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Kazuhiko Okuyama

Publications and source records attributed to Kazuhiko Okuyama.

12 recordsLinked to original sources
PubMed2006

Cerebral hemodynamics during the induction of antenatal periventricular leukomalacia by hemorrhagic hypotension in chronically instrumented fetal sheep.

OBJECTIVE: Our purpose was to determine the characteristics of cerebral ischemia during the induction of antenatal periventricular leukomalacia by hemorrhagic hypotension in premature fetal sheep. STUDY DESIGN: The hemorrhage group received an acute withdrawal of 40% of the fetoplacental blood volume (n = 7), whereas an isovolemic exchange transfusion was performed in the control group (n = 7). Changes in the total hemoglobin, oxy-hemoglobin, and deoxy-hemoglobin levels in the cerebral tissue were assessed with the use of near-infrared spectroscopy and compared statistically. RESULTS: Of 7 fetuses in the hemorrhage group, 5 exhibited periventricular leukomalacia but none in the control group (P < .05). In the hemorrhage group, both brain total-hemoglobin and deoxy-hemoglobin decreased seriously after insult, and the decreased levels persisted even after recovery of systemic blood pressure, whereas such drastic changes were not observed in the control group, suggesting the occurrence of reperfusion failure in the fetal brain in the hemorrhage group. CONCLUSION: The no-reflow phenomenon and successive reperfusion injuries after cerebral ischemia could be closely involved in the induction of antenatal periventricular leukomalacia in this experimental condition.

Animals↗
PubMed2005

CYP2C19 genotype affects diazepam pharmacokinetics and emergence from general anesthesia.

OBJECTIVES: Diazepam is widely used to relieve preoperative anxiety in patients. The objective of this study was to investigate the effects of polymorphism in CYP2C19 and the effects of CYP3A4 messenger ribonucleic acid (mRNA) content in blood on recovery from general anesthesia and on diazepam pharmacokinetics. METHODS: Sixty-three Japanese patients were classified into the following 3 genotype (phenotype) groups on the basis of polymerase chain reaction-restriction fragment length polymorphism analysis of CYP2C19 polymorphism: no variants, *1/*1 (extensive metabolizer [EM]); 1 variant, *1/*2 or *1/*3 (intermediate metabolizer [IM]); and 2 variants, *2/*2, *2/*3, or *3/*3 (poor metabolizer [PM]). We assessed the effects of these polymorphisms and of CYP3A4 mRNA content in the lymphocytes on the patients' recovery from general anesthesia. RESULTS: CYP2C19 genotyping analysis in the 63 subjects showed that 32%, 46%, and 22% of subjects were classified into the EM, IM, and PM groups, respectively. The PM subjects showed a larger area under the curve representing the concentration of diazepam over a 24-hour period (AUC(0-24)) (2088 +/- 378 ng/mL.h(-1), P = .0259), lower clearance of diazepam (0.049 +/- 0.009 L.h(-1).kg(-1), P = .0287), and longer emergence time (median, 18 minutes; 25th-75th percentile range, 13-21 minutes; P < .001) in comparison with subjects in the EM group (AUC(0-24), 1412 +/- 312 ng/mL; clearance, 0.074 +/- 0.018 L.h(-1).kg(-1); and emergence time, 10 minutes, 8-12 minutes [median and 25th-75th percentile range]). The IM group also showed a longer emergence time (median, 13 minutes; 25th-75th percentile range, 9-20 minutes; P < .001) and a larger variation in this parameter in comparison with the EM group. The distributions of the CYP2C19 genotype were significantly different between the 2 groups (rapid emergence <20 minutes, slow emergence >20 minutes) (P = .0148). The mean value of the CYP3A4 mRNA level in the slow-emergence group (mean +/- SD, 4.80 +/- 3.99 x10(-10)) was significantly lower than that of the rapid-emergence group (mean +/- SD, 12.50 +/- 11.90 x10(-10)) (P = .0315). However, there was no significant correlation between emergence time and CYP3A4 mRNA levels (r = 0.239, P = .0601). CONCLUSION: We found that the CYP2C19 genotype affects diazepam pharmacokinetics and emergence from general anesthesia and that the slow-emergence group possesses lower levels of CYP3A4 mRNA than are found in the rapid-emergence group.

