Infection and preterm labor.

There are many conditions, such as non-white race, young maternal age, and uterine malformations, that have been associated with preterm birth that are not amenable to intervention. Maternal cervical and intrauterine infection and inflammation may have a primary causative role in a fraction of the cases of preterm birth and preterm rupture of membranes and may also interact adversely with a variety of maternal (shortened cervix, smoking) and fetal factors (polyhydramnios, multifetal gestation) to decrease the threshold to preterm birth. Further studies are needed to better-define the link between various maternal microbial colonizations and preterm delivery, with the possibility to establish new screening and treatment recommendations. Because of the innumerable causes of preterm birth, a new strategy of targeted treatment of cervical or vaginal infections may lead to only a modest reduction in the incidence of this devastating problem of modern obstetrics.

Clinical chorioamnionitis and the prognosis for very low birth weight infants.

OBJECTIVE: To determine the effects of clinical chorioamnionitis on neonatal morbidity and mortality in very low birth weight infants. METHODS: This was an observational cohort analysis of all singleton live-born infants weighing 500-1500 g at 24 weeks' or greater gestational age and born between 1988 and 1996 at Parkland Memorial Hospital, Dallas, Texas. Chorioamnionitis was diagnosed on the basis of maternal fever of 38C with supporting clinical evidence, which included fetal tachycardia, uterine tenderness, and/or malodorous infant, and the absence of another source of infection. Multiple logistic regression analysis was used to adjust for outcomes of interest. RESULTS: Ninety-five of 1367 very low birth weight infants (7%) were exposed to chorioamnionitis. Neonatal sepsis, respiratory distress syndrome, seizure in the first 24 hours of life, intraventricular hemorrhage (grade 3 or 4), and periventricular leukomalacia were all significantly increased with chorioamnionitis, after adjusting for preterm ruptured membranes, pregnancy-associated hypertension, cesarean birth, gestational age, and birth weight. The odds ratios for intraventricular hemorrhage, periventricular leukomalacia, and seizures in the first 24 hours were 2.8 (95% confidence interval [CI] 1.6, 4.8), 3.4 (95% CI 1.6, 7.3), and 2.9 (95% CI 1.2, 6.8), respectively. CONCLUSION: Our results suggest a link between clinical chorioamnionitis and several indices of neonatal morbidity in the very low birth weight infant. Chorioamnionitis appears to make the very low birth weight infant particularly vulnerable to neurologic damage.

Urinary tract infections complicating pregnancy.

Urinary tract infections (asymptomatic bacteriuria, cystitis, and pyelonephritis) are frequently encountered medical complications of pregnancy. The majority of infections in pregnancy are asymptomatic; however, even covert bacteriuria places the mother at risk for low birth weight and preterm birth. Pyelonephritis can result in significant maternal and fetal morbidity and mortality. Therefore, all pregnant women should be screened for asymptomatic bacteriuria, and urinary tract infections should be promptly treated to prevent adverse pregnancy outcome. This article reviews the diagnosis, etiology, treatment, and complications associated with urinary tract infections in pregnancy.

Accumulation of interleukin-1beta and interleukin-6 in amniotic fluid: a sequela of labour at term and preterm.

