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Biomedical subjects

R K Silver

Publications and source records attributed to R K Silver.

At least 55 records · Page 3Linked to original sources

Soluble factors produced by isolated first-trimester chorionic villi directly inhibit proliferation of T cells.

Supernatants from human trophoblast cultures have been reported to be both suppressive and stimulatory of mitogen-induced T-lymphocyte transformation. These discordant observations have been attributed to methodologic differences among laboratories, but may instead relate to inadvertant cellular contamination during long-term culture. Retrieval of chorionic villi for genetic analysis has provided an opportunity to evaluate the immunoregulatory activity of the isolated villus preparation, unencumbered by extended culture techniques. Primary cytotrophoblast cultures were established from karyotypically and clinically normal pregnancies and the supernatants were recovered. Allogenic mononuclear cells, stimulated by phytohemagglutinin, were uniformly inhibited by trophoblast supernatant (mean inhibition, 34.3%). This inhibition was verified in one-way, mixed lymphocyte cultures and suppression of T cells occurred in a dose-dependent fashion over a range of trophoblast supernatant concentrations. No evidence of suppressor T-cell induction by trophoblast supernatant was noted with the use of both phenotypic studies of lymphocytes incubated with trophoblast supernatant and a functional suppressor T-cell inducer assay. We believe that the immunoregulatory properties of trophoblast supernatants identified with the use of these methods more closely approximate the paracrine function of the in situ villus.

Analysis of Variance↗

An evaluation of the chorionic villus sampling learning curve.

Prior studies have identified a correlation between the rate of fetal loss (subsequent to chorionic villus sampling) and the operator's level of experience. However, centers performing only modest numbers of procedures during the initial phase of their programs have reported loss rates similar to those of the more active diagnostic units. Our personal experience would suggest that a "learning curve" for chorionic villus sampling does exist but that fetal loss may be an insensitive end point with which to evaluate the impact of cumulative performance. In an attempt to quantify the learning curve that we have appreciated subjectively, a detailed analysis of our initial experience with chorionic villus sampling was undertaken. Between May 1988 and August 1989, a total of 185 procedures were accomplished consecutively by one operator and form the basis for this analysis. Transcervical (n = 82) and transabdominal (n = 103) techniques were used for posterior and anterior-fundal placental locations, respectively. Three pregnancy losses occurred and insufficient material for analysis was retrieved in five patients. We observed a significant reduction in the required number of placental aspirations during the study interval (p less than 0.001). When analyzed separately, consecutive performances of the transabdominal technique demonstrated a significant reduction in the mean number of placental passes (p less than 0.00001) along with more efficient sampling (increased sample weight/aspiration attempt; p less than 0.01). Although the fetal loss rate is a critical measure of safety and may directly be related to operator experience, other measures of expertise (e.g., single-pass success rate) may be more appropriate indicators of competence and may be useful to centers wishing to initiate their own chorionic villus sampling programs.

Abortion, Spontaneous↗

Fetal posterior urethral valve syndrome: a prospective application of antenatal prognostic criteria.

A case of posterior urethral valve syndrome is presented. Four weeks after a normal 24-week ultrasound examination, diminished amniotic fluid, megacystis, and renal hyperechogenicity were observed. A repeat ultrasound examination at 30 weeks' gestation identified oligohydramnios and increased renal echogenicity. These findings prompted the performance of a percutaneous cystocentesis to assess fetal renal function indirectly. The specimen was evaluated for osmolality and sodium and chloride concentrations. The urine electrolyte concentrations (sodium 115 mEq/L; chloride 93 mEq/L) and the osmolality (230 mOsm/L) were elevated, suggesting impaired renal function and a poor prognosis. Despite these findings, aggressive management was used, including administration of antenatal corticosteroids and elective preterm delivery. A percutaneous cystocentesis was required during the infant's initial resuscitation, followed by a difficult urethral catheterization. Ultimately, a vesicostomy performed on day 4 of life was associated with prompt return of renal function (serum creatinine 0.7 mg/dL at the time of discharge). At 6 months of age, normal renal function has been documented and the vesicostomy has been closed. This case demonstrates the potential limitations of available prognostic criteria in evaluating fetal urinary obstruction and residual renal function. In selected cases (when the onset of obstruction is documented in the third trimester), refinement of these prognostic criteria may be indicated. Similar cases may be best managed by preterm delivery and prompt postnatal decompression.

Adult↗

Initiating a chorionic villus sampling program. Relying on placental location as the primary determinant of the sampling route.

