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Biomedical subjects

N Yasui

Publications and source records attributed to N Yasui.

At least 73 records · Page 4Linked to original sources

Postoperative anticonvulsant prophylaxis for patients treated for cerebral aneurysms.

The incidences of postoperative seizures and side effects were evaluated in 193 patients with cerebral aneurysm who received anticonvulsant prophylaxis and underwent 224 craniotomies for cerebral aneurysms between 1993 and 1995. The patients were 73 males and 120 females aged between 31 and 80 years. One hundred and sixteen patients had ruptured cerebral aneurysms and 108 had unruptured aneurysms. Phenytoin followed by valproic acid were administered. Early postoperative seizures occurred in five patients (4 with ruptured and 1 with unruptured aneurysms) within 14 days after surgery. Late postoperative seizures occurred in four different patients with ruptured aneurysms more than 14 days after surgery. The presence of cortical lesions detected by cerebral computed tomography and occurrence of symptomatic vasospasm were correlated with the occurrence of early postoperative seizure (p < 0.05). Three of the four patients with late postoperative seizure had cortical lesions and two were receiving continued medication. Side effects that warranted discontinuation of therapy were seen in the follow-up period in 12.9% of patients. Anticonvulsant prophylaxis is not recommended due to the higher incidence of side effects than seizure, except in patients in poor clinical condition for the purpose of brain protection. Otherwise, anticonvulsant medication should be initiated at the time of the initial seizure attack.

Adult↗

Histological changes in the rat common carotid artery following simultaneous topical application of cotton sheet and cyanoacrylate glue.

Histological changes in and around the arterial walls of rats were investigated following simultaneous topical application of cotton sheet and cyanoacrylate glue. The bilateral common carotid arteries were exposed using sterile techniques, and the test materials were applied to the right artery. The left artery served as a control. Changes in arterial histology were evaluated at 2 weeks, 1 month, 2 months, and 3 months after surgery. Extensive inflammation consisting primarily of histiocytes and multinuclear giant cells was observed around the materials, but tended to decrease by 3 months. Necrosis in the media and fibrosis in the adventitia initially appeared around 2 weeks, and became advanced by 2-3 months. At 2-3 months, disruption of elastic fibers and marked fibrosis in the media were seen, and endothelial proliferation in the intima appeared. Intimal proliferation was observed at both the experimental and other sites of the vessels. The present results suggest that simultaneous use of the test materials can cause the arterial occlusive lesions observed following aneurysmal surgery.

Animals↗

How should a subarachnoid hemorrhage grading scale be determined? A combinatorial approach based solely on the Glasgow Coma Scale.

OBJECT: The purpose of this study was to present a combinatorial approach used to develop a subarachnoid hemorrhage (SAH) grading scale based on the patient's preoperative Glasgow Coma Scale (GCS) score. METHODS: There are 4094 different combinations that can be used to compress the 13 scores of the GCS into two to 12 grades. Break points, the positions in the scale in which two adjacent scores connote a significantly different outcome, are obtained by a direct comparison of the GCS and the Glasgow Outcome Scale (GOS). Guided by the break points, the number of combinations to be considered can be limited. All possible combinations are statistically analyzed with respect to intergrade differences in outcome. Single combinations, with the maximum number of grades having maximum intergrade outcome differences for each corresponding set of adjacent grades, must be selected. The authors verified the validity of this combinatorial approach by retrospectively analyzing 1398 consecutive patients with aneurysmal SAH who underwent surgery within 7 days of the last hemorrhage episode. The patients' GCS scores were assessed just before surgery and their GOS scores were estimated 6 months post-SAH. The combinatorial approach yields only one acceptable grading scale: I (GCS Score 15); II (GCS Scores 11-14); III (GCS Scores 8-10); IV (GCS Scores 4-7); and V (GCS Score 3). CONCLUSIONS: The combinatorial approach, guided by the break points, is so simple and systematic that it can be used again in the future when revision of the grading scale becomes necessary after development of new and effective treatment modalities that improve patients' overall outcome.

Age Factors↗

Correction of knee deformity in patients with Ellis-van Creveld syndrome.

