The TGF-ß/UCHL5/Smad2 Axis Contributes to the Pathogenesis of Placenta Accreta.

Placenta accreta is a high-risk condition causing obstetric crisis and hemorrhage; however, its pathogenesis remains unknown. We aimed to identify the factors contributing to trophoblast invasiveness and angiogenic potential, which in turn drive the pathogenesis of placenta accreta. We focused on the transforming growth factor (TGF)-ß1-Smad pathway and investigated the intrinsic relationship between the time- and dose-dependent inhibition of the ubiquitinating enzyme UCHL5 using bAP15, a deubiquitinase inhibitor, after TGF-ß1 stimulation and the invasive and angiogenic potential of two cell lines, gestational choriocarcinoma cell line JEG-3 and trophoblast cell line HTR-8/SVneo. UCHL5 inhibition negatively regulated TGF-ß1-induced Smad2 activation, decreasing extravillous trophoblast invasiveness. Smad1/5/9 and extracellular signal-regulated kinase (ERK) were simultaneously activated, and vascular endothelial growth factor was secreted into the trophoblast medium. However, extravillous trophoblast culture supernatant severely impaired the vasculogenic potential of human umbilical vein endothelial cells. These results suggest that the downstream ERK pathway and Smad1/5/9 potentially regulate the TGF-ß1-Smad pathway in extravillous trophoblasts, whereas Smad2 contributes to their invasiveness. The abnormal invasive and angiogenic capacities of extravillous cells, likely driven by the interaction between TGF-ß1-Smad and ERK pathways, underlie the pathogenesis of placenta accreta.

Continuous monitoring of fetal gross movement and maternal glucose level using newly developed methods.

BACKGROUND: There is no consensus on the relationship between maternal glucose levels and fetal movements. OBJECTIVE: This study aimed to investigate the correlation between gross fetal movements and maternal glucose levels in the hours around food intake. STUDY DESIGN: This was an observational study with 2 newly developed technologies, which were a glucose monitoring system and a fetal movement acceleration measurement recorder. A total of 15 women with singleton pregnancies were provided with the glucose monitoring system that automatically recorded their glucose levels every 15 minutes. In addition, fetal movements were recorded using the fetal movement acceleration measurement recorder, for 4 hours starting from 1 hour before lunch, once a week beginning at 28 weeks of gestation. For the four 1-hour periods, the ratios of the number of 10-second epochs with fetal movement divided by the total number of epochs (defined as the fetal movement parameter) were compared at the earlier (28-33 weeks of gestation), later (34-39 weeks of gestation), and overall (28-39 weeks of gestation) gestational weeks using analysis of variance analyses. A linear regression analysis was developed between the glucose level and the movement parameter for the earlier, later, and overall gestational weeks. All data were divided into 4 categories: (1) both the glucose level and the fetal movement parameter increased from the previous 15 minutes; (2) the glucose level increased, but the fetal movement parameter did not increase; (3) the glucose level did not increase, but the fetal movement parameter increased; and (4) both glucose level and fetal movement parameter did not increase. The numbers for each category were compared for the earlier, later, and overall gestational weeks using χ2 analyses. RESULTS: There was no significant change in the fetal movement parameter among the four 1-hour periods at the earlier (P=.509), later (P=.884), and overall (P=.816) gestational weeks. There was a positive correlation between the glucose level and the movement parameter at 28 to 33 weeks of gestation (P=.001), but not at 33 to 39 (P=.129) and 28 to 39 (P=.115) weeks of gestation. Compared with fetuses whose mothers did not have increased glucose levels, fetuses whose mothers had increased glucose levels moved more at 28 to 33 weeks of gestation (P=.031), but not at 34 to 39 (P=.398) and 28 to 39 (P=.238) weeks of gestation. CONCLUSION: Having a meal did not change gross fetal movement counting; however, there are positive correlations between maternal glucose level and gross fetal movement at 28 to 33 weeks of gestation, but not at 34 to 39 weeks of gestation, for both glucose values and value changes under natural conditions of the mother and fetus.

Chlamydia Peritonitis Mimicking Juvenile Carcinomatous Peritonitis Diagnosed by Exploratory Laparoscopy: A Case Report.

