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Biomedical subjects

W F O'Brien

Publications and source records attributed to W F O'Brien.

At least 37 records · Page 2Linked to original sources

Cerebral palsy in infants with asymmetric growth restriction.

The relationship between low ponderal index and cerebral palsy was evaluated. National Collaborative Perinatal Project and University of California Child Health and Development Study data were analyzed. Associations between low ponderal index (ponderal index < 5% for gestational age) were evaluated in the combined population, in term and preterm infants, and in non-SGA infants (with birth weights > 5% for gestational age and gender). Data from 55,571 infants, including 232 cases of cerebral palsy, were evaluated. Low ponderal index was significantly associated with CP in the delivery population (Relative risk 2.2) and in non-SGA infants (RR 1.9). Low ponderal index was a significant independent correlate of cerebral palsy (RR 1.9) in non-SGA infants after using logistic regression to correct for effects of prematurity and gender. Low ponderal index is associated with increased risk of CP, even in non-SGA infants. Assessment of the neonatal ponderal index provides an additional method of documenting prior abnormal fetal growth and development.

Birth Weight↗

The effect of maternal blood contamination on the TDx-FLM II assay.

The objective of this paper is to determine the effect of maternal blood contamination on the TDx-FLM II assay for fetal lung maturation. Thirty-one samples of amnionic fluid (AF) collected from gestations > 28 weeks were assayed for AF surfactant-to-albumin ratio using the TDx-FLM II assay. Maternal blood was added to the AF at increasing concentrations from 1:10 to 1:1280 and the TDx-FLM II was assessed on each sample. There were 7 mature (> 55), 5 transitional (40-54) and 19 immature (< 39) specimens. The addition of increasing amounts of maternal blood decreased the value of a mature and increased the value of an immature result. Six of the 7 mature values eventually became immature at high levels of contamination. No value below the mature cutoff was raised into the mature range by the addition of blood. Samples with values between 21 and 45 had a variable response to maternal blood but none were increased into the mature range. Maternal blood contamination may result in a falsely immature or borderline value, but mature results are valid regardless of the degree of contamination.

Amniocentesis↗

The effect of interleukin-1 beta and interleukin-4 on the expression of prostaglandin receptors EP1 and EP3 in amnion WISH cells.

PROBLEM: Although prostaglandin E2 (PGE2) is believed to modulate biochemical and immunological events leading to parturition, the role of prostaglandin E receptors during labor has not been investigated. METHOD OF STUDY: Amnion WISH cells were incubated in media containing increasing concentrations of either interleukin-1 beta (IL-1 beta) or IL-4. Increased EP1 and EP3 protein expression was determined by Western blot analysis with peptide-specific antibodies. Concomitant measurements of culture media PGE2 were made by an enzyme immunoassay. RESULTS: Incubation of WISH cells with IL-1 beta or IL-4 caused a two- to three-fold increase in EP1 protein levels. IL-1 beta and IL-4 also caused six- and two-fold increases, respectively, in culture fluid PGE2 concentrations. IL-1 beta or IL-4 had no effect on EP3 protein levels. CONCLUSIONS: Based on these results, it is proposed that IL-1 beta and IL-4 may be involved in the initiation and promotion of labor by inducing EP1 levels and PGE2 production in amnion.

Amnion↗

The effect of maternal blood contamination on amniotic fluid glucose and white blood cell count from preterm gestations.

OBJECTIVE: To determine the influence of maternal blood contamination on amniotic fluid (AF) glucose and white blood cell count (WBC). METHODS: Amniotic fluid from 23 preterm, nondiabetic pregnant women was studied. Maternal blood was added to the AF at increasing concentrations, and glucose and WBCs were assessed. RESULTS: The median AF glucose in the uncontaminated specimen was 43 mg/dL (range 11-86). Median glucose levels were unchanged by the addition of maternal blood until a mean +/- standard deviation AF red blood cell count of 63,000 +/- 22,000/mm3 was exceeded, at which time the median glucose level significantly increased to a median of 45 mg/dL (range 19-90). The ratio of observed to expected values of WBCs ranged from 0.12-1.8, regardless of the level of maternal blood contamination. CONCLUSION: Glucose levels in preterm AF-containing maternal blood are accurate in all except the most heavily contaminated specimens. Accurate determination of the WBC in contaminated AF is difficult.

Adult↗

Weight control in women: a challenge to the obstetrician-gynecologist.

