Biomedical subjects

C J Lockwood

Publications and source records attributed to C J Lockwood.

At least 127 records · Page 7Linked to original sources

PubMed1993

Amniocentesis and chorionic villus sampling.

Amniocentesis performed at 16 to 18 weeks' gestation has been the gold standard approach for prenatal cytogenetic diagnosis. Over the past few years, large collaborative studies on chorionic villus sampling have confirmed the safety and efficacy of chorionic villus sampling as a viable alternative for women seeking prenatal diagnosis. While the expanding experience with chorionic villus sampling has answered questions regarding the safety of the transabdominal approach, it has also raised questions concerning possible associations with limb abnormalities, its usefulness in multiple gestations, and the clinical significance of confined placental mosaicism. These issues, as well as the technical and gestational age limitations of chorionic villus sampling, have led many investigators to study the technical feasibility, safety, and accuracy of amniocentesis performed in the first trimester or early second trimester. While this approach appears both safe and efficacious, there are concerns regarding orthopedic abnormalities and the reliability of first-trimester amniotic fluid acetylcholinesterase and alpha-fetoprotein levels in the diagnosis of neural tube defects.

Abortion, Spontaneous↗

PubMed1992

Morbidity of failed labor in patients with prior cesarean section.

OBJECTIVE: The aim of our study was to determine whether the reported increased morbidity associated with failed attempted vaginal birth after cesarean section is attributable to the presence of a uterine scar alone or to labor preceding a cesarean section. STUDY DESIGN: Primiparous women (N = 237) who underwent repeat cesarean section after a failed trial of vaginal birth after cesarean section were retrospectively compared with 1582 nulliparous women who underwent a primary cesarean section after a failed trial of labor. RESULTS: There were no significant differences in maternal or neonatal morbidity between the two groups except for an increase in the prevalence of thin meconium in patients undergoing primary cesarean section. CONCLUSION: Our results suggest that the presence of a previous cesarean section scar does not increase the overall baseline morbidity associated with cesarean section after labor.

Adult↗

PubMed1992

Beta-endorphin concentrations in fetal blood during the second half of pregnancy.

OBJECTIVE: Endogenous opiates may play a role in both fetal physiologic functions and the adaptation to intrauterine stress. However, our understanding of this role is hampered by an absence of data on circulating levels of these substances during fetal life. STUDY DESIGN: We measured serum beta-endorphin values with a radioimmunoassay in 81 paired fetal and maternal blood samples and 24 neonatal cord specimens. The former samples were uneventfully obtained from uncomplicated pregnancies between 18 and 39 weeks of gestation at the time of cordocentesis for prenatal diagnosis. RESULTS: Mean fetal beta-endorphin concentrations were significantly lower than beta-endorphin values from neonates (90.5 pg/ml [+/- 59.4] vs 228.4 pg/ml [+/- 166.2]; p less than 0.001), but significantly higher than mean maternal values (70.5 pg/ml [+/- 48.8]; p less than 0.02). Although fetal beta-endorphin levels decreased between 18 and 28 weeks' gestation, the correlation between fetal beta-endorphin values and gestational age was not significant (r = -0.193; p = 0.07). However, fetal beta-endorphin concentrations were significantly correlated with maternal values (Spearman's rank r = 0.47; p less than 0.001). CONCLUSION: These findings suggest that delivery or fetal adaptation to an extrauterine environment is associated with significant increases in beta-endorphin release. Moreover, although the fetal pituitary may be the primary source of circulating fetal beta-endorphin, a maternal or placental contribution cannot be excluded. Our data identify a physiologic range for fetal beta-endorphin concentrations.

Female↗

PubMed1992

Clinical significance and sonographic diagnosis of velamentous umbilical cord insertion.

