Unique Learning System for Uterine Artery Embolization for Symptomatic Myoma and Adenomyosis for Obstetrician-Gynecologists in Cooperation with Interventional Radiologists: Evaluation of UAE From the Point of View of Gynecologists Who Perform UAE.

STUDY OBJECTIVE: To evaluate a unique learning system for uterine artery embolization (UAE) and examine its feasibility and clinical outcomes for the treatment of symptomatic uterine leiomyomas and adenomyosis when performed by obstetrician-gynecologists in cooperation with interventional radiologists (IVRs). DESIGN: Retrospective study (Canadian Task Force classification II-2). SETTING: University hospital. PATIENTS: One hundred seventy-three patients who underwent UAE for symptomatic leiomyomas and adenomyosis. INTERVENTIONS: We examined the medical records of patients who underwent UAE for symptomatic uterine leiomyomas and adenomyosis at our department between 2003 and 2012 using our learning system for UAE for obstetrician-gynecologists in cooperation with IVRs. The charts of all patients were reviewed, and data on etiologic factors, past medical history of leiomyomas and adenomyosis, symptoms, details of UAE, and clinical outcomes after UAE were extracted. MEASUREMENTS AND MAIN RESULTS: A total of 173 patients who underwent 177 UAEs were identified, including 4 patients who underwent embolization twice because of primary treatment failure or symptom recurrence. During the study period, 2 gynecologists successfully acquired endovascular skills. The technical success rate was 97.7% (174 of 177). The duration of fluoroscopy in procedures performed by obstetrician-gynecologists who acquired endovascular skills was not significantly different from that in procedures performed by IVRs at our institution; however, this duration was significantly longer in procedures performed by obstetrician-gynecologists who did not have sufficient experience with our learning protocol for UAE because of inadequate live observation of UAEs performed by skilled IVRs. Complications that necessitated discontinuation of the procedure occurred in 2.3% of cases (4 of 177). The clinical outcomes were similar to those reported in previous studies. Adverse events after UAE included myeloid passages in 7.0% (11 of 158), infections in 2.5% (4 of 158), vaginal discharge in 2.5% of patients with leiomyomas (4 of 158), and vaginal discharge in 7.1% of patients with adenomyosis (1 of 14). All the adverse events were adequately treated by the obstetrician-gynecologists themselves. The timing of hysterectomy due to complications or recurrence of symptoms after UAE varied widely. CONCLUSION: UAE performed by obstetrician-gynecologists in cooperation with radiologists can be achieved safely and successfully with acceptable clinical outcomes. Live observation of the procedure performed by skilled IVRs is essential to improving the skills and reducing the fluoroscopic time of obstetrician-gynecologists.

Congenital cytomegalovirus in Japan: More than 2 year follow up of infected newborns.

BACKGROUND: The aim of this study was to evaluate the outcome of congenital cytomegalovirus (CMV) infection identified on urine-filter screening assay at >2 years' follow up, and to observe the clinical outcomes after anti-CMV treatment. METHODS: Sixty of 72 congenital CMV patients were enrolled and clinically observed for >2 years. Forty-three were asymptomatic at birth; seven were symptomatic at birth but untreated with anti-CMV drugs; and 10 were symptomatic and treated with anti-CMV drugs. RESULTS: Of the 43 asymptomatic patients, three developed hearing loss or language disability for which association with congenital CMV has been repeatedly reported, and two had neurological sequelae of which the etiology was unclear, indicating that the rate of CMV-associated late-onset sequelae was 7-12%. All seven symptomatic infants without treatment developed sequelae, while three of the 10 treated patients were free from any sequelae. CONCLUSIONS: The rate of late-onset sequelae observed in Japan is similar to that reported in the USA and Europe. The treatment of symptomatic patients with antiviral agents results in favorable clinical outcomes. Thus, newborn urine-filter paper screening of congenital CMV infection is warranted.

A novel real-time PCR method for determination and quantification of each cytomegalovirus glycoprotein H subtype in clinical samples.

