Acute aortic dissection (Stanford type B) during pregnancy.

We report a case of acute aortic dissection (Stanford type B) that occurred in pregnant woman at 34-week gestation. She had no systemic characteristics of Marfan syndrome, however she exhibited a mutation of FBN1, Arg 545 Cys, which has been found to correlate with ectopia lentis but not with aortic dissection.

Risk factors for maternal outcome in pregnancy complicated with dilated cardiomyopathy.

OBJECTIVE: The goal of the study was to determine risk factors for maternal cardiac failure in pregnancy complicated with dilated cardiomyopathy (DCM). STUDY DESIGN: The subjects were 29 patients diagnosed with DCM before conception or during the first 7 months of pregnancy. DCM was defined as left ventricle end-diastolic dimension (LVDd)≥48 mm and/or fractional shortening (%FS)≤30% on echocardiography. Patients were followed until at least 1 year after delivery and were categorized into a poor prognosis group (n=6; death or end stage heart failure of New York Heart Association (NYHA) class III and IV) and a good prognosis group (n=23; all other cases). RESULT: DCM was initially diagnosed during pregnancy in 6/6 and 8/23 patients in the poor and good prognosis groups, respectively (P<0.005). The %FS of the first test during pregnancy was 17.5±6.2 and 27.4±9.3% in the respective groups (P<0.005). In eight abortion cases with %FS 15.2±3.1%, %FS, cardiac function and NYHA class were maintained until 20 months after abortion. There was no relationship between LVDd and maternal outcome. CONCLUSION: Onset during pregnancy and decreased %FS are risk factors for a poor maternal outcome in patients with DCM. Abortion prevents further deterioration of cardiac function in patients with a very low %FS.

Causes of maternal mortality in Japan.

CONTEXT: Japan's maternal mortality rate is higher than that of other developed countries. OBJECTIVES: To identify causes of maternal mortality in Japan, examine attributes of treating facilities associated with maternal mortality, and assess the preventability of such deaths. DESIGN AND SETTING: Cross-sectional study of maternal deaths occurring in Japan between January 1, 1991, and December 31, 1992. SUBJECTS: Of 230 women who died while pregnant or within 42 days of being pregnant, 197 died in a hospital and had medical records available, 22 died outside of a medical facility, and 11 did not have records available. MAIN OUTCOME MEASURES: Maternal mortality rates per 100,000 live births by cause (identified by death certificate review and information from treating physicians or coroners); resources and staffing patterns of facilities where deaths occurred; and preventability of death, as determined by a 42-member panel of medical specialists. RESULTS: Overall maternal mortality was 9.5 per 100,000 births. Hemorrhage was the most common cause of death, occurring in 86 (39%) of 219 women. Seventy-two (37%) of 197 deaths occurring in facilities were deemed preventable and another 32 (16%) possibly preventable. Among deaths that occurred in a medical facility with an obstetrician on duty, the highest rate of preventable deaths (4.09/100,000 live births) occurred in facilities with 1 obstetrician. Among the 72 preventable deaths, 49 were attributed to 1 physician functioning as the obstetrician and anesthetist. While the unpreventable maternal death rate was highest in referral facilities, the preventable maternal death rate was 14 times lower in referral facilities than in transferring facilities. CONCLUSIONS: Inadequate obstetric services are associated with maternal mortality in Japan. Reducing single-obstetrician only delivery patterns and establishing regional 24-hour inpatient obstetrics facilities for high-risk cases may reduce maternal mortality in Japan. JAMA. 2000;283:2661-2667.

[Prenatal detection of the growth-retarded fetuses with a serious risk of adverse perinatal outcome by uterine artery Doppler flow velocimetry: a prospective study].

Our objective was to evaluate the predictive value of uterine artery Doppler flow velocimetry with regard to a serious risk of adverse perinatal outcome in growth-retarded fetuses. A prospective comparative study of pregnancies complicated with growth-retarded fetus with normal and abnormal uterine artery blood flow was performed. Ninety-three pregnancies were assessed by Doppler flow velocimetry in terms of the resistance index at 27-36 weeks. The relative risks (95% Confidence Interval) in 52 pregnancies with abnormal uterine artery blood flow compared with 41 pregnancies with normal uterine artery blood flow were as follows: Premature delivery: 2.29 (1.32-3.97), birth weight < 2,000g: 2.94 (1.74-4.97), cesarean section for fetal distress: 2.57 (1.30-5.05), admission to NICU: 3.27 (1.60-6.69). The findings in this study suggest that abnormal uterine artery blood flow is associated with a serious risk of adverse perinatal outcome in a pregnancy complicated with a growth-retarded fetus. Doppler flow velocimetry of the maternal uterine artery is useful for determining the clinical management of a pregnancy complicated with a growth-retarded fetus.

