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1.
J Clin Ultrasound ; 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38887803

RESUMO

We report a case of BPS combined with CPAM prenatally diagnosed as having two aberrant arteries from the celiac artery by fetal 3D-US. Although the pattern of arterial feeding vessels was extremely rare in our case, the vasculature images obtained using fetal 3D-US were comparable to those obtained using postnatal CT angiography.

2.
Mol Cell Biochem ; 478(2): 363-374, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35810415

RESUMO

Ascending inflammation from the vagina is a major cause of preterm birth. Currently, this condition-especially when uncontrolled-has no effective treatment. Human amniotic fluid stem cells (hAFSCs) are mesenchymal stem cells known to exert potent anti-inflammatory effects in animal models of perinatal diseases, such as periventricular leukomalacia, myelomeningocele, and neonatal sepsis. However, hAFSC therapy for inflammation-induced preterm birth has not been tested. In order to determine the therapeutic effect of hAFSC transplantation, we employed a preterm mouse model of ascending infection; this model was constructed by administering lipopolysaccharide to pregnant mice. We investigated the preterm birth rate and evaluated the inflammation of tissues, which is related to progressive infections, such as those involving the cervix, placenta, and lavage cells, using real-time qPCR. Further, we tracked the fluorescence of fluorescently labeled hAFSCs using an in vivo imaging system, and hAFSC aggregation was evaluated using immunohistochemistry analysis. We also investigated the presence of multiple types of peritoneal macrophages via flow cytometry analysis. Finally, we performed sphere culturing and co-culturing to determine the therapeutic effects of hAFSCs, such as their anti-inflammatory effects and their potential to alter macrophage polarization. We found that hAFSC administration to the peritoneal cavity significantly reduced inflammation-induced preterm birth in the mouse model. The treatment also significantly suppressed inflammation of the placenta and cervix. Transplanted hAFSCs may have aggregated with peritoneal macrophages, switching them from an inflammatory to an anti-inflammatory type. This property has been reported in vivo previously, but here, we examined the effect in vitro. Our findings support the hypothesis that hAFSCs suppress inflammation and reduce preterm birth by switching macrophage polarity. This study is the first to demonstrate that hAFSCs are effective in the treatment and prevention of inflammation-induced preterm birth.


Assuntos
Células-Tronco Mesenquimais , Nascimento Prematuro , Gravidez , Feminino , Humanos , Camundongos , Recém-Nascido , Animais , Líquido Amniótico , Nascimento Prematuro/prevenção & controle , Células-Tronco , Inflamação/induzido quimicamente
3.
J Epidemiol ; 33(9): 450-455, 2023 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-35370228

RESUMO

BACKGROUND: Progress in reducing the global low birthweight (LBW) has been insufficient. Although the focus has been on preventing preterm birth, evidence regarding LBW in term births is limited. Despite its low preterm birth prevalence, Japan has a higher LBW proportion than other developed countries. This study aimed to examine the prevalence of LBW in term singleton births and its associated factors using a national database. METHODS: We retrospectively analyzed the data of neonates registered in the Japan Society of Obstetrics and Gynecology Successive Pregnancy Birth Registry System who were born 2013-2017. Exclusion criteria included stillbirths, delivery after 42 gestational weeks, and missing data. Logistic regression analyses were performed to investigate the maternal and perinatal factors associated with LBW in term singletons using the data of 715,414 singleton neonates. RESULTS: The overall prevalence of LBW was 18.3%, and 35.7% of LBWs originated from singleton term pregnancies. Multiple logistic regression analyses indicated that both modifiable and non-modifiable factors were independently associated with LBW in term neonates. The modifiable maternal factors included pre-pregnancy underweight, inadequate gestational weight gain, and smoking during pregnancy, while the non-modifiable factors included younger maternal age, nulliparity, hypertensive disorders of pregnancy, cesarean section delivery, female offspring, and congenital anomalies. CONCLUSION: Using the Japanese pregnancy birth registry data, more than one-third of LBWs were found to originate from singleton term pregnancies. Both modifiable and non-modifiable factors were independently associated with LBW in term neonates. Prevention strategies on modifiable risk factor control will be effective in reducing LBW worldwide.