Obesity is a major problem in American women, and there is great concern with regard to weight control among both the obese and the nonobese. Vast sums of money are spent in the area of weight reduction, often with little or no benefit. Although obesity affects longevity adversely, weight loss has not been clearly associated with a decrease in mortality risk. Reduction in weight, however, can decrease risk factors for certain diseases and improve the quality of life. Current methods of weight control include diet, exercise, surgery, and medication. Several studies have shown that, in contrast to previous supposition, medical management should be long term. Recent investigations into the basic mechanisms of appetite control, moreover, suggest that more physiologic management methods will be available in the near future.

Body Weight↗

The induction of cyclooxygenase-2 (COX-2) in intact human amnion tissue by interleukin-4.

Infection is a major cause of preterm labor. Amniotic fluid from women in preterm labor associated with intrauterine infection contains increased concentrations of cytokines. The mechanism underlying this association may be a cytokine-mediated stimulation of amnion cell prostaglandin production. The biosynthesis of prostaglandins from arachidonic acid is regulated by the enzyme cyclooxygenase which exists in two forms; the constitutive form (COX-1) and the other mitogen inducible (COX-2). The purpose of this study was to evaluate the effect of the cytokine interleukin-4 (IL-4) on cyclooxygenase activity and PGE2 production in amnion. Amnion tissue was taken at caesarean section from term women not in labor and immediately incubated for 2 hours in media containing concentrations of IL-4 ranging from 1 to 100 ng/ml. An increase in both COX-2 enzyme and prostaglandin E2 (PGE2) production was observed for all concentrations of IL-4 greater than 25 ng/ml (P < 0.05, n = 8). No change in COX-1 was observed. Our data suggest that the cytokine IL-4 may be involved in the pathogenesis of premature labor by inducing COX-2 in amnion tissue resulting in increased production of PGE2 and subsequent myometrial activity.

Amnion↗

Serial intravaginal prostaglandin E2 gel cervical ripening in preterm pregnancies.

OBJECTIVE: To determine if prostaglandin (PG) E2 cervical ripening is safe and effective in high-risk preterm pregnant women who do not have an indication for immediate delivery. METHODS: This was a retrospective case-control study of preterm pregnant women treated with sequential PGE2 gel between 3/1/92 and 3/1/95. Study subjects were between 24 and 36 weeks gestation, had intact membranes, and complications requiring inpatient monitoring but not immediate delivery. PGE2 gel was inserted serially until either maternal or fetal deterioration required intervention, fetal maturity was achieved, a Bishop > or = 7 was reached, or the patient improved and was discharged. Control subjects were matched for inclusion criteria and diagnoses on admission. RESULTS: A total of 22 study and 22 control patients were evaluated. The gestational age at admission was 32.3 +/- 2.8 versus 31.8 +/- 2.9 weeks. The mean number of PGE2 gel applications was 11.6 over a mean of 5.0 days. Intervention during ripening was required in 11 (50%). A Bishop score > or = 7 without labor was achieved in 11 (50%), and labor during the ripening process occurred in 2 (9%). The mean time from Bishop > or = 7 to delivery was 2.6 days. The total cesarean delivery rate was 10 (45%) versus 15 (68%), in the control group (P = NS). Neonatal outcomes were similar. CONCLUSIONS: Sequential PGE2 gel cervical ripening when used in preterm pregnant women improves the Bishop score, and has a low incidence of spontaneous preterm labor.

Administration, Intravaginal↗

The expression of cyclooxygenase-2 (COX-2) in amnion and decidua following spontaneous labor.

OBJECTIVE: Prostaglandins production rises dramatically during term and preterm labor. The source of this production is thought to be the fetal membranes and maternal decidua. The enzyme responsible for the conversion of arachidonic acid to the prostaglandins and related endoperoxides is variously known as prostaglandin synthase or cyclooxygenase (COX). An inducible form of this enzyme, COX-2, has been described in several tissues. The purpose of this study was to investigate a possible role for COX-2 in labor by comparing the COX-2 content in amnion and decidua from laboring and non-laboring patients. STUDY DESIGN: Fetal membranes from seven normal labor and ten elective cesarean sections at term were collected immediately following delivery. The maternal age and gravity were similar between the groups. The amnion and decidua were identified, washed in sterile saline, frozen in liquid nitrogen and stored in -70 degrees C. COX-2 expression was determined using Western Blot analysis with a purified COX-2 antibody. A scanning densitometer was used to quantify the bands. Results were expressed as mean +/-S.D. ng/50 micrograms protein. RESULTS: The concentration of COX-2 in amnion of laboring women showed a twofold increase (240.0 +/- 17.6 vs. 120.7 +/- 5.1) compared to the non-labored group (p < 0.05). The concentration in the decidua showed no significant increase during labor (38.1 +/- 7.5 vs. 26.4 +/- 2.1, p > 0.05). CONCLUSION: We evaluated the role of COX-2 in normal labor. Our study demonstrates that COX-2 is significantly induced in the amnion following spontaneous labor. These findings suggest that the induction of amnion COX-2 may be involved in the process of human labor.

