The genital tract immune milieu: an important determinant of HIV susceptibility and secondary transmission.

HIV is generally sexually acquired across the genital or rectal mucosa after exposure to the genital secretions of an HIV-infected partner. Most exposures to HIV do not result in infection, likely due to protection afforded by an intact mucosal epithelium, as well as by innate and adaptive mucosal immune factors present in the genital tract. Another important mucosal determinant of transmission may be the number and activation status of potential HIV target cells, including CCR5/CD4+ T cells and DC-SIGN+ dendritic cells. The simultaneous presence of other genital infections, including classical sexually transmitted infections (STIs), can enhance HIV susceptibility either by breaching the epithelial barrier, recruiting HIV target cells to the genital tract, or by generating a pro-inflammatory local immune milieu. In HIV-infected individuals, genital co-infections increase HIV levels in the genital secretions, thereby increasing secondary sexual transmission. Co-infections that act as important HIV cofactors include human cytomegalovirus (CMV), Herpes simplex virus type 2 (HSV2), Neisseria gonorrhoeae and many others. Strategies focused on genital co-infections, such as vaccines, microbicides and suppressive therapy, are feasible in the short term and have the potential to curb the pandemic.

A multicenter controlled trial of fetal pulse oximetry in the intrapartum management of nonreassuring fetal heart rate patterns.

OBJECTIVE: Recent developments permit the use of pulse oximetry to evaluate fetal oxygenation in labor. We tested the hypothesis that the addition of fetal pulse oximetry in the evaluation of abnormal fetal heart rate patterns in labor improves the accuracy of fetal assessment and allows safe reduction of cesarean deliveries performed because of nonreassuring fetal status. STUDY DESIGN: A randomized, controlled trial was conducted concurrently in 9 centers. The patients had term pregnancies and were in active labor when abnormal fetal heart rate patterns developed. The patients were randomized to electronic fetal heart rate monitoring alone (control group) or to the combination of electronic fetal monitoring and continuous fetal pulse oximetry (study group). The primary outcome was a reduction in cesarean deliveries for nonreassuring fetal status as a measure of improved accuracy of assessment of fetal oxygenation. RESULTS: A total of 1010 patients were randomized, 502 to the control group and 508 to the study group. There was a reduction of >50% in the number of cesarean deliveries performed because of nonreassuring fetal status in the study group (study, 4. 5%; vs. control, 10.2%; P =.007). However, there was no net difference in overall cesarean delivery rates (study, n = 147 [29%]; vs. control, 130 [26%]; P = .49) because of an increase in cesarean deliveries performed because of dystocia in the study group. In a blinded partogram analysis 89% of the study patients and 91% of the control patients who had a cesarean delivery because of dystocia met defined criteria for actual dystocia. There was no difference between the 2 groups in adverse maternal or neonatal outcomes. In terms of the operative intervention for nonreassuring fetal status, there was an improvement in both the sensitivity and the specificity for the study group compared with the control group for the end points of metabolic acidosis and need for resuscitation. CONCLUSION: The study confirmed its primary hypothesis of a safe reduction in cesarean deliveries performed because of nonreassuring fetal status. However, the addition of fetal pulse oximetry did not result in an overall reduction in cesarean deliveries. The increase in cesarean deliveries because of dystocia in the study group did appear to result from a well-documented arrest of labor. Fetal pulse oximetry improved the obstetrician's ability to more appropriately intervene by cesarean or operative vaginal delivery for fetuses who were actually depressed and acidotic. The unexpected increase in operative delivery for dystocia in the study group is of concern and remains to be explained.

Studies on the in vitro assembly of a beta 1-40: implications for the search for a beta fibril formation inhibitors.

