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1.
J Perinat Med ; 2020 Apr 09.
Article in English | MEDLINE | ID: mdl-32284451

ABSTRACT

Background There are numerous significant physiological changes occurring in circulation during labor. To detect these rapid hemodynamic changes, invasive and intermittent measurement techniques are not reliable. To suggest a suitable delivery method for pregnancy with cardiac disease, this study analyzed how each delivery method influences cardiac function using a noninvasive and continuous measurement technique. Methods A prospective study was accomplished at the National Cerebral and Cardiovascular Center in Japan from October 1, 2014, to November 30, 2018. The classification of the healthy heart pregnant women was according to the delivery method: vaginal delivery (VD) without epidural anesthesia, VD with epidural anesthesia, and caesarean section (CS). The hemodynamic parameters cardiac index (CI), stroke volume index (SI), and heart rate (HR) were evaluated regularly throughout delivery by noninvasive electrical cardiometry monitor. Results Ten cases were examined for each group. CI and HR were significantly increased before VD, while the increase in CI and HR was mild in the epidural group in comparison to the nonepidural group. SI was increased toward the delivery in the epidural group, and it was constant in the nonepidural group. However, there was no alteration in the level of outcomes of the two groups. In CS, SI increased and HR decreased before delivery. After delivery, SI continued to increase, while HR did not change but CI increased. Conclusion In VD, the increase in venous circulation according to the autotransfusion is managed by increasing HR. By epidural anesthesia, the increase in HR was suppressed and SI was increased. However, as epidural anesthesia increases the vascular capacity, the level of SI outcome was comparable. In CS, the HR was decreased because of the spinal anesthesia and the SI was increased because of many factors like hydration. As there are many factors to control in CS, VD with epidural anesthesia will be the first preference for most cardiac patients.

2.
Pediatr Cardiol ; 40(6): 1134-1143, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31087143

ABSTRACT

The effect of pregnancy on aortic root in women with repaired conotruncal anomalies (CTA) has not been clarified. This study examined aortic diameters during and after pregnancy in women with repaired CTA. A retrospective review of consecutive pregnant women with repaired CTA was performed for results of echocardiography from 1 year before pregnancy to 3 years after delivery and compared with findings from healthy pregnant volunteers. Participants comprised 42 subjects and 49 deliveries with repaired CTA (CTA group), and 47 healthy pregnant women (control group). Although no maternal aortic events were encountered, aortic diameters during pregnancy increased by 1.0 ± 2.2 mm (maximum, 7.0 mm) in the CTA group and 0.6 ± 1.3 mm (maximum, 3.4 mm) in the control group (p = 0.13). The CTA subgroup with increase in aortic diameter ≥ 3.5 mm during pregnancy showed no reversion to baseline diameter at follow-up > 6 months after delivery. Significant risk factors for increased aortic diameter and no reversal included pulmonary atresia, history of aortopulmonary shunt, older age at repair, and smaller left ventricular end-diastolic diameter pre-pregnancy. Women with repaired CTA tolerated pregnancy and delivery well. However, the aortic root progressively dilated during pregnancy and 1/4 of them, especially those with longstanding high aortic blood flow before repair, showed an increase of aortic root size of ≥ 3.5 mm during the peripartum period; this dilatation tended not to revert to the pre-pregnancy diameter. Therefore, serial measurement of the aortic root during pregnancy and after delivery is recommended in these women.


Subject(s)
Aorta/pathology , Aortic Valve/pathology , Sinus of Valsalva/pathology , Adult , Age Factors , Aorta/abnormalities , Aorta/diagnostic imaging , Aortic Valve/abnormalities , Aortic Valve/diagnostic imaging , Case-Control Studies , Computed Tomography Angiography , Delivery, Obstetric/adverse effects , Dilatation, Pathologic/etiology , Echocardiography , Female , Heart Defects, Congenital/surgery , Humans , Imaging, Three-Dimensional , Magnetic Resonance Imaging , Male , Pregnancy , Pulmonary Atresia/etiology , Retrospective Studies , Risk Factors , Sinus of Valsalva/diagnostic imaging , Time Factors
3.
J Cardiol ; 74(4): 347-352, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31060956