In initiating a chorionic villus sampling (CVS) protocol, we relied upon placental locations as the determinant in the choice of technique. An anterior or fundal location prompted a transabdominal (TA) CVS, while the transcervical (TC) approach was reserved for posterior placentas. A coaxial needle system was used for TA CVS (18-gauge, 15-cm guide needle and 20-gauge, 20-cm sampling needle), while TC CVS was accomplished with a 5.8-French, 27-cm polyethylene catheter. Between July 1988 and February 1989 our initial 118 procedures were performed for 115 consecutive pregnancies using this protocol. Testing indications and antenatal characteristics of the TA (n = 56) and TC (n = 63) groups were similar. One procedure failure occurred in the TC group, and a single aspiration was sufficient in 59% of the cases (TA, 30/55; TC, 39/63). In TC procedures an increased aggregate sample weight was observed as compared to TA cases (25.8 g vs. 16.9 g, respectively; P less than .001). This difference was not attributable to an increased number of placental aspirations in TC cases. One abnormal karyotype was observed (45X), and four pregnancy losses occurred (TC, 3; TA, 1). Using placental location to determine the choice of CVS technique appears to be feasible and may be associated with a lower failure rate during a facility's initial experience (when compared to reliance upon one technique alone). Trials comparing the safety of these two methods should consider placental location an independent variable before randomization.

Abdomen↗

Impact of antenatal dexamethasone administration on respiratory distress syndrome in surfactant-treated infants.

Neonatal lung disease is primarily responsible for the perinatal morbidity and mortality associated with preterm birth. Recently exogenous surfactant replacement therapy has been used to prevent or treat respiratory distress syndrome. As part of a multicenter, preventive trial between February 1986 and December 1988 using calf-lung surfactant extract, we treated 147 infants with single dose calf-lung surfactant extract. We analyzed this experience to evaluate the possibility that antenatal steroids may be additive (with calf-lung surfactant extract) in reducing both the incidence and severity of respiratory distress syndrome. Although a reduction in the incidence of respiratory distress syndrome was observed among the 33 neonates exposed to antenatal dexamethasone when compared with the 114 infants given calf-lung surfactant extract alone, the difference was not significant (37.7% vs. 24.2% p = 0.15). However, comparison of neonatal subsets previously shown to benefit most from steroid use revealed an additive effect between calf-lung surfactant extract and dexamethasone in reducing both the incidence and severity of respiratory distress syndrome. Of the 99 singleton pregnancies, only 2 of 16 infants treated with calf-lung surfactant extract and dexamethasone developed respiratory distress syndrome, compared with the 33 of 83 calf-lung surfactant extract cases (p less than 0.05). A similar reduction was observed in infants between 28 and 32 weeks' gestation (calf-lung surfactant extract, 21 of 79 vs. calf-lung surfactant extract and dexamethasone, 0 of 24; p less than 0.05). A reduction in disease severity was observed in male offspring (moderate or severe respiratory distress syndrome only; 22 of 63 vs. 2 of 22; p less than 0.05). Potential confounding variables (e.g., gestational age at birth, birth weight, exposure to tocolytics before delivery, fetal pH at birth) were similar in all comparisons. We conclude that an additive effect between dexamethasone and calf-lung surfactant extract is observed in selected cases. It may therefore be appropriate to maximize antenatal steroid use in centers where exogenous surfactant is available.

Acid-Base Equilibrium↗

Impact of residual amniotic fluid volume in patients receiving parenteral tocolysis after premature rupture of the membranes.

The inhibition of labor subsequent to premature rupture of the membranes remains controversial. To evaluate the possibility that diminished amniotic fluid volume impacts on the latent period in patients receiving tocolytic therapy after premature rupture of the membranes, we reviewed our recent clinical experience with premature rupture of the membranes and the use of tocolytic agents. Between January 1985 and June 1988, 70 singleton pregnancies with premature rupture of the membranes between 25 and 34 weeks of gestation without prior tocolytic therapy were included. Ritodrine (n = 22), magnesium sulfate (n = 37), or both agents (n = 11) were administered and followed by oral terbutaline if tocolysis was achieved. Ultrasonographic examination was performed after admission and patients were grouped on the basis of estimates of residual amniotic fluid volume. Fourteen patients had adequate fluid volume; 20 had diminished fluid volume, and 36 had oligohydramnios. Patients with adequate fluid volume had a significantly longer interval between tocolytic therapy and delivery when compared with the other two categories (analysis of variance, p less than 0.001), and proportionately more patients remained undelivered for greater than 1 week (adequate 8 of 14 vs. diminished 3 of 20 and oligohydramnios 3 of 36; p less than 0.001). In the 18 patients with premature rupture of the membranes before 30 weeks' gestation, adequate fluid volume was associated with the longest latent period (adequate 14.0 days; diminished 12.6 days, and oligohydramnios 2.8 days; analysis of variance, p less than 0.05). We conclude that tocolytic therapy is of little benefit in the presence of oligohydramnios. If additional prospective studies of tocolytic efficacy in pregnancies complicated by premature rupture of the membranes are undertaken, inclusion of residual amniotic fluid volume as an independent variable before randomization should be considered.