Six knees in three patients with Ellis-van Creveld syndrome were treated with lateral soft tissue release and corrective osteotomy of the tibia at 10 years of age on average. The main feature was valgus deformity with lateral dislocation of the patella. All patellae were reduced. The valgus deformity improved from 35 degrees (range, 48 degrees-20 degrees) to 17 degrees (range, 35 degrees-5 degrees) of the femorotibial angle (FTA) on average, although the FTA in five of six knees was < 5 degrees after surgery. There was one recurrent case and one transient peroneal nerve palsy. The reason for undercorrection was a depression of the lateral tibial plateau. The deformity of the articular surface is the most important problem in correcting the valgus deformity of the knee in this syndrome.

Adolescent↗

Laparoscopically assisted bowel resection for primary mucosa-associated lymphoid tissue lymphoma of the cecum.

We present the first report of laparoscopic resection for colorectal mucosa-associated lymphoid tissue (MALT) lymphoma. A 76-year-old man was found to have MALT lymphoma of the cecum during colonoscopy. He underwent a laparoscopically assisted ileocecal resection after admission and was discharged 9 days postoperatively without any complications. Colorectal MALT lymphoma is a rare neoplasm that responds favorably to locally directed therapy, because it tends to remain localized for prolonged periods. Laparoscopic surgery for colorectal MALT lymphoma is considered feasible because it is minimally invasive, making it suitable for treatment of low-grade malignancies, such as MALT lymphoma, which cannot be removed endoscopically.

Aged↗

Transcriptional regulation of osteopontin gene in vivo by PEBP2alphaA/CBFA1 and ETS1 in the skeletal tissues.

Osteopontin (Opn) and polyoma enhancer-binding protein (PEBP) 2alphaA/core binding factor (CBFA) 1 have been suggested to play important roles in ossification. The overlapping localization of opn and PEBP2alphaA/CBFA1 mRNA, and the marked decrease of opn mRNA expression in PEBP2alphaA knockout mice, indicated that the transcription of opn gene was controlled by PEBP2alphaA. In the present study, we determined the direct regulation of PEBP2alphaA on the opn promoter activity. Opn promoter activity was markedly enhanced by PEBP2alphaA and ETS1 in a synergistic manner. The synergistic effect was diminished when either the PEBP2alphaA or ETS1 binding site was mutated, or the spatial arrangement of these sites was mutated by a 4-nt insertion. The distance between these sites was important for transactivation but not protein-DNA binding. The direct interaction between PEBP2alphaA and ETS1 was depended on protein-DNA binding. These results suggested that the specific spatial arrangement of both sites and direct interaction between PEBP2alphaA and ETS1, were essential for promoter function. Furthermore, endogenous opn mRNA was decreased with the introduction of dominant negative PEBP2alphaA to MC3T3/E1 cells expressing endogenous PEBP2alphaA, ETS1 and opn. These findings suggest that PEBP2alphaA and ETS1 cooperate in vivo to regulate expression of the opn gene in the skeletal tissue. Cell type-specific regulation of Opn gene expression will also be discussed.

3T3 Cells↗

High-performance liquid chromatographic determination of nemonapride and desmethylnemonapride in human plasma using an electrochemical detection.

A high-performance liquid chromatographic method using an electrochemical detector (HPLC-ED) was developed for the determination of nemonapride and its active metabolite, desmethylnemonapride in human plasma. Nemonapride, desmethylnemonapride and moperone chloride, which was used as the internal standard (I.S.) in plasma, were extracted by a rapid and simple procedure based on C18 bonded-phase extraction, and were separated by C8 reversed-phase HPLC column. Nemonapride and desmethylnemonapride were detected by high conversion efficiency amperometric detection at +0.84 V. Determination of both nemonapride and desmethylnemonapride were possible in the concentration range at 0.25-5.0 ng/ml, and the limit of detection for each was 0.1 ng/ml. The recoveries of nemonapride and desmethylnemonapride added to plasma were 97.0-98.2% and 96.7-98.8%, respectively, with coefficients of variation of less than 7.2% and 10.3%, respectively. This method is applicable to drug level monitoring in the plasma of schizophrenia patients treated with nemonapride and to the study of pharmacokinetics.

Antipsychotic Agents↗

Splicing patterns of type XI collagen transcripts act as molecular markers for osteochondrogenic tumors.