ABSTRACT

BACKGROUND: Women with complete atrioventricular block (CAVB) can tolerate hemodynamic changes during pregnancy; however, the incidence of cardiac events in women with CAVB may increase after delivery. The aim of this study was to investigate predictive factors for postpartum cardiac events in pregnant women with CAVB. METHODS AND RESULTS: Pregnant women with CAVB who received perinatal management at a tertiary cardiac center from 1981 to 2015 were retrospectively reviewed. Univariate and multivariate logistic analyses of postpartum cardiac events were performed. Postpartum cardiac event was defined as cardiopulmonary arrest, cardiac failure, or the need for permanent pacemaker implantation (p-PMI) within 3 months after delivery. A total of 63 pregnancies in 36 women with CAVB were included in this study; 25 had undergone p-PMI before pregnancy. Regardless of p-PMI status, women with CAVB had no further increases in heart rate during the second and third trimesters. No heart failure was found during pregnancy and delivery. Postpartum cardiac events occurred in 9 pregnancies (14.3%) in 8 women with CAVB; 3 had cardiac failure and p-PMI, 3 had cardiac failure, 2 required p-PMI, and 1 had cardiopulmonary arrest. Multivariate analysis showed that perinatal ventricular pause (odds ratio 11.60, 95% confidence interval 1.90-82.18, p<0.01) and family history of CAVB (odds ratio 10.59, 95% confidence interval 1.36-90.56, p=0.03) were associated with postpartum cardiac events. CONCLUSIONS: All cardiac events occurred during the postpartum period among women with CAVB, and ventricular pause during the perinatal period and a family history of CAVB were predictors of postpartum cardiac events. Close follow-up should be considered during the postpartum period for women with high-risk CAVB.


Subject(s)
Atrioventricular Block/complications , Heart Arrest/epidemiology , Heart Failure/epidemiology , Pregnancy Complications, Cardiovascular/epidemiology , Puerperal Disorders/epidemiology , Adult , Atrioventricular Block/physiopathology , Female , Heart Arrest/etiology , Heart Failure/etiology , Heart Rate , Humans , Incidence , Multivariate Analysis , Odds Ratio , Pacemaker, Artificial/statistics & numerical data , Postpartum Period/physiology , Pregnancy , Pregnancy Complications, Cardiovascular/etiology , Pregnancy Complications, Cardiovascular/physiopathology , Puerperal Disorders/etiology , Retrospective Studies , Young Adult
4.
Pediatr Cardiol ; 40(4): 865-870, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30830281

ABSTRACT

The frequency of newborns with congenital heart disease (CHD) is approximately 1% in the general population; however, the recurrence rate of CHD in mothers with CHD differs in ethnicity and reports. We therefore aimed to determine the prevalence of CHD among neonates born to mothers with CHD in our institute in Japan. We reviewed the medical charts of 803 neonates delivered by 529 women with CHD at the National Cerebral and Cardiovascular Center from 1982 to 2016. They included isolated ventricular septal defect (VSD,31.4%), isolated atrial septal defect (ASD, 23.3%), tetralogy of Fallot (TOF,10.6%). We defined CHD in neonates as being diagnosed within 1 month of birth. We estimated that the average rate of the CHD recurrence was 3.1%. The recurrence ratios in each maternal CHD were 8.6%, 7.1%, 6.2%, 4.8%, 3.6%, and 1.5% for PS, CoA, TOF, atrioventricular septal defect, VSD, and ASD, respectively. The rate of CHD in offsprings whose mothers have CHD was 3 times greater than that of mothers with healthy hearts. Almost half of neonates with CHD had the same phenotype as their mother in our series. Especially, PS and CoA were closely related to the type of maternal CHD.


Subject(s)
Heart Defects, Congenital/epidemiology , Adolescent , Adult , Child , Female , Heart Defects, Congenital/etiology , Humans , Infant, Newborn , Japan , Male , Middle Aged , Mothers/statistics & numerical data , Prevalence , Recurrence , Retrospective Studies , Young Adult
5.
J Comput Assist Tomogr ; 43(1): 104-108, 2019.
Article in English | MEDLINE | ID: mdl-30119066

ABSTRACT

OBJECTIVE: We attempted to evaluate fetal cardiac activity of congenital heart disease (CHD) and normal heart fetuses by magnetic resonance imaging (MRI). METHODS: We evaluated the fetal cardiac functional assessment and the blood flow of descending aorta at 34 weeks' gestation or more by MRI and compared the results with ultrasonography findings. We measured 6 normal heart fetuses and 14 CHD fetuses. RESULTS: The ejection fraction (EF) and descending aorta blood flow in the CHD group were 76.4% ± 11.9%, 687.5 ± 303.8 mL/min by ultrasonography and 48.3% ± 7.1%, 711.4 ± 273.1 mL/min by MRI; those in the normal group were 66.9% ± 12.2%, 898.1 ± 245.9 mL/min by ultrasonography and 51.3% ± 4.2%, 911.9 ± 223.1 mL/min by MRI. CONCLUSIONS: There was no significant difference in descending aorta blood flow measurements between ultrasonography and MRI, but the EF showed a significant between-group difference. In the normal group, the variation of EF and blood flow measured by MRI was significantly smaller compared with those of ultrasonography.