Assuntos
Nascimento Prematuro , Recém-Nascido , Feminino , Gravidez , Humanos , Peso ao Nascer , Nascimento Prematuro/epidemiologia , Estudos Retrospectivos , Japão/epidemiologia , Cesárea/efeitos adversos , Fatores de Risco , Sistema de Registros
4.
BMC Pregnancy Childbirth ; 23(1): 332, 2023 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-37161480

RESUMO

BACKGROUND: mRNA vaccination is an effective, safe, and widespread strategy for protecting pregnant women against infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, information on factors such as perinatal outcomes, safety, and coverage of mRNA vaccinations among pregnant women is limited in Japan. Therefore, this study aimed to investigate the perinatal outcomes, coverage, adverse effects, and short-term safety of mRNA vaccination as well as vaccine hesitancy among pregnant women. METHODS: We conducted a multicenter online survey of postpartum women who delivered their offspring at 15 institutions around Tokyo from October 2021 to March 2022. Postpartum women were divided into vaccinated and unvaccinated groups. Perinatal outcomes, COVID-19 prevalence, and disease severity were compared between the two groups. Adverse reactions in the vaccinated group and the reasons for being unvaccinated were also investigated retrospectively. RESULTS: A total of 1,051 eligible postpartum women were included. Of these, 834 (79.4%) had received an mRNA vaccine, while 217 (20.6%) had not, mainly due to concerns about the effect of vaccination on the fetus. Vaccination did not increase the incidence of adverse perinatal outcomes, including fetal morphological abnormalities. The vaccinated group demonstrated low COVID-19 morbidity and severity. In the vaccinated group, the preterm birth rate, cesarean section rate, and COVID-19 incidence were 7.2%, 33.2%, and 3.3%, respectively, compared with the 13.7%, 42.2%, and 7.8% in the unvaccinated group, respectively. Almost no serious adverse reactions were associated with vaccination. CONCLUSIONS: mRNA vaccines did not demonstrate any adverse effects pertaining to short-term perinatal outcomes and might have prevented SARS-CoV-2 infection or reduced COVID-19 severity. Concerns regarding the safety of the vaccine in relation to the fetus and the mother were the main reasons that prevented pregnant women from being vaccinated. To resolve concerns, it is necessary to conduct further research to confirm not only the short-term safety but also the long-term safety of mRNA vaccines.


Assuntos
COVID-19 , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Nascimento Prematuro , Recém-Nascido , Gravidez , Feminino , Humanos , Japão/epidemiologia , Gestantes , Cesárea , Estudos Retrospectivos , COVID-19/epidemiologia , COVID-19/prevenção & controle , SARS-CoV-2 , Nascimento Prematuro/epidemiologia , Vacinação/efeitos adversos , Inquéritos e Questionários
5.
Int J Clin Oncol ; 28(4): 587-591, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36662363

RESUMO

BACKGROUND: To investigate perinatal outcomes in pregnancy after high-dose medroxyprogesterone acetate (MPA) therapy for early stage endometrial cancer (EC) and atypical endometrial hyperplasia (AEH) and to determine whether pregnancy after MPA therapy is at a higher risk of placenta accreta. METHODS: Data of 51 pregnancies in 46 women who received MPA therapy for EC or AEH and delivered after 22 weeks of gestation at Keio University Hospital were reviewed. A retrospective matched case-control study was performed to determine the risk of placenta accreta in pregnancy after MPA therapy compared with singleton pregnancies without any history of maternal malignancy treatments. RESULTS: The incidence of placenta accreta was higher in the MPA group than in the control group (15.7 vs. 0%, p = 0.0058). However, no differences in other perinatal outcomes were observed between groups. While gestational weeks at delivery in the MPA group were later than those in the control group (p = 0.0058), no difference in the incidence of preterm delivery was recorded between groups. In the MPA therapy group, the number of patients who underwent ≥ 6 dilation and curettage (D&C) was higher in the placenta accreta group than in the non-placenta accreta group (50.0 vs. 14.0%, p = 0.018). Patients with ≥ 6 D&Cs demonstrated a 6.0-fold increased risk of placenta accreta (p = 0.043, 95% CI 1.05-34.1) than those receiving ≤ 3 D&Cs. CONCLUSION: Pregnancy after MPA therapy is associated with a high risk of placenta accreta. In cases in which the frequency of D&C is high, placenta accreta should be considered.


