Relationship between prolonged gestation and nifedipine pharmacokinetics in long-term tocolysis.

In this study, we examined the pharmacokinetics of nifedipine and investigated the maternal and foetal background factors that prolong pregnancy in pregnant women undergoing long-term tocolysis. This prospective observational study included 38 pregnant women hospitalised for threatened preterm labour and treated with nifedipine extended-release tablets in combination with an intravenous ritodrine infusion. Maternal plasma nifedipine concentrations were determined using high-performance liquid chromatography. All patients were administered 20 or 40 mg/dose of nifedipine every 6 h at the time of blood sampling. The plasma trough concentration (Ctrough ) was 22.6 ± 17.3 ng/mL, the maximum plasma concentration (Cmax ) was 30.9 ± 15.3 ng/mL and the time to maximum concentration (Tmax ) was 1.70 ± 1.10 h, as determined using noncompartmental analysis (NCA). The area under the curve for drug concentration (AUCtau ) was 152.3 ± 91.8 mg/L・h, and oral clearance (CL/F) was 0.17 ± 0.08 L/h. Using logistic regression analyses, we identified the factors that predicted term delivery from 37 weeks to <42 weeks of gestation. Gestational age at admission and the AUCtau of nifedipine can predict term delivery. The AUCtau of nifedipine is a valuable regulatory predictor of term delivery in pregnant women undergoing long-term tocolysis.

Novel compound heterozygous mutations in the PLEC gene in a neonate with epidermolysis bullosa simplex with pyloric atresia.

Epidermolysis bullosa (EB) is a heterogeneous group of inherited disorders characterized by the blistering of the skin and mucous membranes. Although the molecular basis of EB has been significantly elucidated, the precise phenotypes of the lethal types of EB have not been completely characterized. Herein, we report a severe case of EB with pyloric atresia (PA). The patient was a Japanese boy who not only had skin lesions but also various complications such as PA, dysphagia, hypotonia, infectious keratitis with corneal ulcer, obstructive uropathy and protein-losing enteropathy. Genetic analysis led to the identification of two novel compound heterozygous mutations in the last exon of the plectin (PLEC) gene. Based on this finding, EB simplex with PA was diagnosed. Immunostaining with anti-plectin antibodies revealed truncated plectin proteins lacking the C-terminus in the patient's skin. We also conducted a prenatal diagnosis in subsequent pregnancy. Our report further highlights the crucial role of plectin in many organs and provides valuable information regarding the phenotypes resulting from mutations in the PLEC gene.

A case of total hysterectomy due to massive maternal bleeding immediately after fetoscopic laser surgery for twin-twin transfusion syndrome.

Twin-twin transfusion syndrome (TTTS) complicates approximately 10% of monochorionic twin pregnancies and is associated with almost 90% mortality if left untreated. Fetoscopic laser photocoagulation (FLP) is the first-line therapy for TTTS, and an overall twin survival rate of 75% and at least one survival rate of 90% have been established. We report a case of TTTS complicated with bleeding from the uterine wall by inserting the procedure after FLP. The patient consequently underwent emergency caesarean section. The bleeding was uncontrollable due to atonic bleeding and emergency hysterectomy was performed. To detect the possibility of amniotic fluid embolism (AFE), biochemical blood samples demonstrated that there was no inflow of fetal ingredients in blood vessels of uterine tissue. There was no evidence of damage to any specific vessels by histopathological staining. These findings indicated that the cause of massive bleeding was unlikely to have been AFE. It was concluded that atonic bleeding was likely caused by uncontrollable hemorrhage from an injury lesion where an endoscope had been inserted.

Interleukin-8 Levels in the Stratum Corneum as a Biomarker for Monitoring Therapeutic Effect in Atopic Dermatitis Patients.

