[Evaluation of a programme for the prenatal screening for Down's syndrome by ultrasonographic nuchal translucency measurement and serum determinations in the first trimester of pregnancy]. / Evaluatie van een programma voor prenatale screening op downsyndroom door echoscopische nekplooimeting en serumbepalingen in het eerste trimester van de zwangerschap.

OBJECTIVE: To determine the diagnostic value of the combination screening test for Down's syndrome in women in the first trimester of pregnancy. DESIGN: Secondary data analysis. METHOD: The data from 2026 consecutive combination tests that were carried out in the period 1 May 2001-31 October 2003 in the VU Medical Centre in Amsterdam, The Netherlands, were analysed. The combination test comprised ultrasonographic neck fold measurement together with determination of the serum levels of free human beta-chorionic gonadotrophin and pregnancy-associated plasma protein A. The chance of Down's syndrome in the foetus was calculated using the median values of the Fetal Medicine Foundation (FMF) and medians based on the population in the VU Medical Centre. A chance > or = 1:200 was considered elevated. Follow-up data were collected from the medical records and from patient reports. RESULTS: The data from 25 patients were excluded because of incompleteness of the investigation or the presence of diabetes mellitus in the pregnant subject. Follow-up data were obtained from 1759 of the 2001 remaining women (88%). Of the 1759 women, 49% were < or = 35 years old and 51% were > or = 36 years of age. Down's syndrome was diagnosed in 21 pregnancies, 16 of which were in the advanced maternal age group of patients. The detection percentage of Down's syndrome by nuchal translucency measurement was 67 with 3 false-positives when calculated on the basis of the FMF-medians and 76 with 6 false-positives when calculated on the basis of the VU Medical Centre medians. With the combination test, the detection percentage of Down's syndrome was 86 with 11 false-positives when calculated on the basis of the FMF-medians and 90 with 5 false-positives when calculated on the basis of the VU Medical Centre medians. CONCLUSION: The diagnostic value of the first-trimester combination test was greater than that of only nuchal translucency measurement. Moreover, the diagnostic value was greater if the chances were calculated on the basis of the median values of the VU Medial Centre population than when other median values were used.

Comparison of the antileukemic activity in vitro of dexamethasone and prednisolone in childhood acute lymphoblastic leukemia.

It is generally assumed that prednisolone (PRD) and dexamethasone (DXM) have equal glucocorticoid activity of PRD is given at sevenfold higher doses. Results of clinical studies of childhood acute lymphoblastic leukemia (ALL) suggested that DXM is more potent relative to PRD than assumed. The purpose of this study was to determine the relative antileukemic activity of PRD phosphate and DXM phosphate in 133 untreated childhood ALL samples in vitro, using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium-bromide (MTT) assay. There was a marked variation in antileukemic activity of both agents among the patient samples. The median LC50 (drug concentration lethal to 50% of the ALL cells) for PRD phosphate was 3.50 microM, for DXM phosphate 0.20 microM. The individually calculated ratios of the LC50 values for PRD and DXM phosphate showed a large range from 0.7 to >500, with a median of 16.2. This 16-fold difference could not be explained by differences between these glucocorticoids in stability, hydrolysis into unesterified drug, adhesion to the wall of the microculture plates, or protein binding. ALL cells were cross-resistant to PRD and DXM phosphate (correlation coefficient = 0.85, P<0.000001). We conclude that the in vitro antileukemic activity of DXM phosphate is median 16-fold higher than that of PRD phosphate, which contrasts to the generally assumed factor of 7. Based on the higher potency of DXM, and its more favorable pharmacokinetics as reported in the literature, DXM may be preferred to PRD as the glucocorticoid in the treatment of ALL.

Determination of sorbitol in erythrocytes of diabetic and healthy subjects by capillary gas chromatography.

A gas-liquid chromatographic method, using a fused silica capillary column, for the determination of red cell sorbitol is described. The capillary column gives complete resolution of the polyols xylitol, inositol, mannitol, sorbitol and galactitol, even when the glucose peak in the red cell chromatogram is dominating. The identity of sorbitol, and its single elution from the capillary column has been confirmed by mass spectrometry. Recovery of sorbitol from various red cell samples was 101% +/- 3.2 (mean +/- SD, n = 7). Precision, estimated from duplicate diabetic red cell sorbitol analyses was CVdup = 3.5% (n = 18) and from run to run analyses CVinterassay = 4.0% (n = 6). Sorbitol levels determined in erythrocytes of 19 healthy subjects were 5.9 +/- 1.6 nmol/ml red cells and in erythrocytes of 18 insulin-dependent diabetics 17.8 +/- 8.2 nmol/ml red cells (means +/- SD). The method described offers a reliable and specific tool to study in vivo polyol pathway activity in relation to some diabetes-associated complications.