Assuntos
Hiperplasia Endometrial , Neoplasias do Endométrio , Hospitais , Acetato de Medroxiprogesterona , Estadiamento de Neoplasias , Placenta Acreta , Feminino , Humanos , Gravidez , Dilatação e Curetagem , Hiperplasia Endometrial/tratamento farmacológico , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/patologia , Acetato de Medroxiprogesterona/efeitos adversos , Acetato de Medroxiprogesterona/uso terapêutico , Placenta Acreta/induzido quimicamente , Placenta Acreta/etiologia , Nascimento Prematuro , Estudos Retrospectivos , Obstetrícia , Adulto , Pessoa de Meia-Idade
6.
Endocr J ; 70(5): 511-517, 2023 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-36792172

RESUMO

Hypoglycemia is one of the most significant problems in neonates born to mothers with gestational diabetes (GDM). This study aimed to identify novel predictors of hypoglycemia in neonates born to mothers with GDM. A total of 443 term singleton infants from mothers diagnosed with GDM and cared for at Keio University Hospital between January 2013 and December 2019 were included in this study. Neonatal hypoglycemia was defined as hypoglycemia of less than 47 mg/dL at 1 or 2 or 4 h after birth, according to previous studies. Among 443 full-term singleton neonates born to mothers with GDM, 200 developed hypoglycemia (45%). Gestational weight gain (GWG), HbA1c at 1st trimester, HbA1c at GDM diagnosis, and the incidence of insulin therapy in the neonatal hypoglycemia group were significantly higher than those in the non-neonatal hypoglycemia group (p = 0.016, p = 0.032, p = 0.011, and p = 0.017, respectively). Regarding the multiple regression analysis adjusted for nulliparity, GWG, and gestational weeks at delivery, the odds ratio for maternal HbA1c ≥5.2% at 1st trimester was 1.63 (p = 0.034), and maternal insulin therapy during pregnancy was 1.72 (p = 0.015). In conclusion, HbA1c in the 1st trimester and insulin therapy during pregnancy were good predictors of hypoglycemia in neonates born to GDM mothers, especially when their HbA1c was 5.2% or more. Further research will be necessary to improve the perinatal management of hypoglycemia.


Assuntos
Diabetes Gestacional , Doenças Fetais , Hipoglicemia , Doenças do Recém-Nascido , Insulinas , Gravidez , Recém-Nascido , Feminino , Humanos , Diabetes Gestacional/tratamento farmacológico , Diabetes Gestacional/epidemiologia , Diabetes Gestacional/diagnóstico , Hemoglobinas Glicadas , Fatores de Risco , Hipoglicemia/epidemiologia , Hipoglicemia/etiologia , Doenças do Recém-Nascido/epidemiologia , Doenças do Recém-Nascido/etiologia
7.
Int J Mol Sci ; 23(12)2022 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-35742877

RESUMO

Mesenchymal stem cells (MSCs) affect immune cells and exert anti-inflammatory effects. Human amniotic fluid stem cells (hAFSCs), a type of MSCs, have a high therapeutic effect in animal models of inflammation-related diseases. hAFSCs can be easily isolated and cultured from amniotic fluid, which is considered a medical waste. Hence, amniotic fluid can be a source of cells for MSC therapy of inflammatory diseases. However, the effect of hAFSCs on acquired immunity in vivo, especially on regulatory T cells, has not yet been fully elucidated. Therefore, in this study, we aimed to understand the effects of hAFSCs on acquired immunity, particularly on regulatory T cells. We showed that hAFSCs ameliorated the thioglycollate-induced inflammation by forming aggregates with host immune cells, such as macrophages, T cells, and B cells in the peritoneal cavity. Further, the regulatory T cells increased in the peritoneal cavity. These results indicated that, in addition to helping the innate immunity, hAFSCs could also aid the acquired immune system in vivo against inflammation-related diseases by increasing regulatory T cells.


Assuntos
Líquido Amniótico , Peritonite , Animais , Células Cultivadas , Humanos , Inflamação/terapia , Camundongos , Peritonite/induzido quimicamente , Peritonite/terapia , Células-Tronco , Tioglicolatos
8.
Gynecol Oncol ; 162(1): 220-225, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33902946

RESUMO

Radical trachelectomy (RT) is a surgery for early-stage cervical cancer treatment that preserves the childbearing ability, and its use has become increasingly common worldwide. Thus, the rate of conception in women who have undergone RT is increasing. However, pregnancy after RT is associated with a higher risk of several obstetric complications such as preterm delivery, preterm premature membrane rupture, and abnormal bleeding from varices at the site of uterovaginal anastomosis. Furthermore, since RT have a residual prophylactic cerclage, it is difficult to manage first- and second-trimester miscarriages. There is little previous data on the management of pregnancy after RT. In this review article, we summarize various management methods and experiences to provide a guide to clinicians for perinatal management after RT.


