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K Okuyama

Publications and source records attributed to K Okuyama.

At least 19 recordsLinked to original sources
PubMed2006

Finasteride 1 mg has no inhibitory effect on omeprazole metabolism in extensive and poor metabolizers for CYP2C19 in Japanese.

OBJECTIVE: To examine the inhibitory effect of finasteride 1 mg on the metabolism of omeprazole in genetically determined extensive (EMs) and poor metabolizers (PMs) for CYP2C19 in young healthy Japanese male subjects. METHODS: Twenty-four volunteers participated in this study, among whom 12 were homozygous EMs and 12 were PMs for CYP2C19. A single center, controlled, randomized, open, crossover study with a 5 day washout between the two study periods was performed. Each of the six EMs and PMs received a single oral 20 mg dose of omeprazole on day 1 (treatment I). After a 5 day washout period, these subjects received 1 mg of finasteride once a day for three consecutive days, and a single oral 20 mg dose of omeprazole was co-administered on day 3 (treatment II). The 12 other EMs and PMs received treatments I and II in reverse. Plasma samples were collected for up to a 12 hours postdose of omeprazole, and the pharmacokinetic parameters of omeprazole were determined. RESULTS: The geometric mean ratio (GMR) for the AUC((0-12 hr)) of omeprazole when co-administered with finasteride/omeprazole alone is 1.13 (90%CI, 1.03, 1.25) and 0.96 (0.88, 1.05) in EMs and PMs, respectively. Finasteride did not significantly alter C(max), T(max) and t(1/2) in both genotypes. CONCLUSION: Finasteride 1 mg, widely used for the treatment of androgenetic alopecia in men, did not meaningfully increase omeprazole exposure (20 mg) in both EMs and PMs for CYP2C19. These results indicate that finasteride does not meaningfully inhibit CYP2C19 activity in vivo at the dose of 1 mg.

Adult↗
PubMed2005

Optimal dose and target trough level in cyclosporine and tacrolimus conversion in renal transplantation as evaluated by lymphocyte drug sensitivity and pharmacokinetic parameters.

We evaluated the relative clinical potency of cyclosporine (CyA) and tacrolimus (Tac) using pharmacodynamic and pharmacokinetic parameters of the drug to obtain the most suitable converting dose and target trough level. The relative pharmacodynamic potency was examined by the mean ratio of drug concentrations giving 50% inhibition of blastogenesis of lymphocytes (IC50) in 66 chronic renal failure patients. The relative potency estimated from clinical pharmacokinetic parameters was examined by the mean ratio of each pharmacokinetic parameter value of CyA versus Tac. The pharmacokinetic parameters were estimated by 12-hour monitoring of drug blood concentrations in seven CyA patients and seven Tac patients. The mean IC50 ratio of CyA and Tac (CyA/Tac of IC50) was 25.1. The mean area under the concentration-time curve (AUC) ratio (CyA/Tac of AUC) was 25.5, the mean trough level (C(min)) ratio (CyA/Tac of C(min)) was 13.2, and the mean dose per body weight ratio was 25.2. The relative potency estimated from AUC that is the most reliable pharmacokinetic parameter for the estimation of clinical efficacy of calcineurin inhibitors appeared to agree with the relative pharmacodynamic potency estimated from IC50. The data suggest that TAC 25-fold more potent than CyA, which represents a suitable converting dose ratio, and that target trough level of CyA is about 13-fold greater than Tac based on CyA/Tac of C(min). We conclude that these relative values may be useful to estimate the suitable dose and target trough levels to convert between CyA and Tac.

Area Under Curve↗
PubMed2005

Evaluation of appropriate blood level in continuous intravenous infusion from trough concentrations after oral administration based on area under trough level in tacrolimus and cyclosporine therapy.

