Down-Regulation of Survivin by Nemadipine-A Sensitizes Cancer Cells to TRAIL-Induced Apoptosis

The tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the tumor necrosis factor family of cytokines. TRAIL selectively induces apoptotic cell death in various tumors and cancer cells, but it has little or no toxicity in normal cells. Agonism of TRAIL receptors has been considered to be a valuable cancer-therapeutic strategy. However, more than 85% of primary tumors are resistant to TRAIL, emphasizing the importance of investigating how to overcome TRAIL resistance. In this report, we have found that nemadipine-A, a cell-permeable L-type calcium channel inhibitor, sensitizes TRAIL-resistant cancer cells to this ligand. Combination treatments using TRAIL with nemadipine-A synergistically induced both the caspase cascade and apoptotic cell death, which were blocked by a pan caspase inhibitor (zVAD) but not by autophagy or a necrosis inhibitor. We further found that nemadipine-A, either alone or in combination with TRAIL, notably reduced the expression of survivin, an inhibitor of the apoptosis protein (IAP) family of proteins. Depletion of survivin by small RNA interference (siRNA) resulted in increased cell death and caspase activation by TRAIL treatment. These results suggest that nemadipine-A potentiates TRAIL-induced apoptosis by down-regulation of survivin expression in TRAIL resistant cells. Thus, combination of TRAIL with nemadipine-A may serve a new therapeutic scheme for the treatment of TRAIL resistant cancer cells, suggesting that a detailed study of this combination would be useful.

Increased sFlt-1 to PlGF Ratio in Women Who Subsequently Develop Preeclampsia

The purpose of this study was to determine whether the levels of soluble fms-like tyrosine kinase-1 (sFlt-1) and placenta growth factor (PlGF) are altered during the second trimester in the plasma of women who subsequently develop preeclampsia. We performed a case-control study to compare the levels of sFlt-1 and PlGF in the preeclamptic (n=46) and normal pregnant women (n=100). The maternal plasma levels of sFlt-1 and PlGF were measured by enzyme-linked immunosorbent assay. The sFlt-1 levels were significantly higher in the preeclamptic women than in normal controls (p<0.001), while the PlGF levels were significantly lower (p<0.001). In normal controls, sFlt-1 levels were positively correlated (r=0.27, p=0.008), whereas, in the preeclamptic women, those were negatively correlated with the PlGF levels (r=-0.423, p=0.005). Furthermore, the log[sFlt-1/PlGF] ratio was significantly higher in the preeclamptic women than in normal controls (p<0.001). The receiver operating characteristic curve revealed a specificity of 78% with a diagnostic sensitivity of 80.4%; the optimal cut-off value of the log[sFlt-1/PlGF] ratio was 1.4 (95% CI 0.756-0.910, p<0.001). Preeclampsia showed a strong association with increased levels of sFlt-1 and decreased levels of PlGF in the second trimester maternal plasma. Accordingly, the sFlt-1/PlGF ratio may provide early prediction of subsequent development of preeclampsia.

Threshold of Nuchal Translucency for the Detection of Chromosomal Aberration: Comparison of Different Cut-offs

This study evaluated the sensitivities and false positive rates of the screening test using ultrasonographic measurement of thickness of nuchal translucency (NT) with different cut-offs for chromosomal aberration in a Korean population. We included 2,570 singleton pregnancies undergoing ultrasound between 11 weeks and 14 weeks of gestation in this study. We analyzed the sensitivities of NT alone for screening chromosomal aberration using three cut-offs -2.5 mm, 3.0 mm, and 95th percentile for each crown rump length (CRL). There were 31 chromosomal aberrations (1.2%) including 12 cases of trisomy 21. The numbers of chromosomal aberrations that were detected by NT with different cut-offs of 2.5 mm, 3.0 mm and the 95th percentile CRL were 22, 18 and 23, respectively. At a threshold of 2.5 mm, the sensitivity and the false positive rate for total chromosomal aberrations were 67.7% and 6.3%, respectively. At 3.0 mm, those were 54.8% and 3.5%, respectively. At the 95th percentile CRL, those were 70.9% and 5.8%, respectively. The use of CRL-dependent cut-offs for nuchal translucency improves the detection of chromosomal aberrations when compared to fixed cut-offs in a Korean population.

