Fetal Hydrops Associated With 47,XXX: A Case Report and Literature Review.

This report aims to investigate the association between 47,XXX and fetal hydrops by examining a clinical case and performing a comprehensive review of the relevant literature. A 34-year-old Japanese woman, gravida 2, para 1, was diagnosed with fetal hydrops at 27 weeks' gestation. Prenatal testing revealed a 47,XXX karyotype. Interventions included thoracocentesis and a thoracoamniotic shunt. A cesarean delivery was performed at 34 weeks and the female neonate initially had respiratory challenges. After 69 days in the neonatal intensive care unit, the infant was discharged in stable condition, and the 47,XXX karyotype was confirmed. This case may add evidence suggesting an association between 47,XXX and fetal hydrops. Chromosomal abnormalities are causes of fetal hydrops, but its association with 47,XXX remains unclear. Providing comprehensive information on this condition to couples is crucial, and considering the inclusion of fetal hydrops in the list of associated conditions might be advisable.

Uterine contraction may not be an independent risk factor for spontaneous preterm birth before 35 weeks in women with cervical shortening.

OBJECTIVE: To compare the risk of spontaneous preterm birth (SPTB) before 35 weeks in symptomatic and asymptomatic women with cervical shortening at 16-34 weeks under mid-trimester universal screening of cervical length (CL). METHOD: Multicenter retrospective cohort study involving six secondary/tertiary perinatal centers was planned in 2016. Primary outcomes were SPTB before 35 weeks. In all, 407 women were analyzed using multivariable logistic regression analysis for predicting SPTB before 35 weeks while adjusting for presence/absence of uterine contraction, gestational weeks, vaginal bleeding, and CL classification (1-9, 10-14, 15-19, and 20-24 mm) at admission, the execution of cervical cerclage, and the presence/absence of past history of preterm delivery. RESULTS: SPTB before 35 weeks of pregnancy occurred in 14.5%. Presence of uterine contraction was not an independent risk factor for SPTB before 35 weeks (adjusted odds ratio [aOR] 1.22, 95% confidence interval [CI] 0.67-2.20). CL of 1-9 mm, CL of 10-14 mm, and vaginal bleeding at admission were independent risk factors for SPTB before 35 weeks (aOR 5.35, 95% CI 2.11-13.6; aOR 2.79, 95% CI 1.12-6.98; and aOR 2.37, 95% CI 1.12-5.10, respectively). CONCLUSION: In women with a cervical shortening at 16-34 weeks, presence of uterine contractions at admission may not be an independent risk factor for the occurrence of SPTB before 35 weeks.

Role of Collagen Gel Droplet-Embedded Culture-Drug Sensitivity Testing (CD-DST) for Assessing the Sensitivity of Gastric Cancer to Chemotherapy Drugs Combined with Other Cancer Therapeutic Drugs.

BACKGROUND: Chemosensitivity tests have long been a widely discussed research topic. Our group performed collagen gel droplet-embedded culture-drug sensitivity testing (CD-DST) of patients with advanced gastric cancer during the period from December 2012 to December 2017. To verify how CD-DST should be used, we invested correlations of sensitivities to cisplatin (CDDP), docetaxel (DOC), paclitaxel (PTX), and CPT11 with clinical outcome. METHODS: Patients with advanced gastric cancer underwent gastrectomy with lymph node dissection at Nippon Medical School Tama Nagayama Hospital, and surgical samples were retrospectively examined by CD-DST to assess chemosensitivity. The patients later received adjuvant chemotherapy as standard adjuvant therapy or chemotherapy. The CD-DST test was not performed for S-1 because it is commonly used in chemotherapy for gastric cancer. Although oxaliplatin has also recently become a key drug for advanced gastric cancer, it had not been adopted for gastric cancer in 2012, so CD-DST testing was not performed. The χ2 test was used for all statistical analyses. A p-value of <0.05 was assumed to indicate statistical significance. Three-year survival rates were estimated using the Kaplan-Meier method, and the log-rank test was used to compare the obtained curves. RESULTS: Of the tumors from gastric cancer patients, 67.0% (77/115) could be cultured. The rate of sensitivity was 41.1% (30/73) for CDDP, 82.6% (57/69) for DOC, 82.8% (58/70) for PTX, and 49.2% (33/67) for CPT11. CDDP sensitivity and outcome were not correlated in patients who received CDDP. Sensitivities to CDDP, DOC, PTX, and CPT11 were not correlated with any patient characteristic. Patients with poorly differentiated adenocarcinoma tended to be sensitive to CDDP (P=0.051). CONCLUSIONS: No difference between CDDP sensitivity or outcome was observed in patients receiving CDDP. The CD-DST showed a high sensitivity to DOC and PTX in the present patients.