INTRODUCTION: The stratum corneum contains several growth factors and cytokines that are synthesized in keratinocytes. We previously reported that the amount of interleukin-8 in the stratum corneum (scIL-8) is related to the severity of local skin inflammation in atopic dermatitis (AD). However, it is unknown whether scIL-8 levels reflect pharmacologic responses to a therapeutic intervention in AD patients. Therefore, in this study, we aimed to investigate whether the improvement of dermatitis in AD is correlated with scIL-8 levels before and after topical corticosteroid treatment. METHODS: Stratum corneum samples were collected from 22 AD patients using the noninvasive tape-stripping method before treatment, 2 weeks after topical treatment, and 4-6 weeks after treatment. RESULTS: scIL-8 levels on the forearm reduced significantly from 790 ± 348 pg/mg before treatment to 163 ± 68 pg/mg 2 weeks after treatment and 100 ± 37 pg/mg 4-6 weeks after corticosteroid treatment. scIL-8 levels on the abdomen also reduced significantly from 902 ± 391 to 142 ± 38 pg/mg at the end of study. The reduction in scIL-8 levels was associated with the improvement in local skin severity in AD. We also found that scIL-8 levels, along with blood biomarker levels (serum thymus and activation-regulated chemokine, lactate dehydrogenase, and %eosinophil), decreased significantly after the treatment. CONCLUSION: The scIL-8 concentration decreases with improvements in skin symptoms in AD patients after topical corticosteroid treatment; thus, it may be a suitable biomarker for monitoring therapeutic effects in AD patients.

Distribution of PAPP-A and total hCG between 11 and 13 weeks of gestation in Japanese pregnant women.

Objectives: To establish the reference values for PAPP-A and total hCG between 11 and 13 weeks of gestation for the use of risk assessment of fetal aneuploidy in Japanese pregnant women.Methods: A multicenter prospective study was conducted. The subjects included only Japanese pregnant women with viable singleton who requested the first trimester combined (nuchal translucency and maternal serum marker) screening for fetal aneuploidy. Reference values of PAPP-A and total hCG in Japanese population were made and compared with them in Caucasian.Results: Overall 1,751 Japanese pregnant women were analyzed. Median vales of maternal serum concentration in Japanese pregnant women from 11 + 0-13 + 6 weeks' gestation were ranged from 3.01 to 9.51 mIU/mL for PAPP-A and from 70.2 to 58.3 IU/mL for total-hCG, respectively. Regression curve of median maternal serum PAPP-A and total-hCG concentration against gestational days are significantly higher in Japanese comparing with Caucasian. At most distant values, Japanese serum concentration indicated 1.45 MoM for total-hCG and 1.70 MoM for PAPP-A based on Caucasian regression curves.Conclusion: A modification of the equations by specific reference values is necessary for Japanese pregnant women at the risk assessment of chromosomal abnormalities using the first trimester maternal serum marker.

Prevalence of right ventricular outflow tract abnormalities among recipients in twin-twin transfusion syndrome after fetoscopic laser surgery in 90 consecutive cases.

PURPOSE: Right ventricular outflow tract obstruction (RVOTO) is a severe complication in recipients in twin-twin transfusion syndrome (TTTS). This study investigated the prevalence of RVOTO in TTTS after laser surgery and examined the risk factors for RVOTO. METHODS: This retrospective study evaluated 90 patients who had undergone laser surgery and been followed for 6 months after birth. The diagnosis of RVOTO was made based on postnatal echocardiography findings. Ultrasound and clinical records, including maternal and neonatal data, were retrieved from our database. Risk factors for developing RVOTO were compared between recipients with and without RVOTO in a statistical analysis. RESULTS: Six surviving recipients were diagnosed with RVOTO. Three recipients had developed severe pulmonary stenosis (PS) that required percutaneous transluminal pulmonary valvuloplasty or balloon pulmonary angioplasty. A total of 6.7% of recipients (6/90) had RVOTO, consisting of PS and tricuspid regurgitation (TR), and 3.3% of recipients (3/90) required invasive treatment. The characteristic factors did not differ significantly between recipients with and without RVOTO. CONCLUSION: This study revealed that 6.7% of recipients with TTTS had PS, and 3.3% required invasive treatment for PS. However, no significant association was noted between RVOTO development in recipients and maternal clinical data and fetal ultrasound examination findings. It is difficult to predict RVOTO development in recipients using only preoperative ultrasound and clinical information.