Subject(s)
Fetal Heart/diagnostic imaging , Heart Defects, Congenital/diagnostic imaging , Magnetic Resonance Imaging/methods , Prenatal Diagnosis/methods , Adult , Female , Fetal Heart/embryology , Fetal Heart/physiopathology , Heart Defects, Congenital/embryology , Heart Defects, Congenital/physiopathology , Humans , Japan , Pregnancy , Prospective Studies
6.
J Obstet Gynaecol Res ; 45(2): 382-388, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30259601

ABSTRACT

AIM: We sought to examine the safety and efficacy of a 52-mg levonorgestrel-releasing intrauterine system (LNG-IUS), and to evaluate the changes in biomarkers of infection, anemia and cardiovascular conditions after LNG-IUS insertion in women with cardiovascular disease. METHODS: We prospectively followed women with a cardiovascular disease in whom a 52-mg LNG-IUS was inserted between 2009 and 2015. The primary outcome was the frequency of cardiovascular and gynecologic side effects due to the LNG-IUS over the year after LNG-IUS insertion. The secondary outcomes were the changes in menstrual blood loss and biomarkers, e.g., white blood cell count and the levels of C-reactive protein, hemoglobin and brain natriuretic peptide. We also evaluated the 24-month continuation rate of LNG-IUS. RESULTS: A total of 34 women were prospectively followed-up, including two women with pulmonary hypertension. No cardiovascular side effects were identified during the 1 year after LNG-IUS insertion, other than one case of mild vasovagal reaction at insertion. Neither the white blood cell count nor the C-reactive protein value increased after LNG-IUS insertion. The menstrual blood loss was decreased in most subjects and the median hemoglobin levels increased significantly within 1 year after insertion (P < 0.001 and P = 0.002). Moreover, brain natriuretic peptide levels tended to decrease in correspondence with the hemoglobin elevation (P = 0.074). The 24-month LNG-IUS continuation rate was 97% (95% confidence interval 85-100). CONCLUSION: No clinically significant cardiovascular event was identified during the 1 year after 52-mg LNG-IUS insertion among women with cardiovascular disease. The 52-mg LNG-IUS may have specific favorable effects by decreasing the risk of iron deficiency anemia in these women.


Subject(s)
Cardiovascular Diseases/blood , Contraceptive Agents, Female/pharmacology , Intrauterine Devices, Medicated , Levonorgestrel/pharmacology , Adult , Cardiovascular Diseases/chemically induced , Contraceptive Agents, Female/administration & dosage , Contraceptive Agents, Female/adverse effects , Female , Follow-Up Studies , Humans , Intrauterine Devices, Medicated/adverse effects , Levonorgestrel/administration & dosage , Levonorgestrel/adverse effects
7.
J Cardiol ; 73(3): 247-254, 2019 03.
Article in English | MEDLINE | ID: mdl-30579805

ABSTRACT

OBJECTIVE: Arterial switch operation (ASO) for dextro-transposition of the great arteries (d-TGA) has gradually replaced the atrial switch operation and has become the standard operation. To date, the outcomes of pregnant women with d-TGA after this new operation have not been investigated. In this study, we investigated the impact of ASO on pregnant outcomes and mid-term prognosis in women with d-TGA and compared with the atrial switch operation through the literature review. METHODS AND RESULTS: There were 20 pregnancies in 10 women with d-TGA after ASO and 6 resulted in abortion. Among 14 successful pregnancies in 10 women, 11 pregnancies achieved the term delivery and 3 pregnancies, including 1 twin pregnancy, resulted in preterm labor. Maternal cardiovascular events occurred in 4 (heart failure and arrhythmias in 3 and arrhythmia in 1), and all were controllable with medications. Risk factors for the peripartum cardiac events were older age at ASO and delivery, and higher concentration of brain natriuretic peptide (BNP) at first trimester (p<0.05). In 7-60 month-follow-up after delivery, no case showed deterioration of functional class and systemic ventricular function. According to the literature review, women after ASO demonstrated a better prognosis than those after the atrial switch operation. CONCLUSIONS: The majority of women with d-TGA after ASO tolerated pregnancy and delivery well. The older age at ASO, an elderly pregnancy, and higher BNP levels at the first trimester were possibly risk factors of peripartum cardiovascular events among the group. The literature reviews and this study may indicate the advantage of systemic left ventricle compared with systemic right ventricle in long-term outcomes after delivery.