The target blood concentrations of tacrolimus (TAC) and cyclosporine (CYA) during continuous intravenous infusion (C(ss)) have been determined based on clinical experience. However, it is desirable that C(ss) should be set so that the AUC after intravenous infusion is equal to the AUC after oral administration (AUC(po)). Accordingly, we performed 12-hour monitoring of blood concentrations to calculate C(ss) from the blood trough levels (C(TL)) on 15 kidney recipients administered TAC and 12 recipients administered CYA (Neoral). We used an area under the trough level (AUTL) as a new pharmacokinetic parameter. The C(ss) was evaluated from C(TL), AUC(po), and AUTL was calculated to be C(ss) = C(TL) x (AUC(po)/AUTL). In addition, AUTL/AUC(po) ratio and blood peak/trough level ratio (C(max)/C(min)) were examined to compare pharmacokinetics of TAC and CYA. The formula for TAC was C(ss) = C(TL) x 1.40 and that for CYA, C(ss) = C(TL) x 2.55. The calculated target C(ss) of TAC was 1.40 times that of C(TL), which was similar to the present clinical C(TL). In contrast, the calculated target C(ss) of CYA was 2.55 times the C(TL), and therefore an extremely high C(ss) was necessary to obtain a sufficient AUC that will be available after oral administration. Consequently, intravenous administration of CYA twice a day was considered to be more appropriate to obtain sufficient CYA pharmacokinetics, rather than a continuous intravenous administration. We conclude that the formula, C(ss) = C(TL) x (AUC(po)/AUTL) was useful to calculate the target blood concentration of calcineurin inhibitors when changing from continuous intravenous infusion to oral administration of these drugs.

Administration, Oral↗
PubMed2005

Pharmacokinetic differences between morning and evening administration of cyclosporine and tacrolimus therapy.

We performed 24-hour monitoring of cyclosporine (NEO) and tacrolimus (TAC) blood concentrations, evaluating pharmacokinetic parameters and characterizing circadian variations. The monitoring was performed in 10 instances on nine patients administered NEO and 12 out of 11 patients administered TAC. All cases were administered equally divided doses of drugs twice daily orally. Blood samples were taken before and 1, 2, 3, 4, 6, and 12 hours after NEO or TAC administration in the morning and evening. The pharmacokinetic parameters were compared between morning and evening administrations of both drugs. AUC0-12, AUC0-4, C(max), C2, and C(max)/C(min) of NEO and TAC were significantly lower during the evening compared with morning administrations. C(min) values were significantly higher in the evening. T(max) of NEO was longer in evening, although there was not a significant difference; T(max) of TAC was significantly longer in the evening. We found that NEO and TAC administrations in the evening resulted in reduced bioavailability and delayed absorption when compared with drug administrations in the morning. It was thought that the difference in bioavailability between morning and evening administrations was smaller with TAC, because TAC shows lower peak levels and a flatter blood concentration curve than NEO. C(min) was higher after evening administration than morning because of delayed absorption, though the bioavailability of both drugs decreased in the evening. These results suggest that we have to appreciate apparently high trough levels.

Administration, Oral↗
PubMed2004

Bone mineral density of the lumbar spine is associated with TNF gene polymorphisms in early postmenopausal Japanese women.

We investigated the relationships between tumor necrosis factor (TNF) gene polymorphism, circulating TNF-alpha (TNF-alpha) concentrations, and bone mineral density (BMD) in the lumbar spine. TNF gene polymorphisms studied were the Nco I polymorphism within the first intron of TNF-beta (TNF-beta) and three single nucleotide polymorphisms in the promoter region of the TNF-alpha gene, at positions -857, -863, and -1031. Allelic variants of the TNF gene were identified using restriction fragment length polymorphism (RFLP) analysis in 177 postmenopausal Japanese women within 10 years after menopause, aged 56.4 +/- 4.5 years (mean +/- SD). A significantly higher prevalence of the alleles TNF-alpha-863A (20.3% versus 9.9%) and TNF-alpha-1031C (21.3% versus 12.4%) was seen in the low BMD group (Z-score < 0, n = 91) than in the high BMD group (0 < Z-score, n = 86). In genotype analysis, although difference did not reach a significant level, women with the rarest allelic variants, i.e., homozygous TNFbl, TNF-alpha-863A, and TNF-alpha-1031C, showed the lowest BMD Z-scores. Women with another rarest allelic variant, TNF-alpha-857T/T had significantly lower BMD Z-scores than did women with TNF-alpha-857C/T or -857C/C. The BMD Z-score decreased significantly with an increase in the total number of such rare alleles. Serum concentrations of TNF-alpha did not differ significantly among groups divided by genotypes. Multiple linear regression analysis revealed that the total number of rare alleles, in addition to the body mass index and the number of years since menopause, was an independent predictor of the BMD. These presumptive functional polymorphisms of the TNF gene may be associated with the lumbar spine BMD in early postmenopausal Japanese women.