In vitro Antifungal Activity of Japanese Folk Herb Extracts against Trichophyton rubrum.

Folk herbs are vital to the Japanese health care system, with some being used to treat fungal skin infections. We tested folk herbs used in traditional Japanese medicine for in vitro antifungal activity against Trichophyton rubrum, the most common pathogen in patients with superficial dermatitis. Acetone, ethanol, methanol, water, and acetic acid extracts from 15 species of Japanese folk herbs (Bi-wa, Aka-me-gashiwa, Ta-mushi-ba, Yomogi, Shi-so, Ku-ko, So-ba, Yama-momo, Kuro-mo-ji, Ichi-ji-ku, Kaki-no-ki, Kuwa-no-ki, Kusa-gi, Chimaki-zasa, and I-bukijya-kou-sou) were evaluated for fungal growth inhibition, as measured by absorbance. Crude acetic acid extracts of Aka-me-gashiwa, Ta-mushi-ba, Yomogi, Ku-ko, Kaki-no-ki, and I-bukijya- kou-sou exhibited antifungal activity comparable to that of amphotericin B. Although the active compounds and underlying antifungal mechanisms are not known, the data contribute to the development of new and safe antifungal drugs, highlight new extraction methods for herbs, and support the traditional use of Japanese folk herbs against fungal infections.

Reproducibility of automated fetal heart rate measurement using a novel technique with two-dimensional tracking.

PURPOSE: To assess the accuracy of automated fetal heart rate measurement using two-dimensional tracking (AutoFHR) by comparison with the conventional free-angle M-mode (M-mode) and pulsed-waved Doppler (PWD) methods. METHODS: A multicenter prospective comparative study was conducted. AutoFHR is a novel technique for the automatic calculation of fetal heart rate using a two-dimensional speckle-tracking method. The fetal heart rate (FHR) obtained by AutoFHR was compared with that obtained by the conventional M-mode and PWD. Statistical analysis was performed on the correlation between the FHR measured by AutoFHR and that determined by M-mode and PWD. RESULTS: Data from 326 singleton pregnancies were analyzed, and all the data and the data from 178 cases were compared with M-mode and PWD, respectively. The intraobserver ICC was 0.96 (95% CI: 0.93-0.98), whereas the interobserver ICC was 0.97 (95% CI: 0.95-0.99). Systematic bias was not observed between M-mode and PWD, based on the Bland-Altman plots. Analyses of the relationships among the FHRs yielded by each method revealed that AutoFHR was strongly associated with M-mode (rs = 0.99, p < 0.001) and PWD (rs = 0.86, p < 0.001). CONCLUSION: Evaluation of FHR by AutoFHR was proved to be equivalent to evaluation by the conventional M-mode and PWD. AutoFHR can be employed with only B-mode data, making FHR measurement easier and safer.

[A Case Report of Surgery and Chemotherapy for a Patient with Rapidly Progressing Breast Cancer during Pregnancy].

A 33-year-old woman became aware of a right breast mass at her 28th week of pregnancy. From the biopsy results, we diagnosed her with right breast cancer. At her 33rd week of pregnancy, she underwent modified radical mastectomy (pT2N3aM0, Stage III C, ER-negative, PR-negative, HER2-positive), and she elected to receive adjuvant therapy after the surgery during her pregnancy. She received the first course of EC (epirubicin plus cyclophosphamide) therapy on the 13th postoperative day (35 weeks of gestation) and gave a natural, vaginal delivery at 36 weeks and 5 days of gestation. On the 4th day after birth, the patient noticed a contralateral left breast mass and was diagnosed with left breast cancer, after core needle biopsy. She received 4 courses of EC therapy and is currently undergoing PTX plus HER (paclitaxel plus trastuzumab) therapy. Regarding chemotherapy during pregnancy, we recommend that there is no need to perform artificial preterm birth, because chemotherapy has little influence on children after their second-trimester. After the second-trimester, chemotherapy can be safely performed.

