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Biomedical subjects

K Otani

Publications and source records attributed to K Otani.

At least 19 recordsLinked to original sources
PubMed2002

Nucleus pulposus-induced nerve root injury: effects of diclofenac and ketoprofen.

MAIN PROBLEM: Nucleus pulposus and/or chronic compression can induce spinal nerve root injury. Inflammation has been proposed as having major importance in the pathophysiologic mechanisms involved in the induction of such injuries. Corticosteroids, potent anti-inflammatory drugs, have been demonstrated to reduce nucleus pulposus-induced spinal nerve root injury. The aim of the present study was to assess the effects of two potent non-steroidal anti-inflammatory drugs (NSAIDs), diclofenac and ketoprofen, in experimental nucleus pulposus-induced spinal nerve root injury in a pig model. METHODS: Eighteen pigs were included in the study. Autologous nucleus pulposus was harvested from a lumbar disc and applied locally around the first sacral nerve root after a partial laminectomy of the first and second sacral vertebrae. Six pigs were treated with daily intramuscular injections of diclofenac, 3 mg/kg body weight, for 7 days. Six other pigs were treated with daily intramuscular injections of ketoprofen, 4 mg/kg body weight, for 7 days. As controls, six pigs received injections with physiologic saline. After 7 days, the pigs were reanesthetized and the nerve conduction velocity over the exposed nerve root area was determined. RESULTS: The nerve conduction velocity was significantly higher in pigs treated with diclofenac than in the saline-treated controls, (57 +/- 6 m/s vs 38 +/- 18 m/s, P<0.05, Student's t-test). The velocity in pigs treated with ketoprofen, 42 +/- 24 m/s, did not differ significantly from that of controls. CONCLUSIONS: This study of two potent NSAIDs indicates that nucleus pulposus-induced nerve root dysfunction may be reduced by diclofenac but not by ketoprofen. The reason for this difference is not known, but it might be related to the fact that ketoprofen and diclofenac belong to different NSAID subgroups and have a different selectivity for the two cyclo-oxygenases COX-1 and COX-2.

Animals↗
PubMed2001

Effects of diclofenac and ketoprofen on nerve conduction velocity in experimental nerve root compression.

STUDY DESIGN: The effects of diclofenac and ketoprofen on nerve conduction velocity in experimental nerve root compression were evaluated in a setup using an established pig model. OBJECTIVE: To assess the effects of two potent nonsteroidal antiinflammatory drugs, diclofenac and ketoprofen, in experimental nerve root compression. SUMMARY OF BACKGROUND DATA: Compression of spinal nerve roots is recognized to be of major etiologic importance for several common spinal pain syndromes. Secondary inflammatory changes, induced by microvascular permeability changes and leakage of inflammatory mediators into the endoneural tissue, have been proposed as important for the induction of spinal nerve root injury by chronic compression. METHODS: This study involved 21 pigs. An ameroid constrictor was used to induce compression. Seven pigs were treated with daily intramuscular injections of diclofenac 3 mg/kg for 7 days. Seven other pigs were treated with daily intramuscular injections of ketoprofen 4 mg/kg. For a control, seven pigs did not receive any drug treatment. After 7 days, the pigs were reanesthetized, and the nerve conduction velocity in the compressed nerve root segments was determined. RESULTS: The nerve conduction velocity was significantly higher (P < 0.05, Student's t test) in the pigs treated with diclofenac (50 +/- 16 m/second) than in the untreated pigs (32 +/- 15 m/second). The nerve conduction velocity also was significantly higher (P < 0.05) in the pigs treated with ketoprofen (59 +/- 16 m/second) than in the untreated pigs. There were no significant differences in nerve conduction velocity between pigs treated with ketoprofen and those treated with diclofenac. CONCLUSIONS: The findings indicate that intramuscular administration of diclofenac or ketoprofen, both potent antiinflammatory drugs, may reduce nerve root dysfunction induced by compression of spinal nerve roots in an experimental pig model.

Animals↗
PubMed2001

Relationship between Taq1 A dopamine D2 receptor (DRD2) polymorphism and prolactin response to bromperidol.

