Myometrial relaxation of mice via expression of two pore domain acid sensitive K⁺ (TASK-2) channels

Myometrial relaxation of mouse via expression of two-pore domain acid sensitive (TASK) channels was studied. In our previous report, we suggested that two-pore domain acid-sensing K⁺ channels (TASK-2) might be one of the candidates for the regulation of uterine circular smooth muscles in mice. In this study, we tried to show the mechanisms of relaxation via TASK-2 channels in marine myometrium. Isometric contraction measurements and patch clamp technique were used to verify TASK conductance in murine myometrium. Western blot and immunehistochemical study under confocal microscopy were used to investigate molecular identity of TASK channel. In this study, we showed that TEA and 4-AP insensitive non-inactivating outward K⁺ current (NIOK) may be responsible for the quiescence of murine pregnant longitudinal myometrium. The characteristics of NIOK coincided with two-pore domain acid-sensing K⁺ channels (TASK-2). NIOK in the presence of K⁺ channel blockers was inhibited further by TASK inhibitors such as quinidine, bupivacaine, lidocaine, and extracellular acidosis. Furthermore, oxytocin and estrogen inhibited NIOK in pregnant myometrium. When compared to non-pregnant myometrium, pregnant myometrium showed stronger inhibition of NIOK by quinidine and increased immunohistochemical expression of TASK-2. Finally, TASK-2 inhibitors induced strong myometrial contraction even in the presence of L-methionine, a known inhibitor of stretch-activated channels in the longitudinal myometrium of mouse. Activation of TASK-2 channels seems to play an essential role for relaxing uterus during pregnancy and it might be one of the alternatives for preventing preterm delivery.

Mechanism of Relaxation Via TASK-2 Channels in Uterine Circular Muscle of Mouse

Plasma pH can be altered during pregnancy and at labor. Membrane excitability of smooth muscle including uterine muscle is suppressed by the activation of K+ channels. Because contractility of uterine muscle is regulated by extracellular pH and humoral factors, K+ conductance could be connected to factors regulating uterine contractility during pregnancy. Here, we showed that TASK-2 inhibitors such as quinidine, lidocaine, and extracellular acidosis produced contraction in uterine circular muscle of mouse. Furthermore, contractility was significantly increased in pregnant uterine circular muscle than that of non-pregnant muscle. These patterns were not changed even in the presence of tetraetylammonium (TEA) and 4-aminopyridine (4-AP). Finally, TASK-2 inhibitors induced strong myometrial contraction even in the presence of L-methionine, a known inhibitor of stretchactivated channels in myometrium. When compared to non-pregnant myometrium, pregnant myometrium showed increased immunohistochemical expression of TASK-2. Therefore, TASK-2, seems to play a key role during regulation of myometrial contractility in the pregnancy and provides new insight into preventing preterm delivery.

Application of Mini-abdominoplasty after Conservative Excision of Extensive Cesarean Scar Endometriosis

Endometriosis is defined as the presence of functioning endometrial tissue outside the uterine cavity, and the standard treatment is extensive surgical excision. Cesarean scar endometriosis is a type of cutaneous endometriosis arising on or near a Cesarean section scar. A 44-year-old woman presented with a 9x6 cm sized dark-brown, stony-hard, irregular, lower abdominal mass of four years duration. The patient had a history of two Cesarean deliveries, 14 and 16 years ago. Suspecting endometriosis, we excised the tumor conservatively rather than extensively to prevent incisional hernia considering the benign nature of the tumor and the low possibility of recurrence because the patient's age was near menopause, along with simultaneous bilateral salpingo-oophorectomy that was performed in this case. On reconstruction, mini-abdominoplasty was adopted to avoid possible wound complications and cosmetic deformities. The patient was satisfied with the cosmetic results, and neither recurrence nor functional problems occurred during the 1-year follow-up period. Plastic surgeons should keep in mind the possibility of cutaneous endometriosis in an abdominal mass of a female of reproductive age with a previous history of pelvic or intra-abdominal surgery. An optimal result from oncological, functional, and cosmetic standpoints can be achieved with conservative excision followed by mini-abdominoplasty of extensive Cesarean scar endometriosis.