Effects of prophylactic vaginal progesterone administration on mild cervical shortening (TROPICAL study): a multicenter, double-blind, randomized trial.

Vaginal progesterone reduces the preterm birth frequency among high-risk women with a cervical length ≤25 mm at midtrimester. However, the strategy may promote no substantial reduction in overall preterm birth rates, because such high-risk women are only approximately 2% of all pregnant women, which restrict the number of participants. Our purpose was to determine whether prophylactic vaginal progesterone administration can preserve cervical length and reduce preterm birth rates among women with mild cervical shortening.This multicenter, parallel-arm, double-blind, randomized, placebo-controlled trial involved vaginal progesterone administration (200 mg daily from 16 to 33 weeks of gestation) among asymptomatic women with a singleton pregnancy and a sonographic cervical length of 25 to <30 mm between 16 and 23 weeks of gestation. The primary and secondary endpoints were cervical shortening rates at 34 weeks of gestation and preterm birth rates, respectively. The trial was registered at the University Hospital Medical Information Network (UMIN000013518) in Japan.Between April 2014 and March 2018, 119 women were randomly assigned to the progesterone group (n = 59) and the placebo group (n = 60). No significant differences in the frequency of women with a cervical length ≥20 mm at 34 weeks of gestation were observed between both groups. All preterm births occurred after 34 weeks of gestation, except for one patient in the placebo group. The progesterone group had a lower rate of preterm birth before 37 weeks than the placebo group (3.4% vs. 15.0%, respectively; p < .05).Despite having no effect on preserving cervical length, prophylactic vaginal progesterone administration reduced preterm birth frequency among women with mild cervical shortening. Our results are suggesting that women with mild cervical shortening are at risk for late preterm birth and the need for expanding progesterone treatment indications to include not only high-risk but also low-risk populations.

Cervical Dilatation Curves of Spontaneous Deliveries in Pregnant Japanese Females.

Background: Although cervical dilatation curves are crucial for appropriate management of labor progression, abnormal labor progression and obstetric interventions were included in previous and widely-used cervical dilatation curves. We aimed to describe the cervical dilatation curves of normal labor progression in pregnant Japanese females without abnormal labor progression and obstetric interventions. Methods: We completed retrospective obstetric record reviews on 3172 pregnant Japanese females (parity = 0, n = 1047; parity = 1, n = 1083; parity ≥ 2, n = 1042), aged 20 to 39 years old at delivery, with pregravid body mass indices of less than 30. All patients underwent spontaneous deliveries with term, singleton, cephalic and live newborns of appropriate-for-gestational age birthweight, without adverse neonatal outcomes. We characterized labor progression patterns by examining the relationship between elapsed times from the full dilatation and cervical dilatation stages, and labor durations by examining the distribution of time intervals from one cervical dilatation stage, to the next, and ultimately to the full dilatation. Results: Fastest cervical changes occurred at 6 cm (primiparas) and 5 cm (multiparas) of dilatation. The 95%tile of labor progression took over 3 hours to progress from 6 cm to 7 cm (primiparas), and over 2 hours to progress from 5 cm to 6 cm (multiparas). The 5%tile of traverse time to the full dilatation, during the active phase, was less than 1 hour (primiparas) and 0.5 hours (multiparas). At the end of the active phase, no deceleration phase was observed. Conclusions: Active labor may not start until 5 cm of dilatation. At the beginning of the active phase, cervical dilatation was slower than previously described. These results may reduce opportunities for obstetric interventions during labor progression.