Amnion↗

Cerebral palsy, perinatal depression and low ponderal index.

To determine whether asymmetric growth restriction, abnormally lean body morphology, is associated with cerebral palsy (CP) in infants born with perinatal depression, perinatally depressed Collaborative Perinatal Project infants were assessed. Rates of ponderal index less than 5% for gestational age and race (low PI), a marker for asymmetric growth, were compared in infants either neurologically normal or having CP at 7 years of age. Low PI was associated with CP in infants with Apgar scores of 0 to 3 at 10, 15 or 20 minutes in both of these groups, after exclusion of small-for-gestational-age infants, and was a significant individual correlate of cerebral palsy with multiple logistic regression. The attributable risk of cerebral palsy related to low Pl was 12.4%.

Apgar Score↗

The effect of magnesium sulfate on bleeding time in pregnancy.

OBJECTIVE: The bleeding time is one of the most commonly used diagnostic tests to evaluate platelet-related hemorrhagic disorders. Magnesium has been shown in vitro to be a platelet antiaggregant. This study was conducted to evaluate the hypothesis that magnesium sulfate has no effect on the template bleeding time. STUDY DESIGN: The study group consisted of 24 women who required magnesium sulfate in pregnancy. A blood cell count, platelet count, magnesium level, bleeding time, and mean arterial pressure were obtained before and 2 hours after magnesium sulfate infusion. Magnesium sulfate was infused beginning with a 6 gm intravenous bolus followed by 2 gm/hr. A template bleeding time was performed with a Simplate-II (Organon Teknika, Durham, N.C.) device. Two of the authors performed all the bleeding times. Data were analyzed with a paired t test and Wilcoxon rank test. RESULTS: Fifteen (63%) patients received magnesium sulfate for tocolysis or before external cephalic version and nine (37%) for preeclampsia prophylaxis. No differences were found between the normotensive and hypertensive groups regarding maternal age, gestational age, initial bleeding time, or platelet count. Analysis of the entire study group revealed a prolongation of the bleeding time after magnesium sulfate (5.7 +/- 1.8 vs 6.6 +/- 1.9 minutes, p < 0.05); a lowering of the mean arterial pressure (p < 0.05), and a rise in the magnesium level (p < 0.05). Four patients (16.7%) had a postmagnesium bleeding time > 9 minutes. CONCLUSION: Magnesium sulfate appears to prolong the bleeding time in pregnancy. The clinical significance remains to be determined.

Adult↗

Pre-induction cervical ripening: a randomized comparison of two methods.

OBJECTIVES: To compare two methods of pre-induction cervical ripening in a randomized clinical trial. METHODS: A single intracervical prostaglandin E2 (PGE2) gel application was compared with a single insertion of hygroscopic dilators in 441 women at term with unfavorable cervical scores. Induction success was defined as entry into active labor within 6 hours of oxytocin infusion. RESULTS: There was no statistical difference in pre- or post-ripening cervical scores. In the group receiving hygroscopic dilators, only 28% entered the active phase of labor within 6 hours of oxytocin infusion compared with 45% (P < .001) in the PGE2 group. Thus, in this study, a change in cervical score did not directly predict induction success. There was a higher rate of postpartum endometritis (24 versus 14%; P = .007) and suspected neonatal infection (10 versus 5%; P = .03) in the dilator group. CONCLUSIONS: Pre-induction ripening by hygroscopic dilators and intracervical PGE2 was equivalent as measured by changes in the cervical score. The change in cervical score, however, was not predictive of successful induction, and PGE2 was more frequently associated with induction success. Hygroscopic dilators were associated with a higher incidence of postpartum maternal and neonatal infection because of a longer duration of labor. Hospital charges for intracervical PGE2 gel totaled $522 compared with $91 for the insertion of three dilators.