Assuntos
Gravidez , Traquelectomia , Feminino , Humanos , Resultado da Gravidez
9.
Acta Obstet Gynecol Scand ; 100(7): 1322-1325, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33797065

RESUMO

INTRODUCTION: Women who have undergone radical trachelectomy as a fertility-sparing treatment for early-stage cervical cancer may be at higher risk for retained tissues after early-term miscarriage due to cervical cerclage or cervical necrosis. Dilatation and curettage or aspiration may present additional risks in these women. The aim of this study was to assess the efficacy of expectant management for early pregnancy miscarriage after radical trachelectomy. MATERIAL AND METHODS: Keio University Hospital records were reviewed for women who conceived after abdominal radical trachelectomy and received perinatal care between 1 April 2012 and 31 March 2020. A total of 62 women (76 pregnancies) were identified, and 13 of these women experienced miscarriage before 12 gestational weeks. The management and outcome of these cases were reviewed in detail. RESULTS: The median maternal age at miscarriage was 39 years (range 31-42 years) and the median duration from abdominal radical trachelectomy to conception was 2.60 years (range 0.49-7.30 years). Cervical necrosis before conception occurred in one case (8%). One patient requested treatment with aspiration and the remaining 12 cases were managed with observation for a median of 23 days (range 7-50 days). There were no cases of endometritis or cases requiring dilatation and curettage for residue tissue. Further, no cases developed laceration of the residual cervix and no loss of cerclage sutures after discharge was noted. CONCLUSIONS: Expectant management seems to be safe and appropriate for first trimester miscarriage after abdominal radical trachelectomy.


Assuntos
Aborto Espontâneo/etiologia , Complicações Neoplásicas na Gravidez/cirurgia , Resultado da Gravidez/epidemiologia , Traquelectomia/efeitos adversos , Neoplasias do Colo do Útero/cirurgia , Conduta Expectante , Adulto , Feminino , Seguimentos , Humanos , Gravidez , Resultado do Tratamento
10.
Endocr J ; 68(11): 1321-1328, 2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34108310

RESUMO

Interventions for gestational diabetes mellitus (GDM), diagnosed in early pregnancy, have been a topic of controversy. This study aimed to elucidate factors that predict patients with GDM diagnosed before 24 gestational weeks (early GDM: E-GDM) who require insulin therapy later during pregnancy. Furthermore, we identified patients whose impaired glucose tolerance should be strictly controlled from early gestation onward. Women diagnosed with GDM were categorized based on the gestational age at diagnosis into E-GDM (n = 388) or late GDM (L-GDM, diagnosed after 24 weeks, n = 340) groups. Clinical features were compared between the groups, and the predictors for insulin therapy was evaluated in the E-GDM group. There were no significant between-group differences in terms of perinatal outcomes (e.g., gestational weeks at delivery, fetal growth, hypertensive disorder of pregnancy), with the exception of the Apgar score at 5 min. Moreover, there was no significant difference in the frequency of insulin therapy during pregnancy between the two groups. Using multiple logistic regression analysis, pre-pregnancy body mass index (BMI) ≥25 kg/m2, a family history of diabetes, and higher fasting plasma glucose (FPG), 1 h-plasma glucose (PG), and 2 h-PG values increased insulin therapy risk during pregnancy in the E-GDM group. Furthermore, since E-GDM patients with abnormal levels of FPG, as well as 1 h-PG or 2 h-PG, and those with pre-pregnancy BMI ≥25 kg/m2 and a family history of diabetes had a higher risk of later insulin therapy during pregnancy, they may require more careful follow-up in the perinatal period.


Assuntos
Glicemia , Índice de Massa Corporal , Diabetes Gestacional/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Adulto , Diabetes Gestacional/sangue , Diabetes Gestacional/diagnóstico , Feminino , Intolerância à Glucose , Teste de Tolerância a Glucose , Humanos , Insulina/sangue , Gravidez , Fatores de Risco
11.
Medicina (Kaunas) ; 57(9)2021 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-34577906

