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1.
Int J Gynaecol Obstet ; 156(1): 64-70, 2022 Jan.
Article in English | MEDLINE | ID: mdl-33471369

ABSTRACT

OBJECTIVE: To determine the association between cervical polyps in early pregnancy and late abortion and spontaneous preterm birth (SPTB). We also aimed to explore the relationship between cervical polyps and cervical insufficiency in the second trimester. METHODS: We conducted a retrospective cohort study of 2941 singleton pregnant women between January 2010 and December 2015. The frequency of late abortion and SPTB (before 28, 34, or 37 weeks of pregnancy) was compared between the two groups of 142 (4.8%) patients who had cervical polyps early in the pregnancy (P group) and 2799 who did not (non-P group). Multivariate analysis was performed to identify risk factors for late abortion and SPTB. RESULTS: The incidence of late abortion and SPTB was significantly higher in the P group than in the non-P group. Cervical polyps in early pregnancy were selected as independent risk factors for late abortion and SPTB before 28, 34, or 37 weeks of pregnancy. The P group had a significantly higher rate of cases requiring therapeutic cervical cerclage than the non-P group. CONCLUSION: Cervical polyps in early pregnancy are risk factors for late abortion and SPTB. They are also associated with the occurrence of cervical insufficiency.


Subject(s)
Cerclage, Cervical , Premature Birth , Uterine Cervical Incompetence , Cervical Length Measurement , Female , Humans , Infant, Newborn , Pregnancy , Premature Birth/epidemiology , Premature Birth/etiology , Retrospective Studies , Risk Factors , Uterine Cervical Incompetence/epidemiology
2.
PLoS One ; 15(3): e0230488, 2020.
Article in English | MEDLINE | ID: mdl-32176740

ABSTRACT

Pregnant women with diabetes mellitus (DM) are at high risk for hypertensive disorder of pregnancy (HDP). Women with poor control DM sometimes have heavy-for-dates infants. However, women with HDP sometimes have light-for-dates infants. We aim to clarify the relationship between glycemic control and fetal growth in women with DM and/or subsequent HDP. Of 7893 women gave singleton birth at or after 22 gestational weeks, we enrolled 154 women with type 1 DM (T1DM) or type 2 DM (T2DM) whose infants did not have fetal abnormalities. Among women with T1DM or T2DM, characteristics of the three groups (with HDP, without HDP, and with chronic hypertension [CH]) were compared. No women with T1DM had CH, but 19 (17.4%) of 109 with T2DM did. HDP incidence was similar between women with T1DM (22.2%) and T2DM without CH (16.7%). Among women with T1DM, the incidences of fetal growth restriction (FGR) with and without HDP were similar. However, among women with T2DM without CH, this incidence was significantly higher among those with HDP (33.3%) than among those without HDP (5.3%), was significantly more common with HbA1c levels at first trimester ≥ 7.2% (33.3%) than with those < 7.2% (5.6%), and significantly more numerous without pre-pregnancy therapies for DM (23.3%) than with them (3.3%). Among women with T2DM and HDP, those with FGR had smaller placenta SDs and higher insulin dosages at delivery than those without light-for-dates. In multivariate analysis, the presence of diabetic nephropathy was a predictor of T1DM and HDP (P = 0.0105), whereas HbA1c levels ≥ 7.2% before pregnancy was a predictor of T2DM and HDP (P = 0.0009). Insulin dosage ≥ 50U/day at delivery (P = 0.0297) and the presence of HDP (P = 0.0116) independently predicted T2DM, HDP, and FGR development. Insufficient pre-pregnancy treatment of DM increased the risk of HDP.


