Biomedical subjects

R K Silver

Publications and source records attributed to R K Silver.

At least 37 records · Page 2Linked to original sources

PubMed1995

Midtrimester Rh sensitization associated with circulating anticardiolipin antibodies and elevated maternal serum alpha-fetoprotein. A case report.

The incidence of antepartum Rh isoimmunization has been limited by third-trimester Rh immune globulin (RhIg) administration. Prophylactic failures are uncommon but can occur if sensitization takes place prior to the 28th week of gestation. We report a case of midtrimester Rh sensitization in an anticardiolipin antibody-positive primipara coincident with the discovery of an elevated maternal serum alpha-fetoprotein value, oligohydramnios and fetal growth retardation. This case suggests that fetal-maternal hemorrhage and subsequent sensitization may be facilitated by anticardiolipin antibody-induced placental damage. Prophylactic midtrimester RhIg administration might avoid sensitization in similar cases.

Adult↗

PubMed1995

Understanding prostaglandin metabolites and platelet-activating factor in the pathophysiology and treatment of the antiphospholipid syndrome.

As clinicians include an immunologic evaluation in their assessment of recurrent fetal loss among otherwise asymptomatic women, the diagnosis of PAPS will be uncovered with greater frequency. Our understanding of the underlying pathophysiology of PAPS is critical if we are to propose safe and rational therapies for these patients. It appears as though prostaglandin metabolites are implicated directly in the processes that culminate in this unique, localized vasculopathy; and research is actively progressing with this focus in mind. For the present, we should look critically at the available treatments to be sure that the rationale for use is consistent with current evidence and that the margin of fetal and maternal safety justifies their use. To date, only low-dose aspirin appears to alter prostaglandin metabolites favorably and is thus, emerging as our safest and most efficacious treatment.

Abortion, Habitual↗

PubMed1994

Congenital malformations subsequent to chorionic villus sampling: outcome analysis of 1048 consecutive procedures.

We wished to identify the types and frequencies of malformations among continuing pregnancies exposed to chorionic villus sampling (CVS) and to determine whether selected procedure-related variables differ between the normal and anomalous cohorts. CVS was performed in 1048 patients between May 1988 and January 1992. Prospective assessment of perinatal outcome was ascertained by (1) physician-patient phone contact within 1 week of sampling, (2) ultrasound evaluation of the fetal anatomy at mid-gestation, (3) a detailed post-partum questionnaire completed by the referring obstetrician, and (4) a telephone interview with each patient after the expected date of confinement. Twenty-seven major malformations were documented among 938 pregnancies (live born, n = 934; electively terminated, n = 4), and included cardiac malformations (5), hypospadias (5), craniosynostosis (2), pyloric stenosis (2), inguinal hernia (2), polydactyly (2), syndactyly, distal extremely hemimelia, anencephaly, hydrocephalus, cleft lip and palate, omphalocele, diaphragmatic hernia, thanatophoric dysplasia, and unilateral cataract. Normal and anomalous cohorts were similar with respect to sampling method (transabdominal/transcervical ratio), mean gestational age at CVS, single-pass success rate, and mean total sample weight. No relationship between any procedure-related variable and the risk of malformation was observed.

Chorionic Villi Sampling↗

PubMed1994

Endothelial cell 1-acyl-platelet-activating factor synthesis in response to anticardiolipin antibody-positive serum fractions.

