Biomedical subjects

K Otani

Publications and source records attributed to K Otani.

At least 91 records · Page 5Linked to original sources

PubMed1997

Experimental disc herniation: evaluation of the natural course.

STUDY DESIGN: Changes in L7 nerve root conduction velocity and changes in appearance on magnetic resonance study of the L6-L7 intervertebral disc in the dog were assessed for 2-6 months after an experimental disc herniation was performed. OBJECTIVES: To assess the time-related changes of nerve conduction velocity and magnetic resonance changes of the intervertebral discs. SUMMARY OF BACKGROUND DATA: It is known that nucleus pulposus may induce nerve root morphologic and functional changes when applied epidurally. However, it is not known whether such changes are reversible. METHODS: The spinal canal was opened by laminotomy of the upper part of the L7 lamina and the lower part of the L6 lamina on the left side. The L7 nerve root was gently retracted (sham) or the disc was punctured and injected with saline to produce herniation of the nucleus pulposus during the retraction time (herniation). After 1 day to 2 months, nerve root conduction velocity was determined by local electrical stimulation. Six dogs had the herniation or the sham procedure, and the L6-L7 disc was studied by magnetic resonance imaging at various times up to 6 months after the procedure. RESULTS: Decrease in nerve conduction velocity reached a maximum after 7 days and recovered to baseline level fully within 2 months. Although there was a clear reduction-recovery pattern, the difference in conduction velocity compared with that of the sham group was statistically significant after only 7 days. Disc degeneration started in the herniated discs within 7 days after the herniation procedure. However, none of the experimentally induced disc herniations were visualized by magnetic resonance imaging 7 days after the procedure. In no case was there subsequent nerve root compression. In one case, disc protrusion was visible 6 months after the herniation procedure. CONCLUSIONS: The results demonstrate for the first time that nucleus pulposus-induced nerve root injury reverses in 2 months and that it may be present without simultaneous nerve root compression, as confirmed by findings in magnetic resonance imaging. The previously described nucleus pulposus-induced nerve root changes may therefore be of clinical importance, and experimental studies of these mechanisms will probably be relevant for expanded understanding of the pathophysiologic mechanism behind sciatica that is caused by disc herniation.

Animals↗

PubMed1997

Relationship between the CYP2D6 genotype and the steady-state plasma concentrations of trazodone and its active metabolite m-chlorophenylpiperazine.

The relationship between the cytochrome P450 (CYP) 2D6 genotype and the steady-state plasma concentrations (Css) of trazodone and its active metabolite m-chlorophenylpiperazine (mCPP) was studied in 54 depressed Japanese patients receiving trazodone 150 mg at bedtime. By use of allele-specific PCR analysis, the wild type allele, three mutated alleles causing absent enzyme activity (CYP2D6A, CYP2D6B and CYP2D6D) and one mutated allele causing decreased enzyme activity (CYPZD6 Ch) were identified. The means (ranges) of the Css of trazodone, corrected to the median body weight in 17 cases with no mutated allele, 27 cases with one mutated allele and 10 cases with two mutated alleles, were 556 (281-1115), 643 (302-1362) and 671 (234-1418) ng/ml, respectively, while the values of mCPP were 60 (35-121), 65 (33-99) and 58 (38-112) ng/ml, respectively. Neither the Css of trazodone (F = 0.80, P = 0.45) nor that of mCPP (F = 0.49, P = 0.61) significantly differed among the three groups. The present study thus suggests that the CYP2D6 genotype cannot predict the Css of these compounds.

Adult↗

PubMed1997

Interaction between carbamazepine and bromperidol.

OBJECTIVE: The interaction between carbamazepine and bromperidol was studied in 13 schizophrenic inpatients. METHODS: Before carbamazepine addition, the subjects were taking bromperidol 12-24 mg.day-1 for 1-20 weeks. Carbamazepine 400 mg.day-1 was coadministered for 4 weeks, and blood samplings were performed before carbamazepine addition and at weekly intervals after the addition. Plasma concentrations of bromperidol and its reduced metabolite were measured by high-performance liquid chromatography. RESULTS: Carbamazepine significantly decreased plasma concentrations of both bromperidol and reduced bromperidol for all weeks. On average, the plasma concentrations of bromperidol and reduced bromperidol at 4 weeks were 37% and 23% of the corresponding precarbamazepine values. Despite these decreases in plasma concentration, the Clinical Global Impression scores decreased slightly but significantly after carbamazepine addition. CONCLUSION: The present study suggests that carbamazepine decreases plasma concentrations of bromperidol and its reduced metabolite by inducing the metabolism of these compounds. Nevertheless, adjunctive carbamazepine may be useful for schizophrenic patients treated with bromperidol.