The safety of cesarean delivery through transplacental incision in anterior placenta previa / 대한산부인과학회지

OBJECTIVE: This study was to evaluate the safety of cesarean delivery through transplacental incision in anterior placenta previa and its effect on mother and neonate. METHODS: We examined 74 cases of placenta previa retrospectively who underwent cesarean section from May 2006 to December 2009, in Chungbuk National University Hospital. They were divided into two groups according to the placental incision. Transplacental incision was made in all cases of anterior placenta previa. We compared postoperative maternal hemoglobin change, neonatal hemoglobin and hematocrit, intra and/or postoperative transfusion volume, neonatal intensive care unit (NICU) admission days between the two groups. RESULTS: There were no differences in maternal characteristics, hemoglobin changes, transfusion volume between the two groups. Nor the neonatal hemoglobin and hematocrit level, Apgar score and admission days were different. There was no neonatal acidosis below pH 7.20. CONCLUSION: The cesarean delivery through transplacental incision in anterior placenta previa seems to be safe because it did not increase maternal and fetal blood loss nor NICU admission days.

Ovarian follicular and peritoneal fluid prostaglandin E2 and F2a levels according to the clinical symptoms in the women with endometriosis / 대한산부인과학회지

OBJECTIVE: The purpose of the present study was to determine whether a relationship exists between the clinical symptoms (dysmenorrhea and infertility) and prostaglandin (PG) concentrations in follicular and peritoneal fluid in the women with endometriosis during the late follicular phase of the menstrual cycle. METHODS: Thirty patients with pelvic endometriosis diagnosed by pelvic surgery were enrolled. Eight patients were suffering from severe dysmenorrhea and 11 had history of primary or secondary infertility among them. Endometriosis patients were grouped by the presence of each symptom and compared with 33 control patients without endometriosis. Peritoneal fluid was collected in the beginning of peritoneal opening and dominant follicular fluid was aspirated by syringe needle at the time of operation. Then PGE2 and PGF2a concentration were measured at each tube. RESULTS: Follicular fluid PGF2a levels were increased in 30 endometriosis patients (P=0.003), and the levels were significantly higher in 11 patients with infertility compared with the control (P=0.001). Peritoneal fluid PGF2a levels were significantly higher in 8 patients with severe dysmenorrhea compared with the others or the control (P=0.028). Follicular or peritoneal fluid PGE2 levels were not different between any group and the control. There was no significant correlation between size of endometrioma and each PG levels. CONCLUSION: Severe dysmenorrhea in endometriosis patients would be related with the high level of peritoneal fluid PGF2a concentration, and infertility in endometriosis would be related with the high level of follicular fluid PGF2a concentration.

A Preliminary Comparison of Efficacy of Intravaginal Misoprostol with Intravenous Sulprostone for Termination of Second-Trimester Pregnancy / 대한산부인과학회지

OBJECTIVE: The purpose of this study was to compare the efficacy of intravaginal misoprostol and that of intravenous sulprostone for termination of second-trimester pregnancy. METHODS: Fouty-six patients were randomly assigned to misoprostol and sulprostone group, and the misoprostol group was further divided into two groups according to gestational age. In the misoprostol group, the patients at or before 20 weeks of gestation received 400 microgram of intravaginal misoprostol every 4 hours until labor pain was established, 200 microgram every 6 hours after 20 weeks of gestation. In the sulprostone group, intravenous sulprostone was infused at the speed of 100 microgram/hr regardless of gestational age. RESULTS: At or before 20 weeks of gestation, the mean time from induction to completion of termination was shorter, and the success rate within 24 hours was higher in the misoprostol group than in the sulprostone group (9.0 vs. 20.2 hours; 86% vs 50%). After 20 weeks, the mean induction time was longer at misoprostol group than sulprostol group but, there was no significant difference in success rate within 24 hours (14.7 vs. 7.1 hours; 83% vs. 86%). There was no significant difference in the prevalence of complication between two groups. CONCLUSION: Misoprostol is superior to sulprostone for termination of pregnancy at or before 20 weeks of gestation, but both have almost equal effectiveness after 20 weeks of gestation. Considering less cost and complication, the efficacy of misoprostol should be further investigated for termination of second-trimester pregnancy.