Enhanced endothelial cell 1-acyl platelet-activating factor (1-acylPAF) synthesis has been identified as a consequence of anticardiolipin-antibody-positive serum exposure. While this observation suggests that PAF analogues may play a role in antibody-mediated vasculopathy, it has not been determined whether the antibodies themselves are directly responsible for stimulating 1-acylPAF production. The objective of the current study was to determine whether extracted immunoglobulins or non-immunoglobulin serum constituents are responsible for the increased endothelial cell 1-acylPAF production previously observed. Sera from six ACA-positive, non-pregnant women were precipitated with ammonium sulfate and dialyzed to extract their respective immunoglobulin fractions. IgG, A and M concentrations were measured by nephelometry before and after precipitation and enzyme immunoassay was used to quantify anticardiolipin antibody activity in both whole serum and immunoglobulin suspensions. Paired endothelial cell monolayers were incubated separately with 20% whole serum and the corresponding immunoglobulin fraction from each patient source. After ionophore A23187 stimulation, intracellular PAF production was measured by lipid extraction and radiolabeling. RadylPAF species were distinguished by zonal thin-layer chromatography. Mean radylPAF synthesis was compared between experimental conditions by paired T-test. Significantly more endothelial cell radylPAF synthesis was observed subsequent to whole serum exposure as compared to incubation with the corresponding immunoglobulin fractions (19154 +/- 1916 vs 11785 +/- 1778; dpm, mean +/- SE; p = 0.007); the majority of recovered radylPAF was the sn-1-acyl derivative. Serum samples recovered after immunoglobulin extraction, retained similar stimulatory activity for radylPAF (23045 +/- 4175 dpm) in comparison to intact whole serum (19635 +/- 1266 dpm; p = 0.25). These findings suggest that in ACA-positive serum, non-immunoglobulin constituents provide greater stimulation of 1-acylPAF synthesis than the immunoglobulins themselves.

Antibodies, Anticardiolipin↗

PubMed1994

A comparison of pregnancy loss between transcervical and transabdominal chorionic villus sampling.

OBJECTIVE: To evaluate the comparative safety of transcervical and transabdominal chorionic villus sampling (CVS). METHODS: From May 1988 to January 1992, CVS was performed by two operators at 9-12 weeks' gestation in 1048 singleton pregnancies. The sampling method for each patient, transabdominal or transcervical, was chosen primarily based upon placental location; the transabdominal route was used for anterior or fundal location and the transcervical route for posterior placentation. Perinatal outcome was assessed by post-procedure patient telephone contact, mid-gestation ultrasound evaluation, postpartum questionnaire completed by the referring obstetrician, and telephone interview with each patient after delivery. RESULTS: Complete follow-up was available in 1012 cases (97%). Excluding 39 elective abortions, 35 of 973 euploid pregnancies aborted spontaneously. The difference in fetal loss rate between transcervical and transabdominal CVS approached statistical significance (5.2 versus 2.9%; P = .058). Bleeding before CVS (P = .006) and multiple placental aspirations (P = .022) were associated with fetal loss for the entire study group. An interaction between uterine position and sampling method was also indicated; an increased loss rate was associated with transcervical CVS in the presence of uterine retroversion (P = .0017). CONCLUSION: Despite choosing the preferred CVS method for each patient, an increased loss rate may be associated with transcervical sampling in the presence of uterine retroversion.

Abdomen↗

PubMed1993

Comparative trial of prednisone plus aspirin versus aspirin alone in the treatment of anticardiolipin antibody-positive obstetric patients.

OBJECTIVE: We compared the use of aspirin alone with combined therapy (prednisone plus aspirin) in antiphospholipid antibody-positive obstetric patients with prior adverse pregnancy outcome. STUDY DESIGN: Thirty-nine patients meeting specific laboratory and clinical inclusion criteria were randomized to receive either combined therapy (prednisone plus low-dose aspirin, n = 17) or aspirin alone (n = 22). The daily aspirin dose was 81 mg; prednisone was begun at 20 mg/day and increased or decreased on the basis of observed changes in serial antibody levels. Perinatal outcomes were compared between groups. Evaluation of treatment-related maternal complications and serial antibody titers was also accomplished. RESULTS: Thirty-four randomized subjects were evaluable (prednisone plus low-dose aspirin, n = 12 vs aspirin only, n = 22); no perinatal losses were observed in the study cohort. Preterm delivery was experienced by significantly more patients receiving prednisone plus low-dose aspirin than aspirin only (8/12 vs 3/22, respectively; p = 0.003), and prednisone exposure appeared to be an independent risk factor for preterm birth. CONCLUSIONS: The use of prednisone therapy in conjunction with low-dose aspirin does not appear to improve outcome and may provoke obstetric complications in antiphospholipid antibody-positive patients.