To investigate reinfection in patients with congenital cytomegalovirus (CMV) infection, we established a CMV subtype-specific real-time quantitative PCR method targeting the CMV gH epitope region that can be used for evaluating pathogenic CMV strains in cases of mixed CMV infection.

Effect of lipopolysaccharide on the production of prostaglandin E2 and inhibition of uterine contractions by nitric oxide in pregnant inducible nitric oxide synthase knockout mice.

AIM: The aim of the present study was to evaluate the effect of lipopolysaccharide (LPS) on the production of prostaglandin E2 (PGE2) and inhibition by nitric oxide (NO) of spontaneous contractions of uterine rings from pregnant inducible isoform of nitric oxide synthase knockout (iNOS KO) mice. MATERIAL AND METHODS: iNOS KO and wild-type mice were sacrificed 6 h after intraperitoneal (i.p.) administration of LPS on day 14 of gestation. Uterine rings were equilibrated in Krebs-Henseleit solution for isometric tension recording. In part of the uterine rings, placental tissues were left attached. The bathing solution was analyzed for PGE2 by radioimmunoassay. Changes in spontaneous contractions in response to cumulative concentrations of L-arginine, diethylamine/nitric oxide (DEA/NO), and 8-bromo-cyclic guanosine monophosphate (8-br-cGMP) were determined. RESULTS: Treatment with LPS increased PGE2 production by uterine rings from wild-type and iNOS-KO mice. DEA/NO and 8-br-cGMP inhibited spontaneous contractions in uterine rings in the absence or presence of placenta, in both LPS-treated and LPS-untreated animals. LPS treatment attenuated maximal inhibition induced by the agents, both in the absence and presence of placental tissues in iNOS KO and wild-type mice. CONCLUSION: LPS induces PG production in mice myometrium that is not dependent on the integrity of iNOS, while LPS could induce pathophysiological iNOS obstruct uterine quiescence by physiological iNOS. Infection affects uterine contractile activity through PG production, as well as through placental and genetic factors. NO may be a double-edged sword in pregnant mice myometrium.

Cytomegalovirus (CMV) glycoprotein H-based serological analysis in Japanese healthy pregnant women, and in neonates with congenital CMV infection and their mothers.

BACKGROUND: Congenital cytomegalovirus (CMV) infection is caused by maternal primary infection as well as CMV reinfection or reactivation during pregnancy, although differences in the clinical impact between these modes of infection remain to be clarified. OBJECTIVES: To investigate the latest prevalence and risk of multiple CMV infection in healthy pregnant women, as well as the types of maternal CMV infection associated with congenital CMV infection. STUDY DESIGN: Seroprevalence against CMV and IgG subclasses were determined in 344 serum samples from healthy pregnant women in Japan. CMV genotype and serotype were also determined in 18 pairs of mothers and neonates with congenital CMV infection identified in our CMV screening program. RESULTS: Thirty-two percent of the pregnant women were seronegative, while 66% of CMV seropositive women had IgG3 antibodies against one epitope on glycoprotein H (gH) as the major subclass, and 52% had IgG1 antibodies against one epitope on glycoprotein B (gB). Only a single genotype determined by CMV gH neutralizing epitope was found in the urine from the 18 neonates with congenital CMV infection, even though one case possessed antibodies against multiple CMV strains. In that case, the antibodies against the strain not detected in the urine from the infant disappeared within one month after birth, whereas the antibodies against the infecting CMV strain continued to be detected at 12 months after birth. CONCLUSIONS: Two (11%) of 18 cases of congenital CMV infection occurred via maternal CMV reinfection. Maternal humoral immunity did not prevent congenital CMV infection with another gH subtype.

Screening for congenital cytomegalovirus infection using newborn urine samples collected on filter paper: feasibility and outcomes from a multicentre study.