Adult↗

PubMed1997

Anterior instrumentation in idiopathic scoliosis: a minimum follow-up of 10 years.

One hundred and thirty-four patients with idiopathic scoliosis were treated between 1973 and 1993 in our hospital, and 53 were followed for a minimum of 10 years in a retrospective study. Forty-five were female and 8 male with an average age of 32 years at follow up. Dwyer instrumentation was used in 17 and Zielke in 36. The curve was thoracic in 16, thoracolumbar in 27 and lumbar in 10. The average preoperative Cobb angle was 64 degrees. The average angle at follow up was 21 degrees with 62% of the average correction maintained (61% in the Dwyer and 65% in the Zielke). Most patients were satisfied subjectively and we recommend this type of operation.

Activities of Daily Living↗

PubMed1997

Metabolic disposition of pantoprazole, a proton pump inhibitor, in relation to S-mephenytoin 4'-hydroxylation phenotype and genotype.

OBJECTIVES: To assess the possible relationship between the metabolic disposition of pantoprazole and genetically determined S-mephenytoin 4'-hydroxylation phenotype and genotype. METHODS: The pharmacokinetic disposition of pantoprazole was investigated in 14 Japanese male volunteers (seven extensive and seven poor metabolizers of S-mephenytoin). All subjects received a single 40 mg oral dose of pantoprazole as the enteric-coated formulation. RESULTS: An interphenotypic difference in the metabolic disposition of pantoprazole was observed: the mean values for area under the concentration-time curve (AUC), elimination half-life (t1/2), and apparent oral clearance were significantly (p < 0.01) greater, longer, and lower, respectively, in the poor metabolizers than in the extensive metabolizers. The mean AUC of pantoprazole sulfone was greater (p < 0.01) in the poor metabolizers than in the extensive metabolizers, whereas the mean AUC of the main demethylated metabolite (M2) was lower (p < 0.01) in the poor metabolizers than in the extensive metabolizers. A significant negative correlation was observed between the individual values for log10% urinary excretion of 4'-hydroxymephenytoin and AUC of pantoprazole (rs = -0.816; p < 0.005). The CYP2C19 genotyping test results were found to be in a complete accordance with the phenotypes. CONCLUSION: These data indicated that the metabolic disposition of pantoprazole is under the pharmacogenetic control of S-mephenytoin 4'-hydroxylase (CYP2C19).

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed1997

Cyclic tensile stretch on bovine articular chondrocytes inhibits protein kinase C activity.

Osteoarthrosis, a common pathway of joint deterioration, is caused by mechanical stress loaded on articular cartilage. We previously demonstrated the involvement of protein kinase C (PKC) in the development of osteoarthritis in vitro. In this study, we examined the effect of mechanical stress on chondrocyte metabolism and the activity of PKC in vitro. Low frequency and magnitude of cyclic tensile stretch loaded on chondrocytes increased proteoglycan synthesis. However, high frequency and magnitude of stress decreased its synthesis. In this condition, activity of PKC was reduced. These results suggest an involvement of PKC in the stress-mediated inhibition of proteoglycan synthesis.

Animals↗

PubMed1997

Plasma concentrations of trazodone and m-chlorophenylpiperazine at steady state can be predicted from those after an initial dose of trazodone.

1. The authors studied the correlations between plasma concentrations of trazodone and mCPP at steady state and those after an initial dose of trazodone. 2. Fifteen depressed patients received trazodone 150 mg at bedtime for 3 weeks, and blood samplings were taken 12 h after the initial dose and 12 h after the last dose at each week. Plasma concentrations of trazodone and mCPP were measured by high-performance liquid chromatography. 3. Plasma concentration of mCPP, but not trazodone, was significantly higher at each week than after initial dosing. 4. For both trazodone and mCPP, significant linear relationships were found between plasma concentration after initial dosing and the average of 3 weeks' plasma concentrations. 5. The present study thus suggests that plasma concentrations of trazodone and mCPP at steady state can be predicted from those after an initial dose of trazodone.