Absorptiometry, Photon↗
PubMed2003

Nitrous oxide decreases shivering threshold in rabbits less than isoflurane.

BACKGROUND: Comparable minimum alveolar concentration (MAC) fractions of volatile anaesthetics produce similar thermoregulatory impairment. Nitrous oxide, however, decreases the vasoconstriction threshold less than sevoflurane or isoflurane. We tested the hypothesis that nitrous oxide also decreases shivering threshold less than isoflurane alone or in combination. METHODS: Twenty-four rabbits were assigned randomly to one of three 0.3 MAC anaesthetic regimens: (i) nitrous oxide 69%; (ii) nitrous oxide 35% and isoflurane 0.3%; or (iii) isoflurane 0.6%. Body temperature was lowered by perfusing 10 degrees C water through a U-shaped thermode positioned in the colon. Shivering was evaluated by inspection. RESULTS: The rabbits anaesthetized with nitrous oxide alone shivered at 37.0 (0.5) degrees C (P<0.01 vs other groups). In those given the nitrous oxide and isoflurane combination, the shivering threshold was 36.4 (0.5) degrees C and that in the isoflurane group was 35.9 (0.4) degrees C. CONCLUSION: This study indicates that nitrous oxide reduces the shivering threshold less than isoflurane.

Anesthetics, Inhalation↗
PubMed2001

Refined molecular and crystal structure of silk I based on Ala-Gly and (Ala-Gly)(2)-Ser-Gly peptide sequence.

The molecular and crystal structure of one of the crystalline modifications of Bombyx mori, silk I, was determined by x-ray diffraction method. Cell dimensions are essentially the same as those found in the synthetic model peptide poly(L-Ala-Gly). The (straight phi, psi) values of L-Ala and Gly in the repeating unit are (-112 degrees, -6 degrees ), and (71 degrees, -99 degrees ) respectively, which are in the Bridge and the forth quadrant regions of the Ramachandran map, respectively. The observed molecular conformation in the present study has a "crank-shaft" or a S-shaped zigzag arrangement, leading to a remarkable agreement of observed and calculated structure amplitudes for both dipeptide and hexapeptide sequences, and has a reasonable hydrogen bond networks. Obtained (straight phi, psi) values are quite different from those reported by Lotz and Keith, even though overall appearances are quite similar to each other. In spite of intra- and intermolecular hydrogen-bond networks, silk I structure changes easily to the silk II by a mechanical deformation. This fragility may be due to the above peculiar crank-shaft conformation deduced from the alternating structure of alanine and glycine.

Animals↗
PubMed2001

Prognostic significance of combined conventional and immunocytochemical cytology for peritoneal washings in endometrial carcinoma.

BACKGROUND: Noncancerous cells simulating adenocarcinoma cells may interfere with the analysis of peritoneal cytology (PC) in patients with endometrial carcinoma. Immunocytochemistry (ICC) may improve the diagnosis of PC. METHODS: PC slides from 115 patients with endometrial carcinoma were reviewed. Suspicious or positive cell clusters were recovered with a cell transfer method and were subjected to ICC for MOC-31, cytokeratin 5/6, and p53. Conventional Papanicolaou staining and ICC results were compared directly on the same cells. RESULTS: By combined conventional and immunocytochemical PC (CONV-ICC-PC), cytodiagnosis was positive in 18 of 115 patients (15.7%) and suspicious in 3 of 115 patients (2.6%). According to a multivariate Cox regression analysis of patients with tumors confined to the uterus that included grade, myometrial invasion, cervical involvement, and CONV-ICC-PC, only CONV-ICC-PC was an independent prognostic factor (P < 0.05). A multivariate analysis for all of the patients studied that compared CONV-ICC-PC with staging variables revealed that only peritoneal metastasis (P < 0.0001) and lymph node metastasis (P < 0.01) were independent prognostic factors. When peritoneal metastases were excluded, CONV-ICC-PC (P < 0.01) and lymph node metastasis (P < 0.0025) were the independent prognostic factors. By cell transfer and p53 immunostaining in samples from 14 patients with malignant cells in their peritoneal washings, no deaths occurred among 5 patients with negative p53, whereas 5 of 9 patients with positive p53 died of disease at the time of data analysis. CONCLUSIONS: MOC-31 immunostaining improves the diagnosis of PC in endometrial carcinoma. Positive PC is an important prognostic factor for patients with endometrial carcinoma confined to the uterus. The p53 positive cells in PC have possible prognostic significance.