A Case of Large Cell Neuroendocrine Carcinoma accompanied with Adenocarcinoma of the Uterine Cervix / 대한산부인과학회지

Large cell neuroendocrine carcinoma of the uterine cervix is a rare and highly aggressive cervical neoplasm. Metastases and recurrences of the tumor are common. Cervical large cell neuroendocrine carcinomas are distinctive cervical carcinomas that are frequently misdiagnosed and have unfavorable prognosis. So prudential care must be considered for proper diagnosis and multimodal treatment may be required for better survival. We experienced one case of large cell neuroendocrine carcinoma accompanied with adenocarcinoma of the uterine cervix in 52 year old woman. The uterine cervix covered and infiltrated with adenocarcinoma cells and attached polypoid mass (3.2 x 2.1 cm) composed of large cell neuroendocrine carcinoma cells. The diagnosis was confirmed by immuno-staining using cytokeratin (+), synaptophysin (+), chromogranin (+), neuron-specific enolase (+), CD 56 (+), and vimentin (-). So we report the case with brief review of the literature.

Expression of Aquaporin-4 in Placenta of Preeclampsia / 대한산부인과학회지

OBJECTIVE: This study was to determine whether aquaporin-4, which plays role as a transcellular water channel, is expressed in human placenta, and to compare the degree of its expression between preeclamptic women and normal pregnant women. METHODS: Placentas were obtained from severely preeclamptic women and normal pregnant women who were delivered neonates by cesarean section before the onset of labor in the Chungbuk National University Hospital. Immunohistochemistry with aquaporin-4 antibody was performed using paraffin-embedded tissue section. Signal of aquaporin-4 expression was observed with light microscope. RESULTS: Immunohistochemistry demonstrated expression of aquaporin-4 in the placentas of both preeclamptic women and normal pregnant women. The degree of expression was not different in both group. CONCLUSION: Aquaporin-4 was expressed in the human placenta, but may not be related to the pathogenesis of preeclampsia.

Macrophage Migration Inhibitory Factor (MIF) Concentration in the Serum of Patients with Ovarian Cysts for Differential Diagnosis of Endometrioma / 대한불임학회지

OBJECTIVE: To evaluate the usefulness of serum concentrations of macrophage migration inhibitory factor (MIF) of patients with ovarian cysts for differential diagnosis of endometrioama. METHOD: From Jan. 2003 to Dec. 2004, preoperative serum MIF levels were assessed in 28 women with endometrioma, 32 with benign epithelial tumor, 23 with functional and simple cysts, 22 with benign mature cystic teratoma, and 25 women without ovarian tumor as control. MIF levels were determined using an ELISA (Quantikine Human MIF immunoassay, R&D Systems, Inc., USA). RESULTS: Mean MIF levels were higher in all groups with benign tumors than control (all p<0.01), but there was no significant difference between benign tumor groups (p=0.95). There was no significant correlation between MIF levels and tumor volume, body mass index (BMI) (p=0.635, 0.674 respectively) Serum MIF level had significant correlation with count of WBC and neutrophils (p=0.008, 0.024 respectively), but had no correlation with count of lymhocytes and monocytes (p=0.688, 0.294 respectively). CONCLUSIONS: This study showed a marked increase in MIF concentrations in the peripheral blood of patients with endometrioma, but there was no significant difference with other benign tumors. Serum MIF level had significant correlation with count of WBC and neutrophils. These suggest serum MIF level has no usefulness for differential diagnosis of endometrioma from other benign ovarian cysts.