Subject(s)
Arterial Switch Operation/statistics & numerical data , Pregnancy Complications, Cardiovascular/surgery , Pregnancy Outcome/epidemiology , Transposition of Great Vessels/surgery , Adult , Arterial Switch Operation/methods , Female , Humans , Infant, Newborn , Pregnancy , Risk Factors , Tertiary Care Centers , Treatment Outcome
8.
Int Heart J ; 59(4): 862-867, 2018 Jul 31.
Article in English | MEDLINE | ID: mdl-29794382

ABSTRACT

Little is known about pregnancies of left ventricular noncompaction cardiomyopathy (LVNC), much less cases in which LVNC was definitively diagnosed prepregnancy. We report the cases of three pregnant Japanese women definitively diagnosed with LVNC prepregnancy. Case 1 presented LVNC with restrictive phenotype. Her pregnancy was terminated due to exacerbated pulmonary hypertension and low output status at 30 weeks' gestation. Case 2 presented isolated LVNC with nonsustained ventricle tachycardia. A cesarean section was performed at 36 weeks' gestation because of placenta previa. Case 3 presented dilated LVNC. Labor induction was performed because of decreased left ventricular ejection fraction, leading to a vaginal delivery at 37 weeks' gestation. In all cases, no thromboembolic event was identified during pregnancy; two patients received anticoagulants. We reviewed all English-literature cases of pregnant women definitively diagnosed with LVNC prepregnancy to analyze causes of adverse pregnancy outcomes and the necessity of anticoagulation. Four of the six pregnancies identified were terminated due to exacerbated cardiomyopathy phenotypes and not complications due to noncompaction itself, resulting in three cases' preterm deliveries. No thromboembolic event was identified by maintenance of the anticoagulation strategy determined prepregnancy. In pregnancies with LVNC, the possibility of a severe cardiac event and the indications for termination of the pregnancy can depend on the cardiomyopathy phenotypes, not noncompaction itself. Anticoagulation only because of the pregnancy itself may be redundant. In the management of LVNC during pregnancy, close monitoring of the condition of different phenotypes and reassessment of the necessity of anticoagulation can contribute to the pregnancy outcome.


Subject(s)
Anticoagulants/administration & dosage , Isolated Noncompaction of the Ventricular Myocardium , Pregnancy Complications, Cardiovascular , Thromboembolism/prevention & control , Adult , Cesarean Section/methods , Female , Humans , Hypertension, Pulmonary/diagnosis , Hypertension, Pulmonary/etiology , Isolated Noncompaction of the Ventricular Myocardium/complications , Isolated Noncompaction of the Ventricular Myocardium/diagnosis , Isolated Noncompaction of the Ventricular Myocardium/physiopathology , Labor, Induced/methods , Patient Care Management/methods , Pregnancy , Pregnancy Complications, Cardiovascular/diagnosis , Pregnancy Complications, Cardiovascular/physiopathology , Pregnancy Complications, Cardiovascular/therapy , Pregnancy Outcome , Tachycardia, Ventricular/diagnosis , Tachycardia, Ventricular/etiology , Thromboembolism/etiology , Ventricular Dysfunction, Left/diagnosis , Ventricular Dysfunction, Left/etiology
9.
Int Heart J ; 59(2): 435-438, 2018 Mar 30.
Article in English | MEDLINE | ID: mdl-29445057

ABSTRACT

Recently, implantable cardioverter-defibrillators (ICD) have become capable of monitoring intrathoracic impedance to detect an increased fluid volume and heart failure. Pregnancy is a well-known cause of an increased body fluid volume; however, it is not clear whether the measurement of intrathoracic impedance by ICD is clinically useful for precisely detecting heart failure in pregnant women. We herein report the case of a 39-year-old woman with an ICD that had been implanted after an event of ventricular fibrillation due to severe aortic regurgitation with a bicuspid aortic valve. Elevated right ventricular pressure and brain natriuretic peptide levels were detected at 37 weeks of gestation and postpartum. At the same time, the ICD's stored fluid index gradually increased and exceeded the threshold on the 10th day after delivery. She was treated with diuretics and recovered from postpartum heart failure. The physiological volume changed in the perinatal period, but we were still able to detect heart failure by ICD. Intrathoracic impedance monitoring is effective in the perinatal field.


Subject(s)
Defibrillators, Implantable , Electric Impedance , Heart Failure/diagnosis , Pregnancy Complications, Cardiovascular/diagnosis , Ventricular Fibrillation/therapy , Adult , Female , Humans , Peripartum Period , Pregnancy , Water-Electrolyte Balance/physiology
10.
Pregnancy Hypertens ; 10: 46-50, 2017 Oct.
Article in English | MEDLINE | ID: mdl-29153689

ABSTRACT

OBJECTIVES: Pregnancy can be well tolerated after the repair of aortic coarctation. However, a higher incidence of hypertensive disorders during these pregnancies was reported. We analyzed the perinatal changes in echocardiographic parameters in women with aortic coarctation and investigated the risk factors of gestational hypertension (GH). METHODS: We retrospectively identified 15 pregnancies in nine Japanese women with aortic coarctation between 1982 and 2015. We categorized the patients according to the presence/absence of GH as the group with GH(n=3) and that without GH(n=12). The echocardiographic parameters were compared between groups. RESULTS: Our analysis revealed that a pre-pregnancy Doppler-measured pressure gradient≥20mmHg and a left ventricular mass index≥95g/m2 were significant risk factors for GH. The left ventricular end-diastolic diameters at the first and the third trimesters, the left ventricular end-systolic diameters at the first trimester, and the left ventricular ejection fraction at the third trimester were also significantly higher in the pregnancies with GH. All of these findings had been obtained before the patients' GH occurred. CONCLUSIONS: Hypertrophy of the left ventricle with a lower ejection fraction and a high pressure gradient across the coarctation were risk factors for GH in the patients with aortic coarctation. Thus, serial measurements using echocardiography are important for predicting GH in women with aortic coarctation. However, further research investigating this finding with a larger sample size is needed.


