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C J Lockwood

Publications and source records attributed to C J Lockwood.

At least 55 records · Page 3Linked to original sources
PubMed1999

Markers of risk for preterm delivery.

Clinical and experimental evidence indicate that PTD results from four primary pathogenic mechanisms: activation of the maternal or fetal HPA axis; amniochorionic-decidual or systemic inflammation; decidual hemorrhage; and, pathologic distention of the myometrium. Each of these four pathways has a distinct epidemiological and clinical profile, and unique biochemical and biophysical pathways initiating parturition, but shares a common final biochemical pathway involving myometrial activation and stimulation, and enhanced genital tract protease activity promoting PPROM and cervical change. Traditional methods of predicting women at risk relying on obstetrical history or symptoms and epidemiological risk factors are neither sensitive nor specific. Recent approaches to predicting PTD, including sonographic measurement of cervical length and biochemical assays for hCG, cytokines, fFN, MMPs, estrogens, and CRH, are more sensitive than traditional methods. Moreover, given the heterogeneous, interactive etiopathogeneses of PTD, multiple biochemical markers should not only increase sensitivity and specificity, but also permit the detection of the relative contribution of each pathogenesis to the overall risk of PTD.

Biomarkers↗
PubMed1999

Measurement of the amniotic fluid index with and without color Doppler.

AIMS: The purpose of this study was to assess the effect, if any, of color Doppler on the measurement of the amniotic fluid index in term pregnancies. It is hypothesized that color Doppler may enhance the detection of oligohydramnios. METHODS: The amniotic fluid index was performed with and without color Doppler on pregnancies greater than or equal to 36 weeks gestational age. Differences in the mean amniotic fluid index measurements were assessed. The incidence of oligohydramnios was examined using both techniques. Differences in continuous variables were assessed with the paired t test, differences in categorical variables were assessed using the Fisher Exact Test. RESULTS: There were 155 pregnancies examined, the amniotic fluid index was significantly decreased when color Doppler was added to the standard technique. (P < .0001) The incidence of oligohydramnios was higher with the application of color Doppler to the standard amniotic fluid index. (P < .05). CONCLUSIONS: Color Doppler results in a significantly lower amniotic fluid volume measurement and may enhance the detection of oligohydramnios.

Adult↗
PubMed1998

Cervical fetal fibronectin correlates to prostaglandin E2-induced cervical ripening and can be identified in cervical tissue.

OBJECTIVE: Our purpose was to investigate whether prostaglandin E2-induced cervical ripening can be related to changes in fetal fibronectin levels and whether fetal fibronectin can be detected by immunohistochemistry in amniotic and cervical tissue. STUDY DESIGN: Fetal fibronectin levels in cervical mucus were quantitated in 28 nulliparous term pregnant women with unfavorable cervical states before and after intracervical application of prostaglandin E2 gel. The concentration of fetal fibronectin was determined with use of an enzyme immunoassay. Cervical biopsy specimens and amniotic tissue for immunohistochemical analysis were obtained from three term pregnant women and after parturition in three women. Cervical biopsy specimens from two nonpregnant women served as controls. Immunohistochemical analysis was performed with antibodies directed toward fetal fibronectin. RESULTS: The fetal fibronectin level in cervical mucus was low in all women before prostaglandin E2 application. In women with a successful prostaglandin E2-induced ripening (i.e., an increase of cervical score with > or =3 points), a tenfold increase in the fetal fibronectin level was registered. In women with an insufficient cervical ripening after prostaglandin E2 treatment no significant increase in the fetal fibronectin level was registered. The immunohistochemical analyses have identified fetal fibronectin in the epithelial cells of the cervix uteri. CONCLUSION: Successful prostaglandin E2-induced cervical ripening seems to be related to a significant increase in cervical fetal fibronectin levels. Fetal fibronectin can be detected immunohistochemically in the pregnant human cervix.