Subject(s)
Blood Glucose/metabolism , Diabetes Mellitus, Type 1 , Diabetes Mellitus, Type 2 , Fetal Growth Retardation , Insulin/administration & dosage , Pre-Eclampsia , Pregnancy in Diabetics , Adult , Chronic Disease , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/drug therapy , Diabetes Mellitus, Type 1/epidemiology , Diabetes Mellitus, Type 1/pathology , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/pathology , Female , Fetal Growth Retardation/blood , Fetal Growth Retardation/drug therapy , Fetal Growth Retardation/epidemiology , Fetal Growth Retardation/pathology , Humans , Placenta/metabolism , Placenta/pathology , Pre-Eclampsia/blood , Pre-Eclampsia/drug therapy , Pre-Eclampsia/epidemiology , Pre-Eclampsia/pathology , Pregnancy , Pregnancy in Diabetics/blood , Pregnancy in Diabetics/drug therapy , Pregnancy in Diabetics/epidemiology , Pregnancy in Diabetics/pathology , Retrospective Studies , Risk Factors
3.
J Obstet Gynaecol Res ; 43(2): 257-264, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27995667

ABSTRACT

AIM: The aim of this study was to determine whether women with pregnancy-induced antithrombin deficiency (PIATD) had higher risk of liver dysfunction in the absence of thrombocytopenia. METHODS: We carried out a retrospective observational study at five centers in all 129 women with incidentally found PIATD among 5249 maternities and 129 control women without PIATD matched for number of fetuses and gestational week at delivery. PIATD was diagnosed in women with antenatal antithrombin (AT) activities of ≤75% followed by a further decrease to ≤65% peripartum. Liver dysfunction was defined as serum aspartate aminotransferase >  45 IU/L concomitant with lactate dehydrogenase >  400 IU/L. Thrombocytopenia was defined as platelet count < 120 × 109 /L. RESULTS: Thrombocytopenia (22% [28/129] vs 5.4% [7/129], P =  0.0001) and liver dysfunction (16% [20/129] vs 0.0% [0/129], P =  0.0000) occurred significantly more often in PIATD than in control women. Of the 20 women with liver dysfunction, 15 (75%) had PIATD, but not thrombocytopenia. Thus, even in the absence of thrombocytopenia, liver dysfunction occurred significantly more often in PIATD than in control women (15% [15/101] vs 0.0% [0/122], respectively, P =  0.0000). The relative risk (95% confidence interval) of liver dysfunction was 28.6 (1.64-500) for women with AT activity of 60-65% and 52.4 (3.17-865) for women with AT activity of <60%, compared to women with AT activity ≥66%. CONCLUSION: PIATD can occur in the absence of thrombocytopenia and PIATD women had higher risk of liver dysfunction even in the absence of thrombocytopenia.


Subject(s)
Antithrombin III Deficiency/epidemiology , Liver Diseases/epidemiology , Pregnancy Complications, Hematologic/epidemiology , Thrombocytopenia/epidemiology , Adult , Comorbidity , Female , Humans , Pregnancy , Retrospective Studies
4.
Int J Gynecol Cancer ; 25(4): 751-7, 2015 May.
Article in English | MEDLINE | ID: mdl-25723779

ABSTRACT

OBJECTIVE: Lower extremity lymphedema (LEL) is a major long-term complication of radical surgery. We aimed to estimate the incidence and grading of LEL in women who underwent lymphadenectomy and to evaluate risk factors associated with LEL. MATERIALS AND METHODS: We retrospectively reviewed 358 patients with cervical, endometrial, and ovarian cancer who underwent transabdominal complete systematic pelvic and para-aortic lymphadenectomy between 1997 and 2011. Lower extremity lymphedema was graded according to criteria of the International Society of Lymphology. Incidence of LEL and its correlation with various clinical characteristics were investigated using Kaplan-Meier survival and Cox proportional hazards methods. RESULTS: Overall incidence of LEL was 21.8% (stage 1, 60%; stage 2, 32%; and stage 3, 8%). Cumulative incidence increased with observation period: 12.9% at 1 year, 20.3% at 5 years, and 25.4% at 10 years. Age, cancer type, stage (International Federation of Gynecology and Obstetrics), body mass index, hysterectomy type, lymphocyst formation, lymph node metastasis, and chemotherapy were not associated with LEL. Multivariate analysis confirmed that removal of circumflex iliac lymph nodes (hazard ratio [HR], 4.28; 95% confidence interval [CI], 2.09-8.77; P < 0.0001), cellulitis (HR, 3.48; 95% CI, 2.03-5.98; P < 0.0001), and number of removed lymph nodes (HR, 0.99; 95% CI, 0.98-0.99; P = 0.038) were independent risk factors for LEL. CONCLUSIONS: Postoperative LEL incidence increased over time. The results of the present study showed a significant correlation with removal of circumflex iliac lymph nodes and cellulitis with the incidence of LEL. Multicenter or prospective studies are required to clarify treatment efficacies.