Background As congenital cytomegalovirus (CMV) infection causes significant clinical consequences not only at birth but also later as neurological sequelae, it is critical to establish a strategy for screening congenitally infected newborns. Previous studies have identified an insufficient sensitivity in screening methods based on the use of dried blood spots (DBSs). Objectives To evaluate the feasibility of the authors' recently developed method for large-scale screening for congenital CMV infection and to identify risk factors for congenital infection. Methods More than 21 000 newborns were enrolled at 25 sites in six geographically separate areas of Japan. Urine was collected onto filter cards placed in the diapers, which were then analysed by quantitative PCR using the filter disc directly as a template. Clinical and physical findings of the newborns were extracted from their medical records. CMV strains from the cases and their siblings were genetically compared. Viral loads in DBSs obtained from some of the cases were compared with those in the urine filters. Results Congenital CMV infection was identified in 0.31% (95% CI 0.24% to 0.39%) of the newborns, and 30% of the cases (20/66) had typical clinical manifestations and/or showed abnormalities in brain images at birth. Although the positive predictive value of our screening was 94%, the lack of any comparison with a gold standard assay prevented calculation of the negative predictive value. Almost two-thirds of the cases had siblings, a significantly higher frequency than for uninfected newborns. Most of the cases (21/25) excreted CMV strains identical to those of their siblings. CMV DNA was undetectable in three out of 12 retrievable DBS specimens. Conclusions Implementation of an effective large-scale screening programme for congenital CMV infection is feasible. Siblings are the major risk factor for congenital CMV infection, which emphasises the need for education of mothers-to-be as well as vaccine development.

Diagnosis and management of primary aldosteronism in pregnancy: case report and review of the literature.

Primary aldosteronism rarely complicates pregnancy. We present a woman with primary aldosteronism in pregnancy associated with severe preeclampsia. A 33-year-old Japanese woman with hypertension was referred to our hospital at 25 weeks of gestation. Her blood pressure was 180/100 mmHg, and laboratory tests identified a low serum potassium level and moderate proteinuria on urinalysis. The fetus was diagnosed with growth restriction. Plasma renin activity (PRA) value was 2.2 ng/mL/h and plasma aldosterone concentration (PAC) was elevated (260 pg/mL). The patient was treated medically. At 27 weeks of gestation, we noted persistent late fetal heart rate decelerations associated with uterine contractions. Therefore, elective caesarean section was performed and she was delivered of a 698-g female. After delivery, PRA declined and PAC remained elevated. Abdominal computerized tomography scan and I131-iodochoresterol scan revealed a tumor in the left adrenal gland. Laparoscopic adrenalectomy was performed and confirmed the clinical diagnosis.

Expression of iNOS mRNA and inhibitory effect of NO on uterine contractile activity in rats are determined by local rather than systemic factors of pregnancy.

Our purpose was to investigate whether the local or systemic factors of pregnancy are associated with inducible nitric oxide synthase (iNOS) mRNA expression and to determine the inhibitory effects of pharmacological agents that increase cGMP levels in rat myometrium. iNOS mRNA expression was determined in uterine tissues from nonpregnant rats and on day 17 of gestation in the pregnant and non-pregnant uterine horns by RT-PCR. In addition, uterine rings from the pregnant and non-pregnant uterine horns were placed in Krebs-Henseleit solution for isometric recordings of spontaneous contractions. Concentration-inhibition relationships to diethylamine/nitric oxide complex, 8-bromo-cGMP, and the selective phosphodiesterase V inhibitor were obtained. Compared to nonpregnant rats, expression of iNOS mRNA in myometrium increased during pregnancy, which was maximal on day 17, followed by a decrease on day 21 of gestation. Expression of iNOS mRNA at day 17 of gestation was greater in pregnant uterine horns than in nonpregnant ones. Maximal inhibition of phosphodiesterase V and increasing cGMP induced similar inhibition of spontaneous contractions in nonpregnant and pregnant uterine horns, while NO induced less inhibition in the former. The results suggest that the local pregnancy factor is needed for signal transduction from NO to soluble guanylate cyclase at a time when maximal expression of iNOS mRNA is evident.