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Pre-eclampsia is the most common medical complication of pregnancy. Immunologic maladaptation has been suggested to play a role in the etiology of pre-eclampsia. The putative misalliance of fetal trophoblast with maternal tissue in the uteroplacental vascular bed may give rise to an increase in oxygen free radicals. Oxygen free radicals and lipid peroxides might form the link between the hypothetical immunologic maladaptation and the endothelial cell damage known to occur in pre-eclampsia. Recent studies have demonstrated the existence of increased oxygen free radical production in pre-eclampsia. Oxygen free radicals and lipid peroxides decrease vascular prostacyclin and EDRF release and increase thromboxane A2 and endothelin release. The hypothesis is put forward that in pre-eclampsia a proposed immunologic maladaptation causes an increase in oxygen free radicals by decidual lymphoid cells. A decrease in vasodilatory autocoids, prostacyclin and EDRF may result from the endothelial cell damage induced by oxygen free radicals. Uteroplacental prostacyclin production might be essential as escape mechanism. The adequacy as escape mechanism seems to determine the final clinical outcome.

The renin-angiotensin-aldosterone system plays an integral role in the (patho)physiology of pregnancy and pregnancy-induced hypertensive disease. The current review concerns the renin-angiotensin-aldosterone system in relation to other vasoactive substances in normal pregnancy and preeclampsia.

Maternal mortality rates in developed countries have declined steeply during the last 50 years. The introduction of sulphonamides and blood transfusion techniques contributed much to lowering maternal mortality rates. The maternal mortality rate in The Netherlands in 1983-1988 was 8.8/100,000 livebirths. In 57% substandard care factors could be identified. This suggests that further improvement in preventing maternal mortality is possible. Maternal mortality rates in developing countries are still unacceptably high as a result of high fertility and a high risk of dying each time a woman becomes pregnant. Complications of illegal abortion are responsible for 25-50% of maternal deaths. Safe contraception could probably result in an important reduction in the number of maternal deaths, but also the provision of accessible maternal health services is essential to reduce maternal mortality in developing countries.

To determine the effect of age and comorbid diseases on treatment choice and survival, the medical records of 300 breast cancer patients of 55 years and older were reviewed. All patients were admitted to the Netherlands Cancer Institute (NKI) for first treatment between 1980 and 1987. Patients were classified according to severity level of comorbid diseases. Physicians were found to treat women of 75 years and older less often with adjuvant radiotherapy after a mastectomy, and more often to employ only primary endocrine treatment for local stage disease, as compared with younger patients. According to the treatment guidelines of the institute, the study sample was divided into patients who received standard vs. non-standard treatment. The treatment of 38 women (13.1%) did not correspond with the guidelines. Of these, 84% were 75 years and older and 50% had a severe comorbidity status. Logistic regression analysis indicated that advanced age, per se, was a better indicator of the risk of not being treated according to protocol than the comorbidity status. Cox multivariate analyses demonstrated that neither the severity of the comorbidity status nor the differences in treatment between younger and older patients had a significant effect on the risk of dying from breast cancer or on the risk of developing recurrences. In this analysis, age 75 years or more proved to be a significant and independent predictor of a worse overall and disease-specific survival as compared to age between 65-74 years.

Plasma endothelin levels were studied in 29 pregnancies. Levels were found to be increased in 9 pregnancies complicated by pregnancy-induced hypertensive disease and/or pre-eclampsia as compared to levels in 14 normotensive pregnancies with gestational age varying between 24-40 weeks with normal Doppler flow velocity waveforms of the uterine arcuate arteries, and 6 normotensive pregnancies with abnormal Doppler flow velocity waveforms at 24 weeks' gestation. Two patients with severe pre-eclampsia showed a rise in plasma endothelin levels, suggesting a correlation between plasma endothelin levels and the disease process. Endothelin is produced by endothelial cells of blood vessels; it is the most potent vasoconstrictor known to date. For this reason it has been suggested that endothelin might be important in the control of systemic blood pressure and local blood flow, both disturbed in pre-eclampsia. The conclusion of this study is that the venous plasma level of endothelin would seem to be a marker for severe disease, however, without any predictive value.