Adult↗

PubMed1993

Perinatal factors influencing survival at twenty-four weeks' gestation.

OBJECTIVE: Our objective was to identify those obstetric and neonatal factors associated with survival in infants delivered at 24 weeks' gestation. STUDY DESIGN: The obstetric and pediatric data bases from the two hospitals in our perinatal center were examined to ascertain all infants delivered between 1987 and 1989 whose gestational age was 24 weeks to 24 weeks 6 days. This time interval was chosen to coincide with the introduction of prophylactic exogenous surfactant. Data were abstracted from the maternal antepartum and intrapartum records and the neonatal records, with specific attention to objective risk factors related to survival. RESULTS: Forty-five pregnant patients were identified and delivered of 52 infants. Seventeen newborn infants survived (33%). Univariate comparisons between survivors and nonsurvivors revealed more aggressive intrapartum care in the former cohort as represented by the frequencies of internal fetal heart rate monitoring (p = 0.005), maternal oxygen therpay (p = 0.003), and maternal position change to remediate decelerations (p = 0.001). Planned exclusion of cesarean delivery was more common in those pregnancies that ended in fetal or neonatal death (29/35 vs 7/17; p = 0.006). Although a greater proportion of infants delivered by cesarean section survived (6/11 vs 11/41), this difference was not significant (p = 0.17). With the use of logistic regression, the best predictor of survival was gestational age at delivery. Neonatal care was more aggressive among survivors, as measured by the relative frequencies of resuscitation and surfactant administration. Respiratory distress syndrome was either absent (n = 6) or mild (n = 6) in a majority of the survivors, and respiratory insufficiency was the major cause of neonatal death. CONCLUSION: Perinatal outcome at 24 weeks' gestation appears most dependent on gestational age at delivery. The intensity of intrapartum care and neonatal support, as well as clinical biases regarding survivability, may also influence outcome.

Birth Weight↗

PubMed1993

Antenatal steroid therapy before 33 weeks' gestation.

OBJECTIVE: The purpose of this study was to determine those factors influencing contemporary antenatal steroid use in pregnancies delivered prior to 33 weeks of gestation. METHOD: We analyzed the clinical circumstances of 86 consecutive patients who delivered prior to 33 weeks of gestation and compared to 20 women who received dexamethasone prior to delivery with the remaining 66 untreated cases. RESULT: Known risk factors for preterm delivery (e.g. prior preterm birth, n = 17; prior admission and tocolysis during the index pregnancy, n = 15) did not discriminate between treated and untreated subsets. Premature membrane rupture (3/20 vs. 34/66; P < 0.01) and documented preterm labor (1/20 vs. 23/66 P < 0.01) were more common in the untreated cohort and a shorter mean interval from admission to delivery was also observed (2.8 vs 11.2 days). However, a full course of steroids would have been possible in 22/66 untreated women, since delivery was delayed for at least 36 h in these patients. CONCLUSION: These observations reflect the fact that many preterm births cannot be anticipated, even among hospitalized patients. We would therefore suggest that universal steroid treatment be considered for all women with documented preterm labor prior to 33 weeks of gestation. Initiation of steroid therapy at the referral center, (prior to maternal transport) should also be considered. Since both premature membrane rupture and early gestational age (24-28 weeks') confounded many of these cases, steroid use in patients with these circumstances should be reevaluated.

Cohort Studies↗

PubMed1993

Acetylsalicylic acid inhibits anticardiolipin antibody-induced platelet-activating factor (PAF) synthesis.