From the finding of micro-organisms or inflammatory mediators, or both, in amniotic fluid (AF), it has been proposed that intrauterine infection is one cause of preterm labour (PTL, intact fetal membranes). This theory, however, remains unproved, i.e. the accumulation of micro-organisms and inflammatory mediators in AF after labour is in progress may be the consequence, not the cause, of labour both at term and preterm. This study was conducted to evaluate this possibility by a comparison of the concentrations of interleukin (IL)-1beta and IL-6 in AFs collected before and during PTL (<34 weeks gestation) with those in AFs collected at term (before labour and from the forebag and upper compartments of the amniotic sac during labour). The concentrations of IL-1beta and IL-6 in AF were also analysed as a function of the duration of labour (term or preterm) before fluid collection. In addition, studies were conducted to define the source of IL-1beta in AF. A total of 666 AFs were evaluated. IL-1beta was not detected (<50 pg/ml) in AFs collected before the onset of labour at any stage of gestation (n = 320), including 170 fluids obtained at term. During labour, IL-1beta was detected (>50 pg/ml) in 58 out of 106 (54.7%), 17 out of 64 (26.6%) and 60 out of 176 (34%) of AF samples obtained during PTL, term labour (upper compartment) and term labour (forebag) respectively. AF sampling, as well as labour and delivery, were completed in <18 h in all term pregnancies. However, labour (with cervical dilation) was in progress for >18 h before AF was collected in 39 out of 106 (37%) PTL pregnancies. The incidence of IL-1beta-positive samples among AFs collected before 18 h of PTL (23 out of 67; 34%) was indistinguishable from that in AFs collected during labour at term. However, in AFs collected after >18 h PTL, the incidence of IL-1beta-positive samples was 35 out of 39 (89.7%) The concentrations of IL-1beta (pg/ml; mean +/- SEM) in AFs collected during PTL (2680 +/- 730; n = 106) were greater than those in AFs collected from the upper compartment and forebag during term labour (436 +/- 244, n = 64; and 468 +/- 119, n = 176) respectively; this difference, however, was attributable to very high concentrations of IL-1beta in AFs in which PTL was in progress for >18 h before AF collection (6021 +/- 1832; n = 39). The concentrations of IL-6 in AF were correlated with those of IL-1beta (P < 0.001). We conclude that IL-1beta and IL-6 accumulate in AF in a similar proportion of pregnancies during the first 18 h of term and preterm labour. Therefore, the accumulation of these cytokines in AF cannot be taken as evidence for a role for infection in the pathogenesis of PTL.

Cholecystitis in pregnancy.

Biliary tract disease is a relatively uncommon, heterogenous disease in pregnancy. Specifically, acute cholecystitis can be especially difficult to recognize in pregnancy. However, once diagnosed, the initial management plan should be conservative and include antibiotic therapy. Subsequent management depends on the gestational age at diagnosis. Surgical therapy, when indicated, should not be delayed and a planned intervention during the second trimester appears to offer a better outcome than surgery performed under emergent conditions.

Interleukin-1 beta, -1 alpha, and -6 and prostaglandins in vaginal/cervical fluids of pregnant women before and during labor.

Interleukin-1 beta (IL-1 beta) is not detected in the amniotic fluid of normal human pregnancies before the initiation of parturition, but during labor, both at term and preterm, this cytokine is present in the amniotic fluid of 25-40% of pregnancies. A critical question, however, is whether this finding is indicative of a role for IL-1 beta (directly or indirectly) in the initiation of parturition or is the result of IL-1 beta formation and entry into amniotic fluid as a natural sequela of normal labor. The forebag of the amniotic sac is formed during labor in response to cervical dilatation, and on the decidual surface, the tissues of this structure become exposed and bathed by vaginal fluids as the cervix opens. Microorganisms and bacterial toxins are present in vaginal fluid before labor begins; these agents should act upon the exposed tissues of the forebag to cause inflammation and evoke an inflammatory response. This study was conducted to examine the likelihood that the inflammatory mediators found in amniotic fluid in increased amounts at parturition are produced in forebag tissues after the onset of labor because of obliged inflammation in these tissues. Vaginal/cervical fluids were collected by lavage from nonpregnant women and from pregnant women at term before and during labor. The amount of immunoreactive IL-1 beta in vaginal/cervical fluids of pregnant women during labor (mean +/- SEM, 91.5 +/- 16.9 ng; n = 17) was significantly greater (P < 0.001) than that in fluids collected before labor (7.8 +/- 3 ng; n = 14). The in vivo rate of IL-1 beta secretion directly from the decidua lining the forebag during labor was brisk (1.71 +/- 0.88 ng/cm2.min; n = 4), consistent with previous observations of higher levels of pro-IL-1 beta mRNA in decidual tissues adherent to the forebag compared with those in decidua adherent to chorion laeve of the upper compartment of the amnionic sac. The vaginal fluid content of prostaglandins (PGs) during labor [PGE2, 82.1 +/- 16.4 ng; PGF2 alpha, 141.5 +/- 30.5 ng; PGFM, 35.2 +/- 5.8 ng (mean +/- SEM; n = 13)] was significantly greater for PGE2 and PGF2 alpha (P < 0.05 and 0.004, respectively) than that before labor (PGE2, 42.6 +/- 9.4 ng; PGF2 alpha, 35.3 +/- 8.5 ng; PGFM, 21.7 +/- 4.6 ng; n = 12). In addition, there was a significant increase in the ratio of PGF2 alpha to PGE2 (P < 0.03) in vaginal fluids during labor.(ABSTRACT TRUNCATED AT 250 WORDS)