Adult↗

PubMed1997

Possible interaction between cisapride and bromperidol.

1. The case of a schizophrenic patient taking bromperidol (18 mg/day), whose psychotic symptoms deteriorated markedly after addition of cisapride (7.5 mg/day), is presented. 2. Retrospective determination of drug concentrations revealed that plasma concentrations of bromperidol and its reduced metabolite were increased after cisapride addition. 3. The present study thus suggests that there is an interaction between cisapride and bromperidol.

Adult↗

PubMed1997

Prognosis of infants with ankle clonus within the first year of life.

The present study was undertaken to clarify how we should assess the necessity of close follow-up in each case, when we first examine an infant with ankle clonus within the first year of life. The neurologic prognoses of 169 infants who had exhibited ankle clonus at least once during the first year of life were reviewed in relation to the age at examination for positive response, degree of response, and coexisting neurologic signs other than ankle clonus. Ninety-seven of them (57.4%) were normal, while the rest had diverse pathologic outcomes: cerebral palsy in 49, mental retardation in 12, borderline intelligence in 9, and motor delay in 2. The neurologic prognoses in infants whose ankle clonus was more than ten beats at any age within the first year of life, and ten or less beats over 8 months of age were always abnormal. In the subjects whose neurologic signs other than ankle clonus appeared within 4 months of age and persisted after 5 months of age, prognoses were generally poor. In infants with such findings, their clinical courses should be closely observed for the possible development of neurologic abnormalities.

Adolescent↗

PubMed1997

Effects of genetically determined S-mephenytoin 4-hydroxylation status and cigarette smoking on the single-dose pharmacokinetics of oral alprazolam.

This study examines the effects of genetically determined S-mephenytoin 4-hydroxylation capacity and cigarette smoking on the single-dose pharmacokinetics of oral alprazolam in 12 healthy male volunteers. Six subjects each were extensive metabolizers (EMs) and poor metabolizers (PMs) of S-mephenytoin 4-hydroxylation. Seven subjects were smokers (> 10 cigarettes/day), and five were nonsmokers, according to their self-reports. Each subject took a single oral dose of 0.8 mg of alprazolam, and blood samples were collected up to 48 hours postdose. Psychomotor function was assessed at times of blood samplings using the Digit Symbol Substitution Test (DSST), Visual Analog Scale (VAS), and UKU Side Effect Rating Scale. Plasma alprazolam concentrations were measured by a high-performance liquid chromatography assay. None of the mean pharmacokinetic parameters was significantly different between the EM and PM phenotype groups. Although the mean elimination half-life was significantly shorter in the smoker group (p < .01) than in the nonsmoker group (13.1 +/- 2.9 vs. 20.0 +/- 2.7 hours, mean +/- SD), other pharmacokinetic parameters did not differ significantly between the two groups. Psychomotor function parameters did not differ significantly either between the EM and PM groups or between the nonsmoker and smoker groups. The present study thus suggests that neither S-mephenytoin 4-hydroxylation status nor self-reports of extensive cigarette smoking has a major impact on the metabolism of alprazolam in humans.

Adult↗

PubMed1997

Observer agreement in the assessment of mandibular trabecular bone pattern from panoramic radiographs.

OBJECTIVES: To study the observer agreement in the assessment of trabecular pattern of the mandible from panoramic radiographs. METHODS: Seven observers were asked to classify the trabecular pattern of 100 edentulous regions of the mandible in 80 randomly selected panoramic radiographs into one of five grades with the aid of a written description and reference images. Intra- and interobserver agreement was calculated as overall agreement and Kappa index. RESULTS: The intra-observer agreement varied between 65% and 79%. The Kappa index for intra-observer agreement was moderate for three observers and substantial for four. For all seven observers, it varied according to the grade of trabecular bone pattern, but the majority deviated from each other by only one grade. CONCLUSION: The relatively high rates of observer agreement indicate that panoramic radiography can be used for the clinical assessment of the trabecular pattern of the mandible.

Adult↗

PubMed1997

The CYP2D6 genotype and plasma concentrations of mianserin enantiomers in relation to therapeutic response to mianserin in depressed Japanese patients.