Enhanced endothelial cell PAF synthesis has been identified as a consequence of anticardiolipin antibody (ACA)-positive serum exposure. We proposed this observation as a contributing factor to thrombogenesis in women with the antiphospholipid syndrome. Since acetylsalicylic acid (ASA) is an accepted therapeutic alternative in these patients, we sought to determine if ASA would attenuate endothelial cell PAF production resulting from ACA exposure. Using primary, confluent monolayers of umbilical vein endothelial cells, experiments were performed to evaluate PAF synthesis after incubation with antibody-positive serum and ASA. Total PAF and its radyl-derivatives (1-alkyl- and 1-acyl-PAF) were quantified by tritiated acetate incorporation, phospholipid extraction, thin-layer chromatography and scintillation spectroscopy. ASA consistently decreased ACA-induced PAF synthesis (No ASA, 9573 +/- 443 vs 1mmol/L ASA, 4829 +/- 838 dpm/ml; p = 0.016) and the observed reduction was dose-dependent over a range of ASA concentrations (0.1, 1, 10 and 100 mmol/L; ANOVA, p = .00015). Reduced PAF synthesis was also observed in cultures exposed to ASA and incubated with antibody-negative serum. These observations suggest that in ACA-positive women, the antithrombotic effects of ASA may relate in part, to reduced endothelial cell PAF synthesis.

Antibodies, Anticardiolipin↗

PubMed1992

Factors associated with multiple-pass procedures during chorionic villus sampling: a video analysis.

Multiple placental passes during chorionic villus sampling (CVS) increase the risk of fetal loss; however, specific factors that predispose to repeat aspiration have not been delineated. To identify anatomic and technical variables associated with multiple-pass procedures, a detailed review of 205 videotaped CVS procedures (single pass = 163; multiple pass = 42) was performed, blinded to pregnancy outcome. The route of sampling did not influence the need for multiple aspiration attempts (transabdominal--30/135; transcervical--12/70), nor was placental location alone discriminatory. However, the combination of a posterior placenta and uterine retroversion was observed more frequently in the multiple-pass cohort (8/42 vs. 9/163; p less than 0.05). In transabdominal cases, suboptimal needle placement (e.g., perpendicular to the placental long axis) was more common in the initial aspiration of a multiple-pass procedure (21/30 vs. 38/105; p less than 0.01), while limited penetration of the catheter tip (e.g., just inside the placental edge) characterized a majority of multiple-pass cases in the transcervical subset (7/12 vs. 3/58; p less than 0.0001). A case-control cohort was constructed to evaluate the impact of these technical variables on sampling efficacy, independent of the influence of uterine position and placental site. In that analysis, suboptimal location and/or orientation of the sampling device remained characteristic of multiple-pass cases. We conclude that further reduction in the frequency of multiple-pass procedures might be achieved by consistent placement of the device tip in the central placental mass. Unlike amniocentesis, where any point of amnion entry will suffice, this technical nuance should be emphasized with CVS to maximize the single-pass success rate.

Case-Control Studies↗

PubMed1992

Interlaboratory variation in antiphospholipid antibody testing.

OBJECTIVE: Because of the widespread use of antiphospholipid antibody testing in the evaluation of patients with recurrent pregnancy loss, we evaluated the consistency of results among laboratories testing for anticardiolipin antibody and the lupus anticoagulant. STUDY DESIGN: A questionnaire regarding methods used and samples of blood from 20 patients were sent to five university-based and five commercial facilities for antiphospholipid antibody testing. RESULTS: The responses of the participating laboratories to the questionnaires revealed significant differences in methods, standardization, and units of reporting. For anticardiolipin antibody, the number of specimens found to be positive for any isotype (immunoglobulin G, M, or A) varied considerably among laboratories, with a range of 5 to 13. All laboratories were in agreement (i.e., at least one isotype was present or all were absent) for only 5 of 20 specimens (25%). In contrast, lupus anticoagulant results were more reproducible, although one facility reported results markedly discordant from the other four laboratories. CONCLUSION: These observations suggest that significant interlaboratory variation exists in antiphospholipid antibody, and particularly anticardiolipin antibody, testing and might lead to unnecessary therapeutic interventions.