The progressive deposition of the amyloid beta peptide (Abeta) in fibrillar form is a key feature in the development of the pathology in Alzheimer's disease (AD). We have characterized the time course of Abeta fibril formation using a variety of assays and under different experimental conditions. We describe in detail the morphological development of the Abeta polymerization process from pseudo-spherical structures and protofibrils to mature thioflavin-T-positive/Congo red-positive amyloid fibrils. Moreover, we structurally characterize the various polymorphic fibrillar assemblies using transmission electron microscopy and determine their mass using scanning transmission electron microscopy. These results provide the framework for future investigations into how target compounds may interfere with the polymerization process. Such substances might have a therapeutic potential in AD.

Comparison of the modified biophysical profile to a "new" biophysical profile incorporating the middle cerebral artery to umbilical artery velocity flow systolic/diastolic ratio.

OBJECTIVES: The objective of this study was to determine whether the addition of the middle cerebral to umbilical artery systolic/diastolic velocity waveform ratio to the modified biophysical profile would improve perinatal outcome in patients at high risk. STUDY DESIGN: A prospective, randomized outcome study of patients referred to the perinatal laboratory for antenatal surveillance was undertaken. Six hundred sixty-five patients were randomized to two antenatal surveillance protocols: group 1, modified biophysical profile; and group 2, modified biophysical profile plus evaluation of the middle cerebral artery to umbilical artery systolic/diastolic ratio. Patients were followed up serially and neonatal outcome data including gestational age at delivery, birth weight, incidence of cesarean section delivery for fetal distress, admission to the neonatal intensive care unit, days in the neonatal intensive care unit, and the presence of significant neonatal morbidity were tabulated. RESULTS: The total population showed no statistical difference in outcome parameters between groups 1 and 2. However, a subgroup of patients evaluated for suspected uteroplacental insufficiency did show a significant reduction in caesarean section for fetal distress in group 2 patients. CONCLUSIONS: In a subgroup of patients at risk for uteroplacental insufficiency, the addition of the middle cerebral/umbilical artery ratio to an antenatal surveillance protocol should be expected to improve perinatal outcome.

Treatment of acardiac twinning.

BACKGROUND: The twin reversed-arterial-perfusion sequence is a complication of monochorionic twin pregnancies characterized by the hemodynamic dependence of a "recipient" twin from a "pump" twin. The recipient twin exhibits lethal abnormalities including acardia and acephaly. The pump twin has a mortality rate of 50% as a result of high-output heart failure. CASE: The blood supply to an acardiac-acephalus twin was interrupted at 24 weeks' gestation using endoscopic laser coagulation. The co-twin was delivered at 35 weeks and had an uneventful neonatal course following correction of a persistent patent ductus arteriosus. Review of the literature reveals 22 cases of acardiac twinning treated with invasive procedures, seven of them using endoscopic laser coagulation. Pump twin mortality with fetal surgery was 13.6% in comparison with 50% mortality with expectant management (P < .001). CONCLUSION: Fetal surgery is the best available treatment for acardiac twinning. Endoscopic laser coagulation at or before 24 weeks and endoscopic or sonographic guided umbilical cord ligation after this gestational age seem to be the best treatments for this condition.

Multicenter randomized clinical trial of home uterine activity monitoring: pregnancy outcomes for all women randomized.

OBJECTIVE: Our purpose was to evaluate the impact of home uterine activity monitoring on pregnancy outcomes among women at high risk for preterm labor and delivery. STUDY DESIGN: Women at high risk for preterm labor at three centers were randomly assigned to receive high-risk prenatal care alone (not monitored) or to receive the same care with twice-daily home uterine activity monitoring without increased nursing support (monitored). There were 339 women with singleton gestations randomized with caregivers blinded to group assignment. The two groups were medically and demographically similar at entry into the study. RESULTS: Women in the monitored group had prolonged pregnancy survival (p = 0.02) and were less likely to experience a preterm delivery (relative risk 0.59; p = 0.04). Infants born to monitored women with singleton gestations were less likely to be of low birth weight (< 2500 gm; relative risk 0.47, p = 0.003), and were less likely to be admitted to a neonatal intensive care unit (relative risk 0.5, p = 0.01). CONCLUSION: These data show, among women with singleton gestations at high risk for preterm delivery, that the use of home uterine activity monitoring alone, without additional intensive nursing care, results in improved pregnancy outcomes, including prolonged gestation, decreased risk for preterm delivery, larger-birth-weight infants, and a decreased need for neonatal intensive care.