Amniotic Fluid↗

Prediction of hematocrit decline after intravascular fetal transfusion.

Fetal blood sampling and intravascular transfusion via cordocentesis allow more precise fetal evaluation and treatment in isoimmunized pregnancies. However, the timing of repeat transfusion has remained empiric. In this report we review our experience with fetal transfusions in isoimmunized pregnancies to evaluate the ability to predict fetal hematocrit decline and thereby determine the optimum timing for repeat transfusions. Between March 1986 and March 1988, 60 intravascular fetal transfusions were performed in 20 patients. Fetal transfusions were excluded from analysis if blood samples were unable to be obtained before and after transfusion, as well as at the beginning of the next transfusion or birth. Fifty-three procedures were analyzed. Two equations were used to predict the fetal hematocrit at the subsequent transfusion. The difference between observed and predicted hematocrits at the beginning of a subsequent transfusion or birth was -0.9% +/- 5.8% with equation 2, which was the more accurate formula in the majority of fetuses. Prediction of fetal hematocrit decline may be used to determine the optimum timing of repeat transfusion.

Blood Transfusion, Intrauterine↗

Perinatal management of meconium staining of the amniotic fluid.

The pathogenesis of meconium passage and the pathophysiology of meconium aspiration are reviewed. Intrapartum and neonatal strategies for the prevention of meconium aspiration syndrome are presented in historical perspective, and newer interventions are appraised.

Amniotic Fluid↗

The perinatal management of central nervous system anomalies.

The diagnosis, proper evaluation, and treatment of a CNS anomaly requires the participation of many subspecialists and support personnel. The outcome can be favorably modified through the choice of elective termination, aggressive or passive perinatal intervention, and the 24-hour availability of neurosurgical expertise. At the conclusion of the pregnancy, accurate and informative counseling also should be provided. Although these discussions need not take place immediately, review of the final diagnosis, its risk of recurrence, and the appropriate screening for subsequent pregnancy should be included.

Central Nervous System↗

Fetal acidosis in prolonged pregnancy cannot be attributed to cord compression alone.

Fetal heart rate abnormalities associated with prolonged pregnancy have been attributed to umbilical cord vulnerability rather than placental insufficiency. Although intrapartum fetal heart rate patterns indicative of umbilical cord compression are common beyond 41 weeks' gestation, fetal intolerance to labor develops only in a subset of such patients. To test the hypothesis that suboptimal placental function contributes to reduced amniotic fluid volume and, ultimately, to fetal intolerance to labor, we prospectively collected biochemical and clinical data on 112 prolonged pregnancies. Data analysis was blinded to outcome and included cord blood acid-base measurements and intrapartum fetal heart rate interpretation. We observed a high incidence of umbilical cord compression (46.4%), but this finding was not predictive of emergent delivery in 32 of 52 cases (61.5%). Fetal acidosis (arterial pH less than 7.20) occurred more often in patients with cord compression, but the anticipated increase in carbon dioxide tension was not observed. Instead, a primary metabolic or combined acidosis was encountered in those fetuses delivered emergently. The additional findings of lower amniotic fluid volume and diminished birth weight in those patients delivered for fetal intolerance to labor suggest a direct role for suboptimal placental function in selected patients with prolonged pregnancy.

Acidosis↗

Predictors of vaginal delivery in patients with a previous cesarean section, who require oxytocin.

Prospective analysis of 98 consecutive patients at term pregnancy with one previous cesarean section, who received oxytocin during a trial of labor (34 inductions, 64 augmentations), was undertaken to identify specific factors associated with successful vaginal delivery. The overall vaginal delivery rate was 59.2%. Comparing route of delivery in the induction and augmentation groups separately revealed no significant differences in maternal height, weight, or parity, duration of membrane rupture, length of oxytocin treatment or maximum dose, cervical examination on admission or before oxytocin treatment, or use of conduction anesthesia. A previous vaginal delivery favored repeat vaginal delivery in patients with augmentation while a nonrecurrent indication was significantly associated with vaginal delivery in all patients. After the beginning of oxytocin augmentation, the cervical dilatation rate was 1.82 cm/hr in patients delivered vaginally, compared with 0.18 cm/hr in those requiring cesarean section (p less than 0.001). Any cervical dilatation during the first 2 hours of augmentation was associated with more frequent vaginal delivery: 24 of 40 vaginal deliveries (60%) versus six of 24 cesarean sections (25%, p less than 0.01). Discriminant analysis correctly identified route of delivery in 85.3% of those with induction and 87.5% of patients with augmentation. During a trial of labor, oxytocin induction or augmentation is effective in a majority of patients. Furthermore, an early response during augmentation is of predictive value when such patients are being managed.