Perinatal Outcome in Twin Pregnancies Complicated by Gestational Diabetes Mellitus: A Comparative Study

The purpose of this study is to compare perinatal outcomes of twin pregnancies complicated by gestational diabetes (GDM) with those unaffected by GDM. A total of 1,154 twin pregnancies who delivered at Cheil General Hospital, between January 1998 and December 2002 were recruited to participate in a retrospective analysis. Out of these twin pregnancies, 37 women were had GDM. Four pregnancies exposed to GDM were excluded due to the loss of medical records; therefore 33 twin pregnancies exposed to GDM were enrolled. We matched the GDM pregnancies with pregnancies unaffected by GDM in a 1:2 ratio; therefore there were 33 GDM/66 without GDM who delivered during the study period. Our findings show that there were no significant differences including birth weight, Apgar score, respiratory distress syndrome, meconium aspiration pneumonia, transient tachypnea of new born, hyperbilirubinemia, hypoglycemia, hypocalcemia and congenital anomalies. Therefore, well controlled GDM may not increase perinatal complications in twin pregnancies. Careful pregnancy management and fetal surveillance in twin pregnancies is important to decrease perinatal complications and maintain a sound pregnancy and healthy offspring.

Ultrasound Screening for Fetal Down Syndrome in the Second Trimester of Pregnancy / 대한산부인과학회잡지

OBJECTIVE: To determine the risk of Down syndrome in fetuses with sonographic markers using the likelihood ratios and individual risk assessment. METHODS: We retrospectively evaluated the midtrimester genetic sonographic features of fetuses with Down syndrome and compared them with euploid fetuses. Patients were referred for an increased risk of aneuploidy and evaluated for the presence of structural defects, a nuchal fold, short long bones, pyelectasis, brachycephaly, small stomach, and hyperechoic bowel. Outcome information included the results of genetic amniocentesis (if performed), the results of pediatric assessment, and follow-up after birth. The sensitivity, specificity, and likelihood ratios for markers ware calculated isolated findings. RESULTS: There were 59 fetuses with Down syndrome and 600 euploid fetuses. The presence of any marker resulted in sensitivity for the detection of Down syndrome of 86.4% with a false-positive rate of 13.6%. Structural defect had a likelihood ratio of 77.8. As an isolated marker, the nuchal fold, short humerus, short femur, echogenic bowel and renal pyelectasia has a likelihood ratio of 20.2, 12.7, 3.9, 2.5, 1.1 respectively. Other isolated markers had low likelihood ratios because of the higher prevalence in the unaffected population. CONCLUSION: Combining second-trimester serum testing and fetal sonography is a feasible approach to Down syndrome screening, compatible with current obstetric practice. Although an isolated marker with a low likelihood ratio may not increase a patient's risk of Down syndrome, the presence of such a marker precludes reducing the risk of aneuploidy. This information will be useful in counseling pregnant women who are at high risk for fetal Down syndrome and who prefer to undergo genetic sonography before deciding about genetic amniocentesis.

Ultrasound Screening for Fetal Down Syndrome in the Second Trimester of Pregnancy / 대한산부인과학회잡지

OBJECTIVE: To determine the risk of Down syndrome in fetuses with sonographic markers using the likelihood ratios and individual risk assessment. METHODS: We retrospectively evaluated the midtrimester genetic sonographic features of fetuses with Down syndrome and compared them with euploid fetuses. Patients were referred for an increased risk of aneuploidy and evaluated for the presence of structural defects, a nuchal fold, short long bones, pyelectasis, brachycephaly, small stomach, and hyperechoic bowel. Outcome information included the results of genetic amniocentesis (if performed), the results of pediatric assessment, and follow-up after birth. The sensitivity, specificity, and likelihood ratios for markers ware calculated isolated findings. RESULTS: There were 59 fetuses with Down syndrome and 600 euploid fetuses. The presence of any marker resulted in sensitivity for the detection of Down syndrome of 86.4% with a false-positive rate of 13.6%. Structural defect had a likelihood ratio of 77.8. As an isolated marker, the nuchal fold, short humerus, short femur, echogenic bowel and renal pyelectasia has a likelihood ratio of 20.2, 12.7, 3.9, 2.5, 1.1 respectively. Other isolated markers had low likelihood ratios because of the higher prevalence in the unaffected population. CONCLUSION: Combining second-trimester serum testing and fetal sonography is a feasible approach to Down syndrome screening, compatible with current obstetric practice. Although an isolated marker with a low likelihood ratio may not increase a patient's risk of Down syndrome, the presence of such a marker precludes reducing the risk of aneuploidy. This information will be useful in counseling pregnant women who are at high risk for fetal Down syndrome and who prefer to undergo genetic sonography before deciding about genetic amniocentesis.