Chorioamniotic Membrane Separation after Fetoscopic Laser Photocoagulation.

INTRODUCTION: This study aimed to investigate the risk factors, incidence, and influence on the perinatal outcome of chorioamniotic membrane separation (CMS) after fetoscopic laser photocoagulation (FLP). MATERIAL AND METHODS: This retrospective study included 312 women who underwent FLP for twin-to-twin transfusion syndrome (TTTS). Clinical records were used to review obstetrical examinations, complications, operative data, ultrasonographic findings, and perinatal and neonatal follow-up data in all patients. RESULTS: A total of 260 cases of TTTS were analyzed. The incidence of CMS was 12.7% (33 cases). The only independent risk factor of CMS was performing FLP before 20 weeks of gestational age (GA) (odds ratio = 3.38 [1.44-7.93], p = 0.005). Concerning perinatal outcome, CMS was only related with increased risk of premature rupture of membranes (PROM) before 32 weeks (33.3 vs. 13.9%, p = 0.005), with no differences in GA at delivery and survival rate. DISCUSSION: In our cohort, the incidence of CMS after FLP was approximately 13%, with surgery before 20 weeks being the only risk factor identified. Although in our population CMS did not worsen perinatal outcome in terms of preterm delivery or survival, the preterm PROM rate was increased and this should be considered for the patients' management.

The experience of modified sequential selective laser photocoagulation of communicating vessels technique for twin-twin transfusion syndrome.

OBJECTIVE: Fetoscopic laser photocoagulation of vascular anastomoses (FLP) is the essential choice in twin-twin transfusion syndrome (TTTS). We proposed that the modified sequential selective laser photocoagulation of communicating vessels (modified SQLPCV) to clarify the perinatal outcomes in TTTS. METHODS: The modified SQLPCV was designed with the following order: 1, artery-to-artery anastomoses; 2, venous-to-venous anastomoses; 3, artery-to-venous anastomoses from donor to recipient; and 4, artery-to-venous anastomoses from recipient to donor. The perinatal outcomes were present in TTTS patients who underwent the modified SQLPCV. RESULTS: A total of 203 women underwent modified SQLPCV. The mean pregnancy prolongation period was 83 days, and the mean gestational age at delivery was 33 weeks (range 23-40 weeks). There was a significantly lower rate of recipient fetal demise than donor fetal demise (4% vs. 13%; p < .01). The survival rate of zero and one were respectively 6% (13/203) and 19% (39/203). Two survivors were seen in 74% (151/203), and at least one survivor in 94% (190/203). Univariate and multivariate analysis showed that abnormal fetal Doppler measurements in donor were correlated with donor demise after surgery. CONCLUSIONS: The modified SQLPCV represents satisfactory outcomes for fetuses complicating with TTTS.

Usefulness of Sweat Management for Patients with Adult Atopic Dermatitis, regardless of Sweat Allergy: A Pilot Study.

Background. Sweat is an aggravating factor in atopic dermatitis (AD), regardless of age. Sweat allergy may be involved in AD aggravated by sweating. Objective. We investigated whether sweat exacerbates adult AD symptoms and examined the extent of sweat allergy's involvement. Method. We asked 34 AD patients (17 men, 17 women; mean age: 27.8 years) to record the extent to which sweat aggravated their symptoms on a 10-point numerical scale. Participant responses were compared with histamine release tests (HRT). Furthermore, 24 of the patients received instructions on methods of sweat management, and their outcomes were evaluated on a 10-point scale. Results. Sweat HRT results were class ≥ 2 in 13 patients, but HRT results were not correlated with the patients' self-assessments of symptom aggravation by sweat. One month after receiving sweat management instructions, a low mean score of 4.6 was obtained regarding whether active sweating was good, but a high mean score of 7.0 was obtained in response to whether the sweat management instructions had been helpful. Conclusion. Our investigation showed that patients' negative impressions of sweat might derive from crude personal experiences that are typically linked to sweating. Sweat management for patients with adult atopic dermatitis was extremely useful regardless of sweat allergy.