Cervix Uteri↗

Umbilical cord size and amniotic fluid volume in prolonged pregnancy.

Expectant management of prolonged pregnancy is predicated on reassuring biophysical testing. However, even the combination of a reactive nonstress test and normal amniotic fluid volume may not prevent subsequent morbidity. To test the hypothesis that diminished cord Wharton's jelly incurs risk of peripartum cord compression in addition to decreased amniotic fluid, 68 patients with confirmed gestational age greater than or equal to 41 weeks were evaluated prospectively with semiweekly nonstress tests and weekly ultrasound examinations. Amniotic fluid volume was assessed, and umbilical cord diameter was measured and then correlated with the quantity of Wharton's jelly at delivery, determined by cord circumference. A significant correlation between cord circumference and umbilical cord diameter was observed, even in those patients with decreased amniotic fluid volume. Either an amniotic fluid volume less than 3.8 cm or an umbilical cord diameter less than 1.6 cm was associated with significant cord compression patterns. Peripartum morbidity was greatest in the presence of a smaller cord and decreased fluid, suggesting a synergism between these two factors for the risk of cord compression in prolonged pregnancy.

Amniotic Fluid↗

When does a statistical fact become an ethical imperative?

Trial of labor is a safe and effective management alternative but remains underused in current clinical practice. To explore whether this underuse is justified, decision analysis is developed to compare a trial of labor with elective repeat cesarean section. With the use of available probability estimates and outcome scoring based on a survey of perinatologists, decision analysis identifies trial of labor as superior to elective repeat cesarean section for both the mother and the neonate. Going beyond the simple comparisons of management options and outcomes, the ethical implications of such results are discussed in terms of "utility ethics," "informed consent," and "universal equality." Such considerations suggest that there is a professional (ethical) responsibility to increase the application of trial of labor.

Cesarean Section↗

Intrapartum management of the fetus with idiopathic hydrocephalus.

Intrapartum management of fetal idiopathic hydrocephalus (IH) diagnosed late in pregnancy is controversial. Normal intellectual development is possible in many of these infants when neurosurgical intervention is undertaken in the neonatal period. Aggressive intrapartum management is indicated in most of these cases regardless of cortical mantle thickness. However, routine abdominal delivery is associated with increased maternal morbidity without proven fetal benefit. Transvaginal cephalocentesis for fetuses with IH in the cephalic presentation, followed by spontaneous vaginal delivery, lessens maternal morbidity and is compatible with good neonatal outcome.

Adolescent↗

Effect of amniotic fluid bacteria on the course of labor in nulliparous women at term.

Patients with intraamniotic infection have an increased rate of cesarean delivery. To determine whether bacterial colonization of amniotic fluid affects uterine activity or delivery outcome, serial amniotic fluid samples were collected from 41 nulliparous patients in active labor with ruptured membranes for longer than 12 hours. To define positive changes, these samples were divided arbitrarily by colony count change using an increase of less than 10(2) colony-forming units per milliliter; greater than or equal to 10(2) but less than 10(4) colony forming units per milliliter; or greater than or equal to 10(4) colony forming units per milliliter. Nineteen, seven, and 15 sample sets fulfilled these criteria, respectively. Comparing serial samples with these changes in colony count revealed no significant difference in ten labor and delivery variables. Based on virulence of the isolates identified, samples were then divided into high (N = 19) or low (N = 16) virulence in both samples. Compared with sample sets with persistently low-virulence organisms, sample sets with persistently high-virulence isolates had a lower cervical dilatation rate (0.49 +/- 0.39 versus 0.98 +/- 0.58 cm/hour, P = .04), despite an increased maximum oxytocin dose (10.0 +/- 8.0 versus 5.4 +/- 5.2 mU/minute, P = .03). Controlling for birth weight, labor length, and epidural, magnesium sulfate, and oxytocin use, it was found that patients with high-virulence bacteria also had a higher cesarean section rate (57.9 versus 25.0%, P = .05). These results support a causal relationship between high-virulence bacteria in the amniotic fluid and poor cervical dilatation response to oxytocin in patients at risk for the development of intrapartum infection.

Amniotic Fluid↗