Kimisato Asano

Oral valganciclovir treatment for congenital cytomegalovirus infection

Congenital cytomegalovirus (CMV) infection is the most common intrauterine infection. Approximately 10–15% of congenitally infected neonatal infants exhibit clinical evidence of congenital infection at birth. This group is more likely to experience sequelae, including microcephalus, sensor neural hearing loss, cognitive, motor and visual deficits and seizures. Previous studies have shown that approximately half of the children with symptomatic congenital CMV infection develop hearing loss, and the majority of these children experience continued postnatal deterioration of their hearing. Ganciclovir is an antiviral agent that acts against herpes viruses and has been used successfully to treat CMV infection. In addition, it has been reported that ganciclovir therapy, begun in the neonatal period in symptomatic infants with a CMV infection involving the central nervous system, prevents hearing deterioration. However, the efficacy of ganciclovir for hearing deterioration in patients beyond the neonatal period is unknown. In this report we present the case of a five-month-old girl who was treated with oral valganciclovir for progressive hearing loss resulting from congenital CMV infection.

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.

Nitric oxide donor-induced inhibition of pregnant rat uterine spontaneous contractile activity and release of nitric oxide from uterus measured by microdialysis.

Our aim was to study whether nitric oxide (NO) donor-induced inhibition of pregnant rat myometrium contractility correlates with the release of NO. Uterine rings from mid-pregnant and late pregnant Sprague-Dawley rats were used for isometric tension recording. Concentration-response relationships to sodium nitroprusside (SNP), nitroglycerine (NTG) and diethylamine (DEA)/NO were assessed. The time course of NO release after addition to the organ chambers of the 3 NO-donors was assessed by the detection of NO products NOx (NO3+NO2) using the microdialysis probe by a HPLC-NO detector system. DEA/NO induced greater inhibition of the spontaneous contractile activity of uterine rings from mid-pregnant rats than SNP or NTG. In uterine rings from late pregnant rats, however, the maximal inhibition of the contractility by all 3 NO-donors were significantly less. The NOx levels measured in the uterine ring walls from either mid-pregnant or late pregnant rats significantly increased after DEA/NO as compared to the basal levels or the levels after NTG or SNP. The decrease of NO-donor-induced inhibition of rat myometrium contractility, with unchanged formation of NOx, at term, suggests that the changes in NO signaling are responsible for gestational age-dependent attenuation of the inhibitory effect.

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

ABSTRACT 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.

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

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.

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.

Effects of sex steroids on expression of adenylyl cyclase messenger RNA in rat uterus

The aim of our study was to investigate the effects of estradiol (E2) and/or progesterone (P4) bilateral ovariectomized rats on gene expressions of adenylyl cyclases (AC2, AC4, AC6, AC9). Non-pregnant (NP) Wister rats (between post-natal 10 and 12 weeks) and normal pregnant rats (between postnatal 10 and 14 weeks) were used. NP rats were divided into five groups: 1) control NP rats, 2) ovariectomy rats (OVX), 3) OVX injected with E2 (6 μg) for 4 days (E2), 4) OVX injected with P4 (5 mg) for 4 days (P4), 5) ovariectomy rats injected with E2 (6 μg) and P4 (5 mg) for 4 days (E2/P4). The ovariectomized rats were sacrificed by anesthesia of diethyl ether after 24 h from the last injection. The pregnant group was sacrificed in the same way on 14 (P14), 17 (P17) and 21 (P21) of pregnancy, because the days between P14 and P17 were the second trimester of pregnancy and P21 was the third trimester. Total RNA were prepared from the uteri of each subject, and expression of ACs was analyzed by reverse transcription-polymerase chain reaction (RT-PCR). Expression of mRNAs for AC2, AC4, AC6 and AC9 were maximally increased on P17 and then decreased on P21. In OVX rats, expression of mRNAs for AC2, AC4, and AC9 were decreased as compared to NP. AC2 mRNA was significantly increased by E2 treatment. AC4 and AC9 mRNA was significantly increased by injection of E2 or P4. AC6 mRNA level was not affected by E2 and/or P4. In conclusion, AC2, AC4 and AC9 gene expression is affected by estrogen and/or P4. On the contrary, AC6 gene expression was not changed by OVX or hormone treatment. Since, all ACs mRNA examined here are increased during pregnancy, AC6 may be affected by other factor(s) other than estrogen and P4.

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.