Takeshi Kanagawa

A retrospective analysis of ovarian endometriosis during pregnancy

OBJECTIVE To clarify the frequency of pregnancy complicated by ovarian endometriosis and to investigate the size change and outcome of ovarian endometriosis during pregnancy. DESIGN Retrospective study. SETTING Departments of obstetrics and gynecology of the Osaka University and Izumiotsu Municipal Hospitals of Osaka, Japan. PATIENT(S) Women who delivered between 1996 and 2007. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) The frequency of pregnancies complicated by ovarian endometriosis and the size change of the lesions during pregnancy. RESULT(S) The frequency of ovarian endometriosis-complicated pregnancy has almost quadrupled over the last 12 years, to become the most common adnexal mass detected during pregnancy; it was 0.14% (five cases among 3558 deliveries) during the 6-year period from 1996 to 2001, but has increased to 0.52% (19 cases among 3599 deliveries) during the 6-year period from 2002 to 2007, a statistically significant increase of 3.8-fold. Among 25 ovarian endometriotic lesions observed during pregnancy in 24 women (one case had two lesions), the size of the cyst decreased in 13 lesions (52%), went unchanged in 7 (28%), and increased in 5 (20%), that demonstrated decidualization, abscess and rupture. CONCLUSION(S) Ovarian endometriosis during pregnancy can be safely observed conservatively; however, further investigation is required to predict the occurrence of abscess formation or rupture of ovarian endometriosis, and to distinguish the enlargements due to malignant transformation from those related to decidualization.

Post-ischemic hypothermia reduced IL-18 expression and suppressed microglial activation in the immature brain

Inflammation is an important factor for hypoxia-ischemia (HI) brain injury. Interleukin (IL)-18 is a proinflammatory cytokine which may be a contributor to injury in the immature brain after HI. To investigate the effects of post-HI hypothermia on IL-18 in the developing brain, 7-day-old rats were subjected to left carotid artery ligation followed by 8% oxygen for 60 min and divided into a hypothermia group (rectal temperature 32 degrees C for 24 h) and a normothermia group (36 degrees C for 24 h). The IL-18 mRNA was analyzed with real-time RT-PCR, and the protein level was analyzed by Western blot, and the location and source of IL-18 were assessed by immunohistochemistry. The significant increase of the IL-18 mRNA was observed in the ipsilateral hemispheres of the normothermia group at 24 h and 72 h after HI compared with controls, but the level in the ipsilateral hemispheres of the hypothermia group was significantly reduced at both time points, compared with the normothermia group, respectively. The IL-18 protein level in the ipsilateral hemispheres of the normothermia group significantly increased at 72 h after HI compared with controls, however, the protein level of the hypothermia group was significantly decreased, compared with the normothermia group. IL-18-positive cells were observed throughout the entire cortex, corpus callosum (CC) and striatum in the ipsilateral hemispheres of normothermia group at 72 h after HI, however, little positive cells were observed in the hypothermia group. Double labeling immunostaining found that most of the IL-18-positive cells were colocalized with lectin, which is a marker of microglia. The number of ameboid microglia (AM) in the normothermia group was significantly increased in cortex and CC, compared with the number in controls, but there were very few ramified microglia (RM) in these areas. In contrast, the number of AM in the hypothermia group was significantly decreased in cortex and CC, compared with the number in the normothermia group, and there were no significant differences in the number of AM and RM between the hypothermia group and controls. In conclusion, we found that IL-18 mRNA and the protein level were attenuated by post-HI hypothermia and that post-HI hypothermia may decrease microglia activation in the developing brain.

Reliable predictors of neonatal immune thrombocytopenia in pregnant women with idiopathic thrombocytopenic purpura