Subject(s)
Aortic Coarctation , Hypertension, Pregnancy-Induced/diagnosis , Pregnancy Complications, Cardiovascular , Ultrasonography, Prenatal , Adult , Echocardiography, Doppler , Female , Humans , Hypertension, Pregnancy-Induced/diagnostic imaging , Hypertension, Pregnancy-Induced/physiopathology , Pre-Eclampsia/diagnosis , Pre-Eclampsia/diagnostic imaging , Pre-Eclampsia/physiopathology , Pregnancy , Pregnancy Trimester, First
11.
J Obstet Gynaecol Res ; 43(10): 1629-1633, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28691228

ABSTRACT

Pregnancy with Marfan syndrome (MFS) presents challenges to the clinician because of the increased incidence of maternal cardiovascular complications, including acute aortic dissection (ADD) and the involvement of the fetus owing to the urgency of the need for surgery and the low likelihood of survival with premature delivery. Patient 1 was a 36-year-old pregnant Japanese woman with MFS who was referred at 16 gestational weeks with aortic root diameter 35.1 mm. Stanford type B AAD occurred on delivery without evident blood pressure changes. Patient 2 was a 31-year-old pregnant Japanese woman with MFS with aortic root diameter 28.3 mm at 20 gestational weeks after David procedure. Ultimately fatal Stanford type B AAD occurred on post-partum day 15. Both patients were treated with beta-blockers when AAD occurred. Although these two patients were initially considered to have relatively low risk according to previous reports and guidelines, AAD occurred. It is very important to provide information about these high pregnancy risks to women with MFS before conception, and to follow MFS pregnancies with great caution.


Subject(s)
Adrenergic beta-Antagonists/pharmacology , Aortic Aneurysm , Aortic Dissection , Marfan Syndrome/complications , Pregnancy Complications, Cardiovascular , Adult , Aortic Dissection/drug therapy , Aortic Dissection/etiology , Aortic Aneurysm/drug therapy , Aortic Aneurysm/etiology , Female , Humans , Pregnancy , Pregnancy Complications, Cardiovascular/drug therapy , Pregnancy Complications, Cardiovascular/etiology
12.
Circ J ; 80(10): 2221-6, 2016 Sep 23.
Article in English | MEDLINE | ID: mdl-27593227

ABSTRACT

BACKGROUND: The effects of ß-adrenergic blockers on the fetus are not well understood. We analyzed the maternal and neonatal outcomes of ß-adrenergic blocker treatment during pregnancy to identify the risk of fetal growth restriction (FGR). METHODS AND RESULTS: We retrospectively reviewed 158 pregnancies in women with cardiovascular disease at a single center. Maternal and neonatal outcomes were analyzed in 3 categories: the carvedilol (α/ß-adrenergic blocker; α/ß group, n=13); ß-adrenergic blocker (ß group, n=45), and control groups (n=100). Maternal outcome was not significantly different between the groups. FGR occurred in 1 patient (7%) in the α/ß group, in 12 (26%) in the ß group, and in 3 (3%) in the control group; there was a significant difference between the incidence of FGR between the ß group and control group (P<0.05). The ß group included propranolol (n=22), metoprolol (n=12), atenolol (n=6), and bisoprolol (n=5), and the individual incidence of FGR with these medications was 36%, 17%, 33%, and 0%, respectively. CONCLUSIONS: As a group, ß-adrenergic blockers were significantly associated with FGR, although the incidence of FGR varied with individual ß-blocker. Carvedilol, an α/ß-adrenergic blocker, had no association with FGR. More controlled studies are needed to fully establish such associations. (Circ J 2016; 80: 2221-2226).