Cauda Equina Syndrome by Disc Prolapse after Caesarian Section Delivery / 대한주산의학회잡지

Cauda equina syndrome develops as rapidly progressive neurologic deficit of lower extremities and urogenital system often resulting in serious outcome such as complete irreversible paraparesis, therefore prompt diagnosis and decompression is mandatory. However, if it occurs after childbirth, it may be overlooked being regarded as symptoms related to pregnancy and delivery. We experienced a cauda equina syndrome by prolased disc in a 32-year-old woman just after Caesarian section who was managed with prompt decompressive surgery and achieved favorable result. Because of the importance of early detect and prompt decompression for cauda equina syndrome and possible occurrence at perinatal period, we report this case reviewing the literature especially concerning about changes of spine and disc during pregnancy and after delivery.

Expression of Aquaporin-8 in Placenta of Preeclampsia / 대한산부인과학회잡지

OBJECTIVE: This study was to determine whether aquaporin-8, which plays a role as a transcellular water channel, is expressed in human placenta, and to compare the degree of its expression between preeclamptic women and normal pregnant women. METHODS: Placentas were obtained from severely preeclamptic women and normal pregnant women who were delivered babies by cesarean section before the onset of labor in the Chungbuk National University Hospital. In situ hybridization with aquaporin-8 cRNA probe was performed using paraffin-embedded tissue section. Signal of aquaporin-8 expression was observed with light microscope. RESULTS: In situ hybridization demonstrated strong expression of aquaporin-8 mRNA in the placentas of both preeclamptic women and normal pregnant women. The degree of expression was the same in both group. CONCLUSION: Aquaporin-8 in human placenta may not be related to the pathogenesis of preeclampsia.

Vesico-Amniotic Shunting in Fetal Posterior Urethral Valve Syndrome / 대한산부인과학회잡지

Fetal posterior urethral valve syndrome results in potentially lethal complications including renal dysplasia, pulmonary hypoplasia. Antenatal fetal vesicocentesis and amniotic fluid infusion may be useful to improve neonatal pulmonary function, however rapid recurrence of urinary retention and oligohydramnios usually required repetitive invasive procedures. We successfully treated a posterior urethral valve syndrome with vesico-amniotic shunt. Under ultrasonographic guidence, we inserted a Double-Basket Catheter into fetal urinary bladder through lower abdominal wall at second trimester. Shunt remained in place until the fetus was delivered at 35th gestational week. The vesico-amniotic shunt can improve fetal outcome and avoid repeated vesicocentesis before delivery.

Angiotensinogen, Thermolabile Methylenetetrahydrofolate Reductase and Factor V Gene Variants among Korean Women with Preeclampsia, as Risk Factors / 대한산부인과학회잡지

OBJECTIVE: To know the genotypic distributions of Angiotensinogen, Thermolabile Methylenetetrahydrofolate Reductase (MTHFR) and Factor V Gene Variants, suggested as risk factors of preeclampsia, among Korean Women. METHODS: 113 preeclampsia patients and 70 normotensive pregnancy controls were evaluated. DNA was extracted from peripheral leukocytes, then PCR and restriction by appropriate enzymes were done to identify the single nucleotide polymorphism. The genotypic distributions of preeclampsia and the control group were compared. RESULTS: Nineteen of 113 women with preeclampsia (17%) and 14 of 72 with nulliparous preeclampsia (19%) were heterozygous for the angiotensinogen T704C mutation, and 94 of 113 women with preeclampsia (83%) and 58 of 72 women with nulliparous preeclampsia (81%) were homozygous. While 7/70 (10%) were heterozygous, and 59/70 (84%) were homozygous for the T704C mutation among the control subjects. The frequency of the MTHFR T677 allele was 36% in the preeclamptic group and 38% in the control group, and TT homozygosity was found in 26 preeclamptic women (23%) and in 13 controls (19%). No women were homozygous or heterozygous for the factor V Leiden mutation. CONCLUSION: Angiotensinogen T704C mutation is associated with preeclampsia in the Korean population. There was no association between the thermolabile variant of MTHFR and risk of preeclampsia in our study population. We observed no factor V Leiden mutation. We also suggested that a person with angiotensinogen T704C mutation plus MTHFR C677T variant does not have more of an increased risk for preeclampsia than with angiotensinogen T704C mutation only.