The dopamine D2 receptor (DRD2) gene has a Taq1 A restriction fragment length polymorphism yielding two alleles, A1 and A2. We have previously shown that female patients with the A1 allele show greater prolactin response to nemonapride, a selective antagonist for D2-like dopamine receptors, in schizophrenic patients. In the present study, the relationship between this polymorphism and prolactin response to bromperidol was investigated in 32 untreated schizophrenic inpatients (16 males, 16 females). The daily dose of bromperidol was fixed at 6 (n = 10), 12 (n = 13), or 18 mg (n = 9) during a 2-week treatment period. Taq1 A genotypes were determined by PCR method. Plasma prolactin concentration was measured by radioimmunoassay. Plasma concentration of bromperidol was measured by HPLC method. The subjects were divided into four subgroups by gender and the genotypes, i.e., 10 males and 11 females with the A1 allele, 6 males and 5 females with no A1 allele. The females with the A1 allele had the highest Delta prolactin (the change from the pretreatment concentration)/bromperidol concentration ratio among the other groups (P < 0.05). The present study thus suggests that female patients with the A1 allele show greater prolactin response to bromperidol, who may have a high risk for adverse effects associated with neuroleptic-induced hyperprolactinemia.

Adult↗
PubMed2001

No relationship between--141C Ins/Del polymorphism in the promoter region of dopamine D2 receptor and extrapyramidal adverse effects of selective dopamine D2 antagonists in schizophrenic patients: a preliminary study.

Previous studies have shown that subjects without Del alleles of the--141C Ins/Del polymorphism in the promoter region of the dopamine D2 receptor (DRD2) gene have lower DRD2 density that those with one or two Del alleles. The present study aims to investigate the relationship between the -141C Ins/Del polymorphism and extrapyramidal adverse effects of bromperidol and nemonapride, antipsychotic drugs with a selective and potent DRD2 antagonistic property, in schizophrenic inpatients. Twenty-seven patients were treated with bromperidol at a fixed-dose of 6, 12 or 18 mg/day, and 25 patients were treated with nemonapride at a fixed-dose of 18 mg/day. The duration of treatment with these drugs was 3 weeks. The Ins and Del alleles were determined by PCR. Extrapyramidal adverse effects were assessed by the Udvalg for Kliniske Undersøgelser side effects rating scale. The subjects consisted of 38 homozygotes of the Ins allele and 14 heterozygotes of the Ins and Del alleles. There were no significant differences in the incidence or severity of extrapyramidal adverse effects between patients with and without the Del allele. It is possible that this result was due to a lack of statistical power. However, the present study suggests that the--141C Ins/Del polymorphism is not related to the development of extrapyramidal adverse effects during acute-phase treatment with antidopaminergic agents.

Adult↗
PubMed2001

Increased urinary excretion of bilirubin oxidative metabolites in septic patients: a new marker for oxidative stress in vivo.

BACKGROUND: Bilirubin oxidative metabolites (BOMs) are generated from bilirubin as a result of its scavenging action against free radicals. During sepsis, excess amounts of free radicals are produced, and they play an important role in the pathophysiological process. We studied whether urinary excretion of BOMs would increase under septic conditions in humans and compared BOM levels with other well-established clinical parameters of inflammation. METHODS: In 19 septic patients and 28 nonseptic control patients, the BOM concentrations in urine were measured by enzyme-linked immunosorbent assay with an anti-bilirubin antibody. RESULTS: Urinary BOM levels in septic patients were much higher than those in control patients (21.6 +/- 2.5 vs 1.4 +/- 0.4 micromol/g creatinine, P < 0.001). Although there was a linear correlation between urinary BOM and serum total bilirubin levels (r = 0.392, P = 0.008), serum bilirubin levels were not significantly higher in the septic group than in the control group (P = 0.072). BOM levels correlated with body temperature (r = 0.801, P < 0.001), white blood cell counts in the peripheral blood (r = 0.590, P < 0.001), serum C-reactive protein (r = 0.653, P < 0.001), and the acute physiological and chronic health evaluation (APACHE II) score (r = 0.467, P = 0.003). CONCLUSIONS: These results demonstrated a urinary increase in BOMs in septic patients. This increase indicates that urinary BOM level is a possible marker for continuous monitoring of sepsis severity in clinical practice.