RESUMO

Background and objectives: Massive postpartum hemorrhage (PPH) is the most common cause of maternal death worldwide. A massive transfusion protocol (MTP) may be used to provide significant benefits in the management of PPH; however, only a limited number of hospitals use MTP protocol to manage massive obstetric hemorrhages, especially in Japan. This study aimed to assess the clinical outcomes in patients in whom MTP was activated in our hospital. Materials and Methods: We retrospectively reviewed the etiology of PPH, transfusion outcomes, and laboratory findings among the patients treated with MTP after delivery in our hospital. Results: MTP was applied in 24 cases (0.7% of deliveries). Among them, MTP was activated within 2 h of delivery in 15 patients (62.5%). The median estimated blood loss was 5017 mL. Additional procedures to control bleeding were performed in 19 cases, including transarterial embolization (18 cases, 75%) and hysterectomy (1 case, 4.2%). The mean number of units of red blood cells, fresh frozen plasma, and platelets were 17.9, 20.2, and 20.4 units, respectively. The correlation coefficients of any two items among red blood cells, fresh frozen plasma, platelets, blood loss, and obstetrical disseminated intravascular coagulation score ranged from 0.757 to 0.892, indicating high levels of correlation coefficients. Although prothrombin time and activated partial thromboplastin time levels were significantly higher in the <150 mg/dL fibrinogen group than in the ≥150 mg/dL fibrinogen group at the onset of PPH, the amount of blood loss and blood transfusion were comparable between the two groups. Conclusions: Our MTP provides early access to blood products for patients experiencing severe PPH and could contribute to improving maternal outcomes after resuscitation in our hospital. Our study suggests the implementation of a hospital-specific MTP protocol to improve the supply and utilization of blood products to physicians managing major obstetric hemorrhage.


Assuntos
Hemorragia Pós-Parto , Transfusão de Sangue , Feminino , Hospitais Universitários , Humanos , Japão , Hemorragia Pós-Parto/terapia , Gravidez , Estudos Retrospectivos
12.
Cardiol Young ; 30(6): 892-893, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32406365

RESUMO

The right aortic arch is a congenital vascular anomaly, which may form a vascular ring. However, prenatal identification of the branching pattern of brachiocephalic vessels is often limited. In this paper, we clearly demonstrated the branching pattern of brachiocephalic vessels in a case of right aortic arch with an aberrant left subclavian artery using HDlive Flow imaging.


Assuntos
Aorta Torácica/diagnóstico por imagem , Síndromes do Arco Aórtico/diagnóstico por imagem , Anormalidades Cardiovasculares/diagnóstico por imagem , Coração Fetal/anormalidades , Artéria Subclávia/anormalidades , Adulto , Aorta Torácica/anormalidades , Ecocardiografia Quadridimensional , Feminino , Coração Fetal/diagnóstico por imagem , Cardiopatias Congênitas/diagnóstico por imagem , Humanos , Imageamento Tridimensional , Gravidez , Diagnóstico Pré-Natal/métodos , Artéria Subclávia/diagnóstico por imagem , Ultrassonografia Pré-Natal , Anel Vascular/diagnóstico por imagem , Anel Vascular/patologia
13.
Int J Mol Sci ; 21(24)2020 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-33339379

RESUMO

A systemic inflammatory response induces multiple organ dysfunction and results in poor long-term neurological outcomes in neonatal sepsis. However, there is no effective therapy for treating or preventing neonatal sepsis besides antibiotics and supportive care. Therefore, a novel strategy to improve neonatal sepsis-related morbidity and mortality is desirable. Recently, we reported that prophylactic therapy with human amniotic stem cells (hAFSCs) improved survival in a rat model of lipopolysaccharide (LPS)-induced neonatal sepsis through immunomodulation. Besides improving the mortality, increasing survival without major morbidities is an important goal of neonatal intensive care for neonatal sepsis. This study investigated long-term neurological outcomes in neonatal sepsis survivors treated with hAFSCs using the LPS-induced neonatal sepsis model in rats. We found that prophylactic therapy with hAFSCs improved spatial awareness and memory-based behavior in neonatal sepsis survivors at adolescence in rats. The treatment suppressed acute reactive gliosis and subsequently reduced astrogliosis in the hippocampal region over a long period of assessment. To the best of our knowledge, this is the first report that proves the concept that hAFSC treatment improves cognitive impairment in neonatal sepsis survivors. We demonstrate the efficacy of hAFSC therapy in improving the mortality and morbidity associated with neonatal sepsis.


Assuntos
Disfunção Cognitiva/prevenção & controle , Gliose/prevenção & controle , Transplante de Células-Tronco Mesenquimais/métodos , Sepse Neonatal/complicações , Líquido Amniótico/citologia , Animais , Células Cultivadas , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/terapia , Gliose/etiologia , Gliose/terapia , Hipocampo/metabolismo , Hipocampo/patologia , Humanos , Masculino , Células-Tronco Mesenquimais/metabolismo , Ratos , Ratos Sprague-Dawley
14.
Pediatr Res ; 85(1): 97-104, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30120407