Primary transcripts for three distinct alpha chains of the type XI collagen molecule (alpha1(XI), alpha2(XI) and alpha3[XI]) undergo tissue-specific alternative splicing during the process of osteochondrogenesis. In the present study, we analyzed the splicing patterns of type XI collagen genes in osteochondrogenic tumors as well as in various normal tissues using the reverse transcription-polymerase chain reaction method. Analysis of normal subjects revealed the coordinated expression of short alpha1(XI), alpha2(XI) and alpha3(XI) transcripts in the normal differentiated cartilage. Osteochondroma followed this pattern, reflecting the highly chondrogenic phenotype of this benign tumor. Another benign tumor, chondroblastoma, exclusively expressed the long alpha1(XI) transcript, probably reflecting the lack of a chondrogenic nature. Among malignant chondrogenic tumors, the splicing patterns of type XI collagen transcripts were more complex, showing dissociated expression of long alpha1(XI) and short alpha2(XI) mRNAs. This expression pattern may reflect heterogeneous cell populations and may also reflect various levels of cell differentiation in malignant tumors. In addition, short alpha3(XI) expression switched to the long transcript as chondrosarcomas became more aggressive. Thus, the alternative splicing of type XI collagen genes seems to be oncodevelopmentally regulated and splicing analysis may therefore be a useful marker for chondrogenic tumors.

Alternative Splicing↗

Effects of various factors including the CYP2D6 genotype and coadministration of flunitrazepam on the steady-state plasma concentrations of bromperidol and its reduced metabolite.

The effects of various factors, including the cytochrome P450 (CYP) 2D6 genotype and the coadministration of flunitrazepam, on the steady-state plasma concentrations (Css) of bromperidol and its reduced metabolite were studied in 62 schizophrenic inpatients receiving bromperidol 12 mg/day. By use of allele-specific PCR analysis, the wild type allele (CYP2D6*1A) and four mutated alleles causing either absent (CYP2D6*3, CYP2D6*4 and CYP2D6*5) or decreased (CYP2D6*10) CYP2D6 activity were identified. The means (ranges) of the Css of bromperidol and reduced bromperidol corrected to the median body weight were 7.2 (1.3-17.4) and 2.2 (0.4-8.9) ng/ml, respectively. Neither the Css of bromperidol nor that of reduced bromperidol significantly differed among the patients with no (n = 28), one (n = 30) and two mutated alleles (n = 4). The patients coadministered with flunitrazepam (n = 52) had significantly (P < 0.05) higher Css of bromperidol, but not reduced bromperidol, than those not (n = 10). Age, sex and smoking had no significant effects on the Css of these compounds. The present study thus suggests that the polymorphic CYP2D6 is not involved in the metabolism of bromperidol and reduced bromperidol to a major extent. The coadministration of flunitrazepam inhibits the metabolism of bromperidol, but age, sex and smoking do not affect it.

Adolescent↗

Effect of itraconazole on the single oral dose pharmacokinetics and pharmacodynamics of alprazolam.

To assess the effect of itraconazole, a potent inhibitor of cytochrome P450 (CYP) 3A4, on the single oral dose pharmacokinetics and pharmacodynamics of alprazolam, the study was conducted in a double-blind randomized crossover manner with two phases of treatment with itraconazole-placebo or placebo-itraconazole. Ten healthy male subjects receiving itraconazole 200 mg/day or matched placebo orally for 6 days took an oral 0.8 mg dose of alprazolam on day 4 of each treatment phase. Plasma concentration of alprazolam was measured up to 48 h after alprazolam dosing, together with the assessment of psychomotor function by the Digit Symbol Substitution Test, Visual Analog Scale and Udvalg for kliniske undersøgelser side effect rating scale. Itraconazole significantly (P < 0.01) increased the area under the concentration-time curves from 0 h to infinity (252 +/- 47 versus 671 +/- 205 ng h/ml), decreased the apparent oral clearance (0.89 +/- 0.21 versus 0.35+/-0.10 ml/min per kg) and prolonged the elimination half-life (15.7 +/- 4.1 versus 40.3 +/- 13.5 h) of alprazolam. The test performed during itraconazole treatment showed significantly depressed psychomotor function. It is suggested that itraconazole, a potent CYP3A4 inhibitor, increases plasma concentration of alprazolam via its inhibitory effects on alprazolam metabolism. Thus, this study supports previous studies suggesting that CYP3A4 is the major enzyme catalyzing the metabolism of alprazolam. Enhanced side effects of alprazolam by itraconazole coadministration were probably reflected by these pharmacokinetic changes.