Adult↗
PubMed2001

Alpha-fetoprotein microheterogeneity: a potential biochemical marker for Down's syndrome.

Our purpose was to examine the utility of analyzing alpha-fetoprotein (AFP) microheterogeneity assessed by lectin affinity in Down's syndrome (DS) screening. Maternal sera and amniotic fluids were collected from 18 women who were carrying DS fetuses and 70 unaffected pregnancies around 16 weeks of gestation. The percentages of AFP which reacted with Lens culinaris agglutinin (AFP-L2,3) were determined by lectin affinity electrophoresis. AFP-L2,3 levels were significantly increased (P<0.0001) in both maternal serum and amniotic fluid from DS-affected versus unaffected pregnancies. The fractional areas under the receiver operating characteristic curves were 0.835 and 0.700 (P=0.106) for AFP-L3 and AFP MoM (multiples of the median) in maternal serum. No correlation was found between AFP-L3 and AFP MoM in maternal serum (r=0.006). Our data suggest that the measurement of AFP-L3 in maternal serum is a potential biochemical marker for DS.

Amniotic Fluid↗
PubMed2001

Histopathological prognostic factors of adult granulosa cell tumors of the ovary.

BACKGROUND: The prognostic factors of adult granulosa cell tumor (AGCT) have not been well defined. METHODS: In 27 AGCT patients, we examined clinical stage, microscopic patterns, mitotic index (MI), and lymph-vascular space invasion (LVSI) to determine whether these factors were related to disease-free survival (DFS) of patients with AGCT. We also performed immunohistochemical examination for p53. RESULTS: Seventeen cases represented stage I tumors, four stage II, five stage III, and one stage IV. Patients with stage I disease had more favorable prognosis than those with stage II to IV disease (p=0.034). There was no relation between the microscopic patterns and the DFS. The MI, which was categorized into < or =3/10 high power field (HPF) and > or =4/10 HPF, was significantly related to patients DFS (p<0.0005). The DFS time for patients with moderate or prominent LVSI was significantly shorter than that for patients with no or minimal LVSI (p<0.0001). By multivariate analysis, MI and LVSI were shown to be independent prognostic factors. Five of seven patients with recurrent tumor had extrapelvic spread; two in the abdominal cavity and three in the liver. CONCLUSION: The results of this study suggest that prognosis for patients with AGCT depends on the MI and LVSI. During the follow-up period of patients, they need to be examined for distant metastasis including liver.

Adolescent↗
PubMed2001

Alcohol and the pancreas.

This article represents the proceedings of a workshop at the 2000 ISBRA Meeting in Yokohama, Japan. The presentations were (1) Phenotypic alteration of myofibroblast during ethanol-induced pancreatic injury: its relation to bFGF, by Masahiko Nakamura, Kanji Tsuchimoto, and Hiromasa Ishii; (2) Activation of pancreatic stellate cells in pancreatic fibrosis, by Paul S. Haber, Gregory W. Keogh, Minoti V. Apte, Corey S. Moran, Nancy L. Stewart, Darrell H.G. Crawford, Romano C. Pirola, Geoffrey W. McCaughan, Grant A. Ramm, and Jeremy S. Wilson; (3) Pancreatic blood flow and pancreatic enzyme secretion on acute ethanol infusion in anesthetized RAT, by H. Nishino, M. Kohno, R. Aizawa, and N. Tajima; (4) Genotype difference of alcohol-metabolizing enzymes in relation to chronic alcoholic pancreatitis between the alcoholic in the National Institute on Alcoholism and patients in other general hospitals in Japan, by K. Maruyama, H. Takahashi, S. Matsushita, K. Okuyama, A. Yokoyama, Y. Nakamura, K. Shirakura, and H. Ishii; and (5) Alcohol consumption and incidence of type 2 diabetes, by Katherine M. Conigrave, B. Frank Hu, Carlos A. Camargo Jr, Meir J. Stampfer, Walter C. Willett, and Eric B. Rimm.