The relationship between therapeutic response to racemic mianserin and steady-state plasma concentrations of S(+)- and R(-)-mianserin was studied in 26 Japanese patients with major depression. The daily dose of mianserin was 30 mg, and the duration of treatment was 3 weeks. Regarding S-mianserin, the proportion of responders (final Montgomery-Asberg Depression Rating Scale score of 10 or less) was significantly higher in the plasma concentration range of 10 to 23 ng/mL than outside (10 of 11 vs. 3 of 15, p = 0.0005). Such a plasma concentration difference between responders and nonresponders was not found for R-mianserin. In 15 patients, the relationships between the CYP2D6 genotype, determined by allele-specific polymerase chain reaction analysis and Escherichia coli RI restriction fragment length polymorphism, plasma concentrations of the enantiomers, and the therapeutic response were studied. Five patients were homozygous for the wild type (wt) allele (wt/wt), nine were heterozygous for the CYP2D6Ch (Ch) allele causing decreased CYP2D6 activity (Ch/wt), and one patient was heterozygous for the Ch allele and the defect allele CYP2D6D (D) (Ch/D). The Ch/wt group showed significantly higher plasma concentrations of S-mianserin (mean +/- SD: 15 +/- 6 vs. 8 +/- 1 ng/mL, p = 0.007) and proportion of responders (8 of 9 vs. 1 of 5, p = 0.023) than the wt/wt group. The patient with the Ch/D genotype had the highest plasma concentration of S-mianserin (37 ng/mL) and a poor response. No significant relationship was found between the CYP2D6 genotype and plasma concentration of R-mianserin. The study presented here thus suggests that the CYP2D6 genotype plays a major role in controlling plasma concentration of the S-enantiomer of mianserin, which contributes to a major extent to the antidepressant effect during mianserin treatment.

Adult↗

PubMed1997

Relationship between single oral dose pharmacokinetics of alprazolam and triazolam.

The relationship between the single oral dose pharmacokinetics of alprazolam and triazolam was studied in 10 healthy male volunteers. Each subject took single oral doses of alprazolam 0.8 mg and triazolam 0.5 mg with at least a 2 week interval between each dose. Blood samplings were performed up to 48 h after alprazolam dosing and up to 12 h after triazolam dosing. Plasma concentrations of both drugs were measured by high-performance liquid chromatography. The means +/- standard deviation of the peak plasma concentration, the total area under the plasma concentration-time curve and the elimination half-life of alprazolam were 11.3 +/- 3.1 ng/ml, 232.4 +/- 59.2 ng/h/ml and 16.5 +/- 4.6 h, respectively, and those of triazolam were 3.2 +/- 1.0 ng/ml, 11.8 +/- 5.2 ng/h/ml and 2.5 +/- 1.1 h, respectively. There was no significant correlation between the two drugs in any pharmacokinetic parameters (r = 0.35, 0.25 and 0.50). The present study thus suggests that the single oral dose pharmacokinetics of alprazolam and triazolam do not correlate well in individuals.

Adult↗

PubMed1997

Carbamazepine toxicity induced by clarithromycin coadministration in psychiatric patients.

Seven psychiatric inpatients receiving carbamazepine 600 mg/day were coadministered clarithromycin 400 mg/day for 5 days to treat atypical pneumonia. Blood samples were taken after clarithromycin coadministration and at 1 and 4 weeks after its discontinuation. Plasma concentrations of carbamazepine and carbamazepine-10,11-epoxide were measured using high-performance liquid chromatography. During clarithromycin coadministration, four out of the seven patients developed moderate-to-severe toxic symptoms of carbamazepine, such as drowsiness, dizziness, and ataxia, which resolved within 5 days after clarithromycin discontinuation. In these four patients, plasma carbamazepine concentrations after clarithromycin coadministration were approximately twice as high as those after its discontinuation. In the seven patients, the mean plasma concentration of carbamazepine, but not of carbamazepine-10,11-epoxide, after clarithromycin coadministration was significantly (p < 0.01) higher than those at 1 and 4 weeks after its discontinuation. The present report suggests that clarithromycin coadministration induces increased plasma carbamazepine concentrations, which may result in carbamazepine toxicity. Therefore, care should be given to prescribing clarithromycin for patients receiving carbamazepine.

Aged↗

PubMed1997

Reduction malarplasty.

