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Biomedical subjects

R K Silver

Publications and source records attributed to R K Silver.

At least 19 recordsLinked to original sources

Psychosocial assessment by phone for high-scoring patients taking the Edinburgh Postnatal Depression Scale: communication pathways and strategies.

The well-documented risks associated with perinatal depression provide a strong argument for universal screening. However, uncertainty about what to do with findings is a significant barrier to implementing screenings where obstetric care is provided. Based on experience with a comprehensive screening program, we describe a protocol for those critical communication pathways that encourage a dynamic phone exchange between a mental health caller and the patient who has scored in the high range on the Edinburgh Postnatal Depression Scale. In addition, we present guidelines for developing an action plan for addressing intervention needs and closing the feedback loop to the original administrators of the scale.

Adult↗

Late first-trimester invasive prenatal diagnosis: results of an international randomized trial.

OBJECTIVE: To assess, in a randomized trial, the safety and accuracy of amniocentesis and transabdominal chorionic villus sampling (CVS) performed at 11-14 weeks of gestation, given that this time frame is increasingly relevant to early trisomy screening. METHODS: We compared amniocentesis with CVS from 77 to 104 days of gestation in a randomized trial in a predominantly advanced maternal age population. Before randomization, the feasibility of both procedures was confirmed by ultrasonography, and experienced operators performed sampling under ultrasound guidance; conventional cytogenetic analysis was employed. The primary outcome measure was a composite of fetal loss plus preterm delivery before 28 weeks of gestation in cytogenetically normal pregnancies. RESULTS: We randomized 3,775 women into 2 groups (1,914 to CVS; 1,861 to amniocentesis), which were comparable at baseline. More than 99.6% had the assigned procedure, and 99.9% were followed through delivery. In contrast to previous thinking, in the cytogenetically normal cohort (n = 3,698), no difference in primary study outcome was observed: 2.1% (95% confidence interval 1.5, 2.8) for CVS and 2.3% (95% confidence interval, 1.7, 3.1) for amniocentesis. However, spontaneous losses before 20 weeks and procedure-related, indicated terminations combined were increased in the amniocentesis group (P =.07, relative risk 1.74). We found a 4-fold increase in the rate of talipes equinovarus after amniocentesis (P =.02) overall and in week 13 (P =.03, relative risk = 4.65), but data were insufficient to determine this risk in week 14. CONCLUSION: Amniocentesis at 13 weeks carries a significantly increased risk of talipes equinovarus compared with CVS and also suggests an increase in early, unintended pregnancy loss. LEVEL OF EVIDENCE: I

Abortion, Induced↗

First-trimester trisomy screening: nuchal translucency measurement training and quality assurance to correct and unify technique.

OBJECTIVE: To describe the process of training for measuring nuchal translucency at five clinical centers in North America and to evaluate methods of quality assurance and feedback. DESIGN: Throughout a period of 18 months, the performance of sonographers in measuring fetal nuchal translucency was monitored using qualitative and quantitative methods of review. After 12 months, different approaches (written and personal feedback) were used to inform sonographers of technical aspects that needed to or could be improved. RESULTS: On initial qualitative review, discrepancies in judgment from different reviewers coincided with suboptimal magnification, failure to visualize the amniotic membrane and/or use of cross-shaped calipers. At subsequent global review, 13 (29%) images of nuchal translucency measurements were considered unacceptable. Quantitative assessment revealed that, during the first part of the study, the means from four sonographers were significantly smaller and the mean from the fifth sonographer was significantly larger than expected on the basis of findings from The Fetal Medicine Foundation (P < 0.0001). Following feedback, sonographers who underestimated nuchal translucency and who received a written report only did not change measurements overall (P = 0.9759). In contrast, those who received additional intervention showed a marked difference (P < 0.0001). CONCLUSIONS: Global qualitative review of images from one sonographer may be preferable to assessment of individual aspects of images. Results from global qualitative review correspond well with findings from quantitative analysis, indicating that the latter can be applied for ongoing audit. Observation of divergent results should prompt extensive personal feedback, rather than a written report, to prevent sonographers from settling in their own, inappropriate technique.