High-throughput separation of cells by dielectrophoresis enhanced with 3D gradient AC electric field.

We propose a novel, high-performance dielectrophoretic (DEP) cell-separation flow chamber with a parallel-plate channel geometry. The flow chamber, consisting of a planar electrode on the top and an interdigitated-pair electrode array at the bottom, was developed to facilitate the separation of cells by creating a nonuniform AC electric field throughout the volume of the flow chamber. The operation and performance of the device were evaluated using live and dead human epithermal breast (MCF10A) cells. The separation dynamics of the cell suspension in the flow chamber was also investigated by numerically simulating the trajectories of individual cells. A theoretical model to describe the dynamic cell behavior under the action of DEP, including dipole-dipole interparticle, viscous, and gravitational forces, was developed. The results demonstrated that the live cells traveling through the flow chamber congregated into sites where the electric field gradient was minimal, in the middle of the flow stream slightly above the centerlines of the grounded electrodes at the bottom. Meanwhile, the dead cells were trapped on the edges of the high-voltage electrodes at the bottom. Cells were thus successfully separated with a remarkably high separation ratio (∼98%) at the appropriately tuned field frequency and applied voltage. The numerically predicted behavior and spatial distribution of the cells during separation also showed good agreement with those observed experimentally.

Impact of the Great East Japan Earthquake and Fukushima Nuclear Power Plant Accident on Assisted Reproductive Technology in Fukushima Prefecture: The Fukushima Health Management Survey.

BACKGROUND: The aim of the study was to evaluate the incidences and obstetric outcomes of women who conceived using assisted reproductive technology (ART) procedures in Fukushima Prefecture before and after the Great East Japan Earthquake and Fukushima nuclear power plant accident. METHODS: Information was collected and analyzed from 12,070 women who conceived with or without ART in Fukushima Prefecture during the 9 months before and after the disaster. RESULTS: During the 9 months before and after the disaster, 138 (2.0%) and 102 (1.9%) women conceived with in vitro fertilization-embryo transfer (IVF-ET), respectively. The proportion of women who conceived with IVF-ET decreased during the 2 months immediately after the disaster, but returned to pre-disaster levels 3 months after the disaster. In the case of women who conceived without IVF-ET, the incidences of preterm birth and low birth weight increased after the disaster. In contrast, women who conceived with IVF-ET did not differ significantly in obstetric outcomes before and after the disaster but had a higher incidence of cesarean section and low birth weight compared to those conceived without IVF-ET, regardless of the study period. CONCLUSION: The influence of the disaster on woman who conceived using ART procedures was minimal.

Standard curves of placental weight and fetal/placental weight ratio in Japanese population: difference according to the delivery mode, fetal sex, or maternal parity.

OBJECTIVES: Placental weight (PW) and fetal/placental weight ratio (F/P) have been considered to be useful parameters for understanding the pathophysiology of fetal growth. However, there have been no standard data on PW and F/P in Asian populations. This study was conducted to establish nomograms of PW and F/P in the Japanese population and to clarify characteristics of PW and F/P in this population. STUDY DESIGN: Included in the study were 79,590 Japanese cases: 58,871 vaginal and 20,719 cesarean deliveries at obstetrical facilities (2001-2002) and registered to the Japan Society of Obstetrics and Gynecology Database. Multiple pregnancies, stillbirths, and fetal anomalies were excluded. Nomograms of PW and F/P were created by spline methods in groups categorized by fetal sex (male or female) and maternal parity (primipara or multipara). RESULTS: Standard curves of PW and F/P were established, which indicated that PW and F/P were lower in cesarean deliveries than vaginal deliveries, especially during preterm period. PW differed depending on fetal sex and maternal parity. F/P differed according to fetal sex. CONCLUSION: We for the first time established standard curves of PW and F/P in the Japanese population with statistically sufficient data, which showed that PW and F/P were lower in cesarean deliveries. PW and F/P were also affected by fetal sex. These data might be useful to understand the pathophysiology between the fetus and placenta in utero.