Partial molar pregnancy associated with severe pregnancy-induced hypertension.

Although the natural history of pregnancies associated with complete hydatidiform mole has been well described, the clinical features of partial mole are less consistent. We managed five partial molar pregnancies complicated by severe pregnancy-induced hypertension in the second trimester. We describe the differentiation between complete and partial mole, and the unusual clinical presentation in our patients.

Fetal fibronectin: a method for detecting the presence of amniotic fluid.

OBJECTIVE: To determine whether fetal fibronectin is a sensitive test for the detection of amniotic fluid (AF) in women with rupture of the membranes. METHODS: In a multicenter clinical trial, pooling, ferning, and nitrazine tests were compared with fetal fibronectin in 339 women at term (study group) with a clinical history of rupture of the membranes and in 67 women at term receiving routine prenatal care (controls). Ruptured membranes was diagnosed if any two of the standard tests were positive. Fetal fibronectin in the cervicovaginal secretions was determined using a qualitative enzyme-linked immunosorbent assay test. Fetal fibronectin was considered positive at 50 ng/mL. RESULTS: The sensitivity of fetal fibronectin in the women with ruptured membranes was 98.2%. No controls had ruptured membranes based on standard test results, but 13 women had fetal fibronectin present. The mean (+/- standard error) interval between sampling and delivery was significantly less in the women positive for fetal fibronectin (169.3 +/- 45.8 hours) than in those with no detectable fetal fibronectin (333.4 +/- 29.0 hours). CONCLUSION: Fetal fibronectin is a sensitive test for detection of AF in the vagina and compares favorably to standard tests. Its low specificity suggests that the assay may detect an alteration in membrane integrity. In addition, in patients without rupture of the membranes, the interval between sampling and delivery is significantly shorter if fetal fibronectin is present. We speculate that the presence of fetal fibronectin in cervicovaginal secretions may be a marker for impending labor in gravidas without gross rupture of the membranes.

Histocompatibility screening by molecular techniques: use of polymerase chain reaction products and heteroduplex formation.

Novel molecular approaches have recently become available allowing improved major histocompatibility complex (MHC) matching of potential allogeneic bone marrow donors and recipients. Current cellular and serological assays are hindered by aberrant cell populations and limited reagents which only detect an individuals' phenotype. Therefore, a molecular screening protocol which discriminates at the genotypic level would be advantageous. Here we describe a two-step DNA-based approach that can be applied to large-scale screening of potential donors. A primary screen, utilizing polymerase chain reaction (PCR), reduces the potential donor population, whereas a secondary or fine resolution screen uses DNA heteroduplex analysis to determine identity or non-identity at specific loci. Heteroduplex analysis generates a DNA migration pattern that is unique for alleles at a given locus, and is more sensitive than serology in discriminating among individuals. Here we demonstrate the potential feasibility of this approach by analyzing results at one MHC locus, HLA-DQ. Since this method does not rely on typing sera or viable lymphocytes, it is not subject to the variability found in the traditional methods. In contrast to traditional methods, these molecular techniques can provide the critical information needed to select a potential bone marrow donor.

Ticarcillin/clavulanate in the treatment of pelvic infections.