Soluble interleukin-6 (IL-6) receptor in the sera of pregnant women forms a complex with IL-6 and augments human chorionic gonadotropin production by normal human trophoblasts through binding to the IL-6 signal transducer.

To study the role of soluble interleukin-6 receptor (sIL-6R) during pregnancy, sIL-6R levels in the sera of pregnant women in the first, second, and third trimesters were determined and found to remain unchanged during pregnancy, but were significantly higher than those in nonpregnant women in the follicular, ovulatory, and luteal phases of the menstrual cycle (P < 0.001). IL-6 levels, however, in the sera of pregnant women at all trimesters showed no difference from those in nonpregnant women at any stage of the menstrual cycle. Recombinant sIL-6R (rsIL-6R) augmented hCG production by rIL-6-stimulated trophoblasts dose dependently, but failed to enhance hCG production by unstimulated trophoblasts. rIL-6- and rsIL-6R-induced hCG production was significantly blocked by anti-IL-6R antibody, PM1; antisignal transducing glycoprotein 130 (gp130) antibody, GPX7; or a tyrosine kinase inhibitor, genistein. Thus, sIL-6R in serum from pregnant women forms a complex with placental and decidual IL-6 in a manner similar to trophoblast membrane-bound IL-6R. These two discrete types of IL-6R and IL-6 complex might act cooperatively by binding to gp130 and subsequently evoking tyrosine kinase activity in the trophoblasts to produce hCG in vivo.

The interleukin-6 (IL-6)/IL-6-receptor system induces human chorionic gonadotropin production by activating tyrosine kinase-dependent signal transduction pathway different from pathways triggered by protein kinase activators including gonadotropin releasing hormone.

Interleukin-6 (IL-6) may play an important role in human CG (hCG) production by activating the IL-6-receptor (-R) system on human trophoblasts. Trophoblasts produced hCG in response to rIL-6 as well as to 8-bromo cAMP (8-Br-cAMP), 12-O-tetradecanoyl phorbol-13-acetate (TPA), and calcium ionophore A23187. To determine whether the signal transduction pathway activated by the IL-6-R system depends on protein kinases such as protein kinase A, protein kinase C, and Ca2+/calmodulin-dependent kinase, trophoblasts were stimulated with recombinant (r-) IL-6 in the presence or absence of protein kinase inhibitors such as N(2-methyl-aminoethyl)-5-isoquinoline sulfonamide dihydrochloride (H8), and 1-(5-isoquinolinesulfomyl)-2-methylpiperazine (H7) and a calmodulin antagonist, N-(6-aminohexyl)-5-chloro-1- napthalenesulfonamide (W7), H8, H7, and W7 failed to suppress rIL-6-induced hCG production but completely inhibited hCG production induced by 8-Br-cAMP, TPA, and the GnRH agonist (GnRHa), respectively. In contrast, genistein, a tyrosine kinase inhibitor, completely suppressed rIL-6-induced hCG production but failed to inhibit hCG production induced by 8-Br-cAMP, TPA, and A23187. Genistein also did not suppress GnRH-induced hCG production. The addition of genistein to rIL-1- and rTNF-alpha-stimulated trophoblasts inhibited rIL-1-induced and rTNF-alpha induced hCG production but maintained rIL-1- and rTNF-alpha-induced IL-6 production. These results show that the IL-6/IL-6-R system-induced signal transduction pathway in the placenta probably stimulates hCG production by activating a tyrosine kinase pathway. The experiment with genistein shows that the GnRH/GnRH-R system activates a signal transduction pathway distinct from that activated by the IL-6/IL-6-R system.

Placental interleukin-6 production is enhanced in intrauterine infection but not in labor.