In order to evaluate the clinical significance of velamentous cord insertion (VCI) and the role of ultrasound in its diagnosis, all 82 cases of VCI during January 1985 to January 1989 at the Mount Sinai Medical Center were reviewed. The overall rate of VCI in our study (0.5%) was similar to that of previous reports. Pregnancy outcomes in VCI patients with 77 singleton gestations were compared with a control group of 15,865 patients. In contrast to the existing literature, multiparity and prior cesarean section deliveries were not increased in pregnancies with VCI. The VCI group had more intrapartum complications and a lower birthweight than the controls. Routine nontargeted obstetric ultrasound failed to detect any cases of VCI, including three cases of vasa previa. Since VCI was not identified prenatally and many of its sequelae are readily identifiable only during the intrapartum period, the potential for preemptive obstetric intervention appears to be limited. In addition, failure to diagnose apparent VCI during a routine ultrasound does not appear to be a departure from the standard of care.

Adult↗

PubMed1992

The severely anemic and hydropic isoimmune fetus: changes in fetal hematocrit associated with intrauterine death.

Hydrops caused by isoimmune hemolytic anemia is frequently associated with fetal death following intrauterine intravascular transfusion. To identify possible predictors of procedure-related fetal death, we examined changes in fetal blood volume and hematocrit resulting from the initial transfusion performed on 19 severely anemic, hydropic fetuses. Seven fetuses (36.8%) died at 24-72 hours after transfusion, but in no case was the procedure associated with fetal distress. There were no significant differences between fetuses who died and those who survived in terms of total volume of blood transfused, volume transfused as a percentage of total fetoplacental blood volume, hematocrit of transfused blood, post-transfusion hematocrit, umbilical vein pH, or gestational age at transfusion. Significant differences were noted between hydropic fetuses who died compared with those who survived in the mean pretransfusion hematocrit, 6.7% (+/- 2.0) versus 8.7% (+/- 1.6) (P = .03), and the relative increase in post- over pre-transfusion hematocrit, 5.5-fold (+/- 1.4) versus 3.5-fold (+/- 0.8) (P = .001). Stepwise logistic regression analysis confirmed that only the relative increase in hematocrit was predictive of fetal loss. Moreover, six of seven fetal deaths occurred when the relative increase in hematocrit was greater than fourfold, whereas ten of 12 surviving fetuses had relative increases of less than fourfold. We conclude that large, acute increases in fetal hematocrit following intrauterine transfusion are associated with substantial mortality in hydropic fetuses.

Anemia↗

PubMed1992

Growth hormone and fibronectin expression in 3T3 preadipose cells.

In the present study we focused on the relationship between GH action and the extracellular matrix in 3T3-F442A preadipose cells. Results from Northern blotting indicated that in serum-free medium, the presence of 2 nM met-human GH down-regulated levels of fibronectin messenger RNA by approximately 40, 60, and 70% as compared with control levels on days 1, 2, and 4, respectively. GH-dependent reduction of levels of collagen alpha 1(I) mRNA expression occurred later and was less pronounced than effects on levels of fibronectin mRNA, suggesting a specificity in the matrix-altering function of GH. Western blot analyses and immunoprecipitation studies revealed that between 2 and 5 days of culture, matrix-associated fibronectin protein was reduced 70 to 90% by GH treatment. Down-regulation of fibronectin protein expression by met-human GH was dose-dependent between 2 and 0.02 nM. The presence of 2 nM insulin or insulin-like growth factor-1 promoted a 30-40% increase in fibronectin levels compared to control cells. The GH-promoted down-regulation of fibronectin expression was eliminated by concomitant addition of insulin. These data demonstrated that GH effects on matrix-associated fibronectin expression were independent of, and in opposition to, effects promoted by insulin and insulin-like growth factor-1. Treatment of culture dishes with fibronectin or collagen inhibited GH-stimulated adipogenesis 50 and 80%, respectively, compared with controls, as judged by levels of glycerol-3-phosphate dehydrogenase activity. Thus, composition of the extracellular matrix was a critical factor in GH-induced adipogenesis of 3T3-F442A fibroblasts. Our results demonstrate that GH action in 3T3 preadipose cells is intimately coupled to the biology of extracellular matrix.