Ticarcillin/clavulanate was used to treat 130 women with pelvic infections. The 129 who completed an initial course of treatment with ticarcillin/clavulanate were analyzed according to type and clinical severity of infection, and pretreatment and posttreatment endometrial bacteriology. There were 26 cases of pelvic inflammatory disease and 103 puerperal infections, 61 of which occurred in women who had delivered by cesarean section (46 elective with no antibiotic prophylaxis at the time of surgery). Of the 129 patients treated, 124 were clinically cured, and one improved (97%). There were four treatment failures, all of which were among a total of 20 cases classified as clinically severe. All the patients designated as treatment failures required prolonged treatment with other antibacterials to achieve a clinical cure, but a longer duration of treatment with ticarcillin/clavulanate might have effected a clinical resolution even in these cases. In vitro examination of endometrial isolates revealed a significant reduction of the minimum inhibitory concentrations (MICs) of beta-lactamase-producing bacteria with the addition of clavulanate to ticarcillin. The relationship of non-beta-lactamase-producing enterococci having relatively high MICs to clinical failure was examined.

Cachectin/tumor necrosis factor-alpha formation in human decidua. Potential role of cytokines in infection-induced preterm labor.

This study was conducted as part of an investigation to evaluate the hypothesis that bacterial toxins (LPS or lipoteichoic acid), acting on macrophage-like uterine decidua to cause increased formation of cytokines, may be involved in the pathogenesis of infection-associated preterm labor. We found that cachectin/tumor necrosis factor-alpha (TNF-alpha) was synthesized and secreted into the culture medium by human decidual cells and explants in response to treatment with LPS. LPS treatment also caused an increase in PGF2 alpha production by decidual cells and explants. In amnion cells in monolayer culture, TNF-alpha stimulated PGE2 formation, and TNF-alpha was cytostatic (inhibited [3H]thymidine incorporation into DNA) but not cytolytic in amnion cells. TNF-alpha was not detectable (less than 0.34 ng/ml) in the amniotic fluid of normal pregnancies at midtrimester or at term before or after the onset of labor (n = 44); but TNF-alpha was present at concentrations between 2.8 and 22.3 ng/ml in amniotic fluids of 4 of 20 pregnancies with intact membranes complicated by preterm labor (less than 34 wk gestational age). LPS was present in 10 of the 20 amniotic fluids of preterm labor pregnancies, including all four in which TNF-alpha was present. Bacteria were identified in only one of the four LPS-positive, TNF-alpha-positive fluids. Cytokine formation in macrophage-like decidua may serve a fundamental role in the pathogenesis of preterm labor, including increased prostaglandin formation and premature rupture of the membranes.

Recurrent carcinoma in situ of the vulva in a skin graft.

Skinning vulvectomy has been a recommended treatment for carcinoma in situ of the vulva. We report a case of recurrent carcinoma in situ occurring in the skin graft of a patient with previous skinning vulvectomy.

Tubulin assembly sites and the organization of cytoplasmic microtubules in cultured mammalian cells.

The number, distribution, and nucleating capacity of microtubule-organizing centers (MTOCs) has been investigated in a variety of cultured mammalian cells. Most interphase cells contain a single MTOC that is localized at the centrosome region and corresponds to the centriole and pericentriolar material. MTOCs, like centrioles, become duplicated during the S phase of the cell cycle and are equationally distributed to daughter cells in mitosis. Multiple MTOCs were rarely observed in cultured cells except in one cell line (neuroblastoma), which also displayed an equally large number of centrioles in the cytoplasm. The kinetics of microtubule assembly and the tubulin nucleating capacity of MTOCs was assayed by incubating tubulin-depleted, permeabilized 3T3 and simian virus 40-transformed 3T3 cells with phosphocellulose-purified 65 brain tubulin and microtubule assembly buffer. Initiation and assembly of 65 tubulin occurred in association with the cells' endogenous MTOCs, and the length, number, and distribution of microtubules generated about the organizing centers were regulated and cell specific. Our results are consistent with the notion that the specification of microtubule length, number, and spatial arrangement resides largely in the MTOCs and surrounding cytoplasm and not in the tubulin subunits.