Of infants born to women with idiopathic thrombocytopenic purpura (ITP), about 10–15% have transient neonatal immune thrombocytopenic purpura (NITP). Of concern is the lack of a reliable predictor for NITP. We conducted a retrospective study of all pregnancies with ITP at Osaka University Hospital over the past 16 years analyzing a total of 127 pregnancies in 88 women with ITP to assess the predictive value of various clinical factors regarding neonatal platelet count in the current pregnancy. We also reviewed the literature concerning ITP in pregnancy and NITP prediction. Neonatal platelet counts were less than 100 × 109/L in 20 of 130 neonates (15.4%), less than 50 × 109/L in 11 neonates (8.5%), and less than 20 × 109/L in three neonates (2.3%). There was a strong correlation between the first and second sibling regarding the occurrence and the severity of NITP with Spearman correlation coefficient of 0.55 (P = 0.001) at birth and 0.63 (P < 0.0001) at nadir after birth. A maternal platelet count less than 100 × 109/L at delivery showed a statistical trend for an association with the occurrence of NITP (P = 0.043). Moreover, maternal ITP refractory to splenectomy correlated with a higher risk for fetal or neonatal ICH according to the review of the literature. In conclusion, pregnant women who have had a previous offspring with NITP or who have ITP refractory to splenectomy may be at particular risk of delivering an offspring with significant NITP. Management decisions, including mode of delivery, may be altered by the degree of risk for potentially severe NITP. Am. J. Hematol., 2012.

Central aortic blood pressure and augmentation index during normal pregnancy

The current study tested the hypothesis that pregnancy-related changes are more pronounced in central hemodynamics, and both central aortic systolic blood pressure (cSBP) and augmentation index (AIx) are independent from brachial systolic blood pressure (bSBP) in normal pregnant subjects. In 830 healthy pregnant women from 12 to 36 weeks gestation, we measured cSBP and AIx-75 (AIx at heart rate of 75 beats per minute) non-invasively by pulse waveforms of the radial artery using an automated applanation tonometric system. In 69 pregnant women, we recorded these data longitudinally. cSBP and AIx-75 significantly declined during pregnancy, reaching its nadir in mid-pregnancy and rising towards term. Pregnancy-related changes were more pronounced in AIx-75 compared with cSBP, but less evident in bSBP. AIx-75, but not cSBP, was independent from bSBP throughout pregnancy. cSBP and AIx-75, but not bSBP, were significantly increased in healthy pregnant women older than 35 years. This study established normal values for pulse wave analysis parameters throughout pregnancy, and indicated that pulse wave analysis might offer additional and independent information about maternal arterial compliance to conventional brachial blood pressure measurements. These data may be used as the basis for further investigation into the role of pulse wave analysis in the assessment, management and prediction of disorders, which might interfere with pregnancy-related cardiovascular adaptations.

Nicotine restores endothelial dysfunction caused by excess sFlt1 and sEng in an in vitro model of preeclamptic vascular endothelium: a possible therapeutic role of nicotinic acetylcholine receptor (nAChR) agonists for preeclampsia.

OBJECTIVE In this study we tested the hypothesis that nicotine restores proangiogenic functions to endothelial cells pretreated with soluble fms-like tyrosine kinase 1 and/or soluble endoglin. STUDY DESIGN Wound healing assay and tube formation assay were performed using human umbilical vein endothelial cells treated with nicotine (10(-9) to 10(-6) M), and with various combinations of soluble fms-like tyrosine kinase 1 (100 ng/mL), soluble endoglin (100 ng/mL), and nicotine (10(-7) M). Enzyme-linked immunosorbent assay was performed to measure vascular endothelial growth factor, placental growth factor, and transforming growth factor-beta1 concentrations in the conditioned media treated with nicotine (10(-9) to 10(-6) M). RESULTS Nicotine significantly facilitated endothelial migration and tube formation. By contrast, soluble fms-like tyrosine kinase 1 and/or soluble endoglin suppressed these endothelial functions. Nicotine restored these soluble fms-like tyrosine kinase 1 and/or soluble endoglin-reduced endothelial functions. Placental growth factor, but not transforming growth factor-beta1, production was significantly stimulated by the presence of nicotine. Vascular endothelial growth factor was undetectable. CONCLUSION Our results suggest a possible mechanism for the protective effects of cigarette smoking against preeclampsia, thus proposing a therapeutic potential of nicotine or other nicotinic acetylcholine receptor agonists for preeclampsia.