Live Birth After Expectant Management of Second Trimester Placental Abruption / 대한산부인과학회잡지

Prognosis of placental abruption depends on gestational age and the status of the mother and the fetus, and perinatal mortality was almost entirely attributable to prematurity. A midtrimester women with placental abruption was successfully treated by expectant management including fetal surveillance, serial ultrasonography and maternal hematologic examination, and delivered a healthy baby 11 weeks later. We suggest that expectant management may be considered as a good treatment option until fetal lung maturation is documented in preterm pregnancy with placental abruption if there is no maternal or fetal compromise.

Peritoneo-Amniotic Shunting in Isolated Fetal Ascites of Unknown Origin / 대한산부인과학회잡지

Although sporadic cases of transient fetal ascites have been described, pulmonary hypoplasia or hydrops fetalis may occur as potentially lethal complications of isolated fetal ascites. Antenatal fetal paracentesis may be useful in improving neonatal pulmonary function, however rapid accumulation of fluid after paracentesis usually required repetitive invasive procedures. We successfully treated an isolated fetal ascites with peritoneo- amniotic shunt. Under the ultrasonographic guidence, we inserted a Double-Basket Catheter into the left lower quadrant of fetal abdominal wall at the end of second trimester. Shunt remained in place until the fetus was delivered at term. The peritoneo-amniotic shunt can improve fetal outcome and avoid repeated paracentesis before delivery.

Preliminary Report on Efficacy of Speculoscopy for Increasing the Sensitivity of Cervical Cancer Screening Test / 대한산부인과학회잡지

OBJECTIVE: Since the accuracy of Pap smear for cervical neoplasm has been questioned, a number of adjunctive tests have been developed. The purpose of this study was to evaluate the accuracy of speculoscopy, a magnified chemiluminescent examination, as compared with that of the Pap smear in the screening of cervical neoplasm. METHODS: A total of 41 women were included in the study. We conducted Pap smear, speculoscopy, and punch biopsy to all subjects. Targeted biopsies were obtained from any suspicious lesions that were found with positive speculoscopy. Women with negative speculoscopy underwent random biopsies. The data were analysed using McNemar's test. RESULTS: Thirty-one out of 41 biopsy specimen were found to have cervical lesion that were worse than CIN I, including 8 cases of invasive cancer. The sensitivity and specificity of Pap smear were 74.2% and 70.0%, respectively. Those of speculoscopy were 93.5% and 60.0%, respectively. When these two tests were combined, the sensitivity was raised to 96.8%, but the specificity declined to 50.0%. Among 9 cases of ASCUS on Pap smear, 6 cases were found to have cervical pathology worse than CIN II, and these were positive on speculoscopy. CONCLUSION: Speculoscopy combined with a Pap smear can increase the detection of cervical lesions compared with the Pap smear alone. In the cases of ASCUS on Pap smear, speculoscopy may be more useful to detect significant pathology.

Factor V Gene Polymorphism with Preeclamptic Women in Korea / 대한산부인과학회잡지

OBJECTIVE: This study was to evaluate the association of the G1691A mutation of factor V gene with preeclamptic patients in Korea. METHODS: Factor V genotype were determined in 113 preeclamptic patients and 100 normotensive pregnant women. A 267 base-pair DNA fragment of the factor V gene that includes nucleotide 1691 was amplified by PCR. PCR product was digested with MnlI restriction enzyme and the fragments were analysed by electrophoresis using 2% agarose gel. RESULTS: The difference of genetic and allelic frequencies between two groups could not be mentioned because all women were G1691G homozygotes. There was no individuals with mutant allele among preeclamptic patients and control women. CONCLUSION: There was no evidence of association between preeclampsia and factor V gene polymor- phism in Korean population.