Antibodies↗

PubMed1992

Amniotic fluid platelet-activating factor (PAF) is elevated in patients with tocolytic failure and preterm delivery.

Certain biological properties of PAF, including its ability to promote PGE2 synthesis and to induce myometrial contractions, support its potential role in parturition. The presence of PAF in amniotic fluid of human pregnancy appears to correlate with normal and pathologic labor. To further refine this relationship, we selected the clinical endpoints of preterm labor, tocolytic failure and preterm delivery, and evaluated amniotic fluid PAF within these groups of patients. We also measured acetylhydrolase (AH), PAF's primary degradative enzyme, to identify any correlation with the observed PAF levels. 39 specimens were collected by amniocentesis: 17 for karyotype, 6 to assess lung maturity at term and 16 in cases of preterm labor; 8 each with intact membranes and ruptured membranes at the time of sampling. PAF and AH were measured by a 3H-serotonin release bioassay and an in vitro enzyme assay using radiolabelled substrate, respectively. A 12-fold increase in PAF was found in the 3 preterm labor patients in whom tocolysis failed (delivery less than 48 hrs after treatment) compared to the 7 patients in whom labor was arrested (mean PAF = 35.0 vs 2.9 ng/ml, respectively; p = .017). Four of 8 patients with membrane rupture had preterm deliveries; their PAF levels were also elevated when compared to those that delivered at term (mean PAF = 19.7 vs 4.95 ng/ml). The 2 patients with positive amniotic fluid gram stains had the highest PAF levels in the entire cohort (30.5, 44.1 ng/ml), with low or undetectable AH. These data suggest that increased PAF production may be associated with preterm labor subsequent to tocolytic failure.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

PubMed1992

Fetal stroke associated with elevated maternal anticardiolipin antibodies.

Middle cerebral artery infarction explains some cases of congenital hemiparesis with or without neonatal stroke. The etiology of the stroke is often obscure. We describe two infants with imaging evidence of middle cerebral artery infarction whose mothers had elevated anticardiolipin antibody levels after delivery. We speculate that these antibodies may have been responsible for intrauterine thromboembolic stroke.

Adult↗

PubMed1991

Anticardiolipin antibody-positive serum enhances endothelial cell platelet-activating factor production.

Circulating antiphospholipids have been linked to recurrent pregnancy loss by a mechanism involving placental and decidual thrombosis. We hypothesized that platelet-activating factor, an autacoid synthesized by vascular endothelium, might mediate this phenomenon through its ability to promote platelet aggregation and fibrin deposition. Alternatively, antiphospholipid antibodies might exert a procoagulant effect by inhibiting the synthesis of prostacyclin. To evaluate these theories, endothelial cells (harvested from human umbilical veins) were grown to confluence and incubated for 48 hours with 20% concentrations of anticardiolipin antibody-positive and -negative human sera as well as fetal bovine serum. After incubation culture wells were stimulated with 10 mumol/ml calcium ionophore A23187 (an agonist of platelet-activating factor and prostacyclin synthesis). Intracellular platelet-activating factor was measured by tritiated acetate incorporation, phospholipid extraction, thin-layer chromatography, and scintillation spectrophotometry. Enhanced platelet-activating factor synthesis was identified in cultures incubated with anticardiolipin antibody-positive serum (25,544 +/- 2604 disintegrations per minute, mean +/- SD) when compared with anticardiolipin antibody-negative serum (18,600 +/- 3316 dpm) or fetal bovine serum (19,014 +/- 4233 dpm; analysis of variance, p = 0.033). In similar experiments, prostacyclin synthesis was determined by measuring its primary metabolite, 6-keto-prostaglandin F1 alpha, in culture supernatants. No differences between anticardiolipin antibody-positive and control cultures were observed (analysis of variance, p = 0.90). We conclude that in this endothelial cell model, anticardiolipin antibody-positive serum enhances ionophore-mediated platelet-activating factor synthesis but has no apparent effect on the production of prostacyclin. These findings suggest a potential role for platelet-activating factor in anticardiolipin antibody-mediated vascular thrombosis.