Actins↗
PubMed2005

Effects of long term administration of KUR-1246, a selective beta(2)-adrenoceptor agonist, on pregnant sheep and their fetuses.

OBJECTIVE: To evaluate the safety of KUR-1246 as a tocolytic agent, we examined the effects of its long term infusion on respiratory and cardiovascular systems and general metabolism in pregnant sheep and their fetuses. DESIGN: Animal experiment with chronically instrumented ewes and their fetuses. SETTING: Center for animal experiments, Hokkaido University School of Medicine, Japan. SAMPLE: Eight Suffolk ewes at 117 to 120 days of gestation. METHODS: At 120-124 days of gestation, ewes (n= 4) were infused intravenously for 24 hours with KUR-1246 at 0.03 microg/kg/minute, a dose that completely inhibits oxytocin-induced uterine contractions in pregnant sheep. The controls received saline instead (n= 4). Statistical comparisons were carried out by repeated-measures ANOVA followed by Dunnett's test. MAIN OUTCOME MEASURES: Maternal and fetal values of heart rate, blood pressure, plasma electrolytes, glucose, insulin and non-esterified fatty acid levels, and blood gases and lactate level. RESULTS: The maternal plasma levels of KUR-1246 increased and reached a plateau at 15 hours or later from the start of the infusion, whereas the fetal levels of it were below the lower limit of quantification (0.1 ng/mL) throughout the experiment. Significant differences over time between the ewes that had received with KUR-1246 and the controls were found for the following parameters: maternal heart rate, blood lactate, plasma glucose, and plasma insulin levels, and fetal plasma glucose and plasma insulin levels (P < 0.05). In the KUR-1246 treated ewes, significant changes from the pre-infusion value were detected in maternal blood lactate and fetal plasma glucose levels within 6 hours from the start of the infusion (P < 0.05). No significant differences were observed in other parameters in either ewes or fetuses. CONCLUSION: The physiologic changes induced by a 24-hour infusion of KUR-1246 were transient and considered to be within the compensatory capacity in both pregnant ewes and their fetuses, suggesting that KUR-1246 is a potentially safe tocolytic agent for use by long term infusion.

Acetamides↗
PubMed2004

Postnatal management for prenatally diagnosed choledochal cysts.

PURPOSE: The aim of this study was to determine an appropriate postnatal management plan for prenatally diagnosed congenital biliary dilatation (CBD). METHODS: Between 1962 and 2002, 5 (5.9 %) of 85 patients had CBD diagnosed prenatally and were examined clinically. Of these 5 patients, 2 (group A) underwent delayed primary definitive surgery after percutaneous transhepatic cholangiodrainage (PTCD), 1 (group B) underwent early definitive surgery in the neonatal period, and 2 (group C) underwent delayed primary definitive surgery without PTCD in early infancy (within 6 months after birth). The clinical data, operative findings, intra- and postoperative complications, and follow-up were evaluated in these 3 groups. RESULTS: There were no postoperative complications, such as catheter-related complications, in group A. However, there was adhesion around the choledochal cyst, and the operation was therefore difficult in group A. The diameter of the anastomosis in the hepaticojejunostomy was small, and the cyst wall was thin in group B. Consequently, anastomotic leakage of the hepaticojejunostomy occurred in group B. Neither operative nor postoperative complications such as anastomotic leakage or stenosis occurred in group C. Slight fibrosis of Glisson's sheath was seen in 2 patients of groups A and C. No liver cirrhosis was seen in any group. CONCLUSIONS: The authors propose that asymptomatic patients should undergo elective definitive surgery by 6 months of age. For symptomatic patients, especially when a differential diagnosis of type I cystic biliary atresia is doubtful, early definitive surgery is needed before 2 months of age. PTCD appears to be indicated only under certain circumstances, and delayed primary definitive surgery should be performed as early as possible thereafter.

Anastomosis, Surgical↗
PubMed2004

[Congenital anomalies of the genitourinary tract].