RESUMO

BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) remains a major cause of cerebral palsy. Increasing evidence has suggested that mesenchymal stem cells have a favorable effect on HIE. However, the efficacy of human amniotic fluid stem cells (hAFS) for HIE, especially in the chronic phase, remains unclear. The aim of this study was to determine the neurorestorative effect of hAFS on the chronic phase of HIE. METHODS: hAFS were isolated from AF cells as CD117-positive cells. HI was induced in 9-day-old mice. Animals intranasally received hAFS or phosphate-buffered saline at 10 days post HI and were harvested for histological analysis after functional tests at 21 days post HI. We also implanted PKH26-positive hAFS to assess their migration to the brain. Finally, we determined gene expressions of trophic factors in hAFS co-cultured with HI brain extract. RESULTS: hAFS improved sensorimotor deficits in HIE by gray and white matter restoration and neuroinflammation reduction followed by migration to the lesion. Brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), hepatocyte growth factor (HGF), and stromal cell-derived factor-1 (SDF-1) gene expressions in hAFS were elevated when exposed to HI-induced brain extract. CONCLUSION: hAFS induced functional recovery by exerting neurorestorative effects in HIE mice, suggesting that intranasal administration of hAFS could be a novel treatment for HIE, especially in the chronic phase.


Assuntos
Líquido Amniótico/citologia , Encéfalo/fisiopatologia , Hipóxia-Isquemia Encefálica/cirurgia , Células-Tronco Neurais/transplante , Neurogênese , Animais , Animais Recém-Nascidos , Comportamento Animal , Encéfalo/metabolismo , Encéfalo/patologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Movimento Celular , Células Cultivadas , Quimiocina CXCL12/metabolismo , Modelos Animais de Doenças , Fator de Crescimento de Hepatócito/metabolismo , Humanos , Hipóxia-Isquemia Encefálica/metabolismo , Hipóxia-Isquemia Encefálica/patologia , Hipóxia-Isquemia Encefálica/fisiopatologia , Masculino , Camundongos Endogâmicos C57BL , Atividade Motora , Fator de Crescimento Neural/metabolismo , Células-Tronco Neurais/metabolismo , Proteínas Proto-Oncogênicas c-kit/metabolismo , Transdução de Sinais
15.
Endocr J ; 66(7): 647-651, 2019 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-31019153

RESUMO

A number of data on gestational diabetes mellitus (GDM) in singleton pregnancy is available, however, little is known about the glycemic characteristics of twin pregnancy with GDM. The aim of this study was to compare the severity of dysglycemia between twin and singleton pregnancies with GDM (T-GDM and S-GDM). We retrospectively analyzed pregnancies with GDM defined by the Japan Diabetes Society criteria (T-GDM, n = 20; S-GDM, n = 451) in our hospital. During the study period, women with GDM underwent self-monitoring of blood glucose measurements as well as dietary management. Insulin treatment was initiated when dietary treatment did not achieve the glycemic goal. The glycemic and metabolic characteristics were compared between T-GDM and S-GDM, as follows: gestational week at the diagnosis of GDM, 75 g oral glucose tolerance test (OGTT) results, HbA1c, insulin secretion (i.e. insulinogenic index [IGI] and Insulin Secretion-Sensitivity Index-2 [ISSI-2]), and insulin requirement before delivery. The rate of one abnormal OGTT value in T-GDM was similar to that in S-GDM (60% vs. 71%). There were no significant differences in gestational week and levels of HbA1c at diagnosis, levels of IGI and ISSI-2 between T-GDM and S-GDM (median, 20 weeks vs. 17 weeks, 5.0% vs. 5.2%, 0.58 vs. 0.71, 1.7 vs. 1.8, respectively). The rate of insulin treatment and a median dosage of insulin needed before delivery was comparable between the two groups (T-GDM vs. S-GDM: 45% vs. 32% and 14 vs. 13 unit/day). Our data suggested that the severity of dysglycemia in T-GDM was similar to that in S-GDM during pregnancy.


Assuntos
Glicemia/metabolismo , Diabetes Gestacional/metabolismo , Resistência à Insulina/fisiologia , Gravidez de Gêmeos/metabolismo , Adulto , Estudos de Casos e Controles , Diabetes Gestacional/sangue , Feminino , Intolerância à Glucose/complicações , Intolerância à Glucose/metabolismo , Teste de Tolerância a Glucose , Humanos , Insulina/sangue , Células Secretoras de Insulina/metabolismo , Japão , Gravidez , Gravidez de Gêmeos/sangue , Estudos Retrospectivos
16.
Am J Med Genet A ; 176(1): 171-174, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29160033