Fetal/Placental weight ratio in term Japanese pregnancy: its difference among gender, parity, and infant growth.

PURPOSE: The "inappropriately heavy placenta" has been considered to be associated with various pregnancy disorders; however, data is scarce what factors affect it. To determine whether the following three affect it; (1) infant gender and mother's parity, (2) growth restriction, and (3) preeclampsia. METHODS: We employed fetal/placental weight ratio (F/P). Subjects consisted of 53,650 infants and their placentas from women who vaginally delivered singleton live term infants. First, we examined whether F/P differs among the infant's gender or mother's parity. We classified the population into 4 categories according to gender and parity: male, nulliparous (n=7,431), male, multiparous (n=7,859), female, nulliparous (n=7,559), female, multiparous (n=7,800), and, compared F/P among the four groups. Next, we determined whether F/P differs in "small" or "large" for gestational age (SGA or LGA) infants, compared with appropriate for gestational age infants. Last, we determined whether preeclampsia (representative disorder of SGA) affects F/P. RESULTS: (1) F/P significantly differed according to infant gender and parity: female and nulliparity had significantly smaller F/P. F/P was significantly smaller in (2) SGA infants, and (3) infants from preeclamptic mothers. CONCLUSION: We for the first time showed that in Japanese term vaginally-delivered singleton population, the following three had significantly smaller F/P than controls thus had "inappropriately heavy placenta": (1) female gender and nulliparity, (2) SGA infants, and (3) infants from preeclamptic mothers. We recommend that these factors should be taken into account in evaluating placental weight. These data may also be useful for further clarifying the fetal-placental pathophysiology in these conditions.

The effect of single embryo transfer on perinatal outcomes in Japan.

OBJECTIVE: In 2007 and 2008, the Japan Society for Reproductive Medicine and the Japan Society of Obstetrics and Gynecology issued a recommendation for single embryo transfer (SET). Thereafter, SET was implemented in 73% of in vitro fertilization (IVF) cases in Japan. The purpose of this study was to evaluate the effects of compliance with the SET recommendation on perinatal outcomes. METHODS: An electronic audit of the perinatal database of the Japanese Society of Obstetrics and Gynecology was conducted from 2001 through 2010. The database comprised data of 610,726 women. Totally, 20,923 women conceived through IVF. To compare perinatal outcomes, these women were categorized into two study groups depending on whether they conceived before (2004-2005, n=3,865) or after (2009-2010, n=6,842) the SET recommendation statement was issued. RESULTS: The proportion of women who conceived through IVF increased from 1.3% in 2001 to 4.8% in 2010. Compliance with the SET recommendation led to a decrease in the incidence of twin pregnancies (33.9% versus 13%, p<0.01), incidence of preterm delivery (odds ratio [OR]: 0.54, 95% confidence interval [CI]: 0.50-0.59), low birth weight (OR: 0.42, 95% CI: 0.39-0.45), and neonatal intensive care unit admission (OR 0.70, 95% CI 0.65-0.76), but an increase in the incidence of monochorionic twins (1.6% versus 2.5%, p<0.01). CONCLUSION: Compliance with the SET recommendation improved perinatal outcomes by reducing the incidence of twin pregnancies.

Type and location of placenta previa affect preterm delivery risk related to antepartum hemorrhage.