Adult↗
PubMed1998

Pregnancy outcome and weight gain recommendations for the morbidly obese woman.

OBJECTIVE: To compare pregnancy outcomes between morbidly obese and nonobese women and to determine the effect of gestational weight gain on pregnancy outcome in morbidly obese women. METHODS: A retrospective cohort study was conducted comparing 613 morbidly obese and 11,313 nonobese women who were delivered of a singleton live birth. Morbid obesity was defined as a body mass index greater than 35. The incidence of selected perinatal and neonatal outcomes was assessed for the two groups. Multiple logistic regression analysis was used to evaluate the association between morbid obesity and various measures of outcome while controlling for potential confounders. A subanalysis of the morbidly obese patients was performed to assess the effect of gestational weight gain on pregnancy outcome. RESULTS: Morbidly obese patients were more likely to experience pregnancy complications including diabetes, hypertension, preeclampsia, and arrest-of-labor disorders; however, these were not affected by gestational weight gain. Morbidly obese patients were more likely to experience fetal distress and meconium and to undergo cesarean delivery than their nonobese counterparts (P < .05). Weight gains of more than 25 lb were associated strongly with birth of a large for gestational age (LGA) neonate (P < .01); however, poor weight gain did not appear to increase the risk of delivery of a low birth weight neonate. CONCLUSION: Gestational weight gain was not associated with adverse perinatal outcome, but it did influence neonatal outcome. To reduce the risk of delivery of an LGA newborn, the optimal gestational weight gain for morbidly obese women should not exceed 25 lb.

Adult↗
PubMed1998

The effect of fetal intravascular blood transfusion on plasma endothelin levels in fetuses with rhesus alloimmunization.

OBJECTIVE: To determine if intrauterine intravascular fetal transfusion affects fetal umbilical venous endothelin levels. METHODS: Endothelin concentrations were measured by radioimmunoassay in fetal umbilical venous blood obtained immediately before and after 36 fetal transfusions performed for Rh alloimmune hemolytic anemia. Umbilical venous pressures also were recorded before and after transfusion. RESULTS: The mean (+/- standard deviation [SD]) gestational age at transfusion was 27.0 +/- 4.6 weeks, whereas the initial and post-transfusion hematocrits were 23.3 +/- 8.5% and 41.8 +/- 6.3%, respectively. Post-transfusion endothelin levels correlated significantly with the volume of transfused blood (r = .41; P = .03) and with post-transfusion increases in umbilical vein pressure (r = .86; P < .001). Among fetuses undergoing initial transfusion, there were significant differences between mean (+/- SD) pre- and post-transfusion endothelin levels [3.6 (+/- 2.2) pg/mL versus 6.3 (+/- 4.0) pg/mL, respectively; P = .02]. In contrast, among fetuses undergoing a repeat fetal transfusion, no differences in mean (+/- SD) pre- versus post-transfusion endothelin levels were observed [3.8 (+/- 1.8) pg/mL versus 2.2 (+/- 1.77) pg/mL, respectively; P = .3)]. Step-wise multiple regression analysis identified order of transfusion as a significant predictor of change in endothelin levels from pre- to post-transfusion measurements (adjusted r2 = .26; P = .003). CONCLUSION: Rapid expansion of fetal intravascular volume by intravenous transfusion of packed red blood cells with a high hematocrit enhances fetal endothelin levels in those fetuses undergoing initial but not subsequent transfusions.

Adult↗
PubMed1998

Matrix metalloproteinase and matrix metalloproteinase inhibitor expression in endometrial stromal cells during progestin-initiated decidualization and menstruation-related progestin withdrawal.

