Faculty Bibliography

alpha 1-Antichymotrypsin (alpha 1-ACHY) and alpha 1-antitrypsin (alpha 1-AT) are closely related glycoprotein protease inhibitors, present in plasma and other extracellular fluids, that neutralize proteases released by leukocytes in response to trauma and inflammatory stimuli. Both inhibitors are synthesized primarily by hepatocytes, although lower levels of synthesis by monocytes and breast and intestinal epithelial cells have been demonstrated. Recently, the immunohistochemical localization of alpha 1-AT and alpha 1-ACHY in intrauterine and extrauterine human trophoblastic tissue has been reported. In the present study, we have sought to determine whether human trophoblast is also able to synthesize alpha 1-AT and alpha 1-ACHY. Messenger RNA for both inhibitors was found by Northern blotting in chorionic villi obtained from first trimester and term placenta. Substantial differences in messenger levels for both inhibitors among individual placentas were noted. alpha 1-ACHY and alpha 1-AT messenger was also present in trophoblast cells in primary culture. Synthesis of alpha 1-AT and alpha 1-ACHY protein was demonstrated by SDS-PAGE after immunoprecipitation of [35S]-labeled alpha 1-AT and alpha 1-ACHY from conditioned media of trophoblast cells in culture metabolically labeled with [35S]-methionine. It is of some interest that the M(r) of the alpha 1-AT and alpha 1-ACHY secreted by trophoblast were 50,000 and 49,000, respectively, compared with 54,000 and 68,000 for these proteins in plasma (or secreted by HepG2 human hepatoma and MCF-7 human breast cancer cells).(ABSTRACT TRUNCATED AT 250 WORDS)

OBJECTIVE: The purpose of our study was to define further the role of bacterial esterases in amniotic fluid obtained from women with chorioamnionitis. STUDY DESIGN: Amniotic fluid samples from 39 patients with chorioamnionitis were submitted for bacterial cultures and in vitro assay. Esterase inhibitors diisopropyl fluorophosphate and iodoacetic acid were added and the degree of inhibition calculated. These results were compared with the amniotic fluid culture results. Chi square analysis was performed to compare the results of the esterase assay and the inhibition assay between the uninfected and infected amniotic fluid samples. RESULTS: Thirty-one patients had positive bacterial cultures, with 21 being infected with gram-negative organisms. All samples showed significant inhibition (range 55% to 82%) with diisopropyl fluorophosphate. There was partial inhibition with iodoacetic acid (range 10% to 30%) in the gram-negative samples but no inhibition in the gram-positive and uninfected samples. Six infected and two uninfected samples were analyzed by using zone electrophoresis with human plasma as a control. Minimal esterase motility was noted in the amniotic fluid samples as compared with that in plasma. CONCLUSION: The esterases in amniotic fluid appeared to be of bacterial, not human, origin. Furthermore, different groups of bacteria appeared to produce different esterases in infected amniotic fluid

A comparison of multiple factors in the surgical management of cervical incompetence was carried out in 114 procedures. Factors examined included training level of the operator, gestational age, cervical effacement and dilation at the time of operation, diagnostic evaluation, Shirodkar or McDonald procedure, year of the procedure, and tocolytic therapy. The endpoint for successful outcome was defined as 37 weeks or newborn weighing over 2500 gm rather than neonatal survival, thus differing from previous studies. All patients were delivered vaginally unless there was an obstetric indication for cesarean delivery. The most important determinants of a term birth in patients with incompetent cervix were operator experience and the use of a Shirodkar procedure

We calculated the amniotic fluid indexes (AFIs) of 310 women on 459 occasions. Normative data were analyzed and compared with data in several high-risk groups. In the normal gestations there was a progressive increase in AFI with advancing gestation until 32 weeks, after which there was a decline. The mean AFIs in abnormal gestations varied with the clinical diagnoses. These values were compared to those obtained by assessing amniotic fluid volume (AFV), that is a pocket more than 2 cm. There were 51 patients with abnormal AFVs. Forty-two had decreased fluid, six also had decreased AFIs; nine had increased AFVs and five (all with diabetes) also had increased AFIs. Thus, AFIs in normal pregnancies showed an orderly pattern of change with gestational age, and there was no accurate correlation between AFI and AFV. Thus, using AFV alone may lead to false interpretations of amniotic fluid status