A prospective pilot study of fetoscopic laser surgery for twin-to-twin transfusion syndrome between 26 and 27 weeks of gestation.

OBJECTIVE: The aim of this study is to clarify the feasibility and efficacy of fetoscopic laser photocoagulation of placental vascular communicating vessels (FLP) on twin-twin transfusion syndrome (TTTS) after 26 weeks of gestation. MATERIALS AND METHODS: This is a prospective pilot study investigating all cases of TTTS between 26 weeks and 27 weeks during 2012 and 2013 in Japan. The primary endpoints in this study were the feasibility of FLP and rate of harmful complications for the mother's health. Also, perinatal prognosis was investigated. RESULTS: Six cases were enrolled and underwent FLP. Two of the six cases were classified preoperatively as Quintero Stage II and four cases were Stage III. FLP was completely achieved in all six cases. No severe maternal complications were noted during and immediately after the surgery. All but one case continued the pregnancies > 14 days after FLP. The median gestational age at delivery was 33.4 weeks (28.0-36.6 weeks). All 12 fetuses survived at the 28(th) day in the neonatal period. No case was diagnosed with cerebral lesion at the neonatal period. CONCLUSION: This prospective pilot study shows that FLP could be a therapeutic option for TTTS between 26 weeks and 27 weeks of gestation.

Ratio of fetal anteroposterior to transverse cerebellar diameter for detection of the cerebellar hypoplasia in the second trimester and comparison with trisomy 18.

AIM: Cerebellar hypoplasia, particularly, trisomy 18, represents a chromosomal abnormality. However, morphological assessment of the fetal cerebellum is yet to be established. The purpose of this study was to produce reference values for the fetal transverse cerebellar diameter (TCD), anteroposterior cerebellar diameter (APCD) and the ratio of APCD to TCD (APCD/TCD ratio) in normal fetuses, compared with cases of trisomy 18. METHODS: This retrospective study included 266 normal singleton pregnancies resulting in term delivery at our institution from 2012-2013. Patients had received ultrasound examinations in the second trimester. TCD and APCD measurements were performed and then APCD/TCD ratio was calculated. Consequently, three cases of trisomy 18 were compared with reference values. RESULTS: Gestational age correlated with TCD (rs = 0.766, P < 0.0001) and APCD (rs = 0.61, P < 0.0001), but not with APCD/TCD ratio (rs = 0.070, P = 0.252). The median APCD/TCD ratio was 0.52 and the standard deviation was 0.05. In cases of trisomy 18, all TCD measurements were located within normal ranges. In contrast, both the APCD and APCD/ TCD ratio displayed lower values than that of normal fetuses. CONCLUSIONS: This study showed that not only TCD but also APCD correlated with gestational age, and APCD/TCD ratio indicated a fixed value (almost 0.5) in normal fetuses. Furthermore, APCD and APCD/TCD ratio were deemed useful indicators for cerebellar hypoplasia. In particular, the APCD/TCD ratio proved more convenient, without requiring individual evaluation of TCD and APCD.

Experience of fetoscopic laser photocoagulation and cord transection for twin-reversed arterial perfusion sequence.

