1I2019; GENE NAME, NR1I2; ACCESSION NUMBER, AF364606; LENGTH, 25 bases; 5'-GAGCTCCGCAGCA/GTCAATGCTCAGC-3'. 11) SNP, MPJ6_1I2021; GENE NAME, NR1I2; ACCESSION NUMBER, AF364606; LENGTH, 25 bases; 5'-GGTGACACCTCCG/AAGAGGCAGCCAG-3'. The frequencies were 0.0293 for MPJ6_1I2021, 0.0073 for MPJ6_1I2011, and 0.0024 for the other 9 SNPs. All SNPs were found as heterozygous. Among these SNPs, MPJ6_1I2007, MPJ6_1I2010, MPJ6_1I2017 and MPJ6_1I2019 induce non-synonymous amino acid alterations (R98C, R148Q, R381W and I403V, respectively, in PAR1).

Journal Article↗
PubMed2002

[Non-intravenous high-dose phenobarbital therapy for status epilepticus refractory to continuous infusion of midazolam or pentobarbital: report of three cases].

The management of refractory status epilepticus (RSE) is crucial in preventing neurologic impairment. Although a variety of treatments for RSE including continuous infusion of midazolam (MDL) or pentobarbital (PTB) have been carried out, they are not always effective. Intravenous very-high-dose phenobarbital (PB) has been recommended as having many advantages in the United States, but is not available in Japan. We treated 3 patients suffering from long term RSE with non-intravenous high-dose PB (NIHDPB). Their seizures were not controlled by continuous infusion of MDL and/or PTB. PB was initially given intramuscularly or rectally and then orally. Within a few or ten days, seizures were completely controlled, and consciousness level gradually improved in all cases. The serum levels of PB at seizure control ranged from 50 to 58 micrograms/ml. The epileptiform activities on EEG nearly disappeared in the absence of the burst suppression pattern. Hypotention and respiratory depression did not develop during NIHDPB. Elevated gamma-GTP levels with normal hepatic transaminases were seen in all cases, but it was not necessary to discontinue NIHDPB. NIHDPB may be one of the most effective and safe treatments in Japan for status epileptics refractory to continuous infusion of MDL or PTB.

Adult↗