Christian Schatten

Fetal fibronectin as a selection criterion for induction of term labor

OBJECTIVE We examined whether the presence of fetal fibronectin in cervicovaginal secretions can be used as a selection criterion for induction of labor at term. STUDY DESIGN Cervicovaginal secretions of 64 women who were scheduled for induction of labor were examined for fetal fibronectin and divided into group A (positive for fibronectin) and group B (negative for fibronectin). Both groups were examined for Bishop score, the number of prostaglandin tablets administered, and the interval between induction of labor and delivery. RESULTS In group A the interval between induction of labor and delivery was significantly shorter (p < 0.0001) than in group B. The number of prostaglandin tablets administered to group A was likewise significantly lower (p < 0.0001). Unsuccessful induction of labor only occurred in women with fibronectin-negative cervicovaginal secretions. CONCLUSION The assessment of the fibronectin content of cervicovaginal secretions constitutes a viable instrument in the decision-making process preceding induction of labor.

Prevalence of Cervical and Intrauterine Human Papillomavirus Infected in the Third Trimester in Asymptomatic Women

Objective: To study the prevalence and association of human papillomavirus (HPV) infection in the cervix of pregnant women without visible signs of genital HPV infection undergoing cesarean delivery in the third trimester and to investigate a possible HPV transmission to the fetus. Methods: All women underwent cesarean delivery between 37 and 40 weeks of gestation. Cervical samples were taken prior to cesarean delivery. Furthermore, amniotic fluid, placental tissue, and cord blood were sampled and polymerase chain reaction (PCR) or Hybrid Capture II test (Digene Corp, Beltsville, MD) was performed to detect HPV DNA. Results: We found that 56 (36.6%) of 153 women were positive for HPV in the cervix. Logistic regression analyses showed a decrease of prevalence of HPV infection with increasing maternal age (P = .02). No HPV DNA could be detected in the amniotic fluid or cord blood, whereas eight placental specimens were positive for HPV DNA. Conclusion: The infection rate in women without clinical symptoms of HPV infection is high, but there was no HPV found in the amniotic fluid and in cord blood in women with subclinical infection in the third trimester.

Placental expression and serum concentrations of cytokeratin 19 in preeclampsia.

Objective To evaluate cytokeratin 19 as a serum marker of preeclampsia. Methods Serum cytokeratin 19 levels were measured in 46 women with preeclampsia and 46 controls matched for gestational age and parity, using an immunoradiometric assay. Cytokeratin 19 was evaluated immunohistochemically in placental specimens from 28 healthy pregnant women and 24 women with preeclampsia. Results Cytokeratin 19 was identified in the syncytiotrophoblast in 13 (46.4%) of 28 and 23 (95.8%) of 24 placental specimens from controls and women with preeclampsia, respectively (P = .03). Median serum levels of cytokeratin 19 in controls and women with preeclampsia were 1.7 (range 0.3–4.7) μg/mL and 2.7 (range 0.8–8.2) μg/mL, respectively (P < .001). Cytokeratin 19 significantly influenced the odds of presenting with preeclampsia (P < .001) and the odds of developing severe disease (P < .001). Serum cytokeratin 19 correlated inversely with fetal birth weight (Kendall τ-b correlation coefficient = −0.2, P = .007). Compared with healthy pregnant women, women with severe preeclampsia had significantly higher and more rapidly increasing cytokeratin 19 serum levels throughout the third trimester (P < .001). Conclusion Placental stimulation of cytokeratin 19, and release of it into maternal circulation, seem to be a feature of preeclampsia. Correlations with clinical characteristics suggest that cytokeratin 19 is a marker of disease severity.

Radioimmunoscintigraphy Using Monoclonal Antibodies before Second-Look Surgery in Patients Suffering from Ovarian Cancer

19 patients with a known history of ovarian cancer were investigated by radioimmunoscintigraphy (RIS) to look for recurrent disease a few days before second-look surgery. The tumor-associated monoclonal antibody HMFG-2 (400 micrograms/patient) was injected intravenously after labeling with radioactive 123I (0.5-2.2 mCi/patient). Scans were reviewed for activity accumulations due to uptake of the tumor-associated antibody by tumor sites. In 15 out of the 19 cases the scan results correlated with the intraoperative findings. There were 2 false-positive and 2 false-negative scans, the latter in patients with subclinical disease. The smallest lesion detected by radioimmunoscintigraphy had a diameter of 1.5 cm. In 3 patients, tumor sites were identified that had been missed by all other routinely performed methods of investigation including transmission computed tomography. These data indicate that RIS is of considerable clinical value in the early detection and localization of recurrent ovarian cancer and may, therefore, improve the management of these patients.