Allied Health Personnel↗

Lamellar body counts compared with traditional phospholipid analysis as an assay for evaluating fetal lung maturity.

OBJECTIVE: To compare lamellar body counts with the lecithin/sphingomyelin ratio and phosphatidylglycerol analysis in terms of assessment of risk of respiratory distress syndrome (RDS). METHODS: Lamellar body counts, lecithin-sphingomyelin ratios (L/Ss), and phosphatidylglycerol levels were assessed in 1611 amniotic fluid samples obtained at four clinical sites from pregnant women whose fetuses were at risk for RDS. Cases in which delivery occurred within 72 hours of sample collection (n = 833) were analyzed. Specific cutoffs for predicting the likelihood of RDS for both the lamellar body count and the L/S had been derived previously at each of the clinical sites based on receiver operating characteristic curves using unrelated samples, whereas phosphatidylglycerol was reported as either mature (present) or immature (absent). Standard clinical and radiographic criteria were used to diagnose RDS, and the diagnosis was confirmed by review of newborn records. RESULTS: One hundred (12.0%) of the 833 infants delivered within 72 hours of sample collection developed RDS. The negative predictive value of the lamellar body count (97.7%) was similar to that of the L/S (96.8%) and slightly better than that of phosphatidylglycerol analysis (94.7%) (P =.048). The lamellar body count performed as well as phospholipid analysis irrespective of gestational age or patient population. CONCLUSION: The lamellar body count compares favorably with traditional phospholipid analysis as an assay for assessment of fetal lung maturity. Lamellar body counts are preferable because they are faster, more objective, less labor intensive, less technique dependent, and less expensive and because they can be performed with equipment available in every hospital laboratory.

Amniocentesis↗

Immunologic studies in presumed amniotic fluid embolism.

OBJECTIVE: To evaluate the potential role of immunologic mechanisms that involve mast cell degranulation (anaphylaxis) or complement activation in the mechanism of amniotic fluid embolism. METHODS: This study was a case series of nine women with presumed amniotic fluid embolism and a control group of 22 women who had normal labor. Women were from community and tertiary referral hospitals in Japan and the United States. Main outcome measures were maternal peripartum complement levels (C3 and C4), serum levels of tryptase, urinary histamine concentrations, and serum levels of a fetal antigen (sialyl Tn). RESULTS: Serum tryptase and urinary histamine measurements were negative in women with amniotic fluid embolism; seven of nine had elevated levels of fetal antigen. All eight who had serum available for testing had abnormally low levels of complement. Mean C3 level of 44.0 mg/dL and C4 level of 10.7 mg/dL were significantly lower than corresponding postpartum control values of 117.3 mg/dL and 29.4 mg/dL (P =.018 for C3, P =.012 for C4). Postpartum C3 and C4 levels decreased by 8% and 5%, respectively, compared with intrapartum values (P =.003 for C3, P =.021 for C4) but were still within normal range. CONCLUSION: Serologic findings suggest a role for complement activation in the mechanism of amniotic fluid embolism. Laboratory data from this series did not implicate mast cell degranulation (anaphylaxis) in the pathophysiology of the disease.

Antigens, Tumor-Associated, Carbohydrate↗

A reappraisal of amniotic fluid alpha-fetoprotein measurement at the time of genetic amniocentesis and midtrimester ultrasonography.