3T3 Cells↗

PubMed1992

Hypoplastic pulmonary artery: an unusual entity mimicking pulmonary embolism during pregnancy.

Hypoplastic pulmonary artery is an unusual congenital malformation. We describe a case of hypoplastic pulmonary artery diagnosed during the third trimester of pregnancy. The clinical and radiologic features mimicked pulmonary embolism, including hemoptysis, chest pain, pleural effusion, mild hypoxemia, and a suggestive ventilation-perfusion scan. Accurate differentiation of this entity from pulmonary embolism is necessary to obviate the need for prolonged anticoagulation.

Adult↗

PubMed1992

Sonographic diagnosis of the large for gestational age fetus at term: does it make a difference?

We evaluated 406 women with late third-trimester ultrasound examinations to determine whether the sonographic diagnosis of a large for gestational age (LGA) fetus, defined as an estimated fetal weight at or above the 90th percentile, altered the management of labor and delivery. The sonographic prediction of LGA fetuses had a sensitivity, specificity, and positive predictive value of 50, 90, and 52%, respectively. Women without the sonographic diagnosis of an LGA fetus (N = 338) differed from those with the diagnosis (N = 68) in the frequency of diagnosed labor abnormalities (19 versus 30%, P = .03), use of epidural anesthesia (57 versus 74%, P = .01), and the incidence of cesarean deliveries (32 versus 53%, P = .004). To determine whether it was the sonographic prediction of an LGA fetus or the actual fetal weight that altered clinical management and perinatal outcomes, we stratified the study population into four groups and compared the true negatives with the false positives and the false negatives with the true positives. The incorrect sonographic diagnosis of an LGA fetus had a statistically significant effect on both the diagnosis of labor abnormalities (P = .04) and the incidence of elective cesareans (P = .04) in pregnancies with appropriate for gestational age birth weights.

Cesarean Section↗

PubMed1992

Maternal renal artery Doppler velocimetry in normotensive pregnancies and pregnancies complicated by hypertensive disorders.

Hypertensive disorders in pregnancy contribute to substantial maternal and perinatal morbidity and mortality. Clinically, these disorders are characterized by hypertension and proteinuria. However, these signs appear some time after the physiologic derangements have been initiated. The primary objectives of this study were as follows: 1) to establish baseline values for the maternal renal artery systolic-diastolic ratio (S/D) as a function of gestational age in normal pregnancies, and 2) to determine whether renal artery blood flow indices can accurately identify those pregnancies complicated by, or destined to develop, hypertensive disorders. Using a pulsed Doppler scanner, maternal renal artery duplex evaluation was performed in four groups of women: normotensive nonpregnant, normotensive pregnant, chronic hypertensive pregnant, and preeclamptic. In 30 normotensive pregnant women followed longitudinally, no change was noted in the renal artery S/D as gestational age advanced, with mean (+/- SD) values of 2.5 +/- 0.20 and 2.6 +/- 0.21 for the left and right sides, respectively. No clinically meaningful discriminations were detected when the four groups were compared. We conclude that maternal renal artery Doppler waveforms are not significantly altered by either pregnancy or hypertensive complications in pregnancy.

Female↗

PubMed1991

Fetal fibronectin in cervical and vaginal secretions as a predictor of preterm delivery.