Subject(s)
Adrenergic beta-Antagonists/adverse effects , Fetal Growth Retardation/chemically induced , Pregnancy Complications, Cardiovascular/drug therapy , Adrenergic beta-Antagonists/administration & dosage , Adult , Female , Fetal Growth Retardation/physiopathology , Humans , Pregnancy , Pregnancy Complications, Cardiovascular/physiopathology , Retrospective Studies , Risk Factors
13.
PLoS One ; 10(4): e0123712, 2015.
Article in English | MEDLINE | ID: mdl-25876079

ABSTRACT

OBJECTIVES: Induction of the immune response is a major problem in replacement therapies for inherited protein deficiencies. Tolerance created in utero can facilitate postnatal treatment. In this study, we aimed to induce immune tolerance towards a foreign protein with early gestational cell transplantation into the chorionic villi under ultrasound guidance in the murine model. METHODS: Pregnant C57BL/6 (B6) mice on day 10 of gestation were anesthetized and imaged by high resolution ultrasound. Murine embryos and their placenta were positioned to get a clear view in B-mode with power mode of the labyrinth, which is the equivalent of chorionic villi in the human. Bone marrow cells (BMCs) from B6-Green Fluorescence Protein (B6GFP) transgenic mice were injected into the fetal side of the placenta which includes the labyrinth with glass microcapillary pipettes. Each fetal mouse received 2 x 105 viable GFP-BMCs. After birth, we evaluated the humoral and cell-mediated immune response against GFP. RESULTS: Bone marrow transfer into fetal side of placenta efficiently distributed donor cells to the fetal mice. The survival rate of this procedure was 13.5%(5 out of 37). Successful engraftment of the B6-GFP donor skin grafts was observed in all recipient (5 out of 5) mice 6 weeks after birth. Induction of anti-GFP antibodies was completely inhibited. Cytotoxic immune reactivity of thymic cells against cells harboring GFP was suppressed by ELISPOT assay. CONCLUSIONS: In this study, we utilized early gestational placental injection targeting the murine fetus, to transfer donor cells carrying a foreign protein into the fetal circulation. This approach is sufficient to induce both humoral and cell-mediated immune tolerance against the foreign protein.


Subject(s)
Bone Marrow Transplantation , Chorionic Villi , Fetus/immunology , Immune Tolerance/immunology , Placenta/transplantation , Skin Transplantation , Animals , Cell Transplantation , Female , Green Fluorescent Proteins/metabolism , Humans , Mice , Mice, Inbred C57BL , Pregnancy , Tissue Donors
14.
Circ J ; 78(10): 2501-6, 2014.
Article in English | MEDLINE | ID: mdl-25099604

ABSTRACT

BACKGROUND: The influence of the physiological circulatory changes during pregnancy on hypertrophic cardiomyopathy (HCM) is unclear. There have been no comprehensive studies of pregnant women with HCM in the Japanese population. METHODS AND RESULTS: A total of 27 pregnancies (23 women with HCM) were retrospectively reviewed. A total of 18 cardiovascular events occurred in 13 of the 27 pregnancies (48%), and 13 of these events (76%) were related to arrhythmia. The cardiovascular events tended to occur in the early stage of pregnancy (≈30 gestational weeks) or postpartum. The events related to arrhythmia mainly occurred in the early stage of pregnancy or at approximately 30 gestational weeks. Four pregnancies were terminated because of cardiovascular events. Cardiovascular events occurred in 8 of 9 pregnancies in women on medication before pregnancy (88%), 7 of 10 pregnancies with high CARPREG score (70%), and in 9 of 12 pregnancies with high ZAHARA score (75%). CONCLUSIONS: Cardiovascular events occurred in more than half of the pregnant women complicated with HCM, and the arrhythmia is the most common cardiovascular event. Medication in the pre-pregnancy period, and CARPREG or ZAHARA score ≥1 were identified as risk factors of cardiac events during pregnancy or postpartum.


Subject(s)
Arrhythmias, Cardiac/epidemiology , Cardiomyopathy, Hypertrophic/epidemiology , Pregnancy Complications, Cardiovascular/epidemiology , Pregnancy Trimester, First , Adult , Arrhythmias, Cardiac/drug therapy , Cardiomyopathy, Hypertrophic/drug therapy , Female , Humans , Japan/epidemiology , Pregnancy , Pregnancy Complications, Cardiovascular/drug therapy , Risk Factors
15.
Int J Hematol ; 97(4): 491-7, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23456264

ABSTRACT

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired stem cell disorder characterized by intravascular hemolysis and thrombosis. The most serious complication is thrombosis, the risk of which is augmented by the hyper-coagulable state that occurs during pregnancy; despite this risk, however, young female PNH patients often desire to have a baby. We recently experienced two successful deliveries in PNH patients, who were treated with anticoagulant therapy during their pregnancies. Meanwhile, given the potential benefit of eculizumab (Soliris), a humanized monoclonal antibody against C5, in reducing thrombosis and hemolysis, it represents a promising therapeutic option for the treatment of pregnant PNH patients in combination with, or in replacement of, anticoagulant therapy.