The Influence of Monochorionicity on the Perinatal Outcomes in Spontaneously Conceived Twins / 대한산부인과학회잡지

OBJECTIVE: The Purpose of this study was to evaluate monochorionicity as a risk factor for adverse perinatal outcomes in spontaneously conceived twins. METHODS: Using an established database, the study included pregnant women with spontaneously conceived twin gestations between January 1998 and December 2002. From a total of 1145 twin deliveries, 371 spontaneous twin pregnancies were observed in Department of Obstetrics and Gynecology in Samsung Cheil Hospital and Women's Healthcare Center. Chorionicity was established by histologic examination and divided into two groups, monochorionic (diamnionic and monoamnionic) twins (MC) and dichorionic diamnionic twins (DC). The obstetric and neonatal outcomes were compared between the two groups. RESULTS: There were 176 MC and 195 DC twin deliveries following natural fertilization. The incidence of intrauterine growth restriction was significantly higher (16.4% vs. 5.4%, P<.001) in MC twins. However, there were no statistically significant differences in the frequency of antepartum or intrapartum complications such as preterm delivery, preeclampsia, placenta previa and gestational diabetes mellitus between the two groups. In addition, there were no statistically significant difference in the frequency of neonatal complications, congenital anomalies, Apgar scores, perinatal mortality, morbidity and duration of neonatal intensive care unit admission. CONCLUSION: When compared with DC twin group, MC twin group is more likely to have a higher incidence of intrauterine growth restriction in natural fertilization. However, monochorionicity is not a risk factor for adverse obstetric outcomes, perinatal mortality and morbidity in spontaneously conceived twins in our study.

The Distribution of Fetal Nuchal Translucency Thickness in Normal Korean Fetuses

The aim of present study was to establish normative data for the distribution of nuchal translucency (NT) thickness in normal Korean fetuses. The data were collected from pregnant women with singleton pregnancies in whom fetal ultrasound was performed and the fetal NT thickness was measured between 11 and 14 weeks of gestation. Among them, a total of 2,577 fetuses with a known normal outcome were included in this study. The distribution of multiple of median (MoM) values of the NT thickness with crown-rump length (CRL) in 10-mm intervals and the 95th percentile of MoM were calculated with the linear regression method. The present study showed that NT measurements increase with increasing CRL and a false positive rate increases with increasing gestational age. Therefore, a fixed cut-off point through the first trimester was not appropriate and each NT measurement should be examined according to the gestational age. The present study offers normative data of the fetal NT thickness in a Korean population, which can be used as reference for screening chromosomal aberrations or other congenital abnormalities in the first trimester.

Maternal Exposure to Environmental Tobacco Smoke (ETS) and Pregnancy Outcome (low birth weight or preterm baby) in Prospective Cohort Study / 예방의학회지

OBJECTIVES: This study was performed to examine the relationship between maternal exposure to environmental tobacco smoke (ETS) and pregnancy outcomes (low birth weight or preterm baby) in a prospective cohort study. METHODS: We made a pregnant women's cohort, and followed the pregnancy outcomes, between May 1st 2001 and August 31st 2002. We surveyed 2, 250 women who visited our hospital during their 35th gestational week, with a self-administered questionnaire. The final total of mother-infant pairs analyzed in this study was 1, 712. We used a multiple logistic regression analysis to analyze the effect of maternal ETS on the incidence of preterm or low birth weight, and a linear regression analysis for the birth weight and gestational age. RESULTS: Higher exposure to ETS (> or =1 hours/day) during pregnancy was more negatively associated with the gestational age and birth weight, than no exposure to ETS (no or less than 1hour). Maternal exposure to ETS was associated with preterm baby (adjusted odds ratio (AOR) 1.7; 95% confidence interval (CI) 0.9, 3.3) and low birth weight (AOR 2.3; 95% CI 0.9, 5.5). In addition, we found that maternal ETS may reduce the birth weight by 70g after adjusting for potential confounding factors. CONCLUSIONS: This study suggests that maternal exposure to ETS during pregnancy may increase the frequency of low birth weights and preterm births.