Estradiol (E) primes human endometrial stromal cells (HESCs) for the decidualizing effects of progesterone in vivo and in vitro. Matrix metalloproteinase (MMP) expression was evaluated in confluent HESCs incubated in control medium, and in medium supplemented with either E, or the synthetic progestin medroxyprogesterone acetate (P), or E + P. Measurements with a specific ELISA indicated that basal pro-MMP-1 output was unaffected by E, whereas E + P, which induces the expression of several decidualization-related markers, produced a time-dependent inhibition in HESC-secreted levels of pro-MMP-1. Consistent with progestin inhibition of MMP-1 protein expression in the HESCs, P but not E, reduced steady state levels of MMP-1 messenger RNA (mRNA) as determined by Northern analysis. By contrast, mRNA levels for MMP-2 and the MMP inhibitor TIMP-1 were not altered by either P or E. Steroid withdrawal studies indicated that after MMP-1 expression was suppressed by incubation of the HESCs with E + P, 4 days of exposure to the antiprogestin RU 486 (mifepristone) significantly up-regulated MMP-1 levels in the conditioned medium by severalfold compared with cultures maintained in E + P. The change to steroid-free control medium required a more prolonged period of withdrawal to attain up regulatory effects that were comparable with those evoked by RU 486. The ELISA measurements were validated by immunoblot analysis with a specific MMP-1 antibody, which showed corresponding changes in a band at the expected mobility of about 50 kDa. Moreover, Northern analysis revealed parallel changes in MMP-1 mRNA levels, whereas neither MMP-2 nor TIMP-1 mRNA levels were modulated by adding or withdrawing steroids. The contrast between regulated MMP-1 expression and constitutive MMP-2 expression observed in the cultured HESCs is consistent with the demonstrated presence on the MMP-1 promoter of regulatory elements such as AP-1 and PEA-3 that are absent from the MMP-2 promoter. Extrapolation of these in vitro changes in HESCs to in vivo endometrial events suggests that: 1) inhibition of MMP-1 expression by E and progesterone would stabilize the perivascular endometrial ECM to prevent local hemorrhage during endovascular invasion by the implanting trophoblast; 2) enhanced expression of MMP-1 evoked by steroid withdrawal would mediate endometrial ECM degradation leading to sloughing of the functional layer during menstruation.

Blotting, Northern↗
PubMed1998

Chronic antagonism of nuclear factor-kappaB activity in cytotrophoblasts by dexamethasone: a potential mechanism for antiinflammatory action of glucocorticoids in human placenta.

Circulating glucocorticoids are present in increasing quantities as human gestation progresses, peaking during labor whether it occurs before or at term. Although the precise role of glucocorticoids in pregnancy is not well defined, it is clear that glucocorticoids suppress inflammation in many cell types by antagonizing the acute stimulatory actions of members of the Rel/nuclear factor-kappaB (NF-kappaB) family on cytokine gene expression. In the present study we tested the hypothesis that during pregnancy, glucocorticoids chronically suppress inflammation in the human placenta. Cytotrophoblasts obtained from human term placentas were maintained for 48 h in culture medium supplemented with 10% charcoal-stripped calf serum with and without 100 nmol/L dexamethasone (DEX). Enzyme-linked immunosorbent assay studies revealed that cytotrophoblasts constitutively express interleukin-8 (IL-8), a known mediator of placental inflammation, between 24-96 h of culture. A 48-h treatment of cytotrophoblasts with 100 nmol/L DEX significantly reduced the production of IL-8 to 24+/-1% of control levels (P < 0.01). DEX and cortisol mediated a dose-dependent inhibition of IL-8 expression, with ED50 values of 5 and 50 nmol/L, respectively. DEX treatment also significantly reduced levels of IL-6 and tumor necrosis factor-alpha in culture medium, suggesting that glucocorticoids coordinately reduce cytokine levels in cytotrophoblasts. As cytokine expression is regulated by NF-kappaB and activator protein-1 (AP-1) transcription factors, electrophoretic mobility shift assays (n = 4) were used to determine whether DEX treatment altered the binding of nuclear proteins from cytotrophoblasts to labeled oligonucleotides corresponding to the kappaB and AP-1 response elements. We observed that a 48-h treatment of cytotrophoblasts with 100 nmol/L DEX markedly reduced binding of nuclear extracts from cytotrophoblasts to the kappaB response element. DEX treatment promoted a relatively smaller reduction of binding to the AP-1 response element. Northern blotting experiments revealed that DEX treatment did not alter the level of IkappaB, p50, or p65 messenger ribonucleic acid, suggesting that the antiinflammatory action of glucocorticoid in cytotrophoblasts did not directly involve alterations in the level of NF-kappaB proteins. Our results demonstrate a novel chronic suppressive action of glucocorticoid on cytokine production and nuclear binding of NF-kappaB and AP-1 proteins in cytotrophoblasts, providing a potential mechanism through which glucocorticoids may suppress inflammation at maternal-fetal interfaces across gestation.