Subject(s)
Anticoagulants/therapeutic use , Hemoglobinuria, Paroxysmal/drug therapy , Adult , Antibodies, Monoclonal, Humanized/therapeutic use , Female , Hemoglobinuria, Paroxysmal/diagnosis , Heparin, Low-Molecular-Weight/analogs & derivatives , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Pregnancy , Pregnancy Outcome , Treatment Outcome
16.
Congenit Anom (Kyoto) ; 53(1): 9-17, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23480353

ABSTRACT

Unrecognizable exposure to estrogenic substance may cause estrogen-dependent diseases, endometriosis and cancer. Pregnant mice (ICR/Jcl, CLEA) were exposed to 0.01 mg ethinyl estradiol (EE2 )/kg per day or vehicle (olive oil) through oral intubation from day 11 to 17 of gestation. They delivered their offspring and raised them. When the experimental female F1 mice were at 8 weeks of age, they were not exposed to EE2 or to the same dose of EE2 or to vehicle twice a week until 20 weeks of age. The control female F1 mice were exposed to the same dose of EE2 or vehicle alone, similarly. All mice were killed at 28 weeks of age. The resected uteri and ovaries were processed for microscopic examinations and for determination of the aromatase mRNA levels and aromatase protein through quantitative RT-PCR and Western blotting, respectively. Adenomyosis and adenocarcinomatous changes were significantly discernible in the EE2 -exposed uteri, and incidence of ectopic glands and serous cysts were significantly increased in the prenatally EE2 -exposed ovaries as compared with respective controls. Significant upregulation of the aromatase mRNA was seen in the prenatally EE2 -exposed uteri and in the EE2 -exposed ovaries. The aromatase protein was identified in all ovaries examined, and in EE2 -exposed uteri but not in controls and confirmed its localization in eutopic and ectopic glands, abnormally proliferated lesions and the lining of the cysts. Taken together, continuous EE2 exposure may cause endometriotic and precancerous lesions due to excessive estrogen synthesis in both target organs.


Subject(s)
Endometriosis/chemically induced , Ethinyl Estradiol/pharmacology , Ovary/pathology , Precancerous Conditions/chemically induced , Sexual Maturation , Uterus/pathology , Animals , Blotting, Western , Ethinyl Estradiol/administration & dosage , Female , Mice , Mice, Inbred ICR , Real-Time Polymerase Chain Reaction
17.
Congenit Anom (Kyoto) ; 53(1): 18-26, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23480354

ABSTRACT

Before establishment of feto-placental circulation, decidua can synthesize hemoproteins to maintain oxygen homeostasis in situ. Using the human decidua of induced abortions ranging from 5 to 8 weeks of gestation, we determined the expression levels of erythropoietin, erythropoietin receptor, cytoglobin, myoglobin, embryonic-, fetal- and adult hemoglobin mRNA by quantitative RT-PCR analysis and identified their proteins by Western blot and immunohistochemical analyses. Erythropoietin signaling was demonstrated in phosphatidylinositol-3-kinase/protein kinase B pathway by Western blot, and the transcriptional factors for erythroid and non-erythroid heme synthesis were examined by RT-PCR analysis. In decidua, erythropoietin and its receptor mRNAs, erythropoietin receptor protein and phosphatidylinositol-3-kinase, were expressed with a peak at 6 weeks of gestation. Moreover, the decidua during 5 to 8 weeks of gestation expressed embryonic, fetal and adult hemoglobins additionally cytoglobin and myoglobin at transcriptional and protein levels. The heme portion of these hemoproteins is considered to be synthesized by non-erythroid δ-aminolevulinate synthase. These hemoproteins were discernible especially in decidual cells concomitant with cytotrophoblast cells and macrophage in these developing decidua. Considering the different capacity for oxygen binding and dissociation among hemoglobins with the oxygen storage capacity for cytoglobin and myoglobin, these hemoproteins appear to play a role in oxygen demand in decidua in situ before development of feto-placental circulation under the control of erythropoietin signaling.


Subject(s)
Decidua/metabolism , Erythropoietin/physiology , Hemeproteins/biosynthesis , Base Sequence , Blotting, Western , DNA Primers , Female , Humans , Immunohistochemistry , Polymerase Chain Reaction
18.
Tohoku J Exp Med ; 226(1): 55-8, 2012 01.
Article in English | MEDLINE | ID: mdl-22186037