Subject(s)
Genital Neoplasms, Female/surgery , Lower Extremity/pathology , Lymph Node Excision/adverse effects , Lymphedema/classification , Lymphedema/epidemiology , Neoplasm Recurrence, Local/diagnosis , Adult , Aged , Female , Follow-Up Studies , Genital Neoplasms, Female/complications , Genital Neoplasms, Female/pathology , Humans , Lymph Nodes/pathology , Lymph Nodes/surgery , Lymphedema/etiology , Middle Aged , Neoplasm Staging , Prevalence , Prognosis , Retrospective Studies , Risk Factors , Young Adult
5.
Int J Gynecol Cancer ; 22(9): 1577-84, 2012 Nov.
Article in English | MEDLINE | ID: mdl-23060049

ABSTRACT

OBJECTIVE: This study aimed to determine the number of lymph nodes (LNs) removed in patients who underwent abdominal complete systematic pelvic and para-aortic lymphadenectomy and to identify factors that contribute to disparity in the number of LNs removed. METHODS: We retrospectively reviewed 260 patients with endometrial cancer and ovarian cancer between 1997 and 2011. All pelvic and para-aortic LNs were submitted as 25 separate packets. The correlations of the number of LNs with age, year of surgery, the operating surgeon, pathologist, body mass index (BMI), histology, clinical stage, operating time, blood loss, and lymph node metastasis were investigated. RESULTS: The median number of LNs removed was 45 pelvic (17-92) and 25 para-aortic (6-69) LNs. Among pelvic LNs, the common iliac nodes were the most frequently removed followed by the obturator nodes. The median number of the left upper para-aortic LNs between the left renal vein and the inferior mesenteric artery was highest among para-aortic LNs. There were significant correlations between the total number of LNs removed and age (P = 0.036), histology (clear vs serous; P = 0.015), and BMI (P < 0.0001) in ovarian cancer. Features associated with higher LN count on multivariate linear regression analysis included younger patients (P = 0.038) and higher BMI (P = 0.012). CONCLUSIONS: Age and BMI are independently associated with higher LN counts during LN dissection in ovarian cancer. The present study results may be important when using LN counts as a surrogate for adequate lymphadenectomy.


Subject(s)
Carcinoma, Endometrioid/surgery , Endometrial Neoplasms/surgery , Lymph Node Excision/methods , Lymph Nodes/pathology , Ovarian Neoplasms/surgery , Adenocarcinoma, Mucinous/epidemiology , Adenocarcinoma, Mucinous/pathology , Adenocarcinoma, Mucinous/surgery , Adult , Aged , Aorta/pathology , Aorta/surgery , Carcinoma, Endometrioid/epidemiology , Carcinoma, Endometrioid/pathology , Cohort Studies , Endometrial Neoplasms/epidemiology , Endometrial Neoplasms/pathology , Female , Humans , Lymph Node Excision/statistics & numerical data , Lymph Nodes/surgery , Lymphatic Metastasis , Middle Aged , Ovarian Neoplasms/epidemiology , Ovarian Neoplasms/pathology , Pelvis/pathology , Pelvis/surgery , Young Adult
6.
Ann Surg Oncol ; 19(1): 268-73, 2012 Jan.
Article in English | MEDLINE | ID: mdl-21717243