6-Ketoprostaglandin F1 alpha↗

PubMed1991

Enhanced sensitization after cordocentesis in a rhesus-isoimmunized pregnancy.

It has been suggested that the optical density at 450 nm may be an unreliable predictor of the severity of fetal anemia in the midtrimester of pregnancy; therefore fetal blood sampling, rather than amniotic fluid evaluation, should be performed in all isoimmunized pregnancies with elevated maternal antibody titers in the midtrimester. Potential complications of such an approach are discussed and an alternative plan of management is offered.

Adult↗

PubMed1991

Perinatal outcome following intravascular transfusion in severely isoimmunized fetuses.

Twenty-six severely isoimmunized pregnancies managed exclusively with ultrasonographically guided intravascular fetal transfusions are reported. The mean gestational age plus and minus one standard deviation (+/- SD) was 26.3 +/- 3.6 weeks and the mean hematocrit (+/- SD) prior to initial transfusion was 20.6 +/- 6.7%. Four of seven hydropic fetuses and 9 of 19 without hydrops were less than or equal to 26 weeks gestation at the first transfusion. Overall survival was 85% (22/26). Survival was similar whether or not fetal hydrops was present (6/7 vs. 16/19) and whether or not the first transfusion was administered at less than or equal to 26 weeks gestation (10/13 vs. 12/13).

Blood Transfusion, Intrauterine↗

PubMed1991

A prospective, randomized evaluation of intrapartum amnioinfusion. Fetal acid-base status and cesarean delivery.

Pregnancies with decreased amniotic fluid volume are prediposed to umbilical cord compression and variable fetal heart rate declerations. Intrapartum amnioinfusion has been utilized in an effort to reduce cord compression. Previous studies suggested that amnioinfusion may improve the fetal metabolic state and reduce the incidence of cesarean delivery in selected patients. In this study the hypothesis was tested that intrapartum amnioinfusion will relieve cord compression in pregnancies complicated by oligohydramnios and will result in a reduced incidence of fetal intolerance to labor as well as improved fetal acid-base status at delivery. Thirty-five patients fulfilling the inclusion criteria were randomized to either the control (n = 16) or amnioinfusion treatment group (n = 19). Analysis of the data suggested that the two groups were similar for the perinatal parameters evaluated. No differences were observed in the umbilical artery blood gas analysis or incidence of cesarean section between the two groups. Intrapartum amnioinfusion does not appear to improve the perinatal outcome in pregnancies with oligohydramnios.

Adult↗

PubMed1991

Percutaneous transvesical chorionic villus sampling: an alternative approach to the retroverted uterus.

In 458 consecutive chorionic villus sampling (CVS) procedures, we observed a significant influence of uterine position upon sampling efficacy. Compared with anteverted (N = 243) or axial (N = 149) locations, the retroverted uterus (N = 66) was associated with a lower mean sample weight per aspiration (22, 18, and 15 mg, respectively; P less than .01) and a greater frequency of multiple-pass procedures (23, 31, and 52%, respectively; P less than .0001). To improve sampling efficiency in selected cases of uterine retroversion, we adopted a transvesical approach. When compared with transabdominal or transcervical techniques, transvesical CVS had the highest single-pass success rate (33, 33, and 60%, respectively). Only one in 30 transvesical cases required three placental passes, compared with nine of 36 retroverted uteri sampled by either transabdominal or transcervical techniques (P less than .05). The mean transvesical sample weight was 18.7 mg; at least 10 mg was retrieved in all cases. Post-procedure bleeding occurred in four instances and an additional patient suffered a spontaneous loss at 16 weeks' gestation. Aneuploidy was found in four of 30 biopsy specimens, and the remaining pregnancies either have delivered at term (N = 18) or are continuing (N = 7). Our preliminary experience suggests that selected use of this CVS method may improve sampling efficiency without increasing the incidence of complications.

Analysis of Variance↗