Administration, Oral↗

Correlation between steady-state plasma concentrations of mianserin and trazodone in depressed patients.

OBJECTIVE: The correlations between steady-state plasma concentrations of mianserin and its active metabolite desmethylmianserin and those of trazodone and its active metabolite m-chlorophenylpiperazine (m-CPP) were examined in 19 depressed patients. METHODS: Ten patients received first mianserin (30 mg per day) and second trazodone (150 mg per day), while 9 patients received these treatments in the opposite sequence, with at least 2-week intervals between the two phases. Blood was sampled at steady state, 1-3 weeks after initiation of each treatment. Plasma concentrations of mianserin, the separate enantiomers S(+)- and R(-)-mianserin, desmethylmianserin, trazodone and m-CPP were measured by means of high-performance liquid chromatography. RESULTS: There was a significant correlation between steady-state plasma concentrations of trazodone and total mianserin (r = 0.59) or S(+)-mianserin (r = 0.57), but not R(-)-mianserin (r = 0.33). CONCLUSION: The present study thus suggests that the metabolic capacity of mianserin, especially the more active S(+)-enantiomer, and that of trazodone correlate to each other. This finding supports the previous suggestions that cytochrome P4502D6 is involved in the metabolism of mianserin and trazodone.

Antidepressive Agents, Second-Generation↗

Florid periosteal reaction and focal fibrocartilaginous dysplasia.

Focal fibrocartilaginous dysplasia (FFCD) is a rare condition causing tibia vara in childhood. It is characterized by progressive tibia vara in young children with a characteristic radiographic lesion. This paper is thought to be the first to describe FFCD exhibiting florid periosteal reaction at the time of presentation with a subtle faint osteolytic lesion in the diametaphysis of the proximal tibia.

Bone Diseases, Developmental↗

Differential in situ expression of alpha2(XI) collagen mRNA isoforms in the developing mouse.

Type XI collagen is an essential structural component of the extracellular matrix of cartilage and plays a role in collagen fibril formation and skeletal morphogenesis. The expression of all three type XI collagen genes is not restricted to cartilage. In addition, alternative exon usage seems to increase the structural diversity and functional potential of type XI collagen during development. In order to investigate type XI collagen expression during development, we have examined alpha2(XI) and alpha1(XI) collagen genes by in situ hybridization in mice. Transcripts of the alpha2(XI) collagen gene were first detected in the notochord of mouse embryos after 11.5 days of gestation. Subsequently, alpha2(XI) mRNA was mainly found in the cartilaginous tissues of the developing limbs and axial skeleton together with transcripts of the alpha1(XI) gene. The alpha2(XI) transcripts seemed to be alternatively spliced isoforms lacking exons 6-8, which code for an acidic domain. Expression of alpha2(XI) outside the cartilage was relatively restricted, whereas expression of the alpha1(XI) gene was widespread. However, expression of alpha2(XI) transcripts containing exons 6-8 was found in non-chondrogenic tissues, including the calvarium and periosteum where intramembranous ossification occurs. These results indicate that alpha2(XI) mRNA isoforms are differentially expressed in various tissues during development. In addition, alpha2(XI) mRNA isoforms containing alternative exons are present in osteogenic cells, and their expression may be closely related to the formation of bone or cartilage.

Alternative Splicing↗

Intrameatal tumours presenting as a hearing disturbance: case reports of meningioma and lymphoma.

This paper presents two patients with chronic progressive hearing disturbance. Each patients had an intrameatal tumour, part of which extended to the cerebellopontine (CP) angle. In both cases, the patients were initially diagnosed with an acoustic neurinoma. A 63-year-old male experienced a hearing disturbance in the left ear for 1.5 years prior to visiting our hospital. Magnetic resonance (MR) imaging revealed a mass which was surgically resected. The tumour originated from the intrameatal dura mater. Histologically, the tumour was a meningioma. Similarly, a 53-year-old male presented with systemic lymphoma diagnosed 10 months earlier, and a hearing disturbance in the right ear that began 3 months prior to visiting our hospital. MR imaging prior to chemotherapy revealed a mass which extended to the CP angle. Part of the tumour in the CP angle disappeared after chemotherapy, suggesting a secondary lymphoma. Another tumour appeared later in Meckel's cave on the left side; however, it decreased in size following repeated chemotherapy. The present results indicate that differential diagnosis of intrameatal tumours and acoustic neurinomas may be difficult due to the small tumour size. Recent progress in neuroradiology may allow distinction of intrameatal tumours as a separate tumour classification. Our second patient is the sixth reported case of a CP angle lymphoma in the literature.