ABSTRACT

BACKGROUND: Lower extremity lymphedema (LEL) is a serious complication caused by lymphadenectomy in patients with gynecologic malignancies. In this study, we evaluated the effect of preserving the circumflex iliac lymph nodes (CILNs), i.e., the most caudal external iliac lymph nodes, for the prevention and reduction of LEL by comparing two groups of patients, one in which CILN were removed and the other in which CILNs were preserved. METHODS: We retrospectively reviewed 329 patients with gynecologic malignancies who had undergone abdominal complete systematic pelvic and para-aortic lymphadenectomy. The patients were divided into nonpreserved (n = 189) and preserved (n = 140) groups, depending on whether CILNs were removed. Primary outcome measures included the incidence and severity of LEL. RESULTS: The incidence of LEL was significantly lower in the preserved group than in the nonpreserved group (P < 0.0001). The frequency of LEL was also significantly lower in the preserved group than in the nonpreserved group regardless of the range of pelvic and para-aortic lymphadenectomy (P < 0.0001). LEL in the overwhelming majority of cases in the preserved group was mild, and no patients experienced severe LEL. Further, the incidence of cellulitis was 0% in the preserved group, while it was 12.7% in the nonpreserved group (P < 0.0001). Lymphoscintigraphy revealed collateral pathways from the preserved CILN along the iliac and large abdominal vessels. CONCLUSIONS: This method of lymph node preservation is a simple and extremely effective approach for preventing/reducing LEL after pelvic and para-aortic lymphadenectomy for patients with gynecologic malignancies.


Subject(s)
Genital Neoplasms, Female/surgery , Lower Extremity , Lymph Node Excision , Lymphedema/prevention & control , Pelvis/surgery , Adult , Aged , Female , Genital Neoplasms, Female/pathology , Humans , Lymphoscintigraphy , Middle Aged , Pelvis/pathology , Prognosis , Retrospective Studies , Young Adult
7.
Acta Obstet Gynecol Scand ; 90(12): 1434-9, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21854366

ABSTRACT

OBJECTIVE: To examine the association between maternal weight gain and twin-twin transfusion syndrome (TTTS). DESIGN: Retrospective observational study in two tertiary care centers. POPULATION: All 124 women with monochorionic diamniotic twin pregnancies who gave birth at ≥ 16 gestational weeks between 2002 and 2010. METHODS: Analysis of chronological relation between maternal weight gain per week (weekly gain) and the diagnosis of TTTS. MAIN OUTCOME MEASURE: Sonographic diagnosis of TTTS. RESULTS: A weekly weight gain ≥ 1.4 kg occurred in 45 women, preceded the diagnosis of TTTS in 22 (78.6%) of the 28 women with TTTS, and was associated with TTTS [women with one weekly weight gain ≥ 1.4 kg vs. women with no weekly weight gains ≥1.4 kg who were diagnosed as having TTTS: 48.9% (22/45) vs. 7.6% (6/79); RR, 6.44; 95%CI, 2.82-14.69]. At given gestational weeks between 16 and 27, the mean (± SD) prospective risk of the development of TTTS within three weeks was 52.0 ± 33.8% among women who showed a weekly weight gain ≥ 1.4 kg for the first time, whereas the risk of the development of TTTS within one week was 1.6 ± 1.7% among women who never showed a weekly weight gain ≥ 1.4 kg. CONCLUSIONS: Excessive maternal weight gain ≥ 1.4 kg/week is likely to occur during the development of TTTS.