BACKGROUND: Preterm delivery is the leading cause of neonatal mortality in the United States, but efforts to address the problem are hampered by the inability to predict accurately which pregnancies are at risk. We postulated that damage to the fetal membranes may release fetal fibronectin into the cervix and vagina, giving rise to a biochemical marker for preterm delivery. METHODS: We measured fetal-fibronectin concentrations in cervical and vaginal secretions, amniotic fluid, and maternal plasma with a sensitive immunoassay using the monoclonal antibody FDC-6. Immunohistochemical studies were used to determine the distribution of fetal fibronectin in the placenta and amniochorionic membranes and to ascertain its cell of origin. RESULTS: Women with uncomplicated pregnancies (n = 163) who delivered at term rarely had cervicovaginal fetal-fibronectin concentrations above 0.05 micrograms per milliliter between 21 and 37 weeks of gestation (11 of 267 cervical samples [4 percent] and 9 of 267 vaginal samples [3 percent]. High levels of fetal fibronectin were detected in amniotic fluid and in the cervical or vaginal secretions of 93.8 percent of the women with preterm rupture of membranes (n = 65). Cervical or vaginal fetal fibronectin was also present in 50.4 percent of the women with preterm uterine contractions and intact membranes (n = 117), and its presence identified the women who delivered before term (n = 60) with a sensitivity of 81.7 percent and a specificity of 82.5 percent. In the placenta and membranes, fetal fibronectin was found at points of contact with the uterine wall. CONCLUSIONS: The presence of cervicovaginal fetal fibronectin in the second and third trimesters of pregnancy identifies a subgroup of women who are at high risk for preterm delivery. This phenomenon may reflect the separation of the chorion from the decidual layer of the uterus, with the release of intact or degraded chorionic components of the extracellular matrix into the cervical and vaginal secretions.

Amniotic Fluid↗

PubMed1991

Ultrasonographic screening for the Down syndrome fetus.

The usefulness of ultrasonography in detecting fetuses with Down syndrome in the second trimester has been the subject of considerable debate during the past 3 years. Conflicting reports have led to increasing confusion about the subject in the medical community and among the public. A review of the existing literature indicates that structural malformations that are chiefly cardiac are present in half of Down syndrome fetuses but are not consistently found during routine second-trimester ultrasonography. Although excess posterior nuchal skin-fold thickness is frequently present in infants with Down syndrome, it is also not consistently identified during second-trimester ultrasonographic examinations. Studies evaluating the efficacy of screening programs that are based on femur length shortening associated with Down syndrome have revealed markedly discrepant intercenter results. Although variations in methods may account for some of the observed variability, the magnitude of femoral shortening in Down syndrome suggests that this measurement may be only marginally useful. In summary, antenatal ultrasonography will allow for the detection of only those fetuses with Down syndrome who have multiple characteristic phenotypic features or anomalies. Moreover, current second-trimester ultrasonography does not appear to be either sensitive enough specific enough to be used as a unique Down syndrome screening modality; however, it may be a useful adjunct to maternal age and serum biochemical markers in the assignment of risk for Down syndrome.

Biometry↗

PubMed1991

Amniotic fluid contains tissue factor, a potent initiator of coagulation.

A primary clinical manifestation of amniotic fluid embolism is coagulopathy. Prior studies have identified a poorly characterized yet potent procoagulant property in amniotic fluid that increases with gestational age. One possible source of procoagulant activity is tissue factor, a primary biologic initiator of coagulation. We used sensitive immunoassays and functional assays to identify substantial quantities of tissue factor antigen and tissue factor-specific procoagulant activity in amniotic fluid, which increased with gestational age. Moreover, tissue factor accounted for virtually all of the coagulant potential of amniotic fluid. Amniotic tissue factor appeared intact and membrane bound and, when reconstituted into synthetic microvesicles of optimal phospholipid content, displayed nearly full activity. Calcium chelation and sonication experiments suggested that the presence of inhibitors and the physical configuration of membrane-bound tissue factor in amniotic fluid might explain the modest reduction in tissue factor procoagulant activity relative to total antigen levels observed in vivo. We postulate that the substantial quantities of functionally active tissue factor in amniotic fluid account for the coagulation changes accompanying amniotic fluid embolism and could indirectly contribute to the characteristic hemodynamic derangements of amniotic fluid embolism.