The signs and symptoms of preeclampsia are usually apparent at a relatively late stage in pregnancy (late second to early third trimester). However, the disorder results from abnormal interaction between fetal and maternal tissue much earlier in pregnancy, between 8 and 18 weeks' gestation. During the past two decades numerous clinical, biophysical, and biochemical tests have been proposed for the early detection of preeclampsia. Some of these tests are simple, whereas others are invasive; some have been studied extensively, while others are still under clinical investigation. A review of the literature indicates considerable disagreement regarding the sensitivity and predictive values of the various tests studied. The reported differences in the predictive values of these tests may be attributed to one or more of the following: populations studied, definition and prevalence of the disorder, techniques and methodology used in performing these tests, etc. As a result, there is disagreement regarding the ideal screening test to be used for identifying patients for clinical trials dealing with prevention of the disorder.

The hypothesis that an enhanced vasopressor response to angiotensin II in pregnancy may be corrected by suppressing production of platelet thromboxane A2 with low-dose aspirin was tested in a randomized, placebo-controlled, double-blind trial. We studied 36 normotensive primigravid women with an elevated blood pressure response to intravenously infused angiotensin II at 28 weeks' gestation; 18 women received 60 mg of aspirin daily and the same number received matched placebo until 34 weeks' gestation, when angiotensin-sensitivity was again determined. In women taking aspirin, values of thrombin-induced platelet malondialdehyde production were approximately 10% of those determined in the placebo group, indicating marked suppression of thromboxane A2 synthesis. In the aspirin group vascular refractoriness to angiotensin II was restored in 14 of 17 treated women, by comparison with 5 of 15 women in the placebo group who had remained normotensive. These results support the hypothesis that prostacyclin/thromboxane imbalance is an important pathophysiologic factor in the development of the enhanced angiotensin-sensitivity associated with pregnancy-induced hypertensive disorders.

A 30-yr-old woman is described with an intermediate-grade non-Hodgkin's lymphoma, localized in the mediastinum, diagnosed in the 22nd week of gestation. Combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, prednisone, teniposide and bleomycin was instituted in the second and third trimesters, resulting in regression of the tumour. Foetal distress due to pre-eclampsia forced us to perform a Caesarean section at 31 weeks of pregnancy. A healthy boy was born without congenital abnormalities. Further chemotherapeutic treatment, combined with radiotherapy, led to a complete remission of the non-Hodgkin's lymphoma; the remission lasted for 6 months. A review of the literature on chemotherapeutic treatment in non-Hodgkin's lymphoma during gestation is provided. Despite the limited number of cases reported, it can be concluded that chemotherapy in non-Hodgkin's lymphoma during pregnancy is less harmful than might be thought.

An angiotensin II sensitivity test and a supine pressor test were done consecutively at 28 weeks gestation in 90 healthy, normotensive nulliparous women. None of the supine pressor tests was positive, applying the predefined threshold of a rise of 20 mmHg in diastolic blood pressure after rolling over; nine tests were positive using a corrected 9 mmHg cut-off level. Ten women had a positive angiotensin sensitivity test using a threshold of the effective pressor dose of 8 ng/kg/min; 22 women were positive using an effective pressor dose of less than or equal to 10 ng/kg/min. Later in pregnancy 12 women (13%) developed pregnancy-induced hypertensive disease (PIH). The specificity of both tests of predicting the development of PIH was about 90%. The sensitivity of the angiotensin sensitivity test at the 10 ng/kg/min level was 92%. Because of its low sensitivity of 25% the supine pressor test appears to have no value for the prediction of PIH. There was a significant positive association between angiotensin II refractoriness and birthweight.

The possibility of preventing pregnancy-induced hypertension (PIH) and pre-eclampsia in primigravidae by suppressing production of thromboxane A2 with low-dose aspirin was investigated in a randomised, placebo-controlled, double-blind trial. 46 normotensive women at 28 weeks' gestation, judged to be at risk of PIH or pre-eclampsia because of an increased blood-pressure response to intravenously infused angiotensin II, were studied. 23 women received 60 mg aspirin daily, and the same number received matching placebo until delivery. In the placebo group PIH, pre-eclampsia, and eclampsia developed in 4, 7, and 1 cases, respectively, whereas only 2 women in the aspirin group had mild PIH. There were no adverse effects of treatment in mothers or infants. Low-dose aspirin may restore prostacyclin/thromboxane imbalance, previously suggested as an important aetiological factor in PIH and pre-eclampsia.