Anti-Inflammatory Agents↗
PubMed1998

Glucocorticoid effects in the human placenta: evidence that dexamethasone-mediated inhibition of fibronectin expression in cytotrophoblasts involves a protein intermediate.

Oncofetal fibronectin is an extracellular matrix protein that is suggested to play an important role in regulating adherence at uterine-placental interfaces. The purpose of the present study was to elucidate a mechanism through which glucocorticoids (GCs) inhibit the synthesis of FN in human placenta as part of their matrix-suppressive action near parturition. We observed that treatment of cytotrophoblasts isolated from human term placentas for 48 h with 10(-7) mol/L dexamethasone (DEX) down-regulated levels of FN expression to 13-19% of control levels in immunoprecipitation, Northern blotting, and enzyme-linked immunosorbent assay experiments. Conversely, GC treatment increased FN expression in placental fibroblasts to 164-310% of control levels in Northern blotting and enzyme-linked immunosorbent assay procedures, suggesting that GC-mediated suppression of FN expression is specific to cytotrophoblasts. Results indicated that the DEX-mediated suppression of FN expression in cytotrophoblasts was not mediated through changes in the stability of FN messenger ribonucleic acid (mRNA). Run-on transcription assays using isolated nuclei suggested that GC treatment did not markedly affect transcription of the FN gene in cytotrophoblasts. To test whether the GC-mediated suppression of FN expression was mediated through a protein intermediate, levels of FN mRNA were examined by Northern blotting in cells treated for 48 h with and without 10(-7) mol/L DEX and cycloheximide (CHX; 125 ng/mL). We observed that CHX treatment increased FN expression in DEX-treated cells to 91% of control values. We noted that whereas the presence of 100-300 ng/mL CHX reversed the DEX-mediated inhibition of FN mRNA expression in cytotrophoblasts, it did not alter the overall rates of protein synthesis in DEX-treated and control cells. These data suggest that suppression of FN mRNA expression by GC in cytotrophoblasts requires de novo protein synthesis and is mediated through a short lived intermediate, the synthesis of which is inhibited at low concentrations of CHX. Thus, GC-induced protein intermediates may influence uterine-placental adherence by modulating levels of oncofetal FN at sites of uterine-placental contact.

Blotting, Northern↗
PubMed1998

Apoptosis and Fas expression in human fetal membranes.