OBJECTIVE: To evaluate the contemporary utility of amniotic fluid alpha-fetoprotein measurement as a complementary test for fetal abnormalities at the time of invasive genetic testing. METHODS: A review of amniotic fluid alpha-fetoprotein test results was conducted to determine the frequency with which elevated alpha-fetoprotein values added independent diagnostic information and altered clinical management. Amniotic fluid specimens processed for alpha-fetoprotein between 1995 and 1998 were included. Elevated alpha-fetoprotein cases were classified as either incidental to the fetal abnormality diagnosed or central to the identification of a fetal anomaly on the basis of whether an ultrasonographic examination had already identified the anomaly before amniocentesis. The costs associated with alpha-fetoprotein testing were used to estimate the expenditure per pregnancy in which elevated alpha-fetoprotein values would add discriminatory diagnostic value. A hypothetical national cost model was constructed to explore the utility of selective rather than routine amniotic fluid alpha-fetoprotein measurement. RESULTS: Eighty-two (3%) of 2769 amniotic fluid alpha-fetoprotein values were elevated. In only 1 instance was the elevated result found to be partially discriminatory (e.g., an established diagnosis of microcephaly with an associated small encephalocele identified after the elevated amniotic fluid alpha-fetoprotein value prompted repeated ultrasonographic assessment). Sixty-one other neural tube defects were detected by ultrasonography alone (myelomeningocele, n = 28; anencephaly, n = 24; and encephalocele, n = 9). Thus, an elevated alpha-fetoprotein result added diagnostic precision in only 1 (0.036%) of 2769 cases. Cost estimates suggested that routine amniotic fluid alpha-fetoprotein assessment resulted in a $219,000 expenditure per informative case. CONCLUSIONS: Routine measurement of amniotic fluid alpha-fetoprotein during amniocentesis may not be warranted in centers with expertise in targeted ultrasonographic imaging.

Adolescent↗

A multicenter, placebo-controlled pilot study of intravenous immune globulin treatment of antiphospholipid syndrome during pregnancy. The Pregnancy Loss Study Group.

OBJECTIVE: Treatment with heparin and low-dose aspirin improves fetal survival among women with antiphospholipid syndrome. Despite treatment, however, these pregnancies are frequently complicated by preeclampsia, fetal growth restriction, and placental insufficiency, often with the result of preterm birth. Small case series suggest that intravenous immune globulin may reduce the rates of these obstetric complications, but the efficacy of this treatment remains unproven. This pilot study was undertaken to determine the feasibility of a multicenter trial of intravenous immune globulin and to assess the impact on obstetric and neonatal outcomes among women with antiphospholipid syndrome of the addition of intravenous immune globulin to a heparin and low-dose aspirin regimen. STUDY DESIGN: This multicenter, randomized, double-blind pilot study compared treatment with heparin and low-dose aspirin plus intravenous immune globulin with heparin and low-dose aspirin plus placebo in a group of women who met strict criteria for antiphospholipid syndrome. All patients had lupus anticoagulant, medium to high levels of immunoglobulin G anticardiolipin antibodies, or both. Patients with a single live intrauterine fetus at </=12 weeks' gestation were randomly assigned to receive either intravenous immune globulin (1 g/kg body weight) or an identical-appearing placebo for 2 consecutive days each month until 36 weeks' gestation in addition to a heparin and low-dose aspirin regimen. Maternal characteristics, obstetric complications, and neonatal outcomes were compared with the Student t test and the Fisher exact test as appropriate. RESULTS: Sixteen women were enrolled during a 2-year period; 7 received intravenous immune globulin and 9 were given placebo. The groups were similar with respect to age, gravidity, number of previous pregnancy losses, and gestational age at the initiation of treatment. Obstetric outcomes were excellent in both groups, with all women being delivered of live-born infants after 32 weeks' gestation. The rates of antepartum complications such as preeclampsia, fetal growth restriction, and placental insufficiency (as manifested by fetal growth restriction or fetal distress) were similar between the 2 groups. Gestational age at delivery (intravenous immune globulin group, 34.6 +/- 1.1 weeks; placebo group, 36.7 +/- 2.1 weeks) and birth weights (intravenous immune globulin group, 2249.7 +/- 186.1 g; placebo group; 2604.4 +/- 868.9 g) were similar between the 2 groups. There were fewer cases of fetal growth restriction (intravenous immune globulin group, 0%; placebo group, 33%) and neonatal intensive care unit admission (intravenous immune globulin group, 20%; placebo group, 44%) among the infants in the intravenous immune globulin group than those in the placebo group, but these differences were not significant. CONCLUSION: A multicenter treatment trial of intravenous immune globulin is feasible. In this pilot study intravenous immune globulin did not improve obstetric or neonatal outcomes beyond those achieved with a heparin and low-dose aspirin regimen. Although not statistically significant, the findings of fewer cases of fetal growth restriction and neonatal intensive care unit admissions among the intravenous immune globulin-treated pregnancies may warrant expansion of the study.