Amnion↗

PubMed1991

Is oncofetal fibronectin a trophoblast glue for human implantation?

Using an antibody probe specific for the class of fibronectins that contain the oncofetal domain, it was shown that oncofetal fibronectin (onfFN) is present wherever trophoblasts make contact with extraplacental extracellular matrix (ECM). In normal human implantation sites, onfFN was localized to a highly specific region-the ECM connecting extravilous trophoblasts and trophoblastic cell columns to the uterine decidua. This same zone of onfFN was present in an analogous location in extrauterine gestations. Like these in vivo extravillous trophoblasts, isolated cytotrophoblasts in primary culture synthesized and secreted onfFN as they underwent differentiation. Furthermore, when cocultured with an ECM gel, cytotrophoblast aggregates deposited onfFN at cell-ECM contact sites, resembling early implanting trophoblasts in vivo. In the presence of cyclic AMP agonists, onfFN synthesis was inhibited markedly. It is concluded from these results that onfFN is a trophoblast protein that, under cAMP regulation, could mediate implantation and placental-uterine attachment throughout gestation.

Cells, Cultured↗

PubMed1990

Increased plasma levels of ED1+ cellular fibronectin precede the clinical signs of preeclampsia.

To evaluate alterations in fibronectin homeostasis in preeclampsia we measured the plasma concentrations of fibronectin bearing an extra type III domain in 33 preeclamptic and 36 control patients at varying gestational ages. This fibronectin variant is concentrated in the endothelium of blood vessels and has been shown to be released at sites of vascular injury. In addition, total circulating fibronectin levels, composed primarily of hepatic-derived fibronectin lacking the extra type III domain, were also determined. Significant elevations in the average circulating concentrations of fibronectin with an extra type III domain (5.5 micrograms/ml [95% confidence interval, 4.7,6.2] versus 3.2 micrograms/ml [95% confidence interval, 2.9,3.5]; p = 0.0001) as well as total fibronectin (387 micrograms/ml [95% confidence interval, 357,417] versus 327 micrograms/ml [95% confidence interval, 305,348]; p = 0.036) were observed in preeclamptic versus control patients. Significant elevations in fibronectin levels with an extra type III domain occurred in the first trimester before clinical evidence of preeclampsia. In addition, multivariate logistic regression demonstrated a 5.4-fold increase in the risk of preeclampsia with each 1 microgram/ml elevation in concentration of fibronectin with an extra type III domain. These findings lend support to the hypothesis that endothelial-vascular injury is a primary event in the genesis of preeclampsia.

Adult↗

PubMed1989

The efficacy of fetal sonographic biometry in Down syndrome screening.

Sonographic biometry has been proposed as a second-trimester Down syndrome screening modality. Approaches have relied on the apparent "shortened" femur length of fetuses with Down syndrome. Unfortunately, significant intercenter variation has been reported in the magnitude of this femur length reduction. In an effort to overcome many of these potential biases and better estimate the magnitude of femur length shortening in fetuses with Down syndrome, a retrospective review of femur length differences between 16 Down syndrome and 194 control fetuses was carried out. All scans were performed by one examiner who used the same equipment and measurement technique. A significant reduction in the observed to expected femur length ratio for a given biparietal diameter was identified in the Down versus control fetuses (0.9574 95% confidence interval 0.9197, 0.9952 versus 0.9999 95% confidence interval 0.9913, 1.0086) (p less than 0.008). However, the magnitude of this reduction was not sufficient to permit the use of this sonographic approach as an isolated marker for fetal Down syndrome.

Biometry↗

PubMed1989

The prevalence and biologic significance of lupus anticoagulant and anticardiolipin antibodies in a general obstetric population.