Chlamydia trachomatis infections may occur in multiple organs, including the lungs, lymph nodes, peritoneal cavity, and genitourinary systems. This disease results in significant ascites, the swelling of lymph nodes, and elevated tumor markers (CA125), sometimes mimicking an ovarian malignancy. At our hospital, we often perform examination laparoscopic surgery in cases of suspected gynecologic cancers before initial treatment. In this paper, we report the case of a 19-year-old woman who came to our hospital because of an ovarian tumor and ascites. There was no history of sexual intercourse (self-reported). We suspected ovarian cancer from image inspections, so we performed laparoscopic surgery for diagnosis. The final pathological diagnosis was acute-to-chronic inflammation of the bilateral fallopian tubes, and a cytologic examination of the ascites was negative for malignant cells. The C. trachomatis antigen was positive on vaginal examination after the operation. Based on this result, we diagnosed this patient with C. trachomatis infection. Chlamydia peritonitis should be a differential diagnosis for cancer peritonitis in juvenile patients with abnormal ascites. Exploratory laparoscopy should help confirm the pathological diagnosis.

Effect of ritodrine hydrochloride infusion on fetal movement with the use of a fetal movement acceleration measurement recorder (FMAM recorder).

AIM: To investigate the effect of ritodrine hydrochloride infusion on fetal movement. METHOD: We gathered 20 pregnant women who received ritodrine hydrochloride infusion as the treated group, and 147 pregnant women who did not as the control group. All women recorded gross fetal movement with the fetal movement acceleration measurement recorder after 28 gestational weeks. The record was divided into epochs of 10 s, and the ratio of movement-positive epochs to all epochs was calculated as the fetal movement index. Furthermore, the mean duration and the mean number per hour of no-fetal movement period, where the fetus did not move for 5 min or more, were calculated as the indexes of no-fetal movement. All indexes were compared between the two groups at 28-31 and 32-35 gestational weeks. RESULTS: The fetal movement indexes (%) were 17.29 ± 7.46 (mean ± SD) in the control group and 13.65 ± 7.13 in the treated group at 28-31 weeks (p = 0.139). At 32-35 weeks, they were 14.55 ± 6.43 and 18.50 ± 5.33, respectively (p = 0.03). Similarly, the no-fetal movement indexes (min, times/h) were 15.03 ± 10.99 and 1.61 ± 0.88, and 18.70 ± 15.80 and 1.75 ± 0.96 (p = 0.824, and 0.673) at 28-31 weeks. At 32-35 weeks, they were 18.13 ± 10.88 and 1.95 ± 0.97, and 9.20 ± 5.51 and 1.14 ± 0.71, respectively (p = 0.003, and 0.003). CONCLUSION: Ritodrine hydrochloride infusion increased the fetal movement and decreased the no-fetal movement period at 32-35 weeks.

Counting gross fetal movement using a fetal movement acceleration measurement recorder in two fetuses with gastroschisis.

We used the fetal movement acceleration measurement recorder to count gross fetal movement in two fetuses with gastroschisis. In conclusion, both fetuses moved as much as normal fetuses, which suggested that normal fetal movement could indicate reassuring status also in fetuses with malformation when they have normal neurological developments.

A case of adenomyosis with leiomyoma that was effectively treated with relugolix and kamishoyosan add-on therapy.

BACKGROUND: Recently, relugolix, an oral gonadotropin-releasing hormone receptor antagonist, has been considered an effective therapy for leiomyoma based on a phase 3 study in Japanese women. Leiomyoma combined with severe adenomyosis occasionally occurs in perimenopausal women; however, little information on the effectiveness of relugolix against severe adenomyosis exists. CASE PRESENTATION: A 49-year-old woman was referred to our hospital with acute lower abdominal pain and abnormal uterine bleeding. Magnetic resonance imaging revealed multiple leiomyomas with diffuse adenomyosis. Left hydrosalpinx was also observed. The patient refused surgical treatment and preferred oral relugolix. Since she experienced a hot flush and headache induced by relugolix, a traditional Japanese Kampo, kamishoyosan, was added to improve the side effects of relugolix. The patient was asymptomatic at the time of this report and experienced a significant shrinkage in uterine volume. Ultimately, she avoided hysterectomy as desired. CONCLUSIONS: To our knowledge, this is the first report of co-occurring adenomyosis and leiomyoma, which was effectively treated with relugolix. Although the management of adverse side effects, including hot flush and headache by relugolix, has recently attracted attention and controversy, relugolix add-on therapy with kamishoyosan may help treat menopausal symptoms.