Apoptosis (i.e. programmed cell death) plays a key role in maintaining reproductive function in the ovary, mammary and prostate glands, uterus, and testis. The purpose of the present report was to determine, based on biochemical and morphological parameters, whether cells in human fetal membranes undergo apoptosis and express Fas (CD95), a cell surface receptor that mediates apoptosis. Using the terminal deoxynucleotidyl transferase deoxy-UTP-nick end labeling immunohistochemical technique, apoptotic nuclei were identified in amnion epithelial, chorionic trophoblast, and decidua parietalis cell layers of human fetal membranes at term. Electron microscopy of fetal membranes revealed ultrastructural characteristics in amnion epithelium and chorion trophoblast cell layers consistent with apoptosis, including condensation of chromatin along the periphery of the nucleus and nuclear shrinkage. The apoptotic index (percentage of terminal deoxynucleotidyl transferase deoxy-UTP-nick end labeling-positive nuclei of the total nuclei) ranged from 8-29% in amnion epithelial, chorionic trophoblast, and decidual cell layers from women at 23-30, 31-36, and 37-42 weeks gestation. The apoptotic index was statistically greater in the 37-42 week group than in the 23-30 week group in chorionic trophoblast (P < 0.05) and decidual cell (P < 0.01) layers. In contrast, the apoptotic index in the amnion epithelial cell layer was statistically greater (P < 0.05) in the 23-30 week group than in the 31-36 week group, suggesting that apoptosis may be independently regulated in amnion epithelial, chorionic trophoblast, and decidual cell types. Based on the importance of Fas in mediating apoptosis, we investigated whether Fas was expressed by human fetal membrane cells. Immunohistochemical staining of fetal membranes with anti-Fas antibody localized Fas in amnion epithelial, chorionic trophoblast, and decidua parietalis cell layers. A 266-bp band corresponding to the cytoplasmic domain of Fas was detected in samples of amnion, chorion, decidua, and placenta by RT-PCR. Northern blotting revealed a molecular weight of approximately 1.9 kilobases for Fas messenger ribonucleic acid in amniotic tissue. These data suggest that apoptosis and Fas signaling may play a role in remodeling of fetal membrane architecture across gestation.

Amnion↗
PubMed1998

Transcriptional regulation of the tissue factor gene by progestins in human endometrial stromal cells.

Decidualization of estradiol (E2)-primed human endometrial cells (HESCs) by progesterone is associated with elevated levels of tissue factor (TF), the primary initiator of hemostasis. Similarly, in cultured human HESCs, the synthetic progestin, medroxyprogesterone acetate (MPA), enhances TF protein and messenger ribonucleic acid (mRNA) levels. Although ineffective alone, E2 potentiates this progestin enhancement of TF expression by HESCs. The current study examines mechanisms underlying MPA enhancement of TF mRNA expression in HESCs. In the presence of the transcription-blocking agent dichlororibofuranosylbenzimidazole, no significant differences were noted in the half-lives of TF mRNA isolated from HESCs treated with E2 alone or with E2 plus MPA. This indicates that MPA-enhanced TF mRNA levels do not reflect changes in the stability of the TF message. To test the effect of progestin on TF promoter activity and to ascertain the mechanism of promoter regulation, primary or first passaged HESCs were transfected with TF promoter constructs spanning the regions -2106 to +121 (TFp(-2106)), -278 to +121 (TFp(-278)), and -111 to +14 (TFp(-111)) bp upstream of the transcription start site. MPA was found to enhance TF transcription by 20-fold in HESCs transfected with TFp(-2106) after correcting for transfection efficiencies with a beta-galactosidase reporter plasmid. Interestingly, levels of E2- plus MPA-stimulated transcription were significantly increased using TFp(-278) compared to TFp(-2106), suggesting that the region between -2106 and -278 bp may contain an inhibitory element. In addition, rates of MPA-stimulated transcription using TFp(-111) were significantly reduced compared to values obtained using TFp(-2106) and were even further reduced compared to values obtained using TFp(-278). This suggests that regulatory elements in the -111 bp region of the TF promoter are necessary for progestin-mediated regulation of the TF gene in HESCs, but are not sufficient to account for maximal rates of TF gene transcription. Our results also demonstrated that induction of steady state TF mRNA by MPA was abolished by treating cells with E2 plus MPA in conjunction with the protein synthesis inhibitor cycloheximide. In light of the absence of a complete progesterone or estrogen response element in the published 5'-sequence of the TF promoter, our results suggest that progestin-enhanced transcription of TF mRNA in stromal cells may be mediated by an uncharacterized protein intermediate(s).

Cells, Cultured↗
PubMed1997

Decidual cell regulation of hemostasis during implantation and menstruation.