Alcohol Drinking↗
PubMed2001

Plasma lidocaine concentrations during continuous thoracic epidural anesthesia after clonidine premedication in children.

UNLABELLED: There is no report concerning oral clonidine's effects on epidural lidocaine in children. Therefore, we performed a study to assess the concentrations of plasma lidocaine and its major metabolite (monoethylglycinexylidide [MEGX]) in children receiving continuous thoracic epidural anesthesia after oral clonidine premedication. Ten pediatric patients, aged 1-9 yr, were randomly allocated to the Control or Clonidine 4 microg/kg group (n = 5 each). Anesthesia was induced and maintained with sevoflurane in oxygen and air (FIO2 40%). Epidural puncture and tubing were carefully performed at the Th11-12 intervertebral space. An initial dose of 1% lidocaine (5 mg/kg) was injected through a catheter into the epidural space, followed by 2.5 mg x kg(-1) x h(-1). Plasma concentrations of lidocaine and MEGX were measured at 15 min, 30 min, and every 60 min for 4 h after the initiation of continuous epidural injection. The concentrations of lidocaine and MEGX were measured using high-pressure liquid chromatography with ultraviolet detection. Hemodynamic variables were similar between members of the Control and Clonidine groups during anesthesia. The Clonidine group showed significantly smaller lidocaine concentrations (p < 0.05) and the concentration of MEGX tended to be smaller in the plasma of the Clonidine group for the initial 4 h after the initiation of epidural infusion. In conclusion, oral clonidine preanesthetic medication at a dose of 4 microg/kg decreases plasma lidocaine concentration in children. IMPLICATIONS: Oral clonidine decreases the plasma lidocaine concentration in children. Our finding may have clinical implications in patients receiving continuous epidural anesthesia. Additionally, perhaps an additional margin of safety regarding lidocaine toxicity is gained through the use of oral clonidine in children who will receive epidural lidocaine.

Administration, Oral↗
PubMed2001

Total spondylectomy for primary malignant, aggressive benign, and solitary metastatic bone tumors of the thoracolumbar spine.

The records of 14 patients with malignant or aggressive benign vertebral tumors of the thoracolumbar spine who underwent total spondylectomy (TS) were evaluated retrospectively. Total spondylectomy was performed by bisecting the affected vertebra through the pedicle using fine threadwire saws and removing the vertebra en bloc through the posterior procedure alone or the one-stage anteroposterior combined procedure. Remarkable pain relief and ambulation after surgery were achieved in all 14 patients. No serious complications occurred. Nerve roots were sacrificed in seven cases. A marginal surgical margin was achieved in 10 cases and an intralesional surgical margin was achieved in four. At the site of the osteotomized pedicle, the surgical margin was marginal, with the possibility of tumor-cell contamination in 10 cases. Local recurrence was found in three cases of posterior total spondylectomy at 0.3 to 3.5 years (mean, 3.2 years) follow-up evaluation at the other site of the osteotomized pedicle. These results suggest that this type of total spondylectomy is effective in controlling local recurrence without incurring major complications and is a clinically useful procedure.

Adolescent↗
PubMed2001

Improving the pullout strength of pedicle screws by screw coupling.