Circulating antibodies to negatively-charged phospholipids have been implicated in the genesis of adverse pregnancy outcomes. However, it has yet to be established that these antibodies are causative or that they are invariably associated with untoward perinatal outcomes. To address this issue, the prevalence of lupus anticoagulant and anticardiolipin antibodies was recorded in a low-risk obstetric population, and the outcome of untreated pregnancies were evaluated. Two of 737 patients (0.27%) had lupus anticoagulant documented by a prolonged activated partial thromboplastin time that did not correct this mixing studies. In comparison, greatly elevated concentrations of immunoglobulin M-anticardiolipin antibodies or immunoglobulin G-anticardiolipin antibodies were identified in 16/737 (2.2%) patients by means of an enzyme-linked immunosorbent assay. Spontaneous abortions occurred in both lupus anticoagulant-positive patients, suggesting that the activated partial thromboplastin time used was a relatively insensitive but specific marker for antiphospholipid antibody-associated adverse pregnancy outcomes. In contrast, although 12 of 16 anticardiolipin antibodies-positive pregnancies were complicated by perinatal loss, preterm delivery, or fetal growth retardation, four patients had uncomplicated pregnancies. Moreover, the distribution of anticardiolipin antibodies concentrations in these four patients was not clustered among the lowest anticardiolipin antibodies values, and anticardiolipin antibodies concentrations correlated weakly with adverse outcomes. These findings suggest that antiphospholipid antibodies are related to adverse pregnancy outcomes in a complex fashion and that therapy is not always required for acceptable outcomes in patients without other risk factors.

Adult↗

PubMed1989

Clinical significance, prevalence, and natural history of thrombocytopenia in pregnancy-induced hypertension.

The purpose of this study was to establish the prevalence and clinical significance of thrombocytopenia in pregnancy-induced hypertension (PIH). Thrombocytopenia, defined as a platelet count less than 100,000/mm3 was found in 11.6% of all patients with PIH. Logistic regression analysis was used to assess the relative contribution of thrombocytopenia, proteinuria, and the degree of hypertension to maternal and perinatal outcome. Thrombocytopenia was the principal contributor to the occurrence of abdominal pain, liver dysfunction, the presence of schistocytes in the peripheral smear, proteinuria, fetal distress, and the requirement for blood transfusions. Thrombocytopenia was also associated with a higher incidence of preterm delivery and intrauterine growth retardation. The nadir platelet count occurred within 48 hours of delivery in 56.7% (21 of 37) of cases. The median number of days for recovery of the thrombocytopenia was 2.0 days (range, 0 to 8 days). In five patients thrombocytopenia preceded the clinical manifestations of PIH. We conclude that thrombocytopenia is an independent and important risk factor for the occurrence of maternal and perinatal complications in PIH.

Abdomen↗

PubMed1988

Amniotic fluid alpha-fetoprotein concentrations in twin gestations: dependence on placental membrane anatomy.

Placental membrane anatomy was evaluated after delivery in 65 twin pregnancies undergoing genetic amniocentesis with amniotic fluid alpha-fetoprotein and acetylcholinesterase determinations when indicated. Each twin member in the 57 uncomplicated twin pregnancies was found to have an amniotic fluid alpha-fetoprotein concentration similar to that of singleton pregnancies of an equivalent gestational age. Eight twin pregnancies were found to be discordant for fetal anomalies associated with an elevated amniotic fluid alpha-fetoprotein and acetylcholinesterase level. The amniotic fluid alpha-fetoprotein concentration in the unaffected fetus in these eight cases was found to be dependent on placental membrane structure. Of the five discordant twin pregnancies with diamnionic-dichorionic placentas, all unaffected twins demonstrated an amniotic fluid alpha-fetoprotein concentration within the normal range for gestational age with a normal acetylcholinesterase level. In three twin pairs with diamnionic-monochorionic placentas, the unaffected twin member had significantly elevated amniotic fluid alpha-fetoprotein and acetylcholinesterase levels, which suggested diffusion of alpha-fetoprotein and acetylcholinesterase through the amnion-amnion interface.

Acetylcholinesterase↗