PURPOSE: To evaluate whether type and location of placenta previa affect risk of antepartum hemorrhage-related preterm delivery. METHODS: We retrospectively studied 162 women with singleton pregnancies presenting placenta previa. Through observation using transvaginal ultrasound the women were categorized into complete or incomplete placenta previa, and then assigned to anterior and posterior groups. Complete placenta previa was defined as a placenta that completely covered the internal cervical os, with the placental margin >2 cm from the os. Incomplete placenta previa comprised marginal placenta previa whose margin adjacent to the internal os and partial placenta previa which covered the os but the margin situated within 2 cm of the os. Maternal characteristics and perinatal outcomes in complete and incomplete placenta previa were compared, and the differences between the anterior and the posterior groups were evaluated. RESULTS: Antepartum hemorrhage was more prevalent in women with complete placenta previa than in those with incomplete placenta previa (59.1% versus 17.6%), resulting in the higher incidence of preterm delivery in women with complete than in those with incomplete placenta previa [45.1% versus 8.8%; odds ratio (OR) 8.51; 95% confidence interval (CI) 3.59-20.18; p < 0.001]. In complete placenta previa, incidence of antepartum hemorrhage did not significantly differ between the anterior and the posterior groups. However, gestational age at bleeding onset was lower in the anterior group than in the posterior group, and the incidence of preterm delivery was higher in the anterior group than in the posterior group (76.2% versus 32.0%; OR 6.8; 95% CI 2.12-21.84; p = 0.002). In incomplete placenta previa, gestational age at delivery did not significantly differ between the anterior and posterior groups. CONCLUSION: Obstetricians should be aware of the increased risk of preterm delivery related to antepartum hemorrhage in women with complete placenta previa, particularly when the placenta is located on the anterior wall.

Adverse obstetric and perinatal outcomes of singleton pregnancies may be related to maternal factors associated with infertility rather than the type of assisted reproductive technology procedure used.

OBJECTIVE: To compare obstetric and perinatal outcomes of singleton pregnancies conceived with different types of assisted reproductive technology (ART) procedures with those of naturally conceived pregnancies. DESIGN: Retrospective cohort study. SETTING: The perinatal database of the Japanese Society of Obstetrics and Gynecology. PATIENT(S): A total of 242,715 women with singleton pregnancies were examined as a base cohort. Three study groups were created according to the type of ART procedure used, namely ovulation stimulation medications (n = 4,111), IUI (n = 2,351), and IVF-ET (n = 4,570). Controls adjusted for multiple maternal characteristics were selected randomly for each study group. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Obstetric and perinatal outcomes. RESULT(S): Patients who conceived through the ART procedures were associated with an increased incidence of placenta previa, preterm delivery, and low birth weight infant and a decreased incidence of spontaneous cephalic delivery, regardless of the type of ART procedure. CONCLUSION(S): Among singleton pregnancies, patients conceived with ART procedures were at increased risk for several adverse obstetric and perinatal outcomes, regardless of the type of ART procedure used. These results suggest that maternal factors associated with infertility may contribute to the adverse outcomes rather than the ART procedures themselves.

Fetal heart rate classification proposed by the perinatology committee of the Japan Society of Obstetrics and Gynecology: reproducibility and clinical usefulness.

AIM: Intrapartum management guidelines based on fetal heart rate classification comprising a 5-tier system (Levels 1-5) was proposed by the Perinatology Committee of the Japan Society of Obstetrics and Gynecology (JSOG). This study aimed to assess the reproducibility and clinical usefulness of this classification. METHODS: For assessing intraobserver and interobserver reproducibility in the interpretation of fetal heart rate tracing, 2 obstetricians reviewed 247 fetal heart rate tracings using the JSOG classification (Level 1, normal; Level 2, benign variant; Level 3, mild variant; Level 4, moderate variant; and Level 5, severe variant) and a subjective 3-tier classification (normal, equivocal, and ominous). In a separate series, we investigated whether the JSOG classification is related to early neonatal outcome and the delivery mode in 96 deliveries. RESULTS: Weighted kappa coefficients of intraobserver and interobserver reproducibility in the interpretation of fetal heart rate tracings based on the JSOG classification were 0.73 to 0.77 and 0.70, respectively. In the subjective classification, these values were 0.69 to 0.72 and 0.59. There was a progressive increase in the rate of instrumental or cesarean deliveries across the 5 levels of the JSOG classification (P<0.001). Although, level 5 of the JSOG classification had a lower Apgar score and umbilical artery pH than did the other 4 levels (p<0.05), there were no significant differences among the other levels in regard to early neonatal outcome. CONCLUSIONS: This study demonstrated that both intraobserver reproducibility and interobserver reproducibility of the JSOG classification for interpreting FHR tracings were clinically acceptable. The results also suggest that the intervention according to the JSOG classification is useful for avoiding worsening early neonatal outcomes.