Progesterone stimulation of the estradiol (E2)-primed human endometrium initiates DZ of the stromal cells around the spiral arterioles. Under continued steroid stimulation, DZ spreads wave-like to establish the decidual cell as a major cell type of the luteal phase and pregnant endometrium. Because of their widespread distribution throughout the endometrium and concentration at perivascular sites, decidual cells are spatially and temporally positioned to mediate the opposing requirements of maintaining hemostasis during endovascular trophoblast invasion, yet promoting menstrual hemorrhage in the absence of implantation. The experimental results summarized in this review indicate that the paradoxical properties manifested by endometrial stromal/decidual cells are controlled by several proteins with either hemostatic or ECM-degrading or vasoactive activity, and that their expression is altered in response to changes in levels of circulating ovarian steroids during the menstrual cycle. These conclusions are drawn primarily from studies with a well-characterized in vitro model of DZ using monolayers of stromal cells derived from specimens of predecidualized endometrium. Thus, progestins modify the expression of several DZ-related markers in the cultured stromal cells, and E2 enhances these effects despite the lack of response to E2 alone. These responses are consistent with the differential actions displayed by E2 and progesterone in vivo, by which E2 primes the endometrium for the decidualizing effects of progesterone by elevating progesterone receptor levels. Accordingly, during steroid-induced in vitro DZ, a marked increase in the expression of stromal cell TF and PAI-1 and reciprocal inhibition of tPA activity suggest mechanisms to account for the absence of hemorrhage during invasion of the endometrial vasculature by implanting trophoblasts. In contrast to steroid-induced DZ, the events of menstruation are initiated in response to a decline in circulating levels of ovarian steroids. Accordingly, subjecting in vitro decidualized stromal cells to steroid withdrawal results in pronounced reversal in the expression of all of the end points listed above. Consequently, the local hemostatic environment is transformed into a hemorrhage-promoting milieu. Taken together with vascular injury resulting from ischemia induced by spiral artery vasoconstriction, the net effect is attainment of two prerequisites for menstrual hemorrhage, vascular injury and inadequate hemostasis.

Decidua↗
PubMed1997

Pregnancy loss in the antiphospholipid-antibody syndrome--a possible thrombogenic mechanism.

BACKGROUND: The mechanisms of vascular thrombosis and pregnancy loss in the antiphospholipid-antibody syndrome are unknown. Levels of annexin V, a phospholipid-binding protein with potent anticoagulant activity, are markedly reduced on placental villi from women with this syndrome. Hypercoagulability in such women may therefore be due to the reduction of surface-bound annexin V by antiphospholipid antibodies. To test this idea, we studied how antiphospholipid antibodies affect levels of annexin V on cultured trophoblasts and human umbilical-vein endothelial cells and how they affect the procoagulant activity of these cells. METHODS: We isolated IgG fractions from three patients with the antiphospholipid-antibody syndrome and from normal controls. These antibodies were incubated with cultured BeWo cells (a placental-trophoblast cell line), primary cultured trophoblasts, and human umbilical-vein endothelial cells. Annexin V on the cell surfaces was measured by an enzyme-linked immunosorbent assay. The coagulation times of plasma overlaid on the cells were also determined. RESULTS: Trophoblasts and endothelial cells exposed to antiphospholipid-antibody IgG as compared with control IgG had reduced levels of annexin V (trophoblasts, 0.37 +/- 0.02 vs. 0.85 +/- 0.12 ng per well, P=0.02; endothelial cells, 1.6 +/- 0.04 vs. 2.1 +/- 0.05 ng per well, P=0.001). Also, trophoblasts and endothelial cells exposed to antiphospholipid-antibody IgG had faster mean (+/- SE) plasma coagulation times than cells exposed to control IgG (trophoblasts, 8.7 +/- 2.0 vs. 21.3 +/- 2.9 minutes, P=0.02; endothelial cells, 9.8 +/- 0.8 vs. 14.2 +/- 1.2 minutes, P=0.04). CONCLUSIONS: Antiphospholipid antibodies reduce the levels of annexin V and accelerate the coagulation of plasma on cultured trophoblasts and endothelial cells. The reduction of annexin V levels on vascular cells may be an important mechanism of thrombosis and pregnancy loss in the antiphospholipid-antibody syndrome.