Comprehensive ultrasound examination in a private perinatal practice.

A retrospective review of the types of patients seen and the accuracy of the diagnosis made was undertaken for patients referred for comprehensive ultrasound examination in a large private perinatal practice. A review of the perinatal ultrasound database, neonatal intensive care database, and hospital charts was done in 1338 patients referred to the perinatal ultrasound laboratory for comprehensive ultrasound examination during a 2-year period. Accuracy of the ultrasound diagnosis and relationships between structural anomalies seen on ultrasound examination and perinatal outcome was undertaken. Positive and negative predictive values for the ultrasonic diagnosis were 82% and 98%, respectively. There were 19 (1.4%) false-positive diagnoses and 38 (2.8%) false-negative diagnoses. There was a high correlation between structural anomalies and chromosomal anomalies, with 15 of the 87 infants (17.2%) with structural anomalies also having chromosomal anomalies. The accuracy of ultrasonic diagnosis for comprehensive examinations in a large private perinatal practice compared favorably with previous reports in the literature. The information presented in this study should be helpful to obstetric centers with similar patient populations.

Multicenter randomized clinical trial of home uterine activity monitoring for detection of preterm labor.

Home uterine activity monitoring has been described as an effective means of detecting uterine contractions, but controversy exists whether it is home uterine activity monitoring or increased nursing support in conjunction with it that contributes to earlier detection of preterm labor. In this study 377 women at risk for preterm labor from three centers were prospectively, randomly assigned to high-risk prenatal care alone (not monitored) or to the same care with twice-daily home uterine activity monitoring without increased nursing support (monitored). The two groups were medically and demographically similar at entry into the study. Routine visits, nonroutine visits, and gestational age at diagnosis of preterm labor were similar in both groups. Preterm labor occurred in 41 of 198 monitored and 39 of 179 not monitored patients. Mean cervical dilatation was 1.4 cm in 41 monitored compared with 2.5 cm for 37 not monitored (p = 0.0006); 73.1% of monitored and 27.5% of not monitored had preterm labor detected before 2 cm dilatation (p = 0.00009). Neonatal outcome of singleton pregnancies showed greater birth weight, fewer days in the neonatal intensive care unit, and fewer babies requiring oxygen therapy and mechanical ventilation in the monitored group. The better outcomes are probably due to the increased likelihood of diagnosis of preterm labor before advanced cervical dilatation with home uterine activity monitoring, thus providing the clinician with a better chance to initiate tocolytic therapy directed at improving pregnancy outcome.

Umbilical cord cyst presenting as an omphalocele at 15 weeks' gestation. A case report.

A small, cystic structure was identified on a routine ultrasound scan performed for dating at 15 weeks' gestation. Originally it was thought to be an omphalocele, but further examination confirmed its origin in the cord several centimeters distal to the fetus. Close scrutiny of ultrasonograms is important since technical capabilities permit high-resolution scans during early gestation.

Maternal serum Down syndrome screening: unconjugated estriol is not useful.

Study of 41 known Down syndrome cases and 441 matched controls did not confirm earlier reports that low unconjugated estriol levels can be used to detect fetal Down syndrome. Hence the obstetric community should exercise caution in using unconjugated estriol levels as a marker in prenatal Down syndrome screening.

Formation of hydroxyeicosatetraenoic acids (HETE) in blood from adults versus neonates: reduced production of 12-HETE in cord blood.