Effect of urinary trypsin inhibitor on preterm labor with high granulocyte elastase concentration in cervical secretions.

AIMS: To explore whether intravaginal treatment with urinary trypsin inhibitor (UTI) prevents preterm delivery in patients in preterm labor with increased levels of granulocyte elastase in cervical secretions. METHODS: The subjects were patients in preterm labor with increased levels of granulocyte elastase in cervical secretions from 16 to 33 weeks gestation. Maternal and neonatal outcomes were compared between patients receiving UTI treatment (UTI group; n=33) and those not receiving UTI treatment (control group; n=40). RESULTS: In patients receiving UTI, the mean gestational age at delivery was greater than that in the control group (37.8 vs. 35.6 weeks, p=0.003), and the rates of premature delivery before 34 and 37 weeks gestation were lower (3% vs. 20%, p=0.028; and 18% vs. 47%, p=0.008, respectively). The percentage of neonates weighing more than 2,500 g was significantly higher in the UTI group, with no neonates weighing less than 1,500 g. The neonatal hospitalization rate was lower in the UTI group (9% vs. 42%, p=0.001). CONCLUSION: In patients in preterm labor with a high elastase concentration in cervical secretions, treatment with UTI reduced the risk of preterm delivery and improved neonatal outcomes.

Factors influencing the accuracy of digital examination for determining fetal head position during the first stage of labor.

OBJECTIVE: The objective of this study was to explore factors influencing the accuracy of transvaginal digital examination for determining fetal head position during the first stage of labor. MATERIALS AND METHODS: Fetal head position was assessed in 87 women in the first stage of labor at term with normal singleton cephalic presentation. Transvaginal digital examinations were performed by attending midwives and were followed immediately by transabdominal ultrasound assessments performed by a single sonographer. Accuracy was defined as agreement of the results of each examination. Multivariate logistic regression analysis was performed to determine the independent factors influencing accuracy. RESULTS: In only 40.3% of patients (n = 35) were transvaginal digital examinations consistent with ultrasound assessments. Multivariate logistic regression analysis showed that the accuracy of digital examinations was significantly associated with cervical dilatation more than 7 cm (odds ratio, 3.01; 95% confidence interval [CI], 1.03-9.4), birth weight less than 2,500 g (odds ratio, 8.68; 95% CI, 1.08-86.28), and the anterior occiput position group (odds ratio, 4.73; 95% CI, 1.76-13.49). CONCLUSIONS: The present study demonstrates that transvaginal digital examination is less accurate than ultrasonography for determining fetal head position during the first stage of labor. The results suggest that ultrasound assessments should be routinely performed in patients with a cervical dilatation less than 7 cm, an estimated fetal body weight more than 2,500 g, the occiput posterior position, or the occiput transverse position.

Inductive potential of recombinant human granulocyte colony-stimulating factor to mature neutrophils from x-irradiated human peripheral blood hematopoietic progenitor cells.