RESUMO

Hypophosphatasia (HPP) is an autosomal recessive metabolic disorder with impaired bone mineralization due to mutations in the ALPL gene. The genotype-phenotype correlation of this disorder has been widely described. Here, we present two affected siblings, whose fetal phenotypes were discordant. A 31-year-old Japanese woman, G0P0, was referred to our institution because of fetal micromelia. After obstetric counseling, the pregnancy was terminated at 21 weeks' gestation. Post-mortem radiographs demonstrated severely defective mineralization of the skeleton. The calvarial, spinal, and tubular bones were mostly missing. Only the occipital bones, mandible, clavicles, ribs, one thoracic vertebra, ilia, and tibia were relatively well ossified. The radiological findings suggested lethal HPP. Genetic testing for genomic DNA extracted from the umbilical cord identified compound heterozygous mutations in the ALPL gene (c.532T>C, p.Y178H; c.1559delT, p.Leu520Argfs*86). c.532T>C was a novel variant showing no residual activity of the protein by the functional analysis. The parents were heterozygous carriers. In the next pregnancy, biometric values on fetal ultrasonography at 20 and 26 weeks' gestation were normal. At 34 weeks, however, a small chest and shortening of distal long bones came to attention. The neonate delivered at 41 weeks showed serum ALP of <5U/L. Radiological examination showed only mild thoracic hypoplasia and metaphyseal mineralization defects of the long bones. ALP replacement therapy was introduced shortly after birth, and the neonate was discharged at day 22 without respiratory distress. Awareness of discordant fetal phenotypes in siblings with HPP precludes a diagnostic error, and enables early medical intervention to mildly affected neonates.


Assuntos
Hipofosfatasia/diagnóstico , Fenótipo , Irmãos , Fosfatase Alcalina/genética , Alelos , Osso e Ossos/patologia , Genótipo , Idade Gestacional , Humanos , Hipofosfatasia/genética , Mutação , Diagnóstico Pré-Natal , Radiografia , Análise de Sequência de DNA
17.
Am J Med Genet A ; 176(1): i, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29232060

RESUMO

The cover image, by Satoru Ikenoue et al., is based on the Clinical Report Discordant fetal phenotype of hypophosphatasia in two siblings, DOI: 10.1002/ajmg.a.38531.


Assuntos
Radiografia , Humanos
18.
Endocr J ; 64(4): 463-475, 2017 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-28202837

RESUMO

Gestational diabetes (GDM) and type 2 diabetes (T2DM) share part of pathomechanism and several T2DM susceptibility genes are demonstrated to be associated with GDM. No information on the genetics of GDM, however, was available in Japanese women. In this study, T2DM risk variants (45 single nucleotide polymorphisms [SNPs] from 36 genes) identified in previous studies were genotyped using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry in a cohort of 171 Japanese women with GDM and 128 normal glucose tolerance (NGT) diagnosed by the new International Association of Diabetes in Pregnancy Study Group criteria. Of 45 SNPs, three genetic variants were nominally associated with the development of GDM: rs266729 (p = 0.013, odds ratio [OR]: 1.56, 95% confidence interval [CI]: 1.10-2.23) in ADIPOQ, rs10811661 (p = 0.035, OR: 1.46, 95% CI: 1.03-2.08) in CDKN2A/2B, and rs9505118 (p = 0.046, OR: 1.41, 95% CI: 1.01-1.97) in SSR1-RREB1. There was a significant difference in the number of risk alleles of three variants between women with GDM and NGT (3.79 ± 1.33 vs. 3.05 ± 1.41, p = 6.0 × 10-6). In combined analysis of three genetic variants, women with five or more risk alleles had a 7.32-fold increased risk of GDM (p = 5.6 × 10-5, 95% CI: 4.54-11.96), compared with those having no more than one risk allele. Our results suggest several risk variants of T2DM had cumulative effects on the development of GDM in Japanese women.


Assuntos
Diabetes Gestacional/genética , Polimorfismo de Nucleotídeo Único , Adulto , Povo Asiático/genética , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/etnologia , Diabetes Mellitus Tipo 2/genética , Diabetes Gestacional/etnologia , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Japão , Gravidez
19.
Int J Gynecol Cancer ; 26(1): 163-8, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26512787