Hydroxyeicosatetraenoic acids (HETE) are major arachidonic acid metabolites of a number of cells found in blood and blood vessels. These products have been implicated in physiologic responses as diverse as platelet aggregation, cell migration, and cell proliferation. Using a sensitive and specific assay, GC/selected ion monitoring after high-performance liquid chromatography separation, we have measured the levels of three HETE isomers of biologic significance 12-HETE, 15-HETE, and 5-HETE in plasma, serum and stimulated serum (formed in the presence of arachidonic acid and calcium ionophore), obtained from normal adults and cord blood from normal neonates. Whereas there were no significant differences between the two groups for 5- or 15-HETE in any of the samples, stimulated serum from adults produced 12 times as much 12-HETE when compared to cord blood. When platelets were isolated from adult and cord blood, 12-HETE production by neonatal platelets, stimulated with 10 microM arachidonic acid, was less than one-fourth that of adults. Although no role for 12-HETE in normal platelet responses has yet been established, it has been reported that those individuals with myeloproliferative syndromes who demonstrate a concomitant decrease in platelet 12-HETE synthetic ability have an increased bleeding tendency. It needs to be further evaluated if this already depressed level of 12-lipoxygenase in neonatal platelets may contribute to pathologic bleeding in those infants subjected to additional stress (such as prematurity or birth asphyxia).

Rapid development of nephrotic syndrome, hypertension, and hemolytic anemia early in pregnancy in patients with IDDM.

In recent years, the prognosis for a successful pregnancy has greatly improved for women with insulin-dependent diabetes mellitus (IDDM) who are under good glycemic control and free of complications such as vascular disease and nephropathy. We report the rapid development of severe nephrotic syndrome, malignant hypertension, and microangiopathic hemolytic anemia during the first trimester of pregnancy in a 29-yr-old woman with IDDM of 18 yr duration. Our patient had no pregestational history of retinopathy or hypertension and only minimal proteinuria. Significant improvement in blood glucose levels had been achieved over the 6 mo before conception. Kidney biopsy performed before the termination of pregnancy at 10 wk gestation revealed diabetic nephropathy. No other etiology for her renal disease could be found. An arteriole was noted to have entrapped red blood cell fragments and platelet thrombi, revealing the probable source of her hemolytic process. By 8 wk postpartum, her nephrotic syndrome and hemolysis had completely resolved. At 3 mo postgestation, the patient's hypertension was still present but less severe. Her serum creatinine has continued to decrease toward normal. This is the first report of a woman with IDDM in White's classification C who developed a toxemia-like syndrome during the first trimester of pregnancy, attributable to the underlying diabetic state.

Effect of amniotic fluid on platelet thromboxane production.

We have studied the effect of amniotic fluid on thromboxane A2 (TXA2) production as an initial step in an evaluation of the role of this metabolite as the mediator of the pulmonary hypertension that accompanies perinatal aspiration. Term amniotic fluid enhanced platelet thromboxane B2 (TXB2) production in the presence of the aggregating agents thrombin and arachidonic acid, activity being confined to the lipid fraction. Compared with a baseline production of 1.4 +/- 0.45 pmol TXB2/10(6) platelets in response to thrombin (1 U/ml), unfractionated amniotic fluid or its lipid fraction enhanced TXB2 production to 2.87 +/- 0.53 and 2.81 +/- 0.62 pmol, respectively (P less than 0.01). Values for the aqueous extract were no different from buffer control values (1.14 +/- 0.5). No enhancement of platelet TXB2 production was observed in amniotic fluid obtained at 15 to 17 weeks. Similar activity was observed with either adult or neonatal platelets. This thromboxane enhancing property of amniotic fluid appears to be distinct from its thrombin generating property. Following perinatal aspiration, in situ production of thrombin and proaggregatory TXA2 could recruit more platelets, enhance local TXA2 production, and be responsible for the platelet thrombi that have been documented at autopsy in the pulmonary microcirculation in infants with perinatal aspiration syndrome.

Efficacy of maternal screening and therapy in the prevention of chlamydia infection of the newborn.