APACHE↗
PubMed2001

No correlations between the urinary ratio of 6beta-hydroxycortisol to free cortisol and pharmacokinetics of alprazolam.

OBJECTIVE: The urinary ratio of 6beta-hydroxycortisol to cortisol is known as a possible marker of CYP3A4 activity. We investigated the correlation between this ratio and the disposition of alprazolam, which is a substrate of CYP3A4. METHODS: Twelve healthy volunteers took a single dose (0.8 mg) of alprazolam at 0800 hours. Blood samplings were conducted up to 48 h after the dosing. Urine was collected during the 24 h prior to dosing. Quantification of alprazolam in plasma and that of cortisol and 6beta-hydroxycortisol in urine was performed using high-performance liquid chromatography. RESULTS: Mean (+/-SD) values of peak plasma concentration (Cmax), time to Cmax (tmax), area under the plasma concentration-time curve [AUC(0-48)] and elimination half-life (tl/2) of alprazolam were 12.0+/-3.0 ng/ml, 1.5+/-0.9 h, 200+/-41 ng/ml h and 16.0+/-4.3 h, respectively. Mean (+/-SD) urinary ratio of 6beta-hydroxycortisol to cortisol was 3.28+/-0.67. No significant correlations were found between urinary ratio of 6beta-hydroxycortisol to cortisol and any pharmacokinetic parameters of alprazolam (Cmax: rs= -0.06; tmax: r(s)= 0.34; AUC(0-48): rs=0.08; t1/2: r(s)= -0.36). CONCLUSION: This study suggests that the urinary ratio of 6beta-hydroxycortisol to cortisol is unlikely to predict pharmacokinetics of alprazolam.

Adult↗
PubMed2001

Association between TaqI A dopamine D2 receptor polymorphism and therapeutic response to bromperidol: a preliminary report.

The relationship between TaqI A dopamine D2 receptor (DRD2) polymorphism and therapeutic response to bromperidol, a selective dopamine antagonist, was investigated in 30 acutely exacerbated schizophrenic inpatients. Patients were treated with bromperidol 6-18 mg/day for 3 weeks. Clinical symptoms were evaluated by the Brief Psychiatric Rating Scale (BPRS) before and 3 weeks after the treatment. The TaqI A genotypes were determined with the PCR method. There was no significant difference in the percentage improvement of total BPRS or 5-subgrouped symptoms (positive, negative, anxiety-depression, excitement and cognitive symptoms) after the 3-week treatment between the patients with A1 alleles (n=18) and those with no A1 allele (n=12). Although the present study is preliminary, it is suggested that the TaqI A DRD2 polymorphism is not associated with therapeutic response to bromperidol in schizophrenic patients.

Adult↗
PubMed2001

Nucleotide sequence analysis of the binding site on the inositol 1,4,5-trisphosphate type-1 receptor in bipolar disorder -- a negative study.

Pharmacological studies of bipolar disorder suggest that dysfunction of calcium mobilization via phosphatidylinositol-mediated transduction may be involved in its pathogenesis. The present study tests the hypothesis that dysfunction of calcium mobilization in bipolar disorder is due to the mutation of the nucleotide sequence in the FKBP12 binding site on the inositol 1,4,5-trisphosphate type-1 receptor (IP(3)R1). Nucleotide sequence analysis of the FKBP12 binding site on IP(3)R1 was performed using reverse transcription-polymerase chain reaction and DNA sequencing. The nucleotide sequence in this region was preserved in all subjects. This finding suggests that IP(3)R1 dysfunction through the FKBP12 binding site is not involved in the pathogenesis of bipolar disorder.

Adult↗
PubMed2001

A successful clonazepam treatment without tolerance in a patient with spontaneous oral dyskinesia.

There has been few reports on the effective treatment for SOD, which is phenomenologically similar to TD. A 66-year-old female with SOD was successfully treated by CNZ 2 mg/day. Even after one year of continuous treatment, tolerance, which is the major problem in the CNZ treatment for TD, did not develop. This report suggests that CNZ is effective at least for some patients with SOD.