Spinal subarachnoid hematoma following spinal anesthesia in a patient with HELLP syndrome

A case of subarachnoid hematoma following spinal anesthesia for cesarean section in a patient with HELLP syndrome is reported. A 39-year-old woman underwent cesarean section under spinal anesthesia for worsening preeclampsia with HELLP syndrome. Despite full recovery from the spinal anesthetic, on the second postoperative day she felt numbness on the posterior aspect of her right leg, noticed she was insensitive to bladder fullness and had mild flaccid paraparesis. Magnetic resonance imaging revealed a spinal subarachnoid hematoma with cauda equina compression. With conservative management she made an almost complete recovery within three months. Serial magnetic resonance imaging showed spontaneous regression of the hematoma. The risk of spinal subarachnoid hematoma following obstetric regional anesthesia is exceedingly small even in a patient with coagulopathy and, to our knowledge, this is only the second reported case following obstetric regional anesthesia. Anesthesia for HELLP syndrome in patients with an adequate platelet count but without disseminated intravascular coagulation is controversial. It is therefore important for clinicians to recognize the symptoms and signs of spinal subarachnoid hematoma to avoid delay in treatment that might result in severe neurological deficit.

Mid-second trimester measurement of fetal nasal bone length in the Japanese population.

Aim:  We carried out a preliminary study to compare the nasal bone length (NBL) and biparietal diameter/NBL (BPD/NBL) ratio between the Japanese and white populations.

A decrease of cell proliferation by hypothermia in the hippocampus of the neonatal rat

Hypothermia is a potential therapy for cerebral hypoxic ischemic injury of not only adults but also neonates. However, the side effects of hypothermia in the developing brain, where a massive amount of neurogenesis occurs, remain unclear. We investigated the proliferation of neural progenitor cells by systemic application of the thymidine analog 5-bromodeoxyuridine (BrdU) in neonatal rats in a severe hypothermic environment. The rat pups were divided into two groups, a hypothermia group (30 degrees C: n=10) and a normothermia group (37 degrees C: n=10). After the pups were placed for 21 h in each environment, 100 mg/kg/day of BrdU was injected intraperitoneally to label dividing cells, and then the pups were sacrificed at 24 h. We examined the number of BrdU-labeled cells in the subventricular zone of the periventricle and the subgranular zone of the dentate gyrus. In the hypothermic environment, BrdU-labeled cells significantly decreased in number in the dentate gyrus, but not in the periventricular region. Thus, the severe hypothermic environment induced a decrease of neurogenesis in the neonatal rat. These observations are noteworthy regarding clinical hypothermia therapy following cerebral hypoxic ischemic injury during the perinatal period.

Balloon tamponade during cesarean section is useful for severe post-partum hemorrhage due to placenta previa

Aim:  Severe post‐partum hemorrhage during cesarean section due to placenta previa is still one of the leading causes of maternal mortality. The aim of this study was to evaluate the efficiency of intrauterine tamponade with a Sengstaken‐Blakemore tube (SB‐tube) for the treatment of severe post‐partum hemorrhage in cases of placenta previa.

Oxidative stress-induced S100B protein from placenta and amnion affects soluble Endoglin release from endothelial cells.

Oxidative stress with elevated intracellular Ca(2+) concentration as well as endothelial dysfunction is a component of pre-eclampsia. Our aim was to investigate the oxidative stress-dependent expression of Endoglin and Ca(2+)-binding S100B protein from villous and amniotic tissue cultures, and to assess sEng expression from S100B protein-stimulated endothelial cells. We initially examined Endoglin and Hydroxy-nonenal-(HNE)-modified proteins in the placentas and amnion obtained from women with pre-eclampsia (n = 8), and healthy controls (n = 8) by immunohistochemistry. To examine oxidative stress and the S100B protein effect on sEng expression from endothelial cells, normal villous and amniotic tissue cultures were stimulated by 4-HNE, sodium fluoride and xanthine/xanthine oxidase, whereas human umbilical vein endothelial cell cultures were treated with S100B protein in a dose- and time-dependent manner at 37 degrees C in an environment of 95% air and 5% of CO(2). Culture supernatants were assessed using ELISA. Cell viability was determined using MTS assay. The concentrations of sEng and S100B protein were significantly increased in the villous and amniotic tissue culture supernatants under oxidative stress. S100B protein-stimulated endothelial cells released sEng into conditioned media with a significantly higher expression levels at a concentration of 200 pM-20 nM S100B by 2 h, whereas treated with 200 nM of S100B endothelial cells significantly expressed sEng by 12 h and stimulated the cell proliferation by the same period of time. Our findings show that oxidative stress affects sEng and S100B protein expression from villous and amniotic tissues, and picomolar and low nanomolar concentrations of S100B protein significantly up-regulate sEng release from endothelial cells leading to endothelial dysfunction.