Administration, Intravaginal↗

The effect of sample preparation and storage on maternal triple-marker screening.

OBJECTIVE: To evaluate the effect of different sample collection, storage, and preparation techniques on serum alpha-fetoprotein (AFP), beta-hCG, and unconjugated estriol (E3) concentrations. METHODS: A solution containing known concentrations of AFP, hCG, and unconjugated E3 was diluted in blood samples obtained from seven healthy male volunteers. Serum from each blood sample was removed immediately, and either assayed or frozen at -70C. Portions of the remaining blood were handled as follows: centrifuged and refrigerated, centrifuged and left at room temperature, not centrifuged and refrigerated, or not centrifuged and left at room temperature. Serum was removed from these samples for triple-marker analysis at 24, 48, 96, and 168 hours after the initial sample collection. RESULTS: Immediate freezing of serum and subsequent thawing resulted in a significant increase in beta-hCG and unconjugated E3 levels, but no change in AFP levels. There was a significant effect over time on AFP, hCG, and unconjugated E3 concentrations. The change in AFP levels was influenced by centrifugation status, whereas all three analytes were influenced by refrigeration status. CONCLUSION: Different sample collection, storage, and preparation techniques may affect maternal triple-marker screening.

Chorionic Gonadotropin↗

Outpatient oral sulindac to prevent recurrence of preterm labor.

OBJECTIVE: To assess the efficacy and safety of oral sulindac in preventing the recurrence of preterm labor. METHODS: This was a randomized, double-blind, placebo-controlled study of patients between 24-34 weeks' gestation with preterm labor treated with intravenous magnesium sulfate. After successful tocolysis, patients were randomized by the pharmacy to receive either oral sulindac (200 mg) or placebo (once orally every 12 hours) for 7 days. RESULTS: Sixty-nine patients were enrolled (34 in the sulindac group, 35 controls). No significant differences were found with respect to time gained in utero (40 +/- 4.4 versus 31 +/- 3.4 days, P = .1), delivery at more than 35 weeks' gestation (20 versus 18, P = .70), recurrent preterm labor (11 versus 13, P = .88), birth weight (2528 +/- 646 versus 2459 +/- 707 g, P = .68), or time spent in the neonatal intensive care unit (4.2 +/- 12.9 versus 5.7 +/- 13.5 days, P = .63) for the sulindac and control groups, respectively. However, in women who failed therapy (ie, those who delivered before 37 weeks' gestation or required readmission for tocolysis), there was a significantly longer interval between the start of therapy and failure in the sulindac group (25.9 +/- 3.4 days, n = 26) than in the control group (15.2 +/- 2.8 days, n = 25; P < .05). CONCLUSION: The use of oral sulindac for 1 week after successful parenteral tocolysis failed to reduce the overall rate of preterm birth. In women who delivered prematurely or required readmission for tocolysis, oral sulindac significantly prolonged the interval from the start of therapy until delivery or readmission. Moreover, this benefit was achieved without observable adverse effects on the fetus.

Administration, Oral↗

Estrogen-induced guinea pig model for uterine leiomyomas: do the ovaries protect?

A guinea pig model was used to study the hormonal control of uterine leiomyomas. Twenty female guinea pigs were divided into four groups--young, old, ovariectomized (OVX), and non-OVX animals--and were given two estradiol-17 beta (E2) silastic implants each for 3-10 mo; another four older OVX animals served as controls and received empty implants. After 3 mo, 100% (8 of 8) of the OVX animals, but none of the OVX controls, developed tumors, mainly on the uterine serosa and the abdominal wall. Electron microscopy and desmin immunostaining demonstrated that the tumors were leiomyomas. In E2-treated animals, E2 levels in serum, leiomyomas, or leiomyoma-free uterine segments rose significantly while serum progesterone (P4) was negligible. Surprisingly, only 8% (1 of 12) of the non-OVX animals developed a tumor. This apparent "ovarian protection" was transient: after 6-9 mo, 50% of the remaining non-OVX animals developed leiomyomas, but these were smaller and fewer than in OVX animals. On the basis of this model, we propose the hypothesis that some factors from the ovaries suppress leiomyoma growth in response to estrogen but that as the ovaries age this protection is diminished, allowing the clinical development of leiomyomas.

Animals↗