ABSTRACT

Reversible posterior leukoencephalopathy syndrome (RPLS) is characterized by clinical symptoms such as seizures, visual disturbance, and altered mental status. It also presents abnormal findings on computed tomography (CT) and magnetic resonance imaging (MRI) indicating cerebral edema in the white matter of the occipital, temporal, and parietal lobes. Both the clinical symptoms and abnormal imaging findings can be reversed by controlling blood pressure or treating the underlying condition including infection. This report describes a patient with RPLS that occurred secondary to eclampsia. A 26-year-old female, gravida 0 para 0, developed weakness and pain in her upper and lower extremities and gait disturbance during the 34th week of pregnancy, and severe pregnancy-induced hypertension near the end of the 37th week. On the first day of the 38th week, she developed constricted visual fields and complained of visual illusions. MRI revealed a high-signal-intensity area in the right occipital lobe. Immediately after MRI, the patient had a 10-sec tonic convulsion. Diagnosed with eclampsia, she underwent emergency cesarean section. MRI on the 2nd postoperative day showed that the high-signal-intensity area was slightly improved. Her visual illusions were diminished by the 4th postoperative day, and almost all subjective symptoms disappeared by the 7th postoperative day. The patient was discharged at 12th postoperative day. We recommend MRI not only for symptomatic patients with suspected RPLS, but also for asymptomatic patients with severe pregnancy-induced hypertension. If findings such as cerebral edema are observed on MRI, immediate delivery should be considered before eclamptic seizures or exacerbation of neurological symptoms.


Subject(s)
Eclampsia/pathology , Hypertension, Pregnancy-Induced/pathology , Magnetic Resonance Imaging/methods , Posterior Leukoencephalopathy Syndrome/diagnosis , Posterior Leukoencephalopathy Syndrome/pathology , Adult , Cesarean Section , Female , Humans , Occipital Lobe/physiopathology , Posterior Leukoencephalopathy Syndrome/etiology , Pregnancy , Pregnancy Outcome , Treatment Outcome
19.
Tohoku J Exp Med ; 225(1): 1-3, 2011 09.
Article in English | MEDLINE | ID: mdl-21817850

ABSTRACT

Pulmonary thromboembolism (PE) is a serious postoperative complication. Reported rates of PE following gynecologic surgery are between 0.3% and 0.8%, with deep-vein thrombosis (DVT) as the major cause (via seeding of the lungs). Benign ovarian tumors are treated principally by surgery. Possible risk factors for DVT and PE in patients with benign ovarian tumors include tumor size, patient age, and obesity. To date, however, there has been no report addressing the association of these risk factors in patients with benign ovarian tumors. This study offers a retrospective analysis of the incident of preoperative DVT by age, tumor size, and BMI in patients undergoing surgery for benign ovarian tumors. A total of 843 Japanese patients with a preoperative diagnosis of benign ovarian tumor who underwent tumorectomy or adnexectomy at our institution between July 2003 and December 2010 were enrolled. The incidence of preoperative DVT was monitored and statistically stratified by age (< 50 years and ≥ 50 years), largest tumor diameter (< 10 cm and ≥ 10 cm), and BMI (< 25 and ≥ 25). The result indicates that tumor diameter of ≥ 10 cm is not a risk factor for preoperative DVT in patients with benign ovarian tumor. On the other hand, age ≥ 50 years and BMI > 25 are independent risk factors for preoperative DVT in Japan. The patients with each risk factor should be treated with preoperative, intraoperative, and postoperative precautions against development of PE.


Subject(s)
Ovarian Neoplasms/complications , Ovarian Neoplasms/epidemiology , Pulmonary Embolism/complications , Pulmonary Embolism/epidemiology , Venous Thrombosis/complications , Venous Thrombosis/epidemiology , Adult , Female , Humans , Japan/epidemiology , Risk Factors
20.
Tohoku J Exp Med ; 224(2): 87-9, 2011 06.
Article in English | MEDLINE | ID: mdl-21576892

ABSTRACT

Pulmonary thromboembolism (PE) may occur upon a patient's first postoperative attempt of ambulation. PE is a serious complication, often leading to shock or sudden death. Reported rates of PE following gynecologic surgery are between 0.3% and 0.8%, while the incidence of postoperative deep-vein thrombosis (DVT), the major cause of PE, is between 17% and 20%. Therefore, effective preventive measures, such as preoperative assessment for asymptomatic DVT, should be considered. It is well known that DVT and/or PE are associated with large uterine fibroids, the common, benign tumor of myometrium. Here, to establish the statistical relationship between DVT risk and uterine fibroid size/weight, we assessed the preoperative DVT rate with respect to three possible risk factors: age, obesity level, and uterine size/weight. A total of 361 patients with uterine fibroids undergoing hysterectomy between July, 2003 and December, 2009 were enrolled. All patients were evaluated for preoperative DVT; the results were stratified for statistical comparison by patient age, BMI, and uterine weight. There was no statistical difference in the DVT rate for patients stratified by age (below age 45 years or older) or BMI (below 25 or higher). By contrast, the rate of DVT was significantly higher for patients with uterine weights of 1,000 gm or more (11.5% [7/61]) compared with weights below 1,000 gm (3.0% [9/300]). None of the patients studied developed PE. In conclusion, the incidence of DVT is significantly higher in cases where uterine weight is 1,000 gm or more (ie, adult head size on pelvic examination).


Subject(s)
Leiomyoma/complications , Leiomyoma/pathology , Venous Thrombosis/etiology , Adult , Female , Humans , Middle Aged
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