Placental expression and serum levels of cytokeratin-18 are increased in women with preeclampsia.

Objective: To evaluate placental expression and serum cytokeratin-18 in women with preeclampsia. Methods: Serum cytokeratin-18 was evaluated in 44 women with preeclampsia and 44 healthy pregnant women using an immunoradiometric assay. Placental expression of cytokeratin-18 was investigated in specimens from 23 women with preeclampsia and 20 healthy pregnant women by immunohistochemistry. Results: Median serum cytokeratin-18 in women with preeclampsia and healthy pregnant women was 106.7 and 76.0 U/L, respectively (P =.02). Among women with preeclampsia, serum cytokeratin-18 was significantly associated with severity of disease (P =.001) and showed a sensitivity (standard error) and specificity (standard error) of 85% (7%) and 65% (12%),respectively. In placental specimens, the cytoplasm of the syncytiotrophoblast stained positive for cytokeratin-18 with strong and widespread staining in 83% and 45% of placental specimens of women with preeclampsia and healthy pregnant women, respectively (P =.01). Conclusion: Elevated serum cytokeratin-18 values are associated with disease severity in women with preeclampsia. OUr data provide additional evidence that the placenta might be the source of the elevated serum cytokeratin-18 values in women with preeclampsia.

Detection of hepatitis C virus (HCV) RNA in normal cervical smears of HCV-seropositive patients

The presence of hepatitis C virus (HCV) in normal cervical smears (CS) obtained from 22 HCV-seropositive and 50 HCV-seronegative patients was assessed by reverse-transcriptase-polymerase chain reaction (RT-PCR). The presence of HCV in serum was established by use of enzyme-linked immunosorbent assay, Western blot test, and RT-PCR. HCV was detected in 36.4% (n=8) of CS cells recovered from 22 HCV-seropositive patients, but not in CS samples obtained from 50 HCV-seronegative patients. Furthermore, cells from the CS of 2 seropositive/smear-positive patients and 1 seropositive/smear-negative patient were isolated; HCV RNA was detectable in the cervical lymphocytes of the 2 smear-positive patients, but not in epithelial cells or granulocytes. HCV RNA is detectable in the CS of some HCV-seropositive women. The clinical importance of these data requires further study.

SERUM LEVELS OF ELAM-1, BUT NOT CD44, PREDICT THE CLINICAL OUTCOME OF PATIENTS WITH PREECLAMPSIA

OBJECTIVE Preeclampsia is a severe complication in pregnancy, causing considerable maternal and fetal morbidity and mortality. Experimental evidence indicates that adhesion molecules are key factors of endothelial activation in preeclampsia. The aim of our study was to evaluate if serum levels of adhesion molecules CD44 and ELAM-1 provide clinically useful information as prognostic markers for preeclampsia. METHODS A matched-pair study including 43 women with preeclampsia and 43 women with uncomplicated pregnancies was performed. Enzyme-linked immunosorbent assay (ELISA) was used to determine serum levels of CD44 and ELAM-1. Results were correlated with clinical data. RESULTS Median serum levels of ELAM-1 in controls and in women with preeclampsia were 8.9 ng/mL (minimum 0, maximum 20.0) and 12.0 ng/mL (minimum 4.0, maximum 27.0), respectively (Kruskal-Wallis test, p = 0.01). In a univariate logistic regression model, ELAM-1 did reveal a significant influence on the odds of presenting with preeclampsia as well as on the odds of premature termination of the pregnancy due to preeclampsia (univariate logistic regression, p = 0.03 and p = 0.01, respectively). The risk of premature termination of the pregnancy was 0.5%, 15.3%, and 80.5% at ELAM-1 serum levels of 0 ng/mL, 10 ng/mL, and 20 ng/mL, respectively. No significant correlation between CD44 serum levels and clinicopathological parameters due to preeclampsia was observed. CONCLUSIONS If these results are confirmed in a larger series, ELAM-1 could be used as a prognostic factor in preeclamptic women, allowing early identification and appropriate management of high-risk patients with preeclampsia. It is unlikely that measurement of ELAM-1 will be of value as a screening test.