Adult↗

Timing of labor induction after premature rupture of membranes between 32 and 36 weeks' gestation.

OBJECTIVE: The objective was to determine a consensus gestational age for labor induction after premature rupture of membranes between 32 and 36 weeks' gestation on the basis of the relative frequencies of adverse neonatal outcomes. STUDY DESIGN: A retrospective review was undertaken of all patients with premature rupture of membranes between 32 and 36 weeks' gestation. These patients were managed expectantly whenever possible. Neonatal outcomes were stratified by gestational age at rupture of membranes. RESULTS: Two hundred thirty-six patients with rupture of membranes between 32 and 36 weeks' gestation were managed expectantly. Prolongation of pregnancy by >/=1 week was infrequent in all cases, particularly if membrane rupture occurred after 34 weeks' gestation. Reductions in the neonatal length of stay and the incidence of hyperbilirubinemia were observed at 34 weeks' gestation with respect to younger gestational ages. No perinatal deaths occurred among the study cases. CONCLUSIONS: A "break point" in neonatal morbidity was observed at 34 weeks' gestation, which supports induction of labor at this gestational age. The short latencies observed limit the potential benefits of expectant management.

Adult↗

Clinical implications of atypical chromosome abnormalities diagnosed prenatally.

OBJECTIVE: To determine the frequency of atypical aneuploidy resulting from prenatal testing and assess the implications of these diagnoses on prenatal decision making. METHODS: We reviewed all amniotic fluid and chorionic villus samples obtained between January 1994 and September 1997 and grouped the abnormal cases into typical or atypical subcategories. This distinction was based upon whether the diagnosis provided a straightforward range of prognoses or an ambiguous clinical implication. Results were stratified by sample source to determine whether atypical aneuploidy was more commonly seen in cultures of chorionic villi or amniocytes. We also evaluated the influence of ultrasound findings on prenatal decision making in atypical aneuploid cases. RESULTS: Of 2960 samples, 134 were abnormal (4.4%), with 27 of 134 abnormalities (20%) representing atypical aneuploidies. The percentages of chorionic villus and amniocentesis cases complicated by atypical aneuploidy (22% and 78%, respectively) were consistent with the distribution of procedures in the entire study. Ultrasound abnormalities did not invariably prompt a decision to terminate pregnancy (only two terminations of six fetuses with congenital malformation), whereas atypical karyotypes led to termination even in the presence of normal-appearing fetal anatomy (five terminations of 21 without malformations; P = .63). CONCLUSION: The frequency of atypical aneuploidy resulting from prenatal diagnosis was approximately 1.0%, and these cases represented 20% of all abnormal karyotypes observed. The ambiguity conferred by atypical aneuploidy can influence a family's decision making, even in the presence of normal ultrasound findings.

Adult↗

Optional vaginal delivery rate. An informative indicator of intrapartum care.

OBJECTIVE: To determine whether an "optional" vaginal delivery rate and novel delivery score would provide informative profiles of intrapartum care. STUDY DESIGN: Prospective survey of all parturients delivering between January and December 1996. Deliveries were categorized as standard-vaginal (V-S), optional-vaginal (V-O), standard-cesarean (C-S) or potentially avoidable-cesarean (C-PA) using specific perinatal criteria derived from the literature. A weighted equation was developed and applied, generating physician delivery scores, giving "extra credit" for V-O and a "debit" for C-PA: delivery score = [(% V-O x 2) + (% V-S) - (% C-PA] x 100. RESULTS: V-O rates and delivery scores ranged from 0% to 25% and from 52 to 113, respectively (medians of 9.8% and 92.9). Among the obstetricians (n = 38), a significant inverse correlation was noted between the total C-S rates and V-O rates (r = -.54, P < .005). The maternal-fetal medicine physicians (n = 6) had high total C-S rates (22-36%) but also had high V-O rates (17.1-23.5%) and high delivery scores (82.1-101.5). CONCLUSION: The optional vaginal delivery rate and delivery score are more-informative indicators of intrapartum management acumen than is cesarean section rate alone. We suggest incorporating these descriptors into departmental quality assurance programs.