One of the most frequently requested facial contour improvement procedures in the Orient is reduction malarplasty. However, until recently, osteotomies in the malar region have been performed by means of a coronal incision that required a larger incision and more invasive procedure than many patients are comfortable with when considering an elective cosmetic surgical procedure. We have developed a reduction malarplasty method to improve facial contours that circumvents the drawbacks inherent in the conventional method. In our method, the protrusion in the cheekbone area is corrected by performing an osteotomy of the zygoma through an intraoral incision and an osteotomy of the zygomatic arch through a small preauricular incision.

Adult↗

PubMed1997

Increases in plasma concentration of m-chlorophenylpiperazine, but not trazodone, with low-dose haloperidol.

Our previous study suggested that cytochrome P4502D6 (CYP2D6) is involved in the metabolism of trazodone and its active metabolite, m-chlorophenylpiperazine (m-CPP). The purpose of this study was to examine the degrees of increase in plasma concentrations of trazodone and m-CPP induced by haloperidol, which is an inhibitor of CYP2D6. The subjects were nine depressed inpatients receiving trazodone at bedtime (150 mg in seven patients and 300 mg in two) for 2-19 weeks. Haloperidol at 4 mg/day was coadministered for 1 week, and blood samplings were taken before and after the coadministration. Contrary to our expectation, haloperidol did not significantly increase the mean plasma trazodone concentration (810 +/- 382 vs. 856 +/- 357 ng/ml). However, haloperidol significantly increased (p < 0.01) the mean plasma m-CPP concentration (78 +/- 31 vs. 92 +/- 34 ng/ml).

Adult↗

PubMed1997

No effect of the anticholinergic drugs trihexyphenidyl and biperiden on the plasma concentrations of bromperidol and its reduced metabolite.

Effects of the anticholinergic drugs trihexyphenidyl and biperiden on plasma concentrations of bromperidol and its reduced metabolite were studied. Subjects comprised 20 schizophrenic inpatients taking bromperidol, 6-18 mg/ day for 1-9 weeks. Patients were randomly allocated to one of two treatment sequences: trihexyphenidyl-biperiden (n = 12) or biperiden-trihexyphenidyl (n = 8). Each sequence consisted of two 2-week phases, with no washout period between the two phases. The daily dose of trihexyphenidyl was 8 mg and that of biperiden 6 mg. Plasma concentrations of bromperidol and reduced bromperidol were measured using high-performance liquid chromatography (HPLC). There was no significant difference in plasma bromperidol or reduced bromperidol concentrations among baseline, trihexyphenidyl and biperiden phases: 7.3 +/- 3.7 versus 7.2 +/- 4.1 versus 7.0 +/- 4.3 ng/ml and 2.0 +/- 2.1 versus 2.2 +/- 2.1 versus 1.9 +/- 2.0 ng/ml, respectively. The present study thus suggests that neither trihexyphenidyl nor biperiden affects plasma concentrations of bromperidol and its reduced metabolite.

Adult↗

PubMed1997

Increased plasma concentrations of bromperidol and its reduced metabolite with levomepromazine, but not with thioridazine.

Bromperidol is a close structural analog of haloperidol. The authors studied the effects of levomepromazine and thioridazine, which are frequently added to other neuroleptics as sedatives, on plasma concentrations of bromperidol and its reduced metabolite. The subjects were 26 inpatients with schizophrenia receiving bromperidol, 12 to 24 mg/day, for 1 to 19 weeks. In 10 cases, 50 mg levomepromazine per day and in nine cases, 50 mg thioridazine per day were coadministered for 1 week. In seven cases, both drugs were coadministered with > or = 2-week intervals. Plasma concentrations of bromperidol and reduced bromperidol were measured by a high-performance liquid chromatographic method. Levomepromazine (n = 17) significantly (p < 0.001) increased plasma concentrations of bromperidol (7.3 +/- 4.1 versus 10.2 +/- 4.8 ng/ml) and reduced bromperidol (1.8 +/- 1.4 versus 4.5 +/- 3.3 ng/ml). Thioridazine (n = 16) did not significantly change plasma concentrations of bromperidol (9.1 +/- 5.7 versus 8.6 +/- 5.5 ng/ml), while those of reduced bromperidol could not be measured because of interfering peaks. The current study suggests that levomepromazine, but not thioridazine, increases plasma concentrations of bromperidol and reduced bromperidol by inhibiting the metabolism of these compounds.

Adult↗