Serum levels of leukocyte functional antigen‐3 in pregnancy and preeclampsia

BACKGROUND Adhesion molecules have been demonstrated to be involved in placental growth and development in normal pregnancy. Experimental evidence indicates that adhesion molecules are key factors of endothelial activation in preeclampsia. The aim of our study was to evaluate serum levels of the adhesion molecule Leukocyte Functional Antigen (LFA)-3 in healthy, non pregnant, female controls, healthy pregnant women, and preeclamptic women. METHODS In our study we included 45 healthy, non pregnant, female controls, 45 healthy pregnant women, and 45 preeclamptic women. An enzyme-linked immunosorbent assay was used to determine serum levels of LFA-3. Results were correlated to clinical data. RESULTS The median LFA-3 serum level in healthy, non pregnant, female controls was 0.2 (range 0 to 8.6) ng/mL. LFA-3 serum levels in healthy pregnant women were 4.8 (range 0 to 18) ng/mL and were significantly elevated compared to healthy, non pregnant, female controls (Mann-Whitney U-test, p=0.004). A cut-off level of 4.8 ng/mL was selected according to the 75th quantile of serum levels measured in the panel of healthy, non pregnant, female controls. In preeclamptic women, whose pregnancies had to be terminated due to exacerbation of preeclamptic symptoms, LFA-3 serum levels above the cut-off level were seen in 14/27 (52%) cases. In contrast, preeclamptic women, who went into spontaneous labor showed elevated LFA-3 serum levels in 17/18 (95%) cases (chi-square test, p=0.002). LFA-3 serum levels revealed a statistically significant influence on the odds of termination of pregnancy due to exacerbation of preeclamptic symptoms (unconditional logistic regression, p=0.02) with an odds ratio of 0.1 (95% CI, 0.006 to 0.7) by every doubling of LFA-3 values. CONCLUSIONS Our results suggest that LFA-3 expression is upregulated in healthy pregnant women compared to healthy, non pregnant, female controls. Failure of LFA-3 upregulation in preeclampsia is associated with an increased risk for termination of pregnancy due to exacerbation of preeclamptic symptoms.

Placental Expression of Cytokeratin 18 and Serum Levels of Tissue Polypeptide Antigen in Women with Pregnancy-Induced Hypertension

OBJECTIVE We hypothesized that placental cytokeratin (CK) 18 expression and serum levels of tissue polypeptide antigen (TPA), a surrogate marker for CK 18, are increased among women with pregnancy-induced hypertension (PIH). METHODS Serum levels of TPA were measured in 46 women with PIH and 46 controls, matched for gestational age and parity, using an immunoradiometric assay. Immunohistochemical detection of CK 18 was assessed in placental specimens of 24 women with PIH and 20 controls. Results were correlated to clinical data. RESULTS Cytokeratin 18 expression was found in the syncytiotrophoblast of 7 of 20 (35%) and 18 of 24 (75%) placental specimens of controls and women with PIH, respectively (p = 0.008). Median serum levels of TPA in controls and women with PIH were 93.0 U/L (range: 12.5-281.6) and 154.2 U/L (range: 37.3-496.6), respectively (p = 0.001). Serum levels of TPA significantly influenced the odds of presenting with PIH, as well as the odds of developing severe disease (p = 0.003, and p = 0.001, respectively). TPA values were significantly higher among women with severe PIH compared with women with mild PIH and controls, independent of gestational age (p = 0.004). Among women with severe PIH, serum TPA was inversely correlated with fetal birth weight (r = -0.3; p = 0.001) CONCLUSION Cytokeratin 18 is overexpressed in the syncytiotrophoblast of women with PIH. Serum levels of TPA are elevated among women with PIH and correlate with disease severity and low fetal birth weight.

Synovial phospholipase A2 serum levels in pregnancy and preeclampsia.

Phospholipase A2 (PLA2) is known to act as a regulator of the synthesis and metabolism of prostaglandins and leukotriens. Type II PLA2, i.e., human synovial PLA2 (h-sPLA2), has been found in synovial fluid, endothelial cells, neutrophils, and macrophages. h-sPLA2 is believed to play a functional role in the pathophysiology of rheumatoid arthritis, sepsis, and acute pancreatitis (1). Recently, a model has been proposed for the involvement of h-sPLA2 in the onset and progression of labor via the metabolism of cell membrane glycophospholipids into biologically active, phospholipid-derived mediators (2). Using reverse transcriptase polymerase chain reaction (rt-PCR), hsPLA2 has also been detected in several human gestational tissues including amnion, choriodecidua, and placenta (3). In preeclampsia, h-sPLA2 has been proposed to cause an imbalance in the prostacyclin/thromboxane ratio leading to an increase of thromboxane and to a decrease of prostacyclin, a potent vasodilator and inhibitor of platelet aggregation, in both the maternal and fetal circulations (4). A downregulation of h-sPLA2 activity in umbilical endothelial cell lines of women with preeclampsia compared with healthy pregnant women has been described (5).On the other hand,