Routine cervical cultures for chlamydia were obtained during the third trimester of pregnancy to identify infected mothers whose infants may also be infected. The effectiveness of maternal erythromycin therapy in preventing disease due to chlamydia among infants born to these women was also assessed. Clinical outcome of treated mothers and infants was compared to that of untreated subjects. Of 1082 women who were cultured, 85 (7.8%) were positive for chlamydia. Erythromycin therapy was prescribed for 38 of these women. Nasopharyngeal/conjunctival chlamydia cultures were obtained from 16 infants of culture-positive, treated mothers and 21 infants of culture-positive, untreated mothers. None of the infants born to culture-positive, treated mothers developed infection with chlamydia, while five of 21 infants of untreated mothers (p less than 0.04) were culture-positive and symptomatic (four with conjunctivitis, one with pneumonia). On follow-up of the infants born to chlamydia-positive mothers, there was no evidence that chlamydia-infected infants had more frequent episodes of upper respiratory infection and otitis media during the first six months of life. This study demonstrated that diagnosis and treatment of cervical chlamydia infection during the third trimester of pregnancy provides a practical approach to the prevention of infection in the newborn.

Hypertrophic cardiomyopathy and pregnancy: report of a maternal mortality and review of literature.

The first case of maternal mortality with hypertrophic obstructive cardiomyopathy is reported. An additional successfully managed case of hypertrophic obstructive cardiomyopathy and pregnancy is reported. Systemic arterial embolization, which has not been previously reported in hypertrophic obstructive cardiomyopathy with pregnancy is discussed. English language literature on hypertrophic obstructive cardiomyopathy and pregnancy is reviewed, and a management plan has been outlined.

Abnormalities in vascular arachidonic acid metabolism in the infant of the diabetic mother.

The infant of the diabetic mother has an increased incidence of thromboses in utero and in the neonatal period. In the adult with diabetes a decrease in prostacyclin formation has been suggested as a cause for the atherothrombotic tendency. We therefore evaluated arachidonic acid metabolism in infants of diabetic mothers. Endogenous radioimmunoassayable 6-keto prostaglandin F1 alpha (PGF1 alpha) was normal in umbilical vessels obtained from the infants of diabetic mothers whose glucose homoeostasis was maintained when compared with control values. Nevertheless, a significant inhibition of vascular production of 6-keto PGF1 alpha was observed in infants born to mothers with raised HbA1C concentrations. A decrease in the concentration of plasma 6-keto PGF1 alpha was also seen in the infants of diabetic mothers when compared with control neonates. The correlation observed between plasma 6-keto PGF1 alpha concentrations and endogenous vascular prostacyclin formation in the infants of diabetic mothers indicates that the in vitro deficiency of prostacyclin formation reflects a concomitant in vivo abnormality.

Effect of fetal intravascular 4-aminoantipyrine infusions on myometrial activity (contractures) at 125 to 143 days' gestation in the pregnant sheep.

Myometrial activity of low amplitude and long duration--contractures--is present throughout gestation in the pregnant ewe and other species. This activity differs from the contractions of labor and delivery. Between 125 and 143 days' gestation, 4-aminoantipyrine infused into the fetus at rates that produced maternal uterine vein plasma concentrations of 4-aminoantipyrine of 5.95 +/- 1.23 (mean +/- SEM, n = 5) mg X 100 ml-1 markedly depressed both total myometrial electromyographic activity to 28.6% and frequency of contractures to 30.5% of preinfusion values. By 60 minutes of infusion, maternal uterine vein plasma 13,14-dihydro-15-keto prostaglandin F2 alpha concentration was reduced to 14% of the resting level. Two conclusions were drawn from this study. First, prostaglandins are involved in the regulation of contractures. Second, when infusions of 4-aminoantipyrine are used to quantify uterine or umbilical blood flow, the possibility exists that changes will occur in physiologic systems that are modified by prostaglandins.