OBJECTIVE: Because interleukin-6 is an important mediator in the host defense mechanism against infection and tissue damage, we studied the capacity of placentas with or without either labor or chorioamnionitis in the third trimester to produce interleukin-6. STUDY DESIGN: The placental blocks were cultured, and their interleukin-6 titers were measured by a bioassay. RESULTS: Placentas with labor produced a similar amount of interleukin-6 to placentas without labor. In contrast, placentas with chorioamnionitis produced much more interleukin-6 than the placentas with or without labor (p < 0.0001). CONCLUSION: Placental interleukin-6 is thus surmised to participate in potentiation of the placental and fetomaternal defense mechanisms together with placental interleukin-1 during chorioamnionitis.

Fetal mononuclear cells show a comparable capacity with maternal mononuclear cells to produce IL-8 in response to lipopolysaccharide in chorioamnionitis.

IL-8 is a chemotactic and activating cytokine for neutrophils which eliminate invading bacteria by releasing bactericidal metabolites. Cord blood mononuclear cells (CBMCs) obtained from neonates born to mothers with chorioamnionitis actively produced a significantly higher amount of IL-8 than those of neonates without chorioamnionitis, suggesting that the mononuclear cells of fetuses with chorioamnionitis had been activated in utero. As lipopolysaccharide (LPS) can often be detected in the uteroplacental space in chorioamnionitis, the LPS-mediated activation mechanism of neonatal mononuclear cells was analyzed in vitro to produce IL-8. Neonatal mononuclear cells stimulated with LPS increased IL-8 production in a time- and dose-dependent manner. The ability of term or preterm neonatal mononuclear cells to produce IL-8 was comparable with that of adult (maternal) mononuclear cells, suggesting functional maturity of the neonatal or fetal mononuclear cells to produce IL-8. However, IL-8 production by neonatal CBMCs was down-regulated by dexamethasone, a glucocorticoid which is clinically administered to mothers to promote fetal lung maturity in preterm delivery. Our present study revealed a regulatory mechanism of fetal IL-8 production, suggesting that functionally mature fetal mononuclear cells produce IL-8 in response to LPS in chorioamnionitis and activate the fetal defense mechanism against infection.

Human placenta constitutively produces interleukin-8 during pregnancy and enhances its production in intrauterine infection.

Interleukin-8 (IL-8) exerts unique chemotactic and activating activity on neutrophils. To address the significance of IL-8 in the fetoplacental unit during pregnancy, we cultured human placental explants that had been obtained by vaginal delivery, Caesarean section, or artificial abortion and then measured the IL-8 titer in the culture supernatants by enzyme immunoassay (EIA). Chorionic tissue from the first trimester produced a significant amount of IL-8 (2.2 +/- 0.4 ng/ml/10 mg, n = 5), while placentae in the second trimester (8.3 +/- 1.6 ng/ml/10 mg, n = 7) or at term (9.2 +/- 0.7 ng/ml/10 mg, n = 29) produced significantly higher amounts of IL-8. The presence or absence of labor did not affect the amount of placental IL-8 production. However, placentae with chorioamnionitis (25.2 +/- 1.6 ng/ml/10 mg, n = 9) showed significantly higher IL-8 production than those without chorioamnionitis (p less than 0.0001). Northern blot analysis of IL-8 mRNA expression demonstrated a constant level during pregnancy with or without chorioamnionitis, indicating the possibility that the major site of regulation of IL-8 synthesis in the placenta is posttranscriptional. Immunohistochemical analysis of first and third trimester placental tissues with rabbit anti-IL-8 antibody revealed the IL-8 producing cells to be trophoblasts and macrophage-like cells. IL-8 produced by the placental cells might contribute to potentiation of the immunocompetence of placental cells against bacteria invading the fetoplacental unit.

The use of serum TA-4 in monitoring patients with malignant transformation of ovarian mature cystic teratoma.

The development of cancer in mature cystic teratomas of the ovary is rare and sometimes difficult to detect because of sampling errors. Six cases of squamous cell carcinoma arising in ovarian mature cystic teratomas were studied, five of which showed an elevated level of a squamous cell carcinoma-associated antigen, TA-4, in the sera obtained preoperatively; the preoperative determination was not performed in the sixth case. However, no elevated TA-4 level was detected in the sera of 28 patients with mature cystic teratomas of the ovary. Moreover, serial determination of the serum TA-4 level showed a good correlation between the clinical course and the serum TA-4 level. Interestingly, an abnormal TA-4 level preceded the clinical detection of recurrence by 2 months in two patients. Thus, determination of the serum TA-4 concentration may be useful for diagnosing and monitoring patients with squamous cell carcinoma arising in mature cystic teratomas of the ovary.