Adult↗

Neonatal outcomes in triplet gestations after a trial of labor.

OBJECTIVE: This study aimed to compare neonatal outcomes in a cohort of triplet gestations undergoing a trial of labor with those of a similar cohort delivered by elective cesarean delivery. STUDY DESIGN: Thirty-three women with triplet gestations who underwent a trial of labor were compared with a matched cohort of 33 women with triplet gestations who were delivered of their infants by elective cesarean delivery. Neonatal outcomes assessed included respiratory distress syndrome, retinopathy of prematurity, necrotizing enterocolitis, intraventricular hemorrhage, Apgar scores, and birth trauma. RESULTS: Twenty-nine of 33 women (87.9%) who underwent a trial of labor had a successful vaginal delivery of all 3 neonates. One patient was delivered of her first triplet vaginally but then required a cesarean delivery for abruptio placentae; 3 other patients were delivered of their infants by cesarean section for active-phase arrest of labor. There were no differences in neonatal outcomes between the 2 groups, although triplet neonates delivered by elective cesarean section demonstrated a trend toward a greater incidence of respiratory distress syndrome (P = .09). CONCLUSION: Our experience suggests that offering vaginal delivery is an acceptable management plan for triplet gestations.

Adult↗

Midtrimester amniocentesis. Influence of operator caseload on sampling efficiency.

OBJECTIVE: To evaluate the impact of operator caseload on the sampling efficiency for early and standard, midtrimester amniocentesis. STUDY DESIGN: Prospective ascertainment of genetic amniocenteses performed during 36 months, grouped into early (13-14 weeks' gestation) and standard procedures (15-20 weeks' gestation). Details of each amniocentesis were recorded immediately after sampling, and pregnancy outcomes were retrieved via questionnaires completed by the delivering physician. Sampling efficiency was evaluated separately in the early and standard cohorts in relation to operator caseload. RESULTS: In total, 193 and 707 patients underwent early and standard amniocentesis, respectively. Forty of 46 physician-operators performed < 50 total procedures during the study interval (group A). When compared to operators performing > or = 50 cases (group B, n = 6), a higher rate of single-pass success was noted among group B physicians for both early and standard procedures (A vs. B, early: 40/45 vs. 145/148, P = .018; standard: 243/295 vs. 384/412, P < .0001). Logistic regression confirmed an independent effect of physician caseload on sampling efficiency and a significant interaction between physician caseload and simultaneous ultrasound guidance in predicting single-attempt success. CONCLUSION: Operator caseload directly influenced sampling efficiency for both early and standard, midtrimester amniocentesis.

Adult↗

Perinatal outcome associated with outpatient management of triplet pregnancy.

OBJECTIVE: Our goal was to compare the lengths of hospitalization and the perinatal outcomes of triplet pregnancies managed with either outpatient or inpatient third-trimester bed rest. STUDY DESIGN: Thirty-two triplet pregnancies in which outpatient bed rest was prescribed (April 1993 to April 1996) were compared with a historic cohort of 34 triplets (January 1985 to March 1993) in which routine hospitalization was undertaken in the third trimester. Length of hospitalization and maternal and neonatal outcome parameters were compared between groups. RESULTS: Maternal inpatient hospital days were significantly reduced for the group managed as outpatients, but combined maternal and neonatal hospitalization was similar between groups. The mean gestational age at delivery was 1 week greater in the hospitalized cohort (33.5+/-2.8 vs 32.5+/-2.8, respectively; p=0.16), and average birth weight was correspondingly greater in hospitalized cases (1942 gm vs 1718 gm, p < 0.005). Neonatal lengths of stay were similar between groups, reflecting earlier postnatal discharge in the outpatient era of this study. Preeclampsia occurred with greater frequency in the outpatient group (31.3% vs 8.8%, p=0.02), and the neonatal complication of intraventricular hemorrhage occurred more commonly in this cohort as well (10/96 vs 1/102, p=0.004). All other maternal and neonatal complications were similar between groups. CONCLUSION: Reduction in the length of hospitalization attributable to outpatient management was limited to the maternal length of stay. It is possible that the observed maternal and neonatal complications in the outpatient group may have been related to less rigorous bed rest. We would suggest that the differences noted in preeclampsia, birth weight, and intraventricular hemorrhage support prospective evaluation of bed rest in triplet pregnancy.