The objective of this study was to determine the effect of pedicle screw coupling on the pullout strength of pedicle screws in the osteoporotic spine. The vertebral bone mineral density (BMD) of 33 cadaveric lumbar vertebrae were measured by quantitative computed tomography. Pedicle screws were inserted into each pedicle. The pullout strength and displacement of the screws, without coupling and with single or double couplers, were studied, and the relationship between pullout strength and BMD was analyzed. The average pullout strength of the pedicle screws without screw coupling was 909.3 +/- 188.6 N (n = 9), that coupled with a single coupler was 1,409.0 +/- 469.1 N (n = 9), and that with double couplers was 1,494.0 +/- 691.6 N (n = 9). The pullout strength of the screws coupled with single or double couplers was significantly greater than that of screws without couplers (p < 0.01); however, there was no significant difference between the groups of single and double couplers. The improvement of pullout strength by screw coupling was significant in a test group with BMD of more than 90 mg/ml (p < 0.01), but was not in the group with BMD less than 90 mg/ml (p = 0.55). These results suggest that the coupling of pedicle screws improves pullout strength; however, the effect tends to be less significant in severely osteoporotic spines.

Aged↗
PubMed2001

[Evaluation of immunochromatography based rapid detection kit of rotavirus and adenovirus].

We investigated the usefulness of Rapidtesta Rota-Adeno (Daiichi Pure Chemicals Co., Ltd., Japan) for rapid detection of group A rotavirus and adenovirus simultaneously using immunochromatography with clinical samples. In investigation of the reaction of the kit to 5 strains of group A rotavirus, 13 strains of adenovirus and other intestinal viruses, specific lines were formed in red to group A rotavirus and blue to adenovirus. No cross reaction was observed with other intestinal virus. In measurement of detection limit, group A rotavirus (SA11) was detected at 10(4.4)TCID50/ml, serotype 3 adenovirus at 10(4.45)TCID50/ml. The detection limit of the kit was similar to other immunochromatographic assay or enzyme immnoassay kits and approximately 10 times higher than that of kits using latex agglutination test. In comparison with other testing kits in clinical samples, the concordance with other immunochromatographic assay was 99.2% (121/122) in group A rotavirus and 98.6% (138/140) in adenovirus. The rate of concordance with latex agglutination test kit was 94.5% (69/73) in group A rotavirus and 92.3% (84/91) in adenovirus. The kit had high rates of concordance with other immunochromatographic assay kits and higher virus detection rates than those of latex agglutination test kits. Rapidtesta Rota-Adeno is able to detect group A rotavirus and adenovirus simply and rapidly. In addition, the two kinds of virus can be easily differentiated by color difference in reaction lines, suggesting that the kit is useful in clinical diagnosis.

Adenoviridae↗
PubMed2001

Crystalline behavior of chitosan organic acid salts.

The crystal structures of chitosan acid salts were studied by X-ray diffraction measurements on a fiber diagram and a new procedure to obtain an anhydrous polymorph of chitosan was found. The salts prepared by immersing a chitosan into a mixture of acid solution and isopropanol were classified into two types (Types I and II) depending on their conformation. Molecular conformation of the Type I salt retains the extended 2-fold helical structure of the original chitosan, but that of Type II salt is a twisted 2-fold helix. All the Type II salts changed to the anhydrous "Annealed" polymorph of chitosan when soaking in 75% aqueous isopropanol, but when the Type I salts were immersed in the solution, they returned to the hydrated "Tendon" polymorph which is that of the original chitosan. The strange transformation observed in Type II salt may be related to the stability of the molecular conformation of chitosan in the salt.

Acids↗
PubMed2001

Naturally-occurring Neospora caninum infection in an adult sheep and her twin fetuses.

Neospora caninum tissue cysts were found in the brains of surgically delivered twin fetuses at 119 days of gestation. In the brains of both fetuses, there was an inflammatory reaction involving perivascular cuffings of mononuclear cells, glial nodules. The dam of these fetuses died because of metritis. Histopathological examination of the ewe revealed N. caninum tissue cysts and focal gliosis with mononuclear cell cuffings. A N. caninum-specific DNA fragment was detected in a brain homogenate of the ewe by the polymerase chain reaction method. This is the first report of N. caninum infection in twin ovine fetuses and in an adult sheep.

Animals↗