Subject(s)
Fetofetal Transfusion/diagnosis , Pregnancy Complications/diagnosis , Weight Gain , Adult , Female , Fetofetal Transfusion/complications , Fetofetal Transfusion/diagnostic imaging , Humans , Polyhydramnios/diagnosis , Polyhydramnios/etiology , Pregnancy , Pregnancy Complications/diagnostic imaging , ROC Curve , Retrospective Studies , Risk Assessment , Ultrasonography
8.
J Clin Anesth ; 23(2): 113-8, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21377074

ABSTRACT

STUDY OBJECTIVE: To investigate the effect of small-dose ketamine on the predicted effect-site concentration of propofol required for loss of consciousness (LOC) and Laryngeal Mask Airway (LMA) insertion. DESIGN: Randomized, double-blinded study. SETTINGS: Operating room. PATIENTS: 50 ASA physical status 1 and 2 women scheduled for elective breast or gynecological surgery. INTERVENTIONS: Patients were randomly allocated to a ketamine group or a control group. Thirty seconds before propofol injection, ketamine group patients received ketamine 0.2 mg/kg, while control group patients received saline. Propofol was given in a target-controlled infusion and target blood concentration was gradually increased until LOC. The effect-site concentrations for attempting LMA insertion was predetermined by modifying Dixon's up and down method. LMA insertion was attempted without muscular blocking agents. MEASUREMENTS: Pain scores on propofol injection, effect-site concentrations at LOC, hemodynamic variables, and patient movement or side effects on LMA insertion were recorded. MAIN RESULTS: The effect-site concentration of propofol required for LOC was 2.14 µg/mL for the control group and 1.66 for the ketamine group (P = 0.0082). The predicted effect-site concentration of propofol alone at which 50% of patients did not move with LMA insertion (EC(50)LMI) was 3.59 µg/mL (95% CI: 3.18 ∼ 4.19 µg/mL). Pretreatment with ketamine 0.2 mg/kg decreased EC(50)LMI from 3.59 (3.18 ∼ 4.19) to 2.39 (1.22 ∼ 2.99). CONCLUSIONS: Pretreatment with ketamine 0.2 mg/kg reduced the propofol concentration required for both LOC (22%) and LMA insertion (33%) in women.


Subject(s)
Anesthetics, Dissociative/therapeutic use , Anesthetics, Intravenous/pharmacokinetics , Ketamine/therapeutic use , Propofol/pharmacokinetics , Adult , Aged , Anesthetics, Dissociative/administration & dosage , Anesthetics, Intravenous/administration & dosage , Breast Neoplasms/surgery , Double-Blind Method , Female , Gynecologic Surgical Procedures/methods , Humans , Ketamine/administration & dosage , Laryngeal Masks , Middle Aged , Propofol/administration & dosage
9.
Congenit Anom (Kyoto) ; 49(2): 61-5, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19489956

ABSTRACT

Cytogenetic amniocentesis (CA) has been performed as a reliable prenatal diagnostic method for decades. The aims of the present study were to reveal the frequency of fetal chromosome abnormalities according to medical indications of CA, and to assess the risks of specific abnormal ultrasound findings. Data on chromosome karyotypes of fetuses from 5043 Japanese mothers were collected. Group I comprised 4626 fetuses whose mothers underwent CA due to a variety of parental reasons. Group II comprised 417 fetuses whose mothers underwent CA due to fetal abnormality, abnormality of amniotic fluid volume and fetal growth restriction. The frequency of chromosome abnormalities in Group II (17.7%) was significantly higher than in Group I (1.8%). The frequencies of chromosome abnormalities in Group II singleton fetuses with fetal abnormality, polyhydramnios and fetal growth restriction were 21.5, 22.9 and 19.6%, respectively. By multivariate analyses, we found that cystic hygroma (odds ratio 5.6, 95% CI 2.7-11.6), abnormal extremity (5.0, 1.7-14.4) and cardiovascular abnormality (3.3, 1.1-10.1) were significant variants associated with fetal chromosomal abnormalities. Information revealed in the present study constitutes a beneficial reference for genetic counseling.