Correlation between newborn size and gross fetal movement as counted by a fetal movement acceleration measurement recorder.

The development of the fetal movement acceleration measurement (FMAM) recorder has enabled the accurate counting of gross fetal movements. The aim of the study was to investigate whether gross fetal movement is related to a newborn's size. A total of 90 pregnant women who delivered singleton infant at term were recruited. Gross fetal movements were counted using an FMAM recorder during maternal sleep. The ratio of movement positive 10-s epochs to all epochs during one night was calculated as an index of fetal movement. Independent explanatory variables for the fetal movement index were selected from eight possibilities, that is, maternal age, gestational week, and the six physical measures of the newborn (height, weight, head circumference, chest circumference, Kaup index, and the ratio of head to chest circumference) with the stepwise regression procedure. The selected physical variables and the fetal movement index were analyzed using multiple regression analysis. A total of 2812.95 h from 423 night records were available. Gestational weeks and weight of the newborn were selected as the significant independent variables. Multiple regression analysis revealed that newborn weight had a positive correlation with the fetal movement index (p < 0.0001). The multiple regression equation was "The fetal movement index (%) = 34.9989-0.9088 × gestational weeks + 0.0033 × newborn weight (g)." A person's physical ability and lifetime activity level may originate from fetal health. This study may provide a new way of looking at the Developmental Origins of Health and Disease theory.

Counting fetal movements of small-for-gestational infants using a fetal movement acceleration measurement recorder.

Background: Our purpose was to clarify whether small-for-gestational (SGA) infants is associated with a decrease in fetal movements (FMs) even in the absence of hypoxia. We used a fetal movement acceleration measurement (FMAM) recorder, which enabled counting gross FMs for hours at a time.Methods: (1) Parameters of FMs for 13 women who delivered SGA infants were plotted over normal reference value curves made from 64 normal pregnant women in another study. (2) Linear regression analysis was conducted for the women with SGA infants and the normal pregnant women.Results: Thirty-eight data recordings were available in the SGA group. (1) For the ratio of movement positive 10-s epoch, 14 recordings (36.8%) were below 10% of the normal values. For an average number of movements, 13 (34.2%) were below 10%. Regarding average number, average duration, and longest duration of non-movement period, 12 (31.6%), 13 (34.2%), and 15 records (39.4%) were above 90% of the normal values, respectively. (2) SGA was a factor that decreased the positive epoch ratio and the average movements number, and increased the average number and duration, and the longest duration of non-movement period.Conclusions: SGA is associated with decreased movements even in the absence of hypoxia.

Correlation between umbilical cord length and gross fetal movement as counted by a fetal movement acceleration measurement recorder.

INTRODUCTION: The fetal movement acceleration measurement (FMAM) recorder has made it possible to count gross fetal movements over many hours. Our purpose was to examine the relationship between umbilical cord length and fetal movements as counted by the FMAM recorder. METHODS: Sixty-two pregnant women recorded fetal movements weekly from 28 weeks to term. The ratio of 10-s periods in which movement occurred to total time was calculated as a movement index. Umbilical cord length was measured at delivery. (1) Multiple linear regression analyses were conducted with six explanatory variables (primipara / multipara, anterior / posterior located placenta, placental weight, the mean movement index of 28-31, 32-35, and 36-39 week) and a response valuable (umbilical cord length). (2) All women were divided into groups of shorter, middle, and longer cord length, specifically less than 50 cm, between 50 and 60 cm, and more than 60 cm. The movement index was compared among the three groups at 28-31, 32-35, and 36-39 weeks. RESULTS: A total of 2355.6 h from 368 night records were available. (1) There were no relationships between the cord length and the movement index of 28-31, 32-35, and 36-39 weeks (p = 0.090, 0.235, 0.129, respectively). (2) There were no differences in the movement index among the three groups at 28-31 and 32-35 gestational weeks (p = 0.096, and 0.465, respectively); however, the longer cord group had a greater movement index than the other two groups at 36-39 weeks (p = 0.0008). DISCUSSION: This study suggested that fetal movement near term is an important factor in determining whether cord length becomes relatively longer in normal pregnancies.

Descended marginal sinus of the placenta.

This is the first reported case of descent of the placental marginal sinus through the cervix to the external os. We think marginal sinus rupture does exist. The definition of placental edge should be the parenchyma in diagnosis of low-lying placentation. Clinically, however, the low-lying marginal sinus should be treated similar to low-lying placentation.