Pregnancy Outcome after Exposure of Suspected Teratogens in Early Pregnancy / 대한산부인과학회잡지

OBJECTIVE: To compare the risk of congenital anomaly after exposure to suspected teratogens in early pregnancy with the known baseline risk to the geneneral population. METHODS: From September 1999 to August 2001, we counseled about the teratogenic risk of the fetus by relevant medical literatures after assessment of type, amount, and time of exposure for 302 pregnant women exposed to suspected teratogens such as drugs, radiation, alcohol, and cigarette smoking. We followed up on the pregnancy outcome with the rate of termination of pregnancy and incidence of congenital anomaly. RESULTS: Among a total of 302 cases, 253 pregnant women (83.8%) delivered, 15 (5%) were aborted spontaneously, 34 (11.3%) were terminated. 297 pregnant women (98.3%) were lastly exposed to drugs in mean 5.3 +/- 0.2 gestational weeks. Medicines taken were gastrointestinal drugs (23%), NSAIDs (18.3%), antibiotics (16.2%), antihistamines (10.8%) in the order of frequency. 74 pregnant women (24.5%) were exposed to radiation in mean 5.1 +/- 0.5 gestational weeks. The mean dose was 234.60 mrem. 113 pregnant women (37.3%) lastly drank alcohol in mean 4.5 +/- 0.4 gestational weeks and the mean amount was 1.55 oz. 36 pregnant women (11.9%) lastly smoked in mean 4.4 +/- 0.3 gestational weeks and the mean amount was 7.3 cigarettes/day. We found structural anomalies in 5 cases (Polydactylyl, Ileal agenesis, Both ear mass, Left ectopic kidney, Meningomyelocele) and 1 chromosomal abnormality case (Trisomy18). CONCLUSION: The rate of fetal structural anomaly was 2% in this study and is not more than baseline risk of general population. Therefore, evidence-based teratogenic risk counseling may prevent unnecessary pregnancy termination.

Clinical Outcomes of Increased Nuchal Translucency in Three Years / 대한산부인과학회잡지

OBJECTIVE: To evaluate the relationship between increased nuchal translucency (NT) and abnormal pregnancy outcomes. METHODS: From January 1999 to December 2001, The 298 fetuses of increased nuchal translucency (>or=2.5 mm) in period of 10-14 weeks gestation were reviewed retrospectively. Amniocentesis and high resolution ultrasonography during second trimester were done for all cases. We analyzed septation within NT, karyotypes, structural anomalies, and adverse pregnancy outcomes such as spontaneous abortion, intrauterine fetal death and preterm delivery. RESULTS: The mean age of the patients was 30.5 +/- 3.5 years. The mean gestational age and CRL were 12.5 +/- 0.95 weeks and 6.5 +/- 1.15 mm. We observed 18 (6%) cases of abnormal karyotypes. 7/46 (15.2%) fetuses with internal septation had abnormal karyotype and 11/252 (4.4%) fetuses without internal septation had abnormal karyotype (p=0.013). Among the 280 fetuses with normal karyotype, 8 (2.8%) fetuses had structural anomalies and 18 (6.4%) fetuses had adverse pregnancy outcomes. The chromosomal abnormality and structural anomaly were significantly increased in the group of nuchal translucency thickness above 3.5 mm (p=0.001). CONCLUSION: Increased nuchal translucency is related with chromosomal abnormality and abnormal pregnancy outcomes.