Adult↗

Multifetal reduction increases the risk of preterm delivery and fetal growth restriction in twins: a case-control study.

OBJECTIVE: To compare pregnancy outcome in twin gestations resulting from multifetal reduction to "primary" twin pregnancies derived from either spontaneous conception or infertility therapy. DESIGN: Case-control study. SETTING: University-affiliated tertiary center. PATIENT(S): Multifetal pregnancies (quadruplets or more) reduced to twins (group A) compared with twin gestations conceived either spontaneously (group B) or through infertility therapy (group C). INTERVENTION(S): Multifetal reduction for group A; perinatal care for groups A, B, and C. MAIN OUTCOME MEASURE(S): Comparison of perinatal complications between groups including antepartum bleeding, premature membrane rupture, and preterm labor. Neonatal outcomes compared including gestational age at delivery, birth weight, incidence of fetal growth restriction, and twin discordancy. RESULT(S): A higher incidence of idiopathic preterm labor was noted in group A cases (14/18) compared with either of the control groups (B: 26/54, or C: 24/54). As a consequence, group A had the lowest gestational age at delivery (32.6 +/- 3.9 weeks) compared with groups B (33.6 +/- 4.4 weeks) and C (36.0 +/- 3.4 weeks). Corresponding birth weights of both first- and second-born twins were significantly lower in group A compared with group C, whereas the birth weight comparison between groups A and B showed a nonsignificant difference. The proportion of pregnancies in which one or both twins weighted less than the 10th percentile was greatest in group A pregnancies (A: 5/18 versus C: 5/54). Discordant birth weight among twin pairs was proportionately greater for group A cases at both the 20% and 30% discordance levels. CONCLUSION(S): Twin gestations resulting from multifetal reduction are at increased risk for preterm birth, fetal growth restriction, and discordancy when compared with fertility therapy-derived, nonreduced twins.

Adult↗

Randomized trial of antenatal dexamethasone in surfactant-treated infants delivered before 30 weeks' gestation.

OBJECTIVE: To determine if an additive effect exists between antenatal corticosteroid administration and postnatal surfactant therapy in the prevention of respiratory distress syndrome (RDS) in preterm infants. METHODS: A randomized, double-blind trial was conducted from April 1990 to June 1994, in which dexamethasone (5 mg every 12 hours for a total of four doses) or saline was given to women at risk for delivery at 24-29 weeks' gestation. At birth, prophylactic surfactant was administered to all study infants. Main outcome measures were RDS occurrence and severity. Secondary clinical end points included bronchopulmonary dysplasia, pneumothorax, patent ductus arteriosus, necrotizing enterocolitis, retinopathy, intraventricular hemorrhage, and death. RESULTS: Seventy-five of the 124 randomized subjects delivered 96 infants within the studied gestational age range (dexamethasone, n = 54; placebo, n = 42). Similar maternal demographics and obstetric complications were noted between study groups. A greater population of infants were delivered from multi-fetal gestations in the dexamethasone cohort (26 of 54 versus 12 of 42 newborns; P = .05). There were no significant differences in the occurrence or severity of RDS between the dexamethasone and placebo infants (none or mild, 67 versus 67%; moderate, 24 versus 26%; severe, 9 versus 7%, respectively), or differences in any of the secondary clinical outcomes. The study size was sufficient to exclude a 50% reduction in RDS incidence as a consequence of dexamethasone exposure. An analysis restricted to singletons (dexamethasone, n = 28; placebo, n = 30) revealed similar overall occurrence of intraventricular hemorrhage (12 of 28 versus ten of 30; P = .63), but significantly fewer grade 3 and 4 intraventricular hemorrhages in dexamethasone-exposed neonates (two of 12 versus six of ten; P = .048). CONCLUSION: Antenatal dexamethasone does not appear to decrease the incidence or severity of RDS in surfactant-treated infants delivered at 24-29 weeks' gestation, but may be associated with reduced severity of intraventricular hemorrhages in surfactant-treated singletons in this gestational age range.