Subject(s)
Chromosome Aberrations , Fetal Diseases/diagnostic imaging , Adult , Amniocentesis , Chromosome Disorders , Female , Humans , Karyotyping , Pregnancy , Pregnancy Complications/diagnosis , Ultrasonography
10.
Am J Obstet Gynecol ; 200(6): 663.e1-11, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19371854

ABSTRACT

OBJECTIVE: The purpose of this study was to analyze the effects of intrauterine inflammation on cerebral hemodynamics and white-matter injury in premature fetal sheep. STUDY DESIGN: Fetuses were given an intravenous infusion of granulocyte colony-stimulating factor and an intraamniotic infusion of endotoxin; the fetuses were then assigned randomly to an acute hemorrhage group, an exchange transfusion group, or a control group. During each insult, the cerebral hemodynamics were assessed with near-infrared spectroscopy. Finally, the fetuses were processed for neuropathologic analysis and compared statistically. RESULTS: Necrotizing funisitis and chorioamnionitis were induced in all the fetuses. A significant decrease in the blood oxygen content and an increase in the brain total hemoglobin level were observed after the endotoxin infusion. Soon after hemodynamic insult, the fetuses in both the acute hemorrhage and the exchange transfusion groups showed an abrupt decrease in the total brain hemoglobin level; 4 of the 5 fetuses in each treatment group, but none of the fetuses in the control group, exhibited periventricular leukomalacia. CONCLUSION: Hemorrhagic hypotension or anemic hypoxemia might induce a sudden cessation of fetal brain-sparing effects through progressive inflammatory hypoxemia, which results in focal white-matter injuries.


Subject(s)
Brain Diseases/etiology , Brain Diseases/physiopathology , Cerebrovascular Circulation , Fetal Diseases/etiology , Fetal Diseases/physiopathology , Fetus/physiopathology , Hemodynamics , Inflammation/complications , Animals , Sheep
11.
Pediatr Res ; 62(6): 670-3, 2007 Dec.
Article in English | MEDLINE | ID: mdl-17957156

ABSTRACT

The purpose of the present study was to determine whether experimental intrauterine inflammation could induce necrotizing funisitis, a severe, chronic inflammation of the umbilical cord. Fetuses, randomly divided into four groups (n = 4 each), were infused with 50 mug/d of granulocyte-colony stimulating factor (G-CSF) intravenously on d 125-129 of gestation (G-CSF group), 20 mg of endotoxin into the amniotic cavity on d 127 gestation (endotoxin group), both G-CSF and endotoxin (G-CSF + endotoxin group), or only saline (control group). On d 130 of gestation, the umbilical cords were processed for histologic analysis, scored for degree of inflammation, and compared statistically. At birth, the blood polymorphonuclear leukocyte counts in G-CSF and G-CSF + endotoxin groups were significantly higher than those in endotoxin and control groups (p < 0.05). The inflammatory score of the umbilical cord in G-CSF + endotoxin group was significantly higher than those in the other three groups (p < 0.05). All the fetuses in G-CSF + endotoxin group had necrotizing funisitis, but none of the fetuses in the other three groups developed this condition. An increase in blood polymorphonuclear leukocytes before their activation in the umbilical cord is probably essential for experimentally inducing necrotizing funisitis.


Subject(s)
Chorioamnionitis/pathology , Fetus/pathology , Neutrophil Infiltration , Neutrophils/pathology , Premature Birth , Animals , Animals, Newborn , Cesarean Section , Chorioamnionitis/blood , Chorioamnionitis/chemically induced , Disease Models, Animal , Female , Fetal Blood/cytology , Gestational Age , Granulocyte Colony-Stimulating Factor/administration & dosage , Infusions, Intravenous , Leukocyte Count , Lipopolysaccharides/administration & dosage , Necrosis , Pregnancy , Sheep , Umbilical Cord/pathology
14.
Am J Obstet Gynecol ; 194(4): 1057-63, 2006 Apr.
Article in English | MEDLINE | ID: mdl-16580296

ABSTRACT

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.


Subject(s)
Brain Ischemia/physiopathology , Cerebrovascular Circulation , Fetal Diseases/physiopathology , Hemodynamics , Leukomalacia, Periventricular/physiopathology , Animals , Animals, Newborn , Female , Fetal Diseases/etiology , Fetal Diseases/metabolism , Hemoglobins/metabolism , Hemorrhage , Humans , Hypotension , Infant, Newborn , Leukomalacia, Periventricular/etiology , Leukomalacia, Periventricular/metabolism , Oxygen/metabolism , Pregnancy , Sheep , Spectroscopy, Near-Infrared
15.
Clin Pharmacol Ther ; 78(6): 647-55, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16338280

ABSTRACT

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.