Aged↗
PubMed2001

Dose-dependent augmentation effect of bromocriptine in a case with refractory depression.

1. A 52-year-old female with refractory depression had not responded to various treatments including electroconvulsive therapy and augmentation therapy with lithium or triiodothyronine. 2. Addition of bromocriptine 2.5-5 mg/day to imipramine improved her depressive symptoms. However, when the dose was increased to 15 mg/day to treat residual depressive symptoms, her clinical status deteriorated and returned to the original level. The dose reduction to 5mg/day again improved her depressive symptoms. 3. This report confirms the augmentation effect of bromocriptine for refractory depression. It also suggests that there is dose-dependency in this effect.

Bromocriptine↗
PubMed2001

Effects of genetic polymorphism of CYP1A2 inducibility on the steady-state plasma concentrations of trazodone and its active metabolite m-chlorophenylpiperazine in depressed Japanese patients.

The effects of a genetic polymorphism of inducibility of cytochrome P450 (CYP) 1A2 on the steady-state plasma concentrations of trazodone and its active metabolite, m-chlorophenylpiperazine, were studied in order to clarify if these steady-state plasma concentrations are dependent on the CYP1A2 polymorphism. Fifty-eight Japanese depressed patients received trazodone 150 mg/day at bedtime. The steady-state plasma concentrations of trazodone and m-chlorophenylpiperazine were measured in duplicate using high performance liquid chromatographic method, and were corrected to the mean body weight for analyses. A point mutation from guanine (wild type) to adenine (mutated type) at position -2964 in the 5'-flanking region of CYP1A2 gene was identified by polymerase chain reaction fragment length polymorphism method. The mean steady-state plasma concentration of trazodone, but not m-chlorophenylpiperazine was significantly (P<0.05) lower in smokers than in non-smokers. Twenty-two smokers had 16 homozygotes of the wild type allele, 5 heterozygotes of the wild type and mutated alleles, and one homozygote of the mutated allele. There was no significant difference in the mean steady-state plasma concentration of trazodone or m-chlorophenylpiperazine between smokers with no mutation and those with mutation, although one homozygote of the mutated allele had the highest steady-state plasma concentration of trazodone in smokers. The present study thus suggests that CYP1A2 polymorphism does not necessarily have predictive value of the steady-state plasma concentration of trazodone or m-chlorophenylpiperazine in most of the smokers treated with trazodone.

Adult↗
PubMed2001

Stereoselective pharmacokinetics of pantoprazole, a proton pump inhibitor, in extensive and poor metabolizers of S-mephenytoin.

Pantoprazole, a proton pump inhibitor, is administered as a racemic mixture. To determine the role of cytochrome P450 (CYP) 2C19 in the stereoselective metabolism of pantoprazole, we investigated the pharmacokinetic disposition of (+)- and (-)-pantoprazole in 7 extensive metabolizers and 7 poor metabolizers of S-mephenytoin. All of the subjects received an oral 40-mg dose of racemic pantoprazole as the enteric-coated formulation. In the extensive metabolizers, the mean clearance of (-)-pantoprazole was only slightly lower than that of (+)-pantoprazole and no significant differences in the other pharmacokinetic parameters between (+)- and (-)-pantoprazole were observed. The mean (+)/(-) ratios for maximum concentration, area under the plasma concentration-time curve from 0 to infinity, and elimination half-life were 0.94, 0.82, and 0.90, respectively. In contrast, in the poor metabolizers, the clearance values of both enantiomers were significantly lower than those in the extensive metabolizers, and a significant difference in pharmacokinetics between (+)- and (-)-pantoprazole was observed. The mean elimination half-life for (+)-pantoprazole was 3.55-fold longer than that of (-)-pantoprazole, and the mean maximum concentration and area under the plasma concentration-time curve from 0 to infinity for (+)-pantoprazole were 1.31- and 3.59-fold greater, respectively, than those for (-)-pantoprazole. These results indicate that the stereoselective metabolism of pantoprazole depends on S-mephenytoin 4'-hydroxylase (CYP2C19). The metabolism of (+)-pantoprazole was impaired to a greater extent than (-)-pantoprazole in the poor metabolizers.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2001

A new variant neuropathic type of Gaucher's disease characterized by hydrocephalus, corneal opacities, deformed toes, and fibrous thickening of spleen and liver capsules.