AIM: The purpose of this study was to evaluate the usefulness of fetoscopic laser photocoagulation of placental communicating vessels or umbilical cord for twin-reversed arterial perfusion (TRAP) sequence. MATERIAL AND METHODS: We report a retrospective case series of all cases of TRAP sequence identified from 2006 to 2014 at out institutions. Fetoscopic laser photocoagulation of placental arterioarterial and venovenous anastomoses was performed in diamniotic twins, and in cases of monoamniotic twins we performed laser photocoagulation and transection of the umbilical cord of the acardiac twin to prevent cord entanglement. Pregnancy and perinatal outcomes were estimated. RESULTS: Ten cases were included in the study. The median gestational age at procedure was 21.3 weeks (range, 16.7-27.3 weeks). All cases completed the procedure. Two cases were treated with laser photocoagulation and transection of the umbilical cord of the acardiac twin. No major immediate complications were noted. Preterm rupture of membranes occurred in four cases (40%). One case resulted in miscarriage. The other fetuses were delivered alive. Median gestational age at delivery was 35.4 weeks (range, 25.6-42.0 weeks). Median interval of treatment to delivery was 85 days (range, 43-153 days). Five out four infants were delivered preterm. The overall neonatal survival was 9/10. CONCLUSION: This case series demonstrated favorable outcome, and fetoscopic laser photocoagulation seems to be a useful treatment for TRAP sequence. In particular, transection of the umbilical cord is effective to prevent cord entanglement of monoamniotic twins.

[Full Recovery from Cardiopulmonary Arrest caused by Traumatic Asphyxia].

Traumatic asphyxia is a crush injury of the chest characterized by facial edema, cyanosis, conjunctival hemorrhage, and petechiae on the face and chest. The prognosis depends on the duration of chest compression and early cardiopulmonary resuscitation after cardiopulmonary arrest. Here we report a case of full recovery from cardiopulmonary arrest caused by traumatic asphyxia. The chest of a 56-year-old man was compressed by a machine while working. Immediately, his colleague started cardiopulmonary resuscitation, which was successful. When he was admitted to our hospital, his consciousness level was E1V2M2(Glasgow coma scale). Our treatment included therapeutic hypothermia, the duration of which was 24 hours at 34 °C. Rewarming his body to 36 °C took place over 48 hours. Thereafter, he recovered completely and was discharged on the 12th hospital day without neurologic sequela. Therapeutic hypothermia was possibly effective in this case.

New zoonotic cases of Onchocerca dewittei japonica (Nematoda: Onchocercidae) in Honshu, Japan.

BACKGROUND: Zoonotic infections with Onchocerca species are uncommon, and to date only 25 clinical cases have been reported worldwide. In Japan, five previous zoonotic infections were concentrated in Oita, Kyushu (the southern island), with one previous case in Hiroshima in the western part of Honshu (the main island). The causative agent in Japan was identified as Onchocerca dewittei japonica Uni, Bain & Takaoka, 2001 from Japanese wild boars (Sus scrofa leucomystax Temminck, 1842). Here we report two infections caused by a female and male O. dewittei japonica, respectively, among residents of Hiroshima and Shimane Prefectures in the western part of Honshu. METHODS: In both cases, nodules were surgically removed. The parasites in nodules were identified on the basis of their histopathological characteristics. Identification was confirmed by sequencing the mitochondrial cytochrome c oxidase subunit 1 (cox1) gene from worms in the tissues used in the histological preparations. RESULTS: Case 1 was a 61-year-old woman from Hiroshima Prefecture who complained of a painful subcutaneous nodule on the back of her right hand. The causative agent was identified as a female O. dewittei japonica owing to transverse ridges on the cuticle and molecular analysis. Case 2 was a 78-year-old woman from Shimane Prefecture who had a painful nodule in the left temporal region. Histopathological characteristics and cox1 sequencing of the worm indicated that the causative agent was a male O. dewittei japonica. CONCLUSIONS: For Cases 1 and 2, we diagnosed the causative agents as a female and male O. dewittei japonica, respectively. These findings indicate the spread of a zoonosis caused by O. dewittei japonica in the western part of Honshu, where wild boars have recently extended their habitats because of decreased annual snowfall, unused rice fields and a decline in the number of hunters in Japan. The O. dewittei japonica infection rate among wild boars was reported as 78% in Shimane Prefecture, in the western part of Honshu. Therefore, in the near future, zoonotic onchocercosis is likely to occur in Honshu as well as Kyushu, where wild boars, blackfly vectors and humans share the same habitat.