OBJECTIVE. To assess the activity of systemic lupus erythematosus (SLE) during pregnancy and to distinguish it from preeclampsia. METHODS. We prospectively measured the complement activation products Ba, Bb, SC5b-9, and C4d, as well as the conventional complement determinants C3, C4, and CH50, during pregnancy in 14 patients with SLE and 10 women with preeclampsia. RESULTS. Four of the 14 SLE patients were considered to have disease flares, 3 occurring in the second trimester and 1 postpartum. In these patients, significant abnormalities of Ba, Bb, SC5b-9, and CH50 were noted. In contrast, measures of C4d did not distinguish between pregnant patients who had flares and those whose SLE remained stable. Although decreased values of C3 were rarely seen in the patients with stable disease, normal values of C3 during lupus pregnancy were not reliably associated with stable disease. Three of 10 non-SLE patients with preeclampsia had elevated levels of Ba; however, in each case, the CH50 level was close to or within the normal range. This was in sharp contrast to the findings observed in the 4 patients with active SLE, in whom high levels of plasma Ba were always associated with low CH50 values. Moreover, the ratio of CH50 to Ba was significantly lower in the patients with lupus flares than in the non-SLE patients with preeclampsia. CONCLUSION. While a decline in the CH50 level alone could otherwise be attributed to decreased synthesis of complement components, these data demonstrate that ongoing activation of the alternative complement pathway can accompany disease flares in pregnant women with SLE

Hydrocephalic women with cerebrospinal fluid shunts are now surviving to reproductive age. Twenty-one pregnancies in 18 patients with shunts, including 11 from the present series and 10 from previous series, were analyzed for neurological, obstetrical, and perinatal outcome. Fourteen women had preexisting shunts, and 4 had the onset of symptomatic hydrocephalus and the placement of shunts during pregnancy. Neurological complications occurred in 13 of 17 (76%) pregnancies in patients with preexisting shunts, including symptoms of increased intracranial pressure (ICP) in 10 of 17 (59%) pregnancies, exacerbation of seizure disorder in 2 of 17 (12%) pregnancies, and severe headaches without increased ICD in 1 patient. In 7 of 11 (66%) of the symptomatic patients, symptoms spontaneously resolved postpartum. Four of 17 (23%) of these pregnancies were associated with shunt obstruction requiring antepartum or postpartum surgery. Four patients had a primary shunt placement, and one had a shunt revision during pregnancy without complications. There were no unusual obstetrical or perinatal complications in the series. The clinical management of pregnant patients with hydrocephalus should include preconception counseling and magnetic resonance imaging, as well as the use of serial antenatal magnetic resonance images, ICP monitoring, or the judicious use of radioisotope studies of shunt patency if signs of increased ICP appear. A cesarean section is recommended for the delivery of the neurologically unstable patient. For asymptomatic mothers, a vaginal delivery with a shortened second stage and prophylactic antibiotics are advised

A total of 3158 patients at greater than or equal to 34 weeks' gestation undergoing nonstress tests and amniotic fluid index determinations were divided into six groups according to the amniotic fluid index and the nature of the decelerations. Fetuses with antepartum decelerations had statistically significantly increased incidences of intrapartum decelerations and operative deliveries because of intrapartum 'distress,' regardless of the amniotic fluid index. They also had significantly increased rates of neonatal acidosis and low Apgar scores when there were 'severe' decelerations and an amniotic fluid index less than 5 in the antepartum period. Thus spontaneous decelerations in reactive nonstress tests with an amniotic fluid index less than 5 may predict fetal compromise