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) has been used for treatment of neutropenia. Filgrastim, Nartograstim, and Lenograstim are clinically available in Japan. However, the differences in potential benefit for radiation-induced disorder between these types of rhG-CSFs remain unknown. Therefore, the effects of three different types of rhG-CSFs on granulocyte progenitor cells and expansion of neutrophils from nonirradiated or 2 Gy X-irradiated human CD34+ hematopoietic progenitor cells were examined. For analysis of granulocyte colony-forming units (CFU-G) and a surviving fraction of CFU-G, nonirradiated or X-irradiated CD34+ cells were cultured in methylcellulose containing rhG-CSF. These cells were cultured in serum-free medium supplemented with rhG-CSF, and the expansion and characteristics of neutrophils were analyzed. All three types of rhG-CSFs increased the number of CFU-G in a dose-dependent manner; however, Lenograstim is superior to others because of CFU-G-derived colony formation at relatively low doses. The surviving fraction of CFU-G was independent of the types of rhG-CSFs. Expansion of neutrophils by rhG-CSF was largely attenuated by X-irradiation, though no significant difference in neutrophil number was observed between the three types of rhG-CSFs under both nonirradiation and X-irradiation conditions. In terms of functional characteristics of neutrophils, Lenograstim-induced neutrophils produced high levels of reactive oxygen species compared to Filgrastim, when rhG-CSF was applied to nonirradiated CD34(+) cells. In conclusion, different types of rhG-CSFs lead to different effects when rhG-CSF is applied to nonirradiated CD34+ cells, though Filgrastim, Nartograstim, and Lenograstim show equal effects on X-irradiated CD34+ cells.

Disruption of HDAC4/N-CoR complex by histone deacetylase inhibitors leads to inhibition of IL-2 gene expression.

Previous studies have shown that HDAC inhibitors selectively inhibit IL-2 gene expression, but the mechanism of this inhibition remains to be elucidated. It was recently reported that HDAC4, a component of the nuclear hormone receptor corepressor (N-CoR) complex, associates with the IL-2 promoter via the transcription factor myocyte enhancer factor 2 (MEF2). We therefore focused on the role of HDAC4/N-CoR complex in the transcriptional regulation of IL-2. Four approaches were used to characterize this role and to investigate the relation between the regulatory function of HDAC4/N-CoR complex and HDAC4-enzymatic activity: (i) HDAC4 silencing by RNA interference, (ii) overexpression of N-CoR repression domain 3 (RD3), (iii) overexpression of HDAC4 point mutants, and (iv) treatment with HDAC inhibitors. Here, we report that HDAC4 plays an essential role in IL-2 promoter activation, and that the formation of the HDAC4/N-CoR complex, which is closely related to HDAC4-enzymatic activity, might be involved in HDAC inhibitor-mediated inhibition of IL-2 gene expression. These observations indicate that the selective inhibition of HDAC4 or the interaction of HDAC4 with N-CoR is likely a potential target for the development of novel immunosuppressants.

Incidence and risk factors for severe perineal laceration after vaginal delivery in Japanese patients.

OBJECTIVE: The aim of this study was to assess the frequency of severe perineal lacerations defined as either third- or fourth-degree lacerations during normal spontaneous vaginal delivery and to evaluate potential risk factors in Japanese patients. MATERIALS AND METHODS: An electronic audit of the perinatal database at the Tama-Nagayama Hospital of Nippon Medical School and Yamaguchi Hospital from 1997 through 2004 was completed. Singleton vaginal vertex deliveries were analyzed for potential risk factors using univariate and multivariate logistic regression analysis. RESULTS: From the database, 7,946 deliveries were identified, with 135 deliveries resulting in severe lacerations (1.7%). In the multivariate logistic regression analysis, severe lacerations were associated significantly with primiparous (odds ratio, 4.36; 95% CI, 2.17-9.57), oxytocin use (odds ratio, 2.19; 95% CI, 1.27-3.73), midline episiotomy (odds ratio, 4.68; 95% CI, 2.09-11.55), forceps-assisted delivery (odds ratio, 7.11; 95% CI, 1.95-20.59), vacuum-assisted delivery (odds ratio, 5.93; 95% CI, 3.38-10.36), and shorter attendant experience (odds ratio, 2.88; 95% CI, 1.12-9.81). CONCLUSIONS: The present study demonstrated that operator factors, such as midline episiotomy, oxytocin use, assisted delivery and attendant experience, are independent risk for severe perineal lacerations after vaginal delivery in Japanese patients. The results suggest that midline episiotomy and assisted vaginal delivery, especially forceps-assisted delivery should be avoided in patients who are being delivered of a first child whenever possible.