RESUMO

OBJECTIVE: To investigate pregnancy outcomes in women after abdominal radical trachelectomy (RT) for early-stage cervical cancer. METHODS: The patients' background, fertility, and pregnancy outcomes were reviewed in a total of 61 pregnancies in 48 of 172 women who underwent abdominal RT at Keio University Hospital between September 2002 and December 2013. RESULTS: There were 5 women with stage IA1, 2 with stage IA2, and 41 with stage IB1. Histological types were as follows: squamous cell carcinoma (n = 36), adenocarcinoma (n = 10), and adenosquamous cell carcinoma (n = 2). The pregnancy rate of women attempting to conceive after abdominal RT was 44% (48/109). The mean ± SD duration from abdominal RT to conception was 3.1 ± 1.9 years. Of 61 pregnancies, 42 pregnancies were achieved by fertility treatment (in vitro fertilization-embryo transfer, 39; intrauterine insemination, 3). After excluding one pregnancy without detailed clinical information, there were 42 live births (5 in 22-27 weeks, 11 in 28-33weeks, 20 in 34-36 weeks, and 6 in 37-38 weeks), 13 miscarriages, and 5 ongoing pregnancies. While there were 10 first trimester miscarriages, 3 pregnancies ended in the second trimester owing to chorioamnionitis. The mean gestational age at birth was 33 weeks of pregnancy. Thirty-seven neonates were appropriate-for-date, and one was small-for-date. Six pregnancies exhibited massive bleeding from the residual cervix in the late pregnancy. Preterm birth less than 34 weeks of pregnancy was related to premature rupture of the membrane (P < 0.05). Chorioamnionitis was evident in 9 of 11 pregnancies with preterm premature rupture of the membrane followed by birth at less than 34 weeks of pregnancy. No parturients exhibited lochiometra and endometritis postpartum. CONCLUSIONS: Abdominal RT provided favorable pregnancy outcomes, and fertility treatment could be advantageous to conception. Massive bleeding from the residual cervix as well as ascending infection might be characteristic features during pregnancy after abdominal RT.


Assuntos
Abdome/cirurgia , Adenocarcinoma/cirurgia , Carcinoma Adenoescamoso/cirurgia , Carcinoma de Células Escamosas/cirurgia , Recidiva Local de Neoplasia/cirurgia , Traquelectomia , Neoplasias do Colo do Útero/cirurgia , Adenocarcinoma/patologia , Adulto , Carcinoma Adenoescamoso/patologia , Carcinoma de Células Escamosas/patologia , Feminino , Seguimentos , Humanos , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Gravidez , Resultado da Gravidez , Centros de Atenção Terciária , Fatores de Tempo , Neoplasias do Colo do Útero/patologia
20.
Endocr J ; 63(1): 101-4, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26510662

RESUMO

Though recommended for pregnant women at risk of preterm birth to improve perinatal outcomes, antenatal corticosteroid (ACS) treatment can cause maternal hyperglycemia, especially in cases of glucose intolerance. A standardized protocol for preventing hyperglycemia during ACS treatment remains to be established. We herein retrospectively investigated the time-dependent changes in insulin dose required for maternal glycemic control during ACS treatment in gestational diabetes (GDM). Twelve singleton pregnant women with GDM who received 12 mg of betamethasone intramuscularly twice 24 hours apart were included in this analysis. Of those, eight also received ritodrine hydrochloride for preterm labor. The blood glucose levels were maintained at 70-120 mg/dL with continuous intravenous infusion of insulin and nothing by mouth for 48 hours after the first betamethasone administration. After the first dose of betamethasone, the insulin dosage needed for glycemic control gradually increased and reached a maximum (6.6 ± 5.8 units/hr) at 10 hours, then, decreased to 4.1 ± 1.5 units/hr at 24 hours. Similar changes in the insulin requirement were found after the second betamethasone dose (the maximum insulin dosage: 5.5 ± 1.6 units/hr at 9 hours following the second administration). Women treated with ritodrine hydrochloride needed more insulin, than those without ritodrine hydrochloride treatment (130.8 ± 15.0 vs. 76.8 ± 15.2 units/day, respectively, p < 0.05). Our data indicated that the requirement for insulin is highest 9-10 hours after each dose of betamethasone. When GDM is treated with ACS, levels of blood glucose should be carefully monitored, especially in patients treated with ritodrine hydrochloride.


Assuntos
Corticosteroides/uso terapêutico , Glicemia/metabolismo , Diabetes Gestacional/tratamento farmacológico , Insulina/administração & dosagem , Nascimento Prematuro/prevenção & controle , Adulto , Glicemia/efeitos dos fármacos , Ritmo Circadiano/fisiologia , Diabetes Gestacional/sangue , Feminino , Humanos , Pessoa de Meia-Idade , Gravidez , Cuidado Pré-Natal/métodos , Estudos Retrospectivos , Fatores de Tempo
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