A comparison of Clinical Efficacy of Intravaginal Misoprostol with Intravenous Sulprostone for Termination of Second-Trimester Pregnancy / 대한산부인과학회잡지

OBJECTIVE: Our purpose was to compare the clinical efficacy of intravaginal misoprostol and that of intravenous sulprostone for termination of second-trimester pregnancy. METHODS: The patients were assigned to misoprostol and sulprostone group, and the misoprostol group was further divided into two groups according to gestational age. In the misoprostol group, the patients at or before 20 weeks of gestation received 400 microgram of intravaginal misoprostol every 4 hours until labor pain was established, 200 microgram every 6 hours after 20 weeks of gestation. In the sulprostone group, intravenous sulprostone was infused at the speed of 100 microgram/hr after cervical ripening with 3 mg of intravaginal dinoprostone. RESULTS: At or before 20 weeks of gestation, the median time from induction to completion of termination was longer, but the success rate within 24 hours was less in the misoprostol group than in the sulprostone group (18.75 vs. 7.15 hours, p=0.015; 50% vs 92%, p=0.014, respectively). After 20 weeks, there was no significant difference in median induction time or success rate within 24 hours (5.54 vs. 8.0 hours, p>0.05; 100% vs. 100%, p>0.05, respectively). There was no significant difference in the prevalence of complication or change of hemoglobin after termination between two groups. CONCLUSION: Sulprostone may be more effective for termination of pregnancy at or before 20 weeks of gestation and misoprostol may be as effective as sulprostone after 20 weeks of gestation. But considering less cost and complication, the efficacy of misoprostol should be further investigated for termination of second- trimester pregnancy.

Conservative Treatment of Viable Cervical Pregnancy with Intra-amniotic Methotrexate / 대한산부인과학회잡지

OBJECTIVE: The purpose of this study was to determine the effectiveness of intra-amniotic methotrexate instillation for the treatment of viable cervical pregnancy. MATERIALS AND METHODS: Four patients were enrolled in this study after confirmation of cervical pregnancy by ultrasonography. Viable cervical pregnancy was determined by ultrasonographic findings with the entire chorionic sac containing a live fetus below the internal os, empty uterine cavity, and significantly dilated or barrel shaped cervical canal. Under the transvaginal ultrasonographic guidence, 50 mg of methotrexate was injected directly into the amniotic sac after complete aspiration of amniotic fluid. Serial serum beta-human chorionic gonadotropin (beta-hCG) was evaluated weekly until normalized. RESULTS: All the patients were successfully treated with conservative method and one patient received hysterectomy due to arterio-venous malformation diagnosed during follow up. Initial serum beta-hCG concentration was 22,484-93,803 mIU/ml and decreased by log scale after treatment. CONCLUSION: Intra-amniotic methotrexate instillation without concomitant feticide injection or feticidal procedure can be used for the initial treatment in viable cervical pregnancy. Initial titer or falling rate pattern of serum beta-hCG did not seem to be related with the prognosis.

Thermolabile Methylenetetrahydrofolate Reductase Gene Variants in Korean Women with Severe Preeclampsia / 대한산부인과학회잡지

OBJECTIVE: This study was performed to evaluate C to T substitution at nucleotide 677 of meth-ylenetetrahydrofolate reductase gene in Korean women, which is genetically homogeneous, with preeclamptic or normotensive pregnancies. METHODS: Methylenetetrahydrofolate reductase genotypes were determined in 63 Korean women with severe preeclamptic pregnancies and 60 controls with normotensive pregnancies, using polymerase chain reaction and restriction enzyme analysis. RESULTS: The methylentetrahydrofolate reductase genotype and allele frequencies in preeclamptic and control women did not differ significantly. The frequency of the T677 allele was 38.1% in the preeclamptic group and 41.7% in the control group, and TT homozygosity was found in 12 preeclamptic women (19.0%) and 10 controls (16.7%). CONCLUSION: It seems like that there is no evidence of association of preeclampsia with meth-ylenetetrahydrofolate reductase gene polymorphism, at least in the Korean population.