Adult↗

Evaluation of nitric oxide as a mediator of severe preeclampsia.

OBJECTIVE: Our purpose was to determine whether a reduction in nitric oxide synthesis occurs in women with severe preeclampsia as a consequence of soluble serum factors. STUDY DESIGN: Circulating nitrate and nitrite levels were compared between women who met standard clinical criteria for severe preeclampsia (n = 21) and maternal or gestational age-matched, normotensive, primagravid control subjects (n = 21). End-products of nitric oxide synthesis were measured from venous blood samples using nitrate reduction and chemiluminescence. To detect in vitro suppression of nitric oxide synthesis, human umbilical vein endothelial cell monolayers were grown to confluence and exposed to culture media containing 20% severe preeclamptic or control sera. Nitrate and nitrite production were compared in duplicate monolayers for each experimental condition, expressed as means +/- SEM in picomoles per 10(6) cells. Data were compared by Student's t or Mann-Whitney U tests, when appropriate, along with Spearman correlations for comparisons of laboratory and clinical data. RESULTS: Circulating nitrate and nitrite levels were similar in normotensive and preeclamptic cohorts (976 +/- 88 vs 1009 +/- 41 pmol/ml, respectively; p = 0.22), and no correlations between blood pressure and nitric oxide metabolite levels were observed for the control or severely preeclamptic subsets. Similar patterns of in vitro endothelial nitrite production were observed after 1-, 12-, and 24-hour incubations with 20% control or preeclamptic sera. CONCLUSIONS: Circulating nitrate and nitrite levels are not reduced in patients with severe preeclampsia compared with normotensive controls, and sera from these women do not suppress endothelial cell nitric oxide synthesis in vitro.

Adult↗

Inducible platelet adherence to human umbilical vein endothelium by anticardiolipin antibody-positive sera.

OBJECTIVE: Our purpose was to determine whether anticardiolipin antibody-positive sera alter platelet adherence to vascular endothelium by a platelet activating factor-dependent mechanism. STUDY DESIGN: Anticardiolipin antibody-positive sera were used in an in vitro platelet-endothelial adherence assay. Confluent endothelial monolayers were randomly assigned for exposure to a 20% concentration of experimental and control sera. Platelets were radiolabeled with chromium 51, and adherence was assessed by quantification of endothelium-associated gamma emission. RESULTS: Inducible platelet adherence was observed by endothelial cell preincubation with sera from anticardiolipin antibody-positive donors compared with anticardiolipin antibody-negative control experiments (n = 12, platelet adherence 6.4% +/- 1.3% vs 4.5% +/- 1.1%, respectively; p = 0.02). Compared with endothelial cell incubations alone, coincubation of platelets with anticardiolipin antibody-positive sera consistently augmented primary adherence (n = 6, p = 0.042). Furthermore, platelet-adherence induced by antibody-positive sera was consistently attenuated by specific platelet-activating factor antagonists in a dose-dependent fashion (p < 0.001) and was restored by exogenously administered platelet-activating factor. CONCLUSIONS: Anticardiolipin antibody-induced platelet adherence may constitute an important prerequisite for vascular thrombosis in antibody-positive patients. The findings from this in vitro model suggest direct involvement of platelet-activating factor in this process.

Antibodies, Anticardiolipin↗