Subject(s)
Anesthesia Recovery Period , Aryl Hydrocarbon Hydroxylases/genetics , Diazepam/pharmacokinetics , Mixed Function Oxygenases/genetics , Actins/genetics , Actins/metabolism , Adult , Anesthesia, General/methods , Area Under Curve , Aryl Hydrocarbon Hydroxylases/metabolism , Cytochrome P-450 CYP2C19 , Cytochrome P-450 CYP3A , Cytochrome P-450 Enzyme System/genetics , Cytochrome P-450 Enzyme System/metabolism , Diazepam/administration & dosage , Diazepam/blood , Female , Genotype , Humans , Hypnotics and Sedatives/administration & dosage , Hypnotics and Sedatives/blood , Hypnotics and Sedatives/pharmacokinetics , Male , Middle Aged , Mixed Function Oxygenases/metabolism , Polymorphism, Genetic , Prospective Studies , RNA, Messenger/genetics , RNA, Messenger/metabolism , Time Factors
17.
BJOG ; 112(1): 69-74, 2005 Jan.
Article in English | MEDLINE | ID: mdl-15663400

ABSTRACT

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.


Subject(s)
Acetamides/adverse effects , Adrenergic beta-2 Receptor Agonists , Adrenergic beta-Agonists/adverse effects , Cardiovascular System/drug effects , Fetus/drug effects , Naphthalenes/adverse effects , Respiratory System/drug effects , Tocolytic Agents/adverse effects , Acetamides/administration & dosage , Adrenergic beta-Agonists/administration & dosage , Analysis of Variance , Animals , Blood Glucose/metabolism , Blood Pressure/drug effects , Female , Fetus/metabolism , Heart Rate/drug effects , Infusions, Intravenous , Insulin/metabolism , Lactates/metabolism , Naphthalenes/administration & dosage , Potassium/metabolism , Pregnancy , Sheep , Tocolytic Agents/administration & dosage
18.
J Pediatr Surg ; 39(7): 1055-8, 2004 Jul.
Article in English | MEDLINE | ID: mdl-15213898

ABSTRACT

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.


Subject(s)
Choledochal Cyst/diagnostic imaging , Choledochal Cyst/surgery , Fetal Diseases/diagnostic imaging , Fetal Diseases/surgery , Anastomosis, Surgical/methods , Biopsy , Choledochal Cyst/embryology , Follow-Up Studies , Humans , Infant , Infant, Newborn , Liver/pathology , Ultrasonography, Prenatal
19.
Nihon Rinsho ; 62(2): 373-8, 2004 Feb.
Article in Japanese | MEDLINE | ID: mdl-14968548

ABSTRACT

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.


Subject(s)
Urogenital Abnormalities , Female , Humans , Infant, Newborn , Male , Urogenital Abnormalities/diagnosis , Urogenital Abnormalities/etiology , Urogenital Abnormalities/pathology , Urogenital Abnormalities/surgery
20.
Congenit Anom (Kyoto) ; 43(1): 72-8, 2003 Mar.
Article in English | MEDLINE | ID: mdl-12692406

ABSTRACT

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.


Subject(s)
Cystic Adenomatoid Malformation of Lung, Congenital/diagnosis , Cystic Adenomatoid Malformation of Lung, Congenital/genetics , Prenatal Diagnosis , Adult , Cystic Adenomatoid Malformation of Lung, Congenital/diagnostic imaging , Cystic Adenomatoid Malformation of Lung, Congenital/therapy , Female , Fetal Diseases , Humans , Infant, Newborn , Lung/abnormalities , Lung Diseases/therapy , Magnetic Resonance Imaging , Male , Pregnancy , Prenatal Care , Time Factors , Ultrasonography
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