Genitourinary tract anomalies found at birth arise from a variety of sex differentiation disorders occurred during fetal development. It is important to know and identify common congenital anomalies of genitalia for disclosing underlying genetic and/or endocrine disorders of newborn at very early stage of life as well as for determining proper sex of neonate. This article presents several genital anomalies from an obstetric point of view and simply describes their handlings.

Female↗
PubMed2003

Prenatal diagnosis and fetal therapy of congenital cystic adenomatoid malformation type I of the lung: a report of five cases.

We experienced five pregnancy cases with type I congenital cystic adenomatoid malformation (CCAM) of fetuses and summarized here their clinical characteristics, pregnancy outcomes, and fetal therapies. Four of five cases were prenatally diagnosed using magnetic resonance imaging (MRI) as having lung abnormality, and the remaining case was prenatally diagnosed as having congenital diaphragmatic herniation (CDH). One fetus underwent the puncture of cysts in the lung, and two fetuses received in utero thoracoshunts between cysts and the amniotic fluid cavity (thoracoamniotic shunt). One pregnancy ended in artificial termination at 17 gestational weeks, and 4 pregnancies succeeded in live births. All these 4 infants underwent surgical operations for CCAM, and 1 infant underwent an additional operation for CDH. The MRI examinations were useful to prenatally identify CCAM, and the in utero thoracoamniotic shunt appears to be beneficial in preventing lung hypoplasia in the affected fetuses.

Adult↗
PubMed2002

KUR-1246, a novel beta(2)-adrenoceptor agonist, as a tocolytic agent.

OBJECTIVE: To examine the effects of KUR-1246 on oxytocin-induced uterine contractions, the cardiovascular system, and general metabolism of pregnant sheep and their fetuses. METHODS: At 123-125 days' gestation, ewes (n = 8) were infused with oxytocin (1.0 mU/kg/minute) to induce uterine contractions. One hour later, KUR-1246 was infused for 3 consecutive hours beginning at a dose of 0.001 microg/kg/minute for 30 minutes and increasing stepwise every 30 minutes to 0.3 microg/kg/minute in the KUR-1246 group (n = 4). The control received saline instead (n = 4). Statistical comparisons of changes with time in the physiologic parameters between the two groups were carried out (analysis of variance). RESULTS: KUR-1246 suppressed oxytocin-induced uterine contractions more than 90% at doses over 0.03 microg/kg/minute. Significant differences between the two groups were found at high doses over 0.03 microg/kg/minute for the following parameters: maternal heart rate, diastolic blood pressure, mean blood pressure, base excess, blood K(+), blood lactate, plasma glucose, plasma insulin, plasma nonesterified fatty acid levels, and fetal plasma glucose and plasma insulin levels. CONCLUSION: KUR-1246 significantly inhibited oxytocin-induced uterine contractions at doses over 0.03 microg/kg/minute and showed reduced cardiovascular and metabolic side effects compared with ritodrine hydrochloride studied earlier in pregnant sheep.

Acetamides↗
PubMed2002

Analyses of factors contributing to vulnerability to antenatal periventricular leukomalacia induced by hemorrhagic hypotension in chronically instrumented fetal sheep.

Our purpose was to determine factors contributing to vulnerability to antenatal periventricular leukomalacia (PVL) induced by hemorrhagic hypotension in premature fetal sheep. Systemic hypotension was induced in 10 fetal sheep by acutely withdrawing 35% to 40% of the fetoplacental blood volume at 113 d gestation. Brains were processed for histologic analysis 6 d after the insult. Statistical comparisons of physiologic parameters between fetuses suffering from PVL (n = 5) and those without PVL (n = 5) were performed. Significant correlations were found between induction of PVL and fetal brain weight, changes in fetal mean blood pressure over time, base excess, oxygen content, hematocrit, and plasma arginine vasopressin (AVP) levels in fetal abdominal aortic blood. Brain developmental stage, the magnitude of induced systemic hypotension, and baseline blood oxygen content were important intrinsic factors in the induction of antenatal PVL by hemorrhagic hypotension in premature fetal sheep.

Animals↗