The aim of this study was to evaluate the usefulness of maternal serum markers in the early prenatal diagnosis of molar pregnancies. The ultrasound features, cytogenetic and histopathological findings of 10 cases of molar pregnancy diagnosed at 11-13 weeks of gestation were compared retrospectively with the maternal serum concentrations of human chorionic gonadotrophin (HCG), alpha fetoprotein (AFP), pregnancy-associated plasma protein A (PAPP-A) and pregnancy-specific beta1-glycoprotein (SP1). Free beta-HCG and intact HCG concentrations were very high [> or = 2.5 multiples of the median (MoM)] in all cases. AFP concentrations were extremely low in all cases of singleton complete moles (< or = 0.5 MoM) and were high in one case of twin complete mole, in one case of triploid partial mole and two cases of euploid partial mole (> or = 2.5 MoM). Serum PAPP-A and SP1 were high in complete moles. The combined use of ultrasound features, maternal serum proteins and fetal cytogenetic findings should enable the early differential diagnosis in utero and perinatal management of those molar pregnancies presenting with an anatomically normal fetus.

It has recently been established that maternal serum pregnancy-associated plasma protein A (PAPP-A) was reduced in pregnancies with fetal Down syndrome in the first but not in the second trimester of gestation. In comparison with two other placental proteins, human chorionic gonadotrophin and pregnancy-specific beta 1-glycoprotein, an explanation for this can be formulated based on the large molecular weight of PAPP-A. With the increasing clinical demand for fetal abnormalities to be diagnosed in the first rather than in the second trimester of pregnancy, maternal serum PAPP-A is a strong potential candidate for being used in routine trisomy screening. We have developed a sensitive enzyme immunoassay (ELISA) intended at smaller laboratories due to its long shelf life. Here we show that repeated freezing and thawing, or the addition of iodoacetate (5 mM) did not affect the results, at both high or low concentration of PAPP-A. It is also possible to introduce the serum into the test as a dry sample on blotting paper, easily posted in an envelope. A decrease of 21% was observed after such dry storage for three weeks at room temperature, which can be compensated for by the inclusion of a dried control serum, mailed with the sample(s).

Reduced PAPP-A with increased hCG yields an increased risk in screening for foetal trisomy 21. We confirm recently published observations but do not recommend the establishment of normal medians for IVF pregnancies since the extent of the deviations is varying according to the different stimulation protocols and dosages of gonadotrophins used.

Fourty-four specimens of invasive cancers of the vulva, including 38 primary invasive squamous carcinomas, were analysed by in situ hybridisation with biotinylated HPV 6/11, 16 and 18 DNA probes. Four (9%) of the 44 carcinomas were positive for HPV DNA: three (7%) for HPV 16 DNA and one (2%) for HPV 6/11 DNA. HPV DNA was found only in squamous carcinomas. Of the 38 primary squamous carcinomas, 11% were positive (8% HPV 16, 3% HPV 6/11). The overall 5-year survival was 48.7%, 48.5% for the squamous carcinomas and 50.0% for the HPV DNA positive patients.

Endothelin is the most potent vasoconstrictor peptide known to date. Hormone replacement therapy (HRT) with estrogen reduces plasma endothelin levels. We measured endothelin in 51 postmenopausal patients before and during HRT. Patients were randomly allocated to receive either oral tibolone, oral or transdermal 17 beta-estradiol. A group of comparable volunteers served as controls. After 24 months, endothelin levels decreased in all treatment groups: tibolone, 18.2%; oral 23.1%; transdermal, 20.8%. Endothelin levels increased in the controls by 36.6% (p < 0.01). Tibolone decreases endothelin levels to a similar degree as conventional estrogen-progestogen-replacement therapy. These data provide another potential mechanism supporting the cardioprotective effects of tibolone.

Fresh human placental tissue from deliveries at term was perfused in closed circulation on both the maternal and fetal side. At given times during the 4-hour perfusion period, the amount of human chorionic gonadotropin, human placental lactogen, pregnancy-specific Β₁-glycoprotein and pregnancy-associated plasma protein A was determined in the perfusing buffer. These placental proteins were also quantified in the placental tissue before and after perfusion. Calculations showed that all placentae (n = 3) were able to synthesize all 4 proteins tested.

Pregnancy-associated plasma protein A (PAPP-A) is a large glycoprotein produced mainly by the trophoblast during pregnancy and released into the maternal circulation. Its biological function is unknown. In the second trimester i.e. when Down syndrome (DS) screening is routinely performed, the level of maternal serum PAPP-A was found to be within the normal range in pregnancies affected by fetal trisomy 21. However, PAPP-A was shown to be a potent marker for DS before 14 weeks of gestation. Only radioimmunoassays (RIAs) based on labelled antigen competition reached the required sensitivity for early pregnancy PAPP-A determinations; but they have a very short shelf life due to inherent tracer half-life and, in the case of PAPP-A, instability of the labelled antigen after three weeks. We describe a convenient and novel enzyme immunoassay (ELISA) with high sensitivity and a long shelf life.

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