Abortion, Spontaneous↗
PubMed1997

Prothrombin activation fragment (F1.2) is increased in pregnant patients with antiphospholipid antibodies.

Recurrent fetal wastage has been attributed to thrombosis in the antiphospholipid antibody syndrome (APAS); however, this has not been proven. Assays of coagulation activation fragments which may provide evidence for a role for thrombosis, have not been previously reported in this setting. We therefore investigated whether F1.2 levels are altered in APAS pregnancies. F1.2 levels were performed on plasmas obtained from fifty-four APA patients with a history of persistent elevation of antiphospholipid antibodies and recurrent abortion who were studied during eighty-three consecutive visits. Results from these patients were compared to a control group of thirty-two healthy pregnant females. F1.2 levels were significantly higher in APAS patients than controls in the second trimester (6.5 nM +/- 4.3 nM vs. 1.2 nM +/- 0.9 nM, p < 0.0001), and in the third trimester of pregnancy (8.6 nM +/- 2.5 nM vs. 3.7 nM +/- 2.0 nM, p < 0.0001). The F1.2 levels in the APA group returned to baseline soon after delivery. No correlation was observed between F1.2 and APA values. This study shows that pregnant patients with a history of recurrent abortions and APA have significantly increased activation of prothrombin compared to healthy pregnant females. These data indicate that the potential value of activations peptide assays such as F1.2 in this setting should be tested in prospective clinical trials.

Adult↗
PubMed1997

Antiphospholipid immunoglobulin G antibodies reduce annexin-V levels on syncytiotrophoblast apical membranes and in culture media of placental villi.

OBJECTIVES: The mechanism by which antiphospholipid antibodies are associated with pregnancy loss and thromboembolism has not been established. We previously showed that annexin-V, a phospholipid-binding protein with potent anticoagulant activity, is present on the apical membranes of the syncytiotrophoblasts that line placental villi and that this protein is reduced, by immunohistochemistry, on placentas of patients with antiphospholipid antibodies. We therefore investigated whether annexin-V in apical membranes of placental villi is quantitatively reduced by antiphospholipid antibody immunoglobulin G. STUDY DESIGN: Placentas were obtained from an index patient with antiphospholipid syndrome with intrauterine growth restriction and from a patient with an uncomplicated pregnancy who were both delivered by cesarean section. Apical villous membranes were isolated and annexin-V levels were measured by enzyme-linked immunosorbent assay. We then studied the effects of antiphospholipid immunoglobulin G on placental villous apical annexin-V in vitro. Antiphospholipid immunoglobulin G was isolated from the sera of five different patients with antiphospholipid antibody syndrome along with five paired control immunoglobulin Gs. Short-term cultures were established from normal placental villi and were exposed to the antibodies, after which isolated apical membranes and culture media were immunoassayed for annexin-V levels. RESULTS: Measurements of apical membrane-associated annexin-V from the antiphospholipid placenta showed significantly less apical membrane-associated annexin-V than did the normal placenta (mean +/- SEM: 4.9 +/- 0.4 micrograms/gm villi for antiphospholipid placenta vs 10.2 +/- 0.6 micrograms/gm villi for control, p < 0.001, n = 4). Exposure of placental villous cultures to five different antiphospholipid immunoglobulin Gs for 24 hours resulted in significant reduction of the levels of apical membrane annexin-V (mean +/- SEM: 3.9 +/- 0.3 micrograms/gm villi) compared with paired controls (5.1 +/- 0.3 micrograms/gm villi, p = 0.02). Villi incubated with the different antiphospholipid immunoglobulin Gs had significantly less annexin-V in conditioned media (mean +/- SEM: 45.1 +/- 4.9 ng/gm villi) compared with the paired normal immunoglobulin G control levels (72.6 +/- 11.4 ng/gm villi, p = 0.03). CONCLUSIONS: Antiphospholipid immunoglobulin G reduces the levels of syncytiotrophoblast apical membrane-associated annexin-V in placental villi and the release of annexin-V into surrounding media. Reduction of this anticoagulant protein at the maternal-fetal interface may account for the pregnancy loss observed in patients with antiphospholipid syndrome. Short-term culture of placental villi may offer an in vitro model to further study the mechanism of this effect of antiphospholipid antibodies.

