Rapid prenatal diagnosis of aneuploidy from uncultured amniotic fluid cells using five-colour fluorescence in situ hybridization

In this paper we describe the use of five-colour fluorescence in situ hybridization for prenatal diagnosis of aneuploidy using uncultured amniotic fluid cells. The analysis is based on ratio mixing of dual-labelled probes and digital imaging for the detection and visualization of five different probes specific for the five target chromosomes, 13, 18, 21, X, and Y. A retrospective blind analysis of 30 coded uncultured amniotic fluid samples correctly detected fetal sex and five trisomy 21 cases. Multicolour fluorescence in situ hybridization used in this way allows rapid and simultaneous detection of the most frequent aneuploidies.     

Flow cytometric method to measure urea-resistant alkaline phosphatase from blood neutrophils for use in the prenatal screening of Down's syndrome

The histochemical measurement of urea-resistant alkaline phosphatase from maternal blood neutrophils is known to have a high detection rate for the prenatal detection of Down's syndrome pregnancies. However, because the histochemical method is laborious and subjective to use, it has not gained widespread acceptance in prenatal screening programmes. We present a simple and objective method for the measurement of urea-resistant alkaline phosphatase by flow cytometry. The method should allow the design of larger studies aimed at evaluating the role of neutrophil urea-resistant alkaline phosphatase in the prenatal screening for Down's syndrome.     

Achondrogenesis type 2 diagnosed by transvaginal ultrasound at 12 weeks' gestation

Ultrasound examination at 12 weeks' gestation revealed severe generalised subcutaneous oedema in a pregnancy at risk for achondrogenesis type II. Transvaginal scanning confirmed the oedema and suggested abnormal limb development. The prenatal diagnosis was confirmed by X-ray examination after transvaginal termination.     

Serum PAPP-A levels are depressed in women with fetal Down syndrome in early pregnancy

The value of maternal serum pregnancy-associated plasma protein (PAPP)-A in screening for Down syndrome in early pregnancy was assessed using stored samples. Seventeen cases of Down syndrome and 66 unaffected control pregnancies were studied. The median PAPP-A level in the cases was 0.42 multiples of the expected value in controls (p <0.0001). Eleven cases (65 per cent) had levels less than half the expected value compared with only six controls (9 per cent). A commercial assay kit is now needed so that prospective screening with this marker can begin.     

Expanding multiple marker screening for Down's syndrome to include Edward'S syndrome

Information on maternal age and maternal serum alpha-fetoprotein, unconjugated oestriol (uE₃), and human chorionic gonadotrophin (hCG) levels was used to investigate retrospectively the effect of estimating Edward's syndrome risk in women having multi-marker screening for Down's syndrome. The screened population comprised 15 pregnancies affected by Edward's syndrome, 15 with Down's syndrome and 5472 unaffected pregnancies. The use of all three markers to estimate Edward's syndrome risk would have led to the detection of 10–12 (67–80 per cent) cases with a false-positive rate of 0.3–0.6 per cent depending on the risk cut-off. A further case would have been detected as a result of screening for Down's syndrome alone. Similar results were obtained when the Edward's syndrome risk was based on uE₃ and hCG only. These data suggest that extending Down's syndrome screening to include Edward's syndrome risk will yield a high detection rate with only a small increase in the false-positive rate.     

Continuous subcutaneous insulin infusion (CSII) in pregnant diabetic patients

The efficacy of the insulin infusion pump (CSII) in pregnancy was examined in 12 diabetic patients and compared with intermittent insulin therapy (IIT). In patients poorly controlled on IIT constant and rapid equilibrium was achieved with CSII (mean of glucose levels: CSII versus IIT=84 versus 137 mg/dl; S.D. = 36 versus 63 mg/dl; mean amplitude of glycemic excursion (MAGE)=65 versus 112 mg/dl. In patients well controlled on IIT, CSII led to a reduction in the variation of glucose excursions (S.D.= 29 versus 36 mg/dl; MAGE=48 versus 76 mg/dl). CSII generally produced a reduction of 20–37 per cent of daily insulin dose (in three cases there was an increase of dose with the achievement of glycemic control). Furthermore in CSII treated-patients amniotic glucose, insulin and C-peptide concentrations werefound tobeinthenormalrange(22.1±10.1 mg/dl; 5.2±2.7μ/ml; 1.25±0.71 ng/ml, respectively). All infants were horn at or near-term, had no macrosomia or neonatal problems. It is concluded that CSII is a highly efficient way to achieve normal glucose levels in pregnancy, not only in type I, hut also in type II or gestational diabetes.     

The electromotor system of Torpedo

The electric organ of Torpedo, besides providing abundant amounts of cholinoceptive post-synaptic membrane for the isolation of the acetylcholine receptor protein, is a rich source of cholinergic nerve terminals. Using perfused, innervated tissue blocks from which synaptic vesicles in different functional states can be isolated, much information can be obtained about synaptic-vesicle dynamics. So far this is consistent with the view that the synaptic vesicles are the source of transmitter released on stimulation and that uptake of newly synthesized transmitter by the vesicles is dependent on their having discharged their previous charge of transmitter in at least one cycle of exo- and endocytosis. Studies of the protein composition of the vesicle membrane, especially when combined with similar information about the external presynaptic membrane, purified samples of which are now available from synaptosome (T-sac) preparations, promise to throw new light on the molecular mechanism underlying vesicle exo-/endocytosis.