We report a new variant type of Gaucher's disease characterized by hydrocephalus, corneal opacities, deformed toes, gastroesophageal reflux, and fibrous thickening of splenic and hepatic capsules. This patient had 1 D409H allele. He differed from other reported cases with a 1342G to C (D409H) homozygous mutation (onset at 4 months, no cardiac involvement until the age of 12 years, and massive hepatosplenomegaly with fibrous thickening of spleen and liver capsules). Enzyme replacement therapy was given for 4 years, resulting in an improvement of visceral and hematologic abnormalities but no neurologic improvement.

Biopsy↗
PubMed2001

Repair of denture base resin using woven metal and glass fiber: effect of methylene chloride pretreatment.

STATEMENT OF PROBLEM: A durable repairing system for denture base fracture is desired to avoid recurrent fracture. Purpose. This study evaluated the strength and modulus of elasticity of repaired acrylic specimens reinforced with various processes. MATERIAL AND METHODS: Transverse strength and modulus of elasticity of repaired acrylic denture base specimens were evaluated with a 3-point bending test and compared with a heat-polymerized control. Autopolymerizing acrylic resin was used with woven metal fiber and glass fiber with and without methylene chloride surface treatment (n = 6 per group). The specimens were cut in half and fixed in a metal mold to obtain a space for placing the repairing resin. A cavity was prepared when metal or glass fiber was used. All specimens were stored in 37 degrees C distilled water for 48 hours before the test. All data were statistically analyzed with 1-way ANOVA, and differences among groups were analyzed with Fisher test (P< or =.05). RESULTS: The mean value of the transverse strength for the control was 87.2 MPa. The specimens repaired by glass fiber with methylene chloride surface treatment exhibited the highest transverse strength (96.8 MPa), which was significantly higher than that of the control (P< or =.05). The elastic modulus of the specimens repaired by glass fiber with methylene chloride surface treatment (4189.3 MPa) was significantly greater than that of the control (2683.7 MPa) at a 95% level of confidence. The values of transverse strength and elastic modulus were highest when the surface treatment was combined with a reinforcing glass fiber. CONCLUSION: Reinforcement with glass fiber and methylene chloride pretreatment produced transverse strength and a modulus of elasticity higher than the control.

Acrylic Resins↗
PubMed2001

Correction of the bilateral complete cleft lip: transformation to a unilateral incomplete cleft lip closure.

The complete lip alveolus and cleft palate is the most difficult of all bilateral clefts to treat because of the deformity of and tissue insufficiency in the prolabium. A bilateral concomitant procedure is impractical for treatment of this condition because of the problems that have to be resolved postoperatively, including a short columella, a lack of philtrum, labial horizontal and vertical insufficiency, and vermilion and alveolar vestibulum insufficiency. A two-stage procedure called the transformation method has been developed to circumvent these problems, and the authors present it here. With this method one side is closed completely using the maximum amount of tissue available. Concomitantly, incomplete closure is performed on the other side. The result at the end of the first stage of the procedure is a condition approximating unilateral incomplete closure. The results were obtained from 6 patients who underwent complete bilateral closure and were followed for at least 2 years with satisfactory results.

Child, Preschool↗
PubMed2001

Effects of beraprost sodium on canine cauda equina function and blood flow using a chronic spinal cord compression model.

Changes in blood flow after chronic compression were observed in 19 dogs after 10 mmHg compression for 1 week before and 1 hour after the intravenous administration of one of three doses of beraprost sodium (BPS; 30 ng x kg(-1) x min(-1), n = 7; 100 ng x kg(-1) x min(-1), n = 7; and 300 ng x kg(-1) x min(-1), n = 5). The speed of blood flow was calculated using a specially designed microscope equipped with a video camera. Dogs treated with BPS had lesser degrees of reduction in their nerve conduction velocity compared with controls. A vascular mechanism of injury likely explains why BPS-treated dogs had a lesser degree of reduction in their nerve conduction velocities compared with the control population.

Animals↗