The Rate of Planned Pregnancy and Associated Factors Related to Planned Pregnancy / 대한산부인과학회잡지

OBJECTIVE: To evaluate planned pregnancy rate and associated factors related planned pregnancy. METHODS: We surveyed 1,396 cases from May 2002 to December 2002. The cases were derived from the Maternity school. They filled out questionnaire including planned pregnancy, medico-social-economic status. Then, we assessed the planned pregnancy rate with associated medico-social-economic state, through the prospective study. RESULTS: The planned pregnancy rate is 51.4%. The major factor which affected the planned pregnancy rate is the income of the family. The association with the planned pregnancy rate and the parity, age, and educational attainment of the women are not statistically significant. In unplanned group, exposure to alcohol, X-ray and medication is significantly increased in early pregnancy. CONCLUSION: The planned pregnancy can prevent induced abortion and reduce the birth defects due to early exposure to teratogen. Therefore it is important to make an effort to raise the planned pregnancy rate.

Evaluation of Insulin-like Growth Factor-binding Protein-1 in Cervical Secreation as a Predictor of Preterm Delivery / 대한산부인과학회잡지

OBJECTIVE: This study is performed to assess whether detection of phosphorylated insulin like growth factor binding protein-1 (phIGFBP-1) in cervical secretions by a bed side test could be used to prediction preterm delivery in patient with regular uterine contraction. METHODS: In our prospective study, 42 women between 20.2 and 36.4 weeks gestation with regular, persistent contraction (2-3/min for 30 min). and 27 women between 22.0 and 37.0 weeks of gestation without symptoms of preterm labor were assessed for presence of cervical phIGFBP-1. Dacron swabs were applied to the cervix and assayed in 5min by using immunochromatography, actim partus test (Medix Biochemica). RESULTS: Of the 42 patients with regular uterine contractions, 22 had a positive actim partus test and 20 had a negative test. Among the 22 patients with positive test, 5 delivered preterm and other 17 patients delivered term (<37 weeks). Among the the 20 women with a negative test, 2 delivered preterm (NS). The mean concentration of phIGFBP-1 in 22 positive patients is 83.8+/-86.5 microgram/L and that in 20 negative patients is 2.1+/-5.0 microgram/L (P<0.0001) (Table 4). Sensitivity, specificity, false positive, false negative, positive predictive, and negative predictive values were 18.5, 59.6, 40.3, 28.6, 16.7, and 94.9%, respectively. CONCLUSION: The absence of cervical phIGFBP-1 is seems to be a valuable test in excluding preterm delivery in patients who have regular uterine contractions. The high negative predictive value in this study may enable physicians to prevent over treatment of patients with uterine contractions. Therefore, many unwanted side-effects and complications of potentially hazardous tocolytic therapy can be prevented.

Clinical Analysis on Emergency Postpartum Hysterectomy / 대한주산의학회잡지

OBJECTIVE: To analyze incidence, indications, risk factors, complications, and neonatal outcomes of emergency postpartum hysterectomies performed at EulJi University Medical Center. METHODS: A retrospective study of all cases of postpartum hysterectomies between May. 1996 and Dec. 2000. was carried out. RESULTS: 37 cases of postpartum hysterectomies during this period were performed, for overall incidnce of 2.3 per 1000 deliveries. Incidence after vaginal delivery and cesarean section was 0.03% and 0.52% respectively. The rate of postpartum hysterectomy increased with increasing age and parity. The main indications were placental disorders(54.1%) including placenta previa and adherent placenta, uterine atony(37.8%), uterine myoma(5.4%) and uterine rupture(2.7%) in order. The relative risk of postpartum hysterectomy according to the risk factors was 97.6(95% confidence interval 52.17-184.06) for placental disorders, 16.3(95% confidence interval 4.94-52.31) for cesarean section and 2.4(95% confidence interval 1.21-4.76) for previous cesarean section. The mean amount of transfuion was 17.1 pints. Although no maternal mortality had occurred, 16 patients(43.2%) had complica-ions including respiratory complication(13.5%), hemorrhagic complication(10.8%), infection(8.1%) and urologic injury(8.1%). Regarding fetal outcome, 2 of 38 infants(1 case, twin) were stillborn (5.3%) and 10 infants(26.3%) were suffered from various illness including prematurity, sepsis, meningitis, and brain hemorrhage. CONCLUSION: The data identifies placental disorders are the leading cause of postpartum hysterectomy. Although postpartum hysterectomy is a necessary life-saving operation, maternal morbidity remained high.