Adult↗
PubMed1997

The effect of pregnancy on cyclosporine levels in renal allograft patients.

OBJECTIVE: To assess the effects of pregnancy on cyclosporine levels in six renal allograft patients. METHODS: Maternal demographic, laboratory, clinical, and perinatal outcome data were recorded in six pregnant women with previous renal allografts receiving cyclosporine immunosuppression. The cyclosporine and serum creatinine levels were measured before pregnancy, during each trimester, and postpartum. RESULTS: The mean (standard deviation [SD]) maternal age was 29.1 (3.8) years. Parity ranged from 0 to 3. Mean serum creatinine levels tended to be lower during pregnancy than before or after, as did the mean cyclosporine levels. After adjusting for dose, five of six patients had declines in cyclosporine level during pregnancy. The mean (SD) gestational age at delivery was 37.5 (2.8) weeks with a mean (SD) birth weight of 2837 (538) g. CONCLUSION: Pregnancy in patients with renal allografts can lead to a substantial decline in cyclosporine levels.

Adult↗
PubMed1997

Morbidity in the preterm infant with mature lung indices.

This study was designed to evaluate neonatal morbidity and mortality following preterm delivery in the setting of mature amniotic fluid pulmonary studies. We performed a retrospective analysis of all pregnancies resulting in preterm deliveries (< 37 weeks) from 1/1/88 to 5/31/92 in which there was a "mature" phospholipid profile, defined as positive phosphatidylglycerol (PG) or lecithin/sphyngomyelin (L/S) ratio > or = 2 determined within 1 week of delivery. Excluded were multiple gestations, diabetic pregnancies, and fetal or neonatal abnormalities involving the cardiovascular, renal, or pulmonary tract. Main outcome measures were incidence of significant neonatal morbidity, including respiratory distress requiring respiratory support, sepsis, patent ductus arteriosus, grade 3-4 intraventricular hemorrhage, necrotizing enterocolitis, retinopathy of prematurity, meningitis, and pneumonia. A total of 153 patients fulfilled the inclusion criteria. Mean (SD) gestational age at delivery and birth weight were 33.8 (2.1) weeks and 2298 (561) g, respectively. There were no neonatal deaths, but significant morbidity was present in 20% (31/153) of cases. The most common major neonatal complications were respiratory distress (12%) and suspected or documented sepsis (16%). Univariate analysis showed that frequency of major neonatal morbidity was related to gestational age at delivery (p < 0.001), birth weight (p < 0.001), Apgar score at 5 minutes < 7 (p = 0.008) and method of lung maturity assessment (complications were ore frequent when lung maturity was defined by L/S > or = 2 than by PG positivity) (p = 0.02). Multivariate analysis demonstrated a significant association between the presence of a neonatal complication and method of lung maturity assessment after adjustment for gestational age at delivery (p = 0.04). The incidence of major neonatal complications among preterm infants is high even in the presence of mature fetal lung studies; this incidence is related primarily to the gestational age at birth, and secondarily to the method of lung maturity testing (complications are less common in the presence of PG positivity than of L/S > or = 2).

Amniotic Fluid↗