This multicenter study examined the adherence of high-risk women to screening recommendations for breast and ovarian cancer following consultation at a familial cancer clinic (FCC). Self-report questionnaires assessing recall of screening advice, tests undertaken, risk perception, anxiety (Impact of Events Scale) and demographics were mailed to 396 consecutive eligible women who had attended one of six FCCs a median of 3.6 years prior. Family history, genetic test results and screening recommendations were abstracted from medical records. 182/266 (68.4%) women responded with 130 lost to follow-up. The proportions of women undertaking at least the recommended frequency of screening tests were: breast self examination (BSE) 50.4%, clinical breast examination (CBE) 66.0%, mammography 82.2%, transvaginal ultrasound (TVUS) 70.0%, CA125 84.0%. Factors associated with adherence to screening were: higher anxiety for BSE and CBE, being BRCA1/2 positive for CBE, older age, method of arrangement and having at least one affected first degree relative for mammography. Factors significantly associated with over-adherence were higher scores for anxiety for BSE and CBE and younger age (< 40 years) for TVUS. Between 41.3% (BSE) and 57.6% (CBE) of women incorrectly recalled their screening recommendations. A substantial minority of high-risk women do not adhere to screening advice. Strategies to improve the accuracy of recall of recommendations and the uptake of recommended screening are required.

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1. The role of the potent vasodilator nitric oxide in the pathogenesis of pre-eclampsia is unclear. We have tested the hypothesis that placental activity of the enzyme which synthesizes nitric oxide (nitric oxide synthase) is reduced in pre-eclampsia. 2. Placentae were obtained after vaginal delivery or Caesarean section from women who had been assigned to the following groups according to standard obstetric criteria: term non-pre-eclamptic control, term pre-eclamptic, preterm non-pre-eclamptic control and preterm pre-eclamptic. Nitric oxide synthase activity of placental tissue homogenates was assessed by measuring conversion of [3H]L-arginine into [3H]L-citrulline in the presence of NADPH, FAD, tetrahydrobiopterin, calmodulin, CaCl2, magnesium acetate and a range of L-arginine concentrations. Michaelis Menton constants (K(m)) amd maximum velocities of reaction (Vmax) were calculated using Lineweaver-Burk analysis. 3. Vmax was significantly reduced in both term and preterm pre-eclamptic placentae compared with placentae from corresponding gestation-matched controls. There were no significant differences in the K(m) values for nitric oxide synthase between any of the four groups, nor were Vmax or K(m) values significantly influenced by mode of delivery. 4. These results provide evidence that human placental nitric oxide synthase activity is significantly reduced in pre-eclampsia. Such a reduction was evident at both term and preterm gestations. Reduced placental nitric oxide synthase activity may have an adverse effect on placental haemodynamic function in pre-eclampsia, and could be involved in the pathogenesis of this important and common obstetric complication.

Factors affecting fetal vessel resistance have been studied in vitro in bilaterally perfused lobules of human placentae. Potent and efficacious constrictors in this preparation (in order of potency) include endothelin-1 > the thromboxane mimetic U46619 > endothelin-3 > prostaglandin F2 alpha. Inhibitors of eicosanoid synthesis did not affect fetal vessel basal perfusion pressure, nor did they potentiate the effects of the vasoconstrictor U46619. In contrast, the nitric oxide inhibitors N omega-nitro-L-arginine (NOLA), haemoglobin and methylene blue all increased fetal vessel basal perfusion pressure and also increased U46619-induced constriction. Similarly, NOLA markedly potentiated the constrictor effects of endothelin-1, angiotensin II, 5-hydroxytryptamine and bradykinin. These studies therefore provide evidence that NO is important in the maintenance of low basal fetal vessel impedance and also reduces the effects of a number of vasoconstrictor autacoids. Nitric oxide synthase (NOS) activity of human placental homogenates has been measured and shown to be mainly calcium-dependent. Human placental NOS activity was not affected by labour state but was reduced in pre-eclampsia. No evidence was found that in pre-eclampsia raised concentrations of the endogenous NOS inhibitor asymmetric dimethylarginine were responsible for the reduced placental NOS activity. Hence, these studies provide evidence that NO is an important endogenous dilator of the fetal vessels of the human placenta and that reduced NOS activity could contribute to the pathogenesis and/or effects of pre-eclampsia.

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