Diagnosis, Differential↗

Switch of osteonectin and osteopontin mRNA expression in the process of cartilage-to-bone transition during fracture repair.

The process of cartilage-to-bone transition (CBT) is a key event for the achievement of rigid bone healing during fracture repair. Since mineralization of cartilaginous matrix is a prerequisite for the initiation of CBT, the genetic localization of mineralization-related bone matrix proteins in CBT was examined in this study. An in situ hybridization method used on decalcified sections with digoxigenin-11-UTP labelled probes identified the cellular localizations of these genes in CBT. Cessation of osteonectin mRNA together with induction of osteopontin mRNA in chondrocyte maturation was observed during the process of CBT in the fracture callus on day 12 after fracture; osteocalcin mRNA was absent in chondrocytes of the CBT area. Induction of osteopontin mRNA in maturated chondrocytes was followed by the expression of mRNAs for osteonectin, osteopontin and osteocalcin in osteogenic cells in the ossification front of CBT. The data suggest that the switch from osteonectin to osteopontin mRNA expression in chondrocyte maturation is one of the key events during CBT. Transcriptional disorders of the expression of these molecules may be linked to the failure of fracture repair, i.e. delayed or prevented hypertrophic osteosynthesis.

Animals↗

Correlation between steady-state plasma concentrations (Css) of bromperidol and haloperidol.

1. Bromperidol is a close structural analogue of haloperidol, and its metabolic pathways are similar to those of haloperidol. The authors studied the correlation between the Css of bromperidol and haloperidol. 2. The subjects were 16 schizophrenic inpatients. Fourteen patients received firstly bromperidol 12 mg/day and secondly haloperidol 12 mg/day, while the remaining two patients received the two treatments in the opposite sequence. 3. Blood samplings were performed 2-3 weeks after the initiation of each treatment, and the Css of bromperidol, haloperidol and their reduced metabolites were measured by high-performance liquid chromatography. 4. Neither the correlation between the Css of bromperidol and haloperidol (r = 0.246) nor that between the Css of reduced bromperidol and reduced haloperidol (r = 0.142) was significant. 5. The present study thus suggests that the Css of bromperidol and haloperidol do not correlate well in individuals.

Adult↗

Effect of carbamazepine on the single oral dose pharmacokinetics of alprazolam.

The effect of carbamazepine, an inducer of cytochrome P450 (CYP) 3A4, on the single oral dose pharmacokinetics of alprazolam was examined in a double-blind, randomized crossover study with two phases. Seven healthy male subjects took carbamazepine 300 mg/day or matched placebo orally for 10 days, and on the 8th day they took a single oral 0.8 mg dose of alprazolam. Blood samples were taken and psychomotor function was assessed by the Digit Symbol Substitution Test, Visual Analog Scale, and UKU Side Effect Rating Scale up to 48 h after alprazolam dosing. Carbamazepine significantly (p < .01 to .001) decreased the plasma alprazolam concentrations during the elimination phase. Carbamazepine significantly (p < .001) increased the apparent oral clearance (0.90 +/- 0.21 vs. 2.13 +/- 0.54 ml/min/kg) and shortened the elimination half-life (17.1 +/- 4.9 vs. 7.7 +/- 1.7 h), with no significant effect on the peak plasma concentration (11.7 +/- 1.5 vs. 13.0 +/- 3.5 ng/ml). The majority of psychomotor function parameters during the carbamazepine treatment were not significantly different from those during the placebo treatment, probably because of the sedative effect of carbamazepine itself. The present study suggests that carbamazepine decreases plasma concentration of alprazolam by inducing its metabolism. It also supports the previous studies, suggesting that alprazolam is metabolized predominantly by CYP3A4.

Adult↗