Clinical Study of Peripartum Cardiomyopathy / 대한주산의학회잡지

No abstract available.

Insulin-like Growth Factor-Binding Protein-1 in Cervical Secretion as a Predictor of Preterm Delivery / 대한산부인과학회잡지

OBJECTIVE: The phosphorylated isoforms of insulin-like growth factor-binding protein-1 (IGFBP-1) were produced by the decidua. The aim of this study was to evaluate whether the presence of phosphorylated IGFBP-1 (phIGFBP-1) in cervical secretions of pregnant women with preterm uterine contractions can predict an increased risk of preterm delivery and infectious complications. METHOD: The prospective study of 32 pregnant women who admitted under the diagnosis of preterm labor with intact membrane at gestational age of 24+0 to 36+0 weeks. Phsphorylated IGFBP-1 was qualitatively assayed using immunochromatography in cervical swab samples at the time of admission. The interval between the test and delivery, gestational age, duration of tocolysis, birth weight, CRP, ESR and the presence of neonatal infection were compared between positive and negative groups. RESULTS: There was no differnce in age, obstetric histories and gestational age and Bishop score at the time of admission between two groups. Eight pregnacies out of 13 positive group and two pregnacies out of 19 negative group resulted in preterm birth. The sensitivity and specificity of the phIGFBP-1 test to predict preterm birth were 80.0% and 77.3%, respectively. The mean getational age and interval between the test and delivery were 38.36 weeks and 45.0 days and 35.78 weeks and 35.46 days in negative and positive group respectively. The birth weight of the babies was significantly higher in negative group. The duration of tocolysis was longer in positive group with marginal statistical significance. The CRP, ESR and WBC count were not different. One postpartum sepsis, one neonatal death and one necrotizing enterocolitis were complicated in positive group. CONCLUSION: The presence of phIGFBP-1 is an usful marker to predict preterm birth in case of regular uterine contraction with intact fetal membranes.

Insulin-like Growth Factor-Binding Protein-1 in Cervical Secretion as a Predictor of Preterm Delivery / 대한산부인과학회잡지

OBJECTIVE: The phosphorylated isoforms of insulin-like growth factor-binding protein-1 (IGFBP-1) were produced by the decidua. The aim of this study was to evaluate whether the presence of phosphorylated IGFBP-1 (phIGFBP-1) in cervical secretions of pregnant women with preterm uterine contractions can predict an increased risk of preterm delivery and infectious complications. METHOD: The prospective study of 32 pregnant women who admitted under the diagnosis of preterm labor with intact membrane at gestational age of 24+0 to 36+0 weeks. Phsphorylated IGFBP-1 was qualitatively assayed using immunochromatography in cervical swab samples at the time of admission. The interval between the test and delivery, gestational age, duration of tocolysis, birth weight, CRP, ESR and the presence of neonatal infection were compared between positive and negative groups. RESULTS: There was no differnce in age, obstetric histories and gestational age and Bishop score at the time of admission between two groups. Eight pregnacies out of 13 positive group and two pregnacies out of 19 negative group resulted in preterm birth. The sensitivity and specificity of the phIGFBP-1 test to predict preterm birth were 80.0% and 77.3%, respectively. The mean getational age and interval between the test and delivery were 38.36 weeks and 45.0 days and 35.78 weeks and 35.46 days in negative and positive group respectively. The birth weight of the babies was significantly higher in negative group. The duration of tocolysis was longer in positive group with marginal statistical significance. The CRP, ESR and WBC count were not different. One postpartum sepsis, one neonatal death and one necrotizing enterocolitis were complicated in positive group. CONCLUSION: The presence of phIGFBP-1 is an usful marker to predict preterm birth in case of regular uterine contraction with intact fetal membranes.

Clinical Analysis of Midtrimester Amniocentesis / 대한주산의학회잡지

No abstract available.

A case of velamentous insertion of umbilical cord in a discordant twins conceived by in vitro fertilization / 대한산부인과학회잡지

No abstract available.

A case of cyclopia / 대한산부인과학회잡지

No abstract available.