First trimester diagnosis of methylmalonic aciduria.

We have studied methylmalonyl CoA mutase activity in control chorionic villi to establish the potential use of assays performed directly on this tissue for prenatal diagnosis of methylmalonic aciduria. We report the detection of a fetus affected with the apo-mutase deficient form of this condition at 9 weeks' gestation. Methylmalonyl CoA mutase was markedly deficient in chorionic villi, approximately 2.5 per cent of the mean control value. However, incorporation of label from [14C]-propionate into protein was 10 and 40 per cent of the mean control value, respectively, in two portions of the same biopsy, highlighting potential problems in the use of this indirect assay. Normal results were obtained in chorionic villus samples from four other pregnancies 'at risk' for methylmalonic aciduria which were subsequently shown to be unaffected with this condition. The diagnosis in the affected pregnancy was confirmed by demonstration of a marked deficiency of methylmalonyl CoA mutase activity in villi obtained at termination and in cultured fetal fibroblasts. Reduced incorporation of [14C]-propionate label into protein was also found in these tissues.

Effect of intrauterine contraceptive device on uterine haemostasis: a morphological study.

The effect of the intrauterine contraceptive device (IUCD) on uterine haemostasis was studied at various stages of the menstrual cycle in a series of 46 patients by light- and electron-microscopy and by following the distribution of an infusion of 51Cr-labelled autologous platelets. The endometrium in contact with the IUCD in the majority of cases showed grooving with atrophy and mild chronic inflammation in the surrounding tissues. The adjacent stroma also showed increased vascularity and occasional foci of haemorrhage but the increased blood loss associated with the presence of the IUCD could not be attributed to mechanical erosion or stromal blood vessels by the device. During menstruation the presence of an IUCD does not appear to inhibit the formation of fibrin/platelet thrombi although both in control and IUCD patients there was a striking paucity of platelet/fibrin thrombi in circumstances where their formation should be enhanced. In contrast to other workers we have not observed that gaps or breaks in the endothelial lining of endometrial blood vessels occur with any greater frequency in patients fitted with an IUCD. The principal mechanism by which uterine haemostasis is achieved remains to be established.

Heparin-like activity in uterine fluid.

Uterine fluid was collected from a group of normal patients and a group of patients with menorrhagia. Heparin-like activity was detected in 34 out of 38 samples using an anti-Xa heparin assay. The heparin-like activity in uterine fluid was inhibited by adding the heparin antagonist hexadimethrine bromide to the assay. Concentrations of fibrinogen-fibrin degradation products (FDPs) were measured in five samples of uterine fluid. FDPs in the concentration detected had no effect on the anti-Xa assay. Heparin-like activity was higher in the group with menorrhagia, although the differences were not significant. Heparin-like activity increased throughout the menstrual cycle and decreased during menstruation, suggesting a possible cyclical variation in activity. There was no correlation between mast cell numbers in the endometrium and myometrium and heparin-like activity in uterine fluid and no correlation between the numbers and the stage in the menstrual cycle. In a few patients with intrauterine contraceptive devices (IUCDs) heparin-like activity was increased.